Miracle-dz/UniFAR-FTUs huggingface dataset:
Isothermal microcalorimetry improves accuracy and time to bacterial detection of periprosthetic joint infection after total joint arthroplasty

ABSTRACT Isothermal microcalorimetry (IMC) was evaluated compared to conventional cultures to determine the clinical performance for diagnosing periprosthetic joint infection (PJI) of hip/knee replacements. We prospectively collected three to five deep tissue samples per patient from 152 patients undergoing conversion or revision hip/knee arthroplasty from July 2020 to November 2022. Cultures and IMC for each sample were compared for concordance, median time to detection (TTD), and diagnostic performance based on 2013 Musculoskeletal Infection Society criteria. Secondary analyses involved patients on antibiotics at sampling. The 152 total patients had 592 tissue samples (mean 3.9 ± 0.3) with sample concordance between cultures and IMC of 90%. IMC demonstrated a sensitivity of 83%, specificity of 100%, negative predictive value (NPV) of 89%, and positive predictive value (PPV) of 100% for PJI. Cultures resulted in 69% sensitivity, 100% specificity, 81% NPV, and 100% PPV. The accuracy of IMC was 93% compared to 87% for cultures (P < 0.001). The median TTD of PJI by cultures was 51 (21–410) hours compared to 10 (0.5–148) hours for IMC (P < 0.001). For 39 patients on chronic antibiotics, sensitivity in PJI detection was 93%, specificity 100%, NPV 85%, and PPV 100% by IMC compared to 79% sensitivity, 100% specificity, 65% NPV, and 100% PPV for cultures. The accuracy was 95% for IMC compared to 85% for cultures (P < 0.001) with median TTD of 12 (0.5–127) hours compared to 52 (21–174) hours (P < 0.001). Utilizing IMC for PJI detection improves TTD by nearly 2 days while improving diagnostic accuracy compared to cultures, particularly in patients on chronic antibiotics.
MACE and VTE across upadacitinib clinical trial programmes in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis

Objectives To provide an integrated analysis of major adverse cardiovascular events (MACEs) and events of venous thromboembolism (VTE) and associated risk factors across rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) phase 2b/3 upadacitinib clinical programmes. Methods Data were analysed and summarised from clinical trials of RA, PsA and AS treated with upadacitinib 15 mg once daily (QD) and 30 mg QD (as of 30 June 2021). Data from adalimumab (RA and PsA) and methotrexate (RA) arms were included as comparators. Adjudicated MACEs and VTE events were presented as exposure-adjusted rates per 100 patient-years (E/100 PY). Univariable Cox proportional hazard regression analyses assessed potential associations of risk factors for MACE and VTE. Results In total, 4298 patients received upadacitinib 15 mg (RA n=3209, PsA n=907 and AS n=182) and 2125 patients received upadacitinib 30 mg (RA n=1204 and PsA n=921). In patients with RA and PsA, rates of MACE (0.3–0.6 E/100 PY) and VTE (0.2–0.4 E/100 PY) were similar across upadacitinib doses; in patients with AS, no MACEs and one VTE event occurred. Most patients experiencing MACEs or VTE events had two or more baseline cardiovascular risk factors. Across RA and PsA groups, rates of MACEs and VTE events were similar. Conclusions Rates of MACEs and VTE events with upadacitinib were consistent with previously reported data for patients receiving conventional synthetic and biologic disease-modifying anti-rheumatic drugs and comparable with active comparators adalimumab and methotrexate. Associated patient characteristics are known risk factors for MACEs and VTE events. Trial registration numbers RA (SELECT-NEXT: NCT02675426; SELECT-MONOTHERAPY: NCT02706951; SELECT-BEYOND: NCT02706847; SELECT-COMPARE: NCT02629159; SELECT-EARLY: NCT02706873, SELECT-CHOICE: NCT03086343), PsA (SELECT-PsA 2: NCT03104374; SELECT-PsA 1: NCT03104400), and AS (SELECT-AXIS 1: NCT03178487).
Socio-demographic, migratory and health-related determinants of food insecurity among Venezuelan migrants in Peru

