bluuebunny/crossref_metadata_2025_split huggingface dataset:
PD-1/PD-L1 Interaction Upregulates YAP1 Expression in HepG2 Cells Through MAPK/ERK Pathway
Authors: Li Shenghao , Dai Muwei , Wang Fang , Hao Liyuan , Feng Caixia , Jia Yansheng , Li Yaoqi , Kang Xichun , Hu Xiaoyu , Yan Huimin 
Published: October 2023

Background Antibodies, which target programmed cell death protein-1 (PD-1) or its ligand programmed death ligand-1 (PD-L1), can rescue T cells from an exhausted state and resume their immune response to cancer cells. Clinically, the purpose of blocking the PD-1/PD-L1 signaling pathway is to induce immune cells to play an anti-tumor role. However, the effect of intertumor PD-1/PD-L1 signal blocking on tumor cells remains unclear. Methods HepG2 cells were treated with DHA, IFN-γ, BSA, DDP, PD-1-Fc (1 μg/ml), IgG-Fc, nivolumab, or human IgG for 24 h, respectively. GEPIA, cBioPortal, and TIMER databases were used to analyze the correlation between YAP1, PD-1, and PD-L1 and ERK, ERK-5, JNK, and p38. Western blot was used to detect the expression of YAP1 and p-ERK. Results GEPIA, cBioPortal, and TIMER databases analysis showed that YAP1 was positively correlated with ERK. After HepG2 cells were treated with PD98059 (ERK inhibitor), the expression of YAP1 was decreased. In this study, we investigated the inhibitory effect of PD98059 on PD-1/PD-L1 signaling. Our study found that PD-1-Fc (PD-1 fusion protein) promoted the expression of p-ERK/ERK and YAP1 in HepG2 cells. In contrast, nivolumab (PD-1 blocking antibody) reduced the expression of p-ERK/ERK and YAP1 in IFN-γ-pretreated HepG2 cells. In addition, the application of DHA also inhibited the expression of p-ERK/ERK to inhibit YAP1. Furthermore, treatment of HepG2 cells with DHA alone or DHA combined with cisplatin (DDP) both inhibited the expression of p-ERK/ERK and YAP1. Conclusions These results suggested that PD-1/PD-L1 interactions between tumor cells could promote the expression of ERK or YAP1 within tumors. Moreover, the conduction of PD-1/PD-L1 could be reversed using ERK inhibitors.
The nonessential amino acid cysteine is required to prevent ferroptosis in acute myeloid leukemia
Authors: Cunningham Alan , Oudejans Lieve L. , Geugien Marjan , Pereira-Martins Diego Antonio , Wierenga Albertus T. J. , Erdem Ayşegül , Sternadt Dominique , Huls Gerwin , Schuringa Jan Jacob 
Published: October 2023

Abstract
Cysteine is a nonessential amino acid required for protein synthesis, the generation of the antioxidant glutathione, and for synthesizing the nonproteinogenic amino acid taurine. Here, we highlight the broad sensitivity of leukemic stem and progenitor cells to cysteine depletion. By CRISPR/CRISPR-associated protein 9–mediated knockout of cystathionine-γ-lyase, the cystathionine-to-cysteine converting enzyme, and by metabolite supplementation studies upstream of cysteine, we functionally prove that cysteine is not synthesized from methionine in acute myeloid leukemia (AML) cells. Therefore, although perhaps nutritionally nonessential, cysteine must be imported for survival of these specific cell types. Depletion of cyst(e)ine increased reactive oxygen species (ROS) levels, and cell death was induced predominantly as a consequence of glutathione deprivation. nicotinamide adenine dinucleotide phosphate hydrogen oxidase inhibition strongly rescued viability after cysteine depletion, highlighting this as an important source of ROS in AML. ROS-induced cell death was mediated via ferroptosis, and inhibition of glutathione peroxidase 4 (GPX4), which functions in reducing lipid peroxides, was also highly toxic. We therefore propose that GPX4 is likely key in mediating the antioxidant activity of glutathione. In line, inhibition of the ROS scavenger thioredoxin reductase with auranofin also impaired cell viability, whereby we find that oxidative phosphorylation–driven AML subtypes, in particular, are highly dependent on thioredoxin-mediated protection against ferroptosis. Although inhibition of the cystine-glutamine antiporter by sulfasalazine was ineffective as a monotherapy, its combination with L-buthionine-sulfoximine (BSO) further improved AML ferroptosis induction. We propose the combination of either sulfasalazine or antioxidant machinery inhibitors along with ROS inducers such as BSO or chemotherapy for further preclinical testing.
FFT-Based Numerical Method for Nonlinear Elastic Contact
Authors: Guo Fei , Wu Fan , Li Xinyong , Huang Yijie , Wang Zhuo 
Published: October 2023

