Miracle-dz/UniFAR-FTUs huggingface dataset:
Interpregnancy intervals and women’s knowledge of the ideal timing between birth and conception

Background Short interpregnancy intervals (IPIs) are associated with adverse obstetric outcomes. However, few studies have explored women’s understanding of ideal IPIs or investigated knowledge of the consequences of short IPIs. Methods We performed a prospective questionnaire-based study at two hospitals in Sydney, Australia. We recruited women attending antenatal clinics and collected demographic data, actual IPI, ideal IPI, contraceptive use, and education provided on birth-spacing and contraception following a previous live birth. We explored associations between an IPI <12 months and a selection of demographic and health variables. Results Data were collected from 467 women, of whom 344 were pregnant following a live birth. Overall, 72 (20.9%) women had an IPI <12 months only 7.5% of whom believed this was ideal, and the remaining stating their ideal IPI was over 12 months (52.3%) or they had no ideal IPI (40.3%). IPI <12 months following a live birth was significantly associated with younger age (p=0.043) but not with ethnicity, relationship status, education, religion, parity nor previous mode of delivery. IPI <12 months was associated with non-use of long-acting reversible contraception (LARC) (p<0.001), breastfeeding <12 months (p=0.041) and shorter ideal IPI (p=0.03). Less than half of the women (43.3%, n=149) reported having received advice about IPI and less than half about postnatal contraception (44.2%, n=147). Conclusions Younger age and non-use of LARC are significantly associated with IPIs <12 months. A minority of women with a short IPI perceived it to be ideal. Prevention of short IPIs could be achieved with improved access to postnatal contraception.
WNT1‐inducible signaling protein‐1 mediates TGF‐β1‐induced renal fibrosis in tubular epithelial cells and unilateral ureteral obstruction mouse models via autophagy

Renal fibrosis is a common pathway for the progression of all chronic kidney diseases to end‐stage kidney disease. Studies show that WNT1‐inducible signaling pathway protein‐1 (WISP‐1) is involved in the fibrosis of various organs. The aim of the study was to explore the functional role and potential mechanism of WISP‐1 in renal fibrosis. We observed that overexpression of WISP‐1 in rat tubular epithelial cells (TECs) enhanced transforming growth factor‐β1 (TGF‐β1)‐induced production of fibrotic markers, including collagen I (Col I), fibronectin (FN) and TGF‐β1, while inhibition of WISP‐1 suppressed such production. In vivo, the messenger RNA and protein levels of Col I, FN, and α‐smooth muscle actin were significantly inhibited after anti‐WISP‐1 antibody treatment for 7 days in unilateral ureteral obstruction mouse models. Moreover, blockade of WISP‐1 by anti‐WISP‐1 antibody significantly reduced autophagy‐related markers, including anti‐microtubule‐associated protein‐1 light chain 3 (LC3) and beclin 1, while increasing sequestosome 1. In addition, overexpression of WISP‐1 in TECs increased autophagy as evidenced by greater numbers of GFP‐LC3 puncta and increased expression of LC3 and beclin 1 in response to TGF‐β1. In contrast, knockdown of WISP‐1 by small interfering RNA decreased the number of GFP‐LC3 puncta and the expression of LC3 and beclin 1 in TGF‐β1‐treated TECs. Collectively, these data suggest that WISP‐1, as a profibrotic protein, may mediate renal fibrosis by inducing autophagy in both obstructive nephropathy and TGF‐β1‐treated TECs. WISP‐1 may serve as an effective therapeutic target for the treatment of renal fibrosis.
Some Aspects of CD8+ T-Cell Exhaustion Are Associated With Altered T-Cell Mitochondrial Features and ROS Content in HIV Infection.

