bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Breast Tumors With Image Processing Using Canny Edge Detection
Authors: Triwibowo Deny Nughoro , Dewa Bala Putra , Sumantri R Bagus Bambang , Suryani Riska
Published: March 2023

Breast tumor is one of the leading causes of death in women worldwide. The term tumor is often used for all lumps found in the human body. The increase in the number of cases of breast tumors that occur each year is due to the absence of prevention or early detection. The research was carried out by utilizing the development of information technology to create a breast tumor detection system with digital image processing. The application system will process mammogram images to detect edges with the canny method and will be classified using the SVM method. The data used is 176 data obtained from the Kaggle dataset. The test results revealed that 64 patients were classified as having malignant breast tumors (M), and 113 did not have breast tumors (B), with a classification accuracy rate of 95%. From the results obtained, the application system is very good for the early identification of breast tumors.
Legal Aspects of Telemedicine Health Services in the Perspective of Health Law in Indonesia in the Digital Era
Authors: Afrilies Marlia Hafny , Naili Yuris Tri
Published: March 2023

Information Technology that develops rapidly over time has brought significant influence on the way of communicating and the activities of society globally. The health sector is no exception, and the peak is during the Covid-19 pandemic which greatly affects community interactions both individually and with health workers. One of the ways health workers respond to the pandemic period is by utilizing the information technology system optimally to improve the quality of medical services so that people continue to get health services as they should. This article will discuss the development of rules for telemedicine health services in health law in Indonesia, and the extent to which they provide legal protection for health service users and health workers as health care providers. The research method used in this study, namely Normative Juridical Research, is a legal research method carried out by examining library materials or secondary materials. The result of the discussion is legal obligations, which are strengthened by legal sanctions, aiming to realize legal certainty. However, this legal certainty should also consider the expediency of the law so that the law does not only provide legal certainty, but also provides legal benefits, namely the equitable distribution of quality health services to remote parts of the Indonesian state
Melatonin as preemptive analgesic for intraoperative pain
Authors: Katariya Chanchal
Published: March 2023

Several anti-inflammatory and analgesic drugs have been used to reduce pain and discomfort during periodontal surgeries. This study evaluates the efficacy of using melatonin and ketorolac for pain prevention during open-flap debridement surgery. This prospective randomized controlled trial was performed in patients who presented with chronic periodontitis after non-surgical periodontal therapy, requiring flap surgery. Group 1: Flap surgery following non-surgical periodontal therapy after one month with no oral administration of analgesic. Group 2: Flap surgery following non-surgical periodontal therapy after one month with oral administration of Ketorolac 400mg one hour prior to the surgery. Group 3: Flap surgery following non-surgical periodontal therapy after one month with oral administration of 2 mg Melatonin one hour prior to the surgery. VAS and FLACC score along with blood pressure, SPO2 and heart rate. Statistical analysis was done using SPSS software. The intragroup comparisons (control–test drug) demonstrated that melatonin and ketorolac showed positive preemptive effect which compared to the control with mean differences significantly different from zero. However, when melatonin and ketorolac were compared there was no significant difference in postoperative pain among patients. The adoption of a preemptive medication protocol using either melatonin or ketorolac may be considered effective for pain and discomfort prevention during and post open-flap debridement surgeries. Melatonin showed similar effect to gold standard ketorolac in terms of its preemptive analgesic effect additional to having anti-inflammatory effect. Further studies are required to standardize the protocol for using melatonin as preemptive analgesic for dental surgical procedures.
Awareness on passive smoking among Indian adults
Authors: Sivasubramanian N
Published: March 2023

Around one-third of adults worldwide regularly come into contact with passive smoking. In addition to many other health issues, non-smokers who are exposed to passive smoking at home or at work have a 20–30% higher risk of acquiring lung cancer. The current study set out to determine adult smokers' awareness of the hazards of passive smoking as well as the efficacy of an education campaign in raising that awareness. To finish the investigation, a pre-experimental research approach was employed. 60 adults between the ages of 18 and 45 were chosen by non-probability purposive sampling. Results revealed that the mean of pre-test score was 12.33 and mean of post-test score was 21.5. The mean difference was 9.17. The standard deviation of pre-test knowledge score was 2.87 and standard deviation post-test knowledge score was 3.27. The calculated ‘t’ value is 14.80, the DF value was 59 and p value was 1.671. This shows that the teaching program was effective in increasing the awareness of adults regarding effects of passive smoking. Age and education status of the sample were found to have significant association with the level of awareness in pre-test. Teaching programs can be effectively utilized to create awareness among adults regarding adverse effects of passive smoking.
Application of nanoparticles in Dentistry
Authors: Missier Mary Sheloni
Published: March 2023

Nanoparticles(NPs) are of particle sizes lesser than 100nm and are insoluble the field which deal with the handling of these particles is coined as “Nanotechnology” as their particle size is smaller, they can penetrate easily therefore they are applied in various medical fields, drug delivery and in dentistry as they have antimicrobial property, reduces friction, anti-inflammatory and antioxidant property. Many studies have been done to evaluate its application and its cytotoxicity by varying its concentration and various studies have been done to evaluate its physical property. Therefore, it is of interest to describe concepts of nanoparticles, mode of action, tissue reaction and its application in orthodontics.
Molecular docking analysis of calcium channel blockers with ALR2 and RAGE
Authors: Kazmi Samreen
Published: March 2023

