A federated learning architecture for secure and private neuroimaging analysis.

The amount of biomedical data continues to grow rapidly. However, collecting data from multiple sites for joint analysis remains challenging due to security, privacy, and regulatory concerns. To overcome this challenge, we use federated learning, which enables distributed training of neural network models over multiple data sources without sharing data. Each site trains the neural network over its private data for some time and then shares the neural network parameters (i.e., weights and/or gradients) with a federation controller, which in turn aggregates the local models and sends the resulting community model back to each site, and the process repeats. Our federated learning architecture, MetisFL, provides strong security and privacy. First, sample data never leave a site. Second, neural network parameters are encrypted before transmission and the global neural model is computed under fully homomorphic encryption. Finally, we use information-theoretic methods to limit information leakage from the neural model to prevent a "curious" site from performing model inversion or membership attacks. We present a thorough evaluation of the performance of secure, private federated learning in neuroimaging tasks, including for predicting Alzheimer's disease and for brain age gap estimation (BrainAGE) from magnetic resonance imaging (MRI) studies in challenging, heterogeneous federated environments where sites have different amounts of data and statistical distributions.

Transcatheter Patent Ductus Arteriosus Closure in Premature Infants: Comparison of Echocardiogram and Angiogram Measurements.

Transcatheter patent ductus arteriosus (PDA) closure (TCPC) utilizing transthoracic echocardiogram (TTE) as the sole imaging guide could simplify care. This single-center study compares PDA dimensions obtained from the TTE and angiogram images of patients who underwent attempted TCPC at Stead Family Children's Hospital from 10/01/2019 to 10/31/2020. Blinded investigators measured these dimensions solely for this study and had no impact on clinical care. Also, a hypothetical Piccolo device size was chosen based on the TTE dimensions and another on the angiographic dimensions, and then the correlation was analyzed. Sixty-two patients underwent TCPC attempts. TTE tends to overestimate the PDA narrowest dimension and underestimate the PDA length and aortic end dimension. Linear regression analysis revealed a weak correlation between the length and aortic diameter (R = 0.37 and 0.21, respectively). A modest correlation was observed for the smallest dimension without color Doppler (R = 0.57) and with color Doppler, which was utilized when needed (R = 0.6). Bland-Altman analysis revealed a smaller mean difference between the TTE and angiogram measurements of the narrowest diameter without color Doppler (0.4 mm) and with color Doppler (used as needed) (0.4 mm). However, the mean difference is larger for the aortic end (- 1.64 mm) and the length (- 1.73 mm). TTE accurately predicted the Piccolo device size in 43 (72%) patients and overestimated the size in 17 (28%) patients to the next size. Our findings should be verified with further studies, and additional development of protocols is needed to use TTE to guide TCPC without fluoroscopy.

Fetal left and right ventricular strain parameters using speckle tracking in congenital heart diseases.

Assessment of fetal ventricular function is mostly subjective, and currently, for the objective assessment left ventricular shortening fraction is obtained. However, this by itself is not very reliable. Hence, more tools that can provide an objective assessment are needed to increase the confidence of functional assessment. Speckle tracking imaging can provide one such tool. In this study we sought to establish the normative value of global longitudinal and circumferential strain for our fetal patients and for two major forms of congenital heart diseases, namely atrioventricular canal defects (AVC) and uncorrected dextro-transposition of the great arteries (dTGA) to act as a benchmark. The study was completed via a single center retrospective analysis on 72 fetal echocardiograms (26 normal, 15 dTGA, and 31 AVC). Tomtec Arena™ echocardiography analysis software was used for analysis. In normal fetuses, mean left ventricular (LV) global longitudinal strain (GLS) was - 22.6% (95% CI -24, -21.1) and mean right ventricular (RV) GLS was - 22.1% (95% CI -23.6, -20.6). In AVC patients LV GLS was-26.6% (95% CI -28,-25.3) and mean RV GLS was - 26.5% (95% CI -27.9,-25.2). In dTGA patients LV GLS was - 22.9% (95% CI of -24.8, -21) and RV GLS was - 21.3% (95% CI was - 23.4, -20.8). There was good intra-rater reliability though poor to fair inter-rater reliability. Notwithstanding its current limitations, strain imaging can provide useful information that can increase confidence of cardiac functional assessment in fetal patients. However, to be reliable across the board, further automation and standardization is required.

