bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ethnozoology among the Berbers: pre-Islamic practices survive in the Rif (northwestern Africa)
Authors: Budjaj Aymane , Benítez Guillermo , Pleguezuelos Juan Manuel 
Published: July 2021

Abstract
Background
Ethnozoological knowledge is less documented than ethnobotanical. With this field study, we aim to record and analyze the Riffian Berber knowledge about the use of animals in traditional human and veterinary medicine. Our research question is what is their knowledge of ethnozoological practices?

Methods
We performed semi-structured interviews with local inhabitants in Riffian vernacular language. The reliability of the sampling effort was assessed by a rarefaction curve. Data were compared with previous studies in order to determine the geographical and historical extensions of described uses and possible conservation implications for the species used.

Results
We obtained information regarding 107 ethnozoological uses based on 197 use reports. Among the 31 species used, mammals were most frequently cited. Diseases related to the traditional medicinal system were most frequently treated with these resources, as well as those of the respiratory, digestive, and musculoskeletal systems. Thirty percent of uses are associated with magico-religious practices. Only three of the species used are threatened at the global level, two of them extinct in the study area, indicating low potential damage to regional biodiversity from current practices utilizing native animals. Within modern Morocco, Riffians have continued practicing ethnozoological uses anathema to Islam, like the consumption of animals considered impure (dogs, jackals, wild boars, and hyenas).

Conclusions
The use of primarily mammalian species and of many animal body parts is likely related to the Berber belief in homology between the area of the human body in which the ailment occurs and the corresponding animal body part. These findings unveil the nature of ethnozoological practices, highly linked to folklore and culture-bound conditions, and lacking in the Western empirical rationale for nearly one third of reported uses. The consumption of animals considered impure according to Islam was probably initiated before the conquering of the Maghreb by Arabs in the seventh century and was maintained through the secular isolation of Riffians in mountain areas. This can reflect traditional healing habits being maintained over thousands of years.
Highly efficient Agrobacterium rhizogenes-mediated hairy root transformation for gene functional and gene editing analysis in soybean
Authors: Cheng Yuanyuan , Wang Xiaoli , Cao Li , Ji Jing , Liu Tengfei , Duan Kaixuan 
Published: July 2021

Abstract
Background
Agrobacterium-mediated genetic transformation is a widely used and efficient technique for gene functional research in crop breeding and plant biology. While in some plant species, including soybean, genetic transformation is still recalcitrant and time-consuming, hampering the high-throughput functional analysis of soybean genes. Thus we pursue to develop a rapid, simple, and highly efficient hairy root system induced by Agrobacterium rhizogenes (A. rhizogenes) to analyze soybean gene function.

Results
In this report, a rapid, simple, and highly efficient hairy root transformation system for soybean was described. Only sixteen days were required for the whole workflow and the system was suitable for various soybean genotypes, with an average transformation frequency of 58–64%. Higher transformation frequency was observed when wounded cotyledons from 1-day-germination seeds were inoculated and co-cultivated with A. rhizogenes in 1/2 B5 (Gamborg’ B-5) medium. The addition of herbicide selection to root production medium increased the transformation frequency to 69%. To test the applicability of the hairy root system for gene functional analysis, we evaluated the protein expression and subcellular localization in transformed hairy roots. Transgenic hairy roots exhibited significantly increased GFP fluorescence and appropriate protein subcellular localization. Protein–protein interactions by BiFC (Bimolecular Fluorescent Complimentary) were also explored using the hairy root system. Fluorescence observations showed that protein interactions could be observed in the root cells. Additionally, hairy root transformation allowed soybean target sgRNA screening for CRISPR/Cas9 gene editing. Therefore, the protocol here enables high-throughput functional characterization of candidate genes in soybean.

