bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatitis B surface antigen positivity is associated with poor short- and long-term outcomes in patients with diffuse large B-cell lymphoma who received CHOP or R-CHOP
Authors: Zhan Zhumei , Guo Wei , Wan Xin , Wang Bowen , Li Jia , Wang Haotian , Li Zhe , Huang Yuhua , Young Ken H. , Bai Ou
Published: January 2024

Objective

The development of diffuse large B-cell lymphoma (DLBCL) is closely related to the host infection status. China is a highly endemic area for hepatitis B virus (HBV) infection. It is not clear whether HBV infection has a consistent effect on the prognostic implications of patients with DLBCL in different treatment settings.

Materials and methods

We conducted a cohort study of 692 patients with DLBCL receiving three or more cycles of treatment with a CHOP or R-CHOP regimen from the First Hospital of Jilin University between July 2011 and July 2022. The patients were divided into two groups based on their hepatitis B surface antigen (HBsAg) status: HBsAg-positive (n = 84, 12.1%) and HBsAg-negative (n = 608, 87.9%) groups. Tumor specimens from 180 patients with primary DLBCL were collected for next-generation sequencing (NGS).

Results

The HBsAg-positive group had more frequent abnormal liver function (P = 0.003), hypoalbuminemia (P < 0.001), incidence of > 2 extranodal organs (P = 0.011), and spleen involvement (P < 0.001) than the HBsAg-negative group. HBsAg-positive patients had lower complete response (CR) and overall response rates (ORR) rates (all the p values < 0.05), in either the CHOP group or R-CHOP group. Among patients receiving R-CHOP, the rates of disease progression within 12 and 24 months were higher in the HBsAg-positive group than in the HBsAg-negative group (P=0.018, P=0.029). However, no significant difference in disease progression was observed between HBsAg-positive and HBsAg-negative patients in the CHOP group(P > 0.05). HBsAg positivity (OS: HR [95% CI] = 2.511 [1.214-5.192], P = 0.013) was only associated with poorer OS in the CHOP group. Whereas in the R-CHOP group, HBsAg positivity was associated with both poorer OS and PFS (OS: HR [95% CI] = 1.672 [1.050-2.665], P = 0.030; PFS: HR [95% CI] = 1.536 [1.013-2.331], P = 0.043). Additionally, HBsAg-positive patients with DLBCL also had a higher prevalence of mutations in MYC, ATM, PTPN6, and epigenetically regulated genes.

Conclusion

These findings suggest that HBsAg-positive DLBCL patients may represent a distinct subgroup with a poorer prognosis. The standard therapies may be insufficient and new therapeutic strategies should be developed based on a better understanding of the underlying mechanisms of chemoresistance.
Early allogeneic immune modulation after establishment of donor hematopoietic cell-induced mixed chimerism in a nonhuman primate kidney transplant model
Authors: Little Christopher J. , Kim Steven C. , Fechner John H. , Post Jen , Coonen Jennifer , Chlebeck Peter , Winslow Max , Kobuzi Dennis , Strober Samuel , Kaufman Dixon B.
Published: January 2024

Background

Mixed lymphohematopoietic chimerism is a proven strategy for achieving operational transplant tolerance, though the underlying immunologic mechanisms are incompletely understood.

Methods

A post-transplant, non-myeloablative, tomotherapy-based total lymphoid (TLI) irradiation protocol combined with anti-thymocyte globulin and T cell co-stimulatory blockade (belatacept) induction was applied to a 3-5 MHC antigen mismatched rhesus macaque kidney and hematopoietic cell transplant model. Mechanistic investigations of early (60 days post-transplant) allogeneic immune modulation induced by mixed chimerism were conducted.

Results

Chimeric animals demonstrated expansion of circulating and graft-infiltrating CD4+CD25+Foxp3+ regulatory T cells (Tregs), as well as increased differentiation of allo-protective CD8+ T cell phenotypes compared to naïve and non-chimeric animals. In vitro mixed lymphocyte reaction (MLR) responses and donor-specific antibody production were suppressed in animals with mixed chimerism. PD-1 upregulation was observed among CD8+ T effector memory (CD28-CD95+) subsets in chimeric hosts only. PD-1 blockade in donor-specific functional assays augmented MLR and cytotoxic responses and was associated with increased intracellular granzyme B and extracellular IFN-γ production.

Conclusions

These studies demonstrated that donor immune cell engraftment was associated with early immunomodulation via mechanisms of homeostatic expansion of Tregs and early PD-1 upregulation among CD8+ T effector memory cells. These responses may contribute to TLI-based mixed chimerism-induced allogenic tolerance.
Cryptosporidium parvum infection alters the intestinal mucosa transcriptome in neonatal calves: implications for immune function
Authors: Veshkini Arash , Dengler Franziska , Bachmann Lisa , Liermann Wendy , Helm Christiane , Ulrich Reiner , Delling Cora , Kühn Christa , Hammon Harald M.
Published: January 2024

