bluuebunny/crossref_metadata_2025_split huggingface dataset:
E6020, a TLR4 Agonist Adjuvant, Enhances Both Antibody Titers and Isotype Switching in Response to Immunization with Hapten-Protein Antigens and Is Diminished in Mice with TLR4 Signaling Insufficiency
Authors: Gopalakrishnan Archana , Richard Katharina , Wahid Rezwanul , Harley Regina , Sztein Marcelo B , Hawkins Lynn D , Vogel Stefanie N 
Published: January 2023

Abstract
The mechanisms by which TLR4-based adjuvants enhance immunogenicity are not fully understood. We have taken advantage of a novel knock-in mouse strain that homozygously expresses two single-nucleotide polymorphisms (SNPs) that are homologous to human TLR4 (rs4986790 and rs4986791) and have been associated with LPS hyporesponsiveness in vivo and in vitro. TLR4-SNP (coexpressing mutations D298G/N397I in TLR4) mice that recapitulate the human phenotype were compared with wild-type (WT) mice for their hapten-specific Ab responses after immunization with hapten 4-hydroxy-3-nitrophenyl acetyl (NP) NP-Ficoll or NP-OVA in the absence or presence of a water-soluble TLR4 analog adjuvant, E6020. IgM and IgG anti-NP responses were comparable in WT and TLR4-SNP mice after immunization with either NP-Ficoll or NP-OVA only. E6020 significantly yet transiently improved the IgM and IgG anti-NP responses of both WT and TLR4-SNP mice to NP-Ficoll (T-independent), with modestly enhanced Ab production in WT mice. In contrast, T-dependent (NP-OVA), adjuvant-enhanced responses showed sustained elevation of NP-specific Ab titers in WT mice, intermediate responses in TLR4-SNP mice, and negligible enhancement in TLR4−/− mice. E6020-enhanced early humoral responses in WT and TLR4-SNP mice to NP-OVA favored an IgG1 response. After a second immunization, however, the immune responses of TLR4-SNP mice remained IgG1 dominant, whereas WT mice reimmunized with NP-OVA and E6020 exhibited increased anti-NP IgG2c titers and a sustained increase in the IgG1 and IgG2c production by splenocytes. These findings indicate that E6020 increases and sustains Ab titers and promotes isotype class switching, as evidenced by reduced titers and IgG1-dominant immune responses in mice with TLR4 insufficiency.
The Impact of Helminth Coinfection on Innate and Adaptive Immune Resistance and Disease Tolerance during Toxoplasmosis
Authors: Rovira-Diaz Eliezer , El-Naccache Darine W , Reyes Jojo , Zhao Yanlin , Nasuhidehnavi Azadeh , Chen Fei , Gause William C , Yap George S 
Published: January 2023

Abstract
More than 2 billion people worldwide are infected with helminths. Thus, it is possible for individuals to experience concomitant infection with helminth and intracellular microbes. Although the helminth-induced type 2 response can suppress type 1 proinflammatory responses required for the immunity against intracellular pathogens in the context of a coinfection, conflicting evidence suggest that helminth infection can enhance antimicrobial immunity. Using a coinfection model with the intestinal helminth Heligmosomoides polygyrus followed by infection with Toxoplasma gondii in Mus Musculus, we showed that the complex and dynamic effect of helminth infection is highly suppressive during the innate phase (days 0–3) of T. gondii infection and less stringent during the acute phase (d10). Helminth coinfection had a strong suppressive effect on the neutrophil, monocytic, and early IFN-γ/IL-12 responses. The IFN-γ response was later restored by compensatory production from T cells despite decreased effector differentiation of T. gondii–specific CD8 T cells. In accordance with the attenuated IFN-γ response, parasite loads were elevated during the acute phase (d10) of T. gondii infection but were transiently controlled by the compensatory T cell response. Unexpectedly, 40% of helminth-coinfected mice exhibited a sustained weight loss phenotype during the postacute phase (d14–18) that was not associated with T. gondii outgrowth, indicating that coinfection led to decreased disease tolerance during T. gondii infection. Our work uncovers the dynamic nature of the helminth immunomodulatory effects on concomitant infections or immune responses and unveils a loss of disease tolerance phenotype triggered by coinfection with intestinal helminth.
Cutting Edge: CCR9 Promotes CD8+ T Cell Recruitment to the Brain during Congenital Cytomegalovirus Infection
Authors: Hilt Zachary T , Charles Wisler , Cheng Katarina E , Tabilas Cybelle , Steinhilber Megan , Wesnak Samantha P , Smith Norah L , Schaffer Chris B , Rudd Brian D 
Published: January 2023

