bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nilotinib vs dasatinib in achieving MR4.5 for de novo chronic myeloid leukemia: the randomized JALSG CML212 study
Authors: Matsumura Itaru , Ohtake Shigeki , Atsuta Yoshiko , Kurata Mio , Minami Yosuke , Takahashi Naoto , Nakaseko Chiaki , Iriyama Noriyoshi , Fujimaki Katsumichi , Kakihana Kazuhiko , Ogasawara Yoji , Ono Takaaki , Okada Masaya , Tauchi Tetsuzo , Miyamoto Toshihiro , Ohnishi Kazunori , Sakaida Emiko , Fujisawa Shin , Kobayashi Yukio , Asou Norio , Naoe Tomoki , Kiyoi Hitoshi , Miyazaki Yasushi 
Published: July 2024

Abstract
Deep molecular response (DMR) is a prerequite for treatment-free remission (TFR) in chronic myeloid leukemia in chronic phase (CML-CP). The JALSG (Japan Adult Leukemia Study Group) conducted a prospective randomized phase 3 CML212 study for de novo CML-CP to compare the cumulative achievement of molecular response 4.5 (MR4.5; international scale BCR::ABL1 ≤0.0032%) by 18 months between nilotinib and dasatinib treatment as a primary end point. A total of 454 patients were randomly assigned to the 300 mg nilotinib twice daily arm or to the 100 mg dasatinib daily arm (both n = 227). BCR::ABL1 messenger RNA levels were monitored every 3 months. Study treatment was stopped if the patients were judged as failure according to the European LekemiaNet 2009 criteria or showed intolerance. The cumulative achievement rates of MR4.5 by 18 months were 32.6% (95% confidence interval [CI], 26.5-39.1) in the nilotinib arm and 30.8% (95% CI, 24.9-37.3) in the dasatinib arm with no significant difference (P = .66). The cumulative achievement rates of early molecular response, complete cytogenetic response, and major molecular response by 12, 18, 24, and 36 months were almost the same between the 2 arms. There was no significant difference in progression-free survival (PFS) or overall survival (OS) between the 2 arms by log-rank tests (PFS, P = .58; OS, P = .64). These results suggest that nilotinib and dasatinib would be equally effective for patients with de novo CML-CP. This trial was registered in the University Hospital Medical Information Network Clinical Trials Registry as #UMIN000007909.
Proteome profiling of cutaneous leishmaniasis lesions due to dermotropic Leishmania donovani in Sri Lanka
Authors: Manamperi Nuwani H. , Edirisinghe Nimesha Madhushani , Wijesinghe Harshima , Pathiraja Lakmali , Pathirana Nishantha , Wanasinghe Vishmi Samudika , De Silva Chamalka Gimhani , Abeyewickreme W. , Karunaweera Nadira D. 
Published: July 2024

Abstract
Background
Characterization of the host response in cutaneous leishmaniasis (CL) through proteome profiling has gained limited insights into leishmaniasis research compared to that of the parasite. The primary objective of this study was to comprehensively analyze the proteomic profile of the skin lesions tissues in patients with CL, by mass spectrometry, and subsequent validation of these findings through immunohistochemical methods.

Methods
Eight lesion specimens from leishmaniasis-confirmed patients and eight control skin biopsies were processed for proteomic profiling by mass spectrometry. Formalin-fixed paraffin-embedded lesion specimens from thirty patients and six control skin specimens were used for Immunohistochemistry (IHC) staining. Statistical analyses were carried out using SPSS software. The chi-square test was used to assess the association between the degree of staining for each marker and the clinical and pathological features.

Results
Sixty-seven proteins exhibited significant differential expression between tissues of CL lesions and healthy controls (p < 0.01), representing numerous enriched biological processes within the lesion tissue, as evident by both the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases. Among these, the integrated endoplasmic reticulum stress response (IERSR) emerges as a pathway characterized by the up-regulated proteins in CL tissues compared to healthy skin. Expression of endoplasmic reticulum (ER) stress sensors, inositol-requiring enzyme-1 (IRE1), protein kinase RNA-like ER kinase (PERK) and activating transcription factor 6 (ATF6) in lesion tissue was validated by immunohistochemistry.

