Development and Validation of a Machine Learning-based, Point-of-Care Risk Calculator for Post-ERCP Pancreatitis and Prophylaxis Selection.

BACKGROUND AND AIMS: A robust model of post-ERCP pancreatitis (PEP) risk is not currently available. We aimed to develop a machine learning-based tool for PEP risk prediction to aid in clinical decision-making related to periprocedural prophylaxis selection and post-procedural monitoring. METHODS: Feature selection, model training, and validation were performed using patient-level data from 12 randomized controlled trials. A gradient-boosted machine (GBM) model was trained to estimate PEP risk and the performance of the resulting model was evaluated using the area under the receiver operating curve (AUC) with 5-fold cross-validation. A web-based clinical decision-making tool was created, and a prospective pilot study was performed using data from ERCPs performed at the Johns Hopkins Hospital over a one-month period. RESULTS: A total of 7389 patients were included in the GBM with an 8.6% rate of PEP. The model was trained on twenty PEP risk factors and 5 prophylactic interventions (rectal non-steroidal anti-inflammatory drugs [NSAID], aggressive hydration, combined rectal NSAID and aggressive hydration, pancreatic duct [PD] stenting, and combined rectal NSAID and PD stenting). The resulting GBM model had an AUC of 0.70 (65% specificity, 65% sensitivity, 95% negative predictive value, 15% positive predictive value). A total of 135 patients were included in the prospective pilot study, resulting in an AUC of 0.74. CONCLUSIONS: This study demonstrates the feasibility and utility of a novel machine learning-based PEP risk estimation tool with high negative predictive value to aid in prophylaxis selection and identify patients at low risk who may not require extended post-procedure monitoring.

Study on Pyridine-Boryl Radical-Promoted, Ketyl Radical-Mediated Carbon-Carbon Bond-Forming Reactions.

Ketyl radicals are synthetically versatile reactive species, but their applications have been hampered by harsh generation conditions employing highly reducing metals. Recently, the pyridine-boryl radical received wide attention as a promising organic reductant because of its mildness as well as convenience in handling. While probing the utility of the pyridine-boryl radical, our group observed facile pinacol coupling reactivity that had not been known at that time. This serendipitous finding was successfully rendered into a practical synthesis of tetraaryl-1,2-diols in up to 99% yield within 1 h. Subsequently, upon examinations of various reaction manifolds, a diastereoselective ketyl-olefin cyclization was accomplished to produce cycloalkanols such as trans-2-alkyl-1-indanols. Compared to the previous methods, the stereocontrolling ability was considerably enhanced by taking advantage of the structurally modifiable boryl group that would be present near the bond-forming site. In this full account, our synthetic efforts with the O-boryl ketyl radicals are disclosed in detail, covering the discovery, optimization, scope expansion, and mechanistic analysis, including density functional theory (DFT) calculations.

Molecular Aggregation Behavior and Microscopic Heterogeneity in Binary Osmolyte-Water Solutions.

Osmolytes, small organic compounds, play a key role in modulating the protein stability in aqueous solutions, but the operating mechanism of the osmolyte remains inconclusive. Here, we attempt to clarify the mode of osmolyte action by quantitatively estimating the microheterogeneity of osmolyte-water mixtures with the aid of molecular dynamics simulation, graph theoretical analysis, and spatial distribution measurement in the four osmolyte solutions of trimethylamine-N-oxide (TMAO), tetramethylurea (TMU), dimethyl sulfoxide, and urea. TMAO, acting as a protecting osmolyte, tends to remain isolated with no formation of osmolyte aggregates while preferentially interacting with water, but there is a strong aggregation propensity in the denaturant TMU solution, characterized by favored hydrophobic interactions between TMU molecules. Taken together, the mechanism of osmolyte action on protein stability is proposed as a comprehensive one that encompasses the direct interactions between osmolytes and proteins and indirect interactions through the regulation of water properties in the osmolyte-water mixtures.

Unraveling the interplay of temperature with molecular aggregation and miscibility in TEA-water mixtures.

