bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective inhibitors targeting Fis1/Mid51 protein-protein interactions protect against hypoxia-induced damage in cardiomyocytes
Authors: Zerihun Mulate , Qvit Nir 
Published: December 2023

Cardiovascular diseases (CVDs) are the most common non-communicable diseases globally. An estimated 17.9 million people died from CVDs in 2019, representing 32% of all global deaths. Mitochondria play critical roles in cellular metabolic homeostasis, cell survival, and cell death, as well as producing most of the cell’s energy. Protein–protein interactions (PPIs) have a significant role in physiological and pathological processes, and aberrant PPIs are associated with various diseases, therefore they are potential drug targets for a broad range of therapeutic areas. Due to their ability to mimic natural interaction motifs and cover relatively larger interaction region, peptides are very promising as PPI inhibitors. To expedite drug discovery, computational approaches are widely used for screening potential lead compounds. Here, we developed peptides that inhibit mitochondrial fission 1 (Fis1)/mitochondrial dynamics 51 kDa (Mid51) PPI to reduce the cellular damage that can lead to various human pathologies, such as CVDs. Based on a rational design approach we developed peptide inhibitors of the Fis1/Mid51 PPI. In silico and in vitro studies were done to evaluate the biological activity and molecular interactions of the peptides. Two peptides, CVP-241 and CVP-242 were identified based on low binding energy and molecular dynamics simulations. These peptides inhibit Fis1/Mid51 PPI (-1324.9 kcal mol−1) in docking calculations (CVP-241, -741.3 kcal mol−1, and CVP-242, -747.4 kcal mol−1), as well as in vitro experimental studies Fis1/Mid51 PPI (KD 0.054 µM) Fis1/Mid51 PPI + CVP-241 (KD 3.43 µM), and Fis1/Mid51 PPI + CVP-242 (KD 44.58 µM). Finally, these peptides have no toxicity to H9c2 cells, and they increase cell viability in cardiomyocytes (H9c2 cells). Consequently, the identified inhibitor peptides could serve as potent molecules in basic research and as leads for therapeutic development.
Pharmacokinetics and bioavailability of a new long-acting insulin analog in healthy Chinese volunteers: an open, randomized, single-dose, two-period and two-sequence cross-over study
Authors: Chen Ke-Guang , Zhang Ye-Hui , Ye Pan-Pan , Gao Xue-Hu , Song Lin-Lin , Zhou Hai-Yan , Li Qian , Zhao Fu-Rong , Shi Jin-Yi , Yang Xin-Mei , Shen Kai , Feng Sheng , Zhao Wei 
Published: December 2023

Objectives:INS068 is a novel, soluble, and long-acting insulin analog. In this study, we evaluated the pharmacokinetics and relative bioavailability of two formulations of INS068 in healthy Chinese subjects: a reference formulation packaged in vials and administered via syringe (R), and a test formulation packaged and administered via pen injector (T).Methods:A randomized, open-label, two-period, two-sequence crossover study was conducted with 24 healthy Chinese subjects. Subjects were randomized and administered subcutaneously in the abdomen at 0.4 U/kg of test or reference INS068 injection according to an open crossover design. INS068 concentrations in the serum were measured using LC-MS/MS, and the pharmacokinetic parameters of maximum concentration (Cmax) and area under the concentration-time curve (AUC0–tand AUC0–∞) were used to evaluate relative bioavailability.Results:After a single dose at 0.4 U/kg, the median Tmaxof INS068 was 12 h for both formulations, and the mean t1/2for T and R was 13.0 h and 12.6 h, respectively. The geometric means of Cmaxand AUC0–∞were 3.99 nmol/L and 120 h·nmol/L for the T, and 4.05 nmol/L and 117 h·nmol/L for the R, respectively. The geometric mean ratios of Cmax, AUC0–tand AUC0–∞of T over R were 98.7% (90% CI: 92.7%–105.2%), 102.6% (90% CI: 100.0%–105.3%) and 102.8% (90% CI: 100.1%–105.5%).Conclusion:The overall PK profile of the two formulations of INS068 injection was comparable in healthy subjects, and the pen injector of INS068 had adequate safety and tolerability, supporting it as a new formulation in a phase III study and bridging PK data from early phase clinical trials.Clinical Trial Registration:clinicaltrials.gov, identifier: NCT05336071
An aqueous Commiphora myrrha extract ameliorates paclitaxel-induced peripheral neuropathic pain in mice
Authors: Al-Romaiyan Altaf , Barakat Ahmad , Jose Liny , Masocha Willias 
Published: December 2023

