bluuebunny/crossref_metadata_2025 huggingface dataset:
Revised Exon Structure of l-DOPA Decarboxylase (DDC) Reveals Novel Splice Variants Associated with Colorectal Cancer Progression
Authors: Artemaki Pinelopi I. , Papatsirou Maria , Boti Michaela A. , Adamopoulos Panagiotis G. , Christodoulou Spyridon , Vassilacopoulou Dido , Scorilas Andreas , Kontos Christos K.
Published: November 2020

Colorectal cancer (CRC) is a highly heterogenous malignancy with an increased mortality rate. Aberrant splicing is a typical characteristic of CRC, and several studies support the prognostic value of particular transcripts in this malignancy. l-DOPA decarboxylase (DDC) and its derivative neurotransmitters play a multifaceted role in physiological and pathological states. Our recent data support the existence of 6 DDC novel exons. In this study, we investigated the existence of additional DDC novel exons and transcripts, and their potential value as biomarkers in CRC. Next-generation sequencing (NGS) in 55 human cell lines coupled with Sanger sequencing uncovered 3 additional DDC novel exons and 20 splice variants, 7 of which likely encode new protein isoforms. Eight of these transcripts were detected in CRC. An in-house qPCR assay was developed and performed in TNM II and III CRC samples for the quantification of transcripts bearing novel exons. Extensive biostatistical analysis uncovered the prognostic value of specific DDC novel exons for patients’ disease-free and overall survival. The revised DDC exon structure, the putative protein isoforms with distinct functions, and the prognostic value of novel exons highlight the pivotal role of DDC in CRC progression, indicating its potential utility as a molecular biomarker in CRC.
P2Y2 and P2X4 Receptors Mediate Ca2+ Mobilization in DH82 Canine Macrophage Cells
Authors: Sophocleous Reece Andrew , Miles Nicole Ashleigh , Ooi Lezanne , Sluyter Ronald
Published: November 2020

Purinergic receptors of the P2 subclass are commonly found in human and rodent macrophages where they can be activated by adenosine 5′-triphosphate (ATP) or uridine 5′-triphosphate (UTP) to mediate Ca2+ mobilization, resulting in downstream signalling to promote inflammation and pain. However, little is understood regarding these receptors in canine macrophages. To establish a macrophage model of canine P2 receptor signalling, the expression of these receptors in the DH82 canine macrophage cell line was determined by reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemistry. P2 receptor function in DH82 cells was pharmacologically characterised using nucleotide-induced measurements of Fura-2 AM-bound intracellular Ca2+. RT-PCR revealed predominant expression of P2X4 receptors, while immunocytochemistry confirmed predominant expression of P2Y2 receptors, with low levels of P2X4 receptor expression. ATP and UTP induced robust Ca2+ responses in the absence or presence of extracellular Ca2+. ATP-induced responses were only partially inhibited by the P2X4 receptor antagonists, 2′,3′-O-(2,4,6-trinitrophenyl)-ATP (TNP-ATP), paroxetine and 5-BDBD, but were strongly potentiated by ivermectin. UTP-induced responses were near completely inhibited by the P2Y2 receptor antagonists, suramin and AR-C118925. P2Y2 receptor-mediated Ca2+ mobilization was inhibited by U-73122 and 2-aminoethoxydiphenyl borate (2-APB), indicating P2Y2 receptor coupling to the phospholipase C and inositol triphosphate signal transduction pathway. Together this data demonstrates, for the first time, the expression of functional P2 receptors in DH82 canine macrophage cells and identifies a potential cell model for studying macrophage-mediated purinergic signalling in inflammation and pain in dogs.
A Stochastic Petri Net-Based Model of the Involvement of Interleukin 18 in Atherosclerosis
Authors: Formanowicz Dorota , Rybarczyk Agnieszka , Radom Marcin , Tanaś Krzysztof , Formanowicz Piotr
Published: November 2020

Interleukin 18 (IL-18) is a proinflammatory and proatherogenic cytokine with pleiotropic properties, which is involved in T and NK cell maturation and the synthesis of other inflammatory cytokines and cell adhesion molecules. It plays a significant role in orchestrating the cytokine cascade, accelerates atherosclerosis and influences plaque vulnerability. To investigate the influence of IL-18 cytokine on atherosclerosis development, a stochastic Petri net model was built and then analyzed. First, MCT-sets and t-clusters were generated, then knockout and simulation-based analysis was conducted. The application of systems approach that was used in this research enabled an in-depth analysis of the studied phenomenon. Our results gave us better insight into the studied phenomenon and allow revealing that activation of macrophages by the classical pathway and IL-18-MyD88 signaling axis is crucial for the modeled process.
Nox2 Upregulation and p38α MAPK Activation in Right Ventricular Hypertrophy of Rats Exposed to Long-Term Chronic Intermittent Hypobaric Hypoxia
Authors: Pena Eduardo , Siques Patricia , Brito Julio , Arribas Silvia M. , Böger Rainer , Hannemann Juliane , León-Velarde Fabiola , González M. Carmen , López M. Rosario , López de Pablo Ángel Luis
Published: November 2020

