bluuebunny/crossref_metadata_2025 huggingface dataset:
Middleware for providing activity-driven assistance in cyber-physical production systems☆
Authors: Dhiman Hitesh , Röcker Carsten
Published: November 2020

Assistance is becoming increasingly relevant in carrying out industrial work in the context of cyber-physical production systems (CPPSs) and Industry 4.0. While assistance in a single task via a single interaction modality has been explored previously, crossdevice interaction could improve the quality of assistance, especially given the concurrent and distributed nature of work in CPPSs. In this paper, we present the theoretical foundations and implementation of MiWSICx (Middleware for Work Support in Industrial Contexts), a middleware that showcases how multiple interactive computing devices such as tablets, smartphones, augmented/virtual reality glasses, and wearables could be combined to provide crossdevice industrial assistance. Based on activity theory, MiWSICx models human work as activities combining multiple users, artifacts, and cyber-physical objects. MiWSICx is developed using the actor model for deployment on a variety of hardware alongside a CPPS to provide multiuser, crossdevice, multiactivity assistance.
Social Security, Labor Supply, and Health of Older Workers: Quasi-Experimental Evidence from a Large Reform
Authors: Saporta-Eksten Itay , Shurtz Ity , Weisburd Sarit
Published: November 2020

We study the effects of public pension systems on the retirement timing of older workers and, in turn, the health consequences of delaying retirement by those workers. Causal inference relies on a social security reform in Israel that shifted payments from husbands to their (nonworking) wives, thereby substantially reducing the implied tax on the husband's employment while keeping overall household wealth constant. Using administrative social security data, we estimate extensive-margin labor supply elasticities with respect to the average net-of-tax rate of about 0.43 for men over 65. Using the reform to instrument for employment, we find that working an additional full year at old age decreases longevity. This mortality effect occurs after age 75 and is driven by workers holding blue-collar jobs. Finally, we evaluate the effect of the reform on earnings. The results imply a small value for an additional year of life, suggesting that workers underestimate the health cost of employment at older ages. (JEL: J10, J26, J22, H31)
SARS-CoV-2 spike protein binds to bacterial lipopolysaccharide and boosts proinflammatory activity
Authors: Petruk Ganna , Puthia Manoj , Petrlova Jitka , Samsudin Firdaus , Strömdahl Ann-Charlotte , Cerps Samuel , Uller Lena , Kjellström Sven , Bond Peter J , Schmidtchen and Artur
Published: November 2020

There is a link between high lipopolysaccharide (LPS) levels in the blood and the metabolic syndrome, and metabolic syndrome predisposes patients to severe COVID-19. Here, we define an interaction between SARS-CoV-2 spike (S) protein and LPS, leading to aggravated inflammation in vitro and in vivo. Native gel electrophoresis demonstrated that SARS-CoV-2 S protein binds to LPS. Microscale thermophoresis yielded a KD of ∼47 nM for the interaction. Computational modeling and all-atom molecular dynamics simulations further substantiated the experimental results, identifying a main LPS-binding site in SARS-CoV-2 S protein. S protein, when combined with low levels of LPS, boosted nuclear factor-kappa B (NF-κB) activation in monocytic THP-1 cells and cytokine responses in human blood and peripheral blood mononuclear cells, respectively. The in vitro inflammatory response was further validated by employing NF-κB reporter mice and in vivo bioimaging. Dynamic light scattering, transmission electron microscopy, and LPS-FITC analyses demonstrated that S protein modulated the aggregation state of LPS, providing a molecular explanation for the observed boosting effect. Taken together, our results provide an interesting molecular link between excessive inflammation during infection with SARS-CoV-2 and comorbidities involving increased levels of bacterial endotoxins.
Impact of Infectious Diseases Consultation on Management and Outcome ofStaphylococcus aureusBacteremia in Children
Authors: Duguid Robert C , Al Reesi Mohammed , Bartlett Adam W , Palasanthiran Pamela , McMullan Brendan J
Published: November 2020

Background

To examine the impact of infectious diseases consultation (IDC) on the management and outcome of Staphylococcus aureus bacteremia (SAB) in children.

Methods

A retrospective cohort study of children with SAB at a teritary pediatric hospital (January 2009-June 2015) identified by medical record review as to whether they received an IDC for SAB at the discretion of the admitting physician or surgeon was conducted. Differences in management and outcomes for those with and without IDC were evaluated, and multivariate regression analysis was used to determine factors associated with cure.

Results

There were 100 patients included in the analysis. Fifty-five patients received IDC and 45 had no IDC (NIDC). Appropriate directed therapy within 24 hours (54/55 = 98.2% vs 34/45 = 75.6%, P < .01), choice (54/55 = 98.2% vs 37/45 = 82.2%, P < .01), dose (54/55 = 98.2% vs 36/45 = 80%, P < .01), and duration (52/55 = 94.5% vs 24/45 = 53.3%, P < .01) of directed antibiotic therapy were appropriate in more IDC group patients. Achievement of source control in indicated cases was also more common in the IDC group (28/32 = 87.5% vs 5/26 = 19.1%, P < .01). Appropriate investigation with repeat blood cultures and echocardiograms was not significantly different. All 55 patients in the IDC group had a complete response (cure) compared with 40 of the 45 (88.9%) patients in the NIDC group: 2 patients died and 3 patients had a relapse of infection with subsequent cure. In multivariate regression analysis, methicillin-susceptible SAB and IDC were factors independently associated with cure.

