bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accurate prediction of microvascular invasion occurrence and effective prognostic estimation for patients with hepatocellular carcinoma after radical surgical treatment
Authors: Xiong Yuling , Cao Peng , Lei Xiaohua , Tang Weiping , Ding Chengming , Qi Shuo , Chen Guodong 
Published: September 2022

Abstract
Background
Hepatocellular carcinoma (HCC) is the third most common cause of cancer death worldwide, with an overall 5-year survival rate of less than 18%, which may be related to tumor microvascular invasion (MVI). This study aimed to compare the clinical prognosis of HCC patients with or without MVI after radical surgical treatment, and further analyze the preoperative risk factors related to MVI to promote the development of a new treatment strategy for HCC.

Methods
According to the postoperative pathological diagnosis of MVI, 160 study patients undergoing radical hepatectomy were divided into an MVI-negative group (n = 68) and an MVI-positive group (n = 92). The clinical outcomes and prognosis were compared between the two groups, and then the parameters were analyzed by multivariate logistic regression to construct an MVI prediction model. Then, the practicability and validity of the model were evaluated, and the clinical prognosis of different MVI risk groups was subsequently compared.

Result
There were no significant differences between the MVI-negative and MVI-positive groups in clinical baseline, hematological, or imaging data. Additionally, the clinical outcome comparison between the two groups presented no significant differences except for the pathological grading (P = 0.002) and survival and recurrence rates after surgery (P < 0.001). The MVI prediction model, based on preoperative AFP, tumor diameter, and TNM stage, presented superior predictive efficacy (AUC = 0.7997) and good practicability (high H-L goodness of fit, P = 0.231). Compared with the MVI high-risk group, the patients in the MVI low-risk group had a higher survival rate (P = 0.002) and a lower recurrence rate (P = 0.004).

Conclusion
MVI is an independent risk factor for a poor prognosis after radical resection of HCC. The MVI prediction model, consisting of AFP, tumor diameter, and TNM stage, exhibits superior predictive efficacy and strong clinical practicability for MVI prediction and prognostication, which provides a new therapeutic strategy for the standardized treatment of HCC patients.
Metabolic differences in women with premature ovarian insufficiency: a systematic review and meta-analysis
Authors: Cai Wang-Yu , Luo Xi , Wu Wei , Song Jianyuan , Xie Ning-Ning , Duan Cuicui , Wu Xiao-Ke , Xu Jian 
Published: September 2022

AbstractObjectiveThis review aimed to investigate the metabolic profile of women with premature ovarian insufficiency (POI) compared relative to women with normal ovarian functioning.MethodsA systematic search of PubMed, EMBASE, and the Web of Science for observational studies published up until the 6thof July 2021 that compared the metabolic profile of POI women with a healthy control group were assessed. Mean differences (MD) and 95% confidence interval (CI) were pooled using the fixed or random effect models.ResultsA total of 21 studies involving 1573 women with POI and 1762 control women were included. POI patients presented significantly higher waist circumference, total cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides, and fasting glucose. Additionally, POI patients had marginally higher insulin level. However, the differences in systolic, and diastolic blood pressure were non-significant relative to the control group.ConclusionsPOI is associated with alterations in certain metabolic parameters compared to control women. This finding highlights the importance of early screening and the lifelong management of metabolic health for women with POI.
Comparing two advance care planning conversation activities to motivate advance directive completion in underserved communities across the USA: The Project Talk Trial study protocol for a cluster, randomized controlled trial
Authors: Van Scoy Lauren J. , Levi Benjamin H. , Bramble Cindy , Calo William , Chinchilli Vernon M. , Currin Lindsey , Grant Denise , Hollenbeak Christopher , Katsaros Maria , Marlin Sara , Scott Allison M. , Tucci Amy , VanDyke Erika , Wasserman Emily , Witt Pamela , Green Michael J. 
Published: September 2022

Abstract
Background
Advance care planning (ACP) is a process involving conversations between patients, loved ones, and healthcare providers that consider patient preferences for the types of medical therapies received at the end of life. Underserved populations, including Black, Hispanic, rural, and low-income communities are less likely to engage in ACP than other communities, a health inequity that results in lower-quality care and reduced hospice utilization. The purpose of this trial is to compare efficacy of two interventions intended to motivate ACP (particularly advance directive completion) for those living in underserved communities.

