bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causal association between tea intake and risk for gout: a Mendelian randomization study
Authors: Liang Xiao , Cai Jingjing , Fan Yuchao 
Published: July 2023

Background: Gout, an increasingly prevalent form of inflammatory arthritis, is caused by the accumulation of uric acid crystals in joints, resulting in severe pain, swelling and stiffness that adversely affect physical, mental and emotional wellbeing. The management of gout requires a combination of medication and lifestyle modifications. Recent studies suggest that tea intake may reduce the risk of developing gout; however, further research is needed to establish a causal relationship.Methods: In this study, we employed a bidirectional two-sample Mendelian randomization (MR) approach, utilizing genome-wide association study (GWAS) summary statistics, to investigate the causal association between increased tea intake and gout. We meticulously selected instrumental variables (IVs) based on rigorous criteria and employed five different MR methods. Heterogeneity was assessed using Cochran’s Q statistic, and pleiotropy was evaluated using the MR Egger intercept and MR-PRESSO tests. Weak IVs were identified using F values. The Phenoscanner database was consulted to exclude single nucleotide polymorphisms associated with confounding factors or outcomes.Results: The study included one dataset related to tea intake (ukb-b-6066) and three datasets related to gout (ukb-b-12765, finn-b-M13_GOUT, and finn-b-GOUT_STRICT). Our forward MR analysis suggest a causal relationship between increased tea intake and reduced risk of gout in all three gout-related datasets [OR (95% CI): 0.9966 (0.9938–0.9993), p = 0.0167; 0.4842 (0.2683–0.8737), p-value = 0.0160; and 0.4554 (0.2155–0.9623), p = 0.0393, respectively]. The reveres MR showed increased risk of gout (ukb-b-12765) was significantly associated with low tea intake according to the IVW analysis [OR (95% CI): 0.0062 (0.0002–0.154), p = 0.0020]. However, this association was not observed in the Finn-b-M13_GOUT and Finn-b-GOUT_STRICT [OR (95% CI): 0.9992 (0.9909–1.0075), p = 0.8453 and OR (95% CI): 0.9996 (0.9932–1.0059), p = 0.8896, respectively]. No significant heterogeneity or potential pleiotropy was detected, and the possibility of weak IVs was also excluded.Conclusion: Our MR analysis suggest a causal relationship between genetically predicted tea intake and a decreased risk of gout. These findings underscore the potential advantages of increasing tea intake for preventing gout. However, further research is needed to validate these results and elucidate the underlying mechanisms.
Antibody-dependent cellular cytotoxicity-inducing antibodies enhance the natural killer cell anti-cancer response against patient-derived pancreatic cancer organoids
Authors: Beelen Nicky A. , Aberle Merel R. , Bruno Virginia , Olde Damink Steven W. M. , Bos Gerard M. J. , Rensen Sander S. , Wieten Lotte 
Published: July 2023

IntroductionPancreatic cancer is associated with poor prognosis, and limited treatment options are available for the majority of patients. Natural killer (NK) cells in combination with antibodies inducing antibody-dependent cell-mediated cytotoxicity (ADCC) could be a highly effective new therapeutic option in pancreatic cancer. Accurate predictive preclinical models are needed to develop successful NK cell immunotherapy. Tumor organoids, in vitro 3D organ-like structures that retain important pathophysiological characteristics of the in vivo tumor, may provide such a model. In the current study, we assessed the cytotoxic potential of adoptive NK cells against human pancreatic cancer organoids. We hypothesized that NK cell anti-tumor responses could be enhanced by including ADCC-triggering antibodies.MethodsWe performed cytotoxicity assays with healthy donor-derived IL-2-activated NK cells and pancreatic cancer organoids from four patients. A 3D cytotoxicity assay using live-cell-imaging was developed and enabled real-time assessment of the response.ResultsWe show that NK cells migrate to and target pancreatic cancer organoids, resulting in an increased organoid death, compared to the no NK cell controls (reaching an average fold change from baseline of 2.1±0.8 vs 1.4±0.6). After 24-hours of co-culture, organoid 2D growth increased. Organoids from 2 out of 4 patients were sensitive to NK cells, while organoids from the other two patients were relatively resistant, indicating patient-specific heterogeneity among organoid cultures. The ADCC-inducing antibodies avelumab (anti-PD-L1) and trastuzumab (anti-HER2) increased NK cell-induced organoid cell death (reaching an average fold change from baseline of 3.5±1.0 and 4.5±1.8, respectively). Moreover, combination therapy with avelumab or trastuzumab resulted in complete disintegration of organoids. Finally, inclusion of ADCC-inducing antibodies was able to overcome resistance in NK-organoid combinations with low or no kill.DiscussionThese results support the use of organoids as a relevant and personalized model to study the anti-tumor response of NK cells in vitro and the potential of ADCC-inducing antibodies to enhance NK cell effector function.
Immunoglobulin A levels and its correlation with neutrophil-to-lymphocyte ratio as inflammatory biomarkers for dry eye disease in type 2 diabetes: a retrospective study
Authors: Alhalwani Amani Y. , Abudawood Khulud , Qadizadah Al Baraa Ehab A. , Jambi Shatha , Sannan Naif S. 
Published: July 2023

