Context-specific regulation of cell survival by a miRNA-controlled BIM rheostat.

Knockout of the ubiquitously expressed miRNA-17∼92 cluster in mice produces a lethal developmental lung defect, skeletal abnormalities, and blocked B lymphopoiesis. A shared target of miR-17∼92 miRNAs is the pro-apoptotic protein BIM, central to life-death decisions in mammalian cells. To clarify the contribution of miR-17∼92:Bim interactions to the complex miR-17∼92 knockout phenotype, we used a system of conditional mutagenesis of the nine Bim 3' UTR miR-17∼92 seed matches. Blocking miR-17∼92:Bim interactions early in development phenocopied the lethal lung phenotype of miR-17∼92 ablation and generated a skeletal kinky tail. In the hematopoietic system, instead of causing the predicted B cell developmental block, it produced a selective inability of B cells to resist cellular stress; and prevented B and T cell hyperplasia caused by Bim haploinsufficiency. Thus, the interaction of miR-17∼92 with a single target is essential for life, and BIM regulation by miRNAs serves as a rheostat controlling cell survival in specific physiological contexts.

Direct current stimulation modulates prefrontal cell activity and behaviour without inducing seizure-like firing.

Transcranial direct current stimulation (tDCS) has garnered significant interest for its potential to enhance cognitive functions and as a therapeutic intervention in various cognitive disorders. However, the clinical application of tDCS has been hampered by significant variability in its cognitive outcomes. Furthermore, the widespread use of tDCS has raised concerns regarding its safety and efficacy, particularly in light of our limited understanding of its underlying neural mechanisms at the cellular level. We still do not know 'where', 'when' and 'how' tDCS modulates information encoding by neurons, in order to lead to the observed changes in cognitive functions. Without elucidating these fundamental unknowns, the root causes of its outcome variability and long-term safety remain elusive, challenging the effective application of tDCS in clinical settings. Addressing this gap, our study investigates the effects of tDCS, applied over the dorsolateral prefrontal cortex, on cognitive abilities and individual neuron activity in macaque monkeys performing cognitive tasks. Like humans performing a delayed match-to-sample task, monkeys exhibited practice-related slowing in their responses (within-session behavioural adaptation). Concurrently, there were practice-related changes in simultaneously recorded activity of prefrontal neurons (within-session neuronal adaptation). Anodal tDCS attenuated both these behavioural and neuronal adaptations when compared with sham stimulation. Furthermore, tDCS abolished the correlation between response time of monkeys and neuronal firing rate. At a single-cell level, we also found that following tDCS, neuronal firing rate was more likely to exhibit task-specific modulation than after sham stimulation. These tDCS-induced changes in both behaviour and neuronal activity persisted even after the end of tDCS stimulation. Importantly, multiple applications of tDCS did not alter burst-like firing rates of individual neurons when compared with sham stimulation. This suggests that tDCS modulates neural activity without enhancing susceptibility to epileptiform activity, confirming a potential for safe use in clinical settings. Our research contributes unprecedented insights into the 'where', 'when' and 'how' of tDCS effects on neuronal activity and cognitive functions by showing that modulation of the behaviour of monkeys by the tDCS of the prefrontal cortex is accompanied by alterations in prefrontal cortical cell activity ('where') during distinct trial phases ('when'). Importantly, tDCS led to task-specific and state-dependent alterations in prefrontal cell activities ('how'). Our findings suggest a significant shift from the view that the effects of tDCS are merely attributable to polarity-specific shifts in cortical excitability and instead propose a more complex mechanism of action for tDCS that encompasses various aspects of cortical neuronal activity without increasing burst-like epileptiform susceptibility.

Profiling Humoral Immunity After Mixing and Matching COVID-19 Vaccines Using SARS-CoV-2 Variant Protein Microarrays.

