Gray matters: ViT-GAN framework for identifying schizophrenia biomarkers linking structural MRI and functional network connectivity.

Brain disorders are often associated with changes in brain structure and function, where functional changes may be due to underlying structural variations. Gray matter (GM) volume segmentation from 3D structural MRI offers vital structural information for brain disorders like schizophrenia, as it encompasses essential brain tissues such as neuronal cell bodies, dendrites, and synapses, which are crucial for neural signal processing and transmission; changes in GM volume can thus indicate alterations in these tissues, reflecting underlying pathological conditions. In addition, the use of the ICA algorithm to transform high-dimensional fMRI data into functional network connectivity (FNC) matrices serves as an effective carrier of functional information. In our study, we introduce a new generative deep learning architecture, the conditional efficient vision transformer generative adversarial network (cEViT-GAN), which adeptly generates FNC matrices conditioned on GM to facilitate the exploration of potential connections between brain structure and function. We developed a new, lightweight self-attention mechanism for our ViT-based generator, enhancing the generation of refined attention maps critical for identifying structural biomarkers based on GM. Our approach not only generates high quality FNC matrices with a Pearson correlation of 0.74 compared to real FNC data, but also uses attention map technology to identify potential biomarkers in GM structure that could lead to functional abnormalities in schizophrenia patients. Visualization experiments within our study have highlighted these structural biomarkers, including the medial prefrontal cortex (mPFC), dorsolateral prefrontal cortex (DL-PFC), and cerebellum. In addition, through cross-domain analysis comparing generated and real FNC matrices, we have identified functional connections with the highest correlations to structural information, further validating the structure-function connections. This comprehensive analysis helps to understand the intricate relationship between brain structure and its functional manifestations, providing a more refined insight into the neurobiological research of schizophrenia.

A Novel Classification System of Renal Hilar Tumors for Surgical Guidance: Technique, Outcome, and Safety.

BACKGROUND: This study was designed to develop an innovative classification and guidance system for renal hilar tumors and to assess the safety and effectiveness of robot-assisted partial nephrectomy (RAPN) for managing such tumors. METHODS: A total of 179 patients undergoing RAPN for renal hilar tumors were retrospectively reviewed. A novel classification system with surgical techniques was introduced and the perioperative features, tumor characteristics, and the efficacy and safety of RAPN were compared within subgroups. RESULTS: We classified the tumors according to our novel system as follows: 131 Type I, 35 Type II, and 13 Type III. However, Type III had higher median R.E.N.A.L., PADUA, and ROADS scores compared with the others (all p < 0.001), indicating increased operative complexity and higher estimated blood loss [180.00 (115.00-215.00) ml]. Operative outcomes revealed significant disparities between Type III and the others, with longer operative times [165.00 (145.00-200.50) min], warm ischemia times [24.00 (21.50-30.50) min], tumor resection times [13.00 (12.00-15.50) min], and incision closure times [22.00 (20.00-23.50) min] (all p < 0.005). Postoperative outcomes also showed significant differences, with longer durations of drain removal (77.08 ± 18.16 h) and hospitalization for Type III [5.00 (5.00-6.00) d] (all p < 0.05). Additionally, Type I had a larger tumor diameter than the others (p = 0.009) and pT stage differed significantly between the subtypes (p = 0.020). CONCLUSIONS: The novel renal hilar tumor classification system is capable of differentiating the surgical difficulty of RAPN and further offers personalized surgical steps tailored to each specific classification. It provides a meaningful tool for clinical practice.

Associations between R.E.N.A.L. nephrometry score and survival outcomes in renal tumours.

