bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthetic lethality of combined ULK1 defection and p53 restoration induce pyroptosis by directly upregulating GSDME transcription and cleavage activation through ROS/NLRP3 signaling
Authors: Chen Wei , Yang Kai-Bin , Zhang Yuan-Zhe , Lin Zai-Shan , Chen Jin-Wei , Qi Si-Fan , Wu Chen-Fei , Feng Gong-Kan , Yang Da-Jun , Chen Ming , Zhu Xiao-Feng , Li Xuan 
Published: August 2024

Abstract
Background
High expression of ubiquitin ligase MDM2 is a primary cause of p53 inactivation in many tumors, making it a promising therapeutic target. However, MDM2 inhibitors have failed in clinical trials due to p53-induced feedback that enhances MDM2 expression. This underscores the urgent need to find an effective adaptive genotype or combination of targets.

Methods
Kinome-wide CRISPR/Cas9 knockout screen was performed to identify genes that modulate the response to MDM2 inhibitor using TP53 wild type cancer cells and found ULK1 as a candidate. The MTT cell viability assay, flow cytometry and LDH assay were conducted to evaluate the activation of pyroptosis and the synthetic lethality effects of combining ULK1 depletion with p53 activation. Dual-luciferase reporter assay and ChIP-qPCR were performed to confirm that p53 directly mediates the transcription of GSDME and to identify the binding region of p53 in the promoter of GSDME. ULK1 knockout / overexpression cells were constructed to investigate the functional role of ULK1 both in vitro and in vivo. The mechanism of ULK1 depletion to activate GSMDE was mainly investigated by qPCR, western blot and ELISA.

Results
By using high-throughput screening, we identified ULK1 as a synthetic lethal gene for the MDM2 inhibitor APG115. It was determined that deletion of ULK1 significantly increased the sensitivity, with cells undergoing typical pyroptosis. Mechanistically, p53 promote pyroptosis initiation by directly mediating GSDME transcription that induce basal-level pyroptosis. Moreover, ULK1 depletion reduces mitophagy, resulting in the accumulation of damaged mitochondria and subsequent increasing of reactive oxygen species (ROS). This in turn cleaves and activates GSDME via the NLRP3-Caspase inflammatory signaling axis. The molecular cascade makes ULK1 act as a crucial regulator of pyroptosis initiation mediated by p53 activation cells. Besides, mitophagy is enhanced in platinum-resistant tumors, and ULK1 depletion/p53 activation has a synergistic lethal effect on these tumors, inducing pyroptosis through GSDME directly.

Conclusion
Our research demonstrates that ULK1 deficiency can synergize with MDM2 inhibitors to induce pyroptosis. p53 plays a direct role in activating GSDME transcription, while ULK1 deficiency triggers upregulation of the ROS-NLRP3 signaling pathway, leading to GSDME cleavage and activation. These findings underscore the pivotal role of p53 in determining pyroptosis and provide new avenues for the clinical application of p53 restoration therapies, as well as suggesting potential combination strategies.
Host attraction and host feeding patterns indicate generalist feeding of Culex pipiens s.s. and Cx. torrentium
Authors: Wehmeyer Magdalena Laura , Jaworski Linda , Jöst Hanna , Șuleșco Tatiana , Rauhöft Leif , Afonso Sara M. Martins , Neumann Markus , Kliemke Konstantin , Lange Unchana , Kiel Ellen , Schmidt-Chanasit Jonas , Sauer Felix Gregor , Lühken Renke 
Published: August 2024

Abstract
Background
Mosquito host feeding patterns are an important factor of the species-specific vector capacity determining pathogen transmission routes. Culex pipiens s.s./Cx. torrentium are competent vectors of several arboviruses, such as West Nile virus and Usutu virus. However, studies on host feeding patterns rarely differentiate the morphologically indistinguishable females.

Methods
We analyzed the host feeding attraction of Cx. pipiens and Cx. torrentium in host-choice studies for bird, mouse, and a human lure. In addition, we summarized published and unpublished data on host feeding patterns of field-collected specimens from Germany, Iran, and Moldova from 2012 to 2022, genetically identified as Cx. pipiens biotype pipiens, Cx. pipiens biotype molestus, Cx. pipiens hybrid biotype pipiens × molestus, and Cx. torrentium, and finally put the data in context with similar data found in a systematic literature search.

