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Duvelisib, an oral dual inhibitor of PI3K-δ and PI3K-γ, is in phase III trials for the treatment of chronic lymphocytic leukemia (CLL) and indolent non-Hodgkin's lymphoma. In CLL, duvelisib monotherapy is associated with high iwCLL (International Workshop on Chronic Lymphocytic Leukemia) and nodal response rates, but complete remissions are rare. To characterize the molecular effect of duvelisib, we obtained samples from CLL patients on the duvelisib phase I trial. Gene expression studies (RNAseq, Nanostring, Affymetrix array and real-time RT-PCR) demonstrated increased expression of BCL2 along with several BH3-only pro-apoptotic genes. In concert with induction of transcript levels, reverse phase protein arrays and immunoblots confirmed increase at the protein level. The BCL2 inhibitor venetoclax induced greater apoptosis in ex vivo-cultured CLL cells obtained from patients on duvelisib compared with pre-treatment CLL cells from the same patients. In vitro combination of duvelisib and venetoclax resulted in enhanced apoptosis even in CLL cells cultured under conditions that simulate the tumor microenvironment. These data provide a mechanistic rationale for testing the combination of duvelisib and venetoclax in the clinic. Such combination regimen (NCT02640833) is being evaluated for patients with B-cell malignancies including CLL.

The article discusses a study to evaluate the safety of training and assessment in operating theaters by assessing the performance of specialists and trainees. The findings revealed that no significant differences were observed between the procedural outcomes of trainees and specialists, thereby indicating that trainees are safe to operate under senior supervision. Several procedural outcomes have been found capable of evaluating the performance of clinicians and healthcare systems.

Objectives Healthcare research performance is increasingly assessed through research indicators. We performed a systematic review to identify the indicators that have been used to measure healthcare research performance. We evaluated their feasibility, validity, reliability and acceptability; and finally assessed the utility of these indicators in terms of measuring performance in individuals, specialties, institutions and countries. Design A systematic review was performed by searching EMBASE, PsycINFO, Ovid MEDLINE and Cochrane Library databases between 1950 and September 2010. Setting Studies of healthcare research were appraised. Healthcare was defined as the prevention, treatment and management of illness and the preservation of mental and physical wellbeing through the services offered by the medical and allied health professions. Participants All original studies that evaluated research performance indicators in healthcare were included. Main outcome measures Healthcare research indicators, data sources, study characteristics, results and limitations for each study were studied. Results The most common research performance indicators identified in 50 studies were: number of publications (n = 38), number of citations (n = 27), Impact Factor (n = 15), research funding (n = 10), degree of co-authorship (n = 9), and h index (n = 5). There was limited investigation of feasibility, validity, reliability and acceptability, although the utility of these indicators was adequately described. Conclusion Currently, there is only limited evidence to assess the value of healthcare research performance indicators. Further studies are required to define the application of these indicators through a balanced approach for quality and innovation. The ultimate aim of utilizing healthcare research indicators is to create a culture of measuring research performance to support the translation of research into greater societal and economic impact. [ABSTRACT FROM AUTHOR]

BACKGROUND: A knowledge and understanding of specialist anatomy, which includes radiological, laparoscopic, endoscopic and endovascular anatomy is essential for interpretation of imaging and development of procedural skills. METHODS AND MATERIALS: Medical students, specialist trainees and specialists from the London (England, UK) area were surveyed to investigate individual experiences and recommendations for: (1) timing of the introduction of specialist anatomy teaching, and (2) pedagogical methods used. Opinions relating to radiological, laparoscopic, endoscopic and endovascular anatomy were collected. Non-parametric tests were used to investigate differences in recommendations between specialist trainees and specialists. RESULTS: Two hundred and twenty-eight (53%) individuals responded to the survey. Imaging was most commonly used to learn radiological anatomy (94.5%). Procedural observation was most commonly used to learn laparoscopic (89.0%), endoscopic (87.3%) and endovascular anatomy (66.2%). Imaging was the most recommended method to learn radiological anatomy (92.1%). Procedural observation was the most recommended method for learning laparoscopic (80.0%), endoscopic (81.2%) and endovascular anatomy (42.5%). Specialist trainees and specialists recommended introduction of specialist anatomy during undergraduate training. CONCLUSION: Although the methods for specialist anatomy learning are in practice, there is no consensus on timing and structure within the anatomy curriculum. Recommendations from trainees and specialists should be considered so that the existing curriculum can be refined to maximise learning outcomes. [ABSTRACT FROM AUTHOR]

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare type of non-Hodgkin lymphoma characterized by subcutaneous nodules, indurated plaques, erythema, and cellular infiltrates in the subcutaneous fat. Biopsies show neoplastic cells expressing cytotoxic T-cell markers and displaying moderate cytologic atypia while sparing the dermis and epidermis and showing variable degrees of necrosis, hemorrhage, and inflammatory changes. We describe a pediatric case of SPTCL in a 6-year-old boy, presenting with an unusual targetoid plaque and systemic symptoms, who showed significant improvement on systemic immunosuppressants without chemotherapy. This case underscores the potential for atypical presentations of SPTCL and the efficacy of immunosuppressive therapy in achieving favorable clinical outcomes, adding to the understanding of SPTCL's clinical diversity and treatment strategies., (© 2025 Wiley Periodicals LLC.)