Conclusions
In conclusion, proteomic profiling of skin lesions carried out as a discovery phase study revealed a multitude of probable immunological and pathological mechanisms operating in patients with CL in Sri Lanka, which needs to be further elaborated using more in-depth and targeted investigations. Further research exploring the intricate interplay between ER stress and CL pathophysiology may offer promising avenues for the development of novel diagnostic tools and therapeutic strategies in combating this disease.
EAF2 Downregulation Recruits Tumor-associated Macrophages in Prostate Cancer through Upregulation of MIF
Authors: Cao Tianyu , Sun Qian , Shi Xiaoqin , Lin Xiuke , Lin Qingyuan , Zhu Jinchao , Xu Junhao , Cui Di , Shi Youwei , Jing Yifeng , Guo Wenhuan 
Published: July 2024

Abstract
Background
The role of tumor inflammatory microenvironment in the advancement of cancer, particularly prostate cancer, is widely acknowledged. ELL-associated factor 2 (EAF2), a tumor suppressor that has been identified in the prostate, is often downregulated in prostate cancer. Earlier investigations have shown that mice with EAF2 gene knockout exhibited a substantial infiltration of inflammatory cells into the prostatic stroma.

Methods
A cohort comprising 38 patients who had been diagnosed with prostate cancer and subsequently undergone radical prostatectomy (RP) was selected. These patients were pathologically graded according to the Gleason scoring system and divided into two groups. The purpose of this selection was to investigate the potential correlation between EAF2 and CD163 using immunohistochemistry (IHC) staining. Additionally, in vitro experimentation was conducted to verify the relationship between EAF2 expression, macrophage migration and polarization.

Results
Our study demonstrated that in specimens of human prostate cancer, the expression of EAF2 was notably downregulated, and this decrease was inversely associated with the number of CD163-positive macrophages that infiltrated the cancerous tissue. Cell co-culture experiments revealed that the chemotactic effect of tumor cells towards macrophages was intensified and that macrophages differentiated into tumor-associated macrophages (TAMs) when EAF2 was knocked out. Additionally, the application of cytokine protein microarray showed that the expression of chemokine macrophage migration inhibitory factor (MIF) increased after EAF2 knockout.

Conclusions
Our findings suggested that EAF2 was involved in the infiltration of CD163-positive macrophages in prostate cancer via MIF.

Graphical abstract
Population genetic structure of Culex tritaeniorhynchus in different types of climatic zones in China
Authors: Zhang Ye , Wang Haifang , Du Jun , Wang Yandong , Zang Chuanhui , Cheng Peng , Liu Lijuan , Zhang Chongxing , Lou Ziwei , Lei Jingjing , Wu Jiahui , Gong Maoqing , Liu Hongmei 
Published: July 2024

Abstract
Background
Culex tritaeniorhynchus is widely distributed in China, from Hainan Island in the south to Heilongjiang in the north, covering tropical, subtropical, and temperate climate zones. Culex tritaeniorhynchus carries 19 types of arboviruses. It is the main vector of the Japanese encephalitis virus (JEV), posing a serious threat to human health. Understanding the effects of environmental factors on Culex tritaeniorhynchus can provide important insights into its population structure or isolation patterns, which is currently unclear.

Results
In total, 138 COI haplotypes were detected in the 552 amplified sequences, and the haplotype diversity (Hd) value increased from temperate (0.534) to tropical (0.979) regions. The haplotype phylogeny analysis revealed that the haplotypes were divided into two high-support evolutionary branches. Temperate populations were predominantly distributed in evolutionary branch II, showing some genetic isolation from tropical/subtropical populations and less gene flow between groups. The neutral test results of HNQH (Qionghai) and HNHK(Haikou) populations were negative (P < 0.05), indicating many low-frequency mutations in the populations and that the populations might be in the process of expansion. Moreover, Wolbachia infection was detected only in SDJN (Jining) (2.24%), and all Wolbachia genotypes belonged to supergroup B. To understand the influence of environmental factors on mosquito-borne viruses, we examined the prevalence of Culex tritaeniorhynchus infection in three ecological environments in Shandong Province. We discovered that the incidence of JEV infection was notably greater in Culex tritaeniorhynchus from lotus ponds compared to those from irrigation canal regions. In this study, the overall JEV infection rate was 15.27 per 1000, suggesting the current risk of Japanese encephalitis outbreaks in Shandong Province.

