bluuebunny/crossref_metadata_2025_split huggingface dataset:
CYB561D2 up-regulation activates STAT3 to induce immunosuppression and aggression in gliomas
Authors: Tao Bangbao , Shi Juanhong , Shuai Shuai , Zhou Haiyan , Zhang Hongxia , Li Bin , Wang Xiaoqiang , Li Guohui , He Hua , Zhong Jun 
Published: August 2021

Abstract
Background
Fine tuned balance of reactive oxygen species (ROS) is essential for tumor cells and tumor cells use immune checkpoints to evade attack form immunity system. However, it’s unclear whether there is any crosstalk between these two pathways. CYB561D2, an antioxidant protein, is part of 5-gene prognosis signature in gliomas and its involvement in gliomas is unknown. Here, we aim to provide a detailed characterization of CYB561D2 in gliomas.

Methods
CYB561D2 expression was measured in clinical samples of gilomas and normal tissues. The effects of CYB561D2 on immunity related genes and tumor behaviors were investigated in glioma cell lines with various in vitro and in vivo assays.

Results
CYB561D2 expression was enhanced in gliomas compared to control tissues. CYB561D2 up-regulation was associated with high grading of gliomas and short survival in patients. CYB561D2 expression was induced by H2O2 in glioma cell lines. CYB561D2 and its functional product ascorbate activated STAT3 dose-dependently. CYB561D2 over-expression increased PD-L1, CCL2 and TDO2 expression, and induced immunosuppression in co-cultured T cells. In in vitro assays, CYB561D2 knock-down suppressed cell growth, colony formation, migration and promoted apoptosis. In contrast, CYB561D2 over-expression reduced survival rate in intracranial glioma model and this effect could be blocked by dominant negative-STAT3. The CYB561D2 up-regulation and the positive association of CYB561D2 with PD-L1, CCL2 and TDO2 expression were cross-validated in open-access datasets.

Conclusions
CYB561D2 up-regulation induces immunosuppression and aggression via activating STAT3 in gliomas and CYB561D2 mediates ROS-tumor immunity crosstalk.
MYC: a multipurpose oncogene with prognostic and therapeutic implications in blood malignancies
Authors: Ahmadi Seyed Esmaeil , Rahimi Samira , Zarandi Bahman , Chegeni Rouzbeh , Safa Majid 
Published: August 2021

AbstractMYC oncogene is a transcription factor with a wide array of functions affecting cellular activities such as cell cycle, apoptosis, DNA damage response, and hematopoiesis. Due to the multi-functionality of MYC, its expression is regulated at multiple levels. Deregulation of this oncogene can give rise to a variety of cancers. In this review, MYC regulation and the mechanisms by which MYC adjusts cellular functions and its implication in hematologic malignancies are summarized. Further, we also discuss potential inhibitors of MYC that could be beneficial for treating hematologic malignancies.
Role of the cytopathologist during the procedure of fine-needle aspiration biopsy of thyroid nodules
Authors: Feletti F. , Mellini L. , Pironi F. , Carnevale A. , Parenti G. C. 
Published: August 2021

Abstract
Purpose
This study aimed to conduct a diagnostic and cost-effective analysis of the cytopathology assistance in the ultrasound (US)-guided fine-needle aspiration biopsy (FNAB) for characterising thyroid nodules.

Materials and methods
We reviewed the reports relative to 9061 US-guided FNABs for the histologic definition of the nature of thyroid nodules: 45.4% completed with the cytopathologist assistance and 54.6% by the radiologist alone.
We also performed the cost-effectiveness analysis (CEA) of the procedure with and without the cytopathologist assistance.

Results
We found a significant positive correlation between the adoption/non-adoption of cytopathologist assistance and the number of indeterminate (TIR1) (Chi-square; z-score, Z = 10.22; critical value 5%, C = 1.96; p < 0.001). The cytopathologist's absence was correlated with the number of TIR 1 (Pearson correlation, product–moment correlation r = 0.059; critical value 5%, C = 0.008; p < 0.001).
The total cost of the model's cytopathologist-assistance branch is 109.87€, while the total cost of the non-cytopathologist-assistance branch is 95.08€.