One of the leading causes of infectious diarrhea in newborn calves is the apicomplexan protozoan Cryptosporidium parvum (C. parvum). However, little is known about its immunopathogenesis. Using next generation sequencing, this study investigated the immune transcriptional response to C. parvum infection in neonatal calves. Neonatal male Holstein-Friesian calves were either orally infected (N = 5) or not (CTRL group, N = 5) with C. parvum oocysts (gp60 subtype IIaA15G2R1) at day 1 of life and slaughtered on day 7 after infection. Total RNA was extracted from the jejunal mucosa for short read. Differentially expressed genes (DEGs) between infected and CTRL groups were assessed using DESeq2 at a false discovery rate < 0.05. Infection did not affect plasma immunohematological parameters, including neutrophil, lymphocyte, monocyte, leucocyte, thrombocyte, and erythrocyte counts as well as hematocrit and hemoglobin concentration on day 7 post infection. The immune-related DEGs were selected according to the UniProt immune system process database and were used for gene ontology (GO) and pathway enrichment analysis using Cytoscape (v3.9.1). Based on GO analysis, DEGs annotated to mucosal immunity, recognizing and presenting antigens, chemotaxis of neutrophils, eosinophils, natural killer cells, B and T cells mediated by signaling pathways including toll like receptors, interleukins, tumor necrosis factor, T cell receptor, and NF-KB were upregulated, while markers of macrophages chemotaxis and cytosolic pattern recognition were downregulated. This study provides a holistic snapshot of immune-related pathways induced by C. parvum in calves, including novel and detailed feedback and feedforward regulatory mechanisms establishing the crosstalk between innate and adaptive immune response in neonate calves, which could be utilized further to develop new therapeutic strategies.
Simulation of benthic microalgae impacts on water quality in shallow water systems, Corsica River, Chesapeake Bay
Authors: Tian Richard , Cai Xun , Cerco Carl F. , Zhang Joseph Y. , Linker Lewis C.
Published: January 2024

Eutrophication and hypoxia represent an ever-growing stressor to estuaries and coastal ecosystems due to population growth and climate change. Understanding water quality dynamics in shallow water systems is particularly challenging due to the complex physical and biogeochemical dynamics and interactions among them. Within shallow waters, benthic microalgae can significantly contribute to autotrophic primary production, generate organic matter, increase dissolved oxygen consumption, and alter nutrient fluxes at the sediment–water interface, yet they have received little attention in modeling applications. A state-of-the-art modeling system, the Semi-Implicit Cross-Scale Hydroscience Integrated System Model (SCHISM), coupled with the Integrated Compartment Model (ICM) of water quality and benthic microalgae, has been implemented in the Corsica River estuary, a tributary to Chesapeake Bay, to study benthic microalgal impact on water quality in shallow water systems. The model simulation has revealed a broad impact of benthic microalgae, ranging from sediment–water interface fluxes to water column dynamics, and the effects are observed from near-field to far-field monitoring stations. High-frequency variability and non-linearity dominate benthic microalgal dynamics, sediment oxygen demand, and nutrient fluxes at the sediment–water interface. Resource competition and supply determine the spatial scope of benthic microalgal impacts on far-field stations and the whole estuary system. Our study shows that benthic microalgae are a significant factor in shallow water dynamics that needs adequate attention in future observation and modeling applications.
Vertical distribution of intraseasonal variation signals in the Kuroshio Current source area during 2018–2020
Authors: Gong Haobo , Wang Fujun , Liu Feng , Zhang Linlin , Hu Dunxin
Published: January 2024

In the Kuroshio Current (KC) source area, intraseasonal variation (ISV) plays a significant role in dynamic oceanic processes. This study used data collected from three moorings (122.7°E, 123°E, 123.3°E) along 18°N from January 2018 to May 2020 to investigate the ISVs of meridional velocities. Notably, our findings reveal that the ISV above 200 m has a period of approximately 56 days and its intensity exhibits a gradual increase toward the west. For the 500–800 m depth interval, the ISV period is 73 days at 122.7°E/18°N and 60 days at 123.3°E/18°N. This discrepancy indicates that the ISVs have different vertical structures and frequencies at 122.7°E and 123.3°E along 18°N. In particular, at 122.7°E/18°N, the distinctiveness of two different periods of ISVs in surface and subsurface layers was more pronounced in 2018 than in 2019. The analyses of eddy kinetic energy distribution and eddy tracking indicate a connection between ISV in stratification and locally generated mesoscale eddies in the KC source area. Specifically, the stronger eddy activity in 2018, in contrast with that in 2019, correlates with a more pronounced ISV. Energy analysis demonstrates a distinct positivity in the baroclinic conversion rate (BC) in the surface layer (upper 200 m) of the KC source region, surpassing the absolute value of the barotropic conversion rate (BT). This finding indicates a notable shift of energy from eddy available potential energy to eddy kinetic energy, strengthening the high-frequency ISV signals in this area. In the subsurface layer, a strong negative BT is observed west of 122.8°E, with its absolute value exceeding the BC. This finding indicates that the energy is converted from eddy kinetic energy into mean kinetic energy, resulting in the appearance of the Luzon Undercurrent (LUC) at mooring station 122.7°E/18°N, characterized by a low frequency of ISV. Contrastingly, a positive BT plays a dominant role at 123.3°E/18°N, leading to the disappearance of the LUC amid an apparent presence of high-frequency ISV.
Phaeodactylum tricornutum as a stable platform for pilot scale production and investigation of the viability of spirulina fucoxanthin as a commercial lipolysis active novel compound
Authors: Delgado-Ramallo Jesús Fidel , Álvarez-Gil Maria , Casado-Bañares Víctor , Suárez-Montes David , Sanjurjo-Muñíz Claudia
Published: January 2024

