bluuebunny/crossref_metadata_2025 huggingface dataset:
Recombinant production of SAG1 fused with xylanase in Pichia pastoris induced higher protective immunity against Eimeria tenella infection in chicken
Authors: Liu Chen , Wei HanBing , Liang Ruiying , Wang Yuan , Su Xiaoyun , Tu Tao , Luo Huiying , Yao Bin , Ding Jiabo , Tang Xinming , Huang Huoqing , Zhang Honglian
Published: March 2024

Chicken coccidiosis is an intestinal disease caused by the parasite Eimeria, which severely damages the growth of chickens and causes significant economic losses in the poultry industry. Improvement of the immune protective effect of antigens to develop high efficiency subunit vaccines is one of the hotspots in coccidiosis research. Sporozoite‐specific surface antigen 1 (SAG1) of Eimeria tenella (E. tenella) is a well‐known protective antigen and is one of the main target antigens for the development of subunit, DNA and vector vaccines. However, the production and immunoprotective effects of SAG1 need to be further improved. Here, we report that both SAG1 from E. tenella and its fusion protein with the xylanase XynCDBFV‐SAG1 are recombinant expressed and produced in Pichia pastoris (P. pastoris). The substantial expression quantity of fusion protein XynCDBFV‐SAG1 is achieved through fermentation in a 15‐L bioreactor, reaching up to about 2 g/L. Moreover, chickens immunized with the fusion protein induced higher protective immunity as evidenced by a significant reduction in the shedding of oocysts after E. tenella challenge infection compared with immunized with recombinant SAG1. Our results indicate that the xylanase enhances the immunogenicity of subunit antigens and has the potential for developing novel molecular adjuvants. The high expression level of fusion protein XynCDBFV‐SAG1 in P. pastoris holds promise for the development of effective recombinant anti‐coccidial subunit vaccine.
Non‐small cell lung carcinoma with focal coexpression of thyroid transcription factor‐1 and Δ Np63/p40: A case report
Authors: Terada Kazuhiro , Menju Toshi , Date Horoshi , Haga Hironori , Yoshizawa Akihiko
Published: March 2024

Most lung carcinomas are subtyped by their morphologies; however, immunohistochemistry is usually performed when it is difficult to determine. The most reliable antibodies for distinguishing lung adenocarcinoma from squamous cell carcinoma are thyroid transcription factor‐1 (TTF‐1) and p40 (ΔNp63). In general, these markers are mutually exclusive in their expression of lung primary carcinoma; however, a few cases of non‐small cell lung carcinoma (NSCLC) with coexpression of both markers have been reported. Examining a tissue microarray of 229 squamous cell carcinomas and 346 adenocarcinomas, we found one case of NSCLC with coexpression of TTF‐1 and p40. Herein, we present a 71‐year‐old man, who had a mass lesion in the left lung apex. A transbronchial lung biopsy was performed, revealing NSCLC. He underwent left upper segmentectomy and lymph node dissection. Macroscopically, the mass showed a white‐to‐tan solid tumor on the cut surface. Microscopically, the tumor was composed of polygonal tumor cells which had round and vesicular nuclei with prominent nucleoli. They had an abundant amount of cytoplasm, which was slightly eosinophilic or amphophilic. Multinucleated cells with atypical nuclear features were observed to be scattered in some areas. Multifocal necrosis and hemorrhage were also noted. Distinct squamous features and obvious glandular features were absent. Immunohistochemically, the most tumor cells were coexpressed positive for both TTF‐1 and p40. In our study, NSCLC with TTF‐1 and p40 coexpression is rare; therefore, it is necessary to obtain further data and examine similar cases to establish more precise definitions and clinicopathological features.
Dermal stiffness governs the topography of the epidermis and the underlying basement membrane in young and old human skin
Authors: Roig‐Rosello Eva , Dayan Guila , Bovio Simone , Manissier Patricia , Errazuriz Elisabeth , Rousselle Patricia
Published: March 2024

The epidermis is a stratified epithelium that forms the outer layer of the skin. It is composed primarily of keratinocytes and is constantly renewed by the proliferation of stem cells and their progeny that undergo terminal differentiation as they leave the basal layer and migrate to the skin surface. Basal keratinocytes rest on a basement membrane composed of an extracellular matrix that controls their fate via integrin‐mediated focal adhesions and hemidesmosomes which are critical elements of the epidermal barrier and promote its regenerative capabilities. The distribution of basal cells with optimal activity provides the basement membrane with its characteristic undulating shape; this configuration disappears with age, leading to epidermal weakness. In this study, we present an in‐depth imaging analysis of basal keratinocyte anchorage in samples of human skin from participants across the age spectrum. Our findings reveal that skin aging is associated with the depletion of hemidesmosomes that provide crucial support for stem cell maintenance; their depletion correlates with the loss of the characteristic basement membrane structure. Atomic force microscopy studies of skin and in vitro experiments revealed that the increase in tissue stiffness observed with aging triggers mechanical signals that alter the basement membrane structure and reduce the extent of basal keratinocyte anchorage, forcing them to differentiate. Genomic analysis revealed that epidermal aging was associated with mechanical induction of the transcription factor Krüppel‐like factor 4. The altered mechanical properties of tissue being a new hallmark of aging, our work opens new avenues for the development of skin rejuvenation strategies.
High burden of clonal mast cell disorders and hereditary α‐tryptasemia in patients who need Hymenoptera venom immunotherapy
Authors: Korošec Peter , Sturm Gunter J. , Lyons Jonathan J. , Marolt Tinkara Pirc , Svetina Manca , Košnik Mitja , Zidarn Mihaela , Kačar Mark , Frelih Nina , Lalek Nika , Luzar Ajda Demšar , Zver Samo , Škerget Matevž , Czarnobilska Ewa , Dyga Wojciech , Grle Sanja Popović , Samarzija Miroslav , Arzt‐Gradwohl Lisa , Čerpes Urban , Porebski Grzegorz , Pevec Branko , Schadelbauer Eva , Kopač Peter , Šelb Julij , Rijavec Matija
Published: March 2024

Background

In patients who require venom immunotherapy (VIT), there is a need to identify underlying mast cell (MC) disorders since these may affect the risk and severity of future sting reactions and the long‐term effectiveness of VIT.

