Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of Hexokinase in Stomata of Citrus Fruit Reduces Fruit Transpiration and Affects Seed Development

The temporal formation and spatial distribution of stomata on the surface of citrus floral organs and, specifically, on the ovule from which the fruit develops, were analyzed using citrus plants that express green fluorescent protein (GFP) under the guard cell-specific KST1 promoter. Stomata are found on the style, sepal, and anther of the closed flower and on ovules from the stage of anthesis. It has previously been shown that hexokinase (HXK) mediates sugar-sensing in leaf guard cells and stimulates stomatal closure. The activity and response of citrus fruit stomata to sugar-sensing by HXK was examined using plants that express HXK under the KST1 promoter. Those plants are referred to as GCHXK plants. The transpiration of young green GCHXK citrus fruits was significantly reduced, indicating that their stomata respond to sugar similar to leaf stomata. Toward fruit maturation, fruit stomata are plugged and stop functioning, which explains why WT and GCHXK mature yellow fruits exhibited similar water loss. Seeds of the GCHXK plants were smaller and germinated more slowly than the WT seeds. We suggest that the stomata of young green citrus fruits, but not mature yellow fruits, respond to sugar levels via HXK and that fruit stomata are important for proper seed development.
Marketing and Pricing Strategies of Blockbuster Drugs in the South Korean Market: A 15-Year Retrospective Cohort Study for Choline Alfoscerate

Introduction Understanding marketing strategies and price competition among manufacturers is essential to manage health care expenditures, particularly those related to blockbuster drugs. Objectives To assess marketing and pricing strategies of blockbuster drugs in South Korea. Methods Baseline information on manufacturers who were granted marketing approval for choline alfoscerate in various forms was retrieved. Accumulation of manufacturers in the market was also identified, and manufacturers were categorized into first movers and latecomers based on their marketing time. Then, an event history analysis and a regression analysis were applied to estimate the duration of marketing and their price competition. Results Currently, 109, 83, and 26 manufacturers produce choline alfoscerate in capsule, tablet, or syrup form, respectively, indicating that many manufacturers have marketed generics and the majority of the generics are categorized as latecomers. The size of the manufacturer was a significant factor in marketing new medicines, while the variable was not related to the marketing of modified drugs. Furthermore, price competition in the market was rare and only a few major firms initiated price competition. Conclusion The Korean market appears to be an example of perfect competition when we focus on the number of manufacturers. However, the market is near-monopolistic when examining the price of generic drugs. While product competition between different forms of drugs is effective in lowering price, product competition within the same form of a drug does not exist in the market.
Competition Between Butyrate Fermenters and Chain-Elongating Bacteria Limits the Efficiency of Medium-Chain Carboxylate Production

Medium-chain carboxylates such as n-caproate and n-caprylate are valuable chemicals, which can be produced from renewable feedstock by anaerobic fermentation and lactate-based microbial chain elongation. Acidogenic microbiota involved in lactate-based chain elongation and their interplay with lactic acid bacteria have not been characterized in detail yet. Here, the metabolic and community dynamics were studied in a continuous bioreactor with xylan and lactate as sole carbon sources. Four succession stages were observed during 148 days of operation. After an adaptation period of 36 days, a relatively stable period of 28 days (stage I) was reached with n-butyrate, n-caproate and n-caprylate productivities of 7.2, 8.2 and 1.8 gCOD L–1 d–1, respectively. After a transition period, the process changed to another period (stage II), during which 46% more n-butyrate, 51% less n-caproate and 67% less n-caprylate were produced. Co-occurrence networks of species based on 16S rRNA amplicon sequences and correlations with process parameters were analyzed to infer ecological interactions and potential metabolic functions. Diverse functions including hydrolysis of xylan, primary fermentation of xylose to acids (e.g., to acetate by Syntrophococcus, to n-butyrate by Lachnospiraceae, and to lactate by Lactobacillus) and chain-elongation with lactate (by Ruminiclostridium 5 and Pseudoramibacter) were inferred from the metabolic network. In stage I, the sub-network characterized by strongest positive correlations was mainly related to the production of n-caproate and n-caprylate. Lactic acid bacteria of the genus Olsenella co-occurred with potentially chain-elongating bacteria of the genus Pseudoramibacter, and their abundance was positively correlated with n-caproate and n-caprylate concentrations. A new sub-network appeared in stage II, which was mainly related to n-butyrate production and revealed a network of different lactic acid bacteria (Bifidobacterium) and potential n-butyrate producers (Clostridium sensu stricto 12). The synergy effects between lactate-producing and lactate-consuming bacteria constitute a division of labor cooperation of mutual benefit. Besides cooperation, competition between different taxa determined the bacterial community assembly over the four succession stages in this resource-limited system. During long-term reactor operation under constant conditions, chain-elongating bacteria were outcompeted by butyrate-producing bacteria, leading to the increase of n-butyrate yield at the cost of medium-chain carboxylate yields in this closed model system.
Shenlian Extract Against Myocardial Injury Induced by Ischemia Through the Regulation of NF-κB/IκB Signaling Axis

