Miracle-dz/UniFAR-FTUs huggingface dataset:
Establishment and Characterization of Pemetrexed-Resistant NCI-H460/PMT Cells.

BACKGROUND Pemetrexed (PMT) is a multitargeted antifolate agent that is used for treating patients with non-small cell lung cancer (NSCLC). However, patients have presented clinical responses of drug resistance to PMT. OBJECTIVE This study aimed to explore the underlying mechanisms of PMT resistance in NSCLC cells. METHODS PMT-resistant NCI-H460/PMT cells were established by treating with PMT in a dosage-escalation manner. MTT assay and colony formation were performed to detect the cell proliferation. Immunofluorescence was used to detect the expression of Ki-67. Transwell assay was performed to measure cell migration ability. qPCR and Western blot were used to detect the mRNA and protein expression levels of indicated genes. Small interfering RNAs (siRNA) were used to knockdown ABCB1 and Thymidylate Synthase (TYMS). RESULTS This study showed that compared with the parental cells, the NCI-H460/PMT cells displayed weakened proliferation and enhanced cell mobility. In addition, the NCI-H460/PMT cells demonstrated cellular senescence, which might result in PMT resistance. The NCI-H460/PMT cells exhibited cross-resistance to other chemotherapeutics, including fluorouracil, paclitaxel, doxorubicin, etoposide and gemcitabine, possibly because of the upregulated expression of ABCB1. However, the ABCB1 knockdown by siRNA failed to eradicate PMT resistance. Moreover, TYMS, a target of PMT, was obviously upregulated in the resistant cells. The genetic silence of TYMS partially abrogated PMT resistance, suggesting that the overexpression of TYMS was a key resistant mechanism of PMT. CONCLUSION The overexpression of TYMS was an important resistance mechanism of PMT for KRAS-mutated NCI-H460 cells. Cross-resistance to other chemotherapeutics should be considered in addressing PMT resistance.
The hydraulic efficiency–safety trade‐off differs between lianas and trees

Abstract Hydraulic traits are important for woody plant functioning and distribution. Associations among hydraulic traits, other leaf and stem traits, and species’ performance are relatively well understood for trees, but remain poorly studied for lianas. We evaluated the coordination among hydraulic efficiency (i.e., maximum hydraulic conductivity), hydraulic safety (i.e., cavitation resistance), a suite of eight morphological and physiological traits, and species’ abundances for saplings of 24 liana species and 27 tree species in wet tropical forests in Panama. Trees showed a strong trade‐off between hydraulic efficiency and hydraulic safety, whereas efficiency and safety were decoupled in lianas. Hydraulic efficiency was strongly and similarly correlated with acquisitive traits for lianas and trees (e.g., positively with gas exchange rates and negatively with wood density). Hydraulic safety, however, showed no correlations with other traits in lianas, but with several in trees (e.g., positively with leaf dry matter content and wood density and negatively with gas exchange rates), indicating that in lianas hydraulic efficiency is an anchor trait because it is correlated with many other traits, while in trees both efficiency and safety are anchor traits. Traits related to shade tolerance (e.g., low specific leaf area and high wood density) were associated with high local tree sapling abundance, but not with liana abundance. Our results suggest that different, yet unknown mechanisms determine hydraulic safety and local‐scale abundance for lianas compared to trees. For trees, the trade‐off between efficiency and safety will provide less possibilities for ecological strategies. For lianas, however, the uncoupling of efficiency and safety could allow them to have high hydraulic efficiency, and hence high growth rates, without compromising resistance to cavitation under drought, thus allowing them to thrive and outperform trees under drier conditions.
Physical, Chemical and Palatability Traits of Electrically Stimulated, Hot-boned, Vacuum-packaged Beef.

