bluuebunny/crossref_metadata_2025 huggingface dataset:
IN SILICO SCREENING OF MAJOR CANCER DRUG TARGETS (GROWTH FACTOR RECEPTORS) FOR NATURE DERIVED PHYTOCHEMICALS
Authors: Trivedi Tithi , Kumar Siva , Mankad Archana , Patel Saumya , Rawal Rakesh , Pandya Himanshu
Published: October 2022

Cancer i s a group of abn ormal cells. The unregulated gro wth factor recepto r t yrosin e kinase ( GFR- TK) proteins are implicated in  the  proliferation o f mo re  than  60 % o f all can cer t ypes. Screenin g o f ph ytoch emicals for their anti - angiogenic potential has b een a gro wing area o f research in the mod ern d ecad e. There i s a well - kno wn principle that natural co mpounds are active against several diseases, includin g variou s t yp es of can cer. Th e present research work fo cuses on kno wn gro wth factor receptors  ( GFRs)  as an important  target  fo r co mputation al   s tudies.  In   this   stud y,   96   curated  anti - can cer co mpounds were virtu ally screened against the EGFR, FGFR, IGFR, and HGFR usin g molecular dockin g so ftware. For each GFR, we h ave considered ten top most results as potential hits. Among them, co mmon f i ve results are: Spiro solan e, Ginkgetin, Fangchinoline, Theaflavin and Ursolic acid. These co mpounds have b een reported to show antican cer activities in the l i t erature. With the help of different interaction analysis tools, the protein - l i gand inter action patterns between th e functional groups o f these co mpounds were analyzed. Hydro gen bonding and h ydrophobic forces are th e main co mponents o f th e interactions o f th ese hits, similar to those exp erimental fo r th e kno wn inhibitors. Fro m the maximu m nu mb ers o f hits, i t could be indicated that co mpounds  Spirosolan e, Ginkgetin, Fan gchinoline, Th eaflavin and Ursolic acid are pro miscuous l ead s in the drug disco very process.
BILATERAL RELATIONSHIP BETWEEN TOURISM AND CLIMATE CHANGE: IMPACTS, VULNERABILITY & SOLUTIONS
Authors: Singh Ankita , Bhatt Pathik , Modi Nainesh
Published: October 2022

Human activities are directly or indirectly assigned to “Climate change”. Global scenario indicates that changing climate is an influencing phenomenon with wide range of impacts on different levels in societies and industries. In current scenario tourism industry is considered as one of the fastest-growing industries with direct relation to changing climate. Tourism is totally dependent on various climatic conditions over specific destinations. Any effort to separate them will lead to danger. Tourism is one of the fastest-growing industries which is also responsible for excess amount of emissions and also includes large scope to adapt or mitigate changing climate. Tourism has the capability to create beneficial effects on the environment by contributing to environmental protection and conservation. It is a way to raise awareness of environmental values and it can serve as a tool for foreign investments. As tourism is a growing sector it is essential to identify its promising impacts on climate change. With marked increase in tourism industry it is quite easy to understand the flow of tourist by statistical analysis of secondary data, and its relative possible impacts. Lack of research in sustainable tourism and climate change provides us platform to built bilateral approach for solutions using micro observations of destination as well as generation of primary data using socio-economic methods. This approach for sustainable tourism and its advantages play a major role in global context. Tourism, a highly growing industry is also providing various possibilities to achieve sustainable development goals (SDGs) and to stabilize the global threat of 21st century.
Plataformas virtuales educativas y aprendizaje colaborativo en estudiantes de una universidad pública, de Lima, Perú
Authors: Erazo Moreno Milagros Maria , Guizado Oscco Felipe , Huachara Martínez Enith , Nina-Cuchillo Josue , Nina-Cuchillo Enoc Eusebio
Published: October 2022

Las plataformas virtuales educativas se hicieron necesarias durante el periodo de pandemia, para brindar clases a distancia en las instituciones de educación superior. En su uso, se pudo observar el desempeño de los estudiantes en la construcción de conocimientos, mediante el aprendizaje colaborativo. Bajo este contexto, la finalidad de la investigación fue determinar la relación entre el uso de las plataformas virtuales educativas y el aprendizaje colaborativo, en estudiantes de una universidad pública, en Lima, Perú. Para ello, se realizó una metodología de tipo básica, con nivel correlacional descriptivo, diseño no experimental y corte transeccional. En cuanto a la muestra fueron 150 alumnos de la Facultad de Educación, a quienes, mediante la técnica de la encuesta, se le aplicó dos cuestionarios para medir la percepción sobre las variables. Se tuvo como resultados que, el uso de las plataformas virtuales educativas fue deficiente y el aprendizaje colaborativo de los estudiantes alcanzó un nivel bajo. Además, se concluyó que existe relación directa entre dichas variables, siendo la correlación positiva y elevada (Rho de Spearman=0,892).
Character Education, Learning Models, Blended Learning
Authors: Marlina Tuti
Published: October 2022

