bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous Quantitative Detection of IL-6 and PCT Using SERS magnetic immunoassay with sandwich structure
Authors: Wang Xiaomei , Ma Li , Hu Cunming , Liu Tingwei , Sun Shijiao , Liu Xinghui , Guan Ming
Published: March 2021

Sepsis is a systemic inflammatory response syndrome caused by infection. The mortality rate is as high as 30%−50%. Early diagnosis and treatment can significantly improve the mortality of patients with sepsis. Therefore, we have developed a SERS-based magnetic immunoassay method that uses the principle of sandwich method to quantitatively detect Interleukin 6 (IL-6) and Procalcitonin (PCT). In this article, two different Raman reporter molecules are embedded in the middle of the Au@Ag shell and coupled with the tracer antibody to form a SERS immunoprobe. Biotin was coupled with capture antibody to form a sandwich structure when participating in the immune response. Streptavidin and biotin systems have extremely high binding affinity. The sandwich structure is quickly captured by SA magnetic beads and then applied with a magnetic field to enrich the magnetic beads. Finally, simultaneous quantitative detection is achieved by the intensity of the two Raman reporter characteristic peaks on the solution magnetic beads. IL-6 and PCT showed a good relationship between 0−1000 pg ml−1 and 0−20 ng ml−1, respectively, and the limits of detection were 0.54 pg ml−1 and 0.042 ng ml−1, respectively. The recovery rate was between 89.8% and 104.2%, both intra-assay and inter-assay CV were ≤20%. No cross-reaction with C-reactive protein (100 μg ml−1), showing good specificity. This method provides a new technical reference for the clinical detection of sepsis biomarkers.
Statistical limitations in ion imaging
Authors: Collins-Fekete Charles-Antoine , Dikaios Nikolaos , Bär Esther , Evans Philip M
Published: March 2021

In this study, we investigated the capacity of various ion beams available for radiotherapy to produce high quality relative stopping power map acquired from energy-loss measurements. The image quality metrics chosen to compare the different ions were signal-to-noise ratio (SNR) as a function of dose and spatial resolution. Geant4 Monte Carlo simulations were performed for: hydrogen, helium, lithium, boron and carbon ion beams crossing a 20 cm diameter water phantom to determine SNR and spatial resolution. It has been found that protons possess a significantly larger SNR when compared with other ions at a fixed range (up to 36% higher than helium) due to the proton nuclear stability and low dose per primary. However, it also yields the lowest spatial resolution against all other ions, with a resolution lowered by a factor 4 compared to that of carbon imaging, for a beam with the same initial range. When comparing for a fixed spatial resolution of 10 lp cm−1, carbon ions produce the highest image quality metrics with proton ions producing the lowest. In conclusion, it has been found that no ion can maximize all image quality metrics simultaneously and that a choice must be made between spatial resolution, SNR, and dose.
Nonlocal generalized quantum measurements of bipartite spin products without maximal entanglement
Authors: Vidil P , Edamatsu K
Published: March 2021

Measuring a nonlocal observable on a space-like separated quantum system is a resource-hungry and experimentally challenging task. Several theoretical measurement schemes have already been proposed to increase its feasibility, using a shared maximally-entangled ancilla. We present a new approach to this problem, using the language of generalized quantum measurements, to show that it is actually possible to measure a nonlocal spin product observable without necessarily requiring a maximally-entangled ancilla. This approach opens the door to more economical arbitrary-strength nonlocal measurements, with applications ranging from nonlocal weak values to possible new tests of Bell inequalities. The relation between measurement strength and the amount of ancillary entanglement needed is made explicit, bringing a new perspective on the links that tie quantum nonlocality, entanglement and information transmission together.
Life Cycle Greenhouse Gas Emissions of Gastrointestinal Biopsies in a Surgical Pathology Laboratory
Authors: Gordon Ilyssa O , Sherman Jodi D , Leapman Michael , Overcash Michael , Thiel Cassandra L
Published: March 2021

Objectives

Given adverse health effects of climate change and contributions of the US health care sector to greenhouse gas (GHG) emissions, environmentally sustainable delivery of care is needed. We applied life cycle assessment to quantify GHGs associated with processing a gastrointestinal biopsy in order to identify emissions hotspots and guide mitigation strategies.

Methods

The biopsy process at a large academic pathology laboratory was grouped into steps. Each supply and reagent was catalogued and postuse treatment noted. Energy consumption was estimated for capital equipment. Two common scenarios were considered: 1 case with 1 specimen jar (scenario 1) and 1 case with 3 specimen jars (scenario 2).

Results

Scenario 1 generated 0.29 kg of carbon dioxide equivalents (kg CO2e), whereas scenario 2 resulted in 0.79 kg CO2e—equivalent to 0.7 and 2.0 miles driven, respectively. The largest proportion of GHGs (36%) in either scenario came from the tissue processor step. The second largest contributor (19%) was case accessioning, mostly attributable to production of single-use disposable jars.

Conclusions

Applied to more than 20 million biopsies performed in the US annually, emissions from biopsy processing is equivalent to yearly GHG emissions from 1,200 passenger cars. Mitigation strategies may include modification of surveillance guidelines to include the number of specimen jars.
Detecting m6A methylation regions from Methylated RNA Immunoprecipitation Sequencing
Authors: Guo Zhenxing , Shafik Andrew M , Jin Peng , Wu Zhijin , Wu Hao
Published: March 2021

Motivation

The post-transcriptional epigenetic modification on mRNA is an emerging field to study the gene regulatory mechanism and their association with diseases. Recently developed high-throughput sequencing technology named Methylated RNA Immunoprecipitation Sequencing (MeRIP-seq) enables one to profile mRNA epigenetic modification transcriptome wide. A few computational methods are available to identify transcriptome-wide mRNA modification, but they are either limited by over-simplified model ignoring the biological variance across replicates or suffer from low accuracy and efficiency.

