Nonparametric estimation of linear personalized diagnostics rules via efficient grid algorithm.

Many diseases are heterogeneous, comprised of multiple disease subgroups. It is of great interest but highly unlikely to find a single biomarker that can accurately detect such heterogeneous diseases across different subgroups. In this article, we propose to estimate a personalized diagnostic rule (PDR) to tailor more effective biomarkers to each individual according to a linear combination of his or her profiles. A standard grid search algorithm can be used to estimate the optimal linear PDR that maximizes the area under the receiver operating characteristics curve (AUC) among all the linear PDRs, but it is time-consuming especially when the number of variables is large. Alternatively, we developed an efficient grid rotation algorithm that provides a nearly suboptimal solution and studied its variation to find the optimal solution. We implemented the cross-validated forward variable selection method to find a subset of useful variables while avoid overfitting. Extensive simulations show that our proposed method reduces bias and variance. Analysis of a gastric cancer biomarker study and censored survival outcome data illustrates the practical utility of our proposed method. The proposed method is implemented in the open-source R package persDx.

Shape restricted additive hazards models: Monotone, unimodal, and U-shape hazard functions.

We consider estimation of the semiparametric additive hazards model with an unspecified baseline hazard function where the effect of a continuous covariate has a specific shape but otherwise unspecified. Such estimation is particularly useful for a unimodal hazard function, where the hazard is monotone increasing and monotone decreasing with an unknown mode. A popular approach of the proportional hazards model is limited in such setting due to the complicated structure of the partial likelihood. Our model defines a quadratic loss function, and its simple structure allows a global Hessian matrix that does not involve parameters. Thus, once the global Hessian matrix is computed, a standard quadratic programming method can be applicable by profiling all possible locations of the mode. However, the quadratic programming method may be inefficient to handle a large global Hessian matrix in the profiling algorithm due to a large dimensionality, where the dimension of the global Hessian matrix and number of hypothetical modes are the same order as the sample size. We propose the quadratic pool adjacent violators algorithm to reduce computational costs. The proposed algorithm is extended to the model with a time-dependent covariate with monotone or U-shape hazard function. In simulation studies, our proposed method improves computational speed compared to the quadratic programming method, with bias and mean square error reductions. We analyze data from a recent cardiovascular study.

Tracking the Stability of Clinically Relevant Blood Plasma Proteins with Delta-S-Cys-Albumin-A Dilute-and-Shoot LC/MS-Based Marker of Specimen Exposure to Thawed Conditions.

Biomolecular integrity can be compromised when blood plasma/serum (P/S) specimens are improperly handled. Compromised analytes can subsequently produce erroneous results-without any indication of having done so. We recently introduced an LC/MS-based marker of P/S exposure to thawed conditions called ΔS-Cys-Albumin which, aided by an established rate law, quantitatively tracks exposure of P/S to temperatures greater than their freezing point of -30 °C. The purposes of this study were to (1) evaluate ΔS-Cys-Albumin baseline values in gastrointestinal cancer patients and cancer-free control donors, (2) empirically assess the kinetic profiles of ΔS-Cys-Albumin at 23 °C, 4 °C, and -20 °C, and (3) empirically link ΔS-Cys-Albumin to the stability of clinically relevant proteins. ΔS-Cys-Albumin was measured at ≥ 9 different time points per exposure temperature in serum and K2EDTA plasma samples from 24 separate donors in aliquots kept separately at 23 °C, 4 °C, and -20 °C. Twenty-one clinically relevant plasma proteins were measured at four time points per temperature via a multiplexed immunoassay on the Luminex platform. Protein stability was assessed by mixed effects models. Coordinated shifts in stability between ΔS-Cys-Albumin and the unstable proteins were documented by repeated measures and Pearson correlations. Plasma ΔS-Cys-Albumin dropped from approximately 20% to under 5% within 96 h at 23 °C, 28 days at 4 °C, and 65 days at -20 °C. On average, 22% of the 21 proteins significantly changed in apparent concentration at each exposure temperature (p < 0.0008 with >10% shift). A linear inverse relationship was found between the percentage of proteins destabilized and ΔS-Cys-Albumin (r = -0.61; p < 0.0001)-regardless of the specific time/temperature of exposure. ΔS-Cys-Albumin tracks cumulative thawed-state exposure. These results now enable ΔS-Cys-Albumin to approximate the percentage of clinically relevant proteins that have been compromised by incidental plasma exposure to thawed-state conditions.

