bluuebunny/crossref_metadata_2025 huggingface dataset:
Headaches associated with COVID-19
Authors: Tabeeva G. R.
Published: April 2023

Headache is a common symptom of both the acute and post-COVID-19 periods which often persists for a long time. Headache is the leading symptom among all the neurological manifestations of COVID-19, and it also can be a severe deconditioning disorder in about one fifth of patients. A new type of headache may occur or an existing primary cephalal gia pattern may worsen in a patient with COVID-19. During the acute period of infection, cephalgia in most patients can be considered as a headache associated with acute viral infections. However, other forms such as a cough headache, exertional headache, etc. are often considered. In these cases, cephalgic manifestations correlate with other COVID-19 symptoms. The long-term persistent headaches, as one of the most frequent and persistent symptoms of the post-COVID syndrome, often occur according to the type of tension headaches and migraines and are significantly more often detect ed in people with a prior history of cephalalgia. The diversity of headache phenotypes in COVID-19 requires the involve ment of universal strategies for their management. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely investigated and commonly used to relieve pain in clinical practice, as well as fever and other symptoms of infection. The long-term experience with the use of NSAIDs in clinical practice, the availability of clinical data and the results of special studies reveal the possibility of their usage in patients with COVID-19 and complaints of headaches. However, a thorough analysis of current records of their use in patients with COVID-19 is required for the effective and safe use of NSAIDs in this category of patients.
Experience with non-immunogenic staphylokinase for intravenous thrombolysis in ischemic stroke: analysis of hospital registry data
Authors: Kulesh A. A. , Syromyatnikova L. I. , Krapivin S.
Published: April 2023

Introduction. Intravenous thrombolysis (IT) is the primary method of reperfusion therapy for ischemic stroke. Over the past couple of years, there has been a global trend towards the predominant use of the bolus forms of thrombolytic drugs that is caused by necessity to increase the reperfusion therapy rate to achieve its best outcomes.

Aim. To evaluate the efficacy and safety of the use of non-immunogenic staphylokinase for IT in ischemic stroke in real-world clinical practice of the regional vascular center.

Materials and methods. The clinical outcomes of the cohort of 50 patients who underwent IT with non-immunogenic staphylokinase were analysed.

Results. The age of the patients ranged from 46 to 94 years and averaged 71.8 ± 10.0 years; 22% of patients were over 80 years of age. The NIHSS score at admission varied from 3 to 23 scores and averaged 11 (8-14) scores. 36% of patients had large artery occlusions. 14% of patients received a step-wise reperfusion therapy. The median door-to-needle time was 23 (18-26) minutes. 52% of patients didn’t develop any infarction area during control neuroimaging. 62% of patients required no further rehabilitation. Hospital mortality was 12%. 18% of patients developed hemorrhagic conversion mainly in the form of hemorrhagic infarction. 1 patient had a symptomatic hemorrhagic conversion. Major bleeding and angioedema were not observed.

Conclusion. The analysis of 50 consecutive cases of IT in ischemic stroke using non-immunogenic staphylokinase indicates the high efficiency and safety of this method of reperfusion therapy.
Difficulties in the treatment of primary osteoarthritis
Authors: Bashkova I. B. , Busalaeva E. I.
Published: April 2023

Management of patients with primary osteoarthritis (OA) is often a difficult task due to the specifics of the course of the disease, comorbidity, and low compliance of patients to treatment methods, including symptomatic slow acting drugs (SYSADOA). More than half of the surveyed practitioners (62.2%) express doubts about patients’ adherence to SYSADOA treatment. The described clinical observation demonstrates difficulties in the treatment of primary OA in a patient with comorbidity and low compliance. A three-year course therapy of orally administered SYSADOA did not have a significant effect, and new joints were involved in the process. Thus, the patient was offered a shorter course of therapy (10 injections) with a drug from the SYSADOA group. Its active component is a bioactive extractextract from a small sea fish (Ambene® Bio), created using a unique patented technology. There have been studies of the drug and its clinical efficacy described in literature. In the described case, a short course of therapy contributed to an increase in compliance to treatment. A repeated course of 10 injections every other day was carried out after 6 months. At the same time, the patient refused to take non-steroidal anti-inflammatory drugs. Subjective improvement was confirmed by laboratory and instrumental methods.
Muğla-Yatağan İlçesi Eskihisar’da Türk Dönemi Eserleri
Authors: KUNDURACI Osman , BAHARGÜLÜ Nurcan , YİĞİTER Elif
Published: April 2023

