bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Current Rules and Regulations for Preclinical Studies of Radiopharmaceuticals
Authors: Lunev A. S. , Petrosova K. A. , Ternovskaya K. E. , Sklyarenko A. D. , Surnina A. E. , Nigmatulina А. I. 
Published: February 2024

SCIENTIFIC RELEVANCE. Owing to specific aspects of their development and use, radiopharmaceuticals require separate rules and regulations for preclinical studies. However, current legislation and regulations on the organisation and conduct of preclinical studies of radiopharmaceuticals contain a number of contradictions and need improvement.AIM. This review aimed to analyse the rules and regulations governing preclinical studies of radiopharmaceuticals in the Russian Federation and abroad.DISCUSSION. The regulatory requirements for preclinical studies of radiopharmaceuticals that are conducted by specialised institutions in Russia and abroad have several shortcomings and inconsistencies. Laboratories working with animals and open sources of ionising radiation should prioritise regulations related to radiation safety. Radiation safety requirements should be in line with the sanitary standards and practical guidelines used in preclinical studies. This review covers the specific aspects of conducting preclinical studies of therapeutic and diagnostic radiopharmaceuticals. According to the review results, international guidelines for preclinical studies of radiopharmaceuticals focus on systematising the applicable requirements and aim at providing a consistent approach to preclinical studies to reduce the conduct of studies that are not informative for a specific radiopharmaceutical product.CONCLUSIONS. Radiation safety requirements should be harmonised with international guidelines. Methodological recommendations and local regulations should be developed and approved to facilitate the resolution of regulatory issues related to the organisation and conduct of preclinical studies of radiopharmaceuticals. Many medical, social, technical, and administrative issues need addressing at the inter-institutional and/or national level.
Pharmacy Compounding Regulation in the German Pharmaceutical Market. Part 1. Basic Regulatory Provisions (Review)
Authors: Erdni-Garyaev S. E. , Mamedov D. D. , Yurochkin D. S. , Zelikova D. D. , Golant Z. M. , Fisenko V. S. , Narkevich I. A. 
Published: February 2024

SCIENTIFIC RELEVANCE. There is a need to move towards an appropriate system of quality assurance in pharmacy compounding. At the same time, the development of a Russian regulatory system for pharmacy compounding requires a broad understanding of international experience.AIM. This study aimed at analysing the basic principles of pharmacy compounding regulation in the Federal Republic of Germany in order to identify best practices and determine ways to improve the legal and regulatory framework for compounding pharmacies in the Russian Federation.DISCUSSION. According to German law, pharmacies may dispense compounded medicinal products on an oral request from a patient. The German regulatory framework provides a mechanism delineating medicinal products compounded by pharmacies and those manufactured by pharmaceutical companies. The geographical and quantitative restrictions combined with the neutral pricing policy for pharmacies facilitate the establishment of a highly effective pharmaceutical supply system. In practice, this system helps set uniform prices for medicinal products throughout Germany while preventing pharmacy chains from monopolising the pharmaceutical market. These regulations can be considered regulatory mechanisms operating at the regional (land) level. Moreover, it is of key importance that German legislation divides compounded medicinal products into stock and extemporaneous preparations.CONCLUSIONS. German pharmaceutical practice features a number of innovations that can be borrowed for Russian pharmaceutical practice. Russian pharmaceutical legislation may benefit from adopting the concept of a “request from an individual” for dispensing compounded medicinal products that do not contain prescription-only active pharmaceutical ingredients (APIs). In order to improve the efficiency of the use of pharmaceutical-quality raw materials, including APIs, it is necessary to identify cases in which regular pharmacies can receive or purchase compounded medicinal products from compounding pharmacies and cases in which compounding pharmacies can purchase APIs from other compounding pharmacies. The authors recommend considering the possibility of defining the role, functions, and powers of self-regulating professional pharmacy organisations at various levels of governance in this social sphere of activity. Furthermore, the authors recommend creating a Russian mechanism to mitigate the risks of stock shortages and/or limited supply of medicinal products that would be similar to the German “standard authorisation” system and would encompass compounding pharmacies and pharmaceutical companies.
Rebel Patients and Caregivers Podcast
Authors: Fox Susannah , Bell, RN, MSN, MHA Sarah , Sakumoto, MD, CMIO Matthew 
Published: February 2024

