Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-term Effect of Pulp and Paper Mill Effluent on Chemical and Biological Properties of a Heavy Textured Acidic Soil in Assam

Properties of the effluent of Nagaon paper mill at Jagiroad, Assam and typical acid soils receiving either this effluent or shallow tube well (STW) irrigation for 17 years were analyzed. The effluent was alkaline in reaction (pH 7.6, EC 2.5 dS m−1) and contained high levels of dissolved salts, bases and chloride. The pH of the effluent irrigated soil was observed to be 1.3 units higher due to effluent irrigation. Soil salinity (EC) was increased by more than three times. Similarly, CEC, base saturation, total and water soluble basic cations, ESP and SAR were significantly more in the effluent irrigated soil. The chloride concentration of the effluent irrigated soil was 197 mg kg−1 against 43 mg kg−1 observed in the STW irrigated soil. Although, rise in soil pH, CEC and base saturation are desirable for biological activity in acidic soils, the effluent irrigated soils showed rather very low value of microbial biomass carbon content. Overall, the effluent altered the soil characteristics that are not typical of acid soils of this region.
Influence of annealing temperature on the optoelectronic properties of ITZO thin films

In this work, the electrical conductivity and optical transparency of the In–Sn–Zn–O (ITZO) films annealed at different temperatures were investigated. The results show that the ITZO films transformed from amorphous phase to crystalline phase after annealed in the air. The transmittance of the films improves significantly and all exceed 88%. Meanwhile, the annealed ITZO films exhibit a significant enhancement in conductivity. In particular, ITZO film annealed at 650 °C has high electrical conductivity (∼4.94 × 102 S cm−1) and an excellent figure of merit (∼5.94 × 10−4 Ω−1). Moreover, ITZO thin film transistors were prepared and their performance was tested. After annealing, the high electrical properties of the active layer make the gate regulation ability of the thin film transistors degrade. The annealed films with excellent optoelectronic properties can be applied to transparent electrodes.
Liquid biopsy in non-small cell lung cancer—current status and future outlook—a narrative review

Lung cancer ranks first as the cause of cancer-associated deaths gobally. The American Cancer Society estimates for 228,820 new cases and 135,720 deaths from lung cancer in the United States for the year 2020. Targeted treatment options have rapidly emerged for non-small cell lung cancer (NSCLC) within the past decade. Screening for molecular aberrations is mainly done by tissue biopsy. However, in some cases a biopsy is not possible, or patients do not consent to it. Hence, liquid biopsy remains the only option. Relevant data about the topic of liquid biopsy, with a special focus on NSCLC, was obtained via a PubMed search. We included mainly literature published from 2010 onwards, omitting older studies whenever possible. With this review of the literature, we give an overview of different liquid biopsy approaches, as well as their respective advantages and disadvantages. We have reviewed the assessment of epidermal growth factor receptor (EGFR) mutation status in particular, and go into detail with current use of liquid biopsy in everyday clinical practice. Today, liquid biopsy is still infrequently used, depending on the treatment center, but popularity is steadily increasing. Various different approaches are already available, but costs and level of sensitivity significantly differ between techniques. By using liquid biopsy more widely in selected patients, complication rates can be reduced, and constant disease monitoring is made considerably easier.
Outcomes related to anticoagulation management for mechanical valve replacements

