bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infectious Risk Mitigation in Patients with Multiple Sclerosis under Disease-Modifying Therapies – the Experience of a Collaborative Neurology-Infectious Diseases Approach
Authors: Ferro Daniela , Prista-Leão Beatriz , Costa Andreia , Silva-Pinto André , Abreu Cândida , Sá Maria José 
Published: September 2021

Background Multiple sclerosis treatment has changed in the last years with the emergence of new disease-modifying therapies (DMTs). Despite a better efficacy profile, these drugs raise concerns about infectious risk, which needs to be mitigated. Objective To analyze the results of a systematic collaborative approach between Neurology and Infectious Diseases (ID) Departments in the management of infectious risk and complications in MS patients treated with DMT. Methods Retrospective collection of MS patients’ demographic and clinical data from clinical records of MS and ID outpatient clinics (2011–2017). Results We included 149 patients: most had evidence of previous contact with Herpesviridae, and half of them were not immune to hepatitis A and B viruses (HAV and HBV). Vaccines for HAV, HBV, and Streptococcus pneumoniae were administered in 91%, 78%, and 88% of non-immune patients, respectively. JC virus serology monitoring prevented natalizumab (NTZ) initiation or prompted its switch in 34/122 patients. Forty patients had latent tuberculosis, in which 88% were treated. Infectious events occurred in 33 patients, mostly mild urinary, respiratory, and herpes virus group infections. Only three patients required inpatient care. Conclusion Facing the expansion of the new DMT, we highlight the benefits of an interdisciplinary approach for safer use of the chosen treatment.
A Review Exploring Acculturation and Type 2 Diabetes in Spanish-Speaking Populations
Authors: Miller De Rutté Alyssia M. , Barrie Amanda 
Published: September 2021

Background: Acculturation to the United States has been previously studied in Spanish-speaking populations, but little is known about the potential relationship between acculturation and type 2 diabetes mellitus (T2DM). Objective: The purpose of this review was to explore the relationship between acculturation and T2DM in Spanish-speaking populations in the United States. Methods: Selected studies collected from a review of literature were analyzed by population, ethnicity, acculturation scale, and significance. Results: Thirty-two eligible articles showed conflicting data between the effects of acculturation on T2DM. Conclusion: Overall, studies yielded inconclusive results on the significance of the relationship between acculturation and diabetes in Spanish-speaking populations, which merit further investigation.
Stress urinary incontinence in females. Diagnosis and treatment modalities – past, present and the future
Authors: Anand Ajay , Khan Suhail Masood , Khan Azhar Ajaz 
Published: September 2021

Introduction: Stress urinary incontinence (SUI) can be defined as involuntary and unintentional loss of urine through the urethra when vesical pressure exceeds the urethral sphincter pressure during instances of coughing, sneezing or physical exercise. Stress urinary incontinence is the most common form of incontinence in females with an estimated prevalence of 4.5–53% in adult women with urinary incontinence. Yet despite its distressing nature and a negative impact on quality of life, very few women present with their symptoms to a urologist. Materials and methods: A literature search of the MEDLINE, Cochrane Library, Embase, NLH, ClinicalTrials.gov and Google Scholar databases was done up to November 2020, using terms related to SUI, medical therapy, surgical therapy and treatment options. The search terms included female stress urinary incontinence, mid-urethral sling, tension-free vaginal tape and trans obturator tape. The search included original articles, reviews and meta-analyses. Conclusion: Current guidelines for the management of stress urinary incontinence propose a step-ladder pattern, based on treatment invasiveness starting from conservative therapies, then drugs followed by minimally invasive procedures and culminating in invasive surgeries. The surgical approach is to be considered only after conservative therapies fail. The recent advances in the treatment of stress urinary incontinence have brought to light newer modalities and newer technologies that can be utilized which include laser therapy, stem cell therapy, intravesical balloon and others that show a lot of promise. This paper provides an in-depth analysis and reviews the literature on the current modalities and the future prospects of female stress urinary incontinence. Level of evidence: Not applicable for this review article.
Effect of Antioxidant and Buffering Agent Mixture on Dentin Shear Bond Strengths of Laminate Veneer and pH Change of External Medium After Intracoronal Bleaching
Authors: Kurklu Zeliha Gonca Bek 
Published: September 2021