Results

In this work, we develop a novel statistical method, based on an empirical Bayesian hierarchical model, to identify mRNA epigenetic modification regions from MeRIP-seq data. Our method accounts for various sources of variations in the data through rigorous modeling and applies shrinkage estimation by borrowing information from transcriptome-wide data to stabilize the parameter estimation. Simulation and real data analyses demonstrate that our method is more accurate, robust and efficient than the existing peak calling methods.

Availability and implementation

Our method TRES is implemented as an R package and is freely available on Github at https://github.com/ZhenxingGuo0015/TRES.

Supplementary information

Supplementary data are available at Bioinformatics online.
Segregation of functional networks is associated with cognitive resilience in Alzheimer’s disease
Authors: Ewers Michael , Luan Ying , Frontzkowski Lukas , Neitzel Julia , Rubinski Anna , Dichgans Martin , Hassenstab Jason , Gordon Brian A , Chhatwal Jasmeer P , Levin Johannes , Schofield Peter , Benzinger Tammie L S , Morris John C , Goate Alison , Karch Celeste M , Fagan Anne M , McDade Eric , Allegri Ricardo , Berman Sarah , Chui Helena , Cruchaga Carlos , Farlow Marty , Graff-Radford Neill , Jucker Mathias , Lee Jae-Hong , Martins Ralph N , Mori Hiroshi , Perrin Richard , Xiong Chengjie , Rossor Martin , Fox Nick C , O’Connor Antoinette , Salloway Stephen , Danek Adrian , Buerger Katharina , Bateman Randall J , Habeck Christian , Stern Yaakov , Franzmeier Nicolai ,   for the Alzheimer’s Disease Neuroimaging Initiative and the Dominantly Inherited Alzheimer Network
Published: March 2021

Cognitive resilience is an important modulating factor of cognitive decline in Alzheimer’s disease, but the functional brain mechanisms that support cognitive resilience remain elusive. Given previous findings in normal ageing, we tested the hypothesis that higher segregation of the brain’s connectome into distinct functional networks represents a functional mechanism underlying cognitive resilience in Alzheimer’s disease. Using resting-state functional MRI, we assessed both resting-state functional MRI global system segregation, i.e. the balance of between-network to within-network connectivity, and the alternate index of modularity Q as predictors of cognitive resilience. We performed all analyses in two independent samples for validation: (i) 108 individuals with autosomal dominantly inherited Alzheimer’s disease and 71 non-carrier controls; and (ii) 156 amyloid-PET-positive subjects across the spectrum of sporadic Alzheimer’s disease and 184 amyloid-negative controls. In the autosomal dominant Alzheimer’s disease sample, disease severity was assessed by estimated years from symptom onset. In the sporadic Alzheimer’s sample, disease stage was assessed by temporal lobe tau-PET (i.e. composite across Braak stage I and III regions). In both samples, we tested whether the effect of disease severity on cognition was attenuated at higher levels of functional network segregation. For autosomal dominant Alzheimer’s disease, we found higher functional MRI-assessed system segregation to be associated with an attenuated effect of estimated years from symptom onset on global cognition (P = 0.007). Similarly, for patients with sporadic Alzheimer’s disease, higher functional MRI-assessed system segregation was associated with less decrement in global cognition (P = 0.001) and episodic memory (P = 0.004) per unit increase of temporal lobe tau-PET. Confirmatory analyses using the alternate index of modularity Q revealed consistent results. In conclusion, higher segregation of functional connections into distinct large-scale networks supports cognitive resilience in Alzheimer’s disease.
EORTC/MSGERC Definitions of Invasive Fungal Diseases: Summary of Activities of the Intensive Care Unit Working Group
Authors: Bassetti Matteo , Azoulay Elie , Kullberg Bart-Jan , Ruhnke Markus , Shoham Shmuel , Vazquez Jose , Giacobbe Daniele Roberto , Calandra Thierry
Published: March 2021

The EORTC/MSGERC recently revised and updated the consensus definitions of invasive fungal disease (IFD). These definitions primarily focus on patients with cancer and stem cell or solid-organ transplant patients. They may therefore not be suitable for intensive care unit (ICU) patients. More in detail, while the definition of proven IFD applies to a broad range of hosts, the categories of probable and possible IFD were primarily designed for classical immunocompromised hosts and may therefore not be ideal for other populations. Moreover, the scope of the possible category of IFD has been diminished in the recently revised definitions for classically immunocompromised hosts. Diagnosis of IFD in the ICU presents many challenges, which are different for invasive candidiasis and for invasive aspergillosis. The aim of this article is to review progresses made in recent years and difficulties remaining in the development of definitions applicable in the ICU setting.
Engineering and Functional Evaluation of Neutralizing Antibody Fragments Against Congenital Toxoplasmosis
Authors: di Tommaso Anne , Juste Matthieu O , Lakhrif Zineb , Mévélec Marie-Noëlle , Borowczyk Coraline , Hammeni Pierre , Désoubeaux Guillaume , Van Langendonck Nathalie , Debierre-Grockiego Françoise , Aubrey Nicolas , Dimier-Poisson Isabelle
Published: March 2021

