bluuebunny/crossref_metadata_2025 huggingface dataset:
NEED, SCOPE AND LIMITATIONS OF ANIMAL STUDY IN PERSPECTIVE OF AYURVEDA: A REVIEW
Authors: Chavan Sucheta S , Tawalare Kiran , Mishra Snehvibha
Published: October 2022

Ayurveda is a goldmine for researchers. Unfortunately, very few researches are planned with a comprehensive approach. Animals have been used repeatedly throughout the history of biomedical research analysis. The utilization of non-human animals in biomedical research has made an essential contribution from precedent days. These animal experiments advance understanding of anatomy, physiology, pathology, pharmacology, and various medical fields. However, natural laboratory-based new research is still awaited. Our objective was to compile the most recent data on animal study's needs, scope and limitations. Also, we tend to overlook how we conduct a department-wise animal study, the ethics of the animal study, and the similarities between animals and man and their unique mechanisms. We conduct a narrative review. There is a need and scope for animal study in medical bioscience because a cure for a disease proves the safety and efficacy of new treatments attained through animal testing. There are also some limitations in animal studies, like loss of biological variability or predictivity from the utilization of inbred strains, young animals, restriction to single sexes, and inadequate cluster sizes. Also, there are so many department-wise uses and limitations of animal study. Conclusion: Animal study proves beneficial for the future because animals are often used in medical research to investigate the progression of the disease, test new drugs, surgeries, etc. But before that, we must always study the ethics of animal research to avoid unskilled, pseudoscientific and needlessly repetitive studies that bring on reserve damage to laboratory animals.
A REVIEW ON VIKARA DHATU VAISHAMYAM’: AN APPRAISAL OF THE STATE OF DOSHAS AND DHATUS IN THE PATHOGENESIS OF DISEASES IN LIGHT OF CHARAKA SAMHITA
Authors: Majumder Bijita , Ray Sukalyan
Published: October 2022

As all the dosha, dhatu and mala are responsible for the retention of our body's homeostasis, all these three factors can be referred to as dhatu - ‘the element which holds up our body. Any deviation from the normal qualitative and quantitative state of these three elements can be referred to as dhatu vaishmaya, which is responsible for pathophysiologic changes in our body, which finally leads to the causation of diseases known as vikara. This deviation from the normal state can be in two ways - either in the form of aggravation/increment (known as vriddhi or prakopa) or regression/depletion (known as kshaya). In this article, the authors have tried to evaluate the state of dosha and dhatus during the pathological process of diseases, whether they remain in aggravated condition or depleted condition. From various textual understandings and evaluations of diseases' pathological processes and clinical features, it can be observed that dosha remains in its aggravated state during the pathogenesis of diseases and when it afflicts the dhatu - this results in the depletion of dhatu. Apart from two or three exceptions, in all types of conditions, this phenomenon of dosha vriddhi and dhatu kshaya can be observed conceptually as well as clinically. Thus, it can be concluded that the verse ‘Vikara Dhatu Vaishamyam’ refers to the altered state of dosha vriddhi and dhatu kshaya, which is responsible for the causation of vikara, i.e., diseases.
RAKTAMOKSHANA (BLOODLETTING), A MULTI-DIMENSIONAL PREVENTIVE AND CURATIVE APPROACH IN ORAL DISORDERS: A REVIEW
Authors: Bhat Akshatha K , Maradka Asha , K Santhosh
Published: October 2022

Mukha is considered one of the essential parts of urdhwajatru because it reflects the body's health by acting as the gateway of the alimentary canal. Fast food culture, unhealthy habits like smoking and improper oral hygiene have caused irreversible damage to human health, resulting in different oral cavity diseases. In Ayurveda, mukharoga has been elaborately explained with its symptoms and treatment, which can be well co-related to present oral cavity diseases mentioned in contemporary science. In our classics, various treatment modalities have been explained for different oral cavity diseases, from lips to throat. Raktamokshana is the primary line of treatment mentioned for mukharogas, followed by pratisarana, kavala, gandusha, shastra karma and oral medications. Acharya Vagbhata highlights the importance of Raktamokshana in mukha, danta, dantamoola and gala roga. Since all these diseases are kapha-rakta in origin, they require frequent bloodletting. Specifically, in mukharoga, bloodletting as a method is indicated in puti aasya, paaka of oshtha. In these diseases, bloodletting should be done by shringa, jalouka, and alabu or by cutting the sira. There are many kinds of research undertaken to study the action of bloodletting using leeches and have found plenty of beneficial actions like analgesic, anti-inflammatory and antibacterial activity. Overall, Raktamokshana is a very effective line of treatment in most of the mukharogas, curing the disease and preventing further recurrence.
CONCEPT OF SHODHANA IN AYURVEDIC PHARMACEUTICS: A REVIEW
Authors: Shamsudheen Shamja C. , Gupta KL Virupaksha , Saravanan B.
Published: October 2022

