bluuebunny/crossref_metadata_2025 huggingface dataset:
ULUSLARARASI KIZILHAÇ KOMİTESİ'NİN ULUSLARARASI İNSANCIL ÖRF VE ADET HUKUKU KURALLARININ TÜRKÇE'YE YENİDEN YORUMU (ÇEVİRİSİ)
Authors: AKDOĞAN Erkan
Published: October 2023

Uluslararası Kızılhaç Komitesi’nin uluslararası insancıl hukukun örf ve adet hukuku kurallarının neler olduğunu ve kuralların gerekçelerini açıklayan çalışması, bunlara paralel olarak, yayınlandığı günden bu yana hem hukukun ne olduğunu bildiren hem de yerine göre hukukun nasıl gelişebileceğine işaret eden benzersiz bir işlev görüyor. Bu benzersiz işleve karşılık olarak çalışmanın parçası olan Kuralların, aralarında Türkçesinin de bulunduğu farklı dillere çevrildiğini görüyoruz. Bu yazıda, Kuralların Türkçe çevirilerinde genel uluslararası hukuka, uluslararası insancıl hukuka ve Komite’ye yönelik olarak yaklaşımımız doğrultusunda, zaman içinde karşılaştığımız kusurları elden geldiğince gidermeye ve anılan çevirileri telif etmeye yönelik çabamızın ürünü olarak Kuralların yeniden yorumunu sunuyoruz. En aşağıda satırlarını okuyacağınız Türkçe’ye yeniden yorum (çeviri); bu çabamızın ürünü olarak, Türkiye’de nitelik ve nicelik olarak artış gösteren uluslararası hukuk ve uluslararası insancıl hukuk doktrinine katkı sağlamak amacı taşıyor. Buna bağlı olarak, aşağıda önce, benimsediğimiz yaklaşım somutlaştırılacak; ardından, izlediğimiz yöntemi ve yöntemin somut sonuçları ve son olarak da Kuralların Türkçe’ye yeniden yorum (çeviri) metni paylaşılacaktır.
Biosignature, Technosignature, Event: Deconstruction, Astrobiology, and the Search for a Wholly Other Origin
Authors: Mastrogiovanni Armando M.
Published: October 2023

Here I pursue a deconstructive reading of astrobiology, the emerging science dedicated to a double quest: solving the mystery of life's origin and discovering life beyond Earth. Astrobiology, I argue, is organized as a response to the aporetic formulation assumed by the origin of life in modern molecular biology, where (as Derrida's argues in Life Death) it becomes the origin of textuality. Because all Earth life shares a single genetic code, astrobiologists are seeking a second; hoping that a sort of multi-planetary comparative genomics may reveal the secret to life's origin. But the aporia repeats in the figure of the biosignature, the trace of life.
Aranose: Domestic original cytostatic agent for treatment of neuroendocrine tumors of all localizations
Authors: Artamonova E. V. , Emelyanova G. S. , Evdokimova E. V. , Markovich A. A. , Gorbunova V. A.
Published: October 2023

Aranose is an original cytostatic, synthesized in the Russian Cancer Research Center, belongs to the class of nitrosourea derivatives (this class of drugs also including streptozotocin). In preclinical trials, Aranose has shown its activity in neuroendocrine tumors (NETs). Prospective clinical studies have confirmed high efficacy and good tolerability of the drug in different lines of treatment of patients with NET G1 and G2. Median PFS while Aranose treatment in a single mode or in combination with capecitabine, doxorubicin and temozolomide did not differ significantly (15.3 vs 15.8, 15.3 and 17.9 months, respectively, p = 0.791). After updating the histological classification and highlighting the prognostically unfavorable subgroup of NET G3, a prospective single-center clinical study of Aranose in the first line of NET G3 therapy was conducted. The standard dosage regimen of the drug was used: 500 mg/m2 from the first to the third days, a cycle of 21 days. On average, patients received nine courses of Aranose chemotherapy, but in case of an increase in the radiological response treatment continued until disease progression or unacceptable toxicity. Median PFS in the Aranose group was 12 months, in the group of patients receiving capecitabine and oxaliplatin combination – 5 months, in capecitabine and temozolomide combination – 7 months, in the etoposide with cisplatin or carboplatin group only 4 months. The frequency of objective responses in the Aranose group was 37 % (10/27), no complete responses were recorded. Disease stabilization was achieved in 40.7 % (11/27), thus, the frequency of disease control was 77.7 % (21/27). Disease control was maintained after 6 months or more in 63 % of patients.
Presence of Elevated Interleukin – 6 (IL-6) in the Blood of COVID-19 Convalescent Patients (40 – 93 Days) Post Onset of Symptoms Could be an Indicator of Ongoing Activation of the Immune System
Authors: Bolodeoku J , Anyaeche C , Bass M , Kim TK
Published: October 2023

