bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enforcing ATP hydrolysis enhanced anaerobic glycolysis and promoted solvent production in Clostridium acetobutylicum
Authors: Dai Zongjie , Zhu Yan , Dong Hongjun , Zhao Chunhua , Zhang Yanping , Li Yin 
Published: July 2021

Abstract
Background
The intracellular ATP level is an indicator of cellular energy state and plays a critical role in regulating cellular metabolism. Depletion of intracellular ATP in (facultative) aerobes can enhance glycolysis, thereby promoting end product formation. In the present study, we examined this s trategy in anaerobic ABE (acetone-butanol-ethanol) fermentation using Clostridium acetobutylicum DSM 1731.

Results
Following overexpression of atpAGD encoding the subunits of water-soluble, ATP-hydrolyzing F1-ATPase, the intracellular ATP level of 1731(pITF1) was significantly reduced compared to control 1731(pIMP1) over the entire batch fermentation. The glucose uptake was markedly enhanced, achieving a 78.8% increase of volumetric glucose utilization rate during the first 18 h. In addition, an early onset of acid re-assimilation and solventogenesis in concomitant with the decreased intracellular ATP level was evident. Consequently, the total solvent production was significantly improved with remarkable increases in yield (14.5%), titer (9.9%) and productivity (5.3%). Further genome-scale metabolic modeling revealed that many metabolic fluxes in 1731(pITF1) were significantly elevated compared to 1731(pIMP1) in acidogenic phase, including those from glycolysis, tricarboxylic cycle, and pyruvate metabolism; this indicates significant metabolic changes in response to intracellular ATP depletion.

Conclusions
In C. acetobutylicum DSM 1731, depletion of intracellular ATP significantly increased glycolytic rate, enhanced solvent production, and resulted in a wide range of metabolic changes. Our findings provide a novel strategy for engineering solvent-producing C. acetobutylicum, and many other anaerobic microbial cell factories.
Pan-cancer analysis of m5C regulator genes reveals consistent epigenetic landscape changes in multiple cancers
Authors: He Yuting , Yu Xiao , Zhang Menggang , Guo Wenzhi 
Published: July 2021

Abstract
Background
5-Methylcytosine (m5C) is a reversible modification to both DNA and various cellular RNAs. However, its roles in developing human cancers are poorly understood, including the effects of mutant m5C regulators and the outcomes of modified nucleobases in RNAs.

Methods
Based on The Cancer Genome Atlas (TCGA) database, we uncovered that mutations and copy number variations (CNVs) of m5C regulatory genes were significantly correlated across many cancer types. We then assessed the correlation between the expression of individual m5C regulators and the activity of related hallmark pathways of cancers.

Results
After validating m5C regulators’ expression based on their contributions to cancer development and progression, we observed their upregulation within tumor-specific processes. Notably, our research connected aberrant alterations to m5C regulatory genes with poor clinical outcomes among various tumors that may drive cancer pathogenesis and/or survival.

Conclusion
Our results offered strong evidence and clinical implications for the involvement of m5C regulators.
Lower response to BNT162b2 vaccine in patients with myelofibrosis compared to polycythemia vera and essential thrombocythemia
Authors: Pimpinelli Fulvia , Marchesi Francesco , Piaggio Giulia , Giannarelli Diana , Papa Elena , Falcucci Paolo , Spadea Antonio , Pontone Martina , Di Martino Simona , Laquintana Valentina , La Malfa Antonia , Di Domenico Enea Gino , Di Bella Ornella , Falzone Gianluca , Ensoli Fabrizio , Vujovic Branka , Morrone Aldo , Ciliberto Gennaro , Mengarelli Andrea 
Published: July 2021

AbstractIn a population of 42 Philadelphia negative myeloproliferative neoplasm patients, all on systemic active treatment, the likelihood of responding to anti-SARS-CoV-2 BNT162b2 vaccine at 2 weeks after the second dose was significantly lower in the ten patients with myelofibrosis compared to the 32 with essential thrombocythemia (n = 17) and polycythemia vera (n = 15) grouped together, both in terms of neutralizing anti-SARS-CoV-2 IgG titers and seroprotection rates (32.47 AU/mL vs 217.97 AU/mL, p = 0.003 and 60% vs 93.8%, p = 0.021, respectively). Ruxolitinib, which was the ongoing treatment in five patients with myelofibrosis and three with polycythemia vera, may be implicated in reducing vaccine immunogenicity (p = 0.076), though large prospective study is needed to address this issue.
Disease burden and quality of life in children with sickle cell disease in Italy: time to be considered a priority
Authors: Colombatti Raffaella , Casale Maddalena , Russo Giovanna 
Published: July 2021

