bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are fungicides a driver of European foulbrood disease in honey bee colonies pollinating blueberries?
Authors: Thebeau Jenna M. , Cloet Allyssa , Liebe Dana , Masood Fatima , Kozii Ivanna V. , Klein Colby D. , Zabrodski Michael W. , Biganski Sarah , Moshynskyy Igor , Sobchishin Larhonda , Wilson Geoff , Guarna Maria Marta , Gerbrandt Eric M. , Ruzzini Antonio , Simko Elemir , Wood Sarah C. 
Published: January 2023

IntroductionBlueberry producers in Canada depend heavily on pollination services provided by honey bees (Apis mellifera L.). Anecdotal reports indicate an increased incidence of European foulbrood (EFB), a bacterial disease caused by Melissococcus plutonius, is compromising pollination services and colony health. Fungicidal products are commonly used in blueberry production to prevent fungal diseases such as anthracnose and botrytis fruit rot. Pesticide exposure has been implicated in honey bee immunosuppression; however, the effects of commercial fungicidal products, commonly used during blueberry pollination, on honey bee larval susceptibility to EFB have not been investigated.MethodsUsing an in vitro infection model of EFB, we infected first instar honey bee larvae with M. plutonius 2019 BC1, a strain isolated from an EFB outbreak in British Columbia, Canada, and chronically exposed larvae to environmentally relevant concentrations of fungicide products over 6 days. Survival was monitored until pupation or eclosion.ResultsWe found that larvae chronically exposed to one, two, or three fungicidal products [Supra® Captan 80WDG (Captan), low concentration of Kenja™ 400SC (Kenja), Luna® Tranquility (Luna), and/or Switch® 62.5 WG (Switch)], did not significantly reduce survival from EFB relative to infected controls. When larvae were exposed to four fungicide products concurrently, we observed a significant 24.2% decrease in survival from M. plutonius infection (p = 0.0038). Similarly, higher concentrations of Kenja significantly reduced larval survival by 24.7–33.0% from EFB (p &lt; 0.0001).DiscussionThese in vitro results suggest that fungicides may contribute to larval susceptibility and response to M. plutonius infections. Further testing of other pesticide combinations is warranted as well as continued surveillance of pesticide residues in blueberry-pollinating colonies.
Assessment of bidirectional relationships between circulating cytokines and periodontitis: Insights from a mendelian randomization analysis
Authors: Huang Shi-Jia , Li Rong , Xu Shuo , Liu Yuan , Li Sheng-Hui , Duan Sheng-Zhong 
Published: January 2023

Background: The purpose of this Mendelian randomization (MR) study was to assess the causal relationship between circulating cytokines and periodontitis.Materials and methods: Based on the aggregated statistics of the largest publicly available genome-wide association study (GWAS), we applied a bidirectional two-sample MR. MR analyses were conducted using Inverse variance weighted (IVW), Robust Adjusted Profile Score (RAPS), Maximum likelihood (ML), Weighted median and MR-Egger, and results obtained from IVW served as the primary outcome. Cochran Q test was used to test the heterogeneity. MR-Egger intercept test and MR polymorphism residual and outlier test (MR-PRESSO) were used for polymorphism analysis. Leave-one-out sensitivity and funnel plots were used for sensitivity analysis.Results: The IVW method indicated that interleukin 9 (IL9) had a positive causal relationship with periodontitis [odds ratio (OR) = 1.199, 95% confidence interval (CI) = 1.049–1.372, p = 0.008], and interleukin 17 (IL17) had a negative causal relationship with periodontitis (OR = 0.847, 95% CI = 0.735–0.976, p = 0.022). In bidirectional MR, periodontitis was not causally related to any of the cytokines in our study.Conclusion: Our findings provided evidence in support of potential causal associations between circulating IL9/IL17 and periodontitis.
CFH and CFHR structural variants in atypical Hemolytic Uremic Syndrome: Prevalence, genomic characterization and impact on outcome
Authors: Piras Rossella , Valoti Elisabetta , Alberti Marta , Bresin Elena , Mele Caterina , Breno Matteo , Liguori Lucia , Donadelli Roberta , Rigoldi Miriam , Benigni Ariela , Remuzzi Giuseppe , Noris Marina 
Published: January 2023

