bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic significance of EGFR, AREG and EREG amplification and gene expression in muscle invasive bladder cancer
Authors: Uysal Daniel , Thaqi Blerta , Fierek Alexander , Jurgowski David , Popovic Zoran V. , Siegel Fabian , Michel Maurice Stephan , Nuhn Philipp , Worst Thomas Stefan , Erben Philipp , Nitschke Katja 
Published: May 2024

IntroductionMuscle invasive bladder cancer (MIBC) remains a prevalent cancer with limited therapeutic options, obviating the need for innovative therapies. The epidermal growth factor receptor (EGFR) is a linchpin in tumor progression and presents a potential therapeutic target in MIBC. Additionally, the EGFR ligands AREG and EREG have shown associations with response to anti-EGFR therapy and improved progression-free survival in colorectal carcinoma.Materials and methodsWe investigated the prognostic significance of EGFR, AREG, and EREG in MIBC. Gene expression and copy number analyses were performed via qRT-PCR on tissue samples from 100 patients with MIBC who underwent radical cystectomy at the University Hospital Mannheim (MA; median age 72, interquartile range [IQR] 64–78 years, 25% female). Results were validated in 361 patients from the 2017 TCGA MIBC cohort (median age 69, IQR 60–77 years, 27% female), in the Chungbuk and MDACC cohort. Gene expressions were correlated with clinicopathologic parameters using the Mann-Whitney test, Kruskal-Wallis- test and Spearman correlation. For overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) gene expression was analyzed with Kaplan-Meier and Cox-proportional hazard models.ResultsSignificant gene expression differences in EGFR, AREG, and EREG could be detected in all cohorts. In the TCGA cohort, EGFR expression was significantly elevated in patients with EGFR amplification and KRAS wildtype. High AREG expression independently predicted longer OS (HR = 0.35, CI 0.19 - 0.63, p = 0.0004) and CSS (HR = 0.42, CI 0.18 – 0.95, p = 0.0378) in the MA cohort. In the TCGA cohort, high EGFR, AREG, and EREG expression correlated with shorter OS (AREG: HR = 1.57, CI 1.12 – 2.20, p = 0.0090) and DFS (EGFR: HR = 1.91, CI 1.31 – 2.8, p = 0.0008). EGFR amplification was also associated with reduced DFS.DiscussionHigh EGFR and EREG indicate worse survival in patients with MIBC. The prognostic role of AREG should further be investigated in large, prospective series. Divergent survival outcomes between the four cohorts should be interpreted cautiously, considering differences in analysis methods and demographics. Further in vitro investigations are necessary to elucidate the functional mechanisms underlying the associations observed in this study.
Three-year follow-up study reveals improved survival rate in NSCLC patients underwent guideline-concordant diagnosis and treatment
Authors: Mu Huijuan , Yang Xing , Li Yanxia , Zhou Bingzheng , Liu Li , Zhang Minmin , Wang Qihao , Chen Qian , Yan Lingjun , Sun Wei , Pan Guowei 
Published: May 2024

BackgroundNo studies in China have assessed the guideline-concordance level of the first-course of non-small cell lung cancer (NSCLC) diagnosis and treatment and its relationship with survival. This study comprehensively assesses the current status of guideline-concordant diagnosis (GCD) and guideline-concordant treatment (GCT) of NSCLC in China and explores its impact on survival.MethodsFirst course diagnosis and treatment data for NSCLC patients in Liaoning, China in 2017 and 2018 (n=1828) were used and classified by whether they underwent GCD and GCT according to Chinese Society of Clinical Oncology (CSCO) guidelines. Pearson’s chi-squared test was used to determine unadjusted associations between categorical variables of interest. Logistic models were constructed to identify variables associated with GCD and GCT. Kaplan–Meier analysis and log-rank tests were used to estimate and compare 3-year survival rates. Multivariate Cox proportional risk models were constructed to assess the risk of cancer mortality associated with guideline-concordant diagnosis and treatment.ResultsOf the 1828 patients we studied, 48.1% underwent GCD, and 70.1% underwent GCT. The proportions of patients who underwent both GCD and GCT, GCD alone, GCT alone and neither GCD nor GCT were 36.7%, 11.4%, 33.5% and 18.4%, respectively. Patients in advanced stage and non-oncology hospitals were significantly less likely to undergo GCD and GCT. Compared with those who underwent neither GCD nor GCT, patients who underwent both GCD and GCT, GCD alone and GCT alone had 35.2%, 26.7% and 35.7% higher 3-year survival rates; the adjusted lung cancer mortality risk significantly decreased by 29% (adjusted hazard ratio[aHR], 0.71; 95% CI, 0.53–0.95), 29% (aHR, 0.71; 95% CI, 0.50–1.00) and 32% (aHR, 0.68; 95% CI, 0.51–0.90).ConclusionThe 3-year risk of death is expected to be reduced by 29% if patients with NSCLC undergo both GCD and GCT. There is a need to establish an oncology diagnosis and treatment data management platform in China to monitor, evaluate, and promote the use of clinical practice guidelines in healthcare settings.
Unexpected decrease in necrotizing enterocolitis morbidity during the COVID-19 pandemic-A single-centre retrospective study
Authors: Wang Yu , Cui Mingling , Li Lili , Gao Chuchu , Feng Zongtai , Cai Yan , Yang Zuming , Shen Lirong 
Published: May 2024