BackgroundThe neutrophil-to-lymphocyte ratio (NLR) and immunoglobulin A (IgA) level are commonly used as biomarkers for inflammation. Patients with type 2 diabetes (T2D) may experience an imbalance of tear film and inflammation, which can result in dry eye disease (DED). This study aimed to assess the levels of IgA and explore its correlation with the NLR as potential inflammatory biomarkers for dry eye disease in patients with T2D.MethodsA retrospective study was conducted at the cornea clinic and diabetes centre of King Abdulaziz Medical City (Jeddah, Saudi Arabia). The study included patients with DED and the number of available T2D-DED patients determined the sample size. Neutrophil, lymphocyte, IgA and CRP (C-reactive protein) laboratory values were obtained from medical records and correlational analyses were performed.ResultsThe study included 85 patients with an average age of 54 ± 14.4 years for the DED group (n=32) and 62 ± 13.9 years for the T2D-DED group (n=53). The age difference between the two groups was statistically significant (p 0.0001). The NLR values of the T2D-DED and DED groups were 3.203 ± 0.66 and 2.406 ± 0.46, respectively, with no significant difference (p&lt;0.285). Similarly, there were no significant differences in neutrophil and lymphocyte values between the two groups. The IgA levels showed no significant variation between T2D-DED and DED groups (p&lt;0.364). Spearman’s correlation analysis in the DED group showed a significant negative correlation between IgA and lymphocyte (p=0.011; r= - 0.471) values and significant positive correlations between IgA and neutrophil (p=0.014; r=0.309) and NLR (p=0.052; r= - 0.283) values. In the T2D-DED group, a significant correlation was found between IgA and CRP values (p=0.032; r=0.33).ConclusionAlthough diabetic patients may exhibit higher levels of NLR and IgA that correlate with disease severity, our study did not find significant differences in NLR and IgA values between the two groups. These findings may guide future research and enhance understanding of the disease’s underlying mechanisms.
Long term use of eltrombopag in children with chronic immune thrombocytopenia: extended real life retrospective multicenter experience of the Italian Association of Pediatric Hematology and Oncology
Authors: Giordano Paola , Lassandro Giuseppe , Barone Angelica , Cesaro Simone , Fotzi Ilaria , Giona Fiorina , Gorio Chiara , Maggio Angela , Miano Maurizio , Marzollo Antonio , Nardi Margherita , Pession Andrea , Ruggiero Antonio , Russo Giovanna , Saracco Paola , Spinelli Marco , Tolva Alessandra , Tornesello Assunta , Palladino Valentina , Del Vecchio Giovanni Carlo 
Published: July 2023

BackgroundThe present multicenter retrospective study on eltrombopag administration in Italian children with chronic ITP aims to extend follow-up of our previous study.Materials and methodsThis retrospective multicenter study was conducted in 17 centers affiliated to the Italian Association of Pediatric Hematology and Oncology (AIEOP). Patients were classified into three subgroups: group 1 included patients who discontinued treatment due to a stable platelet count; group 2 included patients who discontinued treatment due to ineffectiveness; group 3 included patients who did not permanently discontinue treatment.Results56 patients were eligible for analysis. The median duration of eltrombopag treatment was 40 months (7–71 months). Twenty patients (36%) discontinued permanently eltrombopag. The reasons of permanent discontinuation were adverse effects (n = 1), inefficacy (n = 10), stable platelet count (n = 9). All patients of group 1 maintained a durable response without additional treatments after eltrombopag discontinuation. We found that patients of group 2 were on treatment for less time (median treatment time: 13.5 months, min: 6.0 – max: 56.0) than patients of group 1 (median treatment time: 34 months, min: 16.0 – max: 62.0) (p &lt; 0.05). Patients of group 2 mostly did not achieve a stable platelet count in the first 6 months of treatment and underwent concomitant therapies during follow-up respect of group 1 and group 3 (p &lt; 0.01).ConclusionOur study found that the benefits of eltrombopag treatment, in terms of platelet count improvement and use of additional therapies, are identifiable from the first 6 months of treatment.
Prediction tool for renal adaptation after living kidney donation using interpretable machine learning
Authors: Jeon Junseok , Yu Jae Yong , Song Yeejun , Jung Weon , Lee Kyungho , Lee Jung Eun , Huh Wooseong , Cha Won Chul , Jang Hye Ryoun 
Published: July 2023

