Miracle-dz/UniFAR-FTUs huggingface dataset:
Alexithymia Is Associated With Increased Cardiovascular Mortality in Middle-Aged Finnish Men

Objective: To explore the associations between alexithymia and increased somatic morbidity. The mechanisms underlying these associations, however, are still unclear. Furthermore, data on the association between alexithymia and mortality are scarce. Methods: A total of 2321 Finnish men, aged 46 to 61 years, were followed up for an average of 20 years. Mortality rates were obtained from the national register. The associations between baseline alexithymia and cardiovascular disease (CVD), all-cause, injury, and cancer deaths were examined with adjustments for age and several behavioral (smoking, alcohol consumption, physical activity), physiological (low- and high-density lipoprotein cholesterol, body mass index, systolic blood pressure, history of CVD), and psychosocial (marital status, education, depression) factors. Results: After all adjustments, the risk of CVD death was increased by 1.2% for each 1-point increase in Toronto Alexithymia Scale-26 scores. Conclusions: Alexithymia is associated with increased cardiovascular mortality. BDI = Beck Depression Inventory; BMI = body mass index; CI = confidence interval; CVD = cardiovascular disease; HDL-C = high-density lipoprotein cholesterol; HPL Depression Scale = Human Population Laboratory Depression Scale; LDL-C = low-density lipoprotein cholesterol; RR = risk ratio; TAS = Toronto Alexithymia Scale.
Behavioral and physiological traits of migrant and resident white-crowned sparrows: a common garden approach

ABSTRACT To accommodate a migratory life history, migrants express a greater number of physiological and behavioral stages per annum than residents and are thus considered to have higher finite state diversity (FSD). To investigate the physiological mechanisms and constraints associated with migration, direct comparison of two subspecies of white-crowned sparrow – migrant, Zonotrichia leucophrys gambelii, and resident, Z. l. nuttalli – were made under common garden conditions of photoperiod and housing, as birds progressed from winter through the vernal life history stages. We tested the hypothesis that migrants (higher FSD) respond differently than residents (lower FSD) to the initial predictive cue, photoperiod, to initiate and integrate the progression of vernal stages of prenuptial molt, migration and development of breeding. If differences in vernal phenology were noted, then the basis for the distinctions was considered genetic. Results indicate that (1) residents had a lower threshold to vernal photoperiod with elevations of plasma androgen, growth and development of reproductive structures preceding those of migrants; (2) only migrants displayed prenuptial molt, preparations for migration and migratory restlessness; and (3) neither baseline nor stress-induced plasma corticosterone differed across subspecies, suggesting energetic demands of the common garden were insufficient to induce a differential adrenocortical response in either subspecies, highlighting the impact of environmental conditions on corticosterone secretion. Thus, in a common garden experiment, Z. l. gambelii responds differently to the initial predictive cue, photoperiod, to initiate and execute the vernal stages of molt, migration and development of breeding in comparison to the shared stage of breeding with Z. l. nuttalli, confirming a genetic basis for the subspecies differences. Summary: Under common garden conditions, comparison of migratory and resident white-crowned sparrows identifies distinctions in their respective responses to environmental cues, primarily photoperiod, leading to diverse life histories.
Inhibition of MKP-1 expression potentiates JNK related apoptosis in renal cancer cells.

