Miracle-dz/UniFAR-FTUs huggingface dataset:
The IASP classification of chronic pain for ICD-11: chronic primary pain

Abstract This article describes a proposal for the new diagnosis of chronic primary pain (CPP) in ICD-11. Chronic primary pain is chosen when pain has persisted for more than 3 months and is associated with significant emotional distress and/or functional disability, and the pain is not better accounted for by another condition. As with all pain, the article assumes a biopsychosocial framework for understanding CPP, which means all subtypes of the diagnosis are considered to be multifactorial in nature, with biological, psychological, and social factors contributing to each. Unlike the perspectives found in DSM-5 and ICD-10, the diagnosis of CPP is considered to be appropriate independently of identified biological or psychological contributors, unless another diagnosis would better account for the presenting symptoms. Such other diagnoses are called “chronic secondary pain” where pain may at least initially be conceived as a symptom secondary to an underlying disease. The goal here is to create a classification that is useful in both primary care and specialized pain management settings for the development of individualized management plans, and to assist both clinicians and researchers by providing a more accurate description of each diagnostic category.
Elevated S100A4 in asthmatics and an allergen‐induced mouse asthma model

The elevated S100A4 level has been found in some inflammatory diseases. However, the expression and role of S100A4 in asthma is unknown. The expression of S100A4 in induced sputum and plasma from healthy control and asthmatics were assessed by ELISA. Then an allergen‐induced asthma mouse model treatment with anti‐S100A4 antibody was used to explore the role of S100A4 in the pathogenesis of asthma. The S100A4 levels in sputum not in plasma in asthmatics were significantly increased than those of healthy controls and were negatively correlated with some lung function parameters and were positively correlated with sputum eosinophilia and lymphocyte. The expression of S100A4 in the lung as well as in BALF were also significantly higher in the asthma mouse model and treatment with anti‐S100A4 antibody exhibited reductions in inflammatory cell accumulation, inflammatory mediators, and airway hyper‐responsiveness. We further showed that LY294002, a specific inhibitor of PI3K, markedly decreased S100A4 expression in lung and S100A4 secretion in BALF in asthmatic mice. In conclusion, these data demonstrated that S100A4 may be involved in the pathogenesis of airway inflammation in asthma.
Electrophysiological abnormalities in induced pluripotent stem cell‐derived cardiomyocytes generated from Duchenne muscular dystrophy patients

Duchenne muscular dystrophy (DMD) is an X‐linked progressive muscle degenerative disease, caused by mutations in the dystrophin gene and resulting in death because of respiratory or cardiac failure. To investigate the cardiac cellular manifestation of DMD, we generated induced pluripotent stem cells (iPSCs) and iPSC‐derived cardiomyocytes (iPSC‐CMs) from two DMD patients: a male and female manifesting heterozygous carrier. Dystrophin mRNA and protein expression were analysed by qRT‐PCR, RNAseq, Western blot and immunofluorescence staining. For comprehensive electrophysiological analysis, current and voltage clamp were used to record transmembrane action potentials and ion currents, respectively. Microelectrode array was used to record extracellular electrograms. X‐inactive specific transcript (XIST) and dystrophin expression analyses revealed that female iPSCs underwent X chromosome reactivation (XCR) or erosion of X chromosome inactivation, which was maintained in female iPSC‐CMs displaying mixed X chromosome expression of wild type (WT) and mutated alleles. Both DMD female and male iPSC‐CMs presented low spontaneous firing rate, arrhythmias and prolonged action potential duration. DMD female iPSC‐CMs displayed increased beat rate variability (BRV). DMD male iPSC‐CMs manifested decreased If density, and DMD female and male iPSC‐CMs showed increased ICa,L density. Our findings demonstrate cellular mechanisms underlying electrophysiological abnormalities and cardiac arrhythmias in DMD.
A phase I study of cabozantinib plus nivolumab (CaboNivo) and ipilimumab (CaboNivoIpi) in patients (pts) with refractory metastatic urothelial carcinoma (mUC) and other genitourinary (GU) tumors.

