bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiographic Soft Tissue Thickness Is Not a Risk Factor for Infection after Primary Total Ankle Arthroplasty
Authors: Anastasio Albert T. , Wu Kevin , Kutzer Katherine , Krez Alexandra , DeOrio James K. , Easley Mark E. , Nunley James A. , Adams Samuel B.
Published: December 2024

Category:

Ankle; Ankle Arthritis

Introduction/Purpose:

Total ankle arthroplasty (TAA) is a commonly performed surgical procedure to address end-stage arthritis. Previous studies have suggested that the radiographic soft tissue thickness may be a predictor of complications including periprosthetic joint infection (PJI) after orthopedic surgery. However, there has been limited studies exploring the use of radiographic soft tissue thickness in TAA. The purpose of this study was to evaluate the predictive capabilities of radiographic soft-tissue thickness for PJI following TAA.

Methods:

A retrospective analysis of 323 patients at a single institution who underwent primary TAA from 2003 to 2019 was conducted. Patient characteristics, including age, sex, body mass index (BMI), and comorbidities such as diabetes, smoking status, and etiology of ankle injury were recorded. Preoperative radiographic measurements, including the Tibial-Tissue and Talus-Tissue distances were recorded. Other perioperative information included prosthesis type, tourniquet time, and time to last follow-up. Logistic regression was utilized to examine the relationship between these factors and the occurrence of PJI.

Results:

Of the 323 patients, there were 6 patients (1.86%) who developed a PJI. The logistic regression analysis revealed that neither Tibial-Tissue (Odds Ratio: 0.975 [0.947 - 1.004]; p = 0.09) nor Talus-Tissue thickness (Odds Ratio: 0.976 [0.940 - 1.012]; p = 0.18) were significant predictors of PJI. Although not statistically significant, the infected cohort had smaller average Tibial-Tissue (2.20 vs. 2.53 cm; p=0.05) and Talus-Tissue thickness (2.19 vs. 2.44 cm; p=0.36) compared to the non-infected cohort.

Conclusion:

Despite an association between radiographic soft tissue thickness and infection in other orthopedic surgeries, measurements such as Tibial-Tissue length and Talus-Tissue length were not significant predictors of PJI following primary TAA. These findings underscore the necessity for additional research to identify modifiable risk factors aimed at reducing PJI rates and enhancing patient outcomes.
Pharmaceutical Industry Payments to Patient Organizations in Poland: Analysis of the Patterns, Evolution, and Structure of Connections
Authors: Makowska Marta , Mulinari Shai , Ozieranski Piotr
Published: December 2024

Drug company funding can create conflicts of interest that compromise the integrity of patient organizations, a problem studied primarily in Western Europe and North America. To address this research gap, we conducted a case study in Poland, a Central European country. Between 2012 and 2020, 33 companies reported payments worth €13 729 644 to 273 patient organizations in Poland. The funding was highly concentrated, with the top ten recipients amassing 46.2 percent of the total amount. Cancer patient organizations were the primary recipients, receiving 37.5 percent. The funding focused on patient organizations’ educational activities, constituting 40.4 percent of the total. For the ten companies reporting payments consistently from 2012 to 2020, we detected an increase in both the value of individual payments and the overall value of the funding. Additionally, some patient organizations formed exclusive, or nearly exclusive, ties with single companies. Overall, our study reveals important similarities between Poland and Western countries in the reported distribution of drug company payments to patient organizations. It also highlights priority areas for further research, including the evolution and structure of the financial connections.
Invasive Hemodynamic Assessment Is Mandatory to Confirm Bioprosthetic Valve Dysfunction and Failure Following TAVR
Authors: Khalili Houman , Abbas Amr E.
Published: December 2024

Echocardiography is commonly used for clinical evaluation of bioprosthetic valves. However, the clinical significance of an isolated high gradient detected by echocardiography is unclear. This uncertainty arises from discrepancies between echocardiographic and invasive gradient measurements in normally functioning prosthetic valves, that is attributed to limitations of the Bernoulli principle among other factors. Furthermore, the relationship between echocardiographic gradient and clinical outcomes is complex and nonlinear. To avoid unnecessary interventions, it is crucial to confirm an unfavorable gradient detected by echocardiography through invasive measurements, particularly when valve thrombosis is absent.
Real-world treatment patterns and health care resource use for patients with myelofibrosis: results from the METER study
Authors: Gupta Vikas , Tomuleasa Ciprian , Barranco Lampón Gilberto Israel , Hou Hsin-An , Helbig Grzegorz , Vachhani Pankit , Symeonidis Argiris , Haznedaroglu Ibrahim , Galvez Kenny , Tatsch Fernando , Chopra Avijeet S. , Zhang Meng , Vizkelety Tamas , Murray Bryan , Ross David M.
Published: December 2024

