Miracle-dz/UniFAR-FTUs huggingface dataset:
Depletion of Adipocyte Becn1 Leads to Lipodystrophy and Metabolic Dysregulation

Becn1/Beclin-1 is a core component of the class III phosphatidylinositol 3-kinase required for autophagosome formation and vesicular trafficking. Although Becn1 has been implicated in numerous diseases such as cancer, aging, and neurodegenerative disease, the role of Becn1 in white adipose tissue and related metabolic diseases remains elusive. In this study, we show that adipocyte-specific Becn1 knockout mice develop severe lipodystrophy, leading to adipose tissue inflammation, hepatic steatosis, and insulin resistance. Ablation of Becn1 in adipocytes stimulates programmed cell death in a cell-autonomous manner, accompanied by elevated endoplasmic reticulum (ER) stress gene expression. Furthermore, we observed that Becn1 depletion sensitized mature adipocytes to ER stress, leading to accelerated cell death. Taken together, these data suggest that adipocyte Becn1 would serve as a crucial player for adipocyte survival and adipose tissue homeostasis.
Seeking or contributing? Evidence of knowledge sharing behaviours in promoting patients’ perceived value of online health communities

Health knowledge, as an important resource of online health communities (OHCs), attracts users to engage in OHCs and improve the traffics within OHCs, thereby promoting the development of OHCs. Seeking and contributing health knowledge are basic activities in OHCs and are helpful for users to solve their health‐related problems, improve their health conditions and thus influence their evaluation of OHCs (ie perceived value of OHCs). However, how do patients’ health knowledge seeking and health knowledge contributing behaviours together with other factors influence their perceived value of OHCs? We still have little knowledge.
Developmental stages in microbiota, bile acids, and clostridial species in healthy puppies

Abstract Background The fecal microbiota, fecal bile acid concentrations, and abundance of Clostridium perfringens and Clostridium difficile are altered in acute and chronic gastrointestinal disease in adult dogs. However, less is known in young puppies. Hypothesis/Objectives To determine composition of the fecal microbiota, assess development of fecal bile acid profiles, and determine the abundance of Clostridial species in puppies, young adult dogs, and adult dogs. Animals Healthy puppies from a whelping kennel (n = 53) and healthy client‐owned dogs <1 year old (n = 20) were separated into 6 age groups, then compared to client‐owned dogs over 1 year of age (n = 13). Methods Prospective observational study. Naturally voided fecal samples were analyzed by quantitative polymerase chain reaction to measure bacterial abundances. Fecal bile acids were quantified using gas chromatography‐mass spectrometry. Results Puppies up to 5 to 6 weeks of age had increased Dysbiosis Index (median [min‐max]: 5.39 [1.32‐8.6], P < .001), increased abundance of C. difficile (4.1 [0.01‐4.85] log DNA, P < .001), decreased secondary bile acid concentrations (0.61 [0.28‐5.06] μg/mg, P = .006), and decreased abundance of C. hiranonis (0.84 [0.01‐6.71], P = .005) compared to adult dogs (−4.62 [−8.36 to −0.61], 0.01 [0.01‐0.01], 4.12 [0.32‐8.94], and 6.02 [5.06‐7.00], respectively). Secondary bile acid concentration positively correlated with C. hiranonis abundance (ρ = 0.77; P < .001). Conclusions and Clinical Importance The increase in secondary bile acids and simultaneous decrease of C. difficile and C. perfringens after 5 to 6 weeks of age warrants further investigation into regulatory impacts that secondary bile acids could have on clostridial species in dogs.
Alzheimer’s diagnosis using deep learning in segmenting and classifying 3D brain MR images

Abstract Background and objectives Dementia is one of the brain diseases with serious symptoms such as memory loss, and thinking problems. According to the World Alzheimer Report 2016, in the world, there are 47 million people having dementia and it can be 131 million by 2050. There is no standard method to diagnose dementia, and consequently unable to access the treatment effectively. Hence, the computational diagnosis of the disease from brain Magnetic Resonance Image (MRI) scans plays an important role in supporting the early diagnosis. Alzheimer’s Disease (AD), a common type of Dementia, includes problems related to disorientation, mood swings, not managing self-care, and behavioral issues. In this article, we present a new computational method to diagnosis Alzheimer’s disease from 3D brain MR images. Methods An efficient approach to diagnosis Alzheimer’s disease from brain MRI scans is proposed comprising two phases: I) segmentation and II) classification, both based on deep learning. After the brain tissues are segmented by a model that combines Gaussian Mixture Model (GMM) and Convolutional Neural Network (CNN), a new model combining Extreme Gradient Boosting (XGBoost) and Support Vector Machine (SVM) is used to classify Alzheimer’s disease based on the segmented tissues. Results We present two evaluations for segmentation and classification. For comparison, the new method was evaluated using the AD-86 and AD-126 datasets leading to Dice 0.96 for segmentation in both datasets and accuracies 0.88, and 0.80 for classification, respectively. Conclusion Deep learning gives prominent results for segmentation and feature extraction in medical image processing. The combination of XGboost and SVM improves the results obtained.
A replication study of JTC bias, genetic liability for psychosis and delusional ideation