The nutraceutical market has experienced a significant growth over the last years, due to changing consumer preferences towards products of natural and organic origin. One of the main areas of interest in this field is microalgae-derived carotenoids, whose antioxidant activity protects against oxidative damage in human cells. The diatom Phaeodactylum tricornutum has been widely studied due to its high fucoxanthin content (antioxidant carotenoid). However, pilot and industrial scale experiments to realize continuous and stable production of P. tricornutum and extracted fucoxanthin are limited. For this reason, this research focuses on the study of the fucoxanthin production, going through culture, harvesting, scaling procedure and encapsulation stage. Finally, the optimal culture conditions for a fucoxanthin production of 2.5 mg/day/L were verified. Furthermore, the antioxidant capacity showed a decrease during storage, but still presented a capacity of 18 months, with improved performance when encapsulated with spirulina. The study carried out on encapsulated fucoxanthin-spirulina shows an inhibitory effect on lipogenesis at all concentrations tested in the 3T3-L1 cell line and a lipolytic efficacy at concentrations of 0.2 mg/mL and 0.1 mg/mL in the 3T3-L1 cell line.
Local application of silver nitrate as an adjuvant treatment before deep lamellar keratoplasty for fungal keratitis poorly responsive to medical treatment
Authors: Ding Gang , Gao Xin , Tan Yue , Hao Zhongkai , Wang Ximing , Zhang Chenming , Deng Aijun
Published: January 2024

Objective

The purpose of this study is to evaluate the efficacy and safety of the local application of silver nitrate (LASN) as an adjuvant treatment before deep lamellar keratoplasty (DLKP) for fungal keratitis responding poorly to medical treatment.

Methods

A total of 12 patients (12 eyes) with fungal keratitis responding poorly to medical treatment (for at least 2 weeks) were included. LASN was performed using 2% silver nitrate, the ulcer was cleaned and debrided, and then, the silver nitrate cotton stick was applied to the surface of the ulcer for a few seconds. The effect of LASN was recorded. The number of hyphae before and after treatment was determined by confocal microscope. After the condition of the ulcer improved, DLKP was performed. Fungal recurrence, best-corrected visual acuity (BCVA), loose sutures, and endothelial cell density (ECD) were recorded in detail.

Results

Clinical resolution of corneal infiltration and edema was observed, and the ulcer boundary became clear in all 12 patients after 7–9 days of LASN. Confocal microscopy showed that the number of hyphae was significantly reduced. Ocular pain peaked on days 1 and 2 after treatment, and 9 patients (75%, day 1) and 1 patient (8.3%, day 2) required oral pain medication. During the follow-up period after DLKP, no fungal recurrence and loose sutures were observed. After the operation, the BCVA of all patients improved. The mean corneal ECD was 2,166.83 ± 119.75 cells/mm2.

Conclusion

The LASN was safe and effective and can be well tolerated by patients. Eye pain can be relieved quickly. LASN as an adjuvant treatment before DLKP might be a promising therapeutic strategy.
Prenatal ultrasound diagnosis and prognosis of fetus with isolated filar cyst: a retrospective analysis
Authors: Chen Song , Tu Peng , Mu Lan
Published: January 2024

Objective

This study aimed to investigate the prenatal ultrasonographic diagnosis and prognosis of fetuses with isolated filar cysts (FCs).

Methods

The ultrasonographic features, reasons for missed diagnosis, and prognosis of eight isolated FCs diagnosed using ultrasound were analyzed retrospectively through follow-up.

Results

Eight isolated FCs showed round or fusiform cystic anechoic areas at the end of the conus medullaris. Among them, six cases were prenatally diagnosed and the other two cases were diagnosed after birth. Of the six cases diagnosed prenatally, four (66.7%) disappeared during pregnancy, and the shortest time to disappearance was 1 month after the first diagnosis. All patients were followed up without any clinical symptoms or functional abnormalities.

Conclusion

Isolated FCs may exhibit physiological variations that disappear spontaneously during pregnancy and usually have no clinical symptoms. They are usually benign and have a good prognosis. Ultrasonography is helpful for the diagnosis and follow-up of FCs.
Exploring the interplay between running exercises, microbial diversity, and tryptophan metabolism along the microbiota-gut-brain axis
Authors: Vazquez-Medina Alejandra , Rodriguez-Trujillo Nicole , Ayuso-Rodriguez Kiara , Marini-Martinez Fabiana , Angeli-Morales Roberto , Caussade-Silvestrini Gerardo , Godoy-Vitorino Filipa , Chorna Nataliya
Published: January 2024

The emergent recognition of the gut-brain axis connection has shed light on the role of the microbiota in modulating the gut-brain axis’s functions. Several microbial metabolites, such as serotonin, kynurenine, tryptamine, indole, and their derivatives originating from tryptophan metabolism have been implicated in influencing this axis. In our study, we aimed to investigate the impact of running exercises on microbial tryptophan metabolism using a mouse model. We conducted a multi-omics analysis to obtain a comprehensive insight into the changes in tryptophan metabolism along the microbiota-gut-brain axis induced by running exercises. The analyses integrated multiple components, such as tryptophan changes and metabolite levels in the gut, blood, hippocampus, and brainstem. Fecal microbiota analysis aimed to examine the composition and diversity of the gut microbiota, and taxon-function analysis explored the associations between specific microbial taxa and functional activities in tryptophan metabolism. Our findings revealed significant alterations in tryptophan metabolism across multiple sites, including the gut, blood, hippocampus, and brainstem. The outcomes indicate a shift in microbiota diversity and tryptophan metabolizing capabilities within the running group, linked to increased tryptophan transportation to the hippocampus and brainstem through circulation. Moreover, the symbiotic association between Romboutsia and A. muciniphila indicated their potential contribution to modifying the gut microenvironment and influencing tryptophan transport to the hippocampus and brainstem. These findings have potential applications for developing microbiota-based approaches in the context of exercise for neurological diseases, especially on mental health and overall well-being.
Acinetobacter baumannii: an evolving and cunning opponent
Authors: Shi Jingchao , Cheng Jianghao , Liu Shourong , Zhu Yufeng , Zhu Mingli
Published: January 2024

