bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutation of neurotrophic tyrosine receptor kinase can promote pan-cancer immunity and the efficacy of immunotherapy
Authors: Wang Congren , Li Yingying , Huang Jinyuan , Yan Huimeng , Zhao Bin
Published: April 2024

The Neurotrophic tyrosine receptor kinase (NTRK) family plays important roles in tumor progression and is involved in tumor immunogenicity. Here, we conducted a comprehensive bioinformatic and clinical analysis to investigate the characteristics of NTRK mutations and their association with the outcomes in pan-cancer immunotherapy. In 3888 patients across 12 cancer types, patients with NTRK-mutant tumors showed more benefit from immunotherapy in terms of objective response rate (ORR; 41.7% vs. 27.5%; P < 0.001), progress-free survival (PFS; HR = 0.80; 95% CI, 0.68–0.96; P = 0.01), and overall survival (OS; HR = 0.71; 95% CI, 0.61–0.82; P < 0.001). We further constructed and validated a nomogram to estimate survival probabilities after the initiation of immunotherapy. Multi-omics analysis on intrinsic and extrinsic immune landscapes indicated that NTRK mutation was associated with enhanced tumor immunogenicity, enriched infiltration of immune cells, and improved immune responses. In summary, NTRK mutation may promote cancer immunity and indicate favorable outcomes in immunotherapy. Our results have implications for treatment decision-making and developing immunotherapy for personalized care.
Is cholesterol both the lock and key to abnormal transmembrane signals in Autism Spectrum Disorder?
Authors: Lingwood Clifford
Published: April 2024

Disturbances in cholesterol homeostasis have been associated with ASD. Lipid rafts are central in many transmembrane signaling pathways (including mTOR) and changes in raft cholesterol content affect their order function. Cholesterol levels are controlled by several mechanisms, including endoplasmic reticulum associated degradation (ERAD) of the rate limiting HMGCoA reductase. A new approach to increase cholesterol via temporary ERAD blockade using a benign bacterial toxin-derived competitor for the ERAD translocon is suggested.

A new lock and key model for cholesterol/lipid raft dependent signaling is proposed in which the rafts provide both the afferent and efferent ‘tumblers’ across the membrane to allow ‘lock and key’ receptor transmembrane signals.
Polar lipids modify Alzheimer’s Disease pathology by reducing astrocyte pro-inflammatory signaling through platelet-activating factor receptor (PTAFR) modulation
Authors: Hans Sakshi , Stanton Janelle E. , Sauer Ann Katrin , Shiels Katie , Saha Sushanta Kumar , Lordan Ronan , Tsoupras Alexandros , Zabetakis Ioannis , Grabrucker Andreas M.
Published: April 2024

Background

Pro-inflammatory processes triggered by the accumulation of extracellular amyloid beta (Aβ) peptides are a well-described pathology in Alzheimer's disease (AD). Activated astrocytes surrounding Aβ plaques contribute to inflammation by secreting proinflammatory factors. While astrocytes may phagocytize Aβ and contribute to Aβ clearance, reactive astrocytes may also increase Aβ production. Therefore, identifying factors that can attenuate astrocyte activation and neuroinflammation and how these factors influence pro-inflammatory pathways is important for developing therapeutic and preventive strategies in AD. Here, we identify the platelet-activating factor receptor (PTAFR) pathway as a key mediator of astrocyte activation. Intriguingly, several polar lipids (PLs) have exhibited anti-inflammatory protective properties outside the central nervous system through their inhibitory effect on the PTAFR pathway. Thus, we additionally investigated whether different PLs also exert inhibitory effects on the PAF pathway in astrocytes and whether their presence influences astrocytic pro-inflammatory signaling and known AD pathologies in vitro.

Methods

PLs from salmon and yogurt were extracted using novel food-grade techniques and their fatty acid profile was determined using LC/MS. The effect of PLs on parameters such as astrocyte activation and generation of oxygen species (ROS) was assessed. Additionally, effects of the secretome of astrocytes treated with these polar lipids on aged neurons was measured.

Results

We show that PLs obtained from salmon and yogurt lower astrocyte activation, the generation of reactive oxygen species (ROS), and extracellular Aβ accumulation. Cell health of neurons exposed to the secretome of astrocytes treated with salmon-derived PLs and Aβ was less affected than those treated with astrocytes exposed to Aβ only.

Conclusion

Our results highlight a novel underlying mechanism, why consuming PL-rich foods such as fish and dairy may reduce the risk of developing dementia and associated disorders.
Recent advances in enhances peripheral nerve orientation: the synergy of micro or nano patterns with therapeutic tactics
Authors: Sharifi Majid , Kamalabadi-Farahani Mohammad , Salehi Majid , Ebrahimi-Barough Somayeh , Alizadeh Morteza
Published: April 2024

Several studies suggest that topographical patterns influence nerve cell fate. Efforts have been made to improve nerve cell functionality through this approach, focusing on therapeutic strategies that enhance nerve cell function and support structures. However, inadequate nerve cell orientation can impede long-term efficiency, affecting nerve tissue repair. Therefore, enhancing neurites/axons directional growth and cell orientation is crucial for better therapeutic outcomes, reducing nerve coiling, and ensuring accurate nerve fiber connections. Conflicting results exist regarding the effects of micro- or nano-patterns on nerve cell migration, directional growth, immunogenic response, and angiogenesis, complicating their clinical use. Nevertheless, advances in lithography, electrospinning, casting, and molding techniques to intentionally control the fate and neuronal cells orientation are being explored to rapidly and sustainably improve nerve tissue efficiency. It appears that this can be accomplished by combining micro- and nano-patterns with nanomaterials, biological gradients, and electrical stimulation. Despite promising outcomes, the unclear mechanism of action, the presence of growth cones in various directions, and the restriction of outcomes to morphological and functional nerve cell markers have presented challenges in utilizing this method. This review seeks to clarify how micro- or nano-patterns affect nerve cell morphology and function, highlighting the potential benefits of cell orientation, especially in combined approaches.