Maternal-fetal transmission of Toxoplasma gondii tachyzoites acquired during pregnancy has potentially dramatic consequences for the fetus. Current reference-standard treatments are not specific to the parasite and can induce severe side effects. In order to provide treatments with a higher specificity against toxoplasmosis, we developed antibody fragments—single-chain fragment variable (scFv) and scFv fused with mouse immunoglobulin G2a crystallizable fragment (scFv-Fc)—directed against the major surface protein SAG1. After validating their capacity to inhibit T. gondii proliferation in vitro, the antibody fragments’ biological activity was assessed in vivo using a congenital toxoplasmosis mouse model. Dams were treated by systemic administration of antibody fragments and with prevention of maternal-fetal transmission being used as the parameter of efficacy. We observed that both antibody fragments prevented T. gondii dissemination and protected neonates, with the scFv-Fc format having better efficacy. These data provide a proof of concept for the use of antibody fragments as effective and specific treatment against congenital toxoplasmosis and provide promising leads.
Stress intensity factors for cusp-type crack problem under mechanical and thermal loading
Authors: Chen F M , Chao C K , Chiu C C , Noda N A
Published: March 2021

The general solutions of the stress intensity factors (SIFs) for a cusp-type crack problem under remote uniform mechanical and thermal loads are presented in this work. According to the complex variable theory and the method of conformal mapping, a symmetric airfoil crack is mapped onto a unit circle, and both the temperature and stress potentials are used to solve the relevant boundary-value problems. By introducing the auxiliary function and applying the analytical continuation theorem, the SIFs at the cusp-type crack tip can be analytically determined. The obtained SIF results are dependent on the geometric configurations of the cusp-type crack components and the magnitudes of the mechanical and thermal loads. For some combinations of combined loads, the SIF is maximized, and the system has a high risk of damage.
Plant SWEETs: from sugar transport to plant–pathogen interaction and more unexpected physiological roles
Authors: Breia Richard , Conde Artur , Badim Hélder , Fortes Ana Margarida , Gerós Hernâni , Granell Antonio
Published: March 2021

Sugars Will Eventually be Exported Transporters (SWEETs) have important roles in numerous physiological mechanisms where sugar efflux is critical, including phloem loading, nectar secretion, seed nutrient filling, among other less expected functions. They mediate low affinity and high capacity transport, and in angiosperms this family is composed by 20 paralogs on average. As SWEETs facilitate the efflux of sugars, they are highly susceptible to hijacking by pathogens, making them central players in plant–pathogen interaction. For instance, several species from the Xanthomonas genus are able to upregulate the transcription of SWEET transporters in rice (Oryza sativa), upon the secretion of transcription-activator-like effectors. Other pathogens, such as Botrytis cinerea or Erysiphe necator, are also capable of increasing SWEET expression. However, the opposite behavior has been observed in some cases, as overexpression of the tonoplast AtSWEET2 during Pythium irregulare infection restricted sugar availability to the pathogen, rendering plants more resistant. Therefore, a clear-cut role for SWEET transporters during plant–pathogen interactions has so far been difficult to define, as the metabolic signatures and their regulatory nodes, which decide the susceptibility or resistance responses, remain poorly understood. This fuels the still ongoing scientific question: what roles can SWEETs play during plant–pathogen interaction? Likewise, the roles of SWEET transporters in response to abiotic stresses are little understood. Here, in addition to their relevance in biotic stress, we also provide a small glimpse of SWEETs importance during plant abiotic stress, and briefly debate their importance in the particular case of grapevine (Vitis vinifera) due to its socioeconomic impact.
Retinal microcirculation abnormalities in patients with systemic sclerosis: an explorative optical coherence tomography angiography study
Authors: Carnevali Adriano , Giannaccare Giuseppe , Gatti Valentina , Battaglia Caterina , Randazzo Giorgio , Yu Angeli Christy , Pellegrini Marco , Ferragina Francesco , Toro Mario Damiano , Bruno Caterina , Scorcia Vincenzo , Ursini Francesco
Published: March 2021

Objectives

To investigate subclinical and clinical abnormalities in retinal and choroidal vascular plexuses in patients with SSc by means of optical coherence tomography angiography (OCT-A).

Methods

A total of 20 consecutive SSc patients were recruited and compared with 20 healthy subjects. Quantitative analysis of vessel density (VD), choriocapillaris plexus flow index (CCP-FI) and choroidal vascularity index were performed on OCT-A images in the superficial capillary plexus (SCP), deep capillary plexus (DCP) and CCP for all patients. Images were further reviewed by two independent readers for the assessment of qualitative abnormalities, including tortuosity, rarefaction areas, megacapillaries and macular-foveal capillaries.

Results

The DCP-VD in the whole scan and in the perifoveal, superior, inferior, nasal and temporal regions was significantly lower in the SSc group. The CCP-FI was significantly higher in SSc patients. When comparing SSc patients with and without digital ulcers, significantly decreased SCP-VD was demonstrated in the whole, perifoveal, superior, inferior, temporal and nasal regions. No difference in any of the OCT-A parameters was observed when comparing patients with and without interstitial lung disease. Qualitative analysis of OCT-A revealed at least one abnormality in 95% of patients.

