Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetic evaluation of marbofloxacin after intravenous administration at different ages in llama crias, and pharmacokinetic/pharmacodynamic analysis by Monte Carlo simulation

In llama crias (tekes), Escherichia coli and Staphylococcus aureus are major pathogens, and marbofloxacin could be a suitable choice. The objectives of this study were (a) to evaluate the serum pharmacokinetics of marbofloxacin (5 mg/kg) after intravenous administration in tekes and simulate a multidose regimen; (b) to emulate pharmacokinetic profiles after single dose and steady-state conditions by Monte Carlo simulation (c) to determine the MIC of regional strains of Escherichia coli and Staphylococcus aureus; (d) to perform a PK/PD analysis by Monte Carlo simulation. Pharmacokinetics of marbofloxacin was evaluated in six animals at 3, 10, 24, 50, and 80 days after birth. Marbofloxacin were determined by HPLC. A steady-state multi-dose simulation was carried out, and concentration-time profiles were generated by Monte Carlo simulation. MIC of marbofloxacin against regional E. coli and S. aureus strains were also determined. Finally, a PK/PD analysis was conducted by Monte Carlo simulation. After pharmacokinetic analysis, clearance showed a trend to increase (0.14 and 0.18 L kg-1 hr-1 ), and AUC (36.74 and 15.21 μg hr-1 ml-1 ) and Vss (3.06 and 3.37 L/kg) trended to decrease at 3 and 80 days-old, respectively, showing accumulation ~50% in animals with 3 days. All strains tested of E. coli (MIC90 = 0.06 μg/ml) and S. aureus (MIC90 = 0.25 μg/ml) were susceptible to marbofloxacin. PK/PD analysis suggests that the therapeutic regimen of marbofloxacin could be effective for infections caused by E. coli strains in animals between 3 and 80 days, with a CFR for Cmax /MIC > 10 of 100% and for AUC24 /MIC > 125 of 99.99%; and for infections produced by S. aureus in animals between 3 and 24 days old, with a CFR for Cmax /MIC > 10 of 93.08% and for AUC24 /MIC > 60 of 97.01%, but a higher dose should be used in older animals, because PK/PD endpoints were not met.
Screening, Recruitment, and Baseline Characteristics for the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) Study

Background We describe the recruitment of participants for Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE), a large pragmatic cluster randomized trial that is testing the effectiveness of a multifactorial intervention to prevent serious fall injuries. Eligible persons were 70 years or older, community-living, and at increased risk for serious fall injuries. The modified goal was to recruit 5,322 participants over 20 months from 86 primary care practices within 10 diverse health care systems across the United States. Methods The at-risk population was identified using two distinct but complementary screening strategies that included three questions administered centrally via the mail (nine sites) or in the clinic (one site), while recruitment was completed centrally by staff at Yale. Results For central screening, 226,603 letters mailed to 135,118 patients yielded 28,719 positive screens (12.7% of those mailed and 46.5% of the 61,729 returned). In the clinic, 22,537 screens were completed, leading to 5,732 positive screens (25.4%). Of the 34,451 patients who screened positive for high risk of serious fall injuries, 31,872 were sent a recruitment packet and, of these, 5,451 (17.1%) were enrolled over 20 months (mean age: 80 years; 62% female). The participation rate was 34.0% among eligible patients. The enrollment yields were 3.6% (vs 5% projected) for each patient screened centrally, despite multiple screens, and 10.5% (vs 33.9% projected) for each positive clinic screen. Conclusions Despite lower-than-expected yields, the STRIDE Study exceeded its modified recruitment goal. If the STRIDE intervention is found to be effective, the two distinct strategies for identifying a high-risk population of older persons could be implemented by most health care systems.
Stem cell-derived clade F AAVs mediate high-efficiency homologous recombination-based genome editing

