Miracle-dz/UniFAR-FTUs huggingface dataset:
Leucine rich repeat kinase 2 (LRRK2) GLY2019SER mutation is absent in a second cohort of Nigerian Africans with Parkinson disease

To date the LRRK2 p.G2019S mutation remains the most common genetic cause of Parkinson disease (PD) worldwide. It accounts for up to 6% of familial and approximately 1.5% of sporadic cases. LRRK2 has a kinase enzymatic domain which provides an attractive potential target for drug therapies and LRRK2 kinase inhibitors are in development. Prevalence of the p.G2019S has a variable ethnic and geographic distribution, the highest was reported among Ashkenazi Jews (30% in patients with familial PD, 14% in sporadic PD, 2.0% in controls) and North African Berbers (37% in patients with familial PD, 41% in sporadic PD, and 1% in controls). Little is known about the frequency of the LRRK2 p.G2019S among populations in Sub Saharan Africa. Our group and others previously reported that the p.G2019S is absent in a small cohort from Nigerian PD patients and controls. Here we used Kompetitive Allele Specific PCR (KASP) assay to screen for the p.G2019S in a larger cohort of Black African PD patients (n =126) and healthy controls (n = 55) from Nigeria. Our analysis confirmed that all patients and controls are negative for the p.G2019S mutation. This report provides further evidence that the LRRK2 p.G2019S is not implicated in PD in black populations from Nigeria and support the notion that p.G2019S mutation originated after the early human dispersal from sub-Saharan Africa. Further studies using larger cohorts and advance sequencing technology are required to underpin the genetic causes of PD in this region.
Assessment of Simplified Blood Dose Protocols for the Estimation of the Maximum Tolerable Activity in Thyroid Cancer Patients Undergoing Radioiodine Therapy Using 124I

In high-activity radioiodine therapies for differentiated thyroid cancer, blood dosimetry has been developed to estimate the maximum tolerable activity (MTA) of 131I that can be safely administered without leading to toxic effects. The reference protocol involves a series of both blood sampling (BS) and whole-body counting (WC) over a period of several days. The aim of this retrospective study was to identify simplified protocols without an appreciable loss of accuracy. Methods: Data from 211 thyroid cancer patients who received 124I blood dosimetries were retrospectively analyzed. BS and WC acquired at approximately 1–2, 4, 24, 48, and 96 h or longer after 124I administration were included. This dataset was used to determine the reference MTA and estimations based on a reduced number of combined data from BS and respective WC. MTA estimates were also determined on the basis of either BS or WC alone using some simplifying assumptions in the dosimetry approach. A simplified protocol was considered equivalent to the reference protocol if the estimates of 95% of the MTAs were within the ±20% range and the absolute maximum percentage deviation did not exceed the limit of 30% in a few cases. Lin’s concordance correlation analysis was applied to assess the protocol’s agreements. Results: Two equivalent protocols were identified that included both BS and respective WC acquired at only 3 time points (1–2, 24 or 48, and ≥96 h). Further equivalent protocols with only 3 blood samples drawn at similar time points were discovered for patients, who had undergone at least 1 radioiodine therapy. For all equivalent protocols, deviations of the mean absolute percentage MTA were below 9% and Lin’s concordance correlation coefficients of 0.95 or greater were found, indicating almost excellent agreement (according to Partik’s criteria). Conclusion: The pretherapy blood dosimetry protocol can be substantially shortened and may be beneficial to patients and patient management while reducing the radiation exposure to medical staff.
An appeal to medical journal editors: the need for a full description of laboratory methods and specimen handling in clinical study reports

1. For commercial diagnostic tests, authors must include the actual name and generation of assay, the manufacturer, and the instrument used for analyses. 2. Authors must report performance characteristics such as the imprecision of the assay in the investigators’ laboratories, the assay reportable range, and any reference (normal) range used in the study. 3. Authors must clearly indicate the types of specimens analyzed and the storage conditions for these specimens.
Breast Milk Macronutrient Components in Prolonged Lactation