A metabolic condition called diabetes mellitus is linked to a number of substantial challenges. Advanced Glycation End Products (AGEs) and Aldose reductase (ALR2) are crucial in the slow development of several secondary complications. Selected calcium channel blockers (CCB’s-1, 4-dihydropyridines) were docked against ALR2 (PDB code: 1Z3N) and RAGE (PDB code: 3CJJ) in the current study. We report that 1, 4-dihydropyridine compounds, particularly Benidipine, bind to the active sites with good efficiency. Thus, 1,4 dihydropyridine derivatives can be considered for further confirmation in drug discovery.
Insights from the molecular docking analysis of GRP78 with natural compound inhibitors in the management of cancers
Authors: Alam Qamre
Published: March 2023

Cancer is regarded as one of the world's most serious health issues. Glucose regulated protein (GRP78) exhibits a vital role in the proliferation, invasion, and metastasis of numerous cancer cells. Based on that, this study screened the 390 natural compounds targeting the GRP78 catalytic site. Among them, corynanthin, toyocamycin, and nanaomycin were found to strongly bind with GRP78 and possess the binding affinities of -8.4, -8.9, and -8.7 kcal/mol, respectively. In addition, these compounds interacted with key residues of GRP78 and have several amino acid residues interaction in common with the cocrystal ligand (ATP). Based on physicochemical parameters and ADME evaluations, these compounds were found to have good drug-like properties. These compounds could be used as possible GRP78 inhibitors in the fight against cancers. Albeit, exhaustive experimental studies would be required to confirm the findings described here.
In-vitro anticancer activity of Rauvolfia tetraphylla extract on mcf-7 breast cancer cell lines
Authors: Sabu Abraham
Published: March 2023

The medicinal herb Rauwolfia tetraphylla is utilized by South Indian tribes to treat various medical ailments, although its cytotoxicity action has not been studied. As a result, the emphasis of the current investigation is on the anticancer activity of Rauvolfia tetraphylla extracts on MCF-7 breast cancer cell lines, as well as their effects on the levels of gene expression for BCl2 and TGF. The study found that the anticancer activity of R. tetraphylla extract demonstrated significant cytotoxic activity against MCF-7 breast cancer cell lines. Because of this, its anticancer effect may be caused by apoptosis, which is caused by DNA breaking and is helped by active phytochemicals like alkaloids, phenols, and flavonoids in the extracts. It also promotes apoptosis by altering Bcl-2 and TGF expression levels. The present study suggests using R. tetraphylla extract as an anticancer agent in traditional medicine.
Molecular docking analysis of Aza compounds with the heme-binding protein from Tannerella Forsythia
Authors: Sathiamurthy Janani
Published: March 2023

The high biological activity and interesting optical properties of the aza compounds is known. Therefore, it is of interest to document the molecular docking analysis data of Aza compounds with the heme-binding protein from an anaerobic, Gram-negative bacterium Tannerella Forsythia. Hence, we report the optimal binding features of Aza compounds with the heme-binding protein from Tannerella Forsythia for further consideration in drug discovery against the pathogen.
Molecular docking analysis of the oral tumor target JAK STAT 3 with oxo-azo compounds
Authors: Karikalan Kaviya
Published: March 2023

It is of interest to identify the JAK STAT 3 signaling inhibitors to abrogate tumorigenesis in oral cancer. Hence, molecular docking was performed with known oxazole compounds (1-5) and the 3D crystal structure of JAK-1 protein from Homo sapiens (PDB ID: 3EYG). The results show that the oxo-azo derivatives showed better interactions within the binding site of proteins. We report that compounds 1, 4 and 5 optimal binding features with JAK STAT 3.
Sleep disorders and work-related stress with oral hygiene among Indian shift workers
Authors: Kumaresan Sathya
Published: March 2023

Construction workers are mostly migrants from isolated villages and are not vigilant about health care measures besides poor language skills. Majority of the population works in shifts across the globe. As a result of poor sleep architecture, excessive sleepiness or insomnia, the construction labourers working in shifts have approximately twice the risk of OSA when compared with those working in the daytime. Likewise, the performance and the productivity of employees in construction sites are impeded by added stress. Therefore, it is of interest to investigate the sleep disorders, work-related stress and its impact on oral hygiene among the construction workers in Chennai. A cross sectional study was conducted among 518 workers in various construction sites at Chennai, South India. The study incorporated Berlin Questionnaire to evaluate disordered breathing during sleep, the Work Ability Index that contains questions concerning work, working ability and health and the Oral Hygiene Index Simplified (Greene and Vermillion, 1964) that was used for recording the oral hygiene status. Pearson correlation between education and OHI-S was statistically significant (r=-0.108). Multiple linear regression analysis revealed that mean WAI score had a positive significant association with work experience (B=0.059, SE=0.030, p=0.05), habits (B=0.032, SE=0.017, p=0.05) and marital status (B=0.135, SE=0.54, p=0.01). In contrast, education (B=-0.0.052, SE=0.023, p=0.02) and work schedule (B=0.022, SE=0.037, p=0.54) were inversely associated with the mean score. Based on the current findings, it is imperative to restore work ability for those with poor work ability thereby enhancing productivity in the migrant workers. As shift work may be extremely detrimental to poor sleep quality, the employers should arrange shift schedules in accordance with sleep physiology. Additionally, dental awareness and interventions are required to improve oral hygiene among migrant workers.
Molecular docking analysis of Indole based diaza-sulphonamides with JAK-3 protein
Authors: Nautiyal Manya
Published: March 2023