One of the consequences of high altitude (hypobaric hypoxia) exposure is the development of right ventricular hypertrophy (RVH). One particular type of exposure is long-term chronic intermittent hypobaric hypoxia (CIH); the molecular alterations in RVH in this particular condition are less known. Studies show an important role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex-induced oxidative stress and protein kinase activation in different models of cardiac hypertrophy. The aim was to determine the oxidative level, NADPH oxidase expression and MAPK activation in rats with RVH induced by CIH. Male Wistar rats were randomly subjected to CIH (2 days hypoxia/2 days normoxia; n = 10) and normoxia (NX; n = 10) for 30 days. Hypoxia was simulated with a hypobaric chamber. Measurements in the RV included the following: hypertrophy, Nox2, Nox4, p22phox, LOX-1 and HIF-1α expression, lipid peroxidation and H2O2 concentration, and p38α and Akt activation. All CIH rats developed RVH and showed an upregulation of LOX-1, Nox2 and p22phox and an increase in lipid peroxidation, HIF-1α stabilization and p38α activation. Rats with long-term CIH-induced RVH clearly showed Nox2, p22phox and LOX-1 upregulation and increased lipid peroxidation, HIF-1α stabilization and p38α activation. Therefore, these molecules may be considered new targets in CIH-induced RVH.
Tangeretin Ameliorates Glucose-Induced Podocyte Injury through Blocking Epithelial to Mesenchymal Transition Caused by Oxidative Stress and Hypoxia
Authors: Kang Min-Kyung , Kim Soo-Il , Oh Su Yeon , Na Woojin , Kang Young-Hee
Published: November 2020

Podocyte injury inevitably results in leakage of proteins from the glomerular filter and is vital in the pathogenesis of diabetic nephropathy (DN). The underlying mechanisms of podocyte injury facilitate finding of new therapeutic targets for DN treatment and prevention. Tangeretin is an O-polymethoxylated flavone present in citrus peels with anti-inflammatory and antioxidant properties. This study investigated the renoprotective effects of tangeretin on epithelial-to-mesenchymal transition-mediated podocyte injury and fibrosis through oxidative stress and hypoxia caused by hyperglycemia. Mouse podocytes were incubated in media containing 33 mM glucose in the absence and presence of 1–20 μM tangeretin for up to 6 days. The in vivo animal model employed db/db mice orally administrated with 10 mg/kg tangeretin for 8 weeks. Non-toxic tangeretin inhibited glucose-induced expression of the mesenchymal markers of N-cadherin and α-smooth muscle actin in podocytes. However, the reduced induction of the epithelial markers of E-cadherin and P-cadherin was restored by tangeretin in diabetic podocytes. Further, tangeretin enhanced the expression of the podocyte slit diaphragm proteins of nephrin and podocin down-regulated by glucose stimulation. The transmission electron microscopic images revealed that foot process effacement and loss of podocytes occurred in diabetic mouse glomeruli. However, oral administration of 10 mg/kg tangeretin reduced urine albumin excretion and improved foot process effacement of diabetic podocytes through inhibiting loss of slit junction and adherenes junction proteins. Glucose enhanced ROS production and HIF-1α induction in podocytes, leading to induction of oxidative stress and hypoxia. Similarly, in diabetic glomeruli reactive oxygen species (ROS) production and HIF-1α induction were observed. Furthermore, hypoxia-evoking cobalt chloride induced epithelial-to-mesenchymal transition (EMT) process and loss of slit diaphragm proteins and junction proteins in podocytes, which was inhibited by treating submicromolar tangeretin. Collectively, these results demonstrate that tangeretin inhibited podocyte injury and fibrosis through blocking podocyte EMT caused by glucose-induced oxidative stress and hypoxia.
Succinic Semialdehyde Dehydrogenase Deficiency: In Vitro and In Silico Characterization of a Novel Pathogenic Missense Variant and Analysis of the Mutational Spectrum of ALDH5A1
Authors: Brennenstuhl Heiko , Didiasova Miroslava , Assmann Birgit , Bertoldi Mariarita , Molla Gianluca , Jung-Klawitter Sabine , Kuseyri Hübschmann Oya , Schröter Julian , Opladen Thomas , Tikkanen Ritva
Published: November 2020

Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a rare, monogenic disorder affecting the degradation of the main inhibitory neurotransmitter γ-amino butyric acid (GABA). Pathogenic variants in the ALDH5A1 gene that cause an enzymatic dysfunction of succinic semialdehyde dehydrogenase (SSADH) lead to an accumulation of potentially toxic metabolites, including γ-hydroxybutyrate (GHB). Here, we present a patient with a severe phenotype of SSADHD caused by a novel genetic variant c.728T > C that leads to an exchange of leucine to proline at residue 243, located within the highly conserved nicotinamide adenine dinucleotide (NAD)+ binding domain of SSADH. Proline harbors a pyrrolidine within its side chain known for its conformational rigidity and disruption of protein secondary structures. We investigate the effect of this novel variant in vivo, in vitro, and in silico. We furthermore examine the mutational spectrum of all previously described disease-causing variants and computationally assess all biologically possible missense variants of ALDH5A1 to identify mutational hotspots.
Newborn Screening for Pompe Disease: Pennsylvania Experience
Authors: Ficicioglu Can , Ahrens-Nicklas Rebecca C. , Barch Joshua , Cuddapah Sanmati R. , DiBoscio Brenda S. , DiPerna James C. , Gordon Patricia L. , Henderson Nadene , Menello Caitlin , Luongo Nicole , Ortiz Damara , Xiao Rui
Published: November 2020