In November 2022, 68% of the population received at least one dose of COVID-19 vaccines. Owing to the ongoing mutations, especially for the variants of concern (VOCs), it is important to monitor the humoral immune responses after different vaccination strategies. In this study, we developed a SARS-CoV-2 variant protein microarray that contained the spike proteins from the VOCs, e.g., alpha, beta, gamma, delta, and omicron, to quantify the binding antibody and surrogate neutralizing antibody. Plasmas were collected after two doses of matching AZD1222 (AZx2), two doses of matching mRNA-1273 (Mx2), or mixing AZD1222 and mRNA-1273 (AZ+M). The results showed a significant decrease of surrogate neutralizing antibodies against the receptor-binding domain in all VOCs in AZx2 and Mx2 but not AZ+M. A similar but minor reduction pattern of surrogate neutralizing antibodies against the extracellular domain was observed. While Mx2 exhibited a higher surrogate neutralizing level against all VOCs compared with AZx2, AZ+M showed an even higher surrogate neutralizing level in gamma and omicron compared with Mx2. It is worth noting that the binding antibody displayed a low correlation to the surrogate neutralizing antibody (R-square 0.130-0.382). This study delivers insights into humoral immunities, SARS-CoV-2 mutations, and mixing and matching vaccine strategies, which may provide a more effective vaccine strategy especially in preventing omicron.

Emphasis of Diversity, Equity, and Inclusion on US Adult Infectious Disease Fellowship Program Websites in the Era of Virtual Recruitment.

Women and underrepresented-in-medicine applicants value a climate for diversity when selecting graduate medical education training programs. Climate may not be accurately represented during virtual recruitment. Optimizing program websites may help overcome this barrier. We reviewed websites for adult infectious disease fellowships that participated in the 2022 National Resident Matching Program for emphasis on diversity, equity, and inclusion (DEI). Fewer than half expressed DEI language in their mission statement or had a dedicated DEI statement or webpage. Programs should consider emphasizing their commitment to DEI prominently on their websites, which may help recruit candidates from diverse backgrounds.

Infectious Diseases Training in the 21st Century: A Glass Half Full or Half Empty?

The percentage of infectious diseases (ID) fellowship positions filled has declined in the last years despite a relatively stable number of applicants. The data are concerning since this could impact an already strained workforce. A recent survey of ID fellowship program directors provides insight into the perceptions of program directors about factors that might have affected the match rate in 2023 and could also be applicable to the recent 2024 match. Here, we discuss the results of this survey and discuss the complex factors that might influence the choice of ID as an specialty. Although concerning, recent fellowship match results provide new opportunities to reassess current models of ID training and design innovative strategies for ID fellowship and education.

Analysis of the Infectious Diseases Fellowship Program Directors Postmatch 2023 Survey.

The 2023 United States infectious diseases (ID) fellowship match resulted in a large percentage of programs with unfilled positions. A survey was sent to ID program directors nationwide to better understand their perceptions on the match. Program directors perceived geography, a small applicant pool, and low specialty pay as contributing factors to the match results. Developing specialized fellowship tracks, increasing funding for the ID trainee pipeline, and national advocacy for higher compensation were identified as areas to focus on to increase the applicant pool. Areas of controversy, such as decreasing the number or size of fellowship programs, require further discussion.

Population-Based Evaluation of Vaccine Effectiveness against SARS-CoV-2 Infection, Severe Illness, and Death, Taiwan.

Taiwan provided several COVID-19 vaccine platforms: mRNA (BNT162b2, mRNA-1273), adenoviral vector-based (AZD1222), and protein subunit (MVC-COV1901). After Taiwan shifted from its zero-COVID strategy in April 2022, population-based evaluation of vaccine effectiveness (VE) became possible. We conducted an observational cohort study of 21,416,151 persons to examine VE against SARS-CoV-2 infection, moderate and severe illness, and death during March 22, 2021-September 30, 2022. After adjusting for age and sex, we found that persons who completed 3 vaccine doses (2 primary, 1 booster) or received MVC-COV1901 as the primary series had the lowest hospitalization incidence (0.04-0.20 cases/100,000 person-days). We also found 95.8% VE against hospitalization for 3 doses of BNT162b2, 91.0% for MVC-COV1901, 81.8% for mRNA-1273, and 65.7% for AZD1222, which had the lowest overall VE. Our findings indicated that protein subunit vaccines provide similar protection against SARS-CoV-2---associated hospitalization as mRNA vaccines and can inform mix-and-match vaccine selection in other countries.

Olaparib for childhood tumors harboring defects in DNA damage repair genes: arm H of the NCI-COG Pediatric MATCH trial.

