bluuebunny/crossref_metadata_2025 huggingface dataset:
Knowledge of Direct Oral Anticoagulants (DOACS) and Limits of Their Prescription: Survey of Cardiologists, Intensivists, Neurologists and Pulmonologists in Senegal
Authors: Antoine Sarr Simon , Fatoumata Keita , Fatou Aw , Salvador Mingou Joseph , Youssou Diouf , Rassoul Diop Khadimu , Mor Beye Serigne , Alassane Ngaidé Aliou , Momar Bodian , Bamba Ndiaye Mouhamadou , Alassane Mbaye , Adama Kane , Maboury Diao , Abdoul Kane
Published: April 2024

Introduction: Direct oral anticoagulants (DOACs) constitute a first-line therapy in non-valvular atrial fibrillation and venous thromboembolic disease. The aim of this study was to evaluate the prescription of DOACs among cardiologists, neurologists, intensivists and pulmonologists. Patients and Methods: We conducted a cross-sectional, descriptive study from June 1, 2023 to July 1, 2023, a period of one month. All cardiologists, neurologists, intensivists and pulmonologists who agreed to participate in the study were included. The parameters studied were related to the characteristics of the population, to knowledge and also DOACs prescribing. Data were collected using a pre-established survey questionnaire in paper and electronic format via Google form. Results: We included 218 subjects. Cardiologists were more represented (70.48%). The majority of specialists (70.77%) had between 0 and 5 years of experience. Among the subjects included, 33% claimed to have never had formal training about DOACs. The need for additional training was strongly expressed (85%). We found that 95% prescribed DOACs. The monthly frequency prescription was most often 1 to 2 times (40%). More than 3 out of 10 specialists prescribed DOACs for atrial fibrillation, pulmonary embolism and other situations. The reasons for replacing an AVK with a DOAC were dominated by the problem of compliance with VKAs and the absence of INR control using DOACs (54.7%). The reasons for replacing a DOAC with a VKA were dominated by the high cost of DOAC treatment (77.5%). The limitations of prescribing DOACs were dominated by the high monthly cost (66%), patient preference (14%), and specialist distrust of DOACs (6%). Concerning the compared cost of DOACs versus VKA, 33% of the population considered the cost of DOACs treatment equivalent to that of the overall cost of VKA treatment. Most specialists (99%) stated that their patients were satisfied with DOAC treatment. Conclusion: Direct oral anticoagulants (DOACs) are underused in Senegal due to their high cost but also due to lack of awareness linked to insufficient continuing training.
Prevalence and Sociodemographic Factors Associated With Chronic Intestinal Polyparasitism in Non-Pregnant Adults Living In Urban and Rural Areas of Gabon
Authors: Ada Mengome Meredith Flore , Kono Héléna Néoline , Boulingui Charleine Manomba , M’bondoukwe Noé Patrick , Ndong Ngomo Jacques-Mari , Ditombi Bridy Moutombi , Ngondza Bedrich Pongui , Bisseye Cyrille , Mawili-Mboumba Denise Patricia , Bouyou Akotet Marielle Karine
Published: April 2024

Introduction: Intestinal parasitic infections constitute a major public health problem worldwide. Data from non-pregnant adults are scarce in high burden countries such as Gabon. The present study aimed to determine the prevalence and features of intestinal polyparasitism in urban and rural areas of Gabon. Methods: Apparently healthy volunteers with a microscopic diagnosis of intestinal parasites were included. Sociodemographic and lifestyle characteristics were collected using a written questionnaire. The type and number of detected parasites were also recorded. Statistical analysis was performed using SPSS version 20.0. Results: Among the 239 participants, the prevalence of polyparasitism was 36.4%. The frequencies of protozoa, soil-transmitted helminths (STHs) infections and co-infection (protozoa-STHs) were 35.6%, 46.4% and 18.0%, respectively. Univariate and multivariate analysis showed that polyparasitism was associated with living in rural area (aOR=3.6; 95%CI = 1.0 - 12.1, p = 0.03), female gender (OR = 1.8; 95%CI = 1.0 - 3.2, p = 0.025), the use of non-conventional latrines (aOR = 3.3; 95%CI =1.2 - 9.3, p = 0.02). Drinking river water (aOR = 2.6; 95%CI = 1.1- 6.0, p = 0.024) and living in urban area (uOR = 2.9; 95%CI =1.3 - 6.6, p = 0.007) were significant risk factors of STHs and protozoa carriage, respectively. Conclusion: Polyparasitism is frequent in adults. It is associated with poor sanitary conditions in rural sites. Awareness campaigns and integrated control strategies should also target adult population, which constitutes a significant parasite reservoir.
Transitory Polyglobulia and Low Platelet Count Associated With Pfizer/ Biontech Mrna Vaccine - A Case Report
Authors: Mendel Suchmacher , Mauro Geller
Published: April 2024

The authors report a case of transitory polyglobulia and low platelet count associated with Pfizer mRNA vaccine administration. Upregulation of heme, beta- and gamma-globin synthesis due to activation of NFR2 by IRP/ synthetic mRNA/eIF4E complex and decreased immune-mediated megakaryocytopoiesis and/or peripheral platelet destruction, were hypothesized mechanisms.
Optic Coherence Tomography Angiography in Multiple Sclerosis: A Tool for Evaluation of Neuroinflammation
Authors: Elmas Cansu , Öztürk Mine , Balcı Belgin Petek
Published: April 2024

Purpose: This study aims to evaluate changes in retinal microvasculature in patients with multiple sclerosis (MS) by means of optic coherence tomography angiography (OCTA).

