bluuebunny/crossref_metadata_2025 huggingface dataset:
HUBUNGAN INTENSITAS MENONTON TAYANGAN KEKERASAN DI TELEVISI DENGAN PERILAKU AGRESIF YANG DILAKUKAN ANAK USIA SEKOLAH DI MADRASAH DINIYAH AWALIYAH NURUL HUDA PAJAR BULAN
Authors: Amelia Riski , Fitriyani Ruri
Published: February 2023

This  study  purpose  to  determine  the  relationship  of  the  intensity  of  watching  violence  on television with aggressive behavior in school-aged children in Madrasah Diniyah Awaliyah Nurul Huda  Pajar  Bulan.  The  hyphotesis  proposed  in  this  research  is  there  is  correlation  between intensity  of  watching  violence  on  television  with  aggressive  behavior  in  school-aged  children  in Madrasah  Diniyah  Awaliyah  Nurul  Huda  Pajar  Bulan.  The  higher  the  aggressive  behavior,  and vice versa the lower the intensity of watching violence on television, the lower aggressive behavior. Of subjects used in this study were 70 students/grade III and IV Madrasah Diniyah  Nurul Huda Pajar Bulan aged 10-12 years. Data collection using two kinds of scale, the scale of the intensity of watching violence on the television and aggressive behavior scale. Data anayisis methods used in the  study  is  the  simple  regression  analysis.  All  caunting  data  analysis  was  performed  using  the computer  program  SPSS  version  17.  The  resuld  of  the  analysis  obtained  corellation  coefisien  of R=0,807, P=0,000 means that the hypothesis is accepted
DEVELOPMENT OF MURINE STEM CELLS WITH CONDITIONAL KNOCKOUT OF HUMANIZED SNCA GENE
Authors: Patrakhanov E. A. , Pokrovsky V. M. , Karagodina A. Yu. , Krayushkina A. M. , Zhunusov N. S. , Deykin A. V. , Korokin M. V. , Pokrovsky M. V. , Altukhova O. B.
Published: February 2023

α-synuclein is one of the key molecular links in the pathogenesis of Parkinson’s disease. The accumulated data indicate that pathogenic mutations in theSncagene are associated with the development of neurodegenerative brain damage, indicating the relevance of studying the synuclein neurobiological role.

The aimof the study was to create a genetically modified clone of mouse stem cells with a conditional knockout of humanized α-synuclein, which can be used for the reinjection into mouse blastocysts, as well as for basic and appliedin vitroresearch in the field of pathophysiology and neuropharmacology.

Materials and methods.To create mouse stem cells with a conditional knockout of the humanizedSncagene, a previously obtained clone with the firstSncaexon flanked by LoxP sites, was used. The CRISPR/Cas9-mediated homologous recombination system with donor DNA oligonucleotides of the human sites of the corresponding gene sites was used to humanize the fourth and fifth exons. Cas9 nuclease, single guide RNA, and donor DNA were transfected into mouse cells.

Results.An approach to obtaining clones of mouse genetically modified stem cells expressing pathological humanized α-synuclein, has been proposed and implemented. The resulting clones were plated on Petri dishes for propagation and a further genetic analysis. Clone 126-2F4 was found out carrying the necessary genetic modifications. The results obtained are fundamentally important not only for understanding the development of the pathological process in α-synucleinopathies, but which is more important, for the development of new therapeutic approaches that will stop the extension of the human α-synuclein aggregation pathology throughout the nervous system, and the validation of these approaches in preclinical trials.

Conclusion.As a result of the study, a strategy for CRISPR/Cas9-assisted homologous recombination in the genome of mouse embryonic stem cells has been developed to create a fully humanizedSncagene encoding α-synuclein, and the clone genome of mouse embryonic stem cells has been edited using a CRISPR technology. The RNA and DNA oligonucleotides necessary for the creation of RNP complexes that carry out a directed homologous recombination in theSncalocus of the mouse genome have been synthesized. The developed cell clone can serve to create a line of genetically modified mice that serve as a test system for pathophysiological and neuropharmacological studies associated with synucleinopathies. Herewith, before the induction of the Cre-dependent recombination, this line is a representative model for studying a biological role of mutantSnca. At the same time, after a Cre-dependent knockout activation, it is possible to imitate the pharmacological inhibition of α-synuclein, which is of particular interest for applied research in neuropharmacology.
HYPOGLYCEMIC EFFECT OF SITAGLIPTIN AND AMINOGUANIDINE COMBINATION IN EXPERIMENTAL DIABETES MELLITUS
Authors: Kurkin D. V. , Bakulin D. A. , Morkovin E. I. , Gorbunova Yu. V. , Strygin A. V. , Andriashvili T. M. , Sokolova A. A. , Bolokhov N. S. , Pustynnikov V. E. , Fomichev E. A.
Published: February 2023

The aim of the work was to determine the antidiabetic effect of a sitagliptin and aminoguanidine combination in rats with experimental diabetes mellitus.

Materials and methods. The study was carried out on male Wistar rats and C57BL/KsJ-db/db mice. According to the models used, it was divided into 4 series, in which alloxan, steroid-induced (dexamethasone) and streptozotocin-nicotinamide-induced diabetes mellitus (DM) were formed, respectively, in rats, and in the 4 series, obese C57BL/KsJ-db/db mice were used. In the 1 and 2 series, the treatment was started prophylactically – 3 h after the alloxan administration and simultaneously with the dexamethasone administration, in the 3rd and 4th series, the treatment was carried out after the pathology had developed – 7 days after the streptozotocin with nicotinamide administration, and in the obese mice – immediately after their distribution according to the groups. The treatment was carried out with sitagliptin (10 mg/kg), aminoguanidine (25 mg/kg), or a combination thereof. The treatment was continued till the end of the experiment, which was completed with an oral glucose tolerance test (OGTT) after 4 h of fasting. The obtained data were subjected to statistical processing.

