Site-selective photo-crosslinking for the characterisation of transient ubiquitin-like protein-protein interactions.

Non-covalent protein-protein interactions are one of the most fundamental building blocks in cellular signalling pathways. Despite this, they have been historically hard to identify using conventional methods due to their often weak and transient nature. Using genetic code expansion and incorporation of commercially available unnatural amino acids, we have developed a highly accessible method whereby interactions between biotinylated ubiquitin-like protein (UBL) probes and their binding partners can be stabilised using ultraviolet (UV) light-induced crosslinks.

Comprehensive guide for epigenetics and transcriptomics data quality control.

Host response to environmental exposures such as pathogens and chemicals can include modifications to the epigenome and transcriptome. Improved signature discovery, including the identification of the agent and timing of exposure, has been enabled by advancements in assaying techniques to detect RNA expression, DNA base modifications, histone modifications, and chromatin accessibility. The interrogation of the epigenome and transcriptome cascade requires analyzing disparate datasets from multiple assay types, often at single-cell resolution, derived from the same biospecimen.

Respiratory syncytial virus vaccination in older adults and patients with chronic disorders: A position paper from the Portuguese Society of Pulmonology, the Portuguese Association of General and Family Medicine, the Portuguese Society of Cardiology, the Portuguese Society of Infectious Diseases and Clinical Microbiology, the Portuguese Society of Endocrinology, Diabetes and Metabolism, and the Portuguese Society of Internal Medicine.

Background: Respiratory syncytial virus (RSV) is an important cause of lower respiratory tract infection, hospitalisation and death in adults.

Methods: Based on evidence regarding the impact of RSV on adult populations at risk for severe infection and the efficacy and safety of RSV vaccines, the Portuguese Society of Pulmonology, the Portuguese Association of General and Family Medicine, the Portuguese Society of Cardiology, the Portuguese Society of Infectious Diseases and Clinical Microbiology, the Portuguese Society of Endocrinology, Diabetes and Metabolism, and the Portuguese Society of Internal Medicine endorses this position paper with recommendations to prevent RSV-associated disease and its complications in adults through vaccination.

Conclusion: The RSV vaccine is recommended for people aged ≥50 years with risk factors (chronic obstructive pulmonary disease, asthma, heart failure, coronary artery disease, diabetes, chronic kidney disease, chronic liver disease, immunocompromise, frailty, dementia, and residence in a nursing home) and all persons aged ≥60 years.

White matter connections within the central sulcus subserving the somato-cognitive action network.

The somato-cognitive action network (SCAN) consists of three nodes interspersed within Penfield's motor effector regions. The configuration of the somato-cognitive action network nodes resembles the one of the 'plis de passage' of the central sulcus: small gyri bridging the precentral and postcentral gyri. Thus, we hypothesize that these may provide a structural substrate of the somato-cognitive action network.

Isopropylmalate synthase regulatory domain removal abolishes feedback regulation at the expense of leucine homeostasis in plants.

In the leucine (Leu) biosynthesis pathway, homeostasis is achieved through a feedback regulatory mechanism facilitated by the binding of the end-product Leu at the C-terminal regulatory domain of the first committed enzyme, isopropylmalate synthase (IPMS). In vitro studies have shown that removing the regulatory domain abolishes the feedback regulation on plant IPMS while retaining its catalytic activity. However, the physiological consequences and underlying molecular regulation on Leu flux upon removing the IPMS C-terminal domain remain to be explored in plants.

Effects of early palliative care intervention on medical resource use among end-of-life patients.

Background: In Taiwan, as the population ages, palliative care services (PCS) have expanded significantly to include comprehensive benefit plans for critically ill individuals, supported by reimbursements from the National Health Insurance program. However, incorporating palliative care into the medical management of these patients presents several challenges. We aim to evaluate the effects of palliative care interventions on medical resources in end-of-life scenarios, to promote earlier palliative care access and provide high-quality healthcare services for patients.

Receptor CDCP1 is a potential target for personalized imaging and treatment of poor outcome HER2+, triple negative and metastatic ER+/HER2- breast cancers.

Purpose: Receptor CUB-domain containing- protein 1 (CDCP1) was evaluated as a target for detection and treatment of breast cancer.

Experimental Design: CDCP1 expression was assessed immunohistochemically in tumors from 423 patients (119 triple-negative breast cancer (TNBC); 75 HER2+; 229 ER+/HER2- including 228 primary tumors, 229 lymph node and 47 distant metastases). Cell cytotoxicity induced in vitro by a CDCP1-targeting antibody-drug conjugate (ADC), consisting of the human/mouse chimeric antibody ch10D7 and the microtubule disruptor monomethyl auristatin E (MMAE), was quantified, including in combination with HER2-targeting ADC T-DM1.