In the phase diagram of binary liquid mixtures, a miscibility gap is found with the concomitant liquid-liquid phase separation, wherein temperature is a key parameter in modulating the phase behavior. This includes critical temperatures such as the lower critical solution temperature (LCST) and upper critical solution temperature (UCST). Using a comprehensive approach including molecular dynamics (MD) simulation, graph theoretical analysis and spatial inhomogeneity measurement in an LCST-type mixture, we attempt to establish the relationship between the molecular aggregation pattern and phase behavior in TEA-water mixtures. At lower temperatures of binary liquid mixtures, TEA molecules tend to aggregate while simultaneously interacting with water forming a homogeneous solution. As the temperature increases, these TEA aggregates tend to self-associate by minimizing the interaction with water, which facilitates formation of two distinct liquid phases in the binary liquid. The spatial distribution analysis also reveals that the TEA aggregates compatible with water promote uniform distribution of water molecules, maintaining a homogeneous solution, while the water-incompatible ones generate isolation of water H-bond aggregates, leading to liquid-liquid phase separation in the binary system. This current study on temperature-induced molecular aggregation behavior is anticipated to contribute to a critical understanding of the phase behavior in binary liquid mixtures, including UCST, LCST, and reentrant phase behavior.

Fluorine-Assisted Rearrangement of Geminal Azidofluorides to Imidoyl Fluorides.

Organoazide rearrangement constitutes versatile synthetic strategies but typically requires an extremely strong acid and/or a high reaction temperature. Our group recently discovered the remarkable accelerating effect of the geminal fluorine substituent that enables the facile rearrangement of azides into imidoyl fluorides without the aid of acid under much milder reaction conditions. The role of geminal fluorine was elucidated by both experimental and computational investigations. This new reactivity led to the development of a practical one-step tandem preparative method for potentially useful and bench-stable imidoyl fluorides from a wide range of structurally diverse geminal chlorofluorides. Our additional efforts to expand the reaction scope regarding the migrating group, halogen, and carbonyl function are described, and the synthetic utility of the imidoyl fluoride products was demonstrated in hopes of promoting the use of this under-appreciated functional group in the synthetic organic community.

Gut microbiota differences induced by Toxoplasma gondii seropositivity in stray cats in South Korea.

T. gondii is a highly prevalent parasite worldwide, with cats serving as its final host. However, few studies have investigated the impact of T. gondii infection on cat gut microbiota. Therefore, this study examined the influence of T. gondii infection on the gut microbiota of stray cats and identified potential pathogens in their feces. This study examined T. gondii infection through blood of stray cats and the influence of microbiota in their feces using 16S rRNA gene amplicon sequencing. The results revealed significant differences in gut microbiota composition and diversity between the T. gondii seropositive and seronegative groups. Seropositive samples displayed a lower number of operational taxonomic units and reduced Shannon index than the seronegative samples. The seropositive and seronegative groups exhibited enrichment of taxa, including Escherichia and Enterobacteriaceae and Collinsella, Bifidobacterium, and Roseburia, respectively. Furthermore, potential pathogen species, including Campylobacter, Escherichia, and Streptococcus, were identified in the fecal samples. These findings suggest that T. gondii infection significantly impacts gut microbiota composition and diversity in stray cats. Additionally, an increased potential pathogen load, represented by Escherichia spp., was observed. These results underscore the importance of monitoring the prevalence of zoonotic pathogens in stray cats, as they can serve as reservoirs for zoonotic diseases.

The Effect of Epiphysiodesis on the Longitudinal Bone Growth of Hands or Feet in Children With Macrodactyly Based on Long-term Quantitative Analysis.

BACKGROUND: Treatment protocols for macrodactyly have not been elucidated due to its rarity and variety of clinical manifestations. This study aims to share our long-term clinical results of epiphysiodesis in children with macrodactyly. METHODS: A retrospective chart review was performed for 17 patients with isolated macrodactyly treated with epiphysiodesis over 20 years. Length and width of each phalanx in both the affected finger and the corresponding unaffected finger in the contralateral hand were measured. Results were presented in ratios of the affected to unaffected side for each phalanx. Measuring of length and width of phalanx was performed preoperatively and postoperatively at 6, 12, and 24 months, and the last follow-up session. Postoperative satisfaction scoring was done with visual analogue scale. RESULTS: The mean follow-up period was 7 years and 2 months. In the proximal phalanx, length ratio significantly decreased compared with preoperative state at after more than 24 months, in the middle phalanx after 6 months, in the distal phalanx after 12 months. When classified by the growth patterns, the progressive type showed significant decrease in length ratio at after 6 months, and the static type after 12 months. Patients were overall satisfied with the results. CONCLUSION: Epiphysiodesis effectively regulated longitudinal growth with different degree of control for different phalanges in the long-term follow-up.

Giant Pilomatricoma Mistaken for a Malignant Tumor.