IL-6 concentrations rise with the onset of COVID-19 infection and is detected in 68% of patients on admission but is expected to reduce after the acute phase. IL-6 concentrations at time points: (2-7 days), (6-11 days), (11-15 days) and (13-20 days) after intensive care unit (ICU) admission showed the highest level of IL-6 concentrations at time point 2-7 days, we decided to characterize IL-6 concentrations in serum samples collected in the sera of COVID-19 convalescent patients (40 – 93 days) post onset of symptoms. The estimated IL- 6 concentrations detected ranged between 2.65 pg/ml and 29.01 pg/ml, with a median of 9.18 pg/ml. Nine out of the 28 (32.14%) patients had normal IL-6 levels (<7 pg/ml) and 19 of the 28 patients (68%) had IL-6 elevated concentrations (>7 pg/ml). The IL-6 concentrations were grouped normal (<7 pg.ml, n= 9), mildly elevated (7 – 10 pg/ml, n = 10) and elevated (>10 pg/ml n = 9). There was no relationship between IL-6 concentrations with gender, days from onset of symptoms, days from subsiding symptoms and COVID-19 IgG antibodies. There was some relationship with age, as the younger patient cohort produced much higher IL-6 concentrations than the older patient cohort. This study describes an increase in blood IL-6 concentrations in the sera of COVID-19 convalescent patients (40 – 93 days) post onset of symptoms like that seen in COVID patients on admission and higher levels seen in the younger patient cohort indicating that “cytokine storms” still occur in the recovery phase.
DIS3L2: Unveiling a New Player in Tumorigenesis, with a Key Role in Colorectal Cancer
Authors: García-Moreno Juan F. , Matos Paulo , Romão Luísa
Published: October 2023

DIS3L2 is a 3’-5’ exoribonuclease that recognizes and degrades uridylated transcripts in an exosome-independent manner and participates in several RNA degradation pathways, such as the nonsense-mediated mRNA decay, or the surveillance of aberrant structured non-coding RNAs. Although some studies have linked DIS3L2 to tumorigenesis and cancer-related processes, its exact role in the development and progression of cancer has remained unclear since the discovery of DIS3L2's ribonuclease activity a decade ago. While some authors have reported evidence of a tumor suppressor role for this exoribonuclease, other studies have shown DIS3L2 as a driver of tumorigenesis. Although differences in tissue type and methodologic approaches may somewhat account for the opposing findings, a recent study from our group further supports a pro-tumorigenic role for DIS3L2, this time in promoting colorectal cancer (CRC) progression. Indeed, proper DIS3L2 expression was proven essential to maintain key tumorigenic properties in CRC cells, including cell proliferation and invasion. Here, we summarize the current state of knowledge regarding the impact of DIS3L2 in cancer, namely in colorectal cancer. The collected data unveils DIS3L2 as a novel putative therapeutic target in cancer that warrants further investigation.
El Libro Secreto de Hermilio Valdizán: Documentos peruanos referentes a la enfermedad de Carrión
Authors: Salinas-Flores David
Published: October 2023

Hermilio Valdizán, es considerado el padre de la historiografía médica peruana, él tenía el deseo de escribir una “Enciclopedia” de la verruga peruana. Recientes revistas médicas reproducen la queja de Valdizán de no recibir apoyo del gobierno en la publicación de un libro de referencia de la enfermedad de Carrión que reúna todas las investigaciones de la enfermedad de Carrión. sin embargo, el libro soñado por Hermilio Valdizán se llegó a editar. El libro titulado “Documentos peruanos referentes a la enfermedad de Carrión” fue editado por el propio Hermilio Valdizán y Celso Bambaren, reúne las biografías de los principales investigadores de verruga peruana y sus investigaciones desde Salazar hasta mediados del siglo XX(1), “La Enciclopedia” de la verruga peruana de Valdizán prácticamente es desconocida para la mayoría de investigadores de la enfermedad de Carrión, debería ser considerado como un hito en la investigación de la enfermedad de Carrión, dado que reúne las primeras investigaciones sobre la verruga peruana y debería ser conocido y considerado como lo son, el libro de “La enfermedad de Carrión” de Ernesto Odriozola o el de “Verruga Peruana” de Raúl Rebagliati.
Impacto social y territorial por inundaciones
Authors: Zilbert Linda
Published: October 2023

La actividad humana está creando riesgos mayores y más peligrosos, y empujando al planeta hacia los límites existenciales y del ecosistema(2). Según el Informe de Evaluación Global sobre la Reducción del Riesgo de Desastre GAR 2022, los desastres reportados por año aumentaron de manera significativa en las últimas dos décadas.
Safety risks and ethical governance of biomedical applications of synthetic biology
Authors: Ou Yakun , Guo Shengjia
Published: October 2023

Background: In recent years, biomedicine has witnessed rapid advancements in applying synthetic biology. While these advancements have brought numerous benefits to patients, they have also given rise to a series of safety concerns.

Methods: This article provides a succinct overview of the current research on synthetic biology’s application in biomedicine and systematically analyzes the safety risks associated with this field. Based on this analysis, the article proposes fundamental principles for addressing these issues and presents practical recommendations for ethical governance.

Results: This article contends that the primary safety risks associated with the application of synthetic biology in biomedicine include participant safety, biosafety risks, and biosecurity risks. In order to effectively address these risks, it is essential to adhere to the principles of human-centeredness, non-maleficence, sustainability, and reasonable risk control. Guided by these fundamental principles and taking into account China’s specific circumstances, this article presents practical recommendations for ethical governance, which include strengthening ethical review, promoting the development and implementation of relevant policies, improving legal safeguards through top-level design, and enhancing technical capabilities for biocontainment.

Conclusion: As an emerging field of scientific technology, synthetic biology presents numerous safety risks and challenges in its application within biomedicine. In order to address these risks and challenges, it is imperative that appropriate measures be implemented. From a Chinese perspective, the solutions we propose serve not only to advance the domestic development of synthetic biology but also to contribute to its global progress.
Exploring key genes associated with neutrophil function and neutrophil extracellular traps in heart failure: a comprehensive analysis of single-cell and bulk sequencing data
Authors: Li Xudong , Xu Changhao , Li Qiaoqiao , Shen Qingxiang , Zeng Long
Published: October 2023

Background: Heart failure (HF) is a complex and heterogeneous manifestation of multiple cardiovascular diseases that usually occurs in the advanced stages of disease progression. The role of neutrophil extracellular traps (NETs) in the pathogenesis of HF remains to be explored.

