Single-cell decoding of drug induced transcriptomic reprogramming in triple negative breast cancers.

BACKGROUND: The encoding of cell intrinsic drug resistance states in breast cancer reflects the contributions of genomic and non-genomic variations and requires accurate estimation of clonal fitness from co-measurement of transcriptomic and genomic data. Somatic copy number (CN) variation is the dominant mutational mechanism leading to transcriptional variation and notably contributes to platinum chemotherapy resistance cell states. Here, we deploy time series measurements of triple negative breast cancer (TNBC) single-cell transcriptomes, along with co-measured single-cell CN fitness, identifying genomic and transcriptomic mechanisms in drug-associated transcriptional cell states. RESULTS: We present scRNA-seq data (53,641 filtered cells) from serial passaging TNBC patient-derived xenograft (PDX) experiments spanning 2.5 years, matched with genomic single-cell CN data from the same samples. Our findings reveal distinct clonal responses within TNBC tumors exposed to platinum. Clones with high drug fitness undergo clonal sweeps and show subtle transcriptional reversion, while those with weak fitness exhibit dynamic transcription upon drug withdrawal. Pathway analysis highlights convergence on epithelial-mesenchymal transition and cytokine signaling, associated with resistance. Furthermore, pseudotime analysis demonstrates hysteresis in transcriptional reversion, indicating generation of new intermediate transcriptional states upon platinum exposure. CONCLUSIONS: Within a polyclonal tumor, clones with strong genotype-associated fitness under platinum remained fixed, minimizing transcriptional reversion upon drug withdrawal. Conversely, clones with weaker fitness display non-genomic transcriptional plasticity. This suggests CN-associated and CN-independent transcriptional states could both contribute to platinum resistance. The dominance of genomic or non-genomic mechanisms within polyclonal tumors has implications for drug sensitivity, restoration, and re-treatment strategies.

Hybrid Versus Conventional Colorectal Endoscopic Submucosal Dissection: A Multicenter Randomized Controlled Trial (Short-Endoscopic Submucosal Dissection).

INTRODUCTION: Hybrid endoscopic submucosal dissection (H-ESD), which utilizes ESD knife along with snare-based resection, has been developed to overcome the technical complexity of conventional ESD (C-ESD). The aim of this study was to compare the therapeutic outcomes of H-ESD vs C-ESD for nonpedunculated colorectal lesions ≥20 mm in size. METHODS: We conducted a multicenter randomized controlled trial to compare H-ESD and C-ESD (Short-ESD trial). Patients with colorectal lesions between 20 and 50 mm in size were randomly assigned (1:1) to H-ESD or C-ESD. Primary outcome was procedure time/speed. Secondary outcomes were en bloc and complete (R0) resection rates and adverse event rates. RESULTS: A total of 89 patients (median age 63 years; 49.3% women) with the median polyp size of 30 mm underwent H-ESD (n = 40) and C-ESD (n = 49). The mean procedure time of H-ESD was significantly shorter than that of C-ESD (41.1 ± 16.3 vs 54.3 ± 28.2 minutes; P = 0.007). The en bloc and R0 resection rates trended lower in the H-ESD vs C-ESD groups (77.5% vs 87.8%; P = 0.26% and 72.5% vs 79.6%; P = 0.46) without reaching statistical significance. Adverse event rate was similar between H-ESD and C-ESD (10% vs 8.2%; P = 1.00). DISCUSSION: Both H-ESD and C-ESD were safe and effective for resection of large colorectal lesions. H-ESD was associated with a shorter procedure time. H-ESD may represent a viable alternative to C-ESD, with the main advantage being easy applicability of a snare-based technique for colorectal lesions. Future studies are needed to further define the most suitable lesions for H-ESD, as to optimize efficiency and safety without compromising resection outcomes. ClinicaTrials.gov NCT NCT05347446.

Addressing OSH challenges in non-standardized work practices in small-scale FMCG units by introducing context-specific ergonomic pouch/sachet cutting apparatus.

