Miracle-dz/UniFAR-FTUs huggingface dataset:
Challenges and Potential Opportunities of Mobile Phone Call Detail Records in Health Research: Review

Background Call detail records (CDRs) are collected by mobile network operators in the course of providing their service. CDRs are increasingly being used in research along with other forms of big data and represent an emerging data type with potential for public good. Many jurisdictions have infrastructures for health data research that could benefit from the integration of CDRs with health data. Objective The objective of this study was to review how CDRs have been used in health research and to identify challenges and potential opportunities for their wider use in conjunction with health data. Methods A literature review was conducted using structured search terms making use of major search engines. Initially, 4066 items were identified. Following screening, 46 full text articles were included in the qualitative synthesis. Information extracted included research topic area, population of study, datasets used, information governance and ethical considerations, study findings, and data limitations. Results The majority of published studies were focused on low-income and middle-income countries. Making use of the location element in CDRs, studies often modeled the transmission of infectious diseases or estimated population movement following natural disasters with a view to implementing interventions. CDRs were used in anonymized or aggregated form, and the process of gaining regulatory approvals varied with data provider and by jurisdiction. None included public views on the use of CDRs in health research. Conclusions Despite various challenges and limitations, anonymized mobile phone CDRs have been used successfully in health research. The use of aggregated data is a safeguard but also a further limitation. Greater opportunities could be gained if validated anonymized CDRs were integrated with routine health records at an individual level, provided that permissions and safeguards could be put in place. Further work is needed, including gaining public views, to develop an ethically founded framework for the use of CDRs in health research.
Interferon-α–Mediated Activation of T Cells from Healthy and HIV-Infected Individuals Is Suppressed by Δ9-Tetrahydrocannabinol

Patients with HIV routinely use medicinal cannabinoids to treat neuropathic pain, anxiety, and human immunodeficiency virus (HIV)–associated wasting. However, Δ9-tetrahydrocannabinol (THC), the primary psychoactive cannabinoid in cannabis, suppresses T-cell function and secretion of interferons, both critically important in the antiviral immune response. Interferon-α (IFNα), a key cytokine in T-cell activation and peripheral control of HIV infection, can potentiate responsiveness to interleukin-7 (IL-7), a crucial homeostatic cytokine for peripheral T-cell maintenance. The objective of this investigation was to compare the response of T cells to stimulation by IFNα and IL-7 in T cells from healthy and HIV+ donors in the absence and presence of THC. To compare T-cell responses between healthy and HIV+ donors signaling through IFNα receptor, IFNα-induced expression of IL-7α receptor (IL-7Rα), cognate signaling through IL-7R, and on IL-7–mediated T-cell proliferation were measured by flow cytometry and real-time quantitative polymerase chain reaction. CD8+ T cells from HIV+ donors showed a diminished response to IFNα-induced phosphorylated signal transducer and activator of transcription-1 activation compared with CD8+ T cells from healthy donors, whereas CD4+ T cells from HIV+ donors and healthy donors were comparable. Treatment with IFNα promoted IL-7R expression and potentiated IL-7–induced STAT5 phosphorylation to augment IL-7–mediated proliferation by T cells from healthy and HIV+ donors. Finally, HIV+ donors exhibited reduced sensitivity to THC-mediated suppression by IFNα- and IL-7–mediated stimulation compared with healthy donors. These results further support THC as being immune suppressive while identifying putatively beneficial aspects of cannabinoid-based therapies in HIV+ patients.
On the joint distribution of the supremum, infimum, and the value of a semicontinuous process with independent increments

The joint distribution of the supremum, inﬁmum, and the value of a homogeneous lower semicontinuous process with independent increments is found in this paper.Theweak convergence of the boundary distribution to the corresponding distribution of the Wiener process is proved in the case of E ξ (1) = 0 and E ξ 2 (1) < ∞ . Exact and asymptotic relations are obtained for this distribution.
Live attenuated influenza vaccine viral vector induces functional cytotoxic T-cell immune response against foreign CD8+ T-cell epitopes inserted into NA and NS1 genes using the 2A self-cleavage site

