Improving nonalcoholic fatty liver disease classification performance with latent diffusion models.

Integrating deep learning with clinical expertise holds great potential for addressing healthcare challenges and empowering medical professionals with improved diagnostic tools. However, the need for annotated medical images is often an obstacle to leveraging the full power of machine learning models. Our research demonstrates that by combining synthetic images, generated using diffusion models, with real images, we can enhance nonalcoholic fatty liver disease (NAFLD) classification performance even in low-data regime settings. We evaluate the quality of the synthetic images by comparing two metrics: Inception Score (IS) and Fréchet Inception Distance (FID), computed on diffusion- and generative adversarial network (GAN)-generated images. Our results show superior performance for the diffusion-generated images, with a maximum IS score of 1.90 compared to 1.67 for GANs, and a minimum FID score of 69.45 compared to 100.05 for GANs. Utilizing a partially frozen CNN backbone (EfficientNet v1), our synthetic augmentation method achieves a maximum image-level ROC AUC of 0.904 on a NAFLD prediction task.

Emergency Department Visits From 2014 to 2018 for Head Injuries in Youth Non-Tackle Football Compared With Other Sports.

BACKGROUND: Non-tackle football (ie, flag, touch, 7v7) is purported to be a lower-risk alternative to tackle football, particularly in terms of head injuries. However, data on head injuries in non-tackle football are sparse, particularly among youth participants. PURPOSE: To describe the epidemiology of  emergency department visits for head injuries due to non-tackle football among youth players in the United States and compare the data with basketball, soccer, and tackle football. STUDY DESIGN: Descriptive epidemiology study. METHODS: Injury data from 2014 to 2018 were obtained from the National Electronic Injury Surveillance System database. Injury reports coded for patients aged 6 to 18 years and associated with basketball, football, or soccer were extracted. Data were filtered to include only injuries to the head region, specifically, the head, ear, eyeball, mouth, or face. Football injuries were manually assigned to "non-tackle" or "tackle" based on the injury narratives. Sports & Fitness Industry Association data were used to estimate annual sport participation and calculate annual injury rates per 100,000 participant-years. RESULTS: A total of 26,770 incident reports from 2014 to 2018 were analyzed. For head region injuries in non-tackle football, the head was the most commonly injured body part, followed by the face; the most common diagnosis was a laceration, followed by concussion and internal injury (defined as an unspecified head injury or internal head injury [eg, subdural hematoma or cerebral contusion]). The most common contacting object was another player. The projected national rate of head region injuries was lowest for non-tackle football across the 4 sports. In particular, the projected rate of injuries to the head for non-tackle football (78.0 per 100,000 participant-years) was less than one-fourth the rates for basketball (323.5 per 100,000 participant-years) and soccer (318.2 per 100,000 participant-years) and less than one-tenth the rate for tackle football (1478.6 per 100,000 participant-years). CONCLUSION: Among youth in the United States aged 6 to 18 years who were treated in the emergency department for injuries related to playing non-tackle football, the most common diagnosis for injuries to the head region was a laceration, followed by a concussion. Head region injuries associated with non-tackle football occurred at a notably lower rate than basketball, soccer, or tackle football.

Comparing Recidivism of Sexual and Nonsexual Offenders: The Role of Humanist, Spiritual, and Religious Involvement.

Some research has considered whether faith-informed programs help persons with a previous incarceration navigate a life away from crime. Few studies considered whether offense category moderates this relationship. Building upon studies that found a strong association between a prior sexual conviction and participation in religion in prison, we assess whether time spent in humanist, spiritual, and religious (HSR) programs in prison is associated with reconviction, separately for persons convicted of a sex offense and any other offense. Our results revealed that a higher level of participation in HSR programs was associated with a lower likelihood and rate of reconviction; however, this effect was more pronounced for persons with a prior sexual conviction. Supplementary analyses revealed that the use of religion in an extrinsic manner was beneficial, suggesting this group may look to religion to gain social support and overcome rejection and loneliness. Extrinsic religiosity among other groups, however, was associated with an increased risk of reconviction.

