The rediscovery of a relict unlocks the first global phylogeny of whip spiders (Amblypygi).

Asymmetrical rates of cladogenesis and extinction abound in the Tree of Life, resulting in numerous minute clades that are dwarfed by larger sister groups. Such taxa are commonly regarded as phylogenetic relicts or "living fossils" when they exhibit an ancient first appearance in the fossil record and prolonged external morphological stasis, particularly in comparison to their more diversified sister groups. Due to their special status, various phylogenetic relicts tend to be well-studied and prioritized for conservation. A notable exception to this trend is found within Amblypygi ("whip spiders"), a visually striking order of functionally hexapodous arachnids that are notable for their antenniform first walking leg pair (the eponymous "whips"). Paleoamblypygi, the putative sister group to the remaining Amblypygi, is known from Late Carboniferous and Eocene deposits, but is survived by a single living species, Paracharon caecus Hansen, 1921, that was last collected in 1899. Due to the absence of genomic sequence-grade tissue for this vital taxon, there is no global molecular phylogeny for Amblypygi to date, nor a fossil-calibrated estimation of divergences within the group. Here, we report a previously unknown species of Paleoamblypygi from a cave site in Colombia. Capitalizing upon this discovery, we generated the first molecular phylogeny of Amblypygi, integrating ultraconserved element sequencing with legacy Sanger datasets and including described extant genera. To quantify the impact of sampling Paleoamblypygi on divergence time estimation, we performed in silico experiments with pruning of Paracharon. We demonstrate that the omission of relicts has a significant impact on the accuracy of node dating approaches that outweighs the impact of excluding ingroup fossils, which bears upon the ancestral range reconstruction for the group. Our results underscore the imperative for biodiversity discovery efforts in elucidating the phylogenetic relationships of "dark taxa", and especially phylogenetic relicts in tropical and subtropical habitats. The lack of reciprocal monophyly for Charontidae and Charinidae leads us to subsume them into one family, Charontidae, new synonymy.

Whole Genomes Reveal Evolutionary Relationships and Mechanisms Underlying Gene-Tree Discordance in Neodiprion Sawflies.

Rapidly evolving taxa are excellent models for understanding the mechanisms that give rise to biodiversity. However, developing an accurate historical framework for comparative analysis of such lineages remains a challenge due to ubiquitous incomplete lineage sorting and introgression. Here, we use a whole-genome alignment, multiple locus-sampling strategies, and summary-tree and SNP-based species-tree methods to infer a species tree for eastern North American Neodiprion species, a clade of pine-feeding sawflies (Order: Hymenopteran; Family: Diprionidae). We recovered a well-supported species tree that-except for three uncertain relationships-was robust to different strategies for analyzing whole-genome data. Nevertheless, underlying gene-tree discordance was high. To understand this genealogical variation, we used multiple linear regression to model site concordance factors estimated in 50-kb windows as a function of several genomic predictor variables. We found that site concordance factors tended to be higher in regions of the genome with more parsimony-informative sites, fewer singletons, less missing data, lower GC content, more genes, lower recombination rates, and lower D-statistics (less introgression). Together, these results suggest that incomplete lineage sorting, introgression, and genotyping error all shape the genomic landscape of gene-tree discordance in Neodiprion. More generally, our findings demonstrate how combining phylogenomic analysis with knowledge of local genomic features can reveal mechanisms that produce topological heterogeneity across genomes.

Landscape-scale concordance between local ecological knowledge for tropical wild species and remote sensing of land cover.