Methods
This 3-armed cluster, randomized controlled mixed methods design is being conducted in 75 community venues in underserved communities across the USA. The goal of the trial is to compare the efficacy of two interventions at motivating ACP. Arm 1 uses an end-of-life conversation game (Hello); Arm 2 uses a nationally utilized workshop format for ACP conversations (The Conversation Project); and Arm 3 uses an attention control game (TableTopics). Events are held in partnership with 75 local community-based host organizations and will involve 1500 participants (n=20 per event). The primary outcome is completion of a visually verified advance directive at 6 months post-event. Primary analyses compare efficacy of each intervention to each other and the control arm. Secondary mixed methods outcomes include (a) other ACP behaviors and engagement; (b) communication quality; (c) impact of sociocultural environment on ACP (via qualitative interviews); and (d) implementation and sustainability. Subgroup analyses examine outcomes for Black, Hispanic, and rural groups in particular.

Discussion
This trial will add to the evidence base behind various conversational ACP interventions, examine potential mechanisms of action for such interventions, and provide qualitative data to better understand the sociocultural environment of how community-based ACP interventions are experienced by underserved populations. Results will also provide important data for future researchers to learn whether visual verification of advance directives is necessary or whether reliance on self-reported outcomes is of comparable value. Data from this study will inform ways to effectively motivate underserved communities to participate in advance care planning.

Trial registration
ClinicalTrials.gov NCT04612738. Registered on October 12, 2020. All information from the WHO Trial Registration Data Set can be found within the protocol.
Increasing the effectiveness of psychotherapy in routine care through blended therapy with transdiagnostic online modules (PsyTOM): study protocol for a randomized controlled trial
Authors: Schaeuffele Carmen , Heinrich Manuel , Behr Solveig , Fenski Friederike , Hammelrath Leona , Zagorscak Pavle , Jansen Alessa , Pohl Steffi , Boettcher Johanna , Knaevelsrud Christine 
Published: September 2022

AbstractBackgroundIn blended therapy, face-to-face psychotherapy and Internet-based interventions are combined. Blended therapy may be advantageous for patients and psychotherapists. However, most blended interventions focus on cognitive behavioral therapy or single disorders, making them less suitable for routine care settings.MethodsIn a randomized controlled trial, we will compare blended therapy and face-to-face therapy in routine care. We intend to randomize 1152 patients nested in 231 psychotherapists in a 1:1 ratio. Patients in the blended therapy group will receive access to a therapeuticonlineintervention (TONI). TONI contains 12 transdiagnostic online modules suited for psychodynamic, cognitive behavioral, and systemic therapy. Psychotherapists decide which modules to assign and how to integrate TONI components into the psychotherapeutic process to tailor treatment to their patients’ specific needs. We will assess patients at baseline, 6 weeks, 12 weeks, and 6 months. Patients enrolled early in the trial will also complete assessments at 12 months. The primary outcomes are depression and anxiety at 6-month post-randomization, as measured by PHQ-8 and GAD-7. The secondary outcomes include satisfaction with life, level of functioning, personality traits and functioning, eating pathology, sexual problems, alcohol/drug use, satisfaction with treatment, negative effects, and mental health care utilization. In addition, we will collect several potential moderators and mediators, including therapeutic alliance, agency, and self-efficacy. Psychotherapists will also report on changes in symptom severity and therapeutic alliance. Qualitative interviews with psychotherapists and patients will shed light on the barriers and benefits of the blended intervention. Furthermore, we will assess significant others of enrolled patients in a sub-study.DiscussionThe integration of online modules which use a common therapeutic language and address therapeutic principles shared across therapeutic approaches into regular psychotherapy has the potential to improve the effectiveness of psychotherapy and transfer it into everyday life as well help save therapists’ resources and close treatment gaps. A modular and transdiagnostic setup of the blended intervention also enables psychotherapists to tailor their treatment optimally to the needs of their patients.Trial registrationGerman Clinical Trials Register (DRKS) DRKS00028536. Registered on 07.06.2022.
Sequencing individual genomes with recurrent genomic disorder deletions: an approach to characterize genes for autosomal recessive rare disease traits
Authors: Yuan Bo , Schulze Katharina V. , Assia Batzir Nurit , Sinson Jefferson , Dai Hongzheng , Zhu Wenmiao , Bocanegra Francia , Fong Chin-To , Holder Jimmy , Nguyen Joanne , Schaaf Christian P. , Yang Yaping , Bi Weimin , Eng Christine , Shaw Chad , Lupski James R. , Liu Pengfei 
Published: September 2022

Abstract
Background
In medical genetics, discovery and characterization of disease trait contributory genes and alleles depends on genetic reasoning, study design, and patient ascertainment; we suggest a segmental haploid genetics approach to enhance gene discovery and molecular diagnostics.