Material and Methods: A total of 60 patients with MS (18 clinically isolated syndrome [CIS], 27 relapsing remitting MS [RRMS], 15 secondary progressive MS [SPMS]) and 56 healthy controls participated in the study. Demographic and clinical data, including optic neuritis history, ophthalmic examination findings, and OCTA parameters, were recorded. OCTA parameters included the following vascular structures: vascular density (VD) in the retinal superficial capillary plexus, deep capillary plexus, and radial peripapillary capillaries. Retinal nerve fiber layer as a structural spectral domain optic coherence tomography parameter was also evaluated.

Results: Superficial and peripapillary vascular plexus densities and retinal nerve fiber layer thickness values were significantly reduced in patients with MS (p=0.0001). Deep capillary plexus densities showed no difference between groups (p=0.279). Patients with a previous history of optic neuritis (ON+) showed significant reduction in VD, compared to patients without a previous history of optic neuritis (ON-), and control groups (p=0.0001). The SPMS group had lower perifoveal values than patients with RRMS and CIS, and patients with RRMS had lower levels than the CIS group (p=0.012; p=0.03; p=0.035). Expanded disability status scores and VD values inversely correlated (r=-0.264; p=0.003). No significant difference between MS and control groups in the foveal avascular zone was found (p=0.296).

Conclusion: OCTA findings showed reduced peripapillary and superficial vascular plexus densities in patients with MS. While this reduction was more prominent in patients with SPMS and history of optic neuritis, patients with CIS and without history of optic neuritis still showed significant reduction compared to healthy controls. These results indicate vascular regression caused by reduced metabolic demand, and microvascular damage caused by chronic inflammation.
Analisis kebutuhan pengembangan E-LKPD untuk meningkatkan ketertarikan siswa dalam proses pembelajaran matematika
Authors: Heriyanto Didi , Rusdi Rusdi , Yantoro Yantoro
Published: April 2024

Penelitian ini bertujuan untuk mengetahui kebutuhan Lembar Kerja Peserta Didik (LKPD) serta untuk mengetahui tanggapan siswa mengenai pengembangan LKPD berbasis elektronik, dan didasari atas banyaknya manfaat yang dimiliki bahan ajar digital dalam bentuk E-LKPD dibandingkan dengan LKPD. Subjek pada penelitian ini adalah siswa SMK Yadika Jambi kelas 1 tahun ajaran 2023/ 2024 yang berjumlah 18 orang dan satu guru matematika di sekolah tersebut. Pengumpulan data penelitian kualitatif ini dilakukan dengan dua cara yaitu pemberian angket respons bagi 18 siswa agar memperoleh tanggapan mengenai kebutuhan lembar kerja dan wawancara bagi satu guru sebagai data deskriptif pendukung untuk membandingkan apakah penilaian yang dilakukan terhadap bahan ajar bersesuaian terhadap angket jawaban siswa. Hasil analisis menunjukkan bahwa respons siswa terhadap pengembangan E-LKPD dinilai cukup baik. Penerapan E-LKPD belum diterapkan di sekolah tersebut dan proses pembelajaran masih bersifat konvensional. Selain itu, peserta didik beranggapan bahwa pengembangan E-LKPD menarik dan edukatif. Oleh karena itu, data hasil analisis kebutuhan ini digunakan sebagai studi pendahuluan untuk mengembangkan E-LKPD yang dapat digunakan.
Examining 8th Grade English Course Outcomes and Reading Passages in the Framework of 21st Century
Authors: Elgün İmgehan , Özkan Neslihan
Published: April 2024

The aim of this study is to evaluate the 8th grade English lesson learning outcomes and the ontent of reading texts within the scope of 21st century skills. Document analysis, was determined as the research method. P21 21st century learning framework was used as a data collection tool and the data were analyzed by using descriptive analysis. The results of the research revealed that students' critical thinking, communication and collaboration skills were supported the most through learning outcomes. In terms of reading texts, communication, collaboration and entrepreneurship skills are mostly supported. In addition to all these, it was concluded that the distribution of the skills in both learning outcomes and reading texts differs according to language skills. On the other hand, in general it has been understood that most of the learning outcomes and reading texts are insufficient to support the development of 21st century skills.
Öğretmen Eğitiminde Lisansüstü Akreditasyon Standart-Gösterge ve Kanıtlarının Belirlenmesi: ‘Lisansüstü Programları Öz Değerlendirme Ekibi’ Standart Alanı
Authors: Elçiçeği Büşra , Yılmaz Kaya
Published: April 2024

Bu araştırma, Türkiye’de lisansüstü programlarında akreditasyon faaliyetinin gerçekleştirilmemesi nedeniyle Eğitim Bilimleri Enstitüsüne bağlı programların lisansüstü akreditasyon standartlarını geliştirmek ve Türkiye’de lisansüstü akreditasyon çalışmalarına katkıda bulunmak amacıyla yapılmıştır. Araştırma nitel ve nicel araştırma yöntemlerinin veri toplama araçları ve veri analiz tekniklerinin ikili kombinasyonu kullanılarak gerçekleştirilmiştir. Araştırma verilerinin toplanmasında doküman incelemesi ve Delphi tekniği kullanılmıştır. Doküman incelemesi kapsamında 12 ülkeden 23 akreditasyon kuruluşunun lisans ve lisansüstü standartları, Avrupa Birliği standartları ve bölgesel akreditasyon kuruluşlarının lisans ve lisansüstü standartları incelenmiştir. Delphi tekniği kapsamında 5’li likert türünde hazırlanan anket araştırmaya katılan 47 uzmanın görüş ve değerlendirmelerine sunulmuştur. Doküman incelemesi tekniği ile elde edilen verilerin analizinde betimsel analiz yöntemi; Delphi tekniği ile elde edilen verilerin analizinde istatistiksel analiz yöntemleri kullanılmıştır. Araştırmadan elde edilen verilerin istatistiksel analizler ile çözümlenmesi sonucunda 8 standart alanına bağlı 88 alt standart hazırlanmıştır. Gösterge ve kanıtların hazırlanma aşamasında ise 7 uzmanın görüşü alınmıştır. Lisansüstü programları öz değerlendirme ekibi standart alanına ilişkin 7 alt standart, 9 gösterge ve 29 kanıt hazırlanmıştır. Bu standart, Delphi tekniğinin ilk turdan itibaren tüm katılımcıların üzerinde uzlaştıkları ve çok fazla değişikliğe uğramayan tek standart alanı olarak ortaya çıkmıştır.
Öğretmen Adaylarının Üstün Yetenekli Öğrencilere Matematik Öğretimi Dersinde Ters Yüz Öğrenme Deneyimleri
Authors: Yılmaz Tuğba Yulet , Gök Mustafa
Published: April 2024

