bluuebunny/crossref_metadata_2025 huggingface dataset:
4D flow MRI of type B dissection with later retrograde progression to type A dissection in Marfan: a case report
Authors: van Hout Max J P , Juffermans Joe F , Scholte Arthur J , Lamb Hildo J
Published: August 2021

Background 

Due to the malfunction of connective tissue, Marfan patients are at increased risk of aortic dissection. Uncomplicated acute type B dissection is usually managed with medical therapy. Retrograde progression or new type A dissection is a relatively rare but often fatal complication that occur most frequently in the first 6 months after acute type B dissection.

Case summary 

We present a 31-year-old male with Marfan syndrome and a recent uncomplicated type B dissection from the left subclavian to the right common iliac artery who underwent 4D flow magnetic resonance imaging (MRI). The dissection had a large proximal intimal tear just distal to the left subclavian artery (15 mm) and large false lumen (35 mm). Aortic blood flow just distal to the left subclavian artery (3.6 L/min) was split disproportionately into the true (0.8 L/min, 22%) and false lumen (2.8 L/min, 78%). 4D flow streamlines revealed vortical flow in the proximal false lumen. Increased wall shear stress was observed at the sinotubular junction (STJ), inner wall of the ascending aorta and around the subclavian artery. Two weeks after MRI, the patient presented with jaw pain. Computed tomography showed a type A dissection with an entry tear at the STJ for which an acute valve-sparing root, ascending and arch replacement was performed.

Discussion 

Better risk assessment of life-threatening complications in uncomplicated type B dissections could improve treatment strategies in these patients. Our case demonstrates that besides clinical and morphological parameters, flow derived parameters could aid in improved risk assessment for retrograde progression from uncomplicated type B dissection to acute type A dissection.
Detecting cardiomyopathies in pregnancy and the postpartum period with an electrocardiogram-based deep learning model
Authors: Adedinsewo Demilade A , Johnson Patrick W , Douglass Erika J , Attia Itzhak Zachi , Phillips Sabrina D , Goswami Rohan M , Yamani Mohamad H , Connolly Heidi M , Rose Carl H , Sharpe Emily E , Blauwet Lori , Lopez-Jimenez Francisco , Friedman Paul A , Carter Rickey E , Noseworthy Peter A
Published: August 2021

Aims

Cardiovascular disease is a major threat to maternal health, with cardiomyopathy being among the most common acquired cardiovascular diseases during pregnancy and the postpartum period. The aim of our study was to evaluate the effectiveness of an electrocardiogram (ECG)-based deep learning model in identifying cardiomyopathy during pregnancy and the postpartum period.

Methods and results

We used an ECG-based deep learning model to detect cardiomyopathy in a cohort of women who were pregnant or in the postpartum period seen at Mayo Clinic. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. We compared the diagnostic probabilities of the deep learning model with natriuretic peptides and a multivariable model consisting of demographic and clinical parameters. The study cohort included 1807 women; 7%, 10%, and 13% had left ventricular ejection fraction (LVEF) of 35% or less, <45%, and <50%, respectively. The ECG-based deep learning model identified cardiomyopathy with AUCs of 0.92 (LVEF ≤ 35%), 0.89 (LVEF < 45%), and 0.87 (LVEF < 50%). For LVEF of 35% or less, AUC was higher in Black (0.95) and Hispanic (0.98) women compared to White (0.91). Natriuretic peptides and the multivariable model had AUCs of 0.85 to 0.86 and 0.72, respectively.

Conclusions

An ECG-based deep learning model effectively identifies cardiomyopathy during pregnancy and the postpartum period and outperforms natriuretic peptides and traditional clinical parameters with the potential to become a powerful initial screening tool for cardiomyopathy in the obstetric care setting.
Microbe defines the efficacy of chemotherapeutic drug: a complete paradigm
Authors: Dalal P , Sharma D
Published: August 2021

The human body harbors a diverse microbiome that regulates host physiology and disease development. Several studies have also been reported where the human microbiome interferes with the efficacy of chemotherapeutics. Reports have also suggested the use of microbes in specific targeting and drug delivery. This review mainly focuses on the alteration in the efficacy of the drug by human microbiota. We have also discussed how the diversity in microbes can determine the therapeutic outcomes of a particular drug. The pathways involved in the alteration are also focused, with some highlights on microbes being used in cancer therapy.
High Levels of Psychological Resilience Are Associated With Decreased Anxiety in Inflammatory Bowel Disease
Authors: Philippou Alicia , Sehgal Priya , Ungaro Ryan C , Wang Kelly , Bagiella Emilia , Dubinsky Marla C , Keefer Laurie
Published: August 2021

Background

Anxiety and depression are comorbid disorders with IBD and are associated with poor outcomes. Resilience is an innate but modifiable trait that may improve the symptoms of psychological disorders. Increasing resilience may decrease the severity of these comorbid disorders, which may improve IBD outcomes. The aim of this study was to describe the association between resilience, anxiety, and depression in IBD patients.

Methods

We performed a cross-sectional study of IBD patients. Patients completed a questionnaire consisting of the Connor-Davidson Resilience Scale (CD-RISC), a measure of resilience, the Generalized Anxiety Disorder 7 (GAD-7), and the Patient Health Questionnaire-9. Primary outcome was severity of anxiety and depression in patients with high resilience. Multivariable linear regression analysis evaluated the association between severity of anxiety and depression and level of resilience.

