bluuebunny/crossref_metadata_2025 huggingface dataset:
Pengaruh Desain Interior pada Kinerja Logistik di Pusat Distribusi E-commerce di Surabaya - Sidoarjo
Authors: Rachmanto Danny Dwi , Ardianto Rizal , Fatimah Siti , Puspita Feni Ira
Published: November 2024

Penelitian ini mengevaluasi pengaruh desain interior terhadap kinerja logistik di pusat distribusi e-commerce melalui metode eksperimen dan analisis data operasional. Eksperimen melibatkan penerapan variasi desain interior di pusat distribusi e-commerce, dengan variabel kontrol dan dependen yang telah ditentukan. Data kinerja logistik dikumpulkan melalui observasi, sensor, dan sistem manajemen gudang. Analisis data mencakup uji statistik (ANOVA, regresi), perhitungan KPI, visualisasi data, serta analisis korelasi dan tren. Hasil penelitian menunjukkan bahwa desain interior yang optimal dapat meningkatkan kecepatan pengambilan dan pengemasan barang, efisiensi ruang, serta kepuasan pekerja. Implikasi penelitian ini menegaskan pentingnya investasi dalam desain interior yang mengacu pada alokasi sumber daya (seperti waktu, uang, dan tenaga) untuk merancang, mengimplementasikan, dan mengoptimalkan tata letak dan lingkungan kerja untuk meningkatkan kinerja logistik dan kepuasan pelanggan. Direkomendasikan agar perusahaan e-commerce meningkatkan kerjasama antara tim desain dan operasional, melibatkan pekerja dalam perancangan, serta melakukan evaluasi berkala terhadap desain interior untuk memaksimalkan efisiensi operasional dan daya saing.
Factors Related to The Activity Of Posyandu Cadres in The Immunization Program of Sudirejo Village I
Authors: Siagian Laili , Hasibuan Rapotan
Published: November 2024

In posyandu, the role of cadres is to be able to show their figure and be active in one of the health programs, namely immunization. Posyandu Sudirejo I village is under the coordination of puskesmas Simpang Limun with 11 (42.31%) active posyandu. This study aims to determine the factors associated with the activeness of posyandu cadres in the immunization program in Sudirejo I village, Medan City. The method in the study used quantitative methods with a cross sectional research design. A total of 55 cadres were used as samples using univariate and bivariate analysis using the chi-square test (p<α0.05). The results showed that active respondents were 29 (52.7%), while inactive respondents were 26 (47.3%). There are results of several research variables, namely knowledge (p 0.002 <α 0.05), motivation (p 0.002 <α 0.05), infrastructure (p 0.022 <α 0.05), interpersonal relationships (p 0.875>α 0.05) and incentives (p 0.324>α 0.05) in the posyandu immunization program. The conclusion is that, knowledge, motivation and infrastructure are related to the activeness of posyandu cadres while interpersonal relationships and incentives are not related to the activeness of posyandu cadres in the immunization program in Sudirejo I village, Medan City.
The Effectiveness of Government Policy on the Mental Health of Toxic Relationship Victims
Authors: May Nazwa , Handayani Trini , Amalia Mia , Mulyana Aji
Published: November 2024

Toxic relationships can manifest in various connections between partners, friends,
colleagues, and even family members. These detrimental relationships have the potential
to disrupt individuals' mental health, well-being, and productivity. Therefore, the
government must implement substantial policies to address this issue and make
individuals aware of its severity to mitigate negative stigmas. This research aims to
assess how toxic relationships impact the mental health of first-semester students at the
Faculty of Law, Suryakancana University. It is anticipated that the findings of this
research will offer valuable insights for government development of preventive and
intervention strategies. Additionally, this study seeks to raise public awareness
regarding the significance of maintaining healthy relationships and the adverse effects
of toxic relationships on mental health. Through this increased awareness, it is hoped
that the stigma associated with mental health disorders will diminish, and individuals
will be more inclined to seek assistance when needed. The research employs both
qualitative and quantitative methods.
EVALUATING TELEMEDICINE UTILIZATION IN THE NATIONAL HOSPITAL USING RESOURCE PARAMETERS BASED ON THE AUSTRALIAN COUNCIL ON HEALTH CARE STANDARDS (ACHS)
Authors: Heenderi Hendera , Setianto Budhi , Adriansyah Agus Aan
Published: November 2024

Digital transformation and disruptive innovation describe a comprehensive reorientation of industry including its business models due to the arrival of the digital technology era in the form of digitization of products, services and processes. Meanwhile, digital health products can be in the form of electronic health. The low utilization of Telemedicine visits is 2.90% of total visits as well as the conformity of NH Apps telemedicine products with ACHS standards. Analyzing the use of Telemedicine from Resource Parameters based on Australian Council on Healthcare Standards (ACHS) Standards at the National Hospital. The method for this research uses system theory (Input, Process and Output) and is descriptive research with a qualitative approach. By gathering information from 33 respondents who carried out analysis and assessment regarding the implementation of telemedicine in accordance with ACHS. Information that all telemedicine implementation in each department is going well except in the pharmacy department which is considered less good. The implementation of Telemedicine is in accordance with and meets the requirements in terms of the Use of Telemedicine Applications from the Australian Council on Healthcare Standards (ACHS) Requirements Aspect. Process Flow for Using Telemedicine in Hospitals. National Hospital Surabaya is running well and is systemized using the NH Apps application, divided into 2, namely the outpatient flow and the emergency treatment flow. Resources for Using Telemedicine Applications in Hospitals. National Hospital Surabaya has strong modalities regarding units and doctors are all involved in integrated services and have good assessments in system quality, information quality, service quality, structure and environment:
EFFECT OF GARLIC POWDER (ALLIUM SATIVUM LINN) ON REDUCING THE SIGN AND SYMPTOMS OF PULMONARY TUBERCULOSIS
Authors: Retno Retno Twistiandayani , Istiroha  , Lajuward Akhmat Imam
Published: November 2024