Background: Chemotherapy-induced neuropathic pain (CINP) is a debilitating side effect in individuals undergoing cancer treatment. Treatment of CINP with the current available classes of drugs is limited and often yields unsatisfactory results. Finding therapeutic alternatives of plant origin could provide a new way for the management of CINP. Commiphora myrrha (CM) resin extract has been reported to have anti-inflammatory and analgesic activities, but the effect of CM on neuropathic pain is yet to be investigated in CINP.Objectives: The aim of this study was to investigate the antinociceptive effect of CM extract in a mouse model of paclitaxel-induced neuropathic pain (PINP).Methods: The effects of CM on thermal hyperalgesia and mechanical allodynia were assessed in female BALB/c mice with PINP using a hot plate and a plantar aesthesiometer, respectively. Motor coordination was evaluated using a rotarod apparatus. The involvement of transient receptor potential vanilloid channel 1 (TRPV1) in CM actions was investigated using a capsaicin (a TRPV1 agonist)-induced nociception test. The genetic expression of Trpv1, Nrf2, Sod2, and Hmox1 was assessed using real-time PCR, while protein expression of TRPV1, Iba-1, and CD11b was assessed using Wes™.Results: Administration of CM to mice with established PINP produced a dose-dependent reduction in thermal hyperalgesia. Prophylactic treatment of mice with CM prevented the development of paclitaxel-induced thermal hyperalgesia and mechanical allodynia. CM did not change the motor coordination of mice, as the reaction latency and the rotational velocity of animals pretreated with CM extract were similar to those of animals pretreated with vehicle. CM significantly decreased the number and duration of the flick responses following capsaicin injection into the dorsal surface of the hind paw of mice. The protein expression of TRPV1 was upregulated in the spinal cord of paclitaxel-treated animals compared to vehicle-only-treated control animals, while CM-treated animals had values similar to vehicle-only-treated control animals. The mRNA expression of Nrf2, a major antioxidant transcription factor, was upregulated in the paw skin of mice treated with CM compared to those treated with paclitaxel alone.Conclusion: These results indicate that CM may both treat established and prevent the development of paclitaxel-induced thermal hyperalgesia and mechanical allodynia without any impairment in the motor activity of mice. CM may mediate its action through the peripheral inhibition of TRPV1 channel activity, restoration of normal TRPV1 protein expression in the spinal cord, and elevation of cellular antioxidant defenses. CM has the potential to be used as a therapeutic alternative to treat CINP.
Casuarina glauca branchlets’ extract as a potential treatment for ulcerative colitis: chemical composition, in silico and in vivo studies
Authors: Mohamed Maged E. , El-Shafae Azza M. , Fikry Eman , Elbaramawi Samar S. , Elbatreek Mahmoud H. , Tawfeek Nora 
Published: December 2023