Results

A sample of 288 patients was analyzed. Bivariable linear regression analysis showed a negative association between resilience and anxiety (Pearson rho = −0.47; P < .0001) and between resilience and depression (Pearson rho = −0.53; P < .0001). Multivariable linear regression indicated that high resilience is independently associated with lower anxiety and that for every 1-unit increase in CD-RISC, the GAD-7 score decreased by 0.04 units (P = .0003). Unlike anxiety, the association between resilience and depression did not remain statistically significant on multivariable analysis.

Conclusions

High resilience is independently associated with lower anxiety in IBD patients, and we report a quantifiable decrease in anxiety score severity for every point of increase in resilience score. These findings suggest that IBD patients with higher resilience may have better coping mechanisms that buffer against the development of anxiety.
Evolutionary Change in the Eastern Oyster,Crassostrea Virginica, Following Low Salinity Exposure
Authors: Griffiths Joanna S , Johnson Kevin M , Kelly Morgan W
Published: August 2021

Synopsis

The presence of standing genetic variation will play a role in determining a population's capacity to adapt to environmentally relevant stressors. In the Gulf of Mexico, extreme climatic events and anthropogenic changes to local hydrology will expose productive oyster breeding grounds to stressful low salinity conditions. We identified genetic variation for performance under low salinity (due to the combined effects of low salinity and genetic load) using a single-generation selection experiment on larvae from two populations of the eastern oyster, Crassostrea virginica. We used pool-sequencing to test for allele frequency differences at 152 salinity-associated genes for larval families pre- and post-low salinity exposure. Our results have implications for how evolutionary change occurs during early life history stages at environmentally relevant salinities. Consistent with observations of high genetic load observed in oysters, we demonstrate evidence for purging of deleterious alleles at the larval stage in C. virginica. In addition, we observe increases in allele frequencies at multiple loci, suggesting that natural selection for low salinity performance at the larval stage can act as a filter for genotypes found in adult populations.
T-Cell Immune Dysregulation and Mortality in Women With Human Immunodeficiency Virus
Authors: Peters Brandilyn A , Moon Jee-Young , Hanna David B , Kutsch Olaf , Fischl Margaret , Moran Caitlin A , Adimora Adaora A , Gange Stephen , Roan Nadia R , Michel Katherine G , Augenbraun Michael , Sharma Anjali , Landay Alan , Desai Seema , Kaplan Robert C
Published: August 2021

In women with HIV, higher activation and exhaustion of CD4+ T cells were associated with risk of non-HIV-related mortality during a median of 13.3 years of follow-up, independent of baseline demographic, behavioral, HIV-related, and cardiometabolic factors and longitudinal HIV disease progression.

Background

Dysregulation of adaptive immunity is a hallmark of human immunodeficiency virus (HIV) infection that persists on antiretroviral therapy (ART). Few long-term prospective studies have related adaptive immunity impairments to mortality in HIV, particularly in women.

Methods

Among 606 women with HIV in the Women’s Interagency HIV Study, peripheral blood mononuclear cells collected from 2002 to 2005 underwent multiparameter flow cytometry. Underlying cause of death was ascertained from the National Death Index up to 2018. We examined associations of CD4+ and CD8+ T-cell activation (%CD38+HLA-DR+), senescence (%CD57+CD28–), exhaustion (%PD-1+), and nonactivation/normal function (%CD57–CD28+) with natural-cause, HIV-related, and non-HIV-related mortality.

Results

At baseline, median participant age was 41, and 67% were on ART. Among 100 deaths during a median of 13.3 years follow-up, 90 were natural-cause (53 non-HIV-related, 37 HIV-related). Higher activation and exhaustion of CD4+ T cells were associated with risk of natural-cause and non-HIV-related mortality, adjusting for age, demographic, behavioral, HIV-related, and cardiometabolic factors at baseline. Additional adjustment for time-varying viral load and CD4+ T-cell count did not attenuate these associations. CD8+ T-cell markers were not associated with any outcomes adjusting for baseline factors.

Conclusions

Persistent CD4+ T-cell activation and exhaustion may contribute to excess long-term mortality risk in women with HIV, independent of HIV disease progression.
Benzo[a]pyrene stimulates miR-650 expression to promote the pathogenesis of fatty liver disease and hepatocellular carcinoma via SOCS3/JAK/STAT3 cascades
Authors: Ge Yang , Gu Pengfei , Wang Wenbo , Cao Liyuan , Zhang Lulu , Li Jingquan , Mu Wei , Wang Hui
Published: August 2021

Modern diets, which often feature high levels of fat and charcoal-grilled meat, contribute to the pathogenesis of obesity and non-alcoholic fatty liver disease (NAFLD), resulting in liver cancer progression. Benzo(a)pyrene (B[a]P) is a common environmental and foodborne pollutant found in smoke and fire-grilled foods, which can have an adverse effect on human health. Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer and the second leading cause of cancer-related deaths worldwide. The epidemiological studies suggest that both environmental risk factors and chronic liver injury including NAFL are important for HCC development, but the precise mechanisms linking eating habits to hepato-carcinogenesis remain unclear. In the present study, we demonstrated that various miRNAs in B[a]P-exposed tumor cells contribute to tumor metastasis, among which miR-650 could be the most potent inducer. Furthermore, we found that the suppressor of cytokine signaling 3 (SOCS3) is directly regulated by miR-650 and its suppression regulates the activation of the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) cascade. Our findings reveal a possible adverse outcome pathway of SOCS3/JAK/STAT3 regulation in B[a]P-induced HCC progress. These results provide a better understanding of the adverse effects of chronic exposure to B[a]P on human health.
Molecular Evidence Suggests That Wolbachia pipientis (Rickettsiales: Anaplasmataceae) is Widely Associated With South American Sand Flies (Diptera: Psychodidae)
Authors: Cruz Léo Nava Piorsky Dominici , Carvalho-Costa Luis Fernando , Rebêlo José Manuel Macário
Published: August 2021

