bluuebunny/crossref_metadata_2025_split huggingface dataset:
Similarities and differences in the gene expression signatures of physiological age versus future lifespan
Authors: Mosley Matthew C. , Kinser Holly E. , Martin Olivier M. F. , Stroustrup Nicholas , Schedl Tim , Kornfeld Kerry , Pincus Zachary 
Published: December 2024

AbstractAcross all taxa of life, individuals within a species exhibit variable lifespans. Differences in genotype or environment are not sufficient to explain this variance, as even isogenic Caenorhabditis elegans nematodes reared under uniform conditions show significant variability in lifespan. To investigate this phenomenon, we used lifespan‐predictive biomarkers to isolate, at mid‐adulthood, prospectively long‐ and short‐lived individuals from an otherwise identical population. We selected two biomarkers which correlated positively with lifespan, lin‐4p::GFP and mir‐243p::GFP, and two which correlated negatively, mir‐240/786p::GFP and autofluorescence. The gene‐expression signature of long versus short future lifespan was strikingly similar across all four biomarkers tested. Since these biomarkers are expressed in different tissues, these results suggest a shared connection to a global health state correlated with future lifespan. To further investigate this underlying state, we compared the transcriptional signature of long versus short future lifespan to that of chronologically young versus old individuals. By comparison to a high‐resolution time series of the average aging transcriptome, we determined that subpopulations predicted to be long‐ or short‐lived by biomarker expression had significantly different transcriptional ages despite their shared chronological age. We found that this difference in apparent transcriptional age accounted for the majority of differentially expressed genes associated with future lifespan. Interestingly, we also identified several genes whose expression consistently separated samples by biomarker expression independent of apparent transcriptional age. These results suggest that the commonalities in the long‐lived versus short‐lived state reported across different biomarkers of aging extends beyond simply transcriptionally young versus transcriptionally old.
Estradiol deficiency as a consequence of aging contributes to the depletion of the satellite cell pool in female mice
Authors: Sullivan Brian P. , Larson Alexie A. , Shams Ahmed S. , McMillin Shawna L. , Ebeling Mara C. , Peng Sydney , Kyba Michael , Lowe Dawn A. 
Published: December 2024

AbstractThe effects of aging on the satellite cell pool have primarily been studied in male mice, where the role of cell‐intrinsic versus environmental changes on satellite cell function remains contentious. Estradiol is necessary for maintenance of satellite cell pool size in adult female mice—here we investigate the hypothesis that in females, estradiol is a major environmental driver of age‐associated effects on satellite cells. In 24–26 month‐old ovarian senescent mice, we find the satellite cell pool size is severely diminished in certain muscles (TA and EDL) but only marginally affected in others (soleus and gastrocnemius). Supplementation with 17‐beta estradiol significantly increases satellite cell pool size in the TA and EDL. To assess cell‐intrinsic versus environmental regulation, we perform two transplantation experiments, Adult or Aged satellite cells transplanted into Adult recipients, and Adult satellite cells transplanted into Adult or Aged mice. These results demonstrate that the aged environment dominates over cell‐autonomous age in terms of the specification of satellite cell pool size. Transcriptional profiling on satellite cells from Adult, Aged and ovariectomized mice revealed commonalities across the two estradiol‐deficient conditions, Aged and ovariectomized, in GO terms from differentially expressed genes. Our findings support the hypothesis that the lack of estradiol contributes to reductions in satellite cell number in Aged female muscle, yet cells that remain are functional in terms of proliferative potential and self‐renewal capacity. These findings have implications for sex hormone treatment of menopausal women and highlight the vital role of estradiol in the maintenance of the satellite cell pool.
Allergen‐Specific Immunotherapy and Trained Immunity
Authors: Martín‐Cruz Leticia , Palomares Oscar 
Published: December 2024

