Hasty Briefsbeta

Bilingual

Loss-of-function variants in ODAD1 disrupt ODA docking and induce actin cytoskeletal remodeling in primary ciliary dyskinesia - PubMed
9 days ago
- ODAD1 loss-of-function variants impair outer dynein arm docking, leading to defective ciliary beating.
- Patients with homozygous ODAD1 variants show hallmark PCD symptoms, low nasal nitric oxide, and situs inversus.
- ODAD1 deficiency reduces multiciliated cell abundance, disrupts basal body orientation, and impairs multiciliogenesis.
- Proteomics and imaging reveal actin cytoskeletal remodeling, with aberrant F-actin bundling in epithelial layers.
- Pharmacological inhibition of actin polymerization partially rescues multiciliated cell defects.
- Wild-type ODAD1 re-expression in organoids restores outer dynein arm assembly and ciliary beating.
The ribosome-associated N-terminal acetyltransferase B coordinates global proteostasis and autophagy in plants by creating Ac/N-degrons - PubMed
9 days ago
- NatB, an N-terminal acetyltransferase, acetylates approximately 20% of eukaryotic proteomes.
- CRISPR-Cas9 deletion of NatB in plants reduces global protein turnover by lowering UPS activity and protein translation.
- NatB substrates are enriched among stabilized proteins in natb mutants, indicating protection from degradation.
- Absent NTA of KIN11 (SnRK1 subunit) shields it from UPS destruction, leading to its accumulation.
- Accumulated KIN11 enhances natb mutant resistance to energy limitation, such as prolonged darkness.
- NatB acts as a key regulator of UPS-autophagy interplay, maintaining proteome stability and stress response in plants.
Autophagy dysfunction in iPSCs-derived neurons and midbrain organoids carrying a SNCA triplication - PubMed
9 days ago
- Autophagy defects observed early in iPSC-derived neuronal cultures from PD patients with SNCA triplication.
- In midbrain organoids (hMOs) with SNCA triplication, autolysosome area decreased, while α-Synuclein levels increased by 50 days of differentiation.
- Autophagy impairment worsened by 70 days, correlating with dopaminergic neuron dysfunction and electrophysiological activity decline.
- Study supports using iPSC-derived models to link autophagy dysfunction, α-Synuclein pathology, and neurodegeneration in Parkinson's disease.
- Live-cell imaging with LC3-Rosella reporter enabled real-time assessment of autolysosome dynamics in human-relevant systems.
Inhibition of tPA-NMDAR interaction prevents neurovascular and functional deficits induced by organophosphorus nerve agents - PubMed
9 days ago
- Organophosphorus compounds (OP) like nerve agents inhibit cholinesterases, leading to excessive cholinergic signaling, excitotoxicity, and neuroinflammation.
- OP exposure increases circulating tissue-type plasminogen activator (tPA), which worsens neuroinflammation, blood-brain barrier leakage, and neurovascular coupling impairment.
- Blocking the interaction between tPA and the N-methyl-D-aspartate receptor (NMDAR) with Glunomab prevents OP-induced neurovascular and functional deficits.
- The study identifies tPA-NMDAR signaling as a key mediator of OP-induced central nervous system damage and a potential therapeutic target.
Phase 1 study of ceralasertib, an ATR kinase inhibitor, in combination with durvalumab in patients with recurrent or metastatic NSCLC or HNSCC - PubMed
9 days ago
- This Phase 1 study evaluated the ATR inhibitor ceralasertib combined with PD-L1 inhibitor durvalumab in advanced/metastatic NSCLC or HNSCC patients.
- Safety and tolerability were the primary objectives, with doses of ceralasertib ranging from 80 mg BID to 320 mg QD.
- Two dose-limiting toxicities occurred: Grade 3 thrombocytopenia with anemia (320 mg QD) and Grade 4 thrombocytopenia with neutropenia (240 mg BID).
- 98.3% of patients experienced treatment-emergent adverse events, and 51.7% had grade ≥3 events.
- The recommended Phase 2 dose is durvalumab 1500 mg on Day 1 plus ceralasertib 240 mg BID from Days 15-28.
- Objective responses were seen in 8.3% of patients, and 51.7% had stable disease.
- Pharmacodynamic activity (pRAD50 increase) was observed in 10 out of 14 paired biopsies.
- The combination was tolerated and showed antitumor activity in these advanced cancers.
Pharmacokinetics of CAR T cells in multiple myeloma - the good, the bad, and the ugly - PubMed