Effect of Annealing Temperature for Ni/AlOx/Pt RRAM Devices Fabricated with Solution-Based Dielectric.

Resistive random access memory (RRAM) devices with Ni/AlOx/Pt-structure were manufactured by deposition of a solution-based aluminum oxide (AlOx) dielectric layer which was subsequently annealed at temperatures from 200 °C to 300 °C, in increments of 25 °C. The devices displayed typical bipolar resistive switching characteristics. Investigations were carried out on the effect of different annealing temperatures for associated RRAM devices to show that performance was correlated with changes of hydroxyl group concentration in the AlOx thin films. The annealing temperature of 250 °C was found to be optimal for the dielectric layer, exhibiting superior performance of the RRAM devices with the lowest operation voltage (<1.5 V), the highest ON/OFF ratio (>104), the narrowest resistance distribution, the longest retention time (>104 s) and the most endurance cycles (>150).

Calcium Microdomain Formation at the Perisynaptic Cradle Due to NCX Reversal: A Computational Study.

It has recently been proposed using a multi-compartmental mathematical model that negatively fixed charged membrane-associated sites constrain the flow of cations in perisynaptic astroglial processes. This restricted movement of ions between the perisynaptic cradle (PsC), principal astroglial processes and the astrocyte soma gives rise to potassium (K+) and sodium (Na+) microdomains at the PsC. The present paper extends the above model to demonstrate that the formation of an Na+ microdomain can reverse the Na+/Ca2+ exchanger (NCX) thus providing an additional source of calcium (Ca2+) at the PsC. Results presented clearly show that reversal of the Na+/Ca2+ exchanger is instigated by a glutamate transporter coupled increase in concentration of cytoplasmic [Na+]i at the PsC, which and instigates Ca2+ influx through the NCX. As the flow of Ca2+ along the astrocyte process and away from the PsC is also constrained by Ca2+ binding proteins, then a Ca2+ microdomain forms at the PsC. The paper also serves to demonstrate that the EAAT, NKA, and NCX represent the minimal requirement necessary and sufficient for the development of a Ca2+ microdomain and that these mechanisms directly link neuronal activity and glutamate release to the formation of localized Na+ and Ca2+ microdomains signals at the PsC. This local source of Ca2+ can provide a previously underexplored form of astroglial Ca2+ signaling.

Potassium and sodium microdomains in thin astroglial processes: A computational model study.

A biophysical model that captures molecular homeostatic control of ions at the perisynaptic cradle (PsC) is of fundamental importance for understanding the interplay between astroglial and neuronal compartments. In this paper, we develop a multi-compartmental mathematical model which proposes a novel mechanism whereby the flow of cations in thin processes is restricted due to negatively charged membrane lipids which result in the formation of deep potential wells near the dipole heads. These wells restrict the flow of cations to "hopping" between adjacent wells as they transverse the process, and this surface retention of cations will be shown to give rise to the formation of potassium (K+) and sodium (Na+) microdomains at the PsC. We further propose that a K+ microdomain formed at the PsC, provides the driving force for the return of K+ to the extracellular space for uptake by the neurone, thereby preventing K+ undershoot. A slow decay of Na+ was also observed in our simulation after a period of glutamate stimulation which is in strong agreement with experimental observations. The pathological implications of microdomain formation during neuronal excitation are also discussed.

Topical Tavaborole in the Treatment of Onychomycosis Complicated by Dermatophytoma: A Post-hoc Assessment of Phase II Subjects.