AbstractIn theoretical research pertaining to sealing, a contact model must be used to obtain the leakage channel. However, for elastoplastic contact, current numerical methods require a long calculation time. Hyperelastic contact is typically simplified to a linear elastic contact problem, which must be improved in terms of calculation accuracy. Based on the fast Fourier transform, a numerical method suitable for elastoplastic and hyperelastic frictionless contact that can be used for solving two-dimensional and three-dimensional (3D) contact problems is proposed herein. The nonlinear elastic contact problem is converted into a linear elastic contact problem considering residual deformation (or the equivalent residual deformation). Results from numerical simulations for elastic, elastoplastic, and hyperelastic contact between a hemisphere and a rigid plane are compared with those obtained using the finite element method to verify the accuracy of the numerical method. Compared with the existing elastoplastic contact numerical methods, the proposed method achieves a higher calculation efficiency while ensuring a certain calculation accuracy (i.e., the pressure error does not exceed 15%, whereas the calculation time does not exceed 10 min in a 64 × 64 grid). For hyperelastic contact, the proposed method reduces the dependence of the approximation result on the load, as in a linear elastic approximation. Finally, using the sealing application as an example, the contact and leakage rates between complicated 3D rough surfaces are calculated. Despite a certain error, the simplified numerical method yields a better approximation result than the linear elastic contact approximation. Additionally, the result can be used as fast solutions in engineering applications.
A case report of Cobb’s collar with posterior urethral valves: a rare entity
Authors: Hameed Farooq , Anwaar Adeel 
Published: October 2023

Abstract
Background
Posterior urethral valve (PUV) is a congenital disorder typically presenting in the neonatal period and is associated with the obstruction of the urinary tract. Cobb’s collar is congenital narrowing of bulbar urethra in infants. It can lead to significant morbidity, which may include irreversible renal failure if left untreated.

Case presentation
A 21-month-old child presented with acute retention of urine and distended lower abdomen. His baseline tests were normal. Ultrasound KUB showed grossly enlarged bladder with almost 1100-ml residual urine. Foley’s catheterization attempted but failed. Urgent cystoscopy was planned where congenital anterior urethral stricture with posterior urethral valves was seen. DVIU done for urethral stricture followed by fulguration of posterior urethral valves. The patient was discharged from hospital the next day.

Conclusion
A congenital narrowing of the bulbar urethra is uncommon. Though it is rare, it can occur concomitantly with PUV. If this double pathology is missed can result in serious consequences. Children with recurrent urinary tract infections should be ruled out for anterior urethral strictures.
Endoscopic iatrogenic esophageal perforation and management: a retrospective outcome analysis in the modern era
Authors: Montminy Eric M. , Jones Blake , Heller J. Christie , Attwell Augustin 
Published: October 2023

Abstract
Introduction
Iatrogenic esophageal perforation (IEP) is a severe adverse event (AE) of upper endoscopy procedures (UEPs) associated with morbidity. Management has shifted from surgery to endotherapy with clip closure (CC), self-expanding metal stent (SEMS), and vacuum therapy (VT). Limited analyses measure outcomes during contemporary interventional endoscopy periods.

Methods
IEPs associated with EGD, upper EUS, small bowel enteroscopy (SBE), and ERCP at a 3-hospital academic center from January 2011 to December 2023 were identified retrospectively from a centralized AE database. Additional information was obtained from medical records. Statistical analysis was performed using Microsoft Excel and STATA.

