bluuebunny/crossref_metadata_2025 huggingface dataset:
Complement C1s deficiency in a male Caucasian patient with systemic lupus erythematosus: a case report
Authors: Kleer Jessica S. , Skattum Lillemor , Dubler Denise , Fischer Ingeborg , Zgraggen Armin , Mundwiler Esther , Kim Min Jeong , Trendelenburg Marten
Published: February 2024

Deficiencies of the early complement components of the classical pathway (CP) are well-documented in association with systemic lupus erythematosus (SLE) or SLE-like syndromes and severe pyogenic infections. Among these, complete C1s deficiency has been reported in nine cases so far. Here, we describe a 34-year-old male patient who presented with severe, recurrent infections since childhood, including meningitides with pneumococci and meningococci, erysipelas, subcutaneous abscess, and recurrent infections of the upper airways. The patient also exhibited adult-onset SLE, meeting 7/11 of the ACR criteria and 34 of the 2019 EULAR/ACR classification criteria, along with class IV-G (A) proliferative lupus nephritis (LN). A screening of the complement cascade showed immeasurably low CH50, while the alternative pathway (AP) function was normal. Subsequent determination of complement components revealed undetectable C1s with low levels of C1r and C1q, normal C3, and slightly elevated C4 and C2 concentrations. The patient had no anti-C1q antibodies. Renal biopsy showed class IV-G (A) LN with complement C1q positivity along the glomerular basement membranes (GBMs) and weak deposition of IgG, IgM, and complement C3 and C4 in the mesangium and GBM. In an ELISA-based functional assay determining C4d deposition, the patient’s absent complement activity was fully restored by adding C1s. The genome of the patient was analyzed by whole genome sequencing showing two truncating variants in the C1S gene. One mutation was located at nucleotide 514 in exon 5, caused by a nucleotide substitution from G to T, resulting in a nonsense mutation from Gly172 (p.Gly172*). The other mutation was located at nucleotide 750 in exon 7, where C was replaced by a G, resulting in a nonsense mutation from Tyr250 (p.Tyr250*). Both mutations create a premature stop codon and have not previously been reported in the literature. These genetic findings, combined with the absence of C1s in the circulation, strongly suggest a compound heterozygote C1s deficiency in our patient, without additional defect within the complement cascade. As in a previous C1s deficiency case, the patient responded well to rituximab. The present case highlights unanswered questions regarding the CP’s role in SLE etiopathogenesis.
Neutrophil-derived Activin-A moderates their pro-NETotic activity and attenuates collateral tissue damage caused by Influenza A virus infection
Authors: Divolis Georgios , Synolaki Evgenia , Doulou Athanasia , Gavriil Ariana , Giannouli Christina C. , Apostolidou Anastasia , Foster Martyn L. , Matzuk Martin M. , Skendros Panagiotis , Galani Ioanna-Evdokia , Sideras Paschalis
Published: February 2024

Background

Pre-neutrophils, while developing in the bone marrow, transcribe the Inhba gene and synthesize Activin-A protein, which they store and release at the earliest stage of their activation in the periphery. However, the role of neutrophil-derived Activin-A is not completely understood.

Methods

To address this issue, we developed a neutrophil-specific Activin-A-deficient animal model (S100a8-Cre/Inhbafl/fl mice) and analyzed the immune response to Influenza A virus (IAV) infection. More specifically, evaluation of body weight and lung mechanics, molecular and cellular analyses of bronchoalveolar lavage fluids, flow cytometry and cell sorting of lung cells, as well as histopathological analysis of lung tissues, were performed in PBS-treated and IAV-infected transgenic animals.

Results

We found that neutrophil-specific Activin-A deficiency led to exacerbated pulmonary inflammation and widespread hemorrhagic histopathology in the lungs of IAV-infected animals that was associated with an exuberant production of neutrophil extracellular traps (NETs). Moreover, deletion of the Activin-A receptor ALK4/ACVR1B in neutrophils exacerbated IAV-induced pathology as well, suggesting that neutrophils themselves are potential targets of Activin-A-mediated signaling. The pro-NETotic tendency of Activin-A-deficient neutrophils was further verified in the context of thioglycollate-induced peritonitis, a model characterized by robust peritoneal neutrophilia. Of importance, transcriptome analysis of Activin-A-deficient neutrophils revealed alterations consistent with a predisposition for NET release.

Conclusion

Collectively, our data demonstrate that Activin-A, secreted by neutrophils upon their activation in the periphery, acts as a feedback mechanism to moderate their pro-NETotic tendency and limit the collateral tissue damage caused by neutrophil excess activation during the inflammatory response.
Comparative analysis of swine leukocyte antigen gene diversity in Göttingen Minipigs
Authors: Hammer Sabine E. , Duckova Tereza , Gociman Monica , Groiss Sandra , Pernold Clara P. S. , Hacker Karolin , Kasper Lena , Sprung Julia , Stadler Maria , Jensen Andres Eskjær , Saalmüller Armin , Wenzel Nadine , Figueiredo Constanca
Published: February 2024

