bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arsenic modifies the effect of folic acid in spina bifida prevention, a large hospital-based case-control study in Bangladesh
Authors: Wei Chih-Fu , Mukherjee Sudipta Kumer , Ekramullah Sheikh Muhammad , Arman D. M. , Islam Md Joynul , Azim Mubinul , Rahman Asifur , Rahman Md Nafaur , Ziauddin Md , Tindula Gwen , Suchanda Hafiza Sultana , Gomberg Diana F. , Weisskopf Marc G. , Liang Liming , Warf Benjamin C. , Christiani David C. , Mazumdar Maitreyi 
Published: June 2024

Abstract
Background
Spina bifida, a developmental malformation of the spinal cord, is associated with high rates of mortality and disability. Although folic acid-based preventive strategies have been successful in reducing rates of spina bifida, some areas continue to be at higher risk because of chemical exposures. Bangladesh has high arsenic exposures through contaminated drinking water and high rates of spina bifida. This study examines the relationships between mother’s arsenic exposure, folic acid, and spina bifida risk in Bangladesh.

Methods
We conducted a hospital-based case-control study at the National Institute of Neurosciences & Hospital (NINS&H) in Dhaka, Bangladesh, between December 2016 and December 2022. Cases were infants under age one year with spina bifida and further classified by a neurosurgeon and imaging. Controls were drawn from children seen at NINS&H and nearby Dhaka Shishu Hospital. Mothers reported folic acid use during pregnancy, and we assessed folate status with serum assays. Arsenic exposure was estimated in drinking water using graphite furnace atomic absorption spectrophotometry (GF-AAS) and in toenails using inductively coupled plasma mass spectrometry (ICP-MS). We used logistic regression to examine the associations between arsenic and spina bifida. We used stratified models to examine the associations between folic acid and spina bifida at different levels of arsenic exposure.

Results
We evaluated data from 294 cases of spina bifida and 163 controls. We did not find a main effect of mother’s arsenic exposure on spina bifida risk. However, in stratified analyses, folic acid use was associated with lower odds of spina bifida (adjusted odds ratio [OR]: 0.50, 95% confidence interval [CI]: 0.25-1.00, p = 0.05) among women with toenail arsenic concentrations below the median value of 0.46 µg/g, and no association was seen among mothers with toenail arsenic concentrations higher than 0.46 µg/g (adjusted OR: 1.09, 95% CI: 0.52–2.29, p = 0.82).

Conclusions
Mother’s arsenic exposure modified the protective association of folic acid with spina bifida. Increased surveillance and additional preventive strategies, such as folic acid fortification and reduction of arsenic, are needed in areas of high arsenic exposure.
Fertility-sparing uterine displacement for pelvic malignancies: surgical options and radiotherapy dosimetry on a human cadaver
Authors: Pavone Matteo , Waeldin Laure , Seeliger Barbara , Bizzarri Nicolò , Mutter Didier , Jarnet Delphine , Forgione Antonello , Georges Noel , Akladios Cherif , Scambia Giovanni , Marescaux Jacques , Lecointre Lise , Querleu Denis 
Published: June 2024

Abstract
Background
Radio(chemo)therapy is often required in pelvic malignancies (cancer of the anus, rectum, cervix). Direct irradiation adversely affects ovarian and endometrial function, compromising the fertility of women. While ovarian transposition is an established method to move the ovaries away from the radiation field, surgical procedures to displace the uterus are investigational. This study demonstrates the surgical options for uterine displacement in relation to the radiation dose received.

Methods
The uterine displacement techniques were carried out sequentially in a human female cadaver to demonstrate each procedure step by step and assess the uterine positions with dosimetric CT scans in a hybrid operating room. Two treatment plans (anal and rectal cancer) were simulated on each of the four dosimetric scans (1. anatomical position, 2. uterine suspension of the round ligaments to the abdominal wall 3. ventrofixation of the uterine fundus at the umbilical level, 4. uterine transposition). Treatments were planned on Eclipse® System (Varian Medical Systems®,USA) using Volumetric Modulated Arc Therapy. Data about maximum (Dmax) and mean (Dmean) radiation dose received and the volume receiving 14 Gy (V14Gy) were collected.

