Miracle-dz/UniFAR-FTUs huggingface dataset:
Implementing Automated Office Blood Pressure Measurement.

436 Why is it we talk and write so much about blood pressure (BP) measurement? Why another debate about yet another BP measurement methodology? Of all the important risk factors for cardiovascular disease (CVD), it is only BP measurement that attracts so much discussion and debate. The methodological approaches for measuring other CVD risk factors such as glucose, glycated hemoglobin, low-density lipoprotein cholesterol, non–high-density lipoprotein cholesterol, body weight, height, body mass index, waist circumference, and smoking status are well-defined and widely agreed upon. What distinguishes BP from these more easily measured CVD risk factors? First, and perhaps the most difficult to address from a measurement perspective, is the moment-to-moment biologic variability in BP. While most other CVD risk factors are characterized by some level of biologic variability, BP is unique in its volatility. Physical activity (even mild), emotional stress, and many other factors can result in sudden changes to one’s BP. Like other risk factors, BP changes over time (with age), especially in industrialized societies. Second, all the convenient and clinically practical methods for measuring BP are indirect measurements. The reference standard for BP measurement is intraarterial measurement, a precise, but impractical method for most clinical settings. Indirect measurement methods, on the contrary, generally depend on the use of a pressurized cuff to impede blood flow in an artery, usually the brachial artery. Precise determination of BP is essential. Clinicians rely on precise BP levels to predict and manage CVD risk, to accurately diagnose hypertension, to determine appropriate initial therapy for BP management in those with hypertension or elevated BP, and to assess patients’ progress toward goal BP. In recent years, the use of performance measures to evaluate quality in patient care has driven a new focus on assessment of all common CVD risk factors. BP control is a frequently used performance measure for these evaluations, further necessitating accurate methods for measuring and monitoring BP. Currently, office BP measurements are the most frequently used measure of control, with the last recorded office BP often cited as the performance measure.
The ER luminal C-terminus of AtSec62 is critical for male fertility and plant growth in Arabidopsis thaliana.

Protein translocation into the endoplasmic reticulum occurs either co- or post-translationally via the Sec translocation system. The Arabidopsis Sec post-translocon is composed of the protein-conducting Sec61 complex, the chaperone docking protein AtTPR7, the J-domain containing proteins AtERdj2A/B and the yet uncharacterised AtSec62. Yeast Sec62p is suggested to mainly function in posttranslational translocation, whereas mammalian Sec62 also interacts with ribosomes. In Arabidopsis, loss of AtSec62 leads to impaired growth and drastically reduced male fertility indicating the importance of AtSec62 in protein translocation and subsequent secretion in male gametophyte development. Moreover, AtSec62 seems to be divergent in function as compared to yeast Sec62p, since we were not able to complement the thermosensitive yeast mutant sec62-ts. Interestingly, AtSec62 has an additional third transmembrane domain in contrast to its yeast and mammalian counterparts resulting in an altered topology with the C-terminus facing the ER lumen instead of the cytosol. In addition, the AtSec62 C-terminus has proven to be indispensable for AtSec62 function, since a construct lacking the C-terminal region was not able to rescue the mutant phenotype in Arabidopsis. We thus propose that Sec62 acquired a unique topology and function in protein translocation into the ER in plants. This article is protected by copyright. All rights reserved.
Endoscopic features of gastrointestinal stromal tumor in the small intestine

Background/Aims Gastrointestinal stromal tumor (GIST) is one of the most common types of submucosal tumors (SMTs). Because of GIST’s malignant potential, it is crucial to differentiate it from other SMTs. The present study aimed to identify characteristic endoscopic findings of GISTs in the small intestine. Methods We reviewed the clinicopathological and endoscopic findings of 38 patients with endoscopically or surgically resected SMTs in the small intestine. SMTs were classified into GIST and non-GIST groups, and clinicopathological and endoscopic findings were compared between the 2 groups. Results Fifteen patients had GIST and 23 patients had other types of SMTs in the small intestine. Comparison of the endoscopic findings between the 2 groups revealed that dilated vessels in the surrounding mucosa were significantly more in number in the GIST group than in the non-GIST group (P<0.05). However, there were no other differences in endoscopic findings between the 2 groups. Among patients with GISTs, the presence of dilated vessels in the surrounding mucosa was not associated with bleeding risk, tumor size, or metastasis rate at diagnosis. Conclusions Dilated vessels in the surrounding mucosa, identified during balloon-assisted endoscopy, may be a diagnostic indicator for GIST in the small intestine. However, its clinical significance should be further analyzed.
Management and prevention of drug resistant infections in burn patients

