bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estrategias de puesta en valor turístico de las lagunas y cascadas de la región Lambayeque-Perú
Authors: Rodríguez-Serquén Segundo Arturo 
Published: February 2023

En la presente investigación se encontraron estrategias de puesta en valor turístico de las lagunas y cascadas que poseen las comunidades de Laquipampa (Incahuasi), Mayascón (Pítipo), El Espinal (Oyotún) ubicadas en la Región Lambayeque-Perú, atractivos naturales de los más cotizados por el turista moderno, con la finalidad de integrarlas al circuito turístico nacional y viabilizar a través del turismo el desarrollo socio-económico de las comunidades mencionadas. Ello se logró después de registrar la oferta turística existente y potencial e identificar las necesidades prioritarias en materia de servicios básicos, infraestructura y recursos humanos requeridos por el turista. La investigación tuvo un enfoque cualitativo, de corte transversal, descriptivo y exploratorio; el método de investigación empleado fue del tipo inductivo. Se empezó efectuando una amplia indagación bibliográfica, visitas de campo y practicando entrevistas y cuestionarios acerca de la oferta turística y la infraestructura existente. Luego se analizó y ejecutó un diagnóstico con la información para finalmente plantear estrategias de marketing, de gestión de inversión pública y privada, de capacitación turística y de desarrollo sostenible para la puesta en valor de los valiosos recursos naturales de las comunidades. Las estrategias encontradas posibilitarán el desarrollo de las comunidades rurales empobrecidas del país objeto de estudio, dueñas de ricos escenarios naturales, valores culturales ancestrales y también importantes lugares arqueológicos.
DEVELOPMENT OF THE STRUCTURE OF AN AUTOMATED SYSTEM FOR DIAGNOSING DISEASES
Authors: Myrzakerimova Alua , Kolesnikova Katerina , Nurmaganbetova Mugulsum 
Published: February 2023

Today, the importance of information support for various medical technologies has increased significantly. The use of modern information technologies is becoming a critical factor in the development of most branches of knowledge and areas of practice, so the development and implementation of information systems is an urgent task. The clinical decision support system provides clinicians and stakeholders with individualized patient assessments and recommendations to assist in the clinical decision-making process.
Knowledge-based information systems are widely used in medicine around the world. Modern technical capabilities make it possible to reach a qualitatively new level of presentation of the course of the disease, namely, based on appropriate mathematical models, to model the typical development of the pathological process in a particular disease, to speed up the process of diagnosing and receiving recommendations on treatment protocols.
In Kazakhstan, there is no variety of decision support systems in medicine, especially in the process of diagnosing diseases. The purpose of this study is to develop the structure of an automated system for diagnosing diseases. The Unified Modeling Language (UML) is used as a design tool. The structure of the automated system is presented; the main components and key terms are considered. A mathematical model of diagnostics is shown (in the example of diseases of intestinal and pancreatic insufficiency) based on decision-making methods with fuzzy initial data. A diagram of the data flows of the system is presented. Thus, the paper proposes the structure of an automated system that will contribute to high-quality diagnostics due to an effective method of system organization and the use of fuzzy set theory methods.
Assessment of Quality of the Electronic Education System in the Corona Crisis Period: Applied Study on Al al-Bayt University
Authors: Alsharafat Wafa , Alrashdan Wesam Kurdi , Munther Omar , Yamman Mohammad , Khalid Amaar 
Published: February 2023

