bluuebunny/crossref_metadata_2025 huggingface dataset:
Omega-3 mechanism of action in inflammation and endoplasmic reticulum stress in mononuclear cells from overweight non-alcoholic fatty liver disease participants: study protocol for the “Brazilian Omega Study” (BROS)—a randomized controlled trial
Authors: Batista Ellencristina Silva , da Silva Rios Thaiane , Muñoz Vitor Rosetto , Jesus Joyce Santos , Vasconcelos Marcel Monteiro , da Cunha Diogo Thimóteo , Marques-Rocha Jose Luis , Nakandakari Susana Castelo Branco Ramos , Lara Roberta , da Silva Adelino Sanchez Ramos , Pauli José Rodrigo , Ropelle Eduardo Rochete , Mekary Rania Angelina , de Moura Leandro Pereira , Camargo Enilton Aparecido , Cintra Dennys Esper
Published: December 2021

The low-grade inflammation is pivotal in obesity and its comorbidities; however, the inflammatory proteins are out of target for traditional drug therapy. Omega-3 (ω3) fatty acids can modulate the downstream signaling of Toll-like receptor (TLR) and tumor necrosis factor-α receptor (TNFα) through GPR120, a G-protein-coupled receptor, a mechanism not yet elucidated in humans. This work aims to investigate if the ω3 supplementation, at a feasible level below the previously recommended level in the literature, is enough to disrupt the inflammation and endoplasmic reticulum stress (ER-stress), and also if in acute treatment (3 h) ω3 can activate the GPR120 in peripheral blood mononuclear cells (PBMC) and leukocytes from overweight non-alcoholic fatty liver disease (NAFLD) participants. The R270H variant of the Ffar4 (GPR120 gene) will also be explored about molecular responses and blood lipid profiles. A triple-blind, prospective clinical trial will be conducted in overweight men and women, aged 19–75 years, randomized into placebo or supplemented (2.2 g of ω3 [EPA+DHA]) groups for 28 days. For sample calculation, it was considered the variation of TNFα protein and a 40% dropout rate, obtaining 22 individuals in each group. Volunteers will be recruited among patients with NAFLD diagnosis. Anthropometric parameters, food intake, physical activity, total serum lipids, complete fatty acid blood profile, and glycemia will be evaluated pre- and post-supplementation. In the PBMC and neutrophils, the protein content and gene expression of markers related to inflammation (TNFα, MCP1, IL1β, IL6, IL10, JNK, and TAK1), ER-stress (ATF1, ATF6, IRE1, XBP1, CHOP, eIF2α, eIF4, HSP), and ω3 pathway (GPR120, β-arrestin2, Tab1/2, and TAK1) will be evaluated using Western blot and RT-qPCR. Participants will be genotyped for the R270H (rs116454156) variant using the TaqMan assay. It is hypothesized that attenuation of inflammation and ER-stress signaling pathways in overweight and NAFLD participants will be achieved through ω3 supplementation through binding to the GPR120 receptor.

Trial registration

ClinicalTrials.gov #RBR-7x8tbx. Registered on May 10, 2018, with the Brazilian Registry of Clinical Trials.
Efficacy of Guizhi Fuling Wan for primary dysmenorrhea: protocol for a randomized controlled trial
Authors: Du Yun , Li Yatong , Fu Xianyun , Li Chenjie , Yanan Luo
Published: December 2021

Background

Primary dysmenorrhea (PD) is one of the main gynecological complaints in women of child-bearing age, but limited effective treatments are available. Guizhi Fuling Wan (GFW), one of the most widely known traditional Chinese medicine (TCM) formulations, has been commonly used in clinical practice to treat gynecological disorders in China. In recent years, a growing number of studies have shown that GFW is beneficial for patients with PD. However, the quality of evidence is limited, and there are few studies on specific TCM syndromes of GFW for PD. Therefore, we plan to conduct a randomized controlled trial to explore the efficacy and safety of GFW for PD patients with heat-burning blood-stasis syndrome.

Methods and analysis

The clinical study is a randomized, double-blinded, placebo-controlled trial. Eligible patients will be randomly assigned to the GFW group (treated with GFW) and the control group (treated with a matching placebo) in a 1:1 ratio for three menstrual cycles with a 3-month follow-up. The primary outcome will be the mean change of pain intensity measured by the visual analog scale (VAS). The secondary outcomes will include the Cox Menstrual Symptom Scale (CMSS), the Self-rating Depression Scale (SDS), the Self-rating Anxiety Scale (SAS), and the TCM syndrome scale. Adverse events will also be reported.

Discussion

This randomized trial will be the first rigorous study designed to assess the efficacy and safety of GFW in treating PD with heat-burning blood-stasis syndrome. The finding of this study will provide an objective clinical basis for the use of GFW for PD in the future.

