bluuebunny/crossref_metadata_2025_split huggingface dataset:
Platelet count patterns and patient outcomes in sepsis at a tertiary care center
Authors: Al Saleh Khalid , AlQahtani Rakan M. 
Published: May 2021

Abstract
Acute physiology and chronic health evaluation II (APACHE-II) scoring system is used to classify disease severity of patients in the intensive care unit. However, several limitations render the scoring system inadequate in identifying risk factors associated with outcomes. Little is known about the association of platelet count patterns, and the timing of platelet count and other hematologic parameters in predicting mortality in patients with sepsis.
This retrospective observational study included 205 septic shock patients, with an overall mortality of 47.8%, enrolled at a tertiary care hospital in Riyadh, Kingdom of Saudi Arabia between 2018 and 2020. Bivariate and multivariate regression analyses were used to identify hematologic risk factors associated with mortality. We used the bivariate Pearson Correlation test to determine correlations between the tested variables and APACHE-II score.
Two platelet count patterns emerged: patients with a decline in platelet count after admission (group A pattern, 93.7%) and those with their lowest platelet count at admission (group B pattern, 6.3%). The lowest mean platelet count was significantly lower in nonsurvivors (105.62 ± 10.67 × 103/μL) than in survivors (185.52 ± 10.81 × 103/μL), P < .001. Bivariate Pearson correlation revealed that the lowest platelet count and platelet count decline were significantly correlated with APACHE-II score (r = −0.250, P < .01), (r = 0.326, P < .001), respectively. In multiple logistic regression analysis, the independent mortality risk factors were degree of platelet count decline in group A (odds ratio, 1.028 [95% confidence interval: 1.012–1.045], P = .001) and platelet pattern in group B (odds ratio, 6.901 [95% confidence interval: 1.446–32.932], P = .015). The patterns, values, subsets, and ratios of white blood cell count were not significantly associated with mortality.
Nadir platelet count and timing, and degree of platelet count decline are useful markers to predict mortality in early septic shock. Therefore, platelet count patterns might enhance the performance of severity scoring systems in the intensive care unit.
Ectopic tooth in maxillary sinus compressing the nasolacrimal canal
Authors: Yang Peng , Liang Hao , Zou Bo , Liu Jianlin , Yuan Daoying , Meng Zhen , Xu Kai 
Published: May 2021

Abstract

Rationale:
Ectopic tooth is tooth erupting out of normal anatomical position. Ectopic tooth can occur in different positions, such as maxillary sinus and nasal cavity. In this article, we present a rare case of an ectopic tooth with a dentigerous cyst in the maxillary sinus compressing the nasolacrimal canal.

Patient concerns:
An 8-year-old girl presented with a 2-month history of spontaneous lacrimation in her right eye. When she wept, more tear shed from her right eye than that from the left one. Computed tomographic (CT) imaging showed a huge low-density image containing a tooth in the maxillary sinus in her right maxilla; the right nasolacrimal canal vanished due to the compression of the ectopic tooth.

Diagnoses:
Ectopic tooth with dentigerous cyst of right maxilla, and obstruction of nasolacrimal duct

Interventions:
The patient underwent nasal endoscopic maxillary sinus cystectomy.

Outcomes:
The patient recovered well after cystectomy and has been symptom-free.

Lessons:
The unique finding is that this is the first report about ectopic tooth compressing the nasolacrimal canal and inducing spontaneous lacrimation. Treatment: aspect: surgery under endoscope is a minimally invasive approach to ectopic tooth.
Prognostic value of red blood cell distribution width in patients with acute pulmonary embolism
Authors: Liao Ye , Yang Chunsheng , Bakeer Banu 
Published: May 2021

Abstract

Background:
Prior reports have suggested that the red blood cell distribution width (RDW) parameter could be measured as a prognostic indicator in pulmonary embolism (PE) patients, thereby helping to guide their care. However, no systematic analyses on this topic have been completed to date, and the exact relationship between RDW and PE remains to be fully clarified. We will therefore conduct a systematic literature review with the goal of defining the correlation between RDW and mortality in acute PE cases.

Methods:
The EMBASE, Web of Knowledge, PubMed, ClinicalTrials.gov, and Cochrane Library databases will be searched for all relevant studies published from inception through March 2021 using the following search strategy: (“red blood cell distribution width”) AND (“pulmonary embolism”). Two authors will independently identify eligible studies and extract data. The Q and I
2 statistics will be used to judge heterogeneity among studies.