In response to the coronavirus crisis, higher education institutions have partially or fully transformed into electronic education systems (EESs). This paper presents the results of a student survey conducted at AL al-Bayt University to assess the quality of the electronic educational system (EES) during the coronavirus pandemic. The study variables addressed by the questionnaire were tangible physical features (TPFs), flexibility (FEES), examination construction and management (ECM); admission, storage, and registration management (ASRM), security and privacy (S&P), learning site content (LSC); and students’ level of satisfaction (LoS). The exploratory study methodology was applied to 324 students at AABU, where the research data were collected using a Google Docs questionnaire and distributed to students. The results highlighted that students were satisfied with the quality of EES implemented by AABU during the lockdown period in terms of tangible physical features (TPF) and learning site content (LSC) and there was a statistically significant relationship between TPF and LSC. However, some undesirable features were reported, such as a lack of adequate infrastructure for students, which enabled them to interact effectively with their teachers to gain the target of applying EES. Consequently, AABU needs to implement effective measures to improve and increase the quality and level of satisfaction with EES. Finally, electronic education is a more adapted, smooth, and affordable alternative than traditional face-to-face education.
Gut microbiota modulate susceptibility to bleomycin-induced lung injury.
Authors: Yoon Young me , Barrón Gabe M , Hrusch Cara L , Fei Na , Leone Vanessa A , Sperling Anne I 
Published: February 2023

Abstract
Acute lung injury (ALI) resulting in acute respiratory distress syndrome (ARDS) affects almost 200,000 people in the US each year, leading to 75,000 deaths. Airway instillation of bleomycin (BLM) in mice is a widely used, yet challenging model for ALI due to high variability. We have observed that B6 mice from two SPF facilities at our University exhibit significantly different mortality and weight loss in response to BLM. To test whether the facility-dependent response to BLM can be transferred by the microbiome, we conventionalized germ-free (GF) B6 littermates in each facility and challenged with BLM. Conventionalized GF mice recapitulated the respective donors’ response to BLM. Further, fecal microbiota transfer from the facility where the mice had worse mortality into the mice in the facility with more survival rendered recipient mice more susceptible to BLM compared to controls, indicating that the differential gut microbiome between two facilities were sufficient to modulate BLM response. To identify microorganisms that drive the phenotype, we compared gut microbial community memberships by 16S rRNA and metagenomics sequencing. Interestingly, BLM highly susceptible mice had greater alpha diversity and harbored specific species of Bacteroides, Prevotella, and Helicobacter genera. Flow cytometry of the lung immune cell landscape at baseline revealed comparable composition and phenotype of adaptive immune cells regardless of facility. However, lung NK cells were significantly increased BLM highly susceptible mice. Thus, we demonstrate that distinct gut microbiota communities modulate death and weight loss in response to BLM-induced lung injury, implicating host-commensal interactions in regulating ALI outcomes.
Consequences of maternal breast milk antibodies on neonatal mucosal immunity and intestinal microbe composition
Authors: Wang Bingjie , Koch Meghan 
Published: February 2023

Abstract
Breastfeeding is associated with decreased risk of acquiring inflammatory bowel disorders later in life. As breastfeeding is not possible for all mothers and children, having a mechanistic understanding of this process can lead to the development of early-life interventions to foster beneficial host-microbiota relationships, particularly in neonates who are not breastfed.
We have shown that mice lacking breast milk antibodies (bmAbs) exhibit dysregulated intestinal homeostasis. These mice harbor increased numbers of live bacteria in the mesenteric lymph nodes and exhibit perturbations in mucosal immunity, including elevated T follicular helper (Tfh) cell and germinal center (GC) B cell responses in the gut-associated lymphoid tissues. Antibodies are key regulators of host-microbiome interactions, and T-dependent (TD) GC derived B cells can persist up to the lifetime of the host. We hypothesize that the TD antibodies generated by the neonate in the absence of bmAbs target resident gut bacteria and lead to long-term alterations in the composition of the microbiota.
We performed RT-PCR of the bacterial 16s rRNA gene to quantify the amount of wall-associated microbes in the small and large intestine of mice that received or did not receive bmAbs. To probe the effects of Tfh cells and TD antibodies, we treated half of the mice from each group with anti-ICOS ligand antibody, which blocks Tfh and GC cell formation. We found no significant difference in bacterial burden across all four groups in the small or large intestine. These data suggest that Tfh-cell dependent, bmAb-dependent antibodies do not alter the abundance of wall-associated microbes. Studies are ongoing to determine if bmAbs affect intestinal microbe composition later in life.
Tissue localization and virus specificity shape the maintenance and function of human virus-specific memory T cells recognizing HCMV and influenza A
Authors: Poon Maya M.L. , Byington Eve , Meng Wenzhao , Dogra Pranay , Lam Nora , Szabo Peter Anthony , Ural Basak , Grifoni Alba , Weiskopf Daniela , Kubota Masaru , Matsumoto Rei , Sette Alessandro , Shen Yufeng , Prak Eline T Luning , Farber Donna L 
Published: February 2023