Dermatophytoma is a little-known, difficult to treat fungal infection that complicates onychomycosis. First described by Roberts and Evans in the late 1990's, dermatophytoma presents as a dense concentration of fungal hyphae within or under the nail plate and is generally white or yellow/brown in color, and linear (streaks) or round (patches) in shape; primary etiologic organisms are dermatophytes. Oral antifungals have limited success in treating dermatophytoma owing to difficulties accessing and penetrating what is hypothesized to be a fungal biofilm. In this respect, dermatophytoma is generally treated with a combination therapy approach, often including both surgical and pharmacologic intervention for improved outcomes. A post-hoc assessment of Phase II tavaborole onychomycosis studies was conducted in order to assess the prevalence of dermatophytoma and outcomes in patients treated with topical tavaborole. Of the 366 subjects enrolled in the Phase II onychomycosis studies, we identified 102 cases of dermatophytoma; 21 of 86 (24.4%) subjects treated with tavaborole were able to achieve complete resolution of dermatophytoma by day 180, while no subjects on vehicle obtained resolution. Similarly, 23 of 86 subjects (26.7%) treated with tavaborole solution had complete resolution of dermatophytoma by day 360, while only 1 of 16 subjects (6.3%) on vehicle obtained resolution. Moreover, 13 of 19 subjects (68.4%) treated with tavaborole solution were able to sustain resolution, while only 6 of 19 (31.6%) had reoccurrence, of dermatophytoma during the 180-day washout period (day 360). We present 5 cases of dermatophytoma identified in Phase II trials that responded in a positive manner following treatment with tavaborole solution for onychomycosis of the great toenail. Although not representative of all subject outcomes, these findings provide insight into the use of topical tavaborole for dermatophytoma, a condition previously thought to respond only to oral or combination therapy.

J Drugs Dermatol. 2018;17(3):347-354.

In vitro efficacy of tavaborole topical solution, 5% after penetration through nail polish on ex vivo human fingernails.

BACKGROUND: Topical antifungal treatments for onychomycosis are applied to clean, unpolished nails for 48 weeks or longer. Patients often wish to mask their infection with nail polish yet there is no evidence to suggest antifungal efficacy in the presence of nail polish. OBJECTIVE: To determine if tavaborole retains the ability to penetrate the nail plate and inhibit fungal growth in the presence of nail polish. METHOD: Tavaborole was applied to human fingernails painted with 2 or 4 coats of nail polish, and unpainted nails in an ex vivo model. Nails were mounted on TurChub® chambers seeded with Trichophyton rubrum and allowed to incubate for 7 days. Antifungal activity was assessed by measuring zones of inhibition. RESULTS AND CONCLUSION: Tavaborole exhibited antifungal activity in all experimental groups. The zones of inhibition of T. rubrum for all experimental groups (2 or 4 coats of polish, unpolished) were greater than infected controls (polished and unpolished), ps < .001. Tavaborole penetrates polished nails and kills T. rubrum in this ex vivo model.

Evaluation of the efficacy and safety of tavaborole topical solution, 5%, in the treatment of onychomycosis of the toenail in adults: a pooled analysis of an 8-week, post-study follow-up from two randomized phase 3 studies.

PURPOSE: The role of topical antifungal agents in the long-term management of toenail onychomycosis is not well established. The current study evaluated durability of clinical benefit of tavaborole topical solution, 5%, for the treatment of toenail onychomycosis. METHODS: We conducted a pooled analysis of 8-week, post-study follow-up (PSFU) data from two phase 3, randomized controlled trials in a subset of patients who experienced complete or almost clear nail (CN) at the end of treatment (week 52); 48 weeks of treatment with once-daily tavaborole compared with placebo in adults with distal subungual onychomycosis was evaluated at week 60. Complete cure (completely CN plus negative mycology) of the target great toenail and treatment success (<10% nail involvement plus negative mycology) were evaluated at week 52 versus week 60. RESULTS: Of the 62 patients who completed the PSFU, complete cure was higher in the tavaborole-treated group versus the vehicle control group (28.6% vs. 7.7%). Additionally, treatment success was 53.1% for the tavaborole group versus 23.1% in the vehicle group. Small sample size entering the PSFU limited robust statistical analysis. CONCLUSION: Tavaborole topical solution, 5%, appears to provide durable clinical benefit, making it an attractive long-term treatment option for dermatophyte-associated onychomycosis of the toenail.