Aim: To investigate the effect of sodium ascorbate (SA), an antioxidant and calcium hydroxide (Ca(OH)2), a buffering agent mixture, on the shear bond strength of a luting resin to dentin, and pH changes of the extraradicular medium solution after intracoronal bleaching with hydrogen peroxide. Materials and Methods: In this in vitro study, 60 human maxillary central incisors were randomly assigned into six groups ( n: 10): Group 1: restored, no bleach; group 2: bleached, bonded immediately; group 3: bleached, treated with 10% SA applications before bonding; group 4: bleached, treated with calcium hydroxide applications before bonding; group 5: bleached, treated with CaOH2 and SA mixture applications before bonding; group 6: delay bonding by seven days. For bleach treatment in groups 2 to 6, intracoronal bleaching was performed with 35% hydrogen peroxide for four days. SA or CaOH2 or mixture of SA and CaOH2 were left in the access cavity for four days. Hybrid blocks, 4 mm × 4 mm wide × 2–mm thick, were luted with resin cements on dentin surface and then the specimens were subjected to shear bond strength testing. Analysis of variance and Tukey post hoc multiple comparison tests were applied ( P < .05). Results: G2 and G4 showed significantly low bond strength values and they were lower than the other groups ( P < .05). There were no significant differences between G1, G3, and G6 ( P > .05). The pH values had risen markedly in the groups containing calcium hydroxide (G4 and G5) after four days ( P < .05). Conclusion: The application of 10% SA or 10% SA and CaOH2 mixture were effective at reversing bleaching effects on bond strength. CaOH2 or CaOH2 and 10% SA mixture increased the external medium pH and were effective for alkalinization after intracoronal bleaching.
Pembrolizumab for B-cell lymphomas relapsing after or refractory to CD19-directed CAR T-cell therapy
Authors: Chong Elise A. , Alanio Cécile , Svoboda Jakub , Nasta Sunita D. , Landsburg Daniel J. , Lacey Simon F. , Ruella Marco , Bhattacharyya Siddharth , Wherry E. John , Schuster Stephen J. 
Published: September 2021

AbstractCD19-directed chimeric antigen receptor–modified (CAR T) T cells achieve durable remissions in about 30% to 40% of relapsed/refractory large B-cell lymphomas. T-cell exhaustion and/or an immunosuppressive tumor microenvironment may contribute to CAR T-cell failure. Pembrolizumab, an anti-PD1 immune checkpoint inhibitor, may reverse T-cell exhaustion after CAR T-cell therapy. We treated 12 patients with B-cell lymphomas who were either refractory to (n = 9) or relapsed after (n = 3) CD19-directed CAR T-cell (4-1BB–costimulated) therapy with pembrolizumab 200 mg IV every 3 weeks. Median time from CAR T-cell infusion to first pembrolizumab dose was 3.3 months (range, 0.4-42.8 months). Pembrolizumab was well tolerated, and the only grade ≥3 adverse events related to pembrolizumab were neutropenia (n = 3; 25%). Best overall response rate after pembrolizumab was 25% (3 of 12 patients; 1 complete response; 2 partial responses). One (8%) patient had stable disease; thus, 4 of 12 (33%) patients had clinical benefit. After pembrolizumab, 4 patients with clinical benefit had an increase in percentage of CAR T cells by mass cytometry by time of flight (CyTOF); 3 of 4 of these patients also had increases in CAR19 transgene levels by quantitative polymerase chain reaction. Deep immune profiling using CyTOF revealed increased CAR T-cell activation and proliferation and less T-cell exhaustion in clinical responders. Together, PD1 blockade with pembrolizumab after CD19-directed CAR T-cell therapy appears safe and may achieve clinical responses in some patients with B-cell lymphomas refractory to or relapsed after CAR T-cell therapy. This trial was registered at www.clinicaltrials.gove as #NCT02650999.
Population pharmacokinetic modeling of factor concentrates in hemophilia: an overview and evaluation of best practice
Authors: Goedhart Tine M. H. J. , Bukkems Laura H. , Zwaan C. Michel , Mathôt Ron A. A. , Cnossen Marjon H. ,   for the OPTI-CLOT study group and SYMPHONY consortium
Published: September 2021