Bu makalede Muğla İli Yağan İlçesi Eskihisar’da yer alan Türk dönemine ait eserler ele alınmıştır. Günümüze kadar sürekli yerleşim gören Eskihisar, Stratonikeia Antik Kentiyle iç içe geçmiş, Beylikler döneminden Cumhuriyet dönemine kadar devamlılık gösteren eserleri izleyebildiğimiz önemli bir yerleşmedir. Özellikle Bizans döneminden sonra Türkler tarafından iskân edilmeye başlanan Eskihisar’da Selçuklu hamam geleneğinde yapılmış küçük ölçekli bir köy hamamı bulunmaktadır. Plan ve yapım teknikleri bakımından 14-15 yy. yapısı olduğu görülmektedir. M. 1876 tarihinde Şaban Ağa tarafından yaptırılan kare bir harime sahip ve revaklı bir son cemaat yeri olan cami geç dönem Osmanlı yapılarından birisidir. Bu caminin etrafında oluşturulan köy meydanında da mesleklerin icra edildiği ticaret yapıları yer almaktadır. Bu çalışmada daha çok geç dönem Osmanlı ve Erken Cumhuriyet dönemine ait sivil mimarlık örnekleri ele alınmıştır. Geleneksel Muğla evleri özelliklerine sahip bu yapılar genellikle iki katlı, kırma çatılı ve bir avlu içerisinde yer alan oldukça sade yapılardır. Makaleye dâhil ettiğimiz bu eserler hamam, cami, ticaret yapıları ve çok sayıda sivil mimarlık örneği çalışmamızın esasını oluşturmaktadır. İncelenen eserler; mimarlık ve sanat tarihi açısından ele alınarak bütün özellikleriyle kentin Antik dönemden günümüze gelişen kent dokusu ortaya konmaya çalışılmıştır.
Dilbilgisel Kanıtsallık İşaretleyicilerinin Sözlükselleşmesi: Özbek Türkçesinde mish-mish(lar)
Authors: ÜZÜM Melike
Published: April 2023

Türk lehçeleri, önermeye temel oluşturan bilginin kaynağını dilbilgisel olarak işaretleyen dillerden biri olması nedeniyle kanıtsallık incelemelerinde önemli bir yere sahiptir. Bu çerçevede Eski Türkçeden itibaren görülen -mIş görünüş-zaman ve kanıtsallık, er-miş ise kanıtsallık işaretleyicisi olarak ele alınır. Çoğu lehçede dilbilgiselleşen e(r)mish, Özbek Türkçesinde aktarımsallık için kullanılmakla birlikte kanıtsallığın aktarımsallık ulamının anlam alanında yineleme yoluyla mish-mish(lar) şeklinde sözlükselleşmiştir. Sözlükselleşen biçimbirim, sözlükte madde başı olarak ‘rivayet, söylenti’ eş anlamlı sözcükleriyle tanımlanır. Dilbilgisel kanıtsallık işaretleyicisinden gelişen sözlük birimin benzer kullanımlarına Kıbrıs ağzında, Kırgız ve Kazak Türkçesi gibi diğer Türk lehçelerinde de rastlanır. Dört farklı Türk lehçesinde doğruladığımız gelişimler ve hepsinin kanıtsallığın anlam alanında sözlükselleşmesi, dilbilgisel aktarımsallık işaretleyicilerinin sözlükselleşme eğilimi olduğunu göstermektedir. Bu çalışmada, dilbilgisel kanıtsallık işaretleyicisinin aktarımsallık ulamının anlam alanında sözlükselleşmesi, Özbek Türkçesinde kanıtsallık ulamı çerçevesinde ele alınmıştır. Çalışmanın amacı Türk lehçelerinde sözlükselleşen yapılar hakkında veri sunmak, kanıtsallık ulamının iletişimdeki önemi ve anlam alanının bu gelişimdeki rolünü açıklamaktır. İncelemede nitel ve nicel araştırma yöntemleri kullanılmıştır. İnceleme sonucunda, mish-mish(lar) sözlük biriminin yineleme yoluyla bağımlı biçim birimden bağımsız biçim birime geliştiği ortaya konmuştur.
Accuracy evaluation of scour depth equations under the submerged vertical jet
Authors: Guguloth Sai , Pandey Manish
Published: April 2023

Scouring of sediment materials under submerged vertical jets is shown at grade-control structures, downstream of weirs, and submerged vertical water jets have several uses, including seabed sediment removal and dredging in ocean engineering. Numerous studies have been conducted to demonstrate the scour process and the variation of scour profile utilizing various influencing parameters. Many researchers developed equations for predicting the scour hole characteristics. Previous studies identified two types of scour hole depth configurations: static and dynamic scour depth and the variation of scour hole variations differs for long- and short-impinging jet height conditions. In this study, extensive data on non-dimensional static and dynamic scour depth under short- and long-impinging jets acquired from prior literature, and the previously proposed equations of static and dynamic scour depth were analyzed using graphical and statistical analysis. The findings demonstrated that the relationships proposed by Aderibigbe and Rajaratnam (1996) for long-impinging jets and Amin et al. (2021) for short-impinging jets predict the static scour depth better than the other equations. The proposed equations for dynamic scour depth under long- and short-impinging jets are highly biased and inaccurate.
Spatio-temporal changes in urban water consumption during 2 years of the COVID-19 pandemic in southern Brazil
Authors: Tavares Lígia Conceição , Bravo Juan M. , Lehdermann Luisa , Jesus Ronan T. , Almeida Ian R.
Published: April 2023

This study investigated the changes that occurred during the COVID-19 pandemic in urban water consumption in residential, commercial, industrial, and public agencies in the city of São Leopoldo, southern Brazil, which has about 55,000 consumers and over 200,000 inhabitants. Overall, the city increased water consumption by 5.6% during the 2-year pandemic, with 5.9% in 2020 and 5.5% in 2021. Residential and industrial consumption increased by 6.77 and 9.92% in the first year, and by 5.47 and 14.45% in the second year, respectively. On the other hand, commercial and public sector consumption decreased by 5.48 and 46.26% in the first year and 1.83 and 40.99% in the second year, respectively. In the first months of the pandemic, there was a sharp increase in residential water consumption at the same time as a reduction in consumption in the other categories. In contrast, there was a slight return to previous water consumption patterns in the following months. Overall, we can affirm that the more central neighborhoods presented higher changes in water consumption than the peripheral neighborhoods. In addition, the water consumption during the pandemic and pre-pandemic periods was statistically different for residential, industrial, and public consumers.
Modern Collective Transport. The Impact of Public Policy on the Implementation of the EU Legislative Objectives on the Example of Poland
Authors: Jarecki Stefan Akira
Published: April 2023

