bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes of hematopoietic stem cell transplantation in 813 pediatric patients with Fanconi anemia
Authors: Lum Su Han , Eikema Dirk-Jan , Piepenbroek Brian , Wynn Robert F. , Samarasinghe Sujith , Dalissier Arnaud , Kalwak Krysztof , Ayas Mouhab , Hamladji Rose-Marie , Yesilipek Akif , Dalle Jean-Hugues , Uckan-Cetinkaya Duygu , Bierings Marc , Kupesiz Alphan , Halahleh Khalid , Skorobogatova Elena , Öztürk Gülyüz , Faraci Maura , Renard Cecile , Evans Pamela , Corbacioglu Selim , Locatelli Franco , Dufour Carlo , Risitano Antonio , Peffault de Latour Régis
Published: July 2024

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only established curative option for Fanconi anemia (FA)–associated bone marrow failure (BMF)/aplastic anemia (AA) and acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS). We performed a retrospective multicenter study on 813 children with FA undergoing first HSCT between 2010 and 2018. Median duration of follow-up was 3.7 years. Median age at transplant was 8.8 years (IQR, 6.5-18.1). Five-year overall survival (OS), event-free survival (EFS), and graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) were 83% (95% confidence interval [CI], 80-86), 78% (95% CI, 75-81), and 70% (95% CI, 67-74), respectively. OS was comparable between matched family donor (MFD; n = 441, 88%) and matched unrelated donor (MUD; n = 162, 86%) and was superior to that of mismatched family donor (MMFD) or mismatched unrelated donor (MMUD; n = 144, 72%) and haploidentical donor (HID; n = 66, 70%; P < .001). In multivariable analysis, a transplant indication of AML/MDS (vs AA/BMF), use of MMFD/MMUD and HID (vs MFD), and fludarabine-cyclophosphamide (FluCy) plus other conditioning (vs FluCy) independently predicted inferior OS, whereas alemtuzumab vs antithymocyte globulin was associated with better OS. Age ≥10 years was associated with worse EFS and GRFS. Cumulative incidences (CINs) of primary and secondary graft failure were 2% and 3% respectively. CINs of grade 3 to 4 acute GVHD and chronic GVHD were 12% and 8% respectively. The 5-year CIN of secondary malignancy was 2%. These data suggest that HSCT should be offered to patients with FA with AA/BMF at a younger age in the presence of a well-matched donor.
Homoharringtonine inhibits the NOTCH/MYC pathway and exhibits antitumor effects in T-cell acute lymphoblastic leukemia
Authors: Suo Shanshan , Zhao Dandan , Li Fenglin , Zhang Yi , Rodriguez-Rodriguez Sonia , Nguyen Le Xuan Truong , Ghoda Lucy , Carlesso Nadia , Marcucci Guido , Zhang Bin , Jin Jie
Published: July 2024

We report on the antileukemic activity of homoharringtonine (HHT) in T-cell acute lymphoblastic leukemia (T-ALL). We showed that HHT inhibited the NOTCH/MYC pathway and induced significantly longer survival in mouse and patient-derived T-ALL xenograft models, supporting HHT as a promising agent for T-ALL.
Multiomics analysis of IgM monoclonal gammopathies reveals epigenetic influence on oncogenesis via DNA methylation
Authors: Chohan Karan , Paludo Jonas , Dasari Surendra , Mondello Patrizia , Novak Joseph P. , Abeykoon Jithma P. , Wenzl Kerstin , Yang Zhi-Zhang , Jalali Shahrzad , Bhardwaj Vaishali , Krull Jordan E. , Braggio Esteban , Manske Michelle K. , Paulus Aneel , Reeder Craig B. , Ailawadhi Sikander , Chanan-Khan Asher , Kapoor Prashant , Kyle Robert A. , Gertz Morie A. , Novak Anne J. , Ansell Stephen M.
Published: July 2024

