Miracle-dz/UniFAR-FTUs huggingface dataset:
Thirty Year Projected Magnitude (to 2050) of Near and Distance Vision Impairment and the Economic Impact if Existing Solutions are Implemented Globally

ABSTRACT Purpose: Recent global, regional and country-level prevalence estimates for blindness and vision impairment will be important when designing future public health policies. The aim of this paper is to contribute to this discussion by estimating the productivity impact of known effective interventions to treat all preventable cases of vision impairment at the global, regional and country-level up to 2050. We also provide estimates of potential reduction in the number of people with vision impairment, as well as averted vision-impaired years up to 2050. Methods: We combined recent estimates of the prevalence of blindness, distance and near vision impairment with the World Bank’s World Development Indicators (WDI) and estimated the global, regional and country-level productivity gains up to 2030, 2040 and 2050 from known effective interventions, primarily cataract surgery and treated uncorrected refractive errors. The magnitude of productivity gains relative to baseline depended on population size, estimated current and future prevalence of vision impairment, level of economic development, long-term wage growth, and long-term real interest rates. Results: Globally, we estimate that the number of people affected by blindness could be reduced from the estimated 114.6 million by 2050 to 58.3 million. This would be associated with over one billion blind life-years averted and US$ 984 billion in global productivity gains. These numbers are dwarfed by the impact of interventions to reduce the prevalence of Moderate and Severe Vision Impairment (MSVI) [Presenting Acuity <20/60 to 20/400 in the better-seeing eye]. We estimate that the number of people affected by MSVI could be reduced by 435.8 million people to 147.9 million by 2050. This reduction would translate to over 9 billion MSVI -life-years avoided and US$ 17 trillion in productivity gains by 2050. While other causes of VI would not be possible to eliminate completely based on current known effective treatments, low-cost interventions to eliminate VI from uncorrected presbyopia would avert 1.2 billion presbyopia life-years and achieve US$ 1.05 trillion in productivity gains by 2050. In total, the global productivity gains for all three categories are estimated to be US$ 19 trillion by 2050. East Asia makes up the greatest share of productivity gains due to the high number of people affected by VI and the region’s continuing economic growth. Conclusion: Implementation of currently known and effective treatments of avoidable blindness, MSVI and presbyopia would be expected to contribute significant productivity gains to the global economy at a fraction of the estimated costs to deliver them.
Frontalis Linkage Without Intraoperative Eyelid Elevation for the Management of Myopathic Ptosis

Purpose: To report the effect of frontalis linkage without intraoperative eyelid elevation for the management of myopathic ptosis. Methods: Retrospective analysis of 21 (42 eyelids) myopathic patients with bilateral ptosis who were operated between 1999 and 2017. All patients had orbicularis weakness and poor or absent Bell’s phenomenon. Surgery consisted of using an autogenous fascia sling to link the tarsal plate to the frontalis muscle without any degree of intraoperative eyelid elevation. The main outcome measures were margin reflex distance, brow height and degree of brow excursion and degree of lagophthalmos, and exposure keratitis. Results: After surgery, there were significant changes (p <0.0001) in both margin reflex distance and brow position. Mean margin reflex distance increased to 1.4 mm ± 1.34 DP and with full frontalis contraction, it reached 3.0 mm ± 1.73 DP, while mean brow position decreased 1.6 mm ± 1.59 SD, p < 0.0001. Postoperative lagophthalmos was not detected in 31 (74%) eyes. In the remaining 11 eyes (26%), lagophthalmos ranged from 1.2 to 5.2 mm (mean = 1.7 mm ± 0.74 DP). Mild inferior superficial keratitis was detected in 14 eyes (33.3%) of 7 patients only 3 of which had lagophthalmos. One patient needed additional surgery to correct unilateral eyelid retraction. Overall, 81.81% of the patients were pleased with the procedure. Conclusions: Myopathic ptosis can be alleviated with a minimal amount of lagophthalmos by just linking the tarsal plate to the frontalis muscle without lifting the eyelid margin intraoperatively. Frontalis linkage without intraoperative eyelid elevation allows upper eyelid ptosis repair in myopathic patients with a low rate of complications.
An educational intervention to improve attitudes regarding HPV vaccination and comfort with counseling among US medical students

