Miracle-dz/UniFAR-FTUs huggingface dataset:
Serum glial fibrillary acidic protein correlates with multiple sclerosis disease severity

Background: Cerebrospinal fluid (CSF) levels of two soluble biomarkers, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL), have been shown to associate with multiple sclerosis (MS) disease progression. Now, both biomarkers can be detected reliably in serum, and importantly, their serum levels correlate well with their CSF levels. Objective: To evaluate the usability of serum GFAP measurement as a biomarker of progressive disease and disease severity in MS. Methods: Clinical course, Expanded Disability Status Scale (EDSS), disease duration, patient age and magnetic resonance imaging (MRI) parameters were reviewed in 79 MS patients in this cross-sectional hospital-based study. Serum samples were collected for measurement of GFAP and NfL concentrations using single molecule array (Simoa) assay. A cohort of healthy controls was evaluated for comparison. Results: Higher serum concentrations of both GFAP and NfL were associated with higher EDSS, older age, longer disease duration, progressive disease course and MRI pathology. Conclusion: Earlier studies have demonstrated that GFAP, unlike NfL, is not increased in association with acute focal inflammation-related nervous system damage. Our work suggests that GFAP serum level associates with disease progression in MS and could potentially serve as an easily measurable biomarker of central nervous system (CNS) pathology related to disease progression in MS.
Assessment of Cardiovascular Risk Factors in the Healthy Elderly.

Abstract The number and percentage of the elderly are increasing yearly, yet little has been published about the healthy elderly. Recognizing this concern the present study described cardiovascular risk factors (measured by lipid/lipoprotein profile, blood pressure, and lifestyle behaviors) in 57 white, healthy, elderly volunteers. This study found that mean values for total cholesterol and low density lipoprotein cholesterol (LDL-C) were in the borderline area of risk for cardiovascular disease according to the National Cholesterol Education Program guidelines. Mean value for high density lipoprotein cholesterol (HDL-C) was significantly higher in females. Mean diastolic blood pressure was significantly lower in females, while systolic blood pressure increased with age. Within the research group, cardiovascular risk increased with age and was higher in males than in females; however, the average relative risk for the sample was less than 1.0. The reported lifestyle habits of the healthy elderly were quit.
The Risk of Malignancy in Korean Patients with Rheumatoid Arthritis

PURPOSE To investigate the overall cancer risk and risk for specific cancers in rheumatoid arthritis (RA) patients in Korea by comparing cancer incidence between RA patients and the general population. MATERIALS AND METHODS Individuals diagnosed with RA between 1996 and 2009 who underwent treatment at the Daegu Catholic University Medical Center were retrospectively examined. 1885 patients with RA were included in the analyses. Occurrence of cancer and death during follow up was ascertained by linking medical records to the Korean Central Cancer Registry and national death certificates. For comparing cancer incidence between RA patients and general population, standardized incidence ratios (SIR) were calculated. The 95% confidence intervals (CIs) of SIRs were calculated using the shortcut method introduced by Vandenbroucke. RESULTS The total follow-up time was 10218.9 person-years. During follow up, 100 patients (31 men and 69 women) were diagnosed with cancer. Both men and women had greater risks of having malignancy, although cancer risk was greater in men. Men showed increased risks of lung cancer (SIR=5.46, 95% CI: 2.60-9.36) and leukemia (SIR=16.7, 95% CI: 1.58-47.9). Women showed increased risks of thyroid cancer (SIR=1.75, 95% CI: 1.02-2.68), cervical cancer (SIR=3.65, 95% CI: 1.65-6.42), non-Hodgkin's lymphoma (SIR=6.47, 95% CI: 2.04-13.4), and gallbladder cancer (SIR=3.87, 95% CI: 1.01-8.60). Disease-modifying anti-rheumatic drugs usage and cancer were not related: the relative risks of developing malignancy were not elevated for each medicine. CONCLUSION The overall cancer incidence was increased in Korean men and women with RA. Increased risk of specific malignancy differed according to sex.
Comparative genomics of Rhizophagus irregularis, R. cerebriforme, R. diaphanus and Gigaspora rosea highlights specific genetic features in Glomeromycotina.

