Miracle-dz/UniFAR-FTUs huggingface dataset:
Exploration of olfactory information processing within different components and associated structures of the olfactory system

Bislang wurde in verhaltenden Tieren die Beteiligung des olfaktorischen (piriformen) Kortexes in synaptischer Plastizitat und dessen Einfluss auf den Hippocampus (HC) nicht beschrieben. Der anteriore piriforme Kortex (APC) wurde untersucht um aufzudecken ob Vorverarbeitung von sensorischen Informationen auf verschiedenen synaptischen Ebenen im olfaktorischen System andauernde synaptische Plastizitat im APC beeinflusst. Ein direkter Einfluss des APCs auf Plastizitat im HC wurde erforscht. In Ratten wurde die Auswirkung eines breiten Frequenzspektrums von Stimulationsmustern auf synaptische Starke im APC oder Gyrus dentatus (DG) gepruft. Synaptische Plastizitat im APC ist abhangig von Top-down Kontrolle durch den orbitofrontalen Kortex oder den intrinsischen Kreislauf des APCs. Der Bulbus olfaktorius hat keinen Einfluss auf Plastizitat im APC. Der APC hat direkten Einfluss auf Kodierung von olfaktorischen Informationen im HC durch Induktion von synaptischer Plastizitat im DG.
Quality‐of‐life outcomes after operative management of primary and secondary lymphoedema: a systematic review

Lymphoedema is an incurable and progressive disease that affects not only physical function but overall quality of life. Surgical treatment options for the management of lymphoedema are being increasingly performed. This study aims to review post‐operative health‐related quality of life (HRQOL) following surgical treatment of lymphoedema.
Identification of multiple system atrophy mimicking Parkinson’s disease or progressive supranuclear palsy

Abstract We studied a subset of patients with autopsy-confirmed multiple system atrophy who presented a clinical picture that closely resembled either Parkinson’s disease or progressive supranuclear palsy. These mimics are not captured by the current diagnostic criteria for multiple system atrophy. Among 218 autopsy-proven multiple system atrophy cases reviewed, 177 (81.2%) were clinically diagnosed and pathologically confirmed as multiple system atrophy (i.e. typical cases), while the remaining 41 (18.8%) had received an alternative clinical diagnosis, including Parkinson’s disease (i.e. Parkinson’s disease mimics; n = 16) and progressive supranuclear palsy (i.e. progressive supranuclear palsy mimics; n = 17). We also reviewed the clinical records of another 105 patients with pathologically confirmed Parkinson’s disease or progressive supranuclear palsy, who had received a correct final clinical diagnosis (i.e. Parkinson’s disease, n = 35; progressive supranuclear palsy-Richardson syndrome, n = 35; and progressive supranuclear palsy-parkinsonism, n = 35). We investigated 12 red flag features that would support a diagnosis of multiple system atrophy according to the current diagnostic criteria. Compared with typical multiple system atrophy, Parkinson’s disease mimics more frequently had a good levodopa response and visual hallucinations. Vertical gaze palsy and apraxia of eyelid opening were more commonly observed in progressive supranuclear palsy mimics. Multiple logistic regression analysis revealed an increased likelihood of having multiple system atrophy [Parkinson’s disease mimic versus typical Parkinson’s disease, odds ratio (OR): 8.1; progressive supranuclear palsy mimic versus typical progressive supranuclear palsy, OR: 2.3] if a patient developed any one of seven selected red flag features in the first 10 years of disease. Severe autonomic dysfunction (orthostatic hypotension and/or urinary incontinence with the need for a urinary catheter) was more frequent in clinically atypical multiple system atrophy than other parkinsonian disorders (Parkinson’s disease mimic versus typical Parkinson’s disease, OR: 4.1; progressive supranuclear palsy mimic versus typical progressive supranuclear palsy, OR: 8.8). The atypical multiple system atrophy cases more frequently had autonomic dysfunction within 3 years of symptom onset than the pathologically confirmed patients with Parkinson’s disease or progressive supranuclear palsy (Parkinson’s disease mimic versus typical Parkinson’s disease, OR: 4.7; progressive supranuclear palsy mimic versus typical progressive supranuclear palsy, OR: 2.7). Using all included clinical features and 21 early clinical features within 3 years of symptom onset, we developed decision tree algorithms with combinations of clinical pointers to differentiate clinically atypical cases of multiple system atrophy from Parkinson’s disease or progressive supranuclear palsy.
Frailty implications for exercise participation and outcomes in patients with heart failure

