Miracle-dz/UniFAR-FTUs huggingface dataset:
E ffect of cytokinins on in vitro multiplication of S ophora tonkinensis

Objective: T o determine the effects of different cytokinins at various concentrations on in vitro shoot multiplication of an important medicinal plant. Methods: N odal explants ( 1 . 5 - 2 . 0 cm ) of Sophora tonkinensis were used. M ultiple shoots were induced from nodal explants cultured on the M urashige and S koog ( MS ) medium supplemented with 0 . 0 , 0 . 5 , 1 . 0 , 2 . 0 , 4 . 0 , 8 . 0 , or 16 . 0 µ mol 2 -isopentyladenine ( 2 i P ) , N 6 benzyladenine, kinetin or thiadiazuron. Results: A mong the four investigated cytokinins, 2 i P showed the best response for shoot multiplication. M aximum shoot induction ( 75 %) was achieved on the MS medium supplemented with 2 . 0 µ mol 2 i P , with a mean number of 5 . 0 shoots per explant. I n comparison to other cytokinins tried, 2 i P showed the highest shoot elongation with a mean shoot length of 4 . 8 cm. R oot initiation was observed within 15 d within the transfer of shoots onto the MS basal medium, and the rooting percentage was 100 % with a mean number of 5 . 4 roots per shoot and root length of 6 . 2 cm over a period of 4 weeks. T he healthy plants, hardened and transferred to a greenhouse for proper acclimatization, exhibited 100 % survival. Conclusions: I t can be summarized that 2 i P is the optimal plant growth regulator for Sophora multiplication.
Tolerance doses for late adverse events after hypofractionated radiotherapy for prostate cancer on trial RTOG 0415

Purpose/Objective: Hypofractionated radiotherapy (HRT) regimens for prostate cancer are emerging, but tolerance doses for late adverse events are scarce. The purpose of this study is to define dose-volume predictors for late gastrointestinal and genitourinary (GI and GU) toxicities after HRT in the multi-center NRG/RTOG 0415 low-risk prostate cancer trial (N=521). Material/methods: Treatment in the studied HRT arm was delivered as 70Gy at 2.5Gy/fraction with 3D-CRT/IMRT (N=108/413). At a median follow-up of 5.9 years, the crude late ≥Grade 2 GI and GU toxicities were 19% and 29%, respectively. For modeling, the complete HRT cohort was randomly split into training and validation (70% and 30%; preserved toxicity rates). Within training, dose-response modeling was based on dose-volume cut-points (EQD2Gy; bladder/ rectum: α / β =6Gy/3Gy), age, acute ≥Grade 2 toxicity, and treatment technique using univariate and multivariate logistic regression on bootstrapping (UVA and MVA). Candidate predictors were determined at p≤0.05, and the selected MVA models were explored on validation where model generalizability was judged if the area under the receiver-operating curve in validation (AUC validation ) was within AUC training ±SD with p≤0.05, and with an Hosmer-Lemeshow p-value (p HL )>0.05. Results: Three candidate predictors were suggested for late GI toxicity: the minimum dose to the hottest 5% rectal volume (D5%[Gy]), the absolute rectal volume <35Gy, and acute GI toxicity (AUC=0.59-0.63; p=0.02-0.04). The two generalizable MVA models, i.e. D5%[Gy] with or without acute GI toxicity (AUC validation =0.64. 0.65; p=0.01, 0.03; p HL =0.45-0.56), suggest that reducing late GI toxicity from 20% to 10% would require reducing D5%[Gy] from ≤65Gy to ≤62Gy (logistic function argument: 17+(0.24D5%[Gy])). Acute GU toxicity showed only a trend to predict late GU toxicity (AUC training =0.57; p=0.07). Conclusion: Uate GI toxicity, following moderate HRT for low-risk prostate cancer, increases with higher doses to small rectal volumes. This work provides quantitative evidence that limiting small rectal dose ‘hotspots’ in clinical practice of such HRT regimens is likely to further reduce the associated rates of GI toxicity.
Expression of Intercellular Adhesion Molecule-1 in Murine Hearts with Acute Myocarditis Caused by Coxsackievirus B3 in cultured murine myocar-1.

