bluuebunny/crossref_metadata_2025 huggingface dataset:
BM-MSCs display altered gene expression profiles in B-cell acute lymphoblastic leukemia niches and exert pro-proliferative effects via overexpression of IFI6
Authors: Pan Chengyun , Hu Tianzhen , Liu Ping , Ma Dan , Cao Shuyun , Shang Qin , Zhang Luxin , Chen Qingzhen , Fang Qin , Wang Jishi
Published: September 2023

Background

The tumor microenvironment (TME) is a supportive environment responsible for promoting the growth and proliferation of tumor cells. Current studies have revealed that the bone marrow mesenchymal stem cells (BM-MSCs), a type of crucial stromal cells in the TME, can promote the malignant progression of tumors. However, in the adult B-cell acute lymphoblastic leukemia (B-ALL) microenvironment, it is still uncertain what changes in BM-MSCs are induced by leukemia cells.

Methods

In this study, we mimicked the leukemia microenvironment by constructing a BM-MSC–leukemia cell co-culture system. In vitro cell experiments, in vivo mouse model experiments, lentiviral transfection and transcriptome sequencing analysis were used to investigate the possible change of BM-MSCs in the leukemia niche and the potential factors in BM-MSCs that promote the progression of leukemia.

Results

In the leukemia niche, the leukemia cells reduced the MSCs' capacity to differentiate towards adipogenic and osteogenic subtypes, which also promoted the senescence and cell cycle arrest of the MSCs. Meanwhile, compared to the mono-cultured MSCs, the gene expression profiles of MSCs in the leukemia niche changed significantly. These differential genes were enriched for cell cycle, cell differentiation, DNA replication, as well as some tumor-promoting biofunctions including protein phosphorylation, cell migration and angiogenesis. Further, interferon alpha-inducible protein 6 (IFI6), as a gene activated by interferon, was highly expressed in leukemia niche MSCs. The leukemia cell multiplication was facilitated evidently by IFI6 both in vitro and in vivo. Mechanistically, IFI6 might promote leukemia cell proliferation by stimulating SDF-1/CXCR4 axis, which leads to the initiation of downstream ERK signaling pathway. As suggested by further RNA sequencing analysis, the high IFI6 level in MSCs somewhat influenced the gene expression profile and biological functions of leukemia cells.

Conclusions

BM-MSCs in the leukemia niche have varying degrees of changes in biological characteristics and gene expression profiles. Overexpression of IFI6 in BM-MSCs could be a key factor in promoting the proliferation of B-ALL cells, and this effect might be exerted through the SDF-1/CXCR4/ERK signal stimulation. Targeting IFI6 or related signaling pathways might be an important measure to reduce the leukemia cell proliferation.
Micro-inflammation related gene signatures are associated with clinical features and immune status of fibromyalgia
Authors: Yao Menghui , Wang Shuolin , Han Yingdong , Zhao He , Yin Yue , Zhang Yun , Zeng Xuejun
Published: September 2023

Background

Fibromyalgia (FM) is a multifaceted disease. Along with the genetic, environmental and neuro-hormonal factors, inflammation has been assumed to have role in the pathogenesis of FM. The aim of the present study was to explore the differences in clinical features and pathophysiology of FM patients under different inflammatory status.

Methods

The peripheral blood gene expression profile of FM patients in the Gene Expression Omnibus database was downloaded. Differentially expressed inflammatory genes were identified, and two molecular subtypes were constructed according to these genes used unsupervised clustering analysis. The clinical characteristics, immune features and pathways activities were compared further between the two subtypes. Then machine learning was used to perform the feature selection and construct a classification model.

Results

The patients with FM were divided into micro-inflammation and non-inflammation subtypes according to 54 differentially expressed inflammatory genes. The micro-inflammation group was characterized by more major depression (p = 0.049), higher BMI (p = 0.021), more active dendritic cells (p = 0.010) and neutrophils. Functional enrichment analysis showed that innate immune response and antibacterial response were significantly enriched in micro-inflammation subtype (p < 0.050). Then 5 hub genes (MMP8, ENPP3, MAP2K3, HGF, YES1) were screened thought three feature selection algorithms, an accurate classifier based on the 5 hub DEIGs and 2 clinical parameters were constructed using support vector machine model. Model scoring indicators such as AUC (0.945), accuracy (0.936), F1 score (0.941), Brier score (0.079) and Hosmer–Lemeshow goodness-of-fit test (χ2 = 4.274, p = 0.832) proved that this SVM-based classifier was highly reliable.

Conclusion

Micro-inflammation status in FM was significantly associated with the occurrence of depression and activated innate immune response. Our study calls attention to the pathogenesis of different subtypes of FM.
Cantharidin induces apoptosis of human triple negative breast cancer cells through mir-607-mediated downregulation of EGFR
Authors: Yang Tianfeng , Yu Runze , Cheng Cheng , Huo Jian , Gong Zhengyan , Cao Hanbing , Hu Yu , Dai Bingling , Zhang Yanmin
Published: September 2023

Background

Triple negative breast cancer (TNBC) is a major subtype of breast cancer, with limited therapeutic drugs in clinical. Epidermal growth factor receptor (EGFR) is reported to be overexpressed in various TNBC cells. Cantharidin is an effective ingredient in many clinical traditional Chinese medicine preparations, such as Delisheng injection, Aidi injection, Disodium cantharidinate and vitamin B6 injection. Previous studies showed that cantharidin had satisfactory pharmacological activity on a variety of tumors. In this study, we aimed to study the therapeutic potential of cantharidin for TNBC treatment by targeting EGFR, and expound its novel regulator miR-607.