Methods

1319 individuals with Hymenoptera venom allergy (HVA) who needed VIT from referral centers in Slovenia, Austria, Croatia, and Poland underwent examination for KIT p.D816V in peripheral blood leukocytes (PBL) using a highly sensitive PCR test and tryptase genotyping by digital droplet PCR. We also included 183 control individuals with large local reactions (LLRs) to Hymenoptera stings and with asymptomatic sensitization to Hymenoptera venoms.

Results

285 of 1319 individuals recommended for VIT (21.6%) were positive for KIT p.D816V in PBL, preferably those who present with severe reaction (33.9% [n = 207 of 610] with Ring‐Messmer grade 3–4 vs. 11% [n = 78 of 709] with Grade 1–2; p < .0001), whereas only 1.3% (n = 2 of 152) of controls with LLR and none with asymptomatic sensitization (n = 31) had KIT p.D816V. KIT p.D816V allelic burden was higher in those with severe reaction (median 0.018% [n = 207] in Grade 3–4 vs. 0.001% [n = 78] in Grade 1–2; p < .0001), and the majority had normal baseline serum tryptase levels (69% [n = 196 of 285]). All KIT p.D816V‐positive individuals (n = 41) who underwent bone marrow (BM) biopsy were found to have underlying clonal diseases, principally BM mastocytosis. HαT was also associated with severe HVA and symptoms (p < .01), and remarkably, 31.0% (n = 31 of 100) were found to have concomitant KIT p.D816V. Concomitant HαT and KIT p.D816V showed an additive effect, and having both was associated with the highest risk for severe HVA, even higher than having either HαT or KIT p.D816V alone (OR = 3.8; p < .01).

Conclusions

By employing prospective universal tryptase genotyping and examination for KIT p.D816V in PBL in large HVA populations, we have demonstrated a high burden of clonal MC disorders and HαT in patients who require VIT.
RNA‐sequencing of paired tape‐strips and skin biopsies in atopic dermatitis reveals key differences
Authors: Fritz Blaine , Halling Anne‐Sofie , Cort Isabel Díaz‐Pinés , Christensen Maria Oberländer , Rønnstad Amalie Thorsti Møller , Olesen Caroline Meyer , Knudgaard Mette Hjorslev , Zachariae Claus , Heegaard Steffen , Thyssen Jacob P. , Bjarnsholt Thomas
Published: March 2024

Background

Skin tape‐strips and biopsies are widely used methods for investigating the skin in atopic dermatitis (AD). Biopsies are more commonly used but can cause scarring and pain, whereas tape‐strips are noninvasive but sample less tissue. The study evaluated the performance of skin tape‐strips and biopsies for studying AD.

Methods

Whole‐transcriptome RNA‐sequencing was performed on paired tape‐strips and biopsies collected from lesional and non‐lesional skin from AD patients (n = 7) and non‐AD controls (n = 5). RNA yield, mapping efficiency, and differentially expressed genes (DEGs) for the two methods (tape‐strip/biopsy) and presence of AD (AD/non‐AD) were compared.

Results

Tape‐strips demonstrated a lower RNA yield (22 vs. 4596 ng) and mapping efficiency to known genes (28% vs. 93%) than biopsies. Gene‐expression profiles of paired tape‐strips and biopsies demonstrated a medium correlation (R2 = 0.431). Tape‐strips and biopsies demonstrated systematic differences in measured expression levels of 6483 genes across both AD and non‐AD samples. Tape‐strips preferentially detected many itch (CCL3/CCL4/OSM) and immune‐response (CXCL8/IL4/IL5/IL22) genes as well as markers of epidermal dendritic cells (CD1a/CD207), while certain cytokines (IL18/IL37), skin‐barrier genes (KRT2/FLG2), and dermal fibroblasts markers (COL1A/COL3A) were preferentially detected by biopsies. Tape‐strips identified more DEGs between AD and non‐AD (3157 DEGs) then biopsies (44 DEGs). Tape‐strips also detected higher levels of bacterial mRNA than biopsies.

Conclusions

This study concludes that tape‐strips and biopsies each demonstrate respective advantages for measuring gene‐expression changes in AD. Thus, the specific skin layers and genes of interest should be considered before selecting either method.
Factors affecting the use of a three‐dimensional model during robot‐assisted partial nephrectomy
Authors: Yamazaki Masahiro , Takayama Tatsuya , Sugihara Toru , Kikuchi Tomohiro , Kamimura Tomoki , Kamei Jun , Ando Satoshi , Terauchi Fumihito , Morita Tatsuo , Fujimura Tetsuya
Published: March 2024

Introduction

This study aimed to identify cases that require a three‐dimensional‐printed kidney model in robot‐assisted partial nephrectomy.

