bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum N-glycomics of a novel CDG-IIb patient reveals aberrant IgG glycosylation
Authors: Beimdiek Julia , Hennig René , Burock Robert , Puk Oliver , Biskup Saskia , Rapp Erdmann , Lesinski-Schiedat Anke , Buettner Falk F R , Das Anibh M
Published: February 2022

Rare genetic mutations of the mannosyl-oligosaccharide glucosidase (MOGS) gene affecting the function of the mannosyl-oligosaccharide glucosidase (glucosidase I) are the cause of the congenital disorder of glycosylation IIb (CDG-IIb). Glucosidase I specifically removes the distal α1,2-linked glucose from the protein bound precursor N-glycan Glc3Man9GlcNAc2, which is the initial step of N-glycan maturation. Here, we comparatively analyzed N-glycosylation of the whole serum proteome, serum-derived immunoglobulin G (IgG), transferrin (TF), and α-1-antitrypsin (AAT) of a female patient who is compound heterozygous for 2 novel missense mutations in the MOGS gene, her heterozygous parents, and a sibling with wildtype genotype by multiplexed capillary gel electrophoresis coupled to laser induced fluorescence detection (xCGE-LIF) at unprecedented depth. Thereby, we detected the CDG-IIb-characteristic non-de-glucosylated N-glycans Glc3Man7-9GlcNAc2 as well as the free tetrasaccharide Glc3-Man in whole serum of the patient but not in the other family members. The N-glycan analysis of the serum proteome further revealed that relative intensities of IgG-specific complex type di-antennary N-glycans with core-fucosylation were considerably reduced in the patient’s serum whereas TF- and AAT-characteristic sialylated di- and tri-antennary N-glycans were increased. This finding reflected the hypogammaglobulinemia diagnosed in the patient. We further detected aberrant oligo-mannose (Glc3Man7GlcNAc2) and hybrid type N-glycans on patient-derived IgGs and we attributed this defective glycosylation to be the reason for an increased IgG clearance. This mechanism can explain the hypogammaglobulinemia that is associated with CDG-IIb.
Non-canonical initiation factors modulate repeat-associated non-AUG translation
Authors: Green Katelyn M , Miller Shannon L , Malik Indranil , Todd Peter K
Published: February 2022

Repeat-associated non-AUG (RAN) translation of expanded repeat-mutation mRNA produces toxic peptides in neurons of patients suffering from neurodegenerative diseases. Recent findings indicate that RAN translation in diverse model systems is not inhibited by cellular stressors that impair global translation through phosphorylation of the alpha subunit of eIF2, the essential eukaryotic translation initiation factor that brings the initiator tRNA to the 40S ribosome. Using in vitro, cell-based and Drosophila models, we examined the role of alternative ternary complex factors that may function in place of eIF2, including eIF2A, eIF2D, DENR and MCTS1. Among these factors, DENR knockdown had the greatest inhibitory effect on RAN translation of expanded GGGGCC and CGG repeat reporters and its reduction improved the survival of Drosophila expressing expanded GGGGCC repeats. Taken together, these data support a role for alternative initiation factors in RAN translation and suggest these may serve as novel therapeutic targets in neurodegenerative disease.
Proteomic profiling identifies novel proteins for genetic risk of severe COVID-19: the Atherosclerosis Risk in Communities Study
Authors: Steffen Brian T , Pankow James S , Lutsey Pamela L , Demmer Ryan T , Misialek Jeffrey R , Guan Weihua , Cowan Logan T , Coresh Josef , Norby Faye L , Tang Weihong
Published: February 2022

Background

Genome-wide association studies have identified six genetic variants associated with severe COVID-19, yet the mechanisms through which they may affect disease remains unclear. We investigated proteomic signatures related to COVID-19 risk variants rs657152 (ABO), rs10735079 (OAS1/OAS2/OAS3), rs2109069 (DPP9), rs74956615 (TYK2), rs2236757 (IFNAR2) and rs11385942 (SLC6A20/LZTFL1/CCR9/FYCO1/CXCR6/XCR1) as well as their corresponding downstream pathways that may promote severe COVID-19 in risk allele carriers and their potential relevancies to other infection outcomes.

Methods

A DNA aptamer-based array measured 4870 plasma proteins among 11 471 participants. Linear regression estimated associations between the COVID-19 risk variants and proteins with correction for multiple comparisons, and canonical pathway analysis was conducted. Cox regression assessed associations between proteins identified in the main analysis and risk of incident hospitalized respiratory infections (2570 events) over a 20.7-year follow-up.

Results

The ABO variant rs657152 was associated with 84 proteins in 7241 white participants with 24 replicated in 1671 Black participants. The TYK2 variant rs74956615 was associated with ICAM-1 and -5 in white participants with ICAM-5 replicated in Black participants. Of the 84 proteins identified in the main analysis, seven were significantly associated with incident hospitalized respiratory infections including Ephrin type-A receptor 4 (hazard ratio (HR): 0.87; P = 2.3 × 10−11) and von Willebrand factor type A (HR: 1.17; P = 1.6x10−13).

