Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of oxaliplatin‐based chemotherapy on chemosensitivity in patients with peritoneal metastasis from colorectal cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: proof‐of‐concept study

Abstract Background Chemosensitivity testing, including collagen gel droplet‐embedded culture drug sensitivity test, has proven to be a useful tool in therapeutic decision‐making. This retrospective analysis investigated chemosensitivity testing of peritoneal metastases collected during cytoreductive surgery (CRS), and its impact on survival in patients with colorectal cancer. Methods All patients with peritoneal metastasis from colorectal cancer who underwent CRS with or without hyperthermic intraperitoneal chemotherapy (HIPEC) between November 2008 and October 2014 were included. The growth inhibition rate was expressed as the ratio between the image density after treatment (T) and that before treatment (control, C). Tumours with a reduction in T/C ratio of less than 20 per cent were defined as resistant and those with a reduction of 20 per cent or more as sensitive. Groups were compared for overall (OS) and disease‐free (DFS) survival. Results Of 84 eligible patients, 81 received neoadjuvant chemotherapy (NACT), including 56 patients with an oxaliplatin‐based regimen. Mean(s.d.) follow‐up was 23·4(22·9) months. The median overall survival of all patients was 19·0 (i.q.r. 5·7–36·1) months, with a progression‐free survival time of 10·1 (4·5–17·0) months. Patients who received oxaliplatin‐based NACT had significantly altered chemosensitivity to oxaliplatin; only 20 of 51 such patients showed chemosensitivity to oxaliplatin compared with 16 of 24 who did not undergo oxaliplatin‐based NACT (P = 0·046). However, patients who showed chemoresistance to oxaliplatin had similar OS to those with chemosensitivity (18·8 versus 18·1 months; P = 0·835). The choice of HIPEC agents in patients who received oxaliplatin‐based NACT did not significantly influence survival (oxaliplatin versus mitomycin C: median OS 20·6 (10·9–24·8) versus 19·0 (10·5–34·6) months, P = 0·811; DFS 6·6 (2·8–25·7) versus 9·3 (4·1–13·9) months, P = 0·191). Conclusion Patients who had oxaliplatin‐based NACT showed a higher rate of chemoresistance to oxaliplatin at the time of CRS and HIPEC. The impact of chemosensitivity testing on OS remains unclear and needs further investigation.
Promoting mother‐infant relationships and underlying neural correlates: Results from a randomized controlled trial of a home‐visiting program for adolescent mothers in Brazil

Abstract Poverty and teenage pregnancy are common in low‐and‐middle‐income countries and can impede the development of healthy parent‐child relationships. This study aimed to test whether a home‐visiting intervention could improve early attachment relationships between adolescent mothers and their infants living in poverty in Brazil. Analyses were conducted on secondary outcomes from a randomized controlled trial (NCT0280718) testing the efficacy of a home‐visiting program, Primeiros Laços, on adolescent mothers’ health and parenting skills and their infants’ development. Pregnant youth were randomized to intervention (n = 40) or care‐as‐usual (CAU, n = 40) from the first trimester of pregnancy until infants were aged 24 months. Mother‐infant attachment was coded during a mother‐infant interaction when the infants were aged 12 months. Electrophysiological correlates of social processing (mean amplitude of the Nc component) were measured while infants viewed facial images of the mother and a stranger at age 6 months. Infants in the intervention group were more securely attached and more involved with their mothers than those receiving CAU at 12 months. Smaller Nc amplitudes to the mother's face at 6 months were associated with better social behavior at 12 months. Our findings indicate that the Primeiros Laços Program is effective in enhancing the development of mother‐infant attachment.
Molecular phylogeny and new light microscopic data of Metchnikovella spiralis (Microsporidia: Metchnikovellidae), a hyperparasite of eugregarine Polyrhabdina sp. from the polychaete Pygospio elegans

