bluuebunny/crossref_metadata_2025_split huggingface dataset:
Body weight changes in patients with type 2 diabetes and a recent acute coronary syndrome: an analysis from the EXAMINE trial
Authors: Ferreira João Pedro , Rossignol Patrick , Bakris George , Mehta Cyrus , White William B. , Zannad Faiez 
Published: September 2021

Abstract
Background
Patients with type 2 diabetes (T2D) may experience frequent body weight changes over time. The prognostic impact of these weight changes (gains or losses) requires further study.

Aims
To study the associations between changes in body weight (intentional or unintentional) with subsequent outcomes.

Methods
The EXAMINE trial included 5380 patients with T2D and a recent acute coronary syndrome, who were randomized to alogliptin or placebo. Time-updated Cox models and mixed effects models were used to test the associations between changes in body weight and subsequent outcomes over a median follow-up of 1.6 (1.0–2.1) years.

Results
During the post-randomization follow-up period, 1044 patients (19.4%) experienced a weight loss ≥ 5% of baseline weight, 2677 (49.8%) had a stable weight, and 1659 (30.8%) had a ≥ 5 % weight gain. Patients with weight loss were more frequently women and had more co-morbid conditions. In contrast, patients who gained ≥ 5% weight were more frequently men with less co-morbid conditions. A weight loss ≥ 5% was independently associated with a higher risk of subsequent adverse outcomes, including all-cause mortality: adjusted HR (95% CI) = 1.79 (1.33–2.42), P < 0.001. Similar associations were found for cardiovascular mortality, the composite of cardiovascular mortality or heart failure hospitalization, and the primary outcome. A weight gain ≥ 5% was independently associated with an increase in the risk of subsequent cardiovascular mortality or heart failure hospitalization only: adjusted HR (95% CI) = 1.34 (1.02–1.76), P = 0.033.

Conclusions
In patients with T2D who had a recent ACS/MI, a ≥ 5% loss of body weight was associated with a higher risk of subsequent cardiovascular events and mortality.
Comprehensive analysis of angiogenesis subtype of squamous cell carcinoma
Authors: Qin Fanglu , Lin Shenghua , Deng Kun , Qin Junqi , Xu Zhanyu , Yuan Liqiang , Wei Jiangbo , Sun Yu , Zheng Tiaozhan , Li Shikang 
Published: September 2021

Abstract
Background
Squamous cell carcinoma (SCC) is a disease with distinct management complexities as it displays a remarkably heterogeneous molecular subtype. However, the landscape of angiogenesis for SCC is not fully investigated.

Method and materials
The angiogenesis-related subtypes of SCC were established by using the ConsensusClusterPlus package based on angiogenesis-related genes and TCGA data. We analyzed the alteration of genes and miRNAs as well as pathways associated with angiogenesis subtypes. Next, the regulation network, the correlation with genomic characteristics, immune microenvironment, and clinical features of the angiogenesis subtypes were further investigated. Finally, the prognostic impact of the angiogenesis-related subtypes for SCC was also analyzed.

Results
A total of 1368 SCC samples were included in this study. Two angiogenesis subtypes were then identified based on the one hundred and sixty-three angiogenesis-related genes with subtype1 (angiogenesis subtype) of 951 SCC patients and subtype2 (non-angiogenesis subtype) of 417 SCC. GSEA revealed that angiogenesis and epithelial-mesenchymal transition, inflammatory response, and hypoxia were enriched in the angiogenesis subtype. Eight of the 15 immune checkpoints (ADORA2A, BTLA, CD276, CYBB, HAVCR2, SIGLEC7, SIGLEC9, and VTCN1) were significantly upregulated while C10orf54 were significantly downregulated in the angiogenesis subtype. The survival analysis revealed that the patients in the angiogenesis subtype have poorer survival outcomes than those in the non-angiogenesis subtype (P = 0.017 for disease-free interval and P = 0.00013 for overall survival).

