bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynemicin A Derivatives as Potential Cancer Chemotherapeutics by Mutasynthesis
Authors: Pal Paramita , Alley Jamie R. , Cohen Douglas R. , Townsend Craig A. 
Published: October 2023

AbstractThe enediyne antitumor antibiotics have remarkable structures and exhibit potent DNA cleavage properties that have inspired continued interest as cancer therapeutics. Their complex structures and high reactivity, however, pose formidable challenges to their production and development in the clinic. We report here proof‐of‐concept studies using a mutasynthesis strategy to combine chemical synthesis of select modifications to a key iodoanthracene‐γ‐thiolactone intermediate in the biosynthesis of dynemicin A and all other known anthraquinone‐fused enediynes (AFEs). By chemical complementation of a mutant bacterial producer that is incapable of synthesizing this essential building block, we show that derivatives of dynemicin can be prepared substituted in the A‐ring of the anthraquinone motif. In the absence of competition from native production of this intermediate, the most efficient utilization of these externally‐supplied structural analogues for precursor‐directed biosynthesis becomes possible. To achieve this goal, we describe the required Δorf15 blocked mutant and a general synthetic route to a library of iodoanthracene structural variants. Their successful incorporation opens the door to enhancing DNA binding and tuning the bioreductive activation of the modified enediynes for DNA cleavage.
Readiness for Weaning Scale: Development and psychometric measurement study
Authors: Türkmen Hülya , Ekşioğlu Aysun , Tuna Oran Nazan , Erdoğan Ayfer 
Published: October 2023

AbstractThis study was carried out to develop a measurement tool to determine the readiness of mothers and babies for weaning. At the first stage of the study, a draft of the Readiness for Weaning Scale (RWS) was created. In the second stage, this draft was presented to the opinions of experts (CVI:0.85), and in the third stage, the validity and reliability of RWS were tested by collecting data from the participants (n = 265). Factor analysis was performed to determine the construct validity of RWS. As a result of the exploratory factor analysis, the KMO statistic was found to be 0.802. In the factor analysis, four factors were determined, and these factors explained 60.023% of the total variance as a result of the analysis performed with the varimax vertical rotation technique (Weaning intention, Baby's readiness, Weaning technique, Mother's readiness). The internal consistency coefficient of the scale was found to indicate a quite high level of reliability (Cronbach's alpha = 0.793).
Shoulder dystocia in deliveries of neonates <3500 grams
Authors: Levin Gabriel , Meyer Raanan , Cahan Tal , Shai Daniel , Tsur Abraham 
Published: October 2023

AbstractObjectivesTo study risk factors for shoulder dystocia (ShD) among women delivering <3500 g newborn.MethodsA retrospective case–control study of all term live‐singleton deliveries during 2011–2019. Women with neonatal birthweight <3500 g were included. We compared cases of ShD to other deliveries by univariate and multivariable regression.ResultsThere were 79/41 092 (0.19%) cases of ShD among neonates <3500 g. In multivariable regression analysis, the following factors were independently associated with ShD; operative vaginal delivery (odds ratio [OR] 2.78; 95% confidence interval [CI]: 1.28–6.02, P = 0.009), vaginal birth after cesarean (VBAC, OR 2.74; 1.22–6.13, P = 0.010), sonographic abdominal circumference to biparietal diameter ratio (3.73 among ShD vs. 3.62, OR 1.35; 95% CI: 1.12–1.63, P = 0.001) and sonographic abdominal circumference to head circumference ratio (1.036 among ShD vs. 1.011, OR 3.04; 95% CI: 1.006–9.23, P = 0.049).ConclusionsThere is an association between operative vaginal delivery and ShD also in deliveries <3500 g. Importantly, the proportions between the fetal head and abdominal circumference are a better predictor of ShD than the newborn fetal weight and VBAC is associated with ShD.
Comparison of the Pharmacokinetic and Pharmacodynamic Activity of Piperacillin and Mezlocillin
Authors: Sullivan Maureen C. , Nightingale Charles H. , Quintiliani Richard , Sweeney Kevin 
Published: October 2023