IntroductionPost-donation renal outcomes are a crucial issue for living kidney donors considering young donors’ high life expectancy and elderly donors’ comorbidities that affect kidney function. We developed a prediction model for renal adaptation after living kidney donation using interpretable machine learning.MethodsThe study included 823 living kidney donors who underwent nephrectomy in 2009–2020. AutoScore, a machine learning-based score generator, was used to develop a prediction model. Fair and good renal adaptation were defined as post-donation estimated glomerular filtration rate (eGFR) of ≥ 60 mL/min/1.73 m2 and ≥ 65% of the pre-donation values, respectively.ResultsThe mean age was 45.2 years; 51.6% were female. The model included pre-donation demographic and laboratory variables, GFR measured by diethylenetriamine pentaacetate scan, and computed tomography kidney volume/body weight of both kidneys and the remaining kidney. The areas under the receiver operating characteristic curve were 0.846 (95% confidence interval, 0.762–0.930) and 0.626 (0.541–0.712), while the areas under the precision-recall curve were 0.965 (0.944–0.978) and 0.709 (0.647–0.788) for fair and good renal adaptation, respectively. An interactive clinical decision support system was developed.1ConclusionThe prediction tool for post-donation renal adaptation showed good predictive capability and may help clinical decisions through an easy-to-use web-based application.
Long wavelength-sensing cones of zebrafish retina exhibit multiple layers of transcriptional heterogeneity
Authors: Farre Ashley A. , Sun Chi , Starostik Margaret R. , Hunter Samuel S. , English Milton A. , Duncan Audrey , Santhanam Abirami , Shihabeddin Eyad , O’Brien John , Swaroop Anand , Stenkamp Deborah L. 
Published: July 2023

IntroductionUnderstanding how photoreceptor genes are regulated is important for investigating retinal development and disease. While much is known about gene regulation in cones, the mechanism by which tandemly-replicated opsins, such as human long wavelength-sensitive and middle wavelength-sensitive opsins, are differentially regulated remains elusive. In this study, we aimed to further our understanding of transcriptional heterogeneity in cones that express tandemly-replicated opsins and the regulation of such differential expression using zebrafish, which express the tandemly-replicated opsins lws1 and lws2.MethodsWe performed bulk and single cell RNA-Seq of LWS1 and LWS2 cones, evaluated expression patterns of selected genes of interest using multiplex fluorescence in situ hybridization, and used exogenous thyroid hormone (TH) treatments to test selected genes for potential control by thyroid hormone: a potent, endogenous regulator of lws1 and lws2 expression.ResultsOur studies indicate that additional transcriptional differences beyond opsin expression exist between LWS1 and LWS2 cones. Bulk RNA-Seq results showed 95 transcripts enriched in LWS1 cones and 186 transcripts enriched in LWS2 cones (FC &gt; 2, FDR &lt; 0.05). In situ hybridization results also reveal underlying heterogeneity within the lws1- and lws2-expressing populations. This heterogeneity is evident in cones of mature zebrafish, and further heterogeneity is revealed in transcriptional responses to TH treatments.DiscussionWe found some evidence of coordinate regulation of lws opsins and other genes by exogenous TH in LWS1 vs. LWS2 cones, as well as evidence of gene regulation not mediated by TH. The transcriptional differences between LWS1 and LWS2 cones are likely controlled by multiple signals, including TH.
Effects of different transcranial magnetic stimulations on neuropathic pain after spinal cord injury
Authors: Yang Chuanmei , Bi Yunfeng , Hu Luoman , Gong Lili , Li Zhanfei , Zhang Nanyang , Wang Qiang , Li Jiang 
Published: July 2023