Human milk (HM) is the first dietary exposure in infancy and the best nutritional option for growth and healthy development of the newborn and infant. The concentrations of macronutrients, namely proteins, carbohydrates and lipids, change during lactation stages. HM has been studied extensively in the first 6 months of lactation, but there are limited data regarding milk composition beyond 1 or 2 years postpartum. The aim of our study was to describe longitudinal changes in HM macronutrient concentrations during the prolonged lactation of healthy mothers from the 1st to the 48th month. For the macronutrient content of milk of mothers breastfeeding for longer than 18 months, fat and protein increased and carbohydrates decreased significantly, compared with milk expressed by women breastfeeding up to 12 months. Moreover, the concentration of fat, protein and carbohydrates in HM over 2 years of lactation from the 24th to the 48th month remained at a stable level. However, analyzed macronutrients were positively (carbohydrate, r = 0.51) or negatively (fat, r = −0.36 and protein, r = −0.58) correlated with the amount of feeding. Our results create a greater potential for understanding the nutritional contribution of HM over 2 years of lactation and showed that the source of calories in breast milk for older children is mainly fat, while carbohydrates play a greater role in infant nutrition in the early stage. The observed changes of macronutrient concentrations from the 1st to the 48th month of lactation are probably related to the adaptation of milk composition to the increased energy demand of the intensively growing child.
Barriers to and Facilitators of Compliance with Clinic-Based Cervical Cancer Screening: Population-Based Cohort Study of Women Aged 23-60 Years

Objective This study aims to identify possible barriers to and facilitators of cervical cancer screening by (a) estimating time and travel costs and other direct non-medical costs incurred in attending clinic-based cervical cancer screening, (b) investigating screening compliance and reasons for noncompliance, (c) determining women’s knowledge of human papillomavirus (HPV), its relationship to cervical cancer, and HPV and cervical cancer prevention, and (d) investigating correlates of HPV knowledge and screening compliance. Materials and Methods 1510 women attending the clinic-based cervical cancer screening program in Stockholm, Sweden were included. Data on sociodemographic characteristics, time and travel costs and other direct non-medical costs incurred in attending (e.g., indirect cost of time needed for the screening visit, transportation costs, child care costs, etc.), mode(s) of travel, time, distance, companion’s attendance, HPV knowledge, and screening compliance were obtained via self-administered questionnaire. Results Few respondents had low socioeconomic status. Mean total time and travel costs and direct non-medical cost per attendance, including companion (if any) were €55.6. Over half (53%) of the respondents took time off work to attend screening (mean time 147 minutes). A large portion (44%) of the respondents were noncompliant (i.e., did not attend screening within 1 year of the initial invitation), 51% of whom stated difficulties in taking time off work. 64% of all respondents knew that HPV vaccination was available; only 34% knew it was important to continue to attend screening following vaccination. Age, education, and income were the most important correlates of HPV knowledge and compliance; and additional factors associated with compliance were time off work, accompanying companion and HPV knowledge. Conclusion Time and travel costs and other direct non-medical costs for clinic-based screening can be considerable, may affect the cost-effectiveness of a screening program, and may constitute barriers to screening while HPV knowledge may facilitate compliance with screening.
Is the increase of hypomanic stages during adolescence related to gender and developmental tasks?

Abstract Objectives. To detach themselves from their family of origin, adolescents need to develop proactive behaviour which includes increased risk-taking and novelty seeking. These behaviours may be attributable both to developmental issues and to hypomanic-like stages. Since there is a lack of research focusing on hypomania in adolescents the aim of the study was to compare hypomania scores of adolescents with those of adult outpatients suffering from bipolar II disorders, and to investigate possible gender-related differences. Methods. One hundred and seven adolescents (mean age: 18 years) took part in the study; 60 of them indicated that they experienced intense romantic love; 47 were controls. Participants completed the Hypomania Check List, and data were compared with those of adult outpatients suffering from bipolar II disorders. Results. Scores of adolescents in early-stage intense romantic love differed from those of adolescent controls, but not from those of outpatients suffering from a bipolar II disorder. Factor analyses revealed that both groups of adolescents displayed higher scores for the factor “irritable/risk-taking” hypomania. A gender-related pattern was found, with increased scores for female adolescents. Conclusion. Adolescents’ developmental tasks surrounding experiences in social, psychosexual and substance use-related engagement may lead to temporary and gender-related hypomanic-like stages.
Therapeutic Effects of Horseback Riding Interventions: A Systematic Review and Meta-analysis

