bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of beef genotypes on animal performance, carcass traits, meat quality, and sensory characteristics in grazing or feedlot-finished steers
Authors: Maciel Isabella C F , Schweihofer J P , Fenton J I , Hodbod J , McKendree M G S , Cassida K , Rowntree J E 
Published: November 2021

Abstract
A 2-yr study was conducted to evaluate the effects of beef genotypes and feeding systems on performance, carcass traits, meat quality, and sensory attributes. A 2×2 factorial experiment was used to randomly allocate 60 steers in year 1 (YR1) and 44 steers in year 2 (YR2). The two beef genotypes evaluated were Red Angus (RA), and RA x Akaushi (AK) crossbreed. The steers were allotted to two finishing feeding systems: grazing, a multi-species forage mixture (GRASS) and feedlot finishing, conventional total mixed ration (GRAIN). All steers were slaughtered on the same day, at 26 and 18 mo of age (GRASS and GRAIN, respectively), and carcass data were collected 48 h postmortem. Growth and slaughter characteristics were significantly impacted by the finishing system (P &lt; 0.01), with the best results presented by GRAIN. Beef genotype affected dressing percent (P &lt; 0.01), ribeye area (P = 0.04), and marbling score (P = 0.01). The AK steers had a tendency (P = 0.09) for lower total gain; however, carcass quality scores were greater compared to RA. There was a genotype by system interaction for USDA yield grade (P &lt; 0.01), where it was lower in GRASS compared to GRAIN in both genotypes, and no difference was observed between the two genotypes for any GRASS or GRAIN systems. There was no difference in meat quality or sensory attributes (P &gt; 0.10) between the two genotypes, except that steaks from AK tended to be juicier than RA (P = 0.06). Thawing loss and color variables were impacted by the finishing system (P &lt; 0.01). L* (lightness) and hue angle presented greater values while a* (redness), b* (yellowness), and chroma presented lower values in GRAIN compared to GRASS. Sensory attributes were scored better in GRAIN than GRASS beef (P &lt; 0.01). There was a genotype by system interaction for flavor (P = 0.02), where beef from RA had a lower flavor rating in GRASS than in GRAIN, and no difference was observed for AK. Within each system, no difference was observed for flavor between RA and AK. Beef from steers in GRASS had greater (P &lt; 0.01) WBSF than those from GRAIN. These results indicate that steers from GRAIN had superior performance and carcass merit and that AK enhanced these traits to a greater degree compared to RA. Furthermore, the beef finishing system had a marked impact on the steaks’ sensory attributes and consumer acceptability. The favorable results for texture and juiciness in GRAIN, which likely impacted overall acceptability, may be related to high marbling.
Association of insulin-like growth factor 1 (IGF1) gene polymorphism with the reproductive performance of three dual-purpose chicken breeds
Authors: Ogunpaimo Olaiwola J , Ojoawo Henry T , Wheto Mathew Y , Adebambo Ayotunde O , Adebambo Olufunmilayo A 
Published: November 2021

Abstract
The study was designed to investigate the association of Insulin-like growth factor 1 (IGF1) gene polymorphism with the reproductive performance of FUNAAB-Alpha, Sasso, and Kuroiler dual-purpose chicken breeds. To achieve this, a total of 250 healthy hens were selected at 12 wk of age and were intensively managed in cages for 52 wk. Blood sample was taken from each chicken at the 34th week and genomic DNA was extracted using Qiagentm DNA extraction kit, PCR was used to amplify the DNA fragments, and the PCR products were electrophoresed. Amplicons obtained were digested with restriction enzyme hinf1, and were further electrophoresed on 1.5% agarose gel. Data obtained were analyzed using the General linear model of SAS (2002) version 9.0 to determine the effect of IGF1 gene polymorphism and the distribution of alleles within the breeds. Results show polymorphism of the IGF1 gene and the restriction analysis indicated two alleles; A 58% and C 42% with the identification of genotypes AA, AC, and CC, and genotypic frequency of 22%, 43%, and 35%, respectively. Significant associations were observed between the polymorphism of the IGF1 gene, age of the bird at first lay, and weight of the hen at first lay. Chickens with haplotype CC came earlier into lay compared to those with the other two haplotypes (AA and AC). Therefore, the study suggests that haplotype CC could be used as a genetic marker to select for an improved laying performance in chickens.
Effect of zinc source and implant strategy on performance, carcass characteristics, and trace mineral concentrations in finishing feedlot steers
Authors: Messersmith Elizabeth M , Hansen Stephanie L 
Published: November 2021