JAK-3 gene is a part of an important signalling pathway in oral cancer. Therefore, it is of interest to evaluate the inhibitory properties of new indole based diaza-sulphonamides compounds against JAK3 gene. Molecular docking analysis showed that among the selected compounds (1-9), the compounds 1-4 turned out to be the most potentially capable ones to be used as ant-cancer drugs. Also, they are proved to be non-toxic.
Molecular docking analysis of Indole based oxadiazoles with the H-binding protein from Treponema denticola
Authors: Kumaran Poojitha
Published: March 2023

Treponema denticola is a gram-negative bacteria that is associated with periodontal diseases. Literature derived, six indole based oxadiazole derivatives are docked with the target Factor H binding protein (fHbp) protein. Results show better docking interaction compared to clinically proven drugs and all compounds obey Lipinski’s rule of five. Hence, the compounds were inferred to be potential inhibitors for factor H binding protein of Treponema denticola.
Molecular docking analysis of imidazole quinolines with gingipain R from Porphyromonas gingivalis
Authors: Reddy Reddy
Published: March 2023

Porphyromonas gingivalis is known to produce major virulence factor, Gingipain R that could penetrate the gingivae and cause tissue destruction. In this research we aim to target the gingipain R protein with imidazole quinoline derivatives (1-6) via insilico means. Molecular docking results show, compounds (1-6) have better affinity and amino acid interactions compared to the standard clinically proven drugs used as control group, and they obey Lipinski’s rule of five and can be used as potential drug candidates to inhibit gingipain R.
Molecular docking analysis of thiazo inhibitors with the virulent factor cystalysin from Treponema denticola
Authors: Andrew Serafina
Published: March 2023

Treponema Denticola has a virulent protein called cystalysin, which causes periodontitis. Therefore, it is of interest to design efficient drug that may have fewer side effects than the present clinical drugs, considering most of them are multidrug resistant. The molecular docking analysis show that the selected thiazo derivatives (1-6) show better binding energies and amino acid interactions compared to the clinically proven drugs proving to be potential inhibitors against the protein.
Molecular docking analysis of oxazole compounds with the heme-binding protein from Porphyromonas gingivalis
Authors: Manikandan Pranaw
Published: March 2023

Porphyromonas gingivalis, a peripathogen, has several methods to impede or modify the protective mechanisms of the teeth. Targeting the inhibition of the heme protein will prevent the organism from multiplying and inhibit the virulence mechanism. The literature derived oxazole compounds (1-5) were docked against the protein's active site, and the results show that the selected oxazole derivatives exhibit better interaction compared to clinically proven drugs.
Molecular docking analysis of the tumor protein beta arrestin-1 with oxadiazole compounds
Authors: Sharma Vipra
Published: March 2023

Beta arrestins are a family of adaptor proteins that help in the regulation of signaling and trafficking of various G protein coupled receptors (GPCRs). Six oxadiazole derivatives taken from literature are analyzed for anti-cancer properties. The toxicity profiles of all the drugs were similar to Tamoxifen used as control. Data shows that compounds 2, 4, and 6 exhibited comparably significant molecular interactions with the cancerous protein for further consideration.
Platelet-rich fibrin and titanium-prepared platelet-rich fibrin in endoperio lesion management
Authors: Makkad Ramanpal Singh
Published: March 2023

Endo-perio lesions involve a variety of therapy choices that will lead to the best possible elimination of infection. Various therapy approaches have been investigated for curing of patients affected by endo-perio abnormalities. One of the second-generation platelet derivatives is plasma enriched with platelet (PRP).They may aid in the healing of wounds. Enhanced with platelets cells and several growth factors, platelet-rich fibrin (PRF) promotes repair and healing and regeneration of tissue at the periapical area. Platelet cell and leukocyte cell enriched fibrin, prepared in conjunction with titanium (T-PRF), is analogous to fibrin made using the traditional PRF process.The current study was undertaken to compare PRF against T-PRF in the therapy of endo-perio abnormalities using the basic information that was available.280 patients of all sexes between the ages of 18 years and 58 years make up the study's participants. They were divided into two categories. In category I study participants PRF was employed to fill the defect created due to pathology and in category II patients, a T-PRF was used, accompanied by suturing. The one walled, two walled, and three-wall walled infrabony abnormalities were quantified on the digital images acquired using the grid. After three months and six months, the probing periodontal pocket depth in mm and level of attachment (RAL) in mm were measured. In category one, mean change at 3 months was 3.21mm accounting for 33.79% change in PPD. On the other hand mean change at 6 months was 3.61mm accounting for 43.79% change in PPD. When there was evaluation in study participants in category two then it was observed that mean change at 3 months was 2.02mm accounting for 34.79% change in PPD. On the other hand mean change at 6 months was 3.62 mm accounting for 44.79% change in PPD. There was reduction of depth of periodontal pocket at both 3 months follow up and 6 months follow in both categories; however there was no statistical significant variation observed between the two categories regarding decrease in the depth of periodontal pocket on analysis of intergroup variations. It was concluded that there was increase in periodontal attachment and decrease in depth of periodontal pocket in both PRF and T-PRF however there was no statistical substantial variation observed between the two categories regarding increase in the attachment level or decrease in depth of periodontal when intergroup variations between PRF and T-PRF were considered.
Bilateral orthodontic extractions using physics versus conventional forceps among Indian patients
Authors: Sangra Vidhi
Published: March 2023

