bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physical Instabilities of Therapeutic Monoclonal Antibodies: A Critical
Review
Authors: Mehta Priti , Bana Arpit Arun K. , Ramnani Khushboo Ashok Kumar 
Published: June 2022

Abstract:
The proteinaceous nature of monoclonal antibodies (mAbs) makes them highly sensitive to
various physical and chemical conditions, thus leading to instabilities that are classified as physical
and chemical instabilities. In this review, we are discussing in detail the physical instability of mAbs
because a large number of articles previously published solely focus on the chemical aspect of the instability
with little coverage on the physical side. The physical instabilities of mAbs are classified into
denaturation and aggregation (precipitation, visible and subvisible particles). The mechanism involved
in their formation is discussed in the article, along with the pathways correlating the denaturation of
mAb or the formation of aggregates to immunogenicity. Further equations like Gibbs-Helmholtz involved
in detecting and quantifying denaturation are discussed, along with various factors causing the
denaturation. Moreover, questions related to aggregation like the types of aggregates and the pathway
involved in their formation are answered in this article. Factors influencing the physical stability of the
mAbs by causing denaturation or formation of aggregates involving the structure of the protein, concentration
of mAbs, pH of the protein and the formulations, excipients involved in the formulations,
salts added to the formulations, storage temperature, light and UV radiation exposure and processing
factors are mentioned in this article. Finally, the analytical approaches used for detecting and quantifying
the physical instability of mAbs at all levels of structural conformation like far and near UV, infrared
spectroscopy, capillary electrophoresis, LC-MS, microflow imagining, circular dichroism and peptide
mapping are discussed.
Computational Investigation of the Interaction of Novel Indene Methylene
Analogues with Acetylcholinesterase from Both Dynamic and Thermodynamic
Perspectives
Authors: Gupta Shraddha M. , Jain Neetesh K. , Yadav Rohitash , Erol Meryem , Celik Ismail , Gupta Manish , Behera Ashok 
Published: June 2022

Background:
Torpedo californica acetylcholinesterase (TcAChE) is an important drug development
target for Alzheimer's disease (AD) therapeutics. The current in silico study aims to recognise indene
methylene-derived compounds acting against TcAChE to gain insight into the molecular interactions.

Objective:
The current study focused on identifying novel inhibitors for Torpedo californica acetylcholinesterase
(TcAChE) by virtual screening, molecular docking, drug-likeness, molecular simulation, and
DFT profile for anti-Alzheimer's activity.

Methods:
Molecular docking, ADMET screening, molecular simulation, and DFT were performed for
drug development having anti-Alzheimer's activity related to Torpedo californica acetylcholinesterase
(TcAChE).

Results:
On the AutoDock Vina algorithms, ligands SD-24 [-12.6, -13.1 kcal/mol], SD-30 [-12.5, -12.6
kcal/mol], SD-42 [-11.8, -12.5kcal/mol] showed promising docking and confirmatory redocking scores
compared to Donepezil [-8, -10.9 kcal/mol], followed by ADMET screening. The best three complexes
were subjected to molecular dynamics simulations (MDSs) over 30 ns to understand the TcAChE dynamics
and behavior in a complex with the ligand. MEP and NBO analysis was performed for the
DFT/B3LYP theory and 6-311G [d,p] base set and Gaussian 09 package program. For MDSs, the root
means square (RMSD) parameter remained stable for 30 ns at 0.25 nm. The ligand-AChE complex
formed 2 to 4 satisfactory intermolecular H bonds, which substantiated the stability of the three compounds
in the protein binding cluster as potent binders. The LUMO (owest unoccupied molecular orbital)-
HOMO (highest occupied molecular orbital) energy gap of the SD24, SD30, and SD42 compounds was
4.0943, 4.2489, and 4.2489 eV, respectively, and stability was ordered as SD24>SD30=SD42.

Conclusion:
The outcome of in silico studies suggests that SD24, SD30, and SD42 compounds have
promising drug-likeness, simulation, and DFT profiles for anti-Alzheimer's activity. However, in vitro
and in vivo studies are required to confirm their biological activities.
Incidence, Current Guidelines and Management of Gastrointestinal Bleeding
after Transcatheter Aortic Valve Replacement: A Systematic Review
Authors: Doshi Rajkumar , Adalja Devina , Zala Harshvardhan , Victor Varun , Sheth Aakash , Willyard Charles , Suzuki Emi , Patel Harsh P. , Majmundar Monil , Vallabhajosyula Saraschandra 
Published: June 2022

Background:
There is a significant increase in morbidity and mortality in patients complicated
by major bleeding following transcatheter aortic valve replacement (TAVR). It has become
more challenging to manage such complications when the patient needs to be on anticoagulation
or antiplatelet agent post-procedure to prevent thrombotic/embolic complications.

