bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and clinical validation of key genes as the potential biomarkers in colorectal adenoma
Authors: Wang Bangting , Zhang Jiting , Wang Xin , Zhao Lili , Wang Yan , Fan Zhining , Liu Li , Gao Wenqing 
Published: January 2023

Abstract
Background
Colorectal cancer (CRC), ranking third in cancer prevalence and second in mortality worldwide, is mainly derived from colorectal adenoma (CRA). CRA is a common benign disease in the intestine with rapidly increasing incidence and malignant potential. Therefore, this study aimed to recognize significant biomarkers and original pathogenesis in CRA.

Methods
Transcriptome data of GSE8671, GSE37364, and GSE15960 were downloaded from the Gene Expression Omnibus (GEO) datasets, and differentially expressed genes (DEGs) were screened. Functional pathways enrichment, protein–protein interaction (PPI) network, stem-correlation analysis, CIBERSORT, risk score and survival analyses were performed. RT-qPCR and immunohistochemical staining were applied to verify our results.

Results
Screening for significant DEGs in each dataset, we identified 230 robust DEGs, including 127 upregulated and 103 downregulated genes. Functional pathways enrichment showed that these DEGs were distinctly enriched in various tumor-associated pathways, such as growth factor activity, extracellular structure organization, neutrophil activation, and inflammatory response. We filtered out two hub genes via STRING and Modules analysis, including CA2 and HSD11B2. Stem-correlation analysis displayed that hub genes were negatively associated with stem-related genes (Olfm4, CD44, CCND1 and MYC). The CIBERSORT algorithm indicated that Macrophage2, activated mast cells, and Neutrophils promoted CRA progression through inflammation. Survival analysis showed that CA2 and HSD11B2 were positively associated with survival outcomes in CRC.

Conclusion
Our study has successfully identified the critical role of two core genes in the development and oncogenesis of CRA, which provides novel insight into the underlying pathogenesis, potential biomarkers and therapeutic targets.
Study protocol of the sweet tooth study, randomized controlled trial with partial food provision on the effect of low, regular and high dietary sweetness exposure on sweetness preferences in Dutch adults
Authors: Čad Eva M. , Tang Claudia S. , de Jong Hanne B. T. , Mars Monica , Appleton Katherine M. , de Graaf Kees 
Published: January 2023

Abstract
Background
Several health organizations recommend lowering the consumption of sweet-tasting foods. The rationale behind this recommendation is that a lower exposure to sweet foods may reduce preferences for sweet tasting foods, thus lowering sugar and energy intake, and in turn aiding in obesity prevention. However, empirical data supporting this narrative are lacking. In fact, relatively little is known about the contribution of long-term sweet taste exposure on one’s sweetness preferences.

Methods
The primary objective of this randomized controlled trial is to assess the effect of low, regular and high dietary sweetness exposure on preference for sweet foods and beverages, and to compare these effects between intervention groups. One hundred and eighty adults aged 18–65 years with a BMI of 18.5–30.0 kg/m2 will be recruited and randomly allocated to either: low dietary sweetness exposure (LSE) (10–15% daily energy from sweet tasting foods), regular dietary sweetness exposure (RSE) (25–30% daily energy from sweet tasting foods), or high dietary sweetness exposure (HSE) (40–45% daily energy from sweet tasting foods), for 6 months, followed by a 4-month follow up. Intervention foods are provided ad libitum, covering approximately 50% of the daily number of food items, to include sugar-sweetened, low-calorie-sweetener-sweetened and non-sweet foods. The primary outcome measure is the difference in change in sweetness preference from baseline to 6 months between intervention groups. Secondary outcomes include: change in sweet taste preferences at different time-points; taste intensity perception; behavioral outcomes: food choice and intake, sweet-liker type, food cravings, dietary taste preferences and dietary taste patterns; anthropometric outcomes: body composition, waist-hip circumference, body weight; and biochemical outcomes: glucose variability and biomarkers related to CVD and diabetes.

Discussion
This study will generate important data on the effect of dietary sweetness exposure on sweetness preferences in terms of effect size and change, duration of change and its impact on food intake, body weight status and associated health outcomes.

