Miracle-dz/UniFAR-FTUs huggingface dataset:
Risk of cervical precancer among HPV–negative women in the Netherlands and its association with previous HPV and cytology results: A follow-up analysis of a randomized screening study

Background Human papillomavirus (HPV)-based screening programs still use one-size-fits-all protocols but efficiency and efficacy of programs may be improved by stratifying women based on previous screening results. Methods and findings We studied the association between cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) and previous screening results in the Population-Based Screening Study Amsterdam (POBASCAM) trial, performed in the Netherlands in the setting of regular screening, where women aged from 29 to 61 years old were invited to cytology and HPV co-testing at enrolment in year 1999/2002 and at the next round in 2003/2007. We selected 18,448 women (9,293 from the intervention group and 9,155 from the control group) who tested HPV–negative in 2003/2007 and did not have cervical intraepithelial neoplasia grade 2 or worse (CIN2+) or hysterectomy after enrolment. Follow-up was collected until 14 years after the 2003/2007 screen, covering 4 rounds of screening. Risk of CIN3+ and CIN2+ among women with an HPV–negative test, irrespective of previous round results and stratified according to previous round HPV and cytology results, were calculated by the Kaplan–Meier method. During 14 years of follow-up, 62 CIN3+ cases (24 in the intervention group and 38 in the control group) were detected. HPV–negative women had a 14-year CIN3+ risk of 0.48% (95% confidence interval 0.37 to 0.62) and CIN2+ risk of 1.17% (0.99 to 1.38). The CIN3+ risk among HPV–negative women was increased in women with a previous positive HPV test (2.36%, 1.20 to 4.63; p < 0.001) or co-test (1.68%, 0.87 to 3.20; p < 0.001) and, equivalently, decreased in women with a previous negative HPV test (0.43%, 0.33 to 0.57) or a negative co-test (0.43%, 0.33 to 0.57). The CIN3+ risk was not influenced by the previous cytology result. The CIN3+ risk among HPV–negative women was increased after both a previous HPV16–positive test (3.90%, 1.47 to 10.12; p < 0.001) and a previous HPV16–negative/HPVother–positive test (1.91%, 0.76 to 4.74; p = 0.002). For endpoint CIN2+ (147 cases), findings were similar except that the CIN2+ risk was increased after previous abnormal cytology (4.06%, 2.30 to 7.12; p < 0.001). The presented risk estimates were calculated by tracking histological results through the Dutch nationwide pathology archive (PALGA) and were not adjusted for non-compliance with the colposcopy referral advice. Conclusions HPV–negative women had an increased long-term risk of CIN3+ when the HPV test in the previous screening round was positive. This supports the implementation of risk-based intervals that depend on HPV results in the current and previous screening round. Trial registration POBASCAM trial, trial registration number ISRCTN20781131.
Biomechanical Analysis of Posterior Open-Wedge Osteotomy and Glenoid Concavity Reconstruction Using an Implant-Free, J-Shaped Iliac Crest Bone Graft