Abstract Objective: To evaluate the factors associated with food insecurity (FI) among Venezuelan migrants residing in Peru. Secondarily, to evaluate the psychometric properties of the Food Insecurity Experience Scale (FIES). Design: A cross-sectional study based on secondary data analysis of the 2022 Venezuelan Population Residing in Peru Survey (ENPOVE-2022, from the Spanish acronym) was conducted. FI was measured with the FIES, whose properties were tested using the Rasch model. Multinomial logistic regression was performed to estimate relative prevalence ratios with their corresponding 95 % confidence intervals. Setting: This survey was conducted in February and March 2022 in the eight cities most populated by Venezuelan migrants and refugees in Peru. Participants: Venezuelan migrants and refugees over the age of 18 years living in Peru. Results: A total of 7727 participants were included. Rasch reliability was adequate (0·73). The prevalence of mild, moderate and severe FI was 36·71 %, 31·14 % and 10·48 %, respectively. Being aged 25–34 and 35–44 years, unemployed, uninsured, having no formal education or secondary, illegal status, living in a dwelling with 2–4 and more than 4 people, presenting one or more than one chronic disease, residing in Peru for 0–6 months and perceived discrimination were associated with a higher probability of moderate FI. Furthermore, having secondary education, being unemployed, uninsured, never married, illegal, residing in Tumbes, presenting one or more than one chronic disease and perceived discrimination were significantly associated with severe FI. Conclusion: Four out of ten Venezuelan migrants residing in Peru presented moderate to severe FI. The FIES showed adequate psychometric properties. Differences in the socio-demographic, health and migratory factors associated with FI levels were found. Inter-sectoral and multi-sectoral interventions are needed and should be focused on addressing the determinants of FI.
The tumor immune microenvironment in pancreatic cancer and its potential in the identification of immunotherapy biomarkers

ABSTRACT Introduction Pancreatic cancer (PC) has an extremely poor prognosis, even with surgical resection and triplet chemotherapy treatment. Cancer immunotherapy has been recently approved for tumor-agnostic treatment with genome analysis, including in PC. However, it has limited efficacy. Areas covered In addition to the low tumor mutation burden, one of the difficulties of immunotherapy in PC is the presence of abundant stromal cells in its microenvironment. Among stromal cells, cancer-associated fibroblasts (CAFs) play a major role in immunotherapy resistance, and CAF-targeted therapies are currently under development, including those in combination with immunotherapies. Meanwhile, microbiomes and tumor-derived exosomes (TDEs) have been shown to alter the behavior of distant receptor cells in PC. This review discusses the role of CAFs, microbiomes, and TDEs in PC tumor immunity. Expert opinion Elucidating the mechanisms by which CAFs, microbiomes, and TDEs are involved in the tumorigenesis of PC will be helpful for developing novel immunotherapeutic strategies and identifying companion biomarkers for immunotherapy. Spatial single-cell analysis of the tumor microenvironment will be useful for identifying biomarkers of PC immunity. Furthermore, given the complexity of immune mechanisms, artificial intelligence models will be beneficial for predicting the efficacy of immunotherapy.
Chapter 6 The rock coast of continental Europe in the Atlantic

Abstract Rocky coasts occur along more than one-third (37%) of the Atlantic continental European coastline, approximately 3666 km, often forming vertical cliffs and characteristically gently sloping shore platforms. The continental European Atlantic rocky coasts show a great variability of rock types and structural contexts, as well as different wave climates and tidal ranges. Through a review of previously published data on cliff retreat rates and shore platform erosion measured on monthly, seasonal, annual and decadal timescales, this paper highlights the different processes and agents, their magnitude and frequency in shaping rocky coasts. In particular, the links between cliff retreat, shore platform evolution, present dynamics and inheritance (understood as whether platform and other rock coast features were shaped by a higher sea level than the present) comprise one of the major contributions from continental European Atlantic rocky coasts to a global understanding of rock coast coastal geomorphology.
Inhibition of smooth muscle cell death by Angiotensin 1-7 protects against abdominal aortic aneurysm

