bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Neuroanatomy of Positive Affect Display – Subcortical Fiber Pathways Relevant for Initiation and Modulation of Smiling and Laughing
Authors: Coenen Volker A. , Sajonz Bastian E. A. , Hurwitz Trevor A. , Böck Marlies , Hosp Jonas A. , Reinacher Peter C. , Urbach Horst , Blazhenets Ganna , Meyer Philipp T. , Reisert Marco 
Published: March 2022

BackgroundWe here report two cases of stimulation induced pathological laughter (PL) under thalamic deep brain stimulation (DBS) for essential tremor and interpret the effects based on a modified neuroanatomy of positive affect display (PAD).Objective/HypothesisThe hitherto existing neuroanatomy of PAD can be augmented with recently described parts of the motor medial forebrain bundle (motorMFB). We speculate that a co-stimulation of parts of this fiber structure might lead to a non-volitional modulation of PAD resulting in PL.MethodsWe describe the clinical and individual imaging workup and combine the interpretation with normative diffusion tensor imaging (DTI)-tractography descriptions of motor connections of the ventral tegmental area (VTA) (n = 200 subjects, HCP cohort), [[18F] fluorodeoxyglucose (18FDG)] positron emission tomography (PET), and volume of activated tissue simulations. We integrate these results with literature concerning PAD and the neuroanatomy of smiling and laughing.ResultsDBS electrodes bilaterally co-localized with the MB-pathway (“limiter pathway”). The FDG PET activation pattern allowed to explain pathological PAD. A conceptual revised neuroanatomy of PAD is described.ConclusionEliciting pathological PAD through chronic thalamic DBS is a new finding and has previously not been reported. PAD is evolution driven, hard wired to the brain and realized over previously described branches of the motorMFB. A major relay region is the VTA/mammillary body complex. PAD physiologically undergoes conscious modulation mainly via the MB branch of the motorMFB (limiter). This limiter in our cases is bilaterally disturbed through DBS. The here described anatomy adds to a previously described framework of neuroanatomy of laughter and humor.
Association Between Riboflavin Intake and Telomere Length: A Cross-Sectional Study From National Health and Nutrition Examination Survey 1999–2002
Authors: Chen Weihua , Shi Shanshan , Jiang Yizhou , Chen Liling , Liao Ying , Chen Kaihong , Huang Kun 
Published: March 2022

BackgroundDietary habits and dietary intake affect telomere length, a reliable marker of biological aging and a predictor of chronic disease. Riboflavin (RF) is known as a water-soluble antioxidant vitamin, but its role in telomere length maintenance has yet to be elucidated.ObjectiveThe purpose of this study was to examine the relationship between dietary RF intake and telomere length in a nationally representative sample of adults.MethodsUsing the NHANES (1999–2002), telomere data of 4,298 participants aged ≥45 years were analyzed in a cross-sectional manner. Leukocyte telomere length was measured using the quantitative real-time polymerase chain reaction (qPCR). Dietary RF intake was assessed by a trained interviewer using 24-h dietary recall method. Generalized linear regressions were performed to evaluate the association between dietary RF intake and telomere length. Subgroup analyses were performed to further explore this relationship in sex and body mass index (BMI) subgroups.ResultsAmong the 3,788 participants included, the average telomere length was longer in females (P = 0.014), while they had a lower average RF intake compared to males (P &lt; 0.001). There was a weak positive correlation between RF intake and telomere length both when unadjusted (β = 0.011; P = 0.037) and adjusted for age, sex, and ethnicity (β = 0.013; P = 0.033). Subgroup analyses showed a positive association between RF intake and the telomere length in female after adjusting for confounding factors (β = 0.029; P = 0.046). In the female subgroup, there were significant positive relationships between telomere length and RF intake in the obese group (β = 0.086, P = 0.022).ConclusionIncreased dietary RF intake was significantly associated with longer telomere length in middle-aged and older American females, especially in low RF intake obese female.
New Insights Into a Classification-Based Microvascular Invasion Prediction Model in Hepatocellular Carcinoma: A Multicenter Study
Authors: Xu Wei , Wang Yonggang , Yang Zhanwei , Li Jingdong , Li Ruineng , Liu Fei 
Published: March 2022