Ulcerative colitis (UC) is an inflammatory bowel disease that is often resistant to current treatment options, leading to a need for alternative therapies. Herbal products have shown promise in managing various conditions, including UC. However, the potential of Casuarina glauca branchlets ethanolic extract (CGBRE) in treating UC has not been explored. This study aimed to analyze the chemical composition of CGBRE and evaluate its efficacy in UC treatment through in silico and in vivo experiments. LC-ESI-MS/MS was used to identify 86 compounds in CGBRE, with 21 potential bioactive compounds determined through pharmacokinetic analysis. Network pharmacology analysis revealed 171 potential UC targets for the bioactive compounds, including EGFR, LRRK2, and HSP90 as top targets, which were found to bind to key CGBRE compounds through molecular docking. Molecular docking findings suggested that CGBRE may be effective in the prevention or treatment of ulcerative colitis mediated by these proteins, where key CGBRE compounds exhibited good binding affinities through formation of numerous interactions. In vivo studies in rats with acetic acid-induced UC demonstrated that oral administration of 300 mg/kg CGBRE for 6 days reduced UC symptoms and colonic expression of EGFR, LRRK2, and HSP90. These findings supported the therapeutic potential of CGBRE in UC and suggested the need for further preclinical and clinical investigation.
The posttraumatic cognitive appraisal inventory (PTCAI): development and validation
Authors: Zhang Wenyue , Yu Wenjing , Wei Baojian , Dong Qianni , Zhang Aihua 
Published: December 2023

ObjectiveThis study aims to develop and validate the Posttraumatic Cognitive Appraisal Inventory (PTCAI) for accidental trauma survivors.MethodBased on interviews and expert feedback, the initial item pool was generated for the Negative Cognitive Appraisal Inventory of Loss and Feeling Threatened, and the Positive Cognitive Appraisal Inventory of Positively Face, Self-Sense, and Relationships. Then, we recruited two groups of accidental trauma survivors to examine the reliability and validity of the PTCAI. Item analysis and exploratory factor analysis (EFA) were conducted on Sample 1. Confirmatory factor analysis (CFA), Pearson correlation analysis, and internal consistency reliability analysis were applied to Sample 2. After 2 weeks, 20 survivors completed the PTCAI again to test temporal stability.ResultsFollowing item analysis, the PTCAI was reduced to 27 items. The results of the EFA demonstrated that the five-factor, 27-item solution of the PTCAI was appropriate, which accounted for 63.931% of the total variation. The CFA indicated that the five-factor second-order model offered an excellent fit to the data. Loss and Feeling threatened were equally important in the study participants’ negative cognitive appraisal of accidental traumas. Self-sence was the most important positive cognitive appraisal of accidental traumas by the study participants. Positively Face and Relationships were somewhat behind. Additionally, the PTCAI demonstrated high concurrent validity and reliability (test–retest and internal consistency).ConclusionThe PTCAI appears to be a reliable and valid instrument for assessing cognitive appraisals of accidental trauma survivors.
Supplementary posterior fusion in patients operated on employing TLIF may decrease the instrumentation failure rate
Authors: Bokov Andrey , Kalinina Svetlana , Khaltyrov Mingiyan , Pavlova Svetlana , Bulkin Anatoliy 
Published: December 2023

BackgroundIt is supposed that additional posterior fusion may provide additional stability of the pedicle screw; however, the clinical impact of additional posterior fusion in patients treated with TLIF remains uncertain. The objective of this study is to assess the clinical efficacy of circumferential fusion in patients treated with TLIF.Materials and methodsThis is a single-center retrospective evaluation of consecutive 179 patients with degenerative lumbar stenosis and instability of spinal segments. Patients with axial pain and neurogenic claudication or radiculopathy associated with spinal stenosis were enrolled during the period from 2012 to 2018. Transforaminal lumbar interbody fusion (TLIF) with a single cage was used to treat patients. In 118 cases a supplementary posterior fusion was made. The duration of follow-up accounted for 24 months, logistic regression analysis was used to assess factors that influence the complication rate.ResultsThe rate of pedicle screw loosening was growing with radiodensity getting decreased and was more frequent in patients with two level fusion. An increase in pedicle screw loosening rate correlated with anterior nonunion Tan 2 and 3 grade while both posterior complete and incomplete fusion resulted in a decline in the complication rate. Lumbosacral fusion, bilateral facet joints` resection and laminectomy turned out to be insignificant factors. The overall goodness of fit of the estimated general multivariate model was χ2 = 87.2230; P &lt; 0.0001. To confirm clinical relevance of those findings, a univariate logistic regression was performed to assess the association between clinically significant pedicle screw instability and posterior fusion in patients operated on employing TLIF. The results of logistic regression analysis demonstrate that additional posterior fusion may decrease the rate of instrumentation failure that requires revision surgery in patients treated with TLIF [B0 = 1.314321; B1 = −3.218279; p = 0.0023; OR = 24.98507; 95% CI (3.209265; 194.5162), the overall goodness of fit of the estimated regression was χ2 = 22.29538, p = &lt;0.0001].ConclusionCircumferential fusion in patients operated on employing TLIF is associated with a decline in the rate of pedicle screw loosening detected by CT imaging and clinically significant instrumentation failure.
Can Comprehensive Medical Reform Improve the Efficiency of Medical Resource Allocation? Evidence From China
Authors: Sun Xiaoyang , Xu Liang , Adnan K. M. Mehedi , Luo Yusen 
Published: December 2023

