bluuebunny/crossref_metadata_2025 huggingface dataset:
Eosinophilic Granulomatous Polyangitiis- a hopeful outcome of a Sinister disease- a case report
Authors: Debasish Roychoudhury  , Rammohan Gumpeni  , Kenneth Sha
Published: August 2024

Eosinophilic myocarditis is a rare form of myocardial inflammation characterized by eosinophilic infiltration and often accompanied by eosinophilia. It can be fatal in in its initial presentation. Although the condition is rare, it’s quite variable in terms of clinical presentation and prognosis ranging from fulminant myocarditis to uneventful recovery. We present a case of a young female patient with eosinophilic myocarditis who had favorable outcome after treatment with steroid and immunosuppressive agents.
Cardiovasc j 2024; 16(2): 102-104
Tectonic Geomorphology of Ultramafic Complex in Asera, North Konawe Regency
Authors: Faturrakhman Muhammad Luthfi , Dian Novita  , Akbar Cita  , Rohman  , Inge Triguri
Published: August 2024

Ultramafic complex in Sulawesi have many potential from mining to environmental aspects. The process of weathering and tectonic is a key factor in understanding how to utilize these potential. Tectonic geomorphology by using morphometric indices and field observation has proven to be a beneficial method in distinguishing the topography and morphogenetic development of a region due to the complex interaction between erosional processes and tectonic movements. IAT measurement of 71 sub-basins shows that tectonic activity in the research area are divided into 4 classes with values ranging from 1,5 – 2,6. Field observation shows that morphologically the research area are faulted hills consist of peridotite, dunite and pyroxenite with various degree of weathering. The effect of weathering also reveal on the shape of sub-basins and drainage density in the research area. Tectonic activity present in the form of intensive joint on some parts, with no clear correlation with IAT Class.
keyword: tectonic geomorphology, carbon capture storage, ultramafic, east Sulawesi ophiolite, morphometric indices
KAJIAN LITERATUR DESAIN UI/UX APLIKASI MOBILE UNTUK MANAJEMEN KONTROL KEHAMILAN
Authors: Sagala Muhammad Zikri Khatami , Andhika Giri Persada  , Aridhanyati Arifin
Published: August 2024

Perkembangan teknologi informasi dan komunikasi telah menghadirkan peluang besar dalam transformasi layanan kesehatan, termasuk manajemen kehamilan melalui aplikasi mobile. Desain UI (User Interface) dan UX (User Experience) menjadi krusial dalam memastikan efektivitas dan kepuasan pengguna dalam pengembangan aplikasi tersebut. Penelitian ini menggunakan pendekatan Design Thinking yang berorientasi pada pemahaman mendalam terhadap kebutuhan dan preferensi pengguna. Penelitian ini bertujuan untuk merancang dan mengembangkan aplikasi mobile yang dirancang khusus untuk manajemen kontrol kehamilan. Penelitian ini mengilustrasikan bagaimana pendekatan Design Thinking dapat diimplementasikan dalam pengembangan aplikasi kesehatan, dengan fokus pada penciptaan solusi yang efektif dan relevan bagi pengguna. Hasil dari penelitian ini diharapkan dapat memberikan kontribusi dalam peningkatan layanan kesehatan bagi ibu hamil melalui teknologi mobille.
DNA METİLASYONUNA NEDEN OLAN MİKOTOKSİNLERİN ELEKTROANALİTİK YÖNTEMLERLE ANALİZİ
Authors: Gürbüz Manolya Müjgan , Çoban Tülay , Doğan Topal Burcu
Published: August 2024

Amaç: DNA metilasyonunu etkileyen mikotoksinlerin analizi toksikolojide gıda güvenliği açısından oldukça önemlidir. Mikotoksin maruziyetinin kontrolü ile anlaşılması, gelişmiş gıda işleme teknikleri ve uygun depolama uygulamalarıyla birleştirildiğinde, gıda güvenliğinin artırılmasına olanak verir.
Sonuç ve Tartışma: Bu derleme, çeşitli yaygın mikotoksinlerin (aflatoksin B1, okratoksin A, vb.) neden olduğu DNA metilasyonundaki değişiklikleri ve bunların tespiti için kullanılan elektroanalitik yöntemleri özetlemektedir.
Oyster aquaculture enhances sediment microbial diversity: insights from a multi-omics study
Authors: Stevens JTE , Ray NE , Al-Haj AN , Fulweiler RW , Roy Chowdhury P
Published: August 2024

The global aquaculture industry has grown substantially, with consequences for coastal ecology and biogeochemistry. Oyster aquaculture can alter the availability of resources for microbes that live in sediments as oysters move large quantities of organic material to the sediments via filter-feeding, possibly leading to changes in the structure and function of sediment microbial communities. Further, oysters can initiate changes in sediment elemental concentrations, several of which are important mediators of microbial metabolism. Here, we use a chronosequence approach to investigate the impacts of oyster farming on sediment microbial communities over 7 yr of aquaculture activity in a temperate coastal system. We detected shifts in bacterial composition (16S rRNA gene amplicon sequencing), changes in gene expression (meta-transcriptomics), and variations in sediment elemental concentrations (sediment geochemistry) across different durations of oyster farming. Our results indicate that both the structure and function of bacterial communities vary between control (no oysters) and farm sites, with an overall increase in diversity and a shift towards anoxic tolerance in farm sites. However, little to no variation was observed in either structure or function with respect to farming duration, suggesting these sediment microbial communities are resilient to change. We also did not find any significant impact of farming on heavy metal accumulation in the sediments. The minimal influence of long-term oyster farming on sediment bacterial function and biogeochemical processes observed here provides important insights for establishing best practices for sustainable farming in these areas.
Nanobody-conjugated nanoparticles for photodynamic therapy
Authors:   , Maia Mesquita Bárbara Sofia
Published: August 2024

