Miracle-dz/UniFAR-FTUs huggingface dataset:
A Longitudinal and Gender Invariance Analysis of the Strengths and Difficulties Questionnaire Across Ages 3, 5, 7, 11, 14, and 17 in a Large U.K.-Representative Sample

Developmental invariance is important for making valid inferences about child development from longitudinal data; however, it is rarely tested. We evaluated developmental and gender invariance for one of the most widely used measures of child mental health: the parent-reported Strengths and Difficulties Questionnaire (SDQ). Using data from the large U.K. population-representative Millennium Cohort Study (N = 10,207; with data at ages 3, 5, 7, 11, 14, and 17 years), we tested configural, metric, scalar, and residual invariance in emotional problems, conduct problems, hyperactivity/inattention, prosociality, and peer problems. We found that the SDQ showed poor fit at age 3 in both males and females and at age 17 in males; however, it fit reasonably well and its scores were measurement invariant up to the residual level across gender at ages 5, 7, 11, and 14 years. Scores were also longitudinally measurement invariant across this age range up to the partial residual level. Results suggest that the parent-reported SDQ can be used to estimate developmental trajectories of emotional problems, conduct problems, hyperactivity/inattention, prosociality, and peer problems and their gender differences across the age range 5 to 14 years using a latent model. Developmental differences outside of this range may; however, partly reflect measurement differences.
Rapid Determination of Metronidazole and 2-Hydroxymetronidazole in Murine Blood Plasma.

Metronidazole is a drug used to treat bacterial and protozoan infections. Nowadays, it is one of the most frequently prescribed drugs worldwide. The main aim of this paper is to present a rapid, reliable and simple high-performance liquid chromatography (HPLC) method to determine metronidazole along with its primary metabolite, 2-hydroxymetronidazole, in plasma or serum using paracetamol as an internal standard. A total of 100% methanol was used to denature plasma proteins. After centrifugation, the supernatant was evaporated under nitrogen flow. The samples were dissolved in the mobile phase and injected into a Li-Chrospher RP-18 column. A total of 10 mmol/L NaH2PO4: acetonitrile (90:10, v/v) solution with a flow rate of 1 mL/min was used as the mobile phase. Metronidazole and 2-hydroxymetronidazole were detected at two different wavelengths at 320 nm and 311 nm, respectively. The method is characterized by high precision (relative standard deviation % < 6). The method was used for the determination of metronidazole and 2-hydroxymetronidazole in murine blood using small amounts of plasma (≤100 μL).
Acellular Dermal Matrix–Associated Complications in Implant-Based Breast Reconstruction: A Multicenter, Prospective, Randomized Controlled Clinical Trial Comparing Two Human Tissues

Background: Implant-based breast reconstruction accounts for the vast majority of breast reconstruction procedures and is commonly performed with human acellular dermal matrix. There is no consensus as to the optimal human acellular dermal matrix preparation, and high-quality evidence concerning comparative effectiveness is lacking. This study is the first prospective, multicenter, randomized controlled clinical trial to compare human acellular dermal matrix–related complications of the two most commonly used human acellular dermal matrices in implant-based breast reconstruction. The authors hypothesize that there will be no difference in infection, seroma, and reconstructive failure between FlexHD Pliable and AlloDerm RTU. Methods: The authors conducted a Level 1 prospective, randomized, controlled, multicenter clinical trial to assess complications associated with the use of two human acellular dermal matrices in immediate postmastectomy implant-based breast reconstruction across seven clinical sites. Group A patients received FlexHD Pliable (113 patients with 187 breast reconstructions), and group B patients received AlloDerm RTU (117 patients with 197 breast reconstructions). Results: There was no significant difference with respect to patient demographics, indications, comorbidities, and reconstruction approach between groups. Mean follow-up time was 10.7 ± 3.2 months. There was no statistical difference in the overall matrix-related complications between groups A and B (4.3 percent versus 7.1 percent, p = 0.233). Obesity (OR, 1.14; 95 percent CI, 1.05 to 1.24; p = 0.001) and prepectoral placement of matrix (OR, 4.53; 95 percent CI, 1.82 to 11.3; p = 0.001) were independently associated with greater risks of overall matrix-related complications. Conclusion: This work supports the use of human acellular dermal matrices in implant-based breast reconstruction and demonstrates no significant difference in matrix-related complication rates between FlexHD Pliable and AlloDerm RTU. Clinical Question/Level of Evidence: Therapeutic, I.
TRAIL induces proliferation in rodent pancreatic beta cells via AKT activation.