Study Design: Retrospective Study., Objective: Myxopapillary ependymomas (MPEs) are a unique subgroup of spinal ependymomas originating from the filum terminale's ependymal glia. The 2021 WHO classification reclassified all MPEs as grade 2, recognizing their higher recurrence risk. Due to their rarity, our objective with this study is to understand MPEs' clinical course and optimal management through a large retrospective cohort analysis., Methods: From the years 2000 to 2020, patients with MPEs were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariable Cox proportional hazard models were run to identify variables that had a significant impact on the primary endpoint of overall survival (OS). A predictive nomogram was built to predict 5-year and 10-year survival probability., Results: This retrospective cohort includes 1373 patients. Patients 65 years or older at diagnosis had a poorer OS ( P < 0.001). Most patients received subtotal resection. Only 320 patients (23%) received gross total resection (GTR). Patients that received GTR had the best OS when compared against all other modalities of treatment ( P < 0.05). Receiving radiotherapy did not affect OS in patients with MPE ( P = 0.2). Nomogram includes patient age and treatment modalities, demonstrating acceptable accuracy in estimating the survival probability at 5-year and 10-year intervals, with a C-index of 0.80 (95% CI of 0.71 to 0.90)., Conclusion: This study highlights the survival benefit of GTR in the treatment of patients with MPE. The role of adjuvant radiotherapy remains unclear as it did not seem to improve OS. The nomogram stratifies the risk of survival in patients with MPE based on age and treatment modality., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

BACKGROUND Encapsulating peritoneal sclerosis (EPS) is a life-threatening complication of peritoneal dialysis (PD). It is characterized by a fibrous membrane partially or totally encasing the small bowel and is a rare cause of small bowel obstruction (SBO). Here we present a case of a young woman with a history of PD presenting with SBO due to EPS. CASE REPORT A 37-year-old woman with end-stage renal disease secondary to uncontrolled hypertension previously on PD presented to the emergency department for evaluation of 1 week of intractable nausea and vomiting associated with diffuse abdominal pain. Computed tomography of the abdomen showed findings consistent with a fibrous membrane encapsulating the small bowel and a small bowel follow-through revealed an SBO. She was diagnosed with secondary stage 3 EPS due to PD. She was started on prednisone and tamoxifen with quick resolution of her symptoms. Unfortunately, due to numerous recurrent SBOs, she is now being evaluated for surgical treatment options. CONCLUSIONS This report has presented a case of EPS, a rare complication of PD, which requires early diagnosis and management to prevent potentially fatal consequences. Management should focus on treating the underlying condition, optimizing nutrition, and using corticosteroids or tamoxifen (alone or in combination) depending on disease state and contraindications, with the aim of reducing recurrent SBOs. Failure of conservative management may require surgical evaluation.

As the indications for endoscopic skull base approaches have increased, so has the need for more versatile vascularized flaps for skull base reconstruction. Here, we describe a novel lateral based nasopharyngeal flap (LNPF). Two cadaver heads were dissected to elucidate flap anatomy, dimensions, and technique. A retrospective review was performed on two cases where LNPF was used to repair CSF leaks in the nasopharyngeal area, and outcomes reported. The LNPF is an ascending pharyngeal artery myomucosal flap that includes the nasopharyngeal mucosa and the superior pharyngeal constrictor muscle. The flap was 1.2 × 2.2 cm in greatest dimensions. The LNPF was used for salvage CSF leak repair in two cases: one clival and one tubal. Both patients had resolution of leak at 7 months follow-up. The LNPF is a novel flap with reconstruction potential for the nasopharynx, including the lower clivus and the eustachian tube., (© 2024 Wiley Periodicals LLC.)

Brain metastases are an uncommon yet life-limiting manifestation of prostate cancer. However, there is limited insight into the natural progression, therapeutics, and patient outcomes for prostate cancer once metastasized to the brain. This is a retrospective study of 461 patients with metastatic prostate cancer to the brain with a primary outcome of median overall survival (OS). The Surveillance, Epidemiology, and End Results (SEER) database was examined using Cox regression univariate and multivariable analyses, and a corresponding nomogram was developed. The median overall survival was 15 months. In the multivariable analysis, Hispanic patients had significantly increased OS (median OS 17 months, p = 0.005). Patients with tumor sizes greater than three centimeters exhibited significantly reduced OS (median OS 19 months, p = 0.014). Patients with additional metastases to the liver exhibited significantly reduced OS (median OS 3.5 months, p < 0.001). Increased survival was demonstrated in patients treated with chemotherapy or systemic treatment (median OS 19 months, p = 0.039), in addition to radiation and chemotherapy (median OS 25 months, p = 0.002). The nomogram had a C-index of 0.641. For patients with prostate metastases to the brain, median OS is influenced by race, tumor size, presence of additional metastases, and treatment. The lack of an association between traditional prostate cancer prognosis metrics, including Gleason and ISUP grading, and mortality highlights the need for individualized, metastasis-specific prognosis metrics. This prognostic nomogram for prostate metastases to the brain can be used to guide the management of affected patients.

Purpose: The open-label, phase III EVOKE-01 study evaluated sacituzumab govitecan (SG) versus standard-of-care docetaxel in metastatic non-small cell lung cancer (mNSCLC) with progression on/after platinum-based chemotherapy, anti-PD-(L)1, and targeted treatment for actionable genomic alterations (AGAs). Primary analysis is reported., Methods: Patients were randomly assigned 1:1 (stratified by histology, best response to last anti-PD-(L)1-containing regimen, and AGA treatment received or not) to SG (one 10 mg/kg intravenous infusion on days 1 and 8) or docetaxel (one 75 mg/m 2 intravenous infusion on day 1) in 21-day cycles. Primary end point was overall survival (OS). Key secondary end points were investigator-assessed progression-free survival (PFS), objective response rate, patient-reported symptom assessment, and safety., Results: In the intention-to-treat population (SG, n = 299; docetaxel, n = 304), 55.4% had one previous line of therapy. Median follow-up was 12.7 months (range, 6.0-24.0). The primary end point was not met. There was a numerical OS improvement for SG versus docetaxel (median, 11.1 v 9.8 months; hazard ratio [HR], 0.84 [95% CI, 0.68 to 1.04]; one-sided P = .0534), consistent across squamous and nonsquamous histologies. Median PFS was 4.1 versus 3.9 months (HR, 0.92 [95% CI, 0.77 to 1.11]). An OS benefit was observed for SG (n = 192) versus docetaxel (n = 191) in mNSCLC nonresponsive to last anti-PD-(L)1-containing regimen (3.5-month median OS increase; HR, 0.75 [95% CI, 0.58 to 0.97]); this was consistent across histologies. Among patients receiving SG and docetaxel, 6.8% and 14.2% discontinued because of treatment-related adverse events (TRAEs), respectively; 1.4% and 1.0%, respectively, had TRAEs leading to death., Conclusion: Although statistical significance was not met, OS numerically improved with SG versus docetaxel, which was consistent across histologies. Clinically meaningful improvement in OS was noted in mNSCLC nonresponsive to last anti-PD-(L)1-containing regimen. SG was better tolerated than docetaxel and consistent with its known safety profile, with no new safety signals.

