bluuebunny/crossref_metadata_2025 huggingface dataset:
Análisis financiero de la cartera de crédito de la Cooperativa de Ahorro y Crédito CACPE Biblián y su impacto frente a la emergencia sanitaria en el año 2019-2020
Authors: Peralta Sarmiento Esthela Guadalupe , Becerra Molina Edison
Published: March 2023

La pandemia del Covid-19 incidió de manera negativa en el desempeño económico del Ecuador, las estadísticas del Banco Central estimaron la caída del Producto Interno Bruto al 7,8% para el año 2020, en el contexto del sector financiero se resalta la disminución del 23,4% de las operaciones de crédito de consumo concedidas por el sistema privado y las instituciones de la economía popular y solidaria, además del decremento en la intermediación financiera, reducción de las utilidades y el deterioro de la cartera de crédito, en este sentido el objetivo de este artículo es realizar un análisis financiero de la cartera de crédito de la Cooperativa de Ahorro y Crédito CACPE Biblián, para determinar el impacto de la emergencia sanitaria en el período económico 2019-2020, mediante la aplicación de sistema de monitoreo PERLAS, cuya práctica se distingue como las mejores en la gestión cooperativa a nivel mundial. Se aplicó una investigación de tipo descriptivo y propositivo enfocado en el análisis financiero cuantitativo y cualitativo. Los resultados demuestran evidencian en el año 2020 un pequeño incremento de los activos improductivos con respecto a la meta establecida por PERLAS, debido a la contracción de los créditos por los efectos del Covid-19, que implica un mayor margen de provisiones ante la eventualidad de un riesgo crediticio y un menor margen de rendimiento. Como conclusión se puede manifestar la adecuada gestión de los directivos de la cooperativa en la adopción oportuna de las medidas de alivio financiero aprobadas por la Junta Monetaria para el diferimiento de créditos y evitar que los mismos pasen a vencidos durante los meses de afectación de la pandemia y de esta manera, a nivel de estados financieros mitigar sus efectos en la calidad de la cartera de crédito, en el periodo sujeto al estudio.
Análisis de correspondencia múltiple entre el tamaño de las empresas y su participación económica en el Estado de México
Authors: Puebla Maldonado Armando
Published: March 2023

La presente investigación tiene como propósito el análisis económico regional que coadyuve en el diagnóstico de la planeación sectorial del Estado de México. Para cumplir con este propósito se buscó determinar el nivel de asociación entre el tamaño de las unidades económicas y un conjunto de variables representativas de la actividad económica. Se partió de la metodología de minería de datos para aplicar de manera cuantitativa y descriptiva la metodología del Análisis de Correspondencia Múltiple (ACM). Los resultados sugieren,  que hay un nivel de asociación positiva moderada alrededor del 50 % en dos de sus indicadores: El coeficiente de asociación de Pearson es de 0.4685 y el de Mathews con 0.5303. Sin embargo, en los indicadores V de Cramer y de Inercial Total fueron correlaciones positivas débiles respectivamente de 0.3062 y 0.2812. Ante esta situación se propuso como medida alternativa el análisis discriminante y el de varianza, los cuales arrojaron que las microempresas están más asociadas con el Personal Ocupado Total (POT) y la Producción Bruta Total (PBT). Por su parte, el Valor Agregado Censal Bruto (VACB) e Ingreso por Suministros de Bienes y Servicios (ISBB) con medianas y grandes empresas. Asimismo, la prueba Chi-Cuadrado, además de que comprobó que los datos son estadísticamente significativos al 95 %, también apoyo la hipótesis de una asociación entre el tamaño de las unidades económicas y las variables de Participación Económica. Los resultados abonan a que las políticas públicas deberían considerar la heterogeneidad de la planta productiva y su participación económica.
Pelatihan Penggunaan Educandy Sebagai Game Edukatif Di Sd Muhammadiyah 08 Plus Jakarta Timur
Authors: Rahmanto Muhammad Arifin , Bunyamin Bunyamin , Noviyanti Kiky
Published: March 2023

Dalam Proses Pembelajaran, tentunya seorang guru harus mempersiapkan media  agar para peserta didik mudah memahami materi yang dapat meningkatkan hasil belajar mereka dan tercapainya tujuan dalam pendidikan. Tantangan seorang guru adalah menciptakan suasana belajar yang tidak membosankan agar pada saat proses pembelajaran berlangsung mampu memitigasi peserta didik yang kurang melibatkan diri secara aktif dan cenderung pasif.  Begitupun guru harus memahami bahwa untuk mengevaluasi pembelajaran tidak selalu  dengan cara ujian atau menjawab latihan soal yang memiliki kesan monoton dan membosankan. Umumnya, pengevaluasian terhadap peserta didik berbentuk soal PG dan Esai saja, sehingga bentuk evaluasi yang digunakan  kurang menarik para peserta didik. Dari permasalahan diatas, Solusi yang ditawarkan adalah dengan memberikan Pelatihan penggunaan Educandy sebagai Game Edukasi di SD Muhammadiyah 8 Plus Jakarta. Aplikasi ini merupakam game edukasi yang dapat membuat pembelajaran menjadi bervariasi dan menyenangkan. Sehingga, peserta didik tidak merasa bosan dan termotivasi untuk belajar lebih giat lagi. Pelatihan ini bertujuan untuk meningkatkan kemampuan guru-guru dalam mengajarkan suatu materi terhadap peserta didik dan mengevaluasinya. Sehingga, pembelajaran akan berjalan lebih efektif dan menjadikan guru lebih professional. Kegiatan pelatihan ini, nantinya akan berlangsung secara Offline lebih difokuskan kepada seorang guru dengan metode diskusi panel dan praktek langsung dalam pemanfaatan Game Educandy.Kata Kunci: Media, Educandy, evaluasi
Developing Teaching Materials based on Digital Visual Literacy
Authors: Faridha Noor , Adisiswanto Alissa Ernawati , Rahma Vina
Published: March 2023