BACKGROUND: The FMCG manufacturing industry in industrially developing countries operates in a manual or semi-automatic setup, employing a vast labor force. Several non-standardized work activities prevail on the FMCG shop floor and remain prone to safety-related risks involving repetitive motions, forceful exertions, and awkward postures. Among those, the rework of defective pouches/sachets is an unsafe activity of prime concern. It is prone to minor nicks, cuts, and injuries due to inadequate tools being used. It involves sharp cutters/blades and extensive forceful manual hand squeezing, which leads to drudgery and safety concerns. There lies the lack of standardized tools/apparatus for rework activity, and efforts towards its mitigation are required. OBJECTIVE: Current research aims to address occupational safety-related issues in non-standardized rework activity in small-scale FMCG units through an innovative product design approach. METHODS: An ergo-audit was conducted in eight small-scale FMCG units to identify the prevailing ergonomic stressors and safety concerns. The most critical area of concern, i.e., rework activity, was chosen through card-sorting sessions and discussions held with the stakeholders. An appropriate context-specific apparatus was designed/developed to ensure better safety and occupational health utilizing a systematic product design method involving three phases: initial field survey, design and development, and field trials. RESULTS: The apparatus, which was developed and factory-trialed, was evaluated for productivity improvement and ensuring user compatibility from various human factors' perspectives. CONCLUSION: In field trials, the developed apparatus was found effective in mitigating safety concerns and various ergonomic stressors associated with FMCG rework.

COVID-19 Predictors of Morbidity and Mortality.

Background and objectives There are multiple factors and comorbid conditions that can impact the outcomes of COVID-19. This study aimed to assess how patients with certain comorbidities and risk factors were affected by COVID-19. Methodology This retrospective study involved 578 inpatients who presented to the emergency room (ER) due to COVID-19 infection, diagnosed with COVID-19 between 2020 and 2021. This research takes note of COVID-19 severity, particularly in individuals with comorbidities such as chronic obstructive pulmonary disease (COPD), diabetes mellitus (DM), chronic kidney disease (CKD), coronary artery disease (CAD), and hypertension. Results A two-sample t-test found that age was a significant factor affecting hospital length of stay (LOS) and mortality. An ANOVA analysis of race, DM, and CAD showed a significant effect on LOS (p-values = 0.005, 0.01, and 0.01, respectively) but not on mortality and intubation. White patients had an increased LOS compared to other ethnicities. CKD and hypertension significantly affect mortality and LOS. However, COPD did significantly influence all three variables: mortality, intubation, and LOS (p-values = 0.005, 0.013, and 0.01, respectively). A multiple ANOVA test showed that COPD, hypertension, and CKD had a significant effect on mortality, intubation, and LOS (p-values = 0.014, 0.004, and 0.01, respectively). DM showed weaker significance on mortality, intubation, and LOS (p-value = 0.108). Conclusions Patients with all three comorbid conditions (COPD, hypertension, and CKD) had increased length of stay, intubation, and mortality; thus, appropriate measures including close observation and early intervention may be necessary to prevent mortality in these patients.

Gut Microbiota Profiles in Myopes and Nonmyopes.

Purpose: To identify compositional differences in the gut microbiome of nonmyopes (NM) and myopes using 16S ribosomal RNA sequencing and to investigate whether the microbiome may contribute to the onset or progression of the condition. Methods: Faecal samples were collected from 52 adult participants, of whom 23 were NM, 8 were progressive myopes (PM), and 21 were stable myopes (SM). The composition of the gut microbiota in each group was analysed using 16S ribosomal RNA gene sequencing. Results: There were no significant differences in alpha and beta diversity between the three groups (NM, PM, and SM). However, the distributions of Bifidobacterium, Bacteroides, Megamonas, Faecalibacterium, Coprococcus, Dorea, Roseburia, and Blautia were significantly higher in the myopes (SM and PM combined) when compared with emmetropes. The myopes exhibited significantly greater abundance of bacteria that are linked to the regulation of dopaminergic signalling, such as Clostridium, Ruminococcus, Bifidobacterium, and Bacteroides. Individuals with stable myopia were found to have a significantly higher proportion of Prevotella copri than those with progressive myopia. Bifidobacterium adolescentis, a gamma-aminobutyric acid (GABA)-producing bacterium, was significantly higher in all myopes than in NM and, in the comparison between SM and PM, it is significantly higher in SM. B. uniformis and B. fragilis, both GABA-producing Bacteroides, were present in relatively high abundance in all myopes and in SM compared with PM, respectively. Conclusions: The presence of bacteria related to dopamine effect and GABA-producing bacteria in the gut microbiome of myopes may suggest a role of these microorganisms in the onset and progression of myopia.

Facile Layer Diffusion Technique for Synthesis of Terbium-Based Metal Organic Framework for Fluorometric Sensing of Hydroquinone.