Recent advances in deep learning have led to the development of accurate and efficient models for various computer vision applications such as classification, segmentation, and detection. However, learning highly accurate models relies on the availability of large-scale annotated datasets. Due to this, model performance drops drastically when evaluated on label-scarce datasets having visually distinct images, termed as domain adaptation problem. There are a plethora of works to adapt classification and segmentation models to label-scarce target dataset through unsupervised domain adaptation. Considering that detection is a fundamental task in computer vision, many recent works have focused on developing novel domain adaptive detection techniques. Here, we describe in detail the domain adaptation problem for detection and present an extensive survey of the various methods. Furthermore, we highlight strategies proposed and the associated shortcomings. Subsequently, we identify multiple aspects of the problem that are most promising for future research. We believe that this survey shall be valuable to the pattern recognition experts working in the fields of computer vision, biometrics, medical imaging, and autonomous navigation by introducing them to the problem, and familiarizing them with the current status of the progress while providing promising directions for future research.

Compound 1 is formed by a microwave-assisted multicomponent reaction of 1-methylpiperidin-4-one, 2-amino-4-methoxy-6-methyl-1,3,5-triazine, and thiosemicarbazide, followed by the synthesis of Schiff base 2a-l with a variety of aldehydes. A comparison was made between the conventional and microwave methods, and the microwave approach was shown to be considerably superior to the classical method since it takes less time and produces higher yields. Several spectral investigations, including 1 H NMR, 13 C NMR, Mass, and IR spectroscopy, are used to characterize the complete series. In vitro antibacterial testing suggests that compounds 2c, 2f, and 2g are promising antibacterial agents, although compounds 2d, 2e, and 2l are effective antimycobacterial agents when compared to the conventional medicine Rifampicin. The docking score from docking studies is considerable, which validates the results of the biological examination. Molecular docking was performed on Escherichia coli DNA gyrase. According to the in silico ADME analysis, each drug molecule is ideal for use in terms of drug solubility, hydrogen bonding, and cell permeability., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

A 33-year-old female was admitted for community-acquired pneumonia. On presentation, she was tachypneic and tachycardic and leukocytosis at 28,900/µL. Chest imaging showed dense consolidation on the right upper lobe. Due to refractory worsening respiratory failure, she was intubated with mechanical ventilation. Initial bronchoscopy with culture data was negative. Extracorporeal membrane oxygenation was pursued on the fourth day. Repeat bronchoscopy revealed targetoid ulcerative lesions with erythema in the right middle, lower lobes and left lower lobe. We describe a case of herpes simplex virus pneumonia in an immunocompetent patient that occurred in the setting of acute bacterial infection., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Objective: Critical thinking and accurate case analysis is difficult to quantify even within the context of routine morbidity and mortality reporting. We designed and implemented a HIPAA-compliant adverse outcome reporting system that collects weekly resident assessments of clinical care across multiple domains (case summary, complications, error analysis, Clavien-Dindo Harm, cognitive bias, standard of care, and ACGME core competencies). We hypothesized that incorporation of this system into the residency program's core curriculum would allow for identification of areas of cognitive weakness or strength and provide a longitudinal evaluation of critical thinking development., Design: A validated, password-protected electronic platform linked to our electronic medical record was used to collect cases weekly in which surgical adverse events occurred. General surgery residents critiqued 1932 cases over a 4-year period from 3 major medical centers within our system. These data were reviewed by teaching faculty, corrected for accuracy and graded utilizing the software's critique algorithm. Grades were emailed to the residents at the time of the review, collected prospectively, stratified, and analyzed by post-graduate year (PGY). Evaluation of the resident scores for each domain and the resultant composite scores allowed for comparison of critical thinking skills across post-graduate year (PGY) over time., Setting: Data was collected from 3 independently ACGME-accredited surgery residency programs over 3 tertiary hospitals within our health system., Participants: General surgery residents in clinical PGY 1-5., Results: Residents scored highest in properly identifying ACGME core competencies and determining Clavien-Dindo scores (p < 0.006) with no improvement in providing accurate and concise clinical summaries. However, residents improved in recording data sufficient to identify error (p < 0.00001). A positive linear trend in median scores for all remaining domains except for cognitive bias was demonstrated (p < 0.001). Senior residents scored significantly higher than junior residents in all domains. Scores > 90% were never achieved., Conclusions: The use of an electronic standardized critique algorithm in the evaluation and assessment of adverse surgical case outcomes enabled the measure of residents' critical thinking skills. Feedback in the form of teaching faculty-facilitated discussion and emailed grades enhanced adult learning with a steady improvement in performance over PGY. Although residents improved with PGY, the data suggest that further improvement in all categories is possible. Implementing this standardized critique algorithm across PGY allows for evaluation of areas of individual resident weakness vs. strength, progression over time, and comparisons to peers. These data suggest that routine complication reporting may be enhanced as a critical thinking assessment tool and that improvement in critical thinking can be quantified. Incorporation of this platform into M&M conference has the potential to augment executive function and professional identity development., (Copyright © 2024 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Estimates of the land area occupied by wind energy differ by orders of magnitude due to data scarcity and inconsistent methodology. We developed a method that combines machine learning-based imagery analysis and geographic information systems and examined the land area of 318 wind farms (15,871 turbines) in the U.S. portion of the Western Interconnection. We found that prior land use and human modification in the project area are critical for land-use efficiency and land transformation of wind projects. Projects developed in areas with little human modification have a land-use efficiency of 63.8 ± 8.9 W/m 2 (mean ±95% confidence interval) and a land transformation of 0.24 ± 0.07 m 2 /MWh, while values for projects in areas with high human modification are 447 ± 49.4 W/m 2 and 0.05 ± 0.01 m 2 /MWh, respectively. We show that land resources for wind can be quantified consistently with our replicable method, a method that obviates >99% of the workload using machine learning. To quantify the peripheral impact of a turbine, buffered geometry can be used as a proxy for measuring land resources and metrics when a large enough impact radius is assumed (e.g., >4 times the rotor diameter). Our analysis provides a necessary first step toward regionalized impact assessment and improved comparisons of energy alternatives.

