Miracle-dz/UniFAR-FTUs huggingface dataset:
A 2-fold Approach to Polyoma Virus (BK) Nephropathy in Kidney Transplants: Distinguishing Direct Virus Effects From Cognate T Cell–mediated Inflammation

Supplemental Digital Content is available in the text. Background. BK nephropathy (BKN) in kidney transplants diagnosed by histology is challenging because it involves damage from both virus activity and cognate T cell–mediated inflammation, directed against alloantigens (rejection) or viral antigens. The present study of indication biopsies from the Integrated Diagnostic System in the International Collaborative Microarray Study Extension study measured major capsid viral protein 2 (VP2) mRNA to assess virus activity and a T cell–mediated rejection (TCMR) classifier to assess cognate T cell–mediated inflammation. Methods. Biopsies were assessed by local standard-of-care histology and by genome-wide microarrays and Molecular Microscope Diagnostic System (MMDx) algorithms to detect rejection and injury. In a subset of 102 biopsies (50 BKN and 52 BKN-negative biopsies with various abnormalities), we measured VP2 transcripts by real-time polymerase chain reaction. Results. BKN was diagnosed in 55 of 1679 biopsies; 30 had cognate T cell–mediated activity assessed by by MMDx and TCMR lesions, but only 3 of 30 were histologically diagnosed as TCMR. We developed a BKN probability classifier that predicted histologic BKN (area under the curve = 0.82). Virus activity (VP2 expression) was highly selective for BKN (area under the curve = 0.94) and correlated with acute injury, atrophy–fibrosis, macrophage activation, and the BKN classifier, but not with the TCMR classifier. BKN with molecular TCMR had more tubulitis and inflammation than BKN without molecular TCMR. In 5 BKN cases with second biopsies, VP2 mRNA decreased in second biopsies, whereas in 4 of 5 TCMR classifiers, scores increased. Genes and pathways associated with BKN and VP2 mRNA were similar, reflecting injury, inflammation, and macrophage activation but none was selective for BKN. Conclusions. Risk–benefit decisions in BKN may be assisted by quantitative assessment of the 2 major pathologic processes, virus activity and cognate T cell–mediated inflammation.
Validating the bifactor structure of the Ruminative Thought Style Questionnaire—A psychometric study

The Ruminative Thought Style Questionnaire (RTSQ) is a self-report measure that aims to capture rumination globally, unbiased by depressive symptoms. We explored its psychometric properties among university students (N = 1123), as the existing models about the factor structure of the RTSQ have been inconclusive. In a second study (N = 320) we tested its convergent validity compared to the Ruminative Response Scale (RRS) and its construct validity compared to the Zung Self-rating Depression Scale (ZSDS). The results of Study 1 suggest that the factor structure of the RTSQ is best described with a 19-item bifactor Exploratory Structural Equation Modelling (ESEM), where most of the variance is explained by the general factor. The model was found to be invariant across genders. The correlations in Study 2 demonstrated that the RTSQ is congruent with the RRS, and that rumination captured by the RTSQ is rather maladaptive, as it was more strongly associated with the brooding subscale of the RRS than with reflective pondering. Significant positive associations were found with depressive symptoms, reaffirming the validity of the RTSQ due to the well-known association between rumination and depressive symptoms. Our results support that RTSQ assesses rumination globally, and it is a valid measure of ruminative thinking style that is rather negatively valenced but does not solely focus on depressive mood and symptoms.
Adolescent Health Series: HPV infection and vaccination in sub‐Saharan Africa: 10 years of research in Tanzanian female adolescents ‐ narrative review

