bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multidisciplinary treatment of retroperitoneal ectopic pregnancy: a case report and literature review
Authors: Xu Hainan , Cheng Dali , Yang Qing , Wang Dandan 
Published: June 2022

Abstract
Background
Retroperitoneal ectopic pregnancy (REP) is an extremely rare type of ectopic pregnancy, with a total of less than 32 cases reported in the English literature. Early diagnosis of REP is very difficult and all treatments entail a high risk of life-threatening complications.

Case presentation
A 29-year-old nulliparous woman presented a history of 50-day amenorrhea and 7-day upper abdominal pain without vaginal spotting. The serum beta-human chorionic gonadotropin (β-hCG) value was 65,004 m-international units per milliliter (mIU/mL), but no intrauterine gestational sac was found via transvaginal sonography (TVS). Then transabdominal ultrasonography (TAS) and abdominal contrast-enhanced computer tomography (CT) identified a retroperitoneal ectopic pregnancy (REP) tightly adjacent to the inferior vena cava and the abdominal aorta. After consultation from a multidisciplinary team, systemic methotrexate (MTX, intramuscular 20 mg daily for 5 consecutive days) combined with ultrasound-guided local potassium chloride solution injection into the gestational sac was scheduled firstly for the patient. However, serum β-hCG continued to increase and the patient experienced worsening abdominal pain. Laparotomy was performed jointly by a gynecologist and a vascular surgeon. During the operation, the gestational sac with fetal bud measuring about 4.5 × 4.0x3.0 cm, tightly adherent to the surface of inferior vena cava and the left side of abdominal aorta, was carefully dissociated out from the surrounding tissues and removed en bloc. Histopathology examination confirmed the diagnosis of REP. The patient recovered uneventfully and her serum β-hCG returned to normal range on the 23th postoperative day.

Conclusions
Considering the possibility of REP and combined radiological examinations, such as ultrasonography and CT, are crucial for the early diagnosis of this rare condition. A multidisciplinary team is necessary to treat REP.
T-DM1 efficacy in trastuzumab-pertuzumab pre-treated HER2 positive metastatic breast cancer patients: a meta-analysis
Authors: Omarini Claudia , Piacentini Federico , Sperduti Isabella , Cerma Krisida , Barbolini Monica , Canino Fabio , Nasso Cecilia , Isca Christel , Caggia Federica , Dominici Massimo , Moscetti Luca 
Published: June 2022

Abstract
Background
Current guidelines consider T-DM1 the standard 2nd line therapy for HER2 positive metastatic breast cancer (MBC) patients following trastuzumab (T) + pertuzumab (P) and taxane 1st line treatment. Despite this, there are no prospective studies supporting this sequence.

Methods
We performed a meta-analysis using real world data to determine the efficacy of T-DM1 after 1st line TP in HER2 positive MBC patients. We used a random-effect model to find differences in the rate of 1-year progression free survival (PFS) between TP pre-treated population and the EMILIA phase III pivotal trial.

Results
Seven studies were eligible. The meta-analysis showed a combined 1-year PFS risk difference for T-DM1 efficacy after TP in 2nd or more lines of -0.122, with lower and upper limits of -0.253 and 0.010, respectively (p = 0.07), with low heterogeneity among studies (I2 0.01%, p = 0.836). Considering the four studies on T-DM1 in 2nd line setting, 1-year PFS risk was -0.034 (95% CI -0.207 – 0,139; p = 0.701) (I2 0.01%, p = 0.91).

Conclusion
Overall, the efficacy of T-DM1 after TP seems to be similar to that previously reported in the EMILIA trial. In the second line setting, data are not mature enough to confirm T-DM1 efficacy in TP pre-treated population.
Potential prognosis index for m6A-related mRNA in cholangiocarcinoma
Authors: Zhu Huaqiang , Zhao Haini , Wang Jianlu , Zhao Shuchao , Ma Chaoqun , Wang Dongliang , Gao Hengjun , Yang Faji , Ni Qingqiang , Li Hongguang , Zhou Xu , Zhang Chunqing , Lu Jun 
Published: June 2022

Abstract
Background
Cholangiocarcinoma (CHOL) is a malignant tumor that originates in the extrahepatic bile duct and can extend from the hilar region to the lower end of the common bile duct. The prognosis of CHOL patients is particularly poor; therefore, in this study, we screened mRNAs correlated with N6-methyladenosine (m6A) to construct a risk model for prognosis in CHOL.