Garlic contains substances that function as broad-spectrum antimicrobials that can inhibit the bacteria that cause Tuberculosis (TB). The purpose of this study was to explain the effect of providing garlic powder (Allium Sativum Linn) on reducing the signs and symptoms of pulmonary TB. This study was a quasi-experimental study using a control group pre-posttest design approach. The population of this study were all patients with pulmonary TB at Metatu Health Center, Benjeng, Gresik. The purposive sampling technique was used to recruit respondents and obtained 22 respondents who were divided into treatment groups and control groups. The treatment group received 5gr of garlic powder 3x/day. The instruments used were standard operational procedure and observation sheets for signs and symptoms of pulmonary TB. Data analysis using Paired T-Test test with α < 0.05. The statistical test results obtained p value = 0.000 which means that there was a significant difference in the decrease in signs and symptoms of pulmonary TB before and after the administration of garlic powder. The results of statistical tests in the control group obtained p value = 0.341, which means that there was no significant difference in reducing signs and symptoms of pulmonary TB in the control group. The allicin compound in garlic is able to inhibit the bacteria that cause tuberculosis. The health center is expected to make Standard Operational Procedure related to complementary nursing by giving garlic powder to patients with pulmonary TB.
Revisioning Healthcare in a Different Key
Authors:   Franciscan Hospital System, Rensselaer, USA, Ungar-Sargon Julian
Published: November 2024

After decades working in the field of chronic degenerative neurological disorders I turned my attention to interventional pain
management strategies in an effort to become more effective as a
healer. I discovered that the same intangible issues were behind the
symptoms of acute pain disorders as were chronic and that the human dimension of pain and suffering and the human experience of
disease was as much a factor in the diagnostic and healing process
of chronic as much as acute processes. Nowhere more did I discover these factors than in the chronic disorder known as PTSD. Here,
in seeing my brothers-in-arms in the military as well as in civilian
practice, the influence of past trauma, and the coping mechanisms
learned or inherited, played as important a role in predicting outcome as any intervention, physical or psychological.
Mathematical problem-solving ability of Information Technology Faculty students through a realistic approach
Authors: Puspitasari Wahyu Dwi , Febrinita Filda , Rahma Ika Ayu Nur
Published: November 2024

Computer Systems study program students have a low understanding of the material. The mid-term and final exam scores show the level of students' understanding is still low. In addition, the results of previous research also show that students have difficulty completing mathematical calculations. The purpose of this study is to describe students' problem-solving abilities. The research method used is the descriptive method. The instrument used for data collection was a problem-solving ability question developed with a realistic approach. Three validators have validated this problem-solving question, and small-scale testing has stated that the results are valid and reliable. The study results show that 35.71% of students got a good category, 28.57% got the sufficient category, 7.15% got a less category, and 28.57% got the very less category. Aspects of problem-solving abilities that still need to be improved are planning problem-solving, solving problems according to plan, and re-checking the procedures and results of the solution. From the results of this study, applying the problem-solving learning model with a realistic approach to improve students' problem-solving abilities can be done for further research.
PERANCANGAN VISUAL BRANDING DESA WISATA SITALANG DALAM MEMBENTUK IDENTITAS DESTINASI BERBASIS EKOWISATA
Authors: Triyono Agus - , Yudha Satria Candra , Indriyani Heni , Adham Muhammad Afif Ridwan
Published: November 2024

Pada masa kini sebuah desa berlomba-lomba untuk menunjukkan ja? dirinya sebagai desa wisata. Berkunjung ke wisata alam seper? di desa yang dikemas sedemikian rupa menjadi tren masa kini dengan menjual nilai keindahan alam tak tergan?kan. Wisata agro Sitalang adalah sebuah kawasan yang sangat menarik untuk dikunjungi. Karena berada disepanjang hamparan sawah yang sangat indah. Se?ap akhir pekan akan menjadi magnet baru yang banyak dikunjungi banyak kalangan dari anak-anak,dewasa hingga orang tua. Keunikan dan keindahan alam yang natural ini, menarik untuk di-branding dan dipromosikan pada masyarakat luas dalam berbagai platform media, termasuk media visual dan online. Peneli?an ini dilakukan untuk memberikan solusi terhadap permasalahan yang ada pada iden?tas agrowisata Sitalang melalui visual branding. Visual branding ini mencakup perancangan logo dan juga beberapa media pendukung seper? billboard, seragam, maskot, merchandise, dan juga x-banner. Pada dasarnya perancangan ini bertujuan untuk menciptakan citra berupa iden?tas visual dikarenakan saat ini agrowisata Sitalang belum memiliki citra yang hendak disampaikan kepada audiens. Perancangan visual branding agrowisata Sitalang ini menggunakan pendekatan kualita?f sebagai metode pengumpulan datanya. Data diperoleh peneli? dengan melakukan observasi, wawancara, dan focus group discussion,dokumentasi . Untuk acuan perancangan logo menggunakan pendekatan teori dari David E. Carter, yang menyebutkan bahwasanya logo itu harus merepresentasikan perusahaannya. Setelah itu logo diaplikasikan pada beberapa media pendukung serta penambahan iden?tas berupa maskot untuk memperkuat citra agrowisata Sitalang.
MOTIF BATIK KAMPUNG POERBA SEBAGAI REFLEKSI INDIGENOUS KNOWLEDGE UNTUK PENGEMBANGAN SITUS GEOHERITAGE
Authors: Zulfiningrum Rahmawati , Kumalasari Astini , Hanulis Swastika Muhammad Hafiz Futura , Darma Wahana Mohammad Aka
Published: November 2024