Results. In the course of the experiments, it was found out that the prophylactic administration of a sitagliptin and aminoguanidine combination, unlike each of the components, prevented the development of alloxan DM. More effectively than the administration of sitagliptin alone, it reduced the severity of steroid-induced DM, which was expressed in a significantly lower level of fasting glycemia (after 4 h of fasting) and postprandial glycemia (during OGTT). Under the conditions of streptozotocin-nicotinamide-induced DM, the studied combination slowed down the progression of the pathology, and in the obese mice, the course therapeutic administration of sitagliptin and its combination reduced the severity of carbohydrate metabolism disorders (fasting glycemia) and increased the rate of glucose utilization.

Conclusion. As an iNOS blocker, aminoguanidine enhances the antidiabetic effect of sitagliptin, preventing the development of alloxan diabetes and reducing the severity of steroid-induced DM when administered prophylactically. When administered therapeutically, it reduces the severity of streptozotocin-nicotinamide-induced DM in rats and type 2 DM in mice with a predisposition to obesity.
DF-5 COMPOUND DELAYS DEVELOPMENT OF DIABETIC NEPHROPATHY IN RATS
Authors: Spasov A. A. , Zhukovskaya O. N. , Rashchenko A. I. , Brigadirova A. A. , Litvinov R. A. , Gurova N. A. , Smirnov A. V. , Pan’shin N. G. , Abbas H. S.A. , Morkovnik A. S.
Published: February 2023

Advanced glycation end-products play an important role in the development of diabetic complications, so slowing down of glycated proteins’ cross-links formation have been suggested as a potential therapeutic option for the treatment of vascular diabetic complications and preventing their progression.

The aim of the work was to assess the influence of novel anticrosslinking agent DF-5 on the renal advanced glycation end-products and collagen contents, body weight, blood glucose and glycated hemoglobin levels and the development of early renal disease in streptozotocin-induced diabetic rats.

Materials and methods. 40 male Sprague-Dawley rats were used in the study. Two months after inducing diabetes, the study substance was administered intragastrically once a day for 28 days (12.5 mg/kg). Measurements included the assessment of blood glucose and HbA1c levels, the evaluation of the renal function, and the results of histology and immunohistochemical staining of kidneys.

Results. A repeated intragastric administration of DF-5 for 30 days significantly reduced the level of HbA1c in the blood, but did not affect the level of fasting blood glucose. DF-5 compound significantly reduced proteinuria and prevented kidney damage in experimental animals by limiting damage of the glomeruli and tubules. It was found that DF-5 inhibits the progression of an early renal dysfunction in rats with streptozotocin-induced diabetic nephropathy. This was associated with a decreased accumulation of advanced glycation end-products in the kidney, accompanied by the improvement of both renal morphology and function.

Conclusion. The results obtained provide investigators with additional therapeutic options for the treatment of diabetic nephropathy and possibly other complications of diabetes.
BIOEQUIVALENCE STUDY OF GENERIC MOLNUPIRAVIR IN HEALTHY VOLUNTEERS
Authors: Vasilyuk V. B. , Boroduleva A. Yu. , Sobolev P. D. , Nikiforova A. G. , Mozgovaya V. G. , Filon O. V. , Zinkovskaya A. V. , Ignatiev V. G. , Samsonov M. Yu. , Kozlova I. S. , Khanonina E. K.
Published: February 2023

Molnupiravir is one of the drugs for the etiotropic therapy of a new coronavirus infection COVID-19. It has confirmed its clinical efficacy in the treatment of patients with mild and moderate COVID-19, including those who are at high risk of progressing to severe disease.

The aim of the study was to evaluate bioequivalence of the generic drug molnupiravir ALARIO-TL and the original drug Lagevrio with a single oral administration in healthy volunteers.

Materials and methods. This bioequivalence study was an open, randomized, two-period crossover study. In each of the two periods, volunteers received a single dose of the test drug, or reference drug molnupiravir, in the form of capsules at the dose of 200 mg. The washout period between the doses was 3 days. To determine pharmacokinetic (PK) parameters and bioequivalence, the concentration the concentration of N-hydrozycytidine (NHC), the main molnupiravir metabolit in the blood plasma of volunteers was evaluated. The blood plasma sampling was carried out in the range from 0 to 16 hours in each of the study periods. Bioequivalence was assessed by comparing 90% confidence intervals (CIs) for the ratio of geometric means of AUC(0–16) and Cmax of the test drug and reference drugs with the established equivalence limits of 80.00 – 125.00%.

Results. A total of 28 healthy male volunteers were included in the study. According to the results of the statistical analysis, after the administration of the test and reference drugs, the 90% CIs for the ratio of the geometric means of AUC (0–16) and Cmax were 96.31% – 113.64% and 91.37% – 114.8%, respectively. These intervals fit within the established limits of 80.00–125.00%, which confirms the bioequivalence of the drugs. When comparing the frequency of the individual adverse events registration, no significant differences were found out after the administration of the test and reference drugs.

