bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of a novel prognostic signature based on m6A/m5C/m1A-related genes in hepatocellular carcinoma
Authors: Xiao Yu , Li Jinluan , Wu Junxin 
Published: July 2023

Abstract
Background
RNA methylation modification plays an important role in cancers. This study sought to examine the association between m6A/m5C/m1A-related genes and hepatocellular carcinoma (HCC).

Methods
Gene expression and clinical data of HCC patients were obtained from the TCGA database. Unsupervised consensus clustering was performed according to the expression of m6A/m5C/m1A-related genes in HCC. The relationships among prognosis, clinicopathological features and molecular subtypes were analyzed. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to establish the m6A/m5C/m1A-related gene prognostic signature. Furthermore, the prognostic signature was validated based on the ICGC dataset. RT‒qPCR was used to detect the expression of the model genes in HCC. Clinicopathological features, functional enrichment, gene mutations, immune cell infiltration, and immunotherapy response in different risk groups were analyzed. A nomogram based on risk score and stage was constructed to predict HCC patient prognosis.

Results
Two m6A/m5C/m1A-related molecular subtypes were identified in HCC, and the prognosis of cluster C1 was worse than that of cluster C2 (p < 0.001). Highly expressed genes in cluster C1 are significantly correlated with G3-4, T3-4, stage III-IV (p < 0.05). An m6A/m5C/m1A-related prognostic signature was established and validated. The RT‒qPCR results showed that the risk signature genes were significantly upregulated in liver cancer tissue (p < 0.05). The prognosis of HCC patients in the high-risk group was worse than that of those in the low-risk group (p < 0.05). Multivariate Cox analysis indicated that the risk score was an independent factor predicting prognosis in HCC patients. ssGSEA revealed that the risk score correlated with the tumor immune microenvironment in HCC. Gene mutation analysis showed that the tumor mutation burden of patients in the high-risk group was much higher (p < 0.05), and the prognosis of HCC patients with high risk scores and high mutation burden was the worst (p = 0.007). A nomogram combining risk scores with clinicopathological features showed performed well in predicting HCC prognosis.

Conclusions
The m6A/m5C/m1A-related genes could predict the prognosis and tumor microenvironment features of HCC and can be important biomarkers relevant to the immunotherapy response.
Broadly neutralizing human antibodies against Omicron subvariants of SARS-CoV-2
Authors: Chiang Hsiao-Ling , Liang Kang-Hao , Lu Ruei-Min , Kuo Ting-Wen , Lin Yi‑Ling , Wu Han-Chung 
Published: July 2023

Abstract
Background
The COVID-19 pandemic continues to pose a significant worldwide threat to human health, as emerging SARS-CoV-2 Omicron variants exhibit resistance to therapeutic antibodies and the ability to evade vaccination-induced antibodies. Here, we aimed to identify human antibodies (hAbs) from convalescent patients that are potent and broadly neutralizing toward Omicron sublineages.

Methods
Using a single B-cell cloning approach, we isolated BA.5 specific human antibodies. We further examined the neutralizing activities of the most promising neutralizing hAbs toward different variants of concern (VOCs) with pseudotyped virus.

Results
Sixteen hAbs showed strong neutralizing activities against Omicron BA.5 with low IC50 values (IC50 < 20 ng/mL). Among four of the most promising neutralizing hAbs (RBD-hAb-B22, -B23, -B25 and -B34), RBD-hAb-B22 exhibited the most potent and broad neutralization profiles across Omicron subvariant pseudoviruses, with low IC50 values (7.7–41.6 ng/mL) and a low PRNT50 value (3.8 ng/mL) in plaque assays with authentic BA.5. It also showed potent therapeutic effects in BA.5-infected K18-hACE2 mice.

