De novo drug design through artificial intelligence: an introduction

Developing new drugs is a complex and formidable challenge, intensified by rapidly evolving global health needs. De novo drug design is a promising strategy to accelerate and refine this process. The recent introduction of Generative Artificial Intelligence (AI) algorithms has brought new attention to the field and catalyzed a paradigm shift, allowing rapid and semi-automatic design and optimization of drug-like molecules. This review explores the impact of de novo drug design, highlighting both traditional methodologies and the recently introduced generative algorithms, as well as the promising development of Active Learning (AL). It places special emphasis on their application in oncological drug development, where the need for novel therapeutic agents is urgent. The potential integration of these AI technologies with established computational and experimental methods heralds a new era in the rapid development of innovative drugs. Despite the promising developments and notable successes, these technologies are not without limitations, which require careful consideration and further advancement. This review, intended for professionals across related disciplines, provides a comprehensive introduction to AI-driven de novo drug design of small organic molecules. It aims to offer a clear understanding of the current state and future prospects of these innovative techniques in drug discovery

The miniJPAS survey: a preview of the Universe in 56 colours

International audienceThe Javalambre-Physics of the Accelerating Universe Astrophysical Survey (J-PAS) will soon start to scan thousands of square degrees of the northern extragalactic sky with a unique set of $56$ optical filters from a dedicated $2.55$m telescope, JST, at the Javalambre Astrophysical Observatory. Before the arrival of the final instrument (a 1.2 Gpixels, 4.2deg$^2$ field-of-view camera), the JST was equipped with an interim camera (JPAS-Pathfinder), composed of one CCD with a 0.3deg$^2$ field-of-view and resolution of 0.23 arcsec pixel$^{-1}$. To demonstrate the scientific potential of J-PAS, with the JPAS-Pathfinder camera we carried out a survey on the AEGIS field (along the Extended Groth Strip), dubbed miniJPAS. We observed a total of $\sim 1$ deg$^2$, with the $56$ J-PAS filters, which include $54$ narrow band (NB, $\rm{FWHM} \sim 145$Angstrom) and two broader filters extending to the UV and the near-infrared, complemented by the $u,g,r,i$ SDSS broad band (BB) filters. In this paper we present the miniJPAS data set, the details of the catalogues and data access, and illustrate the scientific potential of our multi-band data. The data surpass the target depths originally planned for J-PAS, reaching $\rm{mag}_{\rm {AB}}$ between $\sim 22$ and $23.5$ for the NB filters and up to $24$ for the BB filters ($5\sigma$ in a $3$~arcsec aperture). The miniJPAS primary catalogue contains more than $64,000$ sources extracted in the $r$ detection band with forced photometry in all other bands. We estimate the catalogue to be complete up to $r=23.6$ for point-like sources and up to $r=22.7$ for extended sources. Photometric redshifts reach subpercent precision for all sources up to $r=22.5$, and a precision of $\sim 0.3$% for about half of the sample. (Abridged

The miniJPAS survey: A preview of the Universe in 56 colors

International audienceThe Javalambre-Physics of the Accelerating Universe Astrophysical Survey (J-PAS) will scan thousands of square degrees of the northern sky with a unique set of 56 filters using the dedicated 2.55 m Javalambre Survey Telescope (JST) at the Javalambre Astrophysical Observatory. Prior to the installation of the main camera (4.2 deg2 field-of-view with 1.2 Gpixels), the JST was equipped with the JPAS-Pathfinder, a one CCD camera with a 0.3 deg2 field-of-view and plate scale of 0.23 arcsec pixel−1. To demonstrate the scientific potential of J-PAS, the JPAS-Pathfinder camera was used to perform miniJPAS, a ∼1 deg2 survey of the AEGIS field (along the Extended Groth Strip). The field was observed with the 56 J-PAS filters, which include 54 narrow band (FWHM ∼ 145 Å) and two broader filters extending to the UV and the near-infrared, complemented by the u, g, r, i SDSS broad band filters. In this miniJPAS survey overview paper, we present the miniJPAS data set (images and catalogs), as we highlight key aspects and applications of these unique spectro-photometric data and describe how to access the public data products. The data parameters reach depths of magAB ≃ 22−23.5 in the 54 narrow band filters and up to 24 in the broader filters (5σ in a 3″ aperture). The miniJPAS primary catalog contains more than 64 000 sources detected in the r band and with matched photometry in all other bands. This catalog is 99% complete at r = 23.6 (r = 22.7) mag for point-like (extended) sources. We show that our photometric redshifts have an accuracy better than 1% for all sources up to r = 22.5, and a precision of ≤0.3% for a subset consisting of about half of the sample. On this basis, we outline several scientific applications of our data, including the study of spatially-resolved stellar populations of nearby galaxies, the analysis of the large scale structure up to z ∼ 0.9, and the detection of large numbers of clusters and groups. Sub-percent redshift precision can also be reached for quasars, allowing for the study of the large-scale structure to be pushed to z > 2. The miniJPAS survey demonstrates the capability of the J-PAS filter system to accurately characterize a broad variety of sources and paves the way for the upcoming arrival of J-PAS, which will multiply this data by three orders of magnitude.Key words: surveys / techniques: photometric / astronomical databases: miscellaneous / stars: general / galaxies: general / cosmology: observations⋆ miniJPAS data and associated value added catalogs are publicly available http://archive.cefca.es/catalogues/minijpas-pdr20191