Conclusion
The cytopathologist assistance resulted in fewer nondiagnostic results, thus excluding the procedure's repetition but involved a higher expense, mainly due to the professional cost of the pathologist's participation. These data may provide decision-makers in healthcare with a practical evidence based on the opportunity to include the cytopathologist assistance in the thyroid nodule's FNAB depending on the available resources and the population's expectance.
Imaging in non-bacterial osteomyelitis in children and adolescents: diagnosis, differential diagnosis and follow-up—an educational review based on a literature survey and own clinical experiences
Authors: Schaal Matthias C. , Gendler Liya , Ammann Bettina , Eberhardt Nina , Janda Aleš , Morbach Henner , Darge Kassa , Girschick Hermann , Beer Meinrad 
Published: August 2021

AbstractBackgroundChronic non-bacterial osteomyelitis (CNO) is an autoinflammatory bone disorder affecting children and adolescents. Previously classified as a rare disease, recent studies suggest a higher incidence of the disease. CNO may develop into the clinical presentation of chronic recurrent osteomyelitis (CRMO) with high relapse rate and multifocality.Main bodyDiagnosis of CNO/CRMO is often delayed, with implications for disease severity and relapse rate. This can be significantly improved by knowledge of the disease entity and its characteristics. Imaging plays a key role in diagnosis, differential diagnosis and therapy monitoring. Magnetic resonance imaging (MRI) has several advantages compared to other imaging methods and is increasingly applied in clinical studies. Recent studies show that a whole-body (WB) coverage (WB-MRI) without contrast agent administration is a rational approach. This educational review is based on a systematic analysis of international peer-reviewed articles and presents our own clinical experiences. It provides an overview of disease entity, incidence and clinical diagnosis. The role of imaging, especially of whole-body MRI, is discussed in detail. Finally, practical advice for imaging, including flowcharts explaining when and how to apply imaging, is provided.ConclusionKnowing the specifics of CNO/CRMO and the importance of MRI/whole-body MRI allows rapid and efficient diagnosis as well as therapy support and helps to avoid irreversible secondary damage.
Generalized lymphatic anomalies and review of the current management landscape: a case report and review of the literature
Authors: Liu Tao , Basseri Sana , Mussari Ben , DaBreo Dominique , SenGupta Sandip , Villalobos Dalila , Awad Sara 
Published: August 2021

Abstract
Background
Generalized lymphatic anomaly previously known as diffuse systemic lymphangiomatosis is a rare multisystem congenital disease arising from the lymphatic system, and it is characterized by abnormal proliferation of the lymphatic channels in osseous and extraosseous tissues. It typically affects children or young adults. Although it is benign, it can be misdiagnosed as malignancy because of its diffuse and debilitating nature depending on the site of involvement. Due to its rarity, diagnosis is often delayed, leading to potential significant morbidity or mortality if vital organs are involved. Furthermore, its potential for multiorgan involvement with no curative treatment makes its management challenging.

Case presentation
We describe a case of a 35-year-old Caucasian female, who presented with epigastric pain and was subsequently extensively investigated at multiple tertiary centers by numerous specialists for query malignancy and metabolic bone disorder following incidental computed tomography imaging findings of multiple osteolytic lesions in the axial skeleton, and low-attenuating lesions in the axilla, spleen, and mediastinum. The diagnosis was confirmed with an axillary excisional biopsy. She was clinically stable with no end organ damage. She was monitored conservatively.

