Miracle-dz/UniFAR-FTUs huggingface dataset:
Durability of Cross-Protection by Different Schedules of the Bivalent HPV Vaccine: the CVT Trial.

BACKGROUND The Costa Rica HPV Vaccine Trial (CVT) has documented cross-protection of the bivalent HPV vaccine against HPV31/33/45 up to seven years after vaccination, even with one dose of the vaccine. However, the durability of such protection remains unknown. Here, we evaluate different schedules of the vaccine's efficacy against HPV31/33/45 out to 11 years post-vaccination, expanding to other non-targeted HPV types. METHODS We compared the rates of HPV infection in vaccinated women to the rates in a comparable cohort of unvaccinated women. We estimated the average vaccine efficacy (VEavg) against incident infections and tested for a change in VE over time. RESULTS Among 3-dose women, we observed statistically significant cross-protection against HPV31/33/45 (VEavg=64.4%, 95%CI: 57.7% to 70.0%). Additionally, we observed borderline, statistically significant cross-protection against HPV35 (VEavg=23.2%, 95%CI: 0.3% to 40.8%) and HPV58 (VEavg=21.2%, 95%CI: 4.2% to 35.3%). There was no decrease in VE over time (two-sided p-for-trend>0.05 for HPV31, 33, 35, 45, 58). As a benchmark, VEavg against HPV16/18 was 82.0% (95%CI: 77.3% to 85.7%). Among 1-dose women, we observed comparable efficacy against HPV31/33/45 (VEavg=54.4%, 95%CI: 21.0% to 73.7%). Acquisition of non-protected HPV types was similar between vaccinated and unvaccinated women, indicating that the difference in HPV infection rates was not attributable to differential genital HPV exposure. CONCLUSION Substantial cross-protection afforded by the bivalent vaccine against HPV31/33/45 and, to a lesser extent, HPV35 and HPV58, was sustained and remained stable after 11 years post-vaccination, reinforcing the notion that the vaccine is an effective option for protection against HPV-associated cancers.
Sex as a biological variable in the rat model of diisopropylfluorophosphate‐induced long‐term neurotoxicity

Sex differences in response to neurotoxicant exposure that initiates epileptogenesis are understudied. We used telemetry‐implanted male and female adult rats exposed to an organophosphate (OP) neurotoxicant, diisopropylflourophosphate (DFP), to test sex differences in the severity of status epilepticus (SE) and the development of spontaneous recurrent seizures (SRS). Females had significantly less severe SE and decreased epileptiform spikes compared with males, although females received a higher dose of DFP than males. The estrous stages had no impact on seizure susceptibility, but rats with severe SE had a significantly prolonged diestrus. A previously demonstrated disease‐modifying agent, an inducible nitric oxide synthase inhibitor, 1400W, was tested in both sexes. None of the eight males treated with 1400W developed convulsive SRS during 4 weeks post‐DFP exposure, while two of seven females developed convulsive SRS. Concerning gliosis and neurodegeneration, there were region‐specific differences in the interaction between sex and SE severity. As SE severity influences epileptogenesis, and as females had significantly less severe SE, sex as a biological variable should be factored into the design of future OP nerve agent experiments while evaluating neurotoxicity and optimizing potential disease‐modifying agents.
Phenotypic divergence of thermotolerance: Molecular basis and cold adaptive evolution related to intrinsic DNA flexibility of glacier-inhabiting Cryobacterium strains.

The link between GC content and thermal adaptation is controversial. Here, we compared maximum growth temperature (TMGT ) and genomics of 78 Cryobacterium strains to avoid unreliable conclusions resulting from distantly phylogenetic groups. Phylogenomic analysis revealed this taxon had much higher diversification than we knew. Interestingly, these strains showed thermotolerance divergence with phylogenetic cohesion. A significant difference was found between TMGT ≤ 20 °C strains and TMGT >20 °C strains in genomic GC content which mainly caused by variation of GC3. TMGT ≤ 20 °C strains tended to use synonymous codons ended with A/U, but TMGT > 20 °C strains tended to use G/C. Lower GC content at synonymous sites (≈GC3) of TMGT ≤ 20 °C strains could provide lower intrinsic DNA flexibility which strongly associated with optimal molecular dynamics, and then guarantee DNA function at lower growth temperatures. This analysis of codon bias revealed close relationships for thermal adaptation, GC content at synonymous sites (≈GC3), intrinsic DNA flexibility, and optimal DNA dynamics. Natural selection was main force driving this codon bias; strains with lower TMGT endured stronger natural selection. Therefore, this study provided molecular basis for bacterial adaptive evolution from moderate temperature to low temperature. This article is protected by copyright. All rights reserved.
In vivo tissue engineering of an adipose tissue flap using fat grafts and Adipogel