Conclusion. Based on the results of this study, it can be concluded that the test and reference drugs of molnupiravir are bioequivalent. In addition, the data obtained indicate that the drugs have similar safety profiles.
Listy Tomasza Zana z więzienia. Czy w izolacji można pisać rozdziałki?
Authors: Pisula Anna
Published: February 2023

The article attempts to investigate in what way Tomasz Zan’s works changed as a result of author’s experience of isolation while being imprisoned. Rozdziałki, a genre original to the author, develop parallelly with Zan’s biography. They reflected the feeling of loneliness and other circumstances of his time in prison by measures such as the poetics of dreams and imagination, the use of a specific literary codes and elements of grotesque. The analysis of Zan’s works written in prison leads to the conclusion that the author’s attitude towards literature evolved during his life, and especially as a result of his imprisonment.
„Zoöpolis” — miasto ludzi i zwierząt
Authors: Barcz Anna
Published: February 2023

Tekst jest komentarzem do polskiego przekładu Zoöpolis Jennifer Wolch, w którym amerykańska badaczka postuluje międzygatunkową teorię miasta. Barcz przedstawia najważniejsze problemy podjęte przez Wolch oraz pokazuje, co koncepcja zoöpolis ma do zaproponowania antropocentrycznym studiom miejskim. Ekologizuje ona bowiem zarówno studia nad miastem, jak i samą koncepcję nowoczesnego „miasta-kultury”.
Life course decisions in Central and Eastern Europe: A gendered connection between family formation and moving intentions?
Authors: Deimantas Vytenis Juozas
Published: February 2023

Objective: This paper investigates the association between family formation intentions of marriage and childbearing in connection to moving intentions in early life course in Central and Eastern Europe.
Background: While connections between intentions in Western Europe has received some scholarly attention, the link between marriage, having children and moving intentions has been largely overlooked in Central and Eastern Europe. We look at the connection between these intentions in the region.
Method: We hypothesise that intentions to marry, have children and move may be positively related, negatively related or not related at all; and that gender serves as a channel through which the connection between family formation intentions and intention to move is expressed. In order to verify the hypotheses, we use Generations and Gender Survey data round 1 wave 1 focusing on the analytical sample based on individuals between 17 and 49 year olds from 5 Central and Eastern European countries. We run seemingly unrelated bivariate ordered probit regressions to estimate the relationship between the intentions.
Results: We find a positive association between family formation intentions and intention to move. However, there is no evidence suggesting this association is channelled through gender.
Conclusion: There exists an indication that intentions of marriage, childbearing and moving are joint.
Análise preliminar dos riscos ambientais da Bacia do Rio Uraim, em um Município da Amazônia Oriental
Authors:   Universidade do Estado do Pará, Sardinha Aline Souza , Ventura Katia Sakihama ,   Universidade Federal de São Carlos
Published: February 2023

This work proposes a preliminary analysis of the environmental risks caused in the Uraim River basin, in which the river that names it is used as a source of water supply in the municipality of Paragominas, State of Para, Brazil. The method used was deductive, as it is based on two true premises: (1) The river basins are altered by human actions, (2) the quality of the source of water supply becomes a challenge for the operators of water treatment plants. (WTP). The predominant activities in the municipality are livestock, agriculture, mining, logging and trade in services. The results showed that the Uraim River basin has high deforestation of native vegetation. Twelve areas of high and very high risk of a mass movement and flooding were identified, which are associated with the disorderly expansion of the urban area, combined with the geomorphology and geology of the region. It is recommended that the Uraim River basin committee be implemented, so that its watershed management can take place, in the incessant search for improving the quality of source of water supply, so that it is feasible to capture, treat and distribute safety drinking water to the population.
Avaliação qualitativa do efeito de histereses entre vazão e concentração de sedimentos em suspensão no rio Jundiaí, SP
Authors:   Universidade Estadual de Campinas, Bermúdez Luis Fernando Murillo , Martin André Luís Sotero Salustiano ,   Universidade Estadual de Campinas
Published: February 2023

Hydrosedimentological dynamics in watersheds show a non-linearity and the factors that intervene are still the subject of debate in the scientific context. The present work, through qualitative analysis of the hysteresis effect between measured flow data and suspended sediment concentration data correlated with turbidity values, sought to preliminarily evaluate some of the variables that interfere in the sediment transport process. As a result, a description of 17 rainfall events was obtained for high flows where the predominance was of type eight, related to events with multiple discharge peaks that connect different sources of sediments upstream of the measurement point, generating patterns with greater complexity.
Ecotoxicidade de esgoto tratado como um parâmetro operacional em ETES
Authors:   Universidade Estadual de Campinas, Almeida Gabriela Cristina Fonseca , Umbuzeiro Gisela de Aragão ,   Universidade Estadual de Campinas
Published: February 2023

Aquatic ecosystems are used as destination of urban effluents. According to Brazilian regulation, final effluents must not have the potential to cause impact on the receiving body and, to assess this impact, toxicity tests are required. The objective of this work was to evaluate the acute toxicity with Daphnia similis and chronic with Ceriodaphnia dubia of final effluents from 4 sewage plants (ETEs, named A, B, C and D) from Campinas, SP, Brazil, with different treatments’ levels. Six monthly campaigns were carried out in 2022 and samples were collected before and after chlorination. The effluents from ETE B showed acute toxicity in all campaigns, and effluents from ETE A and C showed acute toxicity in at least one campaign, but with low toxicity (EC50, 48h >50%). Chronic toxicity was detected in all effluents, except in ETE D (reuse water production station) indicating the great efficiency of the treatment of membrane bioreactors (MBR). Acute tests with fish embryos (FET) will be performed to compare the results of tests with cladocerans. The evaluation of the impact potential of the effluents will also be carried out based on the average of effluent discharges and in reference to the respective receiving bodies.
El k’in tajimoltik, el mono, el kaxlan y el tigre
Authors: Zermeño Fabiola del Rosario , Montoya David
Published: February 2023

