Conformation Controlled Hydrogelation of Minimalistic α, γ Hybrid Peptide.

A majority of short peptide (≤7 amino acids) hydrogels are primarily assembled via cross ß-structure formation. In contrast to the natural trend, herein, we report the formation of supramolecular hydrogel from the ultrashort hybrid folded peptide composed of canonical α-amino acid and noncanonical γ-amino acid, Fmoc-γPhe-Phe-OH. The designed hybrid peptide hydrogel is composed of entangled fibers, has viscoelastic properties, exhibits proteolytic stability, and exhibits cytocompatibility with L929 fibroblast cells. Mutating the peptide sequence by altering the position of γPhe from the N-termini to C-termini transforms the self-assembly into crystalline aggregates. Combining FTIR, 2D NMR, and DFT calculations revealed that the hydrogel-forming peptide adopts a C9 H-bonded conformation, resembling the well-known γ-turn. However, the isomeric hybrid peptide adopts an extended structure. The present study highlights the importance of secondary structure in the higher order assembly of minimalist hybrid peptides and broadens the range of secondary structures to design short peptide-based hydrogels.

High-throughput quantitative assessments of the chemical complementarity of celiac disease related IGH CDR3s and a gliadin epitope.

The long-term value of efficient antigen discovery includes gaining insights into the variety of potential cancer neoantigens, effective vaccines lacking adverse effects, and adaptive immune receptor (IR) targets for blocking adaptive IR-antigen interactions in autoimmunity. While the preceding goals have been partially addressed via big data approaches to HLA-epitope binding, there has been little such progress in the big data setting for adaptive IR-epitope binding. This delay in progress for the latter is likely due to, among other things, the much more complicated adaptive IR repertoire in an individual compared to individual HLA alleles. Thus, results described here represent the application of an algorithm for efficient assessment of IGH CDR3-gliadin epitope interactions, with a focus on epitopes known to be associated with an immune response in celiac disease. The hydrophobic, chemical complementarity between celiac case IGH CDR3s and known celiac epitopes was found to be greater in comparison to the hydrophobic, chemical complementarity between the same celiac case IGH CDR3s and a series of control epitopes. Thus, the approaches indicated here likely offer guidance for the development of conveniently applied algorithms for antigen verification and discovery.

Spontaneous thrombosis and calcification of giant cavernous carotid artery aneurysm: A rare case and management insights.

Background: Giant cavernous carotid artery aneurysms (>25 mm) are rare (3-5%), with some prone to spontaneous thrombosis (10-20% complete). We present a unique case of one of the largest aneurysms spontaneously thrombosing and calcifying. Case Description: A 57-year-old with persistent right-sided headaches had a substantial hyperdense mass in the right middle cranial fossa, eroding petrous bone. Magnetic resonance imaging and digital subtraction angiography revealed a giant cavernous segment fusiform aneurysm of the right internal carotid artery (ICA) with spontaneous thrombosis and distal ICA occlusion. Collateral circulation maintains the cerebral blood supply. Despite anatomical challenges, conservative management was chosen due to the patient's stability. Conclusion: This case highlights the complex interplay between thrombosed giant aneurysms and affected vessels, with unique features such as cross-flow, calcification, and bone erosion. We advocate conservative management for stable cases, supported by literature, emphasizing vigilant follow-up. This expands the spectrum of aneurysm presentations and encourages further research into their dynamics.

Peptide hydrogen-bonded organic frameworks.

Hydrogen-bonded porous frameworks (HPFs) are versatile porous crystalline frameworks with diverse applications. However, designing chiral assemblies or biocompatible materials poses significant challenges. Peptide-based hydrogen-bonded porous frameworks (P-HPFs) are an exciting alternative to conventional HPFs due to their intrinsic chirality, tunability, biocompatibility, and structural diversity. Flexible, ultra-short peptide-based P-HPFs (composed of 3 or fewer amino acids) exhibit adaptable porous topologies that can accommodate a variety of guest molecules and capture hazardous greenhouse gases. Longer, folded peptides present challenges and opportunities in designing P-HPFs. This review highlights recent developments in P-HPFs using ultra-short peptides, folded peptides, and foldamers, showcasing their utility for gas storage, chiral recognition, chiral separation, and medical applications. It also addresses design challenges and future directions in the field.

