Fluorine-18 FDG PET/CT and New NIMS Grading System for Chemotherapy Response in Breast Cancer.

Background: Positron emission tomography with computed tomography (PET-CT) using fluorine 18-fluorodeoxyglucose (F-18 FDG) is increasingly used to stage patients with locally advanced breast cancer and for assessing treatment response after neoadjuvant chemotherapy (NACT). Aims and Objectives: The aim of the study was to assess the correlation between PET-CT parameters and pathologic response of breast primary after NACT in breast cancer patients and to devise a grading system called NIMS grading system for response assessment using PET quantitative parameters. Materials and Methods: 55 patients who underwent F-18 FDG PET-CT before starting the therapy and again after completion of therapy were identified and included in the study. The clinical data and the histopathologic findings were recorded. All the patients received chemotherapy followed by surgery with axillary lymph node dissection. The PET-CT results were interpreted both qualitatively by visual analysis and quantitatively by estimating maximum Standardized uptake values(SUVmax) and other parameters - SUVmean, SUL, SUVBSA, Metabolic tumor volume (MTV) and Total lesion glycolysis (TLG). Results: The sensitivity and specificity of F-18 FDG PET-CT to detect the residual disease after neoadjuvant chemotherapy was 75.6% & 92.8% respectively. Differences between complete response and residual disease were significant for ΔSUVmax(p=0.005), ΔSUVmean(p=0.006), ΔSUL (0.005) and ΔSUVBSA(0.004), while ΔMTV and ΔTLG were not significantly different between the two groups. The new NIMS grading system included scoring of ΔSUVmax, ΔSUVBSA, ΔTLG and ΔMTV on scale of 1 to 4 and correlated well with PERCIST criteria. Conclusion: F-18 FDG PET-CT had a good accuracy in the detection of residual disease after completion of NACT. Pre chemotherapy PET-CT is not adequate to predict the response of primary tumour to chemotherapy. However, changes in the values of various PET-CT parameters are a sensitive tool to assess the response to chemotherapy. The new grading system is easy to use and showed good correlation to PERCIST.

Giant Genital Mass: Unveiling a Unique Case of Folliculocystic and Collagen Hamartoma.

Folliculocystic and collagen hamartoma (FCCH) is a rare entity, typically documented in males with tuberous sclerosis complex. Here, we report a unique case of FCCH in a 19-year-old female with an unusual presentation in the external genitalia. The patient presented with a progressively enlarging mass over three years, causing difficulties in walking and sitting. Examination revealed a 10 x 15 cm tender, lobulated, skin-colored tumor with comedo-like openings originating from the right labium majus, with satellite lesions on both labia majora. She had no other symptoms or history suggestive of tuberous sclerosis. Histopathological examination showed dilated hair follicles with keratin, perifollicular fibrosis, and thick dermal collagen bands extending into subcutaneous tissue, confirming FCCH. This case underscores the importance of considering FCCH in the differential diagnosis of genital masses, even without classical clinical associations. Our findings contribute to the limited literature on FCCH and highlight the need for further exploration and awareness within the medical community.

A Rare Hybrid Skin Cyst of the Scalp With Pilar and Apocrine Features.

Benign epithelial skin cysts containing multiple components of the folliculo-sebaceous apocrine unit are only rarely reported in the literature. Here, we describe a 12-year-old girl who presented with a cystic mass on the vertex of her scalp. Upon resection, it showed a hybrid benign skin cyst with interesting histological features of both pilar and apocrine differentiation. The clinicopathological and imaging findings of this unusual skin cyst, successfully managed by a plastic surgeon and neurosurgeon, are described. Pathologists and clinicians should be aware of this type of skin cyst rarely encountered in their clinical practice.

Right proximal tibia post-traumatic lipoma following a jogging fall.

This case report describes a 70-year-old woman who presented with a lump at the right knee. She had had a fall while jogging two years previously, followed by the development of a painless mass at the injury site. The mass had gradually increased in size over time. At presentation the physical examination revealed a soft, ill-defined mass, and magnetic resonance imaging confirmed a well-circumscribed subcutaneous soft tissue mass consistent with a lipoma. Given the asymptomatic nature and well-defined characteristics of the mass, the patient opted for conservative management with observation. This case highlights the importance of considering post-traumatic lipoma in the differential diagnosis of soft tissue masses, particularly in patients with a history of trauma. Such masses should be regularly monitored to allow timely intervention if indicated.

