bluuebunny/crossref_metadata_2025 huggingface dataset:
Atrial functional mitral regurgitation
Authors: Hoit Brian D.
Published: July 2020

Purpose of review

To review the prevalence and prognosis of atrial functional mitral regurgitation (AFMR), the distinctive echocardiographic and mechanistic findings, and the therapeutic implications of this newly described disorder.

Recent findings

Initial studies identified an association between atrial fibrillation, mitral annular dilation, and significant mitral regurgitation despite a normal mitral valve and left ventricle. Accumulating data suggest that AFMR is not rare and may have a prognosis as poor as functional MR associated with LV remodeling. Echocardiography has played an important role in understanding the unique pathophysiology of AFMR, and proposed mechanisms include not only atrial remodeling, but structural and functional abnormalities of the LV (HFpEF shares a common pathophysiology) and insufficient leaflet growth. Timely rhythm control of atrial fibrillation and strategies that reduce diastolic pressure, left atrial and mitral annular enlargement, and that favorably affect mitral leaflet adaptation, are promising preventive and treatment options that warrant clinical study.

Functional mitral regurgitation may be atrial in origin and should be considered in patients with (particularly long-standing) atrial fibrillation and in those with HFpEF.
Opportunities for improved cardiovascular disease prevention in oncology patients
Authors: Bravo-Jaimes Katia , Marcellon Roselande , Varanitskaya Liubou , Kim Peter Y. , Iliescu Cezar , Gilchrist Susan C. , Baldassarre Lauren A. , Manisty Charlotte , Ghosh Arjun K. , Guha Avirup , Lopez-Mattei Juan C.
Published: July 2020

Purpose of review

Cancer patients often have cardiovascular risk factors at the time of cancer diagnosis, which are known to increase the risk of cardiotoxicity. Cancer survivors have significantly higher cardiovascular risk. Current cardiovascular disease prevention guidelines are based on studies that largely excluded these patients. We reviewed recent data regarding cardiovascular disease prevention in this population.

Recent findings

Nonpharmacologic therapies aiming to reduce ‘lifestyle toxicity’ produced by cancer treatments have demonstrated potential to decrease the incidence of adverse outcomes. Exercise before, during and after cancer treatment not only promotes higher quality of life and cardiorespiratory fitness but also reduces adverse cardiovascular outcomes. Lipid and cardiometabolic disease management is paramount but predominantly based on data that excludes these populations of cancer patients and survivors.

A comprehensive approach including medical evaluation, prescriptive exercise, cardiac risk factor modification, education, counseling, pharmacologic and behavioral interventions are needed in cancer patients. These interventions constitute the core of cardio-oncology rehabilitation programs, which if implemented appropriately may help reduce cardiovascular events in this population. Knowledge gaps in these areas are starting to be addressed by ongoing clinical trials.
Treatment-resistant hypertension in the hemodialysis population: a 44-h ambulatory blood pressure monitoring-based study
Authors: Mallamaci Francesca , Torino Claudia , Sarafidis Pantelis , Ekart Robert , Loutradis Charalampos , Siamopoulos Kostas , Del Giudice Antonio , Aucella Filippo , Morosetti Massimo , Raptis Vasilios , Bikos Athanasios , Papagianni Aikaterini , Balafa Olga , Pappas Efthymios , Tripepi Rocco , Marino Carmela , Tripepi Giovanni , Ferro Charles , Malyszko Jolanta , Dekker Friedo W. , Jager Kitty J. , London Gérard M. , Zoccali Carmine
Published: July 2020

Background:

Uncontrolled hypertension notwithstanding the use of at least three drugs or hypertension controlled with at least four drugs, the widely accepted definition of treatment-resistant hypertension (TRH), is considered as a common problem in the hemodialysis population. However, to date there is no estimate of the prevalence of this condition in hemodialysis patients.

Method:

We estimated the prevalence of TRH by 44-h ambulatory BP monitoring (ABPM) in 506 hemodialysis patients in 10 renal units in Europe included in the registry of the European Renal and Cardiovascular Medicine (EURECAm,), a working group of the European Association, European Dialysis and Transplantation Association (ERA EDTA). In a sub-group of 114 patients, we tested the relationship between fluid overload (Body Composition monitor) and TRH.

Results:

The prevalence of hypertension with 44-h ABPM criteria was estimated at 85.6% (434 out of 506 patients). Of these, 296 (58%) patients were classified as uncontrolled hypertensive patients by 44-h ABPM criteria (≥130/80 mmHg). Two hundred and thirteen patients had uncontrolled hypertension while on treatment with less than three drugs and 210 patients were normotensive while on drug therapy (n = 138) or off drug treatment (n = 72). The prevalence of TRH was 24% (93 among 386 treated hypertensive patients). The prevalence of predialysis fluid overload was 33% among TRH patients, 34% in uncontrolled hypertensive patients and 26% in normotensive patients. The vast majority (67%) of hemodialysis patients with TRH had no fluid overload.

Conclusion:

TRH occurs in about one in four treated hypertensive patients on hemodialysis. Fluid overload per se only in part explains TRH and the 67% of these patients show no fluid overload.
Air pollution-associated blood pressure may be modified by diet among children in Guangzhou, China
Authors: Zhang Jingshu , Cai Li , Gui Zhaohuan , Wang Suhan , Zeng Xia , Lai Lijuan , Lv Yajie , Tan Kaiyun , Wang Hui , Huang Cunrui , Chen Yajun
Published: July 2020

Objectives:

To assess the associations between long-term air pollution exposure and blood pressure in children, and to explore the modifying effects of diet on prehypertension and hypertension.