ABSTRACT Introduction: Despite modern advances, the primary cause of death after burns remains infection and sepsis. A key factor in determining outcomes is colonization with multi-drug resistant (MDR) organisms. Infections secondary to MDR organisms are challenging due to lack of adequate antibiotic treatment, subsequently prolonging hospital stay and increasing risk of adverse outcomes. Areas covered: This review highlights the most frequent organisms colonizing burn wounds as well as the most common MDR bacterial infections. Additionally, we discuss different treatment modalities and MDR infection prevention strategies as their appropriate management would minimize morbidity and mortality in this population. We conducted a search for articles on PubMed, Web of Science, Embase, Cochrane, Scopus and UpToDate with applied search strategies including a combination of: “burns, ‘thermal injury,’ ‘infections,’ ‘sepsis,’ ‘drug resistance,’ and ‘antimicrobials. ’ Expert opinion: Management and prevention of MDR infections in burns is an ongoing challenge. We highlight the importance of preventative over therapeutic strategies, which are easy to implement and cost-effective. Additionally, targeted, limited use of antimicrobials can be beneficial in burn patients. A promising future area of investigation within this field is post-trauma microbiome profiling. Currently, the best treatment strategy for MDR in burn patients is prevention.
miR-451a Inhibition Reduces Established Endometriosis Lesions in Mice

Endometriosis is an estrogen-dependent pro-inflammatory disease that affects 6% to 10% of reproductive-age women. Current treatments target sex steroids, and none are disease-specific. MicroRNA treatments have provided promising results for some chronic diseases and cancers. We have previously shown microRNA 451a is increased in endometriosis and that elevation of 451a contributes to the pathophysiology of the disease. Here, we propose inhibition of miR-451a for the treatment of endometriosis in a murine model. Endometriosis was treated using a microRNA 451a inhibitor or a scrambled control microRNA. Treatment with miR-451a inhibitor resulted in reduced endometriosis lesion size (30 vs 13 mm3). There was no difference in the number of visible lesions between the miR-451a treatment and controls. Treatment led to altered expression of several genes including YWHAZ, CAB39, MAPK1, β-catenin, and IL-6. Systemic treatment with a miR-451a inhibitor is a promising therapy for endometriosis that simultaneously affects multiple pathways driving the disease.
Augmentation of cellular NAD+ by NQO1 enzymatic action improves age‐related hearing impairment

Age‐related hearing loss (ARHL) is a major neurodegenerative disorder and the leading cause of communication deficit in the elderly population, which remains largely untreated. The development of ARHL is a multifactorial event that includes both intrinsic and extrinsic factors. Recent studies suggest that NAD+/NADH ratio may play a critical role in cellular senescence by regulating sirtuins, PARP‐1, and PGC‐1α. Nonetheless, the beneficial effect of direct modulation of cellular NAD+ levels on aging and age‐related diseases has not been studied, and the underlying mechanisms remain obscure. Herein, we investigated the effect of β‐lapachone (β‐lap), a known plant‐derived metabolite that modulates cellular NAD+ by conversion of NADH to NAD+ via the enzymatic action of NADH: quinone oxidoreductase 1 (NQO1) on ARHL in C57BL/6 mice. We elucidated that the reduction of cellular NAD+ during the aging process was an important contributor for ARHL; it facilitated oxidative stress and pro‐inflammatory responses in the cochlear tissue through regulating sirtuins that alter various signaling pathways, such as NF‐κB, p53, and IDH2. However, augmentation of NAD+ by β‐lap effectively prevented ARHL and accompanying deleterious effects through reducing inflammation and oxidative stress, sustaining mitochondrial function, and promoting mitochondrial biogenesis in rodents. These results suggest that direct regulation of cellular NAD+ levels by pharmacological agents may be a tangible therapeutic option for treating various age‐related diseases, including ARHL.
Concurrent nonalcoholic fatty liver disease and type 2 diabetes: diagnostic and therapeutic considerations

