syedzayyan/paper_mill_benchmark huggingface dataset:
Methicillin-Resistant Staphylococcus aureus Meningitis from Transanal Migration of a Ventriculoperitoneal Shunt.

Bowel perforation is a rare complication of ventriculoperitoneal (vp) shunt placement that can result in anal protrusion of a vp shunt.Retrograde migration of bacteria through the shunt can lead to central nervous system (cns) infections, such as meningitis, most commonly caused by escherichia coli or other enteric pathogens.Here we present a case of methicillin-resistant staphylococcus aureus (mrsa) meningitis from transanal migration of a vp shunt.Case report a 2-month old female with a history of vp shunt placement presented to the emergency department (ed) after her mother noticed a tube in the patient's diaper.On examination, a white tube was noted to be protruding from the patient's anus.Plain radiographic shunt series showed an intact vp shunt terminating outside of the patient's body.Cerebrospinal fluid (csf) cultures grew mrsa.A diagnosis of mrsa meningitis secondary to spontaneous bowel perforation of a vp shunt was made.The patient went to the operating room for externalization of her shunt.Why should an emergency physician be aware of this?: to our knowledge, this is the first case of mrsa meningitis following transanal migration of a vp shunt to be reported in the literature.While anal protrusion of a vp shunt is rare, cns infection from this complication results in a high mortality rate.In addition, not all cases of bowel perforation from a vp shunt will present with the shunt exiting the body.Therefore, in a patient with a history of a vp shunt who presents with symptoms of meningitis, it is important for emergency physicians to heavily consider intestinal perforation by vp shunt as a possible etiology.

Journal: The Journal of emergency medicine (2019)
Publication types: Case Reports;Journal Article
Genomic landscape and immune-related gene expression profiling of epithelial ovarian cancer after neoadjuvant chemotherapy.

Platinum-based neoadjuvant chemotherapy followed by interval debulking surgery is an accepted treatment for patients with stage iii or iv epithelial ovarian cancer who are not suitable for primary debulking surgery.The identification of suitable adjuvant treatments in these patients is an unmet need.Here, we explore potential genomic characteristics (mutational and immune-associated expression profiles) in a series of patients undergoing neoadjuvant chemotherapy.Tumor samples from biopsy and interval debulking surgery were analyzed for mutational landscape and immune profiling, together with detailed immunohistochemistry using different immune cell markers, and correlated with clinicopathological characteristics and potential response to neoadjuvant chemotherapy.No major differences in the mutational landscape were observed in paired biopsy and surgery samples.Genomic loss of heterozygosity was found to be higher in patients with total/near-total tumor response.The immune gene expression profile after neoadjuvant chemotherapy revealed activation of several immune regulation-related pathways in patients with no/minimal or partial response.In parallel, neoadjuvant therapy caused a significant increase of tumor-infiltrating lymphocyte population abundance, primarily due to an augmentation of the cd8+ t cell population.Remarkably, these changes occurred irrespective of potential homologous recombination defects, such as those associated with brca1/2 mutations.Our study strengthens the use of loss of heterozygosity as a biomarker of homologous repair deficiency.The changes of immune states during neoadjuvant chemotherapy reveal the dynamic nature of tumor-host immune interactions and suggest the potential use of immune checkpoint inhibitors or their combination with poly-adp polymerase inhibitors in high stage and grade epithelial ovarian cancer patients undergoing neoadjuvant therapy.

Journal: NPJ precision oncology (2022)
Publication types: Journal Article
Perimortem Skeletal Sharp Force Trauma: Detection Reliability on CT Data, Demographics and Anatomical Patterns from a Forensic Dataset.

