Tag: pubmed

Bioinform Adv. 2023 Aug 22;3(1):vbad109. doi: 10.1093/bioadv/vbad109. eCollection 2023.

ABSTRACT

MOTIVATION: Genetic biases in the human antibody repertoire result in publicly available antibody sequence datasets that contain many duplicate or highly similar sequences. Available datasets are further skewed by the predominance of studies focused on specific disease states, primarily cancer, autoimmunity, and a small number of infectious diseases that includes HIV, influenza, and SARS-CoV-2. These biases and redundancies are a barrier to rapid similarity searches and reduce the efficiency with which these datasets can be used to train statistical or machine-learning models. Identity-based clustering provides a solution; however, the extremely large size of available antibody sequence datasets makes such clustering operations computationally intensive and potentially out of reach for many scientists and researchers who would benefit from such data.

RESULTS: Antibody Reference Clusters (AntiRef), which is modeled after UniRef, provides clustered datasets of filtered human antibody sequences. Due to the modular nature of recombined antibody genes, the clustering thresholds used by UniRef for general protein sequences are suboptimal for antibody clustering. Starting with an input dataset of ∼451M full-length, productive human antibody sequences, AntiRef provides reference datasets clustered at a range of antibody-optimized identity thresholds. AntiRef90 is one-third the size of the input dataset and less than half the size of the non-redundant AntiRef100.

AVAILABILITY AND IMPLEMENTATION: AntiRef datasets are available on Zenodo (zenodo.org/record/7474336). All code used to generate AntiRef is available on GitHub (github.com/briney/antiref). The AntiRef versioning scheme (current version: v2022.12.14) refers to the date on which sequences were retrieved from OAS.

PMID:37886711 | PMC:PMC10598580 | DOI:10.1093/bioadv/vbad109

J Pharm Policy Pract. 2023 Oct 27;16(1):128. doi: 10.1186/s40545-023-00638-w.

ABSTRACT

OBJECTIVES: Competencies refer to the knowledge, skills, attitudes, and behaviors individuals develop through education, training, and experience. These competencies can be formulated into a framework to support practitioner development for effective and sustained performance. In the absence of a national framework for pharmacy education and practice in Lebanon, the Order of Pharmacists of Lebanon (OPL, the official association of pharmacists in Lebanon) pioneered the development of a pharmacy competency framework in 2017. This study aimed to validate and assess the specialized competency framework for pharmacists in sales and marketing (SCF-PSM) after updating the framework previously published by the OPL. The secondary objective was to assess, in a pilot survey, the personal characteristics associated with these competencies.

METHODS: After validating the content of the specialized competency framework, a survey involving Lebanese pharmacists was performed through a 15-min online questionnaire distributed over social media platforms, groups of pharmacists, and individual pharmacists’ contact numbers.

KEY FINDINGS: Pharmaceutical knowledge, communication, emergency response, and operation management during emergencies were satisfactory (more than 80/100). Other activities during emergencies, such as patient care and population health interventions and evaluation, research, and dissemination of research outcomes, received a moderate score (75-78/100), similar to legal practice (78/100), teamwork (76/100), and management skills (75/100). The lowest reported confidence was related to professional communication skills (other than communication per se), mainly negotiation, data processing skills, information technology, self-management, and ethical practice (< 75/100). This study reported deficiencies between what is acquired during undergraduate, postgraduate, and continuing education on the one hand and the competency framework suggested by the OPL on the other hand, showing a mismatch between the competencies of working pharmacists acquired during education and the market needs.

CONCLUSIONS: This study validated a competency framework for pharmacists in sales and marketing and explored the current gaps in self-reported competencies. It also identified areas necessitating reinforcement to optimize professional practice and underscored the need for improvement in undergraduate, postgraduate, and continuing professional education.

PMID:37885029 | DOI:10.1186/s40545-023-00638-w

BMC Res Notes. 2023 Oct 26;16(1):295. doi: 10.1186/s13104-023-06568-9.

ABSTRACT

INTRODUCTION: Simultaneous pancreas kidney (SPK) transplantation is an invaluable procedure to enhance the quality of life of insulin-dependent patients with advanced renal disease. The creation of vascular anastomoses of the donor’s pancreas vessels to the recipient’s, is of utmost importance to predict the graft outcome and surgical complications. In the study we introduce a novel technique for arterial reconstruction during SPK transplantation.

METHODS: Conventionally, during the SPK transplantation, a so-called Y-graft is anastomosed between donor’s superior mesenteric and splenic artery to the recipient’s right iliac artery. In the study we adopted a new technique by preparing an extra extension using the donor’s carotid artery, to be anastomosed to the Y-graft and the iliac artery. In this non-blinded randomized clinical trial we compared the surgical complications and early outcomes between the 2 groups of patients with the traditional and new arterial reconstruction techniques during 3 months after transplantation.