Ischemic heart disease (IHD), caused predominantly by atherosclerosis, is a leading cause of global mortality. Our previous studies showed that Shenlian extract (SL) could prevent the formation of atherosclerosis and enhance the stability of atherosclerotic plaques. To further investigate the protective effects of SL on myocardial ischemic injury and its possible mechanisms, anesthetized dogs, ex vivo rat hearts, and H9c2 cardiomyocytes were used as models. The results showed that SL had a significant protective effect on the anesthetized dog ligating coronary artery model, reduced the degree of myocardial ischemia (Σ-ST), and reduced the scope of myocardial ischemia (N-ST). Meanwhile, SL alleviated ischemic reperfusion damage in ex vivo rat hearts with improved LVEDP and ± dp/dtmax values of the left ventricle. SL reduced the pathological changes of LDH, IL-1β, MDA, and NO contents, all of which are related to the expression of NF-κB. Further analysis by Bio-Plex array and signal pathway blocker revealed that the phosphorylation of IκB was a key factor for SL to inhibit myocardial ischemic injury, and the regulation of SL on IκB was primarily related to degradation of the IκB protein. These results provided dependable evidence that SL could protect against myocardial ischemic injury through the NF-κB signaling pathway.
Antimicrobial Role of RNASET2 Protein During Innate Immune Response in the Medicinal Leech Hirudo verbana

The innate immune response represents a first-line defense against pathogen infection that has been widely conserved throughout evolution. Using the invertebrate Hirudo verbana (Annelida, Hirudinea) as an experimental model, we show here that the RNASET2 ribonuclease is directly involved in the immune response against Gram-positive bacteria. Injection of lipoteichoic acid (LTA), a key component of Gram-positive bacteria cell wall, into the leech body wall induced a massive migration of granulocytes and macrophages expressing TLR2 (the key receptor involved in the response to Gram-positive bacteria) toward the challenged/inoculated area. We hypothesized that the endogenous leech RNASET2 protein (HvRNASET2) might be involved in the antimicrobial response, as already described for other vertebrate ribonucleases, such as RNase3 and RNase7. In support of our hypothesis, HvRNASET2 was mainly localized in the granules of granulocytes, and its release in the extracellular matrix triggered the recruitment of macrophages toward the area stimulated with LTA. The activity of HvRNASET2 was also evaluated on Staphylococcus aureus living cells by means of light, transmission, and scanning electron microscopy analysis. HvRNASET2 injection triggered the formation of S. aureus clumps following a direct interaction with the bacterial cell wall, as demonstrated by immunogold assay. Taken together, our data support the notion that, during the early phase of leech immune response, granulocyte-released HvRNASET2 triggers bacterial clumps formation and, at the same time, actively recruits phagocytic macrophages in order to elicit a rapid and effective eradication of the infecting microorganisms from inoculated area.
SugarMate

