Miracle-dz/UniFAR-FTUs huggingface dataset:
From thought to action: On the relevance of including situational cues in thought about intended actions

Successful everyday self-regulation often hinges on implementing intended responses at a later time–often in specific situations. We address this self-regulation challenge by examining the role of individuals’ thought about intended actions–and specifically whether it does or does not include situational cues. We hypothesized that including situational cues when thinking about intended actions enables stimulus-response learning, thereby increasing the likelihood of implementing the intended actions. Consequently, we pre-registered and found (N = 392, age range 18–94) a positive relationship between the self-reported habitual inclusion of situational cues in thought about intended actions and everyday self-regulation success (assessed by self-reported self-efficacy and self-control beliefs). In addition, we provide exploratory evidence that the inclusion of situational cues in thought about intended actions mediates the relationship between conscientiousness and self-regulation success. We discuss the results and the theoretical perspective in relation to how self-control outcomes can be explained by associative learning.
Slowly evolving dopaminergic activity modulates the moment-to-moment probability of reward-related self-timed movements

Clues from human movement disorders have long suggested that the neurotransmitter dopamine plays a role in motor control, but how the endogenous dopaminergic system influences movement is unknown. Here, we examined the relationship between dopaminergic signaling and the timing of reward-related movements in mice. Animals were trained to initiate licking after a self-timed interval following a start-timing cue; reward was delivered in response to movements initiated after a criterion time. The movement time was variable from trial-to-trial, as expected from previous studies. Surprisingly, dopaminergic signals ramped-up over seconds between the start-timing cue and the self-timed movement, with variable dynamics that predicted the movement/reward time on single trials. Steeply rising signals preceded early lick-initiation, whereas slowly rising signals preceded later initiation. Higher baseline signals also predicted earlier self-timed movements. Optogenetic activation of dopamine neurons during self-timing did not trigger immediate movements, but rather caused systematic early-shifting of movement initiation, whereas inhibition caused late-shifting, as if modulating the probability of movement. Consistent with this view, the dynamics of the endogenous dopaminergic signals quantitatively predicted the moment-by-moment probability of movement initiation on single trials. We propose that ramping dopaminergic signals, likely encoding dynamic reward expectation, can modulate the decision of when to move.
Coupling the immunomodulatory properties of the HDAC6 inhibitor ACY241 with Oxaliplatin promotes robust anti-tumor response in non-small cell lung cancer

ABSTRACT While HDAC inhibitors have shown promise in hematologic cancers, their efficacy remains limited in solid cancers. In the present study, we evaluated the immunomodulatory properties of the HDAC6 inhibitor, Citarinostat (ACY241) on lung tumor immune compartment and its therapeutic potential in combination with Oxaliplatin. As a single agent, ACY241 treatment promoted increased infiltration, activation, proliferation, and effector function of T cells in the tumors of lung adenocarcinoma-bearing mice. Furthermore, tumor-associated macrophages exhibited downregulated expression of inhibitory ligands in favor of increased MHC and co-stimulatory molecules in addition to higher expression of CCL4 that favored increased T cell numbers in the tumors. RNA-sequencing of tumor-associated T cells and macrophages after ACY241 treatment revealed significant genomic changes that is consistent with improved T cell viability, reduced inhibitory molecular signature, and enhancement of macrophage capacity for improved T cell priming. Finally, coupling these ACY241-mediated effects with the chemotherapy drug Oxaliplatin led to significantly enhanced tumor-associated T cell effector functionality in lung cancer-bearing mice and in patient-derived tumors. Collectively, our studies highlight the molecular underpinnings of the expansive immunomodulatory activity of ACY241 and supports its suitability as a partner agent in combination with rationally selected chemotherapy agents for therapeutic intervention in NSCLC.
Pregnancy resumption following contraceptive discontinuation: Hazard survival analysis of the Indonesia Demographic and Health Survey Data 2007, 2012 and 2017