ABSTRACT The development of viral vector vaccines against various pathogens for which conventional vaccination approaches are not applicable has been a priority for a number of years. One promising approach is the insertion of immunodominant conservative cytotoxic T-cell (CTL) epitopes into the genome of a viral vector, which then delivers these epitopes to target cells, inducing immunity. Many different viruses have been assessed as viral vectors for CTL-based vaccines, but only a few of them are clinically relevant, mainly because of safety issues and limited knowledge about their performance in humans. In this regard, the use of licensed cold-adapted live attenuated influenza vaccine (LAIV) viruses as a vector delivery system has clear advantages for CTL-based vector vaccines against other respiratory pathogens: LAIV is known to induce all arms of the adaptive immune system and is administered via nasal spray, and its production process is relatively easy and inexpensive. Here we present the first results of the use of an LAIV backbone for designing a CTL epitope-based vaccine against respiratory syncytial virus (RSV). The chimeric LAIV-RSV vaccine candidates were attenuated in mice and induced strong, fully functional CTL immunity in this animal model.
Twins Reared Apart and Twins in Families: The Findings Behind the Fascination

Dr. Irving I. Gottesman was very creative in applying twin research designs to test hypotheses and predictions about human behavior. Two designs stand out among others: twins reared apart from birth and the twin-family study. I (NS) was inspired to incorporate both of these approaches into my own research programs at California State University, Fullerton. Gottesman's involvement and contributions to reared-apart twin research are described, followed by selected findings from the Minnesota Study of Twins Reared Apart (MISTRA), the Fullerton Study of Chinese Twins Reared Apart (CTA), a case report on separated monozygotic (MZ) female twins from South Korea, and doubly exchanged MZ male twin pairs from Colombia, South America. Recent findings from an ongoing twin-family study of social closeness, and future directions, are also presented.
Evaluations of Urban Sovereign Citizens' Competency to Stand Trial

There are few studies of sovereign citizens undergoing competency-to-stand-trial evaluations and little has been written about African-American or urban sovereign citizens. In this study, we examined competency-to-stand-trial reports of 36 New York City defendants who declared themselves to be sovereign citizens during their evaluations. All were men and 33 were African American. The majority denied recent or remote histories of psychiatric hospitalizations or substance use. Sixty-nine percent were deemed competent. Compared with those deemed competent, those deemed not competent were significantly more likely to have diagnosed psychotic disorders and to have reported histories of psychiatric hospitalizations. The 36 who declared themselves sovereign citizens were compared with 200 who did not, from a study conducted in the same forensic clinic. The sovereign citizens were significantly more likely to be male, African American, and high school graduates and were significantly less likely to report a history of psychiatric hospitalization or substance use. Compared with the nonsovereign citizens, they were less likely to receive a diagnosis of psychotic or mood disorders during the competency evaluation and were more likely to be deemed competent. Included are suggestions to assist forensic examiners conducting evaluations of these difficult cases.
Combined treatment with GSNO and CAPE accelerates functional recovery via additive antioxidant activities in a mouse model of TBI

Traumatic brain injury (TBI) is the major cause of physical disability and emotional vulnerability. Treatment of TBI is lacking due to its multimechanistic etiology, including derailed mitochondrial and cellular energy metabolism. Previous studies from our laboratory show that an endogenous nitric oxide (NO) metabolite S‐nitrosoglutathione (GSNO) provides neuroprotection and improves neurobehavioral function via anti‐inflammatory and anti‐neurodegenerative mechanisms. To accelerate the rate and enhance the degree of recovery, we investigated combining GSNO with caffeic acid phenethyl ester (CAPE), a potent antioxidant compound, using a male mouse model of TBI, controlled cortical impact in mice. The combination therapy accelerated improvement of cognitive and depressive‐like behavior compared with GSNO or CAPE monotherapy. Separately, both GSNO and CAPE improved mitochondrial integrity/function and decreased oxidative damage; however, the combination therapy had greater effects on Drp1 and MnSOD. Additionally, while CAPE alone activated AMPK, this activation was heightened in combination with GSNO. CAPE treatment of normal animals also significantly increased the expression levels of pAMPK, pACC (activation of AMPK substrate ACC), and pLKB1 (activation of upstream to AMPK kinase LKB1), indicating that CAPE activates AMPK via LKB1. These results show that while GSNO and CAPE provide neuroprotection and improve functional recovery separately, the combination treatment invokes greater recovery by significantly improving mitochondrial functions and activating the AMPK enzyme. Both GSNO and CAPE are in human consumption without any known adverse effects; therefore, a combination therapy‐based multimechanistic approach is worthy of investigation in human TBI.
(−)-Homosalinosporamide A and Its Mode of Proteasome Inhibition: An X-ray Crystallographic Study