Effects of different post-harvest processing methods on changes in the active ingredients of licorice based on LC-MS and plant metabolomics.

INTRODUCTION: Licorice, the dried roots and rhizomes of the Glycyrrhiza uralensis Fisch., holds a prominent status in various formulations within the realm of Chinese medicinal practices. The traditional processing methods of licorice hinder quality assurance, thus prompting Chinese medicine researchers to focus on the fresh processing methods to enhancing processing efficiency and quality. OBJECTIVE: This study aimed to identify the differential compounds of licorice between traditional and fresh processing methods and provide a scientific basis for the fresh processing of licorice and for further research on the processing mechanism. METHODOLOGY: A methodology integrating ultra-performance liquid chromatography with quadrupole-time-of-flight tandem mass spectrometry combined with multivariate statistical analysis was employed to characterize the differential compounds present in licorice between traditional processing and fresh processing. RESULTS: The results derived from principal component analysis and heat map analyses underscored significant differences in the content of bioactive compounds between the two processing methods. By applying conditions of VIP > 1.5 and p < 0.05, a total of 38 differential compounds were identified through t tests, and the transformation mechanisms of select compounds were illustrated. CONCLUSION: The adoption of fresh processing techniques not only improved processing efficiency but also significantly enhanced the preservation of bioactive compounds within licorice. This research has established a rapid and efficient analytical method for the identification of differential compounds present in differently processed licorice products.

Differentiation of regioisomers of sulfobenzoic acid by traveling-wave ion mobility mass spectrometry.

An ion mobility mass spectrometry (IM-MS) investigation using a Synapt G2 mass spectrometer was conducted to separate anions generated from the three regioisomers of sulfobenzoic acid. The results revealed that the differences in arrival time distributions (ATDs) were inadequate to differentiate the isomers unambiguously. However, the ATD profiles of the product ions, generated by fragmenting the respective mass-selected m/z 201 precursor ions in the Trap region of the three-compartment traveling-wave ion guide of the Synapt G2 mass spectrometer, were distinctly different, enabling definitive differentiation of the isomers. An arrival-time peak for an ion of m/z 157 resulting from the loss of CO2 from the respective precursors was common to all three mobilograms. However, only the profile recorded from the para-isomer exhibited a unique arrival-time peak for an ion of m/z 137, originating from an SO2 loss. Such a peak corresponding to an SO2 loss was absent in the ATD profiles of the ortho- and meta-isomers. Additionally, the mobilogram of the meta-isomer displayed a unique peak at 3.42 ms. Based on its product ion spectrum, this peak was attributed to the bisulfite anion (m/z 81; HSO3-). Previously, this meta-isomer specific m/z 81 ion had been proposed to originate from a two-step process involving the intermediacy of an m/z 157 ion formed by CO2 loss. However, our detailed tandem mass spectrometric experiments suggest that the m/z 81 is not a secondary product but rather an ion that originated from a direct elimination of a benzyne derivative from the m/z 201 precursor ion.

Dependency of fentanyl analogue protomer ratios on solvent conditions as measured by ion mobility-mass spectrometry.

Recently, our group has shown that fentanyl and many of its analogues form prototropic isomers ("protomers") during electrospray ionization. These different protomers can be resolved using ion mobility spectrometry and annotated using mobility-aligned tandem mass spectrometry fragmentation. However, their formation and the extent to which experimental variables contribute to their relative ratio remain poorly understood. In the present study, we systematically investigated the effects of mixtures of common chromatographic solvents (water, methanol, and acetonitrile) and pH on the ratio of previously observed protomers for 23 fentanyl analogues. Interestingly, these ratios (N-piperidine protonation vs. secondary amine/O = protonation) decreased significantly for many analogues (e.g., despropionyl ortho-, meta-, and para-methyl fentanyl), increased significantly for others (e.g., cis-isofentanyl), and remained relatively constant for the others as solvent conditions changed from 100% organic solvent (methanol or acetonitrile) to 100% water. Interestingly, pH also had significant effects on this ratio, causing the change in ratio to switch in many cases. Lastly, increasing conditions to pH ≥ 4.0 also prompted the appearance of new mobility peaks for ortho- and para-methyl acetyl fentanyl, where all previous studies had only showed one single distribution. Because these ratios have promise to be used qualitatively for identification of these (and emerging) fentanyl analogues, understanding how various conditions (i.e., mobile phase selection and/or chromatographic gradient) affect their ratios is critically important to the development of advanced ion mobility and mass spectrometry methodologies to identify fentanyl analogues.