Background This study evaluates anticoagulation management and its impact on longitudinal clinical outcomes in patients undergoing mechanical valve replacement. Methods Patients undergoing mechanical mitral valve replacement (MVR) or aortic valve replacement (AVR) from 2010–2018 at a single center were included. Patients were stratified into therapeutic and non-therapeutic anticoagulation groups based on the median percentage of international normalized ratio (INR) values within the reference range (2.0–3.0 for AVR, 2.5–3.5 for MVR) during the first post-operative year. Using Cox regression analysis, comorbidity-adjusted survival and freedom from adverse events were compared. Results Six hundred and fifty-one patients underwent mechanical valve replacement (166 MVR, 485 AVR). Comorbidity-adjusted survival was similar in the MVR and AVR cohorts (P=0.23). There was a median of 27 [interquartile range (IQR): 14–42] INRs drawn per patient in the first post-operative year. The median percentage of INRs within the reference values during the first post-operative year was 42.85% (IQR: 30.77–53.95%), with the majority of non-therapeutic INRs being subtherapeutic (34.51%; n=6,864). There were no significant differences in adjusted survival between the therapeutic and non-therapeutic groups [hazard ratio (HR): 1.12, P=0.73]. Within the first post-operative year, there were no significant differences in stroke, major bleeding, peripheral non-stroke arterial thromboembolism, and readmission for intravenous heparin in the therapeutic and non-therapeutic groups. Conclusions Taking into account relevant comorbidities and valve type, patients with a larger proportion of non-therapeutic INRs during the first post-operative year demonstrated no difference in longitudinal clinical outcomes. Further research into more standardized INR monitoring and potentially expanded INR target ranges for patients undergoing mechanical valve replacement is warranted.
Development and validation of risk and prognostic nomograms for bone metastases in Chinese advanced colorectal cancer patients

Background Bone metastases (BM) from colorectal cancer (CRC) are often accompanied by extraosseous metastases, resulting in a dismal prognosis. The present study aimed to determine the risk factors for BM in metastatic CRC (mCRC) and the prognostic factors for CRC patients with BM. Methods The study was based on a training cohort of 214 mCRC patients (of which, 101 patients had BM) from our center, and a validation cohort of 511 mCRC patients (of which, 173 patients had BM) from another institute. Risk and prognostic nomograms for BM were developed using univariate and multivariate analyses. The goodness of fit, discrimination, and calibration performance of the nomograms were assessed by R2, concordance statistics (C-statistics), and the calibration curve. The results were internally validated using bootstrap resampling in the training cohort, and externally validated in the validation cohort. Results The novel BM risk nomogram comprised seven variables [degree of tumor differentiation, N-stage, serum alkaline phosphatase (ALP), lactate dehydrogenase (LDH), carcinoembryonic antigen (CEA), liver metastasis, and lung metastasis]. It showed good performance, with an R2 of 0.447 and a C-statistic of 0.846 [95% confidence interval (CI), 0.793 to 0.898] in the training cohort, and an R2 of 0.325 and a C-statistic of 0.792 (95% CI, 0.750 to 0.834) in the validation cohort. The optimal cutoff value to identify individuals at low or high risk was 56% probability, with a sensitivity of 71.3% and a specificity of 89.4%. The prognostic nomogram included five factors (tumor differentiation, number of extra-BM organs, number of BM lesions, ALP, and LDH), and had an R2 of 0.284 and a C-statistic of 0.723 (95% CI, 0.657 to 0.789) in the training set. This nomogram was externally validated in the validation cohort, with an R2 of 0.182 and a C-statistic of 0.682 (95% CI, 0.638 to 0.726). Conclusions The developed and validated risk and prognostic nomograms showed good performance for predicting the occurrence of BM in mCRC as well as the prognosis of CRC patients with BM. The risk nomogram can be used as a cost-effective preliminary screening tool prior to bone scanning.
Survival trends for extranodal NK/T-cell lymphoma, nasal type from different anatomical sites: a population-based study

Background Extranodal natural killer/T-cell lymphoma (NKTCL), nasal type mostly involves the upper aerodigestive tract (UAT). NKTCLs derived from the UAT are referred to as nasal NKTCLs, while those without UAT involvement are referred to as extra-nasal NKTCLs. In this study, we aimed to investigate the outcomes and survival trends of NKTCLs from different anatomical sites. Methods Data from the US Surveillance, Epidemiology, and End Results (SEER) database on NKTCL (diagnosed between 1987 and 2016) were retrospectively analyzed. Results A total of 714 patients with NKTCL were included. The median overall survival (OS) and cancer-specific survival (CSS) were 36 and 57 months, respectively. For the entire cohort, the OS was improved from era 1 to era 2 with marginal significance (P=0.0595), however, no improvement was shown in CSS. For nasal NKTCLs, the OS of patients from era 2 was significantly improved compared to that of patients from era 1 (P=0.0244). The OS was significantly improved in non-cavity nasal NKTCLs (P=0.031) but not in nasal cavity NKTCLs (P=0.2982). Significant improvements in OS (P=0.0025) and CSS (P=0.0176) were found in stage I/II non-cavity nasal NKTCLs. For patients with extra-nasal NKTCLs, no difference was found in survival outcomes between the 2 eras. Conclusions We have demonstrated that the outcomes of non-cavity nasal NKTCLs, especially those in stage I/II, have improved in the new era, while the outcomes of nasal cavity NKTCLs and extra-nasal NKTCLs have not improved. Our study highlights the heterogeneity in clinical outcomes and biology among NKTCLs from different sites. More studies are warranted to define the optimal treatments for patients with NKTCLs.
E3 ubiquitin ligase Wwp1 regulates ciliary dynamics of the Hedgehog receptor Smoothened

