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Introduction. Mucinous tubular and spindle cell carcinoma of the kidney (MTSCC) is a rare and recently described subtype of renal cell carcinoma (RCC). As its name indicates, the tumor is composed of three morphological structures: tubules consisted of cuboidal cells, spindle cells, and extracellular mucus. Case report. A 59-year-old female patient was admitted to the Emergency Center of the Clinical Center of Vojvodina due to injuries sustained in a traffic accident. After diagnostic procedures, computer tomography (CT) revealed a large asymptomatic cyst of the upper pole of the left kidney as an incidental finding. Four months later, after recovering from traumatic injuries, a control CT confirmed a well-circumscribed tumor, 90 mm in diameter, confined to a kidney, and a radical nephrectomy was performed. Histopathological evaluation showed that the necrotic tumor mass consisted of tubules made of cuboidal cells and cords made of spindle cells separated by pale mucinous material in some areas, while other tumor parts were of dense cellularity without mucin. No atypia was found. Conclusion. MTSCC is a variant of papillary RCC, thus, it is usually mistaken with papillary RCC with sarcomatoid differentiation. Because of the same immunoprofile as papillary RCC, histomorphology is imposed as the gold standard for making the diagnosis. MTSCC is a tumor with a generally favorable prognosis, and complete surgical excision appears to be adequate treatment, but single cases with metastatic disease have been reported. In this case, there were no signs of the dis-ease one year after surgery.

The aim of our study was to examine the scabies incidence in the Croatian population and to analyse potential related factors.

Introduction. Prostate cancer is one of the most common malignancies in men. The most common type is acinar adenocarcinoma. Small cell prostate cancer (SCPC) usually occurs together with coexisting prostate adenocarcinoma. Case report. A 72-years-old patient with voiding simptoms is presented. Initial level of prostate specific antigen (PSA) was 2.87 ng/mL. Twelve prostate biopsies were taken and in six of them neoplastic tissue was detected. The viewed tissue was most convenient to “small cell carcinoma“. Bone scintigraphy did not demonstrate dissemination of the cancer into the skeletal system. Multislice computed tomography (MSCT) of the pelvis did not reveal any special pathological changes. The patient underwent surgery – radical retropubical prostatectomy. Histopathological analysis revealed a poorly differentiated adenocarcinoma of the prostate with small cell carcinoma zones [Gleason score 5+5 (10), grade III, pT3bN1, stage IV]. Conclusion. Poorly differentiated adenocarcinoma of the prostate, especially in combination with SCPC, is an aggressive malignancy with most cases presenting with the extensive disease dissemination on diagnosis and poor prognosis. Small cell carcinomas of the prostate are extremely rare tumors of the neuroendocrine origin. Patients with mixed prostate cancer, compared to pure SCPC, have a better prognosis and greater survival rate. There is a lack of the evidence guiding treatment for SCPC.

OBJECTIVES: To demonstrate the reliability and feasibility of a standardized protocol to assess and score urinary incontinence care in nursing homes. DESIGN: Descriptive. SETTING: Eighteen nursing homes (NHs). PARTICIPANTS: Four hundred twenty-six incontinent residents. MEASUREMENTS: Resident interview data were used to score three quality indicators, and usable data were retrieved from 117 (27%) of 426 incontinent residents in 18 homes who were selected for interview based on evidence that they could accurately describe the care they received. Medical record data were used to score six quality indicators for a subset of 58 participants in five homes. RESULTS: Zero to 98% of the participants were scored as receiving care consistent with the intent of the indicator across the nine indicators. All NHs failed to provide chart documentation of an assessment to determine an incontinent resident's appropriateness for a scheduled toileting program (0% passed). The absence of an assessment to determine a resident's potential responsiveness to toileting assistance may explain why 103 incontinent residents who were documented on the Minimum Data Set as being on a scheduled toileting program reported that they received the same number of toileting assists per day (1.3) as the group of 114 incontinent residents who were not on a scheduled toileting program (1.0). The received toileting assistance frequencies reported by both groups were too low to maintain continence. CONCLUSION: The standardized quality assessment system generated scores for nine incontinence quality indicators with good interrater reliability and provided explicit scoring rules that can facilitate replication. The focus of the indicators on care processes that are under the control of NH staff make the protocol useful for external survey and internal quality improvement purposes. [ABSTRACT FROM AUTHOR]