RESULTS: Thirty adult patients were included in the study. The incidence of pancreatitis, vascular thrombosis and surgical site infection was lower in the new Y-graft and extension technique, which was not statistically significant. However, the calculated Cohen’s d index showed the medium effect of new Y-graft and extension technique on complication after SPK transplantations.

CONCLUSION: The post-operative complications tend to be lower in the novel arterial reconstruction technique, however a study on a larger patient group is encouraged to confirm our primary results.

TRIAL REGISTRATION: The study was registered at the Iranian Registry of Clinical Trials on 12/05/2022; IRCT 20210625051701N2; ( http://www.irct.ir/ ).

PMID:37885028 | DOI:10.1186/s13104-023-06568-9

Drug Metab Dispos. 2023 Oct 26:DMD-AR-2023-001500. doi: 10.1124/dmd.123.001500. Online ahead of print.

ABSTRACT

Cytochrome P450 family 1 subfamily A member 2 (CYP1A2), performs an indispensable role in metabolism of both exogenous and endogenous substances. What is more, CYP1A2 functions in human diseases by regulating homeostasis of cholesterol. Despite the emergence of gene-editing animal models, genetically humanized animals that overcome species differences for further exploring the role of CYP1A2 in drug metabolism and human diseases have not yet been constructed. In this study, we inserted human CYP1A2 cDNA into the rat Cyp1a2 gene by using CRISPR/Cas9 technology. Results showed that human CYP1A2 was successfully expressed in humanized rat liver and there were no statistically significant differences of physiological symptoms compared with wild-type (WT) rats. In vitro incubation results indicated the different inhibition of furafylline on CYP1A2 activity in human liver microsomes, humanized CYP1A2 (hCYP1A2) rat liver microsomes, and WT rat liver microsomes, with IC₅₀ values of 7.1 μM, 36.5 μM, and 285.8 μM, respectively. Meanwhile, pharmacokinetic characteristics of clozapine were conducted, and the results suggested that in hCYP1A2 rats, clozapine tended to be metabolized into norclozapine. Both the in vitro and in vivo results demonstrated the different metabolic functions of CYP1A2 in humanized and WT rats. We successfully constructed a novel humanized CYP1A2 rat model using the CRISPR/Cas9 system, providing a powerful tool for better predicting CYP1A2-mediated drug metabolism and pharmacokinetics. Significance Statement Human CYP1A2 takes active part both in the biotransformation of exogenous substances and endogenous substances. Meanwhile, it plays a regulatory role in human diseases, including hypercholesterolemia, hypertension as well as various malignant tumors. This study successfully constructed humanized CYP1A2 rat model by CRISPR/Cas9 technology, providing a powerful model for promoting drug development and safety evaluation, as well as further exploring the role of CYP1A2 in human diseases.

PMID:37884392 | DOI:10.1124/dmd.123.001500

Int J Spine Surg. 2023 Oct 26:8551. doi: 10.14444/8551. Online ahead of print.

ABSTRACT

BACKGROUND: Posterior cervical decompression with or without fusion (PCD/F) is used to manage degenerative spinal conditions. Malnutrition has been implicated for poor outcomes in spine surgery. The aim of this study was to assess the ability of the Geriatric Nutritional Risk Index (GNRI) as a risk calculator for postoperative complications in patients undergoing PCD/F.

METHODS: The 2006 to 2018 American College of Surgeons National Surgery Quality Improvement Program Database was queried for patients undergoing PCD/F. Nutritional status was categorized as normal (GNRI greater than 98), moderately malnourished (GNRI 92-98), or severely malnourished (GNRI less than or equal to 92). Complications within 30 days of surgery were compared among the groups. Preoperative data that were statistically significant (P < 0.05) upon univariate χ² analysis were included in the univariate then multivariate binary regression model to calculate adjusted ORs. All ORs were assessed at the 95% CI.

RESULTS: Of the 7597 PCD/F patients identified, 15.6% were severely malnourished and 19.1% were moderately malnourished. Severe and moderate malnourishment were independent risk factors for mortality (OR = 3.790, 95% CI 2.492-5.763, P < 0.001; OR = 2.150, 95% CI 1.351-3.421, P = 0.011). Severe malnourishment was an independent risk factor for sepsis/septic shock (OR = 3.448, 95% CI 2.402-4.948, P < 0.001).

CONCLUSIONS: In elderly patients undergoing PCD/F, severe malnutrition, as defined by the GNRI, was an independent risk factor for mortality and sepsis/septic shock.

CLINICAL RELEVANCE: The GNRI may be more useful than other indices for risk stratification in elderly patients because it accounts for confounding variables such as hydration status and paradoxical malnourishment in obese patients.

