bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel immune subtype classification of ER-positive, PR-negative and HER2-negative breast cancer based on the genomic and transcriptomic landscape
Authors: Xie Peiling , An Rui , Yu Shibo , He Jianjun , Zhang Huimin 
Published: September 2021

Abstract
Background
The diversity and plasticity behind ER+/PR−/HER2− breast cancer have not been widely explored. It is essential to identify heterogeneous microenvironment phenotypes and investigate specific genomic events driving the formation of these phenotypes.

Methods
Based on the immune-related gene expression profiles of 411 ER+/PR−/HER2− breast cancers in the METABRIC cohort, we used consensus clustering to identify heterogeneous immune subtypes and assessed their reproducibility in an independent meta-cohort including 135 patients collected from GEO database. We further analyzed the differences of cellular and molecular characteristics, and potential immune escape mechanism among immune subtypes. In addition, we constructed a transcriptional trajectory to visualize the distribution of individual patient.

Results
Our analysis identified and validated five reproducible immune subtypes with distinct cellular and molecular characteristics, potential immune escape mechanisms, genomic drivers, as well as clinical outcomes. An immune-cold subtype, with the least amount of lymphocyte infiltration, had a poorer prognosis. By contrast, an immune-hot subtype, which demonstrated the highest infiltration of CD8+ T cells, DCs and NK cells, and elevated IFN-γ response, had a comparatively favorable prognosis. Other subtypes showed more diverse gene expression and immune infiltration patterns with distinct clinical outcomes. Finally, our analysis revealed a complex immune landscape consisting of both discrete cluster and continuous spectrum.

Conclusion
Overall, this study revealed five heterogeneous immune subtypes among ER+/PR–/HER2− breast cancer, also provided important implications for clinical translations.
Tauroursodeoxycholic acid alleviates secondary injury in spinal cord injury mice by reducing oxidative stress, apoptosis, and inflammatory response
Authors: Hou Yonghui , Luan Jiyao , Huang Taida , Deng Tiancheng , Li Xing , Xiao Zhifeng , Zhan Jiheng , Luo Dan , Hou Yu , Xu Liangliang , Lin Dingkun 
Published: September 2021

Abstract
Background
Tauroursodeoxycholic acid (TUDCA) is a hydrophilic bile acid derivative, which has been demonstrated to have neuroprotective effects in different neurological disease models. However, the effect and underlying mechanism of TUDCA on spinal cord injury (SCI) have not been fully elucidated. This study aims to investigate the protective effects of TUDCA in the SCI mouse model and the related mechanism involved.

Methods
The primary cortical neurons were isolated from E16.5 C57BL/6 mouse embryos. To evaluate the effect of TUDCA on axon degeneration induced by oxidative stress in vitro, the cortical neurons were treated with H2O2 with or without TUDCA added and immunostained with Tuj1. Mice were randomly divided into sham, SCI, and SCI+TUDCA groups. SCI model was induced using a pneumatic impact device at T9-T10 level of the vertebra. TUDCA (200 mg/kg) or an equal volume of saline was intragastrically administrated daily post-injury for 14 days.

Results
We found that TUDCA attenuated axon degeneration induced by H2O2 treatment and protected primary cortical neurons from oxidative stress in vitro. In vivo, TUDCA treatment significantly reduced tissue injury, oxidative stress, inflammatory response, and apoptosis and promoted axon regeneration and remyelination in the lesion site of the spinal cord of SCI mice. The functional recovery test revealed that TUDCA treatment significantly ameliorated the recovery of limb function.

Conclusions
TUDCA treatment can alleviate secondary injury and promote functional recovery by reducing oxidative stress, inflammatory response, and apoptosis induced by primary injury, and promote axon regeneration and remyelination, which could be used as a potential therapy for human SCI recovery.
Preparing for and responding to sexual and reproductive health in disaster settings: evidence from Fiji and Tonga
Authors: Beek Kristen , Drysdale Robyn , Kusen Matthew , Dawson Angela 
Published: September 2021

Abstract
Background
Pacific Island countries are vulnerable to disasters, including cyclones and earthquakes. Disaster preparedness is key to a well-coordinated response to preventing sexual violence and assisting survivors, reducing the transmission of HIV and other STIs, and preventing excess maternal and neonatal mortality and morbidity. This study aimed to identify the capacity development activities undertaken as part of the SPRINT program in Fiji and Tonga and how these enabled the sexual and reproductive health (SRH) response to Tropical Cyclones Winston and Gita.