Trial registration

Chinese Clinical Trial Registry ChiCTR2000034118. Registered on 24 June 2020
The influence of a supervised group exercise intervention combined with active lifestyle recommendations on breast cancer survivors’ health, physical functioning, and quality of life indices: study protocol for a randomized and controlled trial
Authors: Riani Costa Luiz Augusto , F. Barreto Raphael , de Leandrini Sarah Milani Moraes , Gurgel Aline Rachel Bezerra , de Sales Gabriel Toledo , Voltarelli Vanessa Azevedo , de Castro Gilberto , Fenton Sally A. M. , Turner James E. , Klausener Christian , Neves Lucas Melo , Ugrinowitsch Carlos , Farah Jose Carlos , Forjaz Cláudia Lúcia de Moraes , Brito Christina May Moran , Brum Patricia Chakur
Published: December 2021

Background

Most cancer patients, under active treatment or not, are sedentary, despite increasing scientific and clinical understanding of the benefits of exercise and physical activity, such as improving quality of life, limiting disease symptoms, decreasing cancer recurrence, and increasing overall survival. Studies have shown that both supervised exercise and unsupervised physical activity programs have low adherence and limited long-term benefits among cancer survivors. Therefore, interventions focused on increasing physical activity levels have clinical and psychological relevance. The present study will examine the feasibility and efficacy of an intervention that combines supervised group exercise with active lifestyle recommendations, analyzing its clinical, psychological, physiological, functional, and immunological effects in breast cancer survivors.

Methods

Women aged 35–75 years who have completed chemotherapy, radiotherapy, and surgery for breast cancer will be recruited from the Cancer Institute of the State of Sao Paulo (ICESP) and take part in a 16-week, parallel-group, randomized, and controlled trial. They will receive a booklet with recommendations for achieving a physically active lifestyle by increasing overall daily movement and undertaking at least 150 min/week of structured exercise. Then, they will be randomized into two groups: the supervised group will take part in two canoeing group exercise sessions every week, and the unsupervised group will increase their overall physical activity level by any means, such as active commuting, daily activities, or home-based exercise. Primary outcome includes aerobic capacity. Secondary outcomes are physical activity, physical functioning, self-reported quality of life, fatigue, presence of lymphedema, body composition, immune function, adherence to physical activity guidelines, and perceptions of self-image.

Discussion

Results should contribute to advance knowledge on the impact of a supervised group exercise intervention to improve aspects related to health, physical functioning, and quality of life in female breast cancer survivors.

Trial registration

Brazilian Registry of Clinical Trials Number: RBR-3fw9xf. Retrospectively Registered on 27 December 2018. Items from the World Health Organization Trial Registration Data Set can be accessed on http://www.ensaiosclinicos.gov.br/rg/RBR-3fw9xf/.
Feasibility and effectiveness of prone position ventilation technique for postoperative acute lung injury in infants with congenital heart disease: study protocol for a prospective randomized study
Authors: Xu Yu-lu , Mi Ya-ping , Zhu Meng-xin , Ren Yue-hong , Gong Wei-juan , Fu Wei-jia , Wang Hui-mei , Ye Lan , Wang Yin , Zhou Xiao-yan , Chen Yan , Chen Yan-yan , Gu Li-qiong , Gu Ying , Jia Bing , Hu Jing , Hu Xiao-jing
Published: December 2021

Background

Prone position ventilation is a widely used lung protection ventilation strategy. The strategy is more convenient to implement in children compared to adults. Due to the precise mechanism of improving oxygenation function, development of pediatric prone ventilation technology has been largely focused on children with acute respiratory distress syndrome. There is a paucity of high-quality studies investigating the effects of prone position ventilation after pediatric cardiac surgery. The purpose of this study is to evaluate the feasibility and effectiveness of prone position ventilation in infants who develop postoperative acute lung injury after surgery for congenital heart disease.

Methods

A single-center, randomized controlled trial of pediatric patients with acute lung injury after surgery for congenital heart disease who will receive prone position ventilation or usual care (control group). A total of 68 children will be enrolled according to the inclusion criteria. The main outcome measures will be lung compliance and oxygenation index. The secondary outcomes will be duration of mechanical ventilation, length of stay in cardiac intensive care unit, reintubation rate, and complication rate.

Discussion

This study will investigate the feasibility and effectiveness of prone position ventilation techniques in children who develop postoperative acute lung injury after surgery for congenital heart disease. The results may help inform strategies to improve airway management after surgery for congenital heart disease.

Trial registration

ClinicalTrials.gov NCT04607993. Initially registered on 29 October 2020.
Solvothermal synthesis of pure and Sn-doped Bi2S3 and the evaluation of their photocatalytic activity on the degradation of methylene blue
Authors: Nkwe Violet M. , Onwudiwe Damian C. , Azeez Mayowa A.
Published: December 2021

Background

A large volume of dye molecules finds its way into the environment, accumulates in water bodies, and makes the aquatic system unsafe to human health. Due to the complex nature of these dye materials, most of the conventional techniques are not effective for their removal. Semiconductor photocatalysis has emerged as a promising technique for  the destruction of organic pollutants under UV or visible light irradiation. Among the semiconductors, Bi2S3 is widely employed in photocatalysis due to its non-toxicity and chemical stability. However, one of its problems is the high recombination rate of the charge, and various methods have been employed to enhance the photo-reactivity. One of  these methods is the incorporation of transition elements.

Results

Herein, a facile solvothermal method was used to prepare Bi2S3 nanorods and needle- shaped Sn doped Bi2S3, using bismuth(III) tris(N-phenyldithiocarbamate) as a single-source precursor. The prepared nanomaterials were characterized, and used as efficient photocatalyst for the photo enhanced degradation of methylene blue (MB) dye under visible light irradiation. The nanomaterials exhibited very good photocatalytic activity towards the photo degradation of MB, showing a degradation rate of up to 83% and 94% within 150 min for the pristine and Sn doped Bi2S3,  respectively.