PMID:37884336 | DOI:10.14444/8551

J Orthop Res. 2023 Oct 26. doi: 10.1002/jor.25720. Online ahead of print.

ABSTRACT

Rifampin has been proven to be effective in the treatment of prosthetic infections due to its ability to intercalate into biofilms. The use of rifampin in antibiotic spacers is not well described, which would be especially important in the local periprosthetic environment where parenteral doses have poor penetration. Null hypothesis tests if rifampin use in PMMA cement will show no clinically significant impact on mechanical strength at antibiotic concentrations that remain bactericidal. Test antibiotic cement samples supplemented with 0mg, 30mg, 50mg, 100mg, 150mg or 200mg of rifampin into a standard 40g bag were tested for compression to failure using published ASTM standards. The samples were then inoculated with Pseudomonas aeruginosa and either evaluated for lipo-polysacharide (LPS) presence as a marker of biofilm or tested by elution as the Kirby Bauer assay. Rifampin concentrations of 30mg, and 50mg, showed no statistically different mechanical characteristics to control PMMA (p>0.05). The 100mg sample fell within the acceptable range of compressive strength and had significantly less LPS and bacterial presence compared to control at 12 and 24 hours. The ability of PMMA with 100mg of rifampin to maintain its structural integrity and have significant bacterial inhibition at 12 and 24 hours makes it a great candidate as an antibiotic bone cement additive. PMMA loaded with up to 100mg of rifampin shows promise in the treatment and prevention of PJI for total knee and total hip arthroplasty. This article is protected by copyright. All rights reserved.

PMID:37884321 | DOI:10.1002/jor.25720

Prev Chronic Dis. 2023 Oct 26;20:E94. doi: 10.5888/pcd20.230071.

ABSTRACT

INTRODUCTION: We examined national estimates of breast, cervical, and colorectal cancer (CRC) screening test use and compared them with Healthy People 2030 national targets. Test use in 2021 was compared with prepandemic estimates.

METHODS: In 2022, we used 2021 National Health Interview Survey (NHIS) data to estimate proportions of adults up to date with US Preventive Services Task Force recommendations for breast (women aged 50-74 y), cervical (women aged 21-65 y), and CRC screening (adults aged 50-75 y) across sociodemographic and health care access variables. We compared age-standardized estimates from the 2021 and 2019 NHIS.

RESULTS: Percentages of adults up to date in 2021 were 75.7% (95% CI, 74.4%-76.9%), 75.2% (95% CI, 73.9%-76.4%), and 72.2% (95% CI, 71.2%-73.2%) for breast, cervical, and CRC screening, respectively. Estimates were below 50% among those without a wellness check in 3 years (all screening types), among those without a usual source of care or insurance (aged <65 y) (breast and CRC screening), and among those residing in the US for less than 10 years (CRC screening). Percentages of adults who were up to date with breast and cervical cancer screening and colonoscopy were similar in 2019 and 2021. Fecal occult blood/fecal immunochemical test (FOBT/FIT) use was modestly higher in 2021 (P < .001).

CONCLUSIONS: In 2021, approximately 1 in 4 adults of screening age were not up to date with breast, cervical, and CRC screening recommendations, and Healthy People 2030 national targets were not met. Disparities existed across several characteristics, particularly those related to health care access. Breast, cervical, and colonoscopy test use within recommended screening intervals approximated prepandemic levels. FOBT/FIT estimates were modestly higher in 2021.

PMID:37884318 | DOI:10.5888/pcd20.230071

AJNR Am J Neuroradiol. 2023 Oct 26. doi: 10.3174/ajnr.A8026. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: The human auditory system develops early in fetal life. This retrospective MR imaging study describes the in vivo prenatal anatomic development of the transverse temporal gyrus (Heschl gyrus) site of the primary auditory cortex.

MATERIALS AND METHODS: Two hundred seventy-two MR imaging studies of the fetal brain (19-39 weeks’ gestational age) acquired from a single institution’s 1.5T scanner were retrospectively examined by 2 neuroradiologists. MR imaging with pathologic findings and extreme motion artifacts was excluded. Postnatal Heschl gyrus landmarks were used as a reference on T2-weighted ssFSE sequences in the 3 orthogonal planes. The frequency of the Heschl gyrus was reported for gestational age, hemisphere, and planes. Descriptive statistics and a McNemar test were performed.

RESULTS: Two hundred thirty MR imaging studies were finally included. Fetal brains were divided by gestational age (in weeks) into 8 groups (parentheses indicate the number of observations): 19-21 (29), 22-23 (32), 24-25 (21), 26-27 (18), 28-29 (35), 30-31 (30), 32-33 (33) and >34 (32). The Heschl gyrus appeared on MR imaging between 24 and 25 weeks’ gestational age (14/21 fetuses, 67%) and was visible in all fetuses after the 28th week of gestation. By its appearance (24-28 weeks’ gestational age), the sagittal plane was the most sensitive in its detectability. After 28-29 weeks’ gestational age, the Heschl gyrus was evident in all acquisition planes and fetuses. Results did not differ between hemispheres.

