bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ginkgolic acid promotes inflammation and macrophage apoptosis via SUMOylation and NF-κB pathways in sepsis
Authors: Liu Xinyong , Chen Longwang , Zhang Chen , Dong Wei , Liu Hongbing , Xiao Zhong , Wang Kang , Zhang Yaolu , Tang Yahui , Hong Guangliang , Lu Zhongqiu , Zhao Guangju 
Published: January 2023

BackgroundExcessive inflammation and increased apoptosis of macrophages contribute to organ damage and poor prognosis of sepsis. Ginkgolic acid (GA) is a natural constituent extracted from the leaves of Ginkgo biloba, that can regulate inflammation and apoptosis. The present study aims to investigate the potential effect of GA in treating sepsis and its possible mechanisms.Materials and methodsHere, a classic septic mice model and a lipopolysaccharide (LPS)-induced RAW 264.7 inflammation model were established. Cytokines in serum and culture supernatant were detected by ELISA, and the mRNA levels of them were examined by PCR. Hematoxylin and eosin (H&amp;E) staining was performed to determine histopathological changes in liver, lung and kidney. Bacterial burden in the blood, peritoneal lavage fluids (PLFs) and organs were observed on Luria-Bertani agar medium. Flow cytometry and western blotting was used to detect apoptosis and the expression level of apoptosis related molecules, respectively. Moreover, the levels of SUMOylation were detected by western blotting. The activity of NF-κB p65 was assessed by immunofluorescence staining and western blotting.ResultsThe result showed that GA promoted inflammatory responses, reduced bacterial clearance, aggravated organ damage, and increased mortality in septic mice. GA increased apoptosis in peritoneal macrophages (PMs) and RAW 264.7 cells. Meanwhile, GA inhibited SUMOylation and increased the nuclear translocation of NF-κB p65 as well as its phosphorylation level.ConclusionCollectively, GA promotes inflammation and macrophage apoptosis in sepsis, which may be mediated by inhibiting the SUMOylation process and increasing NF-κB p65 activity.
Torque Teno virus DNA is found in the intracranial aneurysm wall—Is there a causative role?
Authors: Rabelo Nícollas Nunes , Yoshikawa Marcia Harumy , Telles João Paulo Mota , Coelho Giselle , de Souza Caio Santos , de Oliveira Natan Ponzoni Galvani , Mendoza Tania Regina Tozetto , Braz-Silva Paulo Henrique , Boechat Antonio Luiz , Teixeira Manoel Jacobsen , Figueiredo Eberval Gadelha 
Published: January 2023

ObjectiveTorque Teno virus (TTV) is a recently discovered virus with high prevalence worldwide, that has been associated with vascular diseases. The aim of this study is to investigate the prevalence of TTV molecular DNA in the intracranial aneurysm (IA) artery walls.MethodSamples of IA walls were collected after microsurgical clipping from 35 patients with IA (22 ruptured/13 unruptured cases). The samples were submitted to molecular DNA extraction using the EasyMag automatized extractor and performed with Qiagen DNA extraction Minikit 250. The samples underwent PCR examination with primers for β-globin as internal control using the Nanodrop® 2000 spectrophotometer. A quantitative (real-time) PCR with TTV-specific primers was performed. Clinical and radiological data of patients included was collected.ResultsTTV was detected in 15 (42.85%) cases, being 10 (45.4%) ruptured and 5 (38.4%) unruptured (p = 0.732) lesions. Multiple IAs accounted for 14 (40%) cases. Five cases (17.2%) had TTV+ and multiple aneurysms (p = 0.73). Association between presence of virus and aneurysm rupture was not statistically significant (p = 0.96).ConclusionThis study demonstrated a relatively high prevalence of viral DNA in the walls of IAs. This is the first study to identify the presence of TTV DNA in IA’s samples, which was found more often in ruptured lesions. This is an exploratory study, therefore, larger studies are required to clarify the relationships between inflammation, viral infection, IA formation and rupture.
Biomechanical changes in the gastrocnemius medius–Achilles tendon complex in people with hypermobility spectrum disorders: A cross-sectional compression sonoelastography study
Authors: Alsiri Najla , Palmer Shea 
Published: January 2023