Currently, the role of DNA methylation in the immunoglobulin M (IgM) monoclonal gammopathy disease spectrum remains poorly understood. In the present study, a multiomics prospective analysis was conducted integrating DNA methylation, RNA sequencing (RNA-seq), and whole-exome sequencing data in 34 subjects (23 with Waldenström macroglobulinemia [WM], 6 with IgM monoclonal gammopathy of undetermined significance [MGUS], and 5 normal controls). Analysis was focused on defining differences between IgM gammopathies (WM/IgM-MGUS) compared with controls, and specifically between WM and IgM-MGUS. Between groups, genome-wide DNA methylation analysis demonstrated a significant number of differentially methylated regions that were annotated according to genomic region. Next, integration of RNA-seq data was performed to identify potentially epigenetically deregulated pathways. We found that pathways involved in cell cycle, metabolism, cytokine/immune signaling, cytoskeleton, tumor microenvironment, and intracellular signaling were differentially activated and potentially epigenetically regulated. Importantly, there was a positive enrichment of the CXCR4 signaling pathway along with several interleukin (interleukin 6 [IL-6], IL-8, and IL-15) signaling pathways in WM compared with IgM-MGUS. Further assessment of known tumor suppressor genes and oncogenes uncovered differential promoter methylation of several targets with concordant change in gene expression, including CCND1 and CD79B. Overall, this report defines how aberrant DNA methylation in IgM gammopathies may play a critical role in the epigenetic control of oncogenesis and key cellular functions.
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

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

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

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

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

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

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

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

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

Chemotherapy 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

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.
Effects of magnesium supplementation on muscle soreness in different type of physical activities: a systematic review
Authors: Tarsitano Maria Grazia , Quinzi Federico , Folino Katia , Greco Francesca , Oranges Francesco Pio , Cerulli Claudia , Emerenziani Gian Pietro
Published: July 2024

Background

Magnesium is a micronutrient and an intracellular cation responsible for different biochemical reactions involved in energy production and storage, control of neuronal and vasomotor activity, cardiac excitability, and muscle contraction. Magnesium deficiency may result in impaired physical performance. Moreover, magnesium plays an important role on delayed onset muscle soreness after training. Thus, physically active individuals and sport specialists have to pay attention to magnesium supplementation (MgS). However, the type, timing and dosage of magnesium intake are not well elucidated yet. Hence, we aimed to systematically review the literature regarding the effects of MgS on muscle soreness in physically active individuals. We focused exclusively on MgS, excluding those studies in which magnesium was administered together with other substances.

Methods

Three electronic databases and literature sources (PUBMED, SCOPUS and Web of Sciences-Core Collection) were searched, in accordance with PRISMA guidelines. After the database search, 1254 articles were identified, and after excluding duplicates, 960 articles remained. Among these, 955 were excluded following the title and abstract screening. The remaining 5 articles were screened in full text and 4 study met the eligibility criteria.

Results

These studies showed that MgS reduced muscle soreness, improved performance, recovery and induced a protective effect on muscle damage.

Conclusion

To reach these positive effects, individuals engaged in intense exercise should have a Mg requirement 10–20% higher than sedentary people, to be taken in capsules and 2 h before training. Moreover, it is suggested to maintain magnesium levels in the recommended range during the off-season.

Systematic review registration

PROSPERO registration number: CRD42024501822.
Molecular alterations and prognosis of breast cancer with cutaneous metastasis
Authors: Xu Yan , Ding Li , Li Chao , Hua Bin , Wang Sha , Zhang Junli , Liu Cuicui , Guo Rongyun , Zhang YongQiang
Published: July 2024

Purpose

Cutaneous metastasis (CM) accounts for 5–30% of patients with breast cancer (BC) and presents unfavorable response to treatment and poor prognosis. A better understanding of the molecular alterations involved in metastasis is essential, which would help identify diagnostic and efficacy biomarkers for CM.

Materials

: We retrospectively reviewed a total of 13 patients with histological or cytological diagnosis of breast cancer and CM. Clinical information was extracted from the medical records. The mutational landscape of matched primary tumors with their lymph nodes or CM tissues were analyzed using next-generation sequencing (NGS) of 425 cancer-relevant genes. All tissues were also analyzed by immunohistochemistry (IHC). The association of prognosis with various clinical and molecular factors was also evaluated.

