bluuebunny/crossref_metadata_2025_split huggingface dataset:
Semiannual Treatment of Albendazole Alone is Efficacious for Treatment of Lymphatic Filariasis: A Randomized Open-label Trial in Cote d’Ivoire
Authors: Ouattara Allassane F , Bjerum Catherine M , Aboulaye Méité , Kouadio Olivier , Marius Vanga K , Andersen Britt , Lew Daphne , Goss Charles W , Weil Gary J , Koudou Benjamin G , King Christopher L 
Published: February 2021

Abstract

Background
Ivermectin (IVM) plus albendazole (ALB), or IA, is widely used in mass drug administration (MDA) programs that aim to eliminate lymphatic filariasis (LF) in Africa. However, IVM can cause severe adverse events in persons with heavy Loa loa infections that are common in Central Africa. ALB is safe in loiasis, but more information is needed on its efficacy for LF. This study compared the efficacy and safety of 3 years of semiannual treatment with ALB to annual IA in persons with bancroftian filariasis.

Methods
Adults with Wuchereria bancrofti microfilaremia (Mf) were randomized to receive either 3 annual doses of IA (N = 52), 6 semiannual doses of ALB 400 mg (N = 45), or 6 semiannual doses of ALB 800 mg (N = 47). The primary outcome is amicrofilaremia at 36 months.

Results
IA was more effective for completely clearing Mf than ALB 400mg or ALB 800mg (79%, 95% confidence interval [CI]: 67–91; vs 48%, 95% CI: 32–66 and 57%, 95% CI: 41–73, respectively). Mean percentage reductions in Mf counts at 36 months relative to baseline tended to be greater after IA (98%, 95% CI: 88–100) than after ALB 400 mg (88%, 95% CI: 78–98) and ALB 800 mg (89%, 95% CI: 79–99) (P = .07 and P = .06, respectively). Adult worm nest numbers (assessed by ultrasound) were reduced in all treatment groups. Treatments were well tolerated.

Conclusions
Repeated semiannual treatment with ALB is macrofilaricidal for W. bancrofti and leads to sustained reductions in Mf counts. This is a safe and effective regimen that could be used as MDA to eliminate LF in areas where ivermectin cannot be used.

Clinical Trials Registration
NCT02974049
Comparable Outcomes of Short-Course and Prolonged-Course Therapy in Selected Cases of Methicillin-Susceptible Staphylococcus aureus Bacteremia: A Pooled Cohort Study
Authors: Thorlacius-Ussing Louise , Sandholdt Håkon , Nissen Jette , Rasmussen Jon , Skov Robert , Frimodt-Møller Niels , Dahl Knudsen Jenny , Østergaard Christian , Benfield Thomas 
Published: February 2021

Abstract

Background
The recommended duration of antimicrobial treatment for Staphylococcus aureus bacteremia (SAB) is a minimum of 14 days. We compared the clinical outcomes of patients receiving short-course (SC; 6–10 days), or prolonged-course (PC; 11–16 days) antibiotic therapy for low-risk methicillin-susceptible SAB (MS-SAB).

Methods
Adults with MS-SAB in 1995–2018 were included from 3 independent retrospective cohorts. Logistic regression models fitted with inverse probability of treatment weighting were used to assess the association between the primary outcome of 90-day mortality and treatment duration for the individual cohorts as well as a pooled cohort analysis.

Results
A total of 645, 219, and 141 patients with low-risk MS-SAB were included from cohorts I, II, and III. Median treatment duration in the 3 SC groups was 8 days (interquartile range [IQR], 7–10), 9 days (IQR, 8–10), and 8 days (IQR, 7–10). In the PC groups, patients received a median therapy of 14 days (IQR, 13–15), 14 days (IQR, 13–15), and 13 days (IQR, 12–15). No significant differences in 90-day mortality were observed between the SC and PC group in cohort I (odds ratio [OR], 0.85 [95% confidence interval {CI}, .49–1.41]), cohort II (OR, 1.24 [95% CI, .60–2.62]), or cohort III (OR, 1.15 [95% CI, .24–4.01]). This result was consistent in the pooled cohort analysis (OR, 1.05 [95% CI, .71–1.51]). Furthermore, duration of therapy was not associated with the risk of relapse.