Methods
This descriptive qualitative study was informed by a framework designed to assess public health emergency response capacity across various levels (systems, organisational, and individual) and two phases of the disaster management cycle (preparedness and response). Eight key informants were recruited purposively to include diverse individuals from relevant organisations and interviewed by telephone, Zoom, Skype and email. Template analysis was used to examine the data.

Findings
Differences in the country contexts were highlighted. The existing program of training in Tonga, investment from the International Planned Parenthood Federation (IPPF) Humanitarian Hub, the status of the Tonga Family Health Association as the key player in the delivery of SRH, together with its long experience of delivering contract work in short time-frames and strong relationship with the Ministry of Health (MoH) facilitated a relatively smooth and rapid response. In contrast, there had been limited capacity development work in Fiji prior to Winston, requiring training to be rapidly delivered during the immediate response to the cyclone with the support of surge staff from IPPF. In Fiji, the response was initially hampered by a lack of clarity concerning stakeholder roles and coordination, but linkages were quickly built to enable a response. Participants highlighted the importance of personal relationships, individuals’ and organisations' motivation to respond, and strong rapport with the community to deliver SRH.

Discussion
This study highlights the need for comprehensive activities at multiple levels within a country and across the Pacific region to build capacity for a SRH response. While the SPRINT initiative has been implemented across several regions to improve organisational and national capacity preparedness, training for communities can be strengthened. This research outlines the importance of formalising partnerships and regular meetings and training to ensure the currency of coordination efforts in readiness for activation. However, work is needed to further institutionalise SRH in emergencies in national policy and accountability mechanisms.
Risky business: COVAX and the financialization of global vaccine equity
Authors: Stein Felix 
Published: September 2021

Abstract
Background
During the first year and a half of the COVID-19 pandemic, COVAX has been the world’s most prominent effort to ensure equitable access to SARS-CoV-2 vaccines. Launched as part of the Access to COVID-19 Tools Accelerator (Act-A) in June 2020, COVAX suggested to serve as a vaccine buyers’ and distribution club for countries around the world. It also aimed to support the pharmaceutical industry in speeding up and broadening vaccine development. While COVAX has recently come under critique for failing to bring about global vaccine equity, influential politicians and public health advocates insist that future iterations of it will improve pandemic preparedness. So far COVAX’s role in the ongoing financialization of global health, i.e. in the rise of financial concepts, motives, practices and institutions has not been analyzed.

Methods
This article describes and critically assesses COVAX’s financial logics, i.e. the concepts, arguments and financing flows on which COVAX relies. It is based on a review of over 109 COVAX related reports, ten in-depth interviews with global health experts working either in or with COVAX, as well as participant observation in 18 webinars and online meetings concerned with global pandemic financing, between September 2020 and August 2021.

Results
The article finds that COVAX expands the scale and scope of financial instruments in global health governance, and that this is done by conflating different understandings of risk. Specifically, COVAX conflates public health risk and corporate financial risk, leading it to privilege concerns of pharmaceutical companies over those of most participating countries – especially low and lower-middle income countries (LICs and LMICs). COVAX thus drives the financialization of global health and ends up constituting a risk itself - that of perpetuating the downsides of financialization (e.g. heightened inequality, secrecy, complexity in governance, an ineffective and slow use of aid), whilst insufficiently realising its potential benefits (pandemic risk reduction, increased public access to emergency funding, indirect price control over essential goods and services).