BACKGROUND Reversing or preventing T-cell exhaustion is an important treatment goal in the context of HIV disease; however, the mechanisms that regulate HIV-specific CD8 T-cell exhaustion are incompletely understood. Since mitochondrial mass (MM), mitochondrial membrane potential (MMP), and cellular reactive oxygen species (ROS) content are altered in exhausted CD8 T cells in other settings, we hypothesized that similar lesions may arise in HIV infection. METHODS We sampled cryopreserved peripheral blood mononuclear cells from HIV-uninfected (n = 10) and HIV-infected participants with varying levels and mechanisms of viral control: viremic (VL > 2000 copies/mL; n = 8) or aviremic (VL < 40 copies/mL) due to antiretroviral therapy (n = 11) or natural control (n = 9). We characterized the MM, MMP, and ROS content of bulk CD8 T cells and MHC class I tetramer+ HIV-specific CD8 T cells by flow cytometry. RESULTS We observed higher MM, MMP, and ROS content across bulk effector-memory CD8 T-cell subsets in HIV-infected compared with HIV-uninfected participants. Among HIV-specific CD8 T cells, these features did not vary by the extent or mechanism of viral control but were significantly altered in cells displaying characteristics associated with exhaustion (eg, high PD-1 expression, low CD127 expression, and impaired proliferative capacity). CONCLUSIONS While we did not find that control of HIV replication in vivo correlates with the CD8 T-cell MM, MMP, or ROS content, we did find that some features of CD8 T-cell exhaustion are associated with alterations in mitochondrial state. Our findings support further studies to probe the relationship between mitochondrial dynamics and CD8 T-cell functionality in HIV infection.
Are Outcomes of Anterior Cervical Discectomy and Fusion Influenced by Presurgical Depression Symptoms on the Mental Component Score of the Short Form-12 Survey?

STUDY DESIGN Retrospective comparative study. OBJECTIVE The purpose of this study was to investigate whether preoperative depressive symptoms, measured by mental component score of the Short Form-12 survey (MCS-12), influences patient reported outcome measurements (PROMs) following an Anterior Cervical Discectomy and Fusion (ACDF) surgery for cervical degeneration. SUMMARY OF BACKGROUND DATA There is a paucity of literature regarding preoperative depression and PROMs following ACDF surgery for cervical degenerative disease. METHODS Patients who underwent an ACDF for degenerative cervical pathology were identified. A score of 45.6 on the MCS-12 was used as the threshold for depression symptoms, and patients were divided into two groups based on this value: depression (MCS-12 ≤ 45.6) and non-depression (MCS-12 > 45.6) groups. Outcomes including Neck Disability Index (NDI), physical component score of the Short Form-12 survey (PCS-12), and Visual Analogue Scale Neck (VAS Neck) and Arm (VAS Arm) pain scores were evaluated using independent sample t-test, recovery ratios, % of patients reaching the minimum clinically important difference (% MCID), and multiple linear regression - controlling for factors such as age, sex, and BMI. RESULTS The depression group was found to have significantly worse baseline pain and disability than the non-depression group in NDI (p < 0.001), VAS Neck pain (p < 0.001), and VAS Arm pain (p < 0.001) scores. Postoperatively, both groups improved to a similar amount with surgery based on the recovery ratio analysis. The depression group continued to have worse scores than the non-depression group in NDI (p = 0.010), PCS-12 (p = 0.026), and VAS Arm pain (p = 0.001) scores. Depression was not a significant predictor of change in any PROMs based on regression analysis. CONCLUSION Patients who presented with preoperative depression reported more pain and disability symptoms preoperatively and postoperatively, however both groups achieved similar degrees of improvement. LEVEL OF EVIDENCE 3.
Competitive Fitness of Mycobacterium tuberculosis in vitro

Background: While, bacteria resistance mutations can affect competitive fitness, given our multidrug-resistant (MDR) prevalence, we conducted this study to determine the impact of MDR on the competitive fitness of Mycobacterium tuberculosis (MTB) complex MDR strains. We conducted a cross-sectional study at the University Clinical Research Center (UCRC) from January to December 2017. New TB patients over aged of 18 were recruited at University teaching hospital and health reference centers of Bamako in USTTB Ethical committee approved protocols. Methods: MDR and drug-susceptible (wild-type [WT]) MTB strains (T1 and Beijing) and MTB H37Rv were competed on solid media in UCRC's Tuberculosis Laboratory. Competitive and individual cultures were incubated for 14 days at 37°C with 7% CO2. Number of generation, generation time, and relative competitive fitness (W) of the strains were calculated. Data were analyzed with Epi-Info 7.1. 5.2 software (CDC). P value was considered significant when it was <0.05. Scientific calculator (CS-82TL) was used for competitive fitness parameters calculations. Results: We performed 24 competitive cultures and 10 individual cultures. In individual cultures, strains' generation number was for Beijing (WT: 4.60 and mutant MR: 4.40), T1 (WT: 2.69 and MR: 2.37), and H37Rv: 2.91. Generation number of WT strains was less than those of MDR strains in both individual and competitive culture. Relative competitive fitness was below 1 (W<1) in 83.3%. Conclusion: MDR strains were less competitive than WT strains in 83.3% of cases. Resistant mutation impacts bacteria fitness.
Exogenous Interleukin-33 Contributes to Protective Immunity via Cytotoxic T-Cell Priming against Mucosal Influenza Viral Infection

