A novel method for culturing enteric neurons generates neurospheres containing functional myenteric neuronal subtypes.

BACKGROUND: The enteric nervous system (ENS) is comprised of neurons, glia, and neural progenitor cells that regulate essential gastrointestinal functions. Advances in high-efficiency enteric neuron culture would facilitate discoveries surrounding ENS regulatory processes, pathophysiology, and therapeutics. NEW METHOD: Development of a simple, robust, one-step method to culture murine enteric neurospheres in a 3D matrix that supports neural growth and differentiation. RESULTS: Myenteric plexus cells isolated from the entire length of adult murine small intestine formed ≥3000 neurospheres within 7 days. Matrigel-embedded neurospheres exhibited abundant neural stem and progenitor cells expressing Sox2, Sox10 and Msi1 by day 4. By day 5, neural progenitor cell marker Nestin appeared in the periphery of neurospheres prior to differentiation. Neurospheres produced extensive neurons and neurites, confirmed by Tubulin beta III, PGP9.5, HuD/C, and NeuN immunofluorescence, including neural subtypes Calretinin, ChAT, and nNOS following 8 days of differentiation. Individual neurons within and external to neurospheres generated depolarization induced action potentials which were inhibited in the presence of sodium channel blocker, Tetrodotoxin. Differentiated neurospheres also contained a limited number of glia and endothelial cells. COMPARISON WITH EXISTING METHODS: This novel one-step neurosphere growth and differentiation culture system, in 3D format (in the presence of GDNF, EGF, and FGF2), allows for ∼2-fold increase in neurosphere count in the derivation of enteric neurons with measurable action potentials. CONCLUSION: Our method describes a novel, robust 3D culture of electrophysiologically active enteric neurons from adult myenteric neural stem and progenitor cells.

Evidence for an event-integration window: A cognitive temporal window supports flexible integration of multimodal events.

Just as the perception of simple events such as clapping hands requires a linkage of sound with movements that produce the sound, the integration of more complex events such as describing how to give an injection requires a linkage between the instructor's utterances and their actions. However, the mechanism for integrating these complex multimodal events is unclear. For example, it is possible that predictive temporal relationships are important for multimodal event understanding, but it is also possible that this form of understanding arises more from meaningful causal between-event links that are temporally unspecified. This latter approach might be supported by a cognitive temporal window within which multimodal event information integrates flexibly with few default commitments about specific temporal relationships. To test this hypothesis, we assessed the consequences of disrupting temporal relationships between instructors' actions and their speech in both narrated screen-capture instructional videos (Experiment 1) and live-action instructional videos (Experiment 2) by displacing the audio channel forward or backward relative to the video by 0, 1, 3, or 7 s. We assessed learning, event segmentation, disruption awareness, segmentation uncertainty, and perceived workload. Across two experiments, 7-s temporal disruptions consistently increased uncertainty and workload and decreased learning in Experiment 2. None of these effects appeared for 3-s disruptions, which were barely detectable. One-second disruptions produced no effects and were undetectable, even though much intraevent information falls within this range. Our results suggest the presence of an event-integration window that supports the integration of events independent of constraining temporal relationships between subevents. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A prototype scintillator real-time beam monitor for ultra-high dose rate radiotherapy.