Conclusion
Future iterations of vaccine buyers’ and distribution clubs as well as public vaccine development efforts should work towards reducing all aspects of public health risk rather than privileging its corporate financial aspects. This will include reassessing the interplay of aid and corporate subsidies in global health.
The feasibility of a dose painting procedure to treat prostate cancer based on mpMR images and hierarchical clustering
Authors: Rezaeijo Seyed Masoud , Hashemi Bijan , Mofid Bahram , Bakhshandeh Mohsen , Mahdavi Arash , Hashemi Mohammad Saber 
Published: September 2021

AbstractBackgroundWe aimed to assess the feasibility of a dose painting (DP) procedure, known as simultaneous integrated boost intensity modulated radiation Therapy (SIB-IMRT), for treating prostate cancer with dominant intraprostatic lesions (DILs) based on multi-parametric magnetic resonance (mpMR) images and hierarchical clustering with a machine learning technique.MethodsThe mpMR images of 120 patients were used to create hierarchical clustering and draw a dendrogram. Three clusters were selected for performing agglomerative clustering. Then, the DIL acquired from the mpMR images of 20 patients were categorized into three groups to have them treated with a DP procedure being composed of three planning target volumes (PTVs) determined as PTV1, PTV2, and PTV3 in treatment plans. The DP procedure was carried out on the patients wherein a total dose of 80, 85 and 91 Gy were delivered to the PTV1, PTV2, and PTV3, respectively. Dosimetric and radiobiologic parameters [Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP)] of the DP procedure were compared with those of the conventional IMRT and Three-Dimensional Conformal Radiation Therapy (3DCRT) procedures carried out on another group of 20 patients. A post-treatment follow-up was also made four months after the radiotherapy procedures.ResultsAll the dosimetric variables and the NTCPs of the organs at risks (OARs) revealed no significant difference between the DP and IMRT procedures. Regarding the TCP of three investigated PTVs, significant differences were observed between the DP versus IMRT and also DP versus 3DCRT procedures. At post-treatment follow-up, the DIL volumes and apparent diffusion coefficient (ADC) values in the DP group differed significantly (p-value < 0.001) from those of the IMRT. However, the whole prostate ADC and prostate-specific antigen (PSA) indicated no significant difference (p-value > 0.05) between the DP versus IMRT.ConclusionsThe results of this comprehensive clinical trial illustrated the feasibility of our DP procedure for treating prostate cancer based on mpMR images validated with acquired patients’ dosimetric and radiobiologic assessment and their follow-ups. This study confirms significant potential of the proposed DP procedure as a promising treatment planning to achieve effective dose escalation and treatment for prostate cancer.Trial registration: IRCT20181006041257N1; Iranian Registry of Clinical Trials, Registered: 23 October 2019,https://en.irct.ir/trial/34305.
The correlation between the labrum size and the labral tear in asymptomatic volunteers and symptomatic patients
Authors: Gao Guanying , Fu Qiang , Wu Ruiqi , Liu Rongge , Ao Yingfang , Xu Yan 
Published: September 2021

Abstract
Background
Some studies have proved that labrum size is associated with symptoms in patients with hip labral tear. The correlation between the labrum size and the labral tear in asymptomatic volunteers and symptomatic patients is still uncertain.

Methods
The volunteers with no history of pain, injury, or surgery were recruited from the community. Patients who were diagnosed with labral tear and underwent hip arthroscopic surgery in this period in our hospital were also included. The length and height of the acetabular hip labrum were measured at three separate anatomic sites through magnetic resonance imaging (MRI) along the acetabular rim: lateral, anterior, and anteroinferior.

Results
A total of 70 volunteers (125 hips) and 70 patients (70 hips) were included in this study. Sixty-six (52.8%) hips had labral tears in all 125 hips of volunteers. The lateral labral length of volunteers with labral tears was significantly larger than those without labral tears (P < .05). In 14 volunteers with unilateral labral tears, length of lateral, anterior, and anteroinferior labrum in the side with tear were significantly larger than normal on the other side. The anterior labral height of volunteers was significantly larger than that of patients (P < .05).

Conclusions
In conclusion, asymptomatic volunteers with larger length of lateral, anterior, and anteroinferior labrum are more prone to present with labral tears. Symptomatic patients with labral tears exhibited thinner anterior labrum. Further studies are warranted to explore the mechanisms of labral tears in asymptomatic people and validate the use of labral size as a guide to differential diagnosis and treatment.
A cancer-unique glycan: de-N-acetyl polysialic acid (dPSA) linked to cell surface nucleolin depends on re-expression of the fetal polysialyltransferase ST8SIA2 gene
Authors: Moe Gregory R. , Steirer Lindsay M. , Lee Joshua A. , Shivakumar Adarsha , Bolanos Alejandro D. 
Published: September 2021

