bluuebunny/crossref_metadata_2025 huggingface dataset:
Amylase Alpha 1 Gene (AMY1) Copy Number Variation and Dental Caries Experience: A Pilot Study among Adults in Lithuania
Authors: Stangvaltaite-Mouhat Lina , Pūrienė Alina , Aleksejūnienė Jolanta , Stankeviciene Indre , Tommeras Berit , Al-Haroni Mohammed
Published: March 2021

Introduction: Genetic biomarkers have the potential to be used in personalised dentistry for improved prevention and decision-making in caries management. The amylase alpha 1 gene (AMY1) encodes salivary α-amylase and may be one such biomarker. We examined the association between AMY1 copy number variation (CNV) and dental caries experience in adults. Materials and Methods: A stratified random sample of 193 participants from the Lithuanian National Oral Health Survey (LNOHS) agreed to provide saliva samples and were included in this analysis (age 35–44 years; participation rate 43%). Information on socio-demographic and behavioural characteristics was taken from the LNHOS, which used the self-administered World Health Organisation (WHO) questionnaire. Data on fluoride levels in drinking water at the recruitment areas was recorded based on information provided by water suppliers. Dental caries experience was recorded at a surface level (smooth-surface and occlusal-surface decayed, missing, filled surfaces [D3MFS] score) by one trained and calibrated examiner using WHO criteria, and subsequently dichotomised for the statistical analyses. DNA extracted from saliva samples was used to investigate AMY1 CNV using the QX200 droplet digital PCR system. Bivariate and multivariable statistical analyses were employed. Results: When compared to participants with an AMY1 copy number (CN) of 2–3, higher odds of smooth-surface D3MFS >14 was observed for participants with a CN of 4–5 (OR 13.3, 95% CI 2.1–86.3), 6–9 (OR 7.0, 95% CI 1.4–34.1), and 10–16 (OR 5.8, 95% CI 1.2–32.2). Female sex was independently associated with a smooth-surface D3MFS >14 (OR 5.7, 95% CI 1.9–17.2). Conclusions: Our study demonstrated an association between AMY1 CNV and high smooth-surface caries experience. Studies with larger sample sizes are needed to validate this association.
Neonatal Hypoglycaemia: A Never-Ending Story?
Authors: Vain Nestor E. , Chiarelli Florencia
Published: March 2021

Neonatal hypoglycaemia is a common metabolic disorder presenting in the first days of life and one potentially preventable cause of brain injury. However, a universal approach to diagnosis and management is still lacking. The rapid decrease in blood glucose (BG) after birth triggers homeostatic mechanisms. Most episodes of hypoglycaemia are asymptomatic, and symptoms, when they occur, are nonspecific. Therefore, neonatologists are presented with the challenge of identifying infants at risk who might benefit from a rapid and effective therapy while sparing others unnecessary sampling and overtreatment. There is much controversy regarding the definition of hypoglycaemia, and one level does not fit all infants since postnatal age and clinical situations trigger different accepted thresholds for therapy. The concentration and duration of BG which cause neurological damage are unclear. Recognizing which newborn infants are at risk of hypoglycaemia and establishing protocols for treatment are essential to avoid possible deleterious effects on neurodevelopment. Early breastfeeding may reduce the risk of hypoglycaemia, but in some cases, the amount of breast milk available immediately after birth is insufficient or non-existent. In these situations, other therapeutic alternatives such as oral dextrose gel may lower the risk for NICU admissions. Current guidelines continue to be based on expert opinion and weak evidence. However, malpractice litigation related to neurodevelopmental disorders is frequent in children who suffered hypoglycaemia in the neonatal period even if they had other important factors contributing to the poor outcome. This review is aimed to help the practicing paediatricians and neonatologists to comprehend neonatal hypoglycaemia from physiology to therapy, hoping it will result in a rational decision-making process in an area not sufficiently supported by evidence.
Tofacitinib: An Option for Acute Severe Ulcerative Colitis?
Authors: Santos Sara , Gamelas Verónica , Saraiva Rita , Simões Guilherme , Saiote Joana , Ramos Jaime
Published: March 2021

Tofacitinib has emerged as a new option for ulcerative colitis. Its rapid absorption, metabolism, and clinical improvement make it an interesting option for rescue therapy in acute severe ulcerative colitis (ASUC), a situation with limited therapeutic options in patients with a long-term disease course and multiple drug failure. The management of ASUC in this setting becomes challenging, underlying the need for new drugs and data on their efficacy and safety. We describe 2 cases of acute episodes in which tofacitinib was used as a rescue therapy.
A Rare Presentation of a Solid Pseudopapillary Neoplasm of the Pancreas
Authors: Silva Raphael José da , Oliveira Isaac Nilton Fernandes , Ribeiro Tarsila Campanha da Rocha , Chebli Liliana Andrade , Pace Fábio Heleno de Lima , Chebli Julio Maria Fonseca
Published: March 2021