Conclusion
Our analysis revealed a novel angiogenesis subtype classification in SCC and provides new insights into a hallmark of SCC progression.
Sequential cleavage and blastocyst embryo transfer and IVF outcomes: a systematic review
Authors: Zhang Jianeng , Wang Chong , Zhang Huanhuan , Zhou Yan 
Published: September 2021

AbstractBackgroundSequential embryo transfer has been proposed as a way to improve embryo implantation in women forin vitrofertilization (IVF), but the effect on pregnancy outcomes remains ambiguous. This systematic review was conducted to investigate the efficacy of sequential embryo transfer on IVF outcomes.MethodsA literature search was performed in the PubMed, Web of Science, Cochrane Library, ScienceDirect and Wanfang databases. Data were pooled using a random- or fixed-effects model according to study heterogeneity. The results are expressed as relative risks (RRs) with 95% confidence intervals (CIs). Heterogeneity was evaluated by the I2statistic. The study protocol was registered prospectively on INPLASY, ID: INPLASY202180019.ResultsTen eligible studies with 2658 participants compared sequential embryo transfer and cleavage transfer, while four studies with 513 participants compared sequential embryo transfer and blastocyst transfer. The synthesis results showed that the clinical pregnancy rate was higher in the sequential embryo transfer group than in the cleavage embryo transfer group (RR 1.42, 95% CI 1.26–1.60,P< 0.01) for both women who did experience repeated implantation failure (RIF) (RR 1.58, 95% CI 1.17–2.13,P< 0.01) and did not experience RIF (Non-RIF) (RR 1.44, 95% CI 1.20–1.66,P< 0.01). However, sequential embryo transfer showed no significant benefit over blastocyst embryo transfer.ConclusionThe current systematic review demonstrates that sequential cleavage and blastocyst embryo transfer improve the clinical pregnancy rate over conventional cleavage embryo transfer. For women with adequate embryos, sequential transfer could be attempted following careful consideration. More high-grade evidence from prospective randomized studies is warranted.
Colchicine – an effective treatment for children with a clinical diagnosis of autoinflammatory diseases without pathogenic gene variants
Authors: Welzel Tatjana , Wildermuth Anna L. , Deschner Norbert , Benseler Susanne M. , Kuemmerle-Deschner Jasmin B. 
Published: September 2021

Abstract
Background
Autoinflammatory diseases (AID) are rare chronic conditions with high disease burden, affecting children and adults. Clinically and genetically confirmed, AID can be effectively treated with targeted cytokine inhibition. In contrast, for patients with clinical AID symptoms without pathogenic gene variants, no treatment recommendations are available. Colchicine is approved and established as effective, safe and low-cost first-line therapy in Familial Mediterranean Fever. Up to now, efficacy data for colchicine in children with a clinical AID diagnosis without pathogenic gene variants are rare. This pilot study was performed to evaluate the effectiveness of colchicine in children with a clinical diagnosis of AID without pathogenic gene variants.

Methods
A pilot cohort study of consecutive children with active clinical AID without pathogenic gene variants treated with colchicine monotherapy was performed between 01/2009 and 12/2018. Demographics, clinical and laboratory characteristics were determined serially. Colchicine dosing and safety were documented. Physician estimate of disease activity was captured on visual analogue scales (VAS). Primary outcome: Complete response (PGA ≤2 plus CRP ≤0.5 mg/dL and/or SAA ≤10 mg/L) at last follow-up. Secondary outcomes: partial/no response, flare characteristics and requirement for rescue therapies. Analysis: Nonparametric comparison of disease activity measures.

Results
A total of 33 children were included; 39% were female. Median age at colchicine start was 3.8 years, median follow-up was 14.1 months. Clinical AID diagnoses included CAPS (24%), FMF (27%), PFAPA (43%) and unclassified AID (6%). At baseline, overall disease activity was moderate (PGA 4), inflammatory markers were elevated (CRP 12.1 mg/dL; SAA 289.2 mg/L), and 97% reported febrile flares. Outcome: 55% achieved complete response, 35% showed partial response and 58% had no febrile flares at last follow-up. Inflammatory markers (SAA: p < 0.0001, CRP: p < 0.005) and disease activity (p < 0.0001) decreased significantly. Overall, 93% of children experienced improvement of flare characteristics.

Conclusion
Colchicine was found to be effective and safe in children with a clinical AID diagnosis in the absence of pathogenic gene variants. Colchicine is a low-cost treatment option for non-organ threatening AID.
Attitude theory and measurement in implementation science: a secondary review of empirical studies and opportunities for advancement
Authors: Fishman Jessica , Yang Catherine , Mandell David 
Published: September 2021

Abstract
Background
Implementation science studies often express interest in “attitudes,” a term borrowed from psychology. In psychology, attitude research has an established methodological and theoretical base, which we briefly summarize here. We then review implementation studies designed to measure attitudes and compare their definitions and methods with those from psychology.

