bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of genomic instability related lncRNA signature with prognostic value and its role in cancer immunotherapy in pancreatic cancer
Authors: Zhu Xiaole , Yu Rong , Peng Yunpeng , Miao Yi , Jiang Kuirong , Li Qiang 
Published: September 2022

Background: Increasing evidence suggested the critical roles of lncRNAs in the maintenance of genomic stability. However, the identification of genomic instability-related lncRNA signature (GILncSig) and its role in pancreatic cancer (PC) remains largely unexplored.Methods: In the present study, a systematic analysis of lncRNA expression profiles and somatic mutation profiles was performed in PC patients from The Cancer Genome Atlas (TCGA). We then develop a risk score model to describe the characteristics of the model and verify its prediction accuracy. ESTIMATE algorithm, single-sample gene set enrichment analysis (ssGSEA), and CIBERSORT analysis were employed to reveal the correlation between tumor immune microenvironment, immune infiltration, immune checkpoint blockade (ICB) therapy, and GILncSig in PC.Results: We identified 206 GILnc, of which five were screened to develop a prognostic GInLncSig model. Multivariate Cox regression analysis and stratified analysis revealed that the prognostic value of the GILncSig was independent of other clinical variables. Receiver operating characteristic (ROC) analysis suggested that GILncSig is better than the existing lncRNA-related signatures in predicting survival. Additionally, the prognostic performance of the GILncSig was also found to be favorable in patients carrying wild-type KRAS, TP53, and SMAD4. Besides, a nomogram exhibited appreciable reliability for clinical application in predicting the prognosis of patients. Finally, the relationship between the GInLncSig model and the immune landscape in PC reflected its application value in clinical immunotherapy.Conclusion: In summary, the GILncSig identified by us may serve as novel prognostic biomarkers, and could have a crucial role in immunotherapy decisions for PC patients.
Case report: The MSI-L/p-MMR metastatic rectal cancer patient who failed systemic therapy responds to anti-PD-1 immunotherapy after stereotactic body radiation-therapy
Authors: Liu Shijin , Zhang Yiran , Lin Yujian , Wang Peize , Pan Yunlong 
Published: September 2022

BackgroundTraditionally, patients with microsatellite stability (MSS)/microsatellite instability-Low (MSI-L)/proficient mismatch repair (p-MMR) metastatic colorectal cancer (mCRC) have had poor benefit from immunotherapy. Therefore, how to enhance the response of immunotherapy is still a challenge for MSS/MSI-L/p-MMR CRC patient.Case presentationWe report a special case of a rectal cancer patient with programmed death-ligand 1 (PD-L1) negative expression, MSI-L/p-MMR, tumor mutational burden-low (TMB-L) and liver metastases, who partial response (PR) to immunotherapy after systemic therapy failure including chemotherapy, anti-angiogenesis therapy and stereotactic body radiation-therapy (SBRT). The computed tomography (CT) results showed that among three liver metastases had been reduction or disappearance after Tislelizumab treatment for three times. Besides, the carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA199) decrease and maintained at a low level for 3 months. The progression-free survival (PFS) of patient has exceeded 3 months.ConclusionsThis case indicates that the patient with MSI-L/p-MMR mCRC can respond to anti-PD-1 immunotherapy after systemic therapy. And the SBRT (targeting liver metastases) may a method for increase-sensitivity of immunotherapy in CRC patients with MSI-L/p-MMR.
Electrical impedance tomography to aid in the identification of hypoxemia etiology: Massive atelectasis or pneumothorax? A case report
Authors: Zhou Runshi , He Chaokai , Chi Yi , Yuan Siyi , Tang Bo , Li Zunzhu , Li Qi , He Huaiwu , Long Yun 
Published: September 2022

