bluuebunny/crossref_metadata_2025_split huggingface dataset:
New scoring systems for predicting advanced proximal neoplasia in asymptomatic adults with or without knowing distal colorectal findings: a prospective, cross-sectional study
Authors: Imperiale Thomas F. , Monahan Patrick O. , Stump Timothy E. , Ransohoff David F. 
Published: September 2021

Background
Models estimating risk for advanced proximal colorectal neoplasia (APN) may be used to select colorectal cancer (CRC) screening test, either prior to knowing distal colorectal findings or afterward. Current models have only fair discrimination and nearly all require knowing distal findings.

Objective
Derive and test risk prediction models for APN with and without distal findings.

Setting
Selected endoscopy centers within central Indiana, USA.

Participants
Average-risk persons undergoing first-time screening colonoscopy

Interventions
Demographics, personal and family medical history, lifestyle factors and physical measures were linked to the most advanced finding in proximal and distal colorectal segments. For both models, logistic regression identified factors independently associated with APN on a derivation set. Based on equation coefficients, points were assigned to each factor, and risk for APN was examined for each score. Scores with comparable risks were collapsed into risk categories. Both models and their scoring systems were tested on the validation set.

Main outcome
APN, defined as any adenoma or sessile serrated lesion ≥1 cm, one with villous histology or high-grade dysplasia, or CRC proximal to the descending colon.

Results
Among 3025 subjects in the derivation set (mean age 57.3 ± 6.5 years; 52% women), APN prevalence was 4.5%; 2859 (94.5%) had complete data on risk factors. Independently associated with APN were age, sex, cigarette smoking, cohabitation status, metabolic syndrome, non-steroidal anti-inflammatory drug use and physical activity. This model (without distal findings) was well-calibrated (P = 0.62) and had good discrimination (c-statistic = 0.73). In low-, intermediate- and high-risk groups that comprised 21, 58 and 21% of the sample, respectively, APN risks were 1.47% (95% CI, 0.67–2.77%), 3.09% (CI, 2.31–4.04%) and 11.6% (CI, 9.10–14.4%), respectively (P < 0.0001), with no proximal CRCs in the low-risk group and 2 in the intermediate-risk group. When tested in the validation set of 1455, the model retained good metrics (calibration P = 0.85; c-statistic = 0.83), with APN risks in low- (22%), intermediate- (56%) and high-risk (22%) subgroups of 0.62% (CI, 0.08–2.23%) 2.20% (CI, 1.31–3.46%) and 13.0% (CI, 9.50–17.2%), respectively (P < 0.0001). There were no proximal CRCs in the low-risk group, and two in the intermediate-risk group. The model with distal findings performed comparably, with validation set metrics of 0.18 for calibration, 0.76 for discrimination and APN risk (% sample) in low-, intermediate-, and high-risk groups of 1.1 (69%), 8.3 (22%) and 22.3% (9%).

Conclusion
These models stratify large proportions of average-risk persons into clinically meaningful risk groups, and could improve screening efficiency, particularly for noncolonoscopy-based programs.
Psychotropic prescribing rates and pharmacogenomic testing implications for autism in the Canadian primary care sentinel surveillance network
Authors: Ahmed Zeeshan , Hao Sylvia , Williamson Tyler , McMorris Carly A. , Bousman Chad A. 
Published: September 2021

Objective
To estimate prescribing rates of psychotropic drugs to individuals with autism and the proportion of these individuals who could benefit from pharmacogenetic testing.

Methods
Prescribing data for 92 psychotropic drugs, including 31 antidepressants, 22 antipsychotics, 14 mood stabilizer/antiepileptics, 17 anxiolytic/hypnotics and eight antiadrenergic/psychostimulant were retrieved from medical records of 787 (613 males) autistic individuals who sought treatment from a primary care office enrolled in the Canadian Primary Care Sentinel Surveillance Network between 2012 and 2014. Each prescribed drug was cross-referenced with pharmacogenomic-based prescribing guidelines published by the Clinical Pharmacogenetics Implementation Consortium, the Dutch Pharmacogenetics Working Group, and the Canadian Pharmacogenomics Network for Drug Safety.

