Miracle-dz/UniFAR-FTUs huggingface dataset:
Optimal timing of capsular tension ring implantation in pseudoexfoliation syndrome.

PURPOSE The aim of this study was to evaluate the appropriate timing of capsular tension ring implantation in cases of zonular weakness due to pseudoexfoliation syndrome. METHODS This prospective, comparative study was performed at the Ophthalmology Department of Inonu University, Malatya, Turkey. There were 43 patients included in the study. Group 1 (16 patients) had early capsular tension ring implantation, and group 2 (27 patients) had late capsular tension ring implantation. Patients with pseudoexfoliation syndrome who underwent phacoemulsification surgery, posterior chamber intraocular lens implantation, and capsular tension ring implantation were included in the study. Intraoperative complications and difficulties with either capsular tension ring implantation or cortex removal were evaluated in each eye. RESULTS There was no significant difference between the groups in the difficulty of capsular tension ring implantation (p=0.124). The difficulty of cortex removal differed significantly between the groups (p=0.003). Intraoperative complications were observed in 3 patients in group 1 and 11 patients in group 2; the difference between the groups was not significant (p=0.18). Posterior capsule fluctuations were observed in 8 patients (29.5%) in group 2, which resulted in posterior capsule rupture in 2 patients. CONCLUSIONS Cortex removal is more difficult with early capsular tension ring implantation, and posterior capsule fluctuations may cause problems with late capsular tension ring implantation. The surgeon must consider the risk-to-benefit ratio of early versus late insertion for the optimal timing of capsular tension ring implantation.
Synthesis of Plumbagin by the Retro-Diels-Alder Reaction

Plumbagin1 (1) is one of the alkylated naphthoquinones2) which have interesting bioactivities such as antimicrobial and antineoplastic activities. ') How ever alkylation methods to naphthoquinones have been chiefly carried out with prenyl moieties. '-e) A synthesis of plumbagin was published by Fieser and Dunn,7 but the synthetic route is disadvantageous because of the poor total yield. We now wish to report here a new alkylation method of juglone (2) by the retro-Diels-Alder reaction, and demonstrate utility of this method by the synthesis of plumbagin (1). The Diels-Alder reaction of juglone (2) with
Examining sleep deficiency and disturbance and their risk for incident dementia and all-cause mortality in older adults across 5 years in the United States

Background: Sleep disturbance and deficiency are common among older adults and have been linked with dementia and all-cause mortality. Using nationally representative data, we examine the relationship between sleep disturbance and deficiency and their risk for incident dementia and all-cause mortality among older adults. Methods: The National Health and Aging Trends Study (NHATS) is a nationally-representative longitudinal study of Medicare beneficiaries in the US age 65 and older. Surveys that assessed sleep disturbance and duration were administered at baseline. We examined the relationship between sleep disturbance and deficiency and incident dementia and all-cause mortality over the following 5 years using Cox proportional hazards modeling, controlling for confounders. Results: Among the sample (n = 2,812), very short sleep duration (≤5 hours: HR = 2.04, 95% CI: 1.26 - 3.33) and sleep latency (>30 minutes: HR = 1.45, 95% CI: 1.03 - 2.03) were associated with incident dementia in adjusted Cox models. Difficulty maintaining alertness (“Some Days”: HR = 1.49, 95% CI: 1.13 - 1.94 and “Most/Every Day”: HR = 1.65, 95% CI: 1.17 - 2.32), napping (“Some days”: HR = 1.38, 95% CI: 1.03 - 1.85; “Most/Every Day”: HR = 1.73, 95% CI: 1.29 - 2.32), sleep quality (“Poor/Very Poor”: HR = 1.75, 95% CI: 1.17 - 2.61), and very short sleep duration (≤5 hours: HR = 2.38, 95% CI: 1.44 - 3.92) were associated with all-cause mortality in adjusted Cox models. Conclusions: Addressing sleep disturbance and deficiency may have a positive impact on risk for incident dementia and all-cause mortality among older adults.
Identifying Opioid Withdrawal Using Wearable Biosensors