Results
Thirty-two IEPs from 26 EGDs, 4 EUS, 1 SBE, and 1 ERCP were identified. IEPs occurred mostly after dilation (bougie N = 7; balloon, N = 5) or foreign body removal (N = 6). Most IEPs occurred in the lower esophagus (N = 10) or gastroesophageal junction (N = 8). Diagnosis was made at a median 2 h after the injury by endoscopy (N = 14), CT scan (N = 12), esophagram (N = 5), or x-ray (N = 1). Initial treatment included conservative therapy alone (N = 7), CC (N = 3), SEMS (N = 14), SEMS plus CC (N = 3), or surgery (N = 3). Eleven patients required additional treatment including repeat SEMS or adjustment (N = 4) or VT (N = 1). No surgical interventions were required after 2013. The median hospital stay was 3 days. Disposition included discharge to home (N = 25), long-term care facility (N = 2), 4 deaths (12.5% of IEPs), and 1 unknown.

Conclusions
IEPs are rare and occur throughout the esophagus after any UEP. The majority are recognized immediately and managed with endotherapy, or rarely, surgery today. These characteristics likely explain the low mortality in this study.
Development and validation of a model for early diagnosis of biliary atresia
Authors: Gong Zongrong , Lin Lin , Lu Gen , Wan Chaomin 
Published: October 2023

Abstract
Background and aims
Early diagnosis of biliary atresia (BA), particularly distinguishing it from other causes of neonatal cholestasis (NC), is challenging. This study aimed to design and validate a predictive model for BA by using the data available at the initial presentation.

Methods
Infants presenting with NC were retrospectively identified from tertiary referral hospitals and constituted the model design cohort (n = 148); others were enrolled in a prospective observational study and constituted the validation cohort (n = 21). Clinical, laboratory, and abdominal ultrasonographic features associated with BA were assessed. A prediction model was developed using logistic regression and decision tree (DT) analyses.

Results
Three predictors, namely, gamma glutamyl transpeptidase (γGT) level, triangular cord sign (TC sign), and gallbladder abnormalities, were identified as factors for diagnosing BA in multivariate logistic regression, which was used to develop the DT model. The area under the receiver operating characteristic (ROC) curve (AUC) value for the model was 0.905, which was greater than those for γGT level, TC sign, or gallbladder abnormalities alone in the prediction of BA.

Conclusion
A simple prediction model combining liver function and abdominal ultrasonography findings can provide a moderate and early estimate of the risk of BA in patients with NC.
My virtual home: needs of patients in palliative cancer care and content effects of individualized virtual reality – a mixed methods study protocol
Authors: Gerlach Christina , Greinacher Anja , Alt-Epping Bernd , Wrzus Cornelia 
Published: October 2023

Abstract
Background
The desire to be at home is one of the most important needs of patients with advanced, incurable cancers. However, palliative cancer patients may require inpatient hospital care for medical reasons. Virtual reality (VR) could provide an approximation to the individuals’ home environment.

Methods
The project consists of 3 parts. All parts are supported by the patient advisory board. In the 1st part of the project, we interview patients, relatives, and the patient advisory board about their wishes and concerns regarding the project. In the 2nd part of the project, patients are offered to view 360° VR videos of their choice (their home, relatives, others if applicable). Effects and side-effects of the intervention are assessed with validated instruments (MIDOS, MDBF, SSQ, SPES). Diagnosis, treatment adherence, medication, and vegetative functionality is determined from the medical records of the patients. In the 3rd part of the project, the results of the study will be discussed with patients, relatives, health care professionals and the patient advisory board regarding implementation.

Discussion
This study is the first to investigate whether individualized VR videos have additional benefits over generic VR nature videos on symptom relief, well-being, treatment satisfaction, and adherence in patients with palliative cancer care. A strength of the study is that we can incorporate the results of each part of the project into the subsequent project parts. However, the generalizability might be limited as this is a single-centred study.

Trial registration
Registered at German Clinical Trials Register (Deutsches Register Klinischer Studien; DRKS); registration number: DRKS00032172; registration date: 11/07/2023 https://drks.de/search/de/trial/DRKS00032172.
Perception of the professional self-image by nurses and midwives. Psychometric adaptation of the Belimage questionnaire
Authors: Stadnicka Sabina Katarzyna , Zarzycka Danuta 
Published: October 2023

Abstract
Background
The aim of this paper is to present the research results on the perception of the professional self-image by Polish nurses and midwives as well as the psychometric adaptation of the Belimage scale.