Pennsylvania started newborn screening for Pompe disease in February 2016. Between February 2016 and December 2019, 531,139 newborns were screened. Alpha-Glucosidase (GAA) enzyme activity is measured by flow-injection tandem mass spectrometry (FIA/MS/MS) and full sequencing of the GAA gene is performed as a second-tier test in all newborns with low GAA enzyme activity [<2.10 micromole/L/h]. A total of 115 newborns had low GAA enzyme activity and abnormal genetic testing and were referred to metabolic centers. Two newborns were diagnosed with Infantile Onset Pompe Disease (IOPD), and 31 newborns were confirmed to have Late Onset Pompe Disease (LOPD). The incidence of IOPD + LOPD was 1:16,095. A total of 30 patients were compound heterozygous for one pathogenic and one variant of unknown significance (VUS) mutation or two VUS mutations and were defined as suspected LOPD. The incidence of IOPD + LOPD + suspected LOPD was 1: 8431 in PA. We also found 35 carriers, 15 pseudodeficiency carriers, and 2 false positive newborns.
Neonatal Screening for MPS Disorders in Latin America: A Survey of Pilot Initiatives
Authors: Kubaski Francyne , Sousa Inês , Amorim Tatiana , Pereira Danilo , Trometer Joe , Souza Alexandre , Ranieri Enzo , Polo Giulia , Burlina Alberto , Brusius-Facchin Ana Carolina , Netto Alice Brinckmann Oliveira , Tomatsu Shunji , Giugliani Roberto
Published: November 2020

Newborn screening enables the diagnosis of treatable disorders at the early stages, and because of its countless benefits, conditions have been continuously added to screening panels, allowing early intervention, aiming for the prevention of irreversible manifestations and even premature death. Mucopolysaccharidoses (MPS) are lysosomal storage disorders than can benefit from an early diagnosis, and thus are being recommended for newborn screening. They are multisystemic progressive disorders, with treatment options already available for several MPS types. MPS I was the first MPS disorder enrolled in the newborn screening (NBS) panel in the USA and a few other countries, and other MPS types are expected to be added. Very few studies about NBS for MPS in Latin America have been published so far. In this review, we report the results of pilot studies performed in Mexico and Brazil using different methodologies: tandem mass spectrometry, molecular analysis, digital microfluidics, and fluorimetry. These experiences are important to report and discuss, as we expect to have several MPS types added to NBS panels shortly. This addition will enable timely diagnosis of MPS, avoiding the long diagnostic odyssey that is part of the current natural history of this group of diseases, and leading to a better outcome for the affected patients.
Evaluation of the Models for Forecasting Dengue in Brazil from 2000 to 2017: An Ecological Time-Series Study
Authors: Lima Marcos Venícius Malveira de , Laporta Gabriel Zorello
Published: November 2020

We aimed to evaluate the accuracy of deterministic and stochastic statistical models by means of a protocol developed in a free programming environment for monthly time-series analysis of the incidence of confirmed dengue cases in the states and federal district of Brazil from January 2000 to December 2017. This was an ecological time-series study conducted to evaluate and validate the accuracy of 10 statistical models for predicting the new cases of dengue. Official data on the monthly cases of dengue from January 2000 to December 2016 were used to train the statistical models, while those for the period January–December 2017 were used to test the predictive capacity of the models by considering three forecasting horizons (12, 6, and 3 months). Deterministic models proved to be reliable for predicting dengue in a 12-month forecasting horizon, while stochastic models were reliable for predicting the disease in a 3-month forecasting horizon. We were able to reliably employ models for predicting dengue in the states and federal district of Brazil. Hence, we strongly recommend incorporating these models in state health services for predicting dengue and for decision-making with regard to the advanced planning of interventions before the emergence of epidemics.
Interpopulational Variations of Odorant-Binding Protein Expression in the Black Cutworm Moth, Agrotis ipsilon
Authors: Picimbon Jean-François
Published: November 2020

A long-range migrant species of moth (Agrotis ipsilon) has served as a model to compare the expression profiles of antennal proteins between different continental populations. Our results showed that the American and French populations of the black cutworm moth, A. ipsilon, expressed the same odorant-binding proteins (OBPs), but apparently in different levels. Electrophoretic analysis of antennal protein profiles and reverse transcription polymerase chain reaction using RNA as a template showed significant differences between the two populations in the expression of antennal binding protein-X (ABPX) and general odorant-binding protein-2 (GOBP2). However, the two A. ipsilon populations showed no differences in RNA levels coding for pheromone binding proteins (PBPs), suggesting that the expression of generalist OBPs is population-specific and could be affected by specific odor and/or chemical changes in external environmental conditions. To support the role of ABPX and GOBP2 with expression, the role of ABPX and GOBP2 is discussed in regard to odor detection, memorization and/or degradation of toxic chemical insecticides.
Foraging Bumblebees Selectively Attend to Other Types of Bees Based on Their Reward-Predictive Value
Authors: Romero-González Jose E. , Royka Amanda L. , MaBouDi HaDi , Solvi Cwyn , Seppänen Janne-Tuomas , Loukola Olli J.
Published: November 2020

Using social information can be an efficient strategy for learning in a new environment while reducing the risks associated with trial-and-error learning. Whereas social information from conspecifics has long been assumed to be preferentially attended by animals, heterospecifics can also provide relevant information. Because different species may vary in their informative value, using heterospecific social information indiscriminately can be ineffective and even detrimental. Here, we evaluated how selective use of social information might arise at a proximate level in bumblebees (Bombus terrestris) as a result of experience with demonstrators differing in their visual appearance and in their informative value as reward predictors. Bumblebees were first trained to discriminate rewarding from unrewarding flowers based on which type of “heterospecific” (one of two differently painted model bees) was next to each flower. Subsequently, these bumblebees were exposed to a novel foraging context with two live painted bees. In this novel context, observer bumblebees showed significantly more social information-seeking behavior towards the type of bees that had predicted reward during training. Bumblebees were not attracted by paint-marked small wooden balls (moved via magnets) or paint-marked non-pollinating heterospecifics (woodlice; Porcellio laevis) in the novel context, indicating that bees did not simply respond to conditioned color cues nor to irrelevant social cues, but rather had a “search image” of what previously constituted a valuable, versus invaluable, information provider. The behavior of our bumblebees suggests that their use of social information is governed by learning, is selective, and extends beyond conspecifics.
Mediterranean Fruit Fly Ceratitis capitata (Diptera: Tephritidae) Eggs and Larvae Responses to a Low-Oxygen/High-Nitrogen Atmosphere
Authors: Al-Behadili Farhan J.M. , Agarwal Manjree , Xu Wei , Ren Yonglin
Published: November 2020

