bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemo-radiotherapy plus durvalumab for loco-regional relapse of resected NSCLC
Authors: Borghetti Paolo , Imbrescia Jessica , Volpi Giulia , Scotti Vieri , Aquilano Michele , Bruni Alessio , Franceschini Davide , Ursino Stefano , Ciammella Patrizia , Piperno Gaia , Taraborrelli Maria , Magrini Stefano Maria 
Published: July 2022

Abstract
Background
tumor recurrence after NSCLC surgical resection is the most common cause of treatment failure that sharply reduces the patient’s life expectancy. The optimal treatment strategy for loco-regional recurrences developing after surgical resection in patients with non–small-cell lung cancer (NSCLC) is not established yet.
This report aims to describe the pattern of relapse, PFS, and OS in patients treated with radio-chemotherapy and durvalumab for loco-regional relapse after surgery.

Methods
We conducted a multicenter, retrospective study including subjects who underwent surgical resection for NSCLC and were treated with Pacific protocol after loco-regional relapse.

Results
Twenty-four patients met the inclusion criteria. At the time of diagnosis mean age was 65 years (range 47–78), the majority being male (58.3%). The 12-month progression-free survival rate was 68.7%, the 18-month progression-free survival rate was 45.8%, and the 24-month progression-free survival rate was 34.3%. There were three deaths: the 12-month survival rate was 91%, and the 18-month survival rate was 82.8%.

Conclusions
In this article, we propose a treatment strategy that might prolong post recurrence survival in patients with good performance status experiencing loco-regional relapse after surgery.
Comparison of MLC positioning deviations using log files and establishment of specific assessment parameters for different accelerators with IMRT and VMAT
Authors: Lin Xiutong , Sun Tao , Liu Xiao , Zhang Guifang , Yin Yong 
Published: July 2022

Abstract
Background and purpose
The study evaluated the differences in leaf positioning deviations by the log files of three advanced accelerators with two delivery techniques, and established specific assessment parameters of leaf positioning deviations for different types of accelerators.

Methods
A total of 420 treatment plans with 5 consecutive treatment log files were collected from the Trilogy, TrueBeam and Halcyon accelerators. Millennium MLC was equipped on the Trilogy and TrueBeam accelerators. A jawless design and dual-layer MLC were adopted on the Halcyon accelerator. 70 IMRT and 70 VMAT plans were selected randomly on each accelerator. The treatment sites of all plans included head and neck, chest, breast, pelvis and other sites. The parsing tasks for 2100 log files were proceeded by SunCheck software from Sun Nuclear Corporation. The maximum leaf root mean square (RMS) errors, 95th percentile errors and percentages of different leaf positioning errors were statistically analyzed. The correlations between these evaluation parameters and accelerator performance parameters (maximum leaf speed, mean leaf speed, gantry and arc angle) were analyzed.

Results
The average maximum leaf RMS errors of the Trilogy in the IMRT and VMAT plans were 0.44 ± 0.09 mm and 0.79 ± 0.07 mm, respectively, which were higher than the TrueBeam's 0.03 ± 0.01 mm, 0.03 ± 0.01 mm and the Halcyon's 0.05 ± 0.01 mm, 0.07 ± 0.01 mm. Similar data results were shown in the 95th percentile error. The maximum leaf RMS errors were strongly correlated with the 95th percentile errors (Pearson index > 0.5). The leaf positioning deviations in VMAT were higher than those in IMRT for all accelerators. In TrueBeam and Halcyon, leaf position errors above 1 mm were not found in IMRT and VMAT plans. The main influencing factor of leaf positioning deviation was the leaf speed, which has no strong correlation with gantry and arc angles.

Conclusions
Compared with the quality assurance guidelines, the MLC positioning deviations tolerances of the three accelerators should be tightened. For both IMRT and VMAT techniques, the 95th percentile error and the maximum RMS error are suggested to be tightened to 1.5 and 1 mm respectively for the Trilogy accelerator. In TrueBeam and Halcyon accelerators, the 95th percentile error and maximum RMS error of 1 and 0.5 mm, respectively, are considered appropriate.
Assessment of dose perturbations for metal stent in photon and proton radiotherapy plans for hepatocellular carcinoma
Authors: Lee Boram , Cho Sungkoo , Park Hee Chul , Kang Sang-Won , Kim Jae-Sung , Chung Jin-Beom 
Published: July 2022

Abstract
Background
The present study aimed to investigate the dosimetric impact of metal stent for photon and proton treatment plans in hepatocellular carcinoma.

