bluuebunny/crossref_metadata_2025 huggingface dataset:
A245 IGG4- RELATED DISEASE AS A RARE CAUSE OF GASTRIC OUTLET OBSTRUCTION: A CASE REPORT AND LITERATURE REVIEW
Authors: Almudaires A , Alzahrani M , Chen L , Qumosani K
Published: March 2021

Background

IgG4- related disease (IgG4-RD) is a newly recognized systemic fibroinflammatory condition that can affect a wide range of organs, including the pancreas, biliary system, retroperitoneum, lymph nodes and salivary glands. However, gastrointestinal luminal involvement is very rare, and the presentation with isolated gastrointestinal obstruction is extremely unusual.

Aims

We present a case of IgG4-RD presenting with gastric outlet obstruction secondary to severe duodenal stricture.

Methods

A 59-year-old female presented with 6 months history of abdominal pain, postprandial nausea and vomiting associated with significant weight loss. CT showed circumferential wall thickening of the 2ndand 3rd parts of the duodenum with gastroscopy showing severe ulcerated duodenal stricture that could not be passed through. Biopsies from the ulcerated area did not reveal a specific etiology, but malignancy could not be excluded, and the decision was made to pursue surgical management with Whipple’s procedure.

Surgical pathology revealed IgG4 related disease in the form of an ulcerated gastric mass invading the duodenum and the pancreas with normal serum IgG4 level. Postoperatively, the patient developed anastomotic leak that was managed conservatively with antibiotics and drainage resulting in significant improvement in her symptoms. MRCP did not show any pancreatic or biliary abnormalities.

Results

A few weeks later, she represented with abdominal pain as well as nausea and vomiting. CT scan revealed severe inflammatory changes at the anastomosis site with mucosal thickening concerning for persistent leak. However, as she was optimally treated before, it was concluded that these changes are likely related to recurrent IgG4-RD. To induce remission, prednisone was started with remarkable improvement in her symptoms within two weeks, and complete resolution of the previous inflammatory changes around the anastomosis on repeat imaging. Subsequently, she was started on mycophenolate mofetil (MMF) with a slow prednisone taper.

Conclusions

IgG4-RD involving the gastrointestinal tract is rare with rare cases reported in the literature presenting in variable ways. Our case demonstrates the possibility of IgG4-RD presenting as gastric outlet obstruction; IgG4-RD should be considered in the differential diagnosis of unexplained duodenal stricture or gastric outlet obstruction. IgG4-RD usually responds to steroids but long-term response rates to steroid-sparing agents, especially in the subset of patients with luminal IgG4-RD, remains to be seen.

Funding Agencies

None
Long-term variability of root production in bioenergy crops from ingrowth core measurements
Authors: Lei Cheyenne , Abraha Michael , Chen Jiquan , Su Yahn-Jauh
Published: March 2021

Aims

Long-term determination of root biomass production upon land-use conversion to biofuel crops is rare. To assess land-use legacy influences on belowground biomass accumulation, we converted 22-year-old Conservation Reserve Program (CRP) grasslands and 50+-year-old agricultural (AGR) lands to corn (C), switchgrass (Sw) and restored prairie (Pr) biofuel crops. We maintained one CRP grassland as a reference (Ref). We hypothesized that land-use history and crop type have significant effects on root density, with perennial crops on CRP grasslands having a higher root biomass productivity, while corn grown on former agricultural lands produce the lowest root biomass.

Methods

The ingrowth core method was used to determine in situ ingrowth root biomass, alongside measurements of aboveground net primary productivity (ANPP). Ancillary measurements, including air temperature, growing season length and precipitation were used to examine their influences on root biomass production.

Important Findings

Root biomass productivity was the highest in unconverted CRP grassland (1716 g m−2 yr−1) and lowest in corn fields (526 g m−2 yr−1). All perennial sites converted from CRP and AGR lands had lower root biomass and ANPP in the first year of planting but peaked in 2011 for switchgrass and a year later for restored prairies. Ecosystem stability was higher in restored prairies (AGR-Pr: 4.3 ± 0.11; CRP-Pr: 4.1 ± 0.10), with all monocultures exhibiting a lower stability. Root biomass production was positively related to ANPP (R2 = 0.40). Overall, attention should be given to root biomass accumulation in large-scale biofuel production as it is a major source of carbon sequestration.
A forward internal calculus for model generation inS4
Authors: Fiorentini Camillo , Ferrari Mauro
Published: March 2021

We propose an internal calculus to check the satisfiability of a set of formulas in ${\boldsymbol {S4}}$. Our calculus directly supports model extraction and is designed so to implement a forward proof-search strategy that can be understood as a top-down construction of a model. We prove that the extracted models have minimal height.
Labelled cyclic proofs for separation logic
Authors: Galmiche Didier , Méry Daniel
Published: March 2021

Separation logic (SL) is a logical formalism for reasoning about programs that use pointers to mutate data structures. It is successful for program verification as an assertion language to state properties about memory heaps using Hoare triples. Most of the proof systems and verification tools for ${\textrm{SL}}$ focus on the decidable but rather restricted symbolic heaps fragment. Moreover, recent proof systems that go beyond symbolic heaps are purely syntactic or labelled systems dedicated to some fragments of ${\textrm{SL}}$ and they mainly allow either the full set of connectives, or the definition of arbitrary inductive predicates, but not both. In this work, we present a labelled proof system, called ${\textrm{G}_{\textrm{SL}}}$, that allows both the definition of cyclic proofs with arbitrary inductive predicates and the full set of SL connectives. We prove its soundness and show that we can derive in ${\textrm{G}_{\textrm{SL}}}$ the built-in rules for data structures of another non-cyclic labelled proof system and also that ${\textrm{G}_{\textrm{SL}}}$ is strictly more powerful than that system.
Myocardial Bridging, the Hidden Risk Factor for Ischemia
Authors: Happach Vincenzo C , Delk Gerald T , Ganti Latha
Published: March 2021