Conclusions
Thus, our efficient screening of BA.5-specific neutralizing hAbs from breakthrough infectious convalescent donors successfully yielded hAbs with potent therapeutic potential against multiple SARS-CoV-2 variants.
Role of mitochondrial alterations in human cancer progression and cancer immunity
Authors: Wang Sheng-Fan , Tseng Ling-Ming , Lee Hsin-Chen 
Published: July 2023

AbstractDysregulating cellular metabolism is one of the emerging cancer hallmarks. Mitochondria are essential organelles responsible for numerous physiologic processes, such as energy production, cellular metabolism, apoptosis, and calcium and redox homeostasis. Although the “Warburg effect,” in which cancer cells prefer aerobic glycolysis even under normal oxygen circumstances, was proposed a century ago, how mitochondrial dysfunction contributes to cancer progression is still unclear. This review discusses recent progress in the alterations of mitochondrial DNA (mtDNA) and mitochondrial dynamics in cancer malignant progression. Moreover, we integrate the possible regulatory mechanism of mitochondrial dysfunction–mediated mitochondrial retrograde signaling pathways, including mitochondrion-derived molecules (reactive oxygen species, calcium, oncometabolites, and mtDNA) and mitochondrial stress response pathways (mitochondrial unfolded protein response and integrated stress response) in cancer progression and provide the possible therapeutic targets. Furthermore, we discuss recent findings on the role of mitochondria in the immune regulatory function of immune cells and reveal the impact of the tumor microenvironment and metabolism remodeling on cancer immunity. Targeting the mitochondria and metabolism might improve cancer immunotherapy. These findings suggest that targeting mitochondrial retrograde signaling in cancer malignancy and modulating metabolism and mitochondria in cancer immunity might be promising treatment strategies for cancer patients and provide precise and personalized medicine against cancer.
Macrophage’s role in solid tumors: two edges of a sword
Authors: Jahandideh Arian , Yarizadeh Mahsa , Noei-Khesht Masjedi Maryam , Fatehnejad Mina , Jahandideh Romina , Soheili Roben , Eslami Yeganeh , Zokaei Maryam , Ahmadvand Ardavan , Ghalamkarpour Nogol , Kumar Pandey Rajan , Nabi Afjadi Mohsen , payandeh Zahra 
Published: July 2023

AbstractThe tumor microenvironment is overwhelmingly dictated by macrophages, intimately affiliated with tumors, exercising pivotal roles in multiple processes, including angiogenesis, extracellular matrix reconfiguration, cellular proliferation, metastasis, and immunosuppression. They further exhibit resilience to chemotherapy and immunotherapy via meticulous checkpoint blockades. When appropriately stimulated, macrophages can morph into a potent bidirectional component of the immune system, engulfing malignant cells and annihilating them with cytotoxic substances, thus rendering them intriguing candidates for therapeutic targets. As myelomonocytic cells relentlessly amass within tumor tissues, macrophages rise as prime contenders for cell therapy upon the development of chimeric antigen receptor effector cells. Given the significant incidence of macrophage infiltration correlated with an unfavorable prognosis and heightened resistance to chemotherapy in solid tumors, we delve into the intricate role of macrophages in cancer propagation and their promising potential in confronting four formidable cancer variants—namely, melanoma, colon, glioma, and breast cancers.
Virtual and augmented reality in biomedical engineering
Authors: Taghian Aya , Abo-Zahhad Mohammed , Sayed Mohammed S. , Abd El-Malek Ahmed H. 
Published: July 2023

Abstract
Background
In the future, extended reality technology will be widely used. People will be led to utilize virtual reality (VR) and augmented reality (AR) technologies in their daily lives, hobbies, numerous types of entertainment, and employment. Medical augmented reality has evolved with applications ranging from medical education to picture-guided surgery. Moreover, a bulk of research is focused on clinical applications, with the majority of research devoted to surgery or intervention, followed by rehabilitation and treatment applications. Numerous studies have also looked into the use of augmented reality in medical education and training.