Rasaushadhis (herbomineral preparations) are a treasure in Ayurveda. They assure fast recovery of diseases as compared with plant-based medicine. These medicines require lengthy processing before conversion into admissible forms. The processes like Shodhana (purification), Marana (incineration), Amrutikarana (nectarization), Bhasmikarana, Satwapatana etc., are adopted to achieve this. Before the metals and minerals are used for therapeutic benefit, it is necessary to eliminate all the physical, chemical, and toxic impurities. Shodhana is the first and most crucial procedure adopted to achieve this. References from Rasashastra textbooks like Rasa Ratna Samuchaya (RRS), Rasa Tarangini (RT), and Ayurveda prakasha (AP) are reviewed and incorporated in this article. Various methods like Nirvapa, Swedana, Pachana, Bhavana, Dhalana, Nimajjana, etc., are adopted for shodhana. These methods are done with the help of instruments like Dolayantra, Swedani Yantra, Lohadarvi (iron spoon), Vanka Nala etc. Various media like Kanji, Takra, Aranala, Gomutra etc., are used depending on the nature of the materials. Shodhana removes the physical and chemical impurities and potentiates the drug's efficacy, which, in turn, reduces the side effect of the drug. Shodhana also impregnates organic materials and their properties into inorganic drugs to facilitate their utilization by the body.
A REVIEW ON IMMUNOMODULATORY PLANTS IN INDIA AND THEIR SIGNIFICANCE
Authors: Sruthi V. , Rao G. Baba Shankar
Published: October 2022

An immunomodulator is a substance that either suppresses or stimulates immunity components. Currently, immune system modulation using different herbal constituents is an investigational scientific subject. Several herbal plants belonging to India were found to have an immunomodulatory effect. Various therapeutic effects of plant extracts were found because of their wide range of immunomodulatory effects. Plants’ immunomodulatory activities are due to phytochemicals like lactones, flavonoids, alkaloids, and glycosides. A remarkable rise in understanding the phytoconstituents' knowledge and their effects and side effect began recently. Plants like Morus alba, Acacia catechu, Tinospora cordifolia, Allium sativum, Mangifera indica etc., have gained attention. This article mainly focuses on several herbal plants in India that enhance and suppress impaired immune systems under unfavourable conditions.
A Review of the Therapeutic Potentials of Stem Cells, Fibroblast Growth Factors and T-cells in Regenerative Medicine
Authors: Okikiade Adedeji , Osharode Aromedonghene , Oloye-Afolayan Olayinka , Ogunesan Damisola , Adijat Oyewole , Chibuike K. Ubah , Browne Kevin
Published: October 2022

The human body is a complex structure with the innate ability to protect, defend, repair, and heal after damage or disease. For decades, medicine has faced problems that need the evolution of standard treatments and finding a way to accelerate the regenerative capabilities of the body, which possibly would not just treat but also cure certain diseases that previously had no cure. The question researchers have pondered on is whether or not it was possible as humans to use the body's innate healing power to our advantage and clinically accelerate or modify it to upgrade the treatment of certain diseases. The answer they found was in Regenerative Medicine (RM).

Historically the term regenerative medicine was found for the first time in a paper published in 1992 by Leland Kaiser. He made a list of approaches that would impact the future of hospitals. However, it is widely believed to have been coined during a 1999 conference on Lake Como by William Haseltine in an attempt to describe a novel field of medicine that combined knowledge from subjects like cell transplant, biochemistry, nanotechnology, prosthetics biomechanics, tissue engineering, and stem cell biology.

Regenerative Medicine is a relatively new field of clinical applications and research that is focused on the development of therapies like tissue engineering and stem cell technologies to repair, regenerate or replace defective, aged, injured, diseased, or permanently damaged organs, tissues or cells in order to restore them to their normal function.

It is important to note that RM has rapidly become one of the top treatment options for acute and chronic injuries, congenital diseases, and a wide range of acute and chronic diseases. It is more than just a field of medicine involving basic replacement therapies or traditional transplantation; it applies approaches like gene therapy, reprogramming of cell types, stem cell transplantation, and the use of soluble molecules, tissue engineering, and lots more.

The review article focuses on the therapeutic effects of fibroblast growth factors (FGFs), adipose-derived stem cells (ADSCs), and regulatory T cells (Tregs), and the possible role they play in tissue regeneration. They are apparently useful in the treatment of myriads of diseases expectedly having no cure.
Chi-Square Test in Time Series Data
Authors: Dozie Kelechukwu C. N. , Ihekuna Stephen O.
Published: October 2022

This study examines the application of Chi-Square test in time series data which considers the mixed model structure and linear trending curve. The Chi-Square test is applied to the seasonal variances of the Buys-Ballot table. The emphasis is to assess the validity of the Chi-Square test using empirical examples. One hundred simulated numerical examples are used to illustrate the applicability of the Chi-Square test. Using empirical example, the Chi-Square test successfully recorded 100% of times for the mixed model. This expresses a high degree of confidence in the Chi-Square test.
Factors Predicting the Mathematics Performance of Grade 8 Students in the New Normal
Authors: Tobias Cristian A. , Diego Crispina V.
Published: October 2022