Bu çalışmada son yıllarda popüler olan ters yüz öğrenme modeli kullanılmıştır. Bu çalışmanın amacı, “Üstün yetenekli öğrencilere matematik öğretimi” dersini ters yüz öğrenme modeli ile deneyimleyen ilköğretim matematik öğretmen adaylarının görüşlerini incelemektir. Nitel araştırma desenlerinden fenomenoloji deseni ile tasarlanan bu araştırma, 14 hafta boyunca bir devlet üniversitesinde ilköğretim matematik öğretmenliği programında öğrenim gören 28 öğretmen adayı ile yürütülmüştür. Verilerin toplanmasında yarı yapılandırılmış görüşme tekniği kullanılmış ve veriler içerik analizi ile analiz edilmiştir. Öğretmen adayları yaşadıkları deneyim sonucunda; ters yüz öğrenmenin tanımına, modelin güçlü ve zayıf yönlerine, modelde öğretmen ve öğrenci rollerine, ters yüz öğrenme ile geleneksel öğrenmenin karşılaştırılmasına ilişkin görüşlerini dile getirmişlerdir. Öğretmen adayları modelin güçlü yönü olarak en çok derse hazırlıklı gelme, ders içinde etkinliklere aktif katılma durumuna, zayıf yönü olarak da fazla zaman alması ve teknolojik yetersizlikler olması halinde ders içeriğine erişim sorununa vurgu yapmışlardır. Bu modelde; öğretmenlerin rehber olma rolünün, öğrencilerin ise hem ders öncesinde hem de ders içinde daha fazla sorumluluk üstlenme rolünün ön plana çıktığı belirtilmiştir. Geleneksel modelle karşılaştırıldığında ters yüz öğrenmenin derse ayrılan süreyi genişletmesi sebebiyle daha esnek bir ortamda, daha verimli ve kalıcı öğrenmeler sağladığı, grup çalışmasını gerektirdiğinden akran öğrenmesini teşvik ettiği ve derse yönelik ilgiyi arttırdığı işaret edilmiştir.
Assessing the influence of gastrocnemius reconstruction on stress distribution of femoral tumor rotating hinge knee prosthesis via finite element analysis
Authors: Jiang Jie , Zeng Fanwei , Tang Xiaodong
Published: April 2024

Background:

After femoral oncological knee arthroplasty, some patients suffer from rotating axis fracture, which significantly impacts the life span of the rotating hinge knee (RHK) prosthesis. This research aimed to analyze the biomechanical response of anatomical gastrocnemius reconstruction and assess whether it could reduce the risk of rotating axis breakage by finite element (FE) analysis.

Methods:

A femur-prosthesis-tibia FE model was established using the data from CT scans. The mechanical properties of the RHK implant were quantitatively compared before and after gastrocnemius reconstruction at 6 angles: 10°, 20°, 30°, 40°, 50°, and 60°.

Results:

Our results showed that gastrocnemius reconstruction effectively altered the stress distribution around the rotating axis, considerably relieving the stress in the fracture-prone region. In addition, the peak stress in the rotating axis, bending axis, prosthesis stem, and femoral condyles decreased variably.

Conclusion:

In distal femoral resection knee arthroplasty, the rebuilding of gastrocnemius substantially improved the stress distribution within the prosthesis, thereby having the potential to reduce the risk of prosthetic fracture and prolong the overall durability of the prosthesis.
Case report: Chronic Candida albicans meningitis: a rare entity diagnosed by metagenomic next-generation sequencing
Authors: Kuenzli Andrea B. , Müller Mandy D. , Z`Graggen Werner J. , Walti Laura N. , Martin Yonas , Lazarevic Vladimir , Schrenzel Jacques , Oberli Alexander
Published: April 2024

The aetiology of chronic aseptic meningitis is difficult to establish. Candida meningitis in particular is often diagnosed late, as cerebrospinal fluid (CSF) work-up and imaging findings are nonspecific. A 35-year-old patient with chronic aseptic meningitis, for which repeated microbiological testing of CSF was unrevealing, was finally diagnosed with Candida albicans (C. albicans) meningitis with cauda equina involvement using metagenomic next-generation sequencing (mNGS). This report highlights the diagnostic challenges and the difficulties of treating shunt-associated fungal meningitis.
Phenotypic and genomic characterisation of performance of tropically adapted chickens raised in smallholder farm conditions in Ethiopia
Authors: Morris Katrina M. , Sutton Kate , Girma Mekonnen , Sánchez-Molano Enrique , Solomon Bersabhe , Esatu Wondmeneh , Dessie Tadelle , Vervelde Lonneke , Psifidi Androniki , Hanotte Olivier , Banos Georgios
Published: April 2024

Background:

In sub-Saharan Africa, 80% of poultry production is on smallholder village farms, where chickens are typically reared outdoors in free-ranging conditions. There is limited knowledge on chickens’ phenotypic characteristics and genetics under these conditions.