Methods:

We evaluated 7225 primary school children aged 6–12 years from Guangzhou, China, in 2017. The blood pressure was measured objectively. The individual 1-year average concentration of particles with an aerodynamic diameter of 2.5 μm or less or 10 μm or less (PM2.5, PM10), sulfur dioxide (SO2), and ozone (O3) before each blood pressure measurement were calculated by inverse distance weighting interpolation according to each home address. Generalized linear mixed-effects models were used to examine the health effects and potential effect modifications by diet factors after adjusting for covariates.

Results:

The results showed that the estimated increase in mean SBP was 0.92 mmHg (95% CI 0.05–1.79) per interquartile range increase in O3. An interquartile range increase in the 1-year mean of SO2 and O3 was associated with odds ratios of 1.26 (95% CI 1.04–1.52) and 1.20 (95% CI 1.06–1.35) for prehypertension, respectively. In addition, an interquartile range increase in PM2.5, SO2, and O3 exposure was positively associated with hypertension, with odds ratios of 1.33 (95% CI 1.11–1.61), 1.70 (95% CI 1.33–2.16), and 1.48 (95% CI 1.20–1.83), respectively. Stronger effect estimates between PM2.5, SO2, and O3 concentration on prehypertension were exhibited among subgroups of children with a higher intake of sugar-sweetened beverages.

Conclusion:

Long-term exposure to PM2.5, SO2, and O3 were associated with higher blood pressure levels in children, and dietary intake might modify these associations.
Sustained Elevation of Intraocular Pressure After Administration of Intravitreal Anti-Vascular Endothelial Growth Factor Agents in Patients With and Without Pseudoexfoliation Syndrome
Authors: Ucgul Ahmet Y. , Aktas Zeynep , Ozgur Armagan , Cubuk Mehmet O. , Hasanreisoglu Murat , Ozdek Sengul , Gurelik Gokhan
Published: July 2020

Précis:

Intravitreal anti-vascular endothelial growth factor therapy resulted in sustained elevation of intraocular pressure (IOP) in 18.6% of patients with coexisting age-related macular degeneration and pseudoexfoliation (PXF) syndrome. The development of sustained elevation of IOP after ~19 injections reflected the cumulative effect of anti-vascular endothelial growth factor injections on IOP.

Purpose:

The purpose of this study was to compare the long-term effect of intravitreal ranibizumab (IVR) and intravitreal bevacizumab (IVB) therapies on IOP in patients with and without PXF syndrome.

Design:

This was a retrospective comparative study.

Patients and Methods:

Data from 412 eyes of 206 patients diagnosed with unilateral neovascular age-related macular degeneration, treated with IVR or IVB, and followed-up for at least 6 months, were retrospectively reviewed. Seventy treated and 70 untreated fellow eyes of 70 patients with bilateral PXF syndrome, and 136 treated and 136 untreated fellow eyes of 136 patients without PXF syndrome were included in this study. Demographic information, clinical findings, total number of IVR and IVB injections, and IOP values at each visit were recorded. Sustained elevation of IOP (SE-IOP) was defined as either an IOP >21 mm Hg or a ≥5 mm Hg increase in IOP from baseline for at least 2 consecutive visits. Baseline and final IOP values in each group were compared using the paired sample t test, and IOP changes in the groups were compared using split-plot analysis of variance. Multivariate logistic regression analysis was used to evaluate the influence of variables on the development of SE-IOP.

Results:

The mean (±SD) age of the patients was 77.53±3.78 years (range, 70 to 83 y), and the mean follow-up was 28.50±16.51 months (range, 6 to 58 mo). The mean number of injections was 15.56±8.01 (range, 5 to 36). The mean baseline and final IOP in treated eyes were 14.82±3.08 and 16.50±3.11 mm Hg, respectively (P<0.001). A higher incidence of SE-IOP and higher final IOP values were observed in PXF-positive eyes receiving IVB compared with the other groups. Seven of the patients required antiglaucomatous treatment. Multivariate logistic regression analysis revealed an increased odds ratio (4.90; P=0.016) of SE-IOP in PXF-positive eyes compared with PXF-negative eyes.

Conclusion:

IVB therapy may cause greater increases in IOP in patients with PXF syndrome. The co-accumulation of PXF material and bevacizumab particles on the trabecular meshwork should be further investigated.
Performance of radiography and single-photon emission computed tomography/computed tomography in painful total hip arthroplasty and impact on arthroplasty survival
Authors: Schuldt Anna , Lehnick Dirk , Agten Christoph A. , Beck Martin , Kist Markus , Bhure Ujwal , del Sol Pérez Lago María , Strobel Klaus
Published: July 2020

Purpose

To investigate the performance of radiography and single-photon emission computed tomography/computed tomography (SPECT/CT) in painful hip arthroplasty regarding loosening and arthroplasty survival.

Methods

Radiography and SPECT/CT reports of 249 painful hip arthroplasties of 191 patients were reviewed. Positive imaging was defined if loosening, infection, and polyethylene wear were found, indicating the need for arthroplasty exchange. Median time from radiograph to operation or last follow-up was 41.3 months (range 0.3–118.4 months). In 67 patients, the performance of radiographs and SPECT/CT regarding loosening was compared with an intraoperative reference standard. The time point of arthroplasty exchange was compared with imaging diagnosis and evaluated with Kaplan–Meier curves.