Solid pseudopapillary neoplasms (SPN) are rare and represent a minority of all pancreatic cystic tumors. Symptoms, if present, are generally nonspecific and upper gastrointestinal bleeding is extremely uncommon as an initial presentation. A 31-year-old woman with no prior medical history presented with a 3-week period of epigastric pain, which she reported as persistent, exacerbated by eating, and associated with progressive asthenia, fatigue, and exertional dyspnea. One month prior, she had had experienced 2 episodes of melena. Upon physical examination her skin was pale, with no other changes. Through diagnostic investigation, an esophagogastroduodenoscopy showed a giant ulcer in the duodenal bulb and a suspect fistulous orifice localized on the posterior wall of the duodenal bulb. In addition, a bulge on the duodenal bulb, suggestive of an extrinsic compression, was noticed. An abdominal computed tomography scan and magnetic resonance imaging showed a mixed solid and cystic lesion in the head of the pancreas in direct proximity to the duodenum, which contained an image compatible with a fistula. The patient successfully underwent pancreaticoduodenectomy. The histopathology, including microscopic analysis and immunohistochemistry, was consistent with an SPN of the pancreas. This case emphasizes that the evaluation of patients presenting with upper gastrointestinal bleeding due to a giant duodenal ulcer and an extrinsic mass effect noted on the duodenum should include cross-sectional images of the abdomen. In this case, the finding of a large well-encapsulated pancreatic solid and cystic mass on abdominal images was suggestive of a pancreatic neoplasm diagnosis, including an SPN.
First Experiences with Alpelisib in Clinical Routine: Case Reports from a German Breast Center
Authors: Hester Anna , Henze Franziska , Travi Christiane , Harbeck Nadia , Wuerstlein Rachel
Published: March 2021

Introduction: The phosphatidylinositol-3-kinase (PI3K) inhibitor alpelisib is the only approved agent for treating ­PIK3CA-mutated, hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC). Trials have reported hyperglycemia, diarrhea, and rash as the main grade 3 side effects. Methods: In a managed access program (ClinicalTrials.gov ID: NCT03706573; start: 06/2019), 8 HR+ HER2– ABC patients with a median 4.5 prior therapy lines were treated with alpelisib at the Breast Center of the Ludwig-Maximilian University (LMU) Hospital, Munich, based on the results of a new-generation sequencing (NGS) panel and PIK3CA mutation analysis by the Molecular Tumor Board of the Comprehensive Cancer Center, Munich. Results: Median therapy duration was 3.42 months for patients who discontinued and 3.95 months for those still on alpelisib (4 pts). Five had hyperglycemia (1 with grade 3) with fasting glucose levels of up to 450 mg/dL that required hospitalization and insulin therapy. Two experienced rash (grades 1 and 3) and 2 reported grade 3 diarrhea. Supportive therapy as well as interruption and/or dose reduction were necessary to control treatment-associated side effects. Conclusion: Patient education and a well-trained, interdisciplinary team including diabetologists, from the initiation of alpelisib treatment onwards, are essential to safely treat ABC patients with this new drug and to maintain their quality of life and ensure their survival.
Bortezomib Treatment for Refractory PLA2R-Positive Membranous Nephropathy
Authors: Geara Abdallah S. , Bhoj Vijay , Hogan Jonathan J.
Published: March 2021

Introduction: B-cell depletion has been shown to be an effective strategy for the majority of patients with membranous nephropathy (MN), and in PLA2R-positive MN, immunologic remission (improvement or elimination of measurable serum anti-PLA2R antibodies) precedes renal remission. Yet, cases exist of patients who do not achieve immunologic remission despite achieving peripheral B-cell depletion. This has led to the hypothesis that some patients have plasma cells that are responsible for producing anti-PLA2R antibodies. Case Presentation: A 66-year-old man with a past medical history of hypertension, hyperlipidemia, and cerebrovascular disease presented with nephrotic syndrome and was diagnosed with PLA2R-positive MN on kidney biopsy. He was refractory to multiple therapies including tacrolimus, and was resistant to rituximab despite having achieved B-cell depletion. He also did not enter into remission with plasmapharesis and cyclophosphamide. He then achieved immediate immunologic remission after treatment with the proteasome inhibitor bortezomib, which is used as first-line therapy for multiple myeloma. Discussion/Conclusion: This case suggests that considering the source of PLA2R antibody production could lead to individualized and targeted therapies for MN.
Fluoride Binding to Streptococcus mutans Pellets Rich in Extracellular Polysaccharides
Authors: Pagotto Leonardo Libardi , Spinola Manuela da Silva , Nóbrega Diego Figueiredo , Cury Jaime Aparecido , Tenuta Livia Maria Andaló
Published: March 2021

Extracellular polysaccharides (EPS), mainly the insoluble ones, increase the cariogenicity of dental biofilm, but whether they interfere with the binding and retention of fluoride is unknown. EPS-rich (EPS+) and EPS-poor (EPS–) pellets of Streptococcus mutans were formed and treated with increasing fluoride concentrations (0, 0.1, 1, or 10 mM). A concentration-dependent fluoride binding was observed in both EPS– and EPS+ pellets, but the presence of EPS did not affect the retention of fluoride in the pellets. In conclusion, the data suggest that a matrix of dental biofilm rich in EPS does not affect fluoride retention in the biofilm.
SARS-CoV-2 Lineages and Sub-Lineages Circulating Worldwide: A Dynamic Overview
Authors: Cella Eleonora , Benedetti Francesca , Fabris Silvia , Borsetti Alessandra , Pezzuto Aldo , Ciotti Marco , Pascarella Stefano , Ceccarelli Giancarlo , Zella Davide , Ciccozzi Massimo , Giovanetti Marta
Published: March 2021