Mathematics performance has been recognized as vital in the curricula in most of the country not only for academic success but also for its efficient application in everyday life. The study aimed to determine a significant relationship between the student, teacher, environmental, and parent involvement factors and students’ mathematics performance in a Catholic university for the Academic Year 2020-2021. Also, it determined which factors predict the mathematics performance of students. Using descriptive-correlational research design, 123 Grade 8 students answered a researcher-made test questionnaire to assess students' level of mathematics performance; these were interpreted using the Department of Education’s scale of standard.  Furthermore, a researcher-made survey questionnaire was used to examine the level of extent of the four factors influencing the students’ mathematics performance, the correlation between these factors and students’ mathematics performance, and predictors of students’ mathematics performance. The assembled information was dealt with measurably utilizing mean, standard deviation, Kruskal-Wallis, Pearson product-moment correlation, Spearman's rho, and multiple linear regression. Results revealed that students’ level of mathematics performance was fairly-satisfactory (M=79.77, SD=8.96). The extent of influence of the factors is moderate (M=3.28, SD=0.33). There is a significant correlation between the extent of influence of factors as a whole and Mathematics performance [r(121)=0.235, p=0.009]. The results of the regression indicated that the predictor explained 7.3% of the variance [F(1, 121)=9.540, p=0.002, R2=0.073)]. The individual predictors were further examined and indicated that the teacher factor [β=6.440, t=3.089, p=0.002] significantly predicts Mathematics performance. This study provides significant insights into the vital role teachers play in finding a lasting solution to the students' perennial poor performance issues in mathematics in this new normal.
Sensory Evaluation of Different Value Added Products of Aonla (Emblica officinalis G.) during Storage
Authors: Uikey Ashwini , Gurjar P. K. S. , Rathour Shubham
Published: October 2022

A research experiment was conducted during the year 2019-20 and 2020-21 in the Fruit and Vegetable Processing Unit Laboratory, Department of Horticulture, College of Agriculture, Gwalior with seven different varieties of aonla viz., NA-4, NA-5, NA-6, NA-7, NA-10, Laxmi and Chakaiya. It was studied about the preparation of various value added products such as aonla toffee, with beverages like nectar and squash. Observations were recorded up to storage period of six months at ambient conditions. This study is analyzed in a completely randomised design with three replications. Laxmi and Chakaiya varieties were found superior with respect to colour, appearance, taste and aroma as well as flavour. It has been noticed that the overall acceptability of processed products have been found significant with the storage intervals such as 30, 60, 90 and 120 days. As far as sensory evaluation of different aonla products was concerned, the Laxmi and Chakaiya varieties are found to be superior for the purpose of the processing industry.
Assessment of Factors on Assimilation of Climate Smart Agricultural Practices in the North Eastern Hill Region of India: A SWOT-AHP Analysis
Authors: Devi Mayanglambam Victoria , Singh Rajkumar Josmee
Published: October 2022

Aims: To appraise the factors for smooth assimilation of Climate Smart Agriculture (CSA) practices in the North Eastern Hill Region (NEHR) of India.

Study Design: Exploratory Research Design was followed for the study.

Place and Duration of Study: The study was conducted in the three states Arunachal Pradesh, Manipur and Meghalaya representing the Tropical, Sub-Tropical and Temperate Agro-Climatic Zone respectively in the region. The study was conducted during 2020-21.

Methodology: A Total of twenty-six (26) Extension agents including the Scientist of Indian Council of Agricultural Research (ICAR) centres, faculty of Colleges under Central Agricultural University, Imphal, and Subject Matter Specialists (SMS) in the KVKs who are working for more than three years in Climate change were selected purposively for the study. The study employed Delphi technique. On the subsequent three (3) iterations only seventeen (17) subject matter experts/specialists, scientist and faculties had responded for the study. To identify the factors of assimilation, Strengths, Weaknesses, Opportunities, Threats- Analytic Hierarchy Process (SWOT- AHP) analysis was employed in the study.

Results: The study uncovered that ‘Crop and Livestock Diversification due to existence of different Agro-Climatic Zones’; ‘Overly long Return on Investment span of CSA technologies on Adaptation and mitigation of Climate Change Consequences’; ‘Successful Market-aligned supply chain infrastructure from farm to fork’; and ‘Food insecurity & unsustainable livelihood due to negative impact of Climate Change on agriculture & allied enterprises’ were the most important Strengths, Weaknesses, Opportunities and Threats, respectively determining the assimilation of CSA practices in the region. The judgement given by the extension agents were found acceptable with inconsistency ratio below 10%.

Conclusion: Reflecting the reliable judgement amongst the experts, it shows a helpful scope for modifying the CSA practices that are developed in the region and need to focus on the bottleneck that need to be tackle for successful dissemination of CSA practices in the region.
A Quantitative Assessment of the Impact of Nutritional Choices, Quality of Sleep and Physical Activity on the General Health of Staff and Students at the All Saints University School of Medicine, Dominica
Authors: Morebise Olugbenga , Khan Shakeel Ahmed , Abiodun Silvanus Ifeoluwa , Ayinde Bolaji , Adewara Enoch , Ike Emeka , Dupuis Derma , Meyof Sabeth , Arogundade Oyinkansola , Aneke Chizoba
Published: October 2022

This study utilized a quantitative approach to investigate the impact of nutritional choices, quality of sleep and physical activity on the general health of staff and students at the All Saints University School of Medicine, Dominica. Seventy-seven people (14 staff members and 63 students) participated in the survey. The Nutritional Assessment Instrument of the Government of Northwest Territories was utilized to assess the nutritional choices of participants, the Pittsburgh Sleep Quality Index (PSQI) was used to determine the quality of sleep, the International Physical Activity Questionnaire—Short Form was used to assess the physical activity while the SF-36 Questionnaire was utilized to assess the general health of participants. The mean general health of participants was 75.46 (SD = 15.44) out of a maximum of 100. Nutritional choices (r = .270, P = .018), quality of sleep (r = .387, P <.001) and physical activity (r = .237, P = .040) all had significant positive correlations with general health. A regression analysis indicated that quality of sleep (B = 13.881, p<.001) and nutritional choices (B= 10.352, p= 0.002) were the best predictors of general health while physical activity (B = 4.099, p = .063) also had a weak but non-significant positive contribution. While males had a higher mean general health compared to females, this difference was not statistically significant (P>.05). The study recommends an improvement in sleep quality, nutritional choices and physical activity and recommends, among others, the following: education of students on the need to observe good nutritional choices, quality of sleep and exercises; establishment of a cafeteria that offers healthy foods and snacks, and the creation of a Fitness Club in the University. The authors recommend that a similar study should be conducted in other institutions, especially governmental agencies and religious organizations in Dominica, as well as in other Caribbean medical universities. A further study into how nutritional choices, quality of sleep and physical activity are related to specific non-communicable diseases such as obesity, high blood pressure and diabetes mellitus in the Caribbean, using both quantitative and qualitative approaches, is also recommended.
Accessibility to Integrated Community Case Management of Childhood Pneumonia Services among Caregivers in Kisii County, Kenya
Authors: Mwambi Dennis Oroo , Osero Justus O. S. , Mwanzo Isaac , Cheboi Solomon
Published: October 2022