Myelofibrosis (MF), a myeloproliferative neoplasm, was most commonly treated with hydroxyurea (HU) before approval of ruxolitinib (RUX), now the standard of care. Factors that influence real-world MF treatment patterns are not well understood. The METER study was a multi-country, retrospective chart review of MF treatment patterns, treatment effectiveness, and health care resource utilization. Of 997 eligible patients, 65.9% had primary MF, and 11.7% were transfusion dependent. Median time from diagnosis to the start of initial treatment (index date) was 29 days (interquartile range [IQR], 1-140). RUX was the most common first-line (1L) therapy (49.0%), followed by HU (40.2%); 48.5% of patients remained on 1L therapy through week 156. Seventy-seven patients underwent allogeneic stem cell transplantation; transplantation was uncommon at 1L, increasing from 2.2% at week 24 to 11.0% at week 156 in patients ≤70 years of age. Median overall survival was 79.1 months (95% confidence interval [95% CI], 70.8 to not estimable [NE]) in all patients, 142.3 months (95% CI, 74.1 to NE) for non-RUX patients, 77.6 months (95% CI, 64.2-85.9) for patients on RUX 1L therapy, and 72.6 months (95% CI, 62.0 to NE) for RUX 2L+ patients. Of patients who experienced ≥1 corresponding event, the median hospital length of stay (LoS; n = 520), intensive care unit LoS (n = 71), and number of transfusions (n = 375) were 16 days (IQR, 7-37), 5 days (IQR, 2-13), and 12 (IQR, 4-26), respectively. Despite improvements, there were numerous hospitalization and transfusion events among these patients in routine practice. This trial was registered at www.ClinicalTrials.gov as #NCT05444972.
The interplay of factors in metabolic syndrome: understanding its roots and complexity
Authors: Islam Md. Sharifull , Wei Ping , Suzauddula Md , Nime Ishatur , Feroz Farahnaaz , Acharjee Mrityunjoy , Pan Fan
Published: December 2024

Metabolic syndrome (MetS) is an indicator and diverse endocrine syndrome that combines different metabolic defects with clinical, physiological, biochemical, and metabolic factors. Obesity, visceral adiposity and abdominal obesity, dyslipidemia, insulin resistance (IR), elevated blood pressure, endothelial dysfunction, and acute or chronic inflammation are the risk factors associated with MetS. Abdominal obesity, a hallmark of MetS, highlights dysfunctional fat tissue and increased risk for cardiovascular disease and diabetes. Insulin, a vital peptide hormone, regulates glucose metabolism throughout the body. When cells become resistant to insulin’s effects, it disrupts various molecular pathways, leading to IR. This condition is linked to a range of disorders, including obesity, diabetes, fatty liver disease, cardiovascular disease, and polycystic ovary syndrome. Atherogenic dyslipidemia is characterized by three key factors: high levels of small, low-dense lipoprotein (LDL) particles and triglycerides, alongside low levels of high-density lipoprotein (HDL), the “good” cholesterol. Such a combination is a major player in MetS, where IR is a driving force. Atherogenic dyslipidemia contributes significantly to the development of atherosclerosis, which can lead to cardiovascular disease. On top of that, genetic alteration and lifestyle factors such as diet and exercise influence the complexity and progression of MetS. To enhance our understanding and consciousness, it is essential to understand the fundamental pathogenesis of MetS. This review highlights current advancements in MetS research including the involvement of gut microbiome, epigenetic regulation, and metabolomic profiling for early detection of Mets. In addition, this review emphasized the epidemiology and fundamental pathogenesis of MetS, various risk factors, and their preventive measures. The goal of this effort is to deepen understanding of MetS and encourage further research to develop effective strategies for preventing and managing complex metabolic diseases.
Investigating the inflammatory mechanism of notoginsenoside R1 in Diabetic nephropathy via ITGB8 based on network pharmacology and experimental validation
Authors: Li ChangYan , Geng Chen , Wang JiangMing , Shi Luyao , Ma JingYuan , Liang Zhang , Fan WenXing
Published: December 2024

Background

Diabetes often causes diabetic nephropathy (DN), a serious long-term complication. It is characterized by chronic proteinuria, hypertension, and kidney function decline, can progress to end-stage renal disease, lowering patients’ quality of life and lifespan. Inflammation and apoptosis are key to DN development. Network pharmacology, clinical correlation, and basic experimental validation to find out how NGR1 might work to reduce inflammation in DN treatment. The study aims to improve DN treatment with new findings.