Conclusions

Children who received IDC for SAB in a tertiary pediatric setting were more likely to have appropriate investigations and management and had improved outcomes.
Acute appendicitis as an unusual cause of invasive ductal breast carcinoma metastasis
Authors: De Pauw Vincent , Navez Julie , Holbrechts Stephane , Lemaitre Jean
Published: November 2020

Acute appendicitis is one of the most common causes of abdominal pain at the emergency room. In rare cases, it can be caused by malignancy, even metastatic lesions from extra-abdominal neoplasia. Herein, we report a case of a 64-year-old female with a history of invasive ductal carcinoma of the breast treated by chemotherapy, surgery, radiotherapy and hormonotherapy, relapsing several years later as a bone and a pleura metastasis successfully cured by locoregional therapy and hormonal treatment. She presented with acute abdominal pain without signs of peritonitis. Abdominal computed tomodensitometry showed sign of appendicitis. Therefore, laparoscopic exploration and appendicectomy was performed. During surgery, multiple peritoneal nodules were found and harvested. Pathology showed metastatic nodules of invasive ductal breast carcinoma, including in the appendicular wall, concluding to peritoneal carcinomatosis. The postoperative course was uneventful, but the patient died 1 year later after refusing anticancer treatment.
Intestinal ischemia in a COVID-19 patient: case report from Northern Tanzania
Authors: Kiwango Frank , Mremi Alex , Masenga Albert , Akrabi Huda
Published: November 2020

Novel coronavirus disease 2019 (COVID-19) was first identified in Wuhan, China, and declared by World Health Organization as a pandemic in March 2020. Since then, it has been well known for COVID-19 patients to present with clinical manifestations of severe acute respiratory syndrome (SARS-CoV-2) similar to the influenza. However, in the course of the disease, various pathological complications of high clinical significance have remained unknown. Impaired blood supply to the visceral vascular system can cause serious life-threatening acute damage. We report a case of a 60-year-old female with difficulty in breathing and extensive acute intestinal ischemia confirmed to be associated with SARS-CoV-2 infection. The patient developed a sudden abdominal pain and succumbed shortly after admission before imaging studies were performed. Autopsy revealed massive bowel ischemia. This case highlights the importance of paying attention to serious and less known clinical manifestations other than pulmonary symptoms and fever.
Inferring (sub)millimetre dust opacities and temperature structure in edge-on protostellar discs from resolved multiwavelength continuum observations: the case of the HH 212 disc
Authors: Lin Zhe-Yu Daniel , Lee Chin-Fei , Li Zhi-Yun , Tobin John J , Turner Neal J
Published: November 2020

(Sub)millimetre dust opacities are required for converting the observable dust continuum emission to the mass, but their values have long been uncertain, especially in discs around young stellar objects. We propose a method to constrain the opacity κν in edge-on discs from a characteristic optical depth τ0,ν, the density ρ0, and radius R0 at the disc outer edge through κν = τ0,ν/(ρ0R0), where τ0,ν is inferred from the shape of the observed flux along the major axis, ρ0 from gravitational stability considerations, and R0 from direct imaging. We applied the 1D semi-analytical model to the embedded, Class 0, HH 212 disc, which has high-resolution data in Atacama Large Millimetre/submillimetre Array (ALMA) bands 9, 7, 6, and 3 and Very Large Array Ka band (λ = 0.43, 0.85, 1.3, 2.9, and 9.1 mm). The modelling is extended to 2D through RADMC-3D radiative transfer calculations. We find a dust opacity of κν ≈ 1.9 × 10−2, 1.3 × 10−2, and 4.9 × 10−3 cm2 g−1 of gas and dust for ALMA bands 7, 6, and 3, respectively, with uncertainties dependent on the adopted stellar mass. The inferred opacities lend support to the widely used prescription κλ = 2.3 × 10−2(1.3mm/λ) cm2 g−1 . We inferred a temperature of ∼45 K at the disc outer edge that increases radially inwards. It is well above the sublimation temperatures of ices such as CO and N2, which supports the notion that the disc chemistry cannot be completely inherited from the protostellar envelope.
Flux-density measurements of the high-redshift blazar PSO J047.4478+27.2992 at 4.7 and 8.2 GHz with RATAN-600
Authors: Mufakharov T , Mikhailov A , Sotnikova Yu , Mingaliev M , Stolyarov V , Erkenov A , Nizhelskij N , Tsybulev P
Published: November 2020

We report the first detection at 4.7 and 8.2 GHz with the RATAN-600 radio telescope of the source PSO J047.4478+27.2992, which has been announced as a blazar at z = 6.1. The average flux densities are 12 ± 3 and 8 ± 4 mJy at 4.7 and 8.2 GHz respectively, and an upper limit is estimated as 3 mJy at 11.2 GHz. The light curve at 4.7 GHz, obtained on a time-scale of four months, exhibits moderate variability of the source (fractional variability Fvar = 0.28 ± 0.02). The new RATAN-600 measurements extend previous literature data to higher frequencies, indicating a single power-law radio spectrum with α0.147–8.2 = −0.51 ± 0.1. The monochromatic radio luminosity at 4.7 GHz Pν ∼ 2 × 1027 W Hz−1 is consistent with values for high-redshift quasars at z ≥ 3.
Postacute Cognitive Rehabilitation for Adult Brain Tumor Patients
Authors: Weyer-Jamora Christina , Brie Melissa S , Luks Tracy L , Smith Ellen M , Hervey-Jumper Shawn L , Taylor Jennie W
Published: November 2020

