bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinically-diagnosed vitamin deficiencies and disorders in the entire United States military population, 1997–2015
Authors: Knapik Joseph J. , Farina Emily K. , Fulgoni Victor L. , Lieberman Harris R. 
Published: June 2021

Abstract
Background
This study examined incidence rates, temporal trends, and demographic factors associated with vitamin deficiencies/disorders in all United States military personnel from 1997 to 2015 (mean N = 1,382,266/year).

Methods
Employing an ecological study design, the Defense Medical Epidemiological Database and specific International Classification of Diseases codes were used to determine incidence rates for clinically-diagnosed vitamin deficiencies/disorders. Associations with demographic factors were examined.

Results
The overall incidence rate of vitamin deficiencies/disorders was 92.7 cases/100,000 person-years (p-yr). Highest rates were for vitamin D (53.7 cases/100,000 p-yr), other B-complex vitamins (20.2 cases, 100,000 p-yr), vitamin B12 anemia (7.6 cases/100,000 p-yr), deficiencies of “other vitamins” (5.9 cases/100,000 p-yr), and vitamin A (2.5 cases/100,000 p-yr). Thiamin, riboflavin, niacin, pyridoxine, folate, vitamin C, and vitamin K deficiencies and hypervitaminoses A and D had < 1 case/100,000 p-yr. Rates for vitamin D, other B-complex, “other vitamin”, and thiamin deficiencies increased over time, while vitamin A and C deficiencies decreased. Women had higher incidence rates for all examined deficiencies/ disorders except niacin and vitamin C. Incidence rates rose with age in 8 of 15 deficiency/disorder categories and blacks had higher incidence rates in 9 of 15 deficiency/disorder categories.

Conclusions
The overall rate of clinically-diagnosed vitamin deficiencies and disorders was low but higher in women and minority subgroups. As for most illnesses, the diagnosed incidence of such disorders may be an underestimate of the actual incidence. These findings can guide clinical decision making with regard to testing for nutritional deficiencies and delivering public health information to at risk populations.

Clinical trial registration
(No. ISRCTN58987177). Registration date 9 October 2019.
Aspergillosis of central nervous system in patients with leukemia and stem cell transplantation: a systematic review of case reports
Authors: Shariati Aref , Didehdar Mojtaba , Rajaeih Shahin , Moradabadi Alireza , Ghorbani Mohammad , Falahati Vahid , Chegini Zahra 
Published: June 2021

Abstract
Background
Aspergillosis of Central Nervous System (CNS) is a highly lethal infection in patients with leukemia and Stem Cell Transplantation (SCT).

Methods
Case reports of CNS aspergillosis in patients with leukemia and SCT published between 1990 and August 2020 were gathered using a structured search through PubMed/Medline.

Results
Sixty-seven cases were identified over the searches of the PubMed bibliographic database and then, 59 cases were included in the final analysis. Europe had the largest share of cases at 57.6% (34 reports), followed by Americas and Asia. Affected patients were predominantly males (58.6%) and the mean age of the patients was 36.1 years, while 62.7% of the patients were under the age of 50 years. The most common leukemia types include Acute Lymphoblastic Leukemia (ALL), Chronic Lymphocytic Leukemia (CLL), and Acute Myeloid Leukemia (AML) at 43.4%, 27.4%, and 23.5%, respectively. Furthermore, stem cell transplantation was reported in 11 cases. The overall mortality was 33%; however, the attributable mortality rate of CNS aspergillosis was 24.5%. Altered mental status, hemiparesis, cranial nerve palsies, and seizures were the clearest manifestations of infection and lung involvement reported in 57% of the patients. Histopathologic examination led to the diagnosis of infection in 57% of the patients followed by culture (23.7%), galactomannan assay (8.5%), and molecular method (3.3%). Amphotericin B and voriconazole were the most frequently used drugs for infection treatment. Good results were not obtained in one-third of the patients treated by voriconazole. Finally, neurosurgical intervention was used for 23 patients (39%).