Distribution of active ingredients and quality control of Forsythia suspensa with AP-MALDI mass spectrometry imaging.

The fruits of Forsythia suspensa (F. suspensa) have been used as a traditional Chinese medicine for 2000 years. Currently, the quality control of F. suspensa strictly follows the instructions of Chinese Pharmacopeia, which mainly controls the content of forsythoside A, phillyrin, and volatile oil. In this study, air pressure MALDI mass spectrometry imaging (AP-MALDI MSI) was used to evaluate the quality of F. suspensa fruits and the distribution of dozens of active ingredients. The variation of active ingredients was measured for more than 30 batches of samples, regarding harvest time, cultivated environment, shelf-life, and habitat. Fifty-three active ingredients could be detected in F. suspensa fruits with AP-MALDI MSI. Seven active ingredients were upregulated, four ingredients downregulated, and 15 ingredients did not change in ripe fruits. A sharp variation of active ingredients in late September was observed for the Caochuan fruits harvested in 2019, which is closely related to the appearance of the ginger color of the pericarp under the microscope observation. The microscope observation is a reliable way to classify ripe and green fruits instead of outlook. Just considering forsythoside A and phillyrin, it is found that wild fruits are better than cultivated fruits, but cultivated fruits have high contents of other ingredients. The shelf-life of F. suspensa fruits is proposed to be 3 years, considering the 26 ingredients investigated. It was found that Luoning wild fruits are better than those from Caochuan with a new evaluation method. Mass spectrometry imaging is an easy, objective, and effective method to evaluate the quality of F. suspensa fruits.

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy decreases lean body mass and appendicular skeletal muscle mass index even until one year after the final treatment in patients with B-cell non-Hodgkin lymphoma.

Sarcopenia is an independent prognostic factor for several solid cancers, including B-cell non-Hodgkin lymphoma (B-NHL). However, previous reports have measured the parameters of loss of skeletal muscle as sarcopenia only once before chemotherapy and have predicted poor outcomes. In this study, changes in body composition were measured in patients who received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy for B-NHL using the InBody 720 analyzer throughout the therapy. Twenty-seven patients who achieved complete remission and survived for one year after the last cycle were included in the study. Body composition was evaluated immediately before initiation and fourth cycle, and one month and one year after the last cycle. Throughout the follow-up period, the lean body mass index (LBMI) and appendicular skeletal muscle mass index (ASMI) showed significant transient decreases even one year following the last cycle (p < 0.001, p = 0.002, respectively). Body fat index (BFI) and body fat percentage (BF%) decreased until one month after the last cycle; however, they reached levels higher than the baseline levels, +22.1% and +15.9%, respectively, at 1 year from the last cycle. The loss of skeletal muscle mass did not recover even one year after the last cycle. Interventions in nutritional management are needed to prevent sarcopenia in patients treated with R-CHOP therapy.

Evaluation of a mass trapping strategy to prevent mosquito nuisance in campsites of southern France.

Mosquito traps, historically used for surveillance and research, have gained prominence as a tool for mosquito control, amidst concern over the environmental impact and increased resistance to insecticide-based methods. In this study, we tested the effectiveness of a mass trapping barrier design with two types of traps, Mosquito Magnet (MM) traps and BG-Protector (BGP) traps. This experiment was conducted in three coastal camping areas in southern France between summer and autumn 2022, where the presence of floodwater mosquito species with anthropophilic preferences like Aedes caspius represents a year-long nuisance. MM traps were set around the campsite as a barrier to interfere with mosquitoes from entering the campsites, whereas BGP traps were set within the campsites, with the aim of diverting mosquitoes away from humans at peak activity hours. Over 210,000 mosquitoes of 11 species from 4 genera were collected by both trap types across treatment campsites, with no significant differences in mosquito community samplings between BGP and MM traps. Barrier traps effectively targeted Ae. caspius, reducing total mosquito abundance in two of the three study sites by 34% and 55%. This study provides valuable insights into the efficacy and feasibility of using mass trapping barriers as a complementary control strategy for mosquito species in wetlands.

