DSG-GAN:A dual-stage-generator-based GAN for cross-modality synthesis from PET to CT.

PET/CT devices typically use CT images for PET attenuation correction, leading to additional radiation exposure. Alternatively, in a standalone PET imaging system, attenuation and scatter correction cannot be performed due to the absence of CT images. Therefore, it is necessary to explore methods for generating pseudo-CT images from PET images. However, traditional PET-to-CT synthesis models encounter conflicts in multi-objective optimization, leading to disparities between synthetic and real images in overall structure and texture. To address this issue, we propose a staged image generation model. Firstly, we construct a dual-stage generator, which synthesizes the overall structure and texture details of images by decomposing optimization objectives and employing multiple loss functions constraints. Additionally, in each generator, we employ improved deep perceptual skip connections, which utilize cross-layer information interaction and deep perceptual selection to effectively and selectively leverage multi-level deep information and avoid interference from redundant information. Finally, we construct a context-aware local discriminator, which integrates context information and extracts local features to generate fine local details of images and reasonably maintain the overall coherence of the images. Experimental results demonstrate that our approach outperforms other methods, with SSIM, PSNR, and FID metrics reaching 0.8993, 29.6108, and 29.7489, respectively, achieving the state-of-the-art. Furthermore, we conduct visual experiments on the synthesized pseudo-CT images in terms of image structure and texture. The results indicate that the pseudo-CT images synthesized in this study are more similar to real CT images, providing accurate structure information for clinical disease analysis and lesion localization.

The Impact of the Post-Traumatic Facial Reconstruction on Postoperative Weight Loss.

Objectives: To identify risk factors and evaluate the impact of various facial fractures and reconstruction surgeries on postoperative weight change. Methods: Retrospective, monocentric study was performed at a tertiary care center. Medical history, type and mechanism of fracture, operative factors, and postoperative weights at follow-up appointments for 145 adult patients undergoing surgical repair for maxillofacial fractures were collected. Further information was obtained on postoperative diet and whether patients received maxillomandibular fixation (MMF). Univariate and multivariate analyses were utilized to evaluate effects of surgical reconstruction after facial trauma on postoperative weight loss. Results: Patients lost 3.2 ± 4.9 kg (95% confidence interval = 2.7-4.1, P < .0001) on average, with maximum loss between date of surgery and first follow-up. Univariate analysis demonstrated that intensive care unit admission (5.9 kg, SD 5.4, P = .001), nasogastric tube placement (5.1 kg, SD 4.6, P = .012), and MMF (4.4 kg, SD 5.4, P < .0001) were associated with more severe weight loss. Multivariate analyses showed that only MMF remained a significant risk factor for increased weight loss (avg. 6.0, standard error 1.93, t value 3.11, P = .0024). Conclusions: We report significant weight loss following facial trauma and reconstruction, which emphasizes the need to perform further studies on nutrition protocols for this patient population to optimize wound healing.

Contraception in patients with liver disease and liver transplant.

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Machine learning approaches to identify systemic lupus erythematosus in anti-nuclear antibody-positive patients using genomic data and electronic health records.

BACKGROUND: Although the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus (SLE) has required at least a positive anti-nuclear antibody (ANA) titer (≥ 1:80), it remains challenging for clinicians to identify patients with SLE. This study aimed to develop a machine learning (ML) approach to assist in the detection of SLE patients using genomic data and electronic health records. METHODS: Participants with a positive ANA (≥ 1:80) were enrolled from the Taiwan Precision Medicine Initiative cohort. The Taiwan Biobank version 2 array was used to detect single nucleotide polymorphism (SNP) data. Six ML models, Logistic Regression, Random Forest (RF), Support Vector Machine, Light Gradient Boosting Machine, Gradient Tree Boosting, and Extreme Gradient Boosting (XGB), were used to identify SLE patients. The importance of the clinical and genetic features was determined by Shapley Additive Explanation (SHAP) values. A logistic regression model was applied to identify genetic variations associated with SLE in the subset of patients with an ANA equal to or exceeding 1:640. RESULTS: A total of 946 SLE and 1,892 non-SLE controls were included in this analysis. Among the six ML models, RF and XGB demonstrated superior performance in the differentiation of SLE from non-SLE. The leading features in the SHAP diagram were anti-double strand DNA antibodies, ANA titers, AC4 ANA pattern, polygenic risk scores, complement levels, and SNPs. Additionally, in the subgroup with a high ANA titer (≥ 1:640), six SNPs positively associated with SLE and five SNPs negatively correlated with SLE were discovered. CONCLUSIONS: ML approaches offer the potential to assist in diagnosing SLE and uncovering novel SNPs in a group of patients with autoimmunity.