Monitoring the status of species is crucial for biodiversity conservation and sustainable resource management in tropical forests, but conventional in situ monitoring methods are impractical over large scales. Scientists have resorted to two potentially complementary approaches: local ecological knowledge (LEK) and remote sensing. To gauge the potential of combining LEK and remote sensing for assessing species status at landscape scales, a large-scale assessment of the reliability of both measures is critical but hampered by the lack of ground-level data. We conducted a landscape-scale assessment of LEK and remote sensing, using a survey of over 900 communities (a near census in our study area) and nearly 4,000 households in 235 randomly selected communities in the Peruvian Amazon-the largest LEK survey as yet undertaken in tropical forests. The survey collected LEK data on the presence of 20 indicator species from both community leaders/elders and randomly sampled households. We assessed LEK and remotely sensed land cover-forest cover and nonmain channel open water-as proxies for species habitat, across species (game, fish, and timber), over time (current and historical), and by indigeneity (Indigenous peoples and mestizos). Overall, LEK and remotely sensed land cover corroborate each other well. Concordance is highest for the current status of game species reported by sampled households, as is the concordance of historical LEK from Indigenous community leaders/elders. The results point to the promise of combining LEK and remote sensing in monitoring the status of species in data-poor tropical forests.

Patient-physician sex concordance and outcomes in cardiovascular disease: a systematic review.

The sex disparity in outcomes of patients with cardiovascular disease is well-described and has persisted across recent decades. While there have been several proposed mechanisms to explain this disparity, there are limited data on female patient-physician sex concordance and its association with outcomes. The authors review the existing literature on the relationship between patient-physician sex concordance and clinical outcomes in patients with cardiovascular disease, the evidence of a benefit in clinical outcomes with female patient-physician sex concordance, and the possible drivers of such a benefit and highlight directions for future study.

Comparative diagnostic utility of SARS-CoV-2 rapid antigen and molecular testing in a community setting.

BACKGROUND: SARS-CoV-2 antigen-detection rapid diagnostic tests (Ag-RDTs) have become widely utilized but longitudinal characterization of their community-based performance remains incompletely understood. METHODS: This prospective longitudinal study at a large public university in Seattle, WA utilized remote enrollment, online surveys, and self-collected nasal swab specimens to evaluate Ag-RDT performance against real-time reverse transcription polymerase chain reaction (rRT-PCR) in the context of SARS-CoV-2 Omicron. Ag-RDT sensitivity and specificity within 1 day of rRT-PCR were evaluated by symptom status throughout the illness episode and Orf1b cycle threshold (Ct). RESULTS: From February to December 2022, 5,757 participants reported 17,572 Ag-RDT results and completed 12,674 rRT-PCR tests, of which 995 (7.9%) were rRT-PCR-positive. Overall sensitivity and specificity were 53.0% (95% CI: 49.6-56.4%) and 98.8% (98.5-99.0%), respectively. Sensitivity was comparatively higher for Ag-RDTs used 1 day after rRT-PCR (69.0%), 4 to 7 days post-symptom onset (70.1%), and Orf1b Ct ≤20 (82.7%). Serial Ag-RDT sensitivity increased with repeat testing ≥2 (68.5%) and ≥4 (75.8%) days after an initial Ag-RDT-negative result. CONCLUSION: Ag-RDT performance varied by clinical characteristics and temporal testing patterns. Our findings support recommendations for serial testing following an initial Ag-RDT-negative result, especially among recently symptomatic persons or those at high-risk for SARS-CoV-2 infection.

Augmented interpretation of HER2, ER, and PR in breast cancer by artificial intelligence analyzer: enhancing interobserver agreement through a reader study of 201 cases.