Methods
Using the databases Semantic Scholar, Web of Science, Scopus, IEEE Xplore, and ScienceDirect, a scoping review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. To find other articles, a manual search was also carried out in Google Scholar. This study presents studies carried out over the previous 14 years (from 2009 to 2023) in detail. We classify this area of study into the following categories: (1) AR and VR in surgery, which is presented in the following subsections: subsection A: MR in neurosurgery; subsection B: spine surgery; subsection C: oral and maxillofacial surgery; and subsection D: AR-enhanced human-robot interaction; (2) AR and VR in medical education presented in the following subsections; subsection A: medical training; subsection B: schools and curriculum; subsection C: XR in Biomedicine; (3) AR and VR for rehabilitation presented in the following subsections; subsection A: stroke rehabilitation during COVID-19; subsection B: cancer and VR, and (4) Millimeter-wave and MIMO systems for AR and VR.

Results
In total, 77 publications were selected based on the inclusion criteria. Four distinct AR and/or VR applications groups could be differentiated: AR and VR in surgery (N = 21), VR and AR in Medical Education (N = 30), AR and VR for Rehabilitation (N = 15), and Millimeter-Wave and MIMO Systems for AR and VR (N = 7), where N is number of cited studies. We found that the majority of research is devoted to medical training and education, with surgical or interventional applications coming in second. The research is mostly focused on rehabilitation, therapy, and clinical applications. Moreover, the application of XR in MIMO has been the subject of numerous research.

Conclusion
Examples of these diverse fields of applications are displayed in this review as follows: (1) augmented reality and virtual reality in surgery; (2) augmented reality and virtual reality in medical education; (3) augmented reality and virtual reality for rehabilitation; and (4) millimeter-wave and MIMO systems for augmented reality and virtual reality.
Surgery for primary malignant tumors of the abdominal wall: experiences of three African surgical oncology units and review of the literature
Authors: Zongo Nayi , Djiguemde Adeline R. , Yameogo Paratyandé Bonaventure , Ka Sidy , Traoré Bangaly , Dem Ahmadou 
Published: July 2023

Abstract
Background and objectives
Tumors of the abdominal wall are uncommon but diverse. The surgical challenge is double. The tumor must be completely removed and the abdominal wall repaired. Our aim was to describe the indications, techniques, and results of surgery on these tumors in an African context.

Methods
Retrospective, multicentric and descriptive study conducted in three West African surgical oncology units. We included all abdominal wall tumors followed up between January 2010 and October 2022. Histological type, size, surgical procedure, and method of abdominal wall repair were considered. Survival was calculated using the Kaplan–Meier method and comparisons of proportions were made using the Student t test.

Results
We registered 62 tumors of the abdominal wall and we operated on 41 (66.1%). The mean size of the tumors was 14.3 ± 26 cm. Dermatofibrosarcoma and desmoid tumor were present in 33 and 3 cases respectively. In 31.7% of cases in addition to the tumour, the resections carried away the muscular aponeurotic plane. Parietal resections required the use of a two-sided prosthesis in 6 cases. In 13 cases, we used skin flaps. The resections margins were invaded in 5 cases and revision surgery was performed in all of them. Incisional hernia was noticed in 2 cases. The tumor recurrence rate was 12.2% with an average time of 13 months until occurrence. Overall survival at 3 years was 80%.

Conclusions
Surgery is the mainstay of treatment for abdominal wall tumors. It must combine tumor resections and parietal repair. Cancer surgeons need to be trained in abdominal wall repair.
Origin, impacts, and potential solutions to the fragmentation of the Mexican health system: a consultation with key actors
Authors: Gómez-Dantés Octavio , Flamand Laura , Cerecero-García Diego , Morales-Vazquez Mariana , Serván-Mori Edson 
Published: July 2023

Abstract
Background
One of the central debates in health policy is related to the fragmentation of health systems. Fragmentation is perceived as a major obstacle to UHC. This article presents the results of a consultation with a group of actors of the Mexican policy arena on the origins and impacts of the fragmentation of the Mexican health system.

Methods
We used a consultation to nine key actors to collect thoughts on the fragmentation of the Mexican health system. The group included national and local decision makers with experience in health care issues and researchers with background in health systems and/or public policies. The sessions were recorded, transcribed verbatim and analyzed thematically.

