National Beef Quality Audit-2022 Phase 1: face-to-face and digital interviews.

The National Beef Quality Audit (NBQA) has been conducted regularly since 1991 to assess and benchmark quality in the U.S. beef industry, with the most recent iteration conducted in 2022. The goal of NBQA Phase I is to evaluate what needs to be managed to improve beef quality and demand. Interviews (n = 130) of industry personnel were conducted with the aid of routing software. In total, packers (n = 24), retailers (n = 20), further processors (n = 26), foodservice (n = 18), and allied government agencies and trade organizations (n = 42) were interviewed. Interviews were routed in software based on interviewee involvement in either the fed steer and heifer market cow and bull sectors, or both. Interviews were structured to elicit random responses in the order of determining "must-have" criteria (quality factors that are required to make a purchase), best/worst ranking (of quality factors based on importance), how interviewees defined quality terms, a strength, weakness, opportunities, threats (SWOT) analysis, general beef industry questions, and sustainability goals (the latter four being open-ended). Quality factors were 1) visual characteristics, 2) cattle genetics, 3) food safety, 4) eating satisfaction, 5) animal well-being, 6) weight and size, and 7) lean, fat, and bone. Best/worst analysis revealed that "food safety" was the most (P < 0.05) important factor in beef purchasing decisions for all market sectors and frequently was described as "everything" and "a way of business." Culture surrounding food safety changed compared to previous NBQAs with interviewees no longer considering food safety as a purchasing criterion, but rather as a market expectation. The SWOT analysis indicated that "eating quality of U.S. beef" was the greatest strength, and cited that educating both consumers and producers on beef production would benefit the industry. Irrespective of whether companies' products were fed or market cow/bull beef, respondents said that they believed "environmental concerns" were among the major threats to the industry. Perceived image of the beef industry in the market sectors has improved since NBQA-2016 for both fed cattle and market cow/bull beef.

Identifying Predictors of Initial Surgical Failure during Minimally Invasive Endoscopic Intracerebral Hemorrhage Evacuation.

Background and Purpose: Intracerebral hemorrhage (ICH) is a common and severe disease with high rates of morbidity and mortality; however, minimally invasive surgical (MIS) hematoma evacuation represents a promising avenue for treatment. In February of 2019, the MISTIE III study found that stereotactic thrombolysis with catheter drainage did not benefit patients with supratentorial spontaneous ICH but that a clinical benefit may be present when no more than 15 mL of hematoma remains at the end of treatment. Intraoperative CT (iCT) imaging has the ability to assess whether or not this surgical goal has been met in real time, allowing for operations to add additional CT-informed 'evacuation periods' (EPs) to achieve the surgical goal. Here, we report on the frequency and predictors of initial surgical failure on at least one iCT requiring additional EPs in a large cohort of patients undergoing endoscopic minimally invasive ICH evacuation with the SCUBA technique. Methods: All patients who underwent minimally invasive endoscopic evacuation of supratentorial spontaneous ICH in a major health system between December 2015 and October 2018 were included in this study. Patient demographics, clinical and radiographic features, procedural details, and outcomes were analyzed retrospectively from a prospectively collected database. Procedures were characterized as initially successful when the first iCT demonstrated that surgical success had been achieved and initially unsuccessful when the surgical goal was not achieved, and additional EPs were performed. The surgical goal was prospectively identified in December of 2015 as leaving no more than 20% of the preoperative hematoma volume at the end of the procedure. Descriptive statistics and regression analyses were performed to identify predictors of initial failure and secondary rescue. Results: Patients (100) underwent minimally invasive endoscopic ICH evacuation in the angiography suite during the study time period. In 14 cases, the surgical goal was not met on the first iCT and multiple Eps were performed; in 10 cases the surgical goal was not met, and no additional EPs were performed. In 14 cases, the surgical goal was never achieved. When additional EPs were performed, a rescue rate of 71.4% (10/14) was seen, bringing the total percentage of cases meeting the surgical goal to 86% across the entire cohort. Cases in which the surgical goal was not achieved were significantly associated with older patients (68 years vs. 60 years; p = 0.0197) and higher rates of intraventricular hemorrhage (34.2% vs. 70.8%; p = 0.0021). Cases in which the surgical goal was rescued from initial failure had similar levels of IVH, suggesting that these additional complexities can be overcome with the use of additional iCT-informed EPs. Conclusions: Initial and ultimate surgical failure occurs in a small percentage of patients undergoing minimally invasive endoscopic ICH evacuation. The use of intraoperative imaging provides an opportunity to evaluate whether or not the surgical goal has been achieved, and to continue the procedure if the surgeon feels that more evacuation is achievable. Now that level-one evidence exists to target a surgical evacuation goal during minimally invasive ICH evacuation, intraoperative imaging, such as iCT, plays an important role in aiding the surgical team to achieve the surgical goal.