Results
All procedures were completed without technical complications. In the rectal cancer simulation with delivery of 50 Gy to the tumor, Dmax, Dmean and V14Gy to the uterus were respectively 52,8 Gy, 34,3 Gy and 30,5cc (1), 31,8 Gy, 20,2 Gy and 22.0cc (2), 24,4 Gy, 6,8 Gy and 5,5cc (3), 1,8 Gy, 0,6 Gy and 0,0cc (4). For anal cancer, delivering 64 Gy to the tumor respectively 46,7 Gy, 34,8 Gy and 31,3cc (1), 34,3 Gy, 20,0 Gy and 21,5cc (2), 21,8 Gy, 5,9 Gy and 2,6cc (3), 1,4 Gy, 0,7 Gy and 0,0cc (4).

Conclusions
The feasibility of several uterine displacement procedures was safely demonstrated. Increasing distance to the radiation field requires more complex surgical interventions to minimize radiation exposure. Surgical strategy needs to be tailored to the multidisciplinary treatment plan, and uterine transposition is the most technically complex with the least dose received.
Gasdermin D deficiency aborts myeloid calcium influx to drive granulopoiesis in lupus nephritis
Authors: Shen Jiani , Li Feng , Han Xu , Fu Dongying , Xu Yiping , Zhu Changjian , Liang Zhou , Tang Ziwen , Zheng Ruilin , Hu Xinrong , Lin Ruoni , Pei Qiaoqiao , Nie Jing , Luo Ning , Li Xiaoyan , Chen Wei , Mao Haiping , Zhou Yi , Yu Xueqing 
Published: June 2024

AbstractGasdermin D (GSDMD) is emerging as an important player in autoimmune diseases, but its exact role in lupus nephritis (LN) remains controversial. Here, we identified markedly elevated GSDMD in human and mouse LN kidneys, predominantly in CD11b+ myeloid cells. Global or myeloid-conditional deletion of GSDMD was shown to exacerbate systemic autoimmunity and renal injury in lupus mice with both chronic graft-versus-host (cGVH) disease and nephrotoxic serum (NTS) nephritis. Interestingly, RNA sequencing and flow cytometry revealed that myeloid GSDMD deficiency enhanced granulopoiesis at the hematopoietic sites in LN mice, exhibiting remarkable enrichment of neutrophil-related genes, significant increases in total and immature neutrophils as well as granulocyte/macrophage progenitors (GMPs). GSDMD-deficient GMPs and all-trans-retinoic acid (ATRA)-stimulated human promyelocytes NB4 were further demonstrated to possess enhanced clonogenic and differentiation abilities compared with controls. Mechanistically, GSDMD knockdown promoted self-renewal and granulocyte differentiation by restricting calcium influx, contributing to granulopoiesis. Functionally, GSDMD deficiency led to increased pathogenic neutrophil extracellular traps (NETs) in lupus peripheral blood and bone marrow-derived neutrophils. Taken together, our data establish that GSDMD deletion accelerates LN development by promoting granulopoiesis in a calcium influx-regulated manner, unraveling its unrecognized critical role in LN pathogenesis.
The transcriptional landscape of cancer stem-like cell functionality in breast cancer
Authors: Baldasici Oana , Soritau Olga , Roman Andrei , Lisencu Carmen , Visan Simona , Maja Laura , Pop Bogdan , Fetica Bogdan , Cismaru Andrei , Vlase Laurian , Balacescu Loredana , Balacescu Ovidiu , Russom Aman , Tudoran Oana 
Published: June 2024

Abstract
Background
Cancer stem-like cells (CSCs) have been extensively researched as the primary drivers of therapy resistance and tumor relapse in patients with breast cancer. However, due to lack of specific molecular markers, increased phenotypic plasticity and no clear clinicopathological features, the assessment of CSCs presence and functionality in solid tumors is challenging. While several potential markers, such as CD24/CD44, have been proposed, the extent to which they truly represent the stem cell potential of tumors or merely provide static snapshots is still a subject of controversy. Recent studies have highlighted the crucial role of the tumor microenvironment (TME) in influencing the CSC phenotype in breast cancer. The interplay between the tumor and TME induces significant changes in the cancer cell phenotype, leading to the acquisition of CSC characteristics, therapeutic resistance, and metastatic spread. Simultaneously, CSCs actively shape their microenvironment by evading immune surveillance and attracting stromal cells that support tumor progression.