Significance Precise genomic correction of pathogenic mutations is an attractive therapeutic strategy. Here, we show that a unique class of stem cell-derived nonpathogenic virus, hematopoietic stem cell-derived adeno-associated virus vector (AAVHSC), mediates precise genome editing at unprecedented efficiencies in primary human cells, including postmitotic cells, and in vivo. Unlike the majority of current editing platforms, genome editing by AAVHSC is uniquely based on homologous recombination (HR), requiring no exogenous nucleases. AAVHSC-mediated editing is seamless, with no evidence of on-target insertion/deletion mutations common to nuclease-based platforms. Efficient in vivo editing was achieved by i.v. injection of AAVHSC editing vectors. The combination of efficient and precise HR-based genome editing coupled with the superior in vivo transduction properties of AAV facilitates progress toward in vivo therapeutic gene editing. The precise correction of genetic mutations at the nucleotide level is an attractive permanent therapeutic strategy for human disease. However, despite significant progress, challenges to efficient and accurate genome editing persist. Here, we report a genome editing platform based upon a class of hematopoietic stem cell (HSC)-derived clade F adeno-associated virus (AAV), which does not require prior nuclease-mediated DNA breaks and functions exclusively through BRCA2-dependent homologous recombination. Genome editing is guided by complementary homology arms and is highly accurate and seamless, with no evidence of on-target mutations, including insertion/deletions or inclusion of AAV inverted terminal repeats. Efficient genome editing was demonstrated at different loci within the human genome, including a safe harbor locus, AAVS1, and the therapeutically relevant IL2RG gene, and at the murine Rosa26 locus. HSC-derived AAV vector (AAVHSC)-mediated genome editing was robust in primary human cells, including CD34+ cells, adult liver, hepatic endothelial cells, and myocytes. Importantly, high-efficiency gene editing was achieved in vivo upon a single i.v. injection of AAVHSC editing vectors in mice. Thus, clade F AAV-mediated genome editing represents a promising, highly efficient, precise, single-component approach that enables the development of therapeutic in vivo genome editing for the treatment of a multitude of human gene-based diseases.
Paternal lifestyle factors in relation to semen quality and in vitro reproductive outcomes

This prospective‐cohort study aimed at investigating the influence of paternal lifestyle factors on semen parameters and intracytoplasmic sperm injection (ICSI) outcomes. The influence of paternal lifestyle factors on seminal quality and ICSI outcomes was investigated in male patients undergoing conventional semen analysis. Cigarette smoking negatively influenced semen volume (B: −0.417, slope: 1.570, p = 0.047), sperm count/ml (B: −7.363, slope: 52.298, p = 0.014), total sperm count (B: −4.43, slope: 178.165, p = 0.023), total motile sperm count (B: −1.38, slope: 100.276, p = 0.045) and SDF (B: 0.014, slope: 9.767, p = 0.033). Alcohol consumption negatively influenced sperm count/ml (B: −12.527, slope: 42.255, p = 0.040) and sperm DNA fragmentation (B: 5.833, slope: 9.680, p = 0.002). There were no significant influences of other paternal lifestyle factors. Cigarette smoking negatively influenced the fertilisation rate (B: −1.349, slope: 21.950, p = 0.039) and the blastocyst formation rate (B: −14.244, slope: 28.851, p = 0.025). Alcohol consumption negatively influenced fertilisation rate (B: −3.617, slope: 20.138, p = 0.041) and blastocyst formation rate (B: −34.801, slope: 30.044, p = 0.042). Cigarette smoking and alcohol consumption appear to reduce semen quality, fertilisation and blastocyst formation rates; thus, it would be wise to recommend that male partners reconsider their lifestyle during in vitro reproduction treatment.
The ambulance nurse experiences of non‐conveying patients

Abstract Aims and objectives To explore ambulance nurses' (ANs) experiences of non‐conveying patients to alternate levels of care. Background Increases in ambulance utilisation and in the number of patients seeking ambulance care who do not require medical supervision or treatment during transport have led to increased nonconveyance (NC) and referral to other levels of care. Design A qualitative interview study was conducted using an inductive research approach. Methods The study was conducted in a region in the middle of Sweden during 2016–2017. Twenty nurses were recruited from the ambulance departments in the region. A conventional content analysis was used to analyse the interviews. The study followed the COREQ checklist. Results The ANs experienced NC as a complex and difficult task that carried a large amount of responsibility. They wanted to be professional, spend time with the patient and find the best solution for him or her. These needs conflicted with the ANs' desire to be available for assignments with a higher priority. The ANs could feel frustrated when they perceived that ambulance resources were being misused and when it was difficult to follow the NC guidelines. Conclusion If ANs are expected to nonconvey patients seeking ambulance care, they need a formal mandate, knowledge and access to primary health care. Relevance to clinical practice This study provides new knowledge regarding the work situation of ANs in relation to NC. These findings can guide future research and can be used by policymakers and ambulance organisations to highlight areas that need to evolve to improve patient care.
The Genomics of Sexual Conflict*