Methods
The TCGA-CHOL dataset was applied to obtain and analyze the coexpression of 1281 m6A-related mRNAs, from which 14 were selected for further analysis through univariate proportional hazards (cox) regression analysis. Aryl hydrocarbon receptor interacting protein (AIP), CCAAT/enhancer binding protein beta (CEBPB), syndecan1 (SDC1), vacuolar protein sorting 25 homolog (VPS25) and syntaxin binding protein 2 (STXBP2) were then screened out through the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis to develop a precise m6A-related mRNA prognosis risk model (MRMRPM) with an area under curve (AUC) of 0.908 and 0.923 after 1 and 2 years, respectively. We divided the samples into high-risk and low-risk groups using the m6A-related mRNA prognosis risk model.

Results
Kaplan–Meier analysis indicated poor overall survival (OS) for the high-risk group. Two Gene Expression Omnibus (GEO) datasets (GSE89748 and GSE107943) were used to validate the risk model. The results of drug sensitivity and immune cell infiltration analysis showed that the risk model could serve as a prognosis index of potential immunotherapeutic characteristics and drug sensitivity. Furthermore, the proportion of resting dendritic cells and regulatory T cells was positively associated with an increased expression of four m6A-related mRNAs — AIP, CEBPB, SDC1, and VPS25 — in the high-risk CHOL group.

Conclusions
Our findings suggest that this model can be a prognostic indicator for CHOL patients.
Suboptimal use of hormonal therapy among German men with localized high-risk prostate Cancer during 2005 to 2015: analysis of registry data
Authors: Abera Semaw Ferede , Bedir Ahmed , Glowka André , Vordermark Dirk , Medenwald Daniel 
Published: June 2022

Abstract
Background
This study assesses the use of hormonal therapy to treat high-risk localized prostate cancer (HRLPCa) cases diagnosed between 2005 and 2015.

Methods
All N0-XM0 with ≥T3a, or PCa cases with poorly differentiated feature (equivalent to Gleason score ≥ 8), diagnosed between 2005 and 2015 were extracted from German population-based cancer registries. Cases treated by surgery or chemotherapy were excluded. Description of hormonal therapy use by HRLPCa cases’ profile was presented. Relative risk (RR) was computed with a log-link function to identify factors associated with hormonal therapy use among radiotherapy-treated HRLPCa cases.

Results
A total of 5361 HRLPCa cases were analyzed. Only 27.6% (95% confidence interval [CI]: 26.4–28.8%) of the HRLPCa cases received hormonal therapy in combination with radiotherapy. The use of combined hormonal therapy and radiotherapy varied from 19.8% in Saxony to 47.8% in Schleswig-Holstein.
Application of hormonal therapy was higher for the locally advanced cases compared to the poorly differentiated cases (relative risk [RR] = 1.28; 95%CI: 1.19, 1.37). Older patients showed a slightly increased use of hormonal therapy (RR for a 10-year age increase = 1.09; 95%CI: 1.02, 1.16). Compared to PCa cases from the most affluent residential areas, cases from the least affluent (RR = 0.71; 95%CI: 0.55, 0.92) and medium (RR = 0.75; 95%CI: 0.58, 0.96) areas had decreased use of hormonal therapy. The introduction of the German S3-guideline did not make a marked difference in the uptake of both hormonal therapy and radiotherapy (RR = 1.02; 95%CI: 0.95, 1.09).

Conclusion
This study found a low use of hormonal therapy among HRLPCa patients treated without surgery. The introduction of the German S3-guideline for prostate cancer treatment does not seem to have impacted hormonal therapy use.
An iron metabolism and immune related gene signature for the prediction of clinical outcome and molecular characteristics of triple-negative breast cancer
Authors: Li Xiao-Fen , Fu Wen-Fen , Zhang Jie , Song Chuan-Gui 
Published: June 2022

Abstract
Background
An imbalance of intracellular iron metabolism can lead to the occurrence of ferroptosis. Ferroptosis can be a factor in the remodeling of the immune microenvironment and can affect the efficacy of cancer immunotherapy. How to combine ferroptosis-promoting modalities with immunotherapy to suppress triple-negative breast cancer (TNBC) has become an issue of great interest in cancer therapy. However, potential biomarkers related to iron metabolism and immune regulation in TNBC remain poorly understand.

