Miracle-dz/UniFAR-FTUs huggingface dataset:
Deletion of TrkB in parvalbumin interneurons alters cortical neural dynamics

Signaling by neurotrophins such as the brain‐derived neurotrophic factor (BDNF) is known to modulate development of interneurons, but the circuit effects of this modulation remain unclear. Here, we examined the impact of deleting TrkB, a BDNF receptor, in parvalbumin‐expressing (PV) interneurons on the balance of excitation and inhibition (E‐I) in cortical circuits. In the mouse olfactory cortex, TrkB deletion impairs multiple aspects of PV neuronal function including synaptic excitation, intrinsic excitability, and the innervation pattern of principal neurons. Impaired PV cell function resulted in aberrant spiking patterns in principal neurons in response to stimulation of sensory inputs. Surprisingly, dampened PV neuronal function leads to a paradoxical decrease in overall excitability in cortical circuits. Our study demonstrates that, by modulating PV circuit plasticity and development, TrkB plays a critical role in shaping the evoked pattern of activity in a cortical network.
Parallel evaluation of cell-based phage display panning strategies: Optimized selection and depletion steps result in AML blast-binding consensus antibodies

Phage display technology (PD) is a powerful technique for the generation of tumor-targeting antibodies. However, there are a number of different selection methods established in different laboratories around the world. Cell-based PD panning methods using primary tumor cells are particularly heterogeneous between laboratories, which can lead to inconsistent results. Therefore, the present study evaluated different cell-based PD selection methods regarding their potential to generate acute myeloid leukemia (AML) blast-binding antibodies. In addition to this evaluation, the present study improved the PD procedure by optimizing selection as well as depletion strategies. To the best of our knowledge, the current study demonstrated for the first time that antigen diversity during the depletion step is of importance for the enrichment of tumor-targeting phage antibodies. It is demonstrated that medium levels of depletion antigen diversity led to the most promising antibody candidates. In addition, it was determined that purification of blast cells from patients with AML by immunomagnetic separation ameliorated the selection of AML-binding phages during panning. Furthermore, suggesting a common design-related mechanism using a ‘single-pot’ PD library, such as the well-known Tomlinson single-chain fragment variable (scFv) library, the present study identified specific binding consensus phage particles in independent panning procedures. By means of these optimized strategies, four promising AML blast-binding phage particles were isolated and soluble scFv-Fc (scFv cloned to a fragment crystallizable of an IgG2a mouse antibody) fusion proteins were produced. These scFv-Fc antibodies bound the surface of AML blasts and were successfully internalized into their cytoplasm, indicating that they are potential immunoconjugate candidates for AML immunotherapy.
Visual hallucinations in psychiatry – what aren’t we seeing?

Objective: To increase awareness of practising clinicians and researchers to the phenomenological distinctions between visual hallucinations and trauma-based, dissociative, visual re-experiencing phenomena seen in psychiatric disease. Conclusions: The experience of visual hallucinations is not exclusive to psychotic disorders in psychiatry. Different forms of experiences that resemble visual hallucinations may occur in patients with a trauma background and may potentially affect diagnosis. Given the paucity of literature around the subject, it is imperative that further research aims to characterise the distinction between visual hallucinations in psychosis and visual phenomena associated with trauma.
Analogy Generation in Science Experts and Novices

There is a critical inconsistency in the literature on analogical retrieval. On the one hand, a vast set of laboratory studies has found that people often fail to retrieve past experiences that share deep relational commonalities, even when they would be useful for reasoning about a current problem. On the other hand, historical studies and naturalistic research show clear evidence of remindings based on deep relational commonalities. Here, we examine a possible explanation for this inconsistency-namely, that remindings based on relational principles increase as a function of expertise. To test this claim, we devised a simple analogy-generation task that can be administered across a wide range of expertise. We presented common events as the bases from which to generate analogies. Although the events themselves were unrelated to geoscience, we found that when the event was explainable in terms of a causal principle that is prominent in geoscience, expert geoscientists were likely to spontaneously produce analogies from geoscience that relied on the same principle. Further, for these examples, prompts to produce causal analogies increased their frequency among nonscientists and scientists from another domain, but not among expert geoscientists (whose spontaneous causal retrieval levels were already high). In contrast, when the example was best explained by a principle outside of geoscience, all groups required prompting to produce substantial numbers of analogies based on causal principles. Overall, this pattern suggests that the spontaneous use of causal principles is characteristic of experts. We suggest that expert scientists adopt habitual patterns of encoding according to the key relational principles in their domain, and that this contributes to their propensity to spontaneously retrieve relational matches. We discuss implications for the nature of expertise and for science instruction and assessment.
Green Synthesis of Copper Nano-Drug and Its Dental Application upon Periodontal Disease-Causing Microorganisms