The Mediterranean fruit fly, Ceratitis capitata (Wiedemann) (Diptera: Tephritidae), is one of the most damaging horticultural insect pests. This study used a low-oxygen/high-nitrogen bioassay to control C. capitata. Two low-oxygen treatments were applied (0.5% O2 + 99.5 N2 and 5% O2 + 95% N2) to C. capitata eggs and 1st, 2nd and 3rd instar larvae from 0 to nine days on a carrot diet at 25 °C; 70—75% RH. The pupariation, adult emergence, and sex ratios of survived flies were examined. The results demonstrate that increased mortality of all tested life stages correlated with increased exposure times at both levels of low-oxygen treatments. Complete control of eggs was achieved after eight days and nine days for larvae using 0.5% O2 at 25 °C; 70–75% RH. The 3rd instar was the most tolerant stage, while the egg was the most susceptible stage to the low-oxygen environment. There were no significant differences in sex ratios between emerged adults after low-oxygen and control treatments. The present work demonstrates and confirms the mortalities of C. capitata caused by low-oxygen treatment, which may help develop new postharvest strategies to control this destructive fruit fly pest.
Maintaining Blood Glucose Levels in Range (70–150 mg/dL) is Difficult in COVID-19 Compared to Non-COVID-19 ICU Patients—A Retrospective Analysis
Authors: Kapoor Rajat , Timsina Lava R. , Gupta Nupur , Kaur Harleen , Vidger Arianna J. , Pollander Abby M. , Jacobi Judith , Khare Swapnil , Rahman Omar
Published: November 2020

Beta cell dysfunction is suggested in patients with COVID-19 infections. Poor glycemic control in ICU is associated with poor patient outcomes. This is a single center, retrospective analysis of 562 patients in an intensive care unit from 1 March to 30 April 2020. We review the time in range (70–150 mg/dL) spent by critically ill COVID-19 patients and non-COVID-19 patients, along with the daily insulin use. Ninety-three in the COVID-19 cohort and 469 in the non-COVID-19 cohort were compared for percentage of blood glucose TIR (70–150 mg/dL) and average daily insulin use. The COVID-19 cohort spent significantly less TIR (70–150 mg/dL) compared to the non-COVID-19 cohort (44.4% vs. 68.5%). Daily average insulin use in the COVID-19 cohort was higher (8.37 units versus 6.17 units). ICU COVID-19 patients spent less time in range (70–150 mg/dL) and required higher daily insulin dose. A higher requirement for ventilator and days on ventilator was associated with a lower TIR. Mortality was lower for COVID-19 patients who achieved a higher TIR.
Comparison of the Change in Diastolic Dysfunction after Transcatheter Atrial Septal Defect Closure between Asymptomatic Younger and Older Age Groups
Authors: Eun Lucy Youngmin , Park Han Ki , Choi Jae Young
Published: November 2020

Transcatheter device closure of a secundum atrial septal defect (ASD) is followed by a noticeable change in the left atrium (LA) and left ventricle (LV) over a long-term follow-up. This study aimed to assess the remodeling of the atrial and ventricular myocardium with respect to diastolic function in adult ASD patients. Around 38 asymptomatic patients (age: 48.6 ± 17.1 years, range: 23–69 years) diagnosed with ASD during routine health check-up and who underwent ASD device closure with the Amplatzer septal occluder were included in this retrospective study, and their medical records (containing echocardiographic data) were reviewed. The defect size was 21.77 + 6.79 mm, while the balloon measurement of the defect was 24.29 ± 6.64 mm. The patients were divided into two groups, namely, Group I (with 18 patients aged <50 years [mean: 33.06 ± 9.43 years] and Group II (with 20 patients aged ≥50 years [mean: 62.55 ± 7.54 years]). Comparison of echocardiographic data collected before closure and at a follow-up 2 years later revealed significant differences between pre-closure and post-closure states in the left ventricular end-diastolic dimension (40.76 ± 3.28 vs. 43.39 ± 3.52), left ventricular mass (99.64 ± 28.81 vs. 116.57 ± 32.03), and right ventricular pressure (36.88 ± 12.20 vs. 31.81 ± 11.11). Tissue Doppler measurements were significantly decreased 2 years after closure, while the post-closure E/E’ was higher than the pre-closure E/E’ (11.58 ± 4.80 vs. 8.79 + 3.19, p < 0.005). In both groups, mitral A and tissue Doppler E’, A’, and S’ values decreased post-closure, while the E/E’ was higher in Group II than in Group I at both pre-closure and long-term follow-up measurements (pre-closure: 9.60 ± 5.15 vs. 7.41 ± 1.42, p < 0.003; post-closure: 13.03 + 4.05 vs. 10.49 ± 3.95, p < 0.02). The LA size and LV function exhibited recognizable remodeling after transcatheter ASD closure. Because the LV preload elevation (i.e., E/E’) after ASD closure can be pronounced in older patients, caution should be provided more in older patients than in younger patients. Hence, it may be beneficial to close the ASD at an earlier age in adults even after a late diagnosis; a relatively younger age may be more suited for adaptation to the remodeling process to protect the myocardial function. Careful consideration should be given to the previous underloaded left heart after long-term closure.
What Opinions Do Tumor Reconstructive Surgeons Have about Sports Activity after Megaprosthetic Replacement in Hip and Knee? Results of the MoReSports Expert Opinion Online Survey
Authors: Hobusch Gerhard M. , Keusch Florian , Tsuchiya Hiroyuki , Joyce Michael , Windhager Reinhard
Published: November 2020

