Miracle-dz/UniFAR-FTUs huggingface dataset:
Changing Gears – DBS For Dopaminergic Desensitization in Parkinson's Disease?

In Parkinson's disease, both motor and neuropsychiatric complications unfold as a consequence of both incremental striatal dopaminergic denervation and intensifying long‐term dopaminergic treatment. Together, this leads to ‘dopaminergic sensitization’ steadily increasing motor and behavioral responses to dopaminergic medication that result in the detrimental sequalae of long‐term dopaminergic treatment. We review the clinical presentations of ‘dopaminergic sensitization’, including rebound off and dyskinesia in the motor domain, and neuropsychiatric fluctuations and behavioral addictions with impulse control disorders and dopamine dysregulation syndrome in the neuropsychiatric domain. We summarize state‐of‐the‐art deep brain stimulation, and show that STN‐DBS allows dopaminergic medication to be tapered, thus supporting dopaminergic desensitization. In this framework, we develop our integrated debatable viewpoint of “changing gears”, that is we suggest rethinking earlier use of subthalamic nucleus deep brain stimulation, when the first clinical signs of dopaminergic motor or neuropsychiatric complications emerge over the steadily progressive disease course. In this sense, subthalamic deep brain stimulation may help reduce longitudinal motor and neuropsychiatric symptom expression – importantly, not by neuroprotection but by supporting dopaminergic desensitization through postoperative medication reduction. Therefore, we suggest considering STN‐DBS early enough before patients encounter potentially irreversible psychosocial consequences of dopaminergic complications, but importantly not before a patient shows first clinical signs of dopaminergic complications. We propose to consider neuropsychiatric dopaminergic complications as a new inclusion criterion in addition to established motor criteria, but this concept will require validation in future clinical trials. ANN NEUROL 2021;90:699–710
An investigation into the psychosocial impact of therapeutic recreation summer camp for youth with serious illness and disability

Objectives This study aimed to evaluate the impact on emotional, social, physical and educational functioning of a therapeutic recreation camp provided by ‘Over The Wall’, a UK charity for children and young people with chronic illness or disability. Method Two hundred and sixty four people registered to attend camp were sent the Pediatric Quality of Life Inventory version Child Self-Report Scale before camp, immediately after camp, 1 month after camp and 3 months after camp. Results Of those invited to participate, 178 children completed the pre-camp survey (67% response rate). Of those, 105 completed both the post-camp 1 and pre-camp questionnaires (59% of pre-camp respondents), and 60 of those participants subsequently completed the 1-month post-camp questionnaire as well (34% of pre-camp respondents). Only 32 participants completed the 3-month follow-up data (18% of pre-camp respondents). Across the first three timepoints (pre-Camp, post-Camp and 1 month follow-up), a repeated measures ANOVA indicated a significant improvement in emotional and social functioning, but not physical or school functioning (p < 0.05). Post-hoc analyses on pre-camp and post-camp scores revealed small-medium effect sizes of 0.317 and 0.272 for emotional and social functioning, respectively. Discussion The therapeutic recreation summer camp provided for children and young people with health challenges had a significant, positive impact on emotional and social functioning. Such camps can therefore be considered as having empirical support for their aims. Further work is warranted to increase the response rate to establish the longer term impact of the camps and the wider impact of the camps on the wider family.
Neutrophil Gelatinase-Associated Lipocalin as an Early Predictor of Contrast-Induced Nephropathy Following Endovascular Aortic Repair for Abdominal Aortic Aneurysm