Pandemi memaksa kalangan pendidik untuk beradaptasi dengan kebiasaan baru dalam melaksanakan proses pembelajaran. Pembelajaran yang semula hanya tatap muka berubah menjadi daring. Hal inilah yang kemudian memunculkan berbagai problem sehingga perlu menerapkan pembelajaran campuran (blended learning). Agar pendidikan sesuai dengan tujuannya, maka dalam proses pembelajaran perlu menanamkan pendidikan karakter. Tujuan penelitian ini adalah untuk membangun sebuah konsep pendidikan karakter berbasis model blended learning. Metode penelitian yang digunakan adalah kualitatif studi literatur dengan hasilnya berbentuk konseptual. Hasil dari penelitian ini menunjukkan bahwa pelaksanaan pendidikan karakter berbasis model blended learning dilakukan dengan cara memodifikasi perangkat pembelajaran (silabus dan RPP) menjadi berbasis karakter. Adapun dalam pelaksanaan pembelajarannya guru perlu mengimplementasikan berbagai teknik mengajar, metode dan media pembelajaran berbasis karakter dan dilaksanakan secara kombinasi (daring-luring). Adapun teknik mengajar yang dimaksud adalah Live Event (Pembelajaran Tatap Muka), Self-Paced Learning (Pembelajaran Mandiri), Collaboration (Kolaborasi), Assessment (Penilaian Atau Pengukuran Hasil Belajar), Performance Support Materials (Dukungan Bahan Belajar), Menyaring Informasi Penting dari Internet. Sedangkan pada metode pembelajaran terdiri dari: Live In, Keteladanan, Keaktifan Siswa (Inquiry Learning), Pencarian Bersama (Information Search), Penemuan (Discovery Learning). Serta media pembelajaran yang terdiri dari perangkat lunak (Web, Video Streaming, Audio dan Media Sosial) dan perangkat keras (CD, Smartphone, Komputer, Laptop, LCD, Alat Praktikum, dll).
Mahadevi Verma Ke Sansmarnatamak Rekhachitron Mein Dalit Savedna
Authors: डॉ रविन्द्र कुमार
Published: October 2022

हिन्दी साहित्य में दलित- साहित्य की सुदीर्घ परंपरा है। मानव को केन्द्रबिन्दु बनाकर बहिष्कृत समाज की वेदना को वाणी प्रदान करने वाले इस साहित्य की मुख्य विधा प्रारंभ में आत्मकथा थी, जो अनुभूत यथार्थ पर आधारित होती है। कालांतर में साहित्य की अन्य विधाओं सहित रेखाचित्र और संस्मरण में भी दलित-वेदना को अभिव्यक्ति मिली। यथार्थ पर आधारित इन विधाओं में कल्पना की जगह सत्य की समग्रता तथा लेखक की अनुभूतियों, स्मृतियों और जीवन-मूल्यों का अद्भुत संगम होता है। महादेवी वर्मा हिन्दी की सर्वोत्तम संस्मरण लेखिका और रेखाचित्रकार हैं। इनके ग्यारह संस्मरणात्मक रेखाचित्रों का संग्रह “अतीत के चलचित्र' 94। में प्रकाशित हुआ, जिनमें आठ रेखाचित्र दलित वर्ग का प्रतिनिधित्व करते हैं। 943 में प्रकाशित, द्विवेदी-पदक से सम्मानित “स्मृति की रेखाएँ' के सात रेखातित्रों में पाँच दलित वर्ग को समर्पित हैं। अन्य रेखाचित्र भी किसी न किसी रूप में समाज से बहिष्कृत और उपेक्षित चरित्रों के ही प्रतिरूप हैं। इन संस्मरणात्मक रेखाचित्रों के सभी पात्र दीन, विवश परंतु कर्मठ और रचनाशील हैं। पुरूष-पात्रों में दृढ़ता, उत्साहपूर्ण शक्ति तथा आत्म-गौरव है, तो स्त्री-पात्रों में गरिमामयी बनानेवाली भावनात्मक दुबर्लता। अपने जीवन से जुड़े इन चित्रों के व्यक्तित्व के सकारात्मक पक्षों पर विशेष बल देते हुए महादेवी जी ने अनेक सामाजिक विकृतियों की चर्चा की और इन्हें हर संभव मदद देकर समाज-सुधार की दिशा में सार्थक पहल भी की। वास्तविक जीवन पर आधारित होने के कारण ये रेखाचित्र जीवन के अनेक रंग तो प्रस्तुत करते ही हैं, महादेवी जी की गहरी संवेदना के प्रतीक भी हैं। इनमें यदि जीवन का स्पंदन और आत्मा का वृहत्कंपन है तो अछूतोद्वार का संदेश भी है।
Shahjahanpur Jile Ke gramin Vikas Mein Swrojgaar Yojnao Ka Pravhaw- Ek Arthik Vishleshan
Authors: डॉ पुष्पेन्द्र
Published: October 2022

शाहजहाँपुर जिले में बेरोजगारी को दूर करने हेतु एवं इसके समाधान हेतु कई  स्वरोजगार  योजनाएँ  शासन  द्वारा  चलाई  जा  रहीं  हैं,  शिक्षित बेरोजगारी को दूर करने हेतु सभी वर्गों के युवाओं के लिए शासन द्वारा प्रधानमंत्री रोजगार योजना चलाई जा रही है। यह योजना जिले में, जिला व्यापार एवं उद्योग केन्द्र द्वारा संचालित की जा रही है। कई वर्षों से यह योजना जिले की बैंकिंग  व्यवस्था  पर  विपरीत  प्रभाव  डाल  रही  है।  इसका  कारण योजना के तहत् ऋण प्राप्त करने के पश्चात् हितग्राहियों द्वारा ऋणों का पुनर्भुगतान नहीं किया जाना है। योजनान्तर्गत  प्रशिक्षण  कार्यक्रम  में  विषय-विशेषज्ञ  के  रूप  में स्थानीय प्रसिद्व व्यापारियों एवं उद्योगपतियों को आमंत्रित किया जाए तथा बाजार प्रबंधन के संदर्भ में विस्तृत जानकारी पशिणार्थियों को विशेष रूप से दिलाई जाए। शासन को औपचारिक शिक्षा संस्थाओं के स्थान पर रोजगार-मूलक प्रशिक्षण केन्द्र स्थापित करने पर बल देना  चाहिए। योजनाओं  के  प्रभावी क्रियान्वयन हेतु प्रशासनिक संगठनों में कर्मचारियों की संख्या बढ़ाई जानी चाहिए। उन्हें प्रेरणा प्रदान करने के लिए विभिन्न प्रेरक उपाय किए  जाने  चाहिए।  योजनांतर्गत  प्रशिक्षण  हेतु  एक  सुसंगत  माॅडल तैयार  किया जाना  चाहिए।  योजना  क्रियान्वयन  के  प्रत्येक  स्तर  पर हितग्राहियों एवं कार्यक्रम अधिकारियों दोनों को प्रशिक्षित किया जाना चाहिए।
EFFECT OF MALATHION ON THE HISTOLOGY OF KIDNEY OF HETEROPNEUSTES FOSSILIS
Authors: RAMESH CHANDRA  , DHERMENDRA
Published: October 2022