IntroductionAtypical hemolytic uremic syndrome (aHUS) is a rare disease that manifests with microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure, and is associated with dysregulation of the alternative complement pathway. The chromosomal region including CFH and CFHR1-5 is rich in repeated sequences, favoring genomic rearrangements that have been reported in several patients with aHUS. However, there are limited data on the prevalence of uncommon CFH-CFHR genomic rearrangements in aHUS and their impact on disease onset and outcomes.MethodsIn this study, we report the results of CFH-CFHR Copy Number Variation (CNV) analysis and the characterization of resulting structural variants (SVs) in a large cohort of patients, including 258 patients with primary aHUS and 92 with secondary forms.ResultsWe found uncommon SVs in 8% of patients with primary aHUS: 70% carried rearrangements involving CFH alone or CFH and CFHR (group A; n=14), while 30% exhibited rearrangements including only CFHRs (group B; n=6). In group A, 6 patients presented CFH::CFHR1 hybrid genes, 7 patients carried duplications in the CFH-CFHR region that resulted either in the substitution of the last CFHR1 exon(s) with those of CFH (CFHR1::CFH reverse hybrid gene) or in an internal CFH duplication. In group A, the large majority of aHUS acute episodes not treated with eculizumab (12/13) resulted in chronic ESRD; in contrast, anti-complement therapy induced remission in 4/4 acute episodes. aHUS relapse occurred in 6/7 grafts without eculizumab prophylaxis and in 0/3 grafts with eculizumab prophylaxis. In group B, 5 subjects had the CFHR31-5::CFHR410 hybrid gene and one had 4 copies of CFHR1 and CFHR4. Compared with group A, patients in group B exhibited a higher prevalence of additional complement abnormalities and earlier disease onset. However, 4/6 patients in this group underwent complete remission without eculizumab treatment. In secondary forms we identified uncommon SVs in 2 out of 92 patients: the CFHR31-5::CFHR410 hybrid and a new internal duplication of CFH.DiscussionIn conclusion, these data highlight that uncommon CFH-CFHR SVs are frequent in primary aHUS and quite rare in secondary forms. Notably, genomic rearrangements involving the CFH are associated with a poor prognosis but carriers respond to anti-complement therapy.
Association between genetically predicted leukocyte telomere length and non-scarring alopecia: A two-sample Mendelian randomization study
Authors: Li Yicheng , Yang Shuting , Liao Minjun , Zheng Zijun , Li Mengyao , Wei Xuerong , Liu Mengqian , Yang Lei 
Published: January 2023

BackgroundThe most commonly acknowledged non-scarring alopecia are androgenetic alopecia (AGA) and alopecia areata (AA). Previous studies have revealed various risk factors associated with alopecia. However, the relationship between leukocyte telomere length (LTL) and non-scarring alopecia remains unclear.MethodsA two-sample Mendelian randomization (MR) analysis was performed to evaluate the causality between genetically predicted LTL and the risk of non-scarring alopecia. MR analyses were performed using the inverse variance-weighted (IVW) method and complemented with other MR methods.ResultsThe summary statistics of the genome-wide association studies (GWAS) for AGA and AA were obtained from the FinnGen biobank, which included 119,185 and 211,428 individuals, respectively. A total of 126 single nucleotide polymorphisms (SNPs) with genome-wide significance were selected as the instrumental variables for LTL. The MR analyses suggested a causal relationship between LTL and AGA, and the risk of AGA increased by 3.19 times as the genetically predicted LTL was shortened by one standard deviation in log transformed form under the IVW method (OR = 4.19, 95% CI = 1.20–14.61, p = 0.024). The other MR methods also demonstrated a similar trend of the effect of LTL on AGA. There was no causal relationship between LTL and AA (p &gt; 0.05). Sensitivity analyses further demonstrated that the current results were less likely to be affected by confounders and bias.ConclusionOur results suggested a potential causal relationship between LTL and AGA, and shortened LTL was associated with an increased risk of AGA.
Clustering and prediction of disease progression trajectories in Huntington's disease: An analysis of Enroll-HD data using a machine learning approach
Authors: Ko Jinnie , Furby Hannah , Ma Xiaoye , Long Jeffrey D. , Lu Xiao-Yu , Slowiejko Diana , Gandhy Rita 
Published: January 2023

