bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metagenomic analysis to identify novel infectious agents in systemic anaplastic large cell lymphoma
Authors: Mahale Parag , Nomburg Jason , Song Joo Y. , Steinberg Mia , Starrett Gabriel , Boland Joseph , Lynch Charles F. , Chadburn Amy , Rubinstein Paul G. , Hernandez Brenda Y. , Weisenburger Dennis D. , Bullman Susan , Engels Eric A. 
Published: November 2021

AbstractSystemic anaplastic large cell lymphoma (ALCL) is a rare CD30-expressing T-cell non-Hodgkin lymphoma. Risk of systemic ALCL is highly increased among immunosuppressed individuals. Because risk of cancers associated with viruses is increased with immunosuppression, we conducted a metagenomic analysis of systemic ALCL to determine whether a known or novel pathogen is associated with this malignancy. Total RNA was extracted and sequenced from formalin-fixed paraffin-embedded tumor specimens from 19 systemic ALCL cases (including one case from an immunosuppressed individual with human immunodeficiency virus infection), 3 Epstein-Barr virus positive diffuse large B-cell lymphomas (DLBCLs) occurring in solid organ transplant recipients (positive controls), and 3 breast cancers (negative controls). We used a pipeline based on the Genome Analysis Toolkit (GATK)-PathSeq algorithm to subtract out human RNA reads and map the remaining RNA reads to microbes. No microbial association with ALCL was identified, but we found Epstein-Barr virus in the DLBCL positive controls and determined the breast cancers to be negative. In conclusion, we did not find a pathogen associated with systemic ALCL, but because we analyzed only one ALCL tumor from an immunosuppressed person, we cannot exclude the possibility that a pathogen is associated with some cases that arise in the setting of immunosuppression.
The terpenes camphene and alpha-bisabolol inhibit inflammatory and neuropathic pain via Cav3.2 T-type calcium channels
Authors: Gadotti Vinicius M. , Huang Sun , Zamponi Gerald W. 
Published: November 2021

AbstractT-type calcium channels are known molecular targets of certain phytocannabinoids and endocannabinoids. Here we explored the modulation of Cav3.2 T-type calcium channels by terpenes derived from cannabis plants. A screen of eight commercially available terpenes revealed that camphene and alpha-bisabolol mediated partial, but significant inhibition of Cav3.2 channels expressed in tsA-201 cells, as well as native T-type channels in mouse dorsal root ganglion neurons. Both compounds inhibited peak current amplitude with IC50s in the low micromolar range, and mediated an additional small hyperpolarizing shift in half-inactivation voltage. When delivered intrathecally, both terpenes inhibited nocifensive responses in mice that had received an intraplantar injection of formalin, with alpha-bisabolol showing greater efficacy. Both terpenes reduced thermal hyperalgesia in mice injected with Complete Freund’s adjuvant. This effect was independent of sex, and absent in Cav3.2 null mice, indicating that these compounds mediate their analgesic properties by acting on Cav3.2 channels. Both compounds also inhibited mechanical hypersensitivity in a mouse model of neuropathic pain. Hence, camphene and alpha-bisabolol have a wide spectrum of analgesic action by virtue of inhibiting Cav3.2 T-type calcium channels.
Avoidance memory requires CaMKII activity to persist after recall
Authors: Radiske Andressa , Gonzalez Maria Carolina , Rossato Janine I. , Apolinário Gênedy , de Oliveira João R. , Bevilaqua Lia R. M. , Cammarota Martín 
Published: November 2021

AbstractAvoidance memory is destabilized when recalled concurrently with conflicting information, and must undergo a hippocampus-dependent restabilization process called reconsolidation to persist. CaMKII is a serine/threonine protein kinase essential for memory processing; however, its possible involvement in avoidance memory reconsolidation has not yet been studied. Using pharmacological, electrophysiological and optogenetic tools, we found that in adult male Wistar rats hippocampal CaMKII is necessary to reconsolidate avoidance memory, but not to keep it stored while inactive, and that blocking reconsolidation via CaMKII inhibition erases learned avoidance responses.
Necrotizing enterocolitis in the preterm: newborns medical and nutritional Management in a Single-Center Study
Authors: Savarino Giovanni , Carta Maurizio , Cimador Marcello , Corsello Antonio , Giuffrè Mario , Schierz Ingrid Anne Mandy , Serra Gregorio , Corsello Giovanni 
Published: November 2021