Study Objective. To compare serum bactericidal activity over time and pharmacokinetics resulting from single doses of piperacillin (PIP) and a single dose of mezlocillin (MEZ).Design. Open‐label, randomized, three‐way crossover study.Setting. Hartford Hospital Clinical Research Center.Patients. Nine healthy volunteers.Interventions. Subjects received single doses of PIP 3 and 4 g/70 kg, and a single dose of MEZ 5 g/70 kg.Measurements and Main Results. Test organisms were two clinical isolates of Pseudomonas aeruginosa. Pharmacodynamic analysis revealed that PIP 4 g had 2‐ to 3‐fold higher peak serum bactericidal activity at the end of infusion and 4‐ to 5‐fold higher activity at 0.5 hour than did MEZ 5 g, and also provided approximately 1 hour additional activity over MEZ 5 g. Pharmacokinetic analysis revealed that serum concentrations resulting from PIP 4 g remained above the minimum inhibitory concentration of our test strains almost twice as long as MEZ 5 g.Conclusion. Since mezlocillin 5 g every 8 hours is currently proving to be effective at many institutions, and since piperacillin 4 g demonstrates superior pharmacokinetic and pharmacodynamic activity, we believe that piperacillin 4 g every 8 hours could be used instead, with resulting cost savings.
Protein3D: Enabling analysis and extraction of metal‐containing sites from the Protein Data Bank with molSimplify
Authors: Edholm Freya , Nandy Aditya , Reinhardt Clorice R. , Kastner David W. , Kulik Heather J. 
Published: October 2023

AbstractMetalloenzymes catalyze a wide range of chemical transformations, with the active site residues playing a key role in modulating chemical reactivity and selectivity. Unlike smaller synthetic catalysts, a metalloenzyme active site is embedded in a larger protein, which makes interrogation of electronic properties and geometric features with quantum mechanical calculations challenging. Here we implement the ability to fetch crystallographic structures from the Protein Data Bank and analyze the metal binding sites in the program molSimplify. We show the usefulness of the newly created protein3D class to extract the local environment around non‐heme iron enzymes containing a two histidine motif and prepare 372 structures for quantum mechanical calculations. Our implementation of protein3D serves to expand the range of systems molSimplify can be used to analyze and will enable high‐throughput study of metal‐containing active sites in proteins.
Genetic counseling clinic model expansion: Impact on access for general genetics clinic
Authors: Doberstein Rachel , Pilipenko Valentina , Pulda Kathleen , Wusik Katie , Spaeth Christine G. 
Published: October 2023

AbstractCincinnati Children's Hospital Medical Center (CCHMC) implemented a Genetic Counseling Clinic (GCC), where the appointment for a general genetics indication is conducted solely by a genetic counselor (GC). We conducted a retrospective chart review of 211 patient encounters scheduled in the GCC between January 1, 2022 and June 30, 2022 and collected patient demographics, wait time, appointment characteristics, referral indication, and clinical recommendations. To study impact on patient access, we compared patient demographics and appointment characteristics with 912 patient encounters scheduled in the General Genetics Clinic with a geneticist during the same time period. We found that there were not significant differences in patient demographics scheduled in the GCC as compared with the General Genetics Clinic with the exception of insurance type, where patients scheduled in the GCC were more likely to have private insurance. Patients scheduled in the GCC had a significantly shorter wait time, were more likely to complete their appointment, were more often new to the genetics division, and were more likely to be seen via telehealth (audio plus video or audio‐only) as compared with patients scheduled in the General Genetics Clinic. The most common indications for patients scheduled in the GCC were post‐test counseling (36.0%) followed by pre‐test counseling and coordination of testing (22.3%), and first‐line testing for autism, intellectual disability, and developmental delay (13.7%). Completed appointments in the GCC often resulted in the GC ordering genetic testing (67.5%). After genetic testing results were received, most patients (72.7%) did not require subsequent follow‐up with the genetics division, thereby reducing burden to the medical genetics team. Our GCC increased access to genetic services and allowed GCs and clinical geneticists to better work at the top of their scope of practice.
The Ritter reaction of N‐(hydroxymethyl)saccharin with nitriles
Authors: de Oliveira Marllon Nascimento , de Mattos Marcio C. S. 
Published: October 2023

AbstractThe development of the Ritter reaction of N‐(hydroxymethyl)saccharin with nitriles for the synthesis of N‐[(saccharinyl)methyl]amides is reported. The success of this reaction relies on an operationally simple procedure and on the use of inexpensive reagents. The present method enables access to a variety of saccharin scaffolds of potential interest in medicinal chemistry in moderate to high yields. Furthermore, the scalability of this reaction was demonstrated by a multigram‐scale transformation, without any loss of efficiency.
Right–Left Ventricular Interdependence in Repaired Tetralogy of Fallot Patients With Right Ventricular Heart Failure
Authors: Jiang Li , Li Yuan , Huang Shan , Han Pei‐Lun , Yan Wei‐Feng , Fang Han , Yang Zhi‐Gang 
Published: October 2023