essential role the expression of in evaluated the induction of ICAM-1 in myocytes treated with cytokines by immunofluorescence and Northern blot hybridization. Furthermore, we the effects of in vivo administration of anti-ICAM-i mAbs on the associated with myocarditis. We found that CVB3-induced murine acute myocarditis resulted in enhanced expression of ICAM-1 in myocardial cells. The expression of ICAM-1 in myocardial cells could be induced in vitro by IFN-7 and TNF-a, which were shown to be synthesized by the infiltrating cells. In vivo treatment with F(ab')2 fragments of an anti-ICAM-i mAb significantly reduced the myocardial inflammation induced by CVB3. These data strongly suggest that the expression of ICAM-1 in myocardial cells plays a critical role in the cell-mediated cytotoxicity involved in acute viral myocarditis. (J. Clin. Invest. 1993. 91:1327-1336.)
Novel selective positive modulator of calcium-activated potassium channels exerts beneficial effects in a mouse model of spinocerebellar ataxia type 2

Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disorder caused by a polyglutamine expansion within the Ataxin-2 (Atxn2) protein. Purkinje cells (PC) of the cerebellum fire irregularly and eventually die in SCA2. We show here that the type 2 small conductance calcium-activated potassium channel (SK2) play a key role in control of normal PC activity. Using cerebellar slices from transgenic SCA2 mice we demonstrate that SK channel modulators restore regular pacemaker activity of SCA2 PCs. Furthermore, we also show that oral delivery of a novel selective positive modulator of SK2/3 channels (NS13001) alleviates behavioural and neuropathological phenotypes of aging SCA2 transgenic mice. We conclude that SK2 channels constitute a novel target for SCA2 treatment and that the developed selective SK2/3 modulator NS13001 holds promise as a potential therapeutic agent for treatment of SCA2 and possibly other cerebellar ataxias.
Original Article The developmental origins of adult disease

Epidemiological and clinical observations have led to the hypothesis that the risk of developing some chronic diseases in adulthood is inﬂuenced not only by genetic and adult lifestyle factors, but also by environmental factors acting in early life. These factors act through the processes of developmental plasticity and possibly epigenetic modiﬁcation, and can be distinguished from developmental disruption. The concept of predictive adaptation has been developed to explain the relationship between early life events and the risk of later disease. At its base, the model suggests that a mismatch between fetal expectation of its postnatal environment and actual postnatal environment contribute to later adult disease risk. This mismatch is exacerbated, in part, by the phenomenon of ‘maternal constraint’ on fetal growth, which implicitly provides an upper limit of postnatal nutritional environment that humans have adapted for and is now frequently exceeded. These experimental, clinical and conceptual considerations have important implications for prevention and intervention in the current epidemic of childhood obesity and adult metabolic and cardiovascular disorders.
When Language Outgrows Them: Comprehension of Ambiguous Sentences by Children with Normal Hearing or Hearing Loss

Background: In spite of recent gains in language development made by children with hearing loss (HL) as a result of improved auditory prostheses and earlier starts to intervention, these children continue to struggle academically at higher grade levels. We hypothesize that one reason for these incongruent outcomes for language and academics may be that the language demands of school escalate as grade level increases, outstripping the language abilities of children with HL. We tested that hypothesis by examining a higher level skill that is essential for success with academic language, the ability to access multiple interpretations for a sentence. Method: 122 children participated at the end of middle school: 56 with normal hearing (NH), 15 with moderate HL who used hearing aids (HAs), and 51 with severe-to-profound HL who used cochlear implants (CIs). Children’s abilities to provide more than one interpretation for an ambiguous sentence were assessed. These sentences were ambiguous due either to words having multiple meanings or to syntactic structure that could evoke more than one interpretation. Potential predictors of those abilities were evaluated, including expressive vocabulary, comprehension of syntactic structures, grammaticality judgements, forward digit span, and several audiologic factors. Results: Children with NH performed best, children with CIs performed poorest, and children with HAs performed intermediately to those groups. Children in all groups achieved higher scores on the multiple meanings than on the syntactic structure items. The variables that were associated with performance varied across groups. Audiologic factors did not explain any variability in performance on the ambiguous sentences task for children with HL. Conclusions: The kind of linguistic flexibility needed to consider more than one interpretation for sentences lacking immediate, real-world context is essential to processing academic language. Children with HL those with severe-to-profound HL who required CIs – showed deficits in this skill, which could contribute to their ongoing academic struggles. Continued language support is needed for these them to the higher level language skills necessary for through years in school. file of this The copyediting, typesetting, of the production be discovered legal disclaimers
GASTROINTESTINAL, Intestinal Epithelial Chemokine (C-C Motif) Ligand 7 Overexpression Enhances Acetaminophen-Induced Hepatotoxicity in Mice