Conclusions
In patients with low-risk MS-SAB, shorter courses of antimicrobial therapy yielded similar clinical outcomes as longer courses of therapy.
Propensity score-based analysis of long-term follow-up in patients supported with durable centrifugal left ventricular assist devices: the EUROMACS analysis
Authors: Potapov Evgenij V , Nersesian Gaik , Lewin Daniel , Özbaran Mustafa , de By Theo M M H , Stein Julia , Pya Yuri , Gummert Jan , Ramjankhan Faiz , Zembala Michael O , Damman Kevin , Carrel Thierry , Meyns Bart , Zimpfer Daniel , Netuka Ivan 
Published: February 2021

Abstract

OBJECTIVES
The HeartWare HVAD (HW) and the HeartMate3 (HM3) are presently the most commonly used continuous-flow left ventricular assist devices worldwide. We compared the outcomes of patients supported with either of these 2 devices based on data from the EUROMACS (European Registry for Patients with Mechanical Circulatory Support).

METHODS
A retrospective analysis of the survival and complications profile in propensity score-matched adult patients enrolled in the EUROMACS between 01 January 2016 and 01 September 2020 and supported with either an HW or HM3. Matching included demographic parameters, severity of cardiogenic shock and risk-modifying end-organ parameters that impact long-term survival. Survival on device and major postoperative adverse events were analysed.

RESULTS
Following 1:1 propensity score matching, each group consisted of 361 patients. Patients were well balanced (&lt;0.1 standardized mean difference). The median follow-up was similar in both groups [396 (interquartile range (IQR) 112–771) days for HW and 376 (IQR 100–816) days for HM3]. The 2-year survival was similar in both groups [HW: 61% 95% confidence interval (CI) (56–67%) vs HM3: 68% 95% CI (63–73%) (stratified hazard ratio for mortality: 1.13 95% CI (0.83–1.54), P = 0.435].The cumulative incidence for combined major adverse events and unexpected readmissions was similar in both groups [subdistribution hazard ratio (SHR) 1.0 (0.84–1.21), P = 0.96]. Patients in the HW group demonstrated a higher risk of device malfunction [SHR 2.44 (1.45–3.71), P &lt; 0.001], neurological dysfunction [SHR 1.29 (1.02–1.61), P = 0.032] and intracranial bleeding [SHR 1.76 (1.13–2.70), P = 0.012].

CONCLUSIONS
Mid-term survival in both groups was similar in a propensity-matched analysis. The risk of device malfunction, neurological dysfunction and intracranial bleeding was significantly higher in HW patients.
Pathogen Burden, Blood Biomarkers, and Functional Aging in Community-Dwelling Older Adults
Authors: Lu Yanxia , Tan Crystal Tze Ying , Gwee Xinyi , Yap Keng Bee , Fulop Tamas , Pan Fang , Larbi Anis , Ng Tze Pin 
Published: February 2021

Abstract

Background
Lifelong accumulation of latent or persistent or repeated infections may be a contributing factor to the deterioration of physical and cognitive function associated with functional aging, but the evidence is limited and the biological underpinnings are unclear.

Methods
We profiled the seropositivity for common viral, bacterial, and plasmodial pathogens of local importance in community-living older adults in 2 studies involving 745 older adults (mean age 67.0, SD: 7.7 years), and 142 older adults (mean age 72.7, SD: 8.3 years). Pathogen load was related to different sets of age-related physical and cognitive measures of functional aging and the Frailty Index (FI), and plasma levels of biomarkers of inflammation, innate and adaptive immunity, and other physiological functions.