BackgroundBedside ultrasound is often used to determine the etiology of hypoxaemia, but not always with definitive results. This case reports the application of electrical impedance tomography (EIT) and saline injection to determine the etiology of hypoxaemia in a complex case that could not be identified by bedside ultrasound. The determination of the etiology of hypoxaemia by EIT and saline injection, regional ventilation and perfusion information can be used as a new clinical diagnostic method.Case presentationA post-cardiac surgery patient under prolonged mechanical ventilation for lung emphysema developed sudden hypoxemia in the intensive care unit (ICU). A line pattern and lung sliding sign abolishment were found in the left lung, but there was no evidence of a lung point sign on bedside ultrasound. Hence, the initial diagnosis was considered to be a massive pneumothorax. To further define the etiology, EIT and saline bolus were used to assess regional ventilation and perfusion. A massive ventilation defect was found in the left lung, in which regional perfusion was maintained, resulting in an intrapulmonary shunt in the left lung. Finally, the conjecture of a pneumothorax was ruled out considering the massive atelectasis. After the diagnosis was clarified, hypoxaemia was corrected by restorative ventilation of the left lung after changing the patient's posture and enhancing sputum drainage with chest physiotherapy.ConclusionsThis was the clinical case involving EIT and saline bolus to establish the differential diagnosis and guide clinical decisions for patients with acute hypoxemia. This study highlighted that combination regional ventilation, EIT perfusion, and saline bolus provided helpful information for determining the etiology of hypoxemia. The results of this study contribute to the development of emergency patient management.
Eight gene mutation-based polygenic hazard score as a potential predictor for immune checkpoint inhibitor therapy outcome in metastatic melanoma
Authors: Zhao Liqin , Luo Ting , Jiang Jinling , Wu Junwei , Zhang Xiaowei 
Published: September 2022

Background: Immune checkpoint inhibitor (ICI) therapies have revolutionized the treatment of metastatic cutaneous melanoma, but have only benefitted a subset of them. Gene mutations were reported to impact the ICI therapy outcomes in metastatic melanoma but have not been fully investigated. Hence, we systematically analyzed the impact of cancer-related gene mutations on the clinical outcome in metastatic melanoma patients who underwent ICI therapies.Methods: Publicly available discovery and validation cohorts (312 patients and 110 patients respectively, all the patients received ICI therapies) were included in this study. Cox proportional hazards regression analysis was used to assess the association of 468 cancer-related gene mutations with overall survival (OS) in the discovery cohort, and the polygenic hazard score (PHS) was constructed subsequently, and validated in the validation cohort. The Tumor Immune Estimation Resource (TIMER) online tools, which are based on The Cancer Genome Atlas database, were used to analyze the impact of gene mutations on tumor-infiltrated immune cells in melanoma samples.Results: We found eight gene mutations that were significantly associated with the overall survival (BAP1, CARD11, IGF1R, KMT2D, PTPRD, PTPRT, ROS1, and TERT, p &lt; 0.05, mutation frequency &gt;0.05). The PHS, which was based on these genes, was found to effectively discriminate the subset which benefited most from ICI therapies (HR = 1·54, 95%CI, 1.25–1.95; p &lt; 0.001). After adjusting with age, sex, ICI regimes, and tumor mutation burden (TMB), we found that PHS was an independent predictor for the outcome of ICI therapies (adjusted HR = 1.84, 95%CI, 1.22–2.79; p = 0.004). The PHS was validated in the validation cohort (log-Rank p = 0.038). Further research found that CARD11 and PTPRD mutations were significantly associated with more tumor-infiltrated immune cells in melanoma samples.Conclusion: For the first time, we have shown that PHS can independently and effectively predict the ICI therapy outcome in metastatic melanoma, which once validated by larger research, may help the decision-making process in melanoma.
Emerging therapies for autosomal dominant polycystic kidney disease with a focus on cAMP signaling
Authors: Zhou Xia , Torres Vicente E. 
Published: September 2022