Background and AimsMost microvascular invasion (MVI)-predicting models have not considered MVI classification, and thus do not reflect true MVI effects on prognosis of patients with hepatocellular carcinoma (HCC). We aimed to develop a novel MVI-predicting model focused on MVI classification, hoping to provide useful information for clinical treatment strategy decision-making.MethodsA retrospective study was conducted with data from two Chinese medical centers for 800 consecutive patients with HCC (derivation cohort) and 250 matched patients (external validation cohort). MVI-associated variables were identified by ordinal logistic regression. Predictive models were constructed based on multivariate analysis results and validated internally and externally. The models’ discriminative ability and calibration ability were examined.ResultsFour factors associated independently with MVI: tumor diameter, tumor number, serum lactate dehydrogenase (LDH) ≥ 176.58 U/L, and γ-glutamyl transpeptidase (γ-GGT). Area under the curve (AUC)s for our M2, M1, and M0 nomograms were 0.864, 0.648, and 0.782. Internal validation of all three models was confirmed with AUC analyses in D-sets (development datasets) and V-sets (validation datasets) and C-indices for each cohort. GiViTI calibration belt plots and Hosmer-Lemeshow (HL) chi-squared calibration values demonstrated good consistency between observed frequencies and predicted probabilities for the M2 and M0 nomograms. Although the M1 nomogram was well calibrated, its discrimination was poor.ConclusionWe developed and validated MVI prediction models in patients with HCC that differentiate MVI classification and may provide useful guidance for treatment planning.
The Efficacy and Safety of Anlotinib in Pediatric Patients With Refractory or Recurrent Solid Tumors
Authors: Lu Suying , Hong Ye , Chen Huimou , Wu Liuhong , Sun Feifei , Wang Juan , Zhu Jia , Que Yi , Zhang Lian , Zhen Zijun , Sun Xiaofei , Huang Junting , Zhang Yizhuo 
Published: March 2022

Objective: Refractory or recurrent pediatric solid tumors lack effective treatments, and are associated with dismal outcomes. Hence, there is an urgent need for a novel therapeutic strategy. This study aimed to evaluate the efficacy and safety of anlotinib, a novel oral multi-kinase angiogenesis inhibitor, in pediatric patients with refractory or recurrent solid tumors.Methods: This single-institutional, observational retrospective study was conducted in Sun Yat-sen University Cancer Center, China. Refractory or recurrent pediatric solid tumor patients treated with anlotinib between 2018 and 2020 were evaluated.Results: Forty-one and 30 patients were enrolled to evaluate the efficacy and safety of anlotinib, respectively. There was partial response in five patients, stable disease in 22 patients, no patient with complete response, with an objective response ratio of 12.2% (5/41; 95% CI 1.7-22.7). The disease control rate was 65.9% (27/41; 95% CI 50.7-81) and the median progression-free survival was 2.87 months (95% CI 0.86-4.88). The incidence rates of any grade and grade 3–4 adverse events were 80% (24/30) and 23.3% (7/30), respectively. Bleeding (20%, 6/30), hand-foot syndrome (16.7%, 5/30), and diarrhea (13.3%, 4/30) were the most common adverse events. Grade 3–4 adverse events included hypertension, hand-foot syndrome, diarrhea, anemia, and thrombocytopenia. There were no adverse events-related deaths.Conclusion: For heavily pretreated pediatric solid tumors, anlotinib monotherapy and its combination with chemotherapy may be an effective treatment option with tolerable adverse events. It is necessary to monitor blood pressure when using anlotinib in children.
Qinggan Huoxue Recipe Alleviates Alcoholic Liver Injury by Suppressing Endoplasmic Reticulum Stress Through LXR-LPCAT3
Authors: Lu Yifei , Shao Mingmei , Xiang Hongjiao , Wang Junmin , Ji Guang , Wu Tao 
Published: March 2022