Objective:

The present is a large-scale study set out to phenotypically characterise the performance of tropically adapted commercial chickens in typical smallholder farm conditions, and to examine the genetic profile of chicken phenotypes associated with growth, meat production, immunity, and survival.

Methods:

A total of 2,573 T451A dual-purpose Sasso chickens kept outdoors in emulated free-ranging conditions at the poultry facility of the International Livestock Research Institute in Addis Ababa, Ethiopia, were included in the study. The chickens were raised in five equally sized batches and were individually monitored and phenotyped from the age of 56 days for 8 weeks. Individual chicken data collected included weekly body weight, growth rate, body and breast meat weight at slaughter, Newcastle Disease Virus (NDV) titres and intestinal Immunoglobulin A (IgA) levels recorded at the beginning and the end of the period of study, and survival rate during the same period. Genotyping by sequencing was performed on all chickens using a low-coverage and imputation approach. Chicken phenotypes and genotypes were combined in genomic association analyses.

Results:

We discovered that the chickens were phenotypically diverse, with extensive variance levels observed in all traits. Batch number and sex of the chicken significantly affected the studied phenotypes. Following quality assurance, genotypes consisted of 2.9 million Single Nucleotide Polymorphism markers that were used in the genomic analyses. Results revealed a largely polygenic mode of genetic control of all phenotypic traits. Nevertheless, 15 distinct markers were identified that were significantly associated with growth, carcass traits, NDV titres, IgA levels, and chicken survival. These markers were located in regions harbouring relevant annotated genes.

Conclusion:

Results suggest that performance of chickens raised under smallholder farm conditions is amenable to genetic improvement and may inform selective breeding programmes for enhanced chicken productivity in sub-Saharan Africa.
The immune landscape of sepsis and using immune clusters for identifying sepsis endotypes
Authors: Tang Guoxing , Luo Ying , Song Huijuan , Liu Wei , Huang Yi , Wang Xiaochen , Zou Siyu , Sun Ziyong , Hou Hongyan , Wang Feng
Published: April 2024

Background

The dysregulated immune response to sepsis still remains unclear. Stratification of sepsis patients into endotypes based on immune indicators is important for the future development of personalized therapies. We aimed to evaluate the immune landscape of sepsis and the use of immune clusters for identifying sepsis endotypes.

Methods

The indicators involved in innate, cellular, and humoral immune cells, inhibitory immune cells, and cytokines were simultaneously assessed in 90 sepsis patients and 40 healthy controls. Unsupervised k-means cluster analysis of immune indicator data were used to identify patient clusters, and a random forest approach was used to build a prediction model for classifying sepsis endotypes.

Results

We depicted that the impairment of innate and adaptive immunity accompanying increased inflammation was the most prominent feature in patients with sepsis. However, using immune indicators for distinguishing sepsis from bacteremia was difficult, most likely due to the considerable heterogeneity in sepsis patients. Cluster analysis of sepsis patients identified three immune clusters with different survival rates. Cluster 1 (36.7%) could be distinguished from the other clusters as being an “effector-type” cluster, whereas cluster 2 (34.4%) was a “potential-type” cluster, and cluster 3 (28.9%) was a “dysregulation-type” cluster, which showed the lowest survival rate. In addition, we established a prediction model based on immune indicator data, which accurately classified sepsis patients into three immune endotypes.

Conclusion

We depicted the immune landscape of patients with sepsis and identified three distinct immune endotypes with different survival rates. Cluster membership could be predicted with a model based on immune data.
The time-dependent changes in serum immunoglobulin after kidney transplantation and its association with infection
Authors: Jo Eun-Ah , Min Sangil , Jo Ae jung , Han Ahram , Ha Jongwon , Song Eun Young , Lee Hajeong , Kim Yong Chul
Published: April 2024

Introduction

Kidney transplant recipients often experience significant alterations in their immune system, which can lead to increased susceptibility to infections. This study aimed to analyze time-dependent changes in serum immunoglobulin and complement levels and determine the risk factors associated with infection.

Methods

A retrospective analysis of serum samples from 192 kidney transplant recipients who received transplantations between August 2016 and December 2019 was conducted. The serum samples were obtained at preoperative baseline (T0), postoperative 2 weeks (T1), 3 months (T2), and 1 year (T3). The levels of serum C3, C4, IgG, IgA, and IgM were measured to evaluate immune status over time.

Results

The analysis revealed significant decreases in IgG and IgA levels at T1. This period was associated with the highest occurrence of hypogammaglobulinemia (HGG) and hypocomplementemia (HCC), as well as an increased incidence of severe infection requiring hospitalization and graft-related viral infections. Using a time-dependent Cox proportional hazards model adjusted for time-varying confounders, HGG was significantly associated with an increased risk of infection requiring hospitalization (HR, 1.895; 95% CI: 1.871–1.920, P-value<0.001) and graft-related viral infection (HR, 1.152; 95% CI: 1.144–1.160, P-value<0.001).