Urban policy is driven by current trends and ideas. In the 20th century, it was mainly based on modernist views and the most important element of the transport planning policy at that time was the use of the private motor vehicle (car). As a result, transport policies in the 20th century were focused on large-scale road projects, while public transport was marginalized. However, this approach changed drastically at the turn of the 20th and the 21st centuries. Nowadays, the main emphasis is put on environmentally and user-friendly public transport. However, public urban transport often fails to meet the needs of the society. What are the reasons why urban public transport is still not as effective as it should be? The author of this article points in this respect to the poor policy of public bodies responsible for the provision of transport services for the society rather than to the poor quality of the transport law. There are two main areas for improvement - public service planning (defining the service) and cost-effectiveness of providing transport services. The author of the article proposes specific solutions in this regard.
Recent Progress in Selective COX-2 Inhibitor Formulations and Therapeutic
Applications - A Patent Review (2012-2022)
Authors: Mittal Roopal , Sharma Shailesh , Mittal Anu , Mittal Amit
Published: April 2023

Introduction:

Cyclooxygenase (COX), in literature, known as prostaglandin-endoperoxide
synthase (PTGS), is an enzyme that is responsible for the formation of prostanoids, including thromboxane
and prostaglandins from arachidonic acid. COX-1 does housekeeping activity, whereas COX-
2 induces inflammation. Continuous rise in COX-2 gives birth to chronic pain-associated disorders,
i.e., arthritis, cardiovascular complications, macular degeneration, cancer, and neurodegenerative disorders.
Despite their potent anti-inflammatory effects, the detrimental effects of COX-2 inhibitors coexist
in healthy tissues. Non-preferential NSAIDs cause gastrointestinal discomfort, whereas selective
COX-2 inhibitors exert higher cardiovascular risk and renal impairment on chronic use.

Methods:

This review paper covers key patents published between 2012-2022 on NSAIDs and coxibs,
highlighting their importance, mechanism of action, and patents related to formulation and drug combination.
So far, several drug combinations with NSAIDS have been used in clinical trials to treat
chronic pain besides combating the side effects.

Conclusion:

Emphasis has been given on the formulation, drug combination, administration routesmodification,
and alternative routes, i.e., parenteral, topical, and ocular DEPOT, improving its riskbenefit
ratio of NSAIDs to improvise their therapeutic availability and minimize the adverse effects.
Considering the wide area of research on COX-2 and ongoing studies, and future scope of view for
the better use of the NSAIDs in treating debilitating disease-associated algesia.
Therapeutic Potential of Clostridium novyi-NT in Cancer: Current
Knowledge and Future Perspectives
Authors: Sharafabad Behrouz Ebadi , Abdoli Asghar , Abdolmohammadi Khiav Lida , Meskini Maryam , Jamur Parisa , Dilmaghani Azita
Published: April 2023

Resistance to conventional antitumour therapies and Hypoxia in patients with advanced
solid tumours are two major reasons for the failure of conventional anti-tumour therapies. Therefore,
it is important to find a new therapeutic method that can overcome these problems. An attenuated anaerobic
bacterium, Clostridium novyi-NT, could target Hypoxic and Necrotic areas of tumours causing
tumour lysis and stimulating a host anti-tumour immune response. To the best of our knowledge,
the combination of bacterial anti-tumour therapy, chemotherapy, radiotherapy and immunotherapy
may promote tumour regression, inhibit metastasis and develop a new strategy for the treatment of
solid tumours. However, the possible molecular mechanisms of the combined therapies are still the
biggest challenge. This review provides an overview of the history of bacterial cancer therapy and the
development of a non-lethal strain of Clostridium novyi. Below is a precise definition of Hypoxic
conditions in solid tumour tissue. To understand the anticancer effect of Clostridium novyi-NT spores,
possible cell death mechanisms were summarised by the enzyme phospholipase C (nt01cx0979),
which is secreted by Clostridium novyi-NT spores after germination in tumour tissue. The function of
Clostridium novyi-NT spores in stimulating the host immune system to elicit anti-tumour responses
was reviewed. Then, the results of anti-tumour combination therapies based on Clostridium novyi-NT
spores were compiled. Identifying the molecular mechanisms of Clostridium novyi-NT in treating tumours
and inducing cell death in invasive cancer cells, ultimately leading to tumour regression, may
develop promising clinical strategies in the combined treatment of solid tumours.
Identification of Necroptosis-related Subtypes and Characterization of
Tumor Microenvironment Infiltration in Non-small Cell Lung Cancer
Authors: Deng Yan , Lin Yan , Zhou Bin , Jing Qian , Zhang Wei
Published: April 2023

Background:

Necroptosis is correlated with the development, prognosis, and treatment of
tumors. However, the function of necroptosis-associated genes (NRGs) in the tumor microenvironment
(TME) of non-small cell lung cancer (NSCLC) remains unclear.

Methods:

In this study, 1210 NSCLC samples were classified into different subtypes based on the expression
of 66 NRGs by unsupervised clustering analysis, and further analyzed the TME characteristics
of these subtypes. In addition, we identified common differentially expressed genes (co-DEGs) in
NRG subtypes and constructed the NRG score using principal component analysis (PCA) to assess
the NRG-mediated TME characteristics of patients with NSCLC.