Conclusion
A rapid, simple, and highly efficient A. rhizogenes-mediated hairy root transformation system was established for soybean gene functional analysis, including protein expression, subcellular localization, protein–protein interactions and gene editing system evaluation.
Complete response to neoadjuvant chemoradiotherapy in rectal cancer is associated with RAS/AKT mutations and high tumour mutational burden
Authors: Stockton Joanne D. , Tee Louise , Whalley Celina , James Jonathan , Dilworth Mark , Wheat Rachel , Nieto Thomas ,   S-CORT Consortium, Geh Ian , Barros-Silva João D. , Beggs Andrew D. 
Published: July 2021

Abstract
Background
Pathological complete response (pathCR) in rectal cancer is beneficial, as up to 75% of patients do not experience regrowth of the primary tumour, but it is poorly understood. We hypothesised that the changes seen in the pre-treatment biopsies of pathCR but not seen in residual tumour after chemoradiotherapy were the determinants of responsiveness.

Methods
Two groups of patients with either complete response (pathCR group, N = 24) or no response (poor response group, N = 24) were retrieved. Pre-treatment biopsies of cancers from these patients underwent high read depth amplicon sequencing for a targeted panel, exome sequencing, methylation profiling and immunohistochemistry for DNA repair pathway proteins.

Results
Twenty four patients who underwent pathCR and twenty-four who underwent poor response underwent molecular characterisation. Patients in the pathCR group had significantly higher tumour mutational burden and neoantigen load, frequent copy number alterations but fewer structural variants and enrichment for driver mutations in the PI3K/AKT/mTOR signalling pathway. There were no significant differences in tumour heterogeneity as measured by MATH score. Methylation analysis demonstrated enrichment for hypomethyation in the PI3K/AKT/mTOR signalling pathway.

Discussion
The phenomenon of pathCR in rectal cancer may be related to immunovisibility caused by a high tumour mutational burden phenotype. Potential therapy resistance mechanisms involve the PI3K/AKT/mTOR signalling pathway, but tumour heterogeneity does not seem to play a role in resistance.
Clinical, molecular and glycophenotype insights in SLC39A8-CDG
Authors: Bonaventura Eleonora , Barone Rita , Sturiale Luisa , Pasquariello Rosa , Alessandrì Maria Grazia , Pinto Anna Maria , Renieri Alessandra , Panteghini Celeste , Garavaglia Barbara , Cioni Giovanni , Battini Roberta 
Published: July 2021

Abstract
Background
SLC39A8, a gene located on chromosome 4q24, encodes for the manganese (Mn) transporter ZIP8 and its detrimental variants cause a type 2 congenital disorder of glycosylation (CDG). The common SLC39A8 missense variant A391T is associated with increased risk for multiple neurological and systemic disorders and with decreased serum Mn. Patients with SLC39A8-CDG present with different clinical and neuroradiological features linked to variable transferrin glycosylation profile. Galactose and Mn supplementation therapy results in the biochemical and clinical amelioration of treated patients.

Results
Here, we report clinical manifestations, neuroradiological features and glycophenotypes associated with novel SLC39A8 variants (c.1048G > A; p.Gly350Arg and c.131C > G; p.Ser44Trp) in two siblings of the same Italian family. Furthermore, we describe a third patient with overlapping clinical features harbouring the homozygous missense variant A391T. The clinical phenotype of the three patients was characterized by severe developmental disability, dystonic postural pattern and dyskinesia with a more severe progression of the disease in the two affected siblings. Neuroimaging showed a Leigh syndrome-like pattern involving the basal ganglia, thalami and white matter. In the two siblings, atrophic cerebral and cerebellum changes consistent with SLC39A8-CDG were detected as well. Serum transferrin isoelectric focusing (IEF) yielded variable results with slight increase of trisialotransferrin isoforms or even normal pattern. MALDI-MS showed the presence of hypogalactosylated transferrin N-glycans, spontaneously decreasing during the disease course, only in one affected sibling. Total serum N-glycome depicted a distinct pattern for the three patients, with increased levels of undergalactosylated and undersialylated precursors of fully sialylated biantennary glycans, including the monosialo-monogalacto-biantennary species A2G1S1.

