bluuebunny/crossref_metadata_2025 huggingface dataset:
Compliance to Guidelines in Prescribing Empirical Antibiotics for Individuals with Uncomplicated Urinary Tract Infection in a Primary Health Facility of Ghana, 2019–2021
Authors: Owusu Helena , Thekkur Pruthu , Ashubwe-Jalemba Jacklyne , Hedidor George Kwesi , Corquaye Oksana , Aggor Asiwome , Steele-Dadzie Allen , Ankrah Daniel
Published: September 2022

Increasing trends in antimicrobial resistance among uropathogens call for rational use of empirical antibiotics for managing uncomplicated urinary tract infections (UTIs). In Ghana, standard treatment guidelines (STGs) for UTI recommend oral ciprofloxacin or cefuroxime for 5–7 days in females and 10–14 days in males. We conducted a cross-sectional audit using electronic medical records (EMR) to assess compliance to the STGs among adults (≥18 years) with uncomplicated UTIs diagnosed in a primary health facility between October 2019 and October 2021. Among 3717 patients, 71% were females and all had complete prescription details in the EMR. Of all the patients, 83% were prescribed empirical antibiotics, of whom 88% received oral ciprofloxacin or cefuroxime. Only 68% were prescribed antibiotics for the correct duration, which was significantly lower among males (10%) compared to females (90%). Among patients who received antibiotics, 60% were prescribed in line with the STGs. The results call for feedback to physicians about poor compliance to STGs with duration of antibiotic prescribed. Recommendations on 10–14 days duration of antibiotics for males needs to be reassessed and necessary amendments to STGs can be made. Leveraging the well-established EMR system, a real-time audit-feedback mechanism can be instituted to improve compliance with STGs.
Investigating Outcomes of a Family Strengthening Intervention for Resettled Somali Bantu and Bhutanese Refugees: An Explanatory Sequential Mixed Methods Study
Authors: Neville Sarah Elizabeth , DiClemente-Bosco Kira , Chamlagai Lila K. , Bunn Mary , Freeman Jordan , Berent Jenna M. , Gautam Bhuwan , Abdi Abdirahman , Betancourt Theresa S.
Published: September 2022

Pre- and post-migration stressors can put resettled refugee children at risk of poor mental health outcomes. The Family Strengthening Intervention for Refugees (FSI-R) is a peer-delivered preventative home visiting program for resettled refugees that aims to draw upon families’ strengths to foster improved family communication, positive parenting, and caregiver-child relationships, with the ultimate goal of reducing children’s risk of mental health problems. Using an explanatory sequential mixed methods design, this study draws upon qualitative interviews with caregivers (n = 19) and children (n = 17) who participated in a pilot study of the FSI-R intervention in New England, as well as interventionists (n = 4), to unpack quantitative findings on mental health and family functioning from a randomized pilot study (n = 80 families). Most patterns observed in the quantitative data as published in the pilot trial were triangulated by qualitative data. Bhutanese caregivers and children noted that children were less shy or scared to speak up after participating in the FSI-R. Somali Bantu families spoke less about child mental health and underscored feasibility challenges like language barriers between caregivers and children. Interventionists suggested that families with higher levels of education were more open to implementing behavior change. In both groups, families appreciated the intervention and found it to be feasible and acceptable, but also desired additional help in addressing broader family and community needs such as jobs and literacy programs.
Assessment of the Best FEA Failure Criteria (Part I): Investigation of the Biomechanical Behavior of PDL in Intact and Reduced Periodontium
Authors: Moga Radu Andrei , Buru Stefan Marius , Olteanu Cristian Doru
Published: September 2022

The accuracy of five failure criterions employed in the study of periodontal ligaments (PDL) during periodontal breakdown under orthodontic movements was assessed. Based on cone-beam computed tomography (CBCT) examinations, nine 3D models of the second lower premolar with intact periodontium were created and individually subjected to various levels of horizontal bone loss. 0.5 N of intrusion, extrusion, rotation, tipping, and translation was applied. A finite Elements Analysis (FEA) was performed, and stresses were quantitatively and qualitatively analyzed. In intact periodontium, Tresca and Von Mises (VM) stresses were lower than maximum physiological hydrostatic pressure (MHP), while maximum principal stress S1, minimum principal stress S3, and pressure were higher. In reduced periodontium, Tresca and VM stresses were lower than MHP for intrusion, extrusion, and the apical third of the periodontal ligament for the other movements. 0.5 N of rotation, translation and tipping induced cervical third stress exceeding MHP. Only Tresca (quantitatively more accurate) and VM are adequate for the study of PDL (resemblance to ductile), being qualitatively similar. A 0.5 N force seems safe in the intact periodontium, and for intrusion and extrusion up to 8 mm bone loss. The amount of force should be reduced to 0.1–0.2 N for rotation, 0.15–0.3 N for translation and 0.2–0.4 N for tipping in 4–8 mm periodontal breakdown. S1, S3, and pressure criteria provided only qualitative results.
Local Government Debt and Green Total Factor Productivity—Empirical Evidence from Chinese Cities
Authors: Mao Ke , Failler Pierre
Published: September 2022