Results

Exchange of cup, shaft, or both was performed in 76 of 249 arthroplasties. Main diagnoses on SPECT/CT were loosening (n = 94), infection (n = 5), and polyethylene wear (n = 15). In total, 104 patients were SPECT/CT positive compared to 84 patients on radiography. Five-year survival of arthroplasties for radiograph positive and negative arthroplasties was 41.5%/83.4% and 39.3%/90.7% for SPECT/CT, respectively. Prognostic impact regarding arthroplasty exchange was highest in radiograph and SPECT/CT concordant positive patients (hazard ratio 19.7 as compared to radiograph and SPECT/CT negative patients). Sensitivity and specificity in 67 operated patients regarding shaft loosening were 59.4%/80.0% with radiography, 90.6%/68.6% with SPECT/CT (P = 0.002 for sensitivity and P = 0.29 for specificity), and for cup loosening 47.4%/89.6% with radiography and 63.2%/85.4% with SPECT/CT (P = 0.51, respectively, P = 0.63).

Conclusion

In patients with painful hip arthroplasty, positive radiography, and SPECT/CT are associated with poorer arthroplasty survival. Performance regarding loosening is slightly better with SPECT/CT.
Microcrystalline Cellulose and Crospovidone Identified in Placentas With Vaginal Misoprostol Use
Authors: Butler Daniel C. , Presnell Susan Erin , Bruner Evelyn , Page Tyrish , Cuff Ryan , Phillips Angelina
Published: July 2020

Misoprostol is a prostaglandin analog commonly used to induce termination of pregnancy. Clandestine home terminations complicate forensic fetal autopsy when a history of misoprostol use is withheld and the gross and histologic findings are sparse, as is often the case. One hundred thirty-two placentas with no vaginal misoprostol use, low-dose misoprostol use, and high-dose misoprostol use were reviewed for the presence, volume, and locations of microcrystalline cellulose and crospovidone, common tablet fillers in misoprostol tablets. Microcrystalline cellulose and/or crospovidone was identified in 0 (0%) of 88 cases with no vaginal administration or low-dose vaginal administration and 29 (66%) of 44 placentas with high-dose vaginal administration. When identified, microcrystalline cellulose and/or crospovidone is most commonly present on the maternal surfaces of the extraplacental membranes. The presence of microcrystalline cellulose and/or crospovidone was associated with smaller placental weight (Mann-Whitney U, P = 0.019). These fillers have a reasonable sensitivity for high-dose vaginal tablet use and are very specific. Although they are not diagnostic for misoprostol administration, they provide a finding that may prompt additional investigation into the nature of the vaginal tablet administered and the circumstances surrounding birth.
Autopsy Services and Emergency Preparedness of a Tertiary Academic Hospital Mortuary for the COVID-19 Public Health Emergency: The Yale Plan
Authors: McGuone Declan , Sinard John , Gill James R. , Masters Amanda , Liu Chen , Morotti Raffaella , Parkash Vinita
Published: July 2020

Pathology Autopsy and Mortuary Services have been front and center in the severe acute respiratory syndrome coronavirus 2 (SARS-Co-V-2) pandemic. The sheer number of fatalities from the pandemic have been unlike any other in recent memory and needed the rapid creation of new protocols and paradigms to manage the situation. This required rapidly escalating mortuary capacity to manage the increased fatalities from the pandemic with the establishment of lines of communication and networking with governmental entities, institution of new policies for patient flow, and implementation of worker infection control and well-being plans. Autopsies also assumed a crucial role, both to provide insight into the pathomechanisms of a novel disease and to allow tissue retrieval necessary to power research directed towards finding a vaccine. We here outline the plan adopted by the Yale Autopsy and Mortuary Services, in alignment with the institutional mission of high-quality patient care, education, research and health care worker safety and well-being, as the Corona Virus Disease of 2019 (COVID-19) pandemic surged in Connecticut. In the early response phase, ensuring sufficient mortuary capacity necessarily took center stage. As we enter the recovery and plateau phase of the pandemic, setting up a process for a rapid and safe autopsy, that will meet educational and research needs while ensuring the safety of our workforce is being implemented.
Adverse Biology in Adenocarcinoma of the Esophagus and Esophagogastric Junction Impacts Survival and Response to Neoadjuvant Therapy Independent of Anatomic Subtype
Authors: Donlon Noel E. , Elliott Jessie A. , Donohoe Claire L. , Murphy Conor F. , Nugent Tim , Moran Brendan , King Sinead , Ravi Narayanasamy , Reynolds John V.
Published: July 2020

Objective:

The aim of this study was to propose and test a novel adverse pathology classification in AEG.

Background:

Recent scientific advances show genomic and molecular concordance across all AEG types, suggesting a rationale for a biologic classification. We tested a 3-dimension adverse pathology classification across the entire junction and per Siewert anatomic subtype.

Methods:

Of 1625 patients with AEG, 650 underwent radical surgery, 55% post-neoadjuvant therapy (NeoT). Adverse features defined a priori were poor differentiation (PD), lymphatic invasion (LI), vascular invasion (VI), and perineural invasion (PN), with 3 groupings: 0 (no adverse feature), 1 to 2, and 3 to 4. Multivariable logistic and Cox proportional hazards regression were applied.

Results:

For adverse pathology, 31%, 46%, and 23% had 0, 1 to 2, and 3 to 4, respectively. Fifty percent of cases were AEG I, 25% AEG II, and 25% AEG III. Median survival was not reached, 49 and 17 months for 0, 1 to 2, and 3 to 4 adverse pathology, respectively (P < 0.001), and 76, 51, and 34 months for AEG I, II, and III, respectively (P < 0.001); AEG I was significantly (P< 0.001) associated with lower c (y)pT and c (y)pN stages, and LI, VI, PN, and PD (poor vs other). The pathology model was significant for survival along with (y)pT and (y)pN, and predicted response to chemotherapy and chemoradiation irrespective of anatomic subtype (P < 0.001).