OBJECTIVE: The radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry score could be used to predict surgical outcomes and renal tumour aggressiveness. We aimed to analyse its associations with survival outcomes. METHODS: We included 1368 patients with sporadic, unilateral and non-metastatic renal tumours who received curative nephrectomy in Zhongshan Hospital from January 2009 to September 2019. Radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry scores were assigned by three urologists based on preoperative CT/MRI scans. Correlations between parameters or sum of radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry scores, overall survival and recurrence-free survival were analysed by Kaplan-Meier analyses and the multivariate Cox regression model. We further compared survival outcomes between patients who received partial nephrectomy and patients who received radical nephrectomy. RESULTS: We observed statistically significant associations between all components of radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry scores and oncologic outcomes, including R (radius) (overall survival, P < 0.001; recurrence-free survival , P < 0.001), E (exophytic/endophytic) (overall survival, P = 0.003; recurrence-free survival, P < 0.001), N (nearness) (overall survival, P = 0.063; recurrence-free survival, P < 0.001), A (anterior/posterior) (overall survival, P < 0.001; recurrence-free survival, P = 0.005), L (location) (overall survival, P = 0.008; recurrence-free survival, P < 0.001) and suffix 'h' (overall survival, P = 0.237; recurrence-free survival, P = 0.034). Kaplan-Meier curves of overall survival and recurrence-free survival rates were significantly different when stratified by radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry score complexity group (overall survival, P < 0.001; recurrence-free survival, P < 0.001). After adjusting for tumour stage and grade, radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry score as continuous variables was an adverse independent risk factor for survival outcomes [P = 0.027, hazard ratio (95% confidence interval) = 1.151 (1.016-1.303)] and recurrence-free survival [P < 0.001, hazard ratio (95% confidence interval) = 1.299 (1.125-1.501)]. For tumours with radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry scores of 4 and 5, partial nephrectomy showed a survival benefit than radical nephrectomy. CONCLUSION: Both components and complexity groups of the radius-exophytic/endophytic-nearness-anterior/posterior-location nephrometry score are associated with survival outcomes in renal tumour patients.

Application of Multi-Channel Synchronized Dynamic Strain Gauges in Monitoring the Neutral Axis Position and Prestress Loss of Box Girder Bridges.

The aim of this paper was to explore the application of multi-channel synchronized dynamic strain gauges in monitoring the neutral axis (N.A.) position of prestressed concrete box girders. The N.A. position has recently been proposed as an indicator for monitoring the health of bridge structures. Laboratory experiments were conducted on a prestressed T-beam under different prestress level conditions to investigate the correlation between the prestress magnitude and the N.A. position. In the development of the multi-channel synchronized dynamic strain gauges, edge computing was employed to significantly reduce the amount of data transmitted from the sensor nodes on-site. In edge computing, only the dynamic strain response caused by the maximum vehicle load in each minute is transmitted. This approach greatly enhances the monitoring efficiency and enables the realization of on-site non-computer-based monitoring systems. The laboratory test results of the prestressed T-beam showed that the N.A. position tends to move slightly downward as the prestress force increases. In other words, when the prestress force decreases due to loss, the N.A. position exhibits a slight upward movement. This study selected a newly constructed prestressed box girder as the subject for on-site measurement of the N.A. position using multi-channel synchronized dynamic strain gauges shortly after the prestress was applied. The on-site monitoring data indeed revealed a gradual upward movement of the N.A. position. This phenomenon confirmed that soon after the completion of prestressed concrete bridges, there is a gradual loss of prestress due to the significant shrinkage and creep effects of the early-age concrete. The on-site monitoring result aligned with the findings from the laboratory experiments, where the N.A. position was observed to move upward as the prestress decreased.

[The last illness of I.S. Turgenev].

The article discusses the causes and course of the last illness of I.S. Turgenev. The writer was consulted by many famous French and Russian doctors who made various diagnoses and used various methods of treatment. The primary disease that caused Turgenev's death is myxosarcoma (one of the sarcoma variants), involving soft tissues and thoracic vertebrae. The article presents data and discusses alternative diagnostic versions about the nature of the disease and the causes of death of the great Russian writer.

Halogen-Bonded Organic Frameworks (XOFs) Based on N⋠⋠⋠Br+⋠⋠⋠N Bonds: Robust Organic Networks Constructed by Fragile Bonds.

