bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automated Hypofractionated IMRT treatment planning for early-stage breast Cancer
Authors: Lin Ting-Chun , Lin Chih-Yuan , Li Kai-Chiun , Ji Jin-Huei , Liang Ji-An , Shiau An-Cheng , Liu Liang-Chih , Wang Ti-Hao 
Published: March 2020

Abstract
Background
Hypofractionated whole-breast irradiation is a standard adjuvant therapy for early-stage breast cancer. This study evaluates the plan quality and efficacy of an in-house-developed automated radiotherapy treatment planning algorithm for hypofractionated whole-breast radiotherapy.

Methods
A cohort of 99 node-negative left-sided breast cancer patients completed hypofractionated whole-breast irradiation with six-field IMRT for 42.56 Gy in 16 daily fractions from year 2016 to 2018 at a tertiary center were re-planned with an in-house-developed algorithm. The automated plan-generating C#-based program is developed in a Varian ESAPI research mode. The dose-volume histogram (DVH) and other dosimetric parameters of the automated and manual plans were directly compared.

Results
The average time for generating an autoplan was 5 to 6 min, while the manual planning time ranged from 1 to 1.5 h. There was only a small difference in both the gantry angles and the collimator angles between the autoplans and the manual plans (ranging from 2.2 to 5.3 degrees). Autoplans and manual plans performed similarly well in hotspot volume and PTV coverage, with the autoplans performing slightly better in the ipsilateral-lung-sparing dose parameters but were inferior in contralateral-breast-sparing. The autoplan dosimetric quality did not vary with different breast sizes, but for manual plans, there was worse ipsilateral-lung-sparing (V4Gy) in larger or medium-sized breasts than in smaller breasts. Autoplans were generally superior than manual plans in CI (1.24 ± 0.06 vs. 1.30 ± 0.09, p < 0.01) and MU (1010 ± 46 vs. 1205 ± 187, p < 0.01).

Conclusions
Our study presents a well-designed standardized fully automated planning algorithm for optimized whole-breast radiotherapy treatment plan generation. A large cohort of 99 patients were re-planned and retrospectively analyzed. The automated plans demonstrated similar or even better dosimetric quality and efficacy in comparison with the manual plans. Our result suggested that the autoplanning algorithm has great clinical applicability potential.
Open necrosectomy in acute pancreatitis–obsolete or still useful?
Authors: Husu Henrik Leonard , Kuronen Jouni Antero , Leppäniemi Ari Kalevi , Mentula Panu Juhani 
Published: March 2020

Abstract
Background
Multiple organ failure and early surgery are associated with high morbimortality after open necrosectomy. Data are mostly derived from historical cohorts with early necrosectomy bereft of step-up treatment algorithm implementation. Thus, mostly circumstantial evidence suggests a better clinical course following mini-invasive surgical and endoscopic necrosectomy. We studied the results of open necrosectomy in a contemporary cohort of patients with complicated pancreatic necrosis treated at a tertiary center.

Methods
A retrospective cohort study from a university teaching hospital. Results of 109 consecutive patients treated with open necrosectomy during a 12-year period are reported.

Results
The overall 90-day mortality rate was 22.9%. The 90-day mortality rate was 10.6% if necrosectomy could be delayed until 4 weeks from symptom onset and the necrosis had become walled off on preoperative imaging. The risk factors for 90-day mortality were age over 60 years (OR 19.4), pre-existing co-morbidities (OR 16.9), necrosectomy within 4 weeks (OR 6.5), multiple organ failure (OR 12.2), white blood cell count over 23 × 109 (OR 21.4), and deterioration or prolonged organ failure as an indication for necrosectomy (OR 10.4). None or one of these risk factors was present in 52 patients (47.7% of all patients), and these patients had no mortality.

Conclusion
Late open necrosectomy for walled-off necrosis has a low mortality risk. Open necrosectomy can be done without mortality in the absence of multiple risk factors for surgery.
Optimization of tenocyte lineage-related factors from tonsil-derived mesenchymal stem cells using response surface methodology
Authors: Kwon Soon-Sun , Kim Hyang , Shin Sang-Jin , Lee Seung Yeol 
Published: March 2020

Abstract
Background
In order to optimize the tenogenic differentiation of mesenchymal stem cells (MSCs), researchers should consider various factors. However, this requires testing numerous experimental settings, which is costly and time-consuming. We aimed to assess the differential effects of transforming growth factor beta-3 (TGF-β3) on the tenogenesis of tonsil-derived MSCs (T-MSCs) and bone marrow-derived MSCs (BM-MSCs) using response surface methodology (RSM).

