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1. Characteristics of H7N9 avian influenza pneumonia: a retrospective analysis of 17 cases

   https://doi.org/10.1111/imj.14685  

   Yu, Wen‐Qing ; Ji, Ning‐Fei ; Ding, Ming‐Dong ; Gu, Cheng‐Jing ; Ma, Yuan ; Wu, Zhen‐Zhen ; Wang, Yan‐Li ; Wu, Chao‐Jie ; Dai, Gui‐Hong ; Chen, Yan ; et al ( September 2020 , Internal Medicine Journal)

   H7N9 avian influenza is an infection of public health concern, in part because of its high mortality rate and pandemic potential.

   To describe the clinical features of H7N9 avian influenza and the response to treatment.

   Clinical, radiological and histopathological data, and treatment‐related of H7N9‐infected patients hospitalised during 2014–2017 were extracted and analysed.

   A total of 17 H7N9 patients (three females; mean age, 58.4 ± 13.7 years) was identified; of these six died. All patients presented with fever and productive cough; four patients had haemoptysis and 13 had chest distress and/or shortness of breath. Early subnormal white blood cell count and elevation of serum liver enzymes were common. Multilobar patchy shadows, rapid progression to ground‐glass opacities, air bronchograms and consolidation were the most common imaging findings. Histopathological examination of lung tissue of three patients who died showed severe alveolar epithelial cell damage, with inflammatory exudation into the alveolar space and hyaline membrane formation; widened alveolar septae, prominent inflammatory cell infiltration; and hyperplasia of pneumocytes. Viral inclusions were found in the lung tissue of two patients. All patients received antiviral drugs (oseltamivir ± peramivir). Four patients carried the rs12252‐C/C interferon‐induced transmembrane protein‐3 (IFITM3) genotype, while the others had the C/T genotype.

   H7N9 virus infection causes human influenza‐like symptoms, but may rapidly progress to severe pneumonia and even death. Clinicians should be alert to the possibility of H7N9 infection in high‐risk patients. The presence of theIFITM3rs12252‐C genotype may predict severe illness.

    

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2. Novel Preoperative Risk Stratification Using Digital Phenotyping Applying a Scalable Machine-Learning Approach

   https://doi.org/10.1213/ANE.0000000000006753  

   Laferrière-Langlois, Pascal ; Imrie, Fergus ; Geraldo, Marc-Andre ; Wingert, Theodora ; Lahrichi, Nadia ; van der Schaar, Mihaela ; Cannesson, Maxime ( December 2023 , Anesthesia & Analgesia)

   Classification of perioperative risk is important for patient care, resource allocation, and guiding shared decision-making. Using discriminative features from the electronic health record (EHR), machine-learning algorithms can create digital phenotypes among heterogenous populations, representing distinct patient subpopulations grouped by shared characteristics, from which we can personalize care, anticipate clinical care trajectories, and explore therapies. We hypothesized that digital phenotypes in preoperative settings are associated with postoperative adverse events including in-hospital and 30-day mortality, 30-day surgical redo, intensive care unit (ICU) admission, and hospital length of stay (LOS).

   We identified all laminectomies, colectomies, and thoracic surgeries performed over a 9-year period from a large hospital system. Seventy-seven readily extractable preoperative features were first selected from clinical consensus, including demographics, medical history, and lab results. Three surgery-specific datasets were built and split into derivation and validation cohorts using chronological occurrence. Consensusk-means clustering was performed independently on each derivation cohort, from which phenotypes’ characteristics were explored. Cluster assignments were used to train a random forest model to assign patient phenotypes in validation cohorts. We reconducted descriptive analyses on validation cohorts to confirm the similarity of patient characteristics with derivation cohorts, and quantified the association of each phenotype with postoperative adverse events by using the area under receiver operating characteristic curve (AUROC). We compared our approach to American Society of Anesthesiologists (ASA) alone and investigated a combination of our phenotypes with the ASA score.

