The Functional Transcriptomic Landscape Informs Therapeutic Strategies in Multiple Myeloma.

Several therapeutic agents have been approved for treating multiple myeloma, a cancer of bone marrow-resident plasma cells. Predictive biomarkers for drug response could help guide clinical strategies to optimize outcomes. In this study, we present an integrated functional genomic analysis of tumor samples from patients multiple myeloma that were assessed for their ex vivo drug sensitivity to 37 drugs, clinical variables, cytogenetics, mutational profiles, and transcriptomes.

Minimally invasive technique for acute fixation and subtalar fusion of displaced intra-articular calcaneus fractures.

Displaced intra-articular calcaneus fractures (DIACFs) are difficult injuries to treat and are often encountered by orthopedic surgeons. For DIACFs treated nonoperatively or with open reduction internal fixation (ORIF), a common complication is painful subtalar arthritis and the need for a secondary subtalar fusion, which prolongs the overall recovery time. One treatment option to address this sequela involves ORIF with subtalar fusion as the primary treatment.

Functional quality of life among newly diagnosed young adult colorectal cancer survivors compared to older adults: results from the ColoCare Study.

Purpose: Colorectal cancer (CRC) incidence and mortality are increasing among young adults (YAs) aged 18-39. This study compared quality of life (QOL) between YA and older adult CRC survivors in the ColoCare Study.

Methods: Participants were grouped by age (years) as follows: 18-39 (YA), 40-49, 50-64, and 65 + .

Implementation of required sedation assessment in nursing workflow to address naloxone utilization.

Objective: Opioid-related adverse drug events continue to occur. This study aimed to characterize the patient population receiving naloxone to inform future intervention efforts.

Design: We describe a case series of patients who received naloxone in the hospital during a 16-week time frame in 2016.

Detectable Lipidomes and Metabolomes by Different Plasma Exosome Isolation Methods in Healthy Controls and Patients with Advanced Prostate and Lung Cancer.

Circulating exosomes in the blood are promising tools for biomarker discovery in cancer. Due to their heterogeneity, different isolation methods may enrich distinct exosome cargos generating different omic profiles. In this study, we evaluated the effects of plasma exosome isolation methods on detectable multi-omic profiles in patients with non-small cell lung cancer (NSCLC), castration-resistant prostate cancer (CRPC), and healthy controls, and developed an algorithm to quantify exosome enrichment.

Balancing Safety, Comfort, and Fall Risk: An Intervention to Limit Opioid and Benzodiazepine Prescriptions for Geriatric Patients.

Introduction: This study reports on the impact of a clinical decision support tool embedded in the electronic medical record and characterizes the demographics, prescribing patterns, and risk factors associated with opioid and benzodiazepine misuse in the older adult population.

Significance: This study reports on prescribing patterns for patients ≥65 years-old who presented to Emergency Departments (ED) or Urgent Care (UC) facilities across a large healthcare system following a fall (n = 34,334 encounters; n = 25,469 patients). This system implemented a clinical decision support intervention which provides an alert when the patient has an evidence-based risk factor for prescription drug misuse; prescribers can continue, amend or cancel the prescription.

Factors associated with self-reported social isolation among patients with cancer during the COVID-19 pandemic.

Objective: We aimed to identify patient-level demographic and behavioral characteristics associated with higher social isolation among patients with cancer throughout the coronavirus disease 2019 (COVID-19) pandemic.

Method: Moffitt Cancer Center patients seen on or after January 1, 2015, had a last known alive vital status, a valid e-mail address, and were 18-89 years old, were emailed a survey regarding social isolation. We collected information on age, sex, race, ethnicity, marital status, smoking, self-reported cancer diagnosis, cancer treatment, and perceived life changes due to the COVID-19 pandemic.

Hold the Antibiotics: Are Preoperative Antibiotics Unnecessary in the Treatment of Pediatric Supracondylar Humerus Fractures?

Background: Supracondylar humerus (SCH) fracture is the most common elbow injury in children and often treated with closed reduction and percutaneous pinning (CRPP). There is little published evidence supporting or refuting the use of perioperative prophylactic antibiotics for SCH CRPP in the pediatric population. The purpose of this study is to evaluate the rate of surgical site infection for patients with and without preoperative antibiotics.

Screws-Only Primary Subtalar Arthrodesis for Calcaneus Fractures.

Background: The management of displaced intraarticular calcaneus fractures (DIACFs) is a difficult problem with disappointing results from open reduction internal fixation (ORIF). Alternatively, ORIF with primary subtalar arthrodesis (PSTA) has gained increasing popularity. The purpose of this study is to review patient-centered and radiographic outcomes of ORIF plus PSTA using only screws through a sinus tarsi approach.

Modifying Interhospital Hepatopancreatobiliary Transfers Based on Predictive Analytics: Moving from a Center of Excellence to a Health-Care System of Excellence.

Regionalization of complex surgical care has increased interhospital transfers to quaternary centers within large health-care systems. Risk-based patient selection is imperative to improve resource allocation without compromising care. This study aimed to develop predictive models for identifying low-risk patients for transfer to a fully integrated satellite hepatopancreatobiliary (HPB) service in the northeast region of the health-care system.

Novel Common Genetic Susceptibility Loci for Colorectal Cancer.

Background: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk.

Methods: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315).

Quantitative Assessment of Visceral Obesity and Postoperative Colon Cancer Outcomes.