Myocardial bridging is an uncommon cause of a quite common emergency department complaint for chest pain and is often associated with left ventricular hypertrophy. We present a case of an otherwise healthy middle-aged U.S. military service member who presented with acute coronary syndrome which was ultimately determined to be the result of myocardial bridging.
Variability of newly identified B-type stars observed by Kepler
Authors: Szewczuk Wojciech , Walczak Przemysław , Daszyńska-Daszkiewicz Jadwiga
Published: March 2021

Recent re-determination of stellar atmospheric parameters for a sample of stars observed during the Kepler mission allowed to enlarge the number of Kepler B-type stars. We present the detailed frequency analysis for all these objects. All stars exhibit pulsational variability with maximum amplitudes at frequencies corresponding to high-order g modes. Peaks that could be identified with low-order p/g modes are also extracted for a few stars. We identified some patters in the oscillation spectra that can be associated with the period spacings that can results from the asymptotic nature of the detected pulsational modes. We also tentatively confront the observed oscillation characteristics with predictions from linear non-adiabatic computations of stellar pulsations. For high-order g modes the traditional approximation was employed to include the effects of rotation on the frequency values and mode instability.
ALMA–IRDC – II. First high-angular resolution measurements of the 14N/15N ratio in a large sample of infrared-dark cloud cores
Authors: Fontani F , Barnes A T , Caselli P , Henshaw J D , Cosentino G , Jiménez-Serra I , Tan J C , Pineda J E , Law C Y
Published: March 2021

The 14N/15N ratio in molecules exhibits a large variation in star-forming regions, especially when measured from N2H+ isotopologues. However, there are only a few studies performed at high-angular resolution. We present the first interferometric survey of the 14N/15N ratio in N2H+ obtained with Atacama Large Millimeter Array observations towards four infrared-dark clouds harbouring 3 mm continuum cores associated with different physical properties. We detect N15NH+ (1–0) in $\sim 20\!-\!40{{\ \rm per\ cent}}$ of the cores, depending on the host cloud. The 14N/15N values measured towards the millimetre continuum cores range from a minimum of ∼80 up to a maximum of ∼400. The spread of values is narrower than that found in any previous single-dish survey of high-mass star-forming regions and than that obtained using the total power data only. This suggests that the 14N/15N ratio is on average higher in the diffuse gaseous envelope of the cores and stresses the need for high-angular resolution maps to measure correctly the 14N/15N ratio in dense cores embedded in IRDCs. The average 14N/15N ratio of ∼210 is also lower than the interstellar value at the Galactocentric distance of the clouds (∼300–330), although the sensitivity of our observations does not allow us to unveil 14N/15N ratios higher than ∼400. No clear trend is found between the 14N/15N ratio and the core physical properties. We find only a tentative positive trend between 14N/15N and H2 column density. However, firmer conclusions can be drawn only with higher sensitivity measurements.
Mitigating contamination in LSS surveys: a comparison of methods
Authors: Weaverdyck Noah , Huterer Dragan
Published: March 2021

Future large-scale structure surveys will measure the locations and shapes of billions of galaxies. The precision of such catalogues will require meticulous treatment of systematic contamination of the observed fields. We compare several existing methods for removing such systematics from galaxy clustering measurements. We show how all the methods, including the popular pseudo-Cℓ Mode Projection and Template Subtraction methods, can be interpreted under a common regression framework and use this to suggest improved estimators. We show how methods designed to mitigate systematics in the power spectrum can be used to produce clean maps, which are necessary for cosmological analyses beyond the power spectrum, and we extend current methods to treat the next-order multiplicative contamination in observed maps and power spectra, which reduced power spectrum errors from $\Delta \chi ^2_{\rm C_\ell }\simeq 10$ to ≃ 1 in simulated analyses. Two new mitigation methods are proposed, which incorporate desirable features of current state-of-the-art methods while being simpler to implement. Investigating the performance of all the methods on a common set of simulated measurements from Year 5 of the Dark Energy Survey, we test their robustness to various analysis cases. Our proposed methods produce improved maps and power spectra when compared to current methods, while requiring almost no user tuning. We end with recommendations for systematics mitigation in future surveys, and note that the methods presented are generally applicable beyond the galaxy distribution to any field with spatial systematics.
The PAU Survey: narrow-band photometric redshifts using Gaussian processes
Authors: Soo John Y H , Joachimi Benjamin , Eriksen Martin , Siudek Małgorzata , Alarcon Alex , Cabayol Laura , Carretero Jorge , Casas Ricard , Castander Francisco J , Fernández Enrique , García-Bellido Juan , Gaztanaga Enrique , Hildebrandt Hendrik , Hoekstra Henk , Miquel Ramon , Padilla Cristobal , Sánchez Eusebio , Serrano Santiago , Tallada-Crespí Pau
Published: March 2021