The right sides of six beef carcasses were electrically stimulated, whereas the left sides were not so treated. Sections of longissimus and semimembranosus muscles were removed from electrically stimulated sides at 1 h postmortem (hot-boned) and from sides which were not electrically stimulated at 24 h postmortem (conventionally boned); these muscles were vacuum-packaged immediately after removal and aged for 2 weeks at 1 ± 1 C. After aging, steaks were removed and used for determinations of palatability, cooking loss, pH, sarcomere length and protein solubility. Further evaluation included purification and electrophoresis of myofibrillar proteins. Longissimus muscles from electrically stimulated, hot-boned beef had lower (P < .05) juiciness ratings than those from conventionally handled sides; semimembranosus muscles from electrically stimulated, hot-boned sides sustained lower (P < .05) weight losses during storage but higher (P < .05) cooking losses than muscles from conventionally handled sides. Hot-boning of electrically stimulated beef had no effect (P > .05) on tenderness, flavor desirability, pH, sarcomere length, amount of non-protein nitrogen or percentage of soluble myofibrillar proteins; slight alterations were noted in the electrophoretic banding patterns, on SDS gels, of myofibrillar proteins from electrically stimulated. hot-boned sides. Hot-boned beef was as palatable as conventionally handled beef if sides were electrically stimulated on the kill floor before hot-boning and if beef from both treatments was vacuum packaged and aged for 2 weeks at 1 ± 1 C.
Child maltreatment, adaptive functioning, and polygenic risk: A structural equation mixture model

Abstract This study used a structural equation mixture model to examine associations between child maltreatment, polygenic risk, and indices of adaptive functioning. Children aged 6 to 13 years (N = 1,004), half maltreated, half nonmaltreated, were recruited to attend a research day camp. Multi-informant indicators of prosocial behavior, antisocial behavior, withdrawn behavior, and depression were collected and used in a latent class analysis. Four classes emerged, characterizing “well-adjusted,” “externalizing,” “internalizing,” and “socially dominant” groups. Twelve genetic variants, previously reported in the Gene × Environment literature, were modeled as one weighted polygenic risk score. Large main effects between maltreatment and adaptive functioning were observed (Wald = 35.3, df = 3, p < .0001), along with evidence of a small Gene × Environment effect (Wald = 13.5, df = 3, p = .004), adjusting for sex, age, and covariate interaction effects.
Optimal Protein Intake during Weight Loss Interventions in Older Adults with Obesity

Abstract Obesity rates in people 60 years and older are increasing. While obesity is linked with detrimental health risks, weight loss in this population has previously been considered controversial due to potential worsening of age-related sarcopenia. Protein intake during energy restriction has been linked to lean body mass preservation. No formal guidelines for optimal protein intake during structured weight loss interventions exist for this population, but it appears that the current Recommended Dietary Allowance of 0.8 grams per kilogram of body weight per day may be inadequate. The purpose of this review is to discuss optimal protein intake during structured weight loss interventions in persons 60 years and older with obesity and to present a framework for guidelines to be used by health professionals focusing on weight loss interventions in older adults. Goals for the amount, source, and timing of protein intake, from both food and supplements, are presented and discussed.
Trends in incidence of methicillin-resistant Staphylococcus aureus bloodstream infections differ by strain type and healthcare exposure, United States, 2005-2013.

BACKGROUND Previous reports suggested that U.S. methicillin-resistant Staphylococcus aureus (MRSA) strain epidemiology has changed since the rise of USA300 MRSA. We describe invasive MRSA trends by strain type. METHODS Data came from five CDC Emerging Infections Program sites conducting population-based surveillance and collecting isolates for invasive MRSA (i.e., from normally sterile body sites), 2005-2013. MRSA bloodstream infection (BSI) incidence/100,000 population was stratified by strain type and epidemiologic classification of healthcare exposures. Invasive USA100 vs USA300 case characteristics from 2013 were compared through logistic regression. RESULTS From 2005-2013, USA100 incidence decreased most notably for hospital-onset (6.1 vs 0.9 / 100,000 persons, P<0.0001) and healthcare-associated, community-onset (10.7 vs 4.9 / 100,000 persons, P<0.0001) BSIs. USA300 incidence for hospital-onset BSIs also decreased (1.5 vs 0.6 / 100,000 persons, P<0.0001). However, USA300 incidence did not significantly change for healthcare-associated, community-onset (3.9 vs 3.3 / 100,000 persons, P=0.05) or community-associated BSIs (2.5 vs 2.4 / 100,000 persons, P=0.19). Invasive MRSA was less likely to be USA300 in patients who were older (adjusted odds ratio [aOR] 0.97 per year, 95% confidence interval [CI] 0.96-0.98), previously hospitalized (aOR 0.36, 95% CI 0.24-0.54), or had central lines (aOR 0.44, 95% CI 0.27-0.74) and associated with USA300 in people who inject drugs (aOR 4.58, 95% CI 1.16-17.95). CONCLUSIONS Most of the decline in MRSA BSIs was from decreases in USA100 BSI incidence. Prevention of USA300 MRSA BSIs in the community will be needed to further reduce burden from MRSA BSIs.
Effects of dietary CP and amino acid restriction on the growth dynamics of organs and body components in entire male, castrated and female pigs

