bluuebunny/crossref_metadata_2025_split huggingface dataset:
AAA237, an SKP2 inhibitor, suppresses glioblastoma by inducing BNIP3-dependent autophagy through the mTOR pathway
Authors: Zhang Yizhi , Li Wan , Yang Yihui , Zhang Sen , Yang Hong , Hao Yue , Fang Xu , Du Guanhua , Shi Jianyou , Wu Lianqiu , Wang Jinhua 
Published: February 2024

Abstract
Background
Glioblastoma (GBM) is the most common brain tumor with the worst prognosis. Temozolomide is the only first-line drug for GBM. Unfortunately, the resistance issue is a classic problem. Therefore, it is essential to develop new drugs to treat GBM. As an oncogene, Skp2 is involved in the pathogenesis of various cancers including GBM. In this study, we investigated the anticancer effect of AAA237 on human glioblastoma cells and its underlying mechanism.

Methods
CCK-8 assay was conducted to evaluate IC50 values of AAA237 at 48, and 72 h, respectively. The Cellular Thermal Shift Assay (CETSA) was employed to ascertain the status of Skp2 as an intrinsic target of AAA237 inside the cellular milieu. The EdU-DNA synthesis test, Soft-Agar assay and Matrigel assay were performed to check the suppressive effects of AAA237 on cell growth. To identify the migration and invasion ability of GBM cells, transwell assay was conducted. RT-qPCR and Western Blot were employed to verify the level of BNIP3. The mRFP-GFP-LC3 indicator system was utilized to assess alterations in autophagy flux and investigate the impact of AAA237 on the dynamic fusion process between autophagosomes and lysosomes. To investigate the effect of compound AAA237 on tumor growth in vivo, LN229 cells were injected into the brains of mice in an orthotopic model.

Results
AAA237 could inhibit the growth of GBM cells in vitro. AAA237 could bind to Skp2 and inhibit Skp2 expression and the degradation of p21 and p27. In a dose-dependent manner, AAA237 demonstrated the ability to inhibit colony formation, migration, and invasion of GBM cells. AAA237 treatment could upregulate BNIP3 as the hub gene and therefore induce BNIP3-dependent autophagy through the mTOR pathway whereas 3-MA can somewhat reverse this process. In vivo, the administration of AAA237 effectively suppressed the development of glioma tumors with no side effects.

Conclusion
Compound AAA237, a novel Skp2 inhibitor, inhibited colony formation, migration and invasion of GBM cells in a dose-dependent manner and time-dependent manner through upregulating BNIP3 as the hub gene and induced BNIP3-dependent autophagy through the mTOR pathway therefore it might be a viable therapeutic drug for the management of GBM.

Graphical Abstract
Association between maternal blood or cord blood metal concentrations and catch-up growth in children born small for gestational age: an analysis by the Japan environment and children’s study
Authors: Takatani Tomozumi , Takatani Rieko , Eguchi Akifumi , Yamamoto Midori , Sakurai Kenichi , Taniguchi Yu , Kobayashi Yayoi , Mori Chisato , Kamijima Michihiro ,   the Japan Environment and Children’s Study Group
Published: February 2024

Abstract
Background
Catch-up growth issues among children born small for gestational age (SGA) present a substantial public health challenge. Prenatal exposure to heavy metals can cause adverse effects on birth weight. However, comprehensive studies on the accurate assessment of individual blood concentrations of heavy metals and their effect on the failure to achieve catch-up growth remain unavailable. This study aimed to evaluate the effects of uterine exposure to toxic metals cadmium, lead, and mercury and essential trace metals manganese and selenium at low concentrations on the postnatal growth of children born SGA.

Methods
Data on newborn birth size and other factors were obtained from the medical record transcripts and self-administered questionnaires of participants in the Japan Environment and Children’s Study. The blood concentrations of lead, cadmium, mercury, selenium, and manganese in pregnant women in their second or third trimester were determined by inductively coupled plasma mass spectrometry. These heavy metal concentrations were also assessed in pregnant women’s cord blood. Furthermore, the relationship between each heavy metal and height measure/catch-up growth in SGA children aged 4 years was analyzed using linear and logistic regression methods. These models were adjusted for confounders.