AbstractThe objective of the present article is to highlight the need for attention to Quality of Life of patients with Sickle Cell Disease living in Italy. The transformation of sickle cell disease from a severe life-threatening disease of childhood into a chronic, lifelong condition due to the significant improvements in care and treatment options, imposes increasing new challenges to health care providers and patients. Patients now face physical, psychosocial and emotional challenges throughout their lives. They generally have to receive chronic treatments and regular multidisciplinary monitoring which increase social and emotional burden rendering adherence to treatment sometimes complicated. A chronic disease impacts all aspects of patients’ lives, not only the physical one, but also the social and emotional aspects as well as the educational and working life. The entire “Quality of Life” is affected and recent evidence demonstrates the importance quality of life has for patients with chronic illness. The results of this review focus on emerging data regarding quality of life across the lifespan of patients with Sickle Cell Disease, and highlight the need for more action in this field in Italy, where recent immigration and improved care determine an increasing population of children with sickle cell disease being taken into long term care.
Association between the use of balanced fluids and outcomes in critically ill children: a before and after study
Authors: Barhight Matthew F. , Nelson Delphine , Moran Thomas , Christiano Jessica , Sanchez-Pinto L. Nelson 
Published: July 2021

AbstractBackgroundHyperchloremia and chloride load have been associated with worse clinical outcomes in critically ill patients. We sought to evaluate the electrolyte profile and clinical outcomes associated with a unit-wide transition from saline to balanced fluids for resuscitation and maintenance fluids in a pediatric intensive care unit (PICU).MethodsA before and after analysis of all patients admitted to the PICU in a large, urban, academic hospital between August 2018 and March 2020. The transition from the use of saline to the use of balanced fluids for both resuscitation and maintenance fluid as standard care occurred in June 2019. The primary outcome was day 3 acute kidney injury (AKI). The secondary outcomes included mortality, ventilator-free days (VFDs), need for renal replacement therapy (RRT), hospital length of stay (LOS), and electrolyte abnormalities.ResultsOverall, 2863 patients (47% female) with a day 3 AKI rate of 12.9% (n = 130) and a mortality rate of 2.8% (n = 79) were included. After adjusting for confounders (age, PRISM III, mechanical ventilation, and immunocompromised state, septic shock), there were no significant differences in the odds of day 3 AKI (pre 13%, post 12.5%; adjusted odds ratio [aOR] 0.96, 95%CI 0.65–1.42). There were no differences in the secondary outcomes. The post-intervention period had fewer patients with hyperchloremia (pre 15.5% vs. post 10.4%,p =  < 0.0001) and hyperkalemia (pre 3.2% vs. post 1.4%,p = 0.02) and more patients with hypochloremia (pre 9.5% vs. post 14.4%,p =  < 0.0001) and hypokalemia (pre 38.2% vs. post 47.2%,p =  < 0.0001). In reference to the normochloremic cohort, the hypochloremic cohort had an increase in day 3 AKI, need for RRT, hyperchloremia, and hyperkalemia, and a decrease in hypokalemia; and the hyperchloremic cohort had an increase in VFD and a decrease in hospital LOS.ConclusionsFollowing a unit-wide implementation of balanced fluids as standard care, there were no differences in rates of day 3 AKI or other clinical outcomes. However, there were lower rates of hyperkalemia and hyperchloremia and higher rates of hypokalemia and hypochloremia. Further evaluation of the effect of balanced fluids and the clinical significance of electrolyte abnormalities in critically ill children is needed.
Genome wide DNA methylation analysis of alveolar capillary dysplasia lung tissue reveals aberrant methylation of genes involved in development including the FOXF1 locus
Authors: Slot Evelien , Boers Ruben , Boers Joachim , van IJcken Wilfred F. J. , Tibboel Dick , Gribnau Joost , Rottier Robbert , de Klein Annelies 
Published: July 2021

Abstract
Background
Alveolar capillary dysplasia with or without misalignment of the pulmonary veins (ACD/MPV) is a lethal congenital lung disorder associated with a variety of heterozygous genomic alterations in the FOXF1 gene or its 60 kb enhancer. Cases without a genomic alteration in the FOXF1 locus have been described as well. The mechanisms responsible for FOXF1 haploinsufficiency and the cause of ACD/MPV in patients without a genomic FOXF1 variant are poorly understood, complicating the search for potential therapeutic targets for ACD/MPV. To investigate the contribution of aberrant DNA methylation, genome wide methylation patterns of ACD/MPV lung tissues were compared with methylation patterns of control lung tissues using the recently developed technique Methylated DNA sequencing (MeD-seq).

