bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between Low to Moderate Consumption of Alcoholic Beverage Types and Health Outcomes: A Systematic Review
Authors: Estruch Ramon , Hendriks Henk F J 
Published: November 2021

Abstract

Aims
There is limited research comparing light to moderate wine, beer and spirits consumption and their impact on long-term health. This systematic review aims to investigate the studies published in the past 10 years and qualitatively assess the similarities and differences between the three main beverages, when consumed at a low to moderate level, for their associations with various health outcomes.

Methods
A systematic search was conducted for comparative studies published in English language (2010 to mid-2021) of beverage-specific low to moderate alcohol consumption associated with all-cause mortality, cancer, cardiovascular disease and diabetes mellitus type II.

Results
The search yielded a total of 24 studies (8 meta-analyses; 15 prospective studies and 1 pooled analysis). Overall, most studies showed similar associations of different alcoholic beverages with chronic conditions, including all-cause mortality, many types of cancer, cardiovascular disease and diabetes mellitus type II. Not all data are consistent. Some studies show more beneficial or detrimental effects of wine than other beverage types, whereas other studies show such effects for other beverages.

Conclusion
Moderate consumption of one specific alcoholic beverage (wine, beer or spirits) may not be consistently associated with higher or lower risks for common health outcomes as compared with moderate consumption of any of the other alcoholic beverages.
Development and Validation of Reversed-Phase HPLC Method for the Determination of Epirubicin and Its Application to the Pharmacokinetic Study of Epirubicin Loaded Polymeric Nanoparticle Formulations in Rats
Authors: Khalil Saifullah Khan , Iqbal Zafar , Niaz Nabeela , Iftikhar Tayyaba 
Published: November 2021

AbstractEpirubicin, commonly used as anticancer drug for various types of tumors like breast, liver, lung, stomach, ovaries, and bladder for its improved antitumor efficacy and safety. A rapid, sensitive, and reliable bioanalytical method was developed and validated for epirubicin using conventional reverse phase HPLC with UV detection. The developed method was successfully applied to investigate the pharmacokinetics of epirubicin after intravenous administration of a reference epirubicin and its designed nano-formulations to rats. C18 column was used in an isocratic mode for analyte elution at a flow rate of 1.0 mL/min with UV detection of 234 nm. The mobile phase was composed of acetonitrile 22% (channel A) and 0.025% tri fluoro-acetic acid in water (channel B). Ondansetron was added as an internal standard, and the plasma samples were analyzed after protein precipitation. A concentration range of 0.016–1.024 μg/mL was selected for the construction of calibration curves, with LLOQ of 0.016 μg/mL. Results showed that the value of AUC, half-life, and mean residence time of designed nano-formulation were bounce to 10, 9, and 11 times higher, when compared to the reference epirubicin after intravenous dose of 10 mg/kg of epirubicin to rats, respectively. The designed epirubicin nano-formulations achieved clinically significant pharmacokinetic values in rats. Current method will help epirubicin future research using clinical samples and drug bioequivalence studies on various novel formulations for drug safety purposes.
Primary hyperoxaluria: the pediatric nephrologist's point of view
Authors: Ben-Shalom Efrat , Garrelfs Sander F , Groothoff Jaap W 
Published: November 2021

ABSTRACT
The clinical presentation of primary hyperoxaluria in children ranges from mildly symptomatic nephrocalcinosis to very early onset end-stage kidney failure with systemic oxalosis, a devastating complication. We review the various manifestations of pediatric hyperoxaluria, treatment options for children with preserved kidney function and appropriate dialysis regimens. Liver or combined liver/kidney transplantation is currently the only definitive treatment for primary hyperoxaluria type 1, but novel RNA interference treatments offer hope for the future. Finally, we address the medical and ethical dilemmas facing pediatricians treating children with hyperoxaluria.
Differential Serum-intestinal Dynamics of Infliximab and Adalimumab in Inflammatory Bowel Disease Patients
Authors: Bar-Yoseph Haggai , Blatt Alexandra , Gerassy Shiran , Pressman Sigal , Mousa Amjad , Sabo Edmond , Waterman Matti , Ungar Bella , Ben-Horin Shomron , Chowers Yehuda 
Published: November 2021

Abstract

Background and Aims
Therapeutic drug monitoring is used to guide anti-tumour necrosis factor [TNF] therapy. However, the associations between serum drug levels [SDL], TNF-bound, and free anti-TNF in the target tissue are incompletely defined. We aimed to assess the interactions between these parameters in inflammatory bowel disease [IBD] patients.