Inferring abnormal glucose events such as hyperglycemia and hypoglycemia is crucial for the health of both diabetic patients and non-diabetic people. However, regular blood glucose monitoring can be invasive and inconvenient in everyday life. We present SugarMate, a first smartphone-based blood glucose inference system as a temporary alternative to continuous blood glucose monitors (CGM) when they are uncomfortable or inconvenient to wear. In addition to the records of food, drug and insulin intake, it leverages smartphone sensors to measure physical activities and sleep quality automatically. Provided with the imbalanced and often limited measurements, a challenge of SugarMate is the inference of blood glucose levels at a fine-grained time resolution. We propose Md3RNN, an efficient learning paradigm to make full use of the available blood glucose information. Specifically, the newly designed grouped input layers, together with the adoption of a deep RNN model, offer an opportunity to build blood glucose models for the general public based on limited personal measurements from single-user and grouped-users perspectives. Evaluations on 112 users demonstrate that Md3RNN yields an average accuracy of 82.14%, significantly outperforming previous learning methods those are either shallow, generically structured, or oblivious to grouped behaviors. Also, a user study with the 112 participants shows that SugarMate is acceptable for practical usage.
Usees

HCI has developed a powerful vocabulary for thinking about, and methods for engaging with, users. Similarly, recent work has advanced complementary understanding of technology non-use. However, other spaces of interaction with technology may occur that sit uncomfortably between these two poles. This paper presents two case studies highlighting individuals who neither are clearly users of a system nor are clearly non-users. Based on these cases, the paper develops the concept of usee to help account for such situations that lie between existing analytic categories.
The Transcriptional Cofactor VGLL1 Drives Transcription of Human Papillomavirus Early Genes via TEAD1

Although a number of transcription factors have been reported to be involved in HPV gene expression, little is known about the cofactors that support HPV transcription. In this study, we demonstrate that the transcriptional cofactor VGLL1 plays a prominent role in HPV early gene expression, dependent on its association with the transcription factor TEAD1. Whereas TEAD1 is ubiquitously expressed in a variety of tissues, VGLL1 displays tissue-specific expression and is implicated in the development and differentiation of epithelial lineage tissues, where HPV gene expression occurs. Our results suggest that VGLL1 may contribute to the epithelial specificity of HPV gene expression, providing new insights into the mechanisms that regulate HPV infection. Further, VGLL1 is also critical for the growth of cervical cancer cells and may represent a novel therapeutic target for HPV-associated cancers. ABSTRACT The TEAD family of transcription factors requires associating cofactors to induce gene expression. TEAD1 is known to activate the early promoter of human papillomavirus (HPV), but the precise mechanisms of TEAD1-mediated transactivation of the HPV promoter, including its relevant cofactors, remain unexplored. Here, we reveal that VGLL1, a TEAD-interacting cofactor, contributes to HPV early gene expression. Knockdown of VGLL1 and/or TEAD1 led to a decrease in viral early gene expression in human cervical keratinocytes and cervical cancer cell lines. We identified 11 TEAD1 target sites in the HPV16 long control region (LCR) by in vitro DNA pulldown assays; 8 of these sites contributed to the transcriptional activation of the early promoter in luciferase reporter assays. VGLL1 bound to the HPV16 LCR via its interaction with TEAD1 both in vitro and in vivo. Furthermore, introducing HPV16 and HPV18 whole genomes into primary human keratinocytes led to increased levels of VGLL1, due in part to the upregulation of TEADs. These results suggest that multiple VGLL1/TEAD1 complexes are recruited to the LCR to support the efficient transcription of HPV early genes. IMPORTANCE Although a number of transcription factors have been reported to be involved in HPV gene expression, little is known about the cofactors that support HPV transcription. In this study, we demonstrate that the transcriptional cofactor VGLL1 plays a prominent role in HPV early gene expression, dependent on its association with the transcription factor TEAD1. Whereas TEAD1 is ubiquitously expressed in a variety of tissues, VGLL1 displays tissue-specific expression and is implicated in the development and differentiation of epithelial lineage tissues, where HPV gene expression occurs. Our results suggest that VGLL1 may contribute to the epithelial specificity of HPV gene expression, providing new insights into the mechanisms that regulate HPV infection. Further, VGLL1 is also critical for the growth of cervical cancer cells and may represent a novel therapeutic target for HPV-associated cancers.
The effects of hypoxia and fatigue on skeletal muscle electromechanical delay