Results
We studied 4683 mother–child pairings from 103,060 pregnancies included in the Japan Environment and Children’s Study. Of these, 278 pairs were also analyzed using cord blood. At 3 and 4 years old, 10.7% and 9.0% of children who were born below the 10th percentile of body weight had height standard deviation scores (SDSs) below 2, respectively. Cord blood cadmium concentrations were associated with the inability to catch up in growth by 3 or 4 years old and the height SDS at 3 years old. In maternal blood, only manganese was positively associated with the height SDS of SGA children aged 2 years; however, it was not significantly associated with catch-up growth in these children.

Conclusion
Cadmium exposure is associated with failed catch-up development in SGA children. These new findings could help identify children highly at risk of failing to catch up in growth, and could motivate the elimination of heavy metal (especially cadmium) pollution to improve SGA children’s growth.
Joint association of physical activity and diet quality with dyslipidemia: a cross-sectional study in Western China
Authors: Mutalifu Munire , Zhao Qian , Wang Ying , Hamulati Xieyire , Wang Yu-Shan , Deng Lei , Adili Niyaziaili , Liu Fen , Yang Yi-Ning , Li Xiao-Mei 
Published: February 2024

Abstract
Objective
This study aims to investigate the prevalence of dyslipidemia and assess the joint association of physical activity (PA) and diet quality on dyslipidemia risk in urban areas of Xinjiang.

Methods
Conducted from July 2019 to September 2021 in Xinjiang, China, this cross-sectional study involved 11,855 participants (mean age 47.1 ± 9.4 years, 53.1% male). Standard methods were used to measure plasma cholesterol levels, and validated questionnaires were employed to evaluate dietary habits and PA. The definition of dyslipidemia is based on 2023 Chinese guidelines for lipid management. PA was divided into guideline-recommended moderate-to-vigorous physical activity (MVPA) and non-MVPA, following World Health Organization guidelines. The Food Frequency Questionnaire was used to obtain the intake frequency of each dietary term. Each item was scored based on consumption frequency and divided into three groups (good, intermediate, and poor) based on total dietary score. Multivariate logistic regression analysis was performed to identify dyslipidemia risk factors, as well as the joint association of PA and diet quality.

Results
Dyslipidemia prevalence among urban adults in Xinjiang was 39.3%, with notable sex disparities (52.6% in males vs. 24.3% in females, P < 0.001). Among participants with dyslipidemia, the awareness, treatment and control rates were 6.9%, 3.1%, and 1.9%, respectively. A significant multiplicative interaction between PA and diet quality is associated with dyslipidemia (P for interaction < 0.05). Less PA and poor diet quality were associated with an increased odds of dyslipidemia. Even individuals with poor (OR = 1.464, 95% CI: 1.106–1.939) or intermediate (OR = 1.229, 95% CI: 1.003–1.505) diet quality but adhering to recommended MVPA had lower odds of dyslipidemia compared to those with good diet quality but inadequate MVPA (OR = 1.510, 95% CI: 1.252–1.821).

Conclusions
Dyslipidemia prevalence was 39.3% in urban adults in Xinjiang, with limited awareness, treatment, and control. Following guideline-recommended MVPA and maintaining good diet quality were protective against dyslipidemia. Low levels of PA associated with a higher prevalence of dyslipidemia, even in individuals with good diet quality.
Harm reduction workforce, behavioral health, and service delivery in the USA: a cross-sectional study
Authors: de Saxe Zerden Lisa , Ware Orrin D. , Lombardi Brooke N. , Lombardi Brianna M. 
Published: February 2024

Abstract
Background
Despite recent financial and policy support for harm reduction in the USA, information on the types of workers within organizations who design, implement, and actualize harm reduction services remains nascent. Little is known about how variability in the harm reduction workforce impacts referrals and linkages to other community supports. This exploratory mixed-methods study asked: (1) Who constitutes the harm reduction workforce? (2) Who provides behavioral health services within harm reduction organizations? (3) Are referral services offered and by whom? (4) Do referrals differ by type of harm reduction worker?

