Miracle-dz/UniFAR-FTUs huggingface dataset:
Bleeding complications and antithrombotic treatment in 264 pregnancies in antiphospholipid syndrome

Purpose The purpose of this study was to evaluate the safety of antithrombotic treatments prescribed during pregnancy in patients with antiphospholipid syndrome (APS). Methods This international, multicenter study included two cohorts of patients: a retrospective French cohort and a prospective US cohort (PROMISSE study). Inclusion criteria were (1) APS (Sydney criteria), (2) live pregnancy at 12 weeks of gestation (WG) with (3) follow-up data until six weeks post-partum. According to APS standard of care, patients were treated with aspirin and/or low-molecular weight heparin (LMWH) at prophylactic (pure obstetric APS) or therapeutic doses (history of thrombosis). Major bleeding was defined as abnormal blood loss during the pregnancy and/or post-partum period requiring intervention for hemostasis or transfusion, or during the peripartum period greater than 500 mL and/or requiring surgery or transfusion. Other bleeding events were classified as minor. Results Two hundred and sixty-four pregnancies (87 prospectively collected) in 204 patients were included (46% with history of thrombosis, 23% with associated systemic lupus). During pregnancy, treatment included LMWH (n = 253; 96%) or low-dose aspirin (n = 223; 84%), and 215 (81%) patients received both therapies. The live birth rate was 89% and 82% in the retrospective and prospective cohorts, respectively. Adverse pregnancy outcomes occurred in 28% of the retrospective cohort and in 40% of the prospective cohort. No maternal death was observed in either cohort. A combined total of 45 hemorrhagic events (25%) occurred in the retrospective cohort, but major bleeding was reported in only six pregnancies (3%). Neither heparin nor aspirin alone nor combined therapy increased the risk of hemorrhage. We also did not observe an increased rate of bleeding in the case of a short interval between last LMWH (less than 24 hours) or aspirin (less than five days) doses and delivery. Only emergency Caesarean section was significantly associated with an increased risk of bleeding (odds ratio (OR) 5.03 (1.41–17.96); p=. 016). In the prospective cohort, only one minor bleeding event was reported (vaginal bleeding). Conclusion Our findings support the safety of antithrombotic therapy with aspirin and/or LMWH during pregnancy in high-risk women with APS, and highlight the need for better treatments to improve pregnancy outcomes in APS. PROMISSE Study ClinicalTrials.gov identifier: NCT00198068.
Factors associated with additional anterior cruciate ligament reconstruction and register comparison: a systematic review on the Scandinavian knee ligament registers

Objective To present an overview of the Scandinavian knee ligament registers with regard to factors associated with additional ACL reconstruction, and studies comparing the Scandinavian registers with other knee ligament registers. Design Systematic review. Data sources Four electronic databases: PubMed, EMBASE, the Cochrane Library and AMED were searched, and 157 studies were identified. Two reviewers independently screened titles, abstracts and full-text studies for eligibility. A modified version of the Downs and Black checklist was applied for quality appraisal. Eligibility criteria for selecting studies Eligible studies were those published since the establishment of the Scandinavian registers in 2004, which reported factors associated with additional ACL reconstruction and compared data from other registers. Results Thirty-one studies met the inclusion criteria and generally displayed good reporting quality. Adolescent age (<20 years) was the most common factor associated with additional ACL reconstruction. The choice of hamstring tendon graft compared with patella tendon, transportal femoral tunnel drilling, smaller graft diameter and utilisation of suspensory fixation devices were associated with additional ACL reconstruction. Concomitant cartilage injury decreased the likelihood of additional ACL reconstruction. Patient sex alone did not influence the likelihood. The demographics of patients undergoing ACL reconstruction in the Scandinavian registers are comparable to registers in other geographical settings. However, there are differences in surgical factors including the presence of intra-articular pathology and graft choice. Summary The studies published from the Scandinavian registers in general have a high reporting quality when regarded as cohort studies. Several factors are associated with undergoing additional ACL reconstruction. The results from the registers may help facilitate treatment decisions.
On the design and efficacy assessment of self‐assembling peptide‐based hydrogel‐glycosaminoglycan mixtures for potential repair of early stage cartilage degeneration