IntroductionHuntington's disease (HD) is a rare neurodegenerative disease characterized by cognitive, behavioral and motor symptoms that progressively worsen with time. Cognitive and behavioral signs of HD are generally present in the years prior to a diagnosis; however, manifest HD is typically assessed by genetic confirmation and/or the presence of unequivocal motor symptoms. Nevertheless, there is a large variation in symptom severity and rate of progression among individuals with HD.MethodsIn this retrospective study, longitudinal natural history of disease progression was modeled in individuals with manifest HD from the global, observational Enroll-HD study (NCT01574053). Unsupervised machine learning (k-means; km3d) was used to jointly model clinical and functional disease measures simultaneously over time, based on one-dimensional clustering concordance such that individuals with manifest HD (N = 4,961) were grouped into three clusters: rapid (Cluster A; 25.3%), moderate (Cluster B; 45.5%) and slow (Cluster C; 29.2%) progressors. Features that were considered predictive of disease trajectory were then identified using a supervised machine learning method (XGBoost).ResultsThe cytosine adenine guanine-age product score (a product of age and polyglutamine repeat length) at enrollment was the top predicting feature for cluster assignment, followed by years since symptom onset, medical history of apathy, body mass index at enrollment and age at enrollment.ConclusionsThese results are useful for understanding factors that affect the global rate of decline in HD. Further work is needed to develop prognostic models of HD progression as these could help clinicians with individualized clinical care planning and disease management.
Decreased degree centrality values as a potential neuroimaging biomarker for migraine: A resting-state functional magnetic resonance imaging study and support vector machine analysis
Authors: Wang Qian , Gao Yujun , Zhang Yuandong , Wang Xi , Li Xuying , Lin Hang , Xiong Ling , Huang Chunyan 
Published: January 2023

ObjectiveMisdiagnosis and missed diagnosis of migraine are common in clinical practice. Currently, the pathophysiological mechanism of migraine is not completely known, and its imaging pathological mechanism has rarely been reported. In this study, functional magnetic resonance imaging (fMRI) technology combined with a support vector machine (SVM) was employed to study the imaging pathological mechanism of migraine to improve the diagnostic accuracy of migraine.MethodsWe randomly recruited 28 migraine patients from Taihe Hospital. In addition, 27 healthy controls were randomly recruited through advertisements. All patients had undergone the Migraine Disability Assessment (MIDAS), Headache Impact Test – 6 (HIT-6), and 15 min magnetic resonance scanning. We ran DPABI (RRID: SCR_010501) on MATLAB (RRID: SCR_001622) to preprocess the data and used REST (RRID: SCR_009641) to calculate the degree centrality (DC) value of the brain region and SVM (RRID: SCR_010243) to classify the data.ResultsCompared with the healthy controls (HCs), the DC value of bilateral inferior temporal gyrus (ITG) in patients with migraine was significantly lower and that of left ITG showed a positive linear correlation with MIDAS scores. The SVM results showed that the DC value of left ITG has the potential to be a diagnostic biomarker for imaging, with the highest diagnostic accuracy, sensitivity, and specificity for patients with migraine of 81.82, 85.71, and 77.78%, respectively.ConclusionOur findings demonstrate abnormal DC values in the bilateral ITG among patients with migraine, and the present results provide insights into the neural mechanism of migraines. The abnormal DC values can be used as a potential neuroimaging biomarker for the diagnosis of migraine.
Parent artery occlusion for ruptured aneurysms in moyamoya vessels or on collaterals
Authors: Zhou Zibo , Xu Kan , Yu Jinlu 
Published: January 2023