Frailty is common in people with heart failure (HF) and associated with poorer outcomes. The aim of this study was to describe the characteristics, exercise participation, and outcomes of frail and not‐frail participants enrolled in a randomized trial of exercise training (ET) within a cardiac rehabilitation (CR) program.
Novel mineral regulatory pathways in ovine pregnancy: II. Calcium-binding proteins, calcium transporters, and vitamin D signaling

Abstract Mineralization of the fetal mammalian skeleton requires a hypercalcemic gradient across the placenta from mother to fetus. However, the mechanisms responsible for maintaining the placental transport of calcium remain poorly understood. This study aimed to identify calcium and vitamin D regulatory pathway components in ovine endometria and placentae across gestation. Suffolk ewes were bred with fertile rams upon detection of estrus (Day 0). On Days 9, 12, 17, 30, 70, 90, 110, and 125 of pregnancy (n=3–14/Day), ewes were euthanized and hysterectomized. Calcium abundance was influenced by gestational day in uterine flushings and allantoic fluid (P<0.05). The expression of S100G, S100A9, S100A12, ATP2B3, ATP2B4, TRPV5, TRPV6, CYP11A1, CYP2R1, CYP24, and VDR mRNAs known to be involved in calcium binding, calcium transport, and vitamin D metabolism were quantified by qPCR. Mediators of calcium and vitamin D signaling were expressed by Day 17 conceptus tissue, and endometria and placentae across gestation. Gestational day influenced the expression of S100G, S100A9, S100A12, TRPV6, VDR, and CYP24 mRNAs in endometria and placentae (P<0.05). Gestational day influenced endometrial expression of ATP2B3, and placental expression of TRPV5, ATP2B4, and CYP11A1 (P<0.05). VDR protein localized to the endoderm and trophectoderm (Day 17 conceptus) and was expressed in endometria and placentae throughout gestation. The observed spatiotemporal profile suggests a potential role of calcium and vitamin D in the establishment of pregnancy and regulation of fetal and placental growth, providing a platform for further mechanistic investigation. Summary sentence Components of vitamin D signaling, calcium transporters, and calcium-binding proteins are present at the ovine conceptus-maternal interface suggesting a potential role in mineral transport throughout gestation.
Compliance With the “Baby-Friendly Hospital Initiative for Neonatal Wards” in Russian Hospitals

Background The expansion of the Baby-Friendly Hospital Initiative to neonatal wards, known as the Neo-BFHI, provides recommendations to support breastfeeding, as outlined in the Three Guiding Principles, the expanded Ten Steps, and the International Code for Marketing of Breast-Milk Substitutes. In 2017, Russia participated in an international survey about compliance with the Neo-BFHI. Research Aim To assess breastfeeding support policies and practices in Russian neonatal wards at the country and federal district level in accordance with the Neo-BFHI recommendations. Methods This study was a prospective cross-sectional survey. We used the Neo-BFHI Self-Assessment questionnaire to collect data from neonatal wards that had all levels of care. A total of N = 60 Russian neonatal wards in hospitals that have ever been designated Baby-Friendly or planned to do so participated in the survey. Results Compliance scores at the federal district and country level ranging from 0–100 were used to summarize results. The median country overall score was 90 (IQR = 83 – 93). Respect for mothers, continuity of care, having a breastfeeding policy, and rooming-in had the highest median scores. Family-centered care, antenatal informing, skin-to-skin contact, and human milk use had the lowest median scores. Neonatal wards in the hospitals that were ever designated as Baby-Friendly had significantly higher scores than those that were never designated. Most respondents (n = 48, 80%) expressed a desire to obtain Neo-BFHI designation in their neonatal wards. Conclusion Neo-BFHI recommendations can be successfully implemented in Russian neonatal wards at hospitals designated Baby-Friendly or planning to be designated.
Adherence to antiretroviral therapy among women living with HIV/AIDS in the interior of the Brazilian state of Pará: cross-sectional study