Conclusions
Tropical and subtropical populations of Culex tritaeniorhynchus showed higher genetic diversity and those climatic conditions provide great advantages for the establishment and expansion of Culex tritaeniorhynchus. There are differences in JEV infection rates in wild populations of Culex tritaeniorhynchus under different ecological conditions. Our results suggest a complex interplay of genetic differentiation, population structure, and environmental factors in shaping the dynamics of Culex tritaeniorhynchus. The low prevalence of Wolbachia in wild populations may reflect the recent presence of Wolbachia invasion in Culex tritaeniorhynchus.
Impact of neighborhood context on self-rated health among very old adults living in Germany: a cross-sectional representative study
Authors: Zimmermann Jaroslava 
Published: July 2024

Abstract
Background
Increasingly, evidence has shown that different aspects of neighborhood context play a significant role in self-rated health, one of the key health indicators in advanced age. Nevertheless, very old adults are often under represented or excluded from such research. Therefore, the first aim of this study was to examine whether social, socioeconomic, and physical neighborhood context is associated with self-rated health in the very old population of Germany. The second objective was to explore whether the link of socioeconomic and physical neighborhood context with self-rated health is moderated by availability of social resources in neighborhoods.

Methods
Data from the representative survey, “Old Age in Germany” (D80+) were employed. In total, the study sample of D80+ included 10,578 individuals aged 80 years and over. Additionally, the D80+ data were matched with the freely accessible regional dataset of the Federal Institute for Research on Building, Urban Affairs, and Spatial Development. Two self-rated items (place attachment and social cohesion) were used to assess social neighborhood context. Socioeconomic context of neighborhoods was operationalized by German index of socioeconomic deprivation. To evaluate physical context, perceived measures of building conditions and walkability were included. Using the maximum likelihood estimator with robust standard errors, logistic regression models were estimated to analyze the relationship between neighborhood context (social, socioeconomic, and physical context, as well as their interactions) and self-rated health.

Results
Including 8,066 participants in the analysis, the findings showed that better condition of residential building, higher walkability, being closely attached to outdoor places, and higher social cohesion were associated with higher chance to report good self-rated health of very old adults. In the adjusted models, the German socioeconomic deprivation index was not related to self-rated health. The effect of socioeconomic and physical neighborhood context on self-rated health did not differ according available neighborhood social resources.

Conclusions
The results indicate that especially more favorable conditions in social and physical neighborhood context are associated with good self-rated health in the very old population of Germany. Further studies should consider multiple aspects of neighborhood context as well as their interplay when examining the neighborhood impact on self-rated health in older populations.
Clinical efficacy and safety of transvaginal natural orifice transluminal endoscopic surgery for benign adnexal disease: a prospective trial
Authors: Yan Jinbowen , Zhou Dan , Zhang Shuo , Zhang Bo , Tuo Xunyuan , Meng Qingwei , Lv Qiubo 
Published: July 2024

Abstract
Background
There is a scarcity of prospective clinical research evidence regarding the utilization of transvaginal natural orifice translumenal endoscopic surgery (vNOTES) as a treatment option for ovarian cysts. The objective of this study was to assess the feasibility and safety of employing vNOTES for the management of ovarian cysts.

Methods
Our study included women between the ages of 18 and 70 who intended to undergo surgical intervention for benign lesions. Stratified blocked randomization was employed to allocate participants into groups. The main objective was to assess whether the assigned group adhered to the recommended surgical technique for ovarian cystectomy or adnexectomy, without any deviation to alternative surgical methods.

Results
A total of 196 patients were included in the study, with all surgeries in each group being conducted according to the assigned procedures. Among them, the ovarian cystectomy layer included 58 cases in the vNOTES group and 58 cases in the conventional laparoscopy (CL) groups. The adnexectomy layer included 40 cases in the vNOTES group and 40 cases in the CL group. Utilizing a sensitivity analysis, the two-sided 95% lower confidence limit was determined to be 5.5% for the disparity in proportions between the vNOTES groups and CL groups. These lower limits fell below the predetermined non-inferiority margin of 10%.

