Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of Bead-Based Assays for the Isolation of Foodborne Viruses from Low-Moisture Foods.

ABSTRACT Foodborne viruses such as norovirus and hepatitis A virus (HAV) are highly transmissible, persistent in the environment, and resistant to many conventional inactivation methods. Foods can become contaminated with these viruses either at the source of harvest or during food handling and processing. Multiple lines of evidence suggest that foodborne viruses can survive desiccation and dry conditions. Several foodborne virus outbreaks have been linked to low-moisture foods (LMFs), indicating that these foods can be vehicles of virus transmission. However, the efficiencies of common virus extraction methodologies have not been examined with LMFs. We adapted the International Organization for Standardization (ISO) 15216-1:2017 method for virus recovery for use with chocolate, pistachios, and cornflakes. We also developed a magnetic bead assay for the recovery of HAV from LMFs and used the porcine gastric mucin-coated magnetic beads (PGM-MBs) to extract norovirus surrogates, feline calicivirus (FCV), and murine norovirus (MNV) from the same LMFs. The efficiency of virus recovery using the bead-based assay was then compared with that of the ISO 15216-1:2017 method. In chocolate and pistachios, the recovery rates with the PGM-MB method were 5.6- and 21.3-fold higher, respectively, for FCV and 1.65- and 18-fold higher, respectively, for MNV than those with the ISO 15216-1:2017 method. However, the PGM-MB method failed to recover MNV and FCV from cornflakes. The recovery rates for HAV in chocolate, pistachios, and corn flakes with the magnetic bead method were 11.5-, 3-, and 5.6-fold higher, respectively, than those with the ISO 15216-1:2017 method. Thus, depending upon the food matrix and the target virus, the bead-based assays can be used to efficiently and rapidly extract viruses from LMFs. HIGHLIGHTS
Structural Stability Predicts the Binding Mode of Protein-Ligand Complexes

The prediction of a ligand's binding mode into its macromolecular target is essential in structure-based drug discovery. Even though a tremendous effort has been made to address this problem, most of the tools developed work in a similar way, trying to predict the binding free energy associated with each particular binding mode. In this study we decided to abandon this criterium, following structural stability instead. This view, implemented in a novel computational workflow, quantifies the steepness of the local energy minimum associated to each potential binding mode. Surprisingly, the protocol outperforms docking scoring functions in case of fragments (ligands with MW < 300Da) and is as good as docking for drug-like molecules. It also identifies substructures that act as structural anchors, predicting their binding mode with particular accuracy. The results open a new physical perspective for binding mode prediction, which can be combined with existing thermodynamic-based approaches.
A Game-Based, Physical Activity Coaching Application for Older Adults: Design Approach and User Experience in Daily Life.

Objectives: In this article, we describe the design approach of a game-based, mobile coaching application for older adults (65-75 years) that aimed to stimulate physical activity (PA) in daily life. We evaluated older adults' experiences using this application compared with a standard coaching application in terms of engagement, motivation to be physically active, and in relation to the applied design features. Development and Design: An iterative design approach was followed to develop the game-based coaching application, called WordFit. Step count data (FitBit) were used for the crossword-inspired game. The standard coaching application (the ActivityCoach) displayed FitBit data. Materials and Methods: Participants were asked to use the ActivityCoach for 1 week first and then use WordFit for up to 3 weeks. Engagement was determined by logging actual use and motivation for PA by a daily in-app motivation question and step count data. Afterward, a semistructured interview was conducted. Results: Twenty older adults participated (71.0 ± 5.0 years). Of these, 16/20 actively used the ActivityCoach (13.1 ± 10.0 days) and 8/20 used WordFit (14.8 ± 9.5 days). For the latter, mean PA before WordFit use was 5852 ± 3652 steps/day, while mean PA using WordFit was 7236 ± 3335 steps/day. The interviews (n = 12) showed that step data and feedback on performance through the ActivityCoach/FitBit were prominent motivators for PA. WordFit was generally played as a stand-alone brain trainer. Cognitive challenge, in-game challenges, and challenges through emergent gameplay were important for engagement to use the game. Older adults did not play WordFit together. Discussion: WordFit was not seen as a tool to help improve PA behavior. Enjoyment of the game concept could be improved by providing older adults with new and nontraditional gaming concepts before assessing game preferences. Follow-up studies should be conducted in a target group that is known for low adherence rates and that can benefit from the intervention provided.
d-chiro-Inositol Ribophostin: A Highly Potent Agonist of d-myo-Inositol 1,4,5-Trisphosphate Receptors: Synthesis and Biological Activities

