bluuebunny/crossref_metadata_2025 huggingface dataset:
Time trend analysis of rare cancer incidence 2011–2018: Nationwide population‐based cancer registries in Japan
Authors: Sugiyama Hiromi , Konda Manami , Saika Kumiko , Matsuda Tomohiro
Published: April 2024

Rare cancers collectively account for a significant proportion of the overall cancer burden in Japan. We aimed to describe and examine the incidence of each rare cancer and the temporal changes using the internationally agreed rare cancer classification. Cancer cases registered in regional population‐based cancer registries from 2011 to 2015 and the National Cancer Registry (NCR) from 2016 to 2018 were classified into 18 families, 68 Tier‐1 cancer groupings, and 216 single cancer entities based on the RARECAREnet list. Crude incidence rates and age‐standardized incidence rates (ASR) were calculated for Tier‐1 and Tier‐2 cancers. The annual percent change and the 95% and 99% confidence limits for annual ASR for each of the 68 Tier‐1 cancers were estimated using the log‐linear regression of the weighted least squares method. The differences in ASRs between 2011 and 2018 were evaluated as an absolute change. A total of 5,640,879 cases were classified into Tier‐1 and Tier‐2 cancers. The ASRs of 18 out of 52 Tier‐1 cancers in the rare cancer families increased, whereas the ASR for epithelial tumors of gallbladder decreased. The ASRs of 6 out of the 16 Tier‐1 cancers in the common cancer families increased, whereas those of epithelial tumors of stomach and liver decreased. There was no significant change in the incidence of the other 40 Tier‐1 cancers. The incidence of several cancers increased due to the dissemination of diagnostic concepts, improved diagnostic techniques, changes in coding practice, and the initiation of the NCR.
Pyroptotic macrophages promote proliferation and chemotherapy resistance of peripheral T‐cell lymphoma via TLR4 signaling pathway
Authors: Zhang Han , Li Liru , Zhang Zijian , Gao Shiqi , Yang Mingzhe , Ma Wenjie , Li Hongbin , Zhao Wenhui , Yang Huike , Zhang Yue , Zhao Shu
Published: April 2024

Peripheral T‐cell lymphoma (PTCL) is a highly aggressive type of non‐Hodgkin's lymphoma with a poor prognosis. Pyroptosis is a newly discovered procedural cell death mode, which has been implicated to occur in both tumor cells and immune cells. However, the occurrence and effect of pyroptosis on PTCL remain unclear. Here, we found that pyroptosis occurred in interstitial macrophages of PTCL rather than in tumor cells. In clinical specimens, macrophage pyroptosis was associated with a poor prognosis of PTCL. In vitro experiments and gene sequencing results showed that pyroptotic macrophages could upregulate the expression of TLR4 through secreting inflammatory cytokines IL‐18. Upregulated TLR4 activated its downstream NF‐κB anti‐apoptotic signaling pathway, thus leading to malignant proliferation and chemotherapy resistance of tumor cells. Moreover, the expression of factors such as XIAP in the NF‐κB anti‐apoptotic pathway was downregulated after the knockdown of TLR4, and the malignant promotion effect of pyroptotic macrophages on PTCL cells was also reversed. Our findings revealed the mechanism of pyroptotic macrophages promoting the malignant biological behavior of PTCL and elucidated the key role of TLR4 in this process. In‐depth analysis of this mechanism will contribute to understanding the regulatory effect of PTCL by the tumor microenvironment and providing new ideas for the clinical treatment of PTCL.
Cytotoxic activity and cell specificity of a novel LHRH peptide drug conjugate, D‐Cys6‐LHRH vedotin, against ovarian cancer cell lines
Authors: Vankadara Subramanyam , Ke Zhiyuan , Wang Sifang , Foo Sin Yun , Gunaratne Jayantha , Lee May Ann , Koh Xiaoying , Chia C. S. Brian
Published: April 2024

Ovarian cancer is the most deadly female gynaecological malignancy in developed countries and new treatments are urgently needed. The luteinising hormone releasing hormone (LHRH) peptide drug conjugate Zoptarelin doxorubicin is one such potential new drug modality that entered clinical trials for treating LHRH receptor‐positive gynaecological cancers. However, development stopped after disappointing Phase 3 results in 2017. We believe the lack of efficacy was due to linker instability and payload potency. In this work, we replaced its linker‐toxin with vedotin (MC‐VC‐PABC‐MMAE), yielding the novel peptide drug conjugate D‐Cys6‐LHRH vedotin. A GI50 and cell specificity comparison against cancerous and non‐cancerous ovarian cell lines showed significantly superior bioactivity and selectivity over Zoptarelin doxorubicin (GI50 4 vs. 453 nM) and other chemotherapeutic drugs used for treating ovarian cancers. Our results suggest D‐Cys6‐LHRH vedotin can potentially be used as a treatment for ovarian cancer.
Comparative study of imaging and pathology of primary mucinous adenocarcinoma with different imaging manifestations
Authors: Han Jun , Gao Jie , Chen Demei , Du Mou , Wu Yuxin , Ma Xidong , Xie Mei , Han Hua , Wu Chongchong , Xue Xinying
Published: April 2024

Background

Pulmonary mucinous adenocarcinoma is a special type of lung cancer. Its imaging manifestations are diverse, which brings challenges to clinical diagnosis. However, its formation mechanism is unclear.

Objective

The objective of this study is to analyse the relevant mechanisms of the formation of pulmonary mucinous adenocarcinoma by observing its different imaging and pathological manifestations.