In recent years, the expansion of local government debt (LGD) in China has caused widespread concern. Enhancing green total factor productivity (GTFP) is an important way to coordinate resources, environment, and regional development and is an important indicator to realize the transformation of green economic development. Scientific assessment of the impact of LGD on GTFP helps promote the transformation of green economic development. This paper selects sample data from 271 cities in China from 2010 to 2019 and empirically investigates the mechanisms of LGD, green innovation, and financial market development on GTFP. The results show that (1) LGD expansion significantly suppresses GTFP in China; (2) green innovation mediates between the two, and LGD suppresses GTFP by reducing the level of green innovation; and (3) financial market development can mitigate the negative impact of LGD on urban GTFP. Therefore, the governance of LGD should be strengthened, the financial market environment should be optimized, the distortion of financial resources should be corrected, and innovative financing modes such as green finance and green credit should be encouraged to enhance GTFP.
Unveiling Frequently Co-Occurring Reasons of Attitudinal Acceptance of Intimate Partner Violence against Women: A Behavioral Data Science Perspective
Authors: Yasir Muhammad , Ashraf Ayesha , Chaudhry Muhammad Umar , Batool Syeda Azra , Batool Syeda Shahida , Jasinska Elzbieta , Leonowicz Zbigniew , Jasinski Michal
Published: September 2022

The results of gender equality indicators across the world in the form of prevalence of intimate partner violence (IPV) against women are striking and has thus drawn the attention of policy makers as well as necessitates the adoption of a comprehensive system to deal with. The situation of IPV in Pakistan is alarming. This study examines the acceptability attitude of women and men toward intimate partner violence against women through data science. It discovers and contrasts the frequently co-occurring reasons due to which husbands’ behaviour of beating their wives is believed to be legitimate by both partners in the province of Punjab, Pakistan. Though the discovered frequently co-occurring reasons, such as “arguing with the husband and neglecting the children” altogether, are similar in both genders but the fraction of wives believing in such reasons are significantly greater than that of husbands. This psychological disparity across genders could help in identifying the social and cultural factors to whom this disparity is attributed. It is expected that the identified co-occurring groups of reasons would help to understand the problem to the next level and devise better strategies to mitigate them.
Accessibility in People with Disabilities in Primary Healthcare Centers: A Dimension of the Quality of Care
Authors: Campillay-Campillay Maggie , Calle-Carrasco Ana , Dubo Pablo , Moraga-Rodríguez Jorge , Coss-Mandiola Juan , Vanegas-López Jairo , Rojas Alejandra , Carrasco Raúl
Published: September 2022

The purpose of this research is to evaluate universal accessibility in primary healthcare (PHC) centers in the Atacama region, Chile, through an analytical cross-sectional study with a quality approach, which uses the external audit model with the application of a dichotomous comparison guideline, evaluating levels of compliance with four dimensions of universal accessibility described in the literature: participation, information, accessibility chain and architectural aspects. This was carried out in 18 PHC, and set as Lower Control Limit (LCL) of 70% to compare levels of compliance, and a hierarchical model and k-mean analysis were applied. Results: Very low compliance averages were obtained, 37.7% participation, 4% information, 44.4% access chain, and 63.9% architectural aspects, indicating a critical situation. Moreover, the cluster comparison allowed to observe that a group of healthcare centers complies more than other groups, which requires more attention. Conclusions: The low level of accessibility for people with disabilities may be associated with various factors that require further monitoring and analysis. However, low levels of accessibility require changing the way of relating to this vulnerable group of the population, and considering including them in the design and reasonable adjustments made in PHC centers. The findings from this research open the possibility for future research that increases understanding of how to reduce barriers in a such wide variety of forms of disability.
Firefighters’ Clothing Contamination in Fires of Electric Vehicle Batteries and Photovoltaic Modules—Literature Review and Pilot Tests Results
Authors: Szmytke Ewelina , Brzezińska Dorota , Machnowski Waldemar , Kokot Szymon
Published: September 2022

The electric vehicle (EV) market, together with photovoltaic (PV) installations continues to develop at a pace. However, there are concerns that EV and PV installation fires may create more harmful substances than other types of fire. PV modules and car battery fires emit a range of carcinogenic and highly toxic compounds that are not yet fully understood and may pose a threat to firefighters’ health. This also raises the question of the impact on firefighters’ clothing and the safe handling and cleaning after such fires. This article presents a literature and standards review of the firefighters’ protective clothing maintenance and cleaning. It also contains test results showing that firefighters’ clothes accumulate harmful substances after fighting these types of fires. Pilot tests for the presence of polycyclic aromatic hydrocarbons (PAHs) and formaldehyde showed that levels exceeded limits in all clothing samples. For example, the cobalt level was 24 times higher than that considered safe in the test carried out with car battery fire. Although it is recognized that liquid carbon dioxide (LCO2) methods of cleaning may be more effective than traditional water washing, further research on cleaning efficiency for clothing containing substances emitted from car battery and PV modules fires is required.
Location Optimization of COVID-19 Vaccination Sites: Case in Hillsborough County, Florida
Authors: Chen Yuzhou , Tao Ran , Downs Joni
Published: September 2022

