bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retrospective Analysis of Minimal Residual Disease Testing By High Throughput Immunosequencing Versus High Sensitivity Flow Cytometry in Multiple Myeloma
Authors: Khan Anwar , Pakasticali Nagehan , Fathalla Omar , Nishihori Taiga , Hussaini Mohammad O 
Published: November 2021

Abstract
Introduction:
Detection of minimal residual disease (MRD) is one of the strongest predictors of outcome in multiple myeloma (MM). Until recently, the most commonly available method to detect MRD in clinical practice has been high sensitivity flow cytometry (FC) which can detect MRD with at 10 -5 sensitivity. In recent years, next-generation sequencing (NGS) has become a viable method to assess the MRD in MM patients with a 10 -6 sensitivity. NGS appears to have some advantages over HC-FC by circumventing subjectivity of analysis. However, real-world comparison between these two methodologies in the literature is limited and is important to inform daily hematopathology and oncology ordering practices.
Methods:
We retrospectively identified all cases of MM with NGS MRD data from bone marrow specimens at the Moffitt Cancer Center and collated corresponding flow MRD data and clinical data (OS, patient demographics) electronically and via chart review.
10-color flow cytometry was performed on a Gallios System and analyzed on Kaluza (Beckman Coulter, IN). Two million events were collected on all cells. Validated lower limit of detection was at least 0.01%. Antibodies included CD28, CD81, CD56, CD138, CD319, CD20, CD19, CD117, CD38, CD45, CD27, CD200 (BD, Biolegend, Beckman Coulter).
clonoSEQ ® (Adaptive Biotechnologies, Seattle, WA) testing was performed which uses multiplex polymerase chain reaction (PCR) and NGS to identify, characterize, and monitor clonotypes of immunoglobulin (Ig) IgH (V-J), IgH (D-J), IgK, and IgL receptor gene sequences, and translocated BCL1/IgH (J) and BCL2/IgH (J) sequences
Statistical analysis was performed by Spearman correlation coefficient and Kaplan-Meier analysis.
Results:
192 samples from 122 unique patients were identified that had both NGS and FC data performed on the same sample. FC+ values ranged from 1x10 -7 to 0.39. NGS+ values ranged from 2.3 x 10 -7 to 0.15. Spearman correlation coefficient showed moderate concordance between NGS and FC at r=0.67 (p&lt;0.001). Six samples were positive by FC (mean tumor burden (MTB)= 0.0007) but missed by NGS; whereas 59 samples were positive by NGS (MTB= 0.002) but missed by flow cytometry. Two cases by FC were equivocal and these were both definitively designated as MRD+ by NGS. Overall survival was worse for MRD+ (by NGS or FC) vs MRD(-) (Figure 1).
Conclusion:
Our study confirms the importance of MRD detection in MM and shows the robust utility of NGS for MRD detection in routine hematopathology practice. While both FC and NGS are complementary given that each can potentially detect MRD missed by another method, the data supports the increased sensitivity of NGS over FC.
Figure 1 Figure 1.

Disclosures
Nishihori: Novartis: Research Funding; Karyopharm: Research Funding. Hussaini: Stemeline Therapeutics: Honoraria.
Rates of Neutropenic Fever in Patients with Hematologic Malignant Diseases with Central Venous Access
Authors: Abbagoni Sujith , Malik Sarah , Fox Ashley D , Mian Mohammad A. H. , Anwar Tahsin , Bradshaw Danielle , Bryan Locke J. , Jillella Anand P , Kolhe Ravindra , Savage Natasha M. , Padala Sandeep , Kota Vamsi 
Published: November 2021

