3D track extraction from a fluorescent nuclear track detector via machine learning and an application to diagnostics of laser-driven ions.

We have developed an ion diagnostic method for laser-driven ion acceleration experiments that uses fluorescent nuclear track detectors (FNTDs). An FNTD records the particle tracks as color centers and does not require chemical etching, unlike CR-39 track detectors. The color centers are observed using a confocal laser microscope, and 3D particle tracks can be obtained by changing its focal position. The intensity of the color centers corresponds to the energy deposited by the ions. The nuclides of the ions can be determined from the intensity distribution of the color centers as a function of depth and the distance between the stopping point and the surface of the detector. To extract the intensity distribution, we must track the same ion tracks in the depth-layered microscopic images from the surface to the stopping point, even if they overlap with those of other ions. In addition, since an FNTD is sensitive not only to ions but also to electrons and photons, we must identify ion tracks among those from the latter particles. To analyze a statistical number of ion tracks, it is necessary to automate these processes. We have thus developed a method for automated ion detection and 3D tracking that relies on a support vector classifier and a kernelized correlation filter. This method was tested on a laser ion acceleration experiment performed using the J-KAREN-P laser. The method automatically detects ion tracks on FNTDs and tracks them in the depth direction. The training data are sampled from the Heavy-Ion Medical Accelerator in Chiba.

[Relationship between clopidogrel resistance and genetic variability in Kawasaki disease children with coronary artery lesions].

Objective: To analyze the distribution of clopidogrel metabolism-related gene variability in Kawasaki disease (KD) children with coronary artery lesions (CAL) across different age groups and the impact of genetic variability on the efficacy of clopidogrel antiplatelet therapy. Methods: A retrospective cohort study was conducted. Clinical data were collected from 46 KD children with CAL who were hospitalized in the Cardiovascular Center of Children's Hospital of Fudan University between January 2021 and August 2022 and were treated with clopidogrel, including gender, age, body mass index, course of KD, CAL severity grade, and baseline platelet count. According to their age, the children were divided into ≥2-year-old group and <2-year-old group. Their platelet responsiveness was assessed by adenosine diphosphate-induced platelet inhibition rate (ADPi) calculated via thromboelastography, and children were categorized into high on-treatment platelet reactivity (HTPR) and normal on-treatment platelet reactivity (NTPR) groups. Genotypes of CYP2C19, PON1 and ABCB1 were detected. The t test, one-way analysis of variance and Chi-square test were used for intergroup comparison. Results: Among the 46 KD children with CAL, 34 were male and 12 were female; 37 were ≥2-year-old and 9 were <2-year-old; 25 cases were in the HTPR group and 21 cases were in the NTPR group, with 19 HTPR and 18 NTPR in the ≥2-year-old group, and 6 HTPR and 3 NTPR in the <2-year-old group. Genetic analysis showed that 92 alleles among the 46 children, with frequencies of CYP2C19*1, CYP2C19*2, CYP2C19*3, CYP2C19*17, PON1 192Q, PON1 192R, ABCB1 3435C, ABCB1 3435T at 59% (54/92), 32% (29/92), 9% (8/92), 1% (1/92), 36% (36/92), 64% (59/92), 63% (58/92) and 37% (34/92), respectively. Analysis of the impact of genotype on ADPi revealed that in children aged ≥2 years, those with CYP2C19*1/*3 genotype had significantly lower ADPi than those with CYP2C19*1/*1 genotype ((34±15)% vs. (61±29)%, t=2.18, P=0.036). There were also no significant difference in ADPi among children with PON1 192Q homozygous, PON1 192R heterozygote and PON1 192R homozygous genotypes ((40±22)% vs. (52±33)% vs. (65±27)%, F=2.17, P=0.130), or among those with ABCB1 3435C homozygous, ABCB1 3435T heterozygote and ABCB1 3435T homozygous genotypes ((55±34)% vs. (60±27)% vs. (49±24)%, F=0.33, P=0.719). In <2-year-old group, there were no significant differences in ADPi across CYP2C19*1/*1, CYP2C19*1/*2 and CYP2C19*2*2 genotypes ((40±20)% vs. (53±37)% vs. (34±16)%, F=0.37, P>0.05). There were no significant differences in ADPi across CYP2C19*1/*1 and CYP2C19*1/*3 genotypes ((44±27)% vs. (42±20)%, t=0.08, P>0.05). There were no significant differences in ADPi across PON1 192Q homozygous, PON1 192R heterozygote and PON1 192R homozygous genotypes (45% vs. (55±27)% vs. (24±5)%, F=1.83, P>0.05). There were no significant differences in ADPi across ABCB1 3435C homozygous, ABCB1 3435T heterozygote and ABCB1 3435T homozygous genotypes ((36±16)% vs. (50±35)% vs. 45%, F=0.29, P>0.05). The risk analysis of HTPR in different genotypes revealed that in children aged ≥2 years, carrying at least 1 or 2 loss-of-function alleles of CYP2C19 was a risk factor for HTPR (OR=4.69, 10.00, 95%CI 1.11-19.83, 0.84-119.32, P=0.033, 0.046, respectively), and PON1 192R homozygosity and carrying at least one PON1 192R allele were protective factors against HTPR (OR=0.08, 0.13, 95%CI 0.01-0.86, 0.01-1.19, P=0.019, 0.043, respectively). Conclusion: KD children aged ≥2 years carrying CYP2C19 loss-of-function alleles and PON1 192Q are more likely to develop HTPR.