Objectives: To evaluate the impact of comprehensive medical reform on the efficiency of medical resource allocation in China.Methods: This study employs the Slacks-Based Measure- Directional Distance Function (SBM-DDF) to estimate the efficiency of medical resource allocation (MRAE) in China, using panel data from 30 provinces during 2009–2021. Moreover, a multi-period Difference in differences (DID) model is developed to explore the effect of the comprehensive medical reform pilot (CMRP) strategy on efficiency of medical resource allocation in China.Results: The results show that the average value of China’s medical resources allocation efficiency is 0.861 during the sample period. Coastal area has a higher MRAE than that in the inland area. The DID results show that the comprehensive medical reform pilot strategy has a good, long-lasting impact on the efficiency of medical resource allocation. And the results remain valid after a series of robustness analysis. Additionally, the comprehensive medical reform policy has heterogeneous impact on efficiency of medical resource allocation. The promotion effect is only statistically significant in the eastern and central regions, the groups of higher MRAE and larger population size.Conclusion: China’s comprehensive medical reform policy can effectively promote the improvement of regional efficiency of medical resource allocation.
EFEKTIVITAS KONSUMSI BUAH PEPAYA TERHADAP PENINGKATAN NAFSU MAKAN BALITA
Authors: Farida Yuli , Fariji Achmad , Mardianti Mardianti 
Published: December 2023

Berdasarkan survei Riskesdas 2018, terdapat angka prevalensi gizi buruk dan kurang pada anak usia lima tahun ke bawah sebesar 17,7%. Permasalahan tantangan gizi pada balita tidak dapat dipisahkan dari terjadinya kesulitan makan yang umum terjadi pada kelompok usia ini. Sebuah penelitian yang dilakukan di Jakarta, Indonesia, berfokus pada anak-anak usia prasekolah dan mengungkapkan tingkat prevalensi masalah makan sebesar 33,6%. Menurut Dinas Kesehatan Kabupaten Karawang, 270 bayi dan anak kecil menderita gizi buruk pada tahun 2016. Berbagai penelitian menunjukkan bahwa konsumsi buah pepaya mungkin berdampak positif terhadap nafsu makan. Tujuan penelitian ini adalah untuk mengkaji efektivitas pemberian buah pepaya sebagai sarana meningkatkan nafsu makan balita di Puskesmas Adiarsa yang terletak di Kabupaten Karawang. Penelitian ini menggunakan desain penelitian quasi eksperimen. Kelompok perlakuan mendapat pijat nafsu makan dan buah pepaya dan kelompok kontrol hanya mendapat pijat nafsu makan. Pengamatan selanjutnya dilakukan untuk membandingkan hasil kedua kelompok. Teknik sampling mengunakan purposive sampling, sehingga diperoleh total 116 sampel yang terdiri dari 58 kasus dan 58 kontrol. Uji statistik menggunakan Uji T-Independen. Temuan penelitian menunjukkan bahwa tidak ada perbedaan yang signifikan secara statistik pada rata-rata tingkat nafsu makan antara balita yang mengonsumsi buah pepaya dan yang tidak mengonsumsi buah pepaya (p=0,744). Salah satu rekomendasi bagi peneliti selanjutnya adalah mengatasi potensi variabel perancu untuk memitigasi dampaknya terhadap hasil penelitian. Untuk penelitian selanjutnya, akan lebih baik jika dilakukan standarisasi penyediaan menu makanan untuk meminimalkan pengaruh perbedaan pola makan. Durasi penelitian dapat melebihi satu bulan, yang mencakup kegiatan pemantauan dan evaluasi. Selain itu, penelitian dapat dilakukan secara offline.
EFFECTS OF VARIOUS HOUSING SYSTEMS ON THE DEVELOPMENT OF EQUINE BEHAVIOR IN THOROUGHBRED HORSE PAKISTAN
Authors: Baboo Abdul Saleem Alias , Rajput Muhammad Naeem , Behan Atique Ahmed , Rajput Nasir , Marri Noor -un-Nisa , Tunio Shakeel Ahmed , Siddiqui Shahrood Ahmed 
Published: December 2023

