bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and validation of novel lung adenocarcinoma subtypes and construction of prognostic models: based on cuprotosis-related genes
Authors: Wang Guangyao , Wang Anqiao , Wang Li , Xu Guanglan , Hong Xiaohua , Fang Fang 
Published: February 2023

AbstractCuprotosis is a novel and unique form of cell death that is of great value in a variety of cancers. However, the prognostic role of cuprotosis-related genes (CRGs) in lung cancer remains undetermined. We compared the expression profile of CRGs in lung adenocarcinoma (LUAD) patients, revealing the genetic alterations and inter-gene correlations of CRGs. Based on 13 CRGs, LUAD patients could be well differentiated into two molecular subgroups, and the differentially expressed genes (DEGs) in these molecular subtypes were identified. Furthermore, 10 cuprotosis pattern-related DEGs with a significant prognostic value were obtained for constructing a prognostic model. Through validation in an external validation set, the prognostic model based on the CRGs-risk score showed the robust and effective predictive ability and served as an independent prognostic indicator for LUAD patients. Therefore, combining the CRGs-risk score with multiple factors such as clinicopathological characteristics, a quantitative nomogram was developed to predict the survival and prognosis of LUAD patients, improving the clinical application value of the CRGs-risk score. In the low CRGs-risk score group, the related immune cell infiltration was increased and the immune function was activated in LUAD patients. This study may add to the knowledge of CRGs in LUAD, partly contribute to evaluating the prognosis of LUAD patients, and provide direction for the development of targeted therapy and immunotherapy.
Impact of bone-implant gap size on the interfacial osseointegration: an in vivo study
Authors: Huang Kangkang , Wu Tingkui , Lou Jigang , Wang Beiyu , Ding Chen , Gong Quan , Rong Xin , Liu Hao 
Published: February 2023

Abstract
Background
The bone-implant gap resulted from morphological mismatch between cervical bony endplates and implant footprint may have adverse impact on bone-implant interfacial osseointegration of cervical disc arthroplasty (CDA). The purpose of the study was to evaluate the impact of bone-implant gap size on the interfacial osseointegration in a rabbit animal model.

Methods
A series of round-plate implants with different teeth depth (0.5 mm, 1.0 mm, 1.5 mm and 2.0 mm) was specifically designed. A total of 48 New Zealand white rabbits were randomly categorized into four groups by the implants they received (0.5 mm: group A, 1.0 mm: group B, 1.5 mm: group C, 2.0 mm: group D). At 4th and 12th week after surgery, animals were sacrificed. Micro-CT, acid fuchsin and methylene blue staining and hematoxylin and eosin (HE) staining were conducted.

Results
At 4th week and 12th week after surgery, both micro-CT and HE staining showed more new bone formation and larger bone coverage in group A and group B than that in group C and group D. At 12th week, the bone biometric parameters were significantly superior in group C when compared with group D (p < 0.05). At 12th week, hard tissue slicing demonstrated larger portion of direct contact of new bone to the HA coating in group A and group B.

Conclusions
Bone-implant gap size larger than 1.0 mm negatively affected bone-implant osseointegration between compact bone and HA coated implant surface.
The association of dietary approaches to stop hypertension (DASH) with the odds of diabetic nephropathy and metabolic markers in women: a case–control study
Authors: Mirzababaei Atieh , Abaj Faezeh , Hajishizari Sara , Bahrampour Niki , Noori Sahar , Barekzai Ahmad Mujtaba , Hosseininasab Dorsa , Clark Cain C. T. , Mirzaei Khadijeh 
Published: February 2023

Abstract
Objectives
Epidemiologic studies have reported that diet is associated with diabetes and its complications through different pathways. We sought to examine the associations between the Dietary Approaches to Stop Hypertension (DASH) diet and the odds of diabetic nephropathy (DN) developing in Iranian women with existing type 2 diabetes.

Methods
In this case–control study, 105 women with DN and 105 controls, matched for age and diabetes duration, were selected from the Kowsar Diabetes Clinic in Semnan, Iran. DASH, estimated using dietary intake, was assessed using a validated and reliable food frequency questionnaire with 147 items. Anthropometric measurements were assessed for all subjects. Logistic regression was performed to examine the association between DASH and the odds of developing DN.