9 days ago
- CAR T cell pharmacokinetics in multiple myeloma has positive, negative, and complex aspects.
- Competing interests and funding disclosures involve multiple pharmaceutical companies and research grants.
- Reference to a 2018 study shows CAR T cells targeting B-cell maturation antigen induce remissions in relapsed multiple myeloma.
From mechanisms to clinical practice: a review of diuretic therapy in pediatric nephrology - PubMed
9 days ago
- Diuretics are essential supportive therapy in pediatric nephrology for managing edema, fluid overload, hypertension, and kidney diseases.
- Clinical use is affected by developmental kidney physiology, age-related pharmacokinetics, underlying diseases, and unique pediatric adverse effects.
- Review covers pharmacology, mechanisms, indications, drug interactions, safety, and roles in conditions like nephrotic syndrome, CKD, AKI, hypertension, hypercalcemia, hypercalciuria, and nephrogenic diabetes insipidus.
- Special populations include neonates and adolescents, with focus on developmental pharmacology, toxicity risks, and long-term growth and bone health concerns.
- Emerging therapies discussed: sodium-glucose cotransporter-2 inhibitors, vasopressin receptor antagonists, and non-steroidal mineralocorticoid receptor antagonists, noting limited pediatric evidence.
- Adverse effects addressed: electrolyte disturbances, nephrocalcinosis, ototoxicity, metabolic complications, with monitoring recommendations.
- Emphasis on judicious, individualized use based on age and kidney function, close monitoring, and integration with definitive therapies.
Effectiveness, immunogenicity and safety of monovalent DS-5670a and bivalent DS-5670a/b SARS-CoV-2 vaccines: results from two randomized, active-comparator, non-inferiority trials - PubMed
9 days ago
- Monovalent DS-5670a and bivalent DS-5670a/b SARS-CoV-2 vaccines were tested as boosters in two randomized trials.
- DS-5670 vaccines use lipid nanoparticle-mRNA platform with RBD-derived antigens from original and Omicron strains.
- Both vaccine compositions met non-inferiority criteria compared to existing vaccines (BNT162b2, mRNA-1273).
- DS-5670 showed effective immune responses and broad neutralization across Omicron sub-lineages.
- No serious adverse events were associated with DS-5670 in either study.
- The platform is suitable for seasonal boosters and adaptable to future SARS-CoV-2 variants.
Mitochondrial DNA as a driver of inflammation via the cGAS-STING pathway - PubMed
9 days ago
- Mitochondrial DNA (mtDNA) acts as a damage-associated molecular pattern (DAMP) that translocates to the cytoplasm and activates the cGAS-STING pathway.
- Activation of the cGAS-STING pathway leads to the production of type I interferons and senescence-associated secretory phenotype (SASP), linking mtDNA to inflammation and cellular senescence.
- The mtDNA-cGAS-STING axis is implicated in various inflammation-related pathologies, including ocular, neurodegenerative, pulmonary, cardiovascular, and oral diseases.
- Targeting the mtDNA-cGAS-STING axis shows promise in preclinical models but faces challenges in specificity, delivery, and side effects for clinical translation.
- Further mechanistic understanding of this axis could provide innovative therapeutic strategies for managing inflammation and aging-associated diseases.
Patient Characteristics and Clinical Outcomes in a Specialist Hypertension Clinic: A Pragmatic Real-World Single-Center Observational Study - PubMed
9 days ago
- A retrospective study of 199 patients at a specialist hypertension clinic found significant blood pressure reductions with an average decrease of -13.6/-8.8 mmHg over a median follow-up of 13.8 months.
- Patients were complex, with 32.7% having secondary hypertension and 17.2% resistant hypertension; BP improvements were consistent across clinical subgroups, including those with diabetes, CKD, and obesity.
- Medication non-adherence identified via qualitative urine screening in some patients, and targeted interventions led to subsequent BP improvements, highlighting the clinical value of objective adherence assessment.
- Cardiovascular events were infrequent at 6.5%, but residual cardiovascular risk persisted, indicating that BP control remains challenging despite specialist care.