Wolbachia pipientis (Hertig) is an endosymbiotic microorganism widespread among arthropods and other invertebrate hosts, and employed in strategies to reduce the incidence of arthropod-borne diseases. Here, we used a PCR-based approach for 16S RNA and wsp genes to investigate the prevalence, geographical distribution, and strains of Wolbachia in sand flies (Diptera: Psychodidae: Phlebotominae), the main vectors of the causative agents of leishmaniasis, from three biomes in Brazil: Amazon, Cerrado, and Caatinga. We found that: 1) Wolbachia DNA is present in most (66.7%) of the sampled sand fly species, including vectors of Leishmania spp. (Ross, Trypanosomatida: Trypanosomatidae), 2) the prevalence of Wolbachia DNA varies among species and populations, 3) some strains of Wolbachia may have wider geographical and host range in South America, and 4) two phylogenetic distinct wsp sequences might represent two novel strains for Wolbachia in South America sand flies. Those findings increase the basic knowledge about Wolbachia in South American sand flies and might foster further researches on its use to reduce the transmission of sand fly-borne parasites.
Experimental Study of the Mechanical Transmission of Rabbit Hemorrhagic Disease Virus (RHDV2/b) by Aedes albopictus (Diptera: Culicidae) and Phlebotomus papatasi (Diptera: Psychodidae)
Authors: Calvete C , Delacour S , Oropeza-Velasquez R V , Estrada R , Sarto M P , Iguacel L , Lucientes J , Calvo J H
Published: August 2021

Rabbit hemorrhagic disease (RHD) is caused by a lagovirus mainly affecting European rabbits (Oryctolagus cuniculus), although other European and North American lagomorph species are also susceptible to fatal infection by the new viral variant RHDV2/b. In the present work, direct mechanical transmission of the rabbit hemorrhagic disease virus (RHDV2/b variant) by the hematophagous Diptera Aedes albopictus (Skuse) (Diptera: Culicidae) and the sand fly Phlebotomus papatasi (Scopoli) (Diptera: Psychodidae) was tested. For each species, six and three laboratory rabbits were exposed to bites of dipterous females partially fed on RHDV2/b viral suspension 2 h and 24 h prior to exposure, respectively. The rabbits were then monitored for clinical changes and mortality for 35 d, and seroconversion was assessed by indirect ELISA. No rabbit died or showed clinical signs of disease, and seroconversion was recorded in two rabbits challenged with P. papatasi females fed the viral suspension 2 h prior to exposure. The number of RHDV2/b RNA copies/female was higher in Ae. albopictus than in P. papatasi but the decrease over time of RNA load in Ae. albopictus was greater than that in P. papatasi. The results of this study suggest the inability of Ae. albopictus to serve as a direct mechanical vector of RHDV2/b, but sand flies could play a role in the local transmission of RHD.
What Does #Freedom Look Like? Instagram and the Visual Imagination of Values
Authors: Trillò Tommaso , Scharlach Rebecca , Hallinan Blake , Kim Bumsoo , Mizoroki Saki , Frosh Paul , Shifman Limor
Published: August 2021

Instagram is the place for the visualization of everything, from travel and food to abstract concepts such as freedom. Over the past decade, the platform has introduced a bottom-up process where users co-produce image repertoires that shape the boundaries of the imaginable. Drawing on an epistemology of social constructionism, we ask which visual repertoires are associated with value-related terms on Instagram. We studied 20 widely used value hashtags, sampling the top 100 posts for each (N = 2,000). A combined qualitative–quantitative content analysis revealed that 19 of the 20 hashtags possess distinct visual footprints, typically reflecting an orientation toward the self and an emphasis on consumption. We conclude by discussing three implications of our findings: the role of images in the social construction of the meaning of values, the distinction between internalized and externalized value depictions, and aestheticized consumption as an organizing principle of Instagram’s mainstream.
Measuring time delays – II. Using observations of the unresolved flux and astrometry
Authors: Springer Ofer M , Ofek Eran O
Published: August 2021

Lensed quasars and supernovae can be used to study galaxies’ gravitational potential and measure cosmological parameters. The typical image separation of objects lensed by galaxies is of the order of 0.5 arcsec. Finding the ones with small separations, and measuring their time delays using ground-based observations is challenging. We suggest a new method to identify lensed quasars and simultaneously measure their time delays, using seeing-limited synoptic observations in which the lensed quasar images and the lensing galaxy are unresolved. We show that using the light curve of the combined flux, and the astrometric measurements of the centre-of-light position of the lensed images, the lensed nature of a quasar can be identified, and its time delay can be measured. We provide the analytic formalism to do so, taking into account the measurement errors and the fact that the power spectra of quasar light curves is red. We demonstrate our method on simulated data, while its implementation to real data will be presented in future papers. Our simulations suggest that, under reasonable assumptions, the new method has the potential to detect unresolved lensed quasars and measure their time delays, even when the image separation is about 0.2 arcsec, or the flux ratio between the faintest and brightest images is as low as 0.05. python and matlab implementations are provided. In a companion paper, we present a method for measuring the time delay using the combined flux observations. This method may be useful in cases in which the astrometric information is not relevant (e.g. reverberation mapping).
The effect of hairpin loop on the structure and gene expression activity of the long-loop G-quadruplex
Authors: Ravichandran Subramaniyam , Razzaq Maria , Parveen Nazia , Ghosh Ambarnil , Kim Kyeong Kyu
Published: August 2021