Galuhtimur merupakan desa tempat ditemukannya situs purbakala. Ragam motif batik dari desa ini merupakan refleksi indigenous knowledge yang berasal dari fosil hewan purba dan potensi alam setempat. Riset ini bertujuan mengkaji motif, menganalisis makna filosofis dan refleksi nilai-nilai kehidupan dari batik poerba. Penelitian ini menggunakan teori simbolisme dan metode ikonografi yang memiliki tiga tahap yaitu deskripsi pra-simbolis, analisis simbolisme, dan interpretasi simbolis. Pendekatan kualitatif, wawancara serta observasi diterapkan untuk memperoleh pemahaman mendalam tentang batik poerba. Hasil penelitian menunjukkan bahwa Batik Poerba lahir dari refleksi indigenous knowledge masyarakat desa Galuhtimur. Motif makna dan filosofi pada motif batik Kampung Poerba yaitu: Gajah Poerba: kegagahan dan keberanian, Bunga Katarak: keelokan alam dan keindahan, Gajah Wong: kearifan dan sifat rendah hati, Kerang Poerba: keanggunan, Lereng Poerba: perpaduan dari empat motif sebelumnya yang menggambarkan kegagahan, keelokan, kearifan dan keanggunan. Batik poerba tidak hanya memperkaya warisan kultural namun juga memperkuat ekonomi dan identitas sosial masyarakat Galuhtimur. Mengenalkan batik poerba kepada masyarakat luas merupakan bagian dari upaya mendukung pengembangan wisata edukasi di situs geoheritage serta pelestarian budaya berkelanjutan.
DESAIN KARAKTER ANIMASI 2D “NYURABI KUY!” SEBAGAI MEDIA INFORMASI JAJANAN TRADISIONAL SURABI BANDUNG
Authors: Afif Riky Taufik , Putri Rifa Yoly , Sumarlin Rully
Published: November 2024

Indonesia memiliki sejumlah makanan olahan lokal pada setiap daerahnya resep yang digunakan dan turun dari generasi ke generasi selanjutnya. Salah satunya ialah jajanan tradisional surabi Bandung. Pedagang jajanan tradisional yang berjualan pun datang dari berbagai macam kalangan. Mulai dari pemuda hingga orang dewasa, laki-laki dan perempuan, serta asal daerah pedagang yaitu dari dalam dan juga dari luar Bandung. Tak hanya pedagang yang berdatangan dari berbagai macam kalangan, namun juga pembeli yang mayoritas datang dari kalangan generasi muda. Yaitu kalangan yang berusia 16 sampai 30 tahun. Desain karakter dibuat untuk mewadahi media informasi yang disampaikan melalui karya animasi 2D Nyurabi Kuy! sebagai media informasi jajanan tradisional Surabi Bandung. Desain karakter yang dibuat menyampaikan informasi melalui narasi dan dialog juga acting yang ada pada animasi Nyurabi Kuy!. Metode penelitian yang digunakan adalah metode penelitian kualitatif deskriptif. Metode yang digunakan untuk merancang desain karakter adalah menggunakan metode observasi dan menggunakan style cartoon untuk perancangan karakternya. Atribut dan bentuk anatomis dari karakter menyesuikan dengan hasil observasi lapangan yang penulis lakukan. Pedagang dan juga generasi muda memiliki kaitan erat satu sama lain yaitu sebagai produsen dan juga konsumen. Perancangan desain karakter Animasi 2D berjudul “Nyurabi Kuy!” dibuat dan juga dikembangkan sesuai dengan data dan hasil observasi yang telah dilakukan. Hasil dari perancangan tersebut merupakan sebuah karakter animasi 2D untuk memberikan sebuah solusi dalam media informasi dengan pembawaan jajanan tradisional khas Bandung yaitu Surabi Bandung. Karya desain karakter yang dibuat dapat dikembangkan lagi sebagai IP untuk media lain seperti game yang bertujuan memberikan media informasi tentang surabi Bandung.
Treatment options for odontogenic maxillary sinusitis
Authors: Karpishchenko Sergei , Zubareva Anna , Bolozneva Elizaveta
Published: November 2024

The article discusses modern approaches to the treatment of odontogenic maxillary sinusitis, which is one of the common dental diseases. Special attention is given to the pathogenesis of this condition and the influence of dental infections on the development of sinusitis. Both conservative treatment methods, such as antibacterial and anti-inflammatory therapy, and surgical interventions, including sinusostomy and drainage, are examined. Clinical cases and treatment outcomes are analyzed, allowing for the identification of the most effective strategies in managing this pathology. In conclusion, the importance of an interdisciplinary approach in the diagnosis and treatment of odontogenic maxillary sinusitis is emphasized.
Comparison of uremic toxin removal between expanded hemodialysis and high volume online hemodiafiltrations in different modes
Authors: Biedunkiewicz Jan , Zakrzewska Agnieszka , Małgorzewicz Sylwia , Komorniczak Michał , Jasiulewicz Katarzyna , Płonka Natalia , Tarasewicz Agnieszka , Jankowska Magdalena , Biedunkiewicz Bogdan , Dębska‐Ślizień Alicja , Tylicki Leszek
Published: November 2024