- The study advocates for larger multicenter studies with longer follow-up to better define predictors of cardiovascular outcomes and optimize care pathways in hypertension management.
Histologic Regression of Barrett's Esophagus After Antireflux Surgery: Incidence and Predictive Factors - PubMed
9 days ago
- Overall histologic regression of Barrett's esophagus (BE) after antireflux surgery (ARS) occurred in 53.4% of patients.
- Regression rates were highest for ultrashort BE (68.9%), followed by short BE (51.2%), with no regression in long-segment BE.
- An intact antireflux repair (64.2% regression) significantly increased the likelihood of regression compared to a disrupted repair (38.8%).
- Independent predictors of BE regression included an intact repair, absence of severe esophagitis, and shorter BE segment length.
- Patients without regression typically had a more severe reflux phenotype (larger hiatal hernia, severe esophagitis, higher DeMeester score, lower LES pressure).
Current Trends in the Epidemiology of Obesity and the Association Between Obesity and Metabolic Liver Disease (MASLD/MASH) - PubMed
9 days ago
- Obesity and excess adiposity are increasingly prevalent globally, triggering a state of metabo-inflammation that leads to systemic insulin resistance and pro-inflammatory and fibrogenic states.
- Metabolically driven cell stress, injury, and death due to metabolic disruptions activate innate immune signals, promoting fibrogenesis and organ dysfunction in end-organ diseases.
- Key non-communicable diseases associated with obesity and metabo-inflammation include atherosclerotic vascular disease, hypertension, type 2 diabetes mellitus, chronic kidney disease, heart failure with preserved ejection fraction, and metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH).
- MASLD/MASH is part of a cluster of non-communicable diseases that account for the majority of premature deaths worldwide, with rates projected to rise due to obesity, diabetes, and metabolic syndromes.
- The manuscript reviews the epidemiology, biological relationships between obesity and MASLD, mechanistic links between MASLD and other non-communicable diseases, and clinical impacts on patients.
- A holistic approach to caring for individuals with MASLD is recommended, focusing on treating obesity as a root cause while monitoring liver status for potential liver-targeted therapeutics.
- Best practices for obesity-oriented treatment of MASLD are discussed, including the rationale for addressing obesity to manage liver disease.
Human Umbilical Cord Blood Mesenchymal Stem Cells Ameliorate Autism-Like Behaviors in a Valproic Acid-Induced Mouse Model via the IGF-1/Akt Signaling Pathway - PubMed
9 days ago
- Human umbilical cord blood mesenchymal stem cells (hUC-MSCs) improve autism-like behaviors in a valproic acid-induced mouse model of autism spectrum disorder (ASD).
- The therapeutic effects occur without notable adverse effects, as shown by safety assessments including growth monitoring and organ histology.
- Mechanistically, hUC-MSCs promote neuronal dendritic development and restore phosphorylation levels in the IGF-1/Akt signaling pathway.
- Treatment upregulates synaptic plasticity genes (GAP-43, SYP) and anti-inflammatory cytokine IL-10, while suppressing proapoptotic genes (Bax, Caspase-3) and pro-inflammatory cytokines (IL-6, IL-1β).
- Findings suggest hUC-MSCs exert neuroprotective effects via IGF-1/Akt modulation, offering a potential stem cell-based therapy for ASD.
Tadehagi triquetrum aqueous extract ameliorates diabetic kidney disease through mitigating epithelial senescence via the PTEN/AKT/mTOR signaling pathway - PubMed
9 days ago
- TAE improves kidney function and reduces damage in diabetic mice.
- TAE reduces signs of cell aging in kidney disease models.
- TAE works by inhibiting the PTEN/AKT/mTOR pathway.
- Key compounds in TAE include Hesperidin, Quercitrin, and Carnosol.
- TAE shows potential as a treatment for diabetic kidney disease.
Spatial multi-omics characterization of neuroblastoma reveals ferroptosis-associated metabolic features in high-risk tumors - PubMed
9 days ago
- Spatial multi-omics (transcriptomics and proteomics) analysis of neuroblastoma identifies metabolic features linked to ferroptosis in high-risk tumors, including upregulation of fatty acid metabolism and ROS signaling.