A Report of a Rare Case of Rapidly Progressing Immature Teratoma With Associated Splenic Metastasis and Gliomatosis Peritonei.

Gliomatosis peritonei (GP) is a rare condition of mature glial tissue within the peritoneum often associated with immature teratomas. This was a case of rapid progression of immature teratoma with splenic lesions and associated GP. The patient was a 21-year-old female who presented with abdominal pain and CT imaging showing suspected malignant teratoma. The patient underwent exploratory laparotomy with fertility-sparing debulking surgery and was diagnosed with stage IIIC grade 3 immature teratoma. She then received adjuvant chemotherapy with bleomycin, etoposide, and cisplatin. Surveillance imaging demonstrated a non-avid splenic lesion. The tumor markers remained normal. She underwent robotic splenectomy and partial peritonectomy with intra-operative findings revealing numerous peritoneal nodules. Follow-up surveillance imaging showed no further lesions. The final histopathology examination demonstrated mature and mesenchymal neural tissue consistent with residual teratoma and no immature elements. The specimens were largely composed of nodules of mature glial tissue and focal areas of mature neuronal tissue. Immunohistochemistry demonstrated glial fibrillary acidic protein (GFAP) and S100 expression, confirming neural origin tissue. Octamer-binding transcription factor 4 (OCT-4) immunostain was negative which confirmed the absence of immature neural tissue. We report a rare case of rapid progression of immature teratoma with splenic metastasis and peritoneal nodules found ultimately to be mature teratoma and associated GP. Recognition of rapidly growing teratoma with new lesions as potential GP is imperative to prevent misdiagnosis as recurrence or progression of disease. This case was treated with secondary debulking surgery which should be a consideration of management if surgically feasible.

Chronic metabolic stress drives developmental programs and loss of tissue functions in non-transformed liver that mirror tumor states and stratify survival.

Under chronic stress, cells must balance competing demands between cellular survival and tissue function. In metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD/NASH), hepatocytes cooperate with structural and immune cells to perform crucial metabolic, synthetic, and detoxification functions despite nutrient imbalances. While prior work has emphasized stress-induced drivers of cell death, the dynamic adaptations of surviving cells and their functional repercussions remain unclear. Namely, we do not know which pathways and programs define cellular responses, what regulatory factors mediate (mal)adaptations, and how this aberrant activity connects to tissue-scale dysfunction and long-term disease outcomes. Here, by applying longitudinal single-cell multi -omics to a mouse model of chronic metabolic stress and extending to human cohorts, we show that stress drives survival-linked tradeoffs and metabolic rewiring, manifesting as shifts towards development-associated states in non-transformed hepatocytes with accompanying decreases in their professional functionality. Diet-induced adaptations occur significantly prior to tumorigenesis but parallel tumorigenesis-induced phenotypes and predict worsened human cancer survival. Through the development of a multi -omic computational gene regulatory inference framework and human in vitro and mouse in vivo genetic perturbations, we validate transcriptional (RELB, SOX4) and metabolic (HMGCS2) mediators that co-regulate and couple the balance between developmental state and hepatocyte functional identity programming. Our work defines cellular features of liver adaptation to chronic stress as well as their links to long-term disease outcomes and cancer hallmarks, unifying diverse axes of cellular dysfunction around core causal mechanisms.

