bluuebunny/crossref_metadata_2025 huggingface dataset:
Study protocol of a multicenter phase III randomized controlled trial investigating the efficiency of the combination of neoadjuvant chemotherapy (NAC) and neoadjuvant laparoscopic intraperitoneal hyperthermic chemotherapy (NLHIPEC) followed by R0 gastrectomy with intraoperative HIPEC for advanced gastric cancer (AGC): dragon II trial
Authors: Beeharry Maneesh Kumarsing , Ni Zhen-Tian , Yang Zhong Yin , Zheng Ya Nan , Feng Run Hua , Liu Wen-Tao , Yan Chao , Yao Xue Xin , Li Chen , Yan Min , Zhu Zheng-Gang
Published: March 2020

Background

Even though treatment modalities such as adjuvant systemic radio-chemotherapy and neoadjuvant chemotherapy (NAC) have individually have improved overall survival (OS) and progression-free survival (PFS) rates in advanced Gastric Cancer (AGC), the peritoneum still presides as a common site of treatment failure and disease recurrence. The role of hyperthermic intraperitoneal chemotherapy (HIPEC) has been acknowledged as prophylaxis for peritoneal carcinomatosis (PC) in AGC patients and in this study, we aim at investigating the safety and efficacy of the combination of neoadjuvant laparoscopic HIPEC (NLHIPEC) with NAC in the neoadjuvant phase followed by surgery of curative intent with intraoperative HIPEC followed by adjuvant chemotherapy (AC).

Methods

In this multicenter Phase III randomized controlled trial, 326 patients will be randomly separated into 2 groups into a 1:1 ratio after laparoscopic exploration. The experiment arm will receive the proposed comprehensive Dragon II regimen while the control group will undergo standard R0 D2 followed by 8 cycles of AC with oxaliplatin with S-1 (SOX) regimen. The Dragon II regimen comprises of 1 cycle of NLHIPEC for 60mins at 43 ± 0.5 °C with 80 mg/m2 of Paclitaxel followed by 3 cycles of NAC with SOX regimen and after assessment, standard R0 D2 gastrectomy with intraoperative HIPEC followed by 5 cycles of SOX regimen chemotherapy. The end-points for the study are 5 year PFS, 5 year OS, peritoneal metastasis rate (PMR) and morbidity rate.

Discussion

This study is one of the first to combine NLHIPEC with NAC in the preoperative phase which is speculated to provide local management of occult peritoneal carcinomatosis or peritoneal free cancer cells while NAC will promote tumor downsizing and down-staging. The addition of the intraoperative HIPEC is speculated to manage dissemination due to surgical trauma. Where the roles of intraoperative HIPEC and NAC have individually been investigated, this study provides innovative insight on a more comprehensive approach to management of AGC at high risk of peritoneal recurrence. It is expected that the combination of NLHIPEC with NAC and HIPEC will increase PFS by 15% and decrease PMR after gastrectomy of curative intent.

Trial registration

World Health Organization Clinical Trials - International Registry Platform (WHO-ICTRP) with Registration ID ChiCTR1900024552, Registered Prospectively on the 16th July, 2019.
Investigation of predictability and influence factors of the achieved lenticule thickness in small incision lenticule extraction
Authors: Wu Fang , Yin Houfa , Chen Xinyi , Yang Yabo
Published: March 2020

Background

To evaluate the differences between the predicted and achieved lenticule thickness (ΔLT) after small incision lenticule extraction (SMILE) surgery and investigate relationships between ΔLT and predicted lenticule thickness in SMILE.

Methods

A total of 184 eyes from 184 consecutive patients who underwent SMILE were included in this prospective study. One eye for each patient was randomly selected and included for statistical analysis. To achieve emmetropia, nomogram adds 10% correction of spherical refractive. An ultrasound pachymetry measurement and Scheimpflug camera corneal topography were obtained before and at 3 months after SMILE. The achieved lenticule thickness was calculated by comparing the preoperative examinations with postoperative examinations using ultrasound pachymetry and Pentacam software measurements. The pupil center and corneal vertex were selected as the 2 locations for measurement calculation on Pentacam. Analysis of variance (ANOVA) was performed to compare mean pachymetry values using different instruments. Linear regression analyses were performed between the VisuMax readout lenticule thicknesses and the measured maximum corneal change, between ΔLT and predicted lenticule thickness.

