Miracle-dz/UniFAR-FTUs huggingface dataset:
The Indirect Effect of Peritraumatic Dissociation on the Relationship Between Childhood Maltreatment and Schizotypy

Schizotypy is a multidimensional personality construct that is understood as a vulnerability for schizophrenia, often manifesting as more subtle and attenuated symptoms, referred to as schizotypic psychopathology. It has many well-established environmental risk factors, including experiencing childhood maltreatment (CM), but the intermediary mechanisms that relate CM to schizotypic psychopathology are unclear. Prior studies have demonstrated that trait dissociation may indirectly affect the relationship between CM and schizotypic psychopathology. However, less is known about the importance of peritraumatic dissociative experiences during CM and how it relates to schizotypic symptom manifestations in young adulthood. Therefore, the present study explored the independent contributions of peritraumatic and trait dissociation in the relationship between CM and schizotypy. Participants (N = 346) were undergraduate students who completed online self-report measures on CM, trait dissociation, peritraumatic dissociation experienced during CM, and schizotypic symptoms. The indirect effect of peritraumatic dissociation and trait dissociation on the relationship between CM and schizotypy was examined using mediational analyses. Correlational analyses revealed significant associations between self-reported CM, schizotypy, trait dissociation, and peritraumatic dissociation. In addition, mediational analyses indicated a significant indirect effect of peritraumatic dissociation (β = .06, 95% confidence interval (CI) [0.01, 0.12]), but not trait dissociation (β = .05, 95% CI [−0.02, 0.12]), on CM and schizotypy. These results highlight peritraumatic dissociation as an important mechanism driving the expression of schizotypic symptoms among individuals with a history of CM. Understanding how trauma sequelae lead to schizotypic psychopathology may be crucial in assessing and treating individuals with maltreatment histories or those on the psychosis spectrum.
C-reactive protein and uric acid roles in distinguishing ST-segment elevation myocardial infarction from non-ST-elevation acute coronary syndrome

ABSTRACT Acute coronary syndrome (ACS) is defined as a range of conditions which the blood flow to the heart was reduced or stopped. This disorder is correlated to a systemic inflammatory response and some biochemical factors. Therefore, the aim of this study was investigations of serum C-reactive protein (CRP) and uric acid levels in ST-segment elevation myocardial infarction (STEMI) and non-ST-elevation ACS (NSTE ACS), as common subtypes of ACS. Patients with ACS (n = 140) were assessed with coronary arteriography and divided into STEMI and NSTE ACS groups. The serum levels of hs-CRP and uric acid were investigated using a routine clinical chemistry analyzer. Patients with STEMI showed a significant increase in uric acid level compared to those with NSTE ACS (P < .0001). Other data indicated that hs-CRP level in patients with STEMI was significantly higher than individuals with NSTE ACS (P < .0001). Modeling analysis revealed that the increased levels of acid uric and hs-CRP in patients with STEMI were independent of the effects of age, gender, background diseases, and familial history (P < .001). The current study provides further evidence to indicate that hs-CRP and uric acid may be considered as biofactors for comparing STEMI from NSTE ACS and determining disease outcome.
Genesis , e ¡ ects and fatesof repeats in prokaryoticgenomes

DNA repeats are causes and consequences of genome plasticity. Repeats are created by intrachromosomal recombination or horizontal transfer. They are targeted by recombination processes leading to amplifications, deletions and rearrangements of genetic material. The identification and analysis of repeats in nearly 700 genomes of bacteria and archaea is facilitated by the existence of sequence data and adequate bioinformatic tools. These have revealed the immense diversity of repeats in genomes, from those created by selfish elements to the ones used for protection against selfish elements, from those arising from transient gene amplifications to the ones leading to stable duplications. Experimental works have shown that some repeats do not carry any adaptive value, while others allow functional diversification and increased expression. All repeats carry some potential to disorganize and destabilize genomes. Because recombination and selection for repeats vary between genomes, the number and types of repeats are also quite diverse and in line with ecological variables, such as host-dependent associations or population sizes, and with genetic variables, such as the recombination machinery. From an evolutionary point of view, repeats represent both opportunities and problems. We describe how repeats are created and how they can be found in genomes. We then focus on the functional and genomic consequences of repeats that dictate their fate.
Attentional M100 gain modulation localizes to auditory sensory cortex and is deficient in first‐episode psychosis