The optimized use of dietary nutrients and the accurate knowledge of the growth dynamics of body components is important for efficient pig production. This study aimed at evaluating the growth of carcass components and organs of Swiss Large White pigs from birth to 140 kg BW depending on the CP and amino acid (AA) supply. A total of 66 entire males (EM), 58 castrates (CA) and 66 female (FE) pigs were used. From 20 kg BW onwards, they had either ad libitum access to a control (C) or a diet (LP) with 20% lower CP, lysine, methionine + cystine, threonine and tryptophan content compared to C. The weight of organs, primal cuts and external fat were recorded in eight EM and eight FE; at 10 kg BW, on two EM, CA and FE each, and at 20 kg BW, on eight pigs from each sex. From 40 to 140 kg BW at 20 kg intervals, measurements were recorded on four pigs per sex and dietary treatment. The weight of each component was related to empty body (EB) using allometric regressions. Kidneys were heavier (P<0.05) in C- than LP-pigs and in EM than CA and FE. Above 21 kg EB weight, growth rate of LP-FE overpassed (P<0.05) the one of C-pigs. Consequently, LP-FE had heavier (P<0.05) lean cuts than C-pigs in the finisher period. However, LP-CA and LP-EM displayed lower (P<0.05) weights and growth rates of the lean cuts than C-CA and C-EM. Shoulder and loin weights and growth rates were reduced (P<0.05) in LP-pigs when compared to C-pigs. Growth rates of the ham were greater (P<0.05) in LP-FE than C-FE, whereas in LP-EM and LP-CA they were lower (P<0.05) than their C-counterparts. Total amounts of subcutaneous fat, backfat, ham fat and shoulder fat were lower (P<0.05) in C- than LP-pigs. The total amount of subcutaneous fat, backfat and shoulder fat of C-CA was, regardless of diet, greater (P<0.05) than of C-FE. In the LP group, this difference was even more pronounced. The amount of deposited ham fat was greater (P<0.05) in LP-CA than LP-FE, but not in C-CA v. C-FE. Differences in kidney weights suggested a greater nitrogen clearance required in C-pigs. Overall, dietary restriction and sex did not affect all body parts to the same extent. This study further suggests the possibility to reduce the CP and AA supply in FE without compromising the yield of primal lean cuts or increasing the amount of subcutaneous fat.
Quality of Life with Late‐Stage Dementia: Exploring Opportunities to Intervene

In late‐stage dementia, families often prioritize quality of life (QoL) and comfort, yet little research examines factors impacting QoL. We sought to (1) describe temporal trends in QoL in late‐stage dementia, and (2) explore associations between patient characteristics, care interventions, and QoL.
Melatonin Mediates Enhancement of Stress Tolerance in Plants

Melatonin is a multifunctional signaling molecule, ubiquitously distributed in different parts of plants and responsible for stimulating several physiological responses to adverse environmental conditions. In the current review, we showed that the biosynthesis of melatonin occurred in plants by themselves, and accumulation of melatonin fluctuated sharply by modulating its biosynthesis and metabolic pathways under stress conditions. Melatonin, with its precursors and derivatives, acted as a powerful growth regulator, bio-stimulator, and antioxidant, which delayed leaf senescence, lessened photosynthesis inhibition, and improved redox homeostasis and the antioxidant system through a direct scavenging of reactive oxygen species (ROS) and reactive nitrogen species (RNS) under abiotic and biotic stress conditions. In addition, exogenous melatonin boosted the growth, photosynthetic, and antioxidant activities in plants, confirming their tolerances against drought, unfavorable temperatures, salinity, heavy metals, acid rain, and pathogens. However, future research, together with recent advancements, would support emerging new approaches to adopt strategies in overcoming the effect of hazardous environments on crops and may have potential implications in expanding crop cultivation against harsh conditions. Thus, farming communities and consumers will benefit from elucidating food safety concerns.
Colistin Sulfate Chiral Stationary Phase for the Enantioselective Separation of Pharmaceuticals Using Organic Polymer Monolithic Capillary Chromatography †