AbstractSeventy-two Angus-crossbred steers (411 ± 16 kg) were assigned to a 2 × 3 factorial arrangement of treatments to examine the effects of blended Zn source supplementation on performance, carcass characteristics, and trace mineral parameters of steers administered no implant or a two-implant program. Factors included implant (IMP) strategies and Zn supplementation. During the 126-d study, steers were either not implanted (NoIMP) or implanted (IS/200; Elanco, Greenfield, IN) on days 0 (Component TE-IS; 80 mg trenbolone acetate + 16 mg estradiol) and 57 (Component TE-200; 200 mg trenbolone acetate + 20 mg estradiol). All steers were fed 70 mg Zn/kg on a dry matter (DM) basis from ZnSO4 + 30 mg Zn/kg DM from either basic ZnCl (Vistore Zn, Phibro Animal Health, Teaneck, NJ), Zn glycinate (Gemstone Zn, Phibro Animal Health), or ZnSO4 (ZnB, ZnG, or ZnS, respectively). Steers were blocked by weight into pens of 6 and fed a dry rolled corn-based diet via GrowSafe bunks (GrowSafe Systems Ltd.; Airdrie, AB, Canada). Data were analyzed using the Mixed Procedure of SAS, with fixed effects of Zn, IMP, and the interaction. Steer was the experimental unit (n = 12 steers/treatment). Liver and muscle collected on days −5, 14, 71, and 120 were analyzed for Zn concentration, and data were analyzed as repeated measures (repeated effect = Day). An IMP × Zn tendency (P = 0.07) was observed for day 126 body weight with no effects of Zn within NoIMP, whereas ZnS tended to be heavier than ZnB with ZnG intermediate within IS/200. Carcass-adjusted overall feed efficiency (G:F) was greatest for ZnS (Zn; P = 0.02). Implanted cattle had greater DM intake, G:F, and carcass-adjusted performance (P ≤ 0.01). Liver Zn concentrations were greater for IS/200 by day 120 (IMP × Day; P = 0.02). Within IS/200, ZnG tended to have greater muscle Zn than ZnS, whereas ZnB was intermediate (Zn × IMP; P = 0.09). No Zn or IMP × Zn (P ≥ 0.12) effects were observed for carcass data. However, IS/200 had greater hot carcass weight, dressing percentage, and ribeye area than NoIMP (P ≤ 0.001). These data suggest that implants improve growth and influence Zn metabolism. Future work should examine Zn sources and supplementation alongside implant strategies.
Screening of 6000 Compounds for Uncoupling Activity: A Comparison Between a Mechanistic Biophysical Model and the Structural Alert Profiler Mitotox
Authors: Ebert Andrea , Goss Kai-Uwe 
Published: November 2021

Abstract
Protonophoric uncoupling of phosphorylation is an important factor when assessing chemicals for their toxicity, and has recently moved into focus in pharmaceutical research with respect to the treatment of diseases such as cancer, diabetes, or obesity. Reliably identifying uncoupling activity is thus a valuable goal. To that end, we screened more than 6000 anionic compounds for in vitro uncoupling activity, using a biophysical model based on ab initio COSMO-RS input parameters with the molecular structure as the only external input. We combined these results with a model for baseline toxicity (narcosis). Our model identified more than 1250 possible uncouplers in the screening dataset, and identified possible new uncoupler classes such as thiophosphoric acids. When tested against 423 known uncouplers and 612 known inactive compounds in the dataset, the model reached a sensitivity of 83% and a specificity of 96%. In a direct comparison, it showed a similar specificity than the structural alert profiler Mitotox (97%), but much higher sensitivity than Mitotox (47%). The biophysical model thus allows for a more accurate screening for uncoupling activity than existing structural alert profilers. We propose to use our model as a complementary tool to screen large datasets for protonophoric uncoupling activity in drug development and toxicity assessment.
Supervision and Care Quality as Perceived by Redeployed Attendings, Fellows, and Residents During a COVID-19 Surge: Lessons for the Future
Authors: Young John Q. , Friedman Karen A. , Thakker Krima , Hennus Marije P. , Hennessy Martina , Patterson Aileen , Yacht Andrew , ten Cate Olle 
Published: November 2021

Purpose
To better prepare for potential future large-scale redeployments, this study examines quality of supervision and care as perceived by redeployed residents, fellows, and attendings during a COVID-19 surge.

