bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolutionary history and introduction of SARS-CoV-2 Alpha VOC/B.1.1.7 in Pakistan through international travelers
Authors: Nasir Asghar , Bukhari Ali Raza , Trovão Nídia S , Thielen Peter M , Kanji Akbar , Mahmood Syed Faisal , Ghanchi Najia Karim , Ansar Zeeshan , Merritt Brian , Mehoke Thomas , Razzak Safina Abdul , Syed Muhammed Asif , Shaikh Suhail Raza , Wassan Mansoor , Aamir Uzma Bashir , Baele Guy , Rasmussen Zeba , Spiro David , Hasan Rumina , Hasan Zahra 
Published: March 2022

Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge, and their identification is important for the public health response to coronavirus disease 2019 (COVID-19). Genomic sequencing provides robust information but may not always be accessible, and therefore, mutation-based polymerase chain reaction (PCR) approaches can be used for rapid identification of known variants. International travelers arriving in Karachi between December 2020 and February 2021 were tested for SARS-CoV-2 by PCR. A subset of positive samples was tested for S-gene target failure (SGTF) on TaqPathTM COVID-19 (Thermo Fisher Scientific) and for mutations using the GSD NovaType SARS-CoV-2 (Eurofins Technologies) assays. Sequencing was conducted on the MinION platform (Oxford Nanopore Technologies). Bayesian phylogeographic inference was performed integrating the patients’ travel history information. Of the thirty-five COVID-19 cases screened, thirteen had isolates with SGTF. The travelers transmitted infection to sixty-eight contact cases. The B.1.1.7 lineage was confirmed through sequencing and PCR. The phylogenetic analysis of sequence data available for six cases included four B.1.1.7 strains and one B.1.36 and B.1.1.212 lineage isolate. Phylogeographic modeling estimated at least three independent B.1.1.7 introductions into Karachi, Pakistan, originating from the UK. B.1.1.212 and B.1.36 were inferred to be introduced either from the UK or the travelers’ layover location. We report the introduction of SARS-CoV-2 B.1.1.7 and other lineages in Pakistan by international travelers arriving via different flight routes. This highlights SARS-CoV-2 transmission through travel, importance of testing, and quarantine post-travel to prevent transmission of new strains, as well as recording detailed patients’ metadata. Such results help inform policies on restricting travel from destinations where new highly transmissible variants have emerged.
Rapid Multilocus Adaptation of Clonal Cabbage Leaf Curl Virus Populations toArabidopsis thaliana
Authors: Hoyer J. Steen , Wilkins Olivia W. , Munshi Aanandi , Wiese Emma , Dubey Divya , Renard Savannah , Mortensen Karoline Rosendal Hartø , Dye Anna E. , Carbone Ignazio , Duffy Siobain , Ascencio-Ibáñez José Trinidad 
Published: March 2022

Cabbage leaf curl virus (CabLCV) has a bipartite single-stranded DNA genome and infects the model plant Arabidopsis thaliana. CabLCV serves as a model for the genus Begomovirus, members of which cause tremendous crop losses worldwide. We have used CabLCV as a model for within-plant virus evolution by inoculating individual plants with infectious clones of either a wild-type or mutagenized version of the CabLCV genome. Consistent with previous reports, detrimental substitutions in the replication-associated ( Rep) gene were readily compensated for by direct reversion or alternative mutations. A surprising number of common mutations were detected elsewhere in both viral segments (DNA-A and DNA-B), indicating convergent evolution and suggesting that CabLCV may not be as well adapted to A. thaliana as commonly presumed. Consistent with this idea, a spontaneous coat protein variant consistently rose to high allele frequency in susceptible accession Columbia-0, at a higher rate than in hypersusceptible accession Sei-0. Numerous high-frequency mutations were also detected in a candidate Rep binding site in DNA-B. Our results reinforce the fact that spontaneous mutation of this type of virus occurs rapidly and can change the majority consensus sequence of a within-plant virus population in weeks.[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Legionella sainthelensi Pneumonia with Abdominal Symptoms as Prominent Manifestations: A Case Report
Authors: Yuan Xin , Meng Fanglin , Yu Xinting , Bai Changqing , Jia Rui , Meng Fanping , Wang Fu-sheng , Fu Junliang 
Published: March 2022

