bluuebunny/crossref_metadata_2025_split huggingface dataset:
The FACT-targeted drug CBL0137 enhances the effects of rituximab to inhibit B-cell non-Hodgkin’s lymphoma tumor growth by promoting apoptosis and autophagy
Authors: Lv Yan , Du Yuxin , Li Kening , Ma Xiao , Wang Juan , Du Tongde , Ma Yuxin , Teng Yue , Tang Weiyan , Ma Rong , Wu Jianqiu , Wu Jianzhong , Feng Jifeng 
Published: January 2023

Abstract
Background
Aggressive B-cell non-Hodgkin’s lymphoma (B-NHL) patients often develop drug resistance and tumor recurrence after conventional immunochemotherapy, for which new treatments are needed.

Methods
We investigated the antitumor effects of CBL0137. In vitro, cell proliferation was assessed by CCK-8 and colony formation assay. Flow cytometry was performed to analyze cell cycle progression, apoptosis, mitochondrial depolarization, and reactive oxygen species (ROS) production. Autophagy was detected by transmission electron microscopy and mGFP-RFP-LC3 assay, while western blotting was employed to detect proteins involved in apoptosis and autophagy. RNA-sequencing was conducted to analyze the transcription perturbation after CBL0137 treatment in B-NHL cell lines. Finally, the efficacy and safety of CBL0137, rituximab, and their combination were tested in vivo.

Results
CBL0137, a small molecule anticancer agent that has significant antitumor effects in B-NHL. CBL0137 sequesters the FACT (facilitates chromatin transcription) complex from chromatin to produce cytotoxic effects in B-NHL cells. In addition, we discovered novel anticancer mechanisms of CBL0137. CBL0137 inhibited human B-NHL cell proliferation by inducing cell cycle arrest in S phase via the c-MYC/p53/p21 pathway. Furthermore, CBL0137 triggers ROS generation and induces apoptosis and autophagy in B-NHL cells through the ROS-mediated PI3K/Akt/mTOR and MAPK signaling pathways. Notably, a combination of CBL0137 and rituximab significantly suppressed B-NHL tumor growth in subcutaneous models, consistent with results at the cellular level in vitro.

Conclusions
CBL0137 has potential as a novel approach for aggressive B-NHL, and its combination with rituximab can provide new therapeutic options for patients with aggressive B-NHL.
Resistin-like molecules: a marker, mediator and therapeutic target for multiple diseases
Authors: Shi Yaning , Zhu Neng , Qiu Yun , Tan Junlan , Wang Feiying , Qin Li , Dai Aiguo 
Published: January 2023

AbstractResistin-like molecules (RELMs) are highly cysteine-rich proteins, including RELMα, RELMβ, Resistin, and RELMγ. However, RELMs exhibit significant differences in structure, distribution, and function. The expression of RELMs is regulated by various signaling molecules, such as IL-4, IL-13, and their receptors. In addition, RELMs can mediate numerous signaling pathways, including HMGB1/RAGE, IL-4/IL-4Rα, PI3K/Akt/mTOR signaling pathways, and so on. RELMs proteins are involved in wide range of physiological and pathological processes, including inflammatory response, cell proliferation, glucose metabolism, barrier defense, etc., and participate in the progression of numerous diseases such as lung diseases, intestinal diseases, cardiovascular diseases, and cancers. Meanwhile, RELMs can serve as biomarkers, risk predictors, and therapeutic targets for these diseases. An in-depth understanding of the role of RELMs may provide novel targets or strategies for the treatment and prevention of related diseases.
Observation of the delineation of the target volume of radiotherapy in adult-type diffuse gliomas after temozolomide-based chemoradiotherapy: analysis of recurrence patterns and predictive factors
Authors: Liu Hongbo , Zhang Lu , Tan Ye , Jiang Yanxia , Lu Haijun 
Published: January 2023

Abstract
Background
Radiation therapy is the cornerstone of treatment for adult-type diffuse gliomas, but recurrences are inevitable. Our study assessed the prognosis and recurrence pattern of different radiotherapy volumes after temozolomide-based chemoradiation in our institution.