Methods

The effect of cantharidin on breast cancer in vivo was evaluated by 4T1 mice model. Then the effects of cantharidin on TNBC cells was assessed by the MTT, colony formation, and AnnexinV-PE/7AAD staining. Cantharidin acts on EGFR were verified using the cell membrane chromatography, RT-PCR, Western blotting, MTT, and so on. Mechanistic studies were explored by dual-luciferase report assay, RT-PCR, western blotting, and immunofluorescence staining assay.

Results

Cantharidin inhibited TNBC cell growth and induce apoptosis by targeting EGFR. miR-607 was a novel EGFR regulator and exhibited suppressive functions on TNBC cell behaviors. Mechanistic study showed that cantharidin blocked the downstream PI3K/AKT/mTOR and ERK/MAPK signaling pathway.

Conclusion

Our results revealed that cantharidin may be served as a potential candidate for TNBC treatment by miR-607-mediated downregulation of EGFR.

Graphical Abstract
RAS signaling and immune cells: a sinister crosstalk in the tumor microenvironment
Authors: Liu Yongting , Xie Bin , Chen Qiong
Published: September 2023

The rat sarcoma virus (RAS) gene is the most commonly mutated oncogene in cancer, with about 19% of cancer patients carrying RAS mutations. Studies on the interaction between RAS mutation and tumor immune microenvironment (TIM) have been flourishing in recent years. More and more evidence has proved that RAS signals regulate immune cells' recruitment, activation, and differentiation while assisting tumor cells to evade immune surveillance. This review concluded the direct and indirect treatment strategies for RAS mutations. In addition, we updated the underlying mechanisms by which RAS signaling modulated immune infiltration and immune escape. Finally, we discussed advances in RAS-targeted immunotherapies, including cancer vaccines and adoptive cell therapies, with a particular focus on combination strategies with personalized therapy and great potential to achieve lasting clinical benefits.
Giant liposarcoma of esophagus: a rare case report
Authors: Li Qingjiao , Chen Si , Li Yanchun , Chen Zhihong , Liu Yu , Guo Wei
Published: September 2023

Background

Liposarcoma is a malignant mesenchymal tumor that most commonly involves the retroperitoneum and lower extremities. However, liposarcoma of esophagus has been rarely reported in the literature.

Case presentation

We report a case of a 46-year-old man with complaint of intermittent dysphagia for 6 years, accompanied with paroxysmal vomiting of pedicled tumor to the mouth. Imaging studies showed a huge mixed density lesion in the middle esophageal lumen. Surgical resection of the tumor was performed through an external cervical approach. Microscopically, the tumor was composed of mature adipocytes in normal adipose tissue prominently intersected by sparsely cellular fibrous septa containing atypical, enlarged spindle cells with hyperchromatic nuclei. Immunohistochemically, the tumor cells were positive for Vimentin, S-100, CD34 and MDM2. Besides, fluorescence in situ hybridization (FISH) analysis indicated the presence of amplification involving MDM2 gene. The patient was diagnosed as having esophageal well-differentiated liposarcoma and recovered well after the operation.

Conclusions

Esophageal liposarcoma is an extremely rare tumor. Due to the nonspecific clinical manifestation and lack of experience, it is challenging to make a clear diagnosis before operation. Definite diagnosis of esophageal liposarcoma depends on histopathology, immunohistochemistry and molecular analysis.
Fully automated volumetric modulated arc therapy planning for locally advanced rectal cancer: feasibility and efficiency
Authors: Hirotaki Kouta , Tomizawa Kento , Moriya Shunsuke , Oyoshi Hajime , Raturi Vijay , Ito Masashi , Sakae Takeji
Published: September 2023

Background

Volumetric modulated arc therapy (VMAT) for locally advanced rectal cancer (LARC) has emerged as a promising technique, but the planning process can be time-consuming and dependent on planner expertise. We aimed to develop a fully automated VMAT planning program for LARC and evaluate its feasibility and efficiency.

Methods

A total of 26 LARC patients who received VMAT treatment and the computed tomography (CT) scans were included in this study. Clinical target volumes and organs at risk were contoured by radiation oncologists. The automatic planning program, developed within the Raystation treatment planning system, used scripting capabilities and a Python environment to automate the entire planning process. The automated VMAT plan (auto-VMAT) was created by our automated planning program with the 26 CT scans used in the manual VMAT plan (manual-VMAT) and their regions of interests. Dosimetric parameters and time efficiency were compared between the auto-VMAT and the manual-VMAT created by experienced planners. All results were analyzed using the Wilcoxon signed-rank sum test.

Results

The auto-VMAT achieved comparable coverage of the target volume while demonstrating improved dose conformity and uniformity compared with the manual-VMAT. V30 and V40 in the small bowel were significantly lower in the auto-VMAT compared with those in the manual-VMAT (p < 0.001 and < 0.001, respectively); the mean dose of the bladder was also significantly reduced in the auto-VMAT (p < 0.001). Furthermore, auto-VMAT plans were consistently generated with less variability in quality. In terms of efficiency, the auto-VMAT markedly reduced the time required for planning and expedited plan approval, with 93% of cases approved within one day.

Conclusion

We developed a fully automatic feasible VMAT plan creation program for LARC. The auto-VMAT maintained target coverage while providing organs at risk dose reduction. The developed program dramatically reduced the time to approval.
Biotin-thiamine responsive basal ganglia disease: a retrospective review of the clinical, radiological and molecular findings of cases in Kuwait with novel variants
Authors: Aburezq Maryam , Alahmad Ahmad , Alsafi Rasha , Al-Tawari Asma , Ramadan Dina , Shafik Magdy , Abdelaty Omar , Makhseed Nawal , Elshafie Reem , Ayed Mariam , Hayat Abrar , Dashti Fatima , Marafi Dana , Albash Buthaina , Bastaki Laila , Alsharhan Hind
Published: September 2023

Background

Biotin-thiamine-responsive basal ganglia disease (BTBGD) is a rare autosomal recessive neurometabolic disorder that is caused by biallelic pathogenicSLC19A3variants and is characterized by subacute encephalopathy associated with confusion, convulsions, dysphagia, dysarthria, or other neurological manifestations.