ABSTRACTThe high prevalence of allergic diseases reached over the last years is attributed to the complex interplay of genetic factors, lifestyle changes, and environmental exposome. Allergen‐specific immunotherapy (AIT) is the single therapeutic strategy for allergic diseases with the potential capacity to modify the course of the disease. Our knowledge of the mechanisms involved in allergy and successful AIT has significantly improved. Recent findings indicate that long‐term allergen tolerance upon AIT discontinuation not only relies on the generation of proper adaptive immune responses by the generation of allergen‐specific regulatory T and B cells enabling the induction of different isotypes of blocking antibodies but also relies on the restoration of proper innate immune responses. Trained immunity (TRIM) is the process by which innate immune cells acquire memory by mechanisms depending on metabolic and epigenetic reprogramming, thus conferring the host with increased broad protection against infection. This concept was initially explored for infectious diseases, as well as for vaccination against infections, but compelling experimental evidence suggests that TRIM might also play a role in allergy and AIT. Hyperinflammatory innate immune responses in early life, likely due to TRIM maladaptations, lead to aberrant type 2 inflammation‐enhancing allergy. However, exposure to farming environments and specific microbes prevents recurrent infections and allergy development, likely due to mechanisms partially depending on TRIM. TRIM‐based vaccines and next‐generation AIT vaccines inducing metabolic and epigenetic reprogramming in innate immune cells and their precursors have shown protective antiallergic effects. A better understanding of the factors involved in early‐life TRIM mechanisms in the context of allergy and the identification and characterization of novel tolerance inducers might well enable the design of alternative TRIM‐based allergen vaccines for allergic diseases.
Treatment patterns in metastatic early‐onset rectal cancer
Authors: Thompson Nasya , Waddell Oliver , McCombie Andrew , Frizelle Francis , Glyn Ms Tamara 
Published: December 2024

AbstractBackgroundEarly onset rectal cancer (EORC) is increasing internationally. While EORC cancer presents with some distinct clinical features, there is currently insufficient evidence that age of onset should alter treatment. This study examines treatment patterns for EO versus late‐onset (LO) metastatic rectal cancer in Canterbury, New Zealand, to better understand appropriate treatment strategies and there effect on patient outcomes.MethodsA retrospective study on all patients diagnosed with stage 4 rectal adenocarcinoma in Canterbury from 2010 to 2021 was undertaken. Patients under 50 were compared to a control group aged 60–74, analysing treatment patterns, hospital stays, and survival outcomes.ResultsBetween 2010 and 2021, there were 949 rectal cancer diagnoses in Canterbury, of which 23 were EO and 64 were LO with stage 4 cancer. Survival analysis revealed a significant difference in median survival times between EORC (47.9 months) and LORC patients (26.5 months; P = 0.03). There was no significant difference in the surgical or oncological management between age groups (P > 0.05). Mean admissions per 100 days of life was 0.45 in LORC and 0.44 in EORC (P = 0.9119). There was no significant difference in the median proportion of time spent in hospital between EO and LO groups (2.5 vs. 2.2 days for every 100 days of life, P = 0.88).ConclusionSurgical and oncological treatments were similar for both EORC and LORC groups. The EO group exhibited better survival, with hospitalization burdens comparable for both. These findings underline the importance of maintaining an approach to metastatic RC balancing survival and quality of life.
Clinicians' views on implementing enhanced recovery after surgery: a descriptive qualitative study
Authors: Tobiano Georgia , Liang Rhea , Chaboyer Wendy , Lovegrove Josephine , Addy Keith , Gillespie Brigid M 
Published: December 2024

AbstractBackgroundEnhanced recovery after surgery (ERAS) protocols have existed for the past three decades; these protocols may improve patient outcomes and healthcare costs. Yet, ERAS is difficult to implement, and there has been limited focus on processes used to promote ERAS use. Thus, the aim of this study was to identify and describe the barriers and enablers to implementing ERAS.MethodsIn this qualitative descriptive sub‐study, semi‐structured interviews, guided by the Theoretical Domains Framework, were conducted with surgeons, anaesthetists, and nurses. Interviews were analyzed using inductive and deductive content analysis.ResultsThree categories were found, which mapped to 12 domains in the Theoretical Domains Framework. Category 1 ‘realizing the value of ERAS, despite varying levels of exposure and motivation’ showed clinicians' different views and knowledge towards ERAS, with a general belief that ERAS was evidence‐based. Category 2, ‘building momentum for ERAS implementation’ outlined strategies to encourage clinicians to practice ERAS. The final category ‘providing resources for ERAS’ illustrated the tools and up‐front costs needed for ERAS implementation.ConclusionMotivational strategies are required to inspire individual clinicians to adopt ERAS. Additionally, resources are needed for ERAS to guide practice and support implementation (i.e., staffing and time), underscoring the need for hospital leadership support.
Physiological impact of oral carbohydrate preload in healthy volunteers
Authors: Cowie Brian , Lipszyc Adam , Luxford Jamahal , Devapalasundaram Abarna , Dubey Harsh , Kluger Roman , Phan Tuong 
Published: December 2024