Automation of etch pit analyses on solid-state nuclear track detectors with machine learning for laser-driven ion acceleration.

Solid-state nuclear track detectors (SSNTDs) are often used as ion detectors in laser-driven ion acceleration experiments and are considered to be the most reliable ion diagnostics since they are sensitive only to ions and measure ions one by one. However, ion pit analyses require tremendous time and effort in chemical etching, microscope scanning, and ion pit identification by eyes. From a laser-driven ion acceleration experiment, there are typically millions of microscopic images, and it is practically impossible to analyze all of them by hand. This research aims to improve the efficiency and automation of SSNTD analyses for laser-driven ion acceleration. We use two sets of data obtained from calibration experiments with a conventional accelerator where ions with known nuclides and energies are generated and from actual laser experiments using SSNTDs. After chemical etching and scanning the SSNTDs with an optical microscope, we use machine learning to distinguish the ion etch pits from noises. From the results of the calibration experiment, we confirm highly accurate etch-pit detection with machine learning. We are also able to detect etch pits with machine learning from the laser-driven ion acceleration experiment, which is much noisier than calibration experiments. By using machine learning, we successfully identify ion etch pits ∼105 from more than 10 000 microscopic images with a precision of ≳95%. A million microscopic images can be examined with a recent entry-level computer within a day with high precision. Machine learning tremendously reduces the time consumption on ion etch pit analyses detected on SSNTDs.

Smoking cessation in dental setting: a narrative review on dental professionals' attitude, preparedness, practices and barriers.

Integration of smoking cessation program into routine oral health care has been advocated by World Health Organization since it brings extensive benefits to oral health. By tobacco cessation, patients are less prone to progression of periodontal disease, have less future tooth loss, have reduced risks of oral mucosal lesions and head and neck cancers. Evidence indicates that dentists are in a favorable position to deliver effective smoking cessation advice to improve patients' oral health. This article aims to present the current situation of smoking cessation in dental setting, including dental management of smoking patients, perceptions of dentists and dental students towards smoking cessation, challenges dental professionals face when carrying out cessation interventions. Patients' perspectives are also evaluated to provide a clearer picture of smoking cessation practice in the dental field. Review of past surveys show most patients welcome smoking cessation advice from dental practitioners. Meanwhile dentists may have wrong assumption that patients would disapprove them if they advise patient to quit smoking. On top of that, main obstacles identified are lack of training, inadequate treatment time and insufficient knowledge towards smoking cessation guidelines and referral routes. With regard to the potential barriers, evidence demonstrates that more trainings on smoking cessation strategies are needed. Future research in this aspect is also indicated to further foster the practice of smoking cessation counselling in dental setting.