Acetaminophen (APAP) overdose e induced hepatotoxicity is the leading cause of drug-induced liver injury worldwide. The related injury pathogenesis is mainly focused on the liver. Here, the authors report that gut barrier disruption may also be involved in APAP hepatotoxicity. APAP administration led to gut leakiness and colonic epithelial chemokine (C-C motif) ligand 7 (CCL7) up-regulation. Intestinal epithelial cell (IEC)-speci ﬁ c CCL7 transgenic mice (CCL7 tgIEC mice) showed markedly increased myosin light chain kinase phosphorylation, and elevated gut permeability and bacterial translocation into the liver compared to wild-type mice. Global transcriptome analysis revealed that the expression of hepatic proin ﬂ ammatory genes was enhanced in CCL7 tgIEC mice compared with wild-type animals. Moreover, CCL7 overexpression in intestinal epithelial cells signi ﬁ cantly augmented APAP-induced
Primary hepatic mucosa-associated lymphoid tissue lymphoma: case report and literature review.

BACKGROUND The prevalence of primary hepatic mucosa-associated lymphoid tissue (MALT) lymphomas is extremely low. Here, we describe a case of this disease misdiagnosed as hepatocellular carcinoma (HCC) and review relevant literature to prevent future misdiagnoses. CASE PRESENTATION a 58-year-old woman complained about abdominal pain for more than four months. About two months prior, she came to our hospital with elevated levels of HBV DNA and positive HBsAg and HBcAb. After two months of entecavir treatment, HBV DNA decreased to a normal level. She returned to the hospital with worsened abdominal pain for over a month. Magnetic resonance imaging and systemic positron emission tomography-computed tomography identified two nodes in the liver, and she was diagnosed with HCC. The patient then underwent a laparoscopic hepatectomy. Microscopic examination showed a diffuse infiltrate of small-to-medium-sized lymphocytes and lymphoepithelial lesions. Immunohistochemical staining showed that most of the lymphoid cells were strongly positive for CD20, CD79a, BCL2, IgM and weakly positive for IgD, while negative for CD3, CD10, BCL6, MUM1, CD43, CD5, cyclin D1, CD23, CD30, and PD1. The Ki-67 index of lymphoid cells was 5%. Further pathologic analysis confirmed the diagnosis of primary hepatic MALT lymphoma. The patient received antiviral treatment and recovered well with no sign of relapse for 17 months. CONCLUSIONS Primary hepatic MALT lymphoma is an uncommon disease that is difficult to diagnose and has no widely accepted treatment. Surgical resection is a good choice for both diagnosis and local therapy, and strict follow-up of the patient is essential.
Retargeting Interleukin-2 Signaling to NKG2D-Expressing Tumor Infiltrating Leukocytes Improves Adoptive Transfer Immunotherapy

Ex vivo expansion followed by reinfusion of tumor infiltrating leucocytes (TILs) has been utilized successfully for the treatment of multiple malignancies. Most protocols rely on the use of the cytokine interleukin-2 (IL-2) to expand TILs prior to reinfusion. In addition, TIL administration relies on systemic administration of IL-2 post-reinfusion to support transferred cell survival. The use of IL-2, however, can be problematic due to its preferential expansion of regulatory T and myeloid cells as well as its systemic side effects. Here we describe the use of a novel IL-2 mutant retargeted to NKG2D rather than the high affinity IL-2 receptor for TIL-mediated immunotherapy in a murine model of malignant melanoma. We demonstrate that the NKG2D-retargeted IL-2 (called OMCPmutIL-2) preferentially expands TIL-resident cytotoxic lymphocytes, such as CD8 + T cells, NK cells, and γδ T cells while wild-type IL-2 provides a growth advantage for CD4 + Foxp3 + T cells as well as myeloid cells. OMCPmutIL-2 expanded cytotoxic lymphocytes express higher levels of tumor homing receptors such as LFA-1, CD49a and CXCR3 which correlate with TIL localization to the tumor bed after intravenous injection. Consistent with this OMCPmutIL-2 expanded TILs provided superior tumor control compared to those expanded in wild-type IL-2. Our data demonstrate that adoptive transfer immunotherapy can be improved by rational retargeting of cytokine signaling to NKG2D expressing cytotoxic lymphocytes rather than indiscriminate expansion of all TILs.
Evaluation of Genetic Predisposition for MYCN -Amplified Neuroblastoma

