bluuebunny/crossref_metadata_2025 huggingface dataset:
Hilal-i Ahmer Cemiyeti Viyana Hanımlar Merkezi ve Faaliyetleri
Authors: Şimşek Muttalip
Published: October 2022

Hilal-i Ahmer Cemiyeti, Birinci Dünya Savaşı esnasında müttefik ülkelerde yardım toplayabilmek ve ihtiyaç duyulan malzemeleri Avrupa’dan temin edebilmek amacıyla şubeler açmıştı. Bunlardan biri de Hanımlar Merkez-i Heyetiyesine bağlı olarak Viyana’da kurulan Hanımlar Merkeziydi (Frauenverein vom Ottomanischen Roten Halbmond in Wien). Viyana Sefiri Hüseyin Hilmi Paşa’nın eşi Fatma Zehra Hanım’ım girişimleriyle 1916 yılının sonlarına doğru açılan Hanımlar Merkezi, Galiçya Cephesi’nde yaralanan ve Avusturya-Macaristan İmparatorluğu sınırları içerisinde bulunan hastanelerde tedavi altına alınan Türk askerlerinin her türlü ihtiyacını karşılamaya çalıştığı gibi Avusturya ve Macaristan’da yürüttüğü yardım toplama çalışmalarıyla da cemiyete büyük destek sağlamıştı. Viyana ve çevresinden toplanacak yardımlar için Wiener Bankverein ve Postsparkasse gibi Viyana’nın önde gelen bankalarında birer bağış hesabı açan Hanımlar Merkezinin çalışmalarına başta Viyana Sefiri H. Hilmi Paşa olmak üzere, Sefaret Müsteşarı R. Blacque ve Hilal-i Ahmer Cemiyeti Viyana Murahhası Dr. Hikmet Bey destek olmaya çalışmışlardı.
Viyana Hanımlar Merkezinin faaliyetlerinin değerlendirileceği bu çalışmada, evvelâ Viyana’daki Türk kadınlarını böyle bir teşebbüse sevk eden etkenler ifade edilecek, daha sonra Hanımlar Merkezinin kuruluşu ve faaliyete başlamasıyla ilgili hususlar hakkında bilgi verilecektir. Ayrıca toplanan yardımlar ve Galiçya Cephesi’nde gerek Hilal-i Ahmer Viyana Murahhaslığının gerekse Hanımlar Merkezinin çalışmaları başta arşiv belgeleri olmak üzere dönemin Avusturya basını ışığında ortaya konacaktır.
THE EFFECTS OF SENSE AND INFORMATION QUALITY IN VIRTUAL TRAVEL EXPERIENCE ON VISIT INTENTION
Authors: AKDOĞAN Mehmet Şükrü , KURU Duran
Published: October 2022

The rapid spread of the COVID-19 epidemic and its transformation into a pandemic caused travel restrictions around the world and people had to stay in their homes. In this period, businesses that offer product or service that require physical contact or make it compulsory to be together with other people, especially businesses operating in the tourism sector, are among the most affected by the COVID-19 pandemic. In order to reduce these effects, many tourism businesses have started to develop virtual travel tours for their target audience to experience a destination at home. In this context, it is aimed to investigate the effects of the information quality of the virtual travel experience and the satisfaction created by the perceived sense of the virtual travel experience on the intentions of visiting that destination in the real world. The population of the research consists of individuals who have virtual travel experience. Among the individuals constituting the population, 564 people were reached by convenience sampling method, 172 people were excluded because they stated that they did not have a virtual travel experience or because they were under the age of 18, and 392 people were included in the study. In the research, factor, correlation, and regression analyzes were applied with a statistical package program to the data obtained by the online survey application. In the results of the analysis, it was found that the sense of virtual travel and the quality of information perceived from a destination experience in the virtual world have a positive and significant effect on satisfaction with virtual reality travel. It has been determined that this satisfaction, which consists of virtual reality travel, has a positive and relatively strong significant effect on visit intention.
Chemokine Pathway Can Be the Potential Therapeutic Target for Hypertrophic Scar
Authors: Umeyama Hirokatsu , Ding Jie , Tredget Edward E.
Published: October 2022

Hypertrophic scar (HTS) is a dermal form of fibroproliferative disease that develops after deep burns, skin injuries, and surgical wounds. HTS is defined as a visible, elevated scar that does not spread into surrounding tissues and often regresses. HTS often leads to physical and psychological issues for patients. Cellular and molecular agents, such as chemokines, bone marrow derived stem cells, TGF-β, fibroblast heterogeneity, toll-like receptor 4, and small leucine-rich proteoglycans, have been known to play an important role in wound healing and abnormal scar formation. Targeting these agents could have therapeutic potential for the treatment of pathological scars. HTS often causes contracture deformities, aesthetic disfigurement, and prolonged periods of hospitalisation and rehabilitation, leading to psychological complications. Numerous treatments have been described for HTS, but the optimal treatment has not yet been established. Chemokines are implicated in all stages of wound healing, but hyperactivity of these agents leads to excessive scarring. A better understanding of the mechanisms of chemokine action, such as the role of the signalling agents in wound healing and abnormal scar formation, will help to establish more effective therapeutic strategies for HTS.
Clinical Conditions that Masquerade as Urticaria
Authors: Kimchi Nofar , Bernstein Jonathan A.
Published: October 2022