Graphical Abstract
An unusual case of primary splenic soft part alveolar sarcoma: case report and review of the literature with emphasis on the spectrum of TFE3-associated neoplasms
Authors: Guérin René , Menard Anne-Lise , Angot Emilie , Piton Nicolas , Vera Pierre , Schwarz Lilian , Sabourin Jean-Christophe , Laé Marick , Thiébaut Pierre-Alain
Published: April 2024

Background

Alveolar soft part sarcoma is a rare tumour of soft tissues, mostly localized in muscles or deep soft tissues of the extremities. In rare occasions, this tumour develops in deep tissues of the abdomen or pelvis.

Case presentation

In this case report, we described the case of a 46 year old man who developed a primary splenic alveolar soft part sarcoma. The tumour displayed typical morphological alveolar aspect, as well as immunohistochemical profile notably TFE3 nuclear staining. Detection of ASPSCR1 Exon 7::TFE3 Exon 6 fusion transcript in molecular biology and TFE3 rearrangement in FISH confirmed the diagnosis.

Conclusion

We described the first case of primary splenic alveolar soft part sarcoma, which questions once again the cell of origin of this rare tumour.
Outcomes of surgical treatment of patellar instability in children with Down syndrome
Authors: Zein Assem , Hassan Alaa Zenhom Mahmoud , Soliman Amr Mohamed , Mohamed Mohamed Mohamed Azmy
Published: April 2024

Background

patellar instability is a relatively frequent musculoskeletal disorder in children with Down syndrome (DS). However, such a condition has seldom been studied in the literature, even less its surgical treatment. Different techniques have been offered for this condition; the evidence for surgical options is scarce and primarily based on case reports or case series with few patients and heterogeneous techniques. Given this background, we aimed to evaluate the outcomes of a uniform kind of surgical procedure for such a condition that combined lateral soft tissue release, medial patellofemoral ligament (MPFL) reconstruction (using a partial-thickness quadriceps tendon autograft), the Roux-Goldthwait procedure, and V-Y quadricepsplasty (if needed).

Materials and methods

This retrospective study involved 11 skeletally immature patients (12 knees; 9 males and 2 females), 5.5 to 14.1 years of age, with DS who had patellofemoral instability (PFI) and were managed by this technique between October 2018 and March 2020. Preoperative radiography, CT scan, and MRI were performed to evaluate the physis status, lower limb alignment, patellar height, trochlear morphology, and any associated knee pathology. A functional knee assessment was done by using the Kujala score and the modified Lysholm score.

Results

The mean time of follow-up (± SD) was 47.7 ± 5.8 months (range: 39–56). Pre-operatively, the Kujala score (± SD) was 52.6 ± 14.3 (range: (31–74), and at final follow-up, it was 92.2 ± 4.4 (range: (88–98), showing a significant improvement (P < 0.001). The preoperative modified Lysholm score (± SD) was 54.3 ± 8.1 (range: 39–62), and at final follow-up it was 92.4 ± 5.3 (range: 82–96), showing a significant improvement (P < 0.001). All patients had a stable patella without a recurrence of instability and regained full ROM. There was no incidence of a patellar fracture or femoral physis injury.

Conclusions

Our proposed technique of combined soft tissue procedures, including lateral soft tissue release, MPFL reconstruction (using a partial-thickness quadriceps tendon autograft), the Roux-Goldthwait procedure, and V-Y quadricepsplasty, was an effective method for treating patellar instability in children with DS while avoiding physeal injury and patellar fracture. Functional scores and radiological outcomes were improved.

Level of evidence

IV; retrospective case series.
Del nido cardioplegia in adults: a retrospective observational study in comparison to modified St. Thomas cardioplegia in cardiac surgery
Authors: Garg Sanjeeve Kumar , Rawat Rajinder Singh , Saad Dina Afifi , Omar Ihab
Published: April 2024

Background

St. Thomas cardioplegia is commonly administered to adults, yet repeated dosing at brief intervals is required. Del Nido’s cardioplegic solution provides a prolonged duration of safe myocardial arrest, yet it was primarily intended for pediatric cardiac surgery. Recently, there has been an increasing interest in using Del Nido’s in adults; this might be due to its ease of administration and extended re-dosing intervals. This study contrasted Del Nido’s to modified St. Thomas cardioplegia in adults.

Methods

This study was conducted on 200 patients. Troponin-T was the primary outcome within the first 24 and 48 h post-surgery. Cardiopulmonary bypass time, cross-clamp time, intraoperative use of inotropic support, defibrillator and/or intra-aortic balloon were the secondary outcomes of the study.