Development of a rapid lateral flow assay for detection of anti-coccidioidal antibodies.

Coccidioides spp. are dimorphic fungi that are capable of infecting human and non-human mammals and can cause diverse manifestations of coccidioidomycosis or Valley fever (VF). In combination with clinical symptoms and radiographic findings, antibody-based diagnostic tests are often used to diagnose and monitor patients with VF. Chitinase 1 (CTS1) has previously been identified as the seroreactive antigen used in these diagnostic assays to detect anticoccidial IgG. Here, an indirect enzyme-linked immunosorbent assay to detect IgG to CTS1 demonstrated 165 of 178 (92.7%) patients with a positive result by immunodiffusion (ID) and/or complement fixation (CF) had antibodies to the single antigen CTS1. We then developed a rapid antibody lateral flow assay (LFA) to detect anti-CTS1 antibodies. Out of 143 samples tested, the LFA showed 92.9% positive percent agreement [95% confidence interval (CI), 84.3%-96.9%] and 97.7% negative percent agreement (95% CI, 87.9%-99.6%) with ID and CF assays. Serum or plasma from canines, macaques, and dolphins was also tested by the CTS1 LFA. Test line densities of the CTS1 LFA correlated in a linear manner with the reported CF and ID titers for human and non-human samples, respectively. This 10-min point-of-care test for the rapid detection of anti-coccidioidal antibodies could help to inform healthcare providers in real-time, potentially improving the efficiency of healthcare delivery.

Helicobacter pylori Immunoproteomic Profiles in Gastric Cancer.

Chronic Helicobacter pylori infection is the major risk factor for gastric cancer (GC). However, only some infected individuals develop this neoplasia. Previous H. pylori serology studies have been limited by investigating small numbers of candidate antigens. Therefore, we evaluated humoral responses to a nearly complete H. pylori immunoproteome (1527 proteins) among 50 GC cases and 50 controls using Nucleic Acid Programmable Protein Array (NAPPA). Seropositivity was defined as median normalized intensity ≥2 on NAPPA, and 53 anti-H. pylori antibodies had >10% seroprevalence. Anti-GroEL exhibited the greatest seroprevalence (77% overall), which agreed well with ELISA using whole-cell lysates of H. pylori cells. After an initial screen by H. pylori-NAPPA, we discovered and verified that 12 antibodies by ELISA in controls had ≥15% of samples with an optical reading value exceeding the 95th percentile of the GC group. ELISA-verified antibodies were validated blindly in an independent set of 100 case-control pairs. As expected, anti-CagA seropositivity was positively associated with GC (odds ratio, OR = 5.5; p < 0.05). After validation, six anti-H. pylori antibodies showed lower seropositivity in GC, with ORs ranging from 0.44 to 0.12 (p < 0.05): anti-HP1118/Ggt, anti-HP0516/HsIU, anti-HP0243/NapA, anti-HP1293/RpoA, anti-HP0371/FabE, and anti-HP0875/KatA. Among all combinations, a model with anti-Ggt, anti-HslU, anti-NapA, and anti-CagA had an area under the curve of 0.73 for discriminating GC vs. controls. This study represents the first comprehensive assessment of anti-H. pylori humoral profiles in GC. Decreased responses to multiple proteins in GC may reflect mucosal damage and decreased bacterial burden. The higher prevalence of specific anti-H. pylori antibodies in controls may suggest immune protection against GC development.