The Johns Hopkins Hope at Hopkins Clinic: supporting the comprehensive needs of individuals with metastatic breast cancer.

Purpose: Individuals with metastatic breast cancer (MBC) may live with their disease for many years. We initiated the Johns Hopkins Hope at Hopkins Clinic to assess the needs and optimize the care of these patients.

Patients And Methods: Patients with MBC who agreed to participate in the Clinic in addition to usual care completed patient-reported outcome (PRO) surveys.

Emerging Frontiers in Colorectal Cancer Therapy: From Targeted Molecules to Immunomodulatory Breakthroughs and Cell-Based Approaches.

Colorectal cancer (CRC) is ranked as the second leading cause of cancer-related deaths globally, necessitating urgent advancements in therapeutic approaches. The emergence of groundbreaking therapies, including chimeric antigen receptor-T (CAR-T) cell therapies, oncolytic viruses, and immune checkpoint inhibitors, marks a transformative era in oncology. These innovative modalities, tailored to individual genetic and molecular profiles, hold the promise of significantly enhancing patient outcomes.

Novel Strategy of Antibody Affinity Maturation and Enhancement of Nucleolin-Mediated Antibody-Dependent Cellular Cytotoxicity Against Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a clinically aggressive subtype of breast cancer that remains an unmet medical need. Because TNBC cells do not express the most common markers of breast cancers, there is an active search for novel molecular targets in triple-negative tumors. Additionally, this subtype of breast cancer presents strong immunogenic characteristics which have been encouraging the development of immunotherapeutic approaches against the disease.

A One-Step Plasma Assisted Synthesis of Gold Nanoparticles and Simultaneous Linker-Free Conjugation with Nestin: An In Vitro Study of Cellular Toxicity.

We present a method for conjugating antigens to gold nanoparticles (GNPs) during their synthesis via gas plasma, eliminating the need for chemical linkers and significantly speeding up the process (taking only 15 min). This fast, linker-free method produces biocompatible and stable GNPs, with potential for immunotherapy applications, such as antigen and antibody conjugation and drug delivery. We demonstrate the conjugation of the antigen Nestin (NES), a tumor marker, to GNPs using two approaches.

Lipoic acid improves wound healing through its immunomodulatory and anti-inflammatory effects in a diabetic mouse model.

Objectives: Diabetes mellitus is a chronic disease that has become more prevalent worldwide because of lifestyle changes. It leads to serious complications, including increased atherosclerosis, protein glycosylation, endothelial dysfunction, and vascular denervation. These complications impair neovascularization and wound healing, resulting in delayed recovery from injuries and an elevated risk of infections.

Profiling signaling mediators for cell-cell interactions and communications with microfluidics-based single-cell analysis tools.

Cell-cell interactions and communication represent the fundamental cornerstone of cells' collaborative efforts in executing diverse biological processes. A profound understanding of how cells interface through various mediators is pivotal across a spectrum of biological systems. Recent strides in microfluidic technologies have significantly bolstered the precision and prowess in capturing and manipulating cells with exceptional spatial and temporal resolution.

Roads to remission: evolving treatment concepts in type 2 inflammatory diseases.

Unlabelled: Non-communicable diseases (NCDs) characterised by type 2 inflammation, including asthma, allergic rhinitis, chronic rhinosinusitis with nasal polyps, atopic dermatitis, food allergies and eosinophilic esophagitis, are increasing in prevalence worldwide. Currently, there is a major paradigm shift in the management of these diseases, towards the concept of disease modification and the treatment goal remission, regardless of severity and age. Remission as a treatment goal in chronic inflammatory NCDs was first introduced in rheumatoid arthritis, and then adopted in other non-type 2 inflammatory diseases.

ScRNA-seq unveils the functional characteristics of glioma-associated macrophages and the regulatory effects of chlorogenic acid on the immune microenvironment-a study based on mouse models and clinical practice.

Introduction: Glioma is the most common primary malignant brain tumor. Despite advances in surgical techniques and treatment regimens, the therapeutic effects of glioma remain unsatisfactory. Immunotherapy has brought new hope to glioma patients, but its therapeutic outcomes are limited by the immunosuppressive nature of the tumor microenvironment (TME).

Loss of increases type I interferon signalling and reduces pancreatic tumour growth by enhancing immune cell infiltration.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of cancer, and despite low incidence rates, it remains the sixth leading cause of cancer related deaths worldwide. Immunotherapy, which aims to enhance the immune system's ability to recognize and eliminate cancer cells, has emerged as a promising approach in the battle against PDAC. PARP7, a mono-ADP-ribosyltransferase, is a negative regulator of the type I interferon (IFN-I) pathway and has been reported to reduce anti-tumour immunity.