Background: Quantitative computed tomography (CT) assessment of visceral adiposity may be superior to body mass index (BMI) as a predictor of surgical morbidity. We sought to examine the association of CT measures of obesity and BMI with short-term postoperative outcomes in colon cancer patients.

Methods: In this retrospective study, 110 patients treated with colectomy for stage I-III colon cancer were classified as obese or non-obese by preoperative CT-based measures of adiposity or BMI [obese: BMI ≥ 30 kg/m, visceral fat area (VFA) to subcutaneous fat area ratio (V/S) ≥0.

Experiences and expectations of a novel X-ray microsource with focusing mirror. I. erratum.

The following are corrections to a paper by Bloomer & Arndt [(1999), Acta Cryst. D55, 1672-1680]. The entry in the second row of the I(MAR) column of Table 1(b) on page 1674 should read 6.

Experiences and expectations of a novel X-ray microsource with focusing mirror. I.

Data are presented from a novel microfocus X-ray generator installed with a choice of ellipsoidal specularly reflecting mirrors. Diffraction data from proteins show the useful flux from this low-power device to be approaching equivalence with that from many far more powerful generators. Intensity measurements show that for small crystals the brilliance is now restricted by the performance of the mirror, which appears to be limited by imperfections in the figure of its surface rather than by a low reflectivity.

New developments in X-ray optics for macromolecular crystallography using laboratory X-ray sources.

A variety of different devices has been described recently for conditioning the X-ray beam incident on the sample for structural studies on proteins and other macromolecular crystals.

1.9 A structure of the therapeutic antibody CAMPATH-1H fab in complex with a synthetic peptide antigen.

CAMPATH-1 antibodies have a long and successful history in the treatment of leukaemia, autoimmune disease and transplant rejection. The first antibody to undergo "humanisation", CAMPATH-1H, permits treatment with limited patient anti-globulin response. It recognises the CD52 antigen which is a small glycosylphosphatidylinositol(GPI)-anchored protein expressed on lymphocytes and mediates cell depletion.

Crystal structures of a rat anti-CD52 (CAMPATH-1) therapeutic antibody Fab fragment and its humanized counterpart.

The CAMPATH-1 family of antibodies are able systematically to lyse human lymphocytes with human complement by targeting the small cell-surface glycoprotein CD52, commonly called the CAMPATH-1 antigen. These antibodies have been used clinically for several years, providing therapy for patients with a variety of immunologically mediated diseases. We report here the first X-ray crystallographic analyses of a Fab fragment from a rat antibody, the original therapeutic monoclonal CAMPATH-1G and its humanized counterpart CAMPATH-1H, into which the six complementarity-determining regions of the rat antibody have been introduced.

Three dimensional structure of human C-reactive protein.

The structure of the classical acute phase reactant human C-reactive protein provides evidence that phosphocholine binding is mediated through calcium and a hydrophobic pocket centred on Phe 66. The residue Glu 81 is suitably positioned to interact with the choline group. A cleft on the pentameric face opposite to that containing the calcium site may have an important functional role.

Direct visualization of the structure of the "20 S" aggregate of coat protein of tobacco mosaic virus. The "disk" is the major structure at pH 7.0 and the Proto-helix at lower pH.

We have employed the rapid-freeze technique to prepare specimens for electron microscopy of a coat protein solution of tobacco mosaic virus at equilibrium at pH 7.0 and 6.8, ionic strength 0.

Correlation of co-ordinated amino acid substitutions with function in viruses related to tobacco mosaic virus.

Sequence data are available for the coat proteins of seven tobamoviruses, with homologies ranging from at least 26% to 82%, and atomic co-ordinates are known for tobacco mosaic virus (TMV) vulgare. A significant spatial relationship has been found between groups of residues with identical amino acid substitution patterns. This strongly suggest that their location is linked to a particular function, at least in viruses identical with the wild-type for these residues.

Oligonucleotide binding to the coat protein disk of tobacco mosaic virus. Possible steps in the mechanism of assembly.

Binding of the oligoribonucleotides AAG, AAGAAG and AAGAAGUUG to the disk aggregate of tobacco mosaic virus coat protein has been studied in solution under conditions favourable for virus assembly. The two longer oligomers bind strongly with Kd around 1 microM, approach complete saturation of binding sites and cause the formation of long, nicked helical rods resembling the virus. It is suggested that the binding of these oligomers, with sequences chosen from the assembly origin of the viral RNA, simulates the tobacco mosaic virus assembly process.

Correlation between segmental mobility and the location of antigenic determinants in proteins.

Most continuous antigenic determinants of tobacco mosaic virus protein (TMVP), myoglobin and lysozyme correspond to those surface regions in the protein structure, as determined by X-ray crystallography, which possess a run of high-temperature factors along the polypeptide backbone, that is, a high segmental mobility. The mobility of an antigenic determinant may make it easier to adjust to a pre-existing antibody site not fashioned to fit the exact geometry of a protein. The correlation found between temperature factors and antigenicity is better than that between hydrophilicity and antigenicity.

On the three-dimensional structure and catalytic mechanism of triose phosphate isomerase.

Triose phosphate isomerase is a dimeric enzyme of molecular mass 56 000 which catalyses the interconversion of dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde-3-phosphate. The crystal structure of the enzyme from chicken muscle has been determined at a resolution of 2.5 A, and an independent determination of the structure of the yeast enzyme has just been completed at 3 A resolution.