The Next Horizon of Drug Development: External Control Arms and Innovative Tools to Enrich Clinical Trial Data.

Conducting clinical trials (CTs) has become increasingly costly and complex in terms of designing and operationalizing. These challenges exist in running CTs on novel therapies, particularly in oncology and rare diseases, where CTs increasingly target narrower patient groups. In this study, we describe external control arms (ECA) and other relevant tools, such as virtualization and decentralized clinical trials (DCTs), and the ability to follow the clinical trial subjects in the real world using tokenization. ECAs are typically constructed by identifying appropriate external sources of data, then by cleaning and standardizing it to create an analysis-ready data file, and finally, by matching subjects in the external data with the subjects in the CT of interest. In addition, ECA tools also include subject-level meta-analysis and simulated subjects' data for analyses. By implementing the recent advances in digital health technologies and devices, virtualization, and DCTs, realigning of CTs from site-centric designs to virtual, decentralized, and patient-centric designs can be done, which reduces the patient burden to participate in the CTs and encourages diversity. Tokenization technology allows linking the CT data with real-world data (RWD), creating more comprehensive and longitudinal outcome measures. These tools provide robust ways to enrich the CT data for informed decision-making, reduce the burden on subjects and costs of trial operations, and augment the insights gained for the CT data.

OA-GAN: organ-aware generative adversarial network for synthesizing contrast-enhanced medical images.

Contrast-enhanced computed tomography (CE-CT) images are vital for clinical diagnosis of focal liver lesions (FLLs). However, the use of CE-CT images imposes a significant burden on patients due to the injection of contrast agents and extended shooting. Deep learning-based image synthesis models offer a promising solution that synthesizes CE-CT images from non-contrasted CT (NC-CT) images. Unlike natural images, medical image synthesis requires a specific focus on certain organs or localized regions to ensure accurate diagnosis. Determining how to effectively emphasize target organs poses a challenging issue in medical image synthesis. To solve this challenge, we present a novel CE-CT image synthesis model called, Organ-Aware Generative Adversarial Network (OA-GAN). The OA-GAN comprises an organ-aware (OA) network and a dual decoder-based generator. First, the OA network learns the most discriminative spatial features about the target organ (i.e. liver) by utilizing the ground truth organ mask as localization cues. Subsequently, NC-CT image and captured feature are fed into the dual decoder-based generator, which employs a local and global decoder network to simultaneously synthesize the organ and entire CECT image. Moreover, the semantic information extracted from the local decoder is transferred to the global decoder to facilitate better reconstruction of the organ in entire CE-CT image. The qualitative and quantitative evaluation on a CE-CT dataset demonstrates that the OA-GAN outperforms state-of-the-art approaches for synthesizing two types of CE-CT images such as arterial phase and portal venous phase. Additionally, subjective evaluations by expert radiologists and a deep learning-based FLLs classification also affirm that CE-CT images synthesized from the OA-GAN exhibit a remarkable resemblance to real CE-CT images.

Metal-driven folding and assembly of a minimal ß-sheet into a 3D-porous honeycomb framework.

In contrast to short helical peptides, constrained peptides, and foldamers, the design and fabrication of crystalline 3D frameworks from the ß-sheet peptides are rare because of their high self-aggregation propensity to form 1D architectures. Herein, we demonstrate the formation of a 3D porous honeycomb framework through the silver coordination of a minimal ß-sheet forming a peptide having terminal metal coordinated 4- and 3-pyridyl ligands.