Methods: Bioinformatics analysis was employed to investigate general and single-cell transcriptome sequencing data downloaded from the GEO datasets. Differentially expressed genes (DEGs) associated with NETs in HF patients and healthy controls were identified using transcriptome sequencing datasets and were subsequently subjected to functional enrichment analysis. To identify potential diagnostic biomarkers, the random forest algorithm (RF) and the least absolute shrinkage and selection operator (LASSO) were applied, followed by the construction of receiver operating characteristic (ROC) curves to assess accuracy. Additionally, single-cell transcriptome sequencing data analysis identified key immune cell subpopulations in TAC (transverse aortic constriction) mice potentially involved in NETs regulation. Cell-cell communication analysis and trajectory analysis was then performed on these key cell subpopulations.

Results: We identified thirteen differentially expressed genes (DEGs) associated with NET through differential analysis of transcriptome sequencing data from HF (heart failure) samples. Utilizing the Random Forest and Lasso algorithms, along with experimental validation, we successfully pinpointed four diagnostic markers (CXCR2, FCGR3B, VNN3, and FPR2) capable of predicting HF risk. Furthermore, our analysis of intercellular communication, leveraging single-cell sequencing data, highlighted macrophages and T cells as the immune cell subpopulations with the closest interactions with neutrophils. Pseudo-trajectory analysis sheds light on the differentiation states of distinct neutrophil subpopulations.

Conclusion: In this study, we conducted an in-depth investigation into the functions of neutrophil subpopulations that infiltrate cardiac tissue in TAC mice. Additionally, we identified four biomarkers (CXCR2, FCGR3B, VNN3, and FPR2) associated with NETs in HF. Our findings enhance the understanding of immunology in HF.
Development of an acute ovine model of polycystic ovaries to assess the effect of ovarian denervation
Authors: Duncan W. Colin , Nicol Linda M. , O’Hare Rosie , Witherington Jason , Miranda Jason A. , Campbell Bruce K. , Thomas Jennifer L. , Rae Michael T.
Published: October 2023

Introduction

Polycystic ovary syndrome (PCOS) seems to be associated with increased ovarian sympathetic nerve activity and in rodent models of PCOS reducing the sympathetic drive to the ovary, through denervation or neuromodulation, improves ovulation rate. We hypothesised that sympathetic nerves work with gonadotropins to promote development and survival of small antral follicles to develop a polycystic ovary phenotype.

Methods

Using a clinically realistic ovine model we showed a rich sympathetic innervation to the normal ovary and reinnervation after ovarian transplantation. Using needlepoint diathermy to the nerve plexus in the ovarian vascular pedicle we were able to denervate the ovary resulting in reduced intraovarian noradrenaline and tyrosine hydroxylase immunostained sympathetic nerves. We developed an acute polycystic ovary (PCO) model using gonadotrophin releasing hormone (GnRH) agonist followed infusion of follicle stimulating hormone (FSH) with increased pulsatile luteinising hormone (LH). This resulted in increased numbers of smaller antral follicles in the ovary when compared to FSH infusion suggesting a polycystic ovary.

Results

Denervation had no effect of the survival or numbers of follicles in the acute PCO model and did not impact on ovulation, follicular and luteal hormone profiles in a normal cycle.

Discussion

Although the ovary is richly inervated we did not find evidence for a role of sympathetic nerves in ovarian function or small follicle growth and survival.
A promising approach to monitor microplastic masses in composts
Authors: Wiesner Yosri , Bednarz Marius , Braun Ulrike , Bannick Claus Gerhard , Ricking Mathias , Altmann Korinna
Published: October 2023

Inputs of plastic impurities into the environment via the application of fertilizers are regulated in Germany and the EU by means of ordinances. Robust and fast analytical methods are the basis of legal regulations. Currently, only macro- and large microplastic contents (>1 mm) are measured. Microplastics (1–1,000 µm), are not yet monitored. Thermal analytical methods are suitable for this purpose, which can determine the mass content and can also be operated fully automatically in routine mode. Thermal extraction desorption-gas chromatography/mass spectrometry (TED-GC/MS) allows the identification of polymers and the determination of mass contents in solid samples from natural environments. In accordance with the German or European Commission (EC) Fertiliser Ordinance, composting plants should be monitored for microplastic particles with this method in the future. In this context a compost plant was sampled. At the end of the rotting process, the compost was sieved and separated in a coarse (>1 mm) and a fine fraction (<1 mm). The fine fraction was processed using density separation comparing NaCl and NaI as possible salt alternative and screened for microplastic masses by TED-GC/MS with additional validation and quality assurance experiments. With TED-GC/MS total microplastics mass contents of 1.1–3.0 μg/mg in finished compost could be detected with polyethylene mainly. What differs much to the total mass of plastics in the coarse fraction with up to 60 μg/mg, which were visually searched, identified via ATR-FTIR and gravimetrically weighted.
Dexamethasone impairs the expression of antimicrobial mediators in lipopolysaccharide-activated primary macrophages by inhibiting both expression and function of interferon β
Authors: O’Neil John D. , Bolimowska Oliwia O. , Clayton Sally A. , Tang Tina , Daley Kalbinder K. , Lara-Reyna Samuel , Warner Jordan , Martin Claire S. , Mahida Rahul Y. , Hardy Rowan S. , Arthur J. Simon C. , Clark Andrew R.
Published: October 2023