BackgroundAneurysms in moyamoya vessels or on collaterals are difficult to treat. Parent artery occlusion (PAO) via endovascular treatment (EVT) is often the last resort, but the safety and efficacy of this approach need to be evaluated.Materials and methodsA retrospective study was performed on patients admitted to our hospital who were diagnosed with unilateral or bilateral moyamoya disease (MMD) associated with ruptured aneurysms in moyamoya vessels or on collaterals. These aneurysms were treated with PAO, and the clinical outcome was recorded.ResultsEleven patients were aged 54.7 ± 10.4 years, and six patients were male (54.5%, 6/11). The aneurysms in 11 patients were single and ruptured, and the average size was 2.7 ± 0.6 mm. Three (27.3%, 3/11) aneurysms were located at the distal anterior choroidal artery, 3 (27.3%, 3/11) were at the distal lenticulostriate artery, 3 (27.3%, 3/11) were at the P2–3 segment of the posterior cerebral artery, 1 (9.1%, 1/11) was at the P4–5 segment of the posterior cerebral artery, and 1 was at the transdural location of the middle meningeal artery. Among the 11 aneurysms, PAO by coiling was performed on 7 (63.6%, 7/11), and Onyx casting was performed on 4 (36.4%, 4/11). Of 11 patients, 2 (18.2%, 2/11) suffered intraoperative hemorrhagic complications. During follow-up, all patients had good outcomes with a modified Rankin scale score of 0–2.ConclusionAs a last resort, the application of PAO with coiling or casting Onyx for ruptured aneurysms in moyamoya vessels or on collaterals may be safe with an acceptable clinical outcome. However, patients with MMD may not always achieve expected health outcomes, and PAO for the aneurysm can bring only temporary relief.
Triglyceride glucose index and poor sleep patterns in non-diabetic adults: Evidence from NHANES 2005–2016
Authors: Liu Chi-Feng , Chien Li-Wei 
Published: January 2023

IntroductionSleep disorders are commonly encountered in modern populations. This cross-sectional study aimed to investigate the associations between triglyceride glucose (TyG) index and poor sleep patterns in non-diabetic adults.MethodsData of non-diabetic adults aged 20–70 years were extracted from the US National Health and Nutrition Examination Survey database 2005–2016. Pregnant women, individuals with diabetes and cancer history, and individuals lacking complete data on sleep patterns or parameters for calculating TyG index were excluded. Poor sleep pattern was defined as having two or more following conditions: (1) abnormal sleep duration, defined as less than 7 h or longer than 9 h; (2) self-reported trouble sleeping; and (3) physician-confirmed sleep disorders. Associations between poor sleep patterns, TyG index, and an additional index incorporating body mass index (BMI), TyGBMI, and other study variables were determined by univariable and multivariable logistic regression analysis.ResultsAmong 9,390 included participants, 1,422 had poor sleep patterns and 7,968 did not. The individuals with poor sleep patterns had a higher mean TyG index, were older, had higher BMI, and had higher proportions of hypertension and history of CVD than those without poor sleep pattern (all p &lt; 0.001). Multivariable analysis showed no significant association between poor sleep pattern and TyG index. However, among the components of poor sleep pattern, TyG index in the highest quartile (Q4) was significantly associated with trouble sleeping [adjusted OR (aOR): 1.46, 95%CI: 1.04–2.03) as compared with the lowest TyG quartile (Q1). In addition, TyG-BMI in Q4 was indepently associated with increased likelihood for poor sleep patterns (aOR: 2.18, 95%CI: 1.61–2.95), trouble sleeping (aOR: 1.76, 95%CI: 1.30–2.39), abnormal sleep duration (aOR: 1.41, 95%CI: 1.12–1.78), and sleep disorders (aOR: 3.11, 95%CI: 2.08–4.64) as compared to Q1.DiscussionAmong US adults without diabetes, elevated TyG index is correlated with self-reported trouble sleeping, independent of BMI. Future studies should build upon this preliminary work and examine these associations longitudinally and through treatment trials.
Combining prognostic nutritional index (PNI) and controlling nutritional status (CONUT) score as a valuable prognostic factor for overall survival in patients with stage I–III colorectal cancer
Authors: Kim Harin , Shin Dong-Min , Lee Jae-Hoon , Cho Eun-Suk , Lee Hye Sun , Shin Su-Jin , Park Eun Jung , Baik Seung Hyuk , Lee Kang Young , Kang Jeonghyun 
Published: January 2023