Strategies to increase functional pancreatic beta cell mass is of great interest in diabetes-related research. TNF-related apoptosis-inducing ligand (TRAIL) is well-known to promote proliferation and survival in various cell types, including vascular smooth muscle and endothelial cells. Correlation between the protective nature of TRAIL on these cells and its proliferative effect is noteworthy. TRAIL's seemingly protective/therapeutic effect in diabetes prompted us to question whether it may act as an inducer of proliferation in pancreatic beta cells. We used rat primary islet cells and MIN6 mouse beta cell line to investigate TRAIL-induced proliferation. Cell viability and/or death was analysed by MTT, WST-1, and annexin-V/PI assays, while proliferation rates and pathways were assessed via immunocytochemical and Western blot analyses. Receptor neutralization antibodies identified the mediator receptors. Recombinant soluble TRAIL (sTRAIL) treatment led to 1.6-fold increased proliferation in insulin-positive cells in dispersed rat islets compared to the untreated group, while adenovirus-mediated overexpression of TRAIL increased the number of proliferating beta cells up to more than 6-fold. sTRAIL or adenoviral vector-mediated TRAIL overexpression induced proliferation in MIN6 cells also. TRAIL's proliferative effect was mediated via AKT activation, which was suppressed upon specific inhibition. Neutralization of each TRAIL receptor reversed the proliferative effect to some degree, with the highest level of inhibition in death receptor 5 (DR5) blockage in MIN6 cells, and in decoy receptor 1 (DcR1) blockage in primary rat beta cells. Thus, TRAIL induces proliferation in rodent pancreatic beta cells through activation of the AKT pathway.
Inflammation‐driven brain and gut barrier dysfunction in stress and mood disorders

Regulation of emotions is generally associated exclusively with the brain. However, there is evidence that peripheral systems are also involved in mood, stress vulnerability vs. resilience, and emotion‐related memory encoding. Prevalence of stress and mood disorders such as major depression, bipolar disorder, and post‐traumatic stress disorder is increasing in our modern societies. Unfortunately, 30%–50% of individuals respond poorly to currently available treatments highlighting the need to further investigate emotion‐related biology to gain mechanistic insights that could lead to innovative therapies. Here, we provide an overview of inflammation‐related mechanisms involved in mood regulation and stress responses discovered using animal models. If clinical studies are available, we discuss translational value of these findings including limitations. Neuroimmune mechanisms of depression and maladaptive stress responses have been receiving increasing attention, and thus, the first part is centered on inflammation and dysregulation of brain and circulating cytokines in stress and mood disorders. Next, recent studies supporting a role for inflammation‐driven leakiness of the blood–brain and gut barriers in emotion regulation and mood are highlighted. Stress‐induced exacerbated inflammation fragilizes these barriers which become hyperpermeable through loss of integrity and altered biology. At the gut level, this could be associated with dysbiosis, an imbalance in microbial communities, and alteration of the gut–brain axis which is central to production of mood‐related neurotransmitter serotonin. Novel therapeutic approaches such as anti‐inflammatory drugs, the fast‐acting antidepressant ketamine, and probiotics could directly act on the mechanisms described here improving mood disorder‐associated symptomatology. Discovery of biomarkers has been a challenging quest in psychiatry, and we end by listing promising targets worth further investigation.
Highly diverse and highly successful: invasive Australian acacias have not experienced genetic bottlenecks globally.

