scholarly journals Are we ready to design oral PROTACs®?

ADMET & DMPK ◽  
2021 ◽  
Author(s):  
Diego Garcia Jimenez ◽  
Matteo Rossi Sebastiano ◽  
Giulia Caron ◽  
Giuseppe Ermondi
Keyword(s):  
Open Access ◽  
Ad Hoc ◽  
Statistical Study ◽  
Chemical Space ◽  
E3 Ligases ◽  
Creative Commons ◽  
Chemical Structures ◽  
Set Up ◽  
Approved Drugs ◽  
Open Access Article

PROTACs® are expected to strongly impact the future of drug discovery. Therefore, in this work we firstly performed a statistical study to highlight the distribution of E3 ligases and POIs collected in PROTAC-DB, the main online database focused on degraders. Moreover, since the emerging technology of protein degradation deals with large and complex chemical structures, the second part of the paper focuses on how to set up a property-based design strategy to obtain oral degraders. For this purpose, we calculated a pool of seven previously ad hoc selected 2D descriptors for the 2258 publicly available degraders in PROTAC-DB (average values: MW= 972.9 Da, nC= 49.5, NAR= 4.5, PHI= 17.3, nHDon= 4.5, nHAcc= 17.7 and TPSA= 240 Å2) and compared them to a dataset of 50 bRo5 orally approved drugs. Then, a chemical space based on nC, PHI and TPSA was built and subregions with optimal permeability and bioavailability were identified. Bioavailable degraders (ARV-110 and ARV-471) tend to be closer to the Ro5 region, using mainly semi-rigid linkers. Permeable degraders, on the other hand, are placed in an average central region of the chemical space but chameleonicity could allow them to be located closer to the two Arvinas compounds. ©2021 by the authors. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/). ©2021 by the authors. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).

scholarly journals PROTACs and Building Blocks: The 2D Chemical Space in Very Early Drug Discovery

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 672
Author(s):  
Giuseppe Ermondi ◽  
Diego Garcia-Jimenez ◽  
Giulia Caron
Keyword(s):  
Ad Hoc ◽  
Chemical Space ◽  
Flexible Structures ◽  
Building Blocks ◽  
Correlation Matrices ◽  
Chemical Structures ◽  
Box Plots ◽  
Physicochemical Descriptors ◽  
Degradation Activity ◽  
Approved Drugs

Targeted protein degradation by PROTACs has emerged as a new modality for the knockdown of a range of proteins, and, more recently, it has become increasingly clear that the PROTAC chemical space requires characterization through a pool of ad hoc physicochemical descriptors. In this study, a new database named PROTAC-DB that provides extensive information about PROTACs and building blocks was used to obtain the 2D chemical structures of about 1600 PROTACs, 60 E3 ligands, 800 linkers, and 202 warheads. For every structure, we calculated a pool of seven 2D descriptors carefully identified as informative for large and flexible structures. For comparison purposes, the same procedure was applied to a dataset of about 50 bRo5 approved drugs reported in the literature. Correlation matrices, PCAs, box plots, and other graphical tools were used to define and understand the chemical space covered by PROTACs and building blocks in relation to other compounds. Results show that linkers have different properties than E3 ligands and warheads. Polar descriptors additivity is not respected when passing from building blocks to degraders. Moreover, a very preliminary analysis based on three PROTACs with high, intermediate, and low permeability showed how the most permeable compounds seem to occupy a region closer to bRo5 drugs and, thus, exhibit different properties than impermeable compounds. Finally, a second database, PROTACpedia, was used to discuss the relevance of physicochemical descriptors on degradation activity.

scholarly journals Promoting Research Culture at Indus Health Network

2019 ◽  
Vol 36 (ICON-Suppl) ◽  
Author(s):  
Shaukat Ali Jawaid
Keyword(s):  
Open Access ◽  
Original Work ◽  
Research Culture ◽  
Health Network ◽  
Creative Commons ◽  
Special Supplement ◽  
Open Access Article

doi: https://doi.org/10.12669/pjms.36.ICON-Suppl.1861 How to cite this:Jawaid SA. Promoting Research Culture at Indus Health Network. Pak J Med Sci. Special Supplement ICON 2020. 2020;36(1):S2. doi: https://doi.org/10.12669/pjms.36.ICON-Suppl.1861 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

scholarly journals A Framework for Protecting Pregnant Women in the Era of COVID-19 Pandemic

2021 ◽  
Vol 10 (1) ◽  
pp. 109-112
Author(s):  
Deepa Dongarwar ◽  
Veronica Ajewole ◽  
Kiydra Harris ◽  
Emmanuella Oduguwa ◽  
Theresa Ofili ◽  
...  
Keyword(s):  
Open Access ◽  
Severe Acute Respiratory Syndrome ◽  
Best Practices ◽  
Global Health ◽  
Pregnant Women ◽  
Original Work ◽  
Creative Commons ◽  
New Challenges ◽  
Work First ◽  
Open Access Article