Navigating Uncharted Waters: Comparative Analysis of Clinical Progression and Outcomes in Vestibular Schwannoma Patients with Papilledema and without Hydrocephalus, Versus Those without Papilledema and Hydrocephalus: A Comprehensive Institutional Insight.

BACKGROUND: Papilledema's association with hydrocephalus (HCP)-linked larger vestibular schwannoma (VS) is established but cases lacking concurrent HCP require further investigation. METHODS: This retrospective comparative observational study, conducted from July 2018 to July 2023, examined 120 VS patients undergoing surgery. Patients were categorized into Group 1 (papilledema without HCP) and Group 2 (no papilledema or HCP), with comprehensive data analyzed. RESULTS: In this study, Group 1 (14 patients with papilledema) and Group 2 (106 patients without papilledema or HCP) were compared. Group 1 was younger (mean age 27.21 ± 11.73 years) than Group 2 (mean age 54.66 ± 11.44 years). Both groups had similar symptom durations and tumor detection times. Group 1 had increased vascularity (P = 0.001), elevated cisterna magna protein levels (P = 0.001), and a higher incidence of neurofibromatosis 2 (P = 0.003). They also experienced longer surgeries (P = 0.001) and more blood loss (P = 0.001), leading to extended postoperative complications. Group 2 showed improved postsurgery visual outcomes (P = 0.001), better Glasgow Outcome Scores (P = 0.001), enhanced facial nerve preservation (P = 0.002), and improved hearing on follow-up (P = 0.003). Logistic regression analysis highlighted prolonged surgery duration (P = 0.057) and papilledema (P = 0.0001) as significant factors influencing visual improvement. CONCLUSIONS: Patients with VS require preoperative fundoscopy evaluation due to potential visual loss and papilledema, even without HCP. Early treatment initiation enhances visual and hearing outcomes. Meticulous surgery is vital given the lesion's hypervascular nature and adherence to surrounding structures. Preoperative embolization may aid in preserving neurovascular structures. In developing countries with higher blindness rates, judicious noncontrast computed tomography brain evaluation is crucial for timely detection and treatment initiation of lesions like VS.

Synthesis and mechanistic study of ultrashort peptides that inhibits Alzheimer's Aß-aggregation-induced neurotoxicity.

Misfolding/aggregation of ß-amyloid peptide lead to the formation of toxic oligomers or accumulation of amyloid plaques, which is a seminal step in the progression of Alzheimer's disease (AD). Despite continuous efforts in the development of therapeutic agents, the cure for AD remains a major challenge. Owing to specific binding affinity of structure-based peptides, we report the synthesis of new peptide-based inhibitors derived from the C-terminal sequences, Aß38-40 and Aß40-42. Preliminary screening using MTT cell viability assay and corroborative results from ThT fluorescence assay revealed a tripeptide showing significantly effective inhibition towards Aß1-42 aggregation and induced toxicity. Peptide 3 exhibited excellent cell viability of 94.3 % at 2 µM and of 100 % at 4 µM and 10 µM. CD study showed that peptide 3 restrict the conformation transition of Aß1-42 peptide towards cross-ß-sheet structure and electron microscopy validated the absence of Aß aggregates as indicated by the altered morphology of Aß1-42 in the presence of peptide 3. The HRMS-ESI, DLS and ANS studies were performed to gain mechanistic insights into the effect of inhibitor against Aß aggregation. This Aß-derived ultrashort motif provides impetus for the development of peptide-based anti-AD agents.

A comprehensive analysis of different types of clinical rounds in hospital medicine.

