Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic Variations of DAOA (rs947267 and rs3918342) and COMT Genes (rs165599 and rs4680) in Schizophrenia and Bipolar I Disorder

Introduction: Genetic and environmental factors are involved in the incidence of schizophrenia and bipolar disorder. Many reports confirm that several common genes are connected with these two psychotic disorders. Several neurotransmitters may be involved in the molecular mechanisms of schizophrenia and bipolar disorder. We aimed to estimate the role of two talent genes: DAOA in neurotransmission of glutamate and COMT in neurotransmission of dopamine to guide the treatment of schizophrenia and bipolar disorder. Methods: Blood samples (n=100 for schizophrenia, n=100 for bipolar I disorder and n=127 for case control) were collected from individuals unrelated in the southwest of Iran. The SNPs (rs947267 and rs3918342 for DAOA gene/rs165599 and rs4680 for COMT gene) were genotyped using the PCR-RFLP method. Our finding was studied by logistic regression and Mantel-Haenszel Chi-square tests. Results: We observed an association in rs3918342, rs165599 and rs4680 single nucleotide polymorphisms and schizophrenia and bipolar I disorder. In addition, our data demonstrated that the rs947267 was related to bipolar I disorder but there was no association between this SNP and schizophrenia. Conclusion: In conclusion, this result supports the hypothesis that variations in DAOA and COMT genes may play a role in schizophrenia and bipolar disorder.
Investigations of the Hydrogen Bonds and Vibrational Spectra of Clathrate Ice XVI

Natural gas hydrates are ice-like crystalline materials formed from natural gas and clathrate ice under high pressure and low temperature. Ice XVI, the first S-II type clathrate ice produced in the lab, was simulated by first-principles density functional theory with the CASTEP code. A 34-molecule supercell was built to mimic the hydrogen-disordered structure. The vibrational spectra were calculated as a reference for inelastic neutron scattering (INS), infrared (IR) absorption, and Raman scattering experiments. Two kinds of H-bond vibration modes corresponding to two different bond strengths were found in our previous studies. In this paper, the statistics of distribution calculated by integrating these two kinds of modes was found to match the phonon density of states (PDOS) very well. We confirmed that the two basic types of H-bonds also appeared in clathrate ice XVI. The typical normal modes were analyzed to illustrate the dynamic process of lattice vibrations.
Identification of Putative UL54 (ICP27) Transcription Regulatory Sequences Binding to Oct-1, v-Myb, Pax-6 and Hairy in Herpes Simplex Viruses

An oncolytic herpes simplex virus (oHSV) has proven amenable in oncolytic virotherapy and was approved to treat melanoma. The immediate-early (IE) protein ICP27 encoded by gene UL54 is essential for HSV infection. Post-transcriptional modification of UL54 would increase tumor targeting of oHSVs. However, UL54 gene transcription regulatory sequences and factors were not reported yet. Here we isolated a new strain LXMW of type 1 HSV (HSV-1-LXMW) in China and found it's closely related to HSV-1 strains Patton and H129 in the US by the first and next generation DNA sequencing viral DNA phylogenetic analysis. Using a weight matrix-based program Match, we found the UL54 transcription regulatory sequences binding to the transcription factors Oct-1, v-Myb and Pax-6 in HSV-1-LXMW, while the sequences binding to Oct-1 and Hairy in a HSV-2 strain. Further validation showed that HSV-1 and HSV-2 shared the common sequence binding to Oct-1, but had unique sequences to bind v-Myb and Pax-6, or Hairy, respectively, by DNA sequence alignment of total 11 HSV strains. The published results howed that the expression of transcription factors is consistent with the tissue tropism of HSV-1 and HSV-2. In the current article a new HSV-1 strain LXMW was isolated and its putative HSV UL54 transcription regulatory sequences and factors were identified for the first time. Our findings highlight the new understanding of the principles of transcriptional regulation in HSV biology and oncolytic virotherapy.
Effect of Low-Frequency Vibration on Muscle Response under Different Neurointact Conditions