Peptide‐based hydrogels are of interest for their potential use in regenerative medicine. Combining these hydrogels with materials that may enhance their physical and biological properties, such as glycosaminoglycans, has the potential to extend their range of biomedical applications, for example in the repair of early cartilage degeneration. The aim of this study was to combine three self‐assembling peptides (P11‐4, P11‐8, and P11‐12) with chondroitin sulphate at two molar ratios of 1:16 and 1:64 in 130 and 230 mM Na+ salt concentrations. The study investigates the effects of mixing self‐assembling peptide and glycosaminoglycan on the physical and mechanical properties at 37°C. Peptide alone, chondroitin sulphate alone, and peptide in combination with chondroitin sulphate were analysed using Fourier transform infrared spectroscopy to determine the β‐sheet percentage, transmission electron microscopy to determine the fibril morphology, and rheology to determine the elastic and viscous modulus of the materials. All of the variables (peptide, salt concentration, and chondroitin sulphate molar ratio) had an effect on the mechanical properties, β‐sheet formation, and fibril morphology of the hydrogels. P11‐4 and P11‐8‐chondroitin sulphate mixtures, at both molar ratios, were shown to have a high β‐sheet percentage, dense entangled fibrillar networks, as well as high mechanical stiffness in both (130 and 230 mM) Na+ salt solutions when compared with the P11‐12/chondroitin sulphate mixtures. These peptide/chondroitin sulphate hydrogels show promise for biomedical applications in glycosaminoglycan depleted tissues.
Are Efficient Deep Representations Learnable?

Many theories of deep learning have shown that a deep network can require dramatically fewer resources to represent a given function compared to a shallow network. But a question remains: can these efficient representations be learned using current deep learning techniques? In this work, we test whether standard deep learning methods can in fact find the efficient representations posited by several theories of deep representation. Specifically, we train deep neural networks to learn two simple functions with known efficient solutions: the parity function and the fast Fourier transform. We find that using gradient-based optimization, a deep network does not learn the parity function, unless initialized very close to a hand-coded exact solution. We also find that a deep linear neural network does not learn the fast Fourier transform, even in the best-case scenario of infinite training data, unless the weights are initialized very close to the exact hand-coded solution. Our results suggest that not every element of the class of compositional functions can be learned efficiently by a deep network, and further restrictions are necessary to understand what functions are both efficiently representable and learnable.
From random to regular: neural constraints on the emergence of isochronous rhythm during cultural transmission

Abstract A core design feature of human communication systems and expressive behaviours is their temporal organization. The cultural evolutionary origins of this feature remain unclear. Here, we test the hypothesis that regularities in the temporal organization of signalling sequences arise in the course of cultural transmission as adaptations to aspects of cortical function. We conducted two experiments on the transmission of rhythms associated with affective meanings, focusing on one of the most widespread forms of regularity in language and music: isochronicity. In the first experiment, we investigated how isochronous rhythmic regularities emerge and change in multigenerational signalling games, where the receiver (learner) in a game becomes the sender (transmitter) in the next game. We show that signalling sequences tend to become rhythmically more isochronous as they are transmitted across generations. In the second experiment, we combined electroencephalography (EEG) and two‐player signalling games over 2 successive days. We show that rhythmic regularization of sequences can be predicted based on the latencies of the mismatch negativity response in a temporal oddball paradigm. These results suggest that forms of isochronicity in communication systems originate in neural constraints on information processing, which may be expressed and amplified in the course of cultural transmission.
Respiratory Health Outcomes, Rhinitis, and Eczema in Workers from Grain Storage Facilities in Costa Rica

