bluuebunny/crossref_metadata_2025 huggingface dataset:
Early identification and treatment of women's cardiovascular risk factors prevents cardiovascular disease, saves lives, and protects future generations: Policy recommendations and take action plan utilizing policy levers
Authors: Ivey Susan L. , Hanley Hattie Rees , Taylor Catrina , Stock Eveline , Vora Nirali , Woo Jenny , Johnson Sara , Bairey Merz C. Noel ,   Right Care Women's Cardiovascular Writing Group
Published: September 2022

Cardiovascular diseases (CVD) including heart attacks, strokes, heart failure, and uncontrolled hypertension are leading causes of death among women of all ages. Despite efforts to increase awareness about CVD among women, over the past decade there has been stagnation in the reduction of CVD in women, and CVD among younger women and women of color has in fact increased. We recommend taking action using policy levers to address CVD in women including: (1) Promoting periodic screening for risk factors including blood pressure, lipids/cholesterol, diabetes for all women starting at 18–21 years, with calculated atherosclerotic CVD (ASCVD) risk score use among women 40 years or older. (2) Considering coronary artery calcium (CAC) screening for those with intermediate risk per current guidelines. (3) Enhancing Obstetrics and Gynecology and primary care physician education on reproductive age CVD risk markers, and that follow‐up is needed, including extended postpartum follow‐up. (4) Offering Health Coaching/motivational Interviewing to support behavior change. (5) Funding demonstration projects using different care models. (6) Creating a Stop High Blood Pressure consult line (for providers and patients) and providing other support resources with actions consumers can take, modeled after the California tobacco quit line. And (7) Requiring inclusion of adverse pregnancy outcomes in all Electronic Health Records, with reminder systems to follow‐up on hypertension post‐partum.
Total Synthesis and Antibacterial Investigations of 1‐Hydroxyboivinianin A
Authors: Wilt Ingrid K. , Demeritte Adrian R. , Wang Weiwei , Wuest William M.
Published: September 2022

Synthetic investigations of natural products has been instrumental in the development of novel antibacterial small molecules. 1‐hydroxyboivinianin A, a lactone containing phenolic bisabolane isolated from marine sediment, has reported antibacterial activity against the aquatic pathogen Vibrio harveyi. The total synthesis of 1‐hydroxyboivinianin A and its enantiomer was completed in a six‐step sequence in 42 % overall yield. The synthesis leveraged a key diastereoselective nucleophilic addition with chiral imidazolidinone to establish the benzylic tertiary alcohol and intramolecular Horner‐Wadsworth Emmons to furnish the lactone. Both enantiomers were found to have negligible antibacterial activity against a panel of gram‐positive and negative bacteria and minimal antifungal activity against phytopathogens. Investigations of a possible in vitro lactone hydrolysis to produce an inactive linear acid led to the discovery of a spontaneous cyclization, suggesting the lactone is resistant to hydrolysis and the lactone is not degrading to produce an inactive species.
A Tug of War between the Self‐ and Cross‐associating Hydrogen Bonds in Neutral Ammonia‐Water Clusters: Energetic Insights by Molecular Tailoring Approach
Authors: Patkar Deepak , Bharati Ahirwar Mini , Deshmukh Milind M.
Published: September 2022

