Search

BackgroundUnderstanding the characteristics of multiparametric MRI (mpMRI) in patients from different racial/ethnic backgrounds is important for reducing the observed gaps in clinical outcomes.PurposeTo investigate the diagnostic performance of mpMRI and quantitative MRI parameters of prostate cancer (PCa) in African American (AA) and matched White (W) men.Study typeRetrospective.SubjectsOne hundred twenty-nine patients (43 AA, 86 W) with histologically proven PCa who underwent mpMRI before radical prostatectomy.Field strength/sequence3.0 T, T2-weighted turbo spin echo imaging, a single-shot spin-echo EPI sequence diffusion-weighted imaging, and a gradient echo sequence dynamic contrast-enhanced MRI with an ultrafast 3D spoiled gradient-echo sequence.AssessmentThe diagnostic performance of mpMRI in AA and W men was assessed using detection rates (DRs) and positive predictive values (PPVs) in zones defined by the PI-RADS v2.1 prostate sector map. Quantitative MRI parameters, including Ktrans and ve of clinically significant (cs) PCa (Gleason score ≥ 7) tumors were compared between AA and W sub-cohorts after matching age, prostate-specific antigen (PSA), and prostate volume.Statistical testsWeighted Pearson's chi-square and Mann-Whitney U tests with a statistically significant level of 0.05 were used to examine differences in DR and PPV and to compare parameters between AA and matched W men, respectively.ResultsA total number of 264 PCa lesions were identified in the study cohort. The PPVs in the peripheral zone (PZ) and posterior prostate of mpMRI for csPCa lesions were significantly higher in AA men than in matched W men (87.8% vs. 68.1% in PZ, and 89.3% vs. 69.6% in posterior prostate). The Ktrans of index csPCa lesions in AA men was significantly higher than in W men (0.25 ± 0.12 vs. 0.20 ± 0.08 min-1; P

BackgroundMultiparametric MRI (mpMRI) has shown a substantial impact on prostate cancer (PCa) diagnosis. However, the understanding of the spatial correlation between mpMRI performance and PCa location is still limited.PurposeTo investigate the association between mpMRI performance and tumor spatial location within the prostate using a prostate sector map, described by Prostate Imaging Reporting and Data System (PI-RADS) v2.1.Study typeRetrospective.SubjectsOne thousand one hundred forty-three men who underwent mpMRI before radical prostatectomy between 2010 and 2022.Field strength/sequence3.0 T. T2-weighted turbo spin-echo, a single-shot spin-echo EPI sequence for diffusion-weighted imaging, and a gradient echo sequence for dynamic contrast-enhanced MRI sequences.AssessmentIntegrated relative cancer prevalence (rCP), detection rate (DR), and positive predictive value (PPV) maps corresponding to the prostate sector map for PCa lesions were created. The relationship between tumor location and its detection/missing by radiologists on mpMRI compared to WMHP as a reference standard was investigated.Statistical testsA weighted chi-square test was performed to examine the statistical differences for rCP, DR, and PPV of the aggregated sectors within the zone, anterior/posterior, left/right prostate, and different levels of the prostate with a statistically significant level of 0.05.ResultsA total of 1665 PCa lesions were identified in 1143 patients, and from those 1060 lesions were clinically significant (cs)PCa tumors (any Gleason score [GS] ≥7). Our sector-based analysis utilizing weighted chi-square tests suggested that the left posterior part of PZ had a high likelihood of missing csPCa lesions at a DR of 67.0%. Aggregated sector analysis indicated that the anterior or apex locations in PZ had the significantly lowest csPCa detection at 67.3% and 71.5%, respectively.Data conclusionSpatial characteristics of the per-lesion-based mpMRI performance for diagnosis of PCa were studied. Our results demonstrated that there is a spatial correlation between mpMRI performance and locations of PCa on the prostate.Evidence level4 TECHNICAL EFFICACY: Stage 2.