Methods
We constructed an optimal prognostic TNBC-IMRGs (iron metabolism and immune-related genes) signature using least absolute shrinkage and selection operator (LASSO) cox regression. Survival analysis and ROC curves were analyzed to identify the predictive value in a training cohort and external validation cohorts. The correlations of gene signature with ferroptosis regulators and immune infiltration are also discussed. Finally, we combined the gene signature with the clinical model to construct a combined model, which was further evaluated using a calibration curve and decision curve analysis (DCA).

Results
Compared with the high-risk group, TNBC patients with low-risk scores had a remarkably better prognosis in both the training set and external validation sets. Both the IMRGs signature and combined model had a high predictive capacity, 1/3/5- year AUC: 0.866, 0.869, 0.754, and 1/3/5-yaer AUC: 0.942, 0.934, 0.846, respectively. The calibration curve and DCA also indicate a good predictive performance of the combined model. Gene set enrichment analysis (GSEA) suggests that the high-risk group is mainly enriched in metabolic processes, while the low-risk group is mostly clustered in immune related pathways. Multiple algorithms and single sample GSEA further show that the low-risk score is associated with a high tumor immune infiltration level. Differences in expression of ferroptosis regulators are also observed among different risk groups.

Conclusions
The IMRGs signature based on a combination of iron metabolism and immune factors may contribute to evaluating prognosis, understanding molecular characteristics and selecting treatment options in TNBC.
Rationale and design of ON-TRK: a novel prospective non-interventional study in patients with TRK fusion cancer treated with larotrectinib
Authors: Yang James C. H. , Brose Marcia S. , Castro Gilberto , Kim Edward S. , Lassen Ulrik N. , Leyvraz Serge , Pappo Alberto , López-Ríos Fernando , Reeves John A. , Fellous Marc , Penault-Llorca Frédérique , Rudzinski Erin R. , Tabatabai Ghazaleh , Vassal Gilles , Drilon Alexander , Trent Jonathan 
Published: June 2022

AbstractBackgroundTropomyosin receptor kinase (TRK) fusion proteins resulting from neurotrophic tyrosine receptor kinase (NTRK) gene fusions are rare primary oncogenic drivers in a wide array of tumors. Larotrectinib is a first-in-class, highly selective, central nervous system-active TRK inhibitor approved by the US Food and Drug Administration (FDA), European Medicines Agency (EMA), and over 40 countries for the treatment of TRK fusion solid tumors in adult and pediatric patients. Due to the rarity of TRK fusion cancer, larotrectinib was granted accelerated approval based on a relatively small number of patients enrolled in three early phase trials. ON-TRK aims to evaluate the safety profile of larotrectinib in a broader population and over extended time periods.MethodsON-TRK is a prospective, non-interventional, open-label, multicenter, multi-cohort, post-approval study in adult and pediatric patients with locally advanced or metastatic TRK fusion cancer treated with larotrectinib that will describe the safety and effectiveness of larotrectinib in real-world practice conditions. Adult patients will be grouped by tumor type and followed for at least 2 years. Patients < 18 years old will be enrolled under a ‘pediatric’ cohort regardless of tumor type and will be followed for 5 years to evaluate the risk of potential long-term adverse effects of larotrectinib on their growth and development. The effectiveness of larotrectinib in the overall study population as well as in patient subgroups will also be evaluated. Procedures avoided in patients with infantile fibrosarcoma (e.g., amputation) and the number of patients who were able to undergo surgery with a curative intent (excluding amputation) because of the use of larotrectinib will be described. Larotrectinib treatment patterns in real-world practice, including dosing and duration of treatment, will be described.DiscussionThe FDA Accelerated Approval Program allows for earlier approval of and patient access to drugs that treat serious conditions and fill an unmet medical need. This study is designed to fulfill post-approval requirements set by the FDA as well as post-marketing requirements set forth by local regulatory bodies and is part of the risk management plan for the EMA.Study registrationThis study is registered at ClinicalTrials.gov (NCT04142437).Protocol versionv2.5, 25 March 2021.
Predictors for elevation of Intraocular Pressure (IOP) on glaucoma patients; a retrospective cohort study design
Authors: Birhanu Getasew , Tegegne Awoke Seyoum 
Published: June 2022

