ATI-50001 / Aclaris, Rigel - LARVOL DELTA

The Relative Efficacy and Safety of Monotherapies for Alopecia Areata: A Network Meta-Analysis Study. (PubMed, J Cosmet Dermatol) - "We produced high-quality evidence on the comparative effectiveness of monotherapies for AA with various regimens of 8 JAKIs, including the FDA-approved ones. Our findings can improve clinicians' decision-making and update guidelines for medical practice."

Clinical • Journal • Retrospective data • Review • Alopecia • Immunology

Bioinspired Total Synthesis and Biological Evaluation of Nucleoside Antibiotics A201E and the Derivatives of A201 Family. (PubMed, J Org Chem) - "A comprehensive assessment of their antimicrobial activities has illuminated the structure-activity relationship of A201A/E and its analogues. The synthetic strategy we report herein will guide the creation of additional analogues, potentially elucidating the mode of action and addressing a critical area of unmet medical need."

Journal

3D Resin-coated pressure sensor response for bite force assessment: A pilot study. (PubMed, J Dent Res Dent Clin Dent Prospects) - "In this preliminary study, the evaluated sensor (FlexiForce A201 Sensor, Tekscan) was firstly calibrated without any type of cover material, and later tested with 3D printing resin with different thicknesses (1 mm, 1.15 mm, 1.4 mm and 1.6 mm)...When the pressure sensor was covered with resin of 1mm and 1.6 mm thick specimens, a higher difference was found between the applied load and the corresponding sensor reading. It was concluded that it is possible to use this type of pressure sensor and that it showed better accuracy with the 1.15 mm and 1.4 mm 3D printing resin covering."

Journal • Dental Disorders

First-in-human Study of OT-A201 in Patients With Selected Hematological Malignancies and Solid Tumors (clinicaltrials.gov) - P1 | N=150 | Recruiting | Sponsor: Onward Therapeutics | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Monotherapy • Hematological Disorders • Hematological Malignancies • Oncology • Solid Tumor

First-in-human Study of OT-A201 in Patients With Selected Hematological Malignancies and Solid Tumors (clinicaltrials.gov) - P1 | N=150 | Not yet recruiting | Sponsor: Onward Therapeutics

Combination therapy • Monotherapy • New P1 trial • Hematological Disorders • Hematological Malignancies • Oncology • Solid Tumor

Diastolic versus Systolic Left Ventricular Dysfunction as Independent Predictors for Unfavorable Postoperative Evolution in Patients with Aortic Regurgitation Undergoing Aortic Valve Replacement. (PubMed, Medicina (Kaunas)) - "Materials and We performed a prospective study enrolling 332 AR patients undergoing AVR, divided into two groups: Group A-201 pts with normal LV systolic function, divided into two subgroups (A1: 129 pts with a nonrestrictive LVDFP and A2: 72 pts with restrictive LVDFP), and Group B-131 pts with LV systolic dysfunction (LV ejection fraction LVEF < 50%), divided into two subgroups (B1: 83 pts with a nonrestrictive LVDFP and B2: 48 pts with restrictive LVDFP)...The LV diastolic function is a more reliable parameter for prognosis than LV systolic performance (RR 9.2 versus 2.1). Other independent predictors for increased early postoperative mortality rate were: an age > 75 years, an LVESD > 58 mm, and comorbidities (diabetes mellitus, COPD), and for unfavorable evolution at 2 years postoperatively: an age > 75 years, an LVESV > 95 cm, and severe pulmonary hypertension."

Journal • Cardiovascular • Chronic Obstructive Pulmonary Disease • Diabetes • Heart Failure • Hypertension • Immunology • Metabolic Disorders • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Total Synthesis of Complex Nucleoside Antibiotics: Bioinspired Total Syntheses of Nucleoside Antibiotics A201A, A201D and A201E. (PubMed, Angew Chem Int Ed Engl) - "This modular synthesis strategy enables efficient preparation of A201 family antibiotics, allowing the study of their structure-activity relationships and mode of action. This study satisfies the increasing demand for developing novel antibiotics inspired by the A201 family."

