Miracle-dz/UniFAR-FTUs huggingface dataset:
S100A9 promotes tumor‐associated macrophage for M2 macrophage polarization to drive human liver cancer progression: An in vitro study

Tumor‐associated macrophages (TAMs) and M2 macrophage polarization have been documented for their implication in various malignancies, but their implication in liver cancer remains to be determined. This study is intended to explore the effect of S100A9 regulated TAMs and macrophage polarization in liver cancer progression. THP‐1 cells were induced to differentiate into M1 and M2 macrophages, which were then cultured in liver cancer cell conditioned culture medium before the M1 and M2 macrophages were identified by measuring biomarkers using real‐time polymerase chain reaction. The differential expressed genes in macrophages in Gene Expression Omnibus (GEO) databases were screened. S100A9 overexpression and knockdown plasmid were transfected into macrophages to determine the effect of S100A9 on M2 macrophage polarization of TAMs and on proliferation ability of liver cancer cells. The proliferation, migration, invasion, and epithelial‐mesenchymal transition (EMT) abilities of liver cancer co‐cultured with TAMs. M1 and M2 macrophages were successfully induced and liver cancer cell conditioned culture medium can increase polarization of macrophages into M2 macrophages, in which elevated expression of S100A9 was detected. Data in GEO database showed that tumor microenvironment (TME) upregulated S1000A9 expression. Suppression on S1000A9 can significantly suppress M2 macrophage polarization. TAM can provide the necessary microenvironment for liver cancer cells, HepG2 and MHCC97H by increasing cell proliferation, migration, and invasion ability, while suppression on S1000A9 can reverse this expression pattern. Suppression on S100A9 expression can regulate M2 macrophage polarization of TAMs to suppress the progression of liver cancer.
Smartphone addiction, musculoskeletal pain and functionality in university students – a observational study

ABSTRACT Smartphone addiction and its excessive use could cause musculoskeletal symptoms such neck and upper limb pain. The purpose of this study was to investigate the association between smartphone use and musculoskeletal pain in the upper limbs and neck, as well as to observe the relationship in between smartphone addiction and musculoskeletal pain and upper limb function in university students. It is a cross-sectional, analytical study. A total of 165 university students participated in the research. Each student had their own smartphone. The students answered a structured questionnaire about pain in the upper limbs and neck; the Smartphone Addiction Inventory (SPAI) and the Disabilities of the Arm, Shoulder, and Hand questionnaire (DASH). Prevalence of neck and upper limb pain was 34.0%. Smartphone addiction and its use to play games and listen to music were risk factors to upper limb pain. Moreover, the smartphone addiction and age proved to be risk factors to neck pain. There was correlation between DASH and SPAI scores, and there was association between DASH score and neck and upper limb pain. Being of the female sex and smartphone addiction predicted the risk of incapacity development. We found association between neck and upper limb pain with smartphone addiction. Functional incapacity was associated to neck and upper limb pain. It was predicted by smartphone addiction and being of the female sex.
Analysis of Nonorthogonal $n$-Way Classifications

Four problems associated with the use of Zelen's calculus of factorials in the statistical analysis of nonorthogonal $n$-way classification data are solved. These are for the situations for which (i) some effect parameters are equated to zero, (ii) some combinations (subclasses) contain no observations, (iii) expected values of mean squares under fixed, mixed, and random models are desired, and (iv) expected values of single degree of freedom sums of squares are wanted. A unified approach to these problems was developed. Relationships to previous work, to blocked experiments, to fractional replication, and to "messy data" situations are discussed. The various analyses are first described for a nonorthogonal two-way classification and then generalized to an $n$-way classification in the final section of the paper. Numerical examples are presented to illustrate the various procedures.
Some recent developments in understanding auroral electron acceleration processes