Methods

We enrolled 93 patients undergoing robot‐assisted partial nephrectomy for renal tumors at a single institution between November 2018 and May 2021. The endpoints were how often and how long the surgeon consulted the three‐dimensional‐printed model, determined using intraoperative video. Multivariate analyses of the endpoints were adjusted by preoperative patient and kidney characteristics, including renal vascular complexity that was defined as the number of vascular branches penetrating the surface tangential to the ventral side of the kidney.

Results

Of the 93 cases, the median frequency and duration of intraoperative three‐dimensional‐printed model consultation were four times and 39 s, respectively. The multivariate linear regression analyses showed that the frequency of intraoperative three‐dimensional‐printed model consultation by the surgeon was significantly related to the complexity of the arterial structure (≥4 branches), presence of hilar tumor, and high Mayo Adhesive Probability score; the regression coefficients were 1.81, 2.79, and 1.34, respectively. All p‐values were ≤.03. The duration of the three‐dimensional‐printed model consultation was significantly related to the complexity of the arterial structure (≥4 branches) and the presence of hilar tumor; the regression coefficients were 21.6, and 29.0 s, respectively. All p‐values were <.01.

Conclusion

During robot‐assisted partial nephrectomy, a three‐dimensional‐printed model would be helpful in cases with a complex arterial structure or hilar tumor.
Functional specialisation and coordination of myonuclei
Authors: Korb Amaury , Tajbakhsh Shahragim , Comai Glenda E.
Published: March 2024

Myofibres serve as the functional unit for locomotion, with the sarcomere as fundamental subunit. Running the entire length of this structure are hundreds of myonuclei, located at the periphery of the myofibre, juxtaposed to the plasma membrane. Myonuclear specialisation and clustering at the centre and ends of the fibre are known to be essential for muscle contraction, yet the molecular basis of this regionalisation has remained unclear. While the ‘myonuclear domain hypothesis’ helped explain how myonuclei can independently govern large cytoplasmic territories, novel technologies have provided granularity on the diverse transcriptional programs running simultaneously within the syncytia and added a new perspective on how myonuclei communicate. Building upon this, we explore the critical cellular and molecular sources of transcriptional and functional heterogeneity within myofibres, discussing the impact of intrinsic and extrinsic factors on myonuclear programs. This knowledge provides new insights for understanding muscle development, repair, and disease, but also opens avenues for the development of novel and precise therapeutic approaches.
LncRNA CTBP1‐AS inhibits TP63‐mediated activation of S100A14 during prostate cancer progression
Authors: Wu Guangzheng , Dong Zhenkun , Dong Yuhang , Chen Yinmei , Zhu Huan , Ding Dexin , Cui Yan , Wang Yiwen , Xu Yangyang , Chen Hui
Published: March 2024

Long noncoding RNAs (lncRNAs) have emerged as important molecules and potential new targets for human cancers. This study investigates the function of lncRNA CTBP1 antisense RNA (CTBP1‐AS) in prostate cancer (PCa) and explores the entailed molecular mechanism. Aberrantly expressed genes potentially correlated with PCa progression were probed using integrated bioinformatics analyses. A cohort of 68 patients with PCa was included, and their tumor and para‐cancerous tissues were collected. CTBP1‐AS was highly expressed in PCa tissues and cells and associated with poor patient prognosis. By contrast, tumor protein p63 (TP63) and S100 calcium binding protein A14 (S100A14) were poorly expressed in the PCa tissues and cells. CTBP1‐AS did not affect TP63 expression; however it blocked the TP63‐mediated transcriptional activation of S100A14, thereby reducing its expression. CTBP1‐AS silencing suppressed proliferation, apoptosis resistance, migration, invasion, and tumorigenicity of PCa cell lines, while its overexpression led to inverse results. The malignant phenotype of cells was further weakened by TP63 overexpression but restored following artificial S100A14 silencing. In conclusion, this study demonstrates that CTBP1‐AS plays an oncogenic role in PCa by blocking TP63‐mediated transcriptional activation of S100A14. This may provide insight into the management of PCa.
ctDNA predicts clinical T1a to pathological T3a upstaging after partial nephrectomy
Authors: Park Jee Soo , Kim Hongkyung , Jang Won Sik , Kim Jongchan , Ham Won Sik , Lee Seung‐Tae
Published: March 2024

Most patients diagnosed with clear cell renal cell carcinoma (ccRCC) are also detected with small and organ‐confined tumors, and the majority of these are classified as clinical tumor stage 1a (cT1a). A considerable proportion of patients with cT1 RCC shows tumor upstaging to pathological stage 3a (pT3a), and these patients have worse oncological outcomes. The role of circulating tumor DNA (ctDNA) in RCC has been limited to monitoring treatment response and resistance. Therefore, the present study aimed to evaluate the potential of ctDNA in predicting pT3a upstaging in cT1a ccRCC. We sequenced plasma samples preoperatively collected from 48 patients who had undergone partial nephrectomy for cT1a ccRCC using data from a prospective cohort RCC. The ctDNA were profiled and compared with clinicopathological ccRCC features to predict pT3a upstaging. Associations between ctDNA, tumor complexity, and pT3a upstaging were evaluated. Tumor complexity was assessed using the anatomical classification system. Univariate analysis used chi‐squared and Student's t‐tests; multivariate analysis considered significant factors from univariate analyses. Of the 48 patients with cT1a ccRCC, 12 (25%) were upstaged to pT3a, with ctDNA detected in 10 (20.8%), predominantly in patients with renal sinus fat invasion (SFI; n = 8). Among the pT3a group, ctDNA was detected in 75%, contrasting with only 2.8% in patients with pT1a (1/36). Detection of ctDNA was the only significant preoperative predictor of pT3a upstaging, especially in SFI. This study is the first to suggest ctDNA as a preoperative predictor of pT3a RCC upstaging from cT1a based on preoperative radiological images.
Asiatic acid inhibits rheumatoid arthritis fibroblast‐like synoviocyte growth through the Nrf2/HO‐1/NF‐κB signaling pathway
Authors: Zhang Li , Liu Zhi‐ning , Han Xi‐yuan , Liu Xin , Li Yang
Published: March 2024