Methods: Enzyme-linked immunosorbent
assays [ELISA assays] were used to detect free drug and TNF-drug complexes in intestinal tissues. Concurrent SDL, anti-drug antibodies [ADA], pharmacotherapy, clinical response, endoscopic appearance, and histological severity were determined. Comparisons between anti-TNFs and paired inflamed/non-inflamed tissue were performed. Variables were correlated and potential interactions detected using multivariate analysis.

Results
A total of 95 biopsies taken from 49 anti-TNF treated IBD patients [26 receiving infliximab and 23 adalimumab] were studied. Free drug levels were higher in inflamed compared with non-inflamed paired specimens. Tissue free-drug and TNF-drug complexes levels were higher in adalimumab-treated patients. In adalimumab-treated patients, SDL were correlated with free drug, but not TNF-drug complex levels, in both inflamed and non-inflamed segments. In infliximab-treated patients, higher SDL were associated with the presence of tissue free drug in both inflamed and non-inflamed segments, whereas TNF-drug complexes were mostly detected in non-inflamed but not in inflamed tissue. In the presence of ADA, neither free drug nor TNF-infliximab complexes were measured in the tissue. Tissue levels did not correlate well with clinical, endoscopic, or histological scores.

Conclusions
SDL correlated with tissue free drug levels; however, different dynamics were observed for TNF-drug complex levels. Infliximab and adalimumab tissue drug dynamics differ. Better understanding of these interactions may allow future therapeutic optimisation.
Genome-Scale Data Reveal Deep Lineage Divergence and a Complex Demographic History in the Texas Horned Lizard (Phrynosoma cornutum) throughout the Southwestern and Central United States
Authors: Finger Nicholas , Farleigh Keaka , Bracken Jason T , Leaché Adam D , François Olivier , Yang Ziheng , Flouri Tomas , Charran Tristan , Jezkova Tereza , Williams Dean A , Blair Christopher 
Published: November 2021

AbstractThe southwestern and central United States serve as an ideal region to test alternative hypotheses regarding biotic diversification. Genomic data can now be combined with sophisticated computational models to quantify the impacts of paleoclimate change, geographic features, and habitat heterogeneity on spatial patterns of genetic diversity. In this study, we combine thousands of genotyping-by-sequencing (GBS) loci with mtDNA sequences (ND1) from the Texas horned lizard (Phrynosoma cornutum) to quantify relative support for different catalysts of diversification. Phylogenetic and clustering analyses of the GBS data indicate support for at least three primary populations. The spatial distribution of populations appears concordant with habitat type, with desert populations in AZ and NM showing the largest genetic divergence from the remaining populations. The mtDNA data also support a divergent desert population, but other relationships differ and suggest mtDNA introgression. Genotype–environment association with bioclimatic variables supports divergence along precipitation gradients more than along temperature gradients. Demographic analyses support a complex history, with introgression and gene flow playing an important role during diversification. Bayesian multispecies coalescent analyses with introgression (MSci) analyses also suggest that gene flow occurred between populations. Paleo-species distribution models support two southern refugia that geographically correspond to contemporary lineages. We find that divergence times are underestimated and population sizes are overestimated when introgression occurred and is ignored in coalescent analyses, and furthermore, inference of ancient introgression events and demographic history is sensitive to inclusion of a single recently admixed sample. Our analyses cannot refute the riverine barrier or glacial refugia hypotheses. Results also suggest that populations are continuing to diverge along habitat gradients. Finally, the strong evidence of admixture, gene flow, and mtDNA introgression among populations suggests that P. cornutum should be considered a single widespread species under the General Lineage Species Concept.
Balancing Animal Welfare, Human Safety, and Research in Agriculture High Containment
Authors: Pickering Brad , Lewis Charles E 
Published: November 2021