Methods
With computed tomography data of a water-equivalent solid phantom, dose perturbation caused by a metal stent included in the photon and proton treatment of hepatocellular carcinoma was evaluated by comparing Eclipse and RayStation treatment planning system (TPS) to a Monte Carlo (MC) based dose calculator. Photon and proton plans were created with anterior–posterior/posterior-anterior (AP/PA) fields using a 6 MV beam and AP/PA fields of a wobbling beam using 150 MeV and a 10 cm ridge filter. The difference in dose distributions and dosimetric parameters were compared depending on the stent's positions (the bile duct (GB) and intestinal tract (GI)) and angles (0°, 45°, and 90°). Additionally, the dose variation in the target volume including the stent was comparatively evaluated through dose volume histogram (DVH) analysis. And the comparison of clinical cases was carried out in the same way.

Results
Percentage differences in the dosimetric parameters calculated by MC ranged from − 7.0 to 3.9% for the photon plan and − 33.7 to 4.3% for the proton plan, depending on the angle at which the GB and GI stents were placed, compared to those without the stent. The maximum difference was observed at the minimum dose (Dmin), which was observed in both photon and proton plans in the GB and GI stents deployed at a 90° incidence angle. The parameter differences were greater in the proton plan than in photon plan. The target volume showed various dose variations depending on positions and angles of stent for both beams. Compared with no-stent, the doses within the target volume containing the GI and GB stents for the photon beam were overestimated in the high-dose area at 0°, nearly equal within 1% at 45°, and underestimated at 90°. These doses to the proton beam were underestimated at all angles, and the amount of underdose to the target volume increased with an increase in the stent angle. However, the difference was significantly greater with the proton plan than the photon plan.

Conclusions
Dose perturbations within the target volume due to the presence of the metal stent were not observed in the TPS calculations for photon and proton beams, but MC was used to confirm that there are dose variations within the target volume. The MC results found that delivery of the treatment beam avoiding the stent was the best method to prevent target volume underdose.
Repair of finger pulp defects using a free second toe pulp flap anastomosed with the palmar vein
Authors: Zhang Xiaoli , Wang Ziyu , Ma Xiaoning , Jin Yanyan , Wang Jingxin , Yu Hang , Li Tong , Xiu Xiaolei 
Published: July 2022

Abstract
Purpose
To evaluate the clinical utility of surgical reconstruction of finger pulp defects using a plantar flap derived from the toes, with vascular anastomosis of the toe-finger artery and the plantar-palmar vein of the finger.

Methods
Between April 2018 and November 2020, 29 patients with finger pulp defects underwent treatment via the transplantation of pulp tissue from the second toe, with the plantar vein of the toe and the palmar vein of the finger being anastomosed during this procedure. In addition, an anastomosis of the toe and finger artery and nerve was conducted, with a flap size of 1.0 cm * 0.8 cm–2.3 cm * 4.0 cm being used for such repair. Donor tissue sites were closed without introducing deformities or other complications.

Results
In all patients in the present study, flap tissues survived and did not exhibit evidence of vascular crisis over a mean 16.8-month follow-up period (range 8–24 months). After successful skin flap grafting, they exhibited good elasticity and a soft texture. At three months post-surgery, some patients reported partial recovery of touch sensation in the transplanted tissue, while pain recovery was evident in some patients at 4–6 months post-surgery. No deformities or other complications were observed at the donor site, and the ability of patients to walk normally was not impaired.

Conclusion
The anastomosis of toe plantar flaps with the palmar vein can facilitate the repair of finger pulp injuries without the need to dissect the dorsal vein of the toe, allowing for the suturing of donor tissue sites without causing any deformities or other complications. This surgical approach can easily be conducted with satisfactory clinical outcomes.
Ozone induces autophagy by activating PPARγ/mTOR in rat chondrocytes treated with IL-1β
Authors: Sun Panpan , Xu Weicheng , Zhao Xu , Zhang Cong , Lin Xiaowen , Gong Moxuan , Fu Zhijian 
Published: July 2022

Abstract
Background
Osteoarthritis (OA) is the main cause of older pain and disability. Intra-articular injections of ozone (O3) commonly have been found to have antioxidative and anti-inflammatory effects to reduce pain and improve function in knee osteoarthritis. It has been reported that reduced autophagy in chondrocytes plays an important role in the development of OA. This study aimed to probe the role of O3 on the autophagy in chondrocytes treated with IL-1β.

