The journey to building a diverse, equitable, and inclusive American Medical Informatics Association.

OBJECTIVE: The American Medical Informatics Association (AMIA) Task Force on Diversity, Equity, and Inclusion (DEI) was established to address systemic racism and health disparities in biomedical and health informatics, aligning with AMIA's mission to transform healthcare. AMIA's DEI initiatives were spurred by member voices responding to police brutality and COVID-19's impact on Black/African American communities. MATERIALS AND METHODS: The Task Force, consisting of 20 members across 3 groups aligned with AMIA's 2020-2025 Strategic Plan, met biweekly to develop DEI recommendations with the help of 16 additional volunteers. These recommendations were reviewed, prioritized, and presented to the AMIA Board of Directors for approval. RESULTS: In 9 months, the Task Force (1) created a logic model to support workforce diversity and raise AMIA's DEI awareness, (2) conducted an environmental scan of other associations' DEI activities, (3) developed a DEI framework for AMIA meetings, (4) gathered member feedback, (5) cultivated DEI educational resources, (6) created a Board nominations and diversity session, (7) reviewed the Board's Strategic Planning for DEI alignment, (8) led a program to increase diversity at the 2020 AMIA Virtual Annual Symposium, and (9) standardized socially-assigned race and ethnicity data collection. DISCUSSION: The Task Force proposed actionable recommendations that focused on AMIA's role in addressing systemic racism and health equity, helping the organization understand its member diversity. CONCLUSION: This work supported marginalized groups, broadened the research agenda, and positioned AMIA as a DEI leader while reinforcing the need for ongoing transformation within informatics.

Scalable incident detection via natural language processing and probabilistic language models.

Post marketing safety surveillance depends in part on the ability to detect concerning clinical events at scale. Spontaneous reporting might be an effective component of safety surveillance, but it requires awareness and understanding among healthcare professionals to achieve its potential. Reliance on readily available structured data such as diagnostic codes risks under-coding and imprecision. Clinical textual data might bridge these gaps, and natural language processing (NLP) has been shown to aid in scalable phenotyping across healthcare records in multiple clinical domains. In this study, we developed and validated a novel incident phenotyping approach using unstructured clinical textual data agnostic to Electronic Health Record (EHR) and note type. It's based on a published, validated approach (PheRe) used to ascertain social determinants of health and suicidality across entire healthcare records. To demonstrate generalizability, we validated this approach on two separate phenotypes that share common challenges with respect to accurate ascertainment: (1) suicide attempt; (2) sleep-related behaviors. With samples of 89,428 records and 35,863 records for suicide attempt and sleep-related behaviors, respectively, we conducted silver standard (diagnostic coding) and gold standard (manual chart review) validation. We showed Area Under the Precision-Recall Curve of ~ 0.77 (95% CI 0.75-0.78) for suicide attempt and AUPR ~ 0.31 (95% CI 0.28-0.34) for sleep-related behaviors. We also evaluated performance by coded race and demonstrated differences in performance by race differed across phenotypes. Scalable phenotyping models, like most healthcare AI, require algorithmovigilance and debiasing prior to implementation.

Accelerated 2D radial Look-Locker T1 mapping using a deep learning-based rapid inversion recovery sampling technique.

Efficient abdominal coverage with T1-mapping methods currently available in the clinic is limited by the breath hold period (BHP) and the time needed for T1 recovery. This work develops a T1-mapping framework for efficient abdominal coverage based on rapid T1 recovery curve (T1RC) sampling, slice-selective inversion, optimized slice interleaving, and a convolutional neural network (CNN)-based T1 estimation. The effect of reducing the T1RC sampling was evaluated by comparing T1 estimates from T1RC ranging from 0.63 to 2.0 s with reference T1 values obtained from T1RC = 2.5-5 s. Slice interleaving methodologies were evaluated by comparing the T1 variation in abdominal organs across slices. The repeatability of the proposed framework was demonstrated by performing acquisition on test subjects across imaging sessions. Analysis of in vivo data based on retrospectively shortening the T1RC showed that with the CNN framework, a T1RC = 0.84 s yielded T1 estimates without significant changes in mean T1 (p > 0.05) or significant increase in T1 variability (p > 0.48) compared to the reference. Prospectively acquired data using T1RC = 0.84 s, an optimized slice interleaving scheme, and the CNN framework enabled 21 slices in a 20 s BHP. Analyses across abdominal organs produced T1 values within 2% of the reference. Repeatability experiments yielded Pearson's correlation, repeatability coefficient, and coefficient of variation of 0.99, 2.5%, and 0.12%, respectively. The proposed T1 mapping framework provides full abdominal coverage within a single BHP.