Organic frameworks face a trade-off between the framework stability and the bond dynamics, which necessitates the development of innovative linkages that can generate stable frameworks without hindering efficient synthesis. Although iodine(I)-based halogen-bonded organic frameworks (XOFs) have been developed, constructing XOFs based on bromine(I) is desirable yet challenging due to the high sensitivity of bromine(I) species. In this work, we present the inaugural construction of stable bromine(I)-bridged two-dimensional (2D) halogen-bonded organic frameworks, XOF(Br)-TPy-BF4/OTf, based on sensitive [N⋅⋅⋅Br⋅⋅⋅N]+ halogen bonds. The formation of XOF(Br)-TPy-BF4/OTf was monitored by 1H NMR, XPS, IR, SEM, TEM, HR-TEM, SEAD. Their framework structures were established by the results from PXRD, theoretical simulations and SAXS. More importantly, XOF(Br) displayed excellent chemical and thermal stabilities. They exhibited stable two-dimensional framework structures in various organic solvents and aqueous media, even over a wide pH range (pH 3-12), while the corresponding model compounds BrPy2BF4/OTf decomposed quickly even in the presence of minimal water. Furthermore, the influence of the counterions were investigated by replacing BF4 with OTf, which improved the stability of XOF(Br). This characteristic enabled XOF(Br) to serve as an efficient oxidizing reagent in aqueous environments, in contrast with the sensitivity of BrPy2BF4/OTf, which performed well only in organic media. This study not only deepens our fundamental understanding of organic frameworks but also opens new avenues for the development and application of multifunctional XOFs.

Impact of tumor contact surface area on collecting system entry in robot-assisted partial nephrectomy: a retrospective analysis.

BACKGROUND: Collecting system entry in robot-assisted partial nephrectomy may occur even in cases showing a low N factor in the R.E.N.A.L nephrometry score. Therefore, in this study, we focused on the tumor contact surface area with the adjacent renal parenchyma and attempted to construct a novel predictive model for collecting system entry. METHODS: Among 190 patients who underwent robot-assisted partial nephrectomy at our institution from 2015 to 2021, 94 patients with a low N factor (1-2) were analyzed. Contact surface was measured with three-dimensional imaging software and defined as the C factor, classified as C1, < 10 cm [2]; C2, ≥ 10 and < 15 cm [2]; and C3: ≥ 15 cm [2]. Additionally, a modified R factor (mR) was classified as mR1, < 20 mm; mR2, ≥ 20 and < 40 mm; and mR3, ≥ 40 mm. We discussed the factors influencing collecting system entry, including the C factor, and created a novel collecting system entry predictive model. RESULTS: Collecting system entry was observed in 32 patients with a low N factor (34%). The C factor was the only independent predictive factor for collecting system entry in multivariate regression analysis (odds ratio: 4.195, 95% CI: 2.160-8.146, p < 0.0001). Models including the C factor showed better discriminative power than the models without the C factor. CONCLUSIONS: The new predictive model, including the C factor in N1-2 cases, may be beneficial, considering its indication for preoperative ureteral catheter placement in patients undergoing robot-assisted partial nephrectomy.

[Activity of N.A. Semashko during the evacuation of the 1st Moscow Order of Lenin Medical Institute to Ufa (1941-1942)].

An attempt is made to systematize the main directions of N.A. Semashko's activity during the evacuation of the 1st Moscow Order of Lenin Medical Institute (MOLMI) during the Great Patriotic War to Ufa (October 1941 - March 1942) is undertaken. The significance of its results for the Bashkir State Medical Institute (now Bashkir State Medical University) is evaluated. It is shown that the joint work of N.A. Semashko with the teaching staff of the 1st MOLMI and Bashkir medical institute improved the pedagogical and scientific qualification of teachers at Bashkir medical institute, improved the existing forms of teaching, scientific and educational work during the period of war and created new ones. Professor N.A. Semashko actively worked in several directions during complicated conditions of evacuation. Besides pedagogical and scientific activities, he was occupied with the training of scientific-pedagogical personnel, took part in advanced training of physicians and medical workers, organized educational work with the population, delivered brilliant lectures to the crowded halls. In addition, as the first People's Commissar of Health of the RSFSR, he helped the People's Commissariat of Health of the Bashkir ASSR in organizing the work of evacuation hospitals and rendering assistance to health care institutions located on the territory of the Bashkir ASSR.

[WORLD EXPERIENCE: HOW THE DEVELOPMENT OF THE PRINCIPLES OF ACADEMICIAN OF THE ACADEMY OF MEDICAL SCIENCES OF THE USSR N. A. SEMASHKO HELPED ICELAND TO CREATE ONE OF THE MOST EFFECTIVE HEALTHCARE SYSTEMS IN THE WORLD. PART 1. HISTORICAL OVERVIEW].