Abstract Abstract Metchnikovellids are a deep-branching group of microsporidia, parasites of gregarines inhabiting the alimentary tract of polychaetes and some other invertebrates. The diversity and phylogeny of these hyperparasites remain poorly studied. Modern descriptions and molecular data are still lacking for many species. The results of a light microscopy study and molecular data for Metchnikovella spiralis Sokolova et al., 2014, a hyperparasite of the eugregarine Polyrhabdina sp. , isolated from the polychaete Pygospio elegans, were obtained. The original description of M. spiralis was based primarily on the analysis of stained preparations and transmission electron microscopy images. Here, the species description was complemented with the results of in vivo observations and phylogenetic analysis based on the SSU rRNA gene. It was shown that in this species, free sporogony precedes sac-bound sporogony, as it occurs in the life cycle of most other metchnikovellids. Spore sacs are entwined with spirally wound cords, and possess only one polar plug. Phylogenetic analyses did not group M. spiralis with M. incurvata, another metchnikovellid from the same gregarine species, but placed it as a sister branch to Amphiacantha. The paraphyletic nature of the genus Metchnikovella was discussed. The taxonomic summary for M. spiralis was emended.
Can you see what I see? A comparison of client and observer perspectives of the alliance and group cohesion in CBT

ABSTRACT Both therapeutic alliance and group cohesion have been identified as “demonstrably effective” relationship elements in therapy. However, the overwhelming majority of process-outcome research has relied on clients as raters of the therapeutic relationship. A lack of convergence between client, therapist, and observer perspectives has raised questions regarding how best to measure relationships in therapy. Interest in observational measures has grown, as they may offer more objective and reliable measurements of process. This study compared the predictive validity of client and observer ratings of the alliance (Agreement and Bond) and group cohesion in the context of group cognitive behaviour therapy (CBT) for anxiety disorders. Results showed that client and observer ratings of process were not significantly correlated, and regarding the alliance, only client-rated Agreement predicted client-rated treatment gains. In contrast, both client and observer-ratings of group cohesion were found to uniquely contribute to treatment outcomes. If replicated, the findings from the present study suggest that (1) while client ratings of alliance consistently predict client-rated outcomes, the predictive validity of observer measures has yet to be established, and (2) both clients and observers provide meaningful and distinct information about group cohesion in therapy.
Polishing the crystal ball: mining multi-omics data in dermatomyositis

Precision medicine, which recognizes and upholds the uniqueness of each individual patient and the importance of discerning these inter-individual differences on a molecular scale in order to provide truly personalized medical care, is a revolutionary approach that relies on the discovery of clinically-relevant biomarkers derived from the massive amounts of data generated by epigenomic, genomic, transcriptomic, proteomic, microbiomic, and metabolomic studies, collectively known as multi-omics. If harnessed and mined appropriately with the help of ever-evolving computational and analytic methods, the collective data from omics studies has the potential to accelerate delivery of targeted medical treatment that maximizes benefit, minimizes harm, and eliminates the “fortune-telling” inextricably linked to the prevailing trial-and-error approach. For a disease such as dermatomyositis (DM), which is characterized by remarkable phenotypic heterogeneity and varying degrees of multi-organ involvement, an individualized approach that incorporates big data derived from multi-omics studies with the results of currently available serologic, histopathologic, radiologic, and electrophysiologic tests, and, most importantly, with clinical findings obtained from a thorough history and physical examination, has immense diagnostic, therapeutic, and prognostic value. In this review, we discuss omics-based research studies in DM and describe their practical applications and promising roles in guiding clinical decisions and optimizing patient outcomes.
Prevalence and Factors Associated With Alcohol Use in Selected Urban Communities in Ibadan, Nigeria

Nigeria is ranked high among African countries in the consumption of alcohol and the national adult per capita consumption was estimated at 12.3litres. Harmful alcohol use is the sixth leading cause of disability and deaths in Nigeria. This study assessed the prevalence and factors associated with alcohol use in selected urban communities in Ibadan, Nigeria. This community-based cross sectional study was conducted among 500 respondents in two selected urban communities in Ibadan, Nigeria. The World Health Organization STEPS tool was used to collect data on socio-demographic characteristics of respondents and the history of alcohol use. Alcohol users were categorized into ever consumed, current consumers, consumers within last 12 months, and frequent consumers within 30 days (low, medium, and high consumers). Chi-square analysis was used to identify factors associated with the different categories of alcohol consumption. The mean age of the respondents was 35.36 ± 12.24 years. Almost one third of the participants (29.0%) reported they had ever consumed alcohol and (13.6%) had consumed alcohol within 30 days prior to the study. Factors significantly associated with the ever-use of alcohol were gender (p = 0.000), and income (p = 0.000). Current use of alcohol had a statistically significant relationship with male gender (p = 0.000). The prevalence of high alcohol use is low in the sample of urban communities studied, and factors influencing include sex, marital status, level of education, income. These results should inform policy decisions to address the alcohol use in urban communities in Southwest Nigeria.
On the function and relevance of alternative 3′‐UTRs in gene expression regulation