The miniJPAS survey: A preview of the Universe in 56 colors

The Javalambre-Physics of the Accelerating Universe Astrophysical Survey (J-PAS) will scan thousands of square degrees of the northern sky with a unique set of 56 filters using the dedicated 2.55 m Javalambre Survey Telescope (JST) at the Javalambre Astrophysical Observatory. Prior to the installation of the main camera (4.2 deg2 field-of-view with 1.2 Gpixels), the JST was equipped with the JPAS-Pathfinder, a one CCD camera with a 0.3 deg2 field-of-view and plate scale of 0.23 arcsec pixel−1. To demonstrate the scientific potential of J-PAS, the JPAS-Pathfinder camera was used to perform miniJPAS, a ∼1 deg2 survey of the AEGIS field (along the Extended Groth Strip). The field was observed with the 56 J-PAS filters, which include 54 narrow band (FWHM ∼ 145 Å) and two broader filters extending to the UV and the near-infrared, complemented by the u, g, r, i SDSS broad band filters. In this miniJPAS survey overview paper, we present the miniJPAS data set (images and catalogs), as we highlight key aspects and applications of these unique spectro-photometric data and describe how to access the public data products. The data parameters reach depths of magAB ≃ 22−23.5 in the 54 narrow band filters and up to 24 in the broader filters (5σ in a 3″ aperture). The miniJPAS primary catalog contains more than 64 000 sources detected in the r band and with matched photometry in all other bands. This catalog is 99% complete at r = 23.6 (r = 22.7) mag for point-like (extended) sources. We show that our photometric redshifts have an accuracy better than 1% for all sources up to r = 22.5, and a precision of ≤0.3% for a subset consisting of about half of the sample. On this basis, we outline several scientific applications of our data, including the study of spatially-resolved stellar populations of nearby galaxies, the analysis of the large scale structure up to z ∼ 0.9, and the detection of large numbers of clusters and groups. Sub-percent redshift precision can also be reached for quasars, allowing for the study of the large-scale structure to be pushed to z > 2. The miniJPAS survey demonstrates the capability of the J-PAS filter system to accurately characterize a broad variety of sources and paves the way for the upcoming arrival of J-PAS, which will multiply this data by three orders of magnitude

An international assessment of the adoption of enhanced recovery after surgery (ERAS®) principles across colorectal units in 2019–2020