Results:
This study will establish the relative efficacy of RDW as a metric for predicting PE patient mortality.

Conclusions:
This study will offer a reliable, evidence-based foundation for the clinical utilization of RDW as a tool for gauging mortality risk in acute PE patients.

Ethics and dissemination:
As this is a protocol for a systematic review of previously published data, no ethical approval is required. Electronic dissemination of study results will be done through a peer-review publication or represented at a related conference.
Risk factors associated with the need for oxygen therapy in patients with COVID-19
Authors: Noh Chang Suk , Kim Won-Young , Baek Moon Seong 
Published: May 2021

Abstract
Respiratory failure is the major cause of death in patients with coronavirus disease (COVID-19). Data on factors affecting the need for oxygen therapy in early-stage COVID-19 are limited. This study aimed to evaluate the factors associated with the need for oxygen therapy in patients with COVID-19.
This is a retrospective study of consecutive COVID-19 patients who were hospitalized between February 27 and June 28, 2020, in South Korea. Logistic regression analyses were performed to identify the factors associated with the need for oxygen therapy.
Of the 265 patients included in the study, 26 (9.8%) received oxygen therapy, and 7 of these patients (29.2%) were transferred to a step-up facility, and 3 (11.5%) died. The median age of all patients was 46 years (IQR, 30–60 years), and the median modified early warning score at admission was 1 (IQR, 1–2). In a multivariate logistic regression analysis, being a current smoker (odds ratio [OR] 7.641, 95% confidence interval [CI] 1.686–34.630, P = .008), heart rate (OR 1.053, 95% CI 1.010–1.097, P = .014), aspartate aminotransferase values (OR 1.049, 95% CI 1.008–1.092, P = .020), blood urea nitrogen levels (OR 1.171, 95% CI 1.073–1.278, P < .001), and chest radiographic findings (OR 3.173, 95% CI 1.870–5.382, P < .001) were associated with oxygen therapy.
In patients with less severe COVID-19, the need for oxygen therapy is affected by smoking and elevated values of aspartate aminotransferase and blood urea nitrogen. Further research is warranted on the risk factors for deterioration in COVID-19 to efficiently allocate medical resources.
Dental caries and associated factors among Chinese children and adolescents
Authors: Huang Zhenxian , Su Meixuan , Wang Qiaojing , Li Wenjie , Jiang Haimin 
Published: May 2021

Abstract

Background:
Dental caries is a common disease under the action of many factors. Dental caries may occur in all age groups, among which children and adolescents are at high risk of dental caries. Early identification of the risk factors of dental caries is very important for clinical staff to prevent and intervene as soon as possible and reduce the incidence of dental caries. Although Chinese scholars have studied and summarized the risk factors of dental caries in children and adolescents, the conclusions are different. Therefore, in this study, meta-analysis was used to summarize the risk factors of dental caries in Chinese children and adolescents, and to explore the characteristics of high-risk groups of dental caries, so as to provide reference for early detection and prevention of dental caries.

Methods:
Medical specialty databases like PubMed, Embase, Cochrane Library, Web of Science, China Biology Medicine Database, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Database were consistently and exhaustively searched. According to the method of evidence-based medicine, the inclusion and exclusion criteria were established, and the meta-analysis of all eligible research results was carried out by using Review Manager 5.3 software.

Results:
We will disseminate the findings of this systematic review and meta-analysis via publications in peer-reviewed journals.

Conclusions:
Our study was carried out to estimate the pooled prevalence of dental caries and its associated factors among Chinese children and adolescents.