A new functionalized polymer monolithic capillary with a macrocyclic antibiotic, namely colistin sulfate, as chiral selector was prepared via the copolymerization of binary monomer mixtures consisting of glycidyl methacrylate (GMA) and ethylene glycol dimethacrylate (EGDMA) in porogenic solvents namely 1-propanol and 1,4-butanediol, in the presence of azobisiso-butyronitrile (AIBN) as initiator and colistin sulfate. The prepared capillaries were investigated for the enantioselective nano-LC separation of a group of racemic pharmaceuticals, namely, α- and β-blockers, anti-inflammatory drugs, antifungal drugs, norepinephrine-dopamine reuptake inhibitors, catecholamines, sedative hypnotics, antihistaminics, anticancer drugs, and antiarrhythmic drugs. Acceptable separation was achieved for many drugs using reversed phase chromatographic conditions with no separation achieved under normal phase conditions. Colistin sulfate appears to be useful addition to the available macrocyclic antibiotic chiral phases used in liquid chromatography.
Hypoxia and Hypoxia-Inducible Factors in Kidney Injury and Repair

Acute kidney injury (AKI) is a major kidney disease characterized by an abrupt loss of renal function. Accumulating evidence indicates that incomplete or maladaptive repair after AKI can result in kidney fibrosis and the development and progression of chronic kidney disease (CKD). Hypoxia, a condition of insufficient supply of oxygen to cells and tissues, occurs in both acute and chronic kidney diseases under a variety of clinical and experimental conditions. Hypoxia-inducible factors (HIFs) are the “master” transcription factors responsible for gene expression in hypoxia. Recent researches demonstrate that HIFs play an important role in kidney injury and repair by regulating HIF target genes, including microRNAs. However, there are controversies regarding the pathological roles of HIFs in kidney injury and repair. In this review, we describe the regulation, expression, and functions of HIFs, and their target genes and related functions. We also discuss the involvement of HIFs in AKI and kidney repair, presenting HIFs as effective therapeutic targets.
The Neurospora crassa Standard Oak Ridge Background Exhibits Atypically Efficient Meiotic Silencing by Unpaired DNA

Meiotic silencing by unpaired DNA (MSUD), an RNAi-mediated gene silencing process, is efficient in crosses made in the Neurospora crassa standard Oak Ridge (OR) genetic background. However, MSUD was decidedly less efficient when the OR-derived MSUD testers were crossed with many wild-isolated strains (W), suggesting that either sequence heterozygosity in tester x W crosses suppresses MSUD, or that OR represents the MSUD-conducive extreme in the range of genetic variation in MSUD efficiency. Our results support the latter model. MSUD was less efficient in near-isogenic crosses made in the novel N. crassa B/S1 genetic background, and in N. tetrasperma strain 85. Possibly, in B/S1 and 85, additional regulatory cues, absent from OR, calibrate the MSUD response. A locus in distal chromosome 1R appears to underlie the OR vs. B/S1 difference. Repeat-induced point mutation (RIP) destroys duplicated genes by G:C to A:T mutation of duplicated DNA sequences. Chromosome segment duplications (Dps) dominantly suppress RIP, possibly by titrating out the RIP machinery. In Dp x N crosses, the Dp–borne genes cannot pair properly, hence efficient MSUD, as in OR, silences them and renders the crosses barren. We speculate that the increased productivity engendered by inefficient MSUD enables small duplications to escape RIP.
Envisioning Future Directions: Conversations With Leaders in Domestic and Sexual Assault Advocacy, Policy, Service, and Research

This article delves into the views of 72 leaders in domestic violence and sexual assault advocacy, policy, service, and research to determine their vision for the future direction of the field. Through discussions with experts, we identified numerous strategies necessary to best meet the needs of domestic violence and sexual assault victims. Common themes focused on the need to (a) examine the context of victims’ and offenders’ experiences; (b) increase cultural competence to adequately provide appropriate victim services and criminal justice responses for underserved, marginalized, and culturally specific populations; (c) increase reliance on victims’ voices; (d) continue to develop partnerships at both the community and the state levels and ensure the role of local communities; (e) expand the concept of successful outcomes that can be reliably and validly assessed; (f) emphasize mixed-methods approaches to address these questions, in recognition that various methods complement each other; and (g) be open to novel or emerging approaches to intervention.
Vedolizumab-mediated integrin α4β7 blockade does not control HIV-1SF162 rebound after cART interruption in humanized mice.