Intrinsic brain tumors often occur within functional neural networks, leading to neurological impairment and disability of varying degrees. Advances in our understanding of tumor-network integration, human cognition and language processing, and multiparametric imaging, combined with refined intraoperative tumor resection techniques, have enhanced surgical management of intrinsic brain tumors within eloquent areas. However, cognitive symptoms impacting health-related quality of life, particularly processing speed, attention, concentration, working memory, and executive function, often persist after the postoperative recovery period and treatment. Multidisciplinary cognitive rehabilitation is the standard of care for addressing cognitive impairments in many neurological diseases. There is promising research to support the use of cognitive rehabilitation in adult brain tumor patients. In this review, we summarize the history and usefulness of postacute cognitive rehabilitation for adult brain tumor patients.
IIB matrix model: Emergent spacetime from the master field
Authors: Klinkhamer F R
Published: November 2020

We argue that the large-$N$ master field of the Lorentzian IIB matrix model can give the points and metric of a classical spacetime.
Evaluating a child care-based social marketing approach for improving children’s diet and physical activity: results from the Healthy Me, Healthy We cluster-randomized controlled trial
Authors: Vaughn Amber E , Hennink-Kaminski Heidi , Moore Renee , Burney Regan , Chittams Jesse L , Parker Portia , Luecking Courtney T , Hales Derek , Ward Dianne S
Published: November 2020

Child care-based interventions offer an opportunity to reach children at a young and impressionable age to support healthy eating and physical activity behaviors. Ideally, these interventions engage caregivers, including both childcare providers and parents, in united effort. This study evaluated the impact of the Healthy Me, Healthy We intervention on children’s diet quality and physical activity. A sample of 853 three- to four-year-old children from 92 childcare centers were enrolled in this cluster-randomized control trial. Healthy Me, Healthy We was an 8-month, social marketing intervention delivered through childcare that encouraged caregivers (childcare providers and parents) to use practices that supported children’s healthy eating and physical activity behaviors. Outcome measures, collected at baseline and post-intervention, assessed children’s diet quality, physical activity, and BMI as well as caregivers’ feeding and physical activity practices. Generalized Linear Mixed Models were used to assess change from baseline to post-intervention between intervention and control arms. No significant changes were noted in any of the outcome measures except for small improvements in children’s sodium intake and select parent practices. Despite the negative findings, this study offers many lessons about the importance and challenges of effective parent engagement which is critical for meaningful changes in children’s health behaviors.
The Modular Organization of Pain Brain Networks: An fMRI Graph Analysis Informed by Intracranial EEG
Authors: Fauchon Camille , Meunier David , Faillenot Isabelle , Pomares Florence B , Bastuji Hélène , Garcia-Larrea Luis , Peyron Roland
Published: November 2020

Intracranial EEG (iEEG) studies have suggested that the conscious perception of pain builds up from successive contributions of brain networks in less than 1 s. However, the functional organization of cortico-subcortical connections at the multisecond time scale, and its accordance with iEEG models, remains unknown. Here, we used graph theory with modular analysis of fMRI data from 60 healthy participants experiencing noxious heat stimuli, of whom 36 also received audio stimulation. Brain connectivity during pain was organized in four modules matching those identified through iEEG, namely: 1) sensorimotor (SM), 2) medial fronto-cingulo-parietal (default mode-like), 3) posterior parietal-latero-frontal (central executive-like), and 4) amygdalo-hippocampal (limbic). Intrinsic overlaps existed between the pain and audio conditions in high-order areas, but also pain-specific higher small-worldness and connectivity within the sensorimotor module. Neocortical modules were interrelated via “connector hubs” in dorsolateral frontal, posterior parietal, and anterior insular cortices, the antero-insular connector being most predominant during pain. These findings provide a mechanistic picture of the brain networks architecture and support fractal-like similarities between the micro-and macrotemporal dynamics associated with pain. The anterior insula appears to play an essential role in information integration, possibly by determining priorities for the processing of information and subsequent entrance into other points of the brain connectome.
Poor Head Growth Is Associated with Later Mental Delay among Vietnamese Preterm Infants: A Follow-up Study
Authors: Do Chuong Huu Thieu , Børresen Malene Landbo , Pedersen Freddy Karup , Nguyen Tinh Thu , Nguyen Hung Thanh , Kruse Alexandra Yasmin
Published: November 2020

Background

Preterm infants in low- and middle-income countries are at high risk of poor physical growth, but their growth data are still scarce.

Objectives

To describe the growth of Vietnamese preterm infants in the first 2 years, and to compare with references: World Health Organization (WHO) child growth standards, and healthy Southeast Asian (SEA) infants. Further, to assess the association between growth in the first year and neurodevelopment at 2 years corrected age (CA).

Methods

We conducted a cohort study to follow up preterm infants discharged from a neonatal intensive care unit for 2 years. Weight, length and head circumference (HC) were measured at 3, 12 and 24 months CA. Neurodevelopment was assessed using Bayley Scales of Infant and Toddler Development—3rd Edition at 24 months CA.

Results

Over 90% of the cohort showed catch-up weight at 3 months CA. Weight and length were comparable to healthy SEA but were lower than WHO standards. HC was significantly smaller than those of WHO standards with HC Z-scores steadily decreasing from −0.95 at 3 months CA to −1.50 at 24 months CA. Each one decrement of HC Z-score from 3 to 12 months CA was associated with nearly twice an increase in odds of mental delay at 24 months CA (odds ratio 1.89; 95% confidence interval 1.02–3.50).