Glucocorticoids potently inhibit expression of many inflammatory mediators, and have been widely used to treat both acute and chronic inflammatory diseases for more than seventy years. However, they can have several unwanted effects, amongst which immunosuppression is one of the most common. Here we used microarrays and proteomic approaches to characterise the effect of dexamethasone (a synthetic glucocorticoid) on the responses of primary mouse macrophages to a potent pro-inflammatory agonist, lipopolysaccharide (LPS). Gene ontology analysis revealed that dexamethasone strongly impaired the lipopolysaccharide-induced antimicrobial response, which is thought to be driven by an autocrine feedback loop involving the type I interferon IFNβ. Indeed, dexamethasone strongly and dose-dependently inhibited the expression of IFNβ by LPS-activated macrophages. Unbiased proteomic data also revealed an inhibitory effect of dexamethasone on the IFNβ-dependent program of gene expression, with strong down-regulation of several interferon-induced antimicrobial factors. Surprisingly, dexamethasone also inhibited the expression of several antimicrobial genes in response to direct stimulation of macrophages with IFNβ. We tested a number of hypotheses based on previous publications, but found that no single mechanism could account for more than a small fraction of the broad suppressive impact of dexamethasone on macrophage type I interferon signaling, underlining the complexity of this pathway. Preliminary experiments indicated that dexamethasone exerted similar inhibitory effects on primary human monocyte-derived or alveolar macrophages.
Improving vasculoprotective effects of MSCs in coronary microvessels – benefits of 3D culture, sub-populations and heparin
Authors: Bumroongthai Kobkaew , Kavanagh Dean P. J. , Genever Paul , Kalia Neena
Published: October 2023

Introduction

Opening occluded coronary arteries in patients with myocardial infarction (MI) damages the delicate coronary microvessels through a process called myocardial ischaemia-reperfusion injury. Although mesenchymal stromal cells (MSCs) have the potential to limit this injury, clinical success remains limited. This may be due to (i) poor MSC homing to the heart (ii) infused MSCs, even if derived from the same site, being a heterogeneous population with varying therapeutic efficacy and (iii) conventional 2D culture of MSCs decreasing their homing and beneficial properties. This study investigated whether 3D culture of two distinctly different bone marrow (BM)-derived MSC sub-populations could improve their homing and coronary vasculoprotective efficacy.

Methods

Intravital imaging of the anaesthetised mouse beating heart was used to investigate the trafficking and microvascular protective effects of two clonally-derived BM-derived MSC lines, namely CD317neg MSCs-Y201 and CD317pos MSCs-Y202, cultured using conventional monolayer and 3D hanging drop methods.

Results

3D culture consistently improved the adhesive behaviour of MSCs-Y201 to various substrates in vitro. However, it was their differential ability to reduce neutrophil events within the coronary capillaries and improve ventricular perfusion in vivo that was most remarkable. Moreover, dual therapy combined with heparin further improved the vasculoprotection afforded by 3D cultured MSCs-Y201 by also modifying platelet as well as neutrophil recruitment, which subsequently led to the greatest salvage of viable myocardium. Therapeutic benefit could mechanistically be explained by reductions in coronary endothelial oxidative stress and intercellular adhesion molecule-1 (ICAM-1)/vascular cell adhesion molecule-1 (VCAM-1) expression. However, since this was noted by both 2D and 3D cultured MSCs-Y201, therapeutic benefit is likely explained by the fact that 3D cultured MSCs-Y201 were the most potent sub-population at reducing serum levels of several pro-inflammatory cytokines.

Conclusion

This novel study highlights the importance of not only 3D culture, but also of a specific CD317neg MSC sub-population, as being critical to realising their full coronary vasculoprotective potential in the injured heart. Since the smallest coronary blood vessels are increasingly recognised as a primary target of reperfusion injury, therapeutic interventions must be able to protect these delicate structures from inflammatory cells and maintain perfusion in the heart. We propose that relatively feasible technical modifications in a specific BM-derived MSC sub-population could achieve this.
Occupational exposure to pesticides dysregulates systemic Th1/Th2/Th17 cytokines and correlates with poor clinical outcomes in breast cancer patients
Authors: Santos Stephany Bonin Godinho dos , da Silva Janaína Carla , Jaques Hellen dos Santos , Dalla Vecchia Marina Ferronato , Ferreira Mariane Okamoto , Rech Daniel , Sierota da Silva Matheus Ryan Noah , Santos Roberta Bonin Godinho dos , Panis Carolina , Benvegnú Dalila Moter
Published: October 2023

Pesticides are compounds known to cause immunetoxicity in exposed individuals, which have a potential to substantially modify the prognosis of pathologies dependent on an efficient immune response, such as breast cancer. In this context, we examined the circulating cytokine profile of Th1/Th2/Th17 patterns in women occupationally exposed to pesticides and their correlation with worse prognostic outcomes. Peripheral blood samples were collected from 187 rural working women with breast cancer, occupationally exposed or not to pesticides, to quantify the levels of cytokines IL-1β, IL-12, IL-4, IL-17-A, and TNF -α. Data on the disease profile and clinical outcomes were collected through medical follow-up. IL-12 was reduced in exposed women with tumors larger than 2 cm and in those with lymph node metastases. Significantly reduced levels of IL-17A were observed in exposed patients with Luminal B subtype tumors, with high ki67 proliferation rates, high histological grade, and positive for the progesterone receptor. Reduced IL-4 was also seen in exposed women with lymph node invasion. Our data show that occupational exposure to pesticides induces significant changes in the levels of cytokines necessary for tumor control and correlates with poor prognosis clinical outcomes in breast cancer.
Evaluating distinct KRAS subtypes as potential biomarkers for immune checkpoint inhibitor efficacy in lung adenocarcinoma
Authors: Wang Qi , Tang Zhuoran , Li Chunyu , Li Xuefei , Su Chunxia
Published: October 2023