Conclusions
The case illustrates the importance of increased awareness among clinicians for this rare congenital disease to enable earlier diagnosis and to avoid unnecessary invasive investigations. Furthermore, this case highlights the potential need for multiple biopsies of affected sites to confirm diagnosis. We also discuss the emergence of interferon therapy, chemotherapy, immunosuppression, and immunotherapy as medical management for this condition.
Collagen-VI supplementation by cell transplantation improves muscle regeneration in Ullrich congenital muscular dystrophy model mice
Authors: Takenaka-Ninagawa Nana , Kim Jinsol , Zhao Mingming , Sato Masae , Jonouchi Tatsuya , Goto Megumi , Yoshioka Clémence Kiho Bourgeois , Ikeda Rukia , Harada Aya , Sato Takahiko , Ikeya Makoto , Uezumi Akiyoshi , Nakatani Masashi , Noguchi Satoru , Sakurai Hidetoshi 
Published: August 2021

Abstract
Background
Mesenchymal stromal cells (MSCs) function as supportive cells on skeletal muscle homeostasis through several secretory factors including type 6 collagen (COL6). Several mutations of COL6A1, 2, and 3 genes cause Ullrich congenital muscular dystrophy (UCMD). Skeletal muscle regeneration deficiency has been reported as a characteristic phenotype in muscle biopsy samples of human UCMD patients and UCMD model mice. However, little is known about the COL6-dependent mechanism for the occurrence and progression of the deficiency. The purpose of this study was to clarify the pathological mechanism of UCMD by supplementing COL6 through cell transplantation.

Methods
To test whether COL6 supplementation has a therapeutic effect for UCMD, in vivo and in vitro experiments were conducted using four types of MSCs: (1) healthy donors derived-primary MSCs (pMSCs), (2) MSCs derived from healthy donor induced pluripotent stem cell (iMSCs), (3) COL6-knockout iMSCs (COL6KO-iMSCs), and (4) UCMD patient-derived iMSCs (UCMD-iMSCs).

Results
All four MSC types could engraft for at least 12 weeks when transplanted into the tibialis anterior muscles of immunodeficient UCMD model (Col6a1KO) mice. COL6 protein was restored by the MSC transplantation if the MSCs were not COL6-deficient (types 1 and 2). Moreover, muscle regeneration and maturation in Col6a1KO mice were promoted with the transplantation of the COL6-producing MSCs only in the region supplemented with COL6. Skeletal muscle satellite cells derived from UCMD model mice (Col6a1KO-MuSCs) co-cultured with type 1 or 2 MSCs showed improved proliferation, differentiation, and maturation, whereas those co-cultured with type 3 or 4 MSCs did not.

Conclusions
These findings indicate that COL6 supplementation improves muscle regeneration and maturation in UCMD model mice.
Combining cell therapy with human autologous Schwann cell and bone marrow-derived mesenchymal stem cell in patients with subacute complete spinal cord injury: safety considerations and possible outcomes
Authors: Oraee-Yazdani Saeed , Akhlaghpasand Mohammadhosein , Golmohammadi Maryam , Hafizi Maryam , Zomorrod Mina Soufi , Kabir Nima Mohseni , Oraee-Yazdani Maryam , Ashrafi Farzad , Zali Alireza , Soleimani Masoud 
Published: August 2021

Abstract
Background
Cellular transplantations have promising effects on treating spinal cord injury (SCI) patients. Mesenchymal stem cells (MSCs) and Schwann cells (SCs), which have safety alongside their complementary characteristics, are suggested to be the two of the best candidates in SCI treatment. In this study, we assessed the safety and possible outcomes of intrathecal co-transplantation of autologous bone marrow MSC and SC in patients with subacute traumatic complete SCI.

Methods
Eleven patients with complete SCI (American Spinal Injury Association Impairment Scale (AIS); grade A) were enrolled in this study during the subacute period of injury. The patients received an intrathecal autologous combination of MSC and SC and were followed up for 12 months. We assessed the neurological changes by the American Spinal Injury Association’s (ASIA) sensory-motor scale, functional recovery by spinal cord independence measure (SCIM-III), and subjective changes along with adverse events (AE) with our checklist. Furthermore, electromyography (EMG), nerve conduction velocity (NCV), magnetic resonance imaging (MRI), and urodynamic study (UDS) were conducted for all the patients at the baseline, 6 months, and 1 year after the intervention.