Objective Equine-assisted therapies, such as therapeutic riding and hippotherapy, are believed to have positive physical and emotional effects in individuals with neuromotor, developmental, and physical disabilities. The purpose of this review was to determine whether therapeutic riding and hippotherapy improve balance, motor function, gait, muscle symmetry, pelvic movement, psychosocial parameters, and the patients' overall quality of life. Design In this study, a literature search was conducted on MEDLINE, CINAHL, MBASE, SportDiscus, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, PEDro, DARE, Google Scholar, and Dissertation Abstracts. Only studies with a control/comparison group or self-controlled studies performing preintervention and postintervention assessment were included. Excluded were (1) studies not providing data on baseline score or end-point outcome, (2) single-subject studies, (3) studies providing only qualitative data, and (4) studies that used a mechanical horse. Sixteen trials were included. The methodologic quality of each study was evaluated using Downs and Black quality assessment tool. Results Most of the studies showed a trend toward a beneficial effect of therapeutic riding and hippotherapy on balance and gross motor function. The meta-analysis showed improvement in both the Berg Balance Scale and the Gross Motor Function Measure in therapeutic riding and hippotherapy programs. Conclusion Programs such as therapeutic riding and hippotherapy are a viable intervention option for patients with balance, gait, and psychomotor disorders.
Atrial Fibrosis by Late Gadolinium Enhancement Magnetic Resonance Imaging and Catheter Ablation of Atrial Fibrillation: 5‐Year Follow‐Up Data

Background Late gadolinium enhancement magnetic resonance imaging is an effective tool for assessment of atrial fibrosis. The degree of left atrial fibrosis is a good predictor of atrial fibrillation (AF) ablation success at 1 year, but the association between left atrial fibrosis and long‐term ablation success has not been studied. Methods and Results Late gadolinium enhancement magnetic resonance images of sufficient quality to quantify atrial fibrosis were obtained before the first AF ablation in 308 consecutive patients. Left atrial fibrosis was classified in 4 Utah stages (I, 0–10%; II, 10–20%; III, 20–30%; and IV, >30%). Patients were followed up for up to 5 years until the time of first arrhythmia recurrence or second ablation. A total of 308 patients were included; the mean age was 64.5±12.1 years, and 63.4% were men. During follow‐up, 157 patients experienced an arrhythmia recurrence and 106 patients underwent a repeated ablation. A graded effect was observed in which patients with more advanced atrial fibrosis were more likely to experience recurrent AF (hazard ratio for stage IV versus stage I, 2.73; 95% confidence interval, 1.57–4.75) and undergo a repeated ablation (proportional odds ratio for stage IV versus stage I, 5.19; 95% confidence interval, 2.12–12.69). Conclusions The degree of left atrial fibrosis predicts the success of AF ablation at up to 5 years follow‐up. In patients with advanced atrial fibrosis, AF ablation is associated with a high procedural failure rate.
Impact of Donor Obesity on Outcomes After Orthotopic Heart Transplantation

