bluuebunny/crossref_metadata_2025 huggingface dataset:
Design and Modelling of a Compact Triband Passband Filter for GPS, WiMAX, and Satellite Applications with Multiple Transmission Zero’s
Authors: Basit Abdul , Daraz Amil , Khan Muhammad , Zubir Farid , A. AlQahtani Salman , Zhang Guoqiang
Published: June 2023

Designing microwave filters with high selectivity and sharp roll-off between the stop and pass bands can be challenging due to the complex nature of the R.F. signals and the requirements for achieving high performance in a limited physical space. To achieve a high selectivity and sharp roll-off rate, this paper presents a compact filter with a triple passband response. The two different passbands at 1.57 GHz and 3.5 GHz are achieved using a step impedance resonator (SIR) with metallic slots perturbation added to the lower corner of the high impedance section of the SIRs, which helps to enhance the filter’s selectivity and size reduction greatly. The embedded L-shaped structure originates a third passband at 4.23 GHz, resulting in a triband response with eight transmission zeros below and above the passbands at 1.22/1.42/1.98/3.18/3.82/3.98/4.38/4.53 GHz, respectively. The prototype has low signal attenuation of <1.2 dB and high signal reflection of >25 dB for the three passbands. The fractional bandwidths achieved are 2.54%, 4.2%, and 1.65% at 1.57/3.57/4.23 GHz, respectively, with rejection levels in the stopband greater than 15 dB. Lastly, the structure is fabricated on RO-4350B PCB and observed good matching between experimental and measured results. This demonstrates that the prototype can be successfully implemented in real-world applications such as GPS, WiMAX, and Satellite systems. The area occupied by the filter on a substrate or in a circuit is 0.31 λg × 0.24 λg, where λg is the guided wavelength of the material calculated at the lowest frequency.
Stakeholder Discourse on Synthetic Fuels: A Positioning and Narrative Analysis
Authors: Scheer Dirk , Schmieder Lisa
Published: June 2023

The transition of mobility (in German “Verkehrswende”) as a fundamental part of the overall energy transition is a controversial field among stakeholders—in particular when it comes to synthetic fuels. There are considerable opposing views on the pros and cons of synthetic fuels within stakeholder communication. Against this background, the aim of this study was to research stakeholder positions and communication by identifying, systemizing, and assessing the bandwidth of stakeholder statements and views in Germany using a document-based positioning analysis. The objective was to provide the broadest possible range of (controversial) assessments on synthetic fuels’ future pathways. Based on a document analysis of 41 sources published by 17 stakeholders from the areas of economy, environment, and civil society in the last ten years, we analyzed commonalities and differences in the assessments of the synthetic fuels’ path as well as the reasons behind it. The results were synthesized in three narrative frames dominating the German discourse on synthetic fuels, namely: (1) synthetic fuels as a key component for the mobility transition; (2) synthetic fuels as an essential strategic niche management component, and (3) mobility transition as sustainable, affordable, safe, and comfortable mobility—with or without synthetic fuels.
Biomarkers in Breast Cancer: An Old Story with a New End
Authors: Neves Rebello Alves Lyvia , Dummer Meira Débora , Poppe Merigueti Luiza , Correia Casotti Matheus , do Prado Ventorim Diego , Ferreira Figueiredo Almeida Jucimara , Pereira de Sousa Valdemir , Cindra Sant’Ana Marllon , Gonçalves Coutinho da Cruz Rahna , Santos Louro Luana , Mendonça Santana Gabriel , Erik Santos Louro Thomas , Evangelista Salazar Rhana , Ribeiro Campos da Silva Danielle , Stefani Siqueira Zetum Aléxia , Silva dos Reis Trabach Raquel , Imbroisi Valle Errera Flávia , de Paula Flávia , de Vargas Wolfgramm dos Santos Eldamária , Fagundes de Carvalho Elizeu , Drumond Louro Iúri
Published: June 2023

Breast cancer is the second most frequent cancer in the world. It is a heterogeneous disease and the leading cause of cancer mortality in women. Advances in molecular technologies allowed for the identification of new and more specifics biomarkers for breast cancer diagnosis, prognosis, and risk prediction, enabling personalized treatments, improving therapy, and preventing overtreatment, undertreatment, and incorrect treatment. Several breast cancer biomarkers have been identified and, along with traditional biomarkers, they can assist physicians throughout treatment plan and increase therapy success. Despite the need of more data to improve specificity and determine the real clinical utility of some biomarkers, others are already established and can be used as a guide to make treatment decisions. In this review, we summarize the available traditional, novel, and potential biomarkers while also including gene expression profiles, breast cancer single-cell and polyploid giant cancer cells. We hope to help physicians understand tumor specific characteristics and support decision-making in patient-personalized clinical management, consequently improving treatment outcome.
A Study of the Genetic Structure of Hybrid Camels in Kazakhstan
Authors: Amandykova Makpal , Dossybayev Kairat , Mussayeva Aizhan , Saitou Naruya , Zhunusbayeva Zhazira , Bekmanov Bakytzhan
Published: June 2023