Exploring Maillard reaction markers and melanoidins to investigate toxicological and antioxidant profiles of optimized expanded snacks from corn/common bean mixtures.

BACKGROUND: Extrusion cooking of cereal-legume flour mixture is an innovative strategy to introduce nutrient-enriched ready-to-eat snacks to the market. However, this thermal process triggers the formation of compounds that could impact safety aspects of these products. Maillard reaction markers and the end products known as melanoidins were evaluated to assess the toxicological and bioactive profiles of extruded snacks from corn-plus-common-bean-flour combinations. Different molecular weight fractions were isolated and purified to analyze their antioxidant activity and to investigate the role of melanoidins. RESULTS: The snack formulated with an 84:16 ratio of corn:common bean flours exhibited an enhanced toxicological profile. It displayed the lowest levels of acrylamide and furanic compounds, along with reduced blockage of lysine residues in the protein. Extrusion increased the antioxidant activity of uncooked flours (30 to 64%) and total phenolic compounds (26 to 50%), and decreased the available lysine (-72.7 to -79.5%). During the fractionation process, it was established that compounds within the range of 3-10 kDa made the greatest contribution to antioxidant activity. The fraction greater than 10 kDa, which included melanoidins, displayed 7 to 33% lower antioxidant activity. The purification of the fraction greater than 10 kDa revealed that pure melanoidins represented approximately one-third of the antioxidant activity in that fraction. Non-covalent adducts linked to the melanoidin core therefore had a relevant role in the antioxidant action of formulated snacks. CONCLUSION: This investigation illustrates the importance of considering both potential risks and associated benefits of compounds formed during the Maillard reaction while developing new extruded snacks. © 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

ADP-ribosylome analysis reveals homogeneous DNA-damage-induced serine ADP-ribosylation across wild-type and BRCA-mutant breast cancer cell lines.

ADP-ribosylation (ADPr) signaling plays a crucial role in DNA damage response. Inhibitors against the main enzyme catalyzing ADPr after DNA damage, poly(ADP-ribose) polymerase 1 (PARP1), are used to treat patients with breast cancer harboring BRCA1/2 mutations. However, resistance to PARP inhibitors (PARPi) is a major obstacle in treating patients. To understand the role of ADPr in PARPi sensitivity, we use liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze ADPr in six breast cancer cell lines exhibiting different PARPi sensitivities. We identify 1,632 sites on 777 proteins across all cell lines, primarily on serine residues, with site-specific overlap of targeted residues across DNA-damage-related proteins across all cell lines, demonstrating high conservation of serine ADPr-signaling networks upon DNA damage. Furthermore, we observe site-specific differences in ADPr intensities in PARPi-sensitive BRCA mutants and unique ADPr sites in PARPi-resistant BRCA-mutant HCC1937 cells, which have low poly(ADP-ribose) glycohydrolase (PARG) levels and longer ADPr chains on PARP1.

Assessment of the effect of 21-day head-down bed rest on the cardiovascular system by blood protein composition.

Head-down bed rest (HDBR) is one of the models of the physiological effects of weightlessness used, among other things, to assess the effect of hypokinesia on the physiological systems of the human body and, first of all, on the cardiovascular system. The aim of the work was to study the effect of 21 days of HDBR factors on the cardiovascular system based on blood proteomic profile data. It was revealed that HDBR conditions led to an increase in the levels of proteins of the complement and the coagulation cascade systems, platelet degranulation, fibrinolysis, acute phase proteins, post-translational modification of proteins, retinol-binding protein 4 (RBP4), apolipoprotein B, which are associated with cardiovascular diseases, and other proteins that affect the functions of endothelial cells. Blood levels of proteins involved in cytoskeletal remodelling, oxygen transport, heme catabolism, etc. have been shown to decrease during HDBR.

Left ventricular myxoma with carcinoid heart disease: A case report of a 14-year-old child from Jimma Medical Center of Ethiopia.