Sexual dimorphism is a substantial contributor to the diversity observed in nature, extending from elaborate traits to the expression level of individual genes. Sexual conflict and sexually antagonistic coevolution are thought to be central forces driving the dimorphism of the sexes and its diversity. We have substantial data to support this at the phenotypic level but much less at the genetic level, where distinguishing the role of conflict from other forms of sex-biased selection and from other processes is challenging. Here we discuss the powerful effects sexual conflict may have on genome evolution and critically evaluate the supporting evidence. Although there is much potential for sexual conflict to affect genome evolution, we have relatively little compelling evidence of a genomic signature of sexual conflict. A central obstacle is the mismatch between taxa in which we understand sexually antagonistic selection and those in which we understand genetics.
Deficiency in Fpr2 results in reduced numbers of Lin−cKit+Sca1+ myeloid progenitor cells

The Lin−c-Kit+ Sca-1+ cell population in the bone marrow (BM) serves as the direct precursor for differentiation of myeloid cells. In this study, we report that deficiency in Fpr2, a G protein–coupled chemoattractant receptor in mice, is associated with reduced BM nucleated cells, including CD31+Ly6C+ (granulocytes and monocytes), CD31−/Ly6Cint (granuloid cells), and CD31−/Ly6Chigh (predominantly monocytes) cells. In particular, the number of Lin−c-Kit+Sca-1+ (LKS) cells was reduced in Fpr2−/− mouse BM. This was supported by observations of the reduced incorporation of intraperitoneally injected bromodeoxyuridine by cells in the c-Kit+ population from Fpr2−/− mouse BM. Purified c-Kit+ cells from Fpr2−/− mice showed reduced expansion when cultured in vitro with stem cell factor (SCF). SCF/c-Kit-mediated phosphorylation of P38, STAT1, Akt (Thr-308), and Akt (Ser-473) was also significantly reduced in c-Kit+ cells from Fpr2−/− mice. Furthermore, Fpr2 agonists enhanced SCF-induced proliferation of c-Kit+ cells. Colony-forming unit assays revealed that CFU–granulocyte–macrophage formation of BM cells from Fpr2−/− mice was significantly reduced. After heat-inactivated bacterial stimulation in the airway, the expansion of c-kit+ Sca-1+ cells in BM and recruitment of Ly6G+ cells to the lungs and CD11b+Ly6C+TNFα+ cells to the spleen of Fpr2−/− mice was significantly reduced. These results demonstrate an important role for Fpr2 in the development of myeloid lineage precursors in mouse BM.
Long-term outcomes after group B streptococcus infection: a cohort study

Objective To describe the risk of death and hospitalisation until adolescence of children after group B streptococcus (GBS) infection during infancy. Design Population-based cohort study. Setting New South Wales, Australia. Patients All registered live births from 2000 to 2011. Interventions Comparison of long-term outcomes in children with the International Statistical Classification of Diseases and Related Health Problems-10th Revision discharge codes corresponding to GBS infections and those without. Main outcome measures Death and hospitalisation. Results A total of 1206 (0.1%) children (936 (77.6%)≥37 weeks’ gestation) were diagnosed with GBS infection. Over the study period, infection rates decreased from 2.1 (95% CI 1.8 to 2.4) to 0.7 (95% CI 0.5 to 0.9) per 1000 live births. Infants with GBS infection were born at lower gestation (mean 37.6 vs 39.0 weeks), were more likely very low birth weight (<1500 g, OR 9.1(95% CI 7.4 to 11.3)), born premature (OR 3.9(95% CI 3.4 to 4.5)) and have 5 min Apgar scores ≤5 (OR 6.7(95% CI 5.1 to 8.8)). Children with GBS had three times the adjusted odds of death (adjusted OR (AOR) 3.0(95% CI 2.1 to 4.3)) or rehospitalisations (AOR 3.1(95% CI 2.7 to 3.5)). Thirty-six (3.0%) with GBS died, with >50% of deaths occurring <28 days. Children with GBS were hospitalised more frequently (median 2 vs 1), for longer duration (mean 3.7 vs 2.2 days) and were at higher risk for problems with genitourinary (OR 3.1(95% CI 2.8 to 3.5)) and nervous (OR 2.0 (95% CI1.7 to 2.3)) systems. Conclusions Despite decreasing GBS rates, the risk of poor health outcomes for GBS-infected children remains elevated, especially during the first 5 years. Survivors continue to be at increased risk of death and chronic conditions requiring hospitalisations, such as cerebral palsy and epilepsy.
Which interventions work for dementia family carers?: an updated systematic review of randomized controlled trials of carer interventions