BackgroundThe impact of the coronavirus disease 2019 (COVID-19) pandemic on neonatal necrotizing enterocolitis (NEC) is not well characterised. This cross-sectional study evaluated the potential effects of pandemic-related measures on NEC morbidity in premature infants in a neonatal ward during the COVID-19 pandemic.MethodsThis was a retrospective study conducted in a tertiary neonatal ward in eastern and central China over 6 consecutive years (2017, 2018, 2019, 2020, 2021 and 2022). The medical records of 189 premature infants with stage II or III NEC were reviewed for clinical manifestations and aetiologies. The data were analysed and compared between the prepandemic period (2017, 2018, and 2019) and the pandemic period (2020, 2021 and 2022).ResultsA total of 9,903 infants with gestational age (GA) &lt; 37 weeks were enrolled, including 5,382 in the prepandemic period and 4,521 in the pandemic period. A reduction in stage II or III NEC morbidity was observed in infants with GA &lt; 37 weeks, with an average annual morbidity of 2.29% (123/5,382) (95% CI, 1.89%–2.68%) in the prepandemic period and 1.46% (66/4,521) (95% CI, 1.11%–1.81%) in the pandemic period. NEC morbidity showed resurgent characteristics in 2021. When prepandemic coinfections were excluded, most cases of NEC with bloodstream infections in the prepandemic period were attributable to Gram-negative bacteria (27/32, 84.38%), mainly Klebsiella pneumoniae, while in the pandemic period they were attributable to Gram-positive bacteria (10/18, 55.56%), mainly Staphylococcus aureus. Antimicrobial susceptibility testing revealed that Klebsiella pneumoniae was 100% sensitive to meropenem, imipenem, ciprofloxacin and levofloxacin and 100% resistant to ampicillin. Staphylococcus capitis was 100% sensitive to vancomycin, linezolid, tetracycline, cotrimoxazole and cefoxitin and 100% resistant to penicillin and benzathine.ConclusionsCOVID-19 pandemic-related interventions can reduce the morbidity of NEC and change the pathogen spectrum in patients with bloodstream infections. We need to understand the exact factors leading to these changes.
Effect of sacubitril–valsartan on left ventricular remodeling in patients with acute myocardial infarction after primary percutaneous coronary intervention: a systematic review and meta-analysis
Authors: Liu Yiheng , Sun Yue , Dai Weiran 
Published: May 2024