Abstract
Background: Patients who are diagnosed with hematologic malignant diseases (HMD) almost invariably receive placement of central venous catheters (CVCs), whether temporary or permanent. These catheters are used for administration of various chemotherapies, antibiotics and even nutrition. Although the patients with HMD are immunocompromised, prophylactic use of antibiotics among these patients, especially related to CVC placement, remains controversial. This retrospective analysis evaluates the rates of development of neutropenic fever in patients with HMD with CVCs receiving prophylactic antibiotics.
Methods: Data were collected retrospectively in a cohort of 268 patients with HMD who received treatment at our academic institution between 2002 to 2019. Demographic and other related data was abstracted and descriptive analysis was performed using Epi-Info - 7 software.
Results: Of the 268 patients with HMD, 175 patients (65.3%) received prophylactic antibiotics and among these patients, 180 (67.2%) had a permanent CVC and 109 (40.7%) had a temporary CVC. Comparatively, 93 patients (34.7%) did not receive prophylactic antibiotics and among these individuals, 64 (68.8%) had a permanent CVC and 34 (36.6%) had a temporary CVC. In patients with a permanent central line, 84.3% of patients receiving prophylactic antibiotics developed neutropenic fever while 85% of those who did not receive prophylactic antibiotic also developed neutropenic fever. Among the individuals with a temporary CVC, 79.7% of patients receiving prophylactic antibiotics developed neutropenic fever and 65.4% of patients who were not receiving prophylactic antibiotics also developed neutropenic fever. None of the differences were statistically significant (p=0.8990 and p=0.1547 respectively).
Conclusion: In this cohort of HMD patients, the rate of neutropenic fever development in patients with central venous access receiving prophylactic antibiotic was not significantly different compared to the rate of neutropenic fever development in patients with central venous access who did not receive any prophylactic antibiotic. This data suggests that there does not appear to be a significant clinical utility for prophylactic antibiotics in the prevention of neutropenic fever in patients with HMD who have central venous catheters in place. Further studies analyzing the impact of prophylactic antibiotics on true infections as an etiology for neutropenic fevers in patients with HMD and central venous catheters is warranted.

Disclosures
No relevant conflicts of interest to declare.
A Novel Type V CRISPR System with Potential for Genome Editing in the Liver
Authors: Cost Gregory J. , Temoche-Diaz Morayma , Mei Janet , Butterfield Cristina N. , Brown Christopher T. , Brooks Alan R 
Published: November 2021

Abstract
RNA guided CRISPR genome editing systems can make specific changes to the genomes of mammalian cells and have the potential to treat a range of diseases including those that can be addressed by editing hepatocytes. Attempts to edit the liver in vivo have relied almost exclusively on the Cas9 nucleases derived from the bacteria S treptococcus pyogenes or Staphylococcus aureus to which humans are commonly exposed. Pre-existing immunity to both these proteins has been reported in humans which raises concerns about their in vivo application. In silico analysis of a large metagenomics database followed by testing in mammalian cells in culture identified MG29-1, a novel CRISPR system which is a member of the Type V family but exhibits only 41 % amino acid identity to Francisella tularensis Cas12a/cpf1. MG29-1 is a 1280 amino acid RNA programmable nuclease that utilizes a single guide RNA comprised of a 22 nucleotide (nt) constant region and a 20 to 25 nt spacer, recognizes the PAM KTTN (predicted frequency 1 in 16 bp) and generates staggered cuts. MG29-1 was derived from a sample taken from a hydrothermal vent and it is therefore unlikely that humans will have developed pre-existing immunity to this protein. A screen for sgRNA targeting serum albumin in the mouse liver cell line Hepa1-6 identified 6 guides that generated more than 80% INDELS. The MG29-1 system was optimized for in vivo delivery by screening chemical modifications to the guide that improve stability in mammalian cell lysates while retaining or improving editing activity. Two lead guide chemistries were evaluated in mice using MG29-1 mRNA and sgRNA packaged in lipid nanoparticles (LNP). Three days after a single IV administration on-target editing was evaluated in the liver by Sanger sequencing. The sgRNA that was the most stable in the in vitro assay generated INDELS that ranged from 20 to 25% while a sgRNA with lower in vitro stability failed to generate detectable INDELs. The short sgRNA and small protein size compared to spCas9 makes MG29-1 an attractive alternative to spCas9 for in vivo editing applications. Evaluation of the potential of MG29-1 to perform gene knockouts and gene additions via non-homologous end joining is ongoing.