Conclusion:

A novel classification using standard pathology as proxy for poor biology is associated with survival and response to therapy. This effect is observed across the entire AEG spectrum, highlighting how biology should be aligned with anatomy in the modern paradigm of AEG management and design of clinical trials.
Patient-derived Organoid Pharmacotyping is a Clinically Tractable Strategy for Precision Medicine in Pancreatic Cancer
Authors: Seppälä Toni T. , Zimmerman Jacquelyn W. , Sereni Elisabetta , Plenker Dennis , Suri Reecha , Rozich Noah , Blair Alex , Thomas Dwayne L. , Teinor Jonathan , Javed Ammar , Patel Hardik , Cameron John L. , Burns William R. , He Jin , Tuveson David A. , Jaffee Elizabeth M. , Eshleman James , Szabolcs Annamaria , Ryan David P. , Ting David T. , Wolfgang Christopher L. , Burkhart Richard A.
Published: July 2020

Objective:

PDAC patients who undergo surgical resection and receive effective chemotherapy have the best chance of long-term survival. Unfortunately, we lack predictive biomarkers to guide optimal systemic treatment. Ex-vivo generation of PDO for pharmacotyping may serve as predictive biomarkers in PDAC. The goal of the current study was to demonstrate the clinical feasibility of a PDO-guided precision medicine framework of care.

Methods:

PDO cultures were established from surgical specimens and endoscopic biopsies, expanded in Matrigel, and used for high-throughput drug testing (pharmacotyping). Efficacy of standard-of-care chemotherapeutics was assessed by measuring cell viability after drug exposure.

Results:

A framework for rapid pharmacotyping of PDOs was established across a multi-institutional consortium of academic medical centers. Specimens obtained remotely and shipped to a central biorepository maintain viability and allowed generation of PDOs with 77% success. Early cultures maintain the clonal heterogeneity seen in PDAC with similar phenotypes (cystic–solid). Late cultures exhibit a dominant clone with a pharmacotyping profile similar to early passages. The biomass required for accurate pharmacotyping can be minimized by leveraging a high-throughput technology. Twenty-nine cultures were pharmacotyped to derive a population distribution of chemotherapeutic sensitivity at our center. Pharmacotyping rapidly-expanded PDOs was completed in a median of 48 (range 18–102) days.

Conclusions:

Rapid development of PDOs from patients undergoing surgery for PDAC is eminently feasible within the perioperative recovery period, enabling the potential for pharmacotyping to guide postoperative adjuvant chemotherapeutic selection. Studies validating PDOs as a promising predictive biomarker are ongoing.
Angioembolization in intra-abdominal solid organ injury: Does delay in angioembolization affect outcomes?
Authors: Chehab Mohamad , Afaneh Amer , Bible Letitia , Castanon Lourdes , Hanna Kamil , Ditillo Michael , Khurrum Muhammad , Asmar Samer , Joseph Bellal
Published: July 2020

INTRODUCTION

Angioembolization (AE) is an integral component in multidisciplinary algorithms for achieving hemostasis in patients with trauma. The American College of Surgeons Committee on Trauma recommends that interventional radiologists be available within 30 minutes to perform emergent AE. However, the impact of the timing of AE on patient outcomes is still not well known. We hypothesized that a delay in AE would be associated with increased mortality and higher blood transfusion requirements in patients with blunt intra-abdominal solid organ injury.

METHODS

A 4-year (2013–2016) retrospective review of the ACS Trauma Quality Improvement Program database was performed. We included adult patients (age, ≥18 years) with blunt intra-abdominal solid organ injury who underwent AE within 4 hours of hospital admission. Patients who underwent operative intervention before AE were excluded. The primary outcome was 24-hour mortality. The secondary outcome was blood product transfusions. Patients were grouped into four 1-hour intervals according to their time from admission to AE. Multivariate regression analysis was performed to accommodate patient differences.

RESULTS

We analyzed 1,009,922 trauma patients, of which 924 (1 hour, 76; 1–2 hours, 224; 2–3 hours, 350; 3–4 hours, 274) were deemed eligible. The mean ± SD age was 44 ± 19 years, and 66% were male. The mean ± SD time to AE was 144 ± 54 minutes, and 92% of patients underwent AE more than 1 hour after admission. Overall 24-hour mortality was 5.2%. On univariate analysis, patients receiving earlier AE had decreased 24-hour mortality (p = 0.016), but no decrease in blood products transfused. On regression analysis, every hour delay in AE was significantly associated with increased 24-hour mortality (p < 0.05).

CONCLUSION

Delayed AE for hemorrhagic control in blunt trauma patients with an intra-abdominal solid organ injury is associated with increased 24-hour mortality. Trauma centers should ensure timeliness of interventional radiologist availability to prevent a delay in vital AE, and it should be a focus of quality improvement projects.

LEVEL OF EVIDENCE

Prognostic, level III.
Resuscitative endovascular balloon occlusion of the aorta for thoracic trauma in the setting of platelet dysfunction: A translational swine study
Authors: Glaser Jacob J. , Neidert Leslie E. , Morgan Clifford G. , Brenner Megan , Stigall Kyle S. , Cardin Sylvain
Published: July 2020

BACKGROUND

In patients with noncompressible torso hemorrhage, antiplatelet medications may lead to worse outcomes. Resuscitative endovascular balloon occlusion of the aorta (REBOA) may potentially stabilize these patients, but currently, major thoracic bleeding is a contraindication. The goal of this study was to determine if REBOA use for shock with major thoracic bleeding has worse outcomes in the setting of platelet dysfunction (PD).