AbstractBackgroundPolysialic acid (polySia) modifies six cell surface proteins in humans mainly during fetal development and some blood cells in adults. Two genes in humans,ST8SIA2andST8SIA4, code for polysialyltransferases that synthesize polySia.ST8SIA2is highly expressed during fetal development and in cancer but not in adult normal human cells.ST8SIA4is expressed in fetal and adult brain, spleen, thymus, and peripheral blood leukocytes and in cancer. We identified a derivative of polySia containing de-N-acetyl neuraminic acid residues (dPSA), which is expressed on the cell surface of human cancer cell lines and tumors but not normal cells.MethodsdPSA-modified proteins in several human cancer cell lines and normal blood cells were identified using co-immunoprecipitation with anti-dPSA antibodies, mass spectroscopy and Western blot. RNAi and CRISPR were used to knockdown and knockout, respectively, the polysialyltransferase genes in human melanoma SK-MEL-28 and neuroblastoma CHP-134 cell lines, respectively, to determine the effect on production of cell surface dPSA measured by flow cytometry and fluorescence microscopy.ResultsWe found that dPSA is linked to or associated with nucleolin, a nuclear protein reported to be on the cell surface of cancer but not normal cells. Knocking down expression ofST8SIA2with RNAi or knocking out each gene individually and in combination using CRISPR showed that cell surface dPSA depended on expression ofST8SIA2.ConclusionsThe presence of dPSA specifically in a broad range of human cancers but not human adult normal cells offers novel possibilities for diagnosis, prevention and treatment targeting the dPSA antigen that appears to be cancer-specific, consistent across not only human cancers but also species, and may be an unrecognized mechanism of immune shielding.
LightGBM: accelerated genomically designed crop breeding through ensemble learning
Authors: Yan Jun , Xu Yuetong , Cheng Qian , Jiang Shuqin , Wang Qian , Xiao Yingjie , Ma Chuang , Yan Jianbing , Wang Xiangfeng 
Published: September 2021

AbstractLightGBM is an ensemble model of decision trees for classification and regression prediction. We demonstrate its utility in genomic selection-assisted breeding with a large dataset of inbred and hybrid maize lines. LightGBM exhibits superior performance in terms of prediction precision, model stability, and computing efficiency through a series of benchmark tests. We also assess the factors that are essential to ensure the best performance of genomic selection prediction by taking complex scenarios in crop hybrid breeding into account. LightGBM has been implemented as a toolbox, CropGBM, encompassing multiple novel functions and analytical modules to facilitate genomically designed breeding in crops.
Scrotal wall leiomyosarcoma: a case report and review of the literature
Authors: Erfani Zahra , Azari-yam Aileen , Yahyazadeh Seyed Reza 
Published: September 2021

Abstract
Background
Up to 30% of all scrotal masses are sarcomas. Leiomyosarcoma of the scrotal wall is rare, and its clinical significance and prognosis have not been well defined, since the most reported cases have little or no follow-up.

Case presentation
We report a 45-year-old Caucasian man who was admitted with a firm, nontender, mobile scrotal wall mass from 15 months ago. Laboratory data including testicular tumor markers were within normal range, and transscrotal ultrasonography revealed an oval-shaped, hypoechogenic, solid mass with blood flow and well-defined border. Histopathologic examination and immunohistochemistry staining, following surgical excision, were in favor of malignant leiomyosarcoma.

Conclusion
Here we describe the morphological features and immunohistochemical presentations of the tumor and the patient’s relatively long-term follow-up.
Failure of Israeli pediatric residency curricula to cover child development and special education issues: results of a national survey on levels of knowledge
Authors: Tokatly Latzer Itay , Grossman Zachi , Sachs Nimrod , Yahal Orr , Even-Zohar Daniel , Carmon Lior , Flor-Hirsch Hadar , Ringel Amit , Farah Christopher Fady , Avni-Maskit Moran , Leitner Yael 
Published: September 2021

Abstract
Background
There is an increasing prevalence of developmental difficulties among Israeli children. We aimed to assess whether pediatricians are equipped to diagnose and manage them.

Methods
We assessed the knowledge of basic child development issues and availability of services and content of special education systems among a randomly selected national sample of residents and senior Israeli pediatricians. This was done via an 70-itemed survey developed especially for this study which consisted of seven main subjects: developmental milestones, global developmental delay, autism spectrum disorder, attention deficit hyperactivity disorder, protocol for referring to a child development institute, availability and facilities of special education systems, and medical conditions associated with developmental delay.

