bluuebunny/crossref_metadata_2025_split huggingface dataset:
A retrospective and prospective study to establish a preoperative difficulty predicting model for video-assisted thoracoscopic lobectomy and mediastinal lymph node dissection
Authors: Wang Zixiao , Wang Yuhang , Sun Daqiang 
Published: April 2022

Abstract
Background
In previous studies, the difficulty of surgery has rarely been used as a research object. Our study aimed to develop a predictive model to enable preoperative prediction of the technical difficulty of video-assisted thoracoscopic lobectomy and mediastinal lymph node dissection using retrospective data and to validate our findings prospectively.

Methods
Collected data according to the designed data table and took the operation time as the outcome variable. A nomogram to predict the difficulty of surgery was established through Lasso logistic regression. The prospective datasets were analyzed and the outcome was the operation time.

Results
This retrospective study enrolled 351 patients and 85 patients were included in the prospective datasets. The variables in the retrospective research were selected by Lasso logistic regression (only used for modeling and not screening), and four significantly related influencing factors were obtained: FEV1/FVC (forced expiratory volume in the first second/forced vital capacity) (p < 0.001, OR, odds ratio = 0.89, 95% CI, confidence interval = 0.84–0.94), FEV1/pred FEV1 (forced expiratory volume in the first second/forced expiratory volume in the first second in predicted) (p = 0.076, OR = 0.98, 95% CI = 0.95–1.00), history of lung disease (p = 0.027, OR = 4.00, 95% CI = 1.27–15.64), and mediastinal lymph node enlargement or calcification (p < 0.001, OR = 9.78, 95% CI = 5.10–19.69). We used ROC (receiver operating characteristic) curves to evaluate the model. The training set AUC (area under curve) value was 0.877, the test set’s AUC was 0.789, and the model had a good calibration curve. In a prospective study, the data obtained in the research cohort were brought into the model again for verification, and the AUC value was 0.772.

Conclusion
Our retrospective study identified four preoperative variables that are correlated with a longer surgical time and can be presumed to reflect more difficult surgical procedures. Our prospective study verified that the variables in the prediction model (including prior lung disease, FEV1/pred FEV1, FEV1/FVC, mediastinal lymph node enlargement or calcification) were related to the difficulty.
Risk factors for periappendiceal adhesions in acute appendicitis: a retrospective comparative study
Authors: Gao Shenshuo , Guo Xiaobo , Li Leping , Jing Changqing , Ma Yan 
Published: April 2022

Abstract
Purpose
Acute appendicitis usually requires immediate surgical treatment, but appendectomies were difficult for some patients with severe periappendiceal adhesions. We investigated risk factors of intraoperative adhesions to help surgeons make better treatment plans for appendicitis.

Methods
We retrospectively analyzed 186 cases diagnosed with acute appendicitis and underwent surgery in Shandong Provincial Hospital affiliated to Shandong First Medical University between January 2018 and December 2019. According to the degree of intraoperative adhesions, they were divided into mild, moderate and severe groups. Then, we analyzed a number of preoperative factors contributed to adhesions, suppuration and perforation during appendectomy in 186 patients.

Results
Contrast to the moderate group (MoG) and the mild group (MiG), the severe degree of adhesions group (SG) had a higher intraoperative perforation and suppuration rate, a greater likelihood of conversion to open and more postoperative complications. Multivariable logistic regression analysis showed that recurrent appendicitis and high neutrophil percentage were independently associated with periappendiceal adhesions. The preoperative ultrasonography (US) revealed periappendiceal fluid and high neutrophil percentage were independently associated with appendix suppuration. A high preoperative neutrophil percentage was independently associated with appendix perforation.

Conclusions
Recurrent appendicitis and preoperative high neutrophil percentage were risk factors of periappendiceal adhesions; preoperative US revealed periappendiceal fluid and high neutrophil percentage were risk factors of appendix suppuration; and a high preoperative neutrophil percentage was a risk factor of appendix perforation.
Impact of temperature changes to the adhesion strength of molar tubes: an in vitro study
Authors: Palesik Benedikta , Šileikytė Kotryna , Griškevičius Julius , Stonkus Rimantas , Šidlauskas Antanas , Lopatienė Kristina 
Published: April 2022

Abstract
Background
The main purpose of this was to determine study adhesion strength of molar tubes bonding with a composite adhesive after exposure to a sudden change in temperature (thermal cycles).