AbstractNecrotizing enterocolitis (NEC) is a typical disorder of preterm newborns, with a high mortality and morbidity rate. The therapeutic and nutritional management of disease depends on several factors. Its prognosis is linked, in addition to the severity of the disease and the need for surgery, to a correct enteral feeding in these patients. This study aims to identify the clinical characteristics of 18 patients with NEC, evaluating the different therapeutic paths undertaken, the type of formula used and the survival rate of this population. Average time of enteral nutrition before the NEC onset was 11,3 ± 11,6 days, with an average fasting period since the onset of 24 ± 18.9 days. 77.8% of patients received surgery and resumed enteral nutrition 17.7 ± 17.9 days after the intervention. The overall survival rate of our cohort was 55.5%. More prospective studies are needed to evaluate the long-term outcomes of survived children with NEC.
Targeted high mean arterial pressure aggravates cerebral hemodynamics after extracorporeal resuscitation in swine
Authors: Levy Yael , Hutin Alice , Lidouren Fanny , Polge Nicolas , Fernandez Rocio , Kohlhauer Matthias , Leger Pierre-Louis , Debaty Guillaume , Lurie Keith , Lamhaut Lionel , Ghaleh Bijan , Tissier Renaud 
Published: November 2021

Abstract
Background
Extracorporeal cardiopulmonary resuscitation (E-CPR) is used for the treatment of refractory cardiac arrest. However, the optimal target to reach for mean arterial pressure (MAP) remains to be determined. We hypothesized that MAP levels critically modify cerebral hemodynamics during E-CPR and tested two distinct targets (65–75 vs 80–90 mmHg) in a porcine model.

Methods
Pigs were submitted to 15 min of untreated ventricular fibrillation followed by 30 min of E-CPR. Defibrillations were then delivered until return of spontaneous circulation (ROSC). Extracorporeal circulation was initially set to an average flow of 40 ml/kg/min. The dose of epinephrine was set to reach a standard or a high MAP target level (65–75 vs 80–90 mmHg, respectively). Animals were followed during 120-min after ROSC.

Results
Six animals were included in both groups. During E-CPR, high MAP improved carotid blood flow as compared to standard MAP. After ROSC, this was conversely decreased in high versus standard MAP, while intra-cranial pressure was superior. The pressure reactivity index (PRx), which is the correlation coefficient between arterial blood pressure and intracranial pressure, also demonstrated inverted patterns of alteration according to MAP levels during E-CPR and after ROSC. In standard-MAP, PRx was transiently positive during E-CPR before returning to negative values after ROSC, demonstrating a reversible alteration of cerebral autoregulation during E-CPR. In high-MAP, PRx was negative during E-CPR but became sustainably positive after ROSC, demonstrating a prolonged alteration in cerebral autoregulation after ROSC. It was associated with a significant decrease in cerebral oxygen consumption in high- versus standard-MAP after ROSC.

Conclusions
During early E-CPR, MAP target above 80 mmHg is associated with higher carotid blood flow and improved cerebral autoregulation. This pattern is inverted after ROSC with a better hemodynamic status with standard versus high-MAP.
Early prediction of hemodynamic interventions in the intensive care unit using machine learning
Authors: Rahman Asif , Chang Yale , Dong Junzi , Conroy Bryan , Natarajan Annamalai , Kinoshita Takahiro , Vicario Francesco , Frassica Joseph , Xu-Wilson Minnan 
Published: November 2021

AbstractBackgroundTimely recognition of hemodynamic instability in critically ill patients enables increased vigilance and early treatment opportunities. We develop the Hemodynamic Stability Index (HSI), which highlights situational awareness of possible hemodynamic instability occurring at the bedside and to prompt assessment for potential hemodynamic interventions.MethodsWe used an ensemble of decision trees to obtain a real-time risk score that predicts the initiation of hemodynamic interventions an hour into the future. We developed the model using the eICU Research Institute (eRI) database, based on adult ICU admissions from 2012 to 2016. A total of 208,375 ICU stays met the inclusion criteria, with 32,896 patients (prevalence = 18%) experiencing at least one instability event where they received one of the interventions during their stay. Predictors included vital signs, laboratory measurements, and ventilation settings.ResultsHSI showed significantly better performance compared to single parameters like systolic blood pressure and shock index (heart rate/systolic blood pressure) and showed good generalization across patient subgroups. HSI AUC was 0.82 and predicted 52% of all hemodynamic interventions with a lead time of 1-h with a specificity of 92%. In addition to predicting future hemodynamic interventions, our model provides confidence intervals and a ranked list of clinical features that contribute to each prediction. Importantly, HSI can use a sparse set of physiologic variables and abstains from making a prediction when the confidence is below an acceptable threshold.ConclusionsThe HSI algorithm provides a single score that summarizes hemodynamic status in real time using multiple physiologic parameters in patient monitors and electronic medical records (EMR). Importantly, HSI is designed for real-world deployment, demonstrating generalizability, strong performance under different data availability conditions, and providing model explanation in the form of feature importance and prediction confidence.
Accurate long-read de novo assembly evaluation with Inspector
Authors: Chen Yu , Zhang Yixin , Wang Amy Y. , Gao Min , Chong Zechen 
Published: November 2021

