Miracle-dz/UniFAR-FTUs huggingface dataset:
Human Papillomavirus in Patients With Hypopharyngeal Squamous Cell Carcinoma

Objective Assess the testing rates and prognostic significance of human papilloma virus (HPV) status in hypopharynx malignancies. Study Design Historical cohort study. Setting National Cancer Database. Methods Review of the National Cancer Database was conducted between 2010 and 2017 for squamous cell carcinomas (SCCs) of the hypopharynx. We investigated how often the tumors were tested for HPV and whether it was associated with survival outcomes. Results A total of 13,269 patients with hypopharynx malignancies were identified. Most cases were not tested for HPV status (n = 8702, 65.6%). Of those tested, 872 (19.1%) were positive for HPV and 3695 (80.9%) were negative. The proportion of nonoropharyngeal SCCs tested for HPV increased nearly every year during the study, with roughly one-third of cases (31.9%) being tested in 2017. In the facilities classified as high-testing centers of nonoropharyngeal SCCs of the head and neck, 18.7% of hypopharyngeal tumors were HPV positive. HPV-negative status was associated with worse survival on multivariable analysis. In propensity score–matched analysis controlling for all factors significant in multivariable regression, 2-year survival remained higher in the HPV-positive cohort (77.7% vs 63.1%, P < .001). Conclusions HPV-positive tumors constitute a sizable minority of hypopharynx tumors and are associated with improved survival. Expansion of HPV testing to hypopharynx malignancies may be warranted.
Microbiota-derived short chain fatty acids modulate microglia and promote Aβ plaque deposition

Previous studies have identified a crucial role of the gut microbiome in modifying Alzheimer’s disease (AD) progression. However, the mechanisms of microbiome–brain interaction in AD were so far unknown. Here, we identify microbiota-derived short chain fatty acids (SCFA) as microbial metabolites which promote Aβ deposition. Germ-free (GF) AD mice exhibit a substantially reduced Aβ plaque load and markedly reduced SCFA plasma concentrations; conversely, SCFA supplementation to GF AD mice increased the Aβ plaque load to levels of conventionally colonized (specific pathogen-free [SPF]) animals and SCFA supplementation to SPF mice even further exacerbated plaque load. This was accompanied by the pronounced alterations in microglial transcriptomic profile, including upregulation of ApoE. Despite increased microglial recruitment to Aβ plaques upon SCFA supplementation, microglia contained less intracellular Aβ. Taken together, our results demonstrate that microbiota-derived SCFA are critical mediators along the gut-brain axis which promote Aβ deposition likely via modulation of the microglial phenotype.
ATP2B1 gene polymorphisms rs2681472 and rs17249754 are associated with susceptibility to hypertension and blood pressure levels

Abstract Objective: The present study aimed to conduct a systematic review and meta-analysis to evaluate the relationships between ATP2B1 gene polymorphisms with blood pressure (BP) level and susceptibility to hypertension. Methods: PubMed, Web of Science, Embase and China National Knowledge Infrastructure (CNKI) Databases were systematically searched by 2 independent researchers to screen studies on ATP2B1 gene polymorphisms and BP related phenotypes. The records retrieval period was limited from the formation of the database to March 4, 2021. Pooled odds rations (ORs) or β and their 95% confidence intervals (95%CI) were calculated to assess the association between ATP2B1 gene polymorphisms and the risk of hypertension or BP levels. Publication bias and sensitivity analysis were conducted to find potential bias. All the statistical analysis were conducted with Stata version 11.0 software. Results: A total of 15 articles were ultimately included in the present study, including 15 polymorphisms of ATP2B1 gene. Nine articles (N = 65,362) reported the polymorphism rs17249754, and 7 articles(N = 91,997) reported rs2681472 (both loci were reported in 1 article). Meta-analysis showed that rs17249754 (G/A) and rs2681472 (A/G) were associated with the susceptibility to hypertension (rs17249754: OR = 1.19, 95%CI: 1.10–1.28; rs2681472: OR = 1.15, 95%CI: 1.12–1.17), and were positively associated with systolic BP (SBP) and diastolic blood pressure (DBP) (rs17249754: SBP, β=1.01, 95%CI: 0.86–1.16, DBP, β=0.48, 95%CI: 0.30–0.66; rs2681472: SBP, β=0.92, 95%CI: 0.77–1.07, DBP, β=0.50, 95%CI: 0.42–0.58) in the additive genetic model. Subgroup analysis stratified by race, population, sample size, and BP measurement method revealed that the association between A allele in rs2681472 polymorphism and risk of hypertension was slightly stronger in European (EUR) populations (OR = 1.16, 95%CI: 1.13–1.20) than in East Asians (OR = 1.14, 95%CI: 1.10–1.17). While in East Asians, relation between rs17249754 with risk of hypertension (OR = 1.19, 95%CI: 1.10–1.28) is stronger than rs2681472 (OR = 1.14, 95%CI: 1.10–1.17). Conclusions: Our study demonstrated that ATP2B1 gene polymorphism rs2681472 and rs17249754 were associated with BP levels and the susceptibility to hypertension.
The Human Islet: Mini-organ with Mega-impact.

