bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of laboratory procedures on postthawing cell viability and hematopoietic engraftment after autologous peripheral blood stem cell transplantation
Authors: Belisário André Rolim , da Costa Funes Ana Paula , Luz Junio Rocha , de Almeida Costa Luciana , Furtado Marina Dos Santos Brito Silva , Martins Maurício Colombini , Cruz Nathália Gomide , Pederzoli Paula Renata Machado Passos , de Andrade Roberta Kelly , Libânio Marcia Regina Issa Salomão , de Lima Prata Karen
Published: February 2021

Background

The kinetics of hematopoietic recovery after autologous stem cell transplantation (ASCT) may be affected by laboratory procedures. The aim of this study was to evaluate the influence of characteristics of the cryopreserved units of peripheral blood stem cells (PBSC) on postthawing cell viability and engraftment outcomes after ASCT.

Study Design and Methods

This was a retrospective cohort study including individuals referred for ASCT. Cryopreservation was conducted at a single processing facility between 2014 and 2019, and patients received clinical care at six transplant centers. Covariates and outcome data were retrieved from participants’ records.

Results

The study population comprised 619 patients (345 [55.7%] male). Median age was 53 years. Multiple myeloma was the most common diagnosis (62.7%). Higher preapheresis CD34+ cell count, lower nucleated cell (NC) concentration per cryobag, and composition of the cryoprotectant solution (5% dimethyl sulfoxide [DMSO] and 6% hydroxyethyl starch) were statistically significantly associated with higher postthawing cell viability. The linear regression model for time to neutrophil and platelet engraftment included the infused CD34+ cell dose and the composition of the cryoprotectant solution. Patients who had PBSC cryopreserved using 10% DMSO solution presented six times higher odds (odds ratio [OR] = 6.9; 95% confidence interval [CI]: 2.2‐21.1; p = .001) of delayed neutrophil engraftment (>14 days) and two times higher odds (OR = 2.3, 95%CI: 1.4‐3.7; p = .001) of prolonged hospitalization (>18 days).

Discussion

The study showed that mobilization efficacy, NC concentration, and the composition of the cryoprotectant solution significantly affected postthawing cell viability. In addition, the composition of the cryoprotectant solution significantly impacted engraftment outcomes and time of hospitalization after ASCT.
Single‐leg exercise training augments in vivo skeletal muscle oxidative flux and vascular content and function in adults with type 2 diabetes
Authors: Scalzo Rebecca L. , Schauer Irene E. , Rafferty Deirdre , Knaub Leslie A. , Kvaratskhelia Nina , Johnson Taro Kaelix , Pott Gregory B. , Abushamat Layla A. , Whipple Mary O. , Huebschmann Amy G. , Cree‐Green Melanie , Reusch Jane E. B. , Regensteiner Judith G.
Published: February 2021

Key points

People with type 2 diabetes (T2D) have impaired skeletal muscle oxidative flux due to limited oxygen delivery.

In the current study, this impairment in oxidative flux in people with T2D was abrogated with a single‐leg exercise training protocol.

Additionally, single‐leg exercise training increased skeletal muscle CD31 content, calf blood flow and state 4 mitochondrial respiration in all participants.

Cardiorespiratory fitness is impaired in type 2 diabetes (T2D), conferring significant cardiovascular risk in this population; interventions are needed. Previously, we reported that a T2D‐associated decrement in skeletal muscle oxidative flux is ameliorated with acute use of supplemental oxygen, suggesting that skeletal muscle oxygenation is rate‐limiting to in vivo mitochondrial oxidative flux during exercise in T2D. We hypothesized that single‐leg exercise training (SLET) would improve the T2D‐specific impairment in in vivo mitochondrial oxidative flux during exercise. Adults with (n = 19) and without T2D (n = 22) with similar body mass indexes and levels of physical activity participated in two weeks of SLET. Following SLET, in vivo oxidative flux measured by 31P‐MRS increased in participants with T2D, but not people without T2D, measured by the increase in initial phosphocreatine synthesis (P = 0.0455 for the group × exercise interaction) and maximum rate of oxidative ATP synthesis (P = 0.0286 for the interaction). Additionally, oxidative phosphorylation increased in all participants with SLET (P = 0.0209). After SLET, there was no effect of supplemental oxygen on any of the in vivo oxidative flux measurements in either group (P > 0.02), consistent with resolution of the T2D‐associated oxygen limitation previously observed at baseline in subjects with T2D. State 4 mitochondrial respiration also improved in muscle fibres ex vivo. Skeletal muscle vasculature content and calf blood flow increased in all participants with SLET (P < 0.0040); oxygen extraction in the calf increased only in T2D (P = 0.0461). SLET resolves the T2D‐associated impairment of skeletal muscle in vivo mitochondrial oxidative flux potentially through improved effective blood flow/oxygen delivery.
Active Catalogs: Integrated Support for Component Engineering
Authors: Coutinho Murilo , Eleish Ragy , Kim Jihie , Kumar Vished , Ling S. Ringo , Neches Robert , Will Peter
Published: February 2021