Results
After controlling for potential confounders, subjects in the highest intake of DASH diet adherence have 84% lower odds of DN, compared to those with the lowest intake (OR = 0.16, 95% CI = 0.07–0.34, P < 0.001). Among DASH diet subcategories, intakes of vegetables (80%), fruits (88%), nuts and legumes (87%), and low-fat dairy (73%) decreased the risk of DN after adjustment for confounders (P < 0.001).

Conclusions
This study showed that the DASH diet is associated with lower odds of DN development in women with type 2 diabetes.
Endured and prevailed: a phenomenological study of doctors’ first year of clinical practice
Authors: Coakley Niamh , O’Leary Paula , Bennett Deirdre 
Published: February 2023

Abstract
Context
The challenging nature of the transition from medical student to doctor is highlighted by the associated negative consequences to new doctors’ mental health and wellbeing. Enhanced understanding of the lived experience of recent medical graduates as they move through the stages of transition over the first year of practice can inform interventions to ease the difficulties encountered.

Methods
Using interpretative phenomenological analysis (IPA), a novel approach to this topic, we explored the lived experience of transition from student to doctor over the first year of practice after graduation. Twelve new graduates were purposively recruited. We conducted semi-structured interviews at the end of their first year of practice with respect to their experience over the first year.

Results
The experience of transition was characterised by overlapping temporal stages. Participants’ initial adjustment period was characterised by shock, coping and stabilisation. A phase of development followed, with growth in confidence and a focus on self-care. Adversity was experienced in the form of interprofessional tensions, overwork, isolation and mistreatment. Finally, a period of reflection and rationalisation marked the end of the first year.

Discussion
Following initial anxiety regarding competence and performance, participants’ experience of transition was predominantly influenced by cultural, relational and contextual aspects of clinical practice. Solutions to ease this challenging time include stage-specific transitional interventions, curricular change at both undergraduate and postgraduate levels and a re-evaluation of the clinical learning environment to mitigate the difficulties endured.
PEEP application during mechanical ventilation contributes to fibrosis in the diaphragm
Authors: Qian Xiaoli , Jiang Ye , Jia Jianwei , Shen Weimin , Ding Yuejia , He Yuhan , Xu Peifeng , Pan Qing , Xu Ying , Ge Huiqing 
Published: February 2023

Abstract
Background
Positive end-expiratory airway pressure (PEEP) is a potent component of management for patients receiving mechanical ventilation (MV). However, PEEP may cause the development of diaphragm remodeling, making it difficult for patients to be weaned from MV. The current study aimed to explore the role of PEEP in VIDD.

Methods
Eighteen adult male New Zealand rabbits were divided into three groups at random: nonventilated animals (the CON group), animals with volume-assist/control mode without/ with PEEP 8 cmH2O (the MV group/ the MV + PEEP group) for 48 h with mechanical ventilation. Ventilator parameters and diaphragm were collected during the experiment for further analysis.

Results
There was no difference among the three groups in arterial blood gas and the diaphragmatic excursion during the experiment. The tidal volume, respiratory rate and minute ventilation were similar in MV + PEEP group and MV group. Airway peak pressure in MV + PEEP group was significantly higher than that in MV group (p < 0.001), and mechanical power was significantly higher (p < 0.001). RNA-seq showed that genes associated with fibrosis were enriched in the MV + PEEP group. This results were further confirmed on mRNA expression. As shown by Masson’s trichrome staining, there was more collagen fiber in the MV + PEEP group than that in the MV group (p = 0.001). Sirius red staining showed more positive staining of total collagen fibers and type I/III fibers in the MV + PEEP group (p = 0.001; p = 0.001). The western blot results also showed upregulation of collagen types 1A1, III, 6A1 and 6A2 in the MV + PEEP group compared to the MV group (p < 0.001, all). Moreover, the positive immunofluorescence of COL III in the MV + PEEP group was more intense (p = 0.003). Furthermore, the expression of TGF-β1, one of the most potent fibrogenic factors, was upregulated at both the mRNA and protein levels in the MV + PEEP group (mRNA: p = 0.03; protein: p = 0.04).

