Miracle-dz/UniFAR-FTUs huggingface dataset:
E1B-55K mediated regulation of RNF4 STUbL promotes HAdV gene expression 1

25 HAdV E1B-55K is a multifunctional regulator of productive viral replication and 26 oncogenic transformation in non-permissive mammalian cells. These functions 27 depend on E1B-55K’s posttranslational modification with the SUMO protein and its 28 binding to HAdV E4orf6. Both early viral proteins recruit specific host factors to 29 form an E3 Ubiquitin ligase complex that targets antiviral host substrates for 30 proteasomal degradation. Recently, we reported that the PML-NB-associated factor 31 Daxx represses efficient HAdV productive infection and is proteasomally degraded 32 via a SUMO-E1B-55K-dependent, E4orf6-independent pathway, the details of which 33 remained to be established. 34 RNF4, a cellular SUMO-targeted Ubiquitin ligase (STUbL), induces ubiquitinylation 35 of specific SUMOylated proteins and plays an essential role during DNA repair. 36 Here, we show that E1B-55K recruits RNF4 to the insoluble nuclear matrix fraction 37 of the infected cell to support RNF4/Daxx association, promoting Daxx PTM, and 38 thus inhibiting this antiviral factor. Removing RNF4 from infected cells using RNAi 39 resulted in blocking the proper establishment of viral replication centers and 40 significantly diminished viral gene expression. These results provide a model for 41 how HAdV antagonize the antiviral host responses by exploiting the functional 42 capacity of cellular STUbLs. Thus, RNF4 and its STUbL function represent a positive 43 factor during lytic infection and a novel candidate for future therapeutic antiviral 44 intervention strategies. 45 factor Daxx modulate Daxx PTM. antiviral gene expression in RNF4 cells. our data E1B-55K Daxx PTM
Pharmacokinetics of Sustained-release and Extended‑release Buprenorphine in Mice after Surgical Catheterization.

The Guide for the Care and Use of Laboratory Animals strongly encourages the use of pharmaceutical-grade chemicals and analgesics. Sustained-release buprenorphine (SRB) is administered extralabel to rodents to mitigate moderate to severe pain. An FDA indexed buprenorphine formulation-extended-release buprenorphine (XRB)-has recently become available and is currently the only pharmaceutical-grade slow-release buprenorphine formulation approved for use in mice and rats. However, no studies have directly compared the pharmacokinetic parameters of SRB and XRB in surgically catheterized mice. To this end, we compared the plasma buprenorphine concentrations and pharmacokinetic parameters of SRB and XRB in mice after surgical catheterization. We hypothesized that mice treated before surgery with SRB or XRB would have circulating buprenorphine concentrations that exceeded the therapeutic threshold for as long as 72 h after surgery. Male and female C57Bl/6J mice were anesthetized, treated with a single dose of either SRB (1 mg/kg SC) or XRB (3.25 mg/kg SC), and underwent surgical catheterization. Arterial blood samples were collected at 6, 24, 48, and 72 h after administration. Weight loss after surgery (mean ± SEM) was similar between groups (SRB: males, 12% ± 2%; females, 8% ± 2%; XRB: males, 12% ± 1%; females, 8% ± 1%). Both SRB and XRB maintained circulating buprenorphine concentrations above the therapeutic level of 1.0 ng/mL for 72 h after administration. Plasma buprenorphine concentrations at 6, 24, and 48 h were significantly greater (3- to 4-fold) with XRB than SRB, commensurate with XRB's higher dose. These results support the use of either SRB or XRB for the alleviation of postoperative pain in mice. The availability of FDA-indexed XRB increases options for safe and effective pharmaceutical-grade analgesia in rodents.
Multimodality Imaging in Primary Progressive Aphasia

