bluuebunny/crossref_metadata_2025_split huggingface dataset:
ATG4B and pS383/392-ATG4B serve as potential biomarkers and therapeutic targets of colorectal cancer
Authors: Hu Wan-Hsiang , Liu Ting-Ting , Liu Pei-Feng , Morgan Paul , Lin I-Ling , Tsai Wei-Lun , Cheng Yi-Yun , Hsieh Ang-Tsen , Hu Tsung-Hui , Shu Chih-Wen 
Published: April 2023

Abstract
Background
Autophagy related protease 4B (ATG4B) is a protease required for autophagy processing, which is strongly implicated in cancer progression. Phosphorylation of ATG4B is crucial for activation of its protease activity. However, little is known about the relationship of ATG4B and its phosphorylated form at Ser 383 and 392 sites (pS383/392-ATG4B), with clinical outcomes, particularly in colorectal cancer (CRC).

Methods
The ATG4B gene expression in CRC patients was obtained from The Cancer Genome Atlas (TCGA) database to analyze its clinical relevance. Tissue microarrays composed of 118 CRC patient specimens were used to determine the associations of ATG4B and pS383/392-ATG4B protein levels with prognosis. The biological functions of ATG4B in CRC cells were inspected with cell proliferation, mobility and spheroid culture assays.

Results
ATG4B gene expression was elevated in tumor tissues of CRC patients compared to that in adjacent normal tissues and high level of ATG4B expression was associated with poor survival. Similarly, protein levels of ATG4B and pS383/392-ATG4B were highly correlated with worse overall survival and disease-free survival. Stratification analysis results showed that high level of ATG4B had significantly higher risk of mortality in males and elderly patients compared to those female patients and patients 60 years or younger. In contrast, multivariate Cox’s regression analysis indicated that high level of pS383/392-ATG4B was significantly linked to unfavorable overall survival and disease-free survival of males and elderly patients, whereas, it had no correlation with female patients and patients 60 years or younger. Moreover, high level of ATG4B was positively associated with increased mortality risk in patients with advanced AJCC stages (III and IV) and lymph node invasion (N1 and N2) for both overall survival and disease-free survival. Nevertheless, high level of pS383/392-ATG4B was positively correlated with increased mortality risk in patients with early AJCC stages (I and II) and without lymph node invasion (N0). In addition, silencing ATG4B attenuated migration, invasion, and further enhanced the cytotoxic effects of chemotherapeutic drugs in two and three-dimensional cultures of CRC cells.

Conclusions
Our results suggest that ATG4B and pS383/392-ATG4B might be suitable biomarkers and therapeutic targets for CRC.
Family and domestic violence policy discourses and narratives: implications for Emergency Departments and communities in rural Australia
Authors: Moore Sheree , Fox Rachael , Nic Giolla Easpaig Bróna , Deravin Linda 
Published: April 2023

Abstract
Background
Australian data has indicated that the frequency and severity of family and domestic violence (FDV) tends to increase with remoteness. Rural communities rely on Emergency Departments (ED) within public hospitals for general health and safety needs. Public health departments within Australia are strongly influenced by Government policies which can define ‘health problems’ and limit institutional responses to patients presenting with FDV. The current study therefore aimed to critically examine FDV Australian Government policies to explore how policy meanings could potentially impact on ED staff and individuals within rural communities.

Methods
Foucauldian Discourse Analysis and Policy Narrative Analysis were used to examine 9 policy documents which represented national, state/territory and clinical practice levels. Publication dates ranged from 2006 to 2020.

Results
A total of 8 discourses were identified, with each one providing a unique construction of the target problem and determining the potential agency of health professionals and subjects of FDV. Discourses combined to produce an overall narrative within each policy document. Narrative constructions of the target problem were compared which produced three narrative themes: 1) Deficit Subject Narratives; 2) Object Oriented Narratives; and 3) Societal Narratives.

