bluuebunny/crossref_metadata_2025_split huggingface dataset:
WNT4 promotes the symmetric fission of crypt in radiation-induced intestinal epithelial regeneration
Authors: Cheng Jingyang , Wu Haiyong , Cui Yanmei 
Published: December 2024

Abstract
Background
Radiotherapy for pelvic malignant tumors inevitably causes intestinal tissue damage. The regeneration of intestinal epithelium after radiation injury relies mainly on crypt fission. However, little is known about the regulatory mechanisms of crypt fission events.

Methods
The effects of WNT4 on crypt regeneration and the symmetry of crypt fission were examined using a mouse small intestinal organoid culture model. Three-dimensional (3D) reconstructed images of organoids were applied to assess the symmetry of crypt fission and Paneth cell localization upon manipulation of WNT4 expression. The effect of WNT4 on the expression of β-catenin target genes was analyzed by real-time quantitative polymerase chain reaction (RT-qPCR). The in vivo effect of WNT4 overexpression mediated by adeno-associated virus (AAV) on symmetric fission of crypt was investigated using a radiation-injured mouse model.

Results
WNT4 has a special function of promoting symmetric fission of small intestinal crypts, although it inhibits budding, stemness, and cell proliferation on organoids. WNT4 promotes the correct localization of Paneth cells in the crypt base by regulating the expression of EphB3, thereby promoting the symmetric fission of small intestinal crypts. WNT4 negatively regulates the canonical WNT/β-catenin signaling pathway, and it promotes symmetric crypt fission in a ROR2 receptor-dependent manner. Moreover, in patients and animal models of radiation-induced intestinal injury, we found that the regenerated crypts are irregular in size and shape, Paneth cells are mislocalized, and the expression of WNT4 is decreased while EphB3 is increased. Importantly, restoration of WNT4 expression mediated by AAV effectively promotes symmetric crypt fission and thus improves the regularity of regenerating crypts in mice with radiation-induced injury.

Conclusions
Our study highlights the critical role of WNT4 in the regulation of crypt fission and provides WNT4 as a potential therapeutic target for radiation enteritis.

Graphical Abstract
Comparative genomics and phylogenetic analysis of six Malvaceae species based on chloroplast genomes
Authors: Zhong Yiwang , Bai Beibei , Sun Yangyang , Wen Ke , Qiao Yang , Guo Lijun , Deng Huidong , Ye Yingjun , Feng Liying , Feng Xuejie 
Published: December 2024

AbstractThe Malvaceae family, comprising 9 subfamilies and 4,225 species, includes economically significant taxa, such as Ceiba pentandra, Gossypium ekmanianum, Gossypium stephensii, Kokia drynarioides, Talipariti hamabo, and Durio zibethinus. Chloroplast (cp) genome research is crucial for elucidating the evolutionary divergence and species identification within this family. In this study, we assembled and annotated cp genomes of six Malvaceae species, conducting comprehensive comparative genomic and phylogenomic analyses. The assembled genomes range from 160,495 to 163,970 bp in size, with 125–129 genes annotated. Notable differences were observed in the IR (inverted repeat) regions, and SSR analysis revealed that Durio zibethinus has the highest number of specific variation sites. Among the six species, Talipariti hamabo uniquely exhibits more palindromic repeats than forward repeats. Seven highly mutated regions were identified, offering potential markers for species identification. Phylogenetic reconstruction using the maximum likelihood method revealed two primary clades within Malvaceae: Byttneriina and Malvadendrina. Within Malvadendrina, the subfamily Helicteroideae represents the earliest divergence, followed by Sterculioideae. This study provides a robust phylogenetic framework and valuable insights into the classification and evolutionary history of Malvaceae species.
Conceiving during the first postoperative year after bariatric surgery: a retrospective study of pregnancy outcomes
Authors: Kaukonen Sesilia , Pajula Susanna , Gissler Mika , Juuti Anne , Ulander Veli-Matti , Kaijomaa Marja 
Published: December 2024

Abstract
Background
An increasing number of childbearing-aged women have undergone bariatric surgery (BS). Although pregnancy outcomes generally improve after BS, concern remains over the impact of rapid weight loss and the catabolic state that occurs soon after BS. At least a 12-month surgery-to-conception time (SCT) is recommended, though the reasoning behind this has been questioned. This retrospective study was conducted to compare post-BS pregnancies with SCTs of less (Group 1) or more (Group 2) than 12 months.