En San Juan Chamula, municipio ubicado en la región de Los Altos del estado mexicano de Chiapas, el carnaval es concebido como una fiesta grande, pues además de realizarse de manera simultánea en diversos escenarios, congrega a un gran número de personas: tanto espectadores como cargos requeridos. Del tiempo de Carnaval, conocido en lengua tsotsil como Febrero Loko, sobresale el humor, la diversión; no obstante, una propiedad menos visible o, hasta cierto punto, oculto, cuando menos a los ojos de los visitantes, remite a tiempos primigenios, al ordenamiento del cosmos y a la creación de la humanidad. De ahí que también se conozca localmente como k’in tajimoltik, en alusión a la celebración de “nuestros mayores”.El objetivo central de esta celebración es mantener con vigencia la legitimidad de los bats’i viniketik, la última humanidad: La que sabe relacionarse socialmente con sus ancestros, sus creadores, sus kajvaltik (dueños).Según da cuenta la tradición oral, cuando Dios-Sol vivía en la Tierra fue perseguido por seres malignos - demonios, judíos, entre otros - y fue el jaguar, quien figura como su “animal compañero”, quien lo defendió cuando estos seres intentaban matarlo. De esta forma, cada vez que una persona se une a la danza del chilon , con la piel de jaguar sobre su espalda, establece un vínculo social con el jaguar de Dios y, al mismo tiempo, con Dios, entre humanos y con otros seres (no humanos).Los monos libres o kolemal maxetik son los cargos más numerosos, están asociados a la música y el baile y, por su conducta, guardan relación con las humanidades pasadas. Éstos condensan una multiplicidad de alteridades con las que el chamula se ha relacionado de manera histórica y mitológica. Sin un rumbo preciso, sin la guía de sus kajvaltik, los kolemal recorren la cabecera municipal y hacen partícipes de la danza del chilon a los turistas. Sin saberlo, el visitante, ladino, extranjero, kaxlan, grinko o alemán, se vuelve uno de los principales actores de esta re-creación cósmica: figuran como las humanidades pasadas.
“O som dos sinos”
Authors: Mansur Marcia , Thomé Marina
Published: February 2023

Em 2009, o Toque dos Sinos e o Ofício de Sineiro foram registrados pelo Instituto do Patrimônio Histórico e Artístico Nacional (IPHAN) como Patrimônios Culturais Imateriais Brasileiros. O registro é fruto de um inventário que mapeia, em 9 cidades de Minas Gerais, mais de 40 tipos de toques de sinos, que formam uma linguagem sonora através da qual moradores das cidades de Minas Gerais se comunicavam, sobretudo, entre os séculos XVII e XIX. Havia toques de sinos distintos para anunciar o falecimento de homem, de mulher ou de criança; outros toques identificavam missas, procissões, festas, incêndios, partos. Os toques dos sinos são uma forma de comunicação não-verbal, que trazem em si significados diversos, constituídos das memórias e histórias dos habitantes da região. Os sineiros, responsáveis por tocar os sinos, transmitem o conhecimento dos toques, badaladas, ritmo e harmonia para as novas gerações no contexto da tradição oral/aural. Ensina-se e aprende-se através de observação, escuta e prática, no alto das torres, durante as festividades, nos dias de missa – mas apenas nas horas propícias de se tocar o sino.
La formación de estrategias para la rápida internacionalización de las pequeñas empresas / The formation of strategies for the rapid internationalization of small firms
Authors: Rialp-Criado Alex , Galván-Sánchez Inmaculada , Suárez-Ortega Sonia Mª
Published: February 2023

Se propone una nueva taxonomía, tras la revisión de diferentes enfoques de formación de estrategias empresariales, para el fenómeno de las pequeñas empresas de rápida internacionalización o born globals, con el objetivo de ampliar su conocimiento. El proceso de formación de estrategias para la internacionalización temprana exitosa tenderá a adoptar un enfoque configuracional y holístico, analizando las distintas fases por las que transita una empresa born global. Así, primero la formación de la estrategia tenderá a ser más emprendedora (estrategia emergente), para, con el paso del tiempo, ir convirtiéndose cada vez más en un proceso planificado y sistemático (estrategia deliberada).
The effectiveness of the magnetic ring (LINX®) Device in managing reflux after sleeve gastrectomy; long term results: a seven-years’ experience
Authors: Hawasli Abdelkader , Hallowell Shoshana
Published: February 2023

Aim: The magnetic ring (LINX®) system was approved by the FDA in 2012 as a device to augment the lower esophageal sphincter pressure to manage reflux in the general population. It was introduced into the bariatric population in 2014 as an alternative to Roux-en-Y gastric bypass (RYGB) in managing reflux after sleeve gastrectomy (SG). Materials: Between January 2015 and December 2021, Seventeen patients had the Magnetic Ring (MR) device placement to manage their reflux after SG. Methods: The mean age was 54 ± 12 years. Their mean body mass index (BMI) was 31 ± 6 kg/m2. The mean time between the SG and MR device placement was 41 ± 19 months. The mean DeMeester score was 48 ± 26 (normal < 14.72). Results: All seventeen patients underwent a successful laparoscopic placement of the MR device. Two patients had early post-operative dysphagia requiring removal of the device and one patient was lost to follow-up. The mean follow up of the remaining fourteen patients was 65 ± 31 months. Recurrent reflux occurred in 11 (79%). In three of these eleven (27%) patients the recurrent reflux was due to a broken device. None of these patients were interested in conversion to RYGB. Conclusion: The MR device is a valuable tool in treating reflux after SG in spite of its potential risk of recurrence. Our results can be interpreted as being dissatisfying if complete resolution is the goal. Larger studies, with more than 3 year follow up, are needed before a final decision is made on its value in the bariatric population.
SHARIA’S ECONOMIC LAW PERSPECTIVE ABOUT CASH WAQF IN THE ERA OF THE INDUSTRIAL REVOLUTION FOUR POINTS ZERO
Authors: Ahyani Hisam , Muharir  , Mahfud Muntaha
Published: February 2023