Sports activity has many benefits in cancer survivors. A key one is having sport activity contribute to the well-being of the individual. However, there are no guidelines about the intensity and kind of postoperative mobility workouts after hip or knee megaprosthetic treatment. Opinion research about sports after modular bone and joint replacement may provide an understanding of surgeons’ attitudes on sports activity after megaprostheses of the hip and knee joint. A web survey with members of three international professional organizations of orthopedic tumor reconstructive surgeons was conducted between September 2016 and January 2018. Members were invited via personalized emails by the European Musculoskeletal Oncology Society (EMSOS), the International Society of Limb Salvage (ISOLS), and the Musculoskeletal Tumor Society (MSTS). The questionnaire included 26 questions. A total of 149 surgeons started the survey, and 76 finished the entire survey (American Association for Public Opinion Research (AAPOR) second response rate (RR2) EMSOS: 12.3%; ISOLS: 21.9%; MSTS: n/a). More than half of the respondents encourage sarcoma survivors after megaprosthetic treatment to reach an activity level that would allow them to regularly participate in active sporting events of University of California, Los Angeles (UCLA) activity level 7 and higher. Orthopedic tumor reconstructive surgeons do fear a number of complications (periprosthetic fracture, allograft failure/fracture, loosening, prosthetic or bearing failure, and early polyethylene wear) due to sports activity after modular bone–joint replacement, but they actually witness fewer complications than they conceptually anticipated. According to the surgeons’ opinions, between four to seven types of sports after surgery could reasonably be recommended depending on the type of hip or knee procedures. This survey provides insights into opinions on what could be recommended, what could be allowed if surgeons and their patients agree on the potential negative outcome, and which sports should definitely not be allowed after hip and knee megaprostheses.
Particular Morphological Features in the Diagnosis of Pediatric Helicobacter pylori Gastritis: A Morphometry-Based Study
Authors: Domșa Ana-Maria Teodora , Gheban Dan , Lazăr Camelia , Pop Bogdan , Borzan Cristina Maria
Published: November 2020

Background: Current pediatric guidelines recommend the use of the Updated Sydney Classification for gastritis to assess histological changes caused by Helicobacter pylori (H. pylori) infection. The purpose of this study was to investigate the morphometric alterations of the antral mucosa in relation to pediatric H. pylori infection. Methods: A total of 65 cases were considered eligible. Apart from scoring the biopsies according to the recommendations, foveolar hyperplasia (FH) was assessed. The following measurements were performed on digital slides: total mucosal thickness, foveolar and glandular length, number of glandular cross sections per 40X field, glandular diameter, and distance between glands. Results: The thickness of the antral mucosa increased along with the bacterial density and the intensity of inflammation in H. pylori-infected children (p < 0.05). FH was significantly associated with the presence of H. pylori (p < 0.001) and also exhibited a greater length of the foveolar and glandular structures and an increased glandular diameter (p < 0.05), but without influencing the thickness of the mucosa. Conclusions: Our results reinforce the fact that FH is not only an important histologic characteristic of gastropathy, but is also a significant change observed in H. pylori infection in children and may be considered for reporting when evaluating pediatric gastric biopsies.
Who Will Continuously Depend on Compression to Control Persistent or Progressive Breast Cancer-Related Lymphedema Despite 2 Years of Conservative Care?
Authors: Jung Chul , Kim JaYoung , Seo Yu Jin , Song Kyeong Joo , Gelvosa Ma. Nessa , Kwon Jin Geun , Pak Changsik John , Suh Hyunsuk Peter , Hong Joon Pio , Kim Hwa Jung , Jeon Jae Yong
Published: November 2020

Background: When a patient with breast cancer-related lymphedema (BCRL) depends on continuous compression management, that is, when interstitial fluid accumulation is continuously ongoing, surgical treatment should be considered. Physiologic surgery is considered more effective for early-stage lymphedema. The purpose of this study was to identify predictors of patients with BCRL who will be compression-dependent despite 2 years of conservative care. Methods: This study included patients with BCRL who followed up for 2 years. Patients were classified into two groups (compression-dependent vs. compression-free). We identified the proportion of compression-dependent patients and predictors of compression dependence. Results: Among 208 patients, 125 (60.1%) were classified into the compression-dependent group. Compression dependence was higher in patients with direct radiotherapy to the lymph nodes (LNs), those with five or more LNs resections, and those with BCRL occurring at least 1 year after surgery. Conclusions: BCRL patients with direct radiotherapy to the LNs, extensive LN dissection, and delayed onset may be compression-dependent despite 2 years of conservative care. Initially moderate to severe BCRL and a history of cellulitis also seem to be strongly associated with compression dependence. Our results allow for the early prediction of compression-dependent patients who should be considered for physiologic surgery.
Characteristics, Management, and Outcomes of Acute Coronary Syndrome Patients with Cancer
Authors: Milazzo Valentina , Cosentino Nicola , Campodonico Jeness , Lucci Claudia , Cardinale Daniela , Cipolla Carlo M. , Marenzi Giancarlo
Published: November 2020