Lyme disease associated neurological and musculoskeletal symptoms: A systematic review and meta-analysis.

Background And Objective: Lyme disease, caused by , presents major health challenges worldwide, leading to serious neurological and musculoskeletal issues that impact patients' lives and healthcare systems. This systematic review and meta-analysis aim to determine the prevalence and link between Lyme disease and these complications, aiming to enhance clinical and public health approaches.

Methods: We systematically searched PubMed, EMBASE, and Web of Science up until April 01, 2024, to find studies reporting the prevalence and severity of neurological and musculoskeletal complications associated with Lyme disease.

The burden of cutaneous fungal infections in a tertiary care hospital in Pakistan.

Objective: In Pakistan, the real extent of fungal infection is unknown. Our objective was to estimate the burden of major fungal diseases here to emphasize their public health importance.

Methods: In this retrospective study, the medical records (January 2019 - December 2019) of 863 patients diagnosed with superficial fungal infection (SFI) were reviewed at the dermatology department of Aga Khan University Hospital (AKUH) Karachi.

Identifying targets for antibiotic stewardship interventions in pediatric patients in Punjab, Pakistan: point prevalence surveys using AWaRe guidance.

Introduction: Surveillance of antibiotic use is crucial for identifying targets for antibiotic stewardship programs (ASPs), particularly in pediatric populations within countries like Pakistan, where antimicrobial resistance (AMR) is escalating. This point prevalence survey (PPS) seeks to assess the patterns of antibiotic use in pediatric patients across Punjab, Pakistan, employing the WHO AWaRe classification to pinpoint targets for intervention and encourage rational antibiotic usage.

Methods: A PPS was conducted across 23 pediatric wards of 14 hospitals in the Punjab Province of Pakistan using the standardized Global-PPS methodology developed by the University of Antwerp.

A comprehensive review of challenges and opportunities for stem cell research in India.

Stem cell research is a major focus for scientific and medical communities worldwide due to the potential for stem cells to restore function lost due to disease, trauma, congenital abnormalities, and aging. Stem cells can repair, replace, or regenerate damaged cells, tissues, or organs, making them an important area of research in regenerative medicine. India is emerging as a prominent hub for the development of stem cell therapy (SCT), and it is important to assess the current state of stem cell research in India and the potential for advancement to promote stem cell-based therapy.

Shearinines U-Y, indole diterpenoids from an entomogenous fungus, sp.

Five new indole diterpenoids, shearinines U-Y (2-6), and the known compound 22,23-dehydro-shearinine A (1) were isolated from cultures of the entomogenous fungus sp. Their structures were elucidated primarily by NMR experiments. The absolute configurations of 2-6 were assigned by electronic circular dichroism calculations, respectively.

Conglomerated Imiquimod and Metronidazole Incorporated Biodegradable Nanofibrous Mats for Potential Therapy of Cervical Cancer.

Background: In clinical practice, imiquimod is used to treat Human Papillomavirus (HPV)-related lesions, such as condyloma and Cervical Intraepithelial Neoplasia (CIN). Metronidazole is the most commonly prescribed antibiotic for bacterial vaginosis. The study developed biodegradable imiquimod- and metronidazole-loaded nanofibrous mats and assessed their effectiveness for the topical treatment of cervical cancer, a type of HPV-related lesion.

Characterization of jamun () juice fortified with nanoemulsified vitamin D: and assessment of its nutraceutical value and anti-diabetic potential.

This study aimed to fortify Jamun () juice with vitamin D to address vitamin D deficiency and boost health. A nanoemulsion of vitamin D was fabricated using a low-temperature (4-20C) sonication method and incorporated into the juice. The vitamin D fortified jamun juice (VDFJJ) exhibited a total polyphenol content of 14.

Evaluating the Role of KRAS and NRAS 3' Untranslated Region Polymorphisms in Susceptibility and Clinical Features of Laryngeal Squamous Cell Carcinoma.

Laryngeal squamous cell cancer (LSCC) is one of the most common head and neck cancers in which genetic factors play an important role in its occurrence. This study investigated the association of and gene polymorphisms with the risk of LSCC. polymorphisms including rs712, rs61764370, rs8720, and rs9266, as well as NRAS rs14804, were compared in the patient group (n=120) and the control group (n=100).

A novel TERT variant associated with a telomere biology disorder and challenges in variant classification.

Telomere biology disorders (TBDs) are inherited conditions associated with multisystem manifestations. We describe clinical and functional characterisation of a novel TERT variant. Whole-genome sequencing was performed along with single length analysis ().