Methods
A recent review identified 46 studies empirically examining factors associated with implementation. For each of these studies, we evaluated whether authors included attitudes as a construct of interest, and if so, whether and how the construct was defined, measured, and analyzed.

Results
Most of the articles (29/46 [63%]) mention attitudes as an implementation factor. Six articles include a definition of the construct. Nineteen studies were designed to measure attitudes but lacked clarity in describing how attitudes were measured. Those that explained their measurement approach used methods that differed from one another and from validated methods in social psychology. Few articles described associated analyses or provided results specific to attitudes. Despite the lack of specificity regarding relevant measurement, analysis, and results, the articles often included causal conclusions about the role of attitudes.

Conclusions
Attitudes may be an important construct to implementation scientists, but studies to date are ambiguous in their definitions of attitudes and inconsistent in the methods used to measure and analyze attitudes. We discuss how implementation studies can apply psychology’s standardized definitions, validated measurement approaches, and causal models that include attitudes. This application of attitude theory and methods could offer implementation research valuable scientific opportunities.
A comparison of immediate release and delayed release cysteamine in 17 patients with nephropathic cystinosis
Authors: van Stein Christina , Klank Sabrina , Grüneberg Marianne , Ottolenghi Chris , Grebe Jürgen , Reunert Janine , Harms Erik , Marquardt Thorsten 
Published: September 2021

Abstract
Background
Nephropathic cystinosis is a rare and severe metabolic disease leading to an accumulation of cystine in lysosomes which especially harms kidney function. A lifelong therapy with the aminothiol cysteamine can delay the development of end-stage renal disease and the necessity of kidney transplantation. The purpose of our study was to compare the effectiveness of immediate-release and delayed-release cysteamine on cystine and cysteamine levels as well as assessing the onset of adverse effects.

Methods
We retrospectively analysed cystine and cysteamine levels of 17 patients after a single dose of immediate-release cysteamine (Cystagon®, Mylan Pharmaceuticals, Canonsburg, PA and Recordati Pharma GmbH) as well as a single dose of delayed-release cysteamine (Procysbi®; Horizon Pharma USA and Chiesi Farmaceutici S.p.A., Parma, Italy) respectively. Data were collected during a period of three years in the context of optimizing the individual treatment regimens. The dose of DR-cysteamine was reduced to 70% of the equivalent dose of IR-cysteamine. The efficacy of both formulas in depleting white blood cells’ cystine levels and their side effects were compared.

Results
Immediate (IR)- and delayed-release (DR) cysteamine effectively decreased intracellular cystine levels under the target value of 0.5 nmol cystine/mg protein, while fewer side effects occurred under DR-cysteamine. Mean maximum levels of cysteamine were reached after 60 min with IR-cysteamine and after 180 min with DR-cysteamine.

Conclusion
A therapy with DR-cysteamine is as effective as IR-cysteamine while less side effects were reported. Our data show that DR-cysteamine should be dosed higher than 70% of the equivalent dose of IR-cysteamine in order to decrease cystine levels over an extended period of time. Moreover, our data suggest increasing the dosing scheme of Procysbi® to three times daily, to prevent a rapid decrease and achieve a steadier decline in cystine levels. Due to the more convenient dosing scheme, DR-cysteamine might ameliorate therapy adherence and improve patients’ quality of life.
PRINCESS: comprehensive detection of haplotype resolved SNVs, SVs, and methylation
Authors: Mahmoud Medhat , Doddapaneni Harshavardhan , Timp Winston , Sedlazeck Fritz J. 
Published: September 2021

AbstractLong-read sequencing has been shown to have advantages in structural variation (SV) detection and methylation calling. Many studies focus either on SV, methylation, or phasing of SNV; however, only the combination of variants provides a comprehensive insight into the sample and thus enables novel findings in biology or medicine. PRINCESS is a structured workflow that takes raw sequence reads and generates a fully phased SNV, SV, and methylation call set within a few hours. PRINCESS achieves high accuracy and long phasing even on low coverage datasets and can resolve repetitive, complex medical relevant genes that often escape detection. PRINCESS is publicly available at https://github.com/MeHelmy/princess under the MIT license.
Optimization of Nutrition And Medication (OptiNAM) for acutely admitted older patients: protocol for a randomized single-blinded controlled trial
Authors: Andersen Aino L. , Houlind Morten B. , Nielsen Rikke L. , Jørgensen Lillian M. , Treldal Charlotte , Damgaard Morten , Bengaard Anne Kathrine , Juul-Larsen Helle Gybel , Laursen Louise Bolvig , Iversen Esben , Kruse Marie , Pedersen Anne M. L. , Hornum Mads , Beck Anne M. , Pedersen Mette M. , Ankarfeldt Mikkel Z. , Petersen Janne , Andersen Ove 
Published: September 2021