Results:

Using unsupervised cluster analysis, 1210 NSCLC samples were divided into NRGcluster A
and B subtypes. The NRGcluster B survived significantly better than the NRGcluster A. TME characterization
revealed that NRGcluster B was upregulated in immune and stromal signaling activation,
whereas NRGcluster A was upregulated in oncogenic signaling. The NRG score constructed based on
co-DEGs of the two NRG-related subtypes was positively correlated with immune cell infiltration and
negatively correlated with the number of cancer stem cells (CSCs) and tumor mutational burden
(TMB). In addition, survival was significantly worse in the low-NRG-score group compared to the
high-NRG-score group. Finally, the assessment of immunotherapeutic efficacy showed that immunotherapeutic
response was significantly worse in the low-NRG-score group compared to the high-
NRG-score group.

Conclusion:

This research reveals that NRGs are associated with the complexity and diversity of
TME in NSCLC. Adopting the NRG score to quantitatively assess NRG-mediated TME in individual
patients with NSCLC may help in planning clinical treatment strategies.
Current Medicinal Insights on Synthetic Small Molecules and Natural
Origin Products as PD-1/PD-L1 Inhibitors
Authors: Pandey Shivanshu , Kurmi Balak Das , Patel Preeti
Published: April 2023

Cancer is one of the leading causes of death worldwide. Each year, millions of people are diagnosed with cancer; hence, researchers have always been curious and busy developing cancer treatments. Despite thousands of studies, cancer is still a major threat to human beings. One of the mechanisms through which cancer invades a human being is the immune escape mechanism, which has been the focus of studies in the past years. PD-1/PD-L1 pathway plays a major role in this im-mune escape. Therefore, research focusing on blocking this pathway has led to the discovery of molecules based on monoclonal antibodies that work quite well, but despite the successful applica-tion of monoclonal antibodies as inhibitors of the PD-1/PD-L1 pathway, there are some drawbacks, such as poor bioavailability and several immune-related adverse effects, which have led the re-searchers toward further investigation, thereby resulting in the discovery of different types of mole-cules, such as small molecule inhibitors, PROTAC-based molecules, and naturally derived peptide molecules that function as inhibitors of the PD-1/PD-L1 pathway. Here, in this review, we have summarized recent findings of these molecules and focused on their structural activity relationship. The development of these molecules has opened more prospects in cancer therapy.
Review on In-vitro Techniques and In-vivo Animals Models for Screening
Diabetes and Diabetic Complications
Authors: Shivam  , Kumar Sushil , Gupta Asheesh Kumar
Published: April 2023

Diabetes mellitus is a type of metabolic disorders. Various pharmaceutical interventions
and animal models have been used to investigate the genetic, environmental, and etiological aspects
of diabetes and its effects. In recent years for the development of ant-diabetic remedies, numerous
novel genetically modified animals, pharmaceutical substances, medical techniques, viruses,
and hormones have been developed to screen diabetic complications. A unique disease-treating
drug with new properties is still being sought after. The current review tried to include all published
models and cutting-edge techniques. Experimental induction of diabetes mellitus in animal
models and in vitro methods are essential for advancing our knowledge, a thorough grasp of pathophysiology,
and the creation of novel therapeutics. Animal models and in vitro techniques are necessary
to develop innovative diabetic medications. New approaches and additional animal models
are required for diabetes research to advance. This is particularly true for models produced via dietary
modifications, which have various macronutrient compositions. In this article, we review the
rodent models of diet-induced diabetic peripheral neuropathy, diabetic retinopathy, and diabetic
nephropathy and critically compare the key characteristics of these micro-vascular complications
in humans and the diagnostic criteria with the parameters used in preclinical research using rodent
models, taking into consideration the potential need for factors that can accelerate or aggravate these
conditions.
Three Different Faces of Schwannoma in Pediatric Patients
Authors: Yazol Merve , Derinkuyu Betul Emine , Boyunaga Oznur
Published: April 2023

Background:

Schwannomas arise from nerve sheaths of cranial, peripheral, and spinal nerve or nerve roots. Most intracranial schwannomas arise from the
cranial nerves, predominantly the vestibulocochlear nerve. In addition to cranial nerve schwannomas, intraparenchymal schwannomas of the brain
and intramedullary schwannomas of the spinal cord are extremely rare.

Case Report:

In our case we describe the imaging findings of three diverse cases of schwannoma at different locations and unique presentations with acute
neurological symptoms in the pediatric age group.

Conclusion:

Schwannomas should be included in the differential diagnosis of intracranial or intraspinal intramedullary space-occupying lesions in pediatric
patients.
The Development and Validation of Simultaneous Quantitative Analysis
Reversed-phase High-performance Liquid Chromatography for Sitagliptin
Phosphate Monohydrate and Dapagliflozin Propanediol Monohydrate
Fixed-dose Combination Dual-layered Tablet
Authors: Kang So-Jin , Kim Joo-Eun
Published: April 2023

Background:

Sitagliptin phosphate monohydrate-dapagliflozin propanediol hydrate fixeddose
combination (FDC) dual-layered tablet is used for type 2 diabetes treatment. Simultaneous quantitative
analysis can shorten the analysis time of sitagliptin phosphate monohydrate-dapagliflozin propanediol
monohydrate FDC dual-layered tablets and increase their efficiency.

Objective:

This study aimed to develop the simultaneous quantitative analysis for sitagliptin phosphate
monohydrate-dapagliflozin propanediol monohydrate FDC dual-layered tablet, a type 2 diabetes treatment.