We study the performance of the hybrid template machine learning photometric redshift (photo-z) algorithm delight, which uses Gaussian processes, on a subset of the early data release of the Physics of the Accelerating Universe Survey (PAUS). We calibrate the fluxes of the 40 PAUS narrow bands with six broad-band fluxes (uBVriz) in the Cosmic Evolution Survey (COSMOS) field using three different methods, including a new method that utilizes the correlation between the apparent size and overall flux of the galaxy. We use a rich set of empirically derived galaxy spectral templates as guides to train the Gaussian process, and we show that our results are competitive with other standard photometric redshift algorithms. delight achieves a photo-z 68th percentile error of σ68 = 0.0081(1 + z) without any quality cut for galaxies with iauto < 22.5 as compared to 0.0089(1 + z) and 0.0202(1 + z) for the bpz and annz2 codes, respectively. delight is also shown to produce more accurate probability distribution functions for individual redshift estimates than bpz and annz2. Common photo-z outliers of delight and bcnz2 (previously applied to PAUS) are found to be primarily caused by outliers in the narrow-band fluxes, with a small number of cases potentially indicating spectroscopic redshift failures in the reference sample. In the process, we introduce performance metrics derived from the results of bcnz2 and delight, allowing us to achieve a photo-z quality of σ68 < 0.0035(1 + z) at a magnitude of iauto < 22.5 while keeping 50 per cent objects of the galaxy sample.
Impact of rotation on the evolution of convective vortices in collapsing stars
Authors: Abdikamalov E , Foglizzo T , Mukazhanov O
Published: March 2021

We study the impact of rotation on the hydrodynamic evolution of convective vortices during stellar collapse. Using linear hydrodynamics equations, we study the evolution of the vortices from their initial radii in convective shells down to smaller radii where they are expected to encounter the supernova shock. We find that the evolution of vortices is mainly governed by two effects: the acceleration of infall and the accompanying speed up of rotation. The former effect leads to the radial stretching of vortices, which limits the vortex velocities. The latter effect leads to the angular deformation of vortices in the direction of rotation, amplifying their non-radial velocity. We show that the radial velocities of the vortices are not significantly affected by rotation. We study acoustic wave emission and find that it is not sensitive to rotation. Finally, we analyse the impact of the corotation point and find that it has a small impact on the overall acoustic wave emission.
Interrogating accessibility of telomeric sequences with FRET-PAINT: evidence for length-dependent telomere compaction
Authors: Mustafa Golam , Shiekh Sajad , GC Keshav , Abeysirigunawardena Sanjaya , Balci Hamza
Published: March 2021

Single-stranded telomeric overhangs are ∼200 nucleotides long and can form tandem G-quadruplex (GQ) structures, which reduce their accessibility to nucleases and proteins that activate DNA damage response. Whether these tandem GQs further stack to form compact superstructures, which may provide better protection for longer telomeres, is not known. We report single-molecule measurements where the accessibility of 24–144 nucleotide long human telomeric DNA molecules is interrogated by a short PNA molecule that is complementary to a single GGGTTA repeat, as implemented in the FRET-PAINT method. Binding of the PNA strand to available GGGTTA sequences results in discrete FRET bursts which were analyzed in terms of their dwell times, binding frequencies, and topographic distributions. The binding frequencies were greater for binding to intermediate regions of telomeric DNA compared to 3′- or 5′-ends, suggesting these regions are more accessible. Significantly, the binding frequency per telomeric repeat monotonically decreased with increasing telomere length. These results are consistent with telomeres forming more compact structures at longer lengths, reducing accessibility of these critical genomic sites.
The interdependence imperative: business strategy, complementarities, and economic policy
Authors: Yang Mu-Jeung
Published: March 2021

An enduring idea in economics and management sciences is that successful business strategies exploit complementarities across management practices within a firm. From this complementarity perspective, the success of business strategy requires utilizing a variety of interdependencies across management practices. Navigating large arrays of possible interdependencies implies that strategic decision-making is often conducted under high complexity and uncertainty. This paper provides an introduction to the conceptual foundations of complementarities in business strategy, and its implications for strategic decision-making and managerial learning. Against this backdrop, I outline issues of measurement and data collection for strategy practices, drawing on recent measurement efforts by academic researchers as well as national statistical agencies. The last part of the paper discusses how increased large-scale data collection on firm activity complementarities and strategy practices can inform a variety of policy areas, such as antitrust policy and merger review, industrial and innovation policy, tax policy, and public–private partnerships.
Active prey selection in developing larvae of Atlantic bluefin tuna (Thunnus thynnus) in spawning grounds of the Gulf of Mexico
Authors: Shiroza Akihiro , Malca Estrella , Lamkin John T , Gerard Trika , Landry Michael R , Stukel Michael R , Laiz-Carrión Raúl , Swalethorp Rasmus
Published: March 2021

Bluefin tuna spawn in restricted areas of subtropical oligotrophic seas. Here, we investigate the zooplankton prey and feeding selectivity of early larval stages of Atlantic bluefin tuna (ABT, Thunnus thynnus) in larval rearing habitat of the Gulf of Mexico. Larvae and zooplankton were collected during two multi-day Lagrangian experiments during peak spawning in May 2017 and 2018. Larvae were categorized by flexion stage and standard length. We identified, enumerated and sized zooplankton from larval gut contents and in the ambient community. Ciliates were quantitatively important (up to 9%) in carbon-based diets of early larvae. As larvae grew, diet composition and prey selection shifted from small copepod nauplii and calanoid copepodites to larger podonid cladocerans, which accounted for up to 70% of ingested carbon. Even when cladoceran abundances were <0.2 m−3, they comprised 23% of postflexion stage diet. Feeding behaviors of larvae at different development stages were more specialized, and prey selection narrowed to appendicularians and primarily cladocerans when these taxa were more abundant. Our findings suggest that ABT larvae have the capacity to switch from passive selection, regulated by physical factors, to active selection of presumably energetically optimal prey.
Daily temperature cycles promote alternative splicing of RNAs encoding SR45a, a splicing regulator in maize
Authors: Li Zhaoxia , Tang Jie , Bassham Diane C , Howell Stephen H.
Published: March 2021