BACKGROUND: FLASH Radiotherapy (RT) is an emergent cancer RT modality where an entire therapeutic dose is delivered at more than 1000 times higher dose rate than conventional RT. For clinical trials to be conducted safely, a precise and fast beam monitor that can generate out-of-tolerance beam interrupts is required. This paper describes the overall concept and provides results from a prototype ultra-fast, scintillator-based beam monitor for both proton and electron beam FLASH applications. PURPOSE: A FLASH Beam Scintillator Monitor (FBSM) is being developed that employs a novel proprietary scintillator material. The FBSM has capabilities that conventional RT detector technologies are unable to simultaneously provide: (1) large area coverage; (2) a low mass profile; (3) a linear response over a broad dynamic range; (4) radiation hardness; (5) real-time analysis to provide an IEC-compliant fast beam-interrupt signal based on true two-dimensional beam imaging, radiation dosimetry and excellent spatial resolution. METHODS: The FBSM uses a proprietary low mass, less than 0.5 mm water equivalent, non-hygroscopic, radiation tolerant scintillator material (designated HM: hybrid material) that is viewed by high frame rate CMOS cameras. Folded optics using mirrors enable a thin monitor profile of ∼10 cm. A field programmable gate array (FPGA) data acquisition system generates real-time analysis on a time scale appropriate to the FLASH RT beam modality: 100-1000 Hz for pulsed electrons and 10-20 kHz for quasi-continuous scanning proton pencil beams. An ion beam monitor served as the initial development platform for this work and was tested in low energy heavy-ion beams (86Kr+26 and protons). A prototype FBSM was fabricated and then tested in various radiation beams that included FLASH level dose per pulse electron beams, and a hospital RT clinic with electron beams. RESULTS: Results presented in this report include image quality, response linearity, radiation hardness, spatial resolution, and real-time data processing. The HM scintillator was found to be highly radiation damage resistant. It exhibited a small 0.025%/kGy signal decrease from a 216 kGy cumulative dose resulting from continuous exposure for 15 min at a FLASH compatible dose rate of 237 Gy/s. Measurements of the signal amplitude versus beam fluence demonstrate linear response of the FBSM at FLASH compatible dose rates of >40 Gy/s. Comparison with commercial Gafchromic film indicates that the FBSM produces a high resolution 2D beam image and can reproduce a nearly identical beam profile, including primary beam tails. The spatial resolution was measured at 35-40 µm. Tests of the firmware beta version show successful operation at 20 000 Hz frame rate or 50 µs/frame, where the real-time analysis of the beam parameters is achieved in less than 1 µs. CONCLUSIONS: The FBSM is designed to provide real-time beam profile monitoring over a large active area without significantly degrading the beam quality. A prototype device has been staged in particle beams at currents of single particles up to FLASH level dose rates, using both continuous ion beams and pulsed electron beams. Using a novel scintillator, beam profiling has been demonstrated for currents extending from single particles to 10 nA currents. Radiation damage is minimal and even under FLASH conditions would require ≥50 kGy of accumulated exposure in a single spot to result in a 1% decrease in signal output. Beam imaging is comparable to radiochromic films, and provides immediate images without hours of processing. Real-time data processing, taking less than 50 µs (combined data transfer and analysis times), has been implemented in firmware for 20 kHz frame rates for continuous proton beams.

Uncommon Detection of Leiomyoma in the Penile Corpus Spongiosum Using FDG PET/CT: A Case Report.

ABSTRACT: Primary tumors of the penile corpus spongiosum are rare. Hereby we describe the scintigraphic findings of a case of penile leiomyoma within the corpus spongiosum tissue, which was incidentally detected on FDG PET/CT. The benign neoplasm was growing in close proximity to the urethra showing increased focal FDG uptake on sequential PET/CT studies. Subsequently, the patient experienced obstructive urinary symptoms, and the tumor was resected. We concluded that the possibility of neoplasm should be kept in mind while evaluating a patient with persistent focal penile FDG uptake, which may be the first and only manifestation of the disease.

Heart Rate Variability as a Prognostic Tool for Gastroschisis Infants in the Neonatal Intensive Critical Unit.