Discrete auroral arcs and the associated inverted-V-type electron precipitation are accompanied by potential structures, upgoing ion beams and plasma density depletions in the acceleration region altitude and above. However, exactly how these phenomena depend on altitude in various Kp and solar illumination conditions as well as at various magnetic local time (MLT) and invariant latitude (ILAT) is not so well known. We review the main results of our recent large statistical studies of the altitude dependence of these parameters using Polar data. We also include similar statistical results on some additional parameters that appear to have major importance in inverted-V auroral acceleration. These parameters include middle-energy (/spl sim/50-500 eV) electron anisotropies, certain types of electrostatic wave bursts as well as ion shell distributions. One of the most interesting results of the statistical studies is that many of the parameters mentioned change their behavior rather abruptly at around 4 R/sub E/ radial distance. We draw the conclusion that the region for auroral energization processes seems to take place within a closed potential structure below /spl sim/3-4 R/sub E/. These conclusions lead to a new scenario for auroral plasma physics and the energy flow in the auroral acceleration process. The observational results are in agreement with simulations that we also summarize in this paper.
On the levitation force in horizontal core-annular flow with a large viscosity ratio and small density ratio

A numerical study has been made of horizontal core-annular flow: the flow of a high-viscosity liquid core surrounded by a low-viscosity liquid annular layer through a horizontal pipe. Special attention is paid to the question how the buoyancy force on the core, caused by a density difference between the core and the annular layer, is counterbalanced. The volume-of-fluid method is used to calculate the velocities and pressures in the two liquids. At the start of the calculation the core is in a concentric position. Thereafter the core starts to rise under the influence of buoyancy until it reaches an eccentric equilibrium position where the buoyancy force is counterbalanced by hydrodynamic forces generated by the movement of a wave at the core-annular interface with respect to the pipe wall. At high Reynolds number of the flow in the annular layer core levitation is due to inertial forces, whereas at low Reynolds number viscous (lubrication) forces are responsible for levitation. We carried out two types of calculation. In the first we assume the interface to be smooth (without wave) at the start of the calculation and study how the wave develops during the rising period of the core. In the second a wave is already present at the start of the calculation.
Clinical characteristics of patients undergoing primary bariatric surgery in the United Kingdom based on the National Bariatric Surgery Registry

Baseline demographic characteristics and operations undertaken for patients having bariatric surgery in the United Kingdom are largely unknown. This study aimed to describe the profile of patients having primary bariatric surgery in the National Health Service (NHS) or by self‐pay, and associated operations performed for both pathways. The National Bariatric Surgery Registry dataset for 5 years between January 2015 and December 2019 was used. 34 580 patients underwent primary bariatric surgery, of which 75.9% were NHS patients. Mean patient age and initial body mass index were significantly higher for NHS compared to self‐pay patients (mean age 45.8 ± 11.3 [SD] vs. 43.0 ± 12.0 years and initial body mass index 48.0 ± 7.9 vs. 42.9 ± 7.3 kg/m2, p < .001). NHS patients were more likely to have obesity‐related complications compared to self‐pay patients: prevalence of Type 2 diabetes mellitus 27.7% versus 8.3%, hypertension 37.1% versus 20.1%, obstructive sleep apnoea 27.4% versus 8.9%, severely impaired functional status 19.3% versus 13.9%, musculoskeletal pain 32.5% versus 20.1% and being on medication for depression 31.0% versus 25.9%, respectively (all p < .001). Gastric bypass was the most commonly performed primary NHS bariatric operation 57.2%, but sleeve gastrectomy predominated in self‐pay patients 48.7% (both p < .001). In contrast to self‐pay patients, NHS patients are receiving bariatric surgery only once they are older and at a much more advanced stage of obesity‐related disease complications.
Phosphodiesterase type 5 inhibitors for the treatment of sexual dysfunction in males with major depressive disorder: A systematic review and meta‐analysis

A recent meta-analysis recommended that individuals with major depressive disorder (MDD) whose acute symptoms improve with antidepressants should continue treatment to prevent relapse. 1 However, some individuals discontinue treatment, mainly due to antidepressant-associated side effects. 1,2 The side effect most likely to lead to treatment discontinuation in males in the maintenance phase is sexual dysfunction (SED). 3 MDD is associated with impairments in sexual function and satisfaction, even in untreated individuals. 3 Thus, because SED in males with MDD is a seri-ous side effect that may lead to early termination of treatment and worsen-ing of quality of life, 3 this issue is addressed in the treatment guidelines. 4,5 Phosphodiesterase type 5 inhibitors (PDE5-Is) increase vasodilation by preventing the breakdown of cyclic guanosine monophosphate, and are widely used as treatments for SED such as erectile dysfunction. 6 A previ-ous meta-analysis found that sildena ﬁ l outperformed placebo in the improvement of SED in individuals with MDD. 7 However, few of the included studies investigating SED outcomes were at the level of double-blind, randomized, placebo-controlled trials (DBRPCTs) (Table S1). To date, only eight DBRPCTs of PDE5-Is for MDD with SED have been published (Table S1). Hence, we conducted an updated systematic review and meta-analysis to determine whether PDE5-Is provide bene ﬁ ts in the treatment of SED in males with MDD. This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (Table S2). 8 The detailed methods are presented in the Open Science Framework (https://osf.io/bqm4d) and Table S2. The PICO strategy of our study was as follows: P
Glioblastoma and Other Primary Brain Malignancies in Adults: A Review.

