Current Landscape of Antibody-Drug Conjugate Development in Head and Neck Cancer.

Antibody-drug conjugates (ADCs) are fusions of therapeutic drugs and antibodies conjugated by a linker, designed to deliver a therapeutic payload to cells expressing the target antigen. By delivering the highly cytotoxic agent directly to cancer cells, ADCs are designed to enhance safety and broaden the therapeutic window. Recently, ADCs have demonstrated promising efficacy in various solid tumors and are rapidly expanding their indications. The prognosis of patients with advanced head and neck squamous cell carcinoma (HNSCC) remains poor, with no new therapeutics since the advent of anti-PD-1 antibodies in 2016, highlighting a critical need for innovative therapies. Recent preliminary results suggest that ADCs could be promising treatment options for HNSCC as they explore a variety of target antigens, payloads, and linkers. However, for successful adaptation of ADCs in the treatment of HNSCC, addressing key challenges such as payload toxicities, antigen heterogeneity, and adaptive resistance will be essential. Current research focused on new ADC structures, including multispecific antibodies and noncytotoxic payloads, and diverse combination approaches, show promise for future advancements.

Non-Centrosymmetric Single Crystalline Biomolecular Nano-Arrays for Responsive Electronics.

Herein, a novel strategy is reported for synthesizing libraries of single crystalline amino acid (AA) nanocrystals with control over size, anisotropy, and polymorphism by leveraging dip-pen nanolithography (DPN) and recrystallization via solvent vapor annealing. The crystals are prepared by first depositing nanoreactors consisting of a solvent with AAs, followed by water vapor-induced recrystallization. This leads to isotropic structures that are non-centrosymmetric with strong piezoelectric (g33 coefficients >1000 mVm N-1), ferroelectric, and non-linear optical properties. However, recrystallizing arrays of isotropic DL-alanine nanodot features with a binary solvent (water and ethanol) leads to arrays of 1D piezoelectric nanorods with their long axis coincident with the polar axis. Moreover, positioning nanoreactors containing AAs (the nanodot features) between micro electrodes leads to capillary formation, making the reactors anisotropic and facilitating piezoelectric nanorod formation between the electrodes. This offers a facile route to device fabrication. These as-fabricated devices respond to ultrasonic stimulation in the form of a piezoelectric response. The technique described herein is significant as it provides a rapid way of investigating non-centrosymmetric nanoscale biocrystals, potentially pivotal for fabricating a new class of stimuli-responsive devices such as sensors, energy harvesters, and stimulators.

Retrolabyrinthine Bone Thickness as a Radiologic Marker for the Hypoplastic Endotype in Menière Disease.

BACKGROUND AND PURPOSE: Menière disease (MD) manifests in 2 major endotypes: one with a hypoplastic, underdeveloped endolymphatic sac (MD-hp) and the other with a normally developed sac that degenerates over time (MD-dg). Determining the specific endotype in patients is important for predicting disease progression, tailoring patient counseling, and optimizing treatment strategies. Endotype diagnosis involves measuring an angular trajectory of the vestibular aqueduct (ATVA), with an ATVA ≥140° indicative of MD-hp and an ATVA ≤120° of MD-dg. However, assessing the ATVA can be challenging. This study aimed to explore the link between ATVA and the thickness of the retrolabyrinthine bone as an alternative diagnostic measure that could provide differentiation between MD endotypes using CT and MR imaging. MATERIALS AND METHODS: Retrospective review of CT temporal bone imaging from 32 adult patients with definite MD (60 ears) and 33 age-matched controls without MD or other inner ear symptoms (61 ears) was performed. The ATVA and retrolabyrinthine bone thickness were measured using uniform methodology on standardized axial CT images. Comparative analyses were performed to determine the correlation between ATVA and retrolabyrinthine bone thickness. Additionally, from a separate cohort of 11 patients (22 ears), CT and MR examinations of the temporal bone were retrospectively reviewed for retrolabyrinthine bone thickness measurements, to verify the correlation across the 2 modalities. RESULTS: The average retrolabyrinthine bone thickness was statistically significantly different between MD endotypes, being a mean of 0.8 (SD, 0.3) mm in patients with MD-hp (ATVA ≥140°) and 2.0 (SD, 0.9) mm in patients with MD-dg (ATVA ≤120°), with a consistent pattern of thin retrolabyrinthine bone in MD-hp and variable thickness in MD-dg. Receiver operating characteristic curve analysis within the MD cohort revealed that a retrolabyrinthine bone thickness ≥1.2 mm effectively rules out MD-hp. Excellent interrater reliability was noted for the retrolabyrinthine measurement, and there was near-perfect correlation between CT and MR measurements. CONCLUSIONS: Retrolabyrinthine bone thickness proved to be a useful and straightforward alternative marker for distinguishing MD endotypes, being particularly useful for excluding MD-hp. Including information on retrolabyrinthine bone thickness should be considered a routine part of reporting in the context of MD imaging.