A photoluminescent terbium (III)-based Metal Organic Framework (MOF) was synthesized at room temperature by layer diffusion method utilizing mixed carboxylate linkers (4,4'-oxybis(benzoic acid) and benzene-1,3,5 tricarboxylic acid). Synthesized MOF has crystalline nature and rod-shaped morphology and is thermally stable up to 455 °C. The fluorescence emission spectra and theoretical results revealed that carboxylate linkers functioned as sensitizers for Tb(III) photoluminescence which resulted in four distinct emission peaks at 495, 547, 584, and 621 nm corresponding to the transitions 5D4 → 7F6, 5D4 → 7F5, 5D4 → 7F4, and 5D4 → 7F3. Using synthesized MOF as fluorescent probe, hydroquinone was detected in aqueous medium with a detection limit of 0.048 µM, remarkable recovery (95.6-101.1%), and relative standard deviation less than 2.25%. The quenching phenomenon may be ascribed to electron transfer from synthesized probe to oxidized hydroquinone via carboxylic groups on the surface of MOF, which is further supported by photo-induced electron transfer mechanism. This study introduces a cheaper, faster, and more accurate method for hydroquinone detection.

Quantification of interstitial cells of Cajal and fibrosis during gastric per-oral endoscopic myotomy and its association with clinical outcomes.

Background and study aims Alterations to interstitial cells of Cajal (ICC) and collagen fibrosis have been implicated in the pathogenesis of gastroparesis. We aimed to evaluate the feasibility and safety of pyloric muscle sampling during gastric peroral endoscopic myotomy (G-POEM) and the association between pyloric ICC density and degree of fibrosis with clinical outcomes. Patients and methods This was a single-center prospective study of gastroparetic patients who underwent G-POEM and intraprocedural pyloric muscle biopsies between January 2022 and April 2023. ICC count was estimated using CD117 stain and trichome for collagen fibrosis. Clinical response to G-POEM was defined as an improvement of ≥ 1 point on the Gastroparesis Cardinal Symptom Index. Results Fifty-six patients (median age 60 years, 71.4% women) underwent G-POEM (100% technical success; 71.4% clinical response). ICC depletion (< 10/high-power field) and fibrosis were encountered in 70.4% and 75% of the cases, respectively. There was no difference in mean ICC count between G-POEM responders vs. non-responders (7±3.6 vs. 7.7±3.3; P = 0.9). There was no association between ICC density or degree of fibrosis with the etiology of gastroparesis, duration of symptoms, gastric emptying rate, or pyloric impedance planimetry. Patients who did not respond to G-POEM had a significantly higher degree of moderate/severe fibrosis when compared with those who responded (81.3% vs. 25%; P = 0.0002). Conclusions Pyloric muscle biopsies during G-POEM was feasible and safe. ICC depletion and pyloric muscle fibrosis are common in gastroparetic patients. The degree of fibrosis may be related to pyloric dysfunction and clinical response to G-POEM. Additional studies are needed to confirm these results.

Reduced Protein Stability of 11 Pathogenic Missense STXBP1/MUNC18-1 Variants and Improved Disease Prediction.

BACKGROUND: Pathogenic variants in STXBP1/MUNC18-1 cause severe encephalopathies that are among the most common in genetic neurodevelopmental disorders. Different molecular disease mechanisms have been proposed, and pathogenicity prediction is limited. In this study, we aimed to define a generalized disease concept for STXBP1-related disorders and improve prediction. METHODS: A cohort of 11 disease-associated and 5 neutral variants (detected in healthy individuals) were tested in 3 cell-free assays and in heterologous cells and primary neurons. Protein aggregation was tested using gel filtration and Triton X-100 insolubility. PRESR (predicting STXBP1-related disorder), a machine learning algorithm that uses both sequence- and 3-dimensional structure-based features, was developed to improve pathogenicity prediction using 231 known disease-associated variants and comparison to our experimental data. RESULTS: Disease-associated variants, but none of the neutral variants, produced reduced protein levels. Cell-free assays demonstrated directly that disease-associated variants have reduced thermostability, with most variants denaturing around body temperature. In addition, most disease-associated variants impaired SNARE-mediated membrane fusion in a reconstituted assay. Aggregation/insolubility was observed for none of the variants in vitro or in neurons. PRESR outperformed existing tools substantially: Matthews correlation coefficient = 0.71 versus <0.55. CONCLUSIONS: These data establish intrinsic protein instability as the generalizable, primary cause for STXBP1-related disorders and show that protein-specific ortholog and 3-dimensional information improve disease prediction. PRESR is a publicly available diagnostic tool.

