Miracle-dz/UniFAR-FTUs huggingface dataset:
Vaccine safety issues at the turn of the 21st century

Global gains in vaccination coverage during the early 21st century have been threatened by the emergence of antivaccination groups that have questioned the effectiveness of vaccines to generate public distrust of vaccines and immunisation programmes. This manuscript summarises six key topics that have been at the centre of global discussions on vaccine safety during the early 21st century: thiomersal in multi-dose non-live vaccines, aluminium adjuvants used with several non-live vaccines, autism and auto-immune conditions as possible consequences of vaccination, a risk of immune overload with increasing numbers of vaccinations, and detrimental non-specific effects (NSEs) of vaccination. For each topic, we describe the hypothesis behind the public concern, the evidence reviewed by the WHO’s Global Advisory Committee for Vaccine Safety (GACVS) during 1999–2019, and any significant new data that has emerged since GACVS conclusions were made. Although the scientific evidence on these issues overwhelmingly supports the safety of vaccines, communication messages to caregivers and providers need to condense and convey scientific information in an appropriate way to address concerns contributing to vaccine distrust. In addition, there is need for further studies specifically designed to address both positive and negative NSE of vaccination. The role of GACVS will be increasingly important in evaluating the evidence and engaging the global community in promoting and assuring the safety of vaccines in the decades to come as we move into an era in which we use new vaccination platforms, antigens and formulations.
Calcaneotibial screws for immobilisation of the tarsocrural joint of dogs in extension: effect of the angle of screw placement on the force to failure in a canine cadaveric model

ABSTRACT Aims To compare the force to failure under axial loading of a calcaneotibial screw placed approximately perpendicular to the tibia with that of a screw placed perpendicular to the calcaneus, when used to immobilise the tarsus in an ex vivo canine model. Methods Twelve pairs of cadaveric hindlimbs from large breed dogs, without orthopaedic or soft tissue disease, were prepared by transecting the limb at the level of the stifle and stripping the limbs of all musculature from the stifle to mid-metatarsus, including removal of the common calcaneal tendon from all limbs. The limbs in each pair were randomly assigned to receive a calcaneotibial screw placed perpendicular to the long axis of either the calcaneus (C group) or the tibia (T group) with the tarsus in full extension. The distal limb was potted in resin and the proximal tibia was pinned to allow biomechanical testing in compressive loading. Testing was performed to apply an axial load using a material testing machine in a proximodistal direction through the tibia, advancing at a rate of 10 mm/second. The force to failure was recorded in kN and compared between groups. Results The median force to failure of the C group was 0.86 (min 0.50; max 1.64) kN which was higher than the T group which had a median force to failure of 0.74 (min 0.26, max1.05) kN (p = 0.004). All modes of failure were by screw pull-out. Conclusions A calcaneotibial screw placed at an angle approximately perpendicular to the long axis of the calcaneus, has a higher force to failure under axial loading than a calcaneotibial screw that is placed at an angle approximately perpendicular to the tibia, in a canine cadaveric model. Clinical relevance A temporary calcaneotibial screw is a common method of immobilising the tarsus in extension to protect primary repair of a common calcaneal tendon injury. Placing a calcaneotibial screw perpendicular to the calcaneus may be a more reliable option for immobilisation of the tarsus to protect a common calcaneal tendon repair compared to screws placed perpendicular to the tibia. However extrapolation of these results into a clinical setting requires caution.
Ultrafast electron crystallography studies of charge-density waves materials and nanoscale ice