A recent National Academy of Sciences study shows that design and manufacturing is dominated by three “eighty percent” rules. Eighty percent of the cost of a product typically is the purchase cost of its components. Eighty percent of the manufacturing costs are determined in the first twenty percent of the design phase. And eighty percent of an engineer’s time is spent not on design, but on communications: obtaining information about components comprising the design and coordinating with other engineers about design issues. Thus, the speed and quality of product development is heavily dependent on a designer’s ability to perform component engineering — to configure a set of components that work well together with respect to performance, reliability, cost and delivery schedule. This paper describes services provided in the Active Catalogs system that support the component engineering process. These services enable a designer not only to find candidate parts to serve as individual components in a design, but to explore and assess interactions between candidate parts for sets of components. These services include mechanisms for: (1) creating queries for parts based on their intended use rather than merely parametric specifications; (2) refining those queries to take account of constraints imposed by other components; (3) providing multi-modal information to help designers assess and compare candidate parts; and (4) generating simulation models of candidate parts and integrating them to provide simulation models of candidate systems.
A Web-Based Framework for Design and Manufacturing a Mechanical System
Authors: Chung Moon Jung , Keyes Dave , Choi Young K. , Kwon Patrick , Gu Hua , Behr Markus
Published: February 2021

For industries to gain competitiveness in a global market, an infrastructure is necessary that efficiently coordinates a variety of design and manufacturing activities taking place simultaneously as well as sequentially at distant locations. We propose a web-based engineering framework for such infrastructure, which integrates various advanced design/manufacturing systems such as CAD, FEM and CAM, provides relationships among product data, and coordinates with manufacturing processes. This paper demonstrates the current capability of our framework with a benchmark study on a gearbox. Designers can access the framework through the WWW browser and start the design with a set of requirements such as the required torque and gear reduction ratio. Using the Common Gateway Interface (CGI) to execute the various tools distributed on the networks, the framework autonomously performs a sequence of engineering analysis and searches for a set of components that meets the overall requirement of our design. The framework also integrates the design results with manufacturing processes by selecting appropriate cutting tools, machining conditions, sequence of operations and surface finish. During the design process, designers can check the design results ranging from the graphical display of our design to the CNC code to machine designed shafts that are generated by the framework.
Preparation of a Virtual Proving Ground for Construction Equipment Simulation
Authors: Grant Peter , Freeman Jeffrey S. , Vail Rob , Huck Frank
Published: February 2021

A multi-phased evaluation of the Iowa Driving Simulator as a virtual proving ground for construction equipment simulation is presented. In Phase I the Iowa Driving Simulator was evaluated in an “open-loop” mode to assess its capability to simulate a typical maneuver common to wheel loader operation, and its viability as a test platform for human subject evaluation of those maneuvers.

A typical wheel loader truck loading cycle involves numerous directional shifts. Cycle productivity is increased if these shifts are executed at full engine throttle. Jerk and acceleration levels associated with full throttle shifts, however, can cause both operator discomfort and spillage of loaded material. Electronically controlled transmissions have the potential to both minimize directional shift times and material loss while optimizing operator comfort. This optimization will require an understanding of the factors which affect operator comfort during shifts. A study was therefore devised to determine those aspects of the motion generated by a directional shift which affect operator comfort. The Iowa Driving Simulator motion system was used to present operators with a series of acceleration time histories which are representative of various shift strategies. The operators rated the relative comfort of each strategy during paired comparison tests. Limitations of the simulator motion system prevented definitive results from being drawn; however, results did confirm shift comfort criteria previously established by the machine manufacturer. Success of the Phase I effort was sufficient to warrant a more in-depth study.

In Phase II a complete VPG environment for wheel loader operation on the IDS was developed and qualitatively evaluated. This VPG environment included a visual model of a mine pit, developed for Caterpillar, Inc. by engineers at its National Center for Supercomputing Applications office, combined with the immersive motion capability of the Iowa Driving Simulator. A real-time dynamics model of a generic wheel loader along with a menu driven interface to the data set used to simulate a particular wheel loader were developed at Center for Computer Aided Design. This combination of programs allows changes to the design of a loader to be rapidly evaluated within a virtual proving ground environment or off-line at an engineering workstation. The machine model was then combined with an implement/soil interaction model, also developed at Caterpillar’s National Center for Supercomputing Applications office. The resulting machine model can be evaluated either off-line at a workstation or driven in response to operator input within the Iowa Driving Simulator virtual proving ground environment. A comparison of the offline model’s predictions of machine response to swept-sinewave steering input is shown to compare favorably with measured performance of the actual machine.
From diffusive mass transfer in Stokes flow to low Reynolds number Marangoni boats
Authors: Ender Hendrik , Kierfeld Jan
Published: February 2021

We present a theory for the self-propulsion of symmetric, half-spherical Marangoni boats (soap or camphor boats) at low Reynolds numbers. Propulsion is generated by release (diffusive emission or dissolution) of water-soluble surfactant molecules, which modulate the air–water interfacial tension. Propulsion either requires asymmetric release or spontaneous symmetry breaking by coupling to advection for a perfectly symmetrical swimmer. We study the diffusion–advection problem for a sphere in Stokes flow analytically and numerically both for constant concentration and constant flux boundary conditions. We derive novel results for concentration profiles under constant flux boundary conditions and for the Nusselt number (the dimensionless ratio of total emitted flux and diffusive flux). Based on these results, we analyze the Marangoni boat for small Marangoni propulsion (low Peclet number) and show that two swimming regimes exist, a diffusive regime at low velocities and an advection-dominated regime at high swimmer velocities. We describe both the limit of large Marangoni propulsion (high Peclet number) and the effects from evaporation by approximative analytical theories. The swimming velocity is determined by force balance, and we obtain a general expression for the Marangoni forces, which comprises both direct Marangoni forces from the surface tension gradient along the air–water–swimmer contact line and Marangoni flow forces. We unravel whether the Marangoni flow contribution is exerting a forward or backward force during propulsion. Our main result is the relation between Peclet number and swimming velocity. Spontaneous symmetry breaking and, thus, swimming occur for a perfectly symmetrical swimmer above a critical Peclet number, which becomes small for large system sizes. We find a supercritical swimming bifurcation for a symmetric swimmer and an avoided bifurcation in the presence of an asymmetry.