BACKGROUND AND AIMS Invasive species may undergo rapid evolution despite very limited standing genetic diversity. This so-called genetic paradox of biological invasions assumes that an invasive species has experienced (and survived) a genetic bottleneck and then underwent local adaptation in the new range. In this study, we test how often Australian acacias (genus Acacia), one of the world's worst invasive tree groups, have experienced genetic bottlenecks and inbreeding. METHODS We collated genetic data from 51 different genetic studies on Acacia species to compare genetic diversity between native and invasive populations. These studies analysed 37 different Acacia species, with genetic data from the invasive ranges of 11 species, and data from the native range for 36 species (14 of these 36 species are known to be invasive somewhere in the world, and the other 22 are not known to be invasive). KEY RESULTS Levels of genetic diversity are similar in native and invasive populations, and there is little evidence of invasive acacia populations being extensively inbred. Levels of genetic diversity in native range populations also did not differ significantly between species that have and that do not have invasive populations. CONCLUSION We attribute our findings to the impressive movement, introduction effort, and human usage of Australian acacias around the world.
Increased Accumulation of α‐Synuclein in Inflamed Appendices of Parkinson's Disease Patients

The accumulation of α‐synuclein (α‐Syn) aggregates that leads to the onset of Parkinson's disease (PD) has been postulated to begin in the gastrointestinal tract. The normal human appendix contains pathogenic forms of α‐Syn, and appendectomy has been reported to affect the incidence of PD.
Marijuana Legalization and Household Spending on Food and Alcohol

Utilizing the Consumer Expenditure Interview Survey from 2005 to 2019, I study spending on food and alcohol following recreational marijuana law (RML). Exploiting differences in the timing of the passage of RMLs and employing two-way fixed-effects methods, I find that households located in states adopting these laws increase their quarterly spending on food, which is driven mainly by spending on food consumed away from home. Legalization of recreational marijuana also leads to increased quarterly spending on alcohol. These findings suggest a complementarity between food, alcohol, and marijuana.
Climate change and its effect on the vulnerability to zoonotic cutaneous leishmaniasis in Iran.

Zoonotic cutaneous leishmaniasis (ZCL) is an important vector-borne disease with an incidence of 15.8 cases per 100,000 people in Iran in 2019. Despite all efforts to control the disease, ZCL has expanded into new areas during the last decades. The aim of this study was to predict the best ecological niches for both vectors and reservoirs of ZCL under climate change scenarios in Iran. Several online scientific databases were searched. In this study, various scientific sources (Google Scholar, PubMed, SID, Ovid Medline, Web of Science, Irandoc, Magiran) were searched. The inclusion criteria for this study included all records with spatial information about vectors and reservoirs of ZCL which were published between 1980 and 2019. The bioclimatic data was downloaded from online databases. MaxEnt model was used to predict the ecological niches for each species under two climate change scenarios in two periods: the 2030s and 2050s. The results obtained from the model were analyzed in ArcMap to find the vulnerability of different provinces for the establishment of ZCL foci. The area under the curve (AUC) for all models was >0.8, which suggests the models are able to make an accurate prediction. The distribution of all studied species in different climatic conditions showed changes. The variables affecting each of the studied species are introduced in the article. The predicted maps show that by 2050 there will be more suitable areas for the co-occurrence of vector and reservoir(s) of ZCL in Iran compared to the current climate condition and RCP2.6 scenario. An area in the northwest of Iran is predicted to have suitable environmental conditions for both vectors and reservoirs of ZCL, although the disease has not yet been reported in this area. These areas should be considered for field studies to confirm these results and to prevent the establishment of new ZCL foci in Iran.
The First Immunocompetent Mouse Model of Strictly Human Pathogen, Borrelia recurrentis

