bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atezolizumab plus bevacizumab in patients with child–Pugh B advanced hepatocellular carcinoma
Authors: Cheon Jaekyung , Kim Hyeyeong , Kim Han Sang , Kim Chang Gon , Kim Ilhwan , Kang Beodeul , Kim Chan , Jung Sanghoon , Ha Yeonjung , Chon Hong Jae 
Published: January 2023

Background: Atezolizumab plus bevacizumab (Ate/Bev) demonstrated promising efficacy and safety in patients with advanced hepatocellular carcinoma (HCC) in the phase III IMbrave150 trial. However, patients with Child–Pugh B HCC were excluded in the abovementioned prospective trial. Therefore, we aimed to investigate the efficacy and safety of Ate/Bev in patients with Child–Pugh B HCC. Methods: This multicenter retrospective study included 36 patients with Child–Pugh B advanced HCC who received Ate/Bev at four cancer referral centers between May 2020 and August 2021. Comparative analyses were performed with an independent cohort of patients with Child–Pugh A HCC from the same registry ( n = 133). Results: All patients received Ate/Bev as first-line systemic treatment for advanced HCC. The objective response and disease control rates of patients in the Child–Pugh groups B and A were 11.1% and 58.3% and 34.6% and 76.7%, respectively. The median progression-free survival (PFS) and overall survival (OS) were 3.0 months [95% confidence interval (CI), 1.7–4.3) and 7.7 months (95% CI, 4.8–10.6) in the Child–Pugh B group, whereas the median PFS and OS were 9.6 months (95% CI, 5.1–14.2) and not reached (95% CI, not available) in the Child–Pugh A group, respectively. Compared to the Child–Pugh A group, grade 3–4 adverse events (AEs) were more common in the Child–Pugh B group (44.4% versus 15.8, p < 0.001), with the most frequent grade 3–4 AEs being gastrointestinal bleeding ( n = 6, 16.7%), neutropenia ( n = 5, 13.9%), and thrombocytopenia ( n = 4, 11.1%). Conclusions: In the Child–Pugh B subgroup of patients with advanced HCC, Ate/Bev treatment showed modest clinical activity. However, due to the increased frequency of serious AEs, careful evaluation of treatment response and AE management is required in this subgroup of patients.
Fecal microbiota transplantation from young mice rejuvenates aged hematopoietic stem cells by suppressing inflammation
Authors: Zeng Xiangjun , Li Xiaoqing , Li Xia , Wei Cong , Shi Ce , Hu Kejia , Kong Delin , Luo Qian , Xu Yulin , Shan Wei , Zhang Meng , Shi Jimin , Feng Jingjing , Han Yingli , Huang He , Qian Pengxu 
Published: January 2023

AbstractHematopoietic stem cell (HSC) aging is accompanied by hematopoietic reconstitution dysfunction, including loss of regenerative and engraftment ability, myeloid differentiation bias, and elevated risks of hematopoietic malignancies. Gut microbiota, a key regulator of host health and immunity, has recently been reported to affect hematopoiesis. However, there is currently limited empirical evidence explaining the direct impact of gut microbiome on aging hematopoiesis. In this study, we performed fecal microbiota transplantation (FMT) from young mice to aged mice and observed a significant increment in lymphoid differentiation and decrease in myeloid differentiation in aged recipient mice. Furthermore, FMT from young mice rejuvenated aged HSCs with enhanced short-term and long-term hematopoietic repopulation capacity. Mechanistically, single-cell RNA sequencing deciphered that FMT from young mice mitigated inflammatory signals, upregulated the FoxO signaling pathway, and promoted lymphoid differentiation of HSCs during aging. Finally, integrated microbiome and metabolome analyses uncovered that FMT reshaped gut microbiota composition and metabolite landscape, and Lachnospiraceae and tryptophan-associated metabolites promoted the recovery of hematopoiesis and rejuvenated aged HSCs. Together, our study highlights the paramount importance of the gut microbiota in HSC aging and provides insights into therapeutic strategies for aging-related hematologic disorders.
Identifying cancer driver genes based on multi-view heterogeneous graph convolutional network and self-attention mechanism
Authors: Peng Wei , Wu Rong , Dai Wei , Yu Ning 
Published: January 2023