Abstract
Generation and maintenance of memory T cells within tissue sites of infection is critical for long-term antiviral protection. Current knowledge of human antiviral responses is largely derived from studies sampling peripheral blood. Yet, little is known about human tissue-localized antiviral immunity. Utilizing our human donor tissue resource established in collaboration with LiveOnNY, we investigated how tissue, virus, and age shape T cell maintenance across diverse tissues and their function when presented with antigens derived from human cytomegalovirus (HCMV) or influenza A virus (flu). Using flow cytometry, we show that virus-specific CD8 T cells are maintained in diverse tissues with subset differentiation and distribution shaped by virus specificity and age. Compared to T cells recognizing HCMV, flu-specific T cells display higher levels of residency markers—CD69 and CD103—particularly in adult compared to pediatric donors. In contrast, HCMV-specific T cells are maintained in greater abundance as terminally-differentiated effector T cells. Sequencing of the T cell receptor CDR3b chain reveals that, while both HCMV- and flu-specific T cells demonstrate clonal overlap across multiple tissues, HCMV-specific T cells display greater clonality and less diversity. When presented with viral antigens, HCMV- and flu-specific T cells are polyfunctional. Additionally, single-cell transcriptome profiling reveals tissue localization is the primary determinant of antigen-driven responses. Together, these studies demonstrate the dynamics of T cell differentiation and maintenance throughout the human body, which is primarily driven by virus specificity, and the role of tissue localization in shaping antiviral response.
Identifying mechanisms that enhance the longevity of tissue-resident memory CD8+ T cells in the lung
Authors: Lobby Jenna L , Uddback Ida Elin Maria , Scharer Christopher D. , Mi Tian , Boss Jeremy M. , Thomsen Allan R , Christensen Jan Pravsgaard , Kohlmeier Jacob E 
Published: February 2023

Abstract
Lung tissue-resident memory CD8+ T cells (TRM) are crucial mediators of cellular immunity against influenza viruses, but the number of these cells in the lung tissue gradually declines in the months following influenza infection. Recently, we showed that intranasal immunization with a replication-deficient adenovirus that expresses the nucleoprotein from influenza A virus (AdNP) results in long-term maintenance of lung CD8+ TRM for up to 1-year post-immunization. However, the mechanism(s) that promote this enhanced longevity of FluNP-specific CD8+ lung TRM remain unknown. Using a combination of mouse infection models, flow cytometry, and RNA-sequencing, we compared CD8+ T cells from the airways, lungs, and spleen of AdNP-immunized or influenza x31-infected mice. We found that CD8+ TRM in the lungs of AdNP-immunized mice show increased homeostatic turnover and hallmarks of persistent antigen stimulation in the lung. However, RNA-sequencing analysis comparing lung CD8+ TRM from AdNP-immunized and x31-infected mice at 1-month and 1-year post-immunization showed only minor variations that did not fully explain the differences in lung TRM persistence. Lineage tracing experiments using a Cre recombinase-expressing Adenovirus (AdCre) identified alveolar macrophages as the primary cell type harboring persistent antigen in the lung. Together, these results define one mechanism for enhancing the durability of lung TRM, which is an important consideration for the design of future cell-mediated influenza vaccines
T cell cross-reactivity during heterologous infection results in immunodomination and enhanced cytolytic capacity at the expense of virus-specific responses
Authors: Hassert Mariah , Brien James D , Pinto Amelia K 
Published: February 2023