Pulmonary tuberculosis in an adult presenting with severe hyponatremia: A case report and review of literature.

Key Clinical Message: Identifying pulmonary pathology while evaluating electrolyte disorders is crucial for optimal patient management. Physicians working in endemic regions of tuberculosis should consider this pathology as a differential for electrolyte imbalances. Abstract: Hyponatremia, a common electrolyte imbalance, can arise from various underlying etiologies such as diuretics, diarrhea, vomiting, congestive heart failure, and liver and renal disease. We present a case report of a 74-year-old man highlighting the association between pulmonary tuberculosis (TB) and the development of hyponatremia. GeneXpert assay of the patient's sputum sample led to the identification of underlying active pulmonary TB as the cause of hyponatremia. The patient was started on anti-TB therapy, and concurrent fluid restriction and sodium supplementation were initiated to correct the electrolyte imbalance. Over the next 3 days, the patient demonstrated clinical improvement with the resolution of hyponatremia. This case also highlights the importance of considering TB as a potential etiology in patients presenting with hyponatremia, especially in endemic areas. Further research is warranted to explore the mechanistic pathways linking pulmonary TB and hyponatremia, aiding in the development of targeted therapeutic interventions.

Brugada syndrome unmasked by dengue fever.

Key Clinical Message: Understanding the circumstances, leading to unmasking of hidden Brugada syndrome is essential for the practicing clinician and the patients so that they are informed adequately to seek prompt medical attention. Abstract: Brugada syndrome is a genetic arrhythmia syndrome characterized by a coved type of ST-segment elevation in the ECG. The patients are usually asymptomatic, with unmasking of the disease under certain conditions. We are reporting the case of a patient diagnosed with Brugada syndrome, which was unmasked during an attack of dengue fever.

A rare case of intra-parenchymal meningioma in a female patient who presented with seizures: A case report.

Key Clinical Message: Meningiomas are slow-growing tumors that develop from the arachnoid cap cells' meningothelial cells. Males are more likely to develop intra-parenchymal meningiomas, which also manifest earlier than ordinary meningiomas and are uncommon. Abstract: Meningiomas are slow-growing neoplasms which arise from the meningothelial cells of the arachnoid cap cells. Unlike other meningiomas, intra-parenchymal meningiomas do not originate from dura. Intra-parenchymal meningiomas are more common in males and develop earlier than regular meningiomas. Because of the rare occurrence the intra-parenchymal meningiomas, they are commonly misdiagnosed.

A rare extrapulmonary manifestation of tuberculosis in a chronic kidney disease patient.

Key Clinical Message: Chronic kidney disease (CKD) and tuberculoma are two distinct medical conditions. Nonetheless, they can be related in very rare cases. The purpose of this case report is to consider screening tests such as IGRA (interferon gamma release assay) and TST (tuberculin skin test), for tuberculosis in CKD patients with a risk of infection, thereby increasing the awareness of tuberculoma in CKD and ensuring early treatment which would eventually decrease the morbidity and mortality rates in such patients. Abstract: Chronic kidney disease (CKD) associated with tuberculoma represents one of the rarest conditions occurring worldwide. Among tuberculous patients, only 1% show central nervous system involvement. We present a case of a 45-year-old male with CKD who presented with a seizure and was diagnosed to have tuberculoma.

A case of trichotillomania and bulimia nervosa in a patient with adult-onset attention-deficit/hyperactivity disorder (ADHD).

Key Clinical Message: Identifying any potential comorbidity such as bulimia nervosa (BN) and ADHD in trichotillomania patients is essential for a thorough treatment plan. Combining a multidisciplinary approach was found to be feasible and effective in the treatment. Abstract: Trichotillomania is frequently considered an isolated disorder; nevertheless, emerging evidence suggests that other psychiatric conditions, including obsessive-compulsive disorder (OCD), eating disorders, and attention-deficit/hyperactivity disorder (ADHD), are often found to coexist. Several studies showed that eating disorders, such as bulimia nervosa, were found in chronic hair-pullers, while OCD was considered a factor in predicting the prevalence of eating disorders, as well as the severity of trichotillomania in the populations. While the relationship between trichotillomania and OCD has been quite well-documented, the evidence of its association with bulimia nervosa and ADHD remains limited. Here, we report a case of trichotillomania with comorbid bulimia nervosa, major depressive disorder, and ADHD.