Annotation. The review article is devoted to the healthcare system of Iceland, which demonstrates some of the best indicators of public health in the world at relatively low costs for a developed European country. The successful experience of Icelandic healthcare is important for Russia, on the one hand, due to the proximity of this country to many Russian regions in terms of climatic and geographical location, demography and territorial development. On the other hand, the success of Iceland's healthcare is closely linked to the development of a model, in many ways similar to the Soviet model of Nikolai Semashko, which Russia has abandoned. The authors believe that Iceland's experience can be used in the modernization of regional healthcare systems in Eastern Siberia, the Far East and the Arctic, as well as Russian healthcare in general.

[WORLD EXPERIENCE: HOW THE DEVELOPMENT OF THE PRINCIPLES OF ACADEMICIAN OF THE ACADEMY OF MEDICAL SCIENCES OF THE USSR N. A. SEMASHKO HELPED ICELAND TO CREATE ONE OF THE MOST EFFECTIVE HEALTHCARE SYSTEMS IN THE WORLD. PART 2. PRINCIPLES FUNCTIONING OF THE ICELANDIC HEALTH SYSTEM].

Annotation. The review article is devoted to the healthcare system of Iceland, which demonstrates some of the best indicators of public health in the world at relatively low costs for a developed European country. The successful experience of Icelandic healthcare is important for Russia, on the one hand, due to the proximity of this country to many Russian regions in terms of climatic and geographical location, demography and territorial development. On the other hand, the success of Iceland's healthcare is closely linked to the development of a model, in many ways similar to the Soviet model of Nikolai Semashko, which Russia has abandoned. The authors believe that Iceland's experience can be used in the modernization of regional healthcare systems in Eastern Siberia, the Far East and the Arctic, as well as Russian healthcare in general.

[Clinical case conference in medical practice and education: Origins and current status].

A genesis of clinical case conference as a form of case discussion that integrates medical and educational functions is presented. The role of the following top figures of medicine in the development of clinical case conference is described: J.-M. Charcot, S.P. Botkin, G.A. Zakharin, V.N. Vinogradov, A.L. Myasnikov, E.M. Tareev, N.A. Mukhin. The article pays special attention to clinical case conference in Russian medical education. The role of clinical case conferences in shaping medical judgment in a clinician and a student is discussed.

Clinical implications of 3D printing technology in preoperative evaluation of partial nephrectomy. / 3D打印技术应用于肾部分切除术术前评估中的临床意义.

OBJECTIVES: Renal cancer is a common malignancy of the urinary system, and the partial nephrectomy is a common surgical modality for early renal cancer. 3D printing technology can create a visual three-dimensional model by using 3D digital models of the patient's imaging data. With this model, surgeons can perform preoperative assessment to clarify the location, depth, and blood supply of the tumor, which helps to develop preoperative plans and achieve better surgical outcomes. In this study, the R.E.N.A.L scoring system was used to stratify patients with renal tumors and to explore the clinical application value of 3D printing technology in laparoscopic partial nephrectomy. METHODS: A total of 114 renal cancer patients who received laparoscopic partial nephrectomy in Xiangya Hospital from June 2019 to December 2020 were enrolled. The patients were assigned into an experimental group (n=52) and a control group (n=62) according to whether 3D printing technology was performed, and the differences in perioperative parameters between the 2 groups were compared. Thirty-nine patients were assigned into a low-complexity group (4-6 points), 32 into a moderate-complexity group (7-9 points), and 43 into a high-complexity group (10-12 points) according to R.E.N.A.L score, and the differences in perioperative parameters between the experimental group and the control group in each score group were compared. RESULTS: The experimental group had shorter operative time, renal ischemia time, and postoperative hospital stay (all P<0.05), less intraoperative blood loss (P=0.047), and smaller postoperative blood creatinine change (P=0.032) compared with the control group. In the low-complexity group, there were no statistically significant differences between the experimental group and the control group in operation time, renal ischemia time, intraoperative blood loss, postoperative blood creatinine changes, and postoperative hospital stay (all P>0.05). In the moderate- and high- complexity groups, the experimental group had shorter operative time, renal ischemia time, and postoperative hospital stay (P<0.05 or P<0.001), less intraoperative blood loss (P=0.022 and P<0.001, respectively), and smaller postoperative blood creatinine changes (P<0.05 and P<0.001, respectively) compared with the control group. CONCLUSIONS: Compared with renal tumor patients with R.E.N.A.L score<7, renal cancer patients with R.E.N.A.L score≥7 may benefit more from 3D printing assessment before undergoing partial nephrectomy.