Results

There was a significant reduction in post-operative Troponin-T levels in the first 24 and 48 h within Del Nido’s group compared to the modified St. Thomas group. The cross-clamp and cardiopulmonary bypass times were also found to be lower within Del Nido’s group.

Conclusion

This study has demonstrated a significant reduction in early postoperative Troponin-T levels as well as operative times favoring Del Nido’s in adults.
Giant unruptured sinus of Valsalva aneurysms causing angina pectoris
Authors: Hu Peng , Wan Zhedong , Sun Qianhui , Teng Peng , Ma Liang
Published: April 2024

Background

Sinus of Valsalva aneurysm (SVA) is a rare cardiac anomaly which can be congenital or acquired. Patients with SVA are commonly asymptomatic when the occupying effect of SVA is insignificant, while ruptured SVA usually causes severe symptoms including heart failure and myocardial ischemia.

Case presentation

We present an unusual case of a 64-year-old female manifesting with exertional dyspnea as well as angina pectoris for three months. Echocardiography and cardiac computed tomographic angiography confirmed unruptured left-coronary and non-coronary SVAs. The left anterior descending artery and left circumflex artery were stretched and compressed by the SVA which causing myocardial ischemia. The patient finally received aortic root replacement (Bentall procedure) and got symptom relieved.

Conclusions

Giant unruptured SVA originating from left coronary sinus is extremely rare. Our case highlights that giant SVA should be considered in cases with angina pectoris. Echocardiography and coronary computed tomographic angiography are useful and important for diagnosis. Surgery is highly recommended in patients with SVA.
Enhanced recovery after surgery program focusing on chest tube management improves surgical recovery after video-assisted thoracoscopic surgery
Authors: Yang Dan , Zheng Xi
Published: April 2024

Objective

Chest drainage is a standard procedure in thoracoscopic surgery for lung cancer. However, chest tube placement may deteriorate the ventilation capacity and increase difficulty of postoperative management of patients. The study investigated on the effects of enhanced recovery after surgery (ERAS) program focusing on chest tube management on surgical recovery of lung cancer patients.

Methods

The study population consisted of 60 patients undergoing video-assisted thoracoscopic surgery (VATS) after implementation of ERAS program and another group of 60 patients undergoing VATS before implementation of ERAS program.

Results

The mean time of first food intake was 12.9 h required for the ERAS group, which was significantly shorter than 18.4 h required for the control group (p < 0.0001). The mean time of out-of-bed activity was 14.2 h taken for the ERAS group, which was notably shorter than 22.8 h taken for the control group (p < 0.0001). The duration of chest tube placement was 68.6 h in the ERAS group, which was remarkably shorter than 92.8 h in the control group (p < 0.0001). The rate overall postoperative complications were notably lower in the ERAS group than in the control group (p = 0.018). The visual analogue score (VAS) scores on the second postoperative day exhibited significant differences between the ERAS group and the control group (p = 0.017). The patients in the ERAS group had a shorter hospitalization stay than those in the control group (p < 0.0001).

Conclusion

The study suggests the ERAS program focusing on chest tube management could improve surgical recovery, remove patient chest tube earlier, and relieve patient pain after VATS.
A case of pulmonary visceral subpleural hematoma treated by hematoma evacuation during care of post-cardiopulmonary resuscitation
Authors: Funaki Yutaka , Hirai Kyoji
Published: April 2024

Background

The occurrence of pulmonary visceral subpleural hematoma during care of post-cardiopulmonary resuscitation including chest compressions and anticoagulant and antiplatelet therapies is extremely rare. Also, there are few reports of treatment of visceral subpleural hematoma, most of which are treated by lung resection. Here we describe a rare case that pulmonary visceral subpleural hematoma arose during post-cardiopulmonary resuscitation care and was treated by hematoma evacuation.

Case presentation

A 58-year-old male with no smoking history and, past medical histories of rheumatoid arthritis, chronic atrial fibrillation, hypertension, diabetes, and dyslipidemia developed ventricular fibrillation due to myocardial infarction and fainted. He received bystander cardiopulmonary resuscitation and defibrillation by the ambulance crew and had return of spontaneous circulation. After transfer to our hospital, the patient underwent percutaneous catheter intervention and stenting with a diagnosis of myocardial infarction, followed by anticoagulant and antiplatelet therapies. On the 8th hospital day, chest radiography suggested right lower lobe pneumonia, and subsequent chest computed tomography revealed pulmonary hematoma in the visceral subpleural area from S6 to S10. Since no improvement was observed in hypoxemia, treatment was considered necessary. First, an attempt at computed tomography-guided drainage of hematoma was made, but insertion of the Pig-tail catheter was difficult due to hardness of the hematoma. Next, evacuation of hematoma was performed on the 13th hospital day. The hematoma was located in the visceral subpleural area and was removed by incising the pleura. TachoSil Tissue Sealing sheet and Polyglycoal acid sheet were applied to the sites of air leakage and oozing after hematoma evacuation. No re-bleeding or air leakage was observed after the treatment, and the patient was discharged on the 26th hospital day after an uneventful course.