Glomeromycotina is a lineage of early diverging fungi that establish arbuscular mycorrhizal (AM) symbiosis with land plants. Despite their major ecological role, the genetic basis of their obligate mutualism remains largely unknown, hindering our understanding of their evolution and biology. We compared the genomes of Glomerales (Rhizophagus irregularis, Rhizophagus diaphanus, Rhizophagus cerebriforme) and Diversisporales (Gigaspora rosea) species, together with those of saprotrophic Mucoromycota, to identify gene families and processes associated with these lineages and to understand the molecular underpinning of their symbiotic lifestyle. Genomic features in Glomeromycotina appear to be very similar with a very high content in transposons and protein-coding genes, extensive duplications of protein kinase genes, and loss of genes coding for lignocellulose degradation, thiamin biosynthesis and cytosolic fatty acid synthase. Most symbiosis-related genes in R. irregularis and G. rosea are specific to Glomeromycotina. We also confirmed that the present species have a homokaryotic genome organisation. The high interspecific diversity of Glomeromycotina gene repertoires, affecting all known protein domains, as well as symbiosis-related orphan genes, may explain the known adaptation of Glomeromycotina to a wide range of environmental settings. Our findings contribute to an increasingly detailed portrait of genomic features defining the biology of AM fungi.
Mendelian Randomization Analysis of Hemoglobin A1c as a Risk Factor for Coronary Artery Disease

OBJECTIVE Observational studies show that higher hemoglobin A1c (A1C) predicts coronary artery disease (CAD). It remains unclear whether this association is driven entirely by glycemia. We used Mendelian randomization (MR) to test whether A1C is causally associated with CAD through glycemic and/or nonglycemic factors. RESEARCH DESIGN AND METHODS To examine the association of A1C with CAD, we selected 50 A1C-associated variants (log10 Bayes factor ≥6) from an A1C genome-wide association study (GWAS; n = 159,940) and performed an inverse-variance weighted average of variant-specific causal estimates from CAD GWAS data (CARDIoGRAMplusC4D; 60,801 CAD case subjects/123,504 control subjects). We then replicated results in UK Biobank (18,915 CAD case subjects/455,971 control subjects) and meta-analyzed all results. Next, we conducted analyses using two subsets of variants, 16 variants associated with glycemic measures (fasting or 2-h glucose) and 20 variants associated with erythrocyte indices (e.g., hemoglobin [Hb]) but not glycemic measures. In additional MR analyses, we tested the association of Hb with A1C and CAD. RESULTS Genetically increased A1C was associated with higher CAD risk (odds ratio [OR] 1.61 [95% CI 1.40, 1.84] per %-unit, P = 6.9 × 10−12). Higher A1C was associated with increased CAD risk when using only glycemic variants (OR 2.23 [1.73, 2.89], P = 1.0 × 10−9) and when using only erythrocytic variants (OR 1.30 [1.08, 1.57], P = 0.006). Genetically decreased Hb, with concomitantly decreased mean corpuscular volume, was associated with higher A1C (0.30 [0.27, 0.33] %-unit, P = 2.9 × 10−6) per g/dL and higher CAD risk (OR 1.19 [1.04, 1.37], P = 0.02). CONCLUSIONS Genetic evidence supports a causal link between higher A1C and higher CAD risk. This relationship is driven not only by glycemic but also by erythrocytic, glycemia-independent factors.
Drug‐Induced Liver Injury due to Flucloxacillin: Relevance of Multiple Human Leukocyte Antigen Alleles

Some patients prescribed flucloxacillin (~ 0.01%) develop drug‐induced liver injury (DILI). HLA‐B*57:01 is an established genetic risk factor for flucloxacillin DILI. To consolidate this finding, identify additional genetic factors, and assess relevance of risk factors for flucloxacillin DILI in relation to DILI due to other penicillins, we performed a genomewide association study involving 197 flucloxacillin DILI cases and 6,835 controls. We imputed single‐nucleotide polymorphism and human leukocyte antigen (HLA) genotypes. HLA‐B*57:01 was the major risk factor (allelic odds ratio (OR) = 36.62; P = 2.67 × 10−97). HLA‐B*57:03 also showed an association (OR = 79.21; P = 1.2 × 10−6). Within the HLA‐B protein sequence, imputation showed valine97, common to HLA‐B*57:01 and HLA‐B*57:03, had the largest effect (OR = 38.1; P = 9.7 × 10−97). We found no HLA‐B*57 association with DILI due to other isoxazolyl penicillins (n = 6) or amoxicillin (n = 15) and no significant non‐HLA signals for any penicillin‐related DILI.
Outcomes in Patients With Metastatic Pancreatic Adenocarcinoma With the Introduction of New Chemotherapeutic Drugs: 10-Year Experience of a Single NCI-designated Comprehensive Cancer Center