In recent years it has become a normal practice to test all new chemicals for the toxicity before they could reach consumers. Major purpose of the toxicological investigations to provide a basis for estimating the maximum dose that may be tolerated by animals throughout their life time without manifesting any adverse effect In the present study, shrinker tubules were found in malathion treated kidney and dilated nuclei of tubules were seen in malathion treatment. Again, chlorpyrifos resulted in elongation of renal tubules.
Gramin Avam Samajik Chetna mein Fadishwarnath Renu Ka Hindi Khani Sahitya
Authors: Dr Mahendra Singh
Published: October 2022

फणीश्वरनाथ रेणु की प्रसिद्धि ग्रामकथा-लेखन और यथार्थवादी से हुआ है। फणीश्वरनाथ रेणु को विशेषतः मैला आँचल' और 'परती परिकथा के रूप में याद किया जाता है जबकि रेणु जी ने पाँच दर्जन से अधिक कहानियों की भी रचना की है। रेणु की पहली औपन्यासिक कृति मैला आँचल का प्रकाशन में हुआ। उसे गोदान के बाद का दूसरा महाकाव्यात्मक उपन्यास माना गया।'रेणु' के आशावान मन शैक्षणिक प्रगति से गांव की सामूहिक प्रगति का सपना देखता है, जातीयता का टूटन चाहता बहुत कुछ बदलाव आता भी है। गांव के नवयुवक और स्त्रियां जितेन्द्र की हवेली में आने लगती है। नवयुवक सुवंश- मलारी के प्रेम संबंधों को लेकर उठे वितंडावाद में उसका साथ देते हैं। शिक्षा औद्योगीकरण एवं आधुनिकीकरण गांव को नयी मानसिकता प्रदान करते है। अंधविश्वासों के जड़बद्धता संस्कार अब हिलने लगे हैं। रेणु को ग्राम परिवेश का समग्र बोध है। उन्हें उसके यथार्थ की गहरी परख और पहचान है जिसे वे लोक तत्वों की समाहिति से और भी गहरा चित्रित करते हैं। इस चित्रण में 'रेणु' विभिन्न बारीकियों, अनेक कोणों एवं विविध आयामों से परिवेश की जीवन्त सृष्टि करते हैं।
Collection Management in Libraries of Rohilkhand Region
Authors: Singh Dr.Niraj
Published: October 2022

The amount of valuable electronic resources that may be included in a library's collection is expanding at an exponential rate, which presents a challenge for librarians.’ (Maheswarappa) Several methods and related standards have been established in recent years that enable the creation and distribution of documents in electronic form. The procedure involves selecting and de-selecting present-day and historical resources, planning acquisition and preservation methods, and assessing collections to ascertain how effectively they meet operator requirements. The construction of collections is now more difficult than ever in an increasingly digitized age.
Sustainable Technology and its Role in Business Innovation
Authors: Singh Pankaj
Published: October 2022

Innovation and sustainable technology are becoming more and more intertwined. Indeed, innovative, cutting-edge technology can significantly reduce environmental burdens, enhance social circumstances, and foster economic progress. However, there are gaps in the research about what motivates the creation of "sustainable" technical breakthroughs, what fosters their expansion, and what motivates organizations to adopt "sustainable" technological innovations. The design and analysis of intricate, integrated management systems as well as sustainable development are frequently linked to sustainable technology, which is a key area of study for environmental science and the advancement of the world economy. Waste minimization and reduced material and energy input are the most important environmental objectives. The current study looks at the connection between innovation and environmentally friendly technology.
Collection Management in Libraries of Rohilkhand Region
Authors: Singh Neeraj Kumar
Published: October 2022

The amount of valuable electronic resources that may be included in a library's collection is expanding at an exponential rate, which presents a challenge for librarians.’ (Maheswarappa) Several methods and related standards have been established in recent years that enable the creation and distribution of documents in electronic form. The procedure involves selecting and de-selecting present-day and historical resources, planning acquisition and preservation methods, and assessing collections to ascertain how effectively they meet operator requirements. The construction of collections is now more difficult than ever in an increasingly digitized age.
Swami Nem Pal’s India Malcontent
Authors: Singh Vinai Kumar
Published: October 2022

The long poem "India Malcontent" was written by Swami Nem Pal Singh, a powerful and insightful poet from Dist Bulandshahahr. It is a compilation of fragmented stanzas that offers a glimpse inside the poet's mind. The written lines are the words of a soul that is aware of both the inner and outward worlds. The author's creation is the outcome of wandering political musings. He may have aspirations to build a godly kingdom in our nation. This little volume's "Dedication" to the courageous and greatest of this nation shows Swami's unshakable devotion to India. The constant erosion of moral values in the society fixates the poet and he lashes at the moral turpitude rampant all over the breath and length of India. His poetry appears to spring from the depth of his heart, hence he tickles the heart of the readers. 'India Malcontent' betrayed poetic insights and high flight of imagination. 'India Malcontent' is Swami Nem Pal's tribute to the brave and best of this country. He has perhaps a dream of establishing a divine kingdom in our country. The paper is a modest attempt to analyse the various major feature of the maiden collection of the poet.
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Authors: Zilberman Mark
Published: October 2022

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Will State of Happiness Assure Global Peace?
Authors: Aribe Jr. Sales , Panes Joan Marie
Published: October 2022

