bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of step-down oral antibiotic therapy for uncomplicated streptococcal bloodstream infections on clinical outcomes
Authors: Kang Amy , Beuttler Richard , Minejima Emi 
Published: January 2022

Background: Despite the severity and frequency of streptococcal bloodstream infections (BSIs), the effectiveness of oral definitive therapy remains unknown. The objective of this study was to evaluate the clinical outcomes of step-down oral antibiotics for the treatment of uncomplicated streptococcal BSIs. Methods: In this retrospective cohort study, adult patients admitted with uncomplicated streptococcal BSI between June 2015 and June 2017 were included. Patients were excluded if they received <48 h of antibiotic therapy; therapy was started >48 h after first positive culture; had complicated infections of endocarditis, bone and joint infections, or central nervous system infections; Pitt bacteremia score (PBS) ⩾ 4; or failed to respond to effective therapy necessitating continued intravenous (IV) therapy. Patients were grouped by receipt of step-down oral antibiotic therapy (PO group) versus continued IV therapy (IV group). Outcomes included hospital length of stay (LOS), 30-day recurrence of BSI, 30-day readmission, 30-day all-cause mortality, and catheter-related or drug-related adverse events (AEs). Results: Of 244 patients included, 40% received step-down oral therapy ( n = 98). Overall, the most common source of BSI was pneumonia (22%), followed by skin and soft tissue infections (SSTI) (18%). Severity of illness measured by intensive care unit (ICU) admission and PBS was similar. The IV group had significantly longer LOS [median 10 (interquartile range [IQR] = 5–21) versus 5 (4–6) days, p < 0.01] compared with the PO group. BSI recurrence, readmission, all-cause mortality within 30 days, and AEs were similar between the groups ( p = ns). Conclusion: In uncomplicated streptococcal BSI, patients treated with step-down oral antibiotic therapy had significantly shorter LOS compared with continued IV therapy without compromise of clinical outcomes.
Feeling and Learning: A Study of Students’ Emotions in the Sonography Classroom
Authors: Kurtz Abby 
Published: January 2022

Objective: The aim of this study was to explore the phenomenon of academic emotions experienced by sonography students. Materials and Methods: In this hermeneutic phenomenological study, in-depth, semi-structured phenomenological interviews were conducted to learn about participants’ emotional experiences while learning sonography. Thematic analysis was utilized in an effort to understand participants’ experiences with the phenomenon. Results: This study yielded the following interpretive themes: (1) the classroom emotional climate impacts students’ thoughts about learning sonography, (2) academic emotions can either boost or detract from students’ interest, motivation, and enthusiasm for the course material, and (3) relationships with their teachers matter to sonography students. Conclusion: An increased awareness of the interrelatedness of emotion and cognition in sonography education would benefit not only sonography educators and students but ultimately the patients whom those students will care for by improving the quality of education that students receive.
Hematopoietic stem cell transplantation for Wiskott-Aldrich syndrome: an EBMT Inborn Errors Working Party analysis
Authors: Albert Michael H. , Slatter Mary A. , Gennery Andrew R. , Güngör Tayfun , Bakunina Katerina , Markovitch Benyamin , Hazelaar Sheree , Sirait Tiarlan , Courteille Virginie , Aiuti Alessandro , Aleinikova Olga V. , Balashov Dmitry , Bernardo Maria Ester , Bodova Ivana , Bruno Benedicte , Cavazzana Marina , Chiesa Robert , Fischer Alain , Hauck Fabian , Ifversen Marianne , Kałwak Krzysztof , Klein Christoph , Kulagin Alexander , Kupesiz Alphan , Kuskonmaz Baris , Lindemans Caroline A. , Locatelli Franco , Lum Su Han , Maschan Alexey , Meisel Roland , Moshous Despina , Porta Fulvio , Sauer Martin G. , Sedlacek Petr , Schulz Ansgar , Suarez Felipe , Vallée Tanja C. , Winiarski Jacek H. , Zecca Marco , Neven Bénédicte , Veys Paul , Lankester Arjan C. 
Published: January 2022