In the present work, the energies of various types of individual HBs observed in neutral (NH3)m(H2O)n, (m+n=2 to 7) clusters were estimated using the molecular tailoring approach (MTA)‐based method. The calculated individual HB energies suggest that the O−H…N HBs are the strongest (1.21 to 12.49 kcal mol−1). The next ones are the O−H…O (3.97 to 9.30 kcal mol−1) HBs. The strengths of N−H…N (1.09 to 5.29 kcal mol−1) and N−H…O (2.85 to 5.56 kcal mol−1) HBs are the weakest. The HB energies in dimers also follow this rank ordering. However, the HB energies in dimers are much smaller than those obtained by the MTA‐based method due to the loss in cooperativity contribution in the dimers. Thus, the calculated cooperativity contributions, for different types of HBs, fall in the range 0.64 to 5.73 kcal mol−1. We wish to emphasize based on the energetic rank ordering obtained by the MTA‐based method that the O−H of water is a better HB donor than the N−H of ammonia. The reasons for the observed energetic rank ordering are two folds: (i) intrinsically stronger O−H…N HBs than the O−H…O ones as revealed by dimer energies and (ii) the higher cooperativity contribution in the former than the later ones. Indeed, the MTA‐based method is useful in providing the missing energetic rank ordering of various type of HBs in neutral (NH3)m(H2O)n clusters, in the literature.
On the realization of VANET using named data networking: On improvement of VANET using NDN‐based routing, caching, and security
Authors: da Silva Elídio Tomás , Costa António Luís Duarte , de Macedo Joaquim Melo Henriques
Published: September 2022

Named data networking (NDN) presents a huge opportunity to tackle some of the unsolved issues of IP‐based vehicular ad hoc networks (VANET). The core characteristics of NDN such as the name‐based routing, in‐network caching, and built‐in data security provide better management of VANET proprieties (e.g., the high mobility, link intermittency, and dynamic topology). This study aims at providing a clear view of the state‐of‐the‐art on the developments in place, in order to leverage the characteristics of NDN in VANET. We resort to a systematic literature review (SLR) to perform a reproducible study, gathering the proposed solutions and summarizing the main open challenges on implementing NDN‐based VANET. There exist several related studies, but they are more focused on other topics such as forwarding. This work specifically restricts the focus on VANET improvements by NDN‐based routing (not forwarding), caching, and security. The surveyed solution herein presented is performed between 2010 and 2021. The results show that proposals on the selected topics for NDN‐based VANET are recent (mainly from 2016 to 2021). Among them, caching is the most investigated topic. Finally, the main findings and the possible roadmaps for further development are highlighted.
No seasonal curtailment of the Eurasian Skylark's (Alauda arvensis) breeding season in German heterogeneous farmland
Authors: Püttmanns Manuel , Lehmann Franziska , Willert Fabian , Heinz Jasmin , Kieburg Antje , Filla Tim , Balkenhol Niko , Waltert Matthias , Gottschalk Eckhard
Published: September 2022

The lack of suitable nesting sites is one key driver behind the farmland bird crisis in Europe. Winter cereals become impenetrable for ground‐breeding birds like the Eurasian Skylark (Alauda arvensis), curtailing breeding time. Stable Skylark populations depend on multiple breeding attempts per year; thus, the widespread cultivation of winter cereals has strongly contributed to their tremendous decline. Crop diversification is thought to be a potential measure to counteract this development. Therefore, we explored how individual Skylarks respond to the decreasing suitability of winter cereals as nesting habitats in heterogeneous but otherwise conventionally managed farmland. Our study focused on: (i) the degree to which Skylarks prematurely cease nesting activity, switch nesting habitats, or breed on linear structures like tramlines. Additionally, we analyzed: (ii) if nest success decreases throughout the breeding season and (iii) how often Skylarks make a successful breeding attempt per year. We radio‐tagged 28 adults in a German population during April 2018 and 2019, tracked half of them for more than 3 months, and measured their breeding success. Additionally, we monitored nests of untagged pairs, resulting in 96 nests found. None, except one tagged individual, stopped breeding activity before July 1st. Home ranges were mainly stable, but Skylarks switched nesting habitats away from winter cereals to crops like sugar beet or set‐aside. High‐risk nesting sites like corn and linear structures played a minor role in breeding. Overall, Mayfield logistic regressions revealed no seasonal decrease in nest success, and tagged Skylarks had sufficient time to make 1.5–1.8 breeding attempts, of which 0.8 were successful. We suggest that heterogeneous farmland in our study area, which enabled diversely composed home ranges, prevented a curtailment of the breeding season. Thus, our study reinforces the need for crop diversification which gives Skylarks a chance to survive in modern farmland.
Contemporary outcome of subsequent pregnancies in patients with previous peripartum cardiomyopathy
Authors: Goland Sorel , George Jacob , Elkayam Uri , Shimoni Sara , Fugenfirov Irena , Vaisbuch Edi , Arad Michael , Freimark Dov , Simchen Michal , Kuperstein Rafael
Published: September 2022

