bluuebunny/crossref_metadata_2025_split huggingface dataset:
Artificial intelligence in surgery: evolution, trends, and future directions
Authors: Li Huiyang , Han Zhuoqi , Wu Haixiao , Musaev Elmar R. , Lin Yile , Li Shu , Makatsariya Alexander D. , Chekhonin Vladimir P. , Ma Wenjuan , Zhang Chao 
Published: December 2024

Artificial intelligence (AI) is significantly transforming surgery by enhancing precision, decision-making, and patient outcomes. This bibliometric analysis examines AI’s impact on surgery, highlighting research trends, key contributors, and evolving themes from 1998 to 2024. Utilizing data from the Web of Science Core Collection and analyzed through the Bibliometrix tool, the study reviews publication trends, author impact, institutional contributions, country-specific research activities, and keyword frequency. A total of 821 articles were examined, revealing a 14.53% annual growth rate in publications, increasing from one in 1998 to 328 in 2023. Influential contributors include 10 157 authors, notably HASHIMOTO DA and ITO M. Prominent institutions such as Harvard University and Stanford University, along with leading countries like the USA and China, play major roles in this field. High-frequency keywords identify core research areas: surgery, artificial intelligence, classification, diagnosis, and outcomes. Thematic evolution shows a shift from foundational concepts to advanced applications and interdisciplinary collaborations. AI integration into surgical practices is revolutionizing the field, driving advancements in precision, efficiency, and patient care. The study underscores significant research growth, influential contributors, and key trends, emphasizing the importance of continued interdisciplinary collaboration and innovation. Future research should focus on enhancing AI applications, addressing data quality and security challenges, and expanding into diverse surgical contexts to further improve surgical outcomes and patient care. AI in surgery is a rapidly evolving and promising field for innovation, with its full potential reliant on enhanced collaboration across disciplines.
The role of macrolides in severe community-acquired pneumonia and the potential impact of macrolide-resistant Mycoplamsa pneumoniae
Authors: Antonakos Nikos , Giamarellos-Bourboulis Evangelos J. , Niederman Michael S. 
Published: December 2024

Purpose of review
Define the utility of adjunctive macrolide therapy in patients with more severe forms of community-acquired pneumonia (CAP).

Recent findings
Guidelines recommend adjunctive macrolide therapy as an option for patients with CAP, admitted to the hospital. A large data set collected both retrospectively and prospectively, including several recent randomized controlled trials (RCTs) have shown that adjunctive macrolide therapy can reduce mortality and improve outcomes in patients with severe CAP, more effectively than other alternative therapies. This effect appears to be most evident in those with severe illness and appears to be independent of direct antimicrobial effects and may be a result of the immunomodulatory properties of macrolides. A recent RCT, the ACCESS study, showed a clinical benefit of macrolides in severe CAP patients, but this may have been the result of a reversal of infection-related immunoparalysis. Macrolides appear to be valuable for patients with more severe CAP, but their therapeutic value is being challenged by the recent emergence of macrolide-resistant Mycoplasma pneumoniae; however, the optimal therapy for this pathogen still needs to be defined.

Summary
New evidence has further advanced the role of macrolides as preferred adjunctive therapy for patients with severe CAP.
From Moral Injury Vulnerability to Protective Equity
Authors: Vimalathas Praveen , Gordon Elisa J. , Nieuwsma Jason A. , Meador Keith , Geevarghese Sunil K. 
Published: December 2024

Objective:
To examine the relationship between moral injury and surgical practice, further explore the concept of protective equity, and understand its role in mitigating the impact of morally injurious events throughout a surgical career.

Background:
Moral injury in healthcare settings has evolved from Jonathan Shay’s original definition, modified by Brett Litz and others, to encompass the psychological impact of adverse patient outcomes on medical practitioners. Early career surgeons may be particularly susceptible to moral injury, yet the factors influencing this vulnerability remain poorly understood.

Methods:
An analysis of existing literature on moral injury in healthcare, combined with an examination of surgical career trajectories and outcome reporting was conducted. The concepts of protective equity and vulnerability are introduced, defined, and theoretically extrapolated across a surgical career.

