Miracle-dz/UniFAR-FTUs huggingface dataset:
A priori choice of neuraxial labour analgesia and breastfeeding initiation success: a community-based cohort study in an Italian baby-friendly hospital

Objective To investigate whether the nature of the decision about receiving neuraxial labour analgesia is associated with breastfeeding initiation success (BIS), defined as exclusive breastfeeding until discharge associated with postnatal weight loss <7% at 60 hours from birth. Design Single-centre community-based cohort study. Setting An Italian baby-friendly hospital, from 1 July 2011 to 22 September 2015. Participants Inclusion criteria: women vaginally delivering singleton cephalic newborns and willing to breastfeed. Exclusion criteria: women who delivered in uterus-dead fetuses, were single or requested but did not receive neuraxial analgesia. Overall, 775 out of the 3628 enrolled women received neuraxial analgesia. Results Compared with women who tried to cope with labour pain, those who decided a priori to receive neuraxial analgesia had less BIS (planned vaginal birth: 2121/3421 (62.0%), vs 102/207 (49.3%; p<0.001; risk difference (RD), 12.7%); actual vaginal birth: 1924/2994 (64.3%), vs 93/189 (49.2%; p<0.001; RD, 15.1%)). Multivariable analyses with antelabour-only confounders confirmed both associations (planned vaginal birth: relative risk (RR), 0.65; 95% CI, 0.48 to 0.87; actual vaginal birth: RR, 0.59; 95% CI, 0.43 to 0.80). Although women who requested analgesia as a last resort had less BIS than did those successfully coping with labour pain in the bivariable analyses (planned vaginal birth: 1804/2853 (63.2%), vs 317/568 (55.8%; p=0.001; RD, 7.4%); actual vaginal birth: 1665/2546 (65.4%), vs 259/448 (57.8%; p=0.002; RD, 7.6%)), multivariable analyses with either antelabour-only or peripartum confounders did not confirm these associations (planned vaginal birth: RR, 0.99; 95% CI, 0.80 to 1.23; actual vaginal birth: RR, 0.90; 95% CI, 0.69 to 1.16). Conclusions Compared with trying to cope with labour pain, a priori choice of neuraxial analgesia is negatively associated with BIS. Conversely, compared with having successfully coped with pain, requesting neuraxial analgesia as a last resort is not negatively associated with BIS.
MicroRNA-127 inhibits cell proliferation via targeting Kif3b in pancreatic β cells

MicroRNAs (miRNAs) have been implicated in β cells dysfunction. Previous studies indicated that miR-127 was specifically abundant in β cells and one of its target genes, Kif3b, promoted cell proliferation. However, the impact of the miR-127-Kif3b axis on β cells remains unknown. In this study, we revealed that miR-127 level was declined both in islets from the mice with a high-fat diet and in MIN6 cells with elevated glucose treatment. The elevated level of miR-127 attenuated β cell proliferation by repressing Kif3b expression without affecting apoptosis and cell cycle, and it dampened insulin secretion. Moreover, β cell-derived miR-127 could also affect the islet endothelial cell-line, MS1, in vitro via the transfer of extracellular vesicles (EVs). Treating MS1 cells with the EVs secreted by MIN6 cells exhibited a higher ability in cell migration and tube formation. However, this effect was abolished by the miR-127 inhibitor co-cultured with EVs-treated MS1 cells. Thus, we define that miR-127 is a crucial regulator of insulin secretion and cell proliferation in pancreatic β cells as well as a potential functional regulation factor in islet endothelial cells.
Individual Differences in Maternal, Marital, Parenting and Child Outcomes Following Perinatal Loss: A Longitudinal Study