Methods
We constructed a genome-wide map for nonallelic homologous recombination (NAHR)-mediated recurrent genomic deletions and used this map to estimate population frequencies of NAHR deletions based on large-scale population cohorts and region-specific studies. We calculated recessive disease carrier burden using high-quality pathogenic or likely pathogenic variants from ClinVar and gnomAD. We developed a NIRD (NAHR deletion Impact to Recessive Disease) score for recessive disorders by quantifying the contribution of NAHR deletion to the overall allele load that enumerated all pairwise combinations of disease-causing alleles; we used a Punnett square approach based on an assumption of random mating. Literature mining was conducted to identify all reported patients with defects in a gene with a high NIRD score; meta-analysis was performed on these patients to estimate the representation of NAHR deletions in recessive traits from contemporary human genomics studies. Retrospective analyses of extant clinical exome sequencing (cES) were performed for novel rare recessive disease trait gene and allele discovery from individuals with NAHR deletions.

Results
We present novel genomic insights regarding the genome-wide impact of NAHR recurrent segmental variants on recessive disease burden; we demonstrate the utility of NAHR recurrent deletions to enhance discovery in the challenging context of autosomal recessive (AR) traits and biallelic variation. Computational results demonstrate new mutations mediated by NAHR, involving recurrent deletions at 30 genomic regions, likely drive recessive disease burden for over 74% of loci within these segmental deletions or at least 2% of loci genome-wide. Meta-analyses on 170 literature-reported patients implicate that NAHR deletions are depleted from the ascertained pool of AR trait alleles. Exome reanalysis of personal genomes from subjects harboring recurrent deletions uncovered new disease-contributing variants in genes including COX10, ERCC6, PRRT2, and OTUD7A.

Conclusions
Our results demonstrate that genomic sequencing of personal genomes with NAHR deletions could dramatically improve allele and gene discovery and enhance clinical molecular diagnosis. Moreover, results suggest NAHR events could potentially enable human haploid genetic screens as an approach to experimental inquiry into disease biology.
Altered methylation pattern in EXOC4 is associated with stroke outcome: an epigenome-wide association study
Authors: Cullell Natalia , Soriano-Tárraga Carolina , Gallego-Fábrega Cristina , Cárcel-Márquez Jara , Muiño Elena , Llucià-Carol Laia , Lledós Miquel , Esteller Manel , de Moura Manuel Castro , Montaner Joan , Rosell Anna , Delgado Pilar , Martí-Fábregas Joan , Krupinski Jerzy , Roquer Jaume , Jiménez-Conde Jordi , Fernández-Cadenas Israel 
Published: September 2022

Abstract
Background and purpose
The neurological course after stroke is highly variable and is determined by demographic, clinical and genetic factors. However, other heritable factors such as epigenetic DNA methylation could play a role in neurological changes after stroke.

Methods
We performed a three-stage epigenome-wide association study to evaluate DNA methylation associated with the difference between the National Institutes of Health Stroke Scale (NIHSS) at baseline and at discharge (ΔNIHSS) in ischaemic stroke patients. DNA methylation data in the Discovery (n = 643) and Replication (n = 62) Cohorts were interrogated with the 450 K and EPIC BeadChip. Nominal CpG sites from the Discovery (p value < 10–06) were also evaluated in a meta-analysis of the Discovery and Replication cohorts, using a random-fixed effect model. Metabolic pathway enrichment was calculated with methylGSA. We integrated the methylation data with 1305 plasma protein expression levels measured by SOMAscan in 46 subjects and measured RNA expression with RT-PCR in a subgroup of 13 subjects. Specific cell-type methylation was assessed using EpiDISH.