Background: Posterior open-wedge osteotomy and glenoid reconstruction using a J-shaped iliac crest bone graft showed promising clinical results for the treatment of posterior instability with excessive glenoid retroversion and posteroinferior glenoid deficiency. Purpose: To evaluate the biomechanical performance of the posterior J-shaped graft to restore glenoid retroversion and posteroinferior deficiency in a cadaveric shoulder instability model. Study Design: Controlled laboratory study. Methods: A posterior glenoid open-wedge osteotomy was performed in 6 fresh-frozen shoulders, allowing the glenoid retroversion to be set at 0°, 10°, and 20°. At each of these 3 preset angles of glenoid retroversion, the following conditions were simulated: (1) intact joint, (2) posterior Bankart lesion, (3) 20% posteroinferior glenoid deficiency, and (4) posterior J-shaped graft (at 0° of retroversion). With the humerus in the Jerk position (60° of glenohumeral anteflexion, 60° of internal rotation), stability was evaluated by measuring posterior humeral head (HH) translation (in mm) and peak translational force (in N) to translate the HH over 25% of the glenoid width. Glenohumeral contact patterns were measured using pressure-sensitive sensors. Fixation of the posterior J-graft was analyzed by recording graft micromovements during 3000 cycles of 5-mm anteroposterior HH translations. Results: Reconstructing the glenoid with a posterior J-graft to 0° of retroversion significantly increased stability compared with a posterior Bankart lesion and posteroinferior glenoid deficiency in all 3 preset degrees of retroversion (P < .05). There was no significant difference in joint stability comparing the posterior J-graft with an intact joint at 0° of retroversion. The posterior J-graft restored mean contact area and contact pressure comparable with that of the intact condition with 0° of retroversion (222 vs 223 mm2, P = .980; and 0.450 vs 0.550 MPa, P = .203). The mean total graft displacement after 3000 cycles of loading was 43 ± 84 µm, and the mean maximal mediolateral graft bending was 508 ± 488 µm. Conclusion: Biomechanical analysis of the posterior J-graft demonstrated reliable restoration of initial glenohumeral joint stability, normalization of contact patterns comparable with that of an intact shoulder joint with neutral retroversion, and secure initial graft fixation in the cadaveric model. Clinical Relevance: This study confirms that the posterior J-graft can restore stability and glenohumeral loading conditions comparable with those of an intact shoulder.
Discovery of a Novel Potent Antitumor Molecule, P19G1, by Erlotinib Derivative Libraries Synthesized by Modular Click-Chemistry

Objective:Traditional chemical synthesis methods are cumbersome and inefficient. In this study, a novel antitumor molecule, 4-(4-(3-((6,7-bis(2-methoxyethoxy)quinazolin-4-yl)amino)phenyl)-1H-1,2,3-triazol-1-yl)phenyl sulfurofluoridate (P19G1), was identified by screening a library of Erlotinib derivatives synthesized by modular click chemistry, and the antitumor activity and underlying mechanism of P19G1 were further revealed. Methods: A series of Erlotinib derivatives (840 compounds) were synthesized using a modular click-chemistry method, and then the thiazolyl blue (MTT) method was used to screen and evaluate the inhibitory effect of these compounds on the growth and metastasis of A549 lung adenocarcinoma cells. Among them, the compound P19G1 showed the best inhibitory activity. Furthermore, the antitumor activity and mechanism of P19G1 were investigated with in vitro cell biology and in vivo assays in an animal model. Results: In vitro pharmacological studies showed that P19G1 had inhibitory effects on a variety of tumor cell lines with IC50 values in the range of 1 to 5 μM. Moreover, P19G1 significantly inhibited the proliferation and migration of the human lung adenocarcinoma cell line A549 and human colorectal cancer cell line RKO and promoted cell apoptosis. In vivo tumor-bearing mouse model experiments revealed that 50 mg/kg P19G1 effectively inhibited the growth and metastasis of A549 tumors without obvious toxicity to the host. Conclusions: The rapid structural modification of lead compounds using novel modular click-chemistry reactions holds great potential for use in obtaining diverse derivatives for tumor drug screening and development. P19G1 was discovered because of the application of click chemistry in this study, and it is an antitumor candidate molecule worthy of development.
A small molecule M1 promotes optic nerve regeneration to restore target-specific neural activity and visual function

Significance Retinal ganglion cells typically fail to regenerate injured axons after injury, leading to permanent visual loss after optic nerve damage. Activation of intrinsic growth capacity, an energy-demanding process, facilitates axonal regrowth from injured neurons. Here, we demonstrate that M1, a small molecule that promotes mitochondrial fusion and motility, enhances intrinsic growth capacity of injured neurons and accelerates in vivo axon regeneration of injured neurons. More strikingly, M1 treatment sustains long-distance axon regeneration from optic chiasm to multiple subcortical visual targets in the brain. Regenerated axons elicit neural activities in target brain regions and restore pupillary light reflex and responses to looming visual stimuli. Our study highlights the potential of nonviral, mitochondria-based therapy for nervous system repair.
Therapeutic role of nitroglycerin against copper-nitrilotriacetate induced hepatic and renal damage