Methods:

Simultaneous quantitative analysis using the rapid and selective reversed-phase highperformance
liquid chromatography (RP-HPLC) method was developed and validated using method
validation. RP-HPLC analysis was conducted using an ultraviolent absorption spectrophotometer and
a Zorbax C18 column (4.6 x 150 mm, 5 μm). The flow rate and injection volume were set to 1.5 mL
min-1 and 20 μL, respectively. The wavelength was set at 205 nm.

Results:

The retention times of sitagliptin phosphate monohydrate and dapagliflozin propanediol
monohydrate were 2.28 mins and 10.65 mins, respectively. The relative standard deviations of the
system suitability for validation of simultaneous quantitative analysis were 0.03% for sitagliptin phosphate
monohydrate and dapagliflozin propanediol monohydrate. The chromatogram confirmed that
there was no peak interference between the two main components and between the main component
and the excipients. In addition, It revealed a favorable linearity with correlation coefficients of 0.9999
in the concentration range of 20-120% compared to the standard solution.

Conclusion:

The developed simultaneous quantitative analysis shortened the analysis time and high
efficiency of the sitagliptin phosphate monohydrate-dapagliflozin propanediol monohydrate FDC bilayer
tablet. The validity of the analytical method was verified through accuracy and precision, detection
and quantitation limits, and solution stability tests. In addition, it was thought that it would be
helpful in developing an analytical method by referring to the simultaneous quantitative analysis
method for developing other FDC dual-layered tablets.
Exploring the Advance Data Mining Tool for Optimization of Nanoparticles
Laden in situ Gel for Ocular Drug Delivery
Authors: Shah Purvi , Patel Kesha , Patel Kalpana , Thakkar Vaishali , Dalwadi Saloni , Gandhi Tejal , Bhavsar Bhavesh
Published: April 2023

Background:

Glaucoma is widely treated using eye drops, but around 95% of the drug is
lost by the ocular barrier resulting in low bioavailability. The incorporation of polymeric nanoparticles
into mucoadhesive polymer containing in situ gel is generally helpful in the retention of nanoparticles
on the eye and improves the efficacy of the formulation

Objective:

The objective of the present investigation has to develop polymeric brinzolamide (BRZ)
nanoparticles laden with timolol maleate (TM) in situ gel formulation.

Methods:

The optimized BRZ nanoparticles were prepared using PLGA by nanoprecipitation technique utilizing 32 full factorial designs (FFD). Healthy New Zealand White Rabbit (250-300 g) was
used for the pharmacokinetic and pharmacodynamic study. Design of the experiment was applied to
optimize formulation and validate the model. Some evaluation parameters related to BRZ nanoparticles as well as in-situ gel, have been done

Results:

The results of FFD reveal that the optimized condition for drugs to polymer ratio (1:7) containing 0.98 %w/v for poloxamer 188 results in higher entrapment efficiency and drug release with
156.7 nm particle size. The in-situ gel formulation has been prepared using Gelrite (0.5%w/v), and
HPMC K4M (0.5%w/v) shows acceptable results with sustained drug release up to 6±0.1 h. The rabbit
model's in-vivo pharmacokinetics and pharmacodynamic data showed sustained release of drugs longer than the marketed formulation.

Conclusion:

The proposed formulation could successfully deliver therapeutic concentrations in the
eye with prolonged resident time and serve as a potential alternative for the treatment of glaucoma.
A Patent Review of Human Dihydroorotate Dehydrogenase (hDHODH)
Inhibitors as Anticancer Agents and their Other Therapeutic Applications
(1999-2022)
Authors: Gehlot Pinky , Vyas Vivek K.
Published: April 2023

Highly proliferating cells, such as cancer cells, are in high demand of pyrimidine nucleotides
for their proliferation, accomplished by de novo pyrimidine biosynthesis. The human dihydroorotate
dehydrogenase (hDHODH) enzyme plays a vital role in the rate-limiting step of de novo
pyrimidine biosynthesis. As a recognised therapeutic target, hDHODH plays a significant role
in cancer and other illness. In the past two decades, small molecules as inhibitors hDHODH enzyme
have drawn much attention as anticancer agents, and their role in rheumatoid arthritis (RA),
and multiple sclerosis (MS). In this patent review, we have compiled patented hDHODH inhibitors
published between 1999 and 2022 and discussed the development of hDHODH inhibitors as
anticancer agents. Therapeutic potential of small molecules as hDHODH inhibitors for the treatment
of various diseases, such as cancer, is very well recognised. Human DHODH inhibitors can
rapidly cause intracellular uridine monophosphate (UMP) depletion to produce starvation of pyrimidine
bases. Normal cells can better endure a brief period of starvation without the side effects
of conventional cytotoxic medication and resume synthesis of nucleic acid and other cellular functions
after inhibition of de novo pathway using an alternative salvage pathway. Highly proliferative
cells such as cancer cells do not endure starvation because they are in high demand of nucleotides
for cell differentiation, which is fulfilled by de novo pyrimidine biosynthesis. In addition,
hDHODH inhibitors produce their desired activity at lower doses rather than a cytotoxic dose of
other anticancer agents. Thus, inhibition of de novo pyrimidine biosynthesis will create new prospects
for the development of novel targeted anticancer agents, which ongoing preclinical and
clinical experiments define. Our work brings together a comprehensive patent review of the role
of hDHODH in cancer, as well as various patents related to the hDHODH inhibitors and their anticancer
and other therapeutic potential. This compiled work on patented DHODH inhibitors will
guide researchers in pursuing the most promising drug discovery strategies against the hDHODH
enzyme as anticancer agents.
Assessment of Ergonomic Risk Factors among Metal Sculpture Workers
and Future Scope of AI Applications in Ergonomic Evaluation
Authors: Mishra Yogesh , Singh Ashish Kumar , Meena Makkhan Lal , Dangayach Govind Sharan
Published: April 2023

Background:

Handicraft workers usually carry out daily activities by adopting awkward
postures. The most prevailing health issues among handicraft workers are musculoskeletal disorders
(MSDs).

