bluuebunny/crossref_metadata_2025 huggingface dataset:
Ayurveda Concept of Medoroga with Special Reference to Obesity and Related Complication and their Medical Management
Authors: Ghanawat Prasad Navanath , Mane Prakash , Nibe Pallavi Lahanu , Mirgane Ravindra
Published: August 2021

Obesity or medoroga is the only disease that is gaining more and more attention at the global level. This disease is prevalent in developing as well as in developed countries, in both sexes, across all ages and socioeconomic groups. Obesity is one of the prices we have to pay for rapid urbanization and a sedentary lifestyle. Obesity has been described in Ayurveda texts as medoroga or Sthaulya. Acharya Charaka has described eight varieties of impediments known as ashta nindita Purusha. Ati Sthaulya comprises one of them. Obesity is the risk factor for many diseases like diabetes, CVA, hypertension, etc. It is difficult to prevent and treat lifestyle diseases like obesity with the modern system of medicine alone. Ayurvedic science has great potential in preventing and treating lifestyle disorders like obesity. The presenter's view deals with aetiopathogenesis, symptomatology prevention, and management of Sthaulya as given in the Ayurveda classics.
Etiology and Management of Hypoventilation Syndromes
Authors: Hussein Mohammed Salah , Abdulhaq Monera Abdulrhman Mohammed , A Albadi Abdullah Anwar , Alsalim Morteda Jasim , Alghamdi Abdulrahman Hafidh A. , Alzidany Montadher Mahfoudh A. , Aljarba Noor Khalid Abdulrazaq , M Alqurashi, Qays Ahmad , Alsinaideh Rakan fahad , Alanazi Tariq Fayadh , Alqahtani Mohammed Mehthel , Albrkheel Abdulrhman Abdulaziz , Alkhodairy Salman Fahad
Published: August 2021

A number of diseases affecting central ventilation, breathing mechanics or both, characterize hypoventilation syndromes. The incidence of hypoventilation syndromes varies according to the underlying reason. The hypoventilation syndrome's clinical symptoms are generally vague and are in most cases due to the underlying clinical condition. More individuals develop hypercapnia and hypoxemia as hypoventilation continues to worsen. Therefore, clinical indications of hypoxemia such as cyanosis, and evidence of hypercapnia may also be present. Regardless of the etiology, successful hypoventilation therapy focuses on the underlying illness and noninvasive ventilation. Treatment for these diseases includes integrated main disorder treatment and, increasingly, non-invasive positive pressure breathing. In this paper, we overview current evidence regarding different etiologies and management of hypoventilation syndromes. Data was collected during the period of 6 months searching Pubmed, EPISCO, Web of science, Google scholar databases to include papers with relative topics.
Therapeutic Effect of Curcumin on Scanning Electron Microscopy of Rat Adrenal Gland in Experimental Fluorosis
Authors: Shashi A. , Tikka Manisha
Published: August 2021

Aim: The present study was designed to investigate the therapeutic role of Curcumin against fluoride induced toxicity on adrenal gland of rats by using scanning electron microscopy (SEM).

Methodology: Wistar albino rats were divided randomly into six groups The group I was administered with 1 ml of deionized water/kg b.w./day orally for 40 days. The Groups II and III were given 300 and 600 mg of NaF/kg b.w./day for the same period, respectively. The group IV was given 200 mg/kg b.w. of Curcumin for 20 days. The Groups V and VI were treated with 300 and 600 mg of NaF/kg b.w./day for 40 days respectively were post-treated with 200 mg of Curcumin for next 20 days. The animals were excised and adrenal tissue was taken out and processed for SEM.

Results: The results revealed that rats exposed to 300 mg/kg b.w./day of NaF showed rough edges, numerous microvilli and damaged surface with crystal depositions. Also, numerous granules were distributed all over the surface. The rats treated with 600 mg/kg b.w./day of NaF showed decellularized adrenal tissue along with network of collagen fibres. Moreover, adrenal gland surface displayed abrasions and distorted cuboidal cells. The filopodia were prominent on the surface and wall of cavity possessed rough outline. After post-treatment with Curcumin, fluoridated adrenal gland of rats showed normal structure, reappearance of cuboidal cells on the surface as well as less number of microvilli and filopodia.

Conclusion: The post-treatment with Curcumin possess therapeutic potential against NaF induced toxicity in adrenal gland of rats.
Association of Vitamin D Receptor Gene Polymorphism with Type 2 Diabetes in the Northern Region of Saudi Arabian Population
Authors: Alharbi Ahmed , Alam Md Jahoor , Saeed Mohd
Published: August 2021

Background: Vitamin D deficiency and vitamin D receptor (VDR) gene polymorphisms are associated with type 2 diabetes mellitus (T2DM), However, its association with type 2 diabetes mellitus) is controversial and has not been established in different ethnic populations. Therefore, we aimed to evaluate the possible association between VDR gene polymorphisms (Fok1, Bsm1, and Taq1and Apa1) and T2DM patients in Saudi Arabia.

Methods: 100 patients with T2DM and 100 healthy age-matched control subjects were enrolled. Fasting blood glucose, lipids profile and HbA1c were measured by autoanalyzer. The circulatory level of 25 hydroxyvitamin D [25(OH)D] was measured by immunochemiluminance. VDR gene polymorphisms detection has been done by polymerase chain reaction through restriction fragment length polymorphism (PCR-RFLP) method.