Abstract
Few studies have reported Legionella sainthelensi infection. This infection primarily presents with respiratory manifestations. Here, we report an immunocompromised patient with cavitary pneumonia caused by L. sainthelensi who mainly had abdominal symptoms. The timely administration of moxifloxacin provided clinical improvement and resolution of symptoms. To our knowledge, this is one of the rare cases of L. sainthelensi infection presenting uniquely with abdominal distension and liver function impairment but without obvious respiratory symptoms.
Current Advances of Innate and Adaptive Immunity in Acute-on-Chronic Hepatitis B Liver Failure
Authors: Wang Liyuan , Fan Yuchen 
Published: March 2022

Abstract
Acute-on-chronic hepatitis B liver failure (ACHBLF) is a term used to define the acute deterioration of liver function that occurs in patients with chronic hepatitis B virus infection or hepatitis B virus-related liver cirrhosis. The specific pathogenesis of ACHBLF is still not completely understood. Current research has shown that an intense systemic inflammation is involved in the development of acute-on-chronic liver failure (ACLF). Meanwhile, a subsequent immune paresis over the course of ACLF favors the development of infection and sepsis. Deregulation in both the innate and adaptive immunity is the notable feature of ACLF. The dysregulated immune responses play a crucial role in disease progression and potentially drive organ failure and mortality in ACHBLF. In this review, we highlight the current knowledge of innate and adaptive immune cells in ACHBLF.
Application of Dual-layer Spectral Detector Computed Tomography to Evaluate the Expression of Ki-67 in Colorectal Cancer
Authors: Wang Yu-Li , Zhang Han-Wen , Mo Yong-Qian , Zhong Hua , Liu Wei-Ming , Lei Yi , Lin Fan 
Published: March 2022

Background:
Compared with traditional computed tomography (CT), dual-layer spectral detector CT (SDCT) shows significant improvement in imaging soft tissues of the digestive tract. This work aimed to explore the application of SDCT to evaluate the expression of the molecular marker Ki-67 in colorectal cancer.

Methods:
We retrospectively analysed the imaging data of the SDCT (Philips Healthcare, IQon spectral CT) of 45 patients with colorectal cancer in our centre. We used Spearman’s test for the imaging parameters (reconstruction of 40, 70 keV, 100 keV virtual monoenergetic images (VMIs) and the slope of the HU attenuation plot (VMI-Slope) based on venous phase CT images, the arterial phase and venous phase iodine concentration (AP/VP-IC), and the effective atomic number (Z-effect)) and correlation analysis for the Ki-67 index. Multivariate logistic regression was used to eliminate confounding factors. We evaluated the expression level of Ki-67 and drew the ROC curve.

Results:
The 40 keV VMI, VMI-Slope and AP-IC were found to better reflect the Ki-67 index in patients with colorectal cancer with statistical significance. The 40 keV VMI (r=-0.612, p<0.001) and VMI-Slope (r=-0.523, p<0.001) were negatively correlated with the Ki-67 index, and AP-IC (r=0.378, p=0.010) was positively correlated with the Ki-67 index. The other indexes (p>0.05) were not statistically significant. The SDCT parameters demonstrated good performance, with AUCs of 0.785 for 40 keV VMI and 0.752 for AP-IC.

Conclusion:
The SDCT parameters 40 keV VMI and AP-IC can be used for preliminary evaluation of the Ki-67 index in colorectal cancer.
Association Between Sex Hormone Levels and Gut Microbiota Composition and Diversity—A Systematic Review
Authors: d’Afflitto Manfredi , Upadhyaya Advait , Green Alicia , Peiris Madusha 
Published: March 2022

Goals/Background:
Animal studies have highlighted how the microbiota acts in a sex-specific manner with sex hormones demonstrating an association with the composition and diversity of the microbiota. This systematic review aimed to gather the available scientific evidence to explore the association between sex hormones and gut microbiota composition and diversity, in humans.

Study:
Four bibliographic databases were searched in July 2020 using terms related to “microbiota,” “microflora,” “sex hormones,” “testosterone,” and “estrogen.” Human studies that investigated the correlation between sex hormones and the microbiota composition or diversity using next-generation sequencing were included.

Results:
A total of 10,468 records were screened with 13 studies included in this review. In healthy women, higher estrogen levels were found to be associated with a higher abundance of Bacteroidetes, a lower abundance of Firmicutes, the Ruminococcaceae family and increased diversity. In healthy men, raised testosterone levels positively correlated with Ruminococcus, Acinetobacter, and an increased microbial diversity. Escherichia and Shigella spp. were correlated with raised testosterone in healthy women whereas Ruminococcus spp. was negatively associated with elevated testosterone levels. Women with altered testosterone/estrogen profiles (such as in polycystic ovary syndrome), had a differing gut microbiota compared with healthy women.