Objective:

The current research aims to assess the occurrence of musculoskeletal symptoms and
investigate risk factors associated with musculoskeletal disorders among metal sculpture artisans.
Subsequently, the study highlighted the future scope of AI applications in ergonomic evaluation.

Methods:

144 male metal sculpture workers participated in the study. A modified Nordic questionnaire
was adopted to determine the musculoskeletal problems among metal sculpture workers. The
probable risk elements for MSD symptoms were identified by applying binary logistic regression.

Results:

Most workers faced discomfort in various body parts, particularly the wrist, lower back,
and shoulders. The outcome of the logistic regression model revealed that job-related factors have
significantly contributed to the development of MSD symptoms.

Conclusion:

This study concedes that awkward working postures for prolonged periods highly affect
the health of metal sculpture workers, and there is a need for ergonomic intervention to minimize
the risks of musculoskeletal disorders. The study also emphasizes the future scope of Artificial
Intelligence (AI) applications that can be used in ergonomically assessing working postures.
Evidence and Prospects of Lycopene as Powerful Red Superfood: Modern
Approach to Food Science
Authors: Gupta Ena , Mishra Pragya , Singh Priyanka , Mishra Neha
Published: April 2023

Lycopene is a plant-derived important nutrient belonging to a group of pigments identified
as carotenoids. Lycopene has distinctive chemical and structural features contributing to definite
biological properties. Lycopene is a powerful antioxidant and prevents cells and tissues from
damage caused by singlet oxygen or free radicals. Research studies have shown the healthpromoting
potential of lycopene or its metabolites in the prevention of chronic diseases like diabetes,
cancer, asthma, metabolic syndrome, arthritis, and cardiovascular diseases. Lycopene is stable
for processing like other natural compounds when present in the plant tissue matrix. Over the last
few years, the global lycopene market has increased in different sectors like pharmaceuticals, cosmetics,
food and dairy products, and other dietary supplements. The most important aspect of lycopene
as a superfood is its synergistic nature with other nutrients. The main aim of this review article
is to study chemistry, biosynthetic pathways, biotransformation, sources, and acceptable daily intake.
Its characterization as a superfood, therapeutic potential, and wide range of applications in the
food industry are also studied.
A Comprehensive Review on Biological and Chemical Diversity inAesculusL. Genus (Sapindaceae)
Authors: Shah Mamta , Shah Rutvi , Salot Dhyey , Shah Dhvani , Shah Dhruvil , Shah Rajvi , Verma Preeti
Published: April 2023

Aesculus L. is a genus of 12 to 19 woody species, representing one of the most acclaimed examples of inter-continental incoherence of the plants native to temperate regions of the Northern Hemisphere. It is traditionally valued in Ayurveda and the Chinese system of medicine for its various species that possess antitumor, cardioprotective, anti-inflammatory and neuroprotective activities. Current studies on this genus have revealed the presence of specific saponins with a multispectrum of pharmacological actions and therapeutic applications. A repertoire of literature related to the biological, taxonomical, phytochemical and ethnopharmacological aspects of Aesculus genus and its uses in different indigenous populations was explored. An inventory of all the species of this genus that were found to be useful as per ethnopharmacological literature was prepared. The ethnobotany, phytochemistry and pharmacology of the individual species are outlined in this review. The extensive information cited here has adduced the likely areas where the important species of this genus can illustrate significant therapeutic intervention in the management of chronic disorders including diabetes, hypercholesterolemia and cancer. The wide range of its pharmacological actions is attributed to the distinct phytochemicals occurring in the species, especially the triterpenoidal saponins like aescin. This review amplifies the recent studies on phytochemical and pharmacological aspects, which alludes that these species have noteworthy therapeutic potential.
A Comprehensive Review of Cosmeceutical Chemistry
Authors: Kushwaha Neelottama , Kushwaha Swatantra K.S.
Published: April 2023

The confluence of three key fields, namely, cosmetics, pharmaceutics, and the chemistry
of cosmetic items with the human body system, is known as cosmeceutical chemistry. The
most remarkable logical knowledge and innovation are incorporated into cosmetology, including
science, pharmacology, subatomic physics and nervous system science, etc. Cosmetics are items
created to beautify, protect, and change the appearance of our bodies' external features. Water,
emulsifiers, preservatives, thickeners, moisturizing agents, colors, and perfumes are the main
components found in the majority of cosmetics. Ingredients may be synthetic or naturally occurring,
but how they may affect our health mostly depends on the chemical substances they are
made of. The concentrations of potentially harmful compounds present in cosmetics are thought to
be too low to endanger human health. Nowadays, various types of cosmetics are available in the
market such as lotions, lipstick, colognes, nail paints, and other products. After using the base
cream, various cosmetics, such as face powder, provide skin luster. To achieve detergency, wetting,
emulsifying, re-coloring, and moderating effects, cosmetic fixings/excipients are used. Some
unfriendly synthetic reactions in the preparation of cosmetics cause serious dangerous effects on
people and the environment. The usage of several cosmetics has restorative effects. Once more,
each population has a specific makeup of cosmetic users. The distinction between cosmetic and
medical research is becoming increasingly blurred as a result of this growing application of science
to beauty. Leading cosmetic companies' laboratories conduct cutting-edge research in areas
like grid science, cell reinforcements, and mature forms. Their manufacturing, marketing, and delivery
should all be subject to proper rules and regulations in addition to pricing.
The Impact of ESG Scores on Corporate Financial Performance: Moderating Role of Gender Diversity
Authors: Setiani Eko Putri
Published: April 2023