Methods
A cross-sectional survey was conducted from January to November 2018. The study group consisted of 670 clinical practice nurses and midwives. A diagnostic survey method was applied using the Belimage questionnaire after it obtained acceptable psychometric properties through an adaptation procedure.

Results
In the group of respondents, the professional image of nurses and midwives is dominated by instrumental skills, documentation and organization of care, and communication skills. There is a statistically significant difference in the image of these two professions in terms of the ability to think and act creatively and critically, as well as innovation and evidence-based practice. The respondents' opinion regarding the perception of their image by themselves and society is statistically significant in each of the analyzed areas. In the professional image created by the public, nurses and midwives recognize that being a nurse/midwife is a vocation—277 (41.3%). However, in terms of their self-image, most nurses and midwives consider their work to be hard—442 (66%) and poorly paid—445 (66.4%). In the psychometric validation process, the Belimage questionnaire retained the original item structure, and the reliability of the subscales assessed with the Cronbach's alpha coefficient ranged from 0.845 to 0.730.

Conclusions
The professional image of nurses and midwives varies depending on the profession and the perspective of the assessment in relation to themselves and society. The study showed a particularly unfavorable social image of nurses and midwives, which significantly influences the outlook of nurses and midwives themselves on this issue.
A mixed-methods study of the awareness and functionality of sexual and reproductive health services among persons with disability in Ghana
Authors: Seidu Abdul-Aziz , Malau-Aduli Bunmi S. , McBain-Rigg Kristin , Malau-Aduli Aduli E. O. , Emeto Theophilus I. 
Published: October 2023

Abstract
Background
Persons with disabilities (PwDs) face barriers in accessing sexual and reproductive health (SRH) services due to lack of knowledge and awareness, stigma and discrimination, and inadequate service provision. This study aimed to examine the determinants of SRH knowledge and awareness among PwDs in Ghana, and to explore their perceptions of the functionality of SRH services.

Methods
A sequential explanatory mixed-methods study design was used to collect and analyse quantitative (n = 402) and qualitative (n = 37) data from PwDs in two districts in Ghana. Quantitative data were analysed using descriptive and inferential statistics, while qualitative data was analysed thematically.

Results
Most of the participants had high awareness of SRH (94.3%), sexually transmitted infections (STIs) (92.5%) and HIV/AIDS (97.0%). Employment status was positively associated with SRH awareness [aOR = 1.62; 95% CI = 1.02, 2.59]. Disability type was a significant predictor of STI [aOR = 2.02; 95% CI = 1.39, 2.94] and HIV/AIDS [aOR = 2.32; 95% CI = 1.21, 4.44] awareness, with the visually impaired having higher odds than the physically disabled. Age group was also a significant predictor of STI awareness, with older respondents having higher odds than younger ones [aOR = 1.76; CI = 1.01,3.05 for 30–39 years; aOR = 2.48; CI = 1.22, 5.05 for 40–49 years]. The qualitative findings revealed four main themes: conceptualisation of SRH, active engagement in SRH information seeking, tensions between knowledge and religious beliefs and perceived utility of SRH services.

Conclusion
Despite the high levels of SRH knowledge and awareness among PwDs, there are significant gaps and challenges related to disability type, age group, misconceptions, beliefs, and service non-functionality that limit the utility of SRH services. The findings call for tailored education to reduce misconceptions and put in pragmatic steps to deliver quality SRH services and information to PwDs. Further research is needed to assess the sexual lives of PwDs and explore the perspectives of all relevant stakeholders, including service providers and policymakers on how to enhance SRH outcomes for PwDs in Ghana.
Chromosome 1p36 candidate gene ZNF436 predicts the prognosis of neuroblastoma: a bioinformatic analysis
Authors: Wang Haiwei , Wang Xinrui , Xu Liangpu 
Published: October 2023

Abstract
Background
Genetic 1p deletion is reported in 30% of all neuroblastoma and is associated with the unfavorable prognosis of neuroblastoma. The expressions and prognosis of 1p candidate genes in neuroblastoma are unclear.

