Survival with Trastuzumab Emtansine in Residual HER2-Positive Breast Cancer.

Background: Patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer with residual invasive disease after neoadjuvant systemic therapy have a high risk of recurrence and death. The primary analysis of KATHERINE, a phase 3, open-label trial, showed that the risk of invasive breast cancer or death was 50% lower with adjuvant trastuzumab emtansine (T-DM1) than with trastuzumab alone.

Methods: We randomly assigned patients with HER2-positive early breast cancer with residual invasive disease in the breast or axilla after neoadjuvant systemic treatment with taxane-based chemotherapy and trastuzumab to receive T-DM1 or trastuzumab for 14 cycles.

Fracture Prevention with Infrequent Zoledronate in Women 50 to 60 Years of Age.

Background: Zoledronate prevents fractures in older women when administered every 12 to 18 months, but its effects on bone density and bone turnover persist beyond 5 years. Whether infrequent zoledronate administration would prevent vertebral fractures in early postmenopausal women is unknown.

Methods: We conducted a 10-year, prospective, double-blind, randomized, placebo-controlled trial involving early postmenopausal women (50 to 60 years of age) with bone mineral density T scores lower than 0 and higher than -2.

Development of a Novel Human Serum Albumin-Based Tool for Effective Drug Discovery: The Investigation of Protein Quality and Immobilization.

The binding ability of human serum albumin (HSA) on active pharmaceutical ingredients (APIs) is one of the most important parameters in the early stages of drug discovery. In this study, an immobilized HSA-based tool was developed for the rapid and easy in vitro screening of API binding. The work explored the serious incompleteness in the identification of HSA used for in vitro screening published in the last five years.

Design of an Ultrafast and Controlled Visible Light-Mediated Photoiniferter RAFT Polymerization for Polymerization-Induced Self-Assembly (PISA).

In this contribution, we designed a new xanthate RAFT agent by introducing (5,6,7,8-tetrahydro-2-naphthalenyl)oxy (TNO) as the Z group, namely 2-[(((5,6,7,8-Tetrahydro-2-naphthalenyl)oxycarbonothioyl)thio)ethyl propanoate] (TNXEP). Due to the presence of the TNO group, TNXEP enabled highly controlled and ultrafast photoiniferter RAFT polymerization under violet (λ = 405 nm) and blue (λ = 450 nm) light. This approach was effectively extended to aqueous media for polymerization-induced self-assembly (PISA), facilitating the synthesis of polymeric nanoparticles.

Anchoring of Probiotic-Membrane Vesicles in Hydrogels Facilitates Wound Vascularization.

Inadequate vascularization significantly hampers wound recovery by limiting nutrient delivery. To address this challenge, we extracted membrane vesicles from (LMVs) and identified their angiogenic potential via transcriptomic analysis. We further developed a composite hydrogel system (Gel-LMVs) by anchoring LMVs within carboxylated chitosan and cross-linking it with oxidized hyaluronic acid through a Schiff base reaction.

Child Neurology: Severe -Related Congenital Muscular Dystrophy With Rapidly Progressive Encephalopathy Leading to Infantile Death.

Pathogenic variants in cause congenital muscular dystrophy through hypoglycosylation of alpha-dystroglycan (OMIM #615350). The established phenotypic spectrum of GMPPB-related disorders includes recurrent rhabdomyolysis, limb-girdle muscular dystrophy, neuromuscular transmission abnormalities, and congenital muscular dystrophy with variable brain and eye anomalies. We report a 9-month-old male infant with congenital muscular dystrophy, infantile spasms, and compound heterozygous pathogenic variants (c.

Sex Differences in Natural History and Health Outcomes Among Individuals With Tic Disorders.

Objectives: To analyze sex differences in outcomes in Tourette syndrome (TS) and Persistent Motor or Vocal tic disorders (PMVT) in the Tourette Association of America International Consortium for Genetics (TAAICG) dataset.

Methods: The relationship between sex and clinical measures was explored in 2,403 participants (N = 2,109 with TS; N = 294 with PMVT) from the TAAICG dataset using generalized estimating equation regression models, and adjusted for age and family relationships.

Results: Female (vs male) participants with TS (25.

α-Actinin-1 deficiency in megakaryocytes causes low platelet count, platelet dysfunction, and mitochondrial impairment.

Cytoskeletal remodeling and mitochondrial bioenergetics play important roles in thrombocytopoiesis and platelet function. Recently, α-actinin-1 mutations have been reported in patients with congenital macrothrombocytopenia. However, the role and underlying mechanism of α-actinin-1 in thrombocytopoiesis and platelet function remain elusive.

Current developments in T-cell receptor therapy for Acute Myeloid Leukaemia.

T-cell receptor (TCR) therapies are a promising modality for the treatment of cancers, with significant efforts being directed towards acute myeloid leukaemia (AML), a particularly challenging disease. Chimeric antigen receptor (CAR) T-cells targeting single surface antigens have shown remarkable efficacy for B-cell lymphoblastic leukaemia, lymphomas and multiple myeloma. However, AML presents formidable obstacles to the effectiveness of CAR T-cells due to the widespread expression of heterogenous leukaemia immunophenotypes and surface antigen targets additionally present on normal myeloid cells.

Identification of possible drug treatment targets and related immune cell infiltration properties in acute myeloid leukemia utilizing robust rank aggregation algorithm.

In this study, we aimed to uncover novel biomarkers in acute myeloid leukemia (AML) that could serve as prognostic indicators or therapeutic targets. We analyzed AML microarray datasets from the Gene Expression Omnibus (GEO) repository, identifying key differentially expressed genes (DEGs) through the robust rank aggregation (RRA) approach. The functions of these DEGs were elucidated through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses.

Review of Outcomes After Peripheral Nerve Transfers for Motor Nerve Injury in the Upper Extremity.

Background: Modern nerve-to-nerve transfers are a significant advancement in peripheral nerve surgery. Nerve transfers involve transferring donor nerves or branches to recipient nerves close to the motor end unit, leading to earlier reinnervation and preservation of the musculotendinous units in proximal nerve injuries. After nerve reinnervation, function may be superior to traditional tendon transfer techniques in terms of strength and independent motion.

Quantitative Analysis of Multi-Elements in a Micron-Sized Single Particle Based on Laser-Induced Breakdown Spectroscopy Signal Enhancement of an Optical Fiber Collimated System.

With rapid, energy-intensive, and coal-fueled economic growth, global air quality is deteriorating, and particulate matter pollution has emerged as one of the major public health problems worldwide. It is extremely urgent to achieve carbon emission reduction and air pollution prevention and control, aiming at the common problem of weak and unstable signals of characteristic elements in the application of laser-induced breakdown spectroscopy (LIBS) technology for trace element detection. In this study, the influence of the optical fiber collimation signal enhancement method on the LIBS signal was explored.