The aim of this work was to develop stable nanoparticles (NPs) for the systemic delivery of both hydrophobic and hydrophilic phthalocyanines that could improve specific accumulation of these photosensitizers (PS) in the tumor for targeted photodynamic therapy (PDT). Moreover, nanobodies with affinity to overexpressed membrane proteins were produced and conjugated to the surface of the NPs to facilitate their specific interaction with and internalization by cancer cells. The multivalency of these NPs in combination with a high number of target proteins on cancer cells theoretically increases their binding probability, which in turn augments the number of PS molecules that are internalized, and ultimately the extent of phototoxicity upon photodynamic therapy. This strategy intends to improve the PDT efficacy and advance its application as standard cancer treatment for cholangiocarcioma (CCA).In this thesis, different nanocarriers (e.g., liposomes and micelles) were employed in an attempt to improve the stability of different phthalocyanine-based photosensitizers (PSs) in the bloodstream and improve the accumulation of the PS in the tumor. The nanoparticles (NPs) with the highest retention of the PS when incubated with human plasma were selected using asymmetric flow-field flow fractionation, a technique that could be applied to test other active pharmaceutical ingredients and be an integrative part of the characterization of NPs in the pharmaceutical industry. We have also shown that nanobody (Nb)-targeted nanocarriers are very effective in vitro at increasing uptake and specific cell death in high membrane protein-expressing cancer cells, including cholangiocarcinoma (CCA) cells. The first in vivo studies performed with a CCA xenograft mouse model revealed an efficient accumulation of tetrasulphonated aluminium phthalocyanine in the tumor of mice injected with target and non-targeted liposomes. However, the Nb-targeted liposomes did not increase the overall PS association with cancer cells. While the initial hypothesis of this thesis was not confirmed in vivo, the PDT efficacy of PS-loaded nanocarriers remains to be compared with standard PDT regimens. Moreover, the data presented here raised relevant questions for future research in PDT.
AN ANALYSIS OF HOLDEN'S PSYCHOLOGICAL ANXIETY IN THE NOVEL "THE CATCHER IN THE RYE" BY J.D. SALINGER
Authors: Septyan Achmat Dony , Rosyadi Wildan Fakhri , Rohmana Wahyu Indah Mala
Published: August 2024

Our research aims to analyze the psychological problems experienced by Holden Caulfield, namely anxiety symptoms as the main character in the novel "The Catcher in The Rye" by studying his behavior and relationships or interactions with other characters in the novel. Holden has habits that are unusual for ordinary people and has poor interactions with other characters in the story, which makes his mental condition worse. We use qualitative research methods by collecting, analyzing, and describing primary data from the novel "The Catcher in The Rye" by J.D. Salinger in 1951. Then we also took other data from online sources. The results of this research shown that Holden has anxiety disorders which are indicated by mental and physical symptoms and also he has interactions with other characters that influence his anxiety. Suggestions that researchers can give for further research are to include solutions in solving social anxiety problems experienced by teenagers. This is because in this journal, the author does not include a solution to this problem.
THE TECHNIQUE AND TRANSLATION QUALITY OF FACE THREATENING ACTS (FTAS) IN ANNE OF GREEN GABLES
Authors: Poyungi Yurike Suhertian , Dessy Dwijayanti
Published: August 2024

Abstract
This study is a descriptive qualitative that aims to describe the types of Face threatening Acts (FTAs). Besides, this study also aims to analyze the translation techniques and the translation quality of a novel entitles Anne of Green Gables. It is found that 37 utterances which accommodates FTAs in the orientation structure of the novel and involves 4 types of FTAs, they are bald on record (18 data), off record (6 data), FTA using positive politeness (3 data), and FTA using negative politeness (10 data). The translation techniques used to translate the FTAs are established equivalence, linguistic amplification, discursive creation, addition, borrowing, reduction, and modulation. Established equivalence is the most dominant techniques. Therefore, the translation quality of FTAs in Anne of Green Gables is accurate, acceptable, and readable.
MANIFESTASI LAKU DALAM KAWRUH: TINJAUAN DESKRIPTIF PADA CERPEN “MEGURU” KARYA SENGKUNI
Authors: Teguh Prasetyo
Published: August 2024