Results: Our study has shown lower levels of 25(OH) D in patients with T2DM (in comparison with control subjects (44.65 ± 7.19), p < 0.00. There were statistically significant differences between patients with type 2 diabetes and controls regarding the distribution of FokI and Taq1 genotypes and alleles (p<0.004 and p<0.04) and nonsignificant differences regarding Bsm1genotpes and allele.

Conclusions: Vitamin D deficiency is prevalent in T2DM patients in Saudi Arabia. An association was found between VDR FokI and Taq1 gene polymorphism and susceptibility to T2DM in Saudi Arabian patients.
Japanese Encephalitis with Global Aphasia- A Case Report
Authors: Rodge Hina Y. , Maurya Archana
Published: August 2021

Introduction: Japanese Encephalitis (JE) is a brain infection caused by the Japanese Virus of Encephalitis (JEV).JE is also known as Mosquito-Borne Encephalitis, Summer Encephalitis and Brain Fever etc. Global aphasia is caused by a number of factors, one of which is JE.

Presentation of Case: A 15 years old male child was brought to Acharya Vinoba Bhave Rural Hospital, Sawangi (Meghe), Wardha, Maharashtra, India on date 22/08/2019 with complaints of fever since 7 days with 2 episodes of seizures with loss of consciousness for approximately 20 hours and the patient was unable to speak after becoming conscious. On examination, the patient had a fever, was lethargic and appeared depressed, unable to speak, and experienced pain when moving his hands. The patient had a complete blood count, which revealed that his haemoglobin percent, total red blood count, were all low, while his RDW and granulocytes were high. RBCs are predominantly normocytic Normochromic RBCs with mild anisopoikilocytosis, with a few microcytic RBCs, pencil cells, and tear drop cells visible on a peripheral smear as well as platelets were adequate, and no Hemiparasite was found. CSF analysis, CT scan of the brain, an MRI of the brain, and a blood test for P. Falciparum were all performed for diagnostic purposes. The patient was diagnosed as Japanese Encephalitis with Global Aphasia after comprehensive examinations. He was treated Tab. Cefexime, Tab. Levetiracetam, Tab. Phenytoin, Tab. Paracetamol, and Tab. Emset, as well as nursing care was provided based on his needs.

Conclusion: Patient showed spontaneous recovery.
Assessment of Auto-rickshaw Drivers Knowledge Regarding the Effects of Air Pollution on Health and Its Prevention
Authors: Dhanvijay Roshani , Pohekar Savita
Published: August 2021

Background: Air pollution is the major environmental pollution that contains different types of gases, dust particles, small molecules, etc. Air pollution is mainly caused by smoke or other harmful gases, such as oxides of carbon, sulfur, and nitrogen. Auto-rickshaw drivers are not only affected by air pollution, they are exposed to climatic changes, and. poor road conditions. They are exposed to air pollution, dust, infected droplets, job insecurity, noise pollution and vibration, business demands, damage to their vehicles, and, schedule-related pressure. Drivers also have the responsibility of their passengers and pedestrians- ‘lives and other vehicles. The objective of the study is to analyze knowledge among auto-rickshaw drivers regarding the health effects of air pollution and its prevention.

Methods: An observational research methodology, a cross-sectional research design was used to perform this analysis. Probability purposive sampling technique was used to collect data from auto-rickshaw drivers based on the health effects of air pollution and its prevention utilizing structured questionnaires. The sample attributes have been defined by frequency, percentage, after data collection. The Chi-square test was also used to figure out the correlation between knowledge and specified demographic variables.

Results: The findings show that 1.67% of auto-rickshaw drivers had an average level of knowledge score, 38.33% of them were having good and 60 % of them were having an excellent level of knowledge score and none of them were found to have a very poor level of knowledge. The minimum knowledge score was 7 and the maximum knowledge score was 14. Hence it indicates that auto-rickshaw drivers have good knowledge about the effect of air pollution and their prevention.

Conclusions: The study shows that the auto-rickshaw drivers having good knowledge about air pollution to the management of respiratory diseases and along with their complications as well as to take the required measures to avoid respiratory complications.
Evaluation and Management of Septic Arthritis in Emergency Department “Narrative Review”
Authors: Alzahrani Abdulwahab Ahmed , Alluqmani Abdullah Habib H. , Althaqafi Mosab Abdullah , Alhamoud Ahmad Abdulsamad , Kuraydim Faisal Mousa , Alothaimeen Shatha Yahya , Mohammedsaleh Bashaer , Zogeeli Afnan Ahmed Hamod , Muslim Duaa Abdulkadir Al , Nouruldeen Rawan Ismail , Alqahtani Maha Abdullah , Aljuhani Bassam Ibrahim
Published: August 2021

Septic arthritis (SA) is a secondary infective disease due to joints inflammation. It often appears with mono- or oligoarticular acute arthritis that frequently leads to an emergency department (ED) visit with need for prolonged hospitalization. SA is an orthopedic emergency that can threaten both life and limb due to its potential rapid destruction of the joint with fulminant sepsis, causing significant disability within hours to days. Delayed or poor treatment of septic arthritis can lead to irreversible joint damage with consequent disability in addition there to significant mortality rate. Management includes early detection and treatment with antibiotics, joint aspiration, and consultation for orthopedic surgery as potential operative management. This review aims to summarize current evidence regarding evaluation and management of septic arthritis in emergency department, and to highlight the difficulties of diagnosing and managing SA that face the healthcare providers to help overcome those difficulties and to recommend further studies to be done regarding those problems and their solutions.
Structural, Electronic and Optical Properties of Stanene Doped Beryllium: A First Principle Study
Authors: Taura L. S. , Abdulmalik Isah , Gidado A. S. , Lawal Abdullahi
Published: August 2021