Graphic abstract
Clinical and Translational Implications of an Emerging Developmental Substructure for Autism
Authors: Constantino John N. , Charman Tony , Jones Emily J.H.
Published: February 2021

A vast share of the population-attributable risk for autism relates to inherited polygenic risk. A growing number of studies in the past five years have indicated that inherited susceptibility may operate through a finite number of early developmental liabilities that, in various permutations and combinations, jointly predict familial recurrence of the convergent syndrome of social communication disability that defines the condition. Here, we synthesize this body of research to derive evidence for a novel developmental substructure for autism, which has profound implications for ongoing discovery efforts to elucidate its neurobiological causes, and to inform future clinical and biomarker studies, early interventions, and personalized approaches to therapy.
Control of RNA Stability in Immunity
Authors: Akira Shizuo , Maeda Kazuhiko
Published: February 2021

Posttranscriptional control of mRNA regulates various biological processes, including inflammatory and immune responses. RNA-binding proteins (RBPs) bind cis-regulatory elements in the 3′ untranslated regions (UTRs) of mRNA and regulate mRNA turnover and translation. In particular, eight RBPs (TTP, AUF1, KSRP, TIA-1/TIAR, Roquin, Regnase, HuR, and Arid5a) have been extensively studied and are key posttranscriptional regulators of inflammation and immune responses. These RBPs sometimes collaboratively or competitively bind the same target mRNA to enhance or dampen regulatory activities. These RBPs can also bind their own 3′ UTRs to negatively or positively regulate their expression. Both upstream signaling pathways and microRNA regulation shape the interactions between RBPs and target RNA. Dysregulation of RBPs results in chronic inflammation and autoimmunity. Here, we summarize the functional roles of these eight RBPs in immunity and their associated diseases.
Lactate and Bilirubin Index: A New Indicator to Predict Critically Ill Cirrhotic Patients’ Prognosis
Authors: Chen Xiao-Fu , Zhao Yuan , Chen Wei-Zhen , Shao Xin-Tian , Huang Zhi-Ming
Published: February 2021

Objectives. We aimed to perform external validation of the prognostic value of the lactate and bilirubin (LB) index, a new indicator, and compare the ability of the LB index and other scoring systems to predict both short- and long-term mortality in critically ill cirrhotic patients. Materials and Methods. A number of 479 cirrhotic patients admitted into ICU were included in our research. We measured prognostic scores in the first 24 hours including LB index, Child–Pugh, SOFA, CLIF-SOFA, and MELD scores. The LB index was calculated as follows: ln [1000 × lactate (mmol/L) × bilirubin (µmol/L)]/2. The primary outcomes were 28-day and 3-year all-cause mortality. Multivariate logistic regression analyses were used to investigate the independent association between the LB index and the mortality in critically ill cirrhotic patients. The area under the receiver operating characteristic curve was used to assess the prediction accuracy of short- and long-term mortality of the clinical score. Calibration of the score was evaluated by Hosmer–Lemeshow goodness-of-fit test for significance. Results. Multivariate logistic regression analysis identified that the LB index (odds ratio: 5.487, 95% confidence interval: 3.542–8.501,

P
<
0.001

) was the strongest predictor for 28-day mortality. The LB index gave the highest area under the curve (0.791, 95% confidence interval: 0.747–0.836) in predicting 28-day mortality. For predicting 3-year mortality, the model for end-stage liver disease (MELD) score showed better discrimination ability with an area under the curve of 0.726 (95% confidence interval: 0.680–0.771). The risk of mortality significantly increased when the clinical scores were ≥ the optimal cutoff values. Conclusions. The LB index, a simple prognostic indicator, performs well in predicting critically ill cirrhotic patients’ short-term prognosis, while, for long-term prognosis, the MELD score is more appropriate.
Duplication of the Gallbladder as an Operative Surprise: A Case Report with Review of the Literature
Authors: Singh Jai P.
Published: February 2021

Introduction. Duplication of the gallbladder is a rare congenital anomaly of the biliary system. Anomalous anatomy of the biliary system is associated with an increased risk of complications such as bile duct injury during cholecystectomy. Herein, I present a case report of duplication of the gallbladder, which was an operative surprise as the patient’s preoperative workup did not reveal any evidence of duplication of the gallbladder. Case Report. A 60-year-old female was admitted for management of recurrent pancreatitis. Diagnosis of biliary pancreatitis was made as her CT and US revealed cholelithiasis. During laparoscopic cholecystectomy, she was found to have duplication of the gallbladder, which was a surgical surprise. Both the gallbladders were successfully removed, and the patient had an uneventful postoperative course. Conclusion. Duplication of the gallbladder is a rare congenital anomaly, which could be associated with other congenital anomalies of the bile duct and vascular system. Extreme care should be taken during cholecystectomy as these anomalies could lead to serious injury to the bile duct and vessels.
Serum Levels of BDNF in Patients with Adenoma and Colorectal Cancer
Authors: Wang Zhe , Wang Shuang , Liu Yu , Gao Shan , Yu Yunqing , Hu Zhaolan
Published: February 2021

