Miracle-dz/UniFAR-FTUs huggingface dataset:
Deficit in knee extension strength following anterior cruciate ligament reconstruction is explained by a reduced neural drive to the vasti muscles

The persistence of quadriceps weakness represents a major concern following anterior cruciate ligament reconstruction (ACLR). The underlying adaptations occurring in the activity of spinal motoneurons are still unexplored. This study examined the discharge patterns of large populations of motor units (MUs) in the vastus lateralis (VL) and vastus medialis muscles following ACLR. Nine ACLR individuals and 10 controls performed unilateral trapezoidal contractions of the knee extensor muscles at 35%, 50% and 70% of the maximal voluntary isometric force (MVIF). High‐density surface electromyography (HDsEMG) was used to record the myoelectrical activity of the vasti muscles in both limbs. HDsEMG signals were decomposed with a convolutive blind source separation method and MU properties were extracted and compared between sides and groups. The ACLR group showed a lower MVIF on the reconstructed side compared to the contralateral side (28.1%; P < 0.001). This force deficit was accompanied by reduced MU discharge rates (∼21%; P < 0.05), lower absolute MU recruitment and derecruitment thresholds (∼22% and ∼22.5%, respectively; P < 0.05) and lower input–output gain of motoneurons (27.3%; P = 0.009). Deficits in MU discharge rates of the VL and in absolute recruitment and derecruitment thresholds of both vasti MUs were associated with deficits in MVIF (P < 0.05). A strong between‐side correlation was found for MU discharge rates of the VL of ACLR individuals (P < 0.01). There were no significant between‐group differences (P > 0.05). These results indicate that mid‐ to long‐term strength deficits following ACLR may be attributable to a reduced neural drive to vasti muscles, with potential changes in excitatory and inhibitory synaptic inputs.
Theoretical and in vivo investigations of morphology and concentration of gold nanoparticles for laser surgery

Precise control of the thermal damage is critical during thermal therapy with the assistance of gold nanoparticles, which depends on the laser parameters and characteristics of gold nanoparticles. However, the current understanding of the relationship between the gold nanoparticles/incident laser light and the efficiency of photothermal therapy is limited, which should be studied systematically.
Prospective Study of Nocturnal Desaturation in Patients Receiving Home Oxygen Therapy

Objective Nocturnal desaturation is common in patients with chronic respiratory disease and often worsens the prognosis. Therefore, it should be diagnosed accurately and appropriately treated. The aim of this study was to clarify the diversity of nocturnal desaturation. Methods We prospectively enrolled 58 outpatients diagnosed with chronic respiratory disease receiving home oxygen therapy and measured nocturnal SpO2 using a portable oximeter. We classified nocturnal desaturation (3% decrease in SpO2 from baseline) into three patterns: periodic pattern (desaturation duration of <655 seconds), sustained pattern (desaturation duration of ≥655 seconds), and intermittent pattern (desaturation and recovery of SpO2 repeated with a cycle of several minutes). Results Nocturnal hypoxemia (SpO2 ≤88% for more than 5 minutes) was found in 23.8% of patients. The percentage of patients with chronic obstructive pulmonary disease (COPD) was significantly higher in the nocturnal hypoxemia group than in the non-hypoxemia group (80% vs. 40.6%, p=0.03). Desaturation with a periodic pattern was found in 81% of patients, desaturation with a sustained pattern was found in 40.5% of patients, and desaturation with an intermittent pattern was found in 59.5% of patients. In patients with COPD, desaturation with a periodic pattern was found in 85.7%, desaturation with a sustained pattern was found in 47.6%, and desaturation with an intermittent pattern was found in 57.1%. Conclusion The SpO2 waveform of nocturnal hypoxemia was able to be classified into three patterns. Suitable treatment for each pattern might improve the prognosis of these patients.
Effect of Synthesis Methods and Conditions on Properties and Applications of Carbon Dots for the Detection of Potential Water Contaminants: A Review