Results
In the host-choice experiments, we did not find a significant attraction to bird, mouse, and human lure for Cx. pipiens pipiens and Cx. torrentium. Hosts of 992 field-collected specimens were identified for Germany, Iran, and Moldova, with the majority determined as Cx. pipiens pipiens, increasing the data available from studies known from the literature by two-thirds. All four Culex pipiens s.s./Cx. torrentium taxa had fed with significant proportions on birds, humans, and nonhuman mammals. Merged with the data from the literature from 23 different studies showing a high prevalence of blood meals from birds, more than 50% of the blood meals of Cx. pipiens s.s. were identified as birds, while up to 39% were human and nonhuman mammalian hosts. Culex torrentium fed half on birds and half on mammals. However, there were considerable geographical differences in the host feeding patterns.

Conclusions
In the light of these results, the clear characterization of the Cx. pipiens s.s./Cx. torrentium taxa as ornithophilic/-phagic or mammalophilic/-phagic needs to be reconsidered. Given their broad host ranges, all four Culex taxa could potentially serve as enzootic and bridge vectors.

Graphical Abstract
Efficacy of Qi-Gen powder for immunity enhancement and investigation of its therapeutic mechanisms through gene expression profiling
Authors: Gao Xueyan , Wang Pingping , Wang Shaolin , Yang Fenfang , Ma Danyang , Xu Xiaoqin , Huang Tingting , Xie Huisheng , Hao Zhihui 
Published: August 2024

AbstractInfection with different viruses threatens the health of animals in the livestock and poultry industry. Immunopotentiators can increase natural immunity and vaccination efficacy; however, most are expensive chemical and biological compounds with questionable safety. Traditional Chinese medicines (TCMs) such as Yupingfeng (YPF), a well-known immunomodulatory remedy, provide healthy alternatives to such agents. The aim of this study was to examine the therapeutic properties of Qi-Gen powder (QG) and compare them with those of YPF. The immune organ index, cytokine levels, and other indicators were utilized to evaluate the effects of QG in an immunosuppression mouse model. QG was further assessed for its ability to enhance vaccine effectiveness in chickens immunized for Newcastle disease virus (NDV). Potential therapeutic mechanisms and targets of QG were examined in the breast cancer cell line MCF-7 using microarray technology combined with the TCM systems pharmacology database of known targets. Compared with model controls, QG improved immunological function, outperforming YPF in mice. QG also enhanced the immunological response to NDV vaccine in immune organs and increased feed intake of chickens. Further research is needed to validate the link between the PI3K/Akt/GSK-3 pathway and the immune-boosting effects of QG.
When Your Friend is My Friend: How Loyalty Prompts Support for Indirect Ties in Moral Dilemmas
Authors: Berry Zachariah , Hildreth John Angus D. 
Published: August 2024

How are some criminals able to get away with wrongdoing for months or even years? Here, we consider the role of loyalty in facilitating networks of support for wrongdoers, examining whether the obligations of loyalty to direct ties (here, brokers) transfer through individuals’ social networks to their indirect ties, prompting them to support those indirect ties in moral dilemmas. Integrating research on brokering, loyalty, relational identity, and social norms, we propose that loyalty to a broker will prompt an individual to support an indirect tie accused of wrongdoing because loyalty activates one’s relational identity with the broker, which highlights the descriptive and relational injunctive norms associated with their role, leading them to view the broker’s request to support an indirect tie accused of wrongdoing as falling within the bounds of their loyalty-based obligations to the broker. Specifically, these norms reveal to the actor their benevolence-based trust in the broker, their value alignment with the broker, and relational concerns for not granting the broker’s request. We further demonstrate how a broker’s history of creating divisions between people moderates how the actor sees the broker and reduces their willingness to grant the request. Across 11 preregistered studies (n = 2,249)—10 experiments and a field study—we found support for our hypotheses: the obligations of loyalty to brokers did indeed transfer to indirect ties accused of wrongdoing, regardless of the type of wrongdoing or strength of evidence presented against the accused. Supplemental Material: The online appendix is available at https://doi.org/10.1287/orsc.2023.18003 .
THE CORRELATION BETWEEN HYPERTENSION AND COGNITIVE FUNCTION
Authors: Zuhir Elvina 
Published: August 2024