G-quadruplex (G4), a four-stranded DNA or RNA structure containing stacks of guanine tetrads, plays regulatory roles in many cellular functions. So far, conventional G4s containing loops of 1–7 nucleotides have been widely studied. Increasing experimental evidence suggests that unconventional G4s, such as G4s containing long loops (long-loop G4s), play a regulatory role in the genome by forming a stable structure. Other secondary structures such as hairpins in the loop might thus contribute to the stability of long-loop G4s. Therefore, investigation of the effect of the hairpin-loops on the structure and function of G4s is required. In this study, we performed a systematic biochemical investigation of model G4s containing long loops with various sizes and structures. We found that the long-loop G4s are less stable than conventional G4s, but their stability increased when the loop forms a hairpin (hairpin-G4). We also verified the biological significance of hairpin-G4s by showing that hairpin-G4s present in the genome also form stable G4s and regulate gene expression as confirmed by in cellulo reporter assays. This study contributes to expanding the scope and diversity of G4s, thus facilitating future studies on the role of G4s in the human genome.
Reconciling psychological and neuroscientific accounts of reduced motivation in aging
Authors: Soutschek Alexander , Bagaïni Alexandra , Hare Todd A , Tobler Philippe N
Published: August 2021

Motivation is a hallmark of healthy aging, but the motivation to engage in effortful behavior diminishes with increasing age. Most neurobiological accounts of altered motivation in older adults assume that these deficits are caused by a gradual decline in brain tissue, while some psychological theories posit a switch from gain orientation to loss avoidance in motivational goals. Here, we contribute to reconcile the psychological and neural perspectives by providing evidence that the frontopolar cortex (FPC), a brain region involved in cost–benefit weighting, increasingly underpins effort avoidance rather than engagement with age. Using anodal transcranial direct current stimulation together with effort–reward trade-offs, we find that the FPC’s function in effort-based decisions remains focused on cost–benefit calculations but appears to switch from reward-seeking to cost avoidance with increasing age. This is further evidenced by the exploratory, independent analysis of structural brain changes, showing that the relationship between the density of the frontopolar neural tissue and the willingness to exert effort differs in young vs older adults. Our results inform aging-related models of decision-making by providing preliminary evidence that, in addition to cortical thinning, changes in goal orientation need to be considered in order to understand alterations in decision-making over the life span.
Small-Scale Fungicide Delivery Equipment to Manage Early Blight in Three Types of Tomato
Authors: Barlow William , Pfeufer Emily
Published: August 2021

Management of early blight, one of the most common diseases of tomato, can be challenging for small- and large-scale growers alike, and robust disease resistance is not present in most commonly grown varieties. Comparisons of fungicide application equipment for early blight management have been completed for large-scale growers; however, comparisons have not been conducted of equipment suitable for small-scale plantings. In three trials, small-scale fungicide sprayer options (hand-pumped backpack, gasoline-powered mister-blower, and compressed CO2 backpack sprayer) were compared for effectiveness against early blight in determinate, indeterminate round-fruited, and indeterminate grape/cherry tomatoes. Results suggest that applying fungicides with a compressed CO2 sprayer most consistently managed early blight compared with other sprayer options tested in determinate tomatoes. Statistically significant differences in early blight severity by sprayer were not apparent for indeterminate grape/cherry tomato types and were variable for indeterminate round-fruited types. Determinate varieties consistently had the highest early blight severity among the three types of tomato evaluated. These results are influential to small-scale and beginning growers balancing the cost of fungicide application equipment with the type of tomato being grown.
Safety Profile for Microneedling: A Systematic Review
Authors: Chu Sherman , Foulad Delila P. , Atanaskova Mesinkovska Natasha
Published: August 2021

BACKGROUND

Microneedling is a minimally invasive procedure that stimulates collagen and elastin proliferation. It is used in the treatment of various skin pathologies, that is, scarring, photodamage, and hair loss; however, its safety profile has yet to be comprehensively reviewed.

OBJECTIVE

This review will discuss the reported side effects of microneedling in the current literature and delineate factors that increase the risk of complications.

MATERIALS AND METHODS

A literature search in August 2019 was conducted using the PubMed database to identify studies reporting adverse events (AEs) after microneedling therapy.

RESULTS

Eighty-five articles were included in this systematic review. The most common reported AEs are transient procedural events that are expected postprocedure lasting up to 7 days, such as transient erythema/edema and pain, postinflammatory hyperpigmentation (PIH), dry skin/exfoliation, lymphadenopathy, and irritant contact dermatitis. Persistent serious adverse effects included PIH, tram-track scarring, and granulomatous reactions. Factors that increase the risk of events are active infections, darker skin, and metal allergies.

CONCLUSION

Microneedling is a relatively safe therapy. Most reported AEs are minimal, resolving quickly and spontaneously. Caution should be taken in patients with active infection, darker skin types, metal allergies, and when used in conjunction with products not approved for intradermal use.
Depression, burnout, and professional outcomes among PAs
Authors: Blackstone Sarah R. , Johnson Aimee K. , Smith Noël E. , McCall Timothy C. , Simmons Whitney R. , Skelly Ashley W.
Published: August 2021

Objective:

This study examined the effect of depression and burnout on PA professional fulfillment and medical errors.

Methods:

Eight hundred eighty PAs completed an online survey containing the Professional Fulfillment Index, PHQ-2, GAD-7, and demographic questions. Two serial mediation models examined the relationship between depression, burnout, and professional outcomes.

Results:

Burnout fully mediated the relationship between depression and outcomes in both models and the present research indicates that burnout plays a stronger role in job satisfaction than symptoms of depression.

