Miracle-dz/UniFAR-FTUs huggingface dataset:
Lower Signal Intensity of the Anterior Talofibular Ligament is Associated with a Higher Rate of Return to Sport After ATFL Repair for Chronic Lateral Ankle Instability

Background: The treatment strategy for anterior talofibular ligament (ATFL) injury is usually determined by the ATFL remnant condition during surgery. Preoperative magnetic resonance imaging (MRI)–based signal intensity of the ATFL remnant, represented by the signal/noise ratio (SNR) value, can reveal the ATFL remnant condition. Thus far, there is a lack of evidence regarding the relationship between the ATFL remnant condition and functional outcomes. Purpose/Hypothesis: The purpose was to quantitatively evaluate whether the MRI-based ATFL ligament SNR value is related to functional outcomes after ATFL repair for ankles with chronic lateral ankle instability. The hypothesis was that a lower preoperative SNR is related to a better clinical outcome, particularly a higher rate of return to sport. Study Design: Cohort study; Level of evidence, 3. Methods: First, a preliminary study was performed to measure the ATFL SNR in preoperative MRI, the results of which suggested that a preoperative SNR >10.4 was indicative of a poor ATFL condition. Then, a cohort study was retrospectively performed with consecutive patients who underwent open repair of ATFL injuries between January 2009 and August 2014. Accordingly, the patients were divided into 2 groups: high SNR (HSNR; ≥10.4) and low SNR (LSNR; <10.4). Functional outcomes based on the American Orthopaedic Foot and Ankle Society (AOFAS) score, Karlsson Ankle Functional Score (KAFS), and Tegner Activity Scale were then compared between the HSNR group and the LSNR group. Results: Ultimately, 70 patients were available for the final follow-up: 37 in the HSNR group and 33 in the LSNR group. No significant difference was detected between the HSNR group and the LSNR group in terms of the AOFAS score, KAFS, or Tegner Activity Scale (P > .05 for all) preoperatively. At the final follow-up, the mean ± SD AOFAS score in the LSNR group (92 ± 6) was higher than that in the HSNR group (87 ± 12), although no significant difference was detected postoperatively (P = .16). The mean KAFS in the LSNR group (94 ± 7) was significantly higher than that in the HSNR group (88 ± 11) postoperatively (P = .03). At follow-up, the mean Tegner score in the LSNR group (6; range, 3-7) was significantly higher than that in the HSNR group (5; range, 1-8) postoperatively (P = .03). Patients in the LSNR group had a significantly higher percentage of sports participation than those in the HSNR group (91% vs 65%, P = .02) postoperatively. Conclusion: A lower signal intensity in the ATFL ligament based on preoperative MRI is associated with a better clinical outcome, particularly a higher rate of return to sport.
Efficacy and Safety of Esaxerenone (CS-3150) for the Treatment of Type 2 Diabetes with Microalbuminuria: A Randomized, Double-Blind, Placebo-Controlled, Phase II Trial.

BACKGROUND AND OBJECTIVES The progression of kidney disease in some patients with type 2 diabetes mellitus may not be adequately suppressed by renin-angiotensin system inhibitors. Esaxerenone (CS-3150) is a nonsteroidal mineralocorticoid receptor blocker that has shown kidney protective effects in preclinical studies, and it is a potential add-on therapy to treat diabetic kidney disease. This phase 2 study evaluated the efficacy and safety of esaxerenone in Japanese patients with type 2 diabetes mellitus and microalbuminuria. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This multicenter, randomized, double-blind, placebo-controlled trial enrolled 365 hypertensive or normotensive patients with type 2 diabetes mellitus and microalbuminuria (urinary albumin-to-creatinine ratio ≥45 to <300 mg/g creatinine) treated with renin-angiotensin system inhibitor who had eGFR≥30 ml/min per 1.73 m2. Participants were randomized to receive 0.625, 1.25, 2.5, or 5 mg/d esaxerenone or placebo for 12 weeks. The primary end point was the change in urinary albumin-to-creatinine ratio from baseline to week 12 (with last observation carried forward). RESULTS Esaxerenone treatment at 1.25, 2.5, and 5 mg/d significantly reduced urinary albumin-to-creatinine ratio by the end of treatment (38%, 50%, and 56%, respectively) compared with placebo (7%; all P<0.001). The urinary albumin-to-creatinine ratio remission rate (defined as urinary albumin-to-creatinine ratio <30 mg/g creatinine at the end of treatment and ≥30% decrease from baseline) was 21% in the 2.5- and 5-mg/d groups versus 3% for placebo (both P<0.05). Adverse events occurred slightly more frequently with esaxerenone versus placebo, but the frequencies of drug-related adverse events and discontinuation rates were similar in the placebo and the 0.625-, 1.25-, and 2.5-mg/d groups. Drug-related adverse events and treatment discontinuations were marginally higher in the 5-mg/d group. The most common drug-related adverse event was hyperkalemia, which was dose proportional. CONCLUSIONS Adding esaxerenone at 1.25, 2.5, and 5 mg/d for 12 weeks to an ongoing renin-angiotensin system inhibitor significantly reduces urinary albumin-to-creatinine ratio in patients with type 2 diabetes mellitus and microalbuminuria.
Association of Initiation of Maintenance Dialysis with Functional Status and Caregiver Burden.