Multisystem factors contributing to redundant intracranial vascular imaging in the ED.

PURPOSE: To evaluate the multisystem factors contributing to redundant neurovascular orders in the ED. METHODS: This was an IRB-approved, retrospective study, performed at a single institution examining a 5-year history of redundant CTA/MRA head and neck (HN) exams performed in the ED for patients with no documented clinical change in mental status/neurological exam necessitating additional imaging. Factors contributing to redundant ordering including provider experience, synchronous order placement, and radiologist recommendations were examined. Additionally, the impact of duplicative imaging in terms of medical cost and ED length of stay was evaluated. RESULTS: 250 patients met inclusion criteria with both CTA/MRA of the HN performed during a single ED encounter (total 500 exams). 190 (76%) redundant exams were not recommended by a radiologist and contributed to an added ED length of stay of 3.6 h on average. Provider experience was not a significant contributing factor. 60 (24%) of redundant exams were recommended by a radiologist and were most frequently CTAs needed to clarify an area of artifact/high-grade stenosis/occlusion on a primary MRA exam. CONCLUSION: Evaluation of contributing factors to redundant CTA/MRA HN exams ordering has highlighted multiple associated factors including provider experience, recommendations by radiologists for clarification of MRA findings, as well as systems processes related to synchronous CTA/MRA order placement.

Using Surface Composition and Energy to Control the Formation of Either Tetrahexahedral or Hexoctahedral High-Index Facet Nanostructures.

High-index facet nanoparticles with structurally complex shapes, such as tetrahexahedron (THH) and hexoctahedron (HOH), represent a class of materials that are important for catalysis, and the study of them provides a fundamental understanding of the relationship between surface structures and catalytic properties. However, the high surface energies render them thermodynamically unfavorable compared to low-index facets, thereby making their syntheses challenging. Herein, we report a method to control the shape of high-index facet Cu nanoparticles (either THH with {210} facets or HOH with {421} facets) by tuning the facet surface energy with trace amounts of Te atoms. Density functional theory (DFT) calculations reveal that the density of Te atoms on Cu nanoparticles can change the relative stability of the high-index facets associated with either the THH or HOH structures. By controlling the annealing conditions and the rate of Te dealloying from CuTe nanoparticles, the surface density of Te atoms can be deliberately adjusted, which can be used to force the formation of either THH (higher surface Te density) or HOH (lower surface Te density) nanoparticles.

Coronal Diffusion-Weighted Imaging Does Not Improve Detection of Posterior Fossa Infarcts Compared With Conventional Axial Diffusion-Weighted Imaging.

