Miracle-dz/UniFAR-FTUs huggingface dataset:
Gender Differences in Chronic Obstructive Pulmonary Disease Symptom Clusters

Purpose Previous research has indicated that female and male patients may experience different levels of symptoms. However, no studies of chronic obstructive pulmonary disease (COPD) patients have compared the number and types of symptom clusters identified in male and female patients. Therefore, the purpose of this study was to investigate gender differences in symptom clusters among COPD patients. Patients and Methods A total of 371 eligible patients were enrolled in the study. We assessed nine COPD symptoms, namely, dyspnea, cough, sputum, chest tightness, sleep quality, fatigue, frailty, anxiety, and depression. Exploratory factor analyses were used to explore the underlying clusters of the COPD symptoms. Results Underlying the nine symptoms, female patients had 2 clusters, and male patients had 3 clusters. Specifically, the three general symptoms poor sleep, fatigue, and frailty loaded on the same symptom cluster with anxiety and depression in female patients, while the same 3 general symptoms loaded on the same symptom cluster with chest tightness and dyspnea in male patients. Moreover, cough and sputum not only were more common in male patients but also loaded together on a separate symptom cluster. Conclusion Our findings suggest that in order to improve fatigue, frailty, and poor sleep quality, symptom management strategies should more closely address anxiety and depression in female patients as well as chest tightness and dyspnea in male patients. Smoking cessation is particularly important in male COPD patients because they account for a much higher proportion of smokers and are more likely to have cough and sputum. These findings signify the importance of identifying and implementing gender-tailored symptom management strategies to relieve symptom burden in COPD patients to enhance their quality of life.
One-Year Evolution of Symptoms and Health Status of the COPD Multi-Dimensional Phenotypes: Results from the Follow-Up of the STORICO Observational Study

Aim: Describing the 1-year evolution of symptoms and health status in COPD patients enrolled in the STORICO study (observational study on characterization of 24-h symptoms in patients with COPD) classified in multidimensional phenotypes (m-phenotypes). Methods: In our previous study, we performed an exploratory factor analysis to identify clinical and pathophysiological variables having the greatest classificatory properties, fol-lowed by a cluster analysis to group patients into m-phenotypes (mild COPD (MC), mild emphysematous (ME), severe bronchitic (SB), severe emphysematous (SE), and severe mixed COPD (SMC)). COPD symptoms were recorded at baseline, 6-, and 12-month follow-up and their evolution was described as frequency of patients with always present, always absent, arising’, ‘no more present symptoms. QoL and quality of sleep were evaluated using the SGRQ and CASIS questionnaires, respectively. Results: We analyzed 379 subjects (144 MC, 71 ME, 96 SB, 14 SE, 54 SMC). M-phenotypes were stable over time in terms of presence of symptoms and health status with selected differences in evolution of symptoms in mild vs severe m-phenotypes. Indeed, 28.1% SB, 50.0% SE and 24.1% SMC vs 0.7% MC and 5.6% ME with night-time symptoms at baseline had no more symptoms at 6-month (p-value night-time symptom evolution MC vs SB, SE, SMC and ME vs SB, SE, SMC <0.0001). All m-phenotypes improved in quality of sleep, more markedly the severe than the mild ones (p-values CASIS score change between baseline and 6- or 12-month in MC, ME vs SB, SE, SMC <0.0001). QoL did not change during observation, irrespectively of m-phenotype. Conclusion: Over 1 year, severe m-phenotypes showed an improvement in night-time symptoms and quality of sleep, but not QoL. Being stable over time, m-phenotypes seem worthy of testing for classificatory and prognostic purposes. total lung capacity; MD, mild COPD; ME, mild emphysematous; SB, severe bronchitic; SE, severe emphysematous; SMC, severe mixed COPD. capacity for carbon monoxide; FEV1, forced expiratory the first second; HADS, Hospital Scale; ICS, inhaled corticosteroids; IQR, interquartile range; LABA, long-acting β2-agonists; LAMA, long-acting muscarinic agonists; MC, mild COPD; ME, mild emphysematous; mMRC, modified Medical Research Council; RV, residual volume; SB, severe bronchitic; SD, standard deviation; SE, severe emphysematous; SGRQ, St. George’s Respiratory SMC, severe mixed COPD; TLC, total lung capacity.
Lung Deposition and Inspiratory Flow Rate in Patients with Chronic Obstructive Pulmonary Disease Using Different Inhalation Devices: A Systematic Literature Review and Expert Opinion

