bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating Reception Center Models for Radiation Response Screening Capacity and Throughput Predictions
Authors: Finklea Lauren , Goff Robert , Houghton Erica 
Published: March 2024

Abstract

Introduction: The current fleet of nuclear reactors in the United States is mandated to provide evidence that surrounding jurisdictions can screen their populations should an incident occur. Capacity can be measured as throughput in reception centers used for screening. Due to the significant staffing and resources required to exercise screening capacity, most jurisdictions typically perform smaller exercises and use models to estimate their overall throughput. Objective: To evaluate the applicability and realism of current throughput models and practices. Methods: Throughput capacity for radiation screening is estimated with a mathematical model derived by the Federal Emergency Management Agency (FEMA). The Centers for Disease Control and Prevention developed a discrete event simulation model as a tool, SimPLER, to evaluate capacity and make throughput predictions. Model estimates will be compared and evaluated using timing data collected at a large-scale exercise. Results: The FEMA model estimated a throughput 41.2% higher than the actual radiation screening throughput, while the SimPLER model provided identical values. The FEMA and SimPLER models’ predicted throughputs were 50% and 3.8%, respectively, higher than total exercise throughput. Applying each model to the throughput projections for a 12-hour shift, the FEMA model estimates ranged from 665 to 6,646 people and the SimPLER model yielded an estimated throughput of 1,809 people with a standard deviation of 74.6. Conclusion: Discrete event simulation models, such as SimPLER, may provide more realistic and accurate predictions of radiation screening and throughput capacity of reception centers than mathematical models such as the FEMA model.
Clinicopathologic Overlap of Vulvar Psoriasis and Candidiasis
Authors: Day Tania , Chapman-Burgess Erika , Scurry James 
Published: March 2024

Objectives
The study’s aim is to assess if vulvar psoriasis and candidiasis may be distinguished by clinical presentation and histopathologic appearance.

Methods
The pathology database identified biopsies with corneal or subcorneal neutrophils, acanthosis, and dermal lymphocytic infiltrate. Exclusions were age younger than 18 years and unavailable or uninterpretable slides. Clinical data included demographics, comorbid conditions, symptoms, examination, microbiology, treatment, and response. Histopathologic review documented site, thickness, and characteristics of stratum corneum and epidermis, distribution of neutrophils, and infiltrate. Cases were stratified by microbiologic presence or absence of Candida albicans.

Results
Biopsies from 62 women with median age of 60 years were associated with C. albicans on vulvovaginal culture in 28 (45%), whereas 26 (42%) were negative, and 8 (13%) lacked microbiologic assessment. Swab-positive women were more likely to have diabetes, receive prereferral estrogen, and report vulvar pain. Specialist clinical impression was candidiasis in 33 (53%), psoriasis in 11 (18%), comorbid candidiasis and psoriasis in 7 (11%), dermatitis in 10 (16%), and unknown in 2 (3%). Visible fungal organisms occurred in 16 (26%) cases and were associated with diabetes and satellite lesions. Other than presence of organisms, there were no histopathologic differences stratified by microbiologic result.

Conclusions
The histopathologic triad of corneal/subcorneal neutrophils, acanthosis, and dermal lymphocytic infiltrate is common to vulvar psoriasis and candidiasis, and clinical features do not reliably distinguish between them. Microbiologic assessment and single-agent treatment are useful strategies to clarify the diagnosis.
Psychedelic Therapy: A Primer for Primary Care Clinicians—Historical Perspective and Overview
Authors: Tabaac Burton J. , Shinozuka Kenneth , Arenas Alejandro , Beutler Bryce D. , Cherian Kirsten , Evans Viviana D. , Fasano Chelsey , Muir Owen S. 
Published: March 2024

Background:
Psychedelic drugs have recently emerged as plausibly effective pharmacological agents for the management of depression, anxiety, and other neuropsychiatric conditions, including those that are treatment-resistent. The latter half of the 20th century marked a revolution in the treatment of mental illnesses, exemplified by the introduction of selective serotonin reuptake inhibitors and other pharmacological agents. Nevertheless, mental illness remains a major public health crisis, affecting nearly one billion individuals worldwide.