PURPOSE: Recent publications have suggested incorporating coronal diffusion-weighted imaging (DWI) sequences and axial DWI sequences to enhance the detection of posterior fossa infarcts (PFIs). This study evaluated the utility of coronal DWIs compared with axial DWIs for assessing PFIs in the emergency department (ED). METHODS: A retrospective, institutional review board-approved study was conducted at a level I stroke center, including 118 patients who presented to the ED between 2016 and 2023 with suspected PFI. Inclusion criteria involved patients who underwent emergent 1.5 T magnetic resonance imaging (MRI) and had axial and coronal DWI sequences. Two neuroradiologists independently evaluated the DWI sequences for PFI detection in 2 rounds, with a 4-week interval between rounds. The neuroradiologists assessed the quality of axial and coronal DWIs using a 5-point Likert scale. Descriptive statistics, interrater reliability, and marginal homogeneity tests were performed. RESULTS: Among the 118 MRI scans, 23 (19%) showed PFI on axial and coronal DWI sequences. All 23 cases were identified on axial DWI, whereas 8 cases of PFI (35%) were not detected on coronal DWI (P value = 0.013). No PFIs were observed on coronal DWI that was not identified on axial DWI. The quality scores for both raters were significantly higher for axial DWIs than coronal DWIs (P value <0.00001). CONCLUSION: Despite recent recommendations advocating for the inclusion of coronal DWI in PFI detection, this study's findings indicate no improvement in PFI detection or image quality using coronal DWI. Further research is necessary to validate these results and explore the potential benefits of incorporating coronal DWI in assessing posterior fossa strokes.

Spyglass: a framework for reproducible and shareable neuroscience research.

Scientific progress depends on reliable and reproducible results. Progress can also be accelerated when data are shared and re-analyzed to address new questions. Current approaches to storing and analyzing neural data typically involve bespoke formats and software that make replication, as well as the subsequent reuse of data, difficult if not impossible. To address these challenges, we created Spyglass, an open-source software framework that enables reproducible analyses and sharing of data and both intermediate and final results within and across labs. Spyglass uses the Neurodata Without Borders (NWB) standard and includes pipelines for several core analyses in neuroscience, including spectral filtering, spike sorting, pose tracking, and neural decoding. It can be easily extended to apply both existing and newly developed pipelines to datasets from multiple sources. We demonstrate these features in the context of a cross-laboratory replication by applying advanced state space decoding algorithms to publicly available data. New users can try out Spyglass on a Jupyter Hub hosted by HHMI and 2i2c: https://spyglass.hhmi.2i2c.cloud/.

Massilia litorea sp. nov., Marinobacter salinisoli sp. nov. and Rhodobacter xanthinilyticus sp. nov., isolated from coastal environments.

Three bacterial strains, namely LPB0304T, LPB0319T and LPB0142T, were isolated from coastal environments. The 16S rRNA gene sequences of the three isolates were found to show the highest sequence similarities to Massilia litorea (98.44 %), Marinobacter salinisoli (97.55 %) and Rhodobacter lacus (97.60 %), respectively. The low (<98.7 %) sequence similarities and tree topologies implied the novelty of the three isolates, representing novel genomic species of the genus Massilia, Marinobacter and Rhodobacter. Numerous biochemical and physiological features also supported the distinctiveness of the isolates from previously known species. Based on the phenotypic and phylogenetic data presented in this study, three novel species are suggested with the following names: Massilia litorea sp. nov. (LPB0304T=KACC 21523T=ATCC TSD-216T), Marinobacter salinisoli sp. nov. (LPB0319T=KACC 21522T=ATCC TSD-218T) and Rhodobacter xanthinilyticus sp. nov. (LPB0142T=KACC 18892T=JCM 31567T).

Universal primers for rift valley fever virus whole-genome sequencing.