Messanger RNA (mRNA) isoforms with alternative 3′‐untranslated regions (3′‐UTRs) are produced by alternative polyadenylation (APA), which occurs during transcription in most eukaryotic genes. APA fine‐tunes gene expression in a cell‐type‐ and cellular state‐dependent manner. Selection of an APA site entails the binding of core cleavage and polyadenylation factors to a particular polyadenylation site localized in the pre‐mRNA and is controlled by multiple regulatory determinants, including transcription, pre‐mRNA cis‐regulatory sequences, and protein factors. Alternative 3′‐UTRs serve as platforms for specific RNA binding proteins and microRNAs, which regulate gene expression in a coordinated manner by controlling mRNA fate and function in the cell. Genome‐wide studies illustrated the full extent of APA prevalence and revealed that specific 3′‐UTR profiles are associated with particular cellular states and diseases. Generally, short 3′‐UTRs are associated with proliferative and cancer cells, and long 3′‐UTRs are mostly found in polarized and differentiated cells. Fundamental new insights on the physiological consequences of this widespread event and the molecular mechanisms involved have been revealed through single‐cell studies. Publicly available comprehensive databases that cover all APA mRNA isoforms identified in many cellular states and diseases reveal specific APA signatures. Therapies tackling APA mRNA isoforms or APA regulators may be regarded as innovative and attractive tools for diagnostics or treatment of several pathologies. We highlight the function of APA and alternative 3′‐UTRs in gene expression regulation, the control of these mechanisms, their physiological consequences, and their potential use as new biomarkers and therapeutic tools.
Impact of environmental temperature and relative humidity on spread of COVID-19 infection in India: a cross-sectional time-series analysis

Abstract Purpose: Coronavirus disease 2019 (COVID-19) has become a serious public health problem worldwide. This study sought to examine the associations of daily average temperature (AT) and relative humidity (ARH) with the percent increase in COVID-19 cases. Methods: Daily confirmed cases and meteorological factors in 38 districts of India were collected between 1st April 2020 to 30th April 2020. Taking a 5-day time lag of average values of the variables and multiple days-samples, we ran multiple models and performed appropriate hypothesis tests to decide the single preferred model for each sample data. Suitable fixed effects (FE) and random effects (RE) models with cluster-robust standard errors were applied to quantify the district-specific associations of meteorological and other variables with COVID-19 cases. Results: All FE models revealed that every one-degree rise in AT led to a decrease in 3.909 points (on average) in percent increase in COVID-19 cases. All RE models showed that with one unit increase in the malaria annual parasite index, there was a significant increase in 10.835 points (on average) in percent increase in COVID-19 cases. In both FE and RE models, ARH was found to be negatively associated with a percent increase in COVID-19 cases, although in half of these models the association was statistically insignificant. Conclusion: Our results indicate that mean temperature, mean relative humidity, and malaria endemicity might have an essential role in the stability and transmissibility of the 2019 novel coronavirus.
Effects of care bundles for patients with pressure ulcers and the impact on self-care efficacy.

