bluuebunny/crossref_metadata_2025_split huggingface dataset:
Organizational Structure and Pricing: Evidence from a Large U.S. Airline
Authors: Hortaçsu Ali , Natan Olivia R , Parsley Hayden , Schwieg Timothy , Williams Kevin R 
Published: September 2023

Abstract
Firms facing complex objectives often decompose the problems they face, delegating different parts of the decision to distinct subunits. Using comprehensive data and internal models from a large U.S. airline, we establish that airline pricing is not well approximated by a model of the firm as a unitary decision maker. We show that observed prices, however, can be rationalized by accounting for organizational structure and for the decisions by departments that are tasked with supplying inputs to the observed pricing heuristic. Simulating the prices the firm would charge if it were a rational, unitary decision maker results in lower welfare than we estimate under observed practices. Finally, we discuss why counterfactual estimates of welfare and market power may be biased if prices are set through decomposition, but we instead assume that they are set by unitary decision makers.
Targeting enhanced neutralizing antibody responses via increased germinal center activity: early-phase vaccine trials with novel clinical designs
Authors: Hahn William O. , Hill Joshua A. , Kublin James G. 
Published: September 2023

Purpose of review
Recent advances in the understanding of the difficult immunologic requirements for the induction of broadly neutralizing antibodies for HIV have spurred interest in optimizing vaccine approaches intended to stimulate a robust germinal center reaction. In preclinical models, techniques to optimize the germinal center response have included alterations in the timing, dose, and delivery method of immunogens and have resulted in substantially enhanced germinal center responses in lymph nodes and neutralizing antibodies in serum. One of the most promising approaches involves splitting the initial dose of vaccine into a series of gradual escalating doses administration (“fractional escalating doses”). In principle, these techniques may have broad implications for vaccines targeting a robust antibody response.

Recent findings
We review the upcoming vaccine trials that will test these concepts in clinical practice. The trials include both HIV and non-HIV immunogens, and will involve testing these concepts in both healthy adults and immunocompromised persons.

Summary
There are multiple trials that will test whether techniques to alter vaccine delivery such as fractional escalating doses enhances immunologic outcomes.
Designing the coronary artery bypass surgery operation of the future
Authors: Ruel Marc 
Published: September 2023

Purpose of review
This article discusses current shortcomings in coronary artery bypass surgery and ways to overcome them.

Recent findings
Minimally invasive coronary bypass surgery, robotic coronary bypass, and hybrid approaches aim to avoid sternotomy, employ arterial grafts, and minimize the use of cardiopulmonary bypass. Other considerations such as bypass graft validation, the optimization of guideline-directed medical therapy, and the development of coronary surgery specialists are also crucial to further the benefits of coronary artery bypass grafting on future patients.

Summary
Coronary artery bypass grafting must become less invasive, be better validated, and be carried out with an even higher emphasis on quality, including graft validation and preoperative/postoperative optimization, if it is to remain the best treatment for advanced, severe coronary artery disease.
Advances in cardiac pacing with leadless pacemakers and conduction system pacing
Authors: Somani Sulaiman , Rogers Albert J. 
Published: September 2023

Purpose of review
The field of cardiac pacing has undergone significant evolution with the introduction and adoption of conduction system pacing (CSP) and leadless pacemakers (LLPMs). These innovations provide benefits over conventional pacing methods including avoiding lead related complications and achieving more physiological cardiac activation. This review critically assesses the latest advancements in CSP and LLPMs, including their benefits, challenges, and potential for future growth.

Recent findings
CSP, especially of the left bundle branch area, enhances ventricular depolarization and cardiac mechanics. Recent studies show CSP to be favorable over traditional pacing in various patient populations, with an increase in its global adoption. Nevertheless, challenges related to lead placement and long-term maintenance persist. Meanwhile, LLPMs have emerged in response to complications from conventional pacemaker leads. Two main types, Aveir and Micra, have demonstrated improved outcomes and adoption over time. The incorporation of new technologies allows LLPMs to cater to broader patient groups, and their integration with CSP techniques offers exciting potential.