The present study is aimed at examining the serum levels of brain-derived neurotrophic factor (BDNF) and investigating its role in differential diagnosis of colorectal cancer (CRC). Materials and Methods. In a Chinese population, we conducted a case-control study to compare the diagnostic performance of serum levels of BDNF and carcinoembryonic antigen (CEA) for CRC. We enrolled 61 healthy controls, 31 patients with adenomas, and 81 patients with CRC. We explored the correlation between serum levels of BDNF and several pathological features, such as tumor differentiation and TNM staging. Results. The serum levels of BDNF were significantly (

p
<
0.0001

) higher in patients with CRC (

10.64
±
3.84

,

n
=
81

) than in the healthy controls (

4.69
±
1.69
 
ng
/
mL

,

n
=
61

). Serum BDNF also correlated with tumor size, tumor differentiation, and TNM staging (

p
<
0.05

). For early diagnosis, the combination of BDNF (AUC 0.719; 95% CI, 0.621–0.816) and CEA (AUC 0.733; 95% CI, 0.632–0.909) slightly improved the diagnostic performance for CRC (AUC 0.823; 95% CI, 0.737-0.909). Conclusions. Combined detection of serum BDNF and CEA may thus have the potential to become a new laboratory method for the early clinical diagnosis of CRC.
Carotid Intraplaque Neovascularization Predicts Ischemic Stroke Recurrence in Patients with Carotid Atherosclerosis
Authors: Song Yan , Dang Ying , Wang Jichang , Cai Hui , Feng Jun , Zhang Hongmei , Ruan Litao
Published: February 2021

Introduction: This study aimed to examine whether intraplaque neovascularization (IPN) of carotid plaques, as characterized by contrast-enhanced ultrasound (CEUS), is associated with ischemic stroke recurrence in patients with carotid atherosclerosis. Methods: We conducted a prospective study of consecutive patients with a recent stroke and at least one atherosclerotic plaque in the carotid artery on the side consistent with symptoms. All patients underwent CEUS after their first admission. IPN was graded on the basis of the presence and location of microbubbles within each plaque. Results: We eventually included 155 patients, all of whom underwent IPN analysis. After a follow-up of 24 months, we recorded 25 (16.1%) stroke recurrences in the whole population. All the recurrences occurred in patients presenting IPN. There was significant difference in the IPN between the 2 groups (p = 0.002). In the final Cox proportional-hazards multivariable models, IPN of grade 2 was independently associated with the risk of stroke recurrence (HR = 4.535; 95% CI: 1.892–10.870; p = 0.001). This association remained after adjusting for the degree of carotid stenosis (HR = 3.491; 95% CI: 1.410–8.646; p = 0.007). Conclusions: IPN was an independent predictor of stroke recurrence in patients with a recent ischemic stroke and carotid atherosclerosis. In predicting stroke recurrence, IPN may be an earlier indicator than carotid stenosis and may help stratify the risk of stroke recurrence.
Patient-Reported Outcomes of Split-Thickness Skin Grafts for Floor of Mouth Cancer Reconstruction
Authors: Larson Andrew R. , Han Mary , Webb Katherine L. , Ochoa Edgar , Stanford-Moore Gaelen , El-Sayed Ivan H. , George Jonathan R. , Ha Patrick K. , Heaton Chase M. , Ryan William R.
Published: February 2021

Introduction: Patient-reported outcome measures (PROM) on quality of life (QOL) for early-stage floor of mouth carcinoma (FOM-CA) undergoing surgical resection and split-thickness skin graft (STSG) reconstruction have not been established. We have performed a cross-sectional QOL analysis of such patients to define functional postoperative outcomes. Methods: Patients with pathologic stage T1/T2 FOM-CA who underwent resection and STSG reconstruction at a tertiary academic cancer center reported outcomes with the University of Washington QOL (v4) questionnaire after at least 6 months since surgery. Results: Twenty-four out of 49 eligible patients completed questionnaires with a mean follow-up of 41 months (range: 6–88). Subsites of tumor involvement/resection included the following: (1) lateral FOM (L-FOM) (n = 17), (2) anterior FOM (A-FOM) (n = 4), and (3) alveolar ridge with FOM, all of whom underwent lateral marginal mandibulectomy (MM-FOM) (n = 3). All patients reported swallowing scores of 70 (“I cannot swallow certain solid foods”) or better. Ninety-six percent (23/24) reported speech of 70 (“difficulty saying some words, but I can be understood over the phone”) or better. A-FOM patients reported worse chewing than L-FOM patients (mean: 50.0 vs. 85.3; p = 0.01). All 4 A-FOM patients reported a low chewing score of 50 (“I can eat soft solids but cannot chew some foods”). Otherwise, there were no significant differences between subsite groups in swallowing, speech, or taste. Conclusion: STSG reconstructions for pathologic T1–T2 FOM-CA appear to result in acceptable PROM QOL outcomes with the exception of A-FOM tumors having worse chewing outcomes.
Patent Foramen Ovale Closure among Patients with Hypercoagulable States Maintained on Antithrombotic Therapy
Authors: Buber Jonathan , Guetta Victor , Orion David , Lubetsky Aharon , Borik Sharon , Vatury Ori , Israel Ariel
Published: February 2021