Abstract
CD8+ T lymphocytes infiltrate the brain during congenital CMV infection and promote viral clearance. However, the mechanisms by which CD8+ T cells are recruited to the brain remain unclear. Using a mouse model of congenital CMV, we found a gut-homing chemokine receptor (CCR9) was preferentially expressed in CD8+ T cells localized in the brain postinfection. In the absence of CCR9 or CCL25 (CCR9’s ligand) expression, CD8+ T cells failed to migrate to key sites of infection in the brain and protect the host from severe forms of disease. Interestingly, we found that expression of CCR9 on CD8+ T cells was also responsible for spatial temporal positioning of T cells in the brain. Collectively, our data demonstrate that the CMV-infected brain uses a similar mechanism for CD8+ T cell homing as the small intestine.
G307S DNAM-1 Mutation Exacerbates Autoimmune Encephalomyelitis via Enhancing CD4+ T Cell Activation
Authors: Murata Rikito , Kinoshita Shota , Matsuda Kenshiro , Kawaguchi Atsushi , Shibuya Akira , Shibuya Kazuko 
Published: January 2023

Abstract
Although rs763361, which causes a nonsynonymous glycine-to-serine mutation at residue 307 (G307S mutation) of the DNAX accessory molecule-1 (DNAM-1) immunoreceptor, is a single-nucleotide polymorphism associated with autoimmune disease susceptibility, little is known about how the single-nucleotide polymorphism is involved in pathogenesis. In this study, we established human CD4+ T cell transfectants stably expressing wild-type (WT) or G307S DNAM-1 and showed that the costimulatory signal from G307S DNAM-1 induced greater proinflammatory cytokine production and cell proliferation than that from wild-type DNAM-1. The G307S mutation also enhanced the recruitment of the tyrosine kinase Lck and augmented p-Tyr322 of DNAM-1. We also established a mouse myelin Ag–specific CD4+ T cell transfectant stably expressing the chimeric DNAM-1 (chDNAM-1) consisting of the extracellular, transmembrane, and a part of intracellular regions of mouse DNAM-1 (residues 1–285) fused with the part of the intracellular region (residues 286–336) of human WT or G307S chDNAM-1. Adoptive transfer of the mouse T cell transfectant expressing the G307S chDNAM-1 into mice exacerbated experimental autoimmune encephalomyelitis compared with the transfer of cells expressing the WT chDNAM-1. These findings suggest that rs763361 is a gain-of-function mutation that enhances DNAM-1–mediated costimulatory signaling for proinflammatory responses.
Diversity in Cortical Thymic Epithelial Cells Occurs through Loss of a Foxn1-Dependent Gene Signature Driven by Stage-Specific Thymocyte Cross-Talk
Authors: White Andrea J , Parnell Sonia M , Handel Adam , Maio Stefano , Bacon Andrea , Cosway Emilie J , Lucas Beth , James Kieran D , Cowan Jennifer E , Jenkinson William E , Hollander Georg A , Anderson Graham 
Published: January 2023