Opinion statementPSMA-PET has been a practice-changing imaging biomarker for the management of men with PCa. Research suggests improved accuracy over conventional imaging and other PET radiotracers in many contexts. With multiple approved PSMA-targeting radiotracers, PSMA PET will become even more available in clinical practice. Its increased use requires an understanding of the prospective data available and caution when extrapolating from prior trial data that utilized other imaging modalities. Future trials leveraging PSMA PET for treatment optimization and management decision-making will ultimately drive its clinical utility.

Abstract The objective of study was to characterize HPV in vaginal samples from women being seen at the Center for Reproductive Medicine and Infertility at Weill Cornell Medicine before and following ovarian stimulation. A total of 29 women made samples available for analysis by viral metagenomics. Eighteen women were HPV-positive, six (33.3%) at their initial visit and 15 (83.3%) following hormone stimulation (p = 0.0059). Pairwise comparison of nucleotide sequences and phylogenetic analysis showed the classification sequences into two genera: Alphapapillomavirus and Gammapapillomavirus. Sequences were from 8 HPV types: HPV 51 (n = 2), HPV 68 (n = 1), HPV 83 (n = 9), HPV 84 (n = 2), HPV 121 (n = 6), HPV 175 (n = 1) and HPV 190 (n = 1). Additionally, C16b and C30 likely represent new types. In summary, multiple HPV types are present in the vagina of reproductive age women and are induced by hormone used to stimulate ovulation.

Abstract Introduction Medical financial hardship in the United States is a growing public health concern. This study aims to assess the south vs. non-south disparities in medical financial hardship among US adults of different generations – Boomers (born between 1946 and 1964), Generation X (born between 1965 and 1980), and the Millennials (born between 1981 and 1996) across periods pre- and post- Affordable Care Act (ACA). Methods This observational study utilizes data from multiple waves of the National Health Interview Survey (NHIS) split into three periods: pre–ACA (2011–2013), ii) post ACA (2015–2018), and iii) COVID-19 pandemic (2021–2022). Multivariable logistic regressions were fitted, separately for each generation in each period, to compare the extent of medical financial hardship among those from South to rest of the US, and Karlson-Holm-Breen (KHB) decomposition was applied to analyze whether there was a mediating impact of health insurance coverage. Results Adults living in the South were more likely to experience medical financial hardship in all three periods. Residing in the South was associated with 1.7 to 2.6% points (pp) higher probability of medical financial hardship among boomers, 1.8 to 4.0 pp among generation Xers, and 1.7 to 2.8 pp among millennials. The relationship was robust after accounting for chronic comorbidities, sociodemographic and socioeconomic attributes and was partially mediated through differences in health insurance coverage. Conclusions The problem of medical financial hardship has been deeply rooted in the South across generations, which was partly attributable to the regional differences in health insurance coverage.

This study sought to investigate sixteen New Zealand primary student teachers in the second year of their three-year Bachelor of Teaching (Primary) initial teacher education (ITE) programme. Specifically, how these participating student teachers planned for science, technology, and the arts as they worked to be both more effective and culturally responsive teachers. This study employed ethnomethodology and symbolic interactionism to generate narratives of these student teachers' lived experiences. As part of their programme, these student teachers engaged in reflection-on action to inform reflection-for action as part of peer reflection groups. The findings of this study contributed directly to programme academic development in how to supports student teachers to learn how to become resilient and successful as they negotiate the intersections of being students, teachers, content, pedagogy, and professional expectations in their learning to teach journeys.