OBJECTIVE The combined cART and anti-α4β7 RM-Act-1 antibody therapy allows macaques to durably control SIV rebound after withdrawal of the interventions. Here, we aimed to investigate whether vedolizumab (VDZ), a clinical-grade humanized anti-α4β7 antibody, would have similar effects in controlling live HIV-1 infection in humanized mice. DESIGN AND METHODS The integrin α4β7 blockade by VDZ was evaluated on human primary memory CD4 T cells and retinoic acid (RA)-induced gut-homing α4β7 memory CD4 T cells (α4β7MEMT) in vitro. The antiretroviral activity of VDZ was determined using pseudotyped R5-tropic HIV-1SF162, which displays binding activity to α4β7. The preventive and immunotherapeutic efficacies of VDZ were further investigated in humanized mice using the live HIV-1SF162 strain compared with RM-Act-1. RESULTS VDZ effectively and dose-dependently blocked the binding of MAdCAM-1, the native ligand of α4β7, to α4β7MEMT cells. HIV-1SF162 not only displayed binding capacity to α4β7-expressing cells, but also showed an increased infectivity in RA-induced α4β7MEMT cells pre-treated with VDZ. Moreover, VDZ failed to prevent live HIV-1SF162 infection and did not reduce the peak viral load when administrated prior to viral challenge in humanized mice. Lastly, in immunotherapeutic settings, the withdrawal of combined cART with either VDZ or RM-Act-1 resulted in an uncontrolled HIV-1SF162 rebound in humanized mice while the α4β7 molecules remained significantly blocked on circulating CD4 T cells. CONCLUSION VDZ neither prevents nor controls HIV-1SF162 infection both in vitro and in humanized mice. Our findings have significant implications to the clinical application of VDZ in HIV-1 preventive and immunotherapeutic interventions.
Empathy and cultural competence in clinical nurses: A structural equation modelling approach

Background: Forgiveness has the potential to resolve painful feelings arising from nurse–patient conflicts. It would be useful to evaluate direct and indirect important factors which are related to forgiveness in order to design interventions that try to facilitate forgiveness. Aim/objective: The purpose of this study was to evaluate the intermediating role of empathy in the cultural competence–forgiveness association among nurses using structural equation modeling. Research design: The research applied a cross-sectional correlational design. Participants and research context: The study included 380 nurses eight hospitals in southern Iran. Ethical considerations: The Ethics and Research Committee of Birjand University of Medical Sciences approved the study protocol. The voluntary nature of participation was explained consent was obtained from participants, and anonymity was guaranteed. Findings: Most of the participants were married and female and fell in the 20- to 30-year-old category. Most of them (89.5%) had a working experience of 1–10 years. The proposed model showed that nurses’ empathy intermediated the association between nurses’ cultural competence and forgiveness which has fitted the data acceptably (root mean square error approximation = 0.070; comparative fit index = 0.993; goodness-of-fit index = 0.983; and χ2/df = 2.85). Conclusion: Empathy skills and cultural competence training were essential for interventions aimed at increasing the tendency to forgive patients. In such interventions, planners should aim at increasing nurses’ cultural competence in order to enhance their empathy toward patients, which can, in turn, lead to a greater wish to forgive patients.
Endoscopic repair of cerebrospinal fluid leaks in the lateral sphenoid sinus recess.

OBJECT Cerebrospinal fluid leaks may occur as a result of trauma or following surgery, and occasionally may also be spontaneous. Leakage of CSF from the lateral sphenoid recess is rare and challenging to treat. The authors present their experience with repairs of 10 CSF leaks that were confined to the lateral sphenoid recess and were treated at the Singapore General Hospital. METHODS A retrospective chart review was conducted for all patients who underwent operations for lateral sphenoid recess CSF leaks between 2001 and 2008. RESULTS Ten repairs were performed in 8 patients by using a transpterygoid approach, with a 90% success rate. In 3 cases the transcranial approach had failed prior to endoscopic repair. "Sandwich reconstruction" under direct vision was performed in all cases, and was completed using cartilage or bone as a rigid support. CONCLUSIONS This series demonstrates that CSF leakage can be managed safely and effectively by using an endoscopic transpterygoid approach in patients in whom both external and endoscopic attempts have failed. The transpterygoid approach used in all of the cases in this series provides wide exposure around the skull base defect, which is crucial for successful repair.