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Context.--The pathologic diagnosis of pulmonary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) is challenging. Objective.--To evaluate the diagnostic usefulness and limitations of current diagnostic strategies for pulmonary MALT lymphoma. Design.--A retrospective review of 120 cases of pulmonary MALT lymphoma from 2014 through 2021 was performed. Results.--Clinicoradiologic presentations overlapped with previous observations in patients with MALT lymphoma, such as a wide age range, female predominance, frequent association with autoimmune disease or immunodeficiency, and broad imaging findings. The histopathologic diagnosis was based on a combination of morphology, immunohistochemistry, and demonstration of B-cell lineage clonality. Two-thirds (76 of 113) of MALT lymphomas had lympho-plasmacytoid cytomorphology. Occasionally, MALT lymphomas were associated with granulomas/giant cells (29%, 35 of 120) or immunoglobulin deposition disease (21%, 25 of 120), including light chain/heavy chain deposition disease, amyloidosis, and/or crystal storing histiocytosis. While CD5, CD10, Bcl-2, and Bcl-6 rarely revealed aberrancies, aberrant CD43 expression either on B-cells or on plasma cells was detected in 42% (27 of 64) of cases, including cases for which proof of clonality could not be obtained. [kappa]/[lambda] in situ hybridization was particularly useful for tumors with lymphoplasmacytoid morphology but performed poorly in lymphomas having no plasmacytic differentiation. [kappa]/[lambda] immunohistochemistry showed no additional usefulness when applied together with [kappa]/[lambda] in situ hybridization. Immunoglobulin gene rearrangement studies by polymerase chain reaction achieved high detection rates of clonality in all cytomorphologic subgroups. Conclusions.--Our study offers a practical evaluation of common diagnostic tests in pulmonary MALT lymphoma. We offer recommendations for a diagnostic workup that takes into consideration the usefulness and the specific limitations of the various diagnostic strategies. doi: 10.5858/arpa.2022-0521-OA, Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) represents the most common type of primary lymphoma of the lung. As at other anatomic sites, MALT lymphoma of the [...]

Abstract Myeloperoxidase (MPO) is the most specific marker of the myeloid lineage, essential for diagnosing acute myeloid leukemia and mixed phenotype acute leukemia with myeloid components. In this regard, we present a unique case of B‐acute lymphoblastic leukemia (B‐ALL) with isolated MPO expression in bone marrow blasts detected by flow cytometry and immunohistochemistry, while peripheral blood blasts were negative for MPO expression. In this report, our discussion encompasses diagnostic pitfalls from a laboratory testing perspective in similar cases and includes a literature review. Furthermore, we emphasize the necessity of conducting a comprehensive analysis for the accurate diagnosis of MPO‐positive B‐ALL cases.

Abstract Lyme disease is a tick-borne disease caused by bacteria of the genus Borrelia. The host factors that modulate susceptibility for Lyme disease have remained mostly unknown. Using epidemiological and genetic data from FinnGen and Estonian Biobank, we identify two previously known variants and an unknown common missense variant at the gene encoding for Secretoglobin family 1D member 2 (SCGB1D2) protein that increases the susceptibility for Lyme disease. Using live Borrelia burgdorferi (Bb) we find that recombinant reference SCGB1D2 protein inhibits the growth of Bb in vitro more efficiently than the recombinant protein with SCGB1D2 P53L deleterious missense variant. Finally, using an in vivo murine infection model we show that recombinant SCGB1D2 prevents infection by Borrelia in vivo. Together, these data suggest that SCGB1D2 is a host defense factor present in the skin, sweat, and other secretions which protects against Bb infection and opens an exciting therapeutic avenue for Lyme disease.

