Miracle-dz/UniFAR-FTUs huggingface dataset:
Upregulation of long non-coding RNA MYU promotes proliferation, migration and invasion of esophageal squamous cell carcinoma cells

Esophageal squamous cell carcinoma (ESCC) is a common malignant tumour type of the digestive system. Long non-coding RNA (lncRNA) c-Myc upregulated (MYU), also known as VPS9 domain-containing 1 antisense 1, was recently discovered. However, the expression of lncRNA MYU in ESCC and its role in tumour progression have remained elusive. In the present study, the expression of lncRNA MYU, Ki-67 and the epithelial-mesenchymal transition-related proteins E-cadherin and Vimentin in ESCC tissues was detected by reverse transcription-quantitative PCR. The expression of Ki-67, E-cadherin and Vimentin in ESCC tissues was also detected by immunohistochemistry. A small interfering RNA plasmid was employed to establish a TE-2 cell line with knockdown on lncRNA MYU. The results indicated that the expression of lncRNA MYU was higher in ESCC tissues than in normal adjacent tissues and that upregulation of lncRNA MYU was a potential biomarker for poor prognosis. The results also suggested that the expression levels of lncRNA MYU were correlated with the histological grade, lymph node metastasis and TNM stage (P<0.05). Silencing of lncRNA MYU expression inhibited the proliferation, migration and invasion, while the expression of lncRNA MYU increased as cell proliferation increased. In addition, the mRNA expression of Vimentin and Ki-67 was decreased in TE-2 cells after lncRNA MYU was knocked down, while E-cadherin mRNA expression was elevated. In conclusion, the present results indicated that lncRNA MYU may regulate the proliferation, migration and invasion of ESCC cells, and may serve as a prognostic biomarker for ESCC.
Regulatory mechanism of calcium/calmodulin-dependent protein kinase II in the occurrence and development of ventricular arrhythmia (Review)

Ventricular arrhythmia (VA) is a highly fatal arrhythmia that involves multiple ion channels. Of all sudden cardiac death events, ~85% result from VAs, including ventricular tachycardia and ventricular fibrillation. Calcium/calmodulin-dependent pro-tein kinase II (CaMKII) is an important ion channel regulator that participates in the excitation-contraction coupling of the heart, and as such is important for regulating its electrophysiological function. CaMKII can be activated in a Ca2+/calmodulin (CaM)-dependent or Ca2+/CaM-independent manner, serving a key role in the occurrence and development of VA. The present review aimed to determine whether activated CaMKII induces early afterdepolarizations and delayed afterdepolarizations that result in VA by regulating sodium, potassium and calcium ions. Assessing VA mechanisms based on the CaMKII pathway is of great significance to the clinical treatment of VA and the de-velopment of effective drugs for use in clinical practice.
Insights From the SmokeFree.gov Initiative Regarding the Use of Smoking Cessation Digital Platforms During the COVID-19 Pandemic: Cross-sectional Trends Analysis Study