Results

On average, the achieved lenticule thickness measured with ultrasound pachymetry was 13.02 ± 8.87 μm thinner than the predicted lenticule thickness. The proportion of ΔLT in predicted values is 11.9% (ultrasound) and about 15% (Pentacam). Linear regression analysis showed significant relationships between the predicted and each achieved lenticule thickness. Each ΔLT was significantly related to predicted lenticule thickness (ultrasound:R2 = 0.242; pupil center from Pentacam:R2 = 0.230).

Conclusions

An overestimation of achieved lenticule thickness was evident in this study which may exclude eligible SMILE patient. Also, our results showed that 10% increase of spherical refractive correction in the nomogram is appropriate. Furthermore, clinicians should subtract 10% of the predicted lenticule thickness to calculate the residual corneal stroma bed thickness.
Case report of first-episode psychotic symptoms in a patient with early-onset Alzheimer’s disease
Authors: Li Xiao , Xiong Zhenzhen , Liu Yaya , Yuan Yiwen , Deng Junfeng , Xiang Weiyi , Li Zhe
Published: March 2020

Background

Alzheimer’s disease (AD) is a neurodegenerative disorder featuring the behavioral and psychological symptoms of dementia. Patients with early-onset AD that exhibits first as psychotic symptoms usually lack obvious cognitive impairment, so they may be misdiagnosed with late-onset schizophrenia.

Case presentation

We report a patient who had prominent psychotic symptoms at the age of 60 and was initially diagnosed with very-late-onset-schizophrenia-like psychosis. Psychotic symptoms disappeared rapidly after treatment with olanzapine, and the patient later showed extrapyramidal symptoms and decline in cognitive function. Brain magnetic resonance imaging (MRI) showed frontotemporal atrophy, and positron emission tomography (PET) showed extensive areas of hypometabolism in the frontal cortex and head of the caudate nucleus. The patient’s SORL1 gene was found to carry a heterozygrous mutation (c.296A > G). The patient was eventually diagnosed with early-onset AD.

Conclusions

Our case suggests that clinicians should consider the possibility of early-onset AD in middle-aged or elderly patients whose first symptoms are the behavioral and psychological symptoms of dementia. To distinguish early-onset AD from late-onset schizophrenia, clinicians should evaluate cognitive function, perform MRI and PET, and search for SORL1 mutations.
Insight into blood pressure targets for universal coverage of hypertension services in Iran: the 2017 ACC/AHA versus JNC 8 hypertension guidelines
Authors: Mahdavi Mahdi , Parsaeian Mahboubeh , Mohajer Bahram , Modirian Mitra , Ahmadi Naser , Yoosefi Moein , Mehdipour Parinaz , Djalalinia Shirin , Rezaei Nazila , Haghshenas Rosa , Pazhuheian Forough , Madadi Zahra , Sabooni Mahdi , Razi Farideh , Samiee Siamak Mirab , Farzadfar Farshad
Published: March 2020

Background

We compared the prevalence, awareness, treatment, and control of hypertension in Iran based on two hypertension guidelines; the 2017 ACC/AHA –with an aggressive blood pressure target of 130/80 mmHg- and the commonly used JNC8 guideline cut-off of 140/90 mmHg. We shed light on the implications of the 2017 ACC/AHA for population subgroups and high-risk individuals who were eligible for non-pharmacologic and pharmacologic therapies.

Methods

Data was obtained from the Iran national STEPS 2016 study. Participants included 27,738 adults aged ≥25 years as a representative sample of Iranians. Regression models of survey design were used to examine the determinants of prevalence, awareness, treatment, and control of hypertension.

Results

The prevalence of hypertension based on JNC8 was 29.9% (95% CI: 29.2–30.6), which soared to 53.7% (52.9–54.4) based on the 2017 ACC/AHA. The percentage of awareness, treatment, and control were 59.2% (58.0–60.3), 80.2% (78.9–81.4), and 39.1% (37.4–40.7) based on JNC8, which dropped to 37.1% (36.2–38.0), 71.3% (69.9–72.7), and 19.6% (18.3–21.0), respectively, by applying the 2017 ACC/AHA. Based on the new guideline, adults aged 25–34 years had the largest increase in prevalence (from 7.3 to 30.7%). They also had the lowest awareness and treatment rate, contrary to the highest control rate (36.5%) between age groups. Compared with JNC8, based on the 2017 ACC/AHA, 24, 15, 17, and 11% more individuals with dyslipidaemia, high triglycerides, diabetes, and cardiovascular disease events, respectively, fell into the hypertensive category. Yet, based on the 2017 ACC/AHA, 68.2% of individuals falling into the hypertensive category were eligible for receiving pharmacologic therapy (versus 95.7% in JNC8). LDL cholesterol< 130 mg/dL, sufficient physical activity (Metabolic Equivalents≥600/week), and Body Mass Index were found to change blood pressure by − 3.56(− 4.38, − 2.74), − 2.04(− 2.58, − 1.50), and 0.48(0.42, 0.53) mmHg, respectively.