Introduction. Leiomyosarcoma of the penis (LSP) is an extremely rare form of penile tumor. LSP can be divided into two subtypes: deep and superficial. The goal of this manuscript is to present very rear case of LSP. Case outline. On exam, the patient presented with a slowly “growing penile bump“, for which an initial diagnosis of non-inflamed penile atheroma was given. Further diagnostic workup was omitted. Outpatient excisional biopsy was performed, and the tumor was sent for pathohistological examina-tion (PHE), which revealed LSP. The patient has not received any further treatment. The most recent follow up was 2.5 years after surgery, and the patient continues to do well without any complications. Conclusion. LSP is an extremely rare disease which can be cured if it is diagnosed in its early stage. PHE is necessary for diagnosis of LSP.

Introduction. Urinoma develops after disruption of collecting system of urinary tract and urine leak in surrounding tissue. Most common causes of urinoma are blunt or penetrating trauma. Less common causes are iatrogenic injuries or urinary tract obstruction. In this article we presented a rare case of the urinoma caused by infiltrative bladder cancer. Case report. Acutely ill, a septic patient with ileus and profound azothaemia was admitted to medical intensive care unit. Native computed tomography revealed moderate ileus, right kidney hydronephrosis, extensive retroperitoneal urinoma and vesical thickening with excluded infiltration of ureteral orifices. Computed tomography guided percutaneous drainage was done. Upon stabilization, patient underwent transurethral bladder tumor electroresection (histopathology report was: infiltrative transitional cell tumor of urinary bladder). Radical cystectomy was done. The patient’s recovery was uneventful. Conclusion. Urinoma formed due to spontaneous rupture of collecting system based on ureteral obstruction caused by urinary bladder tumor is very rare clinical case scenario. In case of urinoma of unclear etiology invasive bladder cancer should be excluded.

The paper is considering the stability condition of equilibrium position of a beam undergoing large displacements due to a conservative force. Numerical example is presented.

The paper looks at some aspects of the Thracian Hero cult on the Danube frontier of Upper Moesia inspired by a reinterpretation of a Latin votive inscription from Diana, which, as the paper proposes, was dedicated to Deo Totovitioni. Based on epigraphic analogies, the paper puts forth the view that it was a dedication to the Thracian Hero, since it is in the context of this particular cult that the epithet Totovitio has been attested in various variants (Toto-viti- / Toto-bisi- / Toto-ithi-).

Introduction. In males the ectopic ureter usualy drains into the prostate (50%). During ureteric developement a thin membrane (Chawalla’s membrane) separates the lumen of the ureter and the urogenital sinus at the point where the ureter joins the urogenital sinus. This membrane ruptures allowing urin to drain from the ureter to the urogenital sinus. The authors reported a case of renal dysplasia associated with ipsilateral uretral ectopia mimicking prostatic abscess. Case report. A subfebrile (37.3°C), 23-year-old patient, otherwise healthy, presented with persistent ascending perineal pain non-responsive to antibiotics and analgetics. Digitorectal examination (DRE) showed asymmetric prostate with a soft, tender, buldging left lobe suggestive of prostatic abscess. The diagnosis was suspected using transrectal ultrasonography (TRUS), but the picture of the anechoic tubular structure in the left lobe of the prostate with a proximal undefined extraprostatic extension and a caudal intraprostatic blind end was incoclusive for the definitive diagnosis of prostatic abscess. Magnetic resonance imaging (MRI) was ordered and definitive diagnosis of renal dysplasia associated with the ipsilateral ectopic ureter filled with inflamed content mimicking prostatic abscess was made. Transurethral incision/minimal resection of the distal, blindly closed end of left ectopic ureter was done. Endoscopic surgical treatment was sufficient for relief of clinical symptoms. The patient’s recovery was uneventful. Conclusion. To the best of our knowledge, a case of renal dysplasia with the ipsilateral ectopic ureter mimicking prostate abscess has not been reported so far. Cystic pelvic malformations in males may result from too craniall sprouting of the ureteral bud, with delayed absorption and ectopic opening of the distal end of the ureter.