Acinetobacter baumannii is one of the most common multidrug-resistant pathogens causing nosocomial infections. The prevalence of multidrug-resistant A. baumannii infections is increasing because of several factors, including unregulated antibiotic use. A. baumannii drug resistance rate is high; in particular, its resistance rates for tigecycline and polymyxin—the drugs of last resort for extensively drug-resistant A. baumannii—has been increasing annually. Patients with a severe infection of extensively antibiotic-resistant A. baumannii demonstrate a high mortality rate along with a poor prognosis, which makes treating them challenging. Through carbapenem enzyme production and other relevant mechanisms, A. baumannii has rapidly acquired a strong resistance to carbapenem antibiotics—once considered a class of strong antibacterials for A. baumannii infection treatment. Therefore, understanding the resistance mechanism of A. baumannii is particularly crucial. This review summarizes mechanisms underlying common antimicrobial resistance in A. baumannii, particularly those underlying tigecycline and polymyxin resistance. This review will serve as a reference for reasonable antibiotic use at clinics, as well as new antibiotic development.
Transcriptomic analysis of cell envelope inhibition by prodigiosin in methicillin-resistant Staphylococcus aureus
Authors: Liu Xiaoxia , Wang Zonglin , You Zhongyu , Wang Wei , Wang Yujie , Wu Wenjing , Peng Yongjia , Zhang Suping , Yun Yinan , Zhang Jin
Published: January 2024

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading threat to public health as it is resistant to most currently available antibiotics. Prodigiosin is a secondary metabolite of microorganisms with broad-spectrum antibacterial activity. This study identified a significant antibacterial effect of prodigiosin against MRSA with a minimum inhibitory concentration as low as 2.5 mg/L. The results of scanning electron microscopy, crystal violet staining, and confocal laser scanning microscopy indicated that prodigiosin inhibited biofilm formation in S. aureus USA300, while also destroying the structure of the cell wall and cell membrane, which was confirmed by transmission electron microscopy. At a prodigiosin concentration of 1.25 mg/L, biofilm formation was inhibited by 76.24%, while 2.5 mg/L prodigiosin significantly reduced the vitality of MRSA cells in the biofilm. Furthermore, the transcriptomic results obtained at 1/8 MIC of prodigiosin indicated that 235and 387 genes of S. aureus USA300 were significantly up- and downregulated, respectively. The downregulated genes were related to two-component systems, including the transcriptional regulator LytS, quorum sensing histidine kinases SrrB, NreA and NreB, peptidoglycan biosynthesis enzymes (MurQ and GlmU), iron-sulfur cluster repair protein ScdA, microbial surface components recognizing adaptive matrix molecules, as well as the key arginine synthesis enzymes ArcC and ArgF. The upregulated genes were mainly related to cell wall biosynthesis, as well as two-component systems including vancomycin resistance-associated regulator, lipoteichoic acid biosynthesis related proteins DltD and DltB, as well as the 9 capsular polysaccharide biosynthesis proteins. This study elucidated the molecular mechanisms through which prodigiosin affects the cell envelope of MRSA from the perspectives of cell wall synthesis, cell membrane and biofilm formation, providing new potential targets for the development of antimicrobials for the treatment of MRSA.
Efficacy of SGLT2 inhibitors in IgA nephropathy associated with alcoholic liver cirrhosis accompanied by nephrotic syndrome: a case report
Authors: Yoshimura Yusuke , Ikuma Daisuke , Mizuno Hiroki , Kono Kei , Kinowaki Keiichi , Sugimoto Hisashi , Kamido Hisashi , Sawada Yuichiro , Mizuta Masato , Kurihara Shigekazu , Oba Yuki , Yamanouchi Masayuki , Suwabe Tatsuya , Ohashi Kenichi , Ubara Yoshifumi , Sawa Naoki
Published: January 2024

We present a 51-year-old male patient with a history of Child-Pugh Grade B alcoholic liver cirrhosis (ALC) who developed renal impairment (serum creatinine of 2.00 mg/dL) and nephrotic syndrome (a urinary protein level of 4.35 g/gCr). The patient was diagnosed with immunoglobulin A nephropathy (IgAN) associated with ALC based on findings from comprehensive evaluations, including markedly elevated serum IgA levels (883.7 mg/dL), a kidney biopsy revealing significant IgA deposition in the para-mesangial area, and a liver diagnosis showing long-standing advanced ALC. Our treatment approach involved initiating dapagliflozin therapy, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, alongside strict alcohol abstinence. Remarkably, the patient demonstrated a dramatic reduction in proteinuria within one week of dapagliflozin administration. No hypoglycemic events were observed. This case adds valuable clinical insights into the potential therapeutic role of SGLT2 inhibitors in IgAN associated with ALC. Specifically, in cases where conventional steroid therapies may be contraindicated due to coexisting comorbidities such as diabetes or obesity, dapagliflozin emerges as a potentially efficacious alternative. Further investigations are warranted to validate these preliminary observations.
Functional profile of perilesional gray matter in focal cortical dysplasia: an fMRI study
Authors: Jin Bo , Xu Jiahui , Wang Chao , Wang Shan , Li Hong , Chen Cong , Ye Linqi , He Chenmin , Cheng Hui , Zhang Lisan , Wang Shuang , Wang Jin , Aung Thandar
Published: January 2024

Objectives

We aim to investigate the functional profiles of perilesional gray matter (GM) in epileptic patients with focal cortical dysplasia (FCD) and to correlate these profiles with FCD II subtypes, surgical outcomes, and different antiseizure medications (ASMs) treatment response patterns.

