Cellular and metabolic function of GIRK1 potassium channels expressed by arcuate POMC and NPY/AgRP neurons.

It is well known that the G protein-gated inwardly rectifying K (GIRK) channels are critical to maintain excitability of central neurons. GIRK channels consist of 4 subunits and GIRK1/GIRK2 heterotetramers are considered to be the neuronal prototype. We previously reported the metabolic significance of GIRK2 subunits expressed by the neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons of the arcuate nucleus of the hypothalamus (ARH).

Trends, Sociodemographic and Hospital-Level Factors Associated with Palliative Care Utilization Among Metastatic Prostate Cancer Patients.

Several factors are reported to be associated with palliative care utilization among patients with various cancers, but literature is lacking on metastatic prostate cancer (MPC) specific factors. Early integration of palliative care in management of MPC patients could increase their quality of life and overall outcomes. Retrospective longitudinal analyses were conducted using the National Inpatient Sample (NIS) data (2010 - 2019).

Redefining Clinical Hyperprogression: The Incidence, Clinical Implications, and Risk Factors of Hyperprogression in Non-Small Cell Lung Cancer Treated with Immunotherapy.

Introduction: Immune checkpoint inhibitors (ICIs) may be associated with hyperprogressive disease (HPD). However, there is currently no standardized definition of HPD, with its risk factors and clinical implications remaining unclear. We investigated HPD in lung cancer patients undergoing immunotherapy, aiming to redefine HPD, identify risk factors, and assess its impact on survival.

Personalized, tumor-informed, circulating tumor DNA assay for detecting minimal residual disease in non-small cell lung cancer patients receiving curative treatments.

Background: Circulating tumor DNA (ctDNA) has emerged as a prognostic and predictive biomarker for detection of minimal residual disease (MRD), monitoring treatment response, and early detection of recurrence in cancer patients. In this study, we explored the utility of ctDNA-based MRD detection to predict recurrence in a real-world cohort of primarily early-stage non-small cell lung cancer (NSCLC) patients treated with curative intent.

Methods: Longitudinal plasma samples were collected post curative-intent treatment from 36 patients with stage I-IV NSCLC.

Current Status of Anti-Reflux Surgery as a Treatment for GERD.

Anti-reflux surgery (ARS) is an efficient treatment option for gastroesophageal reflux disease (GERD). Despite growing evidence of the efficacy and safety of ARS, medications including proton pump inhibitors (PPIs) remain the most commonly administered treatments for GERD. Meanwhile, ARS can be an effective treatment option for patients who need medications continuously or for those who are refractory to PPI treatment, if proper candidates are selected.

Deep response to a combination of mTOR inhibitor temsirolimus and dual immunotherapy of nivolumab/ipilimumab in poorly differentiated thyroid carcinoma with mutation: a case report and literature review.

Treating advanced thyroid cancer presents challenges due to its resistance to various treatment modalities, thereby limiting therapeutic options. To our knowledge, this study is the first to report the efficacy of temsirolimus in conjunction with dual immunotherapy of nivolumab/ipilimumab to treat heavily treated advanced PDTC. A 50-year-old female initially presented with a rapidly enlarging mass on her right neck.

GIRK2 potassium channels expressed by the AgRP neurons decrease adiposity and body weight in mice.

It is well known that the neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons increase appetite and decrease thermogenesis. Previous studies demonstrated that optogenetic and/or chemogenetic manipulations of NPY/AgRP neuronal activity alter food intake and/or energy expenditure (EE). However, little is known about intrinsic molecules regulating NPY/AgRP neuronal excitability to affect long-term metabolic function.

Differentiation Syndrome in a Patient With NSCLC Harboring Mutation Treated With Enasidenib: Case Report.

gain-of-function mutations cause DNA hypermethylation interfering with cellular differentiation and are linked to poor disease outcomes in NSCLC. inhibitor enasidenib is approved for refractory acute myeloid leukemia but has been associated with delayed onset of differentiation syndrome-a potentially fatal inflammatory reaction caused by differentiating agents, namely all-trans retinoic acid and arsenic trioxide. We report the first case of differentiation syndrome in a patient with NSCLC treated with enasidenib, who after 7 weeks experienced bilateral peripheral edema and shortness of breath, with scans exhibiting pericardial effusion and ground-glass opacities suggestive of pneumonitis.