BACKGROUND: Accurate classification of breast cancer molecular subtypes is crucial in determining treatment strategies and predicting clinical outcomes. This classification largely depends on the assessment of human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR) status. However, variability in interpretation among pathologists pose challenges to the accuracy of this classification. This study evaluates the role of artificial intelligence (AI) in enhancing the consistency of these evaluations. METHODS: AI-powered HER2 and ER/PR analyzers, consisting of cell and tissue models, were developed using 1,259 HER2, 744 ER, and 466 PR-stained immunohistochemistry (IHC) whole-slide images of breast cancer. External validation cohort comprising HER2, ER, and PR IHCs of 201 breast cancer cases were analyzed with these AI-powered analyzers. Three board-certified pathologists independently assessed these cases without AI annotation. Then, cases with differing interpretations between pathologists and the AI analyzer were revisited with AI assistance, focusing on evaluating the influence of AI assistance on the concordance among pathologists during the revised evaluation compared to the initial assessment. RESULTS: Reevaluation was required in 61 (30.3%), 42 (20.9%), and 80 (39.8%) of HER2, in 15 (7.5%), 17 (8.5%), and 11 (5.5%) of ER, and in 26 (12.9%), 24 (11.9%), and 28 (13.9%) of PR evaluations by the pathologists, respectively. Compared to initial interpretations, the assistance of AI led to a notable increase in the agreement among three pathologists on the status of HER2 (from 49.3 to 74.1%, p < 0.001), ER (from 93.0 to 96.5%, p = 0.096), and PR (from 84.6 to 91.5%, p = 0.006). This improvement was especially evident in cases of HER2 2+ and 1+, where the concordance significantly increased from 46.2 to 68.4% and from 26.5 to 70.7%, respectively. Consequently, a refinement in the classification of breast cancer molecular subtypes (from 58.2 to 78.6%, p < 0.001) was achieved with AI assistance. CONCLUSIONS: This study underscores the significant role of AI analyzers in improving pathologists' concordance in the classification of breast cancer molecular subtypes.

Histological diagnostic discrepancy and its clinical impact in bone and soft tissue tumors referred to a sarcoma center.

Histological diagnosis of sarcomas (malignant bone and soft tissue tumors) is challenging due to their rarity, morphological diversity, and constantly evolving diagnostic criteria. In this study, we aimed to assess the concordance in histological diagnosis of bone and soft tissue tumors between referring hospitals and a tertiary sarcoma center and analyzed the clinical impact of the diagnostic alteration. We analyzed 628 consecutively accessioned specimens from 624 patients who visited a specialized sarcoma center for treatment. The diagnoses at referring hospitals and those at the sarcoma center were compared and classified into four categories: agreed, disagreed, specified, and de-specified. Of the 628 specimens, the diagnoses agreed in 403 (64.2%) specimens, whereas some changes were made in 225 (35.8%) specimens: disagreed in 153 (24.3%), specified in 52 (8.3%), and de-specified in 20 (3.2%) cases. The benign/intermediate/malignant judgment changed for 92 cases (14.6%). The diagnostic change resulted in patient management modification in 91 cases (14.5%), including surgical and medical treatment changes. The main inferred reason for the diagnostic discrepancies was a different interpretation of morphological findings of the tumor, which accounted for 48.9% of the cases. This was followed by the unavailability of specialized immunohistochemical antibodies and the unavailability of genetic analysis. In summary, our study clarified the actual clinical impact of diagnostic discrepancy in bone and soft tissue tumors. This may underscore the value of pathology consultation, facilitating access to specialized diagnostic tools, and continued education. These measures are expected to improve diagnostic precision and ultimately benefit patients.