Stretch reflex is an important factor that influences the biomechanical response of the human body under whole-body vibration. However, there is a lack of quantitative evaluation at lower frequencies. Thus, the aim of this study was to investigate the effects of vibration on the stretch reflex and, in particular, to explore the quantitative relationship between dynamic muscle responses and low-frequency vibrations. The gastrocnemius muscle of 45 Sprague-Dawley rats was dissected. Sinusoidal vibrations of five discrete frequencies (2~16 Hz) with peak-to-peak amplitudes of 1 mm were applied to the gastrocnemius muscles with 2 mm or 3 mm prelengthening. Variables including dynamic muscle force, vibration acceleration, and displacement were recorded in two conditions, with and without the stretch reflex. Results showed that the dynamic muscle forces decreased by 20% on average for the 2 mm prelengthening group after the stretch reflex was blocked and by 24% for the 3 mm prelengthening group. Statistical analysis indicated that the amplitude of dynamic muscle force in the “with stretch reflex” condition was significantly larger than that in the “without stretch reflex” condition (p < 0.001). The tension-length curve was found to be a nonlinear hysteresis loop that changed with frequency. The phase difference between the dynamic muscle force and the length change was affected significantly by vibration frequency (p < 0.01), and the minimum frequency was 4–8 Hz. Experimental results of this study could benefit musculoskeletal model by providing a theoretical support to build a stretch reflex model for low-frequency vibration.
Complementary Function of the Meniscofemoral Ligament and Lateral Meniscus Posterior Root to Stabilize the Lateral Meniscus Posterior Horn: A Biomechanical Study in a Porcine Knee Model

Background: It has been demonstrated that the load distribution function of the lateral meniscus (LM) is compromised by resecting both the meniscofemoral ligament (MFL) and LM posterior root (LMPR). However, the effect of resecting these fibers on load transmission through the LM needs to be investigated. Purpose: To evaluate using a porcine knee model (1) the in situ forces of the MFL and LMPR and (2) the effect of resecting these fibers on the in situ force of the LM under a compressive load and valgus torque to the lateral knee compartment. Study Design: Controlled laboratory study. Methods: Twenty fresh-frozen porcine knees and a 6 degrees of freedom robotic system were utilized. An axial compressive load of 250 N and 5 N·m of valgus torque were applied to intact, MFL-deficient, LMPR-deficient, and MFL/LMPR-deficient knees at 30°, 60°, and 90° of flexion. The valgus angles under the applied loads were compared among the 4 states. The in situ forces of the MFL and LMPR under the applied loads were calculated under the principle of superposition. The in situ forces of the LM under the applied loads were also calculated and compared among the 4 conditions (intact, without the MFL, without LMPR, and without the MFL/LMPR). Results: The valgus angles significantly increased after resecting both the MFL and LMPR at all the flexion angles. The in situ forces of the MFL and LMPR changed reciprocally as the knee flexed. The in situ forces of the LM significantly decreased after resecting both the MFL and LMPR, although resecting only the MFL or LMPR represented no significant effect. Conclusion: The MFL and LMPR functioned complementarily as the posterior attachments of the LM against a compressive load and valgus torque to the lateral knee compartment in porcine knee joints. Clinical Relevance: If the LMPR is completely detached and needs to be repaired, the MFL should be preserved because it may provide some stability to the LM posterior horn and protect the repaired LMPR.
Serum AP-endonuclease 1 (sAPE1) as novel biomarker for hepatocellular carcinoma