Results
A total of 310 pediatricians (an 86 % usable response rate) participated. The total median knowledge score was 32.1 % (IQR 17.8–53.5 %). Knowledge was significantly better among senior pediatricians (p < .001), those working in an office-based setting (p < .001), and those who were parents (p < .001) or had a family history of a developmental condition (p = .003). Most responders (94 %) felt that their resident training in child development was inadequate, and that they do not have sufficient access to resources and guidelines about child development and special education systems (80 %).

Conclusions
The gap in knowledge on topics of child development and special education systems among Israeli pediatricians stems from inadequacies in the current curricula of pediatric residencies. The alarmingly low scores of our survey on these issues call for prompt revamping of the syllabus to include them.
Autoinflammation leading to autoimmunity in adult-onset Still’s disease: more than simple coincidence?
Authors: Valor-Méndez Larissa , Manger Bernhard , Cavallaro Alexander , Achenbach Stephan , Schett Georg , Rech Jürgen 
Published: September 2021

Abstract
Background
Adult-onset Still’s disease (AOSD) should be considered in the differential diagnosis of patients with endocarditis, with or without a cardiac decompensation.

Case presentation
We report the case of a 68-year-old Caucasian male diagnosed with AOSD after an initial acute manifestation of endocarditis with severe aortic acute manifestation of endocarditis with severe aortic insufficiency. The histological findings revealed Libman–Sacks endocarditis. He was treated with the IL-1 receptor inhibitor anakinra. Two years later the patient developed a symptomatic dilated cardiomyopathy with reduced ejection fraction (23.5%) and functional anti-beta-1-adrenergic receptor antibodies, which was initially treated with plasmapheresis; anakinra was maintained. While his AOSD symptoms responded well, our patient presented with recurrent arthritis in multiple joints, dual-energy CT showed urate deposition compatible with a gouty arthropathy. Over 7 years, he presented with recurrent episodes of arthritis and the adjustment of dosages of colchicine and febuxostat was needed. In 2018, our patient died due to a deterioration of his underlying cardiac disease.

Conclusions
Only two cases with initial endocarditis prior to AOSD diagnosis have been published, and we are not aware of any other cases reporting -β1AR-Ab development with DCM and gout in the setting of AOSD treated with anakinra.
30-day readmission rate in pediatric otorhinolaryngology inpatients: A retrospective population-based cohort study
Authors: Geißler Katharina , Rippe Wido , Boeger Daniel , Buentzel Jens , Hoffmann Kerstin , Kaftan Holger , Mueller Andreas , Radtke Gerald , Guntinas-Lichius Orlando 
Published: September 2021

Objectives Analysis of frequency and reasons for planned and unplanned 30-day readmission in hospitalized pediatric otorhinolaryngology patients using German Diagnosis Related Group (G-DRG) system data. Methods A retrospective population-based cohort study in Thuringia, Germany, was performed for the year 2015 with 2440 cases under 18 years (55.6% male) out of a total number of 15.271 inpatient cases. The majority of pediatric patients were from 2 to 5 years old (54.5%). The most frequent diagnoses were hyperplasia of adenoids or/and tonsils (26.6%). 36 cases (1.5%) experienced readmission within 30-days. Results 30-day readmission was planned in 9 cases (25% of all readmission) and was unplanned in 27 cases (75%). The median interval between index and readmission treatment was 8 days. Postoperative bleeding after adenoidectomy, tonsillotomy/tonsillectomy or tracheostomy (33.4%) and infectious complications after surgery like acute otitis media, abscess formation or fever (36.2%) were the most frequent reasons for 30-day readmission. Compared to adults treated in 2015 in Thuringia, the readmission rate was higher in adult patients (8.9%) than in this pediatric cohort. In contrast to children, readmissions in adults were mainly planned (65.1%) with a different spectrum of underlying diseases and reasons for readmission. Conclusion The 30-day readmission rate seemed to be lower for pediatric otolaryngology patients compared to adult patients. Unplanned readmissions dominated in pediatric patients, whereas planned readmissions dominated in adults.