BackgroundPatients with repaired tetralogy of Fallot (rTOF) continue to face a heightened risk of deteriorating cardiac function, and quantitative techniques of cardiac MRI‐derived cardiac structure and function provide an opportunity to explore the causes and mechanisms of cardiac deterioration.PurposeTo explore right–left ventricular interdependence in rTOF patients before and after the onset of right ventricular (RV) heart failure.Study TypeRetrospective.PopulationOne hundred eighteen rTOF patients (21.85 [16.74, 29.20] years, 58 females) and 34 controls (23.5 [21, 26.5] years, 17 females) that underwent cardiac MRI were analyzed, with rTOF patients being further subdivided into those with preserved RV function (N = 54) and those that experienced RV heart failure (N = 64).Field Strength/Sequence3.0 T/balanced steady‐state free precession sequence.AssessmentRV, left ventricular (LV), and septal strain; RV and LV volume.Statistical TestsChi‐squared tests or Fisher's exact test, One‐way ANOVAs with Bonferroni's post hoc test, Pearson/Spearman correlation, and multivariate backward linear regression analysis. A two‐tailed P < 0.05 was deemed as the significance threshold.ResultsThe MRI‐derived RV, LV, and septal strain decreased sequentially in controls, patients with preserved RV function, and patients with RV heart failure, with a good intra‐observer (0.909–0.964) and inter‐observer (0.879–0.937) agreement. Correlations between LV and RV strain were found to change sequentially with RV function and were the closest in rTOF patients with RV heart failure (r = −0.270 to 0.506). Correlations between RV volume and septal strain was variable in controls (r = 0.483 to −0.604), patients with preserved RV function (r = −0.034 to −0.295), and patients with RV heart failure (r = −0.026 to 0.500). Multivariate analyses revealed that the RV longitudinal strain was independently correlated with LV strain in three directions in rTOF patients with RV heart failure (Radial −0.70 [−1.33, −0.06]; Circumferential 0.44 [0.17, 0.72]; Longitudinal 0.54 [0.26, 0.81]).Data ConclusionIn rTOF patients, the coupling between RV volume and septal strain was broken during RV function compensation, and the adverse effect of RV on LV deformation was highest in patients with RV heart failure.Evidence Level4Technical EfficacyStage 5
Cartilaginous endplates: A comprehensive review on a neglected structure in intervertebral disc research
Authors: Crump Katherine B. , Alminnawi Ahmad , Bermudez‐Lekerika Paola , Compte Roger , Gualdi Francesco , McSweeney Terence , Muñoz‐Moya Estefano , Nüesch Andrea , Geris Liesbet , Dudli Stefan , Karppinen Jaro , Noailly Jérôme , Le Maitre Christine , Gantenbein Benjamin 
Published: October 2023

AbstractThe cartilaginous endplates (CEP) are key components of the intervertebral disc (IVD) necessary for sustaining the nutrition of the disc while distributing mechanical loads and preventing the disc from bulging into the adjacent vertebral body. The size, shape, and composition of the CEP are essential in maintaining its function, and degeneration of the CEP is considered a contributor to early IVD degeneration. In addition, the CEP is implicated in Modic changes, which are often associated with low back pain. This review aims to tackle the current knowledge of the CEP regarding its structure, composition, permeability, and mechanical role in a healthy disc, how they change with degeneration, and how they connect to IVD degeneration and low back pain. Additionally, the authors suggest a standardized naming convention regarding the CEP and bony endplate and suggest avoiding the term vertebral endplate. Currently, there is limited data on the CEP itself as reported data is often a combination of CEP and bony endplate, or the CEP is considered as articular cartilage. However, it is clear the CEP is a unique tissue type that differs from articular cartilage, bony endplate, and other IVD tissues. Thus, future research should investigate the CEP separately to fully understand its role in healthy and degenerated IVDs. Further, most IVD regeneration therapies in development failed to address, or even considered the CEP, despite its key role in nutrition and mechanical stability within the IVD. Thus, the CEP should be considered and potentially targeted for future sustainable treatments.
Simultaneous determination and pharmacokinetics study of three triterpenoid saponins in rat plasma by ultra‐high‐performance liquid chromatography tandem mass‐spectrometry after oral administration of Astragalus Membranaceus leaf extract
Authors: Wang Zhibin , Borjigin Gilwa , Zhang Mingyu , Yang Chunjuan , Wang Zhenyue , Kuang Haixue 
Published: October 2023