293Background: We report the safety and clinical activity of CaboNivo and CaboNivoIpi in pts with mUC and other GU tumors. Methods: Part I included 4 dose levels (DLs) (Cabo PO daily and Nivo IV q2wk): DL1 Cabo40/Nivo1, DL2 Cabo40/Nivo3, DL3 Cabo60/Nivo1, DL4 Cabo 60/Nivo3. Part II included 3 DLs (Cabo PO daily, plus NivoIpi IV q3 wk x 4 doses then Nivo q2wk): DL5 Cabo 40/Nivo1/Ipi1, DL6 Cabo40/Nivo3/Ipi1, DL7 Cabo 60/Nivo3/Ipi 1. Tumors were assessed for overall response rate (ORR) by RECIST 1.1. Adverse events (AEs) were graded (G) by NCI-CTCAE v4.0. Results: From 7/22/15-10/14/16, 40pts [mUC N=14/(plasmacytoid N=1); bladder urachal N=4; bladder squamous cell carcinoma (bSCC) N=2; germ cell tumor (GCT) N=4; castrate-resistant prostate cancer (CRPC) N=9/(neuroendocrine prostate N=1); sarcomatoid renal cell carcinoma (sRCC) N=1; trophoblastic tumor N=1); sertoli cell tumor N=1; and penile SCC N=4] were treated. Median age was 58 (range 31-77); 36 (90%) were male. AEs related to study drugs with [1] CaboNi.
A Noisy Analog-to-Digital Converter Connects Cytosolic Calcium Bursts to Transcription Factor Nuclear Localization Pulses in Yeast

Several examples of transcription factors that show stochastic, unsynchronized pulses of nuclear localization have been described. Here we show that under constant calcium stress, nuclear localization pulses of the transcription factor Crz1 follow stochastic variations in cytosolic calcium concentration. We find that the size of the stochastic calcium bursts is positively correlated with the number of subsequent Crz1 pulses. Based on our observations, we propose a simple stochastic model of how the signaling pathway converts a constant external calcium concentration into a digital number of Crz1 pulses in the nucleus, due to the time delay from nuclear transport and the stochastic decoherence of individual Crz1 molecule dynamics. We find support for several additional predictions of the model and suggest that stochastic input to nuclear transport may produce noisy digital responses to analog signals in other signaling systems.
Time-Varying Respiratory Mechanics as a Novel Mechanism Behind Frequency Dependence of Impedance: A Modeling Approach

Frequency dependence of respiratory mechanics is a well-established behavior of the respiratory system and is known to be an indicator of severity of obstructive disease, attributed to both tissue viscoelasticity and heterogeneity of airflow in the lung. Despite the fact that respiratory parameters are known to vary in time, often amplified in disease, all analysis methods assume stationarity or short-time stationarity in the parameters used to describe the respiratory system, and the effects of this assumption have not yet been examined in any detail. Here, using a generalized approach, we developed a theory for time-varying respiratory mechanics in time-frequency domain for analysis of linear time-varying systems, then, we analyzed the same respiratory system model with time-varying parameters in the time domain. Both time-frequency domain and time-domain derivations revealed a striking correlation between time-varying behavior of the respiratory system and frequency dependence of resistance. Remarkably, this phenomenon arose from the amplitude of time variations of the elastance. This links two mechanisms that are known to increase in obstructive disease: apparent low frequency increases in resistance and the time variations of reactance.
Addressing Racial Inequities in Breastfeeding in the Southern United States