A new votive inscription from the territory of Doclea has recently been published. The reading of the text needs revision, and consequently, reinterpretation. The inscription should be read as follows: Neptuno ׀ sacrum p׀ericuloru׀m Absolu׀tori Petro׀5nius Aspe׀r v(otum) s(olvit) ׀ l(ibens) a(nimo). Neptune’s attribute periculorum Absolutor appears here for the first time. The noun «Absolutor», i.e. «he who absolves, liberator », attested late in the narrative sources e.g. Cassiod. Var . XI, praef. 3, should be close to the Jupiter’s epithets Liberator or Servator. The dedication could be connected with a successful ending of a journey, possibly after being exposed to maritime perils: the dedicator may well be a person engaged in trade and businesses that involve transmarine voyage. His name - Petronius Asper - implies the connection with the large group of Italian settlers in Dalmatia, whose presence is attested in the province all through the Principate. Such relations are illustrated in the light of other Dalmatian examples.

The lamp stamped Cilices, dating from the Severan epoch and found at Singidunum (Moesia Superior) but overlooked by modern scholars, offers interesting additional evidence on the Cilices contirones, attested by the contemporary altar IMS I, 3. Almost certainly, the two inscriptions refer to the same legionaries, the men of IIII Flavia, grouped professionally (serving as the legion's sailors?) as well as ethnically. The circumstances and the date of the recruitment of the contirones have been studied by H. Nesselhauf and, from another perspective, M.P. Speidel; the inscription of the lamp tends to sustain Professor Speidel's points of view. The archaeological context of the lamp implies its provenance from a military building where the Cilices may have had their club, and/or their sacellum. Similar ethnic clubs and their buildings are well known from military and other inscriptions. For an instructive (but neglected) Upper Moesian parallel see IMS VI, 187 ([Ch]airete, Gal‌‌‌│atai); cf. the Galatian Aur. Asclepiades' conveterani from leg. IIII Flavia (Speidel 1984, 50, no° 28).

Objective. The objective of this study was to investigate the impact of extreme maternal BMI on pregnancy outcomes and the costs of perinatal care at tertiary level hospital in Serbia. Methods. We performed a retrospective study of the cohort of pregnant women registered during the first trimester screening in the period from March 2016 to February 2017 and had delivery in Gynaecology and Obstetrics Clinic "Narodni front"; in Belgrade, Serbia. We evaluated 3 who were extremely obese (BMI ≥ 3 kg/m2). Multiple pregnancies were excluded. Data collection about their prepregnancy and perinatal morbidity, pregnancy outcomes and costs of the healthcare we gain using their EHR and electronic hospital bills. Comparisons were made with other pregnant women who had delivery in the observing period. Results. Additional prepregnancy comorbidity was present in the 20.6% of extremely obese patients. Their pregnancy was mostly complicated with gestational diabetes (33.3%) and hypertension (27%). 52.4% pregnancy ended by SC and 47.6% vaginaly out of which 7.9% were preterm. In comparison with other patients OR for delivery complications was 1.45 CI 95% (0.85- 2.47) and OR for SC was 2.31 CI 95% (1.41-3.80). Average length of hospital stay during whole period of pregnancy was 9 days for vaginaly ended pregnancy and 13 for SC respectively. The total costs for the perinatal healthcare of extremely obese pregnant patient were 52.8% above the average after SC and 47% after vaginal delivery in tertiary level hospital. Conclusions. Extremely obese pregnancy becomes entity which demands special clinical attention and resources. Maternal obesity could have a longer-term implications for the mother and infant health and therefore prevention and treatment of obesity may reduce meaningful health consequences and future economic costs. [ABSTRACT FROM AUTHOR]