Abstract Abdominal aortic aneurysm (AAA) represents a debilitating vascular disease characterized by aortic dilatation and wall rupture if it remains untreated. We aimed to determine the effects of Ang 1-7 in a murine model of AAA and to investigate the molecular mechanisms involved. Eight- to 10-week-old apolipoprotein E-deficient mice (ApoEKO) were infused with Ang II (1.44 mg/kg/day, s.c.) and treated with Ang 1-7 (0.576 mg/kg/day, i.p.). Echocardiographic and histological analyses showed abdominal aortic dilatation and extracellular matrix remodeling in Ang II-infused mice. Treatment with Ang 1-7 led to suppression of Ang II-induced aortic dilatation in the abdominal aorta. The immunofluorescence imaging exhibited reduced smooth muscle cell (SMC) density in the abdominal aorta. The abdominal aortic SMCs from ApoEKO mice exhibited markedly increased apoptosis in response to Ang II. Ang 1-7 attenuated cell death, as evident by increased SMC density in the aorta and reduced annexin V/propidium iodide-positive cells in flow cytometric analysis. Gene expression analysis for contractile and synthetic phenotypes of abdominal SMCs showed preservation of contractile phenotype by Ang 1-7 treatment. Molecular analyses identified increased mitochondrial fission, elevated cellular and mitochondrial reactive oxygen species (ROS) levels, and apoptosis-associated proteins, including cytochrome c, in Ang II-treated aortic SMCs. Ang 1-7 mitigated Ang II-induced mitochondrial fission, ROS generation, and levels of pro-apoptotic proteins, resulting in decreased cell death of aortic SMCs. These results highlight a critical vasculo-protective role of Ang 1-7 in a degenerative aortic disease; increased Ang 1-7 activity may provide a promising therapeutic strategy against the progression of AAA.
Gut microbiota and tumor-associated macrophages: potential in tumor diagnosis and treatment

ABSTRACT Avoiding immune destruction and polymorphic microbiomes are two key hallmarks of cancer. The tumor microenvironment (TME) is essential for the development of solid tumors, and the function of tumor-associated macrophages (TAMs) in the TME is closely linked to tumor prognosis. Therefore, research on TAMs could improve the progression and control of certain tumor patients. Additionally, the intestinal flora plays a crucial role in metabolizing substances and maintaining a symbiotic relationship with the host through a complex network of interactions. Recent experimental and clinical studies have suggested a potential link between gut microbiome and TME, particularly in regulating TAMs. Understanding this association could improve the efficacy of tumor immunotherapy. This review highlights the regulatory role of intestinal flora on TAMs, with a focus on gut microbiota and their metabolites. The implications of this association for tumor diagnosis and treatment are also discussed, providing a promising avenue for future clinical treatment strategies.
Percolation Theory: A Model For Rock Fracture?

SUMMARY Recent theoretical advances have confirmed the status of the so-called ‘scaling relations’ for percolation theory. On this pretext, their implications for the treatment of rock fracture are re-examined. Comparison between predicted and observed b-values suggest that classical percolation may be a less appropriate model than had been anticipated. Directed variants, such as first-passage, oriented and invasion percolation, may prove more successful, but at present little firm theoretical knowledge exists concerning their cluster properties. At the present time the simpler branching process appears to offer as effective a model as any for rock fracture. Major ambiguities of interpretation prevent any clear conclusions from being drawn.
Evaluating the effect of conditioned medium from mesenchymal stem cells on differentiation of rat spermatogonial stem cells

