bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crohn’s Disease Phenotypes and Associations With Comorbidities, Surgery Risk, Medications and Nonmedication Approaches: The MAGIC in IMAGINE Study
Authors: Bernstein Charles N , Panaccione Remo , Nugent Zoann , Marshall Deborah A , Kaplan Gilaad G , Vanner Stephen , Dieleman Levinus A , Graff Lesley A , Otley Anthony , Jones Jennifer , Buresi Michelle , Murthy Sanjay , Borgaonkar Mark , Bressler Brian , Bitton Alain , Croitoru Kenneth , Sidani Sacha , Fernandes Aida , Moayyedi Paul 
Published: March 2024

Abstract

Background
We aimed to establish a cohort of persons with Crohn’s disease (CD) enrolled from 14 Canadian centers to describe the contemporary presentation of CD in Canada.

Methods
All enrollees were at least 18 years old and underwent chart review for phenotype documentation by Montreal Classification at time of enrollment, comorbidities, inflammatory bowel disease (IBD) and other surgeries, and use IBD and other therapies.

Results
Of 2112 adults, 59% were female, and the mean age was 44.1 (+/-14.9SD) years. The phenotype distribution was B1 = 50.4%, B2 = 22.4%, B3 = 17.3%, and missing information = 9.9%. Perineal disease was present in 14.2%. Pertaining to disease location, 35.2% of patients had disease in L1, 16.8% in L2, 48% in L3, and 0.4% in L4. There was no difference in phenotype by gender, anxiety score, depression score. Disease duration was significantly different depending on disease behavior type (B1 = 12.2 ± 10.1; B2 = 19.4 ± 12.9; B3 = 18.9 ± 11.8, P &lt; .0001). Isolated colonic disease was much less likely to be fibrostenotic or penetrating than inflammatory disease. Penetrating disease was more likely to be associated with ileocolonic location than other locations. Perineal disease was most commonly seen in persons with B3 disease behavior (24%) than other behaviors (11% B1; 20% B2 disease, P &lt; .0001) and more likely to be seen in ileocolonic disease (L3;19%) vs L2 (17%) and L1 (11%; P &lt; .0001). Surgery related to IBD occurred across each behavior types at the following rates: B1 = 23%, B2 = 64%, and B3 = 74%. Inflammatory bowel disease–related surgery rates by location of disease were L1 = 48%, L2 = 21%, and L3 = 51%.

Conclusions
In exploring this large contemporary CD cohort we have determined that inflammatory disease is the main CD phenotype in Canada and that CD-related surgery remains very common.
Accurate, Robust, and Scalable Machine Abstraction of Mayo Endoscopic Subscores From Colonoscopy Reports
Authors: Silverman Anna L , Bhasuran Balu , Mosenia Arman , Yasini Fatema , Ramasamy Gokul , Banerjee Imon , Gupta Saransh , Mardirossian Taline , Narain Rohan , Sewell Justin , Butte Atul J , Rudrapatna Vivek A 
Published: March 2024

Abstract

Background
The Mayo endoscopic subscore (MES) is an important quantitative measure of disease activity in ulcerative colitis. Colonoscopy reports in routine clinical care usually characterize ulcerative colitis disease activity using free text description, limiting their utility for clinical research and quality improvement. We sought to develop algorithms to classify colonoscopy reports according to their MES.

Methods
We annotated 500 colonoscopy reports from 2 health systems. We trained and evaluated 4 classes of algorithms. Our primary outcome was accuracy in identifying scorable reports (binary) and assigning an MES (ordinal). Secondary outcomes included learning efficiency, generalizability, and fairness.

Results
Automated machine learning models achieved 98% and 97% accuracy on the binary and ordinal prediction tasks, outperforming other models. Binary models trained on the University of California, San Francisco data alone maintained accuracy (96%) on validation data from Zuckerberg San Francisco General. When using 80% of the training data, models remained accurate for the binary task (97% [n = 320]) but lost accuracy on the ordinal task (67% [n = 194]). We found no evidence of bias by gender (P = .65) or area deprivation index (P = .80).