Rift Valley fever (RVF) is a mosquito-borne zoonotic disease causing acute hemorrhagic fever. Accurate identification of mutations and phylogenetic characterization of RVF virus (RVFV) require whole-genome analysis. Universal primers to amplify the entire RVFV genome from clinical samples with low copy numbers are currently unavailable. Thus, we aimed to develop universal primers applicable for all known RVFV strains. Based on the genome sequences available from public databases, we designed eight pairs of universal PCR primers covering the entire RVFV genome. To evaluate primer universality, four RVFV strains (ZH548, Kenya 56 (IB8), BIME-01, and Lunyo), encompassing viral phylogenetic diversity, were chosen. The nucleic acids of the test strains were chemically synthesized or extracted via cell culture. These RNAs were evaluated using the PCR primers, resulting in successful amplification with expected sizes (0.8-1.7 kb). Sequencing confirmed that the products covered the entire genome of the RVFV strains tested. Primer specificity was confirmed via in silico comparison against all non-redundant nucleotide sequences using the BLASTn alignment tool in the NCBI database. To assess the clinical applicability of the primers, mock clinical specimens containing human and RVFV RNAs were prepared. The entire RVFV genome was successfully amplified and sequenced at a viral concentration of 108 copies/mL. Given the universality, specificity, and clinical applicability of the primers, we anticipate that the RVFV universal primer pairs and the developed method will aid in RVFV phylogenomics and mutation detection.

An efficient 3-approximation algorithm for the Steiner tree problem with the minimum number of Steiner points and bounded edge length.

We present improved algorithms for the Steiner tree problem with the minimum number of Steiner points and bounded edge length. Given n terminal points in a 2D Euclidean plane and an edge length bound, the problem asks to construct a spanning tree of n terminal points with minimal Steiner points such that every edge length of the spanning tree is within the given bound. This problem is known to be NP-hard and has practical applications such as relay node placements in wireless networks, wavelength-division multiplexing(WDM) optimal network design, and VLSI design. The best-known deterministic approximation algorithm has O(n3) running time with an approximation ratio of 3. This paper proposes an efficient approximation algorithm using the Voronoi diagram that guarantees an approximation ratio of 3 in O(n log n) time. We also present the first exact algorithm to find an optimal Steiner tree for given three terminal points in constant time. Using this exact algorithm, we improve the 3-approximation algorithm with better performance regarding the number of required Steiner points in O(n log n) time.

Bimolecularly passivated interface enables efficient and stable inverted perovskite solar cells.

Compared with the n-i-p structure, inverted (p-i-n) perovskite solar cells (PSCs) promise increased operating stability, but these photovoltaic cells often exhibit lower power conversion efficiencies (PCEs) because of nonradiative recombination losses, particularly at the perovskite/C60 interface. We passivated surface defects and enabled reflection of minority carriers from the interface into the bulk using two types of functional molecules. We used sulfur-modified methylthio molecules to passivate surface defects and suppress recombination through strong coordination and hydrogen bonding, along with diammonium molecules to repel minority carriers and reduce contact-induced interface recombination achieved through field-effect passivation. This approach led to a fivefold longer carrier lifetime and one-third the photoluminescence quantum yield loss and enabled a certified quasi-steady-state PCE of 25.1% for inverted PSCs with stable operation at 65°C for >2000 hours in ambient air. We also fabricated monolithic all-perovskite tandem solar cells with 28.1% PCE.

Clinical Effectiveness of Fluorescence Lymph Node Mapping Using ICG for Laparoscopic Right Hemicolectomy: A Prospective Case-Control Study.

BACKGROUND: The distinction between D3 lymph nodes and actual lymphatic pathways in primary tumors can be difficult during surgery, making it challenging to confirm the completeness of D3 lymph node dissection. Fluorescence lymph node mapping (FLNM) is a promising method for lymph node visualization. PURPOSE: This study aimed to assess whether FLNM enhances the effectiveness of D3 lymph node dissection in patients with right-sided colon cancer. METHODS: Endoscopic submucosal indocyanine green injection were performed on the distal margin of the colon cancer. In an FLNM group, the lymphatic drainage pathway and distribution of D3 lymph nodes were explored. Pathological evaluations were conducted for the fluorescent D3 and non-fluorescent D3 lymph nodes. RESULTS: The FLNM group showed a significantly higher number of harvested lymph nodes in the D3 area. In stage III patients, the proportion of D3 lymph node metastasis was significantly higher in the FLNM group. The harvested D3 lymph node count showed a proportional correlation with a metastatic lymph node count of up to 15. CONCLUSION: FLNM could be considered a promising new strategy to potentially increase harvested D3 lymph node counts in colon cancer surgery.