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in Wuhan, China, in early December 2019 has rapidly widespread worldwide, becoming one of the major global public health issues of the last centuries. Key Messages: Over the course of the pandemic, due to the advanced whole-genome sequencing technologies, an unprecedented amount of genomes have been generated, providing invaluable insights into the ongoing evolution and epidemiology of the virus during the pandemic. Therefore, this large amount of data played an important role in the SARS-CoV-2 mitigation and control strategies. Key Messages: The active monitoring and characterization of the SARS-CoV-2 lineages circulating worldwide is useful for a more specific diagnosis, better care, and timely treatment. In this review, a concise characterization of all the lineages and sub-lineages circulating and co-circulating across the world has been presented in order to determine the magnitude of the SARS-CoV-2 threat and to better understand the virus genetic diversity and its dispersion dynamics.
A Putative Adverse Outcome Pathway Network for Disrupted Female Pubertal Onset to Improve Testing and Regulation of Endocrine Disrupting Chemicals
Authors: Franssen Delphine , Svingen Terje , Lopez Rodriguez David , Van Duursen Majorie , Boberg Julie , Parent Anne-Simone
Published: March 2021

The average age for pubertal onset in girls has declined over recent decades. Epidemiological studies in humans and experimental studies in animals suggest a causal role for endocrine disrupting chemicals (EDCs) that are present in our environment. Of concern, current testing and screening regimens are inadequate in identifying EDCs that may affect pubertal maturation, not least because they do not consider early-life exposure. Also, the causal relationship between EDC exposure and pubertal timing is still a matter of debate. To address this issue, we have used current knowledge to elaborate a network of putative adverse outcome pathways (pAOPs) to identify how chemicals can affect pubertal onset. By using the AOP framework, we highlight current gaps in mechanistic understanding that need to be addressed and simultaneously point towards events causative of pubertal disturbance that could be exploited for alternative test methods. We propose 6 pAOPs that could explain the disruption of pubertal timing by interfering with the central hypothalamic trigger of puberty, GnRH neurons, and by so doing highlight specific modes of action that could be targeted for alternative test method development.
Evaluation of Diarrhea in Patients with COVID-19
Authors: Comoglu Şenol , Öztürk Sinan , Kant Aydın , Arslan Mustafa , Karakoc Hanife Nur , Yılmaz Gürdal
Published: March 2021

Background/Aims: The COVID-19 disease, which was declared epidemic by the WHO, is a global emergency public health problem. Patients with extrapulmonary symptoms are the group of patients who should be considered for person-to-person transmission in the community. In our study, it was aimed to investigate the characteristics of patients with COVID-19-related diarrhea symptoms. Materials and Methods: The study was conducted retrospectively in CO­VID-19 rtRT-PCR-positive patients in 5 medical centers. Three or more loose/liquid stools per day or increased number of defecations compared to normal defecation were defined as diarrhea. The patients were analyzed in 2 groups as those with and without diarrhea. Results: One thousand eighty-six patients were included in the study. Seventy-eight (7.2%) of the patients had diarrhea. Diarrhea was watery in 54 (69.2%) patients while with blood and mucus in 18 (23.1%) patients. Diarrhea continued for an average of 5.2 ± 1.6 (2–11) days. The clinical and laboratory findings of patients with diarrhea were more serious than those without diarrhea. Diarrhea is more common in the elderly and people with comorbid disease, and patients with diarrhea had higher CMI score and CRP and higher complaints of fever, cough, shortness of breath, myalgia, and fatigue. Conclusions: The presence of diarrhea should indicate a suspected COVID-19 infection and suggest testing for early diagnosis of the disease. It should be kept in mind that the course of the disease may be more severe in these patients, and precautions should also be taken in terms of fecal transmission during discharge.
Novel Biomarkers in the Diagnosis of Benign and Malignant Gastrointestinal Diseases
Authors: Jonaitis Paulius , Kiudelis Vytautas , Streleckiene Greta , Gedgaudas Rolandas , Skieceviciene Jurgita , Kupcinskas Juozas
Published: March 2021

Background: Various noninvasive biomarkers have been used in the diagnosis, prognosis, and treatment of different gastrointestinal (GI) diseases for years. Novel technological developments and profound perception of molecular processes related to GI diseases over the last decade have allowed researchers to evaluate genetic, epigenetic, and many other potential molecular biomarkers in different diseases and clinical settings. Here, we present a review of recent and most relevant articles in order to summarize major findings on novel biomarkers in the diagnosis of benign and malignant GI diseases. Summary: Genetic variations, noncoding RNAs (ncRNAs), cell-free DNA (cfDNA), and microbiome-based biomarkers have been extensively analyzed as potential biomarkers in benign and malignant GI diseases. Multiple single-nucleotide polymorphisms have been linked with a number of GI diseases, and these observations are further being used to build up disease-specific genetic risk scores. Micro-RNAs and long ncRNAs have a large potential as noninvasive biomarkers in the management of inflammatory bowel diseases and GI tumors. Altered microbiome profiles were observed in multiple GI diseases, but most of the findings still lack translational clinical application. As of today, cfDNA appears to be the most potent biomarker for early detection and screening of GI cancers. Key Messages: Novel noninvasive molecular biomarkers show huge potential as useful tools in the diagnostics and management of different GI diseases. However, the use of these biomarkers in real-life clinical practice still remains limited, and further large studies are needed to elucidate the ultimate role of these potential noninvasive clinical tools.
Asma infantil: Efectos inmunomoduladores de los liofilizados bacterianos
Authors: Solari Patricia Ximena
Published: March 2021