Patients with cancer are at increased risk of cardiovascular disease, with a reported prevalence of acute coronary syndrome (ACS) ranging from 3% to 17%. The increased risk of ACS in these patients seems to be due to the complex interaction of shared cardiovascular risk factors, cancer type and stage, and chemotherapeutic and radiotherapy regimens. The management of ACS in patients with cancer is a clinical challenge, particularly due to cancer’s unique pathophysiology, which makes it difficult to balance thrombotic and bleeding risks in this specific patient population. In addition, patients with cancer have largely been excluded from ACS trials. Hence, an evidence-based treatment for ACS in this group of patients is unknown and only a limited proportion of them is treated with antiplatelets or invasive revascularization, despite initial reports suggesting their beneficial prognostic effects in cancer patients. Finally, cancer patients experiencing ACS are also at higher risk of in-hospital and long-term mortality as compared to non-cancer patients. In this review, we will provide an overview on the available evidence of the relationship between ACS and cancer, in terms of clinical manifestations, possible underlying mechanisms, and therapeutic and prognostic implications.
Diabetic Retinopathy Environment-Wide Association Study (EWAS) in NHANES 2005–2008
Authors: Blighe Kevin , Gurudas Sarega , Lee Ying , Sivaprasad Sobha
Published: November 2020

Several circulating biomarkers are reported to be associated with diabetic retinopathy (DR). However, their relative contributions to DR compared to known risk factors, such as hyperglycaemia, hypertension, and hyperlipidaemia, remain unclear. In this data driven study, we used novel models to evaluate the associations of over 400 laboratory parameters with DR compared to the established risk factors. Methods: we performed an environment-wide association study (EWAS) of laboratory parameters available in National Health and Nutrition Examination Survey (NHANES) 2007–2008 in individuals with diabetes with DR as the outcome (test set). We employed independent variable (feature) selection approaches, including parallelised univariate regression modelling, Principal Component Analysis (PCA), penalised regression, and RandomForest™. These models were replicated in NHANES 2005–2006 (replication set). Our test and replication sets consisted of 1025 and 637 individuals with available DR status and laboratory data respectively. Glycohemoglobin (HbA1c) was the strongest risk factor for DR. Our PCA-based approach produced a model that incorporated 18 principal components (PCs) that had an Area under the Curve (AUC) 0.796 (95% CI 0.761–0.832), while penalised regression identified a 9-feature model with 78.51% accuracy and AUC 0.74 (95% CI 0.72–0.77). RandomForest™ identified a 31-feature model with 78.4% accuracy and AUC 0.71 (95% CI 0.65–0.77). On grouping the selected variables in our RandomForest™, hyperglycaemia alone achieved AUC 0.72 (95% CI 0.68–0.76). The AUC increased to 0.84 (95% CI 0.78–0.9) when the model also included hypertension, hypercholesterolemia, haematocrit, renal, and liver function tests.
Medical Nutritional Therapy for Patients with Chronic Kidney Disease not on Dialysis: The Low Protein Diet as a Medication
Authors: Cupisti Adamasco , Gallieni Maurizio , Avesani Carla Maria , D’Alessandro Claudia , Carrero Juan Jesus , Piccoli Giorgina Barbara
Published: November 2020

The 2020 Kidney Disease Outcome Quality Initiative (KDOQI) Clinical Practice Guideline for Nutrition in chronic kidney disease (CKD) recommends protein restriction to patients affected by CKD in stages 3 to 5 (not on dialysis), provided that they are metabolically stable, with the goal to delay kidney failure (graded as evidence level 1A) and improve quality of life (graded as evidence level 2C). Despite these strong statements, low protein diets (LPDs) are not prescribed by many nephrologists worldwide. In this review, we challenge the view of protein restriction as an “option” in the management of patients with CKD, and defend it as a core element of care. We argue that LPDs need to be tailored and patient-centered to ensure adherence, efficacy, and safety. Nephrologists, aligned with renal dietitians, may approach the implementation of LPDs similarly to a drug prescription, considering its indications, contra-indications, mechanism of action, dosages, unwanted side effects, and special warnings. Following this framework, we discuss herein the benefits and potential harms of LPDs as a cornerstone in CKD management.
Pilot Study on the Role of Circulating miRNAs for the Improvement of the Predictive Ability of the 2MACE Score in Patients with Atrial Fibrillation
Authors: Rivera-Caravaca José Miguel , Teruel-Montoya Raúl , Roldán Vanessa , Cifuentes-Riquelme Rosa , Crespo-Matas José Antonio , de los Reyes-García Ascensión María , Águila Sonia , Fernández-Pérez María Piedad , Reguilón-Gallego Laura , Zapata-Martínez Laura , García-Barberá Nuria , Vicente Vicente , Marín Francisco , Martínez Constantino , González-Conejero Rocío
Published: November 2020

