Categorical misalignment: Making autism(s) in big data biobanking.

The opaque relationship between biology and behavior is an intractable problem for psychiatry, and it increasingly challenges longstanding diagnostic categorizations. While various big data sciences have been repeatedly deployed as potential solutions, they have so far complicated more than they have managed to disentangle. Attending to , this article proposes one reason why this is the case: Datasets have to instantiate clinical categories in order to make biological sense of them, and they do so in different ways.

A machine learning strategy for the identification of key descriptors and prediction models for IgG monoclonal antibody developability properties.

Identification of favorable biophysical properties for protein therapeutics as part of developability assessment is a crucial part of the preclinical development process. Successful prediction of such properties and bioassay results from calculated features has potential to reduce the time and cost of delivering clinical-grade material to patients, but nevertheless has remained an ongoing challenge to the field. Here, we demonstrate an automated and flexible machine learning workflow designed to compare and identify the most powerful features from computationally derived physiochemical feature sets, generated from popular commercial software packages.

Design of a mucin-selective protease for targeted degradation of cancer-associated mucins.

Targeted protein degradation is an emerging strategy for the elimination of classically undruggable proteins. Here, to expand the landscape of targetable substrates, we designed degraders that achieve substrate selectivity via recognition of a discrete peptide and glycan motif and achieve cell-type selectivity via antigen-driven cell-surface binding. We applied this approach to mucins, O-glycosylated proteins that drive cancer progression through biophysical and immunological mechanisms.

Comparison of combined substrate-based mapping techniques to identify critical sites for ventricular tachycardia ablation.

Background: Established electroanatomic mapping techniques for substrate mapping for ventricular tachycardia (VT) ablation includes voltage mapping, isochronal late activation mapping (ILAM), and fractionation mapping. Omnipolar mapping (Abbott Medical, Inc.) is a novel optimized bipolar electrogram creation technique with integrated local conduction velocity annotation.

Does Aspirin Provide Adequate Chemoprophylaxis for Venous Thromboembolic Events in Operative Pelvic and Acetabular Fractures?

Background: Several strategies exist to prevent venous thromboembolism (VTE) in operative pelvic and acetabular fractures, however literature lacks consensus on the optimal thromboprophylaxis. Even more debated, and perhaps controversial, is whether aspirin provides adequate thromboprophylaxis in the setting of these injuries. The primary objective was to evaluate the efficacy of aspirin in the prevention of venous thromboembolism (VTE) events, including deep vein thrombosis (DVT) and pulmonary embolism (PE) in operative pelvic and acetabular fractures compared to other anticoagulants.

What are the predictors of TOMM failure in clinical TBI populations? A retrospective analysis.

Objectives: To determine base rates of invalid performance on the Test of Memory Malingering (TOMM) in patients with traumatic brain injury (TBI) undertaking rehabilitation who were referred for clinical assessment, and the factors contributing to TOMM failure.

Methods: Retrospective file review of consecutive TBI referrals for neuropsychological assessment over seven years. TOMM failure was conventionally defined as performance <45/50 on Trial 2 or Retention Trial.

Immunosuppressive glycoproteins associate with breast tumor fibrosis and aggression.

Tumors feature elevated sialoglycoprotein content. Sialoglycoproteins promote tumor progression and are linked to immune suppression via the sialic acid-Siglec axis. Understanding factors that increase sialoglycoprotein biosynthesis in tumors could identify approaches to improve patient response to immunotherapy.

Sphenoid sinusitis: a rare cause of ischaemic stroke.

We present the case of a 61-year-old woman who presented to the accident and emergency department with an ischaemic stroke, on a background of receiving intravenous and oral antibiotics to treat chronic left sphenoid sinusitis. Initially presenting with right-sided weakness and aphasia, a diagnosis of acute ischaemic stroke was made. Antibiotics had been commenced 1 month prior to the ischaemic stroke.

Associations Between Ambient Particulate Air Pollution and Cognitive Function in Indonesian Children Living in Forest Fire-Prone Provinces.

Smoke from forest fires can reach hazardous levels for extended periods of time. We aimed to determine if there is an association between particulate matter ≤2.5 µm in aerodynamic diameter (PM) and living in a forest fire-prone province and cognitive function.

Leveraging microenvironmental synthetic lethalities to treat cancer.

Treatment resistance leads to cancer patient mortality. Therapeutic approaches that employ synthetic lethality to target mutational vulnerabilities in key tumor cell signaling pathways have proven effective in overcoming therapeutic resistance in some cancers. Yet, tumors are organs composed of malignant cells residing within a cellular and noncellular stroma.

Synthetic Tuning of Domain Stoichiometry in Nanobody-Enzyme Megamolecules.

This paper presents a method to synthetically tune atomically precise megamolecule nanobody-enzyme conjugates for prodrug cancer therapy. Previous efforts to create heterobifunctional protein conjugates suffered from heterogeneity in domain stoichiometry, which in part led to the failure of antibody-enzyme conjugates in clinical trials. We used the megamolecule approach to synthesize anti-HER2 nanobody-cytosine deaminase conjugates with tunable numbers of nanobody and enzyme domains in a single, covalent molecule.

