bluuebunny/crossref_metadata_2025_split huggingface dataset:
MegaR: an interactive R package for rapid sample classification and phenotype prediction using metagenome profiles and machine learning
Authors: Dhungel Eliza , Mreyoud Yassin , Gwak Ho-Jin , Rajeh Ahmad , Rho Mina , Ahn Tae-Hyuk 
Published: January 2021

AbstractBackgroundDiverse microbiome communities drive biogeochemical processes and evolution of animals in their ecosystems. Many microbiome projects have demonstrated the power of using metagenomics to understand the structures and factors influencing the function of the microbiomes in their environments. In order to characterize the effects from microbiome composition for human health, diseases, and even ecosystems, one must first understand the relationship of microbes and their environment in different samples. Running machine learning model with metagenomic sequencing data is encouraged for this purpose, but it is not an easy task to make an appropriate machine learning model for all diverse metagenomic datasets.ResultsWe introduce MegaR, an R Shiny package and web application, to build an unbiased machine learning model effortlessly with interactive visual analysis. The MegaR employs taxonomic profiles from either whole metagenome sequencing or 16S rRNA sequencing data to develop machine learning models and classify the samples into two or more categories. It provides various options for model fine tuning throughout the analysis pipeline such as data processing, multiple machine learning techniques, model validation, and unknown sample prediction that can be used to achieve the highest prediction accuracy possible for any given dataset while still maintaining a user-friendly experience.ConclusionsMetagenomic sample classification and phenotype prediction is important particularly when it applies to a diagnostic method for identifying and predicting microbe-related human diseases. MegaR provides various interactive visualizations for user to build an accurate machine-learning model without difficulty. Unknown sample prediction with a properly trained model using MegaR will enhance researchers to identify the sample property in a fast turnaround time.
Identification and molecular characterization of Subramaniula asteroides causing human fungal keratitis: a case report
Authors: Cultrera Rosario , Torelli Riccardo , Sarnicola Caterina , Segala Daniela , Mengoli Andrea , Chiaretto Giuseppina , Perri Paolo , Sanguinetti Maurizio 
Published: January 2021

Abstract
Background
Keratitis due to by filamentous fungi are not easy to diagnose thus causing a delay in correct therapy. There are many descriptions of keratitis due to Candida, Fusarium and Aspergillus genera. Subramaniula genus has only recently been reported to cause human infections and there are few descriptions of eye infections due to this filamentous fungus. Diagnosis of fungal keratitis is usually based on microscopic and cultural techniques of samples obtained by corneal swabbing or scraping. Considering the amount of time required to obtain culture results it is wise to use other diagnostic methods, such as molecular analyses. Therapeutic options against these fungi are limited by low tissue penetration in the eye due to ocular barriers. We describe the first case of S. asteroides human keratitis treated with isavuconazole.

Case presentation
We describe a rare case of fungal keratitis unresponsive to antimicrobial treatment in a 65-year-old male patient without a history of diabetes or immunological diseases. He reported that the onset of symptoms occurred during a long holiday in Cape Verde Island. Initial treatment with topical antibiotics associated to steroids were ineffective, allowing a slow clinical progression of disease to corneal perforation. On admission in our Hospital, slit-lamp examination of the left eye showed conjunctival congestion and hyperemia, a large inferior corneal ulceration with brown pigment, corneal edema, about 3 mm of hypopyon and irido-lenticular synechiae. The slow clinical progression of the disease to corneal perforation and the aspect of the ulcer were consistent with a mycotic etiology. Molecular methods used on fungal colonies isolated by Sabouraud’s dextrose agar cultures allowed the identification of Subramaniula asteroids from corneal scraping. Antimicrobial test showed a good susceptibility of this filamentous fungus to voriconazole and isavuconazole. Moreover, this fungal keratitis was successfully treated with isavuconazole, without side effects, observing a progressive clinical improvement.