Camel farming is gaining scientific interest due to its unique agricultural characteristics. Camels are versatile for milk and meat production, wool, racing, transport, and tourism. To use their full potential, it is essential to improve our understanding of the genetic structure of these animals. One-humped and two-humped camels have received detailed genetic descriptions, while there is no such information for their hybrids, which outperform their parent species in several agricultural characteristics. Thus, in this study, for the first time, the whole genome sequencing data (WGS) of five hybrid camels bred in the Almaty region of Kazakhstan are presented in comparison with the WGS data of one-humped, two-humped, and wild camels. A total of 43,552,164 single-nucleotide polymorphisms were found across the studied groups. Further comparison of these SNPs showed the following number of private SNPs among the populations: hybrid camels (3,271,083), wild camels (2,515,591), Bactrians (1,244,694), and dromedaries (531,224). The genetic structure of the studied animals was described, and a phylogenetic tree was built to assess their genetic distance. It was found that the studied hybrids are genetically closer to dromedaries since they were on the close branch of the phylogenetic tree.
Posterior Vertebral Pedicular Tethering for the Treatment of Idiopathic Adolescent Scoliosis
Authors: Mineiro Jorge
Published: June 2023

Over the last decade, there has been a new wave of interest in non-fusion techniques for the treatment of adolescent idiopathic scoliosis. These are not new techniques, as they were first published and presented in the late 1950s, using compression of the convexity or distraction of the concavity of the main curvature. More recently, anterior vertebral body tethering has raised great interest, as although it is a major procedure through the child’s chest, it seems appropriate for the thoracic curves. The main objective of this article is to describe Posterior Vertebral Pedicular Tethering (PVPT) as a “new” technique performed as a less invasive spinal procedure for the treatment of certain thoracolumbar and lumbar scoliosis in growing adolescents. It is an alternative growth modulation technique appropriate for thoracolumbar and lumbar curvatures where we observe reduction of the three plane deformity of idiopathic scoliosis in adolescents.
Research Progress of Chromosome Doubling and 2n Gametes of Ornamental Plants
Authors: Cui Luomin , Liu Zemao , Yin Yunlong , Zou Yiping , Faizan Mohammad , Alam Pravej , Yu Fangyuan
Published: June 2023

Polyploid plants, an important source for the selection of ornamental plants for their advantages of faster growth, higher yields, and stronger adaptability to an adverse environment, play an essential role in the development of economic plants for agricultural stress. The methodology has been improved to decrease blindness and increase the efficiency of ornamental plants’ polyploid breeding in the long term. The progress of research on ornamental plants related to natural polyploidy, chromosome doubling, the 2n gametes pathway, and plant ploidy identification are reviewed in this paper. The main routes in polyploid breeding are chromosome doubling and sexual hybridization. Screening of suitable induction methods and plant material should be enhanced in chromosome doubling to improve induction efficiency. Regarding polyploid breeding, the utilization and research on 2n gametes produced by natural conditions or artificial induction should be strengthened to shorten the breeding years. Therefore, further research should strengthen the combination of chromosome doubling and sexual hybridization to improve breeding efficiency and strengthen the research and application of polyploid plants. This thesis review provides some reference value for polyploid breeding in ornamental plants.
Post-Traumatic Stress Associated with Telework-Related Job Limitation in Latin America
Authors: Briceño Mariluz , Noblejas Grecia , Armada Jose , Serna-Alarcón Victor , Vilela-Estrada Martín A. , Vera-Ponce Víctor Juan , Valladares-Garrido Mario J. , Mejia Christian R.
Published: June 2023

During the pandemic, there has been evidence of work limitations during telework, which are believed to cause mental health problems. Our objective was to assess the association between perceived work limitations during telework and posttraumatic stress during the COVID-19 pandemic in Latin America. A cross-sectional study was conducted in Latin America in 2020. Exposure was measured by self-reporting using a self-perception questionnaire; the SPRINT-E questionnaire was used for outcome measurements. Generalized linear models were applied. Of 1329 participants, 15.2% (n = 202) had posttraumatic stress. In a multivariate analysis, the highest frequency of posttraumatic stress was found among those with moderate depression or more (PR = 1.29; 95% CI: 1.03–1.61), moderate or more anxiety (PR = 2.34; 95% CI: 1.61–3.41), and moderate or more stress (PR = 2.45; 95% CI: 1.46–4.12). In conclusion, there is an association between perceived work limitations during telework and posttraumatic stress in Latin American workers. For this reason, it is recommended that occupational physicians, companies, and institutions assess the frequency of posttraumatic stress and monitor the mental health of workers.
Intimate Partner Violence in Khaliji Women: A Review of the Frequency and Related Factors
Authors: Al Kiyumi Maisa H. , Al Shidhani Asma Said , Al Sumri Hana , Al Saidi Yaqoub , Al Harrasi Amira , Al Kiyumi Maryam , Al Sumri Sanaa , Al Toubi Aseel , Shetty Maithili , Al-Adawi Samir
Published: June 2023

The Gulf Cooperation Council (GCC), locally known as Khaliji, is a group of six Arab nations, including Saudi Arabia, Bahrain, Kuwait, Oman, Qatar, and the United Arab Emirates (UAE). Intimate partner violence (IPV) is a significant public health concern in the aforementioned region, but research that synthesises this trend has remained scarce. The present narrative review examines existing research on the prevalence and frequency of IPV among Khaliji women who inhabit the GCC nations. This review synthesised studies on physical and sexual violence, emotional abuse, and controlling behaviours perpetrated by an intimate partner. The prevalence rates of IPV among Khaliji women were observed to be high: women reported facing different types of abuse from their partners, namely physical (7–71%), sexual (3.7–81%), financial (21.3–26%), and psychological (7.5–89%), which is a culmination of controlling behaviour (36.8%), emotional violence (22–69%), and social violence (34%). Existing studies in the GCC region suggest that the most endorsed IPV was psychological abuse (89%), followed by sexual violence (81%). Qualitative analysis of the content of associated factors resulted in four significant descriptors, such as victim demographics, sociocultural factors, socioeconomic factors, and perpetrator-related issues. Research on IPV is still in its nascent stages, with very few studies emanating from the GCC region. The way forward will require developing culturally appropriate interventions that address the unique risk factors for IPV among the Khaliji population, strengthening institutional responses, and increasing awareness and social support for victims of IPV.
Triple Jeopardy of Minority Status, Social Stressors, and Health Disparities on Academic Performance of College Students
Authors: Becerra Monideepa B. , Gumasana Rushil J. , Mitchell Jasmine A. , Sami Saba , Truong Jeffrey Bao , Becerra Benjamin J.
Published: June 2023