Spatial and temporal variations in trophic structure of fish assemblages in the Yellow Sea revealed by C and N stable isotopes.

In this study, we assessed spatial and temporal variations in the trophic structure of fish assemblages in the Yellow Sea during spring and summer 2022 and compared their isotopic niches between the Provisional Measure Zone (PMZ) and Korea's west areas (non-PMZ) within the Yellow Sea. Spatial and temporal differences in the diversity and dominant species of fish assemblages were found between the PMZ and non-PMZ areas between the seasons. The mean δ13C values of fish assemblages were relatively higher in the non-PMZ areas than in the PMZ areas. In contrast, no significant differences were found in the mean δ15N values between the areas. Generally, the isotopic niche indices were relatively narrow in the PMZ areas compared to those in the non-PMZ areas. Overall, these spatial differences between the PMZ and non-PMZ areas suggest different trophic diversity of fish assemblages, resulting from site-specific variations in environmental conditions and community composition.

The Development of a Permanent Implantable Spacer with the Function of Size Adjustability for Customized Treatment of Regurgitant Heart Valve Disease.

The Pivot Mandu is an innovative device featuring a leak-tight adjustable 3D balloon spacer, incorporating inner mesh support, an outer e-PTFE layer, and a compliant balloon in the middle layer with a specialized detachable system. To assess its feasibility, proof of concept was rigorously evaluated through bench testing and survival porcine animal experiments. The results demonstrated successful remote inflation of the balloon system, with the balloon spacer exhibiting sustained patent and functional integrity over an extended observation period of up to 6 months. A noteworthy feature of the newly designed 3D balloon spacer is its capability for easy size adjustment during procedures, enhancing its adaptability and practicality in clinical settings. This three-layered 3D balloon spacer, with its established long-term patency, exhibits highly encouraging outcomes that hold promise in overcoming the current limitations of spacer devices for heart valve diseases. Given the compelling results from preclinical investigations, the translation of the Pivot Mandu into human trials is strongly warranted.

Conversion of the bronchial tree into a conforming electrode to ablate the lung nodule in a porcine model.

BACKGROUND: Radiofrequency ablation (RFA) is one of the treatment options for lung nodules. However, the need for exact delivery of the rigid metal electrode into the center of the target mass often leads to complications or suboptimal results. To overcome these limitations, a concept of conforming electrodes using a flexible material has been tested in this study. METHODS: A bronchoscopy-guided RFA (CAROL) under a temperature-controlled mode was tested in in-vivo and ex-vivo porcine lungs. Gallium-based liquid metal was used for turning the bronchial tree into temporary RF electrodes. A customized bronchoscopy-guided balloon-tipped guiding catheter (CAROL catheter) was used to make the procedure feasible under fluoroscopy imaging guidance. The computer simulation was also performed to gain further insight into the ablation results. Safety was also assessed including the liquid metal remaining in the body. RESULTS: The bronchial electrode injected from the CAROL catheter was able to turn the target site bronchial air pipe into a temporally multi-tined RF electrode. The mean volume of Gallium for each effective CAROL was 0.46 ± 0.47 ml. The ablation results showed highly efficacious and consistent results, especially in the peripheral lung. Most bronchial electrodes were also retrieved by either bronchoscopic suction immediately after the procedure or by natural expectoration thereafter. The liquid metal used in these experiments did not have any significant safety issues. Computer simulation also supports these results. CONCLUSION: The CAROL ablation was very effective and safe in porcine lungs showing encouraging potential to overcome the conventional approaches.