Chronic urticaria is one of the most commonly diagnosed dermatoses. Following diagnosis, correct identification and proper treatment significantly reduces disease activity, thereby improving the patient’s quality of life. However, there is an extensive differential diagnosis for chronic urticaria that, if missed, can lead to life-threatening sequelae. Many of the diseases that masquerade as urticaria are rare and often have a significant delay in diagnosis. This paper aims to fill the gap in the literature by clearly characterising the cutaneous eruptions and atypical findings in many of the most common mimickers of chronic urticaria. Conditions such as erythema marginatum seen in conjunction with hereditary angioedema, urticaria vasculitis, autoinflammatory cryopyrin-associated periodic syndromes, adult-onset Still’s disease and systemic onset juvenile arthritis, Schnitzler syndrome, erythema multiforme, and cutaneous mastocytosis will be discussed.
After Conventional Wisdom Has Failed, What Drives Wound Healing?
Authors: Lincoln Vadim , Tang Xin , Chen Mei , Li Wei
Published: October 2022

Between 2006 and 2015, the U.S. Food and Drug Administration’s (FDA) overall likelihood of approval (LOA) from Phase I clinical trials for all therapeutic candidates was 9.6%, with the highest LOA in haematology (26.1%) and the lowest in oncology (5.1%). Two critical features attributed to the success of advancing trials were i) targeting driver genes responsible for disease, and ii) use of human disease-relevant animal models during preclinical studies. For decades, conventional wisdom has been that growth factors are the drivers of wound healing, but few have either advanced to clinical applications or proven effective. The purpose of this paper is to explore heat shock protein 90-alpha (Hsp90α)’s role as a potential driver of wound healing and as a possible future therapeutic entity through a review of recent literature, including studies with human disease-relevant animal models. Of the approximately 7,000 gene products generated by a given mammalian cell type, the Hsp90 family of proteins (Hsp90α and Hsp90β) accounts for 2–3% of them. Hsp90β fulfils the role of an intracellular chaperone, but Hsp90α’s intracellular function is surprisingly dispensable. Instead, the abundancy of Hsp90α appears to have been prepared for extracellular purposes. When secreted via exosomes by cells under environmental stress, such as injury, Hsp90α protects cells from hypoxia-induced cell death, reduces local inflammation, and subsequently promotes cell migration to repair the injured tissue. Unlike conventional growth factors, secreted Hsp90α stimulates all major cell types involved in wound healing equally, resists microenvironmental inhibitors like TGFβ and hyperglycaemia, and is highly stable. Inhibition of exosome-mediated Hsp90α secretion, neutralisation of Hsp90α’s ATPase-independent extracellular functions, or interruption of Hsp90α-LRP-1 signalling blocks wound closure in vivo. Topical application of Hsp90α’s therapeutic entity, F-5 (a 115-amino acid peptide), has shown great promise for healing acute burn and diabetic wounds in mice and pigs.
From Evolution to Revolution: IL-23 in the Treatment of Psoriasis Patients
Authors: Scutt Paul
Published: October 2022

This symposium, which took place during the 2018 meeting of the European Academy of Dermatology and Venereology (EADV) in Paris, France, provided an overview of the IL-23 revolution in psoriasis, with a specific focus on psoriasis pathogenesis and its relation to potential treatment targets and the development of novel targeted immune therapies. The session focussed on the discovery and development of IL-12 and IL-23-targeted therapies for psoriasis, the role of IL-23 in disease control, and the implications of recent data for clinical practice.

An increasing number of potential treatment options are becoming available for psoriasis, and the differential effect of these agents on various signalling pathways has facilitated a greater understanding of the molecular mechanisms driving disease progression. The symposium initially explored the central role of IL-23 in psoriasis, the mode of action of the monoclonal antibody (mAb) guselkumab in targeting this heterodimeric cytokine, and the parameters associated with a maintenance of response in patients with psoriasis undergoing treatment. The speakers subsequently reviewed current data relevant to the blockade of IL-23 versus dual blockade of IL-12/23, or blockade of the downstream effector IL-17, and the relative effects of these different strategies in psoriasis at the molecular and cellular levels. The concept of ‘disease memory’ in psoriasis was also explored, with an examination of recent data of patients with long-lasting remission, and disease models and future investigations discussed.
Using forensics to teach the natural sciences and raise student consciousness about gender-based social issues
Authors: de Almeida Cordeiro Jéssica , Gomes da Silva Matheus , Viana Gomes Josiele , Miranda Barata da Silva Andreza , Moraes Rolim Eberlanny , Luzia Ferreira de Souza Andrea , Fernandes de Moura do Carmo Dominique , Mendonça Cost Alan , José Sousa Maia Paulo
Published: October 2022

The way the Natural Sciences has been conventionally taught in school, i.e., by means of lecture-based methods, has been shown ineffective. For this reason, many alternative methods of teaching and learning have been proposed. This study focuses on the teaching of the Natural Sciences by the employ of ludic investigative activities in the context of forensic science. It proposes an alternative way of teaching the Natural Sciences associated with issues relevant to students and society at large. To this end, a case of femicide was used to teach topics of the Natural Sciences while addressing an important social issue, i.e., gender-based violence. This research, a case study of a qualitative nature, was carried out at Colégio de Aplicação in Macaé (CAp), RJ, Brazil. Its proposed teaching-learning activities were conducted over three consecutive 90-minute classes. The participating students answered pre- and post-intervention questionnaires on the scientific concepts addressed by the activities and the social issue in question, i.e., femicide. The students also participated in a discussion about the social issue at hand at the end of the intervention. The analysis of the collected data suggests that the teaching-learning method employed in this research is a viable way of teaching the Natural Sciences, especially Chemistry, in an interdisciplinary and contextualized fashion.
Processos de formação de professores das licenciaturas em Ciências da Natureza: uma revisão sistemática
Authors: Luana Sganzerla Francieli , Godinho Soares Renata , Menezes de Oliveira Soruco Thais , Ruppenthal Raquel
Published: October 2022