Discussion

The findings suggest that monitoring serum immunoglobulin levels post-transplant provides valuable insights into the degree of immunosuppression. Hypogammaglobulinemia during the early post-transplant period emerges as a critical risk factor for infection, indicating that serum immunoglobulins could serve as feasible biomarkers for assessing infection risk in kidney transplant recipients.
Integrated analysis of the physiological, transcriptomic and metabolomic responses of Neoporphyra haitanensis after exposure to UV-B radiation: an energy metabolism perspective
Authors: Wang Xinyue , Zang Yu , Xue Song , Shang Shuai , Xin Jiayi , Tang Liuqing , Chen Jun , Tang Xuexi
Published: April 2024

The increase in UV-B radiation at the Earth’s surface due to the depletion of the stratospheric ozone layer is a notable facet of contemporary climate change patterns. The macroalgae inhabiting the intertidal zone exhibit a diverse array of adaptive strategies to cope with dramatic environmental changes. In this study, we integrated physiological, transcriptomic and metabolomic data from energy metabolism perspective to elucidate the responses and recovery mechanism of N. haitanensis to UV-B radiation exposure. UV-B radiation has a harmful impact on the photosynthetic performance of N. haitanensis. However, an increase in photosynthetic performance and upregulated expression of genes related to photosynthesis were observed during recovery, suggesting that the effect of UV-B on N. haitanensis was dynamic photoinhibition. Recovery experiments revealed that most genes and metabolites related to glycolysis were significantly upregulated, suggesting that glycolysis was activated to promote energy production. In addition, the TCA cycle was also activated, as evidenced by the increase in key substances and the upregulated expression of key enzyme-encoding genes during recovery. Correspondingly, ATP was also abundantly accumulated. These results suggested that the TCA cycle provided ATP for N. haitanensis to repair UV-B damage. Meanwhile, amino acid metabolism was enhanced during recovery as a source of intermediates for the TCA cycle. Therefore, photosynthesis, glycolysis, the TCA cycle, and amino acid metabolism synergistically cooperate to provide material and energy for recovery after UV-B radiation. This study is important for understanding the adaptive strategies of intertidal macroalgae in response to UV-B radiation.
Immunotherapeutic implications of negative regulation by protein tyrosine phosphatases in T cells: the emerging cases of PTP1B and TCPTP
Authors: Perez-Quintero Luis Alberto , Abidin Belma Melda , Tremblay Michel L.
Published: April 2024

In the context of inflammation, T cell activation occurs by the concerted signals of the T cell receptor (TCR), co-stimulatory receptors ligation, and a pro-inflammatory cytokine microenvironment. Fine-tuning these signals is crucial to maintain T cell homeostasis and prevent self-reactivity while offering protection against infectious diseases and cancer. Recent developments in understanding the complex crosstalk between the molecular events controlling T cell activation and the balancing regulatory cues offer novel approaches for the development of T cell-based immunotherapies. Among the complex regulatory processes, the balance between protein tyrosine kinases (PTK) and the protein tyrosine phosphatases (PTPs) controls the transcriptional and metabolic programs that determine T cell function, fate decision, and activation. In those, PTPs are de facto regulators of signaling in T cells acting for the most part as negative regulators of the canonical TCR pathway, costimulatory molecules such as CD28, and cytokine signaling. In this review, we examine the function of two close PTP homologs, PTP1B (PTPN1) and T-cell PTP (TCPTP; PTPN2), which have been recently identified as promising candidates for novel T-cell immunotherapeutic approaches. Herein, we focus on recent studies that examine the known contributions of these PTPs to T-cell development, homeostasis, and T-cell-mediated immunity. Additionally, we describe the signaling networks that underscored the ability of TCPTP and PTP1B, either individually and notably in combination, to attenuate TCR and JAK/STAT signals affecting T cell responses. Thus, we anticipate that uncovering the role of these two PTPs in T-cell biology may lead to new treatment strategies in the field of cancer immunotherapy. This review concludes by exploring the impacts and risks that pharmacological inhibition of these PTP enzymes offers as a therapeutic approach in T-cell-based immunotherapies.
Incidence and risk factors of age-related macular degeneration in patients with Parkinson’s disease: a population-based study
Authors: Yoon Bora , Sa Ho-Seok , Kim Hwa Jung
Published: April 2024

Background and objective

The association between age-related macular degeneration (AMD) and Parkinson’ disease (PD) remains unclear. The aim of the present study was to assess the incidence of AMD in patients with PD, elucidate differences by age and sex, and investigate potential risk factors for AMD.

Methods

Data were extracted from the Korean National Health Insurance System database, which covers 97% of the Korean population (2002 through 2019). We calculated the incidence of newly diagnosed AMD in patients with PD and used Cox proportional-hazards models to estimate risk factors for AMD, presenting adjusted hazard ratios (aHR) with 95% confidence intervals (CI).

Results

Of 172,726 patients with PD, 15,800 were newly diagnosed with AMD during the follow-up, including 5,624 men and 10,176 women. The overall incidence of AMD in patients with PD was 13.59 per 1,000 person-years. Stratified by age group and sex, the incidence was higher in women aged 40–69, and conversely higher in men aged 70–89. Risk of AMD was high in older age groups (aHR = 4.36, 95% CI: 3.74–5.09 in the 70 s), female sex (aHR = 1.07, 95% CI: 1.04–1.11), patients with diabetes mellitus (DM) (aHR = 1.14, 95% CI: 1.10–1.18), and patients with hyperlipidemia (aHR = 1.17, 95% CI: 1.13–1.21).

Conclusion

Our findings suggest that the AMD incidence is higher in patients with PD than in the general population, with varying patterns of sex differences across age groups. Particularly, old age, female sex, presence of DM, and hyperlipidemia are potential risk factors. Therefore, clinicians should pay greater attention to AMD in patients with PD.
Interaction of functionalized graphene with cellular membranes: an in silico investigation of graphene-based nanovehicle toward biomedical applications
Authors: Gholami Maryam , Zaboli Ameneh , Hashemzadeh Hassan , Shirshahi Vahid
Published: April 2024