This review focuses on the human pancreatic islet - including its structure, cell composition, development, function, and dysfunction. After providing a historical timeline of key discoveries about human islets over the past century, we describe new research approaches and technologies that are being used to study human islets and how these are providing insight into human islet physiology and pathophysiology. We also describe changes or adaptations in human islets in response to physiologic challenges such as pregnancy, aging, and insulin resistance and discuss islet changes in human diabetes of many forms. We outline current and future interventions being developed to protect, restore, or replace human islets. The review also highlights unresolved questions about human islets and proposes areas where additional research on human islets is needed.
Comparison of Outcomes of Enoxaparin Bridge Therapy in HeartMate II versus HeartWare HVAD Recipients

Background: There is a lack of robust data evaluating outcomes of enoxaparin “bridge” therapy in left ventricular assist device (LVAD) patients. Methods: We performed a retrospective study of HeartMate II (HM II) and HeartWare HVAD recipients that received therapeutic enoxaparin as “bridge” therapy to describe bleeding and thrombotic events and compare outcomes between devices. The primary endpoint was the incidence of bleeding within 30 days of “bridge” episode. Major bleeding was defined by INTERMACS criteria. Results: We evaluated 257 “bridge” episodes in 54 patients, 35 with a HM II device and 19 with an HVAD device that underwent 176 and 81 bridging episodes, respectively. The median INR prior to “bridge” was lower in the HM II group compared to the HVAD group (1.5 vs 1.7, P < .01), however, there was no difference in the median duration of “bridge” therapy (7 vs 7 days, P = .42). There were a total of 30 (12%) bleeding episodes, with the majority in the HM II group vs HVAD (26 [15%] vs 4 [5%], P = .02). We observed 3 (1%) thromboembolic events in 2 (4%) patients with an HVAD device. On multivariate analysis, the presence of a HM II device was associated with a 4-fold increased risk of bleeding. Conclusion: We found the use of enoxaparin “bridge” therapy to be associated with a higher incidence of bleeding in patients with a HM II device compared with an HVAD device. Assessment of device- and patient-specific factors should be evaluated to minimize bleeding events.
Innate lymphoid cell recovery and occurrence of GvHD after hematopoietic stem cell transplantation

Lymphocytes are essential for microbial immunity, tumor surveillance, and tissue homeostasis. However, the in vivo development and function of helper‐like innate lymphoid cells (ILCs) in humans remain much less well understood than those of T, B, and NK cells. We monitored hematopoietic stem cell transplantation (HSCT) to determine the kinetics of ILC development in both children and adults. It was found that, unlike NK cells, helper‐like ILCs recovered slowly, mirroring the pattern observed for T cells, with normalization achieved at 1 year. The type of graft and the proportion of CD34+ cells in the graft did not significantly affect ILC reconstitution. As HSCT is often complicated by acute or chronic graft‐versus‐host disease (GVHD), the potential role of ILC subsets in maintaining tissue integrity in these conditions was also analyzed. It was found that GVHD was associated with lower levels of activated and gut‐homing NKp44+ ILCP, consistent with a non‐redundant role of this ILC subset in preventing this life‐threatening disorder in lymphopenic conditions.
Optogenetic control of neural differentiation in Opto‐mGluR6 engineered retinal pigment epithelial cell line and mesenchymal stem cells

