Miracle-dz/UniFAR-FTUs huggingface dataset:
A data-driven semi-parametric model of SARS-CoV-2 transmission in the United States

To support decision-making and policy for managing epidemics of emerging pathogens, we present a model for inference and scenario analysis of SARS-CoV-2 transmission in the USA. The stochastic SEIR-type model includes compartments for latent, asymptomatic, detected and undetected symptomatic individuals, and hospitalized cases, and features realistic interval distributions for presymptomatic and symptomatic periods, time varying rates of case detection, diagnosis, and mortality. The model accounts for the effects on transmission of human mobility using anonymized mobility data collected from cellular devices, and of difficult to quantify environmental and behavioral factors using a latent process. The baseline transmission rate is the product of a human mobility metric obtained from data and this fitted latent process. We fit the model to incident case and death reports for each state in the USA and Washington D.C., using likelihood Maximization by Iterated particle Filtering (MIF). Observations (daily case and death reports) are modeled as arising from a negative binomial reporting process. We estimate time-varying transmission rate, parameters of a sigmoidal time-varying fraction of hospitalized cases that result in death, extra-demographic process noise, two dispersion parameters of the observation process, and the initial sizes of the latent, asymptomatic, and symptomatic classes. In a retrospective analysis covering March–December 2020, we show how mobility and transmission strength became decoupled across two distinct phases of the pandemic. The decoupling demonstrates the need for flexible, semi-parametric approaches for modeling infectious disease dynamics in real-time.
C-reactive protein and the neutrophil-to-lymphocyte ratio on admission predicting bacteraemia with COVID-19

Abstract Background Bacteraemia can co-occur with COVID-19. The present study aimed to determine the cut-off value for C-reactive protein (CRP) and the neutrophil-to-lymphocyte ratio (NLR) for predicting bacteraemia in patients with COVID-19. Methods Patients admitted to Tokyo Metropolitan Tama Medical Centre for COVID-19 treatment between 1 April 2020 and 30 October 2022 were included. Patients transferred from other hospitals and those whose CRP and/or neutrophil count was not measured at admission were excluded. Community-acquired bacteraemia was diagnosed if true bacteraemia was diagnosed in patients via a blood culture performed within 72 h of admission. The cut-off value for CRP and the NLR for community-acquired bacteraemia were determined using receiver operating characteristic analysis. Results Among 2989 patients hospitalized for COVID-19 treatment, 19 received the diagnosis of community-acquired bacteraemia, for which CRP ≥ 6.3 was determined to be the cut-off value. The sensitivity and specificity of the cut-off was 89.5% and 73.3%, respectively. The NLR cut-off value was ≥ 7.7, which had a sensitivity and specificity of 84.2% and 84.0%, respectively. Conclusions Considering the possibility of the co-occurrence of bacteraemia with COVID-19, a blood culture should be performed when CRP is ≥ 6.3 or the NLR is ≥ 7.7.
The influence of internship training experience on Kenyan and Ugandan doctors’ career intentions and decisions: a qualitative study

ABSTRACT Background Medical internship is a key period for doctors’ individual career planning and also a transition period for the broader labour market. Objectives We aimed to understand the complex set of factors influencing the career intentions and decisions of junior doctors, post-internship in Kenya and Uganda. Methods We conducted semi-structured interviews with 54 junior medical officers and 14 consultants to understand doctors’ internship experiences and subsequent employment experiences. We analysed the data using a mix of a direct content approach, informed by an internship experience and career intentions framework developed primarily from high-income country literature, alongside a more inductive thematic analysis. Results Echoing the internship experience and career intentions framework, we found that clinical exposure during internship, work–life balance, aspects of workplace culture such as relationships with consultants and other team members, and concerns over future job security and professional development all influenced Kenyan and Ugandan doctors’ career preferences. Additionally, we added a new category to the framework to reflect our finding that interns might want to ‘fill a health system gap’ when they choose their future careers, based on what they witness as interns. However, often career intentions did not match career and employment decisions due to specific contextual factors, most importantly a shortage of job opportunities. Conclusion We have shown how internship experiences shape medical doctors’ career intentions in Kenya and Uganda and highlighted the importance of job availability and context in influencing doctors’ career choices.
Simulating Rice Response to Climate Change