Conclusion
The results reflected a transition in the meaning of FDV within Australian society and over the past decade, with policies trending away from Deficit Subject Narratives and towards Object Oriented or Societal Narratives. Institutional systems, sociohistorical context and broader societal movements may have shaped this transition by stagnating policy meanings or introducing new insights that expanded the possibilities of understanding and action. Narratives produced assumptions which significantly altered the relevance and agency of individuals and groups when applied to a rural ED setting. As FDV was moved out of the clinical space and into the public domain, the agency of health professionals was reduced, while the values and strengths of FDV subjects and rural communities were potentially recognised. Later policies provided contextual specificity and meaning fluidity that could benefit diverse groups within rural areas; however, the expectation for ED staff to learn from their communities and challenge institutionalised approaches to FDV requires careful consideration in relation to rural hospital systems and resources.
The buffering effect of social capital for daily mental stress in an unequal society: a lesson from Seoul
Authors: Kang Sungik , Lee Joo-Lim , Koo Ja-Hoon 
Published: April 2023

AbstractThis study attempted to illustrate whether mental health deterioration could be alleviated by high social capital in an environment with high economic inequality. Daily mental stress was employed as a mental health factor when analyzing the association with economic inequality in the Seoul Survey data. Regarding social capital, community trust and altruism were included as cognitive dimensions, and participation and cooperation were included as structural dimensions in each model. The first finding showed a significantly positive relationship between economic inequality and daily stress, meaning that, like other mental health problems, daily mental stress is also high in regions with high economic inequality. Second, the slope of the daily stress increased in respondents with high social trust and participation was alleviated in an economically unequal environment. This indicates that social trust and participation have a buffering effect by moderating the slope of daily stress in societies with high inequality. Third, the buffering effect differs depending on the social capital factor. The buffering effect of trust and participation showed in an unequal environment, while the buffering effect of cooperation showed regardless of the unequal environment. In summary, social capital factors showed the effect of relieving daily mental stress in the relationship with economic inequality. Also, the buffering effect of social capital on mental health may show different aspects for each element.
Experience-based health state valuation using the EQ VAS: a register-based study of the EQ-5D-3L among nine patient groups in Sweden
Authors: Teni Fitsum Sebsibe , Burström Kristina , Devlin Nancy , Parkin David , Rolfson Ola ,   The Swedish Quality Register (SWEQR) Study Group, Abbott Allan , Ekström Magnus , Forssblad Magnus , Fritzell Peter , Jonsson Åsa , Landén Mikael , Möller Michael , Regardt Malin , Rosengren Björn , Schmitt-Egenolf Marcus , Vinblad Johanna , W-Dahl Annette 
Published: April 2023

AbstractBackgroundThe EQ VAS component of the EQ-5D questionnaire has been used to assess patients’ valuation of their own health besides its use for self-reporting of overall health status. The objective of the present study was to identify patients’ valuation of EQ-5D-3L health states using the EQ VAS in different patient groups over time and in comparison to the general population.MethodsData were obtained from patients from nine National Quality Registers (n = 172,070 patients) at baseline and at 1-year follow-up and compared with data from the general population (n = 41,761 participants). The correlation between EQ VAS scores and EQ-5D-3L index based on the Swedish experience-based VAS value set was assessed. Ordinary least squares (OLS) regression models were used to determine the association between EQ-5D-3L dimensions and EQ VAS valuation.ResultsEQ VAS scores showed consistency with severity of health states both at baseline and at 1-year follow-up in the nine selected EQ-5D-3L health states. The regression models showed mostly consistent decrements by severity levels in each dimension at both time points and similar to the general population. The dimension mainly associated with inconsistency was the self-care severity level three. Problems in the anxiety/depression dimension had the largest impact on overall health status in most of the patient groups and the general population.ConclusionThe study has demonstrated the important role EQ VAS can play in revealing patients’ valuation of their health and showed the variation in valuation of EQ-5D-3L dimensions and levels of severity across different patient groups.
Novel V-shaped kiss flap harvest technique for the forearm free flap in soft tissue reconstruction
Authors: Zhao Wenquan , Zhu Wenyuan , Yu Dan , Zhu Huiyong , Liu Jianhua , Ni Youkang 
Published: April 2023

Abstract
Introduction
Radial forearm flap (RFF) is widely used in oral reconstruction. However, the donor-site defect remains the main limit. In this paper, V-shaped kiss RFF (VRFF) is described as a novel technique to improve aesthetics and function of it. A retrospective study was conducted to introduce VRFF and evaluate its effect and safety.