Objective The objective of this research is to estimate the probability of pregnancy resumption after discontinuing reversible contraceptives—pills, injectables, implants and IUDs, and to examine the factors associated with the resumption of fertility. Method The study uses pregnancy calendar data from Indonesia Demographic and Health Surveys (IDHS) of 2007, 2012 and 2017. A hazard model survival method is used for estimating the time needed to resume pregnancy since discontinuing reversible contraceptives. Retrospective data on 4,573; 5,183 and 5,989 episodes of reversible contraceptive discontinuation at the three surveys respectively have been analysed. Results This study shows that women regained fecundity within one year of discontinuing IUD, pill, injectables or implants. Women using IUD could resume their pregnancy faster than those using implants, pills and injectables. Over the three IDHS 2007, 2012 and 2017 the age-specific percentages of women becoming pregnant after one year of contraceptive discontinuation vary between 72 and 85 for IUD, 75 and 81 for pills, 72 and 76 for implants and 64 and 67 for injectables, with the percentages being higher among younger women. The analysis further shows that length of contraceptive use, parity, prior sexually transmitted infections, knowledge of fertile period, household wealth status and place of residence have no impact on occurrence of pregnancy after contraceptive discontinuation. Conclusion The analysis disproves a myth that reversible contraceptives make women infertile. Depending on the type of reversible contraceptive used, 65% to 85% of the women were able to conceive after one year of discontinuation.
NCAPG is a prognostic biomarker of immune infiltration in non-small-cell lung cancer.

Purpose: Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related deaths. The protein NCAPG plays a significant role in tumor development. Patients & methods: We set up a tissue microarray (containing 140 NSCLC and ten normal lung tissues) and performed immunohistochemistry to assess NCAPG expression in the tissues of 140 patients. The prognostic value of NCAPG in NSCLC was assessed using the univariate and multivariate Cox proportional hazards regression models and Kaplan-Meier plots. We analyzed the association between NCAPG and immune infiltration in NSCLC. Results: Multifactorial analysis and Kaplan-Meier plots revealed that upregulation of NCAPG expression was an independent factor in the prognosis of NSCLC. Data from CIBERSORT showed a negative correlation between NCAPG and the expression of memory CD4+ T cells, CD8+ T cells, dendritic cells, macrophages, mast cells and natural killer cells (p < 0.001). Gene set enrichment analysis revealed that cell cycle, adhesion and proliferation were significantly enriched in samples with a high NCAPG expression. Conclusion: NCAPG is a novel biomarker of prognosis and is associated with immune cell infiltration in the tumor microenvironment. Thus it may be a potential target in NSCLC treatment.
Classification of Caenorhabditis Elegans Locomotion Behaviors With Eigenfeature-Enhanced Long Short-Term Memory Networks

The free-living nematode Caenorhabditis elegans is an ideal model for understanding behavior and networks of neurons. Experimental and quantitative analyses of neural circuits and behavior have led to system-level understanding of behavioral genetics and process of transformation from sensory integration in stimulus environments to behavioral outcomes. The ability to differentiate locomotion behavior between wild-type and mutant Caenorhabditis elegans strains allows precise inference on and gaining insights into genetic and environmental influences on behaviors. This paper presents an eigenfeature-enhanced deep-learning method for classifying the dynamics of locomotion behavior of wild-type and mutant Caenorhabditis elegans. Classification results obtained from public benchmark time-series data of eigenworms illustrate the superior performance of the new method over several existing classifiers. The proposed method has potential as a useful artificial-intelligence tool for automated identification of the nematode worm behavioral patterns aiming at elucidating molecular and genetic mechanisms that control the nervous system.
A Remote Questionnaire-Based Study to Compare Alcohol Use in 1030 Final-Year High School Students in Split-Dalmatia County, Croatia Before and During the National Lockdown Due to the COVID-19 Pandemic