Worldwide, pigs represent economically important farm animals, also representing a preferred preclinical large animal model for biomedical studies. The need for swine leukocyte antigen (SLA) typing is increasing with the expanded use of pigs in translational research, infection studies, and for veterinary vaccine design. Göttingen Minipigs (GMP) attract increasing attention as valuable model for pharmacological studies and transplantation research. This study represents a first-time assessment of the SLA gene diversity in Göttingen Minipigs in combination with a comparative metadata analysis with commercial pig lines. As Göttingen Minipigs could harbor private as well as potential novel SLA allele combinations, future research projects would benefit from the characterization of their SLA background. In 209 Göttingen Minipigs, SLA class I (SLA-1, SLA-2, SLA-3) and class II (DRB1, DQB1, DQA) genes were characterized by PCR-based low-resolution (Lr) haplotyping. Criteria and nomenclature used for SLA haplotyping were proposed by the ISAG/IUIS-VIC SLA Nomenclature Committee. Haplotypes were assigned based on the comparison with already known breed or farm-specific allele group combinations. In total, 14 SLA class I and five SLA class II haplotypes were identified in the studied cohort, to manifest in 26 SLA class I but only seven SLA class II genotypes. The most common SLA class I haplotypes Lr-24.0 (SLA-1*15XX or Blank-SLA-3*04:04-SLA-2*06:01~02) and Lr-GMP-3.0 (SLA-1*16:02-SLA-3*03:04-SLA-2*17:01) occurred at frequencies of 23.44 and 18.66%, respectively. For SLA class II, the most prevalent haplotypes Lr-0.21 (DRB1*01XX-DQB1*05XX-DQA*04XX) and Lr-0.03 (DRB1*03:02-DQB1*03:01-DQA*01XX) occurred at frequencies of 38.28 and 30.38%. The comparative metadata analysis revealed that Göttingen Minipigs only share six SLA class I and two SLA class II haplotypes with commercial pig lines. More importantly, despite the limited number of SLA class I haplotypes, the high genotype diversity being observed necessitates pre-experimental SLA background assessment of Göttingen Minipigs in regenerative medicine, allo-transplantation, and xenograft research.
Causal effect of gut microbiota of Defluviitaleaceae on the clinical pathway of “Influenza–Subacute Thyroiditis–Hypothyroidism”
Authors: Zhang Xin , Li Pei-Heng , Wang Dongyue , Li Hancong , Kong Xiangyu , Zhang Gongshuang , Zhao Yue , Liu Jiaye , Wu Wenshuang , Zhang Yuwei , Li Zhi-Hui , Luo Han
Published: February 2024

Introduction

Hypothyroidism has been found to be influenced by gut microbiota. However, it remains unclear which a taxon of gut microbiota plays a key role in this function. Identifying the key bacteria affects hypothyroidism and through what mechanism will be helpful for the prevention of hypothyroidism through specific clinical pathways.

Materials and methods

In Study A, 35 families and 130 genera of gut microbiota are used as exposures, with hypothyroidism as the outcome. The causal effect of the gut microbiota on hypothyroidism is estimated through two-sample Mendelian randomization. Combining the results of the two taxonomical levels, key taxa are selected, which in Study B are investigated for their causal association with multiple generally admitted causes of hypothyroidism and their more upstream factors. For validating and revealing the potential mechanism, enrichment analyses of the related genes and interacting transcription factors were performed.

Results

In Study A, Defluviitaleaceae (OR: 0.043, 95% CI: 0.005–0.363, P = 0.018)/Defluviitaleaceae_UCG_011 (OR: 0.385, 95% CI: 0.172–0.865, P = 0.021) are significantly causally associated with hypothyroidism at both taxonomical levels. In Study B, Defluviitaleaceae family and Defluviitaleaceae_UCG_011 genus show the causal association with decreased thyroiditis (Family: OR: 0.174, 95% CI: 0.046–0.653, P = 0.029; Genus: OR: 0.139, 95% CI: 0.029–0.664, P = 0.043), decreased subacute thyroiditis (Family: OR: 0.028, 95% CI: 0.004–0.213, P = 0.007; Genus: OR: 0.018, 95% CI: 0.002–0.194, P = 0.013), decreased influenza (Family: OR: 0.818, 95% CI: 0.676–0.989, P = 0.038; Genus: OR: 0.792, 95% CI: 0.644–0.974, P = 0.027), and increased anti-influenza H3N2 IgG levels (Family: OR: 1.934, 95% CI: 1.123–3.332, P = 0.017; Genus: OR: 1.675, 95% CI: 0.953–2.943, P = 0.073). The results of the enrichment analysis are consistent with the findings and the suggested possible mechanisms.

Conclusion

Defluviitaleaceae of the gut microbiota displays the probability of causally inhibiting the clinical pathway of “Influenza–Subacute Thyroiditis–Hypothyroidism” and acts as the potential probiotics to prevent influenza, subacute thyroiditis, and hypothyroidism.
Secretory molecules from secretion systems fine-tune the host-beneficial bacteria (PGPRs) interaction
Authors: Gupta Garima , Chauhan Puneet Singh , Jha Prabhat Nath , Verma Rakesh Kumar , Singh Sachidanand , Yadav Virendra Kumar , Sahoo Dipak Kumar , Patel Ashish
Published: February 2024