Methods
The treatment plans were classified into two groups, the plan 1 intentionally involved the entire edema area while plan 2 did not. Retrospectively investigate the differences in outcomes of 118 adult-type diffuse gliomas patients between these two treatment plans. Then, patients who underwent relapse were selected to analyze their recurrence patterns. Continuous dynamic magnetic resonance images (MRI) were collected to categorized the recurrence patterns into central, in-field, marginal, distant, and cerebrospinal fluid dissemination (CSF-d) recurrence. Finally, the clinical and molecular characteristics which influenced progression were analyzed.

Results
Plan 1 (n = 63) showed a median progression-free survival (PFS) and overall survival (OS) of 9.5 and 26.4 months while plan 2 (n = 55) showed a median PFS and OS of 9.4 and 36.5 months (p = 0.418; p = 0.388). Treatment target volume had no effect on the outcome in patients with adult-type diffuse gliomas. And there was no difference in radiation toxicity (p = 0.388). Among the 90 relapsed patients, a total of 58 (64.4%) patients had central recurrence, 10 (11.1%) patients had in-field recurrence, 3 (3.3%) patients had marginal recurrence, 11 (12.2.%) patients had distant recurrence, and 8 (8.9%) patients had CSF-d recurrence. By treatment plans, the recurrence patterns were similar and there was no significant difference in survival. Reclassifying the progression pattern into local and non-local groups, we observed that oligodendroglioma (n = 10) all relapsed in local and no difference in PFS and OS between the two groups (p > 0.05). Multivariable analysis showed that subventricular zone (SVZ) involvement was the independent risk factor for non-local recurrence in patients with GBM (p < 0.05).

Conclusion
In our study, deliberately including or not the entire edema had no impact on prognosis and recurrence. Patients with varied recurrence patterns had diverse clinical and genetic features.
Education as a protective factor for mental health risks among youth living in highly dangerous regions in Afghanistan
Authors: Kovess-Masfety V. , Frounfelker R. L. , Keyes K. , Karam E. , Sabawoon Ajmal , Sarwari Bashir Ahmad , Husky M. , Kaur N. , Rousseau C. 
Published: January 2023

AbstractBackgroundChildren in Afghanistan live in dangerous areas, and have been exposed to traumatic events and chaotic education. Progress has been made on access to education for girls who were the most affected by traditional attitudes against engagement in education.ObjectivesThe objectives were to evaluate the mental health of Afghan children living in regions of conflict and the association of mental health with school attendance for girls and boys.MethodThe study included 2707 school aged children in eight regions of Afghanistan (16 provinces) residing in households recruited through a multi-stage stratified cluster sampling strategy in 2017. The level of terrorist threat was evaluated by the intensity of terrorist attacks recorded that year in each province. Child mental health was assessed with the parental report Strengths and Difficulties Questionnaire (SDQ) along with information on school attendance, sociodemographic characteristics and geographic location.ResultsA total of 52.75% of children had scores above threshold for the SDQ total difficulties score, 39.19% for emotional difficulties, 51.98% for conduct challenges, and 15.37% for hyperactivity/inattention. Peer relationship problems were high (82.86%) and 12.38% reported that these problems impacted daily life. The level of terrorist threat was associated with SDQ total difficulties (Adjusted Odds Ratio [AOR] = 4.08, P < 0.0001), with youth in regions with high levels of terrorist threat more likely to have problems than youth in regions with low or medium levels of danger, independent of region and ethnicity. School attendance was negatively associated with emotional symptoms (AOR = 0.65, P < 0.0001) and mental health difficulties with impairment (AOR = 0.67, P = 0.007), but positively associated with peer relationships difficulties (AOR = 1.96, P > 0.0001). Conduct (AOR = 1.66, P < .0001) and SDQ total difficulties (AOR = 1.22, P = 0.019) were higher among boys. Overall, gender did not modify the relationship between school attendance and child mental health.ConclusionAttending school is essential for children’s mental health, across gender, and should be supported as a priority in Afghanistan despite the return of the Taliban.
Mesothelioma-associated fibroblasts enhance proliferation and migration of pleural mesothelioma cells via c-Met/PI3K and WNT signaling but do not protect against cisplatin
Authors: Ries Alexander , Flehberger Daniela , Slany Astrid , Pirker Christine , Mader Johanna C. , Mohr Thomas , Schelch Karin , Sinn Katharina , Mosleh Berta , Hoda Mir Alireza , Dome Balazs , Dolznig Helmut , Krupitza Georg , Müllauer Leonhard , Gerner Christopher , Berger Walter , Grusch Michael 
Published: January 2023

