bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the upregulation and surface expression of hypoxanthine guanine phosphoribosyltransferase in acute lymphoblastic leukemia and Burkitt’s B cell lymphoma
Authors: Townsend Michelle H. , Ence Zac E. , Cox Taylor P. , Lattin John E. , Burrup Weston , Boyer Michael K. , Piccolo Stephen R. , Robison Richard A. , O’Neill Kim L. 
Published: August 2020

Abstract
Background
The aim of this study is to determine whether Hypoxanthine Guanine Phosphoribosyltransferase (HPRT) could be used as a biomarker for the diagnosis and treatment of B cell malignancies. With 4.3% of all new cancers diagnosed as Non-Hodgkin lymphoma, finding new biomarkers for the treatment of B cell cancers is an ongoing pursuit. HPRT is a nucleotide salvage pathway enzyme responsible for the synthesis of guanine and inosine throughout the cell cycle.

Methods
Raji cells were used for this analysis due to their high HPRT internal expression. Internal expression was evaluated utilizing western blotting and RNA sequencing. Surface localization was analyzed using flow cytometry, confocal microscopy, and membrane biotinylation. To determine the source of HPRT surface expression, a CRISPR knockdown of HPRT was generated and confirmed using western blotting. To determine clinical significance, patient blood samples were collected and analyzed for HPRT surface localization.

Results
We found surface localization of HPRT on both Raji cancer cells and in 77% of the malignant ALL samples analyzed and observed no significant expression in healthy cells. Surface expression was confirmed in Raji cells with confocal microscopy, where a direct overlap between HPRT specific antibodies and a membrane-specific dye was observed. HPRT was also detected in biotinylated membranes of Raji cells. Upon HPRT knockdown in Raji cells, we found a significant reduction in surface expression, which shows that the HPRT found on the surface originates from the cells themselves. Finally, we found that cells that had elevated levels of HPRT had a direct correlation to XRCC2, BRCA1, PIK3CA, MSH2, MSH6, WDYHV1, AK7, and BLMH expression and an inverse correlation to PRKD2, PTGS2, TCF7L2, CDH1, IL6R, MC1R, AMPD1, TLR6, and BAK1 expression. Of the 17 genes with significant correlation, 9 are involved in cellular proliferation and DNA synthesis, regulation, and repair.

Conclusions
As a surface biomarker that is found on malignant cells and not on healthy cells, HPRT could be used as a surface antigen for targeted immunotherapy. In addition, the gene correlations show that HPRT may have an additional role in regulation of cancer proliferation that has not been previously discovered.
Bismuth chelate as a contrast agent for X-ray computed tomography
Authors: Fu Ji-jun , Guo Jun-jie , Qin Ai-ping , Yu Xi-yong , Zhang Qiang , Lei Xue-ping , Huang Yu-gang , Chen Ming-yue , Li Jie-xia , Zhang Yu , Liu Jing-ping , Dang Yuan-ye , Wu Dan , Zhao Xiao-ya , Lin Zhong-xiao , Lin Yin-lei , Li Song-pei , Zhang Ling-yan 
Published: August 2020

Abstract
Backgrounds
Due to the unexpected side effects of the iodinated contrast agents, novel contrast agents for X-ray computed tomography (CT) imaging are urgently needed. Nanoparticles made by heavy metal elements are often employed, such as gold and bismuth. These nanoparticles have the advantages of long in vivo circulation time and tumor targeted ability. However, due to the long residence time in vivo, these nanoparticles may bring unexpected toxicity and, the preparation methods of these nanoparticles are complicated and time—consuming.

Methods
In this investigation, a small molecular bismuth chelate using diethylenetriaminepentaacetic acid (DPTA) as the chelating agent was proposed to be an ideal CT contrast agent.