Abstrak
Dalam budaya Jawa, dikenal berbagai macam konsep-konsep religi. Konsep-konsep tersebut mengarah kepada perilaku mistik. Perilaku-perilaku tersebut biasanya terwujud dalam laku. Laku, dalam konteks budaya Jawa atau manusia Indonesia, merupakan sebuah upaya mencapai suatu tujuan yaitu kesempurnaan. Kawruh merupakan salah satu bentuk perilaku mencari tahu dengan berguru pada orang lain atau buku. Dalam kawruh sebagai sebuah kegiatan mencari tahu/berguru, terdapat bentuk-bentuk tindakan yang dapat dikategorikan sebagai laku. Cerpen berjudul “Meguru” karya Sengkuni memperlihatkan kelindan laku dan kawruh di dalam gambaran kehidupan masyarakat Jawa tradisional. Artikel ini akan membedah bentuk-bentuk laku yang merupakan manifestasi dari kawruh yang termuat dalam cerpen “Meguru” karya Sengkuni tersebut. Artikel ini menggunakan metode kualitatif dan teknik pembacaan dekat. Untuk menelaah lebih jauh kelindan laku dan kawruh tersebut akan dirujuk konsep-konsep religi Jawa yang relevan. Dari pembacaan dekat ini, ditemukan bahwa laku-laku dalam cerpen “Meguru” ini diwujudkan dalam bentuk-bentuk seperti lelana brata, ritual dialog dengan guru, dan tindakan-tindakan asketis yang menjadi ciri keseharian tokoh yang merepresentasikan filosofi masyarakat Jawa tradisional.
 
Kata kunci: kawruh, laku, kanoman, kasepuhan.
 
 
Abstract
In Javanese culture, there are various religious concepts. These concepts lead to mystical behaviors. These behaviors are usually manifested in practices. Laku, in the context of Javanese culture or Indonesian humans, is an effort to achieve a goal of perfection. Kawruh is a form of behavior to find out by studying with other people or books. In kawruh as an activity of finding out/teaching, there are forms of action that can be categorized as practice. The short story "Meguru" by Sengkuni shows the intertwining of laku and kawruh in the life of traditional Javanese society. This article will dissect the forms of laku that are manifestations of kawruh contained in the short story "Meguru" by Sengkuni. This article uses qualitative methods and close reading techniques. To further examine the intertwining of laku and kawruh, relevant Javanese religious concepts will be referred to. From this close reading, it is found that the practices in the short story "Meguru" are manifested in forms such as lelana brata, ritual dialogue with the teacher, and ascetic actions that characterize the daily life of the characters who represent the philosophy of traditional Javanese society.
 
Keywords: kawruh, laku, kanoman, kasepuhan.
Differential diagnosis of cataplexy and generalized epilepsy. Case report
Authors: Lebedeva A. V. , Pantina N. V. , Efimenko A. P. , Volokitin V. V. , Bokitko T. A. , Kovaleva I. I. , Beskhlebnaia M. A. , Tolmacheva A. I. , Stoyakina V. V.
Published: August 2024

Cataplexy is rare disease, the main clinical features of which are loss of muscle tone without loss of consciousness, associated with specific factors such as laughter, and less often fear, anger or crying. The differential diagnosis of epileptic seizures and cataplexy is often difficult because of similar clinical features. Establishing the diagnosis of cataplexy is important because in most cases it is associated with narcolepsy; in addition, misinterpretation of cataplexy can lead to hyperdiagnosis of epilepsy or wrong efficiency mark of antiepileptic drugs. Clinical and instrumental examination is necessary to establish the right diagnosis. Literature review and own clinical case is described.
Suicidal behavior with diseases of the endocrine system, eating disorders and metabolic disorders
Authors: Bisaliev R. V.
Published: August 2024

The purpose of the work is to study: analyze modern data on the problem of suicidal behavior in the structure of diseases of the endocrine system, eating disorders and metabolic disorders. Materials and methods. The analysis of 52 sources. The search was carried out in special medical resources, namely: RusMed, Medline, PubMed, and Web of Science. In addition, electronic libraries such as eLibrary were involved.RU, CyberLeninka and the Library of dissertations and abstracts of Russia dslib.net. Results. An attempt has been made to study the phenomenon of suicidal behavior in the structure of diseases of the endocrine system, eating disorders and metabolic disorders. In addition to studying the prevalence of suicidal behaviors in the above diseases, the features and clinic of suicidal behavior depending on the duration and stage of somatic diseases were also described. The risk of suicidal behavior is higher than in the general population at all stages of the development of somatic disease and treatment, including remission, is underestimated by statistics. Conclusions. Diseases of the endocrine system, eating disorders and metabolic disorders should be considered by specialists as potentially dangerous conditions. Suicidal activity in the structure of these diseases remains very high and varies widely: from 0.10 to 65 %. The greatest suicidal activity is manifested in patients with the following diseases: diabetes mellitus, Hashimoto's thyroiditis, hypothyroidism, hyperthyroidism, obesity; Preventive strategies are proposed, which show the importance of screening suicidal behavior in the general medical network in view of the high incidence of suicides to specialists.
Pattern of cognitive changes and content of cerebral neurotrophic factor in patients with chronic cerebral ischemia
Authors: Slyusar T. A. , Slyusar I. N. , Vasilyeva I. V.
Published: August 2024