Trial Registration
The study protocol has been registered on ClinicalTrials.gov (ID no. NCT04497974, Registered 4 August 2020, https://clinicaltrials.gov/ct2/show/NCT04497974) and approved by Wageningen’s Medical Ethical Committee (ABR no. NL72134).
Cost-utility analysis and net monetary benefit of Platelet Rich Plasma (PRP), intra-articular injections in compared to Plasma Rich in Growth Factors (PRGF), Hyaluronic Acid (HA) and ozone in knee osteoarthritis in Iran
Authors: Raeissadat Seyed Ahmad , Rahimi Mohammad , Rayegani Seyed Mansoor , Moradi Najmeh 
Published: January 2023

Abstract
Purpose
To evaluate the cost-effectiveness of Platelet Rich Plasma (PRP), Plasma Rich in Growth Factors (PRGF), Hyaluronic Acid (HA) and ozone as effective treatment approaches in knee osteoarthritis management from Iran Health care perspective.

Methods
A decision tree model was conducted to assess the cost-effectiveness of four common intra-articular treatment approaches in patients with mild and moderate knee osteoarthritis. The data on clinical effectiveness was obtained from a randomized controlled trial (RCT) conducted in Iran and used to estimate utility values. The direct medical costs were estimated according to tariffs for public medical centers and hospitals, approved by the Iran Ministry of Health and Medical Education in 2021. The incremental cost-effectiveness ratio (ICER) and the net monetary benefit (NMB) were used to evaluate the cost-utility analysis. Deterministic and probabilistic sensitivity analyses are performed to investigate the robustness of the results and account for the different sources of uncertainty.

Results
In this study, HA intra-articular injection-related costs ($581.67/patient) were defined as the highest cost, followed by PRGF ($328.10/patient), PRP (318.58/patient), and Ozone (103.20/patient). According to the utility value, PRP and PRGF (0.68) have the same and the most utility among Intra-articular injections in knee osteoarthritis management. However, the PRP injection method was identified as the most cost-effective intervention due to its high NMB and ICER estimates. Based on the Monte Carlo Simulation, PR intervention, compared to other ones, was introduced as the dominant strategy regarding knee OA management, with a WTP of $10,000 for 100% of cases.

Conclusion
The study result demonstrated that intra-articular injection of PRP, compare to other injections, is a cost-effective treatment option for patients with mild and moderate knee osteoarthritis. In addition, intra-articular injection of PRP was identified as the best injection, with the highest level of net monetary benefit, for knee OA management.
Type 1 diabetes, periodontal health, and a familial history of hyperlipidaemia is associated with oral microbiota in children: a cross-sectional study
Authors: Selway Caitlin A. , Jensen Emilija D. , Pena Alexia S. , Smart Gabrielle , Weyrich Laura S. 
Published: January 2023

Abstract
Background
Hyperlipidaemia may play a significant role in the interrelationship between type 1 diabetes (T1D) and periodontal disease. A potential mechanism that links these three aspects together is the oral microbiota. We wanted to determine if there is an association between hyperlipidaemia, periodontal disease, and the oral microbiota of children with T1D, as this has not yet been explored.

Methods
In a post-hoc, cross-sectional study using 16S rRNA gene sequencing, we explored links between oral bacterial diversity and composition of gingival swab samples from 72 children with T1D to periodontal risk factors and hyperlipidaemia status of first-degree relatives. While multiple periodontal risk factors were assessed, we used periodontal pocket depth of 3 mm to characterise periodontal risk. As periodontal pocket depth confounded the analysis of familial history of hyperlipidaemia, a multivariate analyses were performed (i.e., no periodontal risk markers in children with or without a family history of hyperlipidaemia were compared to counterparts who did not have periodontal risk markers) to examine linkages between these factors and diversity and composition of the microbiome.