Autosomal dominant polycystic kidney disease (ADPKD), with an estimated genetic prevalence between 1:400 and 1:1,000 individuals, is the third most common cause of end stage kidney disease after diabetes mellitus and hypertension. Over the last 3 decades there has been great progress in understanding its pathogenesis. This allows the stratification of therapeutic targets into four levels, gene mutation and polycystin disruption, proximal mechanisms directly caused by disruption of polycystin function, downstream regulatory and signaling pathways, and non-specific pathophysiologic processes shared by many other diseases. Dysfunction of the polycystins, encoded by the PKD genes, is closely associated with disruption of calcium and upregulation of cyclic AMP and protein kinase A (PKA) signaling, affecting most downstream regulatory, signaling, and pathophysiologic pathways altered in this disease. Interventions acting on G protein coupled receptors to inhibit of 3′,5′-cyclic adenosine monophosphate (cAMP) production have been effective in preclinical trials and have led to the first approved treatment for ADPKD. However, completely blocking cAMP mediated PKA activation is not feasible and PKA activation independently from cAMP can also occur in ADPKD. Therefore, targeting the cAMP/PKA/CREB pathway beyond cAMP production makes sense. Redundancy of mechanisms, numerous positive and negative feedback loops, and possibly counteracting effects may limit the effectiveness of targeting downstream pathways. Nevertheless, interventions targeting important regulatory, signaling and pathophysiologic pathways downstream from cAMP/PKA activation may provide additive or synergistic value and build on a strategy that has already had success. The purpose of this manuscript is to review the role of cAMP and PKA signaling and their multiple downstream pathways as potential targets for emergent therapies for ADPKD.
Changes in dietary intake, chronotype and sleep pattern upon Ramadan among healthy adults in Jeddah, Saudi Arabia: A prospective study
Authors: Alzhrani Ameera , Alhussain Maha H. , BaHammam Ahmed S. 
Published: September 2022

BackgroundNotable lifestyle changes can occur in Ramadan due to the sudden shift in eating routine with fasting during daylight hours. This study aimed to examine the changes in dietary intakes, chronotype, sleep pattern, and physical activity level before and during Ramadan in healthy adults.MethodsThis study was conducted in Jeddah city, Saudi Arabia, and convenience sampling was used. To compare dietary, chronotype and sleep pattern changes before and during Ramadan, data were collected in two separate periods: the first period was 2 months before Ramadan, and the second period was during the last 3 weeks of Ramadan. Dietary intake was assessed using 24-h food recall and chronotype using Morningness-Eveningness Questionnaire. Daytime sleepiness and sleep duration were assessed using the Epworth sleepiness scale and a sleep diary for seven consecutive days, respectively. Anthropometric measurements were also taken across the study periods.ResultsA total of 115 adults (96 females and 19 males) were included in the study. Significant increases in daily calorie and carbohydrate intakes during Ramadan than before Ramadan were noted (calorie intake: 1,482.9 ± 536.4 kcal/day before Ramdan vs. 1,635.5 ± 635.1 kcal/day during Ramadan; carbohydrate intake: 180.8 ± 72.1 g/day before Ramadan vs. 202.6 ± 88.7 g/day during Ramadan; p &lt; 0.05). Chronotypes and daytime sleepiness were also associated significantly with Ramadan fasting. A significant slight reduction in body weight during Ramadan was observed (66.4 ± 18.1 kg before Ramdan vs. 66.1 ± 17.8 kg before Ramadan and during Ramadan, respectively; p &lt; 0.05).ConclusionThis study indicates that Ramadan diurnal fasting was associated with greater calorie and carbohydrate intake, changes in chronotype, and daytime sleepiness. The study also suggests that Ramadan diurnal fasting model may be a promising weight loss strategy.
Soy consumption and serum uric acid levels: A systematic review and meta-analysis
Authors: Duan Ying , Qi Qi , Liu Zihao , Zhang Min , Liu Huaqing 
Published: September 2022