Conclusion
CNS aspergillosis is a rapidly progressive infection in leukemic patients. Thus, these patients should be followed up more carefully. Furthermore, management of induction chemotherapy, use of different diagnostic methods, and use of appropriate antifungal can lead to infection control.
Risk factors of thrombosis in Chinese subjects with acute promyelocytic leukemia
Authors: Zhang Xueya , Guo Xizhe 
Published: June 2021

Abstract
Background
Acute promyelocytic leukemia (APL) is a special type of acute myeloid leukemia Thrombosis is at increased risk complication in patients with this disease. However, the risk factors of thrombosis related to Chinese APL patients are not fully understood.

Methods
In this study, clinical and laboratory data of 44 consecutively Chinese APL patients were collected and analyzed.

Results
One arterial and 6 venous thrombosis occurred in 44 patients, including 22 males and 22 females, with a median age of 44 years (range from 18 to 74 years). The ratio of male and female gender, age, white blood cell count, hemoglobin, platelets, disease risk stratification, CD2, Khorana score, differentiation syndrome (DS) and gene mutation related to prognosis of APL, including DNMT3A, TET2, IDH1, IDH2, NRAS and ASXL1 in the two groups with and without thrombosis were not statistically significant. The detection rate of PAI-1 genotype 4G4G was 71.4% (5/7) in 7 patients with thrombosis, while the detection rate of PAI-1 genotype 4G4G in 37 patients without thrombosis was 8.1% (3/37). The differences between the two groups in WT-1 (P = 0.01), PAI-1 4G4G (P = 0.0009), bcr3 (P = 0.027), CD15 (P = 0.005), and FLT3-ITD mutation (P = 0.0008) were statistically significant. Using multivariate analysis, the risk factors of venous thrombosis in APL were CD15 (P = 0.043), PAI-1 4G4G (P = 0.009), WT-1 (P = 0.043) and FLT3/ITD (P = 0.013), respectively.

Conclusion
Our results suggested the PAI-1 gene 4G4G type, CD15, WT-1 and FLT3-ITD mutations excluding DNMT3A, TET2, IDH1/2, NRAS and ASXL1 are risk factors of thrombotic events in Chinese APL patients.
Inhibition of c-Fos expression attenuates IgE-mediated mast cell activation and allergic inflammation by counteracting an inhibitory AP1/Egr1/IL-4 axis
Authors: Wang Hui-Na , Ji Kunmei , Zhang Li-Na , Xie Chu-Chu , Li Wei-Yong , Zhao Zhen-Fu , Chen Jia-Jie 
Published: June 2021

Abstract
Background
Activator protein-1 (AP1), a c-Fos–JUN transcription factor complex, mediates many cytobiological processes. c-Fos has been implicated in immunoglobulin (Ig)E activation of mast cells (MCs) via high-affinity IgE Fc receptor (FcεRI) binding. This study examined c-Fos involvement in MC activation and tested the effects of the c-Fos/AP1 inhibitor T-5224 on MCs activation and allergic responses.

Methods
In vitro studies were conducted with two MC model systems: rat basophilic leukemia cells (RBLs) and mouse bone marrow derived mast cells (BMMCs). MC degranulation and effector functions were examined with β-hexosaminidase release and cytokine secretion assays. c-Fos/AP1 was inhibited with T-5224. c-Fos activity was suppressed with short hairpin RNA targeting c-Fos (shFos). In vivo immune responses were evaluated in passive cutaneous anaphylaxis (PCA) and ovalbumin-induced active systemic anaphylaxis (ASA) models, as well as in an oxazolone (OXA)-induced model of atopic dermatitis, a common allergic disease.