Conclusions

Pulmonary visceral subpleural hematoma may occur during post-cardiopulmonary resuscitation care, including chest compressions and anticoagulant and antiplatelet therapies. In our case, CT-guided puncture and drainage was difficult and surgical treatment by incision of the visceral pleura and hematoma evacuation alone was done successfully.
Feasibility and applicability of self-sampling based online cervical cancer screening: findings from the China online cervical cancer screening trial
Authors: Zhang Yi , Du Hui , Wang Chun , Huang Xia , Qu Xinfeng , Wu Ruifang
Published: April 2024

Objective

This study aims to evaluate the feasibility and applicability of an online cervical cancer screening program using a website as the public platform and self-collected HPV testing as the primary screening method.

Methods

A website (mcareu.com) was developed to facilitate the online cervical cancer screening program by Peking University Shenzhen Hospital (PUSH). Women in Shenzhen could register for participation on the website by providing essential demographic data. Sampling kits and specimens were delivered through regular logistics. Eligible women collected vaginal samples by themselves using the provided kits and in referring of the graphic guidance. The specimens were tested for HPV at PUSH or a reference lab, and the results were accessible on the website through participants' personal accounts. Participants who tested positive for high-risk HPV were scheduled for colposcopy and biopsies. The demographic and social background data of the eligible participants were analyzed to evaluate the feasibility and applicability of the online screening approach.

Results

A total of 1712 applicants registered for participation, with 99.9% (1710/1712) completing registration with full data. The analysis included 1560 applicants aged 30–59, with an average age of 41.1 (± 7.6) years. Among them, 83.3% (1299/1560) provided self-collected samples for testing. Age-group analysis revealed an overall sample provision rate (SPR) exceeded 80% in all age groups. A significant difference in SPR was observed only between the 30–34 and 45–49 age groups (p < 0.05), while no significant differences were found among other age groups. 99.7% of the samples were tested qualified, and there was no significant difference in sampling failure rate among age groups. Analysis of demographic and social elements showed no significant impact on the rates of sample provision among groups in most of the social elements but the medical insurance and the monthly family-incomes.

Conclusion

The findings demonstrate that online cervical cancer screening is reliable for self-registration, self-sampling, and self-ordering for specimen transportation. It is suitable for women of all ages needing to be screened, irrespective of social elements, and effectively facilitates screening for women with limited access to medical resources. Therefore, online screening holds promise as an effective approach to increase screening coverage.
Kidney and urogenital abnormalities in Down syndrome: a meta-analysis
Authors: Rossetti Caterina Maria , Simonetti Giacomo D. , Bianchetti Mario G. , Lava Sebastiano A. G. , Treglia Giorgio , Agostoni Carlo , Milani Gregorio P. , de Winter J. Peter
Published: April 2024

Background

Reviews on Down syndrome do not or only marginally address the issue of kidney and urogenital tract abnormalities, and lower urinary tract dysfunctions. Hence, we performed a meta-analysis of the literature. 

Methods

A literature search was undertaken in the Library of Medicine, Web of Science and Excerpta Medica. The search algorithm combined various keywords: (Down syndrome OR trisomy 21 OR mongolism) AND (kidney OR urinary tract OR bladder) AND (malformation OR dysfunction OR anomaly OR abnormality OR size). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was used.

Results

Eight case-control studies were retained for the final analysis. Three studies addressed the prevalence of kidney and urogenital tract abnormalities: an increased pooled relative risk of 5.49 (95%-CI: 1.78–16.93) was observed in Down syndrome. Penile malformations, obstructive malformations (including urethral valves), dilated urinary tract system, and kidney hypodysplasia were especially common. Three reports addressed the prevalence of lower urinary tract dysfunction: an increased pooled relative risk of 2.95 (95%-CI: 1.15–7.56) was observed. Finally, an autoptic study and an ultrasound study disclosed a reduced kidney size in Down syndrome.

Conclusions

This meta-analysis indicates that abnormalities of the kidney and urogenital tract, lower urinary tract dysfunctions, and a reduced kidney size present with an increased frequency in individuals with Down syndrome.
Echinococcus granulosus ubiquitin-conjugating enzymes (E2D2 and E2N) promote the formation of liver fibrosis in TGFβ1-induced LX-2 cells
Authors: Du Xiaodi , Hua Ruiqi , He Xue , Hou Wei , Li Shengqiong , Yang Aiguo , Yang Guangyou
Published: April 2024

Background

Cystic echinococcosis (CE) is a widespread zoonosis caused by the infection with Echinococcus granulosus sensu lato (E. granulosus s.l.). CE cysts mainly develop in the liver of intermediate hosts, characterized by the fibrotic tissue that separates host organ from parasite. However, precise mechanism underlying the formation of fibrotic tissue in CE remains unclear.

Methods

To investigate the potential impact of ubiquitin-conjugating enzymes on liver fibrosis formation in CE, two members of ubiquitin-conjugating (UBC) enzyme of Echinococcus granulosus (EgE2D2 and EgE2N) were recombinantly expressed in Escherichia coli and analyzed for bioinformatics, immunogenicity, localization, and enzyme activity. In addition, the secretory pathway and their effects on the formation of liver fibrosis were also explored.

Results

Both rEgE2D2 and rEgE2N possess intact UBC domains and active sites, exhibiting classical ubiquitin binding activity and strong immunoreactivity. Additionally, EgE2D2 and EgE2N were widely distributed in protoscoleces and germinal layer, with differences observed in their distribution in 25-day strobilated worms. Further, these two enzymes were secreted to the hydatid fluid and CE-infected sheep liver tissues via a non-classical secretory pathway. Notably, TGFβ1-induced LX-2 cells exposed to rEgE2D2 and rEgE2N resulted in increasing expression of fibrosis-related genes, enhancing cell proliferation, and facilitating cell migration.