To investigate serum neutrophil gelatinase-associated lipocalin (sNGAL) and urine neutrophil gelatinase-associated lipocalin (uNGAL) as early predictors of contrast-associated acute kidney injury(contrast-induced nephropathy)following endovascular aortic repair for abdominal aortic aneurysm. Prospective cohort study. Subjects included 202 consecutive patients with abdominal aortic aneurysm diagnosed between February 2016 and October 2018. We divided the patients into 2 groups: contrast-induced nephropathy (CIN) (n = 26) and non-CIN (n = 176). We assessed correlations between sNGAL and uNGAL concentrations and standard renal markers at baseline, 6, 24, and 48 hours post-procedure. We constructed conventional receiver operating characteristic (ROC) curves and calculated the area under the curve to assess SCr, eGFR, sNGAL, and uNGAL performance. We derived biomarker cutoff levels from ROC analysis results to maximize sensitivity and specificity values. The CIN incidence within our cohort was 12.9%. sNGAL levels correlated significantly with SCr and eGFR at baseline, 6, and 24 hours post-contrast medium exposure. Similarly, uNGAL levels correlated with SCr and estimated glomerular filtration rate (eGFR) at baseline, 6, and 24 hours post-exposure. sNGAL and uNGAL were significantly elevated as early as 6 hours post-endotherapy in the CIN group; there were only minor changes in the non-CIN group. SCr was also significantly elevated in the CIN group, but not until 48 hours post-catheterization. Both sNGAL and uNGAL may be more accurate than SCr and eGFR as early biomarkers of CIN in patients with abdominal aortic aneurysm undergoing endovascular therapy.
JunD, not c-Jun, is the AP-1 transcription factor required for Ras-induced lung cancer

The AP-1 transcription factor c-Jun is required for Ras-driven tumorigenesis in many tissues and is considered as a classical proto-oncogene. To determine the requirement for c-Jun in a mouse model of K-RasG12D–induced lung adenocarcinoma, we inducibly deleted c-Jun in the adult lung. Surprisingly, we found that inactivation of c-Jun, or mutation of its JNK phosphorylation sites, actually increased lung tumor burden. Mechanistically, we found that protein levels of the Jun family member JunD were increased in the absence of c-Jun. In c-Jun–deficient cells, JunD phosphorylation was increased, and expression of a dominant-active JNKK2-JNK1 transgene further increased lung tumor formation. Strikingly, deletion of JunD completely abolished Ras-driven lung tumorigenesis. This work identifies JunD, not c-Jun, as the crucial substrate of JNK signaling and oncogene required for Ras-induced lung cancer.
The role of repetitive transcranial magnetic stimulation (rTMS) in the treatment of behavioral addictions: Two case reports and review of the literature

Abstract Background Several behaviors, besides consumption of psychoactive substances, produce short-term reward that may lead to persistent aberrant behavior despite adverse consequences. Growing evidence suggests that these behaviors warrant consideration as nonsubstance or “behavioral” addictions, such as pathological gambling, internet gaming disorder and internet addiction. Case presentation Here, we report two cases of behavioral addictions (BA), compulsive sexual behavior disorder for online porn use and internet gaming disorder. A 57-years-old male referred a loss of control over his online pornography use, started 15 years before, while a 21-years-old male university student reported an excessive online gaming activity undermining his academic productivity and social life. Both patients underwent a high-frequency repetitive transcranial magnetic stimulation (rTMS) protocol over the left dorsolateral prefrontal cortex (l-DLPFC) in a multidisciplinary therapeutic setting. A decrease of addictive symptoms and an improvement of executive control were observed in both cases. Discussion Starting from these clinical observations, we provide a systematic review of the literature suggesting that BAs share similar neurobiological mechanisms to those underlying substance use disorders (SUD). Moreover, we discuss whether neurocircuit-based interventions, such as rTMS, might represent a potential effective treatment for BAs.
Impact of glutathione on acute ischemic stroke severity and outcome: possible role of aminothiols redox status