Clinical trial designs for topical antifungal treatments of onychomycosis and implications on clinical practice.

There currently are 3 topical agents approved by the US Food and Drug Administration (FDA) to treat onychomycosis: tavaborole, efinaconazole, and ciclopirox. The phase 3 clinical trial designs for these treatments and their notable differences make it difficult for clinicians to interpret the data into clinical practice. For example, the primary end point predominantly used to assess efficacy in all the trials is complete cure, defined as no involvement of the nail plus mycologic cure; also, a notable number of patients fail to achieve a complete cure despite clear improvement in the nail. Despite close similarities in the end points and overall design of the clinical trials used for these agents, differences in design are notable, including the age range of participants, the range of mycotic nail involvement, the presence/absence of tinea pedis, and the nail trimming/debridement protocols used. The differences in clinical trial designs for the 3 FDA-approved topical agents and the lack of head-to-head studies makes efficacy interpretation and comparison inappropriate. This article reviews the phase 3 clinical trials that led to FDA approval of these agents, focusing on their similarities and differences.

Dispersion relation data for methylammonium lead triiodide perovskite deposited on a (100) silicon wafer using a two-step vapour-phase reaction process.

Ellipsometry was used to measure the amplitude ratio and phase difference of light undergoing a phase shift as it interacts with a thin film of organic-inorganic hybrid perovskite CH3NH3PbI3 (MAPI) deposited onto a (100) silicon wafer. The refractive index and extinction coefficient was extracted from a multi-oscillator model fit to the ellipsometry data, as a function of wavelength, from 300 to 1500 nm.

Silicon-based dynamic synapse with depressing response.

A compact implementation of a dynamic charge transfer synapse cell, capable of implementing synaptic depression, is presented. The cell is combined with a simple current mirror summing node to produce biologically plausible postsynaptic potentials (PSPs). A single charge packet is effectively transferred from the synapse to the summing node, whenever a presynaptic pulse is applied to one of its terminals. The charge packet is "weighted" by a voltage applied to the second terminal of the synapse. A voltage applied to the third terminal determines the charge recovery time in the synapse, which can be adjusted over several orders of magnitude. This voltage determines the paired pulse ratio for the synapse. The fall time of the PSP is also adjustable and is set by the gate voltage of a metal-oxide-semiconductor field-effect transistor operating in subthreshold. Results extracted from chips fabricated in a 0.35-µm complementary metal-oxide-semiconductor process, alongside theoretical and simulation results, confirm the ability of the cell to produce PSPs that are characteristic of real synapses. The concept addresses a key requirement for scalable hardware neural networks.

A generic operational strategy to qualify translational safety biomarkers.

The importance of using translational safety biomarkers that can predict, detect and monitor drug-induced toxicity during human trials is becoming increasingly recognized. However, suitable processes to qualify biomarkers in clinical studies have not yet been established. There is a need to define clear scientific guidelines to link biomarkers to clinical processes and clinical endpoints. To help define the operational approach for the qualification of safety biomarkers the IMI SAFE-T consortium has established a generic qualification strategy for new translational safety biomarkers that will allow early identification, assessment and management of drug-induced injuries throughout R&D.

Building a sustainable system: the making of the WTIS.

Building Ontario's Wait Time Information System (WTIS) was one of the largest and most complex technology projects Cancer Care Ontario (CCO) had ever taken on. Increasing public concern about wait times and the lack of adequate tools to provide a clear or accurate picture of provincial wait times had led to a sense of urgency for the province to report wait time data. While healthcare providers and the Ministry of Health and Long-term Care (MOHLTC) sought to address timely access to care, the challenges to develop a suitable information management/information technology (IM/IT) solution within aggressive timelines were significant. For the WTIS project, success was defined by the ability to deliver a tool to capture wait time data that addressed business and clinical needs and by providing individuals with the ability to use the tool and its data to improve access to care.