ABSTRACT BACKGROUND: High prevalence of human immunodeficiency virus (HIV) infection and occurrence of drug-resistant strains have been recorded in northern Brazil. Abandonment of treatment and insufficient and inadequate adherence to antiretroviral therapy (ART) among people living with HIV/AIDS (PLWHA) have been recorded in the metropolitan area of Belém, the capital of the state of Pará. OBJECTIVES: To identify the sociodemographic profile and level of adherence to ART among women seen at a referral unit in the interior of Pará, northern Brazil. DESIGN AND SETTING: Cross-sectional study at a referral unit for care for PLWHA. METHODS: We included 86 women living with HIV/AIDS (WLWHA) in the Rio Caeté integrated region, northeastern Pará. Social, demographic and behavioral information, as well as the ART level, were obtained using forms that have been described in the scientific literature. Logistic regression models were used to assess associations of variables with ART. RESULTS: Most WLWHA were single (52.4%), young (47.7%) and heterosexual (97.7%), had low levels of education (63.0%), were unemployed (69.8%), had one sexual partner (75.7%), used condoms (46.7%) and were not using either licit drugs (68.7%) or illicit drugs (89.6%). Their adherence level was classified as insufficient , and only their viral load showed an association with ART. CONCLUSIONS: The participants’ low level of education and poor socioeconomic conditions may have been interfering with their adherence to ART. Such influences can be minimized through multiprofessional interventions that take the individuality of women served by the healthcare service into consideration.
Cu and Fe diffusion in rhyolitic melts during chalcocite “dissolution”: Implications for porphyry ore deposits and tektites

Abstract Copper diffusion plays an important role in natural processes, such as metal transport during the formation of magmatic-hydrothermal porphyry-type ore deposits and Cu isotope fractionation during tektite formation. Copper diffusion data in natural silicate melts, however, are limited. In this study, chalcocite (Cu2S) “dissolution” experiments were carried out using chalcocite-rhyolite diffusion “couples” to study Cu (and S) diffusion in rhyolitic melts. Instead of chalcocite dissolution as initially expected, our experiments show that Cu is transferred from the chalcocite crystal to the rhyolitic melt, and Fe is transferred from the rhyolitic melt to chalcocite, whereas the S concentration profile in the rhyolitic melt is essentially flat. From the Cu and Fe exchange profiles in the rhyolitic melts, Cu diffusivities and Fe diffusivities are obtained and reported. Copper diffusivity in rhyolitic melts containing 0.10 to 5.95 wt% H2O at temperatures of 750 to 1391 °C and pressures of 0.5 to 1.0 GPa can be described as: DCuRhy=exp⁡[−(14.75±0.35)−(0.23±0.10)w−(11647±491)−(698±117)wT], $$\begin{array}{} D_{^\text{Cu}}^{_\text{Rhy}}=\exp\Bigg[-(14.75\pm 0.35)-(0.23\pm0.10)w-\displaystyle\frac{(11647\pm491)-(698\pm117)w}{T}\Bigg], \end{array} $$ which allows the estimation of an activation energy for diffusion in dry rhyolitic melts to be 96.8 ± 4.1 kJ/mol. In the above equation, diffusivity (D) is in m2/s, T is the temperature in K, w is the H2O concentration in the rhyolitic melts in wt% and all errors reported are at 1σ level. Combining Cu diffusion data from this study and previous data in basaltic melt gives a general equation for Cu diffusivity in natural silicate melts: DCu=exp⁡[−(17.3±0.9)+(3.8±1.5)(Si+Al-H)−(4403±1094)+(9700±1921)(Si+Al-H)T], $$\begin{array}{} D_{_\text{Cu}}=\exp\Bigg[-(17.3\pm 0.9)+(3.8\pm1.5)(\text{Si}+ \text{Al-H})-\displaystyle\frac{(4403\pm1094)+(9700\pm1921) (\text{Si}+\text{Al-H})}{T}\Bigg], \end{array} $$ where Si+Al-H is the cation mole fraction of Si plus Al minus H in the silicate melt on a wet basis. Iron diffusivities obtained in this study, in anhydrous to 6 wt% H2O rhyolite, are combined with previous data to get a general equation for Fe diffusion in rhyolitic melts: DFeRhy=exp⁡[−(16.1±1.7)−(19859±2541)−(1218±135)wT]. $$\begin{array}{} D_{^\text{Fe}}^{_\text{Rhy}}=\exp\Bigg[-(16.1\pm 1.7)-\displaystyle\frac{(19859\pm2541)-(1218\pm135) w}{T}\Bigg]. \end{array} $$ Our data demonstrate that Cu diffusion is faster than H2O or Cl in rhyolitic melts containing 6 wt% water, which indicates that the scavenging and transport of Cu by a magmatic volatile phase during formation of porphyry-type ore deposits is not limited by diffusion of Cu. Based on our experimental data, Cu diffusivity is almost four orders of magnitude higher than Zn in anhydrous rhyolitic melts, which supports the explanation of more diffusive loss of Cu leading to more fractionated Cu isotopes than Zn isotopes in tektites.
Pregnancy, delivery, and neonatal outcomes among women with irritable bowel syndrome (IBS) an evaluation of over 9 million deliveries