Background. Atrial fibrillation (AF) increases the risk for stroke but also for non-stroke major adverse cardiovascular events (MACE). The 2MACE score was recently proposed to predict these events. Since the interest of microRNAs (miRNAs) in cardiovascular diseases is increasing, we aimed to investigate whether miRNA levels may improve the predictive performance of the 2MACE score. Methods. We included consecutive AF patients stable on vitamin K antagonist therapy. Blood samples were drawn at baseline and plasma expression of miRNAs was assessed. During a median of 7.6 (interquartile range (IQR) 5.4–8.0) years, the occurrence of any MACE (nonfatal myocardial infarction/cardiac revascularization and cardiovascular death) was recorded. Results. We conducted a miRNA expression analysis in plasma from 19 patients with and without cardiovascular events. The miRNAs selected (miR-22-3p, miR-107, and miR-146a-5p) were later measured in 166 patients (47% male, median age 77 (IQR 70–81) years) and all were associated with a higher risk of MACE. The addition of miR-107 and miR-146a-5p to the 2MACE score significantly increased the predictive performance (c-indexes: 0.759 vs. 0.694, p = 0.004), and the model with three miRNAs also improved the predictive performance compared to the original score (c-indexes: 0.762 vs. 0.694, p = 0.012). 2MACE models with the addition of miRNAs presented higher net benefit and potential clinical usefulness. Conclusions. Higher miR-22-3p andmiR-107 and lower miR-146a-5p levels were associated with a higher risk of MACE. The addition of these miRNAs to the 2MACE score significantly increased the predictive performance for MACE, which may aid to some extent in the decision-making process about risk stratification in AF.
Recurrence Pattern of Cervical Cancer Based on the Platinum Sensitivity Concept: A Multi-Institutional Study from the FRANCOGYN Group
Authors: de Foucher Tiphaine , Hennebert Cecile , Dabi Yohan , Ouldamer Lobna , Lavoué Vincent , Dion Ludivine , Canlorbe Geoffroy , Bolze Pierre Adrien , Golfier François , Akladios Cherif , Lecointre Lise , Kerbage Yohan , Collinet Pierre , Bricou Alexandre , Carcopino Xavier , Huchon Cyrille , Raimond Emilie , Graesslin Olivier , Owen Clémentine , Touboul Cyril , Ballester Marcos , Darai Emile , Bendifallah Sofiane
Published: November 2020

The standard of care for patients with advanced cervical cancer (ACC) includes platinum-based chemotherapy. The concept of platinum sensitivity is a major prognostic factor for patients with ovarian cancer. The aim of this study was to validate the applicability of the platinum sensitivity concept to ACC patients, and to estimate its prognostic interest in terms of overall survival (OS) and pattern of recurrence (location, timing). Data of women with histologically proven FIGO 2019 stages IB3–IV ACC, treated between May 2000 and November 2017 with platinum-based regimens, were retrospectively abstracted from 12 institutions from the FRANCOGYN Group. Respective 3-year OSs were 52% (95% CI: 40.8%–66.8%), 21.6% (95% CI: 12.6%–37.2%), and 14.6% (95% CI: 4.2%–50.2%), in case of recurrence <6 months, between 6 and 17 months, and ≥18 months (p < 0.001). Risk of metastatic or multisite recurrence was significantly higher in case of recurrence <6 months, and risk of local or isolated infradiaphragmatic nodal recurrence was significantly higher in case of recurrence >18 months (p < 0.001). In multivariate analysis, platinum sensitivity status was a strong prognostic factor for OS after recurrence, independent of histological grade, lympho-vascular space involvement, final lymph node status, and treatment. Platinum sensitivity status may help to classify patients in three prognostic subgroups for OS after recurrence, and appears to be a strong prognostic factor correlated to the pattern of recurrence.
Electrocardiographic Findings and Clinical Outcome in Patients with COVID-19 or Other Acute Infectious Respiratory Diseases
Authors: De Vita Antonio , Ravenna Salvatore Emanuele , Covino Marcello , Lanza Oreste , Franceschi Francesco , Crea Filippo , Lanza Gaetano Antonio
Published: November 2020

Background. Cardiac involvement in coronavirus SARS-CoV-2 infection (COVID-19) has been reported in a sizeable proportion of patients and associated with a negative outcome; furthermore, a pre-existing heart disease is associated with increased mortality in these patients. In this prospective single-center case-control study we investigated whether COVID-19 patients present different rates and clinical implications of an abnormal electrocardiogram (ECG) compared to patients with an acute infectious respiratory disease (AIRD) caused by other pathogens. Methods. We studied 556 consecutive patients admitted to the emergency department of our hospital with symptoms of AIRD; 324 were diagnosed to have COVID-19 and 232 other causes of AIRD (no-COVID-19 group). Standard 12-lead ECG performed on admission was assessed for various kinds of abnormalities, including ST segment/T wave changes, atrial fibrillation, ventricular arrhythmias, and intraventricular conduction disorders. Results. ECG abnormalities were found in 120 (37.0%) and 101 (43.5%) COVID-19 and no-COVID-19 groups, respectively (p = 0.13). No differences in ECG abnormalities were found between the 2 groups after adjustment for clinical and laboratory variables. During a follow-up of 45 ± 16 days, 51 deaths (15.7%) occurred in the COVID-19 and 30 (12.9%) in the no-COVID-19 groups (p = 0.39). ST segment depression ≥ 0.5 mm (p = 0.016), QRS duration (p = 0.016) and presence of any ECG abnormality (p = 0.027) were independently associated with mortality at multivariable Cox regression analysis. Conclusion. Among patients hospitalized because of AIRD, we found no significant differences in abnormal ECG findings between COVID-19 vs. no-COVID-19 patients. The ECG on admission was helpful to identify patients with increased risk of death in both groups of patients.
Classical McIndoe Technique Versus the McIndoe Technique with a Neovaginal PACIENA Prosthesis® and No Skin Graft
Authors: Navarro Victoria , Acién Maria Isabel , Acién Pedro
Published: November 2020