Abstract Background Lucilia cuprina (Wiedemann, 1830) (Diptera: Calliphoridae) is the main causative agent of flystrike of sheep in Australia and New Zealand. Female flies lay eggs in an open wound or natural orifice, and the developing larvae eat the host’s tissues, a condition called myiasis. To improve our understanding of host-seeking behavior, we quantified gene expression in male and female antennae based on their behavior. Methods A spatial olfactometer was used to evaluate the olfactory response of L. cuprina mated males and gravid females to fresh or rotting beef. Antennal RNA-Seq analysis was used to identify sensory receptors differentially expressed between groups. Results Lucilia cuprina females were more attracted to rotten compared to fresh beef (> fivefold increase). However, males and some females did not respond to either type of beef. RNA-Seq analysis was performed on antennae dissected from attracted females, non-attracted females and males. Transcripts encoding sensory receptors from 11 gene families were identified above a threshold (≥ 5 transcript per million) including 49 ATP-binding cassette transporters (ABCs), two ammonium transporters (AMTs), 37 odorant receptors (ORs), 16 ionotropic receptors (IRs), 5 gustatory receptors (GRs), 22 odorant-binding proteins (OBPs), 9 CD36-sensory neuron membrane proteins (CD36/SNMPs), 4 chemosensory proteins (CSPs), 4 myeloid lipid-recognition (ML) and Niemann-Pick C2 disease proteins (ML/NPC2), 2 pickpocket receptors (PPKs) and 3 transient receptor potential channels (TRPs). Differential expression analyses identified sex-biased sensory receptors. Conclusions We identified sensory receptors that were differentially expressed between the antennae of both sexes and hence may be associated with host detection by female flies. The most promising for future investigations were as follows: an odorant receptor (LcupOR46) which is female-biased in L. cuprina and Cochliomyia hominivorax Coquerel, 1858; an ABC transporter (ABC G23.1) that was the sole sensory receptor upregulated in the antennae of females attracted to rotting beef compared to non-attracted females; a female-biased ammonia transporter (AMT_Rh50), which was previously associated with ammonium detection in Drosophila melanogaster Meigen, 1830. This is the first report suggesting a possible role for ABC transporters in L. cuprina olfaction and potentially in other insects. Graphical Abstract

Abstract The calcium calmodulin protein kinase II (CaMKII) is a multi-subunit ring assembly with a central hub formed by the association domains. There is evidence for hub polymorphism between and within CaMKII isoforms, but the link between polymorphism and subunit exchange has not been resolved. Here, we present near-atomic resolution cryogenic electron microscopy (cryo-EM) structures revealing that hubs from the α and β isoforms, either standalone or within an β holoenzyme, coexist as 12 and 14 subunit assemblies. Single-molecule fluorescence microscopy of Venus-tagged holoenzymes detects intermediate assemblies and progressive dimer loss due to intrinsic holoenzyme lability, and holoenzyme disassembly into dimers upon mutagenesis of a conserved inter-domain contact. Molecular dynamics (MD) simulations show the flexibility of 4-subunit precursors, extracted in-silico from the β hub polymorphs, encompassing the curvature of both polymorphs. The MD explains how an open hub structure also obtained from the β holoenzyme sample could be created by dimer loss and analysis of its cryo-EM dataset reveals how the gap could open further. An assembly model, considering dimer concentration dependence and strain differences between polymorphs, proposes a mechanism for intrinsic hub lability to fine-tune the stoichiometry of αβ heterooligomers for their dynamic localization within synapses in neurons.

Plasma cell-free DNA (cfDNA) is a noninvasive biomarker for cell death of all organs. Deciphering the tissue origin of cfDNA can reveal abnormal cell death because of diseases, which has great clinical potential in disease detection and monitoring. Despite the great promise, the sensitive and accurate quantification of tissue-derived cfDNA remains challenging to existing methods due to the limited characterization of tissue methylation and the reliance on unsupervised methods. To fully exploit the clinical potential of tissue-derived cfDNA, here we present one of the largest comprehensive and high-resolution methylation atlas based on 521 noncancer tissue samples spanning 29 major types of human tissues. We systematically identified fragment-level tissue-specific methylation patterns and extensively validated them in orthogonal datasets. Based on the rich tissue methylation atlas, we develop the first supervised tissue deconvolution approach, a deep-learning-powered model, cfSort, for sensitive and accurate tissue deconvolution in cfDNA. On the benchmarking data, cfSort showed superior sensitivity and accuracy compared to the existing methods. We further demonstrated the clinical utilities of cfSort with two potential applications: aiding disease diagnosis and monitoring treatment side effects. The tissue-derived cfDNA fraction estimated from cfSort reflected the clinical outcomes of the patients. In summary, the tissue methylation atlas and cfSort enhanced the performance of tissue deconvolution in cfDNA, thus facilitating cfDNA-based disease detection and longitudinal treatment monitoring.