Conclusions
We demonstrated that PEEP application for 48 h in mechanically ventilated rabbits will cause collagen deposition and fibrosis in the diaphragm. Moreover, activation of the TGF-β1 signaling pathway and myofibroblast differentiation may be the potential mechanism of this diaphragmatic fibrosis. These findings might provide novel therapeutic targets for PEEP application-induced diaphragm dysfunction.
Strain evaluation of axially loaded collateral ligaments: a comparison of digital image correlation and strain gauges
Authors: Prusa Gwendolin , Bauer Leandra , Santos Inês , Thorwächter Christoph , Woiczinski Matthias , Kistler Manuel 
Published: February 2023

AbstractThe response of soft tissue to loading can be obtained by strain assessment. Typically, strain can be measured using electrical resistance with strain gauges (SG), or optical sensors based on the digital image correlation (DIC), among others. These sensor systems are already established in other areas of technology. However, sensors have a limited range of applications in medical technology due to various challenges in handling human soft materials. The aim of this study was to compare directly attached foil-type SG and 3D-DIC to determine the strain of axially loaded human ligament structures. Therefore, the medial (MCL) and lateral (LCL) collateral ligaments of 18 human knee joints underwent cyclic displacement-controlled loading at a rate of 20 mm/min in two test trials. In the first trial, strain was recorded with the 3D-DIC system and the reference strain of the testing machine. In the second trial, strain was additionally measured with a directly attached SG. The results of the strain measurement with the 3D-DIC system did not differ significantly from the reference strain in the first trial. The strains assessed in the second trial between reference and SG, as well as between reference and 3D-DIC showed significant differences. This suggests that using an optical system based on the DIC with a given unrestricted view is an effective method to measure the superficial strain of human ligaments. In contrast, directly attached SGs provide only qualitative comparable results. Therefore, their scope on human ligaments is limited to the evaluation of changes under different conditions.
Antiviral therapy inhibited HBV-reactivation and improved long-term outcomes in patients who underwent radiofrequency ablation for HBV-related hepatocellular carcinoma
Authors: Liu Jian , Shen Hao , Huang Shengyu , Lin Jianbo , Yan Zhenlin , Qian Guojun , Lu Zhenghua , Wan Xuying , Zhang Fabiao , Wang Kui , Zhang Yongjie , Li Jun 
Published: February 2023

Abstract
Background
Hepatitis B virus (HBV) reactivation impact negatively the prognosis of patients with HBV-related hepatocellular carcinoma (HCC). This study aimed to observe the effect of antiviral therapy (AVT) on viral reactivation and long-term outcomes after percutaneous radiofrequency ablation (PRFA) for HBV-related HCC.

Methods
Data on 538 patients between 2009 and 2013 were reviewed. Propensity score matching (PSM) analysis was used to adjust for differences in baseline features between patients who received AVT (AVT group) and did not receive it (non-AVT group). Logistic regression was used to identify the independent factors for viral reactivation. The tumor recurrence and overall survival (OS) rates were analyzed using the Kaplan–Meier method. Recurrence patterns were also investigated.

Results
HBV reactivation developed in 10.8% (58/538) of patients after PRFA. AVT was associated independently with decreased viral reactivation (odd ratio: 0.061, 95% confidence interval: 0.018–0.200). In 215 pairs of patients obtained after PSM, the AVT group had lower 1-, 3-, and 5-year recurrence rates (24%, 55%, and 67% vs 33%, 75%, and 85%, respectively) and higher 1-, 3-, and 5-year OS rates (100%, 67%, and 59% vs 100%, 52%, and 42%, respectively) than non-AVT group (P < 0.001 for both). Additionally, the relapses in distant hepatic segments and the late recurrence after 2 years of PRFA were significantly reduced in the AVT group (78/215 vs 111/215 vs., P = 0.001; 39/109 vs. 61/91, P = 0.012, respectively).

Conclusions
AVT reduced late and distal intrahepatic recurrence and improved OS in patients undergoing PRFA for HBV-related HCC by inhibiting viral reactivation.
A large single-center prospective study to investigate the factors influencing the choice of breast-conserving surgery versus mastectomy in Chinese women with early breast cancer
Authors: Li Zhensheng , Liu Yunjiang , Zhang Jing , Li Yue , Du Kaiye , Zhang Shuo , Han Huina , Zhang Jun 
Published: February 2023

Abstract
Background
Compared to mastectomy, breast-conserving surgery (BCS) provides the same survival rate and a higher quality of life for patients with early breast cancer (EBC). However, Chinese women with EBC are known to have a low BCS rate. A large prospective cohort study was conducted to investigate the factors influencing the choice of BCS in this population.