Summary
The advancements in CSP and LLPMs present a transformative shift in cardiac pacing, with evidence pointing towards enhanced clinical outcomes and reduced complications. Future innovations and research are likely to further elevate the clinical impact of these technologies, ensuring improved patient care for those with conduction system disorders.
Perinatal and Other Risk Factors for Common Infections in Infancy: A Prospective Cohort Study
Authors: Hyvönen Sanni , Tapiainen Terhi , Pokka Tytti , Solasaari Terhi , Korpela Katri , de Vos Willem M. , Salonen Anne , Kolho Kaija-Leena 
Published: September 2023

Objective:
Limited data from prospective cohort studies in high-income countries are available on the perinatal risk factors for common infections in children. Our hypothesis was that perinatal factors may be risk factors for infectious episodes during the first year of life.

Methods:
In this prospective Health and Early Life Microbiota birth cohort study of full-term infants (n = 1052) born in 2016–2018, the number and duration of infection episodes were collected online at weekly to monthly intervals. In a multivariate regression model, the main exposures were perinatal factors such as mode of delivery and intrapartum antibiotics. Environmental factors were additional exposures. The outcomes were the number and duration of infectious episodes in the first year of life.

Results:
The mean number of infection episodes was 4.2 (2.9 SD). The mean duration of infection symptoms was 44 days (40 SD). Upper respiratory infections accounted for 83% of the episodes (3674/4455). Perinatal factors were not associated with the number nor the duration of infection episodes, but cesarean section was associated with an increased occurrence of urinary tract infections in infancy [adjusted odds ratio (aOR): 3.6; 95% confidence interval (CI): 1.13–11.1]. Of the additional exposures male sex (aOR: 1.1; 95% CI: 1.0–1.2) and the presence of siblings (aOR: 1.3; 95% CI: 1.2–1.4) were associated with the number of infection episodes.

Conclusions:
This prospective cohort study showed that perinatal factors, mode of delivery and intrapartum antibiotics were not associated with the risk of common infections in infancy, but cesarean delivery was associated with a risk of urinary tract infections.
Large-scale momentary brain co-activation patterns are associated with hyperalgesia and mediate focal neurochemistry and cross-network functional connectivity in fibromyalgia
Authors: Mawla Ishtiaq , Huang Zirui , Kaplan Chelsea M. , Ichesco Eric , Waller Noah , Larkin Tony E. , Zöllner Helge J. , Edden Richard A.E. , Harte Steven E. , Clauw Daniel J. , Mashour George A. , Napadow Vitaly , Harris Richard E. 
Published: September 2023

Abstract
Fibromyalgia has been characterized by augmented cross-network functional communication between the brain's sensorimotor, default mode, and attentional (salience/ventral and dorsal) networks. However, the underlying mechanisms of these aberrant communication patterns are unknown. In this study, we sought to understand large-scale topographic patterns at instantaneous timepoints, known as co-activation patterns (CAPs). We found that a sustained pressure pain challenge temporally modulated the occurrence of CAPs. Using proton magnetic resonance spectroscopy, we found that greater basal excitatory over inhibitory neurotransmitter levels within the anterior insula orchestrated higher cross-network connectivity between the anterior insula and the default mode network through lower occurrence of a CAP encompassing the attentional networks during sustained pain. Moreover, we found that hyperalgesia in fibromyalgia was mediated through increased occurrence of a CAP encompassing the sensorimotor network during sustained pain. In conclusion, this study elucidates the role of momentary large-scale topographic brain patterns in shaping noxious information in patients with fibromyalgia, while laying the groundwork for using precise spatiotemporal dynamics of the brain for the potential development of therapeutics.
Small intestinal bacterial overgrowth: current update
Authors: Zafar Hammad , Jimenez Brenda , Schneider Alison 
Published: September 2023

Purpose of review
This article aims to provide an up-to-date review of small intestinal bacterial overgrowth (SIBO), including etiology and risk factors, clinical manifestations, diagnostic evaluation for suspected SIBO, and therapeutic options.