Conclusions

Novel proteomics signatures and pathways for COVID-19-related risk variants TYK2 and ABO were identified. A subset of these proteins predicted greater risk of incident hospitalized pneumonia and respiratory infections. Further studies to examine these proteins in COVID-19 patients are warranted.
Evaluating Bactrocera dorsalis (Hendel) (Diptera: Tephritidae) Response to Methyl Eugenol: Comparison of Three Common Bioassay Methods
Authors: Sim Sheina B , Curbelo Keena M , Manoukis Nicholas C , Cha Dong H
Published: February 2022

Insect responses to chemical attractants are often measured using olfactory bioassays prior to testing in field experiments. The attraction of sexually mature male Bactrocera dorsalis to methyl eugenol (ME) and the loss of attraction by ME pre-fed males have been demonstrated in laboratory bioassays and field trapping studies. It has been suggested that ME nonresponsiveness can be exploited to improve the effectiveness of B. dorsalis management programs by protecting sterile males from ME-based control measures. Currently, work is underway to identify alternatives that reduce or eliminate ME response. To support the development of compounds and evaluation of their effect on B. dorsalis attraction to ME, we compared the effectiveness of three common bioassay methods that have been used to measure lure response in Bactrocera flies under controlled conditions (choice assays using Y-tube [Y], small-cage arena [SC], and rotating carousel field-cage [RC]) to determine which bioassay method is efficient and reliable. A series of bioassays comparing ME-exposed and ME-naïve wild-type and genetic sexing strain males showed that the RC and SC were effective at both observing attraction to ME and detecting a significant reduction in ME response from ME-exposed males. However, the male attraction to ME and a significant decrease in response to ME after ME feeding was not observed in our Y-tube assays. These suggest that RC and SC are preferable options to evaluate ME non-responsiveness in B. dorsalis, and that Y-tube tests are difficult to administer correctly.
Selection of Reference Genes for RT-qPCR Analysis in the Hawthorn Spider Mite, Amphitetranychus viennensis (Acarina: Tetranychidae), Under Acaricide Treatments
Authors: Zhang Yuying , Zhang Zhonghuan , Ren Meifeng , Liu Xiangying , Zhou Xuguo , Yang Jing
Published: February 2022

Hawthorn spider mite, Amphitetranychus viennensis Zacher, one of the most damaging arthropod pests for Rosaceaous fruit trees and ornamentals, has developed resistance to most of the commercially available acaricides. To understand the molecular basis of acaricide resistance, a standardized protocol for real-time quantitative reverse transcription PCR (RT-qPCR) following the MIQE (minimum information for publication of quantitative real time PCR experiments) guidelines is needed. In this study, we screened for the internal references in A. viennensis to study in acaricide resistance. In total, 10 candidate reference genes, including EF1A, 28S rRNA, 18S rRNA, α-tubulin, Actin3, RPS9, GAPDH, V-ATPase B, RPL13, and V-ATPase A, were assessed under the treatments of four commonly used acaricides with distinct mode-of-actions (MOAs). Based on the Insecticide Resistance Action Committee MOA classification, avermectin, bifenazate, spirodiclofen, and fenpropathrin belong to group 6, 20D, 23, and 3A, respectively. The expression profiles of these candidate genes were evaluated using geNorm, Normfinder, BestKeeper, and ∆Ct methods, respectively. Eventually, different sets of reference genes were recommended for each acaricide according to RefFinder, a comprehensive platform integrating all four above-mentioned algorithms. Specifically, the top three recommendations were 1) 28S, V-ATPase A, and Actin 3 for avermectin, 2) GAPDH, RPS9, and 28S for bifenazate, 3) Actin 3, V-ATPase B, and α-tubulin for spirodiclofen, and 4) Actin 3, α-tubulin, and V-ATPase A for fenpropathrin. Although unique sets of genes are proposed for each acaricide, α-tubulin, EF1A, and GAPDH are the most consistently stably expressed reference genes when A. viennensis was challenged chemically. Our findings lay the foundation for the study of acaricide resistance in the phytophagous mites in general, and in the hawthorn spider mite, A. viennensis, in particular.
Monitoring of Spotted-Wing Drosophila (Diptera: Drosophilidae) Resistance Status Using a RAPID Method for Assessing Insecticide Sensitivity Across the United States
Authors: Isaacs Rufus , Van Timmeren Steven , Gress Brian E , Zalom Frank G , Ganjisaffar Fatemeh , Hamby Kelly A , Lewis Margaret T , Liburd Oscar E , Sarkar Nupur , Rodriguez-Saona Cesar , Holdcraft Robert , Burrack Hannah J , Toennisson Aurora , Drummond Francis , Spaulding Nathan , Lanka Srinivas , Sial Ashfaq
Published: February 2022

Drosophila suzukii (Matsumura) has spread rapidly, challenging berry and cherry crop production due to its ability to lay eggs into ripening fruit. To prevent infestation by this pest, insecticides are applied during fruit ripening and harvest. We field-tested the Rapid Assessment Protocol for IDentification of resistance in D. suzukii (RAPID) on seventy-eight populations collected across eight U.S. states in 2017 and 2018. Exposure to LC50 rates of malathion, methomyl, spinetoram, spinosad, and zeta-cypermethrin led to average female fly mortality of 25.0% in 2017, and after adjusting concentrations the average was 39.9% in 2018. Using LC99 × 2 discriminating concentrations in 2017 and LC90 × 8 rates in 2018, average female mortalities were 93.3% and 98.5%, respectively, indicating high overall susceptibility. However, using these high concentrations we found 32.0% of assays with survival of some female flies in 2017 and 27.8% in 2018. The adjustment in discriminating dose from 2017 to 2018 also reduced the proportion of assays with <90% survival from 17.6 to 2.9%. Populations with low mortality when exposed to spinosad were identified using this assay, triggering more detailed follow-up bioassays that identified resistant populations collected in California coastal region berry crops. Widespread evaluations of this method and subsequent validation in California, Michigan, and Georgia in 2019–2021 show that it provides a quick and low-cost method to identify populations of D. suzukii that warrant more detailed testing. Our results also provide evidence that important insecticide classes remain effective in most U.S. regions of fruit production.
Captain Cook, Mrs Taylor and a Mi’kmaw quillwork box: An uncorroborated inscription, an unwarranted assertion and an imagined collection
Authors: Coote Jeremy
Published: February 2022