Objectives: Adenocarcinoma of the pancreas represents the third leading cause of cancer-related death in the United States. Drug combinations, FOLFIRINOX (5-FU, leucovorin, irinotecan, and oxaliplatin) and gemcitabine/nab-paclitaxel, showed a clinically meaningful benefit when compared with single-agent gemcitabine in phase III trials. The goal of this study was to investigate whether there was an increase in overall survival (OS) for patients treated for metastatic pancreatic cancer after the introduction of the above regimens. Materials and Methods: Patients were grouped into 2 treatment eras that were before and after the introduction of these newer chemotherapeutic regimens; 2006-2010 and 2011-2015, respectively. Baseline demographics and disease-related variables were collected from metastatic pancreatic cancer treated at the Barbara Ann Karmanos Cancer Institute in Detroit, MI. Results: When stratified by treatment era, the later era had an improvement in survival (hazard ratio for death of 0.61; P=0.005). Median OS was 8.97 and 9.95 months for the earlier (n=59) versus latter era (n=99), respectively. There was an increase from 28.3% to 38.9% at 12 months between the earlier and later era, an improvement of 37.4%. African Americans had a worse outcome with a hazard ratio of 1.63 (P=0.02) for death. When comparing the eras, Caucasians had a longer median OS in each era in addition to having a greater improvement in median OS between eras. Conclusions: There was a modest improvement in median OS between 2006-2010 and 2011-2015 with the introduction of newer chemotherapeutic regimens. However, there has been no significant improvement in outcomes for African Americans or in short-term survival.
Mathematical skills and working memory profile of children with borderline intellectual functioning

Borderline intellectual functioning is a neurodevelopmental condition characterized by an intelligence quotient (IQ) in the range of 70–85. The present study aimed to investigate the mathematical abilities and the working memory of students with borderline intellectual functioning (BIF). The sample group included 10 year-old students with BIF (n = 85) and with average non-verbal IQ (n = 45). The children were assessed in non-verbal intelligence, numerical ability and working memory. Our results showed an impairment of mathematical skills, especially in the operation tasks, and working memory in children with BIF, compared to typically developing peers. Generally, their skills seemed to be consistent with intelligence scores (WOND and AWMA scores ≥ 70). In some cases, children with BIF could have mathematical difficulties (WOND < 70). In general, they showed visuospatial short-term memory and central executive subsystem more damaged than non-verbal intelligence while the verbal short-term memory was similar to the IQ.
Pengembangan Lembar Kegiatan Peserta Didik Berbasis Inkuiri Terbimbing Pada Materi Termokimia Kelas XI SMA/MA

Penelitian pengembangan ini bertujuan untuk mengetahui: (1) has il tiap tahapan pengembangan LKPD berbas is inkuiri terbimbing pada materi Termokimia , (2) kelayakan LKPD berbas is inkuiri terbimbing pada pembelajaran termokimia, (3) efektivitas LKPD berbas is inkuiri terbimbing pada pembelajaran termokimia ditinjau dari has il belajar pes erta didik. Penelitian dan pengembangan LKPD menggunakan pros edur R&D Borg and Gall yang dis ederhanakan menjadi 9 tahapan . Berdas arkan has il analis is data, dapat dis impulkan: (1) Has il s etiap tahapan pengembangan produk melalui pros edur penelitian dan pengembangan (R&D) Borg and Gall adalah ters us unnya LKPD berbas is inkuiri terbimbing pada materi Termokimia yang telah direvis i berdas arkan s aran dan mas ukan dari validator s erta telah diujicobakan kepada guru dan pes erta didik pada tahap uji coba lapangan awal, uji coba lapangan ut ama, dan uji coba lapangan operas ional. (2) LKPD berbas is inkuiri terbimbing pada materi termokimia yang telah dikembangkan layak digunakan untuk pembelajaran berdas arkan penilaian dari ahli materi, ahli media, ahli bahas a,dan ahli pembelajaran dengan rata-rata perolehan nilai VAiken lebih dari 0,80, penilaian dari guru dengan pers entas e s kor 87,04%, dan penilaian dari pes erta didik dengan pers entas e s kor 84,07% yang menunjukkan katagori “Sangat Baik”, (3) LKPD berbas is inkuiri terbimbing pada materi termokimia efektif meningkatkan has il belajar pes erta didik. Rata-rata nilai has il belajar pes erta didik yang belajar menggunakan LKPD berbas is inkuiri terbimbing pada materi termokimia yang dikembangkan lebih tinggi dibandingkan rata -rata nilai has il belajar pes erta didik yang tidak belajar menggunakan LKPD berbas is inkuiri terbimbing.
Wafer-scale transferred multilayer MoS2 for high performance field effect transistors