Methods
A total of 21 patients who underwent VRFF for oral reconstruction, and 23 patients who underwent conventional RFF from February 2016 to April 2018 were included in this study. Direct comparisons were made on patient’s subjective evaluation of postoperative hand function and degree of scarring and objective donor-site function assessment including range of wrist movements and grip strength before and after surgery between the two groups.

Results
No skin grafts were used in the VRFF group, and 20 of 21 patients achieved primary healing at donor site, while all patients from the RFF group had skin grafts. And 18 of 23 patients achieved primary healing. The postoperative scar score of donor site in the VRFF group was significantly higher than that in the RFF group (3.4 vs 2.8, P = 0.035). There were no significant differences in other subjective evaluation and donor-site morbidity and hand function assessment.

Conclusion
VRFF is able to provide a new and simple method to close donor-site defect and realize a better healing in donor site.
Clinicopathological characteristics, local treatment, and prognostic factors in IE/IIE primary breast lymphoma: a retrospective study of 67 patients
Authors: Feng Ruigang , Huang Wenwen , Chen Lixuan , Min Jie , Shu Wenjun , Yu Yue , Wang Xin , Cao Xuchen , Liu Bowen 
Published: April 2023

Abstract
Introduction
Primary breast lymphoma (PBL) is a rare disease, treatment of which excerpts does not reach a consensus. This retrospective study was conducted to analyze clinical features and survival outcomes of different therapeutic methods.

Materials and methods
Records of 67 patients with stage IE/IIE primary breast lymphoma were reviewed from the medical record system. Survival information was gathered by searching the outpatient system. Clinicopathological characteristics were compared by chi-squared or Fisher’s exact tests. A comparison of survival curves was performed by log-rank tests. The Cox proportional hazard model was applied for multivariate analysis.

Results
At the median follow-up time of 65.23 months (range, 9–150 months), there were 27 (40.3%) relapses, 28 (41.8%) distant metastases, and 21 (31.3%) deaths. The 5-year progression-free survival (PFS) and overall survival (OS) were 52.1% and 72.4%. Pathological types (DLBCL vs. non-DLBCL, p = 0.001) and rituximab use (p < 0.001) were statistically associated with longer PFS in patients with PBL. Nodal sites involved and radiotherapy administration were significant predictors for 5-year OS. Multivariate analysis suggested that nodal sites involved (p = 0.005) and radiotherapy administration (p < 0.003) were independent prognostic factors for OS in patients with PBL (p < 0.05). Radical surgery was not an independent factor for patients with PBL.

Conclusions
Radiotherapy improved the survival of patients with PBL. Radical mastectomy offered no additional benefit in the treatment of PBL.
SARS-CoV-2 before and after Omicron: two different viruses and two different diseases?
Authors: Gili Renata , Burioni Roberto 
Published: April 2023

AbstractFor the first time in the history of medicine, it has been possible to describe—after a spillover—the evolution of a new human virus spreading in a non-immune population. This allowed not only to observe the subsequent emersion of variants endowed with features providing the virus with an evolutionary advantage, but also the shift of the pathways of virus replication and the acquisition of immunoevasive features. These characteristics had a remarkable influence on the diffusion of the SARS-CoV-2 and on the clinical presentation and prognosis of COVID-19, aspects that are described and commented in this review.
RETRACTED ARTICLE: Palmitoyl transferases act as novel drug targets for pancreatic cancer
Authors: Lin Zhiqing , Lv Ziru , Liu Xin , Huang Keke 
Published: April 2023

Abstract
Background
Pancreatic adenocarcinoma (PAAD) is one of the most leading causes of cancer-related death across the world with the limited efficiency and response rate of immunotherapy. Protein S-palmitoylation, a powerful post-translational lipid modification, is well-known to regulate the stability and cellular distribution of cancer-related proteins, which is mediated by a family of 23 palmitoyl transferases, namely zinc finger Asp-His-His-Cys-type (ZDHHC). However, whether palmitoyl transferases can determine tumor progression and the efficacy of immunotherapy in PAAD remains unknown.