   A total of 7251 patients met inclusion criteria, of which 2770 were held out in a validation dataset based on chronological occurrence. Using segmentation metrics and clinical consensus, 3 distinct phenotypes were created for each surgery. The main features used for segmentation included urgency of the procedure, preoperative LOS, age, and comorbidities. The most relevant characteristics varied for each of the 3 surgeries. Low-risk phenotype alpha was the most common (2039 of 2770, 74%), while high-risk phenotype gamma was the rarest (302 of 2770, 11%). Adverse outcomes progressively increased from phenotypes alpha to gamma, including 30-day mortality (0.3%, 2.1%, and 6.0%, respectively), in-hospital mortality (0.2%, 2.3%, and 7.3%), and prolonged hospital LOS (3.4%, 22.1%, and 25.8%). When combined with the ASA score, digital phenotypes achieved higher AUROC than the ASA score alone (hospital mortality: 0.91 vs 0.84; prolonged hospitalization: 0.80 vs 0.71).

   For 3 frequently performed surgeries, we identified 3 digital phenotypes. The typical profiles of each phenotype were described and could be used to anticipate adverse postoperative events.

    

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3. Cold Storage Followed by Transplantation Induces Immunoproteasome in Rat Kidney Allografts: Inhibition of Immunoproteasome Does Not Improve Function

   https://doi.org/10.34067/KID.0000000000000368  

   Bhattarai, Dinesh ; Lee, Seong-ok ; Joshi, Neelam ; Jun, Se-Ran ; Lo, Sorena ; Jiang, Li ; Gokden, Neriman ; Parajuli, Nirmala ( February 2024 , Kidney360)

   It is a major clinical challenge to ensure the long-term function of transplanted kidneys. Specifically, the injury associated with cold storage of kidneys compromises the long-term function of the grafts after transplantation. Therefore, the molecular mechanisms underlying cold-storage–related kidney injury are attractive therapeutic targets to prevent injury and improve long-term graft function. Previously, we found that constitutive proteasome function was compromised in rat kidneys after cold storage followed by transplantation. Here, we evaluated the role of the immunoproteasome (iproteasome), a proteasome variant, during cold storage (CS) followed by transplantation.

   Established in vivo rat kidney transplant model with or without CS containing vehicle or iproteasome inhibitor (ONX 0914) was used in this study. Theiproteasome function was performed using rat kidney homogenates and fluorescent-based peptide substrate specific to β5i subunit. Western blotting and quantitative RT-PCR were used to assess the subunit expression/level of theiproteasome (β5i) subunit.

   We demonstrated a decrease in the abundance of the β5i subunit of theiproteasome in kidneys during CS, but β5i levels increased in kidneys after CS and transplant. Despite the increase in β5i levels and its peptidase activity within kidneys, inhibiting β5i during CS did not improve graft function after transplantation.

   These results suggest that the pharmacological inhibition of immunoproteasome function during CS does not improve graft function or outcome. In light of these findings, future studies targeting immunoproteasomes during both CS and transplantation may define the role of immunoproteasomes on short- and long-term kidney transplant outcomes.

    

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4. Dietary and plasma carotenoids are positively associated with alpha diversity in the fecal microbiota of pregnant women

   https://doi.org/10.1111/1750-3841.15586  

   Schmidt, Kristen M. ; Haddad, Eliot N. ; Sugino, Kameron Y. ; Vevang, Karin R. ; Peterson, Lisa A. ; Koratkar, Revati ; Gross, Myron D. ; Kerver, Jean M. ; Comstock, Sarah S. ( January 2021 , Journal of Food Science)