A selective and sensitive ultra‐high‐performance liquid chromatography‐tandem mass spectrometry method was developed and validated for the determination of three triterpenoid saponins isolated from Astragalus membranaceus leaf extract. In this article, a method for simultaneous determination of Huangqiyenin A, Huangqiyenin E, and Huangqiyenin K was established for the first time. The method was successfully applied to the pharmacokinetic study of Astragalus membranaceus leaf extract after oral administration. Liquid–liquid extraction was applied to plasma sample preparation. Multiple reaction monitoring mode with an electrospray ion source in positive electrospray ionization was chosen to quantify the analytes. Chromatographic separation was performed on a Waters HSS T3 column, using gradient elution with a mobile phase composed of acetonitrile and 5 mM ammonium acetate/water. The pharmacokinetic results showed that all three compounds had the characteristics of rapid absorption‐slow metabolism trend. The time of maximum plasma concentration of Huangqiyenin A is higher than Huangqiyenin E and Huangqiyenin K. And the maximum plasma concentration of Huangqiyenin A is higher as well.The pharmacokinetic results revealed the pharmacokinetic characteristics of the three analytes in rat plasma, which could provide a helpful reference for the further study of Astragalus membranaceus leaf extract.
Dynamic capabilities and asset orchestration
Authors: Kodama Mitsuru 
Published: October 2023

AbstractIn recent years, the theory of dynamic capabilities (DC) has become more sophisticated and has become a framework for sustainable growth through strategic innovation in companies. The “asset orchestration” function, a core concept of DC, connects various types of knowledge (assets) in an entrepreneurial manner and realizes the recombination, modification, and transformation of existing knowledge (assets) for the purpose of developing new businesses, new products, and so forth. However, the dynamic mechanism of such asset orchestration is largely unclarified in previous studies. This paper derives a dynamic theoretical model of asset orchestration and the components of DC necessary for companies to respond to the uncertainty of business environments and the speed of environmental change. Using the findings of the derived theoretical model, this paper analyzes in‐depth case studies of Taiwan Semiconductor Manufacturing Company, which is currently attracting worldwide attention as a core company in the semiconductor industry, to verify the validity of the theoretical model.
Methylation of ESR1 promoter induced by SNAI2–DNMT3B complex promotes epithelial–mesenchymal transition and correlates with poor prognosis in ERα‐positive breast cancers
Authors: Li Ji‐Wei , Deng Qiu‐Min , Zhu Jian‐Ling , Min Wei , Hu Xiao‐Yi , Yu Chen Hong‐ , Luo Zhong , Lin Lin‐Ling , Wei Xiao‐Long , Zhang Yong‐Qu , Lou Kang‐Liang , Gao Yi‐Yang , Zhang Guo‐Jun , Bai Jing‐Wen 
Published: October 2023

AbstractEstrogen receptor α (ERα) serves as an essential therapeutic predictor for breast cancer (BC) patients and is regulated by epigenetic modification. Abnormal methylation of cytosine phosphoric acid guanine islands in the estrogen receptor 1 (ESR1) gene promoter could silence or decrease ERα expression. In ERα‐negative BC, we previously found snail family transcriptional repressor 2 (SNAI2), a zinc‐finger transcriptional factor, recruited lysine‐specific demethylase 1 to the promoter to transcriptionally suppress ERα expression by demethylating histone H3 lysine 4 dimethylation (H3K4me2). However, the role of SNAI2 in ERα‐positive BC remains elusive. In this study, we observed a positive correlation between SNAI2 and ESR1 methylation, and SNAI2 promoted ESR1 methylation by recruiting DNA methyltransferase 3 beta (DNMT3B) rather than DNA methyltransferase 1 (DNMT1) in ERα‐positive BC cells. Subsequent enrichment analysis illustrated that ESR1 methylation is strongly correlated with cell adhesion and junction. Knocking down DNMT3B could partially reverse SNAI2 overexpression‐induced cell proliferation, migration, and invasion. Moreover, high DNMT3B expression predicted poor relapse‐free survival and overall survival in ERα‐positive BC patients. In conclusion, this study demonstrated the novel mechanisms of the ESR1 methylation mediated with the SNAI2/DNMT3B complex and enhanced awareness of ESR1 methylation's role in promoting epithelial–mesenchymal transition in BC.
Copper and Diabetes: Current Research and Prospect
Authors: Chang Wenguang , Li Peifeng 
Published: October 2023