Methods
In 2017, all women with unilateral EBC and eligible for BCS at our institution were enrolled. Before surgery, the patient’s trust in the surgeon and her perceived strength of the surgeon’s recommendation of BCS were measured through an in-person interview and validated ad hoc questionnaire. Multivariate logistic regressions on BCS procedure vs. mastectomy were used to estimate the odds ratio (OR).

Results
One thousand one hundred thirty-six patients enrolled at analysis had an average age of 51.8 and tumor size of 2.4 cm. 19.9% of patients had BCS. The “strong” level of trust in the surgeon was significantly associated with BCS with an OR of 2.944 (p<0.001) when compared to the “average or under” trust. The “strong” and “moderate” strengths in surgeon recommendation for BCS were also found to be significantly associated with the BCS procedure with ORs of 12.376 (p <0.001) and 1.757 (p =0.040), respectively, compared to the “neutral or dissuaded” strength.

Conclusions
Stronger trust in surgeons and BCS recommendation by surgeons are associated with a higher rate of BCS in Chinese women with EBC. Interventional trials are needed to confirm this finding.
Alternation of the gut microbiota in irritable bowel syndrome: an integrated analysis based on multicenter amplicon sequencing data
Authors: Chen Han , Ou Rong , Tang Nana , Su Wei , Yang Ruoyun , Yu Xin , Zhang Guoxin , Jiao Jianhua , Zhou Xiaoying 
Published: February 2023

Abstract
Background
Gut dysbacteriosis has been reported as one of the etiologies for irritable bowel syndrome (IBS). However, the association between gut microbiota and IBS is still inconclusive.

Method
A paired-sample study was designed by retrieving original multicenter 16 s-rRNA data of IBS patients and healthy controls from the GMrepo database. The propensity score matching (PSM) algorithm was applied to reduce confounding bias. The differential analysis of microbiota composition was performed at different taxonomic levels. The co-occurrence network was established. Subgroup analysis was performed to identify specific microbial compositions in different IBS subtypes.

Results
A total of 1522 amplicon samples were initially enrolled. After PSM, 708 individuals (354 IBS and 354 healthy controls) were eligible for further analysis. A total of 1,160 genera were identified. We identified significantly changed taxa in IBS groups (IBS-enriched: the families Enterobacteriaceae, Moraxellaceae and Sphingobacteriaceae; the genera Streptococcus, Bacillus, Enterocloster, Sphingobacterium, Holdemania and Acinetobacter. IBS-depleted: the phyla Firmicutes, Euryarchaeota, Cyanobacteria, Acidobacteria and Lentisphaerae; the families Bifidobacteriaceae, Ruminococcaceae, Methanobacteriaceae and the other 25 families; the genera Faecalibacterium, Bifidobacterium and other 68 genera). The co-occurrence network identified three hub genera and six hub species (including Faecalibacterium prausnitzii) that may be involved in IBS pathophysiology. Strong positive interactions were identified among the Bifidobacterium longum, Bifidobacterium breve and Bifidobacterium adolescentis in the Bifidobacterium community.

Conclusion
This study provides quantitative analysis and visualization of the interaction between the gut microbiota and IBS. The identification of key species should be further validated to evaluate their causal relationships with the pathogenesis of IBS.
Liquid biopsies: the future of cancer early detection
Authors: Connal Siobhan , Cameron James M. , Sala Alexandra , Brennan Paul M. , Palmer David S. , Palmer Joshua D. , Perlow Haley , Baker Matthew J. 
Published: February 2023

AbstractCancer is a worldwide pandemic. The burden it imposes grows steadily on a global scale causing emotional, physical, and financial strains on individuals, families, and health care systems. Despite being the second leading cause of death worldwide, many cancers do not have screening programs and many people with a high risk of developing cancer fail to follow the advised medical screening regime due to the nature of the available screening tests and other challenges with compliance. Moreover, many liquid biopsy strategies being developed for early detection of cancer lack the sensitivity required to detect early-stage cancers. Early detection is key for improved quality of life, survival, and to reduce the financial burden of cancer treatments which are greater at later stage detection. This review examines the current liquid biopsy market, focusing in particular on the strengths and drawbacks of techniques in achieving early cancer detection. We explore the clinical utility of liquid biopsy technologies for the earlier detection of solid cancers, with a focus on how a combination of various spectroscopic and -omic methodologies may pave the way for more efficient cancer diagnostics.
A transdermal treatment with MC903 ameliorates diet-induced obesity by reducing visceral fat and increasing myofiber thickness and energy consumption in mice
Authors: Wada Tsutomu , Miyazawa Yuichiro , Ikurumi Misa , Fuse Kento , Okekawa Akira , Onogi Yasuhiro , Saito Shigeru , Tsuneki Hiroshi , Sasaoka Toshiyasu 
Published: February 2023