OSF Registration Number:
DOI 10.17605/OSF.IO/RA9D6.
Exploitation of sulfated glycosaminoglycan status for precision medicine of platinums in triple-negative breast cancer
Authors: Hampton James D. , Peterson Erica J. , Katner Samantha J. , H.Turner Tia , Alzubi Mohammad A. , Harrell J. Chuck , Dozmorov Mikhail G. , Gigliotti Pam J. , Kraskauskiene Vita , Shende Mayuri , Idowu Michael O. , Puchalapalli Madhavi , Hu Bin , Litovchick Larisa , Katsuta Eriko , Takabe Kazuaki , Farrell Nicholas P. , Koblinski Jennifer E. 
Published: May 2021

AbstractTriple negative breast cancer (TNBC) is a subtype of breast cancer lacking targetable biomarkers. TNBC is known to be most aggressive, and when metastatic is often drug resistant and uncurable. Biomarkers predicting response to therapy improve treatment decisions and allow personalized approaches for TNBC patients. This study explores sulfated glycosaminoglycan (sGAG) levels as a predictor of TNBC response to platinum therapy. sGAG levels were quantified in three distinct TNBC tumor models including cell line-derived, patient-derived xenograft (PDX) tumors, and isogenic models deficient in sGAG biosynthesis. Thein vivoantitumor efficacy of Triplatin, a sGAG-directed platinum agent, was compared in these models to the clinical platinum agent, carboplatin. We determined that >40% of TNBC PDX tissue microarray samples have high levels of sGAGs. Thein vivoaccumulation of Triplatin in tumors as well as antitumor efficacy of Triplatin positively correlated with sGAG levels on tumor cells, whereas carboplatin followed the opposite trend. In carboplatin-resistant tumor models expressing high levels of sGAGs, Triplatin decreased primary tumor growth, reduced lung metastases and inhibited metastatic growth in lungs, liver, and ovaries. sGAG levels served as a predictor of Triplatin sensitivity in TNBC. Triplatin may be particularly beneficial in treating patients with chemotherapy-resistant tumors who have evidence of residual disease after standard neoadjuvant chemotherapy. More effective neoadjuvant and adjuvant treatment will likely improve clinical outcome of TNBC.SignificanceTNBC is a heterogenous disease, often defined by the absence of a therapeutic target. Our recent results show sGAGs may provide a viable biomarker for Triplatin in patients with TNBC, producing a significant advantage over carboplatin in this setting. Selective precision medicine agents, such as Triplatin, that are active against chemotherapy-resistant disease and exploit molecular biomarkers like sGAGs may significantly benefit patients in this setting.
Designing Novel and Potent Inhibitors for Multi Drug-Resistant Tuberculosis: A Computational Approach
Authors: Idrees Muhammad , Ahmad Bashir , Israr Muhammad , Waqas Muhammad , Mukarram Shah Syed Muhammad , Khattak Aishma , Khan Saad Ahmad 
Published: May 2021

AbstractTuberculosis is a major global health problem and is still among the top 10 causes of death. The increasing rate of drug resistance to infectious agents has provoked an urgent need to discover novel anti-tuberculosis agents with novel modes of action. In this study, small molecule inhibitors of the proteins encoded by the drug resistant genes, i.e., katG, gyrA, pncA and rpoB of Mycobacterium tuberculosis (M. tuberculosis), were identified using computational methods. In the ligand base pharmacophore, an already reported four ligands for the four proteins encoded by the resistant genes of M. tuberculosis were selected for the generation of pharmacophores. The validated pharmacophores model of all the four proteins, generated on the basis of ligand base, were selected for further screening of ZINC drug like database. As screening results 486 structurally diverse hits for katG, 542 for PncA, 112 for rpoB and 365 for gyrA were mapped and filtered via Lipinski’s rule of five. Finally, on the basis of docking score and binding interactions, ten small molecules were selected for each protein as novel inhibitors. These selected novel inhibitors have significant interaction with the active site of the protein and a strong possibility to act as an additional starting opinion in the development of new and potential inhibitors. The result indicates that novel inhibitors could be a promising lead compound and be effective in treating sensitive as well as multi drug resistant tuberculosis.
Vascular tropism models of blood-borne microbial dissemination
Authors: Boczula Anna E. , Ly Amy , Ebady Rhodaba , Cho Janet , Anjum Zoha , Zlotnikov Nataliya , Persson Henrik , Odisho Tanya , Simmons Craig A. , Moriarty Tara J. 
Published: May 2021