Disclosures
No relevant conflicts of interest to declare.
Resolvin T-series reduce neutrophil extracellular traps
Authors: Chiang Nan , Sakuma Miyuki , Rodriguez Ana R. , Spur Bernd W. , Irimia Daniel , Serhan Charles N. 
Published: November 2021

Abstract
The newly identified 13-series (T-series) resolvins (RvTs) regulate phagocyte functions and accelerate resolution of infectious inflammation. Because severe acute respiratory syndrome coronavirus 2 elicits uncontrolled inflammation involving neutrophil extracellular traps (NETs), we tested whether stereochemically defined RvTs regulate NET formation. Using microfluidic devices capturing NETs in phorbol 12-myristate 13-acetate–stimulated human whole blood, the RvTs (RvT1-RvT4; 2.5 nM each) potently reduced NETs. With interleukin-1β–stimulated human neutrophils, each RvT dose and time dependently decreased NETosis, conveying ∼50% potencies at 10 nM, compared with a known NETosis inhibitor (10 μM). In a murine Staphylococcus aureus infection, RvTs (50 ng each) limited neutrophil infiltration, bacterial titers, and NETs. In addition, each RvT enhanced NET uptake by human macrophages; RvT2 was the most potent of the four RvTs, giving a &gt;50% increase in NET-phagocytosis. As part of the intracellular signaling mechanism, RvT2 increased cyclic adenosine monophosphate and phospho–AMP-activated protein kinase (AMPK) within human macrophages, and RvT2-stimulated NET uptake was abolished by protein kinase A and AMPK inhibition. RvT2 also stimulated NET clearance by mouse macrophages in vivo. Together, these results provide evidence for novel pro-resolving functions of RvTs, namely reducing NETosis and enhancing macrophage NET clearance via a cyclic adenosine monophosphate–protein kinase A–AMPK axis. Thus, RvTs open opportunities for regulating NET-mediated collateral tissue damage during infection as well as monitoring NETs.
Spliceator: multi-species splice site prediction using convolutional neural networks
Authors: Scalzitti Nicolas , Kress Arnaud , Orhand Romain , Weber Thomas , Moulinier Luc , Jeannin-Girardon Anne , Collet Pierre , Poch Olivier , Thompson Julie D. 
Published: November 2021

Abstract
Background
Ab initio prediction of splice sites is an essential step in eukaryotic genome annotation. Recent predictors have exploited Deep Learning algorithms and reliable gene structures from model organisms. However, Deep Learning methods for non-model organisms are lacking.

Results
We developed Spliceator to predict splice sites in a wide range of species, including model and non-model organisms. Spliceator uses a convolutional neural network and is trained on carefully validated data from over 100 organisms. We show that Spliceator achieves consistently high accuracy (89–92%) compared to existing methods on independent benchmarks from human, fish, fly, worm, plant and protist organisms.

Conclusions
Spliceator is a new Deep Learning method trained on high-quality data, which can be used to predict splice sites in diverse organisms, ranging from human to protists, with consistently high accuracy.
Transcriptome dynamics in developing testes of domestic cats and impact of age on tissue resilience to cryopreservation
Authors: Amelkina Olga , Silva Andreia M. da , Silva Alexandre R. , Comizzoli Pierre 
Published: November 2021

Abstract
Background
Fundamental knowledge of cellular and molecular mechanisms in developing testicular tissues is critical to better understand gonadal biology and responses to non-physiological conditions. The objective of our study was to (1) analyze transcriptome dynamics in developing testis of the domestic cat and (2) characterize age effects on the initial response of the tissue to vitrification. Tissues from adult and juvenile cats were processed for histology, DNA integrity, and RNA sequencing analyses before and after vitrification.