Conclusion

Vietnamese preterm infants exhibited early catch-up weight but poor head growth, which was associated with later delays in mental development. Our findings support the importance of HC measures in follow-up for preterm infants.
Revitalizing Graduate Medical Education in Global Settings: Lessons From Post-Earthquake Haiti
Authors: Morse Michelle , Spahn Lauren , Pierre Paul , Lucien Franciscka , Israel Kerling , Toussaint Sterman , Robert Merly , Katz Joel T. , Buyske Jo , Clisbee Mary , Suffrin Dimitri J.C. , Raymonville Maxi , Cadet Jean Claude , Pierre Sosthene , Mukherjee Joia , Rhatigan Joseph , Farmer Paul E.
Published: November 2020

Following the massive 7.0-magnitude earthquake that devastated much of the Haitian capital city of Port-au-Prince on January 12, 2010, the Haitian health system and its medical education programs were fragmented, fragile, and facing a significant, overwhelming demand for clinical care. In response, the authors of this paper and the institutions they represent supported the development of a teaching hospital that could fill the void in academic training capacity while prioritizing the health of Haiti’s rural poor—goals aligned with the Haitian Ministry of Health (MOH) strategy. This bold initiative aimed to address both the immediate and long-term health care needs within post-disaster Haiti through a strategic investment in graduate medical education (GME). Here, the authors describe their approach, which included building consensus, aspiring to international standards, and investing in shared governance structures under Haitian leadership. The Haitian MOH strategy and priorities guided the development, implementation, and expansion of solutions to the ongoing crisis in human resources for health within the acute context. Local leadership of this initiative ensured a sustained and transformative model of GME that has carried Haiti beyond acute relief and toward a more reliable health system. The enduring success can be measured through sustained governance systems, graduates who have remained in Haiti, standardized curricula, a culture of continuous improvement, and the historic achievement of international accreditation. While ongoing challenges persist, Haiti has demonstrated that the strategy of investing in GME in response to acute disasters should be considered in other global settings to support the revitalization of tenuous health systems.
Brusatol reverses lipopolysaccharide-induced epithelial-mesenchymal transformation and induces apoptosis through PI3K/Akt/NF-кB pathway in human gastric cancer SGC-7901 cells
Authors: Chen Hejuntao , Jiang Ting , Chen Hui , Su Jingjing , Wang Xuncui , Cao Yin , Li Qinglin
Published: November 2020

Brusatol is a butyrolactone compound isolated from traditional Chinese medicine Brucea javanica. It has been reported to possess strong cytotoxicity against various cancer cells, thus showing its potential as an anticancer drug. Besides, lipopolysaccharide (LPS) plays a central role in the tumor microenvironment, while epithelial-mesenchymal transformation (EMT), a biological process by which epithelial cells are transformed into mesenchymal phenotypic cells through specific procedures, participates in chronic inflammation and tumor metastasis. This study aimed to investigate the inhibition of LPS-induced tumor cell invasion and metastasis and the molecular mechanism of apoptosis induced by brusatol in human gastric cancer SGC-7901 cells. Cell viability, cell migration and invasion ability, inflammatory factor release, and protein expression were detected using methyl thiazolyl tetrazolium assays, transwell assays, ELISA kit, and Western blot analysis, respectively. The change of EMT marker protein vimentin was assessed using immunofluorescence, while the apoptosis rate was measured using flow cytometry. In summary, brusatol inhibited LPS-induced EMT via the deactivation of the PI3K/Akt/NF-кB signaling pathway. This provides a useful new theoretical basis for the treatment of gastric cancer in the future.
Audiovisual Modules to Enhance Informed Consent in the ICU: A Pilot Study
Authors: Loftus Tyler J. , Alfaro Maria E. , Anderson Tiffany N. , Murphy Travis W. , Zayko Olga , Davis John P. , Hothem Zachary A. , Darden Dijoia B. , Patel Rohit P. , Whittet Wanda , McGough Edward K. , Bihorac Azra , Croft Chasen A. , Rosenthal Martin D. , Smith R. Stephen , Vanzant Erin L. , Moore Fredrick A. , Brakenridge Scott C. , Ghita Gabriela L. , Brumback Babette A. , Mohr Alicia M. , Efron Philip A.
Published: November 2020

Objectives:

Obtaining informed consent for commonly performed ICU procedures is often compromised by variability in communication styles and inadequate verbal descriptions of anatomic concepts. The objective of this study was to evaluate the efficacy of an audiovisual module in improving the baseline knowledge of ICU procedures among patients and their caregivers.

Design:

Prospective, observational study.

Setting:

Forty-eight–bed adult surgical ICU at a tertiary care center.

Subjects:

Critically ill surgical patients and their legally authorized representatives. .

Interventions:

An audiovisual module describing eight commonly performed ICU procedures.

Measurements and Main Results:

Fifty-nine subjects were enrolled and completed an 11-question pre- and postvideo test of knowledge regarding commonly performed ICU procedures and a brief satisfaction survey. Twenty-nine percent had a healthcare background. High school was the highest level of education for 37% percent of all subjects. Out of 11 questions on the ICU procedure knowledge test, subjects scored an average 8.0 ± 1.9 correct on the pretest and 8.4 ± 2.0 correct on the posttest (p = 0.055). On univariate logistic regression, having a healthcare background was a negative predictor of improved knowledge (odds ratio, 0.185; 95% CI, 0.045–0.765), indicating that those with a health background had a lower probability of improving their score on the posttest. Among subjects who did not have a healthcare background, scores increased from 7.7 ± 1.9 to 8.3 ± 2.1 (p = 0.019). Seventy-five percent of all subjects indicated that the video was easy to understand, and 70% believed that the video improved their understanding of ICU procedures.