For decades, plastic surgeons have spent considerable effort exploring anatomical regions for free flap design. More recently, tissue‐engineering approaches have been utilised in an attempt to grow transplantable tissue flaps in vivo. The aim of this study was to engineer a fat flap with a vascular pedicle by combining autologous fat grafts and a novel acellular hydrogel (Adipogel) in an established tissue‐engineering model comprising a chamber and blood vessel loop. An arteriovenous loop was created in the rat groin from the femoral vessels and positioned inside a perforated polycarbonate chamber. In Group 1, the chamber contained minced, centrifuged autologous fat; in Group 2, Adipogel was added to the graft; and in Group 3, Adipogel alone was used. Constructs were histologically examined at 6 and 12 weeks. In all groups, new tissue was generated. Adipocytes, although appearing viable in the graft at the time of insertion, were predominantly nonviable at 6 weeks. However, by 12 weeks, new fat had formed in all groups and was significantly greater in the combined fat/Adipogel group. No significant difference was seen in final construct total volume or construct neovascularisation between the groups. This study demonstrated that a pedicled adipose flap can be generated in rats by combining a blood vessel loop, an adipogenic hydrogel, and a lipoaspirate equivalent. Success appears to be based on adipogenesis rather than on adipocyte survival, and consistent with our previous work, this adipogenesis occurred subsequent to graft death and remodelling. The regenerative process was significantly enhanced in the presence of Adipogel.
Tumour suppressor candidate 3 inhibits biological function and increases endoplasmic reticulum stress of melanoma cells WM451 by regulating AKT/GSK3‐β/β‐catenin pathway

Melanoma is a highly malignant and is a life‐threatening disease with no effective treatment currently. This study aims to evaluate the significance of TUSC3, an endoplasmic reticulum stress (ERS)‐inducible gene and explore its relationship with AKT/GSK3‐β/β‐catenin signalling pathway in melanoma cell WM451. We investigated TUSC3 expression in melanoma cell by qRT‐PCR, CCK‐8 and clonal formation assays were utilized to evaluate cell proliferation. Wound healing and transwell experiments detected cell migration and invasion. Flow cytometry detected the level of apoptosis. Western blot analysed MMP2, MMP9, p‐AKT, p‐GSK3‐β, β‐catenin and AKT, GSK3‐β, ERS‐related proteins and apoptosis‐related proteins in WM451 cells. The results revealed that TUSC3 was remarkably decreased in melanoma cell lines. Overexpression of TUSC3 significantly inhibits melanoma cell WM451 biological functions and promotes expression of ERS‐related proteins in WM451 cells, increases ERS in WM451 cells by inhibiting AKT/GSK3‐β/β‐catenin pathway. These finding suggest that TUSC3 regulates biological functions of melanoma cells WM451 and increases ERS in melanoma cells WM451 via the inhibition of the AKT/GSK3‐β/β‐catenin signalling pathway.
The SiaA/B/C/D signaling network regulates biofilm formation in Pseudomonas aeruginosa

Bacterial cyclic‐di‐GMP (c‐di‐GMP) production is associated with biofilm development and the switch from acute to chronic infections. In Pseudomonas aeruginosa, the diguanylate cyclase (DGC) SiaD and phosphatase SiaA, which are co‐transcribed as part of a siaABCD operon, are essential for cellular aggregation. However, the detailed functions of this operon and the relationships among its constituent genes are unknown. Here, we demonstrate that the siaABCD operon encodes for a signaling network that regulates SiaD enzymatic activity to control biofilm and aggregates formation. Through protein–protein interaction, SiaC promotes SiaD diguanylate cyclase activity. Biochemical and structural data revealed that SiaB is an unusual protein kinase that phosphorylates SiaC, whereas SiaA phosphatase can dephosphorylate SiaC. The phosphorylation state of SiaC is critical for its interaction with SiaD, which will switch on or off the DGC activity of SiaD and regulate c‐di‐GMP levels and subsequent virulence phenotypes. Collectively, our data provide insights into the molecular mechanisms underlying the modulation of DGC activity associated with chronic infections, which may facilitate the development of antimicrobial drugs.
A randomized clinical trial of the effects of leafy green vegetables and inorganic nitrate on blood pressure