Methods

To determine how NGR1 treats DN, this study used network pharmacology, clinical correlation, and basic experimental validation. Three methods were used to predict NGR1 drug targets: ChEMBL, SuperPred, and Swiss Target Prediction. Drug targets are linked to diseases by molecular docking. A clinical correlation analysis using the Nephroseq Classic (V4) database looked at the strong link between medication targets and the development, progression, and renal function of DN. Additional research showed that NGR1 reduces high blood sugar-induced podocyte inflammation.

Results

The integrin subunit beta 8 (ITGB8) protein is a potential NGR1 therapeutic target for DN. It may be linked to inflammatory proteins like caspase 3 and IL-18. Validation of the molecular docking showed that SER-407, ALA-22, Ala-343, and TYR-406 form hydrogen bonds with NGR1 and ITGB8. These interactions represent pharmacodynamic targets. Clinical correlation showed that DN patients had significantly lower ITGB8 expression levels than healthy individuals. Between 50 and 80 years old, DN patients’ ITGB8 expression levels decreased. ITGB8 expression was lowest in renal function conditions, with eGFR values of 15–29 ml/min/1.73 m2. In the db/db mouse model, downregulation of ITGB8 expression in renal tissue was associated with renal inflammatory damage. The hyperglycemic group had significantly lower levels of nephrin and caspase-3 protein, but higher levels of cleaved caspase-1 protein. Giving NGR1 in different amounts (1, 3, 10, and 30 µM) greatly decreased the expression of caspase3, stopped the expression of cleaved caspase1, and lowered the damage caused by NLRP3 in podocytes.

Conclusion

We identified several NGR1 pharmacological targets and found that the ITGB8 protein is a key drug target linked to inflammation and DN. ITGB8 is critical for DN development and can help to reduce high blood sugar-induced podocyte inflammation.
Liner Damage Analysis for Hydrogen Storage Vessels Subjected to Local Compressive Loads Using the Submodeling Method
Authors: Liu Wen , Zhang Lele , Chen Geng , Zhu Yu , Ruan Baofeng
Published: December 2024

When a hydrogen storage vessel is subjected to a local impact load, damage may occur in the liner and result in hydrogen leakage and other catastrophic consequences. When predicting liner damage of a hydrogen storage vessel using the finite element method (FEM), although large element size is required to achieve a desired computational efficiency, it oftentimes causes inaccuracy in the damage model. To remedy this problem, in this study a novel approach which calculates the material damage based on the GISSMO (Generalized Incremental Stress State dependent damage Model) damage model and employs a submodeling strategy is proposed. According to this approach, the global model is discretized to large elements to increase the efficiency, while the submodel is meshed to much smaller elements to accurately reflect the material damage. Employing the established approach and material parameters calibrated from a large set of notched aluminum alloy 5083 specimens, the liner damage of a type III hydrogen storage vessel subjected to a local compressive load was simulated. This way, the study reveals how the characteristics of the stress and material damage interact with each other. In addition, the study also demonstrates that the proposed approach can be used as a viable means to evaluate the damage within hydrogen storage vessels.
WNT4 promotes the symmetric fission of crypt in radiation-induced intestinal epithelial regeneration
Authors: Cheng Jingyang , Wu Haiyong , Cui Yanmei
Published: December 2024

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

The 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

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

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

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

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

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

The 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

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

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

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.
Immunophenotypic analysis on circulating T cells for early diagnosis of lung cancer
Authors: Lee Sung-Woo , Kim Young Ju , Rho Kyung Na , Jeong Saei , Noh Jeong Eun , Kim Hee-Ok , Cho Hyun-Ju , Yun Ju Sik , Oh In-Jae , Cho Jae-Ho
Published: December 2024