Methods
Public neuroblastoma cohorts were obtained for secondary analysis. The prognosis of 1p candidate genes in neuroblastoma was determined using Kaplan-Meier and cox regression analysis. The prediction of the nomogram model was determined using timeROC.

Results
First, we confirmed the bad prognosis of 1p deletion in neuroblastoma. Moreover, zinc finger protein 436 (ZNF436) located at 1p36 region was down-regulated in 1p deleted neuroblastoma and higher ZNF436 expression was associated with the longer event free survival and overall survival of neuroblastoma. The expression levels of ZNF436 were lower in neuroblastoma patients with MYCN amplification or age at diagnosis ≥ 18months, or with stage 4 neuroblastoma. ZNF436 had robust predictive values of MYCN amplification and overall survival of neuroblastoma. Furthermore, the prognostic significance of ZNF436 in neuroblastoma was independent of MYCN amplification and age of diagnosis. Combinations of ZNF436 with MYCN amplification or age of diagnosis achieved better prognosis. At last, we constructed a nomogram risk model based on age, MYCN amplification and ZNF436. The nomogram model could predict the overall survival of neuroblastoma with high specificity and sensitivity.

Conclusions
Chromosome 1p36 candidate gene ZNF436 was a prognostic maker of neuroblastoma.
The pipeline for drugs for control and elimination of neglected tropical diseases: 2. Oral anti-infective drugs and drug combinations for off-label use
Authors: Pfarr Kenneth M. , Krome Anna K. , Al-Obaidi Issraa , Batchelor Hannah , Vaillant Michel , Hoerauf Achim , Opoku Nicholas O. , Kuesel Annette C. 
Published: October 2023

AbstractIn its ‘Road map for neglected tropical diseases 2021–2030’, the World Health Organization outlined its targets for control and elimination of neglected tropical diseases (NTDs) and research needed to achieve them. For many NTDs, this includes research for new treatment options for case management and/or preventive chemotherapy. Our review of small-molecule anti-infective drugs recently approved by a stringent regulatory authority (SRA) or in at least Phase 2 clinical development for regulatory approval showed that this pipeline cannot deliver all new treatments needed. WHO guidelines and country policies show that drugs may be recommended for control and elimination for NTDs for which they are not SRA approved (i.e. for ‘off-label’ use) if efficacy and safety data for the relevant NTD are considered sufficient by WHO and country authorities. Here, we are providing an overview of clinical research in the past 10 years evaluating the anti-infective efficacy of oral small-molecule drugs for NTD(s) for which they are neither SRA approved, nor included in current WHO strategies nor, considering the research sponsors, likely to be registered with a SRA for that NTD, if found to be effective and safe. No such research has been done for yaws, guinea worm, Trypanosoma brucei gambiense human African trypanosomiasis (HAT), rabies, trachoma, visceral leishmaniasis, mycetoma, T. b. rhodesiense HAT, echinococcosis, taeniasis/cysticercosis or scabies. Oral drugs evaluated include sparfloxacin and acedapsone for leprosy; rifampicin, rifapentin and moxifloxacin for onchocerciasis; imatinib and levamisole for loiasis; itraconazole, fluconazole, ketoconazole, posaconazole, ravuconazole and disulfiram for Chagas disease, doxycycline and rifampicin for lymphatic filariasis; arterolane, piperaquine, artesunate, artemether, lumefantrine and mefloquine for schistosomiasis; ivermectin, tribendimidine, pyrantel, oxantel and nitazoxanide for soil-transmitted helminths including strongyloidiasis; chloroquine, ivermectin, balapiravir, ribavirin, celgosivir, UV-4B, ivermectin and doxycycline for dengue; streptomycin, amoxicillin, clavulanate for Buruli ulcer; fluconazole and isavuconazonium for mycoses; clarithromycin and dapsone for cutaneous leishmaniasis; and tribendimidine, albendazole, mebendazole and nitazoxanide for foodborne trematodiasis. Additional paths to identification of new treatment options are needed. One promising path is exploitation of the worldwide experience with ‘off-label’ treatment of diseases with insufficient treatment options as pursued by the ‘CURE ID’ initiative.
Graphical abstract