IntroductionCigarette smoking is highly prevalent among Asian American immigrant subgroups. Previously, Asian language telephone Quitline services were only available in California. In 2012, the Centers for Disease Control and Prevention (CDC) funded the national Asian Smokers' Quitline (ASQ) to expand Asian language Quitline services nationally. However, there are relatively few calls to the ASQ from outside California.MethodsThis pilot study assessed the feasibility of two proactive outreach interventions to connect Vietnamese-speaking participants who smoke to the ASQ. Both interventions, 1) proactive telephone outreach with a counselor trained in motivational interviewing (PRO-MI) and 2) proactive telephone outreach with interactive voice response (PRO-IVR), were adapted to be culturally and linguistically appropriate for Vietnamese-speaking participants. Participants were randomly assigned 2:1 to PRO-IVR vs. PRO-MI. Assessments were conducted at baseline and three months post-enrollment. Feasibility indicators were the recruitment rate and initiation of ASQ treatment.ResultsUsing the HealthPartners EHR, a large health system in Minnesota, we identified approximately 343 potentially eligible Vietnamese participants who were mailed invitations letters and baseline surveys with telephone follow-up. We enrolled 86 eligible participants (25% recruitment rate). In the PRO-IVR group 7/58 participants were directly transferred to the ASQ (12% initiation rate) and in the PRO-MI group 8/28 participants were warm transferred to the ASQ (29% initiation rate).ConclusionsThis pilot study demonstrates the feasibility of our recruitment methods and of implementing proactive outreach interventions to promote the initiation of smoking cessation treatment with the ASQ.ImplicationsThis pilot study contributes novel data on the uptake of Asian Smokers' Quitline (ASQ) services among Asian-speaking people who smoke (PWS) with two proactive outreach interventions: 1) proactive telephone outreach with a counselor trained in motivational interviewing (PRO-MI) and 2) proactive telephone outreach with interactive voice response (PRO-IVR). We found that it is feasible to implement these proactive outreach interventions to promote the initiation of ASQ cessation treatment among Vietnamese-language speaking PWS. Future large trials are needed to rigorously compare PRO-MI and PRO-IVR and conduct budget impact analyses to understand the most efficient strategies for incorporation into health system settings.

PurposeThe purpose of this systematic review was to summarize the available data on how surgical management of injuries to the thumb ulnar collateral ligament (UCL) complex affects athletes and their return-to-play (RTP) and postinjury performance metrics in addition to evaluating rehabilitation guidelines.MethodsA systematic search was performed on PubMed and Embase databases for articles on outcomes of surgical treatment of thumb UCL injuries in athletes. Articles with expert recommendations on postoperative management and RTP guidelines were also included separately. Study characteristics were recorded, including sport, RTP rates, and data on performance. Recommendations were summarized by sport. The Methodological Index for Non-Randomized Studies (MINORS) criteria was used to assess methodological quality. The authors also present their recommended return-to-sport algorithm.ResultsTwenty-three articles were included, including 11 with reports on patients and 12 expert opinions on guiding RTP. The mean MINORS score for the applicable studies was 9.4. In the 311 patients included, RTP was 98.1% in aggregate. No performance detriments were noted in athletes after surgery. Thirty-two (10.3%) patients had postoperative complications. The recommendations on timing to RTP vary by sport and author, but all recommended initial thumb protection when returning to sport. Newer techniques, such as suture tape augmentation, suggest the permission for earlier motion.ConclusionsReturn-to-play rates after surgical treatment of thumb UCL injuries are high, with reassuring return to preinjury level of play with few complications. Recommendations for surgical technique have trended toward suture anchors and, now, suture tape augmentation with earlier motion protocols, although rehabilitation guidelines vary by sport and author. Current information on thumb UCL surgery in athletes is limited by the low quality of evidence and expert recommendations.Type of study/level of evidencePrognostic IV.

