bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of differentiated dysplasia in the prediction of malignant transformation of oral leukoplakia
Authors: Wils Leon J. , Poell Jos B. , Peferoen Laura A. N. , Evren Ilkay , Brouns Elisabeth R. , de Visscher Jan G. A. M. , van der Meij Erik H. , Brakenhoff Ruud H. , Bloemena Elisabeth 
Published: September 2023

AbstractObjectiveOral leukoplakia is the most common oral potentially malignant disorder. Malignant transformation of oral leukoplakia occurs at an annual rate of 1%–7%. WHO‐defined classic epithelial dysplasia is an important predictor of malignant transformation of oral leukoplakia, but we have previously shown in a proof of concept study that prediction improves by incorporation of an architectural pattern of dysplasia, also coined as differentiated dysplasia. We aimed to analyze this finding in a larger cohort of patients.MethodFor this retrospective study 176 oral leukoplakia patients were included. Biopsies for all patients were assessed for the presence of dysplasia and analyzed for cytokeratin 13 and 17 expression. Moreover, the inter‐observer agreement for the diagnosis of differentiated dysplasia was determined.ResultsIn total, 33 of 176 patients developed oral squamous cell carcinoma during follow‐up. Presence of classic epithelial dysplasia increased cancer risk two‐fold (HR = 2.18, p = 0.026). Lesions without classic epithelial dysplasia could be further risk‐stratified by the presence of differentiated dysplasia (HR = 7.36, p < 0.001). Combined classic epithelial and differentiated dysplasia imparted a seven‐fold increased risk of malignant transformation (7.34, p = 0.001). Inter‐observer agreement for the diagnosis of dysplasia, including differentiated dysplasia, was moderate (κ = 0.56, p < 0.001).DiscussionThis study emphasizes the importance of the recognition of the architectural pattern of differentiated dysplasia as a separate entity for risk prediction of malignant transformation of oral leukoplakia. Presence of any pattern of dysplasia results in accurate prediction of malignant transformation risk of oral leukoplakia.
Arf6 is required for endocytosis and filamentous actin assembly during angiogenesis in vitro
Authors: Francis Caitlin R. , Bell Makenzie L. , Skripnichuk Marina M. , Kushner Erich J. 
Published: September 2023

AbstractObjectiveEndocytosis is a process vital to angiogenesis and vascular homeostasis. In pathologies where supraphysiological growth factor signaling underlies disease etiology, such as in diabetic retinopathy and solid tumors, strategies to limit chronic growth factor signaling by way of blunting endocytic processes have been shown to have tremendous clinical value. ADP ribosylation factor 6 (Arf6) is a small GTPase that promotes the assembly of actin necessary for clathrin‐mediated and clathrin‐independent endocytosis. In its absence, growth factor signaling is greatly diminished, which has been shown to ameliorate pathological signaling input in diseased vasculature. However, it is less clear if there are bystander effects related to loss of Arf6 on angiogenic behaviors. Our goal was to provide an analysis of Arf6's function in angiogenic endothelium, focusing on its role in actin and endocytosis as well as sprouting morphogenesis.MethodsPrimary endothelial cells were cultured in both 2D and 3D environments. Here, endothelial cells were fixed and stained for various proteins or transfected with fluorescently‐tagged constructs for live‐cell imaging.ResultsWe found that Arf6 localized to both filamentous actin and sites of endocytosis in two‐dimensional culture. Loss of Arf6 distorted both apicobasal polarity and reduced the total cellular filamentous actin content, which may be the primary driver underlying gross sprouting dysmorphogenesis in its absence.ConclusionsOur findings highlight that endothelial Arf6 is a potent mediator of both actin regulation and endocytosis and is required for proper sprout formation.
Tracing the Signature Dynamics of Language Teacher Immunity: A Retrodictive Qualitative Modeling Study
Authors: HIVER PHIL 
Published: September 2023