ABSTRACT Introduction: The relationship between nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) is complex and bidirectional. NAFLD increases the risk of incident diabetes and is very prevalent in T2DM patients and T2DM is an aggravating factor for NAFLD. Timely T2DM diagnosis and treatment in subjects with NAFLD and diagnosis, staging and treatment of NAFLD in those with T2DM are critical issues. Areas covered: PubMed/MEDLINE was searched for articles related to concomitant occurrence of NAFLD and T2DM between January 2013 and May 2019. Areas covered included epidemiological, diagnostic and therapeutic aspects. Expert opinion: there is a need for increased awareness on NAFLD adding liver disease as an end-organ complication of T2DM. Emphasis on use of simple non-invasive tools to triage patients with potentially severe liver disease should be made. Management of patients with NAFLD and T2DM relies on lifestyle optimization to achieve significant weight loss. Currently, there is no drug approved for treatment of NAFLD in patients with T2DM although Vitamin E and pioglitazone might be used in selected patients. Approved diabetic medications hold promise for NAFLD treatment and several liver-specific drugs are in evaluation clinical trials. A combination approach will likely represent the future of NAFLD therapeutics.
Sleep Disturbances Among Dialysis Patients

Sleep disturbances are extremely common among dialysis patients. Subjective sleep complaints are reported in up to 80% of patients and are characterized by difficulty in initiating and maintaining sleep, problems with restlessness, jerking legs, snoring, choking sensations and/or daytime sleepiness (Holley et al., 1992; Walker et al., 1995; Veiga et al., 1997). Epidemiological studies have found how sleep apnea syndrome (SAS), restless legs syndrome (RLS) and periodic limb movement disorder (PLMD) are much more prevalent than in the general population. These sleep problems appear to have significant negative effects on the quality of life as they are often cited as major sources of stress. Indeed, interviews of patients on hemodialysis and on peritoneal dialysis have found that sleep disturbances are one of the seven most distressing symptoms experienced (Eichel et al., 1986; Bass et al., 1999). Half of patients complaining of sleep disturbances feel that these problems affect their daily living and activity, and 21% consider that relief of this symptom would improve significantly their subjective quality of life (Parfrey et al., 1988; Iliescu et al., 2003). In the following sections two major sleep disturbances associated with Insomnia, Restless Legs Syndrome and Sleep Apnea Syndrome, will be reviewed in detail.
Apoplastic invasion patterns triggering plant immunity: plasma membrane sensing at the frontline

Summary Plants are able to effectively cope with invading pathogens by activating an immune response based on the detection of invasion patterns (IPs) originating from the pathogen or released by the plant after infection. At a first level, this perception takes place at the plasma membrane through cell surface immune receptors and although the involvement of proteinaceous pattern recognition receptors (PRRs) is well established, increasing data are also pointing out the role of membrane lipids in the sensing of IPs. In this review, we discuss the evolution of various conceptual models describing plant immunity and present an overview of well‐characterized IPs from different natures and origins. We summarize the current knowledge on how they are perceived by plants at the plasma membrane, highlighting the increasingly apparent diversity of sentinel‐related systems in plants.
The Involvement of Neuroinflammation in Dengue Viral Disease: Importance of Innate and Adaptive Immunity