Upon acylation of the proteasome by the β-lactone inhibitor salinosporamide A (SalA), tetrahydrofuran formation occurs by intramolecular alkylation of the incipient alkoxide onto the choroethyl sidechain and irreversibly blocks the active site. Our previously described synthetic approach to SalA, utilizing a bioinspired, late-stage, aldol-β-lactonization strategy to construct the bicyclic β-lactone core, enabled synthesis of (–)-homosalinosporamide A (homoSalA). This homolog was targeted to determine whether an intramolecular tetrahydropyran is formed in a similar manner to SalA. Herein, we report the X-ray structure of the yeast 20S proteasome:homoSalA-complex which reveals that tetrahydropyran ring formation does not occur despite comparable potency at the chymotrypsin-like active site in a luminogenic enzyme assay. Thus, the natural product derivative homoSalA blocks the proteasome by a covalent reversible mode of action, opening the door for further fine-tuning of proteasome inhibition.
Denitrosylate and live longer: how ADH5/GSNOR links mitophagy to aging

ABSTRACT Mitochondrial dynamics is required to adapt the manifold functions of mitochondria to cell needs and regulate their turnover by mitophagy. Actually, only if fragmented, mitochondria are engulfed by phagophores, the precursors to autophagosomes, and subsequently degraded. This process is essential to maintain a correct and healthy number of mitochondria that, otherwise, might be harmful. They, indeed, represent the main source of reactive oxygen species that – according to the mitochondrial free radical theory of aging – can cause aging when chronically overproduced. In a recent study, we demonstrated that S-nitrosylation, the reversible modification of cysteine residues by nitric oxide (NO), hyperactivates mitochondrial fragmentation by targeting DNM1L/Drp1 (dynamin 1-like) at Cys644, but inhibits mitophagy, the concomitant occurrence of these conditions driving cell senescence. We demonstrated that cell senescence, as well as mouse and human aging are characterized by an epigenetically-driven decrease in ADH5/GSNOR (alcohol dehydrogenase 5 [class III], chi polypeptide), suggesting that ADH5 may act as new longevity gene.
Alveolar bone resorption and Th1/Th17‐associated immune response triggered during Aggregatibacter actinomycetemcomitans‐induced experimental periodontitis are serotype‐dependent

BACKGROUND Aggregatibacter actinomycetemcomitans expresses several virulence factors that may contribute to the pathogenesis of periodontitis. Based on the antigenicity of the O-polysaccharide component of the lipopolysaccharide (LPS), different A. actinomycetemcomitans serotypes have been described. Among them, serotype b has demonstrated a stronger capacity to trigger Th1 and Th17-associated cytokine, CC-chemokine, and CC-chemokine receptor production on immune cells in vitro. With a murine model of experimental periodontitis, this investigation aimed to analyze the alveolar bone resorption and the pattern of immune response triggered by the different A. actinomycetemcomitans serotypes within periodontal lesions. METHODS For periodontal lesion induction, mice were orally infected with the different A. actinomycetemcomitans serotypes or their purified LPS. Alveolar bone resorption was analyzed using microcomputed tomography and scanning electron microscopy. Bacterial infection, receptor activator of nuclear factor-kappa B ligand (RANKL) and Th1 and Th17-associated cytokine, CC-chemokine, and CC-chemokine receptor levels were quantified by quantitative polymerase chain reaction (qPCR). T lymphocytes isolated from periodontal lesions were analyzed by flow cytometry. RESULTS In periodontal lesions, serotype b of A. actinomycetemcomitans induced higher alveolar bone resorption and expression of RANKL compared with the other serotypes. In addition, serotype b induced greater levels of Th1- and Th17-related cytokines, CC-chemokines, and CC-chemokine receptors than the others. Similarly, higher numbers of infiltrating Th1 and Th17 lymphocytes were detected in serotype b-induced periodontal lesions. CONCLUSIONS These results demonstrate that periodontal lesions induced with different A. actinomycetemcomitans serotypes elicited distinct alveolar bone resorption and immune response. In particular, serotype b was more pathogenic than the others and induced stronger Th1 and Th17 patterns of immune responses during experimental periodontitis.
Early Regenerative Capacity in the Porcine Heart