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent for the coronavirus disease 2019 (COVID-19) pandemic, highlighted and compounded problems while posing new challenges for the pregnant population. Although individual organizations have provided disparate information, guidance, and updates on managing the pregnant population during the current COVID-19 pandemic, it is important to develop a collective model that highlights all the best practices needed to protect the pregnant population during the pandemic. To establish a standard for ensuring safety during the pandemic, we present a framework that describes best practices for the management of the pregnant population during the ongoing COVID-19pandemic.   Copyright © 2021 Dongarwar, et al. Published by Global Health and Education Projects, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in this journal, is properly cited.

scholarly journals Problems faced by Researchers and pressure on Impact Factor Journal Editors

2021 ◽  
Vol 37 (3) ◽  
Author(s):  
Shaukat Ali Jawaid
Keyword(s):  
Open Access ◽  
Impact Factor ◽  
Original Work ◽  
Impact Factor Journal ◽  
Creative Commons ◽  
Journal Editors ◽  
Open Access Article

doi: https://doi.org/10.12669/pjms.37.3.4296 How to cite this:Jawaid SA. Problems faced by Researchers and pressure on Impact Factor Journal Editors. Pak J Med Sci. 2021;37(3):616-620.  doi: https://doi.org/10.12669/pjms.37.3.4296 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

scholarly journals Spontaneous Detorsion of Sigmoid Volvulus in a patient with Nineteen-Volvulus episode history: A rare outcome of an extremely rare clinical entity

2021 ◽  
Vol 37 (7) ◽  
Author(s):  
Sabri Selcuk Atamanalp ◽  
Esra Disci ◽  
Cansu Tatar Atamanalp ◽  
Refik Selim Atamanalp
Keyword(s):  
Open Access ◽  
Original Work ◽  
Sigmoid Volvulus ◽  
Clinical Entity ◽  
Rare Clinical Entity ◽  
Creative Commons ◽  
Multiple Episode ◽  
Open Access Article

Sigmoid volvulus (SV) recurrence more than 10 times is an extremely rare clinical entity and spontaneous detorsion is a rare outcome of SV. In this paper, we report a case with 19 previous SV attacks, in last of which spontaneous detorsion occurred. Such a multiple-episode history as well as an unexpected recovery was unique in a 1,036-case clinical profession of Ataturk University with SV over a 54.5-year period. doi: https://doi.org/10.12669/pjms.37.7.4703 How to cite this:Atamanalp SS, Disci E, Tatar Atamanalp C, Atamanalp RS. Spontaneous Detorsion of Sigmoid Volvulus in a patient with Nineteen-Volvulus episode history: A rare outcome of an extremely rare clinical entity. Pak J Med Sci. 2021;37(7):---------.  doi: https://doi.org/10.12669/pjms.37.7.4703 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

scholarly journals 2019 Health Equity Summer Research Summit Organized by the Center of Excellence in Health Equity, Training and Research, Baylor College of Medicine, Houston, Texas 77030, USA on June 18th, 2019

2020 ◽  
Vol 9 (2s) ◽  
pp. S1-S46
Author(s):  
A Uribe-Gomez ◽  
Abraham A. Salinas-Miranda ◽  
Acara E. Turner ◽  
Adriana M. Strutt ◽  
Adrienne Joseph ◽  
...  
Keyword(s):  
Open Access ◽  
Health Equity ◽  
Original Work ◽  
Baylor College ◽  
Creative Commons ◽  
Center Of Excellence ◽  
Training And Research ◽  
Open Access Article

Copyright © 2020 Harris. This is an open-access article distributed under the terms of the Creative Commons At - tribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

scholarly journals Exploration of constructs of professionalism identified in the ABIM framework as perceived by the faculty fitting the Pakistani context

2020 ◽  
Vol 36 (3) ◽  
Author(s):  
Humaira Fayyaz Khan ◽  
Raheela Yasmeen
Keyword(s):  
Open Access ◽  
Focus Group ◽  
Original Work ◽  
Group Discussion ◽  
Local Context ◽  
Ethnographic Research ◽  
Professional Conduct ◽  
Medical College ◽  
Creative Commons ◽  
Open Access Article