METHODS

Forty-one male Yorkshire swine (60–80 kg) underwent a 30% hemorrhage and then were randomized to three thoracic injuries, with and without zone 1 REBOA occlusion: pulmonary parenchymal injury (PI), thoracic venous injury (VI), or subclavian artery injury (AI). All animals were given aspirin to produce PD. Following hemorrhage, thoracic injuries were induced (T0) and allowed to bleed freely. Resuscitative endovascular balloon occlusion of the aorta groups had zone 1 occlusion, with deflation at T30. All groups received whole blood resuscitation at T30 and were euthanized at T90. Survival, total blood loss, hemodynamics, and arterial blood gas parameters were analyzed.

RESULTS

The PD-VI-REBOA group had 87.5% survival where PD-VI survival was 28.6%. No difference in survival was seen in the PI or AI groups. The PD-VI-REBOA group had total blood loss of 575.0 ± 339.1 mL, which was less than the PD-VI group (1,086.0 ± 532.1 mL). There was no difference in total thoracic blood loss in the PI and AI groups with the addition of REBOA. All groups showed an equivalent decrease in HCO3 and base excess and increase in lactate at the end of the 30-minute prehospital phase.

CONCLUSION

In this study, zone 1 REBOA improved survival and decreased blood loss with major VI, where no differences were seen in parenchymal and subclavian artery injuries. For thoracic bleeding without surgical capability, outcomes may be improved with REBOA, and these findings challenge current guidelines stating the contraindication of REBOA use in this setting.
Value of a Panel of 6 Serum Biomarkers to Differentiate Between Healthy Controls and Mild Cognitive Impairment Due to Alzheimer Disease
Authors: Schipke Carola G. , Menne Felix , Rubow Stella , Sigle Jörg-Peter , Peters Oliver , Grimmer Timo
Published: July 2020

Background:

There is considerable evidence suggesting that inflammatory responses may be involved in the neurodegenerative cascade of Alzheimer disease (AD). Blood-based biomarker analysis of inflammatory markers indicative of dementia could serve as a minimally invasive and easy-to-administer diagnostic tool in primary care.

Material and Methods:

The authors quantified 6 markers (brain-derived neurotrophic factor, insulin-like growth factor 1, vascular endothelial growth factor, transforming growth factor-beta type 1, monocyte chemoattractant protein 1, and interleukin-18) in blood serum of 68 healthy blood donors (controls), 42 patients with AD at the dementia stage, 55 patients with AD at the stage of mild cognitive impairment (MCI-AD), and 25 patients with MCI non-AD. All patients have been fully characterized, including AD biomarker analyses in cerebrospinal fluid. Data were analyzed in an algorithm that was trained, validated, and then used for dichotomous classification of unknown data into data sets suspicious and not suspicious of AD.

Results:

Using this algorithm, 47 of 55 MCI-AD (85.5%) and 20 of 25 MCI non-AD (80%) cases were classified as suspicious of AD.

Conclusions:

This panel of 6 markers in blood serum may indicate underlying neurodegenerative processes in patients with AD at the MCI stage. The authors assume that a deranged equilibrium of neuroprotective and inflammatory processes is an overall major cause for neurodegeneration and cognitive decline.
Analysis of the small chromosomalPrionium serratum(Cyperid) demonstrates the importance of a reliable method to differentiate between mono- and holocentricity
Authors: Baez M. , Kuo Y.T. , Dias Y. , Souza T. , Boudichevskaia A. , Fuchs J. , Schubert V. , Vanzela A.L.L. , Pedrosa-Harand A. , Houben A.
Published: July 2020

For a long time, the Cyperid clade (Thurniceae-Juncaceae-Cyperaceae) was considered as a group of species possessing holocentromeres exclusively. The basal phylogenetic position ofPrionium serratumL. f. Drège (Thurniceae) within Cyperids makes this species an important specimen to understand the centromere evolution within this clade. Unlike expected, the chromosomal distribution of the centromere-specific histone H3 (CENH3), alpha-tubulin and different centromere associated post-translational histone modifications (H3S10ph, H3S28ph and H2AT120ph) demonstrate a monocentromeric organisation ofP. serratumchromosomes. Analysis of the high-copy repeat composition resulted in the identification of a centromere-localised satellite repeat. Hence, monocentricity was the ancestral condition for the Juncaceae-Cyperaceae-Thurniaceae Cyperid clade and holocentricity in this clade has independently arisen at least twice after differentiation of the three families, once in Juncaceae and the other one in Cyperaceae. Methods suitable for the identification of holocentromeres are discussed.
ElevatedMCOLN1Expression in p53-Deficient Bladder Cancer is Necessary for Oncogene-Induced Cell proliferation, Inflammation, and Invasion
Authors: Jung Jewon , Liao Han , Liang Hong , Hancock John F. , Denicourt Catherine , Venkatachalam Kartik
Published: July 2020

Inhibition of the endolysosomal cation channel, TRPML1, which is encoded byMCOLN1, deters the proliferation of cancer cells with augmented TFEB activity. Here, we report that the tumor suppressor, p53, antagonizes TFEB-drivenMCOLN1expression in bladder cancer. Not only was the constitutive loss of p53 in bladder cancer cells associated with higherMCOLN1mRNA, knockdown ofTP53in lines with wild type alleles of the tumor suppressor increasedMCOLN1expression. Elevated TRPML1 abundance in p53-deficient cancer cells, although not sufficient for bolstering proliferation, was necessary for the effects of oncogenic HRAS on cell division, cytokine production, and invasion. These data demonstrate that hyperactivation of the TFEB–MCOLN1transcriptional axis in urothelial cells lacking p53 permits tumorigenesis stemming fromHRASmutations. Furthermore, the insight that loss of p53 predicts addiction to TRPML1 informs an actionable therapeutic strategy for bladder cancer.
Disproportionate incidence of COVID-19 in African Americans correlates with dynamic segregation
Authors: Bassolas Aleix , Sousa Sandro , Nicosia Vincenzo
Published: July 2020