ABSTRACTThis study aims to examine the impact of environmental, social, and governance (ESG) scores on corporate financial performance and the moderating role of gender diversity in this relationship. This study uses 80 samples of companies listed on the Indonesian stock exchange. Samples were taken using a purposive sampling approach. The hypothesis was tested using multiple regression analysis. The results of this research show that there is a positive relationship between ESG scores and corporate financial performance. Gender diversity fosters a positive relationship between ESG scores and corporate financial performance.  Investors need not only pay attention to financial aspects but also pay attention to environmental, social, and governance aspects as non-financial factors in making investment decisions.Keywords: ESG Scores, Financial Performance, Gender DiversityABSTRAKPenelitian ini bertujuan untuk menguji dampak skor environmental, social dan governance (ESG) terhadap kinerja keuangan perusahaan. Penelitian ini menggunakan 80 sampel perusahaan yang terdaftar di bursa efek Indonesia. Sampel diambil menggunakan pendekatan purposive sampling. Variabel dependen dalam penelitian ini adalah kinerja keuangan perusahaan, variabel independen adalah skor ESG, variabel pemoderasi adalah keragaman gender, dan variabel kontrol dalam penelitian ini adalah ukuran perusahaan, leverage dan growth. Hipotesis penelitian diuji menggunakan analisis regresi berganda. Hasil penelitian menunjukkan adanya hubungan yang positif antara skor ESG dan kinerja keuangan perusahaan. Keragaman gender dapat memperkuat hubungan antara ESG dan kinerja keuangan perusahaan. Investor tidak hanya perlu untuk memperhatikan aspek keuangan saja tetapi juga perlu memperhatikan aspek lingkungan, sosial dan tata kelola sebagai faktor non keuangan dalam pengambilan keputusan investasi.Kata Kunci: ESG Skor, Kinerja Keuangan, Keragaman Gender, Tata Kelola
Вязкоупругие свойства углепластиков на основе порошковых полиимидных связующих
Authors: Ваганов Г.В. , Диденко А.Л. , Мягкова Л.А. , Елоховский В.Ю. , Попова Е.Н. , Юдин В.Ю.
Published: April 2023

Carbon fiber reinforced plastics based on thermoplastic partially crystalline fusible polyimide R-BAPB and oligoimide IDA (diacetyl imide) have been obtained. The thermal, thermomechanical and mechanical properties of carbon plastics based on polyimides have been studied. It has been shown that carbon plastics based on the used polyimide binders have increased crack resistance, which makes it possible to operate them at temperatures up to ~400oC.
Implementing a Digital Depression Prevention Program in Australian Secondary Schools: Cross-Sectional Qualitative Study
Authors: Beames Joanne R , Werner-Seidler Aliza , Hodgins Michael , Brown Lyndsay , Fujimoto Hiroko , Bartholomew Alexandra , Maston Kate , Huckvale Kit , Zbukvic Isabel , Torok Michelle , Christensen Helen , Batterham Philip J , Calear Alison L , Lingam Raghu , Boydell Katherine M
Published: April 2023

Background

Depression is common during adolescence and is associated with adverse educational, employment, and health outcomes in later life. Digital programs are increasingly being implemented in schools to improve and protect adolescent mental health. Although digital depression prevention programs can be effective, there is limited knowledge about how contextual factors influence real-world delivery at scale in schools.

Objective

The purpose of this study was to examine the contextual factors that influence the implementation of the Future Proofing Program (FPP) from the perspectives of school staff. The FPP is a 2-arm hybrid type 1 effectiveness-implementation trial evaluating whether depression can be prevented at scale in schools, using an evidence-based smartphone app delivered universally to year 8 students (13-14 years of age).

Methods

Qualitative interviews were conducted with 23 staff from 20 schools in New South Wales, Australia, who assisted with the implementation of the FPP. The interviews were guided by our theory-driven logic model. Reflexive thematic analysis, using both deductive and inductive coding, was used to analyze responses.

Results

Staff perceived the FPP as a novel (“innovative approach”) and appropriate way to address an unmet need within schools (“right place at the right time”). Active leadership and counselor involvement were critical for planning and engaging; teamwork, communication, and staff capacity were critical for execution (“ways of working within schools”). Low student engagement and staffing availability were identified as barriers for future adoption and implementation by schools (“reflecting on past experiences”).

Conclusions

Four superordinate themes pertaining to the program, implementation processes, and implementation barriers were identified from qualitative responses by school staff. On the basis of our findings, we proposed a select set of recommendations for future implementation of digital prevention programs delivered at scale in schools. These recommendations were designed to facilitate an organizational change and help staff to implement digital mental health programs within their schools.