AbstractBackgroundCorrectly identifying the driver genes that promote cell growth can significantly assist drug design, cancer diagnosis and treatment. The recent large-scale cancer genomics projects have revealed multi-omics data from thousands of cancer patients, which requires to design effective models to unlock the hidden knowledge within the valuable data and discover cancer drivers contributing to tumorigenesis.ResultsIn this work, we propose a graph convolution network-based method called MRNGCN that integrates multiple gene relationship networks to identify cancer driver genes. First, we constructed three gene relationship networks, including the gene–gene, gene–outlying gene and gene–miRNA networks. Then, genes learnt feature presentations from the three networks through three sharing-parameter heterogeneous graph convolution network (HGCN) models with the self-attention mechanism. After that, these gene features pass a convolution layer to generate fused features. Finally, we utilized the fused features and the original feature to optimize the model by minimizing the node and link prediction losses. Meanwhile, we combined the fused features, the original features and the three features learned from every network through a logistic regression model to predict cancer driver genes.ConclusionsWe applied the MRNGCN to predict pan-cancer and cancer type-specific driver genes. Experimental results show that our model performs well in terms of the area under the ROC curve (AUC) and the area under the precision–recall curve (AUPRC) compared to state-of-the-art methods. Ablation experimental results show that our model successfully improved the cancer driver identification by integrating multiple gene relationship networks.
Twice evasions of Omicron variants explain the temporal patterns in six Asian and Oceanic countries
Authors: Chen Boqiang , Zhao Yanji , Jin Zhen , He Daihai , Li Huaichen 
Published: January 2023

AbstractBackgroundThe ongoing coronavirus 2019 (COVID-19) pandemic has emerged and caused multiple pandemic waves in the following six countries: India, Indonesia, Nepal, Malaysia, Bangladesh and Myanmar. Some of the countries have been much less studied in this devastating pandemic. This study aims to assess the impact of the Omicron variant in these six countries and estimate the infection fatality rate (IFR) and the reproduction number$${R}_{0}$$R0in these six South Asia, Southeast Asia and Oceania countries.MethodsWe propose a Susceptible-Vaccinated-Exposed-Infectious-Hospitalized-Death-Recovered model with a time-varying transmission rate$$\beta (t)$$β(t)to fit the multiple waves of the COVID-19 pandemic and to estimate the IFR and$${R}_{0}(t)$$R0(t)in the aforementioned six countries. The level of immune evasion and the intrinsic transmissibility advantage of the Omicron variant are also considered in this model.ResultsWe fit our model to the reported deaths well. We estimate the IFR (in the range of 0.016 to 0.136%) and the reproduction number$${R}_{0}(t)$$R0(t)(in the range of 0 to 9) in the six countries. Multiple pandemic waves in each country were observed in our simulation results.ConclusionsThe invasion of the Omicron variant caused the new pandemic waves in the six countries. The higher$${R}_{0}(t)$$R0(t)suggests the intrinsic transmissibility advantage of the Omicron variant. Our model simulation forecast implies that the Omicron pandemic wave may be mitigated due to the increasing immunized population and vaccine coverage.
Vitamin d deficiency with high parathyroid hormone levels is related to late onset SEPSIS among preterm infants
Authors: Tofe-Valera I. , Pérez-Navero J. L. , Caballero-Villarraso J. , Cañete M. D. , Villa-Jiménez R. , De la Torre-Aguilar M. J. 
Published: January 2023

Abstract
Summary
Preterm infants (PTs) are at greater risk for vitamin D deficiency, which relates to the possibility of a higher incidence of comorbidities. Our goal was twofold, 1) to monitor vitamin D, calcium, phosphorus, parathyroid hormone (PTH), matrix metalloproteinase-8 (MMP-8) serum levels at three-time points during hospitalization, and 2) to assess the association between 25-hydroxyvitamin D (25OHD) levels and outcomes in PTs.

Methods
We carried out a follow-up on 50 Caucasian PTs ≤ 32 weeks of gestational age (GA) and/or ≤ 1500 g birth weight at 28 days and at 4 months. PTs were divided into two subgroups for tests of association with clinical outcomes based on vitamin D deficient infants 25(OH) D cord blood levels: ≤ 20 ng/ml). At an initial stage, 25(OH) D levels were determined in maternal/preterm blood samples and were compared to full term delivery infants.