Results
c-Fos expression was elevated transcriptionally and translationally in IgE-stimulated MCs. c-Fos binding of the Egr1 (early growth response 1) promoter upregulated Egr1 transcription, leading to production of interleukin (IL)4. T-5224 reduced FcεRI-mediated MC degranulation (evidenced by β-hexosaminidase activity and histamine levels) and diminished EGR1 and IL4 expression. T-5224 attenuated IgE-mediated allergic responses in PCA and ASA models, and it suppressed MC-mediated atopic dermatitis in mice.

Conclusion
IgE binding can activate MCs via a c-Fos/Egr1/IL-4 axis. T-5224 suppresses MC activation in vitro and in vivo and thus represents a promising potential strategy for targeting MC activation to treat allergic diseases.
Microglia RAGE exacerbates the progression of neurodegeneration within the SOD1G93A murine model of amyotrophic lateral sclerosis in a sex-dependent manner
Authors: MacLean Michael , Juranek Judyta , Cuddapah Swetha , López-Díez Raquel , Ruiz Henry H. , Hu Jiyuan , Frye Laura , Li Huilin , Gugger Paul F. , Schmidt Ann Marie 
Published: June 2021

Abstract
Background
Burgeoning evidence highlights seminal roles for microglia in the pathogenesis of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). The receptor for advanced glycation end products (RAGE) binds ligands relevant to ALS that accumulate in the diseased spinal cord and RAGE has been previously implicated in the progression of ALS pathology.

Methods
We generated a novel mouse model to temporally delete Ager from microglia in the murine SOD1G93A model of ALS. Microglia Ager deficient SOD1G93A mice and controls were examined for changes in survival, motor function, gliosis, motor neuron numbers, and transcriptomic analyses of lumbar spinal cord. Furthermore, we examined bulk-RNA-sequencing transcriptomic analyses of human ALS cervical spinal cord.

Results
Transcriptomic analysis of human cervical spinal cord reveals a range of AGER expression in ALS patients, which was negatively correlated with age at disease onset and death or tracheostomy. The degree of AGER expression related to differential expression of pathways involved in extracellular matrix, lipid metabolism, and intercellular communication. Microglia display increased RAGE immunoreactivity in the spinal cords of high AGER expressing patients and in the SOD1G93A murine model of ALS vs. respective controls. We demonstrate that microglia Ager deletion at the age of symptomatic onset, day 90, in SOD1G93A mice extends survival in male but not female mice. Critically, many of the pathways identified in human ALS patients that accompanied increased AGER expression were significantly ameliorated by microglia Ager deletion in male SOD1G93A mice.

Conclusions
Our results indicate that microglia RAGE disrupts communications with cell types including astrocytes and neurons, intercellular communication pathways that divert microglia from a homeostatic to an inflammatory and tissue-injurious program. In totality, microglia RAGE contributes to the progression of SOD1G93A murine pathology in male mice and may be relevant in human disease.
How many trials are needed in kinematic analysis of reach-to-grasp?—A study of the drinking task in persons with stroke and non-disabled controls
Authors: Frykberg Gunilla Elmgren , Grip Helena , Alt Murphy Margit 
Published: June 2021