This research sought to determine the commonalities between countries with high levels of of happiness but low global state of peace. The values used were from published indices, namely, State of Global Happiness and Global Peace Index. These were analysed using nominal logistic regression in order to find the relationship between these variables. The general trend is that happy countries are peaceful countries. However, several countries did not fit this finding, namely: Israel, Mexico, Saudi Arabia, Colombia, Bahrain, Russia, Libya, Philippines, Turkey and Pakistan. Indicators used in the State of Global Happiness and Global Peace Index were further analysed. Findings suggest that individuals in these countries have strong social support that enables them to consider themselves happy despite the low state of peace in their respective countries, the factors of which vary from region to region and country to country.
Cornelia de Lange Syndrome: A Case Report with a Novel Congenital Heart Disease Association
Authors: Allugmani Mohammad D. , El-Harbi Mazen K. , Khoshhal Mohammad S. , Alrabghy Najia , Almutery Sabreen , Alawfi Abdulsalam D. , Abo-Haded Hany M.
Published: October 2022

Introduction: Cornelia de Lange syndrome (CdLS) is a rare non-hereditary syndrome. The key diagnosis is unique facial features, limb anomalies, and growth retardation. Cardiac defects with gastrointestinal and genitourinary anomalies may be associated. Case Presentation: This is a case of neonatal CdLS that we think is interesting due to its association with a novel congenital heart complex. Conclusions: Patients with CdLS have a high incidence of congenital heart disease (CHD), so a cardiologic study of all of these patients is suggested.
Evaluation of Clinicopathologic Factors and Surgery Management on Borderline Ovarian Tumor Outcomes
Authors: Shiravani Zahra , Namazi Niloofar , Hashemi Masooumeh , Najib Fateme Sadat , Hajisafari Tafti Mojgan
Published: October 2022

Background: Borderline ovarian tumor (BOT) is a tumor most prevalent in young woman with desire to fertility. There are some controversies on the patient characteristic besides to the factors affecting the recurrence rate among different races. Objectives: The aim of this study is to evaluate clinicopathologic features of the tumor to discover the controversies on the topic. Methods: Medical data of the all referred patients to Motahari clinic from January 2010 till October 2020 were recorded. Patient clinicopathologic characteristics affecting on outcome were evaluated. By using SPSS software, data were tested by chi-square and fish exact test. Also, log rank test was used for survival analysis Results: Totally 145 patients were enrolled. 61.4% versus 38.6% of the patients underwent fertility sparing surgery and radical surgery respectively with common characteristics of mostly belong to stage 1A disease (61.8% vs. 66.1%), unilateral (93.3% vs. 89.3%), serous histology (51.7% vs. 66.1%). The characteristics were different in the aspects of age and tumor size. In the aspect of recurrence rate, higher FIGO stage, younger age, tumor size less than 10cm, performing laparoscopy and fertility sparing surgery were with higher rate of recurrence (P-value < 0.05) while histology type of the tumor, lateralization, micropapillary, microinvasion, noninvasive peritoneal implants, receiving adjuvant chemotherapy and performing lymphadenectomy were not statistically significant for recurrence (P-value > 0.05). Two patients had malignant transformation. Conclusions: Fertility sparing surgery was with more recurrence rate in borderline ovarian tumor patients. However, micropapillary, microinvasion were not significantly with higher recurrence rate in our study but they are challenging issues in border line ovarian tumors among different studies. Due to most prevalence of border line ovarian tumors in young women and desire of fertility preservation, we should notice more to clinicopathologic and surgery types affecting on recurrence of BOTs.
Comparing the COVID-19 Mortality Rate in Cancer Patients with and Without a History of Chemotherapy
Authors: Bazgir Nasrin , Taghinezhad Fakhredin , Nourmohammadi Hassan , Azami Golnaz , Ahmadi Iraj , Mozafari Aliashraf
Published: October 2022

Background: Patients with cancer are potentially vulnerable to COVID-19 infection due to the immune-compromised state of cancer or its treatment complications. Objectives: This study compared the COVID-19 mortality rate in cancer patients with and without a history of chemotherapy. Methods: This registry-based cohort study launched from March 2020 to March 2021 contains 2350 records in which 64 COVID-19 patients with cancer were included, of which 27 patients underwent the chemotherapy plan within eight weeks before confirmed COVID-19. In addition, age and sex were matched in patients without a history of cancer as a control group. Two groups of cancer patients with and without a history of chemotherapy compared to the control group using cox proportional hazard regression models in Stata.10 software. Results: Patients with cancer had a higher hazard for in-hospital mortality from COVID-19 infection (adjusted HR; 2.27, 95% CI: 1.25 - 4.13, P = 0.007) after adjusting for age, sex, body mass index (BMI), and co-morbidities. Our result showed no significant association between chemotherapy and control groups (adjusted HR; 1.65, 95% CI: 0.60 - 4.56, P = 0.33). Conclusions: Patients with cancer faced a risk of mortality from COVID-19 two times higher than those without cancer. However, chemotherapy did not increase the mortality following COVID-19 infection.
Spironolactone Induces Apoptotic Cell Death in Human Glioblastoma U87-MG Cancer Cells
Authors: Mohammadi Zeinab , Mostakhdem Hashemi Mohammad , Saghaeian Jazi Marie
Published: October 2022