Methods:
We systematically reviewed all available randomized controlled trials and observational
studies to identify incidence rates of gastrointestinal bleeding post-procedure. After performing a
systematic search, a total of 8731 patients from 15 studies (5 RCTs and 10 non-RCTs) were
included in this review.

Results:
The average rate of gastrointestinal bleeding during follow-up was 3.0% in randomized
controlled trials and 1.9% among observational studies.

Conclusion:
Gastrointestinal bleeding has been noted to be higher in the RCTs as compared to observational
studies. This review expands knowledge of current guidelines and possible management
of patients undergoing TAVR.
Structure-based in silico and in vitro Analysis Reveals Asiatic Acid as Novel
Potential Inhibitor of Mycobacterium tuberculosis Maltosyl
Transferase
Authors: Sharma Rolee , Singh Kratika , Sharma Akanksha , Upadhyay Tarun Kumar , Hayat-ul-Islam Mohammad , Khan M. Kalim A. , Dwivedi Upendra N. 
Published: June 2022

Aims:
The present study aimed to search for novel potent inhibitor(s) against the recently discovered maltosyltransferase (GlgE) target of M.tb.

Background:
GlgE belongs to an α-amylase family and catalyzes the elongation of cytosolic branched α-glucan. Inactivation of M.tb.GlgE results in DNA damage and rapid death of M.tb. due to the accumulation of a toxic altosyl donor, maltose-1-phosphate (M1P), suggesting that GlgE is an intriguing target for inhibitor design.

Method:
1000 natural compounds were compiled from public databases and literature through virtual screening, of which 25 compounds were found to satisfy all drug-likeness properties and ADME/toxicity criteria, followed by molecular docking with GlgE. Compound(s) showing the lowest binding energy was further subjected to molecular dynamics simulation (MDS) and in vitro analysis.

Results:
Molecular docking analysis allowed the selection of 5 compounds showing significant binding affinity to GlgE targets. Amongst these compounds, asiatic acid exhibited the lowest binding energy (-12.61 kcal/mol). The results of 20-ns MDS showed that asiatic acid formed a stable complex with GlgE. Additionally,asiatic acid exhibited in vitro anti-mycobacterial activity against M.tb. H37Ra, M. bovisBCG, and M. smegmatisstrains.

Conclusion:
The study reveals Asiatic acid as a promising anti-mycobacterial agent that might emerge as a novel natural anti-TB lead in the future.
Effect of Nano-Curcumin on Radiotherapy-Induced Skin Reaction in
Breast Cancer Patients: A Randomized, Triple-Blind, Placebo-Controlled
Trial
Authors: Farhood Bagher , Najafi Masoud , Talakesh Tamara , Tabatabaee Nasibeh , Atoof Fatemeh , Aliasgharzadeh Akbar , Sarvizade Mostafa 
Published: June 2022

Purpose:
Despite advances in medical technology, radiation-induced dermatitis occurs in 95% of cancer patients receiving radiation therapy. Currently, there is no standard and effective treat-ment for the prevention or control of radiation dermatitis. The aim of this study was to determine the efficacy of nano-curcumin in alleviating the radiation-induced skin reactions (RISRs) in breast cancer patients.

Methods:
A randomized, triple-blinded, placebo-controlled clinical trial was performed on 42 patients with breast cancer. The patients were randomly allocated to receive radiotherapy plus placebo (control group) and radiotherapy plus 80 mg/day nano-curcumin capsules (treatment group) up to two weeks after the end of treatment. Then, the RISRs (graded by the radiation therapy oncology group (RTOG) scale) and pain level of the patients were evaluated at baseline and weekly. Finally, the results were analyzed by T-test and Pearson chi-square test.

Results:
According to the RTOG scale, 0%, 14.28%, and 85.71% of patients in the control group showed grades 0, 1, and 2 RISRs, respectively. In the treatment group, it was observed that 9.52%, 47.61%, and 42.85% of patients had grades 0, 1, and 2 RISRs, respectively. Compared to the control group, it was found that concomitant use of the nano-curcumin supplement did not significantly reduce the RISR severity during the first to sixth weeks (P > 0.05); however, there was a significant difference at week 7 (P = 0.01). Moreover, the patient-reported pain, as the secondary endpoint, was significantly reduced in the treatment group compared with the control group (P < 0.05).

Conclusions:
In general, it was found that the administration of nano-curcumin could alleviate radia-tion-induced skin toxicity of breast cancer patients, but this effect was not significant.