Wearable biosensors can be used to monitor opioid use, a problem of dire societal consequence given the current opioid epidemic in the US. Such surveillance can prompt interventions that promote behavioral change. Prior work has focused on the use of wearable biosensor data to detect opioid use. In this work, we present a method that uses machine learning to identify opioid withdrawal using data collected with a wearable biosensor. Our method involves developing a set of machine-learning classifiers, and then evaluating those classifiers using unseen test data. An analysis of the best performing model (based on the Random Forest algorithm) produced a receiver operating characteristic (ROC) area under the curve (AUC) of 0.9997 using completely unseen test data. Further, the model is able to detect withdrawal with just one minute of biosensor data. These results show the viability of using machine learning for opioid withdrawal detection. To our knowledge, the proposed method for identifying opioid withdrawal in OUD patients is the first of its kind.
Accelerated Clearance and Degradation of Cell-Free HIV by Neutralizing Antibodies Occurs via FcγRIIb on Liver Sinusoidal Endothelial Cells by Endocytosis

Key Points Neutralizing Ab-opsonized HIV was cleared faster from blood circulation than HIV. FcγRIIb, the lone FcγR expressed in human LSEC, clears Ab-HIV via endocytosis. Endocytosed Ab-HIV localizes to lysosomes of LSEC. Neutralizing Abs suppress HIV infection by accelerating viral clearance from blood circulation in addition to neutralization. The elimination mechanism is largely unknown. We determined that human liver sinusoidal endothelial cells (LSEC) express FcγRIIb as the lone Fcγ receptor, and using humanized FcγRIIb mouse, we found that Ab-opsonized HIV pseudoviruses were cleared considerably faster from circulation than HIV by LSEC FcγRIIb. Compared with humanized FcγRIIb-expressing mice, HIV clearance was significantly slower in FcγRIIb knockout mice. Interestingly, a pentamix of neutralizing Abs cleared HIV faster compared with hyperimmune anti-HIV Ig (HIVIG), although the HIV Ab/Ag ratio was higher in immune complexes made of HIVIG and HIV than pentamix and HIV. The effector mechanism of LSEC FcγRIIb was identified to be endocytosis. Once endocytosed, both Ab-opsonized HIV pseudoviruses and HIV localized to lysosomes. This suggests that clearance of HIV, endocytosis, and lysosomal trafficking within LSEC occur sequentially and that the clearance rate may influence downstream events. Most importantly, we have identified LSEC FcγRIIb-mediated endocytosis to be the Fc effector mechanism to eliminate cell-free HIV by Abs, which could inform development of HIV vaccine and Ab therapy.
Isotemporal Substitution of Time Between Sleep and Physical Activity: Associations With Cardiovascular Risk Factors in Early Rheumatoid Arthritis

We aimed to determine relationships between objectively measured nightly sleep, sedentary behavior (SB), light physical activity (LPA), and moderate to vigorous physical activity (MVPA) with risk factors for cardiovascular disease (CVD) in patients with early rheumatoid arthritis (RA). Furthermore, we aimed to estimate consequences for these risk factors of theoretical displacements of 30 minutes per day in one behavior with the same duration of time in another.
Effects of shockwave therapy on pain and disability in individuals with rotator cuff tendinopathy: a systematic review protocol.

OBJECTIVE The objective of this study is to systematically review randomized controlled trials comparing the effect of shockwave therapy with other forms of interventions on pain and disability in individuals with rotator cuff tendinopathy. INTRODUCTION Shoulder pain is a common musculoskeletal complaint in which rotator cuff tendons are usually affected. Shockwave therapy is a novel conservative treatment option for rotator cuff-related shoulder pain. A systematic review in 2004 reported conflicting results on the effectiveness of shockwave therapy in treating chronic rotator cuff tendonitis, whereby it is effective for calcific rotator cuff tendonitis but not for non-calcific ones. Hence, it is timely to review this topic with the addition of results from studies published since 2004. INCLUSION CRITERIA This review will consider randomized controlled trials that have evaluated shockwave therapy delivered via radial or focused extracorporeal means in individuals with rotator cuff tendinopathy without restrictions of race, gender, and age. Studies comparing individuals receiving shockwave therapy of varying dosages will be excluded in this review. METHODS A three-step search strategy will be used to locate studies published in English from databases. No search restrictions were applied regarding the year of publication. Study selection, assessment of methodological quality, and data extraction will be conducted by two independent reviewers. Data will be pooled in statistical meta-analysis, where possible. A funnel plot will be generated to detect any potential publication bias. The quality of the evidence will be analyzed using the Grading of Recommendations, Assessment, Development and Evaluation approach. SYSTEMATIC REVIEW REGISTRATION NUMBER PROSPERO CRD42020160166.
Contributions of the Human Cytomegalovirus UL30-Associated Open Reading Frames to Infection