Background: Polyvalent Mechanical Bacterial Lysate (PMBL®) contains antigens of bacteria responsible for respiratory infections. PMBL® has been proven to reduce the number of respiratory infections, and in its use, immunological benefits have been seen in allergic patients. PMBL® activates both innate and specific immune responses. The lysate induces dendritic cells, T and B lymphocytes and IgA secretion, as well as the production of antibodies directed against administered bacterial antigens. Moreover, it increases the response against other bacteria and viruses. The immunologic mechanism of lysate’s action is not yet clearly determined. The objective of this study was to assess the effect of PMBL® on T cells in children with allergic asthma. Methods: This study was a part of the EOLIA study. Herein, 49 children with allergic asthma and house dust mites allergy were included: 21 in PMBL® and 28 in the Placebo group, both, drug and placebo were administered sublingually. The tests were done at baseline and 12 weeks after the last tablet intake. The lymphocytes CD45+, lymphocytes T CD3+, CD3+CD25+, CD3+CD69+, Th CD3+CD4+, CD4+CD25+, CD4+CD25+ high, CD4+CD69+, Treg CD4+CD25+FOXP3, Tc CD3+CD8+, CD8+CD25+, CD8+CD69+, NK-like T CD3+CD16+CD56+ and NK cells CD3−CD16+CD56+ were described. Results: At baseline, no significant differences between groups relative to blood count cells were observed, except for eosinophils. After 12 weeks, we observed an increase of T lymphocytes count. In addition, CD4+CD25+FOXP3+, CD8+ and CD3−CD16+CD56+ and (insignificantly) Th count increased. However, CD69+ and CD25+ subset of CD3+ significantly decreased. Conclusions: The EOLIA study demonstrated that PMBL® administration 10 days per month for 3 months changed the panel of T lymphocytes. Trial registration Clinical Trial Registration: This study was a part of the EOLIA (Efficacy Of mechanical bacterial Lysate In Allergic children), a clinical study NCT02541331. Frederic Durmont, MD Lallemand Pharma International AG. Date of registration 09/08/2013. URL of trial registry record: https://clinicaltrials.gov/ct2/show/study/NCT02541331.
MicroRNA-Mediated Drug Repurposing Unveiled Potential Candidate Drugs for Prolactinoma Treatment
Authors: Aydin Busra , Arslan Sema , Bayraklı Fatih , Karademir Betul , Arga Kazim Yalcin
Published: March 2021

Introduction: Prolactinomas, also called lactotroph adenomas, are the most encountered type of hormone-secreting pituitary neuroendocrine tumors in the clinic. The preferred first-line therapy is a medical treatment with dopamine agonists (DAs), mainly cabergoline, to reduce serum prolactin levels, tumor volume, and mass effect. However, in some cases, patients have displayed DA resistance with aggressive tumor behavior or are faced with recurrence after drug withdrawal. Also, currently used therapeutics have notorious side effects and impair the life quality of the patients. Methods: Since the amalgamation of clinical and laboratory data besides tumor histopathogenesis and transcriptional regulatory features of the tumor emerges to exhibit essential roles in the behavior and progression of prolactinomas; in this work, we integrated mRNA- and microRNA (miRNA)-level transcriptome data that exploit disease-specific signatures in addition to biological and pharmacological data to elucidate a rational prioritization of pathways and drugs in prolactinoma. Results: We identified 8 drug candidates through drug repurposing based on mRNA-miRNA-level data integration and evaluated their potential through in vitro assays in the MMQ cell line. Seven repurposed drugs including 5-fluorocytosine, nortriptyline, neratinib, puromycin, taxifolin, vorinostat, and zileuton were proposed as potential drug candidates for the treatment of prolactinoma. We further hypothesized possible mechanisms of drug action on MMQ cell viability through analyzing the PI3K/Akt signaling pathway and cell cycle arrest via flow cytometry and Western blotting. Discussion: We presented the transcriptomic landscape of prolactinoma through miRNA and mRNA-level data integration and proposed repurposed drug candidates based on this integration. We validated our findings through testing cell viability, cell cycle phases, and PI3K/Akt protein expressions. Effects of the drugs on cell cycle phases and inhibition of the PI3K/Akt pathway by all drugs gave us promising output for further studies using these drugs in the treatment of prolactinoma. This is the first study that reports miRNA-mediated repurposed drugs for prolactinoma treatment via in vitro experiments.
Reported and Unreported Potentially Important Incidental Findings in Urgent Nonenhanced Abdominal CT for Renal Colic
Authors: Belloni Elena , Tentoni Stefania , Fiorina Ilaria , Bortolotto Chandra , Bottinelli Olivia , Cellina Michaela , Gibelli Daniele , Rosti Cristina , Preda Lorenzo , Calliada Fabrizio , Scagnelli Paola
Published: March 2021