PURPOSE Mitogen-activated protein kinases (MAPKs) comprise 3 subgroups, that is extracellular signal-regulated protein kinase, c-Jun N-terminal kinase (JNK) and p38 MAPK (p38). In this study we analyzed the role of JNK as well as the expression of MAPK phosphatase-1 (MKP-1) in renal cancers. MATERIALS AND METHODS Four renal cell carcinoma (RCC) cell lines were used. The effects of anisomycin (JNK activator) and Ro-318220 (MKP-1 expression inhibitor) were analyzed by alamar blue assay. Apoptosis was determined by flow cytometric TUNEL analysis, nuclear morphological alternations and the detection of DNA fragmentation. Changes in MKP-1 expression as well as the activation of extracellular signal-regulated protein kinases and JNK were analyzed by Western blotting. RESULTS All cell lines treated with anisomycin resulted in a transient activation of JNK without inducing apoptosis. Since we hypothesized that elevated MKP-1 expression could possibly prevent persistent JNK activation, Ro-318220 was used. When cells were treated with Ro-318220, MKP-1 expression decreased in Caki-1 and KU 20-01 cells but not in ACHN or 769P cells. Combined treatment of Caki-1 and KU 20-01 cells with anisomycin and Ro-318220 resulted in a decrease in MKP-1 expression concomitant with persistent JNK activation. Apoptosis was induced in each cell line. CONCLUSIONS These results suggest that prevalent MKP-1 expression in RCC contributes to cancer cell survival by attenuating an apoptosis inducing signal cascade via JNK. Since Ro-318220 potentiated JNK related apoptosis, JNK activation by blocking MKP-1 expression may be an effective therapeutic approach to RCC.
Association between oxidative stress and telomere length in Type 1 and Type 2 diabetic patients

Background: Increasing evidence showed that telomere length was shorter in age-related diseases, but the mechanism of this phenomenon is still unclear. Aim: To determine whether telomere shortening occurs in Type 1 diabetes (T1D) and Type 2 diabetes (T2D), and explore the effect of antioxidant status on the telomere length. Subjects and methods: T2D patients (no.=62), T1D patients (no.=34), and non-diabetic subjects used as control (CTL) (no.=40) were included in this study. Leukocyte telomere length ratio (T/S ratio) was measured using a quantitative PCR and analyzed. Antioxidant status was estimated by human 8-hydroxy-desoxyguanosine quantization. Other biomarkers, such as fasting plasma glucose, fasting insulin, glycated hemoglobin (HbA1c) and lipid profile were also measured. Results: Compared with CTL group [T/S ratio (mean±SD), 2.39±0.55], leukocyte telomere length was significantly shorter in T2D group (1.67±0.50) and T1D group (1.77±0.50). 8-OHdG that indicated oxidative stress was significantly higher in T2D (2.99±0.85 ng/ml) and T1D (2.03±0.92 ng/ml) group than in CTL group (0.90±0.46 ng/ml). T/S ratio was significantly negatively correlated with age, waist circumference, waist-to-hip ratio, diastolic blood pressure, fasting plasma glucose, HbA1c, homeostasis model assessment of insulin resistance and 8-OHdG in the whole population. 8-OHdG was independent risk factor for telomere shortening in both T1D (p=0.018) and T2D group (p=0.022). Conclusions: In our study, shorter telomere length and increased oxidative stress were observed in both T1D and T2D. Older people with central obesity, hyperglycemia, insulin resistance and severe antioxidant status tended to have shorter telomere length. In addition, 8-OHdG was an independent predictor for telomere length for both T1D and T2D patients.
Meeting the sexual and reproductive health needs of people living with HIV.

KEY POINTS (1) Sexual expression and the desire for parenthood are central to the lives of most people. Acknowledging these aspirations is essential to vindicating the human rights of people living with HIV. (2) Meeting the sexual health needs of HIV positive people is essential to global HIV prevention efforts. (3) Efforts to provide sexual and reproductive health services to HIV-positive people are impeded worldwide by weak and fragmented health systems and by sexual taboos, gender inequality, and HIV stigma and discrimination. (4) Effective HIV programming demands taking advantage of the perspectives, expertise and accumulated experiences of people living with HIV.
Constrained Bayesian Optimization with Noisy Experiments

Randomized experiments are the gold standard for evaluating the effects of changes to real-world systems. Data in these tests may be difficult to collect and outcomes may have high variance, resulting in potentially large measurement error. Bayesian optimization is a promising technique for efficiently optimizing multiple continuous parameters, but existing approaches degrade in performance when the noise level is high, limiting its applicability to many randomized experiments. We derive an expression for expected improvement under greedy batch optimization with noisy observations and noisy constraints, and develop a quasi-Monte Carlo approximation that allows it to be efficiently optimized. Simulations with synthetic functions show that optimization performance on noisy, constrained problems outperforms existing methods. We further demonstrate the effectiveness of the method with two real-world experiments conducted at Facebook: optimizing a ranking system, and optimizing server compiler flags.
Histology of AlphaCor Skirts: Evaluation of Biointegration