Viral genes and their products are the critical determinants of viral infection. Human cytomegalovirus (HCMV) encodes many gene products whose roles during viral infection have not been assessed. Elucidation of the contributions that various HCMV gene products make to infection provides insight into the infectious program, which could potentially be used to limit HCMV-associated morbidity, a major issue during congenital infection and in immunosuppressed populations. ABSTRACT Transposon-based insertional mutagenesis screens have assessed how disruption of numerous human cytomegalovirus (HCMV) open reading frames (ORFs) impacts in vitro viral replication. Insertional mutagenesis of the HCMV UL30 gene was previously found to substantially inhibit production of viral progeny. However, there are a number of putative UL30-associated ORFs, and it is unclear how they impact viral replication. Here, we report on the contributions of the eight UL30-associated ORFs to infection. We find that deletion of the canonically annotated UL30 ORF substantially reduces production of infectious virus at both high and low multiplicities of infection (MOI). This deletion likely has complex effects on viral replication, as we find that it reduces the expression of neighboring non-UL30-associated ORFs. Mutation of the initiating methionine of the canonical UL30 ORF indicated that it is dispensable for high- and low-MOI infection in the highly passaged AD169 strain, although it is important for low-MOI infection in the less-passaged TB40/E strain. Comutation of eight methionines in the UL30 region results in a low-MOI viral replication defect, as does mutation of the TATA box responsible for the most abundant UL30 transcript, which is found to be necessary for the accumulation of multiple UL30-associated protein isoforms during infection. In total, our data indicate the importance of the UL30-associated ORFs during low-MOI HCMV infection and further highlight the difficulty associated with the functional interrogation of broadly disruptive mutations: e.g., large deletions or transposon insertions. IMPORTANCE Viral genes and their products are the critical determinants of viral infection. Human cytomegalovirus (HCMV) encodes many gene products whose roles during viral infection have not been assessed. Elucidation of the contributions that various HCMV gene products make to infection provides insight into the infectious program, which could potentially be used to limit HCMV-associated morbidity, a major issue during congenital infection and in immunosuppressed populations. Here, we explored the role of HCMV’s UL30-associated gene products and found that they are important for HCMV replication. Future work elucidating the mechanisms through which they contribute to viral infection could highlight novel avenues for therapeutic intervention.
In vivo and in vitro cell based model of lung adenocarcinoma from patients with pleural effusion.

Lung adenocarcinoma (LAC) is a common and aggressive form of lung cancer that is increasing in incidence among never smokers at younger age. Current treatment of patients with LAC is insufficient and there is a need for identification of effective biomarkers and development of therapy targets. These demands require also improved models for in vivo and in vitro experimentation. In this study, we describe the establishment of two LAC cell lines, termed LuCa-3 and LuCa-6. Both were derived from pleural effusion (PE) cells of LAC patients (L3 and L6) and both are readily propagated as tumor xenografts in immune-deficient mice. PE cells from the patient L6 exhibited also capacity for in vitro growth and were cultured in two forms: (i) as a suspension growing cell population, termed LuCa-6S, composed of non-clumping single cells; and (ii) as a monolayer-like culture, labeled LuCa-6A, exhibiting tight cell-to-cell and to culture surface adherence. Unique features of these two sublines and their cell clones are the capacity to convert from a non-clumping single-cell suspension into the adherent growth pattern and vice versa. Immunostaining of patients' tumor tissue xenografts and cultured subline cells displayed markers specific for the phenotype of human LAC. LuCa-6S and LuCa-6A cells did not reveal a noticeable disparity in quantitative growth characteristics. However, a number of differences were detected between these two cell populations manifested in detection or intensities of antigen expressions on cell surface (CD133, SFTPC) and in the nucleus (TTF-1) including pluripotent (OCT-4, SOX-2, NANOG) genes in cancer stem-like cells (CSCs). Dissimilarities between these two sublines were also detected in N-glycan profiles and in the sensitivity to natural killer cells. Salient features of these subline cell populations are responsiveness to selective upregulation of the pluripotent genes in subsets of CSCs via conversion of their growth patterns and/or by using culture stem media with growth factors. The described in vivo/in vitro model enables broader experimental approaches in studies of lung adenocarcinoma.
Discovery of a Major QTL Controlling Trichome IV Density in Tomato Using K-Seq Genotyping