Background The COVID-19 pandemic affected drinking behaviors among adolescents. This remote questionnaire-based study aimed to compare alcohol use in 1030 final-year high school students in Split-Dalmatia County (SDC), Croatia before and during the national lockdown due to the COVID-19 pandemic. Material/Methods An online self-reported questionnaire survey was conducted among 1030 final-year high school students (57.96% female; mean age 17.71 years, SD=0.66) in SDC. The data were collected from June 6 to July 20, 2020 and from October 12 to December 28, 2020. Differences in drinking habits between groups were detected with the chi-squared (χ2) test and before and during the COVID-19 lockdown using the Z test. Results Before the lockdown, 84.66% of students were consuming alcohol, most frequently with friends (78.64%) and “to feel better” (29.51%), while during the lockdown, 44.76% of them were drinking, most frequently with friends (34.37%) and due to boredom (17.48%). Drinking alone (P=0.005) and with family members (P=0.003) significantly increased during the lockdown. No difference in drinking between girls and boys was found before the lockdown, but boys were drinking more during the lockdown (P<0.001). There was no difference in drinking prevalence in different schools before the lockdown, but during the lockdown, more students from vocational schools were drinking (P<0.001) and with higher frequency (P=0.002). Among 53.98% of students during the lockdown, a reduction in frequency of drinking was found (P<0.001), most significantly on islands (P=0.05). Conclusions During the lockdown due to the COVID-19 pandemic, alcohol consumption by final-year high school students in SDC significantly decreased, particularly in girls and in gymnasium/private school students.
Clinical outcomes of slow-coagulation continuous-wave transscleral cyclophotocoagulation laser for treatment of glaucoma

Purpose of review The complications and inadequate efficacy of prior cyclodestructive procedures limited their role in glaucoma management. Recent advances in treatment techniques and parameters for laser cyclophotocoagulation has expanded its role in today's glaucoma practice. In this review, we discuss the treatment outcomes of slow-coagulation continuous-wave transscleral cyclophotocoagulation (CW-TSCPC) as a glaucoma surgical procedure for multiple types of glaucoma in lowering intraocular pressure (IOP). Recent findings Slow-coagulation TSCPC is a relatively new technique for CW-TSCPC that, unlike the ‘pop’ power titration technique of laser energy delivery, aims to avoid the production of the ‘pop’ sound that signals explosive inflammatory energy delivery to the ciliary body and nearby tissue. In slow-coagulation TSCPC, laser energy is applied in a fixed and lower amount over a longer duration, compared with the conventional pop technique. This laser energy approach leads to more stable, reliable, titratable, and selective ciliary body ablation for control of IOP, especially relative to the controversial current use of micropulse TSCPC. Summary Slow-coagulation CW-TSCPC can be used safely, efficiently, reproducibly, and efficaciously in wide range of glaucoma types including those with no history of incisional surgeries, good visual acuity, and medically refractory glaucomas.
Gamma frequency light flicker regulates amyloid precursor protein trafficking for reducing β‐amyloid load in Alzheimer's disease model

Inducing gamma oscillations with non‐invasive light flicker has been reported to impact Alzheimer's disease‐related pathology. However, it is unclear which signaling pathways are involved in reducing amyloid load. Here, we found that gamma frequency light flicker increased anchoring of amyloid precursor protein (APP) to the plasma membrane for non‐amyloidogenic processing, and then physically interacted with KCC2, a neuron‐specific K+‐Cl− cotransporter, suggesting that it is essential to maintain surface GABAA receptor α1 levels and reduce β‐amyloid (Aβ) production. Stimulation with such light flicker limited KCC2 internalization and subsequent degradation via both tyrosine phosphorylation and ubiquitination, leading to an increase in surface‐KCC2 levels. Specifically, PKC‐dependent phosphorylation of APP on a serine residue was induced by gamma frequency light flicker, which was responsible for maintaining plasma membrane levels of full‐length APP, leading to its reduced trafficking to endosomes and inhibiting the β‐secretase cleavage pathway. The activated PKC from the gamma frequency light flicker subsequently phosphorylated serine of KCC2 and stabilized it onto the cell surface, which contributed to the upregulation of surface GABAA receptor α1 levels. Together, these data indicate that enhancement of APP trafficking to the plasma membrane via light flicker plays a critical modulatory role in reduction of Aβ load in Alzheimer's disease.
A versatile hydrogel network–repairing strategy achieved by the covalent-like hydrogen bond interaction