Melanocortin-4 receptors activate sympathetic preganglionic neurons and elevate blood pressure via TRPV1.

Melanocortin-4 receptors (MC4Rs) expressed by the central nervous system are essential regulators of energy homeostasis, and Mc4r mutation is the most common cause of human monogenic obesity. Notably, patients with obesity carrying Mc4r mutations are protected against obesity-induced hypertension, and MC4R agonists elevate blood pressure (BP). Although increased sympathetic tone by MC4Rs is suggested to underlie this phenotype, the detailed mechanisms remain unclear.

Delineating a serotonin 1B receptor circuit for appetite suppression in mice.

Triptans are a class of commonly prescribed antimigraine drugs. Here, we report a previously unrecognized role for them to suppress appetite in mice. In particular, frovatriptan treatment reduces food intake and body weight in diet-induced obese mice.

Association of HLA class I homozygosity with unfavorable clinical outcomes in patients with non-small cell lung cancer treated with chemo-immunotherapy or immunotherapy as first-line therapy.

Background: Homozygosity at HLA-I locus has been reported to be an unfavorable predictive biomarker of second-line or beyond immunotherapy in patients with different types of cancer. The linkage between HLA-I zygosity and survival in NSCLC patients treated with first-line immunotherapy with or without chemotherapy has not been reported.

Methods: Next generation sequencing with HLA genotyping was performed on patients with advanced NSCLC treated with immune checkpoint inhibitors with or without chemotherapy as first-line (N = 29).

Generation of caudal-type serotonin neurons and hindbrain-fate organoids from hPSCs.

Serotonin (5-HT) neurons, the major components of the raphe nuclei, arise from ventral hindbrain progenitors. Based on anatomical location and axonal projection, 5-HT neurons are coarsely divided into rostral and caudal groups. Here, we propose a novel strategy to generate hindbrain 5-HT neurons from human pluripotent stem cells (hPSCs), which involves the formation of ventral-type neural progenitor cells and stimulation of the hindbrain 5-HT neural development.

Blood transfusions may adversely affect survival outcomes of patients with lung cancer: a systematic review and meta-analysis.

Background: Despite common use in clinical practice, the impact of blood transfusions on prognosis among patients with lung cancer remains unclear. The purpose of the current study is to perform an updated systematic review and meta-analysis to evaluate the influence of blood transfusions on survival outcomes of lung cancer patients.

Methods: We searched PubMed, Embase, Cochrane Library, and Ovid MEDLINE for publications illustrating the association between blood transfusions and prognosis among people with lung cancer from inception to November 2019.

Postoperative nutritional outcomes and quality of life-related complications of proximal versus total gastrectomy for upper-third early gastric cancer: a meta-analysis.

Although proximal gastrectomy (PG) provides superior nutritional outcomes over total gastrectomy (TG) in upper-third early gastric cancer (EGC), surgeons are reluctant to perform PG due to the high rate of postoperative reflux. This meta-analysis aimed to comprehensively compare operative outcomes, nutritional outcomes, and quality of life-related complications between TG and PG performed with esophagogastrostomy (EG), jejunal interposition, or double-tract reconstruction (DTR) to reduce reflux after PG. After searching PubMed, Embase, Medline, and Web of Science databases, 25 studies comparing PG with TG in upper-third EGC published up to October 2020 were identified.

Trends in laparoscopic anti-reflux surgery: a Korea nationwide study.

Background: In 2014, the results derived from the nationwide data of the Korean Anti-reflux Surgery Study (KARS) demonstrated short-term feasibility and safety of anti-reflux surgery. This study aimed to update the longer-term safety and feasibility of laparoscopic anti-reflux surgery up to 1-year follow-up with the KARS nationwide cohort.

Methods: The data of 310 patients with GERD who received anti-reflux surgery up to 2018 were analyzed.

Laparoscopic total gastrectomy as a valid procedure to treat gastric cancer option both in early and advanced stage: A systematic review and meta-analysis.