Asiatic acid (AA) is generally recognized in the treatment of various diseases and has significant advantages in the treatment of various inflammatory diseases. The treatment of rheumatoid arthritis (RA) with AA is a completely new entry point. RA is a complex autoimmune inflammatory disease, and despite the involvement of different immune and nonimmune cells in the pathogenesis of RA, fibroblast‐like synoviocytes (FLS) play a crucial role in the progression of the disease. si‐Nrf2 was transfected in RA‐FLS and the cells were treated with AA. MTT assay and colony formation assay were used to detect the effect of AA on the viability and formation of clones of RA‐FLS, respectively. Moreover, the apoptosis of RA‐FLS was observed by Hoechst 33342 staining and flow cytometry. Western blot was applied to measure the expression of the Nrf2/HO‐1/NF‐κB signaling pathway‐related proteins. Compared with the control group, RA‐FLS proliferation, and clone formation were significantly inhibited by the increase of AA concentration, and further experiments showed that AA‐induced apoptosis of RA‐FLS. In addition, AA activated the Nrf2/HO‐1 pathway to inhibit NF‐κB protein expression. However, the knockdown of Nrf2 significantly offsets the effects of AA on the proliferation, apoptosis, and Nrf2/HO‐1/NF‐κB signaling pathway of RA‐FLS cells. AA can treat RA by inhibiting the proliferation and inducing the apoptosis of RA‐FLS. The mechanism may be related to the activation of the Nrf2/HO‐1/NF‐κB pathway.
Serum exosomal miR‐3662 down‐regulates the expression of RBMS3 to promote malignant progression and gemcitabine resistance of breast cancer cells
Authors: Li Xiang , Chu Xu , Wang Hao , Xiang Ling , Yue Xuandi
Published: March 2024

Breast cancer (BC) is a prevalent malignancy among women worldwide. As an anticancer drug of pyrimidine nucleoside analogs, gemcitabine can be used to treat BC, but its clinical application is restricted due to drug resistance. This study investigated the effect of serum exosomal microRNA‐3662 (miR‐3662) on gemcitabine resistance in BC cells by targeting RNA‐Binding Motif Single‐Stranded Interacting Protein 3 (RBMS3) and related molecular mechanisms. We performed the bioinformatics analyses on the differential miRNAs in BC and predicted the downstream regulators. Quantitative real‐time polymerase chain reaction was conducted to determine miR‐3662 and RBMS3 expression, while dual luciferase was conducted to confirme the regulatory relationship between them. Flow cytometry, cell counting kit‐8, and transwell assays were applied to assess apoptosis, cell viability, invasion, and migration. The expression of marker proteins (TSG101, CD63, and CD81) in patients' serum exosomes was evaluated through western blot, and exosomes were observed using transmission electron microscopy. miR‐3662 expression was significantly upregulated in BC, and miR‐3662 knockdown significantly reduced BC cell viability and gemcitabine resistance. As the downstream gene of miR‐3662, RBMS3 was significantly downregulated in BC, and dual luciferase assay verified the binding of RBMS3‐3′UTR to miR‐3662. Rescue experiments revealed that silencing RBMS3 reversed the inhibitory effect of miR‐3662 knockdown on BC cells. Besides, we also found that miR‐3662 expression was significantly low in serum exosome samples from BC patients and could be transmitted to tumor cells. miR‐3662 was upregulated in serum exosomes and promoted BC cell progression and gemcitabine resistance by targeting RBMS3.
Educational identity processes in adolescence: An analysis of longitudinal evidence and the role of educational systems
Authors: Negru‐Subtirica Oana
Published: March 2024

Educational identity has been studied increasingly in the past decades since school is a structured context that shapes adolescent identity formation. Across the academic years, adolescents learn to position themselves in terms of their education and schooling, perceiving these entities as more or less relevant for their self‐formation. In this article, I analyze educational identity in the context of personal identity formation in adolescence through longitudinal studies from Japan, the Netherlands, and Romania that used the identity process approach. I also examine the role educational systems play in educational identity trajectories, outlining the limits of personal intentionality when adolescents make educational choices. In addition, I address the relations of educational identity development with two important outcomes of education: academic achievement and vocational development. I conclude that educational identity formation reflects the freedom or coercion that country‐specific educational systems teach adolescents through educational tracking and the timing of educational transitions.
Fracture resistance of hybrid ceramic abutments with different restoration lengths: A pilot study
Authors: D'haese Rani , Vervack Valentin , Tytgat Manon , Vandeweghe Stefan
Published: March 2024

Aim

In this pilot study, the fracture resistance of hybrid abutments with different restoration lengths was investigated.

Materials and Methods

Sixteen monolithic zirconia restorations of an upper right incisor were designed to fit a titanium base abutment. Eight central incisors had a crown length of 8 mm (T1) and the other half a length of 12 mm (T2). All crowns were cemented on the titanium base using a resin cement. After cementation, the samples were placed in a thermocycler for 5000 cycles. Fracture strength was measured using a universal test machine. Deformations and fractures of the samples were investigated.