Analogues of the Ca2+-releasing intracellular messenger d-myo-inositol 1,4,5-trisphosphate [1, Ins(1,4,5)P3] are important synthetic targets. Replacement of the α-glucopyranosyl motif in the natural product mimic adenophostin 2 by d-chiro-inositol in d-chiro-inositol adenophostin 4 increased the potency. Similar modification of the non-nucleotide Ins(1,4,5)P3 mimic ribophostin 6 may increase the activity. d-chiro-Inositol ribophostin 10 was synthesized by coupling as building blocks suitably protected ribose 12 with l-(+)-3-O-trifluoromethylsulfonyl-6-O-p-methoxybenzyl-1,2:4,5-di-O-isopropylidene-myo-inositol 11. Separable diastereoisomeric 3-O-camphanate esters of (±)-6-O-p-methoxy-benzyl-1,2:4,5-di-O-isopropylidene-myo-inositol allowed the preparation of 11. Selective trans-isopropylidene deprotection in coupled 13, then monobenzylation gave separable regioisomers 15 and 16. p-Methoxybenzyl group deprotection of 16, phosphitylation/oxidation, then deprotection afforded 10, which was a full agonist in Ca2+-release assays; its potency and binding affinity for Ins(1,4,5)P3R were similar to those of adenophostin. Both 4 and 10 elicited a store-operated Ca2+ current ICRAC in patch-clamped cells, unlike Ins(1,4,5)P3 consistent with resistance to metabolism. d-chiro-Inositol ribophostin is the most potent small-molecule Ins(1,4,5)P3 receptor agonist without a nucleobase yet synthesized.
A randomized controlled trial on the impact of healing time on wound healing following ridge preservation using a 70/30% combination of mineralized and demineralized freeze-dried bone allograft.

BACKGROUND To compare the histologic difference in healing between ridge preservation sites treated with a combination allograft of 70% mineralized and 30% demineralized freeze-dried bone allograft (FDBA) evaluated at 8 to 10 weeks versus 18 to 20 weeks post-extraction. Changes in morphological ridge dimensions were also evaluated. MATERIALS AND METHODS Forty-four patients with a single-rooted tooth to be extracted and replaced by a dental implant were recruited for this study. At time of extraction, measurements were taken with a custom acrylic stent, and the extraction socket was grafted with the combination allograft and covered with a nonresorbable membrane. Patients were randomly assigned to the short-term (8 to 10 weeks) or long-term (18 to 20 weeks) healing group. Sites were re-entered for study measurements, a bone core sample, and implant placement. Bone cores obtained during implant placement were analyzed histologically to determine percentages of vital bone, residual graft, and CT/other. RESULTS Thirty-eight of the 44 patients completed the study, 19 in each group. There was a significant difference between the two groups for mean percent vital bone formation (short-term = 18.17%, long-term = 40.32%, p = <.0001) and percentage of residual graft (short-term = 41.54%, long-term = 23.59%, p = <.0001). There was no difference in morphological changes between the two groups. CONCLUSION Ridge preservation using combination FDBA resulted in approximately twice as much vital bone and half as much residual graft material after 18 to 20 weeks of healing compared to only 8 to 10 weeks healing. This article is protected by copyright. All rights reserved.
Section of the Balance Evaluation Systems Test (BESTest) Cutoff Values for Walking Speed Level in Older Women With Hip Fracture