AbstractBackgroundInternationally, older patients (≥65 years) account for more than 40% of acute admissions. Older patients admitted to the emergency department (ED) are frequently malnourished and exposed to inappropriate medication prescribing, due in part to the inaccuracy of creatinine-based equations for estimated glomerular filtration rate (eGFR). The overall aims of this trial are to investigate: (1) the efficacy of a medication review (MED intervention) independent of nutritional status, (2) the accuracy of eGFR equations based on various biomarkers compared to measured GFR (mGFR) based on99mTechnetium–diethylenetriaminepentaacetic acid plasma clearance, and (3) the efficacy of an individualized multimodal and transitional nutritional intervention (MULTI-NUT-MED intervention) in older patients with or at risk of malnutrition in the ED.MethodsThe trial is a single-center block randomized, controlled, observer-blinded, superiority and explorative trial with two parallel groups. The population consists of 200 older patients admitted to the ED: 70 patients without malnutrition or risk of malnutrition and 130 patients with or at risk of malnutrition defined as a Mini Nutritional Assessment-Short Form score ≤11. All patients without the risk of malnutrition receive the MED intervention, which consists of a medication review by a pharmacist and geriatrician in the ED. Patients with or at risk of malnutrition receive the MULTI-NUT-MED intervention, which consists of the MED intervention in addition to, dietary counseling and individualized interventions based on the results of screening tests for dysphagia, problems with activities of daily living, low muscle strength in the lower extremities, depression, and problems with oral health. Baseline data are collected upon study inclusion, and follow-up data are collected at 8 and 16 weeks after discharge. The primary outcomes are (1) change in medication appropriateness index (MAI) score from baseline to 8 weeks after discharge, (2) accuracy of different eGFR equations compared to mGFR, and (3) change in health-related quality of life (measured with EuroQol-5D-5L) from baseline to 16 weeks after discharge.DiscussionThe trial will provide new information on strategies to optimize the treatment of malnutrition and inappropriate medication prescribing among older patients admitted to the ED.Trail registrationClinicalTrials.govNTC03741283. Retrospectively registered on 14 November 2018.
Advanced-stage Wilms tumor arising in a horseshoe kidney of a 9-year-old child: a case report
Authors: Farouk Abubakar Garba , Ibrahim H. A. , Farate A. , Wabada S. , Mustapha M. G. 
Published: September 2021

Abstract
Background
Horseshoe kidney (HK) is one of the most common renal fusion abnormalities, with an incidence of 1:400 in the normal population. However, Wilms tumor (WT) arising in an HK is a rare occurrence. We report the case of a 9-year-old boy who presented with an advanced WT in an HK and also highlight the management challenges in a resource-poor setting such as ours.

Case presentation
The patient was a 9-year-old Nigerian boy presented to the Pediatrics Outpatient Clinic of the University of Maiduguri Teaching Hospital (UMTH) with a history of progressive abdominal swelling, weight loss, abdominal pain, and cough. Abdominal examination revealed an irregular, firm, and non-tender mass in the right lumbar region. A computed tomography (CT) scan of the abdomen showed a heterogeneously dense mass that was predominantly to the right side of the abdomen and crossed the midline to the left side, where it continued with the relatively normal renal tissue. Chest CT revealed pulmonary metastases. A diagnosis of WT in an HK was made. The patient had a 6-week course of neoadjuvant chemotherapy, and a right nephrectomy and left partial nephrectomy was performed. The final histologic diagnosis of WT was made. Radiotherapy was intended but was not available in our facility, and the parents could not afford referral to another center.