Numerous bacterial species associate with plants through commensal, mutualistic, or parasitic association, affecting host physiology and health. The mechanism for such association is intricate and involves the secretion of multiple biochemical substances through dedicated protein systems called secretion systems SS. Eleven SS pathways deliver protein factors and enzymes in their immediate environment or host cells, as well as in competing microbial cells in a contact-dependent or independent fashion. These SS are instrumental in competition, initiation of infection, colonization, and establishment of association (positive or negative) with host organisms. The role of SS in infection and pathogenesis has been demonstrated for several phytopathogens, including Agrobacterium, Xanthomonas, Ralstonia, and Pseudomonas. Since there is overlap in mechanisms of establishing association with host plants, several studies have investigated the role of SSs in the interaction of plant and beneficial bacteria, including symbiotic rhizobia and plant growth bacteria (PGPB). Therefore, the present review updates the role of different SSs required for the colonization of beneficial bacteria such as rhizobia, Burkholderia, Pseudomonas, Herbaspirillum, etc., on or inside plants, which can lead to a long-term association. Most SS like T3SS, T4SS, T5SS, and T6SS are required for the antagonistic activity needed to prevent competing microbes, including phytopathogens, ameliorate biotic stress in plants, and produce substances for successful colonization. Others are required for chemotaxis, adherence, niche formation, and suppression of immune response to establish mutualistic association with host plants.
2-Hydroxy-4-methoxybenzaldehyde, a more effective antifungal aroma than vanillin and its derivatives against Fusarium graminearum, destroys cell membranes, inhibits DON biosynthesis, and performs a promising antifungal effect on wheat grains
Authors: Li Qian , Wang Chong , Xiao Hongying , Zhang Yiming , Xie Yanli
Published: February 2024

Fusarium graminearum (F. graminearum) is a severe pathogen threatening the safety of agriculture and food. This study aimed to explore the antifungal efficacies of several plant-derived natural compounds (vanillin and its derivatives) against the growth of F. graminearum and investigate the antifungal mechanism of 2-hydroxy-4-methoxybenzaldehyde (HMB), the strongest one. The minimum inhibitory concentration (MIC) of HMB in inhibiting mycelial growth was 200 μg/mL. HMB at MIC damaged cell membranes by increasing the permeability by about 6-fold (p < 0.05) as evidenced by propidium iodide (PI) staining. Meanwhile, the content of malondialdehyde (MDA) and glycerol was increased by 45.91 and 576.19% by HMB treatment at MIC, respectively, indicating that lipid oxidation and osmotic stress occurred in the cell membrane. Furthermore, HMB exerted a strong antitoxigenic role as the content of deoxynivalenol (DON) was remarkably reduced by 93.59% at MIC on 7th day. At last, the antifungal effect of HMB against F. graminearum was also confirmed on wheat grains. These results not only revealed the antifungal mechanism of HMB but also suggested that HMB could be applied as a promising antifungal agent in the preservation of agricultural products.
Probing RNA structural landscapes across Candida yeast genomes
Authors: Chorostecki Uciel , Saus Ester , Gabaldón Toni
Published: February 2024

Understanding the intricate roles of RNA molecules in virulence and host-pathogen interactions can provide valuable insights into combatting infections and improving human health. Although much progress has been achieved in understanding transcriptional regulation during host-pathogen interactions in diverse species, more is needed to know about the structure of pathogen RNAs. This is particularly true for fungal pathogens, including pathogenic yeasts of the Candida genus, which are the leading cause of hospital-acquired fungal infections. Our work addresses the gap between RNA structure and their biology by employing genome-wide structure probing to comprehensively explore the structural landscape of mRNAs and long non-coding RNAs (lncRNAs) in the four major Candida pathogens. Specifically focusing on mRNA, we observe a robust correlation between sequence conservation and structural characteristics in orthologous transcripts, significantly when sequence identity exceeds 50%, highlighting structural feature conservation among closely related species. We investigate the impact of single nucleotide polymorphisms (SNPs) on mRNA secondary structure. SNPs within 5′ untranslated regions (UTRs) tend to occur in less structured positions, suggesting structural constraints influencing transcript regulation. Furthermore, we compare the structural properties of coding regions and UTRs, noting that coding regions are generally more structured than UTRs, consistent with similar trends in other species. Additionally, we provide the first experimental characterization of lncRNA structures in Candida species. Most lncRNAs form independent subdomains, similar to human lncRNAs. Notably, we identify hairpin-like structures in lncRNAs, a feature known to be functionally significant. Comparing hairpin prevalence between lncRNAs and protein-coding genes, we find enrichment in lncRNAs across Candida species, humans, and Arabidopsis thaliana, suggesting a conserved role for these structures. In summary, our study offers valuable insights into the interplay between RNA sequence, structure, and function in Candida pathogens, with implications for gene expression regulation and potential therapeutic strategies against Candida infections.
Serpin peptidase inhibitor, clade E, member 2 in physiology and pathology: recent advancements
Authors: Wu Shutong , Yang Yuchao , Zhang Meiling , Khan Asmat Ullah , Dai Jingxing , Ouyang Jun
Published: February 2024

Serine protease inhibitors (serpins) are the most numerous and widespread multifunctional protease inhibitor superfamily and are expressed by all eukaryotes. Serpin E2 (serpin peptidase inhibitor, clade E, member 2), a member of the serine protease inhibitor superfamily is a potent endogenous thrombin inhibitor, mainly found in the extracellular matrix and platelets, and expressed in numerous organs and secreted by many cell types. The multiple functions of serpin E2 are mainly mediated through regulating urokinase-type plasminogen activator (uPA, also known as PLAU), tissue-type plasminogen activator (tPA, also known as PLAT), and matrix metalloproteinase activity, and include hemostasis, cell adhesion, and promotion of tumor metastasis. The importance serpin E2 is clear from its involvement in numerous physiological and pathological processes. In this review, we summarize the structural characteristics of the Serpin E2 gene and protein, as well as its roles physiology and disease.
Comparative analysis of multimodal biomarkers for amyloid-beta positivity detection in Alzheimer's disease cohorts
Authors: Mehdipour Ghazi Mostafa , Selnes Per , Timón-Reina Santiago , Tecelão Sandra , Ingala Silvia , Bjørnerud Atle , Kirsebom Bjørn-Eivind , Fladby Tormod , Nielsen Mads
Published: February 2024

Introduction

Efforts to develop cost-effective approaches for detecting amyloid pathology in Alzheimer's disease (AD) have gained significant momentum with a focus on biomarker classification. Recent research has explored non-invasive and readily accessible biomarkers, including magnetic resonance imaging (MRI) biomarkers and some AD risk factors.