Conclusions
Clinical, MRI and glycosylation features of patients are consistent with SLC39A8-CDG. We document two novel variants associated with Leigh syndrome-like disease presentation of SLC39A8-CDG. We show, for the first time, a severe neurological phenotype overlapping with that described for SLC39A8-CDG in association with the homozygous A391T missense variant. We observed a spontaneous amelioration of transferrin N-glycome, highlighting the efficacy of MS-based serum glycomics as auxiliary tool for the diagnosis and clinical management of therapy response in patients with SLC39A8-CDG. Further studies are needed to analyse more in depth the influence of SLC39A8 variants, including the common missense variant, on the expression and function of ZIP8 protein, and their impact on clinical, biochemical and neuroradiological features.
Corticosteroid treatment for acute/acute-on-chronic experimental and naturally occurring pancreatitis in several species: a scoping review to inform possible use in dogs
Authors: Bjørnkjær-Nielsen Kari-Anne , Bjørnvad Charlotte Reinhard 
Published: July 2021

AbstractAcute pancreatitis in dogs is a prevalent disease characterised by mild to severe inflammation. Treatment with anti-inflammatory corticosteroids has been widely debated but is not generally recommended in veterinary medicine. The objective of the present study was to present current evidence on the effect of corticosteroid treatment for acute/acute-on-chronic pancreatitis across species. These findings were then used to evaluate if and how corticosteroid treatment could influence disease outcome in canine acute/acute-on-chronic pancreatitis. A scoping review was performed by searching the Agricola, CAB Abstracts, MEDLINE and Embase databases to identify relevant articles published before June 24, 2021. The inclusion criteria were English language, original research published in a peer-reviewed journal, and investigation of corticosteroid treatment effects on acute/acute-on-chronic pancreatitis by the outcome parameters clinical score, circulating CRP level, hospitalisation duration, mortality and pancreas histopathology. Research on any species was considered. Studies were rated based on the level of evidence, and methodological quality was evaluated based on similarity between groups at baseline, risk of bias and study group size. The reporting method was based on the PRISMA extension for scoping reviews. One thousand nine hundred fifty-four studies were identified, and 31 met the inclusion criteria. Five were canine studies, with 4 investigating experimentally induced pancreatitis; 5 were human clinical studies; and 21 were rodent studies of experimentally induced pancreatitis. The level of evidence ranged between randomised controlled trials and case series, the estimated risk of bias ranged from low to high, and the sample sizes ranged from very small to moderate. Evidence indicates that adding corticosteroid to symptomatic treatment of acute/acute-on-chronic canine pancreatitis could have a positive influence on disease outcome. However, the analysed evidence was based on several species, including both naturally occurring and experimentally induced pancreatitis; thus, the authors suggest that large randomised controlled studies should be performed in dogs with spontaneously occurring acute/acute-on-chronic pancreatitis to further elucidate a potential benefit of corticosteroid treatment.
Successful surgical and medical treatment of a severe, acute epidural bleed in a young dog due to steroid responsive meningitis-arteritis
Authors: Zilli Jessica , Olszewska Agnieszka , Farke Daniela , Schmidt Martin Jürgen 
Published: July 2021

Abstract
Background
Steroid responsive meningitis-arteritis (SRMA) is an immune-mediated disease of the leptomeninges and its associated blood vessels, typically responsive to corticosteroids. Clinically relevant haemorrhage is a rare finding in such patients and for this reason surgical decompression of the spinal cord is normally not considered. The diagnosis of SRMA is supported by serum C-reactive protein (CRP) increase, cerebrospinal fluid (CSF) examination, including cytology (polymorphonuclear pleocytosis in the acute form), nucleated cell-, red blood cell- and protein count, as well as by evaluating CSF and serum IgA concentrations. D-dimer concentrations in serum and CSF should be elevated as well and therefore can be also evaluated as a further diagnostic tool.

Case presentation
A 1.5-year-old mixed breed dog was presented with pyrexia, cervical pain and acute tetraparesis. Magnetic resonance imaging revealed an extradural mass lesion at the level of the sixth cervical vertebra, consistent with a subacute epidural haemorrhage, causing severe compression of the spinal cord. Based on the dog’s signalment, clinical history and results of the blood and CSF analyses (incl. D-dimer determination), SRMA with secondary epidural haemorrhage was suspected. Decompressive surgery was performed through a right sided partial dorsal laminectomy. Post-surgical immunosuppressive treatment was started with cytarabine and then continued with prednisolone after completion of wound healing.