AbstractThis article describes a validation study using Retrodictive Qualitative Modeling, a framework for conducting research from a dynamic and situated perspective, to establish an empirical foundation for a new phenomenological construct—language teacher immunity. Focus groups (N = 44) conducted with second language (L2) practitioners and teacher educators and a cluster analysis of questionnaire data with a larger sample (N = 293) of K–12 language teachers were used to identify and corroborate typical archetypes across the spectrum of language teacher immunity outcomes. Serial in‐depth interviews were then conducted with representative respondents from each archetype (N = 18) to trace developmental trajectories and investigate how these profiles manifested phenomenologically in teachers’ motivated thought and instructional practices. Results indicate that teacher immunity is associated with practitioners’ psychological, emotional, and cognitive functioning in the social setting of the L2 classroom. These findings contribute to the field's understanding of how language teachers sustain their adaptivity, openness to change, psychological well‐being, and their sense of purpose and investment in students’ learning. Thus, teacher immunity has the potential to bridge individual and situative concerns in second language teacher education and the psychology of language teaching and learning.
Standing up for supervenience
Authors: Streumer Bart 
Published: September 2023

AbstractThere is a well‐known argument against irreducibly normative properties that appeals to the following claim about supervenience: for all possible worlds W and W*, if the instantiation of descriptive properties in W and W* is exactly the same, then the instantiation of normative properties in W and W* is also exactly the same. This claim used to be uncontroversial, but recently several philosophers have challenged it. Do these challenges undermine this argument? I argue that they do not, since the negation of this claim about supervenience has consequences that are much more implausible than the negations of key premises in these challenges.
Fair and efficient vaccine allocation: A generalized Gini index approach
Authors: Gutjahr Walter J. 
Published: September 2023

The paper proposes an optimization model for the allocation of vaccines to a heterogeneous population composed of several subpopulations with different sizes and epidemiological disease transmission parameters. As the objective, an aggregated function combining a standard utilitarian efficiency criterion with a Gini index–related penalty term is considered. Contrary to previous work, we adopt an outcome equity view: The inequity measure is not based on vaccination fractions or other input factors, but on the fractions of individuals escaping infection, as predicted by an susceptible‐infectious‐removed (SIR) model. An adjusted pro rata (APR) policy of vaccine allocation minimizing inequity in this outcome view is introduced, and a numerical procedure for its determination is presented. The concepts are developed both for the case of segregated subpopulations and for that of interactions between the subpopulations. Interestingly, in a large number of instances, the optimal solution under the aggregated objective function turns out to be identical to APR. Whether APR is locally or even globally optimal in a concrete case depends on the relation of an inequity aversion parameter to certain threshold values. While the local optimality threshold can be determined by linear programming, the determination of the global optimality threshold, as the vaccine allocation problem itself, is a problem of nonconvex optimization. We suggest an exact optimization approach for smaller instances, and propose algorithms building on particle swarm optimization for threshold determination and allocation optimization at larger instances. Extensions to alternative outcome measures such as the number of fatalities are presented as well. In addition to the investigation of randomly generated instances, two test cases from the literature are revisited in the context of the present work. Moreover, a new case study based on data from the COVID‐19 outbreak in Austria in 2020 is introduced and analyzed.
HLA‐haplotype redundancy and rareness in Canadian Blood Services' Stem Cell Registry and Cord Blood Bank: Novel metrics for optimizing utility
Authors: Bailey Adrian J. M. , Blake John , Ganz Kathy , Seftel Matthew D. , Allan David S. 
Published: September 2023

AbstractBackgroundThe utility of unrelated donor registries that support allogeneic hematopoietic cell transplantation could be optimized through greater understanding of redundancy and rareness of HLA phenotypes.MethodsHLA phenotype rareness was determined using known HLA haplotype frequencies. Donor redundancy was determined through pairwise comparison of donor HLA profiles within an inventory.ResultsAmong 61,730 registrants in the Canadian Blood Services (CBS) Stem Cell Registry (SCR) with high resolution HLA typing at 5 loci, 6.6% of HLA phenotypes were redundant with variation across ethnic groups (8.3% of Caucasian phenotypes; 8% of Native American/First Nations, 4.4% of Asia‐Pacific Islanders (API), 2.1% of Hispanic, 0.7% of African‐American (AFA), and 4.5% of other ethnicities). A total of 18.5% of registrants had redundant HLA phenotypes with variation across ethnic groups. All 3716 cord blood units in the CBS's cord blood bank (CBB) had high resolution HLA typing at 5 loci and 202 units were redundant (5.4%) comprising 78 HLA phenotypes, with varying rareness. Repeated HLA phenotypes were from Caucasian donors (77%), multiple ethnicity (13%), API (9%), and AFA (1%). Registrants and CBUs with AFA ethnicity had the rarest phenotypes while Caucasian ethnicity was associated with the most common HLA phenotypes.ConclusionsRedundancy was greater in the SCR compared to the CBB and was most common with CAU ethnicity. Recruiting non‐Caucasian registrants and continued cord blood banking should reduce redundancy. A sub‐inventory of redundant donors and cord blood units could support new uses for donor‐supported cellular therapies that do not require HLA matching.
Exploring avibactam and relebactam inhibition of
Klebsiella pneumoniae
carbapenemase D179N variant: role of the Ω loop-held deacylation water
Authors: Alsenani T. A. , Viviani S. L. , Papp-Wallace K. M. , Bonomo R. A. , van den Akker F. 
Published: September 2023