E-cigarette or vaping product use-associated lung injury (EVALI) is a severe pulmonary illness associated with the use of e-cigarettes or vaping products that was officially identified and named in 2019. This American Thoracic Society workshop was convened in 2021 to identify and prioritize research and regulatory needs to adequately respond to the EVALI outbreak and to prevent similar instances of disease associated with e-cigarette or vaping product use. An interdisciplinary group of 26 experts in adult and pediatric clinical care, public health, regulatory oversight, and toxicology were convened for the workshop. Four major topics were examined: 1) the public health and regulatory response to EVALI; 2) EVALI clinical care; 3) mechanisms contributing to EVALI; and 4) needed actions to address the health effects of EVALI. Oral presentations and group discussion were the primary modes used to identify top priorities for addressing EVALI. Initiatives including a national EVALI case registry and biorepository, integrated electronic medical record coding system, U.S. Food and Drug Administration regulation and enforcement of nicotine e-cigarette standards, regulatory authority over nontobacco-derived e-cigarettes, training in evaluating exogenous exposures, prospective clinical studies, standardized clinical follow-up assessments, ability to more readily study effects of cannabinoid e-cigarettes, and research to identify biomarkers of exposure and disease were identified as critical needs. These initiatives will require substantial federal investment as well as changes to regulatory policy. Overall, the workshop identified the need to address the root causes of EVALI to prevent future outbreaks. An integrated approach from multiple perspectives is required, including public health; clinical, basic, and translational research; regulators; and users of e-cigarettes. Improving the public health response to reduce the risk of another substantial disease-inducing event depends on coordinated actions to better understand the inhalational toxicity of these products, informing the public of the risks, and developing and enforcing regulatory standards for all e-cigarettes.

IntroductionSmartphone use during caregiving has become increasingly common, especially around infants and very young children, and this use around young children has been linked with lower quality and quantity of parent-child interaction, with potential implications for child behavior, and parent-child attachment. To understand drivers and consequences of parent phone use, we were interested in the daily associations between parent phone use and depressed mood, as well as the potential for parent perceptions of their responsiveness toward their infant to alter the association between parent phone use and mood.MethodsIn the present study, we explored associations between day-to-day changes in parent smartphone use (objectively-measured via passive sensing) around their infant, depressed mood, and parent perceptions of their responsiveness to their infants among a sample of 264 parents across 8 days. We utilized multilevel modeling to examine these within-person daily associations.ResultsObjectively-measured parent smartphone use during time around their infant was significantly associated with depressed mood on a daily basis. Interestingly, this was not true on days when parents perceived themselves to be more responsive to their infant.DiscussionThese results suggest that parent judgements and perceptions of their parenting behavior may impact the potential link between parent phone use and parent mood. This is the first study utilizing intensive daily data to examine how parent perceptions may alter the felt effects of phone use on their parenting. Future work examining potential impacts of smartphone use on parenting should consider the effects of both actual use and perceptions about that use.

Over the past twenty-five years, the Medical Library Association (MLA) has pursued a range of diversity, equity, and inclusion (DEI) initiatives. This article, written by members of the Journal of the Medical Library Association (JMLA)’s Equity Advisory Group (EAG), outlines significant measures taken to raise awareness about specific concepts, opportunities, and challenges related to DEI among MLA members. Topics discussed include the impact of influential Black, Indigenous, and people of color (BIPOC) leaders, the establishment of DEI and social justice-focused membership communities, and specific initiatives led by various working groups and committees which have served to strengthen MLA’s commitment to diversity, equity, and inclusion during the last three decades.

