Miracle-dz/UniFAR-FTUs huggingface dataset:
RECONSTRUCTING THE EARLY COURSE OF SCHIZOPHRENIA AND ITS CONSEQUENCES

World Psychiatry 5:3 October 2006 In the last two decades, widespread attention has been accorded to the insight that, in psychosis, the first contact with mental health services is frequently preceded by a period of evolving disorder whose duration is of several years (1-5). Early recognition and early intervention have fanned hopes of preventing or postponing psychosis onset, reducing severity of illness or at least ameliorating the personal and social consequences involved. In the wake of the pioneering work of McGorry and his Melbournebased group, early recognition and intervention centres for psychosis have sprung up in many countries (6). Kraepelin (7) already described “minor changes in mood, which may be recurrent or persist for weeks, months or even for years as the only premonitory signs of an imminent mental disorder”. The first systematic analyses of the prodrome of schizophrenia were conducted by Sullivan (8) and Cameron (9,10), with the aim of initiating early intervention, but these attempts failed. After World War II, Conrad (11) and Docherty et al (12) proposed stage models of evolving illness, but these models could not be adequately replicated (13) and failed to offer an opportunity for developing effective approaches to early intervention. In the past two decades, a series of instruments for the early recognition of schizophrenia have been developed. Their aim was the identification of persons at a high enough risk for psychosis to permit diagnostic discrimination and justify early intervention. Because populationbased prospective studies of onset and early illness course are impractical, due to the low incidence rate of schizophrenia and the high frequency of an uncharacteristic type of onset, these instruments were developed on the basis of retrospective studies. The psychopathological phenomena that can be used for early diagnostic discrimination and/or for predicting the onset of a psychotic episode in practice include: a) characteristic prodromal signs and symptoms; b) neuropsychological deficits assessed in cognitive tests (14); c) characteristics of the illness course. Potent biological markers that would facilitate the early recognition of psychotic disorders are not yet available. In the Edinburgh high-risk study (15) and the Melbournebased early-intervention programme (16), high-risk probands who transited to psychosis showed a significant volume reduction in the hippocampus-parahippocampus area in comparisons with high-risk probands without transition to psychosis. This finding of high theoretical interest, however, cannot yet be harnessed in practice.
HIV and AIDS Relative to Other Health, Social, and Relationship Concerns Among Low-Income Urban Women

Objective—To determine the priorities of low-income women regarding health, relationship, and social concerns. Method—Street-intercept surveys conducted with 161 low-income urban women (M = 27 years; 85% African-American; 80% single mothers) regarding their perceptions of the threat associated with 48 health and social problems. Results—Women rated AIDS as their most important health, social, or relationship concern; nearly one-half of all women indicated that they would attend risk reduction programs to learn how to avoid infection with HIV. Conclusions—AIDS is perceived as a serious threat to women’s health, and that interventions to reduce risk are welcomed.
A Liposomal Model That Mimics the Cutaneous Production of Vitamin D 3 STUDIES OF THE MECHANISM OF THE MEMBRANE-ENHANCED THERMAL ISOMERIZATION OF PREVITAMIN D 3 TO VITAMIN D 3 *

We reported previously that the rate of previtamin D 3 (preD 3 ) º vitamin D 3 isomerization was enhanced by about 10 times in the skin compared with that in organic solvents. To elucidate the mechanism by which the rate of this reaction is enhanced in the skin, we developed a liposomal model that mimicked the enhanced isomerization of preD 3 to vitamin D 3 that was described in human skin. Using this model we studied the effect of changing the polarity of preD 3 as well as changing the chain length and the degree of saturation of liposomal phospholipids on the kinetics of preD 3 º vitamin D 3 isomer- ization. We found that a decrease in the hydrophilic interaction of the preD 3 with liposomal phospholipids by an esterification of the 3 b -hydroxy of preD 3 (previta-min D 3 -3 b -acetate) reduced the rate of the isomerization by 67%. The addition of a hydroxyl on C-25 of the hydrophobic side chain (25-hydroxyprevitamin D 3 ), which de- creased the hydrophobic interaction of preD 3 with the phospholipids, reduced the rate by 87%. In contrast, in an isotropic n -hexane solution, there was little differ-ence among the rates of the conversion of preD 3 , its 3 b -acetate, and 25-hydroxy derivatives to their corresponding vitamin D 3 compounds. We also determined rate constants ( k ) of preD 3 º vitamin D 3 isomerization in liposomes containing phosphatidylcholines with different
Blood Vessel Morphological Changes as Visualized by MRA During Treatment of Brain Metastases: A Feasibility Study