Objective: In this study, we evaluated the role of minority status, as well as pandemic-related social stressors and health disparities on short- and long-term academic performances of college students. Methods: Cross-sectional analysis using descriptive and bivariate statistics were used to identify participants of minority status as well as pandemic-related prevalence of social stressors and health disparities and their roles on academic performance. Results: Poor academic performance was significantly related to being food insecure, experiences of discrimination, serious psychological distress, and low daytime wakefulness during the pandemic but only significantly based on minority status. Grade point average was significantly associated with serious psychological problems among males, independent of race/ethnicity identity. Conclusions: Institutes of higher education, when tasked with developing post-pandemic policies to address equity gaps in academic success, may benefit their students by integrating system-wide holistic approach to support, including interventions on basic needs support and health and resilience building.
A Rapid Review of Sociocultural Dimensions in Nigeria’s Solid Waste Management Approach
Authors: Akintayo Thomas , Hämäläinen Juha , Pasanen Pertti , John Iniobong
Published: June 2023

Against the background of an arguable dearth of scholarship on the sociocultural dimensions of Nigeria’s solid waste management strategies and practices, this rapid review searched for evidence in the literature. A rapid evidence review and qualitative meta-summary procedure were implemented to utilize the rigor of systematic literature review that met the timelines and limited funding available for this study. It is more appropriate to identify, extract, and synthesize a mixture of qualitative and/or quantitative empirical evidence in the literature. This rapid review found little substantive evidence of scholarly sociocultural approaches in Nigeria’s solid waste management. It also discovered constant factors of inadequate and weak multidisciplinary or non-holistic approaches to driving innovation and effective social impact in Nigeria’s solid waste management practices. The results were interpreted vis-à-vis the need to leverage the social sciences, particularly the range and scope of social work practice configurations and possibilities, to scientifically advance and substantially accelerate the implementation of evidence-based policy and practice in Nigeria’s solid waste management system. This rapid review concluded that the negative results are due to the insufficient conceptual and theoretical bases for Nigeria’s solid waste management strategies and/or practices.
Indocyanine Green (ICG)-Guided Onlay Preputial Island Flap Urethroplasty for the Single-Stage Repair of Hypospadias in Children: A Case Report
Authors: Paraboschi Irene , Gnech Michele , Minoli Dario Guido , De Marco Erika Adalgisa , Parente Giovanni , Mantica Guglielmo , Manzoni Gianantonio , Berrettini Alfredo
Published: June 2023

First described by Duckett in 1981, and initially employed for the surgical correction of mid-penile hypospadias, the onlay preputial island flap urethroplasty has progressively gained increasing popularity, extending its indication to proximal forms. However, with the complexity of the penile anomaly, the rate of postoperative complications related to poor tissue perfusion (including skin and glans dehiscence, urethral stenoses, and fistulas) has also increased. Conventionally, the visual assessment of the onlay preputial island flap is the only option available to establish the appropriate tissue vascularization during surgery. To this end, we have first introduced the EleVision IR system (Medtronic Ltd., Hong Kong, China) to assess the vascular perfusion of the preputial island flap in a 13-month-old boy undergoing the onlay urethroplasty for the surgical correction of a mid-shaft hypospadias. This was possible 80 s after the intravenous injection of indocyanine green (ICG, 0.15 mg/kg, Diagnostic Green GmbH, Munich, Germany). ICG-based laser angiography helped define the proximal resection margin of the preputial flap, and proved to be safe, effective, and easy to employ. This innovative intraoperative imaging modality can be considered a useful adjunct for tissue perfusion evaluation and intraoperative decision-making during the onlay preputial island flap urethroplasty in children.
Nationwide Survey on Seasonal Influenza Vaccination among Health Care Workers during the COVID-19 Pandemic in Greece: Determinants, Barriers and Peculiarities
Authors: Avakian Ioanna , Dadouli Katerina , Anagnostopoulos Lemonia , Fotiadis Konstantinos , Lianos Athanasios , Mina Paraskevi , Hadjichristodoulou Christos , Mouchtouri Varvara A.
Published: June 2023