Methods

A retrospective review of the data registry in Kuwait Medical Genetics Center for all cases diagnosed clinically and radiographically and confirmed genetically with BTBGD.

Results

Twenty one cases from 13 different families were diagnosed with BTBGD in Kuwait. Most cases (86%) presented with confusion, dystonia, convulsions, or dysarthria, while three individuals were diagnosed pre-symptomatically during familial targeted genetic screening. Symptoms resolved completely within 2-week of treatment in two-thirds of the symptomatic cases but progressed in six of them to a variety of severe symptoms including severe cogwheel rigidity, dystonia and quadriparesis due to delayed presentation and management. Neuroradiological findings of the symptomatic cases revealed bilateral central changes in the basal ganglia. Two novel homozygous missenseSLC19A3variants were detected in a Kuwaiti and a Jordanian individuals, in addition to the previously reported Saudi founder homozygous variant, c.1264A > G; p.(Thr422Ala) in the remaining cases. Age of diagnosis ranged from newborn to 32 years, with a median age of 2–3 years. All cases are still alive receiving high doses of biotin and thiamine.

Conclusion

This is the first study reporting the phenotypic and genotypic spectrum of 21 individuals with BTBGD in Kuwait and describing two novelSLC19A3variants. BTBGD is a treatable neurometabolic disease that requires early recognition and treatment initiation. This study highlights the importance of performing targeted molecular testing of the founder variant in patients presenting with acute encephalopathy in the region.
RNA binding protein IGF2BP1 synergizes with ETV6-RUNX1 to drive oncogenic signaling in B-cell Acute Lymphoblastic Leukemia
Authors: Sharma Gunjan , Tran Tiffany M. , Bansal Ishu , Beg Mohammad Sabique , Bhardwaj Ruchi , Bassi Jaspal , Tan Yuande , Jaiswal Amit Kumar , Tso Christine , Jain Ayushi , Singh Jay , Chattopadhyay Parthaprasad , Singh Archna , Chopra Anita , Bakhshi Sameer , Casero David , Rao Dinesh S. , Palanichamy Jayanth Kumar
Published: September 2023

Background

Acute lymphoblastic leukemia (ALL) is the most common pediatric hematological malignancy, with ETV6::RUNX1 being the most prevalent translocation whose exact pathogenesis remains unclear. IGF2BP1 (Insulin-like Growth Factor 2 Binding Protein 1) is an oncofetal RNA binding protein seen to be specifically overexpressed in ETV6::RUNX1 positive B-ALL. In this study, we have studied the mechanistic role of IGF2BP1 in leukemogenesis and its synergism with the ETV6::RUNX1 fusion protein.

Methods

Gene expression was analyzed from patient bone marrow RNA using Real Time RT-qPCR. Knockout cell lines were created using CRISPR-Cas9 based lentiviral vectors. RNA-Seq and RNA Immunoprecipitation sequencing (RIP-Seq) after IGF2BP1 pulldown were performed using the Illumina platform. Mouse experiments were done by retroviral overexpression of donor HSCs followed by lethal irradiation of recipients using a bone marrow transplant model.

Results

We observed specific overexpression of IGF2BP1 in ETV6::RUNX1 positive patients in an Indian cohort of pediatric ALL (n=167) with a positive correlation with prednisolone resistance.

IGF2BP1 expression was essential for tumor cell survival in multiple ETV6::RUNX1 positive B-ALL cell lines. Integrated analysis of transcriptome sequencing after IGF2BP1 knockout and RIP-Seq after IGF2BP1 pulldown in Reh cell line revealed that IGF2BP1 targets encompass multiple pro-oncogenic signalling pathways including TNFα/NFκB and PI3K-Akt pathways. These pathways were also dysregulated in primary ETV6::RUNX1 positive B-ALL patient samples from our center as well as in public B-ALL patient datasets. IGF2BP1 showed binding and stabilization of the ETV6::RUNX1 fusion transcript itself. This positive feedback loop led to constitutive dysregulation of several oncogenic pathways.

Enforced co-expression of ETV6::RUNX1 and IGF2BP1 in mouse bone marrow resulted in marrow hypercellularity which was characterized by multi-lineage progenitor expansion and strong Ki67 positivity. This pre-leukemic phenotype confirmed their synergism in-vivo. Clonal expansion of cells overexpressing both ETV6::RUNX1 and IGF2BP1 was clearly observed. These mice also developed splenomegaly indicating extramedullary hematopoiesis.

Conclusion

Our data suggest a combined impact of the ETV6::RUNX1 fusion protein and RNA binding protein, IGF2BP1 in activating multiple oncogenic pathways in B-ALL which makes IGF2BP1 and these pathways as attractive therapeutic targets and biomarkers.
Decreased vitamin D levels in the pediatric population after COVID-19 lockdown
Authors: Cavarzere Paolo , Pausilli Romina , Nicolussi Prinicpe Lara , Gaudino Rossella , Guzzo Alessandra , Cantalupo Gaetano , Antoniazzi Franco
Published: September 2023

Backgroud

SARS-Cov2 infection began to spread worldwide since December 2019; on March 2020, the World Health Organization characterized its related disease, named COVID-19, as a pandemic. In Italy, to contain the spread of infection a severe lockdown in the spring 2020 was instituted. Other less severe restrictions were imposed in the winter 2020–2021 and in the spring 2021. The containment measures caused a series of consequences for the population and, in particular, for children and adolescents that presented psychophysical problems.