- High-risk tumors show increased glutathione metabolism and GPX4 expression, suggesting a compensatory mechanism that may inhibit ferroptosis; GPX4 inhibition in vitro induces lipid peroxidation and reduces cell viability.
- Spatial proteomics reveals distinct niches like stroma-secluded immune cells and macrophage-rich areas in high-risk neuroblastoma, which correlate with poor patient survival and may influence ferroptosis sensitivity.
- The study proposes ferroptosis-associated pathways and macrophage-tumor interactions as potential therapeutic targets for treating high-risk neuroblastoma.
Cross-algorithm machine learning and consensus features for early disseminated intravascular coagulation risk prediction in sepsis-induced coagulopathy - PubMed
9 days ago
- The study proposes a method for early disseminated intravascular coagulation risk prediction in sepsis-induced coagulopathy.
- It utilizes cross-algorithm machine learning and consensus features for the prediction model.
- The research employs a two-stage feature selection approach for interpretability.
- The authors declare no competing interests, stating the research was conducted without commercial or financial conflicts.
- The study is supported by several grants, including from the National Key Research and Development Program of China and the National Natural Science Foundation of China.
Comparison and Evaluation of Efficacy and Safety of Sitagliptin and Linagliptin in Adults With Type 2 Diabetes Mellitus: A Bayesian Network Meta-Analysis - PubMed
9 days ago
- A Bayesian network meta-analysis of 87 RCTs with 64,517 participants compares sitagliptin 100 mg/day and linagliptin 5 mg/day for adults with type 2 diabetes mellitus.
- Both drugs significantly reduce HbA1c and fasting plasma glucose compared to placebo, with no significant differences in efficacy between them.
- Safety profiles show no significant increase in adverse events for either drug versus placebo, and no significant differences in most safety outcomes between them.
- The analysis included a primary analysis of 61 RCTs (28,715 participants) at 24-54 weeks, using Bayesian random-effects models and assessing bias and evidence certainty.
- Conclusions indicate equivalent efficacy and safety for both drugs, with neither significantly superior to other included antidiabetic drugs for glycemic control.
A Real-World Efficacy and Safety of KEYNOTE-522 Regimen in Patients With Early Triple-Negative Breast Cancer - PubMed
9 days ago
- The real-world study evaluated the KEYNOTE-522 regimen (neoadjuvant pembrolizumab plus chemotherapy) in 174 Korean patients with early-stage triple-negative breast cancer (TNBC).
- The overall pathologic complete response (pCR) rate was 62.1%, with high baseline Ki-67 expression (≥75%) significantly associated with achieving pCR (odds ratio, 2.84; p=0.002).
- The 12-month event-free survival (EFS) rate was 97.4%, significantly higher in patients who achieved pCR compared to those who did not (100% vs. 93.1%, p=0.007).
- The treatment completion rate was 92.0%, and immune-related adverse events occurred in 13.8% of patients, indicating manageable toxicity.
Post-marketing safety signals of four JAK inhibitors for alopecia areata: an indication-restricted FAERS pharmacovigilance study - PubMed
9 days ago
- JAK inhibitors for alopecia areata show varied post-marketing safety signals across agents.
- Tofacitinib associated with neuropsychiatric and autoimmune events; baricitinib with thrombocytosis, DVT, and breast cancer.
- Ruxolitinib linked to pyrexia and elevated cholesterol; ritlecitinib with gastrointestinal issues and CPK elevation.
- Time-to-onset differs: earlier for tofacitinib/ruxolitinib, clustered first month for ritlecitinib, delayed for baricitinib.
- Serious outcomes often infection-related, but clinical outcomes vary by agent, suggesting need for agent-specific monitoring.
The Moving Target: Cis-Mutation-Driven Resistance to p53-Y220C Reactivator - PubMed
9 days ago
- Study reveals secondary TP53 mutations drive resistance to p53-Y220C reactivator rezatapopt.
- Resistance observed in PYNNACLE clinical trial, where rezatapopt treatment selects for mutations on Y220C-mutant background.
- Secondary mutations abrogate therapeutic efficacy of rezatapopt.