ABSTRACT

Klebsiella pneumoniae
carbapenemase-2 (KPC-2) presents a clinical threat as this β-lactamase confers resistance to carbapenems. Recent variants of KPC-2 in clinical isolates contribute to concerning resistance phenotypes.
Klebsiella pneumoniae
expressing KPC-2 D179Y acquired resistance to the ceftazidime/avibactam combination affecting both the β-lactam and the β-lactamase inhibitor yet has lowered minimum inhibitory concentrations for all other β-lactams tested. Furthermore,
Klebsiella pneumoniae
expressing the KPC-2 D179N variant also manifested resistance to ceftazidime/avibactam yet retained its ability to confer resistance to carbapenems although significantly reduced. This structural study focuses on the inhibition of KPC-2 D179N by avibactam and relebactam and expands our previous analysis that examined ceftazidime resistance conferred by D179N and D179Y variants. Crystal structures of KPC-2 D179N soaked with avibactam and co-crystallized with relebactam were determined. The complex with avibactam reveals avibactam making several hydrogen bonds, including with the deacylation water held in place by Ω loop. These results could explain why the KPC-2 D179Y variant, which has a disordered Ω loop, has a decreased affinity for avibactam. The relebactam KPC-2 D179N complex revealed a new orientation of the diazabicyclooctane (DBO) intermediate with the scaffold piperidine ring rotated ~150° from the standard DBO orientation. The density shows relebactam to be desulfated and present as an imine-hydrolysis intermediate not previously observed. The tetrahedral imine moiety of relebactam interacts with the deacylation water. The rotated relebactam orientation and deacylation water interaction could potentially contribute to KPC-mediated DBO fragmentation. These results elucidate important differences that could aid in the design of novel β-lactamase inhibitors.
Oh my gut! Is the microbial origin of neurodegenerative diseases real?
Authors: Walker Alyssa , Czyz Daniel M. 
Published: September 2023

ABSTRACT
There is no cure or effective treatment for neurodegenerative protein conformational diseases (PCDs), such as Alzheimer’s or Parkinson’s diseases, mainly because the etiology of these diseases remains elusive. Recent data suggest that unique changes in the gut microbial composition are associated with these ailments; however, our current understanding of the bacterial role in the pathogenesis of PCDs is hindered by the complexity of the microbial communities associated with specific microbiomes, such as the gut, oral, or vaginal microbiota. The composition of these specific microbiomes is regarded as a unique fingerprint affected by factors such as infections, diet, lifestyle, and antibiotics. All of these factors also affect the severity of neurodegenerative diseases. The majority of studies that reveal microbial contribution are correlational, and various models, including worm, fly, and mouse, are being utilized to decipher the role of individual microbes that may affect disease onset and progression. Recent evidence from across model organisms and humans shows a positive correlation between the presence of gram-negative enteropathogenic bacteria and the pathogenesis of PCDs. While these correlational studies do not provide a mechanistic explanation, they do reveal contributing bacterial species and provide an important basis for further investigation. One of the lurking concerns related to the microbial contribution to PCDs is the increasing prevalence of antibiotic resistance and poor antibiotic stewardship, which ultimately select for proteotoxic bacteria, especially the gram-negative species that are known for intrinsic resistance. In this review, we summarize what is known about individual microbial contribution to PCDs and the potential impact of increasing antimicrobial resistance.
Transfusion-transmitted
Babesia
spp.: a changing landscape of epidemiology, regulation, and risk mitigation
Authors: Drews Steven J. , Kjemtrup Anne M. , Krause Peter J. , Lambert Grayson , Leiby David A. , Lewin Antoine , O'Brien Sheila F. , Renaud Christian , Tonnetti Laura , Bloch Evan M. 
Published: September 2023