At the basal state, the ciliary levels of Smo are kept low through the actions of a ciliary localized E2 ubiquitin–conjugating enzyme, Ube2l3, and an E3 ubiquitin ligase, Wwp1. Pathway activation leads to removal of Wwp1 from cilia, allowing Smo to accumulate in cilia and become activated.
Lockdowns, lethality, and laissez-faire politics. Public discourses on political authorities in high-trust countries during the COVID-19 pandemic

This study looks at population response to government containment strategies during initial stages of the COVID-19 pandemic in four high-trust Northern European countries–Denmark, Germany, the Netherlands, and Sweden–with special emphasis on expressions of governmental trust. Sentiment analysis and topic modeling analysis were performed using Twitter data from three phases during the initial European lockdown, and results were compared over time and between countries. Findings show that, in line with existing theory, assertive crisis responses and proactive communication were generally well-received, whereas tentative crisis responses or indications by the authorities that the crisis was manageable were generally met with suspicion. In addition, while government support was high in all countries during the height of the crisis, messages critical of the government as well as conspiracy theories were nevertheless widely circulated. Importantly, countries with the least assertive strategies, rather than clear negative responses, saw heightened polarization of sentiment in the population. Furthermore, in the case of Sweden, a laissez-faire strategy was generally accepted by the population, despite strong criticism from other countries, until mortality rates started to rise. Possible explanations for these findings are discussed with an emphasis of prior trust as a potential explanatory factor. Future research should seek to replicate these findings in other countries with different levels of prior governmental trust or with a different severity of the COVID-19 outbreak than the countries in this study as well as triangulate the findings of this study using alternative methods.
The CCL2-CCR2 astrocyte-cancer cell axis in tumor extravasation at the brain

Astrocyte-secreted CCL2 promotes cancer cell extravasation at the brain via chemotaxis and chemokinesis. Although brain metastases are common in cancer patients, little is known about the mechanisms of cancer extravasation across the blood-brain barrier (BBB), a key step in the metastatic cascade that regulates the entry of cancer cells into the brain parenchyma. Here, we show, in a three-dimensional in vitro BBB microvascular model, that astrocytes promote cancer cell transmigration via their secretion of C-C motif chemokine ligand 2 (CCL2). We found that this chemokine, produced primarily by astrocytes, promoted the chemotaxis and chemokinesis of cancer cells via their C-C chemokine receptor type 2 (CCR2), with no notable changes in vascular permeability. These findings were validated in vivo, where CCR2-deficient cancer cells exhibited significantly reduced rates of arrest and transmigration in mouse brain capillaries. Our results reveal that the CCL2-CCR2 astrocyte-cancer cell axis plays a fundamental role in extravasation and, consequently, metastasis to the brain.
Attenuating glucose metabolism by Fbxw7 promotes Taxol sensitivity of colon cancer cells through downregulating NADPH oxidase 1 (Nox1)