SARS-CoV-2 viral liver aggregates and scarce parenchymal infection implicate systemic disease as a driver of abnormal liver function.

BACKGROUND: Liver function tests (LFTs) are elevated in >50% of hospitalized individuals infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), with increased enzyme levels correlating with a more severe COVID-19 course. Despite these observations, evaluations of viral presence within liver parenchyma and viral impact on liver function remain controversial. METHODS AND RESULTS: Our work is a comprehensive immunopathological evaluation of liver tissue from 33 patients with severe, and ultimately fatal, cases of SARS-CoV-2 infection. Coupled with clinical data, we reveal the absence of SARS-CoV-2 infection in cholangiocytes and hepatocytes despite dramatic systemic viral presence. Critically, we identify significant focal viral sinusoidal aggregates in 2/33 patients and single viral RNA molecules circulating in the hepatic sinusoids of 15/33 patients. Utilizing co-immunofluorescence, focal viral liver aggregates in patients with COVID-19 were colocalized to platelet and fibrin clots, indicating the presence of virus-containing sinusoidal microthrombi. Furthermore, this patient cohort, from the initial months of the COVID-19 pandemic, demonstrates a general downtrend of LFTs over the course of the study timeline and serves as a remarkable historical time point of unattenuated viral replication within patients. CONCLUSIONS: Together, our findings indicate that elevated LFTs found in our patient cohort are not due to direct viral parenchymal infection with SARS-CoV-2 but rather likely a consequence of systemic complications of COVID-19. This work aids in the clinical treatment considerations of patients with SARS-CoV-2 as therapies for these patients may be considered in terms of their direct drug hepatotoxity rather than worsening hepatic function due to direct infection.

Preoperative cerebral angiography nearly doubles the rate of diffusion-weighted imaging lesion detection following minimally invasive surgery for intracerebral hemorrhage.

BACKGROUND: Diffusion-weighted imaging (DWI) lesions have been linked to poor outcomes after intracerebral hemorrhage (ICH). We aimed to assess the impact of cerebral digital subtraction angiography (DSA) on the presence of DWI lesions in patients who underwent minimally invasive surgery (MIS) for ICH. METHODS: Retrospective chart review was performed on ICH patients treated with MIS in a single health system from 2015 to 2021. One hundred and seventy consecutive patients who underwent postoperative MRIs were reviewed. Univariate analyses were conducted to determine associations. Variables with p<0.05 were included in multivariate analyses. RESULTS: DWI lesions were present in 88 (52%) patients who underwent MIS for ICH. Of the 83 patients who underwent preoperative DSA, 56 (67%) patients demonstrated DWI lesions. In this DSA cohort, older age, severe leukoaraiosis, larger preoperative hematoma volume, and increased presenting National Institutes of Health Stroke Score (NIHSS) were independently associated with DWI lesion identification (p<0.05). In contrast, of 87 patients who did not undergo DSA, 32 (37%) patients demonstrated DWI lesions on MRI. In the non-DSA cohort, presenting systolic blood pressure, intraventricular hemorrhage, and NIHSS were independently associated with DWI lesions (p<0.05). Higher DWI lesion burden was independently associated with poor modified Rankin Scale (mRS) at 6 months on a univariate (p=0.02) and multivariate level (p=0.02). CONCLUSIONS: In this cohort of ICH patients who underwent minimally invasive evacuation, preprocedural angiography was associated with the presence of DWI lesions on post-ICH evacuation MRI. Furthermore, the burden of DWI lesions portends a worse prognosis after ICH.

Early and effective intracerebral hemorrhage evacuation is associated with a lower 1-year residual cavity volume and better functional outcomes.