Understand the importance of considering alternative diagnosis in patients presenting with atypical features, specially when they are not responding to the standard treatment. Understand the importance of considering common presentations of rare cases. Underscoring the critical importance of timely recognition and appropriate management of potentially life-threatening conditions.

A combined association of obesity, alanine aminotransferase and creatinine with hyperuricemia in youth aged 13-20 years.

Background: Despite extensive research on hyperuricemia (HUA) in adults, there remains a dearth of studies examining this condition in youth. Consequently, our objective was to investigate the prevalence of HUA among youth in the United States, as well as identify the corresponding risk factors. Methods: This study employed a nationally representative subsample of 1,051 youth aged 13-20 from the US National Health and Nutrition Examination Survey (NHANES) conducted between January 2017 and March 2020. Univariate and multivariate techniques were utilized to examine the association between HUA and obesity, dietary nutrients, liver and kidney function, glucose and lipid metabolism, inflammation, and other indicators in the adolescent population. Results: The study encompassed a cohort of 1,051 youth aged 13-20 years, comprising 538 boys and 513 girls. The overall prevalence of HUA was found to be 7% (74 out of 1,051). Univariate analysis revealed that the HUA group exhibited greater age, body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR). Additionally, the prevalence of obesity was significantly higher in the HUA group compared to the non- HUA group (all p < 0.05). Regarding biochemical indicators, the levels of urea nitrogen, creatinine (Cr), alanine aminotransferase (ALT), glutamic oxalic aminotransferase (AST), gamma-glutamyl transferase (GGT), total cholesterol (TC), triglyceride (TG), and HS C reactive protein (Hs CRP) were found to be significantly higher in the HUA group compared to the non-HUA group (all p < 0.05). Further analysis using binary logistics regression showed that BMI (p = 0.024, OR1.158, 95%CI1.019-1.316), ALT (p = 0.020, OR1.032, 95%CI1.005-1.059), and Cr (p = 0.016, OR1.028, 95%CI1.005-1.051) were identified as risk factors for HUA, after controlling for age, gender, BMI, WC, HC, WHR, ALT, AST, GGT, TG, TC, Cr, Hs CRP, and other indicators. Interestingly, neither univariate nor multivariate analysis found any association between dietary nutrients and the risk of HUA (all p > 0.05). Conclusion: High BMI remains a major risk factor for HUA in US youth aged 13-20 years, and ALT and Cr levels should be closely monitored along with serum uric acid.

IgG4-related disease with nasopharyngeal malignancy-like manifestations.

Background: IgG4-related disease (IgG4-RD) was characterized by single or multiple masses in organs, which may mimic various inflammatory and malignant diseases. Here, we summarize 4 patients with aggressive manifestations of IgG4-RD that mimic nasopharynx cancer to provide some new sights for the diagnosis of IgG4-RD. Case summary: Four patients were included in our series. The age ranged from 53 to 64 years old, and the duration of the disease ranged from 4 to 6 months. The chief complaints included headache, rhinorrhea, or diplopia. All patients had more than 10 IgG4+ plasma cells/HPF in immunohistochemistry with plasma lgG4 levels ranging from 218 mg/dL to 765 mg/dL. All of them met the diagnostic criteria of lgG4-RD. Conclusion: The described case is highly similar to the clinical manifestations of nasopharyngeal carcinoma. Although pathology is the gold standard, there are still limitations. Serological IgG4 can help confirm the diagnosis. Timely diagnosis of IgG4-RD is of great significance in preventing secondary organ damage in patients with active diseases.

Changes in protein fluxes and gene expression in non-injured muscle tissue distant from an acute myotoxic injury in male mice.