The immune system continuously interacts with tumors, possibly leading to systemic alterations in circulating immune cells. However, the potential of these cancer-associated changes for diagnostic purposes remains poorly explored. To investigate this, we conducted a comprehensive flow cytometric analysis of 452 peripheral blood mononuclear cell (PBMC) samples from 206 non-small-cell lung cancer (NSCLC) patients, 100 small-cell lung cancer (SCLC) patients, 94 healthy individuals, and 52 benign lung disease (BLD) patients. We focused specifically on circulating T cells, given their close interaction with tumors, and initially assessed 93 T-cell features from the flow cytometric analysis. Using a feature selection protocol, we identified five T-cell features in peripheral blood with strong diagnostic relevance. Notably, while individual alterations in these features lacked cancer specificity, simultaneous alterations were uniquely indicative of lung cancer. To comprehensively analyze these features, we developed a scoring model, “IMmunoPhenotypic Analysis for Cancer deTection (IMPACT).” Comprehensive analysis using the five features (IMPACT-5) demonstrated high cancer specificity and biomarker efficacy, as evidenced by the high area under the receiver operating characteristic curve values for lung cancer patients (0.9187, 0.9277, and 0.9363 for stage I NSCLC, stage IV NSCLC, and SCLC patients, respectively), in stark contrast to BLD patients (0.5212). These findings suggest that comprehensive analysis of cancer-associated changes in circulating T cells can effectively detect lung cancer from its early stages, proposing immunophenotypic analysis of circulating T cells as an innovative liquid biopsy-based diagnostic biomarker.
Evolution characteristic of soil water in loess slopes with different slope angles
Authors: Bao Han , Lann Tongsan , Ao Xinlin , Yang Liya , Lan Hengxing , Peng Jianbing
Published: December 2024

Background

In the Loess Plateau region, significant engineering activities have led to many exposed loess slopes. These slopes have undergone a series of shallow failures under rainfall, significantly affecting their stability. Vegetation can somewhat restore the ecological damage to the slope surfaces and enhance their stability. Thus, studying the spatiotemporal evolution of soil moisture migration under vegetation protection on loess slopes is crucial.

Methods

Employing experimental designs with slope gradients of 45° and 60°, this investigation is structured around a trio of core objectives: to delineate the processes of rainfall infiltration and its redistribution within the slope, to chart the evolution of soil water within the loess soil matrix, and to discern the impacts of slope inclination on soil water dynamics. Critical to this study are the monitoring of volumetric moisture content, matric suction, and the external variables of rainfall and temperature, alongside an analysis of soil water potential and moisture movement as observed in laboratory setups and simulated through Hydrus-2D.

Results

The study revealed that slope angle significantly affects soil moisture infiltration and redistribution. The steeper slope (60°) exhibited more pronounced fluctuations in soil water potential, particularly during the rainy season, reflecting the dynamic nature of water movement. This slope also demonstrated sharper transitions in soil moisture during drying periods, indicating a greater sensitivity to weather changes. Water movement parallel to the slope surface was faster on steeper slopes, especially under drying conditions, with more pronounced lateral downslope flow at the surface layer. In contrast, the gentler slope (45°) showed more consistent moisture retention during wet periods, with slower and more uniform soil moisture movement, leading to a steadier moisture gradient and prolonged upslope movement. Vegetation plays a crucial role in modulating soil moisture dynamics, with grass growth being more effective on the steeper 60° slope. The extensive root network on this slope enhanced water retention, increased soil permeability, and reduced erosion. During the drying phase, deeper root systems significantly reduced volumetric water content at shallower depths, promoting higher moisture content in the middle sections of the slope.
Anesthetic management using desflurane and nitrous oxide in a child with non-ketotic hyperglycinemia: a case report
Authors: Mashima Akifumi , Furutani Kenta , Baba Hiroshi
Published: December 2024

Background

Non-ketotic hyperglycinemia (NKH) is a rare autosomal recessive disorder caused by defects in the glycine cleavage system, leading to elevated glycine levels in the central nervous system. NKH manifests in various forms, with the neonatal type being the most severe and often associated with high mortality and significant neurological impairment. This case report highlights the successful uses of desflurane and nitrous oxide for anesthetic management in a patient with NKH.

Case presentation

A 6-year-old girl with severe NKH, who had a history of delayed emergence from sevoflurane anesthesia, underwent tracheostomy for recurrent upper airway obstruction and severe obstructive sleep apnea. To address the previous issues with sevoflurane, general anesthesia was induced with propofol and fentanyl and maintained with 4% desflurane and 60% nitrous oxide. The electroencephalogram (EEG) showed near-complete suppression upon induction, which gradually resolved. Following cessation of desflurane and nitrous oxide, the patient exhibited early recovery, with eyes opening 3 min later and spontaneous breathing restored 19 min later. The patient experienced no postoperative complications and was discharged on the 14th postoperative day.