In 1963 a small box bearing an inscription stating that it had been ‘brought from Otaheite by Captn. Cook and presented by him to Mrs. Taylor Circus Bath’ was donated to the National Maritime Museum in London. That the box is actually an example of Mi’kmaw work from Nova Scotia has led previous scholars to claim that the famous navigator James Cook (1728–1779) made a collection of artefacts while he was on Royal Navy duty in Atlantic Canada in the years 1758 to 1767. An exploration of the evidence leads to two conclusions: that there is nothing to corroborate the inscription’s claim that Cook presented the box to Mrs Taylor; and that the related assertion that Cook made a collection in Atlantic Canada should be set aside.
PI3K/AKT/Nrf2 signalling pathway is involved in the ameliorative effects of xanthohumol on amyloid β-induced oxidative damage and bone loss
Authors: Xia Tianshuang , Liu Xiaoyan , Wang Nani , Jiang Yiping , Bai Huanhuan , Xu Weifan , Feng Kunmiao , Han Ting , Xin Hailiang
Published: February 2022

Objective

Xanthohumol (XAN), a natural isoflavone from Humulus lupulus L., possesses biological activities on relieving oxidative stress and osteoporosis (OP). This study aimed to evaluate the antioxidative and osteoprotective effect of XAN on Aβ-injured osteoblasts, and explore its underlying mechanism.

Methods

Osteoblasts were pretreated with XAN followed by stimulation with Aβ1–42. Cell proliferation, ALP activity, bone mineralization and bone formation index were measured. Apoptosis and reactive oxygen species (ROS) were analysed with flow cytometer. PI3K inhibitor LY294002 or siRNA-Nrf2 was added and transfected in osteoblasts, to further confirm whether the pathway participated in the regulation of XAN-induced cytoprotection.

Key findings

XAN markedly improved the proliferation, differentiation and mineralization of Aβ-injured osteoblasts. Additionally, XAN reduced cell apoptosis rate and ROS level, and increased the expression of p-AKT, Nrf2, NQO1, HO-1 and SOD-2. More importantly, LY294002 or siNrf2 abolished the beneficial effect of XAN on osteoblasts activity and decreased the PI3K expression and inhibited its downstream proteins, indicating XAN activated PI3K/AKT/Nrf2 pathway in Aβ-injured osteoblasts.

Conclusion

It was the first time to reveal the antioxidative and osteoprotective effect of XAN through regulating PI3K/AKT/Nrf2 pathway in Aβ-injured osteoblasts, which provides reference for the clinical application of XAN in the prevention and treatment of OP.
ORESARA 15, a PLATZ transcription factor, controls root meristem size through auxin and cytokinin signalling-related pathways
Authors: Timilsina Rupak , Kim Yongmin , Park Sanghoon , Park Hyunsoo , Park Sung-Jin , Kim Jin Hee , Park Ji-Hwan , Kim Doa , Park Youn-Il , Hwang Daehee , Lee Jong-Chan , Woo Hye Ryun
Published: February 2022

An optimal size of post-embryonic root apical meristem (RAM) is achieved by a balance between cell division and differentiation. Despite extensive research, molecular mechanisms underlying the coordination of cell division and differentiation are still fragmentary. Here, we report that ORESARA 15 (ORE15), an Arabidopsis PLANT A/T-RICH SEQUENCE-AND ZINC-BINDING PROTEIN (PLATZ) transcription factor preferentially expressed in the RAM, determines RAM size. Primary root length, RAM size, cell division rate, and stem cell niche activity were reduced in an ore15 loss-of-function mutant but enhanced in an activation-tagged line overexpressing ORE15, compared with wild type. ORE15 forms mutually positive and negative feedback loops with auxin and cytokinin signalling, respectively. Collectively, our findings imply that ORE15 controls RAM size by mediating the antagonistic interaction between auxin and cytokinin signalling-related pathways.
Targeted Next-Generation Sequencing Reveals Exceptionally High Rates of Molecular Driver Mutations in Never-Smokers With Lung Adenocarcinoma
Authors: Mack Philip C , Klein Michael I , Ayers Kristin L , Zhou Xiang , Guin Sunny , Fink Marc , Rossi Michael , AI-Kateb Hussam , O’Connell Timmy , Hantash Feras M , Oh William K , Newman Scott , Schadt Eric E , Chen Rong , Hirsch Fred R
Published: February 2022

Introduction

Historically, high rates of actionable driver mutations have been reported in never-smokers with lung adenocarcinoma (ADC). In the era of modern, comprehensive cancer mutation sequencing, this relationship necessitates a more detailed analysis.

Methods

All Mount Sinai patients between January 1, 2015, and June 1, 2020, with a diagnosis of ADC of any stage with known smoking status who received genomic testing were included. Most patients were analyzed using the Sema4 hotspot panel or the Oncomine Comprehensive Assay version 3 next-generation sequencing (NGS) panel conducted at Sema4. Patients were considered fully genotyped if they were comprehensively analyzed for alterations in EGFR, KRAS, MET, ALK, RET, ROS1, BRAF, NTRK1-3, and ERBB2, otherwise they were considered partially genotyped.

Results

Two hundred and thirty-six never-smokers and 671 smokers met the above criteria. Of the never-smokers, 201 (85%) had a driver mutation with 167 (71%) considered actionable (ie, those with US Food and Drug Administration-approved agents). Among smokers, 439 (65%) had an identified driver mutation with 258 (38%) actionable (P < .0001). When comprehensively sequenced, 95% (70/74) of never-smokers had a driver mutation with 78% (58/74) actionable; whereas, for smokers, 75% (135/180) had a driver with only 47% (74/180) actionable (P < .0001). Within mutations groups, EGFR G719X and KRAS G12Cs were more common to smokers. For stage IV patients harboring EGFR-mutant tumors treated with EGFR-directed therapies, never-smokers had significantly improved OS compared to smokers (hazard ratio = 2.71; P = .025). In multivariable analysis, Asian ancestry and female sex remained significant predictors of (1) OS in stage IV patients and (2) likelihood of harboring a receptor of fusion-based driver.