Conclusions
We derived a highly accurate pair of models capable of classifying reports by their MES and recognizing when to abstain from prediction. Our models were generalizable on outside institution validation. There was no evidence of algorithmic bias. Our methods have the potential to enable retrospective studies of treatment effectiveness, prospective identification of patients meeting study criteria, and quality improvement efforts in inflammatory bowel diseases.
A systems framework for investigating the roles of multiple transporters and their impact on drug resistance
Authors: di San Germano Manfredi , Krishnan J 
Published: March 2024

Abstract
Efflux transporters are a fundamental component of both prokaryotic and eukaryotic cells, play a crucial role in maintaining cellular homeostasis, and represent a key bridge between single cell and population levels. From a biomedical perspective, they play a crucial role in drug resistance (and especially multi-drug resistance, MDR) in a range of systems spanning bacteria and human cancer cells. Typically, multiple efflux transporters are present in these cells, and the efflux transporters transport a range of substrates (with partially overlapping substrates between transporters). Furthermore, in the context of drug resistance, the levels of transporters may be elevated either due to extra or intracellular factors (feedforward regulation) or due to the drug itself (feedback regulation). As a consequence, there is a real need for a transparent systems-level understanding of the collective functioning of a set of transporters and their response to one or more drugs. We develop a systems framework for this purpose and examine the functioning of sets of transporters, their interplay with one or more drugs and their regulation (both feedforward and feedback). Using computational and analytical work, we obtain transparent insights into the systems level functioning of a set of transporters arising from the interplay between the multiplicity of drugs and transporters, different drug–transporter interaction parameters, sequestration and feedback and feedforward regulation. These insights transparently arising from the most basic consideration of a multiplicity of transporters have broad relevance in natural biology, biomedical engineering and synthetic biology.
Insight, Innovation, Integration: Innovation: creating a structured systems framework for evaluating the impact of multiple transporters on drug efflux and drug resistance. Systematic analysis allows us to evaluate the effect of multiple transporters on one/more drugs, and dissect associated resistance mechanisms. Integration allows for elucidation of key cause-and-effect relationships and a transparent systems-level understanding of the collective functioning of transporters and their impact on resistance, revealing the interplay of key underlying factors. Systems-level insights include the essentially different behaviour of transporters as part of a group; unintuitive effects of influx; effects of elevated transporter-levels by feedforward and drug-induced mechanisms. Relevance: a systems understanding of efflux, their role in MDR, providing a framework/platform for use in designing treatment, and in synthetic biology design.
Quantifying microbial guilds
Authors: Rivas-Santisteban Juan , Yubero Pablo , Robaina-Estévez Semidán , González José M , Tamames Javier , Pedrós-Alió Carlos 
Published: March 2024

Abstract
The ecological role of microorganisms is of utmost importance due to their multiple interactions with the environment. However, assessing the contribution of individual taxonomic groups has proven difficult despite the availability of high throughput data, hindering our understanding of such complex systems. Here, we propose a quantitative definition of guild that is readily applicable to metagenomic data. Our framework focuses on the functional character of protein sequences, as well as their diversifying nature. First, we discriminate functional sequences from the whole sequence space corresponding to a gene annotation to then quantify their contribution to the guild composition across environments. In addition, we identify and distinguish functional implementations, which are sequence spaces that have different ways of carrying out the function. In contrast, we found that orthology delineation did not consistently align with ecologically (or functionally) distinct implementations of the function. We demonstrate the value of our approach with two case studies: the ammonia oxidation and polyamine uptake guilds from the Malaspina circumnavigation cruise, revealing novel ecological dynamics of the latter in marine ecosystems. Thus, the quantification of guilds helps us to assess the functional role of different taxonomic groups with profound implications on the study of microbial communities.
Predicting bacterial interaction outcomes from monoculture growth and supernatant assays
Authors: Schmitz Désirée A , Wechsler Tobias , Mignot Ingrid , Kümmerli Rolf 
Published: March 2024