BACKGROUND AND OBJECTIVES Little is known about the functional course after initiating dialysis in elderly patients with ESKD. The aim of this study was to assess the association of the initiation of dialysis in an elderly population with functional status and caregiver burden. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS This study included participants aged ≥65 years with ESKD who were enrolled in the Geriatric Assessment in Older Patients Starting Dialysis study. All underwent a geriatric assessment and a frailty screening (Fried Frailty Index and Groningen Frailty Indicator) at dialysis initiation. Functional status (activities of daily life and instrumental activities of daily life) and caregiver burden were assessed at baseline and after 6 months. Decline was defined as loss of one or more domains in functional status, stable as no difference between baseline and follow-up, and improvement as gain of one or more domains in functional status. Logistic regression was performed to assess the association between the combined outcome functional decline/death and potential risk factors. RESULTS Of the 196 included participants functional data were available for 187 participants. Mean age was 75±7 years and 33% were women. At the start of dialysis, 79% were care dependent in functional status. After 6 months, 40% experienced a decline in functional status, 34% remained stable, 18% improved, and 8% died. The prevalence of high caregiver burden increased from 23%-38% (P=0.004). In the multivariable analysis age (odds ratio, 1.05; 95% confidence interval, 1.00 to 1.10 per year older at baseline) and a high Groningen Frailty Indicator compared with low score (odds ratio, 1.97; 95% confidence interval, 1.05 to 3.68) were associated with functional decline/death. CONCLUSIONS In patients aged ≥65 years, functional decline within the first 6 months after initiating dialysis is highly prevalent. The risk is higher in older and frail patients. Loss in functional status was mainly driven by decline in instrumental activities of daily life. Moreover, initiation of dialysis is accompanied by an increase in caregiver burden. PODCAST This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_06_27_CJASNPodcast_19_07_. mp3.
Hyaluronic Acid (HA), Platelet-Rich Plasm and Extracorporeal Shock Wave Therapy (ESWT) promote human chondrocyte regeneration in vitro and ESWT-mediated increase of CD44 expression enhances their susceptibility to HA treatment

Novel strategies have been proposed for articular cartilage damage occurring during osteoarthritis (OA) and -among these- Extracorporeal Shock Wave Therapy (ESWT), intra-articular injections of Platelet-Rich Plasma (PRP) or Hyaluronic Acid (HA) revealed encouraging results. To investigate the possible mechanisms responsible for those clinical benefits, we established primary cultures of human chondrocytes derived from cartilage explants and measured the in vitro effects of ESW, PRP and HA therapies. After molecular/morphological cell characterization, we assessed those effects on the functional activities of the chondrocyte cell cultures, at the protein and molecular levels. ESWT significantly prevented the progressive dedifferentiation that spontaneously occurs during prolonged chondrocyte culture. We then attested the efficiency of all such treatments to stimulate the expression of markers of chondrogenic potential such as SOX9 and COL2A, to increase the Ki67 proliferation index as well as to antagonize the traditional marker of chondrosenescence p16INK4a (known as Cdkn2a). Furthermore, all our samples showed an ESW- and HA-mediated enhancement of migratory and anti-inflammatory activity onto the cytokine-rich environment characterizing OA. Taken together, those results suggest a regenerative effect of such therapies on primary human chondrocytes in vitro. Moreover, we also show for the first time that ESW treatment induces the surface expression of major hyaluronan cell receptor CD44 allowing the increase of COL2A/COL1A ratio upon HA administration. Therefore, this work suggests that ESW-induced CD44 overexpression enhances the in vitro cell susceptibility of human chondrocytes to HA, presumably favouring the repair of degenerated cartilage.
Nudging to get our food choices on a sustainable track