Method
During April and May 2020, attendings, fellows, and residents redeployed at 2 teaching hospitals were invited to participate in a survey, which included questions on respondents’ prior experience; redeployed role; amount of supervision needed and received; and perceptions of quality of supervision, patient care, and interprofessional collaboration. Frequencies, means, and P values were calculated to compare perceptions by experience and trainee status. Narrative responses to 2 open-ended questions were independently coded; themes were constructed.

Results
Overall, 152 of 297 (51.2%) individuals responded, including 64 of 142 attendings (45.1%), 40 of 79 fellows (50.6%), and 48 of 76 residents (63.2%). Fellows and attendings, regardless of prior experience, perceived supervision as adequate. In contrast, experienced residents reported receiving more supervision than needed, while inexperienced residents reported receiving less supervision than needed and rated overall supervision as poor. Attendings, fellows, and experienced residents rated the overall quality of care as acceptable to good, whereas inexperienced residents perceived overall quality of care as worse to much worse, particularly when compared with baseline.

Conclusions
Narrative themes indicated that the quality of supervision and care was buffered by strong camaraderie, a culture of informal consultation, team composition (mixing experienced with inexperienced), and clinical decision aids. The markedly negative view of inexperienced residents suggests a higher risk for disillusionment, perhaps even moral injury, during future redeployments. Implications for planning are explored.
Association of paraoxonase 1 activity and insulin resistance models in type 2 diabetes mellitus: Cross-sectional study
Authors: Adiga Usha , Banawalikar Nandit , Menambath Desy Thayyil 
Published: November 2021

Background:
Diabetes mellitus is a metabolic disorder characterized by hyperglycemia due to defects in insulin secretion, insulin action, or both. Chronic hyperglycemia induces reactive oxygen species and increases oxidative stress. Human serum paraoxonase-1 (PON-1) is an enzyme synthesized in the liver, and it is an antioxidant enzyme with a beneficial role in fighting oxidative stress. The objective of the study was to compare PON-1 activity in type 2 diabetes mellitus (T2DM) and nondiabetics, as well as to find the association between PON-1 activity and different insulin resistance (IR) models in diabetics.

Methods:
The cross-sectional study recruited 100 diabetic and 100 age and gender-matched controls. Fasting blood glucose, insulin, and C-peptide, were assayed. PON-1 activity was measured by the spectrophotometric method. Various insulin resistance models based on insulin and C-peptide were constructed using appropriate formulae. Receiver operating characteristic was constructed to find if PON-1 can be a good marker for diabetes.

Results:
PON-1 activity was found to be significantly higher (p < 0.0001) in diabetics compared to controls. Highly significant hyperinsulinemia (p < 0.0001) was noted in diabetics. C-peptide levels were significantly lower in cases (p = 0.0215) as compared to controls. Homeostasis model assessment (HOMA)-IR C was insignificantly higher in cases. HOMA B cell, HOMA 1% B cell, and C-peptide–based IR (CIR) were significantly lower in cases (p < 0.0001 and p = 0.002), respectively, as compared to controls. An odds ratio of 3.15 was obtained, which suggests that the risk of T2DM is 3 times higher in subjects with elevated PON-1 levels. Chi-square showed a significant association (p = 0.0001) between DM and PON-1 levels; the chi-square statistic value (with Yates correction) was 14.49. Correlation data showed that PON-1 activity had a significant negative correlation with quantitative insulin sensitivity check index (r = −0.265, p = 0.019). A significant negative correlation (r = −0.22, p = 0.016) was also seen between PON-1 and CIR (HOMA-IR C). There was no significant correlation seen between PON-1 and other IR models.

Conclusion:
It can be concluded from our study that PON-1 activity is elevated in T2DM patients, which can be a beneficial marker.
Genomic Stratification of Resectable Colorectal Liver Metastasis Patients and Implications for Adjuvant Therapy and Survival
Authors: Ecker Brett L. , Shin Paul , Saadat Lily V. , Court Colin M. , Balachandran Vinod P. , Chandwani Rohit , Drebin Jeffrey A. , Jarnagin William R. , Kingham T. Peter , Soares Kevin C. , Vakiani Efsevia , Wei Alice C. , Kemeny Nancy E. , Smith J. Joshua , Gonen Mithat , D’Angelica Michael I. 
Published: November 2021

Objective:
To determine whether genomic risk groups identified by somatic mutation testing of colorectal liver metastasis (CRLM) can be used for “molecularly-guided” selection for adjuvant systemic chemotherapy and hepatic artery infusion of FUDR (SYS+HAI-FUDR).

Background:
Several genomic biomarkers have been associated with clinical phenotype and survival for patients with resectable CRLM. It is unknown whether prognostication afforded by genomic stratification translates into enhanced patient selection for adjuvant hepatic artery infusion therapy.