AbstractCopper is an essential trace metal for normal cellular functions; a lack of copper is reported to impair the function of important copper‐binding enzymes, while excess copper could lead to cell death. Numerous studies have shown an association between dietary copper consumption or plasma copper levels and the incidence of diabetes/diabetes complications. And experimental studies have revealed multiple signaling pathways that are triggered by copper shortages or copper overload in diabetic conditions. Moreover, studies show that treated with copper chelators improve vascular function, maintain copper homeostasis, inhibit cuproptosis, and reduce cell toxicity, thereby alleviating diabetic neuropathy, retinopathy, nephropathy, and cardiomyopathy. However, the mechanisms reported in these studies are inconsistent or even contradictory. This review summarizes the precise and tight regulation of copper homeostasis processes, and discusses the latest progress in the association of diabetes and dietary copper/plasma copper. Further, the study pays close attention to the therapeutic potential of copper chelators and copper in diabetes and its complications, and hopes to provide new insight for the treatment of diabetes.
Parent‐child agreement on children's psychopathology and the impact of parental depression
Authors: Löchner Johanna , Hämmerle Stephanie , Ghezih Sarah , Starman‐Wöhrle Kornelija , Schulte‐Körne Gerd , Platt Belinda 
Published: October 2023

AbstractBackgroundParental depression increases children's risk of mental illness and may simultaneously impair the detection of children's symptoms. Here we investigate the nature of parent‐child agreement of children's psychopathology in children of parents with current (cMD) versus remitted (rMD) major depression.MethodsBaseline data from 100 parent‐child dyads including healthy children aged 8–17 (M = 11.89, SD = 2.83) and their parents with a history of depression were analysed. The presence of sub‐clinical psychopathology (yes/no) in children was assessed using semi‐structured diagnostic interviews with child and parent (K‐DIPS). Self‐ (YSR) and parent‐report (CBCL) questionnaires were used to measure the severity of symptoms. Parent‐child agreement was calculated using Chi‐square tests and Cohen's kappa respectively. We compared whether agreement differed between children of parents with cMD (n = 52) versus rMD (n = 48).ResultsIn the interviews parents more frequently reported sub‐clinical child psychopathology than the children themselves (χ2 1,100 = 4.63, p < 0.001, d = 0.59). This pattern characterised parents with cMD (χ2 1,52 = 7.99, p = 0.005; κ = 0.582) but not rMD (χ2 1,48 = 000, p = 0.686; κ = −0.010), a difference which was statistically significant (z = 3.14, p < 0.001, d = 0.66).ConclusionSince agreement between parents and children about the severity of children's symptoms was particularly poor in families where parents were currently depressed, parental mental illness should be taken into account when assessing youth psychopathology.
Skeletal muscle injury in COVID infection: Frequency and patterns
Authors: Rajput Saurabh Singh , Aghoram Rajeswari , Wadwekar Vaibhav , Nanda Nivedita 
Published: October 2023

AbstractIntroduction/AimsLittle is known about skeletal muscle injury with coronavirus disease 2019 (COVID‐19). We estimate the frequency and explore the patterns of skeletal muscle injury in acute COVID‐19.MethodsA cohort of COVID patients with mild to moderate symptoms were evaluated in a COVID‐designated hospital between May and December 2021 and followed for 2 weeks. Skeletal muscle injury was assessed according to creatine kinase (CK) levels, Manual Muscle Test‐8 (MMT‐8) score, and the Health Assessment Questionnaire (HAQ) score. Injury was defined as CK >200 IU/L with an MMT‐8 score < 76. The association between such injury and severity and outcomes were evaluated using cross‐tabulations.ResultsTwo hundred fifty participants with a mean age of 50.2 years (SD: 17.2) were included. One hundred nine (43.6%) were women; 84 (34%) developed severe disease. Median CK levels were 91 IU/L (IQR 56–181). [Correction added on 17 November 2023, after first online publication: In the preceding sentence, the IQR was corrected from ‘56,181’.] Patients with weakness on the MMT‐8 (n = 247, 98.8%) and disability on the HAQ (n = 107; 42.8%) were common. Neck flexor muscles were prominently affected. Skeletal muscle injury was seen in 22.4% (95% CI: 17.4–28.1). There was no significant association between skeletal muscle injury and maximal severity of illness or short‐term outcomes. Disability increased over 14 days in most survivors (n = 172, 72.3%) and this was not seen in those with mild disease (OR: 0.4, 95% CI: 0.22–0.70).DiscussionSkeletal muscle injury appears to be common in people presenting with mild to moderate COVID infection.