The equitable allocation of COVID-19 vaccines is a critical challenge worldwide, given that the pandemic has been disproportionally affecting economically disadvantaged racial and ethnic groups. In the United States, the ongoing implementation efforts at different administrative levels and districts, to some extent, are standing in conflict with commitments to mitigate inequities. In this study, we developed a spatial optimization model to choose the best locations for vaccination sites. The model is a modified two-step maximal covering location problem (MCLP). It aims at maximizing the number of residents who can conveniently access the sites and mitigating inequity issues by prioritizing disadvantaged population groups who live in geographic areas identified through the CDC’s Social Vulnerability Index (SVI). We conducted our study using the case of Hillsborough County, Florida. We found that by reserving up to 30% of total vaccines for highly vulnerable communities, our model can optimize location choices for vaccination sites to provide effective coverage for residents at large while prioritizing disadvantaged groups of people. A series of sensitivity analyses have been performed to evaluate the impact of parameters such as site capacity and distance threshold. The model has the potential to guide the future allocation of critical medical resources in the U.S. and other countries.
Relationship between World Assumptions and Post-Traumatic Growth among Polish Cancer Patients: Moderating Effect of Rumination
Authors: Szcześniak Małgorzata , Madej Daria , Bielecka Grażyna
Published: September 2022

Background: Although post-traumatic growth is believed to be the result of complex interplays between various factors, cognitive variables appear to play a special role in these interactions. Yet, research on this topic is scant. Therefore, the first purpose of this study was to verify whether there is a direct relationship between world assumptions and post-traumatic growth among Polish cancer patients. As the effect of psychological change in post-traumatic growth may be affected by basic beliefs about the world and oneself, the second goal was to assess whether this association is moderated by rumination. Methods: The study included 215 Polish cancer patients. The Post-traumatic Growth and Depreciation Inventory—Expanded version—(intrusive and deliberate rumination), the World Assumption Scale, and the Event-related Rumination Inventory were applied. Results: Positive, albeit weak, correlations were found between the dimensions of world assumptions and post-traumatic growth. Post-traumatic growth correlated negatively with intrusive rumination and positively with deliberate rumination. The outcomes show that the level of post-traumatic growth resulting from world assumptions is significantly different at various levels of intrusive and deliberate rumination. Conclusion: Lower/medium intrusive rumination seems to strengthen the relationship between benevolence of the world/worthiness of the self and post-traumatic growth, and higher deliberate rumination tends to reinforce the relationship between meaningfulness and post-traumatic growth.
Cultural Perspectives, Feelings and Coping Behaviors during the COVID-19 Pandemic: A Case Study of Romanian Students
Authors: Șimon Simona , Fărcașiu Marcela Alina , Dragomir Gabriel-Mugurel
Published: September 2022

Socio-cultural patterns and communication styles differ from culture to culture. As such, the way in which people deal with a crisis situation is also culture-dependent. The COVID-19 pandemic has pointed, once more, to the cultural diversity of the world through a variety of reactions to the measures imposed by the global spread of the deadly virus. The present research aims at identifying the feelings, coping behaviors and communication patterns of the younger Romanian generation during the COVID-19 pandemic and at explaining them from a cultural standpoint, in an effort to raise awareness of the cultural (un)predictability of human reactions to certain external stimuli. The survey conducted online on 409 students at Politehnica University of Timișoara (Romania) revealed that most of students’ socio-cultural behavior could have been anticipated by the Romanian authorities when they decided a certain pandemic action plan, and that the few unexpected results indicate the versatility of a culture that is still changing under the Western European influence caused by the fact that Romania has adhered to European Union principles for more than fifteen years.
Impact of a Novel PagR-like Transcriptional Regulator on Cereulide Toxin Synthesis in Emetic Bacillus cereus
Authors: Kalbhenn Eva Maria , Kranzler Markus , Gacek-Matthews Agnieszka , Grass Gregor , Stark Timo D. , Frenzel Elrike , Ehling-Schulz Monika
Published: September 2022

The emetic type of foodborne disease caused by Bacillus cereus is produced by the small peptide toxin cereulide. The genetic locus encoding the Ces nonribosomal peptide synthetase (CesNRPS) multienzyme machinery is located on a 270 kb megaplasmid, designated pCER270, which shares its backbone with the Bacillus anthracis toxin plasmid pXO1. Although the ces genes are plasmid-borne, the chromosomally encoded pleiotropic transcriptional factors CodY and AbrB are key players in the control of ces transcription. Since these proteins only repress cereulide synthesis during earlier growth phases, other factors must be involved in the strict control of ces expression and its embedment in the bacterial life cycle. In silico genome analysis revealed that pCER270 carries a putative ArsR/SmtB family transcription factor showing high homology to PagR from B. anthracis. As PagR plays a crucial role in the regulation of the protective antigen gene pagA, which forms part of anthrax toxin, we used a gene-inactivation approach, combined with electrophoretic mobility shift assays and a bacterial two-hybrid system for dissecting the role of the PagR homologue PagRBc in the regulation of cereulide synthesis. Our results highlight that the plasmid-encoded transcriptional regulator PagRBc plays an important role in the complex and multilayered process of cereulide synthesis.
Genetic Analysis and Fine Mapping of ZmGHT1 Conferring Glufosinate Herbicide Tolerance in Maize (Zea mays L.)
Authors: Bao Jianxi , Gao Yuexin , Li Yanan , Wu Suowei , Li Jinping , Dong Zhenying , Wan Xiangyuan
Published: September 2022