Abstract Background This study attempted to replicate whether a bias in probabilistic reasoning, or ‘jumping to conclusions’(JTC) bias is associated with being a sibling of a patient with schizophrenia spectrum disorder; and if so, whether this association is contingent on subthreshold delusional ideation. Methods Data were derived from the EUGEI project, a 25-centre, 15-country effort to study psychosis spectrum disorder. The current analyses included 1261 patients with schizophrenia spectrum disorder, 1282 siblings of patients and 1525 healthy comparison subjects, recruited in Spain (five centres), Turkey (three centres) and Serbia (one centre). The beads task was used to assess JTC bias. Lifetime experience of delusional ideation and hallucinatory experiences was assessed using the Community Assessment of Psychic Experiences. General cognitive abilities were taken into account in the analyses. Results JTC bias was positively associated not only with patient status but also with sibling status [adjusted relative risk (aRR) ratio : 4.23 CI 95% 3.46–5.17 for siblings and aRR: 5.07 CI 95% 4.13–6.23 for patients]. The association between JTC bias and sibling status was stronger in those with higher levels of delusional ideation (aRR interaction in siblings: 3.77 CI 95% 1.67–8.51, and in patients: 2.15 CI 95% 0.94–4.92). The association between JTC bias and sibling status was not stronger in those with higher levels of hallucinatory experiences. Conclusions These findings replicate earlier findings that JTC bias is associated with familial liability for psychosis and that this is contingent on the degree of delusional ideation but not hallucinations.
A new species of the genus Opisthotropis Günther, 1872 (Squamata: Natricidae) from the highlands of Kon Tum Province, Vietnam

A new species of the snake genus Opisthotropis Gunther, 1872, Opisthotropis cucae sp. nov., is described from Kon Tum Plateau in central Vietnam. It is distinguished from any other Opisthotropis species by the combination of the following characters: (1) dorsal scales entirely smooth, in 23–19–19 rows; (2) 191 ventrals; (3) 1 loreal, in contact with internasal; (4) 7 supralabials, 5 th entering orbit; (4) dorsum uniformly greyish-brown without bands or crossbars, with an irregular separation between dark dorsum and venter, greyish-yellow speckled with dark grey. An extended comparison with other species of the genus Opisthotropis species is provided together with a key to the known species of the genus. Opisthotropis cucae sp. nov. is the third new mountain stream snake described from Vietnam in the past decade. The grammatical gender of the genus Opisthotropis is discussed; this genus is feminine.
Intratumoral Injection of Clostridium novyi-NT Spores in Patients with Treatment-refractory Advanced Solid Tumors

Purpose: Intratumorally injected Clostridium novyi-NT (nontoxic; lacking the alpha toxin), an attenuated strain of C. novyi, replicates within hypoxic tumor regions resulting in tumor-confined cell lysis and inflammatory response in animals, which warrants clinical investigation. Patients and Methods: This first-in-human study (NCT01924689) enrolled patients with injectable, treatment-refractory solid tumors to receive a single intratumoral injection of C. novyi-NT across 6 dose cohorts (1 × 104 to 3 × 106 spores, 3+3 dose-escalation design) to determine dose-limiting toxicities (DLT), and the maximum tolerated dose. Results: Among 24 patients, a single intratumoral injection of C. novyi-NT led to bacterial spores germination and the resultant lysis of injected tumor masses in 10 patients (42%) across all doses. The cohort 5 dose (1 × 106 spores) was defined as the maximum tolerated dose; DLTs were grade 4 sepsis (n = 2) and grade 4 gas gangrene (n = 1), all occurring in three patients with injected tumors >8 cm. Other treatment-related grade ≥3 toxicities included pathologic fracture (n = 1), limb abscess (n = 1), soft-tissue infection (n = 1), respiratory insufficiency (n = 1), and rash (n = 1), which occurred across four patients. Of 22 evaluable patients, nine (41%) had a decrease in size of the injected tumor and 19 (86%) had stable disease as the best overall response in injected and noninjected lesions combined. C. novyi-NT injection elicited a transient systemic cytokine response and enhanced systemic tumor-specific T-cell responses. Conclusions: Single intratumoral injection of C. novyi-NT is feasible. Toxicities can be significant but manageable. Signals of antitumor activity and the host immune response support additional studies of C. novyi-NT in humans.
Five-Year Prognosis After TIA or Minor Ischemic Stroke in Asian and Non-Asian Populations