Results
There were no differences in 25(OH) D serum levels at birth when comparing PTs to term infants, or regarding maternal levels. A strong positive correlation was detected between maternal and neonatal 25(OH) D serum levels among PTs and term infants (r: 0.466; p < 0.001). Neonates with vitamin D deficiency did not present a higher incidence of comorbidities. PTs were classified in two subgroups based on vitamin D and PTH (group 1: vitamin D < 20 ng/mL and PTH > 60 pg/mL; group 2: vitamin D > 20 and PTH < 60 pg/mL). The PTs in group 1 showed a higher incidence of LOS (RR: 2; 95% CI: 1.31–3.55). No relationship was observed between MMP-8 serum levels and the incidence of sepsis.

Conclusions
This study did not find any evidence of an increase in preterm birth risk related to vitamin D level at birth. Vitamin D deficiency by itself is not associated with a higher incidence of comorbidities. However, the binomial vitamin D-PTH must be taken into consideration.
Claudin18.2 as a potential therapeutic target for primary ovarian mucinous carcinomas and metastatic ovarian mucinous carcinomas from upper gastrointestinal primary tumours
Authors: Wang Fujun , Yang Yao , Du Xiuzhen , Zhu Xiaoying , Hu Yanjiao , Lu Changyu , Sui Lei , Zhao Han , Song Kejuan , Yao Qin 
Published: January 2023

AbstractBackgroundThe vast majority of ovarian mucinous carcinomas are metastatic tumours derived from nonovarian primary cancers, typically gastrointestinal neoplasms. Therapy targeting claudin18.2 might be used in gastric, gastroesophageal junction and pancreatic cancers with high expression of claudin18.2. In this study, we aimed to profile the expression of claudin18.2 in primary ovarian mucinous carcinoma (POMC) and metastatic gastrointestinal mucinous carcinoma (MGMC).MethodsImmunohistochemistry was used to detect claudin 18.2 expression in whole tissue sections of ovarian mucinous carcinomas, including 32 POMCs and 44 MGMCs, 23 of which were derived from upper gastrointestinal primary tumours and 21 of which were derived from lower gastrointestinal primary tumours. Immunohistochemical studies for claudin18.2, SATB2, PAX8, CK7 and CK20 were performed in all 76 cases.ResultsAmong 76 primary and metastatic mucinous carcinomas, claudin18.2 was expressed in 56.6% (43/76) of cases. MGMCs from the upper gastrointestinal tract, including 22 derived from primary stomach tumours and one derived from a pancreas tumour, were positive for claudin 18.2 in 69.5% (16/23) of cases. MGMCs from the lower gastrointestinal tract, including 10 derived from primary appendiceal cancer and 11 derived from colorectal cancers, showed no claudin18.2 expression (0/21). The expression rate of claudin18.2 in primary ovarian mucinous neoplasms, including 22 primary ovarian mucinous carcinomas and 10 primary ovarian borderline mucinous tumours, was 84.4% (27/32). The common immunophenotypic characteristics of POMCs, upper gastrointestinal tract-derived MGMCs, and lower gastrointestinal tract-derived MGMCs were claudin18.2 + /PAX8 + /SATB2- (17/32), claudin18.2 + /PAX8-/SATB2- (16/23) and claudin18.2-/PAX8-/SATB2 + (19/21), respectively.ConclusionClaudin18.2 is highly expressed in POMCs and MGMCs derived from upper gastrointestinal tract primary tumours; therefore, claudin18.2-targeted therapy might serve as a potential therapeutic strategy for POMCs and MGMCs from the upper gastrointestinal tract.
The prevalence of violence and its association with mental health among the Iranian population in one year after the outbreak of COVID-19 disease
Authors: Kamali Koorosh , Maleki Azam , Yazdi Seyed Abbas Bagheri , Faghihzadeh Elham , Hoseinzade Zarrintaj , Hajibabaei Marzieh , Sharafi Seyedeh Elham , Noorbala Ahmad Ali 
Published: January 2023

Abstract
Background
COVID-19 spread between and across nearly every country, with considerable negative health consequences. The current study aimed to determine the prevalence of violence and its association with mental health among Iranians older than 15 years in 2020.