Background: Percutaneous device closure was shown to effectively prevent recurrent strokes in patients with patent foramen ovale (PFO). Whether this protective effect is relevant for patients with hypercoagulable states (HCSs) is unknown as they were not represented in prior studies. Methods: Data on 136 consecutive patients with a PFO and clinically significant HCS were retrospectively collected. PFO closure and antithrombotic regimen were decided on an individual basis by the treating physicians, and adherence to therapy was routinely evaluated. The outcome was the occurrence of cerebrovascular accident (CVA) or transient ischemic attack (TIA). Results: HCS types consisted of antiphospholipid syndrome (31%), factor-5 Leiden mutation (22%), prothrombin mutation (18%), protein S deficiency (15%), protein C deficiency (7%), methyl-tetra-hydro folate reductase mutation (5%), and essential thrombocytosis (2%). 102 patients (75%) were maintained on anticoagulants and the remaining on antiplatelet therapy. PFO closure was undertaken in 85 (63%); antithrombotic therapy was not interrupted prior to or after the procedures. At a mean follow-up of 46 ± 8 months, 23 patients (17%; 95% confidence interval, 9.3–22%) experienced an outcome event, mainly in the form of CVAs (n = 15, 65%). In multivariable analysis, PFO closure was associated with a 5-fold decrease in the risk of CVA/TIA (p = 0.02). This effect was independent of the type of HCS or antithrombotic therapy. Conclusions: Among patients with HCSs maintained on anticoagulant or antiplatelet therapies, PFO closure was associated with a significantly lower risk of CVA or TIA.
Tubed Temporalis Fascia for Nasal Dorsal Contouring: A Novel Technique
Authors: Hudise Jibril Y. , Aldhabaan Saud A. , Alqabbani Almaha A. , Nassar Raad S. , Alarfaj Ahmed M.
Published: February 2021

Introduction: Nasal dorsum irregularities may occur after nasal trauma or as a postrhinoplasty complication. Here, we present a novel technique using temporalis fascia (TF) grafting for primary and revision rhinoplasty to repair the nasal dorsum, hide nasal irregularities, and improve nasal contouring. Methods: This prospective cohort study was conducted from January 2019 to June 2019 and evaluated nasal dorsal contouring using the TF in a tubed form. The outcome variables were patient satisfaction, dorsal irregularity, and contour definition. The predictor variable was the use of tubed TF for dorsal augmentation. Other associated variables were age, sex, indication for surgery, surgery type, and graft size. Patient satisfaction was evaluated using the Rhinoplasty Outcome Evaluation questionnaire. A rhinoplasty specialist other than the surgeon who performed the procedure evaluated the dorsal augmentation outcomes by inspection and palpation of the dorsum. All statistical analyses were performed using the SPSS software. Results: Seventy-four patients (21.6% men and 78.4% women) were treated with the tubed TF. The mean age was 28.97 years. Thin skin was the most common indication (48.6%) for using TF. The graft size was 2–5 cm; inspection and palpation revealed no irregularities. No reception site complications occurred. One patient had a mild hematoma at the donor site. The mean patient satisfaction score was 10.14 preoperatively and 19.95 postoperatively (p = 0.001). Discussion/Conclusions: Our novel technique of using the TF graft in a tubed form was easy to perform. Furthermore, the tubed TF covers all irregularities, is good for dorsal augmentation, and improves dorsal contouring and definition.
Colchicine for Left Ventricular Infarct Size Reduction in Acute Myocardial Infarction: A Phase II, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Study Protocol – The COVERT-MI Study
Authors: Bresson Didier , Roubille François , Prieur Cyril , Biere Loic , Ivanes Fabrice , Bouleti Claire , Dubreuil Olivier , Rioufol Gilles , Boutitie Florent , Sideris Georges , Elbaz Meyer , Bochaton Thomas , De Bourguignon Charles , El Jonhy Naoual , Dufay Nathalie , Dhelens Carole , Croisille Pierre , Prunier Fabrice , Angoulvant Denis , Ovize Michel , Maucort-Boulch Delphine , Mewton Nathan
Published: February 2021

Inflammatory processes have been identified as key mediators of ischemia-reperfusion injury in ST-segment elevation myocardial infarction (STEMI). They add damage to the myocardium and are associated with clinical adverse events (heart failure and cardiovascular death) and poor myocardial recovery. Colchicine is a well-known alkaloid with potent anti-inflammatory properties. In a proof-of-concept phase II trial, colchicine has been associated with a significant 50% reduction of infarct size (assessed by creatine kinase levels) in comparison to placebo in acute STEMI patients referred for primary percutaneous coronary intervention (PPCI). The Colchicine in STEMI Patients Study (COVERT-MI) is an ongoing confirmative prospective, multicenter, randomized, double-blind trial testing whether a short course oral treatment with colchicine versus placebo decreases myocardial injury in patients presenting with STEMI referred for PPCI. Adult patients, with a first STEMI episode and an initial TIMI flow ≤1, referred for PPCI, will be randomized (n = 194) in a 1:1 ratio to receive an oral bolus of colchicine of 2 mg followed by 0.5 mg b.i.d. treatment during 5 days or matching placebo. The primary endpoint will be the reduction in infarct size as assessed by cardiac magnetic resonance at 5 ± 2 days between both groups. The main secondary endpoints will be tested between groups in hierarchical order with left ventricular ejection fraction at 5 days, microvascular obstruction presence at 5 days, and absolute adverse left ventricular remodeling between 5 days and 3 months. This academic study is being financed by a grant from the French Ministry of Health (PHRCN-16-0357). Results from this study will contribute to a better understanding of the complex pathophysiology underlying myocardial injury after STEMI. The present study describes the rationale, design, and methods of the trial.
Challenges of Adjusting Single-Nucleotide Polymorphism Effect Sizes for Linkage Disequilibrium
Authors: Escott-Price Valentina , Schmidt Karl Michael
Published: February 2021