Dental pathogens lead to chronic diseases like periodontitis, which causes loss of teeth. Here, we examined the plausible antibacterial efficacy of copper nanoparticles (CuNPs) synthesized using Cupressus macrocarpa extract (CME) against periodontitis-causing bacteria. The antimicrobial properties of CME-CuNPs were then assessed against oral microbes (M. luteus. B. subtilis, P. aerioginosa) that cause periodontal disease and were identified using morphological/ biochemical analysis, and 16S-rRNA techniques. The CME-CuNPs were characterized, and accordingly, the peak found at 577 nm using UV–Vis spectrometer showed the formation of stable CME-CuNPs. Also, the results revealed the formation of spherical and oblong monodispersed CME-CuNPs with sizes ranged from 11.3 to 22.4 nm. The FTIR analysis suggested that the CME contains reducing agents that consequently had a role in Cu reduction and CME-CuNP formation. Furthermore, the CME-CuNPs exhibited potent antimicrobial efficacy against different isolates which was superior to the reported values in literature. The antibacterial efficacy of CME-CuNPs on oral bacteria was compared to the synergistic solution of clindamycin with CME-CuNPs. The solution exhibited a superior capacity to prevent bacterial growth. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and fractional inhibitory concentration (FIC) of CME-CuNPs with clindamycin recorded against the selected periodontal disease-causing microorganisms were observed between the range of 2.6–3.6 μg/ml, 4-5 μg/ml and 0.312-0.5, respectively. Finally, the synergistic antimicrobial efficacy exhibited by CME-CuNPs with clindamycin against the tested strains could be useful for the future development of more effective treatments to control dental diseases.
T OWARD U NDERSTANDING T RANSFORMER B ASED S ELF S UPERVISED M ODEL

Recently, transformer based large scale self supervised models such as BERT have drawn attention of researchers from different areas of NLP. As these models are deep neural networks with a large quantity of parameters, understanding their behavior in downstream tasks is challenging and attracts great research interest. A straightforward method of studying these neural network based models is to analyse their layer-wise representation by some algorithms like unsupervised clustering and compare the result with human’s manner in solving some downstream tasks like question answering [1]. Furthermore, as attention mechanism plays an important role in transformer, it is beneficial to analyse the behaviour of different attention heads in BERT [2]. Apart from the above intuitive methods, some new aspects have been proposed proposed recently to study the identifiability of attention weights[3].
Insight into the process of postpartum care utilisation and in-home support among vulnerable women in the Netherlands: an in-depth qualitative exploration

Objective To gain insight into the process of postpartum care utilisation and in-home support among vulnerable women. Design, method, participants and setting A qualitative interview study was conducted among 23 pregnant and postpartum vulnerable women in the Netherlands, following a grounded theory approach. Women were determined as vulnerable by their healthcare providers. Theoretical sampling of participants was applied and was alternated by data analysis to include information-rich cases until saturation was achieved. Results A conceptual framework of postpartum care utilisation was generated consisting of three phases: pregnancy, early postpartum period and late postpartum period. Within these phases, information provision, parenting self-efficacy and social network were identified as overarching themes. Perceived inadequate information on content of postpartum care posed a major barrier to forming realistic expectations during pregnancy and hindered its utilisation. Low self-efficacy facilitated postpartum care utilisation. All women experienced increased self-efficacy during and after postpartum care. Support from a social network influenced expectations regarding the added value of postpartum care during pregnancy, and lowered actual utilisation during the postpartum period. The costs of postpartum care and the role of the maternity care assistant acted as general barriers or facilitators influencing the three overarching themes and therefore postpartum care utilisation indirectly. Conclusions Our findings suggest that postpartum care utilisation among vulnerable women may be improved by considering the particular phase and relevant themes applying to individual women, and adapt care accordingly. We recommend to provide comprehensive, understandable information and to emphasise the gains of postpartum care in improving self-efficacy for vulnerable women. Moreover, involving a woman’s social network in postpartum care may add value to this care for this population.
Predictors of district nursing care utilisation for community-living people in the Netherlands: an exploratory study using claims data