SUMMARY: Primary progressive aphasia is a clinically and neuropathologically heterogeneous group of progressive neurodegenerative disorders, characterized by language-predominant impairment and commonly associated with atrophy of the dominant language hemisphere. While this clinical entity has been recognized dating back to the 19th century, important advances have been made in defining our current understanding of primary progressive aphasia, with 3 recognized subtypes to date: logopenic variant, semantic variant, and nonfluent/agrammatic variant. Given the ongoing progress in our understanding of the neurobiology and genomics of these rare neurodegenerative conditions, accurate imaging diagnoses are of the utmost importance and carry implications for future therapeutic triaging. This review covers the diverse spectrum of primary progressive aphasia and its multimodal imaging features, including structural, functional, and molecular neuroimaging findings; it also highlights currently recognized diagnostic criteria, clinical presentations, histopathologic biomarkers, and treatment options of these 3 primary progressive aphasia subtypes.
Association of amygdala size with stress perception: Findings of a transversal study across the lifespan

Daily routines are getting increasingly stressful. Interestingly, associations between stress perception and amygdala volume, a brain region implicated in emotional behaviour, have been observed in both younger and older adults. Life stress, on the other hand, has become pervasive and is no longer restricted to a specific age group or life stage. As a result, it is vital to consider stress as a continuum across the lifespan. In this study, we investigated the relationship between perceived stress and amygdala size in 272 healthy participants with a broad age range. Participants were submitted to a structural magnetic resonance imaging (MRI) to extract amygdala volume, and the Perceived Stress Scale (PSS) scores were used as the independent variable in volumetric regressions. We found that perceived stress is positively associated with the right amygdala volume throughout life.
Evaluation of Compensation Strategies for Gait Impairment in Patients With Parkinson Disease

Background and Objectives Compensation strategies are essential in Parkinson disease (PD) gait rehabilitation. However, besides external cueing, these strategies have rarely been investigated systematically. We aimed to perform the following: (1) establish the patients' perspective on the efficacy and usability of 5 different compensation strategies; (2) quantify the efficacy of these strategies on spatiotemporal gait parameters; and (3) explore associations between the effects of specific strategies and patient characteristics. Methods We recruited persons with PD and self-reported disabling gait impairments for this laboratory-based, within-subject study. Clinimetrics included the following: questionnaires (New Freezing of Gait Questionnaire, Vividness of Movement Imagery Questionnaire, Goldsmiths Musical Sophistication Index), cognitive assessments (Attentional Network Test and Montreal Cognitive Assessment [MoCA], Brixton), and physical examinations (Movement Disorders Society Unified Parkinson's Disease Rating Scale [MDS-UPDRS III], Mini-Balance Evaluation Systems Test, tandem gait, and rapid turns test). Gait assessment consisted of six 3-minute trials of continuous walking around a 6-m walkway. Trials comprised the following: (1) baseline gait; (2) external cueing; (3) internal cueing; (4) action observation; (5) motor imagery; and (6) adopting a new walking pattern. Spatiotemporal gait parameters were acquired using 3-dimensional motion capture analysis. Strategy efficacy was determined by the change in gait variability compared with baseline gait. Associated patient characteristics were explored using regression analyses. Results A total of 101 participants (50 men; median [range] age: 66 [47–91] years) were included. The effects of the different strategies varied greatly among participants. While participants with higher baseline variability showed larger improvements using compensation strategies, participants without freezing of gait, with lower MDS-UPDRS III scores, higher balance capacity, and better performance in orienting attention also showed greater improvements in gait variability. Higher MoCA scores were associated with greater efficacy of external cueing. Discussion Our findings support the use of compensation strategies in gait rehabilitation for PD but highlight the importance of a personalized approach. Even patients with high gait variability are able to improve through the application of compensation strategies, but certain levels of cognitive and functional reserve seem necessary to optimally benefit from them.
Topological solutions in dual formulation of Yang-Mills theories