In cancer patients, chemo/radio therapy may cause infertility by damaging the spermatogenesis affecting the self-renewal and differentiation of spermatogonial stem cells (SSCs). In vitro differentiation of stem cells especially mesenchymal stem cells (MSCs) into germ cells has recently been proposed as a new strategy for infertility treatment. The aim of this study was to evaluate the proliferation and differentiation of SSCs using their co-culture with Sertoli cells and conditioned medium (CM) from adipose tissue-derived MSCs (AD-MSCs). Testicular tissues were separated from 2–7 days old neonate Wistar Rats and after mechanical and enzymatic digestion, the SSCs and Sertoli cells were isolated and cultured in Dulbecco’s modified eagle medium with 10% fetal bovine serum, 1X antibiotic, basic fibroblast growth factor, and glial cell line-derived neurotrophic factor. The cells were treated with the CM from AD-MSCs for 12 days and then the expression level of differentiation-related genes were measured. Also, the expression level of two major spermatogenic markers of DAZL and DDX4 was calculated. Scp3, Dazl, and Prm1 were significantly increased after treatment compared to the control group, whereas no significant difference was observed in Stra8 expression. The immunocytochemistry images showed that DAZL and DDX4 were positive in experimental group comparing with control. Also, western blotting revealed that both DAZL and DDX4 had higher expression in the treated group than the control group, however, no significant difference was observed. In this study, we concluded that the CM obtained from AD-MSCs can be considered as a suitable biological material to induce the differentiation in SSCs.
Validating Earth and ocean tide models using tidal gravity measurements

SUMMARY O1 and M2 observations from well-calibrated spring gravimeters and superconducting gravimeters from the Global Geodynamics Project (GGP) are used to test models of the Earth’s body tide and 10 ocean tide models. It is shown that some of the ocean tide models give anomalous results in various parts of the world. For example, the Schwiderski ocean tide model gives discrepancies in several areas and the FES series of ocean tide models have problems in the western Pacific (China, Japan and Australia). The majority of the high-quality tidal gravity measurements in Europe are in close agreement with the Dehant, Defraigne and Wahr (DDW) elastic and inelastic body tide models. The gravimetric factors for the DDW elastic and inelastic models only differ by 0.12 per cent and the present calibration accuracy does not allow us to distinguish between these models, but does reduce the previous upper bound on inelastic gravimetric factors. The European observations give a phase lag of a few hundredths of a degree for the O1 body gravity tide, which is consistent with the Mathews inelastic body tide model. At some European and worldwide stations the gravimetric factors differ by up to 0.3 per cent from the DDW model and it is suggested that further checks on the gravimeter calibrations are required. Accurate determinations of instrumental phase lags are now easier to achieve and the imaginary (out-of-phase) component of tidal gravity can be used for accurate tests of this component of ocean tide models.
Enhanced soil moisture drying in transitional regions under a warming climate

We analyzed global trends of soil moisture for the period 1948–2010 using the Global Land Data Assimilation System data set. Soil moisture was dominated by negative trends, with pronounced drying over East Asia and the Sahel. Spatial analysis according to climatic region revealed that the most obvious drying occurred over transitional regions between dry and wet climates. The noticeable drying first took place in the humid transitional regions and extended to the dry transitional regions, beginning in the 1980s. The variability of soil moisture was notably related to the changes in precipitation and temperature, but with different roles. For the global average, precipitation had a dominant effect on the variability of soil moisture at interannual to decadal time scales, but temperature was the main cause of the long‐term trend of soil moisture on the whole. The enhanced soil drying in the transitional regions was primarily caused by global warming, which is illustrated by regression analysis and the land surface model.
External and Internal Validity Considerations in Youth Effectiveness Trials: Lessons Learned from the COMET Study

ABSTRACT Objective Effectiveness trials aim to increase the generalizability and public health impact of interventions. However, challenges associated with this design present threats to external and internal validity. This paper illustrates these challenges using data from a two-site randomized effectiveness trial, the Community Study of Outcome Monitoring for Emotional Disorders in Teens (COMET) and presents recommendations for future research. Method COMET was a randomized effectiveness trial conducted in 19 community mental health clinics in two states comparing three interventions: treatment as usual (TAU), TAU with measurement-based care (TAU+), and the Unified Protocol forTransdiagnostic Treatment of Emotional Disorders in Adolescents with MBC (UPA). Participants included 176 clinicians (mean age = 35.5; 85.8% cisgender female; 53.0% racially and/or ethnically minorized) and 196 adolescents (mean age = 14.7; 65.3% cisgender female; 69.4% racially and/or ethnically minorized). Analyses outlined participant flow from recruitment to study completion, described participant characteristics, and examined site differences. Results Analysis of participant flow suggested that recruitment and retention of clinicians and adolescents was challenging, raising questions about whether participants were representative of participating clinics. Both the clinician and adolescent samples were racially and ethnically diverse and adolescents were low income and clinically complex. Significant site differences were observed in clinician and adolescent characteristics. Conclusions While this study was successful in recruiting a diverse and historically under-represented sample, difficulties in recruitment and retention raise questions about external validity and site differences present challenges to internal validity of study findings. Suggestions for future effectiveness studies, drawing from implementation science approaches, are discussed.
An updated patent review of GPR40/ FFAR1 modulators (2020 – present)