Identification of anti-Epstein-Barr virus (EBV) antibody signature in EBV-associated gastric carcinoma.

BACKGROUND: Around 10% of gastric carcinomas (GC) contain Epstein-Barr virus (EBV) DNA. We characterized the GC-specific antibody response to this common infection, which may provide a noninvasive method to detect EBV-positive GC and elucidate its contribution to carcinogenesis. METHODS: Plasma samples from EBV-positive (n = 28) and EBV-negative (n = 34) Latvian GC patients were immune-profiled against 85 EBV proteins on a multi-microbial Nucleic Acid Programmable Protein Array (EBV-NAPPA). Antibody responses were normalized for each sample as ratios to the median signal intensity (MNI) across all antigens, with seropositivity defined as MNI ≥ 2. Antibodies with ≥ 20% sensitivity at 95% specificity for tumor EBV status were verified by enzyme-linked immunosorbent assay (ELISA) and validated in independent samples from Korea and Poland (n = 24 EBV-positive, n = 65 EBV-negative). RESULTS: Forty anti-EBV IgG and eight IgA antibodies were detected by EBV-NAPPA in ≥ 10% of EBV-positive or EBV-negative GC patients, of which nine IgG antibodies were discriminative for tumor EBV status. Eight of these nine were verified and seven were validated by ELISA: anti-LF2 (odds ratio = 110.0), anti-BORF2 (54.2), anti-BALF2 (44.1), anti-BaRF1 (26.7), anti-BXLF1 (12.8), anti-BRLF1 (8.3), and anti-BLLF3 (5.4). The top three had areas under receiver operating characteristics curves of 0.81-0.85 for distinguishing tumor EBV status. CONCLUSIONS: The EBV-associated GC-specific humoral response was exclusively directed against lytic cycle immediate-early and early antigens, unlike other EBV-associated malignancies such as nasopharyngeal carcinoma and lymphoma where humoral response is primarily directed against late lytic antigens. Specific anti-EBV antibodies could have utility for clinical diagnosis, epidemiologic studies, and immune-based precision treatment of EBV-positive GC.

Identifying App-Based Meditation Habits and the Associated Mental Health Benefits: Longitudinal Observational Study.

BACKGROUND: Behavioral habits are often initiated by contextual cues that occur at approximately the same time each day; so, it may be possible to identify a reflexive habit based on the temporal similarity of repeated daily behavior. Mobile health tools provide the detailed, longitudinal data necessary for constructing such an indicator of reflexive habits, which can improve our understanding of habit formation and help design more effective mobile health interventions for promoting healthier habits. OBJECTIVE: This study aims to use behavioral data from a commercial mindfulness meditation mobile phone app to construct an indicator of reflexive meditation habits based on temporal similarity and estimate the association between temporal similarity and meditation app users' perceived health benefits. METHODS: App-use data from June 2019 to June 2020 were analyzed for 2771 paying subscribers of a meditation mobile phone app, of whom 86.06% (2359/2771) were female, 72.61% (2012/2771) were college educated, 86.29% (2391/2771) were White, and 60.71% (1664/2771) were employed full-time. Participants volunteered to complete a survey assessing their perceived changes in physical and mental health from using the app. Receiver operating characteristic curve analysis was used to evaluate the ability of the temporal similarity measure to predict future behavior, and variable importance statistics from random forest models were used to corroborate these findings. Logistic regression was used to estimate the association between temporal similarity and self-reported physical and mental health benefits. RESULTS: The temporal similarity of users' daily app use before completing the survey, as measured by the dynamic time warping (DTW) distance between app use on consecutive days, significantly predicted app use at 28 days and at 6 months after the survey, even after controlling for users' demographic and socioeconomic characteristics, total app sessions, duration of app use, and number of days with any app use. In addition, the temporal similarity measure significantly increased in the area under the receiver operating characteristic curve (AUC) for models predicting any future app use in 28 days (AUC=0.868 with DTW and 0.850 without DTW; P<.001) and for models predicting any app use in 6 months (AUC=0.821 with DTW and 0.802 without DTW; P<.001). Finally, a 1% increase in the temporal similarity of users' daily meditation practice with the app over 6 weeks before the survey was associated with increased odds of reporting mental health improvements, with an odds ratio of 2.94 (95% CI 1.832-6.369). CONCLUSIONS: The temporal similarity of the meditation app use was a significant predictor of future behavior, which suggests that this measure can identify reflexive meditation habits. In addition, temporal similarity was associated with greater perceived mental health benefits, which demonstrates that additional mental health benefits may be derived from forming reflexive meditation habits.