SUMMARYSimilar to circulating tumour and immune cells, many blood-borne microbes preferentially “home” to specific vascular sites and tissues during hematogenous dissemination1–5. For many pathogens, the “postal codes” and mechanisms responsible for tissue-specific vascular tropism are unknown and have been challenging to unravel. Members of the Lyme diseaseBorreliella burgdorferispecies complex infect a broad range of mammalian tissues and exhibit complex strain-, species- and host-specific tissue tropism patterns. Intravenous perfusion experiments and intravital microscopy studies suggest that heterogeneous tissue tropism properties may depend on tissue-specific differences in host and microbial molecules supporting vascular interaction and extravasation. However, interpreting these studies can be complicated because of the immune-protective moonlighting (multitasking) properties of manyB. burgdorferiadhesins. Here, we investigated whetherB. burgdorferivascular interaction properties measured by live cell imaging and particle tracking in aorta, bladder, brain, joint and skin microvascular flow chamber models predict strain- and tissue-specific dissemination patternsin vivoThese studies identified strain- and endothelial cell type-specific interaction properties that accurately predictedin vivodissemination ofB. burgdorferito bladder, brain, joint and skin but not aorta, and indicated that dissemination mechanisms in all of these tissues are distinct. Thus, the ability to interact with vascular surfaces under physiological shear stress is a key determinant of tissue-specific tropism for Lyme disease bacteria. The methods and model systems reported here will be invaluable for identifying and characterizing the diverse, largely undefined molecules and mechanisms supporting dissemination of Lyme disease bacteria. These methods and models may be useful for studying tissue tropism and vascular dissemination mechanisms of other blood-borne microbes.
ProLung™-budesonideInhibits SARS-CoV-2 Replication and Reduces Lung Inflammation
Authors: Konduri Kameswari S. , Pattisapu Ram , Pattisapu Jogi , Konduri Girija G. , Zwetchkenbaum John , Roy Bidhan , Barman Monalisa , Frazier Adria , Hurst Brett L. , Düzgüneş Nejat 
Published: May 2021

ABSTRACTBackgroundInhaled budesonide benefits patients with COVID-19.ProLung™-budesonideenables the sustained, low dose administration of budesonide within a delivery vehicle similar to lung surfactant.ProLung™-budesonidemay offer anti-inflammatory and protective effects to the lung in COVID-19, yet it’s effect on SARS-CoV-2 replication is unknown.ObjectiveTo determine the efficacy ofProLung™-budesonideagainst SARS-CoV-2 infection in vitro, evaluate its ability to decrease inflammation, and airway hyperresponsiveness in an animal model of lung inflammation.MethodsSARS-CoV-2-infected Vero 76 cells were treated withProLung™-budesonide([0.03– 100 μg/ml]) for 3 days, and virus yield in the supernatant was measured. Ovalbumin-sensitized C57BL/6 mice received aerosolized (a)ProLung™-budesonideweekly, (b) only budesonide, either daily or weekly, or (c) weekly emptyProLung™-carrier(without budesonide). All treatment groups were compared to sensitized untreated, or normal mice using histopathologic examination, electron microscopy (EM), airway hyperresponsiveness (AHR) to Methacholine (Mch) challenge, and eosinophil peroxidase activity (EPO) measurements in bronchioalveolar lavage (BAL).ResultsProLung™-budesonideshowed significant inhibition on viral replication of SARS-CoV-2-infected cells with the selectivity index (SI) value > 24. WeeklyProLung™-budesonideand daily budesonide therapy significantly decreased lung inflammation and EPO in BAL.ProLung™-budesonidelocalized in type II pneumocytes, and was the only group to significantly decrease AHR, and EPO in BAL with Mch challengeConclusionsProLung™-budesonidesignificantly inhibited viral replication in SARS-CoV-2 infected cells. It localized into type II pneumocytes, decreased lung inflammation, AHR and EPO activity with Mch challenge. This novel drug formulation may offer a potential inhalational treatment for COVID-19.
SAMase of bacteriophage T3 inactivatesE. coli’smethionine S-adenosyltransferase by forming hetero-polymers
Authors: Simon-Baram Hadas , Kleiner Daniel , Shmulevich Fannia , Zarivach Raz , Zalk Ran , Tang Huayuan , Ding Feng , Bershtein Shimon 
Published: May 2021