Data and methods

Retrospective analysis was conducted on imaging manifestations and pathological data of 103 patients with pulmonary mucinous adenocarcinoma confirmed intraoperatively or pathologically.

Results

Forty‐three patients had pulmonary mucinous adenocarcinoma with a solitary nodule/mass, 41 patients with localized pneumonia and 19 patients with diffuse pneumonia. Their CT manifestations included ‘falling snowflake sign’, ground‐glass opacity close to the heart, vacuous signs/honeycombing and withered tree branches. Under the microscope, all the three types of pulmonary mucinous adenocarcinoma had visibly formed mucus lakes but were made of tumour cells with totally different shapes, which included the goblet‐like shape (tall column‐like shape) and quasi‐circular shape. Tall column‐shaped tumour cells were negative or weakly positive for thyroid transcription factor‐1 (TTF‐1) and strongly positive for ALK mutation, whereas quasi‐circular tumour cells were positive for TTF‐1 and less positive for ALK mutation.

Conclusion

The different imaging manifestations of mucinous adenocarcinoma are possibly due to the different amounts or viscosity of mucus produced, and the mechanisms of its formation may include (1) tumour cells in different shapes have different abilities to produce mucus; (2) tumours in different stages produce different amounts or viscosity of mucus; and (3) the TTF‐1 and ALK genes affect the production of mucus.
Transplant nephropathology: Wherefrom, wherein, and whereto
Authors: Solez Kim , Eknoyan Garabed
Published: April 2024

Renal pathology is a relatively recent entry in nephrology. While diseases of the kidney are old, their study began in the 19th century with the report of Richard Bright of the lesions of end‐stage kidney disease. Its easy diagnosis from albuminuria soon elevated Bright's nephritis into a leading cause of death. The transformative events in the care of these cases were renal replacement therapy that converted a fatal into a chronic disease, and kidney biopsy that allowed study of the course and pathogenesis of kidney disease. Apart from its fundamental contributions to clinical nephrology, biopsy of renal allografts became an integral component of the evaluation and care of kidney transplant recipients. The Banff transplant pathology conferences launched in 1991 led to developing the classification of allograft pathology into an essential element in the evaluation, treatment, and care of allograft recipients with spirit of discovery. That success came at the cost of increasing complexity leading to the recent realization that it may need the refinement of its consensus‐based system into a more evidence‐based system with graded statements that are easily accessible to the other disciplines involved in the care of transplanted patients. Collaboration with other medical disciplines, allowing public comment on meeting reports, and incorporation of generative artificial intelligence (AI) are important elements of a successful future. The increased pace of innovation brought about by AI will likely allow us to solve the organ shortage soon and require new classifications for xenotransplantation pathology, tissue engineering pathology, and bioartificial organ pathology.
Feeling loved in mixed‐gender adolescent romantic relationships in the face of daily stress and support: A dyadic diary study
Authors: Ha Thao , Iida Masumi , Quiroz Selena I. , Maras Olivia , Savord Andrea
Published: April 2024

A profound developmental experience is the emergence of adolescent romantic relationships and first feelings of love. However, the daily nature of feeling loved in adolescents’ everyday lives is poorly understood. We investigated how daily stress severity was associated with adolescents’ levels of feeling loved and whether romantic partner support moderated these associations. Furthermore, we investigated this for non‐interpersonal and interpersonal stressors. N = 97 mixed‐gender adolescent romantic couples (age M = 16.38, SD = 1.02) from an ethnically diverse sample (42.2% Hispanic/Latino/a/x, 44.7% White) participated in dyadic diary assessments twice a week for 12 consecutive weeks. Both partners independently completed open‐ended questions about a daily stressor, indicating stress severity, perceived partner support, and feeling loved. Daily stressors were coded for non‐interpersonal and various types of interpersonal stressors. Results from the dyadic multilevel model showed that days with lower than average support from a romantic partner amplify the adverse effects of stress severity on feeling loved, especially when the partner is involved in the stressor. We discuss the spillover of stress in romantic relationships and the stress‐buffering functions of adolescent romantic partner support. Adolescent romantic partners are potentially essential regulators of stress, increasing adolescents’ feelings of love.

Research Highlights

Romantic love is central in adolescents’ lives; we showed that adolescents generally feel loved by romantic partners.

Feeling loved fluctuates daily as adolescents feel less loved on stressful days.

However, when adolescents perceive their partner as supportive, there is no association between stress and feeling loved. Partner support is protective for feeling loved.

The current study provides essential insights into when adolescents and why adolescents feel loved.
Baby Observational Selective Control AppRaisal (BabyOSCAR): Convergent and discriminant validity and reliability in infants with and without spastic cerebral palsy
Authors: Sukal‐Moulton Theresa , Barbosa Vanessa Maziero , Sargent Barbara , Boswell Lynn , de Regnier Raye‐Ann , Bos Arend F. , Peyton Colleen
Published: April 2024

Aim

To describe the development of an observational measure of spontaneous independent joint motion in infants with spastic cerebral palsy (CP), the Baby Observational Selective Control AppRaisal (BabyOSCAR), and to test its convergent validity and reliability.

Method

A retrospective sample of 75 infants (45 with spastic CP and 30 without CP) at 3 months of age were scored with the BabyOSCAR and compared with diagnosis of spastic CP, limbs affected, and Gross Motor Function Classification level at 2 years of age or later for convergent validity using t‐tests, Kruskal–Wallis tests, and Spearman's rank correlation coefficients. BabyOSCAR interrater and test–retest reliability was also evaluated using intraclass correlation coefficients.