Recent findings
Recent advances in breath testing, capsule and urine-based testing have opened new avenues and improved diagnostic yield of SIBO. Nonantibiotic-based treatment strategies have shown promising results in initial trials.

Summary
Small intestinal bacterial overgrowth (SIBO) is a condition defined by the excess bacteria or changes in bacterial composition of the small intestine. These are associated with various gastrointestinal (GI) symptoms such as bloating, abdominal distension, diarrhea, nutrient deficiencies, and even frank weight loss. Small bowel jejunal aspirate of >105CFU/ml has traditionally been considered the gold standard for diagnosis. Glucose and lactulose breath testing have become more common in clinical practice as they are noninvasive, easily accessible, and have lower cost. Treatment focuses on the eradication of excess bacteria in the small bowel and is traditionally done with the use of oral antibiotics. Other emerging therapies may include probiotics, diet manipulation, and prokinetic agents.
Pediatric tracheostomy decannulation: what's the evidence?
Authors: Raynor Tiffany , Bedwell Joshua 
Published: September 2023

Purpose of review
Pediatric decannulation failure can be associated with large morbidity and mortality, yet there are no published evidence-based guidelines for pediatric tracheostomy decannulation. Tracheostomy is frequently performed in medically complex children in whom it can be difficult to predict when and how to safely decannulate.

Recent findings
Published studies regarding pediatric decannulation are limited to reviews and case series from single institutions, with varying populations, indications for tracheostomy, and institutional resources. This article will provide a review of published decannulation protocols over the past 10 years. Endoscopic airway evaluation is required to assess the patency of the airway and address any airway obstruction prior to decannulation. There is considerable variability in tracheostomy tube modification between published protocols, though the majority support a capping trial and downsizing of the tracheostomy tube to facilitate capping. Most protocols include overnight capping in a monitored setting prior to decannulation with observation ranging from 24 to 48 h after decannulation. There is debate regarding which patients should have capped polysomnography (PSG) prior to decannulation, as this exam is resource-intensive and may not be widely available. Persistent tracheocutaneous fistulae are common following decannulation. Excision of the fistula tract with healing by secondary intention has a lower reported operative time, overall complication rate, and postoperative length of stay.

Summary
Pediatric decannulation should occur in a stepwise process. The ideal decannulation protocol should be safe and expedient, without utilizing excessive healthcare resources. There may be variability in protocols based on patient population or institutional resources, but an explicitly described protocol within each institution is critical to consistent care and quality improvement over time. Further research is needed to identify selection criteria for who would most benefit from PSG prior to decannulation to guide allocation of this limited resource.
Circulating Tumor DNA Is an Accurate Diagnostic Tool and Strong Prognostic Marker in Pancreatic Cancer
Authors: Sellahewa Rav , Moghaddam Samar Masoumi , Lundy Joanne , Jenkins Brendan J. , Croagh Daniel 
Published: September 2023

Objective
The objectives of the study are to investigate the sensitivity and specificity of circulating tumor DNA (ctDNA) for the diagnosis of pancreatic cancer and to assess the utility of ctDNA as a prognostic marker in this disease.

Methods
Cell-free DNA was extracted from plasma of patients who underwent endoscopic ultrasound fine-needle aspiration or surgical resections for pancreatic cancer. The cell-free DNA was then analyzed using droplet digital polymerase chain reaction for KRAS G12/13 mutations. Eighty-one patients with pancreatic cancer and 30 patients with benign pancreatic disease were analyzed.

Results
ctDNA KRAS G12/13 mutations were detected in 63% of all patients with pancreatic cancer and in 76% of those patients who also had KRAS G12/13 mutations detected in the pancreatic primary. Specificity and tissue concordance were both 100%. Circulating tumor DNA corresponded with tumor size and stage, and high ctDNA was associated with significantly worse prognosis on both univariate and multivariate testing.