Pilomatricomas are tumors originating from the matrices of hair follicles. Giant pilomatricomas, defined as pilomatricomas that are 5 cm or larger, are benign but may appear malignant clinically. We present the case of a 69-year-old man with a rapidly growing mass on his scalp. When he visited our department, the tumor measured 10.0×6.0×4.0 cm and showed inflammation and ulceration. Magnetic resonance imaging and 18 F-fluorodeoxyglucose positron emission tomography-computed tomography showed findings resembling lymph node metastasis from a malignant tumor. However, upon an incisional biopsy, the tumor was diagnosed as a pilomatricoma. Therefore, we performed an excisional biopsy instead of radical surgery and lymph node dissection. The tumor was ultimately diagnosed as a giant pilomatricoma based on the excisional biopsy, and the patient received reconstruction only at the site of the defect. A giant pilomatricoma can be mistaken for a malignant tumor due to its characteristics. In such uncertain cases, it can be helpful to first perform an excisional biopsy.

Engineering pupil function for optical adversarial attacks.

Adversarial attacks inject imperceptible noise to images to deteriorate the performance of deep image classification models. However, most of the existing studies consider attacks in the digital (pixel) domain where an image acquired by an image sensor with sampling and quantization is recorded. This paper, for the first time, introduces a scheme for optical adversarial attack, which physically alters the light field information arriving at the image sensor so that the classification model yields misclassification. We modulate the phase of the light in the Fourier domain using a spatial light modulator placed in the photographic system. The operative parameters of the modulator for adversarial attack are obtained by gradient-based optimization to maximize cross-entropy and minimize distortion. Experiments based on both simulation and a real optical system demonstrate the feasibility of the proposed optical attack. We show that our attack can conceal perturbations in the image more effectively than the existing pixel-domain attack. It is also verified that the proposed attack is completely different from common optical aberrations such as spherical aberration, defocus, and astigmatism in terms of both perturbation patterns and classification results.

α-Fluoroamine synthesis via P(III)-mediated deoxygenative geminal fluorosulfonimidation of 1,2-diketones.

A deoxygenative geminal fluorosulfonimidation of 1,2-diketones was achieved for the synthesis of tetrasubstituted α-fluoroamines under mild conditions. In this study, a transition metal-free formal N-F insertion of N-fluorobenzenesulfonimide was enabled via the Kukhtin-Ramirez reaction employing a dealkylation-resistant P(III) reagent developed in our laboratory. Computational analysis was also performed to obtain a general mechanistic picture, which explained the reactivity and selectivity for this type of reaction.

Vibrational Spectroscopic Map, Vibrational Spectroscopy, and Intermolecular Interaction.

Vibrational spectroscopy is an essential tool in chemical analyses, biological assays, and studies of functional materials. Over the past decade, various coherent nonlinear vibrational spectroscopic techniques have been developed and enabled researchers to study time-correlations of the fluctuating frequencies that are directly related to solute-solvent dynamics, dynamical changes in molecular conformations and local electrostatic environments, chemical and biochemical reactions, protein structural dynamics and functions, characteristic processes of functional materials, and so on. In order to gain incisive and quantitative information on the local electrostatic environment, molecular conformation, protein structure and interprotein contacts, ligand binding kinetics, and electric and optical properties of functional materials, a variety of vibrational probes have been developed and site-specifically incorporated into molecular, biological, and material systems for time-resolved vibrational spectroscopic investigation. However, still, an all-encompassing theory that describes the vibrational solvatochromism, electrochromism, and dynamic fluctuation of vibrational frequencies has not been completely established mainly due to the intrinsic complexity of intermolecular interactions in condensed phases. In particular, the amount of data obtained from the linear and nonlinear vibrational spectroscopic experiments has been rapidly increasing, but the lack of a quantitative method to interpret these measurements has been one major obstacle in broadening the applications of these methods. Among various theoretical models, one of the most successful approaches is a semiempirical model generally referred to as the vibrational spectroscopic map that is based on a rigorous theory of intermolecular interactions. Recently, genetic algorithm, neural network, and machine learning approaches have been applied to the development of vibrational solvatochromism theory. In this review, we provide comprehensive descriptions of the theoretical foundation and various examples showing its extraordinary successes in the interpretations of experimental observations. In addition, a brief introduction to a newly created repository Web site (http://frequencymap.org) for vibrational spectroscopic maps is presented. We anticipate that a combination of the vibrational frequency map approach and state-of-the-art multidimensional vibrational spectroscopy will be one of the most fruitful ways to study the structure and dynamics of chemical, biological, and functional molecular systems in the future.