AbstractLong-read de novo genome assembly continues to advance rapidly. However, there is a lack of effective tools to accurately evaluate the assembly results, especially for structural errors. We present Inspector, a reference-free long-read de novo assembly evaluator which faithfully reports types of errors and their precise locations. Notably, Inspector can correct the assembly errors based on consensus sequences derived from raw reads covering erroneous regions. Based on in silico and long-read assembly results from multiple long-read data and assemblers, we demonstrate that in addition to providing generic metrics, Inspector can accurately identify both large-scale and small-scale assembly errors.
Fluoroquinolone susceptibility in first-line drug-susceptible M. tuberculosis isolates in Lima, Peru
Authors: Schwalb Alvaro , Cachay Rodrigo , Meza Ericka , Cáceres Tatiana , Blackman Amondrea , Maruri Fernanda , Sterling Timothy R. , Gotuzzo Eduardo 
Published: November 2021

Abstract
Objective
To determine at two distinct time points the prevalence of resistance to ofloxacin (OFX), the representative class drug of fluoroquinolones (FQs), in M. tuberculosis isolates susceptible to first-line drugs.

Results
There were 279 M. tuberculosis isolates from the two cohorts (2004–2005: 238 isolates; 2017: 41 isolates) that underwent OFX drug-susceptibility testing (critical concentration: 2 µg/ml). Of 238 isolates in Cohort 1, no resistance to OFX was detected (95% CI 0–0.016); likewise, in Cohort 2, no resistance to OFX was detected in 41 isolates (95% CI 0–0.086). Our findings suggest that FQ use remains a viable option for the treatment of first-line drug-susceptible TB in Peru.
Examining the effect of a wearable, anxiety detection technology on improving the awareness of anxiety signs in autism spectrum disorder: a pilot randomized controlled trial
Authors: Nguyen Jenny , Cardy Robyn E. , Anagnostou Evdokia , Brian Jessica , Kushki Azadeh 
Published: November 2021

Abstract
Background
Anxiety is prevalent in autism spectrum disorder (ASD) and can negatively impact physical and mental health. Self-awareness of anxiety signs is a key barrier to success of anxiety interventions for many children.

Methods
To address this, we conducted a randomized controlled trial to assess whether the Anxiety Meter, a wearable, real-time anxiety detection technology, can improve awareness of anxiety symptoms and the initiation of relaxation techniques in children with ASD. Twenty-eight children with ASD were trained on the use of the Anxiety Meter and taught a diaphragmatic breathing relaxation technique over three visits. On the fourth visit, participants were randomized to either receive feedback of their anxiety level or no feedback from the Anxiety Meter while completing a stress-eliciting task (public speaking) and asked to engage in deep breathing if anxious.

Results
Feedback from the Anxiety Meter was associated with increased likelihood of initiating deep breathing in response to anxiety.

Limitations
Limitations include the small sample size, imbalanced group matching for IQ and sex, and the controlled-laboratory settings which limit the statistical power and generalizability of the results to real-world settings.

Conclusions
Although these results are limited by the relatively small sample size, they support the feasibility of using a wearable device and real-time feedback to improve anxiety symptom awareness.
Trial Registration ClinicalTrials.gov Identifier: NCT02160691, registration date: 06/05/2014.
Bone regeneration in rat calvarial defects using dissociated or spheroid mesenchymal stromal cells in scaffold-hydrogel constructs
Authors: Shanbhag Siddharth , Suliman Salwa , Mohamed-Ahmed Samih , Kampleitner Carina , Hassan Mohamed Nageeb , Heimel Patrick , Dobsak Toni , Tangl Stefan , Bolstad Anne Isine , Mustafa Kamal 
Published: November 2021

Abstract
Background
Three-dimensional (3D) spheroid culture can promote the osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSC). 3D printing offers the possibility to produce customized scaffolds for complex bone defects. The aim of this study was to compare the potential of human BMSC cultured as 2D monolayers or 3D spheroids encapsulated in constructs of 3D-printed poly-L-lactide-co-trimethylene carbonate scaffolds and modified human platelet lysate hydrogels (PLATMC-HPLG) for bone regeneration.