Trial Registration Number:
Registered in the Iranian Registration of clinical trials (IRCT2020051304-7427N1).
La ilusión del mérito. Capital cultural y reproducción
Authors: Grau-Grau Marc 
Published: June 2022

Celebrando el 50 aniversario de la publicación de La Reproducción (Bourdieu and Passeron, 1970), y ante el auge del proyecto meritocrático en muchas esferas de nuevas vidas, el objetivo del presente estudio es comprender la percepción del esfuerzo, y el talento, en la obtención de la posición de trabajo actual, ayudando a desvelar como la incorporación de distintos capitales a lo largo de la vida (estructuras de primer orden) construye la percepción del propio mérito como elemento explicativo del logro del último empleo. Para ello el estudio examina las respuestas de 2482 entrevistas a españoles de más de 18 años de 255 municipios en 50 provincias (Estudio CIS nº 3176. Desigualdad y movilidad social), usando el análisis de correspondencia múltiple, no sólo para recuperar una técnica estadística muy apreciada por Bourdieu sino también por su naturaleza relacional.
COMPRESSIVE CYLINDER STRENGTH AND DEFORMABILITY OF EXPANDED CLAY FIBER-REINFORCED CONCRETE WITH POLYPROPYLENE FIBER
Authors: Maskalkova Yuliya , Rzhevutskaya Valeryia 
Published: June 2022

This article presents the experimental studies results of the reinforcement effect with polypropylene fiber (0.5 %, 1 %, and 1.5 %) on the strength (compressive cylinder strength) and deformation (compressive strain) characteristics for expanded clay concrete. The most effective fiber percentage is the content of 1.5 % by weight of the cement mass, based on obtained experimental results. An increase in the compressive cylinder strength (up to 13 %), a significant increase in the value of ultimate compressive strain in concrete (corresponding to the peak stress) of the stress-strain diagram (up to 50 %), and the plastic failure of expanded clay fiber-reinforced concrete is noted.
KEBIJAKAN UNI EROPA RED II DAN DELEGATED ACT TERHADAP PERDAGANGAN PRODUK KELAPA SAWIT INDONESIA
Authors: Sinaga Valerie Selvie , Foekh Refindie Micatie Esani 
Published: June 2022

ABSTRAK
Indonesia merupakan salah satu negara produsen sekaligus pengekspor minyak kelapa sawit terbesar di dunia. Pada tahun 2018 Uni Eropa memberlakukan Renewable Energy Directive (RED II) 2018/2001 dengan maksud untuk mengurangi emisi gas rumah kaca dan deforestasi sekaligus meningkatkan penggunaan energi terbarukan. Kebijakan RED II dan Delegated Act telah menempatkan secara implisit kelapa sawit sebagai penyebab dari emisi gas rumah kaca dan deforestasi. RED II dan Delegated Act mengkategorikan kelapa sawit sebagai High Indirect Land Use Change Risk. ILUC terjadi apabila lahan yang dahulunya merupakan lahan pertanian dialihfungsikan untuk memproduksi biofuel, ini sering terjadi pada lahan stok karbon yang tinggi seperti hutan, lahan basah dan lahan gambut, sedangkan kelapa sawit hanya tumbuh di lahan gambut. Indonesia selaku penghasil kelapa sawit mengajukan protes dengan mengajukan gugatan inisiasi awal ke WTO tanggal 9 Desember 2019. Dalam artikel ini akan dibahas permasalahan apakah RED II dan Delegated Act oleh Uni Eropa telah melanggar prinsip Most Favoured Nations (MFN)? Metode penelitian yang digunakan adalah yuridis normatif, dengan kesimpulan bahwa kebijakan RED II dan Delegated Act harus dibatalkan karena melanggar prinsip MFN sebagai prinsip utama dalam perdagangan internasional.
Kata kunci: delegated act; hukum perdagangan internasional; prinsip mfn.