Background and aimsThis study compared the prognostic significance of various nutritional and inflammatory indicators such as neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio and platelet-to-lymphocyte ratio, prognostic nutritional index, and controlling nutritional status score. In addition, we aimed to establish a more accurate prognostic indicator.MethodsWe retrospectively evaluated 1112 patients with stage I–III colorectal cancer between January 2004 and April 2014. The controlling nutritional status scores were classified as low (0–1), intermediate (2–4), and high (5–12) scores. The cut-off values for prognostic nutritional index and inflammatory markers were calculated using the X-tile program. P-CONUT, a combination of prognostic nutritional index and the controlling nutritional status score, was suggested. The integrated areas under the curve were then compared.ResultsThe multivariable analysis showed that prognostic nutritional index was an independent prognostic factor for overall survival, whereas the controlling nutritional status score, neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio were not. The patients were divided into three P-CONUT groups as follows: G1, controlling nutritional status (0–4) and high prognostic nutritional index; G2, controlling nutritional status (0–4) and low prognostic nutritional index; and G3, controlling nutritional status (5–12) and low prognostic nutritional index. There were significant survival differences between the P-CONUT groups (5-year overall survival of G1, G2, and G3 were 91.7%, 81.2%, and 64.1%, respectively; p &lt; 0.0001). The integrated areas under the curve of P-CONUT (0.610, CI: 0.578–0.642) was superior to those of the controlling nutritional status score alone (bootstrap integrated areas under the curve mean difference=0.050; 95% CI=0.022–0.079) and prognostic nutritional index alone (bootstrap integrated areas under the curve mean difference=0.012; 95% CI=0.001–0.025).ConclusionPrognostic effect of P-CONUT may be better than inflammatory markers such as neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio and platelet-to-lymphocyte ratio. Thus, it could be used as a reliable nutritional risk stratification tool in patients with colorectal cancer.
First-line programmed death-1 inhibitor treatment for locoregionally advanced or metastatic cutaneous squamous cell carcinoma – A real-world experience from Israel
Authors: Averbuch Itamar , Salman Saeed , Shtamper Noa , Doweck Ilana , Popovtzer Aron , Markel Gal , Hendler Daniel , Finkel Inbar , Moore Assaf , Fenig Eyal , Taha Tarek , Mhameed Kamel , Kurman Noga , Billan Salem 
Published: January 2023

ObjectiveCutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer worldwide. It is usually treated surgically, with very high cure rates. However, in 3%-7% of cases, cSCC metastasizes to lymph nodes or distant organs. Many of the affected patients are elderly with comorbidities who are not candidates for standard-of-care curative-intent treatment with surgery and/or radio-/chemotherapy. Immune checkpoint inhibitors, which target programmed cell death protein 1 (PD-1) pathways, have recently emerged as a potent therapeutic option. The present report presents the Israeli experience with PD-1 inhibitors for the treatment of loco-regionally advanced or metastatic cSCC in a diverse and elderly population, with or without the addition of radiotherapy.Material and methodsThe databases of two university medical centers were retrospectively searched for patients with cSCC treated with the PD-1 inhibitors cemiplimab or pembrolizumab between January 2019 and May 2022. Data on baseline, disease-related, treatment-related, and outcome parameters were collected and analyzed.ResultsThe cohort included 102 patients of a median age 78.5 years. Evaluable response data were available for 93. The overall response rate was 80.6%: complete response in 42 patients (45.2%) and partial response in 33 (35.5%). Stable disease was recorded in 7 (7.5%) and progressive disease in 11 (11.8%). Median progression-free survival was 29.5 months. Radiotherapy was administered to the target lesion during PD-1 treatment in 22.5% of patients. mPFS was not significantly different in patients who treated with RT than patients how did not (NR vs 18.4 months, HR=0.93, 95%CI: 0.39 - 2.17, p&lt;0.859). Any-grade toxicity was recorded in 57 patients (55%), including grade ‗3 in 25, of whom 5 (5% of cohort) died. Compared to toxicity-free patients, patients with drug toxicity had better progression-free survival (18.4 months vs not reached, HR=0.33, 95% CI: 0.13-0.82, p=0.012) and higher overall response rate (87% vs 71.8%, p=0.06).ConclusionThis retrospective real-world study showed that PD-1 inhibitors were effective in the treatment of locally advanced or metastatic cSCC and appeared to be amenable for use in elderly or fragile patients with comorbidities. However, the high toxicity warrants consideration against other modalities. Induction or consolidation radiotherapy may improve the results. These findings need to be corroborated in a prospective trial.