Abstract
How to derive principles of community dynamics and stability is a central question in microbial ecology. Bottom-up experiments, in which a small number of bacterial species are mixed, have become popular to address it. However, experimental setups are typically limited because co-culture experiments are labor-intensive and species are difficult to distinguish. Here, we use a four-species bacterial community to show that information from monoculture growth and inhibitory effects induced by secreted compounds can be combined to predict the competitive rank order in the community. Specifically, integrative monoculture growth parameters allow building a preliminary competitive rank order, which is then adjusted using inhibitory effects from supernatant assays. While our procedure worked for two different media, we observed differences in species rank orders between media. We then parameterized computer simulations with our empirical data to show that higher order species interactions largely follow the dynamics predicted from pairwise interactions with one important exception. The impact of inhibitory compounds was reduced in higher order communities because their negative effects were spread across multiple target species. Altogether, we formulated three simple rules of how monoculture growth and supernatant assay data can be combined to establish a competitive species rank order in an experimental four-species community.
Implications for nitrogen and sulphur cycles: phylogeny and niche-range of Nitrospirota in terrestrial aquifers
Authors: Mosley Olivia E , Gios Emilie , Handley Kim M 
Published: March 2024

Abstract
Increasing evidence suggests Nitrospirota are important contributors to aquatic and subsurface nitrogen and sulphur cycles. We determined the phylogenetic and ecological niche associations of Nitrospirota colonizing terrestrial aquifers. Nitrospirota compositions were determined across 59 groundwater wells. Distributions were strongly influenced by oxygen availability in groundwater, marked by a trade-off between aerobic (Nitrospira, Leptospirillum) and anaerobic (Thermodesulfovibrionia, unclassified) lineages. Seven Nitrospirota metagenome-assembled genomes (MAGs), or populations, were recovered from a subset of wells, including three from the recently designated class 9FT-COMBO-42-15. Most were relatively more abundant and transcriptionally active in dysoxic groundwater. These MAGs were analysed with 743 other Nitrospirota genomes. Results illustrate the predominance of certain lineages in aquifers (e.g. non-nitrifying Nitrospiria, classes 9FT-COMBO-42-15 and UBA9217, and Thermodesulfovibrionales family UBA1546). These lineages are characterized by mechanisms for nitrate reduction and sulphur cycling, and, excluding Nitrospiria, the Wood–Ljungdahl pathway, consistent with carbon-limited, low-oxygen, and sulphur-rich aquifer conditions. Class 9FT-COMBO-42-15 is a sister clade of Nitrospiria and comprises two families spanning a transition in carbon fixation approaches: f_HDB-SIOIB13 encodes rTCA (like Nitrospiria) and f_9FT-COMBO-42-15 encodes Wood–Ljungdahl CO dehydrogenase (like Thermodesulfovibrionia and UBA9217). The 9FT-COMBO-42-15 family is further differentiated by its capacity for sulphur oxidation (via DsrABEFH and SoxXAYZB) and dissimilatory nitrate reduction to ammonium, and gene transcription indicated active coupling of nitrogen and sulphur cycles by f_9FT-COMBO-42-15 in dysoxic groundwater. Overall, results indicate that Nitrospirota are widely distributed in groundwater and that oxygen availability drives the spatial differentiation of lineages with ecologically distinct roles related to nitrogen and sulphur metabolism.
The impact of European Cohesion Policy: a spatial perspective
Authors: Amendolagine Vito , Prota Francesco , Serlenga Laura 
Published: March 2024