Conclusions
Molecular methods may be useful for the identification of filamentous fungal keratitis on scraping samples thus shortening the time of diagnosis. Systemic therapy by isavuconazole could be useful to treat the filamentous fungal keratitis, reducing the possible adverse effects due to the use of voriconazole by systemic administration.
Dynamic changes in lymphocyte subsets and parallel cytokine levels in patients with severe and critical COVID-19
Authors: Liu Yangli , Tan Weiping , Chen Haihong , Zhu Ying , Wan Li , Jiang Ke , Guo Yubiao , Tang Kejing , Xie Canmao , Yi Hui , Kuang Yukun , Luo Yifeng 
Published: January 2021

Abstract
Background
The lack of knowledge regarding the pathogenesis and host immune response during SARS-CoV-2 infection has limited the development of effective treatments. Thus, we longitudinally investigated the dynamic changes in peripheral blood lymphocyte subsets and parallel changes in cytokine levels in COVID-19 patients with different disease severities to further address disease pathogenesis.

Methods
A total of 67 patients (10 moderate, 38 severe and 19 critical cases) with COVID-19 admitted to a tertiary care hospital in Wuhan from February 8th to April 6th, 2020 were retrospectively studied. Dynamic data of lymphocyte subsets and inflammatory cytokines were collected.

Results
On admission, compared with moderate cases, severe and critical cases showed significantly decreased levels of total lymphocytes, T lymphocytes, CD4+ T cells, CD8+ T cells, B cells and NK cells. IL-6 and IL-10 were significantly higher in the critical group. During the following hospitalization period, most of the lymphocyte subsets in the critical group began to recover to levels comparable to those in the severe group from the fourth week after illness onset, except for NK cells, which recovered after the sixth week. A sustained decrease in the lymphocyte subsets and an increase in IL-6 and IL-10 were observed in the nonsurvivors until death. There was a strong negative correlation between IL-6 and IL-10 and total lymphocytes, T lymphocytes, CD4+ T cells, CD8+ T cells and NK cells.

Conclusions
A sustained decrease in lymphocyte subsets, especially CD4+ T cells and NK cells, interacting with proinflammatory cytokine storms was associated with severe disease and poor prognosis in COVID-19.
A child with Imerslund-Gräsbeck syndrome concealed by co‐existing α-thalassaemia presenting with subacute combined degeneration of the spinal cord: a case report
Authors: Arunath Visvalingam , Hoole Thabitha Jebaseeli , Rathnasri Asanka , Muthukumarana Oshanie , Kumarasiri Ishara Minuri , Liyanage Nishadi Dananjani , Costa Yasintha , Mettananda Sachith 
Published: January 2021

AbstractBackgroundImerslund-Gräsbeck syndrome is a rare genetic disease characterised by vitamin B12deficiency and proteinuria.Case presentationA 4-year old Sri Lankan boy presented with gradually worsening difficulty in walking for two weeks duration. He was previously diagnosed and managed as having non-transfusion-dependent α-thalassaemia based on the presence of hypochromic microcytic anaemia, haemoglobin H inclusion bodies in the blood film and compound heterozygous α-thalassaemia genotype with a gene deletion. However, his transfusion requirement increased over the past three months and he gradually lost his motor developmental milestones during two weeks before admission. The neurological examination revealed generalised hypotonia, exaggerated knee jerks and extensor plantar response. His complete blood count showed pancytopenia, and bone marrow biopsy revealed megaloblastic changes. Serum vitamin B12and red blood cell folate levels were low. MRI revealed sub-acute combined degeneration of the spinal cord with characteristic ‘inverted V sign’. Urine analysis showed non-nephrotic range proteinuria. The diagnosis of Imerslund-Gräsbeck syndrome was made due to the presence of non-nutritional vitamin B12deficiency and asymptomatic proteinuria. He showed a rapid haematological and neurological improvement to intramuscular hydroxocobalamin.ConclusionsThis case report presents a rare occurrence of severe vitamin B12deficiency due to Imerslund-Gräsbeck syndrome masked by co-existent α-thalassaemia, resulting in serious consequences. It highlights the need for a high index of suspicion in evaluating children with severe anaemia, especially in the presence of mixed pathologies.
Unprecedented tibial bone lengthening of 33.5 cm by distraction osteogenesis for the reconstruction of a subtotal tibial bone defect. A case report and literature review
Authors: Ali Abdulnassir , Ren Ying , Zhou Chun-Hao , Fang Jia , Qin Cheng-He 
Published: January 2021

Abstract
Background
We present a case of an immense unprecedented tibial bone lengthening of 33.5 cm. The management of chronic osteomyelitis of the right tibia with subtotal tibial bone defect, talus defect and equinus ankle deformity. We demonstrate limb reconstruction by distraction osteogenesis and correction of ankle deformity with the Ilizarov technique. Limb salvage was preferred as an alternative to amputation to restore basic limb function.

