Corrigendum: Reduced insulin signaling targeted to serotonergic neurons but not other neuronal subtypes extends lifespan in Drosophila melanogaster.

[This corrects the article DOI: 10.3389/fnagi.2022.893444.].

Quantum biological insights into CRISPR-Cas9 sgRNA efficiency from explainable-AI driven feature engineering.

CRISPR-Cas9 tools have transformed genetic manipulation capabilities in the laboratory. Empirical rules-of-thumb have been developed for only a narrow range of model organisms, and mechanistic underpinnings for sgRNA efficiency remain poorly understood. This work establishes a novel feature set and new public resource, produced with quantum chemical tensors, for interpreting and predicting sgRNA efficiency. Feature engineering for sgRNA efficiency is performed using an explainable-artificial intelligence model: iterative Random Forest (iRF). By encoding quantitative attributes of position-specific sequences for Escherichia coli sgRNAs, we identify important traits for sgRNA design in bacterial species. Additionally, we show that expanding positional encoding to quantum descriptors of base-pair, dimer, trimer, and tetramer sequences captures intricate interactions in local and neighboring nucleotides of the target DNA. These features highlight variation in CRISPR-Cas9 sgRNA dynamics between E. coli and H. sapiens genomes. These novel encodings of sgRNAs enhance our understanding of the elaborate quantum biological processes involved in CRISPR-Cas9 machinery.

Reduced Insulin Signaling Targeted to Serotonergic Neurons but Not Other Neuronal Subtypes Extends Lifespan in Drosophila melanogaster.

Reduced Insulin/IGF-like signaling (IIS) plays an evolutionarily conserved role in improving longevity and some measures of health-span in model organisms. Recent studies, however, have found a disconnection between lifespan extension and behavioral health-span. We have previously shown that reduction of IIS in Drosophila neurons extends female lifespan but does not improve negative geotaxis senescence and has a detrimental effect on exploratory walking senescence in both sexes. We hypothesize that individual neuronal subtypes respond differently to IIS changes, thus the behavioral outcomes of pan-neuronal IIS reduction are the balance of positive, negative and neutral functional effects. In order to further understand how reduced IIS in neurons independently modulates lifespan and locomotor behavioral senescence we expressed a dominant negative Insulin receptor transgene selectively in individual neuronal subtypes and measured the effects on lifespan and two measures of locomotor senescence, negative geotaxis and exploratory walking. IIS reduction in cholinergic, GABAergic, dopaminergic, glutamatergic, and octopaminergic neurons was found to have either no affect or a detrimental effect on lifespan and locomotor senescence. However, reduction of IIS selectively in serotonergic neurons resulted in extension of lifespan in females with no effect on locomotor senescence. These data indicate that individual neuronal subtypes respond differently to IIS changes in the modulation of lifespan and locomotor senescence, and identify a specific role for the insulin receptor in serotonergic neurons in the modulation of lifespan.

Septic Arthritis: Diagnosis and Treatment.

Septic arthritis must be considered and promptly diagnosed in any patient presenting with acute atraumatic joint pain, swelling, and fever. Risk factors for septic arthritis include age older than 80 years, diabetes mellitus, rheumatoid arthritis, recent joint surgery, hip or knee prosthesis, skin infection, and immunosuppressive medication use. A delay in diagnosis and treatment can result in permanent morbidity and mortality. Physical examination findings and serum markers, including erythrocyte sedimentation rate and C-reactive protein, are helpful in the diagnosis but are nonspecific. Synovial fluid studies are required to confirm the diagnosis. History and Gram stain aid in determining initial antibiotic selection. Staphylococcus aureus is the most common pathogen isolated in septic arthritis; however, other bacteria, viruses, fungi, and mycobacterium can cause the disease. After synovial fluid has been obtained, empiric antibiotic therapy should be initiated if there is clinical concern for septic arthritis. Oral antibiotics can be given in most cases because they are not inferior to intravenous therapy. Total duration of therapy ranges from two to six weeks; however, certain infections require longer courses. Consideration for microorganisms such as Neisseria gonorrhoeae, Borrelia burgdorferi, and fungal infections should be based on history findings and laboratory results.

Manual Therapy Informed by the Fascial Distortion Model for Plantar Heel Pain: Results of a Single-Arm Prospective Effectiveness Study.

Objectives: Plantar heel pain (PHP) is the most common cause of heel pain and can be debilitating; 20% of patients are refractory to standard of care. The Fascial Distortion Model (FDM), a novel manual diagnostic and treatment strategy, is purported to be effective for chronic pain; however, no rigorous studies document its effectiveness. We assessed the FDM for care of PHP. Design: Single arm prospective effectiveness study. Settings/Location: Outpatient primary care clinic; Fort Gordon, GA. Subjects: Outpatient adults. Interventions: Participants received an FDM-informed diagnostic and treatment strategy to identify fascial "distortions" at the foot based on patient-reported pain patterns and palpatory examination and then to provide distortion-specific manual therapy at baseline and 1 week. Outcome Measures: Primary outcome measure (0, 1, and 16 weeks): the Foot Pain subscale on the validated Foot Health Status Questionnaire (FHSQ; 0-100 points on each of eight separate subscales); secondary outcome measures (0, 1, and 16 weeks): the seven remaining subscales on the FHSQ, visual analog pain scale (VAS, 0-100 points), and plantar fascia thickness of the most effected foot assessed by ultrasound (0 and 16 weeks). Analysis was performed per protocol using repeated-measures analysis of variance. Results: One hundred and ninety-seven participants were screened; 33 were enrolled. Twenty-eight participants received two FDM procedures. Compared with baseline, improvement on the FHSQ Foot Pain (33.8-23.6 points) and Foot Function (23.9-19.8 points) subscales and VAS (44.7-27.7 points) at 16 weeks was statistically significant (all p's < 0.001) and clinically important representing large effect sizes. Relative to baseline, 16-week ultrasound demonstrated reduced average plantar fascia thickness (0.6-0.9 mm [p = 0.001]). Demographic characteristics were unrelated to response. Satisfaction was high. There were no serious adverse events; side effects included consistent mild-to-moderate self-limited pain. Conclusions: Participants with PHP who received FDM-informed care reported significant and sustained improvement on validated foot pain and foot function measures; additional findings included decreased plantar fascial thickness. These results require corroboration in a larger randomized controlled study. Clinical Trial Registration No: DDEAMC17005.

Major General Malcolm C. Grow, M.D. (1887-1960) Soldier, Surgeon, Airman.

World War I (WWI) and World War II (WWII) both presented physicians with challenges unseen before in history. New inventions such as the machine gun and poisonous gas in WWI and the massive aircraft battles in WWII required physicians and surgeons to adapt and innovate to provide the best care and preventative measures for service members. One physician, Malcolm Cummings Grow, distinguished himself as an innovator, a researcher, and a leader. His contributions to the field of military medicine, flight surgery, and medical administration led to countless lives being saved during the two World Wars and laid the groundwork for many different combat protective equipment still in use today.