Weed interference in the crop field is one of the major biotic stresses causing dramatic crop yield losses, and the development of herbicide-resistant crops is critical for weed control in the application of herbicide technologies. To identify herbicide-resistant germplasms, we screened 854 maize inbreed lines and 25,620 seedlings by spraying them with 1 g/L glufosinate. One plant (L336R), possibly derived from a natural variation of line L336, was identified to have the potential for glufosinate tolerance. Genetic analysis validated that the glufosinate tolerance of L336R is conferred by a single locus, which was tentatively designated as ZmGHT1. By constructing a bi-parental population derived from L336R, and a glufosinate sensitive line L312, ZmGHT1 was mapped between molecular markers M9 and M10. Interestingly, genomic comparation between the two sequenced reference genomes showed that large scale structural variations (SVs) occurred within the mapped region, resulting in 2.16 Mb in the inbreed line B73, and 11.5 kb in CML277, respectively. During the fine mapping process, we did not detect any additional recombinant, even by using more than 9500 F2 and F3 plants, suspecting that SVs should also have occurred between L336R and L312 in this region, which inhibited recombination. By evaluating the expression of the genes within the mapped interval and using functional annotation, we predict that the gene Zm00001eb361930, encoding an aminotransferase, is the most likely causative gene. After glufosinate treatment, lower levels of ammonia content and a higher activity of glutamine synthetase (GS) in L336R were detected compared with those of L336 and L312, suggesting that the target gene may participate in ammonia elimination involving GS activity. Collectively, our study can provide a material resource for maize herbicide resistant breeding, with the potential to reveal a new mechanism for herbicide resistance.
CRISPR/Cas9—A Promising Therapeutic Tool to Cure Blindness: Current Scenario and Future Prospects
Authors: Ahmad Irshad
Published: September 2022

CRISPR-based targeted genome editing is bringing revolutionary changes in the research arena of biological sciences. CRISPR/Cas9 has been explored as an efficient therapeutic tool for the treatment of genetic diseases. It has been widely used in ophthalmology research by using mouse models to correct pathogenic mutations in the eye stem cells. In recent studies, CRISPR/Cas9 has been used to correct a large number of mutations related to inherited retinal disorders. In vivo therapeutic advantages for retinal diseases have been successfully achieved in some rodents. Current advances in the CRISPR-based gene-editing domain, such as modified Cas variants and delivery approaches have optimized its application to treat blindness. In this review, recent progress and challenges of the CRISPR-Cas system have been discussed to cure blindness and its prospects.
Pro-Apoptotic and Anti-Invasive Properties Underscore the Tumor-Suppressing Impact of Myoglobin on a Subset of Human Breast Cancer Cells
Authors: Aboouf Mostafa A. , Armbruster Julia , Thiersch Markus , Guscetti Franco , Kristiansen Glen , Schraml Peter , Bicker Anne , Petry Ruben , Hankeln Thomas , Gassmann Max , Gorr Thomas A.
Published: September 2022

The expression of myoglobin (MB), well known as the oxygen storage and transport protein of myocytes, is a novel hallmark of the luminal subtype in breast cancer patients and correlates with better prognosis. The mechanisms by which MB impacts mammary tumorigenesis are hitherto unclear. We aimed to unravel this role by using CRISPR/Cas9 technology to generate MB-deficient clones of MCF7 and SKBR3 breast cancer cell lines and subsequently characterize them by transcriptomics plus molecular and functional analyses. As main findings, loss of MB at normoxia upregulated the expression of cell cyclins and increased cell survival, while it prevented apoptosis in MCF7 cells. Additionally, MB-deficient cells were less sensitive to doxorubicin but not ionizing radiation. Under hypoxia, the loss of MB enhanced the partial epithelial to mesenchymal transition, thus, augmenting the migratory and invasive behavior of cells. Notably, in human invasive mammary ductal carcinoma tissues, MB and apoptotic marker levels were positively correlated. In addition, MB protein expression in invasive ductal carcinomas was associated with a positive prognostic value, independent of the known tumor suppressor p53. In conclusion, we provide multiple lines of evidence that endogenous MB in cancer cells by itself exerts novel tumor-suppressive roles through which it can reduce cancer malignancy.
Cultivation of Cryopreserved Human Dental Pulp Stem Cells—A New Approach to Maintaining Dental Pulp Tissue
Authors: Wang Wang , Yan Ming , Aarabi Ghazal , Peters Ulrike , Freytag Marcus , Gosau Martin , Smeets Ralf , Beikler Thomas
Published: September 2022