Background: Rapid increase in Indonesia health development lead to increase in life expectancy. This demographical shift implicated in altering disease pattern to dominate be degenerative diseases, such as hypertension. Hypertension affected morbidity and mortality rate significantly. Hypertension also known to correlated with increasing risk in cerebrovascular diseases that continue to cognitive function disorders such as vascular dementia.Â Objective: To know the relationship between hypertension and cognitive function.Methods: Using cross-sectional design with comparative study. Blood pressure measured by using sphygmomanometer and stethoscope, while cognitive function measured by using Mini Mental State Examination (MMSE) and Raven Progressive Matrices (RPM). This research was held in M. Djamil Hospital, Puskesmas Nanggalo Siteba, Puskesmas Padang Pasir, Puskesmas Alai, Puskesmas Andalas, Puskesmas Seberang Padang dan Puskesmas Pauh with consecutive sampling techniqueResult: There is no significant differentiation based on age and gender in hypertension and normotensive sample. There is significant differentiation in cognitive function in hypertension and norm tension sample (p-value< 0,05). Hypertension sample will have 7,8 times risk to had cognitive function disorders than normotensive sample (measured using MMSE; OR: 7,8). Hypertension sample will have 3,3Â times risk to had cognitive function disorders than normotensive sample (measured using RPM; OR: 3,3).Conclusion: There is significant differentiation in cognitive function in hypertension and normotensive sample. Hypertension subject will have 3,3 to 7,8 times risk to had cognitive function disorders than normotensive
Hubungan Kepemimpinan dan Komunikasi dengan Kinerja Tenaga Kesehatan di Seluruh Puskesmas Kota Yogyakarta
Authors: Amalia Maya , Mudayana Ahmad Ahid 
Published: August 2024

One of the government's efforts to achieve health development goals is the issuance of the Minister of Health regulation of the Republic of Indonesia Number 75 year 2014 about Community Health Center (Puskesmas).Good leadership and communication are needed for the achievement of organizational goals. Implementation of community health center policies that are less than optimal can be characterized by lack of communication, programs that haven't been socialized and weak human resources in providing services. This can occur because the employees not fulfill their duties and responsibilities. So evaluation is needed to produce good performance. The purpose of this study is to find out the relationship between leadership and communication with the performance of health workers in all over the community health centers in Yogyakarta City. This research is analytic research with cross-sectional approach. There are 189 community health centers employees as the samples of this study who were selected by propotionate stratified random sampling. This study conducted in April - June 2019 in all over community health center in Yogyakarta city. The data were analyzed using univariate and bivariate analysis with chi square statistical test.
The chi square statistical test show that the p-value of leadership with performance is 0,012 (p-value <0,05), as well as the statistical test performed on communication variables with performance show that the p-value is 0,011 (p-value <0,05). There is a significant relationship between leadership and communication with performance.
Evaluasi Kegiatan Surveilans dalam Pencegahan dan Pengendalian Infeksi di RSUD KRT. Setjonegoro Wonosobo
Authors: Primadani Mahardika , Hastuti Siti Kurnia Widi 
Published: August 2024

Nosocomial infections or currently known as Health care associated infections (HAIs) is an important problem worldwide and an interesting issue to research, especially regarding infection prevention efforts. The prevalence of HAIs in world hospitals reaches 9% or approximately 1.40 million. From the surveillance data of Setjonegoro Hospital from 2018 to 2020, it was found that the incidence of phlebitis was 7.2 ‰. One of the strategies to control HAIs is surveillance. The purpose of this study was to evaluate the implementation of the surveillance program in the Prevention and Control of Infection at RSUD Setjonegoro, Wonosobo Regency. This type of research is a qualitative study with a phenomenological design. The research subjects were the chair of the PPI, IPCN, IPCLN and IPCD committees. The instruments used were observation and interview guidelines. The data analysis technique used the theory of Miles and Huberman. Surveillance activity in RSUD KRT. Setjonegoro Wonosobo is quite optimal, both in terms of human resources, facilities, and infrastructure to the timeliness of reporting, so that the surveillance reports always get feedback to find out what follow-up plans will be carried out. The mistake that often occurs is the negligence of officers in inputting surveillance data. The surveillance activities at the Setjonegoro Regional Hospital have been running well, all PPI Teams have received training related to surveillance activities, data input is carried out using software, reporting of surveillance results is running on time, and feedback is given both verbally and in writing.
Research Progress on Patients of Esophageal Cancer Complicated with Sarcopenia
Authors: Fu PingPing , Xiao XiaoFang 
Published: August 2024