Importance Malignant primary brain tumors cause more than 15 000 deaths per year in the United States. The annual incidence of primary malignant brain tumors is approximately 7 per 100 000 individuals and increases with age. Five-year survival is approximately 36%. Observations Approximately 49% of malignant brain tumors are glioblastomas, and 30% are diffusely infiltrating lower-grade gliomas. Other malignant brain tumors include primary central nervous system (CNS) lymphoma (7%) and malignant forms of ependymomas (3%) and meningiomas (2%). Symptoms of malignant brain tumors include headache (50%), seizures (20%-50%), neurocognitive impairment (30%-40%), and focal neurologic deficits (10%-40%). Magnetic resonance imaging before and after a gadolinium-based contrast agent is the preferred imaging modality for evaluating brain tumors. Diagnosis requires tumor biopsy with consideration of histopathological and molecular characteristics. Treatment varies by tumor type and often includes a combination of surgery, chemotherapy, and radiation. For patients with glioblastoma, the combination of temozolomide with radiotherapy improved survival when compared with radiotherapy alone (2-year survival, 27.2% vs 10.9%; 5-year survival, 9.8% vs 1.9%; hazard ratio [HR], 0.6 [95% CI, 0.5-0.7]; P < .001). In patients with anaplastic oligodendroglial tumors with 1p/19q codeletion, probable 20-year overall survival following radiotherapy without vs with the combination of procarbazine, lomustine, and vincristine was 13.6% vs 37.1% (80 patients; HR, 0.60 [95% CI, 0.35-1.03]; P = .06) in the EORTC 26951 trial and 14.9% vs 37% in the RTOG 9402 trial (125 patients; HR, 0.61 [95% CI, 0.40-0.94]; P = .02). Treatment of primary CNS lymphoma includes high-dose methotrexate-containing regimens, followed by consolidation therapy with myeloablative chemotherapy and autologous stem cell rescue, nonmyeloablative chemotherapy regimens, or whole brain radiation. Conclusions and Relevance The incidence of primary malignant brain tumors is approximately 7 per 100 000 individuals, and approximately 49% of primary malignant brain tumors are glioblastomas. Most patients die from progressive disease. First-line therapy for glioblastoma is surgery followed by radiation and the alkylating chemotherapeutic agent temozolomide.
Current Pyuria Cutoffs Promote Inappropriate Urinary Tract Infection Diagnosis in Older Women

Abstract Background Pre-existing lower urinary tract symptoms (LUTS), cognitive impairment, and the high prevalence of asymptomatic bacteriuria (ASB) complicate the diagnosis of urinary tract infection (UTI) in older women. The presence of pyuria remains the cornerstone of UTI diagnosis. However, >90% of ASB patients have pyuria, prompting unnecessary treatment. We quantified pyuria by automated microscopy and flowcytometry to determine the diagnostic accuracy for UTI and to derive pyuria thresholds for UTI in older women. Methods Women ≥65 years with ≥2 new-onset LUTS and 1 uropathogen ≥104 colony-forming units (CFU)/mL were included in the UTI group. Controls were asymptomatic and classified as ASB (1 uropathogen ≥105 CFU/mL), negative culture, or mixed flora. Patients with an indwelling catheter or antimicrobial pretreatment were excluded. Leukocyte medians were compared and sensitivity–specificity pairs were derived from a receiver operating characteristic curve. Results We included 164 participants. UTI patients had higher median urinary leukocytes compared with control patients (microscopy: 900 vs 26 leukocytes/µL; flowcytometry: 1575 vs 23 leukocytes/µL; P < .001). Area under the curve was 0.93 for both methods. At a cutoff of 264 leukocytes/µL, sensitivity and specificity of microscopy were 88% (positive and negative likelihood ratio: 7.2 and 0.1, respectively). The commonly used cutoff of 10 leukocytes/µL had a poor specificity (36%) and a sensitivity of 100%. Conclusions The degree of pyuria can help to distinguish UTI in older women from ASB and asymptomatic controls with pyuria. Current pyuria cutoffs are too low and promote inappropriate UTI diagnosis in older women. Clinical Trials Registration. International Clinical Trials Registry Platform: NL9477 (https://trialsearch.who.int/Trial2.aspx? TrialID=NL9477)
Expression of TFE3 in Cellular and Myxoid Type of Neurothekeoma: Four Cases in Young Children and Adolescents