Food production is one of the major contributors to environmental damage. Adaptations in our food choices are needed to preserve resources for the needs of future generations. More sustainable consumption patterns have been encouraged by economic incentives, laws, education and communication campaigns. Nonetheless, consumers still find difficulties in trying to change their current food habits. This review takes a behavioural approach in encouraging sustainable food choices among consumers. From a nudging perspective, many behavioural changes can be encouraged in a non-obtrusive way by adapting the complex food environment in which consumers are operating. These interventions do not restrict consumers' choices but rather adapt the choice architecture wherein food decisions are made. Drawing on the literature from diverse theoretical perspectives, we provide an overview of the application of nudging for more sustainable food choices and highlight where more research is needed. More specifically, we discuss research that used nudging to engender cognitive impact (i.e. the use of labels or visibility enhancements), affective responses (i.e. sensorial and social influence cues) and behavioural effects (i.e. adjustments in convenience and product size). We conclude that this review only shows the tip of the iceberg of the research on nudging and sustainable consumption that is likely forthcoming in the next few years, following the successes of nudging applications in other domains. Nonetheless, each individual nudging intervention requires careful examination. Personal predispositions towards the environment should be considered when designing interventions, demonstrating the complementarity of nudging with education on sustainable consumption.
Quaternary Ammonium Leucine-Based Surfactants: The Effect of a Benzyl Group on Physicochemical Properties and Antimicrobial Activity

Quaternary ammonium amphiphiles are a class of compounds with a wide range of commercial and industrial uses. In the pharmaceutical field, the most common quaternary ammonium surfactant is benzalkonium chloride (BAC), which is employed as a preservative in several topical formulations for ocular, skin, or nasal application. Despite the broad antimicrobial activity against Gram-positive and Gram-negative bacteria, as well as fungi and small enveloped viruses, safety concerns regarding its irritant and cytotoxic effect on epithelial cells still remain. In this work, quaternary ammonium derivatives of leucine esters (C10, C12 and C14) were synthesised as BAC analogues. These cationic surfactants were characterised in terms of critical micelle concentration (CMC, by tensiometry), cytotoxicity (MTS and LDH assays on the Caco-2 and Calu-3 cell lines) and antimicrobial activity on the bacterial species Staphylococcus aureus and Enterococcus faecalis among the Gram-positives, Escherichia coli and Pseudomonas aeruginosa among the Gram-negatives and the yeast Candida albicans. They showed satisfactory surface-active properties, and a cytotoxic effect that was dependent on the length of the hydrophobic chain. Lower minimum inhibiting concentration (MIC) values were calculated for C14-derivatives, which were comparable to those calculated for BAC toward Gram-positive bacteria and slightly higher for Gram-negative bacteria and C. albicans. Thus, the synthesised leucine-based quaternary ammonium cationic surfactants can potentially find application as promising surface-active compounds with antimicrobial activity.
C57BL/6 congenic mouse NRASQ61K melanoma cell lines are highly sensitive to the combination of Mek and Akt inhibitors in vitro and in vivo

RAS is frequently mutated in various tumors and known to be difficult to target. NRASQ61K/R are the second most frequent mutations found in human skin melanoma after BRAFV600E. Aside from surgery, various approaches, including targeted therapies, immunotherapies, and combination therapies, are used to treat patients carrying NRAS mutations, but they are inefficient. Here, we established mouse NRASQ61K melanoma cell lines and genetically derived isografts (GDIs) from Tyr::NRASQ61K mouse melanoma that can be used in vitro and in vivo in an immune‐competent environment (C57BL/6) to test and discover novel therapies. We characterized these cell lines at the cellular, molecular, and oncogenic levels and show that NRASQ61K melanoma is highly sensitive to the combination of Mek and Akt inhibitors. This preclinical model shows much potential for the screening of novel therapeutic strategies for patients harboring NRAS mutations that have limited therapeutic options and resulted in poor prognoses.
Targeting PCNA with Peptide Mimetics for Therapeutic Purposes