Background

Despite the acknowledged predictive value of KRAS in immune checkpoint inhibitor (ICI) responses, the heterogeneous behavior of its mutations in this sphere remains largely unexplored. As of now, no studies have definitively categorized KRAS subtype variations as independent prognostic indicators for ICI responses in lung cancer patients.

Methods

We analyzed a cohort of 103 patients, all harboring different KRAS mutation subtypes, and complemented this data with information from TCGA and GEO databases. Our research focused on delineating the relationships between KRAS mutation subtypes and factors like immunotherapy markers and immune cell composition, in addition to examining survival rates, drug sensitivity, and PD-L1 responses corresponding to distinct KRAS subtypes.

Results

We found that the G12V and G12D subtypes demonstrated elevated expressions of immunotherapy markers, implying a potentially enhanced benefit from immunotherapy. Significant variations were identified in the distribution of naive B cells, activated CD4+ memory T cells, and regulatory T cells (Tregs) across different KRAS mutant subtypes. A notable difference was observed in the Tumor Mutation Burden (TMB) levels across the four KRAS subtypes, with the G12D subtype displaying the lowest TMB level. Furthermore, G12C subtype showcased the worst prognosis in terms of progression-free intervals (PFI), in stark contrast to the more favorable outcomes associated with the G12A subtype.

Conclusion

Our study reveals that KRAS mutations exhibit considerable variability in predicting outcomes for LUAD patients undergoing ICI treatment. Thus, the evaluation of KRAS as a biomarker for ICIs necessitates recognizing the potential diversity inherent in KRAS mutations.
Nanomaterial payload delivery to central nervous system glia for neural protection and repair
Authors: Saksena Jayant , Hamilton Adelle E. , Gilbert Ryan J. , Zuidema Jonathan M.
Published: October 2023

Central nervous system (CNS) glia, including astrocytes, microglia, and oligodendrocytes, play prominent roles in traumatic injury and degenerative disorders. Due to their importance, active pharmaceutical ingredients (APIs) are being developed to modulate CNS glia in order to improve outcomes in traumatic injury and disease. While many of these APIs show promise in vitro, the majority of APIs that are systemically delivered show little penetration through the blood–brain barrier (BBB) or blood-spinal cord barrier (BSCB) and into the CNS, rendering them ineffective. Novel nanomaterials are being developed to deliver APIs into the CNS to modulate glial responses and improve outcomes in injury and disease. Nanomaterials are attractive options as therapies for central nervous system protection and repair in degenerative disorders and traumatic injury due to their intrinsic capabilities in API delivery. Nanomaterials can improve API accumulation in the CNS by increasing permeation through the BBB of systemically delivered APIs, extending the timeline of API release, and interacting biophysically with CNS cell populations due to their mechanical properties and nanoscale architectures. In this review, we present the recent advances in the fields of both locally implanted nanomaterials and systemically administered nanoparticles developed for the delivery of APIs to the CNS that modulate glial activity as a strategy to improve outcomes in traumatic injury and disease. We identify current research gaps and discuss potential developments in the field that will continue to translate the use of glia-targeting nanomaterials to the clinic.
Sound category habituation requires task-relevant attention
Authors: Moskowitz Howard S. , Sussman Elyse S.
Published: October 2023

Introduction

Processing the wealth of sensory information from the surrounding environment is a vital human function with the potential to develop learning, advance social interactions, and promote safety and well-being.

Methods

To elucidate underlying processes governing these activities we measured neurophysiological responses to patterned stimulus sequences during a sound categorization task to evaluate attention effects on implicit learning, sound categorization, and speech perception. Using a unique experimental design, we uncoupled conceptual categorical effects from stimulus-specific effects by presenting categorical stimulus tokens that did not physically repeat.

Results

We found effects of implicit learning, categorical habituation, and a speech perception bias when the sounds were attended, and the listeners performed a categorization task (task-relevant). In contrast, there was no evidence of a speech perception bias, implicit learning of the structured sound sequence, or repetition suppression to repeated within-category sounds (no categorical habituation) when participants passively listened to the sounds and watched a silent closed-captioned video (task-irrelevant). No indication of category perception was demonstrated in the scalp-recorded brain components when participants were watching a movie and had no task with the sounds.