Conclusion

The enhancement in the photocatalytic activity of the Sn doped Bi2S3 was attributed to the suppression in the recombination rate of the electron‐hole pairs, due to the formation of new energy level below the CB, that was capable of altering the equilibrium concentration of the carrier. This confirmed that Sn doped Bi2S3 could be utilized as valuable cost-efficient catalysts for eliminating methyl blue from aqueous solutions and also possible candidates in environmental pollution treatment.
Morphological and molecular differentiation between Culicoides oxystoma and Culicoides kingi (Diptera: Ceratopogonidae) in Tunisia
Authors: Slama Darine , Baraket Rihab , Remadi Latifa , Chaker Emna , Babba Hamouda
Published: December 2021

Background

Culicoides kingi and Culicoides oxystoma belong to the Schultzei group of biting midges. These two species are vectors of disease in livestock of economic importance. As described in the literature, morphological identification for discrimination between them is still unclear. However, species-specific identification is necessary to solve taxonomic challenges between species and to understand their roles in disease transmission and epidemiology. This study aims to develop accurate tools to discriminate C. oxystoma from C. kingi using traditional morphometry and polymerase chain reaction-restriction fragment length polymorphism (PCR RFLP) assays for use in developing countries.

Methods

Specimens were collected from the region of Kairouan in central Tunisia. A total of 446 C. oxystoma/C. kingi individuals were identified using traditional morphometric analyses combined with PCR–RFLP of the cytochrome c oxidase subunit I gene. Thirteen morphometric measurements were performed from the head, wings, and abdomen of slide-mounted specimens, and six ratios were calculated between these measurements. Multivariate analyses of the morphometric measurements were explored to identify which variables could lead to accurate species identification.

Results

Four variables, namely antennae, wings, spermathecae, and palpus length, were suitable morphometric characteristics to differentiate between the species. Digestion with the SspI restriction enzyme of the PCR product led to good discriminative ability. Molecular procedures and phylogenetic analysis confirmed the efficiency of this simple and rapid PCR–RFLP method.

Conclusions

This study highlights for the first time in Tunisia the presence of C. oxystoma and its discrimination from C. kingi using abdominal measurements and the PCR–RFLP method. This approach could be applied in future epidemiological studies at the national and international levels.

Graphical Abstract
Insecticide susceptibility status and knockdown resistance (kdr) mutation in Aedes albopictus in China
Authors: Wei Yong , Zheng Xueli , He Song , Xin Xuli , Zhang Jiachun , Hu Ke , Zhou Guofa , Zhong Daibin
Published: December 2021

Background

Aedes (Stegomyia) albopictus (Skuse, 1894) is the main vector of dengue virus in China. The resistance to insecticides is a huge obstacle for the control of this species, and determining its resistance status and mechanisms in China is essential for the implementation of vector management strategies.

Methods

We have investigated the larval and adult resistance status of Ae. albopictus to deltamethrin in eight field populations in China. Mutations at the voltage-gated sodium channel gene, related to the knockdown resistance (kdr) effect, were detected by sequencing of PCR products. The eight field populations were examined for pyrethroid resistance using the World Health Organization standard bioassays, and the association between the mutations and phenotypic resistance was tested.

Results

The eight field populations of larvae of Ae. albopictus in China exhibited high resistance to deltamethrin; the RR50 values ranged from 12 (ZJ) to 44 (GZ). Adult bioassay revealed that Ae. albopictus populations were resistant to deltamethrin (mortality rate < 90%), except ZJ population (probably resistant, mortality rate = 93.5%). Long knockdown time in the field populations was consistent with low mortality rates in adult bioassay. F1534S mutation showed increased protection against deltamethrin in all populations except BJ and SJZ populations, whereas I1532T mutation showed increased protection against deltamethrin in only BJ population.

Conclusion

There were different degrees of resistance to deltamethrin in field Ae. albopictus populations in China. The longest knockdown time and lowest mortality rate observed in Ae. albopictus population in Guangzhou indicate the severity of high resistance to deltamethrin. The patchy distribution of deltamethrin resistance and kdr mutations in Ae. albopictus mosquitoes suggests the necessity for resistance management and developing counter measures to mitigate the spread of resistance.

Graphical Abstract
Tandem mass tag (TMT)-based proteomic analysis of Cryptosporidium andersoni oocysts before and after excystation
Authors: Li Dong-Fang , Cui Zhao-Hui , Wang Lu-Yang , Zhang Kai-Hui , Cao Le-Tian , Zheng Shuang-Jian , Zhang Long-Xian
Published: December 2021

Background

Cryptosporidium andersoni initiates infection by releasing sporozoites from oocysts through excystation. However, the proteins involved in excystation are unknown. Determining the proteins that participate in the excystation of C. andersoni oocysts will increase our understanding of the excystation process.

Methods

Cryptosporidium andersoni oocysts were collected and purified from the feces of naturally infected adult cows. Tandem mass tags (TMT), coupled with liquid chromatography–tandem mass spectrometry (LC–MS/MS) proteomic analysis, were used to investigate the proteomic expression profiles of C. andersoni oocysts before and after excystation.

Results

Proteomic analysis identified a total of 1586 proteins, of which 17 were differentially expressed proteins (DEPs) upon excystation. These included 10 upregulated and seven downregulated proteins. The 17 proteins had multiple biological functions associated with control of gene expression at the level of transcription and biosynthetic and metabolic processes. Quantitative real-time RT-PCR of eight selected genes validated the proteomic data.