The accelerating magnetic resonance imaging (MRI) reconstruction process is a challenging ill-posed inverse problem due to the excessive under-sampling operation in k -space. In this paper, we propose a recurrent Transformer model, namely ReconFormer, for MRI reconstruction, which can iteratively reconstruct high-fidelity magnetic resonance images from highly under-sampled k -space data (e.g., up to 8× acceleration). In particular, the proposed architecture is built upon Recurrent Pyramid Transformer Layers (RPTLs). The core design of the proposed method is Recurrent Scale-wise Attention (RSA), which jointly exploits intrinsic multi-scale information at every architecture unit as well as the dependencies of the deep feature correlation through recurrent states. Moreover, benefiting from its recurrent nature, ReconFormer is lightweight compared to other baselines and only contains 1.1 M trainable parameters. We validate the effectiveness of ReconFormer on multiple datasets with different magnetic resonance sequences and show that it achieves significant improvements over the state-of-the-art methods with better parameter efficiency. The implementation code and pre-trained weights are available at https://github.com/guopengf/ReconFormer.

Hemoptysis is a complication of intrathoracic tumors, both primary and metastatic, and the risk may be increased by procedural interventions as well as Stereotactic Ablative Radiation (SAbR). The risk of hemoptysis with SAbR for lung cancer is well characterized, but there is a paucity of data about intrathoracic metastases. Here, we sought to evaluate the incidence of life-threatening/fatal hemoptysis (LTH) in patients with renal cell carcinoma (RCC) chest metastases with a focus on SAbR. We systematically evaluated patients with RCC at UT Southwestern Medical Center (UTSW) Kidney Cancer Program (KCP) from July 2005 to March 2020. We queried Kidney Cancer Explorer (KCE), a data portal with clinical, pathological, and experimental genomic data. Patients were included in the study based on mention of "hemoptysis" in clinical documentation, if they had a previous bronchoscopy, or had undergone SAbR to any site within the chest. Two hundred and thirty four patients met query criteria and their records were individually reviewed. We identified 10 patients who developed LTH. Of these, 4 had LTH as an immediate procedural complication whilst the remaining 6 had prior SAbR to ultra-central (UC; abutting the central bronchial tree) metastases. These 6 patients had a total of 10 lung lesions irradiated (UC, 8; central 1, peripheral 1), with a median total cumulative SAbR dose of 38 Gray (Gy/ lesion) (range: 25-50 Gy). Other risk factors included intrathoracic disease progression (n = 4, 67%), concurrent anticoagulant therapy (n = 1, 17%) and concurrent systemic therapy (n = 4, 67%). Median time to LTH from first SAbR was 26 months (range: 8-61 months). Considering that 130 patients received SAbR to a chest lesion during the study period, the overall incidence of LTH following SAbR was 4.6% (6/130). The patient population that received SAbR (n = 130) was at particularly high risk for complications, with 67 (52%) having two or more chest metastaes treated, and 29 (22%) receiving SAbR to three or more lesions. Overall, the risk of LTH following SAbR to a central or UC lesion was 10.5% (6/57). In conclusion, SAbR of RCC metastases located near the central bronchial tree may increase the risk of LTH., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cerebrovascular disease is a leading cause of death globally. Prevention and early intervention are known to be the most effective forms of its management. Non-invasive imaging methods hold great promises for early stratification, but at present lack the sensitivity for personalized prognosis. Resting-state functional magnetic resonance imaging (rs-fMRI), a powerful tool previously used for mapping neural activity, is available in most hospitals. Here we show that rs-fMRI can be used to map cerebral hemodynamic function and delineate impairment. By exploiting time variations in breathing pattern during rs-fMRI, deep learning enables reproducible mapping of cerebrovascular reactivity (CVR) and bolus arrival time (BAT) of the human brain using resting-state CO 2 fluctuations as a natural "contrast media". The deep-learning network is trained with CVR and BAT maps obtained with a reference method of CO 2 -inhalation MRI, which includes data from young and older healthy subjects and patients with Moyamoya disease and brain tumors. We demonstrate the performance of deep-learning cerebrovascular mapping in the detection of vascular abnormalities, evaluation of revascularization effects, and vascular alterations in normal aging. In addition, cerebrovascular maps obtained with the proposed method exhibit excellent reproducibility in both healthy volunteers and stroke patients. Deep-learning resting-state vascular imaging has the potential to become a useful tool in clinical cerebrovascular imaging., (© 2023. The Author(s).)

Keratosis pilaris (KP) is a common, hyperkeratotic skin condition characterized by small, folliculocentric papules with variable perifollicular erythema. We provide an updated review on the pathogenesis, clinical manifestations, and management of this common, and often annoying, finding. KP represents a family of follicular disorders, of which KP simplex is by far the most common. Other variants and rare subtypes include keratosis pilaris rubra, erythromelanosis follicularis faciei et colli, and the spectrum of keratosis pilaris atrophicans. Inherited mutations of the FLG gene and ABCA12 gene have been implicated etiologically. KP may be associated with ichthyosis vulgaris and palmar hyperlinearity, but less likely atopic dermatitis. Some potential differential diagnoses for KP include lichen spinulosus, phrynoderma, ichthyosis vulgaris, and trichostasis spinulosa. General cutaneous measures such as hydrating skin, avoiding long baths or showers, and using mild soaps or cleansers should be recommended. Topical keratolytic agents are first-line therapy, followed by topical retinoids and corticosteroids. Recent options include a variety of lasers and microdermabrasion if the patient is refractory to topical therapy.

A penicillin allergy testing service (PATS) assessed penicillin allergy in patients with hematologic malignancies; 17 patients who met criteria had negative skin testing. Patients who underwent penicillin challenge passed and were delabeled. Of delabeled patients, 87% received and tolerated β-lactams during follow-up. Providers found the PATS valuable., Competing Interests: All authors report no conflicts of interest relevant to this article., (© The Author(s) 2023.)