The aims of this study were to: (1) provide teaching materials for students of State Administration, FISIP, and UMSJ in the form of English language modules; and (2) determine the feasibility of teaching materials in the form of English language modules. Research and Development (R&D) research designs, or research that is utilized to create specific goods and evaluate their viability. This research is a research development project (Research and Development). The four-D (4D) development model is the basis for the research design, which has four key stages: (1) define; (2) design; (3) develop, and (4) deploy. In this study, questionnaires and focus group discussions (FGD) were used to collect data. In learning, having access to educational resources is very important. This is because this teaching material contains information about English for Special Purposes courses offered by the State Administration Study Program, FISIP, and UMSJ. Based on preliminary observations made in the speaking class of semester 1 students of the State Administration Study Program at Moch Sroedji University, several deficiencies were found in terms of teaching English speaking: (1) the lecturer's speaking teaching method was less varied (2) the lecturer did not use appropriate media/techniques the theme to be discussed in the speaking course; and (3) learning to speak seems monotonous and boring. Increasing literacy through digital visual literacy is one way to work around this. This ability can be developed with the help of visual media literacy. Researchers adapted the model (Gall, 2003) in this study, which includes needs analysis, product development, expert validation, revision, and testing and modification. At the needs analysis stage, researchers conducted interviews with lecturers and students. Based on the results of the needs analysis, they need literacy and strategies to help them improve their speaking skills.
Improving immunotherapy for breast cancer patients
Authors:   , Voorwerk Leonie
Published: March 2023

In this thesis, we aimed to explore short-term immune induction treatments to prime breast tumors for immunotherapy response and to investigate immune responses in breast cancer for improved patient selection. In the TONIC-trial, a two-week induction treatment with low-dose chemotherapy or irradiation, most notably doxorubicin or cisplatin, followed by immunotherapy was able to induce clinical and immunological responses in patients with metastatic triple-negative breast cancer (no expression of the hormone receptor; TNBC). Comprehensive examination of tumor biopsies and blood samples from these patients revealed that eosinophils, a type of immune cell typically involved in allergic reactions, were strongly increased in the blood and tumors of TNBC patients responding to immunotherapy. Using mouse models, we demonstrate that eosinophils are an essential link between other immune cells to induce immunotherapy responses. In the GELATO-trial, we investigated the clinical efficacy of twelve weeks of low-dose carboplatin in combination with immunotherapy in patients with metastatic lobular breast cancer and found this regimen to be mainly effective in patients with triple-negative lobular breast cancer. Furthermore, we demonstrate that breast tumors with low or moderate expression of the hormone receptor have comparable immunological characteristics as TNBC, thereby potentially identifying a subgroup that might benefit from immunotherapy. In summary, in this thesis we have identified new avenues that can be used to further investigate rationale immunotherapy combinations in breast cancer and to explore potential biomarkers for immunotherapy response.
Features of creating fast-growing and multifunctional field-protecting forest strips in the Forest-Steppe zone of Ukraine
Authors: Solomakha I. , Sabluk W , Gumentyk M. , Solomakha V.
Published: March 2023

To ensure the maximum protection of agricultural crops from climatic factors unfavorable for their growth and development, it is necessary to create an optimal number of field protection forest strips. In particular, for the Forest-Steppe zone of Ukraine, less than half of the optimal needs are available, which indicates an urgent need for their additional creation. The expediency of creating fast-growing and multifunctional field forest strips is substantiated, and the productivity of new bioenergy crops during their formation for use in beekeeping and as biofuel is determined. For this purpose, a model of the artificial formation of a forest strip with its possible further exploitation is proposed. The most optimal one is to develop the concept of creating field forest strips with the use of multifunctional tree species, which, in addition to the function of wind, water and dust retention, will also perform other economic tasks. In particular, along with their intended purpose, they can be used as raw materials for biofuel production and as early honey plants. For the accelerated creation of field protection forest strips, it is advisable to use mixed 6–8- row plantings, where the middle 2–3 rows are planted with the involvement of tree species, including the use of species valuable as raw materials for beekeeping. These forest strips are complemented on both sides by planted strips of energy crops, which are important for beekeeping and are a valuable resource for obtaining fuel raw materials. For this purpose, it is advisable to plant 10–12 thousand pieces on one hectare poplar cuttings (Populus sp.), 1250 pieces of paulownia plants (Paulownia tomentosa Steud.) with a row width of 2×4 m and 17–18 thousand pieces cuttings of energy willow (Salix viminalis L.). It is also possible to replace part of the poplar cuttings with cuttings of common robinia (Robinia pseudoacacia L.) and linden (Tilia cordata Mill.). The creation of such plantations near settlements will contribute to their significant use of raw materials and will be quite effective in carrying out their main function of ecological stabilization of agro-landscapes.
Invasive species of the flora of transformed sections of railway tracks in the bottom of the Dnister–Tiligul river
Authors: Bondarenko О.
Published: March 2023