IntroductionFew studies have evaluated the effects of milk fat globule membrane (MFGM) on microbiota and immune markers in early infant nutrition.MethodsIn this double-blind randomized study, infants (7–18 days of age) received either bovine milk-based infant formula (Control) or similar formula with an added source (5 g/L) of bovine MFGM (INV-MFGM) for 60 days. A reference group received mother’s own human milk over the same period (HM). Oral and stool samples were collected (Baseline and Day 60) to evaluate microbiota, immune markers, and metabolites.ResultsAt Day 60, stool bacterial diversity and richness were higher in formula groups vs HM, as were Bifidobacterium bifidum and B. catenulatum abundance. Compared to HM, stool pH was higher in Control, while acetate, propionate, isovalerate, and total short- and branched-chain fatty acids were higher in INV-MFGM. Butyrate and lactate increased for INV-MFGM from baseline to Day 60. No group differences in oral microbiota or immune markers (α- and β-defensin, calprotectin, or sIgA) were detected, although sIgA increased over time in all study groups. Added bovine MFGM in infant formula modulated stool microbiota and short- and branched-chain fatty acids compared to human milk; changes were modest relative to control formula.DiscussionOverall, distinct patterns of stool metabolites and microbiota development were observed based on early nutrition.Clinical trial registrationClinicalTrials.gov, identifier NCT04059666.

γ-Secretase plays a pivotal role in the central nervous system. Our recent development of genetically encoded Förster resonance energy transfer (FRET)-based biosensors has enabled the spatiotemporal recording of γ-secretase activity on a cell-by-cell basis in live neurons in culture. Nevertheless, how γ-secretase activity is regulated in vivo remains unclear. Here, we employ the near-infrared (NIR) C99 720–670 biosensor and NIR confocal microscopy to quantitatively record γ-secretase activity in individual neurons in living mouse brains. Intriguingly, we uncovered that γ-secretase activity may influence the activity of γ-secretase in neighboring neurons, suggesting a potential ‘cell non-autonomous’ regulation of γ-secretase in mouse brains. Given that γ-secretase plays critical roles in important biological events and various diseases, our new assay in vivo would become a new platform that enables dissecting the essential roles of γ-secretase in normal health and diseases.

Abstract Plants adjust their allocation to different organs based on nutrient supply. In some plant species, symbioses with nitrogen‐fixing bacteria that live in root nodules provide an alternate pathway for nitrogen acquisition. Does access to nitrogen‐fixing bacteria modify plants' biomass allocation? We hypothesized that access to nitrogen‐fixing bacteria would have the same effect on allocation to aboveground versus belowground tissues as access to plentiful soil nitrogen. To test this hypothesis and related hypotheses about allocation to stems versus leaves and roots versus nodules, we conducted experiments with 15 species of nitrogen‐fixing plants in two separate greenhouses. In each, we grew seedlings with and without access to symbiotic bacteria across a wide gradient of soil nitrogen supply. As is common, uninoculated plants allocated relatively less biomass belowground when they had more soil nitrogen. As we hypothesized, nitrogen fixation had a similar effect as the highest level of fertilization on allocation aboveground versus belowground. Both nitrogen fixation and high fertilization led to ~10% less biomass allocated belowground (~10% more aboveground) than the uninoculated, lowest fertilization treatment. Fertilization reduced allocation to nodules relative to roots. The responses for allocation of aboveground tissues to leaves versus stems were not as consistent across greenhouses or species as the other allocation trends, though more nitrogen fixation consistently led to relatively more allocation to leaves when soil nitrogen supply was low. Synthesis: Our results suggest that symbiotic nitrogen fixation causes seedlings to allocate relatively less biomass belowground, with potential implications for competition and carbon storage in early forest development.

Objective: We sought to examine the influence of social needs on the relationship between cancer history and colorectal cancer (CRC) screening utilization among adults in the United States. Methods: We conducted a cross-sectional analysis using data from the 2022 Behavioral Risk Factor Surveillance System. Our outcome of interest was utilization of guideline-concordant CRC screening and exposures of interest were cancer history/levels of social needs. Multivariable logistic regression was performed to examine the association. Results: Among 74,743 eligible adults, a majority did not have a personal history of cancer (87.9 %), had at least one social need (58.4 %), and had undergone CRC screening (72.2 %). In multivariable analysis, a history of cancer was positively associated with use of CRC screening (OR = 1.59, 95 %CI, 1.35 – 1.87). Having at least one social need was associated with lower likelihood of being screened (one social need: OR = 0.85 95 %CI, 0.76 – 0.95; two + social needs: OR = 0.77, 95 % CI, 0.69 – 0.87). When exploring the effects of social needs, adults without a history of cancer who reported at least one need were 12–20 % less likely to be screened for CRC. Conclusions: A personal history of cancer was associated with greater utilization of CRC screening, whilst having at least one social need had lower screening use. Having social needs plays an important role in reducing screening uptake among adults without a history of cancer. Integrated care that considers both cancer history and social needs may have implications for improved adherence of CRC screening recommendations.