Purpose—To prospectively determine a) if magnetic resonance angiograms (MRA) can detect intracranial vascular morphological changes during treatment of brain metastases from breast cancer, and b) if serial, quantitative vessel tortuosity measurements might predict tumor treatment response in advance of traditional methods. Materials and Methods—Institutional review board approval and informed consent were obtained in this HIPAA-compliant study. Twenty-two women aged 31–61 underwent brain MRA imaging prior to and two months after initiation of lapatinib therapy for brain metastases from breast cancer. Vessels were extracted from MRA using a computer program. Changes in vessel number, radius, and tortuosity were calculated mathematically, were normalized by values defined from 34 healthy controls (19 females, 15 males, age range 19–72), and were compared to subsequent assessments of tumor volume and clinical course. Results—All tumor patients exhibited abnormal vessel tortuosity at baseline. Nineteen patients (86%) failed to exhibit improvement in vessel tortuosity at month 2 and all demonstrated tumor growth by month 4. Vessel tortuosity measurements correctly predicted treatment failure 1–2 months earlier than traditional methods. Three patients (14%) displayed quantitative improvement in vessel tortuosity at month 2, with dropout of small abnormal vessels and “straightening” of large vessels. The two patients for whom further follow-up was available each responded to treatment for over 6 months. Conclusion—Our results establish the feasibility of using MRA to quantify vessel shape changes during therapy. Although further research is required, results suggest that changes in vessel tortuosity might provide an early prediction of tumor treatment response.
Eukaryotic RNAs : Once More from the Beginning

I am profoundly grateful to the American Society for Cell Biology for the award to me and my colleague Sheldon Penman of the E.B. Wilson Medal. This occasion presents the opportunity for reflections on a 40year search for indications of how RNA functions as an informational molecule in eukaryotic cells. As will be recounted, this quest began in the late 1950s, before the recognition of mRNA, by studying the biosynthesis of poliovirus, an RNA virus. The search continued through the molecular and biochemical definition of classes of nuclear and cytoplasmic RNA in both growing and virus-infected cultured mammalian cells and, subsequently, through studies on the basis of cellspecific mRNA expression in the liver. Finally, in the recent past our laboratory has concentrated on our original goal, the mechanism of recognition of extracellular signals with consequent gene regulation in the cell nucleus.
Strain-Polarization Coupling Manifested by Impedance Spectroscopy

The ferroelastic phase in hydrogen-bonded TlH2PO4 was investigated by means of impedance spectroscopy. The temperature-dependent dielectric susceptibility exhibited perfect agreement with that expected for strain-polarization coupling. The high-temperature dielectric susceptibility revealed the corresponding Curie-Weiss temperature to be far above the antiferroelectric phase transition temperature, indicative of a novel mixed phase between the antiferroelectric and the ferroelastic phase transitions.
Development of a piezoelectric energy-harvesting sensor: from concept to reality