BackgroundSoy consumption has health benefits, but the relationship between soy and uric acid remains uncertain. This meta-analysis and systematic review evaluated the effects of soy intake on plasma uric acid.MethodsPubMed, Embase, CNKI, and the Cochrane Library were searched for studies evaluating the effects of soy, soy products, soy protein, and soy isoflavones on uric acid levels. The primary outcome was serum or plasma uric acid concentration. Study quality was evaluated by the Cochrane Collaboration and SYRCLE risk-of-bias tools.ResultsA total of 17 studies were included. Qualitative analysis of three human clinical studies of acute effects revealed that soy consumption increased serum uric acid concentration; however, soy-derived products, including tofu, bean curd cake, and dried bean curd sticks, had no significant effect on serum uric acid. A meta-analysis of five long-term human studies (10 data sets) revealed that soy protein and soy isoflavones had no significant effects on uric acid levels [weighted mean difference (WMD) = –2.11; 95% confidence interval (CI): –8.78, 4.55; p = 0.53]. However, most epidemiological data revealed that soy intake is inversely associated with uric acid levels. Meta-analysis of nine animal trials (29 data sets) revealed that soy protein and soy isoflavones significantly reduced serum uric acid concentrations (vs. controls; MD = –38.02; 95% CI: –50.60, –25.44; p &lt; 0.001).ConclusionSoy and its products have different effects on serum uric acid. Soy products like tofu, bean curd cake, and dried bean curd sticks could be high-quality protein sources for individuals with hyperuricemia or gout. It can be beneficial to nutritionists and healthcare decision-makers reconsider their conceptions about the relationship between soy and uric acid levels according to the latest and further scientific study results.Systematic review registration[www.crd.york.ac.uk/PROSPERO], identifier [CRD42022331855].
The impact of body composition and fat distribution on blood pressure in young and middle-aged adults
Authors: Zhao Song , Tang Jiamin , Zhao Yifan , Xu Chong , Xu Yawei , Yu Shikai , Zhang Yi 
Published: September 2022

BackgroundThe relative contributions of each component of body composition to blood pressure (BP) remain unclear.ObjectiveWe aimed to comprehensively investigate the impact of body composition and fat distribution on BP and quantify their relative contributions to BP in a large cohort with young and middle-aged adults.Methods14,412 participants with available data on whole-body DXA measurement from the National Health and Nutrition Examination Survey were included. Multiple stepwise linear regressions of BP on components of body composition and fat distribution were built. Then, relative importance analysis was performed to quantify the contributions of each component to BP.ResultsThe median age of participants was 36 years and there were 50.7% women. Linear regression with mutual adjustment showed that total fat mass, total muscle mass, and trunk fat mass significantly and positively associated with BP; however, arm and leg fat mass significantly and negatively associated with BP. In men, after further adjusted for potential covariates, SBP were significantly determined by trunk fat mass (β = 0.33, P &lt; 0.001), leg fat mass (β = − 0.12, P &lt; 0.001), and total muscle mass (β = 0.10, P &lt; 0.001); and DBP were significantly determined by trunk fat mass (β = 0.52, P &lt; 0.001), leg fat mass (β = −0.15, P &lt; 0.001), arm fat mass (β = −0.23, P &lt; 0.001), and total muscle mass (β = 0.06, P &lt; 0.001). Similar results were observed in women. Relative importance analysis showed that trunk fat mass was the major contributor (38–61%) to both SBP and DBP; meanwhile, total muscle mass also made relatively great contribution (35–43%) to SBP.ConclusionBoth fat mass and muscle mass independently associated with and substantially contributed to SBP in both men and women. After full adjustment, trunk fat mass positively associated with both SBP and DBP, and was the most dominant contributor to BP; however, leg fat mass negatively associated with both SBP and DBP.
Platinum resistant recurrence and early recurrence in a multi-centre cohort of patients undergoing interval cytoreductive surgery for advanced epithelial ovarian cancer
Authors: Bhatt Aditi , Sinukumar Snita , Kepenekian Vahan , Kammar Praveen , Mehta Sanket , Shaikh Sakina , Gertych Witold , Bakrin Naoual , Glehen Olivier 
Published: September 2022