Methods
Primary chondrocytes were isolated from Wistar rats cartilage within 3 days. The OA chondrocytes model was induced via treatment with IL-1β for 24 h. Then the cells were treated with O3 and GW9662, the inhibitor of PPARγ. Cell viability was assessed by CCK-8. Further, the cells subjected to Western blot analysis, qRT-PCR and immunofluorescence assay. The numbers of autophagosomes were observed via transmission electron microscopy.

Results
30 μg/ml O3 improved the viability of chondrocytes treated with IL-1β. The decreased level of autophagy proteins and the numbers of autophagosomes improved in IL-1β-treated chondrocytes with O3 via activating PPARγ/mTOR. In addition, the qRT-PCR results showed that O3 decreased the levels of IL-6, TNF-α and MMP-3, MMP-13 in chondrocytes treated with IL-1β.

Conclusions
30 μg/ml O3 improved autophagy via activating PPARγ/mTOR signaling and suppressing inflammation in chondrocytes treated with IL-1β.
In reply to the letter to the editor regarding “Comparison of a twin interlocking derotation and compression screw cephalomedullary nail (InterTAN) with a single screw derotation cephalomedullary nail (proximal femoral nail antirotation): a systematic review and meta-analysis for intertrochanteric fractures”
Authors: Nherera Leo , Trueman Paul , Horner Alan , Watson Tracy , Johnstone Alan J. 
Published: July 2022

Abstract
Background
Intertrochanteric hip fractures are common and devastating injuries, especially for the elderly. Surgical treatment is the optimal strategy for managing intertrochanteric fractures as it allows early rehabilitation and functional recovery. The relative effects of internal fixation strategies for intertrochanteric fracture after operation remain limited to relatively small studies which create uncertainty in attempts to establish evidence-based best practice.

Methods
We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) and observational studies to assess the clinical effectiveness of two commonly used intramedullary devices: a twin-screw integrated cephalomedullary nail (InterTAN) versus a single-screw cephalomedullary nail (proximal femoral nail antirotation) in patients with intertrochanteric fractures. The following outcomes were considered: revisions, implant-related failures, non-unions, pain, Harris hip score and intra-operative outcomes. Odds ratios or mean differences with 95% confidence intervals in brackets are reported.

Results
Six studies met the inclusion criteria: two randomised controlled trials and four observational studies enrolling 970 patients with a mean age of 77 years and 64% of patients being female. There was a statistically significant difference (p value < 0.05) for revisions OR 0.27 (0.13–0.56), implant-related failures OR 0.16 (0.09–0.27) and proportion of patients complaining of pain OR 0.50 (0.34–0.74). There was no difference in non-unions and Harris hip score (p value > 0.05). There was a significant difference in blood loss and fluoroscopy usage in favour of PFNA, while no difference in operating times was observed between the two devices.

Conclusions
Our meta-analysis suggests that a twin-screw integrated cephalomedullary nail (InterTAN) is clinically more effective when compared to a single-screw cephalomedullary nail proximal femoral nail antirotation resulting in fewer complications, fewer revisions and fewer patients complaining of pain. No difference has been established regarding non-unions and Harris hip score. Intra-operative outcomes favour PFNA with less blood loss and fluoroscopy usage. Further studies are warranted to explore the cost-effectiveness of these and other implants in managing patients with intertrochanteric fractures.
Crosstalk of organelles in Parkinson’s disease – MiT family transcription factors as central players in signaling pathways connecting mitochondria and lysosomes
Authors: Lang Martin , Pramstaller Peter P. , Pichler Irene 
Published: July 2022