Results
Transcriptomic findings enabled to further characterize juvenile period, distinguishing between early and late juvenile tissues. Changes in gene expression and functional pathways were extensive from early to late juvenile to adult development stages. Additionally, tissues from juvenile animals were more resilient to vitrification compared to adult counterparts, with early juvenile sample responding the least to vitrification and late juvenile sample response being closest to adult tissues.

Conclusions
This is the first study reporting comprehensive datasets on transcriptomic dynamic coupled with structural analysis of the cat testis according to the age and exposure to cryopreservation. It provides a comprehensive network of functional terms and pathways that are affected by age in the domestic cat and are either enriched in adult or juvenile testicular tissues.
Risk of severe COVID-19 and mortality in patients with established chronic liver disease: a nationwide matched cohort study
Authors: Simon Tracey G. , Hagström Hannes , Sharma Rajani , Söderling Jonas , Roelstraete Bjorn , Larsson Emma , Ludvigsson Jonas F. 
Published: November 2021

Abstract
Background and aims
Some, but not all, prior studies have suggested that patients with chronic liver disease are at increased risk of contracting COVID-19 and developing more severe disease. However, nationwide data are lacking from well-phenotyped cohorts with liver histology and comparisons to matched general population controls.

Methods
We conducted a nationwide cohort study of all Swedish adults with chronic liver disease (CLD) confirmed by liver biopsy between 1966 and 2017 (n = 42,320), who were alive on February 1, 2020. CLD cases were matched to ≤ 5 population comparators by age, sex, calendar year and county (n = 182,147). Using Cox regression, we estimated multivariable-adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for COVID-19 hospitalization and severe COVID-19 (intensive care admission or death due to COVID-19).

Results
Between February 1 and July 31, 2020, 161 (0.38%) CLD patients and 435 (0.24%) general population controls were hospitalized with COVID-19 (aHR = 1.36, 95% CI = 1.11–1.66), while 65 (0.15%) CLD patients and 191 (0.10%) controls developed severe COVID-19 (aHR = 1.08, 95% CI = 0.79–1.48). Results were similar in patients with CLD due to alcohol use, nonalcoholic fatty liver disease, viral hepatitis, autoimmune hepatitis, and other etiologies. Among patients with cirrhosis (n = 2549), the aHRs for COVID-19 hospitalization and for severe COVID-19 were 1.08 (95% CI 0.48–2.40) and 1.23 (95% CI = 0.37–4.04), respectively, compared to controls. Moreover, among all patients diagnosed with COVID-19, the presence of underlying CLD was not associated with increased mortality (aHR = 0.85, 95% CI = 0.61–1.19).

Conclusions
In this nationwide cohort, patients with CLD had a higher risk of hospitalization for COVID-19 compared to the general population, but they did not have an increased risk of developing severe COVID-19.
Community-level educational attainment and dementia: a 6-year longitudinal multilevel study in Japan
Authors: Takasugi Tomo , Tsuji Taishi , Hanazato Masamichi , Miyaguni Yasuhiro , Ojima Toshiyuki , Kondo Katsunori 
Published: November 2021

Abstract
Background
As the understanding of the association between community-level education and dementia is insufficient, this study examined the contextual association of community-level prevalence of low educational attainment on the risk of dementia incidence. With this study, we further explored the potential differences in the aforementioned associations for urban and non-urban areas.

Methods
We analyzed 6 years of prospective cohort data from the Japan Gerontological Evaluation Study, beginning with the baseline data collected between 2010 and 2012, for 51,186 physically and cognitively independent individuals aged ≥65 years (23,785 men and 27,401 women) from 346 communities in 16 municipalities across 7 prefectures. We assessed dementia incidence using available data from the long-term care insurance system in Japan. We dichotomized education years as ≤9 and ≥ 10 years and aggregated individual-level educational attainment as a community-level independent variable. Model 1 covariates were age and sex. Income, residential years, disease, alcohol, smoking, social isolation, and population density were added in Model 2. We conducted multiple imputation to address the missing data. We performed a two-level (community and individual) survival analysis to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results
The results indicate that the cumulative incidence of dementia during the follow-up period was 10.6%. The mean proportion with educational attainment of ≤9 years was 40.8% (range: 5.1–87.3%). Low community-level educational attainment was significantly associated with higher dementia incidence (HR: 1.04; 95% CI: 1.01–1.07), estimated by 10 percentage points of low educational attainment after adjusting for individual-level educational years and covariates. While the association was significant in non-urban areas (HR: 1.07; 1.02–1.13), there was no association in urban areas (HR: 1.03; 0.99–1.06).