Background: Seasonal influenza vaccination (SIV) of health care workers (HCWs) is critical in protecting patients’ and HCWs’ health. Our objective was to examine HCW SIV coverage and related determinants. Methods and Materials: A nationwide cross-sectional questionnaire survey was conducted among HCWs during the first half of 2021. The questionnaire (online or paper-based) included knowledge, attitude and practice questions regarding SIV, COVID-19 vaccines and vaccination. Results: Out of 6500 questionnaires administered, 2592 were completed (response rate: 39.9%). SIV coverage reached 69.4% (95% CI: 67.6–71.2%) based on self-reported vaccine uptake. Nurses and administrative staff were found to be more skeptical and have lower vaccine acceptance in comparison with physicians (aOR = 0.66 and aQR = 0.59, respectively). Other SIV hesitancy risk factors included working in secondary health care (aOR = 0.59) and working in northern Greece (aQR = 0.66). Determinants for SIV acceptance included being or living with high-risk people due to medical history (aOR = 1.84 and aOR = 1.46, respectively), positive attitudes towards routine vaccinations (aOR: 1.86), knowledge about COVID-19 vaccines (aOR = 1.53) and COVID-19 vaccine uptake (aOR = 3.45). The primary reason for SIV refusal was low risk perception (58.7%). Conclusions: SIV coverage (2020/2021) was relatively high, but remained far from formal recommendations. Specific occupational groups were skeptical and low-risk perception was the main reason for vaccine refusal. Targeted policies should be developed and enforced.
Does Diffusely Infiltrating Lobular Carcinoma of the Breast Arise from Epithelial–Mesenchymal Hybrid Cells?
Authors: Tabár László , Bozó Renáta , Dean Peter B. , Ormándi Katalin , Puchkova Olga , Oláh-Németh Orsolya , Németh István Balázs , Veréb Zoltán , Yen Ming-Fang , Chen Li-Sheng , Chen Hsiu-Hsi , Vörös András
Published: June 2023

Classic diffusely infiltrating lobular carcinoma has imaging features divergent from the breast cancers originating from the terminal ductal lobular units and from the major lactiferous ducts. Although the term “invasive lobular carcinoma” implies a site of origin within the breast lobular epithelium, we were unable to find evidence supporting this assumption. Exceptional excess of fibrous connective tissue and the unique cell architecture combined with the aberrant features at breast imaging suggest that this breast malignancy has not originated from cells lining the breast ducts and lobules. The only remaining relevant component of the fibroglandular tissue is the mesenchyme. The cells freshly isolated and cultured from diffusely infiltrating lobular carcinoma cases contained epithelial–mesenchymal hybrid cells with both epithelial and mesenchymal properties. The radiologic and histopathologic features of the tumours and expression of the mesenchymal stem cell positive markers CD73, CD90, and CD105 all suggest development in the direction of mesenchymal transition. These hybrid cells have tumour-initiating potential and have been shown to have poor prognosis and resistance to therapy targeted for malignancies of breast epithelial origin. Our work emphasizes the need for new approaches to the diagnosis and therapy of this highly fatal breast cancer subtype.
Brk/PTK6 and Involucrin Expression May Predict Breast Cancer Cell Responses to Vitamin D3
Authors: Box Carol , Pennington Caroline , Hare Stephen , Porter Sarah , Edwards Dylan , Eccles Suzanne , Crompton Mark , Harvey Amanda
Published: June 2023

The process of human embryonic mammary development gives rise to the structures in which mammary cells share a developmental lineage with skin epithelial cells such as keratinocytes. As some breast carcinomas have previously been shown to express high levels of involucrin, a marker of keratinocyte differentiation, we hypothesised that some breast tumours may de-differentiate to a keratinocyte-derived ‘evolutionary history’. To confirm our hypothesis, we investigated the frequency of involucrin expression along with that of Brk, a tyrosine kinase expressed in up to 86% of breast carcinomas whose normal expression patterns are restricted to differentiating epithelial cells, most notably those in the skin (keratinocytes) and the gastrointestinal tract. We found that involucrin, a keratinocyte differentiation marker, was expressed in a high proportion (78%) of breast carcinoma samples and cell lines. Interestingly, tumour samples found to express high levels of involucrin were also shown to express Brk. 1,25-dihydroxyvitamin D3, a known differentiation agent and potential anti-cancer agent, decreased proliferation in the breast cancer cell lines that expressed both involucrin and Brk, whereas the Brk/involucrin negative cell lines tested were less susceptible. In addition, responses to 1,25-dihydroxyvitamin D3 were not correlated with vitamin D receptor expression. These data contribute to the growing body of evidence suggesting that cellular responses to 1,25-dihydroxyvitamin D3 are potentially independent of vitamin D receptor status and provide an insight into potential markers, such as Brk and/or involucrin that could predict therapeutic responses to 1,25-dihydroxyvitamin D3.
Ameliorative Potential of (-) Pseudosemiglabrin in Mice with Pilocarpine-Induced Epilepsy: Antioxidant, Anti-Inflammatory, Anti-Apoptotic, and Neurotransmission Modulation
Authors: Balaha Mohamed F. , Alamer Ahmed A. , Abdel-Kader Maged S. , Alharthy Khalid M.
Published: June 2023

One prevalent neurological disorder is epilepsy. Modulating GABAergic/glutamatergic neurotransmission, Nrf2/HO-1, PI3K/Akt, and TLR-4/NF-B pathways might be a therapeutic strategy for epilepsy. Eight-week-old BALB/c mice were administered 12.5, 25, or 50 mg/kg (-) pseudosemiglabrin orally one hour before inducing epilepsy with an i.p. injection of 360 mg/kg pilocarpine. (-) Pseudosemiglabrin dose-dependently alleviated pilocarpine-induced epilepsy, as revealed by the complete repression of pilocarpine-induced convulsions and 100% survival rate in mice. Furthermore, (-) pseudosemiglabrin significantly enhanced mice’s locomotor activities, brain GABA, SLC1A2, GABARα1 levels, glutamate decarboxylase activity, and SLC1A2 and GABARα1mRNA expression while decreasing brain glutamate, SLC6A1, GRIN1 levels, GABA transaminase activity, and SLC6A1 and GRIN1 mRNA expression. These potentials can be due to the suppression of the TLR-4/NF-κB and the enhancement of the Nrf2/HO-1 and PI3K/Akt pathways, as demonstrated by the reduction in TLR-4, NF-κB, IL-1β, TNF-α mRNA expression, MDA, NO, caspase-3, Bax levels, and Bax/Bcl-2 ratio, and the enhancement of Nrf2, HO-1, PI3K, Akt mRNA expression, GSH, Bcl-2 levels, and SOD activity. Additionally, (-) pseudosemiglabrin abrogated the pilocarpine-induced histopathological changes. Interestingly, the (-) pseudosemiglabrin intervention showed a comparable effect to the standard medication, diazepam. Therefore, (-) pseudosemiglabrin can be a promising medication for the management of epilepsy.
Durvillaea antarctica: A Seaweed for Enhancing Immune and Cardiometabolic Health and Gut Microbiota Composition Modulation
Authors: Guerrero-Wyss Marion , Yans Caroline , Boscán-González Arturo , Duran Pablo , Parra-Soto Solange , Angarita Lissé
Published: June 2023

