Macropinocytosis inhibition attenuates pro-fibrotic responses in lung fibroblasts and pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a devastating chronic lung disorder with limited treatment options. Macropinocytosis is one of the key cellular processes involved in nutrient consumption from the extracellular environment under stress conditions. Here, we studied the role of macropinocytosis in lung fibroblast activation and experimental pulmonary fibrosis.

Establishing the First Genetic Variant Registry for Breast and Ovarian Cancer in Colombia: Insights and Implications.

Background: Genetic insights from diverse populations are key to advancing cancer detection, treatment, and prevention. Unlike other Latin American countries, Colombia lacks a centralized registry for germline and somatic mutations in breast and ovarian cancer. This study describes the country's first national variant registry, and the occurrence of recurrent mutations and potential founder effects in Colombia.

A Comprehensive Study of Circulating Blood Linear RNA nominates and as novel causal genes and early-stage biomarkers for Parkinson's Disease.

We leveraged transcriptomic data from 4,343 participants from four independent datasets to robustly identify and annotate circulating PD-associated transcripts. We identified 296 differentially expressed transcripts, 28 of which were transcribed from known PD-associated loci. Further, we found a significant overlap between our findings and transcripts dysregulated in brain, as well as proteins differentially accumulated in CSF.

Characterization of Traumatic Brain Injury Using Imaging and Physiological Parameters: A Pilot Study.

Introduction: The study was a cross-sectional study aimed to obtain preliminary data to characterize traumatic brain injuries (TBIs) of Operation Iraqi Freedom/Operation Endurance Freedom (OIF/OEF) in a cohort of insular veterans using perfusion and molecular imaging, and physiologic parameters.

Materials And Methods: The size and location of TBI lesions of 6 veterans were evaluated by quantifying cerebral perfusion and metabolism using Tc99m ethyl-cysteinate dimer SPECT/CT and fluorine-18 fluorodeoxyglucos PET/CT, respectively. Somatosensory evoked potentials were collected, and quality of life was measured by assessing functional status, activities of daily living, and depression levels.

Osteoprotegerin is induced by transforming growth factor-beta 1 and regulates pro-fibrotic responses in human dermal fibroblasts.

Transforming growth factor-beta1 (TGF-β1) is known to play a key role in the progression of organ fibrosis. Here, we demonstrate that TGF-β1 induces osteoprotegerin (OPG) expression in human dermal fibroblasts (HDFs) at both protein and mRNA levels. OPG neutralization has led to attenuation of TGF-β1-mediated profibrotic effects in HDFs.

Circulating blood circular RNA in Parkinson's Disease; from involvement in pathology to diagnostic tools in at-risk individuals.

To identify circRNAs associated with Parkinson's disease (PD) we leveraged two of the largest publicly available studies with longitudinal clinical and blood transcriptomic data. We performed a cross-sectional study utilizing the last visit of each participant (N = 1848), and a longitudinal analysis that included 1166 participants with at least two time points. We identified 192 differentially expressed circRNAs, with effects that were sustained during disease, in mutation carriers, and diverse ancestry.

Alum-anchored IL-12 combined with cytotoxic chemotherapy and immune checkpoint blockade enhanced antitumor immune responses in head and neck cancer models.

Background: First-line treatment with pembrolizumab plus chemotherapy in recurrent and metastatic head and neck squamous cell carcinomas (HNSCC) has improved survival. However, the overall response rate with this standard of care regimen (SOC) remains limited. Interleukin (IL)-12 is a potent cytokine that facilitates the crosstalk between innate and adaptive immunity, making it crucial in the antitumor response.

PIK-III exerts anti-fibrotic effects in activated fibroblasts by regulating p38 activation.

Systemic sclerosis (SSc), also known as scleroderma, is an autoimmune-driven connective tissue disorder that results in fibrosis of the skin and internal organs such as the lung. Fibroblasts are known as the main effector cells involved in the progression of SSc through the induction of extracellular matrix (ECM) proteins and myofibroblast differentiation. Here, we demonstrate that 4'-(cyclopropylmethyl)-N2-4-pyridinyl-[4,5'-bipyrimidine]-2,2'-diamine (PIK-III), known as class III phosphatidylinositol 3-kinase (PIK3C3/VPS34) inhibitor, exerts potent antifibrotic effects in human dermal fibroblasts (HDFs) by attenuating transforming growth factor-beta 1 (TGF-β1)-induced ECM expression, cell contraction and myofibroblast differentiation.