A formação de professores aos poucos tem ganhado força, com o intuito de transformações na forma de ensinar, modelos didáticos utilizados, práticas pedagógicas facilitando que a interdisciplinaridade seja inserida de maneira que aconteça a interação e interligação entre as disciplinas, para melhor compreensão dos fenômenos do cotidiano. Buscou-se mapear as estratégias e abordagens metodológicas utilizadas para a formação inicial e continuada, em licenciaturas interdisciplinares na área de Ciências da Natureza. Realizou-se uma pesquisa bibliográfica, no portal de periódicos da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), segundo os descritores: ("formação de professor*") AND ("ciências") AND ("natureza"), selecionando apenas artigos com atividades realizadas com licenciatura em Ciências da Natureza ou Licenciatura Interdisciplinar (licenciaturas em Educação do Campo), com foco na área de Ciências da Natureza. Dos achados, selecionou-se 11 artigos publicados entre os anos de 2015 a 2020, sendo os mesmos divididos em dois tópicos: Formação de professores com estratégias ativas para os trabalhos que apresentassem alguma atividade prática em que o professor mostrasse ser sujeito ativo, e Formação de professores com abordagens teórico-reflexivo, as atividades práticas eram demonstradas aos professores participantes, seguida de teoria o que torna o envolvido um sujeito passivo. Conclui-se que discutir temas interdisciplinares de forma que haja trocas de conhecimento e experiências, na formação inicial e continuada, têm importância significativa do papel do professor para a construção do conhecimento.
Rodents in agriculture and public health in Malawi: Farmers’ knowledge, attitudes, and practices
Authors: Donga Trust Kasambala , Bosma Luwieke , Gawa Nyson , Meheretu Yonas
Published: October 2022

Given that rodents are responsible for nearly 280 million cases of undernutrition worldwide and that about 400 million people are affected by rodent-associated zoonoses annually, management of rodent populations that are agricultural pests and/or reservoirs of pathogens is a major food security and public health matter. In sub-Saharan Africa, the median crop loss due to rodents is about 16% in the field and around 8% during storage. The impact on public health is not well-established, albeit over 60 zoonotic diseases can be spread to humans via rodents. Therefore, focusing on rodent-related community knowledge, attitudes, and practices is crucial to establishing robust baseline information as a springboard for future targeted studies. The study was conducted in September 2020 in Lilongwe and Nkhata Bay districts in Central and Northern Malawi, respectively. A semi-structured questionnaire, focus group discussions, and interviews with key informants were used. Farmers reported rodents were a major problem for staple crops (maize, rice, and cassava) and the main species responsible were the Natal multimammate mouse (Mastomys natalensis), silver mole-rat (Heliophobius argenteocinereus), and house mouse (Mus musculus domesticus). Awareness of rodent-associated health risks is very low, as exemplified by reports of rodent–human bites, eating rodent-contaminated food, and processing and consumption of wild rodents in poor hygienic conditions, and these practices were flourishing when Malawi was a bubonic plague endemic country. Rodent management is less practiced, and when practiced, it is symptomatic. It is considered a matter of individual households and typically relies on the use of rodenticides and insecticides without proper dosage and user instructions. We recommend rigorous campaigns to create better awareness among the public regarding the impacts of rodents on agriculture and community health and the need for community engagement for effective rodent management. A paradigm shift is needed by adapting and adopting practices of ecologically-based rodent management and reducing dependence on synthetic chemical rodenticides.
Testing Raman spectroscopy as a diagnostic approach for Lyme disease patients
Authors: Goff Nicolas K. , Dou Tianyi , Higgins Samantha , Horn Elizabeth J. , Morey Rohini , McClellan Kyle , Kurouski Dmitry , Rogovskyy Artem S.
Published: October 2022

Lyme disease (LD), the leading tick-borne disease in the Northern hemisphere, is caused by spirochetes of several genospecies of the Borreliella burgdorferi sensu lato complex. LD is a multi-systemic and highly debilitating illness that is notoriously challenging to diagnose. The main drawbacks of the two-tiered serology, the only approved diagnostic test in the United States, include poor sensitivity, background seropositivity, and cross-reactivity. Recently, Raman spectroscopy (RS) was examined for its LD diagnostic utility by our earlier proof-of-concept study. The previous investigation analyzed the blood from mice that were infected with 297 and B31 strains of Borreliella burgdorferi sensu stricto (s.s.). The selected strains represented two out of the three major clades of B. burgdorferi s.s. isolates found in the United States. The obtained results were encouraging and prompted us to further investigate the RS diagnostic capacity for LD in this study. The present investigation has analyzed blood of mice infected with European genospecies, Borreliella afzelii or Borreliella garinii, or B. burgdorferi N40, a strain of the third major class of B. burgdorferi s.s. in the United States. Moreover, 90 human serum samples that originated from LD-confirmed, LD-negative, and LD-probable human patients were also analyzed by RS. The overall results demonstrated that blood samples from Borreliella-infected mice were identified with 96% accuracy, 94% sensitivity, and 100% specificity. Furthermore, human blood samples were analyzed with 88% accuracy, 85% sensitivity, and 90% specificity. Together, the current data indicate that RS should be further explored as a potential diagnostic test for LD patients.
Effects of Hst3p inhibition in Candida albicans: a genome-wide H3K56 acetylation analysis
Authors: Conte Marisa , Eletto Daniela , Pannetta Martina , Petrone Anna M. , Monti Maria C. , Cassiano Chiara , Giurato Giorgio , Rizzo Francesca , Tessarz Peter , Petrella Antonello , Tosco Alessandra , Porta Amalia
Published: October 2022