It is of interest to assess whether or not physics forceps are superior to traditional forceps for the extraction of premolar teeth in orthodontic procedures. Tooth and buccal bone fractures, as well as extraction time, lacerated gingiva, postoperative discomfort, and infection, were all measured in this research of both types of forceps extraction. Twenty individuals who need orthodontic extraction on both jaws were enrolled in the research. One arch's premolars were removed in two appointments, the first using Physics forceps and the second using conventional ones. The subsequent assignment included extraction from the obverse arch. Intraoperative evaluations included assessments of factors such as tooth and buccal bone fractures, surgical time, and gingival lacerations; postoperative assessments of pain and infection were conducted on days 1, 3, and 7. With physics forceps, the average time to remove a patient's mandible was 86.55 seconds, whereas traditional forceps required just 35.70 seconds. Using traditional forceps, the average pain score was 0.865 on day one after surgery, but with physics forceps, it was 3.30. The use of physics forceps resulted in one buccal bone fracture out of twenty premolar extractions. That so, no meaningful statistical change was seen. There was no tooth damage or post-operative infection with either set of forceps, it was found. Each forceps caused a Grade I laceration to the gingiva. The average time required removing a maxillary using physics forceps was 224.05 seconds, whereas the time required doing it with conventional forceps was 141.50 seconds. On a Visual Analogue Scale (VAS), the average first-day pain after surgery using physics forceps was 4.90, whereas using traditional forceps resulted in just 3.15. The difference between using physics forceps and regular forceps was statistically significant by the third postoperative day (2.05 vs 0.75). There was a statistically insignificant increase in the occurrence of buccal bone fracture and tooth fracture while using physics forceps. Both forceps and scissors caused just grade I lacerations, and there was no postoperative infection. These findings suggest that the use of physics forceps, as opposed to conventional forceps, may significantly lengthen the time required to remove orthodontic premolars on both sides of the mouth. Non-significant results were also found for additional criteria such as buccal bone fracture, tooth fracture, gingival laceration, and post-operative discomfort. When it comes to orthodontic premolar extraction, this research found that traditional forceps performed better than modern forceps across a range of measures, including intraoperative time and postoperative discomfort.
Creative Industries as Platform for Citizen Participation in Cultural Transformation of Minsk Urban Space
Authors: Krivolap Alexei
Published: March 2023

Creative industries do not make revolutions in city planning but transform the ways of thinking about and practicing urban space development. In the context of Minsk, Belarus, creative industries are a part of the contemporary urban infrastructure transformation that is reestablishing the former Soviet urban space. The aim of this article is to document and analyze the ways that creative industries turn the urban spaces of Minsk into participatory platforms for cultural transformations. The development of these creative industries in Belarus has played a crucial role in transforming urban spaces into new inclusive cities. The distinctive feature of Belarusian creative industries is their embeddedness in the spaces of Soviet cities. Empirically, this text is based on the findings of a qualitative empirical study in the framework of grounded theory. The research seeks to understand the self-narrative and self-identification of the new creative class in Minsk (spring and summer 2018). The respondents were people who are involved in the process of developing creative industries in Belarus.
Shift in Balance: UK Perspective on Democratic Deficit Addressed by Participatory Turn and Gamification
Authors: Duke Benjamin
Published: March 2023

This paper provides a conceptual theoretical review of participatory turn and gamification from a United Kingdom (UK) perspective. Democratic deficit is a perennial problem in urban-planning systems due to the number of causal factors. Participatory practices and gamification are two instruments that can be used to help alleviate low democratic responsiveness. The paper articulates how there are different ways of knowing and assessing community priorities and values � people need increased consciousness and self-confidence to participate. The UK case studies that are discussed have made a significant contribution by providing useful insights regarding the benefits and limitations of participatory practices and gamification. For example, �Participology� and �Geogopoly� have clear participatory gamification benefits even though they are unable to include decision-maker accountability or recreate real-life power relationships. This paper posits that the use of participatory practices and/or gamification as policy levers (specifically in UK urban-planning processes) will herald a shift in the balance of power.
Platformization of Politics in Non-democracies: Spaces of Participatory Experiments In Belarus in 2020S
Authors: Liubimau Siarhei
Published: March 2023