Stanene is a 2D hexagonal layer of tin with exceptional electronic and optical properties. However, the semiconductor applications of stanene are limited due to its zero band-gap. However, doping stanene could lead to a band gap opening, which could be a promising material for electronic and optical applications. In this work, optimized structure, electronic band structure, real and imaginary parts of the frequency-dependent dielectric function, electron loss function, and refractive index of stanene substitutionally doped with alkaline earth metal (beryllium) were analyzed using density functional theory (DFT) calculations as implemented in the quantum espresso and yambo suites. A pure stanene has a zero band gap energy, but with the inclusion of spin-orbit coupling in the electronic calculation of pure stanene, the band-gap is observed to open up by 0.1eV. Doping stanene with beryllium opens the band-gap and shifts the Dirac cone from the Fermi level, the band gap opens by 0.25eV, 0.55eV, and 0.8eV when the concentration of Beryllium is 12.5%, 25%, and 37.5% respectively. The Dirac cone vanished when the concentration of the dopant was increased to 50%.  The Fermi level is shifted towards the valence band edge indicating a p-type material. The material absorption shows that SnBe absorption ranges in the visible to the ultraviolet region, The refractive index in stanene doped beryllium (SnBe) was found to be higher than that of pristine stanene, the highest refractive index was 9.2 at SnBe25%. In a nutshell, the results indicate that stanene can be a good material for electronic and optical applications if doped with beryllium.
Hybrid Dielectric Films of Inkjet‐Printable Core–Shell Nanoparticles
Authors: Buchheit Roman , Kuttich Björn , González‐García Lola , Kraus Tobias
Published: August 2021

A new type of hybrid core–shell nanoparticle dielectric that is suitable for inkjet printing is introduced. Gold cores (dcore ≈ 4.5 nm diameter) are covalently grafted with thiol‐terminated polystyrene (Mn = 11000 Da and Mn = 5000 Da) and used as inks to spin‐coat and inkjet‐print dielectric films. The dielectric layers have metal volume fractions of 5 to 21 vol% with either random or face‐centered‐cubic structures depending on the polymer length and grafting density. Films with 21 vol% metal have dielectric constants of 50@1 Hz. Structural and electrical characterization using transmission electron microscopy, small‐angle X‐ray scattering, and impedance spectroscopy indicates that classical random capacitor–resistor network models partially describe this hybrid material but fail at high metal fractions, where the covalently attached shell prevents percolation and ensures high dielectric constants without the risk of dielectric breakdown. A comparison of disordered to ordered films indicates that the network structure affects dielectric properties less than the metal content. The applicability of the new dielectric material is demonstrated by formulating inkjet inks and printing devices. An inkjet‐printed capacitor with an area of 0.79 mm2 and a 17 nm thick dielectric had a capacitance of .
On‐Skin Stimulation Devices for Haptic Feedback and Human–Machine Interfaces
Authors: Guo Wei , Hu Yijia , Yin Zhouping , Wu Hao
Published: August 2021

On‐skin electronics have been widely used in fields, such as wearable healthcare and human–machine interfaces due to their excellent performances and wearable comfort. Among them, on‐skin sensors for collecting signals have been greatly developed, while the stimulators that provide tactile feedback are difficult to achieve in terms of flexibility and stretchability due to their rather complicated structures. Achieving on‐skin stimulators with superior performances and outstanding wearability requires major advances in materials, fabrication, and structure design. The on‐skin stimulator needs to be soft with a lightweight and thin structure so that it can be laminated onto the skin with conformal contact for accurate feedback. Three stimulation modes, namely electrotactile, thermal, mechanotactile, and vibrotactile stimulation, are investigated. Among them, electrotactile stimulation is the characteristics of high resolution and quick response. Thermal stimulation can provide a unique heat sensation without crosstalk with other stimuli. Mechanotactile and vibrotactile stimulation can bring comfortable feedback to skin, showing great potential in wearable applications. This paper summarizes the working principles, materials, structures, and applications of these on‐skin stimulators, and compares their advantages with conventional rigid devices. At the end of this paper, the challenging issues and future prospects in this field are discussed.
Tuning the Elasticity of Polymersomes for Brain Tumor Targeting
Authors: Zheng Meng , Du Qiuli , Wang Xin , Zhou Yuan , Li Jia , Xia Xue , Lu Yiqing , Yin Jinlong , Zou Yan , Park Jong Bae , Shi Bingyang
Published: August 2021

Nanoformulations show great potential for delivering drugs to treat brain tumors. However, how the mechanical properties of nanoformulations affect their ultimate brain destination is still unknown. Here, a library of membrane‐crosslinked polymersomes with different elasticity are synthesized to investigate their ability to effectively target brain tumors. Crosslinked polymersomes with identical particle size, zeta potential and shape are assessed, but their elasticity is varied depending on the rigidity of incorporated crosslinkers. Benzyl and oxyethylene containing crosslinkers demonstrate higher and lower Young's modulus, respectively. Interestingly, stiff polymersomes exert superior brain tumor cell uptake, excellent in vitro blood brain barrier (BBB) and tumor penetration but relatively shorter blood circulation time than their soft counterparts. These results together affect the in vivo performance for which rigid polymersomes exerting higher brain tumor accumulation in an orthotopic glioblastoma (GBM) tumor model. The results demonstrate the crucial role of nanoformulation elasticity for brain‐tumor targeting and will be useful for the design of future brain targeting drug delivery systems for the treatment of brain disease.
Application of Resistive Random Access Memory in Hardware Security: A Review
Authors: Rajendran Gokulnath , Banerjee Writam , Chattopadhyay Anupam , Aly Mohamed M. Sabry
Published: August 2021

