bluuebunny/crossref_metadata_2025 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.
Material economic hardships are﻿ associated with adverse 1-year outcomes after pediatric liver transplantation: Prospective cohort results from the multicenter SOCIAL-Tx Study
Authors: Wadhwani Sharad I. , Squires James E. , Hsu Evelyn , Gupta Nitika , Campbell Kathleen , Zielsdorf Shannon , Vittorio Jennifer , Desai Dev M. , Ebel Noelle H. , Shui Amy M. , Bucuvalas John C. , Gottlieb Laura M. , Lyles Courtney R. , Lai Jennifer C. ,   on behalf of the Society of Pediatric Liver Transplantation
Published: December 2024

Pediatric liver transplant outcomes exhibit disparities, necessitating the identification of modifiable risk factors to develop targeted interventions. We characterized associations between household material economic hardship (eg, financial barriers to housing or food) and pediatric liver transplant outcomes. We recruited pediatric recipients of liver transplants <18 years at the time of transplant across 8 US centers. Our primary exposure was ≥1 household material economic hardship (ie, food insecurity, housing instability, transportation challenges, or utility concerns), measured using the Accountable Healthcare Communities screening tool. Outcomes included 90-day and 1-year (1) total inpatient bed-days, and (2) episodes of T-cell–mediated rejection. Of the 77 participants (36% female), 34% reported household material economic hardship. Such hardship was associated with increased total inpatient bed-days within 90 days (ratio estimate: 1.45, 95% CI: 1.08, 1.96); the association persisted after adjusting for health literacy, insurance, and transplant center (ratio estimate: 1.37, 95% CI: 1.02, 1.84). Household material economic hardship was associated with total inpatient bed-days within 1 year after transplant (ratio estimate: 3.2, 95% CI: 1.1, 10.1); associations diminished in multivariable analyses (ratio estimate: 2.2, 95% CI: 0.7, 6.9). Household material economic hardship was associated with increased risk of T-cell–mediated rejection within 1 year of transplant (relative risk: 2.1, 95% CI: 1.1, 4.2); the association diminished in propensity-score matched analyses (relative risk: 1.4, 95% CI: 0.9, 2.3). Our findings highlight the adverse influence of household material economic hardship on pediatric liver transplant outcomes within the first year. Targeted social risk assistance and adjustment strategies offer actionable avenues to mitigate these challenges and enhance outcomes in pediatric recipients of liver transplants.
Principles and biomechanical response of normal gait cycle to measure gait parameters for the alignment of prosthetics limb: A technical report
Authors: Kumar Santosh , Bhowmik Sumit
Published: December 2024

The limb amputations caused due to emergent incidents of trauma injuries and vascular diseases currently represent crucial global problems. The patients/amputees with limb amputation who lost the residual limb (knee-ankle foot system) must depend on the prosthetic limb. Prosthetic clinicians and technicians have attempted to develop optimal limb prosthetics that will enhance the ability and functional elements of the patients/users. However, the amputees still do not gain the same level of comfort and functional stability as compared to normal limbs (without amputation). Thus, to provide that comfort and stability, proper construction with accurate positioning and alignment of constructed prosthetic limb is crucial to reconstitute these amputees/patients to do their activities for daily life. The objective of technical report is to provide the brief summary about basic principle and biomechanics regarding gait analysis, construction, and alignment of prosthetic limb during gait cycle. The study also summarized the kinematics and kinetic biomechanical response of prosthetic limbs to assess the biomechanics of limb prosthetics, socket assembly principle, gait parameters, and static and dynamic alignment during walking. The basic principle of positioning and alignment with different flexion and torque moment at hip, knee, and ankle joint has been analyzed.
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.

New evidence has further advanced the role of macrolides as preferred adjunctive therapy for patients with severe CAP.
Comparison of the Cone Beam Computed Tomography-Based Analysis of the Masseter Muscle Between Epilepsy Patients and Healthy Subjects
Authors: Polat Sema , Yüksel Hazal Duyan , Evlice Burcu , Bölgen Çağatay , Kaya Ömer , Aksay Ufuk Can , Öksüzler Fatma Yasemin , Öksüzler Mahmut , Tunç Mahmut , Özşahin Esin , Göker Pinar
Published: December 2024