Various high-efficiency hemodialysis techniques exist, including different online high- volume hemodiafiltration (HDF) modes and expanded hemodialysis (HDx) utilizing dialyzers with medium cut-off (MCO) membranes. This study aimed to evaluate the efficacy of uremic toxin removal among four modalities: (I) HDx, (II) pre-dilution HDF (PRE-HDF), (III) mixed-dilution HDF (MIX-HDF), and (IV) post-dilution HDF (POST-HDF), each applied for 1 week in a randomized order. This research was a single-center, prospective, open-label, exploratory crossover study. The reduction ratio (RR) for small molecular toxins (urea and phosphate), a middle molecular toxin (beta-2-microglobulin, β2M), a large-middle molecular toxin (Chitinase-3-like protein 1, YKL-40), and a protein- bound uremic toxin (indoxyl sulfate, IS) was evaluated during a single mid-week dialysis session. Twelve patients were included, with an average age of 52.5 ± 15.47 years and an average dialysis duration of 42.05 ± 31.04 months. The dialysis parameters, including; post-dialysis weight, session duration, dialysate composition, blood and dialysate flow; rates, dialysate temperature, and anticoagulation dosage, were maintained consistently across all modalities. No significant differences in RR for urea, phosphate, β2M, YKL-40, and IS were observed between the treatments. Although the highest IS clearance, though not statistically significant, was observed with POST-HDF and HDx, the differences were not substantial enough to favor any particular modality as the most effective.
The effects of charring on morphology and stable carbon and nitrogen isotope values of common and foxtail millet grains
Authors: Teira-Brión Andrés , Stroud Elizabeth , Charles Michael , Bogaard Amy
Published: November 2024

Stable isotopes are a core method for assessing crop growing conditions in different climatic and soil environments and, thereby, for understanding past agricultural practices. However, isotopic values in plants are altered depending on distinct forms of preservation, including degrees of charring. To investigate this issue in two cereals, common millet (Panicum miliaceum L.) and foxtail millet [Setaria italica (L.) P.Beauv.], we conducted experimental charring to address key questions in millet agriculture and archaeological grain preservation. The results of the experiment under relevant and controlled conditions of charring establish that the relevant temperatures for well-preserved millets occur between 230°C and 250°C and through short-term exposures of up to 6 h of charring. The data confirm that charring increases δ13CVPDB and δ15NAIR values in both common millet and foxtail millet. Husked grains had consistently lower δ13C values than huskless grains, indicating a differential effect of charring on husks and grains, whereas δ15N values are similar regardless of husks. Stable carbon isotope values are relatively similar in uncharred and charred grains, whereas the effects of charring on stable nitrogen isotope values are greater and need to be taken into account when interpreting the values of archaeological grains and palaeodietary analysis in conjunction with human and faunal values. This study significantly advances the understanding of the isotopic effects on archaeological charred grains of common and foxtail millet within their optimal heating preservation window.
Enhancing multimodal literacy through community service learning in higher education
Authors: de Oliveira Janaina Minelli
Published: November 2024

This Curriculum, Instruction, and Pedagogy (CIP) article outlines the pedagogical design of a course that uses Community Service Learning (CSL) to foster undergraduate students' multimodal literacy development. The article draws on a social semiotics approach to learning and communication and aligns with progressive pedagogical designs that prioritize learners' active participation. The course syllabus, methodological procedures, and assessment strategies are described. CSL serves as a means for higher education teachers to embrace civic and social responsibilities, promoting values such as solidarity and generosity through their teaching. This article examines the challenges and benefits associated with CSL and offers insights to inspire higher education teachers to adopt pedagogical designs based on creativity, solidarity, and generosity.
Serum exocrine pancreas enzymes are biomarkers of immunotherapy response in new-onset type 1 diabetes
Authors: Bruggeman Brittany Sorensen , Gornisiewicz Savanna , Bacher Rhonda , McGrail Kieran , Campbell-Thompson Martha , Wasserfall Clive , Jacobsen Laura M. , Atkinson Mark , Haller Michael J. , Schatz Desmond A.
Published: November 2024

Introduction

The immune-mediated destruction of insulin-producing β-cells characterizes type 1 diabetes. Nevertheless, exocrine pancreatic enzymes, including amylase, lipase, and trypsin, are also significantly reduced in type 1 diabetes. With an immunotherapy now approved to treat early-stage type 1 diabetes, biomarkers to delineate response to treatment are needed. No study has yet evaluated whether serum exocrine pancreatic enzymes could delineate immunotherapy responders and non-responders.

Methods

In this novel study, we sought to identify longitudinal trends in the most commonly measured circulating exocrine enzymes before and after treatment with anti-thymocyte globulin (ATG) and pegylated granulocyte colony-stimulating factor (GCSF) in individuals with new-onset type 1 diabetes (n=34). We defined response to immunotherapy as participants with at least 60% of baseline area under the curve (AUC) C-peptide levels after a 2-hour mixed meal tolerance test (MMTT) at two years post-treatment. In the overall study (n=89), 42% of treated and 17% of placebo participants met this definition. Due to constraints of sample availability, we compared longitudinal serum amylase, lipase, and trypsin levels in a subset of responders to therapy (n=4-6), placebo “responders” (n=2), treated non-responders (n=16), and placebo non-responders (n=10).

Results

There were no differences in amylase levels between groups at baseline or six months post-treatment. Baseline levels of lipase and trypsin tended to be lower in responders; however, these variations were not significant in this small study sample. Lipase and trypsin improved to 115% of baseline in responders to immunotherapy six months after treatment and declined to 80-90% of baseline in non-responders and placebo participants (p=0.03). This difference was not present before the six-month time point.