Late diagnosis for Hepatocellular Carcinoma (HCC) remains one of the leading causes for the high mortality rate. The apurinic/apyrimidinic endonuclease 1 (APE1), an essential member of the base excision DNA repair (BER) pathway, contributes to cell response to oxidative stress and has other non-repair activities. In this study, we evaluate the role of serum APE1 (sAPE1) as a new diagnostic biomarker and we investigate the biological role for extracellular APE1 in HCC. sAPE1 level was quantified in 99 HCC patients, 50 non-HCC cirrhotic and 100 healthy controls. The expression level was significantly high in HCC (75.8 [67.3–87.9] pg/mL) compared to cirrhosis (29.8 [18.3–36.5] pg/mL] and controls (10.8 [7.5–13.2] pg/mL) (p < 0.001). The sAPE1 level corresponded with its protein expression in HCC tissue. sAPE1 had high diagnostic accuracy to differentiate HCC from cirrhotic (AUC = 0.87, sensitivity 88%, specificity 71%, cut-off of 36.3 pg/mL) and healthy subjects (AUC 0.98, sensibility 98% and specificity 83%, cut-off of 19.0 pg/mL). Recombinant APE1, exogenously added to JHH6 cells, significantly promotes IL-6 and IL-8 expression, suggesting a role of sAPE1 as a paracrine pro-inflammatory molecule, which may modulate the inflammatory status in cancer microenvironment. We described herein, for the first time to our knowledge, that sAPE1 might be considered as a promising diagnostic biomarker for HCC.
Moxibustion of Zusanli (ST36) and Shenshu (BL23) Alleviates Cartilage Degradation through RANKL/OPG Signaling in a Rabbit Model of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a systemic and chronic autoimmune inflammatory disease characterized by severe synovial hyperplasia associated with progressive cartilage degradation. Due to the severe pain and disability caused by RA, effective therapeutic strategies that could simultaneously alleviate the inflammatory response and delay the disease progression are urgently needed. As a major alternative therapy in traditional Chinese medicine, moxibustion has been demonstrated that it could reduce the chronic inflammatory responses of a series of musculoskeletal diseases; however, whether moxibustion has protective effects on RA is still unclear. To investigate the effects of moxibustion on RA, moxibustion was applied to Zusanli (ST36) and Shenshu (BL23) acupoints in a RA rabbit model. HE staining of articular cartilage showed that moxibustion alleviated the cartilage degradation and bone destruction. In addition, moxibustion decreased the osteoclast number in RA rabbits. Real-time PCR revealed that moxibustion decreased the expression of RANKL mRNA while increased the expression of OPG mRNA, indicating a restoration of the balance between osteogenesis and osteoclastogenesis. Taken together, our results indicated that moxibustion had promising antiarthritic effects and could be an useful alternative method in RA therapeutics.
Nomogram for predicting level V lymph node metastases in papillary thyroid carcinoma with clinically lateral lymph node metastases: A large retrospective cohort study of 1037 patients from FDUSCC

Objective: Extensive lateral neck dissection (LND), especially routine level V dissection, may potentially increase morbidity and have no significant benefit to survival in patients with papillary thyroid carcinoma (PTC). Our study aimed to determine the pattern and risk factors for level V lymph node metastasis (LNM) and to develop an assessment model based on a nomogram for predicting whether level V dissection is necessary. Methods: A total of 1037 PTC patients with clinically suspected LNM (N1b) who underwent total thyroidectomy (TT) with central LND and unilateral LND from 2011 to 2015 were retrospectively retrieved. Univariate and multivariate analyses were performed to examine risk factors associated with level V metastasis. A nomogram for predicting level V metastasis was established and internally validated. Results: The overall rate of level V metastasis was 21.3% (221/1037). Unilateral central LNM (CLNM), level II/III/IV metastasis, extra nodal extension (ENE) and lymph node (LN) size ≥2 cm were found to be independent predictive factors for level V metastasis (P<0.05). In the nomogram, ENE was confirmed as the largest contributor to scores, followed by LN size, unilateral CLNM and level IV/III/II metastasis. The discrimination of the prediction model was 0.738 (95% confidence interval (CI): 0.703-0.773, P<0.001). Conclusions: The rate of level V metastasis in N1b PTC patients was apparently lower than that of other levels. With the help of our nomogram, a modified lateral neck dissection encompassing levels II-V and a strictly postoperative evaluation may be indicated when the patient has a high score.
Influence of nasal polyp tissue on the differentiation and activation of T lymphocytes in a co-culture system

