Miracle-dz/UniFAR-FTUs huggingface dataset:
ABCA7 risk variant in healthy older African Americans is associated with a functionally isolated entorhinal cortex mediating deficient generalization of prior discrimination training

Using high‐resolution resting state functional magnetic resonance imaging (fMRI), the present study tested the hypothesis that ABCA7 genetic risk differentially affects intra‐medial temporal lobe (MTL) functional connectivity between MTL subfields, versus internetwork connectivity of the MTL with the medial prefrontal cortex (mPFC), in nondemented older African Americans. Although the association of ABCA7 risk variants with Alzheimer's disease (AD) has been confirmed worldwide, its effect size on the relative odds of being diagnosed with AD is significantly higher in African Americans. However, little is known about the neural correlates of cognitive function in older African Americans and how they relate to AD risk conferred by ABCA7. In a case–control fMRI study of 36 healthy African Americans, we observed ABCA7 related impairments in behavioral generalization that was mediated by dissociation in entorhinal cortex (EC) resting state functional connectivity. Specifically, ABCA7 risk variant was associated with EC‐hippocampus hyper‐synchronization and EC‐mPFC hypo‐synchronization. Carriers of the risk genotype also had a significantly smaller anterolateral EC, despite our finding no group differences on standardized neuropsychological tests. Our findings suggest a model where impaired cortical connectivity leads to a more functionally isolated EC at rest, which translates into aberrant EC‐hippocampus hyper‐synchronization resulting in generalization deficits. While we cannot identify the exact mechanism underlying the observed alterations in EC structure and network function, considering the relevance of Aβ in ABCA7 related AD pathogenesis, the results of our study may reflect the synergistic reinforcement between amyloid and tau pathology in the EC, which significantly increases tau‐induced neuronal loss and accelerates synaptic alterations. Finally, our results add to a growing literature suggesting that generalization of learning may be a useful tool for assessing the mild cognitive deficits seen in the earliest phases of prodromal AD, even before the more commonly reported deficits in episodic memory arise.
Emergence of VIM-2-producing Citrobacter freundii in Japan

Carbapenemase-producing Enterobacteriaceae show multi-antibiotic resistance; thus, infections with these bacteria are difficult to treat, representing a growing problem worldwide. Carbapenemase is often encoded by a plasmid that spreads via conjugal transfer. In the present journal, a recent report from Zhejiang Province, China payed attention to the increasing emergence of carbapenem resistance in gram-negative bacteria [1]. In 70.4% (59/71) isolates of carbapenem-resistant Enterobacteriaceae, two carbapenemase-encoding genes were detected, namely blaKPC-2 and blaIMP-4/blaIMP-8. Among class B metallo-b-lactamases, blaVIM were detected in Pseudomonas aeruginosa but occurred in none of not 71 isolates of carbapenem-resistant strains of Enterobacteriaceae. Aiming to add information to the present increasing emergence of carbapenemase-producing gram-negatives, we here report our detection of VIM-2-producing Citrobacter freundii in Japan. A carbapenem-non-susceptible C. freundii strain (NR1374) was isolated from a Japanese hospital in 2016. The MICs were determined by agar dilution method according to Clinical and Laboratory Standards Institute (CLSI) guidelines. The isolate was resistant to all broadspectrum cephalosporins except for cefepime (Table 1). The result of the carbapenem inactivation method [2,3] was negative, whereas that of the modified carbapenem inactivation method [4] was positive. This characteristic suggests that strain NR1374 produces carbapenemase. The presence of b-lactamase genes was determined by PCR and DNA sequencing [5,6], which revealed that NR1374 carried the blaVIM-2 gene. This is the first detection of blaVIM-2 from Enterobacteriaceae in Japan. In addition, blaVIM-2 was encoded on a plasmid co-encoding the known resistance genes fosE, aacA31 and sul as gene cassettes on a class I integron structure (Genebank accession no. LC367232). This structure was also detected for a resistant plasmid in P. aeruginosa in Japan [7]; therefore, this plasmid is suspected to have been transferred from P. aeruginosa to C. freundii. To confirm the transferability of blaVIM-2, mating experiments were carried out using the sodium azideresistant Escherichia coli strain J53. Plasmid incompatibility groups were identified by the PCR-based replicon typing method [8]. The plasmid belonged to the IncW group and the transfer frequency was 1.3 10 . Although the plasmid DNA was not transferred in the mating experiment, it could be electroporated into P. aeruginosa PAO1. The transformants showed higher MIC values for all b-lactams except for cefepime, which was conferred by carrying blaVIM-2 encoded on the IncW plasmid (Table 1). The IncW plasmid has high affinity for various bacterial species, and thereby has great potential for broad spread [9]. NR1374 was determined to belong
The role of IL‐3 in bone