ULTRAFAST ELECTRON CRYSTALLOGRAPHY STUDIES OF CHARGE-DENSITY WAVES MATERALS AND NANOSCALE ICE By Tzong-Ru Terry Han The main focus of this dissertation is centered around the study of structural dynamics and phase transition in charge-density wave (CDW) materials. Due to their quasi-reduced dimensionality, a CDW presents a unique system to study the interplay between electron and lattice, effect of symmetry breaking, and electronic condensates. Femtosecond time-resolved pump-probe technique with electron crystallography offers the perfect tool to disentangle the two main players in CDW: electrons and ions. By illumination with intense femtosecond optical pulses to increase the electron energy, we monitor how the energy flows to other subsystems, and explore regions of the energy landscape that are not accessible through conventional methods. Taking advantages of the uniaxial CDW formation of CeTe3 that allows us to differentiate nonCDW-related contributions to the lattice response, we isolate the CDW-related structural response from the thermal effects on lattice. From the two-component structural dynamics, we examine how strongly the electron and lattice couple to each other, and further distinguish the internal energy transfer between each charge and lattice subsystems. From this CeTe3 experiment, we provide an explanation to a signature phenomenon belonging to "classical Peierls" CDW systems. Compared to the classical CDW in CeTe3, 1T-TaS2 is at the other end of spectrum with its well decorated phase diagram including almost all flavors of CDW, Mott insulating, and superconducting states. Utilizing femtosecond photo-doping, we explore the energy landscape for states or phases that are not accessible by other conventional means, like chemical doping and pressure induced modification. The remaining part of this dissertation presents the journey we embarked on when trying to unveil the mystery of water, the ubiquitous molecule that sustains life on earth. Utilizing water delivery system designed specifically for our ultra-high-vacuum chamber, we explore the structural change near the water phase boundary and carrier redistribution or diffusion at the water/nanoparticle/silicon interface.
Do the 2013 United States Preventive Services Task Force guidelines for lung cancer screening fail high-risk African American smokers? An institutional retrospective observational cohort study

Background Lung cancer cause nearly 1.76 million deaths worldwide in 2018. In 2011, the National-Lung-Cancer-Screening-Trial showed 20% relative risk reduction with LDCT and subsequently led to the current USPSTF screening guidelines. However, the predominant focus on elderly, Caucasian questions its generalizability to communities with young, African Americans such as our institution. Hence, the objective of our study is to investigate the need to modify the current screening guidelines at our institution by assessing the applicability of newer individual risk-based prediction models for LDCT screening. Methods This is a retrospective observational cohort study of newly diagnosed lung cancer patients at LSU Health Sciences Center Shreveport from 2011 to 2015. One-third of the patients did not meet the current USPSTF screening guidelines. We categorized them into high-risk (groups1 and 2), moderate-risk, and low-risk according to 2018 NCCN Lung Cancer Screening Guidelines Version 1.2020. The high-risk groups were differentiated using the Tammemagi lung cancer risk calculator. Results Among those who did not meet the screening guidelines, nearly 50% were African American, 95% with known smoking history, and 80% diagnosed at advanced stage at the time of diagnosis. After employing the Tammemagi Risk based calculator, 12.5% were categorized into high-risk group 2, who are also eligible for annual LDCT. Conclusion The current USPSTF guidelines have failed in our population consisting of young African American smokers, questioning the health disparity in medicine. By employing individual risk-based prediction models, we could potentially identify tailored high-risk populations leading to appropriate use of LDCT screening.
Exogenous orexin A down-regulates luteinizing hormone secretory activity in prepubertal female rats.