Background and Purpose: Hip fracture is a common injury in older adults, with a high proportion of hip fractures affecting women. After a hip fracture, the recovery of the patient's walking speed is very important; one of the key determinants of walking speed is balance. The Balance Evaluation Systems Test (BESTest), a clinical balance measure, categorizes balance into 6 postural control systems. However, the relationship between the walking speed level and the sections of the BESTest has not been explored for older women with hip fracture. Our objective was to establish section scores for the BESTest cutoff values for walking speed in older women with hip fracture. Methods: This was an observational study involving 46 older women 65 years or older with hip fracture. The BESTest was administered to all participants upon their discharge from the hospital. Participants were divided into groups on the basis of their walking speed levels, and receiver operating characteristic curves were determined for each section of the BESTest. We calculated the cutoff value, area under the curve (AUC), sensitivity, and specificity of each. Results: Section IV-Stability in Gait showed the highest AUC (0.92) compared with the other sections, and the cutoff value determined for the fast and slow walker groups was 64.3% (sensitivity = 0.82, specificity = 0.83). The sections with moderate AUC (0.7-0.9) were I-Biomechanical Constraints (cutoff = 70.0%), III-Anticipatory Postural Adjustments (cutoff = 66.5%), IV-Postural Responses (cutoff = 69.4%), and V-Sensory Orientation (cutoff = 83.4%). The sections with the highest sensitivity (0.82) were I-Biomechanical Constraints and VI-Stability in Gait, and that with the highest specificity (0.88) was II-Stability Limits and Verticality. Conclusions: Five of the BESTest sections (I-Biomechanical Constraints, III-Anticipatory Postural Adjustments, IV-Postural Responses, V-Sensory Orientation, and IV-Stability in Gait) were able to differentiate between fast and slow walkers among older women with hip fracture. Balance during gait and anticipatory postural adjustments were shown to be important components of balance, and their cutoff values were indicators of the balance required to reach fast walking levels.
Laparoscopic hepatectomy in a patient with uncontrolled polycythaemia vera

This case report describes the peri‐operative course of a patient with uncontrolled polycythaemia vera who underwent a laparoscopic hepatectomy for intrahepatic cholangiocarcinoma. Polycythaemia vera is a chronic condition that results in erythrocytosis and puts patients at risk of peri‐operative complications including thrombotic events and paradoxical haemorrhage. Little evidence exists on the ideal peri‐operative management of uncontrolled polycythaemia vera when the proposed procedure carries a high risk of haemorrhage. Our patient presented with a pre‐operative haemoglobin of 197 g.l−1 (haematocrit 65%) and was not phlebotomised pre‐operatively. Intra‐operatively he lost 2700 ml of blood, reducing his haematocrit to 48%, and then suffered fatal thrombotic complications postoperatively. The patient did not receive any blood product transfusions during his peri‐operative course. We review the available evidence to guide the peri‐operative management of patients with polycythaemia vera. The inherent risks of thrombosis and haemorrhage associated with polycythaemia vera need to be weighed against the specific surgical and transfusion‐related risks. Phlebotomy to achieve a pre‐operative haematocrit under 45% is recommended and intra‐operative phlebotomy shows promise for reducing blood loss during hepatectomies. Management of postoperative erythrocytosis may be an important and underappreciated aspect of reducing the peri‐operative risk of thrombosis in patients with polycythaemia vera.
Carvedilol Diminishes Cardiac Remodeling Induced by High-Fructose/High-Fat Diet in Mice via Enhancing Cardiac β-Arrestin2 Signaling

Background: Insulin resistance (IR) is a well-known risk factor for cardiovascular complications. This study aimed to investigate the effect of a dietary model of IR in mice on cardiac remodeling, cardiac β-arrestin2 signaling, and the protective effects of carvedilol as a β-arrestin–biased agonist. Methods and Results: Insulin resistance was induced by feeding mice high-fructose/high-fat diet (HFrHFD) for 16 weeks. Carvedilol was adiministered for 4 weeks starting at week 13. At the end of the experiment, body weight, heart weight, left and right ventricular thickness, visceral fat weight, fasting blood glucose (FBG), serum insulin, IR index, and serum endothelin-1 were measured. In addition, cardiac tissue samples were histopathologically examined. Also, cardiac levels of cardiotrophin-1, β-arrestin2, phosphatidylinositol 4,5 bisphosphate (PIP2), diacylglycerol (DAG), and phosphoserine 473 Akt (pS473 Akt) were measured. Results showed significant increases in the FBG, serum insulin, IR index, serum endothelin-1, cardiac DAG, cardiac fibrosis, and degenerated cardiac myofibrils in HFrHFD-fed mice associated with a significant reduction in cardiac levels of cardiotrophin-1, β-arrestin2, PIP2, and pS473 Akt. On the other hand, carvedilol significantly reduced the heart weight, FBG, serum insulin, IR index, serum endothelin-1, cardiac DAG, left ventricular thickness, right ventricular fibrosis, and degeneration of cardiac myofibrils. In addition, carvedilol significantly increased cardiac levels of cardiotrophin-1, β-arrestin2, PIP2, and pS473 Akt. Conclusion: Carvedilol enhances cardiac β-arrestin2 signaling and reduces cardiac remodeling in HFrHFD-fed mice.
CrossTalk proposal: Barometric pressure, independent of PO2 , is the forgotten parameter in altitude physiology and mountain medicine