This paper�s focus is on the innovations in the urban public political agenda that are due to the interplay between participatory digital platforms, the socio-economic paths of specific urban environments, and long-term policy orientations on the national and urban levels. The context of the 2020 presidential elections in Belarus and the resulting boom of participation in the local and national political agendas is taken here as a particular configuration of the mentioned interplay and its outcomes. The first part of the paper focuses on the role of digital platforms in the studied boom of participation in 2020, the second documents the urban policy developments in Belarus during the period of 2015�2020, and the third reflects on the compatibility of the Belarusian case with wider discussions on the political impact that the spread of digital platforms has on urbanism. It is argued that the repressive state, the gradual marketization of urban development and the accompanying strengthening of urban dwellers� economic autonomy, and the proliferation of commercial digital platforms and civic tech are the factors that have defined the studied politicization and the boom of participation in Belarus. The examined case shows the contours of emerging politics in non-democracies under conditions of ubiquitous digitalization and the pressure on the state�s redistributive capacities.
Etyczne uzasadnienie zarz�dzania danymi medycznymi w perspektywie dzia�a� rozwojowych Unii Europejskiej
Authors: Ruci�ski Kuba Piotr , Lewandowski Piotr
Published: March 2023

Nieustannie rozwijaj�ce si� spo�ecze�stwo europejskie aktywnie mierzy si� z problemami etycznymi, dotykaj�cymi ka�dej cz�ci �ycia. Tekst ma na celu zaprezentowanie problematyki zarz�dzania danymi medycznymi oraz zaproponowanie uzasadnienia dla tego obszaru dzia�alno�ci badawczo-rozwojowej z perspektywy Unii Europejskiej przy uwzgl�dnieniu istniej�cych ju� warto�ci oraz podej�cia filozoficznego. Na podstawie wybranych koncepcji prezentuj�cych r�ne dziedziny filozofii oraz bioetyki artyku� prezentuje holistyczne i nowoczesne podej�cie do zagadnienia etyki w zarz�dzania danymi. Punktem wyj�cia dla tego typu rozwa�a� sta�a si� teoria umowy spo�ecznej T. Hobbesa, kt�ra omawia powinno�ci cz�owieka wobec spo�ecze�stwa oraz wolno�ci przys�uguj�cych cz�owiekowi. Dyskurs analityczny zosta� wsparty koncepcjami filozoficznymi L. Floridiego oraz A. Dawsona. Te dwa paradygmaty pomagaj� zakre�li� nowoczesne problemy i terminologie, kt�re staraj� si� uchwyci� zmieniaj�ce si� aspekty technologiczne dzisiejszego �wiata.
RS-Based Assessment: Spatial-Temporal Changes in Water Basins of Tar and Havir Lakes
Authors: Afshinfar Afshin , Vahidi Sara , Hatamzadeh Vahid , Nouri Paniz
Published: March 2023

In recent studies several factors such as landslides, volcanoes, glaciers, tectonic factors and karst forms such as flooded pulleys resulting of karsts development cause the formation of lakes in mountainous areas. The mountain lakes of Iran, including Tar and Havir lakes, are mainly formed by landslides. In this research investigation of water basins changes for (Tar and Hoyer lakes) by remote sensing method in the period from 2013 to 2022 have been done. It has been tried to select appropriate Landsat 8 satellite images in terms of cloud cover and image quality from the time when the lakes are full of water. The training and testing data were selected with the same distribution in the whole image to make the classifications more accurate. After estimate kappa coefficient and overall accuracy for all kind of supervised and unsupervised methods, the results obtained from the two classification methods of maximum likelihood and support vector machine with linear kernel from Tar and Havir lakes, the conclusion was that the classification method of support vector machine with linear kernel have better distinguish land and water areas and it is the best method for classifying water basins located in mountainous areas. The amount of water in Tar and Havir lakes had been increased from 2013 to 2017but in 2018, the water area of ​​both lakes decreased significantly, and in 2019, the largest water area for the lakes was observed and calculated. In 2020, there is no big change in the water area of ​​the two lakes, and from 2020 to 2022, the amount of water in the two lakes is decreasing.
Binge drinking and violence in the transition to adulthood
Authors: Savage Joanne , Rossler Michael
Published: March 2023

We analyzed data from the National Longitudinal Study of Adolescent Health (Add Health) to test the hypothesis that binge drinking, rather than frequency of any drinking, would predict violent behavior in the transition from adolescence to adulthood (TAA). In conservative models, accounting for a host of factors relevant to the TAA, we find that binge drinking, but not frequency of drinking, is associated with violent behavior. The models included a control for nonviolent offending, conforming to studies of the “differential etiology of violence” thesis. In addition, we tested whether this association fell away among participants over the age of 21 and found that underage status did not mediate the association between binge drinking and violent behavior.
A Dual‐Drug Nanohybrid System Incorporating Nimodipine and Brain‐Derived Neurotrophic Factor Promotes Retinal Ganglion Cells Survival
Authors: Shen Yuening , Zhang Zhutian , Wang Guanhong , Huang Chang , Quan Yadan , Zhang Shenghai , Wu Jihong , Sun Jianguo , Sun Xinghuai
Published: March 2023

Glaucoma, a leading cause of irreversible visual impairments and even blindness, is characterized by elevated intraocular pressure and progressive loss of structure and function of neuronal systems. To effectively protect neuronal systems from damage caused by elevated intraocular pressure, a novel dual‐drug nanohybrid has been developed by incorporating brain‐derived neurotrophic factor (BDNF)‐loaded mesoporous silica nanoparticles (BDNF@MSN) into the thermogel matrix with nimodipine (NMD) (BDNF@MSN‐NMD@Thermogel). The carrier materials (i.e., silica and thermogel) in this nanohybrid do not show any cytotoxicity to human lens epithelial cells and rat retinal precursor cells. This nanohybrid regulates the in vitro release of BDNF and NMD in a sustainable way for weeks. In optic nerve crush rodent models, a single intravitreal injection of BDNF@MSN‐NMD@Thermogel inhibits retinal neuroinflammation, significantly promotes retinal ganglion cells survival and restores visual function for nearly three months. This nanohybrid is thus a promising alternative for effective neuroprotection treatment for neuroinflammation‐related neurodegenerative diseases.
Click chemistry in the design of AIEgens for biosensing and bioimaging
Authors: Giel Marie‐Claire , Hong Yuning
Published: March 2023