Background Smoking is a plausible risk factor for COVID-19 progression and complications. Smoking cessation digital platforms transcend pandemic-driven social distancing and lockdown measures in terms of assisting smokers in their quit attempts. Objective This study aims to examine trends in the number of visitors, followers, and subscribers on smoking cessation digital platforms from January to April 2020 and to compare these traffic data to those observed during the same 4-month period in 2019. The examination of prepandemic and postpandemic trends in smoking cessation digital platform traffic can reveal whether interest in smoking cessation among smokers is attributable to the COVID-19 pandemic. Methods We obtained cross-sectional data from daily visitors on the SmokeFree website; the followers of six SmokeFree social media accounts; and subscribers to the SmokeFree SMS text messaging and mobile app interventions of the National Cancer Institute’s SmokeFree.gov initiative platforms, which are publicly available to US smokers. Average daily percentage changes (ADPCs) were used to measure trends for the entire 2020 and 2019 study periods, whereas daily percentage changes (DPCs) were used to measure trends for each time segment of change within each 4-month period. Data analysis was conducted in May and June 2020. Results The number of new daily visitors on the SmokeFree website (between days 39 and 44: DPC=18.79%; 95% CI 5.16% to 34.19%) and subscribers to the adult-focused interventions QuitGuide (between days 11 and 62: DPC=1.11%; 95% CI 0.80% to 1.43%) and SmokeFreeTXT (between days 11 and 89: DPC=0.23%; 95% CI 0.004% to 0.47%) increased, but this was followed by declines in traffic. No comparable peaks were observed in 2019. The number of new daily subscribers to quitSTART (ie, the teen-focused intervention) trended downward in 2020 (ADPC=−1.02%; 95% CI −1.88% to −0.15%), whereas the overall trend in the number of subscribers in 2019 was insignificant (P=.07). The number of SmokeFree social media account followers steadily increased by <0.1% over the 4-month study periods in 2019 and 2020. Conclusions Peaks in traffic on the SmokeFree website and adult-focused intervention platforms in 2020 could be attributed to an increased interest in smoking cessation among smokers during the COVID-19 pandemic. Coordinated campaigns, especially those for adolescents, should emphasize the importance of smoking cessation as a preventive measure against SARS-CoV-2 infection and raise awareness of digital smoking cessation platforms to capitalize on smokers’ heightened interest during the pandemic.
Short‐term exposure to synthetic flaxseed lignan LGM2605 alters gut microbiota in mice

LGM2605 is a synthetic version of the naturally occurring flaxseed lignan secoisolariciresinol diglucoside (SDG), with known anti‐inflammatory and antioxidant properties; however, its effects on gut microbial composition have not previously been evaluated. In the present study, we sought to determine how the 10‐day oral administration of LGM2605 alters the gut microbiota of mice. Eight‐week‐old female C57BL/6 mice were treated with either LGM2605 or saline, administered daily via oral gavage over a 10‐day treatment period. Upon termination of treatment, mouse cecums (n = 31) were collected, and cecal DNA was isolated. 16S rRNA genes were sequenced and analyzed in Mothur to identify changes in gut microbial composition induced by LGM2605 treatment (v. saline control). We then assessed community composition, performed indicator taxa analysis, and measured alpha and beta diversity. Overall, LGM2605 significantly altered the gut microbiota of mice; we reported alterations in 3 bacterial phyla and 22 genera as a result of treatment. The study here identifies for the first time significant alterations in the gut microbiota of mice following oral administration of LGM2605, in general shifting toward a more anti‐inflammatory composition. These findings lay the foundation for future investigations utilizing LGM2605 to control gut dysbiosis and, by extension, systemic inflammation.
Gastric amyloidosis in a patient with dysphagia

Dysphagia is a symptom with a broad differential diagnosis. Usually, the etiology of dysphagia is benign, but it is essential to rule out serious causes. It is also critical to think outside the box when the etiology is not obvious. Herein, we describe a case of multiple myeloma that initially presented with dysphagia. An 81-year-old male patient presented with dysphagia to solid food associated with anorexia and weight loss of 22 kg over the last 6 months. The patient looked chronically ill and cachectic. Upper endoscopy showed patchy erythema in the gastric antrum. Gastric biopsy was consistent with gastric amyloidosis. Although serum and urine protein electrophoresis did not show a monoclonal (M) band, immunofixation did show elevated free kappa light chains and elevated free Kappa/Lambda ratio. Bone marrow biopsy was consistent with multiple myeloma. Although gastrointestinal involvement is common in amyloidosis, it is unusual for amyloidosis to initially present in the gastrointestinal tract. Identification and treatment of the underlying condition, e.g., multiple myeloma, can lead to regression of gastrointestinal amyloidosis.
The use of alkaline phosphatase and possible alternative testing to verify pasteurisation of raw milk, colostrum, dairy and colostrum‐based products