ABSTRACT Objective Acute brain ischemia is accompanied by a disruption of low-molecular-weight aminothiols (LMWTs) homeostasis, such as homocysteine (Hcy), cysteine (Cys), and glutathione (GSH). We investigated the redox balance of LMWTs in blood plasma and its influence on ischemic stroke severity and the functional outcome in patients with an acute period. Patients and methods A total of 177 patients were examined. Total and reduced forms of LMWTs were determined in the first 10–24 h. Stroke severity and functional state were estimated using the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRs) at admission and after 21 days. Results Patients with high levels of total Hcy (> 19 μM) showed significantly reduced redox statuses of all LMWTs. Patients with low total GSH levels (≤ 1.07 μM) were at an increased risk of higher stroke severity (NIHSS > 10) compared to patients with a total GSH level > 2.64 μM (age/gender-adjusted odds ratio: 4.69, 95% CI: 1.43–15.4). Discussion (1) low total GSH level can be considered as a novel risk marker for the severity of acute stroke in conditions of low redox status of LMWTs and (2) high Hcy levels associated with low redox status of LMWTs.
Computational models to delineate 3D gaze-shift strategies in Parkinson’s disease

Objective: Parkinson’s disease (PD) frequently affects vergence eye movements interfering with the perception of depth and dimensionality critical for mitigating falls. We examined neural strategies that compensate for abnormal vergence and their mechanistic underpinning in PD. Approach: The a priori hypothesis was that impaired vergence is compensated by incorporating rapid eye movements (saccades) to accomplish gaze shifts at different depths. Our experiments examined the hypothesis by simulating biologically plausible computational models of saccade-vergence interactions in PD and validating predictions in the actual patient data. Main results: We found four strategies to accomplish 3D gaze shift; pure vergence eye movements, pure saccadic eye movements, combinations of vergence followed by a saccade, and combination of saccade followed by vergence. The gaze shifting strategy of the two eyes was incongruent in PD. The latency of vergence was prolonged, and it was more so when the saccades preceded the vergence or when the saccades only made 3D gaze shift. Computational models predicted at least two possible mechanisms triggering saccades along with vergence. One is based on the lack of foveal accuracy when the vergence gain is suboptimal. The second mechanism reflects the noise in the gating mechanism, the omnipause neurons, for vergence and saccades. None of the two model predictions alone were completely supported by the patient data. However, a combined model incorporating both abnormal vergence velocity gain and impaired gating accurately simulated the results from PD patients. Significance: The combined strategy is biologically plausible for two reasons: (a) The basal ganglia that is prominently affected in PD projects to the vergence velocity neurons in the midbrain via the cerebellum. The projection directly affects the vergence velocity gain. (b) The basal ganglia, via superior colliculus, influences the pattern of omnipause neuronal activity. Abnormal basal ganglia activity may introduce noise in the omnipause neurons.
Doppler abnormalities and perinatal outcomes in pregnant women with early-onset fetal growth restriction

Abstract Objective To compare Doppler alterations and perinatal outcomes in pregnant women who evolved with early- and late-onset fetal growth restriction (FGR). Methods A retrospective, observational cohort study with pregnant women who evolved with FGR treated between January 2018 and April 2019, in which all live births from singleton pregnancies, over 24 weeks, with FGR ultrasound diagnosis and under 2700 g weight were included in the study. Results Pregnancies with early-onset FGR were more associated with hypertensive disorders (p = .00) and placental vascular insufficiency, resulting in a high degree of umbilical artery Doppler involvement (p = .00) in a short period of pregnancy and higher rates of adverse perinatal outcomes (p = .00). The time of prenatal follow-up of early- and late-onset FGR cases was similar, but the degree of prematurity of the former made the evolution more unfavorable. Conclusion Early-onset FGR had a lower prevalence but was associated with higher maternal and fetal morbidity and mortality than late-onset FGR.
Development and validation of a nine-item short screening test for ICD-11 gaming disorder (GAMES test) and estimation of the prevalence in the general young population

