Infiltrative Intramuscular Lipoma with Overlying Fascial Defect in the Anterior Thigh: A Case Report.

This case report details a unique presentation of an infiltrative intramuscular lipoma in the anterior thigh of a 51-year-old female with an overlying fascial defect. The patient reported a progressively enlarging left thigh mass associated with pain exacerbated by knee movement and exercise. MRI revealed a homogeneous intramuscular lipoma without contrast enhancement with a fascial defect. An 8 cm longitudinal incision exposed a 7 x 4 cm fascial defect overlying the lipomatous mass within the rectus femoris muscle. Pathological analysis confirmed an intramuscular lipoma without malignancy. Follow-ups at two, six, and 12 weeks demonstrated pain resolution and no soft tissue bulge. This case underscores the importance of distinguishing intramuscular lipomas from other neoplasms, such as lipomatosis and liposarcomas. The association of a fascial defect with intramuscular lipomas is unprecedented and may be due to the increased pressure on the fascia by the lipoma. The report emphasizes the role of MRI in diagnosis and appropriate surgical management, and highlights the need for further exploration into the etiology of fascial defects associated with intramuscular lipomas.

Lightness constancy in reality, in virtual reality, and on flat-panel displays.

Virtual reality (VR) displays are being used in an increasingly wide range of applications. However, previous work shows that viewers often perceive scene properties very differently in real and virtual environments and so realistic perception of virtual stimuli should always be a carefully tested conclusion, not an assumption. One important property for realistic scene perception is surface color. To evaluate how well virtual platforms support realistic perception of achromatic surface color, we assessed lightness constancy in a physical apparatus with real lights and surfaces, in a commercial VR headset, and on a traditional flat-panel display. We found that lightness constancy was good in all three environments, though significantly better in the real environment than on the flat-panel display. We also found that variability across observers was significantly greater in VR and on the flat-panel display than in the physical environment. We conclude that these discrepancies should be taken into account in applications where realistic perception is critical but also that in many cases VR can be used as a flexible alternative to flat-panel displays and a reasonable proxy for real environments.

Pen direct writing of SERRS-based lateral flow assays for detection of penicillin G in milk.

Direct pen writing offers versatile opportunities for development of low-cost tests for point-of-care applications. In this work a lateral flow immunoassay (LFIA) test was fabricated by hand "writing" immunoprobes onto hand-cut nitrocellulose strips with a commercial fountain pen. The qualitative capabilities of the test were extended by addition of a Raman reporter and consequent design and fabrication of a Surface Enhanced Resonant Raman Scattering (SERRS)-LFIA test. As proof-of-concept, dual detection of penicillin G was achieved in milk with a visual LOD of 20 ppm and a dynamic range of 0.03-97.5 ppm. Evaluation against equivalent tests performed with conventionally prepared LFIA strips showed comparable results, thus demonstrating the validity of the test. These results demonstrate the potential for further decrease in cost and consequent broader use of LFIA tests in remote regions and resource-limited environments.

Development of Cell-Free Transcription-Translation Systems in Three Soil Pseudomonads.

In vitro transcription-translation (TX-TL) can enable faster engineering of biological systems. This speed-up can be significant, especially in difficult-to-transform chassis. This work shows the successful development of TX-TL systems using three soil-derived wild-type Pseudomonads known to promote plant growth: Pseudomonas synxantha, Pseudomonas chlororaphis, and Pseudomonas aureofaciens. All three species demonstrated multiple sonication, runoff, and salt conditions producing detectable protein synthesis. One of these new TX-TL systems, P. synxantha, demonstrated a maximum protein yield of 2.5 µM at 125 proteins per DNA template, a maximum protein synthesis rate of 20 nM/min, and a range of DNA concentrations with a linear correspondence with the resulting protein synthesis. A set of different constitutive promoters driving mNeonGreen expression were tested in TX-TL and integrated into the genome, showing similar normalized strengths for in vivo and in vitro fluorescence. This correspondence between the TX-TL-derived promoter strength and the in vivo promoter strength indicates that these lysate-based cell-free systems can be used to characterize and engineer biological parts without genomic integration, enabling a faster design-build-test cycle.