Neuroinflammation (inflammation in brain) has been known to play an important role in the development of dengue virus disease. Recently, studies from both clinical and experimental models suggest the involvement of neuroinflammation in dengue viral disease. Studies in clinical setup demonstrated that, microglial cells are actively involved in the patients having dengue virus infection, showing involvement of innate immune response in neuroinflammation. It was further proved that, clinical isolates of dengue-2 virus were able to initiate the pathologic response when injected in the mice brain. Natural killer cells were also found to play a crucial role to activate adaptive immune response. Notably, CXCL10/IFN-inducible protein 10 and CXCR3 are involved in dengue virus-mediated pathogenesis and play an important role in the development of dengue virus-mediated paralysis. In a latest report, it was seen that intracranial injection of dengue virus increases the CD8+ T-cell infiltration in brain, showing an important mechanism of neuroinflammation during the dengue virus infection. A similar study has described that, when DENV-3 is injected into the mice, it enhances the infiltration of CD8+ and CD4+ T cells as well as neutrophils. Cells immune-reactive against NS3 antigen were found throughout the brain. In conclusion, we focus on the various molecular mechanisms which contribute to the basic understanding about the role of neuroinflammation in dengue fever. These mechanisms will help in better understanding dengue pathophysiology and thus help in the development of possible therapeutics.
Exploring Patterns in Preferences for Daily Care and Activities Among Nursing Home Residents.

Nursing homes have shifted from task-focused to person-centered care (PCC) environments. Understanding resident preferences for daily care and activities is fundamental to PCC. Examining resident similarities based on preferences may be useful for group or community-wide PCC planning. The aims of the current study were to group residents according to similarities in preferences and determine the factors that predict membership in these groups. A latent class analysis of resident preferences using data from the Minimum Data Set (N = 244,718) was conducted. Resident function, depression, cognitive impairment, and sociodemographics were used as predictors of class membership. The four-class model showed residents cluster around overall interest or disinterest in having choices about daily care and activities or specific interest in either care or activity preferences. Race and ethnicity, cognitive impairment, and depression predicted class membership. Findings suggest that residents can be grouped by preferences and knowledge of resident group membership could help direct efforts to systematically meet resident preferences. [Journal of Gerontological Nursing, 45(8), 7-13. ].
Novel approaches to anti-obesity drug discovery with gut hormones over the past 10 years

ABSTRACT Introduction: Obesity is a global pandemic and new pharmacotherapies which combine weight loss efficacy, long-term safety, and reversal of metabolic co-morbidities are sorely needed. Gut hormones play key roles in regulating satiety and metabolism, and are natural candidates for therapeutic development. Areas covered: The authors discuss recent drug developments for the treatment of obesity using gut hormones. The review was based on a search of PubMed using keywords ‘obesity’ AND (‘therapy’ OR ‘pharmacotherapy’ OR ‘gut hormones’ OR ‘analogues’), limited to the last 10 years. Expert opinion: Analogues of glucagon-like peptide (GLP-1) have been developed for obesity but so far do not provide enough weight loss. Bariatric surgery increases the post-prandial secretion of multiple gut hormones, leading to beneficial effects on weight loss and metabolism. This recognition has led to poly-agonist strategies: GLP-1/glucagon or GLP-1/glucose-dependent insulinotropic peptide (GIP) dual agonism, or even GLP-1/glucagon/GIP triple agonism. New delivery approaches include peptide-conjugate therapies that target key metabolic tissues. Practicable methods for oral delivery of peptide gut hormones are also close to market, expanding the potential market for these treatments. Anti-obesity therapy is therefore poised for an exciting phase, and it will be interesting to see which of these will eventually prevail.
Cognitive dissonance-based eating disorder prevention: pilot study of a cultural adaptation for the Orthodox Jewish community

ABSTRACT The Body Project (BP) is a cognitive dissonance-based eating disorders (ED) prevention program that targets thin-ideal internalization and reduces ED risk factors and onset for higher-risk adolescent/young adult females. Although the more insular Orthodox Jewish communities reduce exposure to mainstream secular media, they are not immune to thin-ideal internalization and EDs. The present uncontrolled study evaluated the preliminary effects of a cultural adaptation of the BP for Orthodox Jewish girls. The modified manual improved fit with ultra-Orthodox Jewish norms, practices, and values. Eighty-nine 11th-graders in a private, all-female religious high school participated. ED risk factors and symptoms were assessed at baseline, end of 4-week intervention, and 6-month follow-up. Multi-level modeling showed that body dissatisfaction and negative affect significantly decreased across time. Findings demonstrate potential for the BP to be adapted for and implemented in cultural and religious communities wherein interactions with societal influences on thin-ideal internalization differ from dominant culture.
A Wireless Electro-Optic Headstage With a 0.13-${\mu}$m CMOS Custom Integrated DWT Neural Signal Decoder for Closed-Loop Optogenetics