Methods

In this comprehensive study, we leveraged a diverse dataset, encompassing participants with varying cognitive statuses from multiple sources, including cohorts from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and our in-house Dementia Disease Initiation (DDI) cohort. As brain amyloid plaques have been proposed as sufficient for AD diagnosis, our primary aim was to assess the effectiveness of multimodal biomarkers in identifying amyloid plaques, using deep machine learning methodologies.

Results

Our findings underscore the robustness of the utilized methods in detecting amyloid beta positivity across multiple cohorts. Additionally, we investigated the potential of demographic data to enhance MRI-based amyloid detection. Notably, the inclusion of demographic risk factors significantly improved our models' ability to detect amyloid-beta positivity, particularly in early-stage cases, exemplified by an average area under the ROC curve of 0.836 in the unimpaired DDI cohort.

Discussion

These promising, non-invasive, and cost-effective predictors of MRI biomarkers and demographic variables hold the potential for further refinement through considerations like APOE genotype and plasma markers.
Inhibition of corticosterone synthesis impairs cued water maze consolidation, but it does not affect the expression of BDNF, CK2 and SGK1 genes in dorsal striatum
Authors: Pegueros-Maldonado Rogelio , Pech-Pool Santiago M. , Blancas Jaisson J. , Prado-Alcalá Roberto A. , Arámburo Carlos , Luna Maricela , Quirarte Gina L.
Published: February 2024

Corticosterone (CORT) release during learning experiences is associated with strong memories and activity of the glucocorticoid receptor. It has been shown that lesions of the dorsal striatum (DS) of rats trained in the cued version of the Morris water maze impair memory, and that local injection of CORT improves its performance, suggesting that DS activity is involved in procedural memory which may be modulated by CORT. We trained rats in cued Morris water maze and analyzed the effect of CORT synthesis inhibition on performance, CORT levels, expression of plasticity-involved genes, such as the brain derived neurotrophic factor (BDNF), casein kinase 2 (CK2), and the serum/glucocorticoid regulated kinase 1 (SGK1), as well as the presence of phosphorylated nuclear glucocorticoid receptor in serine 232 (pGR-S232) in the DS. The inhibition of CORT synthesis by metyrapone reduced CORT levels in plasma, prevented its increment in DS and impaired the performance of cued water maze. Additionally, there was an increase of CK2 and SGK1 mRNAs expression in trained subjects, which was unrelated to CORT levels. Finally, we did not observe changes in nuclear pGR-S232 in any condition. Our findings agree with evidence demonstrating that decreasing CORT levels hinders acquisition and consolidation of the spatial version of the Morris water maze; these novel findings broaden our knowledge about the involvement of the DS in the mechanisms underlying procedural memory.
Proteasome localization and activity in pig brain and in vivo small molecule screening for activators
Authors: Amrein Almira Adriana , Chen May W. , El Demerdash Nagat , Javdan Cameron , Park Dongseok , Lee Jennifer K. , Martin Lee J.
Published: February 2024

Introduction

Loss of proteasome function, proteinopathy, and proteotoxicity may cause neurodegeneration across the human lifespan in several forms of brain injury and disease. Drugs that activate brain proteasomes in vivo could thus have a broad therapeutic impact in neurology.

Methods

Using pigs, a clinically relevant large animal with a functionally compartmental gyrencephalic cerebral cortex, we evaluated the localization and biochemical activity of brain proteasomes and tested the ability of small molecules to activate brain proteasomes.

Results

By Western blotting, proteasome protein subunit PSMB5 and PSMA3 levels were similar in different pig brain regions. Immunohistochemistry for PSMB5 showed localization in the cytoplasm (diffuse and particulate) and nucleus (cytoplasm < nucleus). Some PSMB5 immunoreactivity was colocalized with mitochondrial (voltage-gated anion channel and cyclophilin D) and cell death (Aven) proteins in the neuronal soma and neuropil in the neocortex of pig and human brains. In the nucleus, PSMB5 immunoreactivity was diffuse, particulate, and clustered, including perinucleolar decorations. By fluorogenic assay, proteasome chymotrypsin-like activities (CTL) in crude tissue soluble fractions were generally similar within eight different pig brain regions. Proteasome CTL activity in the hippocampus was correlated with activity in nasal mucosa biopsies. In pilot analyses of subcellular fractions of pig cerebral cortex, proteasome CTL activity was highest in the cytosol and then ~50% lower in nuclear fractions; ~15–20% of total CTL activity was in pure mitochondrial fractions. With in-gel activity assay, 26S-singly and -doubly capped proteasomes were the dominant forms in the pig cerebral cortex. With a novel in situ histochemical activity assay, MG132-inhibitable proteasome CTL activity was localized to the neuropil, as a mosaic, and to cell bodies, nuclei, and centrosome-like perinuclear satellites. In piglets treated intravenously with pyrazolone derivative and chlorpromazine over 24 h, brain proteasome CTL activity was modestly increased.