Methods
Purposive sampling techniques were used to distribute an electronic survey to U.S.-based harm reduction organizations. Descriptive statistics were conducted. Multivariate binary logistic regression models examined the associations (a) between the odds of the referral processes at harm reduction organizations and (b) between the provision of behavioral health services and distinct types of organizational staff. Qualitative data were analyzed using a hybrid approach of inductive and thematic analysis.

Results
Data from 41 states and Washington, D.C. were collected (N = 168; 48% response rate). Four primary types of workers were identified: community health/peer specialists (87%); medical/nursing staff (55%); behavioral health (49%); and others (34%). About 43% of organizations had a formal referral process; among these, only 32% had follow-up protocols. Qualitative findings highlighted the broad spectrum of behavioral health services offered and a broad behavioral health workforce heavily reliant on peers. Unadjusted results from multivariate models found that harm reduction organizations were more than 5 times more likely (95% CI [1.91, 13.38]) to have a formal referral process and 6 times more likely (95% CI [1.74, 21.52]) to have follow-up processes when behavioral health services were offered. Organizations were more than two times more likely (95% CI [1.09, 4.46]) to have a formal referral process and 2.36 (95% CI [1.11, 5.0]) times more likely to have follow-up processes for referrals when behavioral health providers were included.

Conclusions
The composition of the harm reduction workforce is occupationally diverse. Understanding the types of services offered, as well as the workforce who provides those services, offers valuable insights into staffing and service delivery needs of frontline organizations working to reduce morbidity and mortality among those who use substances. Workforce considerations within U.S.-based harm reduction organizations are increasingly important as harm reduction services continue to expand.
Factors associated with gaps in naloxone knowledge: evidence from a 2022 great plains survey
Authors: Cooper-Ohm Spencer , Habecker Patrick , Humeniuk Ryan , Bevins Rick A. 
Published: February 2024

Abstract
Background
The rising prevalence of fast-acting opioids in the USA suggests the increased need for non-professional first responder administration of naloxone. Effective administration of naloxone during an overdose requires that bystanders are familiar with, have access to, and know how to use naloxone.

Methods
Drawing on a statewide, address-based sample of Nebraskan adults, we used logistic regression to predict the likelihood of respondents’ familiarity with, access to, and competency to administer naloxone. Our independent variables included measures indicating proximity to drug use, perceived community stigma toward people who use drugs, and demographic data.

Results
There were significant gaps in naloxone knowledge in Nebraska. Although 74.8% of respondents were familiar with naloxone, only 18.2% knew how to access it and 18.0% knew how to use it. Being close to an overdose experience, lifetime illicit opioid use, being close to a person who uses opioids, and having access to illicit opioids were not significantly associated with naloxone familiarity, access, or competency among respondents in Nebraska’s two largest cities, Omaha and Lincoln. Outside of these cities, being close to a past overdose experience and access to illicit opioids was associated with higher odds of naloxone access and competency, but lifetime opioid use and being close to a person who uses opioids were not. Finally, among those familiar with naloxone, a higher perception of community stigma toward people who use opioids generally was associated with lower odds of naloxone access and competency. Higher perception of community stigma toward people who use heroin, methamphetamines, and cocaine, however, was associated with higher odds of naloxone access.

Conclusions
Our findings highlight the continued need for education on naloxone with a specific focus on access and competency to further reduce opioid-related overdose deaths. Specific focus should be placed on promoting naloxone knowledge among people with a higher likelihood of needing to administer naloxone to reduce otherwise avoidable deaths. Further work is needed to understand differences in the relationship between substance-specific perceived stigma and its association with naloxone access.
Circular RNAs and cervical cancer: friends or foes? A landscape on circRNA-mediated regulation of key signaling pathways involved in the onset and progression of HPV-related cervical neoplasms
Authors: Heydarnia Emad , Dorostgou Zahra , Hedayati Neda , Mousavi Vahide , Yahyazadeh Sheida , Alimohammadi Mina , Gheibi Mobina , Heidari Parasta , Igder Somayeh , Mafi Alireza , Vakili Omid 
Published: February 2024