   Because microbes use carotenoids as an antioxidant for protection, dietary carotenoids could be associated with gut microbiota composition. We aimed to determine associations among reported carotenoid intake, plasma carotenoid concentrations, and fecal bacterial communities in pregnant women. Pregnant women (n= 27) were enrolled in a two‐arm study designed to assess feasibility of biospecimen collection and delivery of a practical nutrition intervention. Plasma and fecal samples were collected and women were surveyed with a 24‐hr dietary checklist and recalls. Plasma carotenoids were analyzed by HPLC using photodiode array detection. Fecal bacteria were analyzed by 16S rRNA DNA sequencing. Results presented are cross‐sectional from the 36‐week gestational study visit combined across both study arms due to lack of significant differences between intervention and usual care groups (n= 23 women with complete data). Recent intake of carotenoid‐containing foods included carrots, sweet potatoes, mangos, apricots, and/or bell peppers for 48% of women; oranges/orange juice (17%); egg (39%); tomato/tomato‐based sauces (52%); fruits (83%); and vegetables (65%). Average plasma carotenoid concentrations were 6.4 µg/dL α‐carotene (AC), 17.7 µg/dL β‐carotene (BC), 11.4 µg/dL cryptoxanthin, 39.0 µg/dL trans‐lycopene, and 29.8 µg/dL zeaxanthin and lutein. AC and BC concentrations were higher in women who recently consumed foods high in carotenoids. CR concentrations were higher in women who consumed oranges/orange juice. Microbiota α‐diversity positively correlated with AC and BC. Microbiota β‐diversity differed significantly across reported intake of carotenoid containing foods and plasma concentrations of AC. This may reflect an effect of high fiber or improved overall dietary quality, rather than a specific effect of carotenoids.

   Little is known about the association between the gut microbiome and specific dietary microconstituents, such as carotenoids, especially during pregnancy. This research demonstrates that a carotenoid‐rich diet during pregnancy supports a diverse microbiota, which could be one mechanism by which carotenoids promote health.

    

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5. Acute phase response to exertional heat stroke in mice

   https://doi.org/10.1113/EP088501  

   Iwaniec, John ; Robinson, Gerard P. ; Garcia, Christian K. ; Murray, Kevin O. ; de Carvalho, Lucas ; Clanton, Thomas L. ; Laitano, Orlando ( May 2020 , Experimental Physiology)

   What is the central question of this study?

   Exertional heat stroke is accompanied by a marked inflammatory response. In this study, we explored the time course of acute phase proteins during recovery from severe heat stress in mice and the potential role of skeletal muscles as their source.

   What is the main finding and its importance?

   Exertional heat stroke transiently increased expression of acute phase proteins in mouse liver and plasma and depleted liver and plasma fibrinogen, a typical response to severe trauma. In contrast, skeletal muscle fibrinogen production was stimulated by heat stroke, which can provide an additional reservoir for fibrinogen supply to maintain the clotting potential throughout the body and locally within the muscle.

   Exertional heat stroke (EHS), the most severe manifestation of heat illness, is accompanied by a marked inflammatory response. The release of acute phase proteins (APPs) is an important component of inflammation, which can assist in tissue survival/repair. The time course of APPs in recovery from EHS is unknown. Furthermore, skeletal muscles produce APPs during infection, but it is unknown whether they can produce APPs after EHS. Our objective was to determine the time course of representative APPs in liver, plasma and skeletal muscle during recovery from EHS. Male C57BL6/J mice ran in a forced running wheel at 37.5°C, 40% relative humidity until symptom limitation. Exercise control (EXC) mice ran for the same duration and intensity at 22.5°C. Samples were collected (n = 6–12 per group) over 14 days of recovery. Protein abundance was quantified using immunoblots. Total and phosphorylated STAT3 (pSTAT3) at Tyr705, responsible for APP activation, increased in liver at 0.5 h after EHS compared with EXC, (P < 0.05 andP < 0.001, respectively). In contrast, in tibialis anterior (TA) muscle, total STAT3 increased at 3 h (P < 0.05) but pSTAT3 (Tyr705) did not. Liver serum amyloid A1 (SAA1) increased at 3 and 24 h after EHS (P < 0.05), whereas plasma SAA1 increased only at 3 h (P < 0.05). SAA1 was not detected in TA muscle. In liver and plasma, fibrinogen decreased at 3 h (P < 0.01) and increased in TA muscle (P < 0.05). Lipocalin‐2 was undetectable in liver or TA muscle. Recovery from EHS is characterized by a transient acute phase response in both liver and skeletal muscle. However, APP expression profiles and subtypes differ between skeletal muscle and liver.

    

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