It is important to investigate the changes in the masseter muscle, one of the chewing muscles, in epilepsy patients and to determine whether epilepsy can be effectively predicted on muscle. The aim of this study is to measure masseter muscle thickness, circumference and cross-sectional area in individuals with epilepsy and healthy individuals. This study was performed with 128 individuals (64 epilepsy patients and 64 healthy subjects) aged between 18 to 59 years. The mean cross-sectional area, thickness and circumference determined by measuring both of the masseter muscles were using cone beam computed tomography. The mean right masseter muscle cross-sectional area varied across age groups in epilepsy individuals (P=0.020). Significant differences were observed in the right masseter muscle circumference among age groups in epilepsy individuals (P=0.003). Significant differences were observed in the mean among age groups in epilepsy individuals (P=0.004). Statistically significant differences were observed in the mean right masseter muscle cross-sectional area between sexes in healthy individuals (P<0.001). Similarly, significant differences were observed in the mean right masseter muscle thickness between sexes in healthy individuals (P<0.001). Significant differences were observed in the mean left masseter muscle cross-sectional area between sexes in healthy individuals (P<0.001). Although jaw joint’s muscular dislocations are common, the masseter muscle, which has a very strong function in masticatory movements, is very important in terms of location, neighbourhood and clinical aspects. For this reason, our study examining the masseter muscle morphometric measurements in the epileptic and healthy population using cone beam computed tomography provides important information and normative data.
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.
Morphogenesis of pteraspid heterostracan oral plates and the evolutionary origin of teeth
Authors: Grohganz Madleen , Johanson Zerina , Keating Joseph N. , Donoghue Philip C. J.
Published: December 2024

Teeth are a key vertebrate innovation; their evolution is generally associated with the origin of jawed vertebrates. However, tooth-like structures already occur in jawless stem-gnathostomes; heterostracans bear denticles and morphologically distinct tubercles on their oral plates. We analysed the histology of the heterostracan denticles and plates to elucidate their morphogenesis and test their homology to the gnathostome oral skeleton. We identified a general model of growth for heterostracan oral plates that exhibit proximal episodic addition of tubercle rows. The distal hook exhibits truncated lamellae compatible with resorption, but we observe growth layers to be continuous between denticles. The denticles show no evidence of patterns of apposition or replacement indicating tooth homology. The oral plates and dermal skeleton share the same histological layers. The denticles grew in a manner comparable to the oral plate tubercles and the rest of the dermal skeleton. Our test of phylogenetic congruence reveals that the distribution of internal odontodes is discontinuous, indicating that the capacity to form internal odontodes evolved independently several times among stem-gnathostomes. Our results support the ‘outside-in’ hypothesis and the origin of teeth through the spread of odontogenic competence from extra-oral to oral epithelia and the subsequent co-option to a tooth function in gnathostomes.
Desert ants avoid ambush predator pits depending on position, visual landmarks and trapped nestmates
Authors: Bar Adi , Raveh-Pal Eden , Subach Aziz , Foitzik Susanne , Scharf Inon
Published: December 2024

Central-place foragers face high predation risk when repeatedly using routes near their nest, as predators can learn to ambush them there. We investigated the factors influencing the likelihood of desert ant foragers falling into pitfall traps, simulating common predators such as antlions or spiders. We varied the spatial configuration of the pitfall traps, the presence of trapped nestmates and the availability of visual landmarks to study the workers’ susceptibility to falling into pits and their foraging success. Our results showed that a zigzag configuration of pits led to the fewest workers reaching the food reward, compared with straight-line and right-angled-triangle configurations. Over successive runs, workers became more efficient, with fewer falls into pits and faster food discovery, suggesting they either learned the locations of the pits or became more cautious. In any case, the ants learned about important landscape features close to their nest and the best way of navigating around it. Additionally, we examined the impact of trapped nestmates and visual landmarks. We found that pits marked with visual landmarks resulted in fewer falls. However, pits containing trapped nestmates attracted more ants, impaired food discovery and increased falling rates into pits, thereby imposing a twofold cost on ant foragers.
Multispecies genetic structure scales with β-diversity across river hierarchies in a freshwater mussel biodiversity hotspot
Authors: Bucholz Jamie R. , Hopper Garrett W. , Sánchez González Irene , Jackson Colin R. , Garrick Ryan C. , Atkinson Carla L. , Lozier Jeffrey D.
Published: December 2024