A 33-year-old male with a past medical history of asthma presented to the Emergency room with a three-day history of right-sided chest pain, productive cough with dark brown sputum, and shortness of breath. He was found to have right lower lobe consolidation consistent with acute pneumonia, and areas of non-homogenous density within the consolidation, suspicious of necrotizing pneumonia. Computed tomography (CT) of the chest with IV contrast revealed a large, irregular thick-walled cavitary mass involving the right middle lobe with surrounding ground glass cavitation. An extensive workup was negative, including a transbronchial biopsy. The case explains how a causative organism was detected., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Patel et al.)

Triclosan is a hydrophobic antimicrobial agent commonly employed in health care settings. While it exhibits broad-spectrum antibacterial properties, the gram-negative nosocomial opportunists Pseudomonas aeruginosa and Serratia marcescens are atypically refractory. Intrinsic resistance to triclosan in P. aeruginosa is largely due to its outer membrane impermeability properties for hydrophobic and bulky substances. The present study was undertaken to determine the relationship between triclosan and the outer cell envelopes of thirteen strains of ten Serratia species reported to be opportunistic pathogens in humans. General intrinsic resistance to hydrophobic and other outer membrane impermeant compounds was assessed using cultural selection, disk agar diffusion, and macrobroth dilution bioassays. Uptake of the hydrophobic fluorescent probe 1- N -phenylnapthylamine was assessed in four disparate strains of S. marcescens . Batch culture kinetics in the presence of combinations of triclosan and outer membrane permeabilizer compound 48/80 allowed analysis of outer membrane involvement in intrinsic resistance. Aggregate results revealed that individual species ranged in response to hydrophobic and bulky molecules from generally refractory to extremely susceptible. Moreover, susceptivity to triclosan sensitization by chemical disruption of outer membrane exclusionary properties differed markedly among species which exhibited intrinsic resistance to triclosan. These data suggest that disparate opportunistic pathogens within the genus Serratia differ phenotypically regarding the degree to which outer membrane exclusion contributes to intrinsic resistance for impermeant molecules in general, and triclosan specifically. Ancillary resistance mechanisms appear to contribute in some species and may involve constitutive multi-drug efflux systems. Importance A paucity of knowledge exists regarding the cellular and molecular mechanisms by which opportunistically pathogenic members of the genus Serratia are able to infect immunocompromised and otherwise susceptible individuals, and then evade chemotherapy. This is especially true for species other than Serratia marcescens and Serratia liquefaciens , although much remains to be learned with regard to the nature of key virulence factors and infection mechanisms which allow for the typically nosocomial acquisition of even these species. The research described in the present study will provide a better understanding of the contribution of outer cell envelope permeability properties to the pathogenicity of these opportunistic species in an ever-increasing susceptible patient population. It is our hope that greater knowledge of the basic biology of these organisms will contribute to the mitigation of suffering they cause in patients with underlying diseases., (©2023PublishedbyElsevierLtd.)

One-class novelty detectors are trained with examples of a particular class and are tasked with identifying whether a query example belongs to the same known class. Most recent advances adopt a deep auto-encoder style architecture to compute novelty scores for detecting novel class data. Deep networks have shown to be vulnerable to adversarial attacks, yet little focus is devoted to studying the adversarial robustness of deep novelty detectors. In this article, we first show that existing novelty detectors are susceptible to adversarial examples. We further demonstrate that commonly-used defense approaches for classification tasks have limited effectiveness in one-class novelty detection. Hence, we need a defense specifically designed for novelty detection. To this end, we propose a defense strategy that manipulates the latent space of novelty detectors to improve the robustness against adversarial examples. The proposed method, referred to as Principal Latent Space (PrincipaLS), learns the incrementally-trained cascade principal components in the latent space to robustify novelty detectors. PrincipaLS can purify latent space against adversarial examples and constrain latent space to exclusively model the known class distribution. We conduct extensive experiments on eight attacks, five datasets and seven novelty detectors, showing that PrincipaLS consistently enhances the adversarial robustness of novelty detection models.

A 60-year-old male with a past medical history of heart failure with reduced ejection fraction, obstructive sleep apnea, atrial flutter, and hypertension initially presented to the emergency department with a chief complaint of shortness of breath. He was diagnosed with COVID-19-induced acute hypoxic respiratory failure. Before his presentation to the emergency department, he was treated with a brief course of hydroxychloroquine, azithromycin, and prednisone. His initial hospitalization was relatively uncomplicated. He then presented back to the emergency department approximately five months later with chief complaints of continued dyspnea and increased work of breathing. On this presentation, he was noted to have a right-sided pneumothorax with a moderate right-sided pleural effusion. The effusion was drained through CT (computed tomography)-guided catheter insertion. Pleural fluid culture and sensitivity were negative, and a cartridge-based nucleic acid amplification test (CBNAAT) was not performed. He was discharged a few days later to home. Over the next several weeks, the patient had recurrent admissions and chest tube placements for unresolving hydropneumothorax. He eventually had a right-sided posterolateral thoracotomy performed. The tissue sample from the thoracotomy was noted to have positive gram staining for fungal hyphae consistent with aspergillosis. This was initially considered a contaminant and not treated with antifungal medication. Unfortunately, after the thoracotomy, the patient continued to have complications including subcutaneous emphysema and recurring hydropneumothoraces. He was taken for another procedure after a repeat CT showed intercostal herniation of the pleura between the fifth and sixth ribs. The herniation was excised, and the pleura was repaired. This pleural tissue was then sent to pathology and noted to have non-caseating granulomas consistent with aspergillosis. At this time, the patient was started on voriconazole. After initiating this medication, the patient's last chest x-ray showed stable findings of his chronic disease process with no new or worsening hydropneumothorax., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Patel et al.)