An observational, retrospective study was completed to compare the results of the PACIENA clinical trial (using the modified McIndoe technique) with a historical control group of nine patients who were operated on at San Juan University Hospital (1992–2015) using the classic technique. The PACIENA clinical trial included seven patients with vaginal agenesis who were operated on at two reference sites (May 2017–May 2018) using a neovaginal polylactic acid (PLA) prosthesis (PACIENA® prosthesis) and avoiding the use of a skin graft. The results illustrate a reduction in the length of surgery, 86.43 ± 4.75 min in the group with no skin graft compared to 155.56 ± 28.44 in the control group (p < 0.05); and reduction in the length of hospitalization time. Differences were also registered in the length of the neovagina, the average being 8.93 ± 1.42 cm for cases and 6.56 ± 1.13 cm for controls, with no differences in neovaginal epithelialization times or in the satisfaction of sexual relations occurring between groups. The modification of the classical McIndoe technique using the neovaginal PACIENA® prosthesis appears to be successful, obtaining good clinical results with shorter surgery and hospitalization times.
Relationship between Fall History and Self-Perceived Motor Fitness in Community-Dwelling People: A Cross-Sectional Study
Authors: Yokoi Katsushi , Miyai Nobuyuki , Utsumi Miyoko , Hattori Sonomi , Kurasawa Shigeki , Hayakawa Hiroko , Uematsu Yuji , Arita Mikio
Published: November 2020

History of falling is an important fall risk factor. If a relationship between fall history and self-perceived motor fitness could be established, then treating it as a correctable risk of re-fall due to falls may be possible. We conducted a cross-sectional study of the relationship between fall history and self-perceived motor fitness in daily life among 670 community-dwelling people (mean age 62.0 ± 9.6 years, 277 men and 393 women) who had participated in health examinations. They completed a self-administered questionnaire that asked about their history of single or multiple falls and included a 14-item motor fitness scale. The responses were analyzed using multivariate logistic regression analysis. The results showed that in both younger and older (<65 years) subjects, a history of single or multiple falls was associated with a negative response to “being able to put on socks, pants or a skirt while standing without support”. For subjects ≥65 years, an association was also observed with “shortness of breath when climbing stairs”. Self-perceived motor fitness related to fall history can easily be noticed by an individual and may help them become aware of fall-related factors earlier in everyday life.
Characterization of Non-Toxigenic Clostridioides difficile Strains Isolated from Preterm Neonates and In Vivo Study of Their Protective Effect
Authors: Couturier Jeanne , Franconeri Léa , Janoir Claire , Ferraris Laurent , Syed-Zaidi Rabab , Youssouf Anlyata , Gateau Cécile , Hoys Sandra , Aires Julio , Barbut Frédéric
Published: November 2020

In a previous monocentric study in preterm neonates (PN), we described a high Clostridioides difficile colonization rate (74%) with two uncommon non-toxigenic strains (NTCD) belonging to PCR-ribotype (RT) (CE)847 and (CE)032. To determine the extent of carriage of both NTCD in other spatio-temporal settings, strains isolated in PN stools from two multicenter cohorts were characterized by PCR-ribotyping, MLVA and MLST. We also evaluated the protective role of two NTCD from these RT against C. difficile infection in a hamster caecitis model. Animals were administered either each NTCD alone (n = 7), or followed by a 027 strain (n = 9). A control group received only the 027 strain (n = 8). Clinical activity and colonization by C. difficile in stools were monitored daily until death or sacrifice at D20. We isolated 18 RT(CE)032 (ST-83) strains and 2 RT(CE)847 (ST-26) strains among 247 PN from both cohorts. Within each RT, strains were genetically related. The survival rate was significantly increased when animals received a RT(CE)847 or (CE)032 strain before the 027 strain (4/9 deaths, p = 0.029; 1/9 death, p = 0.0004, respectively). We describe two predominant uncommon NTCD strains, in a PN population from different healthcare facilities. Both NTCD provide a potential protection against C. difficile infection.
Prediction of Recurrent Emergency Department Visits among Patients with Crohn’s Disease: A Retrospective Study
Authors: Mahajna Hussein , Barash Yiftach , Ungar Bella , Soffer Shelly , Albshesh Ahmad , Levartovsky Asaf , Ben-Horin Shomron , Klang Eyal , Kopylov Uri
Published: November 2020

Patients with Crohn’s disease (CD) are frequently subject to symptoms causing them to seek medical care in emergency departments (ED). Recurrent ED visits are frequent after initial discharge. We aimed to identify the characteristics of patients with Crohn’s who tend to have recurrent visits to the ED. We created an electronic data repository of all patients with inflammatory bowel diseases who visited the ED in our tertiary medical center during the period 2012–2018. For this study, we retrieved consecutive Crohn’s patients who presented with CD-related symptoms to the ED and were eventually discharged. Patients who returned to the ED in 7 and 30 days were compared with those who did not. Overall, 2299 patients visited our ED with complaints related to Crohn’s disease exacerbation or complication. A total of 1259 (60% of the adult patients) were admitted for hospitalization. Of the 632 (33%) who were discharged from the ED, 53 (8.4%) and 110 (17.4%) re-visited the ED, in 7 and 30 days from discharge, respectively. In multivariable analysis, tachycardia (odds ratio (OR) = 2.19, 95% confidence interval (CI): 1.11–4.33, p value = 0.02), elevated alkaline phosphatase (OR = 2.09, 95% CI: 1.07–4.07, p value = 0.02), and hyponatremia (OR = 2.52, 95% CI: 1.24–5.10, p value = 0.01) were associated with revisiting the ED within 7 days. Tachycardia (OR 2.88 (95% CI 1.33–6.2)), anemia (OR 2.44 (95% CI 1.24–4.8)), and elevated alkaline phosphatase (OR 2.68 (95% CI 1.25–5.78)) were independently associated with ED returns in 30 days. Knowing these risk factors may assist in minimizing the burden of recurrent ED visits among patients with CD.