Discussion

These results demonstrate that attention is required to maintain category identification and expectations induced by a structured sequence when the conceptual information must be extracted from stimuli that are acoustically distinct. Taken together, these striking attention effects support the theoretical view that top-down control is required to initiate expectations for higher level cognitive processing.
Allogenic umbilical cord tissue for temporomandibular joint injuries
Authors: Aratikatla Adarsh , Ghandour Samir , Maffulli Nicola , Gupta Manu , Gupta Ashim
Published: October 2023

The temporomandibular joint (TMJ) is crucial for functions of daily living such as mastication and articulation. Common TMJ issues include osteoarthritis, internal derangement, and myofascial pain dysfunction. Conservative methods such as physical therapy and medications are used, with surgical options such as arthroscopy and replacement for severe cases. Emerging regenerative medicine explores non-surgical treatments using human stem cells from umbilical cord derivatives, showing potential for tissue regeneration in TMJ disorders. A systematic search was conducted across PubMed, Embase, Scopus, and Web of Science databases, adhering to PRISMA guidelines, aiming to identify relevant articles published in English until August 2023. The search used specific terms to target in vitro, preclinical, and clinical studies on umbilical cord (UC)-derived tissue and mesenchymal stem cells (MSCs) for treating TMJ disorders. The search was extended to three clinical trial registries for on-going investigations related to UC tissue and MSCs for TMJ disorder management. The studies included in this article report the safety and efficacy profiles of allogenically acquired, umbilical cord-derived tissues and associated mesenchymal stem cells for temporomandibular joint ailments, future adequately powered, randomized controlled trials are warranted to conclusively justify the clinical use of this biologic therapy.
The factorial survey as an approach to investigate clinical decision-making: examining influences on a clinician's decision to initiate life-sustaining clinical technology for a child with spinal muscular atrophy type 1
Authors: Quirke Mary Brigid , Cassidy Lorna , Alexander Denise , Walsh Cathal , Hill Katie , Masterson Kate , Flynn Nia , Brenner Maria
Published: October 2023

Background

Spinal Muscular Atrophy (SMA) type 1 is a debilitating condition with a poor prognosis, though therapeutic advances are promising. Long-term ventilation is a common management strategy as respiratory function deteriorates. Without consensus on best practice respiratory management, the decision to initiate invasive LTV (I-LTV) for this group of young children involves many ethical considerations. Understanding the main influencing factors on a clinician's likelihood to initiative I-LTV for a child with chronic critical illness is important to maintain transparency and trust with the family during this challenging time.

Methods

A factorial survey was used to identify the factors that influence a clinician to support initiation of I-LTV for children with SMA type 1. Factorial survey content was based on literature and evidence-based practice and the content was subject to extensive pretesting and pilot testing. An anonymous survey was disseminated (Oct 2021–Jan 2022), via eight international professional organisations, to clinicians with experience caring for children at the time of initiation of I-LTV.

Results

251 participants answered 514 vignettes on SMA type 1. The greatest influencing factor on clinician's likelihood to initiate I-LTV was parental agreement with the need to initiate I-LTV. Additional qualitative comments from participants support this finding. Clinicians also highlighted the important role of innovative therapies as well as the availability of supports for families when considering initiation however these findings were context based.

Conclusions

The factorial survey approach provides a valuable way of identifying influencers on decision-making in sensitive situations. The findings demonstrate the acceptance of the centrality of parental influence in decisions on care delivery. Effective communication with the child's family is key to ensuring shared understanding and agreement of goals of care. More international research is needed on the long-term effects of novel treatments, as well as impact on quality of life and influence of geographical location, to inform decision-making.
The brain protection of MLKL inhibitor necrosulfonamide against focal ischemia/reperfusion injury associating with blocking the nucleus and nuclear envelope translocation of MLKL and RIP3K
Authors: Zhou Xian-Yong , Lin Bo , Chen Wei , Cao Rui-Qi , Guo Yi , Said Ali , Khan Taous , Zhang Hui-Ling , Zhu Yong-Ming
Published: October 2023

Mixed lineage kinase like protein (MLKL) is a key mediator of necroptosis. While previous studies highlighted the important role of MLKL as one of the central regulators of brain damage against acute ischemic neuronal injury, how the activation of MLKL mediates brain injuries and cell death remains unclear, especially in astrocytes. In a transient middle cerebral artery occlusion (tMCAO) rat model in vivo, and an oxygen-glucose deprivation and reoxygenation (OGD/Re) injury model in both primary cultured astrocytes and human astrocytes, we show that necrosulfonamide (NSA), a MLKL specific inhibitor, reduces infarction volume and improves neurological deficits in tMCAO-treated rats. In addition, NSA treatment, as well as RIP1K inhibitor Nec-1 or RIP3K inhibitor GSK-872 treatment, decreases the OGD/Re-induced leakage of LDH in both primary cultured astrocytes and human astrocytes. NSA treatment also reduces the number of propidium iodide (PI)-positive cells, and prevents the upregulation of necroptotic biomarkers such as MLKL/p-MLKL, RIP3K/p-RIP3K, and RIP1K/p-RIP1K in ischemic penumbra of cerebral cortex in tMCAO-treated rats or in OGD/Re-treated human astrocytes. Importantly, NSA treatment blocks both the nucleus and nuclear envelope localization of MLKL/p-MLKL and RIP3K/p-RIP3K in ischemic cerebral cortex induced by tMCAO. Similarly, Co-immunoprecipitation assay shows that NSA treatment decreases tMCAO- or OGD/Re- induced increased combination of MLKL and RIP3K in nuclear envelope of ischemic penumbra of cerebral cortex or of primary cultured astrocytes, respectively. RIP3K inhibitor GSK-872 also reduces tMCAO-induced increased combination of MLKL and RIP3K in nuclear envelope of ischemic penumbra of cerebral cortex. These data suggest NSA exerts protective effects against focal ischemia/reperfusion injury via inhibiting astrocytic necroptosis through preventing the upregulation of necroptotic kinases as well as blocking both the nucleus and nuclear envelope co-localization of p-MLKL and p-RIP3K. The translocation of p-MLKL, along with p-RIP3K, to the nuclear envelope and the nucleus may play a crucial role in MLKL-mediated necroptosis under ischemic conditions.
Diurnal decline in photosynthesis and stomatal conductance in several tropical species
Authors: Suwannarut Wachira , Vialet-Chabrand Silvere , Kaiser Elias
Published: October 2023