Conclusions:

Audiovisual modules may improve knowledge and comprehension of commonly performed ICU procedures among critically ill patients and caregivers who have no healthcare background.
Delirium Incidence, Duration, and Severity in Critically Ill Patients With Coronavirus Disease 2019
Authors: Khan Sikandar H. , Lindroth Heidi , Perkins Anthony J. , Jamil Yasser , Wang Sophia , Roberts Scott , Farber Mark , Rahman Omar , Gao Sujuan , Marcantonio Edward R. , Boustani Malaz , Machado Roberto , Khan Babar A.
Published: November 2020

Objectives:

To determine delirium occurrence rate, duration, and severity in patients admitted to the ICU with coronavirus disease 2019.

Design:

Retrospective data extraction study from March 1, 2020, to June 7, 2020. Delirium outcomes were assessed for up to the first 14 days in ICU.

Setting:

Two large, academic centers serving the state of Indiana.

Patients:

Consecutive patients admitted to the ICU with positive severe acute respiratory syndrome coronavirus 2 nasopharyngeal swab polymerase chain reaction test from March 1, 2020, to June 7, 2020, were included. Individuals younger than 18 years of age, without any delirium assessments, or without discharge disposition were excluded.

Measurements and Main Results:

Primary outcomes were delirium rates and duration, and the secondary outcome was delirium severity. Two-hundred sixty-eight consecutive patients were included in the analysis with a mean age of 58.4 years (sd, 15.6 yr), 40.3% were female, 44.4% African American, 20.7% Hispanic, and a median Acute Physiology and Chronic Health Evaluation II score of 18 (interquartile range, 13–25). Delirium without coma occurred in 29.1% of patients, delirium prior to coma in 27.9%, and delirium after coma in 23.1%. The first Confusion Assessment Method for the ICU assessment was positive for delirium in 61.9%. Hypoactive delirium was the most common subtype (87.4%). By day 14, the median number of delirium/coma-free were 5 days (interquartile range, 4–11 d), and median Confusion Assessment Method for the ICU-7 score was 6.5 (interquartile range, 5–7) indicating severe delirium. Benzodiazepines were ordered for 78.4% of patients in the cohort. Mechanical ventilation was associated with greater odds of developing delirium (odds ratio, 5.0; 95% CI, 1.1–22.2; p = 0.033) even after adjusting for sedative medications. There were no between-group differences in mortality.

Conclusions:

Delirium without coma occurred in 29.1% of patients admitted to the ICU. Delirium persisted for a median of 5 days and was severe. Mechanical ventilation was significantly associated with odds of delirium even after adjustment for sedatives. Clinical attention to manage delirium duration and severity, and deeper understanding of the virus’ neurologic effects is needed for patients with coronavirus disease 2019.
Reversal of the Pathophysiological Responses to Gram-Negative Sepsis by Megadose Vitamin C
Authors: Lankadeva Yugeesh R. , Peiris Rachel M. , Okazaki Nobuki , Birchall Ian E. , Trask-Marino Anton , Dornom Anthony , Vale Tom A. M. , Evans Roger G. , Yanase Fumitaka , Bellomo Rinaldo , May Clive N.
Published: November 2020

Objectives:

Oxidative stress appears to initiate organ failure in sepsis, justifying treatment with antioxidants such as vitamin C at megadoses. We have therefore investigated the safety and efficacy of megadose sodium ascorbate in sepsis.

Design:

Interventional study.

Setting:

Research Institute.

Subjects:

Adult Merino ewes.

Interventions:

Sheep were instrumented with pulmonary and renal artery flow-probes, and laser-Doppler and oxygen-sensing probes in the kidney. Conscious sheep received an infusion of live Escherichia coli for 31 hours. At 23.5 hours of sepsis, sheep received fluid resuscitation (30 mL/kg, Hartmann solution) and were randomized to IV sodium ascorbate (0.5 g/kg over 0.5 hr + 0.5 g/kg/hr for 6.5 hr; n = 5) or vehicle (n = 5). Norepinephrine was titrated to restore mean arterial pressure to baseline values (~80 mm Hg).

Measurements and Main Results:

Sepsis-induced fever (41.4 ± 0.2°C; mean ± se), tachycardia (141 ± 2 beats/min), and a marked deterioration in clinical condition in all cases. Mean arterial pressure (86 ± 1 to 67 ± 2 mm Hg), arterial Po
2 (102.1 ± 3.3 to 80.5 ± 3.4 mm Hg), and renal medullary tissue Po
2 (41 ± 5 to 24 ± 2 mm Hg) decreased, and plasma creatinine doubled (71 ± 2 to 144 ± 15 µmol/L) (all p < 0.01). Direct observation indicated that in all animals, sodium ascorbate dramatically improved the clinical state, from malaise and lethargy to a responsive, alert state within 3 hours. Body temperature (39.3 ± 0.3°C), heart rate (99.7 ± 3 beats/min), and plasma creatinine (32.6 ± 5.8 µmol/L) all decreased. Arterial (96.5 ± 2.5 mm Hg) and renal medullary Po
2 (48 ± 5 mm Hg) increased. The norepinephrine dose was decreased, to zero in four of five sheep, whereas mean arterial pressure increased (to 83 ± 2 mm Hg). We confirmed these physiologic findings in a coronavirus disease 2019 patient with shock by compassionate use of 60 g of sodium ascorbate over 7 hours.

