bluuebunny/crossref_metadata_2025_split huggingface dataset:
Specific mutations in the HIV-1 G-tract of the 3′-polypurine tract cause resistance to integrase strand transfer inhibitors
Authors: Hachiya Atsuko , Kubota Mai , Shigemi Urara , Ode Hirotaka , Yokomaku Yoshiyuki , Kirby Karen A , Sarafianos Stefan G , Iwatani Yasumasa 
Published: December 2021

Abstract

Background
In vitro selection experiments identified viruses resistant to integrase strand transfer inhibitors (INSTIs) carrying mutations in the G-tract (six guanosines) of the 3′-polypurine tract (3′-PPT). A clinical study also reported that mutations in the 3′-PPT were observed in a patient receiving dolutegravir monotherapy. However, recombinant viruses with the 3′-PPT mutations that were found in the clinical study were recently shown to be susceptible to INSTIs.

Objectives
To identify the specific mutation(s) in the G-tract of the 3′-PPT for acquiring INSTI resistance, we constructed infectious clones bearing single or multiple mutations and systematically characterized the susceptibility of these clones to both first- and second-generation INSTIs.

Methods
The infectious clones were tested for their infectivity and susceptibility to INSTIs in a single-cycle assay using TZM-bl cells.

Results
A single mutation of thymidine (T) at the fifth position (GGG GTG) in the G-tract of the 3′-PPT had no effect on INSTI resistance. A double mutation, cytidine (C) or ‘T’ at the second position and ‘T’ at the fifth position (GCG GTG and GTG GTG), increased resistance to INSTIs, with the appearance of a plateau in the maximal percentage inhibition (MPI) of the dose–response curves, consistent with a non-competitive mechanism of inhibition.

Conclusions
Mutations at the second and fifth positions in the G-tract of the 3′-PPT may result in complex resistance mechanism(s), rather than simply affecting INSTI binding at the IN active site.
Mortality in patients with carbapenem-resistantPseudomonas aeruginosawith and without susceptibility to traditional antipseudomonal β-lactams
Authors: Howard-Anderson Jessica , Bower Chris W , Smith Gillian , Satola Sarah W , Jacob Jesse T 
Published: December 2021

AbstractBackgroundCarbapenem-resistant Pseudomonas aeruginosa (CRPA) isolates can frequently retain susceptibility to traditional antipseudomonal β-lactams including cefepime, ceftazidime and piperacillin/tazobactam.ObjectivesThis observational study aimed to determine the proportion of CRPA isolates that were susceptible to all tested other traditional antipseudomonal β-lactams (S-CRPA) and assess whether patients with S-CRPA had improved 30 day mortality compared with patients with NS-CRPA (non-susceptible to cefepime, ceftazidime or piperacillin/tazobactam).MethodsPatients with CRPA isolated from normally sterile sites, urine, lower respiratory tracts and wounds were identified using active population- and laboratory-based surveillance through the Georgia Emerging Infections Program from August 2016 to July 2018 in Atlanta, GA, USA. Only unique patients who were hospitalized at the time of, or within 1 week of, culture were included. We excluded patients with cystic fibrosis. Multivariable logistic regression estimated the association between S-CRPA and 30 day mortality.ResultsAmong 635 adults hospitalized with CRPA, 219 (34%) had S-CRPA. Patients with S-CRPA were more likely to be white (50% versus 38%, P = 0.01) and live in a private residence prior to culture (44% versus 28%, P &lt; 0.01), and less likely to have required ICU care within the prior week (23% versus 36%, P &lt; 0.01) compared with patients with NS-CRPA. Compared with those with NS-CRPA, patients with S-CRPA had an increased 30 day mortality (18% versus 15%, adjusted OR 1.9; 95% CI 1.2–3.1).ConclusionsS-CRPA was associated with higher 30 day mortality than NS-CRPA in hospitalized patients. The reason for this observed increase in mortality deserves further investigation.
Optimization and Validation of a Multiresidue Method for Screening of 126 Pesticide Residues in Herbal Raw Materials and Extracts Used as Ingredients in Ayurvedic Medicines and Dietary Supplements
Authors: Koshy Rojison , Yadav Smriti , Rajeshkumar Rajendran , Singh Vineet Kumar , Setty Manjunath M , Murali Balasubramanian , Agarwal Amit 
Published: December 2021

Abstract

Background
Testing for pesticide levels in herbal products is an important aspect in determining product safety. Plants and their extracts are widely used as ingredients in botanical dietary supplements and traditional medicines. The extracts of plants, especially those prepared out of organic solvents, are rich in secondary metabolites and pigments, and adequate clean-up is required since the extracts completely dissolve in organic solvents.