Results
More than half (58%) of the participants were prescribed a psychotropic drug and 37% were prescribed two or more psychotropic drugs concurrently. Among the 83 psychotropic drugs examined, 54 (65%) were prescribed to one or more participants during the study’s observation period. The ten most frequently prescribed psychotropics were methylphenidate (16.3%), risperidone (12.8%), lorazepam (12.1%), fluoxetine (7.9%), sertraline (7.1%), quetiapine (6.9%), aripiprazole (6.1%), lisdexamfetamine (5.8%), citalopram (5.6%) and clonazepam (4.8%). Seventeen (32%) of the 54 psychotropic drugs prescribed were linked to a pharmacogenomic-based prescribing guideline, including risperidone, sertraline, aripiprazole and citalopram.

Conclusions
Our findings suggest primary care providers in Canada prescribe a wide range of psychotropics to their patients with autism, some of which may benefit from the integration of pharmacogenomic information into their treatment planning.
Postoperative delirium and neurocognitive disorders
Authors: Migirov Allan , Chahar Praveen , Maheshwari Kamal 
Published: September 2021

Purpose of review
Postoperative neurocognitive disorders (NCD) are significant causes of morbidity and mortality. In this paper, we will review our understanding and potential management of postoperative NCD.

Recent findings
Postoperative delirium, delayed neurocognitive recovery and postoperative cognitive dysfunction (POCD) are recognized as a part of the continuous spectrum of postoperative NCD. Although the pathophysiology is still poorly understood, there is renewed focus on improving neurocognitive outcomes of aging surgical population. Novel methods of neurocognitive screening are developed and research in the prevention and management of NCD has gained traction.

Summary
A spectrum of NCD exists in surgical patients ranging from postoperative delirium, delayed neurocognitive recovery, and POCD. Identification of patients at-risk for developing NCD can help target appropriate perioperative intervention. Also, specialized care teams and the implementation of standardized protocols are crucial for the successful management perioperative NCD. Finally, large, randomized, multicenter studies are needed to confirm benefits of preventive and treatment strategies
Management of patients with unilateral microtia and aural atresia: recent advances and updates
Authors: Ikeda Allison K. , Bhrany Amit D. , Sie Kathleen C.Y. , Bly Randall A. 
Published: September 2021

Purpose of review
The management of patients with unilateral microtia and aural atresia is complex. Recent literature suggests significant strides in hearing habilitation and ear reconstruction.

Recent findings
Several options of hearing management are available and are associated with improved outcomes. Timelines for hearing habilitation and ear reconstruction vary by institution. We offer our timeline as a reference. Three dimensional (3D) printed models are increasingly used for training and reconstruction. Bioprinting is on the horizon, though safety and effectiveness studies are pending. Lastly, application of qualitative methods has provided a foundation on which to improve communication between physicians and patients and their families. Better understanding of the patient and family experiences will provide opportunities to target interventions to improve care.

Summary
Current developments include expanding options for hearing management, changing approaches to timing of atresiaplasty, utilization of 3D printed models, and focus on patient and family experience to improve reconstructive outcomes.
Clinical Practice Guidelines for the Management of Patients With Cleft Lip and Palate: A Systematic Quality Appraisal Using the Appraisal of Guidelines for Research and Evaluation II Instrument
Authors: Yver Christina M. , Chorath Kevin T. , Connolly John , Shah Mitali , Majmudar Tanmay , Moreira Alvaro G. , Rajasekaran Karthik 
Published: September 2021