ABSTRACT Objective: To examine the impact of past perinatal loss on mothers and children in a community sample and to consider maternal race and adult attachment status as moderators. Background: Prior perinatal loss has been shown to impact subsequent maternal parenting and child outcomes, but findings have been inconsistent particularly in minority mothers and samples not chosen due to perinatal loss history. Methods: Participants were 204 first-time mothers from a longitudinal study about predictors of sensitivity. Mothers completed the Adult Attachment Interview prenatally and reported on depressive symptoms and marital satisfaction prenatally and at 6 months and 1 year postpartum. Maternal sensitivity was observed at 6 months and 1 year, and infant-mother attachment security was assessed via the Strange Situation when children were 1 year old. Mothers reported on their reproductive history and current attitudes about the target child during the preschool period. Results: Fifty-eight (28.43%) mothers had a history of prior perinatal loss. Between group analysis revealed no differences based on perinatal loss and no moderation by maternal race or adult attachment. However, within the loss group, mothers who experienced losses later in the gestational period had less positive feelings about parenting and their children had less secure attachments to them; and mothers who had more perinatal losses had higher depressive symptoms at 1 year postpartum and less positive attitudes about parenting independent of race and SES. Conclusion: In the circumstance of multiple and later perinatal losses maternal well-being and child outcomes may be negatively impacted.
Multiplexed Immunohistochemistry for Molecular and Immune Profiling in Lung Cancer—Just About Ready for Prime-Time?

As targeted molecular therapies and immuno-oncology have become pivotal in the management of patients with lung cancer, the essential requirement for high throughput analyses and clinical validation of biomarkers has become even more intense, with response rates maintained in the 20%–30% range. Moreover, the list of treatment alternatives, including combination therapies, is rapidly evolving. The molecular profiling and specific tumor-associated immune contexture may be predictive of response or resistance to these therapeutic strategies. Multiplexed immunohistochemistry is an effective and proficient approach to simultaneously identify specific proteins or molecular abnormalities, to determine the spatial distribution and activation state of immune cells, as well as the presence of immunoactive molecular expression. This method is highly advantageous for investigating immune evasion mechanisms and discovering potential biomarkers to assess mechanisms of action and to predict response to a given treatment. This review provides views on the current technological status and evidence for clinical applications of multiplexing and how it could be applied to optimize clinical management of patients with lung cancer.
Structural basis for RNA translocation by DEAH-box ATPases

Abstract DEAH-box adenosine triphosphatases (ATPases) play a crucial role in the spliceosome-mediated excision of pre-mRNA introns. Recent spliceosomal cryo-EM structures suggest that these proteins utilize translocation to apply forces on ssRNAs rather than direct RNA duplex unwinding to ensure global rearrangements. By solving the crystal structure of Prp22 in different adenosine nucleotide-free states, we identified two missing conformational snapshots of genuine DEAH-box ATPases that help to unravel the molecular mechanism of translocation for this protein family. The intrinsic mobility of the RecA2 domain in the absence of adenosine di- or triphosphate (ADP/ATP) and RNA enables DEAH-box ATPases to adopt different open conformations of the helicase core. The presence of RNA suppresses this mobility and stabilizes one defined open conformation when no adenosine nucleotide is bound. A comparison of this novel conformation with the ATP-bound state of Prp43 reveals that these ATPases cycle between closed and open conformations of the helicase core, which accommodate either a four- or five-nucleotide stack in the RNA-binding tunnel, respectively. The continuous repetition of these states enables these proteins to translocate in 3′-5′ direction along an ssRNA with a step-size of one RNA nucleotide per hydrolyzed ATP. This ATP-driven motor function is maintained by a serine in the conserved motif V that senses the catalytic state and accordingly positions the RecA2 domain.
A Lysine Residue Essential for Geminivirus Replication Also Controls Nuclear Localization of the Tomato Yellow Leaf Curl Virus Rep Protein