OBJECTIVE: Gastroschisis is the most common congenital abdominal wall defect, with an increasing incidence. It results in extrusion of abdominal contents with associated delayed intestinal motility. Abnormal heart rate characteristics (HRCs) such as decreased variability occur due to the inflammatory response to sepsis in preterm infants. This study aimed to test the hypothesis that infants with gastroschisis have decreased heart rate variability (HRV) after birth and that this physiomarker may predict outcomes. STUDY DESIGN: We analyzed heart rate data from and clinical variables for all infants admitted with gastroschisis from 2009 to 2020. RESULTS: Forty-seven infants were admitted during the study period and had available data. Complex gastroschisis infants had reduced HRV after birth. For those with sepsis and necrotizing enterocolitis, abnormal HRCs occurred early in the course of illness. CONCLUSION: Decreased HRV was associated with complex gastroschisis. Infants in this group experienced complications that prolonged time to full enteral feeding and time on total parenteral nutrition. KEY POINTS: · Infants with gastroschisis can be classified into two subcategories, simple and complex disease.. · Those with complex disease often require prolonged stays in the neonatal intensive care unit and costly hospitalizations. We hypothesized that infants with complex gastroschisis are more likely to have abnormal HRC due to intestinal inflammation.. · In this study, we identified associations between abnormal HRV, heart rate characteristicHRC, and the development of gastroschisis complications. Additionally, we described differences in clinical characteristics between infants with complex versus simple gastroschisis..

A Prototype Scintillator Real-Time Beam Monitor for Ultra-high Dose Rate Radiotherapy.

Background: FLASH Radiotherapy (RT) is an emergent cancer radiotherapy modality where an entire therapeutic dose is delivered at more than 1000 times higher dose rate than conventional RT. For clinical trials to be conducted safely, a precise and fast beam monitor that can generate out-of-tolerance beam interrupts is required. This paper describes the overall concept and provides results from a prototype ultra-fast, scintillator-based beam monitor for both proton and electron beam FLASH applications. Purpose: A FLASH Beam Scintillator Monitor (FBSM) is being developed that employs a novel proprietary scintillator material. The FBSM has capabilities that conventional RT detector technologies are unable to simultaneously provide: 1) large area coverage; 2) a low mass profile; 3) a linear response over a broad dynamic range; 4) radiation hardness; 5) real-time analysis to provide an IEC-compliant fast beam-interrupt signal based on true two-dimensional beam imaging, radiation do-simetry and excellent spatial resolution. Methods: The FBSM uses a proprietary low mass, less than 0.5 mm water equivalent, non-hygroscopic, radiation tolerant scintillator material (designated HM: hybrid material) that is viewed by high frame rate CMOS cameras. Folded optics using mirrors enable a thin monitor profile of ~10 cm. A field programmable gate array (FPGA) data acquisition system (DAQ) generates real-time analysis on a time scale appropriate to the FLASH RT beam modality: 100-1000 Hz for pulsed electrons and 10-20 kHz for quasi-continuous scanning proton pencil beams. An ion beam monitor served as the initial development platform for this work and was tested in low energy heavy-ion beams (86Kr+26 and protons). A prototype FBSM was fabricated and then tested in various radiation beams that included FLASH level dose per pulse electron beams, and a hospital radiotherapy clinic with electron beams. Results: Results presented in this report include image quality, response linearity, radiation hardness, spatial resolution, and real-time data processing. The HM scintillator was found to be highly radiation damage resistant. It exhibited a small 0.025%/kGy signal decrease from a 216 kGy cumulative dose resulting from continuous exposure for 15 minutes at a FLASH compatible dose rate of 237 Gy/s. Measurements of the signal amplitude vs beam fluence demonstrate linear response of the FBSM at FLASH compatible dose rates of > 40 Gy/s. Comparison with commercial Gafchromic film indicates that the FBSM produces a high resolution 2D beam image and can reproduce a nearly identical beam profile, including primary beam tails. The spatial resolution was measured at 35-40 µm. Tests of the firmware beta version show successful operation at 20,000 Hz frame rate or 50 µs/frame, where the real-time analysis of the beam parameters is achieved in less than 1 µs. Conclusions: The FBSM is designed to provide real-time beam profile monitoring over a large active area without significantly degrading the beam quality. A prototype device has been staged in particle beams at currents of single particles up to FLASH level dose rates, using both continuous ion beams and pulsed electron beams. Using a novel scintillator, beam profiling has been demonstrated for currents extending from single particles to 10 nA currents. Radiation damage is minimal and even under FLASH conditions would require ≥ 50 kGy of accumulated exposure in a single spot to result in a 1% decrease in signal output. Beam imaging is comparable to radiochromic films, and provides immediate images without hours of processing. Real-time data processing, taking less than 50 µs (combined data transfer and analysis times), has been implemented in firmware for 20 kHz frame rates for continuous proton beams.