Evaluation of a Test Dose Strategy for Pharmacokinetically-Guided Busulfan Dosing for Hematopoietic Stem Cell Transplantation.

Targeted busulfan dosing helps limit chemotherapy-related toxicity and optimize disease outcomes in hematopoietic stem cell transplantation (HCT). The objective of this study was to evaluate busulfan exposure from a pharmacokinetic (PK)-guided dosing strategy using a test dose. This retrospective evaluation included adult patients who underwent HCT at our institution with busulfan-based myeloablative (>9 mg/kg) conditioning between January 2014 and October 2015. A weight-based test dose of 0.8 mg/kg was used with PK assessments to predict area under the curve (AUCpred) achieved with weight-based dosing, with a target AUC of 4800 µM*minute (AUCtarget). PK from the test dose was then used to calculate a PK-guided first myeloablative busulfan dose. PK assessments were also done after the first dose to assess if the goal area under the curve (AUC) had been achieved (AUCfirst). A PK-guided first dose resulted in achievement of target AUC with target ranges of ±10% in 50% of patients, ±15% in 75%, and ±20% in 94%. This was an improved rate of target achievement compared with the 33%, 44%, and 63% of patients who achieved the desired AUC for these respective target ranges when using weight-based dosing (P = .12, .004, and <.001, respectively). The PK-guided strategy also decreased the variability of AUC from 3.6-fold in AUCpred from the weight-based test doses (2700.8 to 9631 µM*minute; SD, 1211.6 µM*minute) to 1.8-fold in AUCfirst from the PK-guided first doses (3672.1 to 6609.8 µM*minute; SD, 574.7 µM*minute). This reflects a 2-fold improvement in AUC variability with a PK-guided dosing strategy. This is also improved from the 3-fold variability in AUC reported in other studies. Weight and body surface area were significantly associated with the likelihood of AUCfirst being within the ±10% target range (P = .04 for both associations). There was no significant association between AUCfirst and death, relapse, or a composite of the two. These results demonstrate a significant improvement in target AUC attainment and less interpatient variability with PK-guided dosing using a test dose strategy compared with weight-based dosing.

Three-year clinical evaluation of universal adhesives in non-carious cervical lesions.

PURPOSE: To compare the performance of universal adhesives containing different monomers, namely 10-methacryloyloxydecyl dihydrogen phosphate (10-MDP) and dipentaerythritol penta-acrylate monophosphate (PENTA), in the restoration of non-carious cervical lesions (NCCLs). METHODS: This was a randomized controlled clinical trial involving 63 subjects in need of restorations of 203 NCCLs. Notch-shaped lesions were restored with Kalore (GC Corporation) after application of Scotchbond Universal (SU) or Prime&Bond Elect (PBE) following the etch-and-rinse (ER) or self-etch (SE) technique. Restorations were assessed after 1 week, 18 and 36 months. Logistic regression was performed for each outcome separately with compound symmetric variance-covariance structure assumed to consider a correlation of restorations within subjects. All analyses were conducted using SAS 9.4 (SAS). RESULTS: 150 teeth in 41 subjects were assessed at 36 months. Three restorations in the PBE_SE group failed the retention criterium. Statistically significant differences were reached for the following comparisons: restorations with SU_SE were 75% less likely to maintain a score of Alfa for marginal discoloration than PBE_SE; restorations with PBE_SE were 83% less likely to maintain a score of Alfa for marginal adaptation than PBE_ER. CLINICAL SIGNIFICANCE: More than 20% of restorations restored with universal adhesives developed marginal degradation after 36 months. The impact of phosphoric acid on the restoration seems to be material-dependent.