Endoplasmic reticulum stress (ERS) plays a key role in alcohol liver injury (ALI). Lysophosphatidylcholine acyltransferase 3 (LPCAT3) is a potential modifier of ERS. It was examined whether the protective effect of Qinggan Huoxue Recipe (QGHXR) against ALI was associated with LPCAT3 by suppressing ERS from in vivo and in vitro experiment. Male C57BL/6 mice were randomly divided into five groups (n = 10, each) and treated for 8 weeks as follows: the control diet-fed group (pair-fed), ethanol diet-fed group (EtOH-fed), QGHXR group (EtOH-fed + QGHXR), Qinggan recipe group (EtOH-fed + QGR), and Huoxue recipe group (EtOH-fed + HXR). QGHXR, QGR, and HXR groups attenuated liver injury mainly manifested in reducing serum ALT, AST, and liver TG and reducing the severity of liver cell necrosis and steatosis in ALI mouse models. QGHXR mainly inhibited the mRNA levels of Lxrα, Perk, Eif2α, and Atf4 and activated the mRNA levels of Lpcat3 and Ire1α, while inhibiting the protein levels of LPCAT3, eIF2α, IRE1α, and XBP1u and activating the protein levels of GRP78 to improve ALI. QGR was more inclined to improve ALI by inhibiting the mRNA levels of Lxrα, Perk, Eif2α, Atif4, and Chop and activating the mRNA levels of Lpcat3 and Ire1α while inhibiting the protein levels of LPCAT3, PERK, eIF2α, IRE1α, and XBP1u. HXR was more inclined to improve ALI by inhibiting the mRNA levels of Perk, Eif2α, Atf4, and Chop mRNA while inhibiting the protein levels of LPCAT3, PERK, eIF2α, IRE1α, and XBP1u and activating the protein levels of GRP78. Ethanol (100 mM) was used to intervene HepG2 and AML12 to establish an ALI cell model and treated by QGHXR-, QGR-, and HXR-medicated serum (100 mg/L). QGHXR, QGR, and HXR groups mainly reduced the serum TG level and the expression of inflammatory factors such as IL-6 and TNF-α in the liver induced by ethanol. In AML12 cells, QGHXR and its disassembly mainly activated Grp78 mRNA expression together with inhibiting Lxrα, Lpcat3, Eif2α, Atf4, and Xbp1 mRNA expression. The protein expression of eIF2α and XBP1u was inhibited, and the expression of PERK and GRP78 was activated to alleviate ALI. In HepG2 cells, QGHXR mainly alleviated ALI by inhibiting the mRNA expression of LPCAT3, CHOP, IRE1α, XBP1, eIF2α, CHOP, and IRE1α protein. QGR was more inclined to inhibit the protein expression of PERK, and HXR was more likely to inhibit the protein expression of ATF4.
Plasma Menthol Glucuronide as a Biomarker for the Behavioral Effects of Menthol and Nicotine in Humans
Authors: Gueorguieva Ralitza , Schwartz Elizabeth K. C. , MacLean R. Ross , DeVito Elise E. , Eid Tore , Wu Ran , O’Malley Stephanie S. , Sofuoglu Mehmet 
Published: March 2022

This secondary analysis sought to determine if plasma menthol glucuronide (MG) concentrations predict changes in three outcomes, subjective drug effects, urges to smoke, and heart rate, following concurrent inhaled menthol and intravenous nicotine. A total of 45 menthol and non-menthol cigarettes smokers (36 male, nine female, 20 Black, and 23 White) were included in this double-blind, placebo-controlled study. Across three test sessions, participants were assigned to a different flavor condition for each session: 0% (no menthol), 0.5%, or 3.2% menthol. In each test session, participants received in a random order one intravenous delivery of saline and two intravenous deliveries of nicotine (0.25 mg/70 kg and 0.5 mg/70 kg), each 1 h apart, concurrent with menthol delivery by e-cigarettes. The main outcomes were subjective drug effects, urges to smoke, and heart rate. The results showed that following e-cigarette inhalation, changes in plasma MG concentrations or “menthol boost” increased proportionally to the menthol concentration in the e-liquids. While changes in plasma MG concentrations were not predictive of increases in heart rate or subjective drug effects that are reflective of acute effects from nicotine (i.e., feel good effects, stimulated, aversive effects), they were predictive of cooling effect, a typical effect of menthol, but only in menthol smokers in the absence of concurrent active nicotine infusion. These findings demonstrate the utility of plasma MG as a biomarker both for acute menthol exposure by e-cigarette inhalation and for the examination of the concentration-dependent behavioral and physiological effects of menthol in humans.
Prevalence and Load of Cervical Ureaplasma Species With Respect to Intra-amniotic Complications in Women With Preterm Prelabor Rupture of Membranes Before 34 weeks
Authors: Kacerovsky Marian , Kukla Rudolf , Bolehovska Radka , Bostik Pavel , Matulova Jana , Mls Jan , Stranik Jaroslav , Jacobsson Bo , Musilova Ivana 
Published: March 2022