We review briefly the emerging picture of the confinement-deconfinement phase transition as transition from four-dimensional to three-dimensional non-perturbative physics. In particular we consider the so called magnetic component of the Yang-Mills plasma. We comment on the recent lattice observation that the thermal monopoles in SU(2) gauge theories appear to possess both magnetic and electric color fields. We attempt to fit the observation into the general scheme of Yang-Mills defects developed earlier within the Sakai-Sugimoto model. The geometric features of the defects in the Yang-Mills vacuum reflect the topology of extra dimensions in this model. We favor the classification which assumes that the color magnetic and electric of the monopoles are not parallel to each other. The prediction can be checked on the lattice.
Abnormal cerebral microvascular perfusion and reactivity in female offspring of reduced uterine perfusion pressure (RUPP) mice model

Children born from women with preeclampsia have alterations in cerebral neurovascular development and a high risk for developing cognitive alterations. Because cerebral blood vessels are critical components in cerebrovascular development, we evaluated the brain microvascular perfusion and microvascular reactivity (exposed to external stimuli of warm and cold) in pups born to preeclampsia-like syndrome based on the reduction of uterine perfusion (RUPP). Also, we evaluate the angiogenic proteomic profile in those brains. Pregnant mice showed a reduction in uterine flow after RUPP surgery (−40 to 50%) associated with unfavorable perinatal results compared to sham mice. Furthermore, offspring of the RUPP mice exhibited reduced brain microvascular perfusion at postnatal day 5 (P5) compared with offspring from sham mice. This reduction was preferentially observed in females. Also, brain microvascular reactivity to external stimuli (warm and cold) was reduced in pups of RUPP mice. Furthermore, a differential expression of the angiogenic profile associated with inflammation, extrinsic apoptotic, cancer, and cellular senescence processes as the primary signaling impaired process was found in the brains of RUPP-offspring. Then, offspring (P5) from preeclampsia-like syndrome exhibit impaired brain perfusion and microvascular reactivity, particularly in female mice, associated with differential expression of angiogenic proteins in the brain tissue.
Behavioural and Electrophysiological Evaluation of Loudness Growth in Clinically Normal Hearing Tinnitus Patients with and without Hyperacusis

Introduction: The common mechanism of tinnitus, hyperacusis, and loudness perception is hypothesized to be related to central gain. Although central gain increases with attempts to compensate hearing loss, reduced input can also be observed in those with clinically normal hearing. This study aimed to evaluate the loudness growth function of tinnitus patients with and without hyperacusis using behavioural and electrophysiological methods. Methods: The study consists of three groups with a total of 60 clinically normal hearing subjects, including the control group (10 men and 10 women; mean age 39.8, SD 11.8 years), tinnitus group (10 men and 10 women; mean age 40.9, SD 12.2 years), and hyperacusis group (also have tinnitus) (7 men and 13 women; mean age 38.7, SD 14.6 years). Loudness discomfort levels (LDLs), categorical loudness scaling (CLS), and cortical auditory evoked potentials were used for the evaluation of loudness growth. N1-P2 component amplitudes and latencies were measured. Results: LDL results of 500, 1,000, 2,000, 4,000, and 8,000 Hz showed a significant difference between the hyperacusis group and the other two groups (p < 0.001). In the loudness scale test performed with 500 Hz and 2,000 Hz narrow-band noise (NBN) stimulus, a significant difference was observed between the hyperacusis group and the other two groups in the “medium,” “loud,” and “very loud” categories (p < 0.001). In the cortical examination performed with 500 Hz and 2,000 Hz NBN stimulus at 40, 60, and 80 dB nHL intensities, no significant difference was observed between the groups in the N1, P2 latency, and N1-P2 peak-to-peak amplitude. Conclusion: Although the hyperacusis group is significantly different between groups in behavioural tests, the same cannot be said for electrophysiological tests. In our attempt to differentiate tinnitus and hyperacusis with electrophysiological tests over the loudness growth function, N1 and P2 responses were not seen as suitable methods. However, it appears to be beneficial to use CLS in addition to LDLs in behavioural tests.
Outcomes in Patients with Poor-Risk Cytogenetics with or without TP53 Mutations Treated with Venetoclax and Azacitidine