Engineering the Soil Bacterium Pseudomonas synxantha 2-79 into a Ratiometric Bioreporter for Phosphorus Limitation.

Microbial bioreporters hold promise for addressing challenges in medical and environmental applications. However, the difficulty in ensuring their stable persistence and function within the target environment remains a challenge. One strategy is to integrate information about the host strain and target environment into the design-build-test cycle of the bioreporter itself. Here, we present a case study for such an environmentally motivated design process by engineering the wheat commensal bacterium Pseudomonas synxantha 2-79 into a ratiometric bioreporter for phosphorus limitation. Comparative analysis showed that an exogenous P-responsive promoter outperformed its native counterparts. This reporter can selectively sense and report phosphorus limitation at plant-relevant concentrations of 25-100 µM without cross-activation from carbon or nitrogen limitation or high cell densities. Its performance is robust over a field-relevant pH range (5.8-8), and it responds only to inorganic phosphorus, even in the presence of common soil organic P. Finally, we used fluorescein-calibrated flow cytometry to assess whether the reporter's performance in shaken liquid culture predicts its performance in soil, finding that although the reporter is still functional at the bulk level, its variability in performance increases when grown in a soil slurry as compared to planktonic culture, with a fraction of the population not expressing the reporter proteins. Together, our environmentally aware design process provides an example of how laboratory bioengineering efforts can generate microbes with a greater promise to function reliably in their applied contexts.

TRILL: ORCHESTRATING MODULAR DEEP-LEARNING WORKFLOWS FOR DEMOCRATIZED, SCALABLE PROTEIN ANALYSIS AND ENGINEERING.

Deep-learning models have been rapidly adopted by many fields, partly due to the deluge of data humanity has amassed. In particular, the petabases of biological sequencing data enable the unsupervised training of protein language models that learn the "language of life." However, due to their prohibitive size and complexity, contemporary deep-learning models are often unwieldy, especially for scientists with limited machine learning backgrounds. TRILL (TRaining and Inference using the Language of Life) is a platform for creative protein design and discovery. Leveraging several state-of-the-art models such as ESM-2, DiffDock, and RFDiffusion, TRILL allows researchers to generate novel proteins, predict 3-D structures, extract high-dimensional representations of proteins, functionally classify proteins and more. What sets TRILL apart is its ability to enable complex pipelines by chaining together models and effectively merging the capabilities of different models to achieve a sum greater than its individual parts. Whether using Google Colab with one GPU or a supercomputer with hundreds, TRILL allows scientists to effectively utilize models with millions to billions of parameters by using optimized training strategies such as ZeRO-Offload and distributed data parallel. Therefore, TRILL not only bridges the gap between complex deep-learning models and their practical application in the field of biology, but also simplifies the orchestration of these models into comprehensive workflows, democratizing access to powerful methods. Documentation: https://trill.readthedocs.io/en/latest/home.html.

Differentiating Between Obturator and Inferior Epigastric Arterial Injury in Traumatic Pelvic Hemorrhage: A Case Report.

The pubic branches of the inferior epigastric and obturator arteries are subject to injury from pelvic trauma or surgery within the retropubic space. Such injuries can result in severe internal hemorrhage that can lead to hemodynamic instability if not adequately controlled. Due to their anatomical proximity and anastomosis, it is critical to determine which artery is hemorrhaging in order to provide accurate embolization. In the presented case, a geriatric patient suffered a fall from standing height that resulted in bilateral and multiple pelvic fractures. CT angiography of the abdomen demonstrated active left-sided pelvic hemorrhage and a resultant 10 cm anterior extraperitoneal hematoma, likely exacerbated by existing anticoagulant usage. Urgent embolization of the inferior epigastric artery was performed in addition to multiple transfusions. The patient recovered without any procedural complications and was later discharged for rehabilitation.