The CHAMPS project was used to address racial inequities in breastfeeding in the Southern United States by implementing practice changes based on the Ten Steps to Successful Breastfeeding. BACKGROUND: Race is a predictor of breastfeeding rates in the United States, and rates are lowest among African American infants. Few studies have assessed changes in breastfeeding rates by race after implementing the Ten Steps to Successful Breastfeeding (hereafter referred to as the Ten Steps), and none have assessed the association between implementation and changes in racial disparities in breastfeeding rates. Our goal was to determine if a hospital- and community-based initiative in the Southern United States could increase compliance with the Ten Steps, lead to Baby-Friendly designation, and decrease racial disparities in breastfeeding. METHODS: Hospitals in Mississippi, Louisiana, Tennessee, and Texas were enrolled into the Communities and Hospitals Advancing Maternity Practices initiative from 2014 to 2017 and received an intensive quality improvement and technical assistance intervention to improve compliance with the Ten Steps. Community partners and statewide organizations provided parallel support. Hospitals submitted monthly aggregate data stratified by race on breastfeeding, skin-to-skin care, and rooming in practices. RESULTS: The disparity in breastfeeding initiation between African American and white infants decreased by 9.6 percentage points (95% confidence interval 1.6–19.5) over the course of 31 months. Breastfeeding initiation increased from 66% to 75% for all races combined, and exclusivity increased from 34% to 39%. Initiation and exclusive breastfeeding among African American infants increased from 46% to 63% (P < .05) and from 19% to 31% (P < .05), respectively. Skin-to-skin care after cesarean delivery was significantly associated with increased breastfeeding initiation and exclusivity in all races; rooming in was significantly associated with increased exclusive breastfeeding in African American infants only. CONCLUSIONS: Increased compliance with the Ten Steps was associated with a decrease in racial disparities in breastfeeding.
Effect of immediate versus delayed loadings of dental implants on the oral health-related quality of life in Saudi population

Objectives: To assess the effects of immediate and delayed loadings of dental implants on the overall quality of life (QoL) of patients. Methods: The prospective analysis was conducted in the Department of Periodontology Clinics, Faculty of Dentistry Hospital, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia. The study was conducted from November 2013 to August 2016 and was according to the principles of the Helsinki Declaration. Quality of life in 24 patients (10 males and 14 females), aged between 18-60 years were assessed. Among the patients, 8 were opted for immediate implant loading (Group I), while 16 have opted for delayed implant loading (Group II). The quality of life was analyzed using a QoL assessment scale before and after the implant loading. Results: Overall assessment revealed that the QoL among the patients immediately after loading of dental implant (Group I) was better as compared to the delayed loading of dental implant (Group II). The differences of functional and financial aspects were significant between both groups. The majority of the immediate implant’s loadings have been performed in the anterior aesthetic zone and has a significant impact on the QoL. Conclusion: The results concluded that immediate loading of dental implant is better than the delayed loading of a dental implant with a prosthesis.
A functional MRI investigation of crossmodal interference in an audiovisual Stroop task

The visual color-word Stroop task is widely used in clinical and research settings as a measure of cognitive control. Numerous neuroimaging studies have used color-word Stroop tasks to investigate the neural resources supporting cognitive control, but to our knowledge all have used unimodal (typically visual) Stroop paradigms. Thus, it is possible that this classic measure of cognitive control is not capturing the resources involved in multisensory cognitive control. The audiovisual integration and crossmodal correspondence literatures identify regions sensitive to congruency of auditory and visual stimuli, but it is unclear how these regions relate to the unimodal cognitive control literature. In this study we aimed to identify brain regions engaged by crossmodal cognitive control during an audiovisual color-word Stroop task, and how they relate to previous unimodal Stroop and audiovisual integration findings. First, we replicated previous behavioral audiovisual Stroop findings in an fMRI-adapted audiovisual Stroop paradigm: incongruent visual information increased reaction time towards an auditory stimulus and congruent visual information decreased reaction time. Second, we investigated the brain regions supporting cognitive control during an audiovisual color-word Stroop task using fMRI. Similar to unimodal cognitive control tasks, a left superior parietal region exhibited an interference effect of visual information on the auditory stimulus. This superior parietal region was also identified using a standard audiovisual integration localizing procedure, indicating that audiovisual integration resources are sensitive to cognitive control demands. Facilitation of the auditory stimulus by congruent visual information was found in posterior superior temporal cortex, including in the posterior STS which has been found to support audiovisual integration. The dorsal anterior cingulate cortex, often implicated in unimodal Stroop tasks, was not modulated by the audiovisual Stroop task. Overall the findings indicate that an audiovisual color-word Stroop task engages overlapping resources with audiovisual integration and overlapping but distinct resources compared to unimodal Stroop tasks.
Medicinal Plants Used in the Ejisu-Juaben Municipality, Southern Ghana: An Ethnobotanical Study