Candida spp. represent the third most frequent worldwide cause of infection in Intensive Care Units with a mortality rate of almost 40%. The classes of antifungals currently available include azoles, polyenes, echinocandins, pyrimidine derivatives, and allylamines. However, the therapeutical options for the treatment of candidiasis are drastically reduced by the increasing antifungal resistance. The growing need for a more targeted antifungal therapy is limited by the concern of finding molecules that specifically recognize the microbial cell without damaging the host. Epigenetic writers and erasers have emerged as promising targets in different contexts, including the treatment of fungal infections. In C. albicans, Hst3p, a sirtuin that deacetylates H3K56ac, represents an attractive antifungal target as it is essential for the fungus viability and virulence. Although the relevance of such epigenetic regulator is documented for the development of new antifungal therapies, the molecular mechanism behind Hst3p-mediated epigenetic regulation remains unrevealed. Here, we provide the first genome-wide profiling of H3K56ac in C. albicans resulting in H3K56ac enriched regions associated with Candida sp. pathogenicity. Upon Hst3p inhibition, 447 regions gain H3K56ac. Importantly, these genomic areas contain genes encoding for adhesin proteins, degradative enzymes, and white-opaque switching. Moreover, our RNA-seq analysis revealed 1330 upregulated and 1081 downregulated transcripts upon Hst3p inhibition, and among them, we identified 87 genes whose transcriptional increase well correlates with the enrichment of H3K56 acetylation on their promoters, including some well-known regulators of phenotypic switching and virulence. Based on our evidence, Hst3p is an appealing target for the development of new potential antifungal drugs.
Molecular interplays of the Entamoeba histolytica endosomal sorting complexes required for transport during phagocytosis
Authors: Bañuelos Cecilia , Betanzos Abigail , Javier-Reyna Rosario , Galindo Ausencio , Orozco Esther
Published: October 2022

Entamoeba histolytica, the causative agent of human amoebiasis, exhibits a continuous membrane remodelling to exert its virulence properties. During this dynamic process, the Endosomal Sorting Complexes Required for Transport (ESCRT) machinery is a key player, particularly in phagocytosis, a virulence hallmark of this parasite. In addition to ESCRT, other molecules contribute to membrane remodelling, including the EhADH adhesin, EhRabs, actin, and the lysobisphosphatidic acid (LBPA). The endocytosis of a prey or molecules induces membrane invaginations, resulting in endosome and multivesicular bodies (MVBs) formation for cargo delivery into lysosomes. Alternatively, some proteins are recycled or secreted. Most of these pathways have been broadly characterized in other biological systems, but poorly described in protozoan parasites. Here, we encompass 10 years of ESCRT research in E. histolytica, highlighting the role of the ESCRT-I and ESCRT-III components and the EhADH and EhVps4-ATPase accessory proteins during phagocytosis. In particular, EhADH exhibits a multifunctional role along the endocytic pathway, from cargo recognition to endosome maturation and lysosomal degradation. Interestingly, the interaction of EhADH with EhVps32 seems to shape a concurrent route to the conventional one for MVBs biogenesis, that could optimize their formation. Furthermore, this adhesin is secreted, but its role in this event remains under study. Other components from the endosomal pathway, such as EhVps23 and LBPA, are also secreted. A proteomic approach performed here, using an anti-LBPA antibody, revealed that some proteins related to membrane trafficking, cellular transport, cytoskeleton dynamics, and transcriptional and translational functions are secreted and associated to LBPA. Altogether, the accumulated knowledge around the ESCRT machinery in E. histolytica, points it out as a dynamic platform facilitating the interaction of molecules participating in different cellular events. Seen as an integrated system, ESCRTs lead to a better understanding of E. histolytica phagocytosis.
Interleukin 6 receptor is not directly involved in regulation of body weight in diet-induced obesity with and without physical exercise
Authors: Minafra Anna Rita , Chadt Alexandra , Rafii Puyan , Al-Hasani Hadi , Behnke Kristina , Scheller Jürgen
Published: October 2022

High level of interleukin 6 (IL-6), released by adipocytes in an obesity-induced, low grade inflammation state, is a regulator of insulin resistance and glucose tolerance. IL-6 has also regenerative, anti-inflammatory and anti-diabetogenic functions, when secreted as myokine by skeletal muscles during physical exercise. IL-6 mainly activates cells via two different receptor constellations: classic and trans-signalling, in which IL-6 initially binds to membrane-bound receptor (IL-6R) or soluble IL-6 receptor (sIL-6R) before activating signal transducing gp130 receptor. Previously, we generated transgenic soluble IL-6 receptor +/+ (sIL-6R+/+) mice with a strategy that mimics ADAM10/17 hyperactivation, reflecting a situation in which only IL-6 trans-signalling is active, whereas classic signalling is completely abrogated. In this study, we metabolically phenotyped IL-6R deficient mice (IL-6R-KO), sIL-6R+/+ mice and wild-type littermates fed either a standard chow (SD) or a high-fat diet (HFD) in combination with a 6-weeks treadmill exercise protocol. All mice were subjected to analyses of body weight and body composition, determination of blood glucose and insulin level under fasting conditions, as well as determination of substrate preference by indirect calorimetry. Neither classic IL-6 nor trans-signalling do influence the outcome of diet-induced obesity, insulin sensitivity and glycaemic control. Furthermore, IL-6R deficiency is not impairing the beneficial effect of physical exercise. We conclude that the IL-6R does not play a requisite role in regulation of body weight and glucose metabolism in diet-induced obese mice.
New horizons of biomaterials in treatment of nerve damage in diabetes mellitus: A translational prospective review
Authors: Raghav Alok , Singh Manish , Jeong Goo-Bo , Giri Richa , Agarwal Saurabh , Kala Sanjay
Published: October 2022

Background

Peripheral nerve injury is a serious concern that leads to loss of neuronal communication that impairs the quality of life and, in adverse conditions, causes permanent disability. The limited availability of autografts with associated demerits shifts the paradigm of researchers to use biomaterials as an alternative treatment approach to recover nerve damage.