Discussion

Our findings provide preliminary evidence that the exocrine pancreatic enzymes lipase and trypsin may be useful biomarkers of response to immunotherapy in type 1 diabetes. Further studies with larger numbers of participants are warranted.
Detection of gene variants associated with recessive limb–girdle muscular weakness and Pompe disease in a global cohort of patients through the application of next-generation sequencing analysis
Authors: Bevilacqua Jorge Alfredo , Al-Salti Abdullah Mohammed , Al Madani Abubaker , Alves da Fonseca Armando , Durmus Hacer , Chai Josiah , Alshehri Ali , Ribeiro Márcia Gonçalves , Sgobbi Paulo , Nikitin Sergey S. , Vargas Steven , Furtado Adriana , Thibault Nathan , Araujo Roberto , Daba Nadia
Published: November 2024

Introduction

Hereditary myopathies arise due to numerous pathogenic variants occurring in distinct genes, which amount to several hundred. Limb–girdle muscular dystrophies (LGMDs) constitute a heterogeneous group of neuromuscular disorders involving more than 30 genes. Clinically, LGMD is characterized by limb–girdle muscular weakness (LGMW). Late-onset Pompe disease is an important disorder with a differential diagnosis for LGMD, where next-generation sequencing (NGS) plays a crucial role in accurate and prompt diagnosis. The sensitivity and specificity of a 10-gene NGS panel have been previously evaluated for the prevalent forms of recessive LGMD (LGMD-R) and Pompe disease in Latin American patients with LGMW of unknown cause. This project aims to identify the regional relative prevalence of frequent LGMD-R subtypes and Pompe disease in a larger geographic area and to diagnose patients with LGMW by identifying genetic variants of LGMD-R and Pompe disease.

Methods and Results

This 21-country multicentric analysis enrolled 2,372 patients with LGMW from 2017 to 2018. Sequencing analysis was performed using the Illumina NextSeq 500 system, and variant interpretation was performed according to the American College of Medical Genetics and Genomics guidelines. Pathogenic or likely pathogenic variants were seen in 11% of patients (n = 261). Among the positive cases, NGS effectively diagnosed 86.2% and 13.8% of patients with LGMD and Pompe disease, respectively. The most prevalent pathogenic acid α-glucosidase (GAA) variant identified was c.-32-13T > G.

Conclusion

The study adds to the knowledge of the relative occurrence of various subtypes of LGMD worldwide. The inclusion of GAA in the NGS panel to investigate patients with LGMW is a powerful diagnostic approach to screen for late-onset Pompe disease.
Novel pathogenic ATM mutation with ataxia-telangiectasia in a Chinese family
Authors: Zhou Qiaomin , Chen Minling , Tao Enfu
Published: November 2024

Ataxia-Telangiectasia (A-T) is a rare, autosomal recessive disorder characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia, immunodeficiency, and increased cancer risk. Mutations in the ATM gene, which is essential for DNA damage repair, underlie this condition. This study reports a novel homozygous frameshift mutation (ATM_ex20 c.3062delT, p. Val1021fs) in a Chinese family with two affected siblings. The mutation, located in exon 20, has not been previously documented, expanding the spectrum of ATM mutations. The proband and her older sister presented with classic A-T symptoms, including gait instability and conjunctival telangiectasia. Both siblings presented with immunodeficiency, characterized by low immunoglobulin A (IgA) levels, slightly elevated IgM levels, and elevated alpha-fetoprotein (AFP). Cranial magnetic resonance imaging (MRI) findings revealed cerebellar atrophy and cerebral white matter lesions in both sisters. Interestingly, while both sisters shared the same mutation, their clinical severity differed, highlighting the complexity of genotype-phenotype correlations in A-T. The parents and an unaffected sister were heterozygous carriers, consistent with autosomal recessive inheritance. This study underscores the importance of genetic testing in A-T diagnosis and provides new insights into the genetic diversity of ATM-related diseases. Further research is needed to understand the broader implications of this mutation.
Exome sequencing in 90 children with developmental delay: a single-center experience
Authors: Boyarchuk Oksana , Volianska Liubov , Smashna Olena , Makukh Halyna
Published: November 2024

Introduction

Developmental delay (DD) in children is often caused by genetic abnormalities, which are challenging to diagnose due to the vast genetic variability.

Methods

This study presents a detailed analysis of whole-exome sequencing (WES) on 90 children with DD at a single clinical center.

Results

We identified pathogenic or likely pathogenic variants in 27.8% of cases, with 7.8% revealing variants of uncertain significance (VUS). Among the positive findings, 21 (84.0%) corresponded to the main clinical manifestations in patients, and 4 (16.0%) secondary findings provided new insights into the patient’s conditions. Positive and inconclusive cases led to a revision of the diagnosis or management plan in 34.4% of cases. The positive genetic result in children with Developmental delay was higher in the presence of epilepsy or seizures (odds ratio – 5.4444; 95% CI 2.0176 to 14.6918; p = 0.0008) and more than 3 dysmorphic features (odds ratio – 7.1739; 95% CI 1.7791 to 28.9282; p = 0.0056). Variants compatible with the clinical manifestations were identified in 11.9% of children with autistic spectrum disorders.

Conclusion

Our findings emphasize the utility of WES in clinical diagnostics, offering significant insights into patient management and potentially guiding therapeutic decisions.
Effective inhibition of dengue virus replication using 3′UTR-targeted Vivo-Morpholinos
Authors: Niu Mengwei , Yi Wenyanbo , Dong Zhuofan , Li Xiaofeng , Dong Xue , Yu Lifang , Han Yao , Zhang Oujia , Sheng Ziyang , An Jing , Li Hao , Sun Yansong
Published: November 2024

Introduction

Due to the impact of antibody-dependent enhancement and viral variation, effective vaccines or antiviral therapies remain lacking for the dengue virus (DENV). Nucleic acid drugs, particularly Vivo-Morpholinos (MOs), have emerged as a promising avenue for antiviral treatment due to their programmability and precise targeting, as well as their safety and stability.

Method

In this study, we designed and developed 10 morpho-modified (octa-guanidine dendrimer) vivo-MO molecules that target each coding gene of DENV. Subsequently, we assessed the inhibitory impact of vivo-MOs on dengue viral RNA load utilizing qRT-PCR. Furthermore, we examined the inhibitory effect on the live virus through a plaque assay and the TCID50 assay.