Abstract
Livestock research is paramount to understanding the risks associated with unintentional and intentional introductions of emerging, reemerging, and transboundary animal diseases, including their relationship to both the security of the economy and the nation’s food supply. Research involving large animal species conducted in maximum containment Biosafety Level (BSL)-3Ag and BSL-4 facilities include Health and Human Services and United States Department of Agriculture Select Agents that can have severe consequences on both animal agricultural industry and public health. This themed issue of ILAR spans the spectrum of concerns related to this special niche within the animal research community with an emphasis on a review of available research, current trends, and novel approaches relevant to those conducting large animal research with high-risk agents and those charged with regulating those facilities and programs. Articles are authored by those embedded in the high- and maximum-containment community, directly involved with the work, detailing the unique challenges associated with BSL-3 and BSL-4 livestock research.
Impact of rapid susceptibility testing on antimicrobial therapy and clinical outcomes in Gram-negative bloodstream infections
Authors: Anton-Vazquez Vanesa , Suarez Cristina , Planche Timothy 
Published: November 2021

Abstract

Background
Rapid antimicrobial susceptibility testing (rAST) has the potential to improve care of bloodstream infections.

Objectives
The aim of this service evaluation was to assess the impact of rAST on antimicrobial therapy and clinical outcomes in patients with Gram-negative bloodstream infection.

Methods
A prospective service evaluation was conducted from March 2018 to December 2018. A rAST system (Alfred 60AST) was run Monday–Friday before midday and results were communicated to clinicians on the same day as positive blood culture, with subsequent conventional AST performed. Times to antibiotic therapy and clinical outcomes were compared between rAST and conventional AST.

Results
One hundred and ninety-one patients with Gram-negative bacteraemia were included (93 in the rapid group and 98 in the conventional group). Aminoglycoside combination therapy was stopped earlier in the rapid group [32 h (0–795) versus 54 h (4–216), P = 0.002]. The median time to optimal antibiotic based on AST results was significantly shorter than that in the conventional group [50 h (10–339) versus 69.5 h (20–872), P = 0.034]. In the subgroup of patients on ineffective empirical antibiotic, time to effective antibiotic was shorter in the rapid group [39.5 h (32–97) versus 57 h (49–83), P = 0.036]. No differences were found in 28 day mortality or length of stay.

Conclusions
Rapid susceptibility testing resulted in faster discontinuation of aminoglycosides and a shorter time to starting effective and optimal antibiotic when compared with conventional AST results. rAST has potential clinical benefits and points to the need for larger future studies in areas of high antibiotic resistance.
Scirtothrips dorsalis (Thysanoptera: Thripidae) Is a Pest of Celery, Apium graveolens (Apiales: Apiaceae): First Report and Diagnostic Characters
Authors: Sreerama Kumar Prakya , Remani Rachana Rajan 
Published: November 2021

Abstract
Scirtothrips dorsalis (Hood), the chilli thrips, is reported for the first time as a pest of celery, Apium graveolens L. Infested celery plants in a polyhouse at Kalahalli village (13°05′46.0′′N, 77°47′12.2′′E) in Hoskote taluk of Bengaluru Rural district, Karnataka, India, had light to dark brownish scars on various parts besides discolored and distorted leaves. Association of fungal or bacterial disease was dismissed based on microscopic analysis of tissue sections. Eggs, juveniles, and adults of thrips were abundant, especially on the leaves. Diagnostic characters of the adult S. dorsalis collected on celery are presented here along with photomicrographs. Juvenile and adult stages of S. dorsalis were also recorded on 27 other plant species in 18 families during the surveys conducted in 18 districts of Karnataka from 2015 to 2021. The possible role of S. dorsalis as a vector of tospoviruses in celery needs to be investigated.
Recent progress and future perspective of electron cryomicroscopy for structural life sciences
Authors: Namba Keiichi , Makino Fumiaki 
Published: November 2021

AbstractThe three-dimensional structure of biological macromolecules, such as proteins and nucleic acids, and their complexes is the fundamental information not only for life sciences but also for medical sciences and drug design. Electron cryomicroscopy has become an extremely powerful tool for high-resolution structural analysis of biological macromolecules, not just in addition to X-ray crystallography and nuclear magnetic resonance sepectroscopy (NMR) that have been used as the basic techniques in structural biology. By the development of hardware and software, such as transmission electron cryomicroscopes with highly stable and controllable electron optics, cold field emission gun and energy filter, complementary metal oxide semiconductor (CMOS)-based direct electron detectors with high frame rate and high sensitivity, high-speed computers and software programs for image analysis, electron cryomicroscopy now allows structure determination of biological macromolecules at atomic levels within a few days even from a drop of solution sample with an amount as small as a few micrograms. How can the structures of macromolecules be imaged and analyzed at atomic level resolution in their native states despite their high sensitivity to radiation damage at a relatively low level of electron irradiation? We describe recent progress and future perspective of electron cryomicroscopy for structural life sciences.
S1417CD: A Prospective Multicenter Cooperative Group-Led Study of Financial Hardship in Metastatic Colorectal Cancer Patients
Authors: Shankaran Veena , Unger Joseph M , Darke Amy K , Suga Jennifer Marie , Wade James L , Kourlas Peter J , Chandana Sreenivasa R , O’Rourke Mark A , Satti Suma , Liggett Diane , Hershman Dawn L , Ramsey Scott D 
Published: November 2021