Purpose: To report histologic findings in 14 AlphaCor artificial corneas implanted during clinical trials and subsequently explanted from human subjects following complications, so as to evaluate biointegration within the device skirt. Methods: Explants were fixed and sectioned in paraffin. Histologic findings related to the device skirt were compared with earlier histologic results from animal studies and correlated with clinical histories. Results: Two devices had been removed due to complications related to the optic alone, 11 following stromal melting overlying the biointegratable sponge skirt and 1 due to a retroprosthetic membrane. All devices demonstrated normal skirt porosity. Biointegration was similar to that found in animal studies but qualitatively appeared reduced in the affected areas in patients with overlying stromal melting prior to explantation. Patients with a longer history of melting prior to explantation demonstrated presence of inflammatory cells around the device. Conclusions: Histologic findings of the AlphaCor skirt in humans are consistent with earlier animal studies. This study confirms that biointegration by host fibroblastic cells, with collagen deposition occurs after AlphaCor implantation in humans. In cases in which stromal melting had occurred, biointegration is seen to be reduced. On correlating preoperative clinical factors with biointegration observed histologically, preoperative vascularization appears not to be required for AlphaCor biointegration.
Oxygen transfer modeling and simulations for an industrial continuous airlift fermentor

This article deals with the modeling of the oxygen transfer in an industrial airlift fermentor used for lactic yeast production on whey substrates. The purpose of this study was to improve the understanding of the interactions among the various parameters that govern the oxygen transfer phenomena in this type of fermentor. The reliability of the proposed model is demonstrated. The results of the investigations have been put into practice on the industrial scale and have contributed to monitor better the fermentation process. The model was also used to develop new ways of industrial fermentor design.
Collaboration of JNKs and ERKs in Nerve Growth Factor Regulation of the Neurofilament Light Chain Promoter in PC12 Cells*

Nerve growth factor (NGF) induces transcription-dependent neural differentiation of PC12 cells, and the ERK family of MAPKs has been implicated as the dominant signal pathway that mediates this response. We employed a neurofilament light chain (NFLC) promoter-luciferase (NFLC-Luc) reporter to define the role of the ERKs as well as additional MAPK pathways in NGF induction of this neural specific gene. Constitutive active forms of c-Raf-1, MEKK1 and MKK6, proximal regulators of the ERKs, JNKs, and p38 MAPKs, respectively, all stimulated NFLC-Luc activity. NFLC-Luc activity stimulated by NGF, however, was partially (∼50%) inhibited by the MEK inhibitor, PD098059, or by co-transfection of kinase-inactive MEK1 but not by the p38 MAPK inhibitor, SB203580, indicating a role for the ERKs, but not the p38 MAPKs, in NGF regulation of the NFLC promoter. Importantly, a gain-of-function MKK7-JNK3 fusion protein stimulated NFLC-Luc and synergized with gain-of-function c-Raf-1 to activate the NFLC promoter. In addition, transfection of kinase-inactive forms of MEK1 and MKK7 produced an additive inhibition of NGF-stimulated NFLC-Luc relative to either inhibitor alone. These findings indicate that the ERK and JNK pathways collaborate downstream of the NGF receptor for regulation of the NFLC promoter. Truncation analysis and electromobility shift assays established the requirement for a cAMP-response element/activating transcription factor-like site in the NFLC promoter that minimally interacts with constitutively expressed cAMP-response element-binding protein and JunD as well as c-Jun which is induced by NGF in an ERK-dependent manner. Cumulatively, these findings indicate that the ERK pathway requires collaboration with the JNK pathway for maximal activation of the NFLC gene in PC12 cells through the integrated control of c-Jun function.
Studies of distribution and recurrence of Helicobacter spp. gastric mucosa of dogs after triple therapy.