AbstractCervical cancer (CC) is a common gynecologic malignancy, accounting for a significant proportion of women death worldwide. Human papillomavirus (HPV) infection is one of the major etiological causes leading to CC onset; however, genetic, and epigenetic factors are also responsible for disease expansion. Circular RNAs (circRNAs), which are known as a particular subset of non-coding RNA (ncRNA) superfamily, with covalently closed loop structures, have been reported to be involved in the progression of diverse diseases, especially neoplasms. In this framework, abnormally expressed circRNAs are in strong correlation with CC pathogenesis through regulating substantial signaling pathways. Also, these RNA molecules can be considered as promising biomarkers and therapeutic targets for CC diagnosis/prognosis and treatment, respectively. Herein, we first review key molecular mechanisms, including Wnt/β-catenin, MAPK, and PI3K/Akt/mTOR signaling pathways, as well as angiogenesis and metastasis, by which circRNAs interfere with CC development. Then, diagnostic, prognostic, and therapeutic potentials of these ncRNA molecules will be highlighted in depth.
The perception of fungi among Karajá indigenous children and adolescents from Brazil
Authors: dos Reis Mazulkieliche Jeronimo , Leonardo-Silva Lucas , Xavier-Santos Solange 
Published: February 2024

Abstract
Background
Environmental perception involves the interpretation and interaction of individuals with their surroundings, influenced by cultural, social, and individual factors. Analyzing the environmental perception of children and adolescents contributes to fostering awareness and ethical behavior toward the environment. Indigenous communities, such as the Karajá from Brazil, possess significant environmental knowledge due to their connection with nature, providing distinctive insights into biodiversity and natural interconnections. In this study, the perception of fungi among Karajá indigenous children and adolescents was investigated.

Methods
The study involved 229 elementary school students from the Macaúba, Fontoura and Santa Isabel do Morro communities, located on Bananal Island, Brazil. Students were encouraged to draw what they knew about fungi and answer where they learned about fungi and what name they give to these organisms. The drawings were analyzed considering seven categories.

Results
The term most used to refer to fungi was hedoro(u) (56%), followed by fungus (21%) and mushroom (11%). Most students said they had learned about fungi in nature (38%) and at school (36%). The most represented organisms were in fact fungi (93%), mainly being portrayed in nature (94%). Most participants did not attribute any ecological function to fungi (83%), although 16% of them recognized fungi as decomposers and 1% as phytopathogenic agents. Negative aspects, particularly food contamination, were more frequently represented (13%) than positive aspects (4%). The drawings identified two morphological types: mushrooms (87%) and mold (13%). Among these mushrooms, 68% possibly represent the Amanita muscaria species.

Conclusions
Although the children and adolescents showed that they noticed the fungi around them, the group’s concept and understanding were limited to the figure of the mushroom and the negative aspects related to food contamination. Strong association of the fungi with the A. muscaria is noteworthy, since it does not occur in the environment in which the participants live, suggesting that external stimuli, such as TV or the internet, can influence their perception more than the nature they are exposed to.
Non-mitotic proliferation of malignant cancer cells revealed through live-cell imaging of primary and cell-line cultures
Authors: Tyagi Iram Shazia , Tsui Ho Yin Calvin , Chen Si , Li Xinyi , Mat Wai-Kin , Khan Muhammad A. , Choy Lucas Brendan , Chan Ka-Yin Aden , Chan Tat-Ming Danny , Ng Chi-Ping Stephanie , Ng Ho-Keung , Poon Wai Sang , Xue Hong 
Published: February 2024

Abstract
Introduction
Anti-mitosis has been a key strategy of anti-cancer therapies, targeting at a fundamental property of cancer cells, their non-controllable proliferation due to overactive mitotic divisions. For improved anti-cancer therapies, it is important to find out whether cancer cells can proliferate independent of mitosis and become resistant to anti-mitotic agents.

