bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pedigree and genome-based patterns of homozygosity in the South African Ayrshire, Holstein, and Jersey breeds
Authors: Visser Carina , Lashmar Simon Frederick , Reding Jason , Berry Donagh P. , van Marle-Köster Esté 
Published: March 2023

The erosion of genetic diversity limits long-term genetic gain and impedes the sustainability of livestock production. In the South African (SA) dairy industry, the major commercial dairy breeds have been applying estimated breeding values (EBVs) and/or have been participating in Multiple Across Country Evaluations (MACE). The transition to genomic estimated breeding values (GEBVs) in selection strategies requires monitoring of the genetic diversity and inbreeding of current genotyped animals, especially considering the comparatively small population sizes of global dairy breeds in SA. This study aimed to perform a homozygosity-based evaluation of the SA Ayrshire (AYR), Holstein (HST), and Jersey (JER) dairy cattle breeds. Three sources of information, namely 1) single nucleotide polymorphism (SNP) genotypes (3,199 animals genotyped for 35,572 SNPs) 2) pedigree records (7,885 AYR; 28,391 HST; 18,755 JER), and 3) identified runs of homozygosity (ROH) segments were used to quantify inbreeding related parameters. The lowest pedigree completeness was for the HST population reducing from a value of 0.990 to 0.186 for generation depths of one to six. Across all breeds, 46.7% of the detected ROH were between 4 megabase pairs (Mb) and 8 Mb in length. Two conserved homozygous haplotypes were identified in more than 70% of the JER population onBos taurusautosome (BTA) 7. The JER breed displayed the highest level of inbreeding across all inbreeding coefficients. The mean (± standard deviation) pedigree-based inbreeding coefficient (FPED) ranged from 0.051 (±0.020) for AYR to 0.062 (±0.027) for JER, whereas SNP-based inbreeding coefficients (FSNP) ranged from 0.020 (HST) to 0.190 (JER) and ROH-based inbreeding coefficients, considering all ROH segment coverage (FROH), ranged from 0.053 (AYR) to 0.085 (JER). Within-breed Spearman correlations between pedigree-based and genome-based estimates ranged from weak (AYR: 0.132 between FPED and FROHcalculated for ROH &lt;4Mb in size) to moderate (HST: 0.584 between FPEDand FSNP). Correlations strengthened between FPEDand FROHas the ROH length category was considered lengthened, suggesting a dependency on breed-specific pedigree depth. The genomic homozygosity-based parameters studied proved useful in investigating the current inbreeding status of reference populations genotyped to implement genomic selection in the three most prominent South African dairy cattle breeds.
Identification of immune related molecular subtypes and prognosis model for predicting prognosis, drug resistance in cervical squamous cell carcinoma
Authors: Hu Dongzhi , Zhang Zijian , Zhang Yongjing , Huang Kangni , Li Xiaoxue 
Published: March 2023

Background: One of the features of tumor immunity is the immunosuppressive tumor microenvironment (TME). In this study, TME gene signatures were used to define the characteristics of Cervical squamous cell carcinoma (CESC) immune subtypes and construct a new prognostic model.Methods: Single sample gene set enrichment analysis (ssGSEA) was used to quantify pathway activity. RNA-seq of 291 CESC were obtained from the Cancer Genome Atlas (TCGA) database as a training set. Microarray-based data of 400 cases of CESC were obtained from the Gene Expression Compilation (GEO) database as an independent validation set. 29 TME related gene signatures were consulted from previous study. Consensus Cluster Plus was employed to identify molecular subtype. Univariate cox regression analysis and random survival forest (RSF) were used to establish the immune-related gene risk model based on the TCGA data set of CESC, and the accuracy of prognosis prediction was verified by GEO data set. ESTIMATE algorithm was used to perform immune and matrix scores on the data set.Results: three molecular subtypes (C1, C2, C3) were screened in TCGA-CESC on account of 29 TME gene signatures. Among, C3 with better survival outcome had higher immune related gene signatures, while C1 with worse prognosis time had enhanced matrix related features. Increased immune infiltration, inhibition of tumor related pathways, widespread genomic mutations and prone immunotherapy were observed in C3. Furthermore, a five immune genes signature was constructed and predicted overall survival for CESC, which successfully validated in GSE44001 dataset. A positive phenomenon was observed between five hub genes expressions and methylation. Similarly, high group enriched in matrix related features, while immune related gene signatures were enriched in low group. Immune cell, immune checkpoints genes expression levels were negatively, while most TME gene signatures were positively correlated with Risk Score. In addition, high group was more sensitive to drug resistance.Conclusion: This work identified three distinct immune subtypes and a five genes signature for predicting prognosis in CESC patients, which provided a promising treatment strategy for CESC.
Three distinct mechanisms underlying human γδ T cell-mediated cytotoxicity against malignant pleural mesothelioma
Authors: Umeyama Yasuhiro , Taniguchi Hirokazu , Gyotoku Hiroshi , Senju Hiroaki , Tomono Hiromi , Takemoto Shinnosuke , Yamaguchi Hiroyuki , Tagod Mohammed S. O. , Iwasaki Masashi , Tanaka Yoshimasa , Mukae Hiroshi 
Published: March 2023