Conclusion

Comprehensive NGS revealed driver alterations in 95% of never-smokers, with the majority having an associated therapy available. All efforts should be exhausted to identify or rule out the presence of an actionable driver mutation in all metastatic lung ADC.
Migrations of Decolonization, Welfare, and the Unevenness of Citizenship in the UK, France and Portugal
Authors: Eldridge Claire , Kalter Christoph , Taylor Becky
Published: February 2022

Among its many global impacts, decolonization triggered the migration of several million ‘repatriates’ — white settlers or others associated with the imperial power — who left Asia and Africa and ‘returned’ to their European ‘motherlands’. This article explores the arrival of several thousand Anglo-Egyptians into Britain in 1957 following the Suez crisis, the one million pieds-noirs who left Algeria for France in 1962, and the 500,000 retornados who entered Portugal amidst the 1975 Carnation Revolution. Offering an integrated comparison of these three key moments of decolonization via the migrations they triggered, it underscores the importance of citizenship, understood here as both a ‘hard’ legal category and a set of ‘soft’ social practices. The comparison equally demonstrates how, across different national contexts, citizenship was unevenly applied. Despite holding the same rights, returnee-citizens faced discrimination from resident-citizens in subtle (and sometimes less subtle) ways. Moreover, subgroups of returnee-citizens were treated differently by the state, in a process that amounted at times to their physical and social segregation and a racialization of welfare. This unevenness of treatment illuminates how the British, French, and Portuguese national communities were reimagined in the era of decolonization, and the crucial role ‘repatriated’ citizens played in that process.
Perception of Resource Allocations to Address the Opioid Epidemic
Authors: Strickland Justin C. , Victor Grant , Ray Bradley
Published: February 2022

Objectives

Despite billions of dollars spent on opioid policy initiatives, public knowledge of evidence-based policies to reduce opioid-related morbidity remain low. Consequences of this knowledge gap for support of initiatives remains understudied. Our objective was to evaluate how participants with and without lived experience allocate funding for initiatives to address the opioid epidemic. A secondary objective was to collect proof-of-concept data of an informational intervention designed to improve support for evidence-based policies.

Methods

Participants (N = 284; 57.2% female) without lifetime nonmedical opioid use (n = 98) and those with lifetime use (past year [n = 81] or nonpast year [n = 105]) of nonmedical opioids were recruited. All participants reported how they would allocate funds to demand reduction, supply reduction, harm reduction, and treatment policies. Half of all participants were then randomized to a brief informational intervention designed to emphasize evidence-based harm reduction and treatment programs.

Results

Funding allocations were highest for policies related to community services and treatment and lowest for those related to harm reduction. Participants with lived experience allocated less to supply reduction policies. Participants (12%) who reallocated funds after information exposure increased funding to supervised consumption sites, d

z
= 0.77, naloxone distribution, d

z
= 0.85, syringe exchange programs, d

z
= 0.63, and medications for opioid use disorder access, d

z
= 0.70.

Conclusions

This study illustrates how people with and without lived experience prioritize various policies to address the opioid epidemic and emphasize comparably low support for harm reduction policies. Proof-of-concept data suggest that brief informational interventions may increase funding support for harm reduction strategies, at least in a subset of people.
Longitudinal Trends in Bleeding Complications on Extracorporeal Life Support Over the Past Two Decades—Extracorporeal Life Support Organization Registry Analysis
Authors: Willers Anne , Swol Justyna , Buscher Hergen , McQuilten Zoe , van Kuijk Sander M. J. , ten Cate Hugo , Rycus Peter T. , McKellar Stephen , Lorusso Roberto , Tonna Joseph E.
Published: February 2022

OBJECTIVES:

Data about inhospital outcomes in bleeding complications during extracorporeal life support (ECLS) have been poorly investigated.

DESIGN:

Retrospective observational study.

SETTING:

Patients reported in Extracorporeal Life Support Organization Registry.

PATIENTS:

Data of 53.644 adult patients (greater than or equal to 18 yr old) mean age 51.4 ± 15.9 years, 33.859 (64.5%) male supported with single ECLS run between 01.01.2000 and 31.03.2020, and 19.748 cannulated for venovenous (V-V) ECLS and 30.696 for venoarterial (V-A) ECLS.

INTERVENTIONS:

Trends in bleeding complications, bleeding risk factors, and mortality.

MEASUREMENT AND MAIN RESULTS:

Bleeding complications were reported in 14.786 patients (27.6%), more often in V-A ECLS compared with V-V (30.0% vs 21.9%; p < 0.001). Hospital survival in those who developed bleeding complications was lower in both V-V ECLS (49.6% vs 66.6%; p < 0.001) and V-A ECLS (33.9 vs 44.9%; p < 0.001). Steady decrease in bleeding complications in V-V and V-A ECLS was observed over the past 20 years (coef., –1.124; p < 0.001 and –1.661; p < 0.001). No change in mortality rates was reported over time in V-V or V-A ECLS (coef., –0.147; p = 0.442 and coef., –0.195; p = 0.139).

Multivariate regression revealed advanced age, ecls duration, surgical cannulation, renal replacement therapy, prone positioning as independent bleeding predictors in v-v ecls and female gender, ecls duration, pre-ecls arrest or bridge to transplant, therapeutic hypothermia, and surgical cannulation in v-a ecls.