IntroductionRepetitive transcranial magnetic stimulation (rTMS) is an effective non-invasive cortical stimulation technique in the treatment of neuropathic pain. As a new rTMS technique, intermittent theta burst stimulation (iTBS) is also effective at relieving pain. We aimed to establish the pain-relieving effectiveness of different modalities on neuropathic pain. The study was conducted in individuals with spinal cord injury (SCI) and different modalities of rTMS.MethodsThirty-seven individuals with SCI were randomly allocated to three groups, in which the “iTBS” group received iTBS, the “rTMS” group received 10 Hz rTMS, and the “iTBS + rTMS” group received iTBS and 10 Hz rTMS successively of the primary motor cortex 5 days a week for 4 weeks, and they all underwent the full procedures. The primary outcome measure was change in the visual analog scale (VAS), and the secondary outcomes were measured using the Hamilton Rating Scale for Depression (HAM-D) and the Pittsburgh Sleep Quality Index (PSQI). All the outcomes were evaluated at 1 day before stimulation (baseline), 1 day after the first week of stimulation (S1), and 1 day after the last stimulation (S2).ResultsThe VAS scores showed significant pain improvement after 4 weeks of stimulation (p = 0.0396, p = 0.0396, and p = 0.0309, respectively) but not after 1 week of stimulation. HAM-D scores declined, but the decreases were not significant until 4 weeks later (p = 0.0444, p = 0.0315, and p = 0.0447, respectively). PSQI scores were also significantly decreased after 4 weeks of stimulation (p = 0.0446, p = 0.0244, and p = 0.0088, respectively). Comparing the three modalities, VAS, HAM-D, and PSQI scores at S1 showed no differences, and, at S2, VAS scores showed significant differences (p = 0.0120; multiple comparisons showed significant differences between iTBS and iTBS + rTMS, p = 0.0091), while the HAM-D and PSQI scores showed no differences.DiscussionThe primary and secondary outcomes all showed significant improvement, indicating that the three different modalities were all effective at relieving the pain. However, not all the three stimulations were of same effectiveness after treatment; there were statistical differences in the treatment of neuropathic pain between iTBS as a priming stimulus and as a single procedure.
Prevalence of neurocognitive disorder in Huntington’s disease using the Enroll-HD dataset
Authors: Sierra Luis A. , Ullman Clementina J. , Baselga-Garriga Clara , Pandeya Sarbesh R. , Frank Samuel A. , Laganiere Simon 
Published: July 2023

BackgroundCognitive decline in Huntington’s disease (HD) begins early in the disease course, however the reported prevalence and severity of cognitive impairment varies based on diagnostic approach. A Movement Disorders Society Task Force recently endorsed the use of standardized DSM-5-based criteria to diagnose neurocognitive disorder (NCD) in Huntington’s disease.ObjectivesTo determine the prevalence and severity of cognitive impairment across different stages of HD by applying NCD criteria (mild and major) to participant data from the Enroll-HD database.MethodsEnroll-HD participants were triaged into either premanifest (preHD), manifest or control groups. PreHD was further dichotomized into preHD near or preHD far based on predicted time to diagnosis using the scaled CAG-age product score (CAPs). Embedded cognitive performance and functional independence measures were used to determine prevalence of NCD (mild and major) for all groups.ResultsPrevalence of NCD-mild was 25.2%–38.4% for manifest HD, 22.8%–47.3% for preHD near, 11.5%–25.1% for preHD far, and 8.8%–19.1% for controls. Prevalence of NCD-major was 21.1%–57.7% for manifest HD, 0.5%–16.3% for preHD near, 0.0%–4.5% for preHD far, and 0.0%–3.0% for controls.ConclusionThe prevalence of NCD in HD is elevated in preHD and demonstrates a sharp rise prior to diagnosis. In manifest HD, the vast majority of participants meet criteria for NCD. These findings are important for optimizing clinical care and/or anticipating the need for supportive services.
Lifelong cerebrovascular disease burden among CADASIL patients: analysis from a global health research network
Authors: Pan Alan P. , Potter Thomas , Bako Abdulaziz , Tannous Jonika , Seshadri Sudha , McCullough Louise D. , Vahidy Farhaan S. 
Published: July 2023