Discussion

This study shows that the proteasome in the pig brain has relative regional uniformity, prominent nuclear and perinuclear presence with catalytic activity, a mitochondrial association with activity, 26S-single cap dominance, and indications from small molecule systemic administration of pyrazolone derivative and chlorpromazine that brain proteasome function appears safely activable.
Spasticity-Plus syndrome in multiple sclerosis patients in a tertiary hospital in Spain
Authors: Goicochea Briceño Haydee , Higueras Yolanda , Ruiz Pérez Irene , García Domínguez José Manuel , Cuello Juan Pablo , Meldaña Rivera Ariana , Martínez Ginés María Luisa
Published: February 2024

Introduction

Spasticity is a common symptom in multiple sclerosis (MS) and it is often associated with other symptoms such as spasms/cramps and pain. The concept of Spasticity-Plus syndrome takes into account that spasticity is accompanied by one or more symptoms (spasms/cramps, pain, bladder dysfunction, sleep disorders, fatigue and/or tremor). As these symptoms share a common cannabinoid control, therapy acting on cannabinoid receptors may be useful. The main study objectives were to determine the number of MS patients who met Spasticity-Plus syndrome criteria and to identify the most common symptoms.

Methods

Clinical records of MS patients treated with nabiximols in a tertiary hospital from 2002 to 2022 were reviewed retrospectively.

Results

Of the 73 patients included in the study, 53.4% were women, and most had secondary progressive MS (64.4%). All patients met the criteria for Spasticity-Plus syndrome: 100% had spasticity and at least another symptom. Pain was the second most common symptom (91.8%), followed by spasms/cramps (79.4%), and fatigue (76.7%). Sleep disturbances (p < 0.0001) and tremor (p < 0.027) were more frequent in patients with relapsing–remitting MS than in patients with progressive MS. No statistically significant differences were found for spasticity, pain, spasms/cramps, and fatigue between MS phenotypes. Regarding symptoms clusters, 94.4% of the patients had three or more symptoms. Spasticity was more frequently associated with pain (91.8%) and spasms/cramps (79.4%).

Conclusion

Spasticity-Plus syndrome was present in all the study population of patients with different MS phenotypes, and treated with nabiximols.
A method for synchronized use of EEG and eye tracking in fully immersive VR
Authors: Larsen Olav F. P. , Tresselt William G. , Lorenz Emanuel A. , Holt Tomas , Sandstrak Grethe , Hansen Tor I. , Su Xiaomeng , Holt Alexander
Published: February 2024

This study explores the synchronization of multimodal physiological data streams, in particular, the integration of electroencephalography (EEG) with a virtual reality (VR) headset featuring eye-tracking capabilities. A potential use case for the synchronized data streams is demonstrated by implementing a hybrid steady-state visually evoked potential (SSVEP) based brain-computer interface (BCI) speller within a fully immersive VR environment. The hardware latency analysis reveals an average offset of 36 ms between EEG and eye-tracking data streams and a mean jitter of 5.76 ms. The study further presents a proof of concept brain-computer interface (BCI) speller in VR, showcasing its potential for real-world applications. The findings highlight the feasibility of combining commercial EEG and VR technologies for neuroscientific research and open new avenues for studying brain activity in ecologically valid VR environments. Future research could focus on refining the synchronization methods and exploring applications in various contexts, such as learning and social interactions.
Growth patterns of preterm and small for gestational age children during the first 10 years of life
Authors: Nguyen Phuong Thi , Nguyen Phuong Hong , Tran Lan Mai , Khuong Long Quynh , Nguyen Son Van , Young Melissa F. , Ramakrishnan Usha
Published: February 2024

Background

Preterm and small for gestational age (SGA) remain significant public health concerns worldwide. Yet limited evidence exists on their growth patterns during childhood from low-or middle-income countries.

Objectives

We investigated the postnatal growth patterns of preterm and SGA compared to term appropriate for gestational age (AGA) children from birth to 10–11y, and examined the impact of birth status on child nutritional status during the school age years.

Methods

Children born to women who participated in a double-blinded randomized controlled trial of preconception micronutrient supplementation in Vietnam were classified into three groups: preterm AGA (n = 130), full-term SGA (n = 165) and full-term AGA (n = 1,072). Anthropometric data (weight and height) were collected prospectively at birth, 3, 6, 12, 18, 24 months and at 6–7 and 10–11y. We used ANOVA and multiple regression models to examine the differences in growth patterns from birth to 10–11y as well as child undernutrition and overnutrition by birth status.

Results

Children who were born preterm exhibited rapid postnatal growth, but still had lower HAZ at 1y and 2y and showed catch up to the AGA group at 6y. Compared to those born AGA, SGA infants had higher risk of thinness (BMIZ < −2) at 2y and 6y (adjusted Odds Ratio, AOR [95% CI] 2.5 [1.0, 6.1] and 2.6 [1.4, 4.6], respectively); this risk reduced at 10–11y (1.6 [0.9, 2.8]). The risk of stunting (HAZ < −2) was also 2.4 [1.5, 3.8] and 2.3 times [1.2, 4.1] higher in SGA than AGA group at ages 2y and 6–7y, respectively, with no differences at 10y. Although preterm children had higher rates of thinness and stunting at 2y compared to AGA children, these differences were not statistically significant. No associations were found between preterm or SGA and overweight /obesity at age 10–11y.