Nuclear activity of the replication initiator protein (Rep) of geminiviruses is essential for viral replication. We now define that one highly conserved lysine is important for nuclear import of Rep from three different begomoviruses. To our knowledge, this is the first time that nuclear localization has been mapped for any geminiviral Rep protein. Our data add another key function to this lysine residue, besides its roles in viral DNA replication and interaction with host factors, such as the SUMO E2-conjugating enzyme. ABSTRACT Geminiviruses are single-stranded DNA (ssDNA) viruses that infect a wide range of plants. To promote viral replication, geminiviruses manipulate the host cell cycle. The viral protein Rep is essential to reprogram the cell cycle and then initiate viral DNA replication by interacting with a plethora of nuclear host factors. Even though many protein domains of Rep have been characterized, little is known about its nuclear targeting. Here, we show that one conserved lysine in the N-terminal part of Rep is pivotal for nuclear localization of the Rep protein from Tomato yellow leaf curl virus (TYLCV), with two other lysines also contributing to its nuclear import. Previous work had identified that these residues are essential for Rep from Tomato golden mosaic virus (TGMV) to interact with the E2 SUMO-conjugating enzyme (SCE1). We here show that mutating these lysines leads to nuclear exclusion of TYLCV Rep without compromising its interaction with SCE1. Moreover, the ability of TYLCV Rep to promote viral DNA replication also depends on this highly conserved lysine independently of its role in nuclear import of Rep. Our data thus reveal that this lysine potentially has a broad role in geminivirus replication, but its role in nuclear import and SCE1 binding differs depending on the Rep protein examined. IMPORTANCE Nuclear activity of the replication initiator protein (Rep) of geminiviruses is essential for viral replication. We now define that one highly conserved lysine is important for nuclear import of Rep from three different begomoviruses. To our knowledge, this is the first time that nuclear localization has been mapped for any geminiviral Rep protein. Our data add another key function to this lysine residue, besides its roles in viral DNA replication and interaction with host factors, such as the SUMO E2-conjugating enzyme.
Higher diet quality in university students is associated with higher academic achievement: a cross‐sectional study

BACKGROUND Unhealthy diets are typical of university students and the effects may be wider reaching than health. The present study aimed to describe the association between dietary intake and academic achievement in a sample of Australian university students. METHODS A cross-sectional analysis of data from an online survey of 278 students from the University of Newcastle (UON), Australia [mean (SD) age 26.9 (10.5) years; 70.9% female] was conducted. Dietary intake, in terms of diet quality score [Australian Recommended Food Score (ARFS)], including individual sub-scales, and percentage energy per day from energy-dense nutrient poor (EDNP) foods, including individual sub-groups, was assessed using the validated Australian Eating Survey Food Frequency Questionnaire, and academic achievement was assessed as self-reported grade point average (GPA). The association between GPA and dietary intake was explored using linear regression, with adjustment for socio-demographic and student characteristics. RESULTS Higher GPA was associated with higher diet quality (ARFS) (β = 0.02, P = 0.011), higher sub-scale scores for vegetables (β = 0.03, P = 0.026) and fruit (β = 0.05, P = 0.029) and with lower percentage energy per day from EDNP foods overall (β = -0.01, P = 0.047) and also from sweetened drinks (β = -0.06, P < 0.001). CONCLUSIONS The results of the present study demonstrate small associations between a healthier dietary intake and higher academic achievement, as well as vice versa. Given that the associations were small, they may not be particularly meaningful. However, this evidence could be used as a motivator for efforts aiming to improve dietary intake among university students.
[Risk Factors of Medical Device-Related Pressure Ulcer in Intensive Care Units].

PURPOSE The purpose of this study was to identify the characteristics of and risk factors for medical-device-related pressure ulcer (MDRPU) development in intensive care units. METHODS A prospective cohort study design was used, and the participants were 253 adult patients who had stayed in medical and surgical intensive care units. Data were collected regarding the application of medical devices and MDRPU-related characteristics over a period of six months from June to November, 2017. Data were analyzed using independent t-test, χ²-test, Fisher's exact test, and binary logistic regression analysis with the SPSS 21.0 program. RESULTS Among the 253 participants, MDRPUs occurred in 51 (19.8%) participants. The results of the logistic regression analysis showed that the risk factors for MDRPUs were the use of endotracheal tubes (OR=5.79, 95% CI: 1.66~20.20), having had surgery (OR=2.95, 95% CI: 1.11~7.77), being in a semi-coma/coma (OR=5.79, 95% CI: 1.04~32.05), and sedation (OR=5.54, 95% CI: 1.39~22.19). CONCLUSION On the basis of the study results, it is effectively facilitated by nurses when they care for patients with MDRPUs in intensive care units and the results are expected to be of help in preventive education for MDRPU development as well as preparing the base data for intervention studies.
Hormone replacement therapy attenuates hearing loss: Mechanisms involving estrogen and the IGF‐1 pathway