We present a wireless electro-optic headstage that uses a 0.13-<inline-formula><tex-math notation="LaTeX">${\mu}$</tex-math></inline-formula>m CMOS custom integrated circuit (IC) implementing a digital neural decoder (ND-IC) for enabling real-time closed-loop (CL) optogenetics. The ND-IC processes the neural activity data using three digital cores: 1) the <italic>detector core</italic> detects and extracts the action potential (AP) of individual neurons by using an adaptive threshold; 2) the data <italic>compression core</italic> compresses the detected AP by using an efficient Symmlet-2 discrete wavelet transform (DWT) processor for decreasing the amount of data to be transmitted by the low-power wireless link; and 3) the <italic>classification core</italic> sorts the compressed AP into separated clusters on the fly according to their wave shapes. The ND-IC encompasses several innovations: 1) the compression core decreases the complexity from O(n<inline-formula><tex-math notation="LaTeX">$^{2}$</tex-math></inline-formula>) to O(n<inline-formula><tex-math notation="LaTeX">$\cdot$</tex-math></inline-formula> log(n)) compared to the previous solutions, while using two times less memory, thanks to the use of a new coefficient sorting tree; and 2) the AP classification core reuses both the compressed DWT coefficients to perform implicit dimensionality reduction, which allows for performing intensive signal processing on-chip, while increasing power and hardware efficiency. This core also reuses the signal standard deviation already computed by the AP detector core as threshold for performing automatic AP sorting. The headstage also introduces innovations by enabling a new wireless CL scheme between the neural data acquisition module and the optical stimulator. Our CL scheme uses the AP sorting and timing information produced by the ND-IC for detecting complex firing patterns within the brain. The headstage is also smaller (1.13 cm<inline-formula><tex-math notation="LaTeX">$^{3}$</tex-math></inline-formula>), lighter (3.0 g with a 40 mAh battery) and less invasive than the previous solutions, while providing a measured autonomy of 2h40, with the ND-IC. The whole system and the ND-IC are first validated <italic>in vivo</italic> in the LD thalamus of a Long-Evans rat, and then in freely-moving CL experiments involving a mouse virally expressing ChR2-mCherry in inhibitory neurons of the prelimbic cortex, and the results show that our system works well within an <italic>in vivo</italic> experimental setting with a freely moving mouse.
Provocative questions in osteosarcoma basic and translational biology: A report from the Children's Oncology Group

Patients who are diagnosed with osteosarcoma (OS) today receive the same therapy that patients have received over the last 4 decades. Extensive efforts to identify more effective or less toxic regimens have proved disappointing. As we enter a postgenomic era in which we now recognize OS not as a cancer of mutations but as one defined by p53 loss, chromosomal complexity, copy number alteration, and profound heterogeneity, emerging threads of discovery leave many hopeful that an improving understanding of biology will drive discoveries that improve clinical care. Under the organization of the Bone Tumor Biology Committee of the Children's Oncology Group, a team of clinicians and scientists sought to define the state of the science and to identify questions that, if answered, have the greatest potential to drive fundamental clinical advances. Having discussed these questions in a series of meetings, each led by invited experts, we distilled these conversations into a series of seven Provocative Questions. These include questions about the molecular events that trigger oncogenesis, the genomic and epigenomic drivers of disease, the biology of lung metastasis, research models that best predict clinical outcomes, and processes for translating findings into clinical trials. Here, we briefly present each Provocative Question, review the current scientific evidence, note the immediate opportunities, and speculate on the impact that answered questions might have on the field. We do so with an intent to provide a framework around which investigators can build programs and collaborations to tackle the hardest problems and to establish research priorities for those developing policies and providing funding.