Aims/Background The application of immunochemotherapy has significantly enhanced the quality of life and overall survival of patients with esophageal cancer. Sarcopenia, which is increasingly prevalent in these patients, markedly affects prognosis, but can be reversed by appropriate and effective treatment. Methods The narrative review was conducted on PubMed using the keywords (“esophageal” or “esophagus” and “sarcopenia”). Results This article reviews the measurement, timing, and intervention strategies for sarcopenia in patients with esophageal cancer. It summarizes the evaluation indicators of skeletal muscle loss in these patients, analyzes the barriers to intervention for frailty among esophageal cancer patients, and proposes corresponding countermeasures. Conclusion Patients with esophageal cancer often suffer from severe sarcopenia. Clinical intervention is crucial in addressing this issue.
Constructing a Nomogram for Predicting Pelvic Osteosarcoma: A Retrospective Study Based on the SEER Database and a Chinese Cohort
Authors: Xu Yefeng , Yan Qingying , Yang Jiewen , Cheng Miao , Chen Jialu , Yao Yongwei , Liu Yunxia 
Published: August 2024

Aims/Background Generally, pelvic osteosarcoma has a worse prognosis compared with limb osteosarcoma. This study aims to create and validate a new nomogram for predicting the prognosis of pelvic osteosarcoma. Methods Clinical data of 62 patients derived from the Surveillance, Epidemiology, and End Results (SEER) database and 31 Chinese patients diagnosed with pelvic osteosarcoma were gathered. Kaplan-Meier survival analysis was utilized to calculate the median survival time for all variables. Univariate and multivariate Cox regression models were employed to identify the prognostic factors of pelvic osteosarcoma. A nomogram was constructed using data gleaned from the SEER cohort and verified using the receiver operating characteristic (ROC) curve and calibration plot in the Chinese cohort. Results Kaplan-Meier analysis revealed that individuals of other races (Asians) (hazard ratio (HR) = 0.24, 95% confidence interval (CI): 0.1–0.57, p = 0.001), aged ≤51 years old (HR = 0.4, 95% CI: 0.22–0.73, p = 0.003), and with tumor size ≤160 mm (HR = 0.37, 95% CI: 0.2–0.71, p = 0.03) had better survival outcomes. Conversely, factors such as no primary surgery (HR = 3.6, 95% CI: 1.81–7.15, p < 0.001), lung metastasis (HR = 1.96, 95% CI: 1.17–3.28, p = 0.010), and radiotherapy (HR = 1.89, 95% CI: 1.10–3.25, p = 0.021) were associated with poorer survival. Multivariate Cox analysis indicated that lung metastasis (HR = 2.57, 95% CI: 1.29–5.13, p = 0.008), other races (Asians) (HR = 0.23, 95% CI: 0.07–0.75, p = 0.015), tumor size (HR = 0.28, 95% CI: 0.13–0.62, p = 0.001) and age (HR = 0.3, 95% CI: 0.16–0.59, p < 0.001) were independent prognostic factors for pelvic osteosarcoma. Univariate and multivariate Cox regression models identified three independent variables in the training cohort: age, lung metastasis, and tumor size. A predictive nomogram was developed based on the data from the SEER cohort and validated in the Chinese cohort. The areas under the curves (AUCs) that are used to predict 1-year, 2-year, and 3-year survival rates were 0.81 (95% CI: 0.68–0.94), 0.75 (95% CI: 0.63–0.86), and 0.80 (95% CI: 0.70–0.89) in the training cohort, and 0.67 (95% CI: 0.30–1.04), 0.66 (95% CI: 0.43–0.90) and 0.71 (95% CI: 0.50–0.93) in the validation cohort. Conclusion The predictive nomogram constructed in this study facilitates accurate and effective prediction of the overall survival of patients with pelvic osteosarcoma and helps enhance the clinical decision-making process.
Navigated ultrasound bronchoscopy with integrated positron emission tomography—A human feasibility study
Authors: Kildahl-Andersen Arne , Hofstad Erlend Fagertun , Solberg Ole-Vegard , Sorger Hanne , Amundsen Tore , Langø Thomas , Leira Håkon Olav 
Published: August 2024

Background and objective
Patients suspected to have lung cancer, undergo endobronchial ultrasound bronchoscopy (EBUS) for the purpose of diagnosis and staging. For presumptive curable patients, the EBUS bronchoscopy is planned based on images and data from computed tomography (CT) images and positron emission tomography (PET). Our study aimed to evaluate the feasibility of a multimodal electromagnetic navigation platform for EBUS bronchoscopy, integrating ultrasound and segmented CT, and PET scan imaging data.