Conclusions

This study provides information on the protein composition of C. andersoni oocysts as well as possible excystation factors. The data may be useful in identifying genes for diagnosis, vaccine development, and immunotherapy for Cryptosporidium.

Graphical Abstract
Sustained acoustic medicine for the treatment of musculoskeletal injuries: a systematic review and meta-analysis
Authors: Winkler Sandra L. , Urbisci Anthony E. , Best Thomas M.
Published: December 2021

Background

Musculoskeletal injuries account for 10 million work-limited days per year and often lead to both acute and/or chronic pain, and increased chances of re-injury or permanent disability. Conservative treatment options include various modalities, nonsteroidal anti-inflammatory drugs, and physical rehabilitation programs. Sustained Acoustic Medicine is an emerging prescription home-use mechanotransductive device to stimulate cellular proliferation, increase microstreaming and cavitation in situ, and to increase tissue profusion and permeability. This research aims to summarize the clinical evidence on Sustained Acoustic Medicine and measurable outcomes in the literature.

Methods

A systematic literature review was conducted using PubMed, EBSCOhost, Academic Search Complete, Google Scholar and ClinicalTrials.gov to identify studies evaluating the effects of Sustained Acoustic Medicine on the musculoskeletal system of humans. Articles identified were selected based on inclusion criteria and scored on the Downs and Black checklist. Study design, clinical outcomes and primary findings were extracted from included studies for synthesis and meta-analysis statistics.

Results

A total of three hundred and seventy-two participants (372) were included in the thirteen clinical research studies reviewed including five (5) level I, four (4) level II and four (4) level IV studies. Sixty-seven (67) participants with neck and back myofascial pain and injury, one hundred and fifty-six (156) participants with moderate to severe knee pain and radiographically confirmed knee osteoarthritis (Kellgren–Lawrence grade II/III), and one hundred forty-nine (149) participants with generalized soft-tissue injury of the elbow, shoulder, back and ankle with limited function. Primary outcomes included daily change in pain intensity, change in Western Ontario McMaster Osteoarthritis Questionnaire, change in Global Rate of Change, and functional outcome measures including dynamometry, grip strength, range-of-motion, and diathermic heating (temperature measurement).

Conclusion

Sustained Acoustic Medicine treatment provides tissue heating and tissue recovery, improved patient function and reduction of pain. When patients failed to respond to physical therapy, Sustained Acoustic Medicine proved to be a useful adjunct to facilitate healing and return to work. As a non-invasive and non-narcotic treatment option with an excellent safety profile, Sustained Acoustic Medicine may be considered a good therapeutic option for practitioners.
Association between induction of the self-management system for preventing readmission and disease severity and length of readmission in patients with heart failure
Authors: Nakane Eisaku , Kato Takao , Tanaka Nozomi , Kuriyama Tomoari , Kimura Koki , Nishiwaki Shushi , Hamaguchi Toka , Morita Yusuke , Yamaji Yuhei , Haruna Yoshisumi , Haruna Tetsuya , Inoko Moriaki
Published: December 2021

Objective

We recently developed the self-management system using the HF points and instructions to visit hospitals or clinics when the points exceed the pre-specified levels. We found that the self-management system decreased the hospitalization for HF with an increase in unplanned visits and early intervention in the outpatient department. However, it is unclear whether we managed severe HF outpatients who should have been hospitalized. In this study, we aimed to compare HF severity in rehospitalized patients with regard to self-management system use.

Results

We retrospectively enrolled 306 patients (153 patients each in the system user and non-user groups) using propensity scores (PS). We compared HF severity and length of readmission in rehospitalized patients in both groups. During the 1-year follow-up period, 24 system users and 43 non-system users in the PS-matched cohort were hospitalized. There were no significant differences between the groups in terms of brain natriuretic peptide levels at readmission, maximum daily intravenous furosemide dose, percentage of patients requiring intravenous inotropes, duration of hospital stay and in-hospital mortality. These results suggest that the HF severity in rehospitalized patients was not different between the two groups.
Predicting the success of induction of labour using cervical volume
Authors: Patabendige Malitha , Athulathmudali Sanka Rajesh
Published: December 2021

Objectives

Assessing the likelihood of success of induction of labour using cervical volume is an important research question.

Data description

We provide data generated in a prospective observational study which was carried out at North Colombo Teaching Hospital, Ragama, Sri Lanka. Study conducted to compare pre-induction digital cervical assessment, sonographic cervical length, and sonographic cervical volume with vaginal delivery rate within 24 h. Inductions with 100 singleton pregnancies at term were included.
Identification of DNA methylation biomarkers with potential to predict response to neoadjuvant chemotherapy in triple-negative breast cancer
Authors: Meyer Braydon , Clifton Samuel , Locke Warwick , Luu Phuc-Loi , Du Qian , Lam Dilys , Armstrong Nicola J. , Kumar Beena , Deng Niantao , Harvey Kate , Swarbrick Alex , Ganju Vinod , Clark Susan J. , Pidsley Ruth , Stirzaker Clare
Published: December 2021