Although laparoscopic total gastrectomy (LTG) compared to open total gastrectomy (OTG) has been widely used for advanced gastric cancer patients, its oncologic validity is yet to be proven. We performed systemic review and meta-analysis to compare LTG versus OTG for early and advanced stages of gastric cancer. Short- and long-term outcomes of both procedures were analyzed using original studies collected by searching Google Scholar, Medline, PubMed, Embase, and Cochrane library in accordance with the PRISMA guidelines.

Specification and spatial arrangement of cells in the germline stem cell niche of the Drosophila ovary depend on the Maf transcription factor Traffic jam.

Germline stem cells in the Drosophila ovary are maintained by a somatic niche. The niche is structurally and functionally complex and contains four cell types, the escort, cap, and terminal filament cells and the newly identified transition cell. We find that the large Maf transcription factor Traffic jam (Tj) is essential for determining niche cell fates and architecture, enabling each niche in the ovary to support a normal complement of 2-3 germline stem cells.

Myosin II promotes the anisotropic loss of the apical domain during neuroblast ingression.

Epithelial-mesenchymal transitions play key roles in development and cancer and entail the loss of epithelial polarity and cell adhesion. In this study, we use quantitative live imaging of ingressing neuroblasts (NBs) in embryos to assess apical domain loss and junctional disassembly. Ingression is independent of the Snail family of transcriptional repressors and down-regulation of E-cadherin (DEcad) transcription.

Polymer Thin Films with Tunable Acetylcholine-like Functionality Enable Long-Term Culture of Primary Hippocampal Neurons.

In vitro culture systems for primary neurons have served as useful tools for neuroscience research. However, conventional in vitro culture methods are still plagued by challenging problems with respect to applications to neurodegenerative disease models or neuron-based biosensors and neural chips, which commonly require long-term culture of neural cells. These impediments highlight the necessity of developing a platform capable of sustaining neural activity over months.

Islet-like organoids derived from human pluripotent stem cells efficiently function in the glucose responsiveness in vitro and in vivo.

Insulin secretion is elaborately modulated in pancreatic ß cells within islets of three-dimensional (3D) structures. Using human pluripotent stem cells (hPSCs) to develop islet-like structures with insulin-producing ß cells for the treatment of diabetes is challenging. Here, we report that pancreatic islet-like clusters derived from hESCs are functionally capable of glucose-responsive insulin secretion as well as therapeutic effects.

Leptin and insulin engage specific PI3K subunits in hypothalamic SF1 neurons.

Objective: The ventromedial hypothalamic nucleus (VMH) regulates energy balance and glucose homeostasis. Leptin and insulin exert metabolic effects via their cognate receptors expressed by the steroidogenic factor 1 (SF1) neurons within the VMH. However, detailed cellular mechanisms involved in the regulation of these neurons by leptin and insulin remain to be identified.

Gas adsorption properties of highly porous metal-organic frameworks containing functionalized naphthalene dicarboxylate linkers.

Three functionalized metal-organic frameworks (MOFs), MOF-205-NH2, MOF-205-NO2, and MOF-205-OBn, formulated as Zn4O(BTB)4/3(L), where BTB is benzene-1,3,5-tribenzoate and L is 1-aminonaphthalene-3,7-dicarboxylate (NDC-NH2), 1-nitronaphthalene-3,7-dicarboxylate (NDC-NO2) or 1,5-dibenzyloxy-2,6-naphthalenedicarboxylate (NDC-(OBn)2), were synthesized and their gas (H2, CO2, or CH4) adsorption properties were compared to those of the un-functionalized, parent MOF-205. Ordered structural models for MOF-205 and its derivatives were built based on the crystal structures and were subsequently used for predicting porosity properties. Although the Brunauer-Emmett-Teller (BET) surface areas of the three MOF-205 derivatives were reduced (MOF-205, 4460; MOF-205-NH2, 4330; MOF-205-NO2, 3980; MOF-205-OBn, 3470 m(2) g(-1)), all three derivatives were shown to have enhanced H2 adsorption capacities at 77 K and CO2 uptakes at 253, 273, and 298 K respectively at 1 bar in comparison with MOF-205.