Methods
The study sample consisted of 40 recently extracted human first permanent molars, which were randomly divided into two groups of 20: group 1 was the experimental group (affected by thermal cycles), and group 2 was the control group. Molar tubes were bonded with a light-cure tube adhesive. The experimental group teeth were dipped 2,000 times in saline at 5 °C and at 55 °C. The control group were immersed in 37 °C saline. Molar tubes for both groups were removed with an adapted Mecmesim Multitesters 2.5—I, and the data were recorded with EMPEROR software. ANOVA was used to calculate and compare the results.

Results
In the experimental group of the teeth, the maximum force was obtained at 94.2 N and the lowest force was 19.69 N. In the control group of the teeth, the maximum force was obtained at 159.1 N and the lowest force was 28.1 N. In the experimental group, the mean debonding force (59.12 N) was statically significantly smaller than in the control group (79.88 N), p = 0.0345. The forces in the control group were by 1.35 times greater than those in the experimental group.

Conclusions
The forces of the adhesion of molar tubes to the tooth surface were reduced after exposure to a sudden change in temperature (thermal cycles). The results were significantly different between the experimental group and the control group.
Suspension of face-to-face teaching and ad hoc transition to digital learning under Covid-19 conditions – a qualitative study among dental students and lecturers
Authors: Hertrampf Katrin , Wenz Hans-Jürgen , Kaduszkiewicz Hanna , Goetz Katja 
Published: April 2022

Abstract
Background
In mid-March 2020, the coronavirus pandemic led to a national lockdown in Germany. Face-to-face teaching was cancelled in universities for the 2020 summer semester. Teaching moved online with no prior IT testing and lecturer training. The study analyses experiences of the suspension of face-to-face teaching and the move to digitalised learning for students and lecturers of dentistry at Kiel.

Methods
In summer 2020, qualitative guided interviews were conducted with students (4th, 6th, 8th, and 10th semesters), and lecturers. Deductive and inductive qualitative content analysis of the results was carried out.

Results
Thirty-nine students (69% female) and 19 lecturers (32% female) were interviewed. Reactions to the changes in teaching were observed. Feelings ranged from an essentially positive attitude, through insecurity and uncertainty to a failure to fully appreciate the situation. The loss of social contact was lamented. Digitalisation was associated with technological challenges and additional work. However, it also fostered learning independent of time and place, and encouraged autonomy. Negative aspects of digitalisation included a lack of feedback and loss of interaction.

Conclusion
The introduction of ad hoc digitalisation challenged both students and lecturers alike. Dealing with lockdown and the changes in teaching and studying required significant flexibility.
CRISPR-mediated Bmpr2 point mutation exacerbates late pulmonary vasculopathy and reduces survival in rats with experimental pulmonary hypertension
Authors: Kabwe Jane Chanda , Sawada Hirofumi , Mitani Yoshihide , Oshita Hironori , Tsuboya Naoki , Zhang Erquan , Maruyama Junko , Miyasaka Yoshiki , Ko Hideyoshi , Oya Kazunobu , Ito Hiromasa , Yodoya Noriko , Otsuki Shoichiro , Ohashi Hiroyuki , Okamoto Ryuji , Dohi Kaoru , Nishimura Yuhei , Mashimo Tomoji , Hirayama Masahiro , Maruyama Kazuo 
Published: April 2022

Abstract
Background
Patients with pulmonary arterial hypertension (PAH) carrying bone morphogenetic protein receptor type 2 (Bmpr2) mutations present earlier with severe hemodynamic compromise and have poorer survival outcomes than those without mutation. The mechanism underlying the worsening clinical phenotype of PAH with Bmpr2 mutations has been largely unaddressed in rat models of pulmonary hypertension (PH) because of the difficulty in reproducing progressive PH in mice and genetic modification in rats. We tested whether a clinically-relevant Bmpr2 mutation affects the progressive features of monocrotaline (MCT) induced-PH in rats.

Methods
A monoallelic single nucleotide insertion in exon 1 of Bmpr2 (+/44insG) was generated in rats using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9, then PH, pulmonary vascular disease (PVD) and survival after MCT injection with or without a phosphodiesterase type 5 inhibitor, tadalafil, administration were assessed.