Background Colorectal cancer (CRC), one of the most common malignancies worldwide, is associated with poor survival and has a high mortality rate. Taxol is a chemotherapeutic agent that has been clinically applied as a first-line drug against diverse cancers. Yet, development of drug resistance has become the major challenge for anti-cancer treatments. F-box and WD40 domain protein 7 (Fbxw7) is a known tumor suppressor which is frequently downregulated in cancers. However, the biological roles and mechanisms of Fbxw7 in Taxol resistance are still under investigation. Methods We report that Fbxw7 is significantly inactivated in CRC tumors and cell lines compared with normal tissues and colon cells. Expressions of Fbxw7 and Nox1 were detected from human colon tumors and cells by qRT-PCR and Western blot. Glycolysis rate was assessed by glucose uptake and lactate product assay. Interactions between Fbxw7 and Nox1 were determined by co-immunoprecipitation (Co-IP). Chemosensitivity and resistance of colon cancer cells were determined by MTT assay and Annexin V-FITC assay. Results Overexpression of Fbxw7 sensitized colon cancer cells to Taxol. Moreover, we observed a negative correlation between Fbxw7 and glucose metabolism. From the established Taxol-resistant (TR) cell line from HCT-116, Fbxw7 was found to be markedly downregulated in HCT-116 TR cells. We detected that NADPH oxidase 1 (Nox1), a superoxide-generating NADPH oxidase, is negatively regulated by Fbxw7. The Co-IP assay showed that Fbxw7 interacted with Nox1, which was observed to be significantly upregulated in CRC tissues. Nox1 therefore promotes the Taxol resistance and glucose metabolism of colon cancer cells. Finally, rescue experiments demonstrated that the Fbxw7-promoted Taxol sensitivity was partially through the Nox1-glycolysis axis. Restoration of Nox1 in Fbxw7-overexpressed TR colon cancer cells significantly recovered the Taxol resistance, which could be further overridden by glycolysis inhibition. Conclusions Collectively, this study uncovered that targeting the Fbxw7-Nox1-glucose metabolism axis could be an effective strategy against chemoresistant colon cancer.
A prospective, observational study of fidaxomicin use for Clostridioides difficile infection in France

Objective To describe the characteristics, management and outcomes of hospitalised patients with Clostridioides difficile infection (CDI) treated with and without fidaxomicin. Methods This prospective, multicentre, observational study (DAFNE) enrolled hospitalised patients with CDI, including 294 patients treated with fidaxomicin (outcomes recorded over a 3-month period) and 150 patients treated with other CDI therapies during three 1-month periods. The primary endpoint was baseline and CDI characteristics of fidaxomicin-treated patients. Results At baseline, the fidaxomicin-treated population included immunocompromised patients (39.1%) and patients with severe (59.2%) and recurrent (36.4%) CDI. Fidaxomicin was associated with a high rate of clinical cure (92.2%) and low CDI recurrence (16.3% within 3 months). Clinical cure rates were ≥90% in patients aged ≥65 years, those receiving concomitant antibiotics and those with prior or severe CDI. There were 121/296 (40.9%) patients with adverse events (AEs), 5.4% with fidaxomicin-related AEs and 1.0% with serious fidaxomicin-related AEs. No fidaxomicin-related deaths were reported. Conclusions Fidaxomicin is an effective and well-tolerated CDI treatment in a real-world setting in France, which included patients at high risk of adverse outcomes. Trial registration: Description of the use of fidaxomicin in hospitalised patients with documented Clostridium difficile infection and the management of these patients (DAFNE), NCT02214771, www.ClinicalTrials. gov.
Patient‐incurred costs in a differentiated service delivery club intervention compared to standard clinical care in Northwest Tanzania

Placing all clients with a positive diagnosis for HIV on antiretroviral therapy (ART) has cost implications both for patients and health systems, which could, in turn, affect feasibility, sustainability and uptake of new services. Patient‐incurred costs are recognized barriers to healthcare access. Differentiated service delivery (DSD) models in general and community‐based care in particular, could reduce these costs. We aimed to assess patient‐incurred costs of a community‐based DSD intervention (clubs) compared to clinic‐based care in the Shinyanga region, Tanzania.
People with larger social networks show poorer voice recognition