Clinical profiles and mortality rates are similar for metabolic dysfunction-associated steatotic liver disease and non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Recently, the term metabolic dysfunction-associated steatotic liver disease (MASLD) has replaced non-alcoholic fatty liver disease (NAFLD). Concern remains regarding whether the evidence generated under the NAFLD definition can be used for MASLD. We compared the clinical profile and outcomes of NAFLD to MASLD using tertiary care- and population-based data. METHODS: Comparison data were obtained from our NAFLD database and the National Health and Nutrition Examination Survey (NHANES III). Clinical profiles and non-invasive tests (enhanced liver fibrosis [ELF] score, fibrosis-4 index [FIB-4] and vibration-controlled transient elastography) were compared. Mortality data were obtained from NHANES-National Death Index. All-cause mortality was assessed by Cox proportional hazards regression models and cause-specific mortality by competing risk analysis. RESULTS: There were 6,429 patients in the NAFLD database (age: 54 ± 12 years, 42% male, BMI 35.4 ± 8.3, waist circumference 112 ± 17 cm, 52% type 2 diabetes). Average scores for ELF, FIB-4 and liver stiffness were 9.6 ± 1.2, 1.69 ± 1.24,14.0 ± 11.8 kPa, respectively; 99% met MASLD criteria; 95% met MASLD on BMI only. Predictive accuracy of ELF and FIB-4 were identical between MASLD and NAFLD. We included 12,519 eligible participants from NHANES (age 43.00 years, 47.38% male, 22.70% obese, 7.28% type 2 diabetes, 82.51% ≥1 cardiometabolic criteria). Among the NHANES study population, there was excellent concordance between MASLD and NAFLD diagnoses: Cohen's kappa coefficient: 0.968 (95% CI 0.962-0.973) with 5.29% of NAFLD cases not meeting MASLD criteria. After a median follow-up of 22.83 years, there were no mortality differences between MASLD and NAFLD diagnoses (p values ≥0.05). CONCLUSIONS: NAFLD and MASLD are similar except individuals with MASLD seem to be older with slightly higher mortality risk, likely owing to cardiometabolic risk factors. Clinical profiles and non-invasive test thresholds were also identical. These data provide evidence that NAFLD and MASLD terminologies can be used interchangeably. For the small proportion of patients with NAFLD who do not meet MASLD criteria, further consideration is needed. IMPACT AND IMPLICATIONS: In June 2023, new terminology (MASLD) was adopted to replace the term NAFLD as a means to better describe what the liver disease is rather than what it is not, as well as to potentially reduce stigma. Given that MASLD requires at least one cardiometabolic risk factor, questions were raised as to whether this change in the definition would nullify the similarities between NAFLD and MASLD and require new evidence to be generated for MASLD. We used our NAFLD database and a US population-based database to show that the vast majority of patients with NAFLD fulfill criteria for MASLD. Non-invasive tests performed similarly in both groups. Mortality risk was slightly higher in those with MASLD, which is attributed to the presence of cardiometabolic risks. These results provide evidence that data generated in the past three decades for NAFLD can be used interchangeably for MASLD.

Evaluating dynamic and predictive discrimination for recurrent event models: use of a time-dependent C-index.

Interest in analyzing recurrent event data has increased over the past few decades. One essential aspect of a risk prediction model for recurrent event data is to accurately distinguish individuals with different risks of developing a recurrent event. Although the concordance index (C-index) effectively evaluates the overall discriminative ability of a regression model for recurrent event data, a local measure is also desirable to capture dynamic performance of the regression model over time. Therefore, in this study, we propose a time-dependent C-index measure for inferring the model's discriminative ability locally. We formulated the C-index as a function of time using a flexible parametric model and constructed a concordance-based likelihood for estimation and inference. We adapted a perturbation-resampling procedure for variance estimation. Extensive simulations were conducted to investigate the proposed time-dependent C-index's finite-sample performance and estimation procedure. We applied the time-dependent C-index to three regression models of a study of re-hospitalization in patients with colorectal cancer to evaluate the models' discriminative capability.

Clinicopathological concordance of mucocutaneous manifestations in people living with HIV: A cross-sectional study.