Abstract
The accuracy of pharmacokinetic (PK)-guided dosing depends on the clinical and laboratory data used to construct a population PK model, as well as the patient’s individual PK profile. This review provides a detailed overview of data used for published population PK models for factor VIII (FVIII) and factor IX (FIX) concentrates, to support physicians in their choices of which model best suits each patient. Furthermore, to enhance detailed data collection and documentation, we do suggestions for best practice. A literature search was performed; publications describing prophylactic population PK models for FVIII and FIX concentrates based on original patient data and constructed using nonlinear mixed-effect modeling were included. The following data were collected: detailed demographics, type of product, assessed and included covariates, laboratory specifications, and validation of models. Included models were scored according to our recommendations for best practice, specifically scoring the quality of data documentation as reported. Respectively, 20 models for FVIII and 7 for FIX concentrates were retrieved. Although most models (22/27) included pediatric patients, only 4 reported detailed demographics. The wide range of body weights suggested that overweight and obese adults were represented. Twenty-six models reported the assay applied to measure factor levels, whereas only 16 models named reagents used. Eight models were internally validated using a data subset. This overview presents detailed information on clinical and laboratory data used for published population PK models. We provide recommendations on data collection and documentation to increase the reliability of PK-guided prophylactic dosing of factor concentrates in hemophilia A and B.
Tumor-associated antigen–specific T cells with nivolumab are safe and persist in vivo in relapsed/refractory Hodgkin lymphoma
Authors: Dave Hema , Terpilowski Madeline , Mai Mimi , Toner Keri , Grant Melanie , Stanojevic Maja , Lazarski Christopher , Shibli Abeer , Bien Stephanie A. , Maglo Philip , Hoq Fahmida , Schore Reuven , Glenn Martha , Hu Boyu , Hanley Patrick J. , Ambinder Richard , Bollard Catherine M. 
Published: September 2021

Abstract
Hodgkin lymphoma (HL) Reed Sternberg cells express tumor-associated antigens (TAA) that are potential targets for cellular therapies. We recently demonstrated that TAA-specific T cells (TAA-Ts) targeting WT1, PRAME, and Survivin were safe and associated with prolonged time to progression in solid tumors. Hence, we evaluated whether TAA-Ts when given alone or with nivolumab were safe and could elicit antitumor effects in vivo in patients with relapsed/refractory (r/r) HL. Ten patients were infused with TAA-Ts (8 autologous and 2 allogeneic) for active HL (n = 8) or as adjuvant therapy after hematopoietic stem cell transplant (n = 2). Six patients received nivolumab priming before TAA-Ts and continued until disease progression or unacceptable toxicity. All 10 products recognized 1 or more TAAs and were polyfunctional. Patients were monitored for safety for 6 weeks after the TAA-Ts and for response until disease progression. The infusions were safe with no clear dose-limiting toxicities. Patients receiving TAA-Ts as adjuvant therapy remain in continued remission at 3+ years. Of the 8 patients with active disease, 1 patient had a complete response and 7 had stable disease at 3 months, 3 of whom remain with stable disease at 1 year. Antigen spreading and long-term persistence of TAA-Ts in vivo were observed in responding patients. Nivolumab priming impacted TAA-T recognition and persistence. In conclusion, treatment of patients with r/r HL with TAA-Ts alone or in combination with nivolumab was safe and produced promising results. This trial was registered at www.clinicaltrials.gov as #NCT022039303 and #NCT03843294.
An mRNA assay system demonstrates proteasomal-specific degradation contributes to cardiomyopathic phospholamban null mutation
Authors: Rohner Eduarde , Witman Nevin , Sohlmer Jesper , De Genst Erwin , Louch William E. , Sahara Makoto , Chien Kenneth R. 
Published: September 2021