ABSTRACT Objective: The aim of this study was to update the literature on interventions for carers of people with dementia published between 2006 and 2016 and evaluate the efficacy of psychoeducational programs and psychotherapeutic interventions on key mental health outcomes (depression, anxiety, burden, and quality of life). Methods: A meta-analysis was carried out of randomized controlled trials of carer interventions using MEDLINE, PsycINFO, Scopus, and Cochrane Central Register of Controlled Trials. Results: The majority of studies were conducted in Western and Southern Europe or the United States and recruited carers of people with Alzheimer's disease or dementia grouped as a whole. The most commonly used outcome measures were depression and burden across studies. The updated evidence suggested that psychoeducation-skill building interventions delivered face-to-face can better impact on burden. Psychotherapeutic interventions underpinned by Cognitive Behavior Therapy (CBT) models demonstrated strong empirical support for treating anxiety and depression and these effects were not affected by the mode of delivery (i.e. face-to-face vs. technology). A modern CBT approach, Acceptance and Commitment Therapy (ACT), seemed to be particularly beneficial for carers experiencing high levels of anxiety. Conclusions: Future research needs to explore the efficacy of interventions on multiple clinical outcomes and which combination of interventions (components) would have the most significant effects when using CBT. The generalization of treatment effects in different countries and carers of different types of dementia also need to be addressed. More research is needed to test the efficacy of modern forms of CBT, such as ACT.
Care and Discharge Outcome of Acute Stroke in Lebanon: A Hospital-Based Study

Abstract The present study was conducted to assess stroke care and outcomes in two Lebanese hospitals. Patients admitted in 2012 and 2013 were retrospectively selected. Data were extracted from medical records for time to hospital arrival, stroke severity, management, and discharge outcomes. A Cox regression analysis was then conducted to predict time to in-hospital death. A total of 201 patients were included (mean age = 69.2 years), among whom 50% arrived within a delay of 3.75 hours. Half underwent brain imaging in the first hour, and nine patients received an acute intervention. Forty-four patients died at the hospital; 142 were discharged home, among whom 98 patients were dependent in their daily activities. Stroke severity on admission and time from onset to arrival were found to be significantly associated to the time to in-hospital death (adjusted hazard ratio [HRa] = 1.13 and HRa = 0.98 respectively; p < 0.05). The study sheds light on high case fatality and dependency rates at discharge among stroke patients in Lebanese hospitals.
Serotonin transporter (5‐HTTLPR) genotypes and trinucleotide repeats of androgen receptor exert a combinatorial effect on hormonal milieu in patients with lifelong premature ejaculation

Premature ejaculation is one of the most common sexual disorders in men due to uncontrolled modulation of spinal reflexes controlled by cortico‐limbic centers in the brain. In this study, we investigate the combinatorial effects of trinucleotide repeats of androgen receptor and allelic variants of the 5‐HTTLPR gene on sex steroids, hypophyseal hormones, sexual performance, and premature ejaculation assessment parameters among evidence‐based lifelong premature ejaculation subjects. A total of 271 outpatients (age 26.6 ± 1.9) consulting for evidence‐based lifelong premature ejaculatory dysfunction were selected in this study. The control group consists of 155 men with normal IELT (>4 min). The study revealed that the subjects who have the highest (≥26) CAG stretches depicted a significantly higher serum oxytocin levels (102.1 pg/ml; n = 126, p < 0.001) compared with the control group (71.2 pg/ml; n = 75, p = <0.001) and patients which have medium (22–25) and short (≤21) CAG stretches (76.63 ng/ml; n = 64, p < 0.001 vs. 77.4 ng/ml; n = 81, p < 0.001). Almost 33 (26.1%) lifelong premature ejaculatory patients had AR variant of longer (≥26) CAG repeats was homozygous for S alleles (SS), 45 (35.7%) was homozygous for L allele (LL), and 48 (38%) had the L/S or S/L genotype of 5‐HTTLPR gene. Homozygous (SS) alleles have a significant positive correlation (r = 0.44, p < 0.0001) with the high score of BDI‐II (39.1, n = 126, p < 0.001). However, LL alleles have shown a significant positive correlation with PEDT (r = 0.46, p < 0.001) and negative correlation with self‐estimated IELT and intercourse satisfaction (r = −0.35, p < 0.001). The innovative study design elaborates that androgen receptor trinucleotide repeats and 5‐HTTLPR genotypes have combinatorial impact on hormonal milieu and sexual function regarding evidence‐based lifelong premature ejaculatory dysfunction patients.
Potential risk factors associated with prognosis of neoadjuvant chemotherapy followed by interval debulking surgery in stage IIIc–IV high‐grade serous ovarian carcinoma patients