To investigate genetic predispositions for MYCN -ampliﬁed neuroblastoma, we performed a meta-analysis of three ge-nome-wide association studies totaling 615 MYCN -ampliﬁed high-risk neuroblastoma cases and 1869 MYCN -nonampliﬁed non-high-risk neuroblastoma cases as controls using a ﬁxed-effects model with inverse variance weighting. All statistical tests were two-sided. We identiﬁed a novel locus at 3p21.31 indexed by the single nucleotide polymorphism (SNP) rs80059929 (odds ratio [OR] ¼ 2.95, 95% conﬁdence interval [CI] ¼ 2.17 to 4.02, P meta ¼ 6.47 (cid:2) 10 -12 ) associated with MYCN ampliﬁed neuroblastoma, which was replicated in 127 MYCN -ampliﬁed cases and 254 non-high-risk controls (OR ¼ 2.30, 95% CI ¼ 1.12 to 4.69, P replication ¼ .02). To conﬁrm this signal is exclusive to MYCN -ampliﬁed tumors, we performed a second meta-analysis comparing 728 MYCN -nonampliﬁed high-risk patients to identical controls. rs80059929 was not statistically signiﬁcant in MYCN -nonampliﬁed high-risk patients (OR ¼ 1.24, 95% CI ¼ 0.90 to 1.71, P meta ¼ .19). SNP rs80059929 is within intron 16 in the KIF15 gene. Additionally, the previously reported LMO1 neuroblastoma risk locus was statistically signiﬁcant only in patients with MYCN- nonampliﬁed high-risk tumors (OR ¼ 0.63, 95% CI ¼ 0.53 to 0.75, P meta ¼ 1.51 (cid:2) 10 -8 ; P meta ¼ . 95). Our results indicate that common genetic variation predisposes to different neuroblastoma genotypes, includ-ing the likelihood of somatic MYCN -ampliﬁcation.
Balance between maternal antiviral response and placental transfer of protection in gestational SARS-CoV-2 infection

Maternal immune responses during pregnancy protect the growing fetus by clearing infection, preventing its vertical transmission, and through transplacental transfer of protective immune mediators to the fetus. How maternal immune response balances SARS-CoV-2 antiviral responses with transplacental transfer of protection to the fetus remains unclear. Our study shows that upon SARS-CoV-2 maternal infection, neutralizing antibodies (NAbs) are infrequently detected in cord blood. We uncovered that this is due to impaired IgG-NAbs placental transfer in symptomatic infection and to the predominance of maternal SARS-CoV-2 NAbs of the IgA and IgM isotypes, which are prevented from crossing the placenta. Crucially, the decision between favoring maternal antiviral response or transplacental transfer of immune protection to the fetus appears to hinge on the balance between IL-6 and IL-10 induced by SARS-CoV-2 infection, decreasing or increasing transplacental transfer of IgG-NAbs, respectively. In addition, IL-10 inversely correlates with maternal NK cell frequency. Finally, we found that ongoing infection favored perinatal transfer of maternal NK cells, highlighting a maternal sponsored mechanism to protect the newborn from horizontal transmission of infection. Our data point to an evolutionary trade-off which at once optimizes maternal viral clearance and vertical transfer of immune protection during the more susceptible perinatal period.
Protein carbamylation and chronic kidney disease progression in the Chronic Renal Insufficiency Cohort Study

Background. Protein carbamylation is a post-translational protein modification caused, in part, by exposure to urea’s dissociation product cyanate. Carbamylation is linked to cardiovascular outcomes and mortality in dialysis-dependent end-stage kidney disease (ESKD), but its effects in earlier pre-dialysis stages of chronic kidney disease (CKD) are not established. Methods. We conducted two nested case–control studies within the Chronic Renal Insufficiency Cohort Study. First, we matched 75 cases demonstrating CKD progression [50% estimated glomerular filtration rate (eGFR) reduction or reaching ESKD] to 75 controls (matched on baseline eGFR, 24-h proteinuria, age, sex and race). In the second study, we similarly matched 75 subjects who died during follow-up (cases) to 75 surviving controls. Baseline carbamylated albumin levels (C-Alb, a validated carbamylation assay) were compared between cases and controls in each study. Results. At baseline, in the CKD progression study, other than blood urea nitrogen (BUN) and smoking status, there were no significant differences in any matched or other pa-rameter. In the mortality group, the only baseline difference was smoking status. Adjusting for baseline differences, the top tertile of C-Alb was associated with an increased risk of CKD progression [odds ratio (OR) ¼ 7.9; 95% confidence interval (CI) 1.9–32.8; P ¼ 0.004] and mortality (OR ¼ 3.4; 0.05) when compared with the bottom tertile. C-Alb correlated with eGFR but was more strongly correlated with BUN. Conclusions. Our data suggest that protein carbamylation is a predictor of CKD progression, beyond traditional risks including eGFR and proteinuria. Carbamylation’s association with mortality was smaller in this limited sample size.
Role of Dipicolinic Acid in Resistance and Stability of Spores of Bacillus subtilis with or without DNA-Protective (cid:2) / (cid:3) -Type Small Acid-Soluble Proteins