Results
Eight ACD/MPV lung tissue samples and three control samples were sequenced and their mutual comparison resulted in identification of 319 differentially methylated regions (DMRs) genome wide, involving 115 protein coding genes. The potentially upregulated genes were significantly enriched in developmental signalling pathways, whereas potentially downregulated genes were mainly enriched in O-linked glycosylation. In patients with a large maternal deletion encompassing the 60 kb FOXF1 enhancer, DNA methylation patterns in this FOXF1 enhancer were not significantly different compared to controls. However, two hypermethylated regions were detected in the 60 kb FOXF1 enhancer of patients harbouring a FOXF1 point mutation. Lastly, a large hypermethylated region overlapping the first FOXF1 exon was found in one of the ACD/MPV patients without a known pathogenic FOXF1 variation.

Conclusion
This is the first study providing genome wide methylation data on lung tissue of ACD/MPV patients. DNA methylation analyses in the FOXF1 locus excludes maternal imprinting of the 60 kb FOXF1 enhancer. Hypermethylation at the 60 kb FOXF1 enhancer might contribute to FOXF1 haploinsufficiency caused by heterozygous mutations in the FOXF1 coding region. Interestingly, DNA methylation analyses of patients without a genomic FOXF1 variant suggest that abnormal hypermethylation of exon 1 might play a role in some ACD/MPV in patients.
Interplay of Val66Met and BDNF methylation: effect on reward learning and cognitive performance in major depression
Authors: Bakusic J. , Vrieze E. , Ghosh M. , Pizzagalli D. A. , Bekaert B. , Claes S. , Godderis L. 
Published: July 2021

Abstract
Background
There is a growing interest in the role of brain-derived neurotrophic factor (BDNF) in major depressive disorder (MDD). BDNF potentially exhibits opposite effects in the pathways linked to anhedonia and reward learning on the one hand and cognitive performance, on the other hand. However, the epigenetic mechanisms behind this remain unknown. In the present study, we aimed to investigate the interplay of DNA methylation of different BDNF exons and the common Val66Met polymorphism on anhedonia, reward learning and cognitive performance in MDD.

Methods
We recruited 80 depressed patients and 58 age- and gender-matched healthy controls. Participants underwent clinical assessment including neuropsychological testing and a probabilistic reward task to assess reward learning. Val66Met polymorphism and DNA methylation of BDNF promoters I, IV and exon IX were assessed from whole blood derived DNA, using pyrosequencing.

Results
BDNF promoter I methylation was lower in MDD patients (p = 0.042) and was negatively associated with self-reported anhedonia. In depressed patients, both Val66Met polymorphism and DNA methylation of promoter I were significantly associated with reward bias (p < 0.050 and p = 0.040, respectively), without an interaction effect. On the other hand, methylation of exon IX had a negative impact on executive functioning (p = 0.002) and mediated the effect of Val66Met on this outcome in patients with MDD.

Conclusions
Our results provide the first evidence of Val66Met susceptibility to differential epigenetic regulation of BDNF exons in reward learning and executive functioning in MDD, which needs to be further explored.
Multifarious functional traits of free-living rhizospheric fungi, with special reference to Aspergillus spp. isolated from North Indian soil, and their inoculation effect on plant growth
Authors: Imran Mohd , Abulreesh Hussein H. , Monjed Mohammad K. , Elbanna Khaled , Samreen  , Ahmad Iqbal 
Published: July 2021

Abstract
Purpose
Rhizospheric soil fungi are critical for plant and soil health. However, their multiple functional traits and impact on plant growth have not been systematically explored.

Methods
During this study, biochemical traits of 73 indigenous soil fungal isolates and 15 unidentified isolates related to plant growth promotion and production of extracellular enzymes were studied.

Results
Forty four (65.67%) of the total isolates produced indole acetic acid (IAA) followed by siderophore (52.23%), phosphate solubilization (37.31%), and antibiotic (11.93%). 91.04% of the studied isolates produced ammonia whereas 28.35% produced organic acid. Extracellular enzyme activities of lipase, amylase, chitinase, and cellulase were detected among 95.52%, 61.11%, 35.82%, and 41.79% isolates, respectively. Based on these activities, 73 fungal isolates were categorized into different biotypes. Quantitative analysis of IAA production and phosphate solubilization was carried out for Aspergillus, Penicillium, and Rhizopus isolates. Aspergillus isolates exhibited varying activities of IAA production and phosphate solubilization. Most of the Aspergillus isolates and some other fungi demonstrated multiple activities. Based on the multiple traits of selected fungal isolates, Aspergillus sp-07, Penicillium sp-03, and Rhizopus sp-02 were further evaluated in different combinations for their inoculation effect on the growth and yield of wheat under field conditions.