Results
In participants with no periodontitis risk, children with a family history of dyslipidemia had different bacterial diversity and composition compared to those without a familar hisitory. In contrast, such differences did not exist in the children with periodontal risk, whether or not they had a family history of hyperlipidaemia. Co-occurrence networks showed that these differences in children with no periodontists risk were linked to the presence of fewer oral microbial networks, but more microbes linked to mature plaque structures. In contrast, children with periodontal risk markers, regardless of family history of hyperlipidaemia, contained co-occurrence networks that were associated with microbes linked to periodontal disease.

Conclusions
In children diagnosed with T1D, our findings support an association between oral microbiota and two different exposure variables: familial history of hyperlipidaemia and periodontal risk factors.
Olfactory sensitivity differentiates morphologically distinct worker castes in Camponotus floridanus
Authors: Ferguson S. T. , Bakis I. , Edwards N. D. , Zwiebel L. J. 
Published: January 2023

Abstract
Background
Camponotus floridanus ant colonies are comprised of a single reproductive queen and thousands of sterile female offspring that consist of two morphologically distinct castes: smaller minors and larger majors. Minors perform most of the tasks within the colony, including brood care and food collection, whereas majors have fewer clear roles and have been hypothesized to act as a specialized solider caste associated with colony defense. The allocation of workers to these different tasks depends, in part, on the detection and processing of local information including pheromones and other chemical blends such as cuticular hydrocarbons. However, the role peripheral olfactory sensitivity plays in establishing and maintaining morphologically distinct worker castes and their associated behaviors remains largely unexplored.

Results
We examined the electrophysiological responses to general odorants, cuticular extracts, and a trail pheromone in adult minor and major C. floridanus workers, revealing that the repertoire of social behaviors is positively correlated with olfactory sensitivity. Minors in particular display primarily excitatory responses to olfactory stimuli, whereas major workers primarily manifest suppressed, sub-solvent responses. The notable exception to this paradigm is that both minors and majors display robust, dose-dependent excitatory responses to conspecific, non-nestmate cuticular extracts. Moreover, while both minors and majors actively aggress non-nestmate foes, the larger and physiologically distinct majors display significantly enhanced capabilities to rapidly subdue and kill their adversaries.

Conclusions
Our studies reveal the behavioral repertoire of minors and majors aligns with profound shifts in peripheral olfactory sensitivity and odor coding. The data reported here support the hypothesis that minors are multipotential workers with broad excitatory sensitivity, and majors are dedicated soldiers with a highly specialized olfactory system for distinguishing non-nestmate foes. Overall, we conclude that C. floridanus majors do indeed represent a physiologically and behaviorally specialized soldier caste in which caste-specific olfactory sensitivity plays an important role in task allocation and the regulation of social behavior in ant colonies.
Intra-colony venom diversity contributes to maintaining eusociality in a cooperatively breeding ant
Authors: Robinson Samuel D. , Schendel Vanessa , Schroeder Christina I. , Moen Sarah , Mueller Alexander , Walker Andrew A. , McKinnon Naomi , Neely G. Gregory , Vetter Irina , King Glenn F. , Undheim Eivind A. B. 
Published: January 2023

Abstract
Background
Eusociality is widely considered to evolve through kin selection, where the reproductive success of an individual’s close relative is favored at the expense of its own. High genetic relatedness is thus considered a prerequisite for eusociality. While ants are textbook examples of eusocial animals, not all ants form colonies of closely related individuals. One such example is the ectatommine ant Rhytidoponera metallica, which predominantly forms queen-less colonies that have such a low intra-colony relatedness that they have been proposed to represent a transient, unstable form of eusociality. However, R. metallica is among the most abundant and widespread ants on the Australian continent. This apparent contradiction provides an example of how inclusive fitness may not by itself explain the maintenance of eusociality and raises the question of what other selective advantages maintain the eusocial lifestyle of this species.

Results
We provide a comprehensive portrait of the venom of R. metallica and show that the colony-wide venom consists of an exceptionally high diversity of functionally distinct toxins for an ant. These toxins have evolved under strong positive selection, which is normally expected to reduce genetic variance. Yet, R. metallica exhibits remarkable intra-colony variation, with workers sharing only a relatively small proportion of toxins in their venoms. This variation is not due to the presence of chemical castes, but has a genetic foundation that is at least in part explained by toxin allelic diversity.