Socio-economic disparities quite often have a central role in the unfolding of large-scale catastrophic events. One of the most concerning aspects of the ongoing COVID-19 pandemics [1] is that it disproportionately affects people from Black and African American backgrounds [2–6], creating an unexpected infection gap. Interestingly, the abnormal impact on these ethnic groups seem to be almost uncorrelated with other risk factors, including co-morbidity, poverty, level of education, access to healthcare, residential segregation, and response to cures [7–11]. A proposed explanation for the observed incidence gap is that people from African American backgrounds are more often employed in low-income service jobs, and are thus more exposed to infection through face-to-face contacts [12], but the lack of direct data has not allowed to draw strong conclusions in this sense so far. Here we introduce the concept of dynamic segregation, that is the extent to which a given group of people is internally clustered or exposed to other groups, as a result of mobility and commuting habits. By analysing census and mobility data on more than 120 major US cities, we found that the dynamic segregation of African American communities is significantly associated with the weekly excess COVID-19 incidence and mortality in those communities. The results confirm that knowing where people commute to, rather than where they live, is much more relevant for disease modelling.
Socioeconomic, racial and ethnic differences in patient experience of clinician empathy: Results of a systematic review and meta-analysis
Authors: Roberts Brian W. , Puri Nitin K. , Trzeciak Christian J. , Mazzarelli Anthony J. , Trzeciak Stephen
Published: July 2020

Introduction

Empathy is essential for high quality health care. Health care disparities may reflect a systemic lack of empathy for disadvantaged people; however, few data exist on disparities in patient experience of empathy during face-to-face health care encounters with individual clinicians. We systematically analyzed the literature to test if socioeconomic status (SES) and race/ethnicity disparities exist in patient-reported experience of clinician empathy.

Methods

Using a published protocol, we searched Ovid MEDLINE, PubMed, CINAHL, EMBASE, CENTRAL and PsychINFO for studies using the Consultation and Relational Empathy (CARE) Measure, which to date is the most commonly used and well-validated methodology for measuring clinician empathy from the patient perspective. We included studies containing CARE Measure data stratified by SES and/or race/ethnicity. We contacted authors to request stratified data, when necessary. We performed quantitative meta-analyses using random effects models to test for empathy differences by SES and race/ethnicity.

Results

Eighteen studies (n=9,708 patients) were included. We found that, compared to patients whose SES was not low, low SES patients experienced lower empathy from clinicians (mean difference= -0.87 [95% confidence interval -1.72 to -0.02]). Compared to white patients, empathy scores were numerically lower for patients of multiple race/ethnicity groups (Black/African American, Asian, Native American, and all non-whites combined) but none of these differences reached statistical significance.

Conclusion

These data suggest an empathy gap may exist for patients with low SES. More research is needed to further test for SES and race/ethnicity disparities in clinician empathy and help promote health care equity.

Registration (PROSPERO)

CRD42019142809
Adolescents’ health literacy, health protective measures, and health-related quality of life during the Covid-19 pandemic
Authors: Riiser Kirsti , Helseth Sølvi , Haraldstad Kristin , Torbjørnsen Astrid , Richardsen Kåre Rønn
Published: July 2020

Purpose

First, to describe adolescents’ health information sources and knowledge, health literacy (HL), health protective measures, and health-related quality of life (HRQoL) during the initial phase of the Covid-19 pandemic in Norway. Second, to investigate the association between HL and the knowledge and behavior relevant for preventing spread of the virus. Third, to explore variables associated with HRQoL in a pandemic environment.

Methods

This cross-sectional study includes survey data from 2,205 Norwegian adolescents 16–19 years of age. The participants reported on their health information sources, HL, handwashing knowledge and behavior, number of social interactions, and HRQoL. Associations between study variables and specified outcomes were explored using multiple linear and logistic regression analyses.

Results

Television (TV) and family were indicated to be the main sources for pandemic-related health information. Handwashing, physical distancing, and limiting the number of social contacts were the most frequently reported measures. HL and handwashing knowledge and HL and handwashing behavior were significantly associated. For each unit increase on the HL scale, the participants were 5% more likely to socialize less with friends in comparison to normal. The mean HRQoL was very poor compared to European norms. Being quarantined or isolated and having confirmed or suspected Covid-19 were significantly negatively associated with HRQoL, but seeing less friends than normal was not associated. HL was significantly positively associated with HRQoL, albeit of minor clinical importance.

Conclusion

Adolescents follow the health authorities’ guidelines and appear highly literate. However, high fidelity requires great sacrifice because the required measures seem to collide with certain aspects that are important for the adolescents’ HRQoL.