Conclusions
Older people living in communities with low educational attainment among their age demographic develop dementia more often compared with those living in areas with high educational attainment after adjusting for individual-level educational attainment and covariates; the association was pronounced in non-urban areas. Securing education for adolescents as a life course and population approach could thus be crucial in preventing dementia later in life among older people living in non-urban areas.
Spectrum of antibiotic resistance in UTI caused by Escherichia coli among HIV-infected patients in Uganda: a cross-sectional study
Authors: Abongomera George , Koller Maurice , Musaazi Joseph , Lamorde Mohammed , Kaelin Marisa , Tasimwa Hannington B. , Eberhard Nadia , Hongler Jan , Haller Sabine , Kambugu Andrew , Castelnuovo Barbara , Fehr Jan 
Published: November 2021

Abstract
Background
Antimicrobial drug resistance is one of the top ten threats to global health according to the World Health Organization. Urinary tract infections (UTIs) are among the most common bacterial infections and main reason for antibiotic prescription. The incidence of UTIs appears to be high among people living with HIV. We sought to determine the most common UTI pathogens among HIV infected patients and evaluate their susceptibility towards antibiotics.

Methods
We performed a cross-sectional study among HIV-infected patients aged ≥ 18 years presenting at an HIV care specialized clinic with symptoms suggestive of a urethritis. Urine cultures were subjected to antibiotic susceptibility testing according to Clinical Laboratory Standards Institute. The data was analyzed using STATA, we performed Pearson’s Chi-square and Fisher’s exact tests to compare differences between proportions.

Results
Out of the 200 patients, 123 (62%) were female. The median age was 41.9 years (IQR 34.7–49.3). Only 32 (16%) urine cultures showed bacterial growth. Escherichia coli was the most commonly isolated uropathogen (72%), followed by Klebsiella pneumoniae (9%). E. coli was completely resistant to cotrimoxazole and ampicillin; resistance to ciprofloxacin and ceftriaxone was 44% and 35% respectively; 9% to gentamicin; no resistance detected to nitrofurantoin and imipenem.

Conclusions
Our findings are congruent with the Uganda national clinical guidelines which recommends nitrofurantoin as the first line antibiotic for uncomplicated UTI. Significant ciprofloxacin and ceftriaxone resistance was detected. In the era of emerging antibiotic resistance, understanding the local susceptibilities among sub-populations such as HIV infected patients is crucial. Further investigation is needed to address reasons for the low bacterial growth rate observed in the urine cultures.
Stent encrustation or fragmentation? A case report of post stent removal encrustation in postpartum woman and literature review
Authors: Ye Zhaohua , Mi Qiwu , Huang Renzhao 
Published: November 2021

Abstract
Background
Ureteral stents are commonly used in the field of urology to relieve ureteral obstruction. However, complications relating to ureteral stent use, such as encrustation continue to occur, especially with prolonged indwell time.

Case presentation
Here we present a 37-year-old postpartum woman with a foreign body in her bladder after removing a ureteral stent 1 month before. She insisted that the foreign body was the fragment of stent and asked for medical malpractice indemnity payments while the surgeon of her insisted that the stent was intact during the procedure. Finally, the foreign body was confirmed as an encrustation by cystoscopy and the patient received 10,000 yuan ($ 1500) as indemnity payments after encrustation removal.

Conclusion
In the absence of guidelines, stent indwelling time vary with centers’ habits, stent materials and patient’s education. Early detection of stent encrustation and timely removal of the encrusted stent are still the best way to avoid stent retention. Violent stent removal is of danger and not recommended in any case.