Conclusions
The results indicated that these isolates could be developed into bio-inoculants to enhance plant growth. The consortium of these three isolates was also found to be compatible and beneficial for plant growth.
Post-intensive care syndrome after a critical COVID-19: cohort study from a Belgian follow-up clinic
Authors: Rousseau Anne-Françoise , Minguet Pauline , Colson Camille , Kellens Isabelle , Chaabane Sourour , Delanaye Pierre , Cavalier Etienne , Chase J. Geoffrey , Lambermont Bernard , Misset Benoit 
Published: July 2021

Abstract
Purpose
Many patients with coronavirus disease 2019 (COVID-19) required critical care. Mid-term outcomes of the survivors need to be assessed. The objective of this single-center cohort study was to describe their physical, cognitive, psychological, and biological outcomes at 3 months following intensive care unit (ICU)-discharge (M3).

Patients and methods
All COVID-19 adults who survived an ICU stay ≥ 7 days and attended the M3 consultation at our multidisciplinary follow-up clinic were involved. They benefited from a standardized assessment, addressing health-related quality of life (EQ-5D-3L), sleep disorders (PSQI), and the three principal components of post-intensive care syndrome (PICS): physical status (Barthel index, handgrip and quadriceps strength), mental health disorders (HADS and IES-R), and cognitive impairment (MoCA). Biological parameters referred to C-reactive protein and creatinine.

Results
Among the 92 patients admitted to our ICU for COVID-19, 42 survived a prolonged ICU stay and 32 (80%) attended the M3 follow-up visit. Their median age was 62 [49–68] years, 72% were male, and nearly half received inpatient rehabilitation following ICU discharge. At M3, 87.5% (28/32) had not regained their baseline level of daily activities. Only 6.2% (2/32) fully recovered, and had normal scores for the three MoCA, IES-R and Barthel scores. The main observed disorders were PSQI > 5 (75%, 24/32), MoCA < 26 (44%, 14/32), Barthel < 100 (31%, 10/32) and IES-R ≥ 33 (28%, 9/32). Combined disorders were observed in 13/32 (40.6%) of the patients. The EQ-5D-3L visual scale was rated at 71 [61–80]. A quarter of patients (8/32) demonstrated a persistent inflammation based on CRP blood level (9.3 [6.8–17.7] mg/L).

Conclusion
The burden of severe COVID-19 and prolonged ICU stay was considerable in the present cohort after 3 months, affecting both functional status and biological parameters. These data are an argument on the need for closed follow-up for critically ill COVID-19 survivors.
Nonlinear differential equations with perturbed Dirichlet integral boundary conditions
Authors: Cabada Alberto , Iglesias Javier 
Published: July 2021

AbstractThis paper is devoted to prove the existence of positive solutions of a second order differential equation with a nonhomogeneous Dirichlet conditions given by a parameter dependence integral. The studied problem is a nonlocal perturbation of the Dirichlet conditions by considering a homogeneous Dirichlet-type condition at one extreme of the interval and an integral operator on the other one. We obtain the expression of the Green’s function related to the linear part of the equation and characterize its constant sign. Such a property will be fundamental to deduce the existence of solutions of the nonlinear problem. The results hold from fixed point theory applied to related operators defined on suitable cones.
Some properties of implicit impulsive coupled system via φ-Hilfer fractional operator
Authors: Almalahi Mohammed A. , Panchal Satish K. 
Published: July 2021

AbstractThe major goal of this work is investigating sufficient conditions for the existence and uniqueness of solutions for implicit impulsive coupled system ofφ-Hilfer fractional differential equations (FDEs) with instantaneous impulses and terminal conditions. First, we derive equivalent fractional integral equations of the proposed system. Next, by employing some standard fixed point theorems such as Leray–Schauder alternative and Banach, we obtain the existence and uniqueness of solutions. Further, by mathematical analysis technique we investigate the Ulam–Hyers (UH) and generalized UH (GUH) stability of solutions. Finally, we provide a pertinent example to corroborate the results obtained.
System of fractional boundary value problem with p-Laplacian and advanced arguments
Authors: Mahdjouba Amina , Nieto Juan J. , Ouahab Abdelghani 
Published: July 2021