Objectives To examine the associations of inhalable grain dust exposure with respiratory health outcomes, rhinitis, and eczema reported by workers from rice, wheat, and maize storage facilities. Methods A cross-sectional study of 136 workers (73 operators and 63 administrative staff and other workers) from eight Costa Rican grain storage facilities was conducted in 2014-2015. Full-shift personal inhalable dust samples from all workers were collected. Study participants were administered a short version of the European Community Respiratory Health Survey questionnaire to identify symptoms of asthma, chronic bronchitis, rhinitis, and eczema. Associations between grain dust exposure and health outcomes were assessed using multivariable logistic and negative binomial regression models adjusted for age, smoking history, grain type, and presence of pets or farm animals in the home. Results The median inhalable grain dust concentration was 2.0 (25th to 75th percentile: 0.3-7.0) mg m-3. Higher concentrations of inhalable dust were associated with increased odds of (i) asthma symptoms or medication use [adjusted Odds ratio (ORa) per 10-fold increase in dust concentration 2.7; 95% confidence interval (CI): 1.3-6.7]; (ii) a score of at least two out of five symptoms suggestive of asthma (ORa 1.2; 95% CI: 1.0-1.3); and (iii) eczema (ORa 3.6; 95% CI: 1.7-9.6). No associations of inhalable grain dust exposure with chronic bronchitis and rhinitis were observed. Conclusions High exposure to inhalable dust in Costa Rican grain storage facilities was associated to asthma symptoms and eczema in workers.
Synthetic lethality of TNK2 inhibition in PTPN11-mutant leukemia

Dasatinib or TNK2-specific inhibitors may treat PTPN11-mutant leukemia. A ready-to-go treatment for AML and JMML In some acute myeloid and juvenile myelomonocytic leukemias (AML and JMML, respectively), tumor growth is driven by activating mutations in the phosphatase PTPN11. Jenkins et al. found that mutant PTPN11 activity is enhanced by the kinase TNK2. The multikinase inhibitor dasatinib decreased the activity of TNK2, mutant PTPN11, and downstream proliferative pathways in patient cells in culture; decreased their growth in murine bone marrow cocultures; and extended survival in a patient with PTPN11-mutant JMML. Although dasatinib does not block mutant PTPN11 activity entirely, it is clinically approved for the treatment of other leukemias (CML and ALL), suggesting that its use could be extended to AML and JMML to slow disease progression in patients. The protein tyrosine phosphatase PTPN11 is implicated in the pathogenesis of juvenile myelomonocytic leukemia (JMML), acute myeloid leukemia (AML), and other malignancies. Activating mutations in PTPN11 increase downstream proliferative signaling and cell survival. We investigated the signaling upstream of PTPN11 in JMML and AML cells and found that PTPN11 was activated by the nonreceptor tyrosine/serine/threonine kinase TNK2 and that PTPN11-mutant JMML and AML cells were sensitive to TNK2 inhibition. In cultured human cell–based assays, PTPN11 and TNK2 interacted directly, enabling TNK2 to phosphorylate PTPN11, which subsequently dephosphorylated TNK2 in a negative feedback loop. Mutations in PTPN11 did not affect this physical interaction but increased the basal activity of PTPN11 such that TNK2-mediated activation was additive. Consequently, coexpression of TNK2 and mutant PTPN11 synergistically increased mitogen-activated protein kinase (MAPK) signaling and enhanced colony formation in bone marrow cells from mice. Chemical inhibition of TNK2 blocked MAPK signaling and colony formation in vitro and decreased disease burden in a patient with PTPN11-mutant JMML who was treated with the multikinase (including TNK2) inhibitor dasatinib. Together, these data suggest that TNK2 is a promising therapeutic target for PTPN11-mutant leukemias.
Organizational readiness for implementing change in acute care hospitals as per pdf: An analysis of a cross‐sectional, multicentre study as per pdf

AIM To assess nurse-reported organizational readiness for implementing change in acute care hospitals. BACKGROUND An organization's success at implementing new policies and programmes depends largely on its stakeholders' readiness for change. Organizational readiness is a multilevel, multifaceted construct associated with staffing, leadership and quality of care. DESIGN This is a secondary analysis of the cross-sectional multicentre "Matching Registered Nurse Services with Changing Care Demands" study. METHODS In 23 acute care hospitals across Switzerland, 1,833 nurses working in 124 units completed a survey between September 2015 and January 2016. Organizational readiness was measured with two subscales: "change commitment" and "change efficacy". Work environment factors were assessed using the Practice Environment Scale of the Nursing Work Index. RESULTS Nurses were positive about implementing change in their hospitals. Intraclass correlation was higher at the unit level than at the hospital level for both change commitment and change efficacy. Nursing foundation for quality of care and supportive leadership were positively associated with readiness, change commitment and change efficacy. However, staffing and resource adequacy was positively associated only with change efficacy. No association was found with standardized staffing. CONCLUSION While organizational readiness scores vary among hospitals and units, they are positively associated with supportive leadership and a foundation for quality of care. Further research should consider organizational readiness as an important factor of change and ultimately of the quality of care.
Maternal Lipids at 28 Weeks’ Gestation and Offspring Adiposity at Age 5 to 7 Years