Purpose: This study describes graduate medical education (GME) placement outcomes for recent U.S. medical school graduates and examines racial and ethnic differences in GME placement among these graduates., Method: This retrospective, observational study used data collected from and about U.S. medical school graduates for academic years 2015-2016 through 2021-2022. An individual-level, deidentified database was constructed to examine GME placement at graduation in association with race and ethnicity, as well as other demographic and academic and professional development variables. Multilevel (nested by school) logistic regression models identified variables independently associated with GME placement at graduation, reporting unadjusted odds ratios (UORs) and adjusted odds ratios (AORs) with 95% CIs., Results: The study sample included 140,072 of 140,073 eligible graduates (> 99.9%; 1 graduate missing gender information was excluded), of whom 136,022 (97.1%) were placed in GME at graduation. Proportions of graduates placed in GME varied by race and ethnicity and by each covariable examined. In addition, proportions of graduates placed in GME varied by school (N = 152; mean [SD], 96.9% [3.4%]; P < .001). In multilevel (nested by school) models, GME placement UORs were lower for (among other groups examined) Asian (UOR, 0.76; 95% CI, 0.70-0.83), Black or African American (UOR, 0.44; 95% CI, 0.39-0.49), and Hispanic (UOR, 0.70; 95% CI, 0.60-0.80) graduates (vs White). The GME placement AORs, adjusted for all covariables, were similar for Asian (AOR, 0.96; 95% CI, 0.87-1.07), Black or African American (AOR, 0.89; 95% CI, 0.77-1.02), and Hispanic (AOR, 1.06; 95% CI, 0.89-1.25) graduates (vs White)., Conclusions: The proportion of graduates placed in GME at graduation during the 7 years of the study was high. However, there were racial and ethnic differences in this outcome during the study period., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Association of American Medical Colleges.)

Aim: Explore the safety of Belbuca® (buprenorphine buccal film), buprenorphine transdermal patches and oral opioids for chronic low back pain (cLBP) treatment. Methods: The retrospective analysis of the MarketScan Commercial database (2018-2021) included treatment-naive cLBP adults. The first date of buprenorphine (Belbuca and transdermal patch) or opioid prescription was index date. Cohorts were defined based on the index medication. Observation included a 6-month pre-index period, while post-index lasted until the end of continuous insurance coverage. There were 44 relevant treatment-emergent adverse events (TEAEs) identified in the literature. Incidence rate ratio (IRR) and incidence rate difference (IRD) were used to compare serious TEAE rates (in 1000 person-years) between cohorts. Propensity-score matching minimized the selection bias. Results: Buprenorphine had lower rates of 15 serious TEAEs than oral opioids (all p ≤ 0.037), while higher rates only for serious dizziness (IRR 2.44, p = 0.011; driven by Belbuca), opioid abuse/dependence (IRR 3.13, p = 0.004; driven by patches) and cholecystitis (IRD 20.25, p = 0.044; an outlier). Additionally, a comparison between Belbuca and oral opioids showed lower rates of 13 serious TEAEs (all p ≤ 0.024) and a higher serious dizziness rate (IRR 3.17, p = 0.024). Although the rates of serious opioid abuse/dependence were similar (24.60 vs 26.93, p = 0.921), all Belbuca patients and none of the opioid patients had a positive history of these events. Belbuca also had lower rates of five serious TEAEs than transdermal patches (all p ≤ 0.018), including a serious opioid abuse/dependence (IRR 0.04, p < 0.001), but higher rates of serious cholecystitis (IRD 52.17, p = 0.035; an outlier) and suicidal ideation (IRD 156.50, p < 0.001; an outlier). Conclusion: Buprenorphine had a better safety profile than oral opioids in cLBP treatment. Belbuca showed a more favorable TEAE profile than buprenorphine transdermal patches and oral opioids.