OBJECTIVE: To describe the frequency and clinicopathological concordance of mucocutaneous manifestations in people living with HIV (PLWH) and its correlation with CD4+ T lymphocyte count and HIV viral load. METHODS: Cross-sectional study of patients diagnosed with HIV infection who underwent skin biopsy for histopathological study from 1992 to 2022. Skin diseases were categorized as opportunistic and sexually transmitted infections, inflammatory dermatoses, benign cutaneous neoplasms, and premalignant and malignant cutaneous neoplasms. Clinicopathological concordance was classified as complete, partial or discordant. Frequency of skin diseases are presented by category and according to lymphocyte CD4+ count and HIV viral load. RESULTS: A total of 659 patients were included of whom 88.5% (n = 583) were male. The most frequent diagnostic category was opportunistic or sexually transmitted infections in 34% (n = 224) and the most frequently found condition was Kaposi sarcoma in 17% (n = 112). Clinicopathological concordance was complete in 53.7% (n = 354) of cases, partial in 26.7% (n = 176) and discordant in 19.6% (n = 129). Among the 282 patients with available serological data, 58.9% (n = 166), 23.8% (n = 67) and 17.4% (n = 49) had CD4+ counts below 200, between 200 and 499, and above 500 cells/µl, respectively. CONCLUSIONS: Although there is a high variability in skin conditions which people with HIV may present, there was a high rate of clinicopathological concordance (80.4%). We emphasize the importance of diagnostic skin biopsies due to their diverse morphological presentation. The frequency of skin diseases in PLWH depending on different clinical settings should aid the clinician in reaching an adequate diagnosis in this population.

A pilot study of US HTC physical therapists' concordance of PT MASAC recommendations and educational needs.

INTRODUCTION: Physical therapists (PTs) are essential providers within the Hemophilia Treatment Centers (HTCs) team caring for persons with inherited blood disorders (PWBD). OBJECTIVE: Little is known regarding PTs understanding and concordance of MASAC PT Recommendations (MASAC#238), educational resources used to maintain competency and support for a mentorship programme. METHODS: PTs at federally funded HTCs were eligible to participate in a descriptive non-validated study exploring: (i) demographics, (ii) educational background, (iii) experience in evaluation and treatment of PWBD, (iv) practice patterns indicative of concordance with MASAC#238 and (v) opinion regarding PT mentorship. RESULTS: Respondents experience caring for PWBD ranged 1-36 years, treating both adults and children. Although most acknowledged awareness of MASAC#238, dropout (14/44, 31.8%) was noted; 28/30 (93.3%) who continued were aware of the recommendations. Level of concordance with MASAC#238 varied (range 64.3%-96.2%) regarding: signs/symptoms, treatment of muscle/joint bleeding and pre/post synovectomy and knee replacement treatment. Many PTs identified patients as individual and unique, thus not all recommendations may apply. PTs utilised available educational programmes. No relationships were noted regarding years of practice, education and years caring for PWBD. All respondents favoured a mentorship programme citing benefits, but also outlined barriers. CONCLUSIONS: Provision of necessary financial support for optimal function of a full-time PT within the HTC can enhance standards of care for PWBD. Supporting educational opportunities may enhance concordance with current MASAC PT Recommendations. Respondents valued development of a structured, hands-on mentorship programme. MASAC#23 has recently been updated in May 2023 to MASAC#275.

A PSMA PET/CT-based risk model for prediction of concordance between targeted biopsy and combined biopsy in detecting prostate cancer.

PURPOSE: This study is to investigate the diagnostic value of 68Ga-PSMA-11 in improving the concordance between mpMRI-TB and combined biopsy (CB) in detecting PCa. METHODS: 115 consecutive men with 68Ga-PSMA-11 PET/CT prior to prostate biopsy were included for analysis. PSMA intensity, quantified as maximum standard uptake value (SUVmax), minimum apparent diffusion coefficient (ADCmin) and other clinical characteristics were evaluated relative to biopsy concordance using univariate and multivariate logistic regression analyses. A prediction model was developed based on the identified parameters, and a dynamic online diagnostic nomogram was constructed, with its discrimination evaluated through the area under the ROC curve (AUC) and consistency assessed using calibration plots. To assess its clinical applicability, a decision curve analysis (DCA) was performed, while internal validation was conducted using bootstrapping methods. RESULTS: Concordance between mpMRI-TB and CB occurred in 76.5% (88/115) of the patients. Multivariate logistic regression analyses performed that SUVmax (OR= 0.952; 95% CI 0.917-0.988; P= 0.010) and ADCmin (OR= 1.006; 95% CI 1.003-1.010; P= 0.001) were independent risk factors for biopsy concordance. The developed model showed a sensitivity, specificity, accuracy and AUC of 0.67, 0.78, 0.81 and 0.78 in the full sample. The calibration curve demonstrated that the nomogram's predicted outcomes closely resembled the ideal curve, indicating consistency between predicted and actual outcomes. Furthermore, the decision curve analysis (DCA) highlighted the clinical net benefit achievable across various risk thresholds. These findings were reinforced by internal validation. CONCLUSIONS: The developed prediction model based on SUVmax and ADCmin showed practical value in guiding the optimization of prostate biopsy pattern. Lower SUVmax and Higher ADCmin values are associated with greater confidence in implementing mono-TB and safely avoiding SB, effectively balancing benefits and risks.