Patients are creating solutions and setting new standards for what’s possible in health and outcomes. Speakers discuss perspectives and viewpoints in patient care that help both clinicians, patients, survivors, and caregivers learn valuable new skills, and how to deploy them to work together, and take power back.
Discussion Topics

Providing guidance for those suffering from new diagnosis or chronic conditions on how to leverage patient-led groups to find answers and change their course of care
Clinician experiences with patient-led groups and patient-led healthcare
Learn about the four patient archetypes – Seeker, Networker, Solver, and Champion
Advice for patients, caregivers, and survivors who want to learn how to navigate roadblocks and the lack of information in their healthcare journey
Advice for how “Seekers” can get started
Clinicians advice on facing unknowns to patients and how to navigate the healthcare system
Concerns about potential misinformation in patient and caregiver-led groups
Data on patients self-regulating and accuracy of reports
Turning to online sources such as “Dr. Google” or patient-led groups for information

Where will this revolution take us in the next 5-10 years? Begin the learning journey in Part 1 of this series.
Additive and Multiplicative Operations on Set of Polygonal Numbers
Authors: Srinivas Thiruchinapalli 
Published: February 2024

In this paper, the focus on generating k-gonal numbers P (k, n) \(=\) \(\left\{ \begin{array}{r} \frac{\mathbf{n}}{\mathbf{2}}\left\lbrack \left( \mathbf{k - 3} \right)\left( \mathbf{n - 1} \right)\mathbf{+}\left( \mathbf{n + 1} \right) \right\rbrack\mathbf{\ for\ k > 2,n \geq 0} \\ \frac{\mathbf{n}}{\mathbf{2}}\left\lbrack \left( \mathbf{k - 3} \right)\left( \mathbf{n + 1} \right)\mathbf{+}\left( \mathbf{n - 1} \right) \right\rbrack\mathbf{\ for\ k > 2,n < 0} \end{array} \right\}\). Also introduce to define additive (+) and multiplicative (*) operations on Sets of k-gonal numbers. In particular, concerning addition (+), \(\mathbf{p}\left( \mathbf{k,m} \right)\mathbf{+ p}\left( \mathbf{k,n} \right)\mathbf{= p}\left( \mathbf{k,m + n} \right)\mathbf{-}\left( \mathbf{k - 2} \right)\mathbf{mn\ \ }forsome\ integer\mathbf{\ k > 2}\). Also, concerning multiplication (*), \(\mathbf{p}\left( \mathbf{k,m} \right)\mathbf{*p}\left( \mathbf{k,n} \right)\mathbf{= p}\left( \mathbf{k,mn} \right)\mathbf{+}\frac{\left( \mathbf{k - 4} \right)\left( \mathbf{k - 2} \right)\mathbf{mn}}{\mathbf{4}}\left( \mathbf{m - 1} \right)\left( \mathbf{n - 1} \right)\mathbf{\ }forsome\ integer\mathbf{\ \ k > 2}\).Also, summation of any two different k-gonal is \(\mathbf{p}\left( \mathbf{k}_{\mathbf{1}}\mathbf{,n} \right)\mathbf{+ p}\left( \mathbf{k}_{\mathbf{2}}\mathbf{,n} \right)\mathbf{= n}\left( \mathbf{n + 1} \right)\mathbf{+}\frac{\mathbf{n}\left( \mathbf{n - 1} \right)}{\mathbf{2}}\left\lbrack \left( \mathbf{k}_{\mathbf{1}}\mathbf{+}\mathbf{k}_{\mathbf{2}} \right)\mathbf{- 6} \right\rbrack\mathbf{\ for\ }\mathbf{k}_{\mathbf{1}}\mathbf{,}\mathbf{k}_{\mathbf{2}}\mathbf{> 2}\).

Also, I applied above properties on some Sets of Polygonal numbers, which are generated by replacing integer k with 3,4,5,6,7 and 8. Also, introduced to study of Repeated steps of Residues of the above Sets of Polygonal numbers generated by k with 3,4,5,6,7 and 8.
Importance of pollinator diversity for sunflower seed production
Authors: Shpak Y. V. , Leheta U. V. , Sosnovskyi K. S. 
Published: February 2024