Triply Selective & Sequential Diversification at Csp 3: Expansion of Alkyl Germane Reactivity for C-C & C-Heteroatom Bond Formation.

We report the triply selective and sequential diversification of a single Csp 3 carbon carrying Cl, Bpin and GeEt3 for the modular and programmable construction of sp3-rich molecules. Various functionalizations of Csp 3-Cl and Csp 3-BPin (e.g. alkylation, arylation, homologation, amination, hydroxylation) were tolerated by the Csp 3-GeEt3 group. Moreover, the methodological repertoire of alkyl germane functionalization was significantly expanded beyond the hitherto known Giese addition and arylation to alkynylation, alkenylation, cyanation, halogenation, azidation, C-S bond formation as well as the first demonstration of stereo-selective functionalization of a Csp 3-[Ge] bond.

Consumption of the Non-Nutritive Sweetener Stevia for 12 Weeks Does Not Alter the Composition of the Human Gut Microbiota.

The use of non-nutritive sweeteners (NNSs) as an alternative to caloric sugars has increased in recent years. Stevia is an NNS that has demonstrated beneficial effects on appetite and energy intake. However, the impact on the gut microbiota is not well understood. Therefore, we investigated how regular consumption of stevia, for up to 12 weeks, impacts the human gut microbiota. Healthy subjects with a normal body mass index participated in our study; the stevia group (n = 14) was asked to consume five drops of stevia twice daily, compared to control participants (n = 13). Faecal samples collected before and after treatment were analysed by 16S rRNA gene sequencing. Stevia did not cause significant changes in the alpha or beta diversity when compared to the control groups. When the relative abundances of taxa were investigated, no clear differences were detected. Conversely, a random forest analysis correctly associated the gut microbiome with the control and stevia groups with an average of 75% accuracy, suggesting that there are intrinsic patterns that could discriminate between control and stevia use. However, large-scale changes in the gut microbiota were not apparent in this study, and, therefore, our data suggest that stevia does not significantly impact the gut microbiota.

Pure and Antimony-doped Tin Oxide Nanoparticles for Fluorescence Sensing and Dye Degradation Applications.

Luminescent antimony doped tin oxide nanoparticles have drawn tremendous attention from researchers due to its low cost, chemical inertness and stability. Herein, a quick, facile and economic hydrothermal/solvothermal method was utilized for the preparation of antimony doped (1%, 3%, 5%, 7% and 10%) tin oxide nanoparticles. The antimony doping in a reasonable range can change the properties of SnO2. As such, a lattice distortion increases with increase in doping, which is evidenced through crystallographic studies. It was found that the highest photocatalytic degradation efficiency of malachite green (MG) dye of about 80.86% was achieved with 10% Sb-doped SnO2 in aqueous media due to small particle size. Moreover, 10% Sb-doped SnO2 also showed the highest fluorescence quenching efficiency of about 27% for Cd2+ of concentration 0.11 µg/ml in the drinking water. The limit of detection (LOD) comes out as 0.0152 µg/ml. This sample selectively detected the cadmium ion even in the presence of other heavy metal ions. Notably, 10% Sb-doped SnO2 could appeared as a promising sensor for fast analysis of Cd2+ ions in real samples.

Refractory Thyroid Eye Disease Unresponsive to Teprotumumab: A Case Report.

Thyroid eye disease (TED) is a complex autoimmune condition that can cause proptosis, ophthalmoplegia, diplopia, optic nerve compression, and vision loss. These clinical findings are caused by a complex pathological mechanism characterized by thyroid-stimulating hormone receptor autoantibodies activating thyroid-stimulating hormone receptors (TSH-Rs). Overexpressed insulin-like growth factor 1 (IGF-1) receptors found in orbital fibroblasts form complexes with these TSH-Rs, leading to the inflammation and expansion of these tissues. Teprotumumab, a human monoclonal antibody sold under the brand name Tepezza, is currently the only FDA-approved immunotherapy for the treatment of TED. Given as an intravenous infusion every three weeks, teprotumumab works by suppressing IGF-1 receptors, thereby interfering with TSH-R and IGF-1 complex-mediated actions in these fibroblasts. The efficacy of teprotumumab was established in randomized, placebo-controlled clinical trials, which demonstrated clinically meaningful improvements in proptosis, inflammation, and diplopia. While teprotumumab has been shown to be efficacious, our patient with TSHRAb-positive euthyroid thyroid-associated ophthalmopathy who presented with diplopia did not have any significant improvement following the standard treatment dose of eight infusions over a 24-week period. This case underscores not only barriers to treatment, such as the high cost of teprotumumab but also highlights the importance of identifying risks for nonresponse.