Results
The +/44insG rats had reduced BMPR2 signalling in the lungs compared with wild-type. PH and PVD assessed at 3-weeks after MCT injection were similar in wild-type and +/44insG rats. However, survival at 4-weeks after MCT injection was significantly reduced in +/44insG rats. Among the rats surviving at 4-weeks after MCT administration, +/44insG rats had increased weight ratio of right ventricle to left ventricle plus septum (RV/[LV + S]) and % medial wall thickness (MWT) in pulmonary arteries (PAs). Immunohistochemical analysis showed increased vessels with Ki67-positive cells in the lungs, decreased mature and increased immature smooth muscle cell phenotype markers in the PAs in +/44insG rats compared with wild-type at 3-weeks after MCT injection. Contraction of PA in response to prostaglandin-F2α and endothelin-1 were significantly reduced in the +/44insG rats. The +/44insG rats that had received tadalafil had a worse survival with a significant increase in RV/(LV + S), %MWT in distal PAs and RV myocardial fibrosis compared with wild-type.

Conclusions
The present study demonstrates that the Bmpr2 mutation promotes dedifferentiation of PA smooth muscle cells, late PVD and RV myocardial fibrosis and adversely impacts both the natural and post-treatment courses of MCT-PH in rats with significant effects only in the late stages and warrants preclinical studies using this new genetic model to optimize treatment outcomes of heritable PAH.
Survival and prognostic factors in patients undergoing pulmonary metastasectomy for lung metastases from retroperitoneal sarcoma
Authors: Takatsu Fumiaki , Yamamoto Hiromasa , Tomioka Yasuaki , Tanaka Shin , Shien Kazuhiko , Suzawa Ken , Miyoshi Kentaroh , Otani Shinji , Okazaki Mikio , Sugimoto Seiichiro , Yamane Masaomi , Takahashi Katsuhito , Toyooka Shinichi 
Published: April 2022

Abstract
Background
Soft-tissue sarcomas are rare malignancies that consist of many different histologic subtypes and arise in various locations in the body. In patients with lung metastases from retroperitoneal sarcomas, the long-term outcomes and prognostic factors are unknown. This study is a retrospective review of patients undergoing pulmonary metastasectomy for retroperitoneal sarcoma metastases at one institution, with the purpose of determining prognostic factors and clinical outcomes.

Methods
This is a single-center, retrospective cohort study of patients undergoing pulmonary metastasectomy for lung metastases from various sarcomas at Okayama University Hospital from January 2006 to December 2018. The Kaplan-Meier method and log-rank test were used for the analyses, and cut-off values of continuous variables were determined by a receiver operating characteristic curve analysis.

Results
Twenty-four patients underwent the first pulmonary metastasectomy for lung metastases from retroperitoneal sarcoma in our hospital. Leiomyosarcoma was the most common histologic subtype of retroperitoneal sarcoma (79.2%, n = 19). Median overall survival was 49.9 months, and the 3-year and 5-year survival rates after the first pulmonary metastasectomy were 62.5% and 26.4% respectively. In univariate analysis, age ≥56 years, disease-free interval < 15 months, and size of metastasis (≥ 27 mm) were associated with poor survival.

Conclusion
Pulmonary metastasectomy can be considered as an effective management strategy in retroperitoneal sarcoma patients with lung metastases in appropriately selected cases, just as it is for other sarcomas.
TET1 mutations as a predictive biomarker for immune checkpoint inhibitors in colon adenocarcinoma
Authors: Qiu Tianzhu , Wang Xiaoxuan , Du Furong , Hu Xiangjing , Sun Fujun , Song Chao , Zhao Jie 
Published: April 2022

Abstract
Background
The ten-eleven translocation 1 (TET1), which is essential for active DNA demethylation, plays a multifaceted role in the pathogenesis of colorectal cancer. The study has demonstrated the association of TET1 mutations with a high response to immune checkpoint inhibitors (ICIs) in diverse cancers. However, the relationship between TET1 mutations and the response to ICIs in colon cancer is still lacking.

Methods
The prognosis, predictive markers, immune characteristics, mutation number of DNA damage repair (DDR) pathways, pathway enrichment, and drug sensitivity conditions were all compared between TET1-mutated and wild-type patients with colon adenocarcinoma (COAD).

Results
The overall survival of patients with TET1 mutations in the ICI-treated cohort was significantly longer than those without (p = 0.0059). Compared with the wild-type patients, TET1-mutated patients had higher tumor mutational burden and neoantigen load, enhanced abundance of tumor-infiltrating immune cells, increased expression of immune-related genes, and mutation number of DDR pathways. Additionally, the patients with TET1 mutations were found to be more sensitive to lapatinib and 5-fluorouracil.