Neoadjuvant chemotherapy (NAC) is used to treat triple-negative breast cancer (TNBC) prior to resection. Biomarkers that accurately predict a patient’s response to NAC are needed to individualise therapy and avoid chemotoxicity from unnecessary chemotherapy. We performed whole-genome DNA methylation profiling on diagnostic TNBC biopsy samples from the Sequential Evaluation of Tumours Undergoing Preoperative (SETUP) NAC study. We found 9 significantly differentially methylated regions (DMRs) at diagnosis which were associated with response to NAC. We show that 4 of these DMRs are associated with TNBC overall survival (P < 0.05). Our results highlight the potential of DNA methylation biomarkers for predicting NAC response in TNBC.
Imaging features of primary sites and metastatic patterns of angiosarcoma
Authors: Bhaludin Basrull N. , Thway Khin , Adejolu Margaret , Renn Alexandra , Kelly-Morland Christian , Fisher Cyril , Jones Robin L. , Messiou Christina , Moskovic Eleanor
Published: December 2021

Angiosarcomas are rare, aggressive soft tissue sarcomas originating from endothelial cells of lymphatic or vascular origin and associated with a poor prognosis. The clinical and imaging features of angiosarcomas are heterogeneous with a wide spectrum of findings involving any site of the body, but these most commonly present as cutaneous disease in the head and neck of elderly men. MRI and CT are complementary imaging techniques in assessing the extent of disease, focality and involvement of adjacent anatomical structures at the primary site of disease. CT plays an important role in the evaluation of metastatic disease. Given the wide range of imaging findings, correlation with clinical findings, specific risk factors and patterns of metastatic disease can help narrow the differential diagnosis. The final diagnosis should be confirmed with histopathology and immunohistochemistry in combination with clinical and imaging findings in a multidisciplinary setting with specialist sarcoma expertise. The purpose of this review is to describe the clinical and imaging features of primary sites and metastatic patterns of angiosarcomas utilising CT and MRI.
Spontaneous rupture of the ovarian vein in association with nutcracker syndrome: a case report
Authors: Yamamoto Akihito , Kamoi Seiryu , Suzuki Shunji
Published: December 2021

Background

Nutcracker syndrome is a condition in which the left renal vein is pinched between the abdominal aorta and the superior mesenteric artery, resulting in an increase in renal vein pressure and certain symptoms. We report a very rare case of retroperitoneal hematoma caused by the rupture of varicose veins of the left ovary.

Case presentation

A 77-year-old Japanese woman, para 7, experienced sudden left lower abdominal pain. She had no history of trauma or treatment complications. Computed tomography revealed a left retroperitoneal hematoma, but her abdominal pain subsided quickly; thus, urgent treatment was not required. We then scheduled her for an assessment regarding the cause of her bleeding. However, 6 days after the pain onset, abdominal pain symptoms recurred, confirming hematoma regrowth. Magnetic resonance imaging and three-dimensional computed tomography revealed an abnormal vascular network from the left side of the uterus to the left adnexa. Subsequent angiography revealed that the retroperitoneal bleeding originated from rupture of the distended left ovarian vein, which caused blood reflux from the left renal vein to the left ovarian vein. Although angiography confirmed a passage between the left renal vein and inferior vena cava, computed tomography showed obvious stenosis in the left renal vein. In accordance with these findings, we diagnosed the cause of the distention and rupture of the left ovarian vein as nutcracker syndrome. She underwent embolization of the left ovarian vein as hemostasis treatment, and had a good course thereafter.

Conclusions

This is the first report of a spontaneous rupture of the left ovarian vein caused by nutcracker syndrome. Nutcracker syndrome is not yet well known to clinicians and should be considered as part of the differential diagnosis when an abnormal vascular network in the pelvis is found.
Chronic myeloid leukemia stem cells: targeting therapeutic implications
Authors: Mojtahedi Hanieh , Yazdanpanah Niloufar , Rezaei Nima
Published: December 2021

Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm driven by BCR-ABL1 oncoprotein, which plays a pivotal role in CML pathology, diagnosis, and treatment as confirmed by the success of tyrosine kinase inhibitor (TKI) therapy. Despite advances in the development of more potent tyrosine kinase inhibitors, some mechanisms particularly in terms of CML leukemic stem cell (CML LSC) lead to intrinsic or acquired therapy resistance, relapse, and disease progression. In fact, the maintenance CML LSCs in patients who are resistance to TKI therapy indicates the role of CML LSCs in resistance to therapy through survival mechanisms that are not completely dependent on BCR-ABL activity. Targeting therapeutic approaches aim to eradicate CML LSCs through characterization and targeting genetic alteration and molecular pathways involving in CML LSC survival in a favorable leukemic microenvironment and resistance to apoptosis, with the hope of providing a functional cure. In other words, it is possible to develop the combination therapy of TKs with drugs targeting genes or molecules more specifically, which is required for survival mechanisms of CML LSCs, while sparing normal HSCs for clinical benefits along with TKIs.
Residual refinement for interactive skin lesion segmentation
Authors: Jiang Dalei , Wang Yin , Zhou Feng , Ma Hongtao , Zhang Wenting , Fang Weijia , Zhao Peng , Tong Zhou
Published: December 2021

Background

Image segmentation is a difficult and classic problem. It has a wide range of applications, one of which is skin lesion segmentation. Numerous researchers have made great efforts to tackle the problem, yet there is still no universal method in various application domains.