Intercessory prayer for the alleviation of ill health.

BACKGROUND: Prayer is amongst the oldest and most widespread interventions used with the intention of alleviating illness and promoting good health. Given the significance of this response to illness for a large proportion of the world's population, there has been considerable interest in recent years in measuring the efficacy of intercessory prayer for the alleviation of ill health in a scientifically rigorous fashion. The question of whether this may contribute towards proving or disproving the existence of God is a philosophical question lying outside the scope of this review of the effects of prayer. This revised version of the review has been prepared in response to feedback and to reflect new methods in the conduct and presentation of Cochrane reviews. OBJECTIVES: To review the effects of intercessory prayer as an additional intervention for people with health problems already receiving routine health care. SEARCH STRATEGY: We systematically searched ten relevant databases including MEDLINE and EMBASE (June 2007). SELECTION CRITERIA: We included any randomised trial comparing personal, focused, committed and organised intercessory prayer with those interceding holding some belief that they are praying to God or a god versus any other intervention. This prayer could be offered on behalf of anyone with health problems. DATA COLLECTION AND ANALYSIS: We extracted data independently and analysed it on an intention to treat basis, where possible. We calculated, for binary data, the fixed-effect relative risk (RR), their 95% confidence intervals (CI), and the number needed to treat or harm (NNT or NNH). MAIN RESULTS: Ten studies are included in this updated review (7646 patients). For the comparison of intercessory prayer plus standard care versus standard care alone, overall there was no clear effect of intercessory prayer on death, with the effect not reaching statistical significance and data being heterogeneous (6 RCTs, n=6784, random-effects RR 0.77 CI 0.51 to 1.16, I(2) 83%). For general clinical state there was also no significant difference between groups (5 RCTs, n=2705, RR intermediate or bad outcome 0.98 CI 0.86 to 1.11). Four studies found no effect for re-admission to Coronary Care Unit (4 RCTs, n=2644, RR 1.00 CI 0.77 to 1.30).Two other trials found intercessory prayer had no effect on re-hospitalisation (2 RCTs, n=1155, RR 0.93 CI 0.71 to 1.22). AUTHORS' CONCLUSIONS: These findings are equivocal and, although some of the results of individual studies suggest a positive effect of intercessory prayer,the majority do not and the evidence does not support a recommendation either in favour or against the use of intercessory prayer. We are not convinced that further trials of this intervention should be undertaken and would prefer to see any resources available for such a trial used to investigate other questions in health care.

Comparative properties of recombinant human and bovine matrix metalloproteinase-20.

INTRODUCTION: Matrix metalloproteinase-20 (MMP-20) is a predominant enzyme for the progressive processing of enamel extracellular matrix protein components (primarily amelogenin) during the early stages of enamel formation. So far, the recombinant porcine, mouse and bovine MMP-20 have been cloned and used extensively in the researches of tooth enamel development. The homology of these MMP-20s to human MMP-20 is approximately 80%. The effect of sequence differences on the properties of these enzymes is poorly understood even though they have been used to hydrolyse amelogenins from different species. OBJECTIVE: Our goal is to compare the characteristics between recombinant human MMP-20 (rhMMP-20) and bovine MMP-20 (rbMMP-20). DESIGN: rhMMP-20 and rbMMP-20 were parallelly expressed, purified and activated. The SDS-PAGE, zymography and quenched peptide assay were used for characterization and comparisons. RESULTS: Both proteases were activated by autocatalysis in a similar pattern of fragmentation. Dynamically, rbMMP-20 autoactivated faster and digested a fluorescence-quenched peptide Mca-PLGL-Dpa-AR, a non-amelogenin substrate, more efficiently than rhMMP-20. However, rhMMP-20 showed higher enzymatic activity for a human amelogenin substrate and in addition, it created an extra cleavage site at its C-terminus. CONCLUSIONS: The differences in their catalytic properties and substrate specificities may be attributed to the sequence divergence of MMP-20 between species, especially in the hinge region.