Effectiveness and Safety of Lumen-Apposing Metal Stents in Endoscopic Interventions for Off-Label Indications.

BACKGROUND: Although released only for drainage of pseudocyst and walled-off necrosis (WON) with ≤ 30% solid debris, the utilization of lumen-apposing metal stent (LAMS) in "real-world" practice has deviated from approved indications. We evaluated the contemporary use of LAMS and associated clinical, procedural outcomes in the setting of a tertiary referral center in the USA. METHODS: Data from 303 consecutive patients who underwent LAMS placement were analyzed. Outcomes included technical and clinical success rates and adverse events. RESULTS: Of 303 patients, 190 (62.7%) received LAMS for off-label indications. The latter included gallbladder drainage (n = 56, 18.5%), gastroenterostomy (n = 52, 17.2%), treatment of gastrointestinal strictures (n = 37, 12.2%), biliary drainage (n = 20, 6.6%), temporary gastric access for endoscopy (n = 13, 4.3%), symptomatic WON with > 30% solid debris (n = 8, 2.6%), and miscellaneous (n = 4, 1.3%). Technical success rates in the on- and off-label arm were 98.2% and 95.8%, respectively (P = .331; 95% CI 0.08 to 1.96). Clinical success rates in the on- and off-label arm were 89.4% and 83.2%, respectively (P = .137; 95% CI 0.28 to 1.19). The rate of adverse events was 20.5% (n = 39) in the off-label arm and 16.8% (n = 19) in the on-label arm (P = .242; 95% CI 0.69 to 2.34). CONCLUSION: Off-label use of LAMS out-numbered on-label use in our practice. The safety profile between the groups was similar and with the exception of refractory stricture treatment, efficacy was comparable.

Electric Scooter-Related Trauma in Korea.

BACKGROUND: The number of users of electric scooters, which provide swift and convenient mobility options, has increased sharply over recent years as their distribution as a shared service has expanded. Although the number of accidents and related damage has increased accordingly, limited research has analyzed data on the new types of accidents arising from electric scooters. This study aimed to analyze data on trauma characteristics due to accidents that occurred during electric scooter use. METHODS: A retrospective chart review was conducted for patients who visited the regional trauma center of our institute due to electric scooter accidents from April 2018 to October 2021. Information was extracted on helmet-wearing status, sex, age, drinking status, accident timeframe, accident mechanism, electric scooter proficiency (period of use), injury severity, severe trauma, lethality, admission to the intensive care unit, surgery under general anesthesia, and the trauma region. RESULTS: Among the 108 patients involved in electric scooter accidents, 92 patients were not wearing a helmet. Eighty-nine patients (85.2%) were male. The average age of the patients without a helmet was 31.3 years, while that of patients with a helmet was 34.1 years. The most frequent causes of accidents were lack of electric scooter operation experience and falling off the scooter due to obstacles (90 cases). Whether surgery was performed under general anesthesia was not associated with helmet use or non-use, although all patients who underwent facial fracture surgery were not wearing a helmet. CONCLUSION: The craniofacial region was most frequently affected in electric scooter accidents and wearing a helmet was the best way to prevent craniofacial trauma. Although helmet-wearing is mandatory, the majority of treated patients were not wearing a helmet at the time of injury. Thus, there is an urgent need to introduce a helmet rental system, as well as strict legal requirements, to improve this situation.

Face Autotransplantation After an Accident.

ABSTRACT: Microsurgical replantation is considered the best method to treat avulsion or amputation injuries of unique head parts, including the scalp, eyelid, nose, ear, lip, and tongue. However, there is currently no report on microsurgical replantation of substi-tutable facial tissues in the literature. This report presents a patient with avulsed facial composite tissue composed of the skin and subcutaneous layers treated by microsurgical replantation. The present case shows that microsurgical replantation of small facial composite tissues is feasible. The authors suggest that the indication spectrum for microsurgical replantation should be expanded beyond current clinical practice.

Identification of New Non-BBB Permeable Tryptophan Hydroxylase Inhibitors for Treating Obesity and Fatty Liver Disease.