BACKGROUND: We explored the clinical significance of the residual hematoma cavity 1 year after minimally invasive intracerebral hemorrhage (ICH) evacuation. METHODS: Patients presenting with spontaneous supratentorial ICH were evaluated for minimally invasive surgical evacuation. Inclusion criteria included age ≥18 years, preoperative hematoma volume (Hv) ≥15 mL, presenting National Institutes of Health Stroke Scale score ≥6, and premorbid modified Rankin Scale (mRS) score ≤3. Patients with longitudinal CT scans at least 3 months after evacuation were included in the study. Remnant cavity volumes (Cv) after evacuation were computed using semi-automatic volumetric segmentation software. Relative cavity volume (rCv) was defined as the ratio of the preoperative Hv to the remnant Cv. RESULTS: 108 patients with a total of 484 head CT scans were included in the study. The median postoperative Cv was 2.4 (IQR 0.0-11) mL, or just 6% (0-33%) of the preoperative Hv. The median residual Cv on the final head CT scan a median of 13 months (range 11-27 months) after surgery had increased to 9.4 (IQR 3.1-18) mL, or 25% (10-60%) of the preoperative Hv. rCv on the final head CT scan was negatively associated with measures of operative success including evacuation percentage, postoperative Hv ≤15 mL, and decreased time from ictus to evacuation. rCv on the final head CT scan was also associated with a worse 6-month functional outcome (ß per mRS point 17.6%, P<0.0001; area under the receiver operating characteristic curve 0.91). CONCLUSION: After minimally invasive ICH evacuation the hematoma lesion decompresses significantly, with a residual Cv just 6% of the original lesion, but then gradually increases in size over time. Early and high percentage ICH evacuation may reduce the remnant Cv over time which, in turn, is associated with improved functional outcomes.

Postpartum scarcity-adversity inflicts sex-specific cerebellar adaptations and reward behaviors in adolescence.

Early life adversity in the form of poor postnatal care is a major developmental stressor impacting behavior later in life. Previous studies have shown the impact of early life stress on neurobehavioral abnormalities. Specifically, research has demonstrated how limited bedding and nesting (LBN) materials can cause behavioral deficits in adulthood. There is, however, a limited understanding of how LBN influences sex-specific neurobehavioral adaptation in adolescence, a developmental stage susceptible to psychiatric diseases including substance use disorder. LBN and stress-naive c57BL/6 adolescent male and female mouse offspring were tested for a battery of behaviors including open field, novel object recognition, elevated plus maze, social preference, and morphine-induced conditioned place preference. There was a significant sex-specific deficit in social preference in male mice exposed to LBN compared to stress-naïve counterparts and both LBN males and females had a higher preference towards the drug-paired chamber in the morphine-induced conditioned place preference test. These behavioral deficits were concomitant with sex-specific increases in the transcription factor, Klf9 in the deep cerebellar nuclei (DCN) of males. Further, mRNA levels of the circadian gene Bmal1, which is known to be transcriptionally regulated by Klf9, were decreased in the DCN. Since Bmal1 has recently been implicated in extracellular matrix modulation, we examined perineuronal nets (PNN) and observed depleted PNN in the DCN of males but not female LBN mice. Overall, we provide a novel understanding of how postpartum adversity impinges on the cerebellar extracellular matrix homeostasis, likely, through disruption of the circadian axis by Klf9 that might underlie sex-specific behavioral adaptations in adolescence.

Minimally Invasive Intracerebral Hemorrhage Evacuation Improves Pericavity Cerebral Blood Volume.

Cerebral blood volume mapping can characterize hemodynamic changes within brain tissue, particularly after stroke. This study aims to quantify blood volume changes in the perihematomal parenchyma and pericavity parenchyma after minimally invasive intracerebral hemorrhage evacuation (MIS for ICH). Thirty-two patients underwent MIS for ICH with pre- and post-operative CT imaging and intraoperative perfusion imaging (DynaCT PBV Neuro, Artis Q, Siemens). The pre-operative and post-operative CT scans were segmented using ITK-SNAP software to calculate hematoma volumes and to delineate the pericavity tissue. Helical CT segmentations were registered to cone beam CT data using elastix software. Mean blood volumes were computed inside subvolumes by dilating the segmentations at increasing distances from the lesion. Pre-operative perihematomal blood volumes and post-operative pericavity blood volumes (PBV) were compared. In 27 patients with complete imaging, post-operative PBV significantly increased within the 6-mm pericavity region after MIS for ICH. The mean relative PBV increased by 21.6 and 9.1% at 3 mm and 6 mm, respectively (P = 0.001 and 0.016, respectively). At the 9-mm pericavity region, there was a 2.83% increase in mean relative PBV, though no longer statistically significant. PBV analysis demonstrated a significant increase in pericavity cerebral blood volume after minimally invasive ICH evacuation to a distance of 6 mm from the border of the lesion.