Background: Spironolactone is a conventional drug widely in use for the treatment of heart failure and hypertension patients. On the other side recent studies have reported spironolactone can prevent growth and drug resistance in cancer stem cells (CSCs), by inhibiting DNA double-strand break (DSB) repair; suggesting its potential application in cancer therapy. Objectives: Our study aimed at assessing the potential cytotoxicity of spironolactone in human U87-MG glioblastoma cells. Methods: Different concentrations of spironolactone (0 - 50 μM) for 48 and 72 h were used for treatment. Cell viability assay was carried out by the 4, 5-dimethylthiazole-2-yl, 2, 5-diphenyl tetrazolium (MTT) method. Apoptosis was evaluated using annexin V/PI staining and flow cytometry and colorimetric measurement of caspase 8 and 9 activity. Results: Our findings showed a significant dose-dependent cytotoxic effect of spironolactone with maximum effect in 30 μM (P-value < 0.05). Spironolactone can induce approximately 20% apoptotic cell death in U87-MG cancer cells which were mainly related to early apoptotic cells. Indeed, the activity of caspase 8 and 9 was significantly elevated in spironolactone-treated cells compared to mock control. Conclusions: Findings showed the cytotoxic effect of spironolactone in U87-MG glioblastoma cancer cells in a mechanism dependent on apoptosis cell death induction. Our findings suggest the potential application of spironolactone in the treatment of glioblastoma in vitro.
Investigation of Resilience in Patients with Epilepsy Referred to Medical Centers in Isfahan in 2021
Authors: Motioleslami Moein , Fereidooni-Moghadam Malek , Yazdannik Ahmadreza , Etemadifar Masoud
Published: October 2022

Background: Epilepsy is a worldwide common neurological disorder characterized by an enduring predisposition to epileptic seizures. Protective elements are circumstances that help an individual cope with stressful events more effectively. Resilience may act as a protective factor against the subjective experience of hardship, especially when receiving a probable negative medical diagnosis. Objectives: The purpose of this study was to explore resilience among patients with epilepsy. Methods: This descriptive-analytical study was performed in 2021 on 250 patients with epilepsy referred to selected medical centers in Isfahan, who were selected by the simple random sampling method. Data collection tools included a demographic information questionnaire and Connor- Davidson Resilience Scale (CD-RISC). Data were analyzed in SPSS software version 26 using descriptive statistics such as the mean and standard deviation for quantitative variables and frequency and percentage for qualitative variables. Stepwise regression tests were used to examine the relationship between independent variables and dependent variables while controlling contextual and confounding variables. Results: In this study, the mean (standard deviation) of the resilience score in epileptic patients was 60.34 ± 19.86. The socioeconomic status and the level of education, but not martial status and gender, were found to correlate significantly with resilience (P = 0.445 and P = 0.396, respectively). Duration of epilepsy, age, and job status inversely correlated with resilience (P = -0.269, P = -0.131, P = -0.155, respectively). Conclusions: According to the results of this study, increasing knowledge and understanding of the relationship between epilepsy and resilience may help obviate this problem in patients with epilepsy.
Comparing the Effect of High-intensity and Low-intensity Transcutaneous Electrical Nerve Stimulation on Pain Relief and Functional Activity Improvement in Patients with Knee Osteoarthritis
Authors: Delkhoush Cyrus Taghizadeh , Binaei Fatemeh , Pakdaman Mohsen , Oskoie Mohamad
Published: October 2022

Background: Osteoarthritis is a common musculoskeletal disorder in elderly people, and the most common form appears in the knee joint. These patients suffer from pain, joint stiffness, and problems with functional activities. So, it is essential to offer a proper treatment plan for these patients. Objectives: The goal of this research is to compare the effect of high- and low-intensity transcutaneous electrical nerve stimulation (TENS) therapy on reducing pain and improvement of functional activity. Methods: Using simple randomization method, a total of 36 patients were divided into two groups receiving high- and low-intensity TENS therapy. All patients received ten sessions of physiotherapy (three sessions per week). Pain and functional activities were measured and compared before and after the study. Results: Although there was a significant difference between the two groups in pain index (P < 0.05), no difference in functional activity was observed between the two groups. Conclusions: Using both high- and low-intensity techniques can be effective in reducing the pain and improving the knee joint function. However, pain decreased more significantly in the high-intensity group compared to low-intensity group.
EPA Takes Action Against Harmful “Forever Chemicals” in the US Water Supply
Authors: Suran Melissa
Published: October 2022

This Medical News article discusses new EPA advisories for a class of synthetic chemical compounds known as PFAS, which are ubiquitous in the environment and in humans, as well as new National Academies guidance on expanded testing for exposure.
Predicting DRESS Syndrome Recurrence—The ReDRESS Score
Authors: Sharma Ajay N. , Murphy Kenneth , Shwe Samantha , Miller Melanie , Mesinkovska Natasha A. , Rojek Nathan W. , Worswick Scott
Published: October 2022

This cross-sectional study of DRESS syndrome cases creates a model capable of predicting recurrence to identify patients most at risk.
Estimated Clinical Trial Capacity of Sites Participating in the COVID-19 Convalescent Plasma Expanded Access Program
Authors: Gustafson M. Sage , Patel Aman , Hong Chuan , Meline Miles , Peña Daniella , Tang Charis , Fernandez Lynch Holly
Published: October 2022

This cross-sectional study estimates the trial capacity of sites participating in the COVID-19 convalescent plasma expanded access program.
Defining Essential Surgery in the US During the COVID-19 Pandemic Response
Authors: Mattingly Aviva S. , Eddington Hyrum S. , Rose Liam , Morris Arden M. , Trickey Amber W. , Cullen Mark R. , Wren Sherry M.
Published: October 2022

This cohort study compares the volume of performed surgical procedures classified as essential, urgent, and nonurgent before and after elective surgeries were restricted during the COVID-19 pandemic in the US.
Impact of the National Amyotrophic Lateral Sclerosis Registry: Analysis of Registry‐funded Research
Authors: Rechtman Lindsay , Brenner Stephan , Wright Marcienne , Ritsick Maggie , Rahman Farhana , Han Moon , Raymond Jaime , Larson Theodore , Horton D. Kevin , Mehta Paul
Published: October 2022

Objective

This research aims to examine the impact of the National Amyotrophic Lateral Sclerosis (ALS) Registry‐funded research activities.