Results
Participants defined the term ‘fragmentation’ as the separation of the various groups of the population based on characteristics which define their access to health care services. This is a core characteristic of health systems in Latin America (LA). In general, those affiliated to social security institutions have a higher per capita expenditure than those without social security, which translates into differential health benefits. According to the actors in this consultation, fragmentation is the main structural problem of the Mexican health system. Actors agreed that the best way to end fragmentation is through the creation of a universal health system. Defragmentation plans should include a research component to document the impacts of fragmentation, and design and test the instruments needed for the integration process.

Conclusions
First, health system fragmentation in Mexico has created problems of equity since different population groups have unequal access to public resources and different health benefits. Second, Mexico needs to move beyond the fragmentation of its health system and guarantee, through its financial integration, access to the same package of health services to all its citizens. Third, defragmentation plans should include a research component to document the impacts of fragmentation, and design and test the instruments needed for the integration process. Fourth, defragmentation of health systems is not an easy task because there are vested interests that oppose its implementation. Political strategies to meet the resistance of these groups are an essential component of any defragmentation plan.
From trials to communities: implementation and scale-up of health behaviour interventions
Authors: McCrabb Sam , Hall Alix , McKay Heather , Gonzalez Sharleen , Milat Andrew , Bauman Adrian , Sutherland Rachel , Wolfenden Luke 
Published: July 2023

Abstract
Background
To maximise their potential benefits to communities, effective health behaviour interventions need to be implemented, ideally ‘at scale’, and are often adapted as part of this. To inform future implementation and scale-up efforts, this study broadly sought to understand (i) how often health behaviour interventions are implemented in communities, (ii) the adaptations that occur; (iii) how frequency it occurred ‘at scale’; and (iv) factors associated with ‘scale-up’.

Methods
A cross-sectional survey was conducted of corresponding authors of trials (randomised or non-randomised) assessing the effects of preventive health behaviour interventions. Included studies of relevant Cochrane reviews served as a sampling frame. Participants were asked to report on the implementation and scale-up (defined as investment in large scale delivery by a (non)government organisation) of their intervention in the community following trial completion, adaptations made, and any research dissemination strategies employed. Information was extracted from published reports of the trial including assessments of effectiveness and risk of bias.

Results
Authors of 104 trials completed the survey. Almost half of the interventions were implemented following trial completion (taking on average 19 months), and 54% of those were adapted prior to doing so. The most common adaptations were adding intervention components, and adapting the intervention to fit within the local service setting. Scale-up occurred in 33% of all interventions. There were no significant associations between research trial characteristics such as intervention effectiveness, risk of bias, setting, involvement of end-user, and incidence of scale-up. However the number of research dissemination strategies was positively associated to the odds of an intervention being scaled-up (OR = 1.50; 95% CI: 1.19, 1.88; p < 0.001).

Conclusions
Adaptation of implemented trials is often undertaken. Most health behaviour interventions are not implemented or scaled-up following trial completion. The use of a greater number of dissemination strategies may increase the likelihood of scaled up.
Interseason waning of vaccine-induced hemagglutination inhibition antibody titers and contributing factors to pre-existing humoral immunity against influenza in community-dwelling older adults 75 years and older
Authors: Wunderlich Bettina , Laskow Thomas , Li Huifen , Zhang Li , Abrams Engle , Tian Jing , Yu Jun , Chen Yiyin , Tavenier Juliette , Huang Yushu , Talaat Kawsar , Bream Jay H. , Xue Qian-Li , Pawelec Graham , Leng Sean X. 
Published: July 2023