Elevated temperatures enhance alternative RNA splicing in maize (Zea mays) with the potential to expand the repertoire of plant responses to heat stress. Alternative RNA splicing generates multiple RNA isoforms for many maize genes, and here we observed changes in the pattern of RNA isoforms with temperature changes. Increases in maximum daily temperature elevated the frequency of the major modes of alternative splices (AS), in particular retained introns and skipped exons. The genes most frequently targeted by increased AS with temperature encode factors involved in RNA processing and plant development. Genes encoding regulators of alternative RNA splicing were themselves among the principal AS targets in maize. Under controlled environmental conditions, daily changes in temperature comparable to field conditions altered the abundance of different RNA isoforms, including the RNAs encoding the splicing regulator SR45a, a member of the SR45 gene family. We established an “in protoplast” RNA splicing assay to show that during the afternoon on simulated hot summer days, SR45a RNA isoforms were produced with the potential to encode proteins efficient in splicing model substrates. With the RNA splicing assay, we also defined the exonic splicing enhancers that the splicing-efficient SR45a forms utilize to aid in the splicing of model substrates. Hence, with rising temperatures on hot summer days, SR45a RNA isoforms in maize are produced with the capability to encode proteins with greater RNA splicing potential.
Simplified Universal Grading of Lumbar Spine MRI Degenerative Findings: Inter-Reader Agreement of Non-Radiologist Spine Experts
Authors: Miskin Nityanand , Isaac Zacharia , Lu Yi , Makhni Melvin C , Sarno Danielle L , Smith Timothy R , Zampini Jay M , Mandell Jacob C
Published: March 2021

Objective

1) To describe a simplified multidisciplinary grading system for the most clinically relevant lumbar spine degenerative changes. 2) To measure the inter-reader variability among non-radiologist spine experts in their use of the classification system for interpretation of a consecutive series of lumbar spine magnetic resonance imaging (MRI) examinations.

Methods

ATS multidisciplinary and collaborative standardized grading of spinal stenosis, foraminal stenosis, lateral recess stenosis, and facet arthropathy was developed. Our institution’s picture archiving and communication system was searched for 50 consecutive patients who underwent non-contrast MRI of the lumbar spine for chronic back pain, radiculopathy, or symptoms of spinal stenosis. Three fellowship-trained spine subspecialists from neurosurgery, orthopedic surgery, and physiatry interpreted the 50 exams using the classification at the L4–L5 and L5–S1 levels. Inter-reader agreement was assessed with Cohen’s kappa coefficient.

Results

For spinal stenosis, the readers demonstrated substantial agreement (κ = 0.702). For foraminal stenosis and facet arthropathy, the three readers demonstrated moderate agreement (κ = 0.544, and 0.557, respectively). For lateral recess stenosis, there was fair agreement (κ = 0.323).

Conclusions

A simplified universal grading system of lumbar spine MRI degenerative findings is newly described. Use of this multidisciplinary grading system in the assessment of clinically relevant degenerative changes revealed moderate to substantial agreement among non-radiologist spine physicians. This standardized grading system could serve as a foundation for interdisciplinary communication.
Effects of Abdominal Binders on Postoperative Pain and Functional Recovery: A Systematic Review and Meta-Analysis
Authors: Sun Xin , Wei Qingchuan , Fu Chenying , Zhang Qing , Liang Zejun , Peng Lihong , Chen Li , He Chengqi , Wei Quan
Published: March 2021

Objective

This study aimed to assess the effectiveness of abdominal binders (ABs) on postoperative pain and functional recovery in patients receiving abdominal surgery.

Methods

The Pubmed, Embase, Cochrane Library, and PEDro databases were searched for clinical trials published up to November 30, 2019. Randomized controlled trials that compared the effects of wearing an AB to not wearing an AB in participants after abdominal surgery were included. The primary outcomes were pain, pulmonary function, and physical function, as assessed by the visual analog scale score, a spirometry device, and the 6-minute walk test, respectively. The registration number of this review in PROSPERO is CRD42020165303.

Results

Fourteen trials involving 1,317 participants were included. Pooled estimates for the visual analog scale score and the 6-minute walk test showed significant differences between the AB group and the control group, especially on the fourth day following surgery (mean difference [MD] = -2.82, 95% confidence interval [CI] = -3.41 to -2.22; P < 0.00001; MD = 50.97 meters, 95% CI = 39.99–61.95 m; P < 0.00001). However, no significant differences were found in pulmonary function (forced vital capacity [FVC]: MD = 0.01, 95% CI = -0.29 to -0.32; P = 0.94; forced expiratory volume during the first second [FEV1]: MD = -0.05, 95% CI = -0.24 to 0.14; P = 0.63; FEV1/FVC: MD = 3.14, 95% CI = -2.78 to 9.06; P = 0.30).