Photosynthesis (A) and stomatal conductance (gs) change diurnally due to internal signals, but the effects of diurnal rhythms on dynamic photosynthetic behavior are understudied. We examined diurnal changes in A and gs in ten tropical species: across species, there was a tendency for A and gs to decline diurnally when these were repeatedly measured under either steady-state or fluctuating irradiance conditions. We then examined in more detail the irradiance-induced kinetics of gas exchange in a C3 and C4 crop species each, namely fig (Ficus carica) and sugarcane (Saccharum officinarum). During the day, fig showed significantly slower photosynthetic induction and lower gs, as well as a slower gs increase, in the afternoon than in the morning and noon. Sugarcane showed a reduction in steady-state A reached under high irradiance and slower gs increase as well as lower gs reached under high irradiance, but no changes in the rate of photosynthetic induction, in the afternoon, compared to morning and noon. These reductions in the afternoon were not reverted by a dark treatment in the middle of the day, suggesting that the decrease was not proportional to diurnal time-integrated carbon fixation. Repeated exposure to light- and shadeflecks (1000 and 50 μmol m-2 s-1, lasting 20 min each) revealed fundamental differences in stomatal regulation between species: in fig, stomata opened and closed slowly, and their opening became progressively slower under a series of lightflecks, whereas sugarcane showed much faster stomatal opening than closure that was unchanged during the course of the day. Our results highlight that steady-state rates and irradiance-induced kinetics of photosynthesis and stomatal movement change diurnally in most species studied, and that they do so differently in fig and sugarcane.
Understanding the prolonged impact of online sexual abuse occurring in childhood
Authors: Schmidt Felipa , Varese Filippo , Bucci Sandra
Published: October 2023

Introduction

There has been a rapid increase in prevalence rates of online sexual abuse (OSA). Existing research has highlighted the negative impact OSA can have on victims. However, there is a gap in understanding the long-term impact of OSA when it occurred in childhood.

Methods

This qualitative study comprised interviews with eight female participants aged 18–28  years recruited in UK NHS Trusts, and via mental health charities, University bulletins and social media. Each participant self-reported having experienced abuse through either the production or dissemination of sexual material online.

Results

Results showed that the longer-term impact of OSA was multi-fold, including negative impact on sense of self and broader interpersonal relationships, and significant impact on the participants’ mental health, including experiences of self-harm, anxiety, and low mood. Likewise, participants discussed long-term apprehension to taking images and the added fear and worry that their sexual images were distributed online. Seven participants had received mental health support but only two recounted a positive experience when receiving support for OSA.

Discussion

Future research using a quantitative longitudinal design is needed to further explore the prolonged impact of OSA. Clinical implications of the research highlight the need for support services to assess the impact of OSA and interventions that target OSA experiences.
Understanding the reparative effects of schema modes: an in-depth analysis of the healthy adult mode
Authors: Yakın Duygu , Arntz Arnoud
Published: October 2023

Objectives

Evidence in favor of schema therapy's effectiveness in treating personality disorders is growing. One of the central and recently popular concepts of schema therapy is schema modes [i.e., temporary emotional–cognitive–behavioral states resulting from the activation of early maladaptive schemas (EMSs)]. A key aspect herein is self-reparenting, i.e., a healing relationship between the healthy adult (HA, i.e., compassionate and healthy emotional states, and functional dealing with reality) and the child modes (i.e., representation of fragile and hurt feelings and dysfunctional coping). Through an in-depth qualitative analysis, we aimed to better understand the components of the HA that enable self-reparenting.

Method

Purposive sampling procedures were used to recruit eligible participants (n = 10) with relatively strong HA modes, as determined by high scores on positive affect and satisfaction with life measures and low scores on EMSs and psychopathological symptom measures. Semi-structured 45- to 60-min face-to-face interviews were conducted individually, in which individuals were asked to help the child modes reflected in the pictures. Interviews were then analyzed using deductive thematic analysis in MaxQDA.

Results and discussion

The analysis revealed three superordinate themes comprising of a total of 10 group themes: (1) bonding between HA and the vulnerable child modes (“Bond”); (2) balancing expression and inhibition of adult and child mode emotions (“Balancing”); and (3) opposing demanding and critical voices and maladaptive coping styles (“Battle”). Furthermore, a strong HA mode seems to have a reciprocal relationship with the child modes: the HA gives nurturance and protection to the child modes, and the child modes boost up the HA with spontaneity and happiness. In conclusion, emotional stability and resilience may be highest when HA-child mode interaction happens bidirectionally; when the child modes get reparented by the HA, and the HA is informed by the child modes.
Maternal factors associated with early childhood caries among 3–5-year-old children with low socio-economic status in Trishal, Bangladesh
Authors: Haque Farzana , Folayan Morenike Oluwatoyin , Virtanen Jorma Ilmari
Published: October 2023

Introduction

Early Childhood Caries (ECC) is more prevalent in nations where a larger portion of the population resides below the poverty line. This study aimed to evaluate the connections between maternal awareness, attitudes, practices related to oral health, and the occurrence of ECC among children aged 3–5 years in Bangladesh, a low–middle income country with high level of poverty.

