bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mismatch in SIRPα, a regulatory protein in innate immunity, is associated with chronic GVHD in hematopoietic stem cell transplantation
Authors: Saliba Rima M. , Greenbaum Uri , Ma Qing , Srour Samer A. , Carmazzi Yudith , Li Liang , Oran Betul , Moller Michael , Wood Janet , Ciurea Stefan O. , Kongtim Piyanuch , Rondon Gabriela , Partlow David , Li Dan , Rezvani Katayoun , Shpall Elizabeth J. , Cao Kai , Champlin Richard E. , Zou Jun 
Published: September 2021

Abstract
Recent compelling evidence showed that innate immune effector cells could recognize allogeneic grafts and prime an adaptive immune response. Signal regulatory protein α (SIRPα) is an immunoglobulin superfamily receptor that is expressed on myeloid cells; the interaction between SIRPα and its ubiquitously expressed ligand CD47 elicits an inhibitory signal that suppresses macrophage phagocytic function. Additional studies showed that donor-recipient mismatch in SIRPα variants might activate monocytic allorecognition, possibly as the result of non-self SIRPα-CD47 interaction. However, the frequency of SIRPα variation and its role in hematopoietic stem cell transplantation (HSCT) remains unexplored. We studied 350 patients with acute myeloid leukemia/myelodysplastic syndrome who underwent HLA-matched related HSCT and found that SIRPα allelic mismatches were present in 39% of transplantation pairs. SIRPα variant mismatch was associated with a significantly higher rate of chronic graft-versus-host disease (GVHD; hazard ratio [HR], 1.5; P = .03), especially de novo chronic GVHD (HR, 2.0; P = .01), after adjusting for other predictors. Those with mismatched SIRPα had a lower relapse rate (HR, 0.6; P = .05) and significantly longer relapse-free survival (RFS; HR, 0.6; P = .04). Notably, the effect of SIRPα variant mismatch on relapse protection was most pronounced early after HSCT and in patients who were not in remission at HSCT (cumulative incidence, 73% vs 54%; HR, 0.5; P = .01). These findings show that SIRPα variant mismatch is associated with HSCT outcomes, possibly owing to innate allorecognition. SIRPα variant matching could provide valuable information for donor selection and risk stratification in HSCT.
Activation status dictates the function of unlicensed natural killer cells in mice and humans
Authors: Aguilar Ethan G. , Dunai Cordelia , Judge Sean J. , Zamora Anthony E. , Khuat Lam T. , Vick Logan V. , Collins Craig P. , Stoffel Kevin M. , Alvarez Maite , Barao Isabel , Miller Jeffrey S. , Blazar Bruce R. , Chevallier Patrice , Retiere Christelle , Canter Robert J. , Murphy William J. 
Published: September 2021

Abstract
Natural killer (NK) cells are involved in innate defense against viral infection and cancer. NK cells can be divided into subsets based on the ability of different receptors to bind to major histocompatibility (MHC) class 1 molecules, resulting in differential responses upon activation in a process called “licensing” or “arming.” NK cells expressing receptors that bind self-MHC are considered licensed due to an augmented effector lytic function capability compared with unlicensed subsets. However, we demonstrated that unlicensed NK subsets instead positively regulate the adaptive T-cell response during viral infections that are related to localization and cytokine production. In this study, the differential effects of the two types of NK subsets were contingent on the environment in viral infection and hematopoietic stem cell transplantation (HSCT) models. Infection of mice with high-dose (HD) murine cytomegalovirus (MCMC) led to a loss of licensing-associated differences, as compared with mice with low-dose (LD) infection: the unlicensed NK subset no longer localized in lymph nodes (LNs), but instead remained at the site of infection. Similarly, the patterns observed during HD infection paralleled the phenotypes of both human and mouse NK cells in an HSCT setting where NK cells exhibit an activated phenotype. However, in contrast to the effects of subset depletion in T-cell replete models, the licensed NK cell subsets still dominated antiviral responses after HSCT. Overall, our results highlight the intricate tuning of NK cells and how it affects overall immune responses with regard to licensing patterns and their dependency on the level of stimulation and activation status.
Pretransplantation EASIX predicts intensive care unit admission in allogeneic hematopoietic cell transplantation
Authors: Peña Marta , Salas Maria Queralt , Mussetti Alberto , Moreno-Gonzalez Gabriel , Bosch Anna , Patiño Beatriz , Jiménez Laura , Kara Meriem , Parody Rocío , Sureda Anna 
Published: September 2021