In the recent past, there has been a burgeoning interest in targeting cytokines such as IL‐3 for specific disease conditions of bone such as rheumatoid arthritis and multiple myeloma. Unlike other cytokines, IL‐3 is a cytokine with a multilineage potential and broad spectrum of target cells and it plays a vital role in hematopoiesis. Due to its common receptor subunit, the action of IL‐3 shows functional redundancy with other cytokines such as the granulocyte‐macrophage colony‐stimulating factor and IL‐5. IL‐3 has been successfully used in ameliorating radiation‐induced bone marrow aplasia and similar conditions. However, the role of IL‐3 in bone cells has not been fully unraveled yet; therefore, the aim of this overview is to present the effects of IL‐3 in bone with a special emphasis on osteoclasts and osteoblasts in a concise manner.
PERAN PEREMPUAN DALAM MENINGKATKAN KINERJA UMKM

Abstrak Industri UMKM di Indonesia saat ini begitu pesat, hal ini terbukti dengan sektor UMKM mampu bertahan pada saat krisis ekonomi. Disamping faktor pendidikan, munculnya persoalan perempuan tidak dapat dipisahkan dari faktor-faktor ideologi, struktural dan kultural, ketiganya saling terkait menguatkan suatu situasi yang sangat tidak menguntungkan perempuan. Peran serta wanita dalam berbagai sektor sangat tinggi, sesuai dengan kelebihan-kelebihan yang dimiliki wanita seperti tekun, teliti, ulet, sabar, jujur, tangguh, rasa tanggung jawab tinggi, kemauan keras, semangat tinggi dan disiplin. Oleh sebab itu pemerintah perlu memberikan pembinaan kepada UMKM yang dikelola perempuan dengan bantuan kredit lunak dan membekali dengan pelatihan kewirausahaan maupun manajemen sehingga UMKM yang dikelola perempuan bisa berkembang dengan baik. Kata Kunci: perempuan, usaha kecil menengah mikro
Distinct microglia profile in Creutzfeldt–Jakob disease and Alzheimer's disease is independent of disease kinetics

Activated microglia represent a common pathological feature of neurodegenerative diseases. Sporadic Creutzfeldt–Jakob disease (sCJD) patients show more pronounced microglial activation than Alzheimer's disease (AD) patients. Whether these differences are due to differences in disease kinetics or represent disease‐specific changes is unknown. We investigated microglial phenotypes in brains of rapidly progressive AD (rpAD) and sCJD patients matched for clinical presentation, including disease duration. We immunostained the frontal cortex, basal ganglia and cerebellum in 16 patients with rpAD and sCJD using antibodies against markers of microglia and recruited monocytes (ionized calcium‐binding adaptor molecule 1, human leukocyte antigen DPQR, Cluster of Differentiation 68), an antibody unique to brain‐resident microglia (transmembrane protein 119 (TMEM119)), in addition to antibodies against a marker of astrocytes (glial fibrillary acidic protein), amyloid‐β (Aβ) and pathological prion protein. rpAD patients showed a distinct microglial phenotype with a high abundance of TMEM119‐positive microglia in all investigated regions. Presence of Aβ deposits seen in a sCJD patient with concomitant deposition of Aβ led to increase of TMEM119‐positive microglia. Our data suggest that in rpAD, activation of brain‐resident microglia significantly contributes to microgliosis, whereas in sCJD the TMEM119 signature of resident microglial cells is barely detectable. This is irrespective of disease duration and may indicate disease‐specific microglial reaction.
Can community health workers manage uncomplicated severe acute malnutrition? A review of operational experiences in delivering severe acute malnutrition treatment through community health platforms