Objective. To study the pattern of cognitive changes and the content of cerebral neurotrophic factor (BDNF) in the blood serum of patients with chronic cerebral ischemia (CICI).Materials and methods. We examined 128 people who were divided into two groups: the main group – 82 patients (38 men and 44 women) aged 60–74 years with CICI, the control group – 46 people comparable to the patients of the main group by gender and age, but without clinical manifestations of CICM. Cognitive functions were assessed using the Mini-Mental Status Scale (MSMS) and the Battery of Tests for the Assessment of Frontal Dysfunction (FMS). Attention (Schulte test), speech fluency (speech fluency subtest BTLD, verbal association test), memory (memory subtest KSHOPS; 5 words test) and visuospatial functions (clock drawing test) were studied. The content of BDNF in the blood serum of patients was determined by the enzyme immunoassay method.Results. The pattern of cognitive impairment in CIGM was characterized by changes in the domains of executive brain functions and complex attention. The content of BDNF in the blood serum of patients with CICI was significantly lower than that of the control group; in men is lower compared to female patients. Significant correlations were revealed between the severity of cognitive disorders and the level of BDNF in the blood serum.
Post-stroke pain syndrome: clinical, pathophysiological characteristics and modern rehabilitation management
Authors: Petrova L. V. , Kostenko E. V. , Nakhrapov D. I. , Zhdanova S. G.
Published: August 2024

Background. Pain is a common complication after stroke and is associated with the presence of depression, cognitive dysfunction, and impaired quality of life. It remains underdiagnosed and undertreated, despite evidence that effective treatment of pain may improve function and quality of life. The article highlights the issues of epidemiology, pathogenesis, methods of clinical assessment and risk factors for the development of post-stroke pain. A review of the literature on the most common post-stroke pain syndromes including central post-stroke pain, complex regional pain syndrome, musculoskeletal pain, shoulder pain, pain associated with spasticity and headache is presented. Modern management of the pain is analyzed.Conclusion. In the best interests of optimizing the rehabilitation of a stroke patient, improving his quality of life and function after stroke, clinicians should be aware of pain as a common complication after stroke, identify those patients at highest risk, detail the presence and characteristics of pain, and also be aware of options for correcting post-stroke pain syndromes.
Papillary fibroelastoma of the aortic valve as a cause of acute coronary syndrome
Authors: Pletnev N. E. , Antonov I. M. , Libov I. A. , Komarova A. G. , Rodionov E. P. , Alekseev V. G.
Published: August 2024

Papillary fibroelastomas represent the second most common group of heart tumors, second only to myxoma. In most patients, the disease is asymptomatic, however, in the case of clinical manifestations, the most common are: embolic syndrome with the development of acute cerebrovascular accident, myocardial infarction. Papillary fibroelastoma is a benign tumor growing from endocardial cells, affecting mainly cardiac valves. To date, echocardiography performed by transthoracic and transesophageal access remains the most accessible method for tumor imaging. The main method of treatment of papillary fibroelastoma is surgery. The prognosis is usually favorable. We present a clinical case of papillary fibroelastoma in a 58-year-old man complicated by type 2 myocardial infarction.
KONSEP RUANG DAN JALUR WISATA EDUKASI (EDUFARM) DEWI SRI DI DESA SITUSARI KECAMATAN CILEUNGSI, KABUPATEN BOGOR
Authors: Febriani Yusi
Published: August 2024

ABSTRAK Desa Situsari merupakan salah satu desa yang ada di Kecamatan Cileungsi, Kabupaten Bogor, Provinsi Jawa Barat. Desa Situsari memiliki sejumlah potensi untuk dikembangkan menjadi Desa Wisata. Namun dalam upaya ini perlu adanya perencanaan matang terkait pemanfaatan potensi wisata yang ada di desa dan  dimulai dari konsep rencana ruang dan jalur wisata, yang nantinya akan dijadikan panduan pengembangan desa wisata. Tujuan dari penelitian adalah merencanakan konsep desa wisata berdasarkan potensi yang ada di desa tersebut. Metode yang digunakan adalah metode perencanaan tapak teridiri dari dari tahap survei, identifikasi dan konsep perencanaan wisata.  Pada penelitian ini  dibatasi sampai tahap konsep perencanaan. Konsep desa wisata yang direncanakan adalah konsep ramah lingkungan berbasis partisipasi masyarakat yang mencirikan budaya atau kebiasaan dari penduduk setempat.  Konsep wisata yang memungkinkan bisa dikembangkan di Desa Situsari berdasarkan potensi wisata setempat adalah konsep wisata edukasi dibidang pertanian (edufarm). Konsep wisata edukasi yang direncanakan di sesuaikan dengan masing-masing potensi sumberdaya alam dan sumber daya masyarakat.  Penelitian ini menghasilkan konsep wisata budi daya anggur pada KRL Anggur, budidaya dari berbagai produk hortikultur di KRL harmoni dan budidaya padi di sekitar danau Daham Ilnuris. Kata Kunci : Desa Situsari, Desa Wisata, wisata edukasi pertanian ABSTRACT Situsari Village is one of the villages in Cileungsi district, Bogor regency, West Java Province.  Situsari Village has a number of potentials to be developed into a tourist village.  However, in this effort there needs to planning regarding the utilization of tourism potential in the village and starting form the concept of spatial planning and tourist routes, which will later be used as a guide for developing tourist village. The aim of the research is to plan a tourism village concept based on the potential that exists in the village.  The method used is the site planning consisting of the survey, identification and tourism planning concept.  This research is limited to the concept planning. The planned tourist village concept is an environmentally friendly concept based on community participation that characterizes the culture or habits of the local population.  A tourism concept that could possibly be developed in Siteari Village based on local tourism potential is the concept of educational tourism in the agricultural sector (edufarm). The planned educational tourism concept is adjusted to each potential natural resource and community resource.  This research resulted in the concept of wine cultivation tourism on the  KRL Anggur, cultivation of various horticultural products on the  KRL Hramoni Berseri and rice cultivation around the Daham Ilnuris lake. Keywords: Situsari Village, Tourism Village, Edufarm tourism
Metabolic dysfunction in youth with major mood disorders: Implications for prevention and early intervention.
Authors: McKenna Sarah , Carpenter Jo , Shin Mirim , Park Shin , Crouse Jacob J , Scott Elizabeth M , Hickie Ian B
Published: August 2024