Conclusion

Children who were born term-SGA continued to demonstrate deficits in weight and height during childhood whereas those born preterm showed catch-up growth by age 6–7y. Additional efforts to reduce the burden of these conditions are needed, particularly during school-age and early adolescents when children are exposed to challenging environments and have higher demands for nutrition.
Oncopig bladder cancer cells recapitulate human bladder cancer treatment responses in vitro
Authors: Segatto Natália V. , Simões Lucas D. , Bender Camila B. , Sousa Fernanda S. , Oliveira Thais L. , Paschoal Júlia D. F. , Pacheco Bruna S. , Lopes Isadora , Seixas Fabiana K. , Qazi Aisha , Thomas Faith M. , Chaki Sulalita , Robertson Noah , Newsom Jordan , Patel Shovik , Rund Laurie A. , Jordan Luke R. , Bolt Courtni , Schachtschneider Kyle M. , Schook Lawrence B. , Collares Tiago V.
Published: February 2024

Introduction

Bladder cancer is a common neoplasia of the urinary tract that holds the highest cost of lifelong treatment per patient, highlighting the need for a continuous search for new therapies for the disease. Current bladder cancer models are either imperfect in their ability to translate results to clinical practice (mouse models), or rare and not inducible (canine models). Swine models are an attractive alternative to model the disease due to their similarities with humans on several levels. The Oncopig Cancer Model has been shown to develop tumors that closely resemble human tumors. However, urothelial carcinoma has not yet been studied in this platform.

Methods

We aimed to develop novel Oncopig bladder cancer cell line (BCCL) and investigate whether these urothelial swine cells mimic human bladder cancer cell line (5637 and T24) treatment-responses to cisplatin, doxorubicin, and gemcitabine in vitro.

Results

Results demonstrated consistent treatment responses between Oncopig and human cells in most concentrations tested (p>0.05). Overall, Oncopig cells were more predictive of T24 than 5637 cell therapeutic responses. Microarray analysis also demonstrated similar alterations in expression of apoptotic (GADD45B and TP53INP1) and cytoskeleton-related genes (ZMYM6 and RND1) following gemcitabine exposure between 5637 (human) and Oncopig BCCL cells, indicating apoptosis may be triggered through similar signaling pathways. Molecular docking results indicated that swine and humans had similar Dg values between the chemotherapeutics and their target proteins.

Discussion

Taken together, these results suggest the Oncopig could be an attractive animal to model urothelial carcinoma due to similarities in in vitro therapeutic responses compared to human cells.
Current therapies and progress in the treatment of advanced gastric cancer
Authors: Li Hongyu , Shen Ming , Wang Shihao
Published: February 2024

Gastric cancer (GC) remains one of the most life-threatening disease worldwide with poor prognosis because of the absence of effective treatment and the delay in diagnosis. Due to the delay of diagnosis, a large proportion of GC patients are diagnosed as advanced GC, with extreme short lifespan. In the past few years, some pivotal progress and novel therapies was proposed, and conducted into clinical researches and practice. In this study, we summarized the development of several novel immunotherapy or targeted treatment modalities for advanced GC, including immune checkpoint inhibitors, anti-angiogenic therapy and cancer vaccines. Additionally, the advantage and potential weakness in each of these therapeutic methods are also listed. Finally, we discussed the promising research direction of advanced GC treatment, and the limitation in basic and clinical research of advanced GC, including the combination of immunotherapy and targeted therapy.
Sleep disorders and cancer incidence: examining duration and severity of diagnosis among veterans
Authors: Burch James B. , Delage Alexandria F. , Zhang Hongmei , McLain Alexander C. , Ray Meredith A. , Miller Austin , Adams Swann A. , Hébert James R.
Published: February 2024

Introduction

Sleep disruption affects biological processes that facilitate carcinogenesis. This retrospective cohort study used de-identified data from the Veterans Administration (VA) electronic medical record system to test the hypothesis that patients with diagnosed sleep disorders had an increased risk of prostate, breast, colorectal, or other cancers (1999-2010, N=663,869). This study builds upon existing evidence by examining whether patients with more severe or longer-duration diagnoses were at a greater risk of these cancers relative to those with a less severe or shorter duration sleep disorder.

Methods

Incident cancer cases were identified in the VA Tumor Registry and sleep disorders were defined by International Classification of Sleep Disorder codes. Analyses were performed using extended Cox regression with sleep disorder diagnosis as a time-varying covariate.

Results

Sleep disorders were present among 56,055 eligible patients (8% of the study population); sleep apnea (46%) and insomnia (40%) were the most common diagnoses. There were 18,181 cancer diagnoses (41% prostate, 12% colorectal, 1% female breast, 46% other). The hazard ratio (HR) for a cancer diagnosis was 1.45 (95% confidence interval [CI]: 1.37, 1.54) among those with any sleep disorder, after adjustment for age, sex, state of residence, and marital status. Risks increased with increasing sleep disorder duration (short [<1-2 years] HR: 1.04 [CI: 1.03-1.06], medium [>2-5 years] 1.23 [1.16-1.32]; long [>5-12 years] 1.52 [1.34-1.73]). Risks also increased with increasing sleep disorder severity using cumulative sleep disorder treatments as a surrogate exposure; African Americans with more severe disorders had greater risks relative to those with fewer treatments and other race groups. Results among patients with only sleep apnea, insomnia, or another sleep disorder were similar to those for all sleep disorders combined.

Discussion

The findings are consistent with other studies indicating that sleep disruption is a cancer risk factor. Optimal sleep and appropriate sleep disorder management are modifiable risk factors that may facilitate cancer prevention.
Solid pseudopapillary neoplasm of the pancreas: a retrospective study of 195 cases
Authors: Fu Chang , Li Xiaocong , Wang Yongxin , Wang Chuangshi , Jin Hengwei , Liu Kai , Xu Hongji
Published: February 2024

Objective

Solid pseudopapillary neoplasm of the pancreas (SPN) is a rare exocrine tumor of the pancreas. The aim of our study is to summarize the clinical features of SPN and to analyze the risk factors for malignant SPN.