Abstract
Background
Seasonal influenza causes significant morbidity and mortality with a disproportionately high disease burden in older adults. Strain-specific hemagglutination-inhibition (HAI) antibody titer is a well-established measure of humoral immunity against influenza and pre-vaccination HAI titer is a valuable indicator of pre-existing humoral immunity at the beginning of each influenza season in highly vaccinated older adults. While vaccine-induced HAI antibody titers are known to wane over time, accurate assessment of their interseason waning has been challenging. This is because pre-vaccination HAI titers are routinely measured using current season vaccine strain antigens instead of the prior season vaccines with which individuals were immunized; as such, they do not accurately represent residual antibody titers from prior season vaccination. This study took advantage of available pre-vaccination HAI titers measured using both current and prior season vaccine strain antigens in a longitudinal influenza immunization study with participants enrolled for multiple consecutive influenza seasons from 2014 through 2017. Influenza A virus (IAV) H3N2 and influenza B virus (IBV) strains in the vaccine formula changed in 2015 and again in 2016 season. IAV H1N1 vaccine strain remained the same from 2014 through 2016 seasons, but changed in 2017. We also investigated factors contributing to pre-existing humoral immunity.

Results
Interseason waning of HAI titers was evident, but rates of waning varied among vaccine strains and study seasons, from 18% (p = .43) to 61% (p < .01). Rates of waning were noticeably greater when pre-vaccination HAI titers were measured by the routine approach, i.e., using current season vaccine strain antigens, from 33% (p = .12) to 83% (p < .01), adjusting for age at prior study season, sex, race, and education. This was largely because the routinely measured pre-vaccination HAI titers underrepresented residual HAI titers from prior season vaccinations. Moreover, interseason antibody waning and prior season post-vaccination HAI titers had significant and independent associations with pre-vaccination HAI titers.

Conclusions
The routinely measured pre-vaccination HAI titer overestimates interseason HAI antibody waning as it underestimates residual antibody titers from prior season vaccination when virus strains in the vaccine formula change. Moreover, interseason antibody waning and prior season post-vaccination HAI titers independently contribute to pre-existing humoral immunity in this highly vaccinated, community-dwelling older adult population.
The effects of high plasma levels of Aβ1-42 on mononuclear macrophage in mouse models of Alzheimer’s disease
Authors: Li Chunrong , Liu Kangding , Zhu Jie , Zhu Feiqi 
Published: July 2023

AbstractMore and more evidences are proving that microglia play a crucial role in the pathogenesis of Alzheimer’s disease (AD) and the plasma Aβ1-42 levels significantly increased 15 years before the onset of dominantly inherited AD. However, the effects of high plasma levels of Aβ1-42 on mononuclear macrophage, the peripheral counterparts of microglia, remain unclear. In the present study, we used APP/PS1 transgenic (Tg) mice and a parabiotic model of wild type (Wt) mice and Tg mice (Parabiotic Wt-Tg, Pa (Wt-Tg)) to investigate the effects of high plasma levels of Aβ1-42 on peripheral mononuclear macrophage. Our results showed that in the early stage of Tg mice (7 months) and Pa (Wt-Tg) mice (4 months), the proportions of pro-inflammatory macrophages in peritoneal cavity, myeloid derived suppressor cells (MDSCs) in spleen, granulocyte-monocyte progenitors (GMPs) in bone marrow, and the plasma levels of interleukin-6 (IL-6) were significantly decreased. While the proportions of pro-inflammatory macrophages, MDSCs, GMPs, and the plasma levels of IL-6 and tumor necrosis factor (TNF)-α, as well as the numbers of bone marrow-derived macrophages (BMDMs) in mice brain were increased in the late stage of Tg mice (11 months) and Pa (Wt-Tg) mice (8 months). In addition, the proportions of monocytes in spleen and the proliferation of bone marrow cells (BMCs) were enhanced consistently, and the phagocytic function of macrophages kept stably after high plasma levels of Aβ1-42 sustaining stimulation. These results demonstrated that high plasma levels of Aβ1-42 play a biphasic regulating role at different stages of the disease, namely inhibiting effects on peripheral pro-inflammatory macrophages in the early stage of AD model, while promoting effects in the late stage of AD model. The mechanism behind this may be associated with their effects on MDSCs in spleen and myeloid progenitor cells in bone marrow. Therefore, intervening the effects of plasma Aβ1-42 on pro-inflammatory macrophages might offer a new therapeutic approach to AD.