Mapping extrachromosomal DNA amplifications during cancer progression.

To understand the role of extrachromosomal DNA (ecDNA) amplifications in cancer progression, we detected and classified focal amplifications in 8,060 newly diagnosed primary cancers, untreated metastases and heavily pretreated tumors. The ecDNAs were detected at significantly higher frequency in untreated metastatic and pretreated tumors compared to newly diagnosed cancers. Tumors from chemotherapy-pretreated patients showed significantly higher ecDNA frequency compared to untreated cancers. In particular, tubulin inhibition associated with ecDNA increases, suggesting a role for ecDNA in treatment response. In longitudinally matched tumor samples, ecDNAs were more likely to be retained compared to chromosomal amplifications. EcDNAs shared between time points, and ecDNAs in advanced cancers were more likely to harbor localized hypermutation events compared to private ecDNAs and ecDNAs in newly diagnosed tumors. Relatively high variant allele fractions of ecDNA localized hypermutations implicated early ecDNA mutagenesis. Our findings nominate ecDNAs to provide tumors with competitive advantages during cancer progression and metastasis.

Population genomics of seal lice provides insights into the postglacial history of northern European seals.

Genetic analyses of host-specific parasites can elucidate the evolutionary histories and biological features of their hosts. Here, we used population-genomic analyses of ectoparasitic seal lice (Echinophthirius horridus) to shed light on the postglacial history of seals in the Arctic Ocean and the Baltic Sea region. One key question was the enigmatic origin of relict landlocked ringed seal populations in lakes Saimaa and Ladoga in northern Europe. We found that that lice of four postglacially diverged subspecies of the ringed seal (Pusa hispida) and Baltic gray seal (Halichoerus grypus), like their hosts, form genetically differentiated entities. Using coalescent-based demographic inference, we show that the sequence of divergences of the louse populations is consistent with the geological history of lake formation. In addition, local effective population sizes of the lice are generally proportional to the census sizes of their respective seal host populations. Genome-based reconstructions of long-term effective population sizes revealed clear differences among louse populations associated with gray versus ringed seals, with apparent links to Pleistocene and Holocene climatic variation as well as to the isolation histories of ringed seal subspecies. Interestingly, our analyses also revealed ancient gene flow between the lice of Baltic gray and ringed seals, suggesting that the distributions of Baltic seals overlapped to a greater extent in the past than is the case today. Taken together, our results demonstrate how genomic information from specialized parasites with higher mutation and substitution rates than their hosts can potentially illuminate finer scale population genetic patterns than similar data from their hosts.

Defining Documentation Burden (DocBurden) and Excessive DocBurden for All Health Professionals: A Scoping Review.

OBJECTIVES: Efforts to reduce documentation burden (DocBurden) for all health professionals (HP) are aligned with national initiatives to improve clinician wellness and patient safety. Yet DocBurden has not been precisely defined, limiting national conversations and rigorous, reproducible, and meaningful measures. Increasing attention to DocBurden motivated this work to establish a standard definition of DocBurden, with the emergence of excessive DocBurden as a term. METHODS: We conducted a scoping review of DocBurden definitions and descriptions, searching six databases for scholarly, peer-reviewed, and gray literature sources, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extensions for Scoping Review guidance. For the concept clarification phase of work, we used the American Nursing Informatics Association's Six Domains of Burden Framework. RESULTS: A total of 153 articles were included based on a priori criteria. Most articles described a focus on DocBurden, but only 18% (n = 28) provided a definition. We define excessive DocBurden as the stress and unnecessarily heavy work an HP or health care team experiences when usability of documentation systems and documentation activities (i.e., generation, review, analysis, and synthesis of patient data) are not aligned in support of care delivery. A negative connotation was attached to burden without a neutral state in included sources, which does not align with dictionary definitions of burden. CONCLUSION: Existing literature does not distinguish between a baseline or required task load to conduct patient care resulting from usability issues (DocBurden), and the unnecessarily heavy tasks and requirements that contribute to excessive DocBurden. Our definition of excessive DocBurden explicitly acknowledges this distinction, to support development of meaningful measures for understanding and intervening on excessive DocBurden locally, nationally, and internationally.