Background: Adult spinal intradural arachnoid cysts are rare pathologic entities with an unclear etiopathogenesis. These lesions can be dichotomized into primary (idiopathic) or secondary (related to inflammation, intradural surgery, or trauma) etiologies. Limited series have depicted optimal management strategies and clinical outcomes., Objective: To illustrate our experience with spinal intradural arachnoid cysts and to present a literature review of surgically treated cysts to elucidate the clinical and anatomic differences between etiologies., Methods: Institutional review revealed 29 patients. Various data were extracted from the medical record. Initial and follow-up symptomatologies of the surgical cohort were compared. The literature review included case series describing cysts managed surgically., Results: From patients treated surgically at our institution (22), there was a significant reduction in thoracic back pain postoperatively ( P = .034). A literature review yielded 271 additional cases. Overall, primary and secondary lesions accounted for 254 and 39 cases, respectively. Cysts of secondary origin were more likely localized ventral to the spinal cord ( P = .013). The rate of symptomatic improvement after surgical intervention for primary cysts was more than double than that of secondary cysts ( P < .001). Compared with primary etiologies, the rates of radiographic progression ( P = .032) and repeat surgery ( P = .041) were each more than double for secondary cysts., Conclusion: Surgical intervention for spinal intradural arachnoid cysts improves thoracic back pain. The literature supports surgical intervention for symptomatic primary spinal intradural arachnoid cysts with improved clinical outcomes. Surgery should be cautiously considered for secondary cysts given worse outcomes., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

The significant increase in monkeypox cases that was reported at the beginning of 2022 was notable. The resurgence of viral zoonosis is especially concerning, given the current and recent COVID-19 epidemic. There are worries that a new pandemic may be beginning due to the virus that causes monkeypox spreading so quickly. This article aimed to provide an overview of the epidemiology, pathogenesis, and clinical symptoms of monkeypox. It has been known that monkeypox was primarily prevalent in Central and West Africa, but in recent years, cases of monkeypox infections have been reported around the world. The transmission of the infection to humans has been connected to exposure to a diseased animal or person's excretions and secretions. Various studies indicate that monkeypox clinically manifests as fever, fatigue, and a rash of smallpox-like lesions and can cause various complications, including pneumonia, encephalitis, and sepsis, which, when not properly managed, can lead to death. Those living in remote and forested areas, taking care of individuals infected with monkeypox, and trading and taking care of exotic animals are some of the risk factors for monkeypox. Men having sex with men are also at higher risk of contracting monkeypox. When dealing with individuals who have high-risk factors and come with new-onset progressive rashes, it is necessary for clinicians to highly suspect monkeypox. This review will serve as reference material and a supplement to the existing literature that will assist in the proper management and prevention of monkeypox., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Patel et al.)

A 35-year-old female with a past medical history of untreated Hepatitis-C, and a history of intravenous (IV) drug use initially presented to the emergency department with chief complaints of gradual worsening sharp, constant left-sided chest pain with no radiation starting three weeks before presentation. In the emergency department (ED), she was afebrile, normotensive, and tachycardia with 99% oxygen saturation on room air. A physical exam revealed a well-developed Caucasian female, alert and oriented with moderate distress. Respiratory exam with symmetrical bilateral excursions without wheezes, crackles, or rhonchi. On cardiovascular exam, she was tachycardic with a regular rhythm without murmurs, rubs, or gallops. There was a 2 x 2 cm tender erythematous swelling on the left sternal border inferior to the clavicle. The neck was supple and negative for Jugular Venous Distension (JVD). Neurologically grossly intact. Abnormal laboratory findings included leukocytosis with neutrophilic predominance. The patient received intravenous (IV) antibiotics with broad-spectrum vancomycin, cefepime, and azithromycin and underwent computed tomography angiography (CTA) chest, revealing a 26.8 mm x 26.5 mm left anterior subapical pleural-based pulmonary mass-like lesion with central hypoattenuation in surrounding ground-glass changes. Biopsy of the left subapical pulmonary lesion results showed chronic inflammatory infiltrate. Unfortunately, the patient left the hospital against medical advice after supportive care and pain control. Our patient's history of intravenous drug use and active Hepatitis-C infection were typical risk factors associated with invasive infections. In the clinical context, leukocytosis with hypo-attenuated pulmonary lesion should raise suspicion for septic emboli, localized abscess pocket, infection by atypical organisms, infective endocarditis, and malignancy which was considered upon initial assessment., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Patel et al.)

Encephaloceles rarely develop following traumatic skull fractures. Given their low incidence, the clinical presentations and management strategies of these lesions are confined to case reports and limited case series. A systematic literature review was performed using PubMed, Ovid, and Web of Science databases to identify relevant articles using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 37 articles met inclusion criteria, including the case presented herein. These articles reported 52 traumatic encephaloceles. Mean patient age was 25.3 years (range 6 mo-66 y) with a male predominance (63%, 33/52). The most common bony defects resulting in encephalocele formation were the orbital roof (52%, 27/52), ethmoid (35%, 18/52), and sphenoid (10%, 5/52). Mean time from traumatic injury to initial presentation was 21.3 months (range 0 d-36 y) with a bimodal distribution split between immediately following the traumatic injury (57%, 26/46) or in a delayed manner (43%, 20/46). Common presentations of orbital roof, frontonasal, and temporal bone encephaloceles were exophthalmos (85%, 23/27), cerebrospinal fluid rhinorrhea (71%, 17/24), and hearing loss (100%, 4/4), respectively. Operative approach, repair technique, and materials used for encephalocele reduction were highly variable. Surgical intervention afforded definitive symptomatic improvement or resolution in the majority of cases (89%, 42/47). Clinical outcomes did not differ between orbital, frontonasal, or temporal bone encephaloceles ( P =0.438). Traumatic encephaloceles are a rare entity with diverse presenting symptomatology dependent upon the location of fracture dehiscence. Surgical intervention affords symptomatic improvement in the majority of cases irrespective of encephalocele location, time to presentation, or operative approach., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by Mutaz B. Habal, MD.)