Results

Infants with spastic CP had significantly lower BabyOSCAR scores than children without CP (p < 0.001) and scores were significantly correlated with Gross Motor Function Classification System levels (p < 0.001). Children with unilateral CP had significantly higher asymmetry scores than children with bilateral CP or no CP (p < 0.01). Interrater and test–retest reliabilities were good to excellent.

Interpretation

Reductions in independent joint control measured in infancy are a hallmark of eventual diagnosis of spastic CP, and influence gross motor function later in childhood (with or without a diagnosis of CP).

What this paper adds

Early brain injury causing spastic cerebral palsy results in fewer independent joint movements in infants.

Baby Observational Selective Control AppRaisal (BabyOSCAR) score at 3 months depends on limbs affected by early brain injury.

BabyOSCAR scores at 3 months correlate with Gross Motor Function Classification System level at ≥2 years.

BabyOSCAR has excellent interrater reliability.

BabyOSCAR, scored with a 1‐minute video recording, has good to excellent test–retest reliability.
The ABCG8 polymorphism increases the risk of gallbladder cancer in the general population and gallstones in obese patients from Poland
Authors: Krupa Lukasz , Kalinowski Piotr , Ligocka Joanna , Dauer Marc , Jankowski Krzysztof , Gozdowska Jolanta , Kruk Beata , Milkiewicz Piotr , Zieniewicz Krzysztof , Krawczyk Marek , Weber Susanne N. , Lammert Frank , Krawczyk Marcin
Published: April 2024

Background

Gallstone disease (GD) is common but remains asymptomatic in most cases. However, gallstones can lead to complications like choledocholithiasis or gallbladder cancer. In this study, we analyse the common genetic risk factor for GD, the p.D19H variant in the sterol transporter ABCG8, in Polish patients with gallstones and gallbladder cancer.

Methods

Three adult cohorts were prospectively recruited: 65 patients with gallbladder cancer, 170 obese individuals scheduled for bariatric surgery and 72 patients who underwent endoscopic retrograde cholangiopancreatography due to recurrent choledocholithiasis. The control cohort consisted of 172 gallstone‐free adults. The ABCG8 p.D19H (rs11887534) polymorphism was genotyped using TaqMan assays.

Results

The minor allele frequency (MAF) of the ABCG8 p.D19H polymorphism was significantly (p = .02) higher among cases with either gallstones or gallbladder cancer (MAF = 8.4%) as compared to controls (MAF = 4.0%). The highest frequency of the risk allele was detected in patients with gallbladder cancer (18.5%) and obese patients with GD (17.5%), followed by individuals with choledocholithiasis (13.9%). Notably, the p.19H variant was associated with an increased risk of developing gallbladder cancer (OR 2.76, 95% CI 1.16–6.54, p = .01) and an increased risk of GD in obese individuals scheduled for bariatric surgery (OR = 2.70, 95% CI 1.05–6.49, p = .03), but did not significantly affect the risk of choledocholithiasis.

Conclusions

The ABCG8 p.D19H common risk variant increases the risk of developing gallbladder cancer in Central Europeans and enhances the risk of gallstones in the obese. Carriers of the p.D19H variant might benefit from personalized preventive strategies, particularly regarding gallbladder cancer.
Rapid assessment of beech leaf disease in Fagus sylvatica buds
Authors: Wolf Emily , Vieira Paulo
Published: April 2024

The European beech (Fagus sylvatica) is threatened by the foliar nematode Litylenchus crenatae subsp. mccannii (Lcm), the causal agent of beech leaf disease (BLD). Thus far, the majority of studies regarding BLD have focused on American beech (F. grandifolia). To better determine the impact of Lcm in buds of European beech, a total of 54 buds were collected from naturally symptomatic trees. Here, we characterized for the first time the bud scale morphology of two different cultivars of F. sylvatica infected with Lcm. Detailed observations of asymptomatic and symptomatic bud scales provided insight into the physical changes and arrangements of cells in the bud scale, shedding light on the dynamic processes occurring during Lcm infection. In addition, we evaluated the suitability of using the bud scale morphology for the early detection of BLD and Lcm in naturally infected buds. The distinct cellular arrangement of symptomatic bud scales cells (i.e., asymmetric pattern of enlarged cells) provides a rapid and visual, user‐friendly methodology to prematurely diagnose BLD symptoms within the buds, as well as the detection of associated nematodes.
Teaching mathematics in innovative learning environments—The entangled tensions between the learning environment and pedagogy
Authors: Alakoski Riikka , Laine Anu , Hannula Markku S.
Published: April 2024

New school buildings are often designed for flexible innovative learning environments (ILEs) to support learning future skills better than before. However, little is known about the relationship between environment and pedagogy. This article examines the relationship between the environment and pedagogy from the perspective of primary school teachers in the context of teaching mathematics. We interviewed 26 teachers from 10 Finnish ILEs and did a thematic analysis. The relationship between the environment and pedagogy forms a complex network of entangled tensions between teacher's inner space, community's social space and physical space. When the tensions between these spaces were resolved in a positive way, ILEs enabled pedagogy that diversified mathematics education, improved student cohesion and teachers' well‐being at work. However, the ILEs' transformation process often appears to be left unfinished, leading to unsuccessful resolution of tensions. Further, our findings highlight the importance of four‐dimensional environmental competence in exploiting the affordances enabled by ILE.
Post‐transplant‐cyclophosphamide and short‐term Everolimus as graft‐versus‐host‐prophylaxis in patients with relapsed/refractory lymphoma and myeloma—Final results of the phase II OCTET‐EVER trial
Authors: Richardson Tim , Scheid Christof , Herling Marco , Frenzel Lukas P. , Herling Carmen , Aguilar Marta Rebecca Cruz , Theurich Sebastian , Hallek Michael , Holtick Udo
Published: April 2024