Abstract Introduction: Cellular neurothekeoma is a benign tumor that mainly occurs in young children and adolescents. The aberrant expression of transcription factor E3 (TFE3) has not been reported in cellular neurothekeoma previously. Case report: We report four cellular neurothekeoma with aberrant immunohistochemical expression of TFE3 protein. The fluorescence in situ hybridization (FISH) showed no TFE3 gene rearrangement or amplification. Discussion/Conclusion: TEF3 protein expression may not be related to TFE3 gene translocation in cellular neurothekeoma. TFE3 may be a potential pitfall in diagnosis, for several malignant tumors in children also express TFE3. The aberrant expression of TFE3 may offer insights into cellular neurothekeoma etiology, and associated molecular mechanisms.
2‐Deoxy‐D‐glucose simultaneously targets glycolysis and Wnt/β‐catenin signaling to inhibit cervical cancer progression

Cervical cancer is one of the most common female malignant tumors, with typical cancer metabolism characteristics of increased glycolysis flux and lactate accumulation. 2‐Deoxy‐D‐glucose (2‐DG) is a glycolysis inhibitor that acts on hexokinase, the first rate‐limiting enzyme in the glycolysis pathway. In this research, we demonstrated that 2‐DG effectively reduced glycolysis and impaired mitochondrial function in cervical cancer cell lines HeLa and SiHa. Cell function experiments revealed that 2‐DG significantly inhibited cell growth, migration, and invasion, and induced G0/G1 phase arrest at non‐cytotoxic concentrations. In addition, we found that 2‐DG down‐regulated Wingless‐type (Wnt)/β‐catenin signaling. Mechanistically, 2‐DG accelerated the degradation of β‐catenin protein, which resulted in the decrease of β‐catenin expression in both nucleus and cytoplasm. The Wnt agonist lithium chloride and β‐catenin overexpression vector could partially reverse the inhibition of malignant phenotype by 2‐DG. These data suggested that 2‐DG exerted its anti‐cancer effects on cervical cancer by co‐targeting glycolysis and Wnt/β‐catenin signaling. As expected, the combination of 2‐DG and Wnt inhibitor synergistically inhibited cell growth. It is noteworthy that, down‐regulation of Wnt/β‐catenin signaling also inhibited glycolysis, indicating a similar positive feedback regulation between glycolysis and Wnt/β‐catenin signaling. In conclusion, we investigated the molecular mechanism by which 2‐DG inhibits the progression of cervical cancer in vitro, elucidated the interregulation between glycolysis and Wnt/β‐catenin signaling, and preliminarily explored the effect of combined targeting of glycolysis and Wnt/β‐catenin signaling on cell proliferation, which provides more possibilities for the formulation of subsequent clinical treatment strategies.
Customized Content Delivery for Graduate Management Education: Application to Business Statistics

Globalization is bringing about a radical “rethink” regarding the delivery of graduate management education. Today, many students entering a residential MBA program do not possess an undergraduate degree in business. As a result, many business schools are increasingly turning to the Internet to provide “customized” instructional content to ensure that students can remain competitive throughout the program. The purpose of this paper is threefold: 1) to estimate student performance in a residential MBA program; 2) to outline a process for identifying specific learning support resources based on student backgrounds and capabilities; and 3) to illustrate the screening process in providing business statistics support content to students requiring additional preparation. The results show that neural net based classification techniques can effectively identify students for the purpose of providing additional learning resources. Business statistics is one area in which this screening process has been used to deliver specialized content to students with a variety of backgrounds enrolled in a MBA residential program.
Genetic mutations in ribosomal biogenesis gene TCOF1 identified in human neural tube defects