Esophageal motility in systemic sclerosis before and after autologous hematopoietic cell transplantation.

INTRODUCTION: Systemic sclerosis (SSc) is associated with esophageal dysmotility. Autologous hematopoietic cell transplantation (HCT) results in improvement of skin tightness and lung function. Whether esophageal motility improves after HCT is unknown. METHODS: Esophageal motility was studied using high-resolution esophageal manometry in 21 SSc patients before and at multiple time points after autologous HCT. Median posttransplant follow-up was 2 years (range, 6 months to 5 years). RESULTS: Prior to HCT, all 21 patients had abnormal motility-10 (48%) had unmeasurable and 11 (52%) had measurable peristalsis. Manometric diagnosis in the former 10 patients was "absent contractility" and in the latter 11 patients "ineffective esophageal motility (IEM)." After HCT, among the 10 patients with absent contractility, 9 continued to have absent contractility and one demonstrated weak measurable peristalsis. Of the 11 patients with IEM, 5 experienced SSc relapse, and 2 out of these 5 patients developed absent contractility. Among the 6 non-relapsed patients, 4 continued to have IEM, and 2 developed normal motility. CONCLUSIONS: HCT appears to have no beneficial effect on motility in patients with unmeasurable peristalsis. In patients with measurable peristalsis, HCT appears to stabilize and in some normalize motility, unless relapse occurs. Key Points • In patients with systemic sclerosis, esophageal dysmotility is a significant contributor to morbidity and so far, there has been no data describing the effects of hematopoietic cell transplantation on esophageal motility. • Our work demonstrated that in patients with systemic sclerosis and unmeasurable esophageal peristalsis prehematopoietic cell transplantation, there was no measurable beneficial effect of transplantation on esophageal motility. • In patients with systemic sclerosis and measurable peristalsis prehematopoietic cell transplantation, esophageal motility stabilized, except in relapsed patients.

How do drivers mitigate the effects of naturalistic visual complexity? : On attentional strategies and their implications under a change blindness protocol.

How do the limits of high-level visual processing affect human performance in naturalistic, dynamic settings of (multimodal) interaction where observers can draw on experience to strategically adapt attention to familiar forms of complexity? In this backdrop, we investigate change detection in a driving context to study attentional allocation aimed at overcoming environmental complexity and temporal load. Results indicate that visuospatial complexity substantially increases change blindness but also that participants effectively respond to this load by increasing their focus on safety-relevant events, by adjusting their driving, and by avoiding non-productive forms of attentional elaboration, thereby also controlling "looked-but-failed-to-see" errors. Furthermore, analyses of gaze patterns reveal that drivers occasionally, but effectively, limit attentional monitoring and lingering for irrelevant changes. Overall, the experimental outcomes reveal how drivers exhibit effective attentional compensation in highly complex situations. Our findings uncover implications for driving education and development of driving skill-testing methods, as well as for human-factors guided development of AI-based driving assistance systems.

Implementation of ultrasound and fast magnetic resonance imaging pathway reduces computed tomography utilization in children with suspected appendicitis.