Pneumonia is the leading cause of childhood illness and mortality worldwide. The number of children under five with pneumonia in Kisii County, Kenya, was 10% compared to the national average of 9% despite the integrated Community Case Management (iCCM) roll out. In order to identify factors associated with caregivers' access to iCCM services, a study was conducted.

Materials and Methods: Qualitative and quantitative approaches were used in this descriptive cross-sectional study. Purposive sampling was utilized to choose 10 informants while multistage and random sampling was applied to select 330 caregivers. Thematic content analysis and discourse analysis techniques were used to analyse qualitative data, while Statistical Package for Social Science (SPSS) version 22 was used in quantitative data.

Results: Only 33.6% of caregivers accessed iCCM for childhood pneumonia services. In 49% of cases, CHVs was the first point of contact after onset of pneumonia symptoms, with only 31.2% seeking help within 24 hours. 96% of CHVs did not follow the recommended iCCM diagnostic protocols, and only 34.8% prescribed antibiotics. Age (0.011), religion (0.007), and marital status (0.024) were significantly associated with access to iCCM. Business persons were 2.97 times (OR 2.972; CI 1.232,7.167; P= 0.015) more likely to access iCCM than farmers. Caregivers who perceived pneumonia to be severe were 3.03 more likely to access ICCM (OR 3.039;CI 1.703,5.424; P< 0.001) than opposite peers. Respondents who didn't think pandemics affected access were 10% (OR 0.119; CI .058,0.246; P<.0.001) more likely to access iCCM.

Conclusion: Access to iCCM was low and Community health volunteers (CHVs) were not the first point of care for pneumonia in children. Evidence of poor performance by CHVs in the areas of diagnosis, treatment, and the administration of antibiotics suggests that iCCM needs more monitoring and oversight.
Trends of Drug Practices in Pakistani National Athletes for Amplification of Game / Sport Performance
Authors: Javed Saeed , Baloch Aurangzaib Manzoor , Naseer Abida , Hamdani Syed Muhammad Zeshan Haider , Kousar Tehmina , Khan Imran Ullah , Asghar Adnan , Javed Waheed , Shariff Abd Rahim Mohd
Published: October 2022

Aims: The primary aim of the present research was to provide awareness about the latest trends of drug practices of national athletes of Pakistan for the improvement of their sport performance.

Methodology: The samples were national athletes belonging to various sports departments of national level. The athletes were selected using snowball and convenient sampling approaches. The questionnaire employed for the data collection was self-administered. With the optimistic consent of the athletes, 80 questionnaires were dispatched at their home addresses. Therefore, 62 athletes (77.5%) returned the filled questionnaires. The requisite information of all filled questionnaires was coded in SPSS-26 software to get the desired results. Moreover, descriptive statistics through frequencies and percentages was executed to draw the findings and further discussions of the present study.

Results: The mean age of the national athletes was noted 34.17 years with 2.8 std. deviation and the age range was found between 30 to 38 years. The descriptive statistics of drug practices by national athletes calculated through occasionally, sometimes and frequently. Majority of the national athletes followed and practiced the trends of drugs while participating in their national games and championships to enhance their sport performance to approach the winning position and get the medals.

Conclusion: It was concluded that athletes may not aware the side effects and hazards of these drug practices using anabolic steroids, charas, marijuana, aspirin, cocaine, and heroin. National associations and federations should conduct seminars and awareness workshops for the athletes prior to their participation in sport competitions so that national athletes may save themselves from the side effects and afterwards physical damages.
Particularization of the Sequence of Spacetime/Intrinsic Spacetime Geometries and Associated Sequence of Theories in Metric Force Fields in the Four-world Picture to the Gravitational Field I
Authors: Joseph O. Akindele Adekugbe
Published: October 2022