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Loss-of-function variants in ODAD1 disrupt ODA docking and induce actin cytoskeletal remodeling in primary ciliary dyskinesia - PubMed
9 days ago
- ODAD1 loss-of-function variants impair outer dynein arm docking, leading to defective ciliary beating.
- Patients with homozygous ODAD1 variants show hallmark PCD symptoms, low nasal nitric oxide, and situs inversus.
- ODAD1 deficiency reduces multiciliated cell abundance, disrupts basal body orientation, and impairs multiciliogenesis.
- Proteomics and imaging reveal actin cytoskeletal remodeling, with aberrant F-actin bundling in epithelial layers.
- Pharmacological inhibition of actin polymerization partially rescues multiciliated cell defects.
- Wild-type ODAD1 re-expression in organoids restores outer dynein arm assembly and ciliary beating.
The ribosome-associated N-terminal acetyltransferase B coordinates global proteostasis and autophagy in plants by creating Ac/N-degrons - PubMed
9 days ago
- NatB, an N-terminal acetyltransferase, acetylates approximately 20% of eukaryotic proteomes.
- CRISPR-Cas9 deletion of NatB in plants reduces global protein turnover by lowering UPS activity and protein translation.
- NatB substrates are enriched among stabilized proteins in natb mutants, indicating protection from degradation.
- Absent NTA of KIN11 (SnRK1 subunit) shields it from UPS destruction, leading to its accumulation.
- Accumulated KIN11 enhances natb mutant resistance to energy limitation, such as prolonged darkness.
- NatB acts as a key regulator of UPS-autophagy interplay, maintaining proteome stability and stress response in plants.
Autophagy dysfunction in iPSCs-derived neurons and midbrain organoids carrying a SNCA triplication - PubMed
9 days ago
- Autophagy defects observed early in iPSC-derived neuronal cultures from PD patients with SNCA triplication.
- In midbrain organoids (hMOs) with SNCA triplication, autolysosome area decreased, while α-Synuclein levels increased by 50 days of differentiation.
- Autophagy impairment worsened by 70 days, correlating with dopaminergic neuron dysfunction and electrophysiological activity decline.
- Study supports using iPSC-derived models to link autophagy dysfunction, α-Synuclein pathology, and neurodegeneration in Parkinson's disease.
- Live-cell imaging with LC3-Rosella reporter enabled real-time assessment of autolysosome dynamics in human-relevant systems.
Inhibition of tPA-NMDAR interaction prevents neurovascular and functional deficits induced by organophosphorus nerve agents - PubMed
9 days ago
- Organophosphorus compounds (OP) like nerve agents inhibit cholinesterases, leading to excessive cholinergic signaling, excitotoxicity, and neuroinflammation.
- OP exposure increases circulating tissue-type plasminogen activator (tPA), which worsens neuroinflammation, blood-brain barrier leakage, and neurovascular coupling impairment.
- Blocking the interaction between tPA and the N-methyl-D-aspartate receptor (NMDAR) with Glunomab prevents OP-induced neurovascular and functional deficits.
- The study identifies tPA-NMDAR signaling as a key mediator of OP-induced central nervous system damage and a potential therapeutic target.
Phase 1 study of ceralasertib, an ATR kinase inhibitor, in combination with durvalumab in patients with recurrent or metastatic NSCLC or HNSCC - PubMed
9 days ago
- This Phase 1 study evaluated the ATR inhibitor ceralasertib combined with PD-L1 inhibitor durvalumab in advanced/metastatic NSCLC or HNSCC patients.
- Safety and tolerability were the primary objectives, with doses of ceralasertib ranging from 80 mg BID to 320 mg QD.
- Two dose-limiting toxicities occurred: Grade 3 thrombocytopenia with anemia (320 mg QD) and Grade 4 thrombocytopenia with neutropenia (240 mg BID).
- 98.3% of patients experienced treatment-emergent adverse events, and 51.7% had grade ≥3 events.
- The recommended Phase 2 dose is durvalumab 1500 mg on Day 1 plus ceralasertib 240 mg BID from Days 15-28.
- Objective responses were seen in 8.3% of patients, and 51.7% had stable disease.
- Pharmacodynamic activity (pRAD50 increase) was observed in 10 out of 14 paired biopsies.
- The combination was tolerated and showed antitumor activity in these advanced cancers.
Pharmacokinetics of CAR T cells in multiple myeloma - the good, the bad, and the ugly - PubMed
9 days ago
- CAR T cell pharmacokinetics in multiple myeloma has positive, negative, and complex aspects.
- Competing interests and funding disclosures involve multiple pharmaceutical companies and research grants.
- Reference to a 2018 study shows CAR T cells targeting B-cell maturation antigen induce remissions in relapsed multiple myeloma.
From mechanisms to clinical practice: a review of diuretic therapy in pediatric nephrology - PubMed
9 days ago
- Diuretics are essential supportive therapy in pediatric nephrology for managing edema, fluid overload, hypertension, and kidney diseases.
- Clinical use is affected by developmental kidney physiology, age-related pharmacokinetics, underlying diseases, and unique pediatric adverse effects.
- Review covers pharmacology, mechanisms, indications, drug interactions, safety, and roles in conditions like nephrotic syndrome, CKD, AKI, hypertension, hypercalcemia, hypercalciuria, and nephrogenic diabetes insipidus.
- Special populations include neonates and adolescents, with focus on developmental pharmacology, toxicity risks, and long-term growth and bone health concerns.
- Emerging therapies discussed: sodium-glucose cotransporter-2 inhibitors, vasopressin receptor antagonists, and non-steroidal mineralocorticoid receptor antagonists, noting limited pediatric evidence.
- Adverse effects addressed: electrolyte disturbances, nephrocalcinosis, ototoxicity, metabolic complications, with monitoring recommendations.