Abstract Background and Aims A definition of gaming disorder (GD) was introduced in ICD-11. The purpose of this study was to develop a short screening test for GD, utilizing a reference GD group. It also sought to estimate the prevalence of GD among individuals, representative of the general young population in Japan. Methods Two hundred eighty one men and women selected from the general population, aged between 10 and 29 years, and 44 treatment seekers at our center completed a self-reported questionnaire comprising candidate questions for the screening test. The reference group with ICD-11 GD was established, based on face-to-face interviews with behavioral addiction experts, using a diagnostic interview instrument. The questions in the screening test were selected to best differentiate those who had GD from those who did not, and the cutoff value was determined using the Youden index. Results A nine-item screening test (GAMES test) was developed. The sensitivity and specificity of the test were both 98% and the positive predictive value in the study sample was 91%. The GAMES test comprised two factors, showed high internal consistency and was highly reproducible. The estimated prevalence of GD among the general young population was 7.6% (95% confidence interval; 6.6–8.7%) for males and 2.5% (1.9–3.2%) for females, with a combined prevalence of 5.1% (4.5–5.8%). Discussion and Conclusion The GAMES test shows high validity and reliability for screening of ICD-11 GD. The estimated prevalence of 5.1% among the general young population was comparable to the pooled estimates of young people globally.
Trajectories of mid-life to elderly adulthood BMI and incident hypertension: the China Health and Nutrition Survey

Objectives This study is designed to identify different body mass index (BMI) trajectories of individuals aged 40–70 years and test the effect of distinct BMI trajectories on incident hypertension. Design The accelerated longitudinal design was used for this study. Methods The study drew data from the third to ninth China Health and Nutrition Surveys (CHNS), and 4697 participants were included between 1991 and 2015. As analysed, three distinct individual BMI trajectories were identified by the latent class growth mixed model (LCGMM). Then, BMI values and BMI slopes were worked out through calculation with LCGMM trajectory parameters and their primary derivatives, respectively. Later, Cox proportional hazard models were applied to examine BMI values and slopes, and find out the relationship between the said predicted data and incident hypertension for different classes. Results Three different trajectory classes were identified, that is, low-stable class (n=3711), sharp-increasing class (n=282) and high-stable class (n=704). Compared with the low-stable class, the adjusted HRs (95% CI) were 1.321 (1.119 to 1.559) and 1.504 (1.322 to 1.711) for the sharp-increasing class and the high-stable class, respectively. The HR (95% CI) for BMI values rose from 1.081 (1.030 to 1.135) to 1.221 (1.171 to 1.273) while the HR (95% CI) for BMI slopes dropped from 1.154 (1.100 to 1.211) to 0.983 (0.943 to 1.025). That is, the HR for BMI slopes were higher than that for BMI values for the class aged 40–47 years. Conclusion These findings suggest that the calibrated BMI trajectories for the period from mid-life to elderly adulthood have a significant effect on the risk of incident hypertension. The period from age 40 to 47 years is critical and has positive implications for the early prevention of hypertension.
Cochlear Implantation in Pediatric Patients With Enlarged Vestibular Aqueduct: A Systematic Review

To describe cochlear implantation (CI) outcomes, with speech perception, auditory, language, and parent‐reported auditory and speech behaviors, in children with an enlarged vestibular aqueduct (EVA) and incomplete partition type 2 (IP‐II) and compare to control children without inner ear malformations (IEMs) and to determine cerebrospinal fluid gusher rates and effect on outcomes.
Monocytic differentiation and AHR signaling as Primary Nodes of BET Inhibitor Response in Acute Myeloid Leukemia.

To understand mechanisms of response to BET inhibitors (BETi), we mined the Beat AML functional genomic dataset and performed genome-wide CRISPR screens on BETi- sensitive and BETi- resistant AML cells. Both strategies revealed regulators of monocytic differentiation, SPI1, JUNB, FOS, and aryl-hydrocarbon receptor signaling (AHR/ARNT), as determinants of BETi response. AHR activation synergized with BETi while inhibition antagonized BETi-mediated cytotoxicity. Consistent with BETi sensitivity dependence on monocytic differentiation, ex vivo sensitivity to BETi in primary AML patient samples correlated with higher expression of monocytic markers CSF1R, LILRs, and VCAN. In addition, HL-60 cell line differentiation enhanced its sensitivity to BETi. Further, screens to rescue BETi sensitivity identified BCL2 and CDK6 as druggable vulnerabilities. ¬¬ Finally, monocytic AML patient samples refractory to venetoclax ex vivo were significantly more sensitive to combined BETi + venetoclax. Together, our work highlights mechanisms that could predict BETi response and identifies combination strategies to overcome resistance.
In Situ-DRIFTS Study of Selective Catalytic Reduction of NOx by NH3 over Cu-Exchanged SAPO-34