The aim of this manuscript is to investigate the serum levels of vitamin D in children and adolescents before, during and after the lockdown consequent to COVID-19 pandemic.

Methods

This is a retrospective cross-sectional study, including all children and adolescents between 1 to 18 years referring to the Pediatric Endocrinology Service of the University Hospital of Verona, Italy, between January 2019 and December 2021. All patients affected by clinical conditions that involve vitamin D metabolism or assuming vitamin D supplementation were excluded.

Results

In total, 491 children (36.7% males and 63.3% females) were enrolled in this study. The vitamin D levels decreased over time: 28.3 ± 10.2 ng/mL in 2019; 28.2 ± 11.4 ng/mL in 2020 and 24.9 ± 10.1 ng/mL in 2021 (p < 0.05). The vitamin D levels are significant higher in summer and in autumn in comparison with the levels of winter and spring, regardless of the examined years.

Conclusions

The measures adopted to contain the COVID-19 pandemic led to a reduction of serum levels of vitamin D in pediatric population, probably due to the reduced solar exposure. This may have severe consequences on the bone metabolism of those children who did not present optimal vitamin D levels even before the lockdown. Therefore, an adequate supplementation of vitamin D is necessary from the end of fall to the beginning of spring (November–April) in all children and adolescents living in Northern Italy.
Impact of Covid-19 on risk of severe maternal morbidity
Authors: Auger Nathalie , Ukah U. Vivian , Wei Shu Qin , Healy-Profitós Jessica , Lo Ernest , Dayan Natalie
Published: September 2023

Background

We examined the risk of severe life-threatening morbidity in pregnant patients with Covid-19 infection.

Methods

We conducted a population-based study of 162,576 pregnancies between March 2020 and March 2022 in Quebec, Canada. The main exposure was Covid-19 infection, including the severity, period of infection (antepartum, peripartum), and circulating variant (wildtype, alpha, delta, omicron). The outcome was severe maternal morbidity during pregnancy up to 42 days postpartum. We estimated risk ratios (RR) and 95% confidence intervals (CI) for the association between Covid-19 infection and severe maternal morbidity using adjusted log-binomial regression models.

Results

Covid-19 infection was associated with twice the risk of severe maternal morbidity compared with no infection (RR 2.02, 95% CI 1.76–2.31). Risks were elevated for acute renal failure (RR 3.01, 95% CI 1.79–5.06), embolism, shock, sepsis, and disseminated intravascular coagulation (RR 1.35, 95% CI 0.95–1.93), and severe hemorrhage (RR 1.49, 95% CI 1.09–2.04). Severe antepartum (RR 13.60, 95% CI 10.72–17.26) and peripartum infections (RR 20.93, 95% CI 17.11–25.60) were strongly associated with severe maternal morbidity. Mild antepartum infections also increased the risk, but to a lesser magnitude (RR 3.43, 95% CI 2.42–4.86). Risk of severe maternal morbidity was around 3 times greater during circulation of wildtype and the alpha and delta variants, but only 1.2 times greater during omicron.

Conclusions

Covid-19 infection during pregnancy increases risk of life-threatening maternal morbidity, including renal, embolic, and hemorrhagic complications. Severe Covid-19 infection with any variant in the antepartum or peripartum periods all increase the risk of severe maternal morbidity.
Comparison of three regimens with inhalational methoxyflurane versus intranasal fentanyl versus intravenous morphine in pre-hospital acute pain management: study protocol for a randomized controlled trial (PreMeFen)
Authors: Simensen Randi , Fjose Lars Olav , Rehn Marius , Hagemo Jostein , Thorsen Kjetil , Heyerdahl Fridtjof
Published: September 2023

Background

Pre-hospital pain management has traditionally been performed with intravenous (IV) morphine, but oligoanalgesia remain a recognized problem. Pain reduction is essential for patient satisfaction and is regarded as a measure of successful treatment. We aim to establish whether non-invasive methods such as inhalation of methoxyflurane is non-inferior to intranasal fentanyl or non-inferior to the well-known IV morphine in the pre-hospital treatment of acute pain.

Method/design

The PreMeFen study is a phase three, three-armed, randomized, controlled, non-inferiority trial to compare three regimens of analgesics: inhalation of methoxyflurane and intranasal (IN) fentanyl versus IV morphine. It is an open-label trial with a 1:1:1 randomization to the three treatment groups. The primary endpoint is the change in pain numeric rating scale (NRS) (0–10) from baseline to 10 min after start of investigational medicinal product administration (IMP). The non-inferiority margin was set to 1.3, and a sample size of 270 patients per protocol (90 in each treatment arm) will detect this difference with 90% power.

Discussion

We chose a study design with comparison of analgesic regimens rather than fixed doses because of the substantial differences in drug characteristics and for the results to be relevant to inform policymakers in the pre-hospital setting. We recognize that easier administration of analgesics will lead to better pain management for many patients if the regimens are as good as the existing, and hence, we chose a non-inferiority design. The primary endpoint, the change in pain (NRS) after 10 min, is set to address the immediate need of pain reduction for patients with acute prehospital pain. On a later stage, more analgesic methods are often available.