The spirochetal bacterium Borrelia recurrentis causes louse-borne relapsing fever (LBRF). Borrelia recurrentis is unique because, as opposed to other Borrelia spirochetes, this strictly human pathogen is transmitted by lice. Despite the high mortality and historically proven epidemic potential and current outbreaks in African countries and Western Europe, research on LBRF has been obstructed by the lack of suitable animal models. ABSTRACT The spirochetal bacterium Borrelia recurrentis causes louse-borne relapsing fever (LBRF). B. recurrentis is unique because, as opposed to other Borrelia spirochetes, this strictly human pathogen is transmitted by lice. Despite the high mortality and historically proven epidemic potential and current outbreaks in African countries and Western Europe, research on LBRF has been obstructed by the lack of suitable animal models. The previously used grivet monkey model is associated with ethical concerns, among other issues. An existing immunodeficient mouse model does not limit bacteremia due to its impaired immune system. In this study, we used genetically diverse Collaborative Cross (CC) lines to develop the first LBRF immunocompetent mouse model. Out of 12 CC lines tested, CC046 mice consistently developed B. recurrentis-induced spirochetemia during the first 3 days postchallenge as concordantly detected by dark-field microscopy, culture, and quantitative PCR. However, spirochetemia was not detected from day 4 through day 10 postchallenge. The high-level spirochetemia (>107 cells/ml of blood) observed in CC046 mice was similar to that recorded in LBRF patients as well as immunocompetent mouse strains experimentally infected by tick-borne relapsing fever (RF) spirochetes, Borrelia hermsii and Borrelia persica. In contrast to the Old World and New World RF spirochetes, which develop multiple relapses (n = 3 to 9), B. recurrentis produced only single culture-detectable spirochetemia in CC046 mice. The lack of relapses may not be surprising, as LBRF patients and the grivet monkey model usually develop no or only 1 to 2 spirochetemic relapses. The novel model will now allow scientists to study B. recurrentis in the context of intact immunity.
Anticoagulation and In-Hospital Mortality From Coronavirus Disease 2019: A Systematic Review and Meta-Analysis

Hypercoagulability in coronavirus disease 2019 (COVID-19) may aggravate disease severity during hospitalization but the reported survival benefits from anticoagulation (AC) vary among studies. We performed a literature research to estimate pooled odds ratios (ORs) of in-hospital mortality and major bleeding comparing among intermediate-to-therapeutic dose AC, prophylactic dose AC, and no AC. Until October 22, 2020, PubMed, EMBASE, and Cochrane Library Database were searched for studies reporting AC utilization and mortality in COVID-19. Studies with suspected risk of bias were excluded before the synthesis of pooled ORs with 95% confidence intervals (CIs) using random-effects models. Of 37 identified studies (N = 19,510), 17 (N = 17,833) were aggregated in the meta-analysis. The overall mortality rate was 23.1% (95% CI 18.7-28.2). The pooled odds of mortality comparing anticoagulated to non-anticoagulated patients were similar, but lower in prophylactic dose AC group (OR 0.83; 95% CI 0.73-0.95). Notably, intermediate-to-therapeutic dose AC increased mortality (OR 1.60; 95% CI 1.11-2.31) and major bleeding compared to prophylactic dose AC (OR 3.33; 95% CI 2.34-4.72). Our findings support the optimal efficacy and safety profiles of prophylactic dose AC in hospitalized COVID-19 patients.
Validation of a smartphone application and wearable sensor for measurements of wrist motions

We developed a smartphone application to measure wrist motion using the mobile device’s built-in motion sensors or connecting it via Bluetooth to a wearable sensor. Measurement of wrist motion with this method was assessed in 33 participants on two occasions and compared with those obtained with a standard goniometer. The test–retest reproducibility in healthy individuals ranged from good to excellent (intraclass correlation (ICC) 0.76–0.95) for all motions, both with and without the wearable sensor. These results improved to excellent (ICC 0.90–0.96) on the second test day, suggesting a learning effect. The day-to-day reproducibility was overall better with the wearable sensor (mean ICC 0.87) compared with the application without using sensor or goniometer (mean ICC 0.82 and 0.60, respectively). This study suggests that smartphone-based measurements of wrist range of motion are feasible and highly accurate, making it a powerful tool for outcome studies after wrist surgery.
Myeloid‐resident neuropilin‐1 promotes choroidal neovascularization while mitigating inflammation

Age‐related macular degeneration (AMD) in its various forms is a leading cause of blindness in industrialized countries. Here, we provide evidence that ligands for neuropilin‐1 (NRP1), such as Semaphorin 3A and VEGF‐A, are elevated in the vitreous of patients with AMD at times of active choroidal neovascularization (CNV). We further demonstrate that NRP1‐expressing myeloid cells promote and maintain CNV. Expression of NRP1 on cells of myeloid lineage is critical for mitigating production of inflammatory factors such as IL6 and IL1β. Therapeutically trapping ligands of NRP1 with an NRP1‐derived trap reduces CNV. Collectively, our findings identify a role for NRP1‐expressing myeloid cells in promoting pathological angiogenesis during CNV and introduce a therapeutic approach to counter neovascular AMD.
The Cocaine and Oxycodone Biobanks, Two Repositories from Genetically Diverse and Behaviorally Characterized Rats for the Study of Addiction