Conclusions
This is the first report in which medical and surgical treatment were combined in a patient with SRMA and it highlights the possibility of performing a successful surgical intervention despite the need for immunosuppressive therapy. Moreover, while SRMA diagnosis is normally based on CSF analysis and CSF and serum IgA concentrations, D-dimer concentrations in serum and CSF were also useful in this patient.
Immuno-genomic classification of colorectal cancer organoids reveals cancer cells with intrinsic immunogenic properties associated with patient survival
Authors: Cho Eun Jeong , Kim Minsuh , Jo Daum , Kim Jihye , Oh Ji-Hye , Chung Hee Chul , Lee Sun-hye , Kim Deokhoon , Chun Sung-Min , Kim Jihun , Lee Hyeonjin , Kim Tae Won , Yu Chang Sik , Sung Chang Ohk , Jang Se Jin 
Published: July 2021

Abstract
Background
The intrinsic immuno-ge7nomic characteristics of colorectal cancer cells that affect tumor biology and shape the tumor immune microenvironment (TIM) are unclear.

Methods
We developed a patient-derived colorectal cancer organoid (CCO) model and performed pairwise analysis of 87 CCOs and their matched primary tumors. The TIM type of the primary tumor was classified as immuno-active, immuno-exhausted, or immuno-desert.

Results
The gene expression profiles, signaling pathways, major oncogenic mutations, and histology of the CCOs recapitulated those of the primary tumors, but not the TIM of primary tumors. Two distinct intrinsic molecular subgroups of highly proliferative and mesenchymal phenotypes with clinical significance were identified in CCOs with various cancer signaling pathways. CCOs showed variable expression of cancer-specific immune-related genes such as those encoding HLA-I and HLA-II, and molecules involved in immune checkpoint activation/inhibition. Among these genes, the expression of HLA-II in CCOs was associated with favorable patient survival. K-means clustering analysis based on HLA-II expression in CCOs revealed a subgroup of patients, in whom cancer cells exhibited Intrinsically Immunogenic Properties (Ca-IIP), and were characterized by high expression of signatures associated with HLA-I, HLA-II, antigen presentation, and immune stimulation. Patients with the Ca-IIP phenotype had an excellent prognosis, irrespective of age, disease stage, intrinsic molecular type, or TIM status. Ca-IIP was negatively correlated with intrinsic E2F/MYC signaling. Analysis of the correlation between CCO immuno-genotype and TIM phenotype revealed that the TIM phenotype was associated with microsatellite instability, Wnt/β-catenin signaling, APC/KRAS mutations, and the unfolded protein response pathway linked to the FBXW7 mutation in cancer cells. However, Ca-IIP was not associated with the TIM phenotype.

Conclusions
We identified a Ca-IIP phenotype from a large set of CCOs. Our findings may provide an unprecedented opportunity to develop new strategies for optimal patient stratification in this era of immunotherapy.
Revealing the full biosphere structure and versatile metabolic functions in the deepest ocean sediment of the Challenger Deep
Authors: Chen Ping , Zhou Hui , Huang Yanyan , Xie Zhe , Zhang Mengjie , Wei Yuli , Li Jia , Ma Yuewei , Luo Min , Ding Wenmian , Cao Junwei , Jiang Tao , Nan Peng , Fang Jiasong , Li Xuan 
Published: July 2021

Abstract
Background
The full biosphere structure and functional exploration of the microbial communities of the Challenger Deep of the Mariana Trench, the deepest known hadal zone on Earth, lag far behind that of other marine realms.