This study aims to determine cash waqf in the view of sharia economic law in the era of the industrial revolution 4.0. The understanding of the Indonesian people regarding cash waqf is still minimal even though this waqf has excellent potential for the welfare of the Indonesian people. Regarding research from the perspective of Islamic economic law on cash waqf in the era of the industrial revolution 4.0, no one has researched it. The method used is literature research, qualitative, with statutory, historical, comparative, and conceptual approaches, and this research is normative. The view of Shariah economics in Indonesia regarding cash waqf is carried out by Law No.41 / 2004 concerning waqf in which moving objects are in the form of “movable object waqf” which is manifested in the form of money. Waqf money in Indonesia in the era of the Industrial Revolution 4.0 can prosper the economy of the people and the country. Waqf is positioned as social worship, wherewith waqf in Law no.41 / 2004 concerning waqf article 1 it is explained that waqf is the act of a wakif to separate or give up part of his property to be used forever for worship purposes and for welfare purposes according to Islamic sharia.
Priority Based Multi Sen Car Technique in WSN
Authors:   Assistant Professor, Department of MCA, Ethiraj CollegeforWomen,Chennai,TamilNadu., Mary D. Sophia Navis , Ms Vidhya.P.L ,   Research Scholar, Department of MCA, Ethiraj College for Women, Chennai,TamilNadu
Published: February 2023

In Wireless sensor network (WSN), Clustering is an efficient mechanism used to overcome energy capability problem, routing and load balancing. This paper addresses energy utilization and load distribution between the clusters. The load balanced clustering algorithms (LBC) used to decrease the energy utilization and distribute load into clusters. The SenCar uses multi-user multi-input and multi-output (MU-MIMO) technique which is introduced the multi SenCar to collects the information from each cluster heads and upload the data in the base station. This method achieves more than 50 percent energy saving per node, 80 percent energy saving on cluster heads and also achieves less data collection time compared to the existing system.
Four‑stage Evolution of Diabetes or Whole‑body Insulin Resistance (WBIR) Driven by Sequential Progression of Tissue‑specific Glycation‑induced Insulin Resistance (GIIR)
Authors: LEE Song Jae , Shin Sang Won
Published: February 2023

The investigation by the integrated approach newly introduced for this study indicates that insulin resistance (IR) would develop first preferentially in the muscle tissue with a relatively low cell turnover and then progress in sequence to the subcutaneous adipose tissue, to the visceral adipose tissue, and to the liver with higher cell turnovers. Moreover, metabolic disruptions due to IR vary widely from tissue to tissue, contrary to the conventional notion that IR merely impairs glucose uptake in the whole body. This warrants that IR be divided better into four distinct tissue specific IRs: muscle insulin resistance (MIR), subcutaneous adipose insulin resistance (s-AIR), visceral adipose insulin resistance (v-AIR), and hepatic insulin resistance (HIR). Tissue-specific IRs developing in the order of MIR, s-AIR, v-AIR, and HIR – producing tissue specific metabolic disruptions – would amount to nothing but the whole body insulin resistance (WBIR) evolving in four distinctively insulin resistant stages. The four stage metabolic evolution from rapid weight gain to visceral obesity to rapid weight loss to full blown diabetes not only complies well with the natural development history of diabetes but also resolves most of the controversies regarding obesity or diabetes, including visceral obesity, obesity paradox, and dawn phenomenon that have long remained metabolic puzzles. In addition, the four-stage WBIR evolution model refutes the entrenched notion of the lipid-induced insulin resistance (LIIR) but supports instead the glycation-induced insulin resistance (GIIR) proposed in this study. A speculation is that the glycation reaction activated ever more with WBIR evolving may serve as the common thread connecting each other a cluster of disorders or diseases that are often collectively referred to as the metabolic syndrome, such as obesity, diabetes, cardio/cerebral vasculopathy, nephropathy, neuropathy, and retinopathy.
Vaginal Microbiota Transplantation: Possible Mechanisms and Future Perspectives
Authors: Tuniyazi Maimaiti , Li Shuang , Fu Yunhe , Hu Xiaoyu , Zhang Naisheng
Published: February 2023

The human body is inhabited by unique microbial communities that protect and regulate the host against pathogens and inflammation. To address issues related to disrupted microbial composition, microbial transfer therapy (MTT) has emerged as a potential treatment option. The most popular form of MTT is fecal microbiota transplantation (FMT), which has been successful in treating various diseases. Another emerging form of MTT is vaginal microbiota transplantation (VMT), transferring of the vaginal microbiota from a healthy female donor to a diseased patient's vaginal cavity, which aims to restore normal vaginal microbial composition. However, VMT is vastly unexplored due to safety concerns and lack of research. This paper explores the mechanisms involved in VMT's therapeutic effect and discusses future perspectives. Further research is needed to advance VMT's clinical applications and techniques.
Improvement of Algan Homoepitaxial Tunnel Junction Deep-UV Light-Emitting Diodes by Controlling the Growth of N-Type Algan and Polycrystalline Mgzno/Al Electrodes
Authors: Nagata Kengo , Matsubara Taichi , Saito Yoshiki , Kataoka Keita , Narita Tetsuo , Horibuchi Kayo , Kushimoto Maki , Tomai Shigekazu , Katsumata Satoshi , Honda Yoshio , Takeuchi Tetsuya , Amano Hiroshi
Published: February 2023