Results:
Evidence suggests that surgical complications significantly contribute to moral injury, particularly among early career surgeons. We propose a model wherein protective equity accumulates over a surgical career, whereas vulnerability follows an M-shaped curve with peaks in early and late career.

Conclusions:
Early career surgeons face a precarious imbalance of low protective equity and high vulnerability, especially immediately post-training. Strategies to address this dynamic include providing: specific education when onboarding faculty, and longitudinal peer support by senior, trained surgeons.
Neoadjuvant Pembrolizumab in Stage I-III Deficient Mismatch Repair Colon Cancer
Authors: Gögenur Ismail , Justesen Tobias Freyberg , Tarpgaard Line Schmidt , Bulut Mustafa , Hansen Torben Frøstrup , Jensen Lars Henrik , Rahr Hans Bjarke , Kirkegaard Tove , Balsevicius Lukas , Raskov Hans , Petersen Peter Clausager , Eriksen Jens Ravn , Salomon Søren , Fiehn Anne-Marie Kanstrup , Brandsborg Søren , Gotschalck Kåre Andersson , Emmertsen Katrine J. , Born Pernille Wolder , Thorlacius-Ussing Ole , Lauritzen Michael Bødker , Olesen René Krøjgaard , Poulsen Laurids Østergaard , Lykke Jakob , Schou Jakob , Buskov Laura , Krarup Peter-Martin , Andersen Claus Lindbjerg , Pfeiffer Per , Qvortrup Camilla 
Published: December 2024

Objective:
This clinical trial investigated the safety and efficacy of single-cycle pembrolizumab in patients with localized deficient mismatch repair (dMMR) colon cancer.

Background:
Neoadjuvant immunotherapy has induced remarkable rates of pathological complete response in patients with dMMR colon cancer. However, the optimal length and type of treatment are yet to be determined.

Methods:
This was an investigator-initiated, multicenter, single-arm, phase II study (ClinicalTrials.gov: NCT05662527) investigating the safety and efficacy of neoadjuvant pembrolizumab in patients with stage I-III dMMR colon cancer. Patients received a single cycle of pembrolizumab 4 mg/kg (maximum 400 mg) and underwent surgery three to five weeks later. An interim safety and efficacy analysis after including 42 patients was pre-planned. The primary outcomes were safety and efficacy (pathological complete response in more than 20% of patients).

Results:
Between February 2023 and September 2023, 42 patients were enrolled at five Danish hospitals. All patients received pembrolizumab and underwent surgery, except one patient who refused to undergo surgery. Surgery was performed a median of 32 days after pembrolizumab treatment. Twenty surgical complications were observed in 16 of 41 patients (39%), three of which were above Clavien-Dindo grade 2. Two were grade 3b, and one was a surgery-related grade 5 gastric ulcer perforation. Three adverse events were grade 3. No grade 4 or 5 adverse events were reported. Of the evaluable patients, 46% (19/41) achieved a pathological complete response, while 61% had a major pathological response.

Conclusion:
In conclusion, neoadjuvant single-cycle pembrolizumab was well tolerated and effective in patients with localized dMMR colon cancer. Thus, the inclusion of patients was continued until 85 patients.
ΔNP63 defines an exocrine-committed multipotent progenitor subset in the murine pancreas
Authors: Coolens Katarina , Van der Vliet Melissa , Van Campenhout Jente , del Pozo Natalia , Torres-Cano Alejo , Olson Catharina , Xu Jianming , Lickert Heiko , Rovira Meritxell , Houbracken Isabelle , Baldan Jonathan , Real Francisco X. , Spagnoli Francesca M. , Rooman Ilse 
Published: December 2024