Results
We adopt a deep metagenomics approach to investigate the microbiome in the sediment of Challenger Deep, Mariana Trench. We construct 178 metagenome-assembled genomes (MAGs) representing 26 phyla, 16 of which are reported from hadal sediment for the first time. Based on the MAGs, we find the microbial community functions are marked by enrichment and prevalence of mixotrophy and facultative anaerobic metabolism. The microeukaryotic community is found to be dominated by six fungal groups that are characterized for the first time in hadal sediment to possess the assimilatory and dissimilatory nitrate/sulfate reduction, and hydrogen sulfide oxidation pathways. By metaviromic analysis, we reveal novel hadal Caudovirales clades, distinctive virus-host interactions, and specialized auxiliary metabolic genes for modulating hosts’ nitrogen/sulfur metabolism. The hadal microbiome is further investigated by large-scale cultivation that cataloged 1070 bacterial and 19 fungal isolates from the Challenger Deep sediment, many of which are found to be new species specialized in the hadal habitat.

Conclusion
Our hadal MAGs and isolates increase the diversity of the Challenger Deep sediment microbial genomes and isolates present in the public. The deep metagenomics approach fills the knowledge gaps in structure and diversity of the hadal microbiome, and provides novel insight into the ecology and metabolism of eukaryotic and viral components in the deepest biosphere on earth.
2dFDR: a new approach to confounder adjustment substantially increases detection power in omics association studies
Authors: Yi Sangyoon , Zhang Xianyang , Yang Lu , Huang Jinyan , Liu Yuanhang , Wang Chen , Schaid Daniel J. , Chen Jun 
Published: July 2021

AbstractOne challenge facing omics association studies is the loss of statistical power when adjusting for confounders and multiple testing. The traditional statistical procedure involves fitting a confounder-adjusted regression model for each omics feature, followed by multiple testing correction. Here we show that the traditional procedure is not optimal and present a new approach, 2dFDR, a two-dimensional false discovery rate control procedure, for powerful confounder adjustment in multiple testing. Through extensive evaluation, we demonstrate that 2dFDR is more powerful than the traditional procedure, and in the presence of strong confounding and weak signals, the power improvement could be more than 100%.
Listening to Mom in the NICU: effects of increased maternal speech exposure on language outcomes and white matter development in infants born very preterm
Authors: Brignoni-Pérez Edith , Morales Maya Chan , Marchman Virginia A. , Scala Melissa , Feldman Heidi M. , Yeom Kristen , Travis Katherine E. 
Published: July 2021

Abstract
Background
Infants born very preterm (< 32 weeks gestational age (GA)) are at risk for developmental language delays. Poor language outcomes in children born preterm have been linked to neurobiological factors, including impaired development of the brain’s structural connectivity (white matter), and environmental factors, including decreased exposure to maternal speech in the neonatal intensive care unit (NICU). Interventions that enhance preterm infants’ exposure to maternal speech show promise as potential strategies for improving short-term health outcomes. Intervention studies have yet to establish whether increased exposure to maternal speech in the NICU offers benefits beyond the newborn period for brain and language outcomes.

Methods
This randomized controlled trial assesses the long-term effects of increased maternal speech exposure on structural connectivity at 12 months of age (age adjusted for prematurity (AA)) and language outcomes between 12 and 18 months of age AA. Study participants (N = 42) will include infants born very preterm (24–31 weeks 6/7 days GA). Newborns are randomly assigned to the treatment (n = 21) or standard medical care (n = 21) group. Treatment consists of increased maternal speech exposure, accomplished by playing audio recordings of each baby’s own mother reading a children’s book via an iPod placed in their crib/incubator. Infants in the control group have the identical iPod setup but are not played recordings. The primary outcome will be measures of expressive and receptive language skills, obtained from a parent questionnaire collected at 12–18 months AA. The secondary outcome will be measures of white matter development, including the mean diffusivity and fractional anisotropy derived from diffusion magnetic resonance imaging scans performed at around 36 weeks postmenstrual age during the infants’ routine brain imaging session before hospital discharge and 12 months AA.

Discussion
The proposed study is expected to establish the potential impact of increased maternal speech exposure on long-term language outcomes and white matter development in infants born very preterm. If successful, the findings of this study may help to guide NICU clinical practice for promoting language and brain development. This clinical trial has the potential to advance theoretical understanding of how early language exposure directly changes brain structure for later language learning.

Trial registration
NIH Clinical Trials (ClinicalTrials.gov) NCT04193579. Retrospectively registered on 10 December 2019.