Earlier we have shown that exposure to copper-nitrilotriacetate (Cu-NTA) manifests toxicity by generating oxidative stress and potent induction of proliferative reaction in the liver and kidney. In the study, we look at the impact of nitroglycerin (GTN) administration on Cu-NTA-induced oxidative stress and hyperproliferative response in the liver and kidney. GTN administration intraperitoneally to male Wistar rats after Cu-NTA administration intraperitoneally caused substantial protection against Cu-NTA-induced tissue injury, oxidative stress and hyperproliferative response. Cu-NTA administration at a dose of 4.5 mg/kg body weight produces significant (p < .001) elevation in biochemical parameters including aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN) and creatinine (CREA) with a concomitant increase in microsomal lipid peroxidation. Along with these alterations, we discovered a substantial increment in [3H]thymidine incorporation into hepatic and renal DNA synthesis (p < .001). Cu-NTA-induced tissue damage and lipid peroxidation in hepatic and renal tissues were inhibited by GTN treatment in a dose-dependent manner (p < .05–0.001). Furthermore, GTN can suppress the hyperproliferative response elicited by Cu-NTA by down-regulating the rate of [3H]thymidine incorporation into hepatic and renal DNA (p < .01–0.001). Protective effect of GTN against Cu-NTA was also confirmed by histopathological changes in liver and kidney. This result suggests that GTN may serve as a scavenger for reactive oxygen species (ROS) and reduces toxic metabolites of Cu-NTA, thereby avoiding tissue injury and oxidative stress. Further, administration of NO inhibitor, NG-Nitroarginine methyl ester (L-NAME), exacerbated Cu-NTA induced oxidative tissue damage and cell proliferation. Overall, GTN reduces Cu-NTA-induced tissue damage, oxidative stress, and proliferative response in the rat liver and kidney, according to these findings. On the basis of the above results, present study suggests that GTN may be a potential therapeutic agent for restoration of oxidative damage and proliferation to liver and kidney.
Surface waves and crustal structure on Mars

We detected surface waves from two meteorite impacts on Mars. By measuring group velocity dispersion along the impact-lander path, we obtained a direct constraint on crustal structure away from the InSight lander. The crust north of the equatorial dichotomy had a shear wave velocity of approximately 3.2 kilometers per second in the 5- to 30-kilometer depth range, with little depth variation. This implies a higher crustal density than inferred beneath the lander, suggesting either compositional differences or reduced porosity in the volcanic areas traversed by the surface waves. The lower velocities and the crustal layering observed beneath the landing site down to a 10-kilometer depth are not a global feature. Structural variations revealed by surface waves hold implications for models of the formation and thickness of the martian crust. Description An insightful impact On 24 December 2021, the seismometer for the InSight mission on Mars detected a large seismic event with a distinct signature. Posiolova et al. discovered that the event was caused by a meteor impact on the surface of Mars, which was confirmed by satellite observations of a newly formed 150-kilometer crater. The surface nature and size of the impact allowed Kim et al. to detect surface waves from the event, which have yet to be observed on Mars. These surface waves help to untangle the structure of the Martian crust, which has various amounts of volcanic and sedimentary rock, along with subsurface ice, in different regions of the planet (see the Perspective by Yang and Chen). The characteristics of the impact itself are important because they provide a seismic fingerprint of an impact event that is different from the marsquakes observed so far. —BG A new crater formed on the surface of Mars was detected with the seismometer on the InSight mission.
The dynamics of integration and integrated care: An exploratory study of physician organizations