A pilot study to determine the optimal dose of scAAVIL-1ra in a large animal model of post-traumatic osteoarthritis.

Gene therapy approaches using adeno-associated viral vectors have been successfully tested in the equine post-traumatic osteoarthritis (PTOA) model. Owing to differences in the levels of transgene expression and adverse tissue reactions observed in published studies, we sought to identify a safe therapeutic dose of scAAVIL-1ra in an inflamed and injured joint that would result in improved functional outcomes without any adverse events. scAAVIL-1ra was delivered intra-articularly over a 100-fold range, and horses were evaluated throughout and at the end of the 10-week study. A dose-related increase in IL-1ra levels with a decrease in PGE2 levels was observed, with the peak IL-1ra concentration being observed 7 days post-treatment in all groups. Perivascular infiltration with mononuclear cells was observed within the synovial membrane of the joint treated with the highest viral dose of 5 × 1012 vg, but this was absent in the lower-dosed joints. The second-highest dose of scAAVeqIL-1ra 5 × 1011 vg demonstrated elevated IL-1ra levels without any cellular response in the synovium. Taken together, the data suggest that the 10-fold lower dose of 5 × 1011vg scAAVIL-1ra would be a safe therapeutic dose in an equine model of PTOA.

Perspectives on long-acting formulations of pre-exposure prophylaxis (PrEP) among men who have sex with men who are non-adherent to daily oral PrEP in the United States.

INTRODUCTION: Pre-exposure prophylaxis (PrEP) persistence among men who have sex with men (MSM) in real world clinical settings for HIV prevention is suboptimal. New longer-acting formulations of PrEP are becoming available, including injectables, subdermal implants, and other oral medications. These longer-acting formulations have the potential to improve retention among those who have challenges remaining adherent to daily oral PrEP. METHODS: We interviewed 49 MSM who had initiated but discontinued oral PrEP at three diverse clinics across the United States. We examined participants' perspectives about long-acting PrEP formulations and how long-acting options could affect PrEP use using thematic analysis. RESULTS: Participants were not very knowledgeable about long-acting formulations of PrEP but were open to learning about them and considering use. Participants were concerned about safety and efficacy of products given that they were still newer and/or in development. Finally, participants had clear preferences for oral pills, injectables, and then subdermal implants and were most interested in options that reduced the number of visits to the clinic. CONCLUSION: Long-acting formulations of PrEP are acceptable to MSM with suboptimal PrEP persistence and have the potential to improve PrEP persistence. However, many felt they needed more information on safety, efficacy, and use to consider these options. As these long-acting formulations are implemented, public health campaigns and clinical interventions to encourage may maximize uptake particularly among those who are not currently adherent to daily oral PrEP.

The gender gap in the ownership of promising land.

Using millions of observations compiled from the public administrative data of Taiwan, we find a surprising gender inequity in terms of real estate: Men own more land than women, and the annual rate of return (ROR) of men's land outperform women's by almost 1% per year. The latter finding of gender-based ROR difference is in sharp contrast to prior evidence that women outperform men in security investment, and also suggests a quantity-and-quality double jeopardy in female land ownership which, given the heavy weight of real estate in individual wealth, has important implications for wealth inequality among men and women. Our statistical analyses suggest that such a gender-based difference in land ROR cannot be attributed to individual-level factors such as liquidity preferences, risk attitudes, investment experience, and behavioral biases, as described in the literature. Rather, we hypothesize parental gender bias-a phenomenon that is still prevalent today-to be the key macrolevel factor. To test our hypothesis, we partition our observations into two groups: an experimental group in which parents can exercise gender discretion, and a control group in which parents cannot exercise such discretion. Our empirical evidence shows that the gender difference with respect to land ROR only exists in the experimental group. For many societies with long-lasting patriarchal traditions, our analysis provides a perspective to help explain gender differences in wealth distribution and social mobility.

Spike height improves prediction of future seizure risk.