Context Obesity is a global epidemic, and there is a focus on identifying markers of obesity in children with a view to prevention. Objective We aimed to examine prospectively the association of maternal fasting lipids with adiposity in 5- to 7-year-old offspring in a large observational study. Design Pregnant women (1612) were recruited to the Belfast center of the Hyperglycemia and Adverse Pregnancy Outcome study in a large tertiary maternity hospital at an average of 28 weeks' gestation. Maternal fasting total cholesterol, low-density lipoprotein-cholesterol, triglycerides, and high-density lipoprotein-cholesterol were estimated at 28 weeks' gestation. Offspring-mother pairs (819) were included in the current study, and adiposity was expressed as body mass index (BMI) z score (1990 British growth standard) and sum of skin-fold (SSF) thicknesses (triceps, subscapular, and suprailiac). Statistical significance was more rigorously defined as P < 0.01 to allow for multiple comparisons. Results No linear relation was found between maternal lipids and offspring BMI z score or SSFs (P ≥ 0.01) using correlation analysis. With the use of logistic regression, there was no relation between maternal lipids and offspring adiposity controlled for birthweight z score, offspring age, offspring gender, smoking during pregnancy, offspring energy intake and physical activity, maternal BMI during pregnancy, and fasting glucose during pregnancy (P ≥ 0.01). Conclusion Maternal 28-week gestational fasting lipids are not associated with offspring BMI or subcutaneous adiposity at age 5 to 7 years.
Total Synthesis of Keramamides A and L from a Common Precursor by Late-Stage Indole Synthesis and Configurational Revision.

The marine natural products keramamide A and L, members of the class of anabaenopeptin-type peptides, were synthesized for the first time by a convergent and flexible route. The installation of the substituted tryptophan moieties was accomplished at the very end of the synthesis on the cyclic peptides, and thus enabled the synthesis of both natural products from one common precursor. The preparation of several epimers clearly indicates that the originally proposed relative configurations of both Keramamides A and L were not correct.
P3 Component as a Potential Endophenotype for Control Inhibition in Offspring of Alcoholics

Aims To assess inhibitory processes and the ongoing event-related potential (ERP) activity of offspring of alcoholics (OA) during a Go/No-Go task, with the purpose of characterizing possible psychophysiological endophenotypes for alcohol-dependent vulnerability. Short summary EEG recordings and ERP measurements of young adults with positive and negative family history of alcoholism where obtained while they performed a Go/No-Go task to assess inhibitory processes. Offspring of alcoholics showed a different ERP pattern compared to the control group and exerted greater effort than the control group. Methods ERP measurements were obtained by electroencephalogram (EEG) recordings of 65 participants divided into two groups: one group of 30 subjects with positive family history of alcoholism and a control group of 35 subjects with negative family history of alcoholism. They performed a Go/No-Go task, where each individual was required to classify visual stimuli by colour (Go) and inhibit their response to a No-Go signal. Results OA have higher P3 amplitudes during the Go condition in all of the regions analysed and higher No-Go P3 amplitudes than control subjects in the frontal region. Unlike controls, OA have no differences between the P3 amplitudes across conditions. Conclusions The absence of differences between the P3 Go and No-Go observed in the OA group can be interpreted as a possible alteration related with inhibition, in a way that they may need to recruit similar resources for inhibitory and classificational processes for both conditions. Therefore, the P3 component may be considered as a useful endophenotype and a vulnerability marker to develop addictive behaviour.
Analytical and Sample Preparation Protocol for Therapeutic Drug Monitoring of 12 Thiopurine Metabolites Related to Clinical Treatment of Inflammatory Bowel Disease

