bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fetal echocardiography and early neonatal balloon valvuloplasty improved overall survival in prenatally detected aortic stenosis over 25 years of tertiary center experience
Authors: Sylwestrzak Oskar , Strzelecka Iwona , Wójtowicz‐Marzec Monika , Krekora Michał , Moszura Tomasz , Słodki Maciej , Respondek‐Liberska Maria 
Published: September 2022

AbstractPurposeThis article aimed to present the factors determining survival and prognosis in fetuses and newborns with critical prenatal aortic stenosis (AS) and to present 26 years of tertiary center experience.MethodsStudy included 87 fetuses with critical AS requiring surgical intervention during neonatal period. All results were expressed as means ± SD, in numbers and percentages. The statistically significant results were those with p < 0.05.ResultsAn increase in the number of cases of AS was observed in our center along with a decrease in gestational age of our patients during the first echocardiographic exam. The survival rate of newborns was considerably higher when born in due time (p < 0.05) with body weight > 2500 g (p < 0.05). Balloon valvuloplasty performed in the first days after birth occurred to be an optimal solution in these cases.ConclusionsFetal echocardiography and special perinatal care with transplacental maternal pharmacotherapy in selected cases and an early neonatal aortic balloon valvuloplasty have shown improvement in survival rate. The most dangerous for the newborn with AS was the first week of postnatal life. It is vital to refer the fetuses with AS to the reference centers which offer the possibility of invasive cardiac intervention on the first day after birth, and it might be an optimal solution.
Use of Elamipretide in patients assigned treatment in the compassionate use program: Case series in pediatric patients with rare orphan diseases
Authors: Koenig Mary Kay , Russo Sam Nick , McBride Kim L. , Bjornsson Hans Tomas , Gunnarsdottir Brynja Bjork , Goldstein Amy , Falk Scott A. 
Published: September 2022

AbstractSeveral mitochondrial diseases are caused by pathogenic variants that impair membrane phospholipid remodeling, with no FDA‐approved therapies. Elamipretide targets the inner mitochondrial membrane where it binds to cardiolipin, resulting in improved membrane stability, cellular respiration, and ATP production. In clinical trials, elamipretide produced clinical and functional improvements in adults and adolescents with mitochondrial disorders, such as primary mitochondrial myopathy and Barth syndrome; however, experience in younger patients is limited and to our knowledge, these are the first case reports on the safety and efficacy of elamipretide treatment in children under 12 years of age. We describe the use of elamipretide in patients with mitochondrial disorders to provide dosing parameters in patients aged <12 years.
Transcriptome‐wide summary data‐based Mendelian randomization analysis reveals 38 novel genes associated with severe COVID‐19
Authors: Krishnamoorthy Suhas , Li Gloria H.‐Y. , Cheung Ching‐Lung 
Published: September 2022

AbstractSevere COVID‐19 has a poor prognosis, while the genetic mechanism underlying severe COVID‐19 remains largely unknown. We aimed to identify genes that are potentially causally associated with severe COVID‐19. We conducted a summary data‐based Mendelian randomization (SMR) analysis using expression quantitative trait loci (eQTL) data from 49 different tissues as the exposure and three COVID‐19‐phenotypes (very severe respiratory confirmed COVID‐19 [severe COVID‐19], hospitalized COVID‐19, and SARS‐CoV‐2 infection) as the outcomes. SMR using multiple SNPs was used as a sensitivity analysis to reduce false positive rate. Multiple testing was corrected using the false discovery rate (FDR) q‐value. We identified 309 significant gene‐trait associations (FDR q value < 0.05) across 46 tissues for severe COVID‐19, which mapped to 64 genes, of which 38 are novel. The top five most associated protein‐coding genes were Interferon Alpha and Beta Receptor Subunit 2 (IFNAR2), 2′‐5′‐Oligoadenylate Synthetase 3 (OAS3), mucin 1 (MUC1), Interleukin 10 Receptor Subunit Beta (IL10RB), and Napsin A Aspartic Peptidase (NAPSA). The potential causal genes were enriched in biological processes related to type I interferons, interferon‐gamma inducible protein 10 production, and chemokine (C‐X‐C motif) ligand 2 production. In addition, we further identified 23 genes and 5 biological processes which are unique to hospitalized COVID‐19, as well as 13 genes that are unique to SARS‐CoV‐2 infection. We identified several genes that are potentially causally associated with severe COVID‐19. These findings improve our limited understanding of the mechanism of COVID‐19 and shed light on the development of therapeutic agents for treating severe COVID‐19.
Global buyer–supplier networks and innovation: The role of technological distance and technological breadth
Authors: Palit Shubhobrata , Hora Manpreet , Ghosh Soumen 
Published: September 2022