Results

We propose a novel approach that combines a deep convolutional neural network with a grabcut-like user interaction to tackle the interactive skin lesion segmentation problem. Slightly deviating from grabcut user interaction, our method uses boxes and clicks. In addition, contrary to existing interactive segmentation algorithms that combine the initial segmentation task with the following refinement task, we explicitly separate these tasks by designing individual sub-networks. One network is SBox-Net, and the other is Click-Net. SBox-Net is a full-fledged segmentation network that is built upon a pre-trained, state-of-the-art segmentation model, while Click-Net is a simple yet powerful network that combines feature maps extracted from SBox-Net and user clicks to residually refine the mistakes made by SBox-Net. Extensive experiments on two public datasets, PH2 and ISIC, confirm the effectiveness of our approach.

Conclusions

We present an interactive two-stage pipeline method for skin lesion segmentation, which was demonstrated to be effective in comprehensive experiments.
Generation of macrophage containing alveolar organoids derived from human pluripotent stem cells for pulmonary fibrosis modeling and drug efficacy testing
Authors: Heo Hye-Ryeon , Hong Seok-Ho
Published: December 2021

Macrophages are a central immune component in various types of in vitro human organoid systems to recapitulate normal and pathological development. However, to date, generation of human alveolar organoids (AOs) containing macrophages for use as a pulmonary fibrosis (PF) model and drug efficacy evaluation has not been reported. Here, we generated multicellular alveolar organoids (Mac-AOs) containing functional macrophages derived from human pluripotent stem cells based on stepwise direct differentiation by mimicking developmental cues in a temporally controlled manner. Derived Mac-AOs contained the expected range of cell types, including alveolar progenitors, mesenchymal cells, alveolar epithelial cells (type 1 and 2), and macrophages. Treatment with transforming growth factor (TGF-β1) induced inflammation and fibrotic changes in Mac-AOs, offering a PF model for validating the therapeutic potential of new drugs. TGF-β1-induced fibrotic responses and collagen accumulation in these Mac-AOs were effectively ameliorated by treatment with Pirfenidone, Nintedanib, and NP-011 via suppression of extracellular signal-regulated kinase signaling. To the best of our knowledge, this is the first report to provide non-epithelial functional macrophage-containing human AO system, which will better recapitulate the complexity of in vivo alveolar tissues and advance our understanding of the pathogenesis and development of effective therapies for PF.
Validating the family coping questionnaire for eating disorders for caregivers of Japanese patients with eating disorders: association between coping strategies and psychological characteristics
Authors: Miyamoto Seraki , Harashima Saki , Yoshiuchi Kazuhiro
Published: December 2021

Background

Eating disorders (ED) can adversely affect the psychological health of patients’ caregivers. The present study aimed to validate a Japanese version of the Family Coping Questionnaire for Eating Disorders (FCQ-ED-J) and investigate the association between the coping strategies and psychological states of the caregivers of ED patients.

Methods

The caregivers completed the FCQ-ED-J and the Profile of Mood States. The FCQ-ED measures the coping strategies of caregivers of ED patients to the ED symptom-related behaviors. As confirmatory factor analysis did not yield an adequate model fit, the factor structure of the FCQ-ED-J was analyzed using exploratory factor analysis. Subsequently, the reliability and validity of the FCQ-ED-J were examined using Cronbach’s alpha and Pearson’s correlation coefficients in relation to the Profile of Mood States.

Results

Data from 150 caregivers, including 91 mothers and 34 fathers, was analyzed (mean age 51.1 years, SD = 12.0). The FCQ-ED-J, with 13 items grouped across four subscales [“response to binge-eating” (factor 1), “response to frequent weighing” (factor 2), “response to too much physical exercise” (factor 3), and “response to abusing laxatives and/or diuretics” (factor 4)] had Cronbach’s alpha values representing acceptable to good internal consistency (0.71–0.85). Each subscale of the FCQ-ED-J was significantly correlated with the Profile of Mood States subscales.

Conclusions

The FCQ-ED-J had sufficient reliability and validity. The Japanese caregivers’ responses to the patient’s ED symptom-related behavior were associated with their psychological states. Thus, the FCQ-ED-J may offer insight into more effective and reasonable care by caregivers for ED patients.

Plain English summary

The Family Coping Questionnaire has been used by researchers to assess the coping strategies of the relatives of patients. The present study aimed to validate a Japanese version of the Family Coping Questionnaire for Eating Disorders (FCQ-ED-J) and investigate the association between the coping strategies and psychological states of the caregivers of ED patients. Data from 150 caregivers, including 91 mothers and 34 fathers, were analyzed. The FCQ-ED-J comprised 13 items grouped into four subscales, with acceptable to good internal consistency (Cronbach’s alpha values between 0.71 and 0.85). All subscales of the FCQ-ED-J were found to be statistically significantly correlated with the profile of mood states (POMS) subscales. The Japanese caregivers’ responses to the patient’s ED symptom-related behavior were associated with their psychological states. Thus, the FCQ-ED-J can be utilized to help caregivers provide more effective and reasonable psychological care and support to ED patients.
A comparison of the 33-item Hypomania Checklist with the 33-item Hypomania Checklist-external assessment for the detection of bipolar disorder in adolescents
Authors: Chen Xu , Bai Wei , Zhao Na , Sha Sha , Cheung Teris , Ungvari Gabor S. , Feng Yuan , Xiang Yu-Tao , Angst Jules
Published: December 2021

Background

Adolescents with bipolar disorder (BD) are often misdiagnosed as having major depressive disorder (MDD), which delays appropriate treatment and leads to adverse outcomes. The aim of this study was to compare the performance of the 33-item Hypomania Checklist (HCL-33) with the 33-item Hypomania Checklist- external assessment (HCL-33-EA) in adolescents with BD or MDD.