The two stages of evolutions of metric spacetime and intrinsic metric spacetime and the associated spacetime/intrinsic spacetime geometries in long range metric force fields, derived in the four-world picture in previous articles, are particularized to the gravitational field. The theory of relativity on flat four-dimensional gravitational-relativistic metric spacetime \((\mathbb{E}^3, c_s t\)) and the theory of intrinsic relativity on the underlying flat two-dimensional gravitational-relativistic intrinsic metric spacetime \((\varnothing \rho, \varnothing c_s \varnothing t\)), due to the presence of a long range metric force field in spacetime, as well as the absolute intrinsic metric theory (of the metric force field) on the curved 'two-dimensional' absolute intrinsic metric spacetime \((\varnothing \hat{\rho}, \varnothing \hat{c}_s \varnothing \hat{t}\)) with absolute intrinsic metric tensor \(\varnothing \hat{g}_{i k}\), all of which evolve at two stages of evolutions of metric spacetimes and intrinsic metric spacetimes in long range metric force fields in general, developed in the previous articles, are adapted to the gravitational field.They become the theory of gravitational relativity (TGR) on the flat four-dimensional relativistic metric spacetime, the theory of intrinsic gravitational relativity (TøGR) on the underlying flat two-dimensional relativistic intrinsic metric spacetime and the metric theory of absolute intrinsic gravity (MA \(\varnothing\) G) on the curved 'two-dimensional' absolute intrinsic metric spacetime, which evolve at two stages of evolutions of metric spacetime and intrinsic metric spacetime in a gravitational field of arbitrary strength. The basic aspects of these coexisting theories in the gravitational field are developed.
Evaluation of the Association of Platelet Count, Mean Platelet Volume, and Platelet Transfusion With Intraventricular Hemorrhage and Death Among Preterm Infants
Authors: Chen Chong , Wu Sicheng , Chen Jia , Wu Jinghui , Mei Yabo , Han Tao , Yang Changshuan , Ouyang Xilin , Wong May Chun Mei , Feng Zhichun
Published: October 2022

Importance

Platelet transfusion is commonly performed in infants to correct severe thrombocytopenia or prevent bleeding. Exploring the associations of platelet transfusion, platelet count (PC), and mean platelet volume (MPV) with intraventricular hemorrhage (IVH) and in-hospital mortality in preterm infants can provide evidence for the establishment of future practices.

Objectives

To evaluate the associations of platelet transfusion, PC, and MPV with IVH and in-hospital mortality and to explore whether platelet transfusion–associated IVH and mortality risks vary with PC and MPV levels at the time of transfusion.

Design, Setting, and Participants

This retrospective cohort study included preterm infants who were transferred to the neonatal intensive care unit on their day of birth and received ventilation during their hospital stay. The study was conducted at a neonatal intensive care unit referral center in Beijing, China, between May 2016 and October 2017. Data were retrieved and analyzed from December 2020 to January 2022.

Exposures

Platelet transfusion, PC, and MPV.

Main Outcomes and Measures

Any grade IVH, severe IVH (grade 3 or 4), and in-hospital mortality.

Results

Among the 1221 preterm infants (731 [59.9%] male; median [IQR] gestational age, 31.0 [29.0-33.0] weeks), 94 (7.7%) received 166 platelet transfusions. After adjustment for potential confounders, platelet transfusion was significantly associated with mortality (hazard ratio [HR], 1.48; 95% CI, 1.13-1.93; P = .004). A decreased PC was significantly associated with any grade IVH (HR per 50 × 103/μL, 1.13; 95% CI, 1.05-1.22; P = .001), severe IVH (HR per 50 × 103/μL, 1.16; 95% CI, 1.02-1.32; P = .02), and mortality (HR per 50 × 103/μL, 1.74; 95% CI, 1.48-2.03; P < .001). A higher MPV was associated with a lower risk of mortality (HR, 0.83; 95% CI, 0.69-0.98; P = .03). The platelet transfusion–associated risks for both IVH and mortality increased when transfusion was performed in infants with a higher PC level (eg, PC of 25 × 103/μL: HR, 1.20; 95% CI, 0.89-1.62; PC of 100 × 103/μL: HR, 1.40; 95% CI, 1.08-1.82). The platelet transfusion–associated risks of IVH and mortality varied with MPV level at the time of transfusion.

Conclusions and Relevance

In preterm infants, platelet transfusion, PC, and MPV were associated with mortality, and PC was also associated with any grade IVH and severe IVH. The findings suggest that a lower platelet transfusion threshold is preferred; however, the risk of a decreased PC should not be ignored.
Efficacy and Safety of Ketamine vs Electroconvulsive Therapy Among Patients With Major Depressive Episode
Authors: Rhee Taeho Greg , Shim Sung Ryul , Forester Brent P. , Nierenberg Andrew A. , McIntyre Roger S. , Papakostas George I. , Krystal John H. , Sanacora Gerard , Wilkinson Samuel T.
Published: October 2022

Importance

Whether ketamine is as effective as electroconvulsive therapy (ECT) among patients with major depressive episode remains unknown.

Objective

To systematically review and meta-analyze data about clinical efficacy and safety for ketamine and ECT in patients with major depressive episode.

Data Sources

PubMed, MEDLINE, Cochrane Library, and Embase were systematically searched using Medical Subject Headings (MeSH) terms and text keywords from database inception through April 19, 2022, with no language limits. Two authors also manually and independently searched all relevant studies in US and European clinical trial registries and Google Scholar.

Study Selection

Included were studies that involved (1) a diagnosis of depression using standardized diagnostic criteria, (2) intervention/comparator groups consisting of ECT and ketamine, and (3) depressive symptoms as an efficacy outcome using standardized measures.

Data Extraction and Synthesis

Data extraction was completed independently by 2 extractors and cross-checked for errors. Hedges g standardized mean differences (SMDs) were used for improvement in depressive symptoms. SMDs with corresponding 95% CIs were estimated using fixed- or random-effects models. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed.

Main Outcomes and Measures

Efficacy outcomes included depression severity, cognition, and memory performance. Safety outcomes included serious adverse events (eg, suicide attempts and deaths) and other adverse events.