Abstract Objective Evaluate the associations between irritable bowel syndrome (IBS) and pregnancy, delivery, and neonatal outcomes, using a population database cohort. Methods We conducted a retrospective analysis utilizing the Health Care Cost and Utilization Project-Nationwide Inpatient Sample database over 11 years from 2004 to 2014. A delivery cohort was created using ICD-9 codes. ICD-9 code 564.1 was used to extract the cases of IBS. Pregnant women with IBS (study group) were compared to pregnant women without IBS (control). A multivariate logistic regression model was used to adjust for statistically significant variables (p value <.05). Results There were a total of 9,096,788 deliveries during the study period. Of those, 8962 pregnant women were found to have IBS. The prevalence of IBS increased from 47.96 to 172.68 per 100,000 women during the study period. Compared to the control group, women with IBS were more likely to be Caucasian, older, have higher incomes and private insurance plans (p < .0001, in all cases). In addition, they were more likely to be obese, smokers, hypertensive, IVF pregnancies, have multiple gestations, thyroid disorders, chronic interstitial cystitis, fibromyalgia and have psychiatric disorders (p < .0001 in all cases). Women with IBS were more likely to experience pregnancy-induced hypertension (aOR 1.11, 95% CI 1.02–1.21), preeclampsia (aOR 1.23, 95% CI 1.09–1.38), deep venous thrombosis (aOR 2.26, 95% CI 1.12–4.57), and gestational diabetes (aOR 1.1, 95% CI 1.002–1.22) compared to the non-IBS group. Congenital anomalies were encountered in 1.7% of the IBS group compared to 0.4% in the control group (aOR 2.57, 95% CI 2.13–3.09). Conclusion When controlling for confounding effects, IBS is associated with an increased risk for preeclampsia, DVT and increased risk for congenital malformation.
Andrographis overcomes 5-fluorouracil associated chemoresistance through inhibition of DKK1 in colorectal cancer.

Colorectal cancer (CRC) ranks as the third leading cause of cancer-related deaths in the US. 5-fluorouracil (5FU)-based chemotherapeutic drug remains a mainstay of CRC treatment. Unfortunately, ~50-60% of patients eventually develop resistance to 5FU, leading to poor survival outcomes. Our previous work revealed that andrographis enhanced 5FU-induced anti-cancer activity, but the underlying mechanistic understanding largely remains unclear. In this study, we first established 5FU resistant (5FUR) CRC cells and observed that combined treatment with andrographis-5FU in 5FUR cells exhibited superior effect on cell viability, proliferation and colony formation capacity compared to individual treatments (p<0.001). To identify key genes and pathways responsible for 5FU resistance, we analyzed genome-wide transcriptomic profiling data from CRC patients who either responded or did not respond to 5FU. Among a panel of differentially expressed genes, DKK1 overexpression was a critical event for 5FU resistance. Moreover, andrographis significantly downregulated 5FU-induced DKK1 overexpression, accompanied with enhanced anti-tumor effects by abrogating downstream Akt-phosphorylation. In line with in vitro findings, andrographis enhanced 5FU-induced anti-cancer activity in mice xenografts and patient-derived tumoroids (p<0.01). In conclusion, our data provide novel evidence for andrographis-mediated reversal of 5FU resistance, highlighting its potential role as an adjunct to conventional chemotherapy in CRC.
Characterization of Nb and W Doped Titania as Catalyst Supports for Proton Exchange Membrane Fuel Cells

Niobium doped titania and tungsten doped titania prepared using a sol-gel technique were evaluated as possible catalyst support materials for proton exchange membrane fuel cells. The electrical conductivity of the doped materials prepared under different heat-treatment temperatures and partial oxygen pressures was measured. Rutile 10Nb-TiO2 was extremely conductive compared to the anatase 10Nb-TiO2. For the W doped samples the conductivity was found to be extremely low compared to the rutile 10Nb-TiO2, and W segregation was observed when the material was reduced in H2 at temperatures greater than 700dC. X-ray photoelectron spectroscopy (XPS) analysis was completed on 10Nb-TiO2 calcined at 500dC and on 10Nb-TiO2 calcined and then reduced at a range of temperatures (500dC to 900dC).
Next-generation probiotics: a promising approach towards designing personalized medicine