ABSTRACT
Indonesia is one of the largest producers and exporters of palm oil in the world. In 2018 the European Union enacted the revision of the Renewable Energy Directive (RED II) 2018/2001 to reduce greenhouse gas emissions and deforestation while increasing the use of renewable energy. RED II and Delegated Act policies have implicitly placed oil palm as a cause of greenhouse gas emissions and deforestation. RED II and Delegated Act categorize palm oil as High Indirect Land Use Change Risk (ILUC). ILUC occurs when land that was once agricultural land is converted to produce biofuel. This often occurs on high carbon stock lands such as forests, wetlands, and peatlands. Whereas only oil palm grows on peatlands. Indonesia did not accept the RED II Policy and Delegated Act by filing a lawsuit with initial initiation to the WTO on 9 December 2019. This article tried to seek whether RED II and Delegated Act policies violate the Most Favored Nations (MFN) principle. The research method used is normative juridical. It is concluded that RED II and Delegated Act policies must be revoked because they violate the principle of MFN as a main principle in international trade.
Keywords: delegated act; international trade law; mfn principle.
KEBIJAKAN PENEGAKAN HUKUM LINGKUNGAN ATAS PELANGGARAN ADMINISTRASI TATA RUANG DAN ALIH FUNGSI LAHAN SEMPADAN SUNGAI DALAM RANGKA TERWUJUDNYA TATA RUANG YANG BERKELANJUTAN
Authors: Siregar Wildan , Nurlinda Ida , Priyanta Maret 
Published: June 2022

ABSTRAKPenataan ruang merupakan salah satu instrument pengendalian dan pengeleloaan lingkungan hidup, pemanfaatan ruang harus sesuai dengan peruntukannya dengan mempertimbangkan keberlanjutan lingkungan sesuai dengan fungsinya, pemanfaatan ruang yang berkualitas yakni mewujudkan perlindungan fungsi ruang dan mencegah serta menanggulangi dampak negatif terhadap lingkungan, dan mewujudkan keseimbangan antara kepentingan ekologi, sosial dan ekonomi. Tata ruang sering di abaikan dalam pemanfaatannya, misalnya pelangaran atas sempadan sungai, Sempadan sungai berfungsi sebagai ruang penyangga antara ekosistem sungai dan daratan, agar fungsi sungai dan kegiatan manusia tidak saling terganggu. namun pada kenyataannya sempadan sungai beralih fungsi yang berdampak buruk bagi lingkungan. Penataan ruang memiliki peranan penting untuk menjaga fungsi fungsi ruang yang berkelanjutan, segala pemanfaatan ruang harus berdasarkan kajian RTRW yang sudah di rumuskan ke dalam peraturan tata ruang baik di level Nasional dan daerah, yang saling bersinergi satu sama lain. Untuk di level daerah peran dari pemerintah daerah sangatlah penting dalam pengambilan keputusan pemanfaatan ruang, perlu upaya yang serius dan konsisten untuk selalu bersandar kepada peraturan tata ruang. Sehingga pemanfaatan sesuai dengan fungsinya dapat terwujud dan kerusakan lingkungan dapat di Kelola dengan baik. Kata kunci: penegakan hukum lingkungan; tata ruang; pembangunan berkelanjutan; sempadan sungai
ABSTRACTSpatial planning is one of the environmental control and management instruments, the use of space must be in accordance with its designation by considering environmental sustainability in accordance with its function, quality use of space, namely realizing the protection of space functions and preventing and overcoming negative impacts on the environment, and realizing a balance between ecological interests. , social and economic. Spatial planning is often neglected in its utilization, for example the violation of river boundaries. River borders function as a buffer space between river ecosystems and land, so that river functions and human activities are not disturbed by each other. but in reality the river border has changed its function which has a negative impact on the environment. Spatial planning has an important role to maintain sustainable spatial functions, all spatial uses must be based on the RTRW study that has been formulated into spatial regulations both at the national and regional levels, which synergize with each other. At the regional level, the role of local governments is very important in making decisions on spatial use, serious and consistent efforts are needed to always rely on spatial regulations. So that utilization according to its function can be realized and environmental damage can be managed properly.Keywords: environmental law enforcement; spatial planning; sustainable development; river border
MENINJAU ULANG GAGASAN GREEN CONSTITUTION: MENGUNGKAP MISKONSEPSI DAN KRITIK
Authors: Nur Fauzan Muhammad Pasha 
Published: June 2022

ABSTRAK
Belakangan, green constitution menjadi kajian hukum yang menarik ketika menyoal perlindungan lingkungan di Indonesia. Beberapa ahli menyoroti prospeknya dalam menyelesaikan permasalahan lingkungan di Indonesia. Namun, terlepas dari prospeknya tersebut, apakah green constitution sebagai gagasan intelektual merupakan gagasan yang valid, terjustifikasi, dan memiliki dasar fakta serta logika yang kuat? Tulisan ini diarahkan untuk menjawab pertanyaan tersebut. Dalam upaya menjawab pertanyaan tersebut, penulis berusaha menguraikan green constitution beserta fondasi filosofisnya dengan membedahnya ke dalam dua titik penekanan, yakni penekanan ontologis dan penekanan etis. Artikel ini mendapati bahwa gagasan green constitution berbicara lebih dari sekedar konstitusionalisasi norma hukum lingkungan, sebab green constitution merupakan kritik terhadap struktur politik yang bersifat antroposentris, sehingga menjadi pangkal dari berbagai masalah lingkungan. Artikel ini juga berkesimpulan bahwa green constitution memiliki beberapa kegagalan dalam segi ontologis dan etis sehingga, gagasan green constitution merupakan gagasan dengan dasar logika dan fakta yang lemah.
Kata kunci: Antroposentrisme; Ekosentrisme; Green Constitution; Konstitusi; Lingkungan