ObjectiveThis study aimed to assess the biomechanical impact of Hypermobility Spectrum Disorders (HSD) on the elasticity of the gastrocnemius medius-Achilles tendon (GM-AT) complex.MethodsUsing a cross-sectional design, the GM-AT complex elasticity was compared using sonoelastography (SEG) in an HSD group and healthy controls during rest and maximal isometric plantar flexion contraction.ResultsThe HSD group comprised 28 patients (26 women); mean ± SD age 28.7 ± 8.4 years, compared to 28 controls (26 women); 31.5 ± 8.7 years. During rest, greater elasticity was identified in HSD relative to controls at the GM-AT musculotendinous junction (strain ratio 2.05 ± 1.31 vs. 1.48 ± 0.49), mid-AT (3.60 ± 1.97 vs. 2.66 ± 1.00), and distal AT (4.57 ± 2.69 vs. 3.22 ± 1.94) (all p &lt; 0.05). During contraction, no significant differences were found between groups at the GM-AT musculotendinous junction (3.40 ± 2.16 vs. 2.62 ± 1.07), mid AT (10.75 ± 5.29 vs. 8.49 ± 3.53), or distal AT (8.55 ± 5.39 vs. 8.83 ± 3.51) (all p &gt; 0.05). No significant differences were found between groups in the GM strain ratio during rest (4.05 ± 1.43 vs. 3.62 ± 0.78), or contraction (4.23 ± 1.29 vs. 4.19 ± 1.31). Exploratory Receiver Operator Characteristics curve analysis suggested low sensitivity and specificity of the strain ratio for the diagnosis of HSD.ConclusionPeople with HSD have greater GM-AT complex elasticity. Although statistically significant group differences were identified, further research is required to establish the diagnostic, clinical, and research utility of strain ratio measurements.
Assessment of the human placental microbiome in early pregnancy
Authors: Sharlandjieva Vassilena , Beristain Alexander G. , Terry Jefferson 
Published: January 2023

IntroductionBacteria derived from the maternal circulation have been suggested to seed the human placenta during development leading to an intrinsic placental microbiome. This concept has become controversial as numerous studies suggest that the apparent placental microbiome is mostly, if not completely, comprised of contaminants. If the maternal circulation seeds the placenta then there should be an increase in abundance and diversity of detectable bacteria with onset of maternal perfusion of the placenta around 10 weeks gestational age; however, if only contaminants are present then there should be no significant evolution of the placental microbiome with increasing gestational age. This pilot study addresses whether bacterial abundance and diversity increase in human placenta and whether there is an associated shift in the immunophenotype of the decidual immune cell complement before and after initiation of placental perfusion.MethodsHuman placental and decidual tissue from 5 to 19 weeks gestational age, handled aseptically to minimize contamination, is assessed by quantitative 16S polymerase chain reaction (PCR), 16S gene sequencing, and immunological flow cytometry studies.ResultsA weak positive correlation between placental bacterial abundance and gestational age is identified but is not statistically significant. No significant changes in bacterial diversity are found with increasing gestational age. The proportion of decidual activated memory T helper cells increases with gestational age but no change was observed in other lymphocyte subsets.DiscussionThis pilot study does not strongly support bacterial colonization of the placenta after initiation of maternal perfusion; however, the minor trends towards increases in bacterial abundance and activated memory T helper cells may represent an early stage of this process. Additional investigations in larger cohorts are warranted.
New model of superior semicircular canal dehiscence with reversible diagnostic findings characteristic of patients with the disorder
Authors: Wackym P. Ashley , Balaban Carey D. , Van Osch Olivia J. , Morris Brian T. , Tamakloe Mark-Avery , Salvatore Victoria L. , Duwadi Sudan , Gay Jennifer D. , Mowery Todd M. 
Published: January 2023