Concepts of extracellular matrix remodelling in tumour progression and metastasis.

Tissues are dynamically shaped by bidirectional communication between resident cells and the extracellular matrix (ECM) through cell-matrix interactions and ECM remodelling. Tumours leverage ECM remodelling to create a microenvironment that promotes tumourigenesis and metastasis. In this review, we focus on how tumour and tumour-associated stromal cells deposit, biochemically and biophysically modify, and degrade tumour-associated ECM.

A Conditional Mutation in Reveals Linkage Between PIN Protein Trafficking, Auxin Transport, Gravitropism, and Lateral Root Initiation.

Auxin is transported in plants with distinct polarity, defined by transport proteins of the PIN-formed (PIN) family. Components of the complex trafficking machinery responsible for polar PIN protein localization have been identified by genetic approaches, but severe developmental phenotypes of trafficking mutants complicate dissection of this pathway. We utilized a temperature sensitive allele of () that encodes a RAB-guanine nucleotide exchange factor.

Comparison of Infrapatellar and Suprapatellar Approaches for Intramedullary Nail Fixation of Tibia Fractures.

Objective: To assess clinical, radiographic, and functional outcomes after intramedullary nail (IMN) fixation of tibia fractures with an infrapatellar approach compared to a suprapatellar approach.

Design: Retrospective chart review.

Setting: Level 1 trauma center.

Clinical Outcomes After Intramedullary Nailing of Intraarticular Distal Tibial Fractures: A Retrospective Review.

Unlabelled: The objective of this study was to evaluate the clinical and functional outcomes of intra-articular distal tibial fractures after intramedullary nail (IMN) and independent fixation compared with extra-articular fracture controls.

Methods: A retrospective chart review of distal tibial fractures treated with IMN was performed. Clinical outcomes were compared between fractures with and without intra-articular involvement.

Primary Triple Arthrodesis Equivalent for Complete Extruded Missing Talus with Associated Midfoot Instability: A Case Report.

Case: Complete extrusion of the talus is rare and associated with high rates of complications including infection, osteonecrosis, persistent pain and stiffness, and post-traumatic arthritis. Less well described is associated midfoot instability. We report a case of a complete extruded missing talus that resulted in significant midfoot instability treated with a modified triple arthrodesis of the tibiocalcaneal, tibionavicular, and calcaneocuboid joints.

Role of Lipopolysaccharide in Protecting OmpT from Autoproteolysis during In Vitro Refolding.

Outer membrane protease (OmpT) is a 33.5 kDa aspartyl protease that cleaves at dibasic sites and is thought to function as a defense mechanism for against cationic antimicrobial peptides secreted by the host immune system. Despite carrying three dibasic sites in its own sequence, there is no report of OmpT autoproteolysis in vivo.

Physical Activity for Bone Health: How Much and/or How Hard?

Purpose: High-impact physical activity is associated with bone health, but higher volumes of lower-intensity activity may also be important. The aims of this study were to: 1) investigate the relative importance of volume and intensity of physical activity accumulated during late adolescence for bone health at age 23 yr; and 2) illustrate interpretation of the results.

Methods: This is a secondary analysis of data from the Iowa Bone Development Study, a longitudinal study of bone health from childhood through to young adulthood.

Perinatal complications are associated with social anxiety: Indirect effects through temperament.

The current investigation examines the relation between perinatal complications and social anxiety incorporating the potential indirect effect of child temperament. Participants were 149 children 9 to 12 years of age (M=9.97, SD=1.

An 8-Year Longitudinal Analysis of Physical Activity and Bone Strength From Adolescence to Emerging Adulthood: The Iowa Bone Development Study.

Purpose: Most pediatric physical activity and bone health research has focused on the period immediately around puberty; few have addressed bone structural strength outcomes. This study assessed the magnitude and consistency of the longitudinal relationships between device-measured vigorous-intensity physical activity (VPA) and structural bone strength outcomes across adolescence to emerging adulthood.

Methods: Participants with 3 to 5 bone scans between the age of 11 and 19 years were studied (N = 439, 220 females, 1838 records).

Comparison of Clinical Outcomes After Intramedullary Fixation of Tibia Fractures Caused by Blunt Trauma and Civilian Gunshot Wounds: A Retrospective Review.

Objective: To assess the outcomes of patients who sustained blunt trauma tibia fractures compared with tibia fractures from civilian gunshot injuries when treated with intramedullary fixation.

Design: Retrospective chart review.

Setting: Level I trauma center.

Damage to or Injury of the Distal Semitendinosus Tendon During Sporting Activities: A Systematic Review.

Background: Isolated distal semitendinosus tears and avulsions sustained during sporting activities are uncommon.

Question/purposes: We sought to systematically review the literature to identify athletes sustaining distal semitendinosus tears and avulsions during sporting activities and to better understand injury mechanisms, management, and return-to-sport timing.

Methods: PubMed, Biosis Previews, SPORTDiscus, PEDro, and EMBASE databases were searched from January 1970 to January 2018 using the search terms , , , , , , and .