Objective
The study aims at reporting a multiresidue analytical method for 126 different pesticides in raw material biomass as well as extracts of plants, which are widely used as ingredients in ayurvedic medicines as well as dietary supplements using LC-MS/MS and GC-MS/MS with a rugged sample preparation technique for accurate results.

Method
QuEChERS (quick, easy, cheap,effective, rugged, and safe) procedure, gel permeation chromatography (GPC), GPC coupled with solid phase extraction (SPE), and liquid-liquid extraction (LLE) coupled with SPE sample preparation methods were compared against each other for suitability to test pesticides in selected herbal raw materials and their alcoholic and aqueous extracts. The standard addition method was used for quantifying the level of pesticides below 10 μg/kg.

Results
Single laboratory validation for sample preparation involving GPC and SPE resulted linearity in the range of 2.5–500 ng/mL, average intraday and interday precision of 6.6% RSD, and average recovery (spiked at 10 μg/kg) of 92% for all analytes tested. The method was repeatable with different analysts and days.

Conclusions
The sample preparation technique combining GPC and SPE as well as LLE and SPE was the most suitable for the selected herbal alcoholic extracts, whereas any of the regular techniques involving LLE, SPE, and QuEChERS were suitable for raw material biomass as well as aqueous extracts.

Highlights
The method was found to be capable of determining selected pesticides in the selected matrixes at 10 μg/kg concentration. Provision of recycling solvents used in the GPC+SPE method was adopted to make the method environmentally friendly.
Effects of supplementing low-protein diets with sodium dichloroacetate and glucose on growth performance, carcass traits, and meat quality of growing-finishing pigs
Authors: Xu Yetong , Chen Huiyuan , Wan Ke , Zhou Kaifeng , Wang Yongsheng , Li Jigang , Tang Zhiru , Sun Weizhong , Wu Liuting , An Rui , Ren Zhongxiang , Ding Qi , Liang Kaiyang , Sun Zhihong 
Published: December 2021

Abstract
The objective of this study was to evaluate the effects of supplementing low-protein diets with sodium dichloroacetate (DCA) and glucose on growth performance, carcass traits, and meat quality of growing-finishing pigs. A total of 80 crossbred (Duroc × Landrace × Large White) growing barrows (27 ± 0.4 kg body weight) were allocated randomly to one of the five treatments during three successive 4-wk periods. There were five diets in each phase. Diet 1 was the control diet with normal protein levels (CON) where protein levels in the three phases were 18%, 16.5%, and 15.5%, respectively. The dietary protein levels of Diets 2, 3, 4, and 5 (the low-protein diets, LP) were decreased by 4.5% compared to Diet 1. Additionally, Diets 3 and 4 were supplemented with an extra 120 mg/kg DCA (LP + DCA) or 1.8% glucose (LP + GLUC), respectively. Diet 5 was further supplemented with an extra 120 mg/kg DCA and 1.8% glucose (LP + DCA + GLUC). The LP + DCA diet increased the average daily weight gain of pigs compared to the CON and LP diet in phase 3 and the overall experimental period (P &lt; 0.001). The LP diet reduced the gain:feed ratios of the pigs compared to the CON, LP + DCA, and LP + DCA + GLUC diets in phase 1 and the overall experimental period (P &lt; 0.001). Furthermore, gain:feed ratios in LP + DCA and LP + DCA + GLUC groups did not differ from that of the CON group (P &gt; 0.10). Pigs fed the LP + DCA diet had higher pH values of meat at 24 h post-mortem than the CON group (P &lt; 0.05). The LP + DCA + GLUC diet increased the total protein content in the longissimus dorsi (LD) muscle of pigs, compared to the other dietary treatments (P &lt; 0.05), and increased the Arg and Leu contents in the LD muscle compared to the LP + DCA diet (P &lt; 0.05). Moreover, the LP + DCA diet induced a higher C18:1n9t percentage in the LD muscle of pigs compared to other groups (P &lt; 0.05). In conclusion, an LP diet reduced the feed efficiency in pigs and barely affected meat quality, whereas 120 mg/kg DCA supplementation in an LP diet improved the growth performance of growing-finishing pigs, showed modest effects on carcass traits, and improved the muscle protein content with the addition of glucose.
Detection ofLeishmania donovaniin Wild-Caught Phlebotomine Sand Flies in Endemic Focus of Leishmaniasis in Himachal Pradesh, India
Authors: Lata Suman , Kumar Gaurav , Ojha V P , Dhiman Ramesh C 
Published: December 2021