Conclusions

Switching from JNC8 to 2017 ACC/AHA sharply increased the prevalence and drastically decreased the awareness, treatment, and control in Iran. Based on the 2017 ACC/AHA, more young adults and those with chronic comorbidities fell into the hypertensive category; these individuals might benefit from earlier interventions such as lifestyle modifications. The low control rate among individuals receiving treatment warrants a critical review of hypertension services.
Frequency of discussing and documenting advance care planning in primary care: secondary analysis of a multicenter cross-sectional observational study
Authors: Hamano Jun , Oishi Ai , Morita Tatsuya , Kizawa Yoshiyuki
Published: March 2020

Background

To improve the quality of advance care planning (ACP) in primary care, it is important to understand the frequency of and topics involved in the ACP discussion between patients and their family physicians (FPs).

Methods

A secondary analysis of a previous multicenter cross-sectional observational study was performed. The primary outcome of this analysis was the frequency of and topics involved in the ACP discussion between outpatients and FPs. In March 2017, 22 family physicians at 17 clinics scheduled a day to assess outpatients and enrolled patients older than 65 years who were recognized by FPs as having regular visits. We defined three ACP discussion topics: 1) future decline in activities of daily living (ADL), 2) future inability to eat, and 3) surrogate decision makers. FPs assessed whether they had ever discussed any ACP topics with each patient and their family members, and if they had documented the results of these discussions in medical records before patients were enrolled in the present study. We defined patients as being at risk of deteriorating and dying if they had at least 2 positive general indicators or at least 1 positive disease-specific indicator in the Japanese version of the Supportive and Palliative Care Indicators Tool.

Results

In total, 382 patients with a mean age of 77.4 ± 7.9 years were enrolled, and 63.1% were female. Seventy-nine patients (20.7%) had discussed at least one ACP topic with their FPs. However, only 23 patients (6.0%) had discussed an ACP topic with family members and their FPs, with the results being documented in their medical records. The topic of future ADL decline was discussed and documented more often than the other two topics. Patients at risk of deteriorating and dying discussed ACP topics significantly more often than those not at risk of deteriorating and dying (39.4% vs. 16.8%, p < 0.001).

Conclusion

FPs may discuss ACP with some of their patients, but may not often document the results of this discussion in medical records. FPs need to be encouraged to discuss ACP with patients and family members and describe the decisions reached in medical records.
Physical characteristics and antimicrobial properties of Apis mellifera, Frieseomelitta nigra and Melipona favosa bee honeys from apiaries in Trinidad and Tobago
Authors: Brown Elijah , O’Brien Michel , Georges Karla , Suepaul Sharianne
Published: March 2020

Background

Honey is a versatile and complex substance consisting of bioactive chemicals which vary according to many bee and environmental factors. The aim of this study was to assess the physical and antimicrobial properties of five honey samples obtained from three species of bees; two stingless bees, Frieseomelitta nigra and Melipona favosa and one stinging bee, Apis mellifera (fresh and aged honey). Samples were acquired from apiaries across Trinidad and Tobago. An artificial honey, made from sugar, was also used for comparison.

Methods

Physical properties such as appearance, pH, moisture content, sugar content and specific gravity were determined. Antimicrobial activity was assessed utilizing the agar diffusion assay and comparison to a phenol equivalence. The broth microdilution test was performed to determine the minimum inhibitory concentrations (MICs) and the minimum bactericidal concentrations (MBCs) of the five honey samples against four common pathogens, including Staphylococcus aureus, Escherichia coli, Streptococcus pyogenes and Haemophilus influenzae.