AimThe Enhanced Recovery After Surgery (ERAS®) Society guidelines aim to standardize perioperative care in colorectal surgery via 25 principles. We aimed to assess the variation in uptake of these principles across an international network of colorectal units.MethodAn online survey was circulated amongst European Society of Coloproctology members in 2019–2020. For each ERAS principle, respondents were asked to score how frequently the principle was implemented in their hospital, from 1 (‘rarely’) to 4 (‘always’). Respondents were also asked to recall whether practice had changed since 2017. Subgroup analyses based on hospital characteristics were conducted.ResultsOf hospitals approached, 58% responded to the survey (195/335), with 296 individual responses (multiple responses were received from some hospitals). The majority were European (163/195, 83.6%). Overall, respondents indicated they ‘most often’ or ‘always’ adhered to most individual ERAS principles (18/25, 72%). Variability in the uptake of principles was reported, with universal uptake of some principles (e.g., prophylactic antibiotics; early mobilization) and inconsistency from ‘rarely’ to ‘always’ in others (e.g., no nasogastric intubation; no preoperative fasting and carbohydrate drinks). In alignment with 2018 ERAS guideline updates, adherence to principles for prehabilitation, managing anaemia and postoperative nutrition appears to have increased since 2017.ConclusionsUptake of ERAS principles varied across hospitals, and not all 25 principles were equally adhered to. Whilst some principles exhibited a high level of acceptance, others had a wide variability in uptake indicative of controversy or barriers to uptake. Further research into specific principles is required to improve ERAS implementation.AimThe Enhanced Recovery After Surgery (ERAS®) Society guidelines aim to standardize perioperative care in colorectal surgery via 25 principles. We aimed to assess the variation in uptake of these principles across an international network of colorectal units.MethodAn online survey was circulated amongst European Society of Coloproctology members in 2019–2020. For each ERAS principle, respondents were asked to score how frequently the principle was implemented in their hospital, from 1 (‘rarely’) to 4 (‘always’). Respondents were also asked to recall whether practice had changed since 2017. Subgroup analyses based on hospital characteristics were conducted.ResultsOf hospitals approached, 58% responded to the survey (195/335), with 296 individual responses (multiple responses were received from some hospitals). The majority were European (163/195, 83.6%). Overall, respondents indicated they ‘most often’ or ‘always’ adhered to most individual ERAS principles (18/25, 72%). Variability in the uptake of principles was reported, with universal uptake of some principles (e.g., prophylactic antibiotics; early mobilization) and inconsistency from ‘rarely’ to ‘always’ in others (e.g., no nasogastric intubation; no preoperative fasting and carbohydrate drinks). In alignment with 2018 ERAS guideline updates, adherence to principles for prehabilitation, managing anaemia and postoperative nutrition appears to have increased since 2017.ConclusionsUptake of ERAS principles varied across hospitals, and not all 25 principles were equally adhered to. Whilst some principles exhibited a high level of acceptance, others had a wide variability in uptake indicative of controversy or barriers to uptake. Further research into specific principles is required to improve ERAS implementation.A

Association of mechanical bowel preparation with oral antibiotics and anastomotic leak following left sided colorectal resection: an international, multi-centre, prospective audit.

This is the peer reviewed version of the following article: , (2018), Association of mechanical bowel preparation with oral antibiotics and anastomotic leak following left sided colorectal resection: an international, multi‐centre, prospective audit. Colorectal Dis, 20: 15-32. doi:10.1111/codi.14362, which has been published in final form at https://doi.org/10.1111/codi.14362. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsINTRODUCTION: The optimal bowel preparation strategy to minimise the risk of anastomotic leak is yet to be determined. This study aimed to determine whether oral antibiotics combined with mechanical bowel preparation (MBP+Abx) was associated with a reduced risk of anastomotic leak when compared to mechanical bowel preparation alone (MBP) or no bowel preparation (NBP). METHODS: A pre-planned analysis of the European Society of Coloproctology (ESCP) 2017 Left Sided Colorectal Resection audit was performed. Patients undergoing elective left sided colonic or rectal resection with primary anastomosis between 1 January 2017 and 15 March 2017 by any operative approach were included. The primary outcome measure was anastomotic leak. RESULTS: Of 3676 patients across 343 centres in 47 countries, 618 (16.8%) received MBP+ABx, 1945 MBP (52.9%) and 1099 patients NBP (29.9%). Patients undergoing MBP+ABx had the lowest overall rate of anastomotic leak (6.1%, 9.2%, 8.7% respectively) in unadjusted analysis. After case-mix adjustment using a mixed-effects multivariable regression model, MBP+Abx was associated with a lower risk of anastomotic leak (OR 0.52, 0.30-0.92, P = 0.02) but MBP was not (OR 0.92, 0.63-1.36, P = 0.69) compared to NBP. CONCLUSION: This non-randomised study adds 'real-world', contemporaneous, and prospective evidence of the beneficial effects of combined mechanical bowel preparation and oral antibiotics in the prevention of anastomotic leak following left sided colorectal resection across diverse settings. We have also demonstrated limited uptake of this strategy in current international colorectal practice

An international assessment of the adoption of enhanced recovery after surgery (ERAS®) principles across colorectal units in 2019–2020

Aim: The Enhanced Recovery After Surgery (ERAS®) Society guidelines aim to standardize perioperative care in colorectal surgery via 25 principles. We aimed to assess the variation in uptake of these principles across an international network of colorectal units. Method: An online survey was circulated amongst European Society of Coloproctology members in 2019–2020. For each ERAS principle, respondents were asked to score how frequently the principle was implemented in their hospital, from 1 (‘rarely’) to 4 (‘always’). Respondents were also asked to recall whether practice had changed since 2017. Subgroup analyses based on hospital characteristics were conducted. Results: Of hospitals approached, 58% responded to the survey (195/335), with 296 individual responses (multiple responses were received from some hospitals). The majority were European (163/195, 83.6%). Overall, respondents indicated they ‘most often’ or ‘always’ adhered to most individual ERAS principles (18/25, 72%). Variability in the uptake of principles was reported, with universal uptake of some principles (e.g., prophylactic antibiotics; early mobilization) and inconsistency from ‘rarely’ to ‘always’ in others (e.g., no nasogastric intubation; no preoperative fasting and carbohydrate drinks). In alignment with 2018 ERAS guideline updates, adherence to principles for prehabilitation, managing anaemia and postoperative nutrition appears to have increased since 2017. Conclusions: Uptake of ERAS principles varied across hospitals, and not all 25 principles were equally adhered to. Whilst some principles exhibited a high level of acceptance, others had a wide variability in uptake indicative of controversy or barriers to uptake. Further research into specific principles is required to improve ERAS implementation