Deep-ultraviolet (UV) light-emitting diodes (LEDs) based on AlGaN crystals have low light-emission efficiency; therefore, there is a need to improve this light-emission efficiency for a wide range of applications such as water and air sterilizations. UV-light-transparent device structures are considered one of the many solutions toward increasing light output power. To this end, the present study focused on developing a transparent AlGaN-based tunnel junction (TJ) as the anode of a deep-UV LED. Deep-UV LEDs composed of n+/p+-type AlGaN TJs were fabricated under the growth condition that reduced the carrier compensation in the n+-type AlGaN layers. The operating voltage was 10.8 V under the direct current (DC) operation of 63 A/cm2. In addition, magnesium zinc oxide (MgZnO)/Al reflective electrodes were fabricated to enhance the output power of the AlGaN homoepitaxial TJ LED. The output power was 57.3 mW under a DC operation of 63 A/cm2, and it was 1.7 times higher than that realized using the conventional Ti/Al electrodes. The combination of the AlGaN-based TJ and MgZnO/Al reflective contact allows further improvement of the light output power. This study confirms that the AlGaN TJ is a promising UV-transmittance structure that can obtain a high light-extraction efficiency.
AI-Predicted mTOR Inhibitor Reduces Cancer Cell Proliferation and Extends the Lifespan of C. elegans
Authors: Vidovic Tinka , Dakhovnik Alexander , MacArthur Michael R , Ewald Collin Y.
Published: February 2023

The mechanistic target of rapamycin (mTOR) kinase is one of the top drug targets for promoting health and lifespan extension. Besides rapamycin, only a few other mTOR inhibitors have been developed and shown their ability to slow aging. We used machine learning to predict novel small molecules targeting mTOR. We selected one small molecule, TKA001, based on in-silico predictions of a high on-target probability, low toxicity, favorable physicochemical properties, and preferable ADMET profile. We confirmed TKA001 binding in silico by molecular docking. TKA001 potently inhibits both TOR complex 1 and 2 downstream signaling in vitro. Furthermore, TKA001 inhibits human cancer cell proliferation in vitro and extended the lifespan of C. elegans, suggesting that TKA001 can slow aging in vivo.
Price Based Load Frequency Control With Bidirectional Charg-ing Mechanism With EV
Authors: Prajapati Yogeshkumar
Published: February 2023

Contract violations, uncontracted load, and the alternating nature of electricity are the key causes of the frequency irregularity and Unscheduled Interchange (UI) / Deviation Settlement pricing in a restructured organized smart grid. These variations cause the frequency to fluctuate. The topic of frequency variation is discussed in this paper under various market circumstances. To correct frequency discrepancies under various market conditions, a fleet of electrical vehicles (EV) is offered as a distributed energy storage (DES). A bidirectional charger with a PI controller is suggested for the EV bidirectional power transfer. It is suggested to use a fuzzy logic (FL) controller to modify the proportional-integral (PI) controller gains. It has been noted that utilizing such a new approach lowers the UI prices.
Mapeamento dos bancos de dados em dispositivos médicos: revisão narrativa e o cenário brasileiro para avaliação com dados de mundo real (RWD
Authors: Toscas Fotini , Teixeira Leidy
Published: February 2023

Objetivo: Pretendeu-se mapear os bancos de dados governamentais em dispositivos médicos, na perspectiva pública com o intuito de contribuir como fonte para gerar dados de mundo real (RWD) e potencial para subsidiar estudos de Avaliação de Tecnologias em Saúde (ATS). Métodos: Realizada revisão narrativa na base de dados do Embase. Os critérios para inclusão de elegibilidade foram: i) dimensão ampla de RDW nos processos de gestão de tecnologias; e ii) aplicação de RDW em processos regulatórios, cobertura e ATS. Também foram consultados os sistemas do Ministério da Saúde e da Anvisa. Resultados: A busca retornou 1.185 resultados; após leitura dos resumos, foram selecionados 29 artigos, sendo 5 incluídos. Na consulta ao catálogo do Datasus, foram localizados 262 sistemas informatizados; após análise da descrição sumária e principais objetivos, foram selecionados 12 sistemas que geram dados sobre dispositivos médicos. A falta de interoperabilidade dos sistemas é recorrente e a ausência de uma nomenclatura padronizada é um desafio a mais. Conclusão: Há crescente discussão do uso de RWD para subsidiar ATS em todo o ciclo de vida tecnológico, desde regulação até monitoramento do uso, como também para subsidiar análises de custo-efetividade e benefícios clínicos. Assim como nos demais países, o Brasil sistematizou inicialmente os dados administrativos para atender às demandas comerciais e financeiras. Os sistemas não geram dados dos resultados clínicos. São disponibilizados dados das tecnologias dispensadas e dos valores repassados e não são coletadas as informações dos benefícios do uso dessas tecnologias. Com a evolução dos métodos de ATS, a utilização de RWD tornou-se relevante.
O uso da cirurgia robótica em artroplastias totais de joelho – Uma nova tecnologia chega ao Brasil
Authors: Ramos Leonardo
Published: February 2023