Background: Although it is intuitive that nipple-sparing mastectomy in selected patients would result in excellent cosmetic outcomes and high patient satisfaction, studies of clinical outcomes and health-related quality of life are limited and show mixed results. This study aimed to use a propensity score-matching analysis to compare satisfaction and health-related quality-of-life outcomes in patients who underwent implant-based reconstruction following bilateral nipple-sparing mastectomy or skin-sparing mastectomy., Methods: A propensity score-matching analysis (1:1 matching, no replacement) was performed comparing patients undergoing nipple-sparing or skin-sparing mastectomy with immediate bilateral implant-based breast reconstruction. Patients with a history of any radiation therapy were excluded. Matched covariates included age, body mass index, race, smoking history, neoadjuvant chemotherapy, bra size, and history of psychiatric diagnosis. Outcomes of interest included BREAST-Q scores and complications., Results: The authors examined 1371 patients for matching and included 460 patients (nipple-sparing mastectomy, n = 230; skin-sparing mastectomy, n = 230) in the final analyses. The authors found no significant differences in baseline, cancer, and surgical characteristics between matched nipple-sparing and skin-sparing mastectomy patients, who also had similar profiles for surgical complications. Interestingly, the authors found that postoperative Satisfaction with Breasts scores and all other health-related quality-of-life domains were stable over a 3-year period and did not differ significantly between the two groups., Conclusions: Compared with skin-sparing mastectomy, bilateral nipple-sparing mastectomy did not improve patient-reported or clinical outcomes when combined with immediate implant-based reconstruction. The impact that nipple-sparing mastectomy may have on breast aesthetics and the ability of the BREAST-Q to gauge an aesthetic result following nipple-sparing mastectomy warrant further investigation., Clinical Question/level of Evidence: Therapeutic, III., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Background: The timing, route, and amount of nutrition for surgical patients with substantial caloric deficits remain active areas of study. Current guidelines are based on in-hospital days NPO after admission to the hospital. This historic process neglects the multiple days of caloric deficit patients experience prior to hospital admission., Aim: To determine the impact of pre-hospital caloric deficit (PHCD) for surgical patients on their outcomes., Methods: 313 patients admitted with a diagnosis of small bowel obstruction, pancreatitis, or diverticulitis were analyzed for their PHCD's. PHCD's were estimated using patient-reported days with significant emesis, and absent oral intake. Patients with PHCD's were compared to patients with no PHCD for length of stay, status on discharge, disposition, and 30-day readmission rate., Results: There were 313 patients and 42% of the patients were male. The median age was 65 years. Median number of days sick prior to hospital admission was 1 (IQR: 1 to 2). Median PHCD was 1882 kcal (IQR: 1355 to 3650). Median number of days NPO while in-hospital was 3 (IQR: 2 to 5). Median in-hospital caloric deficit was 4268 kcal (IQR: 2825 to 6610). No significant association was observed between discharge disposition, complication rate, ambulatory status, 30-day readmission rate and PHCD. In-hospital caloric deficit was associated with complications after surgery (p < 0.0001)., Conclusion: Small PHCD's in patients with SBO's, pancreatitis, or diverticulitis do not negatively affect their outcomes. Further research of patients with large PHCD's is needed to best treat surgical patients at risk for malnutrition.

Face presentation attack detection (fPAD) plays a critical role in the modern face recognition pipeline. An fPAD model with good generalization can be obtained when it is trained with face images from different input distributions and different types of spoof attacks. In reality, training data (both real face images and spoof images) are not directly shared between data owners due to legal and privacy issues. In this article, with the motivation of circumventing this challenge, we propose a federated face presentation attack detection (FedPAD) framework that simultaneously takes advantage of rich fPAD information available at different data owners while preserving data privacy. In the proposed framework, each data owner (referred to as data centers) locally trains its own fPAD model. A server learns a global fPAD model by iteratively aggregating model updates from all data centers without accessing private data in each of them. Once the learned global model converges, it is used for fPAD inference. To equip the aggregated fPAD model in the server with better generalization ability to unseen attacks from users, following the basic idea of FedPAD, we further propose a federated generalized face presentation attack detection (FedGPAD) framework. A federated domain disentanglement strategy is introduced in FedGPAD, which treats each data center as one domain and decomposes the fPAD model into domain-invariant and domain-specific parts in each data center. Two parts disentangle the domain-invariant and domain-specific features from images in each local data center. A server learns a global fPAD model by only aggregating domain-invariant parts of the fPAD models from data centers, and thus, a more generalized fPAD model can be aggregated in server. We introduce the experimental setting to evaluate the proposed FedPAD and FedGPAD frameworks and carry out extensive experiments to provide various insights about federated learning for fPAD.

We introduce a new large scale unconstrained crowd counting dataset (JHU-CROWD++) that contains "4,372" images with "1.51 million" annotations. In comparison to existing datasets, the proposed dataset is collected under a variety of diverse scenarios and environmental conditions. Specifically, the dataset includes several images with weather-based degradations and illumination variations, making it a very challenging dataset. Additionally, the dataset consists of a rich set of annotations at both image-level and head-level. Several recent methods are evaluated and compared on this dataset. The dataset can be downloaded from http://www.crowd-counting.com. Furthermore, we propose a novel crowd counting network that progressively generates crowd density maps via residual error estimation. The proposed method uses VGG16 as the backbone network and employs density map generated by the final layer as a coarse prediction to refine and generate finer density maps in a progressive fashion using residual learning. Additionally, the residual learning is guided by an uncertainty-based confidence weighting mechanism that permits the flow of only high-confidence residuals in the refinement path. The proposed Confidence Guided Deep Residual Counting Network (CG-DRCN) is evaluated on recent complex datasets, and it achieves significant improvements In errors.

Most methods for medical image segmentation use U-Net or its variants as they have been successful in most of the applications. After a detailed analysis of these "traditional" encoder-decoder based approaches, we observed that they perform poorly in detecting smaller structures and are unable to segment boundary regions precisely. This issue can be attributed to the increase in receptive field size as we go deeper into the encoder. The extra focus on learning high level features causes U-Net based approaches to learn less information about low-level features which are crucial for detecting small structures. To overcome this issue, we propose using an overcomplete convolutional architecture where we project the input image into a higher dimension such that we constrain the receptive field from increasing in the deep layers of the network. We design a new architecture for im- age segmentation- KiU-Net which has two branches: (1) an overcomplete convolutional network Kite-Net which learns to capture fine details and accurate edges of the input, and (2) U-Net which learns high level features. Furthermore, we also propose KiU-Net 3D which is a 3D convolutional architecture for volumetric segmentation. We perform a detailed study of KiU-Net by performing experiments on five different datasets covering various image modalities. We achieve a good performance with an additional benefit of fewer parameters and faster convergence. We also demonstrate that the extensions of KiU-Net based on residual blocks and dense blocks result in further performance improvements. Code: https://github.com/jeya-maria-jose/KiU-Net-pytorch.