Selective attention is impaired in first‐episode psychosis (FEP). Selective attention effects can be detected during auditory tasks as increased sensory activity. We previously reported electroencephalography scalp‐measured N100 enhancement is reduced in FEP. Here, we localized magnetoencephalography (MEG) M100 source activity within the auditory cortex, making novel use of the Human Connectome Project multimodal parcellation (HCP‐MMP) to identify precise auditory cortical areas involved in attention modulation and its impairment in FEP. MEG was recorded from 27 FEP and 31 matched healthy controls (HC) while individuals either ignored frequent standard and rare oddball tones while watching a silent movie or attended tones by pressing a button to oddballs. Because M100 arises mainly in the auditory cortices, MEG activity during the M100 interval was projected to the auditory sensory cortices defined by the HCP‐MMP (A1, lateral belt, and parabelt parcels). FEP had less auditory sensory cortex M100 activity in both conditions. In addition, there was a significant interaction between group and attention. HC enhanced source activity with attention, but FEP did not. These results demonstrate deficits in both sensory processing and attentional modulation of the M100 in FEP. Novel use of the HCP‐MMP revealed the precise cortical areas underlying attention modulation of auditory sensory activity in healthy individuals and impairments in FEP. The sensory reduction and attention modulation impairment indicate local and systems‐level pathophysiology proximal to disease onset that may be critical for etiology. Further, M100 and N100 enhancement may serve as outcome variables for targeted intervention to improve attention in early psychosis.
Prevalence of oral and anal human papillomavirus infection in Czech predominantly HIV-positive men having sex with men - data from a previously unreported population

Background: HIV-positive men who have sex with men (MSM) are more likely to experience human papillomavirus (HPV) infection. The persistent HPV infection is the major factor in the development of anal and oropharyngeal neoplasms. Data on the prevalence of anal and oral HPV in MSM are almost absent from the countries of Central and Eastern Europe. We conducted a cross-sectional study focused on the prevalence of oral and anal HPV infections and the relationship between current anal and oral HPV intrapersonal infection in a Czech population of predominantly HIV-positive MSM. Methods: Oral gargle and anal swab samples from 205 predominantly HIV-positive MSM from the Czech Republic were analysed for HPV infection using PCR. Selected sociodemographic and clinical data were correlated with HPV detection using generalized linear models and multivariate analysis. Results: HPV infection was detected in 183 (96.8%) anal and 48 (23.6%) oral samples. The most common type of HR-HPV was HPV16 in both anal (25.4%) and oral (2.5%) samples. Multiple anal HPV infections and the presence of vaccine-targeted HR-HPV types were significantly correlated with abnormal anal cytology and HIV status. Conclusion: The prevalence of anal HPV infection in Czech predominantly HIV-positive MSM ranks among the highest reported, while oral HPV prevalence is consistent with MSM populations. Minimal overlap of oral and anal HPV types within a patient was observed.
A qualitative study of the impact of the COVID‐19 pandemic on women seeking pelvic organ prolapse surgery in Alberta, Canada