Results

More than half of the patients were Ki67 low (< 50%, 53.7%). Most patients (12, 92.3%) had other metastasis sites other than skin. The median time from diagnosis to the presentation of CM (T1) was 15 months (range: 0–94 months) and the median time from CM to death (T2) was 13 months (range 1–78). The most frequently altered genes across the three types of tissues were TP53 (69.6%, 16/23), PIK3CA (34.8%, 8/23), and MYC (26.1%). The number of alterations in CM tends to be higher than in primary tumors (median 8 vs. 6, P = 0.077). Copy number loss in STK11, copy number gain in FGFR4, TERT, AR, FLT4 and VEGFA and mutations in ATRX, SRC, AMER1 and RAD51C were significantly enriched in CM (all P < 0.05). Ki67 high group (> 50%) showed significantly shorter T1 than the Ki67 low group (≤ 50%) (median 12.5 vs. 50.0 months, P = 0.036). TP53, PIK3CA mutations, and TERT amplification group were associated with inferior T2 (median 11 vs. 36 months, P = 0.065; 8 vs. 36 months, P = 0.013, 7 vs. 36 months, P = 0.003, respectively). All p values were not adjusted.

Conclusion

We compared the genomic features of primary breast cancer tissues with their corresponding CM tissues and discussed potential genes and pathways that may contribute to the skin metastasis of advanced breast cancers patients. TP53, PIK3CA mutant, and TERT amplification may serve as biomarkers for poor prognosis for CM patients.
Conventional vs. endoscopic-assisted curettage of benign bone tumours. An experimental study
Authors: Smolle Maria Anna , Jud Lukas , Scheurer Fabrice André , Hoch Armando , Ackermann Jakob , Fritz Benjamin , Müller Daniel Andreas
Published: July 2024

Background

This experimental study aimed at directly comparing conventional and endoscopic-assisted curettage towards (1) amount of residual tumour tissue (RTT) and (2) differences between techniques regarding surgical time and surgeons’ experience level.

Methods

Three orthopaedic surgeons (trainee, consultant, senior consultant) performed both conventional (4x each) and endoscopic-assisted curettages (4x each) on specifically prepared cortical-soft cancellous femur and tibia sawbone models. “Tumours” consisted of radio-opaque polyurethane-based foam injected into prepared holes. Pre- and postinterventional CT-scans were carried out and RTT assessed on CT-scans. For statistical analyses, percentage of RTT in relation to total lesion’s volume was used. T-tests, Wilcoxon rank-sum tests, and Kruskal-Wallis tests were applied to assess differences between surgeons and surgical techniques regarding RTT and timing.

Results

Median overall RTT was 1% (IQR 1 – 4%). Endoscopic-assisted curettage was associated with lower amount of RTT (median, 1%, IQR 0 − 5%) compared to conventional curettage (median, 4%, IQR 0 − 15%, p = 0.024). Mean surgical time was prolonged with endoscopic-assisted (9.2 ± 2.9 min) versus conventional curettage (5.9 ± 2.0 min; p = 0.004). No significant difference in RTT amount (p = 0.571) or curetting time (p = 0.251) depending on surgeons’ experience level was found.

Conclusions

Endoscopic-assisted curettage appears superior to conventional curettage regarding complete tissue removal, yet at expenses of prolonged curetting time. In clinical practice, this procedure may be reserved for cases at high risk of recurrence (e.g. anatomy, histology).
Ovarian fibrosis: molecular mechanisms and potential therapeutic targets
Authors: Gu Mengqing , Wang Yibo , Yu Yang
Published: July 2024