Results
The preparation method is easy and cost—effective. Moreover, the bismuth agent show better CT imaging for kidney than iohexol in the aspect of improved CT values. Up to 500 µM, the bismuth agent show negligible toxicity to L02 cells and negligible hemolysis. And, the bismuth agent did not induce detectable morphology changes to the main organs of the mice after intravenously repeated administration at a high dose of 250 mg/kg. The pharmacokinetics of the bismuth agent follows the first—order elimination kinetics and, it has a short half—life time of 0.602 h. The rapid clearance from the body promised its excellent biocompatibility.

Conclusions
This bismuth agent may serve as a potential candidate for developing novel contrast agent for CT imaging in clinical applications.
Chitotriosidase, a biomarker of amyotrophic lateral sclerosis, accentuates neurodegeneration in spinal motor neurons through neuroinflammation
Authors: Varghese Anu Mary , Ghosh Mausam , Bhagat Savita Kumari , Vijayalakshmi K. , Preethish-Kumar Veeramani , Vengalil Seena , Chevula Pradeep-Chandra-Reddy , Nashi Saraswati , Polavarapu Kiran , Sharma Meenakshi , Dhaliwal Rupinder Singh , Philip Mariamma , Nalini Atchayaram , Alladi Phalguni Anand , Sathyaprabha Talakad N. , Raju Trichur R. 
Published: August 2020

Abstract
Background
Cerebrospinal fluid from amyotrophic lateral sclerosis patients (ALS-CSF) induces neurodegenerative changes in motor neurons and gliosis in sporadic ALS models. Search for identification of toxic factor(s) in CSF revealed an enhancement in the level and enzyme activity of chitotriosidase (CHIT-1). Here, we have investigated its upregulation in a large cohort of samples and more importantly its role in ALS pathogenesis in a rat model.

Methods
CHIT-1 level in CSF samples from ALS (n = 158), non-ALS (n = 12) and normal (n = 48) subjects were measured using ELISA. Enzyme activity was also assessed (ALS, n = 56; non-ALS, n = 10 and normal-CSF, n = 45). Recombinant CHIT-1 was intrathecally injected into Wistar rat neonates. Lumbar spinal cord sections were stained for Iba1, glial fibrillary acidic protein and choline acetyl transferase to identify microglia, astrocytes and motor neurons respectively after 48 h of injection. Levels of tumour necrosis factor-α and interleukin-6 were measured by ELISA.

Findings
CHIT-1 level in ALS-CSF samples was increased by 20-fold and it can distinguish ALS patients with a sensitivity of 87% and specificity of 83.3% at a cut off level of 1405.43 pg/ml. Enzyme activity of CHIT-1 was also 15-fold higher in ALS-CSF and has a sensitivity of 80.4% and specificity of 80% at cut off value of 0.1077989 μmol/μl/min. Combining CHIT-1 level and activity together gave a positive predictive value of 97.78% and negative predictive value of 100%. Administration of CHIT-1 increased microglial numbers and astrogliosis in the ventral horn with a concomitant increase in the levels of pro-inflammatory cytokines. Amoeboid-shaped microglial and astroglial cells were also present around the central canal. CHIT-1 administration also resulted in the reduction of motor neurons.

Conclusions
CHIT-1, an early diagnostic biomarker of sporadic ALS, activates glia priming them to attain a toxic phenotype resulting in neuroinflammation leading to motor neuronal death.
Three-dimensional models increase the interobserver agreement for the treatment of proximal humerus fractures
Authors: Cocco Luiz Fernando , Aihara André Yui , Franciozi Carlos , dos Reis Fernando Baldy , Luzo Marcus Vinicius Malheiro 
Published: August 2020

Abstract
Background
The agreement for the treatment of proximal humerus fractures is low. Interpretation of exams used for diagnosis can be directly associated with this limitation. This study proposes to compare the agreement between experts and residents in orthopedics for treatment indication of proximal humerus fractures, utilizing 3D-models, holography (augmented reality), x-rays, and tomography as diagnostic methods.