The increasing importance of trauma analysis by means of postmortem computed tomography (pmct) is insufficiently reflected in forensic curricula, nor are best practice manuals available.We attempt to detect sharp force bone lesions on pmct of closed forensic cases with the aims of assessing errors and pointing out patterns in anatomical location and manner of death (mod).We investigated 41 closed sharp force fatality cases, with available pmct and forensic reports.Two observers with different radiological training assessed the lesions on pmct scans (2d and 3d) for comparison with the reports.Between 3% (suicides) and 15.3% (homicides) of sharp force injuries caused visible bone lesions.While our observations were repeatable, each forensic investigation left a similar number of bone lesions undetected.Injury patterns differed between mod, with thoracic bone lesions being most frequent overall.Soft tissue injury location varied between the mod.Associations between mod and age as well as number of injuries were significant.The detection of bone lesions on pmct for untrained forensic specialists is challenging, curricula and pertinent manuals are desirable.With the low frequency of bone lesions compared to soft tissue injuries, we should be aware when analyzing decomposed bodies.

Journal: Biology (2022)
Publication types: Journal Article
The Effect of Carrier-Drug Ratios on Dissolution Performances of Poorly Soluble Drug in Crystalline Solid Dispersion System.

The choice of carrier and drug ratio are critical factors as far as the type of solid dispersion is concerned.Amorphous solid dispersion has been cited as the most desirable type among the different types of solid dispersion due to the benefit of amorphicity in increasing the drug solubility of a poorly soluble drug.Recent reports delineated that a partially crystalline solid dispersion system may perform better due to the inherent issue of solution mediated recrystallisation of a completely amorphous system.In oppose to the conventional choice of using amorphous polymer, this study aimed to investigate the use of a crystalline carrier, polyethylene glycol (peg) for dissolution enhancement of a model poorly soluble drug, flurbiprofen (fbp), a bcs class ii candidate.Solid dispersions of different fbp to peg 6000 molar ratios via solvent evaporation were prepared.Physical characterisation of preparations was performed using differential scanning calorimetry (dsc), attenuated total reflectance-fourier transform infrared spectroscopy (atr-ftir) and optical microscope.Dsc and atr-ftir analyses suggest the obtained solid dispersion exhibits crystalline fbp.This is then supported by the optical microscope analysis as the birefringence of crystals was noted.Further increasing the drug-carrier molar ratio to one-to-three and one-to-six showed that there was an amorphous fbp constituent in the system.Dsc analysis revealed the melting point depression of fbp by the carrier which signifies interaction between the drug and polymer.Dissolution study showed the solid dispersion of fbp improves the drug solubility and drug release compared to the pure drug.A higher carrier ratio in the formulation results in a higher drug release.

Journal: Journal of pharmaceutical sciences (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Clinical trial management: a profession in crisis?

Clinical trial managers play a vital role in the design and conduct of clinical trials in the uk.There is a current recruitment and retention crisis for this specialist role due to a complex set of factors, most likely to have come to a head due to the covid-19 pandemic.Academic clinical trial units and departments are struggling to recruit trial managers to vacant positions, and multiple influences are affecting the retention of this highly skilled workforce.Without tackling this issue, we face major challenges in the delivery on the department of health and social care's future of uk clinical research delivery implementation plan.This article, led by a leading network of and for uk trial managers, presents some of the issues and ways in which national stakeholders may be able to address this.

Journal: Trials (2022)
Publication types: Letter
Changes in the Quality Attributes of Selected Long-Life Food at Four Different Temperatures over Prolonged Storage.

This study reports the development of selected indicators affecting changes in food quality and safety of selected long-life canned (szeged goulash, canned chicken meat, pork pâté, canned tuna fish) and dehydrated (instant goulash soup) food during a two-year storage experiment at four different temperatures.The storage temperatures were selected to represent arctic (−18 °c), temperate (5 °c), subtropical (25 °c) and tropical (40 °c) climatic zones where such food is likely to be stored during, for example, humanitarian and military missions.Microorganism amounts below the detection limit (p < 0.05), regardless of the storage temperature (p ≥ 0.05), were monitored in canned samples.The contents of dry matter, fat and proteins did not change during storage, regardless of the storage temperature (p ≥ 0.05).During the 24-month storage, all food showed an increase in the level of ammonia (p < 0.05) and the tbars-value (p < 0.05), whereas the rate of increase in both parameters was significantly higher at higher storage temperatures (p < 0.05).The losses of individual amino acids during storage ranged from 5% rel.Calculated on the amino acid contents in month “0” up to 15% rel.(p < 0.05).With storage temperatures above the freezing point, the hardness values decreased with the increase in the storage temperature (p < 0.05) and prolongation of the storage period (p < 0.05).Moreover, with temperatures of −18 °c, the development of hardness, measured as the “decrease rate”, was significantly higher compared to the absolute values.