Background

Conditioning regimens and the choice of immunosuppression have substantial impact on immune reconstitution after allogeneic hematopoietic stem cell transplantation (aHSCT). The pivotal mechanism to maintain remission is the induction of the graft‐versus‐tumor effect. Relapse as well as graft versus host disease remain common. Classic immunosuppressive strategies implementing calcineurin inhibitors (CNI) have significant toxicities, hamper the immune recovery, and reduce the anti‐cancer immune response.

Methods

We designed a phase II clinical trial for patients with relapsed and refractory lymphoid malignancies undergoing aHSCT using a CNI‐free approach consisting of post‐transplant cyclophosphamide (PTCy) and short‐term Everolimus after reduced‐intensity conditioning and matched peripheral blood stem cell transplantation. The results of the 19 planned patients are presented. Primary endpoint is the cumulative incidence and severity of acute GvHD.

Results

Overall incidence of acute GvHD was 53% with no grade III or IV. Cumulative incidence of NRM at 1, 2, and 4 years was 11%, 11%, and 16%, respectively, with a median follow‐up of 43 months. Cumulative incidence of relapse was 32%, 32%, and 42% at 1, 2, and 4 years after transplant, respectively. Four out of six early relapses were multiple myeloma patients. Overall survival was 79%, 74%, and 62% at 1, 2, and 4 years. GvHD‐relapse‐free‐survival was 47% after 3 years.

Conclusions

Using PTCy and short‐term Everolimus is safe with low rates of aGvHD and no severe aGvHD or cGvHD translating into a low rate of non‐relapse mortality. Our results in this difficult to treat patient population are encouraging and warrant further studies.
Benefit corporation certification and financial performance: Capital structure matters
Authors: Asma‐Arikan Özlem , Tosun Onur Kemal
Published: April 2024

We are examining the impact of benefit corporation certification on the profitability of UK companies, taking into account their capital structure. We contribute to the literature that scrutinizes the financial ramifications of Benefit Corporation Certification. Analyzing UK Certified Benefit Corporations (CBCs) and their noncertified counterparts using a difference‐in‐differences analysis, we find that the performance of CBCs with a capital structure heavily weighted towards debt declines in comparison to non‐CBCs, using Return on Assets as a measure of financial performance. Conversely, the performance of CBCs with a capital structure primarily composed of equity is comparable to that of non‐CBCs.
A dilated convolution‐based method with time series fine tuning for data‐driven crack length estimation
Authors: Gao Jiaxin , Hu Wenbo , Han Qinan , Chen Yuntian , Hong Richang , Shi Huiji
Published: April 2024

This paper presents a novel crack size estimation method based on dilated convolution and time series fine tuning using in‐situ Lamb wave. The contributions of this proposed method are twofold: (1) a dilated convolution‐based neural network which is an effective representation learning methods with larger receptive fields for periodic signals and (2) a crack length adjustment approach based on previous estimations with a time series fine tuning method. The time series fine tuning method utilizes the monotonicity of the crack length with respect to time. A new evaluation metric has been adopted, which considers prediction errors, time errors, and monotonicity errors. The proposed method outperforms the previous feature extraction‐based methods with or without time series fine tuning in this new evaluation metric.
Angling bait consumption and stable isotope niche of two cyprinids in different lake fisheries
Authors: Imbert Alexis , Beisel Jean‐Nicolas , Boulêtreau Stéphanie , Cucherousset Julien
Published: April 2024

Terrestrial subsidies are important for freshwater ecosystems and, in lakes supporting recreational fisheries, angling baits can represent an important allochthonous input. This resource can directly contribute to fish diet but its consumption may be influenced by fish body size and the type of angling baits used in different fisheries. In this study, we evaluated angling baits consumption by two common cyprinid species, Cyprinus carpio and Rutilus rutilus, in three fishery types (specialised carp, specialised roach, and put‐and‐take fisheries).

We used stable isotope analyses (δ13C and δ15N) of cyprinids, their natural prey and different angling baits in 16 gravel pit lakes located in south‐western France, including four lakes without angling.

Angling baits were significantly δ13C‐enriched and δ15N‐depleted compared to natural prey. Overall, angling bait consumption was highly variable between individuals. For C. carpio, angling bait consumption averaged 30.5% (±17.0 SD) and was higher in specialised carp fisheries (40.0% ± 16.7 SD) than in put‐and‐take fisheries (15.9% ± 9.0 SD) and was not related to body size. For R. rutilus, angling bait consumption averaged 41.3% (±15.7 SD), did not differ significantly among fishery types, but increased with body size. The niche width of C. carpio was six times larger in specialised carp fisheries than in lakes without angling. For R. rutilus, niche width was two times larger in specialised carp and put‐and‐take fisheries compared to lakes without angling and specialised roach fisheries.