Objective To determine long-term vascular outcomes of Asian patients who experienced TIA or minor ischemic stroke and to compare the outcomes of Asian patients with those of non-Asian patients, in the context of modern guideline-based prevention strategies. Methods This is a subanalysis of the TIAregistry.org project, in which 3,847 patients (882 from Asian and 2,965 from non-Asian countries) with a recent TIA or minor ischemic stroke were assessed and treated by specialists at 42 dedicated units from 14 countries and followed for 5 years. The primary outcome was a composite of cardiovascular death, nonfatal stroke, and nonfatal acute coronary syndrome. Results No differences were observed in the 5-year risk of the primary outcome (14.0% vs 11.7%; hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.88–1.37; p = 0.41) and stroke (10.7% vs 8.5%; HR, 1.17; 95% CI, 0.90–1.51; p = 0.24) between Asian and non-Asian patients. Asian participants were at higher risk of intracranial hemorrhage (1.8% vs 0.8%; HR, 2.23; 95% CI, 1.09–4.57; p = 0.029). Multivariable analysis showed that the presence of multiple acute infarctions on initial brain imaging was an independent predictor of primary outcome and modified Rankin Scale score of >1 in both Asian (HR, 1.91; 95% CI, 1.11–3.29; p = 0.020) and non-Asian (HR, 1.39; 95% CI, 1.02–1.90; p = 0.037) patients. Conclusion The long-term risk of vascular events in Asian patients was as low as that in non-Asian patients, while Asian participants had a 2.2-fold higher intracranial hemorrhage risk. Multiple acute infarctions were independently associated with future disability in both groups. Classification of Evidence This study provides Class I evidence that among people who experienced TIA or minor stroke, Asian patients have a similar 5-year risk of cardiovascular death, stroke, and acute coronary syndrome as non-Asian patients.
The role of Topoisomerase II in replication in mammalian cells

Topoisomerase 2α (Topo2α) is an essential protein with DNA decatenating enzymatic properties, indispensable for chromosome decatenation and segregation. It is a target for a plethora of antitumour drugs and Topo2α protein levels have been associated with the success of treatment, but also drug resistance and secondary malignancies. Although unique in its ability to resolve catenated chromosomes, the role of Topo2α in other steps of DNA metabolism, such as DNA replication elongation and termination have been elusive. A thorough understanding of the role of Topo2α in the cell will not only allow for increased insight into the mechanisms it is involved in, but it will also shed light on proteins and pathways that can act as back-up in its absence, and therefore hopefully expand the basis on which to improve treatment options. Through a synthetic lethal interaction (SLI) screen with an siRNA library targeting 200 DNA repair and signalling genes, Topo2α emerged as being synthetic lethal to Werner protein (WRN), a RecQ helicase involved in maintaining genome integrity mainly in S phase, and the loss of which leads to Werner Syndrome (WS), a segmental progeroid syndrome. The screen was performed in WRN deficient cells, with the initial aim to find proteins that act to buffer against loss of viability, which is the central idea in the concept of synthetic lethality in the absence of WRN. The screen revealed an SLI between WRN and Topo2α and although we were unable to fully validate this, it spurred the question of Topo2α’s role in DNA replication. The findings in this thesis suggest that Topo2α is not required for DNA elongation and timely completion of S phase, and that simultaneous loss of the closely related isoform Topo2β does not affect replication, suggesting that these proteins do not act in parallel back-up pathways during replication. Interestingly, cells accumulate in the polyploid fraction after both depletion and inhibition of Topo2α, albeit with different kinetics. The mechanistic basis of this phenotype remains to be understood through further research, but it is highly interesting as aneuplidity and polyploidy are implicated in the initial stages of tumour development.
A study on stress response and fertility parameters in phenotypically thermotolerant and thermosensitive dairy cows during summer heat stress.