Proliferating cell nuclear antigen (PCNA) is an excellent inhibition target to shut down highly proliferative cells and thereby develop a broad‐spectrum cancer therapeutic. It interacts with a wide variety of proteins through a conserved motif referred to as the PCNA‐interacting protein (PIP) box. There is large sequence diversity between high‐affinity PCNA binding partners, but with conservation of the binding structure—a well‐defined 310‐helix. Herein, all current PIP‐box peptides crystallised with human PCNA are collated to reveal common trends between binding structure and affinity. Key intra‐ and intermolecular hydrogen‐bonding networks that stabilise the 310‐helix of PIP‐box partners are highlighted and related back to the canonical PIP‐box motif. High correlation with the canonical PIP‐box sequence does not directly afford high affinity. Instead, we summarise key interactions that stabilise the binding structure that leads to enhanced PCNA binding affinity. These interactions also implicate the “non‐conserved” residues within the PIP‐box that have previously been overlooked. Such insights will allow a more directed approach to develop therapeutic PCNA inhibitors.
The antinociceptive effect of artemisinin on the inflammatory pain and role of GABAergic and opioidergic systems

Background Pain is a complex mechanism which involves different systems, including the opioidergic and GABAergic systems. Due to the side effects of chemical analgesic agents, attention toward natural agents have been increased. Artemisinin is an herbal compound with widespread modern and traditional therapeutic indications, which its interaction with the GABAergic system and antinoniceptive effects on neuropathic pain have shown. Therefore, this study was designed to evaluate the antinociceptive effects of artemisinin during inflammatory pain and interaction with the GABAergic and opioidergic systems by using a writhing response test. Methods On the whole, 198 adult male albino mice were used in 4 experiments, including 9 groups (n = 6) each with three replicates, by intraperitoneal (i.p.) administration of artemisinin (2.5, 5, and 10 mg/kg), naloxone (2 mg/kg), bicuculline (2 mg/kg), saclofen (2 mg/kg), indomethacin (5 mg/kg), and ethanol (10 mL/kg). Writhing test responses were induced by i.p. injection of 10 mL/kg of 0.6% acetic acid, and the percentage of writhing inhibition was recorded. Results Results showed significant dose dependent anti-nociceptive effects from artemisinin which, at a 10 mg/kg dose, was statistically similar to indomethacin. Neither saclofen nor naloxone had antinociceptive effects and did not antagonize antinociceptive effects of artemisinin, whereas bicuculline significantly inhibited the antinocicptive effect of artemisinin. Conclusions It seems that antinocicptive effects of artemisinin are mediated by GABAA receptors.
A role for Numb in Protein kinase M (PKM)‐mediated increase in surface AMPA receptors during facilitation in Aplysia

There is considerable evidence from both vertebrates and invertebrates that persistently active protein kinases maintain changes in synaptic strength that underlie memory. In the hermaphrodite marine mollusk, Aplysia californica, truncated forms of protein kinase C (PKC) termed protein kinase Ms have been implicated in both intermediate‐ and long‐term facilitation, an increase in synaptic strength between sensory neurons and motor neurons thought to underlie behavioural sensitization in the animal. However, few substrates have been identified as candidates that could mediate this increase in synaptic strength. PKMs have been proposed to maintain synaptic strength through preventing endocytosis of AMPA receptors. Numb is a conserved regulator of endocytosis that is modulated by phosphorylation. We have identified and cloned Aplysia Numb (ApNumb). ApNumb contains three conserved PKC phosphorylation sites and PKMs generated from classical and atypical Aplysia PKCs can phosphorylate ApNumb in vitro and in cells. Over‐expression of ApNumb that lacks the conserved PKC phosphorylation sites blocks increases in surface levels of a pHluorin‐tagged Aplysia glutamate receptor measured using live imaging after intermediate‐ or long‐term facilitation. Over‐expression of this form of ApNumb did not block increases in synaptic strength seen during intermediate‐term facilitation, but did block increases in synaptic strength seen during long‐term facilitation. There was no effect of over‐expression of this form of ApNumb on other putative Numb targets as measured using increases in calcium downstream of neurotrophins or agonists of metabotropic glutamate receptors. These results suggest that in Aplysia neurons, Numb specifically regulates AMPA receptor trafficking and is an attractive candidate for a target of PKMs in long‐term maintenance of synaptic strength.
Anti-thrombogenic coatings for devices in neurointerventional surgery: Case report and review of the literature