Nowadays, advancements in the design of trusted system environments are relying on security provided by hardware‐based primitives, while replacing resource‐hungry software security measures. Emerging nonvolatile memory devices are promising candidates to provide the required hardware security functionalities at very low area‐energy‐runtime budget. Resistive random access memory (RRAM) offers high‐density integration with outstanding performance among the state‐of‐the‐art nonvolatile memory devices. The RRAM device technology is currently getting significant attention from both academia and industry for constructing beyond Von Neumann architectures. This technology's strength is its scalable two‐terminal structure, the availability of wide range of functional materials, and multi‐bit storage capability. The fluctuations in switching resistances, random telegraph noise, and sneak path current are detrimental characteristics of RRAM integrations for storage and in‐memory computing applications, and more research focuses on alleviating these effects. Interestingly, these characteristics make them suitable for designing security hardware. In recent times, there has been significant progress in the design and analysis of RRAM‐based security primitives such as, Physical Unclonable Function, true random number generator, and hash function. This review discusses the detailed developments in RRAM security and presents the demanded security requirement and available opportunities to be explored.
Active Learning in Bayesian Neural Networks for Bandgap Predictions of Novel Van der Waals Heterostructures
Authors: Fronzi Marco , Isayev Olexandr , Winkler David A. , Shapter Joseph G. , Ellis Amanda V. , Sherrell Peter C. , Shepelin Nick A. , Corletto Alexander , Ford Michael J.
Published: August 2021

The bandgap is one of the most fundamental properties of condensed matter. However, an accurate calculation of its value, which could potentially allow experimentalists to identify materials suitable for device applications, is very computationally expensive. Here, active machine learning algorithms are used to leverage a limited number of accurate density functional theory calculations to robustly predict the bandgap of a very large number of novel 2D heterostructures. Using this approach, a database of ≈2.2 million bandgap values for various novel 2D van der Waals heterostructures is produced.
Red‐ and Far‐Red‐Emitting Zinc Probes with Minimal Phototoxicity for Multiplexed Recording of Orchestrated Insulin Secretion
Authors: Zhang Junwei , Peng Xiaohong , Wu Yunxiang , Ren Huixia , Sun Jingfu , Tong Shiyan , Liu Tianyan , Zhao Yiwen , Wang Shusen , Tang Chao , Chen Liangyi , Chen Zhixing
Published: August 2021

Zinc biology, featuring intertwining signaling networks and critical importance to human health, witnesses exciting opportunities in the big data era of physiology. Here, we report a class of red‐ and far‐red‐emitting Zn2+ probes with Kd values ranging from 190 nM to 74 μM, which are particularly suitable for real‐time monitoring the high concentration of Zn2+ co‐released with insulin during vesicular secretory events. Compared to the prototypical rhodamine‐based Zn2+ probes, the new class exploits morpholino auxochromes which eliminates phototoxicity during long‐term live recording of isolated islets. A Si‐rhodamine‐based Zn2+ probe with high turn‐on ratio (>100), whose synthesis was enabled by a new route featuring late‐stage N‐alkylation, allowed simultaneous recording of Ca2+ influx, mitochondrial signal, and insulin secretion in isolated mouse islets. The time‐lapse multicolor fluorescence movies and their analysis, enabled by red‐shifted Zn2+ and other orthogonal physiological probes, highlight the potential impact of biocompatible fluorophores on the fields of islet endocrinology and system biology.
Silica nanoparticle‐modified microcomb electrode for voltammetry detection of osteopontin with high sensitivity
Authors: Shu Hexi , Zhao Liangliang , Li Xiaoxia , Gong Jinpeng , Yin Guorui , Chen Hulin
Published: August 2021

Osteosarcoma is a commonly occurring bone malignancy, and it is the second most common cause of cancer deaths in adolescents and children. A sensitive silica nanoparticle (Si‐NP) modified current‐volt sensor was introduced to identify the osteopontin antigen, a well‐known biomarker for osteosarcoma. Si‐NP was extracted from the rice husk ash and utilized for the surface functionalization on the interdigitated microelectrode sensing surface. Extracted Si‐NP has a spherical shape with uniform distribution, and it is confirmed by field emission scanning electron microscopy and field‐emission transmission electron microscopy. Si‐NP was layered on the electrode surface through a (3‐aminopropyl)triethoxysilane amine linker, and the antibody was immobilized on Si‐NP through a glutaraldehyde linker. Osteopontin was effectively detected on the antibody‐attached surface, and the determination limit was 0.6 ng/mL. The regression was determined asy= 0.9366x− 1.1113 and the R2 value was 0.9331 and the detection limit of osteopontin was 0.6 ng/mL in the range between 0.3 and 5 ng/mL. In addition, control performance with nonimmune antibodies and albumin did not change the current volt, showing the specific osteopontin identification. This research work brings out the easy and cost‐effective method to diagnose osteosarcoma and its etiology.
Three‐dimensional‐poly(lactic acid) scaffolds coated with gelatin/magnesium‐doped nano‐hydroxyapatite for bone tissue engineering
Authors: Swetha Sampath , Balagangadharan Kalimuthu , Lavanya Krishnaraj , Selvamurugan Nagarajan
Published: August 2021

Background

Treatment of critical‐sized bone defects has progressively evolved over the years from metallic implants to more ingenious three‐dimensional‐based scaffolds. The use of three‐dimensional scaffolds for bone regeneration from biodegradable polymers like poly(lactic acid) (PLA) is gaining popularity. Scaffolds with surface functionalization using gelatin (Gel) have the advantages of biocompatibility and cell adhesion. Nano‐hydroxyapatite (nHAp) is one of the most promising implant materials utilized in orthopaedics. The osteogenic potential of the nHAp can be improved by the substitution of magnesium (Mg) ions onto the crystal lattice of nHAp. Thus, the goal of this work was to make three‐dimensional‐PLA scaffolds covered with Gel/Mg‐nHAp for osteogenic effect.