ABSTRACT Introduction Free fatty acid receptor 1 (FFAR1) is a potential therapeutic target for type 2 diabetes mellitus (T2DM) because it could clinically stimulate insulin release in a glucose-dependent manner without inducing hypoglycemia. In both the pharmaceutical industry and academic community, FFAR1 agonists have attracted considerable attention. Areas covered The review presents a patent overview of FFAR1 modulators in 2020–2023, along with chemical structures, the biological activities and therapeutic applications of the representative compounds. Our patent survey used the major electronic databases, namely SciFinder, and Web of Science and Innojoy. Expert opinion Although FFAR1 agonists exhibit outstanding advantages, they are also associated with significant challenges. At present, reducing the molecular weight and overall lipophilicity and developing tissue-specific FFAR1 agonists may be the strategies for alleviating hepatotoxicity.
India: skilled migration to developed countries, labour migration to the gulf

st –century exodus of the IT workers. Beginning with the oil–boom of the 1970s, large numbers of unskilled and semi–skilled Indian labour have migrated to Gulf countries in west Asia. A paradigm shift about skilled migrants leaving India took place in phases – from the «brain drain» of 1960s – 1970s to «brain bank» of 1980s – 1990s, and subsequently to «brain gain» in the 21 st century. Similarly, the labour migrants to the Gulf have been viewed as the main source of remittances, swelling India’s foreign exchange reserves. Both these perceptions need moderation. Section 2 presents a general contextual background of India. Sections 3 and 4 highlight India’s transnational connectivity through skilled migrants in the developed coun � tries, in particular the US. Section 5 is on labour migration to the Gulf. Section 6 is on the socio– economic impacts of Gulf migration on Kerala, an important Indian state of origin. Section 7 is on the evolution and change in the perception of migration in India. Section 8 analyses mea � sures initiated by the Government of India recently. The concluding section is a commentary on whether and how migration could change society in India and the rest of the South.
Antibodies against the Mycobacterium tuberculosis complex and Brucella spp. in captive and free‐living European bison (Bison bonasus) in Poland

Abstract Background The European bison (Bison bonasus), a symbol of Polish nature, is a protected species that requires active health monitoring. However, conservation efforts are made difficult by the zoonotic diseases such as brucellosis and tuberculosis. Objective The aim of this study was to screen the Polish European bison population for exposure to the Mycobacterium tuberculosis complex (MTC) and Brucella spp. Methods A total of 323 free‐living and captive European bison from 13 localities were tested serologically for antibodies against the M. bovis P22 multi‐protein complex (in‐house ELISA) and against Brucella spp. (commercial ELISA). Results Antibodies against the MTC (P22) were detected in 7% (22/323) of the tested European bison. Anti‐MTC antibody positivity was not significantly different by sex, age, and captive/free range status. Anti‐MTC antibodies were found in six of 13 populations sampled, always in populations with larger sample sizes including the four free‐living ones. Antibodies against Brucella spp. were detected in 36% (116/323) of the tested bison. While Brucella spp. antibody prevalence was not different by sex, it was significantly different by age (lower in adults) and captive/free‐living status. Brucella spp. seroprevalence decreased with sample size and seropositive bison were found in 12 of 13 sampling populations. Conclusions Our findings identify potential emerging threats to the European bison population and confirm the first serological response to P22 in European bison. As Poland is currently officially free of brucellosis and bovine tuberculosis, our results require careful interpretation. Further studies are needed to establish the presence of cross‐reactions with atypical mycobacteria in the case of MTC and other bacteria (e.g. Yersinia enterocolitica O:9) in the case of Brucella spp.