Estradiol (E) is a multitasking hormone that plays a prominent role in the reproductive system, and also contributes to physiological and growth mechanisms throughout the body. Frisina and colleagues have previously demonstrated the beneficial effects of this hormone, with E‐treated subjects maintaining low auditory brainstem response (ABR) thresholds relative to control subjects (Proceedings of the National Academy of Sciences of the United States of America, 2006;103:14246; Hearing Research, 2009;252:29). In the present study, we evaluated the functionality of the peripheral and central auditory systems in female CBA/CaJ middle‐aged mice during and after long‐term hormone replacement therapy (HRT) via electrophysiological and molecular techniques. Surprisingly, there are very few investigations about the side effects of HRT in the auditory system after it has been discontinued. Our results show that the long‐term effects of HRT are permanent on ABR thresholds and ABR gap‐in‐noise (GIN) amplitude levels. E‐treated animals had lower thresholds and higher amplitude values compared to other hormone treatment subject groups. Interestingly, progesterone (P)‐treated animals had ABR thresholds that increased but amplitude levels that remained relatively the same throughout treatment. These results were consistent with qPCR experiments that displayed high levels of IGF‐1R in the stria vascularis (SV) of both E and P animal groups compared to combination treatment (E + P) animals. IGF‐1R plays a vital role in mediating anti‐apoptotic responses via the PI3K/AKT pathway. Overall, our findings gain insights into the neuro‐protective properties of E hormone treatments as well as expand the scientific knowledge base to help women decide whether HRT is the right choice for them.
Motor Recovery after Transplantation of Bone Marrow Mesenchymal Stem Cells in Rat Models of Spinal Cord Injury

Background: Neuronal tissue has a limited potential to self-renew or get repaired after damage. Cell therapies using stem cells are promising approaches for the treatment of central nervous system (CNS) injuries. However, the clinical use of embryonic stem cells is limited by ethical concerns and other scientific consequences. Bone marrow mesenchymal stromal cells (BM-MSC) could represent an alternative source of stem cells for replacement therapy. Indeed, many studies have demonstrated that MSCs can give rise to neuronal cells as well as many tissue-specific cell phenotypes. Purpose: Motor recovery by transplantation of bone marrow MSCs in rat models of spinal cord injury (SCI). Methods: Bone marrow was collected from the femur of albino Wistar rats. MSCs were separated using the Ficoll-Paque density gradient method and cultured in Dulbecco’s Modified Eagle Medium supplemented with 20% fetal bovine serum. Cultured MSC was characterized by immunohistochemistry and flow cytometry and neuronal-induced cells were further characterized for neural markers. Cultured MSCs were transplanted into the experimentally injured spinal cord of Wistar rats. Control (injured, but without cell transplantation) and transplanted rats were followed up to 8 weeks, analyzed using the Basso, Beattie, Bresnahan (BBB) scale and electromyography (EMG) for behavioral and physiological status of the injured spinal cord. Finally, the tissue was evaluated histologically. Results: Rat MSCs expressed positivity for a panel of MSC markers CD29, CD54, CD90, CD73, and CD105, and negativity for hematopoietic markers CD34, CD14, and CD45. In vitro neuronal transdifferentiated MSCs express positivity for β III tubulin, MAP2, NF, NeuN, Nav1.1, oligodendrocyte (O4), and negativity for glial fibrillary acid protein. All the treated groups show promising hind-limb motor recovery BBB score, except the control group. There was increased EMG amplitude in treated groups as compared to the control group. Green fluorescent protein (GFP)-labeled MSC survived and differentiated into neurons in the injured spinal cord, which is responsible for functional recovery. Conclusion: Our results demonstrate that BM-MSC has the potential to repair the injured cord in rat models of SCI. Thus, BM-MSC appears to be a promising candidate for cell-based therapy in CNS injury.
BRD4 inhibition attenuates inflammatory response in microglia and facilitates recovery after spinal cord injury in rats