Abstract
Background
Pleural mesothelioma (PM) is an aggressive malignancy with poor prognosis. Unlike many other cancers, PM is mostly characterized by inactivation of tumor suppressor genes. Its highly malignant nature in absence of tumor driving oncogene mutations indicates an extrinsic supply of stimulating signals by cells of the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are an abundant cell type of the TME and have been shown to drive the progression of several malignancies. The aim of the current study was to isolate and characterize patient-derived mesothelioma-associated fibroblasts (Meso-CAFs), and evaluate their impact on PM cells.

Methods
Meso-CAFs were isolated from surgical specimens of PM patients and analyzed by array comparative genomic hybridization, next generation sequencing, transcriptomics and proteomics. Human PM cell lines were retrovirally transduced with GFP. The impact of Meso-CAFs on tumor cell growth, migration, as well as the response to small molecule inhibitors, cisplatin and pemetrexed treatment was investigated in 2D and 3D co-culture models by videomicroscopy and automated image analysis.

Results
Meso-CAFs show a normal diploid genotype without gene copy number aberrations typical for PM cells. They express CAF markers and lack PM marker expression. Their proteome and secretome profiles clearly differ from normal lung fibroblasts with particularly strong differences in actively secreted proteins. The presence of Meso-CAFs in co-culture resulted in significantly increased proliferation and migration of PM cells. A similar effect on PM cell growth and migration was induced by Meso-CAF-conditioned medium. Inhibition of c-Met with crizotinib, PI3K with LY-2940002 or WNT signaling with WNT-C59 significantly impaired the Meso-CAF-mediated growth stimulation of PM cells in co-culture at concentrations not affecting the PM cells alone. Meso-CAFs did not provide protection of PM cells against cisplatin but showed significant protection against the EGFR inhibitor erlotinib.

Conclusions
Our study provides the first characterization of human patient-derived Meso-CAFs and demonstrates a strong impact of Meso-CAFs on PM cell growth and migration, two key characteristics of PM aggressiveness, indicating a major role of Meso-CAFs in driving PM progression. Moreover, we identify signaling pathways required for Meso-CAF-mediated growth stimulation. These data could be relevant for novel therapeutic strategies against PM.
Single-nucleus RNA sequencing and deep tissue proteomics reveal distinct tumour microenvironment in stage-I and II cervical cancer
Authors: Liu Xiaosong , Ni Guoying , Zhang Pingping , Li Hejie , Li Junjie , Cavallazzi Sebold Bernardo , Wu Xiaolian , Chen Guoqiang , Yuan Songhua , Wang Tianfang 
Published: January 2023

Abstract
Background
Cervical cancer (CC) is the 3rd most common cancer in women and the 4th leading cause of deaths in gynaecological malignancies, yet the exact progression of CC is inconclusive, mainly due to the high complexity of the changing tumour microenvironment (TME) at different stages of tumorigenesis. Importantly, a detailed comparative single-nucleus transcriptomic analysis of tumour microenvironment (TME) of CC patients at different stages is lacking.

Methods
In this study, a total of 42,928 and 29,200 nuclei isolated from the tumour tissues of stage-I and II CC patients and subjected to single-nucleus RNA sequencing (snRNA-seq) analysis. The cell heterogeneity and functions were comparatively investigated using bioinformatic tools. In addition, label-free quantitative mass spectrometry based proteomic analysis was carried out. The proteome profiles of stage-I and II CC patients were compared, and an integrative analysis with the snRNA-seq was performed.

Results
Compared with the stage-I CC (CCI) patients, the immune response relevant signalling pathways were largely suppressed in various immune cells of the stage-II CC (CCII) patients, yet the signalling associated with cell and tissue development was enriched, as well as metabolism for energy production suggested by the upregulation of genes associated with mitochondria. This was consistent with the quantitative proteomic analysis that showed the dominance of proteins promoting cell growth and intercellular matrix development in the TME of CCII group. The interferon-α and γ responses appeared the most activated pathways in many cell populations of the CCI patients. Several collagens, such as COL12A1, COL5A1, COL4A1 and COL4A2, were found significantly upregulated in the CCII group, suggesting their roles in diagnosing CC progression. A novel transcript AC244205.1 was detected as the most upregulated gene in CCII patients, and its possible mechanistic role in CC may be investigated further.