Ovarian fibrosis, characterized by the excessive proliferation of ovarian fibroblasts and the accumulation of extracellular matrix (ECM), serves as one of the primary causes of ovarian dysfunction. Despite the critical role of ovarian fibrosis in maintaining the normal physiological function of the mammalian ovaries, research on this condition has been greatly underestimated, which leads to a lack of clinical treatment options for ovarian dysfunction caused by fibrosis. This review synthesizes recent research on the molecular mechanisms of ovarian fibrosis, encompassing TGF-β, extracellular matrix, inflammation, and other profibrotic factors contributing to abnormal ovarian fibrosis. Additionally, we summarize current treatment approaches for ovarian dysfunction targeting ovarian fibrosis, including antifibrotic drugs, stem cell transplantation, and exosomal therapies. The purpose of this review is to summarize the research progress on ovarian fibrosis and to propose potential therapeutic strategies targeting ovarian fibrosis for the treatment of ovarian dysfunction.
An open-label, randomized, non-inferiority trial of the efficacy and safety of ciprofloxacin versus an aminoglycoside + ciprofloxacin in the treatment of bubonic plague (IMASOY): study protocol for a randomized control trial—an update to the published protocol
Authors: Randremanana Rindra Vatosoa , Raberahona Mihaja , de Dieu Randria Mamy Jean , Bourner Josephine , Zadonirina Gabriella , Razananaivo Hanitra , Mayouya-Gamana Théodora , Mangahasimbola Reziky , Pesonel Elise , Gillesen Annelies , Rajerison Minoarisoa , Andrianaivoarimanana Voahangy , Edwards Tansy , Horby Peter , Olliaro Piero
Published: July 2024

This article reports an update to the protocol of the IMASOY trial, which was prospectively registered on clinicaltrials.gov (NCT04110340) in October 2019.
At what risk? A research note on interviewer burden
Authors: Melvin Khadijah , Sweeney Erin , Buchman Katherine , Winford Eboni , Ansah Jessica , Wairimu Sandra , Martinez Will , Laughter Judson , Tree Jennifer Jabson
Published: July 2024

Background

We report on our methodological experiences during an investigation of how institutional racism functions in healthcare. We found tension between balancing methodological rigor with the unanticipated consequence of interviewer burden.

Methods

Semi-structured interviews were conducted with patients. Interviews were recorded, transcribed verbatim, and qualitatively analyzed using thematic content analysis. Interviewers also participated in weekly debriefing sessions and reported experiences with patients.

Results

Interviewers repeatedly experienced negative encounters with white patients during interviews. Themes included privilege to avoid racism, denial of racism, non-verbal discomfort, falsely claiming Native identities, and intimidation. These experiences were most pronounced with Black interviewers.

Discussion

Interviewer burden may need to be a consideration taken up in a variety of research contexts.
The effect of transcranial alternating current stimulation on cognitive flexibility and attention of children with intellectual disability: a case report
Authors: Ghahri Lalaklou Zahra , Haghighat-Manesh Elahe , Montazeri Ghahjavarestani AmirHossein , Ahmadi Ezzatollah
Published: July 2024

Background

Intellectual disability is a neurodevelopmental disorder characterized by significant impairments in intellectual functioning and adaptive behavior. Cognitive flexibility and attention are crucial cognitive domains often affected in children with intellectual disability. This case report explores the novel use of transcranial alternating current stimulation, a noninvasive brain stimulation technique, to enhance these cognitive functions. The study’s novelty lies in its focus on alpha-wave frequency transcranial alternating current stimulation targeting specific Brodmann areas and its potential sustained impact on cognitive flexibility and attention in the pediatric population with intellectual disability.

Case presentation

The case study involved two elementary school students, both 7 years old with mild intellectual disability, one male and one female, both with Turkic ethnicity, from Shahid Fahmideh School for Exceptional Children in Khosrowshah, Iran. Both participants underwent a 2-week intervention with daily 20-minute sessions of transcranial alternating current stimulation at an alpha-wave frequency (10 Hz), targeting Brodmann areas F3 and P3. Cognitive flexibility and attention were assessed using the Wisconsin Card Sorting Test and the Clock Test, administered at four time points: pre-intervention, week 1, week 2, and 1 month post-intervention. Statistical analysis showed significant improvements in both Wisconsin Card Sorting Test and Clock Test scores for both participants compared with baseline, with sustained enhancement over time.