Methods
Twenty orthopedists (ten experts in shoulder and elbow surgery and ten experts in traumatology) and thirty resident physicians in orthopedics evaluated nine fractures of the proximal humerus, randomly distributed as x-rays, tomography, 3D-models and holography, using the Neer and AO / OTA Classifications. After, we evaluated the interobserver agreement between treatment options (conservative, osteosynthesis and arthroplasty) and whether the experience of the evaluators interfered with the results.

Results
The interobserver agreement analysis showed the following kappa-values: κ = 0.362 and κ = 0.306 for experts and residents (3D-models); κ = 0.240 and κ = 0.221 (X-ray); κ = 0.233 and κ = 0.123 (Tomography) and κ = 0.321 and κ = 0.160 (Holography), for experts and residents respectively. Moreover, residents and specialists were discordant in the treatment indication using Tomography as a diagnostic method (p = 0.003). The same was not seen for the other diagnostic methods (p > 0.05).

Conclusions
Three-dimensional models showed, overall, the highest interobserver agreement (experts versus residents in orthopedics) for the choice of treatment of proximal humerus fractures compared to X-ray, Tomography, and Holography. Agreement in the choice of treatment among experts that used Tomography and Holography as diagnostic methods were two times higher compared to residents.

Trial registration
Registered in Brazil Platform under no. CAAE 12273519.7.0000.5505.
Demystifying “drop-outs” in single-cell UMI data
Authors: Kim Tae Hyun , Zhou Xiang , Chen Mengjie 
Published: August 2020

AbstractMany existing pipelines for scRNA-seq data apply pre-processing steps such as normalization or imputation to account for excessive zeros or “drop-outs." Here, we extensively analyze diverse UMI data sets to show that clustering should be the foremost step of the workflow. We observe that most drop-outs disappear once cell-type heterogeneity is resolved, while imputing or normalizing heterogeneous data can introduce unwanted noise. We propose a novel framework HIPPO (Heterogeneity-Inspired Pre-Processing tOol) that leverages zero proportions to explain cellular heterogeneity and integrates feature selection with iterative clustering. HIPPO leads to downstream analysis with greater flexibility and interpretability compared to alternatives.
Long non-coding RNA cancer susceptibility candidate 2 (CASC2) alleviates the high glucose-induced injury of CIHP-1 cells via regulating miR-9-5p/PPARγ axis in diabetes nephropathy
Authors: Li Feng , Dai Bo , Ni Xiquan 
Published: August 2020

Abstract
Background
High glucose (HG) induced podocytes injury plays an important role in diabetes nephropathy (DN) development. Long noncoding RNA cancer susceptibility candidate 2 (CASC2) was found to be decreased in serum of DN patients. We aimed to explore the function and possible mechanism of CASC2 in HG induced podocytes injury.

Methods
Under normal glucose (NG), HG and mannitol stimulated podocyte conditions, the levels of CASC2, microRNA-9-5p (miR-9-5p) and peroxisome proliferator-activated receptor gamma (PPARγ) were examined by quantitative real-time polymerase chain reaction (qRT-PCR). Podocyte injury was evaluated by measuring cell viability and apoptosis of CIHP-1 cells were checked by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. Western blot was used to detect all protein levels. Dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays were performed to confirm the relationship between CASC2 and miR-9-5p.

Results
HG stimulation inhibited the expression levels of CASC2 and PPARγ, but promoted the expression of miR-9-5p. HG could restrain cell viability, autophagy and facilitate apoptosis in CIHP-1 cells, while CASC2 overexpression could reverse HG-induced podocytes injury. Furthermore, CASC2 could be used as a ceRNA to adsorb miR-9-5p, and miR-9-5p mimic overturned the effects of CASC2 on cell viability, autophagy and apoptosis in HG-stimulated podocytes. Additionally, PPARγ was a target gene of miR-9-5p, and CASC2 could weaken the HG-induced podocytes injury by up-regulating PPARγ.