Ecological theory predicts that species turnover among communities (e.g. β-diversity) and genetic turnover among populations within species (e.g.
F
ST
) should be positively correlated if similar processes influence colonization and occupancy of species and gene flow and genetic drift of populations within a metacommunity. Using recently published population genomic data from multiple populations of 15 freshwater mussel (Unionidae) species across seven rivers in the Mobile and Tennessee River basins of the south-eastern USA, we conducted novel analyses examining the relationship between taxonomic turnover (β-diversity) among communities and genetic differentiation (
F
ST
) within these species.
F
ST
and β-diversity were both hierarchically structured, and strong basin effects and isolation-by-distance were observed for β-diversity and for
F
ST
among populations within most species. Furthermore, β-diversity and
F
ST
were directly correlated for the overall community and among sites for individual species, indicating that factors shaping turnover among mussel assemblages are similar at the species and genetic levels. The widespread associations between turnover metrics at the community and population genetic levels of biological organization suggest that parallel processes govern species composition and intraspecific connectivity in freshwater mussel metacommunities.
The potential of remote sensing for improved infectious disease ecology research and practice
Authors: Teitelbaum Claire S. , Ferraz António , De La Cruz Susan E. W. , Gilmour Morgan E. , Brosnan Ian G.
Published: December 2024

Outbreaks of COVID-19 in humans, Dutch elm disease in forests, and highly pathogenic avian influenza in wild birds and poultry highlight the disruptive impacts of infectious diseases on public health, ecosystems and economies. Infectious disease dynamics often depend on environmental conditions that drive occurrence, transmission and outbreaks. Remote sensing can contribute to infectious disease research and management by providing standardized environmental data across broad spatial and temporal extents, often at no cost to the user. Here, we (i) conduct a review of primary literature to quantify current uses of remote sensing in disease ecology; and (ii) synthesize qualitative information to identify opportunities for further integration of remote sensing into disease ecology. We identify that modern advances in airborne remote sensing are enabling early detection of forest pathogens and that satellite data are most commonly used to study geographically widespread human diseases. Opportunities remain for increased use of data products that characterize vegetation, surface water and soil; provide data at high spatio-temporal and spectral resolutions; and quantify uncertainty in measurements. Additionally, combining remote sensing with animal telemetry can support decision-making for disease management by providing insights into wildlife disease dynamics. Integrating these opportunities will advance both research and management of infectious diseases.
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

Cellular 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

Kidney 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

Studies 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

The 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 statement

This 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

Many 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

Chytridiomycosis, 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

Organisms 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

Introduction

Sophisticated 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.

Aim

Therefore, 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.

Methodology

Using 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.

Results

For 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.

Conclusion

Findings 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

Aims

Despite 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 Results

An 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.

Conclusions

An 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.
Clathrins are involved in the endocytosis of host cytosol in the malaria parasite
Authors: Miao Jun , Ning Gang , Xia Xian , Liang Xiaoying , Lucky Amuza Byaruhanga , Siddiqui Faiza , Min Hui , Wang Chengqi , Li Xiaolian , Zhou Z. Hong , Cui Liwang
Published: December 2024

In eukaryotic cells, clathrins interact with adaptor protein complexes to regulate key intracellular trafficking events. Specifically, they are associated with the adaptor protein (AP) complex-2 (AP2) to facilitate endocytosis and AP1 to mediate secretion and trafficking between endosome and Golgi. InPlasmodium falciparum,recent studies revealed that the Kelch domain-containing protein 13 and AP2 participate in hemoglobin uptake via cytostomes. However, clathrins appear not to be involved in this process because they primarily associate with AP1. To investigate the roles of clathrins inP. falciparum, we characterized the clathrin heavy chain (PfCHC), the clathrin light chain (PfCLC), and the AP1 γ subunit (PfAP1 γ). Extensive interactome analyses confirmed the major association of clathrins with AP1 components alongside proteins involved in cytostome formation. Live-cell imaging and protein colocalization studies showed thatPfCHC,PfCLC, andPfAP1 γ are localized in the parasite cytoplasm, predominantly at the parasite periphery and near the cis-Golgi. Ultrastructural studies using ascorbate peroxidase 2- based electron microscopy confirmed their presence at coated vesicle-like structures at the parasite periphery and, unexpectedly, at the collars of cytostomes. Consistent with these observations, the knockdown ofPfCHC led to the formation of abnormally long cytostome tubes and impaired hemoglobin digestion. This study demonstrates that clathrins are essential for proper cytostome formation inP. falciparum, highlighting their critical role in the parasite’s hemoglobin uptake and digestion processes.