AbstractOne of the critical challenges of technology management for a firm is managing technological knowledge. This study focuses on available technological knowledge in a firm's global supplier network and examines factors that accrue innovation benefits from such knowledge for a buyer firm. Using absorptive capacity as a theoretical lens, we specifically examine technological distance, technological breadth, and extent of global sourcing, and how these factors interrelate in influencing a firm's innovation performance. The panel data is drawn from various sources (Bloomberg SPLC, PATSTAT Global, and Compustat). Our sample spans four years from 2011 through 2014 and comprises an unbalanced panel of 878 firm‐year observations derived from buyer–supplier relationship data of 246 unique buyer firms. Embedded in this data are 846 unique supplier firms and 9291 dyads (buyer–supplier pairs). The findings confirm the negative association between technological distance and innovation performance, and the positive association between technological breadth and innovation performance. Contrary to expectations, technological distance plays a negative moderating role in the relationship between technological breadth and innovation performance. The results also show that while the extent of a firm's global sourcing has a positive relationship with its innovation performance, the relationship changes with technological distance.
How information technology automates and augments processes: Insights from Artificial‐Intelligence‐based systems in professional service operations
Authors: Spring Martin , Faulconbridge James , Sarwar Atif 
Published: September 2022

AbstractThis study contributes to the technology management literature on the effects of IT on operations processes by examining the use of systems based on Artificial Intelligence (AI) in professional services. The paper builds on key concepts on AI, information systems, professional work, and professional services operations management. A model is developed to explain how AI‐based systems combine with humans to do work, both automating and augmenting the work of the professional, leading to process improvement and extension of the service offering. The study uses case‐based research in two law firms and two accountancy firms using AI‐based systems. It shows that AI‐based systems are used selectively, mainly on high‐volume, back‐office tasks, across the sequence of stages in the professional service process—diagnosis, inference, and treatment. Automation using AI relieves professionals from repetitive tasks, while AI achieves augmentation by buffering professionals from low‐value activity, making their expertise scalable and providing new analytical insights. System use can improve performance in delivering core professional services and enable service extension into additional, high‐value advisory work. The model and research approach have potential implications for other emerging areas of technology management in OM.
Regulation of skeletal muscle protein synthesis in the preterm pig by intermittent leucine pulses during continuous parenteral feeding
Authors: Rudar Marko , Suryawan Agus , Nguyen Hanh V. , Chacko Shaji K. , Vonderohe Caitlin , Stoll Barbara , Burrin Douglas G. , Fiorotto Marta L. , Davis Teresa A. 
Published: September 2022

AbstractBackgroundExtrauterine growth restriction is a common complication of preterm birth. Leucine (Leu) is an agonist for the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) signaling pathway that regulates translation initiation and protein synthesis in skeletal muscle. Previously, we showed that intermittent intravenous pulses of Leu to neonatal pigs born at term receiving continuous enteral nutrition increases muscle protein synthesis and lean mass accretion. Our objective was to determine the impact of intermittent intravenous pulses of Leu on muscle protein anabolism in preterm neonatal pigs administered continuous parenteral nutrition.MethodsFollowing preterm delivery (on day 105 of 115 gestation), pigs were fitted with umbilical artery and jugular vein catheters and provided continuous parenteral nutrition. Four days after birth, pigs were assigned to receive intermittent Leu (1600 µmol kg−1 h−1; n = 8) or alanine (1600 µmol kg−1 h−1; n = 8) parenteral pulses every 4 h for 28 h. Anabolic signaling and fractional protein synthesis were determined in skeletal muscle.ResultsLeu concentration in the longissimus dorsi and gastrocnemius muscles increased in the leucine (LEU) group compared with the alanine (ALA) group (P < 0.0001). Despite the Leu‐induced disruption of the Sestrin2·GATOR2 complex, which inhibits mTORC1 activation, in these muscles (P < 0.01), the abundance of mTOR·RagA and mTOR·RagC was not different. Accordingly, mTORC1‐dependent activation of 4EBP1, S6K1, eIF4E·eIF4G, and protein synthesis were not different in any muscle between the LEU and ALA groups.ConclusionIntermittent pulses of Leu do not enhance muscle protein anabolism in preterm pigs supplied continuous parenteral nutrition.
Factors associated with pathologic complete response following neoadjuvant chemoradiation and esophagectomy for carcinoma of esophagus and gastroesophageal junction
Authors: Nusrath Syed , Thammineedi Subramanyeshwar R. , Raju Kalidindi Venkata Vijaya Narsimha , Patnaik Sujith C. , Saksena Ajesh R. , Karthik Jaya , Basude Madhunarayana , Kumar J Pavan , Shukla Srijan , Rao Vishal B. , Kumar C Kishore , Gujjuru Swathi , Tewani Rohan , Rushdie Tasneem , Sudhir Rashmi , Smith Lynette M. , Are Chandrakanth 
Published: September 2022