Cervical cancer is the leading cause of cancer‐related morbidity and mortality in many sub‐Saharan African (SSA) countries, including Tanzania. Most cervical cancer cases worldwide are attributable to infection of the cervix with Human Papillomavirus (HPV), a vaccine‐preventable sexually transmitted infection (STI). Over the past 10 years, we have conducted a programme of HPV research in pre‐adolescents and adolescents in Mwanza, the second‐largest city in Tanzania, which is situated in a malaria‐endemic region. In this narrative review article, we summarise the contribution of our work, alongside work of others, to improve the understanding of HPV epidemiology in SSA and development of setting‐appropriate, evidence‐based intervention strategies. We present evidence for very high prevalence and incidence of HPV infection among female SSA adolescents around the time of sexual debut, describe risk factors for HPV acquisition, and discuss associations between HPV, HIV and other STIs, which are also highly prevalent within this population. We summarise findings from early clinical trials of HPV vaccines in SSA, the first of which was an immunogenicity and safety trial conducted in Mwanza, Tanzania, and Dakar, Senegal. Within the trial, we evaluated for the first time the potential impact of malaria and helminth infection on vaccine‐induced antibody responses in Tanzanian girls. We describe research evaluating optimal HPV vaccine delivery strategies within this setting, perceived requirements for and barriers to vaccine implementation among key informants from LMIC, vaccine acceptability among girls and parents, and opportunities for co‐delivery of interventions alongside HPV vaccination to an adolescent population. Finally, we discuss country‐level barriers to vaccine uptake in LMIC, and ongoing studies in Tanzania and other SSA countries of reduced‐dose HPV vaccination schedules that may alleviate cost and logistical barriers to vaccine implementation.
FLOT-regimen Chemotherapy and Transthoracic en bloc Resection for Esophageal and Junctional Adenocarcinoma

Background and Aims: The FLOT4-AIO trial established the FLOT regimen as a compelling option for gastric, junctional and esophageal adenocarcinoma. Data on FLOT with en-bloc transthoracic esophagectomy (TTE) are limited. This study explored operative complications, tolerance, toxicity, physiological impact, and oncologic outcomes. Study design: An observational cohort study on consecutive patients at 3 tertiary centers undergoing FLOT and TTE. Toxicity, operative complications (per ECCG definitions), tumor regression grade (TRG), recurrences and survival were documented, as well as pre and post FLOT assessment of sarcopenia and pulmonary physiology. Results: 175 patients (cT2-4a, Nany) commenced treatment, 84% male, median age 65, 94% cT3/T4a, 73% cN+. 89% completed 4 preoperative cycles, and 35% all cycles. Grade 3/4 toxicities included neutropenia (12%), diarrhoea (13%), and infection (15%). Sarcopenia increased from 18% to 37% (P = 0.020), and diffusion capacity (DLCO) decreased by 8% (-34% + 25%; P < 0.010). On pathology, ypT3/4 was 59%, and ypN+54%, with 10% TRG 1, 14% TRG 2, and 76% TRG3-5, and R0 95%. 161 underwent TTE, with an in-hospital mortality of 0.6%, 24%-pneumonia, 11%-anastomotic leak, and Clavien Dindo ≥III in 27%. At a median follow up of 12 months (1-85), 33 relapsed, 8 (5%) locally, and 3yr survival was 60%. Conclusion: FLOT and en bloc TTE was safe, with no discernible impact on operative complications, with 24% having a major pathologic response. Caveats include a limited pathologic response in the majority, and negative impact on muscle mass and lung physiology, and low use of adjuvant cycles. These data may provide a real-world benchmark for this complex care pathway.
The C‐terminally shortened analogs of a hexapeptide derived from Lingzhi hydrolysate with enhanced tyrosinase‐inhibitory activity

Ganoderma lucidum or Lingzhi (Chinese) is a medicinal fungus widely used in traditional medicine as a health supplement. This study was conducted to identify an approach to enhance the anti‐tyrosinase activity of a peptide from G. lucidum by chemical modification of its C‐terminus. The original peptide was obtained from protease‐digested Lingzhi proteins, followed by ultrafiltration (molecular weight cut‐off 3 kDa) and C18 solid‐phase extraction. The hexapeptide (NH2–VLTCGF–COOH) possessing the anti‐tyrosinase activity was identified by liquid chromatography–tandem mass spectrometry (LC‐MS/MS). This hexapeptide was subjected to shortening to enhance the anti‐tyrosinase activity. Both the original peptide and the shortened peptides were synthesized by solid‐phase peptide synthesis. The purity and mass of the synthetic peptide and the modified peptide were evaluated by high‐performance liquid chromatography and LC‐MS, respectively. Comparison of the tyrosinase activities showed that the modified peptide demonstrated more than 23.27 ± 1.07% activity, which was better than that of the hexapeptide. The structure‐related biological activity was explained by molecular docking, wherein the VLT–tyrosinase complex showed two interaction forces: Asn260 and Gly281 through H‐bonding and Glu256 through electrostatic interaction. This information could help toward gaining further understanding of the correlation between the anti‐tyrosinase activity and the molecular structure of the modified hexapeptide and support its potential use as a safe cosmetic ingredient with tyrosinase‐suppressing ability.
Digital support tools for fertility patients – a narrative systematic review