CONCLUSIONS:

A steady decrease in bleeding over the last 20 years, mostly attributable to surgical and cannula-site–related bleeding has been found in this large cohort of patients receiving ECLS support. However, there is not enough data to attribute the decreasing trends in bleeding to technological refinements alone. Especially reduction in cannulation site bleeding is also due to changes in timing, patient selection, and ultrasound guided percutaneous cannulation. Other types of bleeding, such as CNS, have remained stable, and overall bleeding remains associated with a persistent increase in mortality.
Therapeutic Hyperthermia Is Associated With Improved Survival in Afebrile Critically Ill Patients With Sepsis: A Pilot Randomized Trial
Authors: Drewry Anne M. , Mohr Nicholas M. , Ablordeppey Enyo A. , Dalton Catherine M. , Doctor Rebecca J. , Fuller Brian M. , Kollef Marin H. , Hotchkiss Richard S.
Published: February 2022

OBJECTIVES:

To test the hypothesis that forced-air warming of critically ill afebrile sepsis patients improves immune function compared to standard temperature management.

DESIGN:

Single-center, prospective, open-label, randomized controlled trial.

SETTING:

One thousand two hundred-bed academic medical center.

PATIENTS:

Eligible patients were mechanically ventilated septic adults with: 1) a diagnosis of sepsis within 48 hours of enrollment; 2) anticipated need for mechanical ventilation of greater than 48 hours; and 3) a maximum temperature less than 38.3°C within the 24 hours prior to enrollment. Primary exclusion criteria included: immunologic diseases, immune-suppressing medications, and any existing condition sensitive to therapeutic hyperthermia (e.g., brain injury). The primary outcome was monocyte human leukocyte antigen (HLA)-DR expression, with secondary outcomes of CD3/CD28-induced interferon gamma (IFN-γ) production, mortality, and 28-day hospital-free days.

INTERVENTIONS:

External warming using a forced-air warming blanket for 48 hours, with a goal temperature 1.5°C above the lowest temperature documented in the previous 24 hours.

MEASUREMENTS AND MAIN RESULTS:

We enrolled 56 participants in the study. No differences were observed between the groups in HLA-DR expression (692 vs 2,002; p = 0.396) or IFN-γ production (31 vs 69; p = 0.678). Participants allocated to external warming had lower 28-day mortality (18% vs 43%; absolute risk reduction, 25%; 95% CI, 2–48%) and more 28-day hospital-free days (difference, 2.6 d; 95% CI, 0–11.6).

CONCLUSIONS:

Participants randomized to external forced-air warming did not have a difference in HLA-DR expression or IFN-γ production. In this pilot study, however, 28-day mortality was lower in the intervention group. Future research should seek to better elucidate the impact of temperature modulation on immune and nonimmune organ failure pathways in sepsis.
The Role of Zinc in Cardiovascular Disease
Authors: Begum Farhana , Me Hay Me , Christov Marta
Published: February 2022

Zinc is an essential trace element due to its role as a key part of human enzymatic activity. As a cofactor in metalloenzymes and metalloproteins, zinc participates in diverse biological functions, including gene transcription, translation, and replication, phagocytosis, and immunoglobulin and cytokine production. In this review, we will focus on the role of zinc in the cardiovascular system, including heart failure, vascular calcification, and myocardial infarction. We will further highlight the role of zinc in cardiovascular pathology in individuals with chronic kidney disease, and type II diabetes mellitus, groups uniquely at risk for cardiovascular morbidity and mortality.
NEMO-NDAS: A Panniculitis in the Young Representing an Autoinflammatory Disorder in Disguise
Authors: Hegazy Shaymaa , Marques Mariana C. , Canna Scott W. , Goldbach-Mansky Raphaela , de Jesus Adriana A. , Reyes-Múgica Miguel , Salgado Claudia M.
Published: February 2022

A 15-month-old full-term boy of African descent with an asymptomatic sickle cell trait presented with episodes of transient erythematous subcutaneous nodules involving the entire body except the face, since 2 weeks of age. The skin lesions evolved to areas of lipoatrophy and hyperpigmentation. An initial skin biopsy, studied at a different department at 2 months, was initially misinterpreted as subcutaneous fat necrosis of the newborn, despite the lack of the typical radiated crystals and needle-shaped clefts characterizing that entity. At 4 months of age, he developed systemic inflammatory manifestations, including fever, a new rash, significant periorbital edema, and failure to thrive. An extensive workup showed leukocytosis, hypercalcemia, elevated inflammatory markers, hypertriglyceridemia, and transaminitis. A new skin biopsy of the eyelid was diagnosed as neutrophilic lobular panniculitis with necrotic adipocytes. An initial whole-exome sequencing did not identify any causative mutations, but a WES reanalysis focused on autoinflammatory disorders was requested based on additional clinicopathologic data and revealed a mosaic intronic mutation in IKBKG c. 671+3 G > C. This mutation encodes an mRNA missing exon 5 resulting in NF-kB essential modulator (NEMO) Δ-exon 5–autoinflammatory syndrome (NDAS). NEMO-NDAS is one of the systemic autoinflammatory diseases that may appear as an unexplained panniculitis in young children, who should be monitored for immunodeficiency and/or autoinflammatory diseases. The differential diagnosis of autoinflammatory disorders should be considered in such cases incorporating the use of the whole-genome/exome sequencing in the investigation. The inhibitor of kappa-B kinase regulatory subunit gamma (IKBKG) is located on chromosome Xq28 and encodes the NEMO, a critical molecule upstream of NF-kB activation.
Length of PM2.5 exposure and alterations in the serum metabolome among women undergoing infertility treatment
Authors: Hood Robert B. , Liang Donghai , Tang Ziyin , Kloog Itai , Schwartz Joel , Laden Francine , Jones Dean , Gaskins Audrey J.
Published: February 2022

Background:

Both acute and chronic exposure to fine particulate matter (PM2.5) have been linked to negative health outcomes. Studies have used metabolomics to describe the biological pathways linking PM2.5 with disease but have focused on a single exposure window. We compared alterations in the serum metabolome following various short- and long-term PM2.5 exposures.