Conclusion

ABs probably improve postoperative pain and physical function, especially on the fourth day or more following abdominal surgery, but they have no effects on pulmonary function.
Adapting a Traumatic Brain Injury Goals-of-Care Decision Aid for Critically Ill Patients to Intracerebral Hemorrhage and Hemispheric Acute Ischemic Stroke
Authors: Goostrey Kelsey J. , Lee Christopher , Jones Kelsey , Quinn Thomas , Moskowitz Jesse , Pach Jolanta J. , Knies Andrea K. , Shutter Lori , Goldberg Robert , Mazor Kathleen M. , Hwang David Y. , Muehlschlegel Susanne
Published: March 2021

Objectives:

Families in the neurologic ICU urgently request goals-of-care decision support and shared decision-making tools. We recently developed a goals-of-care decision aid for surrogates of critically ill traumatic brain injury patients using a systematic development process adherent to the International Patient Decision Aid Standards. To widen its applicability, we adapted this decision aid to critically ill patients with intracerebral hemorrhage and large hemispheric acute ischemic stroke.

Design:

Prospective observational study.

Setting:

Two academic neurologic ICUs.

Subjects:

Twenty family members of patients in the neurologic ICU were recruited from July 2018 to October 2018.

Interventions:

None.

Measurements and Main Results:

We reviewed the existing critically ill traumatic brain injury patients decision aid for content and changed: 1) the essential background information, 2) disease-specific terminology to “hemorrhagic stroke” and “ischemic stroke”, and 3) disease-specific prognosis tailored to individual patients. We conducted acceptability and usability testing using validated scales. All three decision aids contain information from validated, disease-specific outcome prediction models, as recommended by international decision aid standards, including careful emphasis on their uncertainty. We replaced the individualizable icon arrays graphically depicting probabilities of a traumatic brain injury patient’s prognosis with icon arrays visualizing intracerebral hemorrhage and hemispheric acute ischemic stroke prognostic probabilities using high-quality disease-specific data. We selected the Intracerebral Hemorrhage Score with validated 12-month outcomes, and for hemispheric acute ischemic stroke, the 12-month outcomes from landmark hemicraniectomy trials. Twenty family members participated in acceptability and usability testing (n = 11 for the intracerebral hemorrhage decision aid; n = 9 for the acute ischemic stroke decision aid). Median usage time was 22 minutes (interquartile range, 16–26 min). Usability was excellent (median System Usability Scale = 84/100 [interquartile range, 61–93; with > 68 indicating good usability]); 89% of participants graded the decision aid content as good or excellent, and greater than or equal to 90% rated it favorably for information amount, balance, and comprehensibility.

Conclusions:

We successfully adapted goals-of-care decision aids for use in surrogates of critically ill patients with intracerebral hemorrhage and hemispheric acute ischemic stroke and found excellent usability and acceptability. A feasibility trial using these decision aids is currently ongoing to further validate their acceptability and test their feasibility for use in busy neurologic ICUs.
Physiologic Improvement in Respiratory Acidosis Using Extracorporeal Co 2 Removal With Hemolung Respiratory Assist System in the Management of Severe Respiratory Failure From Coronavirus Disease 2019
Authors: Akkanti Bindu , Jagpal Sugeet , Darwish Ribal , Saavedra Romero Ramiro , Scott L. Keith , Dinh Kha , Hussain Sabiha , Radbel Jared , Saad Mohamed A. , Enfield Kyle B. , Conrad Steven A.
Published: March 2021

Objectives:

About 15% of hospitalized coronavirus disease 2019 patients require ICU admission, and most (80%) of these require invasive mechanical ventilation. Lung-protective ventilation in coronavirus disease 2019 acute respiratory failure may result in severe respiratory acidosis without significant hypoxemia. Low-flow extracorporeal Co
2 removal can facilitate lung-protective ventilation and avoid the adverse effects of severe respiratory acidosis. The objective was to evaluate the efficacy of extracorporeal Co
2 removal using the Hemolung Respiratory Assist System in correcting severe respiratory acidosis in mechanically ventilated coronavirus disease 2019 patients with severe acute respiratory failure.

Design:

Retrospective cohort analysis of patients with coronavirus disease 2019 mechanically ventilated with severe hypercapnia and respiratory acidosis and treated with low-flow extracorporeal Co
2 removal.

Setting:

Eight tertiary ICUs in the United States.

Patients:

Adult patients supported with the Hemolung Respiratory Assist System from March 1, to September 30, 2020.

Interventions:

Extracorporeal Co
2 removal with Hemolung Respiratory Assist System under a Food and Drug Administration emergency use authorization for coronavirus disease 2019.

Measurements and Main Results:

The primary outcome was improvement in pH and Paco
2 from baseline. Secondary outcomes included survival to decannulation, mortality, time on ventilator, and adverse events. Thirty-one patients were treated with Hemolung Respiratory Assist System with significant improvement in pH and Pco
2 in this cohort. Two patients experienced complications that prevented treatment. Of the 29 treated patients, 58% survived to 48 hours post treatment and 38% to hospital discharge. No difference in age or comorbidities were noted between survivors and nonsurvivors. There was significant improvement in pH (7.24 ± 0.12 to 7.35 ± 0.07; p < 0.0001) and Paco
2 (79 ± 23 to 58 ± 14; p < 0.0001) from baseline to 24 hours.