Table rounds and bedside rounds are two methods healthcare professionals employ during clinical rounds for patient care and medical education. Bedside rounds involve direct patient engagement and physical examination, thus significantly impacting patient outcomes, such as improving communication and patient satisfaction. Table rounds occur in a conference room without the patient present and involve discussing patient data, which is more effective in fostering structured medical education. Both bedside and table rounds have pros and cons, and healthcare professionals should consider the specific requirements of their patients and medical trainees when deciding which approach to use. This research utilized a comprehensive search to identify relevant resources, such as university website links, as well as a PubMed search using relevant keywords such as 'bedside rounding,' 'table rounding,' and 'patient satisfaction.' Relevance, publication date, and study design were the basis for inclusion criteria. This study compared the effectiveness of these two methods based on physician communication, medical education, patient care, and patient satisfaction.

Unsupervised Domain Adaptation Using Fourier Phase Enhanced Training Images for Liver Tumors Detection in Multi-phase CT Images.

Computer-aided diagnostic methods, such as automatic and precise liver tumor detection, have a significant impact on healthcare. In recent years, deep learning-based liver tumor detection methods in multi-phase computed tomography (CT) images have achieved noticeable performance. Deep learning frameworks require a substantial amount of annotated training data but obtaining enough training data with high quality annotations is a major issue in medical imaging. Additionally, deep learning frameworks experience domain shift problems when they are trained using one dataset (source domain) and applied to new test data (target domain). To address the lack of training data and domain shift issues in multiphase CT images, here, we present an adversarial learning-based strategy to mitigate the domain gap across different phases of multiphase CT scans. We introduce to use Fourier phase component of CT images in order to improve the semantic information and more reliably identify the tumor tissues. Our approach eliminates the requirement for distinct annotations for each phase of CT scans. The experiment results show that our proposed method performs noticeably better than conventional training and other methods.

Adaptive Graph Convolutional Networks for Medical Image Segmentation.

Medical image segmentation is very essential for computer-aided diagnosis in the field of medical imaging. In the last decade, Deep Learning-based frameworks (e.g., UNet) have been widely used in medical applications such as image segmentation tasks. Recently, numerous Transformer-based frameworks are presented for the image segmentation tasks as their design can utilize long-range dependencies. Transformer's design has a weak inductive bias since it does not take advantage of local relationships between pixels and lacks scale invariance. Consequently, Transformers require large datasets for convergence whereas the availability of massive medical datasets is challenging. In this paper, we present a graph-based approach replacing Transformer design to capture long-range dependencies and reduce computational cost. Our proposed framework achieves competitive performance using publicly available dataset Synapse.

Endovascular glue embolization of the medial posterior choroidal artery aneurysm: A case report and a literature review.

Background: The medial posterior choroidal artery (MPCA) aneurysm is extremely uncommon. Thus yet, just a few cases have been reported. Due to the deep position, narrow lumen, fragile walls, and extensive tortuosity, both endovascular and microsurgical procedures are strictly limited. A case study of successful endovascular glue embolization of a left MPCA aneurysm and a literature review is included in this report. Case Description: A 17-year-old female arrived at our institution 2 days after suffering a major intraventricular hemorrhage with a minor subarachnoid hemorrhage. Digital subtraction angiography revealed a left MPCA aneurysm. The patient underwent a successful endovascular glue embolization and had a favorable functional outcome. Conclusion: Endovascular glue embolization yielded favorable clinical and angiographic results in MPCA aneurysms where microcatheter access and maneuverability are challenging.

The yesterday, today and tomorrow of liver transplant.

With a very long history of setbacks and successes, organ transplantation is one of the greatest medical achievements of the twentieth century. Liver transplantation is currently the most effective method for treating end-stage liver disease. From humble beginnings, improvements in surgical technique, perioperative management, and immunosuppressive therapy have yielded excellent graft and patient outcomes. Most established 'liver transplant' (LT) centres have a 1-year survival rate exceeding 90%, and a 3-year survival rate of over 80%. With immense success, the need for hepatic grafts substantially exceeds their availability. This problem has been partially addressed by using split grafts, living donor liver transplantation (LDLT), and extended criteria grafts (ECG). This article reviews the immense progress made in various aspects of LT including evaluation, increasing donor pool, surgical advances, immunosuppression and anaesthesia related aspects and the way forward. With ongoing cutting edge research in technologies like artificial liver devices, tissue bioengineering and hepatocyte 'farms', the future of LT is more exciting than ever before.