Methods
Data was collected through National Mental Health Survey on 24,584 Iranians older than 15 years in 2020. were analyzed to determine the prevalence of violence and its association with mental health. Multi-stage sampling method was used, and data on demographic characteristics and domestic-social violence and mental health (GHQ-28) were collected. Data analysis was administered using descriptive statistics and a chi-square test at a 95% level.

Results
The mean age of participants was 44.18 ± 16.4 years. The overall prevalence of domestic and social violence was 11.4% and 5.5%, respectively. Verbal violence was the most common type; with 61.8% and 66.8% for domestic and social violence, respectively. A suspected case of mental disorder, female gender, being younger than 25 years, living apart together, unemployment, low education, and history of COVID-19 infection presented a significant association with domestic and social violence (p > 0.05).

Conclusion
In comparison to the previous study in 2015, the prevalence of violence has increased. Therefore, domestic and social violence are the social concerns of Iranian society, indicating the necessity of appropriate interventions, particularly for those suspected of mental disorders and young women with low education levels.
Only one cluster per condition is an invalid design for a cluster randomized trial and should be re-labeled a quasi-experimental study. Response to: “Effect of behavioral activation on time and frequency domain heart rate variability in older adults with subthreshold depression: a cluster randomized controlled trial in Thailand”
Authors: Jamshidi-Naeini Yasaman , Golzarri-Arroyo Lilian , Siddique Abu Bakkar , Vorland Colby J. , Allison David B. 
Published: January 2023

AbstractAyudhaya et al. examined the effect of Behavioral Activation on daily step count and heart rate variability among older adults with depression in a study labeled a cluster randomized controlled trial (cRCT). However, only one cluster was assigned to either of the study conditions. Such a design would have zero degrees of freedom for inferential testing, because the variation due to cluster membership cannot be estimated apart from the variation due to treatment assignment. Thus, the intervention effect is completely confounded with the cluster effect. The study should be labeled a quasi-experimental study, not a cRCT. Accordingly, the numerical results should be interpreted as associations but not evidence for causal relationships.
Impacts of the COVID-19 pandemic on life and learning experiences of indigenous and non-Indigenous university and college students in Ontario, Canada: a qualitative study
Authors: Blaskovits Farriss , Bayoumi Imaan , Davison Colleen M. , Watson Autumn , Purkey Eva 
Published: January 2023

Abstract
Background
The years people spend attending university or college are often filled with transition and life change. Younger students often move into their adult identity by working through challenges and encountering new social experiences. These transitions and stresses have been impacted significantly by the COVID-19 pandemic, which has led to dramatic change in the post-secondary experience, particularly in the pandemic’s early months when colleges and universities were closed to in person teaching. The goal of this study was to identify how COVID-19 has specifically impacted the postsecondary student population in Kingston, Ontario, Canada.

Methods
The Cost of COVID is a mixed methods study exploring the social and emotional impacts of the COVID-19 pandemic, with a focus on families, youth, and urban Indigenous People. The present analysis was completed using a subset of qualitative data including Spryng.io micronarrative stories from students in college and university, as well as in-depth interviews from service providers providing services to students. A double-coded phenomenological approach was used to collect and analyze data to explore and identify themes expressed by postsecondary students and service providers who worked with postsecondary students.

Results
Twenty-six micronarratives and seven in-depth interviews were identified that were specifically relevant to the post-secondary student experience. From this data, five prominent themes arose. Impacts of the COVID-19 pandemic on the use of technology was important to the post secondary experience. The pandemic has substantial educational impact on students, in what they chose to learn, how it was taught, and experiences to which they were exposed. Health and wellbeing, physical, psychological and emotional, were impacted. Significant impacts were felt on family, community, and connectedness aspects. Finally, the pandemic had important financial impacts on students which affected their learning and their experience of the pandemic. Impacts did differ for Indigenous students, with many of the traditional cultural supports and benefits of spaces of higher education no longer being available.