Complementary and alternative medicine use among children with mental health issues: results from the National Health Interview Survey.

BACKGROUND: Mental health issues in children have become a serious public health concern in the U.S. within the past few decades. Emerging evidence suggests that Complementary and Alternative Medicine (CAM) can be beneficial for various mental health issues. However, little is known about the prevalence, reasons, and associated factors of CAM use among this population in the U.S. The purpose of this study is to examine the characteristics of CAM use among U.S. children with mental health issues. METHODS: Utilizing the 2012 National Health Interview Survey data, we used descriptive analysis, Wald F-statistics, and multivariable survey logistic regression models to examine the prevalence, patterns, and associated factors of CAM use in children aged 4-17 (n = 10,233) adjusting for the complex sampling design. RESULTS: CAM use is more popular among children with mental health issues compared with those without (19.2% vs. 10.1%, p < 0.001). Herbal remedies (9.1%), mind-body therapies (5.5%), and chiropractic care (5.3%) were the most frequently used modalities. Primary reasons for children to use CAM are because they are helpful (69.2%), natural (55.9%), and holistic (44.7%). The majority of CAM users perceived CAM therapies are helpful. Predictors of CAM use are children who are female, whose parents had a higher educational level and socioeconomic status, and who had at least one co-morbid medical condition. Only 18.4% of CAM usage was recommended by medical doctors. CONCLUSIONS: Approximately 10 million parents of children with mental health issues reported the use of CAM therapies, mainly because of their desire for a more natural and holistic healthcare approach. Given that the majority of CAM users perceived CAM therapies as helpful, future studies should investigate the unique contributions of CAM in pediatric psychiatric care. Because a low percentage of CAM use was recommended by medical doctors, educational interventions designed to equip medical professionals with CAM knowledge and experience will be conducive to improving effective patient-physician communication in clinical settings. Since CAM use is reported as more prevalent by parents' of children with higher education and family income, effective strategies designed to reduce disparities in accessing promising CAM therapies are warranted.

Patients with primary membranous nephropathy are at high risk of cardiovascular events.

Here we conducted a retrospective study to examine the risk of cardiovascular events (CVEs) relative to that of end-stage renal disease (ESRD) in patients with primary membranous nephropathy, in a discovery cohort of 404 patients. The cumulative incidence of CVEs was estimated in the setting of the competing risk of ESRD with risk factors for CVEs assessed by multivariable survival analysis. The observed cumulative incidences of CVEs were 4.4%, 5.4%, 8.2%, and 8.8% at 1, 2, 3, and 5 years respectively in the primary membranous nephropathy cohort. In the first 2 years after diagnosis, the risk for CVEs was similar to that of ESRD in the entire cohort, but exceeded it among patients with preserved renal function. Accounting for traditional risk factors and renal function, the severity of nephrosis at the time of the event (hazard ratio 2.1, 95% confidence interval 1.1 to 4.3) was a significant independent risk factor of CVEs. The incidence and risk factors of CVEs were affirmed in an external validation cohort of 557 patients with primary membranous nephropathy. Thus early in the course of disease, patients with primary membranous nephropathy have an increased risk of CVEs commensurate to, or exceeding that of ESRD. Hence, reduction of CVEs should be considered as a therapeutic outcome measure and focus of intervention in primary membranous nephropathy.

A Predictive Model for Root Caries Incidence.

