bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the whole standard operating procedure for phage therapy in clinical practice
Authors: Cui Zelin , Guo Xiaokui , Feng Tingting , Li Li 
Published: November 2019

AbstractWe have entered the post-antibiotic era. Phage therapy has recently been given renewed attention because bacteriophages are easily available and can kill bacteria. Many reports have demonstrated successful phage treatment of bacterial infection, whereas some studies have shown that phage therapy is not as effective as expected. In general, establishment of a standard operating procedure will ensure the success of phage therapy. In this paper, the whole operating procedure for phage therapy in clinical practice is explored and analyzed to comprehensively understand the success of using phage for the treatment of bacterial infectious disease in the future. The procedure includes the following: enrollment of patients for phage therapy; establishment of phage libraries; pathogenic bacterial isolation and identification; screening for effective phages against pathogenic bacteria; phage formulation preparation; phage preparation administration strategy and route; monitoring the efficacy of phage therapy; and detection of the emergence of phage-resistant strains. Finally, we outline the whole standard operating procedure for phage therapy in clinical practice. It is believed that phage therapy will be used successfully, especially in personalized medicine for the treatment of bacterial infectious diseases. Hopefully, this procedure will provide support for the entry of phage therapy into the clinic as soon as possible.
Tempol improves neuroinflammation and delays motor dysfunction in a mouse model (SOD1G93A) of ALS
Authors: Chiarotto Gabriela Bortolança , Cartarozzi Luciana Politti , Perez Matheus , Biscola Natalia Perussi , Spejo Aline Barroso , Gubert Fernanda , França Junior Marcondes , Mendez-Otero Rosália , de Oliveira Alexandre Leite Rodrigues 
Published: November 2019

Abstract
Background
The development of new therapeutic strategies to treat amyotrophic lateral sclerosis (ALS) is of utmost importance. The use of cyclic nitroxides such as tempol may provide neuroprotection and improve lifespan. We investigated whether tempol (50 mg/kg) presents therapeutic potential in SOD1G93A transgenic mice.

Methods
Tempol treatment began at the asymptomatic phase of the disease (10th week) and was administered every other day until week 14, after which it was administered twice a week until the final stage of the disease. The animals were sacrificed at week 14 (initial stage of symptoms—ISS) and at the end stage (ES) of the disease. The lumbar spinal cord of the animals was dissected and processed for use in the following techniques: Nissl staining to evaluate neuronal survival; immunohistochemistry to evaluate astrogliosis and microgliosis (ISS and ES); qRT-PCR to evaluate the expression of neurotrophic factors and pro-inflammatory cytokines (ISS); and transmission electron microscopy to evaluate the alpha-motoneurons (ES). Behavioral analyses considering the survival of animals, bodyweight loss, and Rotarod motor performance test started on week 10 and were performed every 3 days until the end-stage of the disease.

Results
The results revealed that treatment with tempol promoted greater neuronal survival (23%) at ISS compared to untreated animals, which was maintained until ES. The intense reactivity of astrocytes and microglia observed in vehicle animals was reduced in the lumbar spinal cords of the animals treated with tempol. In addition, the groups treated with tempol showed reduced expression of proinflammatory cytokines (IL1β and TNFα) and a three-fold decrease in the expression of TGFβ1 at ISS compared with the group treated with vehicle.

Conclusions
Altogether, our results indicate that treatment with tempol has beneficial effects, delaying the onset of the disease by enhancing neuronal survival and decreasing glial cell reactivity during ALS progression in SOD1G93A mice.
Cellular source of hypothalamic macrophage accumulation in diet-induced obesity
Authors: Lee Chan Hee , Shin Sung Hoon , Kang Gil Myoung , Kim Seongjun , Kim Jiye , Yu Rina , Kim Min-Seon 
Published: November 2019

Abstract
Background
Obese mice on a high-fat diet (HFD) display signs of inflammation in the hypothalamic arcuate nucleus (ARC), a critical area for controlling systemic energy metabolism. This has been suggested as a key mechanism of obesity-associated hypothalamic dysfunction. We reported earlier that bone marrow-derived macrophages accumulate in the ARC to sustain hypothalamic inflammation upon chronic exposure to an HFD. However, the mechanism underlying hypothalamic macrophage accumulation has remained unclear.