OBJECTIVE: We evaluated whether interictal epileptiform discharge (IED) rate and morphological characteristics predict seizure risk. METHODS: We evaluated 10 features from automatically detectable IEDs in a stereotyped population with self-limited epilepsy with centrotemporal spikes (SeLECTS). We tested whether the average value or the most extreme values from each feature predicted future seizure risk in cross-sectional and longitudinal models. RESULTS: 10,748 individual centrotemporal IEDs were analyzed from 59 subjects at 81 timepoints. In cross-sectional models, increases in average spike height, spike duration, slow wave rising slope, slow wave falling slope, and the most extreme values of slow wave rising slope each improved prediction of an increased risk of a future seizure compared to a model with age alone (p < 0.05, each). In longitudinal model, spike rising height improved prediction of future seizure risk compared to a model with age alone (p = 0.04) CONCLUSIONS: Spike height improves prediction of future seizure risk in SeLECTS. Several other morphological features may also improve prediction and should be explored in larger studies. SIGNIFICANCE: Discovery of a relationship between novel IED features and seizure risk may improve clinical prognostication, visual and automated IED detection strategies, and provide insights into the underlying neuronal mechanisms that contribute to IED pathology.

Post-acute phase and sequelae management of epidermal necrolysis: an international, multidisciplinary DELPHI-based consensus.

BACKGROUND: Long-term sequelae are frequent and often disabling after epidermal necrolysis (Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)). However, consensus on the modalities of management of these sequelae is lacking. OBJECTIVES: We conducted an international multicentric DELPHI exercise to establish a multidisciplinary expert consensus to standardize recommendations regarding management of SJS/TEN sequelae. METHODS: Participants were sent a survey via the online tool "Survey Monkey" consisting of 54 statements organized into 8 topics: general recommendations, professionals involved, skin, oral mucosa and teeth, eyes, genital area, mental health, and allergy workup. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). Results were analyzed according to the RAND/UCLA Appropriateness Method. RESULTS: Fifty-two healthcare professionals participated. After the first round, a consensus was obtained for 100% of 54 initially proposed statements (disagreement index < 1). Among them, 50 statements were agreed upon as 'appropriate'; four statements were considered 'uncertain', and ultimately finally discarded. CONCLUSIONS: Our DELPHI-based expert consensus should help guide physicians in conducting a prolonged multidisciplinary follow-up of sequelae in SJS-TEN.

Theory-based behavioral change interventions to improve periodontal health.

Periodontal disease is a significant global health burden affecting half of the world's population. Given that plaque and inflammation control are essential to the attainment of periodontal health, recent trends in preventive dentistry have focused on the use of behavioral models to understand patient psychology and promote self-care and treatment compliance. In addition to their uses in classifying, explaining and predicting oral hygiene practices, behavioral models have been adopted in the design of oral hygiene interventions from individual to population levels. Despite the growing focus on behavioral modification in dentistry, the currently available evidence in the field of periodontology is scarce, and interventions have primarily measured changes in patient beliefs or performance in oral hygiene behaviors. Few studies have measured their impact on clinical outcomes, such as plaque levels, gingival bleeding and periodontal pocket reduction, which serve as indicators of the patient's disease status and quality of oral self-care. The present narrative review aims to summarize selected literature on the use of behavioral models to improve periodontal outcomes. A search was performed on existing behavioral models used to guide dental interventions to identify their use in interventions measuring periodontal parameters. The main models were identified and subsequently grouped by their underlying theoretical area of focus: patient beliefs (health belief model and cognitive behavioral principles); stages of readiness to change (precaution adoption process model and transtheoretical model); planning behavioral change (health action process approach model, theory of planned behavior and client self-care commitment model); and self-monitoring (self-regulation theory). Key constructs of each model and the findings of associated interventions were described. The COM-B model, a newer behavioral change system that has been increasingly used to guide interventions and policy changes, is discussed with reference to its use in oral health settings. Within the limitations of the available evidence, interventions addressing patient beliefs, motivation, intention and self-regulation could lead to improved outcomes in periodontal health. Direct comparisons between interventions could not be made due to differences in protocol design, research populations and follow-up periods. The conclusions of this review assist clinicians with implementing psychological interventions for oral hygiene promotion and highlight the need for additional studies on the clinical effects of behavioral model-based interventions.