Conclusions:

IV megadose sodium ascorbate reversed the pathophysiological and behavioral responses to Gram-negative sepsis without adverse side effects. Clinical studies are required to determine if such a dose has similar benefits in septic patients.
Development of a Tetravalent T-Cell Engaging Bispecific Antibody Against Glypican-3 for Hepatocellular Carcinoma
Authors: Yu Lin , Huang Nan , Sun Heng , Yang Xi , Fu Yuna , Lang Qiaoli , Wang Jianhua , Ge Liangpeng
Published: November 2020

Cancer therapies benefit from accelerated development of biotechnology, and many immunotherapeutic strategies spring up including vaccines, the immune checkpoint blockade, chimeric antigen receptor T cells, and bispecific antibodies (BsAbs). Glypican-3 (GPC3) is a member of the heparan sulfate proteoglycan family of proteins and is highly expressed in hepatocellular carcinoma (HCC) cell membranes. Here, the authors describe a new tetravalent BsAb h8B-BsAb targeting GPC3 and CD3 antigens and studied its antitumor activities against HCC. h8B-BsAb was designed based on immunoglobulin G with a fragment variable fused to the light chain, whose biophysical stabilities including degradation resistance and thermostability were improved by introducing disulfide bonds. In vitro activity of h8B-BsAb showed potent T-cell recruitment and activation for HCC cell lysis by the presence of peripheral blood mononuclear cells, but no specific killing in GPC3-negative cells. In HCC xenograft mouse studies, h8B-BsAb induced robust regression of tumors. In summary, we engineered a highly stable and efficacious BsAb as a potential candidate for HCC treatment.
EARLY RETINAL MICROVASCULAR ABNORMALITIES IN YOUNG ADULTS WITH TYPE 1 DIABETES MELLITUS WITHOUT CLINICALLY EVIDENT DIABETIC RETINOPATHY
Authors: Chen Yun-Ju , Khouri Albert S. , Zarbin Marco A. , Szirth Bernard C.
Published: November 2020

Purpose:

To characterize the early retinal microvascular changes in young adults (age: 22.69 ± 3.50 years) with Type 1 diabetes mellitus without clinically detectable diabetic retinopathy using optical coherence tomography angiography and investigate the associated factors.

Methods:

A total of 36 participants with Type 1 diabetes mellitus (70 eyes) and 34 healthy controls (57 eyes) were retrospectively reviewed. The analyzed optical coherence tomography angiography indices included capillary vessel density, foveal avascular zone area/perimeter/acircularity index, and foveal vascular density, acquired in the 6 × 6-mm2 area centered on the fovea. The generalized estimation equations model was applied to compare the mean values and to study the associated factors.

Results:

In subjects with diabetes, statistically significant decreases were observed in parafoveal vessel density in both superficial and deep capillary plexuses, foveal avascular zone area/perimeter, and foveal vascular density when compared with controls (all P < 0.05). Higher glycated hemoglobin level was independently associated with the decrease of parafoveal vessel density as well as the increase of foveal avascular zone area/perimeter (all P < 0.05). Prepubescent onset of diabetes mellitus was also independently associated with the decrease of superficial parafoveal vessel density, foveal avascular zone area/perimeter, and foveal vascular density (P = 0.015, 0.011, 0.015, and 0.001, respectively).

Conclusion:

In young adults with Type 1 diabetes mellitus lacking clinical signs of diabetic retinopathy, optical coherence tomography angiography revealed alterations in retinal microvasculature that were associated with glycated hemoglobin level and onset of diabetes mellitus related to puberty.
Nutritional Composition and Health Benefits of Psyllium (Plantago ovata) Husk and Seed
Authors: Shah Aunjum Reyaz , Sharma Paras , Longvah Thingnganing , Gour Vinod Singh , Kothari S. L. , Shah Yasir Reyaz , Ganie Showkat Ahmad
Published: November 2020

Psyllium is an important medicinal plant cultivated in India, Pakistan, and Iran. The psyllium seed's husk is rich in arabinoxylans, and this component is used for treating certain gastrointestinal problems. It is also used as an ingredient in foods to improve their fiber content, texture, and rheological and sensory characteristics. Large doses of psyllium can give rise to flatulence and bloating. Also, in rare cases, psyllium husk can cause skin sensitivity and respiratory allergy in sensitive individuals after prolonged exposure.
Vulvar Pilomatrix Carcinoma: Morphologic and Molecular Features
Authors: Bueno Diego , Caniego-Casas Tamara , Sánchez-Martínez María Concepción , Saavedra-Serrano Cristina , Palacios José , Pérez-Mies Belén
Published: November 2020