Background Our aim was to describe: 1) lung deposition and inspiratory flow rate; 2) main characteristics of inhaler devices in chronic obstructive pulmonary disease (COPD). Methods A systematic literature review (SLR) was conducted to analyze the features and results of inhaler devices in COPD patients. These devices included pressurized metered-dose inhalers (pMDIs), dry powder inhalers (DPIs), and a soft mist inhaler (SMI). Inclusion and exclusion criteria were established, as well as search strategies (Medline, Embase, and the Cochrane Library up to April 2019). In vitro and in vivo studies were included. Two reviewers selected articles, collected and analyzed data independently. Narrative searches complemented the SLR. We discussed the results of the reviews in a nominal group meeting and agreed on various general principles and recommendations. Results The SLR included 71 articles, some were of low–moderate quality, and there was great variability regarding populations and outcomes. Lung deposition rates varied across devices: 8%–53% for pMDIs, 7%-69% for DPIs, and 39%–67% for the SMI. The aerosol exit velocity was high with pMDIs (more than 3 m/s), while it is much slower (0.84–0.72 m/s) with the SMI. In general, pMDIs produce large-sized particles (1.22–8 μm), DPIs produce medium-sized particles (1.8–4.8 µm), and 60% of the particles reach an aerodynamic diameter <5 μm with the SMI. All inhalation devices reach central and peripheral lung regions, but the SMI distribution pattern might be better compared with pMDIs. DPIs’ intrinsic resistance is higher than that of pMDIs and SMI, which are relatively similar and low. Depending on the DPI, the minimum flow inspiratory rate required was 30 L/min. pMDIs and SMI did not require a high inspiratory flow rate. Conclusion Lung deposition and inspiratory flow rate are key factors when selecting an inhalation device in COPD patients.
Depletion of hsa_circ_0000144 Suppresses Oxaliplatin Resistance of Gastric Cancer Cells by Regulating miR-502-5p/ADAM9 Axis

Background Circular RNAs (circRNAs) have been disclosed to exert important roles in human cancers, including gastric cancer (GC). CircRNA hsa_circ_0000144 was identified as an oncogene in GC development. The aim of our study was to explore the role of hsa_circ_0000144 in oxaliplatin (OXA) resistance of GC. Methods Expression levels of hsa_circ_0000144, microRNA-502-5p (miR-502-5p) and A disintegrin and metalloproteinase 9 (ADAM9) were examined by quantitative real-time PCR (RT-qPCR) or Western blot assay. The OXA resistance of GC cells was evaluated by Cell Counting Kit-8 (CCK-8) assay. Colony formation assay was performed to assess the colony formation capacity. Cell apoptosis was determined by flow cytometry and caspase 3 activity. And cell migration and invasion were detected by Transwell assay. Target association between miR-502-5p and hsa_circ_0000144 or ADAM9 was demonstrated by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Moreover, role of hsa_circ_0000144 in vivo was analyzed by xenograft tumor assay. Results Hsa_circ_0000144 and ADAM9 were highly expressed, while miR-502-5p was downregulated in OXA-resistant GC tissues and cells. Depletion of hsa_circ_0000144 could inhibit OXA resistance, proliferation and metastasis in OXA-resistant GC cells, which was attenuated by miR-502-5p inhibition. Hsa_circ_0000144 sponged miR-502-5p to positively regulate ADAM9 expression. MiR-502-5p suppressed OXA resistance, proliferation and metastasis in OXA-resistant GC cells by targeting ADAM9. Hsa_circ_0000144 knockdown could hamper tumor growth in vivo. Conclusion Hsa_circ_0000144 exerted inhibitory effects on OXA resistance, proliferation and metastasis of OXA-resistant GC cells by regulating miR-502-5p/ADAM9 axis, at least in part.
Exploiting D2 receptor β‐arrestin2‐biased signalling to suppress tumour growth of pituitary adenomas