Nanomaterials, especially graphene derivatives, have become major tools in the biomedical area. Understanding the way that graphene interacts with component elements of biological systems, like biological membranes, is critical for the development of successful biomedical applications. The interaction mechanism of graphene sheets with a model cell membrane was investigated in this study using molecular dynamics (MD) simulations under three different conditions: pristine graphene (PG), carboxyl group-functionalized graphene (G-COOH), and amine group-functionalized graphene (G-NH2). The MD simulations demonstrated that functional groups on graphene surfaces improve their interaction with the head groups of the membrane. In 200 nanoseconds, PG reached equilibrium outside and near the phospholipid membrane. G-NH2 was positioned away from the model membrane’s surface, while G-COOH and G-NH2 also achieved equilibrium outside the membrane. It was shown by molecular dynamics simulations that after 200 ns, all three systems had attained their stable states. Crucially, it is discovered that the kind of functional groups greatly affected how the nanoparticles and membrane interacted. Each and every nanocarrier has a strong propensity to break through the membrane. The van der Waals interaction energies for the PG, G-NH2, and G-COOH systems were further shown by the obtained data to be roughly −400.66, −397.52, and −876.36 kJ/mol, respectively. These results support the notion that G-COOH interacts with the model cell bilayer more strongly than PG and G-NH2. This work highlights the influence of functional groups on the interaction of graphene sheets with biological membranes, offering important insights into the equilibrium behavior and entry mechanism of graphene sheets in a model cell membrane.
Grid codes vs. multi-scale, multi-field place codes for space
Authors: Dietrich Robin , Waniek Nicolai , Stemmler Martin , Knoll Alois
Published: April 2024

Introduction

Recent work on bats flying over long distances has revealed that single hippocampal cells have multiple place fields of different sizes. At the network level, a multi-scale, multi-field place cell code outperforms classical single-scale, single-field place codes, yet the performance boundaries of such a code remain an open question. In particular, it is unknown how general multi-field codes compare to a highly regular grid code, in which cells form distinct modules with different scales.

Methods

In this work, we address the coding properties of theoretical spatial coding models with rigorous analyses of comprehensive simulations. Starting from a multi-scale, multi-field network, we performed evolutionary optimization. The resulting multi-field networks sometimes retained the multi-scale property at the single-cell level but most often converged to a single scale, with all place fields in a given cell having the same size. We compared the results against a single-scale single-field code and a one-dimensional grid code, focusing on two main characteristics: the performance of the code itself and the dynamics of the network generating it.

Results

Our simulation experiments revealed that, under normal conditions, a regular grid code outperforms all other codes with respect to decoding accuracy, achieving a given precision with fewer neurons and fields. In contrast, multi-field codes are more robust against noise and lesions, such as random drop-out of neurons, given that the significantly higher number of fields provides redundancy. Contrary to our expectations, the network dynamics of all models, from the original multi-scale models before optimization to the multi-field models that resulted from optimization, did not maintain activity bumps at their original locations when a position-specific external input was removed.

Discussion

Optimized multi-field codes appear to strike a compromise between a place code and a grid code that reflects a trade-off between accurate positional encoding and robustness. Surprisingly, the recurrent neural network models we implemented and optimized for either multi- or single-scale, multi-field codes did not intrinsically produce a persistent “memory” of attractor states. These models, therefore, were not continuous attractor networks.
Neutrophil extracellular trap biomarkers in aneurysmal subarachnoid hemorrhage: early decline of DNase 1 activity associated with delayed cerebral ischemia
Authors: Hendrix Philipp , Witsch Jens , Spalart Valérie , Schneider Hauke , Oertel Joachim , Geisel Jürgen , Martinod Kimberly , Hemmer Sina
Published: April 2024

Introduction

High-mobility group box 1 (HMGB1) protein is a critical mediator of neutrophil extracellular trap (NET) formation (NETosis). Myeloperoxidase (MPO)-DNA complexes, a biomarker of NETs, and HMGB1 have been associated with delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Additional mechanistic NET-related biomarkers and their role in the neuroinflammatory cascade surrounding DCI remain to be explored.

Methods

A post-hoc analysis of a prospective, blinded, single-center biomarker observational study was performed. De novo measurements of serum citrullinated histone H3-DNA complexes (H3Cit-DNA), peptidylarginine deiminase 4 (PAD4), cell-free DNA (cf-DNA), and DNase 1 activity were conducted on admission (D0) and day 4 (D4). Delayed cerebral infarction (DCI) was defined as new cerebral infarction on CT head not present on the post-treatment scan.

Results

H3Cit-DNA, PAD4, cf-DNA, and DNase 1 activity were within quantifiable ranges in all serum samples analyzed at D0 and D4. Admission biomarker levels were not associated with DCI development. From D0 to D4, in both the DCI and the non-DCI groups, H3Cit-DNA levels significantly decreased, cf-DNA levels significantly increased, and PAD4 levels remained stable. In contrast, DNase 1 activity significantly decreased from D0 to D4 in the DCI group (p < 0.001) but not in the non-DCI group.

Conclusion

This exploratory analysis demonstrated NET-related biomarkers such as H3Cit-DNA, PAD4, cf-DNA, and DNase 1 activity in all aSAH patients. A decline of systemic DNase 1 activity in the early phase might increase the risk of delayed cerebral ischemia.
Real-world data of tenecteplase vs. alteplase in the treatment of acute ischemic stroke: a single-center analysis
Authors: Yao Yu , Wu Yuefei , Zhang Xiaoqin , Liu Chang , Cai Lingling , Ying Yisha , Yang Jianhong
Published: April 2024

Background

This retrospective observational cohort study aimed to evaluate whether tenecteplase’s use for acute ischemic stroke (AIS) has time management advantages and clinical benefits.

Methods

144 AIS patients treated with alteplase and 120 with tenecteplase were included. We compared baseline clinical characteristics, key reperfusion therapy time indices [onset-to-treatment time (OTT), door-to-needle time (DNT), and door-to-puncture time (DPT)] and clinical outcomes (24-h post-thrombolysis NIHSS improvement, and intracranial hemorrhage incidence) between the groups using univariate analysis. We assessed hospital stay durations and used binary logistic regression to examine tenecteplase’s association with DNT and DPT target times, NIHSS improvement, and intracranial hemorrhage.