Extending the DeLong algorithm for comparing areas under correlated receiver operating characteristic curves with missing data.

A nonparametric method proposed by DeLong et al in 1988 for comparing areas under correlated receiver operating characteristic curves is used widely in practice. However, the DeLong method as implemented in popular software quietly deletes individuals with any missing values, yielding potentially invalid and/or inefficient results. We simplify the DeLong algorithm using ranks and extend it to accommodate missing data by using a mixed model approach for multivariate data. Simulation results demonstrate the validity and efficiency of our procedure for data missing at random. We illustrate our proposed procedure in SAS, Stata, and R using the original DeLong data.

Imaging Concordance With Vein Sampling for Primary Aldosteronism: A Cohort Study and Literature Review.

INTRODUCTION: Adrenal venous sampling (AVS) is used to distinguish unilateral from bilateral aldosterone hypersecretion as a cause of primary aldosteronism (PA). Unilateral disease is treated with adrenalectomy and bilateral hypersecretion managed medically. METHODS: We performed a single institution retrospective cohort study of adult patients undergoing adrenalectomy for PA from July 2013 to June 2022. Concordance of imaging findings with AVS was evaluated. Statistical analysis was performed with Mann-Whitney U and chi-squared Fisher's exact. Literature review performed via triple method search strategy. RESULTS: Twenty-one patients underwent AVS and adrenalectomy for PA. Two patients did not have imaging findings and 19 were localized with an adenoma. For patients with image localization, AVS was concordant in nine, discordant in four, and nondiagnostic in six. For patients with discordant findings, age range was 35.8 to 72.4 y compared with concordant patient age range of 49.8 to 71.7 y. Overall discordance between imaging results and AVS was 40%. The aldosterone level was associated with concordance with a median of 52 ng/dL compared with 26 ng/dL if discordant (P = 0.002). There was a significant reduction in antihypertensive medications for the entire cohort from a median of three medications (interquartile range 2-4) to 1 medication (interquartile range 1-2), P < 0.001. CONCLUSIONS: In this cohort, 40% of patients with selective AVS had discordant imaging and AVS results. Aldosterone level was associated with concordance. Hypertension was significantly improved with a median decrease of two antihypertensives. Our results support performance of AVS on all candidates for adrenalectomy for PA.

Association of surgeon-patient sex concordance with postoperative outcomes following complex cancer surgery.