In order to study invasive species as dangerous elements of foreign flora, modern monitoring studies are needed under the conditions of various ecotopes of a wide range of their transformation. According to the «Strategy of biosecurity and biological protection», alien species are a threat to biodiversity at its various levels. Taking into account that railway tracks are one of the main ways of penetration and initial establishment of synanthropic species in new territories, in 2018–2021, the flora of the tracks in the areas of the Dniester floodplain was studied. 34 invasive species from 14 families were noted, they included Asteraceae (26.47% of species), Brassicaceae and Poaceae (17.65% each), Amaranthaceae (8.82%) and others. The majority of species (55.88%) grows both on track sections and (in addition) next to ruderalized sections of overburden. Another 11 species (32.35%) can be found on tracks, ruderalized areas of overburden and on the roadsides of the nearby highway. Only two species (5.88%) are cultivated. Two more species such as Amaranthus powellii S.Watson, Oxybaphus nyctagineus (Michx.) Sweet are noted only on railway tracks and sections of railway infrastructure. According to the life form, nine species (26.47%) are hemicryptophytes. 23 ones are therophytes (67.65%). Two species are fanerophytes (5.88%). According to the chronotype, 41.18% of the species are aschaeophytes. Kenophytes make 58.82%. Among archaeophytes, most plant species have a frequency of occurrence — «scattered» and «abundant» (35.71% each). Among the kenophyres, there are the most species whose plants were «scattered» (40.00%). In general, the majority of invasive species, by frequency of occurrence, belong to the «scattered» (38.25%) and «abundant» (23.53%) categories. Also there are «single» (17.65%), «usually» (11.77%), «single locality» (8.82%). Most species (70.60%) are represented by wide ranges: cosmopolitan (and hemi-cosmopolitan) make 44.12%, Eurasian form 14.71%, Euro-American make 11.77%. Eight species (23.53%) are particularly dangerous for the environment, as they are transformers of local growth. Most of the plants of invasive species of railway tracks were also found on adjacent ruderalized areas. Therophytes, kenophytes and species with a wide range prevail. They are found, mostly «scattered» and «abundant». Eight species (23.53%) are the most dangerous for environment, because they transform ground place (Ambrosia artemisiifolia, Centaurea diffusa, Conyza canadensis, Grindelia squarrosa, Iva xanthiifolia, Elaeagnus angustifolia, Anisantha tectorum, Setaria glauca).
Kintsugi; Exploring the form-giving potential of knit-bacterial cellulose biocomposites in the context of footwear.
Authors: De Lara Carolina
Published: March 2023

Present times are ablaze with environmental change, with fashion being no stranger to controversy as it struggles not only with keeping up with market demand, but making material production more efficient. Living materials and biocomposites, due to being easy, relatively inexpensive and quick to produce offer a biodegradable alternative to traditional, non-reusable materials, particularly in the fields of footwear and accessories, which demand a wider scope of textures and component types. 'Kintsugi' speculates how bacterial cellulose in combination with knitted structures can occupy a prominent place in fashion and design thinking by visually discussing the morphology and role of volume as conforming components intended to develop footwear prototypes. By including stiff elements into the concept narrative, what is object and dress is challenged and offers an insight into what they could be and how they could become, as well as questioning existing making methods.
Inflammation in Major Depressive Disorder Patients with and without Attempted Suicide
Authors: TAŞCI Gülay , ÖZSOY Filiz
Published: March 2023

Objective: This study aimed to examine Major Depressive Disorder (MDD) patients with or without attempted suicide history for inflammation parameters.

Methods: The study included 287 participants, 187 had MDD diagnosis (87 patients with a suicide attempt, 100 patients without suicide history) and 100 healthy. All participants were subjected to Beck Depression Inventory (BDI).

Results: Mean BDI score of MDD patients with suicide attempts was higher than the other two groups (p
Nanomedicine in Lung Cancer Immunotherapy
Authors: Doroudian Mohammad , Zanganeh Saba , Abbasgholinejad Elham , Donnelly Seamas C.
Published: March 2023

Lung cancer is the major cause of cancer death worldwide. Cancer immunotherapy has been introduced as a promising and effective treatment that can improve the immune system’s ability to eliminate cancer cells and help establish immunological memory. Nanoparticles can contribute to the rapidly evolving field of immunotherapy by simultaneously delivering a variety of immunological agents to the target site and tumor microenvironment. Nano drug delivery systems can precisely target biological pathways and be implemented to reprogram or regulate immune responses. Numerous investigations have been conducted to employ different types of nanoparticles for immunotherapy of lung cancer. Nano-based immunotherapy adds a strong tool to the diverse collection of cancer therapies. This review briefly summarizes the remarkable potential opportunities for nanoparticles in lung cancer immunotherapy and its challenges.
The impact of microbiome dysbiosis on T cell function within the tumor microenvironment (TME)
Authors: DiPalma Michelle P. , Blattman Joseph N.
Published: March 2023