Purpose

The purpose of this study is to explore the role of biomaterials in translational treatment approaches in diabetic neuropathy.

Study design

The present study is a prospective review study.

Methods

Published literature on the role of biomaterials in therapeutics was searched for.

Results

Biomaterials can be implemented with desired characteristics to overcome the problem of nerve regeneration. Biomaterials can be further exploited in the treatment of nerve damage especially associated with PDN. These can be modified, customized, and engineered as scaffolds with the potential of mimicking the extracellular matrix of nerve tissue along with axonal regeneration. Due to their beneficial biological deeds, they can expedite tissue repair and serve as carriers of cellular and pharmacological treatments. Therefore, the emerging research area of biomaterials-mediated treatment of nerve damage provides opportunities to explore them as translational biomedical treatment approaches.

Conclusions

Pre-clinical and clinical trials in this direction are needed to establish the effective role of several biomaterials in the treatment of other human diseases.
Preoperative voice analysis and survival outcomes in papillary thyroid cancer with recurrent laryngeal nerve invasion
Authors: Chen Jiaming , Zhong Qi , Hou Lizhen , Ma Hongzhi , Shi Qian , Feng Ling , He Shizhi , Lin Yansong , Lian Meng , Shen Xixi , Wang Ru , Fang Jugao
Published: October 2022

Objective

To investigate the clinicopathological characteristics of papillary thyroid cancer (PTC) and identify risk factors for postoperative recurrence of PTC with recurrent laryngeal nerve (RLN) involvement.

Methods

In total, 171 patients (112 women and 59 men, age: 18–80 years, and 65 patients aged ≥ 55) with T4a PTC with RLN involvement, treated at Beijing Tongren Hospital, Capital Medical University, from January 2006 to December 2020, were retrospectively examined. Clinicopathological characteristics, including voice analysis results, and survival outcomes were assessed. The Mann–Whitney U and Kruskal–Wallis H tests were used to analyze differences in acoustic parameters. The Kaplan–Meier method was used to calculate the overall survival (OS) and recurrence-free (RFS) rates. Univariate and multivariate Cox regression analyses were performed of the clinical data.

Results

The postoperative follow-up period ranged from 12 to 196 months (mean: 66.18 months). Of the 171 patients, 16 had recurrence and 8 died of thyroid-related diseases. The 5-year OS rate was 95.22%. The 5-year RFS rate was 89.38%. Jitter and shimmer were higher and maximum phonation time was shorter in patients with preoperative vocal cord paralysis (VCP) than in those without RLN involvement, and in those with RLN involvement but without preoperative VCP. Acoustic parameters were similar in patients with no preoperative VCP and those without RLN involvement. Voice analysis results did not differ between cases with RLN adhesion and RLN invasion. Univariate analysis showed that age at onset ≥ 55 years, preoperative RLN palsy, and esophageal invasion were risk factors for postoperative recurrence of PTC with RLN involvement. Multivariate analysis showed that onset age ≥ 55 years (OR 4.52, 95% confidence interval: 1.44–14.19, P = 0.010) was an independent risk factor for recurrence.

Conclusions

PTC patients with RLN invasion can achieve good outcomes. Preoperative voice analysis may offer insights into RLN function. Age of onset ≥ 55 years is an independent risk factor for postoperative recurrence in T4a PTC patients.
Anti-obesity pharmacotherapy for treatment of pediatric type 2 diabetes: Review of the literature and lessons learned from adults
Authors: Bensignor Megan O. , Kelly Aaron S. , Arslanian Silva
Published: October 2022

Type 2 diabetes mellitus (T2DM) in adolescents is a more rapidly progressive disease, associated with earlier and higher rates of microvascular complications than in adults. As obesity is a significant risk factor for T2DM development and progression, the American Diabetes Association (ADA) recommends anti-obesity medications (AOMs) as adjuvant therapy for adults with both T2DM and overweight/obesity. In adults, the addition of AOMs to a diabetes regimen can improve glycemic control, reduce weight, and decrease anti-diabetes medication use. The ADA recommends considering bariatric surgery for adolescents with T2DM who have a BMI >35 kg/m2, but did not mention the use of AOMs in their 2022 updated guidelines. Currently, there are three FDA-approved AOMs available for chronic use in adolescents with obesity. Other medications are used in an “off-label” fashion for appetite suppression and BMI reduction. As additional AOMs are being developed and FDA-approved for the pediatric population, new treatment options with novel mechanisms of action will become available for adolescents with T2DM and obesity. In this review, we will discuss the evidence for the use of AOMs in the treatment of T2DM in adolescents, including lessons learned from the adult T2DM literature.
T3 levels and thyroid hormone signaling
Authors: Salas-Lucia Federico , Bianco Antonio C.
Published: October 2022