Journal

First-in-Human Assessment of Feasibility and Safety of Multiplexed Genetic Engineering of Autologous T Cells Expressing NY-ESO -1 TCR and CRISPR/Cas9 Gene Edited to Eliminate Endogenous TCR and PD-1 (NYCE T cells) in Advanced Multiple Myeloma (MM) and Sarcoma (ASH 2019) - P1; "An HLA-A201 restricted TCR recognizing the NY-ESO-1/LAGE-1 157-165 epitope (SLLMWITQC) kills NY-ESO positive cell lines and has been used to treat 25 patients with MM after ASCT with expansion, persistence, antigen-directed functionality and long-term safety and antitumor activity (Nat Med 2015, Blood Adv 2019)...Once cells were successfully manufactured and released, pts received fludarabine 30mg/m2 and cyclophosphamide 300mg/m2 daily on day -4,-3,-2...Pt 1 is a 67 y/o F with IgG kappa MM with lytic bone lesions, and a +17q after 8 lines of therapy including 3 ASCTs, lenalidomide, pomalidomide, bortezomib, carfilzomib, daratumumab, and panobinostat. Pt 2 is a 65 y/o M with a recurrent MRCL manifested by abdominal and pelvic involvement after neo-adjuvant doxorubicin, multiple resections and radiation treatments with progression at time of enrollment... Early results of a phase 1 trial of NYCE T cells infused in 3 pts with advanced MM and MRCL show safety and feasibility..."

Clinical • IO biomarker • P1 data • Melanoma • Multiple Myeloma • Oncology • Plasmacytoma • Sarcoma • CTAG2 • PD-1 • PD-L1

HapticLink: A Force-based Haptic Feedback System for Single and Double Lower-Limb Amputees. (PubMed, Annu Int Conf IEEE Eng Med Biol Soc) - "The FlexiForce A201 sensors were identified as the optimal choice for the parameters and scenarios investigated...94.44, 79.17%, and 100%) and responses from the participants indicating that HapticLink may aid during single or double lower-limb amputee ambulation after establishing haptic feedback intensity comfort. Finally, the successful qualitative tests with a double lower-limb amputee imply the haptic feedback may be sufficient without requiring sensor fusion on the part of the participant from both the VMs and the proprioception of the contralateral leg. Clinical Relevance--- This establishes the utility of a simple, stand-alone 4:4 force sensor and haptic motor feedback system to aid during single or double lower-limb amputee ambulation."

Journal

Effect of Natural Aging on the Stress Corrosion Cracking Behavior of A201-T7 Aluminum Alloy. (PubMed, Materials (Basel)) - "Natural aging after quenching is essential to improve the alloy's resistance to SCC. It might be due to the prevention of the formation of the precipitation free zone (PFZ) after T7 tempering."

Journal

Design of Pressure Sensor Arrays to Assess Electrode Contact Pressure During In Vivo Recordings in the Gut. (PubMed, Annu Int Conf IEEE Eng Med Biol Soc) - "Commercially available FlexiForce A201 sensors were used to compare to the Velostat-based sensors...Simultaneous pressure and slow wave recordings were performed in vivo on a rabbit small intestine. The Velostat-based sensors were able to resolve spatiotemporal changes in contact pressure in the range of 0-10 000 Pa."

Journal • Preclinical • Gastrointestinal Disorder

Reduced neuronal sensitivity and susceptibility of the fall armyworm, Spodoptera frugiperda, to pyrethroids in the absence of known knockdown mutations. (PubMed, Pestic Biochem Physiol) - "For acetylcholinesterase, FAW had more than 80% of their nucleotide sequences consistent with A201 and F290 of the susceptible strains although 60% of the tested population was heterozygous for the G227A mutation...Additionally, these data suggest the kdr phenotype only explains a portion of the heritable variation in FAW resistance and indicates kdr is not the only predictor of high pyrethroid resistance. Phenotypic assays, such as toxicity bioassays or neurophysiological recordings, using field-collected populations are necessary to reliably predict resistant phenotypes and product failures."

