Miracle-dz/UniFAR-FTUs huggingface dataset:
Chikungunya virus populations experience diversity- dependent attenuation and purifying intra-vector selection in Californian Aedes aegypti mosquitoes

Chikungunya virus (Togaviridae, Alphavirus; CHIKV) is a mosquito-borne global health threat that has been transmitted transiently in the southeastern United States. A primary CHIKV mosquito vector, Aedes aegypti, was recently established in the populous state of California, but the vector competence of Californian mosquitoes is unknown. Explosive CHIKV epidemics since 2004 have been associated with the acquisition of mosquito-adaptive mutations that enhance transmission by Ae. aegypti or Ae. albopictus. As a highly mutable RNA virus, CHIKV has the potential for extensive and rapid genetic diversification in vertebrate hosts and mosquito vectors. We previously demonstrated that expansion of CHIKV diversity in cell culture allows for greater adaptability to novel selection pressures, and that CHIKV fidelity variants are able to diversify more than wildtype (WT) CHIKV in mice. The evolution of intra-vector CHIKV populations and the correlation between CHIKV population diversity and infectivity and transmissibility in mosquitoes has not yet been studied. Here, we address these gaps in knowledge via experimental infection of Ae. aegypti from California with WT and fidelity variant CHIKV. We show that Ae. aegypti from California are highly competent vectors for CHIKV. We also report that CHIKV fidelity variants diversify more than WT in mosquitoes and exhibit attenuated infectivity at the level of the midgut. Furthermore, we demonstrate that intra-vector populations of CHIKV are subjected to purifying selection in mosquito bodies, and sequences of non-coding CHIKV regions are highly conserved. These findings will inform public health risk assessment for CHIKV in California and improve our understanding of constraints to CHIKV evolution in mosquitoes.
Die unklare Leberraumforderung

Abstract Unknown liver lesions represent a common clinical challenge, for example in the context of routine ultrasound examinations of primary care physicians. There are different data on the prevalence of primary liver lesions in the literature. As such, a forensic autopsy series described focal liver lesions in about 50 % of all examined men between 35 and 69 years of age with an increasing incidence for older people. In the diagnostic work-up of unclear liver lesions, a careful distinction between lesions that occur in asymptomatic and healthy individuals and are benign in over 95 % of cases, and lesion found in patients with pre-existing malignant, inflammatory or cirrhotic disease must be made. The main goal in the diagnosis of unclear liver lesions is to prove the benignity of the lesion and to exclude a malignant cause as reliably as possible. In case of benign lesions, an attempt should be made to achieve an exact classification. The most common benign focal liver lesions include liver cysts, focal fatty liver deposition or sparing, haemangiomas, focal calcifications, focal nodular hyperplasia (FNH), nodular regenerative hyperplasia, biliary hamartomas (von-Meyenburg complexes) and hepatocellular adenomas. Abscesses, inflammatory infiltrations or pseudotumors as well as sites of extramedullary haematopoiesis are observed much less frequently. Among the most frequent malignant focal liver lesions are metastases of other tumor entities such as colorectal cancer or pancreatic adenocarcinoma as well as hepatocellular carcinoma (HCC) and cholangiocellular carcinoma (CCA). Other entities such as hepatic lymphomas or mesenchymal malignant neoplasia are extremely rare.
In Vitro Effects of Vaspin on Porcine Granulosa Cell Proliferation, Cell Cycle Progression, and Apoptosis by Activation of GRP78 Receptor and Several Kinase Signaling Pathways Including MAP3/1, AKT, and STAT3

Vaspin, a visceral adipose tissue-derived serine protease inhibitor, is expressed in the porcine ovary; it induces the activation of various kinases and steroidogenesis. The aim of this study was to examine the effect of vaspin on granulosa (Gc) proliferation, cell cycle regulation, and apoptosis. Porcine Gc was incubated with vaspin (0.01–10 ng/mL) for 24 to 72 h, proliferation was measured using alamarBlue assay, cell cycle progression was assessed using flow cytometry, and cyclin (D, E, and A) protein expression was measured using immunoblotting. Apoptosis was assessed by measuring caspase activity using Caspase-glo 3/7 assay. Furthermore, histone-associated DNA fragments levels were measured using a cell-death detection ELISA; BAX (bcl-2-like protein 4), BCL2 (B-cell lymphoma 2), caspases (-3, -8, and -9), p53 mRNA, and protein expression were assessed using real time PCR and immunoblotting. We found that vaspin significantly enhanced Gc proliferation and cell cycle progression into the S and G2/M phases and decreased apoptosis. We observed that siRNA silencing of the glucose-regulated protein (GRP78) receptor and pharmacological inhibitors of mitogen-activated kinase (MAP3/1/ERK1/2), Janus kinase (STAT3) and protein kinase B (AKT) blocked the ability of vaspin cell proliferation and enhanced caspase-3/7 activities. These results suggest that vaspin via mitogenic effect on porcine Gc acts as a new regulator of ovarian growth, development, or folliculogenesis.
One-to-Many Single Entity Electrochemistry Biosensing for Ultrasensitive Detection of microRNA.

