1,612,636 results match your criteria small


EGFR binding Fc domain-drug conjugates: stable and highly potent cytotoxic molecules mediate selective cell killing.

Biol Chem 2021 Sep 20. Epub 2021 Sep 20.

ADCs & Targeted NBE Therapeutics, Merck KGaA, Frankfurter Str. 250, D-64293Darmstadt, Germany.

The exposition of cancer cells to cytotoxic doses of payload is fundamental for the therapeutic efficacy of antibody drug conjugates (ADCs) in solid cancers. To maximize payload exposure, tissue penetration can be increased by utilizing smaller-sized drug conjugates which distribute deeper into the tumor. Our group recently explored small human epidermal growth factor receptor 2 (HER2) targeting Fc antigen binding fragments (Fcabs) for ADC applications in a feasibility study. Read More

View Article and Full-Text PDF
September 2021

A liquid-culture-based screening approach to study compounds affecting inflammatory processes in .

Biol Chem 2021 Sep 20. Epub 2021 Sep 20.

Department of Psychiatry and Psychotherapy, University Medical Centre of the Johannes Gutenberg-University Mainz, D-55131Mainz, Germany.

Discovery of biomedical drugs makes use of novel biological sources of limited availability and is often in need of fast, small-scale initial screening approaches. Here, we present a screening, based on the reporter strain IG692, for identification of anti- and pro-inflammatory properties. The elaborated workflow is based on cultivation in fluid and by this, allows fast and reproducible seeding in 96 well plates. Read More

View Article and Full-Text PDF
September 2021

Advanced cardiac life support: lessons from recent trials on how to move forward.

Curr Opin Crit Care 2021 Sep 15. Epub 2021 Sep 15.

Division of Pulmonary, Critical Care and Sleep Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA Anaesthetics Department, Southmead Hospital, North Bristol NHS Trust, Bristol, UK.

Purpose Of Review: This review discusses potential reasons why many recent large trials in advanced cardiac life support have failed to demonstrate a difference in outcomes and suggests some points for consideration in planning future trials.

Recent Findings: The ARREST trial, a small controlled trial studying the effect of intra-arrest extracorporeal membrane oxygenation (ECMO, or E-CPR) on survival and functional outcome in patients with refractory ventricular fibrillation cardiac arrest, was stopped after 30 patients for benefit. This stands in contrast to several recent trials enrolling up to several thousand patients and finding no difference. Read More

View Article and Full-Text PDF
September 2021

Histologic and Molecular Characterization of Non-Small Cell Lung Carcinoma With Discordant ROS1 Immunohistochemistry and Fluorescence In Situ Hybridization.

Appl Immunohistochem Mol Morphol 2021 Sep 16. Epub 2021 Sep 16.

University of Utah and ARUP Laboratories, Salt Lake City, UT St. Jude Childrens' Research Hospital, Memphis, TN.

Introduction: ROS1 immunohistochemical (IHC) positivity requires follow-up with confirmatory testing such as fluorescence in situ hybridization (FISH). Identifying predictive characteristics of false positive ROS1 IHC cases could aid in optimizing testing algorithms, decrease testing costs and preserve tissue.

Materials And Methods: Retrospective results were retrieved for 2054 patients with non-small cell lung carcinoma submitted to our laboratory for molecular testing. Read More

View Article and Full-Text PDF
September 2021

Associations of metabolomic profiles with circulating vitamin E and urinary vitamin E metabolites in middle-aged individuals.

Nutrition 2021 Jul 29;93:111440. Epub 2021 Jul 29.

Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.