Areas of Uncertainty:
Because of the decades-long status of several psychedelics as Schedule I drugs, there have not been very many large, double-blind, randomized controlled trials of psychedelics. Owing to small sample sizes, there may be rare yet serious adverse events that have not been reported in the clinical trials thus far.

Therapeutic Advances:
Esketamine, a dissociative hallucinogen drug, was approved for the management of major depressive disorder by the Food and Drug Administration in 2019. As of January 2024, two Phase III trials of 3,4-methylenedioxymethamphetamine (MDMA), a synthetic drug that inhibits the serotonin transporter, have been completed; the results indicate that MDMA is superior to existing pharmacological treatments for post-traumatic stress disorder. A phase III trial of psilocybin, a naturally occurring serotonin receptor partial agonist, is currently underway. The following series details the current state of research in psychedelic therapeutics, including lysergic acid diethylamide (LSD), N-N-dimethyltryptamine (DMT) and ayahuasca, psilocybin, ibogaine, MDMA, and ketamine.

Limitations:
While initial clinical trials of psychedelics for depression were very promising, trials of psilocybin with larger sample sizes (100+ participants) suggest that its remission rate is 25%–29%. This is about the same as the remission rate of antidepressants, which is roughly 30% according to the landmark STAR*D trial.

Conclusions:
Psychedelic drugs and structural derivatives offer a great deal of promise for the management of a wide range of psychiatric morbidities. It is imperative that clinicians become familiar with these novel agents and learn how to integrate psychedelic therapy with the rest of their care through open communication and referral.
Cost-effectiveness Analysis of Single-Use Duodenoscope Applied to Endoscopic Retrograde Cholangiopancreatography
Authors: Nicolás-Pérez David , Gimeno-García Antonio Zebenzuy , Romero-García Rafael Joaquín , Castilla-Rodríguez Iván , Hernandez-Guerra Manuel 
Published: March 2024

Objectives
Secondary infections due to transmission via the duodenoscope have been reported in up to 3% of endoscopic retrograde cholangiopancreatographies. The use of single-use duodenoscopes has been suggested. We investigate the cost-effectiveness of these duodenoscopes use in cholangiopancreatography.

Materials and Methods
A cost-effectiveness analysis was implemented to compare the performance of cholangiopancreatographies with reusable duodenoscopes versus single-use duodenoscopes. Effectiveness was analyzed by calculating quality-adjusted life years (QALY) from the perspective of the National Health System. Possibility of crossover from single-use to reusable duodenoscopes was considered. A willingness-to-pay of €25,000/QALY was set, the incremental cost-effectiveness ratio (ICER) was calculated, and deterministic and probabilistic sensitivity analyses were performed.

Results
Considering cholangiopancreatographies with single-use and reusable duodenoscopes at a cost of €2900 and €1333, respectively, and a 10% rate of single-use duodenoscopes, ICER was greater than €3,000,000/QALY. A lower single-use duodenoscope cost of €1211 resulted in an ICER of €23,583/QALY. When the unit cost of the single-use duodenoscope was €1211, a crossover rate of more than 9.5% made the use of the single-use duodenoscope inefficient.

Conclusions
Single-use duodenoscopes are cost-effective in a proportion of cholangiopancreatographies if its cost is reduced. Increased crossover rate makes single-use duodenoscope use not cost-effective.
Pancreatic Cysts Greater Than 1 cm Are Associated With an Increased Risk for Developing Pancreatic Cancer in Individuals From Pancreatic-Cancer Prone Kindreds Undergoing Surveillance
Authors: Aijazi Muaz , Fasanella Kenneth E. , McGrath Kevin , Smith Lynette M. , Singhi Aatur D. , Brand Randall E. 
Published: March 2024

Background
The International Cancer of the Pancreas Screening Consortium recommended annual imaging for individuals at increased risk for developing a pancreatic ductal adenocarcinoma (PDAC) who did not have concerning pancreatic findings or a cyst <3 cm without worrisome features. We aimed to determine if 3-cm cyst size accurately predicted advanced precursor lesions in high-risk individuals undergoing surveillance.

Methods
Imaging for high-risk individuals (HRIs) undergoing PDAC surveillance from 2007 to 2021 was reviewed and pancreatic abnormalities were recorded including dominant cyst size and number of cysts. Subjects were excluded if they had the following: (1) no follow-up imaging after baseline, (2) solid lesion at baseline, or (3) development of solid lesion without having cyst on prior imaging.

Results
Five of the 77 HRIs found to have a cystic lesion on surveillance developed a PDAC: 3 with cystic lesion >1 cm as compared with only 2 of 67 HRIs with cystic lesions <1 cm (P < 0.05). None of these cysts developed worrisome findings and 4/5 PDACs did not arise from visualized cystic precursor lesion.

Conclusions
Patients with a cyst ≥1 cm were at increased risk for developing PDAC compared with patients with cyst <1 cm. Pancreatic ductal adenocarcinoma usually did not arise from a recognized cystic lesion.
Effect of pain on activity and participation in individuals with unilateral lower-extremity amputation based on the International Classification of Functioning, Disability, and Health
Authors: Yerli Sibel , Erbahçeci Fatih , Kerem Günel Mintaze 
Published: March 2024

Background:
Amputation is a major life-changing event and is regarded as one of the loading causes of permanent disability. However, amputation often causes changes in painful and nonpainful sensory experiences. Pain after amputation has been shown to increase functional limitations caused by limb loss and lower quality of life.

Objective:
This study aimed to examine the effect of pain on activity and participation in individuals with unilateral below-knee amputations according to the International Classification of Functioning, Disability, and Health.

Study Design:
Cross-sectional study.

Methods:
In the study, 64 individuals were divided into 2 groups: those who experienced pain and those who did not. Group 1 included 33 below-knee amputees who experienced pain (27 males, mean age 43.9 ± 12.6 years) and Group 2 included 31 below-knee amputees who did not experience pain (25 males, mean age 47.4 ± 12.1 years). The McGill Pain Questionnaire and visual analog scale were used to assess pain, the Prosthetic Limb Users Survey of Mobility was used to assess activity, and the Reintegration to Normal Living Index was used to assess participation.

Results:
Demographic characteristics of the 2 groups were statistically insignificant (P > 0.05). The nonpainful group had significantly higher activity and participation scores than the painful group (P < 0.001).

Conclusions:
It was found that phantom pain and stump pain in below-knee amputees limited activity and participation. It was also shown that phantom pain has a more negative effect on the activity level of individuals than stump pain.
Derivation of a Mortality Prediction Model in Critical Care Patients with Cirrhosis and Sepsis
Authors: Piccolo Serafim Laura , Simonetto Douglas A. , Choi Dae Hee , Weister Timothy J. , Hanson Andrew C. , Kamath Patrick S. , Gajic Ognjen , Gallo de Moraes Alice 
Published: March 2024

Abstract

Objective
To develop a predictive model for in-hospital mortality in critically ill patients with cirrhosis and sepsis, using clinical and laboratory data.

Design
Retrospective cohort study.

Setting
Medical and mixed ICUs of a tertiary medical center.

Patients
Cirrhotic adults admitted with sepsis to the ICUs from January of 2007 to May of 2017.

Interventions
None.

Measurements and Main Results
Out of 2595 ICU admissions of patients with cirrhosis, 277 with first ICU admission for sepsis were included in the analysis, and 37% died in the hospital. Patients who stayed in the ICU for at least 6 hours (n = 275) were considered for the multivariate model. Ten-fold cross-validation was used to estimate best parameter values and model performance, and the final model was chosen as the model maximizing area under the receiver-operating characteristic curve. Variables in order of impact were APACHE III score, initial serum lactate, conjugated bilirubin, serum creatinine, MELD score, age, BMI, and serum hemoglobin. The final best model from cross-validation presented an AUC of 0.75, using a cut-point of 50% estimated probability, sensitivity and specificity were 0.46 and 0.90, respectively, with PPV of 0.72 and NPV of 0.74. These results were similar to the APACHE III only model (AUC = 0.74, Sensitivity = 0.43, Specificity = 0.89, PPV = 0.69, NPV = 0.73).

Conclusions
The combination of initial serum lactate level, conjugated bilirubin, initial serum creatinine, MELD score, age, BMI, and serum hemoglobin did not yield meaningful improvement in the AUC and did not provide advantage over the APACHE III score for the prediction of in-hospital mortality in critically ill patients with cirrhosis and sepsis.
Assessing the Performance of Zero-Shot Visual Question Answering in Multimodal Large Language Models for 12-Lead ECG Image Interpretation
Authors: Seki Tomohisa , Kawazoe Yoshimasa , Akagi Yu , Takiguchi Toru , Ohe Kazuhiko 
Published: March 2024

AbstractLarge Language Models (LLM) are increasingly multimodal, and Zero-Shot Visual Question Answering (VQA) shows promise for image interpretation. If zero-shot VQA can be applied to a 12-lead electrocardiogram (ECG), a prevalent diagnostic tool in the medical field, the potential benefits to the field would be substantial. This study evaluated the diagnostic performance of zero-shot VQA with multimodal LLMs on 12-lead ECG images. The results revealed that multimodal LLM tended to make more errors in extracting and verbalizing image features than in describing preconditions and making logical inferences. Even when the answers were correct, erroneous descriptions of image features were common. These findings suggest a need for improved control over image hallucination and indicate that performance evaluation using the percentage of correct answers to multiple-choice questions may not be sufficient for performance assessment in VQA tasks.
CHAI: Consensus Clustering Through Similarity Matrix Integration for Cell-Type Identification
Authors: Lodi Musaddiq K , Lodi Muzammil , Osei Kezie , Ranganathan Vaishnavi , Hwang Priscilla , Ghosh Preetam 
Published: March 2024

ABSTRACTSeveral methods have been developed to computationally predict cell-types for single cell RNA sequencing (scRNAseq) data. As methods are developed, a common problem for investigators has been identifying the best method they should apply to their specific use-case. To address this challenge, we present CHAI (consensus Clustering tHrough similArIty matrix integratIon for single cell type identification), a wisdom of crowds approach for scRNAseq clustering. CHAI presents two competing methods which aggregate the clustering results from seven state of the art clustering methods: CHAI-AvgSim and CHAI-SNF. Both methods demonstrate improved performance on a diverse selection of benchmarking datasets, besides also outperforming a previous consensus clustering method. We demonstrate CHAI’s practical use case by identifying a leader tumor cell cluster enriched with CDH3. CHAI provides a platform for multiomic integration, and we demonstrate CHAI-SNF to have improved performance when including spatial transcriptomics data. CHAI is intuitive and easily customizable; it provides a way for users to add their own clustering methods to the pipeline, or down-select just the ones they want to use for the clustering aggregation. CHAI is available as an open source R package on GitHub:https://github.com/lodimk2/chai
Heterochromatin dynamics during the initial stages of sexual development inPlasmodium falciparum
Authors: Nhim Sandra , Tintó-Font Elisabet , Casas-Vila Núria , Michel-Todó Lucas , Cortés Alfred 
Published: March 2024

ABSTRACTAsexual replication ofPlasmodium falciparumin the human blood results in exponential parasite growth and causes all clinical symptoms of malaria. However, at each round of the replicative cycle, some parasites convert into sexual precursors called gametocytes, which are essential for transmission to mosquito vectors. After sexual conversion, parasites develop through the sexual ring stage and then gametocyte stages I to V before they are infective to mosquitoes. Heterochromatin, a type of chromatin generally refractory to gene expression, plays an important role in the regulation of sexual conversion by silencing the master regulator of the process, PfAP2-G, in asexual parasites. Additionally, previous reports have described changes in the genome-wide distribution of heterochromatin in stage II/III or older gametocytes, including expansion of heterochromatin at several subtelomeric regions and reduced occupancy at a few specific loci. However, it is not known if these changes occur concomitantly with sexual conversion or at a later time during gametocyte development. Using a transgenic line in which sexual conversion can be conditionally induced, here we show that the genome-wide distribution of heterochromatin at the initial stages of sexual development (i.e., sexual rings and stage I gametocytes) is almost identical to parasites at asexual blood stages, and major changes do not occur until stage II/III. We also show that transcriptional changes associated with sexual development typically precede, rather than follow, changes in heterochromatin occupancy at their loci, which raises the possibility that PfAP2-G operates as a pioneer factor.IMPORTANCEEpigenetic processes and chromatin structure play an important role in the regulation of gene expression in malaria parasites. In particular, a type of chromatin called heterochromatin is involved in the regulation (silencing) of many genes. Parasite sexual development is essential for transmission to mosquito vectors. Here we characterised the global distribution of heterochromatin at different stages of sexual development, and found that initially it is identical to asexual blood stages, but at later transmission stages it is altered. This informs about the putative roles of general heterochromatin redistribution in parasite life cycle progression. By integrating multi-omic datasets, we also found that changes in the expression of several genes precede changes in their heterochromatin occupancy. This indicates that during sexual development some genes can be activated in spite of having heterochromatin.
Septin filament assembly assist the lateral organization of membranes
Authors: El Alaoui Fatima , Al-Akiki Isabelle , Ibanes Sandy , Lyonnais Sébastien , Sanchez-Fuentes David , Desgarceaux Rudy , Cazevieille Chantal , Blanchard Marie-Pierre , Parmeggiani Andrea , Carretero-Genevrier Adrian , Piatti Simonetta , Picas Laura 
Published: March 2024