Conclusions:
The findings gathered highlight an association between sex hormones and the gut microbiota composition/diversity and may contribute to the sex-based variations observed in disease pathogenesis. Factors such as age and medical conditions are implicated in the associations observed and should be accounted for in future studies. As the understanding of the complex symbiotic relationship between humans and their gut microbiota increases, microbiota modulation could be an attractive option for the prevention and treatment of gastrointestinal disorders.
Differences in Quality of Life and Emotional Well-being in Breast, Colon, and Lung Cancer Patients During Outpatient Adjuvant Chemotherapy
Authors: Ulibarri-Ochoa Ainhoa , Ruiz-de-Alegría Begoña , López-Vivanco Guillermo , García-Vivar Cristina , Iraurgi Ioseba 
Published: March 2022

Background
Adjuvant chemotherapy used at each cancer site may affect quality of life (QoL) and emotional well-being (affect) of cancer patients differently; however, these differences between groups have not been studied.

Objectives
The aim of this study was to assess differences in QoL and affect by cancer site at the start of outpatient adjuvant chemotherapy, whether QoL and affect change during this treatment, and whether adverse effects influence these variables.

Methods
A multicenter longitudinal descriptive study was conducted with 247 participants with breast, colon, or lung cancer at the beginning (T1) and end of treatment (T2). We used the SF-12 Health Survey, Positive and Negative Affect Scale, and an “ad hoc” adverse effects questionnaire.

Results
At the start of chemotherapy, the lung group had poorer Physical Component Summary and poorer positive and negative affect (P < .05) scores. In the end-of-treatment comparisons, breast and colon cancer patients’ status had worsened, whereas lung cancer patients had tended to stabilize, although they remained the most vulnerable. Adverse effect severity was significant for Physical Component Summary (r = −0.13, P = .035), with decreases in positive affect (r = −0.17, β = −.16) and increases in negative affect (r = 0.15, β = .14).

Conclusions
Changes in QoL and emotional state differ between groups, implying a need for varying levels of follow-up and emotional support. Patients with lung cancer seem particularly vulnerable.

Implications for Practice
Cancer nurses could strengthen the assessment of patients undergoing chemotherapy using more sensitive instruments such as the Positive and Negative Affect Scale and considering differences by cancer site, to provide care tailored to individual patient needs and preferences.
Naloxone prescribing practices in the Military Health System before and after policy implementation
Authors: Pakieser Jennifer , Peters Sidney , Tilley Laura C. , Costantino Ryan C. , Scott-Richardson Maya , Highland Krista B. 
Published: March 2022

Abstract

Introduction:
Despite public health campaigns, policies, and educational programs, naloxone prescription rates among people receiving opioids remains low. In June 2018, the U.S. Military Health System (MHS) released 2 policies to improve naloxone prescribing.

Objectives:
The objective of this study was to examine whether the policies resulted in increased naloxone coprescription rates for patients who met the criteria for 1 or more risk indicators (eg, long-term opioid therapy, benzodiazepine coprescription, morphine equivalent daily dose ≥50 mg, and elevated overdose risk score) at the time of opioid dispense.

Methods:
Prescription and risk indicator data from January 2017 to February 2021 were extracted from the MHS Data Repository. Naloxone coprescription rates from January 2017 to September 2018 were used to forecast prescribing rates from October 2018 to February 2021 overall and across risk indicators. Forecasted rates were compared with actual rates using Bayesian time series analyses.

Results:
The probability of receiving a naloxone coprescription was higher for patients whose opioid prescriber and pharmacy were both within military treatment facilities vs both within the purchased-care network. Bayesian time series results indicated that the number of patients who met the criteria for any risk indicator decreased throughout the study period. Naloxone prescribing rates increased across the study period from <1% to 20% and did not significantly differ from the forecasted rates across any and each risk indicator (adjusted P values all >0.05).