Journal: Foods (Basel, Switzerland) (2022)
Publication types: Journal Article
A static force model to analyze the nuclear deformation on cell adhesion to vertical nanostructures.

Vertical nanostructures have been found to induce the deformation of the nuclear envelope during cell adhesion.However, there has been a lack of quantitative analysis of the influence of nanostructures morphology on the degree of nuclear deformation.Here, a theoretical model was proposed to investigate the mechanism of nuclear deformation by analyzing the mechanical force balance.Based on the established model, we analyzed the effects of the morphology of the nanopillar array on nuclear deformation and gave the quantitative relationship of the deformation depth of the nucleus with the pitch and radius of nanopillars.Our theoretical results seem to show broad agreements with experimental observations, which implies that the work can provide useful guidance to the design of nanostructures for biomedical applications.

Journal: Soft matter (2022)
Publication types: Journal Article
Interacting Bioenergetic and Stoichiometric Controls on Microbial Growth.

Microorganisms function as open systems that exchange matter and energy with their surrounding environment.Even though mass (carbon and nutrients) and energy exchanges are tightly linked, there is a lack of integrated approaches that combine these fluxes and explore how they jointly impact microbial growth.Such links are essential to predicting how the growth rate of microorganisms varies, especially when the stoichiometry of carbon- (c) and nitrogen (n)-uptake is not balanced.Here, we present a theoretical framework to quantify the microbial growth rate for conditions of c-, n-, and energy-(co-) limitations.We use this framework to show how the c:n ratio and the degree of reduction of the organic matter (om), which is also the electron donor, availability of electron acceptors (eas), and the different sources of n together control the microbial growth rate under c, nutrient, and energy-limited conditions.We show that the growth rate peaks at intermediate values of the degree of reduction of om under oxic and c-limited conditions, but not under n-limited conditions.Under oxic conditions and with n-poor om, the growth rate is higher when the inorganic n (ninorg)-source is ammonium compared to nitrate due to the additional energetic cost involved in nitrate reduction.Under anoxic conditions, when nitrate is both ea and ninorg-source, the growth rates of denitrifiers and microbes performing the dissimilatory nitrate reduction to ammonia (dnra) are determined by both om degree of reduction and nitrate-availability.Consistent with the data, dnra is predicted to foster growth under extreme nitrate-limitation and with a reduced om, whereas denitrifiers are favored as nitrate becomes more available and in the presence of oxidized om.Furthermore, the growth rate is reduced when catabolism is coupled to low energy yielding eas (e.g., sulfate) because of the low carbon use efficiency (cue).However, the low cue also decreases the nutrient demand for growth, thereby reducing n-limitation.We conclude that bioenergetics provides a useful conceptual framework for explaining growth rates under different metabolisms and multiple resource-limitations.

Journal: Frontiers in microbiology (2022)
Publication types: Journal Article
Bioengineering of the digestive tract: approaching the clinic.

The field of regenerative medicine is developing technologies that, in the near future, will offer alternative approaches to either cure diseases affecting the gastrointestinal tract or slow their progression by leveraging the intrinsic ability of our tissues and organs to repair after damage.This article will succinctly illustrate the three technologies that are closer to clinical translation-namely, human intestinal organoids, sphincter bioengineering and decellularization, whereby the cellular compartment of a given segment of the digestive tract is removed to obtain a scaffold consisting of the extracellular matrix.The latter will be used as a template for the regeneration of a functional organ, whereby the newly generated cellular compartment will be obtained from the patient's own cells.Although clinical application of this technology is approaching, product development challenges are being tackled to warrant safety and efficacy.