AbstractBackgroundKinematic analysis of the 3D reach-to-grasp drinking task is recommended in stroke rehabilitation research. The number of trials required to reach performance stability, as an important aspect of reliability, has not been investigated for this task. Thus, the aims of this study were to determine the number of trials needed for the drinking task to reach within-session performance stability and to investigate trends in performance over a set of trials in non-disabled people and in a sample of individuals with chronic stroke. In addition, the between-sessions test–retest reliability in persons with stroke was established.MethodsThe drinking task was performed at least 10 times, following a standardized protocol, in 44 non-disabled and 8 post-stroke individuals. A marker-based motion capture system registered arm and trunk movements during 5 pre-defined phases of the drinking task. Intra class correlation statistics were used to determine the number of trials needed to reach performance stability as well as to establish test–retest reliability. Systematic within-session trends over multiple trials were analyzed with a paired t-test.ResultsFor most of the kinematic variables 2 to 3 trials were needed to reach good performance stability in both investigated groups. More trials were needed for movement times in reaching and returning phase, movement smoothness, time to peak velocity and inter-joint-coordination. A small but significant trend of improvement in movement time over multiple trials was demonstrated in the non-disabled group, but not in the stroke group. A mean of 3 trials was sufficient to reach good to excellent test–retest reliability for most of the kinematic variables in the stroke sample.ConclusionsThis is the first study that determines the number of trials needed for good performance stability (non-disabled and stroke) and test–retest reliability (stroke) for temporal, endpoint and angular metrics of the drinking task. For most kinematic variables, 3–5 trials are sufficient to reach good reliability. This knowledge can be used to guide future kinematic studies.
Consanguinity-based analysis of exome sequencing yields likely genetic causes in patients with inherited retinal dystrophy
Authors: Shen Ren-Juan , Wang Jun-Gang , Li Yang , Jin Zi-Bing 
Published: June 2021

Abstract
Background
Consanguineous families have a relatively high prevalence of genetic disorders caused by bi-allelic mutations in recessive genes. This study aims to evaluate the effectiveness and efficiency of a consanguinity-based exome sequencing approach to capturing genetic mutations in inherited retinal dystrophy families with consanguineous marriages.

Methods
Ten unrelated consanguineous families with a proband affected by inherited retinal dystrophy were recruited in this study. All participants underwent comprehensive ophthalmic examinations. Whole exome sequencing was performed, followed by a homozygote-prior strategy to rapidly filter disease-causing mutations. Bioinformatic prediction of pathogenicity, Sanger sequencing and co-segregation analysis were carried out for further validation.

Results
In ten consanguineous families, a total of 10 homozygous mutations in 8 IRD genes were identified, including 2 novel mutations, c.1654_1655delAG (p. R552Afs*5) in gene FAM161A in a patient diagnosed with retinitis pigmentosa, and c.830T > C (p.L277P) in gene CEP78 in a patient diagnosed with cone and rod dystrophy.

Conclusion
The genetic etiology in consanguineous families with IRD were successfully identified using consanguinity-based analysis of exome sequencing data, suggesting that this approach could provide complementary insights into genetic diagnoses in consanguineous families with variant genetic disorders.
TRIM37 orchestrates renal cell carcinoma progression via histone H2A ubiquitination-dependent manner
Authors: Miao Chenkui , Liang Chao , Li Pu , Liu Bianjiang , Qin Chao , Yuan Han , Liu Yiyang , Zhu Jundong , Cui Yankang , Xu Aiming , Wang Shangqian , Su Shifeng , Li Jie , Shao Pengfei , Wang Zengjun 
Published: June 2021

AbstractBackgroundUbiquitylation modification is one of the multiple post-transcriptional process to regulate cellular physiology, including cell signaling, cycle regulation, DNA repair and transcriptional regulation. Members of TRIM family proteins could be defined as E3 ubiquitin ligases as they contain a RING-finger domain, and alterations of TRIM proteins are involved into a broad range of diverse disorders including cancer. TRIM37 is a novel discovered E3 ubiquitin ligase and acts as a oncoprotein in multiple human neoplasms, however its biological role in RCC still remains elusive.MethodsRCC microarray chips and public datasets were screened to identify novel TRIMs member as TRIM37, which was dysregulated in RCC. Gain or loss of functional cancer cell models were constructed, and in vitro and in vivo assays were performed to elucidate its tumorigenic phenotypes. Interactive network analyses were utilized to define intrinsic mechanism.ResultsWe identified TRIM37 was upregulated in RCC tumors, and its aberrant function predicted aggressive neoplastic phenotypes, poorer survival endings. TRIM37 promoted RCC cells EMT and malignant progression via TGF-β1 signaling activation, as a consequence of directly mediated by ubiquitinating-H2A modifications.ConclusionsOur findings identified a previously unappreciated role of TRIM37 in RCC progression and prognostic prediction. Importantly, we declared a novel ubiquitination-dependent link between TRIM ubiquitin ligases and TGF-β1 signaling in regulating cancerous malignancies.
MdFRK2-mediated sugar metabolism accelerates cellulose accumulation in apple and poplar
Authors: Su Jing , Zhang Chunxia , Zhu Lingcheng , Yang Nanxiang , Yang Jingjing , Ma Baiquan , Ma Fengwang , Li Mingjun 
Published: June 2021

