bluuebunny/crossref_metadata_2025_split huggingface dataset:
Issues in Contemporary Drug Delivery
Authors: Chotidiloke Chadanapis , Elking Paulette , Banakar Umesh V. 
Published: April 2023

Objective To provide an overview of rheumatoid arthritis (RA) and the medications presently being used to treat the disease. Data Sources References have been selected from published articles, monographs, manufacturers’ product information, textbooks on therapeutics of rheumatic diseases, and specific computerized databases such as DRUGDEX. Study Selection Studies that establish the pharmacokinetics of the various drugs have been included, as have comparative studies of the various agents. Studies that gave specifics concerning the use of the various agents in the elderly were given priority in selection. Monographs from both United States Pharmacopeia Dispensing Information and American Hospital Formulary Service Drug Information ‘92 were used to ensure consistency in dosing and pharmacokinetic data. Data Synthesis A variety of medications are used to treat RA, and are classified according to their ability to alleviate the inflammatory process and symptomatology of the disease, or to actually slow down or halt the progression of the disease process itself. The long-established pyramidal approach to therapy is presently being challenged so as to employ the slow-acting or disease-modifying agents earlier in the process. Conclusions A wide variety of medications are presently available for treating RA. As the pathogenesis of the disease becomes better defined, it is hoped that less-toxic and more-specific and -effective therapies will become available. Medications remain the cornerstone of therapy; however, patient education, rest, and exercise are equally important.
Graphic Analysis of First-Order Rate Data
Authors: Hermann Joachim J. 
Published: April 2023

Objective To provide an in-depth discussion of five graphs used to analyze first-order rate data. Special emphasis is given to the use of semilogarithmic graph paper and semilogarithmic plots. Data Sources A theoretical set of time-concentration data was generated using the equation C=Co e-kt. Arbitrarily chosen values of 6.0 mg/L and 0.33 h-1 were used for Co and k, respectively. Study Selection First-order rate data were plotted for subsequent graphic analysis in five different ways: concentration (C) versus time (t) (on linear graph paper), ln C versus t (on linear graph paper), log C versus t (on linear graph paper), C versus t (on commercial semilogarithmic graph paper), and C versus t (on extemporaneously prepared semilogarithmic graph paper). Data Synthesis Methodology for estimation of the first-order rate constant, half-life, and initial concentration from each of the five different graphs is discussed. The strengths and weaknesses of each graphing technique are presented. Fundamental equations relevant to first-order kinetics are also reviewed. Familiarity with these equations is shown to be essential to the analysis of different graphs. Conclusions Each of the five plots used to analyze the first-order rate data offers advantages and disadvantages. The most expedient approach is the use of commercially available semilogirithmic graph paper.
CircRNF10-DHX15 interaction suppressed breast cancer progression by antagonizing DHX15-NF-κB p65 positive feedback loop
Authors: Zheng Wenfang , Wang Xuehui , Yu Yunhe , Ji Changle , Fang Lin 
Published: April 2023

Abstract
Background
Breast cancer (BC) is a common threat to women. The continuous activation of nuclear factor kappa B (NF-κB) signaling pathway contributes to the development of BC. This study aimed to investigate the role of a circular RNA (circRNF10) in BC progression and regulating NF-κB signaling pathway.

Methods
Bioinformatics analysis, RT-qPCR, subcellular fractionation, FISH, RNase R treatment, and actinomycin D assay were used to explore the expression and characteristics of circRNF10 in BC. The biological functions of circRNF10 in BC were analyzed by MTT assay, colony formation assay, wound healing assay, and Transwell assay. RNA pulldown and RIP assay were used to identify the interaction between circRNF10 and DEAH (Asp-Glu-Ala-His) box helicase 15 (DHX15). The impact of circRNF10-DHX15 interaction on NF-κB signaling pathway was explored by western blot, IF, and co-IP. Furthermore, dual-luciferase reporter assay, ChIP, and EMSA were performed to assess the effect of NF-κB p65 on DHX15 transcription.

Results
CircRNF10 was downregulated in BC, and lower expression of circRNF10 was related to poor prognosis of patients with BC. CircRNF10 inhibited the proliferation and migration of BC. Mechanically, circRNF10-DHX15 interaction sequestered DHX15 from NF-κB p65, thereby inhibiting the activation of NF-κB signaling pathway. On the other hand, NF-κB p65 enhanced DHX15 transcription by binding to the promoter of DHX15. Altogether, circRNF10 impaired the DHX15-NF-κB p65 positive feedback loop and suppressed the progression of BC.