Influenza is an infectious respiratory illness caused by the influenza virus. Though vaccines against influenza exist, they have limited efficacy. To additionally develop effective treatments, there is a need to study the mechanisms of host defenses from influenza viral infections. To date, the mechanism by which interleukin (IL)-33 modulates the antiviral immune response post-influenza infection is unclear. In this study, we demonstrate that exogenous IL-33 enhanced antiviral protection against influenza virus infection. Exogenous IL-33 induced the recruitment of dendritic cells, increased the secretion of pro-inflammatory cytokine IL-12, and promoted cytotoxic T-cell responses in the local microenvironment. Thus, our findings suggest a role of exogenous IL-33 in the antiviral immune response against influenza infection.
Monitoring of Low-Intensity Exposures via Luminescent Bioassays of Different Complexity: Cells, Enzyme Reactions, and Fluorescent Proteins

The current paper reviews the applications of luminescence bioassays for monitoring the results of low-intensity exposures which produce a stimulative effect. The impacts of radioactivity of different types (alpha, beta, and gamma) and bioactive compounds (humic substances and fullerenols) are under consideration. Bioassays based on luminous marine bacteria, their enzymes, and fluorescent coelenteramide-containing proteins were used to compare the results of the low-intensity exposures at the cellular, biochemical, and physicochemical levels, respectively. High rates of luminescence response can provide (1) a proper number of experimental results under comparable conditions and, therefore, proper statistical processing, with this being highly important for “noisy” low-intensity exposures; and (2) non-genetic, i.e., biochemical and physicochemical mechanisms of cellular response for short-term exposures. The results of cellular exposures were discussed in terms of the hormesis concept, which implies low-dose stimulation and high-dose inhibition of physiological functions. Dependencies of the luminescence response on the exposure time or intensity (radionuclide concentration/gamma radiation dose rate, concentration of the bioactive compounds) were analyzed and compared for bioassays of different organization levels.
Serum vitamin D concentrations are inversely related to prevalence of metabolic syndrome in Qatari women.

Hypovitaminosis D has reached epidemic proportions in Qatar. Vitamin D is linked to several cardiometabolic diseases such as metabolic syndrome (MetSyn), diabetes, and atherosclerosis. It is not known if vitamin D status is linked to cardiometabolic risk factors in Qatari women. Therefore, a relationship between serum 25-hydroxyvitmain D [25(OH)D] concentrations and MetSyn was investigated in Qatari women using the Qatar Biobank database. Study sample consisted of 700 women, aged 20-80 years old. A multivariate-adjusted logistic regression was used to determine relation between serum 25(OH)D and MetSyn prevalence. Multivariate linear regression was performed to determine the association between serum 25(OH)D and markers of MetSyn. Prevalences of MetSyn in the first (≈32%), second (≈27%), and third (≈28%) serum 25(OH)D quartiles were significantly higher compared to fourth serum 25(OH)D quartile (≈17.5%) (p < .035). The likelihood of having MetSyn was significantly higher in the first serum 25(OH)D quartile (OR, 1.92; 95% CI, 1.06, 3.49) compared to the fourth serum 25(OH)D quartile (p < .001) in multivariate-adjusted analysis. No relationship was observed between serum 25(OH)D and waist circumference, blood pressure, glycated hemoglobin (HbA1C), blood glucose, HDL-cholesterol, and serum triglycerides. This study showed an inverse relationship between prevalence of MetSyn and serum 25(OH)D in Qatari women. Given the widespread prevalence of vitamin D deficiency in Qatar, consideration should be given to vitamin D fortification of some selected staple foods and through targeted supplementation of vitamin D in those who are at risk for cardiometabolic diseases.
Phase 2 Study of Nilotinib in Pediatric Patients With Philadelphia Chromosome-Positive Chronic Myeloid Leukemia.