IntroductionMalignant pleural mesothelioma (MPM) is a rare and highly aggressive thoracic tumor with poor prognosis and limited therapeutic options. Although immune checkpoint inhibitors exhibit a promising effect in some patients with unresectable MPM in clinical trials, the majority of MPM patients show only modest response rates to the currently available treatments. It is thus imperative to develop novel and innovative therapeutic modalities for MPM, including immune effector cell-based therapies.Methodsγδ T cells were expanded using tetrakis-pivaloyloxymethyl 2-(thiazole-2-ylamino) ethylidene-1,1-bisphosphonate (PTA) and interleukin-2, and the therapeutic potential of γδ T cells was examined through analyzing cell surface markers and cellular cytotoxicity against MPM in vitro using a europium chelate-based time-resolved fluorescence assay system and a luciferase-based luminescence assay system.Results and discussionWe successfully expanded γδ T cells from peripheral blood mononuclear cells of healthy donors and MPM patients. γδ T cells expressed natural killer receptors such as NKG2D and DNAM-1 and exhibited a moderate level of cytotoxicity to MPM cells in the absence of antigens. The inclusion of PTA, (E)-4-hydroxy-3- methylbut-2-enyl diphosphate (HMBPP) or zoledronic acid (ZOL) induced a TCR-dependent cytotoxicity in γδ T cells and secreted interferon-γ (IFN-γ). In addition, γδ T cells expressing CD16 exhibited a significant level of cytotoxicity against MPM cells in the presence of an anti-epidermal growth factor receptor (EGFR) mAb, at lower concentrations than in clinical settings, whereas a detectable level of IFN-γ was not produced. Taken together, γδ T cells showed cytotoxic activity against MPM in three distinct mechanisms through NK receptors, TCRs and CD16. Since major histocompatibility complex (MHC) molecules are not involved in the recognition, both autologous and allogeneic γδ T cells could be used for the development of γδ T cell-based adoptive immunotherapy for MPM.
BTG2 and SerpinB5, a novel gene pair to evaluate the prognosis of lung adenocarcinoma
Authors: Yang Wanting , Wei Chunli , Cheng Jingliang , Ding Ran , Li Yan , Wang Yonghua , Yang Yinfeng , Wang Jinghui 
Published: March 2023

IntroductionLung adenocarcinoma (LUAD), as the most frequent pathological subtype of non−small cell lung cancer, is often characterized by poor prognosis and low 5-year survival rate. Exploriton of new biomarkers and accurate molecular mechanisms for effectively predicting the prognosis of LUAD patients is still necessary. Presently, BTG2 and SerpinB5, which play important roles in tumors, are studied as a gene pair for the first time with the aim of exploring whether they can be used as potential prognostic markers.MethodsUsing the bioinformatics method to explore whether BTG2 and SerpinB5 can become independent prognostic factors, and explore their clinical application value and whether they can be used as immunotherapeutic markers. In addition, we also verify the conclusions obtained from external datasets, molecular docking, and SqRT-PCR.ResultsThe results show that compared with normal lung tissue, BTG2 expression level was down-regulated and SerpinB5 was up-regulated in LUAD. Additionally, Kaplan–Meier survival analysis demonstrate that the prognosis of low expression level of BTG2 was poor, and that of high expression level of SerpinB5 was poor, suggesting that both of them can be used as independent prognostic factors. Moreover, the prognosis models of the two genes were constructed respectively in this study, and their prediction effect was verified by external data. Besides, ESTIMATE algorithm reveals the relationship between this gene pair and the immune microenvironment. Furthermore, patients with a high expression level of BTG2 and a low expression level of SerpinB5 have higher immunophenoscore for CTLA-4 and PD-1 inhibitors than patients with a low expression level of BTG2 and a high expression level of SerpinB5, indicating that such patients have a more obvious effect of immunotherapy.DiscussionCollectively, all the results demonstrate that BTG2 and SerpinB5 might serve as potential prognostic biomarkers and novel therapeutic targets for LUAD.
Ecological carrying capacity and carbon sequestration potential of bivalve shellfish in marine ranching: A case study in Bohai Bay, China
Authors: Li Zepeng , Chen Yan , Wang Gang , Mu Jiandong , Sun Yanfeng , Yu Haolin , Xu Jiangling , Yan Ying , Luo Shuangyue , Han Fuqiang , Feng Jie , Pan Zhe 
Published: March 2023