AbstractAn endemic focus of cutaneous leishmaniasis (CL) is located in the Sutlej River Valley in Himachal Pradesh (India) in the north-western Himalaya where CL co-exists with visceral leishmaniasis (VL). In areas of the Indian subcontinent such as Rajasthan, cutaneous leishmaniasis is transmitted by Phlebotomus papatasi (Scopoli) and Phlebotomus salehi. In Himachal Pradesh, Phlebotomus longiductus (Parrot) is suspected to be the vector for CL. In the current study, sand flies were collected and tested for Leishmania infection and to confirm the vector species causing CL. Sand flies were collected during April and September of 2017–2019 from CL endemic villages of Rampur (Shimla), Nirmand (Kullu) and Nichar (Kinnaur) districts of Himachal Pradesh. The sand flies were identified as Phlebotomus (adlerius) longiductus (Parrot) and Phlebotomus (larrousisus) major (Annandale). The density of P. longiductus was found highest. The elevation of villages ranged from 947 m to 2,130 m and were far from the presence of subsoil water. Field collected sand flies tested positive (7.69%) for Leishmania donovani by PCR-RFLP. The L. donovani sequences detected from P. longiductus were 97% similar to L. donovani sequences reported from the cases of CL in Himachal Pradesh.The Leishmania positive sand flies were morphologically identified as Phlebotomus adlerious longiductus providing one step further evidence towards the vector status of CL in Himachal Pradesh. The findings of the study are of epidemiological significance for strategic planning of vector control for leishmaniasis in India.
A Content Analysis of American Primetime Television: A 20-Year Update of the National Television Violence Studies
Authors: Riddle Karyn , Martins Nicole 
Published: December 2021

AbstractThis article provides a 20-year, apples-to-apples update of the National Television Violence Studies. Using the same sampling procedures and codebook, we coded 765 primetime television programs and movies airing on 21 broadcast and cable networks. Results suggest the prevalence of violence has increased slightly, but the number of programs saturated with violence has experienced a more significant increase. This appears to be driven by an influx of highly violent movies airing in primetime on cable channels. Although some contextual variables suggest slight improvements in terms of negative consequences for violence, the overwhelming majority of violent television programs and movies do not feature anti-violence themes. Implications for social cognitive, cultivation, schema, transportation, and media vividness theories are discussed.
The Miroir des dames in Fifteenth-Century England
Authors: Mattison J R 
Published: December 2021

Abstract
This article outlines the circulation and readership of a continental French text called the Miroir des dames in England during the fifteenth century. Three surviving manuscripts can be connected with England: one belonged to the Duke of Bedford, another to Henry VII, and a third was created in England and copied from Bedford's manuscript. Documentary evidence indicates that at least two further manuscripts of the Miroir circulated in England. These manuscripts and references demonstrate the continued reading and copying of French texts in England among a select circle of bibliophiles.
Inferior Vena Cava Thrombosis, Appendicitis Mimic
Authors: Kaylor Ryan M , Gehrz Joseph A , Gutweiler Alex A , Cortes James S 
Published: December 2021

ABSTRACT
Right lower quadrant abdominal pain is a common presentation to the Emergency Department. While appendicitis is a frequently diagnosed pathology associated with this complaint, there are multiple, well-documented alternatives that must be considered. The authors present a unique case of a 20 year old active duty male who presented with 3 days of acutely worsening right lower quadrant abdominal pain, right flank pain, and anorexia. Following a detailed work-up, computed tomography and magnetic resonance imaging (MRI) demonstrated a bland thrombus within the inferior vena cava (IVC) secondary to a vascular web. This case highlights the difficulty in astutely diagnosing appendicitis utilizing clinical examination and scoring metrics. While IVC thrombosis is a rare phenomenon, it should be considered in the emergency physician’s differential for right lower quadrant abdominal pain, particularly when additional nonspecific symptoms are present.
Increased replication stress and R-loop accumulation in EGFRvIII-expressing glioblastoma present new therapeutic opportunities
Authors: Struve Nina , Hoffer Konstantin , Weik Anna-Sophie , Riepen Britta , Krug Leonie , Cetin Meryem H , Burmester Jasmin , Ott Leonie , Liebing Jana , Gatzemeier Fruzsina , Müller-Goebel Justus , Gerbach Mirja , Bußmann Lara , Parplys Ann Christin , Unger Kristian , Mansour Wael Y , Schüller Ulrich , Rieckmann Thorsten , Petersen Cordula , Rothkamm Kai , Short Susan C , Kriegs Malte 
Published: December 2021

Abstract

Background
The oncogene epidermal growth factor receptor variant III (EGFRvIII) is expressed in approximately one-third of all glioblastomas (GBMs). So far it is not clear if EGFRvIII expression induces replication stress in GBM cells, which might serve as a therapeutical target.