In retinal degenerative disorders, when neural retinal cells are damaged, cell transplantation is one of the most promising therapeutic approaches. Optogenetic technology plays an essential role in the neural differentiation of stem cells via membrane depolarization. This study explored the efficacy of blue light stimulation in neuroretinal differentiation of Opto‐mGluR6‐engineered mouse retinal pigment epithelium (mRPE) and bone marrow mesenchymal stem cells (BMSCs). mRPE and BMSCs were selected for optogenetic study due to their capability to differentiate into retinal‐specific neurons. BMSCs were isolated and phenotypically characterized by the expression of mesenchymal stem cell‐specific markers, CD44 (99%) and CD105 (98.8%). mRPE culture identity was confirmed by expression of RPE‐specific marker, RPE65, and epithelial cell marker, ZO‐1. mRPE cells and BMSCs were transduced with AAV‐MCS‐IRES‐EGFP‐Opto‐mGluR6 viral vector and stimulated for 5 days with blue light (470 nm). RNA and protein expression of Opto‐mGluR6 were verified. Optogenetic stimulation‐induced elevated intracellular Ca2+ levels in mRPE‐ and BMS‐treated cells. Significant increase in cell growth rate and G1/S phase transition were detected in mRPE‐ and BMSCs‐treated cultures. Pou4f1, Dlx2, Eomes, Barlh2, Neurod2, Neurod6, Rorb, Rxrg, Nr2f2, Ascl1, Hes5, and Sox8 were overexpressed in treated BMSCs and Barlh2, Rorb, and Sox8 were overexpressed in treated mRPE cells. Expression of Rho, Thy1, OPN1MW, Recoverin, and CRABP, as retinal‐specific neuron markers, in mRPE and BMS cell cultures were demonstrated. Differentiation of ganglion, amacrine, photoreceptor cells, and bipolar and Muller precursors were determined in BMSCs‐treated culture and were compared with mRPE. mRPE cells represented more abundant terminal Muller glial differentiation compared with BMSCs. Our results also demonstrated that optical stimulation increased the intracellular Ca2+ level and proliferation and differentiation of Opto‐mGluR6‐engineered BMSCs. It seems that optogenetic stimulation of mRPE‐ and BMSCs‐engineered cells would be a potential therapeutic approach for retinal degenerative disorders.
Increased heterogeneity of brain perfusion predicts the development of cerebrovascular accidents

Abstract The heterogeneity of brain perfusion is related to the risk factors of thromboembolic events such as antiphospholipid syndrome. However, the effectiveness of brain perfusion heterogeneity as a marker to predict thromboembolic events has not been confirmed. Our objective was to evaluate the effectiveness of brain perfusion heterogeneity as a marker to predict the development of cerebrovascular accidents. In this retrospective cohort study, patients who underwent Tc-99m ECD brain SPECT from January 1, 2006 through December 31, 2008 were included. Each study was reoriented with the Talairach space provided by the NeuroGam Software package. Heterogeneity of brain perfusion was measured as the coefficient of variation. The study outcome was the risk of cerebral vascular accidents in patients with increased heterogeneity of brain perfusion between January 1, 2006 and December 31, 2015. A multiple Cox proportional hazards model was applied to evaluate the risk of cerebrovascular accidents. A total of 70 patients were included in this study. The median age was 39 years (range, 28 – 59 years). There were 55 (78.6%) women. For increased heterogeneity of brain perfusion, the hazard ratio of cerebrovascular accidents was 2.68 (95% CI, 1.41 – 5.09; P = .003) after adjusting for age, sex, hypertension, diabetes mellitus, and dyslipidemia. Our study suggests that increased heterogeneity of brain perfusion is associated with an increased risk of cerebrovascular accidents.
Transactions between self-esteem and perceived conflict in romantic relationships: A 5-year longitudinal study