IMPORTANCE

Malaria is still one of the most severe public health problems worldwide and understanding how malaria parasites obtain hemoglobin from their host cells, red blood cells (RBCs), is critical for identifying targets for antimalarials. In this study, affinity purification revealed that clathrins (PfCHC andPfCLC) were not only mainly associated with AP1 complex but also marginally interacted with proteins that participated in hemoglobin uptake. Localization analysis demonstrated that clathrins and AP1 coated the clusters of vesicles at the parasite periphery and at the neck of the cytostome, an organelle for hemoglobin uptake. Consistently, the knockdown ofPfCHC caused the formation of abnormally long cytostome tubes and reduced hemoglobin digestion. Collectively, this study demonstrates that clathrins play a critical role in the parasite’s hemoglobin uptake.
Pyruvate Kinase Directly Generates GTP in Glycolysis, Supporting Growth and Contributing to Guanosine Toxicity
Authors: She Fukang , Liu Kuanqing , Anderson Brent W , Pisithkul Tippapha , Li Yanxiu , Fung Danny K. , McCue Tyler , Mulhern William , Amador-Noguez Daniel , Wang Jue D.
Published: December 2024

Guanosine triphosphate (GTP) is essential for macromolecular biosynthesis, and its intracellular levels are tightly regulated in bacteria. Loss of the alarmone (p)ppGpp disrupts GTP regulation inBacillus subtilis, causing cell death in the presence of exogenous guanosine and underscoring the critical importance of GTP homeostasis. To investigate the basis of guanosine toxicity, we performed a genetic selection for spontaneous mutations that suppress this effect, uncovering an unexpected link between GTP synthesis and glycolysis. In particular, we identified suppressor mutations inpyk, which encodes pyruvate kinase, a glycolytic enzyme. Metabolomic analysis revealed that inactivating pyruvate kinase prevents guanosine toxicity by reducing GTP levels. Although traditionally associated with ATP generation via substrate-level phosphorylation,B. subtilispyruvate kinasein vitrowas found to produce GTP and UTP approximately ten and three times more efficiently than ATP, respectively. This efficient GTP/UTP synthesis extends toEnterococcus faecalisandListeria monocytogenes, challenging the conventional understanding of pyruvate kinase’s primary role in ATP production. These findings support a model in which glycolysis directly contributes to GTP synthesis, fueling energy-demanding processes such as protein translation. Finally, we observed a synergistic essentiality of the ΔndkΔpykdouble mutant specifically on glucose, indicating that pyruvate kinase and nucleoside diphosphate kinase are the major contributors of NTP production and complement each other during glycolysis. Our work highlights the critical role of nucleotide selectivity in pyruvate kinase and its broader implications in cellular physiology

Importance

In this study, we reveal pyruvate kinase, a key glycolytic enzyme, primarily generates GTP from GDP inBacillus subtilis, relatively to other trinucleotides such as ATP. This finding, uncovered through genetic selection for mutants that suppress toxic GTP overaccumulation, challenges the conventional understanding that pyruvate kinase predominantly produces ATP via substrate-level phosphorylation. The substantial role of GTP production by pyruvate kinase suggests a model where glycolysis rapidly and directly supplies GTP as the energy currency to power high GTP-demanding processes such as protein synthesis. Our results underscore the importance of nucleotide selectivity (ATP vs. GTP vs UTP) in shaping the physiological state and fate of the cell, prompting further exploration into the mechanisms and broader implications of this selective nucleotide synthesis.
Monopole-fermion scattering in a chiral gauge theory
Authors: Bolognesi Stefano , Bucciotti Bruno , Luzio Andrea
Published: December 2024

The scattering of electrically charged fermions on magnetic monopole leads to the Callan-Rubakov effect. We discuss some aspects of this problem for Abelian gauge theories with chiral fermions in a Dirac monopole background. In some cases, it is possible to embed the theory in a non-Abelian gauge theory where the monopole is regularized as a ’t Hooft-Polyakov monopole. One theory of this kind is the SU(N) chiral gauge theory with fermions in the representation □□⊕     ¯ ⊕ 8 × □¯, also called the “ψχη” model, with an extra adjoint scalar that induces the abelianization of the gauge group. We examine this model in detail and provide a possible solution for the condensates around the monopole, the symmetry preserving boundary conditions, and discuss the particle scattering problem.