Insights into the effect of the microbiome’s composition on immune cell function have recently been discerned and further characterized. Microbiome dysbiosis can result in functional alterations across immune cells, including those required for innate and adaptive immune responses to malignancies and immunotherapy treatment. Dysbiosis can yield changes in or elimination of metabolite secretions, such as short-chain fatty acids (SCFAs), from certain bacterial species that are believed to impact proper immune cell function. Such alterations within the tumor microenvironment (TME) can significantly affect T cell function and survival necessary for eliminating cancerous cells. Understanding these effects is essential to improve the immune system’s ability to fight malignancies and the subsequent efficacy of immunotherapies that rely on T cells. In this review, we assess typical T cell response to malignancies, classify the known impact of the microbiome and particular metabolites on T cells, discuss how dysbiosis can affect their function in the TME then further describe the impact of the microbiome on T cell-based immunotherapy treatment, with an emphasis on recent developments in the field. Understanding the impact of dysbiosis on T cell function within the TME can carry substantial implications for the design of immunotherapy treatments and further our understanding of factors that could impact how the immune system combats malignancies.
Minimally invasive closure of a progressive pseudoaneurysm of the ascending aorta: A case report
Authors: Wu Yuan , Fan Linglin , Liu Fei , Zhuang Hui , Wu Xijie
Published: March 2023

Ascending aortic pseudoaneurysm (AAP) is rare but may cause life-threatening complications. Although the placement of a stent graft and the use of occluder devices and vascular plugs to exclude pseudoaneurysm are adopted for some patients, the management of progressive pseudoaneurysms that may rupture at any time remains a challenge that needs to be addressed. In this study, we present the case of a patient with an AAP that was caused by aortic and mitral valve replacement for the giant left ventricle. Aortic pseudoaneurysm was suspected on the basis of a spherical cystic echo (70 × 80 mm) of the ascending aorta; this pseudoaneurysm was detected by an ultrasonic cardiogram, and the diagnosis was confirmed by an aortic computed tomography angiography (CTA) examination. To prevent the unexpected rupture of a progressive pseudoaneurysm, our patient was treated with a 28- mm ASD occluder without any procedural complications. Our patient has a good prognosis, which will inspire clinicians to choose minimally invasive procedures when dealing with such high-risk cases in emergency situations.
Design of a wireless charging system in DC microgrids with accurate output regulation and optimal efficiency
Authors: Li Chenchen , Wang Kaiyuan , Mao Yuan
Published: March 2023

This paper presents a general circuit and control design method for wireless power transfer (WPT) systems in DC microgrids to achieve optimal power transfer efficiency, while maintain accurate output voltage regulation. An auxiliary inductor is added at the transmitter resonator to form a current sink to ensure zero voltage switching (ZVS) of the primary-side full-bridge inverter with even extreme-light load conditions. Besides, an adaptive proportional-integral (PI) controller is adopted to track the output voltage references by regulating the phase shift angle of the phase shift control for the full-bridge inverter. The coefficients of the adaptive proportional-integral controller are determined by the inductor of the auxiliary inductor. Both simulation and experimental results have validated the effectiveness of the proposed circuit and control design in achieving optimal efficiency and output voltage regulation for wireless power transfer systems in DC microgrids with source and load variations.
Throughout in vitro first spermatogenic wave: Next-generation sequencing gene expression patterns of fresh and cryopreserved prepubertal mice testicular tissue explants
Authors: Dumont Ludovic , Lopez Maestre Hélène , Chalmel Frédéric , Huber Louise , Rives-Feraille Aurélie , Moutard Laura , Bateux Frédérique , Rondanino Christine , Rives Nathalie
Published: March 2023

Introduction

Suitable cryopreservation procedures of pre-pubertal testicular tissue associated with efficient culture conditions are crucial in the fields of fertility preservation and restoration. In vitro spermatogenesis remains a challenging technical procedure to undergo a complete spermatogenesis.The number of haploid cells and more specifically the spermatic yield produced in vitro in mice is still extremely low compared to age-matched in vivo controls and this procedure has never yet been successfully transferred to humans.

Methods

To evaluate the impact of in vitro culture and freezing procedure, pre-pubertal testicular mice testes were directly cultured until day 4 (D4), D16 and D30 or cryopreserved by controlled slow freezing then cultured until D30. Testes composed of a panel of 6.5 dpp (days postpartum), 10.5 dpp, 22.5 dpp, and 36.5 dpp mice were used as in vivo controls. Testicular tissues were assessed by histological (HES) and immunofluorescence (stimulated by retinoic acid gene 8, STRA8) analyses. Moreover, a detailed transcriptome evaluation study has been carried out to study the gene expression patterns throughout the first in vitro spermatogenic wave.

Results

Transcriptomic analyses reveal that cultured tissues expression profiles are almost comparable between D16 and D30; highlighting an abnormal kinetic throughout the second half of the first spermatogenesis during in vitro cultures. In addition, testicular explants have shown dysregulation of their transcriptomic profile compared to controls with genes related to inflammation response, insulin-like growth factor and genes involved in steroidogenesis.