Chemical vapor deposition synthesis of semiconducting transition metal dichalcogenides (TMDs) offers a new route to build next-generation semiconductor devices. But realization of continuous and uniform multilayer (ML) TMD films is still limited by their specific growth kinetics, such as the competition between surface and interfacial energy. In this work, a layer-by-layer vacuum stacking transfer method is applied to obtain uniform and non-destructive ML-MoS2 films. Back-gated field effect transistor (FET) arrays of 1L- and 2L-MoS2 are fabricated on the same wafer, and their electrical performances are compared. We observe a significant increase of field-effect mobility for 2L-MoS2 FETs, up to 32.5 cm2 V−1 s−1, which is seven times higher than that of 1L-MoS2 (4.5 cm2 V−1 s−1). Then we also fabricated 1L-, 2L-, 3L-, and 4L-MoS2 FETs to further investigate the thickness-dependent characteristics of transferred ML-MoS2. Measurement results show a higher mobility but a smaller current on/off ratio as the layer number increases, suggesting that a balance between mobility and current on/off ratio can be achieved in 2L- and 3L-MoS2 FETs. Dual-gated structure is also investigated to demonstrate an improved electrostatic control of the ML-MoS2 channel.
Development challenges and opportunities in aerosol drug delivery systems in non-invasive ventilation in adults

ABSTRACT Introduction: With the gain in popularity of non-invasive ventilation (NIV), particularly in patients requiring drug delivery by aerosol therapy, the feasibility of the combination between NIV and aerosol therapy has regularly been questioned. Areas covered: This review covers the in vitro and in vivo studies which explored the effects of this combination on pulmonary drug delivery (imaging and pharmacological studies) and on physiological measurements. Expert opinion: Even if the feasibility of the combination is evident, the type of nebulizer influences the lung deposition with a greater delivery with vibrating mesh nebulizers. The influence of the interfaces of NIV devices should be further investigated even if vented masks may seem less efficient for nebulization. There is also a need to develop new devices and modalities, or specific components better designed for a more efficient delivery, to offer more optimal particles size to lung delivery. The use of spacer also seems promising to improve the lung delivery even if strong evidences are still missing. Finally, it would be interesting to explore the influence of all spontaneous modes which use different flow-time curves. Further investigations should focus on the synchronization of the delivery with the inspiratory part of the respiratory cycle in patients during NIV, particularly when delivering toxic or expensive drugs.
Varroa destructor feeds primarily on honey bee fat body tissue and not hemolymph

Significance Varroa destructor causes considerable damage to honey bees and subsequently the field of apiculture through just one process: feeding. For five decades, we have believed that these mites consume hemolymph like a tick consumes blood, and that Varroa cause harm primarily by vectoring viruses. Our work shows that they cause damage more directly. Varroa externally digest and consume fat body tissue rather than blood. These findings explain the failure of some previous attempts at developing effectively targeted treatment strategies for Varroa control. Furthermore, it provides some explanation for the diverse array of debilitating pathologies associated with Varroa that were unexplained by hemolymph removal alone. Our work provides a path forward for the development of novel treatment strategies for Varroa. The parasitic mite Varroa destructor is the greatest single driver of the global honey bee health decline. Better understanding of the association of this parasite and its host is critical to developing sustainable management practices. Our work shows that this parasite is not consuming hemolymph, as has been the accepted view, but damages host bees by consuming fat body, a tissue roughly analogous to the mammalian liver. Both hemolymph and fat body in honey bees were marked with fluorescent biostains. The fluorescence profile in the guts of mites allowed to feed on these bees was very different from that of the hemolymph of the host bee but consistently matched the fluorescence profile unique to the fat body. Via transmission electron microscopy, we observed externally digested fat body tissue in the wounds of parasitized bees. Mites in their reproductive phase were then fed a diet composed of one or both tissues. Mites fed hemolymph showed fitness metrics no different from the starved control. Mites fed fat body survived longer and produced more eggs than those fed hemolymph, suggesting that fat body is integral to their diet when feeding on brood as well. Collectively, these findings strongly suggest that Varroa are exploiting the fat body as their primary source of sustenance: a tissue integral to proper immune function, pesticide detoxification, overwinter survival, and several other essential processes in healthy bees. These findings underscore a need to revisit our understanding of this parasite and its impacts, both direct and indirect, on honey bee health.
Biocompatible Polymer Nanoparticles for Drug Delivery Applications in Cancer and Neurodegenerative Disorder Therapies