AbstractIn this paper, we discuss the existence and multiplicity of positive solutions for a system of fractional differential equations with boundary condition and advanced arguments. The existence result is proved via Leray–Schauder’s fixed point theorem type in a vector Banach space. Further, by using a new fixed point theorem in order Banach space, we study the multiplicity of positive solutions. Finally, some examples are given to illustrate our results.
Donor-Derived CD7 Chimeric Antigen Receptor T Cells for T-Cell Acute Lymphoblastic Leukemia: First-in-Human, Phase I Trial
Authors: Pan Jing , Tan Yue , Wang Guoling , Deng Biping , Ling Zhuojun , Song Weiliang , Seery Samuel , Zhang Yanlei , Peng Shuixiu , Xu Jinlong , Duan Jiajia , Wang Zelin , Yu Xinjian , Zheng Qinlong , Xu Xiuwen , Yuan Ying , Yan Fangrong , Tian Zhenglong , Tang Kaiting , Zhang Jiecheng , Chang Alex H. , Feng Xiaoming 
Published: July 2021

PURPOSEPatients with relapsed or refractory T-cell acute lymphoblastic leukemia (r/r T-ALL) have few options and poor prognosis. The aim was to assess donor-derived anti-CD7 chimeric antigen receptor (CAR) T-cell safety and efficacy in patients with r/r T-ALL.METHODSIn this single-center, phase I trial, we administered anti-CD7 CAR T cells, manufactured from either previous stem-cell transplantation donors or new donors, to patients with r/r T-ALL, in single infusions at doses of 5 × 105or 1 × 106(±30%) cells per kilogram of body weight. The primary end point was safety with efficacy secondary.RESULTSTwenty participants received infusions. Adverse events including cytokine release syndrome grade 1-2 occurred in 90% (n = 18) and grade 3-4 in 10% (n = 2), cytopenia grade 3-4 in 100% (n = 20), neurotoxicity grade 1-2 in 15% (n = 3), graft-versus-host disease grade 1-2 in 60% (n = 12), and viral activation grade 1-2 in 20% (n = 4). All adverse events were reversible, except in one patient who died through pulmonary hemorrhage related to fungal pneumonia, which occurred at 5.5 months, postinfusion. Ninety percent (n = 18) achieved complete remission with seven patients proceeding to stem-cell transplantation. At a median follow-up of 6.3 months (range, 4.0-9.2), 15 remained in remission. CAR T cells were still detectable in five of five patients assessed in month 6, postinfusion. Although patients' CD7-positive normal T cells were depleted, CD7-negative T cells expanded and likely alleviated treatment-related T-cell immunodeficiency.CONCLUSIONAmong 20 patients with r/r T-ALL enrolled in this trial, donor-derived CD7 CAR T cells exhibited efficient expansion and achieved a high complete remission rate with manageable safety profile. A multicenter, phase II trial of donor-derived CD7 CAR T cells is in progress ( NCT04689659 ).
An Integrated Analysis of Dostarlimab Immunogenicity
Authors: Lu Sharon , Bowsher Ronald R. , Clancy Amanda , Rosen Amy , Zhang Mingxuan , Yang Ying , Koeck Kathleen , Gao Minggeng , Potocka Elizabeth , Guo Wei , Jen Kai Yu , Im Ellie , Milton Ashley 
Published: July 2021

AbstractMonoclonal antibodies that block the interaction between programmed cell death 1 (PD-1) and its ligand (PD-L1) have revolutionized cancer immunotherapy. However, immunogenic responses to these new therapies—such as the development of antidrug antibodies (ADAs) and neutralizing antibodies (NAbs)—may represent a significant challenge to both efficacy and safety in some patients. Dostarlimab (TSR-042) is an approved, humanized, anti-PD-1 monoclonal antibody that has shown efficacy in multiple solid tumor types. Here, we report the results of an immunogenicity analysis of dostarlimab monotherapy in patients enrolled in the GARNET trial, a multicenter, open-label, single-arm phase 1 study. Overall, 477 of 478 patients (99.8%) were included in the analysis of dostarlimab antibody prevalence, and 349 out of 478 enrolled patients (73.0%) were evaluable for treatment-emergent antibodies to dostarlimab. The incidence of treatment-emergent ADAs was 2.5% at the recommended therapeutic dose (500 mg Q3W for the first 4 doses, 1000 mg Q6W until discontinuation), which is comparable to other anti-PD-(L)1 drugs. NAbs were detected in only 1.3% of patients. In the small percentage of patients who developed ADAs, there was no evidence of altered efficacy or safety of dostarlimab at the recommended dosing regimen. These findings demonstrated that treatment with dostarlimab was associated with a low risk of eliciting clinically meaningful ADAs over the course of this study, and dostarlimab is already approved by health authorities.