I Am Worried I Have Sciatica-What Do I Need to Know?

This JAMA Internal Medicine Patient Page reviews sciatica, its symptoms, and treatment options for those who have it.

Dynamic elevation of aromatic amino acids in Hepatitis C Virus induced cirrhosis after a standard meal.

BACKGROUND AIMS: Perturbations in aromatic (AAA) and branched-chain amino acids (BCAA) are seen in decompensated liver disease. The aim of this study was to evaluate the dynamic, post-prandial relationship between hepatitis C virus (HCV) induced liver disease and amino acid concentrations in patients with compensated liver disease. METHODS: HCV-infected patients underwent a baseline liver biopsy to determine Ishak Fibrosis and evaluate the liver transcriptome. Patients ate a standard meal and underwent peripheral vein sampling at defined intervals. Quantitative analysis of amino acids was preformed using liquid chromatography-tandem mass spectrometry. RESULTS: At baseline there was no difference in AAA and BCAA concentrations between cirrhotic and non-cirrhotic patients. After a standard meal, AAA, but not BCAA, were elevated in cirrhotic patients compared to non-cirrhotic at every time point. The Hepquant shunt fraction was significantly higher in cirrhotic patients and positively correlated with AAA at all time points, but not BCAA. Analysis of the hepatic transcriptome demonstrated greater downregulation of the AAA degradation pathways than the BCAA degradation pathways. CONCLUSION: At baseline cirrhotic patients with compensated liver disease have adequate reserve liver function to metabolize AAA and BCAA. When faced with a metabolic stressor, such as a standard meal, cirrhotic patients are less able to metabolize the increased load of AAA. This impairment correlates with porto-systemic shunting. Further evaluation of AAA in compensated liver disease might further the understanding of the liver-muscle- axis and the role it may play in development of sarcopenia in liver disease.

Geometric frustration of hard-disk packings on cones.

Conical surfaces pose an interesting challenge to crystal growth: A crystal growing on a cone can wrap around and meet itself at different radii. We use a disk-packing algorithm to investigate how this closure constraint can geometrically frustrate the growth of single crystals on cones with small opening angles. By varying the crystal seed orientation and cone angle, we find that-except at special commensurate cone angles-crystals typically form a seam that runs along the axial direction of the cone, while near the tip, a disordered particle packing forms. We show that the onset of disorder results from a finite-size effect that depends strongly on the circumference and not on the seed orientation or cone angle. This finite-size effect occurs also on cylinders, and we present evidence that on both cylinders and cones, the defect density increases exponentially as circumference decreases. We introduce a simple model for particle attachment at the seam that explains the dependence on the circumference. Our findings suggest that the growth of single crystals can become frustrated even very far from the tip when the cone has a small opening angle. These results may provide insights into the observed geometry of conical crystals in biological and materials applications.

Machine-learning-based Structural Analysis of Interactions between Antibodies and Antigens.

Computational analysis of paratope-epitope interactions between antibodies and their corresponding antigens can facilitate our understanding of the molecular mechanism underlying humoral immunity and boost the design of new therapeutics for many diseases. The recent breakthrough in artificial intelligence has made it possible to predict protein-protein interactions and model their structures. Unfortunately, detecting antigen-binding sites associated with a specific antibody is still a challenging problem. To tackle this challenge, we implemented a deep learning model to characterize interaction patterns between antibodies and their corresponding antigens. With high accuracy, our model can distinguish between antibody-antigen complexes and other types of protein-protein complexes. More intriguingly, we can identify antigens from other common protein binding regions with an accuracy of higher than 70% even if we only have the epitope information. This indicates that antigens have distinct features on their surface that antibodies can recognize. Additionally, our model was unable to predict the partnerships between antibodies and their particular antigens. This result suggests that one antigen may be targeted by more than one antibody and that antibodies may bind to previously unidentified proteins. Taken together, our results support the precision of antibody-antigen interactions while also suggesting positive future progress in the prediction of specific pairing.