Abstract Digital support tools, including smartphone apps, are increasingly being used alongside fertility treatments. These tools aim to harness the power of information and technology to improve care, facilitate communication and support patients through stressful treatment cycles. To warrant patient engagement, digital support tools must be perceived as useful. This review identifies and narratively analyses tools developed for fertility patients to date, discusses salient included features and evaluates user reviews. A systematic search of the app markets and electronic literature databases identified 46 digital support tools for fertility patients. The identified web-based tools focussed on psychosocial support, whereas the smartphone apps primarily have practical features, with some incorporating coping support. User feedback was collated from the Google and Apple app marketplaces and analysed using thematic analysis. Patients have high expectations of support apps, in particular the user experience. Nine published studies of web-based digital support tools were identified, but there was a complete absence of peer-reviewed studies of smartphone support apps for fertility patients. This review identifies the increasing range of available digital tools to support patients having fertility treatments and highlights the very limited evidence on which clinicians and patients can currently evaluate these tools.
Cf‐02, a novel benzamide‐linked small molecule, blunts NF‐κB activation and NLRP3 inflammasome assembly and improves acute onset of accelerated and severe lupus nephritis in mice

In the present study, acute onset of severe lupus nephritis was successfully treated in mice using a new, benzamide‐linked, small molecule that targets immune modulation and the NLRP3 inflammasome. Specifically, 6‐(2,4‐difluorophenyl)‐3‐(3‐(trifluoromethyl)phenyl)‐2H‐benzo[e][1,3]oxazine‐2,4(3H)‐dione (Cf‐02) (a) reduced serum levels of IgG anti‐dsDNA, IL‐1β, IL‐6, and TNF‐α, (b) inhibited activation of dendritic cells and differentially regulated T cell functions, and (c) suppressed the NF‐κB/NLRP3 inflammasome axis, targeting priming and activating signals of the inflammasome. Moreover, treatment with Cf‐02 significantly inhibited secretion of IL‐1β in lipopolysaccharide‐stimulated macrophages, but this effect was abolished by autophagy induction. These results recommend Cf‐02 as a promising drug candidate for the serious renal conditions associated with systemic lupus erythematosus. Future investigations should examine whether Cf‐02 may also be therapeutic in other types of chronic kidney disease involving NLRP3 inflammasome‐driven signaling.
Effects of human footprint and biophysical factors on the body‐size structure of fished marine species

Marine fisheries in coastal ecosystems in many areas of the world have historically removed large‐bodied individuals, potentially impairing ecosystem functioning and the long‐term sustainability of fish populations. Reporting on size‐based indicators that link to food‐web structure can contribute to ecosystem‐based management, but the application of these indicators over large (cross‐ecosystem) geographical scales has been limited to either fisheries‐dependent catch data or diver‐based methods restricted to shallow waters (<20 m) that can misrepresent the abundance of large‐bodied fished species. We obtained data on the body‐size structure of 82 recreationally or commercially targeted marine demersal teleosts from 2904 deployments of baited remote underwater stereo‐video (stereo‐BRUV). Sampling was at up to 50 m depth and covered approximately 10,000 km of the continental shelf of Australia. Seascape relief, water depth, and human gravity (i.e., a proxy of human impacts) were the strongest predictors of the probability of occurrence of large fishes and the abundance of fishes above the minimum legal size of capture. No‐take marine reserves had a positive effect on the abundance of fishes above legal size, although the effect varied across species groups. In contrast, sublegal fishes were best predicted by gradients in sea surface temperature (mean and variance). In areas of low human impact, large fishes were about three times more likely to be encountered and fishes of legal size were approximately five times more abundant. For conspicuous species groups with contrasting habitat, environmental, and biogeographic affinities, abundance of legal‐size fishes typically declined as human impact increased. Our large‐scale quantitative analyses highlight the combined importance of seascape complexity, regions with low human footprint, and no‐take marine reserves in protecting large‐bodied fishes across a broad range of species and ecosystem configurations.
Oxidative stress in the skin: Impact and related protection