The sunflower (Helianthus annuus Linnaeus) is one of the most important food crops in the world. In modern agroecology, this pivotal plant is deeply intertwined with diverse pollination mechanisms. This study elucidates the multifaceted contributions of various pollinator taxa, delving into their respective efficiencies and behaviors vis-à-vis sunflower reproductive success. The honeybee (Apis mellifera Linnaeus, 1758) plays a central role in sunflower pollination, transferring pollen over large distances, thereby bolstering the genetic diversity of sunflower populations. While sunflowers derive immense benefits from honeybee pollination, they reciprocally offer their pollen as vital nutrition for bee larvae. However, this symbiotic relationship is nuanced, with honeybees occasionally exhibiting selectivity based on sunflower cultivar. While honeybees are paramount, the richness of the ecosystem is further accentuated by the presence of other pollinators, each contributing uniquely to the sunflower’s lifecycle. The foraging fidelity of solitary bees, such as the leafcutter bee (Megachile spp.) and mason bee (Osmia spp.), underscores their indispensable role in cross-pollination. Bumblebees (Bombus spp.) introduce a fascinating "buzz pollination" mechanism, leveraging vibrations to optimize pollen release. Simultaneously, wasps provide functions beyond pollination, serving as biocontrol agents by preying on detrimental pests. Surprisingly, mosquitoes appeared to also be contributors to pollination, especially when traditional pollinators are scarce, with their nocturnal tendencies augmenting pollination continuity. Hoverflies render dual benefits: they aid in pollination and their larvae predate on pests. While butterflies are primarily nectar-oriented, they inadvertently partake in pollen transfer. Moths, through their nocturnal activities, complement pollination. Beetles, often overlooked, act as secondary pollinators. Regrettably, contemporary agricultural practices often disrupt this ecological equilibrium. Pervasive pesticide use and habitat fragmentation imperil these pollinators, underscoring the urgent need for pollinator-friendly approaches. As climate conditions fluctuate, understanding these pollinator dynamics becomes increasingly critical. This comprehensive examination advocates for holistic conservation strategies, targeting sustained sunflower yields and broader ecosystem resilience.
Exploring pyrrolidinyl-spirooxindole natural products as promising platforms for the synthesis of novel spirooxindoles as EGFR/CDK2 inhibitors for halting breast cancer cells
Authors: Nafie Mohamed S. , Al-Majid Abdullah Mohammed , Ali M. , Alayyaf Abdulmajeed Abdullah , Haukka Matti , Ashraf Sajda , Ul-Haq Zaheer , El-Faham Ayman , Barakat Assem 
Published: February 2024

Cancer represents a global challenge, and the pursuit of developing new cancer treatments that are potent, safe, less prone to drug resistance, and associated with fewer side effects poses a significant challenge in cancer research and drug discovery. Drawing inspiration from pyrrolidinyl-spirooxindole natural products, a novel series of spirooxindoles has been synthesized through a one-pot three-component reaction, involving a [3 + 2] cycloaddition reaction. The cytotoxicity against breast cancer cells (MCF-7 and MDA-MB-231) and safety profile against WISH cells of the newly developed library were assessed using the MTT assay. Compounds 5l and 5o exhibited notable cytotoxicity against MCF-7 cells (IC50 = 3.4 and 4.12 μM, respectively) and MDA-MB-231 cells (IC50 = 8.45 and 4.32 μM, respectively) compared to Erlotinib. Conversely, compounds 5a-f displayed promising cytotoxicity against MCF-7 cells with IC50 values range (IC50 = 5.87–18.5 μM) with selective activity against MDA-MB-231 cancer cells. Compound 5g demonstrated the highest cytotoxicity (IC50 = 2.8 μM) among the tested compounds. Additionally, compounds 5g, 5l, and 5n were found to be safe (non-cytotoxic) against WISH cells with higher IC50 values ranging from 39.33 to 47.2 μM. Compounds 5g, 5l, and 5n underwent testing for their inhibitory effects against EGFR and CDK-2. Remarkably, they demonstrated potent EGFR inhibition, with IC50 values of 0.026, 0.067, and 0.04 μM and inhibition percentages of 92.6%, 89.8%, and 91.2%, respectively, when compared to Erlotinib (IC50 = 0.03 μM, 95.4%). Furthermore, these compounds exhibited potent CDK-2 inhibition, with IC50 values of 0.301, 0.345, and 0.557 μM and inhibition percentages of 91.9%, 89.4%, and 88.7%, respectively, in contrast to Roscovitine (IC50 = 0.556 μM, 92.1%). RT-PCR analysis was performed on both untreated and 5g-treated MCF-7 cells to confirm apoptotic cell death. Treatment with 5g increased the gene expression of pro-apoptotic genes P53, Bax, caspases 3, 8, and 9 with notable fold changes while decreasing the expression of the anti-apoptotic gene Bcl-2. Molecular docking and dynamic simulations (100 ns simulation using AMBER22) were conducted to investigate the binding mode of the most potent candidates, namely, 5g, 5l, and 5n, within the active sites of EGFR and CDK-2.
Comparative efficacy of anthropometric indices in predicting 10-year ASCVD risk: insights from NHANES data
Authors: Tang Li , Zeng Ling 
Published: February 2024