Toxic fasciculations-An unusual presentation of organophosphate poisoning.

The nicotinic symptom in Organo-Phosphate (OP) poisoning is an unusual presentation in an adult, as in our case of a 38-year-old man who also experienced decreased motor power of all limbs and diffuses fasciculation of the tongue and lower limbs.

Stars from the bones-An uncommon presentation of fat embolism syndrome.

Trauma or surgery to the lower limbs can cause fat from the marrow within the leg bones to enter the bloodstream and form an embolus. However, if there is cerebral involvement without any pulmonary or dermatological manifestations at diagnosis, it could delay identifying cerebral fat embolism (CFE).

Subcutaneous dirofilariasis in children-An emerging zoonotic nematodal infection: A case series.

Human subcutaneous dirofilariasis is an infection caused by filarial worms. Due to the recent rise of human disease, it is considered as an emerging zoonosis. Most of the cases in children recorded in India had ocular infection; very few subcutaneous cases of dirofilariasis have been reported in children.

A case of closedlip schizencephaly with absent septum pellucidum in an adult presenting with seizure disorder.

Key Clinical Message: To rule out underlying developmental brain defects such as schizencephaly, pediatric seizures necessitate a thorough examination. Adults who receive a diagnosis later in life may face severe management and prognosis difficulties. To avoid underdiagnosis of developing brain abnormalities, imaging should be a part of the workup for pediatric seizures. Imaging is critical to the diagnosis and therapy of such cases. Abstract: Closed-lip schizencephaly with the absence of the septum pellucidum is a rare congenital malformation of the brain that can be associated with a variety of neurological conditions. We report the case of a 25-year-old male with left hemiparesis who presented with recurrent seizures from childhood, poorly controlled with medications, and increased tremors. He has been taking anticonvulsant for the last 7 years and is under symptomatic management. Magnetic resonance imaging of the brain revealed closed-lip schizencephaly with absent septum pellucidum.

A case of vagal cephalgia as a manifestation of a lung neoplasm-A case report and review of literature.

Lung cancer can present with unilateral atypical facial pain, a rare symptom due to vagus nerve involvement or paraneoplastic syndrome. This manifestation is usually missed, delaying the diagnosis and prognosis. We discuss a case of a 45-year-old male who presented with right-sided hemifacial pain and with normal neurological investigations.

Takayasu arteritis in peripartum period-A clinical paradox.

Takayasu arteritis is a primary systemic vasculitides occurring among women in the childbearing age group. This interaction between TA and pregnancy is an area of interest that has to be addressed. Preconception and antepartum management of arterial hypertension and TAK disease activity is important to improve maternal and fetal outcomes.

Transferring Models Trained on Natural Images to 3D MRI via Position Encoded Slice Models.

Transfer learning has remarkably improved computer vision. These advances also promise improvements in neuroimaging, where training set sizes are often small. However, various difficulties arise in directly applying models pretrained on natural images to radiologic images, such as MRIs. In particular, a mismatch in the input space (2D images vs. 3D MRIs) restricts the direct transfer of models, often forcing us to consider only a few MRI slices as input. To this end, we leverage the 2D-Slice-CNN architecture of Gupta et al. (2021), which embeds all the MRI slices with 2D encoders (neural networks that take 2D image input) and combines them via permutation-invariant layers. With the insight that the pretrained model can serve as the 2D encoder, we initialize the 2D encoder with ImageNet pretrained weights that outperform those initialized and trained from scratch on two neuroimaging tasks -- brain age prediction on the UK Biobank dataset and Alzheimer's disease detection on the ADNI dataset. Further, we improve the modeling capabilities of 2D-Slice models by incorporating spatial information through position embeddings, which can improve the performance in some cases.

PROMETHEUS: Long-Term Exacerbation and Mortality Benefits of Implementing Single-Inhaler Triple Therapy in the US COPD Population.