Skin, our first interface to the external environment, is subjected to oxidative stress caused by a variety of factors such as solar ultraviolet, infrared and visible light, environmental pollution, including ozone and particulate matters, and psychological stress. Excessive reactive species, including reactive oxygen species and reactive nitrogen species, exacerbate skin pigmentation and aging, which further lead to skin tone unevenness, pigmentary disorder, skin roughness and wrinkles. Besides these, skin microbiota are also a very important factor ensuring the proper functions of skin. While environmental factors such as UV and pollutants impact skin microbiota compositions, skin dysbiosis results in various skin conditions. In this review, we summarize the generation of oxidative stress from exogenous and endogenous sources. We further introduce current knowledge on the possible roles of oxidative stress in skin pigmentation and aging, specifically with emphasis on oxidative stress and skin pigmentation. Meanwhile, we summarize the science and rationale of using three well‐known antioxidants, namely vitamin C, resveratrol and ferulic acid, in the treatment of hyperpigmentation. Finally, we discuss the strategy for preventing oxidative stress‐induced skin pigmentation and aging.
Factors Associated With Colorectal Cancer Screening Among First-Degree Relatives of Patients With Colorectal Cancer in China

Background First-degree relatives of patients with colorectal cancer have an elevated risk of colorectal cancer. However, the behavior and factors potential influencing first-degree relatives regarding colorectal cancer screening in China remain unknown. Objective The aim of this study was to explore the screening behavior and related factors of first-degree relatives of colorectal cancer patients. Methods A cross-sectional design was applied, and 201 first-degree relatives participated from August 2018 to July 2019. Data were collected about demographic information, the “Colorectal Cancer Perceptions Scale,” and screening behavior of first-degree relatives. Factors associated with screening behavior were identified using logistic regression analysis. Results Only 18.9% of first-degree relatives had participated in colonoscopy screening. Two Health Belief Model factors were the influencing factors of their participation in colorectal cancer screening. Higher possibility of colorectal cancer screening of first-degree relatives was associated with higher perceived susceptibility (odds ratio, 1.224; 95% confidence interval, 1.075–1.395) and lower perception of barriers (odds ratio, 0.880; 95% confidence interval, 0.820–0.944) of first-degree relatives. Conclusions Participation in colorectal cancer screening by first-degree relatives requires improvement; perceived susceptibility and perception of barriers were the most important predictors. Implications for Practice Health professionals can enhance awareness of colorectal cancer susceptibility and address barriers to colorectal cancer screening among first-degree relatives at both individual and social levels.
Qualifying Exam Syllabus Proposal

Convex polytopes are the sets of feasible solutions to linear programs. The combinatorics and geometry of polytopes are essential to understanding the efficiency of algorithms that solve these classical optimization problems. In particular, the graph (or 1-skeleton) of a polytope is intimately connected to Dantzig’s simplex family of methods for solving linear programs. When the iterative method is implemented on a computer, ambiguities in the procedure are resolved by the specification of a pivot rule. Bounding the diameters of the graphs of polytopes is particularly interesting since the diameter of its graph is a lower bound on the number of iterations required for the simplex method using any pivot rule. Let n be a fixed positive integer. A halfspace H is a set of the form H := {x ∈ R | 〈α, x〉 ≤ a} for some a ∈ R and a non-zero vector α ∈ Rn. The boundary ∂H of a halfspace H forms a hyperplane, which can be described as follows: ∂H := {x ∈ R | 〈α, x〉 = a} A polytope P in Rn is the bounded intersection of finitely-many halfspaces. For a subset K ⊆ Rn, we define the convex hull conv K to be the smallest convex set containing K. Then, we can give an equivalent definition for a polytope: A subset P ⊆ Rn is a polytope if
Balancing Stability and Stiffness Through Optimization of Parallel Compliance