The clinical availability of tissue-specific biomarkers of thyroid hormone (TH) action constitutes a “holy grail” for the field. Scientists have investigated several TH-dependent markers, including the tissue content of triiodothyronine (T3)—the active form of TH. The study of animal models and humans indicates that the T3 content varies among different tissues, mostly due to the presence of low-affinity, high-capacity cytoplasmic T3 binding proteins. Nonetheless, given that T3 levels in the plasma and tissues are in equilibrium, T3 signaling is defined by the intracellular free T3 levels. The available techniques to assess tissue T3 are invasive and not clinically applicable. However, the tracer kinetic studies revealed that serum T3 levels can accurately predict tissue T3 content and T3 signaling in most tissues, except for the brain and pituitary gland. This is true not only for normal individuals but also for patients with hypo or hyperthyroidism–but not for patients with non-thyroidal illness syndrome. Given this direct relationship between serum and tissue T3 contents and T3 signaling in most tissues, clinicians managing patients with hypothyroidism could refocus attention on monitoring serum T3 levels. Future clinical trials should aim at correlating clinical outcomes with serum T3 levels.
Comparison of serum cytokines levels in normal-weight and overweight patients with first-episode drug-naïve major depressive disorder
Authors: Gao Wenfan , Xu Yayun , Liang Jun , Sun Yanhong , Zhang Yuanyuan , Shan Feng , Ge Jinfang , Xia Qingrong
Published: October 2022

Objective

Abnormal levels of blood cytokines have been demonstrated to be associated with both excess weight and major depressive disorder (MDD). However, few studies have addressed the direct effect of body mass index (BMI) on basal serum cytokines in individuals with first-episode drug-naïve MDD.

Methods

A total of 49 patients with first-episode drug-naïve MDD were categorized into normal weight (18.5 ≤ BMI < 25 kg/m2) and overweight (25 ≤ BMI < 30 kg/m2) groups according to WHO-criteria. The severity of depressive symptoms was assessed using the 24-items Hamilton Depression Scale (HAMD-24). A total of 37 cytokines were measured using Multiplex Luminex Assays. The scores of HAMD-24 and the levels of serum cytokines between normal weight group and overweight group were compared. Multiple linear regression analysis was performed to evaluate the association between abnormal serum cytokines levels and group after adjusting for HAMD-24 scores. The correlation between BMI and the scores of HAMD-24 and the levels of serum cytokines was evaluated using Pearson correlation analysis.

Results

The scores of HAMD-24 in overweight group were significantly higher than normal weight group (t = -2.930, P = 0.005). Moreover, the levels of IL-1α, IL-1RA, IL-3, CXCL10, TNF-α, and ICAM-1 in overweight patients with MDD were significantly higher than those in normal-weight patients with MDD (all P < 0.05). Furthermore, after adjustment for HAMD-24 scores, there was a significant correlation between abnormal serum cytokines levels (IL-1α, IL-1RA, IL-3, CXCL10, TNF-α, and ICAM-1) and group (all P < 0.05). Additionally, BMI was positively correlated to the serum levels of IL-1α (r = 0.428, P = 0.002), IL-3 (r = 0.529, P < 0.001), IL-6 (r = 0.285, P = 0.050), IL-10 (r = 0.423, P = 0.003), IL-12 (r = 0.367, P = 0.010), IL-15 (r = 0.300, P = 0.036), CXCL10 (r = 0.316, P = 0.030), TNF-α (r = 0.338, P = 0.021), and ICAM-1 (r = 0.440, P = 0.002) in MDD patients.

Conclusions

These results provide direct evidence, probably for the first time, that overweight may be associated with several serum cytokines in patients with first-episode drug-naïve MDD. The underlying mechanisms are unclear and require further investigation.
Light-induced synchronization of the SCN coupled oscillators and implications for entraining the HPA axis
Authors: Li Yannuo , Androulakis Ioannis P.
Published: October 2022

The suprachiasmatic nucleus (SCN) synchronizes the physiological rhythms to the external light-dark cycle and tunes the dynamics of circadian rhythms to photoperiod fluctuations. Changes in the neuronal network topologies are suggested to cause adaptation of the SCN in different photoperiods, resulting in the broader phase distribution of neuron activities in long photoperiods (LP) compared to short photoperiods (SP). Regulated by the SCN output, the level of glucocorticoids is elevated in short photoperiod, which is associated with peak disease incidence. The underlying coupling mechanisms of the SCN and the interplay between the SCN and the HPA axis have yet to be fully elucidated. In this work, we propose a mathematical model including a multiple-cellular SCN compartment and the HPA axis to investigate the properties of the circadian timing system under photoperiod changes. Our model predicts that the probability-dependent network is more energy-efficient than the distance-dependent network. Coupling the SCN network by intra-subpopulation and inter-subpopulation forces, we identified the negative correlation between robustness and plasticity of the oscillatory network. The HPA rhythms were predicted to be strongly entrained to the SCN rhythms with a pro-inflammatory high-amplitude glucocorticoid profile under SP. The fast temporal topology switch of the SCN network was predicted to enhance synchronization when the synchronization is not complete. These synchronization and circadian dynamics alterations might govern the seasonal variation of disease incidence and its symptom severity.
Plasma acylcarnitine and diabetic retinopathy: A study from Eastern China
Authors: Jin Dongzhen , Zhao Shuzhen , Li Huihui , Xia Zhezheng , Che Mingzhu , Huang Ruogu , Lai Mengyuan , Wang Yanan , Zhang Zejie , Wang Hui , Zuo Jingjing , Zheng Chao , Mao Guangyun
Published: October 2022

Background and purpose

Acylcarnitines (ACars) are important for insulin resistance and type 2 diabetes (T2D). However, their roles in diabetic retinopathy (DR) remain controversial. In this study, we aimed to investigate the association of ACars with DR and their values in DR detection.