Diagnostic Accuracy of the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC): An Institution Experience.

The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is a standardized system which is used to classify results of thyroid fine-needle aspiration (FNA). This system is used to evaluate and determine which patients should get thyroid surgery. It was created in order to reduce the number of patients requiring surgery. The question remains as to whether this reporting system is accurate in determining those nodules that have malignant potential and those that do not. This study is a retrospective analysis of patients in one institution who have undergone FNA and then thyroid surgery based on TBSRTC. The outcome of the pathology reports after surgery was analyzed to determine the accuracy of TBSRTC in our institution (Lourdes Hospital, Binghamton, NY). The results from our institution were compared with similar studies in other institutions to determine accuracy and reproducibility. Our results indicated that the risk of malignancy in each Bethesda category was similar to the risk percentages described for most categories in the 2017 TBSRTC update.

Breaking the error chain with SEE: cascade analysis of endodontic errors in clinical training.

The ongoing endeavors to uncover the link between the prevalent errors in clinical endodontic training and undergraduate education are founded on tentative assumptions. This investigation was aimed at determining if cascade analysis can provide an understanding of the origins and causes of errors and if the sensitivity of student reports to the impact of errors on treatment outcomes can be established.In 2021, a group of investigators from the endodontics department concerned with clinical dental education launched the Study of Endodontic Errors (SEE). Sixty-six undergraduate dental students at one dental teaching hospital submitted anonymous narratives of problems they witnessed in their root canal treatment practices. The reports were examined to determine the sequence of events and the major errors. We kept track of the consequences of treatment outcomes, both as reported by students and as deduced by investigators.In 77% of the narratives, a chain of errors was recorded. The majority of the errors that took place were related to the working length or width of root canals. A substantial portion, 86%, of these errors could have been prevented through a deeper comprehension of the concepts that underlie working length and width. 75% of the errors that initiated cascades involved losing the correct working length. When asked whether the treatment outcome was compromised, students answered affirmatively in 16% of cases in which their narratives described compromised outcomes. Unacceptable outcomes necessitating re-treatment accounted for only 3% of student-reported consequences, but when investigator-inferred consequences were considered, the percentage more than doubled (7%).Cascade analysis of student error narratives is useful in understanding the triggering chain of events, but students provide insufficient information about how treatment outcomes are affected. Misconceptions about working length and width appear to play a significant role in the propagation of procedural errors.

Altered Oral Nitrate Reduction and Bacterial Profiles in Hypertensive Women Predict Blood Pressure Lowering Following Acute Dietary Nitrate Supplementation.

BACKGROUND: The efficacy of dietary nitrate supplementation to lower blood pressure (BP) in pregnant women is highly variable. We aimed to investigate whether differences in oral microbiota profiles and oral nitrate-reducing capacity may explain interindividual differences in BP lowering following nitrate supplementation. METHODS: Participants recruited for this study were both pregnant and nonpregnant women, with or without hypertension (n=55). Following an overnight fast, plasma, saliva, and tongue scraping samples were collected for measurement of nitrate/nitrite concentrations, oral NaR (nitrate reductase) activity, and microbiota profiling using 16S rRNA gene sequencing. Baseline BP was measured, followed by the administration of a single dose of dietary nitrate (400 mg nitrate in 70 mL beetroot juice). Post-nitrate intervention, plasma and salivary nitrate/nitrite concentrations and BP were determined 2.5 hours later. RESULTS: Women with hypertension had significantly lower salivary nitrite concentrations (P=0.006) and reduced abundance of the nitrate-reducing taxa Veillonella(P=0.007) compared with normotensive women. Oral NaR activity was not significantly different in pregnant versus nonpregnant women (P=0.991) but tended to be lower in hypertensive compared with normotensive women (P=0.099). Oral NaR activity was associated with both baseline diastolic BP (P=0.050) and change in diastolic BP following acute nitrate intake (P=0.01, adjusted for baseline BP). CONCLUSIONS: The abundance and activity of oral nitrate-reducing bacteria impact both baseline BP as well as the ability of dietary nitrate supplementation to lower BP. Strategies to increase oral nitrate-reducing capacity could lower BP and enhance the efficacy of dietary nitrate supplementation, in pregnancy as well as in nonpregnant adults. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03930693.

Terbium-based dual-ligand metal organic framework by diffusion method for selective and sensitive detection of danofloxacin in aqueous medium.