Methods
We investigated whether circulating monocytes or myeloid precursors contribute to hypothalamic macrophage expansion during chronic HFD feeding. To trace circulating myeloid cells, we generated mice that express green fluorescent protein (GFP) in their lysozyme M-expressing myeloid cells (LysMGFP mice). We conducted parabiosis and bone marrow transplantation experiments using these animals. Mice received an HFD for 12 or 30 weeks and were then sacrificed to analyze LysMGFP cells in the hypothalamus. Hypothalamic vascular permeability in the HFD-fed obese mice was also tested by examining the extravascular leakage of Evans blue and fluorescence-labeled albumin. The timing of LysMGFP cell entry to the hypothalamus during development was also evaluated.

Results
Our parabiosis and bone marrow transplantation experiments revealed a significant infiltration of circulating LysMGFP cells into the liver, skeletal muscle, choroid plexus, and leptomeninges but not in the hypothalamic ARC during chronic HFD feeding, despite increased hypothalamic vascular permeability. These results suggested that the recruitment of circulating monocytes is not a major mechanism for maintaining and expanding the hypothalamic macrophage population in diet-induced obesity. We demonstrated instead that LysMGFP cells infiltrate the hypothalamus during its development. LysMGFP cells appeared in the hypothalamic area from the late embryonic period. This cellular pool suddenly increased immediately after birth, peaked at the postnatal second week, and adopted an adult pattern of distribution after weaning.

Conclusions
Bone marrow-derived macrophages mostly populate the hypothalamus in early postnatal life and may maintain their pool without significant recruitment of circulating monocytes throughout life, even under conditions of chronic HFD feeding.
Codon usage patterns of LT-Ag genes in polyomaviruses from different host species
Authors: Cho Myeongji , Kim Hayeon , Son Hyeon S. 
Published: November 2019

AbstractBackgroundPolyomaviruses (PyVs) have a wide range of hosts, from humans to fish, and their effects on hosts vary. The differences in the infection characteristics of PyV with respect to the host are assumed to be influenced by the biochemical function of the LT-Ag protein, which is related to the cytopathic effect and tumorigenesis mechanism via interaction with the host protein.MethodsWe carried out a comparative analysis of codon usage patterns of large T-antigens (LT-Ags) of PyVs isolated from various host species and their functional domains and sequence motifs. Parity rule 2 (PR2) and neutrality analysis were applied to evaluate the effects of mutation and selection pressure on codon usage bias. To investigate evolutionary relationships among PyVs, we carried out a phylogenetic analysis, and a correspondence analysis of relative synonymous codon usage (RSCU) values was performed.ResultsNucleotide composition analysis usingLT-Aggene sequences showed that the GC and GC3 values of avian PyVs were higher than those of mammalian PyVs. The effective number of codon (ENC) analysis showed host-specific ENC distribution characteristics in both theLT-Aggene and the coding sequences of its domain regions. In the avian and fish PyVs, the codon diversity was significant, whereas the mammalian PyVs tended to exhibit conservative and host-specific evolution of codon usage bias. The results of our PR2 and neutrality analysis revealed mutation bias or highly variable GC contents by showing a narrow GC12 distribution and wide GC3 distribution in all sequences. Furthermore, the calculated RSCU values revealed differences in the codon usage preference of theLT-AGgene according to the host group. A similar tendency was observed in the two functional domains used in the analysis.ConclusionsOur study showed that specific domains or sequence motifs of various PyV LT-Ags have evolved so that each virus protein interacts with host cell targets. They have also adapted to thrive in specific host species and cell types. Functional domains of LT-Ag, which are known to interact with host proteins involved in cell proliferation and gene expression regulation, may provide important information, as they are significantly related to the host specificity of PyVs.
Radiotherapy in metastatic castration resistant prostate cancer patients with oligo-progression during abiraterone-enzalutamide treatment: a mono-institutional experience
Authors: Valeriani Maurizio , Marinelli Luca , Macrini Serena , Reverberi Chiara , Aschelter Anna Maria , De Sanctis Vitaliana , Marchetti Paolo , Tronnolone Lidia , Osti Mattia Falchetto 
Published: November 2019

Abstract
Background
Some patients experience oligo-progression during androgen receptor targeted therapy (ARTT) treatments. This progression might not indicate a real systemic drug resistance, but a selective monoclonal resistance. With the aim to delay the start of new line treatments we treated oligo-progressive sites with radiotherapy.