This study aimed to find the set of risk indicators best able to predict root caries (RC) incidence in caries-active adults utilizing data from the Xylitol for Adult Caries Trial (X-ACT). Five logistic regression models were compared with respect to their predictive performance for incident RC using data from placebo-control participants with exposed root surfaces at baseline and from two study centers with ancillary data collection (n = 155). Prediction performance was assessed from baseline variables and after including ancillary variables [smoking, diet, use of removable partial dentures (RPD), toothbrush use, income, education, and dental insurance]. A sensitivity analysis added treatment to the models for both the control and treatment participants (n = 301) to predict RC for the control participants. Forty-nine percent of the control participants had incident RC. The model including the number of follow-up years at risk, the number of root surfaces at risk, RC index, gender, race, age, and smoking resulted in the best prediction performance, having the highest AUC and lowest Brier score. The sensitivity analysis supported the primary analysis and gave slightly better performance summary measures. The set of risk indicators best able to predict RC incidence included an increased number of root surfaces at risk and increased RC index at baseline, followed by white race and nonsmoking, which were strong nonsignificant predictors. Gender, age, and increased number of follow-up years at risk, while included in the model, were also not statistically significant. The inclusion of health, diet, RPD use, toothbrush use, income, education, and dental insurance variables did not improve the prediction performance.

Phase I/II Trial of Dose-Escalated Busulfan Delivered by Prolonged Continuous Infusion in Allogeneic Transplant Patients.

Intensive chemotherapy or chemotherapy plus irradiation and allogeneic stem cell transplantation can be curative for patients with hematologic diseases. Reduced-intensity transplants can also achieve cure and result in less treatment-related mortality but higher relapse rates. Thus, optimizing the conditioning regimens used in allogeneic transplantation remains an important goal. We conducted a phase I/II trial to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of a continuous infusion of busulfan over 90 hours in conjunction with fludarabine followed by allogeneic related or unrelated donor transplant. Fifty-four patients with advanced hematologic malignancies were enrolled on this study. The MTD was identified as a 24-hour area under the curve (AUC) of approximately 7095 µM/min, which represents a 43% increase over the standard total daily AUC dose of 4800 µM/min given by intermittent schedules. DLTs at doses over 8000 µM/min were identified by a desquamative skin rash and mucositis. No dose-related increase in hepatic, pulmonary, or other organ toxicities were seen, whereas efficacy appeared to be improved at higher dose levels. Continuous-infusion busulfan with intermittent fludarabine provides an alternative treatment strategy that is generally well tolerated and permits an increase in total busulfan dose with encouraging efficacy. (NCI study no. NCT00448357.).

Three-year clinical evaluation of a silorane composite resin.

STATEMENT OF PROBLEM: Composite resins are still outperformed by amalgams in the clinical practice with secondary caries and fractures being their most common failures. A material that suffers less polymerization shrinkage might improve the clinical performance of composite resins. PURPOSE: To evaluate the clinical performance of a low-shrink silorane-based composite resin (Filtek LS Low Shrink Posterior Restorative, 3M ESPE, St. Paul, MN, USA) in comparison with a methacrylate-based composite resin (Tetric EvoCeram, Ivoclar Vivadent, Schaan, Principality of Liechtenstein) over time. MATERIALS AND METHODS: Candidates in need of Class II composite resin restorations participated in this randomized controlled clinical trial. Those were 25 female and six male subjects with average age of 44.3 ± 12.7 years. Participants received 82 restorations, being 54 in premolars and 28 in molars. Procedures, which included the restoration of primary caries lesions or replacement of failing restorations, were done using modified preparations with no bevels or additional retention. Restorations were placed using Filtek LS (and dedicated self-etch adhesive) or Tetric EvoCeram (with AdheSE, Ivoclar Vivadent), following manufacturers' instructions. Incremental placement technique was applied and the restorations were immediately finished. Follow-up evaluations occurred at six, 12, 24, and 36 months and were done using the Fédération Dentaire Internationale criteria. Statistical analysis was performed using generalized estimating equations. RESULTS: The recall rate at 36 months was 89%. All interaction terms were not significant. CONCLUSIONS: Filtek LS performs as well as Tetric EvoCeram performs in the clinical setting at 36 months. CLINICAL SIGNIFICANCE: The silorane-based composite resin Filtek LS and the conventional methacrylate-based composite resin Tetric EvoCeram performed similarly well in posterior restorations over at least 36 months of clinical service.