Lung cancer can be treated by inserting a metal device into the lung via the throat and using this to send radio waves into the cancer. However, using a rigid metal device can cause damage to other areas of the lung and can only treat small cancers. Here, we describe an alternative method to treat lung cancers in which liquid metal is used to fill the spaces within the lung closest to the cancer. We demonstrate that this method can be used to treat cancer in a swine model of lung cancer. Given the positive results we obtained, we think this approach should be tested in a clinical trial in human patients with lung cancer, as it might improve cancer treatment.

Effect of Provider Type on Overutilization of CT Angiograms of the Head and Neck for Patients Presenting to the Emergency Department with Nonfocal Neurologic Symptoms.

PURPOSE: Overutilization of neuroimaging in the emergency department (ED), especially CT angiogram of the head and neck (CTAHN) examinations, contributes to rising health care expenditures, exposes patients to radiation, and may result in delays in care. We evaluated the rate of CTAHN overutilization for patients with nonfocal neurologic complaints in the ED and its potential association with patient clinical data, demographic data, and ED provider type. METHODS: This study was retrospective, was approved by an institutional review board, and was performed at a single institution, spanning a 6-year period. ED patients with nonfocal neurologic complaints who had a CTAHN examination with no history of trauma, recent surgery, or intracranial malignancy were included. Each CTAHN examination was categorized into one of four groups (0 = negative, 1 = chronic findings not related to presentation, 2 = nonacute and/or nonemergent findings or findings that may account for the presentation, and 3 = acute and/or emergent findings that may account for the presentation). Basic demographic data including patient age, patient sex, ordering ED provider type (attending, resident, nonphysician practitioner [(NPP]) were collected and analyzed using a multiple logistic regression analysis. RESULTS: A total of 960 CTAHN examinations were reviewed. The mean age of patients was 50 years (SD = 18 years), with 63% female patients and 37% male patients. Headache was the most frequent presentation (76%). A total of 75% of cases were negative, and 7% had chronic imaging findings not related to their ED presentation. A total of 12.5% of cases had nonacute and/or nonemergent findings possibly related to the presentation, and only 5.5% had acute and/or emergent findings related to ED presentation. A significantly greater proportion of CTAHN examinations ordered by NPPs, followed by the proportion ordered by ED residents, were negative or had no findings related to the patient presentation, and these patients were ultimately discharged to home. DISCUSSION: A total of 82% of ED CTAHN examinations performed for patients with nonfocal neurologic complaints had no actionable findings. These examinations are significantly more likely to be ordered by NPPs and ED residents.

Case report: Villaret's syndrome caused by middle ear adenocarcinoma in a cat.

A 7-year-old castrated male American Shorthair cat presented with left-side Horner's syndrome and voice change. The overall clinical presentation included dysphagia, intermittent coughing, unilateral miosis, and third eyelid protrusion of the left eye. A topical 1% phenylephrine was applied, and miosis and protrusion of the third eyelid disappeared within 20 min which suggested a post-ganglionic lesion. Laryngoscopy showed left-sided laryngeal paralysis. Computed tomography (CT) identified a mass lesion invading outside of the left tympanic bulla with osteolysis. Endoscopically assisted ventral bulla osteotomy was performed for tumor resection and definitive diagnosis. Middle ear adenocarcinoma was diagnosed based on histopathology. It appears that these neurological signs occurred due to adenocarcinoma in the tympanic bulla, penetrating the jugular foramen and the hypoglossal canal and damaging the cranial nerve IX (glossopharyngeal nerve), X (vagus nerve), XI (accessory nerve), and XII (hypoglossal nerve) and the sympathetic nerve. To the best of our knowledge, this is the first case report of Villaret's syndrome associated with middle ear adenocarcinoma affecting the nerves passing through the jugular foramen and hypoglossal canal in cats.

In Vitro Study of the Biological and Physical Properties of Dual-Cure Resin-Modified Calcium Silicate-Based Cement.