Abstract
The Endothelial Activation and Stress Index (EASIX) is a laboratory-based prognosis index defined as creatinine × lactate dehydrogenase/platelets. When measured at pretransplantation evaluation (EASIX-PRE), it predicts allogeneic hematopoietic cell transplantation (alloHCT) mortality. This study explores its ability to predict intensive care unit (ICU) admission and validates EASIX-PRE predictive power for overall survival (OS) and nonrelapse mortality (NRM) in 167 consecutive patients undergoing alloHCT. EASIX-PRE was calculated retrospectively in all patients and transformed into log2 values (log2-EASIX-PRE). Log2-EASIX-PRE predicted ICU admission (hazard ratio [HR], 1.41; P &lt; .001), OS (HR, 1.19; P = .011), and NRM (HR, 1.28; P = .004). The most discriminating EASIX-PRE cutoff value for risk of ICU admission was the 75th percentile (2.795); for OS and NRM, it was the median value (1.703). Patients with EASIX-PRE &gt;2.795 had higher incidence of ICU admission in comparison with patients with lower EASIX-PRE values (day +180, 35.8% vs 12.8%; HR, 2.28; P = .010). Additionally, patients with EASIX-PRE &gt;1.073 had lower OS (2 years, 57.7% vs 68.7%; HR, 1.98; P = .006) and higher NRM (2 years, 38.7% vs 18.5%; HR, 2.92; P = .001) than patients with lower EASIX-PRE results. Log2-EASIX-PRE was not associated with incidence of transplantation-associated microangiopathy, sinusoidal obstruction syndrome, or acute graft-versus-host disease. This study proposes EASIX-PRE as a prognostic tool to identify patients undergoing alloHCT at increased risk of severe organ dysfunction and who would therefore require ICU admission. Early identification of patients at high risk of severe events could contribute to personalized intervention design. Additionally, it validates the association between EASIX-PRE and OS and NRM in those undergoing alloHCT.
Fatal late-onset CAR T-cell–mediated encephalitis after axicabtagene-ciloleucel in a patient with large B-cell lymphoma
Authors: Jung Susanne , Greiner Jochen , von Harsdorf Stephanie , Popovic Pavle , Moll Roland , Schittenhelm Jens , Kandilaris Kosmas , Daniel Volker , Kunz Alexander , Schmitt Michael , Dreger Peter 
Published: September 2021

Abstract
Treatment with CD19-directed (CAR) T cells has evolved as a standard of care for multiply relapsed or refractory large B-cell lymphoma (r/r LBCL). A common side effect of this treatment is the immune effector cell–associated neurotoxicity syndrome (ICANS). Severe ICANS can occur in up to 30% to 40% of patients treated with axicabtagene-ciloleucel (axi-cel), usually within the first 4 weeks after administration of the dose and usually responding well to steroids. We describe a case of progressive central neurotoxicity occurring 9 months after axi-cel infusion in a patient with r/r LBCL who had undergone a prior allogeneic hematopoietic cell transplant. Despite extensive systemic and intrathecal immunosuppression, neurological deterioration was inexorable and eventually fatal within 5 months. High CAR T-cell DNA copy numbers and elevated levels of interleukin-1 (IL-1) and IL-6 were found in the cerebral spinal fluid as clinical symptoms emerged, and CAR T-cell brain infiltration was observed on autopsy, suggesting that CAR T cells played a major pathogenetic role. This case of unexpected, devastating, late neurotoxicity warrants intensified investigation of neurological off-target effects of CD19-directed CAR T cells and highlights the need for continuous monitoring for late toxicities in this vulnerable patient population.
MicroRNA regulation of the proliferation and apoptosis of Leydig cells in diabetes
Authors: Hu Li , Wei Shaochai , Wu Yuqi , Li Shulin , Zhu Pei , Wang Xiangwei 
Published: September 2021

Abstract
Background
The number of patients with diabetes is increasing worldwide. Diabetic testicular damage can cause spermiogenesis disorders and sexual dysfunction. We thus explored the role of miRNAs in diabetic testicular damage, and revealed that they could serve as effective prevention and treatment therapeutic targets.

Methods
Streptozotocin (STZ) was used to generate a rat model of type 2 diabetes. Rat testicular tissues were used for miRNA and mRNA sequencing. Through bioinformatics analysis, we constructed an miRNA–mRNA diabetic testicular damage regulatory network and screened for key miRNAs. We also used Leydig cells to generate a diabetic cell model and detected the downstream target genes of miRNAs, secretion of testosterone, and proliferation and apoptotic levels to elucidate the role and mechanism of the selected miRNAs in diabetic testicular damage.