Conclusion
These findings suggest that TET1 mutations may serve as a potential biomarker for the response to ICIs in COAD patients.
A proteolysis-targeting chimera molecule selectively degrades ENL and inhibits malignant gene expression and tumor growth
Authors: Li Xin , Yao Yuan , Wu Fangrui , Song Yongcheng 
Published: April 2022

Abstract
Background
Chromosome translocations involving mixed lineage leukemia 1 (MLL1) cause acute leukemia in most infants and 5–10% children/adults with dismal clinical outcomes. Most frequent MLL1-fusion partners AF4/AFF4, AF9/ENL and ELL, together with CDK9/cyclin-T1, constitute super elongation complexes (SEC), which promote aberrant gene transcription, oncogenesis and maintenance of MLL1-rearranged (MLL1-r) leukemia. Notably, ENL, but not its paralog AF9, is essential for MLL1-r leukemia (and several other cancers) and therefore a drug target. Moreover, recurrent ENL mutations are found in Wilms tumor, the most common pediatric kidney cancer, and play critical roles in oncogenesis.

Methods
Proteolysis-Targeting Chimera (PROTAC) molecules were designed and synthesized to degrade ENL. Biological activities of these compounds were characterized in cell and mouse models of MLL1-r leukemia and other cancers.

Results
Compound 1 efficiently degraded ENL with DC50 of 37 nM and almost depleted it at ~ 500 nM in blood and solid tumor cells. AF9 (as well as other proteins in SEC) was not significantly decreased. Compound 1-mediated ENL reduction significantly suppressed malignant gene signatures, selectively inhibited cell proliferation of MLL1-r leukemia and Myc-driven cancer cells with EC50s as low as 320 nM, and induced cell differentiation and apoptosis. It exhibited significant antitumor activity in a mouse model of MLL1-r leukemia. Compound 1 can also degrade a mutant ENL in Wilms tumor and suppress its mediated gene transcription.

Conclusion
Compound 1 is a novel chemical probe for cellular and in vivo studies of ENL (including its oncogenic mutants) and a lead compound for further anticancer drug development.
EXpert consensus On Diaphragm UltraSonography in the critically ill (EXODUS): a Delphi consensus statement on the measurement of diaphragm ultrasound-derived parameters in a critical care setting
Authors: Haaksma Mark E. , Smit Jasper M. , Boussuges Alain , Demoule Alexandre , Dres Martin , Ferrari Giovanni , Formenti Paolo , Goligher Ewan C. , Heunks Leo , Lim Endry H. T. , Mokkink Lidwine B. , Soilemezi Eleni , Shi Zhonghua , Umbrello Michele , Vetrugno Luigi , Vivier Emmanuel , Xu Lei , Zambon Massimo , Tuinman Pieter R. 
Published: April 2022

Abstract
Background
Diaphragm ultrasonography is rapidly evolving in both critical care and research. Nevertheless, methodologically robust guidelines on its methodology and acquiring expertise do not, or only partially, exist. Therefore, we set out to provide consensus-based statements towards a universal measurement protocol for diaphragm ultrasonography and establish key areas for research.

Methods
To formulate a robust expert consensus statement, between November 2020 and May 2021, a two-round, anonymous and online survey-based Delphi study among experts in the field was performed. Based on the literature review, the following domains were chosen: “Anatomy and physiology”, “Transducer Settings”, “Ventilator Impact”, “Learning and expertise”, “Daily practice” and “Future directions”. Agreement of ≥ 68% (≥ 10 panelists) was needed to reach consensus on a question.

Results
Of 18 panelists invited, 14 agreed to participate in the survey. After two rounds, the survey included 117 questions of which 42 questions were designed to collect arguments and opinions and 75 questions aimed at reaching consensus. Of these, 46 (61%) consensus was reached. In both rounds, the response rate was 100%. Among others, there was agreement on measuring thickness between the pleura and peritoneum, using > 10% decrease in thickness as cut-off for atrophy and using 40 examinations as minimum training to use diaphragm ultrasonography in clinical practice. In addition, key areas for research were established.