Methods
Bioinformatics methods were used to identify differential ZDHHCs expression in PAAD. A systematic pan-cancer analysis was conducted to assess the immunological role of ZDHHC3 using RNA sequencing data from The Cancer Genome Atlas database. In vivo Panc 02 subcutaneous tumor model validated the anti-tumor effect of knockdown of ZDHHC3 or intraperitoneal injection of 2-bromopalmitate (2-BP), a typical broad-spectrum palmitoyl transferases inhibitor. Furthermore, we explored therapeutic strategies with combinations of 2-BP with PD-1/PD-L1-targeted immunotherapy in C57BL/6 mice bearing syngeneic Panc 02 pancreatic tumors.

Results
ZDHHC enzymes were associated with distinct prognostic values of pancreatic cancer. We identified that ZDHHC3 expression promotes an immunosuppressive tumor microenvironment in PAAD. 2-BP suppressed pancreatic-tumor cell viability and tumor sphere-forming activities, as well as increased cell apoptosis in vitro, without affecting normal human pancreatic ductal epithelial cells. Furthermore, genetic inactivation of ZDHHC3 or intraperitoneal injection of 2-BP impeded tumor progression in Panc 02 pancreatic tumors with enhanced anti-tumor immunity. 2-BP treatment significantly enhanced the therapeutic efficacy of PD-1/PD-L1 inhibitors in Panc 02 pancreatic tumors.

Conclusion
This study revealed some ZDHHC enzyme genes for predicting the prognosis of pancreatic cancer, and demonstrated that ZDHHC3 plays a critical oncogenic role in pancreatic cancer progression, highlighting its potential as an immunotherapeutic target of pancreatic cancer. In addition, combination therapy of 2-BP and PD-1/PD-L1 achieved synergic therapy effects in a mouse model of pancreatic cancer.
Thymic function and survival at advance ages in nursing home residents from Southern Italy
Authors: Paparazzo Ersilia , Geracitano Silvana , Lagani Vincenzo , Citrigno Luigi , Bartolomeo Denise , Aceto Mirella Aurora , Bruno Francesco , Maletta Raffaele , Passarino Giuseppe , Montesanto Alberto 
Published: April 2023

Abstract
Background
Immunosenescence is a complex process characterized by an age-related remodelling of immune system. The prominent effects of the immunosenescence process is the thymic involution and, consequently, the decreased numbers and functions of T cells. Since thymic involution results in a collapse of the T-cell receptor (TCR) repertoire, a reliable biomarker of its activity is represented by the quantification of signal joint T-cell receptor rearrangement excision circles (sjTRECs) levels. Although it is reasonable to think that thymic function could play a crucial role on elderly survival, only a few studies investigated the relationship between an accurate measurement of human thymic function and survival at old ages.

Methods and findings
By quantifying the amount sjTRECs by real-time polymerase chain reaction (PCR), the decrease in thymic output in 241 nursing home residents from Calabria (Southern Italy) was evaluated to investigate the relationship between thymic function and survival at old ages. We found that low sjTREC levels were associated with a significant increased risk of mortality at older ages. Nursing home residents with lower sjTREC exhibit a near 2-fold increase in mortality risk compared to those with sjTREC levels in a normal range.