The response of rice (Oryza sativa L.) to elevated CO{sub 2} concentration and temperature increase was simulated using the CERES-rice model. CERES-rice belongs to the International Benchmark Sites Network for Agrotechnology Transfer (IBSNAT) family of crop and nutrient dynamics models. Long-term historical data from the International Rice Research Institute (IRRI) wetland site was used to quantify the climatic change effects. The model simulated such beneficial effects of CO{sub 2} enrichment as increased grain yields, reduced transpiration, increased water use efficiency, improved use of intercepted radiation, reduced N losses, and higher N use efficiency. The trends were reversed for all of the above parameters with increase in temperature. CERES-rice simulated these negative trends in low input rice production as well. Based on the model`s prediction, some of the negative effects of temperature increase in warmer regions of the world could be offset by use of rice varieties that are tolerant to high temperature-induced spikelet sterility, and planting varieties with longer growth duration, particularly, longer grain filling duration. With improved varieties and good management future impact of climate change could be capitalized to have positive effects on rice production. Although the model has been extensively tested, it is critical to validate itmore » with field data from extreme temperature and CO{sub 2} level studies. 33 refs., 13 figs., 3 tabs. « less
Peripheral edema associated with antidepressant use: Systematic review of case reports

Oedema associated with psychotropics can impose a considerable burden, leading to increased morbidity and cost. Peripheral oedema is sometimes related to the use of antidepressants, which are among the most prescribed psychotropic medications. We reviewed the reported cases of antidepressant‐associated oedema to understand the risk factors, aetiology and outcome.
The Role of Shame in the Relationship between Alcohol Use Severity and Relational Intimacy among Sexual Minority Women

Abstract Background: Sexual Minority Women (SMW) are disproportionately likely to struggle with substance use and shame, two factors that are associated with poorer relationship quality and decreased relational intimacy (Doyle & Molix, 2015). However, there is a dearth of research examining shame and substance use concurrently among SMW. Objectives: The current study elucidated the role of shame-based cognitions (SBCs) and shame-based behaviors (SBBs) in explaining the relationship between alcohol use severity and relational intimacy. We recruited adult cisgender women (N = 105) in a romantic relationship who self-identified as a sexual minority and reported alcohol use during the past three months through Amazon Mechanical Turk. Participants completed an online survey assessing alcohol use, SBCs, SBBs, and relational intimacy. Results: There was a significant positive relationship between alcohol use severity with SBCs (r = .29, p = .003) and with SBBs (r = .62, p <.001). SBBs were shown to be negatively correlated with relational intimacy (r = -.48, p < .001). Parallel mediation analysis demonstrated that SBCs and SBBs accounted for approximately 34.4% of the variance in intimacy. The indirect effects of SBCs were significant (β = .10, 95% CI [.02, .18] while SBBs (β = -.14, 95% CI [-.29, .01]) did not show effects. Discussions: Given the disproportionate rates of alcohol use among SMW, this study offers a nuanced picture of the relationships between constructs known to impact alcohol use. The findings underscore the importance of SBCs and point to a potential treatment target among SMW presenting with alcohol use and diminished relational intimacy.
The value of whole-body dual-energy x-ray absorptiometry in assessing body composition in patients with inflammatory bowel disease: a prospective study