Results

Six clinical trials comprising 340 patients (n = 162 for ECT and n = 178 for ketamine) were included in the review. Six of 6 studies enrolled patients who were eligible to receive ECT, 6 studies were conducted in inpatient settings, and 5 studies were randomized clinical trials. The overall pooled SMD for depression symptoms for ECT when compared with ketamine was −0.69 (95% CI, −0.89 to −0.48; Cochran Q, P = .15; I2 = 39%), suggesting an efficacy advantage for ECT compared with ketamine for depression severity. Significant differences were not observed between groups for studies that assessed cognition/memory or serious adverse events. Both ketamine and ECT had unique adverse effect profiles (ie, ketamine: lower risks for headache and muscle pain; ECT: lower risks for blurred vision, vertigo, diplopia/nystagmus, and transient dissociative/depersonalization symptoms). Limitations included low to moderate methodological quality and underpowered study designs.

Conclusions and Relevance

Findings from this systematic review and meta-analysis suggest that ECT may be superior to ketamine for improving depression severity in the acute phase, but treatment options should be individualized and patient-centered.
RNA m6Amethylation in cancer
Authors: Wang Zhaotong , Zhou Jiawang , Zhang Haisheng , Ge Lichen , Li Jiexin , Wang Hongsheng
Published: October 2022

N6‐methyladenosine (m6A) is one of the most abundant internal modifications in eukaryotic messenger RNAs (mRNAs) and non‐coding RNAs (ncRNAs). It is a reversible and dynamic RNA modification that has been observed in both internal coding segments and untranslated regions. Studies indicate that m6A modifications play important roles in translation, RNA splicing, export, degradation and ncRNA processing control. In this review, we focus on the profiles and biological functions of RNA m6A methylation on both mRNAs and ncRNAs. The dynamic modification of m6A and its potential roles in cancer development are discussed. Moreover, we discuss the possibility of m6A modifications serving as potential biomarkers for cancer diagnosis and targets for therapy.
A Totipotent “All‐In‐One” Peptide Sequentially Blocks Immune Checkpoint and Reverses the Immunosuppressive Tumor Microenvironment
Authors: Zhang Limin , Jiang Zhenqi , Yang Xi , Qian Yixia , Wang Minxuan , Wu Shang , Li Lingyun , Jia Fei , Wang Zihua , Hu Zhiyuan , Zhao Minzhi , Tang Xiaoying , Li Gang , Shang Hanbing , Chen Xiaoyuan , Wang Weizhi
Published: October 2022

Immune checkpoint blockade combined with reversal of the immunosuppressive tumor microenvironment (TME) can dramatically enhance anti‐tumor immunity, which can be achieved by using multiple‐agent therapy. However, the optimal dose and order of administration of different agents remain elusive. To address this dilemma, multiple agents are often grafted together to construct “all‐in‐one” totipotent drugs, but this usually comes at the cost of a lack of synergy between the agents. Herein, by comprehensively analyzing the conserved sites of the immune checkpoint and TME drug targets, peptide secondary structures, assembly properties, and other physicochemical properties, a high‐content peptide library is designed. By using the “3D‐molecular‐evolution” screening strategy, an efficient and totipotent “all‐in‐one” peptide (TAP) is obtained, which possesses the abilities of self‐assembling, blocking the PD‐1/PD‐L1 axis, inhibiting Rbm38‐eIF4E complex formation, and activating p53. It is shown that in mice treated with TAP, with either subcutaneous tumors or patient‐derived xenografts, PD‐L1 is blocked, with increased activation of both T and NK cells whilst reversing the immunosuppressive TME. Moreover, TAP can mitigate tumor activity and suppress tumor growth, showing superior therapeutic effect over antibody‐based drugs.
Solution‐Processed Gas Barriers with Glass‐Like Ultrahigh Barrier Performance
Authors: Sasaki Tatsuki , Sun Lina , Kurosawa Yu , Takahashi Tatsuhiro , Suzuri Yoshiyuki
Published: October 2022

Several electronic devices, such as perovskite solar cells (PSCs) and organic light‐emitting diodes (OLEDs), are very vulnerable to water vapor. Therefore, they require an ultrahigh‐performance gas barrier (water vapor transmission rate [WVTR]: less than 10−5 g m−2 d−1). The barrier performance of solution‐processed gas barriers is inferior to that of vacuum‐processed gas barriers; however, they possess advantages such as high resource efficiency, high throughput, low fabrication cost, and printability, which facilitate sustainable manufacturing and digital fabrication. The simultaneous realization of solution processability and ultrahigh barrier performance is highly desired. Herein, this work reports solution‐processed gas barriers developed using perhydropolysilazane (PHPS)‐derived SiN (PDSN) layers densified by vacuum ultraviolet (VUV) irradiation in a nitrogen atmosphere at room temperature. The appropriate PDSN thickness and irradiated VUV dose result in an excellent WVTR of 4.8 × 10−5 g m−2 d−1 (a barrier performance close to that of glass), which makes it among the best‐performing water vapor barriers recorded to date. The barrier performance is achieved with a thickness of only 990 nm and a short VUV irradiation time (2.4 min per PHPS layer). An ultrahigh‐performance barrier with rapid processability such as this expands the possibility of solution‐processed barrier technology.
New Coatings Systems with Improved Mechanical Properties by Combining Polymer Derived Ceramic and Physical Vapor Deposition Coating Methods
Authors: Wendel Jan‐Felix , Lenz Leite Mateus , Furtat Plinio , Tangermann‐Gerk Katja , Schafföner Stefan , Motz Günter
Published: October 2022