Aims

To describe the effect of subsequent pregnancies (SSP) on left ventricular (LV) function and outcomes in patients with peripartum cardiomyopathy (PPCM).

Methods

Among146 women with PPCM who were prospectively followed at two medical centres in Israel (2007–2019), 75 SSPs (in 50 women) were identified: 8 miscarriages, 8 terminations, and 59 life birth.

Results

Forty‐five patients with 59 full‐term SSPs [mean age was 32.9 ± 4.1 years, LV ejection fraction (LVEF) 57.7 ± 5.1%] were analysed.

Data on LVEF at 1‐month post‐delivery were available in 46 and at 6 months in 36 SSPs. There was a small decrease in the mean LVEF, mostly at third trimester (57.2 ± 5.6 vs. 54.4. ± 7.3, P < 0.001); and at 1‐mont (57.9 ± 5.7% vs. 55.4 ± 6.1%, P = 0.001) and at 6‐month post‐delivery (57.4 ± 6.1 vs. 55.3 ± 7.9%, P = 0.03).

In patients with pre‐SSP LV LVEF ≥55%, a mild reduction in the mean group LVEF was seen at 1‐month post‐delivery (P = 0.009). One patient with pre‐SSP LVEF ≥55% developed severe relapse. In patients with pre‐SSP LVEF <55%, a mild reduction in LVEF was obtained mostly at third trimester (51.1 ± 5.6 vs 47.0 ± 7.4%, P < 0.001), which persisted at 6 months (P = 0.03). A relapse was observed in three (25%) women with LVEF <55%. There was no maternal mortality, 32 patients delivered by caesarean section, and there were no foetal complications.

Conclusions

Our study indicates a favourable outcome and low likelihood of maternal mortality associated with SSP in women with a history of PPCM and recovered LV systolic function. SSP was associated with a slight reduction in LVEF mostly during the third trimester, which persisted up to 6 months after delivery.
An echo score raises the suspicion of cardiac amyloidosis in Chinese with heart failure with preserved ejection fraction
Authors: Yang Hong , Li Rui , Ma Fei , Wei Ye , Liu Yujian , Sun Yang , He Xingwei , Zeng Hesong , Yan Jiangtao , Wang Dao Wen , Wang Hong
Published: September 2022

Aims

Transthyretin cardiac amyloidosis (ATTR‐CA) has been realized as an important cause of heart failure with preserved ejection fraction (HFpEF). We aim to provide insights into its prevalence in Chinese HFpEF patients, which is not known to date, using increased wall thickness (IWT) score by echocardiography.

Methods

Consecutive patients with HFpEF (EF ≥ 40%) and IWT (≥12 mm) were prospectively screened. Echocardiography was performed, and the IWT score incorporated relative wall thickness, E/e′ ratio, longitudinal strains, and tricuspid annular plane systolic excursion, and septal apical‐to‐base ratio was calculated. ATTR‐CA was defined as score ≥8 in the absence of serum and urine free light chain.