CSF dynamics throughout the ventricular system using 4D flow MRI: associations to arterial pulsatility, ventricular volumes, and age.

BACKGROUND: Cerebrospinal fluid (CSF) dynamics are increasingly studied in aging and neurological disorders. Models of CSF-mediated waste clearance suggest that altered CSF dynamics could play a role in the accumulation of toxic waste in the CNS, with implications for Alzheimer's disease and other proteinopathies. Therefore, approaches that enable quantitative and volumetric assessment of CSF flow velocities could be of value. In this study we demonstrate the feasibility of 4D flow MRI for simultaneous assessment of CSF dynamics throughout the ventricular system, and evaluate associations to arterial pulsatility, ventricular volumes, and age. METHODS: In a cognitively unimpaired cohort (N = 43; age 41-83 years), cardiac-resolved 4D flow MRI CSF velocities were obtained in the lateral ventricles (LV), foramens of Monro, third and fourth ventricles (V3 and V4), the cerebral aqueduct (CA) and the spinal canal (SC), using a velocity encoding (venc) of 5 cm/s. Cerebral blood flow pulsatility was also assessed with 4D flow (venc = 80 cm/s), and CSF volumes were obtained from T1- and T2-weighted MRI. Multiple linear regression was used to assess effects of age, ventricular volumes, and arterial pulsatility on CSF velocities. RESULTS: Cardiac-driven CSF dynamics were observed in all CSF spaces, with region-averaged velocity range and root-mean-square (RMS) velocity encompassing from very low in the LVs (RMS 0.25 ± 0.08; range 0.85 ± 0.28 mm/s) to relatively high in the CA (RMS 6.29 ± 2.87; range 18.6 ± 15.2 mm/s). In the regression models, CSF velocity was significantly related to age in 5/6 regions, to CSF space volume in 2/3 regions, and to arterial pulsatility in 3/6 regions. Group-averaged waveforms indicated distinct CSF flow propagation delays throughout CSF spaces, particularly between the SC and LVs. CONCLUSIONS: Our findings show that 4D flow MRI enables assessment of CSF dynamics throughout the ventricular system, and captures independent effects of age, CSF space morphology, and arterial pulsatility on CSF motion.

Impact of valve-sparing aortic root replacement on aortic fluid dynamics and biomechanics in patients with syndromic heritable thoracic aortic disease.

OBJECTIVES: Patients with syndromic heritable thoracic aortic diseases (sHTAD) who underwent prophylactic aortic root replacement are at high risk of distal aortic events, but the underlying mechanisms are poorly understood. This prospective, longitudinal study aims to assess the impact of valve-sparing aortic root replacement (VSARR) on aortic fluid dynamics and biomechanics in these patients, and to examine whether they present altered haemodynamics or biomechanics prior to surgery compared to sHTAD patients with no indication for surgery (sHTAD-NSx) and healthy volunteers (HV). METHODS: Sixteen patients with Marfan or Loeys-Dietz syndrome underwent two 4D flow CMR studies before (sHTAD-preSx) and after VSARR (sHTAD-postSx). Two age, sex and BSA matched cohorts of 40 HV and 16 sHTAD-NSx patients with available 4D flow CMR, were selected for comparison. In-plane rotational flow (IRF), systolic flow reversal ratio (SFRR), wall shear stress (WSS), pulse wave velocity (PWV) and aortic strain were analysed in the ascending (AscAo) and descending aorta (DescAo). RESULTS: All patients with sHTAD presented altered haemodynamics and increased aortic stiffness (p<0.05) compared to HV, both in the AscAo (median PWV 7.4 in sHTAD-NSx; 6.8 in sHTAD-preSx; 4.9m/s in HV) and DescAo (median PWV 9.1 in sHTAD-NSx; 8.1 in sHTAD-preSx; 6.3m/s in HV). Patients awaiting VSARR had markedly reduced in-plane (median IRF -2.2 vs 10.4 cm2/s in HV, p=0.001), but increased through-plane flow rotation (median SFRR 7.8 vs 3.8% in HV, p=0.002), and decreased WSS (0.36 vs 0.47N/m2 in HV, p=0.004) in the proximal DescAo. After VSARR, proximal DescAo in-plane rotational flow (p=0.010) and circumferential WSS increased (p=0.011), no longer differing from HV, but through-plane rotational flow, axial WSS and stiffness remained altered. Patients in which aortic tortuosity was reduced after surgery showed greater post-surgical increase in IRF compared to those in which tortuosity increased (median IRF increase 18.1 vs 3.3cm²/s, p=0.047). Most AscAo flow alterations were restored to physiological values after VSARR. CONCLUSIONS: In patients with sHTAD, VSARR partially restores downstream fluid dynamics to physiological levels. However, some flow disturbances and increased stiffness persist in the proximal DescAo. Further longitudinal studies are needed to evaluate whether persistent alterations contribute to post-surgical risk.