AbstractBackground and ObjectivesThe aim of this study was to analyze factors associated with pathologic complete response (pCR) following neoadjuvant chemoradiation (NCRT) and esophagectomy for carcinoma of the esophagus (EC) and gastroesophageal junction (GEJ).MethodsPatients with EC and GEJ tumors who received NCRT and underwent esophagectomy between January 2010 to March 2021 were included. Univariate and multivariate analyses were performed to evaluate the factors associated with pCR by comparing the patients who achieved pCR (pCR group) with those who did not achieve pCR (non‐pCR group).ResultsA total of 321 patients were included in the study, with squamous cell carcinoma (SCC) accounting for the majority of cases (76%). One hundred and sixty (49.8%) patients had pCR. SCC histology and pretreatment radiographic node‐negative status (cN0) were associated with pCR. Patients in the pCR group had significantly better overall and disease‐free survival compared with patients in the non‐pCR group.ConclusionsSCC histology and pretreatment radiographic node‐negative status were associated with pCR. For patients with tumors of EC and GEJ who received NCRT and underwent esophagectomy, pCR was associated with improved prognosis compared with those not achieving pCR.
Grazer‐induced aggregation in diatoms
Authors: Grønning Josephine , Kiørboe Thomas 
Published: September 2022

AbstractSinking is part of diatom life history. Typically, by the end of a bloom, diatoms form aggregates that sink rapidly to the bottom. This opportunistic lifestyle can be considered an adaptation to reduce predation losses, because predation pressure in the sediment is less than that in the water column. In this study, we demonstrate that two out of six examined diatoms become sticky and coagulate into aggregates when exposed to chemical copepod cues. Cell stickiness increases proportionally to the concentration of copepod cues and duration of exposure until saturation. Surprisingly, nutrient limitation (Si and N) did not increase stickiness. Furthermore, we demonstrate a chain length reduction of Skeletonema marinoi, when exposed to copepod cues. We argue that the increase in stickiness is adaptive when grazing mortality exceeds growth rate. This ensures that the maximum number of cells survive in the sediment, ready to utilize the next window of growth opportunity.
Combination 1550 nm non‐ablative fractional resurfacing and laser hair removal for treatment of Becker's nevi in skin types III–VI
Authors: Kubicki Shelby L. , Guo Emily L. , Sodha Pooja , Richmond Heather , Friedman Paul M. 
Published: September 2022