This study focuses on the development and integrated design over a 24-month period of a high efficiency energy-harvesting (EH) temperature sensor, based on piezoelectric materials, with applications for the sustainability of smart buildings, structures and infrastructures. The EH sensor, harvests the airflow inside Heating, Ventilation and Air Conditioning (HVAC) systems, using a piezoelectric component and an appropriate customizable aerodynamic fin that takes advantage of specific air flow effects, and is implemented for optimizing the energy consumption in buildings. The project was divided in several work-packages (some running in parallel) that cover different aspects of the device development. Some of them focus on engineering aspects (starting from the numerical modeling, then prototyping, and concluding with experimental testing). Other aspects focus on the sensor promotion (including the development of a business plan, the intellectual property rights, the final design and the go-to-market actions). Considering the multidisciplinary character of the project (involving knowledge from fields such as wind engineering, electrical engineering, industrial design, entrepreneurship), this study tries to provide an insight on the complex design issues that arise when such complex, sometimes conflicting and overlapping aspects have to be managed within strict deadlines. In doing so, the most important design and development aspects are critically presented.
Orthopedic Patients with Mental Disorder: Literature Review on Preoperative and Postoperative Precautions

Because of the increasing global trend of patients with mental disorders, orthopedic surgeons are more likely to encounter orthopedic patients with mental disorders in clinical settings. Identifying the characteristics of these patients and implementing psychiatric management can affect the clinical outcome of orthopedic treatment. Thus, orthopedic surgeons need to assess the psychiatric medical history of orthopedic patients with mental disorders before surgery and understand the psychological and behavioral patterns of patients with mental disorders. In addition, appropriate psychiatric consultations and evaluations are necessary to prevent worsening of mental disorders before and after surgery.
A comprehensive SARS-CoV-2-human protein-protein interactome network identifies pathobiology and host-targeting therapies for COVID-19

Physical interactions between viral and host proteins are responsible for almost all aspects of the viral life cycle and the host’s immune response. Studying viral-host protein-protein interactions is thus crucial for identifying strategies for treatment and prevention of viral infection. Here, we use high-throughput yeast two-hybrid and affinity purification followed by mass spectrometry to generate a comprehensive SARS-CoV-2-human protein-protein interactome network consisting of both binary and co-complex interactions. We report a total of 739 high-confidence interactions, showing the highest overlap of interaction partners among published datasets as well as the highest overlap with genes differentially expressed in samples (such as upper airway and bronchial epithelial cells) from patients with SARS-CoV-2 infection. Showcasing the utility of our network, we describe a novel interaction between the viral accessory protein ORF3a and the host zinc finger transcription factor ZNF579 to illustrate a SARS-CoV-2 factor mediating a direct impact on host transcription. Leveraging our interactome, we performed network-based drug screens for over 2,900 FDA-approved/investigational drugs and obtained a curated list of 23 drugs that had significant network proximities to SARS-CoV-2 host factors, one of which, carvedilol, showed promising antiviral properties. We performed electronic health record-based validation using two independent large-scale, longitudinal COVID-19 patient databases and found that carvedilol usage was associated with a significantly lowered probability (17%−20%, P < 0.001) of obtaining a SARS-CoV-2 positive test after adjusting various confounding factors. Carvedilol additionally showed anti-viral activity against SARS-CoV-2 in a human lung epithelial cell line [half maximal effective concentration (EC50) value of 4.1 μM], suggesting a mechanism for its beneficial effect in COVID-19. Our study demonstrates the value of large-scale network systems biology approaches for extracting biological insight from complex biological processes.
Gender dimensions of COVID-19 preventive policies: a global perspective

The COVID-19 pandemic has had an impact on the global population not just from morbidity and mortality associated with SARS-CoV-2 infection, but also due to measures imposed upon populations to slow the transmission and prevent infections. Measures introduced by policymakers have included self-isolation of infective or potentially infective individuals, social distancing, travel bans, school closures, and mandatory face coverings. Most recently, the introduction of vaccination has been a key preventative measure encouraged by many governments. Considering gender differences in adherence to these measures is important to help guide future policymaking and targeting of advice. Differences also arise in how the preventative measures impact different genders. Some policies have caused greater harm to women, compounding existing problems such as inequality in the paid workforce, sexual- and gender-based violence, and inadequate maternal healthcare. Policymakers must consider the gender differences in response to preventive measures and creating effective and equitable policy.
Evaluating Behavioral Risk Factor Interventions for Hypertensive and Diabetic Patient Management in the National Basic Public Health Service Programs from 2009