IntroductionData reporting on patients with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) within the United States population is limited. We sought to evaluate the overt cerebrovascular disease burden among patients with CADASIL.MethodsHarmonized electronic medical records were extracted from the TriNetX global health research network. CADASIL patients were identified using diagnostic codes and those with/without history of documented stroke sub-types (ischemic stroke [IS], intracerebral hemorrhage [ICH], subarachnoid hemorrhage [SAH] and transient ischemic attack [TIA]) were compared. Adjusted odds ratios (OR) and 95% confidence intervals (CI) of stroke incidence and mortality associated with sex were computed.ResultsBetween September 2018 and April 2020, 914 CADASIL patients were identified (median [IQR] age: 60 [50–69], 61.3% females); of whom 596 (65.2%) had documented cerebrovascular events (i.e., CADASIL-Stroke patients). Among CADASIL-Stroke patients, 89.4% experienced an IS, co-existing with TIAs in 27.7% and hemorrhagic strokes in 6.2%; initial stroke events occurred ≤65 years of age in 71% of patients. CADASIL-Stroke patients (vs. CADASIL-non-Stroke) had higher cardiovascular and neurological (migraines, cognitive impairment, epilepsy/seizures, mood disorders) burden. In age- and comorbidity-adjusted models, males had higher associated risk of stroke onset (OR: 1.37, CI: 1.01–1.86). Mortality risk was higher for males (OR: 2.72, CI: 1.53–4.84).DiscussionEarly screening and targeted treatment strategies are warranted to help CADASIL patients with symptom management and risk mitigation.
80 Hz auditory steady state responses (ASSR) elicited by silent gaps embedded within a broadband noise
Authors: Kadowaki Seiichi , Morimoto Takashi , Pijanowska Marta , Mori Shuji , Okamoto Hidehiko 
Published: July 2023

IntroductionAlthough auditory temporal processing plays an important role in speech comprehension, it cannot be measured by pure tone audiometry. Auditory temporal resolution is often assessed by behavioral gaps-in-noise test. To evaluate whether auditory temporal resolution could be objectively assessed, we measured the auditory steady state response (ASSR) elicited by silent gaps embedded within broadband noises at 80 Hz.MethodsWe prepared six sound types as test stimuli. One was a continuous broadband noise without a silent interval as a control stimulus and the others were broadband noises with 80 Hz silent intervals of 0.4, 0.8, 1.6, 3.1, and 6.3 ms.ResultsSignificant ASSRs were recorded only when the gap length was longer than the behavioral thresholds and the ASSR amplitude increased as the gap length increased.ConclusionEighty Hertz gap-evoked ASSR appears to reflect the neural activity related to the auditory gap processing and may be used as an objective measure of auditory temporal resolution in humans.
Predictive association of gut microbiome and NLR in anemic low middle-income population of Odisha- a cross-sectional study
Authors: Venugopal Giriprasad , Khan Zaiba Hasan , Dash Rishikesh , Tulsian Vinay , Agrawal Siwani , Rout Sudeshna , Mahajan Preetam , Ramadass Balamurugan 
Published: July 2023

BackgroundIron is abundant on earth but not readily available for colonizing bacteria due to its low solubility in the human body. Hosts and microbiota compete fiercely for iron. &lt;15% Supplemented Iron is absorbed in the small bowel, and the remaining iron is a source of dysbiosis. The gut microbiome signatures to the level of predicting anemia among low-middle-income populations are unknown. The present study was conducted to identify gut microbiome signatures that have predictive potential in association with Neutrophil to lymphocytes ratio (NLR) and Mean corpuscular volume (MCV) in anemia.MethodsOne hundred and four participants between 10 and 70 years were recruited from Odisha’s Low Middle-Income (LMI) rural population. Hematological parameters such as Hemoglobin (HGB), NLR, and MCV were measured, and NLR was categorized using percentiles. The microbiome signatures were analyzed from 61 anemic and 43 non-anemic participants using 16 s rRNA sequencing, followed by the Bioinformatics analysis performed to identify the diversity, correlations, and indicator species. The Multi-Layered Perceptron Neural Network (MLPNN) model were applied to predict anemia.ResultsSignificant microbiome diversity among anemic participants was observed between the lower, middle, and upper Quartile NLR groups. For anemic participants with NLR in the lower quartile, alpha indices indicated bacterial overgrowth, and consistently, we identified R. faecis and B. uniformis were predominating. Using ROC analysis, R. faecis had better distinction (AUC = 0.803) to predict anemia with lower NLR. In contrast, E. biforme and H. parainfluenzae were indicators of the NLR in the middle and upper quartile, respectively. While in Non-anemic participants with low MCV, the bacterial alteration was inversely related to gender. Furthermore, our Multi-Layered Perceptron Neural Network (MLPNN) models also provided 89% accuracy in predicting Anemic or Non-Anemic from the top 20 OTUs, HGB level, NLR, MCV, and indicator species.ConclusionThese findings strongly associate anemic hematological parameters and microbiome. Such predictive association between the gut microbiome and NLR could be further evaluated and utilized to design precision nutrition models and to predict Iron supplementation and dietary intervention responses in both community and clinical settings.