Published by the American Physical Society
2024
Metamodeling of turbofan engine compressor characteristics using SVM-based improved Kriging method
Authors: Guo Chaochao , Sun Youchao , Yu Rourou , Peng Chong
Published: December 2024

Purpose

The purpose of this paper is to overcome the inherent lack of precision in commonly used interpolation procedures when solving the mathematical model of turbofan engines, as well as to address the issue that the theoretical variogram model in traditional Kriging models is prone to subjective selection bias, which makes it impossible to accurately capture the inherent fluctuation patterns in compressor data.

Design/methodology/approach

To mitigate this challenge, based on the spatial distribution characteristics of the compressor characteristic data of a certain type of turbofan engine, the input and output dimensions of the model are defined. By determining the stable operating region from the original component data, the authors use the proposed Kriging method improved with a support vector machine model to reconstruct the characteristics at unknown speeds within this region. The effectiveness of the proposed method is evaluated using the established assessment metrics.

Findings

Experimental results demonstrate that the proposed method exhibits significant advantages over the conventional Kriging approach. Specifically, it leads to a substantial reduction in root mean square error and mean absolute error by 0.0153/0.0118 (low speed), 0.1306/0.0362 (medium speed) and −0.0066/0.2366 (high speed).

Originality/value

This refined approach not only offers notable engineering applicability but also contributes significantly to the enhancement of aerospace engine model solutions’ precision.
How to find the optimal time for contractor involvement in infrastructure projects?
Authors: Memić Nadina , Tadayon Allen , Ishtiaque Tausif Ahmed , Klakegg Ole Jonny , Wondimu Paulos Abebe , Lædre Ola
Published: December 2024

Purpose

There is a general assumption that the early involvement of the contractor contributes to value in construction projects. While early contractor involvement (ECI) may improve the value, some studies identify challenges with ECI. This paper aims to identify the main parameters that can be used to determine the optimal time for contractor involvement and examine how these parameters can be used by clients to develop a systematic method for finding the optimal timing for involvement.

Design/methodology/approach

Literature studies, interviews, workshops and focus-group meetings identified six main parameters essential for developing a method to determine the ideal timing for ECI.

Findings

The six identified parameters are activity, complexity, criticality, technical competencies, relational competencies and uncertainty. These parameters can be used to identify the gap between the available competency in the project team and the needed competency to perform an activity.

Originality/value

Although clients have ways to identify the optimal time for contractor involvement, these ways are mainly subjective and based on in-house practice. By evaluating these six parameters, a more systematic and objective method for early involvement can be developed.
Modeling the determinants of circular procurement adoption for sustainable construction: a fuzzy logic-based evaluation approach
Authors: Ababio Benjamin Kwaku , Lu Weisheng
Published: December 2024

Purpose

Traditional procurement approaches are no longer sufficient amidst dire environmental challenges caused by the construction sector. Yet, it is unclear from existing studies what factors could encourage alternatives such as circular procurement (CP). Thus, this study aims to investigate the determinants of CP adoption in the global construction industry.

Design/methodology/approach

The study employs a mixed-method approach involving focus group interviews with circular experts and engaging 194 international construction professionals using a questionnaire survey. Multiple statistical techniques, including exploratory factor analysis and fuzzy synthetic modelling, were employed to analyze the data.

Findings

The study identified fourteen key benefits that drive the adoption of CP practices in construction, with “Waste management throughout the construction lifecycle,” “Integration of supply chains” and “Opportunities from new business models” as the three most significant. However, a deeper analysis of the interconnections between these drivers revealed four clusters of principal benefit drivers (PBDs). The four principal groups were “lifecycle cost optimization,” “climate impact mitigation,” “circular capability and waste reduction” and “supply chain collaboration.” Through fuzzy synthetic modeling, it was predicted that three out of four PBDs exerted high levels of influence and should be prioritized for developed economies, while all four PBDs had significant levels of influence in developing regions.

Practical implications

The findings provide a useful reference point for policymakers, practitioners and researchers in formulating strategies to accelerate the adoption and implementation of CP practices in different construction industries.

Originality/value

The study provides a novel perspective on CP adoption through understanding and promotion of its benefits. This offers a valuable framework for decision-making in two regional contexts.