Results

All honey samples were acidic, with pH values ranging from 2.88 (M. favosa of Tobago) to 3.91 (fresh A. mellifera). Sugar content ranged from 66.0 to 81.6% with the highest values detected in stinging bee honeys of the A. mellifera (81.6 and 80.5°Bx). Moisture content ranged from 16.9% for aged A. mellifera honey (from Trinidad) to 32.4% for F. nigra honey (from Tobago). The MICs (2 to 16%) and MBCs (2 to 32%) of stingless bee honeys were lower than that of stinging bee and artificial honeys (16 to > 32%). Stingless bee honeys also exhibited a broad spectrum of antimicrobial activity against both Gram-positive and Gram-negative organisms with higher phenol equivalence values (4.5 to 28.6%) than the A. mellifera honeys (0 to 3.4%) against the isolates tested. M. favosa honey of Tobago displayed the greatest antimicrobial activity as indicated by the high phenol equivalence and low MIC and MBC values.

Conclusions

Stingless bee honeys from Tobago showed the greatest antimicrobial activity when compared to the other honeys used in this study. M. favosa honey of Tobago showed the most potential for use as medicinal honey.
GC-MS analysis of Myrtus communis extract and its antibacterial activity against Gram-positive bacteria
Authors: Mir Mushtaq A. , Bashir Nasreena , Alfaify Abdulkhaleg , Oteef Mohammed D. Y.
Published: March 2020

Background

Myrtus communis is a typical plant of Mediterranean area. The different parts of this plant such as berries, branches, and leaves have been used worldwide as a traditional/folk medicine for the treatment of various ailments and diseases.

Methods

Ethanolic leaf extract of the plant was prepared by Soxhlet extraction method. Zone of inhibition, minimum inhibitory concentration and minimal bactericidal concentration were determined by well diffusion method and microplate alamar blue assay. GC-MS analysis was carried out to identify the compounds present in the extract. Microscopy and ImageJ software were used respectively for morphology and cell-length measurements. GraphPad Prism was used for statistical analysis.

Results

The ethanolic extract showed strong inhibitory effect against Gram-positive and acid-fast bacteria with significant inhibition-zone size (9–25 mm), MIC (4.87–78 μg/ml), as well as MBC (0.3–20 mg/ml). However, no effect was observed on the growth of Gram-negative bacteria. The growth inhibition was found to be associated with the damage of cell wall as the extract-treated cells were sensitive to cell wall-targeting antibiotics and displayed the cell wall damage-depicting morphological defects. GC-MS analysis confirmed the presence of novel compounds in addition to the most representative compounds of the essential oils/extracts of M. communis of other country origins.

Conclusion

These results demonstrate that M. communis leaf extract could be the source of compounds to be used for the treatment of Gram-positive bacterial infections. This is the first report, which provides insights into the mechanism of action of the extract in inhibiting the growth of Gram-positive bacteria.
Relationships between academic self-efficacy, learning-related emotions, and metacognitive learning strategies with academic performance in medical students: a structural equation model
Authors: Hayat Ali Asghar , Shateri Karim , Amini Mitra , Shokrpour Nasrin
Published: March 2020

Recognition of the factors affecting the medical students’ academic success is one of the most important challenges and concerns in medical schools. Hence, this study aimed to investigate the mediating effects of metacognitive learning strategies and learning-related emotions in the relationship between academic self-efficacy with academic performance in medical students.

Methods

The present study was carried out on 279 students of medicine studying at Shiraz University of Medical Sciences. The students filled out three questionnaires: academic emotions (AEQ), metacognitive learning strategies, and academic self-efficacy questionnaires. The data were analyzed using SPSS and Smart PLS3.

Results

The results of structural equation modeling revealed that the students’ self-efficacy has an impact on their learning-related emotions and metacognitive learning strategies, and these, in turn, affect the students’ academic performance. Moreover, learning-related emotions influence the metacognitive learning strategies, which in turn mediate the effect of emotions on academic performance.

Discussion

The results of this study revealed that metacognitive strategies and learning-related emotions could play a mediating role in the relationship between students’ self-efficacy and academic performance.
The International Conference on Intelligent Biology and Medicine 2019: computational methods for drug interactions
Authors: Ning Xia , Zhang Chi , Wang Kai , Zhao Zhongming , Mathé Ewy
Published: March 2020

In this editorial, we briefly summarize the International Conference on Intelligent Biology and Medicine 2019 (ICIBM 2019) that was held on June 9–11, 2019 at Columbus, Ohio, USA. Then, we introduce the two research articles included in this supplement issue. These two research articles were selected after careful review of 105 articles that were submitted to the conference, and cover topics on deep learning for drug-target interaction prediction and data mining and visualization of high-order drug-drug interactions.
What matters to me – a web-based preference elicitation tool for clients in long-term care: a user-centred design
Authors: van Leersum Catharina M. , Moser Albine , van Steenkiste Ben , Reinartz Marion , Stoffers Esther , Wolf Judith R. L. M. , van der Weijden Trudy
Published: March 2020

Background

During the process of decision-making for long-term care, clients are often dependent on informal support and available information about quality ratings of care services. However, clients do not take ratings into account when considering preferred care, and need assistance to understand their preferences. A tool to elicit preferences for long-term care could be beneficial. Therefore, the aim of this qualitative descriptive study is to understand the user requirements and develop a web-based preference elicitation tool for clients in need of long-term care.