Results

Baseline characteristics showed no significant differences except hyperlipidemia and atrial fibrillation. OTT (133 vs. 163.72, p = 0.001), DNT (36.5 vs. 50, p < 0.001) and DPT (117 vs. 193, p = 0.002) were significantly faster in the tenecteplase group. The rates of DNT ≤ 45 min (65.83% vs. 40.44%, p < 0.001) and DPT ≤ 120 min (59.09% vs. 13.79%, p = 0.001) were significantly higher in the tenecteplase group. Tenecteplase was an independent predictor of achieving target DNT (OR 2.951, 95% CI 1.732–5.030; p < 0.001) and DPT (OR 7.867, 95% CI 1.290–47.991; p = 0.025). Clinically, the proportion NIHSS improvement 24 h post-thrombolysis was higher in the tenecteplase group (64.17% vs. 50%, p = 0.024). No significant differences were observed in symptomatic intracranial hemorrhage (sICH) or any intracranial hemorrhage (ICH). Patients receiving tenecteplase had shorter hospital stays (6 vs. 8 days, p < 0.001). Tenecteplase was an independent predictor of NIHSS improvement at 24 h (OR 1.715, 95% CI 1.011–2.908; p = 0.045). There was no significant association between thrombolytic choice and sICH or any ICH.

Conclusion

Tenecteplase significantly reduced DNT and DPT. It was associated with early neurological function improvement (at 24 h), without compromising safety compared to alteplase. The findings support tenecteplase’s application in AIS.
Clinical features of neuronal intranuclear inclusion disease with seizures: a systematic literature review
Authors: Zhang Jinwei , Ling Ling , Xiang Lei , Li Wenxia , Bao Pengnan , Yue Wei
Published: April 2024

Background

Infant, junior, and adult patients with neuronal intranuclear inclusion disease (NIID) present with various types of seizures. We aimed to conduct a systematic literature review on the clinical characteristics of NIID with seizures to provide novel insight for early diagnosis and treatment and to improve prognosis of these patients.

Methods

We used keywords to screen articles related to NIID and seizures, and data concerning the clinical characteristics of patients, including demographic features, disease characteristics of the seizures, treatment responses, imaging examinations, and other auxiliary examination results were extracted.

Results

The included studies comprised 21 patients with NIID with seizures. The most common clinical phenotypes were cognitive impairment (76.20%) and impaired consciousness (57.14%), and generalized onset motor seizures (46.15%) represented the most common type. Compared with infantile and juvenile cases, the use of antiepileptic drugs in adults led to significant seizure control and symptom improvement, in addition to providing a better prognosis. The number of GGC sequence repeats in the NOTCH2NLC gene in six NIID patients with seizures who underwent genetic testing ranged 72–134.

Conclusion

The most common clinical phenotypes in patients with NIID with seizures were cognitive impairment and consciousness disorders. Patients with NIID presented with various types of seizures, with the most common being generalized onset motor seizures. Adult patients had a better prognosis and were relatively stable. The early diagnosis of NIID with seizures is of great significance for treatment and to improve prognosis.
Rotenone-induced PINK1/Parkin-mediated mitophagy: establishing a silkworm model for Parkinson’s disease potential
Authors: Zhang Hantao , Yang Jinyue , Guo Yinglu , Lü Peng , Gong Xun , Chen Keping , Li Xiubin , Tang Min
Published: April 2024

Parkinson’s disease (PD), ranking as the second most prevalent neurodegenerative disorder globally, presents a pressing need for innovative animal models to deepen our understanding of its pathophysiology and explore potential therapeutic interventions. The development of such animal models plays a pivotal role in unraveling the complexities of PD and investigating promising treatment avenues. In this study, we employed transcriptome sequencing on BmN cells treated with 1 μg/ml rotenone, aiming to elucidate the underlying toxicological mechanisms. The investigation brought to light a significant reduction in mitochondrial membrane potential induced by rotenone, subsequently triggering mitophagy. Notably, the PTEN induced putative kinase 1 (PINK1)/Parkin pathway emerged as a key player in the cascade leading to rotenone-induced mitophagy. Furthermore, our exploration extended to silkworms exposed to 50 μg/ml rotenone, revealing distinctive motor dysfunction as well as inhibition of Tyrosine hydroxylase (TH) gene expression. These observed effects not only contribute valuable insights into the impact and intricate mechanisms of rotenone exposure on mitophagy but also provide robust scientific evidence supporting the utilization of rotenone in establishing a PD model in the silkworm. This comprehensive investigation not only enriches our understanding of the toxicological pathways triggered by rotenone but also highlights the potential of silkworms as a valuable model organism for PD research.
Dietary intake and adherence to the Mediterranean diet in semi-professional female soccer players: a cross-sectional study
Authors: Modena Alessandro , Casiraghi Maria Cristina , Erba Daniela
Published: April 2024

Background

Adequate energy and nutrient intakes in athletes contribute to optimal performance and recovery, decrease the risk of injury, and help preserve athletes’ health. The Mediterranean diet (MD) is considered suitable for covering the nutritional needs of athletes, while contributing to improve eating habits. The aim of the present study was to investigate the energy and nutrient intakes of semi-professional female soccer players and their adherence to the MD, during the competitive season.

Methods

A cross-sectional observational study was conducted on twenty-three female soccer players, who were invited to fill in a 3-day food diary twice, one month apart, to assess their energy and nutrient intakes and a validated questionnaire (MEDI-LITE) to evaluate their adherence to MD. Exercise energy expenditure during three training and match-play days was monitored by GPS.