Methods
In this study, we associated in vitro mammosphere formation assays with bulk tumor microarray profiling and deconvolution algorithms to map CSC functionality and the microenvironmental landscape in a large cohort of 125 breast tumors.

Results
We found that the TME score was a significant factor associated with CSC functionality. CSC-rich tumors were characterized by an immune-suppressed TME, while tumors devoid of CSC potential exhibited high immune infiltration and activation of pathways involved in the immune response. Gene expression analysis revealed IFNG, CXCR5, CD40LG, TBX21 and IL2RG to be associated with the CSC phenotype and also displayed prognostic value for patients with breast cancer.

Conclusion
These results suggest that the characterization of CSCs content and functionality in tumors can be used as an attractive strategy to fine-tune treatments and guide clinical decisions to improve patients therapy response.
Next-generation sequencing of primary testicular lymphoma and relapse in the glans penis after prophylactic radiation therapy: a rare case report
Authors: Ishibashi Naoya , Nakanishi Yoko , Maebayashi Toshiya , Miura Katsuhiro , Ohni Sumie , Masuda Shinobu , Amano Yasuo , Okada Masahiro 
Published: June 2024

Abstract
Background
Primary testicular lymphoma (PTL) is relatively rare. The contralateral testis is a common site of PTL relapse; therefore, once complete remission is achieved, radiation therapy (RT) is administered to the contralateral testis to prevent relapse.

Case presentation
A 76-year-old man was diagnosed with PTL and received RT as described above. However, despite achieving and maintaining complete remission, a mass diagnosed as diffuse large B-cell lymphoma by tissue biopsy developed in the glans penis 6.5 years after prophylactic RT. We investigated whether the glans penile lymphoma was PTL relapse or a new malignancy by genomic analysis using next-generation sequencing of DNA extracted from two histopathological specimens.

Conclusions
We found the same variant allele fraction in four somatic genes (MYD88, IL7R, BLNK, and FLT3) at similar frequencies, indicating that the glans penile lymphoma had the same origin as the PTL. To the best of our knowledge, this is the first case report of PTL relapse in the glans penis.
Chrysanthemum morifolium Ramat extract and probiotics combination ameliorates metabolic disorders through regulating gut microbiota and PPARα subcellular localization
Authors: Gao Xinxin , Zhu Zhigang , Bao Yiyang , Li Yifan , Zhu Weize , He Xiaofang , Ge Xinyu , Huang Wenjin , Wang Hao , Wei Wenjing , Du Jun , Chen Liang , Li Houkai , Sheng Lili 
Published: June 2024

Abstract
Background
Chrysanthemum morifolium Ramat, a traditional Chinese medicine, has the effects on liver clearing, vision improving, and anti-inflammation. C. morifolium and probiotics have been individually studied for their beneficial effects on metabolic diseases. However, the underlying molecular mechanisms were not completely elucidated. This study aims to elucidate the potential molecular mechanisms of C. morifolium and probiotics combination (CP) on alleviating nonalcoholic fatty liver disease (NAFLD) and the dysregulation of glucose metabolism in high-fat diet (HFD)-fed mice.

Methods
The therapeutic effect of CP on metabolism was evaluated by liver histology and serum biochemical analysis, as well as glucose tolerance test. The impact of CP on gut microbiota was analyzed by 16S rRNA sequencing and fecal microbiota transplantation. Hepatic transcriptomic analysis was performed with the key genes and proteins validated by RT-qPCR and western blotting. In addition, whole body Pparα knockout (Pparα−/−) mice were used to confirm the CP-mediated pathway.

Results
CP supplementation ameliorated metabolic disorders by reducing body weight and hepatic steatosis, and improving glucose intolerance and insulin resistance in HFD fed mice. CP intervention mitigated the HFD-induced gut microbiota dysbiosis, which contributed at least in part, to the beneficial effect of improving glucose metabolism. In addition, hepatic transcriptomic analysis showed that CP modulated the expression of genes associated with lipid metabolism. CP downregulated the mRNA level of lipid droplet-binding proteins, such as Cidea and Cidec in the liver, leading to more substrates for fatty acid oxidation (FAO). Meanwhile, the expression of CPT1α, the rate-limiting enzyme of FAO, was significantly increased upon CP treatment. Mechanistically, though CP didn’t affect the total PPARα level, it promoted the nuclear localization of PPARα, which contributed to the reduced expression of Cidea and Cidec, and increased expression of CPT1α, leading to activated FAO. Moreover, whole body PPARα deficiency abolished the anti-NAFLD effect of CP, suggesting the importance of PPARα in CP-mediated beneficial effect.