Abstract
Cohesion Policy is one of the core policy areas of the European Union and one of the largest expenditure items in its budget. Its impact is the subject of intense academic and policy debate, but its effectiveness is an empirical question still open. This article contributes to this debate by performing a region-specific investigation of the direct and indirect impact of Structural Funds expenditure. We employ a heterogeneous panel data model, which accommodates the spatial dependence in a heterogeneous setting and measures heterogeneous spatial spillover effects, both inward and outward. We also consider different channels of spatial spillovers with respect to standard geographical closeness. In particular, the introduction of new measures of proximity that explicitly consider economic linkages between regions is a novel contribution to the literature. The results clearly indicate that the impact of the Cohesion Policy, while positive overall, is highly heterogeneous and the Structural Funds expenditure generates substantial heterogeneous spatial spillovers: the positive effects do not remain confined to the target regions. Finally, strong spillover effects are channelled by value-added trade connections, particularly in regions belonging to the so-called ‘Central European Manufacturing Core’.
From Bauddha Deśa to Śākta Pīṭha: Re/Locating the Hindu Goddess Tārā
Authors: Bordeaux Joel 
Published: March 2024

Abstract
The incorporation of the goddess Tārā into the Hindu pantheon appears to have begun around the turn of the first millennium, a couple of centuries after her first mentions in Buddhist sources. The earliest Hindu texts concerned with Tārā tend to acknowledge this through a narrative wherein the Vedic sage Vasiṣṭha must travel to ‘Greater China’ to learn from the Buddha how to propitiate the goddess properly through the violation of brāhmaṇical purity codes for which Indian tantric traditions are infamous. Over time her ‘foreign’ associations faded, narratives linking Tārā to sites in Assam and Bengal became more prominent, and her worship drew closer to regional Hindu orthopraxy. This essay tracks the latter stages of that process especially through a reading of early modern ritual manuals in Sanskrit before considering a more recent revival of interest in the Hindu Tārā’s Buddhist connections as shown in Bengali sources and fieldwork.
Transitional dynamics in oncology clinical trials: evaluating the impact of Clinical Trials Act on cooperative groups
Authors: Nakamura Kenichi , Takeda Koji , Saito Akiko M , Kato Miho , Sato Shinya , Nakagawa Satoshi , Kawamoto Yasuyuki , Oki Eiji , Okamoto Isamu , Okamoto Hiroaki , Katayama Hiroshi , Mizusawa Junki , Kaba Harumi , Shibata Taro , Fukuda Haruhiko 
Published: March 2024

Abstract

Objective
large-scale multicentre clinical trials conducted by cooperative groups have generated a lot of evidence to establish better standard treatments. The Clinical Trials Act was enforced on 1 April 2018, in Japan, and it has remarkably increased the operational burden on investigators, but its long-term impact on cancer cooperative groups is unknown.

Methods
a survey was conducted across the nine major cooperative groups that constitute the Japan Cancer Trials Network to assess the impact of Clinical Trials Act on the number of newly initiated trials from fiscal year (from 1 April to 31 March) 2017 to 2022 and that of ongoing trials on 1 April in each year from 2018 to 2023.

Results
the number of newly initiated trials dropped from 38 trials in fiscal year 2017 to 26 trials in fiscal year 2018, surged to 50 trials in fiscal year 2019, but then gradually decreased to 25 trials by fiscal year 2022. Specified clinical trials decreased from 32 trials in fiscal year 2019 to 12 trials in fiscal year 2022. The number of ongoing trials was 220 trials in 2018, peaked at 245 trials in 2020, but then gradually decreased to 219 trials by 2023. The number of specified clinical trials has been in consistent decline. By April 2023, of the 20 ongoing non-specified clinical trials, nine adhered to Clinical Trials Act and 11 followed the Ethical Guidelines for Medical and Health Research Involving Human Subjects.

Conclusion
the number of multicentre clinical trials in oncology gradually decreased after the Clinical Trials Act’s enforcement, which underscores the need for comprehensive amendment of the Clinical Trials Act to streamline the operational process.
Sex and landscape influence spatial genetic variation in a large fossorial mammal, the Bare-nosed Wombat (Vombatus ursinus)
Authors: Tan Woei Jiun , Carver Scott , Martin Alynn M , Fountain-Jones Nicholas M , Proft Kirstin M , Burridge Christopher P 
Published: March 2024