Conclusion
Our study shows that ctDNA is an accurate diagnostic tool and strong prognostic marker in patients with pancreatic cancer. The continued investigation of ctDNA will enable its implementation in clinical practice to optimize the care and survival outcomes of patients with pancreatic cancer.
Somatic mutations reveal hyperactive Notch signaling and racial disparities in prurigo nodularis
Authors: Rajeh Ahmad , Cornman Hannah L. , Gupta Anuj , Szeto Mindy D. , Kambala Anusha , Oladipo Olusola , Parthasarathy Varsha , Deng Junwen , Wheelan Sarah , Pritchard Thomas , Kwatra Madan M. , Semenov Yevgeniy R. , Gusev Alexander , Yegnasubramanian Srinivasan , Kwatra Shawn G. 
Published: September 2023

AbstractPrurigo nodularis (PN) is a chronic inflammatory skin disease that disproportionately affects African Americans and is characterized by pruritic skin nodules of unknown etiology. Little is known about genetic alterations in PN pathogenesis, especially relating to somatic events which are often implicated in inflammatory conditions. We thus performed whole-exome sequencing on 54 lesional and nonlesional skin biopsies from 17 PN patients and 10 atopic dermatitis (AD) patients for comparison. Somatic mutational analysis revealed that PN lesional skin harbors pervasive somatic mutations in fibrotic, neurotropic, and cancer-associated genes. Nonsynonymous mutations were most frequent inNOTCH1and the Notch signaling pathway, a regulator of cellular proliferation and tissue fibrosis, andNOTCH1mutations were absent in AD. Somatic copy-number analysis, combined with expression data, showed that recurrently deleted and downregulated genes in PN lesional skin are associated with axonal guidance and extension. Follow-up immunofluorescence validation demonstrated increasedNOTCH1expression in PN lesional skin fibroblasts and increased Notch signaling in PN lesional dermis. Finally, multi-center data revealed a significantly increased risk ofNOTCH1-associated diseases in PN patients. In characterizing the somatic landscape of PN, we uncover novel insights into its pathophysiology and identify a role for dysregulated Notch signaling in PN.
Separate and overlapping mechanisms of statistical regularities and salience processing in the occipital cortex and dorsal attention network
Authors: Beffara Bertrand , Hadj-Bouziane Fadila , Ben Hamed Suliann , Boehler C. Nico , Chelazzi Leonardo , Santandrea Elisa , Macaluso Emiliano 
Published: September 2023

ABSTRACTAttention selects behaviorally relevant inputs for in-depth processing. Beside the role of traditional signals related to goal-directed and stimulus-driven control, a debate exists regarding the mechanisms governing the effect of statistical regularities on attentional selection, and how these are integrated with other control signals. Using a visuo-spatial search task under fMRI, we tested the joint effects of statistical regularities and stimulus-driven salience. We found that both types of signals modulated occipital activity in a spatially-specific manner. Salience acted primarily by reducing the attention bias towards the target location when associated with irrelevant distractors, while statistical regularities reduced this attention bias when the target was presented at a low probability location, particularly at the lower levels of the visual hierarchy. In addition, we found that both statistical regularities and salience activated the dorsal frontoparietal network. Additional exploratory analyses of functional connectivity revealed that only statistical regularities modulated the inter-regional coupling between the posterior parietal cortex and the occipital cortex. These results show that statistical regularities and salience signals are both spatially represented at the occipital level, but that their integration into attentional processing priorities relies on dissociable brain mechanisms.
Scalable joint non-negative matrix factorisation for paired single cell gene expression and chromatin accessibility data
Authors: Morgans William , Sharrocks Andrew D. , Iqbal Mudassar 
Published: September 2023

Single cell multi-modal technologies provide powerful means to simultaneously profile components of the gene regulatory path-ways of individual cells. These are now being employed to study gene regulatory mechanisms in a variety of biological systems. Tailored computational methods for integration and analysis of these data are much-needed with desirable properties in terms of efficiency -to cope with high dimensionality of the data, inter-pretability -for downstream biological discovery and hypothesis generation, and flexibility -to be able to easily incorporate future modalities. Existing methods cover some but not all of the desirable properties for effective integration of these data.Here we present a highly efficient method, intNMF, for representation and integration of single cell multi-modal data using joint non-negative matrix factorisation which can facilitate discovery of linked regulatory topics in each modality. We provide thorough benchmarking using large publicly available datasets against five popular existing methods. intNMF performs comparably against the current state-of-the-art, and provides advantages in terms of computational efficiency and interpretability of discovered regulatory topics in the original feature space. We illustrate this enhanced interpretability in providing insights into cell state changes associated with Alzheimer’s disease. int-NMF is available as a Python package with extensive documentation and use-cases athttps://github.com/wmorgans/quick_intNMF
Glacier extinction homogenizes functional diversity
Authors: Khelidj Nora , Caccianiga Marco , Cerabolini Bruno E.L. , Tampucci Duccio , Losapio Gianalberto 
Published: September 2023