Results

The mean fracture resistance of T1 was 515 N (SD 96 N, 339–650) and 305 N (SD 57 N, 234–408) for T2 (p < 0.001). Both groups showed deformation of the titanium base, with no significant difference between both groups (p = 0.200). A difference in fracture type (p = 0.013) was observed, with significantly more screw fractures occurring in group T1 (p = 0.026).

Conclusion

Within the limitations of this study, hybrid restorations with standard titanium base abutments can withstand forces that have been associated with chewing, irrespective of the crown length. However, the shorter crowns demonstrated more fatal fractures.
Quantifying assumptions underlying peak oxygen consumption equations across the body mass spectrum
Authors: Busque Vincent , Christle Jeffrey W. , Moneghetti Kegan J. , Cauwenberghs Nicholas , Kouznetsova Tatiana , Blumberg Yair , Wheeler Matthew T. , Ashley Euan , Haddad Francois , Myers Jonathan
Published: March 2024

The goal of this study is to quantify the assumptions associated with the Wasserman‐Hansen (WH) and Fitness Registry and the Importance of Exercise: A National Database (FRIEND) predictive peak oxygen consumption (pVO2) equations across body mass index (BMI). Assumptions in pVO2 for both equations were first determined using a simulation and then evaluated using exercise data from the Stanford Exercise Testing registry. We calculated percent‐predicted VO2 (ppVO2) values for both equations and compared them using the Bland–Altman method. Assumptions associated with pVO2 across BMI categories were quantified by comparing the slopes of age‐adjusted VO2 ratios (pVO2/pre‐exercise VO2) and ppVO2 values for different BMI categories. The simulation revealed lower predicted fitness among adults with obesity using the FRIEND equation compared to the WH equations. In the clinical cohort, we evaluated 2471 patients (56.9% male, 22% with BMI >30 kg/m2, pVO2 26.8 mlO2/kg/min). The Bland–Altman plot revealed an average relative difference of −1.7% (95% CI: −2.1 to −1.2%) between WH and FRIEND ppVO2 values with greater differences among those with obesity. Analysis of the VO2 ratio to ppVO2 slopes across the BMI spectrum confirmed the assumption of lower fitness in those with obesity, and this trend was more pronounced using the FRIEND equation. Peak VO2 estimations between the WH and FRIEND equations differed significantly among individuals with obesity. The FRIEND equation resulted in a greater attributable reduction in pVO2 associated with obesity relative to the WH equations. The outlined relationships between BMI and predicted VO2 may better inform the clinical interpretation of ppVO2 values during cardiopulmonary exercise test evaluations.
Free‐ranging livestock reduces the habitat suitability of subalpine pheasants during breeding season in Southwest China
Authors: Shang Xiao‐Tong , Fan Fan , Shen Xiao‐Li , Zheng Yong , Zhao Lian‐Jun , Sun Hong‐Ou , Li Sheng , Zhang Li
Published: March 2024

Free‐ranging livestock pose a threat to forest biodiversity, exerting a profound influence on the survival of several endangered species. The mountains of Southwest China represent a biodiversity hotspot enriched with pheasant species of global significance; however, the influence of free‐ranging livestock on the survival and population of forest pheasants remains unclear. We examined the impact of livestock on the habitat suitability of subalpine pheasants and the associated mechanism during the breeding season in Southwest China (forest with and without grazing) over 2 years (2018–2019). Artificial nest experiments monitored by infrared‐triggered cameras showed that the nest failure rate was 2.18 folds higher in livestock‐active areas, where livestock directly accounted for 26.09% of all nest predation events, compared with other areas. Small animal trapping and vegetation quadrat surveys showed a 46% lower abundance of ground invertebrates, a critical food resource for breeding pheasants and their chicks, in grazing areas than in grazing‐free areas. Thus, livestock grazing markedly reduces the habitat suitability of subalpine pheasants during the breeding season. These results highlight the impacts of grazing on endangered pheasant species and the underlying mechanisms, necessitating centralized livestock management in these protected areas from April to July, coupled with livelihood transformation initiatives.
Pharmacokinetics and safety of erenumab in pediatric patients with migraine: A phase I, randomized, open‐label, multiple‐dose study
Authors: Hershey Andrew D. , Paiva da Silva Lima Gabriel , Pannacciulli Nicola , Mackowski Mia , Koukakis Reija , McVige Jennifer Williams
Published: March 2024

Erenumab, a fully human monoclonal antibody targeting the calcitonin gene‐related peptide receptor, is efficacious and safe for prevention of attacks of migraine in adults. This phase I, randomized, open‐label, multiple‐dose study evaluated the safety, tolerability, and pharmacokinetics (PK) of erenumab in children and adolescents with migraine. The initial treatment phase lasted 12 weeks, followed by an optional 40‐week extension phase for adolescents. Primary end points were PK of erenumab, incidence of treatment‐emergent adverse events (TEAEs), and changes in clinical and laboratory assessments. Participants received erenumab 35 mg (n = 4), 70 mg (n = 17), or 140 mg (n = 32) q4w. The mean age was 14.1 years. Of the 53 participants, 48 (90.6%) completed the initial treatment phase and 36 (67.9%) received erenumab during the extension phase. Mean exposures to erenumab based on the maximum observed concentration and the area under the drug concentration–time curve during the dosing interval increased approximately dose‐proportionally. A total of 42 participants (79.2%) reported TEAEs (307.2 per 100 participant‐years); and four (7.5%) reported serious TEAEs not considered treatment‐related. The most common TEAEs were upper respiratory tract infection, headache, and vomiting. No clinically significant changes were reported in vital signs, electrocardiograms, and laboratory and neurological assessments. Overall, the observed PK profile of erenumab in children and adolescents with migraine is consistent with that in adults when body weight differences are taken into consideration. The safety profile of erenumab in children and adolescents is consistent with that in adults.
Pharmacogenetics of tamoxifen in breast cancer patients of African descent: Lack of data
Authors: Kruger Bianca , Shamley Delva , Soko Nyarai Desiree , Dandara Collet
Published: March 2024