Abstract Purpose: To evaluate efficacy and safety of venetoclax + azacitidine in treatment-naïve patients with acute myeloid leukemia harboring poor-risk cytogenetics and TP53mut or TP53wt. Patients and Methods: We analyzed data from a phase III study (NCT02993523) comparing venetoclax (400 mg orally days 1–28) + azacitidine (75 mg/m2 days 1–7) or placebo + azacitidine, and from a phase Ib study (NCT02203773) of venetoclax + azacitidine. Patients were ineligible for intensive therapy. TP53 status was analyzed centrally; cytogenetic studies were performed locally. Results: Patients (n = 127) with poor-risk cytogenetics receiving venetoclax + azacitidine (TP53wt = 50; TP53mut = 54) were compared with patients with poor-risk cytogenetics (n = 56) receiving azacitidine alone (TP53wt = 22; TP53mut = 18). For poor-risk cytogenetics + TP53wt patients, venetoclax + azacitidine versus azacitidine alone resulted in composite remission rates (CRc) of 70% versus 23%, median duration of remission (DoR) of 18.4 versus 8.5 months, and median overall survival (OS) of 23.4 versus 11.3 months, respectively. Outcomes with venetoclax + azacitidine were comparable with similarly treated patients with intermediate-risk cytogenetics and TP53wt. For poor-risk cytogenetics + TP53mut patients, venetoclax + azacitidine versus azacitidine alone resulted in CRc of 41% versus 17%, median DoR of 6.5 versus 6.7 months, and median OS of 5.2 versus 4.9 months, respectively. For poor-risk cytogenetics + TP53mut patients, predominant grade ≥3 adverse events (AE) for venetoclax + azacitidine versus azacitidine were febrile neutropenia (55%/39%), thrombocytopenia (28%/28%), neutropenia (26%/17%), anemia (13%/6%), and pneumonia (28%/33%). AEs were comparable between TP53mut and TP53wt patients. Conclusions: In poor-risk cytogenetics + TP53mut patients, venetoclax + azacitidine improved remission rates but not DoR or OS compared with azacitidine alone. However, in poor-risk cytogenetics + TP53wt patients, venetoclax + azacitidine resulted in higher remission rates and longer DoR and OS than azacitidine alone, with outcomes comparable with similarly treated patients with intermediate-risk cytogenetics. Toxicities were similar in TP53mut and TP53wt patients. See related commentary by Green and Zeidner, p. 5235
Comparative histological study on the effect of tramadol abuse on the testis of juvenile and adult male albino mice

As a synthetic analog of codeine, tramadol is often prescribed to treat mild to moderate pains. This study was designed to estimate and compare the histological effect of tramadol on testes of both juvenile and adult male albino mice. A total number of 40 healthy male albino mice were classified into two main groups as follows: group I (juvenile group, includes 20 mice aged three weeks) subdivided equally into group Ia (control group received isotonic saline) and group Ib (tramadol-treated group received 40 mg/kg/d tramadol orally for 30 days); group II (adult group, includes 20 mice aged two months) subdivided equally into group IIa (control group received isotonic saline) and group IIb (tramadol-treated group). Juvenile and adult tramadol-treated groups showed numerous testicular changes, including blood vessels congestion, widening of intercellular spaces, vacuolization in interstitial tissues, luminal germ cells exfoliation, and increased expression of caspase-3 that indicated cellular apoptosis. In the ultrastructural examination, spermatogenic cells degenerated with the frequent appearance of apoptotic cells. Sertoli cells showed vacuolations, large lipid droplets, and disrupted intercellular cell junctions. These observed testicular changes were markedly observed in the juvenile group. Testicular abnormalities and apoptotic changes can be caused by tramadol administration. These abnormalities are more common in juvenile mice.
The Effects of Attention Deficit Hyperactivity Disorder and Other Psychiatric Comorbidities to Outcomes in Trauma Patients