PURPOSE: Computed tomography (CT) is still used in the imaging diagnosis of acute appendicitis in children at many hospitals. We implemented an ultrasound (US) and fast magnetic resonance imaging (MRI) pathway for suspected appendicitis at our institution with the goal of reducing radiation exposure in children. METHODS: All children (< 18 years old) who underwent appendectomy between January 2011 and July 2021 were reviewed. Data were collected on all imaging studies performed. In December 2015, we initiated an imaging pathway for suspected acute appendicitis. US was the initial imaging study, and a rapid protocol MRI was performed if US was equivocal. Those could not tolerate MRI underwent CT. We evaluated the difference in percentage of patients who underwent CT before and after pathway initiation. RESULTS: 554 patients who underwent appendectomy did not have prior imaging studies on presentation to our hospital and were included in analysis. After initiating the pathway, the use of abdominal US increased from 87% (220 of 254) to 97% (291 of 300, p < 0.0001) and the use of MRI increased by 100% (0 MRIs pre-protocol, 90 of 300 patients post-protocol, p < 0.0001). CT utilization decreased significantly from 32% (82 of 254) to 2% (6 of 300, p < 0.0001). CONCLUSION: Embracing a new US and rapid MRI pathway to evaluate pediatric patients with suspected acute appendicitis resulted in significant reduction in CT utilization and therefore radiation exposure.

When searching helps you see: Bridging the gap between incidental and intentional change detection.

Participants in incidental change detection studies often miss large changes to visually salient or conceptually relevant objects such as actor substitutions across video cuts, but there are competing explanations of why participants fail to detect these changes. According to an integrative processing account, object-based attention typically induces integrated representation and comparison processes sufficient to detect changes to that object. On this view, participants miss changes in incidental paradigms because those paradigms fail to elicit the level of attention necessary to trigger integrated representation and comparison processes. In contrast, a selective processing account posits that representation and comparison processes needed to detect changes do not occur by default, even for attended objects, but are only elicited in response to specific functional needs. In four experiments, we tested detection of actor substitutions when participants engaged in tasks that required actor identity processing but did not necessarily require the combination of processes necessary to detect changes. Change blindness for actor substitutions persisted when participants counted the number of actors in the video and sometimes persisted when participants were instructed to remember the substituted actor for later recall. Change blindness consistently diminished, however, when participants were shown the prechange actor before or during the video and instructed to search for that actor in the video. Our results refine the contrast between selective and integrative processing by specifying how task demands to create durable visual representations can remain independent of comparison processes, while search demands can induce integrative comparison processes in a naturalistic setting. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Incidental Detection of Dual Spinal Meningiomas on 68 Ga-DOTATATE PET/CT Masquerading as Metastatic Disease in a Patient With Pulmonary Carcinoid Tumor.

ABSTRACT: Simultaneous occurrence of multiple meningiomas of the spine appearing at different neuroaxial levels is extremely rare event. We present the scintigraphic findings of incidentally detected multiple meningiomas of the spine on 68 Ga-DOTATATE PET/CT during the evaluation of a patient with pulmonary carcinoid tumor. These scintigraphic findings could result in a "false-positive" interpretation by exhibiting highly increased uptake similar to that of metastases of neuroendocrine neoplasm. Nuclear medicine physicians should be aware of this potential pitfall in somatostatin receptor imaging to prevent misinterpretation.

In vivo metabolomics identifies CD38 as an emergent vulnerability in LKB1 -mutant lung cancer.