Conclusion
CircRNF10-DHX15 interaction suppressed the DHX15-NF-κB p65 positive feedback loop, thereby inhibiting BC progression. These findings provide new insights in the continuous activation of NF-κB signaling pathway and raised potential therapeutic approach for BC treatment.
DGH-GO: dissecting the genetic heterogeneity of complex diseases using gene ontology
Authors: Asif Muhammad , Martiniano Hugo F. M. C. , Lamurias Andre , Kausar Samina , Couto Francisco M. 
Published: April 2023

Abstract
Background
Complex diseases such as neurodevelopmental disorders (NDDs) exhibit multiple etiologies. The multi-etiological nature of complex-diseases emerges from distinct but functionally similar group of genes. Different diseases sharing genes of such groups show related clinical outcomes that further restrict our understanding of disease mechanisms, thus, limiting the applications of personalized medicine approaches to complex genetic disorders.

Results
Here, we present an interactive and user-friendly application, called DGH-GO. DGH-GO allows biologists to dissect the genetic heterogeneity of complex diseases by stratifying the putative disease-causing genes into clusters that may contribute to distinct disease outcome development. It can also be used to study the shared etiology of complex-diseases. DGH-GO creates a semantic similarity matrix for the input genes by using Gene Ontology (GO). The resultant matrix can be visualized in 2D plots using different dimension reduction methods (T-SNE, Principal component analysis, umap and Principal coordinate analysis). In the next step, clusters of functionally similar genes are identified from genes functional similarities assessed through GO. This is achieved by employing four different clustering methods (K-means, Hierarchical, Fuzzy and PAM). The user may change the clustering parameters and explore their effect on stratification immediately. DGH-GO was applied to genes disrupted by rare genetic variants in Autism Spectrum Disorder (ASD) patients. The analysis confirmed the multi-etiological nature of ASD by identifying four clusters of genes that were enriched for distinct biological mechanisms and clinical outcome. In the second case study, the analysis of genes shared by different NDDs showed that genes causing multiple disorders tend to aggregate in similar clusters, indicating a possible shared etiology.

Conclusion
DGH-GO is a user-friendly application that allows biologists to study the multi-etiological nature of complex diseases by dissecting their genetic heterogeneity. In summary, functional similarities, dimension reduction and clustering methods, coupled with interactive visualization and control over analysis allows biologists to explore and analyze their datasets without requiring expert knowledge on these methods. The source code of proposed application is available at https://github.com/Muh-Asif/DGH-GO
Optimization of fermentation conditions for surfactin production by B. subtilis YPS-32
Authors: Zhou Yingjun , Yang Xiaoxue , Li Qing , Peng Zheng , Li Jianghua , Zhang Juan 
Published: April 2023

Abstract
Background
Surfactin produced by microbial fermentation has attracted increasing attention because of its low toxicity and excellent antibacterial activity. However, its application is greatly limited by high production costs and low yield. Therefore, it is important to produce surfactin efficiently while reducing the cost. In this study, B. subtilis strain YPS-32 was used as a fermentative strain for the production of surfactin, and the medium and culture conditions for the fermentation of B. subtilis YPS-32 for surfactin production were optimized.

Results
First, Landy 1 medium was screened as the basal medium for surfactin production by B. subtilis strain YPS-32. Then, using single-factor optimization, the optimal carbon source for surfactin production by B. subtilis YPS-32 strain was determined to be molasses, nitrogen sources were glutamic acid and soybean meal, and inorganic salts were KCl, K2HPO4, MgSO4, and Fe2(SO4)3. Subsequently, using Plackett-Burman design, MgSO4, time (h) and temperature (°C) were identified as the main effect factors. Finally, Box-Behnken design were performed on the main effect factors to obtain optimal fermentation conditions: temperature of 42.9 °C, time of 42.8 h, MgSO4 = 0.4 g·L− 1. This modified Landy medium was predicted to be an optimal fermentation medium: molasses 20 g·L− 1, glutamic acid 15 g·L− 1, soybean meal 4.5 g·L− 1, KCl 0.375 g·L− 1, K2HPO4 0.5 g·L− 1, Fe2(SO4)3 1.725 mg·L− 1, MgSO4 0.4 g·L− 1. Using the modified Landy medium, the yield of surfactin reached 1.82 g·L− 1 at pH 5.0, 42.9 ℃, and 2% inoculum for 42.8 h, which was 2.27-fold higher than that of the Landy 1 medium in shake flask fermentation. Additionally, under these optimal process conditions, further fermentation was carried out at the 5 L fermenter level by foam reflux method, and at 42.8 h of fermentation, surfactin reached a maximum yield of 2.39 g·L− 1, which was 2.96-fold higher than that of the Landy 1 medium in 5 L fermenter.