Methods and results

The designed three‐dimensional‐PLA/Gel/Mg‐nHAp scaffolds were attributed to various characterizations for the examination of their physicochemical, mechanical properties, cyto‐compatibility, and biodegradability as well as their ability to promote osteogenesis in vitro. Mouse mesenchymal stem cells (mMSCs) were cytocompatible with these scaffolds. The osteogenic potential of three‐dimensional‐PLA/Gel/Mg‐nHAp scaffolds employing mMSCs was validated at the cellular and molecular levels. The three‐dimensional‐PLA/Gel/Mg‐nHAp scaffolds stimulated the differentiation of mMSCs towards osteoblastic lineage.

Conclusion

Based on these findings, we suggest that the three‐dimensional‐PLA/Gel/Mg‐nHAp scaffolds' osteogenic capability may be advantageous in the mending of bone defects in orthopedic applications.
Prediction of dispositional dialectical thinking from resting‐state electroencephalography
Authors: Huang Kun , Chen Dian , Wang Fei , Yang Lijian
Published: August 2021

This study aims to explore the possibility of predicting the dispositional level of dialectical thinking using resting‐state electroencephalography signals. Thirty‐four participants completed a self‐reported measure of dialectical thinking, and their resting‐state electroencephalography was recorded. After wave filtration and eye movement removal, time‐frequency electroencephalography signals were converted into four frequency domains: delta (1–4 Hz), theta (4–7 Hz), alpha (7–13 Hz), and beta (13–30 Hz). Functional principal component analysis with B‐spline approximation was then applied for feature reduction. Five machine learning methods (support vector regression, least absolute shrinkage and selection operator, K‐nearest neighbors, random forest, and gradient boosting decision tree) were applied to the reduced features for prediction. The model ensemble technique was used to create the best performing final model. The results showed that the alpha wave of the electroencephalography signal in the early period (12–15 s) contributed most to the prediction of dialectical thinking. With data‐driven electrode selection (FC1, FCz, Fz, FC3, Cz, AFz), the prediction model achieved an average coefficient of determination of 0.45 on 200 random test sets. Furthermore, a significant positive correlation was found between the alpha value of standardized low‐resolution electromagnetic tomography activity in the right dorsal anterior cingulate cortex and dialectical self‐scale score. The prefrontal and midline alpha oscillations of resting electroencephalography are good predictors of the dispositional level of dialectical thinking, possibly reflecting these brain structures’ involvement in dialectical thinking.
Effect of electroacupuncture on inhibition of inflammatory response and oxidative stress through activating ApoE and Nrf2 in a mouse model of spinal cord injury
Authors: Dai Ni , Tang Chenglin , Liu Hui , Huang Siqin
Published: August 2021

Introduction

Electroacupuncture protects neurons and myelinated axons after spinal cord injury by mitigating the inflammatory response and oxidative stress, but how it exerts these effects is unclear.

Methods and results

Spinal cord injury was induced in C57BL/6 wild‐type and apolipoprotein E (ApoE) knockout (ApoE–/–) mice, followed by electroacupuncture or ApoE mimetic peptide COG112 treatment. Mice with spinal cord injury suffered loss of myelinated axons and hindlimb motor function through the detections of Basso mouse scale, histology, and transmission electron microscopy; electroacupuncture partially reversed these effects in wild‐type mice but not in ApoE–/–mice. Combining exogenous ApoE administration with electroacupuncture significantly mitigated the effects of spinal cord injury in both mouse strains, and these effects were associated with up‐regulation of anti‐inflammatory cytokines and down‐regulation of pro‐inflammatory cytokines which were detected by quantitative reverse transcription‐polymerase chain reaction. Combination treatment also reduced oxidative stress by up‐regulating ApoE and Nrf2/HO‐1 signaling pathway through the detections of immunofluorescence and western blot analysis.

Conclusions

These results suggest that electroacupuncture protects neurons and myelinated axons following spinal cord injury through an ApoE‐dependent mechanism.
Simplified Derivatives of Dibenzylbutyrolactone Lignans from Hydrocotyle bonariensis as Antitrypanosomal Candidates
Authors: Souza Dalete Christine S. , Costa‐Silva Thais A. , Morais Thiago R. , Brito Juliana R. , Ferreira Edgard A. , Antar Guilherme M. , Sartorelli Patricia , Tempone Andre G. , Lago João Henrique G.
Published: August 2021

