bluuebunny/crossref_metadata_2025_split huggingface dataset:
Candidate loci shared among periodontal disease, diabetes and bone density
Authors: Yu Yau-Hua , Steffensen Bjorn , Ridker Paul M. , Buring Julie E. , Chasman Daniel I. 
Published: January 2023

IntroductionWhile periodontal disease (PD) has been associated with type 2 diabetes (T2D) and osteoporosis, the underlying genetic mechanisms for these associations remain largely unknown. The aim of this study is to apply cross-trait genetic analyses to investigate the potentially shared biology among PD, T2D, and bone mineral density (BMD) by assessing pairwise genetic correlations and searching for shared polymorphisms.MethodsWe applied cross-trait genetic analyses leveraging genome-wide association study (GWAS) summary statistics for: Periodontitis/loose teeth from the UKBB/GLIDE consortium (PerioLT, N=506594), T2D from the DIAGRAM consortium (Neff=228825), and BMD from the GEFOS consortium (N=426824). Among all three, pair-wise genetic correlations were estimated with linkage disequilibrium (LD) score regression. Multi-trait meta-analysis of GWAS (MTAG) and colocalization analyses were performed to discover shared genome-wide significant variants (pMTAG &lt;5x10-8). For replication, we conducted independent genetic analyses in the Women’s Genome Health Study (WGHS), a prospective cohort study of middle-aged women of whom 14711 provided self-reported periodontal disease diagnosis, oral health measures, and periodontal risk factor data including incident T2D.ResultsSignificant genetic correlations were identified between PerioLT/T2D (Rg=0.23; SE=0.04; p=7.4e-09) and T2D/BMD (Rg=0.09; SE=0.02; p=9.8e-06). Twenty-one independent pleiotropic variants were identified via MTAG (pMTAG&lt;5x10-8 across all traits). Of these variants, genetic signals for PerioLT and T2D colocalized at one candidate variant (rs17522122; ProbH4 = 0.58), a 3’UTR variant of AKAP6. Colocalization between T2D/BMD and the original PerioLT GWAS p-values suggested 14 additional loci. In the independent WGHS sample, which includes responses to a validated oral health questionnaire for PD surveillance, the primary shared candidate (rs17522122) was associated with less frequent dental flossing [OR(95%CI)= 0.92 (0.87-0.98), p=0.007], a response that is correlated with worse PD status. Moreover, 4 additional candidate variants were indirectly supported by associations with less frequent dental flossing [rs75933965, 1.17(1.04-1.31), p=0.008], less frequent dental visits [rs77464186, 0.82(0.75-0.91), p=0.0002], less frequent dental prophylaxis [rs67111375, 0.91(0.83-0.99), p=0.03; rs77464186, 0.80(0.72-0.89), p=3.8e-05], or having bone loss around teeth [rs8047395, 1.09(1.03-1.15), p=0.005].DiscussionThis integrative approach identified one colocalized locus and 14 additional candidate loci that are shared between T2D and PD/oral health by comparing effects across PD, T2D and BMD. Future research is needed to independently validate our findings.
The TNAPP web-based algorithm improves thyroid nodule management in clinical practice: A retrospective validation study
Authors: Triggiani Vincenzo , Lisco Giuseppe , Renzulli Giuseppina , Frasoldati Andrea , Guglielmi Rinaldo , Garber Jeffrey , Papini Enrico 
Published: January 2023