Conclusion
This study revealed the hypoglycemic and hepatoprotective effect of CP by regulating gut microbiota composition and PPARα subcellular localization, highlighting its potential for therapeutic candidate for metabolic disorders.
YY1 mediated DCUN1D5 transcriptional activation promotes triple-negative breast cancer progression by targeting FN1/PI3K/AKT pathway
Authors: Lin Yuxiang , Li Yan , Chen Xiaobin , Jin Xuan , Jiang Meichen , Xiao Han , Chen Lili , Chen Minyan , Zhang Wenzhe , Chen Hanxi , Nie Qian , Guo Rongrong , Guo Wenhui , Fu Fangmeng , Wang Chuan 
Published: June 2024

AbstractTriple-negative breast cancer (TNBC) is more aggressive and has a higher metastasis rate compared with other subtypes of breast cancer. Due to the lack of drug-targetable receptors, chemotherapy is now the only available systemic treatment for TNBC. However, some patients might still develop drug resistance and have poor prognosis. Therefore, novel molecular biomarkers and new treatment targets are urgently needed for patients with TNBC. To provide molecular insights into TNBC progression, we investigated the function and the underlying mechanism of Defective in cullin neddylation 1 domain containing 5 (DCUN1D5) in the regulation of TNBC. By TCGA dataset and surgical specimens with immunohistochemical (IHC) staining method, DCUN1D5 was identified to be significantly upregulated in TNBC tumor tissues and negatively associated with prognosis. A series of in vitro and in vivo experiments were performed to confirm the oncogenic role of DCUN1D5 in TNBC. Overexpression of FN1 or PI3K/AKT activator IGF-1 could restore the proliferative and invasive ability induced by DCUN1D5 knockdown and DCUN1D5 could act as a novel transcriptional target of transcription factor Yin Yang 1 (YY1). In conclusion, YY1-enhanced DCUN1D5 expression could promote TNBC progression by FN1/PI3K/AKT pathway and DCUN1D5 might be a potential prognostic biomarker and therapeutic target for TNBC treatment.
Effect of 2-hydroxyethylammonium carboxylate protic ionic liquids on the solubility and cytotoxicity of indomethacin
Authors: Akbarzadeh Gondoghdi Parisa , Khorsandi Mohammad , Mokhtarpour Masumeh , Shekaari Hemayat , Hamishehkar Hamed 
Published: June 2024

AbstractRecently, there is a particular interest to utilize protic ionic liquids (PILs) in drug solubility. This study is exploring the effect of three protic ionic liquids (PILs) based on 2-hydroxyethylammonium carboxylate [2-hydroxyethylammonium acetate (MEAA), 2-hydroxyethylammonium lactate (MEAL), and 2-hydroxyethylammonium propionate (MEAP)] on the solubility of the very poorly soluble drug in water, indomethacin (IMC). The shake flask method was used to measure the experimental solubility of IMC at the different temperatures range (298.15–313.15) K. The results demonstrate significantly enhancment the solubility of IMC in PILs compared to pure water, with an approximate increase of 200 times. The experimental solubility data have been correlated using the empirical models which showed the performance as the order: Modified Apelblat–Jouyban–Acree > Van’t Hoff–Jouyban–Acree > Modified Apelblat equations and also the performance for the Wilson model indicated as the order (absolute relative deviation): 2-hydroxyethylammonium acetate (3.030) > 2-hydroxyethylammonium propionate (3.239) > 2-hydroxyethylammonium lactate (7.665). Then the thermodynamic dissolution properties were obtained by usage of Gibbs and Van’t Hoff equations to investigate the thermodynamic behavior of the IMC in the aqueous solution PILs. Eventually, the cytotoxicity of the co-solvents (PILs) under study was evaluated using a standard MTT assay. The results showed that the cell viability percentage increased in the following order: MEAA < MEAP < MEAL. These findings indicated that these PILs had low to moderate toxicity. It is noteworthy that the functional groups of the anions were not the only determinant factor of the cytotoxicity. Other factors encompassing concentration, exposure time, and cell line characteristics also had significant effects.
Validity of the I‑FEED classification in assessing postoperative gastrointestinal impairment in patients undergoing elective lumbar spinal surgery with general anesthesia: a prospective observational study
Authors: Wu Chun-Yu , Lai Chih-Jun , Xiao Fu-Ren , Yang Jen-Ting , Yang Shih-Hung , Lai Dar-Ming , Tsuang Fon-Yih 
Published: June 2024