Abstract Community health workers (CHWs) play an important role in the detection and referral of children with severe acute malnutrition (SAM) in many countries. However, distance to health facilities remains a significant obstacle for caregivers to attend treatment services, resulting in SAM treatment coverage rates below 40% in most areas of intervention. The inclusion of SAM treatment into the current curative tasks of CHWs has been proposed as an approach to increase coverage. A literature review of operational experiences was conducted to identify opportunities and challenges associated with this model. A total of 18 studies providing evidence on coverage, clinical outcomes, quality of care, and/or cost‐effectiveness were identified. The studies demonstrate that CHWs can identify and treat uncomplicated cases of SAM, achieving cure rates above the minimum standards and reducing default rates to less than 8%. Although the evidence is limited, these findings suggest that early detection and treatment in the community can increase coverage of SAM in a cost‐effective manner. Adequate training and close supervision were found to be essential to ensure high‐quality performance of CHWs. Motivation through financial compensation and other incentives, which improve their social recognition, was also found to be an important factor contributing to high‐quality performance. Another common challenge affecting performance is insufficient stock of key commodities (i.e., ready‐to‐use therapeutic food). The review of the evidence ultimately demonstrates that the successful delivery of SAM treatment via CHWs will require adaptations in nutrition and health policy and practice.
Circulating concentrations of B group vitamins and urothelial cell carcinoma

B‐group vitamins, as components of the one carbon metabolism pathway, are involved in DNA synthesis, repair and methylation. Our aim was to investigate associations between circulating plasma levels of B vitamins and urothelial cell carcinoma (UCC). We conducted a nested case–control study of UCC within the Melbourne Collaborative Cohort Study. B vitamins were measured in pre‐diagnostic plasma samples. Conditional logistic regression was used to estimate odds ratios (OR) for UCC risk associated with circulating B vitamins in 363 matched cases and controls. In a case‐only analysis (N = 390), hazard ratios (HR) for overall survival associated with plasma B vitamins were estimated using Cox regression. There were no strong associations between UCC risk and pre‐diagnostic levels of plasma B vitamins. No heterogeneity in UCC risk was observed by subtype (invasive or superficial), sex, smoking status or alcohol intake. There was no heterogeneity by country of birth for most B vitamins, except for folate (p‐homogeneity = 0.03). In UCC cases, there were no strong associations between plasma B vitamins and overall survival. We found no associations between pre‐diagnostic plasma concentrations of B‐group vitamins and UCC risk or survival.
Achieving balance in the treatment and monitoring of neovascular age‐related macular degeneration in the real world: lessons from the Netherlands cohort of the AURA study

E ditor, There is growing interest in monitoring treatment patterns and outcomes associated with anti-vascular endothelial growth factor agents in real world settings. AURA was an international, retrospective observational study conducted in Canada, France, Germany, Ireland, Italy, the Netherlands, the United Kingdom (UK), and Venezuela; the design (including ethics approval), participants and global outcomes of AURA are described in detail elsewhere (Holz et al. 2015). AURA showed that visual acuity (VA) outcomes achieved following ranibizumab use in patients with neovascular agerelated macular degeneration (nAMD) were worse than those observed in clinical trials (Holz et al. 2015). These findings, which are also mirrored in some other real world studies (Rakic et al. 2013; van Asten et al. 2015), may be explained by several interacting factors, including resource patterns like the use of a loading scheme. Although the AURA data are now well established, we explored the Netherlands cohort in more detail as countryspecific data are lacking, and we wanted to examine the impact of treatment and monitoring patterns after the loading phase on VA outcome in a real world setting. Patients from the Netherlands (n = 337), UK (n = 355) and all ‘other’ cohorts (n = 1094) who received a loading scheme in AURA were analyzed. The mean baseline VA (letter score) was lower in the Netherlands (50.4) than in UK (54.3) or ‘other’ cohorts (56.8). The mean change in VA 7.61 8.32 6.82
Fetal pulmonary artery acceleration/ejection time prognostic accuracy for respiratory complications in preterm prelabor rupture of membranes