Single-entity electrochemistry (SEEC), a promising method for biosensing, has an intrinsic limitation on sensitivity since at most one colliding entity can be successfully triggered by one target. Here, we take advantage of one-to-many (1:n) signal amplification to develop a new single-entity electrochemistry biosensing (SEECBS), integrating satellite magnetic nanoparticle (MN)-DNA-Pt nanoparticle (NP) conjugates, duplex-specific nuclease (DSN) assisted Pt NPs releasing with stabilization and effective collision of small sized and nearly naked Pt NPs. Compared with conventional SEECBS, the 1:n SEECBS can successfully enrich ∼2 nM Pt NPs by adding 50 aM microRNA (miRNA), in other words, ∼4×107 Pt NPs can be triggered by one target. The proposed SEECBS allows the detection of 47 aM miRNA-21, nearly 6 orders of magnitude lower than the previous work, and discrimination of non-target miRNAs containing even single-nucleotide mismatch. Besides, this method has also been successfully demonstrated for quantification of miRNA in different cell lines. Therefore, the proposed method holds great potential for the application of SEECBS in early diagnosis and prognosis monitoring of cancer.
Investigational drugs in development for hypertriglyceridemia: a coming-of-age story

ABSTRACT Introduction: Elevated triglyceride (TG) level is a prevalent condition in the general population and in patients with cardiovascular (CV) risk even under statin therapy. Severe hypertriglyceridemia (HTG) puts patients at risk for acute pancreatitis. Several TG-lowering drugs failed in clinical trials, but subgroup analyses suggest that high-risk patients, such as those with atherogenic dyslipidemia or diabetes, benefit from TG lowering. Areas covered: We review advances for TG-lowering drugs in clinical development. These include selective PPARα modulators, omega-3 fatty acid formulations that have been approved for severe HTG, and inhibitors of apolipoprotein C-III, angiopoietin-like-3 or microsomal transfer protein. Lessons learned from the success of the phase 3 trial REDUCE-IT with high-dose icosapent ethyl are also reviewed. Expert opinion: We believe that TG-lowering therapies are coming of age as they will allow to treat patients with high CV risk and moderate HTG, including T2D subjects, as well as patients with severe HTG or even homozygous familial hypercholesterolemia, all of which being ‘optimally’ treated with a statin. More studies on the impact of therapy on quality of life in patients with severe HTG should be conducted with the help of patient registries.
The proteasome regulator PI31 is required for protein homeostasis, synapse maintenance, and neuronal survival in mice

Significance The conserved proteasome-binding protein PI31 serves as an adapter to couple proteasomes with cellular motors to mediate their transport to distal tips of neurons where protein breakdown occurs. We generated global and conditional PI31 knockout mouse strains and show that this protein is required for protein homeostasis, and that its conditional inactivation in neurons disrupts synaptic structures and long-term survival. This work establishes a critical role for PI31 and local protein degradation in the maintenance of neuronal architecture, circuitry, and function. Because mutations in the PI31 pathway cause neurodegenerative diseases in humans, reduced PI31 activity may contribute to the etiology of these diseases. Proteasome-mediated degradation of intracellular proteins is essential for cell function and survival. The proteasome-binding protein PI31 (Proteasomal Inhibitor of 31kD) promotes 26S assembly and functions as an adapter for proteasome transport in axons. As localized protein synthesis and degradation is especially critical in neurons, we generated a conditional loss of PI31 in spinal motor neurons (MNs) and cerebellar Purkinje cells (PCs). A cKO of PI31 in these neurons caused axon degeneration, neuronal loss, and progressive spinal and cerebellar neurological dysfunction. For both MNs and PCs, markers of proteotoxic stress preceded axonal degeneration and motor dysfunction, indicating a critical role for PI31 in neuronal homeostasis. The time course of the loss of MN and PC function in developing mouse central nervous system suggests a key role for PI31 in human neurodegenerative diseases.
Default mode network anatomy and function is linked to pediatric concussion recovery