BackgroundSacubitril–valsartan has been widely reported for reducing the risk of cardiovascular death and improving left ventricular remodeling in patients with heart failure (HF). However, the effect of sacubitril–valsartan in patients with acute myocardial infarction (AMI) remains controversial. Therefore, we conducted this meta-analysis to investigate whether sacubitril–valsartan could reverse left ventricular remodeling and reduce cardiovascular adverse events in AMI patients after primary percutaneous coronary intervention (PPCI).Materials and methodsTwo researchers independently retrieved the relevant literature from PubMed, Embase, The Cochrane Library, China National Knowledge Infrastructure (CNKI), and the Wanfang database. The retrieval time was limited from inception to 1 June 2023. Randomized controlled trials (RCTs) meeting the inclusion criteria were included and analyzed.ResultsIn total, 21 RCTs involving 2442 AMI patients who underwent PPCI for revascularization were included in this meta-analysis. The meta-analysis showed that compared with the angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB), sacubitril–valsartan treatment in AMI patients after PPCI significantly reduced left ventricular end-diastolic dimension (LVEDD) (weighted mean difference (WMD) −3.11, 95%CI: −4.05∼−2.16, p &lt; 0.001), left ventricular end-diastolic volume (LVEDV) (WMD −7.76, 95%CI: −12.24∼−3.27, p = 0.001), left ventricular end-systolic volume (LVESV) (WMD −6.80, 95%CI: −9.45∼−4.15, p &lt; 0.001) and left ventricular end-systolic dimension (LVESD) (WMD −2.53, 95%CI: −5.30–0.24, p &lt; 0.001). Subgroup analysis according to the dose of sacubitril–valsartan yielded a similar result. Meanwhile, PPCI patients using sacubitril–valsartan therapy showed lower risk of major adverse cardiac events (MACE) (OR = 0.36, 95%CI: 0.28–0.46, p &lt; 0.001), myocardial reinfarction (OR = 0.54, 95%CI: 0.30–0.98, p = 0.041) and HF (OR = 0.35, 95%CI: 0.26–0.47, p &lt; 0.001) without increasing the risk of renal insufficiency, hyperkalemia, or symptomatic hypotension. At the same time, the change of LV ejection fraction (LVEF) (WMD 3.91, 95%CI: 3.41–4.41, p &lt; 0.001), 6 min walk test (6MWT) (WMD 43.56, 95%CI: 29.37–57.76, p &lt; 0.001) and NT-proBNP level (WMD −130.27, 95%CI: −159.14∼−101.40, p &lt; 0.001) were statistically significant.ConclusionIn conclusion, our meta-analysis indicates that compared with ACEI/ARB, sacubitril–valsartan may be superior to reverse left ventricular remodeling, improve cardiac function, and effectively reduce the risk of MACE, myocardial reinfarction, and HF in AMI patients after PPCI during follow-up without increasing the risk of adverse reactions including renal insufficiency, hyperkalemia, and symptomatic hypotension.
Indirect search of heavy neutral leptons using the DUNE near detector
Authors: Carbajal S. , Gago A. M. 
Published: May 2024

We evaluate the potential of the DUNE near detector (DUNEND) for establishing bounds for heavy neutral leptons (HNLs). This is achieved by studying how the presence of HNLs affects the production rates of active neutrinos, therefore creating a deficit in the neutrino charged current (CC) events at the LArTPC of the DUNEND. The estimated bounds on HNLs are calculated for masses between 1 eV and 500 MeV. We consider 10 years of operation (five in neutrino and antineutrino modes) and obtain limits of |Uμ4|2 &lt; 9 × 10−3 (4 × 10−2) and |Ue4|2 &lt; 7 × 10−3 (3 × 10−2) for masses below 10 MeV and a 5% (20%) overall normalization uncertainty in the neutrino charged current event rate prediction. These limits, within the region of masses below 2 (10) MeV, are better than those that can be achieved by DUNE direct searches for the case of a 5% (20%) uncertainty. When a conservative 20% uncertainty is present, our limits can only improve current constraints on |Ue4|2 by up to a factor of 3 in a small region of approximately 5 eV and set limits on |Uμ4|2 in a mass region free of constraints (40 eV–1 MeV).
Insights into the role of PGF2α in canine periparturient myometrium
Authors: Jungmann Carolin , Dyhrberg Haubuff Signe , Packeiser Eva-Maria , Körber Hanna , Reichler Iris Margaret , Balogh Orsolya , Mazzuoli-Weber Gemma , Goericke-Pesch Sandra 
Published: May 2024