Conclusions

Our findings suggest that EgE2D2 and EgE2N could secrete into the liver and may interact with hepatic stellate cells, thereby promoting the formation of liver fibrosis.

Graphical Abstract
Analysis of long-range chromatin contacts, compartments and looping between mouse embryonic stem cells, lens epithelium and lens fibers
Authors: Camerino Michael , Chang William , Cvekl Ales
Published: April 2024

Background

Nuclear organization of interphase chromosomes involves individual chromosome territories, “open” and “closed” chromatin compartments, topologically associated domains (TADs) and chromatin loops. The DNA- and RNA-binding transcription factor CTCF together with the cohesin complex serve as major organizers of chromatin architecture. Cellular differentiation is driven by temporally and spatially coordinated gene expression that requires chromatin changes of individual loci of various complexities. Lens differentiation represents an advantageous system to probe transcriptional mechanisms underlying tissue-specific gene expression including high transcriptional outputs of individual crystallin genes until the mature lens fiber cells degrade their nuclei.

Results

Chromatin organization between mouse embryonic stem (ES) cells, newborn (P0.5) lens epithelium and fiber cells were analyzed using Hi-C. Localization of CTCF in both lens chromatins was determined by ChIP-seq and compared with ES cells. Quantitative analyses show major differences between number and size of TADs and chromatin loop size between these three cell types. In depth analyses show similarities between lens samples exemplified by overlaps between compartments A and B. Lens epithelium-specific CTCF peaks are found in mostly methylated genomic regions while lens fiber-specific and shared peaks occur mostly within unmethylated DNA regions. Major differences in TADs and loops are illustrated at the ~ 500 kb Pax6 locus, encoding the critical lens regulatory transcription factor and within a larger ~ 15 Mb WAGR locus, containing Pax6 and other loci linked to human congenital diseases. Lens and ES cell Hi-C data (TADs and loops) together with ATAC-seq, CTCF, H3K27ac, H3K27me3 and ENCODE cis-regulatory sites are shown in detail for the Pax6, Sox1 and Hif1a loci, multiple crystallin genes and other important loci required for lens morphogenesis. The majority of crystallin loci are marked by unexpectedly high CTCF-binding across their transcribed regions.

Conclusions

Our study has generated the first data on 3-dimensional (3D) nuclear organization in lens epithelium and lens fibers and directly compared these data with ES cells. These findings generate novel insights into lens-specific transcriptional gene control, open new research avenues to study transcriptional condensates in lens fiber cells, and enable studies of non-coding genetic variants linked to cataract and other lens and ocular abnormalities.
Unraveling the interplay of ferroptosis and immune dysregulation in diabetic kidney disease: a comprehensive molecular analysis
Authors: Jiao Yuanyuan , Liu Xinze , Shi Jingxuan , An Jiaqi , Yu Tianyu , Zou Guming , Li Wenge , Zhuo Li
Published: April 2024

Background

Diabetic kidney disease (DKD) is a primary microvascular complication of diabetes with limited therapeutic effects. Delving into the pathogenic mechanisms of DKD and identifying new therapeutic targets is crucial. Emerging studies reveal the implication of ferroptosis and immune dysregulation in the pathogenesis of DKD, however, the precise relationship between them remains not fully elucidated. Investigating their interplay is pivotal to unraveling the pathogenesis of diabetic kidney disease, offering insights crucial for targeted interventions and improved patient outcomes.

Methods

Integrated analysis, Consensus clustering, Machine learning including Generalized Linear Models (GLM), RandomForest (RF), Support Vector Machine (SVM) and Extreme Gradient Boosting (xGB), Artificial neural network (ANN) methods of DKD glomerular mRNA sequencing were performed to screen DKD-related ferroptosis genes.CIBERSORT, ESTIMATE and ssGSEA algorithm were used to assess the infiltration of immune cells between DKD and control groups and in two distinct ferroptosis phenotypes. The ferroptosis hub genes were verified in patients with DKD and in the db/db spontaneous type 2 diabetes mouse model via immunohistochemical and Western blotting analyses in mouse podocyte MPC5 and mesangial SV40-MES-13 cells under high-glucose (HG) conditions.

Results

We obtained 16 differentially expressed ferroptosis related genes and patients with DKD were clustered into two subgroups by consensus clustering. Five ferroptosis genes (DUSP1,ZFP36,PDK4,CD44 and RGS4) were identified to construct a diagnostic model with a good diagnosis performance in external validation. Analysis of immune infiltration revealed immune heterogeneity between DKD patients and controls.Moreover, a notable differentiation in immune landscape, comprised of Immune cells, ESTIMATE Score, Immune Score and Stromal Score was observed between two FRG clusters. GSVA analysis indicated that autophagy, apoptosis and complement activation can participate in the regulation of ferroptosis phenotypes. Experiment results showed that ZFP36 was significantly overexpressed in both tissue and cells while CD44 was on the contrary.Meanwhile,spearman analysis showed both ZFP36 and CD44 has a strong correlation with different immune cells,especially macrophage.