Results
In this study, live-cell imaging was applied to both primary-cultures of tumor cells, and immortalized cancer cell lines, to detect aberrant proliferations. Cells isolated from various malignant tumors, such as Grade-III hemangiopericytoma, atypical meningioma, and metastatic brain tumor exhibit distinct cellular behaviors, including amoeboid sequestration, tailing, tunneling, nucleic DNA leakage, as well as prokaryote-like division such as binary fission and budding-shedding, which are collectively referred to and reported as ‘non-mitotic proliferation’ in this study. In contrast, benign tumors including Grade-I hemangiopericytoma and meningioma were not obvious in such behaviors. Moreover, when cultured in medium free of any anti-cancer drugs, cells from a recurrent Grade-III hemangiopericytoma that had been subjected to pre-operation adjuvant chemotherapy gradually shifted from non-mitotic proliferation to abnormal mitosis in the form of daughter number variation (DNV) and endomitosis, and eventually regular mitosis. Similarly, when treated with the anti-cancer drugs Epirubicin or Cisplatin, the cancer cell lines HeLa and A549 showed a shift from regular mitosis to abnormal mitosis, and further to non-mitosis as the dominant mode of proliferation with increasing drug concentrations. Upon removal of the drugs, the cells reversed back to regular mitosis with only minor occurrences of abnormal mitosis, accompanied by increased expression of the stem cell markers ALDH1, Sox, Oct4 and Nanog.

Conclusions
The present study revealed that various types of malignant, but not benign, cancer cells exhibited cellular behaviors indicative of non-mitotic proliferation such as binary fission, which was typical of prokaryotic cell division, suggesting cell level atavism. Moreover, reversible transitions through the three modes of proliferation, i.e., mitosis, abnormal mitosis and non-mitosis, were observed when anticancer drug concentrations were grossly increased inducing non-mitosis or decreased favoring mitosis. Potential clinical significance of non-mitotic proliferation in cancer drug resistance and recurrence, and its relationship with cancer stem cells are worthy of further studies.
Determinants of survival following heart transplantation in adults with congenital heart disease
Authors: Sicim Hüseyin , Noly Pierre Emmanuel , Naik Suyash , Sood Vikram , Ohye Richard G. , Haft Jonathan W. , Aaronson Keith D. , Pagani Francis D. , Si Ming-Sing , Tang Paul C. 
Published: February 2024

Abstract
Background
Adult patients surviving with congenital heart disease (ACHD) is growing. We examine the factors associated with heart transplant outcomes in this challenging population with complex anatomy requiring redo-surgeries.

Methods
We reviewed the United Network for Organ Sharing-Standard Transplant Analysis and Research database and analyzed 35,952 heart transplants from January 1st, 2000, to September 30th, 2018. We compared transplant characteristics for ischemic cardiomyopathy (ICM) (n = 14,236), nonischemic cardiomyopathy (NICM) (n = 20,676), and ACHD (n = 1040). Mean follow-up was 6.20 ± 4.84 years. Kaplan–Meier survival curves and Cox-proportional hazards analysis were used to analyze survival data.

Results
Multivariable analysis confirmed that ACHD was associated greater in-hospital death compared to ICM (HR = 0.54, P < 0.001) and NICM (HR = 0.46, P < 0.001). Notable factors associated with increased mortality were history of cerebrovascular disease (HR = 1.11, P = 0.026), prior history of malignancy (HR = 1.12, P = 0.006), pre-transplant biventricular support (HR = 1.12, P = 0.069), postoperative stroke (HR = 1.47, P < 0.001) and postoperative dialysis (HR = 1.71, P < 0.001). ACHD transplants had a longer donor heart ischemic time (P < 0.001) and trend towards more deaths from primary graft dysfunction (P = 0.07). In-hospital deaths were more likely with ACHD and use of mechanical support such as use of right ventricular assist device (HR = 2.20, P = 0.049), biventricular support (HR = 1.62, P < 0.001) and extracorporeal membrane oxygenation (HR = 2.36, P < 0.001). Conditional survival after censoring hospital deaths was significantly higher in ACHD (P < 0.001).

Conclusion
Heart transplant in ACHD is associated with a higher post-operative mortality given anatomical complexity but a better long-term conditional survival. Normothermic donor heart perfusion may improve outcomes in the ACHD population by reducing the impact of longer ischemic times.