Abstract In addition to altering public infrastructure and social patterning, the COVID‐19 pandemic has delayed many pelvic organ prolapse (POP) surgeries. POP‐related stigma, symptomology and the experience of waiting for POP surgery can negatively impact women's quality of life and mental health. The experience of preoperative POP patients during the pandemic thus entails a new intersection of gendered, stigmatic and medical realities. Qualitative interviews were conducted with 26 preoperative POP patients as part of a larger qualitative study, 20 of whom spontaneously volunteered information about how the pandemic coloured their experience living with and awaiting surgery for POP. Interviews occurred between January and July 2021, which coincided with the second and third waves of the pandemic in Alberta, Canada, and before full immunisation was available for all Albertans. Pandemic‐related interview excerpts were thematically analysed, and four main findings emerged. (1) Though surgical delay meant living with unpleasant symptoms for longer than anticipated, some sought this out in order to protect vulnerable loved ones from possible hospital‐acquired infection, (2) shifting and unclear hospital policies and logistics resulted in intense preoperative stress, at times causing women to temporarily cease treatment, (3) decreased access to public restroom infrastructure caused women to reduce their outings and (4) the imperative to minimise social gatherings made it easier for women to engage in POP‐related, shame‐based self‐isolation without the notice of friends and family. As they can influence postoperative outcomes and treatment adherence, trends observed should be of interest to clinicians and policymakers alike.
Many ways, one microorganism: Several approaches to study Malassezia in interactions with model hosts

Malassezia, a lipophilic and lipid-dependent yeast, is a microorganism of current interest to mycobiologists because of its role as a commensal or pathogen in health conditions such as dermatological diseases, fungemia, and, as discovered recently, cancer and certain neurological disorders. Various novel approaches in the study of Malassezia have led to increased knowledge of the cellular and molecular mechanisms of this yeast. However, additional efforts are needed for more comprehensive understanding of the behavior of Malassezia in interactions with the host. This article reviews advances useful in the experimental field for Malassezia.
Exogenous signaling repairs defective T cell signaling inside the tumor microenvironment for better immunity

It is known that tumor-reactive T cells are initially activated in the draining lymph node, but it is not well known whether and how tumor-infiltrating lymphocytes (TILs) are reactivated in the tumor microenvironment (TME). We hypothesize that defective T cell receptor (TCR) signaling and cosignals in the TME limit T cell reactivation. To address this, we designed a mesenchymal stromal cell–based delivery of local membrane-bound anti-CD3 and/or cosignals to explore their contribution to reactivate T cells inside the TME. Combined anti-CD3 and CD40L rather than CD80 led to superior antitumor efficacy compared with either alone. Mechanistically, TCR activation of preexisting CD8+ T cells synergized with CD40L activation of DCs inside the TME for optimum tumor control. Exogenous TCR signals could better reactivate TILs that then exited to attack distal tumors. This study supplies further evidence that TCR signaling for T cell reactivation in the TME is defective but can be rescued by proper exogenous signals.
Acinetobacter baumannii–calcoaceticus Complex-associated Orbital Cellulitis: A Case Report and Literature Review

ABSTRACT Acinetobacter baumannii–calcoaceticus complex is emerging as one of the most common causes of hospital-acquired infection globally. We present a case of orbital cellulitis caused by the A. baumannii–calcoaceticus complex. A 73-year-old Chinese woman with a history of rheumatoid arthritis presented with subacute onset of right upper eyelid swelling for 1 week. Computer tomography revealed a post-septal soft tissue lesion located at the right superior orbit that was enhanced with contrast, compressing on the superior aspect of the globe. Anterior orbitotomy with incisional biopsy of the right superior orbital lesion was performed, and histopathological examination was consistent with nonspecific inflammatory mass. The microbiological culture of the specimen yielded A. calcoaceticus and A. baumannii complex, which was sensitive to ciprofloxacin, ampicillin, and gentamicin. The infection resolved after a 1-week course of intravenous augmentin. Ophthalmologists should be alert to the possibility of patients having A. baumannii and A. calcoaceticus in periorbital cellulitis.
Pulmonary embolism: an underdiagnosed and underreported entity in Brazil

Several registries in different countries have also shown an increase in PE hospitalizations in recent decades. (2) An American registry recorded a significant increase in hospitalizations due to PE after the introduction of computed tomographic pulmonary angiography (CTPA) for the diagnosis of this condition (62.1/100,000 inhab. vs. 112.3/100,000 inhab.; p < 0.0001) comparing the periods before and after 1998, when multi-detector computed tomography was introduced. (3) A Spanish registry also showed an increase in PE hospitalizations, from 20.44/100,000 inhab. in 2002 to 32.69/100,000 inhab. in 2011; p < 0.05. (4) Similar findings were observed in registries in Italy and Australia. (5,6)
Chromosome-level genome assembly and functional characterization of terpene synthases provide new insights into the volatile terpenoid biosynthesis of Wurfbainia villosa.