Abstract
Dispersal is an important process that is widely studied across species, and it can be influenced by intrinsic and extrinsic factors. Intrinsic factors commonly assessed include the sex and age of individuals, while landscape features are frequently-tested extrinsic factors. Here, we investigated the effects of both sex and landscape composition and configuration on genetic distances among bare-nosed wombats (Vombatus ursinus)—one of the largest fossorial mammals in the world and subject to habitat fragmentation, threats from disease, and human persecution including culling as an agricultural pest. We analyzed a data set comprising 74 Tasmanian individuals (30 males and 44 females), genotyped for 9,064 single-nucleotide polymorphisms. We tested for sex-biased dispersal and the influence of landscape features on genetic distances including land use, water, vegetation, elevation, and topographic ruggedness. We detected significant female-biased dispersal, which may be related to females donating burrows to their offspring due to the energetic cost of excavation, given their large body sizes. Land use, waterbodies, and elevation appeared to be significant landscape predictors of genetic distance. Land use potentially reflects land clearing and persecution over the last 200 years. If our findings based on a limited sample size are valid, retention and restoration of nonanthropogenic landscapes in which wombats can move and burrow may be important for gene flow and maintenance of genetic diversity.
Financial-legal navigation reduces financial toxicity of pediatric, adolescent, and young adult cancers
Authors: Edward Jean , Northrip Kimberly D , Rayens Mary Kay , Welker Andrea , O’Farrell Rachel , Knuf Jennifer , Fariduddin Haafsah , Costich Julia , D’Orazio John 
Published: March 2024

Abstract

Background
Pediatric, adolescent, and young adult patients with cancer and their caregivers are at high risk of financial toxicity, and few evidence-based oncology financial and legal navigation programs exist to address it. We tested the feasibility, acceptability, and preliminary effectiveness of Financial and Insurance Navigation Assistance, a novel interdisciplinary financial and legal navigation intervention for pediatric, adolescent and young adult patients and their caregivers.

Methods
We used a single-arm feasibility and acceptability trial design in a pediatric hematology and oncology clinic and collected preintervention and postintervention surveys to assess changes in financial toxicity (3 domains: psychological response/Comprehensive Score for Financial Toxicity [COST], material conditions, and coping behaviors); health-related quality of life (Patient-Reported Outcomes Measurement Information System Physical and Mental Health, Anxiety, Depression, and Parent Proxy scales); and perceived feasibility, acceptability, and appropriateness.

Results
In total, 45 participants received financial navigation, 6 received legal navigation, and 10 received both. Among 15 adult patients, significant improvements in FACIT-COST (P = .041) and physical health (P = .036) were noted. Among 46 caregivers, significant improvements were noted for FACIT-COST (P &lt; .001), the total financial toxicity score (P = .001), and the parent proxy global health score (P = .0037). We were able to secure roughly $335 323 in financial benefits for 48 participants. The intervention was rated highly for feasibility, acceptability, and appropriateness.

Conclusions
Integrating financial and legal navigation through Financial and Insurance Navigation Assistance was feasible and acceptable and underscores the benefit of a multidisciplinary approach to addressing financial toxicity.

ClinicalTrials.gov registration
NCT05876325
Laparoscopic deroofing for a giant hepatic cyst with biliary communication: a case report
Authors: Ikeda Taro , Okazaki Taro , Manabe Yu , Nakanishi Rintaro , Kagiyama Hiroki , Owada Yoshiyuki , Hosono Masayoshi , Sendo Hiroyoshi 
Published: March 2024

Abstract
Previous reports describing laparoscopic deroofing as a management modality for a hepatic cyst with biliary communication remain limited. We present the case of a 76-year-old woman who was monitored for 4 years for a giant hepatic cyst in the right lobe of the liver. She presented to our department with a chief complaint of abdominal distension. Moreover, imaging revealed a 24-cm giant hepatic cyst. During laparoscopic deroofing, minimal bile leakage from the intra-cyst wall was observed, which was laparoscopically closed with sutures. No bile leakage or cyst recurrence was observed 18 months postoperative. This highlights that laparoscopic surgery may be used in managing hepatic cysts with biliary communication. Intraoperative findings may reveal biliary communication, which requires careful observation of the cyst wall after deroofing.