Human dental pulp stem cells (hDPSCs) are multipotent mesenchymal stem cells (MSCs) that are capable of self-renewal with multilineage differentiation potential. After being cryopreserved, hDPSCs were reported to maintain a high level of proliferation and multi-differentiation abilities. In order to optimize cryopreservation techniques, decrease storage requirements and lower contamination risks, the feasibility of new whole-tooth cryopreservation and its effects on hDPSCs were tested. The survival rates, morphology, proliferation rates, cell activity, surface antigens and differentiation abilities of hDPSCs isolated from fresh teeth were compared with those of one-month cryopreserved teeth in 5% and 10% DMSO. The data of the present study indicated that the new cryopreservation approach did not reduce the capabilities or stemness of hDPSCs, with the exception that it extended the first appearance time of hDPSCs in the teeth that were cryopreserved in 10% DMSO, and reduced their recovery rate. With the novel strategy of freezing, the hDPSCs still expressed the typical surface markers of MSCs and maintained excellent proliferation capacity. Three consecutive weeks of osteogenic and adipogenic induction also showed that the expression of the key genes in hDPSCs, including lipoprotein lipase (LPL), peroxisome proliferator-activated receptor-γ (PPAR-γ), alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), type I collagen (COL I) and osteocalcin (OSC) was not affected, indicating that their differentiation abilities remained intact, which are crucial parameters for hDPSCs as cell-therapy candidates. These results demonstrated that the new cryopreservation method is low-cost and effective for the good preservation of hDPSCs without compromising cell performance, and can provide ideas and evidence for the future application of stem-cell therapies and the establishment of dental banks.
Cellular Biogenetic Law and Its Distortion by Protein Interactions: A Possible Unified Framework for Cancer Biology and Regenerative Medicine
Authors: Vinogradov Alexander E. , Anatskaya Olga V.
Published: September 2022

The biogenetic law (recapitulation law) states that ontogenesis recapitulates phylogenesis. However, this law can be distorted by the modification of development. We showed the recapitulation of phylogenesis during the differentiation of various cell types, using a meta-analysis of human single-cell transcriptomes, with the control for cell cycle activity and the improved phylostratigraphy (gene dating). The multipotent progenitors, differentiated from pluripotent embryonic stem cells (ESC), showed the downregulation of unicellular (UC) genes and the upregulation of multicellular (MC) genes, but only in the case of those originating up to the Euteleostomi (bony vertebrates). This picture strikingly resembles the evolutionary profile of regulatory gene expansion due to gene duplication in the human genome. The recapitulation of phylogenesis in the induced pluripotent stem cells (iPSC) during their differentiation resembles the ESC pattern. The unipotent erythroblasts differentiating into erythrocytes showed the downregulation of UC genes and the upregulation of MC genes originating after the Euteleostomi. The MC interactome neighborhood of a protein encoded by a UC gene reverses the gene expression pattern. The functional analysis showed that the evolved environment of the UC proteins is typical for protein modifiers and signaling-related proteins. Besides a fundamental aspect, this approach can provide a unified framework for cancer biology and regenerative/rejuvenation medicine because oncogenesis can be defined as an atavistic reversal to a UC state, while regeneration and rejuvenation require an ontogenetic reversal.
Jellyfish Polysaccharides for Wound Healing Applications
Authors: Migone Chiara , Scacciati Noemi , Grassiri Brunella , De Leo Marinella , Braca Alessandra , Puppi Dario , Zambito Ylenia , Piras Anna Maria
Published: September 2022

Jellyfishes are considered a new potential resource in food, pharmaceutical and biomedical industries. In these latter cases, they are studied as source of active principles but are also exploited to produce marine collagen. In the present work, jellyfish skin polysaccharides (JSP) with glycosaminoglycan (GAG) features were extracted from Rhizostoma pulmo, a main blooming species of Mediterranean Sea, massively augmented by climate leaded “jellyfishication” of the sea. Two main fractions of R. pulmo JSP (RP-JSPs) were isolated and characterized, namely a neutral fraction (RP-JSP1) and a sulphate rich, negatively charged fraction (RP-JSP2). The two fractions have average molecular weights of 121 kDa and 590 kDa, respectively. Their sugar composition was evaluated through LC-MS analysis and the result confirmed the presence of typical GAG saccharides, such as glucose, galactose, glucosamine and galactosamine. Their use as promoters of wound healing was evaluated through in vitro scratch assay on murine fibroblast cell line (BALB/3T3 clone A31) and human keratinocytes (HaCaT). Both RP-JSPs demonstrated an effective confluency rate activity leading to 80% of scratch repair in two days, promoting both cell migration and proliferation. Additionally, RP-JSPs exerted a substantial protection from oxidative stress, resulting in improved viability of treated fibroblasts exposed to H2O2. The isolated GAG-like polysaccharides appear promising as functional component for biomedical skin treatments, as well as for future exploitation as pharmaceutical excipients.
Two Cases of Autoimmune Thyroid Disorders after COVID Vaccination in Dialysis Patients
Authors: Lioulios Georgios , Tsouchnikas Ioannis , Dimitriadis Chrysostomos , Giamalis Panagiotis , Pella Eva , Christodoulou Michalis , Stangou Maria , Papagianni Aikaterini
Published: September 2022

SARS-CoV-2 infection and vaccination have been associated with autoimmune thyroid dysfunctions. Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) and molecular mimicry have been referred to as potential causes. Such a case has not been reported in immunocompromised end-stage renal disease (ESRD) patients. Herein we present two dialysis patients with no previous history of thyroid disease who developed immune mediated thyroid disorders after BNT162b mRNA vaccine against SARS-CoV-2. The first patient is a 29-year-old man on hemodialysis diagnosed with Grave’s disease four months post-vaccination and the second one is a 67-year-old female on peritoneal dialysis who developed Hashimoto’s thyroiditis two months post-vaccination. Grave’s disease is uncommon in dialysis patients, whereas Hashimoto’s thyroiditis has a higher incidence in this population. Time proximity in both cases suggests potential causality. To our knowledge, this is the first report of de novo immune-mediated thyroid disorders in dialysis patients following vaccination against SARS-CoV-2.
Radiofrequency Ablation of Indeterminate Thyroid Nodules: The First North American Comparative Analysis
Authors: Issa Peter P. , Omar Mahmoud , Issa Chad P. , Buti Yusef , Hussein Mohammad , Aboueisha Mohamed , Abdelhady Ali , Shama Mohamed , Lee Grace S. , Toraih Eman , Kandil Emad
Published: September 2022