Methods
From June 2011 to Febrary 2019, 29 consecutive metastatic castration resistant prostate cancer (mCRPC) patients were submitted to radiotherapy for oligo-progression (1–3 sites) during ARTT for a total of 37 lesions treated. Thirty-one (83.8%) lesions were treated with conformal radiotherapy and 6 (16.2%) with stereotactic radiotherapy. After radiotherapy all patients continued ARTT.

Results
Median OS (calculated from ARTT start) was 46,6 months (range 4.4–97.5 months), 2 and 3-year OS were 82.8 and 70.7%, respectively. Median PFS was 18,4 months (range 4.4–45.3 months), 2 and 3-year PFS were 38.3 and 8.5%, respectively. Median overall duration of ARTT treatment was 14.8 months (range 4.4–45.3 months) and median duration of ARTT after radiotherapy was 4.6 months (range 1–33.8 months). Patients submitted to radiotherapy > 6 months from the start of ARTT presented a better PFS (p < 0.001) and a trend toward a better OS (p = 0.101). None patient presented RT and drug related toxicities.

Conclusions
Radiotherapy of oligoprogressive sites may prolong the duration of disease control under ARTT in mCRPC patients with a possible delay in the start of new line treatment. Patients progressing within 6 months from the start of ARTT did not benefit from this approach. More studies are necessary to confirm our results and to evaluate other prognostic factor in order to select patients with high benefit from this approach.
The free neurovascular transverse wrist crease flap for repairing soft tissue defects of the fingers: clinical outcomes of multiple centers
Authors: Fan Zhi-Qiang , Yu Bao-Fu , Zeng Qi , Cai Bo , Xia Guo-Ming , Huang Sheng-Hui 
Published: November 2019

Abstract
Background
Flap transplantation is often needed for soft tissue defects of the fingers that cannot be closed directly. Sensory reconstruction of the fingers is important for patients to recover feelings. In this study, we report clinical outcomes of using free neurovascular transverse wrist crease flap for repairing finger defects from multiple centers.

Methods
This case series includes 72 consecutive patients with finger defects between June 2013 and June 2016 from multiple centers. A neurovascular transverse free radial artery superficial palmar branch flap, named transverse wrist crease flap, was designed to reconstruct soft tissue defects of the fingers with microvascular anastomosis. When there were soft tissue defects of the fingers with digital nerve defect, end-to-end neurorrhaphy between the median palmar cutaneous branch and the digital nerves was also performed. The donor incision was sutured directly. All the patients were followed-up for more than 24 months.

Results
The soft tissue defects of the fingers were all completely covered with this free neurovascular transverse wrist crease flap, and the flaps in 71 patients survived completely without ischemia. Vascular crisis appeared in one case, and the wound healed gradually after changing wound dressing for nearly 1 month. Slight infections of wounds appeared in eight cases. There were no complications in the donor site, like infection and poor wound healing. At the last follow-up, the mean static two-point discrimination was 9.6 ± 2.4 mm on the injured finger and 4.5 ± 0.8 on the contralateral corresponding finger. The motion range of the distal interphalangeal joint and proximal interphalangeal joint on the injured finger were 72.5 ± 23.3% and 78.7 ± 32.5% of the contralateral corresponding finger, respectively. Patient self-evaluations were good in 53 cases and fair in 19 cases.

Conclusions
The results indicate that the free neurovascular transverse wrist crease flap is a good choice for repairing soft tissue defects of the fingers.

Level of evidence
Therapeutic IV
Kabuki syndrome: novel pathogenic variants, new phenotypes and review of literature
Authors: Shangguan Huakun , Su Chang , Ouyang Qian , Cao Bingyan , Wang Jian , Gong Chunxiu , Chen Ruimin 
Published: November 2019

Abstract
Objective
This study describes 5 novel variants of 7 KMT2D/KDM6A gene and summarizes the clinical manifestations and the mutational spectrum of 47 Chinese Kabuki syndrome (KS) patients.