Development of a Study Protocol for Evaluation of a Novel Measure to Incorporate Information Freshness into Network Analysis of Online Resources for COVID-19.

We proposed a novel measure, Degree of Connectivity with Integration of Freshness (DCIF), to incorporate information freshness into analysis of online resource networks. We conducted a pilot study to apply this new measure to a dataset of online information resources related to COVID-19 risk assessment. Among the 52 nodes, we recorded statistically significant difference between the numerical values of DCIF and the traditional structural measure Degree of Connectivity (DC). Manual reviews of 18 selected nodes showed that DCIF outperformed DC in 11 of them, suggesting potential promise of the proposed new measure. We finalized the protocol for manual review based on the pilot and started a full-scale study. The proposed new measure has the potential to provide quantitative assessment on information freshness for timely and effective dissemination of clinical evidence. Further research is required to address the limitations of this pilot study and to examine the generalization of the findings.

Quantitative assessment of multiple pathogen exposure and immune dynamics at scale.

IMPORTANCE: Serology reveals exposure to pathogens, as well as the state of autoimmune and other clinical conditions. It is used to evaluate individuals and their histories and as a public health tool to track epidemics. Employing a variety of formats, studies nearly always perform serology by testing response to only one or a few antigens. However, clinical outcomes of new infections also depend on which previous infections may have occurred. We developed a high-throughput serology method that evaluates responses to hundreds of antigens simultaneously. It can be used to evaluate thousands of samples at a time and provide a quantitative readout. This tool will enable doctors to monitor which pathogens an individual has been exposed to and how that changes in the future. Moreover, public health officials could track populations and look for infectious trends among large populations. Testing many potential antigens at a time may also aid in vaccine development.

Discovery of a Unique Set of Dog-Seroreactive Coccidioides Proteins Using Nucleic Acid Programmable Protein Array.

Valley Fever (VF), caused by fungi in the genus Coccidioides, is a prevalent disease in southwestern and western parts of the United States that affects both humans and animals, such as dogs. Although the immune responses to infection with Coccidioides spp. are not fully characterized, antibody-detection assays are used in conjunction with clinical presentation and radiologic findings to aid in the diagnosis of VF. These assays often use Complement Fixation (CF) and Tube Precipitin (TP) antigens as the main targets of IgG and IgM reactivity, respectively. Our group previously reported evidence of over 800 genes expressed at the protein level in C. posadasii. However, antibody reactivity to the majority of these proteins has never been explored. Using a new, high-throughput screening technology, the Nucleic Acid Programmable Protein Array (NAPPA), we screened serum specimens from dogs against 708 of these previously identified proteins for IgG reactivity. Serum from three separate groups of dogs was analyzed and revealed a small panel of proteins to be further characterized for immuno-reactivity. In addition to CF/CTS1 antigen, sera from most infected dogs showed antibody reactivity to endo-1,3-betaglucanase, peroxisomal matrix protein, and another novel reactive protein, CPSG_05795. These antigens may provide additional targets to aid in antibody-based diagnostics.

Effects of lip revision surgery on long-term orosensory function in patients with cleft lip/palate.