Results

Six hundred twenty‐four HFpEF patients from January 2019 to December 2021 were enrolled, of which 65.2% were males and the median (interquartile range [IQR]) age was 66 (IQR 57, 73) years. Thirty‐three patients (5.3%, 95% CI 3.5–7.0%) were with score ≥8, and 33.3% were females. They were younger (58 vs. 69 years, P < 0.001), had higher NT‐proBNP (6525.0 vs. 1741.5 pg/mL, P < 0.001) and troponin I (105.2 vs. 27.7 pg/mL, P = 0.001) level, and lower LVEF (47% vs. 57%, P < 0.001) compared with the patients with score <5. In the internal cohort (82 patients) who had undergone scintigraphy, the IWT score ≥8 was shown to have a sensitivity of 85.7% (95% CI 56.2–97.5%) and a specificity of 92.6% (95% CI 83.0–97.3%) for diagnosing CA, and the IWT score <5 had great accuracy in excluding CA with the negative predictive value of 100%, supporting the clinical usefulness of the IWT score to guide further dedicated testing for ATTR‐CA.

Conclusions

The IWT score by echocardiography was an excellent tool for screening ATTR‐CA in HFpEF. In Chinese HFpEF patients associated with a hypertrophic phenotype, the proportion of highly suspected ATTR‐CA as detected by IWT score ≥8 was 5.3%, lower than the reported prevalence of ATTR‐CA in non‐Asian patients with the disease.
Preparation and characterization of an intelligent film based on fish gelatin and Coleus scutellarioides anthocyanin to monitor the freshness of rainbow trout fish fillet
Authors: Hematian Fahimeh , Baghaei Homa , Mohammadi Nafchi Abdorreza , Bolandi Marzieh
Published: September 2022

In this study, a pH‐sensitive indicator based on fish gelatin and Coleus scutellarioides anthocyanin extract (CSAE) was prepared and characterized. Films were prepared using the solvent casting method and different levels of CSAE, including 10 ml (CSG1), 20 ml (CSG2), and 30 ml (CSG3), and 0 ml (CSG0) as a control sample. The mechanical, optical, and pH sensing of active films and the release of anthocyanins from the films were investigated. The relationship between the total volatile basic nitrogen (TVB‐N) of fish fillets and a* color index of films was studied. By incorporation of CSAE, the flexibility of films increased, while the tensile strength and UV–Vis light transmittance through the films decreased (p < .05). The films containing the CSAE had a darker, yellowish, and reddish color than the control film. There was a significant relationship between the pH variation and the film color. The films had a purple color at acidic pH, and their color changed to green at an alkaline pH, indicating the sensitivity of the produced films to pH changes. There was a significant relationship between the TVB‐N value of fish fillets and the a* index of the film during the 16 h storage time. The results showed that by increasing TVB‐N values of the fillets, the a* color index decreased, and the films' color changed from purple to colorless. In summary, the active films prepared with fish gelatin and CSAE could be used as pH‐sensitive intelligent packaging to display the freshness of fishery products.
Pten associates with important gene regulatory network to fine‐tune Müller glia‐mediated zebrafish retina regeneration
Authors: Gupta Shivangi , Sharma Poonam , Chaudhary Mansi , Premraj Sharanya , Kaur Simran , Vijayan Vijithkumar , Arun Manas Geeta , Prasad Nagaraj Guru , Ramachandran Rajesh
Published: September 2022

Unlike mammals, zebrafish possess a remarkable ability to regenerate damaged retina after an acute injury. Retina regeneration in zebrafish involves the induction of Müller glia‐derived progenitor cells (MGPCs) exhibiting stem cell‐like characteristics, which are capable of restoring all retinal cell‐types. The induction of MGPC through Müller glia‐reprograming involves several cellular, genetic and biochemical events soon after a retinal injury. Despite the knowledge on the importance of Phosphatase and tensin homolog (Pten), which is a dual‐specificity phosphatase and tumor suppressor in the maintaining of cellular homeostasis, its importance during retina regeneration remains unknown. Here, we explored the importance of Pten during zebrafish retina regeneration. The Pten gets downregulated upon retinal injury and is absent from the MGPCs, which is essential to trigger Akt‐mediated cellular proliferation essential for retina regeneration. We found that the downregulation of Pten in the post‐injury retina accelerates MGPCs formation, while its overexpression restricts the regenerative response. We observed that Pten regulates the proliferation of MGPCs not only through Akt pathway but also by Mmp9/Notch signaling. Mmp9‐activity is essential to induce the proliferation of MGPCs in the absence of Pten. Lastly, we show that expression of Pten is fine‐tuned through Mycb/histone deacetylase1 and Tgf‐β signaling. The present study emphasizes on the stringent regulation of Pten and its crucial involvement during the zebrafish retina regeneration.
Effect of old age on the subpopulations of enteric glial cells in human descending colon
Authors: Baidoo Nicholas , Sanger Gareth J. , Belai Abi
Published: September 2022