BACKGROUND: The National Cancer Institute-Children's Oncology Group Pediatric Molecular Analysis for Therapy Choice (MATCH) precision oncology platform trial enrolled children aged 1-21 years with treatment-refractory solid tumors and predefined actionable genetic alterations. Patients with tumors harboring alterations in DNA damage repair (DDR) genes were assigned to receive olaparib. METHODS: Tumor and blood samples were submitted for centralized molecular testing. Tumor and germline sequencing were conducted in parallel. Olaparib was given twice daily for 28-day cycles starting at a dose 30% lower than the adult recommended phase 2 dose (RP2D). The primary endpoint was the objective response. RESULTS: Eighteen patients matched (1.5% of those screened) based on the presence of a deleterious gene alteration in BRCA1/2, RAD51C/D, or ATM detected by tumor sequencing without germline subtraction or analysis of loss of heterozygosity (LOH). Eleven (61%) harbored a germline mutation, with only one exhibiting LOH. Six patients enrolled and received the olaparib starting dose of 135 mg/m2/dose. Two participants were fully evaluable; 4 were inevaluable because <85% of the prescribed dose was administered during cycle 1. There were no dose-limiting toxicities or responses. Minimal hematologic toxicity was observed. CONCLUSION: Most DDR gene alterations detected in Pediatric MATCH were germline, monoallelic, and unlikely to confer homologous recombination deficiency predicting sensitivity to olaparib monotherapy. The study closed due to poor accrual. CLINICALTRIALS.GOV IDENTIFIER: NCT03233204. IRB approved: initial July 24, 2017.

Phase II study of vemurafenib in children and young adults with tumors harboring BRAF V600 mutations: NCI-COG pediatric MATCH trial (APEC1621) Arm G.

BACKGROUND: This is a phase II subprotocol of the NCI-COG Pediatric MATCH study evaluating vemurafenib, a selective oral inhibitor of BRAF V600 mutated kinase, in patients with relapsed or refractory solid tumors harboring BRAF V600 mutations. METHODS: Patients received vemurafenib at 550 mg/m2 (maximum 960 mg/dose) orally twice daily for 28-day cycles until progression or intolerable toxicity. The primary aim was to determine the objective response rate and secondary objectives included estimating progression-free survival and assessing the tolerability of vemurafenib. RESULTS: Twenty-two patients matched to the subprotocol and 4 patients (18%) enrolled. Primary reasons for non-enrollment were ineligibility due to exclusions of low-grade glioma (n = 7) and prior BRAF inhibitor therapy (n = 7). Enrolled diagnoses were one each of histiocytosis, ameloblastoma, Ewing sarcoma, and high-grade glioma, all with BRAF V600E mutations. Treatment was overall tolerable with mostly expected grade 1/2 adverse events (AE). Grade 3 or 4 AE on treatment were acute kidney injury, hyperglycemia, and maculopapular rash. One patient came off therapy due to AE. One patient (glioma) had an objective partial response and remained on protocol therapy for 15 cycles. CONCLUSION: There was a low accrual rate on this MATCH subprotocol, with only 18% of those who matched with BRAFV600 mutations enrolling, resulting in early termination, and limiting study results (ClinicalTrials.gov Identifier: NCT03220035).

Implementing Lattice and Energy Level Matching to Optimize Buried Interfaces for High-Performance Perovskite Solar Cells.

In n-i-p type perovskite solar cells (PSCs), mismatches in energy level and lattice at the buried interface is highly detrimental to device performance. Here, thin PbS interconnect layer in situ coating on the SnO2 surface is grown. The function of PbS at the interface is different from the commonly used function of crystalline seeds in perovskite bulk. The theoretical calculation show that it helps construct an interconnect structure of SnO2/PbS/Perovskite with matched energy level and lattice. This not only increases conductivity of SnO2, but also upshifts Fermi energy levels (EF) of both SnO2 and buried perovskite due to charge transfer and perovskite's internal defect changes. Such a suitable energy level arrangement ensures a better energy level match at the interface, favoring efficient charge transfer and less open circuit voltage (Voc) loss. Additionally, in situ PL reveals that the template effect of PbS enable perovskite grain to grow bottom-up because of their highly matched lattice parameters. This growth mode optimizes buried interface contact and crystallinity of perovskite. Ultimately, after PbS modification, a remarkable power conversion efficiency (PCE) exceeding 24% and better device stability are obtained. This work demonstrates an effective interconnect layers strategy to realize ideal interface contact toward high-performance PSCs.

Colloidal CsBr Nanocrystals Triggered Inorganic Cation and Anion Exchange Enables High-Performance Perovskite Solar Cells.