LKB1/STK11 is a serine/threonine kinase that plays a major role in controlling cell metabolism, resulting in potential therapeutic vulnerabilities in LKB1-mutant cancers. Here, we identify the NAD + degrading ectoenzyme, CD38, as a new target in LKB1-mutant NSCLC. Metabolic profiling of genetically engineered mouse models (GEMMs) revealed that LKB1 mutant lung cancers have a striking increase in ADP-ribose, a breakdown product of the critical redox co-factor, NAD + . Surprisingly, compared with other genetic subsets, murine and human LKB1-mutant NSCLC show marked overexpression of the NAD+-catabolizing ectoenzyme, CD38 on the surface of tumor cells. Loss of LKB1 or inactivation of Salt-Inducible Kinases (SIKs)-key downstream effectors of LKB1- induces CD38 transcription induction via a CREB binding site in the CD38 promoter. Treatment with the FDA-approved anti-CD38 antibody, daratumumab, inhibited growth of LKB1-mutant NSCLC xenografts. Together, these results reveal CD38 as a promising therapeutic target in patients with LKB1 mutant lung cancer. SIGNIFICANCE: Loss-of-function mutations in the LKB1 tumor suppressor of lung adenocarcinoma patients and are associated with resistance to current treatments. Our study identified CD38 as a potential therapeutic target that is highly overexpressed in this specific subtype of cancer, associated with a shift in NAD homeostasis.

Neoadjuvant Osimertinib Followed by Sequential Definitive Radiation Therapy and/or Surgery in Stage III Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer: An Open-Label, Single-Arm, Phase 2 Study.

PURPOSE: The treatment for unresectable, locally advanced stage III non-small cell lung cancer (NSCLC) is concurrent chemoradiation therapy (CRT) followed by consolidation durvalumab. This study aimed to evaluate the benefit of neoadjuvant osimertinib as an alternative therapy to this approach with the aim of reducing the radiation field. METHODS AND MATERIALS: This investigation was a nonrandomized, open-label, single-arm, phase 2, prospective, proof-of-concept study. Eligible patients were classified as having treatment-naïve, nonoperable, stage III epidermal growth factor receptor-mutant NSCLC. Patients received 80 mg of oral osimertinib daily for 12 weeks before definitive radiation therapy (RT) and/or surgery. The response was assessed at weeks 6 and 12. For responders, sequential definitive RT and/or surgery were planned. Nonresponders were started on standard CRT. After RT ± surgery or CRT, patients were followed for 2 years without adjuvant therapy. The primary endpoint was the objective response rate (ORR), with September 20, 2022, set as the cut-off for data collection. Secondary endpoints were safety and the gross tumor volume (GTV), planned tumor volume (PTV), and the percentage of total lung volume minus GTV exceeding 20 Gy (V20%) before versus after osimertinib. Exploratory analyses included assessments of the presence of plasma circulating tumor-free DNA (ctDNA) before osimertinib treatment, at weeks 6 and 12, at the end of RT, and 6 weeks post-RT. RESULTS: Twenty-four patients were included (19 women; median age, 73 years; range, 51-82 years). Nineteen of 24 had never smoked, 20 of 24 had adenocarcinoma, 16 of 24 had exon 19 deletions, and 8 of 24 had exon 21 mutations. Participants had stage IIIA (10), IIIB (9), or IIIC (5) disease. Three patients were excluded from the analysis (1 dropped out and 2 were still undergoing osimertinib treatment at the cut-off date). The ORR to induction osimertinib was 95.2% (17 partial response, 3 complete response, and 1 progressive disease). After induction osimertinib, 13 of 20 patients were definitively radiated, 3 of 20 underwent surgery, and 5 of 20 were excluded. Four patients were restaged as stage IV (contralateral ground-glass opacities responded to osimertinib), and 1 patient withdrew informed consent. Three patients underwent surgery, one of whom was treated with RT. Two patients achieved pT1aN0, and one achieved pathologic complete response. The median GTV, PTV, and V20% before osimertinib treatment were 47.4 ± 76.9 cm3 (13.5-234.9), 227.0 ± 258.8 cm3 (77.8-929.2), and 27.1 ± 16.4% (6.2-60.3), respectively. The values after osimertinib treatment were 27.5 ± 42.3 cm3 (2.99-137.7; -48 ± 20%; P = .02), 181.9 ±198.4 cm3 (54-718.1; -31 ± 20%; P = .01), and 21.8 ± 11.7% (9.1-44.15; -24 ± 40%; P = .04), respectively. PTV/GTV/V20% reduction was associated with tumor size and central location. The median follow-up time was 28.71 months (range, 0.4-45.1 months), and median disease-free survival was not reached (mean, 30.59; standard error, 3.94; 95% confidence interval, 22.86-38.31). ctDNA was detected in 5 patients; 4 of 5 were positive for ctDNA at baseline and became negative during osimertinib induction but were again positive after osimertinib treatment was terminated. Interestingly, 3 patients who were ctDNA negative at baseline became weakly positive after RT and then were negative at follow-up. No significant adverse events were reported during the osimertinib or radiation phases. CONCLUSIONS: Neoadjuvant osimertinib therapy is feasible in patients with stage III lung cancer NSCLC, followed by definitive radiation and/or surgery, with an ORR of 95.2% and an excellent safety profile. Osimertinib induction for 12 weeks before definitive radiation (chemo-free) significantly reduced the radiation field by nearly 50% with a linear association with tumor size. Further studies are needed to test this chemo-free approach for long-term outcomes before practices are changed.