Hydrogen bond engineering is widely exploited to impart stretchability, toughness, and self-healing capability to hydrogels. However, the enhancement effect of conventional hydrogen bonds is severely limited by their weak interaction strength. In nature, some organisms tolerate extreme conditions due to the strong hydrogen bond interactions induced by trehalose. Here, we report a trehalose network–repairing strategy achieved by the covalent-like hydrogen bonding interactions to improve the hydrogels’ mechanical properties while simultaneously enabling them to tolerate extreme environmental conditions and retain synthetic simplicity, which proves to be useful for various kinds of hydrogels. The mechanical properties of trehalose-modified hydrogels including strength, stretchability, and fracture toughness are substantially enhanced under a wide range of temperatures. After dehydration, the modified hydrogels maintain their hyperelasticity and functions, while the unmodified hydrogels collapse. This strategy provides a versatile methodology for synthesizing extremotolerant, highly stretchable, and tough hydrogels, which expand their potential applications to various conditions.
The Edmonton Obesity Staging System and pregnancy outcomes in women with overweight or obesity: A secondary analysis of a randomized controlled trial

The Edmonton Obesity Staging System (EOSS) is a proposed clinical practice tool to determine obesity severity. In a secondary analysis of the Pregnancy Exercise and Research Study (PEARS) (a mobile‐health‐supported lifestyle intervention among pregnant women with body mass index [BMI] ≥25 kg/m2), we apply the EOSS and explore relationships with pregnancy outcomes. In early (14–16 weeks) and late (28 weeks) pregnancy, fasting lipids and glucose were measured, blood pressure was extracted from medical records and maternal well‐being was assessed using the WHO‐5 Well‐being Index. Pearson's correlations, chi‐square statistics and multiple logistic regression were used to identify relationships. One‐way analysis of variance was used to compare groups. Pregnant women (n = 348) were mean (SD) age 32.44 (4.39) years and median (interquartile range) BMI 28.0 (26.57, 29.88) kg/m2. Using metabolic criteria only, 81.9% and 98.9% had raised EOSS scores in early and late pregnancy. From early to late pregnancy, EOSS scores increased by 60.1%. Of these, 10.5% experienced a 2‐point increase, moving from stage 0 to stage 2. There was a potential relationship between early EOSS and large for gestational age (χ2 = 6.42, df (2), p = . 04), although significance was lost when controlled for confounders (p = .223) and multiple testing. Most women with BMI ≥25 kg/m2 had raised EOSS scores, limiting the clinical utility of the tool.
Predictors of cognitive and emotional symptoms 12 months after first-ever mild stroke

ABSTRACT Even mild strokes may affect the patients’ everyday life by impairing cognitive and emotional functions. Our aim was to study predictors of such impairments one year after first-ever mild stroke. We included cognitively healthy patients ≤ 70 years with acute mild stroke. Vascular risk factors, sociodemographic factors and stroke classifications were recorded. At one-year post-stroke, different domains related to cognitive and emotional function were assessed with validated instruments. Logistic regression analyses were performed to identify predictors of cognitive and emotional outcome. Of 117 patient assessed at follow-up, only 21 patients (18%) scored within the reference range on all cognitive and emotional assessments. Younger age, multiple infarcts, and being outside working life at stroke onset were independent predictors of cognitive impairments (psychomotor speed, attention, executive and visuospatial function, memory). Female gender and a higher National Institutes of Health Stroke Scale (NIHSS) score at discharge were significantly associated with emotional impairments (anxiety, depressive symptoms, fatigue, apathy, emotional lability) after one year, but these associations were only seen in the unadjusted models. In conclusion, patients in working age may profit from a follow-up during the post-stroke period, with extra focus on cognitive and emotional functions.
Electroacupuncture for cervicogenic dizziness with somatosensory pulsatile tinnitus