ABSTRACT Background A diet rich in fruits and vegetables is associated with lowering of blood pressure (BP), but the nutrient(s) responsible for these effects remain unclear. Research suggests that inorganic nitrate present in leafy green vegetables is converted into NO in vivo to improve cardiovascular function. Objective In this study, we evaluated the effect of leafy green vegetables on BP in subjects with elevated BP, with the aim of elucidating if any such effect is related to their high nitrate content. Design We enrolled 243 subjects, 50–70 y old, with a clinic systolic BP (SBP) of 130–159 mm Hg. After a 2-wk run-in period on a nitrate-restricted diet the subjects were randomly assigned to receive 1 of the following 3 interventions daily for 5 wk: low-nitrate vegetables + placebo pills, low-nitrate vegetables + nitrate pills (300 mg nitrate), or leafy green vegetables containing 300 mg nitrate + placebo pills. The primary end point measure was the difference in change in 24 h ambulatory SBP between the groups. Results A total of 231 subjects (95%) completed the study. The insignificant change in ambulatory SBP (mean ± standard deviation) was −0.6 ± 6.2 mm Hg in the placebo group, −1.2 ± 6.8 mm Hg in the potassium nitrate group, and −0.5 ± 6.6 mm Hg in the leafy green vegetable group. There was no significant difference in change between the 3 groups. Conclusions A 5-wk dietary supplementation with leafy green vegetables or pills containing the same amount of inorganic nitrate does not decrease ambulatory SBP in subjects with elevated BP. This trial was registered at clinicaltrials.gov as NCT02916615.
Strain Ratio of Ultrasound Elastography for the Evaluation of Tendon Elasticity

Copyright © 2020 The Korean Society of Radiology Strain Ratio of Ultrasound Elastography for the Evaluation of Tendon Elasticity Ke-Vin Chang, MD, PhD , Wei-Ting Wu, MD, Ing-Jeng Chen, MD, Che-Yu Lin, PhD Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Bei-Hu Branch, Taipei, Taiwan; Institute of Applied Mechanics, College of Engineering, National Taiwan University, Taipei, Taiwan
Comparison of Periodization Models of Concurrent Training in Recreationally Active Postmenopausal Women

Abstract Medeiros, LHL, Sandbakk, SB, Bertazone, TMA, and Bueno Júnior, CR. Comparison of periodization models of concurrent training in recreationally active postmenopausal women. J Strength Cond Res 36(4): 977–983, 2022—Although concurrent training is the most effective way to improve both neuromuscular and cardiorespiratory functions in older populations, there are no studies in the literature comparing different periodization models on cardiorespiratory and muscle strength adaptations. Thus, the main objective of this study was to investigate the effects of different periodization models of concurrent aerobic and strength training using equalized training volume programs on muscle strength and cardiorespiratory fitness in recreationally active postmenopausal women. After 3 weeks of adaptation, 58 women aged 50–75 years were randomly assigned to (a) nonperiodization (NP), (b) daily nonlinear periodization (NLP), or (c) flexible daily NLP (FNLP). At baseline and after 12 weeks, aerobic fitness (peak oxygen uptake [V̇o2peak] and the 6-minute walk test) and maximal muscle strength (1 repetition maximum of bench press and leg press) were measured. It was shown that maximal strength increased in the bench press (effect size [ES] 1.18 in NLP and 1.22 in FNLP) and leg press (ES 0.92 in NLP and 0.89 in FNLP) in the periodized groups—in the NP group, these values were 0.49 and 0.46, respectively. In the 6-minute walk test, aerobic fitness statistically improved in all groups—with an ES of 1.02 in the NP, 1.33 in the NLP, and 0.54 in the FNLP. This study showed that only periodization models (NLP and FNLP) induced a moderate ES in maximal strength, and all groups (NP, NLP, and FNLP) demonstrated improved aerobic fitness evaluated by V̇o2peak and the 6-minute walk test in recreationally active postmenopausal women.
Diversity of bacteria in different life stages and their impact on the development and reproduction of Zeugodacus tau (Diptera: Tephritidae)