Pilomatrix carcinoma (PC) is a rare malignant variant of pilomatrixoma, a skin adnexal tumor originating from hair matrix cells. It is most often located in the head, neck region, upper back and upper extremities. PC has a locally aggressive behavior but metastasis only occur in 10% of cases. Mutations in CTNNB1, the encoding gene of beta-catenin, have been found in both pilomatrixoma and PC, but other molecular alterations are unknown. The authors present a case of PC in the clitoris, the third known reported case located on the external genitalia. The tumor followed an unusual clinical course with the development of multiple metastases. Next-generation sequencing analysis of the tumor identified, in addition to a characteristic CTNNB1 mutation, pathogenic mutations in PTEN, PIK3CA, and ARID1A, which could explain the aggressive course of the disease. The diagnostic criteria of PC and the differential diagnoses of this unusual tumor in the genital area are discussed.
What Is Your Reality? Virtual, Augmented, and Mixed Reality in Plastic Surgery Training, Education, and Practice
Authors: Lee Gordon K. , Moshrefi Shawn , Fuertes Victor , Veeravagu Laksman , Nazerali Rahim , Lin Samuel J.
Published: November 2020

Virtual reality and other technological advancements both inside and outside the operating room have shown an exponential increase in the past two decades. Surgical technique and finesse in delicate procedures have become ever more important, and the onus is on plastic surgeons and plastic surgery residents to meet these needs to provide the best outcomes possible to patients. The ability to learn, simulate, and practice operating in a fashion that poses no harm to any patient is truly a gift from technology to surgery that any surgeon could benefit from, whether trainee or attending. This application of technology and simulation has been demonstrated in other fields such as in the airline industry with flight simulation. The ability to learn, synthesize, and incorporate learned materials and ideas through virtual, augmented, and mixed reality tools offers a great opportunity to put our field at the forefront of a paradigm shift in surgical education. The critical utility of digital education could not be further emphasized any more than in the unfortunate and infrequent situation of a worldwide pandemic. This article reviews some of the important recent technologies that have developed and their applications in plastic surgery education and offers a look into what we can expect in the future.
Caring for Family Caregivers: Perceptions of CARE Act Compliance and Implementation
Authors: Rodakowski Juleen , Leighton Cassandra , Martsolf Grant R. , James A. Everette
Published: November 2020

Background:

The Caregiver Advise, Record, Enable (CARE) Act encourages inclusion of family caregivers in the hospitalization process for patients. Translating the state laws into meaningful changes within the health care delivery system can be challenging and requires time. This study sought to examine early compliance with and implementation of the CARE Act reported by hospitals in the Commonwealth of Pennsylvania.

Methods:

We sent an online survey to hospital executives in Pennsylvania in 2017. Descriptive statistics were computed to examine hospital characteristics and used to assess compliance and implementation of the CARE Act tenets.

Results:

Most hospitals reported that changes have been and are being made to comply with the CARE Act (90.9%). Hospital executives reported that the family caregiver designation is available in 63.6% of the hospitals and notification of patient discharge is available in 45.5%. Hospital executives reported that family caregiver education and instruction is occurring in 31.8% of all inpatient stays. Hospital executives indicated that they are still developing processes to comply with the legislation and to integrate family caregivers into hospital systems and processes.

Conclusions:

Our findings suggest that hospitals are complying with the legislation, while fully operationalizing the components of the CARE Act is a work in progress.
Impact of County Health Rankings on Nationwide Liver Transplant Outcomes
Authors: Niazi Shehzad K. , Vargas Emily , Spaulding Aaron , Crook Julia , Keaveny Andrew P. , Schneekloth Terry , Rummans Teresa , Taner C. Burcin
Published: November 2020

Background.

There is limited information concerning whether social determinants of health affect postliver transplant (LT) outcomes. This study aims to understand to what extent the health of LT recipients’ counties of residence influence long-term LT outcomes.

Methods.

We used the United Network for Organ Sharing data to identify adult LT recipients transplanted between January 2010 and June 2018. Patient-level data were matched to county-level County Health Ranking (CHR) data using transplant recipient zip code, and nationwide CHRs were created. Mixed-effects Cox proportional hazards models were used to examine associations between CHRs and graft and patient survival post-LT.

Results.

Health outcomes rank was significantly associated with posttransplant graft and patient survival, with worst tertile counties showing a 13% increased hazard of both graft failure and patient mortality compared to the best tertile counties.

Conclusions.

Although county health is associated with LT outcomes, it also appears that LT recipient selection is effective at mitigating major disparities based on county of residence and helps yield equitable outcomes in this respect.
Neuroimaging Correlates of Lateralized Rhythmic Delta Activity, Lateralized Periodic Discharges, and Generalized Rhythmic Delta Activity on EEG in Critically Ill Patients
Authors: Alzawahmah Mohamed , Fong Michael W.K. , Gilmore Emily J. , Hirsch Lawrence J.
Published: November 2020

Purpose:

The neuroimaging correlates of lateralized rhythmic delta activity (LRDA) are not well defined, and imaging findings between different epileptiform patterns have seldom been compared directly.

Methods:

Patients were retrospectively selected from a critical care EEG database between December 2014 and December 2017. Patients were included if they had greater than 6 hours of continuous EEG that contained LRDA, lateralized periodic discharges LPDs), or generalized rhythmic delta activity (GRDA) and had an MRI within 48 hours of the EEG. Clinical, EEG, and MRI characteristics were collected and compared.

Results:

All the following results showed statistical significance between the groups: Patients with GRDA were more likely to have a normal MRI (LRDA, 0%; LPDs, 0.8%; GRDA, 17.3%), although the majority were abnormal. In patients with LRDA and LPDs, the MRI abnormalities were much more likely lateralized to one side, whereas in those with GRDA, they were more likely to have bilateral or multifocal abnormalities. Across all groups most abnormalities were acute, although this proportion was higher in patients with LRDA and LPDs compared with that in those with GRDA (LRDA, 91.3%; LPDs, 86.0%; GRDA, 70.4%). An MRI abnormality that was concordant with the side of LRDA was present in 66.3%, with 17.3% having discordant findings. These were similar in patients with LPDs (concordant 67.4%; discordant 11.6%).