Transcriptomic responses to shifts in light and nitrogen in two congeneric diatom species.

Light and nitrogen availability are basic requirements for photosynthesis. Changing in light intensity and nitrogen concentration may require adaptive physiological and life process changes in phytoplankton cells. Our previous study demonstrated that two Thalassiosira species exhibited, respectively, distinctive physiological responses to light and nitrogen stresses. Transcriptomic analyses were employed to investigate the mechanisms behind the different physiological responses observed in two diatom species of the genus Thalassiosira. The results indicate that the congeneric species are different in their cellular responses to the same shifting light and nitrogen conditions. When conditions changed to high light with low nitrate (HLLN), the large-celled T. punctigera was photodamaged. Thus, the photosynthesis pathway and carbon fixation related genes were significantly down-regulated. In contrast, the small-celled T. pseudonana sacrificed cellular processes, especially amino acid metabolisms, to overcome the photodamage. When changing to high light with high nitrate (HLHN) conditions, the additional nitrogen appeared to compensate for the photodamage in the large-celled T. punctigera, with the tricarboxylic acid cycle (TCA cycle) and carbon fixation significantly boosted. Consequently, the growth rate of T. punctigera increased, which suggest that the larger-celled species is adapted for forming post-storm algal blooms. The impact of high light stress on the small-celled T. pseudonana was not mitigated by elevated nitrate levels, and photodamage persisted.

Enhancing Postmarketing Surveillance of Medical Products With Large Language Models.

Importance: The Sentinel System is a key component of the US Food and Drug Administration (FDA) postmarketing safety surveillance commitment and uses clinical health care data to conduct analyses to inform drug labeling and safety communications, FDA advisory committee meetings, and other regulatory decisions. However, observational data are frequently deemed insufficient for reliable evaluation of safety concerns owing to limitations in underlying data or methodology. Advances in large language models (LLMs) provide new opportunities to address some of these limitations. However, careful consideration is necessary for how and where LLMs can be effectively deployed for these purposes. Observations: LLMs may provide new avenues to support signal-identification activities to identify novel adverse event signals from narrative text of electronic health records. These algorithms may be used to support epidemiologic investigations examining the causal relationship between exposure to a medical product and an adverse event through development of probabilistic phenotyping of health outcomes of interest and extraction of information related to important confounding factors. LLMs may perform like traditional natural language processing tools by annotating text with controlled vocabularies with additional tailored training activities. LLMs offer opportunities for enhancing information extraction from adverse event reports, medical literature, and other biomedical knowledge sources. There are several challenges that must be considered when leveraging LLMs for postmarket surveillance. Prompt engineering is needed to ensure that LLM-extracted associations are accurate and specific. LLMs require extensive infrastructure to use, which many health care systems lack, and this can impact diversity, equity, and inclusion, and result in obscuring significant adverse event patterns in some populations. LLMs are known to generate nonfactual statements, which could lead to false positive signals and downstream evaluation activities by the FDA and other entities, incurring substantial cost. Conclusions and Relevance: LLMs represent a novel paradigm that may facilitate generation of information to support medical product postmarket surveillance activities that have not been possible. However, additional work is required to ensure LLMs can be used in a fair and equitable manner, minimize false positive findings, and support the necessary rigor of signal detection needed for regulatory activities.