Journal: Cytotherapy (2021)
Publication types: Journal Article
Novel XIAP mutation causing enhanced spontaneous apoptosis and disturbed NOD2 signalling in a patient with atypical adult-onset Crohn's disease.

X-linked inhibitor of apoptosis (xiap) is the most potent human inhibitor of apoptosis, and is also involved in nod2-dependent nfκb and mapk signalling cascade activation.The absence or defective function of xiap leads to the development of a rare and severe primary immunodeficiency known as x-linked lymphoproliferative syndrome type 2 (xlp-2), which is characterized by a triad of clinical manifestations, including a high incidence of haemophagocytic lymphohistiocytosis (hlh), lymphoproliferation and inflammatory bowel disease (ibd), usually with very early onset.Here, we present a novel xiap mutation identified in a patient with atypical adult-onset ibd complicated by relapsing hlh, splenomegaly and sarcoid-like disease.The c.266del a mutation in the xiap gene creates a premature stop codon, and causes a severe reduction in xiap protein expression.The mutation is also associated with impaired spontaneous and staurosporine- and pma-induced apoptosis accompanied by significantly increased expression of pro-apoptotic genes.We also confirmed the negative impact of this particular xiap mutation on nod2-dependent nfκb and mapk activation, while nod2-independent activation was found to be unaffected.Moreover, we assume that the mutation has an impact on the overproduction of il-12 and ifnγ, the shift towards the th1 immune response and increased numbers of central memory and effector memory cd4+ and cd8+ t cells.All these changes contribute to immune dysregulation and the clinical manifestation of xlp-2.

Journal: Cell death & disease (2020)
Publication types: Case Reports;Journal Article;Research Support, Non-U.S. Gov't
Single-cell mutation calling and phylogenetic tree reconstruction with loss and recurrence.

Motivation tumours evolve as heterogeneous populations of cells, which may be distinguished by different genomic aberrations.The resulting intra-tumour heterogeneity plays an important role in cancer patient relapse and treatment failure, so that obtaining a clear understanding of each patient's tumour composition and evolutionary history is key for personalized therapies.Single-cell sequencing (scs) now provides the possibility to resolve tumour heterogeneity at the highest resolution of individual tumour cells, but brings with it challenges related to the particular noise profiles of the sequencing protocols as well as the complexity of the underlying evolutionary process.Results by modelling the noise processes and allowing mutations to be lost or to reoccur during tumour evolution, we present a method to jointly call mutations in each cell, reconstruct the phylogenetic relationship between cells, and determine the locations of mutational losses and recurrences.Our bayesian approach allows us to accurately call mutations as well as to quantify our certainty in such predictions.We show the advantages of allowing mutational loss or recurrence with simulated data and present its application to tumour scs data.Availability and implementation sciφn is available at in.Supplementary information supplementary data are available at bioinformatics online.

Journal: Bioinformatics (Oxford, England) (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
The Role of Fast-Cycling Atypical RHO GTPases in Cancer.

The rho gtpases comprise a subfamily within the ras superfamily of small gtp-hydrolyzing enzymes and have primarily been ascribed roles in regulation of cytoskeletal dynamics in eukaryotic cells.An oncogenic role for the rho gtpases has been disregarded, as no activating point mutations were found for genes encoding rho gtpases.Instead, dysregulated expression of rho gtpases and their regulators have been identified in cancer, often in the context of increased tumor cell migration and invasion.In the new landscape of cancer genomics, activating point mutations in members of the rho gtpases have been identified, in particular in rac1, rhoa, and cdc42, which has suggested that rho gtpases can indeed serve as oncogenes in certain cancer types.This review describes the current knowledge of these cancer-associated mutant rho gtpases, with a focus on how their altered kinetics can contribute to cancer progression.

Journal: Cancers (2022)
Publication types: Journal Article;Review
Gross and Histopathological Findings in the First Reported Vaping-Induced Lung Injury Death in the United States.