BackgroundThird window syndrome is a vestibular-cochlear disorder in humans in which a third mobile window of the otic capsule creates changes to the flow of sound pressure energy through the perilymph/endolymph. The nature and location of this third mobile window can occur at many different sites (or multiple sites); however, the most common third mobile window is superior semicircular canal dehiscence (SSCD). There are two essential objective diagnostic characteristics needed to validate a model of SSCD: the creation of a pseudoconductive hearing loss and cVEMP increased amplitude and decreased threshold.MethodsAdult Mongolian gerbils (n = 36) received surgical fenestration of the superior semicircular canal of the left inner ear. ABR and c+VEMP testing were carried out prior to surgery and over acute (small 1 mm SSCD, 1–10 days) or prolonged (large 2 mm SSCD, 28 days) recovery. Because recovery of function occurred quickly, condenser brightfield stereomicroscopic examination of the dehiscence site was carried out for the small SSCD animals post-hoc and compared to both ABRs and c+VEMPs. Micro-CT analysis was also completed with representative samples of control, day 3 and 10 post-SSCD animals.ResultsThe SSCD created a significant worsening of hearing thresholds of the left ear; especially in the lower frequency domain (1–4 kHz). Left (EXP)/right (CTL) ear comparisons via ABR show significant worsening thresholds at the same frequency representations, which is a proxy for the human pseudoconductive hearing loss seen in SSCD. For the c+VEMP measurements, increased amplitude of the sound-induced response (N1 2.5 ms and P1 3.2 ms) was observed in animals that received larger fenestrations. As the bone regrew, the c+VEMP and ABR responses returned toward preoperative values. For small SSCD animals, micro-CT data show that progressive osteoneogenesis results in resurfacing of the SSCD without bony obliteration.ConclusionThe large (2 mm) SSCD used in our gerbil model results in similar electrophysiologic findings observed in patients with SSCD. The changes observed also reverse and return to baseline as the SSCD heals by bone resurfacing (with the lumen intact). Hence, this model does not require a second surgical procedure to plug the SSCD.
Rapid onset of functional tic-like behaviors among adolescent girls—Minnesota, September–November 2021
Authors: Firestone Melanie J. , Holzbauer Stacy , Conelea Christine , Danila Richard , Smith Kirk , Bitsko Rebecca H. , Klammer Susan M. , Gingerich Stefan , Lynfield Ruth 
Published: January 2023

BackgroundOn October 15, 2021, the Minnesota Department of Health began investigating a school cluster of students experiencing tic-like behaviors thought to be related to recent COVID-19. The objective of this report is to describe the investigation, key findings, and public health recommendations.MethodsAffected students and proxies were interviewed with a standardized questionnaire including validated depression and anxiety screens.ResultsEight students had tic-like behaviors lasting &gt;24 h after initial report with onset during September 26–October 30, 2021. All eight students were females aged 15–17 years. All students either had a history of depression or anxiety or scored as having more than minimal anxiety or depression on validated screens. Four students previously had confirmed COVID-19: the interval between prior COVID-19 and tic symptom onset varied from more than a year prior to tic symptom onset to at the time of tic symptom onset.ConclusionThe onset of tic-like behaviors at one school in Minnesota appeared to be related more to underlying mental health conditions than recent COVID-19. These findings highlight the need to better understand functional tic-like behaviors and adolescent mental health.
Explainable artificial intelligence model to predict brain states from fNIRS signals
Authors: Shibu Caleb Jones , Sreedharan Sujesh , Arun KM , Kesavadas Chandrasekharan , Sitaram Ranganatha 
Published: January 2023

Objective: Most Deep Learning (DL) methods for the classification of functional Near-Infrared Spectroscopy (fNIRS) signals do so without explaining which features contribute to the classification of a task or imagery. An explainable artificial intelligence (xAI) system that can decompose the Deep Learning mode’s output onto the input variables for fNIRS signals is described here.Approach: We propose an xAI-fNIRS system that consists of a classification module and an explanation module. The classification module consists of two separately trained sliding window-based classifiers, namely, (i) 1-D Convolutional Neural Network (CNN); and (ii) Long Short-Term Memory (LSTM). The explanation module uses SHAP (SHapley Additive exPlanations) to explain the CNN model’s output in terms of the model’s input.Main results: We observed that the classification module was able to classify two types of datasets: (a) Motor task (MT), acquired from three subjects; and (b) Motor imagery (MI), acquired from 29 subjects, with an accuracy of over 96% for both CNN and LSTM models. The explanation module was able to identify the channels contributing the most to the classification of MI or MT and therefore identify the channel locations and whether they correspond to oxy- or deoxy-hemoglobin levels in those locations.Significance: The xAI-fNIRS system can distinguish between the brain states related to overt and covert motor imagery from fNIRS signals with high classification accuracy and is able to explain the signal features that discriminate between the brain states of interest.
Acute beetroot juice consumption does not alter cerebral autoregulation or cardiovagal baroreflex sensitivity during lower-body negative pressure in healthy adults
Authors: Worley Morgan L. , Reed Emma L. , Chapman Christopher L. , Kueck Paul , Seymour Lauren , Fitts Triniti , Zazulak Hannah , Schlader Zachary J. , Johnson Blair D. 
Published: January 2023