In recent decades, China has faced a double burden of infectious diseases and noncommunicable diseases (NCDs). The number of deaths due to NCDs accounts for 88.5% of total deaths in China in 2019. To address these public health issues and improve the accessibility and affordability of primary health care, a National Basic Public Health Service Program (NBPHSP) was introduced as part of China’s healthcare reform initiated in 2009. Subsided by national and local government budgets, NBPHSP is mainly implemented by community and township health service centers, as well as health stations in urban areas and village clinics in rural areas (1). Health management of patients with hypertension and diabetes is an integral and pivotal part of the NBPHSP. The National Health Commission successively promulgated the National Standards for Basic Public Health Services (2009, 2011, and 2017 editions) to guide the management of patients with hypertension and diabetes. As required, all primary health care institutions should provide services for detection, comprehensive treatment, and follow-up for the local hypertensive and diabetic residents above 35 years old (2). Lifestyle and behavior risk factor interventions are cost-effective to tackle NCDs and are fundamental components of hypertension and diabetes management in the NBPHSP. Yet, limited literature has evaluated its implementation in China. Therefore, this study used pragmatic approaches to recollect published data and evaluate the implementation of the behavioral risk factor intervention in NCD patients in this nationwide public health action.
The FCRL3 −169CT promoter SNP, which is associated with SLE in Japanese, predicts receptor protein expression on CD19+ B cells

Recently a C>T SNP at position −169 (rs7528684) in the promoter region of the FCRL3 gene was shown to be associated with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and other autoimmune disorders in a Japanese population (1,2). The −169C allele, which was overrepresented in SLE patients confers a more orthodox consensus binding site for the NF-kB transcription factor, increasing promoter activity in vitro and upregulating FCRL3 mRNA transcription. However, the relationship between −169CT alleles and FCRL3 expression on the B cell surface has remained unexplored. Since there is a strong association between the −169CT alleles and FCRL3 mRNA expression, we used a newly developed anti-FCRL3 monoclonal antibody (3D2) (3) to explore the relationship between the −169CT alleles and FCRL3 protein expression on B lymphocytes from diseasefree individuals and SLE patients with inactive disease.
Estimation of Posterior Probabilities Using Multivariate Smoothing Splines and Generalized Cross-Validation.

Abstract : A nonparametric estimate for the posterior probabilities in the classification problem using multivariate smoothing splines is proposed. This estimate presents a nonparametric alternative to logistic discrimination and to survival curve estimation. It is useful in exploring properties of the data and in presenting them in a way comprehensible to the layman. The estimate is obtained as the solution to a constrained minimization problem in a reproducing kernel Hilbert space. It is shown that under certain conditions an estimate exists and is unique.
Ion channels and ion selectivity Essays in Biochemistry

Specific macromolecular transport systems, ion channels and pumps, provide the pathways to facilitate and control the passage of ions across the lipid membrane. Ion channels provide energetically favorable passage for ions to diffuse rapidly and passively according to their electrochemical potential. Selective ion channels are essential for the excitability of biological membranes: the action potential is a transient phenomenon that reflects the rapid opening and closing of voltage-dependent Na+-selective and K+-selective channels. One of the most critical functional aspects of K+ channels is their ability to remain highly selective for K+ over Na+ while allowing high-throughput ion conduction at a rate close to the diffusion limit. Permeation through the K+ channel selectivity filter is believed to proceed as a “knock-on” mechanism in which 2–3 K+ ions interspersed by water molecules move in single file. Permeation through the comparatively wider and less selective Na+ channels also proceeds via a loosely coupled knock-on mechanism, although the ions do not need to be fully dehydrated. While simple structural concepts are often invoked to rationalize the mechanism of ion selectivity, a deeper analysis shows that subtle effects play an important role in these flexible dynamical structures.
Eligibility Criteria Can Substantially Infl uence the Results of Alcohol-Treatment Outcome Research *