Conclusions
Children with a clinically suspected HK with WT should undergo a careful imaging evaluation such as CT before any surgical intervention. Neoadjuvant chemotherapy to reduce tumor bulk might be a good treatment method to reduce surgical morbidity and aid in complete excision and potential for preserving renal function.
The combination of R2R3-MYB gene AmRosea1 and hairy root culture is a useful tool for rapidly induction and production of anthocyanins in Antirrhinum majus L
Authors: Piao Chunlan , Wu Jinguo , Cui Min-Long 
Published: September 2021

AbstractAnthocyanins are the largest group of water-soluble pigments and beneficial for human health. Although most plants roots have the potential to express natural biosynthesis pathways required to produce specialized metabolites such as anthocyanins, the anthocyanin synthesis is specifically silenced in roots. To explore the molecular mechanism of absence and production ability of anthocyanin in the roots, investigated the effect of a bHLH gene AmDelila, and an R2R3-MYB gene AmRosea1, which are the master regulators of anthocyanin biosynthesis in Antirrhinum majus flowers, by expressing these genes in transformed hairy roots of A. majus. Co-ectopic expression of both AmDelila and AmRosea1 significantly upregulated the expression of the key target structural genes in the anthocyanin biosynthesis pathway. Furthermore, this resulted in strongly enhanced anthocyanin accumulation in transformed hairy roots. Ectopic expression of AmDelila alone did not gives rise to any significant anthocyanin accumulation, however, ectopic expression of AmRosea1 alone clearly upregulated expression of the main structural genes as well as greatly promoted anthocyanin accumulation in transformed hairy roots, where the contents reached 0.773–2.064 mg/g fresh weight. These results suggest that AmRosea1 plays a key role in the regulatory network in controlling the initiation of anthocyanin biosynthesis in roots, and the combination of AmRosea1 and hairy root culture is a powerful tool to study and production of anthocyanins in the roots of A. majus.
Discrete-time phytoplankton–zooplankton model with bifurcations and chaos
Authors: Khan A. Q. , Javaid M. B. 
Published: September 2021

AbstractThe local dynamics with different topological classifications, bifurcation analysis, and chaos control for the phytoplankton–zooplankton model, which is a discrete analogue of the continuous-time model by a forward Euler scheme, are investigated. It is proved that the discrete-time phytoplankton–zooplankton model has trivial and semitrivial fixed points for all involved parameters, but it has an interior fixed point under the definite parametric condition. Then, by linear stability theory, local dynamics with different topological classifications are investigated around trivial, semitrivial, and interior fixed points. Further, for the discrete-time phytoplankton–zooplankton model, the existence of periodic points is also investigated. The existence of possible bifurcations around trivial, semitrivial, and interior fixed points is also investigated, and it is proved that there exists a transcritical bifurcation around a trivial fixed point. It is also proved that around trivial and semitrivial fixed points of the phytoplankton–zooplankton model there exists no flip bifurcation, but around an interior fixed point there exist both Neimark–Sacker and flip bifurcations. From the viewpoint of biology, the occurrence of Neimark–Sacker implies that there exist periodic or quasi-periodic oscillations between phytoplankton and zooplankton populations. Next, the feedback control method is utilized to stabilize chaos existing in the phytoplankton–zooplankton model. Finally, simulations are presented to validate not only obtained results but also the complex dynamics with orbits of period-8, 9, 10, 11, 14, 15 and chaotic behavior of the discrete-time phytoplankton–zooplankton model.
The LRA Workbench: an IDE for efficient REST API composition through linked metadata
Authors: Serrano Diego , Stroulia Eleni 
Published: September 2021

AbstractThe number of Web APIs for accessing information and services is continuously increasing, and yet, no tools exist to automate the time-consuming and error-prone process of invoking those APIs and composing their responses. The recent emergence of widely-adopted, standardized, Web-API description formats and the development of Linked Data technologies for data integration have motivated our work on the LRA (Linked REST APIs) methodology [1, 2]. LRA relies on RDF service specifications to automate the development process around the usage of Web APIs. This automation represents a great opportunity to systematize and improve the quality of service-oriented application development. However, LRA’s reliance on SPARQL as the user-interaction model may hinder its adoption, because it requires developers to learn the intricacies of the unconventional graph data model and its associated datasets. In this paper we have developed the LRA Workbench ($$LRA_{Wbench}$$LRAWbench), which takes advantage of the emergent schema of Web-API specifications, in order to simplify the formulation of LRA-compliant SPARQL queries. Our empirical evaluation of the$$LRA_{Wbench}$$LRAWbench usability demonstrates that our tool significantly improves the performance of developers formulating SPARQL queries for LRA. A subsequent study on the effectiveness of the$$LRA_{Wbench}$$LRAWbench demonstrated that developers using LRA tend to produce code with considerable better structural complexity, in less time, than developers manually composing APIs.