The development of rapid, selective, and sensitive fluorescent sensors is essential for visualizing and quantifying biological molecules and processes in vitro, ex vitro, and in vivo, which is important for not only fundamental biological studies but the accurate diagnosis of diseases. The emerging field of activity‐based sensing (ABS), a sensing method that utilizes molecular reactivity for analyte detection possesses many advantages including high specificity, sensitivity and accuracy. The aggregation caused quenching phenomenon which occurs in most conventional fluorophores results in reduced labeling efficiency of the target analytes and low photobleaching resistance, therefore limiting the applications of the ABS strategy. In contrast, aggregation induced emission (AIE) active luminogens (AIEgens) provide exceptional molecular frameworks for ABS. Of the many reaction classes utilized in the AIEgen ABS approach, click chemistry has become increasing popular. In this review, the sensing concepts of the ABS approach with AIEgens and the principles of click chemistry are discussed, followed by a systematic summary of the application of specific click chemistry reactions in AIEgen ABS protocols for the detection of an array of target analytes. Furthermore, the utility of click chemistry in the construction of AIEgens for bioimaging will also be showcased throughout the review.
A gated strategy stabilizes room‐temperature phosphorescence
Authors: Gu Kaizhi , Meng Zhengong , Liu Xing Wang , Wu Yue , Qi Xin , Ren Yiran , Yu Zhen‐Qiang , Tang Ben Zhong
Published: March 2023

Room‐temperature phosphorescence (RTP) of purely organic materials is easily quenched with unexpected purposes because the excited triplet state is extremely susceptible to external stimuli. How to stabilize the RTP property of purely organic luminogens is still challenging and considered as the bottleneck in the further advancement of the bottom‐up approach. Here, we describe a gated strategy that can effectively harness RTP by employing complexation/dissociation with proton. Due to the order‐disorder transition orientation of intermolecular packing, the RTP of organic molecules 2,4,6‐tris(4′‐bromo‐[1,1′‐biphenyl]‐4‐yl)‐1,3,5‐triazine (Br‐TRZ) will easily vanish upon mechanical force. Impressively, by enhancing its intramolecular charge transfer effect, the protonated Br‐TRZ stubbornly possesses an obvious RTP under external grinding, whatever in the ordered or disordered intermolecular arrangement state. Consequently, the “Lock” gate of RTP was achieved in the protonated Br‐TRZ molecule. Combined with theoretical calculation analysis, the enhanced charge transfer effect can narrow the singlet−triplet energy gap significantly, and stabilize the RTP property of triazine derivative sequentially. Furthermore, the locked RTP can be tuned via proton and counterions repeatedly and show excellent reversibility. This gated RTP concept provides an effective strategy for stabilizing the RTP emission of purely organic systems.
Neurologic Manifestations of Long COVID Differ Based on Acute COVID‐19 Severity
Authors: Perez Giraldo Gina S. , Ali Sareen T. , Kang Anthony K. , Patel Tulsi R. , Budhiraja Shreya , Gaelen Jordan I. , Lank Grace K. , Clark Jeffrey R. , Mukherjee Shreya , Singer Tracey , Venkatesh Aditi , Orban Zachary S. , Lim Patrick H. , Jimenez Millenia , Miller Janet , Taylor Carolyn , Szymanski April L , Scarpelli Jessica , Graham Edith L. , Balabanov Roumen D. , Barcelo Bianca E. , Cahan Joshua G. , Ruckman Kaitlyn , Shepard Alan G. , Slutzky Marc W. , LaFaver Kathrin , Kumthekar Priya U. , Shetty Neil K. , Carroll Katherine S. , Ho Sam U. , Lukas Rimas V. , Batra Ayush , Liotta Eric M. , Koralnik Igor J.
Published: March 2023

Objective

To characterize neurologic manifestations in post‐hospitalization Neuro‐PASC (PNP) and non‐hospitalized Neuro‐PASC (NNP) patients.

Methods

Prospective study of the first 100 consecutive PNP and 500 NNP patients evaluated at a Neuro‐COVID‐19 clinic between 5/2020 and 8/2021.

Results

PNP were older than NNP patients (mean 53.9 vs 44.9 y; p < 0.0001) with a higher prevalence of pre‐existing comorbidities. An average 6.8 months from onset, the main neurologic symptoms were “brain fog” (81.2%), headache (70.3%), and dizziness (49.5%) with only anosmia, dysgeusia and myalgias being more frequent in the NNP compared to the PNP group (59 vs 39%, 57.6 vs 39% and 50.4 vs 33%, all p < 0.003). Moreover, 85.8% of patients experienced fatigue. PNP more frequently had an abnormal neurologic exam than NNP patients (62.2 vs 37%, p < 0.0001). Both groups had impaired quality of life in cognitive, fatigue, sleep, anxiety, and depression domains. PNP patients performed worse on processing speed, attention, and working memory tasks than NNP patients (T‐score 41.5 vs 55, 42.5 vs 47 and 45.5 vs 49, all p < 0.001) and a US normative population. NNP patients had lower results in attention task only. Subjective impression of cognitive ability correlated with cognitive test results in NNP but not in PNP patients.