Results
High pathogen load was associated with impaired gait speed (GS; p &lt; .015), functional mobility (performance-oriented mobility assessment [POMA]; p &lt; .029), cognitive function (Mini-Mental State Examination [MMSE]; p &lt; .05), and increased FI; p &lt; .05). High pathogen load was significantly associated with C3a complement activity (p &lt; .001), matrix metalloproteinase-7, macrophage inflammatory protein-1α (p &lt; .05), and monocyte chemoattractant protein 2 (p = .028). Blood biomarkers did not fully explain the observed association between pathogen load and functional aging measures.

Conclusions
This study provides novel evidence linking lifelong cumulated numbers of latent, persistent, or repeated infection to functional aging, plausibly via inflammatory and immune and other biological factors.
Invasive Aspergillosis After Influenza and Other Viral Respiratory Infections Among Intensive Care Unit Patients in a Commercially Insured Population in the United States, 2013–2018
Authors: Toda Mitsuru , Benedict Kaitlin , Jackson Brendan R 
Published: February 2021

Abstract
Influenza-associated aspergillosis (IAA) is an emerging phenomenon in intensive care unit patients with severe influenza. In a large US health insurance claims database, IAA was uncommon (0.3%) during 2013–2018. The low IAA frequency likely reflects underdiagnosis and differences in medical practices or epidemiologic differences.
Secukinumab as a potential trigger of inflammatory bowel disease in ankylosing spondylitis or psoriatic arthritis patients
Authors: Onac Ioana A , Clarke Benjamin D , Tacu Cristina , Lloyd Mark , Hajela Vijay , Batty Thomas , Thoroughgood Jamie , Smith Sandra , Irvine Hannah , Hill Diane , Baxter Grace , Horwood Natalie , Mahendrakar Suma , Rajak Rizwan , Griffith Sian , Kiely Patrick D W , Galloway James 
Published: February 2021

Abstract

Objective
Real-world secukinumab gastrointestinal-related adverse events (GIRAE) data during treatment for AS and PsA are lacking. We aimed to obtain this through baseline evaluation of pre-existing IBD rates and predictors of GIRAE.

Methods
Patient electronic and paper records commencing secukinumab from 10 UK hospitals between 2016 and 2019 were reviewed. GIRAE after initiation were defined as: definite [objective evidence of IBD (biopsy proven), clear temporal association, resolution of symptoms on drug withdrawal, no alternative explanation felt more likely], probable (as per definite, but without biopsy confirmation) or possible (gastrointestinal symptoms not fulfilling definite or probable criteria).

Results
Data for all 306 patients started on secukinumab were analysed: 124 (40.5%) AS and 182 (59.5%) PsA. Twenty-four of 306 (7.8%) experienced GIRAE after starting secukinumab. Amongst patients who developed GIRAE, four (1.3%) had definite, seven (2.3%) probable and 13 (4.2%) possible IBD. All definite cases were patients with AS and stopped secukinumab; two had pre-existing IBD and two (0.7%) were de novo cases of which one required surgical intervention. Seven patients (2.3%) had pre-existing diagnoses of IBD prior to initiation, of which five patients experienced GIRAE.

Conclusion
Absolute rates of new IBD in patients starting secukinumab are low. The majority of patients developing new GIRAE did not develop objective evidence of IBD or stop therapy. For patients with pre-existing IBD and AS the risk of GIRAE is much higher, and prescribing alternatives should be considered.
Risk Factors for Klebsiella infections among hospitalized patients with Pre-Existing Colonization
Authors: Rao Krishna , Patel Alieysa , Sun Yuang , Vornhagen Jay , Motyka Jonathan , Collingwood Abigail , Teodorescu Alexandra , Zhao Lili , Kaye Keith S. , Bachman Michael 
Published: February 2021