Abstract
Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for patients affected by Wiskott-Aldrich syndrome (WAS). Reported HSCT outcomes have improved over time with respect to overall survival, but some studies have identified older age and HSCT from alternative donors as risk factors predicting poorer outcome. We analyzed 197 patients undergoing transplant at European Society for Blood and Marrow Transplantation centers between 2006 and 2017 who received conditioning as recommended by the Inborn Errors Working Party (IEWP): either busulfan (n = 103) or treosulfan (n = 94) combined with fludarabine ± thiotepa. After a median follow-up post-HSCT of 44.9 months, 176 patients were alive, resulting in a 3-year overall survival of 88.7% and chronic graft-versus-host disease (GVHD)-free survival (events include death, graft failure, and severe chronic GVHD) of 81.7%. Overall survival and chronic GVHD-free survival were not significantly affected by conditioning regimen (busulfan- vs treosulfan-based), donor type (matched sibling donor/matched family donor vs matched unrelated donor/mismatched unrelated donor vs mismatched family donor), or period of HSCT (2006-2013 vs 2014-2017). Patients aged &lt;5 years at HSCT had a significantly better overall survival. The overall cumulative incidences of grade III to IV acute GVHD and extensive/moderate/severe chronic GVHD were 6.6% and 2.1%, respectively. Patients receiving treosulfan-based conditioning had a higher incidence of graft failure and mixed donor chimerism and more frequently underwent secondary procedures (second HSCT, unconditioned stem cell boost, donor lymphocyte infusion, or splenectomy). In summary, HSCT for WAS with conditioning regimens currently recommended by IEWP results in excellent survival and low rates of GVHD, regardless of donor or stem cell source, but age ≥5 years remains a risk factor for overall survival.
ddRAD-seq reveals the genetic structure and detects signals of selection in Italian brown trout
Authors: Magris Gabriele , Marroni Fabio , D’Agaro Edo , Vischi Massimo , Chiabà Cristina , Scaglione Davide , Kijas James , Messina Maria , Tibaldi Emilio , Morgante Michele 
Published: January 2022

Abstract
Background
Brown trout is one of the most widespread fresh-water fish species in Europe. The evolutionary history of and phylogenetic relationships between brown trout populations are complex, and this is especially true for Italian populations, which are heavily influenced in different ways by stocking practices. The characterization of the genetic structure of Italian brown trout populations may give information on the risk of losing endemic Italian populations due to lack of genetic diversity or to admixture with stocking populations. The identification of signatures of selection, and the information deriving from dense genotyping data will help genotype-informed breeding programs. We used a ddRAD-seq approach to obtain more than 100,000 single nucleotide polymorphisms (SNPs), and to characterize the population structure and signatures of selection in 90 brown trout samples.

Results
Italian brown trout populations are genetically differentiated, although the stocking practices have introduced strong admixture in endemic Italian trout, especially with the Atlantic lineage. Most of the analysed populations showed high levels of kinship and inbreeding. We detected putative signatures of selection using different approaches, and investigated if the regions were enriched for functional categories. Several regions putatively under selection and characterized by a reduction in heterozygosity across all the studied populations are enriched for genes involved in the response to viral infections.

Conclusions
Our results, which show evidence of admixture with the Atlantic lineage (commonly used for stocking), confirm the need for controlling stocking practices, in order to avoid the erosion of the endemic gene pool; given the apparently high levels of kinship and inbreeding in local populations, our results also show the need to take action for increasing gene diversity. In addition, we used the genetically-distinct lineages to detect signatures of selection and we identified putative signatures of selection in several regions associated with resistance to infectious diseases. These constitute candidate regions for the study of resistance to infections in wild and farmed trout.
NanoBRET in C. elegans illuminates functional receptor interactions in real time
Authors: Groß Victoria Elisabeth , Gershkovich Miron Mikhailowitsch , Schöneberg Torsten , Kaiser Anette , Prömel Simone 
Published: January 2022

Abstract
Background
Protein-protein interactions form the basis of every organism and thus, investigating their dynamics, intracellular protein localization, trafficking and interactions of distinct proteins such as receptors and their ligand-binding are of general interest. Bioluminescence resonance energy transfer (BRET) is a powerful tool to investigate these aspects in vitro. Since in vitro approaches mostly neglect the more complex in vivo situation, we established BRET as an in vivo tool for studying protein interactions in the nematode C. elegans.

Results
We generated worms expressing NanoBRET sensors and elucidated the interaction of two ligand-G protein-coupled receptor (GPCR) pairs, the neuropeptide receptor NPR-11 and the Adhesion GPCR LAT-1. Furthermore, we adapted the enhanced bystander BRET technology to measure subcellular protein localization. Using this approach, we traced ligand-induced internalization of NPR-11 in vivo.