[Urological complications of N.A. Nekrasovs disease].

OBJECT: to study the medical history of N.A. Nekrasov and to determine the nature of his urological disease. The work was carried out from 1977 till 2021. He studied 2616 sources related to the biography of N.A. Nekrasov and medical history. The work was carried out in the archives of Moscow, St.Petersburg, Yaroslavl, Karabikha from 1998 till 2020. The Russian poet N.A.Nekrasov had an illness, which ended in death, during 3 years, from December 1874 till December 27, 1877. He was treated by famous doctors S.P. Botkin, N.V. Sklifosovsky, E.I. Bogdanovsky, N.A. Belogolovy and an operation was performed by Theodore Bilroth. Retrospective analysis revealed the following diagnosis of N.A. Nekrasov: rectal cancer at the stage of T4NXMOP4 with invasion of the sacrum, bladder and compression of the pelvic parts of both ureters, bilateral ureterohydronephrosis with the loss of the left kidney function, chronic renal failure, purulent cystitis, partial intestinal obstruction, suppuration of the wound after colostomy performed on April 12, 1877, Acute purulent paraproctitis, paranephritis, phlegmon of the left retroperitoneal space, purulent effusion to the thigh, phlegmon of the buttock area and the left thigh, sepsis, cerebral stroke. Urological complications of the rectal cancer accelerated the lethal outcome of the poet N.A. Nekrasov who died of sepsis and uremia.

["The letters of S. P. Botkin from Bulgaria. 1877": The history of publication of autograph].

The letters of S. P. Botkin from Bulgaria (1877) to his wife, E. A. Botkina (née Princess Obolenskaya), were published as travel diary in the journal "Vestnik Evropy" in 1892 and as separate book in 1893. The family events related to publication of epistolary were restored. For publication, material of private nature was abridged by E. A. Botkina. Then, passages with compromising criticism were removed by editor of the journal. In spite of good quality of prepared text, publication was postponed by E. A. Botkina herself and afterwards it was lingered on because of claims of censorial department. The role of N. A. Belogolovy, public figure and friend of S. P. Botkin of many years and M. M. Stasyulevich, a publisher, in final decision to publish epistolary is emphasized. The comparison of original and printed matter carried out for the first time, established that cuts made up to more than one third of author's text.

[The first steps of the Zemstvo sanitary inspector N. A. Semashko in fight with epidemics in the Novouzensk Uyezd of the Samara Guberniya].

The personality of N. A. Semashko presents incontestable interest as health care official and ideologist of the Soviet health care system who contributed significantly into development of health care. Great number of studies are devoted to analysis of activities of N. A. Semashko in the Soviet period holding position of the First People's Commissar of health care of the RSFSR, initiator and head of the chair of Social hygiene of the Medical Faculty of the First Moscow State University. The studies related to pre-revolutionary period of life of N. A. Semashko are presented in less degree. The article describes, on the basis of publications and archive sources (documents from the Central State Archive of the Samara Oblast, the foundations of the Russian State Library and also the family archive of E. G. Farobina, grand-daughter of N. A. Semashko) the period of life and and activity of N. A. Semashko in the Samara Gubernia after graduating the medical faculty of the Imperial Kazan University. In 1901-1902, after short training in bacteriological laboratory of the Samara Gubernia Zemstvo Hospital and appointment to the post of sanitary and epidemiological doctor of the Zemstvo, N. A. Semashko was directly involved in elimination of epidemics of diphtheria in Orlov Guy village and of anthrax in Alexandria village of the Novouzensky Uezd. The dangerous epidemics were eliminated owing to outstanding medical knowledge, courage and organizational skills of young doctor.

"The letters of S. P. Botkin from Bulgaria. 1887": The return of the manuscript in Russia.