Methods

147 adolescents with BD and 113 adolescents with MDD were consecutively recruited. The HCL-33 and HCL-33-EA were completed by patients and their carers, respectively. The sensitivity, positive predictive value (PPV), specificity, negative predictive value (NPV), and area under the curve (AUC) were calculated and compared between the two instruments, using cut-off values based on the Youden’s index.

Results

The total scores of the HCL-33 and HCL-33-EA were positively and significantly correlated (rs = 0.309, P < 0.001). Compared to the HCL-33, the HCL-33-EA had higher sensitivity and NPV (HCL-33: sensitivity = 0.58, NPV = 0.53; HCL-33-EA: sensitivity = 0.81, NPV = 0.60), while the HCL-33 had higher specificity and PPV (HCL-33: specificity = 0.61, PPV = 0.66; HCL-33-EA: specificity = 0.37, PPV = 0.63).

Conclusion

Both the HCL-33 and HCL-33-EA seem to be useful for screening depressed adolescents for BD. The HCL-33-EA would be more appropriate for distinguishing BD from MDD in adolescents due to its high sensitivity in Chinese clinical settings.
Market conditions of international VET providers: a comparative analysis of Australia, UK, USA, and Germany
Authors: Peters Susanne
Published: December 2021

VET (vocational education and training) is a highly complex, multidimensional worldwide phenomenon with diverse structures. Additionally, very different actors define the functions of a national (or even a regional) VET system. The paper contributes to a better understanding of the policy frameworks and current states of such systems. Therefore, we focus on selected VET systems in order to understand their specifics and thus, their market conditions. A qualitative approach is used to answer the research question regarding which conditions create or support market-based opportunities for the provision of commercial vocational training services. We find that the liberalism and deregulation of the VET sectors, as well as the marketisation of VET practices, lead to incentives to internationalise VET offers. Thinking in terms of skills, the kind of education system does not play a role. This is the case in liberal market-driven VET approaches (here, the UK, the USA and Australia) and is mirrored in the micro-analysis categories of curricula, learning location, content, and learning process.
De novo pathogenic variant in SETX causes a rapidly progressive neurodegenerative disorder of early childhood-onset with severe axonal polyneuropathy
Authors: Hadjinicolaou Aristides , Ngo Kathie J. , Conway Daniel Y. , Provias John P. , Baker Steven K. , Brady Lauren I. , Bennett Craig L. , La Spada Albert R. , Fogel Brent L. , Yoon Grace
Published: December 2021

Pathogenic variants in SETX cause two distinct neurological diseases, a loss-of-function recessive disorder, ataxia with oculomotor apraxia type 2 (AOA2), and a dominant gain-of-function motor neuron disorder, amyotrophic lateral sclerosis type 4 (ALS4). We identified two unrelated patients with the same de novo c.23C > T (p.Thr8Met) variant in SETX presenting with an early-onset, severe polyneuropathy. As rare private gene variation is often difficult to link to genetic neurological disease by DNA sequence alone, we used transcriptional network analysis to functionally validate these patients with severe de novo SETX-related neurodegenerative disorder. Weighted gene co-expression network analysis (WGCNA) was used to identify disease-associated modules from two different ALS4 mouse models and compared to confirmed ALS4 patient data to derive an ALS4-specific transcriptional signature. WGCNA of whole blood RNA-sequencing data from a patient with the p.Thr8Met SETX variant was compared to ALS4 and control patients to determine if this signature could be used to identify affected patients. WGCNA identified overlapping disease-associated modules in ALS4 mouse model data and ALS4 patient data. Mouse ALS4 disease-associated modules were not associated with AOA2 disease modules, confirming distinct disease-specific signatures. The expression profile of a patient carrying the c.23C > T (p.Thr8Met) variant was significantly associated with the human and mouse ALS4 signature, confirming the relationship between this SETX variant and disease. The similar clinical presentations of the two unrelated patients with the same de novo p.Thr8Met variant and the functional data provide strong evidence that the p.Thr8Met variant is pathogenic. The distinct phenotype expands the clinical spectrum of SETX-related disorders.
Floral organ-specific proteome profiling of the floral ornamental orchid (Cymbidium goeringii) reveals candidate proteins related to floral organ development
Authors: Chen Yue , Xu Zihan , Shen Qi , Sun Chongbo
Published: December 2021

Background

Cymbidium goeringii, belonging to the Orchidaceae family, is an important ornamental plant with striking petals and lips. Extremely diversified floral patterns and morphologies make C. goeringii good research material to examine floral development of orchids. However, no floral organ-specific protein has been identified yet. To screen floral development associated proteins, four proteomes from petal (PE), lip (LI), gynostemium (GY), and sepal (SE) were analyzed using Tandem Mass Tag-based proteomic analysis.