Dopamine agonists targeting D2 receptor have been used for decades in treating pituitary adenomas. There has been little clear evidence implicating the canonical G protein signalling as the mechanism by which D2 receptor suppresses the growth of pituitary tumours. We hypothesize that β‐arrestin2‐dependent signalling is the molecular mechanism dictating D2 receptor inhibitory effects on pituitary tumour growth.
Stereotactic body radiotherapy for oligoprogressive lesions in metastatic castration‐resistant prostate cancer patients during abiraterone/enzalutamide treatment

Metastasis‐directed therapy (MDT) utilizing stereotactic body radiotherapy (SBRT) for oligoprogressive lesions could provide a delay in next‐line systemic treatment (NEST) change while undergoing androgen receptor‐targeted agents (ARTA) treatment. We evaluated prognostic factors for prostate cancer‐specific survival (PCSS) and progression‐free survival (PFS) to characterize patients receiving treatment with ARTA who may benefit from MDT for oligoprogressive lesions. The impact of MDT on delaying NEST and the predictive factors for NEST‐free survival (NEST‐FS) were also assessed.
Multiscale photonic imaging of the native and implanted cochlea

Significance For the development of gene therapy and optical cochlear implants (oCI), detailed knowledge of the cochlear morphology is crucial. Here, we employed multiscale X-ray and fluorescence imaging for quantitative assessment of scala tympani, vestibuli, and media, as well as the spiral ganglion in Rosenthal’s canal for various species commonly used in auditory research. Furthermore, we demonstrate the feasibility of oCI implantation for rodents and marmosets, as a nonhuman primate model. Using modeling of light propagation from the emitters of the oCI, we estimate the frequency selectivity and range covered by optical stimulation within the cochlea. The cochlea of our auditory system is an intricate structure deeply embedded in the temporal bone. Compared with other sensory organs such as the eye, the cochlea has remained poorly accessible for investigation, for example, by imaging. This limitation also concerns the further development of technology for restoring hearing in the case of cochlear dysfunction, which requires quantitative information on spatial dimensions and the sensorineural status of the cochlea. Here, we employed X-ray phase-contrast tomography and light-sheet fluorescence microscopy and their combination for multiscale and multimodal imaging of cochlear morphology in species that serve as established animal models for auditory research. We provide a systematic reference for morphological parameters relevant for cochlear implant development for rodent and nonhuman primate models. We simulate the spread of light from the emitters of the optical implants within the reconstructed nonhuman primate cochlea, which indicates a spatially narrow optogenetic excitation of spiral ganglion neurons.
Is there a single beta oscillation band interfering with movement in Parkinson's disease?

Beta oscillations in basal ganglia are considered to contribute to motor dysfunction in Parkinson's disease (PD). However, there is a high variety in frequency borders for beta oscillations between studies, which complicates the comparison and interpretation of results. Here we aimed to study the homogeneity of oscillations in the broad “beta” range (8–30 Hz) and their implication to motor functioning in PD. For this purpose, we recorded local field potentials (LFP) in the subthalamic nucleus (STN) during 34 deep brain stimulation surgeries. We identified spectral features of LFP recordings in the range 8–30 Hz to search for candidate sub‐regions of stable oscillations and assessed their association with clinical scores on the contralateral side of the body and sensitivity to motor tests. Lower frequency oscillations (8–16 Hz) had a significant positive association with bradykinesia score. During voluntary movements, we observed a significant increase in LFP power in the 12–16 Hz range and a decrease in the 18–26 Hz range. We may conclude that the 8–30 Hz oscillation range includes oscillations with different functional features—sensitivity and responsiveness to movement, and clinical symptoms, which should be taken into account in further studies of beta oscillations association with PD pathophysiology. These data assume the coexistence of several frequency domains within beta range that are modulated in different ways under dopaminergic regulation and motor processing in human STN.
Semen evaluation: methodological advancements in sperm quality-specific fertility assessment — A review