INTRODUCTION Orexin A is a neuropeptide synthesized in the lateral hypothalamus. Orexin A immunoreactive fibers overlap distribution with GnRH neurons. In adult rats, orexin A is known to affect LH secretion via GnRH release modulation. Since data concerning orexin A impact on the hypothalamo-pituitary axis activity are limited, we focused on orexin A and receptors of NPY involvement in the modulation of LH release and LH subunit β mRNA expression in prepubertal female rats. MATERIAL AND METHODS Forty immature female Wistar rats were divided into four groups and received two intracerebroventricular (icv) microinjections of 1. artificial cerebrospinal fluid - CSF (controls) 2. CSF followed by orexin A; 3. Selective NPY receptor antagonist (BIBP) followed by CSF; 4. BIBP followed by orexin A. One hour after the last microinjection, all rats were decapitated. Trunk blood was collected and serum was stored at -20°C for the LH RIA examination. The adenohypophysis was immediately excised, flash-frozen, and kept at -80°C for RNA extraction. Real-time PCR amplification was carried out and relative LHβ gene expression was calculated. RESULTS In comparison to the CSF-treated controls with mean LH serum concentration of 0.40±0.02 ng/ml, mean LH serum level was diminished both after orexin A (0.27±0.01 ng/ml) or BIBP (0.30±0.02 ng/ml), icv microinjections. In the presence of BIBP, orexin A more effectively inhibited LH release (0.20±0.01 ng/ml) when compared to the BIBP-treated group. Orexin A and BIBP exerted a consistent inhibitory effect on Lhb mRNA expression levels in the anterior pituitary gland. In comparison to the CSF-treated controls, orexin A and BIBP-treated females responded with, respectively, 35% and 40% reduction of Lhb mRNA expression. Orexin A and BIBP co-administration evoked a further reduction of LHβ gene transcriptional activity. CONCLUSIONS Orexin A exerts a down-regulatory effect on LH synthesis and release in immature female rats. Considering that Y1R-oriented down-regulation of endogenous NPY activity did not reverse the suppressive effect of exogenous orexin A, it might be suggested that NPY and orexin A systems can operate independently to affect gonadotropin activity in the anterior pituitary of the immature female rats.
Multisensory enhancement of overt behavior requires multisensory experience

The superior colliculus (SC) is richly endowed with neurons that integrate cues from different senses to enhance their physiological responses and the overt behaviors they mediate. However, in the absence of experience with cross‐modal combinations (e.g., visual–auditory), they fail to develop this characteristic multisensory capability: Their multisensory responses are no greater than their most effective unisensory responses. Presumably, this impairment in neural development would be reflected as corresponding impairments in SC‐mediated behavioral capabilities such as detection and localization performance. Here, we tested that assumption directly in cats raised to adulthood in darkness. They, along with a normally reared cohort, were trained to approach brief visual or auditory stimuli. The animals were then tested with these stimuli individually and in combination under ambient light conditions consistent with their rearing conditions and home environment as well as under the opposite lighting condition. As expected, normally reared animals detected and localized the cross‐modal combinations significantly better than their individual component stimuli. However, dark‐reared animals showed significant defects in multisensory detection and localization performance. The results indicate that a physiological impairment in single multisensory SC neurons is predictive of an impairment in overt multisensory behaviors.
Seagrasses in an era of ocean warming: a review

Seagrasses are valuable sources of food and habitat for marine life and are one of Earth's most efficient carbon sinks. However, they are facing a global decline due to ocean warming and eutrophication. In the last decade, with the advent of new technology and molecular advances, there has been a dramatic increase in the number of studies focusing on the effects of ocean warming on seagrasses. Here, we provide a comprehensive review of the future of seagrasses in an era of ocean warming. We have gathered information from published studies to identify potential commonalities in the effects of warming and the responses of seagrasses across four distinct levels: molecular, biochemical/physiological, morphological/population, and ecosystem/planetary. To date, we know that although warming strongly affects seagrasses at all four levels, seagrass responses diverge amongst species, populations, and over depths. Furthermore, warming alters seagrass distribution causing massive die‐offs in some seagrass populations, whilst also causing tropicalization and migration of temperate species. In this review, we evaluate the combined effects of ocean warming with other environmental stressors and emphasize the need for multiple‐stressor studies to provide a deeper understanding of seagrass resilience. We conclude by discussing the most significant knowledge gaps and future directions for seagrass research.
SpRY Cas9 Can Utilize a Variety of Protospacer Adjacent Motif Site Sequences To Edit the Candida albicans Genome