Non-COVID-19 Cutaneous Mucormycosis from a Plastic Surgical Perspective.

Background Cutaneous mucormycosis is a rare and fulminant infection associated with high mortality. Plastic surgeons come across this infection in the settings of road traffic accidents, surgical site infections, and as a secondary infection with underlying bacterial soft tissue infections. Due to this infection's rarity and aggressive course, it is essential to initiate prompt multidisciplinary management at the first presentation. With this study, we aim to present a protocol for managing the condition. Methods This is a retrospective observational study of patients with cutaneous mucormycosis managed at a tertiary care hospital from January 1, 2016 to November 30, 2022 excluding patients with mucormycosis who tested positive for coronavirus disease 2019. Results Of 24 patients, 22 were males, and most were in the age group of 41 to 60 years. Sixteen patients survived and five out of eight deceased had comorbidities, six presented primarily without prior debridement, and six had trunk involvement. Conclusion A high index of clinical suspicion is necessary for early diagnosis and management of patients with invasive cutaneous mucormycosis. A multidisciplinary approach with appropriate medical and surgical management can improve outcomes in cases that otherwise carry a high mortality rate.

Pyrrole-thiazolidinone hybrids as a new structural class of broad-spectrum anti-infectives.

A series of pyrrole-thiazolidinone hybrids was designed, synthesized and evaluated for activities against ESKAP bacteria panel and mycobacterial pathogens. From the series, compound 9d showed prominent activity against S. aureus (MIC = 0.5 µg/mL) and compound 9k showed the most promising activity against M. tuberculosis H37Rv (MIC = 0.5 µg/mL). Potent derivatives were found to be non-toxic when tested against Vero cells. Compound 9d upon evaluation in vitro against several MRSA and VRSA strains produced activity comparable or better than standard drugs. In the anti-biofilm assay, 9d reduced S. aureus biofilm by >11% at 10x MIC. The dual inhibitory effect exhibited by pyrrole-thiazolidinone hybrids confirms their potential as new class of promising anti-infective agents.

A Boundary-Enhanced Liver Segmentation Network for Multi-Phase CT Images with Unsupervised Domain Adaptation.

Multi-phase computed tomography (CT) images have gained significant popularity in the diagnosis of hepatic disease. There are several challenges in the liver segmentation of multi-phase CT images. (1) Annotation: due to the distinct contrast enhancements observed in different phases (i.e., each phase is considered a different domain), annotating all phase images in multi-phase CT images for liver or tumor segmentation is a task that consumes substantial time and labor resources. (2) Poor contrast: some phase images may have poor contrast, making it difficult to distinguish the liver boundary. In this paper, we propose a boundary-enhanced liver segmentation network for multi-phase CT images with unsupervised domain adaptation. The first contribution is that we propose DD-UDA, a dual discriminator-based unsupervised domain adaptation, for liver segmentation on multi-phase images without multi-phase annotations, effectively tackling the annotation problem. To improve accuracy by reducing distribution differences between the source and target domains, we perform domain adaptation at two levels by employing two discriminators, one at the feature level and the other at the output level. The second contribution is that we introduce an additional boundary-enhanced decoder to the encoder-decoder backbone segmentation network to effectively recognize the boundary region, thereby addressing the problem of poor contrast. In our study, we employ the public LiTS dataset as the source domain and our private MPCT-FLLs dataset as the target domain. The experimental findings validate the efficacy of our proposed methods, producing substantially improved results when tested on each phase of the multi-phase CT image even without the multi-phase annotations. As evaluated on the MPCT-FLLs dataset, the existing baseline (UDA) method achieved IoU scores of 0.785, 0.796, and 0.772 for the PV, ART, and NC phases, respectively, while our proposed approach exhibited superior performance, surpassing both the baseline and other state-of-the-art methods. Notably, our method achieved remarkable IoU scores of 0.823, 0.811, and 0.800 for the PV, ART, and NC phases, respectively, emphasizing its effectiveness in achieving accurate image segmentation.