Conclusions
Taken together, our results suggest that the toxin diversity contained in R. metallica colonies may be maintained by a form of group selection that selects for colonies that can exploit more resources and defend against a wider range of predators. We propose that increased intra-colony genetic variance resulting from low kinship may itself provide a selective advantage in the form of an expanded pharmacological venom repertoire. These findings provide an example of how group selection on adaptive phenotypes may contribute to maintaining eusociality where a prerequisite for kin selection is diminished.
Predicting mortality in acutely hospitalised older patients: the impact of model dimensionality
Authors: Tsui Alex , Tudosiu Petru-Daniel , Brudfors Mikael , Jha Ashwani , Cardoso Jorge , Ourselin Sebastien , Ashburner John , Rees Geraint , Davis Daniel , Nachev Parashkev 
Published: January 2023

Abstract
Background
The prediction of long-term mortality following acute illness can be unreliable for older patients, inhibiting the delivery of targeted clinical interventions. The difficulty plausibly arises from the complex, multifactorial nature of the underlying biology in this population, which flexible, multimodal models based on machine learning may overcome. Here, we test this hypothesis by quantifying the comparative predictive fidelity of such models in a large consecutive sample of older patients acutely admitted to hospital and characterise their biological support.

Methods
A set of 804 admission episodes involving 616 unique patients with a mean age of 84.5 years consecutively admitted to the Acute Geriatric service at University College Hospital were identified, in whom clinical diagnoses, blood tests, cognitive status, computed tomography of the head, and mortality within 600 days after admission were available. We trained and evaluated out-of-sample an array of extreme gradient boosted trees-based predictive models of incrementally greater numbers of investigational modalities and modelled features. Both linear and non-linear associations with investigational features were quantified.

Results
Predictive models of mortality showed progressively increasing fidelity with greater numbers of modelled modalities and dimensions. The area under the receiver operating characteristic curve rose from 0.67 (sd = 0.078) for age and sex to 0.874 (sd = 0.046) for the most comprehensive model. Extracranial bone and soft tissue features contributed more than intracranial features towards long-term mortality prediction. The anterior cingulate and angular gyri, and serum albumin, were the greatest intracranial and biochemical model contributors respectively.

Conclusions
High-dimensional, multimodal predictive models of mortality based on routine clinical data offer higher predictive fidelity than simpler models, facilitating individual level prognostication and interventional targeting. The joint contributions of both extracranial and intracranial features highlight the potential importance of optimising somatic as well as neural functions in healthy ageing. Our findings suggest a promising path towards a high-fidelity, multimodal index of frailty.
Recommendations for robust and reproducible preclinical research in personalised medicine
Authors: Fosse Vibeke , Oldoni Emanuela , Bietrix Florence , Budillon Alfredo , Daskalopoulos Evangelos P. , Fratelli Maddalena , Gerlach Björn , Groenen Peter M. A. , Hölter Sabine M. , Menon Julia M. L. , Mobasheri Ali , Osborne Nikki , Ritskes-Hoitinga Merel , Ryll Bettina , Schmitt Elmar , Ussi Anton , Andreu Antonio L. , McCormack Emmet ,   on behalf of The PERMIT group, Banzi Rita , Demotes Jacques , Garcia Paula , Gerardi Chiara , Glaab Enrico , Haro Josep Maria , Hulstaert Frank , Miguel Lorena San , Mirete Judit Subirana , Niubo Albert Sanchez , Porcher Raphaël , Rauschenberger Armin , Rodriguez Montserrat Carmona , Superchi Cecilia , Torres Teresa 
Published: January 2023

Abstract
Background
Personalised medicine is a medical model that aims to provide tailor-made prevention and treatment strategies for defined groups of individuals. The concept brings new challenges to the translational step, both in clinical relevance and validity of models. We have developed a set of recommendations aimed at improving the robustness of preclinical methods in translational research for personalised medicine.

Methods
These recommendations have been developed following four main steps: (1) a scoping review of the literature with a gap analysis, (2) working sessions with a wide range of experts in the field, (3) a consensus workshop, and (4) preparation of the final set of recommendations.