ABSTRACT

Babesia
spp. are tick-borne parasites with a global distribution and diversity of vertebrate hosts. Over the next several decades, climate change is expected to impact humans, vectors, and vertebrate hosts and change the epidemiology of
Babesia
. Although humans are dead-end hosts for tick-transmitted
Babesia
, human-to-human transmission of
Babesia
spp. from transfusion of red blood cells and whole blood-derived platelet concentrates has been reported. In most patients, transfusion-transmitted
Babesia
(TTB) results in a moderate-to-severe illness. Currently, in North America, most cases of TTB have been described in the United States. TTB cases outside North America are rare, but case numbers may change over time with increased recognition of babesiosis and as the epidemiology of
Babesia
is impacted by climate change. Therefore, TTB is a concern of microbiologists working in blood operator settings, as well as in clinical settings where transfusion occurs. Microbiologists play an important role in deploying blood donor screening assays in
Babesia
endemic regions, identifying changing risks for
Babesia
in non-endemic areas, investigating recipients of blood products for TTB, and drafting TTB policies and guidelines. In this review, we provide an overview of the clinical presentation and epidemiology of TTB. We identify approaches and technologies to reduce the risk of collecting blood products from
Babesia
-infected donors and describe how investigations of TTB are undertaken. We also describe how microbiologists in
Babesia
non-endemic regions can assess for changing risks of TTB and decide when to focus on laboratory-test-based approaches or pathogen reduction to reduce TTB risk.
Safety and tolerability of tedizolid as oral treatment for bone and joint infections
Authors: Miller Loren G. , Flores Evelyn A. , Launer Bryn , Lee Pamela , Kalkat Praneet , Derrah Kelli , Agrawal Shalini , Schwartz Matthew , Steele Grant , Kim Tae , Kuvhenguhwa Maita S. 
Published: September 2023

ABSTRACT

Bone and joint infections (BJIs) are common infections increasingly managed with oral therapy. However, there are limited safe oral options for many Gram-positive pathogens. In animal studies and short-term human use, tedizolid lacks the hematologic and neurologic toxicity of the other available oxazolidinone, linezolid. However, there are limited prospective safety data. We conducted an open-label, non-comparative trial of oral tedizolid for BJI treatment. Primary outcomes were safety and cure rate. Eligible patients had a BJI caused by documented or suspected Gram-positive pathogen, required 4–12 weeks of therapy, and did not have myelosuppression or peripheral/optic neuropathy. Subjects underwent weekly evaluation for cytopenias and neuropathy. We enrolled 44 subjects; five were lost to follow-up. Two subjects did not complete planned treatment because of rash (
n
= 1) and urgent surgery (
n
= 1). Of 37 patients with evaluable outcomes, 17 (46%) had hardware-associated infection, 13 (35%) had osteomyelitis, 5 (14%) had prosthetic joint infection, and 2 (5%) had other BJIs. Median (mean, range) treatment duration was 12 (10.1, 4–12) weeks. There were no cases of cytopenias or peripheral or optic neuropathy. Treatment cure occurred in 13 (35%); 19 (51%) required antibiotic continuation after 12 weeks of tedizolid related to retained hardware at the BJI site, and failure occurred in four (11%), two unlikely, one possibly, and one probably due to tedizolid. We found that oral tedizolid was well tolerated for prolonged BJI treatment without significant toxicity. Clinical failure rate was similar to that of other published BJI investigations. (This study has been registered at Clinicaltrials.gov under identifier NCT03009045.)