Objective: Domains of professionalism are well-described in the literature. Examining the elements of Professionalism in the local context have received less attention from education experts. The aim of the study was to explore the construct of professionalism as perceived by the faculty that fitted the Pakistani context identified in the ABIM framework of professionalism. Methods: This qualitative ethnographic research was conducted involving nine participants from Islamic International Medical College in Riphah University Islamabad. A four hours Focus Group Discussion was undertaken to explore the views of the faculty. The focus group session was audiotaped, transcribed and technique of triangulation was employed. Shortened meaningful unit (SMU) were identified from the transcribed data and analyzed to make codes for themes for the behaviors. Forty-six meaningful units were categorized and codes were identified. The themes were identified under the domains of the ABIM frameworks for the Pakistani context. Results: The participants listed 2-8 elements for each domain of the framework describing the professional conduct which lead to 140 shortened meaningful units. These were organized into 46 higher order codes. Conclusions: The study concludes that that ABIM framework can be used to build consensus regarding the domains of professionalism. No difference was found cross contextually regarding the domains of ABIM framework of professionalism. doi: https://doi.org/10.12669/pjms.36.3.1573 How to cite this:Khan HF, Yasmeen R. Exploration of constructs of professionalism identified in the ABIM framework as perceived by the faculty fitting the Pakistani context. Pak J Med Sci. 2020;36(3):---------. doi: https://doi.org/10.12669/pjms.36.3.1573 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

scholarly journals Report on open access publishing at the College of Education, Health and Human Development, University of Canterbury, New Zealand

2015 ◽  
Author(s):  
Arindam Basu
Keyword(s):  
New Zealand ◽  
Open Access ◽  
Open Access Publishing ◽  
Audience Participation ◽  
Research Committee ◽  
Creative Commons ◽  
Open Access Journals ◽  
Questions And Answers ◽  
Set Up ◽  
The University

Open access publications are those where following the publication itself, the publishers allow anyone to access the article or publication to read, or download without any restriction. It is believed that publishing in open access journals can increase the visibility of the publication, although uncertainties prevail. In a bid to improve the PBRF ratings, the College research committee in its monthly meeting agreed to organise an Open Access Seminar in the college. The seminar was organised on 4th of June, 2015, Thursday. Four speakers were identified. They were: Peter Lund and Anton Angelo from the University of Canterbury Central Library and Researcn Unit, Peter Binfield from PeerJ, and Viriginia Barbour from Australian Open Access Support Group. The topics of the seminar included a brief introduction to open access publishing and the state of the scenario in NZ and Australia and exploration of the issues around green and gold open access, and future directions as to what can be done to increase participation in open access. The seminar was also designed to be an open to all, and free flowing discussion. This seminar followed a format of webinar and on the spot presentations, questions and answers. A web based page was set up using the openly accessible Adobe Connect "room" where participants could connect even if they were not able to attend in person. Dr Binfield and Barbour were overseas speakers and they connected using the webinar (Adobe Connect). Mr Lund and Angelo were local speakers and they came to the meeting hall directly and spoke. A resource website was set up and the event was recorded for later viewing. The event was publicised across the university and through online channels. About 30 individuals attended the meeting in person, and ten participants joined online. Mr Lund introduced the concept of open access at the University of Canterbury, and introduced the concepts of gold and green open access; Mr Angelo introduced the concepts of creative commons, and Drs Binfield and Barbour discussed models of open access and the situation in Australia. The floor was open for questions, and clarifications and discussions from the audience participation. Key takeaway lessons from the seminar included: at the University of Canterbury, scholars are active in publishing in Open Access channels; green open access is popular in Australia and in New Zealand; newer channels and novel publishing models uitlising the Open Access formats are emerging and becoming popular; while some reservations about quality in open access exist, quality of peer review in OA journals were at par.

scholarly journals Common reasons for not accepting manuscripts for further processing after editor’s triage and initial screening

2018 ◽  
Vol 35 (1) ◽  
Author(s):  
Shaukat Ali Jawaid ◽  
Masood Jawaid
Keyword(s):  
Open Access ◽  
Original Work ◽  
Initial Screening ◽  
Creative Commons ◽  
Open Access Article

How to cite this:Jawaid SA, Jawaid M. Common reasons for not accepting manuscripts for further processing after editor’s triage and initial screening. Pak J Med Sci. 2019;35(1):1-3. doi: https://doi.org/10.12669/pjms.35.1.28 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

scholarly journals Ileosigmoid knotting: An update for Atamanalp classification

2021 ◽  
Vol 37 (3) ◽  
Author(s):  
Sabri Selcuk Atamanalp
Keyword(s):  
Open Access ◽  
Emergency Surgery ◽  
Poor Prognosis ◽  
Original Work ◽  
Double Loop ◽  
Classification Methods ◽  
Single Centre ◽  
Creative Commons ◽  
Comprehensive Method ◽  
Open Access Article

Ileosigmoid knotting (ISK) is an extremely rare double-loop bowel obstruction. ISK is treated by emergency surgery with a relatively poor prognosis. Although some classification methods have been developed for ISK to date, the most comprehensive method was defined in 2018. Then, some subjects concerning this issue were evaluated in the literature. The aim of this paper is to update the last classification method in light of both the evaluations in the literature and our clinical experience with 80 ISK cases, which is one of the largest published single-centre ISK series. doi: https://doi.org/10.12669/pjms.37.3.3179 How to cite this:Atamanalp SS. Ileosigmoid knotting: An update for Atamanalp classification. Pak J Med Sci. 2021;37(3):---------. doi: https://doi.org/10.12669/pjms.37.3.3179 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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