AbstractBackgroundKlebsiella commonly colonizes the intestinal tract of hospitalized patients and is a leading cause of healthcare-associated infections. Colonization is associated with subsequent infection, but the factors determining this progression are unclear.MethodsIntensive care and hematology/oncology patients were screened for Klebsiella colonization by rectal swab culture and monitored for infection for 90 days after a positive swab. Electronic medical records were analyzed for patient factors associated with subsequent infection, and variables of potential significance in bivariable analysis were used to build a final multivariable model. Concordance between colonizing and infecting isolates was assessed by wzi capsular gene sequencing.ResultsAmong 2087 hospital encounters from 1978 colonized patients, 90 cases of infection (4.3%) were identified. Mean time to infection was 20.6 ±24.69 (range 0-91, median 11.5) days. Of 86 typed cases, 68 unique wzi types were identified and 69 cases (80.2%) were colonized with an isolate of the same type prior to infection. Based on multivariable modeling, overall comorbidities, depression and low albumin level at the time of rectal swab were independently associated with subsequent Klebsiella infection.ConclusionsDespite the high diversity of colonizing strains of Klebsiella, there is high concordance with subsequent infecting isolates and progression to infection is relatively quick. Readily accessible data from the medical record could be used by clinicians to identify colonized patients at increased risk of subsequent Klebsiella infection.ImportanceKlebsiella is a leading cause of healthcare-associated infections. Patients who are intestinally colonized with Klebsiella are at significantly increased risk of subsequent infection, but only a subset of colonized patients progress to disease. Colonization offers a potential window of opportunity to intervene and prevent these infections, if the patients at greatest risk could be identified. To identify patient factors associated with infection in colonized patients, we studied 1978 colonized patients. We found that patients with a higher burden of underlying disease in general, depression in particular, and low albumin in a blood test were more likely to be a case of infection. However, these variables did not completely predict infection, suggesting that other host and microbial factors may also be important. The average time to infection was 3 weeks, suggesting that there is time to intervene and prevent Klebsiella infections in hospitalized patients.
TheParastagonospora nodorumnecrotrophic effector SnTox5 targets the wheat geneSnn5and facilitates entry into the leaf mesophyll
Authors: Kariyawasam Gayan K. , Richards Jonathan K. , Wyatt Nathan A. , Running Katherine , Xu Steven S. , Liu Zhaohui , Borowicz Pawel , Faris Justin D. , Friesen Timothy L. 
Published: February 2021

AbstractParastagonospora nodorum, causal agent of septoria nodorum blotch, is a destructive necrotrophic fungal pathogen of wheat.P. nodorumis known to secrete several necrotrophic effectors that target wheat susceptibility genes that trigger classical biotrophic resistance responses but resulting in susceptibility rather than resistance. SnTox5 targets the wheat susceptibility geneSnn5to induce necrosis. In this study, we used full genome sequences of 197P. nodorumisolates collected from the US and their disease phenotyping on theSnn5differential line LP29, to perform genome wide association study analysis to localize theSnTox5gene to chromosome 8 ofP. nodorum.SnTox5was validated using gene transformation and CRISPR-Cas9 based gene disruption.SnTox5encoded a small secreted protein with a 22 and 45 amino acid secretion signal and a pro sequence, respectively. TheSnTox5gene is under purifying selection in the Upper Midwest but under strong diversifying selection in the South/East regions of the US. Comparison of wild type and SnTox5-disrupted strains on wheat lines with and without the susceptibility targetSnn5showed that SnTox5 has two functions, 1) facilitating colonization of the mesophyll layer, and 2) targeting Snn5 to induce programmed cell death to provide cellular nutrient to complete its necrotrophic life cycle.
Evaluation of the growth performance, physiological traits, antioxidant indices, and heat shock protein 70 to dietary supplementation of stinging nettle (Urtica dioica) in broilers exposed to chronic heat stress
Authors: Farahani Mehrad Mirsaiidi , Hosseinian Seyedeh Alemeh 
Published: February 2021