PURPOSE To analyze the triple antimicrobial therapy in positive Helicobacter spp. dogs and to investigate recurrence. METHODS A total of 20 dogs underwent endoscopy followed by gastric biopsy using the rapid urease test and histopathology stained with Giemsa. Ten animals were treated with triple therapy recommended for humans and divided into control and experimental group. The control group was kept in isolation while the experimental group was placed in contact with positive animals during 60 days. RESULTS The prevalence of infection in animals in this experiment was 100%, and more frequent in the fundus and the gastric body. Therapy for 7 days using clarithromycin, amoxicillin and lansoprazole was effective in 100% of the animals. Recurrence of the infection in 80% of dogs in the experimental group, while the control group remained eradicated after 60 days. CONCLUSION Crowded environments associated with close contact with dogs infected with helicobacter are a determinant for transmission of Helicobacter spp. between canines.
Lack of evidence for linkage of the endothelial cell nitric oxide synthase gene to essential hypertension.

BACKGROUND The basal release of nitric oxide by the endothelium plays an important role in regulating blood flow and pressure and mediates most of the endothelium-dependent vasodilation. Impairment of nitric oxide production by specific inhibitors increases blood pressure in humans, and several reports suggest that hypertensive subjects have a blunted endothelium-dependent vasodilatation that might be secondary to decreased nitric oxide production from the vessel wall. METHODS AND RESULTS To determine whether the endothelial nitric oxide synthase gene is involved in human essential hypertension, we identified informative biallelic and multiallelic markers of this locus and performed case-control and linkage studies in hypertensive subjects and normotensive control subjects. We used the affected sib pair method to test for potential linkage in 145 hypertensive pedigrees (269 sib pairs, 346 subjects) with a highly polymorphic marker of the nitric oxide synthase gene (polymorphism information content of 92%). There was no evidence for linkage among affected siblings. The 95% upper confidence limit of this value suggests that at most 1% of alleles in excess of expected are shared. We also identified two informative biallelic markers of this gene to perform a case-control study on white hypertensive and normotensive subjects. Similar genotype distributions between the two groups were noted for both markers. Estimated haplotype frequencies by maximum likelihood methods combining the two biallelic markers were also similar in both groups. CONCLUSIONS These findings do not suggest that common molecular variants of the endothelial nitric oxide synthase gene are involved in essential hypertension.
Characterizing Human Ion Channels in Induced Pluripotent Stem Cell–Derived Neurons

Neurons derived from human-induced pluripotent stem cells were characterized using manual and automated patch-clamp recordings. These cells expressed voltage-gated Na+ (Nav), Ca2+ (Cav), and K+ (Kv) channels as expected from excitable cells. The Nav current was TTX sensitive, IC50 = 12 ± 6 nM (n = 5). About 50% of the Cav current was blocked by 10 µM of the L-type channel blocker nifedipine. Two populations of the Kv channel were present in different proportions: an inactivating (A-type) and a noninactivating type. The A-type current was sensitive to 4-AP and TEA (IC50 = 163 ± 93 µM; n = 3). Application of γ-aminobutyric acid (GABA) activated a current sensitive to the GABAA receptor antagonist bicuculline, IC50 = 632 ± 149 nM (n = 5). In both devices, comparable action potentials were generated in the current clamp. With unbiased, automated patch clamp, about 40% of the cells expressed Nav currents, whereas visual guidance in manual patch clamp provided almost a 100% success rate of patching “excitable cells. ” These results show high potential for pluripotent stem cell–derived neurons as a useful model for drug discovery, in combination with automated patch-clamp recordings for high-throughput and high-quality drug assessments at human neuronal ion channels in their correct cellular background.
Origin of Whales in Epicontinental Remnant Seas: New Evidence from the Early Eocene of Pakistan

Pakicetus inachus from the early Eocene of Pakistan is the oldest and most primitive cetacean known. The dentition of Pakicetus resembles that of carnivorous mesonychid land mammals as well as middle Eocene cetaceans. The otic region of the cranium lacks characteristic specializations of whales necessary for efficient directional hearing under water. Pakicetus occurs with a land-mammal fauna in fluvial sediments bordering epicontinental Eocene remnants of the eastern Tethys seaway. Discovery of Pakicetus strengthens earlier inferences that whales originated from terrestrial carnivorous mammals and suggests that whales made a gradual transition from land to sea in the early Eocene, spending progressively more time feeding on planktivorous fishes in shallow, highly productive seas and embayments associated with tectonic closure of eastern Tethys.
Acute hepatitis complicating parenteral amiodarone does not preclude subsequent oral therapy.