Conclusions
Our study provides important resources for decoding the progression of CC and set the foundation for developing novel approaches for diagnosing CC and tackling the immunosuppressive TME.
Management of Borderline ovarian tumors (BOT): results of a retrospective, single center study in Switzerland
Authors: Kipp B. , Vidal A. , Lenick D. , Christmann-Schmid C. 
Published: January 2023

Abstract
Background
Borderline tumors are malignant epithelial ovarian tumors with a very low incidence. Thus experience in diagnostics and treatment is still rare. The aim of this study was to present and analyze data of women with borderline ovarian tumor (BOT) regarding clinical features, histological characteristics, diagnostics and treatment management.

Methods
In this single center retrospective study women with BOT treated at the Departement of Gynecology and Obstetrics at the Kantonsspital Luzern between 2011 and 2018 were analyzed according to their clinical and histological reports.

Results
A total of 42 women were enrolled. The median age was 58.5 with a range from 26 to 85, of which 31 (73.8%) were postmenopausal. Regarding the histological subtypes, 23 women (54.8%) had serous and 15 (35.7%) had mucinous BOT. Seromucinous histology was found in 3 patients (7.1%) and endometrioid in 1 woman (2.4%), respectively. All women underwent surgery. In a total of 39 women (92.9%) a complete surgical staging for BOT was performed. In 29 women (69.0%) staging was performed by laparoscopy, 13 (31.0%) underwent laparotomy. The mean follow up was 52 months (range = 16.3–101.4 months). During this period two patients, initially diagnosed in FIGO stage 1, recurred after 21.7 and 44 months, respectively, the second woman died after 53 months because of the BOT.

Conclusion
In the present study women were treated according to the international therapy recommendations and the rate of recurrence was very low. The most common risk factors for relapse are known to be FIGO stage, incomplete staging and peritoneal implants but were not present in our group. Thus further studies are necessary to investigate additional recurrence risks.
Index theory and multiple solutions for asymptotically linear second-order delay differential equations
Authors: Shan Yuan 
Published: January 2023

AbstractThis paper is concerned with the existence of periodic solutions for asymptotically linear second-order delay differential equations. We will establish an index theory for the linear system directly in the sense that we do not need to change the problem of the original linear system into the problem of an associated Hamiltonian system. By using the critical point theory and the index theory, some new existence results are obtained.
Impact of nutrition counseling on anthropometry and dietary intake of multiple sclerosis patients at Kasr Alainy Multiple Sclerosis Unit, Cairo, Egypt 2019–2020: randomized controlled clinical trial
Authors: Afifi Zeinab , Hassan Amr , Abdelrahman Nebal , El Sayed Asmaa , Salem Marwa 
Published: January 2023

Abstract
Background
Faulty dietary habits and overnutrition are prevalent among Egyptian patients with multiple sclerosis (MS) who do not receive nutrition care as part of treatment. Thus, this study was conducted to identify the effect of nutrition counseling on the nutritional status of patients with MS. This endeavor might provide evidence for the value of counseling in such a setting and advance the integration of nutrition counseling into the routine management of patients with MS.

Methods
A single-blinded, parallel-randomized controlled clinical trial was conducted at Kasr Alainy MS Unit on 120 eligible patients with MS from September 2019 to February 2020. Patients were randomly allocated to either the nutrition counseling intervention group (IG) or the control group (CG). Allocation concealment was performed by using sequentially numbered opaque sealed envelopes. All patients were assessed initially and complied with the Kasr Alainy MS Unit standard management protocol for the study period. Only patients in the IG underwent initial nutrition counseling sessions followed by a monthly evaluation. All patients were assessed at the end of the 3-month follow-up period. Sociodemographic data were gathered through a structured interview. Nutritional status was assessed anthropometrically and via 24-h recall. The 2 groups were compared initially and at the end of the follow-up. Both intention-to-treat and per-protocol analyses were conducted.