Genetic modification of the human fungal pathogen Candida albicans allows us to better understand how fungi differ from humans at the molecular level and play essential roles in the therapeutic development. CRISPR/Cas9-mediated genome editing systems can be used to introduce site-specific mutations to C. albicans. ABSTRACT Candida albicans is a human fungal pathogen capable of causing life-threatening infections. The ability to edit the C. albicans genome using CRISPR/Cas9 is an important tool investigators can leverage in their search for novel therapeutic targets. However, wild-type Cas9 requires an NGG protospacer adjacent motif (PAM), leaving many AT-rich regions of DNA inaccessible. A recently described near-PAMless CRISPR system that utilizes the SpRY Cas9 variant can target non-NGG PAM sequences. Using this system as a model, we developed C. albicans CRISPR/SpRY. We tested our system by mutating C. albicans ADE2 and show that CRISPR/SpRY can utilize non-NGG PAM sequences in C. albicans. Our CRISPR/SpRY system will allow researchers to efficiently modify C. albicans DNA that lacks NGG PAM sequences. IMPORTANCE Genetic modification of the human fungal pathogen Candida albicans allows us to better understand how fungi differ from humans at the molecular level and play essential roles in the development of therapeutics. CRISPR/Cas9-mediated genome editing systems can be used to introduce site-specific mutations to C. albicans. However, wild-type Cas9 is limited by the requirement of an NGG PAM site. CRISPR/SpRY targets a variety of different PAM sequences. We modified the C. albicans CRISPR/Cas9 system using the CRISPR/SpRY as a guide. We tested CRISPR/SpRY on C. albicans ADE2 and show that our SpRY system can facilitate genome editing independent of an NGG PAM sequence, thus allowing the investigator to target AT-rich sequences. Our system will potentially enable mutation of the 125 C. albicans genes which have been previously untargetable with CRISPR/Cas9. Additionally, our system will allow for precise targeting of many genomic locations that lack NGG PAM sites.
Engineering the Deformability of Albumin‐Stabilized Emulsions for Lymph‐Node Vaccine Delivery

A major challenge in vaccine delivery is to achieve robust lymph‐node (LN) accumulation, which can capitalize on concentrated immunocytes and cytokines in LNs to stimulate the onset and persistence of adaptive immune responses. Previous attempts at developing vaccine delivery systems have focused on the sizes, charges, or surface ligands but not on their deformability. In fact, the LN homing of antigen‐presenting cells depends on deformability to pass through the cellular gaps. Herein, the deformability of albumin‐stabilized emulsions is engineered. Owing to self‐adaptive deformability, the droplets (≈330 nm) can attach to and deform between cells and adjust their sizes to pass through the endothelial gaps (20–100 nm), favoring direct LN transfer (intercellular pathway). Additionally, owing to relatively large sizes, some emulsions can be retained at the administration sites for potent antigen uptake and activation of APCs as well as LN‐targeted delivery of vaccines (intracellular pathway). Compared with solid particles, the dual LN transfer strategy evidently enhances antigen accumulation and activation of LN drainage, potently stimulates cellular immune responses, and increases the survival rate of tumor‐bearing mice. Thus, the deformability of albumin‐stabilized droplets may offer an efficient strategy for potent LN targeting and enhanced vaccinations.
Genital Human Papillomavirus Prevalence Over the Lifespan Among Females and Males in a National Cross-Sectional Survey, United States, 2013–2016