Background The impact of donor obesity on the outcome of orthotopic heart transplantation has not been studied. The aim of this study was to investigate the impact of donor obesity on the outcomes of adult orthotopic heart transplantation recipients. Methods and Results Data were obtained from the United Network for Organ Sharing database. All adult (age ≥18 years) patients undergoing orthotopic heart transplantation from 2000 through 2016 were included (n=31 920). We stratified the cohort by donor body mass index (BMI); 13 015 patients (40.8%) received a heart from a normal‐weight donor (BMI 18.5–24.9), 11 271 patients (35.3%) received a heart from an overweight donor (BMI 25.0–29.9), 4910 patients (15.4%) received a heart from an obese donor (BMI 30.0–34.9), and 2724 patients (8.5%) received a heart from an extremely obese donor (BMI ≥35). The cohort of obese donors was older, included a higher incidence of diabetes mellitus, and had a higher creatinine. Our data also showed that the recipients of obese donor grafts were older, had a higher BMI, creatinine, percentage of diabetes mellitus, and longer total waiting period. There was no significant difference detected in the survival likelihood (P=0.08) of patients based on a donor's BMI‐based categorized cohort. There were no significant differences found in the overall survival probability among 4 groups in the adjusted survival analyses (P=0.25). Conclusions This study demonstrated that patients receiving higher BMI donor hearts might not be subjected to an increased risk of death, at least during the short term after transplant, compared with those using the normal‐weight donors.
CT findings in pulmonary alveolar proteinosis: serial changes and prognostic implications.

Background Pulmonary alveolar proteinosis (PAP) is a rare disease of unknown origin, characterized by impaired surfactant metabolism. In some patients, residual disease is observed after treatment; notably, this may progress to end-stage pulmonary fibrosis. This study was performed to evaluate changes in lung abnormalities on serial CT scans performed on the lungs of patients diagnosed with PAP, as well as to identify factors that can be used to predict clinical improvement in PAP. Methods Twenty-five patients (16 men, nine women) were diagnosed with PAP at a single tertiary hospital. The extent and distribution of PAP were assessed on baseline and follow-up CT scans (median, 38 months; range, 2-96 months). Serial CT scans and clinical findings were analyzed to identify the predictive factors for clinical improvement in PAP. Results Baseline CT scans of patients diagnosed with PAP revealed that ground-glass opacity was the most common abnormality (100%); the second most common abnormality was interlobular/intralobular septal thickening (88%). Importantly, the final follow-up CT scans showed that the extent of lung abnormalities had decreased (n=13), including complete resolution (n=5), unchanged (n=9), and increased (n=3). Traction bronchiectasis and architectural distortion were detected in two patients (8%). On univariate and multivariate analyses, the change in the overall extent of lung abnormalities was a predictive factor for clinical improvement in PAP (odds ratio: 55.780; P=0.038). Conclusions Most patients with PAP exhibited residual disease; however, progression to pulmonary fibrosis was rare. Analyses of overall changes, with respect to lung abnormalities on serial CT scans, may be predictive of the extent of clinical improvement in given patient.
Rethinking research reproducibility

“To boldly go where no man has gone before”! Exploring and innovating—isn't this why we are in science after all? But as exciting this may be, others must be able to confirm our results through competent replication. As Karl Popper famously put it: “Single occurrences that cannot be reproduced are of no significance to science” (Popper, ). However, despite its status as a founding principle of modern science, replication is often viewed as pedestrian and unoriginal. Academia rewards the explorer, not the replicator. Not surprisingly, the current biomedical literature is dominated by exploration, but results are rarely confirmed. But how many of our discoveries are robust and will hold up if others try to reproduce them?
Long-term outcomes of persons with Lyme disease.