Parturition in dogs is subjected to complex hormonal regulation, with the involvement of prostaglandin F2α (PGF2α) still not fully understood. To investigate uterine inertia (UI), the most prevalent maternal reason for dystocia in the bitch, a better understanding of undisturbed uterine, especially myometrial function, is crucial. Our aim was to gain deeper insights into the role of PGF2α in the canine parturient myometrium. Uterine biopsies were obtained during medically indicated cesarean sections. To test for stimulatory effects of PGF2α in vitro, circular and longitudinal myometrial layer tissue strips were challenged with 50 pM, 0.5 µM, and 50 µM PGF2α. Prostaglandin-endoperoxide synthase 2 (PTGS2) and PGF2α-receptor (PTGFR) mRNA expressions were compared between primary UI (PUI) and obstructive dystocia (OD) samples in isolated parturient myometrium. PTGFR protein expression was assessed in full thickness uterine samples. PGF2α concentrations were analyzed in canine interplacental tissue around term. In the organ bath, the contractile response to PGF2α was limited to the circular layer at the highest dosage. Correspondingly, PTGFR immunohistochemical staining was significantly stronger in the circular layer (p ≤ 0.01). PTGS2 gene expression did not differ between PUI and OD, whereas PTGFR gene expression could not be quantified. Local uterine PGF2α concentrations correlated negatively with serum P4 levels and were the highest during prepartum luteolysis while being significantly lower in PUI. Conclusively, despite the significant increase in local PGF2α concentrations at birth, confirming the interplacental tissue as a production site, our results suggest that PGF2α might affect uterine contractility during labor, mainly indirectly.
Transcriptomics reveal useful resources for examining fruit development and variation in fruit size in Coccinia grandis
Authors: Panda Mitrabinda , Pradhan Seema , Mukherjee Pulok K. 
Published: May 2024

IntroductionThe Cucurbitaceae family comprises many agronomically important members, that bear nutritious fruits and vegetables of great economic importance. Coccinia grandis, commonly known as Ivy gourd, belongs to this family and is widely consumed as a vegetable. Members of this family are known to display an impressive range of variation in fruit morphology. Although there have been studies on flower development in Ivy gourd, fruit development remains unexplored in this crop.MethodsIn this study, comparative transcriptomics of two Ivy gourd cultivars namely “Arka Neelachal Kunkhi” (larger fruit size) and “Arka Neelachal Sabuja” (smaller fruit size) differing in their average fruit size was performed. A de novo transcriptome assembly for Ivy gourd was developed by collecting fruits at different stages of development (5, 10, 15, and 20 days after anthesis i.e. DAA) from these two varieties. The transcriptome was analyzed to identify differentially expressed genes, transcription factors, and molecular markers.ResultsThe transcriptome of Ivy gourd consisted of 155205 unigenes having an average contig size of 1472bp. Unigenes were annotated on publicly available databases to categorize them into different biological functions. Out of these, 7635 unigenes were classified into 38 transcription factor (TF) families, of which Trihelix TFs were most abundant. A total of 11,165 unigenes were found to be differentially expressed in both the varieties and the in silico expression results were validated through real-time PCR. Also, 98768 simple sequence repeats (SSRs) were identified in the transcriptome of Ivy gourd.DiscussionThis study has identified a number of genes, including transcription factors, that could play a crucial role in the determination of fruit shape and size in Ivy gourd. The presence of polymorphic SSRs indicated a possibility for marker-assisted selection for crop breeding in Ivy gourd. The information obtained can help select candidate genes that may be implicated in regulating fruit development and size in other fruit crops.
Coming back together: a qualitative survey study of coping and support strategies used by people to cope with extended difficulties after the use of psychedelic drugs
Authors: Robinson Oliver C. , Evans Jules , Luke David , McAlpine Rosalind , Sahely Aneta , Fisher Amy , Sundeman Stian , Ketzitzidou Argyri Eirini , Murphy-Beiner Ashleigh , Michelle Katrina , Prideaux Ed 
Published: May 2024

IntroductionA growing body of literature is investigating the difficulties that some individuals encounter after psychedelic experiences. Existing research has explored the nature and predictors of these difficulties; however, a research gap exists in understanding how individuals endeavour to cope with such difficulties.MethodsThe current study collected data from an international cohort of 608 participants who reported experiencing difficulties that persisted for at least one day after a psychedelic experience. They provided written data on how they used coping strategies to alleviate these difficulties. The qualitative analysis of the written data on coping was conducted using Structured Tabular Thematic Analysis.ResultsA wide range of individual and social coping strategies were employed that were found helpful. The most common individual strategies were meditation and prayer, followed by self-educational activities such as reading and journaling. The most prevalent forms of social coping involved seeking support from friends or family members, followed by obtaining assistance from a therapist or coach. Features of social coping that were reported to be helpful included feeling heard/accepted, a non-judgemental attitude and sharing similar experiences.DiscussionOur findings hold potential for informing the design of therapeutic interventions and educational resources aimed at enhancing positive outcomes for those experiencing extended difficulties after psychedelic use.
Associations between repetitive head impact exposure and midlife mental health wellbeing in former amateur athletes
Authors: Buddenbaum Claire V. , Recht Grace O. , Rodriguez Adriana K. , Newman Sharlene D. , Kawata Keisuke 
Published: May 2024