AbstractCellular plasticity underpins heterogeneity in embryogenic progenitor cells and cancer cells. The transcription factordeltaNp63(ΔNp63) has been implicated in regulating cellular plasticity in several epithelial tissues. Despite a recently established role in steering plasticity of pancreatic cancer, ΔNp63 remains unstudied in pancreatic development.Using murine single-cell sequencing data and RNA and proteinin situstainings, we assessed the spatio-temporal expression ofTrp63and ΔNP63 in the embryonic pancreas. ΔNP63 demonstrates a transient and spatially restricted expression in the multipotent pancreatic progenitor (MPP) compartment delineating pro-exocrine progenitor cells. Lineage tracing of TP63+cells marks a subset of MPPs and descendant exocrine acinar and centro-acinar/terminal duct cells. Lack of ΔNP63 in knock-out mice leads to hypotrophic exocrine acini with reduced levels of differentiation markers.In summary, ΔNp63 confers heterogeneity within the MPP compartment, supporting exocrine cell development. These new insights in developmental plasticity have potential implications for pancreatic regeneration and cancer.
Engineering kidney developmental trajectory using culture boundary conditions
Authors: Huang Aria Zheyuan , Prahl Louis S. , Xu Karen , Mauck Robert L. , Hughes Alex J. 
Published: December 2024

AbstractKidney explant cultures are traditionally carried out at air-liquid interfaces, which disrupts 3D tissue structure and limits interpretation of developmental data. To overcome this limitation, we developed a 3D culture technique using hydrogel embedding to capture morphogenesis in real time. We show that 3D culture better approximatesin vivo-like niche spacing and dynamic tubule tip rearrangement, as well asin vivo-like presentation of branching defects under perturbations to glial cell-derived neurotrophic factor (GDNF)-REarranged duringTransfection (RET) tyrosine kinase signaling. We find that the concentration of the embedding matrix influences the number of nephrons per ureteric bud (UB) tip and the spacing between tips. To isolate the effect of specific material properties on explant development, we introduce engineered acrylated hyaluronic acid hydrogels that allow independent tuning of stiffness and adhesion. We find that sufficient stiffness and adhesion are both required to maintain kidney shape. Matrix stiffness has a “Goldilocks effect” on the nephron per UB tip balance centered at ∼2 kPa, while higher matrix adhesion increases nephron per UB tip ratio. Our technique captures large-scale,in vivo-like tissue morphogenesis in 3D, providing a platform suited to contrasting normal and congenital disease contexts. Moreover, understanding the impact of boundary condition mechanics on kidney development benefits fundamental renal research and advances the engineering of next-generation kidney replacement tissues.
NK cells control the progression of myelodysplastic syndrome but become initial disease target inNUP98-HOXD13mouse model
Authors: Telliam-Dushime Gladys , Ciesla Maciej , Lilljebjörn Henrik , Ungerbäck Jonas , Yuan Ouyang , Vo Dang Nghiem , Kotova Olga , Fioretos Thoas , Bryder David , Bellodi Cristian , Sitnicka Ewa 
Published: December 2024

ABSTRACTStudies inNUP98/HOXD13mouse model (NHD13tg), progressing from myelodysplastic syndrome (MDS) to different forms of leukemia, demonstrated that T cells had a limited anti-leukemia effect, suggesting the involvement of other immune cells. Natural killer (NK) cells control viral infection and cancer. In MDS and acute myeloid leukemia (AML), patients often acquire disease-induced NK cell dysfunctions. Here, we report that NK cells from NHD13tgmice were reduced before the MDS-onset and specific NK cell depletion accelerated the disease progression and severity. NK cells from NHD13tgmice showed perturbed differentiation and impaired IL-15/IL-2 responses. These defects were cell-intrinsic and mainly affected the KLRG1+mature NK cells. The expression of Nfil3, Klf2 and Id2 genes, crucial for NK cell development, homeostasis and IL-15 responsiveness, was altered in immature NK cells from NHD13tgmice. Interestingly, these genes were changed in MDS and AML bone marrow patient-samples compared to healthy donors. Our findings highlight a critical role for NK cells in controlling MDS progression and identify new genetic markers for MDS and AML.
Variation in Head and Pinna Morphology of PreservedPeromyscus Spp. Specimens and Implications for Auditory Function
Authors: Sergott Casey E. , Rodman Katelynn , Greene Nathaniel T. , Li Ben-Zheng , Alarcon Genesis A. , Machado Fabio A. , McCullagh Elizabeth A. 
Published: December 2024