The study was conducted to investigate the impact of various housing systems on the development of equine stereotypies. N=120 x Thoroughbred Pakistan of three different groups (A=40 horses 2years not gelded, B= 40 age 3 years and C= 40 four years gelded) were kept in four distinct types of housing systems, (SHSNI) Single Housing System No Interaction, (SHSLI) Single Housing System Limited Interaction, (DHS) Double Housing System and (GHS) Group Housing. The study was conducted in four phases (Phase-I SHSNI, Phase-II SHSNI, Phase- III DHS and Phase- IVGHS were used) and each phase was comprised of 30 days duration. On every 10th day parameters were recorded, and three readings were recorded in every housing system. A comprehensive set of 12 readings recorded through video recording, personal observation and information provided by horse handlers and randomized complete block design was performed for statistical analysis. Housing systems had significant (p<0.05) impact on the development of stereotypies. The highest incidence of stereotypies 35.83% was found in SHSNI, followed by 29.13% in DHS, 18.31% in GHS and the lowest 16.63% in SHSLI. The maximum number of horses displayed weaving (7.29%), behavior followed by kicking (6.45%), biting (6.03%) and crib-biting (5.83%). The groups (non-gelding and gelding) were found non-significant (p>0.05). The study concludes that SHSLI is more suitable needed to be adopted, system has necessary social interaction, less stereotypies with limited injuries as compared to alternative housing systems.
Prevalência de parasitismo gastrointestinal em cães e gatos de São Miguel do Oeste e avaliação de riscos à saúde humana e animal
Authors: Buzatti Andréia , Pissatto Jéssica Decker , Guarangni Leticia Zanin , Da Silva Maria Eduarda Rodrigues 
Published: December 2023

O presente estudo teve como objetivo estabelecer o diagnóstico laboratorial e avaliar a prevalência de parasitos gastrointestinais e de ectoparasitos em cães e gatos oriundos da rotina de atendimento clínico da CLINIVET – Clínica Veterinária da Universidade do Oeste de Santa Catarina - UNOESC, Campus de São Miguel do Oeste. Além disso, também avaliar o parasitismo por agentes com potencial zoonótico, os quais podem apresentar riscos para a saúde pública. Durante os anos de 2018 a 2022 foram analisadas ao todo 178 amostras de fezes de cães e gatos e 48 amostras de cães para pesquisa de ectoparasitos. Das amostras de fezes, 65 (36,51%) foram de felinos e 113 (63,48%) foram de caninos. Os resultados demonstraram maior prevalência das espécies: Ancylostoma caninum e cati (23,68%), Cystoisospora spp. (32,89%), Giardia spp. (11,84%), Trichuris vulpis (9,21%), Toxocara cati e T. canis (10,52%) e amostra sugestiva para Toxoplasma gondii (11,84%). Na pesquisa de ectoparasitos foi possível observar a presença de Sarcoptes scabiei, Demodex canis e o carrapato Rhipicephalus sanguineus. Os resultados observados ressaltam que o controle destes agentes é fundamental para a sanidade dos animais e reforçam a necessidade de medidas de controle parasitário adequado, assim como, de orientar a população acerca do assunto.
El investigador educativo frente a las acciones acordes a las sociedades de hoy
Authors: García-Perea María Dolores 
Published: December 2023