Abstract
In the thymus, cortical thymic epithelial cells (cTECs) and medullary thymic epithelial cells support αβT cell development from lymphoid progenitors. For cTECs, expression of a specialized gene signature that includes Cxcl12, Dll4, and Psmb11 enables the cortex to support T lineage commitment and the generation and selection of CD4+CD8+ thymocytes. Although the importance of cTECs in T cell development is well defined, mechanisms that shape the cTEC compartment and regulate its functional specialization are unclear. Using a Cxcl12DsRed reporter mouse model, we show that changes in Cxcl12 expression reveal a developmentally regulated program of cTEC heterogeneity. Although cTECs are uniformly Cxcl12DsRed+ during neonatal stages, progression through postnatal life triggers the appearance of Cxcl12DsRed− cTECs that continue to reside in the cortex alongside their Cxcl12DsRed+ counterparts. This appearance of Cxcl12DsRed− cTECs is controlled by maturation of CD4−CD8−, but not CD4+CD8+, thymocytes, demonstrating that stage-specific thymocyte cross-talk controls cTEC heterogeneity. Importantly, although fate-mapping experiments show both Cxcl12DsRed+ and Cxcl12DsRed− cTECs share a common Foxn1+ cell origin, RNA sequencing analysis shows Cxcl12DsRed− cTECs no longer express Foxn1, which results in loss of the FOXN1-dependent cTEC gene signature and may explain the reduced capacity of Cxcl12DsRed− cTECs for thymocyte interactions. In summary, our study shows that shaping of the cTEC compartment during the life course occurs via stage-specific thymocyte cross-talk, which drives loss of Foxn1 expression and its key target genes, which may then determine the functional competence of the thymic cortex.
HLA Class I Supertype Classification Based on Structural Similarity
Authors: Shen Yue , Parks Jerry M , Smith Jeremy C 
Published: January 2023

Abstract
HLA class I proteins, a critical component in adaptive immunity, bind and present intracellular Ags to CD8+ T cells. The extreme polymorphism of HLA genes and associated peptide binding specificities leads to challenges in various endeavors, including neoantigen vaccine development, disease association studies, and HLA typing. Supertype classification, defined by clustering functionally similar HLA alleles, has proven helpful in reducing the complexity of distinguishing alleles. However, determining supertypes via experiments is impractical, and current in silico classification methods exhibit limitations in stability and functional relevance. In this study, by incorporating three-dimensional structures we present a method for classifying HLA class I molecules with improved breadth, accuracy, stability, and flexibility. Critical for these advances is our finding that structural similarity highly correlates with peptide binding specificity. The new classification should be broadly useful in peptide-based vaccine development and HLA–disease association studies.
Increased levels of circulating platelet microparticles as a risk of hypercoagulable state in β-thalassemia intermedia patients
Authors: Abdel Aziz Hanan M. , El-Beih Esam A.S. , Sayed Douaa M. , Afifi Ola A. , Thabet Ahmad F. , Elgammal Sahar , Mansor Shima G. , Moeen Sawsan M. 
Published: January 2023

Introduction
Thromboembolism is a frequent complication in thalassemia. Platelet microparticles (PMPs) may have a role in the hypercoagulability in thalassemia.

Objective
To determine the levels of PMPs in β-thalassemia intermedia (β-TI) patients and whether increased levels of PMPs in these patients are correlated with coagulation parameters or not.

Patients and methods
Sixty-three β-TI patients, classified into 46 nonsplenectomized (NS) patients, 17 splenectomized (S) patients, and 20 age-matched and sex-matched volunteers as controls. For all, full medical history, through clinical examination, and laboratory investigations: complete blood count, prothrombin time, prothrombin concentration, activated partial thromboplastin time, FVIII, FXI, fibrinogen, D-dimer, and PMPs were detected by using flow-cytometry approach.