Sex differences in patterns of human papillomavirus (HPV) prevalence by age were observed for quadrivalent vaccine-type HPV and non–vaccine-type HPV. Patterns differed between vaccine-type and non–vaccine-type HPV prevalence suggesting vaccine impact. Supplemental digital content is available in the text. Background Patterns of human papillomavirus (HPV) prevalence by age differ by sex. To further the descriptive epidemiology of genital HPV, we analyzed prevalence by age for nonvaccine (non–4vHPV) type and vaccine (4vHPV) type HPV by sex using 2013–2016 National Health and Nutrition Examination Survey data, the first 4 years of national data from both sexes. Methods Penile and cervicovaginal swabs were self-collected from 15- to 59-year-olds and tested for 37 HPV types. The 4vHPV-type (6/11/16/18) and non–4vHPV-type (any of 33 other types) prevalences were estimated by 3-year age group and participant characteristics. Average percent changes (APCs) in prevalence were estimated using segmented log-binomial regression. Results Among females, a positive relationship between non–4vHPV-type prevalence and age was seen from 15–17 to 21–23 years (APC, 56.5), followed by a negative relationship through 30–32 years (APC, −13.2); thereafter, prevalence was not related to age. The 4vHPV-type prevalence was positively related to age through 24–26 years (APC, 56.9), then negatively related through 57–59 years (APC, −6.0). Among males, non–4vHPV-type prevalence had a positive relationship with age through 21–23 years (APC, 102.4) with a smaller positive relationship through 57–59 years (APC, 1.4). For both sexes, modeled joinpoints for 4vHPV-type prevalence occurred at older ages compared with joinpoints for non–4vHPV-type prevalence. Conclusions Sex differences in age-specific non–vaccine-type HPV prevalence may reflect natural history and sexual behavior. Differences in vaccine-type and non–vaccine-type modeling results suggest vaccine impact as joinpoints occur in mid-late 20s for vaccine-type HPV but early 20s for nonvaccine types. These data can assist in refining HPV vaccination models and inform HPV vaccination practices and policy.
RSV attenuates epithelial cell restitution by inhibiting actin cytoskeleton-dependent cell migration

The airway epithelium’s ability to repair itself after injury, known as epithelial restitution, is an essential mechanism enabling the respiratory tract’s normal functions. Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections worldwide. We sought to determine whether RSV delays the airway epithelium wound repair process both in vitro and in vivo. We found that RSV infection attenuated epithelial cell migration, a step in wound repair, promoted stress fiber formation, and mediated assembly of large focal adhesions. Inhibition of Rho-associated kinase, a master regulator of actin function, reversed these effects. There was increased RhoA and phospho-myosin light chain 2 following RSV infection. In vivo, mice were intraperitoneally inoculated with naphthalene to induce lung injury, followed by RSV infection. RSV infection delayed reepithelialization. There were increased concentrations of phospho-myosin light chain 2 in day 7 naphthalene + RSV animals, which normalized by day 14. This study suggests a key mechanism by which RSV infection delays wound healing.
Serum calcium improved systemic inflammation marker for predicting survival outcome in rectal cancer.

Background Systemic inflammation markers have shown prognostic values with variability in rectal cancer. Considering the association of serum calcium with inflammation, we aimed to examine whether it could improve systemic inflammation markers for survival prediction. Methods We enrolled 508 patients with stage I to III rectal cancer who underwent curative resection. The cohort was grouped by corrected serum calcium (cCa), platelet-to-lymphocyte ratio (PLR), and CaPLR (a score model combining cCa with PLR) for survival analysis. The LR (likelihood ratio) test and AIC (Akaike information criterion) were applied to compare models in survival prediction. The primary endpoint was disease-free survival (DFS). Results A total of 26.7% (136/508) patients reached recurrence after curative surgery. Both high cCa (HR 1.486; 95% CI, 1.018-2.171; P=0.040) and high PLR (HR 1.452; 95% CI, 1.059-1.991; P=0.021) were significantly associated with worse DFS. In model comparison, the AIC and LR were improved after cCa was added to PLR model in DFS prediction (AIC: 1,704.83 vs. 1,707.14 vs. 1,707.15; LR: 8.68 vs. 4.37 vs. 4.36; P=0.037). The CaPLR was developed for DFS prediction with adjusted HRs of 2.216 (95% CI, 1.256-3.909; P=0.006) and 1.679 (95% CI, 1.004-2.836; P=0.047) for high and intermediate score group respectively compared to low score group. A nomogram for predicting DFS was generated by using CaPLR and other clinical predictors, with a concordance index of 0.705 (95% CI, 0.620-0.789; P<0.001). Conclusions Serum calcium could improve systemic inflammation markers in survival prediction for patients with rectal cancer.