Conclusion
CASC2 increased cell viability, autophagy and inhibited cell apoptosis by regulating miR-9-5p/PPARγ axis, thus reducing the HG-induced podocytes injury.
Effects of resistance training and turmeric supplementation on reactive species marker stress in diabetic rats
Authors: Júnior Ailton Santos Sena , Aidar Felipe José , Santos Jymmys Lopes Dos , Estevam Charles Dos Santos , dos Santos Jessica Denielle Matos , de Oliveira e Silva Ana Mara , Lima Fábio Bessa , De Araújo Silvan Silva , Marçal Anderson Carlos 
Published: August 2020

Abstract
Background
Type 1 diabetes mellitus (T1DM) is a metabolic disease characterized by hyperglycemia and excessive generation of reactive oxygen species caused by autoimmune destruction of beta-cells in the pancreas. Among the antioxidant compounds, Curcuma longa (CL) has potential antioxidant effects and may improve hyperglycemia in uncontrolled T1DM/TD1, as well as prevent its complications (higher costs for the maintenance of health per patient, functional disability, cardiovascular disease, and metabolic damage). In addition to the use of compounds to attenuate the effects triggered by diabetes, physical exercise is also essential for glycemic control and the maintenance of skeletal muscles. Our objective is to evaluate the effects of CL supplementation associated with moderate- to high-intensity resistance training on the parameters of body weight recovery, glycemic control, reactive species markers, and tissue damage in rats with T1DM/TD1.

Methods
Forty male 3-month-old Wistar rats (200–250 g) with alloxan-induced T1DM were divided into 4 groups (n = 7–10): sedentary diabetics (DC); diabetic rats that underwent a 4-week resistance training protocol (TD); CL-supplemented diabetic rats (200 mg/kg body weight, 3x a week) (SD); and supplemented diabetic rats under the same conditions as above and submitted to training (TSD). Body weight, blood glucose, and the following biochemical markers were analyzed: lipid profile, aspartate aminotransferase (AST), alanine aminotransferase (ALT), uric acid, creatine kinase (CK), lactate dehydrogenase (LDH), and thiobarbituric acid reactive substances (TBARS).

Results
Compared to the DC group, the TD group showed body weight gain (↑7.99%, p = 0.0153) and attenuated glycemia (↓23.14%, p = 0.0008) and total cholesterol (↓31.72%, p ≤ 0.0041) associated with diminished reactive species markers in pancreatic (↓45.53%, p < 0.0001) and cardiac tissues (↓51.85%, p < 0.0001). In addition, compared to DC, TSD promoted body weight recovery (↑15.44%, p ≤ 0.0001); attenuated glycemia (↓42.40%, p ≤ 0.0001), triglycerides (↓39.96%, p ≤ 0.001), and total cholesterol (↓28.61%, p ≤ 0.05); and attenuated the reactive species markers in the serum (↓26.92%, p ≤ 0.01), pancreas (↓46.22%, p ≤ 0.0001), cardiac (↓55.33%, p ≤ 0.001), and skeletal muscle (↓42.27%, p ≤ 0.001) tissues caused by T1DM.

Conclusion
Resistance training associated (and/or not) with the use of Curcuma longa attenuated weight loss, the hypoglycemic and hypolipidemic effects, reactive species markers, and T1DM-induced tissue injury.
A DROP-IN beta probe for robot-assisted 68Ga-PSMA radioguided surgery: first ex vivo technology evaluation using prostate cancer specimens
Authors: Collamati Francesco , van Oosterom Matthias N. , De Simoni Micol , Faccini Riccardo , Fischetti Marta , Mancini Terracciano Carlo , Mirabelli Riccardo , Moretti Roberto , Heuvel Judith olde , Solfaroli Camillocci Elena , van Beurden Florian , van der Poel Henk G. , Valdes Olmos Renato A. , van Leeuwen Pim J. , van Leeuwen Fijs W. B. , Morganti Silvio 
Published: August 2020

Background
Recently, a flexible DROP-IN gamma-probe was introduced for robot-assisted radioguided surgery, using traditional low-energy SPECT-isotopes. In parallel, a novel approach to achieve sensitive radioguidance using beta-emitting PET isotopes has been proposed. Integration of these two concepts would allow to exploit the use of PET tracers during robot-assisted tumor-receptor-targeted. In this study, we have engineered and validated the performance of a novel DROP-IN beta particle (DROP-INβ) detector.