Objectives Low skeletal muscle index (SMI) is common in inflammatory bowel disease (IBD) but has an uncertain relationship with active intestinal inflammation. This study evaluated body composition by whole-body dual-energy X-ray absorptiometry (DXA) in patients with IBD and healthy controls to enable the value of formal body composition analysis to be judged. Methods Patients with IBD and sex/age-matched controls prospectively underwent full body composition assessment by DXA, assessment by BMI, eating questionnaires and handgrip strength. Disease activity was assessed by faecal calprotectin (active ≥150 µg/g). A cohort undergoing biologic induction therapy were assessed at baseline and after ≥13 weeks. Results Total fat mass was higher in 54 patients with IBD (56% Crohn’s disease, 61% male) than in 30 controls (median 25.1 vs. 18.7 kg, P = 0.042). DXA offered little more than BMI. Low SMI was more common than in controls (15% vs. 0%, P = 0.027). A normal BMI was seen in many patients with low SMI and handgrip strength was a poor marker of change in SMI. Body composition was similar in 28 patients with active vs. 22 with inactive disease. However, SMI increased specifically by 9.7% (P = 0.004) and BMI by 6.4% (P = 0.012) in 9 responders to therapy. Conclusion DXA identifies many patients with reduced SMI who are not detected by standard methodologies. While disease activity is not associated with low SMI, resolution of inflammation leads to improved SMI. The potential for recognition of such patients to influence therapeutic decisions underlines the need for DXA assessment in clinical practice.
Mechanisms of carboplatin‐ and paclitaxel‐dependent induction of premature senescence and pro‐cancerogenic conversion of normal peritoneal mesothelium and fibroblasts

Carboplatin (CPT) and paclitaxel (PCT) are the optimal non‐surgical treatment of epithelial ovarian cancer (EOC). Although their growth‐restricting influence on EOC cells is well known, their impact on normal peritoneal cells, including mesothelium (PMCs) and fibroblasts (PFBs), is poorly understood. Here, we investigated whether, and if so, by what mechanism, CPT and PCT induce senescence of omental PMCs and PFBs. In addition, we tested whether PMC and PFB exposure to the drugs promotes the development of a pro‐cancerogenic phenotype. The results showed that CPT and PCT induce G2/M growth arrest‐associated senescence of normal peritoneal cells and that the strongest induction occurs when the drugs act together. PMCs senesce telomere‐independently with an elevated p16 level and via activation of AKT and STAT3. In PFBs, telomeres shorten along with an induction of p21 and p53, and their senescence proceeds via the activation of ERK1/2. Oxidative stress in CPT + PCT‐treated PMCs and PFBs is extensive and contributes causatively to their premature senescence. Both PMCs and PFBs exposed to CPT + PCT fuel the proliferation, migration, and invasion of established (A2780, OVCAR‐3, SKOV‐3) and primary EOCs, and this activity is linked with an overproduction of multiple cytokines altering the cancer cell transcriptome and controlled by p38 MAPK, NF‐κB, STAT3, Notch1, and JAK1. Collectively, our findings indicate that CPT and PCT lead to iatrogenic senescence of normal peritoneal cells, which paradoxically and opposing therapeutic needs alters their phenotype towards pro‐cancerogenic. It cannot be excluded that these adverse outcomes of chemotherapy may contribute to EOC relapse in the case of incomplete tumor eradication and residual disease initiation. © 2023 The Pathological Society of Great Britain and Ireland.
On‐Site Exposure to Treated Wastewater Effluent Has Subtle Effects on Male Fathead Minnows and Pronounced Effects on Carp

This study tested the hypotheses that (1) exposure to treated Water Reclamation Plant (WRP) effluent will induce biological effects in exposed fish that are consistent with environmental estrogen (EE) exposure; and (2) seasonal differences in effluent composition will moderate biological effects. We conducted seven on‐site exposures using a mobile laboratory. Total estrogenicity of effluents was 10‐ to 20‐fold higher during spring than in fall. Common EEs including steroid estrogens, alkylphenols, and bisphenol‐A were ubiquitous. An unusual spike in total estrogenicity identified a combined sewer overflow event. Fathead minnows (Pimephales promelas) responded to exposure with subtle changes in vitellogenin concentrations and secondary sex characteristics. An opportunity to assess a common carp (Cyprinus carpio) population permanently sustained inside the Stickney WRP revealed pronounced exposure effects, but also the resilience of biological organisms even under long‐term exposure. In contrast to other studies, no histopathological changes were found. The mobile exposure laboratory proved capable of maintaining U.S. Environmental Protection Agency‐recommended exposure conditions while providing flexibility for rapid deployment at multiple sites with minimal operational disruption. Further studies using this platform hold promise to resolve the convoluted interactions between complex effluents and inherent biological complexity.
Advocating for PCR-RFLP as molecular tool within malaria programs in low endemic areas and low resource settings