Early intervention for premature cardiovascular disease is critical for reducing the increased mortality rates associated with major mood and affective disorders. Alongside smoking, a greater emphasis has now been placed on metabolic dysfunction as a causal pathway, with higher body mass index being proposed as a key modifiable risk factor. Accordingly, early intervention frameworks currently promote nutritional counselling, lifestyle interventions, and medication switching to address early metabolic risk factors in youth with major mood disorders. Yet there is currently limited evidence that such approaches benefit metabolic outcomes in this population, even when they lead to weight loss. The current paper is a narrative review based on searches of Google Scholar, PubMed and Scopus. It will summarise four key areas of research: (1) Evidence that young people presenting to early interventions services show higher rates of metabolic dysfunction to the general population, particularly insulin resistance, despite normal rates of being overweight and normal blood glucose; (2) Evidence that complex pathophysiological mechanisms other than weight gain link mood disorders and metabolic dysfunction; (3) Evidence regarding traditional lifestyle interventions on metabolic outcomes for individuals with mood disorders; and (4) Alternative intervention approaches (such as metformin and circadian therapies) showing promising results for improved metabolic outcomes. This evidence has important implications for monitoring and early treatment of metabolic dysfunction in young people with major mood disorders.
Efficient biosynthesis of D/L-alanine in the recombinant Escherichia coli BL21(DE3) by biobrick approach
Authors: Naeem Muhammad , Hao Shimiao , Chu Mengqiu , Zhang Xuan , Huang Xinyan , Wang Jiaying , He Guangzheng , Zhao Baohua , Ju Jiansong
Published: August 2024

Alanine is the most abundant chiral amino acid that exists into the D-alanine or L-alanine forms with diverse applications in the biomedical, pharmaceutical, plastics, and food industries. D/L-alanine production can be carried out through chemical, microbial fermentation, and biocatalytic methods and not much effective due to complicated processes or purification issues and is still challenging to achieve a higher yield. In the present study, biobrick method was utilized for efficient production of D/L-alanine in the recombinant Escherichia coli BL21(DE3) with tandem three-gene co-expression plasmid. Firstly, the co-expression plasmid pET-22bNS-DadX-Ald-Gdh containing three genes, alanine dehydrogenase (ald), alanine racemase (dadX), and glucose dehydrogenase (gdh) from Bacillus pseudofirmus OF4 were successfully constructed and introduced into the E. coli BL21(DE3) strain. Then, under optimized conditions in the whole-cell biocatalytic reaction [20 mM Na2CO3-NaHCO3 (pH 10.1), 200 mM D-glucose, 200 mM sodium pyruvate, and 200 mM ammonium chloride], the concentration of D-alanine and L-alanine reached the maximum value (6.48 g/L and 7.05 g/L) after 3.0 h reaction time at 37°C under 180 rpm rotation. Meanwhile, promoter replacement experiments and Western blot analysis revealed that the expression level of protein OF4Ald had a significant effect on the production of D/L-alanine, indicating that alanine dehydrogenase might be the rate-limiting enzyme for D/L-alanine synthesis. This study provides a simple, feasible, and efficient biosynthesis process of D/L-alanine, which could explore emerging applications for large-scale production of industrial bioproducts.
Computational insights into rational design and virtual screening of pyrazolopyrimidine derivatives targeting Janus kinase 3 (JAK3)
Authors: Faris Abdelmoujoud , Cacciatore Ivana , Alnajjar Radwan , Aouidate Adnane , AL Mughram Mohammed H. , Elhallaoui Menana
Published: August 2024

The Janus kinase 3 (JAK3) family, particularly JAK3, is pivotal in initiating autoimmune diseases such as rheumatoid arthritis. Recent advancements have focused on developing antirheumatic drugs targeting JAK3, leading to the discovery of novel pyrazolopyrimidine-based compounds as potential inhibitors. This research employed covalent docking, ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) analysis, molecular dynamics modeling, and MM/GBSA (Molecular Mechanics Generalized Born Surface Area) binding free energy techniques to screen 41 in silico-designed pyrazolopyrimidine derivatives. Initially, 3D structures of the JAK3 enzyme were generated using SWISS-MODEL, followed by virtual screening and covalent docking via AutoDock4 (AD4). The selection process involved the AMES test, binding affinity assessment, and ADMET analysis, narrowing down the candidates to 27 compounds that passed the toxicity test. Further covalent docking identified compounds 21 and 41 as the most promising due to their high affinity and favourable ADMET profiles. Subsequent development led to the creation of nine potent molecules, with derivatives 43 and 46 showing exceptional affinity upon evaluation through molecular dynamics simulation and MM/GBSA calculations over 300 nanoseconds, comparable to tofacitinib, an approved RA drug. However, compounds L21 and L46 demonstrated stable performance, suggesting their effectiveness in treating rheumatoid arthritis and other autoimmune conditions associated with JAK3 inhibition.
Microscopic distribution of taxanes in freeze-fixed stems of Taxus cuspidata
Authors: Gong Qinyue , Aoki Dan , Yoshida Masato , Fukushima Kazuhiko
Published: August 2024

Introduction

Taxus species contain the anticancer alkaloid paclitaxel, as well as other taxanes similar in structure and potentially in effect to paclitaxel. Tissue-specific distribution patterns and seasonal variations of taxanes in some Taxus species have been reported; however, it is still under-presented for the taxanes in Taxus cuspidata.

