bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.

Summary
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

AbstractLipophilicity 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

Abstract
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

AbstractIn 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

Abstract
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

Abstract
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

Abstract
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

ABSTRACT
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.