These results indicate that angling bait subsidies represent a novel and substantial resource opportunity for fishes in angling lakes, with trophic consequences for the targeted species through increase of their stable isotope niche size. These impacts are partly influenced by the type of angling baits used by anglers and the characteristics of the fisheries, suggesting the need for improved quantification of the temporal dynamics of this type of subsidy to better understand its consequences on freshwater fish and recipient ecosystems.
Predictors of Respiratory Syncytial Virus, Influenza Virus, and Human Metapneumovirus Carriage in Children Under 5 Years With WHO‐Defined Fast‐Breathing Pneumonia in Pakistan
Authors: Nisar Muhammad Imran , Kerai Salima , Shahid Shahira , Qazi Muhammad Farrukh , Rehman Sarah , Aziz Fatima , Jehan Fyezah
Published: April 2024

Background

Pneumonia is a leading cause of morbidity and mortality in children < 5 years. We describe nasopharyngeal carriage of respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and influenza virus among children with fast‐breathing pneumonia in Karachi, Pakistan.

Methods

We performed a cross‐sectional analysis of nasopharyngeal swabs from children aged 2–59 months with fast‐breathing pneumonia, enrolled in the randomized trial of amoxicillin versus placebo for fast‐breathing pneumonia (RETAPP) (NCT02372461) from 2014 to 2016. Swabs were collected using WHO standardized methods, processed at the Aga Khan University, Pakistan. Viral detection was performed using LUMINEX xTAG respiratory viral panel assay and logistic regression identified clinical and sociodemographic predictors.

Findings

Of the 1000 children tested, 92.2% (n = 922) were positive for viral carriage. RSV, hMPV, and influenza virus were detected in 59 (6.4%), 56 (6.1%), and 58 (6.3%) children and co‐infections in three samples (two RSV‐hMPV and one influenza‐hMPV). RSV carriage was common in infants (56%), we observed a higher occurrence of fever in children with hMPV and influenza virus (80% and 88%, respectively) and fast breathing in RSV (80%) carriage. RSV carriage was positively associated with a history of fast/difficulty breathing (aOR: 1.96, 95% CI 1.02–3.76) and low oxygen saturation (aOR: 2.52, 95% CI 1.32–4.82), hMPV carriage was positively associated with a complete vaccination status (aOR: 2.22, 95% CI 1.23–4.00) and body temperature ≥ 37.5°C (aOR: 2.34, 95% CI 1.35–4.04) whereas influenza viral carriage was associated with body temperature ≥ 37.5°C (aOR: 4.48, 95% CI 2.53–7.93).

Conclusion

We observed a high nasopharyngeal viral carriage among children with WHO‐defined fast‐breathing pneumonia in Pakistan. Fever, difficulty in breathing, hypoxia and vaccination status are important clinical predictors for viral nonsevere community‐acquired pneumonia.
The role of orthobiologics in chronic wound healing
Authors: Domingues Rafael Barnabé , von Rautenfeld Marita , Kavalco Caroline Mayara , Caliari Carolina , Dellagiustina Celso , da Fonseca Lucas Furtado , Costa Fabio Ramos , da Cruz Silva Reis Andreza , Santos Gabriel Silva , Azzini Gabriel , de Faria André Pinto Lemos , Santos Napoliane , Pires Luyddy , Huber Stephany Cares , Mahmood Ansar , Dallo Ignacio , Everts Peter , Lana José Fábio
Published: April 2024

Chronic wounds, characterized by prolonged healing processes, pose a significant medical challenge with multifaceted aetiologies, including local and systemic factors. Here, it explores the complex pathogenesis of chronic wounds, emphasizing the disruption in the normal phases of wound healing, particularly the inflammatory phase, leading to an imbalance in extracellular matrix (ECM) dynamics and persistent inflammation. Senescent cell populations further contribute to impaired wound healing in chronic lesions. Traditional medical management focuses on addressing underlying causes, but many chronic wounds resist to conventional treatments, necessitating innovative approaches. Recent attention has turned to autologous orthobiologics, such as platelet‐rich plasma (PRP), platelet‐rich fibrin (PRF) and mesenchymal stem cells (MSCs), as potential regenerative interventions. These biologically derived materials, including bone marrow aspirate/concentrate (BMA/BMAC) and adipose tissue‐derived stem cells (ADSCs), exhibit promising cytokine content and regenerative potential. MSCs, in particular, have emerged as key players in wound healing, influencing inflammation and promoting tissue regeneration. This paper reviews relevant scientific literature regarding basic science and brings real‐world evidence regarding the use of orthobiologics in the treatment of chronic wounds, irrespective of aetiology. The discussion highlights the regenerative properties of PRP, PRF, BMA, BMAC and SVF, showcasing their potential to enhance wound healing. Despite advancements, further research is essential to elucidate the specific roles of each orthobiologic and determine optimal applications for different wound types. The conclusion underscores the evolving landscape in chronic wound management, with a call for more comprehensive studies to refine treatment strategies and maximize the benefits of regenerative medicine.
Adaptive designs in dermatology clinical trials: Current status and future perspectives
Authors: Potvin D. , D'Angelo P. , Bennett S. , Jankicevic J. , Bissonnette R.
Published: April 2024