Abstract Objective: To determine the prognostic accuracy of the fetal pulmonary artery acceleration time/ejection time (PATET) for the prediction of neonatal respiratory complications (NRCs) in pregnancies with preterm premature rupture of membranes (PPROM). Methods: This is a prospective cohort of singleton pregnancies complicated by PPROM managed in our institution from October 2015 to April 2018. Inclusion criteria included mothers from 13 to 46 years of age and singleton pregnancies with PATET measurements <7 days prior to delivery. PATET was obtained by placing the Doppler caliper in the main pulmonary artery proximal to the bifurcation of this vessel. NRC was defined as: need for ventilatory support, respiratory distress syndrome (RDS), or lung hypoplasia. Logistic regression models and area under the receiver operating characteristic curves (ROC) were utilized to determine the prognostic accuracy of PATET and gestational age for NRC and RDS. Results: Of 95 patients included, 46 had NRC (RDS = 33). PATET was a significant predictor of NRC (AUC 0.74; 95%CI: 0.61–0.83; p < .001) and RDS (AUC 0.69; 95%CI: 0.57–0.80; p = .021) in PPROM. Gestational age at delivery and gestational age at PPROM were also significantly associated with NRC and RDS. Their predictive accuracy for NRC was 0.87 and 0.84, and for RDS 0.85 and 0.86, respectively. Conclusions: PATET is a statistically significant predictor for NRC in pregnancies with PPROM; however, its clinical use may be limited as gestational age is a better predictor of these outcomes. Rationale: NRCs are common in pregnancies complicated by preterm prelabor rupture of membranes (PPROM). We aim to determine the prognostic accuracy of the fetal PATET for the prediction of neonatal NRC in these pregnancies. Our results indicate that PATET is a statistically significant predictor for NRC in pregnancies with PPROM; however, its clinical use may be limited, as gestational age is a better predictor of these outcomes.
Manufacturing classification system in the real world: factors influencing manufacturing process choices for filed commercial oral solid dosage formulations, case studies from industry and considerations for continuous processing

Abstract Following the first Manufacturing Classification System (MCS) paper, the team conducted surveys to establish which active pharmaceutical ingredient (API) properties were important when selecting or modifying materials to enable an efficient and robust pharmaceutical manufacturing process. The most commonly identified factors were (1) API particle size: small particle sizes are known to increase risk of processing issues; (2) Drug loading in the formulation: high drug loadings allow less opportunity to mitigate poor API properties through the use of excipients. The next step was to establish linkages with process decisions by identifying publicly-available proxies for these important parameters: dose (in place of drug loading) and BCS class (in place of particle size). Poorly-soluble API were seen as more likely to have controlled (smaller) particle size than more highly soluble API. Analysis of 435 regulatory filings revealed that higher doses and more poorly-soluble API was associated with more complex processing routes. Replacing the proxy factors with the original parameters should give the opportunity to demonstrate stronger trends. This assumption was tested by accessing a dataset relating to commercial tablet products. This showed that, for dry processes, a larger particle size was associated with higher achievable drug loading as determined by percolation threshold.
Precipitating events in child and adolescent chronic musculoskeletal pain

Introduction: The epidemiology of chronic pain in youth has been increasingly documented over the past decade. However, the precipitating events associated with the onset of pediatric chronic pain are not well studied. Objectives: Understanding the events that precede the onset of pain, and are reported by patients as germane to the early stages of their pain, may add one piece to the puzzle of the causal etiology of pediatric chronic pain disorders. Methods: We conducted a retrospective chart review of 320 young people attending a tertiary care chronic pain clinic with musculoskeletal chronic pain. Results: Approximately two-thirds of patients reported a precipitating event for their pain; injury was the most commonly reported event, followed by a chronic disease, then an infection or illness. Surgery was the least commonly reported event. About one-third of patients did not report any precipitating event for their pain. Patients with neuropathic pain were even more likely to report a precipitating event compared to those with localized and diffuse musculoskeletal pain. Patients with localized musculoskeletal pain and neuropathic pain were most likely to report an injury, whereas patients with diffuse musculoskeletal pain were most likely to report a chronic disease. We found little to no evidence that the presence or type of precipitating event was associated with patients' psychological or physical functioning. Conclusion: This study adds to the epidemiological evidence base for pediatric chronic pain disorders.
Association Between Maternal Serum Folate Concentrations in the First Trimester and the Risk of Birth Defects: The Hokkaido Study of Environment and Children’s Health