AbstractBackgroundOral carbohydrate loading has become a key component of Enhanced Recovery After Major Surgery (ERAS) pathways, with potential improvements in patient comfort, nausea and vomiting, ileus and length of stay. The contribution of each component of ERAS, including carbohydrate beverages, remains unclear. We aimed to determine the impact of standardized oral carbohydrate fluid loading on haemodynamics, stroke volume and gastric state in a group of healthy volunteers.MethodsTwenty‐three volunteer participants free of known cardiovascular or gastrointestinal disease, consumed 400 mL of a proprietary carbohydrate solution. Heart rate (HR), blood pressure (BP), stroke volume (SV) and gastric cross‐sectional area (CSA) were measured with bedside ultrasound at baseline, 30/60/120 min post‐ingestion.ResultsThere were small decreases in HR, BP (<10%) that were statistically significant. There were small increases (<10%) in SV at 30 and 60 min post‐ingestion, but SV had returned to baseline by 120 min. There were no changes in SV variation. Gastric CSA increased immediately post‐ingestion, then decreased in a linear fashion before returning to baseline by 120 min.ConclusionIn a standard 400 mL dose of a carbohydrate beverage, only small increases in SV could be demonstrated in the first‐hour post‐ingestion. All patients had largely returned to their baseline SV and gastric CSA state within 2 h post‐fluid ingestion. A mild decrease in HR and BP was noted that persisted at 120 min. A 400 mL carbohydrate beverage does not appear to have favourable cardiovascular effects in a healthy population.
Toward human uterus tissue engineering: Uterine decellularization in a non‐human primate species
Authors: De Miguel‐Gómez Lucía , Sehic Edina , Thorén Emy , Ahlström Johan , Rabe Hardis , Oltean Mihai , Brännström Mats , Hellström Mats 
Published: December 2024

AbstractIntroductionUterus bioengineering offers a potential treatment option for women with uterine factor infertility and for mitigating the risk of uterine rupture associated with women with defective uterine tissue. Decellularized uterine tissue scaffolds proved promising in further in vivo experiments in rodent and domestic species animal models. Variations in the extracellular matrix composition among different species and adaptations of the decellularization protocols make it difficult to compare the results between studies. Therefore, we assessed if our earlier developed sodium deoxycholate‐based decellularization protocol for the sheep and the cow uterus could become a standardized cross‐species protocol by assessing it on the non‐human primate (baboon) uterus.Material and MethodsThe baboon uterus was decellularized using sodium deoxycholate, and the remaining acellular scaffold was quantitatively assessed for DNA, protein, and specific extracellular matrix components. Furthermore, electron microscopy deepened morphology examination, while the chorioallantoic membrane assay examined the scaffolds' cytotoxicity, bioactivity, and angiogenic properties. The in vitro recellularization efficiency of the scaffolds using xenogeneic (rat) bone marrow‐derived mesenchymal stem cells was also assessed. Finally, the immune potential of the scaffolds was evaluated by in vitro exposure to human peripheral blood mononuclear cells.ResultsWe obtained a decellularized baboon uterus with preserved extracellular matrix components by adding an 8‐h sodium deoxycholate perfusion to our previously developed protocol for the sheep and cow models. This minor modification resulted in scaffolds with less than 1% of immunogenic host DNA content while preserving important uterine‐specific collagen, elastin, and glycosaminoglycan structures. The chorioallantoic membrane assay and in vitro recellularization experiments confirmed that the scaffolds were bioactive and non‐cytotoxic. As we have observed in other animal models, the enzymatic scaffold preconditioning with matrix metalloproteinases improved the recellularization efficiency further. Additionally, the preconditioning generated more immune‐privileged scaffolds, as shown in a novel in vitro co‐culture assay with human peripheral blood mononuclear cells.ConclusionsFor the first time, our data demonstrate the efficiency of our protocol for non‐human primate uteri and its translational potential. This standardized protocol will facilitate cross‐study comparisons and expedite clinical translation.
Growth hormone treatment in children in Israel: A large‐scale retrospective database study
Authors: Reichenberg Yael , Bello Rachel , Oberman Bernice , Cohen Moryia , Cohen Avner Herman , Shkalim Zemer Vered 
Published: December 2024