Dipicolinic acid (DPA) comprises (cid:4) 10% of the dry weight of spores of Bacillus species. Although DPA has long been implicated in spore resistance to wet heat and spore stability, deﬁnitive evidence on the role of this abundant molecule in spore properties has generally been lacking. Bacillus subtilis strain FB122 ( sleB spoVF ) produced very stable spores that lacked DPA, and sporulation of this strain with DPA yielded spores with nearly normal DPA levels. DPA-replete and DPA-less FB122 spores had similar levels of the DNA protective (cid:1) / (cid:2) -type small acid-soluble spore proteins (SASP), but the DPA-less spores lacked SASP- (cid:3) . The DPA-less FB122 spores exhibited similar UV resistance to the DPA-replete spores but had lower resistance to wet heat, dry heat, hydrogen peroxide, and desiccation. Neither wet heat nor hydrogen peroxide killed the DPA-less spores by DNA damage, but desiccation did. The inability to synthesize both DPA and most (cid:1) / (cid:2) -type SASP in strain PS3664 ( sspA sspB sleB spoVF ) resulted in spores that lost viability during sporulation, at least in part due to DNA damage. DPA-less PS3664 spores were more sensitive to wet heat than either DPA-less FB122 spores or DPA-replete PS3664 spores, and the latter also retained viability during sporulation. These and previous results indicate that, in addition to (cid:1) / (cid:2) -type SASP, DPA also is extremely important in spore resistance and stability and, further, that DPA has some speciﬁc role(s) in protecting spore DNA from damage. Speciﬁc roles for DPA in protecting spore DNA against damage may well have been a major driving force for the spore’s accumulation of the high levels of this small molecule.
Exploring publicly reported inpatient psychiatric facility care coordination measures and 30-day “All-Cause Unplanned Readmission after Psychiatric Hospitalization” rates

Objective: The Medicare Inpatient Psychiatric Facility Quality Reporting (IPFQR) program has required inpatient psychiatric facilities to collect and publicly report a suite of quality measures since late 2012. This study aimed to explore the association between facility-level 30-day risk-adjusted all-cause readmission (medical or psychiatric) after psychiatric hospitalization (READM-30-IPF) outcome measure and care coordination process measures in the IPFQR. Methods: This study used psychiatric facility-level performance data from the IPFQR that is publicly reported on the Hospital Compare website and reflects facility performance from July 2015 to June 2017. This study used a cross-sectional design and linear regression models controlling for hospital and community characteristics and state fixed-effects. Results: The mean facility-level 30-day readmission rate was 20% (SD=2%) with substantial variation by facility type, ownership status, rurality, and percent of minority county residents. Regression results showed that facilities with top tercile performance on the 7-day mental health follow-up (FUH-7) measure had readmission rates that were significantly lower than facilities in bottom tercile (Coef=−0.58, p<0.01), although the magnitude of this difference was small. The readmission measure, however, did not vary by facilities’ performance on discharge plan creation and transmission measures. Conclusions: Results suggested that facilities have substantial opportunities to reduce readmissions after psychiatric hospitalization. The association between hospital performance on care coordination process measures and the all-cause readmission measure currently included in the IPFQR is minimal. The IPFQR should evaluate whether the measures included in the program are adequately capturing compliance with evidence-based processes and desired outcomes.
Structure and Flexibility of Project Teams under Turbulent Environments: An Application of Agent-Based Simulation

The extent of authority and autonomy granted to the project manager and to individual team members has a significant impact on the ability of the project team to meet stakeholders’ goals and expectations. This is particularly true in dynamic environments, where resources, requirements, and other conditions change rapidly, and a great deal of innovation is required. In this paper, we provide some recommendations regarding the structure and flexibility of project teams operating in turbulent environments. The recommendations are based on a set of experiments carried out with agent-based simulation, a novel tool for organizational design. The observed results show that under high uncertainty, loose designs for project teams outperform tight organizational structures.