Trichomes are a common morphological defense against pests, in particular, type IV glandular trichomes have been associated with resistance against different invertebrates. Cultivated tomatoes usually lack or have a very low density of type IV trichomes. Therefore, for sustainable management of this crop, breeding programs could incorporate some natural defense mechanisms, such as those afforded by trichomes, present in certain Solanum species. We have identified a S. pimpinellifolium accession with very high density of this type of trichomes. This accession was crossed with a S. lycopersicum var. cerasiforme and a S. lycopersicum var. lycopersicum accessions, and the two resulting F2 populations have been characterized and genotyped using a new genotyping methodology, K-seq. We have been able to build an ultra-dense genetic map with 147,326 SNP markers with an average distance between markers of 0.2 cm that has allowed us to perform a detailed mapping. We have used two different families and two different approaches, QTL mapping and QTL-seq, to identify several QTLs implicated in the control of trichome type IV developed in this accession on the chromosomes 5, 6, 9 and 11. The QTL located on chromosome 9 is a major QTL that has not been previously reported in S. pimpinellifolium. This QTL could be easily introgressed in cultivated tomato due to the close genetic relationship between both species.
“I just stand around and look friendly” – Comparing medical students’ and physicians’ ward round scripts

Abstract Background Even though ward rounds are important learning opportunities for medical students, unfavourable ward round scripts of students and physicians may hinder learning in such situations. We investigated medical students’ and physicians’ ward round scripts with respect to (a) the content focus of ward round activities, and (b) the potential of these activities for knowledge construction. Methods We conducted standardized interviews with 50 medical students and physicians in internal medicine at different expertise stages. Activities participants labelled as typical for ward rounds were coded with respect to their content focus and their potential with regard to knowledge construction. Results Regarding content focus, especially residents mainly named activities bound to patient care. Teaching- and learning-related activities were very rare, but more frequently mentioned by students and more experienced physicians. With respect to potential for knowledge construction, students regarded significantly more passive activities (= low potential for knowledge construction) as typical for ward rounds, especially when they described their own role. Conclusions Medical students should be supported in their development of conceiving ward rounds as valuable learning opportunities. Residents should be asked to take their teaching responsibility seriously, for example by demanding an active engagement of the students during ward rounds.
Characterization of DtrJ as an IncC plasmid conjugative DNA transfer component

Incompatibility group C (IncC) plasmids are large (50–400 kb), broad host range plasmids that drive the spread of genes conferring resistance to all classes of antibiotics, most notably the blaNDM gene that confers resistance to last‐line carbapenems and the mcr‐3 gene that confers resistance to colistin. Several recent studies have improved our understanding of the basic biological mechanisms driving the success of IncC, in particular the identification of multiple novel IncC conjugation genes by transposon directed insertion‐site sequencing. Here, one of these genes, dtrJ, was examined in further detail. The dtrJ gene is located in the DNA transfer locus on the IncC backbone, and quantitative reverse‐transcriptase PCR analysis revealed it is transcribed in the same operon as the DNA transfer genes traI and traD (encoding the relaxase and coupling protein, respectively) and activated by the AcaDC regulatory complex. We confirmed that DtrJ is not required for pilus biogenesis or mate pair formation. Instead, DtrJ localizes to the membrane, where it interacts with the coupling protein TraD and functions as an IncC DNA transfer protein. Overall, this work has defined the role of DtrJ in DNA transfer of IncC plasmids during conjugation.
Reduced Nucleoprotein Availability Impairs Negative-Sense RNA Virus Replication and Promotes Host Recognition