A Rare Case of Gastric Intramural Hematoma Secondary to Hemorrhagic Pancreatitis.

Gastric intramural hematoma (GIH) is a contained hemorrhage located within the layers that comprise the wall of the stomach. It is a rare condition that has a variety of etiologies. Pancreatitis-induced GIH is an even rarer phenomenon, with only a handful of documented cases in the medical literature. In the current case, a patient presented with chronic abdominal pain for the past two months, with an acute worsening of symptoms. CT imaging confirmed a large, stable GIH with concomitant pancreatitis, likely alcohol-induced. Diagnostic laparoscopy was performed in response to worsening hemodynamic status, which confirmed hemorrhagic pancreatitis as the likely cause of the GIH formation. Jackson-Pratt (JP) drains were placed, and the patient was subsequently discharged. The patient returned one month later with an acute exacerbation of pancreatitis; however, interval improvement of the GIH was observed. The patient was transferred to outpatient care for continued conservative treatment without any further return visits.

Biliary Outlet Obstruction Due to Pancreatic Calculi in a Post-cholecystectomy Patient.

Chronic pancreatitis has been shown to cause various pathologies, such as biliary strictures and pancreatic malignancies, which can in turn result in biliary outlet obstruction. However, a pancreatic calculus itself resulting in biliary obstruction has been far less observed. The patient in question had a documented history of chronic alcoholism and received a cholecystectomy decades prior to the onset of cholestatic symptoms. Cholangiography demonstrated no indication of biliary stricture formation, nor was there radiological evidence of pancreatic pseudocyst or malignant formation. CT evidence across a decade of time established a storyline of pancreatic calculi formation, migration, and resultant biliary obstruction. Subsequent endoscopic sphincterectomy, pancreatic calculi removal, and biliary tree stent placement resulted in laboratory value normalization and clinical symptom resolution.

Use of Percutaneous Cholecystostomy for the Management of Complicated Cholecystitis Causing Gastric Outlet Obstruction in an Elderly Patient.

The management of complicated cholecystitis in an elderly patient can present a complex clinical decision for surgeons. There is literature supporting the use of immediate laparoscopic cholecystectomy for cases of uncomplicated cholecystitis in elderly patients and complicated cholecystitis in the general population. There are, however, no clear guidelines for treating the unique presentation of an elderly patient with complicated cholecystitis. This is likely due to the many clinical risk factors that must be considered when caring for these complex patients often with many medical comorbidities. In this report, we present the case of an 81-year-old male with complicated chronic cholecystitis leading to the exceedingly rare complication of gastric outlet obstruction. The patient was successfully treated with percutaneous cholecystostomy tube placement and interval subtotal laparoscopic cholecystectomy.

Adult Radiographic Presentation of Corpus Callosal Agenesis With a Single Interhemispheric Cyst and Dandy-Walker Malformation: A Case Report.

Agenesis or dysgenesis of the corpus callosum may occur due to ischemic, toxic, traumatic, or another insult to the fetus in the first trimester. Occasionally, such a malformation is associated with an interhemispheric cyst, among other central nervous system anomalies. Holoprosencephaly tends to mimic this radiographic presentation, which is where key imaging findings are helpful to differentiate between these entities. We present a 56-year-old male patient who was found to have a monoventricle, corpus callosum agenesis, interhemispheric cyst, and a Dandy-Walker malformation. The patient presented with a right acetabular fracture with computed tomography (CT) of the brain revealing the congenital brain abnormalities. The patient's past medical history was notable for a seizure disorder identified during early adulthood. The CT scan of the head revealed a large monoventricle with an associated midline dorsal interhemispheric cyst and a Dandy-Walker malformation. The absence of both the corpus callosum and septum pellucidum was noted, with the presence of a monoventricle, leading to an initial differential of holoprosencephaly. Further review of the findings suggested instead a rare congenital presentation consisting of corpus callosum agenesis and an interhemispheric cyst. This case highlights a unique radiographic presentation of multiple brain anomalies, rarely presented in non-pediatric literature, which may help determine appropriate surgical and medical management for similarly affected adult individuals.