Wurfbainia villosa is a well-known medicinal and edible plant that is widely cultivated in the Lingnan region of China. Its dried fruits (called Fructus Amomi) are broadly used in traditional Chinese medicine for curing gastrointestinal diseases and are rich in volatile terpenoids. Here, we report a high-quality chromosome-level genome assembly of W. villosa with a total size of ~2.80 Gb, 42,588 protein-coding genes, and a very high percentage of repetitive sequences (87.23%). Genome analysis showed that W. villosa likely experienced a recent whole-genome duplication (WGD) event prior to the W. villosa-Zingiber officinale divergence (~11 MYA), and a recent burst of long terminal repeat (LTR) insertions afterward. The W. villosa genome enabled the identification of 17 genes involved in the terpenoid skeleton biosynthesis pathway and 66 terpene synthase (TPS) genes. We found that tandem duplication events have an important contribution to the expansion of WvTPSs, which likely drove the production of volatile terpenoids. In addition, functional characterization of 18 WvTPSs, focusing on the TPS-a and TPS-b subfamilies, showed that most of these WvTPSs are multi-product TPS and are predominantly expressed in seeds. This work provides insights into the genome evolution and the molecular basis of the volatile terpenoids diversity in W. villosa. The genome sequence also represents valuable resources for the functional gene research and molecular breeding of W. villosa.
CD200 ectodomain shedding into the tumor microenvironment leads to NK cell dysfunction and apoptosis

The basis of immune evasion, a hallmark of cancer, can differ even when cancers arise from one cell type such as in the human skin keratinocyte carcinomas: basal and squamous cell carcinoma. Here we showed that the basal cell carcinoma tumor–initiating cell surface protein CD200, through ectodomain shedding, was responsible for the near absence of NK cells within the basal cell carcinoma tumor microenvironment. In situ, CD200 underwent ectodomain shedding by metalloproteinases MMP3 and MMP11, which released biologically active soluble CD200 into the basal cell carcinoma microenvironment. CD200 bound its cognate receptor on NK cells to suppress MAPK pathway signaling that in turn blocked indirect (IFN-γ release) and direct cell killing. In addition, reduced ERK phosphorylation relinquished negative regulation of PPARγ-regulated gene transcription and led to membrane accumulation of the Fas/FADD death receptor and its ligand, FasL, which resulted in activation-induced apoptosis. Blocking CD200 inhibition of MAPK or PPARγ signaling restored NK cell survival and tumor cell killing, with relevance to many cancer types. Our results thus uncover a paradigm for CD200 as a potentially novel and targetable NK cell–specific immune checkpoint, which is responsible for NK cell–associated poor outcomes in many cancers.
Lyapunov stability, semistability, and asymptotic stability of matrix second-order systems

This paper provides a self-contained, unified and extended treatment of the stability of matrix second-order systems. The results we obtain encompass numerous results from prior literature in addition'to several new results. Specifically, in addition to obtaining necessary and sufficient conditions for Lyapunov and asymptotic stability, we consider the case of semistability. Semistability is of particular interest in the analysis of vibrating systems in that it represents the case of "damped rigid body modes", that is, systems that eventually come to rest, although not necessarily at a specified equilibrium point. This paper presents the first treatment of semistability for matrix second-order systems.
Disease Status at Diagnosis in Danish Children with α1-antitrypsin Deficiency