Abstract
Flaviviruses constitute a genus of closely related arthropod-borne viruses including Zika virus, the four serotypes of dengue virus, and yellow fever virus, which circulate in the same geographic regions. These viruses share a substantial degree of genetic similarity and consequently, antigenic overlap has been reported by evaluating T cell and antibody responses in humans, non-human primates, and mice. However, it has not been determined how existing immunity to a heterologous flavivirus impacts functional immune responses to virus-specific and cross-reactive epitopes. We hypothesize that cross-reactive T cells from prior flavivirus exposures will expand robustly during a heterologous challenge and that these cells primed during a heterologous infection will be functionally different from cells of the same specificity primed during a homologous infection. Using various mouse models of flavivirus infection, we have identified a pan-flavivirus reactive CD8+ T cell epitope. We show in a heterologous infection model in which dengue virus exposure precedes Zika virus infection, T cell responses to the cross-reactive epitope dominate at the expense of the Zika-specific T cell responses. These cross-reactive T cells display enhanced killing capacity, in addition to other functional changes. The culmination of these features drive altered protective capacity when compared to homologously primed T cells in our mouse model of Zika infection. Our findings provide a mechanistic understanding of cross-reactive T cell control during heterologous infection and have important implications for vaccine design, as these results define the functional consequences of priming a cross-reactive T cell response for a pan-flavivirus vaccine.
High levels of endemic coronaviruses reactive CD4+ T cells in SARS-CoV-2 seronegative health care workers
Authors: Antunes Ricardo Filipe da Silva , Pallikkuth Suresh , Williams Erin , Yu Esther Dawen , Mateus Jose , Quiambao Lorenzo , Wang Eric , Rawlings Stephen , Stadlbauer Daniel , Jiang Kaijun , Amanat Fatima , Arnold David , Andrews David , Fuego Irma , Dan Jennifer , Grifoni Alba , Weiskopf Daniela , Krammer Florian , Crotty Shane , Hoffer Michael , Pahwa Savita , Sette Alessandro 
Published: February 2023

Abstract
Healthcare workers (HCW) due to occupational exposure to patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as a population at risk during the current coronavirus disease-2019 (COVID-19) pandemic. Pre-existing immunity induced by the exposition to several pathogens, including respiratory viruses, can shape susceptibility to infections but little is known about the presence of cross-reactive memory T cells that have the potential to recognize SARS-CoV-2. Herein we measured CD4+ T cell responses against common cold corona (CCC) viruses and SARS-CoV-2 in high-risk health care workers (HCW) and community controls. We observed higher levels of CCC reactive T cells in SARS-CoV-2 seronegative HCW compared to community donors, consistent with potential higher occupational exposure of HCW to CCC. We further show that SARS-CoV-2 reactivity of seronegative HCW was higher than community controls and correlation between CCC and SARS-CoV-2 responses shown to be consistent with cross-reactivity and not associated with recent in vivo activation. Surprisingly, CCC reactivity was consistently decreased in SARS-CoV-2 infected HCW, suggesting that exposure to SARS-CoV-2 might interfere with CCC responses, either directly or indirectly. This result was unexpected, but consistently detected in independent cohorts derived from Miami and San Diego.
Human herpesvirus diversity is altered in predicted HLA class I binding peptides
Authors: Palmer William H , Norman Paul J 
Published: February 2023