The way we process language is influenced by our experience. We are more likely to attend to features that proved to be useful in the past. Importantly, the size of individuals’ social network can influence their experience, and consequently, how they process language. In the case of voice recognition, having a larger social network might provide more variable input and thus enhance the ability to recognise new voices. On the other hand, learning to recognise voices is more demanding and less beneficial for people with a larger social network as they have more speakers to learn yet spend less time with each. This paper tests whether social network size influences voice recognition, and if so, in which direction. Native Dutch speakers listed their social network and performed a voice recognition task. Results showed that people with larger social networks were poorer at learning to recognise voices. Experiment 2 replicated the results with a British sample and English stimuli. Experiment 3 showed that the effect does not generalise to voice recognition in an unfamiliar language suggesting that social network size influences attention to the linguistic rather than non-linguistic markers that differentiate speakers. The studies thus show that our social network size influences our inclination to learn speaker-specific patterns in our environment, and consequently, the development of skills that rely on such learned patterns, such as voice recognition.
Taking aim at the perceptual side of motor learning: Exploring how explicit and implicit learning encode perceptual error information through depth vision

Motor learning in visuomotor adaptation tasks results from both explicit and implicit processes, each responding differently to an error signal. While the motor output side of these processes is extensively studied, their visual input side is relatively unknown. We investigated if and how depth perception affects the computation of error information by explicit and implicit motor learning. Two groups of participants threw virtual darts at a virtual dartboard while receiving perturbed endpoint feedback. The Delayed group was allowed to re-aim and their feedback was delayed to emphasize explicit learning, while the Clamped group received clamped cursor feedback which they were told to ignore, and continued to aim straight at the target to emphasize implicit adaptation. Both groups played this game in a highly detailed virtual environment (Depth condition) and in an empty environment (No-Depth condition). The Delayed group showed an increase in error sensitivity under Depth relative to No-Depth conditions. In contrast, the Clamped group adapted to the same degree under both conditions. The movement kinematics of the Delayed participants also changed under the Depth condition, consistent with the target appearing more distant, unlike the Clamped group. A comparison of the Delayed behavioral data with a perceptual task from the same individuals showed that the effect of the Depth condition on the re-aiming direction was consistent with an increase in the scaling of the error distance and size. These findings suggest that explicit and implicit learning processes may rely on different sources of perceptual information. New & Noteworthy We leveraged a classic sensorimotor adaptation task to perform a first systematic assessment of the role of perceptual cues in the estimation of an error signal in the 3D space during motor learning. We crossed two conditions presenting different amounts of depth information, with two manipulations emphasizing explicit and implicit learning processes. Explicit learning responded to the visual conditions, consistent with perceptual reports, while implicit learning appeared to be independent of them.
Developmental Consequences of Defective ATG7-Mediated Autophagy in Humans.

BACKGROUND Autophagy is the major intracellular degradation route in mammalian cells. Systemic ablation of core autophagy-related (ATG) genes in mice leads to embryonic or perinatal lethality, and conditional models show neurodegeneration. Impaired autophagy has been associated with a range of complex human diseases, yet congenital autophagy disorders are rare. METHODS We performed a genetic, clinical, and neuroimaging analysis involving five families. Mechanistic investigations were conducted with the use of patient-derived fibroblasts, skeletal muscle-biopsy specimens, mouse embryonic fibroblasts, and yeast. RESULTS We found deleterious, recessive variants in human ATG7, a core autophagy-related gene encoding a protein that is indispensable to classical degradative autophagy. Twelve patients from five families with distinct ATG7 variants had complex neurodevelopmental disorders with brain, muscle, and endocrine involvement. Patients had abnormalities of the cerebellum and corpus callosum and various degrees of facial dysmorphism. These patients have survived with impaired autophagic flux arising from a diminishment or absence of ATG7 protein. Although autophagic sequestration was markedly reduced, evidence of basal autophagy was readily identified in fibroblasts and skeletal muscle with loss of ATG7. Complementation of different model systems by deleterious ATG7 variants resulted in poor or absent autophagic function as compared with the reintroduction of wild-type ATG7. CONCLUSIONS We identified several patients with a neurodevelopmental disorder who have survived with a severe loss or complete absence of ATG7, an essential effector enzyme for autophagy without a known functional paralogue. (Funded by the Wellcome Centre for Mitochondrial Research and others.).