AbstractObjectivesBecker's nevus is a cosmetically bothersome benign hamartoma typically associated with basal layer hyperpigmentation and hypertrichosis. We herein present the largest case series characterizing treatment parameters and clinical outcomes of combined 1550 nm non‐ablative fractional resurfacing and laser hair removal (long‐pulsed neodymium‐doped yttrium aluminum garnet or alexandrite) in the treatment of Becker's nevus. This is also the largest case series of laser treatment of Becker's nevus in Fitzpatrick skin types V and VI.MethodsWe performed a retrospective review of patients treated between 2016 and 2021. Clinical photographs were graded by three independent physicians using a 5‐point visual analog scale.ResultsTwelve patients (mean age: 24.8 years, Fitzpatrick skin types III–VI) were treated for Becker's nevus on the face (4) or the trunk and/or extremities (8). Four patients were Fitzpatrick skin types V or VI. On average, patients received 5.3 treatments in 1–4‐month intervals. Ten of the 12 patients had concomitant laser hair removal preceding same‐day non‐ablative fractional resurfacing (n = 7 with long‐pulsed 1064 nm neodymium‐doped yttrium aluminum garnet and n = 3 with long‐pulsed 755 nm alexandrite). The number of treatments with each modality was determined by patient satisfaction with improvement in hyperpigmentation and hypertrichosis. At follow‐up, which ranged from 6 to 40 weeks (mean 10.5 weeks), patients were given a mean improvement score of 51%–75%.No long‐term adverse events were encountered in either group. Limitations include a small sample size and a lack of long‐term follow‐up.ConclusionCombination 1550 nm non‐ablative fractional resurfacing and laser hair removal is safe and efficacious in the cosmetic reduction of hyperpigmentation and hypertrichosis associated with Becker's nevus, including those with Fitzpatrick skin types V and VI.
Outcomes of patients who underwent treatment for anti‐HLA donor‐specific antibodies before receiving a haploidentical hematopoietic cell transplant
Authors: Lipsitt Amanda , Arnold Paula , Chi Liying , Carruthers Katharine , Folk Sophia , Fossey Sallyanne , Keerthi Dinesh , Mamcarz Ewelina , Srinivasan Ashok , Sharma Akshay 
Published: September 2022

AbstractPediatric and adolescent and young adult (AYA) patients who receive many blood product transfusions, such as individuals with sickle cell disease (SCD), severe aplastic anemia (SAA) or indolent hematologic malignancies, are at high risk for developing donor‐specific antibodies (DSA). DSAs with mean fluorescence intensity (MFI) greater than 5000 have been associated with significant graft failure, but lower MFI values between 2000 and 5000 may result in poor graft function after hematopoietic cell transplant (HCT). Desensitization strategies have been developed to reduce the DSA burden in HCT recipients before graft infusion, but the experience with these strategies in the pediatric and AYA populations is not well described in the literature. Here, we describe our experience with successful desensitization by using a combination of treatment strategies in five pediatric and AYA patients, including a novel use of daratumumab in a young adult patient who had refractory DSAs and had suffered serious side effects from conventional desensitization strategies. The presence of elevated DSAs in pediatric and AYA recipients of a human leukocyte antigen (HLA)‐mismatched haploidentical HCT can be overcome by a multipronged treatment strategy.
Record linkage of claims and cancer registries data—Evaluation of a deterministic linkage approach based on indirect personal identifiers
Authors: Kollhorst Bianca , Reinders Tammo , Grill Susann , Eberle Andrea , Intemann Timm , Kieschke Joachim , Meyer Martin , Nennecke Alice , Rathmann Wolfgang , Pigeot Iris 
Published: September 2022

AbstractPurposeIn Germany, record linkage of claims and cancer registry data is cost‐ and time‐consuming, since up until recently no unique personal identifier was available in both data sources. The aim of this study was to evaluate the feasibility and performance of a deterministic linkage procedure based on indirect personal identifiers included in the data sources.MethodsWe identified users of glucose‐lowering drugs with residence in four federal states in Northern and Southern Germany (Bavaria, Bremen, Hamburg, Lower Saxony) in the German Pharmacoepidemiological Research Database (GePaRD) and assessed colorectal and thyroid cancer cases. Cancer registries of the federal states selected all colorectal and thyroid cancer cases between 2004 and 2015. A deterministic linkage approach was performed based on indirect personal identifiers such as year of birth, sex, area of residence, type of cancer and an absolute difference between the dates of cancer diagnosis in both data sources of at most 90 days. Results were compared to a probabilistic linkage using “direct” personal identifiers (gold standard).ResultsThe deterministic linkage procedure yielded a sensitivity of 71.8% for colorectal cancer and 66.6% for thyroid cancer. For thyroid cancer, the sensitivity improved when using only inpatient diagnosis to define cancer in GePaRD (71.4%). Specificity was always above 99%. Using the probabilistic linkage to define cancer cases, the risk for colorectal cancer was estimated 10 percentage points lower than when using the deterministic approach.ConclusionsSensitivity of the deterministic linkage approach appears to be too low to be considered as reasonable alternative to the probabilistic linkage procedure.
Estimating conformational heterogeneity of tryptophan synthase with a template‐based Alphafold2 approach
Authors: Casadevall Guillem , Duran Cristina , Estévez‐Gay Miquel , Osuna Sílvia 
Published: September 2022