AbstractLiving organisms constantly need to adapt to their surrounding environment and have evolved sophisticated mechanisms to deal with stress. Mitochondria and lysosomes are central organelles in the response to energy and nutrient availability within a cell and act through interconnected mechanisms. However, when such processes become overwhelmed, it can lead to pathologies. Parkinson’s disease (PD) is a common neurodegenerative disorder (NDD) characterized by proteinaceous intracellular inclusions and progressive loss of dopaminergic neurons, which causes motor and non-motor symptoms. Genetic and environmental factors may contribute to the disease etiology. Mitochondrial dysfunction has long been recognized as a hallmark of PD pathogenesis, and several aspects of mitochondrial biology are impaired in PD patients and models. In addition, defects of the autophagy-lysosomal pathway have extensively been observed in cell and animal models as well as PD patients’ brains, where constitutive autophagy is indispensable for adaptation to stress and energy deficiency. Genetic and molecular studies have shown that the functions of mitochondria and lysosomal compartments are tightly linked and influence each other. Connections between these organelles are constituted among others by mitophagy, organellar dynamics and cellular signaling cascades, such as calcium (Ca2+) and mTOR (mammalian target of rapamycin) signaling and the activation of transcription factors. Members of the Microphthalmia-associated transcription factor family (MiT), including MITF, TFE3 and TFEB, play a central role in regulating cellular homeostasis in response to metabolic pressure and are considered master regulators of lysosomal biogenesis. As such, they are part of the interconnection between mitochondria and lysosome functions and therefore represent attractive targets for therapeutic approaches against NDD, including PD. The activation of MiT transcription factors through genetic and pharmacological approaches have shown encouraging results at ameliorating PD-related phenotypes in in vitro and in vivo models. In this review, we summarize the relationship between mitochondrial and autophagy-lysosomal functions in the context of PD etiology and focus on the role of the MiT pathway and its potential as pharmacological target against PD.
Exploring immunotherapy in colorectal cancer
Authors: Weng Junyong , Li Shanbao , Zhu Zhonglin , Liu Qi , Zhang Ruoxin , Yang Yufei , Li Xinxiang 
Published: July 2022

AbstractChemotherapy combined with or without targeted therapy is the fundamental treatment for metastatic colorectal cancer (mCRC). Due to the adverse effects of chemotherapeutic drugs and the biological characteristics of the tumor cells, it is difficult to make breakthroughs in traditional strategies. The immune checkpoint blockades (ICB) therapy has made significant progress in the treatment of advanced malignant tumors, and patients who benefit from this therapy may obtain a long-lasting response. Unfortunately, immunotherapy is only effective in a limited number of patients with microsatellite instability—high (MSI-H), and segment initial responders can subsequently develop acquired resistance. From September 4, 2014, the first anti-PD-1/PD-L1 drug Pembrolizumab was approved by the FDA for the second-line treatment of advanced malignant melanoma. Subsequently, it was approved for mCRC second-line treatment in 2017. Immunotherapy has rapidly developed in the past 7 years. The in-depth research of the ICB treatment indicated that the mechanism of colorectal cancer immune-resistance has become gradually clear, and new predictive biomarkers are constantly emerging. Clinical trials examining the effect of immune checkpoints are actively carried out, in order to produce long-lasting effects for mCRC patients. This review summarizes the treatment strategies for mCRC patients, discusses the mechanism and application of ICB in mCRC treatment, outlines the potential markers of the ICB efficacy, lists the key results of the clinical trials, and collects the recent basic research results, in order to provide a theoretical basis and practical direction for immunotherapy strategies.
Super-enhancer profiling identifies novel critical and targetable cancer survival gene LYL1 in pediatric acute myeloid leukemia
Authors: Fang Fang , Lu Jun , Sang Xu , Tao Yan-Fang , Wang Jian-Wei , Zhang Zi-Mu , Zhang Yong-Ping , Li Xiao-Lu , Xie Yi , Wu Shui-Yan , Chu Xin-Ran , Li Gen , Wu Di , Chen Yan-Ling , Yu Juan-Juan , Jia Si-qi , Feng Chen-xi , Tian Yuan-Yuan , Li Zhi-Heng , Ling Jing , Hu Shao-Yan , Pan Jian 
Published: July 2022

Abstract
Background
Acute myeloid leukemia (AML) is a myeloid neoplasm makes up 7.6% of hematopoietic malignancies. Super-enhancers (SEs) represent a special group of enhancers, which have been reported in multiple cell types. In this study, we explored super-enhancer profiling through ChIP-Seq analysis of AML samples and AML cell lines, followed by functional analysis.