AbstractThe characteristics of an animal’s head and pinna mark the beginning of auditory communication. Auditory communication is broadly achieved by receiving sounds from the environment and plays a vital role in an animal’s ability to perceive and localize sounds. Natural history museums and collections along with their vast repositories of specimens provide a unique resource for examining how the variability in both the size and shape of the head and pinna cause variability in the detection of acoustic signals across species. Using this approach, we measured the dimensions of the head and pinna of over 1,200 preserved specimens ofPeromyscus boylii,P. californicus,P. gossypinus,P. leucopus,P. maniculatus, andP. truei, followed by a series of head-related transfer functions (HRTFs) on several individuals to study the relationship between morphology and available auditory information. Our morphological results show significant variation in pinna length and width, as well as in the distance between the two ears across the six species. ITDs and ILDs were calculated and demonstrated consistent results across species, suggesting the differences in head and pinna size do not significantly modify these cues. Not only does this study contribute to existing research on external morphology and auditory function, but it also provides valuable insight into the use of preserved specimens in auditory research, an area that is currently understudied.Summary statementThis work aims to provide insight into using natural history museum specimens for morphological research pertaining to the auditory system in small mammals.
Multiplexed mosaic tumor models reveal natural phenotypic variations in drug response within and between populations
Authors: Yu Johnny X. , Suh Jung Min , Popova Katerina D. , Garcia Kristle , Joshi Tanvi , Culbertson Bruce , Spinelli Jessica B. , Subramanyam Vishvak , Lou Kevin , Shokat Kevan M. , Weissman Jonathan , Goodarzi Hani 
Published: December 2024

AbstractMany agents that show promise in preclinical cancer models lack efficacy in patients due to patient heterogeneity that is not captured in traditional assays. To address this problem, we have developed GENEVA, a platform that measures the molecular and phenotypic consequences of drug perturbations within diverse populations of cancer cells at single-cell resolution, bothin vitroandin vivo. Here, we apply GENEVA to study the KRAS G12C inhibitors, recapitulating known properties of these drugs and uncovering a previously unknown role for mitochondrial activation in cell death induced by KRAS inhibition. We demonstrate that this finding can be leveraged for the development of combination therapies with greater efficacy. Finally, we show that the application of GENEVA within vivomouse models revealed epithelial to mesenchymal transition (EMT) as a key mechanism for resistance to KRAS G12C inhibition.
The major histocompatibility complex: a double-edged sword in fungal disease susceptibility
Authors: Fu Minjie , Eimes John A 
Published: December 2024

AbstractChytridiomycosis, caused byBatrachochytrium dendrobatidis(Bd), threatens amphibian populations worldwide. MHC II has been implicated in Bd susceptibility, but the role of MHC in Bd susceptibility remains poorly understood. In this study, we clustered MHC II ß1 alleles into functional supertypes and investigated their diversity in amphibian species with differential susceptibility. Despite sharing similar alpha diversity in MHC II supertypes, the hosts exhibited distinct beta diversity. We demonstrated MHC supertypes, rather than individual MHC alleles, predict Bd susceptibility, with some supertypes conferring protection and others increasing risk. This suggests that MHC alleles function more as part of a complex network than as independent entities. We also quantified MHC allelic-specific expression and observed individual-level variability in expression across both species. Notably, positive and negative associations among MHC alleles were observed. The similarity of these patterns between the two species suggests the presence of conserved regulatory mechanisms across amphibians. Our results provide valuable resources and insights to advance the understanding of adaptive immunological systems and to develop targeted conservation strategies to preserve biodiversity.
Targeting Innate Immune Signaling in Glioma-Initiating Cells Impairs Self-Renewal and Radiation-Induced Cellular Plasticity
Authors: Cardenas Anjelica M. , Azizi Linda , Ioannidis Angeliki , Bhat Kruttika , He Ling , Mohammadi Mahya , Pajonk Frank 
Published: December 2024