Methods

Registry‐funded research and related publications were identified through the National ALS Registry website, the National Institutes of Health (NIH) Reporter website, and verified by Principal Investigators. Key study characteristics (e.g., study population, sample size) and key impact features (e.g., risk factors) were abstracted and recorded on study abstraction forms. Descriptive statistics were used to analyze the volume, productivity, and findings of the Registry‐funded research.

Results

Since 2012, the National ALS Registry funded 21 research projects. Of these, 14 were through extramural research grants and included in the analysis. These studies are often related to environmental, medical conditions, and genetic risk factors. On average, the funded grants produced 1 to 2 publications which were cited 114 times by other researchers. The relative citation ratio averaged 1.81 with a weighted relative citation ratio of 16.28. These studies supported the identification and confirmation of candidate risk factors. Environmental and occupational risk factors typically related to heavy metal exposure (e.g., lead, mercury) and agricultural chemicals (e.g., pesticides, herbicides), and the occupations associated with exposure to these substances were most frequently explored.

Interpretation

The National ALS Registry is a multifaceted research platform, one component of which is funded research. This Registry‐funded research fills an essential gap in the overall ALS scientific community as it is difficult to prevent and treat a disease without a deeper understanding of its causes.
Analysis of Abnormal Texture and Strengthening Mechanisms of Extruded Mg–Gd–Y–Nd–Zr Alloy
Authors: Gao Zexi , Liu Chuming , Jiang Shunong , Gao Yonghao , Wan Yingchun , Chen Zhiyong
Published: October 2022

The formation mechanism of an abnormal texture with <0001> orientation parallel to the extrusion direction (<0001>//ED) and strengthening mechanisms in the extruded Mg–Gd–Y–Nd–Zr alloy are investigated. When extruded at a ratio of 25, the abnormal texture is accompanied by a completely dynamic recrystallized (DRXed) microstructure, and its intensity increases with increasing extrusion temperature. When the extrusion ratio is reduced to 9, the multiple texture components are formed, accompanied by nonuniform microstructures. Rare‐earth (RE) elements segregating at the grain boundary or existing as a secondary phase affect the activation of nonbasal slips and preferential growth of DRXed grains. The formation mechanisms of abnormal texture are completed DRX, the operation of pyramidal  slip, and growth advantage. The strengthening mechanisms in the extruded Mg–Gd–Y–Nd–Zr alloy mainly include solid solution strengthening, grain boundary strengthening, and precipitate strengthening, among which solid solution strengthening plays a key role. The trade‐off between the three strengthening mechanisms results in the stability of the mechanical properties of the extruded Mg–Gd–Y–Nd–Zr alloy under various extrusion conditions.
Less is More: Preorganization Leads to Better Tumor Retention and Therapeutic Efficacy
Authors: Xie Limin , Ding Yinghao , Wang Yuhan , Li Xinxin , Yang Zhimou , Hu Zhi‐Wen
Published: October 2022

Protein preorganization is ubiquitous in nature and enables subtle structural rearrangements and precise function executions, making it an attractive approach for generating functional peptide materials. Here, a phosphorylation‐dependent pre‐organization approach to optimize the therapeutic outcomes of a self‐assembling peptide targeting programmed cell death ligand 1 (PD‐L1) is reported. Upon incorporating the imaging probe cyanine 5.5 (Cy5.5) and therapeutic drug 10‐hydroxycamptothecin (HCPT), three phosphorylated precursors (1P, 2P, and 3P) containing identical peptide sequences with different tyrosine phosphorylation sites are constructed. The presence of a phosphate group can stabilize the self‐assembling peptide in a well‐defined, preorganized state. Moreover, variations in the phosphorylation sites lead to different preorganized secondary structures, dephosphorylation rates, and PD‐L1 binding affinities. Responding to alkaline phosphatase dephosphorylation, subtle structural transformation to more ordered states, an increase in binding affinity against PD‐L1, and rapid cellular internalization are observed. Compared with the unphosphorylated control (0P), the preorganization of 1P, 2P, and 3P can optimize tumor retention and resultant therapeutic performance, of which 3P maximizes the final therapeutic outcomes, leading to a 70.3% tumor inhibition rate. This study highlights the great potential to control the subtle structural transformation and therapeutic effects of self‐assembling peptides by preparing their preorganized entities.
Gradient Perovskite Ionic–Electronic Heterointerphases for Deep Cycling Mg Metal Anodes
Authors: Wang Aoxuan , Xue Linlin , Guo Longyuan , Peng Chengxin , Luo Jiayan
Published: October 2022

Direct use of metals with low redox potential and high capacity as anodes can enable high energy density batteries. Mg metal has been considered as an ideal anode for its high critical current density and earth‐abundance, but its development has been impeded by the lacking of Mg‐compatible yet cost‐effective electrolyte. Artificial layers that prevent direct Mg‐electrolyte contact while permit Mg2+ to transport through, mitigate the anode–electrolyte incompatibility and allow industrial Li battery electrolyte analog to implement. However, charge transport through these artificial layers remains elusive, let alone to quantitatively design the layer thickness, components, and their distribution. Here it is shown that by using a gradient mixed ion‐electron conducting layer, which is prepared by a transferable perovskite film, the ion/electron transport path can be individually and continually tuned. It is found that a high Coulombic efficiency of 99.2% can be obtained for Mg anode in 0.5 M Mg(TFSI)2/DME electrolyte. It is also shown that long cycling full cells with a low N/P ratio (N/P ≈ 3.42 for Mg|Mo6S8, N/P ≈ 2.06 for Mg|Cu2‐xS) can be achieved. It is suggested that rational interfacial engineering will open new way to design practical Mg metal batteries.
Deoxyribonucleic Acid‐Based Electron Selective Contact for Crystalline Silicon Solar Cells
Authors: Tom Thomas , Ros Eloi , Rovira David , López‐Vidrier Julian , Asensi José Miguel , Ortega Pablo , Puigdollers Joaquim , Voz Cristobal , Bertomeu Joan
Published: October 2022