CONTEXT Few data exist about the long-term outcomes of patients with Lyme disease. OBJECTIVE To assess the long-term outcomes of patients with Lyme disease. DESIGN Two-part project including a community-based longitudinal cohort study and a matched cohort study. SETTING AND PARTICIPANTS Six hundred seventy-eight patients identified from a random sample of all reports of Connecticut residents with suspected Lyme disease submitted to the Connecticut Department of Public Health from 1984-1991 were evaluated in the longitudinal study; for a random subsample of 212 patients from the larger study, 212 age-matched controls without Lyme disease also were enrolled. MAIN OUTCOME MEASURES Self-reports or parents' reports of symptoms and ability to perform certain daily activities since diagnosis of Lyme disease; scores on the 36-Item Short-Form Health Survey and the Center for Epidemiologic Studies-Depression scale, for adults, by case-definition status and between patients and controls. RESULTS Of the 678 patients, 51.6% were female, 34.4% were children, and 64.3% met the national surveillance case definition for Lyme disease. Most patients (85.6%) were treated with antimicrobial agents. Interviews were conducted a median of 51 months after diagnosis (range, 15-135 months). An increased frequency of symptoms (eg, pain, fatigue) or of difficulty with daily activities (eg, performing housework, exercising) was reported by 69% of the patients, although few (19%) of these problems were attributed to Lyme disease. Whenever there was a statistically significant difference in the frequencies of either increased symptoms or increased difficulties with typical activities between those who did or did not meet the surveillance case definition, in all instances the greater frequency of problems was in the group that did not meet the case definition. The frequencies of reports of both increased symptoms and increased difficulties with typical activities among patients who had been diagnosed as having Lyme disease were similar to those among age-matched controls without Lyme disease. CONCLUSIONS In this cohort, although many patients reported increases in symptoms and/or increased difficulties with typical daily activities between 1 and 11 years after diagnosis of Lyme disease, the frequencies of these reports were similar to the frequencies of such reports among age-matched controls without Lyme disease.
High-Throughput In Vivo Analysis of Gene Expression in Caenorhabditis elegans

Using DNA sequences 5′ to open reading frames, we have constructed green fluorescent protein (GFP) fusions and generated spatial and temporal tissue expression profiles for 1,886 specific genes in the nematode Caenorhabditis elegans. This effort encompasses about 10% of all genes identified in this organism. GFP-expressing wild-type animals were analyzed at each stage of development from embryo to adult. We have identified 5′ DNA regions regulating expression at all developmental stages and in 38 different cell and tissue types in this organism. Among the regulatory regions identified are sequences that regulate expression in all cells, in specific tissues, in combinations of tissues, and in single cells. Most of the genes we have examined in C. elegans have human orthologs. All the images and expression pattern data generated by this project are available at WormAtlas (http://gfpweb.aecom.yu.edu/index) and through WormBase (http://www.wormbase.org).
Efficacy and cost-effectiveness analysis of external beam and stereotactic body radiation therapy in the treatment of spine metastases: a matched-pair analysis.

OBJECT The objective of this study was to compare the palliative efficacy and cost effectiveness of external beam radiation therapy (EBRT) to stereotactic body radiation therapy (SBRT) as primary treatment for bone metastatic disease of the spinal column. METHODS Forty-four patients were matched based on age, primary tumor site, year of treatment, and location of metastasis. Outcomes of interest were pain relief, cost-effectiveness, toxicities, and need for further intervention. Pain relief was rated as excellent, good, fair, or poor, using a radiosurgical pain scale to combine visual analog scale and verbal descriptor ordinal scale scores. Medicare fee schedules were used to compute the charges for both the technical and professional components of care. Patients in the EBRT group were treated using a linear accelerator while patients in the SBRT group were treated with the CyberKnife robotic radiosurgery system. Patients received regular follow-up evaluations by a radiation oncologist and neurosurgeon. RESULTS Forty-four patients (22 pairs) were analyzed. At a follow-up of 1 month, there was no statistically significant difference in pain between the 2 groups (p = 0.11). Patients who underwent SBRT had the highest total gross charge; depending on technique, EBRT treatments ranged from 29% to 71% of the SBRT charge. Patients treated using EBRT had more acute toxicities, and more of these patients underwent further intervention at the treated spinal level. There were no late complications attributed to either treatment modality. CONCLUSIONS External beam radiation therapy remains an efficacious and cost-effective method of palliation of spine metastases. In this study, patients treated with EBRT had more acute toxicities and were more likely to require additional interventions at the treated sites. Stereotactic body radiation therapy, although more costly, resulted in comparable rates of pain relief and late treatment-related toxicity, and continues to show promise as an emerging modality for selected patients with spine metastases.