Implications and contribution

This study is among the first to investigate health information sources and knowledge, health literacy, protective measures, and health-related quality of life (HRQoL) among adolescents during the Covid-19 pandemic. It identifies that the participating adolescents have high health literacy and knowledge about preventing the spread of the virus but that, at the same time, their HRQoL is poor.
Approximate relationships between SIR and logistic models
Authors: Clark David E. , Welch Gavin , Peck Jordan S.
Published: July 2020

Infectious epidemics are often described using a three-compartment Susceptible-Infectious-Removed (SIR) model, whose solution can be shown to involve generalizations of the logistic distribution. Using mathematical relationships relating these generalized logistic distributions, the population proportion remaining Susceptible can be approximated using the inverse of a standard cumulative logistic distribution, while the population proportion actively Infectious can be approximated using the density of a logistic or log-logistic distribution. Conversely, the parameters of an underlying SIR model can be approximately inferred from population-based data that have been estimated using logistic and/or log-logistic models.
SARS-CoV-2 Seroprevalence Among Parturient Women
Authors: Flannery Dustin D. , Gouma Sigrid , Dhudasia Miren B. , Mukhopadhyay Sagori , Pfeifer Madeline R. , Woodford Emily C. , Gerber Jeffrey S. , Arevalo Claudia P. , Bolton Marcus J. , Weirick Madison E. , Goodwin Eileen C. , Anderson Elizabeth M. , Greenplate Allison R. , Kim Justin , Han Nicholas , Pattekar Ajinkya , Dougherty Jeanette , Kuthuru Oliva , Mathew Divij , Baxter Amy E. , Vella Laura A. , Weaver JoEllen , Verma Anurag , Leite Rita , Morris Jeffrey S. , Rader Daniel J. , Elovitz Michal A. , Wherry E. John , Puopolo Karen M. , Hensley Scott E.
Published: July 2020

Limited data are available for pregnant women affected by SARS-CoV-2. Serological tests are critically important to determine exposure and immunity to SARS-CoV-2 within both individuals and populations. We completed SARS-CoV-2 serological testing of 1,293 parturient women at two centers in Philadelphia from April 4 to June 3, 2020. We tested 834 pre-pandemic samples collected in 2019 and 15 samples from COVID-19 recovered donors to validate our assay, which has a ∼1% false positive rate. We found 80/1,293 (6.2%) of parturient women possessed IgG and/or IgM SARS-CoV-2-specific antibodies. We found race/ethnicity differences in seroprevalence rates, with higher rates in Black/non-Hispanic and Hispanic/Latino women. Of the 72 seropositive women who also received nasopharyngeal polymerase chain reaction testing during pregnancy, 46 (64%) were positive. Continued serologic surveillance among pregnant women may inform perinatal clinical practices and can potentially be used to estimate seroprevalence within the community.

One Sentence Summary

Six percent of pregnant women delivering from April 4 to June 3, 2020 had serological evidence of exposure to SARS-CoV-2 with notable race/ethnicity differences in seroprevalence rates.
Dual nature of human ACE2 glycosylation in binding to SARS-CoV-2 spike
Authors: Mehdipour Ahmad Reza , Hummer Gerhard
Published: July 2020

Binding of the spike protein of SARS-CoV-2 to the human angiotensin converting enzyme 2 (ACE2) receptor triggers translocation of the virus into cells. Both the ACE2 receptor and the spike protein are heavily glycosylated, including at sites near their binding interface. We built fully glycosylated models of the ACE2 receptor bound to the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Using atomistic molecular dynamics (MD) simulations, we found that the glycosylation of the human ACE2 receptor contributes substantially to the binding of the virus. Interestingly, the glycans at two glycosylation sites, N90 and N322, have opposite effects on spike protein binding. The glycan at the N90 site partly covers the binding interface of the spike RBD. Therefore, this glycan can interfere with the binding of the spike protein and protect against docking of the virus to the cell. By contrast, the glycan at the N322 site interacts tightly with the RBD of the ACE2-bound spike protein and strengthens the complex. Remarkably, the N322 glycan binds into a conserved region of the spike protein identified previously as a cryptic epitope for a neutralizing antibody. By mapping the glycan binding sites, our MD simulations aid in the targeted development of neutralizing antibodies and SARS-CoV-2 fusion inhibitors.
WormPose: Image synthesis and convolutional networks for pose estimation inC. elegans
Authors: Hebert Laetitia , Ahamed Tosif , Costa Antonio C. , O’Shaugnessy Liam , Stephens Greg J.
Published: July 2020

An important model system for understanding genes, neurons and behavior, the nematode wormC. elegansnaturally moves through a variety of complex postures, for which estimation from video data is challenging. We introduce an open-source Python package, WormPose, for 2D pose estimation inC. elegans, including self-occluded, coiled shapes. We leverage advances in machine vision afforded from convolutional neural networks and introduce a synthetic yet realistic generative model for images of worm posture, thus avoiding the need for human-labeled training. WormPose is effective and adaptable for imaging conditions across worm tracking efforts. We quantify pose estimation using synthetic data as well as N2 and mutant worms in on-food conditions. We further demonstrate WormPose by analyzing long (∼ 10 hour), fast-sampled (∼ 30 Hz) recordings of on-food N2 worms to provide a posture-scale analysis of roaming/dwelling behaviors.
Effects of pharmacological calcimimetics on colorectal cancer cells over-expressing the human calcium-sensing receptor
Authors: Iamartino Luca , Elajnaf Taha , Gall Katharina , David Jacquelina , Manhardt Teresa , Heffeter Petra , Grusch Michael , Derdak Sophia , Baumgartner-Parzer Sabina , Schepelmann Martin , Kallay Enikö
Published: July 2020

The calcium-sensing receptor (CaSR) is a ubiquitously expressed multifunctional G protein-coupled receptor. Several studies reported that the CaSR plays an anti-inflammatory and anti-tumorigenic role in the intestine, and that it is down-regulated during colorectal carcinogenesis. We hypothesized that intestine-specific positive allosteric CaSR modulators (type II calcimimetics) could be used for the treatment of intestinal pathologies. Therefore, the aim of this study was to determine the effect of pharmacological stimulation of CaSR on gene expressionin vitroand on tumor growthin vivo.

