bluuebunny/crossref_metadata_2025_split huggingface dataset:
An approach for evaluating early and long term mother-to-child transmission of HIV (MTCT) in low and middle income countries: a South African experience
Authors: Jackson Debra J. , Dinh Thu-Ha , Lombard Carl J. , Sherman Gayle G. , Goga Ameena E. 
Published: September 2019

Abstract

Background
Eliminating mother-to-child transmission of HIV is a global public health target. Robust, feasible methodologies to measure population level impact of programmes to prevent mother-to-child transmission of HIV (PMTCT) are needed in high HIV prevalence settings. We present a summary of the protocol of the South African PMTCT Evaluation (SAPMTCTE) with its revision over three repeated rounds of the survey, 2010–2014.

Methods
Three cross sectional surveys (2010, 2011–2012 and 2012–2013) were conducted in 580 primary health care immunisation service points randomly selected after stratified multistage probability proportional to size sampling. All infants aged 4–8 weeks receiving their six-week immunisation at a sampled facility on the day of the visit were eligible to participate. Trained research nurses conducted interviews and took infant dried blood spot (iDBS) samples for HIV enzyme immunoassay (EIA) and total nucleic acid polymerase chain reaction (PCR) testing. Interviews were conducted using mobile phones and iDBS were sent to the National Health Laboratory for testing. All findings were adjusted for study design, non-response, and weighted for number of South African live-birth in each study round. In 2012 a national closed cohort of these 4 to 8-week old infants testing EIA positive (HIV Exposed Infants) from the 2012–2013 cross-sectional survey was established to estimate longer-term PMTCT impact to 18 months. Follow-up analyses were to estimate weighted cumulative MTCT until 18 months, postnatal MTCT from 6 weeks until 18 months and a combined outcome of MTCT-or-death, using a competing risks model, with death as a competing risk. HIV-free survival was defined as a child surviving and HIV-negative up to 18 months or last visit seen. A weighted cumulative incidence analysis was conducted, adjusting for survey design effects.

Discussion
In the absence of robust high-quality routine medical recording systems, in the context of a generalised HIV epidemic, national surveys can be used to monitor PMTCT effectiveness; however, monitoring long-term outcomes nationally is difficult due to poor retention in care.
Infrastructural and human-resource factors associated with return of infant HIV test results to caregivers: secondary analysis of a nationally representative situational assessment, South Africa, 2010
Authors: Ngandu Nobubelo Kwanele , Maduna Vincent , Sherman Gayle , Noveve Nobuntu , Chirinda Witness , Ramokolo Vundli , Lombard Carl , Goga Ameena Ebrahim 
Published: September 2019

AbstractBackgroundIn June 2015, South Africa introduced early infant HIV diagnosis (EID) at birth and ten weeks postpartum. Guidelines recommended return of birth results within a week and ten weeks postpartum results within four weeks. Task shifting was also suggested to increase service coverage. This study aimed to understand factors affecting return of EID results to caregivers.MethodsSecondary analysis of data gathered from 571 public-sector primary health care facilities (PHCs) during a nationally representative situational assessment, was conducted. The assessment was performed one to three months prior to facility involvement in the 2010 evaluation of the South African programme to prevent mother-to-child HIV transmission (SAPMTCTE). Self-reported infrastructural and human resource EID-related data were collected from managers and designated staff using a structured questionnaire. The main outcome variable was ‘EID turn-around-time (TAT) to caregiver’ (caregiver TAT), measured as reported number of weeks from infant blood draw to caregiver receipt of results. This was dichotomized as either short (≤3 weeks) or delayed (> 3 weeks) caregiver TAT. Logit-based risk difference analysis was used to assess factors associated with short caregiver TAT. Analysis included TAT to facility (facility TAT), defined as reported number of weeks from infant blood draw to facility receipt of results.ResultsOverall, 26.3% of the 571 PHCs reported short caregiver TAT. In adjusted analyses, short caregiver TAT was less achieved when facility TAT was > 7 days (versus ≤7 days) (adjusted risk difference (aRD): − 0.2 (95% confidence interval − 0.3-(− 0.1)),p = 0.006 for 8–14 days and − 0.3 (− 0.5-(− 0.1)), p = 0.006 for > 14 days), and in facilities with staff nurses (compared to those without) (aRD: − 9.4 (− 16.6-(− 2.2),p = 0.011).ConclusionAlthough short caregiver TAT for EID was only reported in approximately 26% of facilities, these facilities demonstrate that achieving EID TAT of ≤3 weeks is possible, making timely ART initiation within 3 weeks of diagnosis feasible within the public health sector. Our adjusted analyses underpin the need for quick return of results to facilities. They also raise questions around staff mentoring: we hypothesise that facilities with staff nurses were likely to have fewer professional nurses, and thus inadequate senior support.
Clinical, neuroimaging, biochemical, and genetic features in six Chinese patients with Adrenomyeloneuropathy
Authors: Li Jie , Wang Hongfen , He Zizi , Wang Xiangqing , Tang Jing , Huang Dehui 
Published: September 2019