Objective: The aim of the study was to retrospectively evaluate the prevalence of reported and unreported potentially important incidental findings (PIFs) in consecutive nonenhanced abdominal CTs performed specifically for renal colic in the urgent setting. Methods: One radiologist, blinded to the finalized report, retrospectively re-evaluated nonenhanced abdominal CTs performed from January to December 2017 on adult patients from the emergency department with the specific request of urgent evaluation for renal colic, searching for PIFs. Results: The CTs of 312 patients were included in the study. Thirty-eight findings were reported in 38 different CTs, whereas the re-evaluation added 47 unreported findings in 47 different CTs, adding to total of 85 findings (27%). The difference in the proportion of reported and unreported PIFs between the original report and re-evaluation was significant (p < 0.001). No significant difference was found between the age of patients with and without reported findings. The proportion of potentially important findings did not vary significantly among the 3 shifts in the original report and in re-evaluation. The most frequent findings, both reported and unreported, were pleural effusion, lymphadenopathies, and liver nodules. Conclusions: Potentially important additional findings are frequently present in urgent nonenhanced abdominal CTs performed for renal colic, and many are not described in the finalized reports. Radiologists should take care not to underreport PIFs even in the urgent setting because of the possible consequences on the patient’s health and in order to avoid legal issues, while at the same time satisfying the need for timely and efficient reporting.
The State of Peptide Receptor Radionuclide Therapy and Its Sequencing among Current Therapeutic Options for Gastroenteropancreatic Neuroendocrine Tumors
Authors: Raymond Lauren M. , Korzun Tetiana , Kardosh Adel , Kolbeck Kenneth J. , Pommier Rodney , Mittra Erik S.
Published: March 2021

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are the most common form of neuroendocrine neoplasia, but there is no current consensus for the sequencing of approved therapies, particularly with respect to peptide receptor radionuclide therapy (PRRT). This comprehensive review evaluates the data supporting approved therapies for GEP-NETs and recommendations for therapeutic sequencing with a focus on how PRRT currently fits within sequencing algorithms. The current recommendations for PRRT sequencing restrict its use to metastatic, inoperable, progressive midgut NETs; however, this may change with emerging data to suggest that PRRT might be beneficial as neoadjuvant therapy for inoperable tumors, is more tolerable than other treatment modalities following first-line standard dose somatostatin analogs, and can be used as salvage therapy after disease relapse following prior successful cycles of PRRT. PRRT has also been shown to reduce tumor burden, improve quality of life, and prolong the time to disease progression in a broad spectrum of patients with GEP-NETs. As the various potential benefits of PRRT in GEP-NET therapy continues to expand, it is necessary to review and critically evaluate our treatment algorithms for GEP-NETs.
Adverse Pregnancy Outcomes and Cardiovascular Disease Risk: Unique Opportunities for Cardiovascular Disease Prevention in Women: A Scientific Statement From the American Heart Association
Authors: Parikh Nisha I. , Gonzalez Juan M. , Anderson Cheryl A.M. , Judd Suzanne E. , Rexrode Kathryn M. , Hlatky Mark A. , Gunderson Erica P. , Stuart Jennifer J. , Vaidya Dhananjay ,   On behalf of the American Heart Association Council on Epidemiology and Prevention; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; and the Stroke Council
Published: March 2021

This statement summarizes evidence that adverse pregnancy outcomes (APOs) such as hypertensive disorders of pregnancy, preterm delivery, gestational diabetes, small-for-gestational-age delivery, placental abruption, and pregnancy loss increase a woman’s risk of developing cardiovascular disease (CVD) risk factors and of developing subsequent CVD (including fatal and nonfatal coronary heart disease, stroke, peripheral vascular disease, and heart failure). This statement highlights the importance of recognizing APOs when CVD risk is evaluated in women, although their value in reclassifying risk may not be established. A history of APOs is a prompt for more vigorous primordial prevention of CVD risk factors and primary prevention of CVD. Adopting a heart-healthy diet and increasing physical activity among women with APOs, starting in the postpartum setting and continuing across the life span, are important lifestyle interventions to decrease CVD risk. Lactation and breastfeeding may lower a woman’s later cardiometabolic risk. Black and Asian women experience a higher proportion APOs, with more severe clinical presentation and worse outcomes, than White women. More studies on APOs and CVD in non-White women are needed to better understand and address these health disparities. Future studies of aspirin, statins, and metformin may better inform our recommendations for pharmacotherapy in primary CVD prevention among women who have had an APO. Several opportunities exist for health care systems to improve transitions of care for women with APOs and to implement strategies to reduce their long-term CVD risk. One proposed strategy includes incorporation of the concept of a fourth trimester into clinical recommendations and health care policy.
Subtypes of Preeclampsia: Recognition and Determining Clinical Usefulness
Authors: Roberts James M. , Rich-Edwards Janet W. , McElrath Thomas F. , Garmire Lana , Myatt Leslie ,   for the Global Pregnancy Collaboration
Published: March 2021

The concept that preeclampsia is a multisystemic syndrome is appreciated in both research and clinical care. Our understanding of pathophysiology recognizes the role of inflammation, oxidative and endoplasm reticulum stress, and angiogenic dysfunction. Yet, we have not progressed greatly toward clinically useful prediction nor had substantial success in prevention or treatment. One possibility is that the maternal syndrome may be reached through different pathophysiological pathways, that is, subtypes of preeclampsia, that in their specificity yield more clinical utility. For example, early and late onset preeclampsia are increasingly acknowledged as different pathophysiological processes leading to a common presentation. Other subtypes of preeclampsia are supported by disparate clinical outcomes, long-range prognosis, organ systems involved, and risk factors. These insights have been supplemented by discovery-driven methods, which cluster preeclampsia cases into groups indicating different pathophysiologies. In this presentation, we review likely subtypes based on current knowledge and suggest others. We present a consideration of the requirements for a clinically meaningful preeclampsia subtype. A useful subtype should (1) identify a specific pathophysiological pathway or (2) specifically indicate maternal or fetal outcome, (3) be recognizable in a clinically useful time frame, and (4) these results should be reproducible and generalizable (but at varying frequency) including in low resource settings. We recommend that the default consideration be that preeclampsia includes several subtypes rather than trying to force all cases into a single pathophysiological pathway. The recognition of subtypes and deciphering their different pathophysiologies will provide specific targets for prevention, prediction, and treatment directing personalized care.
Associations Between Relative Morning Blood Pressure, Cerebral Blood Flow, and Memory in Older Adults Treated and Controlled for Hypertension
Authors: Noriega de la Colina Adrián , Badji Atef , Robitaille-Grou Marie-Christine , Gagnon Christine , Boshkovski Tommy , Lamarre-Cliche Maxime , Joubert Sven , Gauthier Claudine J. , Bherer Louis , Cohen-Adad Julien , Girouard Hélène
Published: March 2021