Abstract Second brain, forgotten organ, individual’s identity card, and host’s fingerprint are the few collective terms that are often used to describe the gut microbiome because of its variability, accountability, and its role in deciding the host’s health. Also, the understanding of this host health–gut microbiota relationship can create an opportunity to control an individual’s health by manipulating the gut microbiota composition. Several approaches like administration of probiotic, prebiotics, synbiotics, faecal microbiota transplantation have been tried to mitigate the dysbiosis originated ill effects. But the effects of these approaches are highly generic and non-specific. This creates the necessity to design personalized medicine that focuses on treatment of specific disease considering the individual specific gut microbiome. The health promoting commensals could be the new promising prophylactic and therapeutic agents for designing personalized medicine. These commensals are designated as next-generation probiotics (NGPs) and their unusual characteristics, unknown identity and special growth requirements have presented difficulties for researcher, industrial exploitation, and regulatory agencies. In this perspective, this review discusses the concept of NGPs, NGP candidates as tool for designing personalized medicine, designer probiotics as NGPs, required regulatory framework, and propose a road map to develop the NGP based product.
Association of vitamin D metabolites with cognitive function and brain atrophy in elderly individuals - the Austrian stroke prevention study

Background: Vitamin D is a well-established regulator of calcium and phosphate metabolism that has neurotrophic and neuroprotective properties. Deficiency of vitamin D has been proposed to promote cognitive dysfunction and brain atrophy. However, existing studies provide inconsistent results. Here we aimed to investigate the association between vitamin D metabolites, cognitive function and brain atrophy in a cohort of well-characterized community-dwelling elderly individuals with normal neurological status and without history of stroke and dementia. Methods: 25(OH)D3, 25(OH)D2 and 24,25(OH)2D3 were measured by liquid-chromatography tandem mass-spectrometry in serum samples from 390 community-dwelling elderly individuals. All participants underwent thorough neuropsychiatric tests capturing memory, executive function and visuopractical skills. In 139 of these individuals, MRI of the brain was performed in order to capture neurodegenerative and vascular changes. Results: Total 25(OH)D (ß=0.003, 0.037), 24,25(OH)2D3 (ß=0.0456, p=0.010) and vitamin D metabolite ratio (VMR) (ß=0.0467, p=0.012) were significantly related to memory function. Adjustment for multiple testing weakened these relationships, but trends (p≤0.10) remained. 24,25(OH)2D3 and VMR showed similar trends also for visuopractical skills and global cognitive function. No significant relationships existed between vitamin D metabolites and MRI derived indices of neurodegeneration and vascular changes. Sub-group analyses of individuals with low concentrations of 25(OH)D and 24,25(OH)2D3 showed significantly worse memory function compared to individuals with normal or high concentrations. Conclusions: Vitamin D deficient individuals appear to have a modest reduction of memory function without structural brain atrophy. Future studies should explore if vitamin D supplementation can improve cognitive function.
Comprehensive characterization of alternative splicing in renal cell carcinoma

Irregular splicing was associated with tumor formation and progression in renal cell carcinoma (RCC) and many other cancers. By using splicing data in the TCGA SpliceSeq database, RCC subtype classification was performed and splicing features and their correlations with clinical course, genetic variants, splicing factors, pathways activation and immune heterogeneity were systemically analyzed. In this research, alternative splicing was found useful for classifying RCC subtypes. Splicing inefficiency with upregulated intron retention and cassette exon was associated with advanced conditions and unfavorable overall survival of patients with RCC. Splicing characteristics like splice site strength, guanine and cytosine content and exon length may be important factors disrupting splicing balance in RCC. Other than cis-acting and trans-acting regulation, alternative splicing also differed in races and tissue types and is also affected by mutation conditions, pathway settings and the response to environmental changes. Severe irregular splicing in tumor not only indicated terrible intra-cellular homeostasis, but also changed the activity of cancer-associated pathways by different splicing effects including isoforms switching and expression regulation. Moreover, irregular splicing and splicing-associated antigens were involved in immune reprograming and formation of immunosuppressive tumor microenvironment. Overall, we have described several clinical and molecular features in RCC splicing subtypes, which may be important for patient management and targeting treatment.
Drug synergy of combinatory treatment with remdesivir and the repurposed drugs fluoxetine and itraconazole effectively impairs SARS‐CoV‐2 infection in vitro

The SARS‐COV‐2 pandemic and the global spread of coronavirus disease 2019 (COVID‐19) urgently call for efficient and safe antiviral treatment strategies. A straightforward approach to speed up drug development at lower costs is drug repurposing. Here, we investigated the therapeutic potential of targeting the interface of SARS CoV‐2 with the host via repurposing of clinically licensed drugs and evaluated their use in combinatory treatments with virus‐ and host‐directed drugs in vitro.