IMPORTANCE
Bone and joint infections are common infections with limited effective and safe oral options for Gram-positive infections. The largest prospective clinical trial of tedizolid therapy for bone and joint infections enrolled 44 patients and tested each in person weekly with detailed safety monitoring including tests for leukopenia, anemia, thrombocytopenia, peripheral neuropathy, and optic neuropathy for up to 12 weeks. Findings demonstrated tedizolid was generally well tolerated and there were no incident cases of cytopenias or neuropathy. Cure rates were similar to that in other bone and joint infection studies. In summary, oral tedizolid appears to be a well-tolerated oral option for Gram-positive bone and joint infections.
Supplemental Material: Ice-rafted dropstones at midlatitudes in the Cretaceous of continental Iberia
Authors: Rodríguez-López Juan Pedro , Liesa Carlos L. , al. et 
Published: September 2023

<p>(I) Supplementary text (geological setting, sedimentology and morphometric analysis of dropstones, FESEM analysis of quartz grains, and methods); (II) supplementary Figures. S1–S7; and (III) supplementary Table S1. </p>
Clinical outcomes ofStaphylococcus capitisisolation from neonates, England, 2015–2021: a retrospective case–control study
Authors: Yuan Jin-Min , Nugent Christopher , Wilson Allegra , Verlander Neville Q , Alexander Eliza , Fleming Paul , Modi Neena , Oughham Kayleigh , Ratnaraja Natasha , Wan Yu , Thorn Louise , Felgate Heather , Webber Mark A , Ogundipe Enitan , Brown Colin S , Paranthaman Karthik , Demirjian Alicia 
Published: September 2023

ObjectiveStaphylococcus capitis, a coagulase-negative staphylococci (CoNS) species, has been increasingly detected from UK sterile site samples and has caused neonatal unit outbreaks worldwide. We compared survival to discharge and 30-day mortality for the detection ofS. capitisversus other CoNS species.MethodsIn this retrospective case–control study, we included hospitalised infants with any CoNS species detected from a normally sterile body site up to 90 days of age. We linked English laboratory reports from the Second Generation Surveillance System database, mortality data from the Personal Demographics Service, and neonatal unit admissions from the National Neonatal Research Database. In primary analysis, multivariable logistic regression was used, with two co-primary outcomes: survival to discharge and death within 30 days of positive specimen date. Sensitivity analyses using multiply imputed datasets followed.ResultsWe identified 16 636 CoNS episodes relating to 13 745 infants. CoNS episodes were highest among infants born extremely preterm (22–27 weeks) and with extremely low birth weight (400–999 g). In primary analysis, there were no differences in survival to discharge (p=0.71) or 30-day mortality (p=0.77) between CoNS species. In sensitivity analyses, there were no differences in outcomes between infection with four of the most common CoNS species (Staphylococcus epidermidis, S. capitis,Staphylococcus haemolyticusandStaphylococcus warneri) but the remaining CoNS species were at higher risk of adverse outcomes when treated in aggregate.ConclusionInfants withS. capitisdetected from sterile site samples did not experience significant differences in either survival to discharge or 30-day mortality compared with infants with detection of other common CoNS species.
Systematic comparison of Mendelian randomisation studies and randomised controlled trials using electronic databases
Authors: Sobczyk Maria K , Zheng Jie , Davey Smith George , Gaunt Tom R 
Published: September 2023

ObjectiveTo scope the potential for (semi)-automated triangulation of Mendelian randomisation (MR) and randomised controlled trials (RCTs) evidence since the two methods have distinct assumptions that make comparisons between their results invaluable.MethodsWe mined ClinicalTrials.Gov, PubMed and EpigraphDB databases and carried out a series of 26 manual literature comparisons among 54 MR and 77 RCT publications.ResultsWe found that only 13% of completed RCTs identified in ClinicalTrials.Gov submitted their results to the database. Similarly low coverage was revealed for Semantic Medline (SemMedDB) semantic triples derived from MR and RCT publications –36% and 12%, respectively. Among intervention types that can be mimicked by MR, only trials of pharmaceutical interventions could be automatically matched to MR results due to insufficient annotation with Medical Subject Headings ontology. A manual survey of the literature highlighted the potential for triangulation across a number of exposure/outcome pairs if these challenges can be addressed.ConclusionsWe conclude that careful triangulation of MR with RCT evidence should involve consideration of similarity of phenotypes across study designs, intervention intensity and duration, study population demography and health status, comparator group, intervention goal and quality of evidence.