BackgroundAggressive locoregional therapies like hyperthemic intraperitoneal chemotherapy(HIPEC) and total parietal peritonectomy(TPP) have been used to delay recurrence in patients with advanced ovarian cancer undergoing interval cytoreductive surgery(CRS). The aim of this retrospective study was to evaluate the incidence of platinum resistant recurrence (PRR) and early recurrence (ER)(recurrence within 6 months and 1 year of the last dose of platinum based therapy, respectively) in patients undergoing interval CRS. The secondary goal was to study impact of each of these therapies on PRR and ER.MethodsOne-hundred and fifty-three patients undergoing interval CRS from July 2018 to June 2020 were included. The surgical strategy was to perform a TPP in which the entire parietal peritoneum is resected irrespective of the disease extent or a selective parietal peritonectomy (SPP) in which only the peritoneum bearing visible residual disease is resected. The use of HIPEC was at the discretion of the treating oncologists.ResultsThe median surgical PCI was 15 [range, 0-37]. A CC-0 resection was obtained in 119 (77.7%) and CC-1 in 29 (18.9%) patients. Eighty-one (53%) patients had a TPP and 72 (47%) had SPP. HIPEC was performed in 98(64%) patients. Bevacizumab maintenance was administered to 31(19.6%) patients. No patients received PARP inhibitors during first-line therapy. PRR was observed in 8(5.2%) patients and ER in 30(19.6%). The respective incidences of PRR and ER were 4.9% and 16% in the TPP group, 4.1% and 23.6% in the SPP group, 9% and 20% in the no-HIPEC group and 3% and 19.3% in the HIPEC groups. On multivariate analysis, CC-0(p=0.014) resection and HIPEC(p=0.030) were independent predictors of a low ER. All patients with PR and 70% with ER had peritoneal recurrence with or without extra-peritoneal sites of recurrence.ConclusionsThe incidence of PRR and ER in this cohort was low as compared to historical data. This low incidence could be attributed to the use of aggressive locoregional therapies like TPP and HIPEC. In future, studies should be conducted to confirm these findings and evaluate the potential additive benefit of TPP and HIPEC coupled together as well as their combination with maintenance therapies.
Potentially functional variants of MAP3K14 in the NF-κB signaling pathway genes predict survival of HBV-related hepatocellular carcinoma patients
Authors: Huang Qiongguang , Liu Yingchun , Qiu Moqin , Lin Qiuling , Wei Xueyan , Zhou Zihan , Liang Xiumei , Li Runwei , Chen Weiyi , Zhou Xianguo , Yu Hongping 
Published: September 2022

BackgroundThe NF-κB signaling pathway plays an important role in associating inflammation with tumor development and progression. However, few studies have reported that roles of genetic variants of the NF-κB signaling pathway genes in survival of patients with HBV-related hepatocellular carcinoma (HBV-HCC), especially with regards to potentially functional SNPs.MethodsWe used multivariate Cox proportional hazards regression to evaluate associations between 2,060 single nucleotide polymorphisms (SNPs) in 20 NF-κB signaling pathway genes and survival of 866 HBV-HCC patients, which were randomly split (1:1) into discovery and validation datasets. Expression quantitative trait loci (eQTL) analysis was conducted to identify associations between survival-associated SNPs and mRNA expression of corresponding genes. Furthermore, online database was used to assess mRNA expression of corresponding genes and survival. Finally, receiver operating characteristic (ROC) curves were used to assess the prediction accuracy of models integrating both clinical and genetic variables on HCC survival.ResultsA total of 6 SNPs in MAP3K14 remained significantly associated with OS of HBV-HCC patients (P&lt;0.05, BFDP&lt;0.8). Further eQTL analysis demonstrated that significant correlations between the rs2074292 (G&gt;A) A allele was associated with higher mRNA expression levels of MAP3K14 (P=0.044) in normal liver tissue, which was associated with worse survival of HBV-HCC patients. In the additive model, after adjusting for age, sex, smoking status, drinking status, AFP level, cirrhosis, embolus and BCLC stage, the combined dataset showed that HBV-HCC patients carrying the rs2074292 AA and GA genotypes (HR=1.71, 95%CI= 1.29-2.27, P=0.000) (HR=1.40, 95%CI=1.10-1.77, P=0.005) have worse OS than GG genotype, respectively. The addition of risk genotypes to the prediction models increased the AUC significantly from 71.15% to 73.11% (P=0.012) and from 72.55% to 74.21% (P=0.010) for 1-year and 3-year OS, respectively.ConclusionOur study indicated that MAP3K14 rs2074292 A allele may be a potential predictor of HBV-HCC survival, likely regulating MAP3K14 mRNA expression.