Conclusion

The findings from this case report indicate that transcranial alternating current stimulation may be a promising intervention for improving cognitive flexibility and attention in children with intellectual disability. The significant and sustained improvements observed suggest that transcranial alternating current stimulation could have a meaningful clinical impact on the cognitive development of this population. However, further research is needed to confirm the efficacy of transcranial alternating current stimulation and to explore its broader applicability and long-term effects in larger, more diverse populations.
Optimal control of a dengue model with cross-immunity
Authors: Kugelmann Bernd , Pulch Roland
Published: July 2024

Mathematical modelling of a dengue epidemic with two serotypes including a temporary cross-immunity yields a nonlinear system consisting of ordinary differential equations (ODEs). We investigate an optimal control problem, where the integral of the infected humans is minimised within a time interval. The controls represent human actions to decrease the number of mosquitos in the model. An integral constraint is added, which takes a limitation on the sum of the human actions into account. On the one hand, we derive and apply a direct approach to solve the optimal control problem. Therein, a discretisation of the controls is constructed using spline interpolation in time. Consequently, a finite-dimensional constrained minimisation problem can be solved. On the other hand, we employ an indirect approach, where necessary conditions for an optimal solution are considered. This technique yields a multipoint boundary value problem of a larger system of ODEs including adjoint equations. We present results of numerical computations, where the two methods are compared.
Salmonella enteritidis acquires phage resistance through a point mutation in rfbD but loses some of its environmental adaptability
Authors: Zeng Yukun , Li Ping , Liu Shenglong , Shen Mangmang , Liu Yuqing , Zhou Xin
Published: July 2024

Phage therapy holds promise as an alternative to antibiotics for combating multidrug-resistant bacteria. However, host bacteria can quickly produce progeny that are resistant to phage infection. In this study, we investigated the mechanisms of bacterial resistance to phage infection. We found that Rsm1, a mutant strain of Salmonella enteritidis (S. enteritidis) sm140, exhibited resistance to phage Psm140, which was originally capable of lysing its host at sm140. Whole genome sequencing analysis revealed a single nucleotide mutation at position 520 (C → T) in the rfbD gene of Rsm1, resulting in broken lipopolysaccharides (LPS), which is caused by the replacement of CAG coding glutamine with a stop codon TAG. The knockout of rfbD in the sm140ΔrfbD strain caused a subsequent loss of sensitivity toward phages. Furthermore, the reintroduction of rfbD in Rsm1 restored phage sensitivity. Moreover, polymerase chain reaction (PCR) amplification of rfbD in 25 resistant strains revealed a high percentage mutation rate of 64% within the rfbD locus. We assessed the fitness of four bacteria strains and found that the acquisition of phage resistance resulted in slower bacterial growth, faster sedimentation velocity, and increased environmental sensitivity (pH, temperature, and antibiotic sensitivity). In short, bacteria mutants lose some of their abilities while gaining resistance to phage infection, which may be a general survival strategy of bacteria against phages. This study is the first to report phage resistance caused by rfbD mutation, providing a new perspective for the research on phage therapy and drug-resistant mechanisms.
On the study of three-dimensional compressible Navier–Stokes equations
Authors: Abdelwahed Mohamed , Bade Rabe , Chaker Hedia , Hassine Maatoug
Published: July 2024

This work is devoted to the study of three-dimensional compressible Navier–Stokes equations on unstructured meshes. The approach used is based on separating the convection and diffusion parts. The convective flux is computed using the Godunov method. For the diffusive part, we present a new finite volume scheme. Numerical results are provided to demonstrate the efficiency of the developed technique.
Trending on the use of Google mobility data in COVID-19 mathematical models
Authors: Deng Yang , Lin Hefei , He Daihai , Zhao Yi
Published: July 2024