ABSTRACT Many medical students are not comfortable recommending the human papillomavirus (HPV) vaccine because they do not feel prepared to discuss it with their patients. A prior study demonstrated that this is particularly a problem among unvaccinated students. Our purpose was to determine if medical student attitudes and comfort with counseling could be improved by attending a single lecture delivered by an expert on the topic. To assess the effects of the educational program, we conducted pre- and posttests on medical students before and after a single lecture on HPV vaccination. Changes in items related to attitude and comfort were examined. Student characteristics associated with changes in scores were also examined and compared. A total of 256 medical students participated in the pre- and posttests. Before the lecture, students demonstrated low knowledge of HPV vaccination and did not feel comfortable counseling parents of younger patients. However, students <30 years of age demonstrated significant improvements after the lecture in comfort. Asian and Hispanic students showed the greatest improvement in comfort with counseling, as did students who reported they had not received the HPV vaccine. Attending a single lecture given by an expert can improve medical students’ attitudes and comfort with HPV vaccine counseling, especially if the students were not vaccinated themselves. This study suggests that including material on HPV vaccination in the standard medical student curriculum could help increase physician recommendation for the HPV vaccine.
Platelet-Rich Plasma as Adjuvant Therapy for Recurrent Vesicovaginal Fistula: A Prospective Case Series

Vesicovaginal fistula (VVF) is the nonphysiological communication between the bladder and vagina, and surgical closure is the gold treatment standard. Despite that successful closure occurs in around 85% of patients after the first repair, recurrence remains a highly distressing complication for patients and surgeons. The aim of our study was to evaluate the efficacy of a platelet-rich plasma (PRP) injection as a supportive treatment in the surgical repair of recurrent VVF. Between January 2018 and July 2019, 16 patients with recurrent VVF were injected with PRP in a tertiary gynecological department. Subsequently, a surgical Latzko procedure for VVF closure was scheduled 6–8 weeks after the PRP injection allowing proper neovascularization and remodeling of surrounding tissues. Patients were considered cured if no leakage was observed after surgery and negative dye test results were indicated at follow-up. All patients who were examined therein remained dry. To the best of our knowledge, this is the first study aiming to assess PRP injections as a supporting treatment prior to surgical procedure for recurrent VVF. Preliminary results are encouraging, and we incorporated this method in our clinical practice. Further reports on a larger group will follow.
An Ancient Mutation in the TPH1 Gene is Consistent with the Changes in Mammalian Reproductive Rhythm

The reproductive rhythm undergoes several changes during the evolution of mammals to adapt to local environmental changes. Although the critical roles of melatonin (MLT) in the formation of reproductive rhythm have been well established, the genetic basis for the changes of reproductive rhythm remains uncertain. Here, we constructed the phylogenetic trees of 13 melatonin synthesis, metabolism and receptor genes, estimated their divergence times, and calculated their selection pressures. Then, we evaluated the effect of positively selected and functionally related mutations on protein activity. Our results showed that there were significant positive selection sites in the three major genes, including tryptophan hydroxylase 1 (TPH1), tryptophan hydroxylase 2 (TPH2) and indoleamine-2,3-dioxygenase 1 (IDO1) that are involved in melatonin synthesis, metabolism and function. At the protein level, amino acids at the 442nd site of TPH1 protein and the 194th, 286th, 315th and 404th sites of IDO1 protein were under positive selection, and the variants of the amino acid in these sites might lead to the changes in protein function. Remarkably, the 442nd site of these positive selection sites is in the tetramerization domain of TPH1 protein, and it is proline or leucine. At this site, 89.5% of the amino acid of non-seasonal reproducing mammals was proline, while that of 88.9% of seasonal reproducing mammals was leucine. This variation of the amino acid was derived from the T/C polymorphism at the 1325th site of the TPH1 gene coding sequence, which significantly altered the TPH1 activity (p < 0.01). Interestingly, the predicted age of the allele C in the mammalian genome appeared about 126.6 million years ago, and allele T appeared about 212.6 million years ago, indicating that the evolution of the TPH1 gene was affected by the two mammalian split events and the K-T extinction event. In conclusion, the T/C polymorphism at the 1325th site in the TPH1 gene coding sequence altered TPH1 activity, suggesting that this polymorphism is consistent with the reproductive rhythm of mammals.
Neer Type-II Distal Clavicle Fractures: A Cost-Effectiveness Analysis of Fixation Techniques.