Methods
The Hospital Register and Finnish Medical Birth Register were queried for data on BS and subsequent pregnancies. The characteristics of women at surgery and maternal and newborn outcomes in post-BS pregnancies were collected.

Results
Between 2010 and 2022, 113 women gave birth after BS. This included 17 and 96 patients in Groups 1 and 2. The mean SCTs were 8.0 ± 2.7 and 39.0 ± 24.3 months (p < 0.001), respectively. At BS, the characteristics of age (p = 0.316), weight (p = 0.718), body mass index (BMI) (p = 0.114) and surgical technique used (p = 0.648) were similar. During pregnancy, the mean age of Group 1 women was significantly lower (p = 0.005). With no difference in weight (p = 0.961) or BMI (p = 0.567), the incidence of gestational diabetes mellitus (GDM, p = 0.039) was higher in Group 2. The mean gestational age at delivery (p = 0.206) and incidence rates of preterm (p = 0.645), post-term (p = 1.00) and caesarean deliveries (p = 1.00) in the groups were similar. A significantly higher incidence of delivery induction (p < 0.001 was detected in Group 2. The mean newborn weight in Group 1 was lower (p = 0.038), but the mean birth weight standard deviation (p = 0.883) and incidences of low birth weight (< 2500 g, p = 0.345) and small-for-gestational-age newborns (p = 0.469) were similar. The 1- (p = 0.191) and 5-min (p = 0.174) Apgar points in the groups were similar, and no associations between pregnancy outcomes and surgery technique were detected.

Conclusions
The outcome in pregnancies with an SCT 12 months, postponing pregnancy may not always improve pregnancy outcomes. Therefore, all risks should be weighed when counselling women regarding the optimal time of pregnancy after BS.
Uncertain significance and molecular insights of CPLANE1 variants in prenatal diagnosis of Joubert syndrome: a case report
Authors: Li Si-Xiu , Chen Leiting , Deng Chen , Tang Dongmei , Zhang Jing , Hu Wen-Guang , Hu Yu , Lai Hua , Yang Xiao 
Published: December 2024

Abstract
Background
Prenatal whole exome sequencing (WES) is becoming an increasingly used diagnostic tool for fetuses with structural anomalies. However, the identification of variants of uncertain significance (VUS) in clinically relevant genes can significantly complicate prenatal diagnosis and genetic counseling.

Case presentation
A fetus conceived through in vitro fertilization at the third attempt presented with polydactyly and molar tooth sign at 24 + 6 weeks of gestation. Trio-based WES was performed on both parents and the affected fetus, revealing a pair of compound heterozygous CPLANE1 variants (c.4646 A > T/p.Glu1549Val and c.1233 C > A/p.Tyr411*) potentially associated with Joubert syndrome. According to the ACMG guidelines, one of the biallelic variants was classified as VUS, and the other as pathogenic. However, these variants had no allele frequencies in the general population. The p.Tyr411* variant was classified as deleterious, while the p.Glu1549Val variant was located in highly conserved residues, was predicted to be damaging by in silico tools, and altered hydrogen bonding. Furthermore, CPLANE1 expression was highest in the brain during the embryonic and fetal stages. These findings provide additional support for the association between CPLANE1 variants in this fetus and Joubert syndrome. Thus, the most likely diagnosis was Joubert syndrome, and after careful consideration, the couple decided to terminate the pregnancy.

Conclusion
The expression patterns of CPLANE1 and the molecular effects of the variants may provide further evidence supporting the potential for prenatal diagnosis of Joubert syndrome in the case of biallelic VUS and pathogenic variant. This study suggests that molecular insights may play a role in interpreting VUS in clinically relevant prenatal genes for prenatal diagnosis.
Assessment of recurrent fever among children undergoing tonsillectomy
Authors: Espahbodi Mana , Edwards Kathryn M. , Goudy Steven L. , Penn Edward B. , Manthiram Kalpana 
Published: December 2024

Abstract
Background
Recurrent tonsillitis is a common indication for tonsillectomy in children and has phenotypic overlap with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome. We sought to characterize symptoms associated with PFAPA among children undergoing tonsillectomy.

Methods
Parents/guardians of children undergoing tonsillectomy at Vanderbilt Children’s Hospital over a six-week period were queried regarding symptoms of recurrent fever. Follow-up questionnaires were administered 3 and 12 months after tonsillectomy.