Abstract
Objective
Because of the increase in the number of cases, currently, glaucoma is a significant public health issue that it leads to optic nerve damage and vision loss. High Intraocular Pressure reading indicates that the treatment given to a glaucoma patient is not sufficient/ adequate. Hence, the elevation of intraocular pressure is one of the indicators that, the therapy given to glaucoma patients under treatment is inadequate. Therefore, the main objective of the current study was to investigate predictors for the variation of elevation of IOP readings on glaucoma patients.

Materials and methods
A retrospective cohort study design was conducted on 1254 glaucoma patients, whose followed-ups were from September 2015 to August 2016 at Felege Hiwot Teaching and Specialized Hospital, North West Ethiopia. Data analysis was conducted using Statistical Analysis of Systems (SAS) software version 9.2 and AMOS software. The parameter estimation was conducted using the maximum likelihood estimation technique.

Results
Main effects like age (β = 0.01, t-value = 0.15, p-value = 0.018), patients with normal blood pressure (β = -3.35, t-value = -2.28, p-value = 0.0263), patients without diabetics (β = -3.79, t-value = -2.47, p-value = 0.014), visiting times (β = -6.00, t-value = -5.02, p-value = 0.0001), farmer glaucoma patients (β = -6.04, t-value = 3.87, p-value = 0.0001) had significant and indirect effect for the variation of elevation of IOP on glaucoma patients. Interaction effects like visiting time with existence of diabetes, visiting time with cataract surgery significantly effected on the variable of interest. Hence, both main and interaction effects had significant effects on the variable of interest.
This study had identified socio-demographic characteristics, personal/individual behaviors, and clinical factors for the variation of elevation of IOP. The findings, in the current investigation, help health staff to conduct health-related education for awareness creation. Health-related education, about the progression of glaucoma, should be conducted on patients.
Study protocol for a randomized controlled trial of the NEIVATECH virtual reality system to improve visual function in children with anisometropic amblyopia
Authors: Leal Vega L. , Piñero D. P. , Hernández Rodríguez C. J. , Molina Martín A. , Morales-Quezada L. , Vallelado Álvarez A. I. , Arenillas Lara J. F. , Coco Martín M. B. 
Published: June 2022

AbstractBackgroundInterest in developing alternative methods for the treatment of amblyopia has long been a topic of interest among clinicians and researchers, as prescribed occlusion and penalization therapies do not always provide an effective response and are associated with a high risk of recurrence and non-compliance. Here, we present the protocol of a small-scale RCT to evaluate the safety and clinical efficacy of a novel VR-based system designed to provide binocular vision training to children with anisometropic amblyopia.MethodsWe aim to recruit a total of 60 children with anisometropic amblyopia aged 5-17 years with no previous treatment for amblyopia other than refractive correction from the pediatric ophthalmology units of the University Clinical Hospital of Valladolid and the Vithas Medimar International Hospital of Alicante. Children who meet the eligibility criteria and consent to participate will be randomly assigned to a three-month intervention group of 18 half-hour in-office therapy sessions with the NEIVATECH system (group A) or to a parallel group receiving 2 hours of conventional patching per day at home for the same period of time (group B). Assessments of visual function will be carried out before the intervention and at 1, 2 and 3 months, with changes in distance BCVA being the primary outcome measure to be considered. Patient safety, compliance, satisfaction and acceptance to treatment will also be assessed after therapy as other valuable outcome measures. In addition, a rsfMRI scan will be performed on a subgroup of 5 patients from each group at the pre-intervention visit and at the post-intervention visit to test the effects of both therapies on neural plasticity in the visual cortex.DiscussionThe NEIVATECH system has been conceived as a serious game designed to provide binocular vision training to anisometropic amblyopic children by complementing the concepts of perceptual learning, dichoptic training and gamification in an immersive VR environment. We hope that this novel approach may lead to greater improvements in vision performance than those provided so far by conventional patching in anisometropic amblyopic children.Trial registrationThis protocol was registered with ClinicalTrials.gov (NCT04819386) on 29 March 2021.
OCT biomarkers related to subthreshold micropulse laser treatment effect in central serous chorioretinopathy
Authors: Zheng Fang , He Jingliang , Su Zhitao , Liu Ye , Xu Yufeng , Liu Lei , Ye Panpan 
Published: June 2022