AbstractAimTo evaluate the indications, population characteristics and latency between short stature diagnosis to treatment with recombinant growth hormone (GH) therapy in a large cohort of children in Israel.MethodsWe performed a retrospective medical chart review of all children treated with GH for conditions associated with short stature in three central districts in Israel from 1 January 2010 to 31 December 2021. Data extracted from the medical files included demographics, time to diagnosis, treatment indications and GH therapy duration.ResultsThe study group comprised 5148 children aged 1 day to 17 years. A total of 64.1% were diagnosed with idiopathic short stature (ISS), 31.1% with GH deficiency (GHD) and 2.5% with small‐for‐gestational age (SGA). Males were treated more than females (58.9% vs. 41.1%). The mean age at first documentation of short stature was 6.9 ± 3.5 years. GH therapy was initiated at a mean age of 9.8 ± 3.3 years. A total of 51.2% were of high socio‐economic status (SES); 78.2% were non‐ultraorthodox Jews, 13%, ultraorthodox Jews, and 8.8% were Arabs.ConclusionMeticulous growth follow‐up from early childhood for all children, specifically females, those of low SES, and minorities is important to provide appropriate referral, treatment and final adult height outcomes.
EcoFloVCS: An eco‐physiognomic‐floristic vegetation classification system
Authors: Song Kun , Zhang Jian , Yan Enrong , Wang Xihua , Song Yongchang 
Published: December 2024

AbstractBackgroundVegetation science research has been conducted for approximately 200 years; however, until now there has not been a unified classification principle or system that was acceptable to vegetation scientists. To facilitate the development of vegetation science and its applications in natural conservation, a unified vegetation classification system is urgently required. Here we propose a unified eco‐physiognomic‐floristic vegetation classification system (EcoFloVCS) that combines eco‐physiognomic and floristic characteristic classification systems.MethodsUnder the EcoFloVCS, plant communities are considered to have six key components (species composition, structure, habitat, development, locality, and function). Six associated characteristics are derived from these six components (dominant species, diagnostic species, physiognomy, distribution patterns, dynamics, and disturbance processes). These characteristics are used as the basis for community classification.Results and ConclusionsThe high‐level units of this system agree with the UNESCO system, whereas the middle‐ and low‐level units correspond to the Braun‐Blanquet classification system. Both are connected by a Division (Subformation) unit. Based on the EcoFloVCS, a vegetation system was constructed for the four highest units worldwide that included seven Formation Classes, 22 Formation Subclasses, 39 Formation Groups, and 119 Formations. We assume that vegetation science will benefit from our unified EcoFloVCS through comparing and understanding community structures and functions on a global scale.
Effect of CAD/CAM Abutment Morphology on the Outcomes of Implant Therapy: A Randomized Controlled Trial
Authors: Barwacz Christopher A. , Swenson Madeline , Couso‐Queiruga Emilio , Comnick Carissa , Xie Xian Jin , Avila‐Ortiz Gustavo 
Published: December 2024

ABSTRACTObjectivesVariations in transmucosal abutment contour design may affect the outcomes of implant therapy. This randomized controlled trial was primarily aimed at testing the effect that CAD/CAM zirconia abutments with either a concave or linear divergent transmucosal morphology have on peri‐implant mucosal dynamics and indicators of peri‐implant health at 1 year after final implant‐supported prosthesis insertion in the anterior maxilla.Materials and MethodsFollowing computer‐guided implant placement and osseointegration, eligible subjects were randomized into either the experimental (concave morphology) or the control (linear divergent morphology) group. A comprehensive set of outcomes of interest related to peri‐implant soft tissue dynamics, phenotypical features, and indicators of peri‐implant health were assessed at different time points over a 1‐year period after insertion of the final restoration.ResultsOut of 60 initially recruited subjects, a total of 54 completed the study (n = 29 in the experimental group concave/n = 25 in the control group). Overall implant survival and restoration rates between master impression and 12 months were 100% and 98.2%, respectively. Although a trend for coronal migration of the buccal mucosa zenith, gain in mucosal thickness, and increased probing depth and bleeding on probing was observed in both groups, these changes were clinically negligible, and no substantial differences were observed between study groups regardless of variations in transmucosal abutment morphology.ConclusionThe use of either linear divergent or concave custom CAD/CAM zirconia abutments in a screw‐retained, delayed loading approach yielded no significant differences.
Multivariate Regression Models for Predicting the Prognosis of Luxation Injuries of Permanent Teeth: Periodontal and Pulp Analyses
Authors: Yu Haojie , Li Xiaoxia , Feng Bin , Yu Sang , Wang Qingjing , Zhu Fudong , Zhu Haihua 
Published: December 2024