Abstract

Background
Adrenoleukodystrophy is a rare neurogenetic disease, AMN is the most common adult phenotype, such patients in China have not gotten enough attention. This article aims to study the features of AMN in Chinese patients and expand the gene spectrum of Chinese X-linked adrenoleukodystrophy (X-ALD) patients.

Methods
We applied clinical analysis, radiology, plasma levels of very long chain fatty acids (VLCFA) and genetic analysis to test the 6 Chinese AMN patients.

Results
All 6 patients are men. Ages of neurological symptom onset are distributed between 21 and 38. Sexual dysfunction occurred in 5 of 6 patients. Three patients had positive family history. Five patients had Addison’s disease. Four patients were diagnosed as pure AMN, while the other two patients were with cerebral involvement. Four patients had abnormalities of nerve conduction studies. There were four patients with central conduction defects in somatosensory evoked potential tests. All 6 patients were found diffuse cord atrophy in spinal MRI. Brain MRI showed abnormal signals in 2 of the 6 tested patients, which indicated the clinical phenotypes. Plasma levels of VLCFA, as well as C24:0/C22:0 and C26:0/C22:0 ratios were elevated in 5 tested patients. Five different ABCD1 mutations were identified in 5 tested patients, one of which was a de novo mutation, and the other four have been reported previously.

Conclusion
This research described the clinical, neuroimaging, biochemical, and genetic sides of Chinese AMN patients. A de novo mutation in the ABCD1 gene sequence was identified. Emotional trauma may trigger or aggravate the development of cerebral demyelination in AMN patients. Regular evaluation of brain MRI is important for AMN patients, especially for ‘pure AMN’ patients. When encountering patients with ‘myeloneuropathy-only’, neurologists should not ignore the tests of VLCFA or/and the ABCD1 gene.
Maternal pre-pregnancy body mass index, smoking in pregnancy, and alcohol intake in pregnancy in relation to pubertal timing in the children
Authors: Brix Nis , Ernst Andreas , Lauridsen Lea Lykke Braskhøj , Parner Erik Thorlund , Arah Onyebuchi A. , Olsen Jørn , Henriksen Tine Brink , Ramlau-Hansen Cecilia Høst 
Published: September 2019

Abstract

Background
Earlier pubertal timing has been observed in many countries. We aimed to explore if prenatal exposure to maternal obesity, smoking, and alcohol intake was associated with timing of puberty by use of a novel marker of pubertal timing: ‘the height difference in standard deviations’ (HD:SDS).

Methods
HD:SDS is the difference between pubertal height in standard deviations and adult height in standard deviations, and it correlates well with age at peak height velocity. Pubertal height was measured by health care professionals at approximately 13 years in boys and 11 years in girls, and the children’s adult height was predicted from parental height reported by the mothers during pregnancy. Information on HD:SDS was available for 42,849 of 56,641 eligible boys and girls from the Danish National Birth Cohort born 2000–2003. In a subsample, HD:SDS was validated against age at the following self-reported pubertal milestones: Tanner stages, menarche, first ejaculation, voice break, acne, and axillary hair. Prenatal exposures were reported by mothers during pregnancy.

