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There is limited data regarding the impact of body mass index (BMI) on outcomes in advanced breast cancer (BC), especially in patients treated with endocrine therapy (ET) + CDK 4/6 inhibitors.

Pooled analysis of individual patient-level data from MONARCH 2 and 3 trials. Patients were classified according to baseline BMI into underweight (<18.5 kg/m2), normal (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2) and obese (≥30 kg/m2) and divided into two treatment groups abemaciclib + ET vs. placebo + ET. Primary endpoint was progression-free survival (PFS) according to BMI in each treatment group. Secondary endpoints were response rate (RR), adverse events (AEs) according to BMI, and loss of weight (≥5% from baseline) during treatment.

This analysis included 1,138 patients (757 received abemaciclib + ET and 381 placebo+ET). There was no difference in PFS between BMI categories in either groups, although normal weight patients presented a numerically higher benefit with abemaciclib + ET (interaction test p=.0 in patients under CDK 4/6 inhibitors may further clarify this hypothesis.The coronavirus disease 2019 (COVID-19) pandemic has created many challenges for pediatric solid organ transplant (SOT) recipients and their families. As the pandemic persists, patients and their families struggle to identify the best and safest practices for resuming activities as areas reopen. Notably, decisions about returning to school remain difficult. We assembled a team of pediatric infectious diseases (ID), transplant ID, public health, transplant psychology, and infection prevention and control specialists to address the primary concerns about school reentry for pediatric SOT recipients in the United States. Based on available literature and guidance from national organizations, we generated consensus statements pertaining to school reentry specific to pediatric SOT recipients. Although data are limited and the COVID-19 pandemic is highly dynamic, our goal was to create a framework from which providers and caregivers can identify the most important considerations for each pediatric SOT recipient to promote a safe return to school.Severe acute respiratory syndrome-coronavirus 2 (SARS-Cov-2) has caused over 13,000,000 cases of coronavirus disease (COVID-19) with a significant fatality rate. Laboratory mice have been the stalwart of therapeutic and vaccine development; however, they do not support infection by SARS-CoV-2 due to the virus's inability to use the mouse orthologue of its human entry receptor angiotensin-converting enzyme 2 (hACE2). While hACE2 transgenic mice support infection and pathogenesis, these mice are currently limited in availability and are restricted to a single genetic background. Here we report the development of a mouse model of SARS-CoV-2 based on adeno-associated virus (AAV)-mediated expression of hACE2. These mice support viral replication and exhibit pathological findings found in COVID-19 patients. Moreover, we show that type I interferons do not control SARS-CoV-2 replication in vivo but are significant drivers of pathological responses. Thus, the AAV-hACE2 mouse model enables rapid deployment for in-depth analysis following robust SARS-CoV-2 infection with authentic patient-derived virus in mice of diverse genetic backgrounds.

A lack of "morningness" predicts greater depression symptom severity over time, including in a vulnerable group of older adults family dementia caregivers (dCGs). Evidence regarding the neurobiological basis of these correlations is needed to guide future research towards biomarker-informed detection and prevention approaches. We therefore primarily aimed to identify simple resting-state biomarkers that correlated with a lack of "morningness" in dCGs.

We examined 54 dCGs (mean age=70, range 61-84; 70% female) of whom 40% were definite "morning types" according to Composite Scale of Morningness (CSM). Using a 7 Tesla resting-state sequence, we compared the functional connectivity of nodes in networks previously implicated in depression (fronto-parietal, default mode, limbic, and salience) between caregivers who were and were not "morning types."

Correcting for voxel-wise comparisons, "morning type" dCGs had less amygdala-posterior cingulate connectivity (Cohen's d=-1.3), which statistically mediated ~32%oing direction of focus around distressing content; in contrast, morning activity participation may serve to limit focus on distress. Replication and experimental studies are required to confirm these associations and their modifiability.

To investigate the 1-year risks of Staphylococcus aureus bacteremia (SAB), sepsis, and pneumonia in patients who underwent percutaneous coronary intervention and were treated with ticagrelor versus clopidogrel.

In this nationwide observational cohort study, 26,606 patients who underwent urgent or emergent percutaneous coronary intervention (January 2011-December 2017) and initiated treatment with ticagrelor (N = 20,073 [75.5%]; median age 64 years [25th-75th percentile 55-72 years]; 74.8% men) or clopidogrel (N = 6,533 [24.5%]; median age 68 years [25th-75th percentile 58-77 years]; 70.2% men) were identified using Danish nationwide registries. The 1-year standardized absolute risks of outcomes was calculated based on cause-specific Cox regression models, and average treatment effects between treatment groups were obtained as standardized differences in absolute 1-year risks. The absolute 1-year risk of SAB was 0.10% [95% CI, 0.05% to 0.15%] in the ticagrelor group and 0.29% [95% CI, 0.17% to 0.42%] in the clopidogrel group. Compared with clopidogrel, treatment with ticagrelor was associated with a significantly lower absolute 1-year risk of SAB (absolute risk difference -0.19% [95% CI, -0.32% to -0.05%], p-value 0.006). Likewise, treatment with ticagrelor was associated with a significantly lower absolute 1-year risk of sepsis (0.99% [95% CI, 0.83% to 1.14% versus 1.49% [95%CI, 1.17% to 1.80%]; absolute risk difference -0.50% [95% CI, -0.86% to -0.14%], p-value 0.007) and pneumonia (3.13% [95%CI, 2.86% to 3.39% versus 4.56% [95%CI, 4.03% to 5.08%]; absolute risk difference -1.43% [95% CI, -2.03% to -0.82%], p-value < 0.001) compared with clopidogrel.