Conclusions
The study findings demonstrate that vNOTES was not inferior to CL in terms of adnexectomy or ovarian cystectomy. vNOTES can be considered a more minimally invasive surgical approach, as it results in reduced postoperative pain, faster recovery, and absence of visible incisions. Overall, vNOTES proves to be a safe, feasible, and less invasive treatment option.

Trial registration
This study retrospectively registered with the China Clinical Trial Registry with the registration number ChiCTR2100052223(22-10-2021).
Psychometric properties of the Arabic version of PHEEM applied on a sample of medical residents in Syria
Authors: Alfakhry Ghaith , Kodmani Rama , Almasri Imad Addin 
Published: July 2024

Abstract
Background
The clinical learning environment (CLE) plays a crucial role in shaping the learning experiences and professional development of medical professionals. Understanding and optimising this environment is essential for improving doctors’ knowledge acquisition, clinical skills, and overall well-being. The development of the Postgraduate Hospital Educational Environment Measure (PHEEM) and its translation to numerous languages has been a milestone in clinical education. Even though PHEEM was recently translated into Arabic, its psychometric properties in this form remain unevaluated. Therefore, this study aims to conduct a comprehensive psychometric analysis of the Arabic version of the PHEEM questionnaire.

Methods
This is a cross-sectional questionnaire survey validation study. The defined population were medical residents in Damascus, Syria. A paper-based survey as well as an online-based one were conducted using several non-probability sampling methods namely, convenience, river and, snowball sampling between June 15, 2023, and June 21, 2023. Both exploratory (EFA) and confirmatory (CFA) factor analyses were conducted. Several psychometric criteria were applied including scree plot, eigenvalue > 1.5 and the ‘proportion of variance accounted for’ criterion.

Results
A total of 543 participants completed the questionnaire (56.9% female). Kaiser-Meyer-Olkin measure for sample adequacy was high (0.937) and the P-value for Bartlett’s test was < 0.001. EFA revealed five meaningful factors which were labelled: perception of teachers, learner’s engagement and social participation, external regulation, work culture, and living conditions. These factors had the following eigenvalues: 12.6, 2.18, 2.03, 1.86, and 1.41 respectively, with a total explained variance of 43.45%. Cronbach’s Alpha was 0.938. CFA confirmed the model structure of EFA (SRMR = 0.067 and RMSEA = 0.066). The Average Variance Explained (AVE) value of any given factor was > 0.7.

Discussion
The Arabic PHEEM inventory demonstrated satisfactory psychometric properties. The extracted domains are of theoretical relevance to the psychosocial-material conceptual framework for learning environment. Nonetheless, this validation was performed in the Syrian context; therefore, future studies in other Arabic countries are recommended to support the applicability of Arabic PHEEM in the wide Arab World.
Genetic evidence for causal association between migraine and dementia: a mendelian randomization study
Authors: Chen Qiuyi , Zhang Chengcheng , Wu Shiyang , He Yiwei , Liu Yuhan , Zheng Libin , Li Bin , Liu Guiyou , Liu Lu 
Published: July 2024

Abstract
Background
There is an association between migraine and dementia, however, their causal relationship remains unclear. This study employed bidirectional two-sample Mendelian randomization (MR) to investigate the potential causal relationship between migraine and dementia and its subtypes: Alzheimer’s disease (AD), vascular dementia (VaD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB).

Methods
Summary-level statistics data were obtained from publicly available genome-wide association studies (GWAS) for both migraine and five types of dementia. Single nucleotide polymorphisms (SNPs) associated with migraine and each dementia subtype were selected. MR analysis was conducted using inverse variance weighting (IVW) and weighted median (WM) methods. Sensitivity analyses included Cochran’s Q test, MR pleiotropy residual sum and outlier (MR-PRESSO) analysis, the intercept of MR-Egger, and leave-one-out analysis.

Results
Migraine showed a significant causal relationship with AD and VaD, whereas no causal relationship was observed with all-cause dementia, FTD, or DLB. Migraine may be a potential risk factor for AD (odds ratio [OR]: 1.09; 95% confidence interval [CI]: 0.02–0.14; P = 0.007), while VaD may be a potential risk factor for migraine (OR: 1.04; 95% CI: 0.02–0.06; P = 7.760E-5). Sensitivity analyses demonstrated the robustness of our findings.