The response to acute myotoxic injury requires stimulation of local repair mechanisms in the damaged tissue. However, satellite cells in muscle distant from acute injury have been reported to enter a functional state between quiescence and active proliferation. Here, we asked whether protein flux rates are altered in muscle distant from acute local myotoxic injury and how they compare to changes in gene expression from the same tissue. Broad and significant alterations in protein turnover were observed across the proteome in the limb contralateral to injury during the first 10 days after. Interestingly, mRNA changes had almost no correlation with directly measured protein turnover rates. In summary, we show consistent and striking changes in protein flux rates in muscle tissue contralateral to myotoxic injury, with no correlation between changes in mRNA levels and protein synthesis rates. This work motivates further investigation of the mechanisms, including potential neurological factors, responsible for this distant effect. KEY POINTS: Previous literature demonstrates that stem cells of uninjured muscle respond to local necrotic muscle tissue damage and regeneration. We show that muscle tissue that was distant from a model of local necrotic damage had functional changes at both the gene expression and the protein turnover level. However, these changes in distant tissue were more pronounced during the earlier stages of tissue regeneration and did not correlate well with each other. The results suggest communication between directly injured tissue and non-affected tissues that are distant from injury, which warrants further investigation into the potential of this mechanism as a proactive measure for tissue regeneration from damage.

Investigating local trawl fishing as a source of plastic beach litter.

This paper uses a particle tracking model to simulate the distribution of fishing-related marine-sourced plastic litter from demersal trawling activities along the Atlantic coast of Scotland. The modelled fishing litter dispersed widely across the region, with ∼50% of the particles beaching along the northwestern Scottish coast after a year-long simulation. The model was tuned using observations of beached litter loadings along the same coastline to estimate the annual input, by mass, of small (<1 kg) plastic litter. Model results suggest that between 107 g and 280 g of small fishing-related litter enters the ocean per hour of fishing, resulting in an estimated 234 t to 614 t of small fishing-related litter entering the ocean annually on the Scottish west coast. These results suggest that fishing on the Atlantic coast of Scotland may be a significant source of marine plastic. However, more modelled and observational data are required to reduce uncertainty.

A combination of multiple LC-MS approaches for the comprehensive characterization of cysteine-linked ADCs.

Antibody-drug conjugates (ADCs) represent the forefront of the next generation of biopharmaceuticals. An ADC typically comprises an antibody covalently linked to a cytotoxic drug via a linker, resulting in a highly heterogeneous product. This study focuses on the analysis of a custom-made cysteine-linked ADC. Initially, we developed a LC-MS-based characterization workflow using brentuximab vedotin (Adcetris®), encompassing native intact MS, analysis of reduced chains and subunits under denaturing condition, peptide mapping and online strong cation exchange chromatography coupled with UV and mass spectrometry detection (SCX-UV-MS) applied for brentuximab vedotin first time reported. Subsequently, we applied this in-depth characterization workflow to a custom-made cysteine-linked ADC. The measured drug-to-antibody ratio(DAR) of this ADC is 6.9, further analysis shown that there is a small amount of unexpected over-conjugation. Over-conjugation sites were successfully identified using multiple UHPLC-MS based characterization techniques. Also, one competitively cysteine-conjugated impurity was observed in native intact MS results, by combing native intact MS, reduced chains, subunit analysis and peptide mapping results, the impurity conjugation sites were also identified. Since this molecule is at early development stage, this provides important information for conjugation process improvement and link-drug material purification. SCX-UV-MS approach can separate the custom-made cysteine-linked ADC carrying different payloads and reduce the complexity of the spectra. The integrated approach underscores the significance of combining the SCX-UV-MS online coupling technique with other characterization methods to elucidate the heterogeneity of cysteine-linked ADCs.

Molecular mechanism of contactin 2 homophilic interaction.

Contactin 2 (CNTN2) is a cell adhesion molecule involved in axon guidance, neuronal migration, and fasciculation. The ectodomains of CNTN1-CNTN6 are composed of six Ig domains (Ig1-Ig6) and four FN domains. Here, we show that CNTN2 forms transient homophilic interactions (KD ∼200 nM). Cryo-EM structures of full-length CNTN2 and CNTN2_Ig1-Ig6 reveal a T-shaped homodimer formed by intertwined, parallel monomers. Unexpectedly, the horseshoe-shaped Ig1-Ig4 headpieces extend their Ig2-Ig3 tips outwards on either side of the homodimer, while Ig4, Ig5, Ig6, and the FN domains form a central stalk. Cross-linking mass spectrometry and cell-based binding assays confirm the 3D assembly of the CNTN2 homodimer. The interface mediating homodimer formation differs between CNTNs, as do the homophilic versus heterophilic interaction mechanisms. The CNTN family thus encodes a versatile molecular platform that supports a very diverse portfolio of protein interactions and that can be leveraged to strategically guide neural circuit development.