Methods:

Participants were women undergoing in vitro fertilization at a New England fertility clinic (n = 200). Women provided their residential address and provided a blood sample during controlled ovarian stimulation. PM2.5 exposure was estimated in the 1, 2, and 3 days, 2 weeks, and 3 months prior to blood collection using a validated spatiotemporal model. We utilized liquid chromatography with high-resolution mass spectrometry. We used generalized linear models to test for associations between metabolomic features and PM2.5 exposures after adjusting for potential confounders. Significant features (P < 0.005) were used for pathway analysis and metabolite identification.

Results:

We identified 17 pathways related to amino acid, lipid, energy, and nutrient metabolism that were solely associated with acute PM2.5 exposure. Fifteen pathways, mostly, pro-inflammatory, anti-inflammatory, amino acid, and energy metabolism, were solely associated with long-term PM2.5 exposure. Seven pathways were associated with the majority of exposure windows and were mostly related to anti-inflammatory and lipid metabolism. Among the significant features, we confirmed seven metabolites with level-1 evidence.

Conclusions:

We identified serum metabolites and metabolic pathways uniquely associated with acute versus chronic PM2.5 exposure. These different biologic pathways may help explain differences in disease states when investigating different lengths of PM2.5 exposure.
DMEK Without Postoperative Supine Posturing
Authors: Parker Jack S. , Parker John S. , Tate Hudson , Melles Gerrit R. J.
Published: February 2022

Purpose:

The purpose of this study was to describe the incidence of graft detachment after Descemet membrane endothelial keratoplasty (DMEK) without postoperative supine posturing.

Methods:

A total of 106 eyes of 84 patients with Fuchs endothelial corneal dystrophy or bullous keratopathy (BK) were operated by a single experienced surgeon with DMEK with a 99% anterior chamber air bubble fill, recovered in an upright (seated) position, and then discharged without instructions to remain supine. Postoperatively, all eyes were evaluated for graft detachment through anterior segment optical coherence tomography at predetermined intervals (1 d, 1 wk, and 1 mo). Detachments were regarded as clinically significant if they subtended 30% of the total graft surface area or involved the visual axis.

Results:

Clinically significant graft detachments were observed in 23 of 106 eyes (22%) in the no-supine posturing cohort, including 22 of 85 eyes (26%) operated for Fuchs endothelial corneal dystrophy and 1 of 21 eyes (5%) operated for BK. Compared with a historical comparison group of eyes undergoing DMEK with 48 hours of postoperative supine posturing, the risk of graft detachment was not increased. In both cohorts, 6% of operated eyes required regrafting for either persistent detachment or primary graft failure. No additional intraoperative or postoperative complications were experienced.

Conclusions:

Particularly in eyes operated for BK, the supine posturing requirement after DMEK may be eliminated without increasing the absolute risk for clinically significant graft detachment.
Myeloid Sarcoma of the Temporal Bone: A Unique Cause of Hearing Loss, Otalgia, and Facial Nerve Weakness
Authors: Zheng Henry D. , Abdel-Aty Yassmeen , Taylor Cullen , Engholdt Jaime , Robetorye Ryan S. , Hoxworth Joseph M. , Marks Lisa , Weisskopf Peter A.
Published: February 2022

Objective:

To characterize a clinical triad of symptoms associated with myeloid sarcomas of the temporal bone via a review of all previously reported cases.

Methods:

Case report and Ovid MEDLINE database literature review.

Results:

A literature search revealed that a clinical triad of hearing loss, otalgia, and facial nerve weakness are commonly associated with this rare presentation of myeloid sarcoma in the temporal bone. 44% (18/41) of patients presented with all three symptoms, while 76% (31/41) presented with at least two. The presence of t(8;21) was reported in nine patients with myeloid sarcomas of the temporal bone.

Conclusions:

Although myeloid sarcomas are exceedingly rare, it is necessary to consider them as part of the differential diagnosis for patients who might present with middle ear and mastoid opacification on computed tomography (CT) scan, hearing loss, otalgia, and facial nerve palsy. Physicians should maintain a high degree of suspicion in patients with a history of acute myelogenous leukemia (AML), especially if previous cytogenetic analysis revealed a t(8;21).
Serum uric acid concentration is associated with hyperhomocysteinemia in hypertensive Chinese adults
Authors: Wang Wen , Wang Qian , Yang Nan
Published: February 2022

Purpose.

This study is to investigate the correlation between serum uric acid levels and hyperhomocysteinemia Chinese adult patients with hypertension.

Methods.

We enrolled 981 hypertensive patients, including unmedicated hypertensives, in our study. There were 453 patients with hyperhomocysteinemia (hyperhomocysteinemia hypertension group) and 528 without it (ordinary hypertension group). We collected histories of coronary heart disease, diabetes, and smoking and tested patients’ BMI, blood pressure, fasting serum uric acid, serum total cholesterol, triglycerides, low-density lipoprotein cholesterol, serum creatinine, and homocysteine. Subjects were stratified into four groups according to their serum uric acid quartiles: Q1 group, 249 cases (≤268 μmol/L); Q2 group, 245 cases (269–322 μmol/L); Q3 group, 244 cases (323–378 μmol/L); and Q4 group, 243 cases (≥379 μmol/L). We employ logistic regression analysis to investigate the relationship between serum uric acid levels and the risk of hyperhomocysteinemia in patients with hypertension.