Vitamin E (α-tocopherol [α-TOH]) is transported in lipoprotein particles in blood, but little is known about the transportation of its oxidized metabolites. In the Netherlands Epidemiology of Obesity Study, we aimed to investigate the associations of 147 circulating metabolomic measures obtained through targeted nuclear magnetic resonance with serum α-TOH and its urinary enzymatic (α-CEHC) and oxidized (α-TLHQ) metabolites from 24-h urine quantified by liquid chromatography with tandem mass spectrometry. Multivariable linear regression analyses, in which multiple testing was taken into account, were performed to assess associations between metabolomic measures (determinants; standardized to mean = 0, SD = 1) and vitamin E metabolites (outcomes), adjusted for demographic factors. Read More

View Article and Full-Text PDF

Water circulation and impact on water quality in the southwest of Efate Island, Vanuatu.

Mar Pollut Bull 2021 Sep 14;173(Pt A):112938. Epub 2021 Sep 14.

UNICEF, Port Vila, Vanuatu.

In Small Island Developing States (SIDS), water pollution is not monitored or assessed frequently enough to fully understand the processes, impacts of water quality issues and what solutions are available This study investigated flushing time in Erakor lagoon and Port Vila Bay, Vanuatu using a numerical model developed in Delft3D. Microbial contamination by Escherichia coli was detected in multiple locations in the lagoon system with counts exceeding thresholds related to human health concerns. Modelling demonstrated a poor flushing time overall with a further decrease as the influence of waves and wind increased, especially in Vila Bay. Read More

View Article and Full-Text PDF
September 2021

Single-subject gray matter networks in temporal lobe epilepsy patients with hippocampal sclerosis.

Epilepsy Res 2021 Sep 13;177:106766. Epub 2021 Sep 13.

Department of Radiology, National Center Hospital, National Center of Neurology and Psychiatry, 4-1-1, Ogawa-Higashi, Kodaira, Tokyo, 187-8551, Japan; Cyclotron and Drug Discovery Research Center, Southern TOHOKU Research Institute for Neuroscience, Koriyama, Fukushima, 963-8052, Japan. Electronic address:

Objective: Previous studies have demonstrated structural brain network abnormalities in patients with temporal lobe epilepsy (TLE) using cortical thickness or gray matter (GM) volume. However, no studies have applied single-subject GM network analysis. Here, we first applied an analysis of similarity-based single-subject GM networks to individual patients with TLE. Read More

View Article and Full-Text PDF
September 2021

Design, synthesis and biological evaluation of aminopyrimidine derivatives bearing a 4,5,6,7-tetrahydrothieno [3,2-c]pyridine as potent EGFR inhibitors.

Eur J Med Chem 2021 Sep 11;226:113845. Epub 2021 Sep 11.

Weifang Medical University, No.7166 Baotong Road, Weifang, 261053, PR China. Electronic address:

To resolve the problem of drug resistance caused by epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer, we used the principle of collocation to design and synthesize a series of aminopyrimidine derivatives with 4,5,6,7-tetrahydrothieno [3,2-c]pyridine side chains (according to the binding mode of AZD9291 to EGFR) for use as EGFR kinase inhibitors. The most promising compound A12, a non-covalently bound reversible inhibitor, showed excellent kinase inhibitory activity against EGFR, with an IC value of 4.0 nM and more than 42-fold selectivity for EGFR (IC = 170. Read More

View Article and Full-Text PDF
September 2021

Difference in temporal and spatial distribution pattern of cyanobacteria between the sediment and water column in Lake Chaohu.

Environ Pollut 2021 Sep 11;291:118163. Epub 2021 Sep 11.

State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing, 210008, China. Electronic address:

The evaluation about the relative distribution of cyanobacterial biomass between the sediment and water column would be indispensable to understand if benthic cyanobacteria are important to cyanobacterial biomass in the water column. A separation method for the rapid quantification of benthic cyanobacteria in Lake Chaohu was developed by density-gradient centrifugation. A 2 full factorial design and response surface methodology was employed to optimize the extraction protocol. Read More

View Article and Full-Text PDF
September 2021

Case report of metastatic breast cancer mimicking ileal Crohn's disease.

Int J Surg Case Rep 2021 Sep 14;87:106408. Epub 2021 Sep 14.