PreMeFen is a non-inferiority randomized controlled trial comparing three analgesic regimens aiming to establish whether inhalation of methoxyflurane or intranasal fentanyl is as good as IV morphine for fast reduction of acute pain in the prehospital setting.
LogD7.4 prediction enhanced by transferring knowledge from chromatographic retention time, microscopic pKa and logP
Authors: Wang Yitian , Xiong Jiacheng , Xiao Fu , Zhang Wei , Cheng Kaiyang , Rao Jingxin , Niu Buying , Tong Xiaochu , Qu Ning , Zhang Runze , Wang Dingyan , Chen Kaixian , Li Xutong , Zheng Mingyue
Published: September 2023

Lipophilicity is a fundamental physical property that significantly affects various aspects of drug behavior, including solubility, permeability, metabolism, distribution, protein binding, and toxicity. Accurate prediction of lipophilicity, measured by the logD7.4 value (the distribution coefficient between n-octanol and buffer at physiological pH 7.4), is crucial for successful drug discovery and design. However, the limited availability of data for logD modeling poses a significant challenge to achieving satisfactory generalization capability. To address this challenge, we have developed a novel logD7.4 prediction model called RTlogD, which leverages knowledge from multiple sources. RTlogD combines pre-training on a chromatographic retention time (RT) dataset since the RT is influenced by lipophilicity. Additionally, microscopic pKa values are incorporated as atomic features, providing valuable insights into ionizable sites and ionization capacity. Furthermore, logP is integrated as an auxiliary task within a multitask learning framework. We conducted ablation studies and presented a detailed analysis, showcasing the effectiveness and interpretability of RT, pKa, and logP in the RTlogD model. Notably, our RTlogD model demonstrated superior performance compared to commonly used algorithms and prediction tools. These results underscore the potential of the RTlogD model to improve the accuracy and generalization of logD prediction in drug discovery and design. In summary, the RTlogD model addresses the challenge of limited data availability in logD modeling by leveraging knowledge from RT, microscopic pKa, and logP. Incorporating these factors enhances the predictive capabilities of our model, and it holds promise for real-world applications in drug discovery and design scenarios.

Graphical Abstract
Social equity perception and public mental health: a Chinese study with panel data
Authors: Yang Fan , Jiang Yao , Bai Xiu , Cai Yuchen , Duan Haiying
Published: September 2023

Background

Mental health is a vital part of an individual’s overall health and well-being, and the relationship between society and individuals has always been a focus of academic and public attention. However, the effect of social equity perceptions on individual mental health remains unclear.

Methods

Data were collected from 8,922 survey respondents with an average age of 47.533 years from the China Labor-force Dynamics Survey 2016 and 2018. The Center for Epidemiological Studies Depression scale was used to assess mental health. A two-way fixed effects regression model was used to determine the association between social equity perception and individual mental health.

Results

Individuals with higher perceptions of social equity were more likely to report better mental health ($$\beta$$
β
= -0.944, p < 0.01). Happiness, life satisfaction, and social trust partially play mediating roles in the relationship between social equity perception and individual mental health, while education and age play moderating roles.

Conclusion

Social equity perception is a vital factor that affects mental health. Public policies should focus on helping less educated and older people improve their social equity perception to improve their mental health.
Burden of end-stage renal disease of undetermined etiology in Africa
Authors: Fiseha Temesgen , Osborne Nicholas J.
Published: September 2023

In the last two decades, there have been increasing recognition of excess cases of end-stage renal disease (ESRD) requiring renal replacement therapy without common underlying causes (diabetes, hypertension, glomerulonephritis, or any identifiable cause) in many parts of low-to-middle income countries. ESRD of unknown etiology mainly affects young working-age adults and is a global health problem with substantial morbidity, mortality and disability. In this review, we provide a comprehensive overview of the burden and outcomes of treated ESRD attributable to unknown etiology in African countries. Estimates indicate that up to 71% of adults and up to 53% children on dialysis suffer from ESRD due to unknown etiology. ESRD of unknown etiology affects mostly the economically productive young adults, males and those from rural areas. ESRD due to unknown etiology carries an almost twofold risk of mortality compared to traditional ESRD causes and account for up to 55% of the renal medical admissions burden. This review confirms that treated ESRD due to unknown etiology is a major public health issue in Africa. Future studies are urgent need for better characterizing the regional causative factors as well as for developing proactive and comprehensive approaches to prevent and treat this under-recognized disease.
Risk of pneumonia in the vicinity of goat farms: a comparative assessment of temporal variation based on longitudinal health data
Authors: Yzermans C. Joris , Moleman Youri P. , Spreeuwenberg Peter , Nielen Mark M.J. , Dückers Michel L.A. , Smit Lidwien A.M. , Baliatsas Christos
Published: September 2023

Background

Although the association between living in the vicinity of a goat farm and the occurrence of pneumonia is well-documented, it is unclear whether the higher risk of pneumonia in livestock dense areas is season-specific or not. This study explored the temporal variation of the association between exposure to goat farms and the occurrence of pneumonia.

Methods

A large population-based study was conducted in the Netherlands, based on electronic health records from 49 general practices, collected for a period of six consecutive years (2014–2019). Monthly incidence rates of pneumonia in a livestock dense area were compared with those of a control group (areas with low livestock density) both per individual year and cumulatively for the entire six-year period. Using individual estimates of livestock exposure, it was also examined whether incidence of pneumonia differed per month if someone lived within a certain radius from a goat farm, compared to residents who lived further away.

Results

Pneumonia was consistently more common in the livestock dense area throughout the year, compared to the control area. Analyses on the association between the individual livestock exposure estimates and monthly pneumonia incidence for the whole six-year period, yielded a generally higher risk for pneumonia among people living within 500 m from a goat farm, compared to those living further away. Significant associations were observed for March (IRR 1.68, 95% CI 1.02–2.78), August (IRR 2.67, 95% CI 1.45–4.90) and September (IRR 2.52, 95% CI 1.47–4.32).