Conclusion

We showed the ability of OCT-A to disclose early ocular vascular abnormalities in patients with SSc. Our results may represent a hypothesis-generating basis for exploring the potential role of OCT-A in diagnosis, monitoring and prognosis stratification in SSc.
Strangers in the sheets: how Airbnb hosts overcome uncertainty
Authors: Ladegaard Isak
Published: March 2021

Uncertainty is typically viewed as an impediment to trade. I argue that in morally attuned markets, where actors seek not just economic transactions but also social connection, uncertainty contributes to market order and reproduction. Drawing on in-depth interviews with 40 Airbnb hosts, I first explain how market risks are inadequately mitigated by social credit data, that is, publicly available information about exchange partners, and by institutional safeguards, such as the platform’s insurance policy. I then explain how hosts overcome remaining uncertainties by getting to know and building rapport with their guests. This emotional labor is in turn converted to meaningful social relations that motivate further hosting. In some cases, these ad hoc ties transcend the market and live on as authentic friendships.
Use of an electronic medication monitoring device to estimate medication adherence in kidney transplant patients
Authors: Krause Anna Viktoria , Bertram Anna , Nöhre Mariel , Bauer-Hohmann Maximilian , Schiffer Mario , de Zwaan Martina
Published: March 2021

Electronic medication monitoring devices (EMD) have been used as a gold standard for assessing medication adherence. We used a wireless EMD (SimpleMed+), assessed its usability in patients after kidney transplantation (KTx), evaluated adherence, and analyzed concordance with other adherence measures. Fifty-five patients (53% female, mean age 46 years) at least 6 months after KTx agreed to use the EMD over a period of 8 weeks. Self-reported adherence was measured with the BAASIS, and immunosuppressant trough level variability was assessed prior to and again during the study period. Fourteen patients stopped using the EMD or were low users (<70%). These non-completers reported that using the EMD would interfere with their daily activities. Taking-adherence of the completers was high with 98.3% (±1.9) over the entire study period. Timing-adherence was somewhat lower (94.6% ± 7.9) and decreased during the second half of the study. We found statistically significant correlations between EMD results and self-reported adherence with moderate effect sizes, but no significant association with trough level variability. The low usage of the EMD supports the need to assess the practicability of an EMD before applying it in research and clinical routine. Taking- and timing-adherence of KTx patients using the EMD was satisfactory. Self-reported adherence might be a good enough estimate of medication adherence.
Satisfying Clinical and Functional Results in 12 Apert Children Treated With Soft Tissue Distractor
Authors: Winge Mona I. , Røkkum Magne
Published: March 2021

Background:

The complex syndactyly in Apert syndrome hands is challenging to operate. The synostosis and tightness of skin between third and fourth digits lead to severe coverage problems during ray release. A soft tissue distractor can simplify the release with the aim to keep all 10 fingers.

Methods:

A retrospective follow-up of 12 patients/24 hands, median age 8 years (6 to 17 y), 6 boys and 6 girls, operated between 2000 and 2013 was done from 2015 to 2016. The surgical management started with syndactyly release of the first and fourth web, and later of the second. The third stage was placing a soft tissue distractor on the third and fourth finger after osteotomy on the synostosis between them. Four weeks of distraction and 2 weeks of rest resulted in regenerated skin between the digits giving much better coverage of the released digits at time of separation 6 weeks later. Assessment of hand function, grip strength and completion of the Patient Reported Outcome Measure CHEQ was performed.

Results:

Soft tissue coverage at the time of digit separation was considerably facilitated. We experienced 2 infections in 2 hands. In 18/24 hands median 2 (1 to 3) small full thickness skin grafts were needed, usually for coverage of the base of the digits. All wounds healed well. The children managed different practical tasks well, alternating between best functioning grip depending on the activity. According to CHEQ, the children did median 19 (13 to 27) activities independently and median 8 (2 to 15) nonindependently, of a total of 29. Peak strength values for 10/12 children were for the right hand median 17.8% (9.6% to 40.6%) of normative data and for left hand median 13.6% (2.4% to 20.5%) of normative data.

Conclusion:

Soft tissue distraction facilitates the treatment of acrocephalosyndactyly hands, giving 5-fingered hands. Apert children manage many activities independently but struggled with fine motor skills demanding strength.

Level of Evidence:

Level IV evidence.
Pediatric Spinal Cord Injury without Radiographic Abnormality
Authors: Zou Zhewei , Teng Anna , Huang Liuyi , Luo Xiuyuan , Wu Xinhao , Zhang Haocheng , Chen Kinon
Published: March 2021

Study Design.

Retrospective study.

Objective.

To describe the epidemiology and clinical outcomes of pediatric patients with spinal cord injury (SCI) without radiographic abnormality (SCIWORA) in mainland China for the first time.

Summary of Background Data.

SCIWORA is a syndrome that often occurs in children mainly due to the unique biomechanics of the pediatric spine. Although there have been numerous retrospective studies on pediatric SCIWORA, and mainland China has more patients with SCI than anywhere else, pediatric patients with SCIWORA in mainland China has not been described in any study.

Methods.

Review of all cases with SCIWORA at Beijing Children's Hospital between July 2007 and December 2019.

Results.

Of the 189 pediatric patients with SCI 140 had SCIWORA (age: 5.65 ± 2.60 years, male-to-female ratio: 2:5). Main causes of injuries were sports (41%, mostly backbend), falls (27%), traffic accidents (10%), and violence (8%). Lesions were located at the thoracic (77%), cervical (10%), multiple (5%), and lumbar (4%) levels. Incubation period was 2 ± 6 hours. Pathological characteristics of SCI were detected in 96% patients by magnetic resonance imaging (MRI). Based on the American Spinal Injury Association impairment scale (AIS), many patients had complete impairment (50% AIS A, 45% AIS B/C/D, 1% AIS E). Particularly, the five patients with normal MRI tended to have mild injury (AIS D) (P < 0.001), but they still showed abnormal reflex. In the one patient who could not be graded at all by AIS, his only functional deficits were abnormal upper and lower limb muscle tones. A total of 59% patients were treated with methylprednisolone, dexamethasone, or both. Out of 76 patients 59 showed neurological improvement before discharge. The only association among age, cause of injury, level of lesion, incubation period, AIS grade, type of corticosteroid therapy, and neurological improvement was between level of lesion and AIS grade (P < 0.001).