Methods

Nine patients with drug-responsive epilepsy and 30 patients with drug-resistant epilepsy (11 were histologically confirmed FCD type IIa, 19 were FCD type IIb) were included. Individual-specific perilesional GM and contralateral homotopic GM layer masks were generated. These masks underwent a two-voxel (2 mm) dilation from the FCD lesion and contralateral homotopic region, resulting in 10 GM layers (20 mm). Layer 1, the innermost, progressed to Layer 10, the outermost. Amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) analyses were conducted to assess the functional characteristics of ipsilateral perilesional GM and contralateral homotopic GM.

Results

Compared to the contralateral homotopic GM, a significant reduction of ALFF was detected at ipsilateral perilesional GM layer 1 to 6 in FCD type IIa (after Bonferroni correction p < 0.005, paired t-test), whereas a significant decrease was observed at ipsilateral perilesional GM layer 1 to 2 in FCD type IIb (after Bonferroni correction p < 0.005, paired t-test). Additionally, a significant decrease of the ReHo was detected at ipsilateral perilesional GM layer 1 compared to the CHRs in FCD type IIb. Notably, complete resection of functional perilesional GM alterations did not correlate with surgical outcomes. Compared to the contralateral homotopic GM, a decreased ALFF in the ipsilateral perilesional GM layer was detected in drug-responsive patients, whereas decreased ALFF in the ipsilateral perilesional GM layer 1–6 and decreased ReHo at ipsilateral perilesional GM layer 1 were observed in drug-resistant patients (after Bonferroni correction p < 0.005, paired t-test).

Conclusion

Our findings indicate distinct functional profiles of perilesional GM based on FCD histological subtypes and ASMs’ response patterns. Importantly, our study illustrates that the identified functional alterations in perilesional GM may not provide sufficient evidence to determine the epileptogenic boundary required for surgical resection.
Pediatric low-grade glioma models: advances and ongoing challenges
Authors: Yvone Griselda Metta , Breunig Joshua J.
Published: January 2024

Pediatric low-grade gliomas represent the most common childhood brain tumor class. While often curable, some tumors fail to respond and even successful treatments can have life-long side effects. Many clinical trials are underway for pediatric low-grade gliomas. However, these trials are expensive and challenging to organize due to the heterogeneity of patients and subtypes. Advances in sequencing technologies are helping to mitigate this by revealing the molecular landscapes of mutations in pediatric low-grade glioma. Functionalizing these mutations in the form of preclinical models is the next step in both understanding the disease mechanisms as well as for testing therapeutics. However, such models are often more difficult to generate due to their less proliferative nature, and the heterogeneity of tumor microenvironments, cell(s)-of-origin, and genetic alterations. In this review, we discuss the molecular and genetic alterations and the various preclinical models generated for the different types of pediatric low-grade gliomas. We examined the different preclinical models for pediatric low-grade gliomas, summarizing the scientific advances made to the field and therapeutic implications. We also discuss the advantages and limitations of the various models. This review highlights the importance of preclinical models for pediatric low-grade gliomas while noting the challenges and future directions of these models to improve therapeutic outcomes of pediatric low-grade gliomas.
The safety and efficacy of TACE combined with HAIC, PD-1 inhibitors, and tyrosine kinase inhibitors for unresectable hepatocellular carcinoma: a retrospective study
Authors: Huang Zhongjing , Wu Ziyi , Zhang Lidong , Yan Likun , Jiang Hai , Ai Junhua
Published: January 2024

Objective

To assess the effectiveness and safety of transarterial chemoembolization (TACE) in combination with hepatic artery infusion chemotherapy (HAIC)、PD-1 inhibitors, and tyrosine kinase inhibitors(TKI) for unresectable hepatocellular carcinoma (HCC).

Methods

A retrospective analysis was performed on 158 unresectable HCC patients admitted to the First Affiliated Hospital of Nanchang University between May 2019 and October 2022. The patients were split into two groups based on the type of treatment they received: TACE combined with HAIC,PD-1 and TKI group (THPK) and TACE combined with PD-1 and TKI group (TPK). The response was evaluated using modified solid tumor Efficacy Assessment Criteria (mRECIST). Kaplan-Meier curves were used to analyze the overall survival (OS). OS-influencing factors were identified using the Cox proportional risk regression model.

Results

Finally, 63 patients who received THPK treatment and 60 patients who had TPK treatment were included. The THPK group had higher DCR (77.78% vs. 55.00%, P=0.007) and ORR (20.63% vs. 13.34%, P=0.282) than the TPK group did. The survival analysis curve also showed that the median OS was substantially longer in the THPK group than in the TPK group (OS: 21 months vs. 14 months, P=0.039). After multivariate Cox regression-corrected analysis, extrahepatic metastases (P=0.002) and methemoglobin >400 (P=0.041) were adverse influences on OS, but the THPK group (relative to the TPK group) was an independent favorable prognostic factor for OS (P=0.027). The results of the subgroup analysis showed that the addition of HAIC therapy to TPK treatment in patients with BCLC stage C, age ≦60 years, ECOG grade 0 and lobular distribution of tumors prolonged overall survival time and improved prognosis. Except for nausea, there was no difference in the adverse events between the two groups.