Methods

The radial distributions of eight taxanes in the transverse surface of freeze-fixed T. cuspidata stems from the late summer and the spring seasons were investigated by cryo-time-of-flight secondary ion mass spectrometry and scanning electron microscopy (cryo-TOF-SIMS/SEM) visualization and liquid chromatography-mass spectrometry (LC-MS) quantitative analysis. By optical microscopic observation, seasonal differences in the amounts and distribution patterns of target taxanes were further characterized in specific tissues.

Results and Discussion

The overall amount of taxanes was higher in the late summer than in the spring. Also, taxanes’ radial distribution was generally found at higher concentration in the phloem, the cambium and lower level in the periderm, the latest-forming xylem, with different taxanes showing several patterns with distinction between seasons, which were considered related to seasonal plant physiological behaviors. In addition, the distribution of baccatin III (BAC) was investigated at the cellular level, which was regarded in specific cells suggesting its transport in the radial and axial directions in the T. cuspidata stem. Characterizing the microscopic distribution of taxanes in the T. cuspidata stem is expected to play a role in the further study of their biosynthesis and in planta behaviors.
Exploring the gut microbiota’s effect on temporomandibular joint disorder: a two−sample Mendelian randomization analysis
Authors: Zhao Kai , JI Shuaiqi , Jiang Han , Qian Yunzhu , Zhang Weibing
Published: August 2024

Background

Temporomandibular joint disorders (TMD) are highly prevalent among people. Numerous investigations have revealed the impact of gut microbiota in many diseases. However, the causal relationship between Temporomandibular joint disorders and gut microbiota remains unclear.

Methods

Genome-Wide Association Studies (GWAS) refer to the identification of sequence variations, namely single nucleotide polymorphisms (SNPs), existing across the entire human genome. GWAS data were collected on gut microbiota and TMD. Then, instrumental variables were screened through F-values and removal of linkage disequilibrium. These SNPs underwent mendelian analysis using five mathematical models. Sensitivity analysis was conducted to further verify the stability of the results. Pathogenic factors of TMD mediate the causal relationship between gut microbiota and TMD were explored through a two-step Mendelian randomization analysis. Finally, reverse mendelian analysis was conducted to account for potential reverse effects.

Results

The analysis of the data in this article suggests that some gut microbiota, including Coprobacter, Ruminococcus torques group, Catenibacterium, Lachnospiraceae, Turicibacter, Victivallis, MollicutesRF9, Methanobacteriales, Methanobacteriaceae, FamilyXI, Methanobacteria were identified as risk factors, while Peptococcaceae provides protection for TMD.

Conclusion

The research reveals the relation of gut microbiota in TMD. These findings provide insights into the underlying mechanisms and suggest potential therapeutic strategy.
Reference management in written narrative production by Spanish-Italian bilingual children
Authors: Leonetti Escandell Victoria
Published: August 2024

This paper is an investigation of reference production in 84 Italian-Spanish bilingual children aged 8 to 12. The study explores whether such reference production is influenced by either the type of referential expression involved or language dominance by analyzing how these children manage reference. The children’s relative proficiency in the two languages (and thus their language dominance) was assessed through a cloze-test, and their narrative production was evaluated using a retelling task. Results indicated a preference for null pronouns to refer to subjects and full referential expressions for objects, with Italian showing a higher occurrence of full referential expressions. Dominance in either language did not significantly impact reference production. This suggests that bilingual children can distinguish between language-specific patterns, a behavior consistent with adult monolingual groups. These results contribute to our understanding of bilingual reference management and shed light on the role played by language and language dominance.
Density structures of the upper mantle in the East African Rift System: implications for the evolution of intracontinental rifting
Authors: Tao Wenfeng , Liang Qing , Chen Chao
Published: August 2024

The East African Rift System (EARS) provides an ideal natural laboratory for studying the mechanisms of tectonic plate breakup and continental drift, as well as a unique perspective for exploring the maturation process of continental rifting and its drivers. This study combines high-resolution satellite gravity data and seismic tomography model with an integrated geophysical approach to reveal the density structures in the upper mantle of the EARS. The results show that the northeastern to central Congo and Zimbabwe Craton exhibit significant high-density anomalies extending up to 250 km, which is indicative of a thicker and more intact lithosphere. In contrast, the Uganda, Tanzania, eastern and southern Congo, and Kaapvaal Craton show shallow high-density anomalies underlain by low-density anomalies that are clearly derived from the deeper mantle, indicating a thining of the lithosphere with some degree of possible melting at the base. The various rift segments of the EARS exhibit different rift morphologies. The Main Ethiopian Rift and the Kenya Rift of the Eastern Rift Branch show strong low-density anomalies, indicating intense melting, which is much stronger than that observed in the Western Rift Branch. However, the two rifts may have originated from the same mantle uplift in which the low-density anomalies of the Eastern and Western Rift Branches connected in the deep upper mantle. The lower portion of the Malawi Rift exhibits weaker low-denstiy anomalies, which can be observed to the south of the Malawi Rift, extending further south as a continuation of the EARS. Combining the results of previous kinetics simulations and our density perturbation results, it can be inferred that the Eastern Rift Branch is mainly affected by active rifting, while the Western Rift Branch is affected by both active and passive rifting.
Trait emotional intelligence and foreign language performance: associations with academic self-efficacy and foreign language anxiety
Authors: Jin Feiyang , Gu Chufeng , Li Yu
Published: August 2024