IntroductionShellfish play an important role in ecological restoration and as carbon (C) sinks, but studies on their ecological carrying capacity (ECC) and C sequestration potential are sparse.MethodsIn this study, we selected a 57-hectare artificial oyster reef in a typical marine ranching in Bohai Bay, China, to evaluate the ECC and their C sequestration potential of bivalve shellfish, and projecting their impact on functional groups in the system, with an Ecopath with Ecosim (EwE) food web model. We conducted four biological surveys to obtain the biomass measurements, with one conducted in each of the summer, autumn, and winter of 2019 and one in the spring of 2020; and the functional groups included in the surveys comprised fish, cephalopods, crustaceans, snails, bivalve shellfish, annelids, other macrobenthos, meiobenthos, starfish, sea cucumbers, zooplankton, phytoplankton, and detritus.Results and DiscussionThe EwE model prediction results showed that the ECC of bivalve shellfish was established to be 282.66 t/km2, far more than the existing quantity of 187.76 t/km2. Therefore, at present, the ecosystem of the study marine ranching is not yet mature. Moreover, our ecological network analysis parameters indicated that the marine ranching ecosystem will be mature and stable when the bivalve shellfish population reaches its ECC. However, the increase in bivalve shellfish biomass will result in a decrease in the population sizes of species competing for food resources with bivalve shellfish, mainly gobiid fish such as Tridentiger bifasciatus, Tridentiger trigonocephalus, Tridentiger barbatus. Simultaneously, when the bivalve shellfish reach their ECC, 29.23 t of CO2 can be sequestrated by bivalve shellfish, comprising 14.32 t being removed from the ecosystem as prey and 14.91 t being stored on the seafloor through biodeposition.ConclusionTherefore, the research demonstrated that, within the scope of ECC, the increasing bivalve shellfish can improve the C sequestration capacity of the marine ranch ecosystem, and effective management of bivalve shellfish in marine ranching can improve the economic benefits and C sink service functions of marine ranching.
D-dimer trends elaborate the heterogeneity of risk in hospitalized patients with COVID-19: A multi-national case series from different waves
Authors: Ronderos Botero Diana Maria , Omar Alaa Mabrouk Salem , Pengo Martino F. , Haider Syed Waqas , Latif Hira , Parati Gianfranco , Pengo Vittorio , Cañas Arboleda Alejandra , Díaz Melissa , Villaquirán-Torres Claudio , Contreras Johanna , Chilimuri Sridhar 
Published: March 2023

IntroductionVariable D-dimer trends during hospitalization reportedly result in distinct in-hospital mortality. In this multinational case series from the first and second waves, we show the universality of such D-dimer trends.MethodsWe reviewed 405 patients with COVID-19 during the first wave admitted to three institutions in the United States, Italy, and Colombia, and 111 patients admitted to the U.S. site during the second wave and 55 patients during the third wave. D-dimer was serially followed during hospitalization.ResultsDuring the first wave, 66 (15%) patients had a persistently-low pattern, 33 (8%) had early-peaking, 70 (16%) had mid-peaking, 94 (22%) had fluctuating, 30 (7%) had late-peaking, and 112 (26%) had a persistently-high pattern. During the second and third waves, similar patterns were observed. D-dimer patterns were significantly different in terms of in-hospital mortality similarly in all waves. Patterns were then classified into low-risk patterns (persistently-low and early-peaking), where no deaths were observed in both waves, high-risk patterns (mid-peaking and fluctuating), and malignant patterns (late-peaking and persistently-high). Overall, D-dimer trends were associated with an increased risk for in-hospital mortality in the first wave (overall: HR: 1.73) and stayed the same during the second (HR: 1.67, p &lt; 0.001) and the third (HR: 4.4, p = 0.001) waves.ConclusionD-dimer behavior during COVID-19 hospitalization yielded universal categories with distinct mortality risks that persisted throughout all studied waves of infection. Monitoring D-dimer behavior may be useful in the management of these patients.
3D electron microscopy and volume-based bouton sorting reveal the selectivity of inputs onto geniculate relay cell and interneuron dendrite segments
Authors: Maher Erin E. , Briegel Alex C. , Imtiaz Shahrozia , Fox Michael A. , Golino Hudson , Erisir Alev 
Published: March 2023