Serotonin (5-hydroxytryptophan) is a hormone that regulates emotions in the central nervous system. However, serotonin in the peripheral system is associated with obesity and fatty liver disease. Because serotonin cannot cross the blood-brain barrier (BBB), we focused on identifying new tryptophan hydroxylase type I (TPH1) inhibitors that act only in peripheral tissues for treating obesity and fatty liver disease without affecting the central nervous system. Structural optimization inspired by para-chlorophenylalanine (pCPA) resulted in the identification of a series of oxyphenylalanine and heterocyclic phenylalanine derivatives as TPH1 inhibitors. Among these compounds, compound 18i with an IC50 value of 37 nM was the most active in vitro. Additionally, compound 18i showed good liver microsomal stability and did not significantly inhibit CYP and Herg. Furthermore, this TPH1 inhibitor was able to actively interact with the peripheral system without penetrating the BBB. Compound 18i and its prodrug reduced body weight gain in mammals and decreased in vivo fat accumulation.

Ultrasonographic anatomy of posterior antebrachial cutaneous nerve in healthy subjects.

INTRODUCTION/AIMS: The posterior antebrachial cutaneous nerve (PACN) is one of the cutaneous branches of the radial nerve, and receives sensory input from the posterior arm and forearm. The aim of this study is to describe the ultrasonographic anatomy of the PACN. METHODS: PACN and its branches were scanned using ultrasonography in 30 healthy volunteers. The distances between the epicondylar line and the bifurcation site of each branch of PACN (A) point of separation of the radial nerve and the PACN, (B) point of separation of the anterior and posterior divisions, (C) point of bifurcation of the posterior division into the epicondylar and anconeus branches), cross-sectional areas and depths from the skin surface to each nerve at positions A, B, and C were measured. RESULTS: The mean distance from the epicondylar line to A, B, and C was 10.01 ± 0.82 cm, 7.46 ± 0.98 cm, and 4.02 ± 1.16 cm, respectively. The mean depth from the skin surface at A, B, and C was 1.00 ± 0.19 cm, 0.72 ± 0.19 cm, and 0.51 ± 0.12 cm, respectively. DISCUSSION: Ultrasonographic visualization of the PACN and its major branches was feasible. The reference values in this study may be helpful for more accurate sonographic assessment and electrophysiologic study, and contribute to safer interventions around the elbow region.

Extracellular vesicles of Echinococcus granulosus have therapeutic effects in allergic airway inflammation.

BACKGROUND: Previous studies have shown that Echinococcus granulosus cystic fluid can alleviate Th2 allergic airway inflammatory responses by increasing the number of CD4+ CD25+ Foxp3+ T (regulatory T; Treg) cells. Parasite-derived extracellular vesicles (EV) are known to not only promote parasite infection by communicating between parasites but also regulate the inflammatory response by acting as an immunomodulatory agent in the host. METHODS: To evaluate the effect of EV extracted from the cystic fluid of E. granulosus on allergic airway inflammation, gene expression was investigated after administering EV to mouse lung epithelial cells (MLE-12) following 2 h of pretreatment with Aspergillus proteins. An allergic airway inflammation animal model was used to investigate the regulation of the inflammatory response by EV and induced with ovalbumin. RESULTS: EV treatment significantly reduced airway resistance and the number of eosinophils and other immune cells in the bronchoalveolar lavage fluid and Th2- and Th17-related cytokine levels. EV pretreatment decreased the number of IL-4+ CD4+ T cells and increased the number of Treg cells in the lung-draining lymph nodes and spleen. CONCLUSIONS: Echinococcus granulosus cystic fluid derived EV ameliorated Th2 allergic airway inflammatory through Treg cells, similar to whole cystic fluid treatment. Thus, EV may be important immunomodulatory molecules in cystic fluid.

Can prophylactic argon plasma coagulation reduce delayed post-papillectomy bleeding? A prospective multicenter trial.