OBJECTIVE : To determine whether secondary lip revision surgery impacts sensitivity of the upper lip. DESIGN : A three-group, parallel, prospective, nonrandomized clinical trial. SETTING : University of North Carolina School of Dentistry. PATIENTS, PARTICIPANTS : Three groups: (1) patients with repaired cleft lip/palate who were scheduled for lip revision (revision; N = 20); (2) patients with repaired cleft lip/palate who did not receive a lip revision (non-revision; N = 13); and (3) non-cleft control subjects (non-cleft; N = 22). Interventions : Lip revision surgery. MAIN OUTCOME MEASURES : Measures of (1) two-point perception threshold (two-point), (2) warmth detection threshold (warm), and (3) cool detection threshold (cool) were obtained from two sites on the upper lip vermilion. The revision participants were tested approximately 1 week before surgery and then approximately 3 and 12 months after surgery. The non-revision and non-cleft participants were tested at similar times. RESULTS : There were no significant differences among the three groups at baseline for two-point, warm, or cool. The main effects of group, age, sex, and time were not statistically significant for the two-point or warm (p > .05). The mean differences between the 3- and 12-month follow-up visits and baseline for two-point and warm were small for all three groups. For cool, group was statistically significant (p = .04), the difference in the non-revision group between follow-up and baseline was 31% to 34% higher than in the non-cleft group (p = .01). CONCLUSIONS : Although at postsurgery revision participants exhibited threshold values comparable to presurgical values, the sensory differences observed among subgroups of participants with cleft lip are complex.

J-score: a robust measure of clustering accuracy.

Background: Clustering analysis discovers hidden structures in a data set by partitioning them into disjoint clusters. Robust accuracy measures that evaluate the goodness of clustering results are critical for algorithm development and model diagnosis. Common problems of clustering accuracy measures include overlooking unmatched clusters, biases towards excessive clusters, unstable baselines, and difficulties of interpretation. In this study, we presented a novel accuracy measure, J-score, to address these issues. Methods: Given a data set with known class labels, J-score quantifies how well the hypothetical clusters produced by clustering analysis recover the true classes. It starts with bidirectional set matching to identify the correspondence between true classes and hypothetical clusters based on Jaccard index. It then computes two weighted sums of Jaccard indices measuring the reconciliation from classes to clusters and vice versa. The final J-score is the harmonic mean of the two weighted sums. Results: Through simulation studies and analyses of real data sets, we evaluated the performance of J-score and compared with existing measures. Our results show that J-score is effective in distinguishing partition structures that differ only by unmatched clusters, rewarding correct inference of class numbers, addressing biases towards excessive clusters, and having a relatively stable baseline. The simplicity of its calculation makes the interpretation straightforward. It is a valuable tool complementary to other accuracy measures. We released an R/jScore package implementing the algorithm.

Mindfulness Meditation App Abandonment During the COVID-19 Pandemic: An Observational Study.

Objectives: Mindfulness meditation apps are used by millions of adults in the USA to improve mental health. However, many new app subscribers quickly abandon their use. The purpose of this study was to determine the behavioral, demographic, and socioeconomic factors associated with the abandonment of meditation apps during the COVID-19 pandemic. Method: A survey was distributed to subscribers of a popular meditation app, Calm, at the start of the COVID-19 pandemic in March 2020 that assessed meditation app behavior and meditation habit strength, as well as demographic and socioeconomic information. App usage data were also collected from the start of each participant's subscription until May 2021. A total of 3275 respondents were included in the analyses. Participants were divided into three cohorts according to their subscription start date: (1) long-term subscribers (> 1 year before pandemic start), (2) pre-pandemic subscribers (< 4 months before pandemic start), and (3) pandemic subscribers (joined during the pandemic). Results: Meditating after an existing routine was associated with a lower risk of app abandonment for pre-pandemic subscribers (hazard ratio = 0.607, 95% CI: 0.422, 0.874; p = 0.007) and for pandemic subscribers (hazard ratio = 0.434, 95% CI: 0.285, 0.66; p < 0.001). Additionally, meditating "whenever I can" was associated with lower risk of abandonment among pandemic subscribers (hazard ratio = 0.437, 95% CI: 0.271, 0.706; p < 0.001), and no behavioral factors were significant predictors of app abandonment among the long-term subscribers. Conclusions: These results show that combining meditation with an existing daily routine was a commonly utilized strategy for promoting persistent meditation app use during the COVID-19 pandemic for many subscribers. This finding supports existing evidence that pairing new behaviors with an existing routine is an effective method for establishing new health habits. Preregistration: This study is not pre-registered.