QuestionsThe disappearance of glaciers threatens biodiversity and the functioning of ecosystems. To date, questions remain about the response of functional diversity to glacier extinction and its potential for adaptation to climate change. How does glacier retreat and extinction affect plant functional diversity? How do mean and variation of plant traits change with glacier retreat and extinction?LocationFour glacier ecosystems in Italian Alps. Plant communities spanning 0 to ca 5,000 years on average after glacier retreat.MethodsWe quantify how glacier retreat affects functional diversity of plant communities analysing twelve functional traits of 117 plant species across 170 plots. First, we addressed the impact of glacier retreat on functional divergence and functional homogeneity, analysing both trait average and trait variation. Next, we explored how biodiversity (i.e., plant species richness) influenced functional diversity and how glacier retreat affected such relationship. Finally, we explored the effects of glacier retreat on mean and variation of single traits associated to carbon and nitrogen cycling and resource allocation.ResultsGlacier retreat homogenizes functional diversity by reducing trait variation and making communities more functionally similar. While biodiversity positively contributes to trait heterogeneity, glacier retreat erodes the support of species richness to functional diversity. We also show how glacier extinction has medium to large negative effects on the average and variation of key functional traits associated to carbon economy, but small positive effects on leaf nitrogen content.ConclusionsOur results demonstrate the pervasive impact of glacier extinction on the functioning of plant communities. We stress that functional diversity and trait variation should be the focus of adaptation and mitigation actions.
Context-aware single-cell multiome approach identified cell-type specific lung cancer susceptibility genes
Authors: Long Erping , Yin Jinhu , Shin Ju Hye , Li Yuyan , Kane Alexander , Patel Harsh , Luong Thong , Xia Jun , Han Younghun , Byun Jinyoung , Zhang Tongwu , Zhao Wei , Landi Maria Teresa , Rothman Nathaniel , Lan Qing , Chang Yoon Soo , Yu Fulong , Amos Christopher , Shi Jianxin , Lee Jin Gu , Kim Eun Young , Choi Jiyeon 
Published: September 2023

SummaryGenome-wide association studies (GWAS) identified over fifty loci associated with lung cancer risk. However, the genetic mechanisms and target genes underlying these loci are largely unknown, as most risk-associated-variants might regulate gene expression in a context-specific manner. Here, we generated a barcode-shared transcriptome and chromatin accessibility map of 117,911 human lung cells from age/sex-matched ever- and never-smokers to profile context-specific gene regulation. Accessible chromatin peak detection identified cell-type-specific candidatecis-regulatory elements (cCREs) from each lung cell type. Colocalization of lung cancer candidate causal variants (CCVs) with these cCREs prioritized the variants for 68% of the GWAS loci, a subset of which was also supported by transcription factor abundance and footprinting. cCRE colocalization and single-cell based trait relevance score nominated epithelial and immune cells as the main cell groups contributing to lung cancer susceptibility. Notably, cCREs of rare proliferating epithelial cell types, such as AT2-proliferating (0.13%) and basal cells (1.8%), overlapped with CCVs, including those inTERT. A multi-level cCRE-gene linking system identified candidate susceptibility genes from 57% of lung cancer loci, including those not detected in tissue- or cell-line-based approaches. cCRE-gene linkage uncovered that adjacent genes expressed in different cell types are correlated with distinct subsets of coinherited CCVs, includingJAMLandMPZL3at the 11q23.3 locus. Our data revealed the cell types and contexts where the lung cancer susceptibility genes are functional.