Polymer nanoparticles (NPs) represent one of the most innovative non-invasive approaches for drug delivery applications. NPs main objective is to convey the therapeutic molecule be they drugs, proteins, or nucleic acids directly into the target organ or tissue. Many polymers are used for the synthesis of NPs and among the currently most employed materials several biocompatible synthetic polymers, namely polylactic acid (PLA), poly lactic-co-glycolic acid (PLGA), and polyethylene glycol (PEG), can be cited. These molecules are made of simple monomers which are naturally present in the body and therefore easily excreted without being toxic. The present review addresses the different approaches that are most commonly adopted to synthetize biocompatible NPs to date, as well as the experimental strategies designed to load them with therapeutic agents. In fact, drugs may be internalized in the NPs or physically dispersed therein. In this paper the various types of biodegradable polymer NPs will be discussed with emphasis on their applications in drug delivery. Close attention will be devoted to the treatment of cancer, where both active and passive targeting is used to enhance efficacy and reduce systemic toxicity, and to diseases affecting the central nervous system, inasmuch as NPs can be modified to target specific cells or cross membrane barriers.
Latent Sex Differences in Molecular Signaling That Underlies Excitatory Synaptic Potentiation in the Hippocampus

Excitatory synapses can be potentiated by chemical neuromodulators, including 17β-estradiol (E2), or patterns of synaptic activation, as in long-term potentiation (LTP). Here, we investigated kinases and calcium sources required for acute E2-induced synaptic potentiation in the hippocampus of each sex and tested whether sex differences in kinase signaling extend to LTP. We recorded EPSCs from CA1 pyramidal cells in hippocampal slices from adult rats and used specific inhibitors of kinases and calcium sources. This revealed that, although E2 potentiates synapses to the same degree in each sex, cAMP-activated protein kinase (PKA) is required to initiate potentiation only in females. In contrast, mitogen-activated protein kinase, Src tyrosine kinase, and rho-associated kinase are required for initiation in both sexes; similarly, Ca2+/calmodulin-activated kinase II is required for expression/maintenance of E2-induced potentiation in both sexes. Calcium source experiments showed that L-type calcium channels and calcium release from internal stores are both required for E2-induced potentiation in females, whereas in males, either L-type calcium channel activation or calcium release from stores is sufficient to permit potentiation. To investigate the generalizability of a sex difference in the requirement for PKA in synaptic potentiation, we tested how PKA inhibition affects LTP. This showed that, although the magnitude of both high-frequency stimulation-induced and pairing-induced LTP is the same between sexes, PKA is required for LTP in females but not males. These results demonstrate latent sex differences in mechanisms of synaptic potentiation in which distinct molecular signaling converges to common functional endpoints in males and females. SIGNIFICANCE STATEMENT Chemical- and activity-dependent neuromodulation alters synaptic strength in both male and female brains, yet few studies have compared mechanisms of neuromodulation between the sexes. Here, we studied molecular signaling that underlies estrogen-induced and activity-dependent potentiation of excitatory synapses in the hippocampus. We found that, despite similar magnitude increases in synaptic strength in males and females, the roles of cAMP-regulated protein kinase, internal calcium stores, and L-type calcium channels differ between the sexes. Therefore, latent sex differences in which the same outcome is achieved through distinct underlying mechanisms in males and females include kinase and calcium signaling involved in synaptic potentiation, demonstrating that sex is an important factor in identification of molecular targets for therapeutic development based on mechanisms of neuromodulation.