Objective To determine whether anatomical and functional brain features relate to key persistent post-concussion symptoms (PPCS) in children recovering from mild traumatic brain injuries (mTBI), and whether such brain indices can predict individual recovery from PPCS. Methods 110 children with mixed recovery following mTBI were seen at the concussion clinic at Neurology department Alberta Children’s Hospital. The primary outcome was the Post-Concussion Symptom Inventory (PCSI, parent proxy). Sleep disturbance scores (PCSI sub-domain) and the Neurocognition Index (CNS Vital Signs) were also measured longitudinally. PPCS was assessed at 4 weeks post-injury and 8-10 weeks post-injury. Grey matter volumes were assessed using magnetic resonance imaging (MRI) and voxel-based morphometry. Functional connectivity was estimated using resting-state MRI. Two complementary machine learning methods were used to assess if the combination of grey matter and functional connectivity indices carried meaningful prognostic information. Results Higher scores on a composite index of sleep disturbance, including fatigue, were associated with converging decreases in grey matter volume and local functional connectivity in two key nodes of the default mode network: the posterior cingulate cortex and the medial prefrontal cortex. Sleep-related disturbances also significantly correlated with reductions in functional connectivity between these brain regions. The combination of structural and functional brain indices associated to individual variations in the default mode network accurately predicted clinical outcomes at follow-up (area under the curve = 0.86). Interpretation These results highlight that the function-structure profile of core default mode regions underpins sleep-related problems following mTBI and carries meaningful prognostic information for pediatric concussion recovery.
Habitual Nut Exposure, Assessed by Dietary and Multiple Urinary Metabolomic Markers, and Cognitive Decline in Older Adults: The InCHIANTI Study.

SCOPE We prospectively evaluated the association between self-reported dietary intake and urinary metabolomic markers of habitual nut exposure with cognitive decline over a 3-year follow-up in an older Italian population. METHODS AND RESULTS We selected 119 older participants, from the InCHIANTI cohort based on self referred nut intake: the non-nut consumer (n = 72) and the regular nut consumer (≥2.9 g/d, n = 47) groups. Nut exposure was measured at baseline either with the use of a validated food frequency questionnaire or with an HPLC-Q-ToF-MS metabolomic approach. Three years after, 28 from non-consumers group and 10 from consumers group experienced cognitive decline. Dietary nut exposure was characterized by urinary metabolites of polyphenols and fatty acids pathways. Nut consumption estimated either by the dietary marker or by the urinary marker model was in both cases associated with less cognitive decline (OR: 0.78, 95% CI: 0.61,0.99; P = 0.043 and OR: 0.995, 95% CI: 0.991,0.999; P = 0.016, respectively) with AUCs 73.2 (95% CI: 62.9,83.6) and 73.1 (62.5,83.7), respectively. CONCLUSIONS A high intake of nuts may protect older adults from cognitive decline. The use of a panel of metabolites provides accurate and complementary information of the nut exposure and reinforces the results obtained using dietary information. This article is protected by copyright. All rights reserved.
Tensor Low-Rank Representation for Data Recovery and Clustering

Multi-way or tensor data analysis has attracted increasing attention recently, with many important applications in practice. This article develops a tensor low-rank representation (TLRR) method, which is the first approach that can exactly recover the clean data of intrinsic low-rank structure and accurately cluster them as well, with provable performance guarantees. In particular, for tensor data with arbitrary sparse corruptions, TLRR can exactly recover the clean data under mild conditions; meanwhile TLRR can exactly verify their true origin tensor subspaces and hence cluster them accurately. TLRR objective function can be optimized via efficient convex programing with convergence guarantees. Besides, we provide two simple yet effective dictionary construction methods, the simple TLRR (S-TLRR) and robust TLRR (R-TLRR), to handle slightly and severely corrupted data respectively. Experimental results on two computer vision data analysis tasks, image/video recovery and face clustering, clearly demonstrate the superior performance, efficiency and robustness of our developed method over state-of-the-arts including the popular LRR and SSC methods.
Non-pharmacological Approach in the Management of Functional Dyspepsia