Background: The in-depth traditional knowledge of medicinal plants is at risk of extinction due to the dependency on oral transmission, and as such, there is an urgent need to document such knowledge. This study aimed to document indigenous uses of medicinal plants among community members in the Ejisu-Juaben Municipality. Methods: Data was collected in 2016 from community members and local herbalists in the Ejisu-Juaben Municipality through a semi-structured questionnaire. Statistical tools and ethnobotanical indices, i.e., informant consensus factor (ICF), fidelity level (FL), and use value (UV) were used to analyse the data. Results: One hundred and six medicinal plants belonging to 45 families were reported to cure 68 different human diseases. The most frequently used plant part in this study was the leaves (52%). Decoction (57.5%) and oral administration (58.3%) were the most utilised herbal preparation and administration route respectively. Cleistopholis patens had the highest UV (0.54) with pain & fevers and skin diseases having the highest ICF values (0.88 and 0.85 respectively). Furthermore, new medicinal uses of Hilleria latifolia and ten other species were recorded for the treatment of the traditional local disease, aseram. Conclusions: The current knowledge and uses of medicinal plants are still high in the study area based on the high degree of consensus among informants. This study could allow for the preservation of knowledge and biodiversity of medicinal plants, both of which are threatened with extinction.
Robust clinical marker identification for diabetic kidney disease with ensemble feature selection

Objective Diabetic kidney disease (DKD) is one of the most frequent complications in diabetes associated with substantial morbidity and mortality. To accelerate DKD risk factor discovery, we present an ensemble feature selection approach to identify a robust set of discriminant factors using electronic medical records (EMRs). Material and Methods We identified a retrospective cohort of 15 645 adult patients with type 2 diabetes, excluding those with pre-existing kidney disease, and utilized all available clinical data types in modeling. We compared 3 machine-learning-based embedded feature selection methods in conjunction with 6 feature ensemble techniques for selecting top-ranked features in terms of robustness to data perturbations and predictability for DKD onset. Results The gradient boosting machine (GBM) with weighted mean rank feature ensemble technique achieved the best performance with an AUC of 0.82 [95%-CI, 0.81-0.83] on internal validation and 0.71 [95%-CI, 0.68-0.73] on external temporal validation. The ensemble model identified a set of 440 features from 84 872 unique clinical features that are both predicative of DKD onset and robust against data perturbations, including 191 labs, 51 visit details (mainly vital signs), 39 medications, 34 orders, 30 diagnoses, and 95 other clinical features. Discussion Many of the top-ranked features have not been included in the state-of-art DKD prediction models, but their relationships with kidney function have been suggested in existing literature. Conclusion Our ensemble feature selection framework provides an option for identifying a robust and parsimonious feature set unbiasedly from EMR data, which effectively aids in knowledge discovery for DKD risk factors.
Dietary Patterns in Relation to Low Bone Mineral Density and Fracture Risk: A Systematic Review and Meta-Analysis.