Chronic myeloid leukemia (CML) is rare in children and accounts for {less than or equal to} 15% of all myeloid leukemia cases. When we initiated this study with nilotinib, imatinib was the only tyrosine kinase inhibitor indicated for pediatric patients with Philadelphia chromosome-positive (Ph+) CML in chronic phase (CP); alternative treatment options were needed, particularly for patients who developed resistance/intolerance (R/I) to imatinib. This phase 2 study enrolled pediatric patients with either Ph+ CML-CP R/I to imatinib/dasatinib or newly diagnosed Ph+ CML-CP. Data presented are from analyses with up to 24 cycles' minimum follow-up (1 cycle = 28 days). Fifty-nine patients with Ph+ CML-CP were enrolled and 58 were treated (R/I, n = 33; newly diagnosed, n = 25). Major molecular response (MMR) rate at cycle 6 in the R/I cohort was 39.4% (primary endpoint); 57.6% and 81.8% of patients achieved or maintained MMR and complete cytogenetic response (CCyR), respectively, by 24 cycles. In patients with newly diagnosed disease, rates of MMR by cycle 12 and CCyR at cycle 12 were 64.0% each (primary endpoints); by cycle 24, cumulative MMR and CCyR rates were 68.0% and 84.0%, respectively. The safety profile of nilotinib in pediatric patients was generally comparable with the known safety profile in adults, although cardiovascular events were not observed in this study and hepatic laboratory abnormalities were more frequent; no new safety signals were identified. In summary, nilotinib demonstrated efficacy and a manageable safety profile in pediatric patients with Ph+ CML-CP. This trial was registered at ClinicalTrials.gov as #NCT01844765.
Direct in vivo electrochemical detection of resting dopamine using PEDOT/CNT functionalized microelectrodes.

Dopamine (DA) is a monoamine neurotransmitter responsible for the maintenance of a variety of vital life functions. In vivo DA signaling occurs over multiple time scales, from sub-second phasic release due to dopamine neuron firing, to tonic release responsible for long-term DA concentration changes over minutes to hours. Due to the complex, multifaceted nature of DA signaling, analytical sensing technology must be capable of recording DA from multiple locations and over multiple timescales. Decades of research has focused on improving in vivo detection capabilities for sub-second phasic DA, but the accurate detection of absolute resting DA levels in real time has proven challenging. We have developed a poly (3,4 ethylene dioxythiophene) (PEDOT)-based nanocomposite coating that exhibits excellent DA sensing capabilities for resting DA. PEDOT/functionalized carbon nanotube (PEDOT/CNT) coated carbon fiber microelectrodes (CFEs) are capable of directly measuring resting DA using square wave voltammetry (SWV) with high sensitivity and selectivity. Incorporation of a PEDOT/CNT coating significantly increases the sensitivity for the detection of resting DA by a factor of 422. SWV measurements performed at PEDOT/CNT functionalized CFEs implanted in the rat dorsal striatum reveal the absolute basal DA concentration to be 82 ± 6 nM . Systemic administration of the dopamine transporter inhibitor, nomifensine increases resting DA to a maximum 207 ± 16 nM at 28 ± 2 minutes following injection. PEDOT/CNT was also functionalized onto individual gold electrode sites along silicon microelectrode arrays (MEAs) to produce a multisite DA sensing electrode. MEA implantation allows for the quantification of basal DA from different brain regions with excellent spatial resolution. SWV detection paired with PEDOT/CNT functionalized is highly adaptable and shows great promise for tonic DA detection with high spatial and temporal resolution.
Risk factors for further sick leave among Japanese workers returning to work after an episode of major depressive disorder: a prospective follow-up study over 1 year

Objectives We aimed to investigate the risk factors for further sick leave episodes among Japanese workers returning to work after time off with a major depressive disorder. Design A prospective study with 1 year of follow-up. Participants We recruited 103 workers who had returned to work after taking sick leave with a major depressive disorder. Adjusted HRs with 95% CIs were calculated using Cox proportional hazard models to examine the risk of further sick leave. Results In the adjusted analysis, we show that Social Adaptation Self-evaluation Scale scores (HR 0.95; p=0.019), 3-back correct response rate (N-back test) (HR 0.97; p<0.001) and benzodiazepine dosage (diazepam equivalent) (HR1.07; p=0.014) were associated with further episodes of sick leave. Conclusions Poorer social and cognitive functioning, together with higher diazepam dosages, were associated with an increased likelihood of additional sick leave.
Drivers of the dive response in trained harbour porpoises (Phocoena phocoena)