Background & Aims: Treatment outcomes for people living with autoimmune hepatitis (AIH) are limited by a lack of specific therapies, as well as limited well-validated prognostic tools and clinical trial endpoints. We sought to identify predictors of outcome for people living with AIH., Methods: We evaluated the clinical course of people with AIH across 11 Canadian centres. Biochemical changes were analysed using linear mixed-effect and logistic regression. Clinical outcome was dynamically modelled using time-varying Cox proportional hazard modelling and landmark analysis., Results: In 691 patients (median age 49 years, 75.4% female), with a median follow-up of 6 years (25th-75th percentile, 2.5-11), 118 clinical events occurred. Alanine aminotransferase (ALT) normalisation occurred in 63.8% of the cohort by 12 months. Older age at diagnosis (odd ratio [OR] 1.19, 95% CI 1.06-1.35) and female sex (OR 1.94, 95% CI 1.18-3.19) were associated with ALT normalisation at 6 months, whilst baseline cirrhosis status was associated with reduced chance of normalisation at 12 months (OR 0.52, 95% CI 0.33-0.82). Baseline total bilirubin, aminotransferases, and IgG values, as well as initial prednisone dose, did not predict average ALT reduction. At baseline, older age (hazard ratio [HR] 1.25, 95% CI 1.12-1.40), cirrhosis at diagnosis (HR 3.67, 95% CI 2.48-5.43), and elevated baseline total bilirubin (HR 1.36, 95% CI 1.17-1.58) increased the risk of clinical events. Prolonged elevations in ALT (HR 1.07, 95% CI 1.00-1.13) and aspartate aminotransferase (HR 1.13, 95% CI 1.06-1.21), but not IgG (HR 1.01, 95% CI 0.95-1.07), were associated with higher risk of clinical events. Higher ALT at 6 months was associated with worse clinical event-free survival., Conclusion: In people living with AIH, sustained elevated aminotransferase values, but not IgG, are associated with poorer long-term outcomes. Biochemical response and long-term survival are not associated with starting prednisone dose., Impact and Implications: Using clinical data from multiple Canadian liver clinics treating autoimmune hepatitis (AIH), we evaluate treatment response and clinical outcomes. For the first time, we apply mixed-effect and time-varying survival statistical methods to rigorously examine treatment response and the impact of fluctuating liver biochemistry on clinical event-free survival. Key to the study impact, our data is 'real-world', represents a diverse population across Canada, and uses continuous measurements over follow-up. Our results challenge the role of IgG as a marker of treatment response and if normalisation of IgG should remain an important part of the definition of biochemical remission. Our analysis further highlights that baseline markers of disease severity may not prognosticate early treatment response. Additionally, the initial prednisone dose may be less relevant for achieving aminotransferase normalisation. This is important for patients and treating clinicians given the relevance and importance of side effects., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: The COVID-19 pandemic resulted in unprecedented changes to the medical education learning environment. The graduating class of 2021 was particularly affected. To better understand how students were affected, the authors explored positive and negative experiences described by graduating U.S. medical students., Method: Using the conceptual framework of affordances, the authors examined narrative responses to 2 new open-ended questions on the Association of American Medical Colleges 2021 Graduation Questionnaire in which graduating students described the pandemic's positive and negative effects on their medical school experiences and career preparation. Conventional content analysis was used to identify affordances and themes in responses., Results: Of 16,611 Graduation Questionnaire respondents, 8,926 (54%) provided narrative responses. Of these 8,926 respondents, responses from 2,408 students (27%) were analyzed. Students described positive and negative perceptions of affordances, centering around virtual learning, social connection, and transition to residency. Fewer in-person and increased virtual clinical rotations offered students flexible scheduling, allowing them greater opportunity to explore academic and professional interests. Additionally, students' sense of isolation from their medical school was alleviated when schools exercised intentional open communication and student involvement in decision making. Although many described a diminished sense of preparedness for residency due to limited access to in-person clinical experiences and to assessing residencies largely through virtual away rotations and interviews, the sense of community, adaptability, and resiliency gained through varied activities reinforced students' professional identity and commitment to medicine during a time of much uncertainty., Conclusions: This national exploration of students' pandemic experiences highlights what students value as fundamental elements of medical education and student support and describes how innovation can improve long-standing practices. These findings, guided by students' insights, can help inform the work of educational leaders as they consider which innovations should remain to continue enhancing student learning, engagement, and well-being., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Association of American Medical Colleges.)