OBJECTIVE To investigate the effects of care bundles for patients with pressure ulcers and the impact on self-care efficacy. METHOD A total of 160 patients with pressure ulcers were enrolled and divided into two groups using a lottery method. The control group (n=80) was cared for with routine nursing while the observation group (n=80) was additionally nursed with care bundles for 3 months. Both groups were compared in terms of grading of pressure ulcers, self-care efficacy, pressure ulcer management, awareness rate, and quality of life. RESULTS At 3 months after nursing, the grading of pressure ulcers was significantly improved in both groups. The observation group exhibited higher incidence of pressure ulcers, unstageable and deep tissue injury than the control group (P<0.05). DSES scores were improved in both groups (P<0.05). Scores of daily living, health behavior, compliance behavior, and emotional management in the observation group were higher than those in the control group (P<0.05). The skills of pressure ulcer management were strengthened in both groups (P<0.05). Scores of nutritional support, repositioning, skin care, dressing changes, and pressure ulcer assessment in the observation group were higher than those in the control group (P<0.05). The observation group also exhibited higher scores in terms of diet, pressure ulcer monitoring, lesion staging, complications and knowledge of pressure ulcer triggers than the control group (P<0.05). Quality of life was significantly improved in both groups after 3 months of nursing. PH, RP, BP, GH, VT, SF, RE and MH scores in the observation group were higher than those in the control group (P<0.05). CONCLUSION Care bundles can improve pressure ulcer grading, enhance patient self-care efficacy and skills of pressure ulcer management, and help improve patient awareness rates and quality of life for patients with pressure ulcers, which is worth of promoting.
Detection of human papillomavirus in oropharyngeal squamous cell carcinoma

Worldwide there has been a significant increase in the incidence of oropharyngeal squamous cell carcinoma (OPSCC) etiologically attributed to oncogenic human papillomavirus (HPV). Reliable and accurate identification and detection tools are important as the incidence of HPV-related cancer is on the rise. Several HPV detection methods for OPSCC have been developed and each has its own advantages and disadvantages in regard to sensitivity, specificity, and technical difficulty. This review summarizes our current knowledge of molecular methods for detecting HPV in OPSCC, including HPV DNA/RNA polymerase chain reaction (PCR), loop-mediated isothermal amplification (LAMP), p16 immunohistochemistry (IHC), and DNA/RNA in situ hybridization (ISH) assays. This summary may facilitate the selection of a suitable method for detecting HPV infection, and therefore may help in the early diagnosis of HPV-related carcinoma to reduce its mortality, incidence, and morbidity.
A new subspecies of Trypanosoma cyclops found in the Australian terrestrial leech Chtonobdella bilineata

Abstract Abstract Previously, it was suggested that haemadipsid leeches represent an important vector of trypanosomes amongst native animals in Australia. Consequently, Chtonobdella bilineata leeches were investigated for the presence of trypanosome species by polymerase chain reaction (PCR), DNA sequencing and in vitro isolation. Phylogenetic analysis ensued to further define the populations present. PCR targeting the 28S rDNA demonstrated that over 95% of C. bilineata contained trypanosomes; diversity profiling by deep amplicon sequencing of 18S rDNA indicated the presence of four different clusters related to the Trypanosoma (Megatrypanum) theileri. Novy–MacNeal–Nicolle slopes with liquid overlay were used to isolate trypanosomes into culture that proved similar in morphology to Trypanosoma cyclops in that they contained a large numbers of acidocalcisomes. Phylogeny of 18S rDNA/GAPDH/ND5 DNA sequences from primary cultures and subclones showed the trypanosomes were monophyletic, with T. cyclops as a sister group. Blood-meal analysis of leeches showed that leeches primarily contained blood from swamp wallaby (Wallabia bicolour), human (Homo sapiens) or horse (Equus sp.). The leech C. bilineata is a host for at least five lineages of Trypanosoma sp. and these are monophyletic with T. cyclops; we propose Trypanosoma cyclops australiensis as a subspecies of T. cyclops based on genetic similarity and biogeography considerations.
An Automated Correction Algorithm (ALPACA) for ddPCR Data Using Adaptive Limit of Blank and Correction of False Positive Events Improves Specificity of Mutation Detection.