No consensus has been achieved on the prognostic factors for patients with advanced stage epithelial ovarian cancer who underwent neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS). This study aimed to investigate the prognostic factors for the patients diagnosed as International Federation of Gynecology and Obstetrics stage IIIc–IV high‐grade serous ovarian cancer (HG‐SOC).
Screening for infectious diseases in newly arrived migrants in Europe: the context matters

In the past three decades there has been a considerable increase in the number of migrants globally. In 2015, about one third of the world’s migrants lived in Europe (ca 75 million, which is about 10% of the area’s population), contributing to the region’s economy and creating a younger demographic composition [1,2]. In recent years, an unprecedented number of forcibly displaced persons fleeing conflict, violence or disaster have come to Europe. In 2015, the peak year of this wave, more than one million asylum seekers, refugees and irregular migrants arrived in Europe [3]. For the purpose of this editorial, economic immigrants, asylum seekers and refugees are collectively referred to herein as migrants.
Ixazomib: An Oral Proteasome Inhibitor for the Treatment of Multiple Myeloma

The FDA approval of ixazomib for use in combination with lenalidomide and dexamethasone for patients with multiple myeloma who have received at least one prior therapy signalled the arrival of the first oral proteasome inhibitor, allowing advanced practitioners to provide multiple myeloma patients an exclusively oral triplet therapy.
Clinical factors that affect diagnostic discrepancy between colposcopically directed biopsies and loop electrosurgical excision procedure conization of the uterine cervix

Objective This study aimed to determine the factors affecting pathologic discrepancy and final diagnosis between colposcopic biopsy and pathology by loop electrosurgical excision procedure (LEEP). Methods Between 2004 and 2016, 1,200 patients who underwent LEEP were enrolled for this study. 667 underwent cervical cytology, human papillomavirus (HPV) test, colposcopic biopsy, and LEEP. We analyzed patient's age, menopausal status, number of delivery, abortion times, cervical cytology, number of punch biopsies, HPV type, LEEP, and interval between colposcopic biopsy and LEEP. Results Logistic regression analysis of the final diagnosis showed that age 30–39 years and other high HPV group types were associated with cancer diagnosis, whereas atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H), high-grade squamous intraepithelial lesion (HSIL), and HPV type 16 affected the diagnosis of cervical intraepithelial neoplasia (CIN) 2. The overall concordance rate of histopathology between punch biopsy and LEEP was 43.3%. The rates of detecting a more severe lesion by LEEP than those by biopsy were 23.1%. The rates of a less severe lesion detected by LEEP than those by biopsy were 33.6%. Factors related with biopsy underestimation were as follows: <1 vaginal delivery, HSIL, number of punch biopsies and HPV type. Punch biopsy number is a unique factor of biopsy overestimation. Conclusion Patients with ASC-H, HSIL, and HPV type 16 may undergo conization immediately without colposcopic biopsy. We suggest that colposcopically directed 3 to 5 punch biopsies may be used to determine the need for conization.
New ABCC2 rs3740066 and rs2273697 Polymorphisms Identified in a Healthy Colombian Cohort

Multidrug resistance-associated proteins (MRP) 1 and 2 belong to the ABC (ATP-Binding Cassette) transporters. These transport proteins are involved in the removal of various drugs and xenobiotics, as well as in multiple physiological, pathological, and pharmacological processes. There is a strong correlation between different polymorphisms and their clinical implication in resistance to antiepileptic drugs, anticancer, and anti-infective agents. In our study, we evaluated exon regions of MRP1 (ABCC1)/MRP2 (ABCC2) in a Colombian cohort of healthy subjects to determine single nucleotide polymorphisms (SNPs) and to determine the allelic and genomic frequency. Results showed there are SNPs in our population that have been previously reported for both MRP1/ABCC1 (rs200647436, rs200624910, rs150214567) and MRP2/ABCC2 (rs2273697, rs3740066, rs142573385, rs17216212). Additionally, 13 new SNPs were identified. Evidence also shows a significant clinical correlation for polymorphisms rs3740066 and rs2273697 in the transport of multiple drugs, which suggests a genetic variability in regards to that reported in other populations.