Durvillaea antarctica is the seaweed that is the most consumed by the Chilean population. It is recognized worldwide for its high nutritional value in protein, vitamins, minerals, and dietary fiber. This is a narrative review in which an extensive search of the literature was performed to establish the immunomodulator, cardiometabolic, and gut microbiota composition modulation effect of Durvillaea antarctica. Several studies have shown the potential of Durvillaea antarctica to function as prebiotics and to positively modulate the gut microbiota, which is related to anti-obesity, anti-inflammatory, anticancer, lipid-lowering, and hypoglycemic effects. The quantity of Bacteroides was negatively correlated with that of inflammatory monocytes and positively correlated with the levels of several gut metabolites. Seaweed-derived polysaccharides modulate the quantity and diversity of beneficial intestinal microbiota, decreasing phenol and p-cresol, which are related to intestinal diseases and the loss of intestinal function. Additionally, a beneficial metabolic effect related to this seaweed was observed, mainly promoting the decrease in the glycemic levels, lower cholesterol levels and cardiovascular risk. Consuming Durvillaea antarctica has a positive impact on the immune system, and its bioactive compounds provide beneficial effects on glycemic control and other metabolic parameters.
Correlation of the High-Resolution Computed Tomography Patterns of Intrathoracic Sarcoidosis with Serum Levels of SAA, CA 15.3, SP-D, and Other Biomarkers of Interstitial Lung Disease
Authors: Leštan Ramovš Zala , Sodin-Šemrl Snežna , Lakota Katja , Čučnik Saša , Manevski Damjan , Zbačnik Rok , Zupančič Mirjana , Verbič Martin , Terčelj Marjeta
Published: June 2023

Studies on the serum biomarkers of granulomatous inflammation and pulmonary interstitial disease in intrathoracic sarcoidosis have shown conflicting results. We postulated that differences in the concentrations of serum biomarkers can be explained by the heterogenous patterns of sarcoidosis seen on thoracic HRCT. Serum biomarker levels in 79 consecutive patients, newly diagnosed with intrathoracic sarcoidosis, were compared to our control group of 56 healthy blood donors. An analysis was performed with respect to HRCT characteristics (the presence of lymph node enlargement, perilymphatic or peribronchovascular infiltrates, ground-glass lesions, or fibrosis), CXR, and disease extent. Serum levels of CXCL9, CXCL10, CTO, and CCL18 were statistically significantly increased in all patients compared to controls. Serum levels of CA15.3 were statistically significantly increased in all patients with parenchymal involvement. SAA was increased in patients with ground-glass lesions while SP-D levels were statistically significantly increased in patients with lung fibrosis. Only SP-D and CA15.3 showed a significant correlation to interstitial disease extent. In conclusion, we found that sarcoidosis patients with different HRCT patterns of intrathoracic sarcoidosis have underlying biochemical differences in their serum biomarkers transcending Scadding stages. The stratification of patients based on both radiologic and biochemical characteristics could enable more homogenous patient selection for further prognostic studies.
Accelerated Bone Loss in Transgenic Mice Expressing Constitutively Active TGF-β Receptor Type I
Authors: Toejing Parichart , Sakunrangsit Nithidol , Pho-on Pinyada , Phetkong Chinnatam , Leelahavanichkul Asada , Sridurongrit Somyoth , Greenblatt Matthew B. , Lotinun Sutada
Published: June 2023

Transforming growth factor beta (TGF-β) is a key factor mediating the intercellular crosstalk between the hematopoietic stem cells and their microenvironment. Here, we investigated the skeletal phenotype of transgenic mice expressing constitutively active TGF-β receptor type I under the control of Mx1-Cre (Mx1;TβRICA mice). μCT analysis showed decreased cortical thickness, and cancellous bone volume in both femurs and mandibles. Histomorphometric analysis confirmed a decrease in cancellous bone volume due to increased osteoclast number and decreased osteoblast number. Primary osteoblasts showed decreased ALP and mineralization. Constitutive TβRI activation increased osteoclast differentiation. qPCR analysis showed that Tnfsf11/Tnfrsf11b ratio, Ctsk, Sufu, and Csf1 were increased whereas Runx2, Ptch1, and Ptch2 were decreased in Mx1;TβRICA femurs. Interestingly, Gli1, Wnt3a, Sp7, Alpl, Ptch1, Ptch2, and Shh mRNA expression were reduced whereas Tnfsf11/Tnfrsf11b ratio was increased in Mx1;TβRICA mandibles. Similarly, osteoclast-related genes were increased in Mx1;TβRICA osteoclasts whereas osteoblast-related genes were reduced in Mx1;TβRICA osteoblasts. Western blot analysis indicated that SMAD2 and SMAD3 phosphorylation was increased in Mx1;TβRICA osteoblasts, and SMAD3 phosphorylation was increased in Mx1;TβRICA osteoclasts. CTSK was increased while RUNX2 and PTCH1 was decreased in Mx1;TβRICA mice. Microindentation analysis indicated decreased hardness in Mx1;TβRICA mice. Our study indicated that Mx1;TβRICA mice were osteopenic by increasing osteoclast number and decreasing osteoblast number, possibly by suppressing Hedgehog signaling pathways.
Diagnostic and Prognostic Value of PACAP in Multiple Myeloma
Authors: Tóth Tünde , Alizadeh Hussain , Polgár Beáta , Csalódi Renáta , Reglődi Dóra , Tamás Andrea
Published: June 2023