Background: The adult mammalian heart has limited ability to repair itself after injury. Zebrafish, newts, and neonatal mice can regenerate cardiac tissue, largely by cardiac myocyte (CM) proliferation. It is unknown whether hearts of young large mammals can regenerate. Methods: We examined the regenerative capacity of the pig heart in neonatal animals (ages 2, 3, or 14 days postnatal) after myocardial infarction or sham procedure. Myocardial scar and left ventricular function were determined by cardiac magnetic resonance imaging and echocardiography. Bromodeoxyuridine pulse-chase labeling, histology, immunohistochemistry, and Western blotting were performed to study cell proliferation, sarcomere dynamics, and cytokinesis and to quantify myocardial fibrosis. RNA-sequencing was also performed. Results: After myocardial infarction, there was early and sustained recovery of cardiac function and wall thickness in the absence of fibrosis in 2-day-old pigs. In contrast, older animals developed full-thickness myocardial scarring, thinned walls, and did not recover function. Genome-wide analyses of the infarct zone revealed a strong transcriptional signature of fibrosis in 14-day-old animals that was absent in 2-day-old pigs, which instead had enrichment for cytokinesis genes. In regenerating hearts of the younger animals, up to 10% of CMs in the border zone of the myocardial infarction showed evidence of DNA replication that was associated with markers of myocyte division and sarcomere disassembly. Conclusions: Hearts of large mammals have regenerative capacity, likely driven by cardiac myocyte division, but this potential is lost immediately after birth.
Diabetes mellitus and laboratory medicine in sub-Saharan Africa: challenges and perspectives

ABSTRACT Diabetes mellitus is an increasing public health problem in sub-Saharan Africa with a substantial socioeconomic burden. Although laboratory medicine has been recognized as one of the six key public health functions, there are still gaps in strengthening of laboratory services in developing countries. In the last decades, a lot of progress has been made in the diagnostic field of infectious diseases, whereas the diagnosis of noncommunicable diseases is still insufficient and uneven. This article analyses the challenges encountered in diagnosing and monitoring of diabetes mellitus in sub-Saharan Africa and explores new alternative diagnostic tools.
Novel T7 Phage Display Library Detects Classifiers for Active Mycobacterium Tuberculosis Infection

Tuberculosis (TB) is caused by Mycobacterium tuberculosis (MTB) and transmitted through inhalation of aerosolized droplets. Eighty-five percent of new TB cases occur in resource-limited countries in Asia and Africa and fewer than 40% of TB cases are diagnosed due to the lack of accurate and easy-to-use diagnostic assays. Currently, diagnosis relies on the demonstration of the bacterium in clinical specimens by serial sputum smear microscopy and culture. These methods lack sensitivity, are time consuming, expensive, and require trained personnel. An alternative approach is to develop an efficient immunoassay to detect antibodies reactive to MTB antigens in bodily fluids, such as serum. Sarcoidosis and TB have clinical and pathological similarities and sarcoidosis tissue has yielded MTB components. Using sarcoidosis tissue, we developed a T7 phage cDNA library and constructed a microarray platform. We immunoscreened our microarray platform with sera from healthy (n = 45), smear positive TB (n = 24), and sarcoidosis (n = 107) subjects. Using a student t-test, we identified 192 clones significantly differentially expressed between the three groups at a False Discovery Rate (FDR) <0.01. Among those clones, we selected the top ten most significant clones and validated them on independent test set. The area under receiver operating characteristics (ROC) for the top 10 significant clones was 1 with a sensitivity of 1 and a specificity of 1. Sequence analyses of informative phage inserts recognized as antigens by active TB sera may identify immunogenic antigens that could be used to develop therapeutic or prophylactic vaccines, as well as identify molecular targets for therapy.
Lyme Disease Transmission Risk: Seasonal Variation in the Built Environment