Methods
Seven prostate cancer patients with PSMA-PET positive tumors received an additional intraoperative injection of ~ 70 MBq 68Ga-PSMA-11, followed by robot-assisted prostatectomy and extended pelvic lymph node dissection. The surgical specimens from these procedures were used to validate the performance of our DROP-INβ probe prototype, which merged a scintillating detector with a housing optimized for a 12-mm trocar and prograsp instruments.

Results
After optimization of the detector and probe housing via Monte Carlo simulations, the resulting DROP-INβ probe prototype was tested in a robotic setting. In the ex vivo setting, the probe—positioned by the robot—was able to identify 68Ga-PSMA-11 containing hot-spots in the surgical specimens: signal-to-background (S/B) was > 5 when pathology confirmed that the tumor was located < 1 mm below the specimen surface. 68Ga-PSMA-11 containing (and PET positive) lymph nodes, as found in two patients, were also confirmed with the DROP-INβ probe (S/B > 3). The rotational freedom of the DROP-IN design and the ability to manipulate the probe with the prograsp tool allowed the surgeon to perform autonomous beta-tracing.

Conclusions
This study demonstrates the feasibility of beta-radioguided surgery in a robotic context by means of a DROP-INβ detector. When translated to an in vivo setting in the future, this technique could provide a valuable tool in detecting tumor remnants on the prostate surface and in confirmation of PSMA-PET positive lymph nodes.
Overexpression of pyruvate dehydrogenase phosphatase 1 promotes the progression of pancreatic adenocarcinoma by regulating energy-related AMPK/mTOR signaling
Authors: Li Ye , Shen Jia , Cheng Chien-shan , Gao HuiFeng , Zhao Jiangang , Chen Lianyu 
Published: August 2020

Abstract
Background
Human pyruvate dehydrogenase phosphatase 1 (PDP1) plays an important physiological role in energy metabolism; however, its expression and function in human pancreatic adenocarcinoma (PDAC) remain unknown. This study aimed to investigate the expression pattern and mechanisms of action of PDP1 in human PDAC.

Methods
The expression pattern of PDP1 in PDAC was determined, and its correlation with patient survival was analyzed. Ectopic expression or knockdown of PDP1 was performed, and in vitro proliferation and migration, as well as in vivo tumor growth of PDAC, were measured. The mechanism was studied by biochemical approaches.

Results
PDP1 was overexpressed in human PDAC samples, and high expression of PDP1 correlated with poor overall and disease-free survival of PDAC patients. PDP1 promoted the proliferation, colony formation, and invasion of PDAC cells in vitro and facilitated orthotopic tumor growth in vivo. PDP1 accelerated intracellular ATP production, leading to sufficient energy to support rapid cancer progression. mTOR activation was responsible for the PDP1-induced tumor cell proliferation and invasion in PDAC. AMPK was downregulated by PDP1 overexpression, resulting in mTOR activation and cancer progression.

Conclusion
Our findings suggested that PDP1 could be a promising diagnostic and therapeutic target for anti-PDAC treatment.
Strongly extreme points of Orlicz function spaces equipped with Φ-Amemiya norm
Authors: An Lili , Cui Yunan 
Published: August 2020

AbstractIn this paper, the criterion that points of Orlicz function spaces equipped with Φ-Amemiya norm generated by an Orlicz function are strongly extreme is given. As a corollary, the sufficient and necessary conditions of midpoint local uniform rotundity of Orlicz function spaces equipped with Φ-Amemiya norm are obtained.
The spectrum of discrete Dirac operator with a general boundary condition
Authors: Coskun Nimet , Yokus Nihal 
Published: August 2020