Case presentation
A 16-year-old male patient fell and injured his right lower leg. He attempted to treat the symptoms with traditional home remedies. During 15 months of self-treating, he developed osteomyelitis of the right tibia and had lost function in his foot. Radiology revealed immense bone defect of the right tibia, including talus bone defect and equinus deformity of the calcaneus. The patient’s right tibia was non weight-bearing, had drainage sinus just below his knee and a large scar anteriorly along the entire length of the tibia.

Conclusion
Upon completion of treatment, the patient was able to avoid amputation of his leg with partially restored function for weight-bearing. He carried himself without assistance after 3 years of lost function in his right leg. Tibial bone distraction osteogenesis of 33.5 cm was done after 90% of the tibial length was defected. To the best of our best knowledge, this case is one of a kind to achieve distraction of tibial bone to such length.
The effect of the sagittal plane osteotomy inclination on the posterior tibial slope in medial open wedge HTO: experimental study with a square column model
Authors: Moon Sang Won , Ryu Ji Young , Lee Sung-Jae , Woo Sang Won , Park Sin Hyung , Choi Young 
Published: January 2021

AbstractBackgroundMedial open-wedge high tibial osteotomy (HTO) is an effective and safe treatment method for medial osteoarthritis of the knee. However, unintended changes in the posterior tibial slope (PTS) may occur. Several factors cause PTS alterations after medial open-wedge HTO; however, research on sagittal-plane osteotomy inclination (SPOI) in relation to the PTS is sparse. The purpose of this study was to evaluate whether the SPOI affects changes in the PTS after medial open-wedge HTO. The hypothesis was that an SPOI parallel to the PTS causes no change in the PTS after medial open-wedge HTO.MethodsA square column model with a 10° posterior slope was produced using two three-dimensional (3D) programs and a 3D printer. Then, a series of medial open-wedge HTO procedures was performed on the square column model through virtual simulation using the two 3D programs, and an actual simulation was conducted using a 3D printer, a testing machine and a measurement system. The SPOI was divided into four types: ① SPOI 20° (posterior-inclined 10° osteotomy), ② SPOI 10° (osteotomy parallel to posterior slope), ③ SPOI 0° (anterior-inclined 10° osteotomy), and ④ SPOI − 10° (anterior-inclined 20° osteotomy). The correction angle was increased at intervals of 5° from 0° to 30°. The change in posterior slope was measured in the sagittal plane.ResultsThe posterior slope was increased in SPOI 20° (posterior-inclined 10° osteotomy), maintained in SPOI 10° (osteotomy parallel to posterior slope), and decreased in SPOI 0° (anterior-inclined 10° osteotomy) and SPOI − 10° (anterior-inclined 20° osteotomy) based on the correction angle.ConclusionsIn this study using a square column model, the SPOI affected the change in the PTS, and an SPOI parallel to the PTS caused no change in the PTS after medial open-wedge HTO.
PCR-based genotyping assays to detect germline APC variant associated with hereditary gastrointestinal polyposis in Jack Russell terriers
Authors: Yoshizaki Kyoko , Hirata Akihiro , Matsushita Hiroyuki , Nishii Naohito , Kawabe Mifumi , Mori Takashi , Sakai Hiroki 
Published: January 2021

Abstract
Background
The prevalence of gastrointestinal (GI) neoplastic polyps in Jack Russell terriers (JRTs) has increased in Japan since the late 2000s. Recently, we demonstrated that JRTs with GI polyps harbor identical germline variant in the APC gene (c.[462_463delinsTT]) in the heterozygous state. Thus, this disease is an autosomal dominant hereditary disorder. Although the affected JRTs have distinct features, such as the development of multiple GI polyps and an early age of disease onset, genetic testing is indispensable for a definitive diagnosis. Here, polymerase chain reaction (PCR)-based assays capable of detecting germline APC variant were designed and validated using synthetic wild-type and mutant DNAs and genomic DNAs from carrier and non-carrier dogs.