Background: Stent-assisted coiling and extra-saccular flow diversion require dual anti-platelet therapy due to the thrombogenic properties of the implants. While both methods are widely accepted, thromboembolic complications and the detrimental effects of dual anti-platelet therapy remain a concern. Anti-thrombogenic surface coatings aim to solve both of these issues. Current developments are discussed within the framework of an actual clinical case. Case description: A 33-year-old male patient lost consciousness while doing sport and was administered 500 mg acetylsalicylic acid on site. Computed tomography revealed a massive subarachnoid haemorrhage, and digital subtraction angiography showed an aneurysm of the right middle cerebral artery. Stent-assisted coiling using a neck bridging device with a hydrophilic coating (pCONUS_HPC) was considered as an appropriate approach. Another 500 mg acetylsalicylic acid IV was given. After the single anti-platelet therapy was seen to be effective, a pCONUS_HPC was implanted, and the aneurysm sac subsequently fully occluded using coils. No thrombus formation was encountered. During the following days, 2 × 500 mg acetylsalicylic acid IV daily were required to maintain single anti-platelet therapy, monitored by frequent response testing. Follow-up digital subtraction angiography after 13 days confirmed the occlusion of the aneurysm and the patency of the middle cerebral artery. Conclusion: A variety of ways to reduce the thrombogenicity of neurovascular stents is discussed. Hydrophilic surface coatings are a valid concept to improve the haemocompatibility of neurovascular implants while avoiding the use of dual anti-platelet therapy. Phosphorylcholine and phenox hydrophilic polymer coating are currently the most promising candidates. This concept is supported by anecdotal experience. However, formalised registries and randomised trials are currently being established.
Improvement of left ventricular function after percutaneous coronary intervention in patients with stable coronary artery disease and preserved ejection fraction: Impact of diabetes mellitus

Background Many patients with stable coronary artery disease (CAD) have no visual segmental wall motion abnormalities and a left ventricular (LV) ejection fraction (LVEF) ≥ 50% at rest despite significant coronary artery stenosis. Here, the aim was to determine the impact of percutaneous coronary intervention (PCI) on LV function assessed by enhanced echocardiography in patients with stable CAD with or without diabetes mellitus type 2 and a preserved LVEF. Methods Sixty-six consecutive patients with CAD and LVEF ≥ 50%, admitted to the hospital for planned coronary angiography, were prospectively assessed. PCI was performed for coronary artery stenosis > 70%. CAD extent was assessed using SYNTAX and EXTENT scores. To assess LV function, LVEF, global longitudinal strain (GLS), and LV peak systolic myocardial velocity (S′) were measured and Tei index was calculated before and 3 months after PCI. Results Before PCI, LVEF, GLS, and Tei index were significantly worse in diabetic patients. LV functional indices improved significantly after PCI in all patients (p < 0.001). Multivariate linear regression analyses were performed to evaluate the impact of selected factors on LV function after PCI expressed as changes (Δ) of LVEF, GLS, S′, and Tei index. LV function improvement expressed as ΔGLS was associated only with SYNTAX score. Higher SYNTAX scores were related to greater GLS improvement (β = 0.003, 95% confidence interval: 0.0004–0.005; p = 0.02). Conclusions Percutaneous coronary intervention significantly improved LV function in diabetic and non-diabetic CAD patients with preserved LVEF. Enhanced echocardiography allowed an assessment of subtle changes in LV function.
Android Malicious Behavior Detection Based on Sensitive API Monitoring

A two-step model combining static permission filtering and sensitive API monitoring has been proposed for android malicious behavior analysis. Permission filtering matrix is used to determine whether an application has potential risks. And sensitive API monitoring, based on the reverse engineering, can monitor those sensitive APIs such as sending SMS, accessing user location, device ID, phone number, etc. From experiments, it shows that our proposed method is feasible and effective for monitoring this kind of malicious behavior.