Results
PMPs were significantly higher in S and NS β-TI patients than controls (P<0.001, P=0.002), respectively. FVIII and D-dimer were significantly higher in S patients than controls (P=0.004, 0.048), respectively. Fibrinogen level was significantly lower in both NS and S β-TI patients than in controls (P<0.001). A significant positive correlation between PMPs and platelet count in S patients (r=0.549, P=0.023).

Conclusion
Thrombotic risk in β-TI patients is related to increased circulating PMPs and platelet count. Splenectomy was considered a risk factor of thrombosis in our study.
Allergens in Corticosteroid Vehicles in Saudi Arabia
Authors: Alharbi Mana , Almutairi Seba , Alfalah Maisa 
Published: January 2023

Background:
Both the active steroid compounds and vehicle ingredients of the topical corticosteroid products can cause allergic contact dermatitis.

Purpose:
The objective of the current study was to assess the presence of allergens in topical corticosteroid vehicles used in Saudi Arabia.

Methods:
Package inserts of topical corticosteroid products available through February 2022 were reviewed independently by two dermatologists. Topical corticosteroids were excluded if they were not approved by the Saudi Food and Drug Authority.

Results:
Out of 79 products examined, 49 (62%) were included in the study. Out of the 49 products, 29 (59%) had one or more allergens (a total of 38 allergens). Three topical corticosteroids were responsible for more than 80% of all allergens. These included mometasone furoate (n = 12), clobetasol propionate (n = 7), and betamethasone valerate (n = 5). The most frequent allergens were propylene glycol (66%), parabens (16%), sorbitan (13%), and lanolin (5%). Formaldehyde(s), methylchloro-isothiazolinone, and methyl-isothiazolinone were not detected in any product. Approximately 48% of the products with allergens were creams, 41% were ointments, and 10% were lotions. With two exceptions, there were no statistically significant differences in the overall presence of allergens by the type, formulation, and concentration of topical corticosteroid products.

Conclusion:
Almost 60% of topical corticosteroid products widely used in dermatologic clinics in Saudi Arabia had one or more vehicle allergens. Since the best treatment for contact allergy is avoidance, dermatologists should be aware of vehicle allergens in topical corticosteroids and consider the use of allergen-free products.
Clinical, ultrasonic, and histopathologic evaluation of autologous fat transplantation plus platelet-rich plasma with versus without fractional carbon dioxide laser in the treatment of aging hands
Authors: Elgayar Maha A. , Hegazy Safwat A. , Saied Eman M. , Hassib Mona T. , Elseessy Noura A.M.M. 
Published: January 2023

Background
Aging hands show soft tissue atrophy with prominent bones, tendons, and visible veins as well as pigmented changes and skin rhytids. Autologous fat grafting (AFG) combined with platelet-rich plasma (PRP) sessions can be used in hand rejuvenation for improvement of cutaneous and subcutaneous defects with long lasting results.

Objective
To evaluate the efficacy, tolerability, and possible side effects of AFG plus PRP with versus without fractional carbon dioxide (CO2) laser in hand rejuvenation.

Patients and methods
This comparative randomized study included 60 apparently healthy participants in need for hand rejuvenation who were divided into two groups: group I, two hands of 30 participants were treated by AFG with PRP and fractional CO2 laser. Group II, two hands of 30 participants were treated by AFG with PRP. The evaluation was done by clinical evaluation, ultrasound scanning, histopathology, and patient satisfaction. Participants were followed up for 6 months.

Results
Significant improvement was detected on both groups after treatment with no significant difference between both sides by clinical evaluation, ultrasound scanning, histopathologic evaluation, and patient satisfaction that persisted for 6 months. However, addition of fractional CO2 laser produced significant improvement in skin pigmentation and improvement with nonsignificant difference in wrinkling.