Old age is associated with a higher incidence of lower bowel conditions such as constipation. Recent evidence suggest that colonic motility may be influenced by enteric glial cells (EGCs). Little is known about the effect of aging on the subpopulation of EGCs in the human colon. We assessed and compared the pattern of distribution of EGCs in adult and elderly human colon. Human descending colon were obtained from 23 cancer patients comprising of adults (23–63 years; 6 male, 7 female) and elderly (66–81 year; 6 male, 4 female). Specimens were serially‐sectioned and immunolabeled with anti‐Sox‐10, anti‐S100 and anti‐GFAP for morphometric analysis. Standardized procedures were utilized to ensure unbiased counting and densitometric evaluation of EGCs. The number of Sox‐10 immunoreactive (IR) EGCs were unaltered with age in both the myenteric plexus (MP) (respectively, in adult and elderly patients, 1939 ± 82 and 1760 ± 44/mm length; p > .05) and submucosal plexus; there were no apparent differences between adult males and females. The density of S100‐IR EGCs declined among the elderly in the circular muscle and within the MP per ganglionic area. In the adult colon, there were more S100‐IR EGCs distributed in the circular muscle per unit area than the Taenia coli. There was little or no GFAP‐IR EGCs in both adult and elderly colon. We concluded that aging of the human descending colon does not result in a loss of Sox‐10‐IR EGCs in the MP and SMP but reduces S100‐IR EGCs density within the musculature. This alteration in myenteric EGCs density with age may contribute to colonic dysfunction.
Spreading the disease: Protest in times of pandemics
Authors: Lange Martin , Monscheuer Ole
Published: September 2022

This study analyzes the impact of large anti‐lockdown protests on the spread of SARS‐CoV‐2 in Germany. Since protesters at such large gatherings are very mobile and largely neglect SARS‐CoV‐2 containment strategies, they may contribute to the regional transmission of the coronavirus. Employing novel data on bus connections of travel companies specialized in driving protesters to these gatherings, and exploiting the timing of two large‐scale demonstrations in November 2020, we estimate the causal impact of these protests on the spread of SARS‐CoV‐2 using an event study framework. Our findings imply sizable increases in infection rates in protesters' origin regions after these demonstrations. A month after the protests, treated areas face a relative increase in infection rates up to 35% compared to non‐treated areas. Our results shed light on public health consequences of behavior that ignores potential externalities for the society during a pandemic.
Occult metastasis to the superficial level VI lymph nodes in papillary thyroid carcinoma
Authors: Lee Ha Na , Song Chang Myeon , Ji Yong Bae , Myung Jae Kyung , Lee Young‐Jun , Tae Kyung
Published: September 2022

Background

This study aimed to evaluate the incidence and risk factors of occult metastasis to superficial level VI, defined as the space anterior to the strap muscles, including the lymph nodes between the sternocleidomastoid and sternohyoid muscles and suprasternal space lymph nodes.

Methods

We studied 129 patients with papillary thyroid carcinoma who underwent thyroidectomy and neck dissection, including superficial level VI dissection.