Objective To explore predictors of district nursing care utilisation for community-living (older) people in the Netherlands using claims data. To cope with growing demands in district nursing care, knowledge about the current utilisation of district nursing care is important. Setting District nursing care as a part of primary care. Participants In this nationwide study, claims data were used from the Dutch risk adjustment system and national information system of health insurers. Samples were drawn of 5500 pairs of community-living people using district nursing care (cases) and people not using district nursing care (controls) for two groups: all ages and aged 75+ years (total N=22 000). Outcome measures The outcome was district nursing care utilisation and the 114 potential predictors included predisposing factors (eg, age), enabling factors (eg, socioeconomic status) and need factors (various healthcare costs). The random forest algorithm was used to predict district nursing care utilisation. The performance of the models and importance of predictors were calculated. Results For the population of people aged 75+ years, most important predictors were older age, and high costs for general practitioner consultations, aid devices, pharmaceutical care, ambulance transportation and occupational therapy. For the total population, older age, and high costs for pharmaceutical care and aid devices were the most important predictors. Conclusions People in need of district nursing care are older, visit the general practitioner more often, and use more and/or expensive medications and aid devices. Therefore, close collaboration between the district nurse, general practitioner and the community pharmacist is important. Additional analyses including data regarding health status are recommended. Further research is needed to provide an evidence base for district nursing care to optimise the care for those with high care needs, and guide practice and policymakers’ decision-making.
An evidence-based multidisciplinary approach focused at creating algorithms for targeted therapy of infection-related ventilator associated complications (IVACs) caused by Enterobacterales in critically ill adult patients

ABSTRACT Introduction Prompt implementation of appropriate targeted antibiotic therapy representsa valuable approach in improving clinical and ecological outcome in critically septic patients. Thismultidisciplinary opinion article aims to develop evidence-based algorithms for targeted antibiotictherapy of infection-related ventilator associated complications (IVACs) caused by Enterobacterales,which are among the most common pathogens associated with these conditions. Areas covered A multidisciplinary team of four experts had several rounds of assessment for developingalgorithms devoted to targeted antimicrobial therapy of IVACs caused by Enterobacterales.A literature search was performed on PubMed-MEDLINE (until March 2021) to provide evidence forsupporting therapeutic choices. Quality and strength of evidence was established according toa hierarchical scale of the study design. Six different algorithms with associated recommendations concerning therapeutic choice and dosing optimization were suggested according to the susceptibilitypattern of Enterobacterales: multi-susceptible, extended-spectrum beta-lactamase (ESBL)-producing,AmpC beta-lactamase-producing, Klebsiella pneumoniae carbapenemase (KPC)-producing, OXA-48-producing, and metallo-beta-lactamase (MBL)-producing Enterobacterales. Expert opinion The implementation of algorithms focused on prompt revision of antibiotic regimensguided by results of conventional and rapid diagnostic methodologies, appropriate place in therapy ofnovel beta-lactams, implementation of strategies for sparing the broadest-spectrum antibiotics, and PK/PD optimization of antibiotic dosing regimens is strongly suggested.
Victimization and Resilience: Experiences of Rural LGBTQ+ Youth Across Multiple Contexts