Evaluation of the effectiveness of a video-based educational intervention on perinatal mental health related stigma reduction strategies for healthcare professionals: A single group pre-test-post-test pilot study.

BACKGROUND: Healthcare professionals have a role to play in reducing perinatal mental health related stigma. AIM: To assess the effectiveness of a video-based educational intervention developed to provide guidance to healthcare professionals on perinatal mental health related stigma reduction strategies. DESIGN: A single group pre-test-post-test pilot study with no control group. SETTING(S): A university affiliated maternity hospital in Ireland PARTICIPANTS: A convenience sample of registered midwives, nurses and doctors (n = 60) recruited from October 2020-January 2021. INTERVENTION: A twenty-minute video-based educational intervention. METHODS: Respondents (n = 60) completed a pre-test (time point one) and post-test (time point-two) questionnaire, and a three-month follow-up post-test questionnaire (time point-three) (n = 39). The questionnaire included the Mental Illness Clinicians' Attitudes Scale, Reported and Intended Behaviour Scale, Reynolds Empathy Scale and open-ended questions. Wilcoxon Signed Rank Test was selected to evaluate the pre-test post-test scores. RESULTS: The difference in mean Mental Illness: Clinicians' Attitudes-4 scores were statistically significant between time points one and three (z = 3.27, df=36, P = 0.0007) suggesting more positive attitudes towards people with mental health conditions after the intervention. The mean total score for the Reported and Intended Behaviour Scale increased from 18.7 (SD 1.87) at time point one to 19.2 (SD 1.60) at time point two (z= -3.368, df=59, P = 0.0004) suggesting an increase in positive intended behaviours towards those with mental health issues immediately following the intervention. These findings were also corroborated by responses to open-ended survey questions. CONCLUSIONS: Further research with a larger sample of healthcare professionals evaluated over a longer period would provide further evidence for the sustainability of the intervention. TWEETABLEABSTRACT: A video-based intervention can increase healthcare professionals' knowledge of perinatal #mentalhealth related stigma reduction strategies @Journal. Link to article.

Biogeographic history of pigeons and doves drives the origin and diversification of their parasitic body lice.

Despite their extensive diversity and ecological importance, the history of diversification for most groups of parasitic organisms remains relatively understudied. Elucidating broad macroevolutionary patterns of parasites is challenging, often limited by the availability of samples, genetic resources, and knowledge about ecological relationships with their hosts. In this study, we explore the macroevolutionary history of parasites by focusing on parasitic body lice from doves. Building on extensive knowledge of ecological relationships and previous phylogenomic studies of their avian hosts, we tested specific questions about the evolutionary origins of the body lice of doves, leveraging whole genome data sets for phylogenomics. Specifically, we sequenced whole genomes from 68 samples of dove body lice, including representatives of all body louse genera from 51 host taxa. From these data, we assembled >2,300 nuclear genes to estimate dated phylogenetic relationships among body lice and several outgroup taxa. The resulting phylogeny of body lice was well supported, although some branches had conflicting signal across the genome. We then reconstructed ancestral biogeographic ranges of body lice and compared the body louse phylogeny to phylogeny of doves, and also to a previously published phylogeny of the wing lice of doves. Divergence estimates placed the origin of body lice in the late Oligocene. Body lice likely originated in Australasia and dispersed with their hosts during the early Miocene, with subsequent codivergence and host switching throughout the world. Notably, this evolutionary history is very similar to that of dove wing lice, despite the stronger dispersal capabilities of wing lice compared to body lice. Our results highlight the central role of the biogeographic history of host organisms in driving the evolutionary history of their parasites across time and geographic space.

Biotransformation research advances - 2023 year in review.

This annual review marks the eighth in the series starting with Baillie et al. (2016) Our objective is to explore and share articles which we deem influential and significant in the field of biotransformation. Its format is to highlight important aspects captured in synopsis followed by a commentary with relevant figure and references.

On Demand Bioorthogonal Switching of an Antibody-Conjugated SPECT Probe to a Cytotoxic Payload: from Imaging to Therapy.