Conclusions:

In this retrospective case series of 29 patients, we have demonstrated efficacy of extracorporeal Co
2 removal using the Hemolung Respiratory Assist System to improve respiratory acidosis in patients with severe hypercapnic respiratory failure due to coronavirus disease 2019.
Conditional prediction of consecutive tumor evolution using cancer progression models: What genotype comes next?
Authors: Diaz-Colunga Juan , Diaz-Uriarte Ramon
Published: March 2021

Accurate prediction of tumor progression is key for adaptive therapy and precision medicine. Cancer progression models (CPMs) can be used to infer dependencies in mutation accumulation from cross-sectional data and provide predictions of tumor progression paths. However, their performance when predicting complete evolutionary trajectories is limited by violations of assumptions and the size of available data sets. Instead of predicting full tumor progression paths, here we focus on short-term predictions, more relevant for diagnostic and therapeutic purposes. We examine whether five distinct CPMs can be used to answer the question “Given that a genotype with n mutations has been observed, what genotype with n + 1 mutations is next in the path of tumor progression?” or, shortly, “What genotype comes next?”. Using simulated data we find that under specific combinations of genotype and fitness landscape characteristics CPMs can provide predictions of short-term evolution that closely match the true probabilities, and that some genotype characteristics can be much more relevant than global features. Application of these methods to 25 cancer data sets shows that their use is hampered by a lack of information needed to make principled decisions about method choice. Fruitful use of these methods for short-term predictions requires adapting method’s use to local genotype characteristics and obtaining reliable indicators of performance; it will also be necessary to clarify the interpretation of the method’s results when key assumptions do not hold.
Modified Oxacillin Resistant Staphylococcus aureus detected in neonatal intensive care patients
Authors: Gitman Melissa R. , Alburquerque Bremy , van de Guchte Adriana , Sullivan Mitchell J. , Obla Ajay , Polanco Jose , Chung Marilyn , Oussenko Irina , Smith Melissa L. , Samaroo Flora , Barackman Debbie , Altman Deena R. , Sordillo Emilia Mia , van Bakel Harm
Published: March 2021

Active surveillance in our neonatal intensive care unit identified Staphylococcus aureus cultures from two infants with heterogeneity in methicillin resistance between isolated subclones lacking mecA and mecC. Whole-genome analysis of 4 modified (MODSA) and 4 methicillin-susceptible (MSSA) subclones for each culture identified either truncating mutations in the cyclic diadenosine monophosphate phosphodiesterase enzyme (GdpP), or a nonsynonymous substitution in penicillin binding protein 2 (PBP2). These cases highlight the difficulty in identifying non-mecA/non-mecC-mediated methicillin-resistance in clinical laboratories.
Quantification of the spread of SARS-CoV-2 variant B.1.1.7 in Switzerland
Authors: Chen Chaoran , Nadeau Sarah , Topolsky Ivan , Manceau Marc , Huisman Jana S. , Jablonski Kim Philipp , Fuhrmann Lara , Dreifuss David , Jahn Katharina , Beckmann Christiane , Redondo Maurice , Noppen Christoph , Risch Lorenz , Risch Martin , Wohlwend Nadia , Kas Sinem , Bodmer Thomas , Roloff Tim , Stange Madlen , Egli Adrian , Eckerle Isabella , Kaiser Laurent , Denes Rebecca , Feldkamp Mirjam , Nissen Ina , Santacroce Natascha , Burcklen Elodie , Aquino Catharine , de Gouvea Andreia Cabral , Moccia Maria Domenica , Grüter Simon , Sykes Timothy , Opitz Lennart , White Griffin , Neff Laura , Popovic Doris , Patrignani Andrea , Tracy Jay , Schlapbach Ralph , Dermitzakis Emmanouil T. , Harshman Keith , Xenarios Ioannis , Pegeot Henri , Cerutti Lorenzo , Penet Deborah , Blin Anthony , Elies Melyssa , Althaus Christian L. , Beisel Christian , Beerenwinkel Niko , Ackermann Martin , Stadler Tanja
Published: March 2021

Background

In December 2020, the United Kingdom (UK) reported a SARS-CoV-2 Variant of Concern (VoC) which is now named B.1.1.7. Based on initial data from the UK and later data from other countries, this variant was estimated to have a transmission fitness advantage of around 40-80% [1, 2, 3].

Aim

This study aims to estimate the transmission fitness advantage and the effective reproductive number of B.1.1.7 through time based on data from Switzerland.

Methods

We generated whole genome sequences from 11.8% of all confirmed SARS-CoV-2 cases in Switzerland between 14 December 2020 and 11 March 2021. Based on these data, we determine the daily frequency of the B.1.1.7 variant and quantify the variant’s transmission fitness advantage on a national and a regional scale.

Results

We estimate B.1.1.7 had a transmission fitness advantage of 43-52% compared to the other variants circulating in Switzerland during the study period. Further, we estimate B.1.1.7 had a reproductive number above 1 from 01 January 2021 until the end of the study period, compared to below 1 for the other variants. Specifically, we estimate the reproductive number for B.1.1.7 was 1.24 [1.07-1.41] from 01 January until 17 January 2021 and 1.18 [1.06-1.30] from 18 January until 01 March 2021 based on the whole genome sequencing data. From 10 March to 16 March 2021, once B.1.1.7 was dominant, we estimate the reproductive number was 1.14 [1.00-1.26] based on all confirmed cases. For reference, Switzerland applied more non-pharmaceutical interventions to combat SARS-CoV-2 on 18 January 2021 and lifted some measures again on 01 March 2021.