Abstract
Patients with cleft lip and/or palate require complex and longitudinal care by a multidisciplinary cleft team. Unfortunately, delivery of cleft care is often fragmented, and care practices can vary significantly. Multiple clinical practice guidelines (CPGs) have been proposed to provide a standardized framework for cleft care delivery. As CPGs have gained popularity, there has been increasing demand to maintain the quality of existing guidelines. A comprehensive search of EMBASE, MEDLINE via PubMed, Scopus, Cochrane and grey literature sources published from January 1, 1990 to December 31, 2020 was conducted to identify CPGs for the care of cleft patients. The Appraisal of Guidelines for Research and Evaluation, 2nd edition II tool was used to assess the quality of selected CPGs. Intraclass coefficients were calculated to assess agreement among appraisers. Eleven guidelines were identified for study inclusion. One guideline was classified as “high” quality by Appraisal of Guidelines for Research and Evaluation II criteria, and the remaining guidelines were classified as “average” or “low” quality. The “Clarity of Presentation” domain achieved the highest mean score (76.9% ± 11.7%) across CPGs, whereas the “Rigor of Development” domain scored the lowest (35.6% ± 21.2%). Intraclass coefficients analysis reflected very good inter-rater reliability across all domains (0.853–0.987). These findings highlight significant variability in the quality of existing CPGs for the global management of patients with cleft lip and/or palate. The “Rigor of Development” domain reflects the greatest opportunity for improvement. Given these findings, future guidelines may prioritize incorporating a systematic review of existing evidence into recommendations.
A New Technique of Open Septal Reduction Using Polydioxanone Plates for Nasoseptal Fracture: Three-Dimensional Volumetric Analysis
Authors: Kim Kyubeom , Kim Jaehoon , Kim Junhyung , Yun Insik , Jo Taehee , Choi Jaehoon , Jeong Woonhyeok 
Published: September 2021

Background:
In this study, we designed a new technique for open septal reduction using a polydioxanone (PDS) plate and compared it with closed reduction (CR).

Methods:
This study included 19 consecutive patients with nasoseptal fracture: 10 receiving open reduction with a PDS plate (PDS group) and 9 undergoing CR group. Open septal reduction was performed after CR for nasal bone fracture. A mucoperichondrial flap was unilaterally elevated, and the deviated septal cartilage was reduced. The PDS plate was inserted horizontally above the vomerine suture. Surgical outcome was analyzed with three-dimensional volumetry and with a quality-of-life scale for nasal obstruction (Nasal Obstruction Symptom Evaluation scale).

Results:
Complications included 1 case of septal perforation in the CR group and 1 case of PDS exposure and septal hematoma in the PDS group. In the three-dimensional volumetric analysis of the PDS group, the median value of the nasal cavity change significantly differed between 1.14 mL (interquartile range; 0.46–2.4) at the preoperative computed tomography scan and 0.33 mL (interquartile range; −0.22 to 1.29) at the postoperative computed tomography scan (∗∗
P = 0.0039). The Nasal Obstruction Symptom Evaluation scale revealed significant improvement in nasal obstruction postsurgically (median value, 42.5–7.5; ∗
P = 0.0139) in the PDS group.

Conclusions:
Polydioxanone plates potentially present a new concept of open septal reduction in terms of septal reinforcement compared with the subtractive approach of open septal reduction.
Quantitative measurement of infectious virus in SARS-CoV-2 Alpha, Delta and Epsilon variants reveals higher infectivity (viral titer:RNA ratio) in clinical samples containing the Delta and Epsilon variants
Authors: Despres Hannah W. , Mills Margaret G. , Shirley David J. , Schmidt Madaline M. , Huang Meei-Li , Jerome Keith R. , Greninger Alexander L. , Bruce Emily A. 
Published: September 2021