Current drug development strategies present many challenges that can impede drug approval by regulatory agencies. Alternative study models, such as adaptive trial designs, have recently sparked interest, as they provide a flexible and more efficient approach in conducting clinical trials. Adaptive trial designs offer several potential benefits over traditional randomized controlled trials, which include decrease in costs, reduced clinical development time and limiting exposure of patients to potentially ineffective treatments allowing completion of studies with fewer patients. This article explores the current use of adaptive trial designs in non‐oncologic skin diseases and highlights the most common types of adaptive designs used in the field. We also review the operational challenges and statistical considerations associated with such designs and propose clinical development strategies to successfully implement adaptive designs. The article also proposes instances where adaptive trial designs are particularly beneficial, and other situations where they may not be very useful.
Plasma and tissue transferrin and ferritin, and gene expression of ferritin, transferrin, and transferrin receptors I and II in channelcatfishIctalurus punctatusfed diets with different concentrations of inorganic or organic iron
Authors: Buyinza Isaac , Ramena Grace , Lochmann Rebecca , Sinha Amit , Jones Michele
Published: April 2024

Ferritin, transferrin, and transferrin receptors I and II play a vital role in iron metabolism, health, and indication of iron deficiency anaemia in fish. To evaluate the use of high‐iron diets to prevent or reverse channel catfish (Ictalurus punctatus) anaemia of unknown causes, we investigated the expression of these iron‐regulatory genes and proteins in channel catfish fed plant‐based diets. Catfish fingerlings were fed five diets supplemented with 0 (basal), 125, and 250 mg/kg of either inorganic iron or organic iron for 2 weeks. Ferritin, transferrin, and transferrin receptor I and II mRNA and protein expression levels in fish tissues (liver, intestine, trunk kidney, and head kidney) and plasma were determined. Transferrin (iron transporter) and TfR (I and II) genes were generally highly expressed in fish fed the basal diet compared to those fed the iron‐supplemented diets. In contrast, ferritin (iron storage) genes were more expressed in the trunk kidney of fish fed the iron‐supplemented diets than in those fed the basal diet. Our results demonstrate that supplementing channel catfish plant‐based diets with iron from either organic or inorganic iron sources affected the expression of the iron‐regulatory genes and increased body iron status in the fish.
Modulated illumination microscopy: Application perspectives in nuclear nanostructure analysis
Authors: Cremer Christoph , Schock Florian , Failla Antonio Virgilio , Birk Udo
Published: April 2024

The structure of the cell nucleus of higher organisms has become a major topic of advanced light microscopy. So far, a variety of methods have been applied, including confocal laser scanning fluorescence microscopy, 4Pi, STED and localisation microscopy approaches, as well as different types of patterned illumination microscopy, modulated either laterally (in the object plane) or axially (along the optical axis). Based on our experience, we discuss here some application perspectives of Modulated Illumination Microscopy (MIM) and its combination with single‐molecule localisation microscopy (SMLM). For example, spatially modulated illumination microscopy/SMI (illumination modulation along the optical axis) has been used to determine the axial extension (size) of small, optically isolated fluorescent objects between ≤ 200 nm and ≥ 40 nm diameter with a precision down to the few nm range; it also allows the axial positioning of such structures down to the 1 nm scale; combined with laterally structured illumination/SIM, a 3D localisation precision of ≤1 nm is expected using fluorescence yields typical for SMLM applications. Together with the nanosizing capability of SMI, this can be used to analyse macromolecular nuclear complexes with a resolution approaching that of cryoelectron microscopy.
Feasibility of measuring blood‐brain barrier permeability using ultra‐short echo time radial magnetic resonance imaging
Authors: Bae Jonghyun , Qayyum Sawwal , Zhang Jin , Das Ayesha , Reyes Isabel , Aronowitz Eric , Stavarache Mihaela A. , Kaplitt Michael G. , Masurkar Arjun , Kim Sungheon Gene
Published: April 2024

Background and Purpose

The purpose of this study is to evaluate the feasibility of using 3‐dimensional (3D) ultra‐short echo time (UTE) radial imaging method for measurement of the permeability of the blood‐brain barrier (BBB) to gadolinium‐based contrast agent. In this study, we propose to use the golden‐angle radial sparse parallel (GRASP) method with 3D center‐out trajectories for UTE, hence named as 3D UTE‐GRASP. We first examined the feasibility of using 3D UTE‐GRASP dynamic contrast‐enhanced (DCE)‐magnetic resonance imaging (MRI) for differentiating subtle BBB disruptions induced by focused ultrasound (FUS). Then, we examined the BBB permeability changes in Alzheimer's disease (AD) pathology using Alzheimer's disease transgenic mice (5xFAD) at different ages.

Methods

For FUS experiments, we used four Sprague Dawley rats at similar ages where we compared BBB permeability of each rat receiving the FUS sonication with different acoustic power (0.4‐1.0 MPa). For AD transgenic mice experiments, we included three 5xFAD mice (6, 12, and 16 months old) and three wild‐type mice (4, 8, and 12 months old).

Results

The result from FUS experiments showed a progressive increase in BBB permeability with increase of acoustic power (p < .05), demonstrating the sensitivity of DCE‐MRI method for detecting subtle changes in BBB disruption. Our AD transgenic mice experiments suggest an early BBB disruption in 5xFAD mice, which is further impaired with aging.

