Miracle-dz/UniFAR-FTUs huggingface dataset:
Ambient PM2.5 organic and elemental carbon in New York City: Changing source contributions during a decade of large emission reductions

ABSTRACT Fine particle (PM2.5) exposure is a public health issue affecting millions of people worldwide. In New York State, significant emission reductions occurred during the past decades due to fuel switching, increased renewable energy, and transformations in buildings and transportation. Between 2002 and 2018, anthropogenic emissions of CO, NOx, SO2, VOCs, and primary PM2.5 declined by 58%, 61%, 89%, 47%, and 29%, respectively, in New York and three adjoining states. Ambient PM2.5 mass concentrations decreased but contributions of source types to changes in PM2.5 elemental carbon (EC) and organic carbon (OC) are incompletely understood. Receptor modeling was used to estimate changing source contributions to EC and OC in New York City (NYC) between 2007 and 2019. Source identification was facilitated by incorporating measurements of CO, NO, NO2, O3, SO2, and speciated hydrocarbons (1,3-butadiene, n-butane, isobutane, n-pentane, isopentane, isoprene, benzene, toluene, xylenes, acetaldehyde, and formaldehyde). Hydrocarbon species identified mobile-source emissions, evaporative emissions, biogenics, and photochemical secondary organic aerosol. At three study locations, predicted reductions of TC (OC + EC) summed over all source types were 1.3 ± 0.2 μg m−3, compared with a measured TC reduction of 1.5 ± 0.2 μg m−3. Declining sulfate concentrations and cleaner mobile sources together reduced the predicted average TC by a combined 1 μg m−3. Smaller changes occurred in other source contributions, e.g., 0.15 ± 0.01 μg m−3 reduction likely in response to NYC regulations related to heating fuel oil. Biomass burning PM2.5 increased between 2007 and 2011, then declined between 2015 and 2019. Reductions contrast with a non-significant increase of 0.05 μg m−3 in photochemical TC. Further opportunities to decrease PM2.5 concentrations include wood burning and photochemical-related OC. Continued temporal analysis and source apportionment will be needed to track changes in air quality and source contributions as jurisdictions expand renewable energy and energy efficiency goals. Implications: Large emission reductions that occurred in the eastern U.S. between 2002 and 2019 lowered average fine particle concentrations in New York City by a factor of two. Secondary organic aerosol concentrations declined as sulfate decreased but increased non-significantly with rising ozone. Cleaner mobile-source emissions lowered elemental and organic carbon concentrations. Opportunities for further reductions of PM2.5 concentrations include biomass burning and photochemical secondary aerosol.
Curcumin and cancer biology: Focusing regulatory effects in different signalling pathways

Cancer is the second‐leading cause of death worldwide. Till date, many such effective treatments are available, for example chemotherapy, surgery, and radiation therapy, but there are severe associated side effects, such as increased infection risk, constipation, hair loss, anaemia, among others. Thus, the need for effective therapeutic strategies and screening methodology arises. Researchers around the world are increasingly trying to discover anticancer therapies with as few side effects as possible and many are now focusing on phytochemicals, like curcumin. Curcumin is a bright yellow substance isolated from the plant rhizomes of Curcuma longa L. To this molecule a high therapeutic benefit has been underlined, being able to alter the development of cancer by different mechanisms, such as regulating multiple microRNA expression, modifying a series of signalling pathways, that is, Akt, Bcl‐2, PTEN, p53, Notch, and Erbb. Another major pathway that curcumin targets is the matrix metalloproteinase (MMP) gene expression. In fact, MMPs are responsible for the degradation of the cell‐extracellular matrix, which can lead to the diseased condition and many different pathways contribute to its activity, such as JAK/STAT, NF‐κB, MAPK/ERK, COX‐2, ROS, TGF‐β, among others. In this review, we have attempted to describe the curcumin regulatory effect on different cell signalling pathways involved in the progression of different types of cancers.
Repeated exposure to JWH‐018 induces adaptive changes in the mesolimbic and mesocortical dopaminergic pathways, glial cells alterations, and behavioural correlates