Objectives: The aim of this cross-sectional study was to assess the state of disease at the time of diagnosis in Danish children with α1-antitrypsin deficiency as Denmark has a high prevalence of ZZ-homozygosity. Methods: Children either heterozygous, compound heterozygous, or homozygous for Z- and S-variants in the SERPINA1-gene were included. Clinical characteristics, SERPINA1-genotype, and blood serum (S) concentrations were recorded concurrently with genetic testing. Serum liver marker concentrations were compared using T tests and Wilcoxon-Mann-Whitney tests. Generalized estimating equation (GEE) linear regression models, both univariable and multivariable adjusted for age and sex, were applied to identify correlations with serum α1-antitrypsin (S-AAT). The relationship between S-AAT concentration and genotype was assessed using logistic regression with GEE. Results: The study included 183 of 225 children genetically tested for alpha-1-antitrypsin deficiency (AATD). Of these, 36.6% were homozygous for the Z-variant. Of the heterozygotes, 89.7% had a ZM genotype and the remaining had either an MS genotype or were compound heterozygous. At diagnosis, ZZ-homozygous children had higher serum concentrations of liver enzymes and conjugated bilirubin, but lower concentrations of S-AAT compared with heterozygotes. Serum concentrations of conjugated bilirubin and liver enzymes were negatively associated with S-AAT. Children under 6 months of age had higher total S-bilirubin concentrations than children over 6 months of age. Conclusions: A low S-AAT concentration is a strong indicator of homozygosity, and homozygous children have higher enzymatic and cholestatic parameters compared with heterozygous children at diagnosis. This underlines the importance of measuring the S-AAT concentration in children with prolonged neonatal jaundice.
Enumerating the total number of subtrees of trees

Over some types of trees with a given number of vertices, which trees minimize or maximize the total number of subtrees or leaf containing subtrees are studied. Here are some of the main results:\ (1)\, Sharp upper bound on the total number of subtrees (resp. leaf containing subtrees) among $n$-vertex trees with a given matching number is determined; as a consequence, the $n$-vertex tree with domination number $\gamma$ maximizing the total number of subtrees (resp. leaf containing subtrees) is characterized. (2)\, Sharp lower bound on the total number of leaf containing subtrees among $n$-vertex trees with maximum degree at least $\Delta$ is determined; as a consequence the $n$-vertex tree with maximum degree at least $\Delta$ having a perfect matching minimizing the total number of subtrees (resp. leaf containing subtrees) is characterized. (3)\, Sharp upper (resp. lower) bound on the total number of leaf containing subtrees among the set of all $n$-vertex trees with $k$ leaves (resp. the set of all $n$-vertex trees of diameter $d$) is determined.
Population PK and Semimechanistic PK/PD Modeling and Simulation of Relugolix Effects on Testosterone Suppression in Men with Prostate Cancer

Relugolix, the first orally active, nonpeptide gonadotropin‐releasing hormone receptor antagonist, is approved in the United States and the European Union for the treatment of adult patients with advanced prostate cancer. The recommended dosing regimen is a 360‐mg loading dose followed by a 120‐mg daily dose. Relugolix and testosterone concentration data and clinical information from two phase I studies, two phase II studies, and the phase III safety and efficacy study (HERO) were used to develop a population pharmacokinetic (PopPK) model and a semimechanistic population pharmacokinetic/pharmacodynamic (PopPK/PD) model that characterized relugolix exposure and its relationship to testosterone concentrations. Age, body weight, and Black/African American race had at most minimal effects on relugolix exposure or testosterone concentrations with no clinical relevance. Simulations using the PopPK/PD model confirmed the recommended dosing regimen of relugolix, with the median simulated testosterone concentrations predicted to achieve castration levels (< 50 ng/dL) and profound castration levels (< 20 ng/dL) by day 2 and day 9, respectively, and demonstrated that 97.3% and 85.5% of the patients remained at castration levels (< 50 ng/dL) upon temporary interruption of treatment for 7 days and 14 days, respectively. Collectively, simulations based on the PopPK and PopPK/PD models were consistent with actual data from clinical studies, reflecting the high predictiveness of the models and supporting the reliability of model‐based simulations. These models can be used to provide guidance regarding dosing recommendations under various circumstances (e.g., temporary interruption of treatment, if needed) for relugolix.