Com a chegada da cirurgia robótica na cirurgia do joelho no Brasil em 2021, novos questionamentos são feitos para que possamos compreender como essa nova tecnologia pode ser assimilada no contexto da saúde e da realidade do país. As novas tendências no financiamento da saúde relacionadas ao setor privado fazem questionar de que maneira novos procedimentos podem ser incorporados, buscando o equilíbrio entre o avanço tecnológico e a acessibilidade baseada em custos e desfechos relacionados à qualidade de vida dos pacientes.
Guiding Epilepsy Surgery by Intraoperatively Visualizing Proinflammatory Microglia via a Ratiometric Surface-Enhanced Raman Scattering Nanosensor
Authors: Wang Cong , Li Zhi , Zhu Xiao , Ding Yue , Duan Wenjia , Sun Wanbing , Jiang Yiqing , Chen Ming , Hu Jiayi , Cai Zheping , Zhao Jing , Fan Zhen , Zheng Faming , Zhou Xingyu , Xie Fang , Zhang Jianping , Guan Yihui , Xiao Xiao , Chen Liang , Li Cong , Mao Ying
Published: February 2023

Resective surgery is used for long-term seizure control in drug-resistant focal epilepsy when the epileptic focus (EF) can be accurately delineated and removed. However, as the “gold standard” technique for mapping EF intraoperatively, electroencephalography is laborious, time-consuming and highly vulnerable to anaesthesia. Here, we demonstrated hypochlorous acid (HOCl), a bioproduct of activated proinflammatory microglia, can be reliable biomarkers for EF localization. With a newly developed HOCI ratiometric Raman nanosensor, ultraHOCls, we can accurately locate EF in live kainic-acid-induced mice by visualizing proinflammatory microglia ignoring the interference of anaesthesia. Moreover, ultraHOCls provided a 1-hour stable imaging time-window for locating EF, which is more than 100 times longer than single neuroelectric activity recorded by electroencephalography. UltraHOCls-guided surgery showed a 72% reduction in total seizure time in mice in comparison to electroencephalography-guided surgery. This work provides an alternative strategy for locating EF intraoperatively and holds promise in improving surgical outcomes in epilepsy patients.
Application of Machine Learning in Predicting Frailty Syndrome in Patients with Heart Failure
Authors: Szczepanowski Remigiusz , Pasieczna Aleksandra H. , Sobecki Janusz , Katarzyniak Radoslaw , Kołaczek Grzegorz , Lorkiewicz Wojciech , Kędras Maja , Uchmanowicz Izabella , Biegus Jan , Wleklik Marta , Gobbens Robbert J.J. , Hill Loreena , Jaarsma Tiny , Hussain Amir , Barbagallo Mario , Veronese Nicola , Morabito Francesco C. , Dixit Anant , Kahsin Aleksander
Published: February 2023

Background
Prevention and diagnosis of frailty syndrome (FS) in patients with heart failure (HF) requires innovative systems supporting medical personnel to tailor and optimize their treatment and care. Classical methods of diagnosing the FS in patients are not entirely satisfactory. Healthcare personnel in clinical setting use a combination of test and self-reports to diagnose patients and those at risk of frailty, which is time-consuming and costly. Modern medicine uses artificial intelligence (AI) to study the physical and psychosocial domains of frailty in cardiac patients with HF.
Methods
This paper aimed to present the potential of using the AI approach, emphasizing machine learning in predicting frailty in patients with HF. Our team critically scrutinized the literature on machine learning applications for FS syndrome, as well as reviewed frailty measurements applied to modern clinical practice.
Results
Our approach analysis resulted in recommendations of machine learning algorithms for predicting frailty in patients. We also presented the exemplary application of machine learning for frailty syndrome in HF patients based on TFI questionnaire measurements, taking into account psychosocial variables
Conclusions
We recommend AI and machine learning for the holistic and personalized care of patients at risk of the consequences of FS, improve diagnostic tools examining this syndrome, and effective collaboration between psychologists and health care professionals.
Rapid Implementation of Veterans Health Administration Telehealth Creative Arts Therapies: Survey Evaluation of Adoption and Adaptation
Authors: Story Kristin M , Flanagan Mindy , Robb Sheri L. , Bravata Dawn M. , Bair Matthew J. , Otto David , Damush Teresa M.
Published: February 2023

Background: Creative Arts Therapies (CAT) are employed throughout the Veterans Health Administration (VHA) and are predominantly delivered in-person. Due to guidance from the Center for Disease Control and VHA that temporarily suspended or reduced in-person services, CAT therapists adopted telehealth delivery. The aims of this study were to evaluate adoption and adaptation of CAT telehealth delivery and identify related barriers and facilitators.
Methods: We deployed a survey guided by the Consolidated Framework for Implementation Research and administered it via email to all VHA CAT therapists (N=120). Descriptive statistics were used to summarize data and responses were compared based on therapists’ age, years of experience and CAT discipline. Open survey field responses were summarized, qualitatively coded, and analyzed thematically.
Results: Most therapists (76%) reported adopting telehealth with 74% each delivering >50 CAT sessions in the prior year. Therapists adapted interventions or created new ones to be delivered through telehealth. Barriers included: technical challenges, control of the virtual space, and building rapport. Facilitators included added equipment, software, and infrastructure. CAT therapists adapted their session preparation, session content, outcome expectations, and equipment. CAT therapists reported being able to reach more patients and improved access to care with telehealth compared to in person visits. Additional benefits were patient therapeutic effects from attending sessions from home, therapist convenience, and clinician growth.
Conclusions: VHA CAT therapists used their inherent creativity to problem solve difficulties and make adaptations for CAT telehealth adoption. Future studies may explore CAT telehealth sustainment and its effectiveness on clinical processes and outcomes.
Application of the Composite Quality Score (CQS-2B) in systematic reviews of prospective, controlled, clinical therapy trials – a pilot study (Protocol v.2.0)
Authors: Mickenautsch Steffen , Rupf Stefan , Yengopal Veerasamy
Published: February 2023