The search for the pharmacophore of a bioactive compound, crucial for drug discovery studies, involves the adequate arrangement of different atoms in the molecule. As part of a continuous work aiming discovery of new drug candidates against the protozoan parasite Trypanosoma cruzi, the hexane extract of Hydrocotyle bonariensis was subjected to a bioactivity‐guided fractionation to afford two chemically related dibenzylbutyrolactone lignans – hinokinin (1) and hibalactone (2). Compounds 1 and 2 showed activity against trypomastigote with EC50 values of 17.0 and 69.4 μM, respectively. Compound 1 was also active against the clinically relevant form of the parasite, amastigotes, displaying an EC50 value of 34.4 μM. The structure‐activity relationship (SAR) indicated that the absence of the double bond at C‐7 is a crucial feature for the increment of the antiparasitic activity. The lethal action of the most potent compound 1 was investigated in the trypomastigotes. The fluorescent‐based assay with SYTOX Green demonstrated a significant alteration of the plasma membrane permeability of the parasite. Additionally, compound 1 demonstrated no significant hemolytic activity in mice erythrocytes at 200 μM. To search the pharmacophore, three different simplified compounds – 3,4‐methylenedioxydihydrocinnamic acid (3), 3,4‐methylenedioxydihydrocinnamic alcohol (4) and 3,4‐methylenedioxycinnamic acid (5) – were prepared and tested against T. cruzi. These derivatives displayed EC50 values of 37.2 (3), 25.8 (4) and 73.5 (5) μM against trypomastigotes, and 41.3 (3) and 48.2 (4) μM against amastigotes, whereas compound 5 was inactive. Except for compound 2, which resulted in a CC50 value of 114.5 μM, all compounds showed no mammalian cytotoxicity at 200 μM. An in silico ADMET study was performed and predicted values demonstrated an acceptable drug‐likeness profile for compounds 1–5. Despite the minor reduction in the potency, the simplified derivatives retained the antitrypanosomal activity against the intracellular amastigotes, even with 95 % reduction of their molecular weight. Additionally, in silico studies suggested them as more soluble compounds, making these simplified structures promising scaffolds for optimization studies in Chagas disease.
Gold‐Catalyzed Direct C(sp3)−H Acetoxylation of Saturated Hydrocarbons
Authors: Jo Tae Geun , Klein Johannes E. M. N.
Published: August 2021

In this communication we report our studies towards the development of a gold‐catalyzed direct acetoxylation of C(sp3)−H bonds. We achieve this through the use of the hypervalent iodine reagent PhI(OAc)2 in combination with a simple gold salt (HAuBr4) as the catalyst. Through a comparison of the reactivities of cyclooctane and adamantane we judge the reaction to proceed via hydride transfer. This is further substantiated through computational studies of the relative energies for the anions, radicals and cations derived from C−H bond cleavage of cyclooctane and adamantane relevant to the C−H cleaving step.
The preparation of optically active epineoclausenamide and enantiomeric separation of its racemate
Authors: Yan Yixiao , Zhu Senmei , Luo Xuna , Rao Yu , Su Jinlong , He Guantao , Lin Hansen
Published: August 2021

We synthesized the optically active epineoclausenamide by utilizing chiral reagents, such as R‐α‐methylbenzylamine and S‐α‐methylbenzylamine, for the resolution of the intermediate (trans‐3‐phenyl‐oxiranecarboxylic acid 12), followed by amide exchange, cyclization, and reduction, unlike previously reported methods. The Meerwein–Ponndorf–Verley reduction was used to asymmetrically reduce neoclausenamidone. A plausible reduction mechanism of this method was elucidated. Thereafter, high‐performance liquid chromatography (HPLC) was investigated for the resolution of the epineoclausenamide enantiomers. HPLC was also used to determine the optical purity of these isomers. Two chiral stationary phases (CSPs) for separating the enantiomers were compared. Different mobile phase compositions were tested at 298.15 K. The results showed that the best separation was obtained when the mobile phase was composed of n‐hexane and isopropanol (IPA) (75/25, v/v), the racemate was separated on a Chiralcel OJ‐H column, and the flow rate was 1.0 mL/min at a wavelength of 210 nm and a temperature of 25°C. The enantiomeric ratio (e.r.) values of both the synthetic (−)‐epineoclausenamide and (+)‐epineoclausenamide were 1.3(+):98.7(−) and 99.3(+):0.7(−), respectively. In this study, a new synthetic route was designed with a yield of 12.3–14.1%, and a quick (8 min) effective separation method was obtained. This provides basis for pharmacological research and quality control of clausenamide analogues.
Extreme quantile estimation for partial functional linear regression models with heavy‐tailed distributions
Authors: Zhu Hanbing , Li Yehua , Liu Baisen , Yao Weixin , Zhang Riquan
Published: August 2021

In this article, we propose a novel estimator of extreme conditional quantiles in partial functional linear regression models with heavy‐tailed distributions. The conventional quantile regression estimators are often unstable at the extreme tails due to data sparsity, especially for heavy‐tailed distributions. We first estimate the slope function and the partially linear coefficient using a functional quantile regression based on functional principal component analysis, which is a robust alternative to the ordinary least squares regression. The extreme conditional quantiles are then estimated by using a new extrapolation technique from extreme value theory. We establish the asymptotic normality of the proposed estimator and illustrate its finite sample performance by simulation studies and an empirical analysis of diffusion tensor imaging data from a cognitive disorder study.
Cover
Authors: Ono Shoichiro
Published: August 2021

The front cover image is based on the Editorial Diversification of the calponin family proteins by gene amplification and repeat expansion of calponin‐like motifs by Shoichiro Ono., https://doi.org/10.1002/cm.21683.