AbstractThe three‐dimensional structure of the enzymes provides very relevant information on the arrangement of the catalytic machinery and structural elements gating the active site pocket. The recent success of the neural network Alphafold2 in predicting the folded structure of proteins from the primary sequence with high levels of accuracy has revolutionized the protein design field. However, the application of Alphafold2 for understanding and engineering function directly from the obtained single static picture is not straightforward. Indeed, understanding enzymatic function requires the exploration of the ensemble of thermally accessible conformations that enzymes adopt in solution. In the present study, we evaluate the potential of Alphafold2 in assessing the effect of the mutations on the conformational landscape of the beta subunit of tryptophan synthase (TrpB). Specifically, we develop a template‐based Alphafold2 approach for estimating the conformational heterogeneity of several TrpB enzymes, which is needed for enhanced stand‐alone activity. Our results show the potential of Alphafold2, especially if combined with molecular dynamics simulations, for elucidating the changes induced by mutation in the conformational landscapes at a rather reduced computational cost, thus revealing its plausible application in computational enzyme design.
Stabilizing proteins, simplified: A Rosetta‐based webtool for predicting favorable mutations
Authors: Thieker David F. , Maguire Jack B. , Kudlacek Stephan T. , Leaver‐Fay Andrew , Lyskov Sergey , Kuhlman Brian 
Published: September 2022

AbstractMany proteins have low thermodynamic stability, which can lead to low expression yields and limit functionality in research, industrial and clinical settings. This article introduces two, web‐based tools that use the high‐resolution structure of a protein along with the Rosetta molecular modeling program to predict stabilizing mutations. The protocols were recently applied to three genetically and structurally distinct proteins and successfully predicted mutations that improved thermal stability and/or protein yield. In all three cases, combining the stabilizing mutations raised the protein unfolding temperatures by more than 20°C. The first protocol evaluates point mutations and can generate a site saturation mutagenesis heatmap. The second identifies mutation clusters around user‐defined positions. Both applications only require a protein structure and are particularly valuable when a deep multiple sequence alignment is not available. These tools were created to simplify protein engineering and enable research that would otherwise be infeasible due to poor expression and stability of the native molecule.
Structure of lactate oxidase from Enterococcus hirae revealed new aspects of active site loop function: Product‐inhibition mechanism and oxygen gatekeeper
Authors: Hiraka Kentaro , Yoshida Hiromi , Tsugawa Wakako , Asano Ryutaro , La Belle Jeffrey T. , Ikebukuro Kazunori , Sode Koji 
Published: September 2022

Abstractl‐Lactate oxidase (LOx) is a flavin mononucleotide (FMN)‐dependent triose phosphate isomerase (TIM) barrel fold enzyme that catalyzes the oxidation of l‐lactate using oxygen as a primary electron acceptor. Although reductive half‐reaction mechanism of LOx has been studied by structure‐based kinetic studies, oxidative half‐reaction and substrate/product‐inhibition mechanisms were yet to be elucidated. In this study, the structure and enzymatic properties of wild‐type and mutant LOxs from Enterococcus hirae (EhLOx) were investigated. EhLOx structure showed the common TIM‐barrel fold with flexible loop region. Noteworthy observations were that the EhLOx crystal structures prepared by co‐crystallization with product, pyruvate, revealed the complex structures with “d‐lactate form ligand,” which was covalently bonded with a Tyr211 side chain. This observation provided direct evidence to suggest the product‐inhibition mode of EhLOx. Moreover, this structure also revealed a flip motion of Met207 side chain, which is located on the flexible loop region as well as Tyr211. Through a saturation mutagenesis study of Met207, one of the mutants Met207Leu showed the drastically decreased oxidase activity but maintained dye‐mediated dehydrogenase activity. The structure analysis of EhLOx Met207Leu revealed the absence of flipping in the vicinity of FMN, unlike the wild‐type Met207 side chain. Together with the simulation of the oxygen‐accessible channel prediction, Met207 may play as an oxygen gatekeeper residue, which contributes oxygen uptake from external enzyme to FMN. Three clades of LOxs are proposed based on the difference of the Met207 position and they have different oxygen migration pathway from external enzyme to active center FMN.