Histone Deacetylase 6 Inhibition Exploits Selective Metabolic Vulnerabilities in LKB1 Mutant, KRAS Driven NSCLC.

INTRODUCTION: In KRAS-mutant NSCLC, co-occurring alterations in LKB1 confer a negative prognosis compared with other mutations such as TP53. LKB1 is a tumor suppressor that coordinates several signaling pathways in response to energetic stress. Our recent work on pharmacologic and genetic inhibition of histone deacetylase 6 (HDAC6) revealed the impaired activity of numerous enzymes involved in glycolysis. On the basis of these previous findings, we explored the therapeutic window for HDAC6 inhibition in metabolically-active KRAS-mutant lung tumors. METHODS: Using cell lines derived from mouse autochthonous tumors bearing the KRAS/LKB1 (KL) and KRAS/TP53 mutant genotypes to control for confounding germline and somatic mutations in human models, we characterize the metabolic phenotypes at baseline and in response to HDAC6 inhibition. The impact of HDAC6 inhibition was measured on cancer cell growth in vitro and on tumor growth in vivo. RESULTS: Surprisingly, KL-mutant cells revealed reduced levels of redox-sensitive cofactors at baseline. This is associated with increased sensitivity to pharmacologic HDAC6 inhibition with ACY-1215 and blunted ability to increase compensatory metabolism and buffer oxidative stress. Seeking synergistic metabolic combination treatments, we found enhanced cell killing and antitumor efficacy with glutaminase inhibition in KL lung cancer models in vitro and in vivo. CONCLUSIONS: Exploring the differential metabolism of KL and KRAS/TP53-mutant NSCLC, we identified decreased metabolic reserve in KL-mutant tumors. HDAC6 inhibition exploited a therapeutic window in KL NSCLC on the basis of a diminished ability to compensate for impaired glycolysis, nominating a novel strategy for the treatment of KRAS-mutant NSCLC with co-occurring LKB1 mutations.

Using memes to promote student engagement and classroom community during remote learning.

As colleges moved to online teaching during the COVID-19 pandemic, many instructors found it difficult to maintain student engagement and classroom community in the virtual environment. We developed a semester-long activity for a molecular biology research methodology course where students created, and shared original memes related to course content with peers through group chat. Surveys and semi-structured interviews revealed that the exercise was effective in promoting student engagement, a sense of community, and relieving stress.

Hematopoietic Cell Transplantation for Systemic Sclerosis-A Review.

Systemic sclerosis (SSc) is an autoimmune, multi-organ, connective tissue disease associated with significant morbidity and mortality. Conventional immunosuppressive therapies demonstrate limited efficacy. Autologous hematopoietic stem cell transplantation (HCT) is more efficacious but carries associated risks, including treatment-related mortality. Here, we review HCT as a treatment for SSc, its efficacy and toxicity in comparison to conventional therapies, and the proposed mechanisms of action. Furthermore, we discuss the importance of and recent developments in patient selection. Finally, we highlight the knowledge gaps and future work required to further improve patient outcomes.