Different application methods for coatings have their individual advantages and disadvantages. Physical vapor deposition (PVD) titanium nitride coatings are hard but cannot be produced economically in high coating thicknesses, for example. Polymer derived ceramic (PDC) coatings, on the other hand, have good oxidation protection properties and can be easily produced with high thicknesses, but have worse mechanical properties. Therefore, a combination of different coating methods leads to a coating system providing the advantageous of both techniques. In this work, research on the combinability of a Durazane 2250 and a Durazane 1800 based PDC coating with a titanium nitride PVD coating is reported with focus on the mechanical properties of the combined system. It is shown that after complete ceramization of PDC coatings, a homogeneous and well adherent titanium nitride coating is achieved. The hardness (12.3 GPa) and scratch resistance (more than 10 N load at failure) as well as a reduction of affected area in cross‐cut tape test of 32% of the combined systems are obtained. The synergistic effect expected for the combined coating systems is demonstrated.
Plating of Ion‐Exchange Membranes: A Molecular Dynamics Study
Authors: Truszkowska Agnieszka , Boldini Alain , Porfiri Maurizio
Published: October 2022

Electroless plating of membranes offers a viable pathway to create flexible electrodes for soft sensors and actuators, as well as flexible electronics and batteries. Ionic polymer metal composites are a promising class of active materials, realized through electroless plating of ion‐exchange membranes. The plating and electrode‐membrane interface play a key role on their performance, but computational tools to inform the selection of the plating material and optimize the plating process are currently lacking. Here, this gap is filled through the study of the electrode‐membrane interface in different types of ion‐exchange membranes via molecular dynamics simulations. Both commercially available cation‐ and research‐grade anion‐exchange membranes are studied here. For platinum coating, it is predicted that cation‐exchange membranes will have a superior interface than anion‐exchange membranes, in terms of metal penetration into the membrane, reliability of actuation performance, and interface stability. The results are in line with previous endeavors documenting the higher stability of the interface for cation‐ than for anion‐exchange membranes, easier plating processes, and better electrochemical performance when working with cation‐exchange membranes. The proposed computational framework offers a versatile environment for testing different types of coatings for specific membranes, toward optimizing the performance of electrochemical devices with plated flexible electrodes.
Human Islet Amyloid Polypeptide (hIAPP) Protofibril‐Specific Antibodies for Detection and Treatment of Type 2 Diabetes
Authors: Bortoletto Angelina S. , Graham W. Vallen , Trout Gabriella , Bonito‐Oliva Alessandra , Kazmi Manija A. , Gong Jing , Weyburne Emily , Houser Brandy L. , Sakmar Thomas P. , Parchem Ronald J.
Published: October 2022

Type 2 diabetes mellitus (T2D) is a major public health concern and is characterized by sustained hyperglycemia due to insulin resistance and destruction of insulin‐producing β cells. One pathological hallmark of T2D is the toxic accumulation of human islet amyloid polypeptide (hIAPP) aggregates. Monomeric hIAPP is a hormone normally co‐secreted with insulin. However, increased levels of hIAPP in prediabetic and diabetic patients can lead to the formation of hIAPP protofibrils, which are toxic to β cells. Current therapies fail to address hIAPP aggregation and current screening modalities do not detect it. Using a stabilizing capping protein, monoclonal antibodies (mAbs) can be developed against a previously nonisolatable form of hIAPP protofibrils, which are protofibril specific and do not engage monomeric hIAPP. Shown here are two candidate mAbs that can detect hIAPP protofibrils in serum and hIAPP deposits in pancreatic islets in a mouse model of rapidly progressing T2D. Treatment of diabetic mice with the mAbs delays disease progression and dramatically increases overall survival. These results demonstrate the potential for using novel hIAPP protofibril‐specific mAbs as a diagnostic screening tool for early detection of T2D, as well as therapeutically to preserve β cell function and target one of the underlying pathological mechanisms of T2D.
A Germline‐Specific Regulator of Mitochondrial Fusion is Required for Maintenance and Differentiation of Germline Stem and Progenitor Cells
Authors: Zhang Ru , Tu Yi‐Xuan , Ye Ding , Gu Zhenglong , Chen Zhen‐Xia , Sun Yonghua
Published: October 2022

Maintenance and differentiation of germline stem and progenitor cells (GSPCs) is important for sexual reproduction. Here, the authors identify zebrafish pld6 as a novel germline‐specific gene by cross‐analyzing different RNA sequencing results, and find that pld6 knockout mutants develop exclusively into infertile males. In pld6 mutants, GSPCs fail to differentiate and undergo apoptosis, leading to masculinization and infertility. Mitochondrial fusion in pld6‐depleted GSPCs is severely impaired, and the mutants exhibit defects in piRNA biogenesis and transposon suppression. Overall, this work uncovers zebrafish Pld6 as a novel germline‐specific regulator of mitochondrial fusion, and highlights its essential role in the maintenance and differentiation of GSPCs as well as gonadal development and gametogenesis.
Transparent and Multi‐Foldable Nanocellulose Paper Microsupercapacitors
Authors: Kim Sang‐Woo , Lee Kwon‐Hyung , Lee Yong‐Hyeok , Youe Won‐Jae , Gwon Jae‐Gyoung , Lee Sang‐Young
Published: October 2022