Discussion

The present work first shows that cryopreservation had very little impact on gene expression in testicular tissue, either directly after thawing or after 30 days in culture. Transcriptomic analysis of testis tissue samples is highly informative due to the large number of expressed genes and identified isoforms. This study provides a very valuable basis for future studies concerning in vitro spermatogenesis in mice.
Extended state observer-based predictive control for soft open point
Authors: Wang Zhengqi , Lu Peng , Zhou Haoyu , Chen Li
Published: March 2023

This paper proposes an extended state observer-based ultra-local model-free three-vector predictive control method for Soft Open Point (SOP). First, the Ultra-Local Model-Free Predictive Control (ULMFPC) method is proposed to improve the robustness of the system, which only uses the input and output of the outer-loop, and any other parameters are not involved. Second, considering parameter perturbations and external disturbances in the SOP system, an expansion state observer (ESO) is established to observe the SOP system’s total perturbations and the perturbations are compensated in real-time to improve the system. Third, to solve the problem of significant current harmonics in traditional model predictive control (MPC), a three-vector MPC method (TV-MPC) is adopted to reduce the total harmonic distortion rate (THD) of the current. Finally, it is verified by simulation that the proposed method can effectively reduce the current harmonics of the SOP system, rate value setting time, and improve the dynamic performance effectively. When perturbations occur in the system, the proposed method can improve the anti-interference and robustness of the system.
Research on the application of improved NSGA-II in the structure design of wind turbine blade spar cap
Authors: Chen Cheng , Wang Long , Niu Muhua
Published: March 2023

Introduction: The blade is one of the most important parts of a wind turbine. Blade design is a complicated process involving many design links and mutual couplings. To efficiently obtain the Pareto Front and optimal blade, a novel methodology combined the improved NSGA-II with Thin-Walled Beam Theory and Classic Laminated Theory has been developed.

Methods: In the optimization study, the design parameters are the thickness distribution of the spar cap and a parametric model based on blade production process is developed. The objective function is on the minimization of mass and the maximization of flap-wise stiffness. As a practical engineering application research, a 15 MW wind turbine IEA-15-240-RWT developed by NREL is used as a reference model.

Results: Laws on the number of variables, blade profiles, design loads and natural frequencies present in the design have been studied through Pareto fronts obtained from multi-objective optimization results.

Discussion: These laws have important implications for practical engineering design work. Meanwhile, the results show that the new methodology is effective for blade structure design, and that this approach can be easily extended to study the design of influence laws for more design parameters or more complex blade design problems.
Using content and comparative analysis to contextualize the criteria for urban resiliency planning from international and US cities perspectives
Authors: Applegate Joshua D. , Tilt Jenna H.
Published: March 2023

This study focuses on how the term “urban resiliency” and other related terms are operationalized across spatial scales. The European Union and United Nations established international goals, targets, and the specific measurable indicators with both theEuropean Green Dealand their2030 Sustainable DevelopmentGoals (SDGs) to address climate change, with overarching goals of becoming the world’s first carbon neutral continent. Much of this work to “green” cities falls under the concepts of urban resiliency, Green Infrastructure (GI), and ecosystem services (ES). This study seeks to understand the criteria considered for planning, development, implementation and maintenance urban resiliency at city and international levels. By contextualizing and clarifying broad terms likeresiliency,ecosystem services, andGreen Infrastructurefor planners, politicians, and people within communities, our comparative analysis provides detailed understanding of the similarities and differences between plans from a national perspective, along with analysis of city-to-city comparisons. Our results suggest there are differences in focus regarding key aspects of resiliency, as well as the strategies suggested for resilient cities. Key differences were found in the importance placed on transportation, the future role of Green Infrastructure, and definitions of ecosystem services. These differences may have potential impacts on outcomes for resiliency project development and maintenance.
Impacts of vitrification on the transcriptome of human ovarian tissue in patients with gynecological cancer
Authors: Gu Ruihuan , Ge Naidong , Huang Bin , Fu Jing , Zhang Ying , Wang Ningyi , Xu Yan , Li Lu , Peng Xiandong , Zou Yaoyu , Sun Yijuan , Sun Xiaoxi
Published: March 2023

Objective: This study investigated the effects of a vitrification/warming procedure on the mRNA transcriptome of human ovarian tissues.

Design: Human ovarian tissues were collected and processed through vitrification (T-group) and then subjected to RNA sequencing (RNA-seq) analysis, HE, TdT-mediated dUTP nick-end labeling (TUNEL), and real-time quantitative PCR, and the results were compared to those of the fresh group (CK).

Results: A total of 12 patients, aged 15–36 years old, with a mean anti-Müllerian hormone level of 4.57 ± 3.31 ng/mL were enrolled in this study. According to the HE and TUNEL results, vitrification effectively preserved human ovarian tissue. A total of 452 significantly dysregulated genes (|log2FoldChange| > 1 and p < 0.05) were identified between the CK and T groups. Among these, 329 were upregulated and 123 were downregulated. A total of 372 genes were highly enriched for 43 pathways (p < 0.05), which were mainly related to systemic lupus erythematous, cytokine–cytokine receptor interaction, the TNF signaling pathway, and the MAPK signaling pathway. IL10, AQP7, CCL2, FSTL3, and IRF7 were significantly upregulated (p < 0.01), while IL1RN, FCGBP, VEGFA, ACTA2, and ASPN were significantly downregulated in the T-group (p < 0.05) compared to the CK group, which agreed with the results of the RNA-seq analysis.