Conclusions

The increased occurrence of pneumonia in the vicinity of goat farms is not season-specific. Instead, pneumonia is more common in livestock dense areas throughout the year, including summer months.
Opinion dynamics of improved Hegselmann-Krause model with agent's stubbornness and stubborn agents
Authors: Wang Na , Rong Zhihai , Yang Wen
Published: September 2023

In this work, we improve the Hegselmann-Krause model (HK model) by combining the agent's stubbornness and the quantitative impact of stubborn agents on the evolution of other agents’ opinions. We divide stubborn agents into expert stubborn agents, environmentally stubborn agents and intrinsically stubborn agents based on the impact weight and agent's characteristics. We simulate the evolution of opinions of the improved HK model, and find that it is closer to reality. We also study the impact of the influence coefficient and the proportion of intrinsically stubborn agents on the stabilization time, and find that the presence of non-expert stubborn agents reduces the rate of convergence of opinions. Finally, we verify the effectiveness of the improved HK model by two real social events.
Phase transitions in systems of particles with only hard-core interactions
Authors: Dhar Deepak , Rajesh R. , Kumar Aanjaneya
Published: September 2023

This article contains our comments and views on the status of the current understanding of phase transitions in systems in thermodynamic equilibrium with only hard-core interactions, based on our work in this area. The equation of state for the hard sphere gas in d-dimensions is discussed. The universal repulsive Lee-Yang singularity in the complex activity plane, and its relation to the directed and undirected polymer models are outlined. We also discuss orientationally disordered crystalline mesophases, and some of their models.
An Applied Anatomic Guide to Anterior Temporal Lobectomy and Amygdalohippocampectomy: Laboratory Cranial and White Matter Dissections to Inform Surgical Practice
Authors: Charalampopoulou Eirini , Neromyliotis Eleftherios , Anastasopoulos Lykourgos , Komaitis Spyridon , Drosos Evangelos , Skandalakis Georgios P. , Kalyvas Aristotelis V. , Stranjalis George , Koutsarnakis Christos
Published: September 2023

BACKGROUND AND OBJECTIVES:

Anterior temporal lobectomy and amygdalohippocampectomy is a challenging procedure because of the deep surgical trajectory and complex regional neurovascular anatomy. A thorough knowledge of the involved anatomic structures is crucial for a safe and effective procedure. Our objective is to explore the white matter pathways in or around the operative corridor and to illuminate the 3-dimensional relationships of the pertinent operative parenchymal and skull base anatomy, aiming to inform and simplify surgical practice.

METHODS:

Four normal, adult, cadaveric, formalin-fixed cerebral hemispheres (2 left and 2 right) treated with the Klinger's technique and 2 formalin-fixed and colored-latex–injected cadaveric heads (4 sides) were used. Focused white matter and cadaveric dissections were used to study the relevant anatomy implicated during an anterior temporal lobectomy. Four illustrative cases were also included. Digital photographs from every dissection step were obtained.

RESULTS:

Major white matter pathways that are inevitably traversed during the approach are the inferior longitudinal fasciculus, uncinate fasciculus, and inferior arm of the cingulum. Tracts that can be potentially injured, should the dissection plane tilt inadvertently superiorly or posteriorly, are the inferior fronto-occipital fasciculus, Meyer's loop, superior longitudinal fasciculus/arcuate fasciculus complex, and basal ganglia. Consistent cranial and parenchymal landmarks that can act as a roadmap during the procedure are recorded and paired with their intraoperative equivalent to provide a thorough, yet simple, stepwise guide for the surgeon.

CONCLUSION:

White matter dissections, cadaveric cranial dissections, and intraoperative images are put together to provide a simplified stepwise surgical manual for anterior temporal lobectomy. Laboratory investigations that focus on the intricate 3-dimensional relationships of the pertinent operative anatomy from the surgeon's eye may enrich anatomic knowledge and push surgical boundaries, to minimize complication rates and ultimately improve patient outcomes.
Global and local functions of the Fused kinase ortholog CdaH in intracellular patterning in Tetrahymena
Authors: Lee Chinkyu , Maier Wolfgang , Jiang Yu-Yang , Nakano Kentaro , Lechtreck Karl F. , Gaertig Jacek
Published: September 2023

Ciliates assemble numerous microtubular structures into complex cortical patterns. During ciliate division, the pattern is duplicated by intracellular segmentation that produces a tandem of daughter cells. In Tetrahymena thermophila, the induction and positioning of the division boundary involves two mutually antagonistic factors: posterior CdaA (cyclin E) and anterior CdaI (Hippo kinase). Here, we characterized the related cdaH-1 allele, which confers a pleiotropic patterning phenotype including an absence of the division boundary and an anterior–posterior mispositioning of the new oral apparatus. CdaH is a Fused or Stk36 kinase ortholog that localizes to multiple sites that correlate with the effects of its loss, including the division boundary and the new oral apparatus. CdaH acts downstream of CdaA to induce the division boundary and drives asymmetric cytokinesis at the tip of the posterior daughter. CdaH both maintains the anterior–posterior position of the new oral apparatus and interacts with CdaI to pattern ciliary rows within the oral apparatus. Thus, CdaH acts at multiple scales, from induction and positioning of structures on the cell-wide polarity axis to local organelle-level patterning.
Multi-organ Radiomics-Based Prediction of Future Remnant Liver Hypertrophy Following Portal Vein Embolization
Authors: Gerwing Mirjam , Schindler Philipp , Katou Shadi , Köhler Michael , Stamm Anna Christina , Schmidt Vanessa Franziska , Heindel Walter , Struecker Benjamin , Morgul Haluk , Pascher Andreas , Wildgruber Moritz , Masthoff Max
Published: September 2023

Background

Portal vein embolization (PVE) is used to induce remnant liver hypertrophy prior to major hepatectomy. The purpose of this study was to evaluate the predictive value of baseline computed tomography (CT) data for future remnant liver (FRL) hypertrophy after PVE.