Conclusion.

Demographic and clinical differences exist in patients with SCIWORA. MRI and detailed neurological examinations should both be performed for proper diagnosis. There is still a need to develop better treatment strategy for these patients.

Level of Evidence: 4
The Utility of Prolonged Prophylactic Systemic Antibiotics (PPSA) for Subfascial Drains After Degenerative Spine Surgery
Authors: Pivazyan Gnel , Mualem William , D’Antuono Matthew R. , Dowlati Ehsan , Nair Nathan , Mueller Kyle B.
Published: March 2021

Study Design.

Retrospective cohort study.

Objective.

The aim of the current investigation was to evaluate the impact of prolonged prophylactic systemic antibiotics (PPSA) on the development of surgical site infection rate (SSIR) in degenerative spine surgery.

Summary of Background Data.

Surgical drains are utilized postoperatively in posterior spine surgery to help minimize the risk of seroma formation. Prophylactic antibiotics while drains are in place are frequently used to reduce SSIR, though the practice remains controversial.

Methods.

We performed a single center, retrospective review of all patients that underwent posterior spinal surgery for cervical and lumbar degenerative pathology over a 3.5 year period (January 2016–July 2019). Patients underwent a traditional open posterior midline procedure with postoperative placement of a subfascial surgical drain. Antibiotics were administered for the duration of the drain (PPSA group) or for 24 hours postoperatively (non-PPSA group). The number of surgical site infections, organism, and Clostridium difficile infections was recorded.

Results.

Three hundred thirty six patients were identified, 168 patients in the PPSA group and 168 in the non-PPSA groups. The overall SSIR was 5.36% (18/336). The SSIR for the non-PPSA and PPSA groups were 7.14% (12/168) and 3.57% (6/168), respectively (P = 0.146). While difference of SSIR between the groups was two-fold, it was not statistically significant. For the non-PPSA and PPSA groups, the SSIR for cervical (5.95% [5/84] vs. 2.38% [2/84], P = 0.443) and lumbar (8.33% [7/84], vs. 4.76% [4/84], P = 0.535) regions were not significantly different. C. difficile cases in the PPSA and non-PPSA groups were 1/168 and 0/168 respectively (P = 1.00).

Conclusion.

Our series demonstrate a two-fold reduction of SSI with implementation of PPSA regimen. This benefit was demonstrated separately for both cervical and lumbar regions. Randomized trials and increase in sample size are warranted to elucidate the significance of PPSA in posterior spinal surgery.

Level of Evidence: 3
Kinetic Glomerular Filtration Rate Equations in Patients With Shock: Comparison With the Iohexol-Based Gold-Standard Method
Authors: Desgrouas Maxime , Merdji Hamid , Bretagnol Anne , Barin-Le Guellec Chantal , Halimi Jean-Michel , Ehrmann Stephan , Salmon Gandonnière Charlotte
Published: March 2021

OBJECTIVES:

Static glomerular filtration rate formulas are not suitable for critically ill patients because of nonsteady state glomerular filtration rate and variation in the volume of distribution. Kinetic glomerular filtration rate formulas remain to be evaluated against a gold standard. We assessed the most accurate kinetic glomerular filtration rate formula as compared to iohexol clearance among patients with shock.

DESIGN:

Retrospective multicentric study.

SETTING:

Three French ICUs in tertiary teaching hospitals.

PATIENTS:

Fifty-seven patients within the first 12 hours of shock.

MEASUREMENTS AND MAIN RESULTS:

On day 1, we compared kinetic glomerular filtration rate formulas with iohexol clearance, with or without creatinine concentration correction according to changes in volume of distribution and ideal body weight. We analyzed three static glomerular filtration rate formulas (Cockcroft and Gault, modification of diet in renal disease, and Chronic Kidney Disease–Epidemiology Collaboration), urinary creatinine clearance, and seven kinetic glomerular filtration rate formulas (Jelliffe, Chen, Chiou and Hsu, Moran and Myers, Yashiro, Seelhammer, and Brater). We evaluated 33 variants of these formulas after applying corrective factors. The bias ranged from 12 to 47 mL/min/1.73 m2. Only the Yashiro equation had a lower bias than urinary creatinine clearance before applying corrective factors (15 vs 20 mL/min/1.73 m2). The corrected Moran and Myers formula had the best mean bias, 12 mL/min/1.73 m2, but wide limits of agreement (–50 to 73). The corrected Moran and Myers value was within 30% of iohexol-clearance–measured glomerular filtration rate for 27 patients (47.4%) and was within 10% for nine patients (15.8%); other formulas showed even worse accuracy.