Antibody-drug conjugates (ADCs) for the treatment of cancer aim to achieve selective delivery of a cytotoxic payload to tumor cells while sparing normal tissue. In vivo, multiple tumor-dependent and -independent processes act on ADCs and their released payloads to impact tumor-versus-normal delivery, often resulting in a poor therapeutic window. An ADC with a labeled payload would make synchronous correlations between distribution and tissue-specific pharmacological effects possible, empowering preclinical and clinical efforts to improve tumor-selective delivery; however, few methods to label small molecules without destroying their pharmacological activity exist. Herein, we present a bioorthogonal switch approach that allows a radiolabel attached to an ADC payload to be removed tracelessly at will. We exemplify this approach with a potent DNA-damaging agent, the pyrrolobenzodiazepine (PBD) dimer, delivered as an antibody conjugate targeted to lung tumor cells. The radiometal chelating group, DOTA, was attached via a novel trans-cyclooctene (TCO)-caged self-immolative para-aminobenzyl (PAB) linker to the PBD, stably attenuating payload activity and allowing tracking of biodistribution in tumor-bearing mice via SPECT-CT imaging (live) or gamma counting (post-mortem). Following TCO-PAB-DOTA reaction with tetrazines optimized for extra- and intracellular reactivity, the label was removed to reveal the unmodified PBD dimer capable of inducing potent tumor cell killing in vitro and in mouse xenografts. The switchable antibody radio-drug conjugate (ArDC) we describe integrates, but decouples, the two functions of a theranostic given that it can serve as a diagnostic for payload delivery in the labeled state, but can be switched on demand to a therapeutic agent (an ADC).

Bioactivation and reactivity research advances - 2023 year in review.

Advances in the field of bioactivation have significantly contributed to our understanding and prediction of drug-induced liver injury (DILI). It has been established that many adverse drug reactions, including DILI, are associated with the formation and reactivity of metabolites. Modern methods allow us to detect and characterize these reactive metabolites in earlier stages of drug development, which helps anticipate and circumvent the potential for DILI. Improved in silico models and experimental techniques that better reflect in vivo environments are enhancing predictive capabilities for DILI risk. Further, studies on the mechanisms of bioactivation, including enzyme interactions and the role of individual genetic differences, have provided valuable insights for drug optimizations. Cumulatively, this progress is continually refining our approaches to drug safety evaluation and personalized medicine.

Rate of oophorectomy in pediatric ovarian torsion: risk factors and change over time.

PURPOSE: The management of ovarian torsion in pediatric patients has evolved over time. Ovarian salvage is currently recommended given concerns for fertility preservation and the low likelihood of malignancy. Studies have shown that the incidence of oophorectomy is higher amongst pediatric surgeons in comparison to gynecologists. Using a national database, this study examined how the surgical management of ovarian torsion has evolved. METHODS: Children with a discharge diagnosis of ovarian torsion (ICD-9 code 620.5, ICD-10 code N835X) and procedure codes for oophorectomy (CCS code 119) were identified within the KID database from 2003, 2006, 2009, 2012, 2016, and 2019. Diagnosis of ovarian pathology was based upon ICD-9 and ICD-10 codes at the time of discharge. RESULTS: A total of 7008 patients, ages 1-20, had a discharge diagnosis of ovarian torsion. Of those patients, 2,597 (37.1%) were diagnosed with an ovarian cyst, 1560 (22.2%) were diagnosed with a benign ovarian neoplasm, and 30 (0.4%) were diagnosed with a malignant neoplasm. There was a decreased risk of oophorectomy in urban-teaching versus rural hospitals (OR: 0.64, p < 0.001). The rate of oophorectomy has decreased overtime. However, patients with benign or malignant neoplasms were more likely to undergo oophorectomy than those without a diagnosis (OR: 2.03, p < 0.001; 4.82, p < 0.001). CONCLUSION: The rate of oophorectomy amongst children with ovarian torsion has decreased over time. Yet, despite improvements, oophorectomy is common amongst patients with benign ovarian neoplasms and those treated at rural hospitals. Continued education is needed to optimize patient care in all clinical scenarios. LEVEL OF EVIDENCE: IV.