Methods

This was a two-center case-control study based on the propensity score matching approach between August 2017 to June 2018 in Eastern China. Multivariable logistic regression models were applied to estimate the association of plasma ACars with DR. Differential ACars were screened by models of least absolute shrinkage and selection operator, elastic net, and weighted quantile sum regression, and their roles in DR identification were further evaluated by the area under the receiver operating curve (AUC).

Results

Eight of twenty plasma ACars (8:0, 12:0, 12:1, 14:1, 16:2, 18:0, 18:2 and 18:3) were associated with DR, while only ACar 8:0 was selected by three variable selection methods. As compared to those with the 1st tertile of ACar 8:0, the adjusted odds ratio (OR) and 95% confidence interval (CI) of DR were 0.22 (0.08, 0.59) and 0.12 (0.04, 0.36) for subjects in the 2nd and 3rd tertiles, respectively (P for trend < 0.001). Consistent associations were also observed in both restricted cubic spline regression models and subgroup analyses. AUC (95% CI) were 0.74 (0.66, 0.82) for ACar 8:0 alone and 0.77 (0.70, 0.85) for ACar 8:0 combined with covariates.

Conclusions

Our findings suggest higher ACar 8:0 is significantly associated with a decreased risk of DR, which provides a unique window for early identification of DR.
A novel signature based on pyroptosis-related genes for predicting prognosis and treatment response in prostate cancer patients
Authors: Xiao Xi , Li Jianpeng , Wan Shun , Wu Mingzhe , Li Zonglin , Tian Junqiang , Mi Jun
Published: October 2022

Background: Pyroptosis is a form of programmed cell death accompanied by specific inflammatory and immune responses, and it is closely related to the occurrence and progression of various cancers. However, the roles of pyroptosis-related genes (PRGs) in the prognosis, treatment response, and tumor microenvironment (TME) of prostate cancer (PCa) remain to be investigated.

Methods: The mRNA expression data and clinical information of PCa patients were obtained from the Cancer Genome Atlas database (TCGA) and the cBioPortal for Cancer Genomics website, and the 52 PRGs were obtained from the published papers. The univariate, multivariate, and LASSO Cox regression algorithms were used to obtain prognostic hub PRGs. Meanwhile, qRT-PCR was used to validate the expression of hub genes between PCa lines and normal prostate epithelial cell lines. We then constructed and validated a risk model associated with the patient’s disease-free survival (DFS). Finally, the relationships between risk score and clinicopathological characteristics, tumor immune microenvironment, and drug treatment response of PCa were systematically analyzed.

Results: A prognostic risk model was constructed with 6 hub PRGs (CHMP4C, GSDMB, NOD2, PLCG1, CYCS, GPX4), and patients were divided into high and low-risk groups by median risk score. The risk score was confirmed to be an independent prognostic factor for PCa in both the training and external validation sets. Patients in the high-risk group had a worse prognosis than those in the low-risk group, and they had more increased somatic mutations, higher immune cell infiltration and higher expression of immune checkpoint-related genes. Moreover, they were more sensitive to cell cycle-related chemotherapeutic drugs and might be more responsive to immunotherapy.

Conclusion: In our study, pyroptosis played a significant role in the management of the prognosis and tumor microenvironment of PCa. Meanwhile, the established model might help to develop more effective individual treatment strategies.
A novel asexual blood-stage malaria vaccine candidate: PfRipr5 formulated with human-use adjuvants induces potent growth inhibitory antibodies
Authors: Takashima Eizo , Nagaoka Hikaru , Correia Ricardo , Alves Paula M. , Roldão António , Christensen Dennis , Guderian Jeffrey A. , Fukushima Akihisa , Viebig Nicola K. , Depraetere Hilde , Tsuboi Takafumi
Published: October 2022

PfRipr is a highly conserved asexual-blood stage malaria vaccine candidate against Plasmodium falciparum. PfRipr5, a protein fragment of PfRipr inducing the most potent inhibitory antibodies, is a promising candidate for the development of next-generation malaria vaccines, requiring validation of its potential when formulated with adjuvants already approved for human use. In this study, PfRipr5 antigen was efficiently produced in a tank bioreactor using insect High Five cells and the baculovirus expression vector system; purified PfRipr5 was thermally stable in its monomeric form, had high purity and binding capacity to functional monoclonal anti-PfRipr antibody. The formulation of purified PfRipr5 with Alhydrogel®, GLA-SE or CAF®01 adjuvants accepted for human use showed acceptable compatibility. Rabbits immunized with these formulations induced comparable levels of anti-PfRipr5 antibodies, and significantly higher than the control group immunized with PfRipr5 alone. To investigate the efficacy of the antibodies, we used an in vitro parasite growth inhibition assay (GIA). The highest average GIA activity amongst all groups was attained with antibodies induced by immunization with PfRipr5 formulated with CAF®01. Overall, this study validates the potential of adjuvanted PfRipr5 as an asexual blood-stage malaria vaccine candidate, with PfRipr5/CAF®01 being a promising formulation for subsequent pre-clinical and clinical development.
Distinct immune and inflammatory response patterns contribute to the identification of poor prognosis and advanced clinical characters in bladder cancer patients
Authors: Chang Zhenglin , Li Rongqi , Zhang Jinhu , An Lingyue , Zhou Gaoxiang , Lei Min , Deng Jiwang , Yang Riwei , Song Zhenfeng , Zhong Wen , Qi Defeng , Duan Xiaolu , Li Shujue , Sun Baoqing , Wu Wenqi
Published: October 2022