Result
First, the PCR-restriction fragment length polymorphism (PCR-RFLP) assay was developed by taking advantage of the germline APC variant creating a new restriction site for MseI. In the PCR-RFLP assay, the 156-bp region containing the variant site was amplified by PCR and subsequently digested with MseI, yielding diagnostic 51 and 58 bp fragments from the mutant allele and allowing determination of the APC genotypes. It was possible to determine the genotypes using genomic DNA extracted from the peripheral blood, buccal swab, or formalin-fixed paraffin-embedded tissue. Next, a TaqMan duplex real-time PCR assay was developed, where a 78-bp region flanking the variant was amplified in the presence of wild-type allele- and mutant allele-specific fluorescent probes. Using blood-derived DNA, altogether 40 cycles of PCR amplification determined the APC genotypes of all examined samples by measuring the fluorescence intensities. Importantly, false-positive and false-negative errors were never detected in both assays.

Conclusion
In this study, we developed highly reliable genetic tests for hereditary GI polyposis in JRTs, providing accurate assessment of the presence of the causative germline APC variant. The genotyping assays could contribute to the diagnosis and prevention of hereditary GI polyposis in dogs.
LRIG1 expression and colorectal cancer prognosis
Authors: Bakherad Maryam , Salimi Mahdieh , Angaji Seyed Abdolhamid , Mahjoubi Frouzandeh , Majidizadeh Tayebeh 
Published: January 2021

Abstract
Background
To make the right treatment decisions about colorectal cancer (CRC) patients reliable predictive and prognostic data are needed. However, in many cases this data is not enough. Some studies suggest that LRIG1 gene (leucine-rich repeats and immunoglobulin-like domains1) has prognostic implications in different kinds of cancers.

Methods
One hundred and two patients with colorectal cancer were retrospectively analyzed for LRIG1 expression at both mRNA and protein levels. SYBR Green Real-Time RT-PCR technique was used for mRNA expression analyses and Glyceraldehyde-3-Phosphate Dehydrogenase gene (GAPDH) was considered as a reference gene for data normalization. LRIG1 protein expression was analyzed using Immunohistochemistry. Additionally, appropriate statistic analyses were used to assess the expression of LRIG1 in test and control groups. The prognostic significance of LRIG1 expression was analyzed using the univariate and multivariate analyses.

Results
The data revealed that the expression of LRIG1 in both mRNA and protein levels was down regulated in colorectal tumor tissues (P < 0.01) but is not clinically relevant prognostic indicator in CRC.

Conclusions
Therefore, it is suggested that LRIG1 expression analyses may not be considered as an important issue when making informed and individualized clinical decisions regarding the management of colorectal cancer patients.
Hereditary leiomyomatosis and renal cell carcinoma: a case series and literature review
Authors: Chayed Zahraa , Kristensen Lone Krøldrup , Ousager Lilian Bomme , Rønlund Karina , Bygum Anette 
Published: January 2021

Abstract
Background
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a rare genodermatosis characterized by cutaneous leiomyoma (CLM), uterine leiomyoma (ULM) and renal cell carcinoma (RCC). Five HLRCC patients are presented with a compiled database of published HLRCC cases to increase understanding of HLRCC. Furthermore, a surveillance program is suggested. Our review is based on a PubMed search which retrieved case reports and cohort studies published before November 2019. The search yielded 97 original papers with a total of 672 HLRCC patients.

Results
CLMs were present in 474 patients (71.5%), developed at the mean age of 28 years. Five patients had cutaneous leiomyosarcomas. ULMs were present in 356 women (83%), while two had uterine leiomyosarcoma. ULMs were diagnosed at a mean age of 32 years, with the youngest diagnosed at age 17 years. The most common surgical treatment for ULMs was hysterectomy, performed at a mean age of 35 years, with the youngest patient being 19 years old. RCCs were present in 189 patients (34.9%), of which half had metastatic disease. The mean age of diagnosis was 36 years with the youngest patient diagnosed with RCC at the age of 11 years.