The intrinsic mechanism of the selective catalytic reduction (SCR) reaction over a Cu-exchanged SAPO-34 catalyst at low temperature was studied by in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), coupled with mass spectrometry to measure inlet and outlet gas concentrations. The evolution of the surface intermediates, as well as the reactivity of NH3 with surface NOx species and NOx with surface NH3 species, was evaluated. In terms of NOx adsorption, surface nitrates and nitrites are the main NOx adsorption species at low temperature. When NO was exposed to the sample with NH3 preadsorbed, surface NH3 was not reactive because of the low surface coverage of nitrates and nitrites. However, the reactivity is significantly enhanced by the inclusion of O2 in the feed, which promotes an increase in the concentration of surface nitrates and nitrites. DRIFTS results also reveal that the low temperature SCR reaction involves the formation of an NH4NO3 intermediate and its subsequent red.
Severe right ventricular hypertrophy in hypertrophic cardiomyopathy: Serious symptoms, complex surgical procedures, and poor prognosis in Fuwai Hospital.

OBJECTIVE Severe right ventricular hypertrophy (SRVH) in hypertrophic cardiomyopathy (HCM) is rare. We studied the clinical characteristics and prognosis of 36 patients with HCM and SRVH in a Chinese cohort. METHODS Patients with HCM and SRVH were enrolled between 2013 and 2017. The clinical characteristics, treatment therapies, and clinical outcomes of the 36 patients were retrospectively studied and compared with those of 128 patients without SRVH. RESULTS Patients in the group with SRVH were younger than those in the group without SRVH (27.58±15.09 years vs 40.34±13.21 years, respectively; p<0.001). Patients with SRVH had more serious clinical symptoms and a higher New York Heart Association functional class than those without SRVH. Most patients in the group with SRVH exhibited diffuse RV hypertrophy, and 13 patients presented with biventricular outflow tract obstruction. Maximal left ventricular (LV) wall thickness (27.29±7.95 mm vs 24.33±5.85 mm, respectively; p=0.027) and LV outflow tract gradient (80.83±24.41 mm Hg vs 42.3±5.7 mm Hg, respectively; p=0.000) were significantly greater in patients with SRVH than in those without SRVH. A total of 30 patients in the group with SRVH underwent surgical correction. During a median follow-up period of 48 months, six patients with SRVH reached primary clinical endpoints (four sudden cardiac deaths, one heart failure-related death, and one heart transplantation), whereas only two deaths occurred in the patients without SRVH. CONCLUSION We conclude that patients with HCM and SRVH exhibit serious symptoms and have complex surgical requirements and poor clinical outcomes.
Comparative Assessment of Wet Torrefaction

Wet torrefaction of typical Norwegian biomass fuels was studied within the temperature window of 175–225 °C, using a benchtop autoclave reactor of 250 mL in volume from Parr Instrument. Two types of local biomass fuels were employed as feedstock, Norway spruce (softwood) and birch (hardwood). Effects of process parameters including pressure, reaction temperature, holding time, and feedstock particle size on the yield and properties of the solid products were investigated. It appears that birch wood is more reactive and produces less solid products than spruce wood in the same wet torrefaction conditions. Increasing pressure above the saturated vapor pressure of water enhances the torrefaction rate. Both reaction temperature and holding time have significant effects on solid product yield and fuel properties of wet torrefied biomass. The yield of solid products is slightly reduced with decreasing feedstock particle size. The ash content of biomass fuel is significantly reduced by wet torrefaction. In addit.