Low bone mineral density (BMD) and osteoporosis-related fractures constitute a considerable public health burden. Several studies have demonstrated the association between diet and bone health. We performed a systematic review to provide an estimate of the association between different dietary patterns defined through the use of a posteriori methods and fracture or low BMD risk. A literature search on PubMed, Web of Science, and Scopus databases, up to March 2018, was performed to identify all eligible case-control, prospective, or cross-sectional studies involving subjects of both sexes and any age. Random-effects models were used. Heterogeneity and publication bias were evaluated. Stratified analyses were conducted on study characteristics. The meta-analysis includes 20 studies and identifies 3 prevalent dietary patterns: "Healthy," "Milk/dairy," and "Meat/Western. " From the 10 studies on fracture, adherence to the "Healthy" pattern reduced the risk, particularly in older people (OR: 0.79; 95% CI: 0.66, 0.95; P = 0.011) and in Eastern countries (OR: 0.64; 95% CI: 0.43, 0.97; P = 0.037), whereas the risk increased with the "Meat/Western" pattern, especially for older people (OR: 1.11; 95% CI: 1.04, 1.18, P = 0.001), in those with hip fractures (OR: 1.15; 95% CI: 1.05, 1.25; P = 0.002), and in Western countries (OR: 1.10; 95% CI: 1.07, 1.14; P < 0.0001). Analyses on low BMD showed a reduced risk in the "Healthy" pattern, particularly for younger people (OR: 0.62; 95% CI: 0.44, 0.89; P = 0.009). The "Meat/Western" pattern increased low BMD risk, especially in older people (OR: 1.31; 95% CI: 1.05, 1.64; P = 0.015). The "Milk/dairy" pattern resulted in the strongest reduction in low BMD risk; when stratifying, this effect remained significant (e.g., older women-OR: 0.57; 95% CI: 0.46, 0.70; P < 0.0001). Nutrition is an important modifiable factor affecting bone health. The "Healthy" and "Milk/dairy" patterns are associated with a reduced risk of low BMD and fracture. In contrast, the "Western" pattern is inversely associated.
Bioactive cell-like hybrids from dendrimersomes with a human cell membrane and its components

Significance Gram-negative bacterial cells such as Escherichia coli contain a relatively rigid outer membrane, and cross-linked peptidoglycan in their periplasm, giving them the rigidity and stability to survive independently in harsh environments. To dismantle these strong bacterial cell envelopes, enzymatic processes need to be used. In contrast, human cell membranes are much more fragile, making it possible to dismantle them more easily by relatively mild mechanical disruption. Once these membranes are dismantled, they can be coassembled with synthetic phospholipid mimics, named Janus dendrimers, into cell-like hybrids. This method stabilizes the delicate human cell membranes, introducing the potential for the study of human cell membranes and of their constituents in vitro in a more robust environment. Cell-like hybrids from natural and synthetic amphiphiles provide a platform to engineer functions of synthetic cells and protocells. Cell membranes and vesicles prepared from human cell membranes are relatively unstable in vitro and therefore are difficult to study. The thicknesses of biological membranes and vesicles self-assembled from amphiphilic Janus dendrimers, known as dendrimersomes, are comparable. This feature facilitated the coassembly of functional cell-like hybrid vesicles from giant dendrimersomes and bacterial membrane vesicles generated from the very stable bacterial Escherichia coli cell after enzymatic degradation of its outer membrane. Human cells are fragile and require only mild centrifugation to be dismantled and subsequently reconstituted into vesicles. Here we report the coassembly of human membrane vesicles with dendrimersomes. The resulting giant hybrid vesicles containing human cell membranes, their components, and Janus dendrimers are stable for at least 1 y. To demonstrate the utility of cell-like hybrid vesicles, hybrids from dendrimersomes and bacterial membrane vesicles containing YadA, a bacterial adhesin protein, were prepared. The latter cell-like hybrids were recognized by human cells, allowing for adhesion and entry of the hybrid bacterial vesicles into human cells in vitro.
A comparison of sufentanil vs. remifentanil in fast‐track cardiac surgery patients†

We retrospectively compared patients receiving remifentanil with patients receiving sufentanil undergoing fast‐track cardiac surgery. After 1:1 propensity score matching there were 609 patients in each group. The sufentanil group had a significantly longer mean (SD) ventilation time compared with the remifentanil group; 122 (59) vs. 80 (44) min, p < 0.001 and longer mean (SD) length of stay in the recovery area; 277 (77) vs. 263 (78) min, p = 0.002. The sufentanil group had a lower mean (SD) visual analogue pain score than the remifentanil group; 1.5 (1.2) vs. 2.4 (1.5), p < 0.001 and consumed less mean (SD) piritramide (an opioid analgesic used in our hospital); 2.6 (4.7) vs. 18.9 (7.3) mg, p < 0.001. The results of our study show that although remifentanil was more effective in reducing time to tracheal extubation and length of stay in the recovery area, there was an increased requirement for postoperative analgesia when remifentanil was used.