T cell subpopulations in nasal polyps differ from peripheral lymphocytes in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). However, little is known about the modulatory influence of the inflamed nasal polyp epithelial cells on the phenotype of the T cells. The aim of the present study was to assess this interaction. Tissue and blood samples were collected from 16 patients undergoing paranasal sinus surgery. Polypoid tissue was cultured under air-liquid interface conditions. Subsequently, cluster of differentiation (CD)3/CD28 activated peripheral lymphocytes from the same patients were added. After 3 days lymphocytes were separated from co-culture and analyzed by multicolor flow cytometry. Additionally, cytokine expression of the polyp tissue was measured using a human T helper cell (TH)1/TH2/TH17 antibody array. Viability staining of CD3+ lymphocytes detected fewer apoptotic cells under co-culture conditions compared with in mono-culture. There was a significantly higher frequency of CD4+ and CD8+ T cells in the co-culture system than in PBMC culture alone. Human leukocyte antigen (HLA)-DR isotype was significantly downregulated on co-cultured CD3+ lymphocytes and CD3+CD4+ T cells compared with the mono-cultured counterparts. Conventional Forkhead box P3- memory CD4+ T cells and activated regulatory T cells increased in frequency, and resting regulatory T cells decreased in the co-culture. Cytokine analysis identified expression of interleukin (IL)-6, IL-6 receptor, granulocyte-macrophage colony-stimulating factor, transforming growth factor-β and macrophage inflammatory protein-3 in the polyp tissue. In summary, the present study performed a comparison between peripheral lymphocytes cultured with and without nasal polyp tissue cells was performed. The downregulation of HLA and the differentiation of Treg and Tconv by nasal polypoid tissue on PBMCs was demonstrated. Interestingly, the in vivo downregulation of HLA-DR on CD3+ lymphocytes, as reported previously, was confirmed in vitro. The inhibitory effect of polypoid tissue on the activation of lymphocytes is a possible pathogenic mechanism underlying CRSwNP.
Kp-series and varieties generated by wreath products of p-groups

Let [Formula: see text] be a nilpotent [Formula: see text]-group of finite exponent and [Formula: see text] be an abelian [Formula: see text]-group of finite exponent for a given prime number [Formula: see text]. Then the wreath product [Formula: see text] generates the variety [Formula: see text] if and only if the group [Formula: see text] contains a subgroup isomorphic to the direct product [Formula: see text] of countably many copies of the cycle [Formula: see text] of order [Formula: see text]. The obtained theorem continues our previous study of cases when [Formula: see text] holds for some other classes of groups [Formula: see text] and [Formula: see text] (abelian groups, finite groups, etc.).
Child Development and Nutritional Status in Ecuador

We assessed the development, nutritional status, and complementary feeding of 12- to 23-month-old children from Cuenca, Ecuador in 2013. Ecuador, an upper-middle-income country, developed a child policy in accordance with World Health Organization (WHO) guidelines. We collected cross-sectional survey data. Child development was assessed using the Integrated Management of Childhood Illness Guide–2011. The nutritional status was defined with WHO Child Growth Standards−2006. We investigated nutrient density, WHO Infant and Young Child Feeding Indicators, and nutrient supplementation intake of the complementary feeding. In all, 11.7% of children had “possible developmental delay,” stunting was identified in 29.4% of the children, and 25.3% faced overnutrition (overweight risk/overweight/obesity). The complementary feeding composition can be summarized as having adequate fat, high energy (MJ/day) and protein, and low iron and zinc. Children with “possible developmental delay” received less iron (P < .05) than children with normal development. Overall, 30.4% of children had minimum dietary diversity. A total of 47.7% of children received nutrient supplementation. This epidemiological profile of infants remains a challenge for Ecuador’s health programs.
The Role of Infection in Acute Exacerbation of Idiopathic Pulmonary Fibrosis