Conclusion
In this study, the fermentation process of surfactin production by B. subtilis YPS-32 was improved by using a combination of single-factor tests and response surface methodology for test optimization, which laid the foundation for its industrial development and application.
Epidemiology of clinically isolated methicillin-resistant Staphylococcus aureus (MRSA) and its susceptibility to linezolid and vancomycin in Egypt: a systematic review with meta-analysis
Authors: Azzam Ahmed , Khaled Heba , Mosa Maha , Refaey Neveen , AlSaifi Mohammed , Elsisi Sarah , Elagezy Fatma Khaled , Mohsen May 
Published: April 2023

AbstractBackgroundMethicillin-resistantStaphylococcus aureus(MRSA) is a major nosocomial pathogen that causes severe morbidity and mortality worldwide. For the establishment of national strategies to combat MRSA infection in each country, accurate and current statistics characterizing the epidemiology of MRSA are essential. The purpose of this study was to determine the prevalence of MRSA amongStaphylococcus aureusclinical isolates in Egypt. In addition, we aimed to compare different diagnostic methods for MRSA and determine the pooled resistance rate of linezolid and vancomycin to MRSA. To address this knowledge gap, we conducted a systematic review with meta-analysis.MethodsA comprehensive literature search from inception to October 2022 of the following databases was performed: MEDLINE [PubMed], Scopus, Google Scholar, and Web of Science. The review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) Statement. Based on the random effects model, results were reported as proportions with a 95% confidence interval (CI). Analyses of the subgroups were conducted. A sensitivity analysis was conducted to test the robustness of the results.ResultsA total of sixty-four (64) studies were included in the present meta-analysis, with a total sample size of 7171 subjects. The overall prevalence of MRSA was 63% [95% CI: 55–70]. Fifteen (15) studies used both PCR and cefoxitin disc diffusion for MRSA detection, with a pooled prevalence rate of 67% [95% CI: 54–79] and 67% [95% CI: 55–80], respectively. While nine (9) studies used both PCR and Oxacillin disc diffusion for MRSA detection, the pooled prevalences were 60% [95% CI: 45–75] and 64% [95% CI: 43–84], respectively. Furthermore, MRSA appeared to be less resistant to linezolid than vancomycin, with a pooled resistance rate of 5% [95% CI: 2–8] to linezolid and 9% [95% CI: 6–12] to vancomycin, respectively.ConclusionOur review highlights Egypt's high MRSA prevalence. The cefoxitin disc diffusion test results were found to be consistent with PCR identification of themecAgene. A prohibition on antibiotic self-medication and efforts to educate healthcare workers and patients about the proper use of antimicrobials may be required to prevent further increases.
Diagnostic value of neutrophil gelatinase-associated lipocalin (NGAL) as an early biomarker for detection of renal failure in hypertensives: a case–control study in a regional hospital in Ghana
Authors: Danquah Mark , Owiredu William K. B. A. , Jnr B. A. Eghan , Serwaa Dorcas , Odame Anto Enoch , Peprah Maxwell Owusu , Obirikorang Christian , Fondjo Linda A. 
Published: April 2023

AbstractBackgroundRenal failure is one of the most serious vascular effects of hypertension. For better therapy and prevention of complications, early kidney disease identification in these patients is absolutely essential. However, current studies have proposed plasma Neutrophil Gelatinase Associated Lipocalin (pNGAL) to be a better biomarker comparative to serum creatinine (SCr). This study assessed the diagnostic utility of plasma neutrophil gelatinase-associated lipocalin (pNGAL) as a biomarker for early nephropathy diagnosis in hypertensive individuals.MethodsThis hospital-based case–control study comprised 140 hypertensives and 70 healthy participants. A well-structured questionnaire and patient case notes were used to document relevant demographic and clinical information. 5 ml of venous blood sample was taken to measure fasting blood sugar levels, creatinine, and plasma NGAL levels. All data were analyzed using the Statistical Package for Social Sciences (SPSS release 20.0, copyrite©SPSS Inc.) and ap-value < 0.05 was considered statistically significant.ResultsIn this study the plasma neutrophil gelatinase-associated lipocalin (NGAL) levels were significantly higher in cases compared to controls. Hypertensive cases also had significantly higher waist-circumference compared to the control group. The median fasting blood sugar level was significantly higher in cases compared to controls. This study established the use of Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Cockcroft and Gault formula (CG) as the most accurate predictive equations for assessing renal dysfunction. The threshold for NGAL above which renal impairment can be assessed was found to be 109.4 ng/ml (sen-91%, spec. – 68%), 120 ng/ml (sen- 100%, spec- 72%) and 118.6 ng/ml (sen- 83%, spec- 72%) for MDRD, CKD-EPI and CG equations respectively. The prevalence of CKD was 16.4%, 13.6% and 20.7% respectively using the MDRD, CKD-EPI and CG.ConclusionFrom this study, pNGAL is a better indicator of kidney impairment in the early stages of CKD as compared with sCr in general hypertensive population.
Use of pregnancy personalised follow-up in case of maternal social vulnerability to reduce prematurity and neonatal morbidity
Authors: Crequit Simon , Bierry Gregory , Maria Perbellini , Bouali Sakina , La Tour Adelaïde Dupre , Sgihouar Naima , Renevier Bruno 
Published: April 2023