Background Psychiatric illnesses affect outcomes in trauma. Studies have examined the relationship between depression, schizophrenia, post-traumatic stress disorder, and other mental disorders with trauma, yet few have examined attention-deficit-hyperactivity disorder (ADHD). Attention-deficit-hyperactivity disorder has been suggested to increase the risk of injury, but severity and outcomes of the injury are not frequently studied. The relationship of additional psychiatric disorders in patients with ADHD to traumatic injury was also examined in this study. Methods A 5-year retrospective analysis was performed using the trauma registry of an urban ACS verified level 1 trauma center. Patients with ADHD were separated into ADHD Only and ADHD+ (having additional psychiatric comorbidities) and compared to a matched population of non-ADHD patients and patients with non-ADHD psychiatric disorders to analyze their demographics and outcomes. Descriptive statistics were used to analyze the data as appropriate. Results Seventy-three patients with ADHD were identified, with over half having additional psychiatric comorbidities (58.9%). The majority of ADHD patients were White (54.8%) vs Black (61.6%) at admission. At admission non-ADHD patients had significantly fewer psychiatric comorbidities (11%) compared to ADHD patients (58.9%). ADHD with psychiatric comorbidities patients had significantly higher ISS and longer hospital LOS. However, GCS and ICU LOS were not different between the two groups. Conclusions Patients with ADHD were significantly more likely to have psychiatric comorbidities and experience worse outcomes compared to patients without ADHD.
Secondary Intraocular Lens Implantation (IOL) in Children- What, Why, When, and How?

ABSTRACT Purpose To provide a comprehensive review on secondary IOL implantation in children who have undergone primary surgery at an early age and are aphakic aiming at answering common dilemmas among pediatric ophthalmologists. Method of literature review A systematic literature search was done using keywords like secondary intraocular implantation, congenital cataractand surgical aphakia. Various novel case reports, retrospective case studies and review articles covering different aspects of secondary IOL implantation were searched and reviewed using PubMed and Google scholar journal search engines. Results This article highlights various aspects of secondary IOL implantation like the appropriate timing should be when the child is entering preschool, with the proper technique being in bag fixation is the most preferred method with least associated complications and the IOL type should be decided based on the fixation site. Conclusion Secondary IOL implantation can accomplish good and stable long-term outcomes in children. It is the most accepted mode of optical correction once the appropriate age is achieved.
Dynamics of a thin ﬁlm ﬂowing down a heated wall with ﬁnite thermal diﬀusivity

Consider the dynamics of a thin ﬁlm ﬂowing down a heated substrate. The substrate heating generates a temperature distribution on the free surface which in turn induces surface-tension gradients and corresponding thermocapillary stresses that aﬀect the free surface and therefore the ﬂuid ﬂow. We study here the eﬀect of ﬁnite substrate thermal diﬀusivity on the ﬁlm dynamics. Linear stability analysis of the full Navier–Stokes and heat transport equations indicates that if the substrate diﬀusivity is suﬃciently small, the ﬁlm becomes unstable at a ﬁnite wavelength and at a Reynolds number smaller than that predicted in the long-wavelength limit. This property is captured in a reduced-order system of equations derived using a weighted-residual integral-boundary-layer method. This reduced-order model is also used to compute the bifurcation diagrams of solution branches connecting the trivial ﬂat ﬁlm to traveling waves including solitary pulses. The eﬀect of ﬁnite diﬀusivity is to separate a simultaneous Hopf/transcritical bifurcation into its individual component bifurcations. The appropriate Hopf bifurcation then connects only to the solution branch of negative-hump pulses, with wave speed less than the linear wave speed while the branch of positive-single-hump pulses merges with the branch of positive-two-hump pulses at a supercritical Reynolds number. In the regime where ﬁnite-wavelength instability occurs, there exists a Hopf-bifurcation pair connected by a branch of periodic solutions, whose period cannot be increased indeﬁnitely. Numerical simulation of the reduced-order system shows the development of a train of coherent structures each of which resembles a stationary positive-hump pulse, and, in the regime of ﬁnite-wavelength instability, wavelength selection and saturation to periodic traveling waves.