Methods
Isogenetic EGFRvIII− and EGFRvIII+ cell lines with endogenous EGFRvIII expression were used. Markers of oncogenic and replication stress such as γH2AX, RPA, 53BP1, ATR, and CHK1 were analyzed using western blot, immunofluorescence, and flow cytometry. The DNA fiber assay was performed to analyze replication, transcription was measured by incorporation of EU, and genomic instability was investigated by micronuclei and CGH-Array analysis. Immunohistochemistry staining was used to detect replication stress markers and R-loops in human GBM samples.

Results
EGFRvIII+ cells exhibit an activated replication stress response, increased spontaneous DNA damage, elevated levels of single-stranded DNA, and reduced DNA replication velocity, which are all indicative characteristics of replication stress. Furthermore, we show here that EGFRvIII expression is linked to increased genomic instability. EGFRvIII-expressing cells display elevated RNA synthesis and R-loop formation, which could also be confirmed in EGFRvIII-positive GBM patient samples. Targeting replication stress by irinotecan resulted in increased sensitivity of EGFRvIII+ cells.

Conclusion
This study demonstrates that EGFRvIII expression is associated with increased replication stress, R-loop accumulation, and genomic instability. This might contribute to intratumoral heterogeneity but may also be exploited for individualized therapy approaches.
2. Space Time Trends of Community Onset Staphylococcus aureus Infections in Children Living in Southeastern United States: 2002-2016
Authors: Immergluck Lilly , geng Ruijin , Li Chaohua , Edelson Mike , Waller Lance , Rust George , Xu Junjun , Ali Fatima , Baltrus Peter , Leong Traci 
Published: December 2021

Abstract

Background
Staphylococcus aureus (S. aureus) remains a serious cause of infections in the United States and worldwide. Methicillin susceptible S. aureus (MSSA) is the cause of half of all health care–associated staphylococcal infections, and Methicillin Resistant S. aureus (MRSA) is the leading cause of community onset skin and soft tissue infections in the US. This study looks at a 15-year trend of community onset (CO)-MRSA and MSSA infections and determines ‘best’ to ‘worst’ infection trends. We identified distinct groups of CO-MRSA and MSSA infection rate trajectories by grouping census tracts of the 20 county Atlanta Metropolitan Statistical Area (MSA) between 2002 to 2016 with similar temporal trajectories.

Methods
This is a retrospective study from 2002-2016, using electronic health records of children living in Atlanta, Georgia with S. aureus infections and relevant US census data (at the census tract level). A group based trajectory model was applied to generate community onset S. aureus trajectory infection groups (low, high, very high) by census tract and were mapped using ArcGIS.

Results
Three CO-MSSA infection groups (low, high, very high) and two CO-MRSA infection groups (low, high) were detected among 909 census tracts in the 20 counties. We found ~74% of all the census tracts with S.aureus occurrence during this time period belonged to low infection rate groups for both MRSA and MSSA, with a higher proportion occurring in the less densely populated counties. Census tracts in DeKalb County, one of Atlanta’s most densely populated areas, had the highest proportion of the worst infection trend patterns (CO-MRSA high or very high, CO-MSSA high or very high).
Trends of Community-Onset MRSA and MSSA Infection Rates Based on Group-based Trajectory Models

Spatial patterns for CO-MRSA and CO-MSSA Trajectory Trends in the Atlanta Metropolitan Area Between 2002 to 2016

Conclusion
Trends of S. aureus infection patterns, stratified by antibiotic resistance over geographic areas and time, identify communities with higher risks for MRSA infection compared to MSSA infection. Further investigation of the determinants of the trajectory groupings and the geographic outliers identified by this study may be a way to target prevention strategies aimed to prevent S. aureus infections.

Disclosures
All Authors: No reported disclosures
50. Pilot Study on Offering HIV Pre-Exposure Prophylaxis (PrEP) to People Who Inject Drugs (PWID) in the Inpatient Setting
Authors: Marryshow Terry A , Caro Jose 
Published: December 2021

Abstract

Background
Due to the ongoing opioid epidemic, PWID represent an increasingly high-risk population for HIV infections in the United States, accounting for 10% of all new HIV diagnoses in 2018 and 12.5% of all deaths among people living with HIV. PrEP is an effective means of preventing HIV, though uptake has been low among PWID, possibly due to low access to care. Inpatient admissions may represent missed opportunities for provision of PrEP to PWID.