Objectives: To determine the prevalence and load of Ureaplasma spp. DNA in the cervical fluid of women with singleton pregnancies complicated by preterm prelabor rupture of membranes (PPROM) with respect to intra-amniotic infection, sterile intra-amniotic inflammation, and colonization of the amniotic fluid.Methods: A total of 217 women with PPROM between gestational ages 24 + 0 and 33 + 6 weeks were included in this study. Paired amniotic and cervical fluid samples were collected at the time of admission via transabdominal amniocentesis and using a Dacron polyester swab, respectively. Microbial invasion of the amniotic cavity was diagnosed using a combination of culture and molecular biology methods. Intra-amniotic inflammation was determined based on the concentration of interleukin-6 in the amniotic fluid. Based on the presence or absence of these conditions, the women were stratified into the following subgroups: intra-amniotic infection (with both), sterile intra-amniotic inflammation (with inflammation only), colonization (with microorganisms only), and negative amniotic fluid (without either). The Ureaplasma spp. DNA load in the cervical fluid was assessed using PCR.Results:Ureaplasma spp. DNA in the cervical fluid was found in 61% (133/217) of the women. Women with negative amniotic had similar prevalence of Ureaplasma spp. DNA in cervical fluid (55%) to those with sterile intra-amniotic inflammation (54%) but lower than those with intra-amniotic infection (73%) and colonization (86%; p &lt; 0.0001). Women with negative amniotic fluid had a lower load of Ureaplasma spp. DNA in their cervical fluid (median: 4.7 × 103 copies of DNA/ml) than those with intra-amniotic infection (median: 2.8 × 105 copies DNA/ml), sterile intra-amniotic inflammation (median: 5.3 × 104 copies DNA/ml), and colonization (median: 1.2 × 105 copies DNA/mL; p &lt; 0.0001).Conclusion: In conclusion, in PPROM at &lt;34 weeks, the presence of intra-amniotic infection, sterile intra-amniotic inflammation, or colonization of the amniotic fluid was associated with a higher prevalence and/or load of Ureaplasma spp. DNA in the cervical fluid than the absence of intra-amniotic complications.
Introduction of the Hezar International Gravity Formula
Authors: Hassanpour Mehdi , Rezaie Mohammad Reza , Khezripour Saeedeh , Faruque Mohammad Rashed Iqbal , Khandaker Mayeen Uddin 
Published: March 2022

The National Cartographic Center of Iran measured the differences in gravity between the Hezar summit and peak of Mount Damavand using a CG-5 gravity meter. The gravity recorded at the Hezar summit (4,499.416 m) was 213 mGal (0.00213 m/s2) lower than the reading recorded at the peak of Mount Damavand (5,605.730 m). Recently, the exact value of gravity at the Hezar summit and peak of Damavand mount have been measured. This study attempts to modify the conventional version of Hezar International Gravity Formula (HIGF) to calculate the experimental gravity in the Earth’s summits and land surfaces. Apart from describing the 213 mGal difference in gravity between Hezar summit and peak of Mount Damavand, HIGF is also in agreement with practical gravity with distance from sea level and latitude (93% confidence level). The results indicated that the experimental HIGF asg =978,031.85(1 + 0.0053024 sin2θ−0.000032309786 sin22θ)−0.27 hwas in agreement with the practical gravity compared to the 1984 International Gravitational Formula (IGF84).
Cooling to Hypothermic Circulatory Arrest by Immersion vs. Cardiopulmonary Bypass (CPB): Worse Outcome After Rewarming in Immersion Cooled Pigs
Authors: Filseth Ole Magnus , Hermansen Stig Eggen , Kondratiev Timofei , Sieck Gary C. , Tveita Torkjel 
Published: March 2022

IntroductionCooling by cardiopulmonary bypass (CPB) to deep hypothermic cardiac arrest (HCA) for cardiac surgical interventions, followed by CPB-rewarming is performed on a routine basis with relatively low mortality. In contrast, victims of deep accidental hypothermia rewarmed with CPB generally have a much worse prognosis. Thus, we have developed an intact pig model to compare effects on perfusion pressures and global oxygen delivery (DO2) during immersion cooling versus cooling by CPB. Further, we compared the effects of CPB-rewarming between groups, to restitute cardiovascular function, brain blood flow, and brain metabolism.Materials and MethodsTotal sixteen healthy, anesthetized juvenile (2–3 months) castrated male pigs were randomized in a prospective, open placebo-controlled experimental study to immersion cooling (IMMc, n = 8), or cooling by CPB (CPBc, n = 8). After 75 minutes of deep HCA in both groups, pigs were rewarmed by CPB. After weaning from CPB surviving animals were observed for 2 h before euthanasia.ResultsSurvival rates at 2 h after completed rewarming were 4 out of 8 in the IMMc group, and 8 out of 8 in the CPBc group. Compared with the CPBc-group, IMMc animals showed significant reduction in DO2, mean arterial pressure (MAP), cerebral perfusion pressure, and blood flow during cooling below 25°C as well as after weaning from CPB after rewarming. After rewarming, brain blood flow returned to control in CPBc animals only, and brain micro dialysate-data showed a significantly increase in the lactate/pyruvate ratio in IMMc vs. CPBc animals.ConclusionOur data indicate that, although global O2 consumption was independent of DO2, regional ischemic damage may have taken place during cooling in the brain of IMMc animals below 25°C. The need for prolonged extracorporeal membrane oxygenation (ECMO) should be considered in all victims of accidental hypothermic arrest that cannot be weaned from CPB immediately after rewarming.
Association of Excessive Sleepiness, Pathological Fatigue, Depression, and Anxiety With Different Severity Levels of Obstructive Sleep Apnea
Authors: Mjelle Karin Elisabeth Sundt , Lehmann Sverre , Saxvig Ingvild West , Gulati Shashi , Bjorvatn Bjørn 
Published: March 2022