IntroductionThe visual signals evoked at the retinal ganglion cells are modified and modulated by various synaptic inputs that impinge on lateral geniculate nucleus cells before they are sent to the cortex. The selectivity of geniculate inputs for clustering or forming microcircuits on discrete dendritic segments of geniculate cell types may provide the structural basis for network properties of the geniculate circuitry and differential signal processing through the parallel pathways of vision. In our study, we aimed to reveal the patterns of input selectivity on morphologically discernable relay cell types and interneurons in the mouse lateral geniculate nucleus.MethodsWe used two sets of Scanning Blockface Electron Microscopy (SBEM) image stacks and Reconstruct software to manually reconstruct of terminal boutons and dendrite segments. First, using an unbiased terminal sampling (UTS) approach and statistical modeling, we identified the criteria for volume-based sorting of geniculate boutons into their putative origins. Geniculate terminal boutons that were sorted in retinal and non-retinal categories based on previously described mitochondrial morphology, could further be sorted into multiple subpopulations based on their bouton volume distributions. Terminals deemed non-retinal based on the morphological criteria consisted of five distinct subpopulations, including small-sized putative corticothalamic and cholinergic boutons, two medium-sized putative GABAergic inputs, and a large-sized bouton type that contains dark mitochondria. Retinal terminals also consisted of four distinct subpopulations. The cutoff criteria for these subpopulations were then applied to datasets of terminals that synapse on reconstructed dendrite segments of relay cells or interneurons.ResultsUsing a network analysis approach, we found an almost complete segregation of retinal and cortical terminals on putative X-type cell dendrite segments characterized by grape-like appendages and triads. On these cells, interneuron appendages intermingle with retinal and other medium size terminals to form triads within glomeruli. In contrast, a second, presumed Y-type cell displayed dendrodendritic puncta adherentia and received all terminal types without a selectivity for synapse location; these were not engaged in triads. Furthermore, the contribution of retinal and cortical synapses received by X-, Y- and interneuron dendrites differed such that over 60% of inputs to interneuron dendrites were from the retina, as opposed to 20% and 7% to X- and Y-type cells, respectively.ConclusionThe results underlie differences in network properties of synaptic inputs from distinct origins on geniculate cell types.
A risk-predictive model for obstructive sleep apnea in patients with chronic obstructive pulmonary disease
Authors: Peng Tianfeng , Yuan Shan , Wang Wenjing , Li Zhuanyun , Jumbe Ayshat Mussa , Yu Yaling , Hu Zhenghao , Niu Ruijie , Wang Xiaorong , Zhang Jinnong 
Published: March 2023

BackgroundObstructive sleep apnea syndrome (OSA) is increasingly reported in patients with chronic obstructive pulmonary disease (COPD). Our research aimed to analyze the clinical characteristics of patients with overlap syndrome (OS) and develop a nomogram for predicting OSA in patients with COPD.MethodsWe retroactively collected data on 330 patients with COPD treated at Wuhan Union Hospital (Wuhan, China) from March 2017 to March 2022. Multivariate logistic regression was used to select predictors applied to develop a simple nomogram. The area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA) were used to assess the value of the model.ResultsA total of 330 consecutive patients with COPD were enrolled in this study, with 96 patients (29.1%) confirmed with OSA. Patients were randomly divided into the training group (70%, n = 230) and the validation group (30%, n = 100). Age [odds ratio (OR): 1.062, 1.003–1.124], type 2 diabetes (OR: 3.166, 1.263–7.939), neck circumference (NC) (OR: 1.370, 1.098–1,709), modified Medical Research Council (mMRC) dyspnea scale (OR: 0.503, 0.325–0.777), Sleep Apnea Clinical Score (SACS) (OR: 1.083, 1.004–1.168), and C-reactive protein (CRP) (OR: 0.977, 0.962–0.993) were identified as valuable predictors used for developing a nomogram. The prediction model performed good discrimination [AUC: 0.928, 95% confidence interval (CI): 0.873–0.984] and calibration in the validation group. The DCA showed excellent clinical practicability.ConclusionWe established a concise and practical nomogram that will benefit the advanced diagnosis of OSA in patients with COPD.
CLL stereotyped B-cell receptor immunoglobulin sequences are recurrent in the B-cell repertoire of healthy individuals: Apparent lack of central and early peripheral tolerance censoring
Authors: Vergani Stefano , Bagnara Davide , Agathangelidis Andreas , Ng Anita Kar Yun , Ferrer Gerardo , Mazzarello Andrea N. , Palacios Florencia , Yancopoulos Sophia , Yan Xiao-Jie , Barrientos Jaqueline C. , Rai Kanti R. , Stamatopoulos Kostas , Chiorazzi Nicholas 
Published: March 2023