Spice/K2 herbal mixtures, containing synthetic cannabinoids such as JWH‐018, have been marketed as marijuana surrogates since 2004. JWH‐018 has cannabinoid CB1 receptor‐dependent reinforcing properties and acutely increases dopaminergic transmission selectively in the NAc shell. Here, we tested the hypothesis that repeated administration of JWH‐018 (i) modulates behaviour, (ii) affects dopaminergic transmission and its responsiveness to motivational stimuli, and (iii) is associated with a neuroinflammatory phenotype.
Essential Role of Somatic Kv2 Channels in High-Frequency Firing in Cartwheel Cells of the Dorsal Cochlear Nucleus

Abstract Among all voltage-gated potassium (Kv) channels, Kv2 channels are the most widely expressed in the mammalian brain. However, studying Kv2 in neurons has been challenging because of a lack of high-selective blockers. Recently, a peptide toxin, guangxitoxin-1E (GxTX), has been identified as a specific inhibitor of Kv2, thus facilitating the study of Kv2 in neurons. The mammalian dorsal cochlear nucleus (DCN) integrates auditory and somatosensory information. In the DCN, cartwheel inhibitory interneurons receive excitatory synaptic inputs from parallel fibers conveying somatosensory information. The activation of parallel fibers drives action potentials in the cartwheel cells up to 130 Hz in vivo, and the excitation of cartwheel cells leads to the strong inhibition of principal cells. Therefore, cartwheel cells play crucial roles in monaural sound localization and cancelling detection of self-generated sounds. However, how Kv2 controls the high-frequency firing in cartwheel cells is unknown. In this study, we performed immunofluorescence labeling with anti-Kv2.1 and anti-Kv2.2 antibodies using fixed mouse brainstem slice preparations. The results revealed that Kv2.1 and Kv2.2 were largely present on the cartwheel cell body membrane but not on the axon initial segment (AIS) nor the proximal dendrite. Whole-cell patch-clamp recordings using mouse brainstem slice preparation and GxTX demonstrated that blockade of Kv2 induced failure of parallel fiber-induced action potentials when parallel fibers were stimulated at high frequencies (30–100 Hz). Thus, somatic Kv2 in cartwheel cells regulates the action potentials in a frequency-dependent manner and may play important roles in the DCN function.
DNA molecular combing-based replication fork directionality profiling

Abstract The replication strategy of metazoan genomes is still unclear, mainly because definitive maps of replication origins are missing. High-throughput methods are based on population average and thus may exclusively identify efficient initiation sites, whereas inefficient origins go undetected. Single-molecule analyses of specific loci can detect both common and rare initiation events along the targeted regions. However, these usually concentrate on positioning individual events, which only gives an overview of the replication dynamics. Here, we computed the replication fork directionality (RFD) profiles of two large genes in different transcriptional states in chicken DT40 cells, namely untranscribed and transcribed DMD and CCSER1 expressed at WT levels or overexpressed, by aggregating hundreds of oriented replication tracks detected on individual DNA fibres stretched by molecular combing. These profiles reconstituted RFD domains composed of zones of initiation flanking a zone of termination originally observed in mammalian genomes and were highly consistent with independent population-averaging profiles generated by Okazaki fragment sequencing. Importantly, we demonstrate that inefficient origins do not appear as detectable RFD shifts, explaining why dispersed initiation has remained invisible to population-based assays. Our method can both generate quantitative profiles and identify discrete events, thereby constituting a comprehensive approach to study metazoan genome replication.
Combination Therapy in Pulmonary Arterial Hypertension—Targeting the Nitric Oxide and Prostacyclin Pathways