Recent years have witnessed extensive research examining the influences of positive psychological factors in foreign language learning. Building on these endeavors, the current study was specifically designed to examine how positive psychological factors including trait emotional intelligence (TEI), academic self-efficacy, and foreign language anxiety (FLA) exert influences on foreign language performance in college students who are learning a foreign language. To this end, 203 Chinese college students (141 women), recruited through snowball sampling, completed three validated questionnaires to measure their TEI (Trait Emotional Intelligence Questionnaire - Short Form), academic self-efficacy (the Chinese version of the Academic Self-Efficacy Questionnaire), and FLA levels (the Chinese version of Foreign Language Classroom Anxiety Scale). Additionally, an in-house self-rating questionnaire assessed their self-perceived foreign language performance. Mediation analysis was used to determine whether and how academic self-efficacy and FLA levels contribute separately and interactively to the relationship between TEI and foreign language performance. The results showed that: (a) there were moderate to strong associations between TEI, academic self-efficacy, FLA levels, and self-perceived foreign language performance; and (b) academic self-efficacy and FLA levels played separate and sequential mediating roles between TEI and self-perceived foreign language performance. Together, these findings highlight how TEI, academic self-efficacy, and FLA levels contribute to foreign language performance in college students. They also suggest the potential application of these positive psychological factors in mitigating anxiety elicited by learning a foreign language and improving language performance.
University experiences of students and graduates with neurodiversity: tools for creating a specialized mentoring program related to working life
Authors: Aguilera Rodríguez Gerardo , Márquez González Claudia Verónica , Villaseñor-Cabrera Teresita J. , Valadez Sierra María de los Dolores
Published: August 2024

Introduction

The term neurodiversity encompasses a range of conditions, including autism, attention deficit and hyperactivity disorder, dyslexia, and dyscalculia. In higher education, students with these conditions often face barriers that hinder their optimal academic performance. These barriers stem from their specific needs and institutional requirements. This situation can also negatively impact their ability to transition into the workforce. Therefore, it is necessary to design strategies that ensure specialized support for this population, guided by the opinions of neurodiverse students. The objective of this study is to identify the needs, difficulties, and tools related to the transition into the workforce, as reported by neurodiverse students and graduates from the bachelor's degree in psychology program, who present some conditions of neurodiversity.

Methods

For this purpose, a qualitative/phenomenological research was carried out.

Results

The gathered opinions revealed that the main needs of students include the following: increased awareness and capacity within higher education institutions for timely diagnosis, the implementation of reasonable adjustments for better integration into their activities, provision of supportive environments, the development of strategies to enhance cognitive and emotional aspects, such as planning skills, time management, and emotional regulation skills.

Discussion

The results of this study are consistent with other studies that emphasize the importance of creating a compassionate pedagogy in educational settings. This involves a greater commitment from educators to address and improve pedagogical practices, provide necessary tools, and develop strategies to help students with neurodiversity conditions throughout their careers. The limitations of this study include the small sample size and restricted depth of the interviews. Therefore, future research should increase the number of participants and explore the interviews in greater depth.
Lack of membrane sex steroid receptors for mediating rapid endocrine responses in molluscan nervous systems
Authors: Fodor István , Matsubara Shin , Osugi Tomohiro , Shiraishi Akira , Kawada Tsuyoshi , Satake Honoo , Pirger Zsolt
Published: August 2024

Despite the lack of endogenous synthesis and relevant nuclear receptors, several papers have been published over the decades claiming that the physiology of mollusks is affected by natural and synthetic sex steroids. With scant evidence for the existence of functional steroid nuclear receptors in mollusks, some scientists have speculated that the effects of steroids might be mediated via membrane receptors (i.e. via non-genomic/non-classical actions) - a mechanism that has been well-characterized in vertebrates. However, no study has yet investigated the ligand-binding ability of such receptor candidates in mollusks. The aim of the present study was to further trace the evolution of the endocrine system by investigating the presence of functional membrane sex steroid receptors in a mollusk, the great pond snail (Lymnaea stagnalis). We detected sequences homologous to the known vertebrate membrane sex steroid receptors in the Lymnaea transcriptome and genome data: G protein-coupled estrogen receptor-1 (GPER1); membrane progestin receptors (mPRs); G protein-coupled receptor family C group 6 member A (GPRC6A); and Zrt- and Irt-like protein 9 (ZIP9). Sequence analyses, including conserved domain analysis, phylogenetics, and transmembrane domain prediction, indicated that the mPR and ZIP9 candidates appeared to be homologs, while the GPER1 and GPRC6A candidates seemed to be non-orthologous receptors. All candidates transiently transfected into HEK293MSR cells were found to be localized at the plasma membrane, confirming that they function as membrane receptors. However, the signaling assays revealed that none of the candidates interacted with the main vertebrate steroid ligands. Our findings strongly suggest that functional membrane sex steroid receptors which would be homologous to the vertebrate ones are not present in Lymnaea. Although further experiments are required on other molluscan model species as well, we propose that both classical and non-classical sex steroid signaling for endocrine responses are specific to chordates, confirming that molluscan and vertebrate endocrine systems are fundamentally different.
Case report: A novel mutation of the CAPN3 gene in a Chinese family with limb-girdle muscular dystrophy type 2A
Authors: Feng Wanjun , Cao Yanyan , Ren Ruolin , Yang Xiaohui , Cao Chunyan , Jiang Hongwei , Du Ganqin
Published: August 2024