Characterization of length of stay after minimally invasive endoscopic intracerebral hemorrhage evacuation.

BACKGROUND: Minimally invasive evacuation may help ameliorate outcomes after intracerebral hemorrhage (ICH). However, hospital length of stay (LOS) post-evacuation is often long and costly. OBJECTIVE: To examine factors associated with LOS in a large cohort of patients who underwent minimally invasive endoscopic evacuation. METHODS: Patients presenting to a large health system with spontaneous supratentorial ICH qualified for minimally invasive endoscopic evacuation if they met the following inclusion criteria: age ≥18, premorbid modified Rankin Scale (mRS) score ≤3, hematoma volume ≥15 mL, and presenting National Institutes of Health Stroke Scale (NIHSS) score ≥6. Demographic, clinical, radiographic, and operative characteristics were included in a multivariate logistic regression for hospital and ICU LOS dichotomized into short and prolonged stay at 14 and 7 days, respectively. RESULTS: Among 226 patients who underwent minimally invasive endoscopic evacuation, the median intensive care unit and hospital LOS were 8 (4-15) days and 16 (9-27) days, respectively. A greater extent of functional impairment on presentation (OR per NIHSS point 1.10 (95% CI 1.04 to 1.17), P=0.007), concurrent intraventricular hemorrhage (OR=2.46 (1.25 to 4.86), P=0.02), and deep origin (OR=per point 2.42 (1.21 to 4.83), P=0.01) were associated with prolonged hospital LOS. A longer delay from ictus to evacuation (OR per hour 1.02 (1.01 to 1.04), P=0.007) and longer procedure time (OR per hour 1.91 (1.26 to 2.89), P=0.002) were associated with prolonged ICU LOS. Prolonged hospital and ICU LOS were in turn longitudinally associated with a lower rate of discharge to acute rehabilitation (40% vs 70%, P<0.0001) and worse 6-month mRS outcomes (5 (4-6) vs 3 (2-4), P<0.0001). CONCLUSIONS: We present factors associated with prolonged LOS, which in turn was associated with poor long-term outcomes. Factors associated with LOS may help to inform patient and clinician expectations of recovery, guide protocols for clinical trials, and select suitable populations for minimally invasive endoscopic evacuation.

Damage-induced pyroptosis drives endog thymic regeneration via induction of Foxn1 by purinergic receptor activation.

Endogenous thymic regeneration is a crucial process that allows for the renewal of immune competence following stress, infection or cytoreductive conditioning. Fully understanding the molecular mechanisms driving regeneration will uncover therapeutic targets to enhance regeneration. We previously demonstrated that high levels of homeostatic apoptosis suppress regeneration and that a reduction in the presence of damage-induced apoptotic thymocytes facilitates regeneration. Here we identified that cell-specific metabolic remodeling after ionizing radiation steers thymocytes towards mitochondrial-driven pyroptotic cell death. We further identified that a key damage-associated molecular pattern (DAMP), ATP, stimulates the cell surface purinergic receptor P2Y2 on cortical thymic epithelial cells (cTECs) acutely after damage, enhancing expression of Foxn1, the critical thymic transcription factor. Targeting the P2Y2 receptor with the agonist UTPγS promotes rapid regeneration of the thymus in vivo following acute damage. Together these data demonstrate that intrinsic metabolic regulation of pyruvate processing is a critical process driving thymus repair and identifies the P2Y2 receptor as a novel molecular therapeutic target to enhance thymus regeneration.

Long-term functional independence after minimally invasive endoscopic intracerebral hemorrhage evacuation.