Abstract The worldwide pollution of water bodies by potential contaminants such as heavy metals, dyes, and pesticides etc. have severely affected the entire eco-system due to their toxic mobility and tough degradation in water. Consequently, there is a requirement to develop cost-competitive and easily handleable sensing materials which can detect targets sensitively and with selectivity. Among the low-cost sensory materials, carbon dots (CDs) constitute an important class of carbon nanomaterial with unique photostability, electronic and fluorescent properties. This review is an effort to comprehend the recent improvements in the sensing applications of CDs with prominence on synthetic routes, the effect of various synthesis parameters on physical properties (quantum yield, size range), detection mechanisms, and detection parameters (limit of detection, interference etc.). Particularly, the scope and progress for the detection of potential water contaminants using CDs have been explored and a holistic view of mechanisms of their detection has been included. Graphical Abstract Holistic view of mechanisms for different types of signals generated by CDs.
Cost-effectiveness analysis of the first‐line EGFR‐TKIs in patients with advanced EGFR-mutated non-small-cell lung cancer

ABSTRACT Aim To evaluate the cost-effectiveness of first-line treatments, such as erlotinib, gefitinib, afatinib, dacomitinib, and osimertinib, for patients diagnosed with stage IIIB/IV NSCLC harboring EGFR mutations. Materials & methods A partitioned survival model was developed to estimate quality-adjusted life-year (QALY) and incremental cost-effectiveness ratio (ICER) from the perspective of the Spanish National Health System. Two Bayesian NMAs were performed independently, by using the polynomial fraction method to fit Kaplan–Meier curves for overall survival and progression-free survival. Deterministic and probabilistic sensitivity analyses were performed to evaluate the uncertainty. Results The ICER was calculated for the four first-line treatments by comparing them with gefitinib, and the ratios obtained were as follows: €166,416/QALY for osimertinib, €183,682/QALY for dacomitinib, €167,554/QALY for afatinib, €36,196/QALY for erlotinib. It was seen that patients who received osimertinib presented higher QALYs (0.49), followed by dacomitinib (0.33), afatinib (0.32), erlotinib (0.31), and gefitinib (0.28). Conclusions Gefitinib is the most cost-effective treatment. In terms of QALYs gained, Osimertinib was more effective than all other TKIs. Nevertheless, with a Spanish threshold of €24,000/QALY, the reduction in the acquisition cost of osimertinib will have to be greater than 70%, to obtain a cost-effectiveness alternative.
Mobilization of soil phosphate after 8 years of warming is linked to plant phosphorus‐acquisition strategies in an alpine meadow on the Qinghai‐Tibetan Plateau

Phosphorus (P) is essential for productivity of alpine grassland ecosystems, which are sensitive to global warming. We tested the hypotheses that (1) mobilized ‘calcium‐bound inorganic P’ (Ca‐Pi) is a major source of plant‐available P in alpine meadows with alkaline soils after long‐term warming, (2) mobilization of Ca‐Pi is linked to effective plant carboxylate‐releasing P‐acquisition strategies under warming, and (3) the mobilization is also related to plant nitrogen (N)‐acquisition. We conducted an 8‐year warming experiment in an alpine meadow (4635 m above sea level) on the Qinghai‐Tibetan Plateau. A significant increase in P concentration in both aboveground and belowground biomass indicates an increased mobilization and assimilation of P by plants under warming. We observed a significant decrease in Ca‐Pi, no change in moderately‐labile organic P, and an increase in highly resistant organic P after warming. There was no increase in phosphatase activities. Our results indicate that Ca‐Pi, rather than organic P was the major source of plant‐available P for alpine meadows under warming. Higher leaf manganese concentrations of sedges and forbs after warming indicate that carboxylates released by these plants are a key mechanism of Ca‐Pi mobilization. The insignificant increase in Rhizobiales after warming and the very small cover of legumes show a minor role of N‐acquisition strategies in solubilizing phosphate. The insignificant change in relative abundance of mycorrhizal fungi and bacteria related to P cycling after warming shows a small contribution of microorganisms to Ca‐Pi mobilization. The significant increase in leaf N and P concentrations and N:P ratio of grasses and no change in sedge leaf N:P ratio reflect distinct responses of plant nutrient status to warming due to differences in P‐acquisition strategies. We highlight the important effects of belowground P‐acquisition strategies, especially plant carboxylate‐releasing P‐acquisition strategies on responses of plants to global changes in alpine meadows.
Duloxetine ameliorates valproic acid‐induced hyperactivity, anxiety‐like behavior, and social interaction deficits in zebrafish