Functional dyspepsia (FD) is a common functional gastrointestinal disease which bears a significant burden on society and individuals. Despite the high prevalence of FD, its pathophysiology remains poorly understood and the treatment options are limited and unsatisfactory. In the absence of effective pharmacological treatments for FD, non-pharmacological approaches, including: reassurance, lifestyle modification, psychotherapy, dietary interventions, medical food, acupuncture, and electrical stimulation and modulation are sought after by many physicians and FD patients. In this article, we review clinical studies which investigate non-pharmacological therapies for FD. We will also discuss potential mechanisms involved in the therapeutic effects of these non-pharmacological approaches. Though the evidences to support the routine use of the non-pharmacological management is still lacking, the non-invasive nature and potentially minimal side-effects of these therapies may be attractive in the FD management. In order to confirm the clinical effectiveness of these non-pharmacological approaches, more well-conducted, methodologically rigorous, and large-scaled clinical trials are required.
The Potential Selective Cytotoxicity of Poly (L- Lactic Acid)-Based Scaffolds Functionalized with Nanohydroxyapatite and Europium (III) Ions toward Osteosarcoma Cells

Osteosarcoma (OSA) is malignant bone tumor, occurring in children and adults, characterized by poor prognosis. Despite advances in chemotherapy and surgical techniques, the survival of osteosarcoma patients is not improving significantly. Currently, great efforts are taken to identify novel selective strategies, distinguishing between cancer and normal cells. This includes development of biomimetic scaffolds with anticancer properties that can simultaneously support and modulate proper regeneration of bone tissue. In this study cytotoxicity of scaffolds composed from poly (L-lactic acid) functionalized with nanohydroxyapatite (nHAp) and doped with europium (III) ions—10 wt % 3 mol % Eu3+: nHAp@PLLA was tested using human osteosarcoma cells: U-2 OS, Saos-2 and MG-63. Human adipose tissue-derived stromal cells (HuASCs) were used as non-transformed cells to determine the selective cytotoxicity of the carrier. Analysis included evaluation of cells morphology (confocal/scanning electron microscopy (SEM)), metabolic activity and apoptosis profile in cultures on the scaffolds. Results obtained indicated on high cytotoxicity of scaffolds toward all OSA cell lines, associated with a decrease of cells’ viability, deterioration of metabolic activity and activation of apoptotic factors determined at mRNA and miRNA levels. Simultaneously, the biomaterials did not affect HuASCs’ viability and proliferation rate. Obtained scaffolds showed a bioimaging function, due to functionalization with luminescent europium ions, and thus may find application in theranostics treatment of OSA.
ARMS-PCR VERSUS AS-PCR TO EVALUATE JAK2V617F MUTATION IN PATIENTS WITH NON-CML MYELOPROLIFERATIVE NEOPLASMS

فده و هنيمز : JAK2 ا يروتپسر ريغ زانيك نيزوريت كي وليم تلالاتخا رد يمهم شقن هك تس ئ يم افيا يدي دنك . خا ـ ي ار شهج باستكا ي JAK2 V617F رد دادعت ز ي دا ي زا ب ي نارام مسلاپوئن هب لاتبم ياه ويتارفيلورپوليم (MPNs) يياـسانش هدـش تسا . ا ي ن يشان شهج زا غت يي ر G هب T رد توئلكون ـ ي د 1849 رد نوزـگا 12 زا نژ JAK2 عـقاو رـب ور ي موزوـمورك 9 تسا هك رجنم هب اج ي زگ ي ن ي سا ي مآد ي هن نف ي ل نلاآ ي ن هب اـج ي ـ لاو ي ن رد عقوم ـ ي ت 617 زا ـ پ تور ي ي ن JAK2 ـم ي ددرـگ . رد شهج لزلزتم ريثكت متسيس شور ود رضاح هعلاطم اه ) ARMS-PCR ( يور رـب DNA يصاصـتخا لـلآ و ) AS-PCR ( رـب يور RNA هدش هسياقم شهج نيا يبايزرا رد دنا . يسررب شور : هعلاطم دوب يبرجت عون زا هدش ماجنا . هـعلاطم نيا رد شهج JAK2 V617F هنومن شور اب اصت يريگ رد ،هداس يفد 58 هـب لاتـبم ناـمرد لاـح رد اـي ديدج صيخشت اب راميب يميخدب شور اب ويتارفيلورپوليم ياه ARMS-PCR و AS-PCR دنتفرگ رارق يبايزرا دروم . زا هنومن هس ،جياتن دييات يارب دروم ناراميب Sequencing تـفرگ رارق . هتفاي اه : شور ود رـه اـب ARMS-PCR و AS-PCR هباشـم جياـتن ناراـميب رد ي لپ ي س ي مت ي ارو ) 6 / 86 (% ناراميب و م ي فول ي زورب هيلوا ) 5 / 61 % ( دمآ تسد هب . ناراميب رد اما سوبمورت ي مت ي شور اـب هـيلوا
Biogenesis of Developmental Master Regulatory 27nt-RNAs in Stylonychia—Can Coding RNA Turn into Non-Coding?