Video speeding can be efficient and speeding-induced preference cost can be lessened by selective speeding.

Over the past decade, screen-captured instructional videos have become popular tools for learning. Viewers wanting to learn efficiently can play these videos at faster-than-normal speeds, a feature offered by hosting services such as YouTube. Although previous research suggests that moderate speeding may not lessen learning, little research has tested this form of media for speeding-induced learning impairments. Further, even if learning is not impaired by speeding, the degree to which users find speed increases taxing and/or unpleasant is unknown. We therefore created a set of screen-captured instructional videos and tested whether speeding them by up to 250% affected learning, perceived workload, and preferences. Speed increases of up to 200% minimally affected learning, but even modest 150% speed increases substantially increased perceived workload and reduced viewer preferences. However, we were able to create videos that were more selectively speeded by concentrating speeding on pauses and relatively unimportant and slow speech. These videos were just as time efficient as the 150% speeded videos, but viewers preferred them. Our findings demonstrate that speeded instructional videos have the potential to facilitate efficient learning, and they suggest techniques such as selective speeding that may be used to support efficiency while lessening viewer preference costs. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Standing Intravenous Acetaminophen Is Associated With a Reduction of Post-operative Opioid Use in Infants Aged Less Than 1 Year Treated on the Acute Care Floor.

INTRODUCTION: Given the negative clinical effects opiates can have, the search for alternative forms of analgesia to treat post-operative pain continues. We implemented an opiate reduction strategy using standing intravenous (IV) acetaminophen for infants aged less than 1 y who underwent abdominal or anorectal surgery and recovered on the acute care floor. MATERIALS AND METHODS: Infants were administered standing IV acetaminophen every 6 h for a minimum of 48 h as the main form of post-operative analgesia. Pain severity was objectively scored using the Face, Legs, Activity, Cry, and Consolability (FLACC) scale. A before-and-after retrospective cohort analysis was performed and process control charts were used to examine trends in post-operative opiate use in our pre-intervention (January 2012 to January 2016), roll-out (January 2016 to December 2016), and post-intervention (December 2016 to December 2020) cohorts. RESULTS: A total of 131 infants were included: 56 in the pre-intervention, 17 in the roll-out, and 58 in the post-intervention group. Patient demographics were equivalent. The intervention was associated with a 36-fold reduction in post-operative morphine equivalents (median 0.36 mg/kg in the pre-intervention group versus 0.0 mg/kg in the post-intervention group, P < 0.0001). The median and maximum FLACC pain scores along with clinical safety profiles were statistically equivalent between the groups. The intervention was associated with a 2-d reduction in post-operative length of stay (P < 0.0001). CONCLUSIONS: Standing IV acetaminophen is associated with a reduction of post-operative opioid use in infants being treated on the acute care floor while maintaining equivalent FLACC pain scores. Similar opiate reduction strategies may be of value at other institutions.

Radioiodine Uptake in Incidentally Detected Neuroendocrine Tumor: Correlative Imaging With FDG PET/CT and 68 Ga-DOTATATE PET/CT.

ABSTRACT: Radioiodine whole-body scintigraphy has long been used for detection of differentiated thyroid carcinoma with high avidity in functioning thyroid tissues. However, uptake is not completely specific, and "false-positive" uptake in nonthyroidal tumors have rarely been reported. Herein, we present a case of incidentally detected neuroendocrine tumor showing high radioiodine uptake initially suspected to be thyroid metastasis. Correlative imaging with FDG PET/CT and 68 Ga-DOTATATE PET/CT is presented, and literature survey is discussed. We conclude that neuroendocrine tumor should be added to the reported list of neoplasms that can show "false-positive" uptake representing a potential interpretative pitfall.