Due to the molecular heterogeneity, most bladder cancer (BLCA) patients show no pathological responses to immunotherapy and chemotherapy yet suffer from their toxicity. This study identified and validated three distinct and stable molecular clusters of BLCA in cross-platform databases based on personalized immune and inflammatory characteristics. H&E-stained histopathology images confirmed the distinct infiltration of immune and inflammatory cells among clusters. Cluster-A was characterized by a favorable prognosis and low immune and inflammatory infiltration but showed the highest abundance of prognosis-related favorable immune cell and inflammatory activity. Cluster-B featured the worst prognosis and high immune infiltration, but numerous unfavorable immune cells exist. Cluster-C had a favorable prognosis and the highest immune and inflammatory infiltration. Based on machine learning, a highly precise predictive model (immune and inflammatory responses signature, IIRS), including FN1, IL10, MYC, CD247, and TLR2, was developed and validated to identify the high IIRS-score group that had a poor prognosis and advanced clinical characteristics. Compared to other published models, IIRS showed the highest AUC in 5 years of overall survival (OS) and a favorable predictive value in predicting 1- and 3- year OS. Moreover, IIRS showed an excellent performance in predicting immunotherapy and chemotherapy’s response. According to immunohistochemistry and qRT-PCR, IIRS genes were differentially expressed between tumor tissues with corresponding normal or adjacent tissues. Finally, immunohistochemical and H&E-stained analyses were performed on the bladder tissues of 13 BLCA patients to further demonstrate that the IIRS score is a valid substitute for IIR patterns and can contribute to identifying patients with poor clinical and histopathology characteristics. In conclusion, we established a novel IIRS depicting an IIR pattern that could independently predict OS and acts as a highly precise predictive biomarker for advanced clinical characters and the responses to immunotherapy and chemotherapy.
Differential activation of human neutrophils by SARS-CoV-2 variants of concern
Authors: Lebourgeois Samuel , David Ambroise , Chenane Houssem Redha , Granger Vanessa , Menidjel Reyene , Fidouh Nadhira , Noël Benoît , Delelis Olivier , Richetta Clémence , Charpentier Charlotte , Chollet-Martin Sylvie , Descamps Diane , Visseaux Benoit , de Chaisemartin Luc
Published: October 2022

The emerging SARS-CoV-2 virus has affected the entire world with over 600 million confirmed cases and 6.5 million deaths as of September 2022. Since the beginning of the pandemic, several variants of SARS-CoV-2 have emerged, with different infectivity and virulence. Several studies suggest an important role of neutrophils in SARS-Cov-2 infection severity, but data about direct activation of neutrophils by the virus is scarce. Here, we studied the in vitro activation of human neutrophils by SARS-CoV-2 variants of concern (VOCs). In our work, we show that upon stimulation with SARS-Cov-2 infectious particles, human healthy resting neutrophils upregulate activation markers, degranulate IL-8, produce Reactive Oxygen Species and release Neutrophil Extracellular Traps. Neutrophil activation was dependent on TLR7/8 and IRF3/STING. We then compared the activation potential of neutrophils by SARS-CoV-2 variants and showed a significantly increased activation by the Delta variant and a decreased activation by the Omicron variant as compared to the initial strain. In this study, we demonstrate that the SARS-Cov-2 virus can directly activate neutrophils in COVID-19 and that the different VOCs had differences in neutrophil activation intensity that mirror the differences of clinical severity. These data highlight the need to address neutrophil-virus interactions as a potential target for therapeutic intervention in SARS-CoV-2 infection.
Respiratory virus type to guide predictive enrichment approaches in the management of the first episode of bronchiolitis: A systematic review
Authors: Ambrożej Dominika , Makrinioti Heidi , Whitehouse Abigail , Papadopoulos Nikolas , Ruszczyński Marek , Adamiec Aleksander , Castro-Rodriguez Jose A. , Alansari Khalid , Jartti Tuomas , Feleszko Wojciech
Published: October 2022

It has become clear that severe bronchiolitis is a heterogeneous disease; even so, current bronchiolitis management guidelines rely on the one-size-fits-all approach regarding achieving both short-term and chronic outcomes. It has been speculated that the use of molecular markers could guide more effective pharmacological management and achieve the prevention of chronic respiratory sequelae. Existing data suggest that asthma-like treatment (systemic corticosteroids and beta2-agonists) in infants with rhinovirus-induced bronchiolitis is associated with improved short-term and chronic outcomes, but robust data is still lacking. We performed a systematic search of PubMed, Embase, Web of Science, and the Cochrane’s Library to identify eligible randomized controlled trials to determine the efficacy of a personalized, virus-dependent application of systemic corticosteroids in children with severe bronchiolitis. Twelve studies with heterogeneous methodology were included. The analysis of the available results comparing the respiratory syncytial virus (RSV)-positive and RSV-negative children did not reveal significant differences in the associatons between systemic corticosteroid use in acute episode and duration of hospitalization (short-term outcome). However, this systematic review identified a trend of the positive association between the use of systematic corticosteroids and duration of hospitalization in RSV-negative infants hospitalized with the first episode of bronchiolitis (two studies). This evidence is not conclusive. Taken together, we suggest the design for future studies to assess the respiratory virus type in guiding predictive enrichment approaches in infants presenting with the first episode of bronchiolitis.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42020173686