AbstractBackgroundThe human L39X phospholamban (PLN) cardiomyopathic mutant has previously been reported as a null mutation but the detailed molecular pathways that lead to the complete lack of detectable protein remain to be clarified. Previous studies have shown the implication between an impaired cellular degradation homeostasis and cardiomyopathy development. Therefore, uncovering the underlying mechanism responsible for the lack of PLN protein has important implications in understanding the patient pathology, chronic human calcium dysregulation and aid the development of potential therapeutics.MethodsA panel of mutant and wild-type reporter tagged PLN modified mRNA (modRNA) constructs were transfected in human embryonic stem cell-derived cardiomyocytes. Lysosomal and proteasomal chemical inhibitors were used together with cell imaging and protein analysis tools in order to dissect degradation pathways associated with expressed PLN constructs. Transcriptional profiling of the cardiomyocytes transfected by wild-type or L39X mutant PLN modRNA was analysed with bulk RNA sequencing.ResultsOur modRNA assay system revealed that transfected L39X mRNA was stable and actively translated in vitro but with only trace amount of protein detectable. Proteasomal inhibition of cardiomyocytes transfected with L39X mutant PLN modRNA showed a fourfold increase in protein expression levels. Additionally, RNA sequencing analysis of protein degradational pathways showed a significant distinct transcriptomic signature between wild-type and L39X mutant PLN modRNA transfected cardiomyocytes.ConclusionOur results demonstrate that the cardiomyopathic PLN null mutant L39X is rapidly, actively and specifically degraded by proteasomal pathways. Herein, and to the best of our knowledge, we report for the first time the usage of modified mRNAs to screen for and illuminate alternative molecular pathways found in genes associated with inherited cardiomyopathies.
Patency period of a metallic ureteral stent and its determinants in patients with malignant ureteral obstruction: a prospective review
Authors: Kobayashi Yasuyuki , Arai Hiroki , Honda Masahito 
Published: September 2021

Abstract
Background
Malignant ureteral obstruction caused by extrinsic compression of a primary malignant tumour or by metastatic disease is an indicator of poor prognosis with a median life expectancy of about one year. We examined clinical outcomes following Resonance Metallic Ureteral Stent (Cook Medical, Bloomington, IN) placement in patients with malignant ureteral obstruction.

Methods
This was a prospective study of patients with malignant ureteral obstruction who underwent Resonance Metallic Ureteral Stent placement from April 2016 to March 2021. We registered 21 patients (27 collecting systems) with malignant ureteral obstruction and observed them prospectively. The patients first underwent polymer ureteral stent placement followed by replacement with a metallic ureteral stent one month later. Primary outcome was the metallic ureteral stent patency period based on both serum creatinine and the level of hydronephrosis; secondary outcomes were factors affecting patency period and stent-related complications such as symptoms of obstruction (flank pain), bladder irritation, haematuria, and urinary tract infection (presence or absence of fever).

Results
The study comprised 21 patients (six men, 15 women) with a mean age of 72 years. The median stent patency period in days was not available (NA) (95% CI 210–NA) due to the inability to extract this value from the Kaplan–Meier curve because the event rate did not reach 50%, and the one-year patency rate was 59.2% (95% CI 23.2–82.9). A normal serum creatinine (0.65 to 1.07 mg/dL for men and 0.46 to 0.79 mg/dL for women) one week after polymer ureteral stent placement was a significant factor affecting the long-term metallic ureteral stent patency period. There were no major complications.

Conclusion
The Resonance Metallic Ureteral Stent was effective and safe for patients with malignant ureteral obstruction. A normal serum creatinine level one week after placement of a polymer ureteral stent may predict a longer patency period of metallic ureteral stents in patients with malignant ureteral obstruction.
A simulation study of a honeybee breeding scheme accounting for polyandry, direct and maternal effects on colony performance
Authors: Kistler Tristan , Basso Benjamin , Phocas Florence 
Published: September 2021

Abstract
Background
Efficient breeding programs are difficult to implement in honeybees due to their biological specificities (polyandry and haplo-diploidy) and complexity of the traits of interest, with performances being measured at the colony scale and resulting from the joint effects of tens of thousands of workers (called direct effects) and of the queen (called maternal effects). We implemented a Monte Carlo simulation program of a breeding plan designed specifically for Apis mellifera’s populations to assess the impact of polyandry versus monoandry on colony performance, inbreeding level and genetic gain depending on the individual selection strategy considered, i.e. complete mass selection or within-family (maternal lines) selection. We simulated several scenarios with different parameter setups by varying initial genetic variances and correlations between direct and maternal effects, the selection strategy and the polyandry level. Selection was performed on colony phenotypes.