757 ABSTRACT. Objective: Most alcohol-treatment studies exclude some patients from participation based on particular criteria (e.g., comorbid illegal drug abuse, homelessness). The current study evaluated whether such eligibility criteria can change the outcome results a study obtains. Method: Five widely used treatment research eligibility criteria—(1) psychiatric problems, (2) medical problems, (3) social-residential instability, (4) low motivation/noncompliance, and (5) drug problems—were applied to two samples of real-world alcohol patients whose outcomes were known. Comparing outcomes of the samples with and without the application of eligibility criteria produced estimates of bias in outcome results, as well as an assessment of change in statistical power. Results: Medical and psychiatric eligibility criteria produced a moderate bias in outcome estimates (e.g., a 10% or less change in outcome results). In contrast, social-residential instability, low motivation/noncompliance, and drug use produced a large (e.g., up to an 18% change) to a very large (e.g., up to a 51% change) bias in outcome estimates. Sensitivity analyses showed that these biases are even larger if eligibility criteria are operationalized in a broad rather than a narrow fashion. Contrary to expectation, eligibility criteria did not produce their theoretically expected benefi t of increased statistical power. Conclusions: Researchers who use eligibility criteria should do so judiciously and interpret outcome results in light of potential bias introduced by the ineligibility of some patients for study enrollment. Efforts to integrate fi ndings across treatment outcome studies should also consider how conclusions might be affected by the eligibility criteria used in different research areas. (J. Stud. Alcohol Drugs 69: 757-764, 2008)
Regulated AMPAR exocytosis through NO modulation of PICK1

The activation of NMDA receptors (NMDARs) triggers long-term changes in AMPA receptormediated synaptic transmission in the CNS. These long-lasting changes occur via the addition or removal of AMPA receptors (AMPARs) at the synaptic membrane and are mediated by a number of regulatory proteins including the GluR2 AMPAR-interacting proteins n-ethylmaleimide sensitive factor (NSF) and Protein Interacting with C Kinase (PICK1). We have shown that the potent activation of NMDARs drives unclustering of PICK1 and PICK1-GluR2 dissociation in dendrites resulting in increased surface delivery of AMPARs. Here we show that the dispersal of PICK1 is mediated by the actions of NSF. We find that elevated NMDAR signaling leads to the S-nitrosylation of NSF and increased NSF-GluR2 association. Both NMDAR-dependent unclustering of PICK1 and the delivery of surface AMPARs is dependent on release of nitric oxide (NO). Our data suggest that NMDAR activation can drive the surface delivery of AMPARs from a pool of intracellular AMPARs retained by PICK1 through the NO-dependent modification of NSF.
A Reactive Inelasticity Theoretical Framework for Modeling Viscoelasticity, Plastic Deformation, and Damage in Fibrous Soft Tissue

Fibrous soft tissues are biopolymeric materials that are made of extracellular proteins, such as different types of collagen and proteoglycans, and have a high water content. These tissues have nonlinear, anisotropic, and inelastic mechanical behaviors that are often categorized into viscoelastic behavior, plastic deformation, and damage. While tissue’s elastic and viscoelastic mechanical properties have been measured for decades, there is no comprehensive theoretical framework for modeling inelastic behaviors of these tissues that is based on their structure. To model the three major inelastic mechanical behaviors of tissue’s fibrous matrix, we formulated a structurally inspired continuum mechanics framework based on the energy of molecular bonds that break and reform in response to external loading (reactive bonds). In this framework, we employed the theory of internal state variables (ISV) and kinetics of molecular bonds. The number fraction of bonds, their reference deformation gradient, and damage parameter were used as state variables that allowed for consistent modeling of all three of the inelastic behaviors of tissue by using the same sets of constitutive relations. Several numerical examples are provided that address practical problems in tissue mechanics, including the difference between plastic deformation and damage. This model can be used to identify relationships between tissue’s mechanical response to external loading and its biopolymeric structure. [DOI: 10.1115/1.4041575]