Abstract
Background
Social deprivation is a major risk factor of adverse pregnancy outcomes. Yet, there is few studies evaluating interventions aiming at reducing the impact of social vulnerability on pregnancy outcomes.

Objective
To compare pregnancy outcomes between patients that received personalized pregnancy follow-up (PPFU) to address social vulnerability versus standard care.

Methods
Retrospective comparative cohort in a single institution between 2020 and 2021. A total of 3958 women with social vulnerability that delivered a singleton after 14 gestational weeks were included, within which 686 patients had a PPFU. Social vulnerability was defined by the presence of at least one of the following characteristics: social isolation, poor or insecure housing conditions, no work-related household income, and absence of standard health insurance (these four variables were combined as a social deprivation index (SDI)), recent immigration (< 12 month), interpersonal violence during pregnancy, being handicaped or minor, addiction during pregnancy. Maternal characteristics and pregnancy outcomes were compared between patients that received PPFU versus standard care. The associations between poor pregnancy outcomes (premature birth before 37 gestational weeks (GW), premature birth before 34 GW, small for gestational age (SGA) and PPFU were tested using multivariate logistic regression and propensity score matching.

Results
After adjustment on SDI, maternal age, parity, body mass index, maternal origin and both high medical and obstetrical risk level before pregnancy, PPFU was an independent protective factor of premature birth before 37 gestational weeks (GW) (aOR = 0.63, 95%CI[0.46–0.86]). The result was similar for premature birth before 34 GW (aOR = 0.53, 95%CI [0.34–0.79]). There was no association between PPFU and SGA (aOR = 1.06, 95%CI [0.86 – 1.30]). Propensity score adjusted (PSa) OR for PPFU using the same variables unveiled similar results, PSaOR = 0.63, 95%CI[0.46–0.86] for premature birth before 37 GW, PSaOR = 0.52, 95%CI [0.34–0.78] for premature birth before 34 GW and PSaOR = 1.07, 95%CI [0.86 – 1.33] for SGA.

Conclusions
This work suggests that PPFU improves pregnancy outcomes and emphasizes that the detection of social vulnerability during pregnancy is a major health issue.
Impact of maternal body mass index on outcomes of singleton pregnancies after assisted reproductive technology: a 14-year analysis of the US Nationwide Inpatient Sample
Authors: Li Yi-Ping , Li Wei-Jiun , Hsieh Wen-Chi , Chen Li-Shan , Yu Cheng-Wei 
Published: April 2023

Abstract
Background
Obesity is increasing globally, which affects multiple human functions, including reproductive health. Many women with overweight and obesity of child-bearing years are treated with assisted reproductive technology (ART). However, the clinical impact of body mass index (BMI) on pregnancy outcomes after ART remains to be determined. Therefore, this population-based retrospective cohort study aimed to assess whether and how higher BMI affects singleton pregnancy outcomes.

Methods
This study used the large nationally representative database of the US National Inpatient Sample (NIS), extracting data of women with singleton pregnancies who had received ART from 2005 to 2018. Diagnostic codes of the International Classification of Diseases, Ninth and Tenth edition (ICD-9 and ICD-10) were used to identify females admitted to US hospitals with delivery-related discharge diagnoses or procedures and secondary diagnostic codes for ART, including in vitro fertilization. The included women were further categorized into three groups based on BMI values < 30, 30–39, and ≥ 40 kg/m2. Univariate and multivariable regression analysis were conducted to assess the associations between study variables and maternal and fetal outcomes.