Results

We found that the vivo-3′UTR molecule targeting the 3′ untranslated region of the dengue virus exhibited the highest inhibitory rate against viral load. The vivo-3′UTR demonstrated 99% inhibition of dengue virus RNA and the inhibition of up to 98% of the live virus. Additionally, the targeted sequence was conserved among all four DENV serotypes, and treatment with 10 μM of vivo-3′UTR resulted in a reduction of viral titers for all four DENV serotypes by over 99.99%. Additionally, we revealed that pre-treatment with vivo-3′UTR had a notable preventive effect against viral infection.

Conclusion

This study screened an effective vivo-MO target drug for the treatment of dengue virus infection, demonstrating low toxicity in mammalian cell lines, and proposed a novel preventive antiviral approach.
Beach erosion and typhoons reduce green turtle nesting grounds on the Xisha Islands, South China Sea
Authors: Zhang Ting , Zhang Chenglong , Li Yupei , Yu Yangfei , An Xiaoyu , Jiang Yongkang , Wang Jichao , Lin Liu , Shi Hai-Tao
Published: November 2024

Introduction

Sea turtles are ideal flagship and umbrella species for marine biodiversity conservation. The quality of nesting grounds is crucial for the successful reproduction of sea turtles, as it determines whether they can successfully nest and hatch. The Xisha Islands represent the largest remaining nesting grounds for green turtles in China. However, they face numerous threats and lack management guidelines for nesting ground restoration.

Methods

In this study, we continuously monitored the beach changes and coastal erosion on North Island, which is located in the northern region of the Xisha Islands, from 2019 to 2022.

Results

From 2020 to 2022, the beach area on North Island decreased annually by 11,800 m2, accounting for 24.39% of the beach area in 2020. The proportion of suitable nesting sand types (including coarse and medium sands) also decreased annually, with a reduction of 40–70% on the southern beach of North Island. The peak nesting period of green turtles on North Island coincides with the frequent occurrence of typhoons in the South China Sea, causing tidal surges that inundate green turtle nests, resulting in an average nest loss rate of 35.25%.

Discussion

Based on the above threats, it is recommended to promptly initiate habitat restoration in severely eroded areas of green turtle nesting grounds to prevent further declines in nesting area and quality. Additionally, measures such as nest relocation should be implemented to enhance green turtle reproductive success.
Three new species of Gymnopus and Mycena (Agaricales, Basidiomycota) from Northwestern China
Authors: Fan LongFei , Wang BiYue , Ma TianFu , Li Bin , Ma JianWei , Lei XuTao , Bao NingHui
Published: November 2024

Members of the genera Gymnopus and Mycena are vital for litter decomposition in tropical and humid temperate forests. In this study, the difference in morphological features among Gymnopus gansuensis, Gymnopus subsepiiconicus, and Mycena glabera was confirmed by DNA data. Gymnopus gansuensis and Gymnopus subsepiiconicus showed separate relationships with other species in the ITS and nLSU combined dataset utilized for the phylogeny of Gymnopus sect. Impudicae. In addition, Gymnopus gansuensis is characterized by pileus honey yellow at the center, margin pinkish buff to buff, stipe pinkish buff to fuscous, and basidiospores elliptic to briolette. Gymnopus subsepiiconicus is characterized by pileus clay buff to grayish brown at the center, margin pinkish buff to fawn, stipe dark brown to fuscous, and basidiospores elliptic. Based on the combined dataset of the ITS and TEF-1α, Mycena glabera has been detected as a separate lineage in the phylogenetic studies of Mycena sect. Calodontes. The ecological behaviors of the new species are described with illustrations.
The triglyceride-glucose index and risk of cognitive impairment: a systematic review and meta-analysis with inclusion of two national databases
Authors: Yang Ying , Peng Pai , Huang Huadong , Zhao Yanan , Li Yating , Xu Xiao , Jiang Shixie , Yang Yanrong , Pan Gaofeng , Wen Yanting , Wu Dan , Chen Shanping , Feng Lei , Peng Tangming , Wang Jiang , Li Zheng
Published: November 2024

Background

To investigate the relationship between the triglyceride and glucose (TyG) index and cognitive impairment (CI).

Methods

Five authoritative databases were systematically searched for potentially relevant studies on ‘TyG index’ and ‘CI’ from inception to 27 April 2024. Two representative databases from the United Kingdom and United States were also included. We used the PICOS criteria to select available articles. All data was combined to compute Odd Ratios (ORs).

Results

15 studies were included in the meta-analysis (participants: 5604303). The pooled effect sizes demonstrate that individuals with a high TyG index exhibit a significantly elevated risk of CI compared to those with a low TyG index (OR = 2.16, 95%CI: 1.51; 3.08, p < 0.001). The subgroup analysis showed that inpatients with a high TyG index exhibited an increased risk of CI (OR = 4.56, 95%CI: 3.09; 6.74, p < 0.001). Furthermore, the risk of developing distinct types of CI differed significantly [CI: OR = 1.64, 95% CI: 1.29; 2.07, p < 0.001; Vascular Cognitive Impairment (VCI): OR = 5.39, 95% CI: 3.33; 8.70, p < 0.001].