Objective: To determine the extent to which U.S. Liaison Committee of Medical Education (LCME)-accredited medical schools chose to participate in piloting a national curricular resource, the American College of Surgeons/Association of Program Directors in Surgery/Association of Surgical Education Resident Prep Curriculum ("ACS-surgery-prep curriculum"), and implications of such participation for student access nationally to this resource., Design: We examined the significance of school-level differences in ACS-surgery-prep curriculum pilot participation and student-level differences in curriculum access based on medical school attended in bivariate analysis., Setting: U.S. medical schools choosing to participate in the ACS-surgery-prep curriculum through 2021. Students graduating from U.S. LCME-accredited medical schools in 2020-2021 were invited to complete the Association of American Medical Colleges 2021 Graduation Questionnaire (GQ)., Participants: Our study included data for 2569 students intending surgery specialties (16% of 16,353 2021 GQ respondents) from ACS-surgery-prep curriculum pilot and non-pilot schools., Results: Of 148 medical schools attended by 2021 GQ respondents, 93 (63%) were identified as ACS-surgery-prep curriculum pilot schools. Pilot participation varied by school region, community-based designation, and research intensity (each p < 0.05) but not by ownership or transition to residency (TTR) course requirements (each p > 0.05). Of 2569 GQ respondents nationally intending surgery specialties, 1697 (66%) attended an ACS-surgery-prep curriculum pilot school; this proportion did not vary by gender or race/ethnicity (each p > 0.05) but varied by students' school TTR course requirements (p < 0.001). Findings were similar among the 1059 students intending general surgery specialties specifically (41% of all 2569 students intending surgery specialties)., Conclusions: Many U.S. LCME-accredited medical schools piloted this national TTR surgery curriculum. School-level characteristics associated with pilot participation can inform outreach efforts to encourage the participation of interested schools in piloting this TTR resource. With this curriculum distribution model, we observed no gender or racial/ethnic disparities in curriculum access nationally among students intending surgery specialties., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: Retrospective insurance claims analysis exploring treatment characteristics in chronic low back pain patients prescribed buprenorphine buccal film (Belbuca ® ) or transdermal patches. Patients and methods: The first buprenorphine prescription (buccal film or transdermal patch) was an index event. Patients were observed over 6 month pre- and post-index periods. Propensity score matching minimized the selection bias. Results: Buccal film patients had a higher buprenorphine daily dose (501.7 vs 270.9 µg; p < 0.001). The patch-to-film switching rate was higher than vice versa (11.5 vs 3.8%; p < 0.001). The buccal film showed a greater reduction in opioid prescriptions (-1.1 vs -0.7; p = 0.012), daily morphine milligram equivalents (-12.6 vs -7.3; p < 0.001) and opioid treatment duration (-13.4 vs -7.6 days; p = 0.022). Conclusion: Buccal film was associated with higher buprenorphine doses and a greater reduction of opioid burden.

Aim: Exploring prescribing trends and economic burden of chronic low back pain (cLBP) patients prescribed buprenorphine buccal film (Belbuca®) or transdermal patches. Methods: In the MarketScan® commercial insurance claims (employees and their spouses/dependents, 2018-2021), the first film or patch prescription date was an index event. The observation covered 6-month pre-index and 12-month post-index periods. Results: Patients were propensity-score matched (708 per cohort). Buprenorphine initiation had stable cost trends in buccal film and increasing trends in transdermal patch cohort. Between-cohort comparisons of healthcare expenditures, cost trends and resource utilization showed significant differences, mostly in favor of buccal film. Buccal film also had higher daily doses and wider dosing range. Conclusion: Buprenorphine film is more cost-effective cLBP treatment with more flexible dosing.