OBJECTIVE: Intracerebral hemorrhage (ICH) is a devastating form of stroke with no proven treatment. However, minimally invasive endoscopic evacuation is a promising potential therapeutic option for ICH. Herein, the authors examine factors associated with long-term functional independence (modified Rankin Scale [mRS] score ≤ 2) in patients with spontaneous ICH who underwent minimally invasive endoscopic evacuation. METHODS: Patients with spontaneous supratentorial ICH who had presented to a large urban healthcare system from December 2015 to October 2018 were triaged to a central hospital for minimally invasive endoscopic evacuation. Inclusion criteria for this study included age ≥ 18 years, hematoma volume ≥ 15 ml, National Institutes of Health Stroke Scale (NIHSS) score ≥ 6, premorbid mRS score ≤ 3, and time from ictus ≤ 72 hours. Demographic, clinical, and radiographic factors previously shown to impact functional outcome in ICH were included in a retrospective univariate analysis with patients dichotomized into independent (mRS score ≤ 2) and dependent (mRS score ≥ 3) outcome groups, according to 6-month mRS scores. Factors that reached a threshold of p < 0.05 in a univariate analysis were included in a multivariate logistic regression. RESULTS: A total of 90 patients met the study inclusion criteria. The median preoperative hematoma volume was 41 (IQR 27-65) ml and the median postoperative volume was 1.2 (0.3-7.5) ml, resulting in a median evacuation percentage of 97% (85%-99%). The median hospital length of stay was 17 (IQR 9-25) days, and 8 (9%) patients died within 30 days of surgery. Twenty-four (27%) patients had attained functional independence by 6 months. Factors independently associated with long-term functional independence included lower NIHSS score at presentation (OR per point 0.78, 95% CI 0.67-0.91, p = 0.002), lack of intraventricular hemorrhage (IVH; OR 0.20, 95% CI 0.05-0.77, p = 0.02), and shorter time to evacuation (OR per hour 0.95, 95% CI 0.91-0.99, p = 0.007). Specifically, patients who had undergone evacuation within 24 hours of ictus demonstrated an mRS score ≤ 2 rate of 36% and were associated with an increased likelihood of long-term independence (OR 17.7, 95% CI 1.90-164, p = 0.01) as compared to those who had undergone evacuation after 48 hours. CONCLUSIONS: In a single-center minimally invasive endoscopic ICH evacuation cohort, NIHSS score on presentation, lack of IVH, and shorter time to evacuation were independently associated with functional independence at 6 months. Factors associated with functional independence may help to better predict populations suitable for minimally invasive endoscopic evacuation and guide protocols for future clinical trials.

Embryonic alcohol exposure disrupts the ubiquitin-proteasome system.

Ethanol (EtOH) is a commonly encountered teratogen that can disrupt organ development and lead to fetal alcohol spectrum disorders (FASDs); many mechanisms of developmental toxicity are unknown. Here, we used transcriptomic analysis in an established zebrafish model of embryonic alcohol exposure (EAE) to identify the ubiquitin-proteasome system (UPS) as a critical target of EtOH during development. Surprisingly, EAE alters 20S, 19S, and 11S proteasome gene expression and increases ubiquitylated protein load. EtOH and its metabolite acetaldehyde decrease proteasomal peptidase activity in a cell type-specific manner. Proteasome 20S subunit ß 1 (psmb1hi2939Tg) and proteasome 26S subunit, ATPase 6 (psmc6hi3593Tg), genetic KOs define the developmental impact of decreased proteasome function. Importantly, loss of psmb1 or psmc6 results in widespread developmental abnormalities resembling EAE phenotypes, including growth restriction, abnormal craniofacial structure, neurodevelopmental defects, and failed hepatopancreas maturation. Furthermore, pharmacologic inhibition of chymotrypsin-like proteasome activity potentiates the teratogenic effects of EAE on craniofacial structure, the nervous system, and the endoderm. Our studies identify the proteasome as a target of EtOH exposure and signify that UPS disruptions contribute to craniofacial, neurological, and endodermal phenotypes in FASDs.

A preliminary exploration of the impact of experiential learning on animal science undergraduates' perceptions of humane stunning and slaughter.