BACKGROUND Neer type-II distal clavicle fractures are unstable and are generally appropriately managed with operative fixation. Fixation options include locking plates, hook plates, and suture button devices. No consensus on optimal technique exists. METHODS A decision tree model was created describing fixation of Neer type-II fractures using hook plates, locking plates, or suture buttons. Outcomes included uneventful healing, symptomatic implant removal, deep infection requiring debridement, and nonunion requiring revision. Weighted averages derived from a systematic review were used for probabilities. Cost-effectiveness was evaluated by calculating incremental cost-effectiveness ratios (ICERs). The ICER is defined as the ratio of the difference in cost and difference in effectiveness of each strategy, and is measured in cost per quality-adjusted life year (QALY). The model was evaluated using thresholds of $50,000/QALY and $100,000/QALY. Sensitivity analysis was performed on all outcome probabilities for each fixation strategy to assess cost-effectiveness across a range of values. RESULTS Forty-three papers met final inclusion criteria. Using suture buttons as the reference case in the health-care cost model, suture button repair was dominant (both less expensive and clinically superior). Hook plates cost substantially more ($5,360.52) compared with suture buttons and locking plates ($3,713.50 and $4,007.44, respectively). Suture buttons and locking plates yielded similar clinical outcomes (0.92 and 0.91 QALY, respectively). Suture button dominance persisted in the societal perspective model. Sensitivity analysis on outcome probabilities showed that locking plates became the most cost-effective strategy if the revision rate after their use was lowered to 2.2%, from the overall average in the sources of >19%. No other changes in outcome probabilities for any of the 3 techniques allowed suture buttons to be surpassed as the most cost-effective. CONCLUSIONS The cost-effectiveness of suture buttons is driven by low revision rates and high uneventful healing rates. Similar QALY values for locking plate and suture button fixation were observed, which is consistent with existing literature that has failed to identify either as the clinically superior technique. Cost-effectiveness should fit prominently into the decision-making rubric for these injuries. LEVEL OF EVIDENCE Economic Level IV. See Instructions for Authors for a complete description of levels of evidence.
g: The bedrock of skill acquisition, competence, and capacity for cognitive complexity in leader and leadership development

Intelligence (also known as general mental ability or g), as an explanatory construct, has been somewhat ignored in the study of human development in general and in leader development in particular. Studies of intelligence reveal it to be a strong predictor of academic, career, and life success. Researchers in the past have shown that intelligence also plays a role in predicting leadership emergence and effectiveness. Leader development, however, since it is properly nested in developmental (and organizational) psychology, tends to elicit the use of models and social processes to explain how leaders develop. In contrast, intelligence researchers have traditionally taken an individual differences approach. Evidence is herein presented which supports the validity of intelligence as a psychological scientific construct and demonstrates its association with academic, occupational, and life achievement. Then, in more speculative fashion, the literature dealing with leadership and leader development is explained, culminating in suggestions for a research agenda.
Overexpression of Banana ATG8f Modulates Drought Stress Resistance in Arabidopsis