BACKGROUND Bio-Rad droplet-digital PCR is a highly sensitive method that can be used to detect tumor mutations in circulating cell-free DNA (cfDNA) of patients with cancer. Correct interpretation of ddPCR results is important for optimal sensitivity and specificity. Despite its widespread use, no standardized method to interpret ddPCR data is available, nor have technical artifacts affecting ddPCR results been widely studied. METHODS False positive rates were determined for 6 ddPCR assays at variable amounts of input DNA, revealing polymerase induced false positive events (PIFs) and other false positives. An in silico correction algorithm, known as the adaptive LoB and PIFs: an automated correction algorithm (ALPACA), was developed to remove PIFs and apply an adaptive limit of blank (LoB) to individual samples. Performance of ALPACA was compared to a standard strategy (no PIF correction and static LoB = 3) using data from commercial reference DNA, healthy volunteer cfDNA, and cfDNA from a real-life cohort of 209 patients with stage IV nonsmall cell lung cancer (NSCLC) whose tumor and cfDNA had been molecularly profiled. RESULTS Applying ALPACA reduced false positive results in healthy cfDNA compared to the standard strategy (specificity 98 vs 88%, P = 10-5) and stage IV NSCLC patient cfDNA (99 vs 93%, P = 10-11), while not affecting sensitivity in commercial reference DNA (70 vs 68% P = 0.77) or patient cfDNA (82 vs 88%, P = 0.13). Overall accuracy in patient samples was improved (98 vs 92%, P = 10-7). CONCLUSIONS Correction of PIFs and application of an adaptive LoB increases specificity without a loss of sensitivity in ddPCR, leading to a higher accuracy in a real-life cohort of patients with stage IV NSCLC.
A strategy for proline and glycine mutations to proteins with alchemical free energy calculations

Computation of the thermodynamic consequences of protein mutations holds great promise in protein biophysics and design. Alchemical free energy methods can give improved estimates of mutational free energies, and are already widely used in calculations of relative and absolute binding free energies in small molecule design problems. In principle, alchemical methods can address any amino acid mutation with an appropriate alchemical pathway, but identifying a strategy that produces such a path for proline and glycine mutations is an ongoing challenge. Most current strategies perturb only side chain atoms, while proline and glycine mutations also alter the backbone parameters and backbone ring topology. Some strategies also perturb backbone parameters and enable glycine mutations. This work presents a strategy that enables both proline and glycine mutations and comprises two key elements: a dual backbone with restraints and scaling of bonded terms, facilitating backbone parameter changes, and a soft bond in the proline ring, enabling ring topology changes in proline mutations. These elements also have utility for core hopping and macrocycle studies in computer‐aided drug design. This new strategy shows slight improvements over an alternative side chain perturbation strategy for a set T4 lysozyme mutations lacking proline and glycine, and yields good agreement with experiment for a set of T4 lysozyme proline and glycine mutations not previously studied. To our knowledge this is the first report comparing alchemical predictions of proline mutations with experiment. With this strategy in hand, alchemical methods now have access to the full palette of amino acid mutations.
Serum creatinine as a predictor of mortality in patients readmitted to the intensive care unit after cardiac surgery: a retrospective cohort study in China

Background Patients readmitted to the intensive care unit (ICU) after cardiac surgery have a high mortality rate. The relationship between renal function and in-hospital mortality in readmitted patients has not been well demonstrated. Methods We retrospectively evaluated cardiac surgery patients who were readmitted to the ICU at least once. Data on serum creatinine levels before surgery and on the day of ICU readmission were collected. The estimated glomerular filtration rate (eGFR) was calculated according to the creatinine-based Chronic Kidney Disease-Epidemiology Collaboration equation. We used logistic regression models and restricted cubic spline curves with four knots (5%, 35%, 65%, 95%) to investigate the relationship between renal function indicators and mortality. Results Of the 184 patients evaluated, 30 patients died during hospitalization, yielding a mortality rate of 16.30%. Cardiac dysfunction (n=84, 45.65%) and respiration disorder (n=51, 27.72%) were the most common reasons for ICU readmission. Creatinine [odds ratio (OR): 1.14, 95% confidence interval (CI): 1.07–1.25] and eGFR (OR: 0.95, 95% CI: 0.93–0.98) were independently associated with in-hospital mortality after adjusting for various confounders. Both creatinine level and eGFR had a linear association with in-hospital mortality (P for non-linearity ˃0.05). Conclusion Renal function is significantly associated with the in-hospital mortality of patients readmitted to the ICU after cardiac surgery, as evidenced by the independent correlation of both creatinine and eGFR with in-hospital mortality.