Treatment with ticagrelor was associated with a significantly lower 1-year risk of SAB, sepsis, and pneumonia compared with clopidogrel.

Treatment with ticagrelor was associated with a significantly lower 1-year risk of SAB, sepsis, and pneumonia compared with clopidogrel.Two randomized block designs were performed to evaluate the effects of bismuth subsalicylate (BSS) and encapsulated calcium-ammonium nitrate (eCAN) on enteric methane production, nutrient digestibility, liver mineral concentration, and performance of beef cattle consuming bahiagrass hay (Paspalum notatum; ad libitum) and sugar cane molasses [1.07 kg/d; dry matter basis]. Experiment 1, used 25 crossbred steers [335 ± 46 kg of initial body weight (BW)] with a 2 × 2 + 1 factorial arrangement of treatments for two 20 d periods. Factors were nonprotein nitrogen (NPN) source (350 mg/kg BW of nitrate or 182 mg/kg BW of urea), BSS (0 or 58.4 mg/kg BW), and a negative control (NCTRL; bahiagrass hay and molasses only). Steers were re-randomized for a second period (n = 10/treatment total). Intake, apparent total tract digestibility and enteric methane were evaluated. Experiment 2 used 75 crossbred heifers in 25 pens (3 heifers/pen; 279 ± 57 kg of initial BW), consuming the same diet and treatments as experiment 1, to dand BSS had lesser final BW compared with heifers consuming urea and BSS. While eCAN may be a viable resource for mitigating enteric CH4 production of forage-fed cattle, the negative effects on digestibility should be considered. Furthermore, BSS, at the amount provided, appears to have no negative effects on digestibility of nutrients in forage-fed cattle; however, there may be deleterious impacts on performance depending upon what nitrogen source is supplied.

Shoulder pain and dysfunction are highly prevalent after neck dissection in the treatment of head and neck cancer (HNC). They can lead to muscle weakness, limited range of motion, and shoulder tilt and pain, which can reduce patient functioning. The purpose of this study was to evaluate the effectiveness of rehabilitation interventions for shoulder dysfunction in patients with surgically treated HNC.

A search of principal databases (MEDLINE, Embase, CENTRAL, LILACS, IBECS, PEDro, and SciELO) was conducted, in addition to hand searches and a search of gray literature, for all randomized clinical trials (RCTs) published before February 2020. Two authors independently selected all relevant studies. read more The 7 RCTs fulfilling all inclusion and exclusion criteria were assessed for risk of bias and certainty of evidence using the Cochrane Collaboration risk-of-bias tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool, respectively.

Moderate-certainty evidence suggests that prd improve function. This study will help researchers design clinical trials to determine whether treatments such as acupuncture and early physical therapy also could be effective in treating this population.

These study results show that people with head and neck cancer can benefit from gradually increased resistance training to reduce shoulder pain and improve function. This study will help researchers design clinical trials to determine whether treatments such as acupuncture and early physical therapy also could be effective in treating this population.The recent development and regulatory approval of a variety of serological assays indicating the presence of antibodies against severe acute respiratory syndrome coronavirus 2 has led to rapid and widespread implementation of seroprevalence studies. Accurate estimates of seroprevalence are needed to model transmission dynamics and estimate mortality rates. Furthermore, seroprevalence levels in a population help guide policy surrounding reopening efforts. The literature to date has focused heavily on issues surrounding the quality of seroprevalence tests and less on the sampling methods that ultimately drive the representativeness of resulting estimates. Seroprevalence studies based on convenience samples are being reported widely and extrapolated to larger populations for the estimation of total coronavirus disease 2019 (COVID-19) infections, comparisons of prevalence across geographic regions, and estimation of mortality rates. In this viewpoint, we discuss the pitfalls that can arise with the use of convenience samples and offer guidance for moving towards more representative and timely population estimates of COVID-19 seroprevalence.Ultraconserved genomic elements (UCEs) are generally treated as independent loci in phylogenetic analyses. The identification pipeline for UCE probes does not require prior knowledge of genetic identity, only selecting loci that are highly conserved, single copy, without repeats, and of a particular length. Here, we characterized UCEs from 11 phylogenomic studies across the animal tree of life, from birds to marine invertebrates. We found that within vertebrate lineages, UCEs are mostly intronic and intergenic, while in invertebrates, the majority are in exons. We then curated four different sets of UCE markers by genomic category from five different studies including birds, mammals, fish, Hymenoptera (ants, wasps, and bees), and Coleoptera (beetles). Of genes captured by UCEs, we find that many are represented by two or more UCEs, corresponding to nonoverlapping segments of a single gene. We considered these UCEs to be nonindependent, merged all UCEs that belonged to a particular gene, constructed gene and species trees, and then evaluated the subsequent effect of merging cogenic UCEs on gene and species tree reconstruction.

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