Interpretation

PNP and NNP patients both experience persistent neurologic symptoms affecting their quality of life. However, they harbor significant differences in demographics, comorbidities, neurologic symptoms and findings, as well as pattern of cognitive dysfunction. Such differences suggest distinct etiologies of Neuro‐PASC in these populations warranting targeted interventions. ANN NEUROL 2023;94:146–159
Astrocyte‐Derived Exosomes Contribute to Pathologies of Neuromyelitis Optica Spectrum Disorder in Rodent Model
Authors: Xie Yi , Chen Bo , Wang Qiong , Chen Xuejiao , Lai Wenwen , Xu Yaping , Deng Saiyue , Yu Zhiyuan , Xie Minjie , Bu Bitao , Mou Dapeng , Yi Chenju , Ding Fengfei , Wang Wei
Published: March 2023

Objective

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease that leads to severe disability. A large proportion of NMOSD patients are seropositive for aquaporin‐4 autoantibodies (AQP4‐IgG, named as NMO‐IgG) targeting AQP4, which is selectively expressed on astrocytes in the central nervous system. This study tests the hypothesis that in response to NMO‐IgG, the pathogenic astrocyte‐derived exosomes are released and injure the neighboring cells.

Methods

IgG purified from serum of either NMOSD patients or healthy controls was used to generate astrocyte‐derived exosomes (AST‐ExosNMO vs AST‐ExosCON) in cultured rat astrocytes. The exosomes were respectively delivered to cultured rat oligodendrocytes in vitro, tissue culture of rat optic nerve ex vivo, and rat optic nerve in vivo to evaluate the pathogenic roles of AST‐ExosNMO. The microRNA (miRNA) sequencing of AST‐Exos and verification were performed to identify the key pathogenic miRNA. The custom‐designed adeno‐associated virus (AAV) antagonizing the key miRNA was evaluated for its therapeutic effects in vivo. Moreover, the serum levels of the key exosomal miRNA were measured between NMOSD patients and healthy controls.

Results

AST‐ExosNMO led to notable demyelination in both cultured oligodendrocytes and optic nerve tissue. Exosomal miR‐129‐2‐3p was identified as the key miRNA mediating the demyelinating pathogenesis via downstream target gene SMAD3. AAV antagonizing miR‐129‐2‐3p protected against demyelination in an NMOSD rodent model. The serum exosomal miR‐129‐2‐3p level was significantly elevated in NMOSD patients and correlated with disease severity.

Interpretation

Astrocytes targeted by NMO‐IgG release pathogenic exosomes that could potentially be used as therapeutic targets or disease monitoring biomarkers in NMOSD. ANN NEUROL 2023;94:163–181
Network Architecture of Verticality Processing in the Human Thalamus
Authors: Conrad Julian , Baier Bernhard , Eberle Laurenz , Ruehl Ria Maxine , Boegle Rainer , Zwergal Andreas , Dieterich Marianne
Published: March 2023

Objective

Thalamic dysfunction in lesions or neurodegeneration may alter verticality perception and lead to postural imbalance and falls. The aim of the current study was to delineate the structural and functional connectivity network architecture of the vestibular representations in the thalamus by multimodal magnetic resonance imaging.

Methods

Seventy‐four patients with acute unilateral isolated thalamic infarcts were studied prospectively with emphasis on the perception of verticality (tilts of the subjective visual vertical [SVV]). We used multivariate lesion–symptom mapping based on support‐vector regression to determine the thalamic nuclei associated with ipsiversive and contraversive tilts of the SVV. The lesion maps were used to evaluate the white matter disconnection and whole brain functional connectivity in healthy subjects.

Results

Contraversive SVV tilts were associated with lesions of the ventral posterior lateral/medial, ventral lateral, medial pulvinar, and medial central/parafascicular nuclei. Clusters associated with ipsiversive tilts were located inferiorly (ventral posterior inferior nucleus) and laterally (ventral lateral, ventral posterior lateral, and reticular nucleus) to these areas. Distinct ascending vestibular brainstem pathways terminated in the subnuclei for ipsi‐ or contraversive verticality processing. The functional connectivity analysis showed specific patterns of cortical connections with the somatomotor network for lesions with contraversive tilts, and with the core multisensory vestibular representations (areas Ri, OP2‐3, Ig, 3av, 2v) for lesions with ipsiversive tilts.