Hypertension, elevated morning blood pressure (BP) surges, and circadian BP variability constitute risk factors for cerebrovascular events. Nevertheless, while evidence indicates that hypertension is associated with cognitive dysfunctions, the link between BP variability and cognitive performance during aging is not clear. The purpose of this study is to determine the interaction between relative morning BP, cerebral blood flow (CBF) levels, and cognitive performance in hypertensive older adults with controlled BP under antihypertensive treatment. Eighty-four participants aged between 60 and 75 years old were separated into normotensive (n=51) and hypertensive (n=33) groups and underwent 24-hour ambulatory BP monitoring. They were also examined for CBF in the gray matter (CBF-GM) by magnetic resonance imaging and 5 cognitive domains: global cognition, working memory, episodic memory, processing speed, and executive functions. There was no difference in cognitive performance and CBF between normotensive and controlled hypertensive participants. Through a sensitivity analysis, we identified that, among relative morning BP variables, the best fit for CBF values in this cohort was the morning-evening difference in BP. The relative morning BP was negatively associated with CBF-GM in these hypertensive older adults only. In turn, CBF-GM levels were negatively associated with working and episodic memory scores in hypertensive older adults. This is the first extended study demonstrating an association between high relative morning BP and lower levels of CBF-GM, including the further impact of CBF-GM levels on the cognitive performance of specific domains in a community-based cohort of older adults with hypertension.
Maternal Angiotensin Increases Placental Leptin in Early Gestation via an Alternative Renin-Angiotensin System Pathway
Authors: Nonn Olivia , Fischer Cornelius , Geisberger Sabrina , El-Heliebi Amin , Kroneis Thomas , Forstner Désirée , Desoye Gernot , Staff Anne Cathrine , Sugulle Meryam , Dechend Ralf , Pecks Ulrich , Kollmann Martina , Stern Christina , Cartwright Judith E. , Whitley Guy S. , Thilaganathan Basky , Wadsack Christian , Huppertz Berthold , Herse Florian , Gauster Martin
Published: March 2021

Various studies found an association of different renin-angiotensin system (RAS) components with gestational duration and preterm birth, as well as with preeclampsia. Approximately 25% of first-time pregnant women develop a mild to severe hypertension in pregnancy or even preeclampsia. Based on recently published single-cell RNA-sequencing, we hypothesized an alternative RAS function in placenta and furthermore, an implication in hypertensive disorders in pregnancy.

Placental RAS expression and localization was analyzed via quantitative polymerase chain reaction and in situ mRNA padlock probes. Tissue was collected from first-trimester elective termination (n=198), from healthy third-trimester controls (n=54), from early-onset preeclamptic (n=54) and age-matched controls (n=29), as well as first-trimester placentae from women with a high uterine artery resistance index (high-risk for preeclampsia, n=9) and controls (n=8). Serum levels of Ang (angiotensin) I to IV from women before and after conception were measured via mass spectrometry (n=10). Placental explants were cultured in 2.5% oxygen with Ang II, candesartan, and leptin. Seahorse XF96 MitoStress assays assessed trophoblast metabolism.

Here, we show that maternal angiotensin acts on placental LNPEP (leucine aminopeptidase), that is, angiotensin IV-receptor and fetal angiotensin on placental AGTR1 (angiotensin II receptor type 1). Maternal circulating RAS shifts towards Ang IV in pregnancy. Ang IV decreases trophoblastic mitochondrial respiration and increases placental leptin via placental LNPEP. Lower placental LNPEP in preeclampsia and in first-trimester patients at high-risk for preeclampsia suggests a new alternative route in maternal RAS signaling and may contribute to hypertension and disease in pregnancy.

The study shows how hypertensive disorders in pregnancy may be connected metabolic alterations that finally seem to contribute to the multifactorial disease in pregnancy, preeclampsia.
Cardiovascular Protection With Sodium-Glucose Cotransporter-2 Inhibitors and Mineralocorticoid Receptor Antagonists in Chronic Kidney Disease
Authors: Sarafidis Pantelis , Papadopoulos Christodoulos E. , Kamperidis Vasilios , Giannakoulas George , Doumas Michael
Published: March 2021