Achieving longitudinal doping of specific ions by surface treatment remains a challenge for perovskite solar cells, which are often limited by dopant and solvent compatibility. Here, with the flowing environment created by CsBr colloidal nanocrystals, ion exchange is induced on the surface of the perovskite film to enable the homogeneous distribution of Cs+ and gradient distribution of Br- simultaneously at whole depth of the film. Meanwhile, assisted by long-chain organic ligands, the excess PbI2 on the surface of perovskite film is converted to a more stable quasi-2D perovskite, which realizes effective passivation of defects on the surface. As a result, the unfavorable n-type doping on the top surface is suppressed, so that the energy level alignment between perovskite and hole transport layer is optimized. On the basis of co-modification of the surface and the bulk, the PCE of champion device reaches 23.22% with enhanced VOC of 1.12 V. Device maintains 97.12% of the initial PCE in dark ambient air at 1% RH after 1056 h without encapsulation, and 91.56% of the initial PCE under light illumination of 1 sun in N2 atmosphere for more than 200 h. The approach demonstrated here provides an effective strategy for the nondestructive introduction of inorganic ions in perovskite film.

Breast-Conserving Therapy Versus Postmastectomy Breast Reconstruction: Propensity Score-Matched Analysis.

BACKGROUND: Although studies have compared patient-reported outcomes (PROs) after breast conserving-therapy (BCT) and postmastectomy breast reconstruction (PMBR), they often have been confounded by treatment or other factors that complicate a direct comparison. This study aimed to compare PROs after BCT and PMBR by using propensity score-matching analysis. METHODS: Patients who underwent BCT or PMBR between 2010 and 2022 and completed the BREAST-Q were identified. Each BCT patient was matched to a PMBR patient using nearest-neighbor 1:1 matching with replacement for each BREAST-Q time point. Outcomes included all prospectively collected BREAST-Q domains preoperatively, at 6 months, and at 1, 2, and 3 years postoperatively. A 4-point difference was considered clinically meaningful. RESULTS: For this study, 6215 patients (2501 BCT [40.2%] and 3714 PMBR [59.8%] patients) were eligible, and 2616 unique patients were matched. Preoperatively, 463 BCT and 463 PMBR patients were matched for analysis (6 months [443 matched pairs], 1 year [639 matched pairs], 2 years [421 matched pairs], 3 years [254 matched pairs]). At 6 months postoperatively, the BCT patients scored higher on all BREAST-Q domains than the PMBR patients (p < 0.05; differences > 4 points). At 1, 2, and 3 years, the patients who underwent BCT consistently had superior Satisfaction With Breasts, Psychosocial Well-Being, and Sexual Well-Being (p < 0.05), and the differences were clinically meaningful. CONCLUSION: In this statistically powered study, the BCT patients reported higher quality of life than the PMBR patients in early assessment and also through 3 years of follow-up evaluation. Given the equivalency in survival and recurrence outcomes between BCT and PMBR, patients eligible for either surgery should be counseled regarding the superiority of BCT in terms of PROs.

Vascular In-person for Students In the match Trial: An investigation of postinterview site visits to address the limitations of virtual interviews.

PURPOSE: The graduate medical education community implemented virtual residency interviews in response to travel restrictions during the COVID-19 pandemic, and this approach has persisted. Although many residency applicants wish to visit in-person prospective training sites, such opportunities could bias programs toward those who are able to meet this financial burden, exacerbating equity concerns. One proposed solution is to offer applicants the opportunity to visit only after a program's rank list is "locked," avoiding favoritism to applicants who visit, but allowing applicants to experience some of the camaraderie, geography, and local effects of an in-person visit. As debate about the optimal format of residency interviews continues, it is important to investigate whether in-person program visits, completed after program rank list certification, provide meaningful benefits to applicants in the residency match process. METHODS: All vascular programs entering the 2023 integrated vascular surgery residency match were invited to participate. Programs agreed to certify their National Resident Matching Program rank lists by February 1, 2023. Applicants then had the opportunity to visit the programs at which they interviewed. The particulars of the visit were determined by the individual programs. Applicants completed their standard rank list and locked on the standard date: March 1, 2023. Applicants then completed a survey regarding the impact of the visits on their rank order list decision-making. Program directors (PDs) completed a survey regarding their experiences as well. Data were collected using REDCap. RESULTS: Twenty-one of the 74 (28%) programs participated. Nineteen PDs completed the postinterview site visit survey (response rate 90%). Applicants interviewing at the participating programs (n = 112) were informed of the study, offered the opportunity to attend postinterview site visits, and received the survey. Forty-seven applicants responded (response rate 42%). Eighty-six percent of applicants stated that the visit impacted their rank list. Most important factors were esprit de corps of the program (86%), the faculty/trainees/staff (81%), and the physical setting (62%). Seventy-one percent of those participating spent ≤$800 on their visit. Eighty-one percent were satisfied with the process. Twenty-one percent of PDs would have changed their rank list if they could have based on the applicants' in-person visit. Sixty-three percent of the visit sessions cost the programs ≤$500, and 63% were satisfied with the process. CONCLUSIONS: This study is the first to document the impact of in-person site visits by applicants on a graduate medical education match process in one specialty. Our results suggest that this process provides meaningful data to applicants that helped them with their decision-making evidenced by most altering their rank lists, while avoiding some of the critical equity issues that accompany traditional in-person interviews. This may provide a model for future interview processes for residency programs.