ABSTRACTBackgroundNovel SARS-CoV-2 Variants of Concern (VoC) pose a challenge to controlling the COVID-19 pandemic. Previous studies indicate that clinical samples collected from individuals infected with the Delta variant may contain higher levels of RNA than previous variants, but the relationship between viral RNA and infectious virus for individual variants is unknown.MethodsWe measured infectious viral titer (using a micro-focus forming assay) as well as total and subgenomic viral RNA levels (using RT-PCR) in a set of 165 clinical samples containing SARS-CoV-2 Alpha, Delta and Epsilon variants that were processed within two days of collection from the patient.ResultsWe observed a high degree of variation in the relationship between viral titers and RNA levels. Despite the variability we observed for individual samples the overall infectivity differed among the three variants. Both Delta and Epsilon had significantly higher infectivity than Alpha, as measured by the number of infectious units per quantity of viral E gene RNA (6 and 4 times as much, p=0.0002 and 0.009 respectively) or subgenomic E RNA (11 and 7 times as much, p<0.0001 and 0.006 respectively).ConclusionIn addition to higher viral RNA levels reported for the Delta variant, the infectivity (amount of replication competent virus per viral genome copy) may also be increased compared to Alpha. Measuring the relationship between live virus and viral RNA is an important step in assessing the infectivity of novel SARS-CoV-2 variants. An increase in the infectivity of the Delta variant may further explain increased spread and suggests a need for increased measures to prevent viral transmission.SIGNIFICANCE STATEMENTCurrent and future SARS-CoV-2 variants threaten our ability to control the COVID-19 pandemic. Variants with increased transmission, higher viral loads, or greater immune evasion are of particular concern. Viral loads are currently measured by the amount of viral RNA in a clinical sample rather than the amount of infectious virus. We measured both RNA and infectious virus levels directly in a set of 165 clinical specimens from Alpha, Epsilon or Delta variants. Our data shows that Delta is more infectious compared to Alpha, with ∼ six times as much infectious virus for the same amount of RNA. This increase in infectivity suggests increased measures (vaccination, masking, distancing, ventilation) are needed to control Delta compared to Alpha.
Impact of multiple sclerosis disease-modifying therapies on SARS-CoV-2 vaccine-induced antibody and T cell immunity
Authors: Sabatino Joseph J. , Mittl Kristen , Rowles William , Mcpolin Kira , Rajan Jayant V. , Zamecnik Colin R. , Dandekar Ravi , Alvarenga Bonny D. , Loudermilk Rita P. , Gerungan Chloe , Spencer Collin M. , Sagan Sharon A. , Augusto Danillo G. , Alexander Jessa , Hollenbach Jill A. , Wilson Michael R. , Zamvil Scott S. , Bove Riley 
Published: September 2021

AbstractVaccine-elicited adaptive immunity is an essential prerequisite for effective prevention and control of coronavirus 19 (COVID-19). Treatment of multiple sclerosis (MS) involves a diverse array of disease-modifying therapies (DMTs) that target antibody and cell-mediated immunity, yet a comprehensive understanding of how MS DMTs impact SARS-CoV-2 vaccine responses is lacking. We completed a detailed analysis of SARS-CoV-2 vaccine-elicited spike antigen-specific IgG and T cell responses in a cohort of healthy controls and MS participants in six different treatment categories. Two specific DMT types, sphingosine-1-phosphate (S1P) receptor modulators and anti-CD20 monoclonal antibodies (mAb), resulted in significantly reduced spike-specific IgG responses. Longer duration of anti-CD20 mAb treatment prior to SARS-CoV-2 vaccination were associated with absent antibody responses. Except for reduced CD4+ T cell responses in S1P-treated patients, spike-specific CD4+ and CD8+ T cell reactivity remained robust across all MS treatment types. These findings have important implications for clinical practice guidelines and vaccination recommendations in MS patients and other immunosuppressed populations.
Effects of short-term salinity exposure on haemolymph osmolality, gill morphology and Na+/K+ - ATPase activity in Solenaia oleivora
Authors: Yao Jingting , Zhang Ting , Xu Dongpo , Lv Guohua , Jin Wu , Ma Xueyan , Zhou Yanfeng , Gu Ruobo , Wen Haibo 
Published: September 2021

AbstractIn order to explore the physiological reaction to hyperosmotic environment, Solenaia oleivora were exposed to 2.23‰ salinity. In 48h, the hemolymph osmolality kept increasing, and the hemolymph protein concentration increased in the first 6h and then decreased significantly, while the free amino acid content increased in the first 24h and then kept stable (P < 0.05). The activity of Na+/K+-ATPase at 0h was significantly higher than other times in most organs except intestine, which was highest at 3h (P < 0.05). The ions concentration were also influenced. The concentration of Na+ rose in haemolymph, axe foot and intestine, but decreased in gill and hepatopancreas. In hemolymph, gill, hepatopancreases and adductor muscle, the K+ concentration was the highest at 0h, while in axe foot and intestine, it showed a positive tendency. The concentration of Cl- in haemolymph, adductor muscle, intestine and axe foot were positively correlated with treatment time, while hepatopancreas showed opposite tendency. High salinity stress caused a difference in the gill histological structure, the gill structure shrunk, the gill lamellas space and shrinking degree showed an enlarging trend with salinity treatment time.
Proton pump inhibitors use and risk of preeclampsia
Authors: Hussain Salman , Singh Ambrish , Antony Benny , Klugarová Jitka , Klugar Miloslav 
Published: September 2021