"It's What We Can Do Right Now": Professional Identity Formation Among Internal Medicine Residents During the COVID-19 Pandemic.

PURPOSE: The COVID-19 pandemic represents a consequential moment of disruption for medical training that has far-reaching implications for professional identity formation (PIF). To date, this has not been studied. As medical education grapples with a postpandemic era, it is essential to gain insight into how the pandemic has influenced PIF to better support its positive influences and mitigate its more detrimental effects. This study examined how PIF occurred during the COVID-19 pandemic to better adapt future medical training. METHOD: Constructivist grounded theory guided the iterative data collection and analyses. The authors conducted semistructured group interviews with 24 Ontario internal medicine residents in postgraduate years (PGYs) 1 to 3 between November 2020 and July 2021. Participants were asked to reflect on their day-to-day clinical and learning experiences during the pandemic. RESULTS: Twenty-four internal medicine residents were interviewed (12 PGY-1 [50.0%], 9 PGY-2 [37.5%], and 3 PGY-3 [12.5%]). Participants described how navigating patient care and residency training through the pandemic consistently drew their attention to various system problems. How participants responded to these problems was shaped by an interplay among their personal values, their level of personal wellness or burnout, self-efficacy, institutional values, and the values of their supervisors and work community. As they were influenced by these factors, some were led toward acting on the problem(s) they identified, whereas others had a sense of resignation and deferred action. These interactions were evident in participants' experiences with communication, advocacy, and learning. CONCLUSIONS: Residents' professional identities are continuously shaped by how they perceive, reconcile, and address various challenges. As residents navigate tensions between personally held values and apparent system values, individuals in supervisory positions should be mindful of their influence as role models who empower values and practices that are recognized by participants to be important aspects of physician identity.

Ageing perspective on cognitive outcomes from reproductive hormone adjustments.

In addition to primary reproductive functions, gonadal hormones play an important role in an array of neural mechanisms across the human lifespan. The ageing-related decline in their activity has been linked to the deterioration of cognitive functions in otherwise healthy women, associated with menopause transition, contributing to higher incidents of post-menopause dementia. Given the growing utility of gonadal steroids for birth control, as well as for compensatory treatment of menopause and oophorectomy symptoms, and adjuvant transgender therapy, their long-term effects on neural mechanisms warrant comprehensive assessment. In this article, we present an ageing perspective on the cognitive outcomes from contraceptive and replacement therapeutic use of gonadal hormones and discuss their effects on the risk of developing Alzheimer's and Parkinson's dementia. Despite rising data supporting the ameliorative effects of reproductive hormones on cognitive facilities, their impact varies depending on study design and type of intervention, thus, implying dynamic neuro-endocrine interactions with complex compensatory mechanisms. Elucidating differential effects of reproductive hormone adjustments on cognition with underlying mechanisms is expected not only to shed light on important aspects of brain ageing and dementia but to facilitate their use in personalized medicine with improved safety margins and therapeutic outcomes.

Non-selective dampening of the host immune response after hepatitis C clearance and its association with circulating chemokine and endotoxin levels.

BACKGROUND & AIMS: Direct-acting antiviral (DAA) therapy has revolutionized treatment for the hepatitis C virus (HCV). While DAA therapy is common, little is known about the intrahepatic immunological changes after sustained virologic response (SVR). We aim to describe transcriptional alterations of the gut microbiome and the liver after SVR. METHODS: Twenty-two HCV patients were evaluated before and 9 months after 12 weeks of sofosbuvir/velpatasvir treatment. All achieved SVR. A liver biopsy, portal blood (direct portal vein cannulation), peripheral blood and stool samples were obtained. RNA-seq and immunofluorescent staining were performed on liver biopsies. RNA-seq and 16S rRNA metagenomics were performed on stool. RESULTS: Differential expression within liver transcription showed 514 downregulated genes (FDR q < .05; foldchange > 2) enriched in inflammatory pathways; of note, GO:0060337, type 1 IFN signalling (p = 8e-23) and GO:0042742, defence response to bacterium (p = 8e-3). Interestingly, microbial products increased in the portal blood and liver after SVR. Due to the increase in microbial products, the gut microbiome was investigated. There was no dysbiosis by Shannon diversity index or Bacteroides/Firmicutes ratio. There was a differential increase in genes responsible for bacterial lipopolysaccharide production after SVR. CONCLUSIONS: The decrease in the antiviral interferon pathway expression was expected after SVR; however, there was an unanticipated decrease in the transcription of genes involved in recognition and response to bacteria, which was associated with increased levels of microbial products. Finally, the alterations in the function of the gut microbiome are a promising avenue for further investigation of the gut-liver axis, especially in the context of the significant immunological changes noted after SVR.