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a multifunctional neuropeptide with well-known anti-inflammatory, antioxidant, antitumor, and immunomodulatory effects. PACAP regulates the production of various proinflammatory factors and may influence the complex cytokine network of the bone marrow microenvironment altered by plasma cells, affecting the progression of multiple myeloma (MM) and the development of end-organ damage. The aim of our study was to investigate the changes in PACAP-38 levels in patients with MM to explore its value as a potential biomarker in this disease. We compared the plasma PACAP-38 levels of MM patients with healthy individuals by ELISA method and examined its relationship with various MM-related clinical and laboratory parameters. Lower PACAP-38 levels were measured in MM patients compared with the healthy controls, however, this difference vanished if the patient achieved any response better than partial response. In addition, lower peptide levels were found in elderly patients. Significantly higher PACAP-38 levels were seen in patients with lower stage, lower plasma cell infiltration in bone marrow, lower markers of tumor burden in serum, lower total urinary and Bence-Jones protein levels, and in patients after lenalidomide therapy. Higher PACAP-38 levels in newly diagnosed MM patients predicted longer survival and a higher probability of complete response to treatment. Our findings confirm the hypothesis that PACAP plays an important role in the pathomechanism of MM. Furthermore, our results suggest that PACAP might be used as a valuable, non-invasive, complementary biomarker in diagnosis, and may be utilized for prognosis prediction and response monitoring.
Research Progress of Benzothiazole and Benzoxazole Derivatives in the Discovery of Agricultural Chemicals
Authors: Zou Yue , Zhang Yong , Liu Xing , Song Hongyi , Cai Qingfeng , Wang Sheng , Yi Chongfen , Chen Jixiang
Published: June 2023

Benzoxazole and benzothiazole have a broad spectrum of agricultural biological activities, such as antibacterial, antiviral, and herbicidal activities, which are important fused heterocyclic scaffold structures in agrochemical discovery. In recent years, great progress has been made in the research of benzoxazoles and benzothiazoles, especially in the development of herbicides and insecticides. With the widespread use of benzoxazoles and benzothiazoles, there may be more new products containing benzoxazoles and benzothiazoles in the future. We systematically reviewed the application of benzoxazoles and benzothiazoles in discovering new agrochemicals in the past two decades and summarized the antibacterial, fungicidal, antiviral, herbicidal, and insecticidal activities of the active compounds. We also discussed the structural–activity relationship and mechanism of the active compounds. This work aims to provide inspiration and ideas for the discovery of new agrochemicals based on benzoxazole and benzothiazole.
NIH/3T3 Fibroblasts Selectively Activate T Cells Specific for Posttranslationally Modified Collagen Type II
Authors: Dzhambazov Balik , Batsalova Tsvetelina , Merky Patrick , Lange Franziska , Holmdahl Rikard
Published: June 2023

It has been shown that synovial fibroblasts (SF) play a key role in the initiation of inflammation and joint destruction, leading to arthritis progression. Fibroblasts may express major histocompatibility complex class II region (MHCII) molecules, and thus, they could be able to process and present antigens to immunocompetent cells. Here we examine whether different types of fibroblasts (synovial, dermal, and thymic murine fibroblasts, destructive LS48 fibroblasts, and noninvasive NIH/3T3 fibroblasts) may be involved in the initiation of rheumatoid arthritis (RA) pathogenesis and can process and present type II collagen (COL2)—an autoantigen associated with RA. Using a panel of MHCII/Aq-restricted T-cell hybridoma lines that specifically recognize an immunodominant COL2 epitope (COL2259–273), we found that NIH/3T3 fibroblasts activate several T-cell clones that recognize the posttranslationally glycosylated or hydroxylated COL2259–273 epitope. The HCQ.3 hybridoma, which is specific for the glycosylated immunodominant COL2 epitope 259–273 (Gal264), showed the strongest response. Interestingly, NIH/3T3 cells, but not destructive LS48 fibroblasts, synovial, dermal, or thymic fibroblasts, were able to stimulate the HCQ.3 hybridoma and other COL2-specific T-cell hybridomas. Our experiments revealed that NIH/3T3 fibroblasts are able to activate COL2-specific T-cell hybridomas even in the absence of COL2 or a posttranslationally modified COL2 peptide. The mechanism of this unusual activation is contact-dependent and involves the T-cell receptor (TCR) complex.
Host–Microbiome Interactions: Tryptophan Metabolism and Aromatic Hydrocarbon Receptors after Traumatic Brain Injury
Authors: Sun Yanming , Wang Shuai , Liu Bingwei , Hu Wei , Zhu Ying
Published: June 2023