It is well documented that heat stress (HS) causes subfertility in dairy cows. However, during the last ten years we have been observing that, under high Temperature Humidity Index (THI≥75), despite the overall reduced fertility, some cows conceive at the first artificial insemination (AI). Here, we examined distinctive features of cows with conserved fertility under severe HS. From the databases of three herds, 167 lactating Holstein cows were selected; group TT cows (n=57) conceived in the previous summer (THI≥75) at the 1st AI, and group TS (n=110) failed to conceive at the same period after at least 2 consecutive AIs. The animals calved in spring, and in August, blood samples were collected during a hot day (THI≥81) for the determination of cortisol and HSP70 concentrations. In one farm, the validity of fertility data of the previous year was re-examined. In 28 cows from group TT and in 39 cows from group TS, the conception rate was examined during July and August. In 6 cows from each group (TT and TS) the estrous cycles were synchronized, ovulation was induced with GnRH (THI =80) and the concentration of the preovulatory LH surge was determined in 9 blood samples. The progesterone concentration in the ensuing cycle was determined in blood samples collected every other day. Overall, cortisol and HSP70 were significantly lower in TT group compared to TS. More (p<0.05) animals from group TT conceived at the first AI compared with those from group TS. The induced preovulatory LH surge peaked at higher level (P<0.002) in group TT than in group TS, while no difference was recorded among groups either in mean progesterone concentrations or in the duration of the ensuing estrous cycle. These results are highly suggestive that thermotolerance in some dairy cows is an inherent characteristic, warranting further genetic investigation.
Use of the ABC/2 Method to Select Patients for Thrombectomy After 6 Hours of Symptom Onset

Objective To determine whether the ABC/2 method could accurately and reliably measure infarct volume and guide thrombectomy decision in acute stroke cases presenting with late or unknown onset. Methods Four physicians who routinely use MRI for acute stroke imaging, blinded to the RAPID results, measured the diffusion-weighted imaging (DWI) infarct volume using the ABC/2 method. Measurements with ABC/2 (the index test) were compared with RAPID (the reference standard) to calculate sensitivity, specificity, and accuracy measures for various volume cutpoints. Thrombectomy decisions based on RAPID and raters' measurements using the criteria from the Diffusion-Weighted Imaging or Computerized Tomography Perfusion Assessment With Clinical Mismatch in the Triage of Wake-Up and Late-Presenting Strokes Undergoing Neurointervention With Trevo (DAWN) trial criteria were compared. Interrater and intrarater agreement was measured using kappa statistics. Results Accuracy with the ABC/2 method was greater than 80% for each rater and each volume cut point. Interrater and intrarater agreement was substantial to excellent for each volume cut point. Treatment decisions with ABC/2 volume estimations showed strong interrater and intrarater agreement, and led to similar thrombectomy decisions compared with RAPID in more than 85% of cases. Conclusion DWI infarct volume measurement using ABC/2 method shows strong accuracy and reliability and may be an acceptable alternative to RAPID software for the application of DAWN criteria for thrombectomy decision-making.
Evaluation of the Small-animal Nano Scan PET/CT System using 89Zr.

INTRODUCTION The purpose of the present work was to evaluate the imaging characteristics of 89Zr-PET in comparison with those obtained using fluorine-18 Fluorodeoxyglucose (18F-FDG) PET (a gold standard tracer in PET imaging) using a small-animal NanoScan PET/CT scanner. METHODS The system's spatial resolution, sensitivity, uniformity, and image quality were measured on a Nano Scan small-animal PET/CT scanner according to the NEMA NU4-2008 protocols. For reconstruction images, we used 2D and 3D reconstruction algorithms. The reconstruction methods included filter back projection (FBP), the ordered subsets expectation maximization (OSEM) algorithm, and the 3D Tera-Tomo algorithm, which are developed for the NanoScan small-animal PET/CT scanner. RESULTS The results obtained showed a significant difference in the spatial resolution for 89Zr as compared to 22Na and 18F when using a 2D reconstruction algorithm. Where the spatial resolution values were much enhanced by using the 3D Tera-Tomo reconstruction for each isotope, the Full width at half maximum (FWHM) values were less than 1 for all isotopes at the center of the field of view (FOV). This difference in spatial resolution is dependent on the positron range, energy and the reconstruction method. CONCLUSION The long half-life of 89Zr makes it an ideal positron emitter for performing immuno-PET, which is matched with the biological half-life of intact mAbs. 89Zr can also give several advantages over other long half-life positron emitters in relation to the overall imaging performance because of its relatively short positron range and simpler decay scheme. The values of 89Zr sensitivity that were obtained in the present study were less than those of previous studies.
Reassessing the Progress in the Production of Advanced Biofuels in the Current Competitive Environment and Beyond: What Are the Successes and Where Progress Eludes Us and Why