Fruit flies usually harbor diverse communities of bacteria in their digestive systems, which are known to play a significant role in their fitness. However, little information is available on Zeugodacus tau, a polyphagous pest worldwide. This study reports the first extensive analysis of bacterial communities in different life stages and their effect on the development and reproduction of laboratory‐reared Z. tau. Cultured bacteria were identified using the conventional method, and all bacteria were identified by high‐throughput technologies (16S ribosomal RNA gene sequencing of V3‒V4 region). A total of six bacterial phyla were identified in larvae, pupae, and male and female adult flies, which were distributed into 14 classes, 32 orders, 58 families and 96 genera. Proteobacteria was the most represented phylum in all the stages except larvae. Enterobacter, Klebsiella, Providencia, and Pseudomonas were identified by conventional and next‐generation sequencing analysis in both male and female adult flies, and Enterobacter was found to be the main genus. After being fed with antibiotics from the first instar larvae, bacterial diversity changed markedly in the adult stage. Untreated flies laid eggs and needed 20 days before oviposition while the treated flies showed ovary development inhibited and were not able to lay eggs, probably due to the alteration of the microbiota. These findings provide the cornerstone for unexplored research on bacterial function in Z. tau, which will help to develop an environmentally friendly management technique for this kind of harmful insect.
Designing cancer immunotherapy trials with delayed treatment effect using maximin efficiency robust statistics

The indirect mechanism of action of immunotherapy causes a delayed treatment effect, producing delayed separation of survival curves between the treatment groups, and violates the proportional hazards assumption. Therefore using the log‐rank test in immunotherapy trial design could result in a severe loss efficiency. Although few statistical methods are available for immunotherapy trial design that incorporates a delayed treatment effect, recently, Ye and Yu proposed the use of a maximin efficiency robust test (MERT) for the trial design. The MERT is a weighted log‐rank test that puts less weight on early events and full weight after the delayed period. However, the weight function of the MERT involves an unknown function that has to be estimated from historical data. Here, for simplicity, we propose the use of an approximated maximin test, the V0 test, which is the sum of the log‐rank test for the full data set and the log‐rank test for the data beyond the lag time point. The V0 test fully uses the trial data and is more efficient than the log‐rank test when lag exits with relatively little efficiency loss when no lag exists. The sample size formula for the V0 test is derived. Simulations are conducted to compare the performance of the V0 test to the existing tests. A real trial is used to illustrate cancer immunotherapy trial design with delayed treatment effect.
Personal and Clinical Factors Associated with Older Drivers’ Self-Awareness of Driving Performance

ABSTRACT Most older adults perceive themselves as good drivers; however, their perception may not be accurate, and could negatively affect their driving safety. This study examined the accuracy of older drivers’ self-awareness of driving ability in their everyday driving environment by determining the concordance between the perceived (assessed by the Perceived Driving Ability [PDA] questionnaire) and actual (assessed by electronic Driving Observation Schedule [eDOS]) driving performance. One hundred and eight older drivers (male: 67.6%; age: mean = 80.6 years, standard deviation [SD] = 4.9 years) who participated in the study were classified into three groups: underestimation (19%), accurate estimation (29%), and overestimation (53%). Using the demographic and clinical functioning information collected in the Candrive annual assessments, an ordinal regression showed that two factors were related to the accuracy of self-awareness: older drivers with better visuo-motor processing speed measured by the Trail Making Test (TMT)-A and fewer self-reported comorbid conditions tended to overestimate their driving ability, and vice versa.
Dying in the Neurointensive Care Unit After Withdrawal of Life-Sustaining Therapy: Associations of Advance Directives and Health-Care Proxies With Timing and Treatment Intensity