Conclusion:
Future analyses are needed to better understand naloxone prescribing practices and the impact of improvements to electronic health records, decision support tools, and policies.
Mandibular Distraction Osteogenesis in Robin Sequence Using Three-Dimensional Analysis and Planning
Authors: Pourtaheri Navid , Maniskas Seija , Chandler Ludmila , Steinbacher Derek M. 
Published: March 2022

Summary:
The optimal management of patients with Robin sequence may include neonatal mandibular distraction osteogenesis, which has been used to achieve excellent functional and aesthetic outcomes in appropriate patients. This article and video vignette depict the treatment of micrognathia and airway obstruction secondary to Robin sequence, demonstrating the planning and surgical approach of the senior author (D.M.S.) using mandibular distraction osteogenesis.
An Analysis of Serological Response and Infection Outcomes Following Oxford-AstraZeneca (AZD1222) and Pfizer-BioNTech (mRNA BNT162b2) SARS-CoV-2 Vaccines in Kidney and Kidney-pancreas Transplants
Authors: Asderakis Argiris , Khalid Usman , Koimtzis Georgios , Ponsford Mark J. , Szabo Laszlo , Chalklin Christopher , Bramhall Kathryn , Grant Leanne , Moat Stuart J. , Humphreys Ian R. , Jolles Stephen R. 
Published: March 2022

Background.
Severe acute respiratory syndrome coronavirus 2 is associated with high mortality among transplant recipients. Comparative data that define humoral responses to the Oxford-AstraZeneca (AZ) and BNT162b2 (Pfizer-BioNTech) vaccines are limited.

Methods.
We recruited 920 kidney transplant patients receiving at least 1 dose of severe acute respiratory syndrome coronavirus 2 vaccine, excluding patients with virus pre-exposure. Serological status was determined with the COVID-SeroKlir ELISA (Kantaro-EKF Diagnostics). Patients with a corrected antibody level of <0.7 AU/mL were considered seronegative.

Results.
Four hundred ninety-five AZ and 141 Pfizer patients had a sample analyzed after first dose and 593 after second dose (346 AZ versus 247 Pfizer). After first dose, 25.7% of patients seroconverted (26.6% AZ, 22.8% Pfizer). After second dose, 148 (42.8%) of AZ seroconverted compared with 130 (52.6%) of Pfizer (P = 0.02; hazard ratio, 1.48; 95% confidence interval, 1.07-2.06). When negative responders were excluded, Pfizer patients were shown to have significantly higher response than AZ patients (median 2.6 versus 1.78 AU/mL, P = 0.005).
Patients on mycophenolate had a reduced seroconversion rate (42.2% versus 61.4%; P < 0.001; hazard ratio, 2.17) and reduced antibody levels (0.47 versus 1.22 AU/mL, P = 0.001), and this effect was dose dependent (P = 0.05). Prednisolone reduced the seroconversion from 58.2% to 43.6% (P = 0.03) among Pfizer but not AZ recipients. Regression analysis showed that antibody levels were reduced by older age (P = 0.002), mycophenolate (P < 0.001), AZ vaccine (versus Pfizer, P = 0.001), and male gender (P = 0.02). Sixteen of 17 serious postvaccine infections occurred to patients who did not seroconvert.

Conclusions.
Both seroconversion and antibody levels are lower in AZ compared with Pfizer vaccinated recipients following 2 vaccine doses. Mycophenolate was associated with lower antibody responses in a dose-dependent manner. Serious postvaccine infections occurred among seronegative recipients.
Blue light exposure increases functional connectivity between dorsolateral prefrontal cortex and multiple cortical regions
Authors: Killgore William D.S. , Alkozei Anna , Vanuk John R. , Reign Deva , Grandner Michael A. , Dailey Natalie S. 
Published: March 2022

Objective
Blue light is a powerful environmental stimulus that can produce significant phase shifts in the circadian rhythm of melatonin and sleep propensity as well as acute effects on alertness of neurobehavioral performance. Here, we undertook an expansion and reanalysis of our previously published findings to examine the effect of acute blue light exposure on the strength of resting-state functional connectivity (rsFC) between a previously identified region of the left dorsolateral prefrontal cortex (DLPFC) and 106 cortical and subcortical regions.

Methods
Twenty-nine healthy adults (16 men and 13 women; age 18–32 years) completed a psychomotor vigilance test (PVT) before and after a single 30-min exposure to either blue (λ = 469 nm; n = 17) or amber wavelength (λ = 578 nm; n = 12) light, immediately followed by an rsFC scan.

Results
Compared with amber light, blue light exposure produced significantly greater functional connectivity between the left DLPFC seed region and 30 cortical and subcortical regions (P < 0.05; false discovery rate–corrected). Although neurobehavioral performance did not differ between light conditions, only those exposed to blue light showed a significant association between rsFC and sustained PVT performance. Better sustained PVT performance was associated with greater connectivity between the left DLPFC and regions associated with visuospatial awareness/motion detection (right temporal-occipital middle temporal gyrus) and memory (left hippocampus), as well as reduced connectivity in a circuit associated with cognitive rumination and distraction (left parahippocampal gyrus).