Rare mutations in multiple genes have been associated with human neural tube defects (NTDs), but their causative roles in NTDs disease are poorly understood. Insufficiency of the ribosomal biogenesis gene treacle ribosome biogenesis factor 1(Tcof1) results in cranial NTDs and craniofacial malformations in mice. Here, we aimed to identify genetic association of TCOF1 with human NTDs.
Uncovering psychiatric phenotypes using unsupervised machine learning: A data-driven symptoms approach

Abstract Background Current categorical classification systems of psychiatric diagnoses lead to heterogeneity of symptoms within disorders and common co-occurrence of disorders. We investigated the heterogeneous and overlapping nature of symptom endorsement in a population-based sample across three of the most common categories of psychiatric disorders: depressive disorders, anxiety disorders, and sleep–wake disorders using unsupervised machine learning approaches. Methods We assessed a total of 43 symptoms in a discovery sample of 6,602 participants of the population-based Rotterdam Study between 2009 and 2013, and in a replication sample of 3,005 participants between 2016 and 2020. Symptoms were assessed using the Center for Epidemiologic Studies Depression Scale, the Hospital Anxiety and Depression Scale, and the Pittsburgh Sleep Quality Index. Hierarchical clustering analysis was applied on test items and participants to investigate common patterns of symptoms co-occurrence, and further quantitatively investigated with clustering methods to find groups that may represent similar psychiatric phenotypes. Results First, clustering analyses of the questionnaire items suggested a three-cluster solution representing clusters of “mixed” symptoms, “depressed affect and nervousness”, and “troubled sleep and interpersonal problems”. A highly similar clustering solution was independently established in the replication sample. Second, four groups of participants could be separated, and these groups scored differently on the item clusters. Conclusions We identified three clusters of psychiatric symptoms that most commonly co-occur in a population-based sample. These symptoms clustered stable over samples, but across the topics of depression, anxiety, and poor sleep. We identified four groups of participants that share (sub)clinical symptoms and might benefit from similar prevention or treatment strategies, despite potentially diverging, or lack of, diagnoses.
Dexamethasone mitigates remdesivir-induced liver toxicity in human primary hepatocytes and COVID-19 patients

Background: Coronavirus disease 2019 (COVID-19) is a global pandemic that has caused more than 600 million cases and over six million deaths worldwide. Despite the availability of vaccination, COVID-19 cases continue to grow making pharmacological interventions essential. Remdesivir (RDV) is an FDA-approved antiviral drug for treatment of both hospitalized and non-hospitalized COVID-19 patients, albeit with potential for hepatotoxicity. This study characterizes the hepatotoxicity of RDV and its interaction with dexamethasone (DEX), a corticosteroid often co-administered with RDV for inpatient treatment of COVID-19. Methods: Human primary hepatocytes and HepG2 cells were used as in vitro models for toxicity and drug-drug interaction studies. Real-world data from hospitalized COVID-19 patients were analyzed for drug-induced elevation of serum ALT and AST. Results: In cultured hepatocytes, RDV markedly reduced the hepatocyte viability and albumin synthesis, while it increased the cleavage of caspase-8 and caspase-3, phosphorylation of histone H2AX, and release of ALT and AST in a concentration-dependent manner. Importantly, co-treatment with DEX partially reversed RDV-induced cytotoxic responses in human hepatocytes. Moreover, data from COVID-19 patients treated with RDV with and without DEX co-treatment suggested that among 1037 patients matched by propensity score, receiving the drug combination was less likely to result in elevation of serum AST and ALT levels (≥ 3 × ULN) compared to the RDV alone treated patients (OR = 0.44, 95% CI = 0.22–0.92, p = 0.03). Conclusion: Our findings obtained from in vitro cell-based experiments and patient data analysis provide evidence suggesting combination of DEX and RDV holds the potential to reduce the likelihood of RDV-induced liver injury in hospitalized COVID-19 patients.