Tamoxifen, a selective estrogen receptor modulator, is used to treat hormone receptor‐positive breast cancer. Tamoxifen acts as a prodrug, with its primary therapeutic effect mediated by its principal metabolite, endoxifen. However, tamoxifen has complex pharmacokinetics involving several drug‐metabolizing enzymes and transporters influencing its disposition. Genes encoding enzymes involved in tamoxifen disposition exhibit genetic polymorphisms which vary widely across world populations. This review highlights the lack of data on tamoxifen pharmacogenetics among African populations. Gaps in data are described in this study with the purpose that future research can address this dearth of research on the pharmacogenetics of tamoxifen among African breast cancer patients. Initiatives such as the African Pharmacogenomics Network (APN) are crucial in promoting comprehensive pharmacogenetics studies to pinpoint important variants in pharmacogenes that could be used to reduce toxicity and improve efficacy.
Measures of Relative and Absolute Convergence and Pro‐poor Growth with an Illustration based on China (2010–2018)
Authors: Bárcena‐Martin Elena , Silber Jacques , Zhang Yuan
Published: March 2024

Income mobility is a key issue for understanding the process of economic growth and distributional change. Some economists have used the concept of “pro‐poor growth” to examine, with individual‐level panel data, whether the poor benefit more than the rich from economic growth by tracking the extent of income mobility among different population subgroups. There is also literature in macroeconomics on the measurement of convergence. This paper introduces population‐weighted relative and absolute indices of mobility, convergence, and pro‐poor growth; it also distinguishes between anonymous and nonanonymous approaches to these issues. The empirical analysis is based on Chinese panel data for the period 2010–2018. In both absolute and relative terms, income growth in China was greater for individuals with an initially lower income but only for lower income deciles in relative terms. There was also an overall increase in individual welfare from anonymous and nonanonymous perspectives, which was higher among younger individuals. The welfare of the poor did not increase more than that of the nonpoor. These results shed light on the evolution of income distribution in China during the past decade's rapid economic growth.
Climbing the Export Quality Ladder: Role of Human Capital
Authors: He Xiaogang , Teng Ruifeng , Feng Dawei
Published: March 2024

This study assesses the effect of human capital expansion on China's export product quality. It employs the difference‐in‐differences (DID) framework based on a quasi‐natural experiment investigating the 1999 higher education enrollment expansion as the exogenous policy shock. The empirical results confirm that human capital expansion appreciably improved the quality of China's export products. Human capital expansion promoted the transformation and upgrading of old products and the development of new products in term of intensive margin; it strengthened the endowment advantages of incumbent high‐quality export enterprises while preventing low‐quality enterprises from entering the market through price competition on the extensive margin. This prevented quality decline. Further, the study reveals that the improvement effect driven by human capital came from both innovation‐induced and managerial efficiency improvement channels and was more prominent for large or foreign‐funded enterprises in the eastern region. Our findings highlight the role of human capital in China's remarkable export performance from an endogenous growth perspective.
Value‐added Tax and Leverage: Evidence from China's Value‐added Tax Rate Reform
Authors: Fang Hongsheng , Zhao Lexin , Liu Xiufen
Published: March 2024

This paper uses China's value‐added tax (VAT) rate reform as a quasi‐natural experiment to identify the impacts of VAT rate shocks on corporate financial leverage. The results indicate that the reform reduced corporate total leverage significantly. There was a decrease in short‐term leverage, but long‐term leverage showed no significant change. These results remained robust across a series of robustness checks. Mechanism analysis shows that increasing profitability and improving cash flows acted as intermediary channels for the reform's impact on leverage. The reform also contributed to the mitigation of the asset–liability mismatch problem and the reduction of debt risk, while having no apparent impact on corporate investments. Finally, enterprises with more elastic demand and those with lower intermediate input ratios were affected most by the deleveraging effect of the VAT rate reform. This study suggests how the VAT rate cut shaped corporate capital structure. It thus helps to explain the economic consequences of VAT rate shocks.
The informed consent process: An evaluation of the challenges and adherence of Ghanaian researchers
Authors: Blankson Paa‐Kwesi , Akumiah Florence , Laar Amos , Kearns Lisa , Owusu Samuel Asiedu
Published: March 2024

This study assessed challenges faced by researchers with the informed consent process (ICP). In‐depth interviews were used to explore challenges encountered by Investigators, Research assistants, Institutional Review Board members and other stakeholders. An electronic questionnaire was also distributed, consisting of Likert‐scale responses to questions on adherence to the ICP, which were derived from the Helsinki Declaration and an informed consent checklist of the US Department of Health and Human Research (HSS). Responses were weighted numerically and scores calculated for each participant. The median score of the level of adherence to the informed consent process was 93%. Most of the respondents (60%) cited the lack of time for the ICP to be a challenge, with 65% indicating a lengthy consent document to be the main challenge with the informed consent document. Challenges with language and communication were the dominant theme among informants. Despite the high adherence of Ghanaian researchers and research assistants to the ICP, challenges are still prevalent, requiring diligent and continuous efforts in research implementation.
Structure and vulnerability of the ichthyochory network in wetland forests of Central Amazonia
Authors: Costa Gilvan , Weiss Bianca , Piedade Maria Teresa Fernandez , Ferreira Efrem Jorge , Maltchik Leonardo
Published: March 2024