BACKGROUND: The aim of the present study was to compare the biological and mechanical properties of a novel dual-cure, resin-modified calcium silicate material, Theracal PT® (TP), with those of Theracal LC® (TL) and BiodentineTM (BD). METHODS: The cell counting kit-8 was used on human dental pulp cells to test cell the viability of the three materials. Antibacterial activity of TP, TL, and BD against Enterococcus faecalis was investigated under anaerobic conditions. The ability of the materials to support odontogenic differentiation was studied by examining the relative gene expression of osteocalcin (OCN), osteopontin (OPN), and Collagen I (ColI) using real-time polymerase chain reaction. For mechanical property tests, microhardness was evaluated using the Vickers microhardness (VHN) test, and the bond strength to the resin was evaluated using a shear bond test machine. RESULTS: There was no significant difference in cell viability between TL and TP after 48 h, and BD showed the highest cell viability, while TP showed the highest antibacterial effect. At the 12-h time point, there was no significant difference in ColI and OCN expression between BD and TP, but TP showed a higher expression of OPN than BD. However, at the 48-h time point, ColI and OCN showed higher levels of expression for BD than for TP and TL. At the same time point, only OPN had a higher diffusion for TP than for BD. TP demonstrated a VHN of approximately 30-35. This value was higher than that of TL and lower than that of BD. In contrast to VHN, the shear bond strength to resin was significantly higher for TL and TP than for BD. CONCLUSION: TP showed lower biocompatibility than BD but higher OPN expression and antibacterial effects than BD and TL. TP showed higher shear bond strength than BD and higher VHN than TL and BD at the 24-h time point.

Narrowband gamma oscillations propagate and synchronize throughout the mouse thalamocortical visual system.

Oscillations of neural activity permeate sensory systems. In the visual system, broadband gamma oscillations (30-80 Hz) are thought to act as a communication mechanism underlying perception. However, these oscillations show widely varying frequency and phase, providing constraints for coordinating spike timing across areas. Here, we examined Allen Brain Observatory data and performed causal experiments to show that narrowband gamma (NBG) oscillations (50-70 Hz) propagate and synchronize throughout the awake mouse visual system. Lateral geniculate nucleus (LGN) neurons fired precisely relative to NBG phase in primary visual cortex (V1) and multiple higher visual areas (HVAs). NBG neurons across areas showed a higher likelihood of functional connectivity and stronger visual responses; remarkably, NBG neurons in LGN, preferring bright (ON) versus dark (OFF), fired at distinct NBG phases aligned across the cortical hierarchy. NBG oscillations may thus serve to coordinate spike timing across brain areas and facilitate communication of distinct visual features during perception.

Clinicopathological and molecular genetic characteristics of primary gastric follicular lymphoma.

Primary gastric follicular lymphomas (FLs) have been rarely reported, and little is known about their characteristics. In the present study, we report 5 cases of primary gastric FL and describe their clinicopathological and molecular genetic features. A total of 7 samples from 5 patients were investigated for clinicopathological characteristics and somatic mutations by the targeted sequencing of 50 lymphoma-related genes. Two cases were identified as slightly elevated submucosal tumors and 3 cases as polypoid tumors. Histologically, all cases were low-grade FLs. The immunoprofile was CD20+/CD10+/BCL2+ in 4 cases and CD20+/CD10+/BCL2- in 1 case. The immunostaining pattern for CD21 was similar to that of classic FL. BCL2 rearrangement was not identified in fluorescence in situ hybridization studies in any of the 5 cases. Next-generation sequencing analysis showed mutations in genes involved in epigenetic modifications (KMT2D, ARID1A, EP300, and CREBBP), NK-kB pathway (CARD11), and JAK-STAT pathway as found in classic FL. All cases presented with clinical I without the involvement of regional or systemic lymph nodes. Four patients were well, whereas 1 patient who received endoscopic mucosal resection of tumor without additional chemotherapy or radiotherapy experienced 3 relapses. In conclusion, primary gastric FL is characterized by a low-grade neoplasm with infrequent BCL2 rearrangement. After resection of the lesion, additional treatment such as radiation therapy or chemotherapy is required as there is a possibility of recurrence.