Department of Clinical Surgical Sciences, The University of the West Indies, St. Augustine, Trinidad and Tobago.

Introduction: Lobular breast cancer (LBC) has an increased risk of gastrointestinal (GI) spread compared with ductal breast carcinoma. Breast cancer commonly metastasises to bone, lung, liver, central nervous system and rarely to the gastrointestinal tract. As the prognosis for breast cancer continues to improve with modern medical practice it is important to be aware of the various clinical presentations and the appropriate management of breast cancer metastases. Read More

View Article and Full-Text PDF
September 2021

Abdominal cocoon syndrome, a case report of a rare disease entity causing intestinal obstruction.

Int J Surg Case Rep 2021 Sep 13;87:106401. Epub 2021 Sep 13.

Alzaiem Alazhari University - Department of Surgery, Sudan.

Introduction And Importance: Abdominal cocoon syndrome is a rare condition characterized by small bowel encapsulation by a fibrous membrane or a cocoon-like sac. It is an uncommon cause of intestinal obstruction. Less than 300 cases have been reported from all over the world. Read More

View Article and Full-Text PDF
September 2021

Rheological insights on the evolution of sonicated cellulose nanocrystal dispersions.

Ultrason Sonochem 2021 Sep 7;78:105747. Epub 2021 Sep 7.

Research Center for High Performance Polymer and Composite Systems (CREPEC), Department of Chemical Engineering, Polytechnique Montreal, Montreal, Quebec H3C 3A7, Canada. Electronic address:

Cellulose nanocrystals (CNCs) are promising biomaterials, but their tendency to agglomerate when dried limits their use in several applications. Ultrasonication is commonly used to disperse CNCs in water, bringing enough energy to the suspension to break agglomerates. While the optimized parameters for sonication are now well defined for small volumes of low concentration CNC suspensions, a deeper understanding of the influence of the dispersing process is needed to work with larger volumes, at higher concentrations. Read More

View Article and Full-Text PDF
September 2021

Reversing pathology in a preclinical model of Alzheimer's disease by hacking cerebrovascular neoangiogenesis with advanced cancer therapeutics.

EBioMedicine 2021 Sep 14;71:103503. Epub 2021 Sep 14.

Department of Medical Genetics, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada; Michael Smith Laboratories, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada; Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada; The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC V6T 1Z4, Canada; Department of Microbiology and Immunology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z4, Canada; Department of Zoology, University of British Columbia, 6270 University Blvd., Vancouver, BC V6T 1Z4, Canada; The Vancouver Prostate Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC V6T 1Z4, Canada; Department of Urologic Sciences, University of British Columbia, Gordon & Leslie Diamond Health Care Centre, Level 6, 2775 Laurel Street, Vancouver, BC V5Z 1M9, Canada. Electronic address:

Background: Cognitive decline leading to dementia, accompanied by the accumulation of amyloid-beta (Aβ) in neuritic plaques together with the appearance of neurofibrillary tangles (NFT) composed of hyperphosphorylated tau protein (tau), are previously noted hallmarks of Alzheimer's disease (AD). We previously discovered hypervascularity in brain specimens from AD patients and consistent with this observation, we demonstrated that overexpression of Aβ drives cerebrovascular neoangiogenesis leading to hypervascularity and coincident tight-junction disruption and blood-brain barrier (BBB) leakiness in animal models of AD. We subsequently demonstrated that amyloid plaque burden and cerebrovascular pathogenesis subside when pro-angiogenic Aβ levels are reduced. Read More

View Article and Full-Text PDF
September 2021

Insights on the disruption of the complex between human positive coactivator 4 and p53 by small molecules.

Biochem Biophys Res Commun 2021 Sep 10;578:15-20. Epub 2021 Sep 10.