Conclusions:

Understanding the underpinnings of professional satisfaction may mitigate clinician turnover, which in turn may lead to cost savings for the organization, better resilience and mental health for clinicians, and potentially better patient outcomes.
Knockdown of Circular Ubiquitin-specific Peptidase 9 X-Linked Alleviates Oxidized Low-density Lipoprotein-induced Injuries of Human Umbilical Vein Endothelial Cells by Mediating the miR-148b-3p/KLF5 Signaling Pathway
Authors: Jiang Xiaowen , Chen Lei , Wu Hao , Chen Yuegao , Lu Weiqin , Lu Kaiping
Published: August 2021

There is evidence that the development of atherosclerosis (AS) involves the dysregulation of circular RNAs. This study aimed to investigate the role of circular ubiquitin-specific peptidase 9 X-linked (circUSP9X) in AS cell models. Human umbilical vein endothelial cells (HUVECs) treated with oxidized low-density lipoprotein (ox-LDL) were used as cell models of AS. The expression of circUSP9X, miR-148b-3p, and Kruppel-like factor 5 (KLF5) messenger RNA was measured using quantitative polymerase chain reaction. Cell viability was assessed by Cell Counting Kit-8 assay. Lactate dehydrogenase leakage, malonaldehyde content, and superoxide dismutase activity were investigated using matched commercial kits. Cell apoptosis was detected using flow cytometry assay. The protein levels of apoptosis-related markers and KLF5 were detected by western blot. The release of proinflammatory factors was monitored by enzyme-linked immunosorbent assay. The predicted relationship between miR-148b-3p and circUSP9X or KLF5 was confirmed by dual-luciferase reporter assay or RNA immunoprecipitation assay. CircUSP9X was highly expressed in ox-LDL–treated HUVECs. CircUSP9X knockdown inhibited ox-LDL–induced lactate dehydrogenase leakage, apoptosis, inflammation, and oxidative stress in HUVECs. CircUSP9X directly bound to miR-148b-3p, and KLF5 was a target of miR-148b-3p. CircUSP9X could regulate KLF5 expression by competitively targeting miR-148b-3p. Rescue experiments indicated that circUSP9X knockdown inhibited ox-LDL–induced HUVEC injuries by enriching miR-148b-3p, and miR-148b-3p restoration alleviated ox-LDL–induced HUVEC injuries by degrading KLF5. In conclusion, circUSP9X knockdown relieved ox-LDL–triggered HUVEC injuries during AS progression partly by mediating the miR-148b-3p/KLF5 network.
Nischarin Is Not the Functional I1 Imidazoline Receptor Involved in Blood Pressure Regulation
Authors: Arnoux Alizée , Aubertin Gaëlle , Da Silva Sylvia , Weiss Maud , Bousquet Pascal , Monassier Laurent , Niederhoffer Nathalie
Published: August 2021

Imidazoline receptor antisera selected/Nischarin was proposed several years ago as the functional entity for the I1 medullary receptors (I1Rs) targeted, together with α2-adrenoceptors, by the centrally acting antihypertensive drugs, such as clonidine. The objective of this study was to test this assumption using a pyrroline analog of clonidine, LNP599, which, unlike clonidine and related compounds, displays high selectivity toward I1Rs. Cardiovascular effects of LNP599 (3 mg/kg intravenous) were evaluated in anesthetized, artificially ventilated nischarin mutant rats expressing a truncated form of nischarin lacking the putative imidazoline binding site. LNP599 induced a rapid and pronounced fall in arterial blood pressure in wild-type animals (−42.7% ± 11.0% after 15 minutes), associated with a ≈30% heart rate reduction. Similar effects were obtained in homozygous and heterozygous nischarin mutant rats. The observation that the hypotensive response to I1R activation is not affected by the absence of the putative imidazoline binding site on nischarin strongly suggests that nischarin cannot be regarded as the functional I1R. Carbohydrate regulation was improved in nischarin mutant rats, further supporting the conclusion that nischarin and I1R are 2 distinct molecular entities.
The American Contact Dermatitis Society Core Allergen Series
Authors: Towery Laura E. , Marion Tyler , Montañez-Wiscovich Marjorie
Published: August 2021

Allergic contact dermatitis has been increasing in prevalence with the growing complexity of the ingredients in commercial products. The gold standard for the diagnosis of allergic contact dermatitis is patch testing. Patch testing allows for identification of relevant allergens that can then guide treatment with targeted avoidance. Although patch testing initially required clinicians to handpick suspected allergens, the development of a standard allergen panel in 1995 called the Thin-Layer Rapid Epicutaneous Test transformed the way patch testing is performed. In recent years, more comprehensive series have been developed, including the American Contact Dermatitis Society (ACDS) Core Allergen Series, which tests for 80 allergens rather than 36 allergens. The benefits of using the ACDS Series include (a) a greater likelihood of detecting relevant allergen(s), (b) a decreased need for repeat testing and subsequently fewer clinic appointments and less patient travel, and (c) an ability to update and modify the series of allergens based on consumer trends and patient data. Important/relevant allergens found in the ACDS Series but not the Thin-Layer Rapid Epicutaneous Test include many preservatives, adhesives, fragrances, and propylene glycol. We propose that patch testing with extended series of allergens be considered for first-line use when evaluating patients with suspected allergic contact dermatitis.
Lice Infestations in the Pediatric Population
Authors: Vassantachart Janna M. , Florentino Abigail , Admani Shehla
Published: August 2021