AbstractPreeclampsia is one of the common complications of pregnancy and is characterized by high blood pressure. Proton pump inhibitors (PPIs) are commonly used for the management of gastroesophageal reflux disease among pregnant women. Recently, multiple epidemiological studies suggested the association between PPIs use and the risk of preeclampsia. This study aims to review the evidence and meta-analyse the pooled risk of preeclampsia in PPI users from epidemiological studies. Databases-MEDLINE, Embase, Scopus, Web of Science Core Collection, Emcare, and CINAHL (EBSCO) as well as sources of grey literature, ProQuest Dissertations & Theses Global,ClinicalTrials.govand WHO International Clinical Trials Registry Platform will be searched to identify the epidemiological studies assessing the association between PPIs use and the risk of preeclampsia. Study selection, data extraction, and quality assessment will be performed by two independent authors. The risk of bias among included studies will be evaluated by using the Newcastle-Ottawa scale. The pooled effect of PPIs use on the risk of preeclampsia in pregnant women is the primary outcome of interest. Meta-analysis will be performed using Review Manager version 5.4.
COVID-19 Vaccination and Healthcare Demand
Authors: Betti Matthew I. , Abouleish Amira Hassan , Spofford Victoria , Peddigrew Cory , Diener Alan , Heffernan Jane M. 
Published: September 2021

AbstractOne of the driving concerns during any epidemic is the strain on the healthcare system. As we have seen many times over the globe with the COVID-19 pandemic, hospitals and ICUs can quickly become overwhelmed by cases. While strict periods of public health mitigation have certainly helped decrease incidence and thus healthcare demand, vaccination is the only clear long-term solution. In this paper, we develop a two-module model to forecast the effects of relaxation of non-pharmaceutical intervention and vaccine uptake on daily incidence, and the cascade effects on healthcare demand. The first module is a simple epidemiological model which incorporates non-pharmaceutical intervention, the relaxation of such measures and vaccination campaigns to predict caseloads into the the Fall of 2021. This module is then fed into a healthcare module which can forecast the number of doctor visits, the number of occupied hospital beds, number of occupied ICU beds and any excess demand of these. From this module we can also estimate the length of stay of individuals in ICU. For model verification and forecasting, we use the four most populous Canadian provinces as a case study.
SARS-CoV-2 wastewater surveillance in Germany: long-term PCR monitoring, suitability of primer/probe combinations and biomarker stability
Authors: Ho Johannes , Stange Claudia , Suhrborg Rabea , Wurzbacher Christian , Drewes Jörg E. , Tiehm Andreas 
Published: September 2021

AbstractIn recent months, wastewater-based epidemiology (WBE) has been shown to be an important tool for early detection of SARS-CoV-2 circulation in the population. In this study, a detection methodology for SARS-CoV-2 RNA (wild-type and variants of concern) in wastewater was developed based on the detection of different target genes (E and ORF1ab) by PEG precipitation and digital droplet PCR. This methodology was used to determine the SARS-CoV-2 concentration and the proportion of N501Y mutation in raw sewage of the wastewater treatment plant of the city of Karlsruhe in southwestern Germany over a period of 1 year (June 2020 to July 2021). Comparison of SARS-CoV-2 concentrations with reported COVID-19 cases in the catchment area showed a significant correlation. Viral RNA titre trends appeared more than 12 days earlier than clinical data, demonstrating the potential of wastewater-based epidemiology as an early warning system. Parallel PCR analysis using seven primer and probe systems revealed similar gene copy numbers with E, ORF, RdRP2 and NSP9 assays. RdPP1 and NSP3 generally resulted in lower copy numbers, and in particular for N1 there was low correlation with the other assays due to outliers. The occurrence of the N501Y mutation in the wastewater of Karlsruhe was consistent with the occurrence of the alpha-variant (B.1.1.7) in the corresponding individual clinical tests. In batch experiments SARS-CoV-2 RNA was stable for several days under anaerobic conditions, but the copy numbers decreased rapidly in the presence of dissolved oxygen. Overall, this study shows that wastewater-based epidemiology is a sensitive and robust approach to detect trends in the spread of SARS-CoV-2 at an early stage, contributing to successful pandemic management.