A water-dispersible Tb(III)-based metal organic framework (TBP) was produced by diffusion technique using benzene-1,3,5-tricarboxylic acid (BTC) and pyridine as easily accessible ligands at low cost. The as-synthesized TBP with a crystalline structure and rod-shaped morphology has exhibited thermal stability up to 465 °C. Elemental analysis confirmed the presence of carbon, oxygen, nitrogen, and terbium in the synthesized MOF. TBP was used as a fluorescent probe for detection of danofloxacin (DANO) in an aqueous medium with significant enhancement of fluorescence intensity as compared to various fluoroquinolone antibiotics (levofloxacin (LEVO), ofloxacin (OFLO), norfloxacin (NOR), and ciprofloxacin (CIPRO)) with a low detection limit of 0.45 ng/mL (1.25 nm). The developed method has successfully detected DANO rapidly (i.e., response time = 1 min) with remarkable recovery (97.66-101.96%) and a relative standard deviation (RSD) of less than 2.2%. Additionally, TBP showcased good reusability up to three cycles without any significant performance decline. The in-depth mechanistic studies of the density functional theory (DFT) calculations and mode of action revealed that hydrogen bonding interactions and photo-induced electron transfer (PET) are the major factors for the turn-on enhancement behavior of TBP towards DANO. Thus, the present work provides the quick and precise identification of DANO using a new fluorescent MOF (TBP) synthesized via a unique and facile diffusion technique.

Efficient Turn-On Zr Based Metal Organic Framework Fluorescent Sensor for Ultrafast Detection of Danofloxacin in Milk Samples.

Metal organic framework, UiO-67 was synthesized by coordinating Zr(IV) with 4,4'-biphenyldicarboxylic acid (BPDC) ligand. Morphology and crystallinity of MOF was confirmed with FE-SEM and PXRD procedure. Danofloxacin (DANO), a veterinary fluoroquinolone antibiotic, was detected in milk by employing UiO-67 as "turn-on" fluorescent sensor. Original photoluminescent (PL) efficiency of UiO-67 sensor was enhanced on its electronic interaction with DANO molecule. Significant PL efficiency enhancement, lower detection limit 0.49 ng/mL (1.37 nM), swift detection (time < 1 min), and excellent linear correlation (R2 = 0.9988) indicated extraordinary sensitivity of developed UiO-67 sensor for DANO. Selectivity and performance of sensor was unaltered in presence of interfering species and detection results were obtained under permissible variation limits. Method applied successfully for ultra-trace detection of DANO residues in milk samples.

A MYCN-independent mechanism mediating secretome reprogramming and metastasis in MYCN-amplified neuroblastoma.

MYCN amplification (MNA) is a defining feature of high-risk neuroblastoma (NB) and predicts poor prognosis. However, whether genes within or in close proximity to the MYCN amplicon also contribute to MNA+ NB remains poorly understood. Here, we identify that GREB1, a transcription factor encoding gene neighboring the MYCN locus, is frequently coexpressed with MYCN and promotes cell survival in MNA+ NB. GREB1 controls gene expression independently of MYCN, among which we uncover myosin 1B (MYO1B) as being highly expressed in MNA+ NB and, using a chick chorioallantoic membrane (CAM) model, as a crucial regulator of invasion and metastasis. Global secretome and proteome profiling further delineates MYO1B in regulating secretome reprogramming in MNA+ NB cells, and the cytokine MIF as an important pro-invasive and pro-metastatic mediator of MYO1B activity. Together, we have identified a putative GREB1-MYO1B-MIF axis as an unconventional mechanism promoting aggressive behavior in MNA+ NB and independently of MYCN.

Classification and Locoregional Treatment of Rectal Neuroendocrine Tumors.

A 43-year-old male presented to his primary care physician's office with a complaint of painless rectal bleeding with a concomitant weight loss of 10-15 pounds and intermittent abdominal pain. Endoscopic evaluation was remarkable for a 5 mm rectal polyp roughly 10 cm from the anal verge. Resection was performed and the pathology was consistent with a low-grade neuroendocrine/carcinoid tumor. Immunostaining for synaptophysin, chromogranin, CD56, and CAM5.2 were positive while staining for CK20 was negative. Given the absence of metastasis on radiographic and endoscopic evaluation, the patient was managed conservatively thereafter with observation. Despite having an indolent clinical course, resection is recommended for all rectal neuroendocrine tumors. Locoregional endoscopic resection versus radical resection can be used for adequate tissue removal depending on the characteristics of the tumor and the degree of invasion.