Background Acute exacerbation of IPF (AE-IPF) is associated with high mortality. We studied changes in pathogen involvement during AE-IPF and explored a possible role of infection in AE-IPF. Objectives Our purpose is to investigate the role of infection in AE-IPF. Methods Overall, we recruited 170 IPF patients (48 AE-IPF, 122 stable) and 70 controls at Shanghai Pulmonary Hospital. Specific IgM against microbial pathogens and pathogens in sputum were assessed. RNA sequences of pathogens in nasopharyngeal swab of IPF patients were detected by PathChip. A panel of serum parameters reflecting immune function were assessed. Results Antiviral/bacterial IgM was higher in IPF vs. controls and in AE-IPF vs. stable IPF. Thirty-eight different bacterial strains were detected in IPF patient sputum. Bacteria-positive results were found in 9/48 (18.8%) of AE-IPF and in 26/122 (21.3%) stable IPF. Fifty-seven different viruses were detected in nasopharyngeal swabs of IPF patients. Virus-positive nasopharyngeal swabs were found in 18/30 (60%) of tested AE-IPF and in 13/30 (43.3%) of stable IPF. AE-IPF showed increased inflammatory cytokines (IL-6, IFN-γ, MIG, IL-17, and IL-9) vs. stable IPF and controls. Mortality of AE-IPF in one year (39.5%) was higher compared to stable IPF (28.7%). Conclusions. IPF patients had different colonization with pathogens in sputum and nasopharyngeal swabs; they also displayed abnormally activated immune response, which was exacerbated during AE-IPF.
Loss of Yes-associated Protein Represents an Aggressive Subtype of Colorectal Cancer

Background: Yes-associated protein (YAP) is a downstream effecter of Hippo signaling pathway, and has been linked to the initiation and development of colorectal cancer (CRC). However, the clinical significance of YAP in CRC remains controversial. This study was designed to investigate the clinical significance of YAP in CRC. Methods: We selected 206 eligible patients diagnosed with CRC from 2003 to 2007. Tissue microarray (TMA) blocks were made from 206 formalin-fixed paraffin-embedded CRC tissues and 158 corresponding normal colonic tissues. Using the TMA blocks, we performed immunohistochemical staining of YAP and assessed its expression status in different subcellular locations. The patients were divided into four groups according to the expression status of YAP in the cytoplasm and nucleus. Statistical analysis was performed to explore the correlation between YAP expression and clinicopathological features and overall survival (OS) in CRC patients. Results: Our results showed that both cytoplasmic YAP and nuclear YAP were overexpressed in CRC tissues compared to normal colonic tissues. Complete loss of YAP expression in CRC was significantly correlated with larger tumor size (p=0.023), proximal tumor location (p=0.038), higher tumor grade (p=0.022) and worse OS (p<0.001). Univariate and multivariate Cox regression analyses revealed that complete loss of YAP expression was an independent indicator of poor prognosis in CRC (p<0.001). Conclusions: Loss of YAP expression correlates with poor prognosis and may represent a subgroup with more aggressive biological features in CRC.
Effect of Co-administration of Bumetanide and Phenobarbital on Seizure Attacks in Temporal Lobe Epilepsy

Introduction: The resistance of temporal lobe epilepsy to classic drugs is thought to be due to disruption in the excitation/inhibition of this pathway. Two chloride transporters, NKCC1 and KCC2, are expressed differently for the excitatory state of Gamma-Amino Butyric Acid (GABA). The present study explored the effect of bumetanide as a selective NKCC1 inhibitor either alone or in combination with the phenobarbital in the pilocarpine model of epilepsy. Methods: An animal model of Status Epilepticus (SE) was induced with pilocarpine in Wistar male rats followed by phenobarbital and or bumetanide or saline administration for 45 days after the induction of SE by Intraperitoneal (IP) injection. The rats were monitored, their behavior was recorded, and after 24 hours they were sacrificed to study the expression of NKCC1 and KCC2 using real time PCR. Results: The data showed that the effects of a combination of bumetanide with phenobarbital on frequency rate and duration of seizure attack were more than those of the phenobarbital alone. In addition, in the bumetanide and combined treatment groups, NKCC1 expression decreased significantly, compared with untreated epileptic animals. A delayed decrement in NKCC1/KCC2 expression ratio after bumetanide application was also observed. Conclusion: The combination of bumetanide with phenobarbital increases the inhibition of SE and maximizes the potential of GABA signaling pathway, and can be considered as an effective therapeutic strategy in patients with epilepsy.
Middle East respiratory syndrome coronavirus (MERS-CoV) – Saudi Arabia

1 november 2018 disease outbreak news From 17 September through 15 October 2018, the International Health Regulations (IHR 2005) National Focal Point of Saudi Arabia reported eight additional cases of MERS-CoV infection, including three deaths. Of the eight cases reported, three were hospital contacts from one hospital in Dammam and two were household contacts in Riyadh. Details of these cases can be found in a separate document (see link below).