Conclusion

In patients with unresectable HCC, the THPK group had a longer OS and similar adverse events compared to the TPK group. In the future, TACE-HAIC in combination with targeted and immunotherapy may be a more effective therapeutic option for hepatocellular carcinoma that cannot be surgically removed.
Case Report: Refractory macrophage activation syndrome requiring high-dose anakinra, emapalumab, and etoposide therapy in early-onset systemic juvenile idiopathic arthritis associated with adenoviremia
Authors: Slaney Elizabeth D. , Modica Renee , Woolnough Leandra , Kafisheh Dina , Bell-Brunson Denise Heather , Elder Melissa
Published: January 2024

Macrophage activation syndrome (MAS) is a life-threatening condition characterized by the excessive stimulation of macrophages and T lymphocytes, provoked by infections, malignancy, and autoimmune or autoinflammatory conditions such as systemic juvenile idiopathic arthritis (sJIA). Clinical signs of sJIA may include high-spiking, quotidian fevers, lymphadenopathy, hepatosplenomegaly, and a salmon-colored migratory, evanescent rash. By contrast, MAS is characterized by unremitting fevers and diffuse, fixed, maculopapular rashes. In addition to hepatosplenomegaly and lymphadenopathy, patients with MAS may also have clinical signs of coagulopathy, as well as cardiac, lung, renal, and central nervous system dysfunction. The empiric treatment for MAS is initially high-dose IV corticosteroids, but usually requires addition of immunomodulators such as tacrolimus or a biologic such as Anakinra to control. The addition of immunotherapies for MAS has improved patient outcomes. We present a 2-year-old male patient with a history of early-onset sJIA, who presented with MAS refractory to corticosteroids and anakinra triggered by adenoviremia that required addition of emapalumab to control. We believe this is the first reported case of a combination of immunosuppressive therapy of emapalumab, etoposide, anakinra, tacrolimus, and corticosteroids used in the successful treatment of infection-induced MAS in early-onset sJIA. Given the lack of treatment guidelines and approved therapies for MAS, alternative strategies should be considered for patients with an intractable course.
Associations of COVID-19 lockdown with birth weight in China
Authors: Chen Yumeng , Fan Jingjie , Li Xiaowei , Ye Yufeng , Lv Yanyun , Zheng Suijin , Hu Jianxiong , Pu Yudong , Liu Tao
Published: January 2024

Background

During the special period of the global spread of COVID-19, pregnant women are sensitive groups to the impacts of COVID-19 epidemic. However, the effects of lockdown measures implemented in response to the COVID-19 on fetal birthweight remain unclear.

Objectives

This study investigated the associations of COVID-19 lockdown with birth weight in Chinese population.

Methods

We collected 730,153 data of participants from hospitals of five cities in the south of China, we defined the time period of level I response (1/23-2/24/2020) as level I lockdown, and women who were pregnant during level I lockdown as the exposure group. Women who were pregnant during the same calendar month from 2015 to 2019 were defined as the unexposed group. We quantitatively estimate the individual cumulative exposure dose by giving different weights to days with different emergency response levels. Generalized linear regression models were used to estimate the association between COVID-19 lockdown exposure with birth weight and risk of low birth weight (<2,500 g) and macrosomia (>4,000 g).

Results

The birth weight of the exposed group is heavier than the unexposed group (3,238.52 vs. 3,224.11 g: adjusted β = 24.39 g [95% CI: 21.88, 26.91 g]). The exposed group had a higher risk of macrosomia (2.8% vs. 2.6%; adjusted OR = 1.17 [95% CI: 1.12, 1.22]). More obvious associations were found between COVID-19 lockdown and macrosomia in women who experienced the lockdown in their early pregnancy. Women who experienced the lockdown at their 4–7 weeks of pregnancy showed statistically significant heavier birth weight than unexposed group (after adjustment): β = 1.28 (95% CI: 1.11, 1.46) g. We also observed a positive association between cumulative exposure dose of COVID-19 lockdown in all pregnant women and birth weight, after divided into four groups, Q1: β = 32.95 (95% CI: 28.16, 37.75) g; Q2: β = 18.88 (95% CI: 14.12, 23.64) g; Q3: β = 19.50 (95% CI: 14.73, 24.28) g; Q4: β = 21.82 (95% CI: 17.08, 26.56) g. However, there was no statistically significant difference in the risk of low birth weight between exposed and unexposed groups.

Conclusions

The COVID-19 lockdown measures were associated with a heavier birth weight and a higher risk of macrosomia. Early pregnancy periods may be a more susceptible exposure window for a heavier birth weight and a higher risk of macrosomia. We also observed a positive association between cumulative exposure dose of COVID-19 lockdown and birth weight. The government and health institutions should pay attention to the long-term health of the infants born during the COVID-19 lockdown period, and follow up these mothers and infants is necessary.
The clinical impact of macrophage polarity after Kasai portoenterostomy in biliary atresia
Authors: Nagayabu Kazuya , Fumino Shigehisa , Shimamura Ai , Sengoku Yuki , Higashi Mayumi , Iguchi Masafumi , Aoi Shigeyoshi , Saya Shibata , Hirai Maki , Ogi Hiroshi , Miyagawa-Hayashino Aya , Konishi Eiichi , Itoh Kyoko , Tajiri Tatsuro , Ono Shigeru
Published: January 2024

Introduction

Biliary atresia (BA) is a cholestatic hepatopathy caused by fibrosing destruction of intrahepatic and extrahepatic bile ducts, and its etiology has not been clearly revealed. In BA, liver fibrosis progression is often observed even after Kasai portoenterostomy (KPE), and more than half of cases require liver transplantation in their lifetime in Japan. Macrophages play an important role in liver fibrosis progression and are classically divided into proinflammatory (M1) and fibrotic macrophages (M2), whose phenotypic transformation is called “macrophage polarity.” The polarity has been reported to reflect the tissue microenvironment. In this study, we examined the relationship between macrophage polarity and the post-KPE clinical course.