Methods
Bone marrow and tonsillar tissue were collected from four patients; mononuclear cells were separated and treated with 5 or 10 ng/mL of TGF-β3. A full factorial experimental design with a categorical factor of 0 was employed to study the effect of tension based on T-MSCs. Eighty-four trials were fitted with RSM and then used to obtain mathematical prediction models.

Results
Exposure of T-MSCs and BM-MSCs to TGF-β3 increased the expression of scleraxis (SCX), tenomodulin (TNMD), decorin, collagen I, and tenascin C. Expression of most of these factors reached a maximum after 2–3 days of treatment. The model predicted that the values of the tenocyte lineage-related factors assessed would be significantly increased at 2.5 days of culture with 2.7 ng/mL of TGF-β3 for T-MSCs and at 2.3 days of culture regardless of TGF-β3 concentration for BM-MSCs.

Conclusions
This study demonstrated that the RSM prediction of the culture time necessary for the tenogenic differentiation of T-MSCs and BM-MSCs under TGF-β3 stimulation was similar to the experimentally determined time of peak expression of tenocyte-related mRNAs, suggesting the potential of using the RSM approach for optimization of the culture protocol for tenogenesis of MSCs.
Positive deviance for dual-method promotion among women in Uganda: study protocol for a cluster randomized controlled trial
Authors: Kosugi Hodaka , Shibanuma Akira , Kiriya Junko , Ong Ken Ing Cherng , Mucunguzi Stephen , Muzoora Conrad , Jimba Masamine 
Published: March 2020

Abstract
Background
Dual-method use is known as the most reliable protection against unintended pregnancies and sexually transmitted infections, including HIV. However, it is not commonly used in sub-Sharan Africa, especially among women using highly effective contraceptives. This article describes a protocol to evaluate the effect of an intervention formulated under the positive deviance approach for promoting dual-method use in Uganda.

Methods
A total of 150 women will be interviewed using a structured questionnaire to find those practicing dual-method use. In-depth interviews will then be conducted with all women using the dual method and 10 women using only highly effective contraceptives to identify their unique practice. Then, a cluster randomized controlled trial will be conducted to examine the effect of an intervention formulated under the positive deviance approach on dual-method uptake and adherence. Twenty health facilities will be randomized to an intervention or control arm and 480 women will be enrolled in each group. The participants will be followed up for 8 months.

Discussion
This trial focuses on women who already adapted dual-method use and identifies their unique solutions to promote dual-method use. This trial could tackle barriers for dual-method use, which expert outsiders may fail to recognize, by analyzing and promulgating their unique behaviors. This study could provide evidence that the positive deviance approach can address unintended pregnancies and sexually transmitted infections as well as other health problems which usual approaches have failed to address.

Trial registration
UMIN-CTR Clinical Trial, UMIN000037065. Registered on 14 June 2019.
The antischistosomal potential of GSK-J4, an H3K27 demethylase inhibitor: insights from molecular modeling, transcriptomics and in vitro assays
Authors: Lobo-Silva Jessica , Cabral Fernanda J. , Amaral Murilo S. , Miyasato Patrícia A. , de Freitas Rafaela Paula , Pereira Adriana S. A. , Khouri Mariana I. , Barbosa Mayra M. F. , Ramos Pablo I. P. , Leite Luciana C. C. , Asojo Oluwatoyin A. , Nakano Eliana , Verjovski-Almeida Sergio , Farias Leonardo P. 
Published: March 2020

Abstract
Background
Schistosomiasis chemotherapy is largely based on praziquantel (PZQ). Although PZQ is very safe and tolerable, it does not prevent reinfection and emerging resistance is a primary concern. Recent studies have shown that the targeting of epigenetic machinery in Schistosoma mansoni may result in severe alterations in parasite development, leading to death. This new route for drug discovery in schistosomiasis has focused on classes of histone deacetylases (HDACs) and histone acetyltransferases (HATs) as epigenetic drug targets. Schistosoma histone demethylases also seem to be important in the transition of cercariae into schistosomula, as well as sexual differentiation in adult worms.