International Registered Report Identifier (IRRID)

RR2-10.1136/bmjopen-2020-042133
The Goldilocks Dilemma in mHealth Interventions: Balancing User Response and Reflection (Preprint)
Authors: Nelson Lyndsay A. , Spieker Andrew J. , LeStourgeon Lauren M. , Greevy Robert A. , Molli Samuel , Roddy McKenzie K. , Mayberry Lindsay S.
Published: April 2023

BACKGROUND

mHealth has the potential to radically improve health behaviors and quality of life; however, there are still key gaps in understanding how to optimize mHealth engagement. Most engagement research reports only on system use without consideration of whether the user is reflecting on the content cognitively. Although interactions with mHealth are critical, cognitive investment is also important for meaningful behavior change. Importantly, content designed to request too much reflection, may lead users to disengage. Understanding how to strike the balance between response and reflection burden has critical implications for achieving effective engagement to impact intended outcomes.

OBJECTIVE

We sought to understand the interplay between response burden and reflection burden for impacting mHealth engagement. Specifically, we examined how varying the response and reflection burden of mHealth content would impact users’ text message response rate as part of an mHealth intervention.

METHODS

We recruited support persons of people with diabetes for a randomized controlled trial (RCT) evaluating an mHealth intervention for diabetes management. Support person participants assigned to the intervention (N=148) completed a survey and received text messages for 9 months. During the two-year RCT, we sent four versions of a weekly interactive text message that varied in reflection and response burden. We quantified engagement using response rate. We compared the odds of responding to each text and estimated associations between participant characteristics and response rate.

RESULTS

Results: The texts requesting the most reflection had the lowest response rates (median 10-23%), regardless of response burden. Response rate was highest for the text requesting the least reflection (90%), yet still relatively high for the text with medium reflection (75%). Lower odds of responding were associated with higher reflection burden (P<.001). Participants who were younger or had lower socioeconomic status had lower response rates to texts with more reflection burden relative to their counterparts (P<.01 for each).

CONCLUSIONS

Conclusions: As reflection burden increased, engagement decreased, and we found more disparities in engagement by participants’ characteristics. Content encouraging moderate levels of reflection may be ideal for achieving both cognitive investment and system use. Our findings provide insights into mHealth design and optimizing both engagement and effectiveness.

CLINICALTRIAL

NCT04347291
A Randomized Controlled Trial Examining Parent-Child Play as an Adjunct to Biofeedback Game-Based Emotion Regulation Learning (Preprint)
Authors: Wintner Suzanne , Peechatka Alyssa , Kahn Jason
Published: April 2023

BACKGROUND

Emotion regulation (ER) skill-building is important to child development and behavioral health. Evidence-based digital emotion regulation learning tools are available for in-home use, including single-player game-based interventions. Parent-child interactive interventions also have demonstrated effectiveness in child emotion regulation learning.

OBJECTIVE

The current study examines the effects of an evidence-based single-player emotion regulation skill building biofeedback video game on child irritability and parent-child relationship, when used alone and with adjunctive parent-child structured play.

METHODS

Forty-one parent-child dyads participated in a randomized controlled trial comparing a group of child participants who played only online ER learning biofeedback video games to a group of child participants who played online ER learning biofeedback video games and additionally, with a participating parent, played interactive offline games with ER learning biofeedback elements.

RESULTS

We found that playing online ER learning biofeedback video games resulted in statistically significant reductions in irritability and child-parent conflict for child and parent study participants, regardless of group assignment. Over 90% of parents reported improvements in their child’s overall emotion regulation.

CONCLUSIONS

This study contributes to evidence that at-home digital mental health interventions can be effective. Further study is needed to explore factors contributing to parent-child emotional and relational dynamics and to develop effective evidence-based parent-child interactive interventions for at-home use.

CLINICALTRIAL

Trial Registration: ClinicalTrials.gov NCT05080647
Prototype of an App Designed to Support Self-Management for Health Behaviors and Weight in Women Living With Breast Cancer: Qualitative User Experience Study (Preprint)
Authors: Lally Phillippa , May Christine N , Mitchell E Siobhan , McCallum Meaghan , Michaelides Andreas , Fisher Abigail
Published: April 2023

BACKGROUND

Accessible self-management interventions are required to support people living with breast cancer.

OBJECTIVE

This was an industry-academic partnership study that aimed to collect qualitative user experience data of a prototype app with built-in peer and coach support designed to support the management of health behaviors and weight in women living with breast cancer.

METHODS

Participants were aged ≥18 years, were diagnosed with breast cancer of any stage within the last 5 years, had completed active treatment, and were prescribed oral hormone therapy. Participants completed demographic surveys and were asked to use the app for 4 weeks. Following this, they took part in in-depth qualitative interviews about their experiences. These were analyzed using thematic analysis.

RESULTS

Eight participants (mean age, 45 years; mean time since diagnosis, 32 months) were included. Of the 8 participants, 7 (88%) were white, 6 (75%) had a graduate degree or above, and 6 (75%) had stage I-III breast cancer. Four overarching themes were identified: (1) Support for providing an app earlier in the care pathway; (2) Desire for more weight-focused content tailored to the breast cancer experience; (3) Tracking of health behaviors that are generally popular; and (4) High value of in-app social support.

CONCLUSIONS

This early user experience work showed that women with breast cancer found an app with integrated social and psychological support appealing to receive support for behavior change and weight management or self-management. However, many features were recommended for further development. This work is the first step in an academic-industry collaboration that would ultimately aim to develop and empirically test a supportive app that could be integrated into the cancer care pathway.