Methods

In this retrospective study, all consecutive patients undergoing right-sided PVE with or without hepatic vein embolization between 2018 and 2021 were included. CT volumetry was performed before and after PVE to assess standardized FRL volume (sFRLV). Radiomic features were extracted from baseline CT after segmenting liver (without tumor), spleen and bone marrow. For selecting features that allow classification of response (hypertrophy ≥ 1.33), a stepwise dimension reduction was performed. Logistic regression models were fitted and selected features were tested for their predictive value. Decision curve analysis was performed on the test dataset.

Results

A total of 53 patients with liver tumor were included in this study. sFRLV increased significantly after PVE, with a mean hypertrophy of FRL of 1.5 ± 0.3-fold. sFRLV hypertrophy ≥ 1.33 was reached in 35 (66%) patients. Three independent radiomic features, i.e. liver-, spleen- and bone marrow-associated, differentiated well between responders and non-responders. A logistic regression model revealed the highest accuracy (area under the curve 0.875) for the prediction of response, with sensitivity of 1.0 and specificity of 0.5. Decision curve analysis revealed a positive net benefit when applying the model.

Conclusions

This proof-of-concept study provides first evidence of a potential predictive value of baseline multi-organ radiomics CT data for FRL hypertrophy after PVE.
Χρήση νεότερων βιοδεικτών στην πνευμονία που σχετίζεται με τον αναπνευστήρα σε διασωληνωμένα βαρέως πάσχοντα παιδιά
Authors: Σδούγκα Μαρία
Published: September 2023

Εισαγωγή: Πρόκειται για την πρώτη ερευνητική πιλοτική μελέτη σε πανελλήνιο επίπεδο, η οποία προστέθηκε στη διεθνή βιβλιογραφία και αφορά στη διαγνωστική προσέγγιση της VAP σε διασωληνωμένα βαρέως πάσχοντα παιδιά, νοσηλευόμενα σε Μονάδα Εντατικής Παίδων. Ο σκοπός της μελέτης ήταν η ανίχνευση νεότερων βιοδεικτών στον ορό αίματος και στις βρογχικές εκκρίσεις, αναζητώντας τη συσχέτισή τους με την εμφάνιση και την έκβαση της νόσου. Η έγκαιρη διάγνωση της VAP αποτελεί πρόκληση για τον κλινικό ιατρό, λόγω των υποκειμενικών κλινικών κριτηρίων και της χαμηλής διακριτικής ισχύος των διαγνωστικών εξετάσεων. Μεθοδολογία: Αρχικά καθορίστηκαν τα κριτήρια ένταξης και αποκλεισμού των ασθενών στη μελέτη. Ακολούθησε καταγραφή των δημογραφικών και κλινικών χαρακτηριστικών. Σύμφωνα με την τροπο-ποιημένη κλίμακα για παιδιά του Κλινικού Πνευμονικού Δείκτη (mCPIS), οι ασθενείς κατηγοριοποιήθηκαν σε δύο ομάδες: με υψηλή υποψία VAP και χαμηλή υποψία VAP. Συλλέχθηκαν δείγματα ορού αίματος και βρογχικών εκκρίσεων κατά τις ημέρες 1η, 3η, 6η και 12η από την ένταξη στη μελέτη. Χρησιμοποιήθηκε μοριακή πλατφόρμα ταχείας διάγνωσης για την ταυτοποίηση των παθογόνων του αναπνευστικού και η μέθοδος ELISA για τη μέτρηση επιπέδων των βιοδεικτών PTX-3, SPD, sTREM-1, IL-1β IL-4, IL-8, PAI-1 και RAGE.Αποτελέσματα: Από τους 20 ασθενείς που εντάχθηκαν στη μελέτη, οι 12 ήταν υψηλής υποψίας VAP (mCPIS ≥ 6) με διάμεση ηλικία 24,5 (6-141) μήνες και οι 8 χαμηλής υποψίας VAP (mCPIS < 6) με διάμεση ηλικία 129 (28-184) μήνες. Το 65% ήταν αγόρια και το 35% είχαν υποκείμενο νόσημα. Τα επίπεδα IL-1β κατά την 1η ημέρα παρουσίασαν στατιστικά σημαντική συσχέτιση με τις ημέρες μηχανικού αερισμού (r = 0.67, p < 0.01) και τη διάρκεια παραμονής στη ΜΕΘ (r = 0.66, p < 0.02). Δεν σημειώθηκε στατιστικά σημαντική διαφορά στα επίπεδα των λοιπών βιοδεικτών μεταξύ των δύο ομάδων (p > 0.05). Η ταυτόχρονη μέτρηση των βιοδεικτών PTX3 και SPD στον ορό αίματος και στις βρογχικές εκκρίσεις κατέδειξε κατανομή της PTX3 κυρίως στον ορό αίματος σε αντίθεση με τον SPD που είχε ταυτόχρονη κατανομή τόσο στον ορό αίματος όσο και στις βρογχικές εκκρίσεις. Δύο ασθενείς από την ομάδα υψηλής υποψίας VAP κατέληξαν, ο πρώτος λόγω σηπτικής καταπληξίας την 3η ημέρα από την ένταξη στη μελέτη και ο δεύτερος 30 ημέρες από την ένταξη στη μελέτη και μετά την έξοδό του από τη Μονάδα, λόγω καρδιακής ανακοπής. Συμπεράσματα: Η έλλειψη ενός “gold standard” διαγνωστικού εργαλείου για την VAP στους διασωληνωμένους ασθενείς των ΜΕΘ Παίδων συνεπάγεται την περαιτέρω έρευνα. Κρίνεται αναγκαία η διεξαγωγή πολυκεντρικών μελετών των νεότερων βιοδεικτών, με επικέντρωση στη διάγνωση, την πορεία και την έκβαση της νόσου.
Evolución del Perfil de los Políticos Andaluces en 40 años de Autonomía Regional (1982-2022).
Authors: Benítez Andrés , Carrasco Beatriz
Published: September 2023