Methods
PLATMC-HPLG constructs with 2D or 3D BMSC were assessed for osteogenic differentiation based on gene expression and in vitro mineralization. Subsequently, PLATMC-HPLG constructs with 2D or 3D BMSC were implanted in rat calvarial defects for 12 weeks; cell-free constructs served as controls. Bone regeneration was assessed via in vivo computed tomography (CT), ex vivo micro-CT and histology.

Results
Osteogenic gene expression was significantly enhanced in 3D versus 2D BMSC prior to, but not after, encapsulation in PLATMC-HPLG constructs. A trend for greater in vitro mineralization was observed in constructs with 3D versus 2D BMSC (p > 0.05). In vivo CT revealed comparable bone formation after 4, 8 and 12 weeks in all groups. After 12 weeks, micro-CT revealed substantial regeneration in 2D BMSC (62.47 ± 19.46%), 3D BMSC (51.01 ± 24.43%) and cell-free PLATMC-HPLG constructs (43.20 ± 30.09%) (p > 0.05). A similar trend was observed in the histological analysis.

Conclusion
Despite a trend for superior in vitro mineralization, constructs with 3D and 2D BMSC performed similarly in vivo. Regardless of monolayer or spheroid cell culture, PLATMC-HPLG constructs represent promising scaffolds for bone tissue engineering applications.
Nanog/NFATc1/Osterix signaling pathway-mediated promotion of bone formation at the tendon–bone interface after ACL reconstruction with De-BMSCs transplantation
Authors: Tie Kai , Cai Jinghang , Qin Jun , Xiao Hao , Shangguan Yangfan , Wang Hui , Chen Liaobin 
Published: November 2021

AbstractBackgroundBone formation plays an important role in early tendon–bone healing after anterior cruciate ligament reconstruction (ACLR). Dedifferentiated osteogenic bone marrow mesenchymal stem cells (De-BMSCs) have enhanced osteogenic potential. This study aimed to investigate the effect of De-BMSCs transplantation on the promotion of bone formation at the tendon–bone interface after ACLR and to further explore the molecular mechanism of the enhanced osteogenic potential of De-BMSCs.MethodsBMSCs from the femurs and tibias of New Zealand white rabbits were subjected to osteogenic induction and then cultured in medium without osteogenic factors; the obtained cell population was termed De-BMSCs. De-BMSCs were induced to undergo osteo-, chondro- and adipo-differentiation in vitro to examine the characteristics of primitive stem cells. An ACLR model with a semitendinosus tendon was established in rabbits, and the animals were divided into a control group, BMSCs group, and De-BMSCs group. At 12 weeks after surgery, the rabbits in each group were sacrificed to evaluate tendon–bone healing by histologic staining, micro-computed tomography (micro-CT) examination, and biomechanical testing. During osteogenic differentiation of De-BMSCs, an siRNA targeting nuclear factor of activated T-cells 1 (NFATc1) was used to verify the molecular mechanism of the enhanced osteogenic potential of De-BMSCs.ResultsDe-BMSCs exhibited some properties similar to BMSCs, including multiple differentiation potential and cell surface markers. Bone formation at the tendon–bone interface in the De-BMSCs group was significantly increased, and biomechanical strength was significantly improved. During the osteogenic differentiation of De-BMSCs, the expression of Nanog and NFATc1 was synergistically increased, which promoted the interaction of NFATc1 and Osterix, resulting in increased expression of osteoblast marker genes such as COL1A, OCN, and OPN.ConclusionsDe-BMSCs transplantation could promote bone formation at the tendon–bone interface after ACLR and improve the biomechanical strength of the reconstruction. The Nanog/NFATc1/Osterix signaling pathway mediated the enhanced osteogenic differentiation efficiency of De-BMSCs.
Human dental pulp stem cells attenuate streptozotocin-induced parotid gland injury in rats
Authors: Al-Serwi Rasha H. , El-Kersh Ahmed Othman Fathy Othman , El-Akabawy Gehan 
Published: November 2021