Materials and methods

Thirty BA patients who underwent KPE in our institution from 2000 to 2020 were recruited. Multiple immunostainings for CD68, CD163, CK19, and α-SMA were carried out on liver biopsy specimens obtained at KPE. ROC curves were calculated based on each clinical event, and the correlation with the clinical data was analyzed.

Results and discussion

The M2 ratio, defined as the proportion of M2 macrophages (CD163-positive cells), was correlated inversely with the occurrence of postoperative cholangitis (AUC: 0.7602). The patients were classified into M2 high (n = 19) and non-high (n = 11) groups based on an M2 ratio value obtained from the Youden index ( = 0.918). As a result, pathological evaluations (Metavir score, αSMA area fraction, and CK19 area fraction) were not significantly different between these groups. In mild liver fibrosis cases (Metavir score = 0–2), the M2 non-high group had a significantly lower native liver survival rate than the high group (p = 0.02). Moreover, 4 out of 8 cases in the M2 non-high group underwent early liver transplantation within 2 years after KPE.

Conclusions

Non-M2 macrophages, including M1 macrophages, may be correlated with postoperative cholangitis, and the M2 non-high group in mild liver fibrosis cases had a significantly lower native liver survival rate than the high group, requiring early liver transplantation in this study. Preventing advanced liver fibrosis is a key factor in improving native liver survival for BA patients, and liver macrophages may play important roles in liver homeostasis and the promotion of inflammation and fibrosis.
Case Report: Two cases of multiples and atypical dermal sinus tracts
Authors: Spazzapan Peter , Thompson Dominic N. P.
Published: January 2024

Dermal sinus tracts (DSTs) are congenital lesions that connect the cutaneous ectoderm with the underlying neuroectodermal tissues. They are typically midline, solitary lesions. Multiple, and atypically located DSTs have been only rarely described. We present two cases of multiple and laterally located DSTs. The first presented with bacterial meningitis and two tracts in the right buttock, one of which entered the spinal canal through the S3 neural foramen. The second child had three midline lumbar DSTs, one subcutaneous dermoid cyst and one intradural epidermoid cyst. Complete surgical excision was achieved in both cases with good late follow up. Multiple or atypically located DSTs appear to carry the same risks of infection as the more common, midline, single tracts. Complete surgical excision is recommended to avoid the risks of neurological deterioration, in particular due to infection. Incomplete disjunction is the proposed developmental anomaly for DSTs, however the location of the cases presented here requires an alternative explanation.
More indications for redox-sensitive cysteine residues of the Arabidopsis 5-aminolevulinate dehydratase
Authors: Wittmann Daniel , Wang Chao , Grimm Bernhard
Published: January 2024

Redox-dependent thiol-disulfide switches of cysteine residues are one of the significant posttranslational modifications of proteins to control rapidly their stability, activity, and protein interaction. Redox control also modulates the tetrapyrrole biosynthesis (TBS). Among the redox-dependent TBS enzymes, 5-aminolevulinic acid dehydratase (ALAD) was previously recognized to interact with reductants, such a thioredoxins or NADPH-dependent thioredoxin reductase C. In this report, we aim to verify the redox sensitivity of ALAD and identify the redox-reactive cysteine residues among the six cysteines of the mature protein form Arabidopsis. Based on structural modelling and comparative studies of wild-type ALAD and ALAD mutants with single and double Cys➔Ser substitutions under oxidizing and reducing conditions, we aim to predict the dimerization and oligomerisation of ALAD as well as the crucial Cys residues for disulfide bridge formation and enzyme activity. The Cys404Ser mutation led to a drastic inactivation of ALAD and redox-dependent properties of ALAD were severely impaired, when Cys71 was simultaneously mutated with Cys152 or Cys251. Cys71 is located in a flexible N-terminal arm of ALAD, which could allow intramolecular disulfide bridges with Cys residues at the surface of the remaining globule ALAD structure. As a result, we propose different roles of Cys residues for redox control, catalytic activity and Mg2+-dependent assembly.
Multi-scenario pear tree inflorescence detection based on improved YOLOv7 object detection algorithm
Authors: Zhang Zhen , Lei Xiaohui , Huang Kai , Sun Yuanhao , Zeng Jin , Xyu Tao , Yuan Quanchun , Qi Yannan , Herbst Andreas , Lyu Xiaolan
Published: January 2024

Efficient and precise thinning during the orchard blossom period is a crucial factor in enhancing both fruit yield and quality. The accurate recognition of inflorescence is the cornerstone of intelligent blossom equipment. To advance the process of intelligent blossom thinning, this paper addresses the issue of suboptimal performance of current inflorescence recognition algorithms in detecting dense inflorescence at a long distance. It introduces an inflorescence recognition algorithm, YOLOv7-E, based on the YOLOv7 neural network model. YOLOv7 incorporates an efficient multi-scale attention mechanism (EMA) to enable cross-channel feature interaction through parallel processing strategies, thereby maximizing the retention of pixel-level features and positional information on the feature maps. Additionally, the SPPCSPC module is optimized to preserve target area features as much as possible under different receptive fields, and the Soft-NMS algorithm is employed to reduce the likelihood of missing detections in overlapping regions. The model is trained on a diverse dataset collected from real-world field settings. Upon validation, the improved YOLOv7-E object detection algorithm achieves an average precision and recall of 91.4% and 89.8%, respectively, in inflorescence detection under various time periods, distances, and weather conditions. The detection time for a single image is 80.9 ms, and the model size is 37.6 Mb. In comparison to the original YOLOv7 algorithm, it boasts a 4.9% increase in detection accuracy and a 5.3% improvement in recall rate, with a mere 1.8% increase in model parameters. The YOLOv7-E object detection algorithm presented in this study enables precise inflorescence detection and localization across an entire tree at varying distances, offering robust technical support for differentiated and precise blossom thinning operations by thinning machinery in the future.
Automatic detection of standing dead trees based on improved YOLOv7 from airborne remote sensing imagery
Authors: Zhou Hongwei , Wu Shangxin , Xu Zihan , Sun Hong
Published: January 2024