The previous report partially brought to light history of publishing of "The letters of S. P. Botkin from Bulgaria 1877". The original letters were abroad for many years and they were returned to the USSR in 1974 by grandchildren of S. P. Botkin, S. P. Chekhov and D. P. Chekhov, who resided in France. The circumstances of handing over of the letters to the N. A. Semashko Institute of Health Organization and Social Hygiene are presented. The letters have not been republished for 130 years, but their historical, moral and educational significance remains actual and nowadays. The modern edition of the complete manuscript, along with introductory article and detailed scientific commentary, will become a significant contribution to representation of biography of S.P Botkin, to supplementation of written sources about the Russian-Turkish war of 1877-1878, and to comprehension of centuries-old Middle Eastern geopolitics of Russia.

Conservative management of patients with endometrial intraepithelial neoplasia (EIN): Factors that could affect response and pregnancy rates.

N/A.

Halogen-Bonded Organic Framework (XOF) Based on Iodonium-Bridged N⋠⋠⋠I+ ⋠⋠⋠N Interactions: A Type of Diphase Periodic Organic Network.

Due to the fascinating structures and wide applications, porous materials with open frameworks have attracted more and more attentions. Herein, a novel two-dimensional (2D) halogen-bonded organic framework (XOF-TPPE) was successfully designed and fabricated by iodonium-bridged N⋅⋅⋅I+ ⋅⋅⋅N interactions between pyridyl groups and I+ for the first time. The formation of XOF-TPPE and its linear analogue was monitored by 1 H NMR, UV-Vis, X-ray photoelectron spectroscopy (XPS), IR, SEM, TEM, HRTEM and selected-area electron diffraction (SAED). The structural model of XOF-TPPE was established based on powder X-ray diffraction (PXRD) data and theoretical simulations. Significantly, synchrotron small-angle X-ray scattering (SAXS), DLS and UV-Vis spectroscopy experiments suggested that XOF-TPPE still maintains a stable 2D framework structure in solutions. This research opens up a novel avenue for the development of organic frameworks materials, and may bring new promising applications for the field of porous materials.

In vitro characterization of N-terminal truncated EpsC from Bacillus subtilis 168, a UDP-N-acetylglucosamine 4,6-dehydratase.

Bacillus subtilis 168 EpsC is annotated as "Probable polysaccharide biosynthesis protein" in the SwissProt database. epsC is part of the eps operon, thought to be involved in the biosynthesis of exopolymeric substances (EPS). The present study was undertaken to determine the molecular function of EpsC. Sequence analysis of EpsC suggested the presence of a transmembrane domain. Two N-terminal deletion mutants in which residues 1-89 (EpsC89) and 1-115 (EpsC115) are deleted were cloned and overexpressed. Enzyme activity and substrate preferences were investigated by reverse phase HPLC, surface plasmon resonance (SPR) spectroscopy and absorption spectroscopy. These data show that EpsC has UDP-GlcNAc 4,6-dehydratase activity in vitro. Purified recombinant proteins were found to utilise UDP-Glc and TDP-Glc also as substrates. In addition, EpsC115 could utilise UDP-Gal and UDP-GalNAc as substrates whereas EpsC89 could only bind these two sugar nucleotides. These results show that deletion of a longer N-terminal region broadens substrate specificity. These broadened specificity is perhaps an outcome of the deletion of the putative transmembrane domain and may not be present in vivo. EpsC, together with the aminotransferase EpsN (Kaundinya CR et al., Glycobiology, 2018) and acetyltransferase EpsM (unpublished data), appears to be involved in the biosynthesis of N,N'-diacetylbacillosamine.

Thioamide substitution to probe the hydroxyproline recognition of VHL ligands.

Thioamide substitution influences hydrogen bond and n → π∗ interactions involved in the conformational stability of protein secondary structures and oligopeptides. Hydroxyproline is the key recognition element of small molecules targeting the von Hippel-Lindau (VHL) E3 ligase, which are of interest as probes of hypoxia signaling and ligands for PROTAC conjugation. We hypothesized that VHL ligands could be a privileged model system to evaluate the contribution of these interactions to protein:ligand complex formation. Herein we report the synthesis of VHL ligands bearing thioamide substitutions at the central hydroxyproline moiety, and characterize their binding by fluorescence polarization, isothermal titration calorimetry, X-ray crystallography and molecular modeling. In spite of a conserved binding mode, the substitution pattern had a pronounced impact on the ligand affinities. Together the results underscore the role of hydrogen bond and n → π∗ interactions in fine tuning hydroxyproline recognition by VHL.