CONCLUSIONS:

Kinetic glomerular filtration rate equations are not accurate enough for glomerular filtration rate estimation in the first hours of shock, when glomerular filtration rate is greatly decreased. They can both under- or overestimate glomerular filtration rate, with a trend to overestimation. Applying corrective factors to creatinine concentration or volume of distribution did not improve accuracy sufficiently to make these formulas reliable. Clinicians should not use kinetic glomerular filtration rate equations to estimate glomerular filtration rate in patients with shock.
A Simulated Prospective Evaluation of a Deep Learning Model for Real-Time Prediction of Clinical Deterioration Among Ward Patients*
Authors: Shah Parth K. , Ginestra Jennifer C. , Ungar Lyle H. , Junker Paul , Rohrbach Jeff I. , Fishman Neil O. , Weissman Gary E.
Published: March 2021

OBJECTIVES:

The National Early Warning Score, Modified Early Warning Score, and quick Sepsis-related Organ Failure Assessment can predict clinical deterioration. These scores exhibit only moderate performance and are often evaluated using aggregated measures over time. A simulated prospective validation strategy that assesses multiple predictions per patient-day would provide the best pragmatic evaluation. We developed a deep recurrent neural network deterioration model and conducted a simulated prospective evaluation.

DESIGN:

Retrospective cohort study.

SETTING:

Four hospitals in Pennsylvania.

PATIENTS:

Inpatient adults discharged between July 1, 2017, and June 30, 2019.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

We trained a deep recurrent neural network and logistic regression model using data from electronic health records to predict hourly the 24-hour composite outcome of transfer to ICU or death. We analyzed 146,446 hospitalizations with 16.75 million patient-hours. The hourly event rate was 1.6% (12,842 transfers or deaths, corresponding to 260,295 patient-hours within the predictive horizon). On a hold-out dataset, the deep recurrent neural network achieved an area under the precision-recall curve of 0.042 (95% CI, 0.04–0.043), comparable with logistic regression model (0.043; 95% CI 0.041 to 0.045), and outperformed National Early Warning Score (0.034; 95% CI, 0.032–0.035), Modified Early Warning Score (0.028; 95% CI, 0.027– 0.03), and quick Sepsis-related Organ Failure Assessment (0.021; 95% CI, 0.021–0.022). For a fixed sensitivity of 50%, the deep recurrent neural network achieved a positive predictive value of 3.4% (95% CI, 3.4–3.5) and outperformed logistic regression model (3.1%; 95% CI 3.1–3.2), National Early Warning Score (2.0%; 95% CI, 2.0–2.0), Modified Early Warning Score (1.5%; 95% CI, 1.5–1.5), and quick Sepsis-related Organ Failure Assessment (1.5%; 95% CI, 1.5–1.5).

CONCLUSIONS:

Commonly used early warning scores for clinical decompensation, along with a logistic regression model and a deep recurrent neural network model, show very poor performance characteristics when assessed using a simulated prospective validation. None of these models may be suitable for real-time deployment.
Coronavirus disease 2019: a comprehensive review and meta-analysis on cardiovascular biomarkers
Authors: Qiang Zhiyi , Wang Bing , Garrett Brenda C. , Rainey R. Patrick , Superko Harold Robert
Published: March 2021

Purpose of review

Preventive cardiology has an important role to play in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The SARS-CoV-2 pandemic has been observed to have a greater mortality impact on subgroups of people in the population who are deemed to be at higher medical disease risk. Individuals with cardiovascular disorders are one such COVID-19-associated high-mortality risk group.

Recent findings

Evidence is accumulating that COVID-19 infection may worsen an individual's future cardiovascular health, and, preinfection/postinfection cardiovascular evaluation may be warranted to determine if progressive cardiovascular damage has occurred because of COVID-19 infection. In this study, we conducted a systematic review and meta-analysis, focusing on the association between COVID-19 severity and cardiac-specific biomarkers, including N-terminal pro-B-type natriuretic peptide (NT-proBNP), troponin T (TnT)/troponin I (TnI), lactate dehydrogenase (LDH), creatine kinase, and creatine kinase isoenzyme (CK-MB). TnT had the highest odds ratio or OR (11.83) indicating the greatest association with COVID-19 severity, followed by NT-proBNP (7.57), TnI (6.32), LDH (4.79), D-dimer (4.10), creatine kinase (3.43), and CK-MB (3.35). All of the biomarkers studied were significantly correlated with COVID-19 severity including severe symptoms, ICU care, and mortality (P < 0.0001, except P < 0.01 for CK-MB).

COVID-19 infection results in short-term and long-term disease risk that may involve adverse cardiovascular health issues including heart failure. Cardiac-specific biomarkers appear to identify a subset of COVID-19 patients who have the highest risk of an adverse medical outcome. Preventive cardiology has an important role to play in the COVID-19 pandemic.

The risk/benefit analysis of maintaining or eliminating the use of the angiotensin receptor blockers (ARB) and angiotensin-converting enzyme inhibitor (ACE-I) medications deserves further investigation.
Prophylaxis With Trimethoprim/Sulfamethoxazole Is Not Necessary in Children With Solid Tumors Treated With Low–medium Intensity Chemotherapy
Authors: Meazza Cristina , Galaverna Federica , Petris Maria Grazia , Zama Daniele , La Spina Milena , Muggeo Paola , Ziino Ottavio , Cellini Monica , Soncini Elena , Barone Angelica , De Santis Raffaella , Perruccio Katia , Mura Rossella , Pascale Silvia , Mercolini Federico , Cesaro Simone
Published: March 2021

Prophylaxis of Pneumocystis jiroveci pneumonia (PJP) with trimethoprim/sulfamethoxazole is a standard of care for children with hematologic malignancies, while its use in solid tumor patients is still debated. A retrospective study focusing on the use of PJP prophylaxis in patients with solid tumors was performed among 16 AIEOP centers: 1046/2863 patients did not receive prophylaxis and no cases of PJP were reported.
Approach to patients with European Network for the Study of Adrenal Tumor stages I and II adrenocortical carcinomas
Authors: Kastelan Darko , Muzurovic Emir , Dusek Tina
Published: March 2021

Purpose of review

Adrenocortical carcinoma (ACC) is a rare tumor with variable prognosis depending mostly on the disease stage and tumor grade. The staging system proposed by the European Network for the Study of Adrenal Tumors has a reliable prognostic potential and defines ACC stages I–IV. Due to the absence of extraadrenal tissue invasion, patients with stage I-II have a lower recurrence rate and better prognosis. This article elaborates on the current understanding of the clinical approach to this group of patients.