- Emphasis on judicious, individualized use based on age and kidney function, close monitoring, and integration with definitive therapies.
Effectiveness, immunogenicity and safety of monovalent DS-5670a and bivalent DS-5670a/b SARS-CoV-2 vaccines: results from two randomized, active-comparator, non-inferiority trials - PubMed
9 days ago
- Monovalent DS-5670a and bivalent DS-5670a/b SARS-CoV-2 vaccines were tested as boosters in two randomized trials.
- DS-5670 vaccines use lipid nanoparticle-mRNA platform with RBD-derived antigens from original and Omicron strains.
- Both vaccine compositions met non-inferiority criteria compared to existing vaccines (BNT162b2, mRNA-1273).
- DS-5670 showed effective immune responses and broad neutralization across Omicron sub-lineages.
- No serious adverse events were associated with DS-5670 in either study.
- The platform is suitable for seasonal boosters and adaptable to future SARS-CoV-2 variants.
Mitochondrial DNA as a driver of inflammation via the cGAS-STING pathway - PubMed
9 days ago
- Mitochondrial DNA (mtDNA) acts as a damage-associated molecular pattern (DAMP) that translocates to the cytoplasm and activates the cGAS-STING pathway.
- Activation of the cGAS-STING pathway leads to the production of type I interferons and senescence-associated secretory phenotype (SASP), linking mtDNA to inflammation and cellular senescence.
- The mtDNA-cGAS-STING axis is implicated in various inflammation-related pathologies, including ocular, neurodegenerative, pulmonary, cardiovascular, and oral diseases.
- Targeting the mtDNA-cGAS-STING axis shows promise in preclinical models but faces challenges in specificity, delivery, and side effects for clinical translation.
- Further mechanistic understanding of this axis could provide innovative therapeutic strategies for managing inflammation and aging-associated diseases.
Patient Characteristics and Clinical Outcomes in a Specialist Hypertension Clinic: A Pragmatic Real-World Single-Center Observational Study - PubMed
9 days ago
- A retrospective study of 199 patients at a specialist hypertension clinic found significant blood pressure reductions with an average decrease of -13.6/-8.8 mmHg over a median follow-up of 13.8 months.
- Patients were complex, with 32.7% having secondary hypertension and 17.2% resistant hypertension; BP improvements were consistent across clinical subgroups, including those with diabetes, CKD, and obesity.
- Medication non-adherence identified via qualitative urine screening in some patients, and targeted interventions led to subsequent BP improvements, highlighting the clinical value of objective adherence assessment.
- Cardiovascular events were infrequent at 6.5%, but residual cardiovascular risk persisted, indicating that BP control remains challenging despite specialist care.
- The study advocates for larger multicenter studies with longer follow-up to better define predictors of cardiovascular outcomes and optimize care pathways in hypertension management.
Histologic Regression of Barrett's Esophagus After Antireflux Surgery: Incidence and Predictive Factors - PubMed
9 days ago
- Overall histologic regression of Barrett's esophagus (BE) after antireflux surgery (ARS) occurred in 53.4% of patients.
- Regression rates were highest for ultrashort BE (68.9%), followed by short BE (51.2%), with no regression in long-segment BE.
- An intact antireflux repair (64.2% regression) significantly increased the likelihood of regression compared to a disrupted repair (38.8%).
- Independent predictors of BE regression included an intact repair, absence of severe esophagitis, and shorter BE segment length.
- Patients without regression typically had a more severe reflux phenotype (larger hiatal hernia, severe esophagitis, higher DeMeester score, lower LES pressure).
Current Trends in the Epidemiology of Obesity and the Association Between Obesity and Metabolic Liver Disease (MASLD/MASH) - PubMed
9 days ago
- Obesity and excess adiposity are increasingly prevalent globally, triggering a state of metabo-inflammation that leads to systemic insulin resistance and pro-inflammatory and fibrogenic states.
- Metabolically driven cell stress, injury, and death due to metabolic disruptions activate innate immune signals, promoting fibrogenesis and organ dysfunction in end-organ diseases.
- Key non-communicable diseases associated with obesity and metabo-inflammation include atherosclerotic vascular disease, hypertension, type 2 diabetes mellitus, chronic kidney disease, heart failure with preserved ejection fraction, and metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH).
- MASLD/MASH is part of a cluster of non-communicable diseases that account for the majority of premature deaths worldwide, with rates projected to rise due to obesity, diabetes, and metabolic syndromes.
- The manuscript reviews the epidemiology, biological relationships between obesity and MASLD, mechanistic links between MASLD and other non-communicable diseases, and clinical impacts on patients.
- A holistic approach to caring for individuals with MASLD is recommended, focusing on treating obesity as a root cause while monitoring liver status for potential liver-targeted therapeutics.
- Best practices for obesity-oriented treatment of MASLD are discussed, including the rationale for addressing obesity to manage liver disease.
Human Umbilical Cord Blood Mesenchymal Stem Cells Ameliorate Autism-Like Behaviors in a Valproic Acid-Induced Mouse Model via the IGF-1/Akt Signaling Pathway - PubMed
9 days ago
- Human umbilical cord blood mesenchymal stem cells (hUC-MSCs) improve autism-like behaviors in a valproic acid-induced mouse model of autism spectrum disorder (ASD).