Results
The meta-analysis revealed an epigenome-wide significant association in EXOC4 (p value = 8.4 × 10–08) and in MERTK (p value = 1.56 × 10–07). Only the methylation in EXOC4 was also associated in the Discovery and in the Replication Cohorts (p value = 1.14 × 10–06 and p value = 1.3 × 10–02, respectively). EXOC4 methylation negatively correlated with the long-term outcome (coefficient = − 4.91) and showed a tendency towards a decrease in EXOC4 expression (rho = − 0.469, p value = 0.091). Pathway enrichment from the meta-analysis revealed significant associations related to the endocytosis and deubiquitination processes. Seventy-nine plasma proteins were differentially expressed in association with EXOC4 methylation. Pathway analysis of these proteins showed an enrichment in natural killer (NK) cell activation. The cell-type methylation analysis in blood also revealed a differential methylation in NK cells.

Conclusions
DNA methylation of EXOC4 is associated with a worse neurological course after stroke. The results indicate a potential modulation of pathways involving endocytosis and NK cells regulation.
Dramatic impacts on brain pathology, anxiety, and cognitive function in the knock-in APPNL-G-F mouse model of Alzheimer disease following long-term voluntary exercise
Authors: Mehla Jogender , Deibel Scott H. , Karem Hadil , Hossain Shakhawat , Lacoursiere Sean G. , Sutherland Robert J. , Mohajerani Majid H. , McDonald Robert J. 
Published: September 2022

Abstract
Background
An active lifestyle is associated with improved cognitive functions in aged people and may prevent or slow down the progression of various neurodegenerative diseases including Alzheimer’s disease (AD). To investigate these protective effects, male APPNL-G-F mice were exposed to long-term voluntary exercise.

Methods
Three-month-old AD mice were housed in a cage supplemented with a running wheel for 9 months for long-term exercise. At the age of 12 months, behavioral tests were completed for all groups. After completing behavioral testing, their brains were assessed for amyloid pathology, microgliosis, and cholinergic cells.

Results
The results showed that APPNL-G-F mice allowed to voluntarily exercise showed an improvement in cognitive functions. Furthermore, long-term exercise also improved anxiety in APPNL-G-F mice as assessed by measuring thigmotaxis in the Morris water task. We also found reductions in amyloid load and microgliosis, and a preservation of cholinergic cells in the brain of APPNL-G-F mice allowed to exercise in their home cages. These profound reductions in brain pathology associated with AD are likely responsible for the observed improvement of learning and memory functions following extensive and regular exercise.

Conclusion
These findings suggest the potential of physical exercise to mitigate the cognitive deficits in AD.
Immunoglobulin G4-related disease diagnosed by prostate biopsy: a case report
Authors: Aoki Shigeyuki , Morinaga Shingo , Kawai Naoki , Tanaka Haruna , Kanematsu Keiko , Tsuchiya Nanami , Nonomura Sayuri , Ozawa Akiko , Imai Rie , Takahashi Ryoko , Sawada Tomoko , Futamachi Ruriko , Yamada Yoshiaki 
Published: September 2022

Abstract
Background
Immunoglobulin G4-related disease is characterized by swelling of various organs throughout the body and nodules/hypertrophic lesions. However, its cause remains unknown. We report a case of immunoglobulin G4-related disease that was diagnosed based on the histopathological findings of prostate biopsy.

Case presentation
A 72-year-old Japanese man had been treated by a nearby doctor for hypertension, but subsequently developed lower urinary tract symptoms and was prescribed an α1 blocker for 1 year. However, the patient was subsequently referred to our department because his symptoms did not improve. Prostate-specific antigen was 1.258 ng/ml; however, the nodule was palpable in the right lobe on digital rectal examination, and magnetic resonance imaging suggested Prostate Imaging and Reporting and Data System category 3. Therefore, transrectal prostate needle biopsy (12 locations) under ultrasound was performed. Histopathological examination revealed no malignant findings, although infiltration of lymphocytes and plasma cells, and partial fibrosis were observed. No remarkable findings of obstructive phlebitis were observed. Immunoglobulin G4-related disease was suspected, and immunoglobulin and immunoglobulin G4 immunostaining was performed. Immunoglobulin G4 positive plasma cells were observed in a wide range, immunoglobulin G4 positive cells were noted at > 10 per high-power field, and the immunoglobulin G4 positive/immunoglobulin G positive cell ratio was > 40%. Serum immunoglobulin G4 levels were high at 1600 mg/dl. Enhanced abdominal computed tomography findings suggested periaortitis. Additionally, multiple lymphadenopathies were observed around the abdominal aorta. The patient was accordingly diagnosed with immunoglobulin G4-related disease definite, diagnosis group (definite). We proposed steroid treatment for periaortic soft tissue lesions and lower urinary tract symptoms; however, the patient was refused treatment. A computed tomography scan 6 months after diagnosis revealed no changes in the soft tissue lesions around the aorta. Follow-up computed tomography examinations will be performed every 6 months.