Methods
Inpatient prescriptions for tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) from 10/2019 to 8/2020 were analyzed to assess baseline provision of PrEP to PWID. Physicians on the Infectious Diseases ward service were anonymously queried on perceived barriers and their practices regarding provision of PrEP to PWID. PWID admitted from 9/2020 to 5/2021 were approached at bedside, provided counseling on PrEP and offered initiation prior to discharge. We analyzed patient perceptions and acceptance of PrEP.

Results
16 total prescriptions for TDF-FTC were provided at discharge from 10/2019 to 8/2020, with 0 being for PrEP in PWID. The 8 physicians surveyed estimated caring for an average 4 PWID per week of service. 5/8 physicians reported that at least one PWID was offered PrEP during their most recent week of service. The most commonly reported physician barrier to prescribing PrEP was uncertainty regarding adherence and follow up (5/8). 30 patients were approached, with 14 reporting prior knowledge of PrEP. 18 were willing to engage in further education. Only 4 were accepting of PrEP, with 2 provided prescriptions. Of those declining, 13 denied equipment sharing, 4 denied active drug use, 7 stated a commitment to future abstinence, 3 were unwilling to adhere to a daily medication, 2 declined due to concerns of adverse effects and 1 due to concerns regarding stigma.
Table 1. Physician Reported Barriers to Prescribing PrEP (n = 8)

Table 2. Patient Knowledge and Acceptance of PrEP (n = 30)

Table 3. Patient Reasons for Declining PrEP (n = 30)

Conclusion
In this pilot study, few admitted PWID were accepting of PrEP. Attempts to initiate PrEP in PWID in the inpatient setting may not be effective at our institution. The most common reason for declining was low self-perceived risk of HIV acquisition; however, a significant proportion of patients showed interest in further education. Therefore, the inpatient setting may be a valuable site of initial counseling and referral for future potential provision of PrEP in the outpatient setting.

Disclosures
All Authors: No reported disclosures
60. Creation and Comparison of a Machine Learning Decision Tree and Traditional Risk Score to Predict Ceftriaxone Resistance in Cancer Patients with E. coli Bacteremia
Authors: Moc Courtney , Shropshire William , McDaneld Patrick , Shelburne Samuel A , Aitken Samuel L , Aitken Samuel L 
Published: December 2021

Abstract

Background
There are several clinical tools that have been developed to predict the likelihood of extended-spectrum β-lactamase producing Enterobacterales; however, the creation of these tools included few patients with cancer or otherwise immunosuppressed. The objectives of this retrospective cohort study were to develop a decision tree and traditional risk score to predict ceftriaxone resistance in cancer patients with Escherichia coli (E. coli) bacteremia as well as to compare the predictive accuracy between the tools.

Methods
Adults age ≥ 18 years old with E. coli bacteremia at The University of Texas MD Anderson Cancer Center from 1/2018 to 12/2019 were included. Isolates recovered within 1 week from the same patient were excluded. The decision tree was constructed using classification and regression tree analysis, with a minimum node size of 10. The risk score was created using a multivariable logistic regression model derived by using stepwise variable selection with backward elimination at level 0.2. The decision tree and risk score statistical metrics were compared.

Results
A total of 629 E. coli isolates were screened, of which 580 isolates met criteria. Ceftriaxone-resistant (CRO-R) E. coli accounted for 36% of isolates. The machine learning-derived decision tree included 5 predictors whereas the logistic regression-derived risk score included 7 predictors. The risk score cutoff point of ≥ 5 points demonstrated the most optimized overall classification accuracy. The positive predictive value of the decision tree was higher than that of the risk score (88% vs 74%, respectively), but the area under the receiver operating characteristic curve and model accuracy of the risk score was higher than that of the decision tree (0.85 vs 0.73 and 82% vs 74%, respectively).
Figure 1. Clinical Decision Tree

Table 1. Regression Model and Assigned Points for Clinical Risk Score

Table 2. Statistical Metrics of Clinical Decision Tree and Clinical Risk Score

Conclusion
The decision tree and risk score can be used to determine the likelihood of whether a cancer patient with E. coli bacteremia has a CRO-R infection. In both clinical tools, the strongest predictor was a history of CRO-R E. coli colonization or infection in the last 6 months. The decision tree was more user-friendly, has fewer variables, and has a better positive predictive value in comparison to the risk score. However, the risk score has a significantly better discrimination and model accuracy than that of the decision tree.

Disclosures
Samuel L. Aitken, PharmD, MPH, BCIDP, Melinta Therapeutoics (Individual(s) Involved: Self): Consultant, Grant/Research Support