The road to malaria elimination for low- and middle-income countries is paved with obstacles, including the complexity and high costs of advanced molecular methods for genomic analysis. The usefulness of PCR-RFLP as less complex and affordable molecular surveillance tool in low-endemic malaria regions was assessed in a cross-sectional study conducted in Suriname, currently striving for malaria elimination, but plagued by recent P. vivax outbreaks. Molecular analysis of two highly polymorphic genes Pvmsp-1 F2 and Pvmsp-3α was performed for 49 samples, collected during October 2019 through September 2021 from four different regions with varying malaria transmission risks. RFLP-profiling revealed that outbreak samples from three indigenous villages, almost exclusively, harbored a single clonal type, matching the “Palumeu” lineage previously described in 2019, despite multiple relapses and drug pressure exerted by mass drug administration events, suggesting a limited P. vivax hypnozoite reservoir in Suriname. In contrast, isolates originating from Sophie, a mining area in neighboring French Guiana displayed a highly heterogeneous parasite population consistent with its endemic malaria status, demonstrating the differentiating capacity and thus the usefulness of PCR-RFLP for P. vivax genetic diversity studies. Outbreak reconstruction emphasized the impact of undetected human movement and relapses on reintroduction and resurgence of P. vivax malaria and PCR-RFLP monitoring of circulating parasites guided the roll-out of targeted interventions. PCR-RFLP seems a suitable molecular alternative in low-endemic areas with restricted resources for outbreak analysis, for monitoring the spread or containment of circulating strains and for identification of imported cases or potential foci.
Single-cell genomics reveals region-specific developmental trajectories underlying neuronal diversity in the human hypothalamus

The development and diversity of neuronal subtypes in the human hypothalamus has been insufficiently characterized. To address this, we integrated transcriptomic data from 241,096 cells (126,840 newly generated) in the prenatal and adult human hypothalamus to reveal a temporal trajectory from proliferative stem cell populations to mature hypothalamic cell types. Iterative clustering of the adult neurons identified 108 robust transcriptionally distinct neuronal subtypes representing 10 hypothalamic nuclei. Pseudotime trajectories provided insights into the genes driving formation of these nuclei. Comparisons to single-cell transcriptomic data from the mouse hypothalamus suggested extensive conservation of neuronal subtypes despite certain differences in species-enriched gene expression. The uniqueness of hypothalamic neuronal lineages was examined developmentally by comparing excitatory lineages present in cortex and inhibitory lineages in ganglionic eminence, revealing both distinct and shared drivers of neuronal maturation across the human forebrain. These results provide a comprehensive transcriptomic view of human hypothalamus development through gestation and adulthood at cellular resolution.
Risk of malignancies and chemopreventive effect of statin, metformin, and aspirin in Korean patients with ulcerative colitis: a nationwide population-based study.

Background/Aims We investigated the incidences of overall and site-specific malignancies and chemopreventive effects of statin, metformin, and aspirin in patients with ulcerative colitis. Methods We collected data using the Health Insurance Review and Assessment claims database from January 2007 to April 2020. Results The overall malignancy risk among the 35,189 ulcerative colitis patients was similar to that of the general population (standardized incidence ratio, 0.94; 95% confidence interval, 0.88-1.00). In male patients, standardized incidence ratios were high for thyroid cancer and low for stomach cancer, colorectal cancer, liver cancer, and lung cancer. Concurrently, standard incidence ratios were high for liver cancer and central nervous system cancer in female patients. While 122 cases of colorectal cancer occurred in the study patients, the standardized incidence ratio was 0.83 (95% confidence interval, 0.69-0.99). Treatment for ulcerative colitis was not associated with an increased adjusted hazard ratio, while comorbidities increased it for all malignancies. Treatment for ulcerative colitis was associated with an increased adjusted hazard ratio, while comorbidities did not increase it for colorectal cancer. After adjusting for age, sex, comorbidities, and ulcerative colitis treatment, statins showed a dose-dependent chemopreventive effect for all malignancies (P=0.002), while metformin and aspirin did not show any. Conclusions In ulcerative colitis patients, standardized incidence ratios for all malignancies and colorectal cancer did not increase. Adjusted hazard ratios for all malignancies increased with comorbidities and those for colorectal cancer with ulcerative colitis treatment. Statins have a dose-dependent chemopreventive effect for all malignancies.
Unraveling the impact of sialic acids on the immune landscape and immunotherapy efficacy in pancreatic cancer