It is essential to educate students about humane slaughter as it is a critical component of livestock production, particularly for animal science students who represent future stakeholders in agriculture. There is limited research about the effects of experiential learning on student comfort in participating in education regarding sensitive, yet important topics in the animal sciences. A survey was developed to investigate how a teaching module using an experiential learning activity to teach undergraduates about the slaughter process affected student perceptions of stunning and slaughter. Students enrolled in an animal science course, in which live animals and carcasses are evaluated, were surveyed before and after a teaching module. The module included a lecture about proper stunning and a laboratory activity in which the students had the opportunity to shoot a captive bolt stunner on both model and carcass heads. Respondents completed a pre-survey, attended the laboratory activity, and completed a post-survey; 29 survey responses were recorded. Most respondents were women (23, 79.3%) between the ages of 18 and 21 years (25, 86.2%) and in their first year of college (11, 37.9%). The majority of respondents (22, 75.9%) reported using the captive bolt stunner to stun the model heads during the laboratory activity. After participating in the module, all students strongly agreed that "stunning" is a critical component of livestock slaughter (29, 100%) and most agreed that "stunning is a humane process that ensures animal welfare during the slaughter process" (25, 86.2%). The majority of respondents strongly agreed that the "humane stunning simulation was beneficial to their learning about livestock slaughter" (21, 72.4%) and "improved their understanding of slaughter" (16, 55.2%). Almost all of the survey respondents either agreed or strongly agreed that "the model heads and captive bolt demonstration made them more comfortable with the slaughter process" (14, 48.3%; 14, 48.3%, respectively). This research suggests that experiential learning opportunities are potentially effective teaching strategies for educating undergraduates about the slaughter process. Future research should focus on practical ways to integrate new teaching methods into existing animal science curricula, as this will be critical for educating students on important topics in livestock production and increasing student comfort with sensitive material.

Renal Cell Carcinoma with Testicular Metastases: A Case Report and Review of the Literature.

Renal cell carcinoma (RCC) metastases to the testicle are an extremely rare clinical entity. Here, we describe the case of a man with metastatic RCC who developed a new testicular mass. Pathologic analysis after surgical removal of this testicle confirmed the diagnosis of metastatic RCC. This report highlights the unique diagnostic and therapeutic challenges associated with such a disease process.

Accuracy of artificial intelligence for the detection of intracranial hemorrhage and chronic cerebral microbleeds: a systematic review and pooled analysis.

BACKGROUND: Artificial intelligence (AI)-driven software has been developed and become commercially available within the past few years for the detection of intracranial hemorrhage (ICH) and chronic cerebral microbleeds (CMBs). However, there is currently no systematic review that summarizes all of these tools or provides pooled estimates of their performance. METHODS: In this PROSPERO-registered, PRISMA compliant systematic review, we sought to compile and review all MEDLINE and EMBASE published studies that have developed and/or tested AI algorithms for ICH detection on non-contrast CT scans (NCCTs) or MRI scans and CMBs detection on MRI scans. RESULTS: In total, 40 studies described AI algorithms for ICH detection in NCCTs/MRIs and 19 for CMBs detection in MRIs. The overall sensitivity, specificity, and accuracy were 92.06%, 93.54%, and 93.46%, respectively, for ICH detection and 91.6%, 93.9%, and 92.7% for CMBs detection. Some of the challenges encountered in the development of these algorithms include the laborious work of creating large, labeled and balanced datasets, the volumetric nature of the imaging examinations, the fine tuning of the algorithms, and the reduction in false positives. CONCLUSIONS: Numerous AI-driven software tools have been developed over the last decade. On average, they are characterized by high performance and expert-level accuracy for the diagnosis of ICH and CMBs. As a result, implementing these tools in clinical practice may improve workflow and act as a failsafe for the detection of such lesions. REGISTRATION-URL: https://www.crd.york.ac.uk/prospero/ Unique Identifier: CRD42021246848.

Epigenomic profiling of glucocorticoid responses identifies cis-regulatory disruptions impacting steroid resistance in childhood acute lymphoblastic leukemia.