AbstractHeat stress is known as one of the most prevalent environmental stressors in poultry production, which is associated with oxidative stress. Stinging nettle is a medicinal herb with strong antioxidant properties. The present study was conducted to evaluate the effects of dietary stinging nettle at two different levels (2% and 4%) on growth performance and oxidative stress indices of broilers exposed to chronic heat stress. On day 14, a total of 240 broiler chickens were randomly assigned to 6 treatment groups as follows: 1) NC: negative control; 2) HS: heat-stressed broiler; 3) HS-SN2: heat-stressed broiler fed by 2% dietary stinging nettle; 4) HS-SN4: heat-stressed broilers fed by 4% stinging nettle; 5) SN2: no heat-stressed broilers fed by 2% dietary stinging nettle; 6) SN4: no heat-stressed broilers fed by 4% dietary stinging nettle. Diet supplementation with stinging nettle was performed from days 14 to 35 and a chronic heat stress was induced from days 22 to 29. The growth performance and oxidative indices were evaluated on days 14, 21, 29, and 35. Rectal temperature and panting frequency were assessed on days 22, 25, and 29. As a result, weight gain and food intake decreased in the HS compared to the NC, and these parameters increased in the HS-SN2 and HS-SN4 compared to the HS (P<0.05). The HS, HS-SN2, and HS-SN4 groups had a significantly higher rectal temperature and panting frequency. The HS had the higher circulating MDA and HSP70, and lower T-AOC, SOD, and GSH-Px compared to the treatments. The HS-SN4 had a significantly lower MDA and HSP70, and higher T-AOC, GSH-Px, and SOD compared to the HS and HS-SN2. In conclusion, the addition of 4% stinging nettle powder to the broilers’ diet improved the oxidative status in heat-stressed birds. Furthermore, this herb could be utilized as a feed additive in poultry diet to improve bird’s health and defense mechanisms under stressful conditions.
Single-cell analysis identifies a key role forHhipin murine coronal suture development
Authors: Holmes Greg , Gonzalez-Reiche Ana S. , Saturne Madrikha , Zhou Xianxiao , Borges Ana C. , Shewale Bhavana , Zhang Bin , van Bakel Harm , Jabs Ethylin Wang 
Published: February 2021

AbstractCraniofacial development depends on proper formation and maintenance of sutures between adjacent bones of the skull. In sutures, bone growth occurs at the edge of each bone, and suture mesenchyme maintains the separation between them. We performed single-cell RNA-seq analyses of the embryonic, murine coronal suture. Analyzing replicate libraries at E16.5 and E18.5, we identified 14 cell populations. Seven populations at E16.5 and nine at E18.5 comprised the suture mesenchyme, osteogenic cells, and associated populations. Through an integrated analysis with bulk RNA-seq data, we found a distinct coronal suture mesenchyme population compared to other neurocranial sutures, marked by expression ofHhip, an inhibitor of hedgehog signaling. We found that at E18.5,Hhip-/-coronal osteogenic fronts are closely apposed and suture mesenchyme is depleted, demonstrating thatHhipis required for coronal suture development. Our transcriptomic approach provides a rich resource for insight into normal and abnormal development.
Chromatin and transcriptomic profiling uncover dysregulation of the Tip60 HAT/HDAC2 epigenomic landscape in the neurodegenerative brain
Authors: Beaver Mariah , Karisetty Bhanu Chandra , Zhang Haolin , Bhatnagar Akanksha , Armour Ellen , Parmar Visha , Brown Reshma , Xiang Merry , Elefant Felice 
Published: February 2021