Thyroid nodules can be classified as benign, malignant, or indeterminate, the latter of which make up 10–30% of nodules. Radiofrequency ablation (RFA) has become an attractive and promising therapy for the treatment of benign thyroid nodules. However, few studies have investigated the safety and efficacy of RFA for the management of indeterminate thyroid nodules. In this study, 178 patients with thyroid nodules diagnosed as benign (Bethesda II) or indeterminate (Bethesda III/IV) by preoperative cytopathological analysis were included. Patients in the benign and indeterminate cohorts had similar thyroid nodule volume reduction rates at 65.60% and 64.20%, respectively (p = 0.68). The two groups had similar nodular regrowth rates, at 11.2% for benign nodules and 9.40% for indeterminate nodules (p = 0.72). A total of three cases of transient dysphonia were reported. RFA of indeterminate thyroid nodules was comparable to that of benign thyroid nodules in all parameters of interest, including volume reduction rate. To our best knowledge, our work is the first North American analysis comparing benign and indeterminate thyroid nodules and suggests RFA to be a promising modality for the management of indeterminate thyroid nodules.
Mechanisms of Kale (Brassica oleracea var. acephala) Tolerance to Individual and Combined Stresses of Drought and Elevated Temperature
Authors: Bauer Nataša , Tkalec Mirta , Major Nikola , Talanga Vasari Ana , Tokić Mirta , Vitko Sandra , Ban Dean , Ban Smiljana Goreta , Salopek-Sondi Branka
Published: September 2022

Rising temperatures and pronounced drought are significantly affecting biodiversity worldwide and reducing yields and quality of Brassica crops. To elucidate the mechanisms of tolerance, 33 kale accessions (B. oleracea var. acephala) were evaluated for individual (osmotic and elevated temperature stress) and combined stress (osmotic + temperature). Using root growth, biomass and proline content as reliable markers, accessions were evaluated for stress responses. Four representatives were selected for further investigation (photosynthetic performance, biochemical markers, sugar content, specialized metabolites, transcription level of transcription factors NAC, HSF, DREB and expression of heat shock proteins HSP70 and HSP90): very sensitive (392), moderately sensitive (395), tolerant (404) and most tolerant (411). Accessions more tolerant to stress conditions were characterized by higher basal content of proline, total sugars, glucosinolates and higher transcription of NAC and DREB. Under all stress conditions, 392 was characterized by a significant decrease in biomass, root growth, photosynthesis performance, fructan content, especially under osmotic and combined stress, a significant increase in HSF transcription and HSP accumulation under temperature stress and a significant decrease in NAC transcription under all stresses. The most tolerant accession under all applied stresses, 411 showed the least changes in all analyzed parameters compared with the other accessions.
Acute Systemic White Blood Cell Changes following Degenerative Cervical Myelopathy (DCM) in a Mouse Model
Authors: Ulndreaj Antigona , Ávila Ariel , Hong James , Zhou Cindy , Fehlings Michael G. , Vidal Pia M.
Published: September 2022

Degenerative cervical myelopathy (DCM) is caused by age-related degeneration of the cervical spine, causing chronic spinal cord compression and inflammation. The aim of this study was to assess whether the natural progression of DCM is accompanied by hematological changes in the white blood cell composition. If so, these changes can be used for diagnosis complementing established imaging approaches and for the development of treatment strategies, since peripheral immunity affects the progression of DCM. Gradual compression of the spinal cord was induced in C57B/L mice at the C5-6 level. The composition of circulating white blood cells was analyzed longitudinally at four time points after induction of DCM using flow cytometry. At 12 weeks, serum cytokine levels were measured using a Luminex x-MAP assay. Neurological impairment in the mouse model was also assessed using the ladder walk test and CatWalk. Stepping function (* p < 0.05) and overground locomotion (*** p < 0.001) were impaired in the DCM group. Importantly, circulating monocytes and T cells were affected primarily at 3 weeks following DCM. T cells were two-fold lower in the DCM group (*** p < 0.0006), whereas monocytes were four-fold increased (*** p < 0.0006) in the DCM compared with the sham group. Our data suggest that changes in white blood cell populations are modest, which is unique to other spinal cord pathologies, and precede the development of neurobehavioral symptoms.
Swim Training Affects on Muscle Lactate Metabolism, Nicotinamide Adenine Dinucleotides Concentration, and the Activity of NADH Shuttle Enzymes in a Mouse Model of Amyotrophic Lateral Sclerosis
Authors: Cieminski Karol , Flis Damian Jozef , Dzik Katarzyna Patrycja , Kaczor Jan Jacek , Wieckowski Mariusz Roman , Antosiewicz Jedrzej , Ziolkowski Wieslaw
Published: September 2022