Disruption of retromer-dependent endosomal trafficking is considered pathogenic in late-onset Alzheimer's disease (AD). Here, to investigate this disruption in the intact brain, we turn to a genetic mouse model where the retromer core protein VPS35 is depleted in hippocampal neurons, and then we replete VPS35 using an optimized viral vector protocol. The VPS35 depletion-repletion studies strengthen the causal link between the neuronal retromer and AD-associated neuronal phenotypes, including the acceleration of amyloid precursor protein cleavage and the loss of synaptic glutamate receptors. Moreover, the studies show that the neuronal retromer can regulate a distinct, dystrophic, microglia morphology, phenotypic of hippocampal microglia in AD. Finally, the neuronal and, in part, the microglia responses to VPS35 depletion were found to occur independent of tau. Showing that the neuronal retromer can regulate AD-associated pathologies in two of AD's principal cell types strengthens the link, and clarifies the mechanism, between endosomal trafficking and late-onset sporadic AD., Competing Interests: Declaration of interests S.A.S., G.A.P., and B.S. are on the Scientific Advisory Board of Retromer Therapeutics; G.A.P. is also on the Scientific Advisory Boards of MeiraGTx, AnnovisBio, Amicus Therapeutics, and Proclara Biosciences. B.S. is also on the advisory board of Annexon Biosciences and Neumora. Y.H.Q. is consulting for Retromer Therapeutics. Last, S.A.S., G.A.P., and Y.H.Q. are co-inventors on patent “Stabilization of retromer for the treatment of Alzheimer's disease and other neurodegenerative disorders” owned by Columbia University. S.A.S., S.S., and Y.H.Q. are co-inventors on patent “Precision targeted retromer therapeutics for the treatment of neurodegenerative diseases and disorders” owned by Columbia University., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Adversarial robustness of deep neural networks has been actively investigated. However, most existing defense approaches are limited to a specific type of adversarial perturbations. Specifically, they often fail to offer resistance to multiple attack types simultaneously, i.e., they lack multi-perturbation robustness. Furthermore, compared to image recognition problems, the adversarial robustness of video recognition models is relatively unexplored. While several studies have proposed how to generate adversarial videos, only a handful of approaches about defense strategies have been published in the literature. In this paper, we propose one of the first defense strategies against multiple types of adversarial videos for video recognition. The proposed method, referred to as MultiBN, performs adversarial training on multiple adversarial video types using multiple independent batch normalization (BN) layers with a learning-based BN selection module. With a multiple BN structure, each BN brach is responsible for learning the distribution of a single perturbation type and thus provides more precise distribution estimations. This mechanism benefits dealing with multiple perturbation types. The BN selection module detects the attack type of an input video and sends it to the corresponding BN branch, making MultiBN fully automatic and allowing end-to-end training. Compared to present adversarial training approaches, the proposed MultiBN exhibits stronger multi-perturbation robustness against different and even unforeseen adversarial video types, ranging from Lp-bounded attacks and physically realizable attacks. This holds true on different datasets and target models. Moreover, we conduct an extensive analysis to study the properties of the multiple BN structure.

A young female patient from Ahmedabad city presented with acute febrile illness and bicytopenia (leukopenia and thrombocytopenia). She returned to India after recent visit to East Africa. Human African Trypanosomiasis (Sleeping sickness) was diagnosed by identification of Trypanosoma brucei rhodesiense in peripheral blood smear. She treated successfully with suramin. In India, we account this as second case of HAT after first report before 18 years in the published literature., Competing Interests: Declaration of competing interest The author declare no conflicts of interest., (Copyright © 2021 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

The global pandemic of the novel coronavirus disease 2019 (COVID-19) has put tremendous pressure on the medical system. Imaging plays a complementary role in the management of patients with COVID-19. Computed tomography (CT) and chest X-ray (CXR) are the two dominant screening tools. However, difficulty in eliminating the risk of disease transmission, radiation exposure and not being cost-effective are some of the challenges for CT and CXR imaging. This fact induces the implementation of lung ultrasound (LUS) for evaluating COVID-19 due to its practical advantages of noninvasiveness, repeatability, and sensitive bedside property. In this paper, we utilize a deep learning model to perform the classification of COVID-19 from LUS data, which could produce objective diagnostic information for clinicians. Specifically, all LUS images are processed to obtain their corresponding local phase filtered images and radial symmetry transformed images before fed into the multi-scale residual convolutional neural network (CNN). Secondly, image combination as the input of the network is used to explore rich and reliable features. Feature fusion strategy at different levels is adopted to investigate the relationship between the depth of feature aggregation and the classification accuracy. Our proposed method is evaluated on the point-of-care US (POCUS) dataset together with the Italian COVID-19 Lung US database (ICLUS-DB) and shows promising performance for COVID-19 prediction.

Data-driven automatic approaches have demonstrated their great potential in resolving various clinical diagnostic dilemmas in neuro-oncology, especially with the help of standard anatomic and advanced molecular MR images. However, data quantity and quality remain a key determinant, and a significant limit of the potential applications. In our previous work, we explored the synthesis of anatomic and molecular MR image networks (SAMR) in patients with post-treatment malignant gliomas. In this work, we extend this through a confidence-guided SAMR (CG-SAMR) that synthesizes data from lesion contour information to multi-modal MR images, including T1-weighted ( [Formula: see text]), gadolinium enhanced [Formula: see text] (Gd- [Formula: see text]), T2-weighted ( [Formula: see text]), and fluid-attenuated inversion recovery ( FLAIR ), as well as the molecular amide proton transfer-weighted ( [Formula: see text]) sequence. We introduce a module that guides the synthesis based on a confidence measure of the intermediate results. Furthermore, we extend the proposed architecture to allow training using unpaired data. Extensive experiments on real clinical data demonstrate that the proposed model can perform better than current the state-of-the-art synthesis methods. Our code is available at https://github.com/guopengf/CG-SAMR.