ABSTRACT Pronounced dive responses through peripheral vasoconstriction and bradycardia enable prolonged apnoea in marine mammals. For most vertebrates, the dive response is initiated upon face immersion, but little is known about the physical drivers of diving and surfacing heart rate in cetaceans whose faces are always mostly submerged. Using two trained harbour porpoises instrumented with an ECG-measuring sound-and-movement tag (DTAG-3), we investigated the initiation and progression of bradycardia and tachycardia during apnoea and eupnoea for varying levels of immersion. We show that paranasal wetting drives bradycardia initiation and progression, whereas apnoea leads to dive-level bradycardia eventually, but not instantly. At the end of dives, heart rate accelerates independently of lung expansion, perhaps in anticipation of surfacing; however, full tachycardia is only engaged upon inhalation. We conclude that breathing drives surface tachycardia, whereas blowhole wetting is an important driver of bradycardia; however, anticipatory/volitional modulation can overrule such responses to sensory inputs. Summary: Harbour porpoise diving bradycardia is initiated with blowhole submergence rather than apnoea alone, while surface tachycardia is only fully obtained with lung ventilation, yet initiated anticipatorily.
Atrial Fibrillation Ablation and Reduction of Stroke Events: Understanding the Paradoxical Lack of Evidence.

Atrial fibrillation (AF) is the most prevalent chronic arrhythmia and a major cause of stroke and mortality. It is thought to confer an overall 5-fold increased risk of a cerebrovascular event, causing ≈one-third of all ischemic strokes. Half of the 2 to 3 fold higher risk of mortality among AF patients is related to AF itself, not only via fatal progression of heart failure, the most frequent mode, but also sudden death and embolic events. Importantly, AF patients who suffer a cardioembolic stroke have a worse outcome compared with stroke patients without AF. Anticoagulation has been shown to reduce the risk of a cerebrovascular event in AF patients. However, despite adequate anticoagulation, some patients remain at risk of stroke. Whether successful catheter ablation can reduce this risk remains unclear. Although there has not been any convincing evidence thus far that AF ablation leads to a reduction in the risk of stroke, no randomized study was powered to address this question. In this review article, we discuss the AF-stroke association, as well as the apparent lack of evidence supporting the use of ablation for the specific reduction of this end point.
Rapamycin blocks the neuroprotective effects of sex steroids in the adult birdsong system

In adult songbirds, the telencephalic song nucleus HVC and its efferent target RA undergo pronounced seasonal changes in morphology. In breeding birds, there are increases in HVC volume and total neuron number, and RA neuronal soma area compared to nonbreeding birds. At the end of breeding, HVC neurons die through caspase‐dependent apoptosis and thus, RA neuron size decreases. Changes in HVC and RA are driven by seasonal changes in circulating testosterone (T) levels. Infusing T, or its metabolites 5α‐dihydrotestosterone (DHT) and 17 β‐estradiol (E2), intracerebrally into HVC (but not RA) protects HVC neurons from death, and RA neuron size, in nonbreeding birds. The phosphoinositide 3‐kinase (PI3K)‐Akt (a serine/threonine kinase)‐mechanistic target of rapamycin (mTOR) signaling pathway is a point of convergence for neuroprotective effects of sex steroids and other trophic factors. We asked if mTOR activation is necessary for the protective effect of hormones in HVC and RA of adult male Gambel's white‐crowned sparrows (Zonotrichia leucophrys gambelii). We transferred sparrows from breeding to nonbreeding hormonal and photoperiod conditions to induce regression of HVC neurons by cell death and decrease of RA neuron size. We infused either DHT + E2, DHT + E2 plus the mTOR inhibitor rapamycin, or vehicle alone in HVC. Infusion of DHT + E2 protected both HVC and RA neurons. Coinfusion of rapamycin with DHT + E2, however, blocked the protective effect of hormones on HVC volume and neuron number, and RA neuron size. These results suggest that activation of mTOR is an essential downstream step in the neuroprotective cascade initiated by sex steroid hormones in the forebrain.
Evaluation of oncologic outcomes in head and neck cancer patients ≥80 years old based on adherence to NCCN guideline for postoperative adjuvant treatment

There is a paucity of literature characterizing outcomes in older adult patients with head and neck cancer (HNC). This study aims to describe patients from this group, their adherence to National Comprehensive Cancer Network (NCCN) adjuvant treatment guidelines, and the impact of guideline adherence on overall survival (OS).