Tools to guide clinical discussions on physical activity, sedentary behaviour, and/or sleep for health promotion between primary care providers and adults accessing care: a scoping review.

BACKGROUND: Health care providers have reported low knowledge, skill, and confidence for discussing movement behaviours (i.e., physical activity, sedentary behaviour, and sleep), which may be improved with the use of tools to guide movement behaviour discussions in their practice. Past reviews have examined the psychometric properties, scoring, and behavioural outcomes of physical activity discussion tools. However, the features, perceptions, and effectiveness of discussion tools for physical activity, sedentary behaviour, and/or sleep have not yet been synthesized. The aim of this review was to report and appraise tools for movement behaviour discussions between health care providers and adults 18 + years in a primary care context within Canada or analogous countries. METHODS: An integrated knowledge translation approach guided this review, whereby a working group of experts in medicine, knowledge translation, communications, kinesiology, and health promotion was engaged from research question formation to interpretation of findings. Three search approaches were used (i.e., peer-reviewed, grey literature, and forward searches) to identify studies reporting on perceptions and/or effectiveness of tools for physical activity, sedentary behaviour, and/or sleep. The quality of included studies was assessed using the Mixed Methods Appraisal Tool. RESULTS: In total, 135 studies reporting on 61 tools (i.e., 51 on physical activity, one on sleep, and nine combining two movement behaviours) met inclusion criteria. Included tools served the purposes of assessment (n = 57), counselling (n = 50), prescription (n = 18), and/or referral (n = 12) of one or more movement behaviour. Most tools were used or intended for use by physicians, followed by nurses/nurse practitioners (n = 11), and adults accessing care (n = 10). Most tools were also used or intended to be used with adults without chronic conditions aged 18-64 years (n = 34), followed by adults with chronic conditions (n = 18). The quality of the 116 studies that evaluated tool effectiveness varied. CONCLUSIONS: Many tools were positively perceived and were deemed effective at enhancing knowledge of, confidence for, ability in, and frequency of movement behaviour discussions. Future tools should guide discussions of all movement behaviours in an integrated manner in line with the 24-Hour Movement Guidelines. Practically, this review offers seven evidence-based recommendations that may guide future tool development and implementation.

Direct Access to α,ß-Alkynylamides via Pd-Catalyzed Carbonylation of Terminal Alkynes with Amines Using Chloroform as the CO Surrogate.

We describe the first-time use of a palladium-di(1-adamantyl)-n-butylphosphine catalytic system for the synthesis of alk-2-ynamides from terminal alkynes via aminocarbonylation reaction. This method avoids the direct use of toxic CO gas by utilizing chloroform as an in situ CO source. The aminocarbonylation of both aromatic and aliphatic electron-rich alkyne nucleophiles is reported for the first time. The mild condition provides alk-2-ynamides within 50 min under microwave irradiation at 80 °C.

Sudden cardiac death in the adolescent population: a narrative review.

Background: Death from unexpected circulatory arrest within 60 min of onset of symptom is known as sudden cardiac death (SCD). In spite of the advancement in treatment and prevention strategies, SCD remains the most common cause of death worldwide especially in the young. Main body: This review focuses on highlighting how different cardiovascular diseases contribute to SCD. We discuss the clinical symptoms that the patient experience prior to sudden cardiac arrest and the treatment strategies including pharmacological and surgical treatment. Conclusions: We conclude that since there are many causes of SCD and very few treatment options, prevention strategies, early detection, and resuscitation of those at greatest risk is important.