Conclusion

A positive correlation exists between the TyG index and risk of CI, which has potential value in optimizing CI risk stratification among elderly people, especially those hospitalized.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42023450336.
Dynamic graph attention network based on multi-scale frequency domain features for motion imagery decoding in hemiplegic patients
Authors: Wang Yinan , Gong Lizhou , Zhao Yang , Yu Yewei , Liu Hanxu , Yang Xiao
Published: November 2024

Brain-computer interfaces (BCIs) establish a direct communication pathway between the brain and external devices and have been widely applied in upper limb rehabilitation for hemiplegic patients. However, significant individual variability in motor imagery electroencephalogram (MI-EEG) signals leads to poor generalization performance of MI-based BCI decoding methods to new patients. This paper proposes a Multi-scale Frequency domain Feature-based Dynamic graph Attention Network (MFF-DANet) for upper limb MI decoding in hemiplegic patients. MFF-DANet employs convolutional kernels of various scales to extract feature information across multiple frequency bands, followed by a channel attention-based average pooling operation to retain the most critical frequency domain features. Additionally, MFF-DANet integrates a graph attention convolutional network to capture spatial topological features across different electrode channels, utilizing electrode positions as prior knowledge to construct and update the graph adjacency matrix. We validated the performance of MFF-DANet on the public PhysioNet dataset, achieving optimal decoding accuracies of 61.6% for within-subject case and 52.7% for cross-subject case. t-Distributed Stochastic Neighbor Embedding (t-SNE) visualization of the features demonstrates the effectiveness of each designed module, and visualization of the adjacency matrix indicates that the extracted spatial topological features have physiological interpretability.
Medical history of thyroid cancer does not impair prognosis in non-metastatic breast cancer patients: an analysis study based on SEER database and external cohort
Authors: Li Shuai , Chen Xiaosong , Shen Kunwei
Published: November 2024

Background

Non-metastatic breast cancer patients who had a medical history of skin or cervix cancers were presently eligible for clinical trials while few data were available regarding thyroid gland cancer. The study estimated the rate of prior thyroid gland cancer and evaluated its impact on survivals among breast cancer patients.

Methods

Non-metastatic invasive breast cancer patients from the SEER database (SEER cohort) between 2010 and 2019 and Ruijin Hospital (Ruijin cohort) during 2009 and 2019 were retrospectively analyzed. Ascian or Pacific Island patients in the SEER cohort (SEER API cohort) were analyzed separately. Chi-square test and multivariate logistic regression analysis were performed to describe the clinical features. Kaplan-Meier analysis and Cox proportional hazards model were used to compare the overall survival (OS) and breast cancer specific survival (BCSS).

Results

A total of 136,441 patients from the SEER cohort, 17,183 from the SEER API cohort, and 8,079 from the Ruijin cohort were enrolled, of whom 0.68%, 0.81%, and 1.06% had a medical history of thyroid gland cancer, respectively. Patients with prior thyroid gland cancers were significantly older (51-60 years: OR 1.84, 95% CI 1.46-2.30, P < 0.001; 61-70 years: OR 2.00, 95% CI 1.61-2.50, P < 0.001; > 70 years: OR 1.51, 95% CI 1.18-1.92, P = 0.001) and more likely to be API (OR 1.23, 95% CI 1.03-1.48, P = 0.026) versus other races. Multivariate analysis demonstrated that patients with a history of thyroid gland cancer had comparable OS (SEER: HR 0.87, 95% CI 0.68-1.11, P = 0.257; SEER API: HR 0.53, 95% CI 0.22-1.28, P = 0.159; Ruijin: HR 1.07, 95% CI 0.26-4.29, P = 0.811) and BCSS (SEER: HR 0.72, 95% CI 0.49-1.08, P = 0.117; SEER API: HR ∞, 95% CI ∞-∞, P = 0.878; Ruijin: HR 0.70, 95% CI 0.10-4.98, P = 0.750) versus those without primary malignancies in the three cohorts.

Conclusion

There were of a sizable of non-metastatic breast cancer patients with medical history of thyroid gland cancer, which was related with different races. Prior thyroid gland cancer had no adverse impact on clinical outcomes, indicating possible eligible in further clinical trials.
Development and validation of an individualized nomogram for predicting distant metastases in gastric cancer using a CT radiomics-clinical model
Authors: Xue Hui-Bin , Liang Mei-Li , Xu Huang-Zhen , Wang Chen-Yu , Xu Tian-Wen , Zhao Ai-Yue
Published: November 2024

Purpose

This study aimed to develop and validate a model for accurately assessing the risk of distant metastases in patients with gastric cancer (GC).

Methods

A total of 301 patients (training cohort, n = 210; testing cohort, n = 91) with GC were retrospectively collected. Relevant clinical predictors were determined through the application of univariate and multivariate logistic regression analyses. Then the clinical model was established. Venous phase computed tomography (VPCT) images were utilized to extract radiomic features, and relevant features were selected using univariate analysis, Spearman correlation coefficient, and the least absolute shrinkage and selection operator (Lasso) regression. Subsequently, radiomics scores were calculated based on the selected features. Radiomics models were constructed using five machine learning algorithms according to the screened features. Furthermore, separate joint models incorporating radiomic features and clinically independent predictors were established using traditional logistic regression algorithms and machine learning algorithms, respectively. All models were comprehensively assessed through discrimination, calibration, reclassification, and clinical benefit analysis.

Results

The multivariate logistic regression analysis revealed that age, histological grade, and N stage were independent predictors of distant metastases. The radiomics score was derived from 15 selected features out of a total of 944 radiomic features. The predictive performance of the joint model 1 [AUC (95% CI) 0.880 (0.811-0.949)] constructed using logistic regression is superior to that of the joint model 2 [AUC (95% CI) 0.834 (0.736-0.931)] constructed using SVM algorithm. The joint model 1 [AUC(95% CI) 0.880(0.811-0.949)], demonstrated superior performance compared to the clinical model [AUC(95% CI) 0.781(0.689-0.873)] and radiomics model [AUC(95% CI) 0.740(0.626-0.855), using LR algorithm]. The NRI and IDI values for the joint model 1 and clinical model were 0.115 (95% CI 0.014 -0.216) and 0.132 (95% CI 0.093-0.171), respectively; whereas for the joint model 1 and LR model, they were found to be 0.130 (95% CI 0.018-0.243) and 0.116 (95% CI 0.072-0.160), respectively. Decision curve analysis indicated that the joint model 1 exhibited a higher clinical net benefit than other models.