BACKGROUND Low red blood cell folate concentrations during early pregnancy might cause neural tube defects. However, the association between folate concentrations and birth defects of other neural crest cell-derived organs remains unknown. We investigated the associations between birth defects and first-trimester serum folate concentrations in a birth-cohort study in Japan. METHODS In total, 14,896 women who were prior to 13 weeks of gestation were enrolled from 2003 through 2012. Birth defect information was obtained from medical records and questionnaires. The association between folate levels in the first trimester and birth defects categorized as ICD-10 cord defects and neural crest cell-derived organ defects was examined. The crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) per log-transformed folate concentration were calculated using logistic regression. RESULTS Blood samples were obtained at a mean of 10.8 weeks of gestation. Median serum folate level was 16.5 (interquartile range, 13.4-21.5) nmol/L, and the deficiency level (less than 6.8 nmol/L) was 0.7%. There were 358 infants with birth defects. The adjusted odds ratio for any birth defect, ventricular septal defects, and cleft lip was 0.99 (95% CI, 0.74-1.32), 0.63 (95% CI, 0.30-1.33), and 4.10 (95% CI, 0.96-17.58), respectively. There were no significant associations between first-trimester maternal serum folate and the risk of birth defects. CONCLUSIONS We were unable to demonstrate a relationship between maternal serum folate in the first trimester and birth defects. Potential confounding factors may have influenced our results.
Improvement of Energy Efficiency of Markov ACMV Systems based on PTS Information of Occupants

This study proposes a novel method of energy efficiency improvement in Air-Conditioning and Mechanical Ventilation (ACMV) systems on the basis of occupant thermal states (ComforyDiscomfort) evaluated by Predictive Thermal State (PTS) models. An ACMV Operating State (OS) algorithm is proposed and integrated with PTS models under assumptions of Markov Decision Process (MDP). The ACMV OS algorithm and the developed PTS models are applied in our thermal laboratory. The results show that NN based PTS models perform better than ELM based ones in terms of energy saving in our case studies. The optimal sampling time of the applied ACMV OS algorithm is 10 mins without the issues of system lagging and losing sharpness of tracking thermal states of occupants. The experimental results show that the proposed ACMV OS algorithm can significantly reduce around 10 kWh out of 74 kWh (about 13.5% energy saving) daily in laboratory conditions without compromising the thermal comfort level of occupants.
Enlightening chronic obstructive pulmonary disease through patients’ and caregivers’ narratives

Purpose The primary aim of this research was to raise awareness for COPD through real narratives of patients, caregivers, and pulmonologists. The second objective includes providing clinicians new means of caring for and treating patients with COPD. Methods Using narrative medicine, testimonies from patients, their caregivers, and clinicians were collected through an online questionnaire enriched by a narrative plot. Narrations were analyzed throughout descriptive statistics and an elaboration of recurring words and expressions. Results Throughout the project, 350 narratives were collected from 235 patients, 55 caregivers, and 60 physicians. Though a generally neutral reaction had been observed upon diagnosis, COPD had been found to have a high impact on the patients’ and caregivers’ lives. Metaphors utilized by patients and caregivers were suggestive of fear and panic unlike those utilized by clinicians who usually had a more technical approach. Smoking was a significant concern for not only patients and caregivers but also clinicians. Conclusion Physicians are therefore challenged to find new ways of communicating COPD to raise awareness on this pathology and encourage corrective habits. An important social objective should be the implementation of a health system that is able to optimize patients’ and caregivers’ lives.
End-to-End Supervised Lung Lobe Segmentation

The segmentation and characterization of the lung lobes are important tasks for Computer Aided Diagnosis (CAD) systems related to pulmonary disease. The detection of the fissures that divide the lung lobes is non-trivial when using classical methods that rely on anatomical information like the localization of the airways and vessels. This work presents a fully automatic and supervised approach to the problem of the segmentation of the five pulmonary lobes from a chest Computer Tomography (CT) scan using a Fully RegularizedV-Net (FRV- Net), a 3D Fully Convolutional Neural Network trained end-to- end. Our network was trained and tested in a custom dataset that we make publicly available. It can correctly separate the lobes even in cases when the fissure is not well delineated, achieving 0.93 in per-lobe Dice Coefficient and 0.85 in the inter-lobar Dice Coefficient in the test set. Both quantitative and qualitative results show that the proposed method can learn to produce correct lobe segmentations even when trained on a reduced dataset.