Gapless tuning of quantum cascade laser frequency combs with external cavity optical feedback.

We present the operation of quantum cascade laser frequency combs in an external cavity configuration. Experimental observations show dependence of comb repetition rate and optical spectrum on the external cavity length. The low phase-noise comb regime is extended to a broader range of bias currents, enabling gapless frequency tuning of the comb modes. Dual-comb measurements also confirm improved comb stability in the presence of unwanted optical feedback when operating in an external cavity configuration. These observations indicate that aside from the continuing efforts to assure low and uniform dispersion characteristics of quantum cascade laser frequency combs, the proposed simple approach of adding a broadband external cavity can significantly enhance operation of sub-optimal devices for spectroscopic applications.

Reproduction and production in a social context: Group size, reproductive skew and increasing returns.

Evolutionary success requires both production (acquisition of food, protection and warmth) and reproduction. We suggest that both may increase disproportionately as group size grows, reflecting 'increasing returns' or 'group augmentation benefits', raising fitness in groups that cooperate in production and limit reproduction to one or a few high fertility females supported by non-reproductives, with high reproductive skew. In our optimisation theory both Allee effects (when individual fitness increases with group size or density) and reproductive skew arise when increasing returns determine optimal group size and proportion of reproductive females. Depending on which of food or maternal time is more important for reproduction, evolutionary trajectories of lineages may (1) reach a boundary constraint where only one female reproduces in a period (as with African wild dogs) or (2) reach a boundary where all females reproduce during their lifetimes but only during an early life stage (human menopause) or a late life stage (birds with non-dispersing helpers), where stage length optimises the proportion of females that is reproductive at any time or (3) reach the intersection of these boundary constraints where a single reproductive female is fully specialised in reproduction (as with eusocial insects). We end with some testable hypotheses.

Local spectroscopic evidence for a nodeless magnetic kagome superconductor CeRu2.

We report muon spin rotation (µSR) experiments on the microscopic properties of superconductivity and magnetism in the kagome superconductor CeRu2withTc≃5 K. From the measurements of the temperature-dependent magnetic penetration depthλ, the superconducting order parameter exhibits nodeless pairing, which fits best to an anisotropics-wave gap symmetry. We further show that theTc/λ-2ratio is comparable to that of unconventional superconductors. Furthermore, the powerful combination of zero-field (ZF)-µSR and high-fieldµSR has been used to uncover magnetic responses across three characteristic temperatures, identified asT1∗≃110 K,T2∗≃65 K, andT3∗≃40 K. Our experiments classify CeRu2as an exceedingly rare nodeless magnetic kagome superconductor.

Facilitators for retaining men who have sex with men in pre-exposure prophylaxis care in real world clinic settings within the United States.

BACKGROUND: Pre-exposure prophylaxis (PrEP) can significantly reduce HIV acquisition especially among communities with high HIV prevalence, including men who have sex with men (MSM). Much research has been finding suboptimal PrEP persistence; however, few studies examine factors that enhance PrEP persistence in real-world settings. METHODS: We interviewed 33 patients who identified as MSM at three different PrEP clinics in three regions of the U.S. (Northeast, South, Midwest). Participants were eligible if they took PrEP and had been retained in care for a minimum of 6 months. Interviews explored social, structural, clinic-level and behavioral factors that influencing PrEP persistence. RESULTS: Through thematic analysis we identified the following factors as promoting PrEP persistence: (1) navigation to reduce out-of-pocket costs of PrEP (structural), (2) social norms that support PrEP use (social), (3) access to LGBTQ + affirming medical providers (clinical), (4) medication as part of a daily routine (behavioral), and (5) facilitation of sexual health agency (belief). DISCUSSION: In this sample, persistence in PrEP care was associated with structural and social supports as well as a high level of perceived internal control over protecting their health by taking PrEP. Patients might benefit from increased access, LGBTQ + affirming medical providers, and communications that emphasize PrEP can promote sexual health.