Assessment of male fertility is based on the evaluation of sperm. Semen evaluation measures various sperm quality parameters as fertility indicators. However, semen evaluation has limitations, and it requires the advancement and application of strict quality control methods to interpret the results. This article reviews the recent advances in evaluating various sperm-specific quality characteristics and methodologies, with the help of different assays to assess sperm-fertility status. Sperm evaluation methods that include conventional microscopic methods, computer-assisted sperm analyzers (CASA), and flow cytometric analysis, provide precise information related to sperm morphology and function. Moreover, profiling fertility-related biomarkers in sperm or seminal plasma can be helpful in predicting fertility. Identification of different sperm proteins and diagnosis of DNA damage has positively contributed to the existing pool of knowledge about sperm physiology and molecular anomalies associated with different infertility issues in males. Advances in methods and sperm-specific evaluation has subsequently resulted in a better understanding of sperm biology that has improved the diagnosis and clinical management of male factor infertility. Accurate sperm evaluation is of paramount importance in the application of artificial insemination and assisted reproductive technology. However, no single test can precisely determine fertility; the selection of an appropriate test or a set of tests and parameters is required to accurately determine the fertility of specific animal species. Therefore, a need to further calibrate the CASA and advance the gene expression tests is recommended for faster and field-level applications.
Transport of super-thermal particles and their effect on the stability of global modes in fusion plasmas

In thermonuclear plasmas, a population of super-thermal particles generated by external heating methods or fusion reactions can lead to the excitation of global instabilities. Nonlinear wave-particle interactions cause transport processes and consequential particle losses. The underlying mechanisms were studied with a numerical model, and experimental findings could be explained theoretically.
Solid Organ Transplantation From Deceased Donors With Infective Endocarditis: The UK Experience

Background. There is little evidence regarding the use of organs from deceased donors with infective endocarditis. We performed a retrospective analysis of the utilization, safety, and long-term survival of transplants from donors with infective endocarditis in the United Kingdom. Methods. We studied deceased donor transplants over an 18-y period (2001–2018) using data from the UK Transplant Registry. We estimated the risk of infection transmission, defined as a microbiological isolate in the recipient matching the causative organism in the donor in the first 30 days posttransplant. We examined all-cause allograft failure up to 5 years in kidney and liver recipients, comparing transplants from donors with endocarditis with randomly selected matched control transplants. Results. We studied 88 transplants from 42 donors with infective endocarditis. We found no cases of infection transmission. There was no difference in allograft failure between transplants from donors with infective endocarditis and matched control transplants, among either kidney (hazard ratio, 1.48; 95% CI, 0.66-3.34) or liver (hazard ratio, 1.14; 95% CI, 0.54-2.41) recipients. Compared with matched controls, donors with infective endocarditis donated fewer organs (2.3 versus 3.2 organs per donor; P < 0.001) and were less likely to become kidney donors (odds ratio, 0.29; 95% CI, 0.16-0.55). Conclusions. We found acceptable safety and long-term allograft survival in transplants from selected donors with infective endocarditis in the United Kingdom. This may have implications for donor selection and organ utilization.
Medical education and distrust modulate the response of insular-cingulate network and ventral striatum in pain diagnosis

Healthcare providers often underestimate patients’ pain, sometimes even when aware of their reports. This could be the effect of experience reducing sensitivity to others pain, or distrust toward patients’ self-evaluations. Across multiple experiments (375 participants), we tested whether senior medical students differed from younger colleagues and lay controls in the way they assess people’s pain and take into consideration their feedback. We found that medical training affected the sensitivity to pain faces, an effect shown by the lower ratings and highlighted by a decrease in neural response of the insula and cingulate cortex. Instead, distrust toward the expressions’ authenticity affected the processing of feedbacks, by decreasing activity in the ventral striatum whenever patients’ self-reports matched participants’ evaluations, and by promoting strong reliance on the opinion of other doctors. Overall, our study underscores the multiple processes which might influence the evaluation of others’ pain at the early stages of medical career.
Optimal RNA binding by Egalitarian, a Dynein cargo adaptor, is critical for maintaining oocyte fate in Drosophila