AbstractBackgroundCellulose is not only a common component in vascular plants, but also has great economic benefits for paper, wood, and industrial products. In addition, its biosynthesis is highly regulated by carbohydrate metabolism and allocation in plant. MdFRK2, which encodes a key fructokinase (FRK) in apple, showed especially high affinity to fructose and regulated carbohydrate metabolism.ResultsIt was observed that overexpression ofMdFRK2in apple decreased sucrose (Suc) and fructose (Fru) with augmented FRK activity in stems, and caused the alterations of many phenotypic traits that include increased cellulose content and an increase in thickness of the phloem region. To further investigate the involved mechanisms, we generatedFRK2-OE poplar lines OE#1, OE#4 and OE#9 and discovered (1) that overexpression ofMdFRK2resulted in the huge increased cellulose level by shifting the fructose 6-phosphate or glucose 6-phsophate towards UDPG formation, (2) a direct metabolic pathway for the biosynthesis of cellulose is that increased cleavage of Suc into UDP-glucose (UDPG) for cellulose synthesis via the increased sucrose synthase (SUSY) activity and transcript levels ofPtrSUSY1, (3) that the increased FRK activity increases the sink strength overall so there is more carbohydrate available to fuel increased cambial activity and that resulted in more secondary phloem. These results demonstrated thatMdFRK2overexpression would significantly changes the photosynthetic carbon flux from sucrose and hexose to UDPG for increased cellulose synthesis.ConclusionsThe present data indicated thatMdFRK2overexpression in apple and poplar changes the photosynthetic carbon flux from sucrose and hexose to UDPG for stem cellulose synthesis. A strategy is proposed to increase cellulose production by regulating sugar metabolism as a whole.
Geographic distribution of the cagA, vacA, iceA, oipA and dupA genes of Helicobacter pylori strains isolated in China
Authors: Xue Zhijing , Yang Hong , Su Dongxing , Song Xiangfeng , Deng Xin , Yu Changhong , Sun Chunhua , He Lihua , You Yuanhai , Gong Yanan , Fan Dongjie , Sun Lu , Han Xiurui , Fan Ruyue , Zhang Maojun , Yan Xiaomei , Qian Jiaming , Zhang Jianzhong 
Published: June 2021

Abstract
Background
There are geographic variations in the genotypes of Helicobacter pylori (H. pylori) cagA, vacA, iceA, oipA and dupA. The aim of the study was to investigate the distribution of these genotypes among H. pylori strains from five regions of China and their association with clinical outcomes.

Materials and methods
Gastric biopsy specimens were obtained from 348 patients with different gastrointestinal diseases in the five regions of China. The regional distribution was 89 patients from Shandong, 91 from Guangxi, 57 from Hunan, 58 from Qinghai and 53 from Heilongjiang. The presence of cagA, vacA, iceA, oipA and dupA genotypes was determined by polymerase chain reaction (PCR) from H. pylori DNA.

