bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep learning-based automatic delineation of the hippocampus by MRI: geometric and dosimetric evaluation
Authors: Pan Kaicheng , Zhao Lei , Gu Song , Tang Yi , Wang Jiahao , Yu Wen , Zhu Lucheng , Feng Qi , Su Ruipeng , Xu Zhiyong , Li Xiadong , Ding Zhongxiang , Fu Xiaolong , Ma Shenglin , Yan Jun , Kang Shigong , Zhou Tao , Xia Bing 
Published: January 2021

Abstract
Background
Whole brain radiotherapy (WBRT) can impair patients’ cognitive function. Hippocampal avoidance during WBRT can potentially prevent this side effect. However, manually delineating the target area is time-consuming and difficult. Here, we proposed a credible approach of automatic hippocampal delineation based on convolutional neural networks.

Methods
Referring to the hippocampus contouring atlas proposed by RTOG 0933, we manually delineated (MD) the hippocampus on the MRI data sets (3-dimensional T1-weighted with slice thickness of 1 mm, n = 175), which were used to construct a three-dimensional convolutional neural network aiming for the hippocampus automatic delineation (AD). The performance of this AD tool was tested on three cohorts: (a) 3D T1 MRI with 1-mm slice thickness (n = 30); (b) non-3D T1-weighted MRI with 3-mm slice thickness (n = 19); (c) non-3D T1-weighted MRI with 1-mm slice thickness (n = 11). All MRIs confirmed with normal hippocampus has not been violated by any disease. Virtual radiation plans were created for AD and MD hippocampi in cohort c to evaluate the clinical feasibility of the artificial intelligence approach. Statistical analyses were performed using SPSS version 23. P < 0.05 was considered significant.

Results
The Dice similarity coefficient (DSC) and Average Hausdorff Distance (AVD) between the AD and MD hippocampi are 0.86 ± 0.028 and 0.18 ± 0.050 cm in cohort a, 0.76 ± 0.035 and 0.31 ± 0.064 cm in cohort b, 0.80 ± 0.015 and 0.24 ± 0.021 cm in cohort c, respectively. The DSC and AVD in cohort a were better than those in cohorts b and c (P < 0.01). There is no significant difference between the radiotherapy plans generated using the AD and MD hippocampi.

Conclusion
The AD of the hippocampus based on a deep learning algorithm showed satisfying results, which could have a positive impact on improving delineation accuracy and reducing work load.
Impact of four-dimensional cone-beam computed tomography on target localization for gastric mucosa-associated lymphoid tissue lymphoma radiotherapy: reducing planning target volume
Authors: Shimohigashi Yoshinobu , Toya Ryo , Saito Tetsuo , Kono Yumiko , Doi Yasuhiro , Fukugawa Yoshiyuki , Watakabe Takahiro , Matsumoto Tadashi , Kai Yudai , Maruyama Masato , Oya Natsuo 
Published: January 2021

Abstract
Background
Radiotherapy of gastric mucosa-associated lymphoid tissue (MALT) lymphoma should be delivered to the entire stomach with planning target volume (PTV) that accounts for variations in stomach volume, respiratory movement, and patient set-up error. In this study, we evaluated whether the use of four-dimensional cone-beam computed tomography (4D-CBCT) reduces the PTV.

Methods
Eight patients underwent radiotherapy with 15 fractions of gastric MALT lymphoma using 4D-CBCT. PTV structures of 5–30 mm margins (5 mm intervals) from the clinical target volume (CTV) delineated based on the 4D-CT images (CTV-4D) were generated. For the target localization, we performed matching based on skin marking (skin matching), bone anatomy (bone matching), and stomach anatomy (4D soft-tissue matching) based on registration between planning CT and 4D-CBCT images from 10 phases. For each patient, we calculated the covering ratio (CR) of the stomach with variable PTV structures, based on the 4D-CBCT images, with a total of 150 phases [CR (%) = (number of covering phases/150 phases) × 100], for three target localization methods. We compared the CR values of the different target localization methods and defined the PTV with an average CR of ≥ 95% for all patients.