Background: Genome-wide association studies (GWAS) were successful in identifying SNPs showing association with disease, but their individual effect sizes are small and require large sample sizes to achieve statistical significance. Methods of post-GWAS analysis, including gene-based, gene-set and polygenic risk scores, combine the SNP effect sizes in an attempt to boost the power of the analyses. To avoid giving undue weight to SNPs in linkage disequilibrium (LD), the LD needs to be taken into account in these analyses. Objectives: We review methods that attempt to adjust the effect sizes (β-coefficients) of summary statistics, instead of simple LD pruning. Methods: We subject LD adjustment approaches to a mathematical analysis, recognising Tikhonov regularisation as a framework for comparison. Results: Observing the similarity of the processes involved with the more straightforward Tikhonov-regularised ordinary least squares estimate for multivariate regression coefficients, we note that current methods based on a Bayesian model for the effect sizes effectively provide an implicit choice of the regularisation parameter, which is convenient, but at the price of reduced transparency and, especially in smaller LD blocks, a risk of incomplete LD correction. Conclusions: There is no simple answer to the question which method is best, but where interpretability of the LD adjustment is essential, as in research aiming at identifying the genomic aetiology of disorders, our study suggests that a more direct choice of mild regularisation in the correction of effect sizes may be preferable.
Open Fetal Microneurosurgery for Intrauterine Spina Bifida Repair
Authors: Cruz-Martínez Rogelio , Chavelas-Ochoa Felipe , Martínez-Rodríguez Miguel , Aguilar-Vidales Karla , Gámez-Varela Alma , Luna-García Jonahtan , López-Briones Hugo , Chávez-Vega Joel , Pérez-Calatayud Ángel Augusto , Díaz-Carrillo Manuel Alejandro , Ahumada-Angulo Edgar , Castelo-Vargas Andrea , Chávez-González Eréndira , Juárez-Martínez Israel , Villalobos-Gómez Rosa , Rebolledo-Fernández Carlos
Published: February 2021

Objectives: The aim of the study was to describe the feasibility of open fetal microneurosurgery for intrauterine spina bifida (SB) repair and to compare perinatal outcomes with cases managed using the classic open fetal surgery technique. Methods: In this study, we selected a cohort of consecutive fetuses with isolated open SB referred to our fetal surgery center in Queretaro, Mexico, during a 3.5-year period (2016–2020). SB repair was performed by either classic open surgery (6- to 8-cm hysterotomy with leakage of amniotic fluid, which was replaced before uterine closure) or open microneurosurgery, which is a novel technique characterized by a 15- to 20-mm hysterotomy diameter, reduced fetal manipulation by fixing the fetal back, and maintenance of normal amniotic fluid and uterine volume during the whole surgery. Perinatal outcomes of cases operated with the classic open fetal surgery technique and open microneurosurgery were compared. Results: Intrauterine SB repair with a complete 3-layer correction was successfully performed in 60 cases either by classic open fetal surgery (n = 13) or open microneurosurgery (n = 47). No significant differences were observed in gestational age (GA) at fetal intervention (25.4 vs. 25.1 weeks, p = 0.38) or surgical times (107 vs. 120 min, p = 0.15) between both groups. The group with open microneurosurgery showed a significantly lower rate of oligohydramnios (0 vs. 15.4%, p = 0.01), preterm rupture of the membranes (19.0 vs. 53.8%, p = 0.01), higher GA at birth (35.1 vs. 32.7 weeks, p = 0.03), lower rate of preterm delivery <34 weeks (21.4 vs. 61.5%, p = 0.01), and lower rate of perinatal death (4.8 vs. 23.1%, p = 0.04) than the group with classic open surgery. During infant follow-up, the rate of hydrocephalus requiring ventriculoperitoneal shunting was similar between both groups (7.5 vs. 20%, p = 0.24). All patients showed an intact hysterotomy site at delivery. Conclusion: Intrauterine spina repair by open fetal microneurosurgery is feasible and was associated with better perinatal outcomes than classic open fetal surgery.
Orofacial Granulomatosis and Crohn Disease: Coincidence or Pattern? A Systematic Review
Authors: Gavioli Camila Fátima Biancardi , Florezi Giovanna Piacenza , Dabronzo Maria Luiza Ducati , Jiménez Marcela Ricaurte , Nico Marcello Menta Simonsen , Lourenço Silvia Vanessa
Published: February 2021