Conclusion: These results showed (for the first time to the authors’ knowledge) that vitrification can induce changes in mRNA expression in human ovarian tissues. Further molecular studies on human ovarian tissues are required to determine whether altered gene expression could result in any downstream consequences.
Understanding protein import in diverse non-green plastids
Authors: Christian Ryan , Labbancz June , Usadel Bjorn , Dhingra Amit
Published: March 2023

The spectacular diversity of plastids in non-green organs such as flowers, fruits, roots, tubers, and senescing leaves represents a Universe of metabolic processes in higher plants that remain to be completely characterized. The endosymbiosis of the plastid and the subsequent export of the ancestral cyanobacterial genome to the nuclear genome, and adaptation of the plants to all types of environments has resulted in the emergence of diverse and a highly orchestrated metabolism across the plant kingdom that is entirely reliant on a complex protein import and translocation system. The TOC and TIC translocons, critical for importing nuclear-encoded proteins into the plastid stroma, remain poorly resolved, especially in the case of TIC. From the stroma, three core pathways (cpTat, cpSec, and cpSRP) may localize imported proteins to the thylakoid. Non-canonical routes only utilizing TOC also exist for the insertion of many inner and outer membrane proteins, or in the case of some modified proteins, a vesicular import route. Understanding this complex protein import system is further compounded by the highly heterogeneous nature of transit peptides, and the varying transit peptide specificity of plastids depending on species and the developmental and trophic stage of the plant organs. Computational tools provide an increasingly sophisticated means of predicting protein import into highly diverse non-green plastids across higher plants, which need to be validated using proteomics and metabolic approaches. The myriad plastid functions enable higher plants to interact and respond to all kinds of environments. Unraveling the diversity of non-green plastid functions across the higher plants has the potential to provide knowledge that will help in developing climate resilient crops.
Characterization of dysbiosis of the conjunctival microbiome and nasal microbiome associated with allergic rhinoconjunctivitis and allergic rhinitis
Authors: Wang Yuan , Li Xuan , Gu Shuntong , Fu Junhong
Published: March 2023

Background

Allergic rhinoconjunctivitis (ARC) and allergic rhinitis (AR) are prevalent allergic diseases. People are becoming increasingly aware of the impact of microbial disorders on host immunity and allergic diseases. Studies have demonstrated an association between allergic diseases and the microbiome, but much remains unknown. We assessed changes in the conjunctival microbiome and nasal microbiome in patients with ARC or AR.

Methods

Conjunctival swabs and nasal swabs were collected from each participant for 16S rRNA amplicon sequencing. Bacterial communities were analyzed.

Results

Forty patients with ARC, 20 patients suffering from AR, and 34 healthy controls (HCs) were recruited. This study found the abundance of conjunctival microbiome in patients with ARC or AR was significantly lower than that in HCs. The diversity of conjunctival microbiome in patients with AR was significantly lower than those in the other two groups. There is no significant difference in abundance of nasal microbiome between the three groups. The diversities of nasal microbiome in patients with ARC or AR were significantly lower than that in HCs. We found significant differences in microbiota compositions in patients with ARC or AR compared with those in HCs. However, no significant difference in microbiota compositions was found between patients with ARC and patients with AR. Microbiome functions in the ARC group and AR group were also altered compared with HCs.

Conclusions

We revealed changes in the composition and function of the conjunctival microbiome and nasal microbiome of patients with ARC or AR, which suggests that there is a relationship between allergic conditions and the local microbiome.
Anti-cyclooxygenase, anti-glycation, and anti-skin aging effect of Dendrobium officinale flowers’ aqueous extract and its phytochemical validation in aging
Authors: Zhou Huiji , Zhou Luxian , Li Bo , Yue Rongcai
Published: March 2023

Introduction

Dendrobium officinale Kimura et Migo (D. officinale) , widely called as “life-saving immortal grass” by Chinese folk, is a scarce and endangered species. The edible stems of D. officinale have been extensively studied for active chemical components and various bioactivities. However, few studies have reported the well-being beneficial effects of D. officinale flowers (DOF). Therefore, the present study aimed to investigate the in vitro biological potency of its aqueous extract and screen its active components.

Methods

Antioxidant tests, including 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), the ferric reducing ability of plasma (FRAP), and intracellular reactive oxygen species (ROS) level analyses in primary human epidermal keratinocytes, anti-cyclooxygenase2 (COX-2) assay, anti-glycation assay (both fluorescent AGEs formation in a BSA fructose/glucose system and glycation cell assay), and anti-aging assay (quantification of collagen types I and III, and SA-β-gal staining assay) were conducted to determine the potential biological effects of DOF extracts and its major compounds. Ultra-performance liquid chromatography-electrospray ionisation-quadrupole-time-of-flight-mass spectrometry (UPLC-ESI-QTOF-MS/MS) was performed to investigate the composition of DOF extracts. Online antioxidant post-column bioassay tests were applied to rapidly screen major antioxidants in DOF extracts.

Results and discussion

The aqueous extract of D. officinale flowers was found to have potential antioxidant capacity, anti-cyclooxygenase2 (COX-2) effect, anti-glycation potency, and anti-aging effects. A total of 34 compounds were identified using UPLC-ESI-QTOF-MS/MS. Online ABTS radical analysis demonstrated that 1-O-caffeoyl-β-D-glucoside, vicenin-2, luteolin-6-C-β-D-xyloside-8-C-β--D-glucoside, quercetin-3-O-sophoroside, rutin, isoquercitrin, and quercetin 3-O-(6″-O-malonyl)-β-D-glucoside are the major potential antioxidants. In addition, all selected 16 compounds exerted significant ABTS radical scavenging ability and effective AGE suppressive activities. However, only certain compounds, such as rutin and isoquercitrin, displayed selective and significant antioxidant abilities, as shown by DPPH and FRAP, as well as potent COX-2 inhibitory capacity, whereas the remaining compounds displayed relatively weak or no effects. This indicates that specific components contributed to different functionalities. Our findings justified that DOF and its active compound targeted related enzymes and highlighted their potential application in anti-aging.
Role of the PADI family in inflammatory autoimmune diseases and cancers: A systematic review
Authors: Zhu Changhui , Liu Chunyan , Chai Zhengbin
Published: March 2023