Development of carrier selective contacts for crystalline silicon solar cells has been recently of great interest toward the further expansion of silicon photovoltaics. The use of new electron and hole selective layers has opened an array of possibilities due to the low‐cost processing and non‐doping contacts. Here, a non‐doped heterojunction silicon solar cell without the use of any intrinsic amorphous silicon is fabricated using Deoxyribonucleic acid (DNA) as the electron transport layer (ETL) and transition metal oxide V2O5 as the hole transport layer (HTL). The deposition and characterization of the DNA films on crystalline silicon have been studied, the films have shown a n‐type behavior with a work function of 3.42 eV and a contact resistance of 28 mΩ cm2. This non‐doped architecture has demonstrated a power conversion efficiency of 15.6%, which supposes an increase of more than 9% with respect to the cell not containing the biomolecule, thus paving the way for a future role of nucleic acids as ETLs.
Clustered Regularly Interspaced short palindromic repeats‐Based Microfluidic System in Infectious Diseases Diagnosis: Current Status, Challenges, and Perspectives
Authors: Xie Yi , Li Huimin , Chen Fumin , Udayakumar Srisruthi , Arora Khyati , Chen Hui , Lan Yang , Hu Qinqin , Zhou Xiaonong , Guo Xiaokui , Xiu Leshan , Yin Kun
Published: October 2022

Mitigating the spread of global infectious diseases requires rapid and accurate diagnostic tools. Conventional diagnostic techniques for infectious diseases typically require sophisticated equipment and are time consuming. Emerging clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated proteins (Cas) detection systems have shown remarkable potential as next‐generation diagnostic tools to achieve rapid, sensitive, specific, and field‐deployable diagnoses of infectious diseases, based on state‐of‐the‐art microfluidic platforms. Therefore, a review of recent advances in CRISPR‐based microfluidic systems for infectious diseases diagnosis is urgently required. This review highlights the mechanisms of CRISPR/Cas biosensing and cutting‐edge microfluidic devices including paper, digital, and integrated wearable platforms. Strategies to simplify sample pretreatment, improve diagnostic performance, and achieve integrated detection are discussed. Current challenges and future perspectives contributing to the development of more effective CRISPR‐based microfluidic diagnostic systems are also proposed.
Transition‐Metal‐Free Methods for the Remote C−H Bond Functionalization of Cyclic Amines
Authors: Chen Weijie , Cao Xi , Yang Xiaoyu
Published: October 2022

C−H bond functionalization is one of the most efficient strategies for the rapid synthesis of cyclic amines containing substituents in the ring, which are core structures of many bioactive molecules. However, it is much more challenging to perform this strategy on remote C−H bonds than on α‐C−H bonds of cyclic amines. This review provides a comprehensive overview on the transition metal‐free methods for the remote C−H bond functionalization of cyclic amines, complementary to methods relying on transition metal catalysis. Selected substrate scope and discussion of reaction mechanism are given when necessary.
Correspondence on “Synergy and Antagonism between Allosteric and Active‐Site Inhibitors of Abl Tyrosine Kinase”**
Authors: Jahnke Wolfgang , Paladini Johannes , Habazettl Judith M. , Wiget Andrea , Loo Alice , Cowan Jacob Sandra W. , Grzesiek Stephan , Manley Paul W.
Published: October 2022

Soellner published on the interplay between allosteric and adenosine triphosphate (ATP)‐competitive inhibitors of ABL kinase, showing that the latter preferably binds to different conformational states of ABL compared to allosteric agents that specifically target the ABL myristate pocket (STAMP) and deducing that asciminib cannot bind to ABL simultaneously with ATP‐competitive drugs. These results are to some extent in line with ours, although our analyses of dose–response matrices from combinations of asciminib with imatinib, nilotinib or dasatinib, show neither synergy nor antagonism, but suggest additive antiproliferative effects on BCR‐ABL‐dependent KCL22 cells. Furthermore, our X‐ray crystallographic, solution nuclear magnetic resonance (NMR), and isothermal titration calorimetry studies show that asciminib can bind ABL concomitantly with type‐1 or ‐2 ATP‐competitive inhibitors to form ternary complexes. Concomitant binding of asciminib with imatinib, nilotinib, or dasatinib might translate to benefit some chronic myeloid leukaemia patients.
Design of a Protein with Improved Thermal Stability by an Evolution‐Based Generative Model
Authors: Tian Pengfei , Lemaire Adrien , Sénéchal Fabien , Habrylo Olivier , Antonietti Viviane , Sonnet Pascal , Lefebvre Valérie , Isa Marin Frederikke , Best Robert B. , Pelloux Jérôme , Mercadante Davide
Published: October 2022

Efficient design of functional proteins with higher thermal stability remains challenging especially for highly diverse sequence variants. Considering the evolutionary pressure on protein folds, sequence design optimizing evolutionary fitness could help designing folds with higher stability. Using a generative evolution fitness model trained to capture variation patterns in natural sequences, we designed artificial sequences of a proteinaceous inhibitor of pectin methylesterase enzymes. These inhibitors have considerable industrial interest to avoid phase separation in fruit juice manufacturing or reduce methanol in distillates, averting chromatographic passages triggering unwanted aroma loss. Six out of seven designs with up to 30 % divergence to other inhibitor sequences are functional and two have improved thermal stability. This method can improve protein stability expanding functional protein sequence space, with traits valuable for industrial applications and scientific research.
Photoinduced Promiscuity of Cyclohexanone Monooxygenase for the Enantioselective Synthesis of α‐Fluoroketones
Authors: Peng Yongzhen , Wang Zhiguo , Chen Yang , Xu Weihua , Hu Yujing , Chen Zhichun , Xu Jian , Wu Qi
Published: October 2022