Chronic kidney disease (CKD) and cardiovascular disease are intimately linked. They share major risk factors, including age, hypertension, and diabetes, and common pathogenetic mechanisms. Furthermore, reduced renal function and kidney injury documented with albuminuria are independent risk factors for cardiovascular events and mortality. In major renal outcome trials and subsequent meta-analyses in patients with CKD, ACE (angiotensin-converting enzyme) inhibitors and ARBs (angiotensin II receptor blockers) were shown to effectively retard CKD progression but not to significantly reduce cardiovascular events or mortality. Thus, a high residual risk for cardiovascular disease progression under standard-of-care treatment is still present for patients with CKD. In contrast to the above, several outcome trials with SGLT-2 (sodium-glucose cotransporter-2) inhibitors and MRAs (mineralocorticoid receptor antagonists) clearly suggest that these agents, apart from nephroprotection, offer important cardioprotection in this population. This article discusses existing evidence on the effects of SGLT-2 inhibitors and MRAs on cardiovascular outcomes in patients with CKD that open new roads in cardiovascular protection of this heavily burdened population.
RYANSQL: Recursively Applying Sketch-based Slot Fillings for Complex Text-to-SQL in Cross-Domain Databases
Authors: Choi DongHyun , Shin Myeong Cheol , Kim EungGyun , Shin Dong Ryeol
Published: March 2021

Text-to-SQL is the problem of converting a user question into an SQL query, when the question and database are given. In this article, we present a neural network approach called RYANSQL (Recursively Yielding Annotation Network for SQL) to solve complex Text-to-SQL tasks for cross-domain databases. Statement Position Code (SPC) is defined to transform a nested SQL query into a set of non-nested SELECT statements; a sketch-based slot filling approach is proposed to synthesize each SELECT statement for its corresponding SPC. Additionally, two input manipulation methods are presented to improve generation performance further. RYANSQL achieved competitive result of 58.2% accuracy on the challenging Spider benchmark. At the time of submission (April 2020), RYANSQL v2, a variant of original RYANSQL, is positioned at 3rd place among all systems and 1st place among the systems not using database content with 60.6% exact matching accuracy. The source code is available at https://github.com/kakaoenterprise/RYANSQL.
Marine Biodiversity Negotiations During COVID-19: A New Role for Digital Diplomacy?
Authors: Vadrot Alice B. M. , Langlet Arne , Tessnow-von Wysocki Ina , Tolochko Petro , Brogat Emmanuelle , Ruiz-Rodríguez Silvia C.
Published: March 2021

Measures related to the COVID-19 pandemic have indefinitely postponed in-person formal international negotiations for a new legally binding instrument under the United Nations Convention on the Law of the Sea on the conservation and sustainable use of marine biological diversity of areas beyond national jurisdiction (BBNJ). As a result, online initiatives have emerged to keep informal dialogue ongoing among both state and nonstate actors. To continue our research on the BBNJ process, we adapted our methodology and conducted a survey in May 2020 exploring the impact of COVID-19 on respondents’ BBNJ-related work and communication. This research note identifies online initiatives and communication channels set up to maintain negotiation momentum and examines the challenges and opportunities of digital diplomacy for multilateral environmental agreement making, as well as the study thereof. We discuss future avenues for global environmental politics research and conclude that digital ethnographies provide an entry point to study some of these dynamics but need to be adapted to the study of negotiation settings and the specific context of multilateral environmental diplomacy.
The Role of Sensory Feedback in Developmental Stuttering: A Review
Authors: Bradshaw Abigail R. , Lametti Daniel R. , McGettigan Carolyn
Published: March 2021

Developmental stuttering is a neurodevelopmental disorder that severely affects speech fluency. Multiple lines of evidence point to a role of sensory feedback in the disorder; this has led to a number of theories proposing different disruptions to the use of sensory feedback during speech motor control in people who stutter. The purpose of this review was to bring together evidence from studies using altered auditory feedback paradigms with people who stutter, in order to evaluate the predictions of these different theories. This review highlights converging evidence for particular patterns of differences in the responses of people who stutter to feedback perturbations. The implications for hypotheses on the nature of the disruption to sensorimotor control of speech in the disorder are discussed, with reference to neurocomputational models of speech control (predominantly, the DIVA model; Guenther et al., 2006; Tourville et al., 2008). While some consistent patterns are emerging from this evidence, it is clear that more work in this area is needed with developmental samples in particular, in order to tease apart differences related to symptom onset from those related to compensatory strategies that develop with experience of stuttering.
Power and Globalization in Africa: Perceptions of Barriers to Fair Economic Development in Kenya
Authors: Ngendakurio John Bosco
Published: March 2021

This article seeks to reveal the primary barriers to fair economic development based on Kenyans’ perceptions of power and globalization. This search was initially sparked by the seeming disinterest of First World scholars to understand the reasons why poor countries benefit so little from the global market as reflected in a subsequent lack of a wide-ranging existing literature about the subject. The literature suggests that global capitalism is dominated by a powerful small elite, the so-called Transnational Capitalist Class (TCC), but how does this relate to Kenya and Africa in general? We know that the TCC has strong connections to financial capital and wealthy transnational corporations. It also pushes neo-liberalism, which becomes the taken-for-granted everyday language and culture that justifies state policies that result in a further class polarization between the rich and poor.