LGBTQ+ youth experience higher rates of interpersonal violence, such as peer-based bullying and identity-based harassment, than their counterparts. Experiences of victimization can occur across different social contexts including family, school, peers, and community. LGBTQ+ youth in rural communities may be at increased risk for identity-based victimization due in part to geographic isolation and an often conservative value system that may create a hostile environment to LGBTQ+ individuals. However, few studies have examined the experiences of rural LGBTQ+ youth from their perspectives, and how the rural context may affect their experiences with victimization and social support. This qualitative study explores the victimization experiences of rural LGBTQ+ youth, the supports available to them, and ways they show resilience. We conducted qualitative interviews with a sample of 11 young people ages 12-21, recruited in partnership with a local LGBTQ+ agency across a rural five county region in the Southeastern United States. Four themes emerged related to how rural youth navigate bullying, harassment, and victimization across different social contexts and the support that is available to them: (1) conflicting family messages, (2) navigating personal safety at school, (3) connecting through technology, and (4) confronting negative religious sentiment. A fifth theme captures the strengths of young people in the mid of victimization: (5) demonstrating individual and collective resilience. Although rural LGBTQ+ youth experience victimization in similar ways to urban and suburban youth, rural youth may have less access to social supports that buffer effects of victimization. This study highlights the strengths in rural LGBTQ+ young people as well as their commitment to supporting one another and seeing change in their communities. Findings illustrate a need for greater support for LGBTQ+ youth in rural areas while leveraging existing strength of the youth and their community for sustainable support and resources.
Tick exposure and risk of tick‐borne pathogens infection in hunters and hunting dogs: a citizen science approach

Abstract Citizen science may be described as a research involving communities and individuals, other than scientists. Following this approach, along with the evidence of a high prevalence of Rickettsia spp. in Dermacentor marginatus from wild boars in hunting areas of southern Italy, this study aimed to assess the occurrence of tick‐borne pathogens (TBPs) in ticks collected from hunters and their hunting dogs. From October 2020 to May 2021, ticks were collected from wild boar hunters (n = 347) and their dogs (n = 422) in regions of southern Italy (i.e., Apulia, Basilicata, Calabria, Campania and Sicily). All ticks were morphologically identified, classified according to gender, feeding status, host, geographic origin, and molecularly screened for zoonotic bacteria. Adult ticks (n = 411) were collected from hunters (i.e., n = 29; 8.4%; mean of 1.6 ticks for person) and dogs (i.e., n = 200; 47.4%; mean of 1.8 ticks for animal) and identified at species level as D. marginatus (n = 240, 58.4%), Rhipicephalus sanguineus sensu lato (n = 135, 32.8%), Rhipicephalus turanicus (n = 27, 6.6%) and Ixodes ricinus (n = 9, 2.2%). Overall, 45 ticks (i.e., 10.9%, 95% CI: 8.3‐14.3) tested positive for at least one tick‐borne agent, being Rickettsia slovaca the most frequent species (n = 37, 9.0%), followed by Rickettsia raoultii, Rickettsia aeschlimannii, Rickettsia monacensis, Coxiella burnetii, Borrelia lusitaniae and Candidatus Midichloria mitochondrii (n = 2, 0.5% each). Data herein presented demonstrate a relevant risk of exposure to TBPs for hunters and hunting dogs during the hunting activities. Therefore, the role of hunters to monitor the circulation of ticks in rural areas may be considered an effective example of the citizen science approach, supporting the cooperation toward private and public health stakeholders.
Association between subjective cognitive decline and falls in middle-aged adults

Abstract Falling experiences and the fear of falling in relation to subjective cognitive decline (SCD) was examined in middle-aged Koreans. A nationwide cross-sectional study was conducted using data from the 2019 Korea Community Health Survey. The final analysis included 92,323 individuals aged 40–64 years who had available data on SCD and falls. A multivariate regression model was applied to examine the independent effect of SCD on falls. Approximately 10.7% of participants had experienced a fall in the previous 12 months. Stepwise multivariate regression analysis showed that SCD was independently associated with a falling experience (adjusted odds ratio [95% confidence interval], 1.16 [1.53–1.70]); individuals with SCD were more likely to experience falling (13.9% vs. 9.14%, p < 0.001) and had more fear of falling (2.33% vs. 1.74%, p < 0.001). In conclusion, SCD is independently associated with falls in the middle-aged, which highlight the clinical need to investigate cognitive deficits among this population.
Non-alcoholic fatty liver disease and incident major adverse cardiovascular events: results from a nationwide histology cohort