The pathophysiology of spinal cord injury (SCI) involves primary injury and secondary injury. For the irreversibility of primary injury, therapies of SCI mainly focus on secondary injury, whereas inflammation is considered to be a major target for secondary injury; however the regulation of inflammation in SCI is unclear and targeted therapies are still lacking. In this study, we found that the expression of BRD4 was correlated with pro‐inflammatory cytokines after SCI in rats; in vitro study in microglia showed that BRD4 inhibition either by lentivirus or JQ1 may both suppress the MAPK and NF‐κB signalling pathways, which are the two major signalling pathways involved in inflammatory response in microglia. BRD4 inhibition by JQ1 not only blocked microglial M1 polarization, but also repressed the level of pro‐inflammatory cytokines in microglia in vitro and in vivo. Furthermore, BRD4 inhibition by JQ1 can improve functional recovery and structural disorder as well as reduce neuron loss in SCI rats. Overall, this study illustrates that microglial BRD4 level is increased after SCI and BRD4 inhibition is able to suppress M1 polarization and pro‐inflammatory cytokine production in microglia which ultimately promotes functional recovery after SCI.
Pregnancy outcomes of elective induction in low-risk term pregnancies

Abstract We investigated the mode of delivery and perinatal outcomes in low-risk pregnant women whose labor was electively induced or expectantly managed at term. Healthy women with viable, vertex singleton pregnancies at 37+0 to 40+6 weeks of gestation were included. Women electively induced (n = 416) in each week (37+0–37+6, 38+0–38+6, 39+0–39+6, 40+0–40+6 weeks) were compared with pregnant women with spontaneous labor (n = 487). The primary outcome was mode of delivery. A propensity score (PS) was derived using logistic regression to model the probability of elective induction group as a function of potential confounders. Altogether, 284 women with elective induction were matched with 284 women who underwent expectant management to create a PS-matched population. All analysis was performed using SAS software, version 9.4 (SAS Institute Inc., Cary, NC). All P values reported of the significance level was set at <. 05. There are no significant differences of delivery mode, neonatal intensive care unit (NICU) admission, and neonatal complication between PS-matched groups. Incidence of antepartum complications showed higher in the elective induction group compared to the spontaneous labor group (P = .04). When comparing each gestational week, incidence of NICU admission at 38 weeks in the elective induction group [10/74 (13.5%)] was significantly higher than in and the spontaneous labor group [2/74 (2.7%)] (P = .04). Elective induction of labor at term is not associated with increased risk of cesarean delivery. However, overall incidence of NICU admission at 38 gestational weeks seems to be increased in elective induction.
Attenuation of weight loss through improved antilipolytic effect in adipose tissue via the SGLT2 inhibitor tofogliflozin.

CONTEXT Although calorie loss from increased urinary glucose excretion continues after long-term treatment with SGLT2 inhibitors, the mechanisms of the attenuated weight loss due to SGLT2 inhibitors are not well known. OBJECTIVE To examine the mechanism of the attenuated weight loss during long-term treatment with an SGLT2 inhibitor, tofogliflozin, focussing on the antilipolytic effect of insulin on adipose tissue. DESIGN AND PARTICIPANTS An integrated analysis was performed using data from two Phase 3 studies of 52 weeks of tofogliflozin administration. The antilipolytic effect was evaluated using adipose tissue insulin resistance (Adipo-IR) calculated from the product of fasting insulin (f-IRI) and fasting free fatty acids (f-FFA). RESULTS Analysed were 774 patients with type 2 diabetes (mean age 58.5 years; HbA1c 8.1%; BMI 25.6 kg/m2; eGFR 83.9 mL/min/1.73m2; 66% men). Weight loss plateaued between Weeks 24 and 52 after decreasing significantly. f-IRI decreased significantly from baseline to Week 24, and the decrease was maintained until Week 52. f-FFA significantly increased, peaked at Week 24, then declined from Weeks 24 to 52. Adipo-IR declined progressively throughout the 52 weeks (-3.6 and -6.2 mmol/L·pmol/L at Weeks 24 and 52, respectively, (p<0.001) vs. baseline). Higher baseline Adipo-IR levels were independently associated with greater weight loss at Week 52. CONCLUSIONS The improved antilipolytic effect in adipose tissue may attenuate progressive lipolysis leading to attenuating future weight loss induced by an SGLT2 inhibitor in patients with type 2 diabetes.