The plastid-targeted transcription factor Whirly1 (WHY1) has been implicated in chloroplast biogenesis, plastid genome stability, and fungal defense response, which together represent characteristics of interest for the study of autotrophic losses across the angiosperms. While gene loss in the plastid and nuclear genomes has been well studied in mycoheterotrophic plants, the evolution of the molecular mechanisms impacting genome stability is completely unknown. Here, we characterize the evolution of WHY1 in four early transitional mycoheterotrophic orchid species in the genus Corallorhiza by synthesizing the results of phylogenetic, transcriptomic, and comparative genomic analyses with WHY1 genomic sequences sampled from 21 orders of angiosperms. We found an increased number of non-canonical WHY1 isoforms assembled from all but the greenest Corallorhiza species, including intron retention in some isoforms. Within Corallorhiza, phylotranscriptomic analyses revealed the presence of tissue-specific differential expression of WHY1 in only the most photosynthetically capable species and a coincident increase in the number of non-canonical WHY1 isoforms assembled from fully mycoheterotrophic species. Gene- and codon-level tests of WHY1 selective regimes did not infer significant signal of either relaxed selection or episodic diversifying selection in Corallorhiza but did so for relaxed selection in the late-stage full mycoheterotrophic orchids Epipogium aphyllum and Gastrodia elata. Additionally, nucleotide substitutions that most likely impact the function of WHY1, such as nonsense mutations, were only observed in late-stage mycoheterotrophs. We propose that our findings suggest that splicing and expression changes may precede the selective shifts we inferred for late-stage mycoheterotrophic species, which therefore does not support a primary role for WHY1 in the transition to mycoheterotrophy in the Orchidaceae. Taken together, this study provides the most comprehensive view of WHY1 evolution across the angiosperms to date.

Impulsivity undergoes a normative developmental trajectory from childhood to adulthood and is thought to be driven by maturation of brain structure. However, few large-scale studies have assessed associations between impulsivity, brain structure, and genetic susceptibility in children. In 9112 children ages 9–10 from the ABCD study, we explored relationships among impulsivity (UPPS-P impulsive behavior scale; delay discounting), brain structure (cortical thickness (CT), cortical volume (CV), and cortical area (CA)), and polygenic scores for externalizing behavior (PGSEXT). Both higher UPPS-P total scores and more severe delay-discounting had widespread, low-magnitude associations with smaller CA in frontal and temporal regions. No associations were seen between impulsivity and CV or CT. Additionally, higher PGSEXT was associated with both higher UPPS-P scores and with smaller CA and CV in frontal and temporal regions, but in non-overlapping cortical regions, underscoring the complex interplay between genetics and brain structure in influencing impulsivity. These findings indicate that, within large-scale population data, CA is significantly yet weakly associated with each of these impulsivity measures and with polygenic risk for externalizing behaviors, but in distinct brain regions. Future work should longitudinally assess these associations through adolescence, and examine associated functional outcomes, such as future substance use and psychopathology.

Abstract Bivalent molecules consisting of groups connected through bridging linkers often exhibit strong target binding and unique biological effects. However, developing bivalent inhibitors with the desired activity is challenging due to the dual motif architecture of these molecules and the variability that can be introduced through differing linker structures and geometries. We report a set of alternatively linked bivalent EGFR inhibitors that simultaneously occupy the ATP substrate and allosteric pockets. Crystal structures show that initial and redesigned linkers bridging a trisubstituted imidazole ATP-site inhibitor and dibenzodiazepinone allosteric-site inhibitor proved successful in spanning these sites. The re-engineered linker yielded a compound that exhibited significantly higher potency (~60 pM) against the drug-resistant EGFR L858R/T790M and L858R/T790M/C797S, which was superadditive as compared with the parent molecules. The enhanced potency is attributed to factors stemming from the linker connection to the allosteric-site group and informs strategies to engineer linkers in bivalent agent design.

The longevity of current joint replacements is limited by aseptic loosening, which is the primary cause of non-infectious failure for hip, knee, and ankle arthroplasty. Aseptic loosening is typically caused either by osteolysis from particulate wear, or by high shear stresses at the bone-implant interface from over-constraint. Our objective was to demonstrate feasibility of a compliant intramedullary stem that eliminates over-constraint without generating particulate wear. The compliant stem is built around a compliant mechanism that permits rotation about a single axis. We first established several models to understand the relationship between mechanism geometry and implant performance under a given angular displacement and compressive load. We then used a neural network to identify a design space of geometries that would support an expected 100-year fatigue life inside the body. We additively manufactured one representative mechanism for each of three anatomic locations, and evaluated these prototypes on a KR-210 robot. The neural network predicts maximum stress and torsional stiffness with 2.69% and 4.08% error respectively, relative to finite element analysis data. We identified feasible design spaces for all three of the anatomic locations. Simulated peak stresses for the three stem prototypes were below the fatigue limit. Benchtop performance of all three prototypes was within design specifications. Our results demonstrate the feasibility of designing patient- and joint-specific compliant stems that address the root causes of aseptic loosening. Guided by these results, we expect the use of compliant intramedullary stems in joint reconstruction technology to increase implant lifetime.