Assessment of essential surgical and anaesthesia care capacity: a cross-sectional study in five Pacific Island Countries.

Background: Pacific Island Countries (PICs) face unique challenges in providing surgical care. We assessed the surgical care capacity of five PICs to inform the development of National Surgical, Obstetric and Anaesthesia Plans (NSOAP). Methods: We conducted a cross-sectional survey of 26 facilities in Fiji, Tonga, Vanuatu, Cook Islands, and Palau using the World Health Organization - Program in Global Surgery and Social Change Surgical Assessment Tool. Findings: Eight referral and 18 first-level hospitals containing 39 functioning operating theatres, 41 post-anaesthesia care beds, and 44 intensive care unit beds served a population of 1,321,000 across the five countries. Most facilities had uninterrupted access to electricity, water, internet, and oxygen. However, CT was only available in 2/8 referral hospitals, MRI in 1/8, and timely blood transfusions in 4/8. The surgical, obstetric, and anaesthetist specialist density per 100,000 people was the highest in Palau (49.7), followed by Cook Islands (22.9), Tonga (9.9), Fiji (7.1), and Vanuatu (5.0). There were four radiologists and 3.5 pathologists across the five countries. Surgical volume per 100,000 people was the lowest in Vanuatu (860), followed by Fiji (2,247), Tonga (2,864), Cook Islands (6,747), and Palau (8,606). The in-hospital peri-operative mortality rate (POMR) was prospectively monitored in Tonga and Cook Islands but retrospectively measured in other countries. POMR was below 1% in all five countries. Interpretation: Whilst PICs share common challenges in providing specialised tertiary services, there is substantial diversity between the countries. Strategies to strengthen surgical systems should incorporate both local contextualisation within each PIC and regional collaboration between PICs. Funding: None.

Chondroitin 4-O-sulfation regulates hippocampal perineuronal nets and social memory.

Glycan alterations are associated with aging, neuropsychiatric, and neurodegenerative diseases, although the contributions of specific glycan structures to emotion and cognitive functions remain largely unknown. Here, we used a combination of chemistry and neurobiology to show that 4-O-sulfated chondroitin sulfate (CS) polysaccharides are critical regulators of perineuronal nets (PNNs) and synapse development in the mouse hippocampus, thereby affecting anxiety and cognitive abilities such as social memory. Brain-specific deletion of CS 4-O-sulfation in mice increased PNN densities in the area CA2 (cornu ammonis 2), leading to imbalanced excitatory-to-inhibitory synaptic ratios, reduced CREB activation, elevated anxiety, and social memory dysfunction. The impairments in PNN densities, CREB activity, and social memory were recapitulated by selective ablation of CS 4-O-sulfation in the CA2 region during adulthood. Notably, enzymatic pruning of the excess PNNs reduced anxiety levels and restored social memory, while chemical manipulation of CS 4-O-sulfation levels reversibly modulated PNN densities surrounding hippocampal neurons and the balance of excitatory and inhibitory synapses. These findings reveal key roles for CS 4-O-sulfation in adult brain plasticity, social memory, and anxiety regulation, and they suggest that targeting CS 4-O-sulfation may represent a strategy to address neuropsychiatric and neurodegenerative diseases associated with social cognitive dysfunction.

Optimized vitamin D repletion with oral thin film cholecalciferol in patients undergoing stem cell transplant.