Detecting and localizing standing dead trees (SDTs) is crucial for effective forest management and conservation. Due to challenges posed by mountainous terrain and road conditions, conducting a swift and comprehensive survey of SDTs through traditional manual inventory methods is considerably difficult. In recent years, advancements in deep learning and remote sensing technology have facilitated real-time and efficient detection of dead trees. Nevertheless, challenges persist in identifying individual dead trees in airborne remote sensing images, attributed to factors such as small target size, mutual occlusion and complex backgrounds. These aspects collectively contribute to the increased difficulty of detecting dead trees at a single-tree scale. To address this issue, the paper introduces an improved You Only Look Once version 7 (YOLOv7) model that incorporates the Simple Parameter-Free Attention Module (SimAM), an unparameterized attention mechanism. This improvement aims to enhance the network’s feature extraction capabilities and increase the model’s sensitivity to small target dead trees. To validate the superiority of SimAM_YOLOv7, we compared it with four widely adopted attention mechanisms. Additionally, a method to enhance model robustness is presented, involving the replacement of the Complete Intersection over Union (CIoU) loss in the original YOLOv7 model with the Wise-IoU (WIoU) loss function. Following these, we evaluated detection accuracy using a self-developed dataset of SDTs in forests. The results indicate that the improved YOLOv7 model can effectively identify dead trees in airborne remote sensing images, achieving precision, recall and mAP@0.5 values of 94.31%, 93.13% and 98.03%, respectively. These values are 3.67%, 2.28% and 1.56% higher than those of the original YOLOv7 model. This improvement model provides a convenient solution for forest management.
Superior glucose metabolism supports NH4+ assimilation in wheat to improve ammonium tolerance
Authors: Hu Jinling , Zheng Qiaomei , Neuhäuser Benjamin , Dong Chaofeng , Tian Zhongwei , Dai Tingbo
Published: January 2024

The use of slow-release fertilizers and seed-fertilizers cause localized high-ammonium (NH4+) environments in agricultural fields, adversely affecting wheat growth and development and delaying its yield. Thus, it is important to investigate the physiological responses of wheat and its tolerance to NH4+ stress to improve the adaptation of wheat to high NH4+ environments. In this study, the physiological mechanisms of ammonium tolerance in wheat (Triticum aestivum) were investigated in depth by comparative analysis of two cultivars: NH4+-tolerant Xumai25 and NH4+-sensitive Yangmai20. Cultivation under hydroponic conditions with high NH4+ (5 mM NH4+, AN) and nitrate (5 mM NO3-, NN), as control, provided insights into the nuanced responses of both cultivars. Compared to Yangmai20, Xumai25 displayed a comparatively lesser sensitivity to NH4+ stress, as evident by a less pronounced reduction in dry plant biomass and a milder adverse impact on root morphology. Despite similarities in NH4+ efflux and the expression levels of TaAMT1.1 and TaAMT1.2 between the two cultivars, Xumai25 exhibited higher NH4+ influx, while maintaining a lower free NH4+ concentration in the roots. Furthermore, Xumai25 showed a more pronounced increase in the levels of free amino acids, including asparagine, glutamine, and aspartate, suggesting a superior NH4+ assimilation capacity under NH4+ stress compared to Yangmai20. Additionally, the enhanced transcriptional regulation of vacuolar glucose transporter and glucose metabolism under NH4+ stress in Xumai25 contributed to an enhanced carbon skeleton supply, particularly of 2-oxoglutarate and pyruvate. Taken together, our results demonstrate that the NH4+ tolerance of Xumai25 is intricately linked to enhanced glucose metabolism and optimized glucose transport, which contributes to the robust NH4+ assimilation capacity.
Coping during socio-political uncertainty
Authors: El Khoury-Malhame Myriam , Bou Malhab Sandrella , Chaaya Roni , Sfeir Michel , El Khoury Samar
Published: January 2024

Introduction

Well-being of young adults is known to be compromised in times of significant changes, such as economic and political turmoil. This study focuses on university students in Lebanon during one of the most prominent social unrests of its modern history to determine potential understudied protective factors that would predict the youth capacity to strive.

Methods

A sample of 489 university students were asked to fill an online survey including standardized questionnaires of wellbeing (WEMWBS), depression (PHQ-9), anxiety (HAM-A), intolerance of uncertainty (IUS-12), coping (Brief COPE) in addition to demographics and questions about their attitudes and future perspectives.

Results

We found increased rates of mental distress, predominantly in women, with around 80% of the sample being highly intolerant to the uncertainty climate. Results unsurprisingly show that well-being negatively correlated with anxiety, depression and intolerance of uncertainty. Overall, mental distress was found to mediate the relation between uncertainty and wellbeing, and the relation between maladaptive coping and wellbeing. Students who were intolerant of uncertainty and who used maladaptive coping strategies were more likely develop anxiety and depression and subsequently report poorer wellbeing. Conversely, having adaptive strategies was directly linked to higher well-being.

Discussion

In spite of increased distress, some university students managed to preserve their well-being within a climate of severe socio-political uprise. These findings suggest that modifying subjective experience of events and using soft skillset could alleviate young adults’ emotional distress in unstable societies.