Results
Light touch AIS score alterations were approximately the same as the pinprick changes (11.6 ± 13.1 and 12 ± 13, respectively) in 50% of the cervical and 63% of the lumbar-thoracic patients, and both were more than the motor score alterations (9.5 ± 3.3 in 75% of the cervical and 14% of the lumbar-thoracic patients). SCIM III total scores (21.2 ± 13.3) and all its sub-scores (“respiration and sphincter management” (15 ± 9.9), “mobility” (9.5 ± 13.3), and “self-care” (6 ± 1.4)) had statistically significant changes after cell injection. Our findings support that the most remarkable positive, subjective improvements were in trunk movement, equilibrium in standing/sitting position, the sensation of the bladder and rectal filling, and the ability of voluntary voiding. Our safety evaluation revealed no systemic complications, and radiological images showed no neoplastic overgrowth, syringomyelia, or pseudo-meningocele.

Conclusion
The present study showed that autologous SC and bone marrow-derived MSC transplantation at the subacute stage of SCI could reveal statistically significant improvement in sensory and neurological functions among the patients. It appears that using this combination of cells is safe and effective for clinical application to spinal cord regeneration during the subacute period.
Hypoxia preconditioned bone marrow-derived mesenchymal stromal/stem cells enhance myoblast fusion and skeletal muscle regeneration
Authors: Archacka Karolina , Grabowska Iwona , Mierzejewski Bartosz , Graffstein Joanna , Górzyńska Alicja , Krawczyk Marta , Różycka Anna M. , Kalaszczyńska Ilona , Muras Gabriela , Stremińska Władysława , Jańczyk-Ilach Katarzyna , Walczak Piotr , Janowski Mirosław , Ciemerych Maria A. , Brzoska Edyta 
Published: August 2021

Abstract
Background
The skeletal muscle reconstruction occurs thanks to unipotent stem cells, i.e., satellite cells. The satellite cells remain quiescent and localized between myofiber sarcolemma and basal lamina. They are activated in response to muscle injury, proliferate, differentiate into myoblasts, and recreate myofibers. The stem and progenitor cells support skeletal muscle regeneration, which could be disturbed by extensive damage, sarcopenia, cachexia, or genetic diseases like dystrophy. Many lines of evidence showed that the level of oxygen regulates the course of cell proliferation and differentiation.

Methods
In the present study, we analyzed hypoxia impact on human and pig bone marrow-derived mesenchymal stromal cell (MSC) and mouse myoblast proliferation, differentiation, and fusion. Moreover, the influence of the transplantation of human bone marrow-derived MSCs cultured under hypoxic conditions on skeletal muscle regeneration was studied.

Results
We showed that bone marrow-derived MSCs increased VEGF expression and improved myogenesis under hypoxic conditions in vitro. Transplantation of hypoxia preconditioned bone marrow-derived MSCs into injured muscles resulted in the improved cell engraftment and formation of new vessels.

Conclusions
We suggested that SDF-1 and VEGF secreted by hypoxia preconditioned bone marrow-derived MSCs played an essential role in cell engraftment and angiogenesis. Importantly, hypoxia preconditioned bone marrow-derived MSCs more efficiently engrafted injured muscles; however, they did not undergo myogenic differentiation.
Childhood onset exercise addiction or atypical anorexia nervosa during Covid-19: case report
Authors: McNicholas F. 
Published: August 2021

Abstract
Background
Childhood-onset Anorexia Nervosa (AN) is recognised to be atypical in presentation, both in terms of extent and nature of eating pathology, exercise and compensatory behaviours with many falling short of full diagnostic criteria. Failure to consider an eating disorder diagnosis in youth who present with extreme weight loss may have serious immediate and long term implications. However, failure to consider other non-organic causes of weight loss may be equally detrimental to the child’s health.

Case presentation
This case reports on the acute presentation of a 12-year old boy, who presented to hospital in a severely malnourished state eight weeks into lockdown. To compensate for Covid-19 induced restrictions on sporting activity, this boy had followed a self-imposed daily schedule of arduous exercise, without increasing his nutritional intake. This report examines the clinical features suggestive of AN and other differential diagnosis. A discussion on the specific diagnostic differential of exercise addiction and challenges faced by youth during Covid-19 restrictions are presented.