ABSTRACT
Green constitution has become an interesting topic in legal studies concerning environmental protection in Indonesia. Some jurists highlight it’s prospect to solve the environmental crisis in Indonesia. However, regardless of its prospective offer, it is still necessary to question whether green constitution as an intellectual idea was valid, justified, with strong logical and factual foundation; this article is aimed to answer that question. This article elaborates the key concept of green constitution and its philosophical foundation by dissecting the concept into two points: ontological and ethical. This article finds that the concept of green constitution is more than just the constitutionalization of environmental law norms. Green constitution is a critique of anthropocentric political structures as a root of various environmental problems. This article then concluded that the concept of green constitution has some failures in both ontological and ethical points; therefore, the concept has no solid logical and factual foundation.
Keywords: Anthropocentrism; Constitution; Ecocentrism; Environment; Green Constitution
DEKONSTRUKSI PEMBANGUNAN BERKELANJUTAN MELALUI OTONOMI DAERAH DALAM PENGELOLAAN SUMBER DAYA AIR PASCA OMNIBUS LAW
Authors: Kusumaputra Ardhiwinda 
Published: June 2022

ABSTRAK
Dinamika hukum pengelolaan sumber daya air di Indonesia, telah mengarahkan pada suatu bentuk inkonsistensi pengaturannya. Terjadinya tarik ulur hak otonomi, antara pemerintah pusat dan pemerintah daerah, terlihat sejak adanya Undang-Undang Nomor 11 Tahun 2020 tentang Cipta Kerja (Omnibus Law). Terdapat dua masalah utama, pertama, mengapa terjadi reduksi hak otonomi Pemerintah Daerah dalam hal melakukan pengelolaan atas sumber daya air pasca berlakunya UU No. 11 Tahun 2020? Kedua, bagaimana upaya yang dilakukan untuk tetap mengoptimalkan hak otonomi pemerintah daerah dalam melakukan pengelolaan sumber daya air pasca berlakunya UU No. 11 Tahun 2020? Penelitian ini merupakan penelitian yuridis normatif. Dilakukan pendekatan perundang-undangan, dan hermeneutika. Pasal 33 ayat (3) UUD NRI 1945, menjadi dasar konstitusional bagi Pemerintah Pusat untuk memperkuat kewenangannya atas sumber daya air. Pemerintah daerah lebih diarahkan sebagai pelaksana dari pemerintah pusat. Apalagi, UU No. 11 Tahun 2020 dimaksudkan untuk percepatan pertumbuhan investasi oleh Pemerintah Pusat. Oleh karena itu, dekonstruksi atas prinsip pembangunan berkelanjutan ini dilakukan dengan mengarahkan pada prosperity bagi masyarakat ditingkat daerah dari adanya sumber daya air. Memaksimalkan peran pengawasan dari pemerintah daerah.
Kata kunci: Dekonstruksi; Pembangunan Berkelanjutan; Otonomi Daerah; Sumber Daya Air

ABSTRACT
Regulation of water resources management in Indonesia, has led to inconsistency in its regulation. The tug-of-war between the central government and local governments has taken place since Law Act Number 11 of 2020 concerning Job Creation (Omnibus Law) was introduced. First, why there are a reduction in the autonomy rights of the Regional Government in terms of managing water resources after the enactment of Act No. 11 Year 2020? Second, how are the efforts made to continue to optimize the autonomy rights of local governments in managing water resources after the enactment of Act no. 11 Year 2020? This research is a normativejuridical research. A statutory and hermeneutical approach is carried out. Article 33 paragraph (3) of the 1945 Constitution of the Republic of Indonesia becomes the constitutional basis for the Central Government to strengthen its authority over water resources. Local governments are more directed as implementers of the central government. Moreover, Act no. 11 of 2020 is intended to accelerate investment growth by the Central Government. Therefore, the deconstruction of the principle of sustainable development is carried out by directing the prosperity for the community at the regional level from the presence of water resources. Maximizing the supervisory role of the Regional Government.
Keywords: Deconstruction; Sustainable Development; Regional autonomy; Water resources