Background: COVID-19 severity is associated with its respiratory manifestations. Neutralising antibodies against SARS-CoV-2 administered systemically have shown clinical efficacy. However, immediate and direct delivery of neutralising antibodies via inhalation might provide additional respiratory clinical benefits. IBIO123 is a cocktail of three, fully human, neutralising monoclonal antibodies against SARS-CoV-2. We aimed to assess the safety and efficacy of inhaled IBIO123 in individuals with mild-to-moderate COVID-19., Methods: This double-blind, dose-ascending, placebo-controlled, first-in-human, phase 1/2 trial recruited symptomatic and non-hospitalised participants with COVID-19 in South Africa and Brazil across 11 centres. Eligible participants were adult outpatients (aged ≥18 years; men and non-pregnant women) infected with COVID-19 (first PCR-confirmed within 72 h) and with mild-to-moderate symptoms, the onset of which had to be within 10 days of randomisation. Using permuted blocks of four, stratified by site, we randomly assigned participants (1:3) to receive single-dose placebo or IBIO123 (1 mg, 5 mg, or 10 mg) in phase 1, and single-dose placebo or IBIO123 (10 mg) in phase 2, in addition to local standard of care. Participants underwent serological testing to identify antibodies against SARS-CoV-2. Participants, investigators, and the study team were masked to treatment assignment. In phase 1, the primary outcome was the safety assessment in the safety population (ie, all participants who received an intervention). In phase 2, the primary outcome was the mean absolute change from baseline to day 5 in SARS-CoV-2 viral load measured by nasopharyngeal swabs analysed using a mixed model for repeated measures in the full analysis set (FAS; ie, participants with one analysable viral load value at baseline and at least one analysable viral load value at day 3 or day 5). Secondary clinical outcomes included safety from baseline to day 29, assessed by evaluating adverse events; the effect of IBIO123 on baseline COVID-19 symptoms resolution until day 6, with symptoms systemically evaluated by the investigators; and disease progression as measured by the COVID-19 WHO Clinical Progression Scale. For clinical endpoints in phase 2, we used a modified FAS (ie, participants who had at least one analysable viral load value over the course of the study, confirming that they were infected with SARS-CoV-2). This trial is now completed and is registered with ClinicalTrials.gov, NCT05298813., Findings: Between Dec 4, 2021, and May 23, 2022, 24 participants were enrolled in phase 1. Between July 20, 2022, and Jan 4, 2023, 138 participants were enrolled in phase 2 and five were excluded because they did not meet the inclusion criteria. Participants were randomly assigned to receive IBIO123 (n=18) or placebo (n=6) in phase 1, and randomly assigned to receive IBIO123 (n=104) or placebo (n=34) in phase 2. In phase 2, the study was stopped before reaching the planned accrual because of a decline in COVID-19 incidence. In phase 1, no safety issues were observed. In phase 2, the difference in mean absolute change from baseline viral load to day 5 between participants in the IBIO123 group and participants in the placebo group was -0·29 log 10 copies per mL (95% CI -1·32 to 0·75; p=0·45) in the FAS population and -0·49 log 10 copies per mL (-1·56 to 0·58; p=0·20) in seropositive participants. In the modified FAS, 81 (69%) of 118 participants were at high risk of severe disease progression. The number of participants with resolution of respiratory symptoms at day 6 was 34 (42%) of 81 in the IBIO123 group versus five (17%) of 29 in the placebo group (p=0·017) in the modified FAS population and 19 (35%) of 55 versus three (14%) of 21 among participants at high risk (p=0·083). One participant died and one participant was hospitalised in the placebo group, whereas no deaths or hospitalisations were reported in the IBIO123 group. 39 (38%) of 104 participants in the IBIO123 group had adverse events, compared with 13 (38%) of 34 in the placebo group., Interpretation: Inhalation of IBIO123 was safe. Despite the lack of significant reduction of viral load at day 5, treatment with IBIO123 resulted in a higher proportion of participants with complete resolution of respiratory symptoms at day 6. This study supports further clinical research on inhaled monoclonal antibodies in COVID-19 and respiratory diseases in general., Funding: Canadian Strategic Innovation Fund and Immune Biosolutions., Competing Interests: Declaration of interests BM, SML, ML, PB, AlF, J-FL, DG, AL, FL, and SG are all employees of Immune Biosolutions. AnF holds patents on mAbs contained in IBIO123 (WO CA2021/051873 and WO CA2022/051074). YS declares no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: One-third of medical school applicants attend a community college (CC), and they represent a diverse group of applicants. However, they have a lower likelihood of being accepted to medical school. Using application-level data, this study examines how an applicant's CC attendance impacts the likelihood of application acceptance and how 3 medical school characteristics moderate this association., Method: Data examined were from 2,179,483 applications submitted to at least one of 146 U.S. Liaison Committee on Medical Education-accredited medical schools by 124,862 applicants between 2018 and 2020. The outcome was application acceptance. The main measures were applicants' CC attendance (no, lower [> 0%-19% of college course hours], or higher [≥ 20%]) and 3 medical school characteristics: geographic region, private versus public control, and admissions policy regarding CC coursework. Multilevel logistic regression models estimated the association between CC attendance and the likelihood of application acceptance and how this association was moderated by school characteristics., Results: Among applicants, 23.8% (29,704/124,862) had lower CC attendance and 10.3% (12,819/124,862) had higher CC attendance. Regression results showed that, relative to no CC attendance, applications with lower (adjusted odds ratio [AOR] = .96; 95% confidence internal [CI], .94-.97) and higher (AOR = .78; 95% CI, .76-.81) CC attendance had significantly decreased odds of acceptance when the 3 school characteristics were included. Each of the 3 medical school characteristics significantly moderated the association between an applicant's CC attendance and the likelihood of application acceptance., Conclusions: The negative association between CC attendance and medical school application acceptance varies by medical school characteristics. Professional development for admissions officers focused on understanding the CC pathway and potential biases related to CC attendance would likely be beneficial in terms of trying to attract and select a diverse cohort of medical students in a holistic and equitable manner., (Copyright © 2023 by the Association of American Medical Colleges.)