On the Unequal Burden of Obesity: Obesity's Adverse Consequences Are Contingent on Regional Obesity Prevalence.

Obesity has adverse consequences for those affected. We tested whether the association between obesity and its adverse consequences is reduced in regions in which obesity is prevalent and whether lower weight bias in high-obese regions can account for this reduction. Studies 1 and 2 used data from the United States (N = 2,846,132 adults across 2,546 counties) and United Kingdom (N = 180,615 adults across 380 districts) that assessed obesity's adverse consequences in diverse domains: close relationships, economic outcomes, and health. Both studies revealed that the association between obesity and its adverse consequences is reduced (or absent) in high-obese regions. Study 3 used another large-scale data set (N = 409,837 across 2,928 U.S. counties) and revealed that lower weight bias in high-obese regions seems to account for (i.e., mediate) the reduction in obesity's adverse consequences. Overall, our findings suggest that obesity's adverse consequences are partly social and, thus, not inevitable.

Internal Medicine Residency Program Applicant Perceptions of the SPLIT Recruitment Model Before and After Universal Virtual Interviews.

BACKGROUND: Enhancing residency recruitment with modifications to interviews has been an area of national interest, further catalyzed by the transition to universal virtual interviewing (UVI). In 2018, our internal medicine residency program redesigned the recruitment process using virtual interviews. OBJECTIVE: Evaluating this recruitment model allows programs to identify applicant perceptions of each component as they consider enhancements. DESIGN: The new model, termed "SPLIT," included separating optional applicant visit days (AVD) from interviews (S), a pre-interview supplemental form (P), learning program information from a dedicated website (L), virtual interviews (I), and flexible timing (remote interview day and site visit) (T). PARTICIPANTS: Applicants for the 2019 to 2023 Match who interviewed at one university-based internal medicine residency program. MAIN MEASURES: After rank list certification and before the annual Match, interviewed applicants were surveyed regarding their perceptions of the SPLIT process. Responses before (2019-2020 Matches) and after (2021-2023 Matches) UVIs were compared. KEY RESULTS: A total of 386 (75%) of 515 respondents favored video interviews. This preference was stronger in the post-UVI group (92%) than in the pre-UVI group (57%) (p < 0.001). In total, 76% of respondents attended an AVD (virtual or in-person). Applicants in the post-UVI group also favored having interviews separated from the AVD (p = 0.006) and optional AVDs (p < 0.001), more than those in the pre-UVI group. In the pre-UVI cohort, those who attended an in-person AVD tended to report a higher program understanding (OR 7.8), satisfaction with SPLIT (OR 2.1), and a better recruitment experience (OR 2.0). CONCLUSIONS: Virtual interviews were highly rated with increased preference following universal adoption. Optional AVDs separated from virtual interviews enhance applicant understanding of the program and were more effective when offered in-person before the pandemic-related restrictions. As programs begin to reintroduce in-person elements, the SPLIT recruitment model offers an innovative approach that addresses applicant and program needs.

Establishment and verification of novel TNM staging system for lung mucinous adenocarcinoma.