Pulmonary arterial hypertension (PAH) is a chronic and progressive disorder characterized by vascular remodeling of the small pulmonary arteries, resulting in elevated pulmonary vascular resistance and ultimately, right ventricular failure. Expanded understanding of PAH pathophysiology as it pertains to the nitric oxide (NO), prostacyclin (prostaglandin I2) (PGI2) and endothelin-1 pathways has led to recent advancements in targeted drug development and substantial improvements in morbidity and mortality. There are currently several classes of drugs available to target these pathways including phosphodiesterase-5 inhibitors (PDE5i), soluble guanylate cyclase (sGC) stimulators, prostacyclin class agents and endothelin receptor antagonists (ERAs). Combination therapy in PAH, either upfront or sequentially, has become a widely adopted treatment strategy, allowing for simultaneous targeting of more than one of these signaling pathways implicated in disease progression. Much of the current treatment landscape has focused on initial combination therapy with ambrisentan and tadalafil, an ERA and PDE5I respectively, following results of the AMBITION study demonstrating combination to be superior to either agent alone as upfront therapy. Consequently, clinicians often consider combination therapy with other drugs and drug classes, as deemed clinically appropriate, for patients with PAH. An alternative regimen that targets the NO and PGI2 pathways has been adopted by some clinicians as an effective and sometimes preferred therapeutic combination for PAH. Although there is a paucity of prospective data, preclinical data and results from secondary data analysis of clinical studies targeting these pathways may provide novel insights into this alternative combination as a reasonable, and sometimes preferred, alternative approach to combination therapy in PAH. This review of preclinical and clinical data will discuss the current understanding of combination therapy that simultaneously targets the NO and PGI2 signaling pathways, highlighting the clinical advantages and theoretical biochemical interplay of these agents.
Cannabidiol inhibits the skeletal muscle Nav1.4 by blocking its pore and by altering membrane elasticity

Ghovanloo et al. combined in silico and in vitro approaches to determine the mechanism by which CBD inhibits the skeletal muscle Na+ channel Nav1.4. Their findings suggest that CBD acts directly, by binding inside the Nav1.4 pore, as well as indirectly, by modulating membrane elasticity.
Storying the Past and the Future

Abstract Research has linked disturbances in narrative identity with schizophrenia and other psychiatric disorders. One such disturbance is diminished agency and communion themes in past life stories. However, projecting oneself into the future is also central to identity and potentially impacts recovery. Hence, we examined themes of agency and communion in both past and future life stories and related themes to psychosocial functioning in 20 individuals with schizophrenia, 20 individuals with depressive disorder, and 19 nonpsychiatric controls. Participants were asked to describe up to 10 past and future chapters in their life stories and were assessed on psychosocial functioning and neurocognition. Chapters were coded for agency and communion themes. Both clinical groups displayed diminished agency and communion themes in past but not future life story chapters compared with the nonpsychiatric controls. Furthermore, agency themes in future chapters explained variance in psychosocial functioning after controlling for neurocognition. The results suggest that constructing a narrative identity to foster agency and communion in both past and future chapters may be an important part of recovering from schizophrenia and depression.
A multi-method examination of the link between obsessive-compulsive symptomatology and emotion-related impulsivity.

OBJECTIVES Obsessive-compulsive disorder (OCD) is a condition marked by recurrent and distressing thoughts, images, and urges accompanied by repetitive physical or mental rituals. An emerging line of work suggests that emotion may be an important consideration when looking at the role of impulsivity across the spectrum of psychopathology, including OCD. The current study examined the relationship between obsessive-compulsive symptomatology (OCS) and impulsive cognitive and behavioural reactions to emotion using a multi-study, multi-method approach. DESIGN Data were collected cross-sectionally online (Study 1) or via an in-person laboratory visit (Study 2). METHODS In Study 1, self-report measures of impulsivity and OCS were administered to a large, non-selected community sample (N = 386). Study 2 extended these findings with a young adult sample (N = 107) with clinically elevated OCS using self-report measures, clinical interview, and two behavioural symptom provocation tasks. RESULTS Emotion-related impulsivity, but not non-emotion-related impulsivity, was associated with greater severity of OCS across symptom domains and across all modes of assessment. Impulsive cognitive responses to emotion were associated with greater obsession severity, while impulsive behavioural reactions to emotion were associated with greater compulsions. Emotion-related impulsivity also acted synergistically with a belief in the importance and control of thoughts, such that this established risk factor for OCD was associated with greater OCS severity only when behavioural reactivity to emotion was also present. CONCLUSIONS Results highlight the importance of considering emotional context when studying impulsivity in OCD, and point to the potentially differential relationship between OCS and behavioural versus cognitive impulsive reactions to emotion. PRACTITIONER POINTS Emotion-related impulsivity (ERI) reflects a tendency to act impulsively in the context of strong emotions. ERI was associated with greater OCS across symptom domains and type of symptom assessment (self-report, interview, or symptom provocation). ERI also interacted with an established OCS risk factor, a belief in the importance and control of thoughts, to predict symptom severity, suggesting that it may be important to evaluate and address ERI alongside unhelpful beliefs in patients with OCS. Given the present study's cross-sectional nature, we cannot draw conclusions about the directionality of the ERI - OCS relationship, and while our study included individuals with clinically elevated OCS, results should be replicated in a fully clinical sample.
The cost of Medicare-funded medical and pharmaceutical services for mental disorders in children and adolescents in Australia