Methods
The Target-Pathogen database and molecular docking assays were used to prioritize the druggability of S. mansoni histone demethylases. The transcription profile of Smp_03400 was re-analyzed using available databases. The effect of GSK-J4 inhibitor in schistosomula and adult worms’ motility/viability/oviposition was assessed by in vitro assays. Ultrastructural analysis was performed on adult worms exposed to GSK-J4 by scanning electron microscopy, while internal structures and muscle fiber integrity was investigated by confocal microscopy after Langeronʼs carmine or phalloidin staining.

Results
The present evaluation of the potential druggability of 14 annotated S. mansoni demethylase enzymes identified the S. mansoni ortholog of human KDM6A/UTX (Smp_034000) as the most suitable druggable target. In silico analysis and molecular modeling indicated the potential for cofactor displacement by the chemical probe GSK-J4. Our re-analysis of transcriptomic data revealed that Smp_034000 expression peaks at 24 h in newly transformed schistosomula and 5-week-old adult worms. Moreover, this gene was highly expressed in the testes of mature male worms compared to the rest of the parasite body. In in vitro schistosome cultures, treatment with GSK-J4 produced striking effects on schistosomula mortality and adult worm motility and mortality, as well as egg oviposition, in a dose- and time-dependent manner. Unexpectedly, western blot assays did not demonstrate overall modulation of H3K27me3 levels in response to GSK-J4. Confocal and scanning electron microscopy revealed the loss of original features in muscle fibers and alterations in cell-cell contact following GSK-J4 treatment.

Conclusions
GSK-J4 presents promising potential for antischistosomal control; however, the underlying mechanisms warrant further investigation.
Pralatrexate as a bridge to allogeneic hematopoietic stem cell transplantation in a patient with advanced-stage extranodal nasal-type natural killer/T cell lymphoma refractory to first-line chemotherapy: a case report
Authors: Liu Yao-Chung , Lin Ting-An , Wang Hao-Yuan , Ko Po-Shen , Liu Chia-Jen , Hsiao Liang-Tsai , Chien Sheng-Hsuan , Gau Jyh-Pyng 
Published: March 2020

Abstract
Background
Extranodal natural killer/T cell lymphoma, nasal type, is one of the more common subtypes of mature T cell lymphoma, especially in the Far East Asian population. This aggressive histologic subtype of peripheral T cell lymphomas is frequently susceptible to exposure of Epstein–Barr virus infection. The optimal treatment is not well elucidated. For stage IV disseminated extranodal natural killer/T cell lymphoma, induction chemotherapy with consolidative autologus or allogeneic hematopoietic stem cell transplantation is recommended as the major first-line treatment. However, there is controversy over which type of chemotherapy is most appropriate and effective as a bridge to autologus or allogeneic hematopoietic stem cell transplantation in patients with newly diagnosed disseminated advanced-stage or relapsed extranodal natural killer/T cell lymphoma because of cancer chemoresistance or associated complications. Pralatrexate is the first US Food and Drug Administration-approved novel agent for the treatment of refractory/recurrent peripheral T cell lymphomas. In our case, pralatrexate was used as a successful bridge to allogeneic hematopoietic stem cell transplantation in a patient with advanced-stage disseminated extranodal natural killer/T cell lymphoma refractory to first-line chemotherapy.

Case presentation
We presented a case report of a 29-year-old Asian man diagnosed as having stage IV disseminated extranodal natural killer/T cell lymphoma, nasal type, with skin and bone marrow involvement, whose disease was primary refractory to first-line dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide chemotherapy, but obviously responded to treatment with two cycles of single-agent pralatrexate treatment. Monitoring Epstein–Barr virus viremia revealed dramatic downregulation. In addition to complete remission of the involvement of bone marrow and nasal cavity, skin involvement also obtained partial remission. The extranodal natural killer/T cell lymphoma successfully achieved complete remission after a bridge to allogeneic hematopoietic stem cell transplantation.