The development of mild, efficient, and enantioselective methods for preparing chiral fluorinated compounds has been a long‐standing challenge. Herein, we report a promiscuous cyclohexanone monooxygenase (CHMO) for the photoinduced synthesis of chiral α‐fluoroketones via enantioselective reductive dehalogenation of α,α‐halofluoroketones. Wild‐type CHMO from Acinetobacter sp. possesses this promiscuous ability innately; however, the yield and stereoselectivity are low. A structure‐guided rational design of CHMO improved the yield and stereoselectivity remarkably. Mechanistic studies and molecular simulations demonstrated that this photoinduced CHMO catalyzes the reductive dehalogenation via a novel electron transfer (ET)/proton transfer (PT) mechanism, distinct from that of previously reported reductases with similar promiscuity. This methodology was expanded to various substrates, and desirable chiral α‐fluoroketones were obtained in high yields (up to 99 %) and e.r. values (up to 99:1).
Bioactive Ion‐Based Switchable Supercapacitors
Authors: Li Panlong , Bräuniger Yannik , Kunigkeit Jonas , Zhou Hanfeng , Ortega Vega Maria Rita , Zhang En , Grothe Julia , Brunner Eike , Kaskel Stefan
Published: October 2022

Switchable supercapacitors (SCs) enable a reversible electrically‐driven uptake/release of bioactive ions by polarizing porous carbon electrodes. Herein we demonstrate the first example of a bioactive ion‐based switchable supercapacitor. Based on choline chloride and porous carbons we unravel the mechanism of physisorption vs. electrosorption by nuclear magnetic resonance, Raman, and impedance spectroscopy. Weak physisorption facilitates electrically‐driven electrolyte depletion enabling the controllable uptake/release of electrolyte ions. A new 4‐terminal device is proposed, with a main capacitor and a detective capacitor for monitoring bioactive ion adsorption in situ. Ion‐concentration control in printed choline‐based switchable SCs realizes switching down to 8.3 % residual capacitance. The exploration of adsorption mechanisms in printable microdevices will open an avenue of manipulating bioactive ions for the application of drug delivery, neuromodulation, or neuromorphic devices.
Native Top‐Down Mass Spectrometry Reveals a Role for Interfacial Glycans on Therapeutic Cytokine and Hormone Assemblies
Authors: Wu Di , Robinson Carol V.
Published: October 2022

Oligomerization and glycosylation modulate therapeutic glycoprotein stability and efficacy. The interplay between these two critical attributes on therapeutic glycoproteins, is however often hard to define. Here, we present a native top‐down mass spectrometry (MS) approach to assess the glycosylation status of therapeutic cytokine and hormone assemblies and relate interfacial glycan occupancy to complex stability. We found that interfacial O‐glycan stabilizes tumor necrosis factor‐α trimer. On the contrary, interferon‐β1a dimerization is independent of glycosylation. Moreover, we discovered a unique distribution of N‐glycans on the follicle‐stimulating hormone α subunit. We found that the interfacial N‐glycan, at Asn52 of the α subunit, interacts extensively with the β subunit to regulate the dimer assembly. Overall, we have exemplified a method to link glycosylation with assembly status, for cytokines and hormones, critical for informing optimal stability and bioavailability.
Orthogonally Integrating Programmable Structural Color and Photo‐Rewritable Fluorescence in Hydrazone Photoswitch‐bonded Cholesteric Liquid Crystalline Network
Authors: Lan Ruochen , Bao Jinying , Li Zhaozhong , Wang Zizheng , Song Chenjie , Shen Chen , Huang Rui , Sun Jian , Wang Qian , Zhang Lanying , Yang Huai
Published: October 2022

Design and fabrication of advanced security label showing superior performance in data encryption has attracted tremendous scientific interests. Especially, multifunctional optical labels capable of storing distinct information in different modes are highly demanded. Here, a fluorescent cholesteric liquid crystalline network (CLCN) film with programmable visible patterns and photo‐rewritable fluorescent patterns was designed and prepared. The visible patterns were fixed by helical network and the colors of visible patterns were tunable by changing relative humidity (RH). The fluorescent patterns originated from dynamic isomerization of fluorescent hydrazones, exhibiting highly thermal stability and switching‐ability controlled by light. The orthogonal construction of visible and fluorescent pattern enabled the novel CLCN to encrypt distinct information in reflective mode and in emissive mode, indicating its potential in anti‐counterfeiting and information encryptions.
Coordination Switch Drives Selective C−S Bond Formation by the Non‐Heme Sulfoxide Synthases**
Authors: Wu Peng , Gu Yang , Liao Langxing , Wu Yanfei , Jin Jiaoyu , Wang Zhanfeng , Zhou Jiahai , Shaik Sason , Wang Binju
Published: October 2022

The non‐heme iron ergothioneine synthase (EgtB) is a sulfoxide synthase that catalyzes oxidative C−S bond formation in the synthesis of ergothioneine, which plays roles against oxidative stress in cells. Despite extensive experimental and computational studies of the catalytic mechanisms of EgtB, the root causes for the selective C−S bond formation remain elusive. Using quantum mechanics/molecular mechanics (QM/MM) calculations, we show herein that a coordination switch of the sulfoxide intermediate is involved in the catalysis of the non‐heme iron EgtB. This coordination switch from the S to the O atom is driven by the S/π electrostatic interactions, which efficiently promotes the observed stereoselective C−S bond formation while bypassing cysteine dioxygenation. The present mechanism is in agreement with all available experimental data, including regioselectivity, stereoselectivity and KIE results. This match underscores the critical role of coordination switching in the catalysis of non‐heme enzymes.