Cervicogenic dizziness (CGD) is a syndrome of dizziness and disequilibrium associated with neck pain.1 There are no definitive clinical or laboratory tests for CGD, and therefore, it must be a diagnosis of exclusion. Somatosensory pulsatile tinnitus (SSPT) is subgroup of tinnitus characterised by high-pitched, cardiac-synchronous tinnitus, in which pulsations are suppressed by strong contractions or compressions of the neck and jaw muscles (somatic testing). 2 Electroacupuncture (EA) has been found to be effective in the treatment of chronic myofascial pain3,4; however, to our knowledge, it has not previously been reported in the treatment of CGD with SSPT.
Comparative genomics and evolutionary analysis of Lactococcus garvieae isolated from human endocarditis

Lactococcus garvieae is a well-known pathogen of fish, but is rarely involved in infections in humans and other mammals. In humans, the main clinical manifestation of L. garvieae infections is endocarditis usually related to the ingestion of contaminated food, such as undercooked fish and shellfish. This study presents the first complete genomic sequence of a clinical L. garvieae strain isolated from a patient with endocarditis and its comparative analysis with other genomes. This human isolate contains a circular chromosome of 2 099 060 bp and one plasmid of 50 557 bp. In comparison with other fully sequenced L. garvieae strains, the chromosomal DNA of L. garvieae Lg-Granada carries a low proportion of insertion sequence elements and a higher number of putative prophages. Our results show that, in general, L. garvieae is a highly recombinogenic species with an open pangenome in which almost 30 % of its genome has undergone horizontal transfers. Within the genus Lactococcus, L. lactis is the main donor of genetic components to L. garvieae but, taking Lg-Granada as a representative, this bacterium tends to import more genes from Bacilli taxa than from other Lactococcus species.
Positional scanning of natural product hispidol’s ring-B: discovery of highly selective human monoamine oxidase-B inhibitor analogues downregulating neuroinflammation for management of neurodegenerative diseases

Abstract Multifunctional molecules might offer better treatment of complex multifactorial neurological diseases. Monoaminergic pathways dysregulation and neuroinflammation are common convergence points in diverse neurodegenerative and neuropsychiatric disorders. Aiming to target these diseases, polypharmacological agents modulating both monoaminergic pathways and neuroinflammatory were addressed. A library of analogues of the natural product hispidol was prepared and evaluated for inhibition of monoamine oxidases (MAOs) isoforms. Several molecules emerged as selective potential MAO B inhibitors. The most promising compounds were further evaluated in vitro for their impact on microglia viability, induced production of proinflammatory mediators and MAO-B inhibition mechanism. Amongst tested compounds, 1p was a safe potent competitive reversible MAO-B inhibitor and inhibitor of microglial production of neuroinflammatory mediators; NO and PGE2. In-silico study provided insights into molecular basis of the observed selective MAO B inhibition. This study presents compound 1p as a promising lead compound for management of neurodegenerative disease. Graphical Abstract
Comparison of symptomatic vertebrobasilar plaques between patients with and without Diabetes Mellitus using computed tomographic angiography and vessel wall magnetic resonance imaging

Objectives Diabetes mellitus is significantly associated with posterior circulation ischemic stroke. We aimed to compare the characteristics of vertebrobasilar plaques in symptomatic patients with and without diabetes using high-resolution vessel wall magnetic resonance imaging and computed tomographic angiography. Methods From April 2017 to May 2021, cases from patients with transient ischemic attack or stroke in the posterior circulation territory who underwent high-resolution vessel wall magnetic resonance imaging and computed tomographic angiography were reviewed. Characteristics of culprit vertebrobasilar plaques were compared between patients with and without diabetes. Multivariate regression analysis was performed to assess the correlation between culprit plaque characteristics and diabetes. Results A total of 148 patients were included and 75 patients were diagnosed with diabetes mellitus. Patients with diabetes had more intraplaque hemorrhage, calcification, spotty calcification presence, and higher calcification volume (all p < 0.05) compared with those without diabetes. Multivariate analysis demonstrated differences in the presence of intraplaque hemorrhage (p = 0.045) and number of spotty calcifications (p = 0.047) were statistically significant after adjusting for baseline characteristics. Conclusions Symptomatic patients with diabetes have a higher incidence of intraplaque hemorrhage and larger calcification burden than those without diabetes, indicating the association of diabetes with more advanced plaque features in the posterior circulation.