Methods

We applied a user-centred design in which end-users influence the development of the tool. The included end-users were clients, relatives, and healthcare professionals. Data collection took place between November 2017 and March 2018 by means of meetings with the development team consisting of four users, walkthrough interviews with 21 individual users, video-audio recordings, field notes, and observations during the use of the tool. Data were collected during three phases of iteration: Look and feel, Navigation, and Content. A deductive and inductive content analysis approach was used for data analysis.

Results

The layout was considered accessible and easy during the Look and feel phase, and users asked for neutral images. Users found navigation easy, and expressed the need for concise and shorter text blocks. Users reached consensus about the categories of preferences, wished to adjust the content with propositions about well-being, and discussed linguistic difficulties.

Conclusion

By incorporating the requirements of end-users, the user-centred design proved to be useful in progressing from the prototype to the finalized tool ‘What matters to me’. This tool may assist the elicitation of client’s preferences in their search for long-term care.
Leptospira infection and shedding in dogs in Thailand
Authors: Altheimer Kerstin , Jongwattanapisan Prapaporn , Luengyosluechakul Supol , Pusoonthornthum Rosama , Prapasarakul Nuvee , Kurilung Alongkorn , Broens Els M. , Wagenaar Jaap A. , Goris Marga G. A. , Ahmed Ahmed A. , Pantchev Nikola , Reese Sven , Hartmann Katrin
Published: March 2020

Background

Leptospirosis is a widespread zoonosis and has been recognized as a re-emerging infectious disease in humans and dogs, but prevalence of Leptospira shedding in dogs in Thailand is unknown. The aim of this study was to determine urinary shedding of Leptospira in dogs in Thailand, to evaluate antibody prevalence by microscopic agglutination test (MAT) and enzyme-linked immunosorbent assay (ELISA), and to assess risk factors for Leptospira infection.

In Northern, Northeastern, and Central Thailand, 273 stray (n = 119) or client-owned (n = 154) dogs from rural (n = 139) or urban (n = 134) areas were randomly included. Dogs that had received antibiotics within 4 weeks prior to sampling were excluded. No dog had received vaccination against Leptospira. Urine was evaluated by real-time polymerase chain reaction (PCR) specific for lipL32 gene of pathogenic Leptospira. Additionally, urine was cultured for 6 months in Ellinghausen-McCullough-Johnson-Harris (EMJH) medium. Antibodies were measured by ELISA and MAT against 24 serovars belonging to 15 serogroups and 1 undesignated serogroup. Risk factor analysis was performed with backwards stepwise selection based on Wald.

Results

Twelve of 273 (4.4%; 95% confidence interval (CI): 2.0–6.8%) urine samples were PCR-positive. In 1/273 dogs (0.4%; 95% CI: 0.01–1.1%) Leptospira could be cultured from urine. MAT detected antibodies in 33/273 dogs (12.1%; 95% CI: 8.2–16.0%) against 19 different serovars (Anhoa, Australis, Ballum, Bataviae, Bratislava, Broomi, Canicola, Copenhageni, Coxi, Grippotyphosa, Haemolytica, Icterohaemorrhagiae, Khorat, Paidjan, Patoc, Pyrogenes, Rachmati, Saxkoebing, Sejroe). In 111/252 dogs (44.0%; 95% CI: 37.9–50.2%) immunoglobulin M (IgM) and/or immunoglobulin G (IgG) antibodies were found by ELISA. Female dogs had a significantly higher risk for Leptospira infection (p = 0.023).