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Drug Repurposing for the SARS‐CoV‐2 Papain‐Like Protease
Authors: Cho Chia‐Chuan , Li Shuhua G. , Lalonde Tyler J. , Yang Kai S. , Yu Ge , Qiao Yuchen , Xu Shiqing , Ray Liu Wenshe
Published: August 2021

As the pathogen of COVID‐19, SARS‐CoV‐2 encodes two essential cysteine proteases that process the pathogen's two large polypeptide products pp1a and pp1ab in the human cell host to form 15 functionally important, mature nonstructural proteins. One of the two enzymes is papain‐like protease or PLPro. It possesses deubiquitination and deISGylation activities that suppress host innate immune responses toward SARS‐CoV‐2 infection. To repurpose drugs for PLPro, we experimentally screened libraries of 33 deubiquitinase and 37 cysteine protease inhibitors on their inhibition of PLPro. Our results showed that 15 deubiquitinase and 1 cysteine protease inhibitors exhibit strong inhibition of PLPro at 200 μM. More comprehensive characterizations revealed seven inhibitors GRL0617, SJB2‐043, TCID, DUB‐IN‐1, DUB‐IN‐3, PR‐619, and S130 with an IC50 value below 40 μM and four inhibitors GRL0617, SJB2‐043, TCID, and PR‐619 with an IC50 value below 10 μM. Among four inhibitors with an IC50 value below 10 μM, SJB2‐043 is the most unique in that it does not fully inhibit PLPro but has a noteworthy IC50 value of 0.56 μM. SJB2‐043 likely binds to an allosteric site of PLPro to convene its inhibition effect, which needs to be further investigated. As a pilot study, the current work indicates that COVID‐19 drug repurposing by targeting PLPro holds promise, but in‐depth analysis of repurposed drugs is necessary to avoid omitting critical allosteric inhibitors.
Increasing referral of at‐risk women for genetic counseling and BRCA testing using a screening tool in a community breast imaging center
Authors: Arun Banu K. , Peterson Susan K. , Sweeney Lilian E. , Bluebond Rachel D. , Tidwell Rebecca S. S. , Makhnoon Sukh , Kushwaha Anne C.
Published: August 2021

Background

Genetic evaluation and testing for hereditary breast and ovarian cancer (HBOC) remain suboptimal. The authors evaluated the feasibility of using a screening tool at a breast imaging center to increase HBOC assessment referrals.

Methods

A brief questionnaire based on the National Comprehensive Cancer Network HBOC genetic counseling referral guidelines was developed and added to the standard intake forms of patients undergoing mammography at a community breast imaging center from 2012 through 2015. Patients who met the criteria in the guidelines were referred for genetic counseling.

Results

A total of 34,851 patients were screened during the study period, and 1246 (4%) patients were found to be eligible for referral; 245 of these patients made a genetic counseling appointment, and 142 patients received genetic counseling. Forty patients (28%) had a personal history of breast cancer but were not previously tested. Following counseling, 105 patients were tested for BRCA1/2. Eight patients (8%) tested positive for a pathogenic mutation and nine (9%) had a variant of unknown significance. Although they tested negative, many patients met the criteria to add breast magnetic resonance imaging to their screening due to greater than 20% lifetime breast cancer risk based on their family cancer history. This study led to improved clinical risk management in 67% of the patients who underwent genetic counseling.

Conclusions

This study shows that large‐scale screening of patients for HBOC syndromes at time of breast imaging is practical and highly feasible. The screening tool identified women with actionable BRCA1/2 mutations and mutation‐negative but high‐risk women, leading to significant changes in their risk management; these women would otherwise have been missed.

Lay Summary

Hereditary breast and ovarian cancer (HBOC) caused by pathogenic mutations in breast cancer genes (BRCA1/BRCA2) increase an individual's lifetime risk of getting HBOC.

Identifying these high‐risk individuals and using proven preventive clinical risk management strategies can significantly reduce their lifetime risk of HBOC.

Using an innovative family cancer history questionnaire, 34,000 women were screened at a community breast imaging center, and genetic counseling and testing were provided to eligible women from the screening.

Several women at high risk for HBOC were identified and this led to positive clinical risk management changes.

These women would have been missed if not for intervention.
Early life stress alters emotional learning in a sex‐ and age‐dependent manner with no impact on emotional behaviors
Authors: Zanta Natália C. , Suchecki Deborah , Girardi Carlos Eduardo Neves
Published: August 2021

Neonatal adversity can impact neurodevelopmental trajectories. This study examined the long‐term effects of maternal deprivation on day 9 (DEP9), associated or not to a stressor (saline injection [SAL]), on contextual fear conditioning (Experiment 1) and emotional behaviors (Experiment 2) in Wistar rats. Whole litters were either assigned to DEP9 or control groups, and on day 10, half of the litters in each group received an SAL or not (NSAL). DEP9‐SAL male adolescents showed the longest freezing time and DEP9 adult males froze more than females. Females exhibited less anxiety‐like behavior than males; DEP9‐SAL females spent more time in the open arms and DEP9 males visited less the extremity of the open arm in the elevated plus maze. Early life stress increased conditioned and innate fear in males, but not in females, indicating a clear sexual dimorphism in the response to potentially threatening stimuli.
Genetic differential susceptibility to the parent–child relationship quality and the life span development of compassion
Authors: Dobewall Henrik , Keltikangas‐Järvinen Liisa , Saarinen Aino , Lyytikäinen Leo‐Pekka , Zwir Igor , Cloninger Robert , Raitakari Olli T. , Lehtimäki Terho , Hintsanen Mirka
Published: August 2021