The popularity of e-cigarettes (vaping) has been on the rise in recent years, but the adverse effects of vaping have been greatly unknown.In 2019, the use of vaping products has been linked to an outbreak of severe lung disease, some cases of which have progressed to death.One death attributed to vaping is presented with emphasis on the gross and histopathological findings from the autopsy.These findings were correlated with the patient's clinical course and medicolegal investigation to determine the cause of death.To our knowledge, this is the first confirmed death in the united states that was directly attributed to the use of vaping.

Journal: The American journal of forensic medicine and pathology (2020)
Publication types: Case Reports;Journal Article
An equation to estimate 24-hour total urine protein excretion rate in patients who underwent urine protein testing.

The urine protein-creatinine ratio (upcr) in a spot first-morning urine sample is used to estimate 24-h urine proteinuria (24h up) in patients who underwent urine protein testing.Upcr cannot be directly compared with 24-h proteinuria.Thus, an equation to estimate 24-h total protein excretion rate, using age, gender, and the upcr may improve its bias and accuracy in patients who underwent urine protein testing.Methods we simultaneously measured 24-h urine protein and the same day's first-morning spot urine from patients with kidney disease.Generalized linear and no-linear models, using age, gender, and upcr, were constructed to estimate for 24-h urine protein and the best model (nj equation) was selected to estimated 24 h up (e24h up).Results a total of 5435 paired samples (including a training cohort of 3803 patients and a validation cohort of 1632 patients) were simultaneously measured for upcr and 24-h urine protein.In the training cohort, the unadjusted upcr obviously underestimated 24-h urine protein when upcr ≤1.2 g/g (median bias - 0.17 g/24 h) and overestimated 24-h urine protein when upcr > 1.2 g/g (median bias 0.53 g/24 h).In the validation cohort, the nj equation performed better than the unadjusted upcr, with lower root mean square error (0.81 vs.1.02, p 2 g than lower values.Conclusions the nj e24h up equation is more accurate than unadjusted upcr to estimate 24 h up in patients with kidney disease and could be used for laboratory application.

Journal: BMC nephrology (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Mental health of nursing professionals during the COVID-19 pandemic: a cross-sectional study.

To identify the prevalence of and factors associated with: (1) major depressive episodes; (2) minor psychiatric disorders (mpds); and (3) suicidal ideation among nursing professionals from a municipality in southern brazil.Methods using a cross-sectional design, we recruited 890 nursing professionals linked to 50 primary care units, 2 walk-in clinics, 2 hospital services, 1 emergency room service, 1 mobile emergency care service, and 1 teleconsultation service, in addition to the municipal epidemiological surveillance service and the vacancy regulation center between june and july 2020.We used the patient health questionnaire-9 and the self-reporting questionnaire to evaluate the studied outcomes.Associations between the outcomes and variables related to sociodemographic profile, work, health conditions, and daily life were explored using poisson regression models with robust variance estimators.Results the observed prevalence of depression, mpds, and suicidal ideation were 36.6%, 44%, and 7.4%, respectively.Mpds were associated with the assessment of support received by the service as 'regular' (pr: 1.48; 95% ci: 1.19-1.85) or 'poor' (pr: 1.54; 95% ci: 1.23-1.94), with a reported moderate (pr: 1.63; 95% ci: 1.29-2.07), or heavy (pr: 2.54; 95% ci: 2.05-3.15) workload, and with suspected covid-19 infection (pr: 1.44; 95% ci: 1.25-1.66).Major depressive episodes were associated with a reported lack of personal protective equipment (pr: 1.20; 95% ci: 1.01-1.42), whereas suicidal ideation was inversely related to per capita income > 3 minimum monthly wages (pr: 0.28; 95% ci: 0.11-0.68), and positively related to the use of psychotropic drugs (pr: 3.14; 95% ci: 1.87-5.26).Conclusion our results suggest that nursing professionals' working conditions are associated with their mental health status.The need to improve working conditions through adequate dimensioning, support and proper biosafety measures is only heightened in the context of the covid-19 pandemic.

Journal: Revista de saude publica (2022)
Publication types: Journal Article