Background and Purpose: Critically ill patients require a careful approach for prognosis and decision-making. The German health legislation aims to strengthen the role of advance directives (ADs) and health-care proxies (HCPs). Their impact within a dedicated neurocritical care setting is unknown. This study aimed to assess the practice of withdrawal or withholding of life-sustaining therapy (WOLST) in a German neurointensive care unit (NICU) focusing on whether AD or HCP is associated with timing and treatment intensity. Methods: Data on patients who died after WOLST at a dedicated NICU of a German university hospital, from 2010 to 2013, were retrospectively analyzed. Results: Of 400 deceased patients, 310 (77.5%) died after initiation of WOLST. Among them, 68 (21.9%) were identified to have AD or HCP or both (AD + HCP). WOLST patients with AD, HCP, or AD + HCP were older than those without (median age: 77 vs 72 years, P < .001) but did not show any other distinct baseline features. There was no difference in the specific neurocritical care measures between the groups. Poisson regression analysis showed no significant difference in the probability of time-dependent WOLST initiation between those with and without AD/HCP, after adjusting for age and sex (adjusted incidence rate ratio, 1.10; 95% confidence interval, 0.94-1.28; P = .244). Conclusions: In this single-center study of mainly cerebrovascular NICU patients, AD or HCP was neither associated with an earlier WOLST nor associated with a difference in treatment intensity before WOLST. Further prospective studies should assess the emerging concept of advance care planning in neurocritical care.
Evaluation of cardiovascular risk factors in people living with HIV in São Paulo, Brazil.

INTRODUCTION HIV infection as a chronic disease has emerged from treatment advances over the past three decades. From this perspective, the diseases associated with AIDS are not a main threat for patients who use Antiretroviral Therapy (ART). A new set of HIV associated complications have emerged resulting in comorbidities related to aging and ART exposure as cardiovascular disease (CVD). This study aimed to evaluate the cardiovascular risk factors in people living with HIV (PLWH) in Brazil. METHODOLOGY This was a cross-sectional study carried out at all Specialized Care Services for people living with HIV in the Southeast of Brazil. A sociodemographic and clinical questionnaire was used and cardiovascular risk assessed through the Framingham Score. Data analysis was performed by Chi-square, Fisher's exact test and logistic regression. RESULTS The majority were male, over 40 years old and they showed a mean age of 44 years. Current hypertension, diabetes, altered body mass index, presence of metabolic syndrome and altered abdominal circumference were also associated with cardiovascular risk. After regression analysis, male sex, older age, smoking, diabetes, hypertension and metabolic syndrome were related as predictive factors for a higher cardiovascular risk. CONCLUSIONS The results demonstrate that combination of the prevention of modifiable risk factors with considerable changes in lifestyle are determining factors for success in the therapeutic of PLWH. High levels of motivation are essential for behavioral changes, and nurses are ideally position to provide safe care with nonpharmacological strategies for CVD risk reduction.
Computer-Aided Diagnosis System for the Evaluation of Thyroid Nodules on Ultrasonography: Prospective Non-Inferiority Study according to the Experience Level of Radiologists

Objective To determine whether a computer-aided diagnosis (CAD) system for the evaluation of thyroid nodules is non-inferior to radiologists with different levels of experience. Materials and Methods Patients with thyroid nodules with a decisive diagnosis of benign or malignant nodule were consecutively enrolled from November 2017 to September 2018. Three radiologists with different levels of experience (1 month, 4 years, and 7 years) in thyroid ultrasound (US) reviewed the thyroid US with and without using the CAD system. Statistical analyses included non-inferiority testing of the diagnostic accuracy for malignant thyroid nodules between the CAD system and the three radiologists with a non-inferiority margin of 10%, comparison of the diagnostic performance, and the added value of the CAD system to the radiologists. Results Altogether, 197 patients were included in the study cohort. The diagnostic accuracy of the CAD system (88.48%, 95% confidence interval [CI] = 82.65–92.53) was non-inferior to that of the radiologists with less experience (1 month and 4 year) of thyroid US (83.03%, 95% CI = 76.52–88.02; p < 0.001), whereas it was inferior to that of the experienced radiologist (7 years) (95.76%, 95% CI = 91.37–97.96; p = 0.138). The sensitivity and negative predictive value of the CAD system were significantly higher than those of the less-experienced radiologists were, whereas no significant difference was found with those of the experienced radiologist. A combination of US and the CAD system significantly improved sensitivity and negative predictive value, although the specificity and positive predictive value deteriorated for the less-experienced radiologists. Conclusion The CAD system may offer support for decision-making in the diagnosis of malignant thyroid nodules for operators who have less experience with thyroid US.