Conclusion

The regulation of the immune landscape in DKD is significantly influenced by the focal point on ferroptosis. Newly identified ferroptosis markers, CD44 and ZFP36, are poised to play essential roles through their interactions with macrophages, adding substantial value to this regulatory landscape.
Mutation analysis of BCR-ABL1 kinase domain in chronic myeloid leukemia patients with tyrosine kinase inhibitors resistance: a Malaysian cohort study
Authors: Seman Zahidah Abu , Ahid Fadly , Kamaluddin Nor Rizan , Sahid Ermi Neiza Mohd , Esa Ezalia , Said Siti Shahrum Muhamed , Azman Norazlina , Mat Wan Khairull Dhalila Wan , Abdullah Julia , Ali Nurul Aqilah , Khalid Mohd Khairul Nizam Mohd , Yusoff Yuslina Mat
Published: April 2024

Objective

Mutational analysis of BCR::ABL1 kinase domain (KD) is a crucial component of clinical decision algorithms for chronic myeloid leukemia (CML) patients with failure or warning responses to tyrosine kinase inhibitor (TKI) therapy. This study aimed to detect BCR::ABL1 KD mutations in CML patients with treatment resistance and assess the concordance between NGS (next generation sequencing) and Sanger sequencing (SS) in detecting these mutations.

Results

In total, 12 different BCR::ABL1 KD mutations were identified by SS in 22.6% (19/84) of patients who were resistant to TKI treatment. Interestingly, NGS analysis of the same patient group revealed an additional four different BCR::ABL1 KD mutations in 27.4% (23/84) of patients. These mutations are M244V, A344V, E355A, and E459K with variant read frequency below 15%. No mutation was detected in 18 patients with optimal response to TKI therapy. Resistance to TKIs is associated with the acquisition of additional mutations in BCR::ABL1 KD after treatment with TKIs. Additionally, the use of NGS is advised for accurately determining the mutation status of BCR::ABL1 KD, particularly in cases where the allele frequency is low, and for identifying mutations across multiple exons simultaneously. Therefore, the utilization of NGS as a diagnostic platform for this test is very promising to guide therapeutic decision-making.
Endoplasmic reticulum stress-related genes as prognostic and immunogenic biomarkers in prostate cancer
Authors: Wan Lilin , Fan Yunxia , Wu Tiange , Liu Yifan , Zhang Ruixin , Chen Saisai , Zhao Chenggui , Xue Yifeng
Published: April 2024

Background

The metastasis and aggressive nature of prostate cancer (PCa) has become a major malignancy related threat that concerns men’s health. The efficacy of immune monotherapy against PCa is questionable due to its lymphocyte-suppressive nature.

Method

Endoplasmic reticulum stress- (ERS-) and PCa-prognosis-related genes were obtained from the Molecular Signatures Database and the Cancer Genome Atlas database. The expression, prognosis and immune infiltration values of key genes were explored by “survival R package”, “rms”, “xCELL algorithm”, and univariate–multivariate Cox and LASSO regression analyses. The “consensus cluster plus R package” was used for cluster analysis.

Result

As ERS-related genes, ERLIN2 and CDK5RAP3 showed significant expressional, prognostic and clinic-pathologic values. They were defined as the key genes significantly correlated with immune infiltration and response. The nomogram was constructed with T-stage and primary treatment outcome, and the risk-prognostic model was constructed in the following way: Riskscore = (− 0.1918) * ERLIN2 + (0.5254) * CDK5RAP3. Subsequently, prognostic subgroups based on key genes classified the high-risk group as a pro-cancer subgroup that had lower mutation rates of critical genes (SPOP and MUC16), multiple low-expression immune-relevant molecules, and differences in macrophages (M1 and M2) expressions. Finally, ERLIN2 as an anti-oncogene and CDK5RAP3 as a pro-oncogene were further confirmed by cell phenotype assays and immunohistochemistry.

Conclusion

We identified ERLIN2 and CDK5RAP3 as ERS-related genes with important prognostic and immunologic values, and classified patients between high- and low-risk subgroups, which provided new prognostic markers, immunotherapeutic targets, and basis for prognostic assessments.
Influence of vaccination on critical COVID-19 patients with acute respiratory failure: a retrospective cohort study
Authors: Shen Hsiao-Chin , Huang Jhong-Ru , Sun Chuan-Yen , Liao Ying-Ting , Ko Hung-Jui , Chang Chih-Jung , Feng Jia-Yih , Chen Yuh-Min , Chen Wei-Chih , Yang Kuang-Yao
Published: April 2024

Background

Despite vaccines’ effectiveness in reducing COVID-19 infection rates and disease severity, their impact on critical patients presenting with acute respiratory failure is elusive. The aim of this study was to further investigate the influence of vaccination on mortality rates among severely ill COVID-19 patients experiencing acute respiratory failure.

Methods

This retrospective cohort study was carried out at a tertiary medical center in Taiwan. From April to September 2022, patients who tested positive for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through reverse transcription polymerase chain reaction (RT-PCR) and subsequently experienced acute respiratory failure were included in the study. Baseline characteristics, including vaccination history, along with information regarding critical illness and clinical outcomes, were gathered and compared between patients who received the vaccine and those who did not.