AbstractOrganisms constantly face environmental stressors that threaten their cellular and genomic integrity. In their response, pathogen-associated molecular patterns (PAMPs) and/or damage-associated molecular patterns (DAMPs) are detected by pattern recognition receptors (PRRs) and trigger the innate immune response. In this study we tested the hypothesis that DAMPs contribute to radiation-induced cellular plasticity in Glioblastoma (GBM). GBM is known to be organized hierarchically with a small number of glioma-initiating cells (GICs) driving treatment resistance and recurrences.Using patient-derived GBM specimens, we employed sphere forming capacity assays andin vitroextreme limiting dilution assays to examine how innate immune receptor signaling impacts the maintenance and self-renewal of GICs. By leveraging an imaging system for putative GICs we determinedde novoinduction of GICs from non-stem glioma cells.We find that GIC maintenance after irradiation is mediated by cGAS-independent STING signaling, possibly involving signaling through TLR4 and TLR9. Induction of radiation-induced plasticity involves TLR3 signaling, with potential roles for other receptors and processes modulated by MyD88. These findings suggest that targeting innate immune signaling could prevent radiation-induced cellular plasticity for potential therapeutic benefit.
Prediction of Stature using Percutaneous long bones of the Upper and Lower limbs among Asante and Ewe Ethnic Groups in Ghana
Authors: Okwan Daniel Kobina , Abaidoo Chrissie Stansie , Wepeba Pet-Paul , Robertson Juliet , Bempah Samuel Kwadwo Peprah , Obeng Priscilla , Domfeh Ethel Akua Achiaa , Afriyie Sarah Owusu , Asante Thomas Kwaku 
Published: December 2024

AbstractIntroductionSophisticated technological advancements for identification of people are readily available in developed countries. Meanwhile, relatively less expensive algorithms in physical anthropometry could be employed for such identification purposes. Although such evaluations have been done in some countries, due to interpopulation variations, such relations should be ethnic-and sex-specific.AimTherefore, the present study sought to assess the relationship between long bones of upper and lower limbs among two ethnic groups in Ghana for stature estimation.MethodologyUsing a purposive non-random sampling technique, participants made up of 140 Asantes and 102 Ewes aged 20 to 25 years were recruited after an ethical approval was obtained from the Committee on Human Research, Publication and Ethics, KNUST.ResultsFor the same sex, there was no statistically significant difference between Asantes and Ewes with respect to height. The most useful parameter for stature estimation among the Asante males was left fibular and tibial lengths with that of the females being left ulnar, fibular and radial lengths. However, for the Ewe males, the most significant parameters for height estimation were right fibular and humeral lengths with the Ewe females being right tibial and humeral lengths.ConclusionFindings of the study are useful for the identification of humans with dismembered body parts involved in various disasters such as automobile accidents. The database and formulae derived would be useful for stature estimation needed in biological profiling and other assessments of bedridden patients.
Applying deconstructed sourdough communities and fermentation parameters to low-FODMAP wheat bread production
Authors: Wittwer Anna Elizabeth , Li Jiaying Amanda , Howell Kate 
Published: December 2024

AbstractAimsDespite being made with the same starting materials, standard and sourdough bread differ in terms of levels of fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs). This study aims to assess the impact of a selected yeast-bacteria co-culture isolated from sourdough starters in conjunction with varying bread-making process parameters on bread FODMAP content and overall quality.Methods and ResultsAn investigation of the microbial composition of sourdough starters found that many containMaudiozyma humilisandFructilactobacillus sanfranciscensis. A selected pairing was used for small-scale bread-making, and dough fermentation and bread quality parameters were assessed. The sourdough microbes exerted distinctive effects on dough gassing capacity and FODMAP composition in comparison to baker’s yeast. To meet low-FODMAP cutoff values, the presence of a fermenting yeast and an extended dough fermentation time (> 6 h) were necessary. Sensory panellists displayed similar levels of preference for bread fermented by baker’s yeast and the sourdough co-culture and tended to prefer and detect more complex aromas in co-culture bread fermented for 24 h than for 6 h.ConclusionsAn extended, low-temperature dough fermentation regimen can be used with a co-culture of common sourdough fermentation microbes to produce low-FODMAP, well-liked bread with standard bread-making materials.