The concept, science, and technology of biofuels has captured the public’s imagination as well as the attention of the academic and industrial R&D communities over the last 10 years. The 2006 US DOE report has been the basis for funding three US Bioenergy Centers, and has precipitated increased research funding worldwide. Despite the large funding resources, there is little evidence to support that processes for advanced biofuels (i.e., fuel molecules more dense than ethanol) are anywhere near achieving economic feasibility. In assessing the current status of the field for biology-based processes, there has been tremendous progress in metabolic and pathway engineering and the development of synthetic-biology tools that can be applied to engineer strains. However, the economic feasibility of what is currently possible remains in doubt, especially in light of the recent low prices of oil and natural gas. Issues liming the economic feasibility are assessed and strategies to take advantage of the successful a.
Early red nucleus atrophy in relapse‐onset multiple sclerosis

No study has investigated red nucleus (RN) atrophy in multiple sclerosis (MS) despite cerebellum and its connections are elective sites of MS‐related pathology. In this study, we explore RN atrophy in early MS phases and its association with cerebellar damage (focal lesions and atrophy) and physical disability. Thirty‐seven relapse‐onset MS (RMS) patients having mean age of 35.6 ± 8.5 (18–56) years and mean disease duration of 1.1 ± 1.5 (0–5) years, and 36 age‐ and sex‐matched healthy controls (HC) were studied. Cerebellar and RN lesions and volumes were analyzed on 3 T‐MRI images. RMS did not differ from HC in cerebellar lobe volumes but significantly differed in both right (107.84 ± 13.95 mm3 vs. 99.37 ± 11.53 mm3, p = .019) and left (109.71 ± 14.94 mm3 vs. 100.47 ± 15.78 mm3, p = .020) RN volumes. Cerebellar white matter lesion volume (WMLV) inversely correlated with both right and left RN volumes (r = −.333, p = .004 and r = −.298, p = .010, respectively), while no correlation was detected between RN volumes and mean cortical thickness, cerebellar gray matter lesion volume, and supratentorial WMLV (right RN: r = −.147, p = .216; left RN: r = −.153, p = .196). Right, but not left, RN volume inversely correlated with midbrain WMLV (r = −.310, p = .008), while no correlation was observed between whole brainstem WMLV and either RN volumes (right RN: r = −.164, p = .164; left RN: r = −.64, p = .588). Finally, left RN volume correlated with vermis VIIb (r = .297, p = .011) and right interposed nucleus (r = .249, p = .034) volumes. We observed RN atrophy in early RMS, likely resulting from anterograde axonal degeneration starting in cerebellar and midbrain WML. RN atrophy seems a promising marker of neurodegeneration and/or cerebellar damage in RMS.
The DExD box ATPase DDX55 is recruited to domain IV of the 28S ribosomal RNA by its C-terminal region

ABSTRACT RNA helicases contribute to diverse aspects of RNA metabolism through their functions in re-arranging RNA structures. Identification of the remodelling targets of RNA helicases is a critical step in elucidating their cellular functions. Here, we show that, in contrast to many other ribosome biogenesis factors, the DExD box ATPase DDX55 predominantly localizes to the nucleoplasm and we identify a nuclear localization signal within the C-terminal region of the protein. DDX55 associates with pre-ribosomal subunits in human cells and is required for maturation of large subunit pre-rRNAs. Interestingly, in vitro analyses show that DDX55 selectively associates with double-stranded RNA substrates, which also stimulate its ATPase activity, and our data suggest that the C-terminal region of DDX55 contributes to this substrate specificity. The C-terminal region of DDX55 is also necessary for recruitment of the helicase to pre-ribosomes and, using in vivo crosslinking, we reveal a binding site for DDX55 in helix H62 of the 28S ribosomal RNA. Taken together, these data highlight the importance of the C-terminal region of DDX55 in substrate specificity and recruitment, and identify domain IV as a potential remodelling target of DDX55 during LSU biogenesis.