Methods

This cross–sectional study recruited mother–child pairs with a focus on children aged 3–5 years from low socioeconomic backgrounds in Trishal, Bangladesh. Data collected included maternal oral health knowledge, attitudes, and behaviors. Clinical examinations were conducted to check for dental plaque on the upper central incisors' labial surfaces. ECC was identified using the ICDAS II index criteria. Associations between maternal oral health knowledge, attitudes, behaviors, and children's plaque score and caries status were analyzed using multivariable logistic regression, and adjusting for confounding variables (child's age, gender, mother's age, education, and number of children).

Results

Among 532 mother-child pairs, 491 (93.2%) mothers were unaware of the role of fluoride in preventing caries, while 516 (97%) recognized the importance of using fluoridated toothpaste during brushing. Additionally, 520 (97.7%) mothers reported not knowing how to brush their child's teeth, and 87 (16.4%) brushed their children's teeth twice daily. Visible dental plaque was observed in 420 (78.9%) children, and 321 (60.3%) had ECC. Higher plaque score increased the odds of ECC in the study population (AOR: 5.617, 95% CI: 3.511–8.987).

Conclusions

Mothers of preschool children with low socioeconomic status were poorly aware of caries preventive behaviors and had suboptimal oral health practices for their children. The plaque score was the only oral health factor that seems to increase the risk for ECC among children with low socio-economic status in Bangladesh. It is imperative to prioritize support and interventions aimed at improving oral hygiene practices to reduce ECC risk in this population.
A comparative study of canine epididymal sperm collection techniques and cryopreservation
Authors: Ali Hassan Hiba , Banchi Penelope , Domain Guillaume , El Khoury Rosemary , Chaaya Rana , Wydooghe Eline , Smits Katrien , Van Soom Ann
Published: October 2023

Introduction

An optimized collection method and freezing protocol for preservation of epididymal spermatozoa remains a topic of interest to many scientists. The current study focused on the collection and preservation of canine epididymal spermatozoa. During the process of collection of canine epididymal spermatozoa, blood content can occur, which may affect sperm cryopreservation in a negative way. Here, we compared first two epididymal sperm collection techniques [epididymal mincing (EM) and single incision epididymal sperm aspiration (SESA)]; and next we tried to solve the issue of blood content using an erythrocyte lysis buffer (ELB).

Methods

Hence spermatozoa were collected after weighing the epididymides, either by EM or SESA, and sperm quality assessed prior to and post freezing (concentration, total sperm output (TSO), motility, viability and morphology). Next, new sperm samples were collected from eight epididymides by EM and subjected either to a standard freezing protocol or to an ELB treatment freezing protocol. Post-thaw sperm parameters (concentration, TSO, motility, viability and morphology), including intracellular reactive oxygen species (ROS) and lipid peroxidation were assessed. The correlation between the weight of the epididymis and the TSO was evaluated based on the collection technique, and differences in sperm parameters were detected both within different collection techniques and between different pre-freezing treatment protocols.

Results

There was a very strong correlation between the weight of the epididymis and the TSO for the EM technique (p  =  0.002, R2 =  0.6), along with an increased sperm motility with EM compared to SESA (median 80%, inter-quartile range (IQR) 88–65 and median 67.5%, IQR 72.5–52.5, respectively; (p  =  0.002). Post-thaw samples subjected to ELB treatment freezing protocol had lower motility and higher intracellular ROS compared to the standard freezing protocol (motility: median 56.25%, IQR 60–48.75 and median 70%, IQR 72.5–63, respectively; p   =  0.01; ROS: median 78.5%, IQR 81.25–75.5 and median 70%, IQR 70.5–68.75, respectively; (p  =  0.04).

Discussion

The results indicated that EM is a better technique to harvest epididymal spermatozoa despite the presence of some blood content. Furthermore, the ELB treatment should not be implemented to remove those red blood cells prior to cryopreservation of epididymal spermatozoa in dogs.
Four Markers Useful for the Distinction of Intrauterine Growth Restriction in Sheep
Authors: Wang Wannian , Chen Sijia , Qiao Liying , Zhang Siying , Liu Qiaoxia , Yang Kaijie , Pan Yangyang , Liu Jianhua , Liu Wenzhong
Published: October 2023

Intrauterine growth restriction (IUGR) is a common perinatal complication in animal reproduction, with long-lasting negative effects on neonates and postnatal animals, which seriously negatively affects livestock production. In this study, we aimed to identify potential genes associated with the diagnosis of IUGR through bioinformatics analysis. Based on the 73 differentially expressed related genes obtained by differential analysis and weighted gene co-expression network analysis, we used three machine learning algorithms to identify 4 IUGR-related hub genes (IUGR-HGs), namely, ADAM9, CRYL1, NDP52, and SERPINA7, whose ROC curves showed that they are a good diagnostic target for IUGR. Next, we identified two molecular subtypes of IUGR through consensus clustering analysis and constructed a gene scoring system based on the IUGR-HGs. The results showed that the IUGR score was positively correlated with the risk of IUGR. The AUC value of IUGR scoring accuracy was 0.970. Finally, we constructed a new artificial neural network model based on the four IUGR-HGs to diagnose sheep IUGR, and its accuracy reached 0.956. In conclusion, the IUGR-HGs we identified provide new potential molecular markers and models for the diagnosis of IUGR in sheep; they can better diagnose whether sheep have IUGR. The present findings provide new perspectives on the diagnosis of IUGR.