Traumatic brain injury refers to the damage caused to intracranial tissues by an external force acting on the head, leading to both immediate and prolonged harmful effects. Neuroinflammatory responses play a critical role in exacerbating the primary injury during the acute and chronic phases of TBI. Research has demonstrated that numerous neuroinflammatory responses are mediated through the “microbiota–gut–brain axis,” which signifies the functional connection between the gut microbiota and the brain. The aryl hydrocarbon receptor (AhR) plays a vital role in facilitating communication between the host and microbiota through recognizing specific ligands produced directly or indirectly by the microbiota. Tryptophan (trp), an indispensable amino acid in animals and humans, represents one of the key endogenous ligands for AhR. The metabolites of trp have significant effects on the functioning of the central nervous system (CNS) through activating AHR signalling, thereby establishing bidirectional communication between the gut microbiota and the brain. These interactions are mediated through immune, metabolic, and neural signalling mechanisms. In this review, we emphasize the co-metabolism of tryptophan in the gut microbiota and the signalling pathway mediated by AHR following TBI. Furthermore, we discuss the impact of these mechanisms on the underlying processes involved in traumatic brain injury, while also addressing potential future targets for intervention.
The Clinical Significance of Genetic Variation in Ovarian Cancer
Authors: Ban Dongjo , Housley Stephen N. , McDonald John F.
Published: June 2023

Genetic variation is a well-known contributor to the onset and progression of cancer. The goal of this study is to provide a comprehensive examination of the nucleotide and chromosomal variation associated with the onset and progression of serous ovarian cancer. Using a variety of computational and statistical methods, we examine the exome sequence profiles of genetic variants present in the primary tumors of 432 ovarian cancer patient samples to compute: (1) the tumor mutational burden for all genes and (2) the chromosomal copy number alterations associated with the onset/progression of ovarian cancer. Tumor mutational burden is reduced in the late vs. early stages, with the highest levels being associated with loss-of-function mutations in DNA-repair genes. Nucleotide variation and copy number alterations associated with known cancer driver genes are selectively favored over ovarian cancer development. The results indicate that genetic variation is a significant contributor to the onset and progression of ovarian cancer. The measurement of the relative levels of genetic variation associated with individual ovarian cancer patient tumors may be a clinically valuable predictor of potential tumor aggressiveness and resistance to chemotherapy. Tumors found to be associated with high levels of genetic variation may help in the clinical identification of high-risk ovarian cancer patients who could benefit from more frequent monitoring.
Plant Polyphenols Attenuate DSS-induced Ulcerative Colitis in Mice via Antioxidation, Anti-inflammation and Microbiota Regulation
Authors: Chen Huan , Li Ying , Wang Jinrui , Zheng Tingting , Wu Chenyang , Cui Mengyao , Feng Yifan , Ye Hanyi , Dong Zhengqi , Dang Yunjie
Published: June 2023

The pathogenesis of ulcerative colitis (UC) is associated with inflammation, oxidative stress, and gut microbiota imbalance. Although most researchers have demonstrated the antioxidant bioactivity of the phenolic compounds in plants, their UC-curing ability and underlying mechanisms still need to be further and adequately explored. Herein, we studied the antioxidation–structure relationship of several common polyphenols in plants including gallic acid, proanthocyanidin, ellagic acid, and tannic acid. Furthermore, the in vivo effects of the plant polyphenols on C57BL/6 mice with dextran-sulfate-sodium-induced UC were evaluated and the action mechanisms were explored. Moreover, the interplay of several mechanisms was determined. The higher the number of phenolic hydroxyl groups, the stronger the antioxidant activity. All polyphenols markedly ameliorated the symptoms and pathological progression of UC in mice. Furthermore, inflammatory cytokine levels were decreased and the intestinal barrier was repaired. The process was regulated by the antioxidant-signaling pathway of nuclear-erythroid 2-related factor 2. Moreover, the diversity of the intestinal microbiota, Firmicutes-to-Bacteroides ratio, and relative abundance of beneficial bacteria were increased. An interplay was observed between microbiota regulation and oxidative stress, immunity, and inflammatory response. Furthermore, intestinal barrier repair was found to be correlated with inflammatory responses. Our study results can form a basis for comprehensively developing plant-polyphenol-related medicinal products.
A2BAR Antagonism Decreases the Glomerular Expression and Secretion of Chemoattractants for Monocytes and the Pro-Fibrotic M2 Macrophages Polarization during Diabetic Nephropathy
Authors: Torres-Arévalo Ángelo , Nahuelpán Yéssica , Muñoz Katherin , Jara Claudia , Cappelli Claudio , Taracha-Wiśniewska Agnieszka , Quezada-Monrás Claudia , Martín Rody San
Published: June 2023

Some chemoattractants and leukocytes such as M1 and M2 macrophages are known to be involved in the development of glomerulosclerosis during diabetic nephropathy (DN). In the course of diabetes, an altered and defective cellular metabolism leads to the increase in adenosine levels, and thus to changes in the polarity (M1/M2) of macrophages. MRS1754, a selective antagonist of the A2B adenosine receptor (A2BAR), attenuated glomerulosclerosis and decreased macrophage-myofibroblast transition in DN rats. Therefore, we aimed to investigate the effect of MRS1754 on the glomerular expression/secretion of chemoattractants, the intraglomerular infiltration of leukocytes, and macrophage polarity in DN rats. Kidneys/glomeruli of non-diabetic, DN, and MRS1754-treated DN rats were processed for transcriptomic analysis, immunohistopathology, ELISA, and in vitro macrophage migration assays. The transcriptomic analysis identified an upregulation of transcripts and pathways related to the immune system in the glomeruli of DN rats, which was attenuated using MRS1754. The antagonism of the A2BAR decreased glomerular expression/secretion of chemoattractants (CCL2, CCL3, CCL6, and CCL21), the infiltration of macrophages, and their polarization to M2 in DN rats. The in vitro macrophages migration induced by conditioned-medium of DN glomeruli was significantly decreased using neutralizing antibodies against CCL2, CCL3, and CCL21. We concluded that the pharmacological blockade of the A2BAR decreases the transcriptional expression of genes/pathways related to the immune response, protein expression/secretion of chemoattractants, as well as the infiltration of macrophages and their polarization toward the M2 phenotype in the glomeruli of DN rats, suggesting a new mechanism implicated in the antifibrotic effect of MRS1754.
Overexpression of Hsp104 by Causing Dissolution of the Prion Seeds Cures the Yeast [PSI+] Prion
Authors: Stanford Katherine E. , Zhao Xiaohong , Kim Nathan , Masison Daniel C. , Greene Lois E.
Published: June 2023