Conclusion
The enriched AFG with PRP was very effective and safe in the treatment of hand aging especially in volume restoration and disappearance of visible underlying structures. Moreover, fractional CO2 laser produced more improvement in skin pigmentation.
Polynomially growing harmonic functions on connected groups
Authors: Perl Idan , Yadin Ariel 
Published: January 2023

We study the connection between the dimension of certain spaces of harmonic functions on a group and its geometric and algebraic properties.
Our main result shows that (for sufficiently “nice” random walk measures) a connected, compactly generated, locally compact group has polynomial volume growth if and only if the space of linear growth harmonic functions has finite dimension.
This characterization is interesting in light of the fact that Gromov’s theorem regarding finitely generated groups of polynomial growth does not have an analog in the connected case. That is, there are examples of connected groups of polynomial growth that are not nilpotent by compact. Also, the analogous result for the discrete case has only been established for solvable groups and is still open for general finitely generated groups.
Risk of COVID-19 infection and severity of clinical outcomes and its association with ABO blood groups
Authors: Shah Tazeen , Mahar Benazir , Warsi Jamshed , Shaikh Farheen , Hassan Ameer , Rind Ali Hamza 
Published: January 2023

Objective: To determine association of ABO blood groups with severity of COVID-19 symptoms among covid recovered patients of different blood type. Methodology: An observational/experimental study was conducted at department of physiology, Sindh university Jamshoro from April 2021 to December 2021.The sample size (n) was 732, data consist of male and female covid recovered participants of age group 18-30yrs. Self -structured questionnaire was used to evaluate intensity of symptoms of COVID 19 and for other characteristics such as gender and age. Blood was drawn for ABO blood typing. Statistical analysis was performed on SPSS- 21.Results: Seven hundred thirty two was the total study population of COVID-19 recovered patients, out of which male population was 489 (66.9%) and female population was 243 (33.1%).The results reports that there is statistically significant association present between the A +ve blood type and susceptibility of COVID-19 infection, whereas AB +ve and A +ve shown higher percentage of severe infection. Blood group B +ve with (48%) with less severe symptoms. O +ve people shown mild symptoms that is 60% of entire O+ve population and 30% are presented with severe symptoms.Conclusion: This study suggests that A +ve blood group is susceptible blood type with high chances to get infection. People having A +ve and AB +ve blood types are more susceptible towards severe COVID 19 infection in comparison to other blood types, O +ve blood shown rather protective effect.
AIR PERASAN DAUN KESUM (Polygonum minus Huds) MENGHAMBAT PERTUMBUHAN Candida albicans
Authors: Syari Jajar Pramata , Sungkawa Hendra Budi , Sutriswanto Sutriswanto , Ratnawaty Gervacia Jenny 
Published: January 2023

Penyakit yang disebabkan oleh jamur sering ditemui salah satunya yaitu infeksi pada vulva atau vagina (kandidiasis vulvovaginalis) dikarenakan pertumbuhan yang tidak terkendali dari jamur Candida sp., terutama Candida albicans. . Kandidiasis vulvovaginalis merupakan penyebab keputihan yang paling sering, prevalensinya sebesar 40%, dengan karakteristik cairan yang keluar biasanya kental, putih seperti susu, bau, dan disertai rasa gatal yang hebat pada kemaluan. Berdasarkan kajian fitofarmaka, diduga tanaman kesum memiliki aktivitas antiviral, antibakteri, antijamur, antioksidan, antikanker dan antiulcer. Tanaman daun kesum dapat digunakan sebagai obat yang diakibatkan oleh jamur. Daun kesum (Polygonum minus Huds.) mengandung senyawa-senyawa metabolit sekunder yang dapat digunakan sebagai antifungi. Metabolit sekunder tersebut berupa flavonoid, aldehid, terpenoid, gerniol dan senyawa fenolik. Tujuan penelitian ini adalah mengetahui jumlah koloni jamur Candida albicans pada plate yang diberikan perasan daun kesum (Polygonum minus Huds), aktivitas air perasan daun kesum (Polygonum minus Huds) dan menganalisis pengaruh air perasan daun kesum (Polygonum minus Huds) terhadap daya hambat pertumbuhan jamur Candida albicans metode dilusi. Metodologi penelitian ini merupakan Quasi Experimental Design. Berdasarkan Uji Anova Aktivitas Air Perasan Daun Kesum (Polygonum minus Huds) Terhadap Pertumbuhan Jamur Candida albicans Metode Dilusi diperoleh tingkat signifikansi p = 0,000 < α (0,05) dan dinyatakan bahwa H1 diterima, artinya terdapat pengaruh yang nyata (signifikan) antara variabel bebas (air perasan daun kesum) terhadap variabel terikat (pertumbuhan jamur Candida albicans).
Alternative Procedures and Quality of Financial Report Audit Results in the Era of the Covid 19 Pandemic
Authors: Jassin Rivcy , Tinangon Jantje. J , Budiarso Novi Swandari 
Published: January 2023