Syndromic autism spectrum disorders (ASDs) are characterized by impaired social communication and repetitive/stereotyped behaviors. Currently available therapeutic agents against ASD have limited efficacy. Thus, searching for novel and effective drugs ameliorating core symptoms, in particular social deficits, is of utmost importance. Duloxetine (DLX), an antidepressant that has been identified as an agonist mimetic for the cell adhesion molecule L1, exhibits beneficial functions in vitro and in vivo. Therefore, in this study, we focused on the rapid and persistent neuroprotective function of DLX following valproic acid (VPA)‐triggered hyperactivity, anxiety‐like behavior and social deficits in zebrafish. Embryonic exposure to VPA reduced survival in a dose‐ and time‐dependent manner, delayed hatching, and also resulted in a significant number of malformed larvae. After initial dose–response experiments in zebrafish larvae, 10 μM VPA exposure between 0.33 and 4.5 days post fertilization (dpf) was identified as an effective concentration that led to an early and persistent ASD‐like phenotype in zebrafish. ASD‐like elevated acetylcholine esterase (AChE) activity and reduced Akt–mTOR signaling was observed in zebrafish whole brain. Acute administration of DLX (4.5–6 dpf) reduced the VPA‐induced ASD‐like phenotype in zebrafish larvae. Additionally, such early‐life acute DLX treatment had long‐term effects in ameliorating social impairments, hyperactivity, and anxiety‐like behaviors through adulthood. This was accompanied by reduced AChE activity and by normalized Akt–mTOR signaling. Overall, DLX treatment showed a long‐term therapeutic effect on autistic‐like behaviors, and alteration of AChE activity and Akt–mTOR signaling were identified as crucial in the VPA‐induced ASD zebrafish model.
Chaphamaparvovirus antigen and nucleic acids are not detected in kidney tissues from cats with chronic renal disease or immunocompromised cats

Chronic kidney disease (CKD) is a common cause of morbidity and mortality in domestic cats, but the cause is still largely elusive. While some viruses have been associated with this disease, none have been definitively implicated as causative. Recently, Rodent chaphamaparvovirus 1 was recognized as the cause of murine inclusion body nephropathy, a disease reported for over 40 years in laboratory mice. A novel virus belonging to the same genus, Carnivore chaphamaparvovirus 2, was recently identified in the feces of cats with diarrhea. The goal of this study was to investigate the possible role of chaphamaparvoviruses including members of Rodent chaphamaparvovirus 1 and Carnivore chaphamaparvovirus 2 in the development of feline CKD. The presence of these viruses was retrospectively investigated in formalin-fixed paraffin-embedded feline kidney samples using polymerase chain reaction, in situ hybridization, and immunohistochemistry. Cats were divided into 3 groups: normal (N = 24), CKD (N = 26), and immunocompromised (N = 25). None of the kidney tissues from any of the 75 cats revealed the presence of chaphamaparvovirus DNA, RNA, or antigen. We conclude that viruses belonging to the chaphamaparvovirus genus are unlikely to contribute to the occurrence of feline CKD.
Does minimally invasive liver resection improve long-term survival compared to open resection for hepatocellular carcinoma? A systematic review and meta-analysis.

INTRODUCTION Minimally invasive liver surgery for hepatocellular carcinoma has gained widespread interest as an alternative to conventional open liver surgery. However, long-term survival benefits of this approach seem unclear. This meta-analysis was conducted to investigate long-term survival following minimally invasive liver surgery. METHOD A systematic review was performed to identify studies comparing long-term survival after minimally invasive liver surgery and open liver surgery until January 2020. The I2 test was used to test for statistical heterogeneity and publication bias was assessed using Egger test. Random-effects meta-analysis was performed for all-cause 5-year (main outcome) and 3-year mortality, and disease-specific 5-year and 3-year mortality. Meta-regression was performed for the 5-year and 3-year survival outcomes with adjustment for study factors (region, design), annual center volume, patient factors (American Society of Anesthesiologists (ASA) grade, gender, age, body mass index, cirrhosis, tumor size, and number), and resection extent. