bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic correlations: exact and approximate methods for mutual information
Authors: Demirtaş Kemal , Erman Burak , Haliloğlu Türkan 
Published: February 2024

Abstract

Motivation
Proteins are dynamic entities that undergo conformational changes critical for their functions. Understanding the communication pathways and information transfer within proteins is crucial for elucidating allosteric interactions in their mechanisms. This study utilizes mutual information (MI) analysis to probe dynamic allostery. Using two cases, Ubiquitin and PLpro, we have evaluated the accuracy and limitations of different approximations including the exact anisotropic and isotropic models, multivariate Gaussian model, isotropic Gaussian model, and the Gaussian Network Model (GNM) in revealing allosteric interactions.

Results
Our findings emphasize the required trajectory length for capturing accurate mutual information profiles. Long molecular dynamics trajectories, 1 ms for Ubiquitin and 100 µs for PLpro are used as benchmarks, assuming they represent the ground truth. Trajectory lengths of approximately 5 µs for Ubiquitin and 1 µs for PLpro marked the onset of convergence, while the multivariate Gaussian model accurately captured mutual information with trajectories of 5 ns for Ubiquitin and 350 ns for PLpro. However, the isotropic Gaussian model is less successful in representing the anisotropic nature of protein dynamics, particularly in the case of PLpro, highlighting its limitations. The GNM, however, provides reasonable approximations of long-range information exchange as a minimalist network model based on a single crystal structure. Overall, the optimum trajectory lengths for effective Gaussian approximations of long-time dynamic behavior depend on the inherent dynamics within the protein's topology. The GNM, by showcasing dynamics across relatively diverse time scales, can be used either as a standalone method or to gauge the adequacy of MD simulation lengths.

Availability and implementation
Mutual information codes are available at https://github.com/kemaldemirtas/prc-MI.git.
Membrane inflammasome activation by choriodecidual Ureaplasma parvum infection without intra-amniotic infection in a Non-Human Primate model
Authors: Tripathy Sudeshna , Burd Irina , Kelleher Meredith A 
Published: February 2024

Abstract
Intrauterine infection is a significant cause of neonatal morbidity and mortality. Ureaplasma parvum is a microorganism commonly isolated from cases of preterm birth and preterm premature rupture of membranes (pPROM). However, the mechanisms of early stage ascending reproductive tract infection remain poorly understood. To examine inflammation in fetal (chorioamnionic) membranes we utilized a non-human primate (NHP) model of choriodecidual U. parvum infection. Eight chronically catheterized pregnant rhesus macaques underwent maternal–fetal catheterization surgery at ~105–112 days gestation and choriodecidual inoculation with U. parvum (105 CFU/mL, n =4) or sterile media (controls; n = 4) starting at 115–119 days, repeated at 5-day intervals until C-section at 136–140 days (term=167 days). The average inoculation to delivery interval was 21 days, and Ureaplasma infection of the amniotic fluid (AF) was undetectable in all animals. Choriodecidual Ureaplasma infection resulted in increased fetal membrane expression of MMP-9 and PTGS2, but did not result in preterm labor or increased concentrations of AF pro-inflammatory cytokines. However, membrane expression of inflammasome sensors, NLRP3, NLRC4, AIM2, and NOD2, and adaptor ASC (PYCARD) gene expression were significantly increased. Gene expression of IL-1β, IL-18, IL-18R1 , CASPASE-1, and pro-CASPASE-1 protein increased with Ureaplasma infection. Downstream inflammatory genes MYD88 and NFκB (Nuclear factor kappa-light-chain-enhancer of activated B cells) were also significantly upregulated. These results demonstrate that choriodecidual Ureaplasma infection, can cause activation of inflammasome complexes and pathways associated with pPROM and preterm labor prior to microbes being detectable in the AF.
Ethical considerations for artificial intelligence in dermatology: a scoping review
Authors: Gordon Emily R , Trager Megan H , Kontos Despina , Weng Chunhua , Geskin Larisa J , Dugdale Lydia S , Samie Faramarz H 
Published: February 2024

Abstract
The field of dermatology is experiencing the rapid deployment of artificial intelligence (AI), from mobile applications (apps) for skin cancer detection to large language models like ChatGPT that can answer generalist or specialist questions about skin diagnoses. With these new applications, ethical concerns have emerged. In this scoping review, we aimed to identify the applications of AI to the field of dermatology and to understand their ethical implications. We used a multifaceted search approach, searching PubMed, MEDLINE, Cochrane Library and Google Scholar for primary literature, following the PRISMA Extension for Scoping Reviews guidance. Our advanced query included terms related to dermatology, AI and ethical considerations. Our search yielded 202 papers. After initial screening, 68 studies were included. Thirty-two were related to clinical image analysis and raised ethical concerns for misdiagnosis, data security, privacy violations and replacement of dermatologist jobs. Seventeen discussed limited skin of colour representation in datasets leading to potential misdiagnosis in the general population. Nine articles about teledermatology raised ethical concerns, including the exacerbation of health disparities, lack of standardized regulations, informed consent for AI use and privacy challenges. Seven addressed inaccuracies in the responses of large language models. Seven examined attitudes toward and trust in AI, with most patients requesting supplemental assessment by a physician to ensure reliability and accountability. Benefits of AI integration into clinical practice include increased patient access, improved clinical decision-making, efficiency and many others. However, safeguards must be put in place to ensure the ethical application of AI.
Construction of triptycene molecular rotors with intermeshing arrangement and low rotational barrier
Authors: Furuta Tomoki , Oka Kouki , Tohnai Norimitsu 
Published: February 2024

Abstract
Molecular rotors are one of the building blocks of molecular machines and they are nano-sized with mechanically rotating moieties. Among them, intermeshing triptycenes with a gear-like skeleton allow the construction of a molecular rotor that transmits rotational motion. For triptycenes to mesh with each other without loss of rotation, intermeshing them in parallel and adjusting the distance between their axes to 8.1 Å are required. However, with conventional methods, because of the restrictions on bond lengths and atomic radii, achieving an ideal arrangement in which the triptycenes mesh in parallel at 8.1 Å has been difficult. In this work, we synthesized disulfonic acid containing a triptycene as a rotator and combined it with amines of 2 different steric factors (normal-amylamine [nAmA] and guanidine [Gu]), which allowed us to prepare organic salts with varying arrangements of triptycenes. In the organic salt with the planar amine (Gu), the crystal structure was close to the ideal intermeshing arrangement of the triptycene and the distance between their axes was 7.7 Å. The T1ρ 13C spin-lattice relaxation time using solid-state nuclear magnetic resonance (NMR) demonstrated that triptycene rotates efficiently at 24 kHz at 313 K with a low rotational barrier (10.9 kcal/mol) compared with non-intermeshing structures.
Eyes Wide Shut: A Cohort Study Questioning the Role of Fundoscopy in Infective Endocarditis Diagnosis
Authors: Stavropoulou Elisavet , Guery Benoit , Tzimas Georgios , Guex-Crosier Yan , Hoogewoud Florence , Tozzi Piergiorgio , Kirsch Matthias , Monney Pierre , Papadimitriou-Olivgeris Matthaios 
Published: February 2024

Abstract
In this retrospective/prospective study, we assessed the role of fundoscopy in 711 episodes with suspected infective endocarditis (IE); 238 (33%) had IE. Ocular embolic events (retinal emboli or chorioretinitis/endophthalmitis) and Roth spots were found in 37 (5%) and 34 (5%) episodes, respectively, but had no impact on IE diagnosis.
Tobacco Smoke Exposure in Early Childhood and Later Risk of Inflammatory Bowel Disease: A Scandinavian Birth Cohort Study
Authors: Sigvardsson Ida , Ludvigsson Johnny , Andersson Björn , Størdal Ketil , Mårild Karl 
Published: February 2024

Abstract

Objectives
To examine the association between early-life smoking exposure and later risk of inflammatory bowel disease [IBD].

Methods
We followed 115663 participants from the Norwegian Mother, Father and Child [MoBa] and All Babies in Southeast Sweden [ABIS] cohorts from birth [1997–2009] through 2021. IBD was identified through national patient registers. Validated questionnaire data defined maternal smoking during pregnancy, maternal environmental tobacco smoke [ETS] exposure during pregnancy, and child ETS exposure by ages 12 and 36 months. Cox regression was used to estimate adjusted hazard ratios [aHRs] for sex, maternal age, education level, parental IBD, and origin. Cohort-specific estimates were pooled using a random-effects model.

Results
During 1 987 430 person-years of follow-up, 444 participants developed IBD [ABIS, 112; MoBa, 332]. Any vs no maternal smoking during pregnancy yielded a pooled aHR of 1.30 [95% CI = 0.97–1.74] for offspring IBD. Higher level of maternal smoking during pregnancy (compared with no smoking, average ≥6 cigarettes/day: pooled aHR = 1.60 [95% CI = 1.08–2.38]) was associated with offspring IBD, whereas a lower smoking level was not (average 1–5 cigarettes/day: pooled aHR = 1.09 [95% CI = 0.73–1.64]). Child ETS exposure in the first year of life was associated with later IBD (any vs no ETS, pooled aHR = 1.32 [95% CI = 1.03–1.69]). Estimates observed for child ETS exposure by 36 months were similar but not statistically significant.

Conclusions
In this prospective Scandinavian cohort study, children exposed to higher levels of maternal smoking during pregnancy or ETS during the first year of life were at increased risk of later IBD.
Transcatheter aortic valve replacement planning with cardiac computed tomography in quadricuspid aortic valve stenosis: a case series
Authors: Aquino-Bruno Heberto , Muratalla-González Roberto , Garcia-Garcia Juan F , Triano-Doroteo José L , Rivera Kevin Felix , Balcarcel Gerardo Carreon , Navarrete-Osuna Marisol 
Published: February 2024

Abstract

Background
The presence of severe aortic stenosis in quadricuspid aortic valve (QAV) is an extremely rare combination, and it is unknown whether transcatheter aortic valve replacement (TAVR) is a safe option due to the low incidence.

Case summary
We present two patients diagnosed with severe aortic stenosis with QAV morphology type 1 (Nakamura classification). All patients presented to our hospital for evaluation because of worsening functional class, dyspnoea, or syncope. During tomographic planning, the aortic annulus was measured at the level of the deepest sinus for the selection of the number of devices. Due to the presence of four cusps, the smallest cusp was excluded, and three sinuses were virtualized for placement of the pigtail catheter during the procedure. Without complications, a 23 mm Edwards SAPIEN 3 was deployed through the femoral artery in both patients. Control aortography showed no valve leakage or regurgitation.

Discussion
In patients with QAV and aortic stenosis undergoing TAVR, similar to the tricuspid valve, tomographic planning can be used to ensure the success of the procedure. However, unlike the tricuspid valve, where the selection of the device number is based on the measurements of the aortic annulus at the level of the non-coronary sinus, in these QAV cases, we perform the measurements at the level of the deepest aortic sinus (right coronary sinus).
Using natural language processing for automated classification of disease and to identify misclassified ICD codes in cardiac disease
Authors: Falter Maarten , Godderis Dries , Scherrenberg Martijn , Kizilkilic Sevda Ece , Xu Linqi , Mertens Marc , Jansen Jan , Legroux Pascal , Kindermans Hanne , Sinnaeve Peter , Neven Frank , Dendale Paul 
Published: February 2024

Abstract

Aims
ICD codes are used for classification of hospitalizations. The codes are used for administrative, financial, and research purposes. It is known, however, that errors occur. Natural language processing (NLP) offers promising solutions for optimizing the process. To investigate methods for automatic classification of disease in unstructured medical records using NLP and to compare these to conventional ICD coding.

Methods and results
Two datasets were used: the open-source Medical Information Mart for Intensive Care (MIMIC)-III dataset (n = 55.177) and a dataset from a hospital in Belgium (n = 12.706). Automated searches using NLP algorithms were performed for the diagnoses ‘atrial fibrillation (AF)’ and ‘heart failure (HF)’. Four methods were used: rule-based search, logistic regression, term frequency-inverse document frequency (TF-IDF), Extreme Gradient Boosting (XGBoost), and Bio-Bidirectional Encoder Representations from Transformers (BioBERT). All algorithms were developed on the MIMIC-III dataset. The best performing algorithm was then deployed on the Belgian dataset. After preprocessing a total of 1438 reports was retained in the Belgian dataset. XGBoost on TF-IDF matrix resulted in an accuracy of 0.94 and 0.92 for AF and HF, respectively. There were 211 mismatches between algorithm and ICD codes. One hundred and three were due to a difference in data availability or differing definitions. In the remaining 108 mismatches, 70% were due to incorrect labelling by the algorithm and 30% were due to erroneous ICD coding (2% of total hospitalizations).

Conclusion
A newly developed NLP algorithm attained a high accuracy for classifying disease in medical records. XGBoost outperformed the deep learning technique BioBERT. NLP algorithms could be used to identify ICD-coding errors and optimize and support the ICD-coding process.
Recombinant Full-length Plasmodium falciparum Circumsporozoite Protein–Based Vaccine Adjuvanted With Glucopyranosyl Lipid A–Liposome Quillaja saponaria 21: Results of Phase 1 Testing With Malaria Challenge
Authors: Friedman-Klabanoff DeAnna J , Berry Andrea A , Travassos Mark A , Shriver Mallory , Cox Catherine , Butts Jessica , Lundeen Jordan S , Strauss Kathleen A , Joshi Sudhaunshu , Shrestha Biraj , Mo Annie X , Nomicos Effie Y H , Deye Gregory A , Regules Jason A , Bergmann-Leitner Elke S , Pasetti Marcela F , Laurens Matthew B 
Published: February 2024

Abstract

Background
Malaria is preventable yet causes &gt;600 000 deaths annually. RTS,S, the first marketed malaria vaccine, has modest efficacy, but improvements are needed for eradication.

Methods
We conducted an open-label, dose escalation phase 1 study of a full-length recombinant circumsporozoite protein vaccine (rCSP) administered with adjuvant glucopyranosyl lipid A–liposome Quillaja saponaria 21 formulation (GLA-LSQ) on days 1, 29, and 85 or 1 and 490 to healthy, malaria-naive adults. The primary end points were safety and reactogenicity. The secondary end points were antibody responses and Plasmodium falciparum parasitemia after homologous controlled human malaria infection.

Results
Participants were enrolled into 4 groups receiving rCSP/GLA-LSQ: 10 µg × 3 (n = 20), 30 µg × 3 (n = 10), 60 µg × 3 (n = 10), or 60 µg × 2 (n = 9); 10 participants received 30 µg rCSP alone × 3, and there were 6 infectivity controls. Participants experienced no serious adverse events. Rates of solicited and unsolicited adverse events were similar among groups. All 26 participants who underwent controlled human malaria infection 28 days after final vaccinations developed malaria. Increasing vaccine doses induced higher immunoglobulin G titers but did not achieve previously established RTS,S benchmarks.

Conclusions
rCSP/GLA-LSQ had favorable safety results. However, tested regimens did not induce protective immunity. Further investigation could assess whether adjuvant or schedule adjustments improve efficacy.

Clinical Trials Registration
NCT03589794
Comparison of prebiotic candidates in ulcerative colitis using an in vitro fermentation model
Authors: Kennedy James M , De Silva Aminda , Walton Gemma E , Poveda Carlos , Gibson Glenn R 
Published: February 2024

Abstract

Aims
This study explored the effect of three different prebiotics, the human milk oligosaccharide 2′-fucosyllactose (2′-FL), an oligofructose-enriched inulin (fructo-oligosaccharide, or FOS), and a galacto-oligosaccaride (GOS) mixture, on the faecal microbiota from patients with ulcerative colitis (UC) using in vitro batch culture fermentation models. Changes in bacterial groups and short-chain fatty acid (SCFA) production were compared.

Methods and results
In vitro pH controlled batch culture fermentation was carried out over 48 h on samples from three healthy controls and three patients with active UC. Four vessels were run, one negative control and one for each of the prebiotic substrates. Bacterial enumeration was carried out using fluorescence in situ hybridization with flow cytometry. SCFA quantification was performed using gas chromatography mass spectrometry. All substrates had a positive effect on the gut microbiota and led to significant increases in total SCFA and propionate concentrations at 48 h. 2′-FL was the only substrate to significantly increase acetate and led to the greatest increase in total SCFA concentration at 48 h. 2′-FL best suppressed Desulfovibrio spp., a pathogen associated with UC.

Conclusions
2′FL, FOS, and GOS all significantly improved the gut microbiota in this in vitro study and also led to increased SCFA.
Cumulated time to chart closure: a novel electronic health record-derived metric associated with clinician burnout
Authors: Shah Madhura , De Arrigunaga Sofia , Forman Leah S , West Matthew , Rowe Susannah G , Mishuris Rebecca G 
Published: February 2024

Abstract

Objective
We sought to determine whether average cumulated time to chart closure (CTCC), a novel construct to measure clinician workload burden, and electronic health record (EHR) measures were associated with a validated measure of burnout.

Materials and methods
Physicians at a large academic institution participated in a well-being survey that was linked to their EHR use data. CTCC was defined as the average time from the start of patient encounters to chart closure over a set of encounters. Established EHR use measures including daily total time in the EHR (EHR-Time8), time in the EHR outside scheduled hours, work outside of work (WOW8), and time spent on inbox (IB-Time8) were calculated. We examined the relationship between CTCC, EHR use metrics, and burnout using descriptive statistics and adjusted logistic regression models.

Results
We included data from 305 attendings, encompassing 242 432 ambulatory encounters (2021). Among them, 42% (128 physicians) experienced burnout. The median CTCC for all clinicians was 32.5 h. Unadjusted analyses revealed significant associations between CTCC, WOW8, IB-Time8, and burnout. In a final adjusted model, only CTCC remained statistically significant with an odds ratio estimate of 1.42 (95% CI, 1.00-2.01).

Discussion
These results suggest that CTCC is predictive of burnout and that purely measuring duration of interaction with the EHR itself is not sufficient to capture burnout.

Conclusion
Workload burden as manifested by average CTCC has the potential to be a practical, quantifiable measure that will allow for identification of clinicians at risk of burnout and to assess the success of interventions designed to address burnout.
UDGAN: A new urban design inspiration approach driven by using generative adversarial networks
Authors: Gan Wei , Zhao Zichen , Wang Yuankai , Zou Yixuan , Zhou Shiqi , Wu Zhiqiang 
Published: February 2024

Abstract
The morphological design of urban space affects the quality of the environment. The traditional experience-based design approach was greatly improved by introducing computational design tools. However, the existing urban design tools are mostly developed on pre-set rules or given targets, which have few contributions to enhance creativity or generate inspiring schemes. Therefore, this paper proposes a new computational urban design approach named UDGAN, integrating generative adversarial networks (GANs) and multi-objective optimization algorithms. This model utilizes urban design scheme plans over the past 20 years from a particular designer as training datasets. Four preference models were trained to autonomously generate stylized urban design schemes. Eight morphological parameters were used to analyze the model performance by comparing generated results with the ground truth. This GAN-based surrogate approach is combined with a morphological indicator alignment process using multi-objective optimization model to obtain better results. The result shows that the R2 predicted by the improved Pix2Pix model reaches 0.798, and the similarity of the generated results can be stably distributed between 0.7 and 0.8, so the design scheme of this preferred style can be effectively learned. At the same time, the pre-trained model greatly reduces the time consumption of the design scheme generation, taking 5 min approximately to complete a generation process. This approach quickly generated the design scheme with preferred features, supporting the designer with creativity and greatly saving the time of design creation, transforming computational design into an inspiration-driven process.
Evolution of intermediate latency strategies in seasonal parasites
Authors: MacDonald Hannelore , Brisson Dustin 
Published: February 2024

Abstract
Traditional mechanistic trade-offs between transmission and parasite latency period length are foundational for nearly all theories on the evolution of parasite life-history strategies. Prior theoretical studies demonstrate that seasonal host activity can generate a trade-off for obligate-host killer parasites that selects for intermediate latency periods in the absence of a mechanistic trade-off between transmission and latency period lengths. Extensions of these studies predict that host seasonal patterns can lead to evolutionary bistability for obligate-host killer parasites in which two evolutionarily stable strategies, a shorter and longer latency period, are possible. Here we demonstrate that these conclusions from previously published studies hold for non-obligate host killer parasites. That is, seasonal host activity can select for intermediate parasite latency periods for non-obligate killer parasites in the absence of a trade-off between transmission and latency period length and can maintain multiple evolutionarily stable parasite life-history strategies. These results reinforce the hypothesis that host seasonal activity can act as a major selective force on parasite life-history evolution by extending the narrower prior theory to encompass a greater range of disease systems.