Self-esteem has been shown to be both predictive of and predicted by characteristics of romantic relationships. While there is an increasing number of studies yielding support for reciprocal influences between self-esteem and perceived conflict in romantic relationships, longitudinal transactions between these constructs from both partners’ perspectives have not been studied systematically to date. Our aim was to close this gap. To that end, we examined the transactional and longitudinal interplay between self-esteem and perceived relationship conflict in continuing romantic couples from a dyadic perspective. Our sample consisted of N = 1,093 young adult female–male relationships from the German Family Panel. Individuals’ self-esteem, perceived conflict frequency, and their perceptions of their partners’ dysfunctional conflict styles (i.e., unconstructive behavior, withdrawal) were examined annually throughout a time span of five years. Based on dyadic bivariate latent change models, we tested our assumption that self-esteem and aspects of perceived relationship conflict are negatively interrelated within individuals and between partners both within and across time. We found one actor effect of self-esteem on changes in unconstructive behavior above and beyond initial unconstructive behavior levels, supporting self-broadcasting perspectives. Moreover, we found strong support for sociometer perspectives. Actor effects highlighted the importance of perceived conflict frequency for subsequent self-esteem changes. In addition, perceived conflict styles affected both partners’ self-esteem. The results imply that perceiving conflict is a between-person process, and might be more important for the development of self-esteem than vice versa.
Transcatheter Aortic Valve Replacement Versus Surgical Aortic Valve Replacement: How Would You Manage This Patient With Severe Aortic Stenosis?

Aortic stenosis (AS) is common, especially among the elderly. Left untreated, severe symptomatic AS is typically fatal. Surgical aortic valve replacement (SAVR) was the standard of care until transcatheter aortic valve replacement (TAVR) was shown to have lower mortality rates in patients at the highest surgical risk and was recommended for this group in the 2014 American Heart Association/American College of Cardiology (AHA/ACC) guidelines. In the 2017 AHA/ACC focused update, evidence of benefit and noninferiority extended the use of TAVR to intermediate-risk patients. More recent studies suggest potential benefit to low-risk patients, although no published guidelines yet recommend the use of TAVR for this population. An advantage of SAVR is a 30-year experience with valve durability, but SAVR may have higher rates of perioperative death and a slower return of quality of life. Although TAVR has less than 10-year experience with valve durability, it has lower or noninferior primary end points, such as mortality and stroke, and fewer periprocedural complications among anatomically permissive patients. Here, a cardiologist and a cardiothoracic surgeon debate the risks and benefits of TAVR versus SAVR for a patient with severe symptomatic AS who is at low risk for surgical death.
Extremely low surface recombination in 1 Ω cm n‐type monocrystalline silicon

A key requirement in the recent development of highly efficient silicon solar cells is the outstanding passivation of their surfaces. In this work, plasma enhanced chemical vapour deposition of a triple layer dielectric consisting of amorphous silicon, silicon oxide and silicon nitride, charged extrinsically using corona, has been used to demonstrate extremely low surface recombination. Assuming Richter's parametrisation for bulk lifetime, an effective surface recombination velocity Seff = 0.1 cm/s at Δn = 1015 cm–3 has been obtained for planar, float zone, n ‐type, 1 Ω cm silicon. This equates to a saturation current density J0s = 0.3 fA/cm2, and a 1‐sun implied open‐circuit voltage of 738 mV. These surface recombination parameters are among the lowest reported for 1 Ω cm c‐Si. A combination of impedance spectroscopy and corona‐lifetime measurements shows that the outstanding chemical passivation is due to the small hole capture cross section for states at the interface between the Si and a‐Si layer which are hydrogenated during nitride deposition. (© 2016 The Authors. Phys. Status Solidi RRL published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
GPER mediates estrogen cardioprotection against epinephrine-induced stress.

Currently, there are no conventional treatments for stress-induced cardiomyopathy (SCM, also known as Takotsubo syndrome), and the existing therapies are not effective. The recently discovered G protein- coupled estrogen receptor (GPER) executes the rapid effects of estrogen (E2). In this study, we investigated the effects and mechanism of GPER on epinephrine (Epi)-induced cardiac stress. SCM was developed with a high dose of Epi in adult rats and human-induced pluripotent stem cells-derived cardiomyocytes(hiPSC-CMs). (1) GPER activation with agonist G1/ E2 prevented an increase in left ventricular internal diameter at end-systole, the decrease both in ejection fraction and cardiomyocyte shortening amplitude elicited by Epi. (2) G1/ E2 mitigated heart injury induced by Epi, as revealed by reduced plasma brain natriuretic peptide and lactate dehydrogenase release into culture supernatant. (3) G1/E2 prevented the raised phosphorylation and internalization of β2-adrenergic receptors（β2AR）. (4) Blocking Gαi abolished the cardiomyocyte contractile inhibition by Epi. G1/E2 downregulated Gαi activity of cardiomyocytes and further upregulated cyclic adenosine monophosphate concentration in culture supernatant treated with Epi. (5) G1/E2 rescued decreased Ca2+ amplitude and Ca2+ channel current (ICa-L) in rat cardiomyocytes. Notably, the above effects of E2 were blocked by the GPER antagonist, G15. In hiPSC-CM (which expressed GPER, β1AR and β2ARs), knockdown of GPER by siRNA abolished E2 effects on increasing ICa-L and action potential duration in the stress state. In conclusion, GPER played a protective role against SCM. Mechanistically, this effect was mediated by balancing the coupling of β2AR to the Gαs and Gαi signalling pathways.
Porous discoidal polymeric particles for effective drug delivery minimizing phagocytosis