Methods
The proof-of-concept study included patients with suspected lung cancer and pathological mediastinal/hilar lymph nodes identified on both CT and PET scans. Images obtained from these two modalities were segmented to delineate target lymph nodes and then incorporated into the CustusX navigation platform. The EBUS bronchoscope was equipped with a sensor, calibrated, and affixed to a 3D printed click-on device positioned at the bronchoscope’s tip. Navigation accuracy was measured postoperatively using ultrasound recordings.

Results
The study enrolled three patients, all presenting with suspected mediastinal lymph node metastasis (N1-3). All PET-positive lymph nodes were displayed in the navigation platform during the EBUS procedures. In total, five distinct lymph nodes were sampled, yielding malignant cells from three nodes and lymphocytes from the remaining two. The median accuracy of the navigation system was 7.7 mm.

Conclusion
Our study introduces a feasible multimodal electromagnetic navigation platform that combines intraoperative ultrasound with preoperative segmented CT and PET imaging data for EBUS lymph node staging examinations. This innovative approach holds promise for enhancing the accuracy and effectiveness of EBUS procedures.
Causal association of menstrual reproductive factors on the risk of osteoarthritis: A univariate and multivariate Mendelian randomization study
Authors: Tan Xinzhe , Mei Yifang , Zhou Yihao , Liao Zhichao , Zhang Pengqi , Liu Yichang , Han Yixiao , Wang Dongyan 
Published: August 2024

Objective
Several observational studies have revealed a potential relationship between menstrual reproductive factors (MRF) and osteoarthritis (OA). However, the precise causal relationship remains elusive. This study performed Mendelian randomization (MR) to provide deeper insights into this relationship.

Methods
Utilizing summary statistics of genome-wide association studies (GWAS), we conducted univariate MR to estimate 2 menstrual factors (Age at menarche, AAM; Age at menopause, AMP) and 5 reproductive factors (Age at first live birth, AFB; Age at last live birth, ALB; Number of live births, NLB; Age first had sexual intercourse, AFSI; Age started oral contraceptive pill, ASOC) on OA (overall OA, OOA; knee OA, KOA and hip OA, HOA). The sample size of MRF ranged from 123846 to 406457, and the OA sample size range from 393873 to 484598. Inverse variance weighted (IVW) method was used as the primary MR analysis methods, and MR Egger, weighted median was performed as supplements. Sensitivity analysis was employed to test for heterogeneity and horizontal pleiotropy. Finally, multivariable MR was utilized to adjust for the influence of BMI on OA.

Results
After conducting multiple tests (P<0.0023) and adjusting for BMI, MR analysis indicated that a lower AFB will increase the risk of OOA (odds ratio [OR] = 0.97, 95% confidence interval [CI]: 0.95–0.99, P = 3.39×10−4) and KOA (OR = 0.60, 95% CI: 0.47–0.78, P = 1.07×10−4). ALB (OR = 0.61, 95% CI: 0.45–0.84, P = 2.06×10−3) and Age AFSI (OR = 0.66, 95% CI: 0.53–0.82, P = 2.42×10−4) were negatively associated with KOA. In addition, our results showed that earlier AMP adversely affected HOA (OR = 1.12, 95% CI: 1.01–1.23, P = 0.033), and earlier ASOC promote the development of OOA (OR = 0.97, 95% CI: 0.95–1.00, P = 0.032) and KOA (OR = 0.58, 95% CI: 0.40–0.84, P = 4.49×10−3). ALB (OR = 0.98, 95% CI: 0.96–1.00, P = 0.030) and AFSI (OR = 0.98, 95% CI: 0.97–0.99, P = 2.66×10−3) also showed a negative association with OOA but they all did not pass multiple tests. The effects of AAM and NLB on OA were insignificant after BMI correction.

Conclusion
This research Certificates that Early AFB promotes the development of OOA, meanwhile early AFB, ALB, and AFSI are also risk factors of KOA. Reproductive factors, especially those related to birth, may have the greatest impact on KOA. It provides guidance for promoting women’s appropriate age fertility and strengthening perinatal care.