Interpretation

The functional specialization may allow both a stable representation of verticality for sensorimotor integration and flexible adaption to sudden changes in the environment. A targeted modulation of this circuitry could be a novel therapeutic strategy for higher level balance disorders of thalamocortical origin. ANN NEUROL 2023;94:133–145
Cell damage evaluation by intelligent imaging flow cytometry
Authors: Yao Yifan , He Li , Mei Liye , Weng Yueyun , Huang Jin , Wei Shubin , Li Rubing , Tian Sheng , Liu Pan , Ruan Xiaolan , Wang Du , Zhou Fuling , Lei Cheng
Published: March 2023

Essential thrombocythemia (ET) is an uncommon situation in which the body produces too many platelets. This can cause blood clots anywhere in the body and results in various symptoms and even strokes or heart attacks. Removing excessive platelets using acoustofluidic methods receives extensive attention due to their high efficiency and high yield. While the damage to the remaining cells, such as erythrocytes and leukocytes is yet evaluated. Existing cell damage evaluation methods usually require cell staining, which are time‐consuming and labor‐intensive. In this paper, we investigate cell damage by optical time‐stretch (OTS) imaging flow cytometry with high throughput and in a label‐free manner. Specifically, we first image the erythrocytes and leukocytes sorted by acoustofluidic sorting chip with different acoustic wave powers and flowing speed using OTS imaging flow cytometry at a flowing speed up to 1 m/s. Then, we employ machine learning algorithms to extract biophysical phenotypic features from the cellular images, as well as to cluster and identify images. The results show that both the errors of the biophysical phenotypic features and the proportion of abnormal cells are within 10% in the undamaged cell groups, while the errors are much greater than 10% in the damaged cell groups, indicating that acoustofluidic sorting causes little damage to the cells within the appropriate acoustic power, agreeing well with clinical assays. Our method provides a novel approach for high‐throughput and label‐free cell damage evaluation in scientific research and clinical settings.
Policy implementation barriers in climate change adaptation: The case of Pakistan
Authors: Masud Shafaq , Khan Ahmad
Published: March 2023

This article focuses on the policy implementation barriers that result in poor adaptation and enhanced risk of exposure to extreme vulnerabilities, based on experiences in Pakistan. A number of policy implementation barriers are identified including: (i) Whether policy development is seen as a closed or open consultation process, (ii) Whether policy is seen as a generic document or an instrument for specific actions, and (iii) Whether policy administration is seen as a central or devolved process. As a case study, Pakistan's national climate change policy was considered. Pakistan is the eighth most climate change impacted country in the world. The results conclude that a prevalent top‐down frame of management, centred‐around federalism, has created vacuums for misinterpretation, poor understanding amongst policy implementers and false expectations of policy goals. A critical aspect of this disconnect is the lack of inclusivity of critical stakeholder groups in the policy design and development stages thus creating various barriers resulting in mistrust between different governing entities and vice versa. The study also highlights the nature of this problem and recommends a closer examination of the prerequisites of engagement in climate decision‐making for better understanding and implementation of adaptation practices in de‐centralised governance.
Two volcanic tsunami events caused by trapdoor faulting at a submerged caldera near Curtis and Cheeseman Islands in the Kermadec Arc
Authors: Sandanbata Osamu , Watada Shingo , Satake Kenji , Kanamori Hiroo , Rivera Luis
Published: March 2023

Two submarine earthquakes (M 5.8)
occurred near volcanic islands, Curtis and Cheeseman, in the Kermadec
Arc in 2009 and 2017. Following both earthquakes, similar tsunamis with
wave heights of about a meter, larger than expected from their moderate
seismic magnitudes, were observed by coastal tide gauges. We investigate
the source mechanism for both earthquakes by analyzing tsunami and
seismic data of the 2017 event. Tsunami waveform analysis indicates that
the earthquake uplifted a submerged caldera around the islands. Combined
analysis of tsunami and seismic data suggests that trapdoor
faulting, or sudden intra-caldera fault slip interacted with magma
reservoir deformation, occurred due to magma overpressure, possibly in
association with caldera resurgence. The earthquake
scaling relationship for trapdoor faulting events at three calderas
deviates from that for regular earthquakes, possibly due to the
fault-reservoir interaction in calderas.
Influence of energy storage system in nanogrid under dynamic conditions with frequency‐based current controller for battery storage
Authors: Soni Yuvraj Praveen , Fernandez Eugene
Published: March 2023

Maintaining a stable voltage level at the DC bus is crucial to safeguard equipment, ensure a consistent power supply, and enhance system efficiency. A combination of battery storage and photovoltaic (PV) systems is often employed to maintain an equilibrium between energy supply and demand and keep the DC bus voltage within optimal levels. Nonetheless, frequent and rapid charging and discharging of battery storage in dynamic conditions can negatively impact its lifespan. To address this issue, this study utilizes the application of a frequency‐based current controller in battery storage that facilitates smooth charging and discharging operations in transient conditions. The study evaluates the performance of a grid‐tied PV‐based nanogrid (GT‐PVN) system with three distinct configurations: (a) PV system without storage, (b) PV system with battery storage, and (c) PV system with hybrid energy storage system (HESS) under varying dynamic load and irradiance conditions. The results show that the transient performance on DC bus voltage with battery integration is efficiently improved by 0.3%‐0.5% under dynamic irradiance conditions and 0.5%‐1.17% under dynamic load conditions. Further, with HESS installation, the DC bus voltage transients are improved by 0.85%‐1.25% under dynamic irradiance conditions and 0.5%‐1.5% under dynamic load conditions. Moreover, energy storage technology implementation has the potential to decrease energy procurement from the grid by up to 80%. These findings highlight the potential of energy storage technology in mitigating the intermittency and dynamic operational challenges faced by PV systems.