BackgroundCardiovascular diseases remain a leading cause of morbidity and mortality worldwide. Accurately predicting the 10-year risk of Atherosclerotic Cardiovascular Disease (ASCVD) is crucial for timely intervention and management. This study aimed to evaluate the predictive performance of six anthropometric indices in assessing the 10-year ASCVD risk.MethodsUtilizing data from the National Health and Nutrition Examination Survey (NHANES) database (1999–2018), the study involved 11,863 participants after applying exclusion criteria. Six anthropometric indices—waist circumference (WC), body mass index (BMI), waist-to-height ratio (WHtR), a body shape index (ABSI), body roundness index (BRI), and waist-to-height0.5 ratio (WHT.5R)—were calculated. The 10-year ASCVD risk was assessed using the 2013 ACC/AHA guidelines &amp; pooled cohort equations model. Participants were divided into two groups based on an ASCVD risk threshold of 7.5%. Statistical analysis included chi-square tests, odds ratios, and receiver operating characteristic (ROC) curves.ResultsThe study found significant differences in baseline characteristics between participants with ASCVD risk less than 7.5% and those with a risk greater than or equal to 7.5%, stratified by gender. In both male and female groups, individuals with higher ASCVD risk exhibited higher age, waist circumference, BMI, and a higher prevalence of health-compromising behaviors. ABSI emerged as the most accurate predictor of ASCVD risk, with the highest area under the curve (AUC) values in both genders. The optimal cut-off values for ABSI was established for effective risk stratification (cut-off value = 0.08).ConclusionThe study underscores the importance of anthropometric indices, particularly ABSI, in predicting the 10-year risk of ASCVD. These findings suggest that ABSI, along with other indices, can be instrumental in identifying individuals at higher risk for ASCVD, thereby aiding in early intervention and prevention strategies.
Case report: Whole exome sequencing identified a novel mutation (p.Y301H) of MAF in a Chinese family with congenital cataracts
Authors: Lin Zhao-Jing , Long Jie-Yi , Li Juan , Wang Fang-Na , Chu Wei , Zhu Lei , Li Ya-Li , Fan Liang-Liang 
Published: February 2024

BackgroundCongenital cataracts stand as the primary cause of childhood blindness globally, characterized by clouding of the eye’s lens at birth or shortly thereafter. Previous investigations have unveiled that a variant in the V-MAF avian musculoaponeurotic-fibrosarcoma oncogene homolog (MAF) gene can result in Ayme-Gripp syndrome and solitary cataract. Notably, MAF mutations have been infrequently reported in recent years.MethodsIn this investigation, we recruited a Chinese family with non-syndromic cataracts. Whole exome sequencing and Sanger sequencing were applied to scrutinize the genetic anomaly within the family.ResultsThrough whole exome sequencing and subsequent data filtration, a new mutation (NM_005360, c.901T&gt;C/p.Y301H) in the MAF gene was detected. Sanger sequencing validated the presence of this mutation in another affected individual. The p.Y301H mutation, situated in an evolutionarily preserved locus, was not detected in our 200 local control cohorts and various public databases. Additionally, multiple bioinformatic programs predicted that the mutation was deleterious and disrupted the bindings between MAF and its targets.ConclusionHence, we have documented a new MAF mutation within a Chinese family exhibiting isolated congenital cataracts. Our study has the potential to broaden the spectrum of MAF mutations, offering insights into the mechanisms underlying cataract formation and facilitating genetic counseling and early diagnosis for congenital cataract patients.
Role of serum neuron-specific enolase levels in the early diagnosis and prognosis of sepsis-associated encephalopathy: a systematic review and meta-analysis
Authors: Pei MengQin , Yang YuShen , Zhang ChunYan , Huang QiaoMei , Fang YuMing , Xu LiMing , Lin Shu , He HeFan 
Published: February 2024