Abstract
Human Leukocyte Antigen (HLA) Class I molecules present intracellularly derived peptide fragments for discrimination of self from non-self, thereby alerting the adaptive immune response to infecting pathogens. Among these pathogens are herpesviruses, including Epstein-Barr virus (EBV), which are large DNA viruses that have coevolved with humans. Previous analyses suggest that natural selection pressures imposed by HLA recognition may affect herpesvirus genetic diversity, especially for proteins involved in the establishment of latency. Because HLA allele frequencies are highly differentiated across human populations, we tested the hypothesis that herpesvirus latency genes have also become differentiated across human populations through adaptation to the local HLA environment. We predicted the protein regions most likely to be recognized by HLA in EBV, Human cytomegalovirus (HCMV), and Varicella-zoster virus (VZV) strains from &gt;15 representative human populations. We compared sequence diversity and population differentiation in HLA-binding and non-binding regions of lytic and latent herpesvirus proteins. We observed increased population differentiation in herpesvirus latent proteins, specifically in regions targeted by HLA. Whereas HLA recognizes conserved peptides in most viral proteins, this pattern was reversed in HLA binding sites of EBV and HCMV proteins expressed in latency. We also predicted fewer HLA-binding latent EBV peptides from higher frequency HLA alleles, consistent with EBV adapting away from HLA recognition. Together, these results suggest that EBV and HCMV diversity is altered in regions recognized by HLA, perhaps due to population-specific natural selection by local HLA alleles.
HLA allele frequencies and susceptibility analysis in 94 Florida residents with COVID-19 disease
Authors: Shen Yiran , Nguyen Cuong Q , Ostrov David A 
Published: February 2023

Abstract
COVID-19 is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) of suspected zoonotic origin. Although coronaviruses (CoVs) are relatively common across species, mutations can cause severe symptoms in humans. The widespread clinical symptoms encompass a large group of asymptomatic COVID-19 patients, raising a crucial question regarding genetic susceptibility, i.e. whether human leukocyte antigens (HLA) play a role in the patient symptomology. In this study, we hypothesize that “A certain HLA allele or combination of certain alleles can serve as biomarker for the severity of COVID-19”. To test this hypothesis, we genotyped HLAs of 94 patients with confirmed COVID-19 and 89 healthy individuals in Florida, USA, we found certain alleles (HLA-A*74:01, -A*30:01, DPA1*03:01, DPB1*01:01, and DQA1*05:01) were associated with disease susceptibility and some alleles (HLA-DPA1*01:03, DPB1*11:01 and DQA1*02:01) were associated with protection. Furthermore, using in-silico HLA docking modeling, we found that DPA1*01:03 is associated with reduced SARS-CoV-2 infectivity by binding to SARS-CoV-2 spike peptide with high affinity. Also, polymorphism in the antigen binding cleft of HLA-DP has the potential to inhibit binding to peptides derived from SARS-CoV-2 spike protein. The results provided a broader understanding of the genetic HLA association pertaining to the severity of COVID-19. Additionally, the results indicted the importance in performing the HLA genotyping with virus detection to identify high risk individuals.
An early decline in circulating lymphoid progenitors contributes to the age-associated reduction in ETP numbers
Authors: Srinivasan Jayashree , Vasudev Anusha , Selden Hilary J. , Encarnacion Perez Jr. , LaFleur Bonnie , Sinari Shripad , Krueger Andreas , Richie Ellen R. , Ehrlich Lauren I. 
Published: February 2023

Abstract
Age-associated thymic involution is characterized by the decreased generation and export of T cells from the thymus, which in turn, is associated with increased susceptibility to infections. Elucidating the cause of thymic involution will inform strategies to restore thymopoiesis with age. T cells develop from thymus seeding progenitors that migrate from the bone marrow (BM) to the thymus. Early T-cell progenitors (ETPs) require signals from the thymic microenvironment to undergo T-lineage commitment and differentiation. In mice, we find that there is a significant decline in thymocyte cellularity as early as 3 months of age (3MO), which is mirrored by a striking reduction in ETPs. This early thymic involution could be driven by changes in hematopoietic progenitors and/or thymic stromal cells. Using a multicongenic BM transplantation approach, we determined that the number of ETP-supportive niches does not diminish with age. However, modulating the thymic stromal compartment sustains ETP cellularity, suggesting that age-associated defects in ETP niche quality may contribute to ETP decline. Notably, the number of lymphoid progenitors in the BM and blood declines dramatically by 3MO, although their cell-intrinsic capacity to seed and differentiate in the thymus is unimpaired. Together, our findings suggest that the early decline in ETP numbers is due to both hematopoietic and stromal age-associated changes.
This work was supported by P01 AG052359 from the NIH-National Institute of Aging.