- The therapeutic effects occur without notable adverse effects, as shown by safety assessments including growth monitoring and organ histology.
- Mechanistically, hUC-MSCs promote neuronal dendritic development and restore phosphorylation levels in the IGF-1/Akt signaling pathway.
- Treatment upregulates synaptic plasticity genes (GAP-43, SYP) and anti-inflammatory cytokine IL-10, while suppressing proapoptotic genes (Bax, Caspase-3) and pro-inflammatory cytokines (IL-6, IL-1β).
- Findings suggest hUC-MSCs exert neuroprotective effects via IGF-1/Akt modulation, offering a potential stem cell-based therapy for ASD.
Tadehagi triquetrum aqueous extract ameliorates diabetic kidney disease through mitigating epithelial senescence via the PTEN/AKT/mTOR signaling pathway - PubMed
9 days ago
- TAE improves kidney function and reduces damage in diabetic mice.
- TAE reduces signs of cell aging in kidney disease models.
- TAE works by inhibiting the PTEN/AKT/mTOR pathway.
- Key compounds in TAE include Hesperidin, Quercitrin, and Carnosol.
- TAE shows potential as a treatment for diabetic kidney disease.
Spatial multi-omics characterization of neuroblastoma reveals ferroptosis-associated metabolic features in high-risk tumors - PubMed
9 days ago
- Spatial multi-omics (transcriptomics and proteomics) analysis of neuroblastoma identifies metabolic features linked to ferroptosis in high-risk tumors, including upregulation of fatty acid metabolism and ROS signaling.
- High-risk tumors show increased glutathione metabolism and GPX4 expression, suggesting a compensatory mechanism that may inhibit ferroptosis; GPX4 inhibition in vitro induces lipid peroxidation and reduces cell viability.
- Spatial proteomics reveals distinct niches like stroma-secluded immune cells and macrophage-rich areas in high-risk neuroblastoma, which correlate with poor patient survival and may influence ferroptosis sensitivity.
- The study proposes ferroptosis-associated pathways and macrophage-tumor interactions as potential therapeutic targets for treating high-risk neuroblastoma.
Cross-algorithm machine learning and consensus features for early disseminated intravascular coagulation risk prediction in sepsis-induced coagulopathy - PubMed
9 days ago
- The study proposes a method for early disseminated intravascular coagulation risk prediction in sepsis-induced coagulopathy.
- It utilizes cross-algorithm machine learning and consensus features for the prediction model.
- The research employs a two-stage feature selection approach for interpretability.
- The authors declare no competing interests, stating the research was conducted without commercial or financial conflicts.
- The study is supported by several grants, including from the National Key Research and Development Program of China and the National Natural Science Foundation of China.
Comparison and Evaluation of Efficacy and Safety of Sitagliptin and Linagliptin in Adults With Type 2 Diabetes Mellitus: A Bayesian Network Meta-Analysis - PubMed
9 days ago
- A Bayesian network meta-analysis of 87 RCTs with 64,517 participants compares sitagliptin 100 mg/day and linagliptin 5 mg/day for adults with type 2 diabetes mellitus.
- Both drugs significantly reduce HbA1c and fasting plasma glucose compared to placebo, with no significant differences in efficacy between them.
- Safety profiles show no significant increase in adverse events for either drug versus placebo, and no significant differences in most safety outcomes between them.
- The analysis included a primary analysis of 61 RCTs (28,715 participants) at 24-54 weeks, using Bayesian random-effects models and assessing bias and evidence certainty.
- Conclusions indicate equivalent efficacy and safety for both drugs, with neither significantly superior to other included antidiabetic drugs for glycemic control.
A Real-World Efficacy and Safety of KEYNOTE-522 Regimen in Patients With Early Triple-Negative Breast Cancer - PubMed
9 days ago
- The real-world study evaluated the KEYNOTE-522 regimen (neoadjuvant pembrolizumab plus chemotherapy) in 174 Korean patients with early-stage triple-negative breast cancer (TNBC).
- The overall pathologic complete response (pCR) rate was 62.1%, with high baseline Ki-67 expression (≥75%) significantly associated with achieving pCR (odds ratio, 2.84; p=0.002).
- The 12-month event-free survival (EFS) rate was 97.4%, significantly higher in patients who achieved pCR compared to those who did not (100% vs. 93.1%, p=0.007).
- The treatment completion rate was 92.0%, and immune-related adverse events occurred in 13.8% of patients, indicating manageable toxicity.
Post-marketing safety signals of four JAK inhibitors for alopecia areata: an indication-restricted FAERS pharmacovigilance study - PubMed
9 days ago
- JAK inhibitors for alopecia areata show varied post-marketing safety signals across agents.
- Tofacitinib associated with neuropsychiatric and autoimmune events; baricitinib with thrombocytosis, DVT, and breast cancer.
- Ruxolitinib linked to pyrexia and elevated cholesterol; ritlecitinib with gastrointestinal issues and CPK elevation.
- Time-to-onset differs: earlier for tofacitinib/ruxolitinib, clustered first month for ritlecitinib, delayed for baricitinib.
- Serious outcomes often infection-related, but clinical outcomes vary by agent, suggesting need for agent-specific monitoring.
The Moving Target: Cis-Mutation-Driven Resistance to p53-Y220C Reactivator - PubMed
9 days ago
- Study reveals secondary TP53 mutations drive resistance to p53-Y220C reactivator rezatapopt.
- Resistance observed in PYNNACLE clinical trial, where rezatapopt treatment selects for mutations on Y220C-mutant background.
- Secondary mutations abrogate therapeutic efficacy of rezatapopt.