Results
The average CR for all patients increased from 17.9 to 100%, 19.6 to 99.8%, and 33.8 to 100%, in the skin, bone, and 4D soft-tissue matchings, respectively, as the PTV structures increased from 5 to 30 mm. The CR obtained by 4D soft-tissue matching was superior to that obtained by skin (P = 0.013) and bone matching (P = 0.008) for a PTV structure of 15 mm margin. The PTV required an additional margin of 20 mm (average CR: 95.2%), 25 mm (average CR: 99.1%), and 15 mm (average CR: 98.0%) to CTV-4D for the skin, bone, and 4D soft-tissue matchings, respectively.

Conclusions
This study demonstrates that the use of 4D-CBCT reduces the PTV when applying 4D soft-tissue matching, compared to skin and bone matchings. Additionally, bone matching does not reduce the PTV as compared with traditional skin matching.
Clinical outcome and pathologic correlation of stereotactic body radiation therapy as a bridge to transplantation for advanced hepatocellular carcinoma: a case series
Authors: Wang Ying-Fu , Dai Yang-Hong , Lin Chun-Shu , Chang Hao-Chih , Shen Po-Chien , Yang Jen-Fu , Hsiang Chih-Weim , Lo Cheng-Hsiang , Huang Wen-Yen 
Published: January 2021

Abstract
Background
Stereotactic body radiotherapy (SBRT) is an emerging modality for hepatocellular carcinoma (HCC). However, there is scant information about its safety and effectiveness in the neoadjuvant setting prior to liver transplantation (LT). We present the clinical outcome and pathologic assessment of SBRT followed by LT for patients with advanced HCC.

Methods
This retrospective study included HCC patients treated with neoadjuvant SBRT prior to LT between 2009 and 2018. Radiographic response and adverse effects, including radiation-induced liver disease (RILD), were evaluated. Pathologic response was assessed by the percentage of tumor necrosis relative to the total tumor volume. Overall survival (OS) and recurrence-free survival (RFS) were calculated using the Kaplan–Meier method.

Results
Fourteen patients underwent SBRT for a total of 25 HCC lesions, followed by LT. The median tumor size was 4.45 cm in diameter, and the median prescribed dose was 45 Gy in 5 fractions. SBRT provided significant AFP reduction, 100% infield control, and a 62.5% response rate. The maximum detected toxicity included grade 3 thrombocytopenia and two grade 3–4 hyperbilirubinemia. One patient developed non-classic RILD. Patients were bridged to LT with a median time of 8.4 months after SBRT, and 23.1% of them achieved a complete pathologic response. The median OS and RFS were 37.8 and 18.3 months from the time of LT, respectively.

Conclusions
SBRT provides favorable tumor control and acceptable adverse effects for patients awaiting LT. Further prospective studies to test SBRT as a bridging therapy for LT are feasible.
Treatment of femoral neck fractures: sliding hip screw or cannulated screws? A meta-analysis
Authors: Xia Yutong , Zhang Wendong , Zhang Zhen , Wang Jingcheng , Yan Lianqi 
Published: January 2021

Abstract
Purpose
Femoral neck fractures are still unsolved problems nowadays; sliding hip screw (SHS) and cannulated compression screw (CCS) are the most commonly used devices. We evaluated the clinical outcomes and complications in the treatment of femoral neck fractures between SHS and CCS in this meta-analysis to find which is better.

Methods
We searched PubMed, Embase, Cochrane library up to 24 August 2020 and retrieved any studies comparing sliding hip screw and cannulated compression screw in treatment of femoral neck fractures; the main outcomes and complications were extracted from the studies which were included.

Results
Nine studies involving 1662 patients (828 patients in the SHS group and 834 patients in the CCS group) were included in this study. SHS had higher rate of avascular necrosis (RR = 1.30, 95% CI 1.08–1.56, p = 0.005), and CCS had higher rate of implant removal (RR = 0.63, 95% CI 0.43–0.93, p = 0.02). No significant statistical difference in non-union, implant failure, infection, replacement, mortality, orthopedic complications, non-orthopedic complications, and total revision between SHS and CCS group.