Conclusion
Our study suggest that migraine may have potential causal relationships with AD and VaD. Migraine may be a risk factor for AD, and VaD may be a risk factor for migraine. Our study contributes to unraveling the comprehensive genetic associations between migraine and various types of dementia, and our findings will enhance the academic understanding of the comorbidity between migraine and dementia.
The role of lncRNA NEAT1 in human cancer chemoresistance
Authors: Long Feng , Li Xue , Pan Jingyu , Ye Hailin , Di Cuixia , Huang Yong , Li Jiawei , Zhou Xuan , Yi Huiyi , Huang Qiaozhen , Si Jing 
Published: July 2024

AbstractChemotherapy is currently one of the most effective methods in clinical cancer treatment. However, chemotherapy resistance is an important reason for poor chemotherapy efficacy and prognosis, which has become an urgent problem to be solved in the field of cancer chemotherapy. Therefore, it is very important to deeply study and analyze the mechanism of cancer chemotherapy resistance and its regulatory factors. Long non-coding RNA nuclear paraspeckle assembly transcript 1 (LncRNA NEAT1) has been shown to be closely associated with chemotherapy resistance in cancer. NEAT1 induces cancer cell resistance to chemotherapeutic drugs by regulating cell apoptosis, cell cycle, drug transport and metabolism, DNA damage repair, EMT, autophagy, cancer stem cell characteristics, and metabolic reprogramming. This indicates that NEAT1 may be an important target to overcome chemotherapy resistance and is expected to be a potential biomarker to predict the effect of chemotherapy. This article summarizes the expression characteristics and clinical characteristics of NEAT1 in different cancers, and deeply discusses the regulatory role of NEAT1 in cancer chemotherapy resistance and related molecular mechanisms, aiming to clarify NEAT1 as a new target to overcome cancer chemotherapy resistance and the feasibility of chemotherapy sensitizers, with a view to providing a potential therapeutic direction for overcoming the dilemma of cancer resistance in the future.
Exposure to heavy metals in utero and autism spectrum disorder at age 3: a meta-analysis of two longitudinal cohorts of siblings of children with autism
Authors: Dou John F. , Schmidt Rebecca J. , Volk Heather E. , Nitta Manon M. , Feinberg Jason I. , Newschaffer Craig J. , Croen Lisa A. , Hertz-Picciotto Irva , Fallin M. Daniele , Bakulski Kelly M. 
Published: July 2024

Abstract
Background
Autism spectrum disorder (ASD) is a prevalent and heterogeneous neurodevelopmental disorder. Risk is attributed to genetic and prenatal environmental factors, though the environmental agents are incompletely characterized.

Methods
In Early Autism Risk Longitudinal Investigation (EARLI) and Markers of Autism Risk in Babies Learning Early Signs (MARBLES), two pregnancy cohorts of siblings of children with ASD, urinary metals concentrations during two pregnancy time periods (< 28 weeks and ≥ 28 weeks of gestation) were measured using inductively coupled plasma mass spectrometry. At age three, clinicians assessed ASD with DSM-5 criteria. In an exposure-wide association framework, using multivariable log binomial regression, we examined each metal for association with ASD status, adjusting for gestational age at urine sampling, child sex, age at pregnancy, race/ethnicity and education. We meta-analyzed across the two cohorts.

Results
In EARLI (n = 170) 17% of children were diagnosed with ASD, and 44% were classified as having non-neurotypical development (Non-TD). In MARBLES (n = 231), 21% were diagnosed with ASD, and 14% classified as Non-TD. During the first and second trimester period (< 28 weeks), having cadmium concentration over the level of detection was associated with 1.69 (1.08, 2.64) times higher risk of ASD, and 1.29 (0.95, 1.75)times higher risk of Non-TD.
A doubling of first and second trimester cesium concentration was marginally associated with 1.89 (0.94, 3.80) times higher risk of ASD, and a doubling of third trimester cesium with 1.69 (0.97, 2.95) times higher risk of ASD.

Conclusion
Exposure in utero to elevated levels of cadmium and cesium, as measured in urine collected during pregnancy, was associated with increased risk of developing ASD.