Conclusion

The results in this study substantiate the feasibility of using the proposed 3D UTE‐GRASP method for detecting subtle BBB permeability changes expected in neurodegenerative diseases, such as AD.
Health and health care are essential to the quality of life of people with intellectual disability
Authors: Bacherini Alice , Gómez Laura E. , Balboni Giulia , Havercamp Susan M.
Published: April 2024

Health represents the dynamic balance of physical, mental, social, and existential well‐being in adapting to conditions of life and the environment. Health is essential for the quality of life (QoL) of all individuals, including those with intellectual disability (ID). People with ID experience health inequities and barriers to quality health care that must be addressed to foster the QoL of this population. This paper illustrates how poor health negatively impacts each of the eight domains of the QoL model proposed by Shalock and Verdugo (2002) (e.g., health conditions limit work performance, decreasing opportunities for personal development and self‐determination). Suggestions for healthcare practices and behaviors that would improve the quality of healthcare provided to people with ID, and thus their health and QoL, are offered (e.g., engaging people with ID in the medical conversation, talking to them in plain language and without jargon enhances the personal development, self‐determination, interpersonal relationships, and social inclusion domains of QoL). Finally, we suggest actions that people with ID and their families might implement to maximize their health and wellness (e.g., maintaining a healthy lifestyle, and using the health promotion resources provided by disability organizations).
Exosomes miR‐92a‐3p from human exfoliated deciduous teeth inhibits periodontitis progression via the KLF4/PI3K/AKT pathway
Authors: Yu Tianliang , Mi Na , Song Yingtao , Xie Weili
Published: April 2024

Background

Periodontitis is a chronic inflammatory disease mediated by dysbiosis of the oral microflora, resulting in the destruction of periodontal tissue. Increasing evidence suggested that mesenchymal stem cell (MSCs) and exosomes derived from MSCs play a critical role in periodontal tissue regeneration. However, whether stem cells from exfoliated deciduous teeth (SHED)‐secreted exosomes can improve the therapeutic potential of periodontitis is largely unknown.

Objective

Here, we aim to evaluate the effect of SHED‐exosomes on inflammation, apoptosis and osteogenic differentiation in periodontitis.

Methods

The periodontitis cell model was constructed by stimulating periodontal ligament stem cells (PDLSCs) with lipopolysaccharide (LPS), and the periodontitis rats were established by ligation.

Results

First, we isolated exosomes from the SHED, and we figured out that exosomes secreted by SHED were enriched in miR‐92a‐3p and the exosomes enhanced proliferation and osteogenic differentiation and reduced apoptosis and inflammatory responses in PDLSCs. In addition, we found that SHED‐exosomes alleviated inflammatory effect and elevated the expression of osteogenic‐related genes in periodontitis rat model. Moreover, miR‐92a‐3p targeted downstream Krüppel‐Like Transcription Factor 4 (KLF4) and regulated the PI3K/AKT pathway. Finally, our data indicated that upregulation of KLF4 or activation of PI3K/AKT by 740Y‐P counteracted the inhibitory effect of SHED‐exosomes on periodontitis progression.

Conclusion

Taken together, our finding revealed that exosomal miR‐92a‐3p derived from SHED contributed to the alleviation of periodontitis development and progression through inactivating the KLF4/PI3K/AKT signaling pathway, which may provide a potential target for the treatment of periodontitis.
Long‐term performance of show‐jumping horses and relationship with severity of ataxia and complications associated with myeloencephalopathy caused by equine herpes virus‐1
Authors: de la Cuesta‐Torrado María , Velloso Alvarez Ana , Neira‐Egea Patricia , Cuervo‐Arango Juan
Published: April 2024

Background

Equine herpesvirus myeloencephalopathy (EHM) has severe impact on the sport horse population.

Objective

Study the influence of EHM on the likelihood of affected horses to return to their previous performance and investigate the association of clinical variables with prognosis.

Animals

Twenty‐six horses positive for equine herpesvirus type 1 (EHV‐1) were admitted to a veterinary teaching hospital (VTH) during a natural EHM outbreak at an international jumping event.

Methods

Data collected from the VTH, the International Equestrian Federation, and surveys completed by the riders and horse owners were retrospectively analyzed.

Results

Horses affected by EHM had 68% chance of returning to exercise, and 52.9% were able to achieve their preoutbreak performance level. Horses with an ataxia grade at admission ≥4/5 had an increased fatality rate (P < .05) and 10% chance of reaching their preoutbreak performance level. None of the horses with both vascular and urinary complications returned to their previous performance level. Finally, horses vaccinated against EHV‐1 and those with urinary complications had a 71.4% and 43.7% fatality rate, respectively.

Conclusions and Clinical Importance

Horses affected by EHM were able to return to their previous performance levels, but certain clinical variables were negatively associated with postoutbreak performance. Ataxia grade upon admission and the development of systemic signs of vasculitis and urinary complications were potential poor prognostic indicators in sport horses. Variables linked to fatality included prior vaccination against EHV‐1, ataxia grade upon admission, and the development of urinary complications.
Echocardiographic and electrocardiographic findings in Irish Wolfhounds eating high‐pulse or low‐pulse diets
Authors: Coppinger Lily M. , Freeman Lisa M. , Tyrrell William D. , Rosenthal Steven L. , Dentino Mariellen E. , Abrams Frances L. , Rush John E.
Published: April 2024

Background

Apparently healthy dogs of various breeds eating nontraditional, high‐pulse diets can have larger left ventricular diameter, lower systolic function, and more ventricular premature complexes (VPCs) compared with dogs eating traditional, low‐pulse diets. It is unknown whether Irish Wolfhounds eating high‐pulse diets have similar cardiac abnormalities.

Hypothesis/Objectives

To compare electrocardiographic and echocardiographic findings between Irish Wolfhounds eating high‐ or low‐pulse diets.

Animals

Ninety‐seven Irish Wolfhounds.