Conclusion
Both devices have their pros and cons; SHS had a higher rate of avascular necrosis, and CCS had a higher rate of implant removal rate. No significant statistical difference in non-union, implant failure, infection, replacement, mortality, orthopedic complications, non-orthopedic complications, and total revision between SHS and CCS group.
Genipin and insulin combined treatment improves implant osseointegration in type 2 diabetic rats
Authors: Zhang Jiajia , Wang Ya-nan , Jia Tingting , Huang Haiyun , Zhang Dongjiao , Xu Xin 
Published: January 2021

Abstract
Background
Type 2 diabetes mellitus (T2DM) has a harmful effect on the stability and osseointegration of dental implants. T2DM induces mitochondrial damage by inhibiting AMPK signaling, resulting in oxidative stress and poor osteogenesis in the peri-implant bone area. Genipin is a major component of gardenia fruits with strong antioxidant, anti-inflammation, and antidiabetic actions, and it also can activate mitochondrial quality control via the AMPK pathway. The purpose of this study was to investigate the effects of genipin and insulin treatment on implant osseointegration in T2DM rats and explore the underlying mechanisms.

Methods
Streptozotocin-induced diabetic rats received implant surgery in their femurs and were then assigned to five groups that were subjected to different treatments for three months: control group, T2DM group, insulin-treated T2DM group (10 IU/kg), genipin-treated T2DM group (50 mg/kg), and the genipin and insulin combination-treated T2DM group. Then, we regularly assessed the weight and glucose levels of the animals. Rats were euthanized at 3 months after the implantation procedure, and the femora were harvested for microscopic computerized tomography analysis, biomechanical tests, and different histomorphometric assessment.

Results
The results indicated that the highest blood glucose and oxidative stress levels were measured for the T2DM group, resulting in the poorest osseointegration. The combination-treated T2DM group mitigated hyperglycemia and normalized, reactivated AMPK signaling, and alleviated oxidative stress as well as reversed the negative effect of osseointegration. There were beneficial changes observed in the T2DM-genipin and T2DM-insulin groups, but these were less in comparison to the combination treatment group.

Conclusion
Our study suggests that treatment with genipin in combination with insulin could be an effective method for promoting implant osseointegration in T2DM rats, which may be related to AMPK signaling.
Structural alteration of lung parenchyma in patients with NF1: a phenotyping study using multidetector computed tomography (MDCT)
Authors: Avanesov Maxim , Well Lennart , Laqmani Azien , Derlin Thorsten , Riccardi Vincent M. , Adam Gerhard , Mautner Victor-Felix , Salamon Johannes 
Published: January 2021

Abstract
Background
Diffuse interstitial lung disease have been described in Neurofibromatosis type 1 (NF1), but its diversity and prevalence remain unknown. The aim of this study was to assess the prevalence and characteristics of (NF1)-associated lung manifestations in a large single-center study using multidetector computed tomography (MDCT) and to evaluate the smoking history, patients’ age, genetics, and the presence of malignant peripheral nerve sheath tumors (MPNST) as potential influencing factors for lung pathologies.

Methods
In this retrospective study, 71 patients with NF1 were evaluated for the presence of distinctive lung manifestations like reticulations, consolidations, type of emphysema, pulmonary nodules and cysts. All patients underwent F-18-FDG PET/CT scans, which were reviewed by two experienced radiologists in consensus. Patients’ subgroups were formed based on their smoking history (current smokers/previous smokers/never smokers), age (< 12 years, 12–18 years, > 18 years), and presence of MPNST (MPNST/no MPNST). In 57 patients (80%), genetic analysis of sequences coding for the neurofibromin on chromosome 17 was performed, which was correlated with different lung pathologies.

Results
Among all NF1 patients (33 ± 14 years, 56% females), 17 patients (24%) were current smokers and 62 patients (87%) were > 18 years old. Pulmonary cysts, nodules, and paraseptal emphysema were the most common pulmonary findings (35%, 32%, 30%). The presence of pulmonary metastases, MPNST and centrilobular emphysema was associated with smoking. Cysts were observed only in adults, whereas no significant correlation between age and all other pulmonary findings was found (p > 0.05). Presence of MPNST was accompanied by higher rates of intrapulmonary nodules and pulmonary metastasis. Neither the presence nor absence of any of the specific gene mutations was associated with any particular lung pathology (p > 0.05).