The equivalent air altitude model, often employed in altitude medicine research and interventional settings, stipulates that different combinations of barometric pressure (PB) and O2 fraction that produce the same partial pressure of O2 (PO2 ) result in similar physiological responses (Conkin & Wessel, 2008). One could thus assume that normobaric hypoxia (NH) at the same PO2 might serve as a surrogate for hypobaric hypoxia (HH). However, an ever-growing body of evidence challenges this assumption by indicating numerous differences in physiological responses between NH and
The role of emotion regulation and core autism symptoms in the experience of anxiety in autism

Youth with autism spectrum disorder are at elevated risk for impaired emotion regulation and clinically impairing anxiety. A prior developmental framework posited that impaired emotion regulation leads to co-occurring psychiatric conditions such as anxiety, with outcome determined in part by autism spectrum disorder–specific moderating factors. Using measures developed and validated in autism spectrum disorder, this study evaluated (1) the association between emotion regulation and anxiety in a large, community-based sample of youth with autism spectrum disorder and a wide range of intellectual and verbal abilities and (2) whether greater core autism spectrum disorder symptoms strengthened the association between impaired emotion regulation and anxiety. Parents of 1107 children with a community diagnosis of autism spectrum disorder (881 boys; age 6–17 years) participated in an online survey assessing their child’s emotion regulation, anxiety, and autism spectrum disorder symptoms. Emotion regulation impairment significantly predicted whether participants had elevated levels of anxiety, after controlling for demographic variables and autism spectrum disorder symptoms; however, there was no interaction of emotion regulation and autism spectrum disorder symptoms. This study is the first to support the anxiety–emotion regulation association with measures developed and validated specifically for autism spectrum disorder, in a large sample with co-occurring intellectual disability and minimally verbal youth with autism spectrum disorder. Lay abstract Many children with autism spectrum disorder have problems with managing their emotions (emotion regulation) and anxiety. In this study, over 1000 parents completed an online survey which showed that emotion regulation and anxiety are closely linked. Although emotion regulation and anxiety are inter-connected, the results also show that autism symptoms play an important role in anxiety in autism spectrum disorder. Emotion regulation problems may be an important target for the treatment of anxiety in autism.
Is “Dilator Use” More Effective Than “Finger Use” in Exposure Therapy in Vaginismus Treatment?

Abstract Vaginismus is the persistence of difficulties in allowing the vaginal entry of a penis, a finger or a gynecologic examination. This study aimed to compare the success rates of vaginismus therapy with exposure therapy treatment using a finger or a dilator. The finger training group (FTG) (n = 30) and the dilator training group (DTG) (n = 30) were established. Groups were trained about dilatation and desensitization. The Female Sexual Function Index (FSFI) was applied. From the baseline measurement to the post-treatment measurement, the average change in FSFI scores for both groups was statistically significant (p < 0.001). There was a significant difference between two groups in terms of patient drop-out numbers (p = 0.016); the DTG was more successful in continuing treatment than the FTG. This research revealed that DTG is more successful in treatment continuity and show more improvement in sexual functions.
A Bispecific Inhibitor of the EGFR/ADAM17 Axis Decreases Cell Proliferation and Migration of EGFR-Dependent Cancer Cells