Despite the ever‐increasing demand for transparent power sources in wireless optoelectronics, most of them have still relied on synthetic chemicals, thus limiting their versatile applications. Here, a class of transparent nanocellulose paper microsupercapacitors (TNP‐MSCs) as a beyond‐synthetic‐material strategy is demonstrated. Onto semi‐interpenetrating polymer network‐structured, thiol‐modified transparent nanocellulose paper, a thin layer of silver nanowire and a conducting polymer (chosen as a pseudocapacitive electrode material) are consecutively introduced through microscale‐patterned masks (which are fabricated by electrohydrodynamic jet printing) to produce a transparent conductive electrode (TNP‐TCE) with planar interdigitated structure. This TNP‐TCE, in combination with solid‐state gel electrolytes, enables on‐demand (in‐series/in‐parallel) cell configurations in a single body of TNP‐MSC. Driven by this structural uniqueness and scalable microfabrication, the TNP‐MSC exhibits improvements in optical transparency (T = 85%), areal capacitance (0.24 mF cm−2), controllable voltage (7.2 V per cell), and mechanical flexibility (origami airplane), which exceed those of previously reported transparent MSCs based on synthetic chemicals.
3D Auxetic Metamaterials with Elastically‐Stable Continuous Phase Transition
Authors: Wang Lianchao , Ulliac Gwenn , Wang Bing , Iglesias Martínez Julio A. , Dudek Krzysztof K. , Laude Vincent , Kadic Muamer
Published: October 2022

In solid state physics, phase transitions can influence material functionality and alter their properties. In mechanical metamaterials, structural‐phase transitions can be achieved through instability or buckling of certain structural elements. However, these fast transitions in one mechanical parameter typically affect significantly the remaining parameters, hence, limiting their applications. Here, this limitation is addressed by designing a novel 3D mechanical metamaterial that is capable of undergoing a phase transition from positive to negative Poisson's ratio under compression, without significant degradation of Young's modulus (i.e. the phase transition is elastically‐stable). The metamaterial is fabricated by two‐photon lithography at the micro‐scale and its mechanical behavior is assessed experimentally. For another choice of structural parameters, it is then shown that the auxetic behavior of the considered 3D metamaterial class can be maintained over a wide range of applied compressive strain.
Protons: Critical Species for Resistive Switching in Interface‐Type Memristors
Authors: Kunwar Sundar , Somodi Chase Bennett , Lalk Rebecca A. , Rutherford Bethany X. , Corey Zachary , Roy Pinku , Zhang Di , Hellenbrand Markus , Xiao Ming , MacManus‐Driscoll Judith L. , Jia Quanxi , Wang Haiyan , Joshua Yang J. , Nie Wanyi , Chen Aiping
Published: October 2022

Interface‐type (IT) resistive switching (RS) memories are promising for next generation memory and computing technologies owing to the filament‐free switching, high on/off ratio, low power consumption, and low spatial variability. Although the switching mechanisms of memristors have been widely studied in filament‐type devices, they are largely unknown in IT memristors. In this work, using the simple Au/Nb:SrTiO3 (Nb:STO) as a model Schottky system, it is identified that protons from moisture are key element in determining the RS characteristics in IT memristors. The Au/Nb:STO devices show typical Schottky interface controlled current–voltage (I–V) curves with a large on/off ratio under ambient conditions. Surprisingly, in a controlled environment without protons/moisture, the large I–V hysteresis collapses with the disappearance of a high resistance state (HRS) and the Schottky barrier. Once the devices are re‐exposed to a humid environment, the typical large I–V hysteresis can be recovered within hours as the HRS and Schottky interface are restored. The RS mechanism in Au/Nb:STO is attributed to the Schottky barrier modulation by a proton assisted electron trapping and detrapping process. This work highlights the important role of protons/moisture in the RS properties of IT memristors and provides fundamental insight for switching mechanisms in metal oxides‐based memory devices.
High‐Performance and Environmentally Robust Multilevel Lead‐Free Organotin Halide Perovskite Memristors
Authors: Liu Zehen , Tang Hao , Cheng Pengpeng , Kang Ruyan , Zhou Jian , Zhao Xian , Zhao Jia , Zuo Zhiyuan
Published: October 2022

With a striking explosion of digital information, organic–inorganic halide perovskite (OHP) memristors have been regarded as a promising solution to break the von Neumann bottleneck as the nonvolatile computing‐in‐memory architecture. However, toxicity and stability under ambient conditions are two critical issues for practical applications. Here, lead‐free MASnI3 (MASI) perovskites are reported with improved resistive switching (RS) performance via defects passivating by introducing PEACl. In‐Sn/PEACl‐MASI/PEDOT:PSS/ITO memristor arrays (10 × 10) exhibit reproducible RS with low SET/RESET voltage (VSET/VRESET, +0.58/−0.49 V), ultrahigh ON/OFF ratio (8.5 × 103), stable endurance (2 × 103 cycles), excellent retention (2 × 104 s), high device yield (88%), and multilevel storage. RS remains robust in harsh environments, including high temperature and humidity, long‐term light irradiation, and open‐air conditions. Importantly, a complete physical simulation model that quantitatively and accurately describes RS in vacancy concentration, temperature, and electric potential is proposed originating from conductive filaments formation/rupture. Additionally, PEACl‐MASI memristors are successfully fabricated on polyethylene terephthalate (PET) and Si substrates to explore the potential for large‐scale application on different substrates. The PEACl‐MASI memristors provide an opportunity to develop the next generation of high‐performance and environmentally robust multilevel information storage devices.