Conclusion

The observed increase in B.1.1.7 frequency in Switzerland during the study period is as expected based on observations in the UK. In absolute numbers, B.1.1.7 increased exponentially with an estimated doubling time of around 2-3.5 weeks. To monitor the ongoing spread of B.1.1.7, our plots are available online.
COVID-19 risk score as a public health tool to guide targeted testing: A demonstration study in Qatar
Authors: Abu-Raddad Laith J. , Dargham Soha , Chemaitelly Hiam , Coyle Peter , Al Kanaani Zaina , Al Kuwari Einas , Butt Adeel A. , Jeremijenko Andrew , Kaleeckal Anvar Hassan , Latif Ali Nizar , Shaik Riyazuddin Mohammad , Rahim Hanan F. Abdul , Nasrallah Gheyath K. , Yassine Hadi M. , Al Kuwari Mohamed G. , Al Romaihi Hamad Eid , Al-Thani Mohamed H. , Al Khal Abdullatif , Bertollini Roberto
Published: March 2021

Background

The objective of this study was to develop a Coronavirus Disease 2019 (COVID-19) risk score to guide targeted RT-PCR testing in Qatar.

Methods

The Qatar national COVID-19 testing database was analyzed. This database includes a total of 2,688,232 RT-PCR tests conducted between February 5, 2020-January 27, 2021. Logistic regression analyses were implemented to identify predictors of infection and to derive the COVID-19 risk score, as a tool to identify those at highest risk of having the infection. Score cut-off was determined using the receiving operating characteristic (ROC) curve based on maximum sum of sensitivity and specificity. The score’s performance diagnostics were assessed.

Results

Logistic regression analysis identified age, sex, and nationality as significant predictors of infection and were included in the risk score. The score’s scoring points were lower for females compared to males and higher for specific nationalities. The ROC curve was generated and the area under the curve was estimated at 0.63 (95% CI: 0.63-0.63). The score had a sensitivity of 59.4% (95% CI: 59.1%-59.7%), specificity of 61.1% (95% CI: 61.1%-61.2%), a positive predictive value of 10.9% (95% CI: 10.8%-10.9%), and a negative predictive value of 94.9% (94.9%-95.0%). The risk score derived early in the epidemic, based on data until only April 21, 2020, had a performance comparable to that of a score based on a year-long testing.

Conclusions

The concept and utility of a COVID-19 risk score were demonstrated in Qatar. Such a public health tool, based on a set of non-invasive and easily captured variables can have considerable utility in optimizing testing and suppressing infection transmission, while maximizing efficiency and use of available resources.
Nurturing diversity and inclusion in AI in Biomedicine through a virtual summer program for high school students
Authors: Oskotsky Tomiko , Bajaj Ruchika , Burchard Jillian , Cavazos Taylor , Chen Ina , Connell Will , Eaneff Stephanie , Grant Tianna , Kanungo Ishan , Lindquist Karla , Myers-Turnbull Douglas , Naing Zun Zar Chi , Tang Alice , Vora Bianca , Wang Jon , Karim Isha , Swadling Claire , Yang Janice ,   AI4ALL Student Cohort 2020, Sirota Marina
Published: March 2021

Artificial Intelligence (AI) has the power to improve our lives through a wide variety of applications, many of which fall into the healthcare space; however, a lack of diversity is contributing to flawed systems that perpetuate gender and racial biases, and limit how broadly AI can help people. The UCSF AI4ALL program was established in 2019 to address this issue by promoting diversity and inclusion in AI. The program targets high school students from underrepresented backgrounds in AI and gives them a chance to learn about AI with a focus on biomedicine. In 2020, the UCSF AI4ALL three-week program was held entirely online due to the COVID-19 pandemic. Thus students participated virtually to gain experience with AI, interact with diverse role models in AI, and learn about advancing health through AI. Specifically, they attended lectures in coding and AI, received an in-depth research experience through hands-on projects exploring COVID-19, and engaged in mentoring and personal development sessions with faculty, researchers, industry professionals, and undergraduate and graduate students, many of whom were women and from underrepresented racial and ethnic backgrounds. At the conclusion of the program, the students presented the results of their research projects at our final symposium. Comparison of pre- and post-program survey responses from students demonstrated that after the program, significantly more students were familiar with how to work with data and to evaluate and apply machine learning algorithms. There was also a nominally significant increase in the students’ knowing people in AI from historically underrepresented groups, feeling confident in discussing AI, and being aware of careers in AI. We found that we were able to engage young students in AI via our online training program and nurture greater inclusion in AI.
Transmission, infectivity, and antibody neutralization of an emerging SARS-CoV-2 variant in California carrying a L452R spike protein mutation
Authors: Deng Xianding , Garcia-Knight Miguel A , Khalid Mir M. , Servellita Venice , Wang Candace , Morris Mary Kate , Sotomayor-González Alicia , Glasner Dustin R , Reyes Kevin R , Gliwa Amelia S. , Reddy Nikitha P. , Sanchez San Martin Claudia , Federman Scot , Cheng Jing , Balcerek Joanna , Taylor Jordan , Streithorst Jessica A , Miller Steve , Kumar G. Renuka , Sreekumar Bharath , Chen Pei-Yi , Schulze-Gahmen Ursula , Taha Taha Y. , Hayashi Jennifer , Simoneau Camille R. , McMahon Sarah , Lidsky Peter V. , Xiao Yinghong , Hemarajata Peera , Green Nicole M. , Espinosa Alex , Kath Chantha , Haw Monica , Bell John , Hacker Jill K. , Hanson Carl , Wadford Debra A. , Anaya Carlos , Ferguson Donna , Lareau Liana F. , Frankino Phillip A. , Shivram Haridha , Wyman Stacia K. , Ott Melanie , Andino Raul , Chiu Charles Y.
Published: March 2021