Background Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Despite the successful application of immune checkpoint blockade in a range of human cancers, immunotherapy in PDAC remains unsuccessful. PDAC is characterized by a desmoplastic, hypoxic and highly immunosuppressive tumor microenvironment (TME), where T-cell infiltration is often lacking (immune desert), or where T cells are located distant from the tumor islands (immune excluded). Converting the TME to an immune-inflamed state, allowing T-cell infiltration, could increase the success of immunotherapy in PDAC. Method In this study, we use the KPC3 subcutaneous PDAC mouse model to investigate the role of tumor-derived sialic acids in shaping the tumor immune landscape. A sialic acid deficient KPC3 line was generated by genetic knock-out of the CMAS (cytidine monophosphate N-acetylneuraminic acid synthetase) enzyme, a critical enzyme in the synthesis of sialic acid-containing glycans. The effect of sialic acid-deficiency on immunotherapy efficacy was assessed by treatment with anti-programmed cell death protein 1 (PD-1) and agonistic CD40. Result The absence of sialic acids in KPC3 tumors resulted in increased numbers of CD4+ and CD8+ T cells in the TME, and reduced frequencies of CD4+ regulatory T cells (Tregs) within the T-cell population. Importantly, CD8+ T cells were able to infiltrate the tumor islands in sialic acid-deficient tumors. These favorable alterations in the immune landscape sensitized sialic acid-deficient tumors to immunotherapy, which was ineffective in sialic acid-expressing KPC3 tumors. In addition, high expression of sialylation-related genes in human pancreatic cancer correlated with decreased CD8+ T-cell infiltration, increased presence of Tregs, and poorer survival probability. Conclusion Our results demonstrate that tumor-derived sialic acids mediate T-cell exclusion within the PDAC TME, thereby impairing immunotherapy efficacy. Targeting sialic acids represents a potential strategy to enhance T-cell infiltration and improve immunotherapy outcomes in PDAC.
‘Thank you for loving me’: A qualitative study on perceptions of gratitude and their effects in palliative care patients and relatives

Background: Empirical studies suggest that gratitude positively influence the quality of life of palliative patients and relatives. However, the literature is marked by a lack of conceptual clarity about what gratitude is and whether it can bring about individual and social benefits. Aim: This paper explores how palliative care patients and relatives understand gratitude, how discursive representations of gratitude may affect their positions, perceptions and relations, and how to conceptualise gratitude in the palliative context. Design: We examine 33 gratitude letters written by patients and relatives and 25 semi-structured interviews conducted as part of a pilot gratitude intervention study. We use a qualitative approach, thematic analysis, within a conceptual framework of discourse analysis. Settings/participants: Data were collected from 23 patients and 13 relatives recruited through three hospital palliative care services in French-speaking Switzerland. Results: Participants articulate gratitude in five ways: (1) appreciating others; (2) love; (3) need to reciprocate; (4) appreciating the little things; (5) solace amid serious illness. While some of these representations are sources of positive emotions and outlook, wellbeing and hope, others may confirm self-perceptions of powerlessness and burden. These results support a tridimensional conceptualisation of gratitude in palliative care as source of individual benefits, valuing closest relationships and moral obligation. Conclusion: Our study suggests that gratitude is a key to a good (end of) life, whilst highlighting potential negative effects. It could help healthcare professionals to better understand what gratitude means to patients and relatives, which may facilitate awareness and fostering of gratitude in palliative care.