Conclusion
We suggest a surveillance program for HLRCC including a dermatological examination once every 2 years, annual magnetic resonance imaging starting at the age of 10 years to monitor for early RCCs, annual gynecological examinations from the age of 15 years and counseling regarding risk of hysterectomy and family planning at the age of 18 years. CLMs are often the earliest manifestation of HLRCC, which is why recognizing these lesions, performing a biopsy, and making a prompt referral to genetic counseling is important in order to diagnose HLRCC early.
Eye gaze differences in school scenes between preschool children and adolescents with high-functioning autism spectrum disorder and those with typical development
Authors: Ishizaki Yuko , Higuchi Takahiro , Yanagimoto Yoshitoki , Kobayashi Hodaka , Noritake Atsushi , Nakamura Kae , Kaneko Kazunari 
Published: January 2021

Abstract
Background
Children with autism spectrum disorder (ASD) may experience difficulty adapting to daily life in a preschool or school settings and are likely to develop psychosomatic symptoms. For a better understanding of the difficulties experienced daily by preschool children and adolescents with ASD, this study investigated differences in eye gaze behavior in the classroom environment between children with ASD and those with typical development (TD).

Methods
The study evaluated 30 children with ASD and 49 children with TD. Participants were presented with images of a human face and a classroom scene. While they gazed at specific regions of visual stimuli, eye tracking with an iView X system was used to evaluate and compare the duration of gaze time between the two groups.

Results
Compared with preschool children with TD, preschool children with ASD spent less time gazing at the eyes of the human face and the object at which the teacher pointed in the classroom image. Preschool children with TD who had no classroom experience tended to look at the object the teacher pointed at in the classroom image.

Conclusion
Children with ASD did not look at the human eyes in the facial image or the object pointed at in the classroom image, which may indicate their inability to analyze situations, understand instruction in a classroom, or act appropriately in a group. This suggests that this gaze behavior of children with ASD causes social maladaptation and psychosomatic symptoms. A therapeutic approach that focuses on joint attention is desirable for improving the ability of children with ASD to adapt to their social environment.
Thermal limits for flight activity of field-collected Culicoides in the United Kingdom defined under laboratory conditions
Authors: Tugwell Laura A. , England Marion E. , Gubbins Simon , Sanders Christopher J. , Stokes Jessica E. , Stoner Joanne , Graham Simon P. , Blackwell Alison , Darpel Karin E. , Carpenter Simon 
Published: January 2021

AbstractBackgroundCulicoidesbiting midges (Diptera: Ceratopogonidae) are biological vectors of internationally important arboviruses and inflict biting nuisance on humans, companion animals and livestock. In temperate regions, transmission of arboviruses is limited by temperature thresholds, in both replication and dissemination of arboviruses within the vector and in the flight activity of adultCulicoides. This study aims to determine the cold-temperature thresholds for flight activity ofCulicoidesfrom the UK under laboratory conditions.MethodsOver 18,000Culicoidesadults were collected from the field using 4 W down-draught miniature ultraviolet Centers for Disease Control traps. Populations ofCulicoideswere sampled at three different geographical locations within the UK during the summer months and again in the autumn at one geographical location. Activity at constant temperatures was assessed using a bioassay that detected movement of adultCulicoidestowards an ultraviolet light source over a 24-h period.ResultsThe proportion of active adultCulicoidesincreased with temperature but cold temperature thresholds for activity varied significantly according to collection season and location. Populations dominated by the subgenusAvaritiacollected in South East England had a lower activity threshold temperature in the autumn (4 °C) compared with populations collected in the summer (10 °C). Within the subgenusAvaritia,Culicoides scoticuswas significantly more active across all temperatures tested thanCulicoides obsoletuswithin the experimental setup. Populations ofCulicoides impunctatuscollected in the North East of England were only active once temperatures reached 14 °C. Preliminary data suggested flight activity of the subgenusAvaritiadoes not differ between populations in South East England and those in the Scottish Borders.ConclusionsThese findings demonstrate seasonal changes in temperature thresholds for flight and across different populations ofCulicoides.These data, alongside that defining thresholds for virus replication withinCulicoides,provide a primary tool for risk assessment of arbovirus transmission in temperate regions. In addition, the study also provides a comparison with thermal limits derived directly from light-suction trapping data, which is currently used as the main method to define adultCulicoidesactivity during surveillance.Graphical Abstract