Results

A total of 215 patients with COVID-19 exhibiting acute respiratory failure, as confirmed via RT‒PCR, were included in the analysis. Of this cohort, sixty-six (30.7%) patients died within 28 days. Neither administration of the vaccine nor achievement of primary series vaccination status had a significantly different effect on 28 day mortality, number of viral shedding events, acute respiratory distress syndrome (ARDS) incidence or other clinical outcomes. Patients who received the booster vaccine and completed the primary series showed a tendency of increased 28 days of ventilator-free status, though this difference was not statistically significant (p = 0.815).

Conclusions

Vaccination status did not significantly influence mortality rates, the occurrence of ARDS, or the viral shedding duration in COVID-19 patients with acute respiratory failure.
Allostatic load and frailty do not covary significantly among older residents of Greater Poland
Authors: Jeszka Jan , Hummel Darian , Woźniewicz Malgorzata , Morinaka Tomoko , Sone Yoshiaki , Crews Douglas E.
Published: April 2024

Background

Physiological dysregulation/allostatic load and the geriatric syndrome frailty increase with age. As a neurophysiological response system, allostasis supports survival by limiting stressor-related damage. Frailty reflects decreased strength, endurance, and physical abilities secondary to losses of muscle and bone with age. One suggestion, based on large cohort studies of person’s ages 70 + years, is that frailty contributes to allostatic load at older ages. However, small community-based research has not confirmed this specific association.

Methods

To further explore possible associations between allostatic load and frailty, we enrolled 211 residents of Greater Poland aged 55–91 years living in a small village (Nekla, N = 104) and an urban center and capital of Greater Poland (Poznan, N = 107). For each, we recorded age, self-reported sex, and residence and estimated a 10-biomarker allostatic load score (ALS) and an 8-biomarker frailty index. We anticipated the following: higher ALS and frailty among men and rural residents; for frailty but not ALS to be higher at older ages; significant associations of ALS with sex and place of residence, but not with age or frailty. The significance of observed associations was evaluated by t-tests and multivariate regression.

Results

ALS did not vary significantly between men and women nor between Nekla and Poznan residents overall. However, women showed significantly higher frailty than men. Nekla men showed significantly higher ALS but not frailty, while Nekla women showed nonsignificantly higher ALS and lower frailty than Poznan. In multivariate analyses, neither age, nor sex, nor residence was associated with ALS. Conversely, age, sex, and residence, but not ALS, are associated significantly with frailty. In Nekla, both age and sex, but in Poznan only age, are associated with ALS. Among women, both age and residence, but among men, neither associated with ALS. In no case did ALS associate significantly with frailty.

Conclusion

In this sample, lifestyle factors associated with residence, age, and sex influence stress-related physiology, less so in women, while ALS and frailty do not covary, suggesting their underlying promoters are distinct. Similar complex associations of physiological dysregulation with frailty, age, sex, and residence likely exist within many local settings. Knowledge of this variation likely will aid in supporting health and healthcare services among seniors.
Personality of organizational social media accounts and its relationship with characteristics of their photos: analyses of startups’ Instagram photos
Authors: Kim Yunhwan
Published: April 2024

Background

Organizational accounts of social networking sites (SNSs) are similar to individual accounts in terms of their online behaviors. Thus, they can be investigated from the perspective of personality, as individual accounts have been in the literature. Focusing on startups’ Instagram accounts, this study aimed to investigate the characteristics of Big Five personality traits and the relationships between the traits and the characteristics of photos in organizational SNS accounts.

Methods

The personality traits of 108 startups’ accounts were assessed with an online artificial intelligence service, and a correspondence analysis was performed to identify the key dimensions where the account were distributed by their personality. Photo features were extracted at the content and pixel levels, and correlational analyses between personality traits and photo features were conducted. Moreover, predictive analyses were performed using random forest regression models.

Results

The results indicated that personality of the accounts had high openness, agreeableness, and conscientiousness and moderate extraversion and neuroticism. In addition, the two dimensions of high vs. low in neuroticism and extraversion/openness vs. conscientiousness/agreeableness in the accounts’ distribution by their personality traits were identified. Conscientiousness was the trait most associated with photo features—in particular, with content category, pixel-color, and visual features, while agreeableness was the trait least associated with photo features. Neuroticism was mainly correlated with pixel-level features, openness was correlated mainly with pixel-color features, and extraversion was correlated mainly with facial features. The personality traits, except neuroticism, were predicted from the photo features.

Conclusions

This study applied the theoretical lens of personality, which has been mainly used to examine individuals’ behaviors, to investigate the SNS communication of startups. Moreover, it focused on the visual communication of organizational accounts, which has not been actively studied in the literature. This study has implications for expanding the realm of personality research to organizational SNS accounts.
Phosphorus fractions affect fungal compositions and functions under land use conversions in saline-alkali soil in northeastern China
Authors: Hu Juan , Huang Yingxin , Zhou Daowei
Published: April 2024

Background

Little is known about the link between the fungal community and phosphorus fractions when land use is converted from cropland to grassland in saline-alkali soil in northeastern China. Therefore, in this study, the diversity, composition, and function of fungi, as well as phosphorus fractions including Olsen-P and inorganic phosphorus (Pi), were investigated under land use conversions from maize cropland (MC) to alfalfa (Medicago sativa L.) (AG), Leymus chinensis (LG), and natural restored grasslands (RG).