Using Kenya as a case study, this article draws on original qualitative research involving face-to-face interviews with Kenyan residents in different sectors who spoke freely about what they perceive to be Kenya’s place in the world order. My interview results show that, on top of the general lack of economic power in the world order, the main barriers to Africa’s performance are neo-colonial and imperialist practices, poor technology, poor infrastructure, general governance issues, and purchasing power.
White Supremacy: Will the Present be Prologue?
Authors: Westmoreland Mark William
Published: March 2021

In recent years, there has been a rethinking of the concept of white privilege and a development of new concepts like white fragility. At the same time, discourse around ‘white supremacy’ has mostly remained stagnant. Some claim it is anachronistic and no longer applicable. Others fear it will discourage whites from supporting the quest for racial justice. In this article, I advocate for using the term ‘white supremacy’ to name the problem that racial justice theorists and activists seek to dismantle. More specifically, I utilize the work of Charles Mills to defend the use of ‘white supremacy’ against Marxist critics.
Bryozoa from the reefs off the Amazon River mouth: checklist, thirteen new species, and notes on their ecology and distribution
Authors: RAMALHO LAÍS V. , MORAES FERNANDO C. , SALGADO LEONARDO T. , BASTOS ALEX C. , MOURA RODRIGO L.
Published: March 2021

The reef system off the Amazon River mouth extends from Amapá state to Maranhão state along the Brazilian Equatorial Margin, encompassing more than 10,000 km2 of rhodolith beds and high-relief hard structures on the outer shelf and upper slope. This unique hard bottom mosaic is remarkable for being influenced by the turbid and hyposaline plume from the world’s largest river, and also for representing a connectivity corridor between the Caribbean and Brazil. Bryozoans were recently recognized as major reef builders in the Southwestern Atlantic, but their diversity off the Amazon River mouth remained unknown. Here, we report on recent collections obtained from 23 to 120 m depth in Northern Brazil. Sixty-five bryozoan taxa were characterized using scanning electron microscopy, including 57, five and three taxa of Cheilostomatida, Cyclostomatida and Ctenostomatida, respectively. Cribrilaria smitti and three genera (Cranosina, Glabrilaria and Thornelya) are new records for Brazil, and 13 new species are herein described: Antropora cruzeiro n. sp., Cranosina gilbertoi n. sp., Cribrilaria lateralis n. sp., Crisia brasiliensis n. sp., Glabrilaria antoniettae n. sp., Micropora amapaensis n. sp., Parasmittina amazonensis n. sp., Plesiocleidochasma arcuatum n. sp., Poricella bifurcata n. sp., Pourtalesella duoavicularia n. sp., Stephanollona domuspusilla n. sp., Therenia dianae n. sp., and Thornelya atlanticoensis n. sp. Our results highlight the biodiversity significance of the Amazon reefs and the need for more comprehensive sampling to clarify the role of bryozoans in modern turbid-zone reefs and rhodolith beds.
The invisibile becomes visible: X-ray micro-CT reconstruction of Aneurus damzeni sp. nov. (Hemiptera: Heteroptera: Aradidae) from Eocene Baltic amber
Authors: HEISS ERNST , KAIRIŠS KRISTAPS , BUKEJS ANDRIS
Published: March 2021

The subfamily Aneurinae of the flat bug family Aradidae (Hemiptera: Heteroptera) contains about 150 extant species assigned to seven genera, and seven fossil species of which six were described from Eocene Baltic amber and one from Cretaceous Burmese amber. A new species Aneurus damzeni sp. nov. from Baltic amber is described and illustrated using X-ray micro-computed tomography (μCT) reconstructing concealed morphological characters. A key to all five extant and fossil Aneurinae species with triangular scutellum is provided.
A poorly known species and new records of Plecoptera from the Eastern Tien Shan, Xinjiang Uygur Autonomous Region, China
Authors: TESLENKO VALENTINA A. , PALATOV DMITRY M.
Published: March 2021

Nemoura lepnevae Zhiltzova, 1971, Amphinemura mirabilis turkestanica Zhiltzova, 1978, Capnia s.l. longicauda Zhiltzova, 1969 and Mesoperlina pecirkai Klapálek, 1921 are reported for the stonefly fauna of China for the first time. The species were collected in the Bogdo-Ula and Karlyktag Ranges of the Eastern Tian Shan Mountains, the Xinjiang Uygur Autonomous Region. In addition, a detailed redescription of Filchneria wusuensis Chen, 2019 including new illustrations is provided.
A new species of driftwood catfish Centromochlus Kner, 1858 (Siluriformes, Auchenipteridae, Centromochlinae) from Tocantins-Araguaia River drainage
Authors: COELHO FERNANDA L. , CHAMON CARINE C. , SARMENTO-SOARES LUISA M.
Published: March 2021

The genus Centromochlus includes eight catfish species in the Amazon and Orinoco river systems: C. schultzi from Xingu and Tocantins-Araguaia rivers; C. melanoleucus from Tapajós and Teles Pires rivers; C. macracanthus from Negro River; C. orca from Nhamundá River; C. heckelii and C. existimatus from Amazon and additionally at the Essequibo rivers; C. carolae and C. musaica from Orinoco River system. Recent field expeditions and collection examination revealed an undescribed species of Centromochlinae that has compatible features with Centromochlus. We herein describe a new species of Centromochlus from the Tocantins-Araguaia River drainage, diagnosed among most Centromochlinae by having a vermiculated color pattern on the dorsum and included in Centromochlus by sharing the derived features: ventrolateral position of eye socket; sphenotic notched for the exit of infraorbital canal; and posterior serrations along pectoral-fin spine numerous. The new species is diagnosed from congeners by having the pectoral-fin spine with dark bars, alternating with light bars (vs. pectoral-fin spine with light and uniform color in all Centromochlus); and it is further distinguished from its congeners (except C. carolae) by the ventral surface of head moderate to largely pigmented (vs. ventral surface of head unpigmented in C. heckelii, C. existimatus, C. orca, C. musaicus, C. schultzi, with few scattered dark chromatophores in C. macracanthus and C. melanoleucus; see diagnosis). A discussion about the systematics of the genus, plus the conservation status of the new species, and an identification key to species of Centromochlus, are also provided.