Results
All scenarios showed strong increases in direct breeding values of queens after 20 years of selection. Monoandry led to significantly higher direct than maternal genetic gains, especially when a negative correlation between direct and maternal effects was simulated. However, the relative increase in these genetic gains depended also on their initial genetic variability and on the selection strategy. When polyandry was simulated, the results were very similar with either 8 or 16 drones mated to each queen. Across scenarios, polyandrous mating resulted in equivalent or higher gains in performance than monoandrous mating, but with considerably lower inbreeding rates. Mass selection conferred a ~ 20% increase in performance compared to within-family selection, but was also accompanied by a strong increase in inbreeding levels (25 to 50% higher).

Conclusions
Our study is the first to compare the long-term effects of polyandrous versus monoandrous mating in honeybee breeding. The latter is an emergent strategy to improve specific traits, such as resistance to varroa, which can be difficult or expensive to phenotype. However, if used during several generations in a closed population, monoandrous mating increases the inbreeding level of queens much more than polyandrous mating, which is a strong limitation of this strategy.
A novel automated image analysis pipeline for quantifying morphological changes to the endoplasmic reticulum in cultured human cells
Authors: Garcia-Pardo M. Elena , Simpson Jeremy C. , O’Sullivan Niamh C. 
Published: September 2021

AbstractBackgroundIn mammalian cells the endoplasmic reticulum (ER) comprises a highly complex reticular morphology that is spread throughout the cytoplasm. This organelle is of particular interest to biologists, as its dysfunction is associated with numerous diseases, which often manifest themselves as changes to the structure and organisation of the reticular network. Due to its complex morphology, image analysis methods to quantitatively describe this organelle, and importantly any changes to it, are lacking.ResultsIn this work we detail a methodological approach that utilises automated high-content screening microscopy to capture images of cells fluorescently-labelled for various ER markers, followed by their quantitative analysis. We propose that two key metrics, namely the area of dense ER and the area of polygonal regions in between the reticular elements, together provide a basis for measuring the quantities of rough and smooth ER, respectively. We demonstrate that a number of different pharmacological perturbations to the ER can be quantitatively measured and compared in our automated image analysis pipeline. Furthermore, we show that this method can be implemented in both commercial and open-access image analysis software with comparable results.ConclusionsWe propose that this method has the potential to be applied in the context of large-scale genetic and chemical perturbations to assess the organisation of the ER in adherent cell cultures.
Identification of reference genes for gene expression studies among different developmental stages of murine hearts
Authors: Ren Jie , Zhang Ningning , Li Xiangjie , Sun Xiaogang , Song Jiangping 
Published: September 2021

Abstract
Background
Real-time quantitative polymerase chain reaction (RT-qPCR) is a widely-used standard assay for assessing gene expression. RT-qPCR data requires reference genes for normalization to make the results comparable. Therefore, the selected reference gene should be highly stable in its expression throughout the experimental datasets. So far, reports about the optimal set of reference genes in murine left ventricle (LV) across embryonic and postnatal stages are few. The objective of our research was to identify the appropriate reference genes in murine LV among different developmental stages.

Methods
We investigated the gene expression profiles of 21 widely used housekeeping genes in murine LV from 7 different developmental stages (almost throughout the whole period of the mouse lifespan). The stabilities of the potential reference genes were evaluated by five methods: GeNorm, NormFinder, BestKeeper, Delta-Ct and RefFinder.

Results
We proposed a set of reliable reference genes for normalization of RT-qPCR experimental data in different conditions. Furthermore, our results showed that 6 genes (18S, Hmbs, Ubc, Psmb4, Tfrc and Actb) are not recommended to be used as reference genes in murine LV development studies. The data also suggested that the Rplp0 gene might serve as an optimal reference gene in gene expression analysis.

Conclusions
Our study investigated the expression stability of the commonly used reference genes in process of LV development and maturation. We proposed a set of optimal reference genes that are suitable for accurate normalization of RT-qPCR data in specific conditions. Our findings may be helpful in future studies for investigating the gene expression patterns and mechanism of mammalian heart development.