Conclusions

Leptospira shedding occurs in randomly sampled dogs in Thailand, with infection rates comparable to those of Europe and the USA. Therefore, the potential zoonotic risk should not be underestimated and use of Leptospira vaccines are recommended.
Correction to: Detecting focal cortical dysplasia lesions from FLAIR-negative images based on cortical thickness
Authors: Feng Cuixia , Zhao Hulin , Tian Maoyu , Lu Miaomiao , Wen Junhai
Published: March 2020

It was highlighted that the original article [1] contained an error in the Quantitative evaluation of Methods. A bracket was misplaced in the formula. This Correction article shows the incorrect and correct formula.
Changing trajectories of serum uric acid and risk of non-alcoholic fatty liver disease: a prospective cohort study
Authors: Ma Zhimin , Xu Chaonan , Kang Xiaoping , Zhang Shan , Li Haibin , Tao Lixin , Zheng Deqiang , Guo Xiuhua , Yang Xinghua
Published: March 2020

Background

It is unclear the role of longitudinal trajectory of serum uric acid (SUA) on the development of non-alcoholic fatty liver disease (NAFLD). We aimed to determine whether longitudinal SUA trajectories are associated with the risk of new-onset NAFLD.

Methods

We explored the relationship between SUA trajectories and NAFLD in a cohort including 3822 participants. Individual’s SUA trajectories from 2012 to 2014 were defined using group-based trajectory modeling analysis in four distinct patterns: trajectory 1 (n = 991, 25.93%), trajectory 2 (n = 1421, 37.18%), trajectory 3 (n = 1156, 30.22%), and trajectory 4 (n = 254, 6.67%). The logistic regression model was used to evaluate the association between SUA changing trajectories and subsequent NAFLD until 2016. Dose–response relationship between SUA changing trajectories and NAFLD risk was evaluated through the testing of trajectory groups as a continuous variable.

Results

The 2-year incidence of NAFLD was 13.27%. Compared with trajectory 1, the adjusted odds risk for NAFLD development was in a dose–response relationship as follows: 1.27 (95% CI 0.91–1.78) for trajectory 2, 1.89 (95% CI 1.29–2.75) for trajectory 3, and 2.34 (95% CI 1.43–3.83) for trajectory 4. And this dose–response relationship was not affected by age, sex, and abdominal obesity.

Conclusions

Higher SUA changing trajectory is a risk factor for NAFLD. This finding highlights the importance of paying attention to SUA changing trajectory on the detection and prevention of NAFLD.
The elevated serum levels of calcineurin and nuclear factor of activated T-cells 1 in children with Kawasaki disease
Authors: Sun Yameng , Liu Jingjing , Geng Zhimin , Tao Yijing , Zheng Fenglei , Wang Ying , Fu Songling , Wang Wei , Xie Chunhong , Zhang Yiying , Gong Fangqi
Published: March 2020

Background

The calcineurin and nuclear factor of activated T-cells (CaN-NFAT) signaling pathway had been found to be associated with Kawasaki disease (KD) susceptibility and coronary artery aneurysm formation as a contributor. To evaluate serum calcineurin (CaN) and nuclear factor of activated T-cells 1(NFAT1) levels in patients with Kawasaki disease (KD).

Methods

Serum levels of CaN and NFAT1 were measured by enzyme-linked immunosorbent assay method in 66 healthy children and 74 KD patients at acute, afebrile and subacute stage.

Results

The serum levels of CaN and NFAT1 increased significantly in the acute stage, and decreased progressively in the afebrile and subacute stage, along with the reduction of C-reactive protein, white blood cells and neutrophil counts. And in the acute stage, the afebrile stage and the subacute stage, the expression of CaN and NFAT1 was upregulated significantly in KD patients compared to that in the healthy control. After the IVIG treatment, the serum levels of CaN and NFAT1 declined significantly in IVIG responders. However, the CaN and NTAT1 levels in the IVIG non-responders declined slowly. And in the afebrile stage, the NFAT1 levels were lower in KD patients with coronary artery lesions (CALs) (268.82 ± 11.96 ng/ml) than those without CALs (285.84 ± 25.13 ng/ml). However, the serum levels of CaN in KD patients with CALs had no significant difference with those in KD patients without CALs.

Conclusions

The specific regulation of CaN and NFAT1 serum levels in the course of KD was suggested that both of them were related in the development of KD.
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

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

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

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

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

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

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

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.
Improvements of operator reverse AM-GM inequality involving positive linear maps
Authors: Karim Shazia , Ali Ilyas , Mushtaq Muhammad
Published: March 2020

In this paper, we shall present some reverse arithmetic-geometric mean operator inequalities for unital positive linear maps. These inequalities improve some corresponding results due to Xue (J. Inequal. Appl. 2017:283, 2017).
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

Background

Kawasaki 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.

Methods

52 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.

Results

In 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.

Conclusions

On 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.