Limb-girdle muscular dystrophy type 2A (LGMD R1 Calpain 3-Related, LGMD2A/R1), an autosomal recessive disorder, is characterized by progressive muscle weakness with a prominent presentation in the proximal limb girdle muscles. LGMD2A/R1, which is caused by variants in calcium-activated neutral proteinase 3 (CAPN3), is the most common. The present study aimed at identifying the clinically significant variants in a Chinese family with LGMD2A/R1 and exploring the genotype–phenotype correlations. Clinical symptoms, laboratory findings, and physical examinations were obtained. Genomic DNA was extracted from the peripheral blood samples of this family. Whole-exome sequencing (WES) and Sanger sequencing were used to explore and validate the pathogenic genes. In this study, the proband and his sister, who had two identical mutations in the CAPN3 gene sequence, exhibited diverse clinical features, including disease onset and progression. The mutation c.2120 A>G (p. D707G) is pathogenic and has been reported in the Human Gene Mutation Database (HGMD) and the ClinVar database. c.1783-72 C>G may be a novel pathogenic mutation of LGMD2A/R1 based on the American College of Medical Genetics (ACMG) guidelines, which widens the gene variant pool in CAPN3 and improves diagnosis and genetic counseling.
Contemporary review of IgA nephropathy
Authors: Filippone Edward J. , Gulati Rakesh , Farber John L.
Published: August 2024

IgA nephropathy (IgAN) is considered the most common primary glomerulonephritis worldwide with a predilection for Asian-Pacific populations and relative rarity in those of African descent. Perhaps 20%–50% of patients progress to kidney failure. The pathogenesis is incompletely understood. Mesangial deposition of immune complexes containing galactose-deficient IgA1 complexed with anti-glycan IgG or IgA antibodies results in mesangial cell activation and proliferation, inflammatory cell recruitment, complement activation, and podocyte damage. Diagnosis requires a biopsy interpreted by the Oxford criteria. Additional pathologic features include podocytopathy, thrombotic microangiopathy, and C4d staining. Biomarkers predicting adverse outcomes include proteinuria, reduced GFR, hypertension, and pathology. Acceptable surrogate endpoints for therapeutic trials include ongoing proteinuria and rate of eGFR decline. The significance of persisting hematuria remains uncertain. The mainstay of therapy is supportive, consisting of lifestyle modifications, renin–angiotensin inhibition (if hypertensive or proteinuric), sodium-glucose-transporter 2 inhibition (if GFR reduced or proteinuric), and endothelin-receptor antagonism (if proteinuric). Immunosuppression should be considered for those at high risk after maximal supportive care. Corticosteroids are controversial with the most positive results observed in Chinese. They carry a high risk of serious side effects. Similarly, mycophenolate may be most effective in Chinese. Other immunosuppressants are of uncertain benefit. Tonsillectomy appears efficacious in Japanese. Active areas of investigation include B-cell inhibition with agents targeting the survival factors BAFF and APRIL and complement inhibition with agents targeting the alternate pathway (Factors B and D), the lectin pathway (MASP-2), and the common pathway (C3 and C5). Hopefully soon, the who and the how of immunosuppression will be clarified, and kidney failure can be forestalled.
Defining fatigue from the experiences of patients living with chronic fatigue
Authors: Rio Carielle Joy , Gehling Gina M. , Blumhorst Catherine , Ross Alexander , Saligan Leorey N.
Published: August 2024

Introduction

Fatigue is a multidimensional, highly individualized symptom experience perceived by people, regardless of health status. It is the most common complaint among those seeking primary care, yet, despite being a frequently reported symptom, it remains poorly understood.

Methods

This is an exploratory study utilizing a qualitative descriptive approach that aims to explore the description of fatigue from the personal experiences of 16 participants living with chronic fatigue. Themes were generated from transcripts of in-depth interviews that focused on a central question: “how would you describe your fatigue from your own experience?”

Results

Analysis of the participants’ interview transcripts revealed three themes. The first theme focused on fatigue as a unique personal experience, which included experiential descriptions or measures of fatigue that the participants used to describe their symptoms. The second theme focused on fatigue as an experience beyond self, which highlighted the consequences of fatigue on interpersonal interactions and the performance of social roles, as well as the potential of utilizing social support to cope with the limitations caused by this condition. The last theme was on living with fatigue, which focused on ways participants attempted to discern their condition and manage the consequences of fatigue.

Discussion

Experiences of chronic fatigue have patterns and personal meanings that vary between individuals. Caring for persons experiencing chronic fatigue requires acknowledgment of unique personal experiences and coping strategies. Due to the nature of the method, the results of this study are not generalizable and only reflect the experiences of the participants.