Methods
Blood samples were collected for whole-exome sequencing (WES) for 7 patients and their parents if available. Phenotypic and genotypic spectra of 40 previously published unrelated Chinese KS patients were summarized.

Result
Genetic sequencing identified six KMT2D variants (c.3926delC, c.5845delC, c.6595delT, c.12630delG, c.16294C > T, and c.16442delG) and one KDM6A variant (c.2668-2671del). Of them, 4 variants (c.3926delC, c.5845delC, c.12630delG, and c.16442delG) in KMT2D gene and the variant (c.2668-2671del) in KDM6A gene were novel. Combining with previously published Chinese KS cases, the patients presented with five cardinal manifestations including facial dysmorphism, intellectual disability, growth retardation, fingertip pads and skeletal abnormalities. In addition, 29.5% (5/17) patients had brain abnormalities, such as hydrocephalus, cerebellar vermis dysplasia, thin pituitary and white matter myelination delay, corpus callosum hypoplasia and Dandy-Walker malformation.

Conclusion
In this report, five novel variants in KMT2D/KDM6A genes are described. A subset of Chinese KS patients presented with brain abnormalities that were not previously reported. Our study expands the mutational and phenotypic spectra of KS.
A comprehensive monocentric ophthalmic study with Gaucher disease type 3 patients: vitreoretinal lesions, retinal atrophy and characterization of abnormal saccades
Authors: Hopf Susanne , Pfeiffer Norbert , Liesenfeld Matthias , Mengel Karl-Eugen , Hennermann Julia B. , Schmidtmann Irene , Pitz Susanne 
Published: November 2019

Summary
Background
The differentiation between Gaucher disease type 3 (GD3) and type 1 is challenging because pathognomonic neurologic symptoms may be subtle and develop at late stages. The ophthalmologist plays a crucial role in identifying the typical impairment of horizontal saccadic eye movements, followed by vertical ones. Little is known about further ocular involvement. The aim of this monocentric cohort study is to comprehensively describe the ophthalmological features of Gaucher disease type 3. We suggest recommendations for a set of useful ophthalmologic investigations for diagnosis and follow up and for saccadometry parameters enabling a correlation to disease severity.

Methods
Sixteen patients with biochemically and genetically diagnosed GD3 completed ophthalmologic examination including optical coherence tomography (OCT), clinical oculomotor assessment and saccadometry by infrared based video-oculography. Saccadic peak velocity, gain and latency were compared to 100 healthy controls, using parametric tests. Correlations between saccadic assessment and clinical parameters were calculated.

Results
Peripapillary subretinal drusen-like deposits with retinal atrophy (2/16), preretinal opacities of the vitreous (4/16) and increased retinal vessel tortuosity (3/16) were found. Oculomotor pathology with clinically slowed saccades was more frequent horizontally (15/16) than vertically (12/16). Saccadometry revealed slowed peak velocity compared to 100 controls (most evident horizontally and downwards). Saccades were delayed and hypometric. Best correlating with SARA (scale for the assessment and rating of ataxia), disease duration, mSST (modified Severity Scoring Tool) and reduced IQ was peak velocity (both up- and downwards). Motility restriction occurred in 8/16 patients affecting horizontal eye movements, while vertical motility restriction was seen less frequently. Impaired abduction presented with esophoria or esotropia, the latter in combination with reduced stereopsis.

Conclusions
Vitreoretinal lesions may occur in 25% of Gaucher type 3 patients, while we additionally observed subretinal lesions with retinal atrophy in advanced disease stages. Vertical saccadic peak velocity seems the most promising “biomarker” for neuropathic manifestation for future longitudinal studies, as it correlates best with other neurologic symptoms. Apart from the well documented abduction deficit in Gaucher type 3 we were able to demonstrate motility impairment in all directions of gaze.
OrthoFinder: phylogenetic orthology inference for comparative genomics
Authors: Emms David M. , Kelly Steven 
Published: November 2019