IntroductionRepetitive head impacts (RHI) have been suggested to increase the risk of developing a neurodegenerative disease, and many of these individuals develop a preceding mental health diagnosis. Given the lack of studies among amateur athletes, this study aimed to examine mental health outcomes in middle-aged amateur athletes who have been exposed to RHI through contact sport participation.MethodsThis is a single site, cohort study involving former amateur athletes aged between 30 and 60 with at least 10 years of organized contact or non-contact sport participation. All participants completed demographic and mental health questionnaires. Mental health outcomes included symptoms related to depression, anxiety, post-traumatic stress disorder (PTSD), attention deficit hyperactive disorder (ADHD), and aggression. Self-reported data on mental health diagnoses and associated prescription were elicited and used to estimate odds ratios (OR).ResultsData from 41 contact athletes and 22 age/sex-matched non-contact athletes were available for analysis. The contact group exhibited a 2.25-fold higher likelihood of being diagnosed with mental health disorders and 1.29-fold higher likelihood of using associated medications compared to the non-contact group. The contact group reported significantly higher PTSD-related symptoms [4.61 (0.03,9.2), p=0.05] compared to the non-contact control group. While not statistically significant, the contact group showed increased depressive [2.37 (0.05, 4.79), p=0.07] and ADHD symptoms [4.53 (0.51, 9.57), p=0.08] compared to controls. In a secondary analysis, a distinct trend emerged within the contact group, revealing pronounced elevations in mental health symptoms among individuals with lower socioeconomic status (&lt;$50,000/year) compared to higher income subgroups, and these symptoms decreased as income levels rose [depression: -3.08 (-4.47, -1.7), p&lt;0.001; anxiety: -1.95 (-3.15, -0.76), p=0.002; ADHD: -4.99 (-8.28, -1.69), p=0.004; PTSD: -4.42 (-7.28, -1.57), p=0.003; aggression: -6.19 (-11.02, -1.36), p=0.01]. This trend was absent in the non-contact control group.DiscussionOur data suggest that even individuals at the amateur level of contact sports have an increased likelihood of being diagnosed with mental health disorders or experiencing mental health symptoms compared to non-contact athletes. Our findings indicate that socioeconomic status may have an interactive effect on individuals’ mental health, particularly among those with a long history of RHI exposure.
The impact of internet use on adolescents’ health: empirical evidence from China
Authors: Du Nianyu , Liu Lele , Zhang Lianpan , Yin Shijiu 
Published: May 2024

BackgroundWith the continuous improvement in economic levels in various countries and the rapid development of the Internet, adolescents’ Internet use has become increasingly frequent. Many studies have explored the relationship between Internet use and adolescent health, but the possible mechanisms involved are unclear, and few have focused on Chinese adolescents.MethodsBased on the data from the China Family Panel Studies 2010, 2014, 2016, 2018, and 2020, this study used the ordered probit model and OLS model to explore the impact of Internet use on self-rated health and mental health of Chinese adolescents and analyzed the possible mechanisms and heterogeneity involved.ResultsThe results revealed that adolescents’ Internet use negatively affected their physical and mental health. Parent-child conflict, academic performance, and self-efficacy were the important mechanisms of internet use affecting adolescents’ health. Moreover, the negative effects of Internet use on adolescents’ physical and mental health were heterogeneous in boarding, mother’s education level, and family per capita income.ConclusionAdolescents exhibit a pattern of using the internet that influences their health status. Our finding that internet use may decrease adolescents’ health provides important insights into understanding the relationship between internet use behavior and adolescents’ health and suggests that intervention should be taken on adolescents’ internet use.