ABSTRACT The Dynein motor is responsible for the localization of numerous mRNAs within Drosophila oocytes and embryos. The RNA binding protein, Egalitarian (Egl), is thought to link these various RNA cargoes with Dynein. Although numerous studies have shown that Egl is able to specifically associate with these RNAs, the nature of these interactions has remained elusive. Egl contains a central RNA binding domain that shares limited homology with an exonuclease, yet Egl binds to RNA without degrading it. Mutations have been identified within Egl that disrupt its association with its protein interaction partners, BicaudalD (BicD) and Dynein light chain (Dlc), but no mutants have been described that are specifically defective for RNA binding. In this report, we identified a series of positively charged residues within Egl that are required for RNA binding. Using corresponding RNA binding mutants, we demonstrate that specific RNA cargoes are more reliant on maximal Egl RNA biding activity for their correct localization in comparison to others. We also demonstrate that specification and maintenance of oocyte fate requires maximal Egl RNA binding activity. Even a subtle reduction in Egl’s RNA binding activity completely disrupts this process. Our results show that efficient RNA localization at the earliest stages of oogenesis is required for specification of the oocyte and restriction of meiosis to a single cell.
Exploring the GLP-1–GLP-1R axis in porcine pancreas and gastrointestinal tract in vivo by ex vivo autoradiography

Introduction Glucagon-like peptide-1 (GLP-1) increases insulin secretion from pancreatic beta-cells and GLP-1 receptor (GLP-1R) agonists are widely used as treatment for type 2 diabetes mellitus. Studying occupancy of the GLP-1R in various tissues is challenging due to lack of quantitative, repeatable assessments of GLP-1R density. The present study aimed to describe the quantitative distribution of GLP-1Rs and occupancy by endogenous GLP-1 during oral glucose tolerance test (OGTT) in pigs, a species that is used in biomedical research to model humans. Research design and methods GLP-1R distribution and occupancy were measured in pancreas and gastrointestinal tract by ex vivo autoradiography using the GLP-1R-specific radioligand 177Lu-exendin-4 in two groups of pigs, control or bottle-fed an oral glucose load. Positron emission tomography (PET) data from pigs injected with 68Ga-exendin-4 in a previous study were used to retrieve data on biodistribution of GLP-1R in the gastrointestinal tract. Results High homogenous uptake of 177Lu-exendin-4 was found in pancreas, and even higher uptake in areas of duodenum. Low uptake of 177Lu-exendin-4 was found in stomach, jejunum, ileum and colon. During OGTT, there was no increase in plasma GLP-1 concentrations and occupancy of GLP-1Rs was low. The ex vivo autoradiography results were highly consistent with to the biodistribution of 68Ga-exendin-4 in pigs scanned by PET. Conclusion We identified areas with similarities as well as important differences regarding GLP-1R distribution and occupancy in pigs compared with humans. First, there was strong ligand binding in the exocrine pancreas in islets. Second, GLP-1 secretion during OGTT is minimal and GLP-1 might not be an important incretin in pigs under physiological conditions. These findings offer new insights on the relevance of porcine diabetes models.
The role of long noncoding RNAs in livestock adipose tissue deposition — A review

With the development of sequencing technology, numerous, long noncoding RNAs (lncRNAs) have been discovered and annotated. Increasing evidence has shown that lncRNAs play an essential role in regulating many biological and pathological processes, especially in cancer. However, there have been few studies on the roles of lncRNAs in livestock production. In animal products, meat quality and lean percentage are vital economic traits closely related to adipose tissue deposition. However, adipose tissue accumulation is also a pivotal contributor to obesity, diabetes, atherosclerosis, and many other diseases, as demonstrated by human studies. In livestock production, the mechanism by which lncRNAs regulate adipose tissue deposition is still unclear. In addition, the phenomenon that different animal species have different adipose tissue accumulation abilities is not well understood. In this review, we summarize the characteristics of lncRNAs and their four functional archetypes and review the current knowledge about lncRNA functions in adipose tissue deposition in livestock species. This review could provide theoretical significance to explore the functional mechanisms of lncRNAs in adipose tissue accumulation in animals.