Objective: We describe the clinical presentation and ocular viral dynamics in patients with Monkeypox virus-related ophthalmic disease (MPXROD). Methods: In this case series, we investigated five consecutive patients with confirmed mpox, diagnosed through a positive Monkeypox virus (MPXV) Polymerase Chain Reaction (PCR) test and presenting with ocular symptoms. They were referred from the Reference Center for Sexually Transmitted Infections in São Paulo (CRT) to the Uveitis Sector at the Federal University of São Paulo, between August and December 2022. We performed PCR testing on ocular samples and culture supernatants for MPXV in all patients. Viral sequencing was conducted in one of the cases. Results: Replicating MPXV was identified in at least one ocular sample of all patients, between day 31 and day 145 after the onset of skin lesions. All patients presented with keratitis, 3 with uveitis (60%) and two exhibited hypopyon (40%). The onset of ocular symptoms occurred at a mean of 21.2 days after the appearance of the first skin lesion and persisted, on average, for 61,.6 days, with a worsening trend observed until the initiation of tecovirimat treatment. Tecovirimat treatment was administered to all patients, with initiation occurring between 31 and 145 days after the onset of skin lesions. MPXV genome sequencing of an isolate from one patient classified it as belonging to lineage B1 in clade IIb. Conclusion: This study reveals a late onset and persistence of sight threatening ocular disease, along with potential viral infectivity even after systemic resolution in mpox cases. These findings highlight the risk of ongoing transmission from individuals with prolonged ocular manifestations, particularly through ocular discharge.

BackgroundPatients increasingly rely on web-based physician reviews to choose a physician and share their experiences. However, the unstructured text of these written reviews presents a challenge for researchers seeking to make inferences about patients’ judgments. Methods previously used to identify patient judgments within reviews, such as hand-coding and dictionary-based approaches, have posed limitations to sample size and classification accuracy. Advanced natural language processing methods can help overcome these limitations and promote further analysis of physician reviews on these popular platforms. ObjectiveThis study aims to train, test, and validate an advanced natural language processing algorithm for classifying the presence and valence of 2 dimensions of patient judgments in web-based physician reviews: interpersonal manner and technical competence. MethodsWe sampled 345,053 reviews for 167,150 physicians across the United States from Healthgrades.com, a commercial web-based physician rating and review website. We hand-coded 2000 written reviews and used those reviews to train and test a transformer classification algorithm called the Robustly Optimized BERT (Bidirectional Encoder Representations from Transformers) Pretraining Approach (RoBERTa). The 2 fine-tuned models coded the reviews for the presence and positive or negative valence of patients’ interpersonal manner or technical competence judgments of their physicians. We evaluated the performance of the 2 models against 200 hand-coded reviews and validated the models using the full sample of 345,053 RoBERTa-coded reviews. ResultsThe interpersonal manner model was 90% accurate with precision of 0.89, recall of 0.90, and weighted F1-score of 0.89. The technical competence model was 90% accurate with precision of 0.91, recall of 0.90, and weighted F1-score of 0.90. Positive-valence judgments were associated with higher review star ratings whereas negative-valence judgments were associated with lower star ratings. Analysis of the data by review rating and physician gender corresponded with findings in prior literature. ConclusionsOur 2 classification models coded interpersonal manner and technical competence judgments with high precision, recall, and accuracy. These models were validated using review star ratings and results from previous research. RoBERTa can accurately classify unstructured, web-based review text at scale. Future work could explore the use of this algorithm with other textual data, such as social media posts and electronic health records.