Department of Biophysics, Bose Institute, P-1/12 CIT Scheme VIIM, Kolkata, 700054, India. Electronic address:

Interaction between human positive coactivator 4 (PC4), an abundant nuclear protein, and the tumor suppressor protein p53 plays a crucial role in initiating apoptosis. In certain neurodegenerative diseases PC4 assisted-p53-dependent apoptosis may play a central role. Thus, disruption of p53-PC4 interaction may be a good drug target for certain disease pathologies. Read More

View Article and Full-Text PDF
September 2021

"Feel the fear and do it anyway" … nursing students' experiences of confronting poor practice.

Nurse Educ Pract 2021 Sep 6;56:103196. Epub 2021 Sep 6.

Faculty Head of Education, Faculty of Health, Psychology & Social Care, Manchester Metropolitan University, UK.

Aim: The two aims of this study were, first, to explore nursing students' experiences and perspectives of reporting poor care and second, examine the process by which they raised concerns.

Background: The nursing literature is replete with studies which explore nursing students' experiences of clinical placement. However only a small number explore students experiences of challenging poor care and how this is enacted in the practice setting. Read More

View Article and Full-Text PDF
September 2021

Venomics of the poorly studied hognosed pitvipers Porthidium arcosae and Porthidium volcanicum.

J Proteomics 2021 Sep 14:104379. Epub 2021 Sep 14.

College of Biochemistry and Pharmacy, Faculty of Chemical Sciences, University of Cuenca, Cuenca, Ecuador. Electronic address:

We report the first proteomics analyses of the venoms of two poorly studied snakes, the Manabi hognosed pitviper Porthidium arcosae endemic to the western coastal province of Manabí (Ecuador), and the Costa Rican hognosed pitviper P. volcanicum with distribution restricted to South Pacific Costa Rica and western Panamá. These venom proteomes share a conserved compositional pattern reported in four other congeneric species within the clade of South American Porthidium species, P. Read More

View Article and Full-Text PDF
September 2021

Impact of electrode size and spacing on electrograms: Optimal electrode configuration for near-field electrogram characterization.

Heart Rhythm 2021 Sep 14. Epub 2021 Sep 14.

CHU Bordeaux, IHU LIRYC, Univ. Bordeaux, Bordeaux, France.

Background: Detailed effects of electrode size on EGMs have not been systematically examined.

Objectives: We aimed to elucidate the effect of electrode size on EGMs and investigate an optimal configuration of electrode-size and interelectrode-spacing for gap detection and far-field reduction.

Methods: This study included 8 sheep where probes with different electrode-size and interelectrode-spacing were epicardially placed on healthy, fatty, and lesion tissues for measurements. Read More

View Article and Full-Text PDF
September 2021

Anti-Müllerian hormone, testosterone, and insulin-like peptide 3 as biomarkers of Sertoli and Leydig cell function during deslorelin-induced testicular downregulation in the dog.

Theriogenology 2021 Aug 15;175:100-110. Epub 2021 Aug 15.

Department of Obstetrics and Food Animal Medicine Clinic, University of Veterinary Medicine Budapest, Hungary; ATRC Aurigon Ltd., Dunakeszi, Hungary.

The role of anti-Müllerian hormone (AMH) and insulin-like peptide 3 (INSL3) in male infertility is not fully understood. We used the downregulated testis as a model of gonadotropin-dependent infertility. Serum testosterone and AMH concentrations were studied in five adult male Beagles implanted (day 0) with 4. Read More

View Article and Full-Text PDF

Molecular Subtypes of Primary Small Cell Lung Cancer Tumors and Their Associations with Neuroendocrine and Therapeutic Markers.

J Thorac Oncol 2021 Sep 14. Epub 2021 Sep 14.

Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health. Electronic address:

Introduction: A new molecular subtype classification was recently proposed for small cell lung cancer (SCLC). It is necessary to validate it in primary SCLC tumors by immunohistochemical (IHC) staining and define its clinical relevance.