Conclusions

The nomogram of the joint model, integrating radiomic features and clinically independent predictors, exhibits robust predictive capability for early identification of high-risk patients with a propensity for distant metastases of GC.
A comprehensive investigation of PRMT5 in the prognosis and ion channel features of lung cancer
Authors: Wang Yan , Chu Daifang , Li Haichao , Fan Jiangjiang , Zhu Ximing , Ma Yulong , Gu Zhongping , Xie Nianlin , Jing Pengyu
Published: November 2024

The increasing incidence and mortality associated with lung cancer (LC) is a significant global health challenge. The underlying mechanisms contributing to LC remain inadequately understood. However, emerging evidence suggests that the epigenetic modifier protein arginine methyltransferase 5 (PRMT5) plays a complex role in various cellular processes, including DNA repair, gene transcription, and alternative splicing, through its function in catalyzing the symmetric dimethylation of both histone and non-histone proteins. In this study, we examined the functional role of PRMT5 utilizing LC-related datasets (GSE30219, GSE50081, and TCGA LC cohort) through a series of analyses. Our findings revealed that PRMT5 was significantly overexpressed in LC samples compared to normal tissues and was correlated with overall survival and disease-free survival rates. Additionally, PRDM1 was identified as a key protein exhibiting a strong interaction with PRMT5. The prognostic model that integrated PRMT5 with clinical factors demonstrated robust performance in assessing survival outcomes. Elevated levels of PRMT5 were associated with poor prognosis in LC, as evidenced by analyses of the GSE30219, GSE50081, and TCGA-LC datasets. Furthermore, we identified 27 ion channel (IC) genes exhibited a correlation with PRMT5 in lung adenocarcinoma (LUAD), of which 9 genes were identified as statistically significant with KM survival analysis. Strikingly, all of the 9 genes, including LRRC8A, the same as PRMT5, were associated with poor prognosis in LUAD. Our research highlights the potential of PRMT5 as a novel prognostic biomarker and its relationship with IC genes in LC.
Exfoliative esophagitis secondary to tislelizumab: a case report
Authors: Wang Mingxing , Sun Qingming , Dong Wanhui
Published: November 2024

Tislelizumab, as a PD-1 inhibitor, has demonstrated significant efficacy in cancer treatment. However, it may also induce immune-related adverse events (irAEs). This case report describes a patient who developed oral ulcers and dysphagia following treatment with tislelizumab, which was diagnosed as exfoliative esophagitis through endoscopic examination. The condition improved after corticosteroid pulse therapy. A review of the relevant literature revealed no prior reports of immune checkpoint inhibitor (ICI)-related esophagitis cases, prompting an exploration of the potential pathophysiological mechanisms and therapeutic strategies. This report emphasizes the importance of vigilance for rare irAEs during ICI therapy, advocating for early detection and timely intervention.
Pharmacokinetics, pharmacodynamics and bioavailability of dexmedetomidine nasal spray in healthy Chinese adults: A phase I clinical trial
Authors: Li Yan , Qi Lu , Wang Zhenyu , Wang Wan , Zhang Langxi , Yang Leting , Liu Chen , Zhong Wenjing , Wang Xinghe
Published: November 2024

Background

Intranasal administration is a convenient route for drug delivery that can be applied for procedural sedation. However, there is currently limited exploration into fixed dosing regimens. This study was to investigate the pharmacokinetics (PK), pharmacodynamics (PD), bioavailability (BA) and safety of dexmedetomidine after fixed doses of intranasal and intravenous administration in healthy male and female subjects.

Methods

Group A subjects received intranasal or intravenous administration in two periods (12 subjects received intranasal dexmedetomidine (Dex) or the intravenous formulation, and four received the corresponding placebo). Groups B to F underwent single-period dose ascending, receiving only the intranasal Dex formulation or the corresponding placebo (the number of subjects receiving the drug/placebo in groups B to F were 12/2, 12/2, 12/2, 10/2, 10/2, respectively), with doses of 75 μg, 125 μg, 150 μg, 175 μg, and 200 μg, respectively. After administration of each group, blood samples were collected to investigate the plasma concentration of dexmedetomidine, adrenaline and noradrenaline using a HPLC-MS/MS method. Ramsay score, blood pressure and heart rate were collected for safety evaluation. Pharmacokinetic parameters (Cmax, Tmax, AUC0-24h, AUC0–∞, and t1/2) of dexmedetomidine were calculated.

Results

A total of 82 subjects were randomized. One subject withdrew for personal reasons before administration and the other subjects completed the entire study process. At a dose of 25 μg, the absolute bioavailability was 59%. Across the dose range of 25 to 200 μg, the median Tmax was similar (0.5–1 h), and the mean elimination half-life was comparable (3.09–4.28 h), with exposure (Cmax and AUC0-t) increasing with dose. The pharmacokinetics after intranasal spray administration exhibited linear characteristics, although Cmax was similar in the higher dose groups (175 μg and 200 μg). PD results showed that ideal sedation effects (Ramsay score of 3 or higher in at least 90% of subjects) could be achieved within 30 min following intranasal administration of 75 μg or higher doses. All the subjects were well tolerated without any serious adverse events (SAEs).

Conclusion

Dexmedetomidine nasal spray was well tolerated and achieved satisfactory sedation in the dose range of 25–200 μg in Chinese healthy male and female subjects.

Clinical Trial Registration:

http://www.chinadrugtrials.org.cn/, identifier CTR20201650