IntroductionBeetroot juice (BRJ) improves peripheral endothelial function and vascular compliance, likely due to increased nitric oxide bioavailability. It is unknown if BRJ alters cerebrovascular function and cardiovagal baroreflex control in healthy individuals.PurposeWe tested the hypotheses that BRJ consumption improves cerebral autoregulation (CA) and cardiovagal baroreflex sensitivity (cBRS) during lower-body negative pressure (LBNP).MethodsThirteen healthy adults (age: 26 ± 4 years; 5 women) performed oscillatory (O-LBNP) and static LBNP (S-LBNP) before (PRE) and 3 h after consuming 500 mL of BRJ (POST). Participants inhaled 3% CO2 (21% O2, 76% N2) during a 5 min baseline and throughout LBNP to attenuate reductions in end-tidal CO2 tension (PETCO2). O-LBNP was conducted at ∼0.02 Hz for six cycles (−70 mmHg), followed by a 3-min recovery before S-LBNP (−40 mmHg) for 7 min. Beat-to-beat middle cerebral artery blood velocity (MCAv) (transcranial Doppler) and blood pressure were continuously recorded. CA was assessed using transfer function analysis to calculate coherence, gain, and phase in the very-low-frequency (VLF; 0.020–0.070 Hz) and low-frequency bands (LF; 0.07–0.20 Hz). cBRS was calculated using the sequence method. Comparisons between POST vs. PRE are reported as mean ± SD.ResultsDuring O-LBNP, coherenceVLF was greater at POST (0.55 ± 0.06 vs. 0.46 ± 0.08; P &lt; 0.01), but phaseVLF (P = 0.17) and gainVLF (P = 0.69) were not different. CoherenceLF and phaseLF were not different, but gainLF was lower at POST (1.03 ± 0.20 vs. 1.12 ± 0.30 cm/s/mmHg; P = 0.05). During S-LBNP, CA was not different in the VLF or LF bands (all P &gt; 0.10). Up-cBRS and Down-cBRS were not different during both LBNP protocols.ConclusionThese preliminary data indicate that CA and cBRS during LBNP in healthy, young adults is largely unaffected by an acute bolus of BRJ.
A meta-analysis suggests the association of reduced serum level of vitamin D and T-allele of Fok1 (rs2228570) polymorphism in the vitamin D receptor gene with celiac disease
Authors: Shree Tanya , Banerjee Pratibha , Senapati Sabyasachi 
Published: January 2023

PurposeAs an immune-modulator, vitamin D is known to regulate immune response and is implicated in disease pathogenesis. Celiac disease (CD) is a systemic autoimmune disease and susceptibility conferred by vitamin D metabolism is under investigation. Studies on the association of vitamin D metabolism and genetic polymorphisms are expected to explain CD pathogenesis. We performed a systematic review–based meta-analysis to investigate the 25(OH)D serum levels and susceptibility conferred by the genetic variants of VDR in CD.MethodsSystematic review was conducted through a web-based literature search following stringent study inclusion–exclusion criteria. The Newcastle–Ottawa Scale and GRADE tools were used to assess the quality of evidence in studies and the study outcome. Cohen's κ value was estimated to access the reviewer's agreement. RevMan 5.4.1 was used to perform the meta-analyses. Weighted mean difference and Meta p-value was assessed for 25(OH)D serum levels. Meta-odds ratio and Z-test p-value were evaluated to estimate the allelic susceptibility of VDR variants.ResultsA total of 8 out of 12 studies were evaluated for “25(OH)D” serum level, while four studies were found eligible for SNPs (Bsm1, Apa1, Fok1, and Taq1) of VDR. Significantly higher levels [WMD = 5.49, p &lt; 0.00001] of 25(OH)D were observed in healthy controls than in patients with CD. rs2228570-T (Fok1) [Meta-OR = 1.52, p = 0.02] was confirmed to be predisposing allele for CD.ConclusionReduced serum level of 25(OH)D and association of Fok1 T-allele of VDR confirmed in this study plays a critical role in immunomodulation and maintaining barrier integrity, which is majorly implicated in CD.
Bilberry-containing supplements on severe dry eye disease in young and middle-aged adults: A 3-month pilot analysis
Authors: Yu Wing Y. , Chan Lily Y. L. , Chung Aden , Lee Paul H. , Woo George C. 
Published: January 2023