Este artículo analiza el perfil social de los representantes políticos andaluces con el objetivo de dar respuesta a cómo son y cuál ha sido la evolución de su perfil sociodemográfico desde 1982 a 2022. La metodología aplica el análisis estadístico a la base de datos BAPOLDATA que incluye a todas las personas que han ocupado un escaño en el Congreso de los Diputados y en las 17 cámaras autonómicas desde la legislatura constituyente. También se realiza una comparación del perfil de aquellos parlamentarios/as que han ocupado un escaño en el Parlamento de Andalucía y entre quienes han poseído el acta de diputado en el Congreso de los Diputados por las circunscripciones andaluzas, mostrando que actualmente, el Parlamento de Andalucía está más envejecido, con un mayor nivel de estudios y con representación femenina en torno al 50%. En cuanto a las profesiones, han prácticamente desaparecido los trabajadores manuales y pasado a predominar los docentes y juristas.
Evaluando el Cumplimiento de Promesas Electorales. El caso de PSOE-Unidas Podemos, año 2020 .
Authors: Bandera Noel
Published: September 2023

Los programas electorales de los partidos gobernantes se pueden considerar un compromiso con la ciudadanía. El objetivo de esta investigación es diseñar una metodología para evaluar el cumplimiento de los programas de los partidos políticos y aplicarla evaluando el nivel alcanzado en el primer año de legislatura, enero a diciembre 2020, del cumplimiento de (los 200 puntos) del acuerdo de coalición de gobierno entre los partidos PSOE y Unidas Podemos, en España. La metodología diseñada y aplicada se apoya en la recogida de documentación publicada en medios y fuentes oficiales acerca de cada medida a lo largo del año del análisis y puntuar de 0 a 10 los avances alcanzados. Los resultados se comparan con las otras 2 evaluaciones existentes: la del propio Gobierno y la de Newtral (referida a la mitad de los compromisos). En conclusión, tras un año de legislatura, el cumplimiento de programa alcanzó un 19,6% según nuestros resultados; mientras que los estudios de Newtral y presidencia del Gobierno estimaron un avance mayor y similar entre sí.
La necesidad de regular las actividades de "lobbying" en España: Un camino hacia la estandarización de la transparencia.
Authors: Arceo Vacas Alfredo , Álvarez Sánchez Sergio
Published: September 2023

Se denomina lobbying a la realización de acciones por parte de grupos de interés para influir en las decisiones políticas de los agentes públicos. Esta práctica es un campo de las relaciones públicas, en tanto que requiere del diálogo con los representantes de las instituciones. Tradicionalmente, se ha visto asociada a la opacidad, contra la que se empezaba a luchar en España con el reciente anteproyecto de Ley de Transparencia de los Grupos de Interés, el cual ha quedado paralizado ante el adelanto electoral de julio de 2023. Aunque las carencias regulatorias convierten al lobbying en una materia de difícil estudio, se han señalado como factores de la capacidad de influencia de un lobby: el número de miembros con los que cuente; su antigüedad; su capacidad económica; el tipo de intereses que defiende, y su grado de especialización. También sobresalen la participación en comités públicos, el número de empleados y la práctica de lobbying indirecto. La estandarización de los esfuerzos de transparencia de los lobbies españoles, incluyendo su autorregulación, será vital para aceptarlos como legítimos participantes en la esfera pública, beneficiándose igualmente de contar con representantes en Bruselas y con estructuras internas especializadas.
Nadzieja znaleziona w przeszłości. XVIII-wieczna parenetyka na przykładzie biografistyki staropolskiej
Authors: Kurkowski Mateusz
Published: September 2023

In this article, the author focuses on Old Polish biography in the 18th century, and more specifically on its social impact in both the short and long term. The author draws attention to the literary uniqueness of the genre of biography in history and tries to explain why it was so popular at that time. The use of biography in paraenesis is an interesting case of the meeting point between history and literature, and this is what the author focuses on. In addition, the author draws attention to the possibility of the existence of a catalog of national heroes, which was created at that time on the pages of biographies and has remained in use to this day.
Partykularyzm litewski na przykładzie konwokacji w Białej i Grodnie w 1665 roku
Authors: Byrski Albert
Published: September 2023

The end of the reign of John II Casimir Vasa was an extremely turbulent period in the history of the Polish-Lithuanian Commonwealth, during which mutual Polish-Lithuanian relations escalated. One of the problems in research conducted on this period is Lithuanian particularism. Although it has been well researched in the era of the Union of Lublin and the first half of the 17th century, there is a lack of thorough analysis of the second half the 17th century. This article aims to present Lithuanians' actions (and their nature) in the Polish-Lithuanian Commonwealth in the declining period of the reign of John II Casimir Vasa on the example of the two convocations in Biała and Grodno in 1665. The text primarily focuses on analyzing the problem in the light of propaganda and parliamentary practice, thus presenting a dualistic picture of the above-mentioned actions. The paper also explains the determinants of the perception of the events by both political ‘nations’ and formulates a detailed definition of particularism for the 1660s. The paper is based on the published political writings of the period in question, the published diary of Jan Antoni Chrapowicki, and the well-developed literature on parliamentarism and political struggle in both Lithuania and the Polish-Lithuanian Commonwealth.