Abstract
Background
To identify the OCT biomarkers related to the anatomical outcomes in eyes with central serous chorioretinopathy (CSCR) after subthreshold micropulse laser (SML) treatment.

Methods
Patients with CSCR underwent SML were enrolled in this retrospective study. Only patients who underwent enhanced depth imaging optical coherence tomography (EDI-OCT) examination before and after SML were selected. Patients were divided into two groups based on whether subretinal fluid (SRF) absorbed or not after SML. Group 1 was the SRF resolved group, and Group 2 was the SRF non-resolved group. Factors including age and gender, duration of symptoms, CSCR history, the height of SRF at baseline, retinal pigment epithelium (RPE) /inner choroid alterations, as well as subfoveal choroidal thickness (SFCT) of the affected eye and the fellow eye before and after SML were recorded and compared between two groups. Longitudinal change of SFCT of a subgroup of patients were analyzed.

Results
A total of 58 eyes of 58 patients were involved in this study. SRF of 31 eyes got completely absorbed, and SRF of 27 eyes was retained after SML. Logistic regression analysis revealed baseline SFCT of the affected eye (OR = 1.007, 95% CI: 1.001–1.012, P = 0.019) and RPE/inner choroid alterations (OR = 25.229, 95% CI: 2.890–220.281, P = 0.004) were correlated with SML efficacy. Thirty-three eyes of 33 patients were enrolled in the subgroup analysis. A significant difference of SFCT changes between two groups were demonstrated (P = 0.001). The difference of SFCT between baseline and three months after SML was also related to SRF resolution (OR = 0.952, 95% CI: 0.915–0.990, P = 0.014).

Conclusion
Baseline SFCT, change of SFCT at 3-month after treatment, and RPE/inner choroid alterations were the OCT biomarkers related to SRF resolution after SML treatment.
Compound heterozygous variations in IARS1 cause recurrent liver failure and growth retardation in a Chinese patient: a case report
Authors: Zou Ting-Ting , Sun Hua-Qin , Zhu Yu , He Tian-Tian , Ling Wen-Wu , Zhu Hong-Mei , Lin Zi-Yuan , Liu Yan-Yan , Liu Shan-Ling , Wang He , Zhang Xue-Mei 
Published: June 2022

Abstract
Background
Aminoacyl-tRNA synthetases (ARSs) are enzymes responsible for attaching amino acids to tRNA, which enables protein synthesis. Mutations in isoleucyl-tRNA synthetase (IARS1) have recently been reported to be a genetic cause for growth retardation, intellectual disability, muscular hypotonia, and infantile hepatopathy (GRIDHH).

Case presentation
In this study, we reported an additional case of compound heterozygous missense variations c.701 T > C (p.L234P) and c.1555C > T (p.R519C) in IARS1, which were identified using medical exome sequencing; c.701 T > C (p.L234P) was a novel variant, and c.1555C > T (p.R519C) was found in GnomAD. Unlike other reported patients, this individual presented prominently with recurrent liver failure, which led to her death at an early age of 19 months. She also had significant growth retardation, muscular hypotonia, chubby and flabby face, recurrent loose stools, and abnormal brain computed tomography (CT), while zinc deficiency and hearing loss were not present. Studies in zebrafish embryo modeling recapitulated some of the key phenotypic traits in embryo development, neurodevelopment, liver development, and myogenesis, demonstrating that these variations caused a loss of gene function in IARS1.

Conclusions
We have found a novel mutation point c.701 T > C (p.L234P) in IARS1. Compound heterozygous mutations of c.701 T > C (p.L234P) and c.1555C > T (p.R519C) in IARS1 are pathogenic, which can cause GRIDHH in child.