ABSTRACTBackgroundThis study aimed to analyse the relationships between injury variables, treatment variables and the status of the periodontium or pulp of luxated teeth.Materials and MethodsThe electronic medical records and imaging data of patients who underwent treatment for luxation injuries of permanent teeth in the paediatric dentistry and dental emergency departments of the Stomatology Hospital, Zhejiang University School of Medicine between 1 January 2012 and 1 January 2022 were retrospectively analysed. First, the patients' records were reviewed to collect background and follow‐up imaging data; then, all early clinical variables were reviewed and used to construct models to predict the periodontal and pulp status of the luxated teeth. The models included the significant factors identified in the univariate analysis, and multivariate analysis was performed to evaluate the relationships between the variables and the final status of the periodontium or dental pulp. The chi‐square test and Fisher's exact test were employed to analyse the differences in the frequency of each variable. The variables were systematically screened based on their odds ratios, and significance levels were determined by Pearson's chi‐square test.ResultsA total of 188 patients were initially identified and ultimately included. The age range of the patients was 7–56 years. Logistic regression models for periodontal and pulp prognosis of the luxated teeth were established. The models were refined by combining the results of feature selection, parameter testing and goodness‐of‐fit testing. The final model included four variables and accurately predicted the periodontal outcome in 65.79% of the cases. The prognostic model for the dental pulp included three significant factors and had an overall accuracy of 94.59%.ConclusionThe prognostic models developed to predict the influence of various factors on the status of the periodontium and dental pulp of luxated teeth demonstrated notable accuracy and practical utility. Therefore, these models are potentially valuable tools for long‐term prognostic assessments.Trial RegistrationApproval no. ChiCTR2100044897
Venetoclax in the Treatment of Multiple Myeloma: A Retrospective Analysis of 79 Patients
Authors: Zolotov Eli , Patel Vanisha , Weiss Yedidyah , Biran Noa , Phull Pooja , Vesole David H. , Siegel David S. , Parmar Harsh 
Published: December 2024

ABSTRACTVenetoclax, the first‐in‐class BCL‐2 inhibitor, has shown efficacy in multiple myeloma (MM), particularly in patients with the t(11;14) translocation. This single‐center retrospective analysis included MM patients treated with venetoclax from November 2017 to March 2023. Data encompassed demographics, disease characteristics, treatment regimens, and outcomes using median progression‐free‐survival (mPFS). Eligibility required patients to be aged 21 and older and to have received at least one venetoclax cycle. Seventy‐nine patients (median age 61, 58.2% female) were included, with 31.6% having t(11;14). Patients had received a median of 5 lines of therapy (LOT) before venetoclax. The mPFS was 3.4 months, with a significant difference between t(11;14) positive (7.8 months) and negative patients (2.4 months, p < 0.01). Patients achieving a very good partial response or better had a mPFS of 7.1 months. Common adverse events included fatigue (31.6%), diarrhea (26.5%), and respiratory infections (30.3%). Univariable and multivariable analyses identified sex, disease response, and t(11;14) presence as significant survival predictors. Our real‐world study suggests that venetoclax demonstrates moderate efficacy in heavily pretreated patients with relapsed/refractory MM (RRMM), compared to previous studies where patients received 1–3 prior LOT, such as the BELLINI study (mPFS of 22.4 months). Notably, the efficacy was higher in patients with t(11;14). Despite the heavily pretreated nature of our cohort, venetoclax was well tolerated, with a manageable safety profile and low incidence of severe infections, largely due to effective prophylactic measures. Venetoclax should be carefully considered in heavily pretreated populations, and further multicenter research is essential to better define its role in RRMM.