In this study, we aim to verify whether swim training can improve lactate metabolism, NAD+ and NADH levels, as well as modify the activity of glycolytic and NADH shuttle enzymes and monocarboxylate transporters (MCTs) in skeletal muscle of amyotrophic lateral sclerosis (ALS) mice. ALS mice (SOD1G93A) (n = 7 per group) were analyzed before the onset of ALS, at first disease symptoms (trained and untrained), and the last stage of disease (trained and untrained), and then compared with a wild-type (WT) group of mice. The blood lactate and the skeletal muscle concentration of lactate, NAD+ and NADH, MCT1 and MCT4 protein levels, as well as lactate dehydrogenase (LDH) and malate dehydrogenase (MDH) activities in skeletal muscle were determined by fluorometric, Western blotting, liquid chromatography-MS3 spectrometry, and spectrometric methods. In the untrained terminal ALS group, there were decreased blood lactate levels (p < 0.001) and increased skeletal muscle lactate levels (p < 0.05) as compared with a WT group of mice. The amount of nicotinamide adenine dinucleotides in the ALS groups were also significantly reduced as well as LDH activity and the level of MCT1. Swim training increased lactate levels in the blood (p < 0.05 vs. ALS TERMINAL untrained). In addition, cytosolic MDH activity and the cMDH/LDH 2.1 ratio were significantly higher in trained vs. untrained mice (p < 0.05). The data indicate significant dysfunction of lactate metabolism in ALS mice, associated with a reduction in muscle anaerobic metabolism and NADH transporting enzymes, as well as swim-induced compensation of energy demands in the ALS mice.
Genotype and Phenotype Differences in CADASIL from an Asian Perspective
Authors: Kim Yerim , Bae Jong Seok , Lee Ju-Young , Song Hong Ki , Lee Ju-Hun , Lee Minwoo , Kim Chulho , Lee Sang-Hwa
Published: September 2022

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebral small-vessel disease caused by mutations in the NOTCH3 gene. Classical pathogenic mechanisms are associated with cysteine gain or loss, but recent studies suggest that cysteine-sparing mutations might have a potential role as a pathogen. In comparison with CADASIL patients in Western countries, there are several differences in Asian patients: (1) prevalent locus of NOTCH3 mutations (exons 2–6 [particularly exon 4] vs. exon 11), (2) age at symptom onset, (3) prevalence of cerebral microbleeds and hemorrhagic stroke, (4) clinical symptoms, and (5) severity of white matter hyperintensities and typical involvement of the anterior temporal pole in magnetic resonance imaging. Both ethnicity and founder effects contribute to these differences in the clinical NOTCH3 spectrum in different cohorts. More functional investigations from diverse races are needed to clarify unknown but novel variants of NOTCH3 mutations. This review may broaden the spectrum of NOTCH3 variants from an Asian perspective and draw attention to the hidden pathogenic roles of NOTCH3 variants.
The Potential Roles of Extracellular Vesicles as Biomarkers for Parkinson’s Disease: A Systematic Review
Authors: Valencia Jessica , Ferreira Marta , Merino-Torres J. Francisco , Marcilla Antonio , Soriano Jose M.
Published: September 2022

Parkinson’s disease (PD) is a slowly progressive neurodegenerative disorder, characterized by the misfolding and aggregation of α-synuclein (α-syn) into Lewy bodies and the degeneration of dopaminergic neurons in the substantia nigra pars compacta. The urge for an early diagnosis biomarker comes from the fact that clinical manifestations of PD are estimated to appear once the substantia nigra has deteriorated and there has been a reduction of the dopamine levels from the striatum. Nowadays, extracellular vesicles (EVs) play an important role in the pathogenesis of neuro-degenerative diseases as PD. A systematic review dated August 2022 was carried out with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses with the aim to analyze the potential role of EVs as biomarkers for PD. From a total of 610 articles retrieved, 29 were eligible. This review discusses the role of EVs biochemistry and their cargo proteins, such as α-syn and DJ-1 among others, detected by a proteomic analysis as well as miRNAs and lncRNAs, as potential biomarkers that can be used to create standardized protocols for early PD diagnosis as well as to evaluate disease severity and progression.
Therapeutic Potential of Mesenchymal Stem Cell-Secreted Factors on Delay in Corneal Wound Healing by Nitrogen Mustard
Authors: An Seungwon , Shen Xiang , Anwar Khandaker , Ashraf Mohammadjavad , Lee Hyungjo , Koganti Raghuram , Ghassemi Mahmood , Djalilian Ali R.
Published: September 2022