Visual Abstract The rat oxycodone and cocaine biobanks contain samples that vary by genotypes (by using genetically diverse genotyped HS rats), phenotypes (by measuring addiction-like behaviors in an advanced SA model), timepoints (samples are collected longitudinally before, during, and after SA, and terminally at three different timepoints in the addiction cycle: intoxication, withdrawal, and abstinence or without exposure to drugs through age-matched naive rats), samples collected (organs, cells, biofluids, feces), preservation (paraformaldehyde-fixed, snap-frozen, or cryopreserved) and application (proteomics, transcriptomics, microbiomics, metabolomics, epigenetics, anatomy, circuitry analysis, biomarker discovery, etc. Substance use disorders (SUDs) are pervasive in our society and have substantial personal and socioeconomical costs. A critical hurdle in identifying biomarkers and novel targets for medication development is the lack of resources for obtaining biological samples with a detailed behavioral characterization of SUD. Moreover, it is nearly impossible to find longitudinal samples. As part of two ongoing large-scale behavioral genetic studies in heterogeneous stock (HS) rats, we have created two preclinical biobanks using well-validated long access (LgA) models of intravenous cocaine and oxycodone self-administration (SA) and comprehensive characterization of addiction-related behaviors. The genetic diversity in HS rats mimics diversity in the human population and includes individuals that are vulnerable or resilient to compulsive-like responding for cocaine or oxycodone. Longitudinal samples are collected throughout the experiment, before exposure to the drug, during intoxication, acute withdrawal, and protracted abstinence, and include naive, age-matched controls. Samples include, but are not limited to, blood plasma, feces and urine, whole brains, brain slices and punches, kidney, liver, spleen, ovary, testis, and adrenal glands. Three preservation methods (fixed in formaldehyde, snap-frozen, or cryopreserved) are used to facilitate diverse downstream applications such as proteomics, metabolomics, transcriptomics, epigenomics, microbiomics, neuroanatomy, biomarker discovery, and other cellular and molecular approaches. To date, >20,000 samples have been collected from over 1000 unique animals and made available free of charge to non-profit institutions through https://www.cocainebiobank. org/ and https://www.oxycodonebiobank. org/.
Association of Infarct Volume Before Hemicraniectomy and Outcome After Malignant Infarction

Objective To determine the impact of infarct volume before hemicraniectomy in malignant middle cerebral artery infarction (MMI) as an independent predictor for patient selection and outcome prediction, we retrospectively analyzed data of 140 patients from a prospective multicenter study. Methods Patients from the Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery (DESTINY) Registry who underwent hemicraniectomy after ischemic infarction of >50% of the middle cerebral artery territory were included. Functional outcome according to the modified Rankin Scale (mRS) was assessed at 12 months. Unfavorable outcome was defined as mRS score of 4 to 6. Infarct size was quantified semiautomatically from CT or MRI before hemicraniectomy. Subgroup analyses in patients fulfilling inclusion criteria of randomized trials in younger patients (age ≤60 years) were predefined. Results Among 140 patients with complete datasets (34% female, mean [SD] age 54 [11] years), 105 (75%) had an unfavorable outcome (mRS score >3). Mean (SD) infarct volume was 238 (63) mL. Multivariable logistic regression identified age (odds ratio [OR] 1.08 per 1-year increase, 95% confidence interval [CI] 1.02–1.13, p = 0.004), infarct size (OR 1.27 per 10-mL increase, 95% CI 1.12–1.44, p < 0.001), and NIH Stroke Scale score (OR 1.10, 95% CI 1.01–1.20, p = 0.030) before hemicraniectomy as independent predictors of unfavorable outcome. Findings were reproduced in patients fulfilling inclusion criteria of randomized trials in younger patients. Infarct volume thresholds for prediction of unfavorable outcome with high specificity (94% in overall cohort and 92% in younger patients) were >258 mL before hemicraniectomy. Conclusion Outcome in MMI depends strongly on age and infarct size before hemicraniectomy. Standardized volumetry may be helpful in the process of decision-making concerning hemicraniectomy.