In the ciliate Stylonychia, somatic macronuclei differentiate from germline micronuclei during sexual reproduction, accompanied by developmental sequence reduction. Concomitantly, over 95% of micronuclear sequences adopt a heterochromatin structure characterized by the histone variant H3.4 and H3K27me3. RNAi-related genes and histone variants dominate the list of developmentally expressed genes. Simultaneously, 27nt-ncRNAs that match sequences retained in new macronuclei are synthesized and bound by PIWI1. Recently, we proposed a mechanistic model for ‘RNA-induced DNA replication interference’ (RIRI): during polytene chromosome formation PIWI1/27nt-RNA-complexes target macronucleus-destined sequences (MDS) by base-pairing and temporarily cause locally stalled replication. At polytene chromosomal segments with ongoing replication, H3.4K27me3-nucleosomes become selectively deposited, thus dictating the prospective heterochromatin structure of these areas. Consequently, these micronucleus-specific sequences become degraded, whereas 27nt-RNA-covered sites remain protected. However, the biogenesis of the 27nt-RNAs remains unclear. It was proposed earlier that in stichotrichous ciliates 27nt-RNA precursors could derive from telomere-primed bidirectional transcription of nanochromosomes and subsequent Dicer-like (DCL) activity. As a minimalistic explanation, we propose here that the 27nt-RNA precursor could rather be mRNA or pre-mRNA and that the transition of coding RNA from parental macronuclei to non-coding RNAs, which act in premature developing macronuclei, could involve RNA-dependent RNA polymerase (RDRP) activity creating dsRNA intermediates prior to a DCL-dependent pathway. Interestingly, by such mechanism the partition of a parental somatic genome and possibly also the specific nanochromosome copy numbers could be vertically transmitted to the differentiating nuclei of the offspring.
Relationship between Helicobacter pylori infection and serum pepsinogen levels in patients with chronic gastritic diseases or gastric cancer

Objective To investigate the impact of Helicobacter pylori (H. pylori) on the level of serum pepsinogen (PG) subgroup (PG Ⅰ and PG Ⅱ) in patients with chronic gastric diseases and gastric cancer. Methods A total of 263 patients with symptoms of digestive tract diseases treated in the gastroenterology department of the Affiliated Hospital of Ningxia Medical University from October 2010 to April 2011 (67 cases of gastric cancer, 104 cases of atrophic gastritis, and 92 cases of peptic ulcer) were enrolled for the study. Eighty-eight healthy people were entered as normal control. The H. pylori status was determined by rapid urease test, and the level of serum pepsinogen (PG Ⅰ and PG Ⅱ) was measured by enzyme-linked immunosorbent assay (ELISA). Results The positive rate of HP infection for peptic ulcer was the highest (71.7%), whereas that of atrophic gastritis, gastric cancer and normal control was 63.5%, 56.7% and 55.6%, respectively, there was no significant difference between groups (P > 0.05). Compared with the normal control, serum PG Ⅰ level and PG Ⅰ/PG Ⅱ ratio were lower in atrophic gastritis patients, whereas that of PG Ⅱ elevated; PG Ⅰ/PG Ⅱ ratio of peptic ulcer patients was lowered, whereas their PGⅠ and PG Ⅱ elevated (P 0.05). Serum PG Ⅰ, PG Ⅱ and PG Ⅰ/PG Ⅱ ratio in patients with atrophic gastritis plus intestinal metaplasia, and those plus dysplasia were not significant different from those in patients with atrophic gastritis alone (P > 0.05), while the PG Ⅰ/PG Ⅱ ratio was higher when compared with that in patients with gastric cancer (PP 0.05). Conclusion H. pylori infection has little relation with changes in serum pepsinogen level in patients with chronic gastric diseases or gastric cancer.