Results
At baseline assessment, the prevalence of overweight and obesity was 31.7% and 32.5%, respectively, and the mean body mass index was 27.7 ± 5.7 kg/m2. Mean waist circumference was 93.5 ± 11.9 and 99.2 ± 13.1 cm for males and females, respectively. Approximately 27.3% of males and 83.9% of females showed abdominal obesity. After 3 months of counseling, weight, body mass index, waist circumference, nutrient intake and adequacy significantly improved in the IG (p < 0.05).

Conclusion
Nutrition counseling significantly improved anthropometric measurements, dietary habits, nutrient intake and adequacy.

Trial registration
The study was registered on ClinicalTrial.gov and was given a code (NCT04217564).
Ubiquitin protein E3 ligase ASB9 suppresses proliferation and promotes apoptosis in human spermatogonial stem cell line by inducing HIF1AN degradation
Authors: Li Ning , Zhou Qianyin , Yi Zhang , Zhang Huan , Zhou Dai 
Published: January 2023

AbstractBackgroundSpermatogonial stem cells (SSCs) are critical for sustaining spermatogenesis. Even though several regulators of SSC have been identified in rodents, the regulatory mechanism of SSC in humans has yet to be discovered.MethodsTo explore the regulatory mechanisms of human SSCs, we analyzed publicly available human testicular single-cell sequencing data and found that Ankyrin repeat and SOCS box protein 9 (ASB9) is highly expressed in SSCs. We examined the expression localization of ASB9 using immunohistochemistry and overexpressed ASB9 in human SSC lines to explore its role in SSC proliferation and apoptosis. Meanwhile, we used immunoprecipitation to find the target protein of ASB9 and verified its functions. In addition, we examined the changes in the distribution of ASB9 in non-obstructive azoospermia (NOA) patients using Western blot and immunofluorescence.ResultsThe results of uniform manifold approximation and projection (UMAP) clustering and pseudotime analysis showed that ASB9 was highly expressed in SSCs, and its expression gradually increased during development. The immunohistochemical and dual-color immunofluorescence results displayed that ASB9 was mainly expressed in nonproliferating SSCs. Overexpression of ASB9 in the SSC line revealed significant inhibition of cell proliferation and increased apoptosis. We predicted the target proteins of ASB9 and verified that hypoxia-inducible factor 1-alpha inhibitor (HIF1AN), but not creatine kinase B-type (CKB), has a direct interaction with ASB9 in human SSC line using protein immunoprecipitation experiments. Subsequently, we re-expressed HIF1AN in ASB9 overexpressing cells and found that HIF1AN reversed the proliferative and apoptotic changes induced by ASB9 overexpression. In addition, we found that ABS9 was significantly downregulated in some NOA patients, implying a correlation between ASB9 dysregulation and impaired spermatogenesis.ConclusionASB9 is predominantly expressed in human SSCs, it affects the proliferation and apoptotic process of the SSC line through HIF1AN, and its abnormal expression may be associated with NOA.
Gangrenous ischemic colitis localized to the cecum: a case report
Authors: Tateno Kohei , Motegi Yoko , Ogawa Hiroomi , Suga Kunihiko , Okada Takuhisa , Osone Katsuya , Katoh Ryuji , Ubukata Yasunari , Saito Hideyuki , Hara Keigo , Sakai Makoto , Ogata Kyoichi , Sohda Makoto , Murakami Chiaki , Shirabe Ken , Saeki Hiroshi 
Published: January 2023

Abstract
Background
Ischemic colitis affects the left colon in elderly individuals and localization on the right side, especially in the cecum, is rare. We report a case of gangrenous ischemic colitis localized in the cecum of a patient undergoing hemodialysis.

Case presentation
A 73-year-old man had been undergoing hemodialysis for chronic renal failure caused by diabetic nephropathy. He experienced frequent vomiting, diarrhea, and abdominal pain. Contrast-enhanced computed tomography revealed thickening of the cecal wall, poor enhancement, dilation of the cecum, and intrahepatic portal emphysema. No obvious abnormal findings were observed in the appendix. The patient was diagnosed with cecal necrosis and ileocecal resection was performed. Histopathological examination revealed gangrenous ischemic colitis of the cecum. He was discharged 12 days after surgery without postoperative complications.

Conclusion
It is important to consider the possibility of ischemic colitis of the right colon in the event of renal failure requiring dialysis, to ensure that opportunities for surgical intervention are not missed.