Results
HD:SDS correlated moderately with the pubertal milestones considered (correlation coefficients: − 0.20 to − 0.53). With normal weight (body mass index (BMI): 18.5–24.9 kg/m2) as the reference, maternal pre-pregnancy obesity (BMI: 30.0+ kg/m2) was associated with earlier pubertal timing: 0.23 (95% confidence interval (CI): 0.18, 0.28) higher HD:SDS in boys and 0.19 (95% CI, 0.14, 0.24) higher HD:SDS in girls. Maternal smoking was not associated with pubertal timing. Compared to alcohol abstainers, maternal intake of > 3 units of alcohol weekly was associated with later puberty in boys only: 0.14 (95% CI, 0.05, 0.24) lower HD:SDS.

Conclusion
As correlations between HD:SDS and the considered pubertal milestones were comparable to those reported in the literature between age a peak height velocity and the considered pubertal milestones, the validity of HD:SDS seems acceptable. Maternal pre-pregnancy obesity was associated with earlier pubertal timing in both sexes, and maternal alcohol intake during pregnancy was associated with later pubertal timing in boys. Maternal smoking has been linked to earlier timing of puberty, but this was not replicated in our setting using HD:SDS as a marker of pubertal timing.
Development and validation of a prediction model for knee joint line orientation after high tibial osteotomy
Authors: Park Jae-Young , Chang Chong Bum , Kang Dong-Wan , Oh Sohee , Kang Seung-Baik , Lee Myung Chul 
Published: September 2019

AbstractBackgroundMaintenance of optimal knee joint line orientation (KJLO) is important after high tibial osteotomy (HTO). No tools, however, are currently available that could predict the value of postoperative KJLO before surgery. First, this study sought to determine the effects of various preoperative anatomical alignment parameters to postoperative KJLO. Based upon these analyses, we aimed to devise an equation that predicts the value of postoperative KJLO.MethodsA total of 14 radiographic parameters were measured in preoperative and postoperative full-limb standing anteroposterior radiographs on 50 patients who underwent open-wedge HTO. The parameters were analysed using multivariable linear regression to predict KJLO after HTO. External validation of the equation was done with 20 patients who underwent HTO at another institution.ResultsAfter HTO, KJLO increased from − 0.8° to 2.9° (P < 0.001). Based on the multivariable linear regression analysis, an equation was derived that can estimate postoperative KJLO after HTO; postoperative KJLO(°) = 1.029 + 0.560 × preoperative KJLO(°) + 0.310 × preoperative tibia plateau inclination(°) + 0.463 × aimed correction angle(°). The adjusted coefficients of determination value for this equation was 0.721. The equation also showed good calibration and predictability in external validation with predicted squared correlation coefficient of 0.867.ConclusionsThis study analysed the effects of preoperative anatomical alignment parameters on the postoperative KJLO. An equation which predicts postoperative KJLO with preoperative anatomical alignment factors was devised and validated. This equation would help in selecting optimal patients for HTO and in selecting the optimal target correction angle in HTO.
A cross-sectional and 6-year follow-up study of associations between leisure time physical activity and vertebral fracture in adults
Authors: Mikkilä Saija , Calogiuri Giovanna , Emaus Nina , Morseth Bente 
Published: September 2019

Abstract

Introduction
Vertebral fractures are common osteoporotic fractures, affecting 2–46% of the population, causing morbidity and increased risk of mortality. Physical activity has beneficial effects for bone health, including increased bone mineral density and reduced hip fractures. However, evidence concerning prevention of vertebral fractures is scarce. Therefore, the aim of this study was to investigate the association between leisure time physical activity and vertebral fracture risk.

Methods
The data were retrieved from the 2001 and 2007–2008 surveys of the Tromsø Study, a longitudinal population study in Norway. A total of 1904 participants (1030 women and 874 men, age 38–87 yr and 40–87 yr respectively) were included in the cross-sectional analysis (2007–2008). Prospective follow-up data (2001 to 2007) on physical activity were available for 1131 participants (636 women and 495 men, age 32–69 yr and 33–69 yr respectively). Physical activity was assessed by a questionnaire and vertebral fracture by lateral vertebral fracture assessment from dual-energy x-ray absorptiometry scans. Logistic regression was used to examine associations between physical activity and vertebral fracture.