Background Substantial variation exists in how well health care is integrated, even across similarly structured organizations, yet research about what physician organizations (POs) do that enables or inhibits integrated care is limited. Purpose The aim of this study was to explore the dynamics that enable POs to integrate care. Methodology/Approach We ranked a stratified sample of POs according to patient perceptions of integrated care, as measured in a survey. We interviewed professionals, patients, and family members in 10 higher and 3 lower ranked POs about the process of caring for patients with complex conditions. We derived integration-related themes from the interview data and quantified their prevalence. Using a quasi-statistical approach, we explored relationships among themes and their associations with patient perceptions of integrated care. Results From 6,104 coded references, we derived a set of themes representing integration perspectives, integration engagement mechanisms, and integration failures. POs experienced frequent integration failures. Higher ranked POs experienced these failures less often because of a combination of functional, interpersonal, and stakeholder engagement mechanisms, which appear to complement one another. Integration perspectives, including both people-oriented and systems-oriented mindsets, appear to play a role in generating these integration dynamics. Conclusion Delivering integrated care depends on a PO’s ability to limit integration failures, keeping provider attention focused on patients. Building on the attention-based view, we present a framework suggesting that this ability is a function of both integration perspectives and integration engagement mechanisms. Practice Implications POs interested in delivering more integrated care should employ a variety of complementary integration engagement mechanisms and facilitate these efforts by nurturing both people-oriented and system-oriented mindsets among PO decision-makers.
Zero-Sum Differential Game-Based Fault-Tolerant Control for a Class of Affine Nonlinear Systems

This article proposes a zero-sum differential game-based control scheme for a class of affine nonlinear control systems with actuator faults, including loss of control, loss of effectiveness, and bias faults. In the control design, the bias faults and the control signal are chosen as the two opposite sides. The Nash equilibrium is achieved while the optimal control signal and the upper bound of bias faults can be derived from the Hamilton–Jacobi–Isaacs (HJI) equation. An adaptive dynamic programming (ADP) method is employed to estimate the weight of the critic network. The developed zero-sum differential game-based control scheme can ensure the system stability and optimal performance. Two simulation results on a numerical system and a rigid spacecraft model illustrate the effectiveness of the proposed control scheme.
Peripheral Blood Monocyte Abundance Predicts Outcomes in Patients with Breast Cancer

Biomarkers of response are needed in breast cancer to stratify patients to appropriate therapies and avoid unnecessary toxicity. We used peripheral blood gene expression and cell-type abundance to identify biomarkers of response and recurrence in neoadjuvant chemotherapy–treated patients with breast cancer. We identified a signature of IFN and complement response that was higher in the blood of patients with pathologic complete response. This signature was preferentially expressed by monocytes in single-cell RNA sequencing. Monocytes are routinely measured clinically, enabling examination of clinically measured monocytes in multiple independent cohorts. We found that peripheral monocytes were higher in patients with good outcomes in four cohorts of patients with breast cancer. Blood gene expression and cell type abundance biomarkers may be useful for prognostication in breast cancer. Significance: Biomarkers are needed in breast cancer to identify patients at risk for recurrence. Blood is an attractive site for biomarker identification due to the relative ease of longitudinal sampling. Our study suggests that blood-based gene expression and cell-type abundance biomarkers may have clinical utility in breast cancer.
An updated Type II supernova Hubble diagram

We present photometry and spectroscopy of nine Type II-P/L supernovae (SNe) with redshifts in the 0.045 < z < 0.335 range, with a view to re-examining their utility as distance indicators. Specifically, we apply the expanding photosphere method (EPM) and the standardized candle method (SCM) to each target, and find that both methods yield distances that are in reasonable agreement with each other. The current record-holder for the highest-redshift spectroscopically confirmed SN II-P is PS1-13bni (z = 0.335 +0.009 -0.012), and illustrates the promise of Type II SNe as cosmological tools. We updated existing EPM and SCM Hubble diagrams by adding our sample to those previously published. Within the context of Type II SN distance measuring techniques, we investigated two related questions. First, we explored the possibility of utilising spectral lines other than the traditionally used Fe II 5169 to infer the photospheric velocity of SN ejecta. Using local well-observed objects, we derive an epoch-dependent relation between the strong Balmer line and Fe II 5169 velocities that is applicable 30 to 40 days post-explosion. Motivated in part by the continuum of key observables such as rise time and decline rates exhibited from II-P to II-L SNe, we assessed the possibility of using Hubble-flow Type II-L SNe as distance indicators. These yield similar distances as the Type II-P SNe. Although these initial results are encouraging, a significantly larger sample of SNe II-L would be required to draw definitive conclusions.
A semi-relativistic treatment of spinless particles subject to the nuclear Woods-Saxon potential