Methods
ChIP-seq analysis for H3K27ac was performed in 11 AML samples, 7 T-ALL samples, 8 B-ALL samples, and in NB4 cell line. Genes and pathways affected by GNE-987 treatment were identified by gene expression analysis using RNA-seq. One of the genes associated with super-enhancer and affected by GNE-987 treatment was LYL1 basic helix-loop-helix family member (LYL1). shRNA mediated gene interference was used to down-regulate the expression of LYL1 in AML cell lines, and knockdown efficiency was detected by RT-qPCR and western blotting. The effect of knockdown on the growth of AML cell lines was evaluated by CCK-8. Western blotting was used to detect PARP cleavage, and flow cytometry were used to determine the effect of knockdown on apoptosis of AML cells.

Results
We identified a total of 200 genes which were commonly associated with super-enhancers in ≧10 AML samples, and were found enriched in regulation of transcription. Using the BRD4 inhibitor GNE-987, we assessed the dependence of AML cells on transcriptional activation for growth and found GNE-987 treatment predominantly inhibits cell growth in AML cells. Moreover, 20 candidate genes were selected by super-enhancer profile and gene expression profile and among which LYL1 was observed to promote cell growth and survival in human AML cells.

Conclusions
In summary, we identified 200 common super-enhancer-associated genes in AML samples, and a series of those genes are cancer genes. We also found GNE-987 treatment downregulates the expression of super-enhancer-associated genes in AML cells, including the expression of LYL1. Further functional analysis indicated that LYL1 is required for AML cell growth and survival. These findings promote understanding of AML pathophysiology and elucidated an important role of LYL1 in AML progression.
Selective block of sensory neuronal T-type/Cav3.2 activity mitigates neuropathic pain behavior in a rat model of osteoarthritis pain
Authors: Itson-Zoske Brandon , Shin Seung Min , Xu Hao , Qiu Chensheng , Fan Fan , Hogan Quinn H. , Yu Hongwei 
Published: July 2022

AbstractBackgroundPeripheral and central nociceptive sensitization is a critical pathogenetic component in osteoarthritis (OA) chronic pain. T-type calcium channel 3.2 (CaV3.2) regulates neuronal excitability and plays important roles in pain processing. We previously identified that enhanced T-type/CaV3.2 activity in the primary sensory neurons (PSNs) of dorsal root ganglia (DRG) is associated with neuropathic pain behavior in a rat model of monosodium iodoacetate (MIA)-induced knee OA. PSN-specific T-type/CaV3.2 may therefore represent an important mediator in OA painful neuropathy. Here, we test the hypothesis that the T-type/CaV3.2 channels in PSNs can be rationally targeted for pain relief in MIA-OA.MethodsMIA model of knee OA was induced in male and female rats by a single injection of 2 mg MIA into intra-knee articular cavity. Two weeks after induction of knee MIA-OA pain, recombinant adeno-associated viruses (AAV)-encoding potent CaV3.2 inhibitory peptide aptamer 2 (CaV3.2iPA2) that have been characterized in our previous study were delivered into the ipsilateral lumbar 4/5 DRG. Effectiveness of DRG-CaV3.2iPA2 treatment on evoked (mechanical and thermal) and spontaneous (conditioned place preference) pain behavior, as well as weight-bearing asymmetry measured by Incapacitance tester, in the arthritic limbs of MIA rats were evaluated. AAV-mediated transgene expression in DRG was determined by immunohistochemistry.ResultsAAV-mediated expression of CaV3.2iPA2 selective in the DRG-PSNs produced significant and comparable mitigations of evoked and spontaneous pain behavior, as well as normalization of weight-bearing asymmetry in both male and female MIA-OA rats. Analgesia of DRG-AAV-CaV3.2iPA1, another potent CaV3.2 inhibitory peptide, was also observed. Whole-cell current-clamp recordings showed that AAV-mediated CaV3.2iPA2 expression normalized hyperexcitability of the PSNs dissociated from the DRG of MIA animals, suggesting that CaV3.2iPA2 attenuated pain behavior by reversing MIA-induced neuronal hyperexcitability.ConclusionsTogether, our results add therapeutic support that T-type/CaV3.2 in primary sensory pathways contributes to MIA-OA pain pathogenesis and that CaV3.2iPAs are promising analgesic leads that, combined with AAV-targeted delivery in anatomically segmental sensory ganglia, have the potential for further development as a peripheral selective T-type/CaV3.2-targeting strategy in mitigating chronic MIA-OA pain behavior. Validation of the therapeutic potential of this strategy in other OA models may be valuable in future study.