Results
82% (120/147) of patients who underwent tonsillectomy during the study period participated. Provider-documented indications for tonsillectomy were obstructive sleep apnea in 88% and recurrent tonsillitis in 33%. 11% (13/120) reported$$\:\:\ge\:$$6 episodes of stereotypical fever in a one-year period. During febrile episodes among these 13 subjects, 11 had tonsillitis, 5 had cervical adenitis, 3 had aphthous stomatitis, and three reported regular and predictable episode timing. In addition, participants with ≥3 episodes/year of recurrent febrile tonsillitis (N = 33) had a significantly higher prevalence of recurrent aphthous ulcers than those without recurrent tonsillitis (24% vs. 9%, p = 0.04). All participants, including those with recurrent fever, reported fewer febrile tonsillitis episodes one year after tonsillectomy.

Conclusions
In our survey of children undergoing tonsillectomy, a subpopulation had frequent, stereotypical fever episodes with recurrent tonsillitis, aphthous stomatitis, or regular timing like patients with PFAPA. Although we cannot diagnose such patients with PFAPA in this limited retrospective study, pediatricians and otolaryngologists evaluating patients for tonsillectomy should be aware of the clinical signs of PFAPA that may warrant additional evaluation and therapeutic approaches.
Forecast of total health expenditure on China’s ageing population: a system dynamics model
Authors: Luo Shihua , Zhang Junlai , Heffernan Mark 
Published: December 2024

Abstract
Background
China is currently at a turning point as its total population has started to decline, and therefore faces issues related to caring for an ageing population, which will require an increase in Total Health Expenditure (THE). Therefore, the ability to forecast China’s future THE is essential.

Methods
We developed two THE System Dynamics (SD) models using Stella Architect 3.4 to simulate China’s THE from 2000 to 2060. The constant prices THE SD model estimates THE under low, medium, and high Total Fertility Rate (TFR) scenarios. The current prices THE SD model serves as a robust calibration check. In addition, we developed a new total Gross Domestic Production (GDP) forecast model to estimate THE/GDP over the same period.

Results
Our simulation results reveal a significant upward trend in China’s THE from 2000 to 2060. Specifically, under the low TFR scenario, THE is projected to reach approximately $33.4 trillion in 2015 constant USD by 2060. However, with the introduction of efficiency impact factors, THE is expected to fall to around $8.6 trillion by 2060. Additionally, the per capita Health Expenditure is anticipated to rise from $102 in 2000 to roughly $30,800 by 2060, though it could see a decrease to nearly $7,900 with efficiency improvements. Our GDP forecast for 2060 is nearly $87 trillion, with THE to GDP ratio expected to be about 9.7%. In our scenario analysis, as TFR increases, the growing new births and decreased ageing rate are expected to lead to a rise in THE and a decrease in per capita Health Expenditure.

Conclusion
The efficiency of THE utilization needs to be improved. Increasing TFR can help alleviate population decline and ageing to some extent. Enhancing workforce productivity and sustained economic growth is needed to counteract the challenges posed by an ageing population.
Canid alphaherpesvirus 1 infection alters the gene expression and secretome profile of canine adipose-derived mesenchymal stem cells in vitro
Authors: Prišlin Šimac Marina , Naletilić Šimun , Kostanić Vjekoslava , Kunić Valentina , Zorec Tomaž Mark , Poljak Mario , Vlaj Doroteja , Kogoj Rok , Turk Nenad , Brnić Dragan 
Published: December 2024

Abstract
Background
Canine adipose-derived mesenchymal stem cells (cAD-MSCs) demonstrate promising tissue repair and regeneration capabilities. However, the procurement and preservation of these cells or their secreted factors for therapeutic applications pose a risk of viral contamination, and the consequences for cAD-MSCs remain unexplored. Consequently, this research sought to assess the impact of canid alphaherpesvirus 1 (CHV) on the functional attributes of cAD-MSCs, including gene expression profiles and secretome composition.

Methods
To this end, abdominal adipose tissue from 12 healthy dogs was harvested to isolate cAD-MSCs. These samples were tested for CHV contamination before introducing a wild-type CHV strain via serial passages. Following CHV infection, real-time reverse transcription-polymerase chain reaction array and liquid chromatography with tandem mass spectrometry assessments enabled analyses of gene expression and secretome’s proteomic profile, respectively.