Results

The results showed that the Pi fractions of Ca8-P, Fe-P, Ca2-P, and Ca10-P were closely related with Olsen-P. Significantly increased Olsen-P content was found in 0–10 cm soil layer in the AG treatment, relative to LG and RG treatments (P < 0.05). The occluded P content in 0–10 cm and the Al-P content in 10–20 cm in the RG treatment were the highest. The RG treatment increased the Shannon index of fungi, as well as the abundances of phyla Mortierellomycota and phyla Glomeromycota. Higher abundance of genus Mortierella and lower abundance of genus Cladosporium were observed at RG treatment. Moreover, the RG treatment greatly reduced the abundance of plant pathogens and enhanced the abundances of mycorrhizal and ectomycorrhizal. The Olsen-P was positively correlated with the abundance of plant pathogen (P < 0.01), and the Olsen-P, Ca2-P, and Fe–P were negatively correlated with both the abundances of mycorrhizal and ectomycorrhizal (P < 0.05).

Conclusion

Land use conversion from maize cropland to natural restored grassland could reduce plant pathogens and enhance useful fungi by decreasing the availability of phosphorus.

Graphical Abstract
Indian voters’ attitude and behavior toward a political brand for producing green products: a mediation model
Authors: Yadav Parul , Agarwal Bhawna , Mathew Jones
Published: April 2024

This study explores the attitude–behavior relationship among voters for political party brands that use a sustainable or green marketing approach. A structural equation modeling is used to analyze data collected from 1771 respondents who are registered Indian voters in this case. A positive attitude toward a political brand is compared to intentions to vote for the same brand. According to the findings, political brands create a more environmentally friendly product in the form of green actions because doing so encourages consumers to think favorably of the political brand, which results in them voting for it. As a result, authors are able to identify a positive attitude–behavior relationship for political brands among voters.
Hemostatic Effects of Exercise-related Hypoglycemia in Male Persons With Type 1 Diabetes
Authors: Hagelqvist Per Gustav , Andersen Andreas , Maytham Kaisar , Andreasen Christine Rode , Engberg Susanne , Pedersen-Bjergaard Ulrik , Forman Julie Lyng , Johansson Pär , Lykkesfeldt Jens , Knop Filip Krag , Vilsbøll Tina
Published: April 2024

Context

People with type 1 diabetes (T1D) are at increased risk of thrombosis compared to the general population; however, the underlying mechanisms remain unclear. Hypoglycemia induced at rest can induce coagulation activation, but little is known about the hemostatic effects of exercise-related hypoglycemia in people with T1D.

Objective

We compared hemostatic profiles of individuals with T1D with healthy controls and explored hemostatic effects of hypoglycemia, induced with or without exercise, in participants with T1D.

Methods

Thrombelastography was used for a baseline hemostatic comparison between fifteen men with T1D and matched healthy controls. In addition, the participants with T1D underwent two euglycemic-hypoglycemic clamp days in a randomized, crossover fashion. Hypoglycemia was induced with the participants at rest (Hypo-rest) or during exercise (Hypo-exercise). Thrombelastography provides data on the rate of coagulation activation (R-time), the rate of clot formation (K-time, α-Angle), the maximum clot amplitude (MA), the functional fibrinogen contribution to the clot strength (MA-FF) and the fibrinolysis (LY-30).

Results

The T1D group exhibited a faster rate of coagulation activation (shorter R-time) and a faster clot formation (greater α-Angle) compared with the controls. During the clamp experiments, Hypo-exercise induced an increased clot strength (MA) with a mean difference from baseline of 2.77 mm (95% CI, 2.04-3.51) accompanied with a decreased fibrinolysis (LY-30) of −0.45 percentage point (−0.60 to −0.29). Hypo-rest resulted in increased functional fibrinogen (MA-FF) of 0.74 mm (0.13-1.36) along with an increased fibrinolysis (LY-30) of 0.54 percentage point (0.11-0.98).

Conclusion

Individuals with T1D exhibit a hypercoagulable hemostatic profile compared with healthy controls and exercise-related hypoglycemia may increase the susceptibility to thrombosis via both procoagulant and antifibrinolytic effects.
The Transformation of Prewar Blues into Postwar Rhythm and Blues
Authors: Stoia Nicholas
Published: April 2024

The transformation of blues into rhythm and blues in the mid-twentieth century mirrored the experience of migrants who traveled from the South and adapted to bustling city life in the North and Midwest. When millions of Black Americans moved to cities during the Great Migration, traditional blues traveled with them, but the faster pace of urban life engendered new approaches to blues that reflected the new environment, and rhythm and blues emerged in the early postwar period as an urbanized transformation of the earlier genre.

Rhythm and blues was loud, emphatically energetic, and, through greater use of new modern instruments, highly electrified. These attributes were, as many have observed, artistic responses to the new urban setting and marked a distinct divergence from the genre's prewar origins.

What have received less attention than timbre, tempo, and volume, though, are the many new formal approaches that mark the new style: the urban environment engendered a corresponding creative explosion of new variants on the traditional twelve-bar form, many of them characterized by faster textual pacing, greater phrase-rhythmic density, and elaborate stylization. These transformations are the formal counterparts to the electrification and livelier tempos that mark the urbanization of blues and its metamorphosis into a new postwar genre, and they appear throughout the work of many pivotal rhythm and blues musicians, including Willie Dixon, Ruth Brown, Howlin' Wolf, Ray Charles, Big Mama Thornton, Fats Domino, Chuck Berry, and Little Richard, the main artists explored in this study.