Lice cause a common pruritic condition known as pediculosis, which can cause significant psychosocial distress and embarrassment. The infestations can present differently in the pediatric population compared with the adult population, and certain infestations such as head lice are found more commonly in children. To avoid delayed diagnosis, healthcare providers should be knowledgeable of these differences. This article provides an overview of epidemiology and pathophysiology, clinical presentation and diagnosis, and management of lice infestations, specifically addressing the infant and children population.
A Crusted, Red–Violet, and Telangiectatic Cutaneous Nodule on the Forearm
Authors: Park Ariel , Serabyn Cynthia
Published: August 2021

Teledermatology is a term to describe the provision of dermatologic medical services through telecommunication technology. This is a teledermatology case of a firm, crusted, red–violet, and telangiectatic cutaneous nodule on the forearm.
Decision-Making in Sport During a Pandemic
Authors: Hamilton Bruce , Burt Peter , Anderson Lynley
Published: August 2021

Objective:

The COVID-19 pandemic has affected all elements of global society, and sport is not exempt. Many sporting events have been either postponed or canceled, and national sporting organizations have had to make highly complex decisions in the face of scientific uncertainty and risk. This article applies these lessons to the world of sport with the goal of assisting sporting organizations to make sound and reasoned decisions during a pandemic.

Data Sources:

A narrative approach using both academic literature sources and live examples from the authors' experience. We use Daniels and Sabin's accountability for reasonableness framework to facilitate decision-making in the face of such uncertainty.

Main Results:

Decision-making in the context of uncertainty has the potential to create conflict and disengagement from key stakeholders. Evidence from recent pandemics has illustrated that an ethical approach to decision-making results in reasoned decision-making and confers a legitimacy to decisions that ultimately supports engagement and satisfaction from stakeholders.

Conclusions:

The incorporation of ethical considerations into risk assessment and management when making complex decisions, which incorporate high levels of uncertainty, will assist sporting organizations have positive outcomes.
Long-term survival following radiofrequency ablation of lung metastases in an elderly patient with calcaneal osteosarcoma
Authors: Futani Hiroyuki , Takaki Haruyuki , Sawai Tatsuo , Taniguchi Junichi , Kako Yasukazu , Ide Yoshi-Hiro , Yamakado Koichiro , Tachibana Toshiya
Published: August 2021

Rationale:

Recently, the number of osteosarcomas has been increasing in elderly patients due to human longevity. Lung metastases are the primary cause of death from osteosarcomas. Complete resection of lung metastases can prolong the survival. However, complete resection in elderly patients is often difficult due to high risk of operative complications. Computed tomography (CT) guided radiofrequency ablation (RFA) is a minimally invasive technique to destroy tumor nodules using heat. In this report, we present the first case older than 65 years applying RFA for lung metastases due to osteosarcoma.

Patient concerns:

A 74-year-old male presented with 1-year history of heel pain. A conventional high-grade osteosarcoma in his calcaneus was diagnosed. Below-knee amputation was performed. However, lung metastases were found in both lungs 1 year after amputation. CT-guided lung RFA was chosen since surgical intervention for lung metastases was abandoned because of tumor multiplicity and medical comorbidities. A total of 18 lung metastases were treated by CT-guided RFA. The most frequent complication was pneumothoraxes in 4 of 8 (50%) procedures and chest tube drainage was required in 2 of these (2 of 8 (25%) procedures).

Diagnoses:

Six lung metastases of osteosaroma were found in both lungs at 1 year after surgery.

Interventions:

CT-guided lung RFA was performed. A total of 18 lung metastases were treated in 8 lung RF procedures.

Outcomes:

The patient has been alive with disease for 5.5 years after the initial surgery.

Lessons:

CT-guided lung RFA is effective for elderly patients with osteosarcoma lung metastases in spite of discouragement of lung metastasectomy due to multiplicity of metastases and medical-comorbidities.
The prognosis of cancer patients undergoing liposomal doxorubicin-based chemotherapy
Authors: Zhang Kai-Ping , Fang Xiang , Zhang Yin , Chao Min
Published: August 2021

Background:

It is well known that liposome-based delivery of cytotoxic chemotherapeutics has been proposed as a putative strategy to enhance drug tolerability and efficacy compared to the conventional chemotherapy. However, its potential effect on improving prognosis remains largely unknown. The current meta-analysis is to explore the prognosis of cancer patients undergoing liposomal doxorubicin-based chemotherapy.

Methods:

A detailed review of English and Chinese literature was conducted up to March 21, 2020. We evaluate its possible correlations using hazard ratios (HRs) with 95% confidence intervals (CIs). The pooled data were calculated by STATA software and Review Manager 5.3 software.

Results:

Consequently, 26 studies including 7943 patients were satisfied in current analysis. There were no significant differences between liposomal and conventional chemotherapy in OS (HR = 0.98, 95%CI: 0.93–1.04, P = .544) and PFS (HR = 1.00, 95%CI: 0.92–1.10, P = .945). Likewise, subgroup-analysis regarding country, cancer type, and sample sizes also showed the similar results of the 2 paired groups.