Background: The US population includes 24 million to 29 million people with diagnosed and undiagnosed chronic obstructive pulmonary disease (COPD). Studies have demonstrated the safety and efficacy of single-inhaler triple therapy (SITT) in reducing COPD exacerbations. Long-term population implications of SITT use have not been quantified. Objectives: This simulation-based projection aimed to estimate the potential impact of widespread SITT use on the US COPD population. Methods: Exacerbation and all-cause mortality reductions reported in the Efficacy and Safety of Triple Therapy in Obstructive Lung Disease trial (ETHOS; NCT02465567) were used to project clinical outcomes in US patients meeting ETHOS trial eligibility criteria (ETHOS-Eligible) and patients meeting a practical definition of SITT eligibility (Expanded ETHOS-Eligible). The US COPD population was modeled with 1000 simulations of patient progression over 10 years. Agent characteristics were based on literature and claims analysis of the 2016-2018 Medicare 100% fee-for-service and IBM MarketScan® databases. Agent annual characteristics reflected incident cases, changes in COPD severity, treatment, mortality, and exacerbations under status quo treatment patterns and scenarios for the adoption of SITT. The scenarios assumed the reduced exacerbation and mortality rates associated with SITT according to ETHOS trial outcomes mean values. Results: Higher than current SITT adoption over 10 years would be expected to substantially reduce COPD exacerbation-associated hospitalizations by 2 million. Applying mean improvements reported in ETHOS for SITT would extend average patient life expectancy 2.2 years for ETHOS-Eligible patients and 1.7 years for Expanded ETHOS-Eligible patients. The number needed to treat to extend the average patient life by 1 year was 8 for the ETHOS-Eligible population and 10 for the Expanded ETHOS-Eligible population. Discussion: Widespread SITT adoption may be impeded by competitive pressures from generic treatments and nonadherence, and efficacy observed in clinical trials may not occur in real-world populations. Conclusions: Assuming ETHOS treatment effects and adherence translate to clinical practice, higher than current use of SITT can substantially reduce COPD exacerbations and hospitalizations and extend survival. These results should be viewed cautiously, because the improved outcomes for SITT in the ETHOS final retrieved vital statistics data were not statistically significant for all comparator therapy groups.

Zn2+-Induced Conformational Change Affects the SAM Binding in a Mycobacterial SAM-Dependent Methyltransferase.

Zinc is a cofactor for enzymes involved in DNA replication, peptidoglycan hydrolysis, and pH maintenance, in addition to the transfer of the methyl group to thiols. Here, we discovered a new role of Zn2+ as an inhibitor for S-adenosyl methionine (SAM) binding in a mycobacterial methyltransferase. Rv1377c is annotated as a putative methyltransferase that is upregulated upon the mitomycin C treatment of Mycobacterium tuberculosis. Sequence analysis and experimental validation allowed the identification of distinct motifs responsible for SAM binding. A detailed analysis of the AlphaFold-predicted structure of Rv1377c revealed four cysteine residues capable of coordinating a Zn2+ ion located in proximity to the SAM-binding site. Further, experimental studies showed distinct conformational changes upon Zn2+ binding to the protein, which compromised its ability to bind SAM. This is the first report wherein Zn2+-driven conformational changes in a methyltransferase undermines its ability to bind SAM.

Nitroisobenzofuranone, a small molecule inhibitor of multidrug-resistant Staphylococcus aureus, targets peptidoglycan biosynthesis.

Antimicrobial resistance (AMR) is a global health concern. Targetting AMR, we present an in situ lactonization mechanism generating 4-nitroisobenzofuran-1(3H)-one (IITK2020), an exclusive S. aureus inhibitor at 2-4 µg mL-1 MIC including multidrug-resistant S. aureus clinical strains, that prevents peptidoglycan biosynthesis.

Facial Palsy in COVID-19 Patient: A Case Report.

Facial paralysis is one of the common problems leading to facial deformation. COVID-19 virus rarely has been shown to be associated with facial palsy. Here we present a case of a 60-year-old woman who presented with features of left lower motor facial palsy signs along with common features suggestive of COVID-19 infection. Brain imaging did not reveal any pertinent pathology but her polymerase chain reaction for COVID-19 was positive. This case highlights the fact that acute COVID-19 infection can be considered a cause of motor neuron facial palsy in the ongoing pandemic of COVID-19. Cases with neurological features suggestive of facial palsy therefore should be suspected of acute COVID-19 infection based on other pertinent findings of COVID-19 infection and thus polymerase chain reaction testing should be done. Keywords: case reports; COVID-19; facial palsy.