Objective To examine the health care costs associated with mental disorders and subthreshold mental disorders within a nationally representative sample of children and adolescents in Australia. Method Data were derived from the Young Minds Matter Survey (N = 6,310). Mental disorders were classified using the Diagnostic Interview Schedule for Children Version IV. Participant data were linked to administrative data on health care costs. Adjusted generalized linear regression models and two-part models were used to estimate mean differences in costs between those with a mental disorder or subthreshold disorder and those without. Results Costs associated with health care attendances and medications were higher for children and adolescents with mental disorders and subthreshold mental disorders compared to those without a mental disorder. The additional population health care costs due to mental disorders amounted to AUD$234 million annually in children and adolescents, of which approximately 16% was attributed to out-of-pocket costs. Findings showed that those with subthreshold mental disorders or comorbid mental disorders have substantial additional costs of Medicare-funded medical and pharmaceutical services. Conclusion and implication Mental disorders in children and adolescents are associated with significant health care costs. Further research is needed to ensure that this population is receiving effective and efficient care.
Impact of Previously Unrecognized HLA Mismatches Using Ultrahigh Resolution Typing in Unrelated Donor Hematopoietic Cell Transplantation

PURPOSE Ultrahigh resolution (UHR) HLA matching is reported to result in better outcomes following unrelated donor hematopoietic cell transplantation, improving survival and reducing post-transplant complications. However, most studies included relatively small numbers of patients. Here we report the findings from a large, multicenter validation study. METHODS UHR HLA typing was available on 5,140 conventionally 10 out of 10 HLA-matched patients with malignant disease transplanted between 2008 and 2017. RESULTS After UHR HLA typing, 82% of pairs remained 10 out of 10 UHR-matched; 12.3% of patients were 12 out of 12 UHR HLA-matched. Compared with 12 out of 12 UHR-matched patients, probabilities of grade 2-4 acute graft-versus-host disease (aGVHD) were significantly increased with UHR mismatches (overall P = .0019) and in those patients who were HLA-DPB1 T-cell epitope permissively mismatched or nonpermissively mismatched (overall P = .0011). In the T-cell–depleted subset, the degree of UHR HLA mismatch was only associated with increased transplant-related mortality (TRM) (overall P = .0068). In the T-cell–replete subset, UHR HLA matching was associated with a lower probability of aGVHD (overall P = .0020); 12 out of 12 UHR matching was associated with reduced TRM risk when compared with HLA-DPB1 T-cell epitope permissively mismatched patients, whereas nonpermissive mismatching resulted in a greater risk (overall P = .0003). CONCLUSION This study did not confirm that UHR 12 out of 12 HLA matching increases the probability of overall survival but does demonstrate that aGVHD risk, and in certain settings TRM, is lowest in UHR HLA-matched pairs and thus warrants consideration when multiple 10 out of 10 HLA-matched donors of equivalent age are available.
Faecalibacterium prausnitzii increases following fecal microbiota transplantation in recurrent Clostridioides difficile infection