Results
A total of 269 H. pylori isolates were obtained, of which 74 isolates were from Shandong, 78 from Guangxi, 46 from Hunan, 33 from Qinghai and 38 from Heilongjiang. The cagA-positive status was predominant in the five regions. The predominant vacA genotypes were s1c (73.4%), m2 (70.6%) and i1 (92.9%). In strains from Shandong, s1a and m1 were dominant. By contrast, s1c was dominant in Guangxi and i1 was dominant in Hunan and Heilongjiang. The prevalence of m2 subtype in Qinghai (78.8%) was significantly higher than that in other regions (P < 0.05). The predominant iceA genotype was iceA1 and the frequency of iceA1 was significantly more prevalent in Hunan than in other regions (P < 0.05). The oipA status “on” gene was more frequent in Shandong (91.9%) and Guangxi (91%) than in Heilongjiang (71.7%) (P < 0.05). Conversely, the dupA-positive status was less than half in Shandong (31.1%) and Guangxi (15.4%), whereas it was 73.9% in Hunan and 81.8% in Qinghai (P < 0.001). There were no significant associations between the cagA, vacA, iceA, oipA genotypes and clinical outcomes. The dupA-positive strains were more common in peptic ulcer disease (PUD) patients than in non-ulcer dyspepsia (NUD) patients in Shandong and Guangxi (P < 0.05), but the association was not observed in other geographic regions.

Conclusions
There was significant geographic diversity of H. pylori genotypes in different regions of China and the presence of dupA gene can be considered as a marker for the development of gastroduodenal diseases. However, the cagA, iceA, vacA and oipA genes cannot be regarded for prediction of the clinical presentation of H. pylori infection in China.
Identification and functional characterization of a fish-specific tlr19 in common carp (Cyprinus carpio L.) that recruits TRIF as an adaptor and induces ifn expression during the immune response
Authors: Shan Shijuan , Liu Rongrong , Feng Hanxiao , Meng Fei , Aizaz Muhanmmad , Yang Guiwen 
Published: June 2021

AbstractToll-like receptor 19 (Tlr19) is a fish-specific TLR that plays a critical role in innate immunity. In the present study, we aimed to identify tlr19 from common carp (Cyprinus carpio L.) and explored its expression profile, localization, adaptor, and signaling pathways. A novel tlr19 cDNA sequence (Cctlr19) was identified in common carp. Phylogenetic analysis revealed that CcTlr19 was most closely related to Danio rerio Tlr19. Subcellular localization analysis indicates that CcTlr19 was synthesized in the free ribosome and then transported to early endosomes. Cctlr19 was constitutively expressed in all the examined tissues, with the highest expression in the brain. After poly(I:C) and Aeromonas hydrophila injection, the expression of Cctlr19 was significantly upregulated in immune-related organs. In addition, the expression of Cctlr19 was upregulated in head kidney leukocytes (HKL) upon stimulation with different ligands. Immunofluorescence and luciferase analyses indicate that CcTlr19 recruited TRIF as an adaptor. Furthermore, CcTlr19 can activate the expression of ifn-1 and viperin. Taken together, these findings lay the foundation for future research to investigate the mechanisms underlying fish tlr19.
A numerical and analytical study of SE(Is)(Ih)AR epidemic fractional order COVID-19 model
Authors: Khan Hasib , Begum Razia , Abdeljawad Thabet , Khashan M. Motawi 
Published: June 2021

AbstractThis article describes the corona virus spread in a population under certain assumptions with the help of a fractional order mathematical model. The fractional order derivative is the well-known fractal fractional operator. We have given the existence results and numerical simulations with the help of the given data in the literature. Our results show similar behavior as the classical order ones. This characteristic shows the applicability and usefulness of the derivative and our numerical scheme.
Simplified and improved criteria for oscillation of delay differential equations of fourth order
Authors: Moaaz O. , Muhib A. , Baleanu D. , Alharbi W. , Mahmoud E. E. 
Published: June 2021

AbstractAn interesting point in studying the oscillatory behavior of solutions of delay differential equations is the abbreviation of the conditions that ensure the oscillation of all solutions, especially when studying the noncanonical case. Therefore, this study aims to reduce the oscillation conditions of the fourth-order delay differential equations with a noncanonical operator. Moreover, the approach used gives more accurate results when applied to some special cases, as we explained in the examples.