Results
Using second-generation sequencing, we identified 19 differentially expressed miRNAs and 555 mRNAs in the testes of diabetic rats. Based on computational prediction of targets and negative regulation relationships, we constructed a miRNA–mRNA regulatory network, including 12 miRNAs and 215 mRNAs. KEGG enrichment analysis revealed that genes were more concentrated on the survival signalling pathway. Based on this, we screened 2 key miRNAs, miR-504 and miR-935. In vitro, glucose could induce an increase in miR-504 and miR-935, whereas a decrease in MEK5 and MEF2C in a dose-dependent manner. Overexpression of miR-504 and miR-935 led to the decreased expression of MEK5 and MEF2C, decreased proliferation rate of Leydig cells, increased apoptotic rate, and decreased secretion of testosterone. Whereas, knockdown of miR-504 and miR-935 displayed opposite tendencies.

Conclusions
miRNAs play important roles in diabetic testicular damage. miR-504 and miR-935 might regulate testicular damage through the classic survival pathway of MEK5-ERK5-MEF2C. Targeted inhibition of miR-504 and miR-935 could reverse the high-glucose-induced testicular complications, thus posing as a potential therapeutic approach in diabetic testicular injury.
Visual and somatosensory feedback mechanisms of precision manual motor control in autism spectrum disorder
Authors: Shafer Robin L. , Wang Zheng , Bartolotti James , Mosconi Matthew W. 
Published: September 2021

Abstract
Background
Individuals with autism spectrum disorder (ASD) show deficits processing sensory feedback to reactively adjust ongoing motor behaviors. Atypical reliance on visual and somatosensory feedback each have been reported during motor behaviors in ASD suggesting that impairments are not specific to one sensory domain but may instead reflect a deficit in multisensory processing, resulting in reliance on unimodal feedback. The present study tested this hypothesis by examining motor behavior across different visual and somatosensory feedback conditions during a visually guided precision grip force test.

Methods
Participants with ASD (N = 43) and age-matched typically developing (TD) controls (N = 23), ages 10–20 years, completed a test of precision gripping. They pressed on force transducers with their index finger and thumb while receiving visual feedback on a computer screen in the form of a horizontal bar that moved upwards with increased force. They were instructed to press so that the bar reached the level of a static target bar and then to hold their grip force as steadily as possible. Visual feedback was manipulated by changing the gain of the force bar. Somatosensory feedback was manipulated by applying 80 Hz tendon vibration at the wrist to disrupt the somatosensory percept. Force variability (standard deviation) and irregularity (sample entropy) were examined using multilevel linear models.

Results
While TD controls showed increased force variability with the tendon vibration on compared to off, individuals with ASD showed similar levels of force variability across tendon vibration conditions. Individuals with ASD showed stronger age-associated reductions in force variability relative to controls across conditions. The ASD group also showed greater age-associated increases in force irregularity relative to controls, especially at higher gain levels and when the tendon vibrator was turned on.

Conclusions
Our findings that disrupting somatosensory feedback did not contribute to changes in force variability or regularity among individuals with ASD suggests a reduced ability to integrate somatosensory feedback information to guide ongoing precision manual motor behavior. We also document stronger age-associated gains in force control in ASD relative to TD suggesting delayed development of multisensory feedback control of motor behavior.
A genome-wide association analysis for body weight at 35 days measured on 137,343 broiler chickens
Authors: Dadousis Christos , Somavilla Adriana , Ilska Joanna J. , Johnsson Martin , Batista Lorena , Mellanby Richard J. , Headon Denis , Gottardo Paolo , Whalen Andrew , Wilson David , Dunn Ian C. , Gorjanc Gregor , Kranis Andreas , Hickey John M. 
Published: September 2021