Label-Free Autofluorescence-Detected Mid-Infrared Photothermal Microscopy of Pharmaceutical Materials.

Label-free autofluorescence-detected photothermal mid-IR (AF-PTIR) microscopy is demonstrated experimentally and applied to test the distribution of active pharmaceutical ingredients (APIs) in a mixture containing representative pharmaceutical excipients. Two-photon excited UV-fluorescence (TPE-UVF) supports autofluorescence of native aromatic moieties using visible-light optics. Thermal modulation of the fluorescence quantum yield serves to report on infrared absorption, enabling infrared spectroscopy in the fingerprint region with a spatial resolution dictated by fluorescence. AF-PTIR provides high selectivity and sensitivity in image contrast for aromatic APIs, complementing broadly applicable optical photothermal IR (O-PTIR) microscopy based on photothermal modulation of refractive index/scattering. Mapping the API distribution is critical in designing processes for powdered dosage form manufacturing, with high spatial variance potentially producing variability in both delivered dosage and product efficacy. The ubiquity of aromatic moieties within API candidates suggests the viability of AF-PTIR in combination with O-PTIR to improve the confidence of chemical classification in spatially heterogeneous dosage forms.

Use of reactive soft tissue for primary wound closure during immediate implant placement: a two-year retrospective study.

Sockets with both hard and soft tissue defects present a challenge for immediate implant placement. A modified technique harnessing the reactive soft tissue in the extraction socket for primary closure has been reported to contribute to hard and soft tissue augmentation after immediate implantation. The aim of this study was to evaluate the effects of this novel technique on the hard and soft tissues of sockets with both buccal bone and soft tissue defects (group B) and to compare the outcomes with those obtained for sockets with intact soft tissue but buccal bone dehiscence (group A). Thirty-two implants placed in the posterior region were included: 17 in group A, 15 in group B. The implants were inserted immediately utilizing reactive soft tissue from the socket for primary closure in both groups. The changes in buccal bone dimensions after 6 months were generally comparable between the two groups. A keratinized mucosa reduction of 0.56 mm in group A and keratinized mucosa gain of 0.67 mm in group B were observed at 6 months (P = 0.009). The bone and soft tissue levels were well maintained in both groups after 2 years. This technique may be a potential treatment method for tissue augmentation during immediate implantation in posterior sockets, even when a buccal bony defect and mucogingival recession need to be repaired at the same time.

Efficacy of Kanglaite against radiotherapy-induced mucositis in head and neck cancer, a phase II trial.

PURPOSE: To explore the potential protective effect of Kanglaite injection against radiotherapy-induced mucositis in patients with head and neck cancer. PATIENTS AND METHODS: This was an open-label, single-arm, and phase II trial. The primary endpoint was the incidence of grade 3-4 radiation-induced mucositis. The secondary endpoints were hematological toxicity, non-hematological toxicity, nutritional status, and quality of life. All patients received 20g Kanglaite daily concurrently with radiotherapy. RESULTS: The data of 46 patients were available for analysis. The incidence rates of grade 3 mucositis, pain, dysphagia, and neutropenia were 10.9%, 2.2%, 10.9%, and 6.5%, respectively, while the incidence of grade 4 acute toxicities was zero. The rate of opioid use was 2.2%. Radiotherapy dose reduction was 2.2% and no irradiation field was modified. The nutritional supports were oro-enteral nutritional supplements (13.0%), TPN (10.9%), and feeding tubes (0%) during radiotherapy. After radiotherapy, 52.2% of patients lost weight, and the weight loss was <10%. The mean pain score in the QLQ-H&N35 and QLQ-C30 was <50. Patients had nearly normal physical, emotional, and cognitive functions. CONCLUSIONS: A low incidence of grade 3-4 radiation-induced mucositis and no severe acute toxic events, with favorable nutritional status and quality of life, were observed in cancer patients after Kanglaite injection. Our findings highlight the need for a prospective, multicenter, and randomized study to investigate the effect of Kanglaite injection on the reduction of radiation-induced mucositis in patients with head and neck cancer.