Abstract Pasteurisation of raw milk, colostrum, dairy or colostrum‐based products must be achieved using at least 72°C for 15 s, at least 63°C for 30 min or any equivalent combination, such that the alkaline phosphatase (ALP) test immediately after such treatment gives a negative result. For cows’ milk, a negative result is when the measured activity is ≤ 350 milliunits of enzyme activity per litre (mU/L) using the ISO standard 11816‐1. The use and limitations of an ALP test and possible alternative methods for verifying pasteurisation of those products from other animal species (in particular sheep and goats) were evaluated. The current limitations of ALP testing of bovine products also apply. ALP activity in raw ovine milk appears to be about three times higher and in caprine milk about five times lower than in bovine milk and is highly variable between breeds. It is influenced by season, lactation stage and fat content. Assuming a similar pathogen inactivation rate to cows’ milk and based on the available data, there is 95–99% probability (extremely likely) that pasteurised goat milk and pasteurised sheep milk would have an ALP activity below a limit of 300 and 500 mU/L, respectively. The main alternative methods currently used are temperature monitoring using data loggers (which cannot detect other process failures such as cracked or leaking plates) and the enumeration of Enterobacteriaceae (which is not suitable for pasteurisation verification but is relevant for hygiene monitoring). The inactivation of certain enzymes other than ALP may be more suitable for the verification of pasteurisation but requires further study. Secondary products of heat treatment are not suitable as pasteurisation markers due to the high temperatures needed for their production. More research is needed to facilitate a definitive conclusion on the applicability of changes in native whey proteins as pasteurisation markers.
Secreted frizzled-related protein 4 promotes brown adipocyte differentiation

Secreted frizzled-related protein 4 (SFRP4) is a member of the SFRP family that contains a cysteine-rich domain homologous to the putative Wnt-binding site of frizzled proteins. In the present report, the effects of SFRP4 on murine brown adipocyte differentiation were evaluated, which exhibited an intrinsic capacity to differentiate with high efficiency. Brown preadipocytes were isolated from the scapular region of brown adipose tissue, which showed that the overexpression of recombinant active SFRP4 protein at three concentrations (1, 10 and 100 ng/ml) significantly increased the expression of adipocyte differentiation-associated genes (C/EBPα, C/EBPβ, UCP-1, PRDM16, PGC1α and GLUT4) in a dose-dependent manner compared with the control group. Secondly, adiponectin protein expression was significantly inhibited in a dose-independent manner, while leptin was increased in brown adipocytes by incubation with the high concentration (100 ng/ml) of SFRP4. Thirdly, the role of interleukin-1β (IL-1β) was investigated in brown adipocytes and discovered that IL-1β cannot induce SFRP4 mRNA expression in brown adipocytes, similar to human islet cells. These data suggested that SFRP4-treated brown adipocytes represent a valuable in vitro model for the study of adipogenesis and indicated that SFRP4 served various functions during brown adipocyte differentiation.
Effect of COVID‐19 on health system integration in the Netherlands: a mixed‐methods study

Overcrowding in acute care services gives rise to major problems, such as reduced accessibility and delay in treatment. In order to be able to continue providing high‐quality health care, it is important that organizations are well integrated at all organizational levels. The objective of this study was to to gain an understanding in which extent cooperation within an urban acute care network in the Netherlands (The Hague) improved because of the COVID‐19 crisis.
The molecular mechanism of CFTR‐ and secretin‐dependent renal bicarbonate excretion

This review summarizes the newly discovered molecular mechanism of secretin‐stimulated urine HCO3– excretion and the role of cystic fibrosis transmembrane conductance regulator (CFTR) in renal HCO3– excretion. The secretin receptor is functionally expressed in the basolateral membrane of the HCO3–‐secreting β‐intercalated cells of the collecting duct. Here it activates a fast and efficient secretion of HCO3– into the urine serving to normalize metabolic alkalosis. The ability to acutely increase renal base excretion is entirely dependent on functional pendrin (SLC26A4) and CFTR, and both proteins localize to the apical membrane of the β‐intercalated cells. In cystic fibrosis mice and patients, this function is absent or markedly reduced. We discuss that the alkaline tide, namely the transient urine alkalinity after a meal, has now received a clear physiological explanation.
Predicting anti-PD-1 responders in malignant melanoma from the frequency of S100A9+ monocytes in the blood