AbstractHere, we present a major advance of the OrthoFinder method. This extends OrthoFinder’s high accuracy orthogroup inference to provide phylogenetic inference of orthologs, rooted gene trees, gene duplication events, the rooted species tree, and comparative genomics statistics. Each output is benchmarked on appropriate real or simulated datasets, and where comparable methods exist, OrthoFinder is equivalent to or outperforms these methods. Furthermore, OrthoFinder is the most accurate ortholog inference method on the Quest for Orthologs benchmark test. Finally, OrthoFinder’s comprehensive phylogenetic analysis is achieved with equivalent speed and scalability to the fastest, score-based heuristic methods. OrthoFinder is available at https://github.com/davidemms/OrthoFinder.
mPies: a novel metaproteomics tool for the creation of relevant protein databases and automatized protein annotation
Authors: Werner Johannes , Géron Augustin , Kerssemakers Jules , Matallana-Surget Sabine 
Published: November 2019

Abstract
Metaproteomics allows to decipher the structure and functionality of microbial communities. Despite its rapid development, crucial steps such as the creation of standardized protein search databases and reliable protein annotation remain challenging. To overcome those critical steps, we developed a new program named mPies (metaProteomics in environmental sciences). mPies allows the creation of protein databases derived from assembled or unassembled metagenomes, and/or public repositories based on taxon IDs, gene or protein names. For the first time, mPies facilitates the automatization of reliable taxonomic and functional consensus annotations at the protein group level, minimizing the well-known protein inference issue, which is commonly encountered in metaproteomics. mPies’ workflow is highly customizable with regards to input data, workflow steps, and parameter adjustment. mPies is implemented in Python 3/Snakemake and freely available on GitHub: https://github.com/johanneswerner/mPies/.

Reviewer
This article was reviewed by Dr. Wilson Wen Bin Goh.
Using imperfect data in predictive mapping of vectors: a regional example of Ixodes ricinus distribution
Authors: Ribeiro Rita , Eze Jude I. , Gilbert Lucy , Wint G. R. William , Gunn George , Macrae Alastair , Medlock Jolyon M. , Auty Harriet 
Published: November 2019

Abstract
Background
Knowledge of Ixodes ricinus tick distribution is critical for surveillance and risk management of transmissible tick-borne diseases such as Lyme borreliosis. However, as the ecology of I. ricinus is complex, and robust long-term geographically extensive distribution tick data are limited, mapping often relies on datasets collected for other purposes. We compared the modelled distributions derived from three datasets with information on I. ricinus distribution (quantitative I. ricinus count data from scientific surveys; I. ricinus presence-only data from public submissions; and a combined I. ricinus dataset from multiple sources) to assess which could be reliably used to inform Public Health strategy. The outputs also illustrate the strengths and limitations of these three types of data, which are commonly used in mapping tick distributions.

Methods
Using the Integrated Nested Laplace algorithm we predicted I. ricinus abundance and presence–absence in Scotland and tested the robustness of the predictions, accounting for errors and uncertainty.

Results
All models fitted the data well and the covariate predictors for I. ricinus distribution, i.e. deer presence, temperature, habitat, index of vegetation, were as expected. Differences in the spatial trend of I. ricinus distribution were evident between the three predictive maps. Uncertainties in the spatial models resulted from inherent characteristics of the datasets, particularly the number of data points, and coverage over the covariate range used in making the predictions.

Conclusions
Quantitative I. ricinus data from scientific surveys are usually considered to be gold standard data and we recommend their use where high data coverage can be achieved. However in this study their value was limited by poor data coverage. Combined datasets with I. ricinus distribution data from multiple sources are valuable in addressing issues of low coverage and this dataset produced the most appropriate map for national scale decision-making in Scotland. When mapping vector distributions for public-health decision making, model uncertainties and limitations of extrapolation need to be considered; these are often not included in published vector distribution maps. Further development of tools to better assess uncertainties in the models and predictions are necessary to allow more informed interpretation of distribution maps.
Global stability of an SEIR epidemic model where empirical distribution of incubation period is approximated by Coxian distribution
Authors: Kim Sungchan , Byun Jong Hyuk , Jung Il Hyo 
Published: November 2019

AbstractIn this work, we have developed a Coxian-distributed SEIR model when incorporating an empirical incubation period. We show that the global dynamics are completely determined by a basic reproduction number. An application of the Coxian-distributed SEIR model using data of an empirical incubation period is explored. The model may be useful for resolving the realistic intrinsic parts in classical epidemic models since Coxian distribution approximately converges to any distribution.