Objective Some data suggest a positive association between non-alcoholic fatty liver disease (NAFLD) and incident major adverse cardiovascular events (MACEs). However, data are lacking from large cohorts with liver histology, which remains the gold standard for staging NAFLD severity. Design This population-based cohort included all Swedish adults with histologically confirmed NAFLD and without cardiovascular disease (CVD) at baseline (1966–2016, n=10 422). NAFLD was defined from prospectively recorded histopathology and categorised as simple steatosis, non-fibrotic steatohepatitis, non-cirrhotic fibrosis and cirrhosis. Patients with NAFLD were matched to ≤5 population controls without NAFLD or CVD, by age, sex, calendar year and county (n=46 517). Using Cox proportional hazards modelling, we calculated multivariable adjusted HRs (aHRs) and 95% CIs for MACE outcomes (ie, ischaemic heart disease (IHD), stroke, congestive heart failure (CHF) or cardiovascular (CV) mortality). Results Over a median of 13.6 years, incident MACE was confirmed in 2850 patients with NAFLD and 10 648 controls. Patients with NAFLD had higher incidence of MACE than controls (24.3 vs 16.0/1000 person-years (PY); difference=8.3/1000 PY; aHR 1.63, 95% CI 1.56 to 1.70), including higher rates of IHD (difference=4.2/1000 PY; aHR 1.64, 95% CI 1.54 to 1.75), CHF (difference=3.3/1000 PY; aHR 1.75, 95% CI 1.63 to 1.87), stroke (difference=2.4/1000 PY; aHR 1.58, 95% CI 1.46 to 1.71) and CV mortality (difference=1.2/1000 PY; aHR 1.37, 95% CI 1.27 to 1.48). Rates of incident MACE increased progressively with worsening NAFLD severity (ptrend=0.02), with the highest incidence observed with cirrhosis (difference vs controls=27.2/1000 PY; aHR 2.15, 95% CI 1.77 to 2.61). Conclusion Compared with matched population controls, patients with biopsy-proven NAFLD had significantly higher incidence of MACE, including IHD, stroke, CHF and CV mortality. Excess risk was evident across all stages of NAFLD and increased with worsening disease severity.
Subgingival Microbial Profiles of Young Chinese Adults with Stage I/II Periodontitis, Gingivitis and Periodontal Health Status.

OBJECTIVE To analyse the subgingival microbiota of Stage I/II periodontitis, gingivitis with different degrees of severity, and periodontal health in subjects in a Chinese young adult population. METHODS Subgingival plaque samples were collected from 15 Stage I/II periodontitis patients, 38 gingivitis patients and 15 periodontally healthy individuals, all aged from 18 to 21 years. Gingivitis patients were divided into two subgroups according to the Bleeding Index (BI) of their sampled teeth: gingivitis with above median BI (G-HBI) and below median BI (G-LBI). The subgingival plaque samples were collected from teeth 16, 26, 36, 46, 11 and 31 according to FDI notation. The V3-V4 region of the 16S rRNA gene of all the samples was sequenced and analysed. RESULTS The Stage I/II periodontitis, gingivitis and periodontal health groups showed distinct subgingival microbiota profiles. When the gingivitis patients were stratified into two subgroups, the community structure of G-HBI showed no significant difference from early-stage periodontitis, but differed from G-LBI and the healthy group. Most periodontitis-related taxa were most abundant in Stage I/II periodontitis, followed by G-HBI, G-LBI and the periodontally healthy group. Porphyromonas gingivalis, Filifactor alocis, Tannerella forsythia, Saccharibacteria TM7 G-5 356, Lachnospiraceae G-8 500, Peptostreptococcaceae spp. and Syntrophomonadaceae VIIIG-1 435 were associated with Stage I/II periodontitis. Porphyromonas 275, Leptotrichia 417 and Saccharibacteria TM7 G-2 350 were associated with gingivitis. Porphyromonas gingivalis was significantly more abundant in G-HBI than in G-LBI. CONCLUSION Within the limitations of this preliminary study, gingivitis and early-stage periodontitis were associated with an increased degree of dysbiosis in the subgingival microbiota in a Chinese young adult population.