Background While programmed cell death receptor 1 (PD-1) blockade treatment has revolutionized treatment of patients with melanoma, clinical outcomes are highly variable, and only a fraction of patients show durable responses. Therefore, there is a clear need for predictive biomarkers to select patients who will benefit from the treatment. Method To identify potential predictive markers for response to PD-1 checkpoint blockade immunotherapy, we conducted single-cell RNA sequencing analyses of peripheral blood mononuclear cells (PBMC) (n=8), as well as an in-depth immune monitoring study (n=20) by flow cytometry in patients with advanced melanoma undergoing treatment with nivolumab at Karolinska University Hospital. Blood samples were collected before the start of treatment and at the time of the second dose. Results Unbiased single-cell RNA sequencing of PBMC in patients with melanoma uncovered that a higher frequency of monocytes and a lower ratio of CD4+ T cells to monocyte were inversely associated with overall survival. Similarly, S100A9 expression in the monocytic subset was correlated inversely with overall survival. These results were confirmed by a flow cytometry-based analysis in an independent patient cohort. Conclusion Our results suggest that monocytic cell populations can critically determine the outcome of PD-1 blockade, particularly the subset expressing S100A9, which should be further explored as a possible predictive biomarker. Detailed knowledge of the biological role of S100A9+ monocytes is of high translational relevance.
Reference data for hop tests used in pediatric ACL injury rehabilitation: A cross‐sectional study of healthy children

In rehabilitation, four single‐leg hop tests are frequently used for evaluation of ACL‐injured children. However, reference values on single‐leg hop performance and the corresponding limb symmetry indexes (LSIs) of healthy children younger than 15 years of age are lacking. Thus, the purpose was to describe hop performance and LSIs in healthy Danish children, and to quantify the proportion of participants passing LSI values of ≥85% as well as ≥90%. Healthy children aged 9–15 years were invited to participate in the study. Hop performance (single hop, 6‐m timed hop, triple hop, and cross‐over hop) was assessed for each leg for each hop test and expressed as absolute, normalized (to body height), and LSI values. Descriptive statistics were applied to calculate mean ±SD for all outcomes within age and gender groups. Further, the 95% reference interval was calculated for each age and gender group. A total of 531 healthy children (52% girls) were included in the study, representing seven age groups (9‐15 years). The LSI group means across all participants for the four hop tests ranged between 84 and 95%. Between 70 and 83% of the children had an LSI of ≥85%, while 50 to 65% of the children had an LSI of ≥90%. The present reference material can be used in clinical practice when evaluating hop performance in pediatric ACL patients.
A novel family of nonribosomal peptides modulate collective behavior in Pseudovibrio bacteria isolated from marine sponges

Collective behavior is a common feature of life. Although swarming motility and biofilms are opposed collective behaviors, both contribute to bacterial survival and host colonization. We have identified a link between motility/biofilms and a nonribosomal peptide synthetase-polyketide synthase gene cluster family (ppp) conserved in Pseudovibrio and Pseudomonas Proteobacteria known to interact with diverse eukaryotes. After developing reverse genetics for Pseudovibrio, we discovered two pseudovibriamide families, heptapeptides with a reversal in chain polarity via an ureido linkage 1-6 and related nonadepsipeptides 7-12. Imaging mass spectrometry showed that 1 was excreted whereas 7 was colony-associated. Deletion of pppA abolished production of 1-12 leading to reduced motility and increased biofilm production. pppD mutants that produced only 1-6 showed motility comparable to the wild-type and reduced biofilm formation, indicating that the excreted heptapeptides play a role in promoting motility. In contrast to lipopeptides widely known to affect swarming and biofilms, pseudovibriamides are not surfactants. Our results expand current knowledge on metabolites mediating bacterial collective behavior. Moreover, the establishment of reverse genetics will enable future exploration of the ecological and biotechnological potential of Pseudovibrio bacteria which have been proposed to contribute to marine sponge health. Significance Bacteria contribute to health and disease of plants and animals. Specialized metabolites produced by bacteria are important in mediating their behavior and the colonization of their hosts. We have identified a conserved gene cluster family in Pseudovibrio and Pseudomonas bacteria known to colonize marine animals and terrestrial plants, respectively. Using Pseudovibrio as a model, we show the encoded metabolites, which we termed pseudovibriamides, promote motility and decrease biofilms. In contrast to lipopeptides widely known to affect motility/biofilms, pseudovibriamides are not surfactants, but instead are linear peptides with a reversal in chain polarity. The discovery of pseudovibriamides expands current knowledge of bacteria collective behavior. The establishment of reverse genetics will enable exploration of the ecological and biotechnological potential of Pseudovibrio bacteria. Classification Biological Sciences, Microbiology
Chronic Low Back Pain Occurring in Association With Hypermobility Spectrum Disorder and Ehlers-Danlos Syndrome