The yeast Sup35 protein misfolds into the infectious [PSI+] prion, which is then propagated by the severing activity of the molecular chaperone, Hsp104. Unlike other yeast prions, this prion is unique in that it is efficiently cured by the overexpression as well as the inactivation of Hsp104. However, it is controversial whether curing by overexpression is due to the dissolution of the prion seeds by the trimming activity of Hsp104 or the asymmetric segregation of the prion seeds between mother and daughter cells which requires cell division. To answer this question, we conducted experiments and found no difference in the extent of curing between mother and daughter cells when half of the cells were cured by Hsp104 overexpression in one generation. Furthermore, curing was not affected by the lack of Sir2 expression, which was reported to be required for asymmetric segregation of the [PSI+] seeds. More importantly, when either hydroxyurea or ethanol were used to inhibit cell division, the extent of curing by Hsp104 overexpression was not significantly reduced. Therefore, the curing of [PSI+] by Hsp104 overexpression is not due to asymmetric segregation of the prion seeds, but rather their dissolution by Hsp104.
Association of Circulating Plasma Secreted Frizzled-Related Protein 5 (Sfrp5) Levels with Cardiac Function
Authors: Kelly Conagh J. , Chu Matthew , Untaru Rossana , Assadi-Khansari Bahador , Chen Dongqing , Croft Amanda J. , Horowitz John D. , Boyle Andrew J. , Sverdlov Aaron L. , Ngo Doan T. M.
Published: June 2023

Secreted frizzled-related protein 5 (SFRP5) is a novel anti-inflammatory adipokine that may play a role in cardiovascular development and disease. However, there is yet to be a comprehensive investigation into whether circulating SFRP5 can be a biomarker for cardiac function. Plasma SFRP5 levels were measured via ELISA in 262 patients admitted to a cardiology unit. Plasma SFRP5 levels were significantly lower in patients with a history of heart failure (HF), coronary artery disease (CAD), and atrial fibrillation (AF; p = 0.001). In univariate analyses, SFRP5 levels were also significantly positively correlated with left ventricular ejection fraction (LVEF) (r = 0.52, p < 0.001) and negatively correlated with E/E’ (r = −0.30, p < 0.001). Patients with HF, CAD, low LVEF, low triglycerides, high CRP, and high eGFR were associated with lower SFRP5 levels independent of age, BMI, or diabetes after multivariate analysis (overall model r = 0.729, SE = 0.638). Our results show that low plasma SFRP5 levels are independently associated with the presence of HF, CAD, and, importantly, impaired LV function. These results suggest a potential role of SFRP5 as a biomarker, as well as a mediator of cardiac dysfunction independent of obesity and metabolic regulation.
Myocardial Blush Grade Predicts Postoperative Atrial Fibrillation following Mitral Valve Replacement: A Novel Perspective
Authors: Çiçek Ömer Faruk , Esenboğa Kerim , Yalçın Muhammed Ulvi , Durdu Mustafa Serkan , Altunkeser Bülent Behlül , Büyükateş Mustafa
Published: June 2023

Background: Atrial fibrillation (AF) remains the most common arrhythmia following mitral valve surgery. Although numerous clinical and laboratory indicators and possible mechanisms of postoperative AF (PoAF) have been described, the role of microvascular dysfunction in pathogenesis has not been assessed. We aimed to evaluate the association between microvascular dysfunction and PoAF in patients undergoing isolated mitral valve replacement. Methods: 188 patients undergoing mitral valve replacement were included in this retrospective study. Demographic characteristics of the patients were recorded. Angiographic assessment of microvascular perfusion was performed using the myocardial blush grading technique for each patient. Univariate and multivariate logistic regression analyses were utilized to determine predictors of PoAF. Results: Of 188 patients (56.69 ± 8.9 years, 39.4% male) who underwent mitral valve replacement, 64 (34%) patients developed PoAF. In the PoAF group, a lower basal hemoglobin level (12.64 ± 0.89 vs. 14.46 ± 0.91 g/dL; p < 0.001), a higher left atrial diameter [5.9 (5.2–6.47) vs. 4.9 (4.5–5.8) cm; p < 0.001], and a lower total blush score (TBS) (8.33 ± 0.84 vs. 8.9 ± 0.31; p < 0.001) were detected. Multivariate logistic regression analysis revealed that preoperative LA diameter (OR:2.057; 95% CI: 1.166–3.63; p = 0.013), preoperative hemoglobin (OR:0.12; 95% CI: 0.058–0.245; p < 0.001), and abnormal TBS (OR:15.1; 95% CI: 1.602–142.339; p = 0.018) were independent predictors of PoAF. Conclusions: Our findings demonstrated that TBS at the preoperative period was an independent predictor of PoAF in patients undergoing isolated mitral valve replacement.