Ocular surface exposure to nitrogen mustard (NM) leads to severe ocular toxicity which includes the separation of epithelial and stromal layers, loss of endothelial cells, cell death, and severe loss of tissue function. No definitive treatment for mustard gas-induced ocular surface disorders is currently available. The research was conducted to investigate the therapeutic potential of mesenchymal stem cell-conditioned media (MSC-CM) in NM-induced corneal wounds. NM was added to different types of corneal cells, the ocular surface of porcine, and the ocular surface of mice, followed by MSC-CM treatment. NM significantly induced apoptotic cell death, cellular ROS (Reactive oxygen species), and reduced cell viability, metabolic gene expression, and mitochondrial function, and, in turn, delayed wound healing. The application of MSC-CM post NM exposure partially restored mitochondrial function and decreased intracellular ROS generation which promoted cell survival. MSC-CM therapy enhanced wound healing process. MSC-CM inhibited NM-induced apoptotic cell death in murine and porcine corneal tissue. The application of MSC-CM following a chemical insult led to significant improvements in the preservation of corneal structure and wound healing. In vitro, ex vivo, and in vivo results suggest that MSC-CM can potentially provide targeted therapy for the treatment of chemical eye injuries, including mustard gas keratopathy (MGK) which presents with significant loss of vision alongside numerous corneal pathologies.
Chemonastic Stalked Glands in the Carnivorous Rainbow Plant Byblis gigantea LINDL. (Byblidaceae, Lamiales)
Authors: Poppinga Simon , Knorr Noah , Ruppert Sebastian , Speck Thomas
Published: September 2022

Carnivorous rainbow plants (Byblis, Byblidaceae, Lamiales) possess sticky flypaper traps for the capture, retention, and digestion of prey (mainly small insects). The trapping system is based on a multitude of millimeter-sized glandular trichomes (also termed stalked glands), which produce adhesive glue drops. For over a century, the trapping system of Byblis was considered passive, meaning that no plant movement is involved. Recently, a remarkable discovery was made: the stalked glands of Byblis are indeed capable of reacting to chemical (protein) stimuli with slow movement responses. This prompted us to investigate this phenomenon further with a series of experiments on the stimulation, kinematics, actuation, and functional morphology of the stalked glands of cultivated Byblis gigantea plants. Measured stalked gland lengths and densities on the trap leaves are similar to the data from the literature. Motion reactions could only be triggered with chemical stimuli, corroborating the prior study on the stalked gland sensitivity. Reaction time (i.e., time from stimulation until the onset of motion) and movement duration are temperature-dependent, which hints towards a tight physiological control of the involved processes. The stalked gland movement, which consist of a sequence of twisting and kinking motions, is rendered possible by the components of the stalk cell wall and is furthermore anatomically and mechanically predetermined by the orientation of cellulose microfibrils in the cell wall. Successive water displacement processes from the stalk cell into the basal cells actuate the movement. The same kinematics could be observed in stalked glands drying in air or submersed in a saturated salt solution. Stimulated and dried stalked glands as well as those from the hypertonic medium were capable of regaining their initial shape by rehydration in water. However, no glue production could be observed afterwards. The long-time overlooked chemonastic movements of stalked glands may help Byblis to retain and digest its prey; however, further research is needed to shed light on the ecological characteristics of the rainbow plant’s trapping system.
D121 Located within the DRY Motif of P2Y12 Is Essential for P2Y12-Mediated Platelet Function
Authors: Dangelmaier Carol , Mauri Benjamin , Patel Akruti , Kunapuli Satya P. , Kostyak John C
Published: September 2022

Platelets are anucleate cells that mediate hemostasis. This occurs via a primary signal that is reinforced by secreted products such as ADP that bind purinergic receptors (P2Y1 and P2Y12) on the platelet surface. We recently identified a human subject, whom we termed platelet defect subject 25 (PDS25) with a platelet functional disorder associated with the P2Y12 receptor. PDS25 has normal blood cell counts and no history of bleeding diathesis. However, platelets from PDS25 have virtually no response to 2-MeSADP (a stable analogue of ADP). Genetic analysis of P2Y12 from PDS25 revealed a heterozygous mutation of D121N within the DRY motif. Rap1b activity was reduced in platelets from PDS25, while VASP phosphorylation was enhanced, suggesting that signaling from the P2Y12 receptor was interrupted by the heterozygous mutation. To explore this further, we produced knock-in mice that mimic our subject. Bleeding failed to cease in homozygous KI mice during tail bleeding assays, while tail bleeding times did not differ between WT and heterozygous KI mice. Furthermore, occlusions failed to form in most homozygous KI mice following carotid artery injury via FeCl3. These data indicate that the aspartic acid residue found in the DRY motif of P2Y12 is essential for P2Y12 function.
Therapeutic Advances in Immunotherapies for Hematological Malignancies
Authors: Nogami Ayako , Sasaki Koji
Published: September 2022

Following the success of immunotherapies such as chimeric antigen receptor transgenic T-cell (CAR-T) therapy, bispecific T-cell engager therapy, and immune checkpoint inhibitors in the treatment of hematologic malignancies, further studies are underway to improve the efficacy of these immunotherapies and to reduce the complications associated with their use in combination with other immune checkpoint inhibitors and conventional chemotherapy. Studies of novel therapeutic strategies such as bispecific (tandem or dual) CAR-T, bispecific killer cell engager, trispecific killer cell engager, and dual affinity retargeting therapies are also underway. Because of these studies and the discovery of novel immunotherapeutic target molecules, the use of immunotherapy for diseases initially thought to be less promising to treat with this treatment method, such as acute myeloid leukemia and T-cell hematologic tumors, has become a reality. Thus, in this coming era of new transplantation- and chemotherapy-free treatment strategies, it is imperative for both scientists and clinicians to understand the molecular immunity of hematologic malignancies. In this review, we focus on the remarkable development of immunotherapies that could change the prognosis of hematologic diseases. We also review the molecular mechanisms, development processes, clinical efficacies, and problems of new agents.