Conclusion:

Taken together, our finding has demonstrated that there was no association of undergoing liposomal doxorubicin-based chemotherapy with cancer prognosis. However, detailed and further studies are needed to confirm our conclusion.
Proposal of a simple grading system integrating cosmetic and tonometric aspects of prostaglandin-associated periorbitopathy
Authors: Tanito Masaki , Ishida Akiko , Ichioka Sho , Takayanagi Yuji , Tsutsui Aika , Manabe Kaoru , Shirakami Tomoki , Sugihara Kazunobu , Matsuo Masato
Published: August 2021

The distribution of prostaglandin-associated periorbitopathy (PAP) graded using the Shimane University PAP Grading System (SU-PAP) among glaucoma/ocular hypertension subjects using a topical FP or EP2 receptor agonist was reported. A 460 consecutive 460 Japanese subjects (211 men, 249 women; mean age ± standard deviation, 69.9 ± 14.5 years) who had used either a FP agonist (0.005% latanoprost, 0.0015% tafluprost, 0.004% travoprost, 0.03% bimatoprost, or fixed combinations of these) or EP2-agonist (0.002% omidenepag isopropyl) for more than 3 months in at least 1 eye were retrospectively enrolled. Age, sex, prostaglandin, intraocular pressure (IOP) measured by Goldmann applanation tonometry (IOPGAT) and iCare rebound tonometry (IOPRBT), difference between IOPGAT and IOPRBT (IOPGAT-RBT), PAP grade, and PAP grading items were compared among groups stratified by PAP grade or prostaglandins. Of the study patients, 114 (25%) had grade 0 (no PAP), 174 (38%) grade 1 (superficial cosmetic PAP), 141 (31%) grade 2 (deep cosmetic PAP), and 31 (7%) grade 3 (tonometric PAP). The IOPGAT was significantly higher in grade 3 (17.5 ± 5.4 mm Hg) than grades 0 (15.0 ± 5.1 mm Hg, P = .032) and 1 (14.5 ± 4.2 mm Hg, P = .008), and the IOPGAT-RBT was significantly higher in grade 3 (5.8 ± 3.2 mm Hg) than the other 3 grades (1.3–1.9 mm Hg, P < .001 for all comparisons); the IOPRBT was equivalent among the 4 grades. The PAP grade was significantly higher associated with travoprost (2.0 ± 0.8) and bimatoprost (2.0 ± 0.7) than latanoprost (1.0 ± 0.8, P < .001 for both comparisons) and tafluprost (1.0 ± 0.7, P < .001 for both comparisons), but significantly lower associated with omidenepag (0.0 ± 0.0, P < .001 for all comparisons) than the other 4 prostaglandins. Multivariate analyses showed older age (standard β = 0.11), travoprost (0.53, referenced by latanoprost) and bimatoprost (0.65) were associated with higher PAP grades, while tafluprost (−0.18) and omidenepag (−0.73) were associated with lower PAP grades. The PAP graded using SU-PAP reflects the degree of overestimation of the IOPGAT and different severities of PAP among the different prostaglandins. SU-PAP, the grade system constructed based on the underlining mechanisms of PAP, is a simple grading system for PAP that is feasible for use in a real-world clinical situation.
The cognitive dysfunction related to Alzheimer disease or cerebral small vessel disease
Authors: Liang Zhenhong , Wu Lijuan , Gong Shumei , Liu Xiaohong
Published: August 2021

Alzheimer disease (AD) and sporadic cerebral small vessel disease (CSVD) are common cognitive disorders. Both AD and CSVD have mental symptoms including chronic progressive cognitive impairment, dysfunction, and behavioral abnormalities. However, the differences on the cognitive dysfunction of AD and CSVD remain unclear. It is necessary to elucidate the cognitive dysfunction differences of AD and CSVD, and to identify the potential risk factors.

AD or sporadic CSVD patients treated in our hospital from December 1, 2018 to May 31, 2019 were included. And we selected healthy participants as controls. The mini-mental state examination and Montreal Cognitive Assessment Scale were used for neuropsychological assessment, and related medical information were collected and compared.

A total of 190 patients were included. The total mini-mental state examination scores in AD, CSVD group were significantly less than that of control group, there were significant differences in the domains of directional ability, attention and computing ability, delayed recall, and visual perception (all P < .05); the total Montreal Cognitive Assessment Scale scores in AD, CSVD group were significantly less than that of control group. There were significant differences in the domains of visual space and execution, immediate remember, attention and computing ability, language, delayed recall, and directional ability (all P < .05); diabetes was a risk factor both for AD (hazard ratio = 1.63, 95% confidence interval: 1.35–1.97) and CSVD (hazard ratio = 1.15, 95% confidence interval: 1.08–1.27).

The cognitive dysfunctions of AD are difference to that of CSVD patients, and diabetes is the risk factor both for AD and CSVD, future studies are needed to further identify the prevention and treatment of AD and CSVD.
Fasting blood glucose was linearly associated with colorectal cancer risk in the population without self-reported diabetes mellitus history
Authors: Wu Jingjing , He Huimin , Zhang Qi , Zhang Yan
Published: August 2021

Fasting plasma glucose level was linearly associated with colorectal cancer (CRC) risk. However, the dose–response relationship between fasting blood glucose (FBG) and CRC risk was still uncertain.

A total of 11,632 patients without self-reported diabetes mellitus and colorectal polyps’ history were identified in the Korean Multicenter Cancer Cohort (1993–2005). The nonlinear relationship was estimated through a restricted cubic spline regression, and a two-piece-wise Cox proportional hazards model was further performed to calculate the threshold effect. Multiple imputation was used to control the bias from missing data.

Overall, 1.1% (n = 132) of participants were diagnosed with CRC in the follow-up duration. With a median follow-up duration of 12.0 years, participants with FBG ≥126 mg/dL were associated with higher CRC risk (adjusted hazard ratio [HR], 1.67; 95% confidence interval [CI]: 1.01, 2.76). Landmark analyses limited to long-term survivors demonstrated increased CRC risk with FBG ≥ 126 mg/dL in all subsets (≥3years: HR,1.93 (95% CI: 1.13–3.29); ≥5years: HR, 2.04 (95% CI: 1.–3.63); ≥10years: HR, 2.50 (95% CI: 1.19–5.25)). With FBG smoothly increasing before, the latter increased dramatically after the turning point (P for nonlinearity = 0.283). When FBG was increasing per mmol/L, HR was 1.07(95% CI: 0.90, 1.29) for FBG < 126 mg/dL and 1.27 (95% CI: 1.06, 1.53) for FBG ≥ 126 mg/dL. Besides, HR was 1.09 (95% CI: 1.02, 1.16) for the CRC risk.