ABSTRACTS-adenosylmethionine lyase (SAMase) of bacteriophage T3 degrades the intracellular SAM pools of the hostE. colicells, thus inactivating a crucial metabolite involved in plethora of cellular functions, including DNA methylation. SAMase is the first viral protein expressed upon infection and its activity prevents methylation of the T3 genome. Maintenance of the phage genome in a fully unmethylated state has a profound effect on the infection strategy — it allows T3 to shift from a lytic infection under normal growth conditions to a transient lysogenic infection under glucose starvation. Using single-particle Cryo-EM and biochemical assays, we demonstrate that SAMase performs its function by not only degrading SAM, but also by interacting with and efficiently inhibiting the host’s methionine S-adenosyltransferase (MAT) — the enzyme that produces SAM. Specifically, SAMase triggers open-ended head-to-tail assembly ofE. coliMAT into an unusual linear filamentous structure in which adjacent MAT tetramers are joined together by two SAMase dimers. Molecular dynamics simulations together with normal mode analyses suggest that the entrapment of MAT tetramers within filaments leads to an allosteric inhibition of MAT activity due to a shift to low-frequency high-amplitude active site-deforming modes. The amplification of uncorrelated motions between active site residues weakens MAT’s ability to withhold substrates, explaining the observed loss of function. We propose that the dual function of SAMase as an enzyme that degrades SAM and as an inhibitor of MAT activity has emerged to achieve an efficient depletion of the intracellular SAM pools.IMPORTANCESelf-assembly of enzymes into filamentous structures in response to specific metabolic cues has recently emerged as a widespread strategy of metabolic regulation. In many instances filamentation of metabolic enzymes occurs in response to starvation and leads to functional inactivation. Here, we report that bacteriophage T3 modulates the metabolism of the hostE. colicells by recruiting a similar strategy — silencing a central metabolic enzyme by subjecting it to phage-mediated polymerization. This observation points to an intriguing possibility that virus-induced polymerization of the host metabolic enzymes might be a common mechanism implemented by viruses to metabolically reprogram and subdue infected cells.
The ecological consequences and evolution of retron-mediated suicide as a way to protectEscherichia colifrom being killed by phage
Authors: Berryhill Brandon A. , Garcia Rodrigo , Manuel Joshua A. , Levin Bruce R. 
Published: May 2021

AbstractRetron were described in 1984 as DNA sequences that code for a reverse transcriptase and a unique single-stranded DNA/RNA hybrid called multicopy single-stranded DNA (msDNA). It would not be until 2020 that a function was shown for retrons, when compelling evidence was presented that retrons activate an abortive infection pathway in response to bacteriophage (phage) infection. When infected with the virulent mutant of the phage lambda, λVIR, and to a lesser extent, other phages, a retron designated Ec48 is activated, theEscherichia colibearing this element dies, and the infecting phage is lost. With the aid of a mathematical model, we explore thea prioriconditions under which retrons will protect bacterial populations from predation by phage and the conditions under which retron-bearing bacteria will evolve in populations without this element. UsingE. coliwith and without Ec48 and lVIR, we estimated the parameters of our model and tested the hypotheses generated from our analysis of its properties. Our models and experiments demonstrate that cells expressing a retron-mediated abortive infection system can protect bacterial populations. Our results demonstrate that retron bearing bacteria only have a competitive advantage under a limited set of conditions.
Proteomic traits vary across taxa in a coastal Antarctic phytoplankton bloom
Authors: McCain J. Scott P. , Allen Andrew E. , Bertrand Erin M. 
Published: May 2021

AbstractProduction and use of proteins is under strong selection in microbes, but it’s unclear how proteome-level traits relate to ecological strategies. We identified and quantified proteomic traits of eukaryotic and prokaryotic microbes through an Antarctic phytoplankton bloom using in situ metaproteomics. To do this, we first used simulations, cultures, and bioinformatic methods to rigorously assess our inferences about various proteomic traits and use these assessments to provide several practical recommendations for researchers using metaproteomics. Different taxa, rather than different environmental conditions, formed distinct clusters based on their ribosomal and photosynthetic proteomic proportions, and we propose that these characteristics relate to ecological differences. We defined and used a proteomic proxy for regulatory cost, which showed that SAR11 had the lowest regulatory cost of any taxa we observed at our summertime Southern Ocean study site. Haptophytes had lower regulatory cost than diatoms, which may underpin haptophyte-to-diatom bloom progression in the Ross Sea. Using metaproteomics, we have quantified several proteomic traits (ribosomal and photosynthetic proteomic proportions, regulatory cost) in eukaryotic and prokaryotic taxa, which can then be incorporated into trait-based models of microbial communities that reflect resource allocation strategies.