Results
Despite the progress in developing innovative and complex preclinical model systems, to date there are fundamental deficits in translational methods that prevent the further development of personalised medicine. The literature review highlighted five main gaps, relating to the relevance of experimental models, quality assessment practices, reporting, regulation, and a gap between preclinical and clinical research. We identified five points of focus for the recommendations, based on the consensus reached during the consultation meetings: (1) clinically relevant translational research, (2) robust model development, (3) transparency and education, (4) revised regulation, and (5) interaction with clinical research and patient engagement. Here, we present a set of 15 recommendations aimed at improving the robustness of preclinical methods in translational research for personalised medicine.

Conclusions
Appropriate preclinical models should be an integral contributor to interventional clinical trial success rates, and predictive translational models are a fundamental requirement to realise the dream of personalised medicine. The implementation of these guidelines is ambitious, and it is only through the active involvement of all relevant stakeholders in this field that we will be able to make an impact and effectuate a change which will facilitate improved translation of personalised medicine in the future.
Evaluation of a cluster-randomized controlled trial: Communities for Healthy Living, family-centered obesity prevention program for Head Start parents and children
Authors: Gago Cristina , Aftosmes-Tobio Alyssa , Beckerman-Hsu Jacob P. , Oddleifson Carly , Garcia Evelin A. , Lansburg Kindra , Figueroa Roger , Yu Xinting , Kitos Nicole , Torrico Merieka , Leonard Jessie , Jurkowski Janine K. , Mattei Josiemer , Kenney Erica L. , Haneuse Sebastien , Davison Kirsten K. 
Published: January 2023

AbstractBackgroundThis study reports the outcomes of Communities for Healthy Living (CHL), a cluster randomized obesity prevention trial implemented in partnership with Head Start, a federally-funded preschool program for low-income families.MethodsUsing a stepped wedge design, Head Start programs (n = 16; Boston, MA, USA) were randomly assigned to one of three intervention start times. CHL involved a media campaign and enhanced nutrition support. Parents were invited to join Parents Connect for Healthy Living (PConnect), a 10-week wellness program. At the beginning and end of each school year (2017-2019), data were collected on the primary outcome of child Body Mass Index z-score (BMIz) and modified BMIz, and secondary outcomes of child weight-related behaviors (diet, physical activity, sleep, media use) and parents’ weight-related parenting practices and empowerment. Data from 2 years, rather than three, were utilized to evaluate CHL due to the COVID-19 pandemic. We used mixed effects linear regression to compare relative differences during intervention vs. control periods (n = 1274 vs. 2476 children) in (1) mean change in child BMIz and modified BMIz, (2) the odds of meeting child health behavior recommendations, (3) mean change in parenting practices, and (4) mean change in parent empowerment. We also compared outcomes among parents who chose post-randomization to participate in PConnect vs. not (n = 55 vs. 443).ResultsDuring intervention periods (vs. control), children experienced greater increases in BMIz and modified BMIz (b = 0.06, 95% CI = 0.02,0.10;b = 0.07, 95% CI = 0.03, 0.12), yet were more likely to meet recommendations related to three of eight measured behaviors: sugar-sweetened beverage consumption (i.e., rarely consume; Odds Ratio (OR) = 1.5, 95% CI = 1.2,2.3), water consumption (i.e., multiple times per day; OR = 1.6, 95% CI = 1.2,2.3), and screen time (i.e., ≤1 hour/day; OR = 1.4, 95% CI = 1.0,1.8). No statistically significant differences for intervention (vs. control) periods were observed in parent empowerment or parenting practices. However, parents who enrolled in PConnect (vs. not) demonstrated greater increases in empowerment (b = 0.17, 95% CI = 0.04,0.31).ConclusionsInterventions that emphasize parent engagement may increase parental empowerment. Intervention exposure was associated with statistically, but not clinically, significant increases in BMIz and increased odds of meeting recommendations for three child behaviors; premature trial suspension may explain mixed results.Trial registrationClinicalTrials.gov,NCT03334669, Registered October 2017.