Negative-sense RNA viruses comprise some of the most important known human pathogens, including influenza A virus, measles virus, and Ebola virus. These viruses possess RNA genomes that are unreadable to the host, as they require specific viral RNA-dependent RNA polymerases in conjunction with other viral proteins, such as nucleoprotein, to be replicated and transcribed. ABSTRACT Negative-sense RNA viruses (NSVs) rely on prepackaged viral RNA-dependent RNA polymerases (RdRp) to replicate and transcribe their viral genomes. Their replication machinery consists of an RdRp bound to viral RNA which is wound around a nucleoprotein (NP) scaffold, forming a viral ribonucleoprotein complex. NSV NP is known to regulate transcription and replication of genomic RNA; however, its role in maintaining and protecting the viral genetic material is unknown. Here, we exploited host microRNA expression to target NP of influenza A virus and Sendai virus to ascertain how this would impact genomic levels and the host response to infection. We find that in addition to inducing a drastic decrease in genome replication, the antiviral host response in the absence of NP is dramatically enhanced. Additionally, our data show that insufficient levels of NP prevent the replication machinery of these NSVs to process full-length genomes, resulting in aberrant replication products which form pathogen-associated molecular patterns in the process. These dynamics facilitate immune recognition by cellular pattern recognition receptors leading to a strong host antiviral response. Moreover, we observe that the consequences of limiting NP levels are universal among NSVs, including Ebola virus, Lassa virus, and measles virus. Overall, these results provide new insights into viral genome replication of negative-sense RNA viruses and highlight novel avenues for developing effective antiviral strategies, adjuvants, and/or live-attenuated vaccines. IMPORTANCE Negative-sense RNA viruses comprise some of the most important known human pathogens, including influenza A virus, measles virus, and Ebola virus. These viruses possess RNA genomes that are unreadable to the host, as they require specific viral RNA-dependent RNA polymerases in conjunction with other viral proteins, such as nucleoprotein, to be replicated and transcribed. As this process generates a significant amount of pathogen-associated molecular patterns, this phylum of viruses can result in a robust induction of the intrinsic host cellular response. To circumvent these defenses, these viruses form tightly regulated ribonucleoprotein replication complexes in order to protect their genomes from detection and to prevent excessive aberrant replication. Here, we demonstrate the balance that negative-sense RNA viruses must achieve both to replicate efficiently and to avoid induction of the host defenses.
Immune responses and viral persistence in SHIV.C.CH848-infected rhesus macaques.

Chimeric simian/human immunodeficiency viruses (SHIVs) are widely used in nonhuman primate models to recapitulate HIV infection in humans, yet most SHIVs fail to establish persistent viral infection. We investigated immunological and virological events in rhesus macaques infected with the newly developed SHIV.C. CH848, combined with antiretroviral therapy (cART). Similar to HIV/SIV infection, SHIV.C. CH848 infection established viral reservoirs in CD4+ T cells and myeloid cells, accompanied by productive infection and depletion of CD4+ T cells in systemic and lymphoid tissues throughout SHIV infection. Despite 6-months of cART suppressed viral replication, integrated proviral DNA levels remained stable, especially in CD4+ T cells, and the viral rebound was also observed after ART interruption. Autologous neutralizing antibodies to the parental HIV-1 strain CH848 were detected, with limited viral evolution at 5 months post infection. In comparison, heterogenous neutralizing antibodies in SHIV.C. CH848-infected macaques were not detected except for one (1 of 10) animal at 2 years post infection. These findings suggest that the SHIV.C. CH848, a novel class of transmitted/founder SHIVs, can establish sustained viremia and viral reservoirs in rhesus macaques with clinical immunodeficiency consequences, providing a valuable SHIV model for HIV research.Importance SHIVs have been extensively used in a nonhuman primate (NHP) model for HIV research. Here, we investigate viral reservoir in tissues and immune responses in an NHP model inoculated with newly generated transmitted/founder HIV-1 clade C-based SHIV.C. CH848. The data show T/F SHIVC infection of macaques more closely recapitulates the virologic and clinical features of HIV infection including persistent viremia, and viral rebound once antiretroviral therapy is discontinued. These results suggest this CCR5-tropic, SHIVC virus is valuable for testing responses to HIV vaccines and therapeutics.