Abstract
Background
The I-FEED classification, scored 0–8, was reported to accurately describe the clinical manifestations of gastrointestinal impairment after colorectal surgery. Therefore, it is interesting to determine whether the I-FEED scoring system is also applicable to patients undergoing lumbar spine surgery.

Methods
Adult patients undergoing elective lumbar spine surgery were enrolled, and the I-FEED score was measured for 4 days after surgery. The I-FEED scoring system incorporates five elements: intake (score: 0, 1, 3), feeling nauseated (score: 0, 1, 3), emesis (score: 0, 1, 3), results of physical exam (score: 0, 1, 3), and duration of symptoms (score: 0, 1, 2). Daily I-FEED scores were summed, and the highest overall score is used to categorize patients into one of three categories: normal (0–2 points), postoperative gastrointestinal intolerance (POGI; 3–5 points), and postoperative gastrointestinal dysfunction (POGD; 6 + points). The construct validity hypothesis testing determines whether the I-FEED category is consistent with objective clinical findings relevant to gastrointestinal impairment, namely, the longer length of hospital stay (LOS), higher inhospital medical cost, more postoperative gastrointestinal medical treatment, and more postoperative non-gastrointestinal complications.

Results
A total of 156 patients were enrolled, and 25.0% of patients were categorized as normal, 49.4% POGI, and 25.6% POGD. Patients with higher I-FEED scores agreed with the four validity hypotheses. Patients with POGD had a significantly longer length of hospital stay (1 day longer median stay; p = 0.049) and more inhospital medical costs (approximately 500 Taiwanese dollars; p = 0.037), and more patients with POGD required rectal laxatives (10.3% vs. 32.5% vs. 32.5%; p = 0.026). In addition, more patients with POGD had non-gastrointestinal complications (5.1% vs. 11.7% vs. 30.0%; p = 0.034).

Conclusion
This study contributes preliminary validity evidence for the I-FEED score as a measure for postoperative gastrointestinal impairment after elective lumbar spine surgery.
Emilin2 marks the target region for mesenchymal cell accumulation in bone regeneration
Authors: Qing Yifan , Ono Takehito , Kohara Yukihiro , Watanabe Atsushi , Ogiso Noboru , Ito Masako , Nakashima Tomoki , Takeshita Sunao 
Published: June 2024

Abstract
Background
Regeneration of injured tissue is dependent on stem/progenitor cells, which can undergo proliferation and maturation processes to replace the lost cells and extracellular matrix (ECM). Bone has a higher regenerative capacity than other tissues, with abundant mesenchymal progenitor cells in the bone marrow, periosteum, and surrounding muscle. However, the treatment of bone fractures is not always successful; a marked number of clinical case reports have described nonunion or delayed healing for various reasons. Supplementation of exogenous stem cells by stem cell therapy is anticipated to improve treatment outcomes; however, there are several drawbacks including the need for special devices for the expansion of stem cells outside the body, low rate of cell viability in the body after transplantation, and oncological complications. The use of endogenous stem/progenitor cells, instead of exogenous cells, would be a possible solution, but it is unclear how these cells migrate towards the injury site.

Methods
The chemoattractant capacity of the elastin microfibril interface located protein 2 (Emilin2), generated by macrophages, was identified by the migration assay and LC–MS/MS. The functions of Emilin2 in bone regeneration were further studied using Emilin2–/– mice.

Results
The results show that in response to bone injury, there was an increase in Emilin2, an ECM protein. Produced by macrophages, Emilin2 exhibited chemoattractant properties towards mesenchymal cells. Emilin2–/– mice underwent delayed bone regeneration, with a decrease in mesenchymal cells after injury. Local administration of recombinant Emilin2 protein enhanced bone regeneration.

Conclusion
Emilin2 plays a crucial role in bone regeneration by increasing mesenchymal cells. Therefore, Emilin2 can be used for the treatment of bone fracture by recruiting endogenous progenitor cells.