Conclusion
Thymic function failure is an independent predictor of mortality among elderly nursing home residents. sjTREC represents a biomarker of effective ageing as its blood levels could anticipate individuals at high risk of negative health outcomes. The identification of these subjects is crucial to manage older people’s immune function and resilience, such as, for instance, to plan more efficient vaccinal campaigns in older populations.
A retrospective comparison of double-hooked locking plates versus non-locking plates in minimally invasive percutaneous plate osteosynthesis for the treatment of comminuted distal fibular fractures accompanied by tibial Pilon fractures
Authors: Liu Jun-Hong , Zhang Qiang , Wei Guo-Hua , Liu Liang , Mu Xin , Li Mao-Lin , Wu Zong-De 
Published: April 2023

Abstract
Background
Surgical approach and fixation material are crucial in the treatment of comminuted distal fibular fractures accompanied by tibial Pilon fractures. This study compared the efficacy of double-hooked locking plates and anatomic plates in minimally invasive percutaneous plate osteosynthesis (MIPPO) for the treatment of comminuted distal fibular fractures accompanied by tibial Pilon fractures.

Methods
Clinical data were collected from 96 patients diagnosed with comminuted distal fibular fractures accompanied by tibial Pilon fractures who had undergone MIPPO. Patients in the study group (n = 48) received double-hooked locking plate fixations and the control group (n = 48) received anatomical plate fixations. The operating time, intraoperative bleeding, length of hospital stays, full weight-bearing time, fracture healing time and complication rates in the two groups were compared. The quality of fracture reduction was evaluated using the Burwell–Chamley imaging scoring system; the ankle function was assessed based on the American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Score.

Results
Patients in the study group had shorter operating time, less bleeding, significantly shorter hospital stays, and shorter time to full weight-bearing as well as fracture healing compared to the control group (P < 0.05). Additionally, the post-operative complication rates were significantly lower in the study group (6.16% vs. 22.92%) (P < 0.05), but there was no significant difference in the fracture reduction rate between the two groups (P > 0.05). Patients in the study group experienced better ankle recovery than those in the control group (93.75% vs. 75.00%) (P < 0.05).

Conclusion
Double-hooked locking plates have advantages in the treatment of comminuted distal fibular fractures accompanied by tibial Pilon fractures during MIPPO due to their shorter operating time and less intraoperative bleeding, as well as shorter hospital stays, full weight-bearing time and fracture healing time, fewer complications and better ankle recovery. Therefore, double-hooked locking plates are worthy of clinical application.
Temporal transcriptome highlights the involvement of cytokine/JAK/STAT3 signaling pathway in the osteoinduction of BMSCs
Authors: Ru Xiao , Cai Peian , Tan Manli , Zheng Li , Lu Zhenhui , Zhao Jinmin 
Published: April 2023

Abstract
Background
Mesenchymal stem cells (MSCs)-based therapy offers an effective strategy for bone regeneration to solve the clinical orthopedic problems. However, the transcriptional regulation of multiple transitional stages of continuous osteogenesis from MSCs has not been fully characterized.

Methods
Bone marrow mesenchymal stem cells (BMSCs) stimulated with osteogenic induction media were utilized to construct the in vitro osteogenic differentiation model. BMSCs were harvested after induction for 0, 7, 14 and 21 days, respectively, to perform the mRNA-sequencing (mRNA-Seq). The transcription factor networks and common molecules during the osteogenesis were revealed by using the temporal transcriptome. Further verification was performed by the quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence and Western blotting.

Results
It showed that BMSCs could differentiate into osteogenic, and crucial regulator in the MAPK signaling pathway, the PPAR signaling pathway, the Toll-like receptor signaling and the Cytokine/JAK/STAT signaling pathway. PPI protein interaction analysis also suggested that three cytokines are involved in osteogenic differentiation as core genes, including leukemia inhibitory factor (LIF), interleukin-6 (IL6) and colony-stimulating factor 3 (CSF3). The osteogenic process was negatively affected by the inhibition of JAK/STAT3 signaling pathway.

Conclusions
This work might provide new insights in the crucial features of the transcriptional regulation during the osteogenesis, as well as offer important clues about the activity and regulation of the relatively long-activated Cytokine/JAK/STAT3 signaling pathway in osteoinduction of BMSCs.