ABSTRACTDisruption of histone acetylation mediated gene control is a critical step in Alzheimer’s Disease (AD), yet chromatin analysis of antagonistic histone acetyltransferases (HATs) and histone deacetylases (HDACs) causing these alterations remains uncharacterized. We report the first Tip60 HAT versus HDAC2 chromatin and transcriptional profiling study inDrosophilabrains that model early human AD. We find Tip60 and HDAC2 predominantly recruited to identical neuronal genes. Moreover, AD brains exhibit robust genome-wide early alterations that include enhanced HDAC2 and reduced Tip60 binding and transcriptional dysregulation. Orthologous human genes to co-Tip60/HDAC2Drosophilaneural targets exhibit conserved disruption patterns in AD patient hippocampi. Notably, we discovered distinct transcription factor (TF) binding sites within Tip60/HDAC2 co-peaks in neuronal genes, implicating them in co-enzyme recruitment. Increased Tip60 protects against transcriptional dysregulation and enhanced HDAC2 enrichment genome-wide. We advocate Tip60 HAT/HDAC2 mediated epigenetic neuronal gene disruption as a genome-wide initial causal event in AD.
A synthetic RNA-mediated evolution system in yeast
Authors: Jensen Emil D. , Laloux Marcos , Lehka Beata J. , Pedersen Lasse E. , Jakočiūnas Tadas , Jensen Michael K. , Keasling Jay D. 
Published: February 2021

AbstractLaboratory evolution is a powerful approach to search for genetic adaptations to new or improved phenotypes, yet either relies on labour-intensive human-guided iterative rounds of mutagenesis and selection, or prolonged adaptation regimes based on naturally evolving cell populations. Here we present CRISPR- and RNA-assistedin vivodirected evolution (CRAIDE) of genomic loci using evolving chimeric donor gRNAs continuously delivered from an error-prone T7 RNA polymerase, and directly introduced as RNA repair donors into genomic targets under either Cas9 or dCas9 guidance. We validate CRAIDE by evolving novel functional variants of an auxotrophic marker gene, and by conferring resistance to a toxic amino acid analogue in baker’s yeastSaccharomyces cerevisiaewith a mutation rate >3,000-fold higher compared to spontaneous native rate, thus enabling the first demonstrations ofin vivodelivery and information transfer from long evolving RNA donor templates into genomic context without the use ofin vitrosupplied and pre-programmed repair donors.
The scaffold-dependent function of RIPK1 in dendritic cells promotes injury-induced colitis
Authors: Moriwaki Kenta , Park Christa , Koyama Kazuha , Balaji Sakthi , Kita Kohei , Yagi Ryoko , Komazawa-Sakon Sachiko , Asuka Tatsuya , Nakano Hiroyasu , Kamada Yoshihiro , Miyoshi Eiji , Chan Francis K.M. 
Published: February 2021

AbstractReceptor interacting protein kinase 1 (RIPK1) is a cytosolic multidomain protein that controls cell life and death. While RIPK1 promotes cell death through its kinase activity, it also functions as a scaffold protein to promote cell survival by inhibiting FADD-caspase 8-dependent apoptosis and RIPK3-MLKL-dependent necroptosis. This pro-survival function is highlighted by excess cell death and a perinatal lethality inRipk1−/−mice. Recently, loss of function mutation ofRIPK1was found in patients with immunodeficiency and inflammatory bowel diseases. Hematopoietic stem cell transplantation restored not only immunodeficiency but also intestinal inflammatory pathology, indicating that RIPK1 in hematopoietic cells is critical to maintain intestinal immune homeostasis. Here, we generated dendritic cell (DC)-specificRipk1−/−mice in a genetic background with loss of RIPK1 kinase activity and found that the mice developed spontaneous colonic inflammation characterized by increased neutrophil infiltration. In addition, these mice were highly resistant to injury-induced colitis. The increased neutrophil infiltration in the colon and the resistance to colitis were restored by dual inactivation of RIPK3 and FADD, but not by inhibition of RIPK3, MLKL, or ZBP1 alone. Altogether, these results reveal a scaffold activity-dependent role of RIPK1 in protecting colonic DCs from apoptotic insults and maintenance of colonic immune homeostasis.