Glucocorticoids (GCs) are a mainstay of contemporary, multidrug chemotherapy in the treatment of childhood acute lymphoblastic leukemia (ALL), and resistance to GCs remains a major clinical concern. Resistance to GCs is predictive of ALL relapse and poor clinical outcome, and therefore represents a major hurdle limiting further improvements in survival rates. While advances have been made in identifying genes implicated in GC resistance, there remains an insufficient understanding of the impact of cis-regulatory disruptions in resistance. To address this, we mapped the gene regulatory response to GCs in two ALL cell lines using functional genomics and high-throughput reporter assays and identified thousands of GC-responsive changes to chromatin state, including the formation of over 250 GC-responsive super-enhancers and a depletion of AP-1 bound cis-regulatory elements implicated in cell proliferation and anti-apoptotic processes. By integrating our GC response maps with genetic and epigenetic datasets in primary ALL cells from patients, we further uncovered cis-regulatory disruptions at GC-responsive genes that impact GC resistance in childhood ALL. Overall, these data indicate that GCs initiate pervasive effects on the leukemia epigenome, and that alterations to the GC gene regulatory network contribute to GC resistance.

Initial Experience With the NICO Myriad Device for Minimally Invasive Endoscopic Evacuation of Intracerebral Hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) is a devastating form of stroke for which there is no consensus treatment. Although open craniotomy has been explored as a surgical treatment option, multiple minimally invasive (MIS) techniques have been developed including endoscopic evacuation. An adjunctive aspiration device can be used through the working channel to provide an additional degree of freedom and increased functionality regarding clot manipulation and morcellation. OBJECTIVE: To report our single-center technical experience with the Myriad device used as an adjunctive aspiration device during endoscopic ICH evacuation in an exploratory case series. METHODS: Demographic, clinical, and radiographic data were collected on patients who underwent MIS endoscopic ICH evacuation using the Myriad aspiration device from December 2018 to March 2019. RESULTS: Eight patients underwent ICH evacuation with the Myriad aspiration device. Bleeding was confined to the cortex in 4 patients, subcortical region in 2 patients, and the cerebellum in 2 patients. One of the cerebellar cases also underwent suboccipital craniotomy. The mean preoperative hematoma volume was 65.1 ± 68.9 mL, and the median postoperative volume was 7.6 ± 9.0 mL, for an average evacuation percentage of 88.1% ± 12.1%. In 75% of the cases, a bleeding vessel was identified and treated with either cautery or irrigation alone. There was no hemorrhagic recurrence or mortality within 30 days. CONCLUSION: Data from this initial experience suggest that MIS endoscopic ICH evacuation with the NICO Myriad aspiration device is feasible and technically effective. Multicenter exposure is necessary to verify broader applicability.

Amino acid stress response genes promote L-asparaginase resistance in pediatric acute lymphoblastic leukemia.

Understanding the genomic and epigenetic mechanisms of drug resistance in pediatric acute lymphoblastic leukemia (ALL) is critical for further improvements in treatment outcomes. The role of transcriptomic response in conferring resistance to l-asparaginase (LASP) is poorly understood beyond asparagine synthetase (ASNS). We defined reproducible LASP response genes in LASP-resistant and LASP-sensitive ALL cell lines as well as primary leukemia samples from newly diagnosed patients. Defining target genes of the amino acid stress response-related transcription factor activating transcription factor 4 (ATF4) in ALL cell lines using chromatin immunoprecipitation sequencing (ChIP-seq) revealed 45% of genes that changed expression after LASP treatment were direct targets of the ATF4 transcription factor, and 34% of these genes harbored LASP-responsive ATF4 promoter binding events. SLC7A11 was found to be a response gene in cell lines and patient samples as well as a direct target of ATF4. SLC7A11 was also one of only 2.4% of LASP response genes with basal level gene expression that also correlated with LASP ex vivo resistance in primary leukemia cells. Experiments using chemical inhibition of SLC7A11 with sulfasalazine, gene overexpression, and partial gene knockout recapitulated LASP resistance or sensitivity in ALL cell lines. These findings show the importance of assessing changes in gene expression following treatment with an antileukemic agent for its association with drug resistance and highlight that many response genes may not differ in their basal expression in drug-resistant leukemia cells.