Autophagy is essential for plant growth, development, and stress resistance. However, the involvement of banana autophagy-related genes in drought stress response and the underlying mechanism remain elusive. In this study, we found that the transcripts of 10 banana ATG8s responded to drought stress in different ways, and MaATG8f with the highest transcript in response to drought stress among them was chosen for functional analysis. Overexpression of MaATG8f improved drought stress resistance in Arabidopsis, with lower malonaldehyde level and higher level of assimilation rate. On the one hand, overexpression of MaATG8f activated the activities of superoxide dismutase, catalase, and peroxidase under drought stress conditions, so as to regulate reactive oxygen species accumulation. On the other hand, MaATG8f-overexpressing lines exhibited higher endogenous abscisic acid (ABA) level and more sensitivity to abscisic acid. Notably, the autophagosomes as visualized by CaMV35S::GFP–MaATG8f was activated after ABA treatment. Taken together, overexpression of MaATG8f positively regulated plant drought stress resistance through modulating reactive oxygen species metabolism, abscisic acid biosynthesis, and autophagic activity.
Permafrost Deformation Monitoring Along the Qinghai-Tibet Plateau Engineering Corridor Using InSAR Observations with Multi-Sensor SAR Datasets from 1997–2018

As the highest elevation permafrost region in the world, the Qinghai-Tibet Plateau (QTP) permafrost is quickly degrading due to global warming, climate change and human activities. The Qinghai-Tibet Engineering Corridor (QTEC), located in the QTP tundra, is of growing interest due to the increased infrastructure development in the remote QTP area. The ground, including the embankment of permafrost engineering, is prone to instability, primarily due to the seasonal freezing and thawing cycles and increase in human activities. In this study, we used ERS-1 (1997–1999), ENVISAT (2004–2010) and Sentinel-1A (2015–2018) images to assess the ground deformation along QTEC using time-series InSAR. We present a piecewise deformation model including periodic deformation related to seasonal components and interannual linear subsidence trends was presented. Analysis of the ERS-1 result show ground deformation along QTEC ranged from −5 to +5 mm/year during the 1997–1999 observation period. For the ENVISAT and Sentinel-1A results, the estimated deformation rate ranged from −20 to +10 mm/year. Throughout the whole observation period, most of the QTEC appeared to be stable. Significant ground deformation was detected in three sections of the corridor in the Sentinel-1A results. An analysis of the distribution of the thaw slumping region in the Tuotuohe area reveals that ground deformation was associated with the development of thaw slumps in one of the three sections. This research indicates that the InSAR technique could be crucial for monitoring the ground deformation along QTEC.
Antibody Responses to Immunization With HCV Envelope Glycoproteins as a Baseline for B cell-Based Vaccine Development.

BACKGROUND & AIMS We investigated antibody responses to hepatitis C virus (HCV) antigens E1 and E2 and the relevance of animal models for vaccine development. We compared antibody responses to vaccination with recombinant E1E2 complex in heathy volunteers, non-human primates (NHPs), and mice METHODS: We analyzed 519 serum samples from participants in a phase 1 vaccine trial (NCT00500747) and compared them with serum or plasma samples from C57BL/6J mice (n=28) and rhesus macaques (n=4) immunized with the same HCV E1E2 antigen. Blood samples were collected at different timepoints and analyzed for antibody binding, neutralizing activity, and epitope specificity. Monoclonal antibodies from the immunized NHPs were isolated from single plasmablasts and memory B cells, and their immunogenetic properties were characterized. RESULTS Antibody responses of the volunteers, NHPs, and mice, to the non-neutralizing epitopes on the E1 N-terminus and E2 hypervariable region 1 did not differ significantly. Antibodies from volunteers and NHPs that neutralized heterologous strains of HCV primarily interacted with epitopes in the antigen region 3. However, the neutralizing antibodies were not produced in sufficient levels for broad neutralization of diverse HCV isolates. Broadly neutralizing antibodies similar to the human VH1-69 class antibody specific for antigen region 3 were produced in the immunized NHPs. CONCLUSIONS In an analysis of vaccinated volunteers, NHPs, and mice, we found that recombinant E1E2 vaccine antigen induces high-antibody titers that are insufficient to neutralize diverse HCV isolates. Antibodies from volunteers and NHPs bind to the same neutralizing epitopes for virus neutralization. NHPs can therefore be used as a preclinical model to develop HCV vaccines. These findings also provide useful baseline values for development of vaccines designed to induce production of neutralizing antibodies.
Cumulative Sociodemographic Risk Indicators for Difficult Child Temperament