Vitamin D deficiency is common in childhood, pervasive before and after bone marrow transplant, and is associated with increased incidence of graft-versus-host disease (GVHD) and decreased survival in patients undergoing hematopoietic stem cell transplant (HSCT). Numerous barriers impede replacement, including malabsorption secondary to gut GVHD, mucositis, inability to take capsules, kidney disease, liver disease, and infection; many patients remain refractory despite vitamin D therapy. We hypothesized that a different formulation of cholecalciferol, administered on the tongue as a readily dissolving oral thin film (OTF), would ease administration and facilitate therapeutic vitamin D levels (>35 ng/mL) in patients who are refractory. In this prospective pilot study, we evaluated 20 patients after HSCT (range, day +21 - day +428 at enrollment) with serum vitamin D levels ≤35 ng/mL. Cholecalciferol OTF strips were administered for 12 weeks. Dosing was based on patient body weight and titrated per individual pharmacokinetics. Wilcoxon matched-pairs signed-rank test demonstrated marked improvement in all 20 patients who were formerly refractory, increasing from a median baseline vitamin D level of 29.2 ng/mL to 58 ng/mL at end of study (P < .0001). All patients demonstrated improvement in serum vitamin D level by week 4 on study, some of whom had been refractory for years prior. Median dose was 1 OTF strip (40 000 IU) per week. No toxicity was observed. This formulation proved to be safe, effective, efficient, and well received. We are eager to explore other patient populations, which might benefit from this promising development, and other therapeutics that might be optimized using this mode of delivery. This trial was registered at www.clinicaltrials.gov as #NCT04818957.

What Should I Know About Hormones for Symptoms of Menopause?

This JAMA Internal Medicine Patient Page describes hormone therapy to treat the symptoms of menopause.

What Should I Know About Stopping Routine Cancer Screening?

This JAMA Internal Medicine Patient Page describes benefits and harms of cancer screening and how to decide when it may be time to stop routine screening.

Alcohol treatment discussions and clinical outcomes among patients with alcohol-related cirrhosis.

BACKGROUND: Alcohol cessation is the cornerstone of treatment for alcohol-related cirrhosis. This study evaluated associations between medical conversations about alcohol use disorder (AUD) treatment, AUD treatment engagement, and mortality. METHODS: This retrospective cohort study included all patients with ICD-10 diagnosis codes for cirrhosis and AUD who were engaged in hepatology care in a single healthcare system in 2015. Baseline demographic, medical, liver disease, and AUD treatment data were assessed. AUD treatment discussions and initiation, alcohol cessation, and subsequent 5-year mortality were collected. Multivariable models were used to assess the factors associated with subsequent AUD treatment and 5-year mortality. RESULTS: Among 436 patients with cirrhosis due to alcohol, 65 patients (15%) received AUD treatment at baseline, including 48 (11%) receiving behavioral therapy alone, 11 (2%) receiving pharmacotherapy alone, and 6 (1%) receiving both. Over the first year after a baseline hepatology visit, 37 patients engaged in AUD treatment, 51 were retained in treatment, and 14 stopped treatment. Thirty percent of patients had hepatology-documented AUD treatment recommendations and 26% had primary care-documented AUD treatment recommendations. Most hepatology (86%) and primary care (88%) recommendations discussed behavioral therapy alone. Among patients with ongoing alcohol use at baseline, AUD treatment one year later was significantly, independently associated with AUD treatment discussions with hepatology (adjusted odds ratio (aOR): 3.23, 95% confidence interval (CI): 1.58, 6.89) or primary care (aOR: 2.95; 95% CI: 1.44, 6.15) and negatively associated with having Medicaid insurance (aOR: 0.43, 95% CI: 0.18, 0.93). When treatment was discussed in both settings, high rates of treatment ensued (aOR: 10.72, 95% CI: 3.89, 33.52). Over a 5-year follow-up period, 152 (35%) patients died. Ongoing alcohol use, age, hepatic decompensation, and hepatocellular carcinoma were significantly associated with mortality in the final survival model. CONCLUSION: AUD treatment discussions were documented in less than half of hepatology and primary care encounters in patients with alcohol-related cirrhosis, though such discussions were significantly associated with receipt of AUD treatment.