Journal

[VIRTUAL] Design of Pressure Sensor Arrays to Assess Electrode Contact Pressure During in Vivo Recordings in the Gut (EMBC 2020) - "Commercially available FlexiForce A201 sensors were used to compare to the Velostat-based sensors...Simultaneous pressure and slow wave recordings were performed in vivo on a rabbit small intestine. The Velostat-based sensors were able to resolve spatiotemporal changes in contact pressure in the range of 0–10,000 Pa."

Preclinical

Biomechanical comparison of three different compression screws for treatment of odontoid fractures evaluation of a new screw design. (PubMed, Clin Biomech (Bristol, Avon)) - "Double-threaded screw is robust against screw stripping, but achieves only low fragment compression. The classic compression screws achieve better compression, but are sensitive to screw stripping. Sleeve-nut screw is superior in compression and as robust as double-threaded screw against screw stripping. Whether the better biomechanical properties lead to a reduction in pseudarthrosis must be proven in clinical trials."

Journal • Musculoskeletal Diseases

[VIRTUAL] Does probiotic microorganism lactobacillus reuteri prevents allergic rhinitis and rhinoconjunctivitis development in children (EAACI 2020) - "According to the addition of LR in to the child diet children were divided in two groups: group A-201 infants exclusively breastfed for 4-6 months and group B-115 infants breastfed with addition of L. reuteri from fourth week of life for 12 weeks... The study confirms that addition of LR to early childs diet has beneficial effect on the occurrence and course of AR but not of ARC."

Clinical • Allergic Rhinitis • Allergy • Immunology

Genotyping Can Resolve Group A Subtype Discrepancies and Increase Pool of Non-A1 Donors for ABO-Incompatible Organ Transplantation (AABB 2019) - "Genomic sequencing of exons 6 and 7 confirmed A2/A2, specifically ABO*A201/A201 (467T and 1061 deleted C); no changes from conventional were found by full gene sequencing... Due to the A subgroup typing discrepancy, this donor’s scheduled donation to an O blood type recipient (part of an internal liver transplant chain) was canceled and the donor’s left lobe was transplanted to a group A recipient. Standardization of anti-A1 lectin reagents is based on RBC phenotype of non-A1 donors. It is unclear if gene dose effects contribute to differences between reagents or if greater reactivity is seen in A2 homozygous versus A2 heterozygous donors."

Mapping and Functional Characterization of Proteolytic Cleavage of Murine Kidney Injury Molecule 1 (KIDNEY WEEK 2019) - "Methods Based on common structural motifs involved in TACE and ADAM10 recognition of substrates, we mapped out a potential cleavage site between A201 and I202 within the predicted cleavage region T194 to I202...ADAM10-mediated KIM-1 shedding is required for efficient efferocytosis. Funding Government Support - Non-U.S."

Preclinical

Use of an Errorless Learning Approach in a Person With Concomitant Traumatic Spinal Cord Injury and Brain Injury: A Case Report. (PubMed, J Neurol Phys Ther) - "Errorless learning may have facilitated acquisition of novel transfer and mobility skills in this individual with dual diagnoses. This approach may have value for patients with neurologic conditions who have both motor and cognitive impairment.Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A201)."

Clinical • Journal

ATI-501 Oral Suspension Compared to Placebo in Subjects With Alopecia Areata, Alopecia Universalis or Alopecia Totalis (clinicaltrials.gov) - P2; N=87; Completed; Sponsor: Aclaris Therapeutics, Inc.; Active, not recruiting ➔ Completed

Clinical • Trial completion

CD39+CD8+ T cells exhibit a distinct phenotype among tumor-infiltrating tumor-antigen-specific CD8+ T cells (AAI 2019) - "...To identify tumor antigen-specific CD8+ T cells, we used 11 HLA-A*A201 multimers specific for tumor associated antigens, including MAGE A1, NY-ESO-1, and AFP...In addition, CD39+CD8+ T cells expressed higher levels of tissue residency markers, such as CD103 and CD69. In conclusion, CD39+CD8+ T cells exhibit distinct phenotypes that represent severe exhaustion and terminal differentiation among tumor-infiltrating tumor-antigen-specific CD8+ T cells"