Dysregulated epidermal growth factor receptor (EGFR) is an oncogenic driver of many human cancers, promoting aberrant cell proliferation, migration, and survival. Pharmacological targeting of EGFR is often challenged by acquired mechanisms of resistance. Ligand-dependent mechanisms in EGFR wild-type cells rely on ligand or receptor overexpression, allowing cells to outcompete inhibitors and perpetuate signaling in an autocrine manner. Importantly, EGFR ligands are synthesized as membrane-bound precursors that must be solubilized to enable receptor-ligand interactions. The A disintegrin and metalloproteinase 17 (ADAM17) is considered the main sheddase of several EGFR ligands, and a potential pharmacological target. However, its broad substrate range and ubiquitous expression complicate its therapeutic targeting. Here, we present a novel bispecific fusion protein construct consisting of the inhibitory prodomain of ADAM17 (TPD), fused to an EGFR-targeting designed ankyrin repeat protein (DARPin). TPD is a natural inhibitor of ADAM17, maintaining the protease in a zymogen-like form. Meanwhile, the high affinity anti-EGFR DARPin E01 binds to EGFR and inhibits ligand binding. The resulting fusion protein E01-GS-TPD retained binding ability to both molecular targets EGFR and ADAM17. The large difference in affinity for each target resulted in enrichment of the fusion protein in EGFR-positive cells compared to EGFR-negative cells, suggesting a possible application in autocrine signaling inhibition. Accordingly, E01-GS-TPD decreased migration and proliferation of EGFR-dependent cell lines with no significant increase in apoptotic cell death. Finally, inhibition of proliferation was observed through EGFR ligand-dependent mechanisms as growth inhibition was not observed in EGFR mutant or KRAS mutant cell lines. The use of bispecific proteins targeting the EGFR/ADAM17 axis could be an innovative strategy for the treatment of EGFR-dependent cancers.
Systematic Analysis of Monoterpenes: Advances and Challenges in the Treatment of Peptic Ulcer Diseases

Peptic ulcer disease (PUD) is a multifactorial and complex disease caused by an imbalance of protective and aggressive factors (endogenous and exogenous). Despite advances in recent years, it is still responsible for substantial mortality and triggering clinical problems. Over the last decades, the understanding of PUD has changed a lot with the discovery of Helicobacter pylori infection. However, this disease continues to be a challenge due to side-effects, incidence of relapse from use of various anti-ulcer medicines, and the rapid appearance of antimicrobial resistance with current H. pylori therapies. Consequently, there is the need to identify more effective and safe anti-ulcer agents. The search for new therapies with natural products is a viable alternative and has been encouraged. The literature reports the importance of monoterpenes based on the extensive pharmacological action of this class, including wound healing and anti-ulcerogenic agents. In the present study, 20 monoterpenes with anti-ulcerogenic properties were evaluated by assessing recent in vitro and in vivo studies. Here, we review the anti-ulcer effects of monoterpenes against ulcerogenic factors such as ethanol, nonsteroidal anti-inflammatory drugs (NSAIDs), and Helicobacter pylori, highlighting challenges in the field.
Impacts of environmental heterogeneity on natural selection in a wild bird population *

Natural selection has been studied for several decades, resulting in the computation of thousands of selection estimates. Although the importance of environmental conditions on selection has often been suggested, published estimates rarely take into account the effects of environmental heterogeneity on selection patterns. Here, we estimated linear and nonlinear viability selection gradients on morphological traits of 12‐day old nestlings in a wild population of tree swallows (Tachycineta bicolor) across a large‐scale heterogeneous study system in southern Québec, Canada. We assessed the environmental drivers of nestling survival and evaluated their effects on strength and direction of selection gradients. Separate analyses of environmental variables showed that high temperatures and heavy rainfall caused stronger positive linear selection on morphological traits. Weaker linear selection was also measured in more extensively cultivated areas. Both strength and shape of nonlinear quadratic and correlational components of selection were modified by environmental variables. Considering all environmental variables revealed that precipitation since hatching affected patterns of linear selection on traits, while temperatures since hatching shaped nonlinear selection patterns. Our study underlines the importance of quantifying linear and nonlinear natural selection under various environmental conditions and how the evolutionary response of traits may be affected by ongoing human‐induced environmental changes.