Methods

Retrospective study of Irish Wolfhounds that had echocardiography performed at dog shows between October 2018 and May 2021. Demographic information, echocardiographic measurements, cardiac rhythm (1‐minute lead II rhythm strip), and main diet were recorded retrospectively. Diets were classified as high‐pulse or low‐pulse based on the presence and location of pulses (peas, lentils, chickpeas, or dry beans) on the ingredient list.

Results

Thirty‐five of 97 Irish Wolfhounds (36%) were eating high‐pulse diets and 62 of 97 (64%) were eating low‐pulse diets. There were no significant differences between diet groups in echocardiographic measurements. A significantly higher percentage of dogs in the high‐pulse diet group (6/35 [17%]) had VPCs compared with those in the low‐pulse diet group (1/62 [2%]; effect size = 0.15 [95% confidence interval: 0.004‐0.31]; P = .005).

Conclusions and Clinical Importance

In this retrospective study of apparently healthy Irish Wolfhounds, high‐pulse diets were associated with a higher prevalence of VPCs which could represent early cardiac abnormalities.
Prognostic potential of copper, zinc, copper/zinc ratio, cobalamin, and serum amyloid A in cats with panleukopenia
Authors: Yanar Kerim Emre , Baysal Sümeyye , Ulaş Nergis , Aktaş Mustafa Sinan , Timurkan Mehmet Özkan , Aydın Hakan
Published: April 2024

Background

Copper (Cu), zinc (Zn), and the copper/zinc ratio (Cu/Zn), which have been studied in gastrointestinal disorders of humans, may facilitate disease prognosis.

Objective

Evaluate the predictive potential of Cu, Zn, cobalamin, and serum amyloid A (SAA) as prognostic indicators in cats with feline panleukopenia (FPV) on admission.

Animals

Client‐owned cats diagnosed with FPV and controls.

Methods

Serum Cu and Zn concentrations were assessed using the spectrophotometric method and serum concentrations of SAA and cobalamin were measured by chemiluminescent immunoassay.

Results

On admission, survivor cats with FPV had significantly higher serum Cu and SAA concentrations and Cu/Zn ratios and significantly lower serum Zn and cobalamin concentrations than controls. Furthermore, non‐survivor cats with FPV had significantly higher serum Cu and SAA concentrations and Cu/Zn ratios and significantly lower cobalamin concentrations than survivors and controls. Prognostic thresholds were calculated, with positive predictive value (PPV) for survival of 90% for Cu (≥120.3 μg/dL), 90% for Cu/Zn (≥1.34), 90% for cobalamin (≤430.4 pg/mL), and 90% for SAA (≥0.85 mg/L).

Conclusions and Clinical Importance

Cu (0.93 area under curve [AUC]), Cu/Zn (0.95 AUC), cobalamin (0.98 AUC), and SAA (0.98 AUC) were excellent biomarkers for predicting prognosis in cats with FPV. Their effectiveness, as assessed by sensitivity (100%), specificity (80%), AUC (0.98), and PPV (90%) from receiver operating characteristic analysis, emphasizes the performance of cobalamin and SAA.
Clinical findings and outcome predictors for multinodular pulmonary fibrosis in horses: 46 cases (2009‐2019)
Authors: Craven Amanda , Todd‐Donato Amy , Stokol Tracy , Liepman Rachel , Glasberg Ilana , Wilkins Pamela , Luethy Daniela , Wong David , Schoster Angelika , van den Brom ‐ Spierenburg Astrid J. , Tomlinson Joy E.
Published: April 2024

Background

Prognostic indicators for equine multinodular pulmonary fibrosis (EMPF), an interstitial fibrosing lung disease, are poorly described.

Hypothesis/Objectives

Describe diagnostic findings and outcome predictors for EMPF.

Animals

Forty‐six adult horses with EMPF.

Methods

Retrospective multicenter case series from 2009 to 2019. Radiographic (n = 27) and ultrasonographic studies (n = 19) from EMPF horses and bronchoalveolar lavage fluid (BALF) cytology from 6 EMPF and 13 asthma cases were independently reviewed and blinded to diagnosis and outcome. Associations between predictor variables and survival were assessed by predictor screening followed by Fisher's exact and Wilcoxon rank sum tests.

Results

Primary clinical findings were weight loss (36/46, 78%), increased respiratory effort (33/46, 72%), tachypnea (32/46, 70%), and fever (18/46, 39%). Macrophage atypia was seen in more EMPF than asthmatic horse BALF (67% vs. 8%; P = .02). Equine herpesvirus 5 (EHV‐5) was detected in 24 of 30 (80%) and hyperfibrinogenemia in 25 of 28 (89%) cases. Twenty‐seven of 46 horses (59%) and 11 of 45 (24%) survived to discharge and to 3 months, respectively. Three‐month survival was associated with lower median (range) respiratory rates (30 [24‐36] vs. 41 [30‐60] breaths per minute; P = .04), and higher BALF lymphocyte:neutrophil ratios (4.7 [1.4‐22] vs. 0.47 [0.11‐1.9]; P = .01) and blood lymphocyte counts (1.25 [0.93‐2.55] vs. 0.90 [0.70‐1.24] × 109/L; P = .03). Imaging findings, EHV‐5 detection, and corticosteroid treatment were not associated with survival.

Conclusions and Clinical Importance

Fever is not a sensitive clinical sign of EMPF. Diagnostic testing should be pursued for horses with increased respiratory rate and effort and weight loss. The prognosis for EMPF horses is poor. Corticosteroid treatment does not improve 3‐month survival.