Objective Fecal microbiota transplantation (FMT) is a highly effective treatment for Clostridioides difficile infection (CDI). However, the fecal transplant’s causal components translating into clearance of the CDI are yet to be identified. The commensal bacteria Faecalibacterium prausnitzii may be of great interest in this context, since it is one of the most common species of the healthy gut microbiota and produces metabolites with anti-inflammatory properties. Although there is mounting evidence that F. prausnitzii is an important regulator of intestinal homeostasis, data about its role in CDI and FMT are relatively scarce. Methods Stool samples from patients with recurrent CDI were collected to investigate the relative abundance of F. prausnitzii before and after FMT. Twenty-one patients provided fecal samples before the FMT procedure, at 2 weeks post-FMT, and at 2–4 months post-FMT. The relative abundance of F. prausnitzii was determined using quantitative polymerase chain reaction. Results The abundance of F. prausnitzii was elevated in samples (N = 9) from donors compared to pre-FMT samples (N = 15) from patients (adjusted P<0.001). No significant difference in the abundance of F. prausnitzii between responders (N = 11) and non-responders (N = 4) was found before FMT (P = 0.85). In patients with CDI, the abundance of F. prausnitzii significantly increased in the 2 weeks post-FMT samples (N = 14) compared to the pre-FMT samples (N = 15, adjusted P<0.001). The increase persisted 2–4 months post-FMT (N = 15) compared to pre-FMT samples (N = 15) (adjusted P<0.001). Conclusions FMT increases the relative abundance of F. prausnitzii in patients with recurrent CDI, and this microbial shift remains several months later. The baseline abundance of F. prausnitzii in donors or recipients was not associated with future treatment response, although a true predictive capacity cannot be excluded because of the limited sample size. Further studies are needed to discern whether F. prausnitzii plays an active role in the resolution of CDI.
Novel Predictors of COVID-19 Protective Behaviors Among US Adults: Cross-sectional Survey

Background A central component of the public health strategy to control the COVID-19 pandemic involves encouraging mask wearing and social distancing to protect individuals from acquiring and transmitting the virus. Objective This study aims to understand the psychological factors that drive adoption or rejection of these protective behaviors, which can inform public health interventions to control the pandemic. Methods We conducted an online survey of a representative sample of 1074 US adults and assessed three novel potential predictors of COVID-19 behaviors: trait reactance, COVID-19 conspiracy beliefs, and COVID-19 apocalypse beliefs. Key outcomes (dependent variables) included an index of COVID-19 protective behaviors, the number of trips taken from the home, and COVID-19 knowledge. Results In bivariate analyses, all three predictors were significantly correlated in the hypothesized direction with the three COVID-19 outcomes. Specifically, each predictor was negatively (P<.01) correlated with the COVID-19 protective behaviors index and COVID-19 knowledge score, and positively correlated with trips taken from home per week (more of which was considered higher risk). COVID-19 protective behaviors and COVID-19 knowledge were significantly lower in the top median compared to the bottom median for all three predictors. In general, these findings remained significant after adjusting for all novel predictors plus age, gender, income, education, race, political party, and religiosity. Self-identified Republicans (vs other political affiliations) reported the highest values for each of the novel predictors. Conclusions This study can inform the development of health communication interventions to encourage the adoption of COVID-19 protective behaviors. Interestingly, we found that higher scores of all three novel predictors were associated with lower COVID-19 knowledge, suggesting that lack of an accurate understanding of the virus may be driving some of these attitudes; although, it is also possible that these attributes may interfere with one’s willingness or ability to seek and absorb accurate health information. These individuals may be particularly immune to accepting new information and yielding their beliefs. Health communication professionals may apply lessons learned from countering similar beliefs around climate change and vaccine hesitancy. Messages designed for individuals prone to reactance may be more effective if they minimize controlling language and emphasize the individual’s independence in adopting these behavioral recommendations. Messaging for those who possess conspiracy beliefs should similarly not assume that providing evidence contrary to these beliefs will alone alter behavior. Other communication techniques such as rolling with resistance, a strategy used in motivational interviewing, may be helpful. Messaging for those with apocalyptic beliefs may require using religious leaders as the message source and using scripture that would support the adoption of COVID-19 protection behaviors.