Results
After controlling for confounders (age, height, weight, smoking, osteoporosis, osteoporosis medication, left hip total bone mineral density, and use of hormones in women only), no cross-sectional associations between physical activity levels and vertebral fracture were observed, OR 1.13 (95% CI: 0.59–2.13), for moderately active women and 1.44 (0.61–3.42) for highly active women, compared with sedentary women. In men, the respective ORs were 1.74 (95% CI: 0.91–3.35) and 1.64 (0.78–3.41). In the prospective analyses, OR for vertebral fracture in women with reduced physical activity was 0.81 (95% CI: 0.18–3.62), 1.24 (95% CI: 0.29–5.26) for increased physical activity and 1.54 (95% CI: 0.43–5.50) for active unchanged physical activity pattern, compared with sedentary unchanged physical activity. In men, the respective ORs were 2.05 (95% CI: 0.57–7.42), 2.23 (95% CI: 0.63–7.87), and 1.81 (95% CI: 0.54–6.02). Subanalyses of women and men ≥50 yr showed similar results.

Conclusions
Our findings suggest that physical activity does not play a major role in preventing vertebral fractures in Norwegian adults. Future studies may benefit from data on incident vertebral fracture, and objectively measured physical activity.
Improved long-term cardiovascular outcomes after intensive versus standard screening of diabetic complications: an observational study
Authors: Morieri Mario Luca , Longato Enrico , Mazzucato Marta , Di Camillo Barbara , Cocchiglia Arianna , Gubian Lorenzo , Sparacino Giovanni , Avogaro Angelo , Fadini Gian Paolo , Vigili de Kreutzenberg Saula 
Published: September 2019

Abstract

Background
Complication screening is recommended for patients with type 2 diabetes (T2D), but the optimal screening intensity and schedules are unknown. In this study, we evaluated whether intensive versus standard complication screening affects long-term cardiovascular outcomes.

Methods
In this observational study, we included 368 T2D patients referred for intensive screening provided as a 1-day session of clinical–instrumental evaluation of diabetic complications, followed by dedicated counseling. From a total of 4906 patients, we selected control T2D patients who underwent standard complication screening at different visits, by 2:1 propensity score matching. The primary endpoint was the 4p-MACE, defined as cardiovascular mortality, or non-fatal myocardial infarction, stroke, or heart failure. The Cox proportional regression analyses was used to compare outcome occurrence in the two groups, adjusted for residual confounders.

Results
357 patients from the intensive screening group (out of 368) were matched with 683 patients in the standard screening group. Clinical characteristics were well balanced between the two groups, except for a slightly higher prevalence of microangiopathy in the intensive group (56% vs 50%; standardized mean difference 0.11, p = 0.1). Median follow-up was 5.6 years. The adjusted incidence of 4p-MACE was significantly lower in the intensive versus standard screening group (HR 0.70; 95% CI 0.52–0.95; p = 0.02). All components of the primary endpoint had nominally lower rates in the intensive versus standard screening group, which was particularly significant for heart failure (HR 0.43; 95% CI 0.22–0.83; p = 0.01).

Conclusion
Among T2D patients attending a specialist outpatient clinic, intensive complication screening is followed by better long-term cardiovascular outcomes. No significant effect was noted for cardiovascular and all-cause mortality and the benefit was mainly driven by a reduced rate of hospitalization for heart failure.
Improvement of Fab expression by screening combinatorial synonymous signal sequence libraries
Authors: Kulmala Antti , Huovinen Tuomas , Lamminmäki Urpo 
Published: September 2019

Abstract

Background
Antibody fragments can be expressed in Escherichia coli, where they are commonly directed to the periplasm via Sec pathway to enable disulphide bridge formations and correct folding. In order to transport antibody fragments to the periplasmic space via Sec pathway, they are equipped with N-terminal signal sequence. Periplasmic expression has many benefits but it’s also subjected to many hurdles like inefficient translocation across the inner membrane and insufficient capacity of the translocation system. One solution to overcome these hurdles is a modulation of codon usage of signal sequence which has proved to be an efficient way of tuning the translocation process. Modulation of codon usage of signal sequences has been successfully employed also in improving the expression levels of antibody fragments, but unfortunately the effect of codon usage on the expression has not been thoroughly analyzed.