BACKGROUND AND AIM: Endoscopic post-papillectomy bleeding occurs in 3% to 20% of the cases, and delayed bleeding is also problematic. However, there is no consensus on how to reduce delayed post-papillectomy bleeding. The aim of this study was to evaluate the efficacy of prophylactic argon plasma coagulation (APC) to minimize delayed bleeding and reduce the persistence of residual tumors after endoscopic papillectomy. METHODS: In a prospective pilot study of patients with benign ampullary tumors, the prophylactic APC group underwent APC at the resection margin following a conventional snaring papillectomy. Then, 24 h later after the papillectomy, all patients underwent a follow-up duodenoscopy to identify post-papillectomy bleeding and were followed up until 12 months. The main outcomes were the delayed (≥24 h) post-papillectomy bleeding rate and the tumor persistence rate. RESULTS: The delayed post-papillectomy bleeding rate was 30.8% (8/26) in the prophylactic APC group and 21.4% (6/28) in the non-APC group (P = 0.434). The post-procedure pancreatitis rates were 23.1% (6/26) and 35.7% (10/28), respectively (P = 0.310). The rate of tumor persistence did not differ between the two groups at 1 month (12.5% vs 7.4%, P = 0.656), 3 months (4.2% vs 3.7%, P = 1.00), 6 months (8.3% vs 3.7%, P = 0.595), and 12 months (0% vs 3.7%, P = 1.00). There were no procedure-related mortalities or serious complications. CONCLUSION: Prophylactic APC may not be effective in reducing delayed post-papillectomy bleeding or remnant tumor ablation immediately after conventional papillectomy (Clinical trial registration-cris.nih.go.kr; KCT0001955).

Effects of molecular shape on alcohol aggregation and water hydrogen bond network behavior in butanol isomer solutions.

Despite butanol isomers such as n-butanol, sec-butanol, isobutanol and tert-butanol having the same chemical formula, their liquid-liquid phase diagrams are distinct. That is, tert-butanol is miscible in water at all concentrations, while the other three butanol isomers are partially miscible under ambient conditions. The molecular shape of tert-butanol is close to globular and differs from the other three butanol molecules with a relatively long carbon chain. By performing molecular dynamics simulations and graph theoretical analysis of the four water-butanol isomer mixtures at varying concentrations, we show how distinct butanol aggregates are formed which depend upon the molecular shape and affect the water H-bond network structure and phase diagram in the binary liquid. The three butanol isomers of n-butanol, sec-butanol and isobutanol at concentrated solutions form chain-like alcohol aggregates, but tert-butanol forms small aggregates due to the distinct packing behavior caused by its globular molecular shape. By employing the graph theoretical analysis such as the degree distribution and the eigenvalue spectrum from the adjacency matrix in the graphical representation of the alcohol H-bond network, we show that the tert-butanol aggregates have a different morphological structure from that of the other three butanol isomers in aqueous solution. The graph theoretically distinct butanol aggregates are categorized into two groups, water-compatible and water-incompatible, depending upon the interaction between the alcohol and water molecules. Based upon our observations, we propose that the water-incompatible networks of n-butanol, sec-butanol and isobutanol aggregates do not change the water structure significantly, forming two separate liquid phases that are alcohol-rich and water-rich. However, the water-compatible network of tert-butanol aggregates has a considerable interaction with the water molecules and causes significant disruption of the water H-bond network, forming a homogeneous solution. Understanding the alcohol aggregation behavior and water structure in butanol-water mixtures provides a critical clue in appreciating fundamental issues such as miscibility and phase separation in aqueous solution systems.

Understanding alcohol aggregates and the water hydrogen bond network towards miscibility in alcohol solutions: graph theoretical analysis.

Under ambient conditions, methanol and ethanol are miscible in water at all concentrations, while n-butanol is partially miscible. This is the first study to quantitatively examine the miscibility of butanol and compare with miscible alcohols by employing molecular dynamics simulations and graph theoretical analysis of three water-alcohol mixtures at various concentrations. We show how distinct alcohol aggregates are formed, thereby affecting the water structure, which established the relationship between the morphological structure of the aggregates and the miscibility of the alcohol in aqueous solution. The aggregates of methanol and ethanol in highly concentrated solutions form an extended H-bond network that intertwines well with the H-bond network of water. n-Butanol tends to self-associate and form large aggregates, while such aggregates are segregated from water. Graph theoretical analysis revealed that the alcohol aggregates of methanol and ethanol solutions have a morphological structure different from that of n-butanol, although there is no significant difference in morphology between the three pure alcohols. These two distinct alcohol aggregates are classified as water-compatible and water-incompatible depending upon their interaction with the water H-bond network, and their effect on the water structure was investigated. Our study reveals that the water-compatible network of alcohol aggregates in methanol and ethanol solutions disrupts the water H-bond networks, while the water-incompatible network of n-butanol aggregates does not considerably alter the water structure, which is consistent with the experimental results. Furthermore, we propose that miscible alcohols form water-compatible networks in binary aqueous systems while partially miscible alcohols form water-incompatible networks. The bifurcating hypothesis on the alcohol aggregation behavior in liquid water is of critical use to understand the fundamental issues such as solubility and phase separation in solution systems.