Conclusions
This is the first study to present pralatrexate as a successful bridge to allogeneic hematopoietic stem cell transplantation in a 29-year-old Asian male patient with advanced-stage extranodal natural killer/T cell lymphoma refractory to first-line dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide chemotherapy. This case provides a novel treatment opinion for extranodal natural killer/T cell lymphoma, especially for the Far East Asian population.
Accuracy in dosimetry of diagnostic agents: impact of the number of source tissues used in whole organ S value-based calculations
Authors: Josefsson Anders , Siritantikorn Klaikangwol , Ranka Sagar , de Amorim de Carvalho Jose Willegaignon , Buchpiguel Carlos Alberto , Sapienza Marcelo Tatit , Bolch Wesley E. , Sgouros George 
Published: March 2020

Abstract
Background
Dosimetry for diagnostic agents is performed to assess the risk of radiation detriment (e.g., cancer) associated with the imaging agent and the risk is assessed by computing the effective dose coefficient, e. Stylized phantoms created by the MIRD Committee and updated by work performed by Cristy-Eckerman (CE) have been the standard in diagnostic dosimetry. Recently, the ICRP developed voxelized phantoms, which are described in ICRP Publication 110. These voxelized phantoms are more realistic and detailed in describing human anatomy compared with the CE stylized phantoms. Ideally, all tissues should be represented and their pharmacokinetics collected for an as accurate a dosimetric calculation as possible. As the number of source tissues included increases, the calculated e becomes more accurate. There is, however, a trade-off between the number of source tissues considered, and the time and effort required to measure the time-activity curve for each tissue needed for the calculations. In this study, we used a previously published 68Ga-DOTA-TATE data set to examine how the number of source tissues included for both the ICRP voxelized and CE stylized phantoms affected e.

Results
Depending upon the number of source tissues included e varied between 14.0–23.5 μSv/MBq for the ICRP voxelized and 12.4–27.7 μSv/MBq for the CE stylized phantoms. Furthermore, stability in e, defined as a < 10% difference between e obtained using all source tissues compared to one using fewer source tissues, was obtained after including 5 (36%) of the 14 source tissues for the ICRP voxelized, and after including 3 (25%) of the 12 source tissues for the CE stylized phantoms. In addition, a 2-fold increase in e was obtained when all source tissues where included in the calculation compared to when the TIAC distribution was lumped into a single reminder-of-body source term.

Conclusions
This study shows the importance of including the larger tissues like the muscles and remainder-of-body in the dosimetric calculations. The range of e based on the included tissues were less for the ICRP voxelized phantoms using tissue weighting factors from ICRP Publication 103 compared to CE stylized phantoms using tissue weighting factors from ICRP Publication 60.
Mechanism of HMGB1–RAGE in Kawasaki disease with coronary artery injury
Authors: Qian Biying , Huang Hua , Cheng Mingye , Qin Tingting , Chen Tao , Zhao Jianmei 
Published: March 2020

AbstractBackgroundKawasaki disease (KD) is a common, yet unknown etiology disease in Asian countries, which causes acquired heart disease in childhood. It is characterized by an inflammatory acute febrile vasculitis of medium-sized arteries, particularly the coronary arteries. High-mobility group box-1 protein (HMGB1) is a non-histone chromosomal-binding protein present in the nucleus of eukaryotic cells, which contains 215 amino acid residues. Although the cellular signal transduction mechanisms of HMGB1 are currently unclear, the important role of the receptor for advanced glycation end-products (RAGE), the main receptor for HMGB1 has been reported in detail. The purpose of our study was to verify the mechanism and clinical significance of HMGB1-RAGE in coronary artery injury of Kawasaki disease.Methods52 blood samples of patients in KD were collected, and the coronary arteryZscore was calculated according to the echocardiographic results. TheZscore ≥ 2.0 was classified as coronary artery lesions (CAL); otherwise, it was no-coronary artery lesions (NCAL). In addition, the fever group and control group were set. Among them, the fever group were children with fever due to respiratory tract infection at the same time period as KD (heat peak ≥ 38.5 ℃). The normal group were children at a routine physical examination in the outpatient clinic of Nantong University and the physical examination center of the child care insurance, and there were no infectious diseases and heart diseases. The serum levels of HMGB1, RAGE, and NF-κB in each group were detected by ELISA. The animal model of KD was established using the New Zealand young rabbits. We used RT-qPCR/H&E staining/immunohistochemistry/ELISA and western blot to detect the level of HMGB1/RAGE and NF-κB.ResultsIn this study, we found that the HMGB1/RAGE/NF-κB axis was elevated in the serum of children with KD. In addition, an animal model of KD was subsequently prepared to examine the pathological changes of the coronary arteries. We found that the serum levels of HMGB1/RAGE/NF-κB in rabbits with KD were significantly higher than those of the control group. Moreover, the lumen diameter of the coronary artery was slightly enlarged, and the wall of the tube became thinner and deformed. In addition, the HMGB1/RAGE/NF-κB levels in the coronary artery were higher in the rabbits with KD in the acute phase.ConclusionsOn the whole, the findings of this study demonstrate that the expression of HMGB1/RAGE/NF-κB is altered at different stages of KD, suggesting that the HMGB1/RAGE/NF-κB signaling pathway plays an important role in vascular injury in KD. The results of this study may have important implications for the early warning of coronary artery lesions in KD.
Loss of BICD2 in muscle drives motor neuron loss in a developmental form of spinal muscular atrophy
Authors: Rossor Alexander M. , Sleigh James N. , Groves Michael , Muntoni Francesco , Reilly Mary M. , Hoogenraad Casper C. , Schiavo Giampietro 
Published: March 2020