ObjectiveThe aim of this study was to investigate possible associations between obstructive sleep apnea and fatigue. This naturally led to considering the association between OSA and excessive sleepiness, depression, and anxiety.BackgroundOSA is a highly prevalent sleep disorder, associated with a risk of hypertension, cardiovascular events, daytime sleepiness, poor cognitive function, and sudden death during sleep. Both excessive sleepiness, fatigue, and symptoms of depression are frequently reported.Method5,464 patients referred to a university hospital for obstructive sleep apnea underwent standard respiratory polygraphy. The severity of OSA was defined as either mild, moderate, or severe, using the apnea–hypopnea index. Validated questionnaires were used to assess excessive sleepiness, pathological fatigue, depression, and anxiety.ResultsNearly 70% of the patients were men, and median age was 50 (range: 16–89) years. One in three had moderate-to-severe OSA (AHI ≥ 15). Excessive sleepiness and pathological fatigue were present in 43 and 39%, respectively. The prevalence of possible depression and anxiety was 19 and 28%, respectively. The proportion of patients with male sex, obesity, and excessive sleepiness increased with the severity of OSA. In contrast, the proportion of patients with pathological fatigue did not increase with OSA severity, and there was a decrease in depression and anxiety with increasing OSA severity.ConclusionOur study reports that pathological fatigue, as well as anxiety and depression, did not increase with OSA severity, whereas excessive sleepiness did. Knowledge concerning conditions related to OSA severity may be indicative of pretest probability of OSA and thus change the priority for polygraphy. Furthermore, the high prevalence rates of fatigue, anxiety, and depression among these patients warrant further investigations.
The Psychometric Properties of the French–Canadian Stress and Anxiety to Viral Epidemics-6 Scale for Measuring the Viral Anxiety of the General Population During the COVID-19 Pandemic
Authors: Park C. Hyung Keun , Ahmed Oli , Lee Sangha , Suh Sooyeon , Chung Seockhoon , Gouin Jean-Philippe 
Published: March 2022

ObjectiveThis study examined the psychometric properties of the French–Canadian version of the Stress and Anxiety to Viral Epidemics-6 items (SAVE-6) scale for assessing the anxiety response to the viral epidemic among the general population in Quebec, Canada.MethodsA total of 590 participants responded to a confidential online survey between September 28 and October 18, 2020. Confirmatory Factor Analysis (CFA) was conducted to explore the factor structure of the scale. Psychometric properties were assessed using the Item Response Theory (IRT) approach. To explore the convergent validity, a Pearson correlation analysis between the SAVE-6 scale and the depression (Patient Health Questionnaire-2, PHQ-2) or anxiety subscale (Generalized Anxiety Disorder-2, GAD-2) of the Patient Health Questionnaire-4 items scale was conducted.FindingsThe French–Canadian version of the SAVE-6 scale was clustered into a single factor. The CFA of the SAVE-6 scale showed a good model fit (CFI = 0.985, TLI = 0.976, RMSEA = 0.051, RSMR = 0.048), and the multi-group CFA revealed that the SAVE-6 scale can measure anxiety response in the same way across gender or the presence of elevated depressive and anxiety symptoms. It showed good internal consistency (Cronbach's alpha = 0.76, McDonald's Omega = 0.77) and significant correlation with the PHQ-2 score and GAD-2 score. The IRT model suggested the efficiency in discrimination among individuals in this latent trait.ConclusionThe French–Canadian version of the SAVE-6 scale is a valid and reliable rating scale, which can measure the general population's anxiety response to the viral epidemic.