ABSTRACTCompartmentalized interactions of plasma membrane components are essential to support many cell functions, from signaling to cell division, adhesion, migration, or phagocytosis. Cytoskeletal-membrane interactions play an important role in forming membrane compartments, and this feature has been primarily studied through the actin cytoskeleton. Unlike actin, septins directly interact with membranes, acting as scaffolds to recruit proteins to specific cellular locations and as structural diffusion barriers for membrane components. However, how septins interact with and remodel the local membrane environment is unclear. Here we combined minimal reconstituted systems based on fluorescence microscopy and quantitative atomic force microscopy together with live yeast cell imaging and STED microscopy to study septin-mediated membrane organization. Our results show that septins self-assembly into filament-based sub-micrometric patches and high-order structures prompt their membrane-organizing rolein vitroand in yeast cells, respectively. Furthermore, we show that the polybasic domain of Cdc11, in addition to the amphipathic helix of Cdc12, plays an essential role in supporting the membrane remodeling and curvature-sensing properties of yeast septins. Collectively, our work provides a framework for understanding the molecular mechanisms by which septins can support cellular functions intimately linked to membranes.
Contribution of the epididymis beyond fertilization: relevance of CRISP1 and CRISP3 for sperm DNA integrity and early embryo development
Authors: Sulzyk Valeria , Curci Ludmila , González Lucas N , Rebagliati Cid Abril , Weigel Muñoz Mariana , Cuasnicu Patricia S 
Published: March 2024

AbstractNumerous reports show that the epididymis plays a key role in the acquisition of sperm fertilizing ability but less information exists on its contribution to embryo development. Evidence from our laboratory showed that mammalian CRISP (Cysteine-Rich Secretory Proteins), known to be expressed in the epididymis, to regulate calcium (Ca2+) channels and to participate in fertilization, may also be relevant for embryo development. More specifically, we found that males with simultaneous mutations inCrisp1andCrisp3genes exhibited normalin vivofertilization but impaired embryo development. In the present work, aimed to investigate the mechanisms underlying this reproductive phenotype, we observed that embryo development failure was not due to delayed fertilization as no differences in sperm transport within the female tract nor inin vivofertilization were found shortly after mating. The observation that impaired embryo development was also found in eggs fertilized by epididymal sperm either after uterine insemination orin vitrofertilization, revealed that the defects were already present at epididymal level. Of note, eggs fertilizedin vitroby mutant sperm exhibited impaired meiotic resumption not due to defects in Ca2+oscillations during egg activation, prompting us to examine potential sperm DNA defects. Interestingly, DNA fragmentation was found in cauda but not caput epididymal mutant sperm revealing that DNA integrity defects appear during epididymal maturation. Moreover, exposure of control sperm to mutant epididymal fluid significantly increased DNA fragmentation, indicating the relevance of the luminal environment for sperm DNA integrity. The finding that incubation of sperm with control epididymal fluid in the presence of Ca2+also increased DNA fragmentation together with the higher intracellular Ca2+levels detected in mutant sperm supports a dysregulation of Ca2+homeostasis as the main responsible for DNA fragmentation and subsequent early development failure of mutant males. Together, our results support the contribution of the epididymis beyond fertilization, identifying CRISP1 and CRISP3 as novel male factors relevant for DNA integrity and early embryo development. Given the existence of human functional homologues of CRISP and the incidence of DNA fragmentation in infertile men, we believe these findings not only provide relevant information on the impact of epididymal factors on embryonic development but will also contribute to a better understanding, diagnosis and treatment of human infertility.