Having a wide range of achievable stiffness is essential for a robotic manipulator to robustly and safely interact with unknown environments. However, the achievable controller stiffness is fundamentally bounded by the system’s passive stiffness, which introduces problems for compliant robots with series elasticity. Since strong passive stiffness is undesirable in uncertain environments, we introduce coupled tendon routing (CTR) along with nonlinear parallel compliance (NPC) to effectively shift this boundary with minimal change to the overall stiffness. In this paper, we present a novel method for optimization and physical implementation to systematically determine the nonlinear parallel compliance to meet stability goals and further reduce the overall stiffness through coupled tendon routing. Experiments are carried out with two tendon-driven 2-DOF planar fingers to demonstrate and validate the effectiveness of the proposed method.
Cell and Intra-Cell Dynamics IV LIMITS ON INFORMATION TRANSMISSION THROUGH BIOCHEMICAL NETWORKS IN RESPONSE TO THE PULSED STIMULI

Two important regulatory pathways of NF-κB and MAPK were found to transmit merely one bit of information about the level of constant stimulation with, respectively, TNF and EGF [1, 2]. This somewhat surprising result may suggest that these pathways evolved to process analog inputs into physiologically interpretable binary outputs. In the case of NFκB, at small TNF doses, information is restricted by intrinsic noise, whereas at large TNF doses, by saturability of pathway components [3]. The MAPK signaling system combines a fast positive feedback with a slow negative feedback, and exhibits relaxation oscillations or pulsed responses of predefined amplitude [4]. Although being capable of transmitting a single bit about the stimulation dose, both NF-κB and MAPK pathways can respond in a pulsatory manner to the repeated pulses of the stimuli.
Lilly, Vir Biotechnology and GSK announce first patient dosed in expanded BLAZE-4 trial evaluating bamlanivimab (LY-CoV555) with VIR-7831 (GSK4182136) for COVID-19

INDIANAPOLIS and SAN FRANCISCO and LONDON, Jan. 27, 2021 /PRNewswire/ -Eli Lilly and Company (NYSE: LLY), Vir Biotechnology, Inc. (NASDAQ: VIR) and GlaxoSmithKline plc (LSE/NYSE: GSK) today announced a collaboration to evaluate a combination of two COVID-19 therapies in low-risk patients with mild to moderate COVID-19. Lilly has expanded its ongoing BLAZE-4 trial to evaluate the administration of bamlanivimab (LY-CoV555) 700mg with VIR-7831 (also known as GSK4182136) 500mg, two neutralizing antibodies that bind to different epitopes of the SARS-CoV-2 spike protein. This unique collaboration marks the first time that monoclonal antibodies from separate companies will be brought together to explore potential outcomes.
Chinese-to-English machine translation

The ability to automatically translate different languages from images or hand-written text has many applications in medicine, travel, education, international commerce, text digitization, and many other areas. However, the different grammar and lack of clear word boundaries in Chinese presents challenges when translating to word-based languages such as English. In this work, we have implemented a deep learning machine translation system to tackle these challenges. The deep learning algorithm takes in Chinese text as input and uses a sequence-to-sequence (seq2seq) encoder-decoder model with an attention mechanism based on Google’s Neural Machine Translation (NMT) model to translate the text to English output [8]. The model was trained using sparse categorical cross entropy loss and an Adam optimizer on paired Chinese and English text sentences from the 2019 Conference on Machine Translation, with 227,177 training pairs and 2,002 validation pairs [1]. In addition to tracking loss over training epochs, we measured the quality of our model’s translations using the BLEU score for machine translation. We compared the model’s performance to a smaller baseline model with no pre-trained embed-dings, as well as several less complex models with different learning rates. Our ﬁnal model achieved a maximum BLEU score of 0.247. We can further improve this score by tuning other hyperparameters and increasing the complexity of our model, as well as by training on a larger subset of the data to avoid biased results.