PurposeTo explore the effect of bilberry and fish oil combination supplement on a small clinical sample patient-base with severe dry eyes.MethodsTwenty-four subjects were recruited with twelve randomly assigned to the intervention and control groups, respectively. Inclusion criteria included severe dry eye symptoms determined by scores &gt;33 from the Ocular Surface Disease Index (OSDI) questionnaire. The intervention group was instructed to take an oral supplement with key ingredients of 600 mg bilberry extract and 240 mg docosahexaenoic acid-refined fish oil once daily for 3 months. The control group did not take any supplements. Mean changes in OSDI score, non-invasive tear break-up time (NITBUT), phenol red thread test (PRT), and percentage of meibomian gland openings were used as outcome measures. Testing was done at baseline, 1-month, and 3-month follow-up. Comparison between the treatment and control groups, and the younger adult and middle-age groups were performed.ResultsThe mean baseline values for the treatment and control groups were not clinically different. The OSDI score, NITBUT, PRT, and percentage of meibomian gland openings improved after taking the supplements for 3 months. The OSDI score, NITBUT, and PRT showed clinical improvements between the intervention and control groups. These improvements were consistent between the two age groups.ConclusionThis study suggested preliminary improvements in signs and symptoms of severe dry eyes that were independent of age after taking dietary supplementation of bilberry extract and fish oil for 3 months. Further studies using more device-based measures and a placebo supplement are warranted.
A genome-wide association study of germline variation and melanoma prognosis
Authors: Chat Vylyny , Dagayev Sasha , Moran Una , Snuderl Matija , Weber Jeffrey , Ferguson Robert , Osman Iman , Kirchhoff Tomas 
Published: January 2023

BackgroundThe high mortality of cutaneous melanoma (CM) is partly due to unpredictable patterns of disease progression in patients with early-stage lesions. The reliable prediction of advanced disease risk from early-stage CM, is an urgent clinical need, especially given the recent expansion of immune checkpoint inhibitor therapy to the adjuvant setting. In our study, we comprehensively investigated the role of germline variants as CM prognostic markers.MethodsWe performed a genome-wide association analysis in two independent cohorts of N=551 (discovery), and N=550 (validation) early-stage immunotherapy-naïve melanoma patients. A multivariable Cox proportional hazard regression model was used to identify associations with overall survival in the discovery group, followed by a validation analysis. Transcriptomic profiling and survival analysis were used to elucidate the biological relevance of candidate genes associated with CM progression.ResultsWe found two independent associations of germline variants with melanoma prognosis. The alternate alleles of these two SNPs were both associated with an increased risk of death [rs60970102 in MELK: HR=3.14 (2.05–4.81), p=1.48×10-7; and rs77480547 in SH3BP4: HR=3.02 (2.02–4.52), p=7.58×10-8, both in the pooled cohort]. The addition of the combined risk alleles (CRA) of the identified variants into the prognostic model improved the predictive power, as opposed to a model of clinical covariates alone.ConclusionsOur study provides suggestive evidence of novel melanoma germline prognostic markers, implicating two candidate genes: an oncogene MELK and a tumor suppressor SH3BP4, both previously suggested to affect CM progression. Pending further validation, these findings suggest that the genetic factors may improve the prognostic stratification of high-risk early-stage CM patients, and propose putative biological insights for potential therapeutic investigation of these targets to prevent aggressive outcome from early-stage melanoma.