By applying an appropriate Pekeris approximation to deal with the centrifugal term, we present an approximate systematic solution of the two-body spinless Salpeter (SS) equation with the Woods-Saxon interaction potential for an arbitrary l-state. The analytical semi-relativistic bound-state energy eigenvalues and the corresponding wave functions are calculated. Two special cases from our solution are studied: the approximated Schrödinger-Woods-Saxon problem for an arbitrary l-state and the exact s-wave (l=0).
Common data model for COVID-19 datasets

Abstract Motivation A global medical crisis like the coronavirus disease 2019 (COVID-19) pandemic requires interdisciplinary and highly collaborative research from all over the world. One of the key challenges for collaborative research is a lack of interoperability among various heterogeneous data sources. Interoperability, standardization and mapping of datasets are necessary for data analysis and applications in advanced algorithms such as developing personalized risk prediction modeling. Results To ensure the interoperability and compatibility among COVID-19 datasets, we present here a common data model (CDM) which has been built from 11 different COVID-19 datasets from various geographical locations. The current version of the CDM holds 4639 data variables related to COVID-19 such as basic patient information (age, biological sex and diagnosis) as well as disease-specific data variables, for example, Anosmia and Dyspnea. Each of the data variables in the data model is associated with specific data types, variable mappings, value ranges, data units and data encodings that could be used for standardizing any dataset. Moreover, the compatibility with established data standards like OMOP and FHIR makes the CDM a well-designed CDM for COVID-19 data interoperability. Availability and implementation The CDM is available in a public repo here: https://github.com/Fraunhofer-SCAI-Applied-Semantics/COVID-19-Global-Model. Supplementary information Supplementary data are available at Bioinformatics online.
Community perceptions on the factors in the social food environment that influence dietary behaviour in cities of Kenya and Ghana: a Photovoice study

Abstract Objective: To explore communities’ perspectives on the factors in the social food environment that influence dietary behaviours in African cities. Design: A qualitative study using participatory photography (Photovoice). Participants took and discussed photographs representing factors in the social food environment that influence their dietary behaviours. Follow-up in-depth interviews allowed participants to tell the ‘stories’ of their photographs. Thematic analysis was conducted, using data-driven and theory-driven (based on the socio-ecological model) approaches. Setting: Three low-income areas of Nairobi (n 48) in Kenya and Accra (n 62) and Ho (n 32) in Ghana. Participants: Adolescents and adults, male and female aged ≥13 years. Results: The ‘people’ who were most commonly reported as influencers of dietary behaviours within the social food environment included family members, friends, health workers and food vendors. They mainly influenced food purchase, preparation and consumption, through (1) considerations for family members’ food preferences, (2) considerations for family members’ health and nutrition needs, (3) social support by family and friends, (4) provision of nutritional advice and modelling food behaviour by parents and health professionals, (5) food vendors’ services and social qualities. Conclusions: The family presents an opportunity for promoting healthy dietary behaviours among family members. Peer groups could be harnessed to promote healthy dietary behaviours among adolescents and youth. Empowering food vendors to provide healthier and safer food options could enhance healthier food sourcing, purchasing and consumption in African low-income urban communities.
A systematic literature review for the prediction of anticancer drug response using various machine‐learning and deep‐learning techniques

Computational methods have gained prominence in healthcare research. The accessibility of healthcare data has greatly incited academicians and researchers to develop executions that help in prognosis of cancer drug response. Among various computational methods, machine‐learning (ML) and deep‐learning (DL) methods provide the most consistent and effectual approaches to handle the serious aftermaths of the deadly disease and drug administered to the patients. Hence, this systematic literature review has reviewed researches that have investigated drug discovery and prognosis of anticancer drug response using ML and DL algorithms. Fot this purpose, PRISMA guidelines have been followed to choose research papers from Google Scholar, PubMed, and Sciencedirect websites. A total count of 105 papers that align with the context of this review were chosen. Further, the review also presents accuracy of the existing ML and DL methods in the prediction of anticancer drug response. It has been found from the review that, amidst the availability of various studies, there are certain challenges associated with each method. Thus, future researchers can consider these limitations and challenges to develop a prominent anticancer drug response prediction method, and it would be greatly beneficial to the medical professionals in administering non‐invasive treatment to the patients.