Abstract
Aim
MC903 is a synthetic derivative of vitamin D3 that has been designed to diminish its impact on calcium metabolism and is clinically used as a transdermal reagent for psoriasis. Animal studies showed that an oral or intraperitoneal vitamin D3 treatment prevented the development of obesity. In contrast, the bioavailability of orally administered vitamin D3 is reported to be low in obese patients. In the current study, we aimed to investigate the impact of a transdermal treatment with MC903 in established obese mice. We further studied the underlying mechanisms of MC903-mediated metabolic improvement.

Materials and methods
Male C57BL/6 J mice were fed standard chow or a 60% high-fat diet (HFD) for 7 weeks, and a transdermal treatment with MC903 on the ear auricle was initiated thereafter. The metabolic profiles of mice were analyzed during 4 weeks of treatment, and mice were dissected for histological and gene expression analyses. The direct impacts of MC903 and vitamin D3 were investigated using 3T3-L1 adipocytes and C2C12 myotubes in vitro.

Results
HFD-fed mice showed significant increases in body and epididymal white adipose tissue (eWAT) weights with enlarged adipocytes. They exhibited glucose intolerance, decreased oxygen consumption, and chronic inflammation in eWAT. The transdermal treatment with MC903 significantly ameliorated these metabolic abnormalities in HFD-fed mice without affecting food consumption. In accordance with enhanced energy metabolism, myofiber diameters and the expression of uncoupling protein 3 (UCP3) in the gastrocnemius and soleus muscle were significantly increased in MC903-treated HFD mice. In addition, vitamin D3 and MC903 both suppressed adipogenic differentiation and enhanced lipolysis in 3T3-L1 adipocytes, and increased UCP3 expression in cultured C2C12 myotubes. Furthermore, MC903 increased oxygen consumption and UCP3 knockdown significantly decreased them in C2C12 myotubes.

Conclusions
A transdermal treatment with MC903 increased myofiber diameter and energy metabolism and decreased visceral fat accumulation, thereby improving obesity and glucose intolerance in mice.
Diffuse pulmonary meningotheliomatosis with pan-TRK expression by immunohistochemistry: a novel finding and potential pitfall
Authors: Karakas Cansu , Nead Michael A. , Velez Moises J. 
Published: February 2023

Abstract
Background
Pulmonary meningothelial-like nodules (PMNs) are benign proliferations of unclear clinical significance. They are mainly asymptomatic lesions that are usually discovered during the pathologic evaluation of resected pulmonary specimens or following post-mortem examination. Diffuse pulmonary meningotheliomatosis (DPM), which presents as bilateral multiple PMNs throughout the lungs, has been described less frequently. DPMs are benign lesions associated with both neoplastic and non-neoplastic pulmonary conditions.

Case presentation
We report the case of a 59-year-old female patient who presented with a history of cough. Computerized tomography (CT) imaging revealed multiple subcentimeter bilateral pulmonary nodules. transbronchial biopsies were obtained which revealed foci of nodular interstitial proliferations composed of epithelioid to spindled cells in a vague whorled pattern. Immunohistochemical stains were diffusely positive for EMA and progesterone receptor. Furthermore, pan-TRK exhibited strong and diffuse membranous expression in the lesional cells. INSM1 was negative for expression. RNA-based next-generation sequencing for the detection of NTRK fusions was performed and was negative for gene rearrangements involving NTRK1, NTRK2, and NTRK3.

Conclusion
Here, we report a rare case of DPM and report pan-TRK expression in PMNs which has not been described. We provide a brief review of the literature and provide insight into the potential physiologic nature of PMNs. Lastly, we emphasize the recognition of pan-TRK immunoexpression in PMNs to avoid potential diagnostic errors.