Results

Of the 129 patients, 62 (48%) had lymph nodes in the harvested specimens of superficial level VI, and the mean number of lymph nodes retrieved was 1.9 ± 1.2. Occult metastasis to superficial level VI occurred in four patients (3.1%). No significant risk factors of superficial level VI occult metastasis were noted in multivariate analysis.

Conclusions

Occult metastasis to superficial level VI was rare in patients with papillary thyroid carcinoma. Therefore, prophylactic dissection of superficial level VI may not be necessary for primary papillary thyroid carcinoma.
An exploratory investigation of the reliability and validity of the Independent‐Interdependent Problem‐Solving Style Scale
Authors: Sanatkar Samineh , Rubin Mark
Published: September 2022

The Independent‐Interdependent Problem‐Solving Scale is based on Cross et al.'s conceptualisation of relational‐interdependent self‐construal. The IIPSS provides a relatively context‐free measure of people's tendencies to solve problems independently or with the help of others. Because previous investigations have not provided extensive evidence for the reliability and validity of the IIPSS, the current research aimed to test the psychometric properties of this novel measure. Investigations of four student samples (combined N = 1157) and one sample comprised of academic researchers (N = 198) generally supported the reliability and validity of the IIPSS. Exploratory factor analysis of IIPSS items yielded a single factor structure. However, confirmatory factor analyses did not demonstrate good model fit for the one factor solution and instead yielded good model fit for two underlying factors. The IIPSS showed adequate test–retest reliability and predicted positive associations with social personality traits. It also showed no significant associations with measures of demand characteristics and social desirability. Future research needs to be undertaken to further assess the factor structure and address shortcomings of the present research such as utilising objective data in addition to self‐reports to assess the scale's validity.
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

Purpose

This 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.

Methods

Study 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.

Results

An 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.

Conclusions

Fetal 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

Several 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

Severe 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

One 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

This 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

Background

Extrauterine 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.

Methods

Following 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.

Results

Leu 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.

Conclusion

Intermittent 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

Background and Objectives

The 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).

Methods

Patients 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).

Results

A 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.

Conclusions

SCC 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

Sinking 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

Objectives

Becker'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.

Methods

We 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.

Results

Twelve 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.

Conclusion

Combination 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

Pediatric 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

Purpose

In 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.

Methods

We 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).

Results

The 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.

Conclusions

Sensitivity 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

The 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

Many 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

l‐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.
Cold spots are universal in protein–protein interactions
Authors: Gurusinghe Sagara N.S. , Oppenheimer Ben , Shifman Julia M.
Published: September 2022

Proteins interact with each other through binding interfaces that differ greatly in size and physico‐chemical properties. Within the binding interface, a few residues called hot spots contribute the majority of the binding free energy and are hence irreplaceable. In contrast, cold spots are occupied by suboptimal amino acids, providing possibility for affinity enhancement through mutations. In this study, we identify cold spots due to cavities and unfavorable charge interactions in multiple protein–protein interactions (PPIs). For our cold spot analysis, we first use a small affinity database of PPIs with known structures and affinities and then expand our search to nearly 4000 homo‐ and heterodimers in the Protein Data Bank (PDB). We observe that cold spots due to cavities are present in nearly all PPIs unrelated to their binding affinity, while unfavorable charge interactions are relatively rare. We also find that most cold spots are located in the periphery of the binding interface, with high‐affinity complexes showing fewer centrally located colds spots than low‐affinity complexes. A larger number of cold spots is also found in non‐cognate interactions compared to their cognate counterparts. Furthermore, our analysis reveals that cold spots are more frequent in homo‐dimeric complexes compared to hetero‐complexes, likely due to symmetry constraints imposed on sequences of homodimers. Finally, we find that glycines, glutamates, and arginines are the most frequent amino acids appearing at cold spot positions. Our analysis emphasizes the importance of cold spot positions to protein evolution and facilitates protein engineering studies directed at enhancing binding affinity and specificity in a wide range of applications.