BackgroundThe detection of thyroid nodules has been increasing over time, resulting in an extensive use of fine-needle aspiration (FNA) and cytology. Tailored methods are required to improve the management of thyroid nodules, including algorithms and web-based tools.Study aimsTo assess the performance of the Thyroid Nodule App (TNAPP), a web-based, readily modifiable, interactive algorithmic tool, in improving the management of thyroid nodules.MethodsOne hundred twelve consecutive patients with 188 thyroid nodules who underwent FNA from January to December 2016 and thyroid surgery were retrospectively evaluated. Neck ultrasound images were collected from a thyroid nodule registry and re-examined to extract data to run TNAPP. Each nodule was evaluated for ultrasonographic risk and suitability for FNA. The sensitivity, specificity, positive and negative predictive values, and overall accuracy of TNAPP were calculated and compared to the diagnostic performance of the other two algorithms by the American Association of Clinical Endocrinology/American College of Endocrinology/Associazione Medici Endocrinologi (AACE/ACE/AME), which it was derived from the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS).ResultsTNAPP performed better in terms of sensitivity (&gt;80%) and negative predictive value (68%) with an overall accuracy of 50.5%, which was similar to that found with the AACE/ACE/AME algorithm. TNAPP displayed a slightly better performance than AACE/ACE/AME and ACR TI-RADS algorithms in selectively discriminating unnecessary FNA for nodules with benign cytology (TIR 2 - Bethesda class II: TNAPP 32% vs. AACE/ACE/AME 31% vs. ACR TI-RADS 29%). The TNAPP reduced the number of missed diagnoses of thyroid nodules with suspicious and highly suspicious cytology (TIR 4 + TIR 5 - Bethesda classes V + VI: TNAPP 18% vs. AACE/ACE/AME 26% vs. ACR TI-RADS 20.5%). A total of 14 nodules that would not have been aspirated were malignant, 13 of which were microcarcinomas (92.8%).DiscussionThe TNAPP algorithm is a reliable, easy-to-learn tool that can be readily employed to improve the selection of thyroid nodules requiring cytological characterization. The rate of malignant nodules missed because of inaccurate characterization at baseline by TNAPP was lower compared to the other two algorithms and, in almost all the cases, the tumors were microcarcinomas. TNAPP’s use of size &gt;20 mm as an independent determinant for considering or recommending FNA reduced its specificity.ConclusionTNAPP performs well compared to AACE/ACE/AME and ACR-TIRADS algorithms. Additional retrospective and, ultimately, prospective studies are needed to confirm and guide the development of future iterations that incorporate different risk stratification systems and targets for diagnosing malignancy while reducing unnecessary FNA procedures.
Association between body fat and sarcopenia in older adults with type 2 diabetes mellitus: A cross-sectional study
Authors: Sun Lina , Fu Junling , Mu Zhijing , Duan Xiaoye , Chan Piu , Xiu Shuangling 
Published: January 2023

ObjectivesTo investigate the association between body fat (BF%) and sarcopenia in older adults with type 2 diabetes mellitus (T2DM) and potential link with increased levels of inflammatory indicators and insulin resistance.MethodsA total of 543 older adults with T2DM were included in this cross-sectional study. Appendicular skeletal muscle (ASM), handgrip strength and gait speed were measured to diagnose sarcopenia according to the updated Asian Working Group for Sarcopenia (AWGS) 2019 criteria. Body composition data were tested using dual-energy X-ray absorptiometry (DEXA). Levels of serum high-sensitive C-reactive protein (hs-CRP), interleukin-6, fasting blood insulin (FINS), hemoglobin A1c (HbA1c), 25-hydroxyvitamin D3 [25(OH) D3] were also determined.ResultsThe prevalence of sarcopenia in all participants was 8.84%, of which 11.90% were male and 5.84% females. The Pearson’s correlation analysis revealed that BF% was negatively correlated with gait speed in men and women (R =-0.195, P=0.001; R = -0.136, P =0.025, respectively). After adjusting for all potential confounders, sarcopenia was positive associated with BF% (male, OR: 1.38, 95% CI: 1.15–1.65, P&lt; 0.001; female, OR: 1.30, 95% CI: 1.07–1.56, P=0.007), and negatively associated with body mass index (BMI) (male, OR: 0.57, 95% CI: 0.44–0.73, P&lt;0.001; female, OR: 0.48, 95% CI: 0.33–0.70, P&lt;0.001). No significant differences were found in hs-CRP, interleukin-6, and insulin resistance between older T2DM adults with and without sarcopenia.ConclusionHigher BF% was linked to an increased risk of sarcopenia in older adults with T2DM, suggesting the importance of assessing BF% rather than BMI alone to manage sarcopenia.
Advances in phytoplankton population ecology in the Pearl river estuary
Authors: Chen Wenlong , Guo Fang , Huang Weijie , Wang Jianguo , Zhang Min , Wu Qian 
Published: January 2023