Conclusions
Our results indicate that in vivo NanoBRET is a tool to investigate specific protein interactions and localization in a physiological setting in real time in the living organism C. elegans.
Context dependency of nucleotide probabilities and variants in human DNA
Authors: Liang Yuhu , Grønbæk Christian , Fariselli Piero , Krogh Anders 
Published: January 2022

Abstract
Background
Genomic DNA has been shaped by mutational processes through evolution. The cellular machinery for error correction and repair has left its marks in the nucleotide composition along with structural and functional constraints. Therefore, the probability of observing a base in a certain position in the human genome is highly context-dependent.

Results
Here we develop context-dependent nucleotide models. We first investigate models of nucleotides conditioned on sequence context. We develop a bidirectional Markov model that use an average of the probability from a Markov model applied to both strands of the sequence and thus depends on up to 14 bases to each side of the nucleotide. We show how the genome predictability varies across different types of genomic regions. Surprisingly, this model can predict a base from its context with an average of more than 50% accuracy. For somatic variants we show a tendency towards higher probability for the variant base than for the reference base. Inspired by DNA substitution models, we develop a model of mutability that estimates a mutation matrix (called the alpha matrix) on top of the nucleotide distribution. The alpha matrix can be estimated from a much smaller context than the nucleotide model, but the final model will still depend on the full context of the nucleotide model. With the bidirectional Markov model of order 14 and an alpha matrix dependent on just one base to each side, we obtain a model that compares well with a model of mutability that estimates mutation probabilities directly conditioned on three nucleotides to each side. For somatic variants in particular, our model fits better than the simpler model. Interestingly, the model is not very sensitive to the size of the context for the alpha matrix.

Conclusions
Our study found strong context dependencies of nucleotides in the human genome. The best model uses a context of 14 nucleotides to each side. Based on these models, a substitution model was constructed that separates into the context model and a matrix dependent on a small context. The model fit somatic variants particularly well.
Comparative genomic analyses of Polymyxin-resistant Enterobacteriaceae strains from China
Authors: He Zhien , Yang Yongqiang , Li Wei , Ma Xiaoling , Zhang Changfeng , Zhang Jingxiang , Sun Baolin , Ding Tao , Tian Guo-bao 
Published: January 2022

Abstract
Background
Mobile colistin resistance like gene (mcr-like gene) is a new type of polymyxin resistance gene that can be horizontally transferred in the Enterobacteriaceae. This has brought great challenges to the treatment of multidrug-resistant Escherichia coli and K. pneumoniae.

Results
K. pneumoniae 16BU137 and E. coli 17MR471 were isolated from the bus and subway handrails in Guangzhou, China. K. pneumoniae 19PDR22 and KP20191015 were isolated from patients with urinary tract infection and severe pneumonia in Anhui, China. Sequence analysis indicated that the mcr-1.1 gene was present on the chromosome of E. coli 17MR471, and the gene was in the gene cassette containing pap2 and two copies of ISApl1.The mcr-1.1 was found in the putative IncX4 type plasmid p16BU137_mcr-1.1 of K. pneumoniae 16BU137, but ISApl1 was not found in its flanking sequence. Mcr-8 variants were found in the putative IncFIB/ IncFII plasmid pKP20191015_mcr-8 of K. pneumoniae KP20191015 and flanked by ISEcl1 and ISKpn26.

Conclusion
This study provides timely information on Enterobacteriaceae bacteria carrying mcr-like genes, and provides a reference for studying the spread of mcr-1 in China and globally.
Prevalence of Hepatitis B Virus infection and associated factors among female sex workers using respondent-driven sampling in Hawassa City, Southern Ethiopia
Authors: Daka Deresse , Hailemeskel Getahun , Fenta Demissie Assegu 
Published: January 2022