Results
This study showed that the initial cAD-MSC populations were devoid of CHV. cAD-MSCs showed susceptibility to infection with wild-type CHV, leading to notable modifications in gene expression and secretome profile. The observed genomic variations in gene expression indicate potential impacts on the stemness, migration, and other functional properties of cAD-MSCs, highlighting the need for further studies to evaluate their functional capacity post-infection. Moreover, gene expression and secretome analyses suggest a shift in stem cell differentiation toward an adipogenic phenotype.

Conclusion
To the best of our knowledge, this is the first study of the effects of virus infection on gene expression and secretome composition in cAD-MSCs. The outcomes of our study underscore the imperative of routine viral screening prior to the therapeutic use of cAD-MSCs. Moreover, these findings provide novel insights into the pathogenic mechanisms of CHV and pave the way for future canine stem cell and virus research.
Agrobacterium-mediated transient transformation of Flaveria bidentis leaves: a novel method to examine the evolution of C4 photosynthesis
Authors: Baros Christopher J. , Beerkens Jeremy , Ludwig Martha 
Published: December 2024

AbstractThe genus Flaveria has been studied extensively as a model for the evolution of C4 photosynthesis. Thus far, molecular analyses in this genus have been limited due to a dearth of genomic information and the lack of a rapid and efficient transformation protocol. Since their development, Agrobacterium-mediated transient transformation protocols have been instrumental in understanding many biological processes in a range of plant species. However, this technique has not been applied to the genus Flaveria. Here, an efficient protocol for the Agrobacterium-mediated transient transformation of the leaves of the C4 species Flaveria bidentis is presented. This technique has the distinct advantages of rapid turnaround, the ability to co-transform with multiple constructs, and the capacity to assay coding and non-coding regions of Flaveria genomes in a homologous context. To illustrate the utility of this protocol, the quantitative transcriptional regulation of phosphoenolpyruvate carboxylase, the primary carboxylase of C4 plants, was investigated. A 24 bp region in the ppcA1 proximal promoter was found to elicit high levels of reporter gene expression. The Agrobacterium-mediated transient transformation of F. bidentis leaves will accelerate the understanding of the biology and evolution of C4 photosynthesis in the genus Flaveria as well as in other C4 lineages.
Two-year follow-up after drug desensitization in mucopolysaccharidosis
Authors: Spataro Federico , Ria Roberto , Chaoul Nada , Solimando Antonio Giovanni , Desantis Vanessa , Vacca Angelo , Di Bona Danilo , Girolamo Attilio Di , Macchia Luigi 
Published: December 2024

Abstract
Background
Mucopolysaccharidosis (MPS) type 1 S and type 2 are rare lysosomal storage disorders characterized by impaired enzyme production, resulting in glycosaminoglycans accumulation within lysosomes. Enzyme Replacement Therapy (ERT) with laronidase and idursulfase are first line treatments, respectively. However, infusion-related hypersensitivity reactions (HR) may lead to ERT discontinuation. Thus, desensitization can be performed to restore ERT.

Methods
We report on a two-year follow-up after a combined desensitization approach in two MPS patients experiencing HR to ERT. This approach consists of intravenous rapid desensitization combined with the subcutaneous allergen immunotherapy-like desensitization with the culprit recombinant enzyme.

Results
The first patient, suffering from MPS type I, underwent to the combined desensitization approach, and subsequently tolerated weekly standard laronidase infusions for 13 months when HR occurred again. Then, a monthly omalizumab (anti-IgE monoclonal antibody) administration was implemented allowing the patient to restore ERT. The second patient, diagnosed with MPS type 2, was subjected to a similar combined desensitization strategy with idursulfase, and achieved a total desensitization after one year, confirmed by negative skin tests. Thus, he continued standard ERT infusions without HR occurrence.