Seasonal variation in spatial distribution and pathogen prevalence of Borrelia burgdorferi in blacklegged ticks (Ixodes scapularis) influences human population risk of Lyme disease in peri-urban built environments. Parks, gardens, playgrounds, school campuses and neighborhoods represent a significant risk for Lyme disease transmission. From June 2012 through May 2014, ticks were collected using 1 m2 corduroy cloths dragged over low-lying vegetation parallel to walkways with high human foot traffic. DNA was extracted from ticks, purified and presence of B. burgdorferi assessed by polymerase chain reaction amplification. Summer is reported as the time of highest risk for Lyme disease transmission in the United States and our results indicate a higher tick density of 26.0/1000 m2 in summer vs. 0.2/1000 m2 to 10.5/1000 m2 in spring and fall. However, our findings suggest that tick infection rate is proportionally higher during the fall and spring than summer (30.0–54.7% in fall and 36.8–65.6% in spring vs. 20.0–28.2% in summer). Seasonal variation in infected tick density has significant implications for Lyme disease transmission as people are less likely to be aware of ticks in built environments, and unaware of increased infection in ticks in spring and fall. These factors may lead to more tick bites resulting in Lyme infection.
The Use of Qualitative Behaviour Assessment for the On-Farm Welfare Assessment of Dairy Goats

Simple Summary The use of feasible indicators to evaluate animals’ emotional states in farm animals is strongly encouraged for welfare assessment. The inclusion of qualitative behaviour assessment (QBA) in on-farm protocols has been constantly increasing during the last few years; but its association with other welfare measures has been scarcely investigated so far. In the present study; we investigated whether QBA shows a meaningful coherence with other measures included in the AWIN (Animal Welfare Indicators) welfare assessment protocol for dairy goats. We confirmed that QBA can clearly discern mood (from Agitated/Alert to Content/Relaxed) and the level of activity (from Bored to Lively) in goats. Furthermore; goats with a shiny hair coat seem more relaxed and sociable than goats with a poor hair coat condition. In contrast; farms where the workload for the stockperson is high have goats that were observed as more bored and suffering; probably because farmers do not invest enough time in taking care of their animals. Even though we found only few relations between QBA and the other measures of the AWIN welfare assessment protocol; the holistic approach of QBA can be useful to integrate the assessment and give a different perspective on the complexity of animals’ emotions and overall welfare state. Abstract This research investigated whether using qualitative behaviour assessment (QBA) with a fixed list of descriptors may be related to quantitative animal- (ABM) and resource-based (RBM) measures included in the AWIN (Animal Welfare Indicators) welfare assessment prototype protocol for goats, tested in 60 farms. A principal component analysis (PCA) was conducted on QBA descriptors; then PCs were correlated to some ABMs and RBMs. Subsequently, a combined PCA merged QBA scores, ABMs and RBMs. The study confirms that QBA can identify the differences in goats’ emotions, but only few significant correlations were found with ABMs and RBMs. In addition, the combined PCA revealed that goats with a normal hair coat were scored as more relaxed and sociable. A high farm workload was related to bored and suffering goats, probably because farmers that can devote less time to animals may fail to recognise important signals from them. Goats were scored as sociable, but also alert, in response to the presence of an outdoor run, probably because when outdoors they received more stimuli than indoors and were more attentive to the surroundings. Notwithstanding these results, the holistic approach of QBA may allow to register animals’ welfare from a different perspective and be complementary to other measures.