Methods: We used IHC to assess four subtype markers (ASCL1, NEUROD1, POU2F3, and YAP1) in 194 cores from 146 primary SCLC tumors. Read More

View Article and Full-Text PDF
September 2021

Methods in sulfide and persulfide research.

Nitric Oxide 2021 Sep 14. Epub 2021 Sep 14.

Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan. Electronic address:

Sulfides and persulfides/polysulfides (R-S-R', n > 2; R-S-H, n > 1) are endogenously produced metabolites that are abundant in mammalian and human cells and tissues. The most typical persulfides that are widely distributed among different organisms include various reactive persulfides-low-molecular-weight thiol compounds such as cysteine hydropersulfide, glutathione hydropersulfide, and glutathione trisulfide as well as protein-bound thiols. These species are generally more redox-active than are other simple thiols and disulfides. Read More

View Article and Full-Text PDF
September 2021

Inhibition of c-Jun N-terminal kinase signaling increased apoptosis and prevented the emergence of ALK-TKI-tolerant cells in ALK-rearranged non-small cell lung cancer.

Cancer Lett 2021 Sep 14. Epub 2021 Sep 14.

Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.

Anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) have improved clinical outcomes in non-small cell lung cancer (NSCLC) harboring ALK- rearrangements. However, a small population of tumor cells survives due to adaptive resistance under drug pressure and ultimately acquires drug resistance. Thus, it is necessary to elucidate the mechanisms underlying the prevention of drug resistance to improve the prognosis of patients with ALK-rearranged NSCLC. Read More

View Article and Full-Text PDF
September 2021

The modulatory role of prime identified compounds in Geophila repens in mitigating scopolamine-induced neurotoxicity in experimental rats of Alzheimer's disease via attenuation of cholinesterase, β-secretase, MAPt levels and inhibition of oxidative stress imparts inflammation.

J Ethnopharmacol 2021 Sep 14:114637. Epub 2021 Sep 14.

Regional Plant Resource Centre, Medicinal & Aromatic Plant Division, Forest & Environment Department, Govt. of Odisha, Nayapalli, Bhubaneswar, 751015, India. Electronic address:

Ethnopharmacological Relevance: Geophila repens (L.) I.M. Read More

View Article and Full-Text PDF
September 2021

Itch in Lichen simplex chronicus is associated with localized small fibre neuropathy.

J Invest Dermatol 2021 Sep 14. Epub 2021 Sep 14.

Millennium Nucleus for the Study of Pain (MiNuSPain); Departamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Chile. Electronic address:

View Article and Full-Text PDF
September 2021

Cashing in on ferroptosis against tumor cells: Usher in the next chapter.

Life Sci 2021 Sep 14:119958. Epub 2021 Sep 14.

Burn and Regenerative Medicine Research Center, Velayat Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran; Cardiovascular Diseases Research Center, Department of Cardiology, Heshmat Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran. Electronic address:

Ferroptosis is a new type of non-apoptotic regulated cell death (RCD) driven by unrestricted lethal lipid peroxidation, which is totally distinct from other forms of RCD in genetic and biochemical characteristics. It is generally believed that iron dependency, malfunction of the redox system, and excessive lipid peroxidation are the main hallmarks of ferroptosis. Accumulating pieces of evidence over the past few years have shown that ferroptosis is tightly related to various types of diseases, especially cancers. Read More

View Article and Full-Text PDF
September 2021

Kidney toxicity of the BRAF-kinase inhibitor vemurafenib is driven by off-target ferrochelatase inhibition.

Kidney Int 2021 Sep 14. Epub 2021 Sep 14.

Division of Pharmaceutics and Pharmacology, College of Pharmacy & Comprehensive Cancer Center, Ohio State University, Columbus, OH, USA. Electronic address:

A multitude of disease and therapy related factors drive the frequent development of kidney disorders in cancer patients. Along with chemotherapy, the newer targeted therapeutics can also cause kidney dysfunction through on and off-target mechanisms. Interestingly, among the small molecule inhibitors approved for the treatment of cancers that harbor BRAF-kinase activating mutations, vemurafenib can trigger tubular damage and acute kidney injury. Read More

View Article and Full-Text PDF
September 2021

7-[[(4-methyl-2-pyridinyl)amino](2-pyridinyl)methyl]-8-quinolinol (compound 30666) inhibits enhancer activity and reduces B-cell lymphoma growth - A question of specificity.