Recent findings

Concerning the treatment, complete surgical resection of the tumor provides the only chance for cure. However, even after tumor removal, the risk of recurrence remains high and the main predictors of recurrence include tumor stage, grade (measured by Ki-67 proliferative index), and the tumor resection status. Adjuvant mitotane and/or adjuvant radiotherapy should be considered in patients with high risk of recurrence taking into account potential harmful effects of such treatment. Accordingly, careful selection of patients who may benefit from adjuvant treatment is of the utmost importance both for improving disease outcome and for avoiding potential overtreatment in patients who are at low risk of disease recurrence.

Many aspects of the management of patients with ACC stages I and II are not entirely evidence-based, and treatment decisions rely mostly on expert opinions and data from retrospective studies. Therefore, the treatment of these patients should be restricted to specialized centers with high expertise in ACC.
A Simple and Quick Method for Decalcification Using Mouse Tail as a Model for Preparation of Lymphedema Study
Authors: Yang Duo , Li Sha , Wu Jiangping
Published: March 2021

The disadvantage of 10% EDTA decalcification is a long time-consuming. It needs to identify a quick and straightforward decalcification method when the preparation of lymphedema models using mouse tail which was a sample of bone wrapped in other tissues. In the present study, mouse tail samples were decalcified in 10% EDTA at 25, 37, and 42°C, respectively, with continuous shaking (150 rpm/min). The histologic integrity of samples was evaluated by hematoxylin and eosin staining, and the preservation of antigenicity was tested by either immunohistochemistry or immunofluorescence. The decalcification was distinctly accelerated by temperature. Results of hematoxylin and eosin staining were similar among different temperature groups. Immunohistochemistry and immunofluorescence staining revealed almost no signals in samples decalcified at 42°C for 1 week. Clear signals were detected when samples were decalcified at 37 and 25°C.
To dose-adjust or not to dose-adjust: lamivudine dose in kidney impairment
Authors: Mounzer Karam , Brunet Laurence , Wyatt Christina M. , Fusco Jennifer S. , Vannappagari Vani , Tenorio Allan R. , Shaefer Mark S. , Ragone Leigh , Hsu Ricky K. , Fusco Gregory P.
Published: March 2021

Objectives:

To assess the risk of adverse diagnoses and laboratory abnormalities associated with a 300 or 150 mg daily dose of lamivudine (3TC) initiated by people with HIV (PWH) with an estimated glomerular filtration rate (eGFR) between at least 30 and 49 ml/min per 1.73 m2 or less.

Design:

Longitudinal study based on electronic health records of 539 PWH with eGFR between at least 30 and 49 ml/min per 1.73 m2 or less from the Observational Pharmaco-Epidemiology Research and Analysis (OPERA) cohort.

Methods:

Common unintended effects of 3TC were evaluated as composite outcomes. We estimated the incidence (univariate Poisson regression) and association between dose and incident composite outcomes (multivariate Poisson regression) among PWH without the relevant diagnoses or laboratory abnormalities at 3TC initiation.

Results:

PWH initiating 150 mg 3TC had higher HIV RNA, lower eGFR, and more comorbidities than those initiating 300 mg 3TC. The prevalence of relevant diagnoses and laboratory abnormalities was similar in both groups. The most common lab abnormality was low hemoglobin. There was no statistically significant difference in incident adverse diagnoses/severe lab abnormalities with 300 mg versus 150 mg [incidence rate ratio (IRR): 1.51; 95% confidence interval (CI) 0.59--3.92). However, a statistically significant association was observed when gastrointestinal symptoms/moderate lab abnormalities were included in the outcome (IRR: 3.07, 95% CI 1.12--8.40).

Conclusion:

As 3TC is a well tolerated drug with a wide therapeutic window, dose adjustment may be unnecessary among PWH with eGFR between at least 30 and 49 ml/min per 1.73 m2 or less. Clinical judgement is key when weighing the risks and benefits of 3TC dose adjustment for PWH experiencing gastrointestinal symptoms or moderate lab abnormalities.
Modified Nasoseptal Rescue Flap Technique for Pituitary Adenoma Resection via Endoscopic Endonasal Approach
Authors: Zheng Jiantao , Guo Wenlong , Zhan Shengquan , Zhou Dexiang , Fang Miaoxian , Zhou Dong
Published: March 2021