The development of compassion for others might be influenced by the social experiences made during childhood and has a genetic component. No research has yet investigated whether the parent–child relationship quality interacts with genetic variation in the oxytocin and dopamine systems in predicting compassion over the life span. In the prospective Young Finns Study (N= 2099, 43.9% men), we examined the interaction between mother‐reported emotional warmth and intolerance toward their child assessed in 1980 (age of participants, 3–18 years) and two established genetic risk scores for oxytocin levels and dopamine signaling activity. Dispositional compassion for others was measured with the Temperament and Character Inventory 1997, 2001, and 2012 (age of participants, 20–50 years). We found a gene–environment interaction (p= .031) that remained marginally significant after adjustment for multiple testing. In line with the differential susceptibility hypothesis, only participants who carry alleles associated with low dopamine signaling activity had higher levels of compassion when growing up with emotionally warm parents, whereas they had lower levels of compassion when their parents were emotionally cold. Children's genetic variability in the dopamine system might result in plasticity to early environmental influences that have a long‐lasting effect on the development of compassion. However, our findings need replication.
Morphine exposure alters Fos expression in a sex‐, age‐, and brain region‐specific manner during adolescence
Authors: Figueroa C. , Yang H. , DiSpirito J. , Bourgeois J. R. , Kalyanasundaram G. , Doshi I. , Bilbo S. D. , Kopec A. M.
Published: August 2021

Data in both humans and preclinical animal models clearly indicate drug exposure during adolescence, when the “reward” circuitry of the brain develops, increases the risk of substance use and other mental health disorders later in life. Human data indicate that different neural and behavioral sequelae can be observed in early versus late adolescence. However, most studies with rodent models examine a single adolescent age compared to a mature adult age, and often only in males. Herein, we sought to determine whether the acute response to the opioid morphine would also differ across adolescence, and by sex. By quantifying Fos positive cells, a proxy for neural activity, at different stages during adolescence (pre‐, early, mid‐, and late adolescence) and in multiple reward regions (prefrontal cortex, nucleus accumbens, caudate/putamen), we determined that the neural response to acute morphine is highly dependent on adolescent age, sex, and brain region. These data suggest that heterogeneity in the consequences of adolescent opioid exposure may be due to age‐ and sex‐specific developmental profiles in individual reward processing regions. In future studies, it will be important to add age within adolescence as an independent variable for a holistic view of healthy or abnormal reward‐related neural development.
Marine Algal Sensitivity to Source and Weathered Oils
Authors: Softcheck Katherina A.
Published: August 2021

After the Deepwater Horizon oil spill in 2010, toxicity tests were conducted using 4 microalgae (Dunaliella tertiolecta, Skeletonema costatum, Isochrysis galbana, and Thalassiosira pseudonana) and one macroalga (Ectocarpus siliculosus) to study potential impacts on phytoplankton and other primary producers in the Gulf of Mexico and characterize species sensitivity. Tests were performed with Corexit 9500 and fresh source oil and weathered oil samples collected from the field during the Deepwater Horizon oil spill. Because crude oils are mixtures of poorly water-soluble hydrocarbons, dosing was performed using water-accommodated fractions (WAFs) and chemically enhanced (CE) WAFs with the addition of dispersant at a 1:20 dispersant:oil ratio using standard toxicity testing protocols. Exposure media were analyzed for volatile organic compounds, parent and alkylated polycyclic aromatic hydrocarbons, and saturated hydrocarbon compounds. Toxicity was reported as no-observable effect concentration and median effect concentration (EC50) values for average specific growth rate based on nominal percent dilution of stock solution WAFs and sum of dissolved oil toxic units for WAF/CEWAF tests. The macroalga and green alga D. tertiolecta were largely unaffected by any WAF or CEWAFs tested. Isochrysis galbana was found to be the most sensitive species overall with significant growth rate inhibitions for dispersant and all the WAFs/CEWAFs tested. Physically dispersed source oils were generally more toxic than weathered oils. The protectiveness of the chronic toxic units was effective at identifying observed algal growth rate inhibitions across algal species and oil types despite the impact of dispersants.  Environ Toxicol Chem 2021;40:2742–2754. © 2021 SETAC
Review of proposed different irradiation methods to inactivate food‐processing viruses and microorganisms
Authors: Shahi Sharifeh , Khorvash Reza , Goli Mohammad , Ranjbaran Seyed Mohsen , Najarian Afsaneh , Mohammadi Nafchi Abdorreza
Published: August 2021

Coronaviruses, which have been enveloped nonsegmented positive‐sense RNA viruses, were first mentioned in the mid‐1960s and can attack people as well as a wide range of animals (including mammals and birds). Three zoonotic coronaviruses have been identified as the cause of large‐scale epidemics over the last two decades: Middle East respiratory syndrome (MERS), severe acute respiratory syndrome (SARS), and swine acute diarrhea syndrome (SADS). Epithelial cells in the respiratory and gastrointestinal tract are the principal targeted cells, and viral shedding occurs via these systems in diverse ways such as through fomites, air, or feces. Patients infected with the novel coronavirus (2019‐nCoV) reported having visited the Wuhan seafood wholesale market shortly before disease onset. The clinical data on established 2019‐nCoV cases reported so far indicate a milder disease course than that described for patients with SARS‐CoV or MERS‐CoV. This study aimed to review radiation inactivation of these viruses in the food industry in three sections: visible light, ionizing radiation (alpha ray, beta ray, X‐ray, gamma ray, neutron, plasma, and ozone), and nonionizing radiation (microwave, ultraviolet, infrared, laser light, and radiofrequency). Due to the obvious possibility of human‐to‐human and animal‐to‐human transmission, using at least one of these three methods in food processing and packaging during coronavirus outbreaks will be critical for preventing further outbreaks at the community level.