Background: To systematically review all cases of orofacial granulomatosis (OFG) and evaluate the association between OFG and Crohn disease (CD). Summary: This review was conducted according to PRISMA guidelines and a search of the PubMed, MEDLINE, and Embase databases, and the Cochrane Library in March 2020, using keywords and MeSH terms associated with “orofacial granulomatosis,” “Crohn disease,” and their variants, with no language restrictions and across all age groups. All relevant articles were accessed in full text. Single case reports and articles on sarcoidosis, allergy, ulcerative colitis, and infectious diseases were excluded from the analysis. Results: We retrieved 507 reports on OFG. The mean age at onset was 23.3 years (range 2–89 years). A total of 240 (47.3%) females and 267 (52.6%) males were included. CD was present in 93 children aged <16 years (68.3%) and in 43 adults (31.9%). In most cases, the OFG appeared before the CD. The most common clinical manifestations were intraoral mucosa abnormalities (n = 251; 49.5%), lower-lip swelling (n = 249; 49.1%), upper-lip swelling (n = 227; 44.7%), and gingivae (n = 193; 38.7%). Patients with concurrent CD were more likely to experience involvement of the buccal sulcus. Key Messages: OFG presents primarily as a solo entity. The OFG that was associated with CD was present in 93 children aged under 16 years (68.3%) and in 43 adults (31.9%). Childhood onset of OFG carries with it a higher risk of developing CD.
Concurrent Validity of the ABC Dementia Scale with Other Standard Scales: A New Comprehensive Instrument for Assessing Dementia in Japan
Authors: Shimoda Wataru , Murata Jun , Nakatani Akira , Satoh Katsuya
Published: February 2021

Background/Aims: The ABC Dementia Scale (ABC-DS), a new tool for evaluating dementia, was developed in Japan. The ABC-DS is a comprehensive instrument that can simultaneously evaluate activities of daily living (ADLs), behavioral and psychological symptoms of dementia (BPSD), and cognitive function. The ABC-DS can be administered easily and quickly and can clarify the severity of dementia and its changes over time. While the ABC-DS has been reported to be useful in Alzheimer disease (AD)-type dementia, it has not yet been studied in other types of dementia. The purpose of this study was to reevaluate the standard validity of ABC-DS separately for various dementia types and severities. Methods: We evaluated the ABC-DS in outpatients at 1 hospital in Nagasaki Prefecture and patients who use the facility. Domain A, corresponding to ADLs, correlated with Disability Assessment for Dementia (DAD); domain B, corresponding to BPSD, correlated with the Neuropsychiatric Inventory (NPI); domain C, corresponding to cognitive functions, correlated with Mini-Mental State Examination (MMSE); and the total score of the ABC-DS correlated with the Clinical Dementia Rating (CDR). Results: 102 patients, comprising 38 males and 64 females with an average age of 80.7 ± 8.6 years, were enrolled. AD-type dementia was present in 38 cases, vascular dementia (VaD) in 23, mixed dementia in 23, dementia with Lewy bodies in 6, argyrophilic grain dementia in 9, and mild cognitive impairment in 3. A strong correlation was found between ABC-DS domain scores and their respective reference neuropsychological instruments (domain A and the DAD, domain B and the NPI, domain C and the MMSE, and total score and CDR). The correlation of each ABC-DS domain score with the corresponding standard scale depended on the type and severity of dementia, and we observed moderate or high correlations in AD and VaD patients with moderate and severe dementia. Discussion: Although the ABC-DS targets AD, it can be used in VaD based on the results of this study. In other types of dementia, the results differed depending on the domain; in some conditions, the ABC-DS may not show sufficient concurrent validity with other standard scales. Also, the ABC-DS is more beneficial for moderate-to-severe dementia, as reported in previous studies. It is highly useful in clinical practice in Japan since there more than half of all patients have moderate-to-severe dementia.
The Impact of ANxA6 Gene Polymorphism on the Efficacy of Methotrexate Treatment in Psoriasis Patients
Authors: Fan Zhijia , Zhang Zhenghua , Huang Qiong , Han Ling , Fang Xu , Yang Ke , Wu Siyuan , Zheng Zhizhong , Yawalkar Nikhil , Wang Zhicheng , Yan Kexiang
Published: February 2021

Background: There are great interindividual variations in the clinical efficacy of methotrexate (MTX) treatment and patients’ genetic background seems promising in its explanation. Objectives: The study aimed to test whether the polymorphism of annexin A6 (ANxA6) gene, a susceptibility factor for psoriasis, was associated with the clinical response to MTX therapy. Methods: A total of 325 patients enrolled in the study received oral MTX treatment, of whom 310 completed the 1-year study and performed the genotype analysis. They were defined as responders (a reduction of Psoriasis Area and Severity Index [PASI] score ≥75%) and nonresponders (a reduction of PASI <50%) compared to baseline after 12 weeks of short-time therapy. On 1-year treatment, they were defined as responders if they achieved PASI75 and absolute PASI ≤3, otherwise as nonresponders. The genotypes of 4 single-nucleotide polymorphisms (SNPs) in the ANxA6 gene were verified using the Sequenom platform. Potential predictors associated with the treatment outcome of MTX were assessed by binary logistic regression. Results: We found significant associations for the ANxA6 SNPs of rs11960458, rs960709, and rs13168551 with psoriasis severity. Patients with rs11960458 CC genotype and rs960709 GG genotype showed higher percentages of PASI75 and improvement rates of PASI at 12 weeks. And on 1-year treatment, statistical difference occurred in rs11960458 rather than other SNPs compared between responders and nonresponders that the frequency of CC genotype was higher in responders (p = 0.019). After adjustment for potential confounders, patients with rs11960458 TT/CT genotype (at 12 weeks: OR 0.483, 95% CI 0.245–0.951, p = 0.035; at 1 year: OR 0.483, 95% CI 0.280–0.833, p = 0.009) were significantly more likely to not respond to MTX both on the short-term and long-term treatment, while rs960709 and rs13168551 polymorphisms were only associated with the short-term efficacy of MTX (p = 0.018 and p = 0.036, respectively). Conclusions: The CC ge­notype of ANxA6 (rs11960458) was significantly associated with a better response when compared to those patients with the TT/CT genotype, thus being a potential predictor for the clinical efficacy of MTX.
Management eines neu diagnostizierten metastasierten testikulären Keimzelltumors bei einem COVID-19 positiven Patienten
Authors: Almassi Nima , Mulhall John P , Funt Samuel A. , Sheinfeld Joel
Published: February 2021