Methods

From May 2013 to September 2022, patients who were pathologically confirmed to have SPN were retrospectively reviewed. Demographic data, clinical and pathological features, follow-up data were collected and analyzed. To investigate the factors influencing the benign or malignant nature of SPN, we employed logistic regression. Additionally, we utilized Kaplan-Meier curves to depict and analyze the overall prognosis.

Results

A total of 195 patients were included, 163 of whom were female and the average age of all patients was 31.7 years old. Among 195 patients, 101 patients (51.8%) had no obvious clinical symptoms and their pancreatic lesions were detected during routine examination. The primary symptom was abdominal pain and distension in 64 cases (32.8%). The maximum diameter of SPN tumors ranged from 1-17 cm (mean 6.19 cm). Forty-eight postoperative complications developed in 43 (22.1%) patients. After a median follow-up duration of 44.5 months, the overall 5-year survival rate was 98.8% and the recurrence rate was 1.5%. Furthermore, we observed a statistically significant difference in the completeness of the tumor capsule between benign and malignant SPN.

Conclusion

SPN is associated with a favorable long-term survival after surgery in our large sample size cohort. For malignant SPN, tumor capsule incompleteness is an independent risk factor.
Case report: A case of hyperthyroidism secondary to bone metastasis of differentiated thyroid cancer
Authors: Gu Tingyu , Zhao Zhihong , Shi Yuanyuan , Sun Zhenhua , Wang Yao , He Zhiyuan , Wang Kun
Published: February 2024

It is usually believed that differentiated thyroid cancer is less likely to have distant metastases and rarely occurs secondary to hyperthyroidism. In our case report, we describe a patient diagnosed with thyroid fetal adenoma in 2002 who subsequently presented with a painful lump in her right rib. Through puncture biopsy, the mass was considered as metastatic follicular thyroid carcinoma, and then she appeared to have hyperthyroidism. The results of SPECT examination and other tests suggested that the hyperthyroidism was secondary to the thyroid cancer. The patient further underwent total thyroidectomy, and the pathology did not find any follicular thyroid foci. In this article, we analyze and discuss this case and review the relevant literature.
In vitro and in vivo modeling systems of supratentorial ependymomas
Authors: Hatanaka Emily A. , Breunig Joshua J.
Published: February 2024

Ependymomas are rare brain tumors that can occur in both children and adults. Subdivided by the tumors’ initial location, ependymomas develop in the central nervous system in the supratentorial or infratentorial/posterior fossa region, or the spinal cord. Supratentorial ependymomas (ST-EPNs) are predominantly characterized by common driver gene fusions such as ZFTA and YAP1 fusions. Some variants of ST-EPNs carry a high overall survival rate. In poorly responding ST-EPN variants, high levels of inter- and intratumoral heterogeneity, limited therapeutic strategies, and tumor recurrence are among the reasons for poor patient outcomes with other ST-EPN subtypes. Thus, modeling these molecular profiles is key in further studying tumorigenesis. Due to the scarcity of patient samples, the development of preclinical in vitro and in vivo models that recapitulate patient tumors is imperative when testing therapeutic approaches for this rare cancer. In this review, we will survey ST-EPN modeling systems, addressing the strengths and limitations, application for therapeutic targeting, and current literature findings.
Assessing long-term, vestibulotoxic side effects after gentamicin therapy in neonatal sepsis or infection using video head impulse test
Authors: Zaubitzer Lena , Kotzur Anja , Hegemann Stefan , Rotter Nicole , Schell Angela
Published: February 2024

Study background

Newborn infection and sepsis remain serious problems. Guideline-compliant therapy includes, among other therapeutics, calculated intravenous antibiosis with gentamicin. One of the known side effects of gentamicin is severe vestibulotoxicity, which can be detected using the video head impulse test (VHIT), which is a sensitive examination method for the detection of vestibular hypofunction in children and adults. Previous studies on the vestibulotoxicity of gentamicin in newborns were carried out using caloric testing, rotary testing, and electronystagmography. Nevertheless, there are currently no data available on VHIT examinations in children who have been treated with neonatal gentamicin therapy.

Methods

A single-center, prospective cross-sectional study, was conducted at a tertial referral center. VHIT was performed on 23 children aged 3–7 years who had received intravenous gentamicin therapy for at least five days as part of the treatment of newborn sepsis between 2012 and 2016. Main outcome was median gain and occurrence of refixational saccades as measured with VHIT. In addition, the children's parents received questionnaires to detect possible risk factors and vestibular and cochlear abnormalities.

Results

Out of 23 children with a mean age of four years and seven months (ranging from 3 to 7 years), 11 (47.8%) indicated abnormal results in VHIT. The VHIT results were unilaterally abnormal in six children (26.1%) and bilaterally abnormal in five others (21.7%). Additionally, five of the children with an abnormal HIT had abnormalities, as found in the questionnaire results.

Conclusion

and Relevance: Almost half of the children observed after having undergone gentamicin therapy as newborns showed abnormalities in VHIT, although they did not show any clinical signs of disbalance or vestibular hypofunction. VHIT can serve as a sensitive investigation method for the early screening of post-therapeutic vestibulotoxic side effects after gentamicin therapy in children. Additionally, VHIT can enable early intervention in these children.
Effects of accumulated exercise on the stiffness and hemodynamics of the common carotid artery
Authors: Liu Haibin , Shen Bingyi , Li Zusheng , Xue Chundong , Zhao Hongling , Pan Xin , Xu Dong
Published: February 2024

Purpose: This research aims to study and compare the effects of moderate-intensity continuous exercise and accumulated exercise with different number of bouts on common carotid arterial stiffness and hemodynamic variables.