Abstract

Background
Financial toxicity is a growing problem in oncology, but no prior studies have prospectively measured the financial impact of cancer treatment in a diverse national cohort of newly diagnosed cancer patients. S1417CD was the first cooperative group-led multicenter prospective cohort study to evaluate financial hardship in metastatic colorectal cancer (mCRC) patients.

Methods
Patients aged 18 years or older within 120 days of mCRC diagnosis completed quarterly questionnaires for 12 months. We estimated the cumulative incidence of major financial hardship (MFH), defined as 1 or more of increased debt, new loans from family and/or friends, selling or refinancing home, or 20% or more income decline. We evaluated the association between patient characteristics and MFH using multivariate cox regression and the association between MFH and quality of life using linear regression.

Results
A total of 380 patients (median age = 59.9 years) were enrolled; 77.7% were White, 98.0% insured, and 56.5% had annual income of $50 000 or less. Cumulative incidence of MFH at 12 months was 71.3% (95% confidence interval = 65.7% to 76.1%). Age, race, marital status, and income (split at $50 000 per year) were not statistically significantly associated with MFH. However, income less than $100 000 and total assets less than $100 000 were both associated with greater MFH. MFH at 3 months was associated with decreased social functioning and quality of life at 6 months.

Conclusions
Nearly 3 out of 4 mCRC patients experienced MFH despite access to health insurance. These findings underscore the need for clinic and policy solutions that protect cancer patients from financial harm.
An Imaging Biomarker of Tumor-Infiltrating Lymphocytes to Risk-Stratify Patients With HPV-Associated Oropharyngeal Cancer
Authors: Corredor Germán , Toro Paula , Koyuncu Can , Lu Cheng , Buzzy Christina , Bera Kaustav , Fu Pingfu , Mehrad Mitra , Ely Kim A , Mokhtari Mojgan , Yang Kailin , Chute Deborah , Adelstein David J , Thompson Lester D R , Bishop Justin A , Faraji Farhoud , Thorstad Wade , Castro Patricia , Sandulache Vlad , Koyfman Shlomo A , Lewis James S , Madabhushi Anant 
Published: November 2021

Abstract

Background
Human papillomavirus (HPV)–associated oropharyngeal squamous cell carcinoma (OPSCC) has excellent control rates compared to nonvirally associated OPSCC. Multiple trials are actively testing whether de-escalation of treatment intensity for these patients can maintain oncologic equipoise while reducing treatment-related toxicity. We have developed OP-TIL, a biomarker that characterizes the spatial interplay between tumor-infiltrating lymphocytes (TILs) and surrounding cells in histology images. Herein, we sought to test whether OP-TIL can segregate stage I HPV-associated OPSCC patients into low-risk and high-risk groups and aid in patient selection for de-escalation clinical trials.

Methods
Association between OP-TIL and patient outcome was explored on whole slide hematoxylin and eosin images from 439 stage I HPV-associated OPSCC patients across 6 institutional cohorts. One institutional cohort (n = 94) was used to identify the most prognostic features and train a Cox regression model to predict risk of recurrence and death. Survival analysis was used to validate the algorithm as a biomarker of recurrence or death in the remaining 5 cohorts (n = 345). All statistical tests were 2-sided.

Results
OP-TIL separated stage I HPV-associated OPSCC patients with 30 or less pack-year smoking history into low-risk (2-year disease-free survival [DFS] = 94.2%; 5-year DFS = 88.4%) and high-risk (2-year DFS = 82.5%; 5-year DFS = 74.2%) groups (hazard ratio = 2.56, 95% confidence interval = 1.52 to 4.32; P &lt; .001), even after adjusting for age, smoking status, T and N classification, and treatment modality on multivariate analysis for DFS (hazard ratio = 2.27, 95% confidence interval = 1.32 to 3.94; P = .003).