Phytoplankton is an important primary producer of the estuarine ecosystem, which is essential for the biogeochemical cycle of water elements and nutrient transfer. The Pearl River estuary (PRE) is a dynamically complex estuary, and the environment of PRE is significantly impacted by anthropogenic activities, variation of phytoplankton community structure in the PRE are complex. This review aims to compare phytoplankton species, species diversity, and abundance variation characteristics from the 1980s and 2020s, evaluate the overall trend of phytoplankton in the PRE, and discuss the main environmental factors affecting phytoplankton growth in the PRE. The data from the past 40 years in PRE showed that the number of phytoplankton species significantly decreased (p &lt; 0.05). There was no significant difference in the abundance of phytoplankton at the 10-year scale, however, the fluctuation range of the abundance has increased. Under the conditions of a decreasing species number and no significant difference in abundance, the species diversity of phytoplankton showed a downward trend. In addition, the dominant phytoplankton species in the nearshore waters were relatively homogenous, and the abundance of phytoplankton in the nearshore waters was higher than that in the open waters, which suggested that human activities have a great influence. This review can form the basis for facilitating health management in the PRE ecosystem. Further, relevant guidelines can be developed and implemented for promoting the ecological health of the Guangdong-Hong Kong-Macao Greater Bay Area and ensuring its sustainable development.
Arachidonate lipoxygenases 5 is a novel prognostic biomarker and correlates with high tumor immune infiltration in low-grade glioma
Authors: Pan Rui-han , Zhang Xin , Chen Zu-peng , Liu Ya-jun 
Published: January 2023

Objective: To investigate the prognostic value of arachidonate lipoxygenases 5 (ALOX5) expression and methylation, and explore the immune functions of arachidonate lipoxygenases 5 expression in low-grade glioma (LGG).Materials and Methods: Using efficient bioinformatics approaches, the differential expression of arachidonate lipoxygenases 5 and the association of its expression with clinicopathological characteristics were evaluated. Then, we analyzed the prognostic significance of arachidonate lipoxygenases 5 expression and its methylation level followed by immune cell infiltration analysis. The functional enrichment analysis was conducted to determine the possible regulatory pathways of arachidonate lipoxygenases 5 in low-grade glioma. Finally, the drug sensitivity analysis was performed to explore the correlation between arachidonate lipoxygenases 5 expression and chemotherapeutic drugs.Results: arachidonate lipoxygenases 5 mRNA expression was increased in low-grade glioma and its expression had a notable relation with age and subtype (p &lt; 0.05). The elevated mRNA level of arachidonate lipoxygenases 5 could independently predict the disease-specific survival (DSS), overall survival (OS), and progression-free interval (PFI) (p &lt; 0.05). Besides, arachidonate lipoxygenases 5 expression was negatively correlated with its methylation level and the arachidonate lipoxygenases 5 hypomethylation led to a worse prognosis (p &lt; 0.05). The arachidonate lipoxygenases 5 expression also showed a positive connection with immune cells, while low-grade glioma patients with higher immune cell infiltration had poor survival probability (p &lt; 0.05). Further, arachidonate lipoxygenases 5 might be involved in immune- and inflammation-related pathways. Importantly, arachidonate lipoxygenases 5 expression was negatively related to drug sensitivity.Conclusion: arachidonate lipoxygenases 5 might be a promising biomarker, and it probably occupies a vital role in immune cell infiltration in low-grade glioma.
Breadth of Antibodies to Plasmodium falciparum Variant Surface Antigens Is Associated With Immunity in a Controlled Human Malaria Infection Study
Authors: Kimingi Hannah W. , Kinyua Ann W. , Achieng Nicole A. , Wambui Kennedy M. , Mwangi Shaban , Nguti Roselyne , Kivisi Cheryl A. , Jensen Anja T. R. , Bejon Philip , Kapulu Melisa C. , Abdi Abdirahman I. , Kinyanjui Samson M. ,   CHMI-SIKA Study Team
Published: January 2023