Silver nanoparticles - laser induced graphene (Ag NPs - LIG) hybrid electrodes for sensitive electrochemical-surface enhanced Raman spectroscopy (EC-SERS) detection.

This paper presents a novel approach for the fabrication of low cost Electrochemical-Surface Enhanced Raman Scattering (EC-SERS) sensing platforms. Laser Induced Graphene (LIG) electrodes were readily fabricated by direct laser writing of polyimide tapes and functionalized with silver nanoparticles (Ag NPs) to obtain hybrid Ag NPs - LIG electrodes suitable for EC-SERS analysis. Detection was achieved by coupling a handheld potentiostat with a Raman spectrograph, enabling measurement of SERS spectra of target analytes generated during voltage sweeps in the 0.0 to -1.0 V interval range. The sensing capabilities of the fabricated system were first tested with model molecule 4-aminobenzenethiol (4-ABT). Following sensitive detection of 4-ABT, EC-SERS analysis of food contaminant melamine in milk and antibiotic difloxacin hydrochloride (DIF) in river water was demonstrated, achieving sensitive detection of both analytes without pre-treatment steps. The easiness of fabrication, versatility of design, rapid analysis time and potential miniaturization of the system make Ag NPs - LIG electrodes suitable for a large range of in situ applications in the field of food monitoring and for environmental analysis.

Addressable and adaptable intercellular communication via DNA messaging.

Engineered consortia are a major research focus for synthetic biologists because they can implement sophisticated behaviors inaccessible to single-strain systems. However, this functional capacity is constrained by their constituent strains' ability to engage in complex communication. DNA messaging, by enabling information-rich channel-decoupled communication, is a promising candidate architecture for implementing complex communication. But its major advantage, its messages' dynamic mutability, is still unexplored. We develop a framework for addressable and adaptable DNA messaging that leverages all three of these advantages and implement it using plasmid conjugation in E. coli. Our system can bias the transfer of messages to targeted receiver strains by 100- to 1000-fold, and their recipient lists can be dynamically updated in situ to control the flow of information through the population. This work lays the foundation for future developments that further utilize the unique advantages of DNA messaging to engineer previously-inaccessible levels of complexity into biological systems.

Use of Remote Cardiorespiratory Monitoring is Associated with a Reduction in Hospitalizations for Subjects with COPD.

Background: Chronic obstructive pulmonary disease (COPD) is prevalent and results in high healthcare resource utilization. The largest impact on health status and proportion of healthcare costs in COPD are related to hospitalizations for acute exacerbations. Accordingly, the Centers for Medicare & Medicaid Services have advocated for remote patient monitoring (RPM) to aid in chronic disease management. However, there has been a lack of evidence for the effectiveness of RPM in reducing the need for unplanned hospitalizations for patients with COPD. Methods: This pre/post study was a retrospective analysis of unplanned hospitalizations in a cohort of COPD subjects started on RPM at a large, outpatient pulmonary practice. The study included all subjects with at least one unplanned, all-cause hospitalization or emergency room visit in the prior year, who had elected to enroll in an RPM service for assistance with clinical management. Additional inclusion criteria included being on RPM for at least 12 months and a patient of the practice for at least two years (12 months pre- and post-initiation of RPM). Results: The study included 126 subjects. RPM was associated with a significantly lower rate of unplanned hospitalizations per patient per year (1.09 ± 0.07 versus 0.38 ± 0.06, P<0.001). Conclusion: Unplanned, all-cause hospitalization rates were lower in subjects started on RPM for COPD when compared to their prior year. These results support the potential of RPM to improve the long-term management of COPD.