The interaction between fish and plants is vital for the dynamics of ecosystems since it influences plant distribution and regeneration patterns. In the floodable areas of the Amazon, these interactions are mainly structured by the flood pulse, which enables seed dispersal via water (hydrochory) and fish (ichthyochory), and which contributes to the formation of complex mutualistic networks. Our study evaluated the structure (modularity, nestedness, specialisation, and robustness) of the network of dispersal of seeds by frugivorous fish in a floodplain forest in Central Amazonia. We expect the binary network to have a nested pattern, while the weighted network is expected to have a non‐nested structure; that generalist frugivorous species should constitute the core of the network, while specialist frugivorous species will be peripheral; that the size of fish and seeds is related to specialisation, and that the robustness of the network weakens as generalist frugivorous fish are removed. We found 5012 intact seeds from 49 plant species in the digestive tracts of 11 species of frugivorous fish. A nested and modular pattern was found for the binary and weighted networks, albeit with a low degree of nestedness. Our network proved relatively robust when the frugivores were removed, whereby all the fish and plant species became peripheral. No relationship was found between the size of the fish and the seeds and the degree of specialisation. Considering the anthropogenic impacts that can cause modifications in seed dispersal networks, knowing the structure of mutualistic networks is fundamental in order to be able infer the vulnerability of the interactions as a result of changes in the ecosystem.
Supporting second chance education: Drop‐in students' views on educational barriers and needs to study
Authors: Van Den Berghe Lana , Naert Jan , Vandevelde Stijn , De Pauw Sarah S. W.
Published: March 2024

In many Western societies, earning a degree is considered an ultimate educational achievement. Second chance education (SCE) serves as a distinct pathway for those who have dropped out of school, allowing them to re‐enter the educational system. Understanding the specific obstacles and needs of students in SCE is crucial for providing better‐tailored support. However, limited knowledge exists about the challenges faced by students seeking to enrol in SCE. This qualitative study conducted in‐depth interviews with 28 drop‐in students (Mage = 30) to explore these barriers and needs. Identified barriers span institutional, situational, environmental, and life‐course levels. Primary needs centre around warm and accessible teachers, as well as flexible, student‐focused learning options. The results underscore the value and significance of second chance education as a unique pedagogical context for drop‐in students. It also emphasizes that the insights gained from SCE can inform improvements in regular, first‐chance education, serving diverse student populations. Lastly, SCE serves as a societal mirror, urging a re‐evaluation of the broader discourse in education. Overall, this study calls for more appreciation of SCE, acknowledging and recognizing its unique pedagogical context, dedicated teachers, and determined students.
An assessment of potential herbivory impacts of a reintroduced marsupial in a predator‐free woodland sanctuary
Authors: O'Loughlin Luke S. , Baines Greg , Carlson Emma , Wimpenny Claire , Cooney Rosie
Published: March 2024

Fenced sanctuaries that exclude feral predators are critical for threatened species conservation. However, adaptive management of these sanctuaries requires careful consideration of the potential impact herbivore populations free from predation can have on the condition of native vegetation. The Mulligans Flat Woodland Sanctuary in the Australian Capital Territory comprises Critically Endangered box‐gum grassy woodland, threatened orchids, abundant macropods, and a reintroduced population of the Eastern Bettong (Bettongia gaimardi, hereafter “Ngaluda”). To understand how Ngaluda, along with other herbivores, may be potentially impacting vegetation across the sanctuary, we undertook an assessment of indicator plant species. We monitored 106 plots for 13 indicator species (10 species with tuberous roots that the burrowing Ngaluda would be preferentially targeting and three non‐tuberous species). We found that most floristic indicators we investigated – including richness of indicator species and the abundance of lilies – were higher in the Goorooyarroo area of the sanctuary (where Ngaluda are absent and wallabies are rare) compared to the Mulligans Flat area of the sanctuary (where Ngaluda are present and wallabies are abundant), suggesting a negative impact of the overall herbivore assemblage of Mulligans Flat. However, within just Mulligans Flat, some indicators, including the abundance of a common orchid, were significantly lower in areas associated with high Ngaluda activity irrespective of other herbivore densities. We found no instance of Ngaluda presence or higher activity being associated with higher values for any floristic indicator we investigated. These results are consistent with known impacts of abundant herbivores and reintroduced digging marsupials in other predator‐free sanctuaries in Australia. Our results highlight that Ngaluda herbivory may be outweighing any positive effect of their diggings on native vegetation and indicate the need for careful risk mitigation when deciding how critically endangered animals and vegetation communities are managed together in sanctuaries.
Endogeneity and causal attributions in management research: Some reflections and proposals
Authors: Giarratana Marco S.
Published: March 2024

This article explores the pivotal role of causal identification in the domain of management research and its alignment with theory creation. It seeks to stimulate thought about how researchers can approach theories and their causal identification with a review of the canonical methods. The article first addresses the intricacies of identification and the principal methodologies that researchers have recently employed in their investigations. Subsequently, it delves into the inherent costs associated with identification, specifically the need for additional assumptions, and the potential constraints on generalizability. It also promotes a more thoroughly examination of the nature of endogeneity. Finally, it explores how the link between causal identification and theory legitimacy could generate superstitious trajectories.
Antimanic‐like effect of dipyridamole in the methylphenidate‐induced hyperlocomotion
Authors: Santos Anderson Gustavo , Kühl Carlos Eduardo , Higashijima Arisa Namie , Kanazawa Luiz Kae Sales , de Souza Suzen Tortato Furtado , Andreatini Roberto
Published: March 2024

Background

Adenosinergic system has been implicated in the pathophysiology of bipolar disorder and drugs that affect adenosine neurotransmission have shown some efficacy as add‐on therapy in manic patients.