Conclusion
The combined desensitization approach proved effective in conferring immunotolerance for at least one year in both MPS patients, also demonstrated by the negative skin tests in one patient. However, when immunotolerance to ERT is lost, omalizumab administration can be a valid option in restoring ERT.
Conservation of the dehiscence zone gene regulatory network in dicots and the role of the SEEDSTICK ortholog of California poppy (Eschscholzia californica) in fruit development
Authors: Lotz Dominik , Rössner Le Han , Ehlers Katrin , Kong Doudou , Rössner Clemens , Rupp Oliver , Becker Annette 
Published: December 2024

Abstract
Background
Fruits, with their diverse shapes, colors, and flavors, represent a fascinating aspect of plant evolution and have played a significant role in human history and nutrition. Understanding the origins and evolutionary pathways of fruits offers valuable insights into plant diversity, ecological relationships, and the development of agricultural systems. Arabidopsis thaliana (Brassicaceae, core eudicot) and Eschscholzia californica (California poppy, Papaveraceae, sister group to core eudicots) both develop dry dehiscent fruits, with two valves separating explosively from the replum-like region upon maturation. This led to the hypothesis, that homologous gene regulatory networks direct fruit development and dehiscence in both species.

Results
Transcriptome analysis of separately collected valve and replum-like tissue of California poppy yielded the SEEDSTICK (STK) ortholog as candidate for dehiscence zone regulation. Expression analysis of STK orthologs from dry dehiscing fruits of legumes (Vicia faba, Glycine max and Pisum sativum) shows their involvement in fruit development. Functional analysis using Virus-Induced Gene Silencing (VIGS) showed premature rupture of fruits and clarified the roles of EscaSTK: an evolutionary conserved role in seed filling and seed coat development, and a novel role in restricting cell divisions in the inner cell layer of the valve.

Conclusion
Our analysis shows that the gene regulatory network described in Arabidopsis is significantly different in other dicots, even if their fruits form a dehiscence zone at the valve margins. The ortholog of STK, known to be involved in ovule development and seed abscission in Arabidopsis, was recruited to a network regulating fruit wall proliferation in California poppy. There, EscaSTK allows fruit maturation without premature capsule rupture, highlighting the importance of proper endocarp development for successful seed dispersal.
Discrimination of benign, atypical, and malignant peripheral nerve sheath tumours in neurofibromatosis type 1 – intraindividual comparison of positron emission computed tomography and diffusion-weighted magnetic resonance imaging
Authors: Ristow Inka , Apostolova Ivayla , Kaul Michael G. , Stark Maria , Zapf Antonia , Schmalhofer Marie-Lena , Mautner Victor F. , Farschtschi Said , Adam Gerhard , Bannas Peter , Salamon Johannes , Well Lennart 
Published: December 2024

Abstract
Background
To intraindividually compare the diagnostic performance of positron emission computed tomography (F-18-FDG-PET/CT) and diffusion-weighted magnetic resonance imaging (DW-MRI) in a non-inferiority design for the discrimination of peripheral nerve sheath tumours as benign (BPNST), atypical (ANF), or malignant (MPNST) in patients with neurofibromatosis type 1 (NF1).

Results
In this prospective single-centre study, thirty-four NF1 patients (18 male; 30 ± 11 years) underwent F-18-FDG-PET/CT and multi-b-value DW-MRI (11 b-values 0 – 800 s/mm²) at 3T. Sixty-six lesions corresponding to 39 BPNST, 11 ANF, and 16 MPNST were evaluated. Two radiologists independently assessed the maximum standardized uptake value (SUVmax) and mean and minimum apparent diffusion coefficient (ADCmean/min) as well as the ADC in areas of lowest signal intensity in each lesion (ADCdark). The AUCs of DW-MRI and F-18-FDG-PET/CT were compared to determine whether the ADC is non-inferior to SUVmax (non-inferiority margin equal to -10%). Follow-up of ≥ 24 months (BPNST) or histopathological evaluation (MPNST + ANF) served as diagnostic reference standard. Both SUVmax and ADC parameters demonstrated good diagnostic accuracy (AUCSUVmax 94.0%; AUCADCmean/min/dark 91.6% / 90.1% / 92.5%). However, non-inferiority could not be demonstrated for any of the three ADC parameters (lower limits of the confidence intervals of the difference between the AUC of ADCmean/min/dark and SUVmax -12.9% / -14.5% / -11.6%). Inter-rater reliability was excellent for both imaging techniques (Krippendorff’s alpha all > 0.94).

Conclusions
Both PET/CT-derived SUVmax and MRI-derived ADC allow sensitive and non-invasive differentiation of benign and (pre)-malignant peripheral nerve sheath tumours. Nevertheless, DW-MRI cannot be considered as non-inferior to F-18-FDG-PET/CT in this prospective single-centre study.