AbstractBackgroundFemale sex workers (FSWs) are a marginalized group notoriously having limited healthcare access and poor-quality care. Inevitably, they are vulnerable to sexually transmitted infections including hepatitis B virus. However; Hepatitis B virus infection is one of the most serious infections and major public health problem considered to be at soaring risk for transmission and acquisition of the infection. Hence, this study was aimed to assess the prevalence and associated factors of HBV infections among FSWs in southern Ethiopia.MethodsA cross-sectional study was conducted from November to February 2019 at Hawassa city in ISHDO confidential clinic among 383 FSWs. Respondent-drivenconsecutivesampling was used to select study participants using a standardized questionnaire. Blood sample was collected and viral surface antigen was detected using ELISA from separated serum. Data were entered to SPSS version 21.0. Descriptive and logistic regression analyses were used.ResultThe overall prevalence of FSWs who were tested for HBV using ELISA was 35(9.2%) (95% CI: 6.3–12.1). Among 381 FSWs 249(65.4%) were stayed for 2–5 years in sexual work and 240(63%) of them were used condom consistently during sexual practice. In multivariate logistic regression analysis, FSWs who didn’t use condom were six and two times more risk full to acquire HBV than those who used condom commonly (AOR = 6.38, CI 2.04–18.51) and condom breakage (AOR = 2.10, CI 1.95–4.65), during sexual practice respectively. Similarly, use of stimulants (AOR = 3.25, CI 1.59–18.63), previous history of STI (AOR = 2.15, CI 1.02–6.93), genital ulcer (AOR = 4.64, CI 1.31–11.35), number of sexual partners (AOR = 3.25, CI 1.59–7.47), sex during menses (AOR = 5.85, CI (1.29–21.44), sexual assault (AOR = 2.93, CI 1.23–9.01), sharp material sharing, (AOR = 4.98, CI 1.34–10.95) and history of abortion, (AOR = 2.46, CI 1.18, 12.19), were statistically associated with HBV infection. Factors such as age, residence, and alcohol consumption were not associated with HBV infection.ConclusionThe prevalence of HBV infection in this study was relatively high compared to the general population. Factors like sociodemographic, behavioral, and previous history-related information were associated with HBV infection shows the need for ongoing screening of high-risk population to inform planning for vaccination and preventive measures.
Development of a new serotyping ELISA for Toxoplasma gondii type II, type III and Africa 1 lineages using in silico peptide discovery methods, well categorized feline and human outbreak serum samples
Authors: Can Hüseyin , Aksoy Gökmen Ayşegül , Döşkaya Mert , Erkunt Alak Sedef , Değirmenci Döşkaya Aysu , Karakavuk Muhammet , Köseoğlu Ahmet Efe , Karakavuk Tuğba , Gül Ceren , Güvendi Mervenur , Gül Aytül , Gürüz Adnan Yüksel , Kaya Selçuk , Mercier Aurélien , Ün Cemal 
Published: January 2022

Abstract
Background
Discovery of new Toxoplasma gondii serotyping epitopes is important due to reports showing the influence of genotype on the severity of toxoplasmosis. In Turkey, genotypes belonging to type II, type III and Africa 1 lineages were mainly detected. The present study focused on to find out epitopes with high discriminative capacity to serotype these genotypes using well characterized strains isolated from Turkey.

Methods
To meet this objective, GRA6 and GRA7 genes were sequenced from strains belonging to the type II, III and Africa 1 lineages, and B cell epitopes inside these sequences were predicted by Bcepred and additional docking analysis was performed with B cell receptor. Based on these analyses, 22 peptides harboring lineage specific epitopes were synthesized. Then, the serotyping potency of these peptides was tested using peptide ELISA and well categorized serum samples collected from stray cats infected with genotypes of the different lineages type II (n:9), III (n:1) and Africa 1 (n:1). As a result of peptide-ELISA, a serotyping schema was constructed with peptides that show high discriminative capacity and this assay was validated by sera collected from humans after an outbreak (n:30) and mother/newborn pair sera (n:3). Later, the validated serotyping schema was used to serotype a larger group of human (n:38) and cat (n:24) sera.

Results
Among 22 peptides, GRA6II/c, GRA7III/d, and GRA6 Africa 1/b epitopes have shown discriminative capacity. During the validation of peptide-ELISA, the serotype of toxoplasmosis outbreak and mother/newborn cases were detected to be serotype II. Moreover, the analyses in a larger group showed that serotype II was prevalent in humans and stray cats.

Conclusions
Overall, the results showed that the serotyping schema could be successfully used to serotype T. gondii infections caused by type II, III and Africa 1 genotype.
Ceftazidime and cefepime antagonize 5-fluorouracil’s effect in colon cancer cells
Authors: Pfab Christina , Abgaryan Anush , Danzer Barbara , Mourtada Fatme , Ali Weaam , Gessner André , El-Najjar Nahed 
Published: January 2022

Abstract
Background
Drug-drug interaction (DDI), which can occur at the pharmacokinetics and/or the pharmacodynamics (PD) levels, can increase or decrease the therapeutic or adverse response of a drug itself or a combination of drugs. Cancer patients often receive, along their antineoplastic agents, antibiotics such as ß-lactams to treat or prevent infection. Despite the narrow therapeutic indices of antibiotics and antineoplastic agents, data about their potential interaction are insufficient. 5-fluorouracil (5-FU), widely used against colon cancer, is known for its toxicity and large intra- and inter- individual variability. Therefore, knowledge about its interaction with antibiotics is crucial.