Postoperative Infection and Revision Surgery Rates in Foot and Ankle Surgery Without Routine Prescription of Prophylactic Antibiotics.

INTRODUCTION: Surgical site infections (SSIs) are associated with patient morbidity and increased healthcare costs. Limited literature in foot and ankle surgery provides guidance about routine administration of postoperative antibiotic prophylaxis. The purpose of this study was to examine the incidence and revision surgery rates of SSI in outpatient foot and ankle surgeries in patients not receiving oral postoperative antibiotic prophylaxis. METHODS: A retrospective review of all outpatient surgeries (n = 1517) conducted by a single surgeon in a tertiary referral academic center was conducted through electronic medical records. Incidence of SSI, revision surgery rate, and associated risk factors were determined. The median follow-up was 6 months. RESULTS: Postoperative infection occurred in 2.9% (n = 44) of the surgeries conducted, with 0.9% of patients (n = 14) requiring return to the operating room. Thirty patients (2.0%) were diagnosed with simple superficial infections, which resolved with local wound care and oral antibiotics. Diabetes (adjusted odds ratio, 2.09; 95% confidence interval, 1.00 to 4.38; P = 0.049) and increasing age (adjusted odds ratio, 1.02; 95% confidence interval, 1.00 to 1.04; P = 0.016) were significantly associated with postoperative infection. DISCUSSION: This study demonstrated low postoperative infection and revision surgery rates without the routine prescription of prophylactic postoperative antibiotics. Increasing age and diabetes are signficant risk factors for developing a postoperative infection.

Characterization of Integrase and Excisionase Activity in a Cell-Free Protein Expression System Using a Modeling and Analysis Pipeline.

We present a full-stack modeling, analysis, and parameter identification pipeline to guide the modeling and design of biological systems starting from specifications to circuit implementations and parametrizations. We demonstrate this pipeline by characterizing the integrase and excisionase activity in a cell-free protein expression system. We build on existing Python tools─BioCRNpyler, AutoReduce, and Bioscrape─to create this pipeline. For enzyme-mediated DNA recombination in a cell-free system, we create detailed chemical reaction network models from simple high-level descriptions of the biological circuits and their context using BioCRNpyler. We use Bioscrape to show that the output of the detailed model is sensitive to many parameters. However, parameter identification is infeasible for this high-dimensional model; hence, we use AutoReduce to automatically obtain reduced models that have fewer parameters. This results in a hierarchy of reduced models under different assumptions to finally arrive at a minimal ODE model for each circuit. Then, we run sensitivity analysis-guided Bayesian inference using Bioscrape for each circuit to identify the model parameters. This process allows us to quantify integrase and excisionase activity in cell extracts enabling complex-circuit designs that depend on accurate control over protein expression levels through DNA recombination. The automated pipeline presented in this paper opens up a new approach to complex circuit design, modeling, reduction, and parametrization.

MmCMS: mouse models' consensus molecular subtypes of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) primary tumours are molecularly classified into four consensus molecular subtypes (CMS1-4). Genetically engineered mouse models aim to faithfully mimic the complexity of human cancers and, when appropriately aligned, represent ideal pre-clinical systems to test new drug treatments. Despite its importance, dual-species classification has been limited by the lack of a reliable approach. Here we utilise, develop and test a set of options for human-to-mouse CMS classifications of CRC tissue. METHODS: Using transcriptional data from established collections of CRC tumours, including human (TCGA cohort; n = 577) and mouse (n = 57 across n = 8 genotypes) tumours with combinations of random forest and nearest template prediction algorithms, alongside gene ontology collections, we comprehensively assess the performance of a suite of new dual-species classifiers. RESULTS: We developed three approaches: MmCMS-A; a gene-level classifier, MmCMS-B; an ontology-level approach and MmCMS-C; a combined pathway system encompassing multiple biological and histological signalling cascades. Although all options could identify tumours associated with stromal-rich CMS4-like biology, MmCMS-A was unable to accurately classify the biology underpinning epithelial-like subtypes (CMS2/3) in mouse tumours. CONCLUSIONS: When applying human-based transcriptional classifiers to mouse tumour data, a pathway-level classifier, rather than an individual gene-level system, is optimal. Our R package enables researchers to select suitable mouse models of human CRC subtype for their experimental testing.