Ein 17-jähriger Mann mit anamnestisch bekanntem kongenitalen Solitärhoden auf der linken Seite stellte sich Ende April 2020 mit einer seit mehreren Wochen bestehenden linksseitigen Hodenschwellung und Beschwerden in unserer Klinik vor. Die Frage nach einer ungewollten Gewichtsabnahme oder Empfindlichkeit der Brustwarzen wurde vom Patient verneint; er berichtete jedoch über neu aufgetretene, leichte linksseitige Rückenbeschwerden. Als Auffälligkeiten in der medizinischen Vorgeschichte fanden sich Asthma sowie ein kongenitales Fehlen des rechten Hodens, weswegen bei dem Patienten in der Kindheit eine chirurgische Exploration mit negativem Ergebnis erfolgt war.
Translating Expertise across Work Contexts: U.S. Puppeteers Move from Stage to Screen
Authors: Anteby Michel , Holm Audrey L.
Published: February 2021

Expertise is a key currency in today’s knowledge economy. Yet as experts increasingly move across work contexts, how expertise translates across contexts is less well understood. Here, we examine how a shift in context—which reorders the relative attention experts pay to distinct types of audiences—redefines what it means to be an expert. Our study’s setting is an established expertise in the creative industry: puppet manipulation. Through an examination of U.S. puppeteers’ move from stage to screen (i.e., film and television), we show that, although the two settings call on mostly similar techniques, puppeteers on stage ground their claims to expertise in a dialogue with spectators and view expertise as achieving believability; by contrast, puppeteers on screen invoke the need to deliver on cue when dealing with producers, directors, and co-workers and view expertise as achieving task mastery. When moving between stage and screen, puppeteers therefore prioritize the needs of certain audiences over others’ and gradually reshape their own views of expertise. Our findings embed the nature of expertise in experts’ ordering of types of audiences to attend to and provide insights for explaining how expertise can shift and become co-opted by workplaces.
Post-contrast Acute Kidney Injury Following Emergency Transcatheter Arterial Embolization for Uncontrollable Postpartum Hemorrhage
Authors: Seki Yuko , Miyazaki Masaya , Suto Takayuki , Kameda Takashi , Tsushima Yoshito
Published: February 2021

The aim of this study was to investigate the incidence of post-contrast acute kidney injury (PC-AKI) in patients with uncontrollable postpartum hemorrhage undergoing emergency transcatheter arterial embolization (TAE). Data collected included patient characteristics, serum creatinine (SCr) level before and after TAE, iodine quantity of contrast media, time between computed tomography and TAE, diabetes mellitus, hemorrhage volume, and blood transfusion volume. For the diagnosis of PC-AKI, the criteria of the European Society of Urogenital Radiology Guidelines (version 10.0) were used. A total of 71 TAE procedures were performed over a 5-year period, and 47 patients met the inclusion criteria. Preprocedural renal function and change of SCr were positively correlated ( P < .001), although no patients met the PC-AKI criteria and none showed renal impairment on the follow-up examination (95% upper confidence limit = 6.2%). Total iodine quantity was not correlated with SCr change. Postpartum hemorrhage was finally controlled in all 47 patients, and they were subsequently discharged. In conclusion, emergency TAE for patients with uncontrollable postpartum hemorrhage was a safe and effective procedure, not only in terms of bleeding-related and other outcomes but also with respect to the risk of PC-AKI.
A New Index for the Prediction of 30-Day Mortality in Patients With Pulmonary Embolism: The Pulmonary Embolism Mortality Score (PEMS)
Authors: Surov Alexey , Akritidou Mideia , Bach Andreas Gunther , Bailis Nikolaos , Lerche Marianne , Meyer Hans Jonas , Pech Maciej , Wienke Andreas
Published: February 2021

Our aim was to analyze possibility of combination of basic clinical and radiological signs to predict 30-day mortality after acute pulmonary embolism (PE). We included 486 patients. Age, gender, simplified pulmonary embolism index (sPESI), pH, troponin, N-terminal natriuretic peptide, minimal systolic and diastolic blood pressure, O2 saturation, syncope, need for vasopressors, thrombotic obstruction, vessel diameter, short axis ratio right ventricle/left ventricle, and contrast medium reflux into the inferior vena cava (IVC) were analyzed. A backward algorithm in a logistic regression model was used to identify relevant risk factors. Multiple logistic regression analysis identified that sPESI, pH, minimal diastolic blood pressure, IVC reflux, and need for vasopressors influenced 30-day mortality. A score for mortality prediction was constructed (the Pulmonary Embolism Mortality Score): sPESI >2 points (1 point), pH <7.35 (1 point), minimal diastolic blood pressure <45 mm Hg (1 point), IVC reflux (1 point), and need for vasopressors (2 points). Patients with >3 points showed higher 30-day mortality (sensitivity: 84.9%, specificity: 83.0%, positive predictive value: 51.8%, negative predictive value: 96.2%). The net reclassification improvement compared with the sPESI was 0.94 (95% CI = 0.73-1.15). In conclusion, a new score can predict 30-day mortality in patients with PE and is more sensitive than sPESI.