Results.

We find that there were significant differences in gender distribution, serum uric acid, BMI, serum creatinine, total cholesterol, and diastolic blood pressure between the two groups (P < 0.05). The prevalence of hyperhomocysteinemia in groups Q1 through Q4 was 26.91% (67/249), 45.31% (111/245), 47.01% (117/244), and 65.02% (158/243), respectively, after adjusting for relevant factors, we find that the risk of hyperhomocysteinemia in the Q4 group was significantly higher than that in the Q1 group (odds ratio = 3.00, 95% confidence interval: 1.83–4.93).

Conclusion.

We find evidence that an elevated serum uric acid level is an independent indicator for hyperhomocysteinemia in patients with hypertension.
Nutritional impact of omega 3 fatty acids and metabolites in acute and chronic critical illness
Authors: Vanzant Erin , Loftus Tyler , Kamel Amir , Carmichael Ethan , Rosenthal Martin D.
Published: February 2022

Purpose of review

Lipids have been utilized historically as a calorie dense means to ensure delivery of essential fatty acids (FA). Since the development of mixed lipid emulsion and investigation of immunomodulatory formulas, there has been an awakening that not all lipids are created equal. This narrative review focuses on contemporary evidence in the utilization of lipids (namely omega 3 fatty acids) in both acute and chronic critical illness.

Recent findings

Though randomized control trials and meta-analyses provide little guidance regarding clinical practice for patients suffering from chronic critical illness, available literature suggests the potential to use lipid formulas to decrease the inflammatory cycle that drives catabolism. Additionally, this review will address the expanding evidence that specialized pro-resolving mediators (SPMs) may be the future of immunomodulating inflammation in acute and chronic critical illness and the persistent inflammation, immunosuppression, and catabolic syndrome (PICS).

Although societal guidelines, expert consensus, and literature support the use of omega 3 fatty acids in the acute critically ill population, more research is needed regarding omega 3 fatty acids for chronic critical illness and PICS.
Foreign body reaction mimicking local recurrence from polyactide adhesion barrier film after laparoscopic colorectal cancer surgery
Authors: Hsieh Tien-Chan , Hsu Chao-Wen
Published: February 2022

Polyactide (PLA) barrier is one of the most commonly used materials to prevent the formation of postoperative adhesion. Even though previous studies supported the anti-adhesion efficacy of PLA barrier, there have been limited reports focusing on the associated foreign body reaction. We sought to investigate the potential complication of PLA barrier placement that could lead to unnecessary intervention.

This is a retrospective study of colorectal cancer patients with laparoscopic surgery. Cases with stage IV unresectable disease, poor Eastern Cooperative Oncology Group Performance, death within 3 months after the surgery, and insufficient record were excluded. A total of 296 cases were identified in our study and 220 patients received PLA film placement. We compared the incidence of foreign body reaction between the patients with and without PLA film.

Among PLA film group, 16 cases had signs of local recurrence on the follow-up image studies. The subsequent operation found 10 patients had no cancerous lesions but only foreign-body-associated granulomas. The incidence of foreign body reaction mimicking local recurrence on image study was 4.5% with high false positive rate of 62.5% on positron emission tomography scan in patients with PLA film. There were only 2 cases without the antiadhesive barrier developed signs of recurrence during active surveillance. Both cases were later confirmed to have malignant peritoneal seeding.

The PLA film was associated with rare foreign body reaction that could interfere the accuracy of follow-up program and result in unnecessary surgical intervention. Hence, we recommend avoiding the use of the PLA barrier.
The rs1458038 variant near FGF5 is associated with poor response to calcium channel blockers among Filipinos
Authors: Punzalan Felix Eduardo R. , Cutiongco – de la Paz Eva Maria C. , Nevado Jose Jr. B. , Magno Jose Donato A. , Ona Deborah Ignacia D. , Aman Aimee Yvonne Criselle L. , Tiongson Marc Denver A. , Llanes Elmer Jasper B. , Reganit Paul Ferdinand M. , Tiongco Richard Henry P. , Santos Lourdes Ella G. , Aherrera Jaime Alfonso M. , Abrahan Lauro L. , Agustin Charlene F. , Bejarin Adrian John P. , Sy Rody G.
Published: February 2022

Genetic variation is known to affect response to calcium channel blockers (CCBs) among different populations. This study aimed to determine the genetic variations associated with poor response to this class of antihypertensive drugs among Filipinos.

One hundred eighty one hypertensive participants on CCBs therapy were included in an unmatched case-control study. Genomic deoxyribonucleic acid were extracted and genotyped for selected genetic variants. Regression analysis was used to determine the association of genetic and clinical variables with poor response to medication.

The variant rs1458038 near fibroblast growth factor 5 gene showed significant association with poor blood pressure-lowering response based on additive effect (CT genotype: adjusted OR 3.41, P = .001; TT genotype: adjusted OR 6.72, P < .001).

These findings suggest that blood pressure response to calcium channels blockers among Filipinos with hypertension is associated with gene variant rs1458038 near fibroblast growth factor 5 gene. Further studies are recommended to validate such relationship of the variant to the CCB response.
Cutaneous presentation of disseminated cytomegalovirus infection in a non-transplant patient with hematological malignancy
Authors: Yu Hung-Chuan , Liu Wang-Da , Kuo Po-Hsien , Lin Chien-Chin , Wu Un-In
Published: February 2022

Rationale:

Cytomegalovirus (CMV) disease is relatively uncommon in nontransplant hematological patients. Moreover, cutaneous manifestations of CMV diseases have scarcely been reported and are probably under-recognized.