Eur J Pharmacol 2021 Sep 14:174505. Epub 2021 Sep 14.

Institute of Human Genetics, Polish Academy of Sciences, Poznań, Poland. Electronic address:

B-cell non-Hodgkin lymphoma (NHL) is among the ten most common malignancies. Survival rates range from very poor to over 90% and highly depend on the stage and subtype. Characteristic features of NHL are recurrent translocations juxtaposing an oncogene (e. Read More

View Article and Full-Text PDF
September 2021

Similar Ferroportin Q248H polymorphism prevalence in patients with Plasmodium falciparum malaria and control subjects in the low-endemic setting of Botswana.

Clin Chim Acta 2021 Sep 14. Epub 2021 Sep 14.

School of Allied Health Professions, Faculty of Health Sciences, University of Botswana, Gaborone, Botswana. Electronic address:

Introduction: Recent evidence suggests that ferroportin (FPN) Q248H may confer a survival advantage against malaria by reducing erythrocytic intracellular iron in Africans. We investigated if FPN Q248H mutation, that is prevalent in Batswana, is a factor in limiting the susceptibility to Plasmodium falciparum malaria.

Methods: 264 archived dried blood spot samples (183 P. Read More

View Article and Full-Text PDF
September 2021

Acalabrutinib, venetoclax, and obinutuzumab as frontline treatment for chronic lymphocytic leukaemia: a single-arm, open-label, phase 2 study.

Lancet Oncol 2021 Sep 14. Epub 2021 Sep 14.

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Background: Both continuous therapy with acalabrutinib and fixed-duration therapy with venetoclax-obinutuzumab are effective for previously untreated chronic lymphocytic leukaemia. We hypothesised that frontline time-limited, minimal residual disease (MRD)-guided triplet therapy with acalabrutinib, venetoclax, and obinutuzumab would induce deep (ie, more patients with undetectable MRD) and durable remissions.

Methods: In this open-label, single-arm, investigator-sponsored, phase 2 study, patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma were recruited from two academic hospitals in Boston, MA, USA. Read More

View Article and Full-Text PDF
September 2021

Efficacy and factors affecting procedure results of short-type single-balloon enteroscopy-assisted ERCP for altered anatomy: a multicenter cohort in JAPAN.

Gastrointest Endosc 2021 Sep 14. Epub 2021 Sep 14.

Department of Gastroenterology, Kitasato University of Medicine.

Background And Aims: Although single-balloon enteroscopy (SBE)-assisted or short-type SBE (short SBE)-assisted endoscopic retrograde cholangiopancreatography (ERCP) has been reported as useful in patients with surgically altered anatomy, most of the studies had small sample sizes or single-center designs. This study aimed to evaluate the efficacy and factors affecting the procedure results of short SBE-assisted ERCP in patients with surgically altered anatomy.

Methods: This multicenter retrospective study was conducted at 8 tertiary referral care centers in Japan. Read More

View Article and Full-Text PDF
September 2021

Action-based organization of a cerebellar module specialized for predictive control of multiple body parts.

Neuron 2021 Sep;109(18):2981-2994.e5

Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address:

The role of the cerebellum in predictive motor control and coordination has been thoroughly studied during movements of a single body part. In the real world, however, actions are often more complex. Here, we show that a small area in the rostral anterior interpositus nucleus (rAIN) of the mouse cerebellum is responsible for generating a predictive motor synergy that serves to protect the eye by precisely coordinating muscles of the eyelid, neck, and forelimb. Read More

View Article and Full-Text PDF
September 2021