We stably transduced two colon cancer cell lines (HT29 and Caco2) with lentiviral vectors containing either theCaSRfused to GFP or GFP only. Using RNA sequencing, RT-qPCR experiments and ELISA, we determined that CaSR over-expression itself had generally little effect on gene expression in these cells. However, treatment with 1μM of the calcimimetic NPS R-568 increased the expression of pro-inflammatory factors such as IL-23α and IL-8 and reduced the transcription of various differentiation markers in the cells over-expressing the CaSR.In vivo, neither the presence of the CaSR norp.o. treatment of the animals with the calcimimetic cinacalcet affected tumor growth, tumor cell proliferation or tumor vascularization of murine HT29 xenografts.

In summary, CaSR stimulation in CaSR over-expressing cells enhanced the expression of inflammatory markersin vitro, but was not able to repress colorectal cancer tumorigenicityin vivo. These findings suggest potential pro-inflammatory effects of the CaSR and type II calcimimetics in the intestine.
Type V Myosin focuses the polarisome and shapes the tip of yeast cells
Authors: Dünkler Alexander , Leda Marcin , Kromer Jan-Michael , Neller Joachim , Gronemeyer Thomas , Goryachev Andrew B. , Johnsson Nils
Published: July 2020

The polarisome is a cortical proteinaceous micro-compartment that organizes the growth of actin filaments and the fusion of secretory vesicles in yeasts and filamentous fungi. Polarisomes are compact, spot-like structures at the growing tips of their respective cells. The molecular forces that control form and size of this micro-compartment are not known. Here we identify a complex between the polarisome subunit Pea2 and the type V Myosin Myo2 that anchors Myo2 at the cortex of yeast cells. We discovered a point mutation in the cargo-binding domain of Myo2 that impairs the interaction with Pea2 and consequently the formation and focused localization of the polarisome. Cells carrying this mutation grow round instead of elongated buds. Further experiments and biophysical modeling suggest that polarisome nanoparticles use multiple copies of Myo2 and an actin filament polymerizing activity to drive the assembly of the polarisome and sustain its compact shape.
An improved 3DMax algorithm to reconstruct the three-dimensional structure of the chromosome
Authors: Liu Liwei , Yao Huili
Published: July 2020

In recent years, with the development of high-throughput chromosome conformation capture (Hi-C) technology and the reduction of high-throughput sequencing cost, the data volume of whole-genome interaction has increased rapidly, and the resolution of interaction map keeps improving. Great progress has been made in the research of 3D structure modeling of chromosomes and genomes. Several methods have been proposed to construct the chromosome structure from chromosome conformation capture data. Based on the Hi-C data, this paper analyses the relevant literature of chromosome 3D structure reconstruction and it summarizes the principle of 3DMAX, which is a classical algorithm to construct the 3D structure of a chromosome. In this paper, we introduce a new gradient ascent optimization algorithm called XNadam that is a variant of Nadam optimization method. When XNadam is applied to 3DMax algorithm, the performance of 3DMax algorithm can be improved, which can be used to predict the three-dimensional structure of a chromosome.

Author summary

The exploration of the three-dimensional structure of chromosomes has gradually become a necessary means to understand the relationship between genome function and gene regulation. An important problem in the construction of three-dimensional model is how to use the interaction map. Usually, the interaction frequency can be transformed into the spatial distance according to the deterministic or non-deterministic function relationship, and the interaction frequency can be weighted as weight in the objective function of the optimization problem. When the frequency of interaction is weighted as weight in the objective function of the optimization problem, what kind of optimization method is used to optimize the objective function is the problem we consider. In order to solve this problem, we provide an improved stochastic gradient ascent optimization algorithm(XNadam). The XNadam optimization algorithm combined with maximum likelihood algorithm is applied to high resolution Hi-C data set to infer 3D chromosome structure.
IL-33 expression in response to SARS-CoV-2 correlates with seropositivity in COVID-19 convalescent individuals
Authors: Stanczak Michal A. , Sanin David E. , Apostolova Petya , Nerz Gabriele , Lampaki Dimitrios , Hofmann Maike , Steinmann Daniel , Thimme Robert , Mittler Gerhard , Waller Cornelius F. , Pearce Edward J. , Pearce Erika L.
Published: July 2020

Our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still developing. We investigated seroprevalence and immune responses in subjects professionally exposed to SARS-CoV-2 and their family members (155 individuals; ages 5–79 years). Seropositivity for SARS-CoV-2 spike glycoprotein aligned with PCR results that confirmed previous infection. Anti-spike IgG titers remained high 60 days post-infection and did not associate with symptoms, but spike-specific IgM did associate with malaise and fever. We found limited household transmission, with children of infected individuals seldomly seropositive, highlighting professional exposure as the dominant route of infection in our cohort. We analyzed PBMCs from a subset of seropositive and seronegative adults. TLR7 agonist-activation revealed an increased population of IL-6+TNF-IL-1β+ monocytes, while SARS-CoV-2 peptide stimulation elicited IL-33, IL-6, IFNa2, and IL-23 expression in seropositive individuals. IL-33 correlated with CD4+ T cell activation in PBMCs from convalescent subjects, and was likely due to T cell-mediated effects on IL-33-producing cells. IL-33 is associated with pulmonary infection and chronic diseases like asthma and COPD, but its role in COVID-19 is unknown. Analysis of published scRNAseq data of bronchoalveolar lavage fluid (BALF) from patients with mild to severe COVID-19 revealed a population of IL-33-producing cells that increases with disease. Together these findings show that IL-33 production is linked to SARS-CoV-2 infection and warrant further investigation of IL-33 in COVID-19 pathogenesis and immunity.