Objective

Thus, the aim of the present study was to screen adenosinergic drugs for antimanic‐like effect in methylphenidate (MPH)‐induced hyperlocomotion in mice.

Methods

Male and female Swiss mice received a single allopurinol (50 and 200 mg/kg, ip), dipyridamole (20 mg/kg, ip), or inosine (50 mg/kg, ip) administration before an acute MPH challenge (5 mg/kg, sc). In experiments with repeated treatment, male mice received a daily administration of allopurinol (25 and 50 mg/kg, ip), dipyridamole (20 mg/kg, ip), or inosine (50 mg/kg, ip) for 14 days. Finally, pretreatment with aminophylline (2 mg/kg, sc), an unspecific adenosine receptor antagonist, was used to evaluate a putative adenosinergic mediation. Locomotor activity was measured in the automated activity chamber for 20 min.

Results

Acute and repeated dipyridamole reduced the increase in locomotor activity induced by MPH, while allopurinol and inosine had no effect. Aminophylline blocked the effect of dipyridamole in MPH‐induced hyperlocomotion.

Conclusion

The present results suggest that dipyridamole may have an antimanic‐like effect through adenosine receptors and reinforce the proposal that the adenosine system may be an interesting target for new antimanic drugs.
Evidence of marine predation on silver New Zealand longfin eels, Anguilla dieffenbachii
Authors: Jellyman Donald , Franklin Paul , Aarestrup Kim , Birnie‐Gauvin Kim , Baker Cindy , Jellyman Phillip
Published: March 2024

The use of Pop‐up Satellite Archival Tags (PSATs) has provided considerable new information about the behaviour of migrating (silver) eels (Anguilla spp.) at sea, with 9 of 19 recognised species or subspecies tagged to date. However, such studies often reported premature tag detachment and relatively high rates of predation. Since 2000, several PSAT‐tagged New Zealand longfin eels, Anguilla dieffenbachii, were released to understand migratory behaviour and location of potential spawning grounds. Of 20 PSAT‐tagged eels released in 2019, all tags detached prematurely, but 7 (58%) were likely eaten or injured by predators 1–81 days after release. Two eels were probably eaten by sperm whales, whereas other tagged eels were likely eaten by lamniform and non‐lamniform sharks, and southern bluefin tuna. Because of the high rate of predation, we recommend that future releases should be from smaller catchments or offshore.
In‐depth investigation of FAM20A insufficiency effects on deciduous dental pulp cells: Altered behaviours, osteogenic differentiation, and inflammatory gene expression
Authors: Sriwattanapong Kanokwan , Theerapanon Thanakorn , Khamwachirapitak Chompak , Sae‐ear Pannagorn , Sa‐Ard‐Iam Noppadol , Shotelersuk Vorasuk , Porntaveetus Thantrira
Published: March 2024

Aim

Loss‐of‐function mutations in FAM20A result in amelogenesis imperfecta IG (AI1G) or enamel‐renal syndrome, characterized by hypoplastic enamel, ectopic calcification, and gingival hyperplasia, with some cases reporting spontaneous tooth infection. Despite previous reports on the consequence of FAM20A reduction in gingival fibroblasts and transcriptome analyses of AI1G pulp tissues, suggesting its involvement in mineralization and infection, its role in deciduous dental pulp cells (DDP) remains unreported. The aim of this study was to evaluate the properties of DDP obtained from an AI1G patient, providing additional insights into the effects of FAM20A on the mineralization of DDP.

Methodology

DDP were obtained from a FAM20A‐AI1G patient (mutant cells) and three healthy individuals. Cellular behaviours were examined using flow cytometry, MTT, attachment and spreading, colony formation, and wound healing assays. Osteogenic induction was applied to DDP, followed by alizarin red S staining to assess their osteogenic differentiation. The expression of FAM20A‐related genes, osteogenic genes, and inflammatory genes was analysed using real‐time PCR, Western blot, and/or immunolocalization. Additionally, STRING analysis was performed to predict potential protein–protein interaction networks.

Results

The mutant cells exhibited a significant reduction in FAM20A mRNA and protein levels, as well as proliferation, migration, attachment, and colony formation. However, normal FAM20A subcellular localization was maintained. Additionally, osteogenic/odontogenic genes, OSX, OPN, RUNX2, BSP, and DSPP, were downregulated, along with upregulated ALP. STRING analysis suggested a potential correlation between FAM20A and these osteogenic genes. After osteogenic induction, the mutant cells demonstrated reduced mineral deposition and dysregulated expression of osteogenic genes. Remarkably, FAM20A, FAM20C, RUNX2, OPN, and OSX were significantly upregulated in the mutant cells, whilst ALP, and OCN was downregulated. Furthermore, the mutant cells exhibited a significant increase in inflammatory gene expression, that is, IL‐1β and TGF‐β1, whereas IL‐6 and NFκB1 expression was significantly reduced.

Conclusion

The reduction of FAM20A in mutant DDP is associated with various cellular deficiencies, including delayed proliferation, attachment, spreading, and migration as well as altered osteogenic and inflammatory responses. These findings provide novel insights into the biology of FAM20A in dental pulp cells and shed light on the molecular mechanisms underlying AI1G pathology.