Conclusion
If immunoglobulin G4-related disease is suspected and a highly invasive examination is required for histopathological diagnosis, this can be performed by a relatively minimally invasive prostate biopsy for patients with lower urinary tract symptoms. Further evidence is needed to choose an optimal candidate for prostate biopsy for lower urinary tract symptoms patients with suspicion of immunoglobulin G4-related disease. For patients with lower urinary tract symptoms with immunoglobulin G4-related disease or a history, performing a prostate biopsy may avoid unnecessary treatment. However, if steroid therapy is ineffective, surgical treatment should be considered.
PICO entity extraction for preclinical animal literature
Authors: Wang Qianying , Liao Jing , Lapata Mirella , Macleod Malcolm 
Published: September 2022

Abstract
Background
Natural language processing could assist multiple tasks in systematic reviews to reduce workflow, including the extraction of PICO elements such as study populations, interventions, comparators and outcomes. The PICO framework provides a basis for the retrieval and selection for inclusion of evidence relevant to a specific systematic review question, and automatic approaches to PICO extraction have been developed particularly for reviews of clinical trial findings. Considering the difference between preclinical animal studies and clinical trials, developing separate approaches is necessary. Facilitating preclinical systematic reviews will inform the translation from preclinical to clinical research.

Methods
We randomly selected 400 abstracts from the PubMed Central Open Access database which described in vivo animal research and manually annotated these with PICO phrases for Species, Strain, methods of Induction of disease model, Intervention, Comparator and Outcome. We developed a two-stage workflow for preclinical PICO extraction. Firstly we fine-tuned BERT with different pre-trained modules for PICO sentence classification. Then, after removing the text irrelevant to PICO features, we explored LSTM-, CRF- and BERT-based models for PICO entity recognition. We also explored a self-training approach because of the small training corpus.

Results
For PICO sentence classification, BERT models using all pre-trained modules achieved an F1 score of over 80%, and models pre-trained on PubMed abstracts achieved the highest F1 of 85%. For PICO entity recognition, fine-tuning BERT pre-trained on PubMed abstracts achieved an overall F1 of 71% and satisfactory F1 for Species (98%), Strain (70%), Intervention (70%) and Outcome (67%). The score of Induction and Comparator is less satisfactory, but F1 of Comparator can be improved to 50% by applying self-training.

Conclusions
Our study indicates that of the approaches tested, BERT pre-trained on PubMed abstracts is the best for both PICO sentence classification and PICO entity recognition in the preclinical abstracts. Self-training yields better performance for identifying comparators and strains.
Dyspnea after discharge from hospital due to pulmonary vein thrombosis after video-assisted left upper lobectomy: a case report
Authors: Kubo Ruiji , Hoshi Takuo , Shu Akae , Yamasaki Yuichiro 
Published: September 2022

Abstract
Background
Thrombus formation at the pulmonary vein transection site is more common in left upper lobectomy than other lobectomies. We report a case of dyspnea and contrast-enhanced computed tomography (CT) findings of pulmonary vein thrombosis after left upper lobectomy.

Case presentation
A 68-year-old man with left lung cancer underwent video-assisted thoracoscopic left upper lobectomy under general anesthesia with thoracic epidural analgesia. He had no postoperative complications and was discharged home on the 5th day postoperatively. He visited the outpatient clinic at 8 days after surgery because of dyspnea and underwent contrast-enhanced CT, which revealed a thrombus at the resected edge of the left upper pulmonary vein. Anticoagulation therapy was started. Thereafter, the thrombus shrank, and the patient’s dyspnea improved.

Conclusions
Left upper lobe resection is particularly associated with pulmonary venous thrombosis, and dyspnea due to pulmonary venous thrombus may develop late after surgery. Postoperative management methods such as anticoagulation and postoperative pain management should be reexamined.