BackgroundPlasmodium falciparum variant surface antigens (VSAs) contribute to malaria pathogenesis by mediating cytoadhesion of infected red blood cells to the microvasculature endothelium. In this study, we investigated the association between anti-VSA antibodies and clinical outcome in a controlled human malaria infection (CHMI) study.MethodWe used flow cytometry and ELISA to measure levels of IgG antibodies to VSAs of five heterologous and one homologous P. falciparum parasite isolates, and to two PfEMP1 DBLβ domains in blood samples collected a day before the challenge and 14 days after infection. We also measured the ability of an individual’s plasma to inhibit the interaction between PfEMP1 and ICAM1 using competition ELISA. We then assessed the association between the antibody levels, function, and CHMI defined clinical outcome during a 21-day follow-up period post infection using Cox proportional hazards regression.ResultsAntibody levels to the individual isolate VSAs, or to two ICAM1-binding DBLβ domains of PfEMP1, were not associated with a significantly reduced risk of developing parasitemia or of meeting treatment criteria after the challenge after adjusting for exposure. However, anti-VSA antibody breadth (i.e., cumulative response to all the isolates) was a significant predictor of reduced risk of requiring treatment [HR 0.23 (0.10-0.50) p= 0.0002].ConclusionThe breadth of IgG antibodies to VSAs, but not to individual isolate VSAs, is associated with protection in CHMI.
Clinical and immunological features of an APLAID patient caused by a novel mutation in PLCG2
Authors: Peng Qi , Luo Dong , Yang Yi , Zhu Yinghua , Luo Qingming , Chen Huan , Chen Dapeng , Zhou Zhongjun , Lu Xiaomei 
Published: January 2023

BackgroundThe APLAID syndrome is a rare primary immunodeficiency caused by gain-of-function mutations in the PLCG2 gene. We present a 7-year-old APLAID patient who has recurrent blistering skin lesions, skin infections in the perineum, a rectal perineal fistula, and inflammatory bowel disease.MethodsTo determine the genetic cause of our patient, WES and bioinformatics analysis were performed. Flow cytometry was used for phenotyping immune cell populations in peripheral blood. Cytokines released into plasma were analyzed using protein chip technology. The PBMCs of patient and a healthy child were subjected to single-cell RNA-sequencing analysis.ResultsThe patient carried a novel de novo missense mutation c.2534T&gt;C in exon 24 of the PLCG2 gene that causes a leucine to serine amino acid substitution (p.Leu845Ser). Bioinformatics analysis revealed that this mutation had a negative impact on the structure of the PLCγ2 protein, which is highly conserved in many other species. Immunophenotyping by flow cytometry revealed that in addition to the typical decrease in circulating memory B cells, the levels of myeloid dendritic cells (mDCs) in the children’s peripheral blood were significantly lower, as were the CD4+ effector T cells induced by their activation. Single-cell sequencing revealed that the proportion of different types of cells in the peripheral blood of the APLAID patient changed.ConclusionsWe present the first case of APLAID with severely reduced myeloid dendritic cells carrying a novel PLCG2 mutation, and conducted a comprehensive analysis of immunological features in the ALPAID patient, which has not been mentioned in previous reports. This study expands the spectrum of APLAID-associated immunophenotype and genotype. The detailed immune analyses in this patient may provide a basis for the development of targeted therapies for this severe autoinflammatory disease.
Diagnostic and prognostic value of serum S100B in sepsis-associated encephalopathy: A systematic review and meta-analysis
Authors: Hu Jiyun , Xie Shucai , Li Wenchao , Zhang Lina 
Published: January 2023

BackgroundIn sepsis, brain dysfunction is known as Sepsis-associated encephalopathy (SAE), which often results in severe cognitive and neurological sequelae and increases the risk of death. Our systematic review and meta-analysis aimed to explore the diagnostic and prognostic value of serum S100 calcium-binding protein B (S100B) in SAE patients.MethodsWe conducted a systematic search of the databases PubMed, Web of Science, Embase, Cochrane databases, CNKI, VIP, and WFSD from their inception dates until August 20, 2022. A Meta-analysis of the included studies was also performed using Review Manager version 5.4 and Stata16.0.ResultsThis meta-analysis included 28 studies with 1401 serum samples from SAE patients and 1591 serum samples from no-encephalopathy septic (NE) patients. The Meta-Analysis showed that individuals with SAE had higher serum S100B level than NE controls (MD, 0.49 [95% CI (0.37)-(0.60), Z =8.29, P &lt; 0.00001]), and the baseline level of serum S100B in septic patients with burn was significantly higher than average (1.96 [95% CI (0.92)-(2.99), Z =3.71, P &lt; 0.0002]) In addition, septic patients with favorable outcomes had lower serum S100B levels than those with unfavorable outcomes (MD, -0.35 [95% CI (-0.50)-(-0.20), Z =4.60, P &lt; 0.00001]).ConclusionOur Meta-Analysis indicates that higher serum S100B level in septic patients are moderately associated with SAE and unfavorable outcomes (The outcomes here mainly refer to the mortality). The serum S100B level may be a useful diagnostic and prognostic biomarker of SAE.
Neutralizing antibodies to Omicron after the fourth SARS-CoV-2 mRNA vaccine dose in immunocompromised patients highlight the need of additional boosters
Authors: Rescigno Maria , Agrati Chiara , Salvarani Carlo , Giannarelli Diana , Costantini Massimo , Mantovani Alberto , Massafra Raffaella , Zinzani Pier Luigi , Morrone Aldo , Notari Stefania , Matusali Giulia , Pinter Giuseppe Lauria , Uccelli Antonio , Ciliberto Gennaro , Baldanti Fausto , Locatelli Franco , Silvestris Nicola , Sinno Valentina , Turola Elena , Lupo-Stanghellini Maria Teresa , Apolone Giovanni ,   the VAX4FRAIL study Group
Published: January 2023