The peptidyl arginine deiminase (PADI) family is a calcium ion-dependent group of isozymes with sequence similarity that catalyze the citrullination of proteins. Histones can serve as the target substrate of PADI family isozymes, and therefore, the PADI family is involved in NETosis and the secretion of inflammatory cytokines. Thus, the PADI family is associated with the development of inflammatory autoimmune diseases and cancer, reproductive development, and other related diseases. In this review, we systematically discuss the role of the PADI family in the pathogenesis of various diseases based on studies from the past decade to provide a reference for future research.
Ankylosing spondylitis and glaucoma in European population: A Mendelian randomization study
Authors: Li Shengjie , Chen Minting , Zhang Qing , Fang Meijin , Xiong Wei , Bai Lang
Published: March 2023

Background

The relationship between ankylosing spondylitis (AS) and glaucoma in the European population remains unclear. In the present study, we applied a two-sample Mendelian randomization (MR) method to investigate their causal relationship.

Methods

MR analysis was conducted to validate the causal associations between AS with glaucoma using summary statistics from the genome-wide association studies of AS (9,069 cases and 13,578 control subjects) and glaucoma (8,591 cases and 210,201 control subjects). The inverse variance weighting method was performed to evaluate the causal relationship. The MR–Egger regression approach was applied to assess pleiotropy, while Cochran’s Q test was used to analyze heterogeneity. Subgroup analysis was performed according to primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG).

Results

The results of the MR study reveal a risk-increasing causal relationship between AS and glaucoma among European populations (OR = 1.35, 95%CI = 1.16–1.57, P = 8.81 × 10-5). Pleiotropy and heterogeneity were not found in our study. In the subgroup analysis, AS was also causal with POAG (OR = 1.48, 95%CI = 1.17–1.86, P = 8.80 × 10-4) and PACG (OR = 1.91, 95%CI = 1.03–3.51, P = 3.88 × 10-2).

Conclusion

The results of the MR analysis suggested a causal relationship between AS and glaucoma in the European population. Further studies are needed to identify the specific mechanism between these two diseases.
Case report: Sandwich therapy of CAR-T combined with ASCT: Sequential CAR-T cell therapy with ASCT after remission with CAR-T therapy caused long-term survival in a patient with relapsed/refractory Burkitt’s lymphoma with TP53 mutations
Authors: Zhang Qi , Zhu Xiaojian , Liu Bo , Zhang Yicheng , Xiao Yi
Published: March 2023

Burkitt’s lymphoma (BL) with TP53 mutation often has poor outcome after standard chemoimmunotherapy. Adoptive chimeric antigen receptor (CAR)-T cell therapy may be a new paradigm for treating refractory/relapsed (r/r) BL, but its therapeutic effects remain inconclusive. Here, we report a patient with r/r BL who failed to achieve complete remission (CR) and progressed rapidly after multiple protocol chemotherapy. The patient achieved CR with CAR19 and CAR22 T-cell cocktail therapy and obtained long-term disease-free survival after autologous hematopoietic stem cells (ASCT) and subsequential CAR19 and CAR22 T-cell cocktail therapy. The clinical evolution and genetic features of this case may provide some guidance for CAR-T therapy in overcoming relapses associated with TP53 gene mutations.
Effective differentiation of double negative thymocytes requires high fidelity replication of mitochondrial DNA in an age dependent manner
Authors: Limper Candice B. , Bondah Narda , Zhu Daphne , Villanueva Alanis N. , Chukwukere Uchenna K. , Huang Weishan , August Avery
Published: March 2023

One of the most proliferative periods for T cells occurs during their development in the thymus. Increased DNA replication can result in increased DNA mutations in the nuclear genome, but also in mitochondrial genomes. A high frequency of mitochondrial DNA mutations can lead to abnormal mitochondrial function and have negative implications on human health. Furthermore, aging is accompanied by an increase in such mutations through oxidative damage and replication errors. Increased mitochondrial DNA mutations cause loss of mitochondrial protein function, and decrease energy production, substrates, and metabolites. Here we have evaluated the effect of increased mitochondrial DNA mutations on T cell development in the thymus. Using mice carrying a mutant mitochondrial DNA polymerase γ (PolG) that causes increased mitochondrial DNA mutations, we show that high fidelity replication of mitochondrial DNA is pivotal for proper T cell development. Reducing the fidelity of mitochondrial DNA replication results in a premature age-dependent reduction in the total number of CD4/CD8 double negative and double positive thymocytes. Analysis of mitochondrial density in thymocyte subpopulations suggests that this may be due to reduced proliferation in specific double negative stages. Taken together, this work suggests that T cell development is regulated by the ability of mitochondria to faithfully replicate their DNA.
Case report: Preliminary response to tislelizumab plus S-1 in patients with metastatic gallbladder carcinoma: A report of five cases and a literature review
Authors: Zhang Yuzhu , Liu Yuchen , Liu Jing , Liu Tiande , Xiong Hu , Li Wen , Fu Xiaowei , Zhou Fan , Liao Shousheng , Fang Lu , Liang Bo
Published: March 2023