Las sociedades de hoy están en continua transformación. Por ello, los actores educativos, en especial, el investigador identifique, elija y desarrolle las acciones que requiere la sociedad, sin omitir las generadas en otros periodos históricos. Lamentablemente, existen tanto investigadores como autoridades institucionales y educativos que desconocen las acciones acordes a esta época histórica y, quienes las identifican, en ocasiones las ignoran por la ausencia de apoyos institucionales para llevarlas a cabo o deciden cubrir los gastos económicos de manera personal para desarrollarlas según sus convicciones. Ante estas situaciones, en el presente trabajo se identifica las acciones, acordes a las sociedades actuales y las realizadas por tres investigadoras que laboran en instituciones educativas de posgrado ubicadas en distintos estados de la república mexicana. La investigación realizada es cualitativa, con referente teórico y empírico. Se privilegia el análisis interpretativo y crítico, el enfoque situacional, la intencionalidad prospectiva, el estudio de caso y está orientada hacia la biográfica profesional. Entre las conclusiones se encuentran: aún de los pocos o nulos apoyos económicos, tecnológicos, humanos y materiales, las informantes del trabajo, reconocen, eligen y desarrollan algunas de las nuevas acciones por convicción y ética profesional, sin descartar las asignadas en el momento de su contratación laboral.
Comparação físico-química e avaliação antioxidante de méis de abelhas jataí (Tetragonisca angustula) e africanizada (Apis mellifera L.) produzidos no município de Joinville-SC
Authors: Da Silva Tainara Luciano , Schroeder Gabriela Sangalli , Venâncio Stefany de Mira , Milarch Carine de Freitas 
Published: December 2023

O mel consiste em uma solução sobressaturada de açúcares, produzido por abelhas melíferas a partir do néctar das flores. Possui alto grau de complexidade em sua composição, e até o momento já foram encontradas 181 substâncias distintas. O presente estudo realizou uma comparação das análises físico-químicas e capacidade antioxidante total entre amostras de méis de abelhas africanizadas (Apis mellifera L.) e de abelhas sem ferrão Jataí (Tetragonisca angustula) de amostras obtidas na cidade de Joinville-SC. Foi possível observar que o mel de abelha nativa apresentou 73,68% de açúcares totais, enquanto que o mel de abelhas africanizadas foi de 63,78%. Já o teor de açúcares redutores obtidos para A. mellifera foi de 59,97%, enquanto que para T. Angustula foi de 70,08%, assim as amostras de méis de abelhas africanizadas mostra-se fora do valor estabelecido pela Legislação Brasileiras sobre qualidade de méis, na qual determina que o mel deve apresentar no mínimo 65% de açúcares redutores, ou seja, 65g/100g de mel. No entanto, foi observado que a capacidade antioxidante total nos méis de abelhas nativas (18,53 µmol/L) foi superior quando comparado com os méis de abelhas africanizadas (10,76 µmol/L). Embora foi observada diferenças entres os valores para hidroximetilfurfural (HMF) do mel de abelhas jataí (18,6 mg/kg) e africanizada (23,3 mg/kg), os valores ficaram dentro do limite aceitável para este parâmetro. Assim, o presente estudo evidenciou que há diferenças entre os méis das duas abelhas, e que de forma muito relevante, o mel das abelhas nativas apresentou capacidade antioxidante total superior do que o mel de abelhas exóticas, evidenciando a necessidade de mais estudos aprofundando esta temática.