In the population without self-reported diabetes mellitus and colorectal polyps’ history. FBG was linearly associated with CRC risk, especially for FBG over 126 mg/dL.
Recanalization of XEN-45 gel stent occlusion with cortical material after phaco-XEN surgery using Nd: YAG laser treatment
Authors: Seo Je Hyun , Lim Su-Ho
Published: August 2021

Introduction:

The XEN Gel Stent (Allergan Inc., CA, USA) has been widely used in minimally invasive glaucoma surgery to lower intraocular pressure considering reasonable efficacy and safety profiles. However, the XEN gel stent could be occluded by fibrin, blood clots, or the iris due to its small lumen design for preventing postoperative hypotony. To date, only a few studies have assessed XEN occlusion after combined phacoemulsification with XEN gel implantation and how to manage this condition. We describe the first case report of XEN gel stent obstruction by cortical material, demonstrated by anterior segment optical coherence tomography (AS-OCT), which resolved effectively after low-energy neodymium-doped yttrium aluminum garnet (Nd: YAG) laser shock wave treatment.

Patient Information:

A 76-year-old Korean male patient underwent uncomplicated phaco-XEN-gel stent implantation and presented with low intraocular pressure (IOP) with a well-functioning filtering bleb during the first postoperative 4 days. On postoperative day 5, the XEN lumen was occluded by the cortical material, with an intraocular pressure elevation of 28 mm Hg. Slit-lamp examination revealed that cortical material was causing a block into the internal ostium of the XEN gel implant. AS-OCT examination also demonstrated the presence of hyper-reflective materials at the intraluminal portion and peritubular portion around the internal ostium of the XEN gel implant.

Diagnosis:

XEN gel stent occlusion with cortical material after Phaco-XEN surgery.

Interventions:

Low-energy Nd: YAG laser shock wave treatment.

Outcomes:

The IOP dropped from 28 mm Hg to 8 mm Hg immediately after treatment. Transient hypotony and a slightly shallow anterior chamber were noted over the 3 days after YAG laser treatment. The IOP continued to be well-controlled until 3 months later (range; 6 - 12 mm Hg).

Conclusions:

To the best of our knowledge, this is the first case report on the efficacy of Nd: YAG laser treatment for recanalization of XEN implant occluded by the cortex. Moreover, AS-OCT could provide additional clinical information for recanalization of the XEN gel stent.
Skeletal muscle metastasis from a gastrointestinal stromal tumor
Authors: Zhu Guangsheng , Sun Wenjia , Liu Yujun , Wang Huabin , Ye Shengwei
Published: August 2021

Rationale:

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Common sites for metastasis are the liver and peritoneum, whereas skeletal muscle metastases are rare.

Patient concerns:

A 59-year-old man with skeletal muscle metastasis was diagnosed during a period of adjuvant imatinib therapy following the recurrence of GIST of the small intestine.

Diagnosis:

The patient was diagnosed with skeletal muscle metastasis of GIST based on immunohistochemistry and molecular pathology analysis results.

Intervention:

Extensive resection of the left thigh tumor was performed. The patient underwent whole-exome sequencing of tissue examination. The results suggest that resistance to imatinib may have been developed, and the patient was therefore administered sunitinib instead.

Outcomes:

Complete remission was observed following sunitinib therapy.

Lessons:

In cases of skeletal muscle metastasis diagnosed during a period of adjuvant imatinib therapy following the recurrence of a GIST of the small intestine, whole exome sequencing may be used to discover more gene variations.
The predictive and prognostic effects of PD-L1 expression on TKI treatment and survival of EGFR-mutant NSCLC
Authors: Lan Bo , Wang Yongfang , Wu Jingni , Wang Kai , Wang Pingli
Published: August 2021

Whether programmed death-ligand 1 (PD-L1) expression could predict the outcome of tyrosine kinase inhibitor (TKI) treatment and prognosis of epidermal growth factor receptor (EGFR)-mutant nonsmall cell lung cancer (NSCLC) is remaining controversial.

Potential studies were search from PubMed, Embase, and Web of Science databases. Pooled odds ratio of objective response rate was used to describe the relationship between PD-L1 expression and primary resistance to EGFR-TKIs. Pooled hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS) were included to assess the effects of PD-L1 status on the outcome of EGFR-TKI treatment and survival of EGFR-mutant NSCLCs.

Eighteen eligible studies (1986 EGFR-mutant NSCLCs) were included in this meta-analysis. Positive PD-L1 expression correlated with lower objective response rate of EGFR-TKI treatment (odds ratio [95% confidence interval {CI}] = 0.52 [0.28–0.98], P = .043), while PFS (adjusted HR [95% CI] = 1.49 [0.96–1.89], P = .332) and OS (HR [95% CI] = 1.24 [0.70–2.20], P = .456) of EGFR-TKI treatment did not correlated with PD-L1 status. Furthermore, PD-L1 expression was not a predictive biomarker for the OS (HR [95% CI] = 1.43 [0.98–2.08], P = .062) in overall EGFR-mutant cohort.

Positive PD-L1 expression indicated a higher incidence of primary resistance, but did not correlate with the PFS or OS of EGFR-TKI therapy. In addition, PD-L1 expression was unlikely a predictive biomarker for prognosis of EGFR-mutant NSCLCs.