Results

A total of 6626 unique peptides encoding 2331 proteins were identified in our study. Proteins in several primary metabolic pathways, including amino acid metabolism, energy metabolism, and lipid metabolism, were identified as differentially expressed proteins. Interestingly, most of the energy metabolism-related proteins highly expressed in SE, indicating that SE is an important photosynthetic organ of C. goeringii flower. Furthermore, a number of phytohormone-related proteins and transcription factors (TFs) were identified in C. goeringii flowers. Expression analysis showed that 1-aminocyclopropane-1-carboxylate oxidase highly expressed in GY, IAA-amino acid hydrolase ILR1-like 4 and gibberellin receptor 1 C greatly expressed in LI, and auxin-binding protein ABP20 significantly expressed in SE, suggesting a significant role of hormones in the regulation of flower morphogenesis and development. For TFs, GY-highly expressed bHLH13, PE-highly expressed WRKY33, and GY-highly expressed VIP1, were identified.

Conclusions

Mining of floral organ differential expressed enzymes and TFs helps us to excavate candidate proteins related to floral organ development and to accelerate the breeding of Cymbidium plants.
A new theoretical understanding of big data analytics capabilities in organizations: a thematic analysis
Authors: Sabharwal Renu , Miah Shah Jahan
Published: December 2021

Big Data Analytics (BDA) usage in the industry has been increased markedly in recent years. As a data-driven tool to facilitate informed decision-making, the need for BDA capability in organizations is recognized, but few studies have communicated an understanding of BDA capabilities in a way that can enhance our theoretical knowledge of using BDA in the organizational domain. Big Data has been defined in various ways and, the past literature about the classification of BDA and its capabilities is explored in this research. We conducted a literature review using PRISMA methodology and integrated a thematic analysis using NVIVO12. By adopting five steps of the PRISMA framework—70 sample articles, we generate five themes, which are informed through organization development theory, and develop a novel empirical research model, which we submit for validity assessment. Our findings improve effectiveness and enhance the usage of BDA applications in various Organizations.
Hydrocortisone, ascorbic acid, and thiamine (HAT) for sepsis and septic shock: a meta-analysis with sequential trial analysis
Authors: Na Weilan , Shen Huili , Li Yichu , Qu Dong
Published: December 2021

Background

Sepsis is a primary global health threat and costs a lot, requiring effective and affordable treatments. We performed this meta-analysis to explore the treatment of hydrocortisone, ascorbic acid, and thiamine (HAT) in sepsis and septic shock.

Methods

We searched Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception to August 14, 2021. We included randomized controlled trials (RCTs) that evaluated the HAT treatments in sepsis and septic shock. The primary outcome was the change in SOFA score over the 72 h. The second outcomes were the hospital, and 28-/30-day mortality, the duration of vasopressors, PCT clearance, hospital length of stay (LOS), and ICU LOS. We performed a subgroup analysis and a trial sequential analysis (TSA). The Der Simonian–Laird random-effects models were used to report the pooled risk ratios (RR) or mean difference (MD) with confidence intervals (CI).

Results

Nine RCTs, enrolling 1427 patients of sepsis and septic shock treated with HAT (717) or only standard care (710), were included. There was a significant difference between the two groups in the change in SOFA score over the first 72 h (MD 0.65, 95% CI 0.30 to 1.00), the duration of vasopressors (MD − 18.16, 95% CI − 25.65 to − 10.68) and the PCT clearance (MD 14.54, 95% CI 0.64 to 28.43). In addition, there was no significant difference in the hospital mortality (RR 1.07, 95% CI 0.85 to 1.34), the 28-/30-day mortality (RR 0.96, 95% CI 0.80 to 1.15), the hospital LOS (MD 0.78, 95% CI − 0.30 to 1.86), and ICU LOS (MD 0.12, 95% CI − 0.53 to 0.78).

Conclusions

The HAT combination improves the SOFA score in the first 72 h and reduces the duration of vasopressors in patients with sepsis. Given the minor mean difference of the change in SOFA score, the mortality benefit has not been observed.

Trial registration

PROSPERO, CRD42020203166.
Colonic metastasis of hepatocellular carcinoma with repeated retroperitoneal bleeding: a case report
Authors: Miyauchi Wataru , Yamamoto Manabu , Masahiro Makinoya , Shishido Yuji , Miyatani Kozo , Matsunaga Tomoyuki , Sakamoto Teruhisa , Fujiwara Yoshiyuki
Published: December 2021

Background

Colonic metastasis is uncommon in patients with hepatocellular carcinoma (HCC). In the past, extrahepatic metastasis of HCC was not treated aggressively because of its poor prognosis. Herein, we describe the case of a patient with HCC who survived for 30 months following resection of a metastatic tumor in the ascending colon.

Case presentation

An 80-year-old man presented at our hospital with symptoms of abdominal pain on the right side and fever. He had undergone transcatheter arterial chemoembolization and posterior segment resection of the liver because of HCC, followed by radiofrequency ablation for a recurrent intrahepatic lesion 5 and 3 years, respectively, prior to the visit. He was diagnosed with retroperitoneal hematoma, which was thought to be associated with diverticulitis and an extramural tumor in the ascending colon. A definitive diagnosis could not be reached; however, a right hemicolectomy of the colon was performed because of progression to anemia. A pathological examination revealed a metastatic tumor in the ascending colon extending from the subserosal layer to the muscularis propria layer. The patient was treated with lenvatinib after surgery, but presented with intrahepatic recurrence, lymph node metastasis, and peritoneal dissemination metastasis 15 months later. The progression of the disease could not be controlled and his postoperative survival time was 30 months.

Conclusion

Resection of metastasis of HCC might contribute to prolonged survival in cases, where radical resection is possible.