Abstract Cumulative risk models provide a convenient, parsimonious way to identify outcomes associated with multiple, highly correlated risk factors. In this paper, we explored linkages between a cumulative sociodemographic risk index, which included rurality status, and aspects of temperamental difficulty in an early school age sample of 53 school-aged children from Southcentral Appalachia. Cumulative risk was significantly predictive of temperamental difficulty, as defined by high negative affectivity and low effortful control, but post-hoc analyses revealed this association to be driven primarily by two of the eight risk indicators: rural status and income-to-needs risk. Although rurality status was highly correlated with income-to-needs risk, rurality predicted negative affectivity over and above income-to-needs risk and income-to-needs risk predicted effortful control over and above rurality status. Future models of cumulative risk may benefit from including rurality status as a risk indicator, despite high collinearity with income-to-needs risk.
D-loop Mutations in Renal Cell Carcinoma Improve Predictive Accuracy for Cancer-Related Death by Integrating with Mutations in the NADH Dehydrogenase Subunit 1 Gene

Renal cell carcinoma (RCC) is associated with various genetic alterations. Although whole-genome/exome sequencing analysis has revealed that nuclear genome alterations are associated with clinical outcomes, the association between nucleotide alterations in the mitochondrial genome and RCC clinical outcomes remains unclear. In this study, we analyzed somatic mutations in the mitochondrial D-loop region, using RCC samples from 61 consecutive patients with localized RCC. Moreover, we analyzed the relationship between D-loop mutations and NADH dehydrogenase subunit 1 (MT-ND1) mutations, which we previously found to be associated with clinical outcomes in localized RCC. Among the 61 localized RCCs, 34 patients (55.7%) had at least one mitochondrial D-loop mutation. The number of D-loop mutations was associated with larger tumor diameter (>32 mm) and higher nuclear grade (≥ISUP grade 3). Moreover, patients with D-loop mutations showed no differences in cancer-specific survival when compared with patients without D-loop mutations. However, the co-occurrence of D-loop and MT-ND1 mutations improved the predictive accuracy of cancer-related deaths among our cohort, increasing the concordance index (C-index) from 0.757 to 0.810. Thus, we found that D-loop mutations are associated with adverse pathological features in localized RCC and may improve predictive accuracy for cancer-specific deaths when combined with MT-ND1 mutations.
C5aR agonist enhances phagocytosis of fibrillar and non-fibrillar Aβ amyloid and preserves memory in a mouse model of familial Alzheimer’s disease

According to the amyloid hypothesis of Alzheimer’s disease (AD) the deposition of prefibrillar and fibrillar Aβ peptide sets off the pathogenic cascades of neuroinflammation and neurodegeneration that lead to synaptic and neuronal loss resulting in cognitive decline. Various approaches to reduce amyloid load by reducing production of the Aβ peptide or enhancing amyloid clearance by primary or secondary immunization have not proven successful in clinical trials. Interfering with the normal function of secretases and suboptimal timing of Aβ peptide removal have been put forward as possible explanations. Complement, an innate component of the immune system, has been found to modulate disease pathology and in particular neuronal loss in the AD mouse model but its mechanism of action is complex. C1Q has been shown to facilitate phagocytosis of Aβ peptide but its Ablation attenuates neuroinflammation. Experiments in AD mouse models show that inhibition of complement component C5a reduces amyloid deposition and alleviates neuroinflammation. Phagocytes including microglia, monocytes and neutrophils carry C5a receptors. Here, a widely used mouse model of AD, 5XFAD, was intermittently treated with the oral C5a receptor agonist EP67 and several neuronal and neuroinflammatory markers as well as memory function were assessed. EP67 treatment enhanced phagocytosis, resulting in a significant reduction of both fibrillar and non-fibrillar Aβ, reduced astrocytosis and preserved synaptic and neuronal markers as well as memory function. Timely and phasic recruitment of the innate immune system offers a new therapeutic avenue of treating pre-symptomatic Alzheimer disease.