Patient concerns:

We describe a patient with large B-cell lymphoma who developed a band-form, erythematous lesion over his left abdomen soon after the second course of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone chemotherapy.

Diagnoses:

The lesion was initially mistaken for bacterial cellulitis or herpes zoster and was histologically confirmed as cutaneous CMV infection. Subsequent work-up also detected CMV viremia and the presence of CMV meningoencephalitis.

Interventions:

The patient was treated with ganciclovir plus CMV immune globulin followed by foscarnet.

Outcomes:

Although the patient's cutaneous lesion resolved, his cognitive impairment did not recover, and he developed a fatal multi-organ failure 1 month later.

Lessons:

Cutaneous CMV disease can herald multisystem involvement and an unfavorable prognosis in immunocompromised hosts. It should be ruled out with biopsy in patients with hematological malignancy who have cutaneous lesions refractory to antibacterial therapy.
Efficacy and safety of sacubitril valsartan in treating heart failure with midrange ejection fraction after acute myocardial infarction in diabetic patients
Authors: Ye Fanhao , Li Hebo , Chen Xiaoshu , Wang Yi , Lin Wei , Chen Hao , Huang Shiwei , Han Sisi , Guan Fanlu , Huang Zhouqing
Published: February 2022

Objective to evaluate the clinical efficacy and safety of sacubitril valsartan in the treatment of heart failure (HF) with midrange ejection fraction after acute myocardial infarction (AMI) in diabetic patients. From January 2015 to July 2020, HF patients with diabetes mellitus complicated with AMI were retrospectively analyzed. According to the medication, they were divided into 2 groups, that is, sacubitril valsartan group (84 cases) and valsartan group (86 cases). Valsartan group took valsartan capsule (80 mg/capsule, Beijing Novartis Pharmaceutical Co., Ltd) 80 mg, qd, on the basis of routine treatment. On the basis of routine treatment, the sacubitril valsartan group took sacubitril valsartan sodium tablets (50 mg/tablet, Beijing Novartis Pharmaceutical Co., Ltd), the initial dose was 25 mg, bid, and gradually increased to the target dose according to the patient's blood pressure. After 12 months of treatment, the independent sample t test showed that the left ventricular end diastolic dimension in the sacubitril valsartan group was lower than that in the valsartan group [(47.26 ± 4.71) mm vs (50.05 ± 5.62) mm, P < .001]. The left ventricular ejection fraction in the sacubitril valsartan group was higher than that in the valsartan group [(54.76 ± 4.24)% vs (49.28 ± 3.74)%, P < .001]. χ2 inspection showed that the readmission rate in the sacubitril valsartan group was lower than that in the valsartan group (7.14% vs 18.60%, P < .05). Sacubitril valsartan has good safety and tolerability in patients with diabetes mellitus complicated with AMI who have HF with midrange ejection fraction. Compared with valsartan, sacubitril valsartan can improve the left ventricular function better and reduce the readmission rate due to HF in these patients.
A prediction model for 30-day deaths of cirrhotic patients in intensive care unit hospitalization
Authors: Hu Yuyuan , Chen Dongling , Li Qian , Yin Guichun , Zhang Xianjun , Wang Yachun
Published: February 2022

The aim of this study was to establish a prediction model for 30-day deaths of cirrhotic patients in intensive care unit.

A case-control study involving 1840 patients was conducted in the Medical Information Mart of the Intensive Care Database III version 1.4. The logistic regression with L1 regularization was used to screen out the variables. The 30-day in-hospital death was used as the dependent variable and the selected variables were used as the independent variable to build a random forest model. The performance of the model was validated by the internal validation.

The variables screened by logistic regression analysis were the age, heart rate, respiratory rate, systolic blood pressure, diastolic blood pressure, Oxygen saturation, white blood cells, platelets, red cell distribution width, glucose, blood urea nitrogen, bicarbonate, total bilirubin, hematocrit, alanine transaminase, aspartate transaminase, bilirubin, Simplified Acute Physiology Score II and Sequential Organ Failure Assessment. The areas under the curve of the random forest model based on these variables was 0.908, and the performance of this model were internally validated with an areas under the curve of 0.801. The random forest model displayed that Simplified Acute Physiology Score, Sequential Organ Failure Assessment, blood urea nitrogen, total bilirubin and bilirubin were more important predictors for the 30-day death of cirrhotic patients in intensive care unit.

A prediction model for death of cirrhotic patients was developed based on a random forest analysis, providing a tool to evaluate the patients with a high risk of 30-day in-hospital deaths to help clinician make preventive intervention to decrease the mortality.
Postoperative thoracogastric necrosis associated with thoracogastric–tracheal fistula of an endoscopic McKeown-type resection of esophageal carcinoma
Authors: Lu Yanhong , Ren Zixue
Published: February 2022

Introduction:

Postoperative thoracogastric necrosis (TGN) associated with thoracogastric-tracheal fistula (TGTF) of an endoscopic McKeown-type resection of esophageal carcinoma is rare and has a poor prognosis and high mortality. Few cases have been reported and successful treatment is rare. Surgery is the major treatment option.

Patient concerns:

A 71-year-old man was hospitalized in a local hospital for more than 2 months due to dysphagia. The patient was previously healthy and had no underlying diseases.

Diagnosis:

TGN associated with TGTF of an endoscopic McKeown-type resection of esophageal carcinoma.

Intervention:

Two-stage surgeries were performed.

Outcome:

The patient recovered well at the time of the follow-up examination on April 4, 2021 with an ECOG score of 0.

Conclusion:

Staging surgery can be an alternative treatment for TGN associated with TGTF of an endoscopic McKeown-type resection of esophageal carcinoma.