Methods: Thirty healthy male adults were recruited to complete four trials in a randomized crossover design: no-exercise (CON); continuous exercise (CE, 30-min cycling); accumulated exercise including two or three bouts with 10-min rest intervals (AE15, 2 × 15-min cycling; AE10, 3 × 10-min cycling). The intensity in all the exercise trials was set at 45%–55% heart rate reserve. Blood pressure, right common carotid artery center-line velocity, and arterial inner diameter waveforms were measured at baseline and immediately after exercise (0 min), 10 min, and 20 min.

Results: 1) The arterial stiffness index and pressure–strain elastic modulus of the CE and AE15 groups increased significantly at 0 min, arterial diameters decreased in AE15 and AE10, and all indicators recovered at 10 min. 2) The mean blood flow rate and carotid artery center-line velocity increased in all trials at 0 min, and only the mean blood flow rate of AE10 did not recover at 10 min. 3) At 0 min, the blood pressure in all trials was found to be increased, and the wall shear stress and oscillatory shear index of AE10 were different from those in CE and AE15. At 20 min, the blood pressure of AE10 significantly decreased, and the dynamic resistance, pulsatility index, and peripheral resistance of CE partially recovered.

Conclusion: There is no significant difference in the acute effects of continuous exercise and accumulated exercise on the arterial stiffness and diameter of the carotid artery. Compared with continuous exercise, accumulated exercise with an increased number of bouts is more effective in increasing cerebral blood supply and blood pressure regulation, and its oscillatory shear index recovers faster. However, the improvement of blood flow resistance in continuous exercise was better than that in accumulated exercise.
Green manure incorporation enhanced soil labile phosphorus and fruit tree growth
Authors: Yang Yuanyu , Zhang Jianwei , Chang Xia , Chen Lunlun , Liu Yongmin , Xu Qingwei , Wang Mengjuan , Yu Haiyan , Huang Renmei , Zhang Jie , Hu Yingxiao , Hu Qijuan , Shi Xiaojun , Zhang Yuting
Published: February 2024

Introduction

The incorporation of green manures substantially enhances the conversion of external phosphorus (P) fertilizers and soil-reserved P into forms readily available to plants. The study aims to evaluate the influence of green manure additions on soil phosphorus dynamics and citrus growth, considering different green manure species and initial soil phosphorus levels. Additionally, the research seeks to elucidate the microbiological mechanisms underlying the observed effects.

Methods

A citrus pot experiment was conducted under both P-surplus (1.50 g·P·kg-1) and P-deficient (0.17 g·P·kg-1) soils with incorporating legume (Leg), non-legume (Non-Leg) or no green manure residues (CK), and 18O-P labeled KH2PO4 (0.5 g, containing 80‰ δ18Op) was additionally introduced to trace the turnover characteristics of chemical P fertilizer mediated by soil microorganisms.

Results and discussion

In P-surplus soil, compared with the CK treatment, the Leg treatment significantly increased soil H2O-Pi (13.6%), NaHCO3-Po (8.9%), NaOH-Pi (9.5%) and NaOH-Po (30.0%) content. It also promoted rapid turnover of P sources into H2O-Pi and NaHCO3-Pi pools by enhancing the phoC (576.6%) gene abundance. In contrast, the Non-Leg treatment significantly augmented soil H2O-Pi (9.2%) and NaHCO3-Po (8.5%) content, facilitating the turnover of P sources into NaHCO3-Pi pools. Under P-deficient soil conditions, compared with the CK treatment, the Leg treatment notably raised soil H2O-Pi (150.0%), NaHCO3-Pi (66.3%), NaHCO3-Po (34.8%) and NaOH-Pi (59.0%) content, contributing to the transfer of P sources into NaHCO3-Pi and NaOH-Pi pools. This effect was achieved through elevated ALP (33.8%) and ACP (12.9%) activities and increased pqqC (48.1%), phoC (42.9%), phoD (21.7%), and bpp (27.4%) gene abundances. The Non-Leg treatment, on the other hand, led to significant increases in soil NaHCO3-Pi (299.0%) and NaHCO3-Po (132.6%) content, thereby facilitating the turnover of P sources into NaHCO3-Pi and NaOH-Pi pools, except for the phoC gene abundance. Both Leg and Non-Leg treatments significantly improved citrus growth (7.3-20.0%) and P uptake (15.4-42.1%) in P-deficient soil but yielded no substantial effects in P-surplus soil. In summary, introducing green manure crops, particularly legume green manure, emerges as a valuable approach to enhance soil P availability and foster fruit tree growth in orchard production.
Positive time use: a missing link between time perspective, time management, and well-being
Authors: Osin Evgeny , Boniwell Ilona
Published: February 2024

Introduction

The notion of satisfaction with the use of one’s time has not been operationalized previously. Based on qualitative interviews, we propose a concept of positive time use comprised by four components: self-congruence of daily activities, balance between activities, efficient use of time, and a sense of mastery over one’s time.

Methods

Using data from two UK adult samples (N = 173 and N = 357), we developed a new measure, Positive Time Use Inventory (PTUI), and investigated its structural and convergent validity.

Results and discussion

The associations of positive time use with balanced time perspective, affect balance, satisfaction with life, sense of coherence, and self-reported satisfaction with time use indicate convergent and discriminant validity of the new measure. Positive time use partially explained the associations of balanced time perspective with subjective well-being and fully mediated the effects of future time perspective and time management on subjective well-being. We propose positive time use as a new model of temporal well-being, which brings together the notions of work-life balance, time efficiency, and time mastery in a single comprehensive framework, helping to inform the time management coaching interventions.