Results

On average, the participants consumed 1,981 kcal/day, with 44% of their energy deriving from carbohydrates, 21% from protein, and 34% from fat; the mean MD adherence score was 10.1 ± 1.8, corresponding to a good MD adherence. A substantial percentage of athletes were at risk of insufficient nutrient intakes for vitamin D (100%), iodine (87%), potassium (87%), vitamin E (39%), iron and zinc (17 and 30%, respectively).

Conclusion

The evaluation of the dietary intake in female soccer players showed energy deficiency in relation to training level, mainly due to the insufficient intake of carbohydrates, and micronutrient deficiencies. The technical staff should promote adequate consumption of starchy foods in female athletes and emphasize the importance of a proper distribution of energy intake among different eating occasions, including snacks. Periodic monitoring of the nutritional status of micronutrients (vitamin D and some minerals) could help reduce deficiency risk. Over all, nutrition education to improve eating habits of athletes seems worthy of attention, in order to preserve athletes’ health and performance.
Case report: Immunotherapy inducing unexpected overall survival in choroidal melanoma: about a case
Authors: Elhaitmy Youssef , El Anssari Soukaina , Fournel Pierre , Mellas Nawfel , Bouleftour Wafa , Lamuraglia Michele
Published: April 2024

Choroidal melanoma (CM) is the most common malignant ocular tumor in adults. The current treatment of metastatic CM is limited by the intrinsic resistance of CM to conventional systemic therapies. Immunotherapy alone or in association with cytotoxic treatment became a realist option treatment. Advancements in molecular biology have resulted in the identification of a number of promising prognostic and therapeutic targets. Herein, we report a rare case of 36-year-old patient with metastatic CM who presented a good long response to treatment with double immunotherapy reaching 3 years of overall survival, which has never been described in the literature.
Differences in the expression of the phosphatase PTP-1B in patients with localized prostate cancer with and without adverse pathological features
Authors: Bourlon Maria T. , Urbina-Ramirez Shaddai , Verduzco-Aguirre Haydee C. , Mora-Pineda Mauricio , Velazquez Hugo E. , Leon-Rodriguez Eucario , Atisha-Fregoso Yemil , De Anda-Gonzalez María G.
Published: April 2024

Introduction

Patients with adverse pathological features (APF) at radical prostatectomy (RP) for prostate cancer (PC) are candidates for adjuvant treatment. Clinicians lack reliable markers to predict these APF preoperatively. Protein tyrosine phosphatase 1B (PTP-1B) is involved in migration and invasion of PC, and its expression could predict presence of APF. Our aim was to compare PTP-1B expression in patients with and without APF, and to explore PTP-1B expression as an independent prognostic factor.

Methods

Tissue microarrays (TMAs) were constructed using RP archival specimens for immunohistochemical staining of PTP-1B; expression was reported with a standardized score (0-9). We compared median PTP-1B score between cases with and without APF. We constructed two logistic regression models, one to identify the independence of PTP-1B score from biologically associated variables (metformin use and type 2 diabetes mellitus [T2DM]) and the second to seek independence of known risk factors (Gleason score and prostate specific antigen [PSA]).

Results

A total of 73 specimens were suitable for TMA construction. Forty-four (60%) patients had APF. The median PTP-1B score was higher in those with APF: 8 (5-9) vs 5 (3-8) (p=0.026). In the logistic regression model including T2DM and metformin use, the PTP-1B score maintained statistical significance (OR 1.21, 95% CI 1.01-1.45, p=0.037). In the model including PSA and Gleason score; the PTP-1B score showed no independence (OR 1.68, 95% CI 0.97-1.41, p=0.11). The area under the curve to predict APF for the PTP-1B score was 0.65 (95% CI 0.52-0.78, p=0.03), for PSA+Gleason 0.71 (95% CI 0.59-0.82, p=0.03), and for PSA+Gleason+PTP-1B score 0.73 (95% CI 0.61-0.84, p=0.001).

Discussion

Patients with APF after RP have a higher expression of PTP-1B than those without APF, even after adjusting for T2DM and metformin exposure. PTP-1B has a good accuracy for predicting APF but does not add to known prognostic factors.
Biomarkers of chemotherapy-induced cardiotoxicity: toward precision prevention using extracellular vesicles
Authors: Silver Brian B. , Kreutz Anna , Weick Madeleine , Gerrish Kevin , Tokar Erik J.
Published: April 2024

Detrimental side effects of drugs like doxorubicin, which can cause cardiotoxicity, pose barriers for preventing cancer progression, or treating cancer early through molecular interception. Extracellular vesicles (EVs) are valued for their potential as biomarkers of human health, chemical and molecular carcinogenesis, and therapeutics to treat disease at the cellular level. EVs are released both during normal growth and in response to toxicity and cellular death, playing key roles in cellular communication. Consequently, EVs may hold promise as precision biomarkers and therapeutics to prevent or offset damaging off-target effects of chemotherapeutics. EVs have promise as biomarkers of impending cardiotoxicity induced by chemotherapies and as cardioprotective therapeutic agents. However, EVs can also mediate cardiotoxic cues, depending on the identity and past events of their parent cells. Understanding how EVs mediate signaling is critical toward implementing EVs as therapeutic agents to mitigate cardiotoxic effects of chemotherapies. For example, it remains unclear how mixtures of EV populations from cells exposed to toxins or undergoing different stages of cell death contribute to signaling across cardiac tissues. Here, we present our perspective on the outlook of EVs as future clinical tools to mitigate chemotherapy-induced cardiotoxicity, both as biomarkers of impending cardiotoxicity and as cardioprotective agents. Also, we discuss how heterogeneous mixtures of EVs and transient exposures to toxicants may add complexity to predicting outcomes of exogenously applied EVs. Elucidating how EV cargo and signaling properties change during dynamic cellular events may aid precision prevention of cardiotoxicity in anticancer treatments and development of safer chemotherapeutics.