Conclusion
Accepting that AN may present atypically in pre-pubertal youth, it is important that clinicians maintain an open mind in youth presenting without goal directed weight loss. Although weight loss was significant in this case, it was due to an excessive exercise regime. This may have commenced as a coping strategy in response to Covid-19 restrictions but subsequently became excessive and impairing in nature. The collateral damage of Covid-19 mandated restrictions, aimed at containing the spread of the virus, are evident in this case. Clinicians need to be alert to potentially maladaptive coping strategies and unusual or altered pathways of presentation, especially in younger children during these challenging times.
Who is watching? Refugee protection during a pandemic - responses from Uganda and South Africa
Authors: Moyo Khangelani , Sebba Kalyango Ronald , Zanker Franzisca 
Published: August 2021

AbstractBoth Uganda and South Africa were quick to respond to the global pandemic – Uganda for example imposing quarantine on foreign travellers after only a handful of cases before shutting off all international flights, and South Africa imposing one of the first lockdowns on the continent. Reflecting on the first 6 months of the pandemic responses in terms of refugee protection, the two countries have taken diverging pathways. South Africa used the pandemic to start building a border fence on the border with Zimbabwe, initially curtailed all foreign shop owners from opening under lockdown and excluded asylum seekers from emergency relief grants. In contrast, Uganda opened its borders to refugees from the DRC in June, when border closures were still the global norm. Whilst both responses are not unusual in light of their standard governance approaches, they highlight the own self-image the countries espouse – with Uganda positioning itself as the world’s premier refugee protector at a time when it is desperately in need of more funds and South Africa looking to politically capitalize internally from reiterating a division between migrant communities as a threat to poor and disenfranchised South Africans. Even during a pandemic, the practice of refugee protection does not happen in a political vacuum. This paper is based on over 50 in-person and digital interviews conducted in Uganda and South Africa in 2020, as well as nine focus groups with refugee and host communities.
Immune checkpoint inhibitor-induced myocarditis in cancer patients: a case report and review of reported cases
Authors: Matzen Emma , Bartels Lars Erik , Løgstrup Brian , Horskær Stine , Stilling Christina , Donskov Frede 
Published: August 2021

Abstract
Background
Immune checkpoint inhibitor (ICI) induced myocarditis is a rare, severe, and often fatal adverse event. Evidence to guide appropriate immunosuppressive therapy is scarce. We present a case of ICI-induced myocarditis and a review of ICI-induced myocarditis cases to determine the most effective immunosuppressive therapeutic strategy for ICI-induced myocarditis.

Methods
A systematic search of PubMed was carried out for treatment of ICI-induced myocarditis. Reference lists from identified articles were manually reviewed for additional cases.

Results
A total of 87 cases with ICI-induced myocarditis were identified. The majority were melanoma (n = 39), lung cancer (n = 19), renal cell cancer (n = 10), and thymoma cancer patients (n = 4). In 38 (44%) cases, patients received high-dose steroid treatment only. A total of 49 (56%) cases were treated with immunosuppressive agents other than steroid; a total of 13 different immunosuppressive agents were used, including alemtuzumab or abatacept. The median time to onset of symptoms after initiation of ICI was 16 days (range, 1–196 days); cardiotoxic symptoms developed after 2 cycles of ICI (range, 1–13 cycles). A total of 48% of cases were fatal. In cases treated with high-dose steroids only vs. cases treated with other immunosuppressive agents, fatality was 55% and 43% respectively. In 64 out of the 87 cases, tumor control was not described. In patients treated with high-dose steroids only, two patients had stable disease as best tumor response; in patients treated with other immunosuppressive agents, one complete response, one partial response and seven stable disease were noted as best tumor response. Overall, 11 studies were at low risk of bias (12.6%), 38 at moderate risk of bias (43.7%) and 38 at high risk of bias (43.7%).

Conclusion
Immune checkpoint inhibitor induced myocarditis is a serious and often fatal adverse event. High-dose prednisolone, alemtuzumab or abatacept are all possible treatments options for ICI-induced myocarditis, whereas infliximab increases the risk of death from cardiovascular causes, and should be avoided. Further research is needed.