Total Knee Arthroplasty in a Patient With Neurofibromatosis 1.

Neurofibromatosis 1 (NF1) is a rare genetic syndrome that leads to the development of neurofibromas and increases the risk of malignancy, including malignant peripheral nerve sheath tumors. Patients with NF1 often have other orthopaedic manifestations, including short stature, osteopenia, and dysplasia. A 47-year-old patient with a history of NF1 and multiple neurofibromas of the right lower extremity presented with a severe valgus deformity, instability, and osteoarthritis of the right knee that was debilitating to daily life.

Diversity and specificity of molecular functions in cyanobacterial symbionts.

Cyanobacteria are globally occurring photosynthetic bacteria notable for their contribution to primary production and production of toxins which have detrimental ecosystem impacts. Furthermore, cyanobacteria can form mutualistic symbiotic relationships with a diverse set of eukaryotes, including land plants, aquatic plankton and fungi. Nevertheless, not all cyanobacteria are found in symbiotic associations suggesting symbiotic cyanobacteria have evolved specializations that facilitate host-interactions.

Digital telomere measurement by long-read sequencing distinguishes healthy aging from disease.

Telomere length is an important biomarker of organismal aging and cellular replicative potential, but existing measurement methods are limited in resolution and accuracy. Here, we deploy digital telomere measurement (DTM) by nanopore sequencing to understand how distributions of human telomere length change with age and disease. We measure telomere attrition and de novo elongation with up to 30 bp resolution in genetically defined populations of human cells, in blood cells from healthy donors and in blood cells from patients with genetic defects in telomere maintenance.

Transverse colon volvulus in a young patient with wandering liver.

We present the case of a 26-year-old male patient with no history of interest who consulted the emergency department due to occlusive symptoms. Urgent CT showed the presence of a transverse colonic volvulus in the context of a heterotopic liver, located in the left hypochondrium. There were no clinical or radiological signs of perforation or ischemia, so urgent endoscopic decompression was performed with subsequent elective surgery with a favorable resolution of the condition.

Circulating blood circular RNA in Parkinson's Disease; a systematic study.

We aimed to identify circRNAs associated with Parkinson's disease (PD) by leveraging 1,848 participants and 1,789 circRNA from two of the largest publicly available studies with longitudinal clinical and blood transcriptomic data. To comprehensively understand changes in circRNAs we performed a cross-sectional study utilizing the last visit of each participant, and a longitudinal (mix model) analysis that included 1,166 participants with at least two time points. We identified 192 circRNAs differentially expressed in PD participants compared to healthy controls, with effects that were consistent in the mixed models, mutation carriers, and diverse ancestry.

A landscape of checkpoint blockade resistance in cancer: underlying mechanisms and current strategies to overcome resistance.

The discovery of immune checkpoints and the development of immune checkpoint inhibitors (ICI) have achieved a durable response in advanced-stage cancer patients. However, there is still a high proportion of patients who do not benefit from ICI therapy due to a lack of response when first treated (primary resistance) or detection of disease progression months after objective response is observed (acquired resistance). Here, we review the current FDA-approved ICI for the treatment of certain solid malignancies, evaluate the contrasting responses to checkpoint blockade in different cancer types, explore the known mechanisms associated with checkpoint blockade resistance (CBR), and assess current strategies in the field that seek to overcome these mechanisms.

Digital telomere measurement by long-read sequencing distinguishes healthy aging from disease.

Telomere length is an important biomarker of organismal aging and cellular replicative potential, but existing measurement methods are limited in resolution and accuracy. Here, we deploy digital telomere measurement by nanopore sequencing to understand how distributions of human telomere length change with age and disease. We measure telomere attrition and elongation with unprecedented resolution in genetically defined populations of human cells, in blood cells from healthy donors and in blood cells from patients with genetic defects in telomere maintenance.

Exploiting docetaxel-induced tumor cell necrosis with tumor targeted delivery of IL-12.