Conclusion
This expert consensus statement presents the first set of consensus-based statements on diaphragm ultrasonography methodology. They serve to ensure high-quality and homogenous measurements in daily clinical practice and in research. In addition, important gaps in current knowledge and thereby key areas for research are established.
Trial registration The study was pre-registered on the Open Science Framework with registration digital object identifier https://doi.org/10.17605/OSF.IO/HM8UG.
SETDB1 interactions with PELP1 contributes to breast cancer endocrine therapy resistance
Authors: Liu Zexuan , Liu Junhao , Ebrahimi Behnam , Pratap Uday P. , He Yi , Altwegg Kristin A. , Tang Weiwei , Li Xiaonan , Lai Zhao , Chen Yidong , Shen Liangfang , Sareddy Gangadhara R. , Viswanadhapalli Suryavathi , Tekmal Rajeshwar R. , Rao Manjeet K. , Vadlamudi Ratna K. 
Published: April 2022

Abstract
Background
Methyltransferase SETDB1 is highly expressed in breast cancer (BC), however, the mechanisms by which SETDB1 promotes BC progression to endocrine therapy resistance remains elusive. In this study, we examined the mechanisms by which SETDB1 contribute to BC endocrine therapy resistance.

Methods
We utilized therapy sensitive (MCF7 and ZR75), therapy resistant (MCF7-TamR, MCF7-FR, MCF7-PELP1cyto, MCF7-SETDB1) estrogen receptor alpha positive (ER+)BC models and conducted in vitro cell viability, colony formation, 3-dimensional cell growth assays to investigate the role of SETDB1 in endocrine resistance. RNA-seq of parental and SETDB1 knock down ER+ BC cells was used to identify unique pathways. SETDB1 interaction with PELP1 was identified by yeast-two hybrid screen and confirmed by immunoprecipitation and GST-pull down assays. Mechanistic studies were conducted using Western blotting, reporter gene assays, RT-qPCR, and in vitro methylation assays. Xenograft assays were used to establish the role of PELP1 in SETDB1 mediated BC progression.

Results
RNA-seq analyses showed that SETDB1 regulates expression of a subset of estrogen receptor (ER) and Akt target genes that contribute to endocrine therapy resistance. Importantly, using yeast-two hybrid screen, we identified ER coregulator PELP1 as a novel interacting protein of SETDB1. Biochemical analyses confirmed SETDB1 and PELP1 interactions in multiple BC cells. Mechanistic studies confirmed that PELP1 is necessary for SETDB1 mediated Akt methylation and phosphorylation. Further, SETDB1 overexpression promotes tamoxifen resistance in BC cells, and PELP1 knockdown abolished these effects. Using xenograft model, we provided genetic evidence that PELP1 is essential for SETDB1 mediated BC progression in vivo. Analyses of TCGA datasets revealed SETDB1 expression is positively correlated with PELP1 expression in ER+ BC patients.

Conclusions
This study suggests that the PELP1/SETDB1 axis play an important role in aberrant Akt activation and serves as a novel target for treating endocrine therapy resistance in breast cancer.
Role of the radiologist in the diagnosis and management of the two forms of hepatic echinococcosis
Authors: Calame Paul , Weck Mathieu , Busse-Cote Andreas , Brumpt Eleonore , Richou Carine , Turco Celia , Doussot Alexandre , Bresson-Hadni Solange , Delabrousse Eric 
Published: April 2022

AbstractEchinococcosis is a parasitic disease caused by two zoonotic tapeworms (cestodes) of the Echinocococcus genus. It can be classified as either alveolar or cystic echinococcosis. Although the two forms differ significantly in terms of imaging findings, they share similarities in terms of management and treatment. In parallel to medical treatment with albendazole (ABZ), and surgery, historically used in these diseases, various imaging-guided interventional procedures have recently emerged (drainage, stenting, or Puncture, aspiration, injection, and reaspiration (PAIR)). These options open up a new range of therapeutic options. As in oncology, multidisciplinary consultation meetings now play a major role in adapted management and patient care in hepatic echinococcosis. Consequently, diagnostic imaging and interventional expertise have brought radiologists to the fore as important members of these multidisciplinary team. The radiologist will need to evaluate parasite activity in both forms of the disease, to guide the choice of the appropriate therapy from among medical treatment, interventional radiology procedures and/or surgical treatment. Knowledge of the specific complications of the two forms of echinococcosis will also help radiologists to discuss the appropriate treatment and management. The aim of this review is to describe the core knowledge that what a radiologist should possess to actively participate in multidisciplinary meetings about hepatic echinococcosis. We discuss the role of imaging, from diagnosis to treatment, in alveolar (AE) and cystic echinococcosis (CE), respectively.