IntroductionImmunocompromised patients have been shown to have an impaired immune response to COVID-19 vaccines.MethodsHere we compared the B-cell, T-cell and neutralizing antibody response to WT and Omicron BA.2 SARS-CoV-2 virus after the fourth dose of mRNA COVID-19 vaccines in patients with hematological malignancies (HM, n=71), solid tumors (ST, n=39) and immune-rheumatological (IR, n=25) diseases. The humoral and T-cell responses to SARS-CoV-2 vaccination were analyzed by quantifying the anti-RBD antibodies, their neutralization activity and the IFN-γ released after spike specific stimulation.ResultsWe show that the T-cell response is similarly boosted by the fourth dose across the different subgroups, while the antibody response is improved only in patients not receiving B-cell targeted therapies, independent on the pathology. However, 9% of patients with anti-RBD antibodies did not have neutralizing antibodies to either virus variants, while an additional 5.7% did not have neutralizing antibodies to Omicron BA.2, making these patients particularly vulnerable to SARS-CoV-2 infection. The increment of neutralizing antibodies was very similar towards Omicron BA.2 and WT virus after the third or fourth dose of vaccine, suggesting that there is no preferential skewing towards either virus variant with the booster dose. The only limited step is the amount of antibodies that are elicited after vaccination, thus increasing the probability of developing neutralizing antibodies to both variants of virus.DiscussionThese data support the recommendation of additional booster doses in frail patients to enhance the development of a B-cell response directed against Omicron and/or to enhance the T-cell response in patients treated with anti-CD20.
Efficacy of ixekizumab in patients with moderate-to-severe plaque psoriasis and prediabetes or type 2 diabetes
Authors: Egeberg Alexander , Merola Joseph F. , Schäkel Knut , Puig Luis , Mahar Patrick D. , Wang Isabella Yali , Pavo Imre , Schuster Christopher , Griffiths Christopher E. M. 
Published: January 2023

ObjectivePatients with psoriasis have an increased prevalence of type 2 diabetes when compared to the general population. Research suggests that type 2 diabetes (T2D) as well as obesity may have an impact on patients' response to treatment. This post-hoc analysis reports the efficacy of ixekizumab in treating moderate-to-severe psoriasis in patients with prediabetes or T2D.Method and materialsUNCOVER-1, UNCOVER-2, and UNCOVER-3 were three Phase 3, multicenter, randomized, double-blind, placebo-controlled trials that evaluated the efficacy and safety of ixekizumab in adult patients with moderate-to-severe psoriasis. Patients were aged ≥18 years with chronic moderate-to-severe psoriasis (defined as ≥10% body surface area affected, static Physician Global Assessment ≥3, and Psoriasis Area and Severity Index [PASI] ≥12 at screening and baseline) who were candidates for phototherapy or systemic therapy. UNCOVER-1, UNCOVER-2, and UNCOVER-3 participants received ixekizumab as per label (that is, an initial dose of two subcutaneous injections [160 mg in total] at Week 0, followed by 80 mg every 2 weeks through Week 12 and 80 mg every 4 weeks thereafter through Week 60).ResultsThe proportions of patients with prediabetes, T2D and normoglycemia that achieved PASI75, PASI90, and PASI100 at Week 60 were similar. Results suggest that patients with T2D were slower to achieve PASI100 than patients with prediabetes or those with normoglycemia. Ixekizumab had no effect on any metabolic markers in patients receiving the treatment.ConclusionsDespite the higher rate of obesity and extreme obesity in patients with prediabetes and T2D, ixekizumab was an efficacious treatment in treating patients with psoriasis.