AbstractObjectiveDiabetes mellitus causes deterioration in the body, including serious damage of the oral cavity related to salivary gland dysfunction, characterised by hyposalivation and xerostomia. Human dental pulp stem cells (hDPSCs) represent a promising therapy source, due to the easy, minimally invasive surgical access to these cells and their high proliferative capacity. It was previously reported that the trophic support mediated by these cells can rescue the functional and structural alterations of damaged salivary glands. However, potential differentiation and paracrine effects of hDPSCs in diabetic-induced parotid gland damage have not been investigated. Our study aimed to investigate the therapeutic effects of intravenous transplantation of hDPSCs on parotid gland injury in a rat model of streptozotocin (STZ)-induced type 1 diabetes.MethodsThirty Sprague–Dawley male rats were randomly categorised into three groups: control, diabetic (STZ), and transplanted (STZ + hDPSCs). The hDPSCs or the vehicles were injected into the rats’ tail veins, 7 days after STZ injection. Fasting blood glucose levels were monitored weekly. A glucose tolerance test was performed, and the parotid gland weight, salivary flow rate, oxidative stress indices, parotid gland histology, and caspase-3, vascular endothelial growth factor, proliferating cell nuclear antigen, neuronal nitric oxide synthase, endothelial nitric oxide synthase, and tetrahydrobiopterin biosynthetic enzyme expression levels in parotid tissues were assessed 28 days post-transplantation.ResultsTransplantation of hDPSCs decreased blood glucose, improved parotid gland weight and salivary flow rate, and reduced oxidative stress. The cells migrated to the STZ-injured parotid gland and differentiated into acinar, ductal, and myoepithelial cells. Moreover, hDPSCs downregulated the expression of caspase-3 and upregulated the expression of vascular endothelial growth factor and proliferating cell nuclear antigen, likely exerting pro-angiogenic and anti-apoptotic effects and promoting endogenous regeneration. In addition, the transplanted cells enhanced the parotid nitric oxide-tetrahydrobiopterin pathway.ConclusionsOur results showed that hDPSCs migrated to and survived within the STZ-injured parotid gland, where functional and morphological damage was prevented due to the restoration of normal glucose levels, differentiation into parotid cell populations, and stimulation of paracrine-mediated regeneration. Thus, hDPSCs may have potential in the treatment of diabetes-induced parotid gland injury.
Molecular generation by Fast Assembly of (Deep)SMILES fragments
Authors: Berenger Francois , Tsuda Koji 
Published: November 2021

Abstract
Background
In recent years, in silico molecular design is regaining interest. To generate on a computer molecules with optimized properties, scoring functions can be coupled with a molecular generator to design novel molecules with a desired property profile.

Results
In this article, a simple method is described to generate only valid molecules at high frequency ($$>300,000$$

>
300
,
000

molecule/s using a single CPU core), given a molecular training set. The proposed method generates diverse SMILES (or DeepSMILES) encoded molecules while also showing some propensity at training set distribution matching. When working with DeepSMILES, the method reaches peak performance ($$>340,000$$

>
340
,
000

molecule/s) because it relies almost exclusively on string operations. The “Fast Assembly of SMILES Fragments” software is released as open-source at https://github.com/UnixJunkie/FASMIFRA. Experiments regarding speed, training set distribution matching, molecular diversity and benchmark against several other methods are also shown.
Optimising nutrients in the culture medium of Rhodosporidium toruloides enhances lipids production
Authors: Ye Zi , Sun Tongrui , Hao Huoye , He Yanling , Liu Xueyan , Guo Minrui , Chen Guogang 
Published: November 2021

AbstractRhodosporidium toruloides is a useful oleaginous yeast, but lipids production is affected by various factors including nutrients in the culture medium. Herein, the R-ZL2 high-yield mutant strain was used to investigate the effects of different carbon sources (sucrose, glucose, xylose), nitrogen sources (ammonium sulphate, ammonium nitrate), and C/N ratio on lipids production capacity, get the following conclusion (1) Compared with glucose and xylose, sucrose was a superior carbon source for lipids production; (2) When using ammonium sulphate as the nitrogen source, a C/N ratio of 200:1 achieved the highest biomass, lipids production and lipids content (10.7 g/L, 6.32 g/L and 59%, respectively), and lipids produced under different C/N conditions have potential for biodiesel production (except for C/N = 40 and C/N = 80); (3) When using ammonium nitrate as the nitrogen source, a C/N ratio of 200:1 achieved the highest biomass, lipids production and lipids content (12.1 g/L, 8.25 g/L and 65%, respectively), and lipids produced under different C/N ratio conditions have potential for biodiesel production. Thus, a combination of sucrose and ammonium nitrate was optimal for the lipid accumulation in R-ZL2. The findings will lay a foundation for further improving lipids yields.