Conclusions:

Patients with LRDA had a similarly high rate of acute focal abnormalities ipsilateral to the EEG pattern compared with those with LPDs. Patients with GRDA were more likely to have a normal MRI, but the majority of patients with GRDA still had acute focal findings.
Unravelling the distinct contribution of cell shape changes and cell intercalation to tissue morphogenesis: the case of the
Drosophila
trachea
Authors: Casani Sandra , Casanova Jordi , Llimargas Marta
Published: November 2020

Intercalation allows cells to exchange positions in a spatially oriented manner in an array of diverse processes, spanning convergent extension in embryonic gastrulation to the formation of tubular organs. However, given the co-occurrence of cell intercalation and changes in cell shape, it is sometimes difficult to ascertain their respective contribution to morphogenesis. A well-established model to analyse intercalation, particularly in tubular organs, is the
Drosophila
tracheal system. There, fibroblast growth factor (FGF) signalling at the tip of the dorsal branches generates a ‘pulling’ force believed to promote cell elongation and cell intercalation, which account for the final branch extension. Here, we used a variety of experimental conditions to study the contribution of cell elongation and cell intercalation to morphogenesis and analysed their mutual requirements. We provide evidence that cell intercalation does not require cell elongation and vice versa. We also show that the two cell behaviours are controlled by independent but simultaneous mechanisms, and that cell elongation is sufficient to account for full extension of the dorsal branch, while cell intercalation has a specific role in setting the diameter of this structure. Thus, rather than viewing changes in cell shape and cell intercalation as just redundant events that add robustness to a given morphogenetic process, we find that they can also act by contributing to different features of tissue architecture.
An improved statistical approach for reconstructing past climates from biotic assemblages
Authors: Liu Mengmeng , Prentice Iain Colin , ter Braak Cajo J. F. , Harrison Sandy P.
Published: November 2020

Quantitative reconstructions of past climates are an important resource for evaluating how well climate models reproduce climate changes. One widely used statistical approach for making such reconstructions from fossil biotic assemblages is weighted averaging partial least-squares regression (WA-PLS). There is however a known tendency for WA-PLS to yield reconstructions compressed towards the centre of the climate range used for calibration, potentially biasing the reconstructed past climates. We present an improvement of WA-PLS by assuming that: (i) the theoretical abundance of each taxon is unimodal with respect to the climate variable considered; (ii) observed taxon abundances follow a multinomial distribution in which the total abundance of a sample is climatically uninformative; and (iii) the estimate of the climate value at a given site and time makes the observation most probable, i.e. it maximizes the log-likelihood function. This climate estimate is approximated by weighting taxon abundances in WA-PLS by the inverse square of their climate tolerances. We further improve the approach by considering the frequency ( 
fx
) of the climate variable in the training dataset. Tolerance-weighted WA-PLS with
fx
correction greatly reduces the compression bias, compared with WA-PLS, and improves model performance in reconstructions based on an extensive modern pollen dataset.
On relativistic gasdynamics: invariance under a class of reciprocal-type transformations and integrable Heisenberg spin connections
Authors: Rogers C. , Ruggeri T. , Schief W. K.
Published: November 2020

A classical system of conservation laws descriptive of relativistic gasdynamics is examined. In the two-dimensional stationary case, the system is shown to be invariant under a novel multi-parameter class of reciprocal transformations. The class of invariant transformations originally obtained by Bateman in non-relativistic gasdynamics in connection with lift and drag phenomena is retrieved as a reduction in the classical limit. In the general 3+1-dimensional case, it is demonstrated that Synge’s geometric characterization of the pressure being constant along streamlines encapsulates a three-dimensional extension of an integrable Heisenberg spin equation.
Racing against change: understanding dispersal and persistence to improve species' conservation prospects
Authors: Kerr Jeremy T.
Published: November 2020

Climate change is contributing to the widespread redistribution, and increasingly the loss, of species. Geographical range shifts among many species were detected rapidly after predictions of the potential importance of climate change were specified 35 years ago: species are shifting their ranges towards the poles and often to higher elevations in mountainous areas. Early tests of these predictions were largely qualitative, though extraordinarily rapid and broadly based, and statistical tests distinguishing between climate change and other global change drivers provided quantitative evidence that climate change had already begun to cause species’ geographical ranges to shift. I review two mechanisms enabling this process, namely development of approaches for accounting for dispersal that contributes to range expansion, and identification of factors that alter persistence and lead to range loss. Dispersal in the context of range expansion depends on an array of processes, like population growth rates in novel environments, rates of individual species movements to new locations, and how quickly areas of climatically tolerable habitat shift. These factors can be tied together in well-understood mathematical frameworks or modelled statistically, leading to better prediction of extinction risk as climate changes. Yet, species' increasing exposures to novel climate conditions can exceed their tolerances and raise the likelihood of local extinction and consequent range losses. Such losses are the consequence of processes acting on individuals, driven by factors, such as the growing frequency and severity of extreme weather, that contribute local extinction risks for populations and species. Many mechanisms can govern how species respond to climate change, and rapid progress in global change research creates many opportunities to inform policy and improve conservation outcomes in the early stages of the sixth mass extinction.