Background The process for program directors (PDs) to provide feedback to medical schools about their graduates' readiness for postgraduate year 1 (PGY-1) training is burdensome and does not generate national benchmarking data. Objective The Association of American Medical Colleges (AAMC) tested the feasibility of administering a standardized Resident Readiness Survey (RRS) to PDs nationally about their PGY-1 residents' preparedness for residency. Methods In 2020 and 2021, the AAMC invited PDs via email to complete RRSs for their PGY-1s who graduated from participating schools; the AAMC provided schools with reports of identified RRS data for their graduates. Outcome measures included school participation rates, PD response rates, PGY-1s' coverage rates (RRSs completed/RRSs PDs invited to complete), RRS completion time (time-stamp difference: RRS opening-submission), and participating schools' feedback about the process collected via AAMC evaluation questionnaires sent to school leaders. Chi-square tested significance of differences between proportions. Results School participation increased from 43.8% (2020: 77 of 176) to 72.4% (2021: 131 of 181). PD response rates, similar in both years overall (2020: 1786 of 2847 [62.7%]; 2021: 2107 of 3406 [61.9%]; P =.48), varied by specialty ( P <.001; range 65 of 154 [42.2%], neurology; 109 of 136 [80.1%], internal medicine-pediatrics, both years combined). PGY-1s' coverage rates were similar ( P =.21) in 2020 (5567 of 10 712 [52.0%]) and 2021 (9688 of 18 372 [52.7%]). RRS completion time averaged less than 3 minutes. Numerous school leaders reported that RRS data stimulated new, or supported ongoing, curricular quality improvement. Conclusions Administration of a standardized RRS to PDs nationally about PGY-1s preparedness for residency is feasible and will continue.

Background: Simulating DNA evolution has been done through coevolution-agnostic probabilistic frameworks for the past 3 decades. The most common implementation is by using the converse of the probabilistic approach used to infer phylogenies which, in the simplest form, simulates a single sequence at a time. However, biological systems are multi-genic, and gene products can affect each other's evolutionary paths through coevolution. These crucial evolutionary dynamics still remain to be simulated, and we believe that modelling them can lead to profound insights for comparative genomics., Results: Here we present CastNet, a genome evolution simulator that assumes each genome is a collection of genes with constantly evolving regulatory interactions in between them. The regulatory interactions produce a phenotype in the form of gene expression profiles, upon which fitness is calculated. A genetic algorithm is then used to evolve a population of such entities through a user-defined phylogeny. Importantly, the regulatory mutations are a response to sequence mutations, thus making a 1-1 relationship between the rate of evolution of sequences and of regulatory parameters. This is, to our knowledge, the first time the evolution of sequences and regulation have been explicitly linked in a simulation, despite there being a multitude of sequence evolution simulators, and a handful of models to simulate Gene Regulatory Network (GRN) evolution. In our test runs, we see a coevolutionary signal among genes that are active in the GRN, and neutral evolution in genes that are not included in the network, showing that selective pressures imposed on the regulatory output of the genes are reflected in their sequences., Conclusion: We believe that CastNet represents a substantial step for developing new tools to study genome evolution, and more broadly, coevolutionary webs and complex evolving systems. This simulator also provides a new framework to study molecular evolution where sequence coevolution has a leading role., (© 2023. The Author(s).)