Results
Data of totally 17,048 women were included in the analysis, which represented a population of 84,851 women in the US. Number of women in the three BMI groups were 15, 878 (BMI < 30 kg/m2), 653 (BMI 30–39 kg/m2), and 517 (BMI ≥ 40 kg/m2), respectively. The multivariable regression analysis revealed that, compared to BMI < 30 kg/m2, BMI 30–39 kg/m2 was significantly associated with increased odds for pre-eclampsia and eclampsia (adjusted OR = 1.76, 95% CI = 1.35, 2.29), gestational diabetes (adjusted OR = 2.25, 95% CI = 1.70, 2.98), and Cesarean delivery (adjusted OR = 1.36, 95% CI = 1.15, 1.60). Further, BMI ≥ 40 kg/m2 was associated with greater odds for pre-eclampsia and eclampsia (adjusted OR = 2.25, 95% CI = 1.73, 2.94), gestational diabetes (adjusted OR = 3.64, 95% CI = 2.80, 4.72), disseminated intravascular coagulation (DIC) (adjusted OR = 3.79, 95% CI = 1.47, 9.78), Cesarean delivery (adjusted OR = 1.85, 95% CI = 1.54, 2.23), and hospital stay ≥ 6 days (adjusted OR = 1.60, 95% CI = 1.19, 2.14). However, higher BMI was not significantly associated with greater risk of the fetal outcomes assessed.

Conclusions
Among US pregnant women who received ART, having a higher BMI level independently increases the risk for adverse maternal outcomes such as pre-eclampsia and eclampsia, gestational diabetes, DIC, longer hospital stays, and higher rates of Cesarean delivery, while risk is not increased for fetal outcomes.
Impact of pharmacogenomic DPYD variant guided dosing on toxicity in patients receiving fluoropyrimidines for gastrointestinal cancers in a high-volume tertiary centre
Authors: Lau David K. , Fong Caroline , Arouri Faten , Cortez Lillian , Katifi Hannah , Gonzalez-Exposito Reyes , Razzaq Muhammad Bilal , Li Su , Macklin-Doherty Aislinn , Hernandez Monica Arenas , Hubank Michael , Fribbens Charlotte , Watkins David , Rao Sheela , Chau Ian , Cunningham David , Starling Naureen 
Published: April 2023

AbstractBackgroundDihydropyrimidine dehydrogenase (DPD) is a key enzyme in the metabolism of fluoropyrimidines. Variations in the encodingDPYDgene are associated with severe fluoropyrimidine toxicity and up-front dose reductions are recommended. We conducted a retrospective study to evaluate the impact of implementingDPYDvariant testing for patients with gastrointestinal cancers in routine clinical practice in a high volume cancer centre in London, United Kingdom.MethodsPatients receiving fluoropyrimidine chemotherapy for gastrointestinal cancer prior to, and following the implementation ofDPYDtesting were identified retrospectively. After November 2018, patients were tested forDPYDvariants c.1905+1G>A (DPYD*2A), c.2846A>T (DPYDrs67376798), c.1679T>G (DPYD*13), c.1236G>A (DPYDrs56038477), c.1601G>A (DPYD*4) prior to commencing fluoropyrimidines alone or in combination with other cytotoxics and/or radiotherapy. Patients with aDPYDheterozygous variant received an initial dose reduction of 25–50%. Toxicity by CTCAE v4.03 criteria was compared betweenDPYDheterozygous variant and wild type carriers.ResultsBetween 1stDecember 2018 and 31stJuly 2019, 370 patients who were fluoropyrimidine naïve underwent aDPYDgenotyping test prior to receiving a capecitabine (n = 236, 63.8%) or 5FU (n = 134, 36.2%) containing chemotherapy regimen. 33 patients (8.8%) were heterozygousDPYDvariant carriers and 337 (91.2%) were wild type. The most prevalent variants were c.1601G > A (n = 16) and c.1236G > A (n = 9). Mean relative dose intensity for the first dose was 54.2% (range 37.5–75%) forDPYDheterozygous carriers and 93.2% (42.9–100%) forDPYDwild type carriers. Overall grade 3 or worse toxicity was similar inDPYDvariant carriers (4/33, 12.1%) as compared to wild-type carriers (89/337, 25.7%;P = 0.0924).ConclusionsOur study demonstrates successful routineDPYDmutation testing prior to the initiation of fluoropyrimidine chemotherapy with high uptake. In patients withDPYDheterozygous variants with pre-emptive dose reductions, high incidence of severe toxicity was not observed. Our data supports routineDPYDgenotype testing prior to commencement of fluoropyrimidine chemotherapy.