Conclusions
All pulmonary findings in NF1 patients occurred independently from specific mutation subtypes, suggesting that many NF1 mutations can cause various pulmonary pathologies. The presence of pulmonary metastases, MPNST and centrilobular emphysema was associated with smoking, indicating the value of smoking secession or the advice not to start smoking in NF1 patients as preventive strategy for clinicians. For screening of pulmonary manifestations in NF1 patients, an MDCT besides medical history and physical examination is mandatory in clinical routine.
Neuroendocrine liver metastasis from the small intestine: Is surgery beneficial for survival?
Authors: Selberherr Andreas , Freermann Simon , Koperek Oskar , Niederle Martin B. , Riss Philipp , Scheuba Christian , Niederle Bruno 
Published: January 2021

Abstract
Background
Neuroendocrine neoplasia of the small intestine (siNEN) are frequently diagnosed with liver metastases. The impact of the presence of liver metastases on overall survival and the necessity of surgery for liver metastasis is discussed controversially. The aim of this study is to evaluate and compare the overall long-term survival of patients with siNENs with and without liver metastasis at initial diagnosis and the possible benefit of surgical treatment as compared to active surveillance of metastases. 123 consecutive patients with siNENs were treated between 1965 and 2016. All clinical and histological records were reevaluated including analysis of the proliferation rates in all specimens. The 1-, 5-, 10- and 20-year overall survival was estimated by Kaplan–Meier analysis for patients with and without liver metastasis and according to the type of treatment (surgical vs. surveillance) of liver metastases if present.

Results
The 1-, 5-, 10- and 20-year overall survival rate was 89.0%, 68.4%, 52.8% and 31.0% in patients without and 89.5%, 69.5%, 33.2% and 3.6% in those with liver metastases. No statistically significant differences were observed comparing the two groups. Within the group of patients with liver metastases, the type of treatment (surgical vs. surveillance) was in favor of patients undergoing surgery. Multivariate analysis showed that the presence of liver metastases upon diagnosis was an individual risk factor associated with worse survival.

Conclusion
The presence of liver metastasis at initial diagnosis does not have a statistically significant influence on survival. Surgery for hepatic metastasis seems to show a benefit for overall survival and may be indicated especially in patients symptomatic due to high tumor burden and serotonin hypersecretion to reduce hormone activity.
Schizophrenia risk ZNF804A interacts with its associated proteins to modulate dendritic morphology and synaptic development
Authors: Dong Fengping , Mao Joseph , Chen Miranda , Yoon Joy , Mao Yingwei 
Published: January 2021

AbstractSchizophrenia (SZ) is a devastating brain disease that affects about 1% of world population. Among the top genetic associations,zinc finger protein 804A(ZNF804A) gene encodes a zinc finger protein, associated with SZ and biolar disorder (BD). Copy number variants (CNVs) ofZNF804Ahave been observed in patients with autism spectrum disorders (ASDs), anxiety disorder, and BD, suggesting thatZNF804Ais a dosage sensitive gene for brain development. However, its molecular functions have not been fully determined. Our previous interactomic study revealed that ZNF804A interacts with multiple proteins to control protein translation and neural development. ZNF804A is localized in the cytoplasm and neurites in the human cortex and is expressed in various types of neurons, including pyramidal, dopaminergic, GABAergic, and Purkinje neurons in mouse brain. To further examine the effect of gene dosage ofZNF804Aon neurite morphology, both knockdown and overexpression ofZNF804Ain primary neuronal cells significantly attenuate dendritic complex and spine formation. To determine the factors mediating these phenotypes, interestingly, three binding proteins of ZNF804A, galectin 1 (LGALS1), fasciculation and elongation protein zeta 1 (FEZ1) and ribosomal protein SA (RPSA), show different effects on reversing the deficits. LGALS1 and FEZ1 stimulate neurite outgrowth at basal level but RPSA shows no effect. Intriguingly, LGALS1 but not FEZ1, reverses the neurite outgrowth deficits induced by ZNF804A knockdown. However, FEZ1 and RPSA but not LGALS1, can ameliorate ZNF804A overexpression-mediated dendritic abnormalities. Thus, our results uncover a critical post-mitotic role of ZNF804A in neurite and synaptic development relevant to neurodevelopmental pathologies.
A receptor-antibody hybrid hampering MET-driven metastatic spread
Authors: Modica Chiara , Basilico Cristina , Chiriaco Cristina , Borrelli Nicla , Comoglio Paolo M. , Vigna Elisa 
Published: January 2021