AbstractBackgroundBody weight (BW) is an economically important trait in the broiler (meat-type chickens) industry. Under the assumption of polygenicity, a “large” number of genes with “small” effects is expected to control BW. To detect such effects, a large sample size is required in genome-wide association studies (GWAS). Our objective was to conduct a GWAS for BW measured at 35 days of age with a large sample size.MethodsThe GWAS included 137,343 broilers spanning 15 pedigree generations and 392,295 imputed single nucleotide polymorphisms (SNPs). A false discovery rate of 1% was adopted to account for multiple testing when declaring significant SNPs. A Bayesian ridge regression model was implemented, using AlphaBayes, to estimate the contribution to the total genetic variance of each region harbouring significant SNPs (1 Mb up/downstream) and the combined regions harbouring non-significant SNPs.ResultsGWAS revealed 25 genomic regions harbouring 96 significant SNPs on 13Gallus gallusautosomes (GGA1 to 4, 8, 10 to 15, 19 and 27), with the strongest associations on GGA4 at 65.67–66.31 Mb (Galgal4 assembly). The association of these regions points to several strong candidate genes including: (i) growth factors (GGA1, 4, 8, 13 and 14); (ii) leptin receptor overlapping transcript (LEPROT)/leptin receptor (LEPR) locus (GGA8), and theSTAT3/STAT5Blocus (GGA27), in connection with the JAK/STAT signalling pathway; (iii) T-box gene (TBX3/TBX5) on GGA15 andCHST11(GGA1), which are both related to heart/skeleton development); and (iv)PLAG1(GGA2). Combined together, these 25 genomic regions explained ~ 30% of the total genetic variance. The region harbouring significant SNPs that explained the largest portion of the total genetic variance (4.37%) was on GGA4 (~ 65.67–66.31 Mb).ConclusionsTo the best of our knowledge, this is the largest GWAS that has been conducted for BW in chicken to date. In spite of the identified regions, which showed a strong association with BW, the high proportion of genetic variance attributed to regions harbouring non-significant SNPs supports the hypothesis that the genetic architecture of BW35 is polygenic and complex. Our results also suggest that a large sample size will be required for future GWAS of BW35.
Meta-analysis of the impact of plant invasions on soil microbial communities
Authors: Torres Nardi , Herrera Ileana , Fajardo Laurie , Bustamante Ramiro O. 
Published: September 2021

Abstract
Background
One of the ecological impacts of exotic plant invasions may be alteration of the soil microbial community, which may cause changes to the diversity, richness and function of these communities. In order to explore to what extent invasive plants affect the soil microbial community, we performed a meta-analysis based on 46 scientific articles to document the effect of invasive plants on species richness and diversity of bacteria and fungi. We conducted our study across a range of invaded ecosystems including native communities, and evaluated biomass, richness and diversity. We use a random effects model to determine the increase or decrease in the values of the response variables in the presence of invasive plants.

Results
The results indicated that the response variable that changed with the invasion of plants was the diversity of bacteria. Bacterial diversity in the soil increases with the presence of invasive plants, specifically herbaceous plants producing allelopathic substances growing in forest ecosystems of temperate zones.

Conclusions
We provide evidence that invasive plants affect the soil biota differentially; however, it is important to consider more variables such as the N and C cycles, since these processes are mediated by soil biota and litter, and chemical compounds released by plants influence them. Changes in bacterial diversity have consequences for the nutrient cycle, enzymatic activity, mineralization rates and soil carbon and nitrogen content.
Optimal angle of needle insertion for spinal anesthesia in patients with spondylolisthesis: an ultrasonographic study
Authors: Kim Youngwon , Yoo Seokha , Park Sun-Kyung , Bae Hansu , Lim Young-Jin , Kim Jin-Tae 
Published: September 2021

Abstract
Background
Spondylolisthesis is a common degenerative spinal deformity. At the level of spondylolisthesis, the anatomy of the interlaminar space may differ from normal spine, in which case optimal angle of the needle insertion for spinal anesthesia may change. This study compared the optimal angle of needle insertion during spinal anesthesia in patients with and without lumbar spondylolisthesis using ultrasound.

Methods
We recruited 40 patients, 20 with and 20 without lumbar spondylolisthesis (group S and N, respectively). Ultrasonography was performed in the transverse midline and parasagittal oblique views at the spondylolisthesis level and the adjacent upper level. We measured the probe application angle with the longest interlaminar height of the ligamentum flavum-dura mater complex (LFD), depth from the skin to the LFD, depth from the skin to the anterior complex, and intrathecal space width. A positive angle represented a cephalad angulation.

Results
The optimal needle insertion angle in the transverse midline view at the spondylolisthesis level was (-) 2.7 ± 3.4° in group S and 0.8 ± 2.5° in group N (P$$<$$
<
0.001). In the parasagittal oblique view, it was (-) 2.7 ± 4.5° in group S and 1.0 ± 3.2° in group N (P = 0.004). There were no between-group differences in the angles at the upper level, with all cephalad angles in both views. Other ultrasound image data were comparable between groups.