There is strong evidence that chemotherapy can induce tumor necrosis which can be exploited for the targeted delivery of immuno-oncology agents into the tumor microenvironment (TME). We hypothesized that docetaxel, a chemotherapeutic agent that induces necrosis, in combination with the bifunctional molecule NHS-IL-12 (M9241), which delivers recombinant IL-12 through specific targeting of necrotic regions in the tumor, would provide a significant antitumor benefit in the poorly inflamed murine tumor model, EMT6 (breast), and in the moderately immune-infiltrated tumor model, MC38 (colorectal). Docetaxel, as monotherapy or in combination with NHS-IL-12, promoted tumor necrosis, leading to the improved accumulation and retention of NHS-IL-12 in the TME.

MGnify: the microbiome sequence data analysis resource in 2023.

The MGnify platform (https://www.ebi.ac.

Immune targeting of three independent suppressive pathways (TIGIT, PD-L1, TGFβ) provides significant antitumor efficacy in immune checkpoint resistant models.

Immune checkpoint blockade (ICB) therapy, while groundbreaking, must be improved to promote enhanced durable responses and to prevent the development of treatment-refractory disease. Cancer therapies that engage, enable, and expand the antitumor immune response will likely require rationally designed combination strategies. Targeting multiple immunosuppressive pathways simultaneously may provide additional therapeutic benefit over singular targeting.

Tipping the scales: Immunotherapeutic strategies that disrupt immunosuppression and promote immune activation.

Immunotherapy has emerged as an effective therapeutic approach for several cancer types. However, only a subset of patients exhibits a durable response due in part to immunosuppressive mechanisms that allow tumor cells to evade destruction by immune cells. One of the hallmarks of immune suppression is the paucity of tumor-infiltrating lymphocytes (TILs), characterized by low numbers of effector CD4+ and CD8+ T cells in the tumor microenvironment (TME).

A machine learning framework for discovery and enrichment of metagenomics metadata from open access publications.

Metagenomics is a culture-independent method for studying the microbes inhabiting a particular environment. Comparing the composition of samples (functionally/taxonomically), either from a longitudinal study or cross-sectional studies, can provide clues into how the microbiota has adapted to the environment. However, a recurring challenge, especially when comparing results between independent studies, is that key metadata about the sample and molecular methods used to extract and sequence the genetic material are often missing from sequence records, making it difficult to account for confounding factors.

Comparison of Evolocumab and Ezetimibe, Both Combined with Statin Therapy, for Patients with Recent Acute Coronary Syndrome: A Cost-Effectiveness Analysis from the Chinese Healthcare Perspective.

Purpose: To assess the cost-effectiveness of evolocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, compared with ezetimibe, both added to background statin therapy in patients with recent acute coronary syndrome (ACS) events (in the past 12 months) and low-density lipoprotein cholesterol (LDL-C) levels ≥ 100 mg/dL in China.

Methods: A health economic evaluation was performed from a Chinese healthcare perspective, using a Markov model over a lifetime horizon based on a baseline cardiovascular (CV) event rate from claims database data and efficacy from the FOURIER trial. The health benefit was reflected in the decrease of LDL-C level, which led to a decrease of cardiovascular events.

Work-Family Interaction, Self-Perceived Mental Health and Burnout in Specialized Physicians of Huelva (Spain): A Study Conducted during the SARS-CoV-2 Pandemic.

Background: The medical staff who work in specialized healthcare are among the professionals with a greater risk of presenting negative indicators of mental health. These professionals are exposed to numerous sources of stress that can have a negative influence on their personal life. Currently, SARS-CoV-2 poses an additional and relevant source of stress.

Examining the Relationship Between Mild Traumatic Brain Injuries and Development of Mental Illness Disorders in a Mid-Term Follow-up Period.

Objective: The sequalae of mild concussions continue to emerge with increased awareness in sports-related injuries. This study aimed to quantify the number of patients who are affected by a mental illness within 3 yrs of a concussion and identify whether demographic differences exist that may influence a mental illness diagnosis.

Design: Using a nationwide database, data were queried for a diagnosis of concussion, capturing patients aged 18-45 yrs with no previous mental illness, and then identified if these patients were diagnosed with a mental illness within 3 yrs of their concussion.

Nursing Education during the SARS-CoV-2 Pandemic: Assessment of Students' Satisfaction with e-Learning Environment.

The disease caused by the SARS-CoV-2 coronavirus led to the disruption of normality with respect to education, public healthcare and new technologies. Education is a fundamental pillar to increase the knowledge and morale of people. However, due to the lockdown implemented to protect the population from an infection of unknown aetiology, the education system decided to switch from face-to-face education to virtual education.