ABSTRACT Background: This review paper outlines recent advances in diagnostic criteria for hypermobility spectrum disorder (HSD) and its association with Ehlers-Danlos syndrome (EDS), as well as current literature on the association between joint hypermobility syndrome and lumbar back pain. We outline the optimal multidisciplinary management of lumbar back pain in the context of joint hypermobility syndrome, as well as the indications and possible side effects of surgical management of patients with these conditions. Several studies have suggested a link between chronic low back pain and hypermobility. HSD has been described as an excessive range of motion in a joint, when accounting for patient demographics. The nomenclature surrounding symptomatic joint hypermobility has varied historically, and various groups, including most notably the international EDS consortium, have introduced new classification schemes to acknowledge the systemic effects of joint hypermobility, which were previously poorly understood. Methods: Narrative literature review. Results: Not applicable. Conclusions: Lower back pain experienced in patients on the HSD-EDS spectrum is multifactorial in origin and should not be considered solely in anatomical terms. Caution has been advised in the surgical management of patients on the HSD-hEDS spectrum, particularly where the subtype is unclear. The vascular type of EDS has a particular propensity for severe bleeding complications. Rates of perioperative complications after lumbar spinal surgery in the hypermobile EDS population have been reported to be up to 50%. When hypermobility and chronic lumbar back pain coexist, we advocate management in a multidisciplinary setting involving physiotherapists, pain physicians, surgeons, and psychologists.
Protein–DNA/RNA Interactions: An Overview of Investigation Methods in the -Omics Era

The fields of application of functional proteomics are not limited to the study of protein–protein interactions; they also extend to those involving protein complexes that bind DNA or RNA. These interactions affect fundamental processes such as replication, transcription, and repair in the case of DNA, as well as transport, translation, splicing, and silencing in the case of RNA. Analytical or preparative experimental approaches, both in vivo and in vitro, have been developed to isolate and identify DNA/RNA binding proteins by exploiting the advantage of the affinity shown by these proteins toward a specific oligonucleotide sequence. The present review proposes an overview of the approaches most commonly employed in proteomics applications for the identification of nucleic acid-binding proteins, such as affinity purification (AP) protocols, EMSA, chromatin purification methods, and CRISPR-based chromatin affinity purification, which are generally associated with mass spectrometry methodologies for the unbiased protein identification.
Fatigue Detection of Pilots’ Brain Through Brains Cognitive Map and Multilayer Latent Incremental Learning Model

This work proposes a nonparametric prior induced deep sum-logarithmic-multinomial mixture (DSLMM) model to detect pilots’ cognitive states through the developed brain power map. DSLMM uses multinormal distribution to infer the latent variable of each neuron in the first layer of the network. These latent variables obeyed a sum-logarithmic distribution that is backpropagated to its observation vector and the number of neurons in the next layer. Multinormal distribution is used to segment the extended observation vector to form a matrix associated with the width of the next layer. This work also proposes an adaptive topic-layer stochastic gradient Riemann (ATL-SGR) Markov chain Monte Carlo (MCMC) inference method to learn its global parameters without heuristic assumptions. The experimental results indicate that DSLMM can extract more probability distribution contained in the brain power map layer by layer, and achieve higher pilot cognition detection accuracy.