Objectives: To establish, whether clinical conclusions from systematic reviews that applied the second version of Cochrane’s Risk of Bias tool (RoB 2) remain the same when the Composite Quality Score (CQS-2B) is used, instead.
Methods: PubMed will be searched for one systematic review that complies with the following criteria: At least 20 prospective, clinical, controlled therapy trials included into meta-analyses; computable data for test- and control group reported; trial appraisal using the RoB 2 tool; inclusion of at least 5 trials in at least one single comparison per measured outcome; published in English. All trial reports included in the systematic review will be traced in full copy and the following data extracted per trial: Full reference details; overall RoB 2 appraisal decision; computable datasets. All trial reports will be re-appraised using the CQS-2B. All datasets will be stratified by overall bias risk (RoB 2 tool) and per corroboration (C-) level (CQS-2B). Trial data for each bias risk and C-level will be statistically pooled using Mantel-Haenszel statistics with random-effects model. All pooled ‘low bias risk’ effect estimates (RoB 2) and all pooled effect estimates of the highest C-level with data (CQS-2B) will in turn each be pooled by use of a random effects meta-analysis. DerSimonian and Laird’s method of moments estimator will be used to estimate the between-study variance. Statistical inconsistency will be quantified using the I2 statistic. The pooled effect estimates of both appraisal tools will be statistically compared using the Wald-test and the null-hypothesis tested that both are not significantly different. Clinical conclusions based on the pooled ‘low bias risk’ estimates (RoB 2) and the C4-level (CQS-2B) will be qualitatively compared.
Reporting: The final report will be made available online as preprint in one of the major preprint repositories and submitted to a peer-reviewed journal.
The Dynamic Effects on Bone Mass of Chemotherapy and Surgery in Lung Cancer Patients
Authors: Wang Guoqing , Li Tianyu , Zhang Le , Li Changcheng , LI Jinglei , Cong Jicong , Qin Jian , Li Changqin , Zhu Jianzhong , Li Shen-jiang
Published: February 2023

Background The aim of this study was to evaluate the dynamic effects on bone mass of chemotherapy and surgery in lung cancer patients by computed tomography (CT).
Methods This was a retrospective study, 147 patients with lung cancer from June to December 2021 in our hospital were finally selected. Data consisted of cycle of chemotherapy and surgery. CT scans before chemotherapy and cycle 1-6 after chemotherapy were performed.The CT values of the T11-L1 vertebral body were recorded and compared.
Results The mean CT values of T11-L1 vertebral body in cycle 1, 5and 6 were lower than that in pre-chemotherapy (P=0.007＜0.05，P=0.038＜0.05，P=0.048＜0.05). There was no significant difference among the rest groups (all P＞0.05）. The CT value of T11 was higher than those of L1 in pre-chemotherapy and cycle 1, 2 after chemotherapy (P＜0.001，P=0.042< 0.05，P=0.015< 0.05). There was no statistically significant difference in CT values among the T11,T12 and L1 in cycle 3, 4, 5 and 6 (all P＞0.05). There was no statistical significant difference in the mean CT values of the T11-L1 vertebral body between operation group and non-operation group in pre-chemotherapy and same cycle after chemotherapy (all P＞0.05).
Conclusions Osteodeficiency exacerbated by ongoing chemotherapy and unaffected by operation in lung cancer patients indicates the need for the development of antiosteoporosis treatment and osteoporosis prophylaxis for lung cancer patients.
Outcome and Decision-making Process in Penile Curvature Surgery: a Single-centre Preliminar Experience
Authors: Loria Giada , Stranieri Giuseppe , Talarico Valentina , Fava Antonietta , Raiola Giuseppe , Galati Maria Concetta , Salerno Domenico
Published: February 2023

Penile curvature could represent a great challenge to the paediatric urologist. Surgeons have to choose among several surgical techniques. Degloving and chordee section techniques are able to correct the majority of congenital bent penis. More invasive surgeries should be considered for residual curvature or severe cases. We report 35 cases of paediatric patients suffering from anomalies of penile curvature treated with different surgical approaches. No major complications are disclosed. In the majority of patients, degloving and chordee section resulted to be sufficient to correct the curvature. Further studies on a bigger patients’ population are required to assess the most correct approach to each degree of curvature and associated anomalies. Besides every peculiar anatomic condition, to deal with difficult situation where the line of must-treat is not so marked, in our opinion it is crucial to be able to count on multi-disciplinary teamwork which can accomplish a 360-degrees evaluation of the patients’ health and mental status.
The DUBA-SLC7A11-c-Myc axis is critical for stemness and ferroptosis
Authors: Tao Yongguang , Wang Zuli , Ouyang Lianlian , Liu Na , Li Tiansheng , Yan Bokang , Mao Chao , Xiao Desheng , Gan Boyi , Liu Shuang
Published: February 2023

Ferroptosis is characterized by the accumulation of lipid peroxidation as a unique iron-dependent cell death. However, the interplay between stemness and ferroptosis remains unknown. Here, we demonstrate that undifferentiated cells are more sensitive to ferroptosis than differentiated cells, and cystine transporter SLC7A11 protein is highly up-regulated by deubiquitinase DUBA in differentiated cells. Additionally, DUBA promotes stemness by deubiquitinating SLC7A11. Moreover, SLC7A11 drastically increases the expression of c-Myc through cysteine, the combination of sorafenib and c-Myc inhibitor EN4 has a synergetic effect on cancer therapy. Together, our results reveal that enhanced stemness increases the susceptibility to ferroptosis, and the DUBA-SLC7A11-c-Myc axis is pivotal for differentiated cancer stem cells (CSCs) resistant to ferroptosis, providing a promised targets to eradicate CSCs through ferroptosis.