Abstract Background This study included evaluation of the effectiveness of vortioxetine, a treatment for adults with major depressive disorder (MDD), using patient-reported outcome measures (PROMs) in a real-world setting. Methods This retrospective chart review analyzed the care experiences of adult patients with a diagnosis of MDD from Parkview Physicians Group – Mind-Body Medicine, Midwestern United States. Patients with a prescription for vortioxetine, an initial baseline visit, and ≥ 2 follow-up visits within 16 weeks from September 2014 to December 2018 were included. The primary outcome measure was effectiveness of vortioxetine on depression severity as assessed by change in Patient Health Questionnaire-9 (PHQ-9) scores ~ 12 weeks after initiation of vortioxetine. Secondary outcomes included changes in depression-related symptoms (i.e., sexual dysfunction, sleep disturbance, cognitive function, work/social function), clinical characteristics, response, remission, and medication persistence. Clinical narrative notes were also analyzed to examine sleep disturbance, sexual dysfunction, appetite, absenteeism, and presenteeism. All outcomes were examined at index (start of vortioxetine) and at ~ 12 weeks, and mean differences were analyzed using pairwise t tests. Results A total of 1242 patients with MDD met inclusion criteria, and 63.9% of these patients had ≥ 3 psychiatric diagnoses and 65.9% were taking ≥ 3 medications. PHQ-9 mean scores decreased significantly from baseline to week 12 (14.15 ± 5.8 to 9.62 ± 6.03, respectively; p

This study in dogs had two objectives: first, to determine whether a daily supplement of marine omega-3 (EPA and DHA) would (1) increase red blood cell EPA + DHA levels (i.e., the Omega-3 Index derived from dried blood spot analysis) and (2) impact health-related measures. Dogs were recruited from five private veterinary clinics in the United States and supplemented with about 70 mg of EPA + DHA per kg body weight (BW) for 16 weeks. Health-related outcomes included quality of life (QOL) and pain scores using validated questionnaires. Twenty-nine dogs (8.4 ± 3.6 years old) finished this study. After 16 weeks of supplementation with 68 ± 19 mg EPA + DHA/kg/day, the O3I increased from 1.4% ± 1.0% at baseline to 3.3% ± 1.1% (p = p = 0.012), primarily in small and medium-sized dogs. QOL scores improved slightly but only in small dogs (p = 0.03). Thus, supplementation with about 70 mg of EPA + DHA/kg/day improved the O3I and, in smaller dogs, pain and QOL scores. Future studies are needed to more clearly define doses of EPA + DHA that would improve the health of dogs.

Introduction: Previous studies suggest improved intubation success using video laryngoscopy (VL) vs direct laryngoscopy (DL), yet recent randomized trials have not shown clear benefit of one method over the other. These studies, however, have generally excluded difficult airways and rapid sequence intubation. In this study we looked to compare first-pass success (FPS) rates between VL and DL in adult emergency department (ED) patients with difficult airways.  Methods: We conducted a secondary analysis of prospectively collected observational data in the National Emergency Airway Registry (NEAR) (January 2016–December 2018). Variables included demographics, indications, methods, medications, devices, difficult airway characteristics, success, and adverse events. We included adult ED patients intubated with VL or DL who had difficult airways identified by gestalt or anatomic predictors. We stratified VL by hyperangulated (HAVL) vs standard geometry VL (SGVL). The primary outcome was FPS, and the secondary outcome was comparison of adverse event rates between groups. Data analyses included descriptive statistics with cluster-adjusted 95% confidence intervals (CI). Results: Of 18,123 total intubations, 12,853 had a predicted or identified anatomically difficult airway. The FPS for difficult airways was 89.1% (95% CI 85.9-92.3) with VL and 77.7% (95% CI 75.7-79.7) with DL (P