Methods:
Consecutive patients with resected CRLM and available mutational characterization via Memorial Sloan Kettering–Integrated Mutation Profiling of Actionable Cancer Targets were reviewed from a prospective institutional database. Patients were stratified into three genomic risk groups based on previously defined alterations in SMAD4, EGFR and the RAS/RAF pathway. The association between SYS+HAI-FUDR and overall survival, relative to adjuvant chemotherapy alone (SYS), was evaluated in each genomic risk group by Cox proportional hazard regression and propensity score matched analyses.

Results:
A total of 334 patients (SYS+HAI-FUDR 204; SYS 130) were identified; the rates of RAS/RAF alterations and SMAD4 inactivation were 47.4% and 11.7%, respectively. After a median follow-up of 58 months, adjuvant SYS+HAI-FUDR was independently associated with a reduced risk of death (HR 0.50, 95%CI 0.26–0.98, P = 0.045) in the low-risk genomic group, but not in the moderate-risk (HR 1.07, 95%CI 0.5–2.07, P = 0.749) or high-risk (HR 1.62, 95%CI 0.29–9.12, P = 0.537) cohorts. Following propensity score matching, adjuvant SYS+HAI-FUDR remained associated with significant improvements in long-term survival selectively in the low-risk genomic cohort (5-year actuarial survival: 89% vs. 68%, P = 0.019).

Conclusions:
Genomic alterations in RAS/RAF, SMAD4, and EGFR may be useful to guide treatment selection in resectable CRLM patients and warrant external validation and integration in future clinical trial design.
Coronary Artery Stent for Securing High-risk Pancreatico-jejunal Anastomosis After Pancreatoduodenectomy
Authors: Huscher Cristiano , Perri Giampaolo , Lazzarin Gianni , Marchegiani Giovanni , Malleo Giuseppe , Salvia Roberto , Bassi Claudio 
Published: November 2021

Objective:
To assess the feasibility and clinical utility of coronary artery stent (CAS) in securing pancreatico-jejunal anastomosis (PJ) and avoid stent displacement after pancreatoduodenectomy (PD).

Summary of Background Data:
Externalized trans-anastomotic stent (ETS) is a standard mitigation strategy for postoperative pancreatic fistula (POPF) in high-risk patients. However, major morbidity remains extremely elevated, especially in case of ETS malfunction due to displacement.

Methods:
A pilot series of 72 patients underwent PD and PJ with CAS positioning between January 2016 and December 2019. All patients were at high-risk for POPF (soft pancreatic texture; main pancreatic duct diameter ≤ 3 mm) and underwent a CT-scan at postoperative day 5 and 10 to assess the correct CAS positioning. Postoperative outcomes were analyzed, and displacement rates were compared with a cohort of 141 patients with the same high-risk characteristics, undergoing PD with PJ and externalized trans-anastomotic stent (ETS).

Results:
No CAS-related complications were registered in the study group. In particular, no CAS displacement was registered, compared to a 28% ETS malfunction (either displacement or occlusion). The POPF rate, major morbidity, and mortality were 11%, 6%, and 0% respectively.

Conclusions:
The CAS positioning appears to be a feasible and safe mitigation strategy to secure PJ anastomosis after PD with high POPF risk avoiding stent displacement. Further validation and comparison with current standard of care is required in a prospective controlled setting.
Initiating early palliative care for older people with advanced cancer and its barriers
Authors: Bugaj Till J. , Oeljeklaus Lydia , Haun Markus W. 
Published: November 2021

Purpose of review
Early palliative care (EPC) is known to generally improve both health-related quality of life (QoL) and symptom intensity at small effect sizes. However, it is unclear whether EPC is effective in older people, a population that is notoriously unaccounted for. This review summarizes the recent evidence concerning the efficacy of EPC in older patients with advanced cancer and delineates existing barriers to accessing respective services.

Recent findings
The search for studies published in MEDLINE from January 2020 to September 2021 yielded six relevant records. Data from a recent feasibility trial and subgroups from larger randomised trials point to a somewhat lesser decline in QoL for patients undergoing EPC compared to those receiving treatment as usual. However, enrolling older patients in such trials remains a major challenge mostly due to them feeling too ill to participate.