What is the central question of this study? What are the mechanisms underlying impaired muscular endurance and accelerated fatigue during acute hypoxia? What is the main finding and its importance? Hypoxia had no effect on the electrochemical latency associated with muscle contraction elicited by supramaximal electrical motor nerve stimulation in vivo. This provides greater insight into the effects of hypoxia and fatigue on the mechanisms of muscle contraction in vivo.
Brazilian version of the European Cross-Cultural Neuropsychological Test Battery (CNTB-BR): diagnostic accuracy across schooling levels

Objective: To translate, establish the diagnostic accuracy, and standardize the Brazilian Portuguese version of the European Cross-Cultural Neuropsychological Test Battery (CNTB) considering schooling level. Methods: We first completed an English-Brazilian Portuguese translation and back-translation of the CNTB. A total of 135 subjects aged over 60 years – 65 cognitively healthy (mean 72.83, SD = 7.71; mean education 9.42, SD = 7.69; illiterate = 25.8%) and 70 with Alzheimer’s disease (AD) (mean 78.87, SD = 7.09; mean education 7.62, SD = 5.13; illiterate = 10%) – completed an interview and were screened for depression. The receiver operating characteristic (ROC) analysis was used to verify the accuracy of each CNTB test to separate AD from healthy controls in participants with low levels of education (≤ 4 years of schooling) and high levels of education (≥ 8 years of schooling). The optimal cutoff score was determined for each test. Results: The Recall of Pictures Test (RPT)-delayed recall and the Enhanced Cued Recall (ECR) had the highest power to separate AD from controls. The tests with the least impact from schooling were the Rowland Universal Dementia Assessment Scale (RUDAS), supermarket fluency, RPT naming, delayed recall and recognition, and ECR. Conclusions: The Brazilian Portuguese version of the CNTB was well comprehended by the participants. The cognitive tests that best discriminated patients with AD from controls in lower and higher schooling participants were RPT delayed recall and ECR, both of which evaluate memory.
Differentiation of Community-Associated and Livestock-Associated Methicillin-Resistant Staphylococcus aureus Isolates and Identification of spa Types by Use of PCR and High-Resolution Melt Curve Analysis

Infections due to methicillin-resistant Staphylococcus aureus (MRSA) are present worldwide and represent a major public health concern. The capability of PCR followed by high-resolution melt (HRM) curve analysis for the detection of community-associated and livestock-associated MRSA strains and the identification of staphylococcal protein A (spa) locus was evaluated in 74 MRSA samples which were isolated from the environment, humans, and pigs on a single piggery. PCR-HRM curve analysis identified four spa types among MRSA samples and differentiated MRSA strains accordingly. ABSTRACT Infections due to methicillin-resistant Staphylococcus aureus (MRSA) are present worldwide and represent a major public health concern. The capability of PCR followed by high-resolution melt (HRM) curve analysis for the detection of community-associated and livestock-associated MRSA strains and the identification of staphylococcal protein A (spa) locus was evaluated in 74 MRSA samples which were isolated from the environment, humans, and pigs on a single piggery. PCR-HRM curve analysis identified four spa types among MRSA samples and differentiated MRSA strains accordingly. A nonsubjective differentiation model was developed according to genetic confidence percentage values produced by tested samples, which did not require visual interpretation of HRM curve results. The test was carried out at different settings, and result data were reanalyzed and confirmed with DNA sequencing. PCR-HRM curve analysis proved to be a robust and reliable test for spa typing and can be used as a tool in epidemiological studies.
Impact of a Telephonic Intervention to Improve Diabetes Control on Health Care Utilization and Cost for Adults in South Bronx, New York