Metabolism of new drug modalities research advances - 2023 year in review.

With contributions from colleagues across academia and industry, we have put together the annual reviews of research advances on drug biotransformation and bioactivation since 2016 led by Cyrus Khojasteh. While traditional small molecules and biologics are still predominant in drug discovery, we start to notice a paradigm shift toward new drug modalities (NDMs) including but not limited to peptide and oligonucleotide therapeutics, protein degraders (heterobifunctional degraders and molecule glues), conjugated drugs and covalent inhibitors. The readers can learn more on each new drug modality from several recent comprehensive reviews (Blanco et al. 2022; Hillebrand et al. 2024; Phuna et al. 2024). Based on this trend, we put together this stand-alone review branched from our previous efforts (Baillie et al. 2016; Khojasteh et al. 2023) with a focus on the metabolism of NDMs. We collected 11 articles which exemplify recent discoveries and perspectives in this field.

Rapid Targeted Assembly of the Proteome Reveals Evolutionary Variation of GC Content in Avian Lice.

Nucleotide base composition plays an influential role in the molecular mechanisms involved in gene function, phenotype, and amino acid composition. GC content (proportion of guanine and cytosine in DNA sequences) shows a high level of variation within and among species. Many studies measure GC content in a small number of genes, which may not be representative of genome-wide GC variation. One challenge when assembling extensive genomic data sets for these studies is the significant amount of resources (monetary and computational) associated with data processing, and many bioinformatic tools have not been optimized for resource efficiency. Using a high-performance computing (HPC) cluster, we manipulated resources provided to the targeted gene assembly program, automated target restricted assembly method (aTRAM), to determine an optimum way to run the program to maximize resource use. Using our optimum assembly approach, we assembled and measured GC content of all of the protein-coding genes of a diverse group of parasitic feather lice. Of the 499 426 genes assembled across 57 species, feather lice were GC-poor (mean GC = 42.96%) with a significant amount of variation within and between species (GC range = 19.57%-73.33%). We found a significant correlation between GC content and standard deviation per taxon for overall GC and GC3, which could indicate selection for G and C nucleotides in some species. Phylogenetic signal of GC content was detected in both GC and GC3. This research provides a large-scale investigation of GC content in parasitic lice laying the foundation for understanding the basis of variation in base composition across species.

Massage Therapy Utilization in the Military Health System.

INTRODUCTION: Massage therapy is an evidence-based approach for pain management. Information regarding its utilization in the Military Health System (MHS) is lacking. The goal of this study is to evaluate massage therapy utilization patterns across the MHS to include who receives (patient characteristics and diagnoses) and provides (e.g., massage therapists) massage therapy and where (e.g., clinic type). MATERIALS AND METHODS: Medical record data of adult TRICARE Prime enrollees receiving outpatient massage therapy (Current Procedural Terminology codes: 97124 and 97140) from June 1, 2021, to May 31, 2023, were extracted from the MHS Data Repository. After identifying the index massage therapy visit, records for 6 months pre- and post-index were included. Descriptive statistics described massage therapy utilization patterns overall. Bivariate analysis compared patients who received massage therapy from massage therapists versus nonmassage therapist clinicians. RESULTS: Of patients who received massage therapy (n = 179,215), the median number of visits was 2 (interquartile range 1 to 4), the median age was 32 years (interquartile range 25 to 40), they were mostly assigned male (72%), White (53%), Senior Enlisted (51%), with a musculoskeletal diagnosis (90%), and recent non-steroidal anti-inflammatory drug (NSAID) prescription (58%). Massage therapy was primarily delivered by physical therapists (49%) in physical therapy clinics (74%). Massage therapists provided 0.2% of massage therapy. Patients who received massage therapy from massage therapists versus nonmassage therapists significantly varied across several patient and care characteristics. CONCLUSIONS: While massage therapy codes are documented frequently, massage therapists do not commonly provide massage therapy relative to nonmassage therapist providers. Access to massage therapists may be stymied by both lack of massage therapists and need for tertiary pain management referrals to access massage therapist-delivered care. Future research will leverage a health equity framework to (1) evaluate accessibility to massage therapy provided by massage therapists and (2) evaluate real-world evidence of massage therapy effectiveness.