Conclusions
OP-TIL can identify stage I HPV-associated OPSCC patients likely to be poor candidates for treatment de-escalation. Following validation on previously completed multi-institutional clinical trials, OP-TIL has the potential to be a biomarker, beyond clinical stage and HPV status, that can be used clinically to optimize patient selection for de-escalation.
Updated Guidance on Use and Prioritization of Monoclonal Antibody Therapy for Treatment of COVID-19 in Adolescents
Authors: Wolf Joshua , Abzug Mark J , Anosike Brenda I , Vora Surabhi B , Waghmare Alpana , Sue Paul K , Olivero Rosemary M , Oliveira Carlos R , James Scott H , Morton Theodore H , Maron Gabriela M , Young Jennifer L , Orscheln Rachel C , Schwenk Hayden T , Bio Laura L , Willis Zachary I , Lloyd Elizabeth C , Hersh Adam L , Huskins Charles W , Soma Vijaya L , Ratner Adam J , Hayes Molly , Downes Kevin , Chiotos Kathleen , Grapentine Steven P , Wattier Rachel L , Lamb Gabriella S , Zachariah Philip , Nakamura Mari M 
Published: November 2021

Abstract

Background
Starting in November 2020, the US Food and Drug Administration (FDA) has issued Emergency Use Authorizations (EUAs) for multiple novel virus-neutralizing monoclonal antibody therapies, including bamlanivimab monotherapy (now revoked), bamlanivimab and etesivimab, casirivimab and imdevimab (REGEN-COV), and sotrovimab, for treatment or postexposure prophylaxis of Coronavirus disease 2019 (COVID-19) in adolescents (≥12 years of age) and adults with certain high-risk conditions. Previous guidance is now updated based on new evidence and clinical experience.

Methods
A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacotherapy, and pediatric critical care medicine from 18 geographically diverse US institutions was convened. Through a series of teleconferences and web-based surveys, a guidance statement was developed and refined based on a review of the best available evidence and expert opinion.

Results
The course of COVID-19 in children and adolescents is typically mild, though more severe disease is occasionally observed. Evidence supporting risk stratification is incomplete. Randomized controlled trials have demonstrated the benefit of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific monoclonal antibody therapies in adults, but data on safety and efficacy in children or adolescents are limited. Potential harms associated with infusion reactions or anaphylaxis are reportedly low in adults.

Conclusions
Based on evidence available as of August 31, 2021, the panel suggests a risk-based approach to administration of SARS-CoV-2 monoclonal antibody therapy. Therapy is suggested for the treatment of mild to moderate COVID-19 in adolescents (≥12 years of age) at the highest risk of progression to hospitalization or severe disease. Therapeutic decision-making about those at moderate risk of severe disease should be individualized. Use as postexposure prophylaxis could be considered for those at the highest risk who have a high-risk exposure but are not yet diagnosed with COVID-19. Clinicians and health systems should ensure safe and timely implementation of these therapeutics that does not exacerbate existing healthcare disparities.
Perinuclear positioning of endosomes can affect PS-ASO activities
Authors: Liang Xue-hai , Nichols Joshua G , Tejera Dario , Crooke Stanley T 
Published: November 2021

Abstract
Phosphorothioate (PS) modified antisense oligonucleotide (ASO) drugs that act on cellular RNAs must enter cells and be released from endocytic organelles to elicit antisense activity. It has been shown that PS-ASOs are mainly released by late endosomes. However, it is unclear how endosome movement in cells contributes to PS-ASO activity. Here, we show that PS-ASOs in early endosomes display Brownian type motion and migrate only short distances, whereas PS-ASOs in late endosomes (LEs) move linearly along microtubules with substantial distances. In cells with normal microtubules and LE movement, PS-ASO-loaded LEs tend to congregate perinuclearly. Disruption of perinuclear positioning of LEs by reduction of dynein 1 decreased PS-ASO activity, without affecting PS-ASO cellular uptake. Similarly, disruption of perinuclear positioning of PS-ASO-LE foci by reduction of ER tethering proteins RNF26, SQSTM1 and UBE2J1, or by overexpression of P50 all decreased PS-ASO activity. However, enhancing perinuclear positioning through reduction of USP15 or over-expression of RNF26 modestly increased PS-ASO activity, indicating that LE perinuclear positioning is required for ensuring efficient PS-ASO release. Together, these observations suggest that LE movement along microtubules and perinuclear positioning affect PS-ASO productive release.