OBJECTIVE Self-management education and support are essential for improved diabetes control. A 1-year randomized telephonic diabetes self-management intervention (Bronx A1C) among a predominantly Latino and African American population in New York City was found effective in improving blood glucose control. To further those findings, this current study assessed the intervention’s impact in reducing health care utilization and costs over 4 years. RESEARCH DESIGN AND METHODS We measured inpatient (n = 816) health care utilization for Bronx A1C participants using an administrative data set containing all hospital discharges for New York State from 2006 to 2014. Multilevel mixed modeling was used to assess changes in health care utilization and costs between the telephonic diabetes intervention (Tele/Pr) arm and print-only (PrO) control arm. RESULTS During follow-up, excess relative reductions in all-cause hospitalizations for the Tele/Pr arm compared with PrO arm were statistically significant for odds of hospital use (odds ratio [OR] 0.89; 95% CI 0.82, 0.97; P < 0.01), number of hospital stays (rate ratio [RR] 0.90; 95% CI 0.81, 0.99; P = 0.04), and hospital costs (RR 0.90; 95% CI 0.84, 0.98; P = 0.01). Reductions in hospital use and costs were even stronger for diabetes-related hospitalizations. These outcomes were not significantly related to changes observed in hemoglobin A1c during individuals’ participation in the 1-year intervention. CONCLUSIONS These results indicate that the impact of the Bronx A1C intervention was not just on short-term improvements in glycemic control but also on long-term health care utilization. This finding is important because it suggests the benefits of the intervention were long-lasting with the potential to not only reduce hospitalizations but also to lower hospital-associated costs.
Clomipramine (Anafranil) in Agoraphobia

1 wish to describe briefly the use of clomi­ pramine in the treatment of a small number of agoraphobic patients in the psychiatric out­ patient clinic of the University Hospital of the West Indies in Kingston, Jamaica. In this clinic the clinical load is heavy: one psy­ chiatrist often having to see 35 patients in a single session; and the majority of patients seen have functional psychoses. The time available, therefore, for dealing with patients with neuroses, and the resources for intensive psychotherapy, behaviour therapy or other sophisticated techniques are both very limited. In this setting it became very noticeable that a fairly small group of patients with the agoraphobic syndrome had been attending the cUnic regularly with little or no improve­ ment in their symptoms, which were extremely disabling.
In Vitro MCF-7 Cells Apoptosis Analysis of Carboplatin Loaded Silk Fibroin Particles

Breast cancer ranks as the fifth leading cause of death worldwide. Chemotherapy is commonly used directly or as neo-adjuvant therapy for the management of breast cancer with its attendant adverse effects, underscoring the need to develop biocompatible bioactive compounds for pharmacological applications. The aim of this study is to encapsulate carboplatin (CP) with silk fibroin protein (SF) by using an ionic gelation method as a drug carrier system and assess the apoptotic effect on MCF-7 breast cancer cells during in vitro studies. The characterization of silk fibroin encapsulated carboplatin (SFCP) microparticles was analyzed by FTIR spectrophotometer, SEM, Mastersizer, and biodegradation methods. The encapsulation efficiency and release profile of SFCP microparticles were analyzed by an indirect UV–Vis spectrophotometric method. An apoptotic screening of MCF-7 cells was carried out with 10–200 µg/mL CP loaded SFCP, which were cultured for 24, 48, and 72 h. Data were analyzed using the Student’s t test and analysis of variance. FTIR and drug release studies confirmed an interaction of silk fibroin with the carboplatin moiety. SFCP showed successful encapsulation of the carboplatin moiety. Apoptotic screening showed a dose dependent increase in absorbance, indicating significant cell death (p < 0.05). Thus, the direct apoptotic effect of SFCP microparticles on MCF-7 was confirmed.
Influence of sampling accuracy on augmented reality for laparoscopic image-guided surgery

Abstract Purpose This study aims to evaluate the accuracy of point-based registration (PBR) when used for augmented reality (AR) in laparoscopic liver resection surgery. Material and methods The study was conducted in three different scenarios in which the accuracy of sampling targets for PBR decreases: using an assessment phantom with machined divot holes, a patient-specific liver phantom with markers visible in computed tomography (CT) scans and in vivo, relying on the surgeon’s anatomical understanding to perform annotations. Target registration error (TRE) and fiducial registration error (FRE) were computed using five randomly selected positions for image-to-patient registration. Results AR with intra-operative CT scanning showed a mean TRE of 6.9 mm for the machined phantom, 7.9 mm for the patient-specific phantom and 13.4 mm in the in vivo study. Conclusions AR showed an increase in both TRE and FRE throughout the experimental studies, proving that AR is not robust to the sampling accuracy of the targets used to compute image-to-patient registration. Moreover, an influence of the size of the volume to be register was observed. Hence, it is advisable to reduce both errors due to annotations and the size of registration volumes, which can cause large errors in AR systems.