Abstract Curcumin has great potential in cancer treatment and prevention. However, free curcumin for anticancer effect is limited due to its low water solubility and instability. Delivery of free curcumin using biodegradable and biocompatible polymers, such as poly (lactic-co-glycolic acid) (PLGA), can improve these undesirable problems. In this study, a top-down fabrication method using PLGA was employed to deliver free curcumin, engineering size, shape, and surface properties. As a result, porous discoidal polymeric particles (DPPs) were produced in ammonium bicarbonate with a hydrodynamic diameter of 5 µm and a negatively charged surface. The loading amount of free curcumin in the porous DPPs was higher than non-porous DPPs. In vitro drug release study showed that curcumin release from porous DPPs was 1.4-fold higher than non-porous ones. The confocal microscopy and flow cytometry results demonstrated that porous DPPs decrease phagocytosis by macrophages than non-porous ones. This study suggests that porous DPPs have significant advantages for effective drug delivery of curcumin, minimizing phagocytosis. Graphical Abstract
Fluorescent chitosan nanoparticles as a carrier system for trackable drug delivery

ABSTRACT Chitosan (CS) is a biopolymer that presents remarkable biomedical applications. Here we report on the fluorescence study of water-soluble CS nanoparticles obtained by hydrothermal treatment at different temperatures and exposure times using hydrochloric acid as solvent. Average particle size varied from 1.69 μm to 112 nm for tested conditions. The fluorescence quantum yield of these CS NPs was increased by up to 75 times. Methotrexate (MTX) was incorporated in to CS NPs and our outcomes pointed out that the incorporation efficiency of MTX in to CS-NPs was 72.90%, and 25.30% (w/w) of the incorporated MTX was released in 96 h. Graphical Abstract
Authentic food experiences bring us back to the past: an investigation of a local food night market

ABSTRACT This study aims to investigate the authenticity-nostalgia nexus in food tourism experiences. Analysis of a convenience sample of 399 tourists visiting Hong Kung Night Market, a local food night market in Macao, revealed that both perceived food and atmosphere authenticity can trigger nostalgic emotion, which in turn enhances attitudes toward local food and gastronomy destination image, thus alluring tourists to return. Furthermore, the influence of atmosphere authenticity on nostalgic emotions is stronger for more experienced tourists. The results suggest that authentic and nostalgic cues should be leveraged to attract and retain tourists by DMOs and night market organizers.
Capturing a soil carbon economy

Current carbon pricing and trading mechanisms, despite their efficacy in reducing GHG emissions from industry, will not be sufficient to achieve Net Zero targets. Current mechanisms that redress emissions are largely economic disincentives, in effect financial penalties for emitters. In order to attain Net Zero futures, financial incentives for activities that sequester carbon from the atmosphere are needed. Herein, we present the environmental and economic co-benefits of soil re-carbonization and justify support for soil carbon remuneration. With increasing momentum to develop green economies, and projected increases in carbon price, growth in the global carbon market is inevitable. The establishment of a soil-based carbon economy, within this emerging financial space, has the potential to deliver a paradigm shift that will accelerate climate change mitigation, and concurrently realize net gains for soil health and the delivery of soil ecosystem services. Pivotal to the emergence of a global soil carbon economy will be a consensus on certification instruments used for long-term soil carbon storage, and the development of robust institutional agreements and processes to facilitate soil carbon trading.