Conclusion
Findings suggest that blue-wavelength light may facilitate acute alertness and improved cognitive performance through enhanced rsFC between the left DLPFC and cortical regions associated with visuospatial awareness.
Boosting transformation in wheat by BBM-WUS
Authors: Zhou Ziru , Yang Yawen , Ai Guo , Zhao Miaomiao , Han Baozhu , Zhao Chunjie , Chen Yiqian , Zhang Yuwei , Pan Hong , Lan Caixia , Li Qiang , Xu Jieting , Yan Wenhao 
Published: March 2022

AbstractAgrobacterium–mediated transformation is a cost-effective and convenient way to introduce foreign genetic elements to plants. However, only limited protocols successfully generates transgenic plants with fielder, a spring wheat variety. Wheat transformation method with higher efficiency and without genotype restriction is heavily demanded. Here, a heat-shock protocol, independent of Japan Tobacco had been established. Transgenic plants can be obtained from immature embryo within only 60 days by this protocol. Morphogenic regulators Baby boom and Wuschel (BBM-WUS) was proved to promote transformation efficiency for five to six times in wheat when co-infiltrated with agrobacterium containing target construct. Notably, half of the transformants are BBM-WUS free and moreover, the BBM-WUS containing plants could be picked by florescent marker that was co-expressed with BBM-WUS. In conclusion, we managed to establish a new wheat transformation protocol with shorter duration than published protocol.
High life history diversity within a single genus of phytoplankton viruses
Authors: Lievens Eva J.P. , Agarkova Irina V. , Dunigan David D. , Van Etten James L. , Becks Lutz 
Published: March 2022

AbstractPhytoplankton viruses are key players in aquatic ecosystems, where they control algal populations and affect nutrient flow. The ecological impact and evolution of these viruses can be understood by studying their life history traits, but very little is known about the life history diversity of related viruses. We quantified the life cycle of 34 strains in the genusChlorovirus, which infects freshwater green algae. All chloroviral life history traits varied 5-to 75-fold across strains, in some cases rivaling the known trait range for all phytoplankton viruses. The trait variation affected viral growth rates but was not detectably constrained by life history trade-offs. This study represents the most in-depth characterization of algal viruses to date and raises the question whether all phytoplankton virus genera are equally diverse.
In vivo CRISPR screens reveal SCAF1 and USP15 as novel drivers of pancreatic cancer
Authors: Martinez Sebastien , Weber Ramona , Woo Tristan , Malik Ahmad , Geuenich Michael , Jang Gun Ho , Dervovic Dzana , Al-Zahrani Khalid N. , Tsai Ricky , Fodil Nassima , Gros Philippe , Sidhu Sachdev S , Gallinger Stephen , Neely G. Gregory , Campbell Kieran , Notta Faiyaz , Sendoel Ataman , Schramek Daniel 
Published: March 2022

AbstractFunctionally characterizing the genetic alterations that drive pancreatic cancer progression is a prerequisite for Precision Medicine. Here, we developed a somatic CRISPR/Cas9 mutagenesis screen to assess the transforming potential of 125 recurrently mutated ‘long-tail’ pancreatic cancer genes, which revealed USP15 and SCAF1 as novel and potent Pancreatic ductal adenocarcinoma PDAC tumor suppressors, with USP15 functioning in a haplo-insufficient manner. Mechanistically, we found that loss of USP15 leads to reduced inflammatory responses associated with TNFα, TGF-β and IL6 signaling and sensitizes pancreatic cancer cells to PARP inhibition and gemcitabine. Similarly, genetic ablation of SCAF1 reduced inflammatory responses linked to TNFα, TGF-β and mTOR signaling and increased sensitivity to PARP inhibition. Furthermore, we identified that loss of SCAF1 resulted in the formation of a truncated inactive USP15 isoform at the expense of full length USP15, functionally coupling SACF1 and USP15. Notably, USP15 and SCAF1 mutations or copy number losses are observed in 31% of PDAC patients. Together, our results demonstrate the utility of in vivo CRISPR to integrate human cancer genomics with mouse modeling to delineate novel cancer driver genes USP15 and SCAF1 such as with potential prognostic and therapeutic implications.