AbstractAutosomal dominant missense mutations in BICD2 cause Spinal Muscular Atrophy Lower Extremity Predominant 2 (SMALED2), a developmental disease of motor neurons. BICD2 is a key component of the cytoplasmic dynein/dynactin motor complex, which in axons drives the microtubule-dependent retrograde transport of intracellular cargo towards the cell soma. Patients with pathological mutations in BICD2 develop malformations of cortical and cerebellar development similar to Bicd2 knockout (−/−) mice. In this study we sought to re-examine the motor neuron phenotype of conditional Bicd2−/− mice. Bicd2−/− mice show a significant reduction in the number of large calibre motor neurons of the L4 ventral root compared to wild type mice. Muscle-specific knockout of Bicd2 results in a similar reduction in L4 ventral axons comparable to global Bicd2−/− mice. Rab6, a small GTPase required for the sorting of exocytic vesicles from the Trans Golgi Network to the plasma membrane is a major binding partner of BICD2. We therefore examined the secretory pathway in SMALED2 patient fibroblasts and demonstrated that BICD2 is required for physiological flow of constitutive secretory cargoes from the Trans Golgi Network to the plasma membrane using a VSV-G reporter assay. Together, these data indicate that BICD2 loss from muscles is a major driver of non-cell autonomous pathology in the motor nervous system, which has important implications for future therapeutic approaches in SMALED2.
Infrared spectra of soil organic matter under a primary vegetation sequence
Authors: Nuzzo A. , Buurman P. , Cozzolino V. , Spaccini R. , Piccolo A. 
Published: March 2020

Abstract
Background
We applied Fourier-Transformed Infrared Spectroscopy (FTIR) techniques in combination with selective humus extractions to investigate in situ the chemical features of organic matter in three soil profiles recently developed from Dutch sand dunes, under well-documented vegetation sequence and containing a relatively simple mineral-organic matter system. Water-soluble and alkaline-soluble extracts were also studied to match the changes of humus in the soil residues.

Results
Diffuse Reflectance Infrared Fourier Transform (DRIFT) and transmission spectra differed in resolution and sensitivity. DRIFT was superior in revealing structural information on the organic matter present in the soil samples whereas transmission spectra showed higher resolution for the bands of inorganic material at lower spectral frequencies. Differences between H and B horizons were due to the amount of hydrophilic organic acids, partly unsaturated, that were extracted by alkali. Extractable carboxylic acids and other hydrophilic compounds such as peptides and carbohydrates were larger in the less developed soils under pine and crowberry than in the more advanced profiles under beech. Humin residues from both H and B horizons retained unextractable aliphatic components and carboxylic groups involved in strong complexes with minerals, thereby confirming other findings that showed the largely aliphatic character of the unextractable humic fraction. Accumulation of poorly-soluble organic materials in these soils occur by protection from biodegradation due both to complexation with soil minerals and to a process by which apolar humic constituents form a separate hydrophobic phase where no biological activity can take place. Transport of poorly soluble compounds from H to B horizons, noticed especially in the more developed profiles, may have occurred through humic aggregates containing hydrophobic phases.

Conclusions
This work shows that the DRIFT technique in combination with soil chemical treatments can be suitably employed to investigate the changes of organic matter in whole soil samples and represents a valid tool to investigate the role of organic matter in soil profile development.