BACKGROUND AND OBJECTIVES: Sex concordance may impact the therapeutic relationship and provider-patient interactions. We sought to define the association of surgeon-patient sex concordance on postoperative patient outcomes following complex cancer surgery. METHODS: Patients who underwent surgery for lung, breast, hepato-pancreato-biliary, or colorectal cancer between 2014 and 2020 were identified from the Medicare Standard Analytic Files. The impact of surgeon-patient sex concordance or discordance on achieving an optimal postoperative textbook outcome (TO) was assessed using multivariable logistic regression. RESULTS: Among 495 628 patients, 241 938 (48.8%) patients were sex concordant with their surgeon while 253 690 (51.2%) patients were sex discordant. Sex discordance between surgeon and patient was associated with a decreased likelihood to achieve a postoperative TO (odds ratio [OR]: 0.95, 95% CI: 0.93-0.97; p < 0.001). Sex discordance was associated with a higher risk of complications (OR: 1.05, 95% CI: 1.03-1.07; p < 0.001) and 90-day mortality (OR: 1.05, 95% CI: 1.01-1.09; p = 0.011). Of note, male patients treated by female surgeons (OR: 0.96, 95% CI: 0.93-0.99; p = 0.017) had a similar lower likelihood to achieve a TO as female patients treated by male surgeons (OR: 0.90, 95% CI: 0.86-0.93; p < 0.001). CONCLUSIONS: Sex discordance was associated with a reduced likelihood of achieving an "optimal" postoperative course following complex cancer surgery.

Gradient synchronization for multivariate functional data, with application to brain connectivity.

Quantifying the association between components of multivariate random curves is of general interest and is a ubiquitous and basic problem that can be addressed with functional data analysis. An important application is the problem of assessing functional connectivity based on functional magnetic resonance imaging (fMRI), where one aims to determine the similarity of fMRI time courses that are recorded on anatomically separated brain regions. In the functional brain connectivity literature, the static temporal Pearson correlation has been the prevailing measure for functional connectivity. However, recent research has revealed temporally changing patterns of functional connectivity, leading to the study of dynamic functional connectivity. This motivates new similarity measures for pairs of random curves that reflect the dynamic features of functional similarity. Specifically, we introduce gradient synchronization measures in a general setting. These similarity measures are based on the concordance and discordance of the gradients between paired smooth random functions. Asymptotic normality of the proposed estimates is obtained under regularity conditions. We illustrate the proposed synchronization measures via simulations and an application to resting-state fMRI signals from the Alzheimer's Disease Neuroimaging Initiative and they are found to improve discrimination between subjects with different disease status.

Correlates of concordance between self-reported and lab-confirmed viral load among Black and Latine men who have sex with men (BLMSM) living with HIV in New York City.

Sustained viral suppression is one of the four strategies in the U.S. Department of Health and Human Services' (HHS) plan to end the HIV epidemic in the United States. Individuals living with HIV must understand their viral load accurately for this strategy to be effective. We conducted cross-sectional analyses using baseline data from the NNHIV longitudinal study among men who have sex with men (MSM) living with HIV in New York City to identify factors associated with concordant knowledge between self-reported and lab-confirmed viral load. Of 164 Black and/or Latine participants, 67% (n = 110) reported that their viral load was undetectable, however lab tests showed only 44% (n = 72) had an undetectable viral load (<20 copies/ml). Overall, 62% of the sample (n = 102) had concordant HIV viral load knowledge (agreement of self-reported and lab viral load). In multivariable regression, those with unstable housing (PR = 0.52, 0.30-0.92) and those who had higher levels of beliefs of racism in medicine scale (PR = 0.76, 0.59-0.97) were less likely to have concordant knowledge. Our study underscores the need for implementing measures to improve viral load knowledge, U = U messaging, and strategies to achieve and maintain undetectable viral load status to reduce the burden of HIV at the population level.

Effect of preoperative chemotherapy on the histopathological classification of gastric cancer.