CONCLUSIONS: The Heschl gyrus appears on MR imaging at 24-25 weeks’ gestational age, paralleling the functional activation of the auditory system. We propose the Heschl gyrus as an early additional MR imaging marker of fetal brain development.

PMID:37884303 | DOI:10.3174/ajnr.A8026

AJNR Am J Neuroradiol. 2023 Oct 26. doi: 10.3174/ajnr.A8032. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: The radiologic prevalence of superior semicircular canal dehiscence in the asymptomatic population has been widely studied, but less is known about the rates of other forms of third window dehiscence. Per the existing literature, the radiologic prevalence of cochlear-facial nerve dehiscence, for example, exceeds that seen in histologic studies, suggesting that conventional CT is unreliable for cochlear-facial dehiscence. These studies relied on nonisometric CT acquisitions, however, and underused multiplanar reformatting techniques, leading to false-positive findings. Our purpose was to determine the rate of cochlear-facial dehiscence and other non-superior semicircular canal third window dehiscences on optimized CT in asymptomatic patients.

MATERIALS AND METHODS: Sixty-four-channel temporal bone CT scans from 602 patients in emergency departments were assessed for cochlear-facial and other non-superior semicircular canal third window dehiscences by using high-resolution, multiplanar oblique reformats. Confidence intervals for dehiscence prevalence were calculated using the Newcombe 95% interval confidence method.

RESULTS: Of 602 patients, 500 were asymptomatic, while 102 had an imaging indication consistent with possible third window syndrome (symptomatic). Eight asymptomatic patients (1.6%) had cochlear-facial dehiscence, while 43 (8.4%) had jugular bulb-vestibular aqueduct dehiscence. There was no statistically significant difference between the prevalence of cochlear-facial dehiscence or jugular bulb-vestibular aqueduct dehiscence in asymptomatic patients compared with symptomatic patients. Cochlear-carotid canal, cochlear-internal auditory canal, and cochlear-petrosal sinus dehiscences were not observed.

CONCLUSIONS: Sixty-four-channel CT with multioblique reformatting is sensitive and specific for identifying cochlear-facial dehiscence, with rates similar to those in postmortem series. Jugular bulb-vestibular aqueduct dehiscence is a common incidental finding and is unlikely to produce third window physiology. Other non-superior semicircular canal third window dehiscences are rare in asymptomatic patients.

PMID:37884302 | DOI:10.3174/ajnr.A8032

AJNR Am J Neuroradiol. 2023 Oct 26. doi: 10.3174/ajnr.A8034. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: IDH-mutant gliomas are further divided on the basis of 1p/19q status: oligodendroglioma, IDH-mutant and 1p/19q-codeleted, and astrocytoma, IDH-mutant (without codeletion). Occasionally, testing may reveal single-arm 1p or 19q deletion (unideletion), which remains within the diagnosis of astrocytoma. Molecular assessment has some limitations, however, raising the possibility that some unideleted tumors could actually be codeleted. This study assessed whether unideleted tumors had MR imaging features and survival more consistent with astrocytomas or oligodendrogliomas.

MATERIALS AND METHODS: One hundred twenty-one IDH-mutant grade 2-3 gliomas with 1p/19q results were identified. Two neuroradiologists assessed the T2-FLAIR mismatch sign and calcifications, as differentiators of astrocytomas and oligodendrogliomas. MR imaging features and survival were compared among the unideleted tumors, codeleted tumors, and those without 1p or 19q deletion.

RESULTS: The cohort comprised 65 tumors without 1p or 19q deletion, 12 unideleted tumors, and 44 codeleted. The proportion of unideleted tumors demonstrating the T2-FLAIR mismatch sign (33%) was similar to that in tumors without deletion (49%; P = .39), but significantly higher than codeleted tumors (0%; P = .001). Calcifications were less frequent in unideleted tumors (0%) than in codeleted tumors (25%), but this difference did not reach statistical significance (P = .097). The median survival of patients with unideleted tumors was 7.8 years, which was similar to that in tumors without deletion (8.5 years; P = .72) but significantly shorter than that in codeleted tumors (not reaching median survival after 12 years; P = .013).

CONCLUSIONS: IDH-mutant gliomas with single-arm 1p or 19q deletion have MR imaging appearance and survival that are similar to those of astrocytomas without 1p or 19q deletion and significantly different from those of 1p/19q-codeleted oligodendrogliomas.

PMID:37884300 | DOI:10.3174/ajnr.A8034