AbstractBackgroundThe receptor encoded by the MET oncogene and its ligand Hepatocyte Growth Factor (HGF) are at the core of the invasive-metastatic behavior. In a number of instances genetic alterations result in ligand-independent onset of malignancy (METaddiction). More frequently, ligand stimulation of wild-type MET contributes to progression toward metastasis (METexpedience). Thus, while MET inhibitors alone are effective in the first case, combination therapy with ligand inhibitors is required in the second condition.MethodsIn this paper, we generated hybrid molecules gathering HGF and MET inhibitory properties. This has been achieved by ‘head-to-tail’ or ‘tail-to-head’ fusion of a single chain Fab derived from the DN30 MET antibody with a recombinant ‘ad-hoc’ engineered MET extracellular domain (decoyMET), encompassing the HGF binding site but lacking the DN30 epitope.ResultsThe hybrid molecules correctly bind MET and HGF, inhibit HGF-induced MET downstream signaling, and quench HGF-driven biological responses, such as growth, motility and invasion, in cancer cells of different origin. Two metastatic models were generated in mice knocked-in by the human HGF gene: (i) orthotopic transplantation of pancreatic cancer cells; (ii) subcutaneous injection of primary cells derived from a cancer of unknown primary. Treatment with hybrid molecules strongly affects time of onset, number, and size of metastatic lesions.ConclusionThese results provide a strategy to treat metastatic dissemination driven by the HGF/MET axis.
High-resolution analysis of cell-state transitions in yeast suggests widespread transcriptional tuning by alternative starts
Authors: Chia Minghao , Li Cai , Marques Sueli , Pelechano Vicente , Luscombe Nicholas M. , van Werven Folkert J. 
Published: January 2021

Abstract
Background
The start and end sites of messenger RNAs (TSSs and TESs) are highly regulated, often in a cell-type-specific manner. Yet the contribution of transcript diversity in regulating gene expression remains largely elusive. We perform an integrative analysis of multiple highly synchronized cell-fate transitions and quantitative genomic techniques in Saccharomyces cerevisiae to identify regulatory functions associated with transcribing alternative isoforms.

Results
Cell-fate transitions feature widespread elevated expression of alternative TSS and, to a lesser degree, TES usage. These dynamically regulated alternative TSSs are located mostly upstream of canonical TSSs, but also within gene bodies possibly encoding for protein isoforms. Increased upstream alternative TSS usage is linked to various effects on canonical TSS levels, which range from co-activation to repression. We identified two key features linked to these outcomes: an interplay between alternative and canonical promoter strengths, and distance between alternative and canonical TSSs. These two regulatory properties give a plausible explanation of how locally transcribed alternative TSSs control gene transcription. Additionally, we find that specific chromatin modifiers Set2, Set3, and FACT play an important role in mediating gene repression via alternative TSSs, further supporting that the act of upstream transcription drives the local changes in gene transcription.

Conclusions
The integrative analysis of multiple cell-fate transitions suggests the presence of a regulatory control system of alternative TSSs that is important for dynamic tuning of gene expression. Our work provides a framework for understanding how TSS heterogeneity governs eukaryotic gene expression, particularly during cell-fate changes.
SPIN reveals genome-wide landscape of nuclear compartmentalization
Authors: Wang Yuchuan , Zhang Yang , Zhang Ruochi , van Schaik Tom , Zhang Liguo , Sasaki Takayo , Peric-Hupkes Daniel , Chen Yu , Gilbert David M. , van Steensel Bas , Belmont Andrew S. , Ma Jian 
Published: January 2021

AbstractWe report SPIN, an integrative computational method to reveal genome-wide intranuclear chromosome positioning and nuclear compartmentalization relative to multiple nuclear structures, which are pivotal for modulating genome function. As a proof-of-principle, we use SPIN to integrate nuclear compartment mapping (TSA-seq and DamID) and chromatin interaction data (Hi-C) from K562 cells to identify 10 spatial compartmentalization states genome-wide relative to nuclear speckles, lamina, and putative associations with nucleoli. These SPIN states show novel patterns of genome spatial organization and their relation to other 3D genome features and genome function (transcription and replication timing). SPIN provides critical insights into nuclear spatial and functional compartmentalization.