BACKGROUND: Lung adenocarcinoma is a high-mortality rate cancer. Within this category, Lung mucinous adenocarcinoma (LMAC) is a rare and distinct subtype of lung adenocarcinoma necessitating further investigation. The study was launched to compare the difference of survival features between LMAC and lung non-mucinous adenocarcinoma (LNMAC) and to investigate the significance and demand for developing a new staging system tailored to LMAC. METHODS: This retrospective study assessed the suitableness of the current staging system for LMAC. It compared the overall survival (OS) between LMAC and LNMAC from 2004 to 2020 (LNMAC: 160,387; LMAC: 6,341) and instituted a novel classification framework for LMAC based on US population. Verification group consisting of patients from two Chinese medical centers from 2010 to 2018 (n = 392) was set to ascertain the applicability of this novel system. The primary endpoint was OS. To minimize the bias, propensity score match (PSM) was employed. Survival analysis and Log-rank test were executed to explore the survival features of LMAC. RESULTS: The results indicated that the existed staging system was not suitable for LMAC. Patients diagnosed with LMAC exhibited a superior OS compared to those with LNMAC in stage IA2 (P < 0.0001), IA3 (P < 0.0001), IB (P = 0.0062), IIA (P = 0.0090), IIB (P = 0.0005). In contrast, a worse OS in stage IVA (P = 0.0103) was found in LMAC patients. The novel classification system proposed for LMAC proved to be highly applicable and demonstrated substantial efficacy, as confirmed by the verification group. CONCLUSION: The newly established classification system was more effective for LMAC, but it necessitates large-scale verification to confirm its applicability and reliability.

Phase-Resolved Functional Lung (PREFUL) MRI May Reveal Distinct Pulmonary Perfusion Defects in Postacute COVID-19 Syndrome: Sex, Hospitalization, and Dyspnea Heterogeneity.

BACKGROUND: Pulmonary perfusion defects have been observed in patients with coronavirus disease 2019 (COVID-19). Currently, there is a need for further data on non-contrast-enhanced MRI in COVID patients. The early identification of heterogeneity in pulmonary perfusion defects among COVID-19 patients is beneficial for their timely clinical intervention and management. PURPOSE: To investigate the utility of phase-resolved functional lung (PREFUL) MRI in detecting pulmonary perfusion disturbances in individuals with postacute COVID-19 syndrome (PACS). STUDY TYPE: Prospective. SUBJECTS: Forty-four participants (19 females, mean age 64.1 years) with PACS and 44 healthy subjects (19 females, mean age 59.5 years). Moreover, among the 44 patients, there were 19 inpatients and 25 outpatients; 19 were female and 25 were male; 18 with non-dyspnea and 26 with dyspnea. FIELD STRENGTH/SEQUENCE: 3-T, two-dimensional (2D) spoiled gradient-echo sequence. ASSESSMENT: Ventilation and perfusion-weighted maps were extracted from five coronal slices using PREFUL analysis. Subsequently, perfusion defect percentage (QDP), ventilation defect percentage (VDP), and ventilation-perfusion match healthy (VQM) were calculated based on segmented lung parenchyma ventilation and perfusion-weighted maps. Additionally, clinical features, including demographic data (such as sex and age) and serum biomarkers (such as D-dimer levels), were evaluated. STATISTICAL TESTS: Spearman correlation coefficients to explore relationships between clinical features and QDP, VDP, and VQM. Propensity score matching analysis to reduce the confounding bias between patients with PACS and healthy controls. The Mann-Whitney U tests and Chi-squared tests to detect differences between groups. Multivariable linear regression analyses to identify factors related to QDP, VDP, and VQM. A P-value <0.05 was considered statistically significant. RESULTS: QDP significantly exceeded that of healthy controls in individuals with PACS (39.8% ± 15.0% vs. 11.0% ± 4.9%) and was significantly higher in inpatients than in outpatients (46.8% ± 17.0% vs. 34.5% ± 10.8%). Moreover, males exhibited pulmonary perfusion defects significantly more frequently than females (43.9% ± 16.8% vs. 34.4% ± 10.2%), and dyspneic participants displayed significantly higher perfusion defects than non-dyspneic patients (44.8% ± 15.8% vs. 32.6% ± 10.3%). QDP showed a significant positive relationship with age (ß = 0.50) and D-dimer level (ß = 0.72). DATA CONCLUSION: PREFUL MRI may show pulmonary perfusion defects in patients with PACS. Furthermore, perfusion impairments may be more pronounced in males, inpatients, and dyspneic patients. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

The golden tickets: impact of preference signaling on obstetrics and gynecology residency applicants.