Summary
For older patients, the efficacy of EPC, like many other medical interventions, has hardly been studied so far. Existing work yielded several specific barriers for older patients to access this type of care. Future research should prioritize efficacy trials of EPC tailored to the needs of older patients enabling clinicians to enter truly evidence-based shared decision-making with their patients.
Microglia do not restrict SARS-CoV-2 replication following infection of the central nervous system of K18-hACE2 transgenic mice
Authors: Olivarria Gema M. , Cheng Yuting , Furman Susana , Pachow Collin , Hohsfield Lindsay A. , Smith-Geater Charlene , Miramontes Ricardo , Wu Jie , Burns Mara S. , Tsourmas Kate I. , Stocksdale Jennifer , Manlapaz Cynthia , Yong William H. , Teijaro John , Edwards Robert , Green Kim N. , Thompson Leslie M. , Lane Thomas E. 
Published: November 2021

AbstractUnlike SARS-CoV-1 and MERS-CoV, infection with SARS-CoV-2, the viral pathogen responsible for COVID-19, is often associated with neurologic symptoms that range from mild to severe, yet increasing evidence argues the virus does not exhibit extensive neuroinvasive properties. We demonstrate SARS-CoV-2 can infect and replicate in human iPSC-derived neurons and that infection shows limited anti-viral and inflammatory responses but increased activation of EIF2 signaling following infection as determined by RNA sequencing. Intranasal infection of K18 human ACE2 transgenic mice (K18-hACE2) with SARS-CoV-2 resulted in lung pathology associated with viral replication and immune cell infiltration. In addition, ∼50% of infected mice exhibited CNS infection characterized by wide-spread viral replication in neurons accompanied by increased expression of chemokine (Cxcl9, Cxcl10, Ccl2, Ccl5andCcl19) and cytokine (Ifn-λandTnf-α) transcripts associated with microgliosis and a neuroinflammatory response consisting primarily of monocytes/macrophages. Microglia depletion via administration of colony-stimulating factor 1 receptor inhibitor, PLX5622, in SARS-CoV-2 infected mice did not affect survival or viral replication but did result in dampened expression of proinflammatory cytokine/chemokine transcripts and a reduction in monocyte/macrophage infiltration. These results argue that microglia are dispensable in terms of controlling SARS-CoV-2 replication in in the K18-hACE2 model but do contribute to an inflammatory response through expression of pro-inflammatory genes. Collectively, these findings contribute to previous work demonstrating the ability of SARS-CoV-2 to infect neurons as well as emphasizing the potential use of the K18-hACE2 model to study immunological and neuropathological aspects related to SARS-CoV-2-induced neurologic disease.ImportanceUnderstanding the immunological mechanisms contributing to both host defense and disease following viral infection of the CNS is of critical importance given the increasing number of viruses that are capable of infecting and replicating within the nervous system. With this in mind, the present study was undertaken to evaluate the role of microglia in aiding in host defense following experimental infection of the central nervous system (CNS) of K18-hACE2 with SARS-CoV-2, the causative agent of COVID-19. Neurologic symptoms that range in severity are common in COVID-19 patients and understanding immune responses that contribute to restricting neurologic disease can provide important insight into better understanding consequences associated with SARS-CoV-2 infection of the CNS.
NUDT18 catalyzes the hydrolysis of active metabolites of the antivirals Remdesivir, Ribavirin and Molnupiravir
Authors: Jemth Ann-Sofie , Scaletti Emma Rose , Homan Evert , Stenmark Pål , Helleday Thomas , Michel Maurice 
Published: November 2021

AbstractRemdesivir and Molnupiravir have gained considerable interest due to their activity against SARS-CoV-2. Cellular hydrolysis of their active triphosphate forms, Remdesivir-TP and Molnupiravir-TP, would decrease drug efficiency. We therefore tested Remdesivir-TP as a substrate against a panel of human hydrolases and found that NUDT18 catalyzes the hydrolysis of Remdesivir-TP. The kcat value of NUDT18 for Remdesivir-TP was determined to 2.6 s-1 and the Km value was 156 μM, suggesting that NUDT18 catalyzed hydrolysis of Remdesivir-TP occurs in cells. We demonstrate that the triphosphates of the antivirals Ribavirin and Molnupiravir are hydrolyzed by NUDT18, albeit with a lower efficiency compared to Remdesivir-TP. NUDT18 also hydrolyses the triphosphates of Sofosbuvir and Aciclovir although with significantly lower activity. These results suggest that NUDT18 can act as a cellular sanitizer of modified nucleotides and may influence the antiviral efficacy of Remdesivir, Molnupiravir and Ribavirin. NUDT18 is expressed in respiratory epithelial cells and may limit the antiviral efficacy of Remdesivir and Molnupiravir against SARS-CoV2 replication by decreasing the intracellular concentration of their active metabolites at their intended site of action.