Results
In the present study we established three synonymous PelB signal sequence libraries by modulating codon usage of light chain and heavy chain PelB signal sequences of a Fab fragment. Each region (n-region, hydrophobic region and c-region) of the PelB signal sequence in the both chains of the Fab fragment in a bicistronic expression vector was mutated separately. We then screened for clones with improved expression profile. The best source for improved clones was the n-region library but in general, improved clones were obtained from all of the three libraries. After screening, we analyzed the effects of codon usage and mRNA secondary structures of chosen clones on the expression levels of the Fab fragment. When it comes to codon usage based factors, it was discovered that especially codon usage of fifth leucine position of the light chain PelB affects the expression levels of Fab fragment. In addition, we observed that mRNA secondary structures in the translation initiation regions of the light and heavy chain have an effect on expression levels as well.

Conclusions
In conclusion, the established synonymous signal sequence libraries are good sources for discovering Fab fragments with improved expression profile and obtaining new codon usage related information.
Role of the dynamic tumor microenvironment in controversies regarding immune checkpoint inhibitors for the treatment of non-small cell lung cancer (NSCLC) with EGFR mutations
Authors: Lin Anqi , Wei Ting , Meng Hui , Luo Peng , Zhang Jian 
Published: September 2019

AbstractImmunotherapy has been incorporated into the first- and second-line treatment strategies for non-small cell lung cancer (NSCLC), profoundly ushering in a new treatment landscape. However, both adaptive signaling and oncogenic (epidermal growth factor receptor (EGFR)-driven) signaling may induce PD-L1 upregulation in NSCLC. Nevertheless, the superiority of immune checkpoint inhibitors (ICIs) in advanced EGFR-mutant NSCLC is only moderate. ICIs appear to be well tolerated, but clinical activity for some advanced EGFR-mutant NSCLC patients has only been observed in a small proportion of trials. Hence, there are still several open questions about PD-L1 axis inhibitors in patients with NSCLC whose tumors harbor EGFR mutations, such as the effect of EGFR tyrosine kinase inhibitors (TKIs) or EGFR mutations in the tumor microenvironment (TME). Finding the answers to these questions requires ongoing trials and preclinical studies to identify the mechanisms explaining this possible increased susceptibility and to identify prognostic molecular and clinical markers that may predict benefits with PD-1 axis inhibition in this specific NSCLC subpopulation. The presence of multiple mechanisms, including dynamic immune TME profiles, changes in PD-L1 expression and low tumor mutational burdens, may explain the conflicting data regarding the correlation between PD-L1 axis inhibitors and EGFR mutation status. We conducted a review of this currently controversial topic in an attempt to aid in the decision-making process.
Long-term statin persistence is poor among high-risk patients with dyslipidemia: a real-world administrative claims analysis
Authors: Toth Peter P. , Granowitz Craig , Hull Michael , Anderson Amy , Philip Sephy 
Published: September 2019

AbstractBackgroundA decade ago, statin persistence was < 50% after 1 year, and recent short-term analyses have revealed very little progress in improving statin persistence, even in patients with a prior cardiovascular (CV) event. Data on longer-term statin persistence are lacking. We measured long-term statin persistence in patients with high CV risk.MethodsThis retrospective administrative claims analysis of the Optum Research Database included patients aged ≥ 45 years with diabetes and/or atherosclerotic CV disease (ASCVD) who had a statin prescription filled in 2010. It included an elevated triglycerides (TG) cohort of patients with index date in 2010 and TG ≥ 150 mg/dL (n = 23,181) and a propensity-matched comparator cohort with TG < 150 mg/dL and high-density lipoprotein cholesterol > 40 mg/dL (n = 23,181). Both cohorts were followed for ≥ 6 months up to March 2016.ResultsThe probability of remaining on a prescription fill for index statin therapy was 47% after 1 year and 19% after 5 years in both cohorts. Statin persistence was worse among women than men, and among younger versus older patients (P < 0.001 for all comparisons). After 5 years, the probability of remaining on a prescription fill for index statin was < 25% across all subgroups assessed including patients with and without baseline revascularization, heart failure, peripheral artery disease and renal disease. Similar results were observed in a subcohort analysis of patients with TG 200–499 mg/dL.ConclusionsLong-term statin persistence after 5 years is alarmingly low (< 25%) and is a public health concern.