BackgroundSepsis-associated encephalopathy (SAE) is one of the most ubiquitous complications of sepsis and is characterized by cognitive impairment, poor prognosis, and a lack of uniform clinical diagnostic criteria. Therefore, this study investigated the early diagnostic and prognostic value of serum neuron-specific enolase (NSE) in SAE.MethodsThis systematic review and meta-analysis systematically searched for clinical trials with serum NSE information in patients with sepsis in the PubMed, Web of Science, Embase, and Cochrane databases from their inception to April 10, 2023. Included studies were assessed for quality and risk of bias using The Quality Assessment of Diagnostic Accuracy-2 tool. The meta-analysis of the included studies was performed using Stata 17.0 and Review Manager version 5.4.FindingsEleven studies were included in this meta-analysis involving 1259 serum samples from 947 patients with sepsis. Our results showed that the serum NSE levels of patients with SAE were higher than those of the non-encephalopathy sepsis group (mean deviation, MD,12.39[95% CI 8.27–16.50, Z = 5.9, p &lt; 0.00001]), and the serum NSE levels of patients with sepsis who died were higher than those of survivors (MD,4.17[95% CI 2.66–5.68, Z = 5.41, p &lt; 0.00001]).ConclusionElevated serum NSE levels in patients with sepsis are associated with the early diagnosis of SAE and mortality; therefore, serum NSE probably is a valid biomarker for the early diagnosis and prognosis of patients with SAE.Systematic review registrationThis study was registered in PROSPERO, CRD42023433111.
The relationship between dietary inflammatory index and metabolic syndrome and its components: a case study in Kashi urban, Xinjiang
Authors: Zhang Yangyi , Liu Xiangtao , Su Yinxia , Jiang Yan , Cai Junxiu , Yang Xiaoping , Zou Yuan , Chen Jing , Zhao Xingyang , Xiao Hui 
Published: February 2024

IntroductionThis paper examines the association between the dietary inflammatory index (DII) and the risk of metabolic syndrome (MS) and its components among Uygur adults in Kashi, Xinjiang.MethodsThe study used the multi-stage random cluster sampling method to investigate the adult residents of Uighu aged over 18 years old in one county and one township/street of three cities in Kashi between May and June 2021. All dietary data collected were analyzed for energy and nutrient intake with a nutritional analysis software, followed by a calculation of DII. Logistic regression was used to estimate the association between DII and the risks of MS and its components.ResultsThe maximum DII value across our 1,193 respondents was 4.570 to 4.058, with an average value of 0.256. When we analyzed the DII as a continuous variable, we determined the anti-inflammatory diet has been identified as a mitigating factor for metabolic syndrome (OR = 0.586, 95% CI = 0.395–0.870), obesity (OR = 0.594, 95% CI = 0.395–0.870), elevated fasting glucose levels (OR = 0.422, 95% CI = 0.267–0.668), and hypertension (OR = 0.698, 95% CI = 0.488–0.996). When the model was adjusted by sex, age, and occupation, we found a significant correlation between high- and low-density lipoproteinemia and DII (OR = 1.55, 95% CI = 1.040–2.323). The present study identified four distinct dietary patterns among the population under investigation. There was a linear trend in the incidence of MS and hypertension across low, middle, and high levels of fruits and milk dietary pattern model (p = 0.027; p = 0.033), within this dietary pattern may serve as protective factors against MS and hypertension, suggesting that fruits and milk within this dietary pattern may serve as protective factors against MS and hypertension. And the linear trend in the incidence of elevated fasting glucose and obesity across the low, medium, and high scores of meet and eggs dietary pattern (p = 0.006; p &lt; 0.001), suggest that a diet rich in meat may potentially contribute to an increased risk of developing elevated fasting glucose levels and obesity. An observed linear trend in the incidence rate of high fasting blood glucose across low, moderate, and high scores of dried fruits and nuts dietary pattern (p = 0.014), indicating that increased consumption of nuts acted as a protective factor against elevated fasting blood glucose levels and contributed to their reduction.DiscussionThe dietary inflammation index was integrated with the findings from the study on the dietary patterns of the sampled population, revealing that an anti-inflammatory diet demonstrated a protective effect against metabolic syndrome, obesity, high fasting blood glucose, and hypertension in this specific population. laying the foundation for further research.