BACKGROUND: With the residency selection process becoming more competitive and programs receiving unprecedented numbers of applications, some specialties have introduced preference signaling in an attempt to help applicants target programs of interest. In the 2022-2023 application cycle, obstetrics and gynecology also introduced a 2-tiered system with a limited number of gold signals (n=3) and silver signals (n=15). OBJECTIVE: Given the novelty of preference signaling in the obstetrics and gynecology residency application process, this study aimed to (1) assess the effect of signals on interview offers and match and (2) discuss applicant attitudes toward this preference signaling system. STUDY DESIGN: This was a voluntary cross-sectional survey study conducted in April 2023 that was open to all fourth-year medical students who applied to an obstetrics and gynecology residency in the United States. Self-reported demographics, signaling, interview, and match data were collected. In addition, students were asked about attitudes toward signaling on a 5-point Likert scale. RESULTS: Of the 1507 applicants who entered an obstetrics and gynecology residency via match or Supplemental Offer and Acceptance Program process, 969 (64.3%) completed the survey. Moreover, an additional 22 applicants who did not match responded to the survey. More respondents used all 3 gold tokens (98.3%) and all 15 silver tokens (94.3%). The mean number of applications sent was 74.3±35.1, and the mean number of interviews received per applicant was 12.8±6.6. The interviews or token yields were 64.0%±31.5% for gold tokens, 43.8%±23.1% for silver tokens, and 9.8%±10.0% for no token. Of the survey respondents, 340/951 (35.8%) matched to a gold token program, 338/951 (35.5%) matched to a silver token program, and 244/951 (25.7%) matched to a nontoken program. Furthermore, 499/951 applicants (52.5%) reported feeling slightly positive or very positive about signaling. CONCLUSION: Most obstetrics and gynecology applicants in this survey participated in preference signaling. Gold and silver tokens were associated with high ratios of interview invitations compared with no token. However, the overall number of applications did not decrease in the 2022-2023 cycle, and only half of survey respondents reported feeling positive about the signaling process. These results can inform program directors and students about application number and strategy in upcoming cycles.

Categorical linkage-data analysis.

Analysis of integrated data often requires record linkage in order to join together the data residing in separate sources. In case linkage errors cannot be avoided, due to the lack a unique identity key that can be used to link the records unequivocally, standard statistical techniques may produce misleading inference if the linked data are treated as if they were true observations. In this paper, we propose methods for categorical data analysis based on linked data that are not prepared by the analyst, such that neither the match-key variables nor the unlinked records are available. The adjustment is based on the proportion of false links in the linked file and our approach allows the probabilities of correct linkage to vary across the records without requiring that one is able to estimate this probability for each individual record. It accommodates also the general situation where unmatched records that cannot possibly be correctly linked exist in all the sources. The proposed methods are studied by simulation and applied to real data.

Examining the Aftermath of Virtual Interviewing on Surgical Residency Matches.

INTRODUCTION: Residency interviews have traditionally been conducted in person; however, COVID-19 forced programs to shift to virtual interviewing. This study delineated the nationwide trends observed after virtual interviewing across multiple application cycles on both surgical residency applicant competitiveness and program workload. METHODS: Publicly available National Residency Matching Program applicant and program data were retrospectively reviewed. Applicant competitiveness was assessed using a validated competitive index (# positions ranked/match rate). Interview types included in-person (2010-2020) or virtual (2021-2023), and programs were classified as general surgery (GS), surgical subspecialty (SS) - orthopedics, otolaryngology and neurosurgery, and integrated specialty (IS) - plastic, thoracic, and vascular surgery. RESULTS: When comparing in-person to virtual cohorts, the competitive index has increased in GS (0.97 ± 0.00 to 1.05 ± 0.01, P < 0.001), SS (0.97 ± 0.02 to 1.06 ± 0.01 P < 0.001), and IS (0.93 ± 0.06 to 1.12 ± 0.03, P = 0.001). United Sates Medical Licensing Examination Step scores and research experiences increased over time in GS and SS (P < 0.05). Program workload, represented by number of applications received per program increased in GS, IS, and SS (P < 0.05), as well as the number of interviews conducted in GS and SS (P < 0.05). Importantly, match rate remained stable in GS and IS, with a decrease in SS (0.69 ± 0.03 to 0.63 ± 0.02, P = 0.04). CONCLUSIONS: The residency application process has been irrevocably changed due to COVID-19. The rise in applicant volume and competitiveness places unique strains on applicants and programs. Additional modifications such as signaling and ACGME guidance are needed to help alleviate strain and ensure that residents and programs alike find their best fit.