Safety of primary anastomosis following emergency left sided colorectal resection: an international, multi-centre prospective audit.

This is the peer reviewed version of the following article: group, T. E. S. o. C. c. (2018). "Safety of primary anastomosis following emergency left sided colorectal resection: an international, multi-centre prospective audit." Colorectal Disease 20(S6): 47-57., which has been published in final form at https://doi.org/10.1111/codi.1437. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsINTRODUCTION: Some evidence suggests that primary anastomosis following left sided colorectal resection in the emergency setting may be safe in selected patients, and confer favourable outcomes to permanent enterostomy. The aim of this study was to compare the major postoperative complication rate in patients undergoing end stoma vs primary anastomosis following emergency left sided colorectal resection. METHODS: A pre-planned analysis of the European Society of Coloproctology 2017 audit. Adult patients (> 16 years) who underwent emergency (unplanned, within 24 h of hospital admission) left sided colonic or rectal resection were included. The primary endpoint was the 30-day major complication rate (Clavien-Dindo grade 3 to 5). RESULTS: From 591 patients, 455 (77%) received an end stoma, 103 a primary anastomosis (17%) and 33 primary anastomosis with defunctioning stoma (6%). In multivariable models, anastomosis was associated with a similar major complication rate to end stoma (adjusted odds ratio for end stoma 1.52, 95%CI 0.83-2.79, P = 0.173). Although a defunctioning stoma was not associated with reduced anastomotic leak (12% defunctioned [4/33] vs 13% not defunctioned [13/97], adjusted odds ratio 2.19, 95%CI 0.43-11.02, P = 0.343), it was associated with less severe complications (75% [3/4] with defunctioning stoma, 86.7% anastomosis only [13/15]), a lower mortality rate (0% [0/4] vs 20% [3/15]), and fewer reoperations (50% [2/4] vs 73% [11/15]) when a leak did occur. CONCLUSIONS: Primary anastomosis in selected patients appears safe after left sided emergency colorectal resection. A defunctioning stoma might mitigate against risk of subsequent complications

The impact of conversion on the risk of major complication following laparoscopic colonic surgery: an international, multicentre prospective audit.

This is the peer reviewed version of the following article: The and E. S. o. C. c. groups (2018). "The impact of conversion on the risk of major complication following laparoscopic colonic surgery: an international, multicentre prospective audit." Colorectal Disease 20(S6): 69-89., which has been published in final form at https://doi.org/10.1111/codi.14371. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.BACKGROUND: Laparoscopy has now been implemented as a standard of care for elective colonic resection around the world. During the adoption period, studies showed that conversion may be detrimental to patients, with poorer outcomes than both laparoscopic completed or planned open surgery. The primary aim of this study was to determine whether laparoscopic conversion was associated with a higher major complication rate than planned open surgery in contemporary, international practice. METHODS: Combined analysis of the European Society of Coloproctology 2017 and 2015 audits. Patients were included if they underwent elective resection of a colonic segment from the caecum to the rectosigmoid junction with primary anastomosis. The primary outcome measure was the 30-day major complication rate, defined as Clavien-Dindo grade III-V. RESULTS: Of 3980 patients, 64% (2561/3980) underwent laparoscopic surgery and a laparoscopic conversion rate of 14% (359/2561). The major complication rate was highest after open surgery (laparoscopic 7.4%, converted 9.7%, open 11.6%, P < 0.001). After case mix adjustment in a multilevel model, only planned open (and not laparoscopic converted) surgery was associated with increased major complications in comparison to laparoscopic surgery (OR 1.64, 1.27-2.11, P < 0.001). CONCLUSIONS: Appropriate laparoscopic conversion should not be considered a treatment failure in modern practice. Conversion does not appear to place patients at increased risk of complications vs planned open surgery, supporting broadening of selection criteria for attempted laparoscopy in elective colonic resection