Hasty Briefsbeta

Loss-of-function variants in ODAD1 disrupt ODA docking and induce actin cytoskeletal remodeling in primary ciliary dyskinesia - PubMed

The ribosome-associated N-terminal acetyltransferase B coordinates global proteostasis and autophagy in plants by creating Ac/N-degrons - PubMed

Autophagy dysfunction in iPSCs-derived neurons and midbrain organoids carrying a SNCA triplication - PubMed

Inhibition of tPA-NMDAR interaction prevents neurovascular and functional deficits induced by organophosphorus nerve agents - PubMed

Phase 1 study of ceralasertib, an ATR kinase inhibitor, in combination with durvalumab in patients with recurrent or metastatic NSCLC or HNSCC - PubMed

Pharmacokinetics of CAR T cells in multiple myeloma - the good, the bad, and the ugly - PubMed

From mechanisms to clinical practice: a review of diuretic therapy in pediatric nephrology - PubMed

Effectiveness, immunogenicity and safety of monovalent DS-5670a and bivalent DS-5670a/b SARS-CoV-2 vaccines: results from two randomized, active-comparator, non-inferiority trials - PubMed

Mitochondrial DNA as a driver of inflammation via the cGAS-STING pathway - PubMed

Patient Characteristics and Clinical Outcomes in a Specialist Hypertension Clinic: A Pragmatic Real-World Single-Center Observational Study - PubMed

Histologic Regression of Barrett's Esophagus After Antireflux Surgery: Incidence and Predictive Factors - PubMed

Current Trends in the Epidemiology of Obesity and the Association Between Obesity and Metabolic Liver Disease (MASLD/MASH) - PubMed

Human Umbilical Cord Blood Mesenchymal Stem Cells Ameliorate Autism-Like Behaviors in a Valproic Acid-Induced Mouse Model via the IGF-1/Akt Signaling Pathway - PubMed

Tadehagi triquetrum aqueous extract ameliorates diabetic kidney disease through mitigating epithelial senescence via the PTEN/AKT/mTOR signaling pathway - PubMed

Spatial multi-omics characterization of neuroblastoma reveals ferroptosis-associated metabolic features in high-risk tumors - PubMed

Cross-algorithm machine learning and consensus features for early disseminated intravascular coagulation risk prediction in sepsis-induced coagulopathy - PubMed

Comparison and Evaluation of Efficacy and Safety of Sitagliptin and Linagliptin in Adults With Type 2 Diabetes Mellitus: A Bayesian Network Meta-Analysis - PubMed

A Real-World Efficacy and Safety of KEYNOTE-522 Regimen in Patients With Early Triple-Negative Breast Cancer - PubMed

Post-marketing safety signals of four JAK inhibitors for alopecia areata: an indication-restricted FAERS pharmacovigilance study - PubMed

The Moving Target: Cis-Mutation-Driven Resistance to p53-Y220C Reactivator - PubMed

Loss-of-function variants in ODAD1 disrupt ODA docking and induce actin cytoskeletal remodeling in primary ciliary dyskinesia - PubMed

The ribosome-associated N-terminal acetyltransferase B coordinates global proteostasis and autophagy in plants by creating Ac/N-degrons - PubMed

Autophagy dysfunction in iPSCs-derived neurons and midbrain organoids carrying a SNCA triplication - PubMed

Inhibition of tPA-NMDAR interaction prevents neurovascular and functional deficits induced by organophosphorus nerve agents - PubMed

Phase 1 study of ceralasertib, an ATR kinase inhibitor, in combination with durvalumab in patients with recurrent or metastatic NSCLC or HNSCC - PubMed

Pharmacokinetics of CAR T cells in multiple myeloma - the good, the bad, and the ugly - PubMed

From mechanisms to clinical practice: a review of diuretic therapy in pediatric nephrology - PubMed

Effectiveness, immunogenicity and safety of monovalent DS-5670a and bivalent DS-5670a/b SARS-CoV-2 vaccines: results from two randomized, active-comparator, non-inferiority trials - PubMed

Mitochondrial DNA as a driver of inflammation via the cGAS-STING pathway - PubMed

Patient Characteristics and Clinical Outcomes in a Specialist Hypertension Clinic: A Pragmatic Real-World Single-Center Observational Study - PubMed

Histologic Regression of Barrett's Esophagus After Antireflux Surgery: Incidence and Predictive Factors - PubMed

Current Trends in the Epidemiology of Obesity and the Association Between Obesity and Metabolic Liver Disease (MASLD/MASH) - PubMed

Human Umbilical Cord Blood Mesenchymal Stem Cells Ameliorate Autism-Like Behaviors in a Valproic Acid-Induced Mouse Model via the IGF-1/Akt Signaling Pathway - PubMed

Tadehagi triquetrum aqueous extract ameliorates diabetic kidney disease through mitigating epithelial senescence via the PTEN/AKT/mTOR signaling pathway - PubMed

Spatial multi-omics characterization of neuroblastoma reveals ferroptosis-associated metabolic features in high-risk tumors - PubMed

Cross-algorithm machine learning and consensus features for early disseminated intravascular coagulation risk prediction in sepsis-induced coagulopathy - PubMed

Comparison and Evaluation of Efficacy and Safety of Sitagliptin and Linagliptin in Adults With Type 2 Diabetes Mellitus: A Bayesian Network Meta-Analysis - PubMed

A Real-World Efficacy and Safety of KEYNOTE-522 Regimen in Patients With Early Triple-Negative Breast Cancer - PubMed

Post-marketing safety signals of four JAK inhibitors for alopecia areata: an indication-restricted FAERS pharmacovigilance study - PubMed

The Moving Target: Cis-Mutation-Driven Resistance to p53-Y220C Reactivator - PubMed