Risk of hospitalization in a sample of COVID-19 patients with and without chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: Patients with chronic obstructive pulmonary disease (COPD) may have worse coronavirus disease-2019 (COVID-19)-related outcomes. We compared COVID-19 hospitalization risk in patients with and without COPD. METHODS: This retrospective cohort study included patients ≥40 years, SARS-CoV-2 positive, and with Kaiser Permanente Northern California membership ≥1 year before COVID-19 diagnosis (electronic health records and claims data). COVID-19-related hospitalization risk was assessed by sequentially adjusted logistic regression models and stratified by disease severity. Secondary outcome was death/hospice referral after COVID-19. RESULTS AND DISCUSSION: Of 19,558 COVID-19 patients, 697 (3.6%) had COPD. Compared with patients without COPD, COPD patients were older (median age: 69 vs 53 years); had higher Elixhauser Comorbidity Index (5 vs 0) and more median baseline outpatient (8 vs 4), emergency department (2 vs 1), and inpatient (2 vs 1) encounters. Unadjusted analyses showed increased odds of hospitalization with COPD (odds ratio [OR]: 3.93; 95% confidence interval [CI]: 3.40-4.60). After full risk adjustment, there were no differences in odds of hospitalization (OR: 1.14, 95% CI: 0.93-1.40) or death/hospice referral (OR: 0.96, 95% CI: 0.72-1.27) between patients with and without COPD. Primary/secondary outcomes did not differ by COPD severity, except for higher odds of hospitalization in COPD patients requiring supplemental oxygen versus those without COPD (OR: 1.84, 95% CI: 1.02-3.33). CONCLUSIONS: Except for hospitalization among patients using supplemental oxygen, no differences in odds of hospitalization or death/hospice referral were observed in the COVID-19 patient sample depending on whether they had COPD.

Persistent Steroid Exposure Before Coronavirus Disease 2019 Diagnosis and Risk of Hospitalization in Patients With Chronic Obstructive Pulmonary Disease.

Background: It is unclear whether persistent inhaled steroid exposure in chronic obstructive pulmonary disease (COPD) patients before coronavirus disease 2019 (COVID-19) is associated with hospitalization risk. Objective: Our objective was to examine the association between persistent steroid exposure and COVID-19-related hospitalization risk in COPD patients. Study Design and Methods: This retrospective cohort study used electronic health records from the Kaiser Permanente Northern California health care system (February 2, 2020, to September 30, 2020) for patients aged ≥40 years with COPD and a positive polymerase chain reaction test result for COVID-19. Primary exposure was persistent oral and/or inhaled steroid exposure defined as ≥6 months of prescriptions filled in the year before the COVID-19 diagnosis. Multivariable logistic regression was performed for the primary outcome of COVID-19-related hospitalization or death/hospice referral. Steroid exposure in the month before a COVID-19 diagnosis was a covariate. Results: Of >4.3 million adults, 697 had COVID-19 and COPD, of whom 270 (38.7%) had COVID-19-related hospitalizations. Overall, 538 (77.2%) were neither exposed to steroids in the month before COVID-19 diagnosis nor persistently exposed; 53 (7.6%) were exposed in the month before but not persistently; 23 (3.3%) were exposed persistently but not in the month before; and 83 (11.9%) were exposed both persistently and in the month before. Adjusting for all confounders including steroid use in the month before, the odds ratio for hospitalization was 0.77 (95% confidence interval 0.41-1.46) for patients persistently exposed to steroids before a COVID-19 diagnosis. Interpretation: No association was observed between persistent steroid exposure and the risk of COVID-19-related hospitalization in COPD patients.