This study aims to determine the implementation, constraints, efforts to overcome obstacles, and the result audit quality when using the alternative procedures for auditing local government financial report (LKPD) which is conducted by The Representative of Audit Board Indonesia in North Sulawesi Province (BPK of North Sulawesi) in the Covid 19 Pandemic Era.This study uses a qualitative method with a case study approach. The data was collected through interviews and documentation studies. The results showed that The Representative of Audit Board Indonesia in North Sulawesi Province had implemented alternative procedures for auditing local government financial report by preparing adequate regulations and policies. Improving the competence of the auditor through training, workshops, socialization, dissemination, knowledge transfer forum, compiling Frequently Asked Questions (FAQ), and making messenger group. In addition, preparing an audit program that accommodates alternative procedures in accordance with existing regulations, developing audit strategies and alternative procedures through the utilization of the Internal Government Supervisory Apparatus (APIP), utilizing information technology, and tiered reviews. Problem that faced in implementing alternative procedures are the lack of local government commitment in preparing a stable internet network, supporting devices, personnel in related office, the number of competent APIP teams as needed. Lack experience auditor does not have the same knowledge about the details of steps and supporting documents. These issues can be overcome through increasing local government commitment, the number competence APIP team as needed, and the competence of new auditor of Audit Board Indonesia.The quality of audit results in the era of the Covid 19 pandemic has fulfilled the requirement with indicators of quality control and quality assurance achievements, the achievement of the auditee satisfaction index for LKPD examinations, the achievement of timely submission of LKPD audit report (LHP LKPD), and the achievement of the percentage of lawsuits against LHP won by the Audit Board of Indonesia
تأثير اضافة المعزز الحيوي (Probiotic) لمياه الشرب على اداء فروج اللحم تحت ظروف موسم الصيف الحار
Authors: Salam Omar Abdul Majead , Hassan Osan Mohammed Saleh 
Published: January 2023

اجريت التجربة في حظيرة الدواجن في كلية ناصر للعلوم الزراعية جامعة عدن خلال الفترة من 2021/7/8م لغاية 2021/8/11م وذلك لمعرفة تأثير اضافة المعزز الحيوي (Probiotic) (0، 50، 100ملجم/لتر ماء) تحت ظروف فصل الصيف الحار استخدم في التجربة 108 فروج من نوع R0SS، وزعت عشوائيا الى ثلاث معاملات بواقع 36 فروج لكل معاملة وثلاثة مكررات لكل معاملة وبواقع 12 فروج في كل مكرر. اشارت النتائج الى عدم وجود فروق معنوية بين المعاملات المختلفة في معظم الصفات المدروسة (معدل استهلاك العلف، معامل التحويل الغذائي، نسبة النفوق، انتاجية المتر المربع من الوزن الحي) ولكن كان هناك تحسن أفضل في معاملات اضافة المعزز الحيوي (Probiotic). في حين لوحظ ان اضافة المعزز الحيوي (Probiotic) كانت معنويا عند مستوى احتمال (P<0.05) في صفة وزن الجسم ومعدل الزيادة الوزنية.