Google mobility data has been widely used in COVID-19 mathematical modeling to understand disease transmission dynamics. This review examines the extensive literature on the use of Google mobility data in COVID-19 mathematical modeling. We mainly focus on over a dozen influential studies using Google mobility data in COVID-19 mathematical modeling, including compartmental and metapopulation models. Google mobility data provides valuable insights into mobility changes and interventions. However, challenges persist in fully elucidating transmission dynamics over time, modeling longer time series and accounting for individual-level correlations in mobility patterns, urging the incorporation of diverse datasets for modeling in the post-COVID-19 landscape.
M2-type tumor-associated macrophages upregulated PD-L1 expression in cervical cancer via the PI3K/AKT pathway
Authors: Guo Fan , Kong Weina , Li Dewei , Zhao Gang , Anwar Miyessar , Xia Feifei , Zhang Yuanming , Ma Cailing , Ma Xiumin
Published: July 2024

Background and purpose

PD-1/PD-L1 inhibitors have become a promising therapy. However, the response rate is lower than 30% in patients with cervical cancer (CC), which is related to immunosuppressive components in tumor microenvironment (TME). Tumor-associated macrophages (TAMs), as one of the most important immune cells, are involved in the formation of tumor suppressive microenvironment. Therefore, it will provide a theoretical basis for curative effect improvement about the regulatory mechanism of TAMs on PD-L1 expression.

Methods

The clinical data and pathological tissues of CC patients were collected, and the expressions of PD-L1, CD68 and CD163 were detected by immunohistochemistry. Bioinformatics was used to analyze the macrophage subtypes involved in PD-L1 regulation. A co-culture model was established to observe the effects of TAMs on the morphology, migration and invasion function of CC cells, and the regulatory mechanism of TAMs on PD-L1.

Results

PD-L1 expression on tumor cells could predict the poor prognosis of patients. And there was a strong correlation between PD-L1 expression with CD163+TAMs infiltration. Similarly, PD-L1 expression was associated with M1/M2-type TAMs infiltration in bioinformatics analysis. The results of cell co-culture showed that M1/M2-type TAMs could upregulate PD-L1 expression, especially M2-type TAMs may elevate the PD-L1 expression via PI3K/AKT pathway. Meanwhile, M1/M2-type TAMs can affect the morphological changes, and enhance migration and invasion abilities of CC cells.

Conclusions

PD-L1 expression in tumor cells can be used as a prognostic factor and is closely related to CD163+TAMs infiltration. In addition, M2-type TAMs can upregulate PD-L1 expression in CC cells through PI3K/AKT pathway, enhance the migration and invasion capabilities, and affect the tumor progression.
Impact of high-altitude hypoxia on Helicobacter pylori-induced gastritis pathological manifestations and inflammatory responses
Authors: Li Chunxia , Wang Xuehong , Cui Sen
Published: July 2024

Background

Chronic gastritis caused by Helicobacter pylori (Hp) infection is a common gastrointestinal disorder. Despite the high prevalence of Hp infection and chronic gastritis in the Tibetan Plateau, there is a lack of studies elucidating the influence of plateau hypoxia on Hp-induced gastritis. This study aimed to investigate the impact of high-altitude hypoxia on Hp-induced gastritis, particularly focusing on pathological manifestations and inflammatory responses.

Methods

This study was conducted from July 2023 to March 2024 at the Department of Gastroenterology, Affiliated Hospital of Qinghai University. Ninety patients diagnosed with chronic gastritis were enrolled in the study and divided into four groups based on their residential altitude and Hp infection status. Data on endoscopic and pathological characteristics were collected, along with serum oxidative stress and inflammatory markers.

Results

Patients with Hp gastritis exhibit distinctive features in the gastric mucosa, including diffuse erythema, enlarged folds, and white turbid mucus during endoscopy. Notably, individuals with Hp gastritis at high altitudes show a higher prevalence of diffuse erythema and enlarged folds. Pathological analysis reveals that these patients have elevated gastric mucosal inflammation scores and increased chronic and active inflammation. Furthermore, individuals with Hp gastritis at high altitudes demonstrate elevated levels of serum TNF-α, IL-1β, IL-6, and MDA, as well as reduced serum SOD and GSH-Px activities.

Conclusions

High-altitude hypoxia may exacerbate gastric mucosal damage by enhancing oxidative stress and inflammatory response induced by Hp infection.