BACKGROUND: In the era of individualized gastric cancer (GC) treatment, accurate determination of histological subtype becomes increasingly relevant. As yet, it is unclear whether preoperative chemotherapy may affect the histological subtype. The aim of this study was to assess concordance in histological subtype between pretreatment biopsies and surgical resection specimens before and after the introduction of perioperative treatment. METHODS: Histological subtype was centrally determined in paired GC biopsies and surgical resection specimens of patients treated with either surgery alone (SA) in the Dutch D1/D2 study or with preoperative chemotherapy (CT) in the CRITICS trial. The histological subtype as determined in the resection specimen was considered the gold standard. Concordance rates and sensitivity and specificity of intestinal, diffuse, mixed, and "other" subtypes of GC were analyzed. RESULTS: In total, 105 and 515 pairs of GC biopsies and resection specimens of patients treated in the SA and CT cohorts, respectively, were included. Overall concordance in the histological subtype was 72% in the SA and 74% in the CT cohort and substantially higher in the diffuse subtype (83% and 86%) compared to the intestinal (70% and 74%), mixed (21% and 33%) and "other" subtypes (54% and 54%). In the SA cohort, sensitivities and specificities were 0.88 and 0.71 in the intestinal, 0.67 and 0.93 in the diffuse, 0.20 and 0.98 in the mixed, and 0.50 and 0.93 in the "other" subtypes, respectively. CONCLUSION: Our results suggest that accurate determination of histological subtype on gastric cancer biopsies is suboptimal but that the impact of preoperative chemotherapy on histological subtype is negligible.

A Minimal Approach to Demonstrate Concordance of Digital and Conventional Microscopy in Toxicologic Pathology.

Digitalization of pathology workflows has undergone a rapid evolution and has been widely established in the diagnostic field but remains a challenge in the nonclinical safety context due to lack of regulatory guidance and validation experience for good laboratory practice (GLP) use. One means to demonstrate that digital slides are fit for purpose, that is, provide sufficient quality for pathologists to reach a diagnosis, is conduction of comparison studies, which have been published both, for veterinary and human diagnostic pathology, but not for toxicologic pathology. Here, we present an approach that uses study material from nonclinical safety studies and that allows for the statistical comparison of concordance rates for glass and digital slide evaluation while minimizing time and effort for the involved personnel. Using a benchmark study design, we demonstrate that evaluation of digital slides fits the purpose of nonclinical safety evaluation. These results add to reports of successful workflow validations and support the full adaptation of digital pathology in the regulatory field.

Quality control and external quality assessment for the independent clinic-based evaluation of point-of-care testing to detect Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis in eight countries.

BACKGROUND: Sexually transmitted infections caused by Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) remain significant global health problems. The World Health Organization (WHO) has recently conducted a multi-faceted, multi-country validation study (ProSPeRo), which included an evaluation of the Xpert CT/NG and Xpert TV assays on the GeneXpert system (Cepheid, Sunnyvale, Ca., USA) in clinic-based settings across eight countries. To support the study, a training and quality management system was implemented and evaluated. METHODS: A comprehensive training program for the study was developed. Quality control (QC) and external quality assessment (EQA) samples were provided by an accredited quality assurance provider. QC testing was conducted at 14 point-of-care testing (POCT) clinics, while EQA samples were tested by the POCT sites and a reference laboratory supporting each clinic. RESULTS: For QC testing, concordance with the expected results for CT and NG was > 99% and rates of unsuccessful tests were < 4%. For TV testing, concordance was similar (97%), but rates of unsuccessful tests were high (18%), particularly in the 'TV negative' sample. For EQA testing initially conducted in 2018, concordance was 100% for CT and NG, and 90% for TV for the reference laboratory group (which used non-GeneXpert systems). Concordance for the POCT group was also high (> 94%) for all analytes, but this cohort (which used GeneXpert systems) exhibited a high rate of unsuccessful TV tests. All but one of these unsuccessful tests was subcategorised as 'invalid'. CONCLUSIONS: The high level of concordance for QC and EQA testing confirm that the trained operators at the POC clinical sites were competent to conduct POC testing and that the training and quality systems implemented for the ProSPeRo study were effective. The quality materials used were satisfactory for CT and NG but exhibited poor performance for TV testing on the GeneXpert system. The WHO should continue to work with industry and EQA providers to provide improved materials that are reliable, stable and cost effective for quality management, as it seeks to rollout molecular-based STI POCT in non-laboratory-based settings. TRIAL REGISTRATION: Ethics approval to conduct the ProSPeRo study was granted by the WHO Ethics Review Committee.