Accepted for publication 24 January 1997 A 50 year old man was admitted with a four week history of increasing exertional dyspnoea and cough productive of white sputum. Two weeks before admission his exercise tolerance had decreased from two miles to 20 yards. He smoked 20 cigarettes a day and drank 60 units of alcohol a week. He was taking no medication. Initial examination revealed a raised venous pressure, gross peripheral oedema, a smooth tender hepatomegaly (but no cutaneous stigmata of chronic liver disease), a third heart sound, dullness at both bases, and extensive lung crepitations. His pulse was irregular with
T‐cell migration: a naive paradigm?

Naive T cells have long been thought to recirculate exclusively between secondary lymphoid organs via the lymph and blood. Evidence is now emerging that this view may be too simplistic and that naive T cells routinely traffic through non‐lymphoid organs in a manner similar to that of memory T cells, albeit in lower numbers. This represents a fundamental shift in the current paradigm of T‐cell migration through different types of tissue. This review summarizes these recent findings, along with the similarities and differences in migratory properties of naive and memory T cells, and discusses how and why naive T cells might access non‐lymphoid tissues.
Advances of Stem Cell Therapeutics in Cutaneous Wound Healing and Regeneration

Cutaneous wound healing is a complex multiple phase process, which overlaps each other, where several growth factors, cytokines, chemokines, and various cells interact in a well-orchestrated manner. However, an imbalance in any of these phases and factors may lead to disruption in harmony of normal wound healing process, resulting in transformation towards chronic nonhealing wounds and abnormal scar formation. Although various therapeutic interventions are available to treat chronic wounds, current wound-care has met with limited success. Progenitor stem cells possess potential therapeutic ability to overcome limitations of the present treatments as it offers accelerated wound repair with tissue regeneration. A substantial number of stem cell therapies for cutaneous wounds are currently under development as a result of encouraging preliminary findings in both preclinical and clinical studies. However, the mechanisms by which these stem cells contribute to the healing process have yet to be elucidated. In this review, we emphasize on the major treatment modalities currently available for the treatment of the wound, role of various interstitial stem cells and exogenous adult stem cells in cutaneous wound healing, and possible mechanisms involved in the healing process.
k-th Best Device Selection for Scheduling in Wireless Powered Communication Networks

This paper studies the performance of a wireless powered communication network consisting of a finite number of batteryless devices that harvest radio frequency energy. We consider novel selection/scheduling schemes, where the k-th best device is selected for information transmission. The proposed schemes correspond to different complexity and are based on: a) the end-to-end (e2e) signal-to-noise ratio (SNR), b) the energy harvested at the devices, and c) the conventional channel-based max-min selection policy. By considering a non-linear energy harvesting (EH) model, we derive analytical expressions for the outage probability of each selection scheme by using high order statistics. We also consider an asymptotic scenario, where the number of devices increases and analyze the behavior of the system by applying extreme value theory. Due to the saturation effects of the non-linear EH model, the performance of all the proposed schemes converges to an error floor. Our results show that the scheme based on the e2e SNR achieves the best performance and the one based on the EH the worst. The derived analytical framework provides useful insights on the design of such networks.
A microbial world within us

The microbial world within us includes a vast array of gastrointestinal (GI) tract communities that play an important role in health and disease. Significant progress has been made in recent years in describing the intestinal microbial composition based on the application of 16S ribosomal RNA (rRNA)‐based approaches. These were not only instrumental in providing a phylogenetic framework of the more than 1000 different intestinal species but also illustrated the temporal and spatial diversity of the microbial GI tract composition that is host‐specific and affected by the genotype. However, our knowledge of the molecular and cellular bases of host–microbe interactions in the GI tract is still very limited. Here an overview is presented of the most recent developments and applications of novel culture‐independent approaches that promise to unravel the mechanisms of GI tract functionality and subsequent possibilities to exploit specifically these mechanisms in order to improve gut health.