Methods
In this study, we evaluated at the PD levels, against HCT-116 colon cancer cells, DDI between 5-FU and several ß-lactams (ampicillin, benzypenicillin, piperacillin, meropenem, flucloxacillin, ceftazidime (CFT), and cefepime (CFP)), widely used in intensive care units. All drugs were tested at clinically achieved concentrations. MTT assay was used to measure the metabolic activity of the cells. Cell cycle profile and apoptosis induction were monitored, in HCT-116 and DLD-1 cells, using propidium iodide staining and Caspase-3/7 activity assay. The uptake of CFT and CFP by the cells was measured using LC-MS/MS method.

Results
Our data indicate that despite their limited uptake by the cells, CFT and CFP (two cephalosporins) antagonized significantly 5-FU-induced S-phase arrest (DLD-1 cells) and apoptosis induction (HCT-116 cells). Remarkably, while CFP did not affect the proliferation of colon cancer cells, CFT inhibited, at clinically relevant concentrations, the proliferation of DLD-1 cells via apoptosis induction, as evidenced by an increase in caspase 3/7 activation. Unexpectedly, 5-FU also antagonized CFT’s induced cell death in DLD-1 cells.

Conclusion
This study shows that CFP and CFT have adverse effects on 5-FU’s action while CFT is a potent anticancer agent that inhibits DLD-1 cells by inducing apoptotic cell death. Further studies are needed to decipher the mechanism(s) responsible for CFT’s effects against colon cancer as well as the observed antagonism between CFT, CFP, and 5-FU with the ultimate aim of translating the findings to the clinical settings.
Number of negative lymph nodes with a positive impact on survival of stage III colon cancer; a retrospective observation study for right side and left side colon
Authors: Kuo Yi-Hung , You Jeng-Fu , Hung Hsin-Yuan , Chin Chih-Chien , Chiang Jy-Ming , Chang Chia-Hao 
Published: January 2022

Abstract
Background
The purpose was to examine the effect of negative lymph nodes (NLN) number on survival in stage III colon cancer. To reduce the interference of acute inflammation, we included patients with stage III colon cancer who had undergone elective surgery and excluded those who had tumor perforation, obstruction, ischemia, or massive tumor bleeding.

Methods
This retrospective cohort study included 2244 patients with stage III colon cancer between 1995 and 2016 at a single center. The effect of NLN on 5-year relapse-free survival (RFS), 5-year overall survival (OS), and comparison of multivariate factors was assessed according to tumor locations.

Results
The two optimal cutoff values of NLN for proximal and distal colon, namely 27 and 12, were determined by plotting the time-dependent receiver operating characteristic curve. Overall, 499 of 891 and 1020 of 1353 patients with right-side and left-side colon cancer, respectively, had high NLN. In right-side colon cancer, patients with high NLN (≥ 27) had superior OS (74.9% vs. 62.7%, P <  0.001) and RFS (75.0% vs. 61.9%, P <  0.001) than did those with low NLN. Moreover, in left-side colon cancer, patients with high NLN (≥12) experienced significantly superior OS (80.8% vs. 68.6%, P <  0.001) and RFS (77.3% vs. 66.2%, P <  0.001) than did those with low NLN. Among the different subgroups of stage III colon cancer, the high NLN group showed significantly superior RFS and OS in stage IIIB (RFS: 77.0% vs. 68.0%, P = 0.001; OS: 78.6% vs. 67.9%, P <  0.001) and IIIC (RFS: 58.2% vs. 44.1%, P = 0.001; OS: 65.7% vs. 51.1%, P <  0.001) colon cancer. However, in stage IIIA colon cancer, high NLN only showed survival benefit in OS (91.5% vs. 89.8%, P = 0.041). Multivariate analyses confirmed that high NLN, high carcinoembryonic antigen (≥ 5 ng/mL) level, and stage IIIC status are three independent prognostic factors in both the proximal and distal colon.

Conclusions
NLN is a crucial prognostic factor for stage III colon cancer in various tumor locations or in the subgroups of stage III disease. In advanced stage III colon cancer, the importance of NLN and its role in anti-cancer immune response could be highlighted.