Conclusion
Our study highlights important impacts of the pandemic on students of higher education that may have significant individual and societal implications going forward. Both postsecondary institutions and society at large need to attend to these impacts, in order to preserve the wellbeing of graduates, the Canadian labor market, and to ensure that the pandemic does not further exacerbate existing inequalities in post-secondary education in Canada.
Challenges of using e-health technologies to support clinical care in rural Africa: a longitudinal mixed methods study exploring primary health care nurses’ experiences of using an electronic clinical decision support system (CDSS) in South Africa
Authors: Horwood Christiane , Luthuli Silondile , Mapumulo Sphindile , Haskins Lyn , Jensen Cecilie , Pansegrouw Deidre , McKerrow Neil 
Published: January 2023

Abstract
Background
Electronic decision-making support systems (CDSSs) can support clinicians to make evidence-based, rational clinical decisions about patient management and have been effectively implemented in high-income settings. Integrated Management of Childhood Illness (IMCI) uses clinical algorithms to provide guidelines for management of sick children in primary health care clinics and is widely implemented in low income countries. A CDSS based on IMCI (eIMCI) was developed in South Africa.

Methods
We undertook a mixed methods study to prospectively explore experiences of implementation from the perspective of newly-trained eIMCI practitioners. eIMCI uptake was monitored throughout implementation. In-depth interviews (IDIs) were conducted with selected participants before and after training, after mentoring, and after 6 months implementation. Participants were then invited to participate in focus group discussions (FGDs) to provide further insights into barriers to eIMCI implementation.

Results
We conducted 36 IDIs with 9 participants between October 2020 and May 2021, and three FGDs with 11 participants in October 2021. Most participants spoke positively about eIMCI reporting that it was well received in the clinics, was simple to use, and improved the quality of clinical assessments. However, uptake of eIMCI across participating clinics was poor. Challenges reported included lack of computer skills which made simple tasks, like logging in or entering patient details, time consuming. Technical support was provided, but was time consuming to access so that eIMCI was sometimes unavailable. Other challenges included heavy workloads, and the perception that eIMCI took longer and disrupted participant’s work. Poor alignment between recording requirements of eIMCI and other clinic programmes increased participant’s administrative workload. All these factors were a disincentive to eIMCI uptake, frequently leading participants to revert to paper IMCI which was quicker and where they felt more confident.

Conclusion
Despite the potential of CDSSs to increase adherence to guidelines and improve clinical management and prescribing practices in resource constrained settings where clinical support is scarce, they have not been widely implemented. Careful attention should be paid to the work environment, work flow and skills of health workers prior to implementation, and ongoing health system support is required if health workers are to adopt these approaches (350).
Long noncoding RNAs: glycolysis regulators in gynaecologic cancers
Authors: Lv Nengyuan , Shen Siyi , Chen Qianying , Tong Jinyi 
Published: January 2023

AbstractThe three most common gynaecologic cancers that seriously threaten female lives and health are ovarian cancer, cervical cancer, and endometrial cancer. Glycolysis plays a vital role in gynaecologic cancers. Several long noncoding RNAs (lncRNAs) are known to function as oncogenic molecules. LncRNAs impact downstream target genes by acting as ceRNAs, guides, scaffolds, decoys, or signalling molecules. However, the role of glycolysis-related lncRNAs in regulating gynaecologic cancers remains poorly understood. In this review, we emphasize the functional roles of many lncRNAs that have been found to promote glycolysis in gynaecologic cancers and discuss reasonable strategies for future research.
The roles of connexins and gap junctions in the progression of cancer
Authors: Zhou Mingming , Zheng Minying , Zhou Xinyue , Tian Shifeng , Yang Xiaohui , Ning Yidi , Li Yuwei , Zhang Shiwu 
Published: January 2023

AbstractGap junctions (GJs), which are composed of connexins (Cxs), provide channels for direct information exchange between cells. Cx expression has a strong spatial specificity; however, its influence on cell behavior and information exchange between cells cannot be ignored. A variety of factors in organisms can modulate Cxs and subsequently trigger a series of responses that have important effects on cellular behavior. The expression and function of Cxs and the number and function of GJs are in dynamic change. Cxs have been characterized as tumor suppressors in the past, but recent studies have highlighted the critical roles of Cxs and GJs in cancer pathogenesis. The complex mechanism underlying Cx and GJ involvement in cancer development is a major obstacle to the evolution of therapy targeting Cxs. In this paper, we review the post-translational modifications of Cxs, the interactions of Cxs with several chaperone proteins, and the effects of Cxs and GJs on cancer.