IntroductionThe leukemic cells of patients with chronic lymphocytic leukemia (CLL) are often unique, expressing remarkably similar IGHV-IGHD-IGHJ gene rearrangements, “stereotyped BCRs”. The B-cell receptors (BCRs) on CLL cells are also distinctive in often deriving from autoreactive B lymphocytes, leading to the assumption of a defect in immune tolerance.ResultsUsing bulk and single-cell immunoglobulin heavy and light chain variable domain sequencing, we enumerated CLL stereotype-like IGHV-IGHD-IGHJ sequences (CLL-SLS) in B cells from cord blood (CB) and adult peripheral blood (PBMC) and bone marrow (BM of healthy donors. CLL-SLS were found at similar frequencies among CB, BM, and PBMC, suggesting that age does not influence CLL-SLS levels. Moreover, the frequencies of CLL-SLS did not differ among B lymphocytes in the BM at early stages of development, and only re-circulating marginal zone B cells contained significantly higher CLL-SLS frequencies than other mature B-cell subpopulations. Although we identified CLL-SLS corresponding to most of the CLL major stereotyped subsets, CLL-SLS frequencies did not correlate with those found in patients. Interestingly, in CB samples, half of the CLL-SLS identified were attributed to two IGHV-mutated subsets. We also found satellite CLL-SLS among the same normal samples, and they were also enriched in naïve B cells but unexpectedly, these were ~10-fold higher than standard CLL-SLS. In general, IGHV-mutated CLL-SLS subsets were enriched among antigen-experienced B-cell subpopulations, and IGHV-unmutated CLL-SLS were found mostly in antigen-inexperienced B cells. Nevertheless, CLL-SLS with an IGHV-mutation status matching that of CLL clones varied among the normal B-cell subpopulations, suggesting that specific CLL-SLS could originate from distinct subpopulations of normal B cells. Lastly, using single-cell DNA sequencing, we identified paired IGH and IGL rearrangements in normal B lymphocytes resembling those of stereotyped BCRs in CLL, although some differed from those in patients based on IG isotype or somatic mutation.DiscussionCLL-SLS are present in normal B-lymphocyte populations at all stages of development. Thus, despite their autoreactive profile they are not deleted by central tolerance mechanisms, possibly because the level of autoreactivity is not registered as dangerous by deletion mechanisms or because editing of L-chain variable genes occurred which our experimental approach could not identify.
Long-term outcome after combined or sequential liver and kidney transplantation in children with infantile and juvenile primary hyperoxaluria type 1
Authors: Loos Sebastian , Kemper Markus J. , Schmaeschke Kaja , Herden Uta , Fischer Lutz , Hoppe Bernd , Levart Tanja Kersnik , Grabhorn Enke , Schild Raphael , Oh Jun , Brinkert Florian 
Published: March 2023

IntroductionCombined or sequential liver and kidney transplantation (CLKT/SLKT) restores kidney function and corrects the underlying metabolic defect in children with end-stage kidney disease in primary hyperoxaluria type 1 (PH1). However, data on long-term outcome, especially in children with infantile PH1, are rare.MethodsAll pediatric PH1-patients who underwent CLKT/SLKT at our center were analyzed retrospectively.ResultsEighteen patients (infantile PH1 n = 10, juvenile PH1 n = 8) underwent transplantation (CLKT n = 17, SLKT n = 1) at a median age of 5.4 years (1.5–11.8). Patient survival was 94% after a median follow-up of 9.2 years (6.4–11.0). Liver and kidney survival-rates after 1, 10, and 15 years were 90%, 85%, 85%, and 90%, 75%, 75%, respectively. Age at transplantation was significantly lower in infantile than juvenile PH1 (1.6 years (1.4–2.4) vs. 12.8 years (8.4–14.1), P = 0.003). Median follow-up was 11.0 years (6.8–11.6) in patients with infantile PH1 vs. 6.9 years (5.7–9.9) in juvenile PH1 (P = 0.15). At latest follow-up kidney and/or liver graft loss and/or death showed a tendency to a higher rate in patients with infantile vs. juvenile PH1 (3/10 vs. 1/8, P = 0.59).DiscussionIn conclusion, the overall patient survival and long-term transplant outcome of patients after CLKT/SLKT for PH1 is encouraging. However, results in infantile PH1 tended to be less optimal than in patients with juvenile PH1.