Conclusion

This case suggests that desflurane, with its favorable pharmacological profile, may offer a superior alternative to sevoflurane for anesthetic management in NKH patients, particularly those with a history of delayed emergence. The observed EEG suppression may indicate heightened sensitivity to anesthetics in NKH, highlighting the need for tailored anesthetic strategies in this population.
Immune deficiency phenotypes of Il2rg, Rag2 or Il2rg/Rag2 double knockout rats; establishment of human leukemia xenograft models
Authors: Kim Joo-Il , Lim Hyun-Jin , Kwon Euna , Mashimo Tomoji , Kang Byeong-Cheol
Published: December 2024

Background

Genetically immunodeficient mice lacking Il2rg and Rag2 genes have been widely utilized in the field of biomedical research. However, immunodeficient rats, which offer the advantage of larger size, have not been as extensively used to date. Recently, Severe Combined Immunodeficiency (SCID) rats were generated using CRISPR/Cas9 system, targeting Il2rg and Rag2 in National BioResource Project in Japan. We imported and investigated more detailed phenotypes of wild-type (WT) Il2rg knockout (KO), Rag2 KO and Il2rg/Rag2 KO rats for 20 weeks.

Results

During experiments, Il2rg KO, Rag2 KO and Il2rg/Rag2 KO rats showed decreased white blood cells and systemic lymphopenia, with reduced CD4+, CD8+ T cells and CD161+ NK cells. Additionally, all KO strains exhibited reduced relative spleen weights, hypoplasia of the germinal center in the white pulp, and atrophy with the disappearance of the boundary between the cortex and medulla in the thymus, compared to WT rats. Furthermore, we established human acute lymphoblastic leukemia xenograft rat model by intravenously injecting 5.0 × 106 cells/kg of NALM6 cells into Il2rg/Rag2 KO rats.

Conclusions

These findings indicate that Il2rg KO, Rag2 KO, and Il2rg/Rag2 KO rats exhibited SCID phenotypes, suggesting their potential application as immunodeficient animal models for tumor xenograft studies.
The relationship between dimensions of corporate social responsibility and consumer’s buying intentions in a cross-cultural context
Authors: Subhani Inayat ul Haq , Fan Jun , Asdullah Muhammad Ashar , Watto Waqas Ahmad , Nigar Fareeha
Published: December 2024

This study investigates the cross-cultural relationships of corporate social responsibility (CSR) factors, culture dimensions, and consumer’s buying intentions in China and Pakistan. Moreover, this study also reveals the moderating effect of national culture values on these relationships. Data from 239 respondents from each sample group were collected through a questionnaire survey. Structural equation modeling was used to test the hypothesis. The results from the Chinese sample group showed that ethical CSR and philanthropic CSR has a significant impact on buying intention, while economic CSR and legal CSR have an insignificant impact on buying intention. Moreover, data from Pakistan found that legal, ethical and philanthropic CSR have a significant impact, while economic CSR has an insignificant impact on buying intentions of consumers. Significant moderation impact of national cultural values is observed on the relationship of economic CSR and buying intention, however, the insignificant impact of national culture values proved on the relationship of legal, ethical, and philanthropic CSR and buying intention. This study provides substantial insights for the industry that strong improvement and appropriate communication of philanthropic and ethical CSR stimulates the consumers’ motivation to alter their buying intentions and help them to retain loyalty.
Retraction Note: Current design of rectangular steel silos: limitations and improvement
Authors: Abdelbarr Mohamed H. , Ramadan Osman M. O. , Hilal AlHussein , Sanad A. M. , Abdalla Hany A.
Published: December 2024

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s44147-024-00401-1.
Trinucleotide repeat expansion and RNA dysregulation in fragile X syndrome: emerging therapeutic approaches
Authors: Jung Suna , Richter Joel D.
Published: December 2024

Fragile X syndrome (FXS) is characterized by intellectual impairment caused by CGG repeat expansion in theFMR1gene. When repeats exceed 200, they induce DNA methylation of the promoter and the repeat region, resulting in transcriptional silencing of theFMR1gene and the subsequent loss of FMRP protein. In the past decade or so, research has focused on the role of FMRP as an RNA-binding protein involved in translation inhibition in the brain in FXS model mice, particularly by slowing or stalling ribosome translocation on mRNA. More recent advances have shown that FMRP has a profound role in RNA splicing, at least in some cases by modulating the translation of splicing factor mRNAs. In a surprise, the humanFMR1gene is transcribed in most cases even with a full CGG expansion. However, much of theFMR1that is produced is misspliced, which can be corrected by splice-switching antisense oligonucleotide (ASO) administration. Other recent findings suggest that inhibition of multiple kinases can demethylate theFMR1gene and induce the formation of an R-loop in the CGG repeat region, leading to contraction of the repeat and FMRP restoration. These insights are paving the way for possible future therapeutic approaches for this disorder. We highlight the importance of FMRP restoration by ASO-mediated splice switching or CGG repeat modulation as key advances that may lead to successful treatments for FXS.