Nasoseptal rescue flap (NSRF), which preserves the pedicle of the flap and is harvested as a nasoseptal flap (NSF) when intraoperative leakage of cerebrospinal fluid (CSF) occurs, is an alternative strategy for skull base reconstruction in patients with pituitary adenoma resection via an endoscopic endonasal approach. However, in practice, the original NSRF technique cannot meet the needs during operation. Therefore, the authors aimed to describe a modified NSRF technique for the resection of pituitary adenoma via endoscopic endonasal approach and to examine its utility and outcomes. The authors retrospectively analyzed the medical records of 87 consecutive patients with pituitary adenoma who underwent endoscopic endonasal surgery performed using NSRF technique from September 2019 to August 2020. Data on intraoperative CSF leakage, NSF conversion rate, and reconstruction-related complications were analyzed. The average age of patients was 50.1 years (men, 50.5%). Twenty-five cases of intraoperative CSF leakage were observed: 23 cases of low-flow CSF leakage and two cases of high-flow CSF leakage. NSRF was converted to NSF in 11 cases. Two patients experienced postoperative CSF leakage after reconstruction without NSF and required unplanned reoperation to rebuild the skull base with NSF. In conclusion, this modified NSRF utilized a minimally invasive way to provide sufficient surgical corridor without the need for pedicle retraction, and it can be effectively converted to an NSF for skull base reconstruction in patients with pituitary adenoma.
Ovalopodium rosalinum sp. nov., Planopodium haveli gen. nov, sp. nov., Planopodium desertum comb. nov. and new insights into phylogeny of the deeply branching members of the order Himatismenida (Amoebozoa)
Authors: Kudryavtsev Alexander , Völcker Eckhard , Clauß Steffen , Pawlowski Jan
Published: March 2021

The order Himatismenida (Amoebozoa, Discosea) comprises naked amoebae with an organic coat that is located on the dorsal surface of the cell. The phylogenetic relationships among deeply branching genera of the Himatismenida are unclear, as data on the species diversity of the himatismenid genera is largely restricted to the derived genus Cochliopodium. Here, we describe two new amoeba species that branch at the base of the order Himatismenida, evidenced by SSU rRNA gene and multigene analyses. Among them, a freshwater species Planopodium haveli gen. nov., sp. nov. has a dorsal cell coat consisting of flat, oval scales. This species forms a clade at the base of the Himatismenida, and the previously described Ovalopodium desertum, its closest relative, is transferred into the new genus as Planopodium desertum comb. nov. Although the two species are barely distinguishable by their sequence data, they are clearly distinct in morphology. Using this data, we can report the first evidence of a dorsal cell coat consisting of scales outside of the genus Cochliopodium. The other species has a marine origin and branches deeply, close to the root of the phylogenetic tree of Himatismenida. Based on the morphology of this amoeba, it should be described as Ovalopodium rosalinum sp. nov., a new species of the genus Ovalopodium. Analyses of the phylogenetic relationships and the ultrastructure of the deeply branching himatismenids, together with several of the newly obtained gene sequences of Parvamoeba and Cochliopodium, suggest that some elements of the dorsal cell coat of Ovalopodium may be ancestral for Himatismenida and have been partly retained in various more derived species of this clade, in particular, Cochliopodium gallicum. Although actin and Cox1 gene data do not resolve the higher-level relationships in Himatismenida, they correspond to the grouping of species within most genera.
Maximisation of open hospital capacity under shortage of SARS-CoV-2 vaccines
Authors: Bosbach Wolfram A. , Heinrich Martin , Kolisch Rainer , Heiss Christian
Published: March 2021

Motive

The Covid-19 pandemic has led to the novel situation that hospitals must prioritise staff for a vaccine rollout while there is acute shortage of the vaccine. In spite of the availability of guidelines from state agencies, there is partial confusion about what an optimal rollout plan is. This study investigates effects in a hospital model under different rollout schemes.

Methods

A simulation model is implemented in VBA and studied for parameter variation. The implemented code is available as open access supplement.

Main results

A rollout scheme assigning vaccine doses to staff primarily by staff’s pathogen exposure maximises the predicted open hospital capacity when compared to a rollout based on hierarchical prioritisation. The effect increases under resource scarcity and increasing disease activity. Nursing staff benefits most from an exposure focused rollout.

Conclusions

The model employs SARS-CoV-2 parameters; nonetheless, effects observable in the model are transferable to other infectious diseases. Necessary future prioritisation plans need to consider pathogen characteristics and social factors.
Mutation hotspots, geographical and temporal distribution of SARS-CoV-2 lineages in Brazil, February 2020-2021: insights and limitations from uneven sequencing efforts
Authors: Franceschi Vinícius Bonetti , Ferrareze Patrícia Aline Gröhs , Zimerman Ricardo Ariel , Cybis Gabriela Bettella , Thompson Claudia Elizabeth
Published: March 2021

The COVID-19 pandemic has already reached approximately 110 million people and it is associated with 2.5 million deaths worldwide. Brazil is the third worst-hit country, with approximately 10.2 million cases and 250 thousand deaths. International efforts have been established to share information about SARS-CoV-2 epidemiology and evolution. However, sequencing facilities and research investments are very heterogeneous across different regions and countries. The understanding of the SARS-CoV-2 evolution plays a significant role in the development of effective strategies for public health and disease management. We aimed to analyze the available and high-quality genome sequences from Brazil between February 2020 and February 2021 to identify mutation hotspots, geographical and temporal distribution of SARS-CoV-2 lineages by using phylogenetics and phylodynamics analyses. We describe heterogeneous and episodic sequencing efforts, the progression of the different lineages along time, evaluating mutational spectra and frequency oscillations derived from the prevalence of novel and specific lineages across different Brazilian regions. We found at least seven major (1-7) and two minor clades (4.2 and 5.3) related to the six most prevalent lineages in the country and described its spatial distribution and dynamics. The emergence and recent frequency shift of lineages (P.1 and P.2) containing mutations of concern in the spike protein (e. g., E484K, N501Y) draws attention due to their association with immune evasion and enhanced receptor binding affinity. Improvements in genomic surveillance are of paramount importance and should be extended in Brazil to better inform policy makers and enable evidence-based decisions to fight the COVID-19 pandemic.