Gallbladder cancer (GBC) and cholangiocarcinoma are common cancers of the biliary system and are associated with a poor prognosis. Surgery and chemotherapy provide limited benefit to patients with advanced biliary tract carcinoma. Novel immunotherapies and molecularly targeted therapies are more effective options; however, few patients benefit and drug resistance is a concern. Here, we report five cases of advanced GBC with either high programmed death-ligand 1 (PD-L1) expression or a high tumor mutation burden (TMB-H). The patients were treated with a combination therapy of tislelizumab and S-1. The tumors were effectively controlled in most patients. One patient developed immune-related pneumonia (irP) during treatment, which resolved after hormone therapy, and the patient underwent surgery. Tislelizumab and S-1 were administered again after surgery; however, recurrent irP required discontinuation, and the tumor progressed after drug withdrawal. These cases demonstrate that combined therapy of anti-programmed cell death protein-1 (PD-1) antibodies and S-1 is a safe and effective regimen with few side effects for GBC patients, especially for sensitive populations (patients with TMB-H, microsatellite instability, deficient mismatch repair, or high expression of PD-L1). To our knowledge, this is the first time that tislelizumab in combination with S-1 has been used to treat patients with advanced GBC.
Hemorrhage complications in obstetric antiphospholipid syndrome: Risk factors and association with adverse pregnancy outcomes
Authors: Luo Yongjing , Jin Jiayang , Yan Yani , Zhang Mengyao , Hou Lei , Hou Yuke , Pei Qiuyan , Li Chun
Published: March 2023

Background

Bleeding complications are recognized as relatively infrequent manifestations of antiphospholipid syndrome (APS), and the safety of antithrombotic therapy during pregnancy is of concern. This study aims to assess the risk factors and possible associations between bleeding complications and adverse pregnancy outcomes (APOs) in patients with APS.

Methods

A retrospective cohort study was conducted at the Peking University People’s Hospital. The clinical and immunologic features, bleeding complications, treatment, and pregnancy outcomes of patients with APS were collected. Univariate and multivariate logistic regression analyses were applied to assess the associations between APOs and bleeding complications.

Results

A total of 176 participants with obstetric APS were included in the analysis. There were 66 (37.50%) patients with APS with hemorrhage complications and 86 (48.86%) patients with APS with APOs. Mucocutaneous hemorrhage was associated with APOs including fetal death after 12 weeks [odds ratio (OR) = 10.73, 95% confidence interval (CI): 1.61–71.74, p = 0.014], preterm delivery prior to 34 weeks (OR = 8.30, 95% CI: 2.31–29.84, p = 0.001), and small for gestational age (OR = 4.17, 95% CI: 1.22–14.21, p = 0.023) in univariate logistic regression analyses. It also independently associated with preterm delivery prior to 34 weeks (OR = 40.29, 95% CI: 1.45–1121.32, p = 0.030) in multivariate logistic regression analyses. Receiver operating characteristic (ROC) analysis evaluating the accuracy of these factors for preterm delivery prior to 34 weeks showed that the area under ROC curve was 0.871.

Conclusion

The study shows that mucocutaneous hemorrhage may be an indication of the occurrence of APOs in obstetric patients with APS.
Deficient leptin receptor signaling in T cells of human SLE
Authors: Liu Ting , Zheng Ming , Jia Li , Wang Mingyuan , Tang Longhai , Wen Zhenke , Zhang Miaojia , Yuan Fenghong
Published: March 2023

Background

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease mainly mediated by IgG autoantibody. While follicular helper T (Tfh) cells are crucial for supporting IgG autoantibody generation in human SLE, underlying mechanisms for Tfh cell mal-differentiation remain unclear.

Methods

In total, 129 SLE patients and 37 healthy donors were recruited for this study. Circulating leptin was determined by ELISA from patients with SLE and healthy individuals. CD4 T cells isolated from SLE patients and healthy donors were activated with anti-CD3/CD28 beads under cytokine-unbiased conditions in the presence or absence of recombinant leptin protein, followed by detection for Tfh cell differentiation by quantifying intracellular transcription factor Bcl-6 and cytokine IL-21. AMPK activation was assessed by analyzing phosphor-AMPK using phosflow cytometry and immunoblots. Leptin receptor expression was determined using flow cytometry and its overexpression was achieved by transfection with an expression vector. Humanized SLE chimeras were induced by injecting patients’ immune cells into immune-deficient NSG mice and used for translational studies.

Results

Circulating leptin was elevated in patients with SLE, inversely associated with disease activity. In healthy individuals, leptin efficiently inhibited Tfh cell differentiation through inducing AMPK activation. Meanwhile, leptin receptor deficiency was a feature of CD4 T cells in SLE patients, impairing the inhibitory effect of leptin on the differentiation of Tfh cells. As a result, we observed the coexistence of high circulating leptin and increased Tfh cell frequencies in SLE patients. Accordingly, overexpression of leptin receptor in SLE CD4 T cells abrogated Tfh cell mal-differentiation and IgG anti-dsDNA generation in humanized lupus chimeras.

Conclusion

Leptin receptor deficiency blocks the inhibitory effect of leptin on SLE Tfh cell differentiation, serving as a promising therapeutic target for lupus management.