Thiopurines (TP) represent an important therapeutic tool for the treatment of inflammatory bowel diseases (IBD) in the current situation of rising incidence and health care costs. The results of multiple clinical studies aimed at finding correlations between levels of TP metabolites and response of IBD patients to the treatment are, however, often controversial due to variability in analytical and sample preparation procedures among these studies. In this work, therefore, an updated analytical and sample preparation procedure for therapeutic drug monitoring (TDM) of TP metabolites in blood samples obtained from patients with IBD was proposed to establish a unified protocol. An advanced analytical method based on ion-exchange liquid chromatography hyphenated with tandem mass spectrometry (IEC-ESI-MS/MS) was used for the determination of the profiles of 12 individual TP metabolites in the particular steps of sample preparation procedure including blood collection, red blood cells (RBC) isolation, lysis, and storage. Favorable performance parameters of the IEC-ESI-MS/MS method (LLOQs 1–10 nmol/L, accuracy 95–105%, intra-day and inter-day precision < 10%, selectivity demonstrated via no sample matrix interferences) and acceptable stability (peak area fluctuations < 15%) of clinical samples under the proposed sample preparation conditions {(i) EDTA anticoagulant tube for the blood collection; (ii) 4 °C and 4 h between the sample collection and RBC isolation; (iii) phosphate-buffered saline for RBC washing and re-suspendation; (iv) −20 °C for RBC lysis and short-term storage; (v) 50 mmol/L phosphate buffer, pH 7.4, 10 mmol/L DTT as a stabilizing medium for TPN in RBC lysates} demonstrated the suitability of such protocol for a well-defined and reliable routine use in studies on thiopurines TDM.
Levels of combatant control and the patterns of non-incumbent/insurgent violence experienced by civilians living in Sunni–Arab communities in Iraq (2004–2009)

ABSTRACT This study explores how one social-structural variable, control over Sunni–Arab communities during the Iraq civil war, affected the types of violence used by insurgent/non-government actors that killed and injured civilians in these communities from January 2004 to December 2009. The study classifies three levels of control: (1) incumbent (government-supported) control, (2) insurgent control and (3) actively contested control. It uses Iraq Body Count (IBC) fatality data to characterize two general types of violence (selective and indiscriminate) evident during the Iraq conflict. It demonstrates that the type of violence committed by non-government actors was significantly (P > .01) different as related to the level of control insurgents had over territory. Primarily, insurgents/non-governmental actors used more selective forms of violence when insurgents controlled territory and more indiscriminate violence when incumbent (government-supported) forces controlled territory. Also, acts of indiscriminate violence cause considerably more injuries and death per act as compared to selective violence. Importantly, if control over territory has broadly generalizable effects on the types of violence that civilian’s experience during civil war, than understanding this relationship could be useful when determining the types of medical assistance, medical supplies and training most needed in combat zones.
NLRP3 inflammasome signaling as an early molecular response is negatively controlled by miR-186 in CFA-induced prosopalgia mice

The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is the most frequently studied in the central nervous system and has been linked to neuropathic pain. In this study, a post-translational mechanism of microRNA (miR)-186 via regulating the expression of NLRP3 in the complete Freund's adjuvant (CFA)-treated mice was investigated. The injection of CFA was used to induce trigeminal neuropathic pain in mice. miRs microarray chip assay was performed in trigeminal ganglions (TGs). CFA treatment significantly increased the mRNA expression of NLRP3, interleukin (IL)-1β, and IL-18 in TGs compared to the control group. Moreover, 26 miRs were differentially expressed in TGs from trigeminal neuropathic pain mice, and the expression of miR-186 showed the lowest level of all the miRs. Further examination revealed that NLRP3 was a candidate target gene of miR-186. We delivered miR-186 mimics to CFA-treated mice. The head withdrawal thresholds of the CFA-treated mice were significantly increased by miR-186 mimics injection compared with CFA single treatment. The mRNA and protein expression of NLRP3, IL-1β, and IL-18 in TGs from trigeminal neuropathic pain mice were significantly inhibited by miR-186 mimics treatment compared to the CFA group. miR-186 was able to suppress the neuropathic pain via regulating the NLRP3 inflammasome signaling.