Conclusion
In patients with spondylolisthesis, caudad angulation of the spinal needle can aid successful spinal puncture at spondylolisthesis level, both in the midline and paramedian approaches.

Trial registration
www.ClinicalTrials.gov (NCT04426916); registered 11 June 2020.
Relationship between serum lipid levels and ischemic stroke in patients with atrial fibrillation: a nested case–control study based on the China Atrial Fibrillation Registry
Authors: Li Fei , Du Xin , He Liu , Jiang Chao , Xia Shijun , Ma Changsheng , Dong Jianzeng 
Published: September 2021

AbstractBackgroundAtrial fibrillation (AF) is an important risk factor for acute ischemic stroke.MethodsA nested case–control study was conducted among patients diagnosed with AF, whose information was acquired from the prospective China Atrial Fibrillation Registry (China-AF), from August 2011 to December 2018.ResultsThis study compared patients with stroke group (n = 145) with a matched control group (n = 577). Demographic data were similar except for body mass index (BMI), diastolic blood pressure (DBP) which were higher, and new oral anticoagulant (NOAC) treatment rate which was lower in the stroke group (allP < 0.05). Baseline median [IQR] levels of including triglyceride (TG) were higher in the stroke group (21.96 [16.74, 21.52], mg/dL) than the control group (19.62 [14.76, 27.36], mg/dL) (P = 0.012), while the total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were similar between the two groups. Elevated TG and HDL-C were positively associated with ischemic stroke (OR 1.01, 95% CI 1.00–1.02,P = 0.032; OR 1.03, 95% CI 1.00–1.05,P = 0.025), after adjustment for BMI, systolic blood pressure, DBP, CHA2DS2-VASc score, HAS-BLED score, NOAC, LDL-C and HDL-C. However, NOAC (OR 0.20, 95% CI 0.05–0.84,P = 0.029) could decrease the likelihood of ischemic stroke in patients with AF. In subgroup analysis, higher TG level remained significantly associated with ischemic stroke for AF patients without a history of smoking (OR 1.26, 95% CI 1.02–1.55,P = 0.028).ConclusionHigher level of TG and HDL-C were positively associated with ischemic stroke in patients with AF.
Clinical profile of bloodstream infections in COVID-19 patients: a retrospective cohort study
Authors: Palanisamy Naveenraj , Vihari Nakka , Meena Durga Shankar , Kumar Deepak , Midha Naresh , Tak Vibhor , Sharma Ankur , Bohra Gopal Krishana , Kothari Nikhil , Dutt Naveen , Bhatia Pradeep Kumar , Garg Mahendra Kumar , Misra Sanjeev 
Published: September 2021

Abstract
Background
Bloodstream infections (BSIs) are an emerging cause of significant morbidity and mortality in severe Coronavirus disease 2019 (COVID-19). We aimed to assess the prevalence, clinical profile and outcome of BSIs in critically ill COVID-19 patients.

Methods
This was a single-centre retrospective study conducted at a tertiary care hospital in Western India. All patients (age > 18 years) with reverse-transcription polymerase chain reaction (RT-PCR) confirmed COVID-19 admitted in the intensive care unit (ICU) were included. Hospital electronic records were searched for demographic data, time of bloodstream infection since admission, clinical profile, antimicrobial resistance pattern and clinical outcome of all patients who developed BSIs.

Results
Out of 750 patients admitted in COVID ICU, 8.5% developed secondary BSIs. All severe COVID-19 patients who developed BSIs succumbed to illness. A significant proportion of BSIs were Gram-negative pathogens (53/64, 82.8%). Acinetobacter baumannii was the commonest isolate, followed by Klebsiella pneumoniae (32.8% and 21.9%, respectively). Multidrug-resistance organisms (MDRO) were found in 57.8% of the cases. The majority of MDRO belonged to K. pneumoniae and Enterococcus groups. The proportion of Gram-negative bacteria resistant to carbapenems was 47.2% (25/53). On multivariate analysis, raised total leukocyte counts, mechanical ventilation and presence of comorbidities were significantly associated with the incidence of BSIs.

Conclusion
We found a significant prevalence of Acinetobacter baumannii in COVID-19 associated BSIs. The presence of comorbidities raised leukocyte counts and mechanical ventilation should alarm clinicians for possible BSIs. The timely initiation of empirical antibiotics and rapid de-escalation is vital to improve the outcome. At the same time, strict compliance of infection control practices should be accomplished to reduce the occurrence of MDRO.