We identified a novel SARS-CoV-2 variant by viral whole-genome sequencing of 2,172 nasal/nasopharyngeal swab samples from 44 counties in California. Named B.1.427/B.1.429 to denote its 2 lineages, the variant emerged around May 2020 and increased from 0% to >50% of sequenced cases from September 1, 2020 to January 29, 2021, exhibiting an 18.6-24% increase in transmissibility relative to wild-type circulating strains. The variant carries 3 mutations in the spike protein, including an L452R substitution. Our analyses revealed 2-fold increased B.1.427/B.1.429 viral shedding in vivo and increased L452R pseudovirus infection of cell cultures and lung organoids, albeit decreased relative to pseudoviruses carrying the N501Y mutation found in the B.1.1.7, B.1.351, and P.1 variants. Antibody neutralization assays showed 4.0 to 6.7-fold and 2.0-fold decreases in neutralizing titers from convalescent patients and vaccine recipients, respectively. The increased prevalence of a more transmissible variant in California associated with decreased antibody neutralization warrants further investigation.
COVID-19 vaccine distrust in Colombian university students: Frequency and associated variables
Authors: Campo-Arias Adalberto , Pedrozo-Pupo John Carlos
Published: March 2021

The study aimed to know the frequency and variables associated with COVID-19 vaccine distrust in students of a Colombian university. A cross-sectional study was carried out which participated emerging adult students of a Colombian university. A total of 1,136 students between 18 and 29 years (M= 22.0, SD = 3.0); most of them were female (66.0%), non-health students (82.8%), low-income (79.0%), and residents of urban areas (84.9%). It was frequent low institutional trust (74.8%), low cognitive, social capital (27.9%), low fear of COVID-19 (49.5%), low perceived stress related to COVID-19 (83.5%), and high COVID-19 vaccine distrust (78.9%). Non-health carrier (Adjusted OR = 3.63, 95%CI 2.58-5.10), rural residence (AOR = 1.85, 95%CI 1.13-3.04), low income (AOR = 1.84, 95%CI 1.31-2.57), and perceived stress related to COVID-19 (AOR = 1.74, 95%CI 1.20-2.54) were related to high COVID-19 vaccine distrust. In conclusion, COVID-19 vaccine distrust is high among emerging adult Colombian university students. The COVID-19 vaccine distrust is related to non-health science carriers, rural residents, low-income, and low-perceived stress related to COVID-19. The COVID-19 related health literacy should be improved in students of this university considering socio-cultural background.
Explainable AI for Retinal Prostheses: Predicting Electrode Deactivation from Routine Clinical Measures
Authors: Hu Zuying , Beyeler Michael
Published: March 2021

To provide appropriate levels of stimulation, retinal prostheses must be calibrated to an individual’s perceptual thresholds (‘system fitting’). Nonfunctional electrodes may then be deactivated to reduce power consumption and improve visual outcomes. However, thresholds vary drastically not just across electrodes but also over time, thus calling for a more flexible electrode deactivation strategy. Here we present an explainable artificial intelligence (XAI) model fit on a large longitudinal dataset that can 1) predict at which point in time the manufacturer chose to deactivate an electrode as a function of routine clinical measures (‘predictors’) and 2) reveal which of these predictors were most important. The model predicted electrode deactivation from clinical data with 60.8% accuracy. Performance increased to 75.3% with system fitting data, and to 84% when thresholds from follow-up examinations were available. The model further identified subject age and time since blindness onset as important predictors of electrode deactivation. An accurate XAI model of electrode deactivation that relies on routine clinical measures may benefit both the retinal implant and wider neuroprosthetics communities.
Heparin promotes fibrillation of most phenol soluble modulin peptides fromS. aureus: a possible strengthening of the bacterial biofilm
Authors: Najarzadeh Zahra , Zaman Masihuz , Serekaité Vita , Strømgaard Kristian , Andreasen Maria , Otzen Daniel E.
Published: March 2021

Phenol soluble modulins (PSMs) are virulence peptides secreted by differentStaphylococcus aureusstrains. In addition, PSMs are able to form amyloid fibrils which may strengthen the biofilm matrix. The highly sulfated glycosaminoglycan heparin promotesS.aureusinfection but the basis for this is unclear. We hypothesized that heparin promotes PSM fibrillation and in this way aids bacterial colonization. Here we address this hypothesis using a combination of different biophysical techniques along with peptide microarrays. We find that heparin accelerates fibrillation of all α-PSMs (except PSMα2) and δ-toxin, but inhibits β-PSMs’ fibrillation by blocking nucleation. Given thatS. aureussecretes higher levels of α-PSMs than β-PSMs peptidess, heparin is likely to overall promote fibrillation. Heparin binding is driven by multiple positively charged lysine residues in α-PSMs and δ-toxins, whose removal strongly reduces affinity. Binding of heparin does not alter the final fibril conformation. Rather, heparin provides a scaffold to catalyze or inhibit fibrillation. Our findings suggest that heparin may strengthen bacterial biofilm through increased PSM fibrillation.

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