AbstractIn this paper, we aim to investigate the spectrum of the nonselfadjoint operator L generated in the Hilbert space $l_{2}(\mathbb{N},\mathbb{C}^{2})$

l
2

(
N
,

C
2

)
by the discrete Dirac system
$$ \textstyle\begin{cases} y_{n+1}^{ (2 )} - y_{n}^{ (2 )} + p_{n} y_{n}^{ (1 )} =\lambda y_{n}^{ (1 )},\\ - y_{n}^{ (1 )} + y_{n-1}^{ (1 )} + q_{n} y_{n}^{ (2 )} =\lambda y_{n}^{ (2 )}, \end{cases}\displaystyle \quad n\in \mathbb{N}, $$

{

y

n
+
1

(
2
)

−

y
n

(
2
)

+

p
n

y
n

(
1
)

=
λ

y
n

(
1
)

,

−

y
n

(
1
)

+

y

n
−
1

(
1
)

+

q
n

y
n

(
2
)

=
λ

y
n

(
2
)

,

n
∈
N
,
and the general boundary condition
$$ \sum_{n = 0}^{\infty } h_{n}y_{n} = 0, $$

∑

n
=
0

∞

h
n

y
n

=
0
,
where λ is a spectral parameter, Δ is the forward difference operator, ($h_{n}$

h
n

) is a complex vector sequence such that $h_{n} = ( h_{n}^{(1)}, h_{n}^{(2)} )$

h
n

=
(

h
n

(
1
)

,

h
n

(
2
)

)
, where $h_{n}^{(i)} \in l^{1} ( \mathbb{N} ) \cap l^{2} ( \mathbb{N} )$

h
n

(
i
)

∈

l
1

(
N
)
∩

l
2

(
N
)
, $i = 1,2$
i
=
1
,
2
, and $h_{0}^{(1)} \ne 0$

h
0

(
1
)

≠
0
. Upon determining the sets of eigenvalues and spectral singularities of L, we prove that, under certain conditions, L has a finite number of eigenvalues and spectral singularities with finite multiplicity.
Use of medical face masks versus particulate respirators as a component of personal protective equipment for health care workers in the context of the COVID-19 pandemic
Authors: Conly John , Seto W. H. , Pittet Didier , Holmes Alison , Chu May , Hunter Paul R. ,   on behalf of the WHO Infection Prevention and Control Research and Development Expert Group for COVID-19, Conly John , Cookson Barry , Pittet Didier , Holmes Alison , Chu May , Voss Andreas , Levin Anna Sara Shafferman , Seto Wing Hong , Kalisvar Marimuthu , Fisher Dale , Gobat Nina , Hunter Paul R. , Sobsey Mark , Schwaber Mitchell J. , Tomczyk Sara , Ling Moi Lin 
Published: August 2020

AbstractCurrently available evidence supports that the predominant route of human-to-human transmission of the SARS-CoV-2 is through respiratory droplets and/or contact routes. The report by the World Health Organization (WHO) Joint Mission on Coronavirus Disease 2019 (COVID-19) in China supports person-to-person droplet and fomite transmission during close unprotected contact with the vast majority of the investigated infection clusters occurring within families, with a household secondary attack rate varying between 3 and 10%, a finding that is not consistent with airborne transmission. The reproduction number (R0) for the SARS-CoV-2 is estimated to be between 2.2–2.7, compatible with other respiratory viruses associated with a droplet/contact mode of transmission and very different than an airborne virus like measles with a R0widely cited to be between 12 and 18. Based on the scientific evidence accumulated to date, our view is that SARS-CoV-2 is not spread by the airborne route to any significant extent and the use of particulate respirators offers no advantage over medical masks as a component of personal protective equipment for the routine care of patients with COVID-19 in the health care setting. Moreover, prolonged use of particulate respirators may result in unintended harms. In conjunction with appropriate hand hygiene, personal protective equipment (PPE) used by health care workers caring for patients with COVID-19 must be used with attention to detail and precision of execution to prevent lapses in adherence and active failures in the donning and doffing of the PPE.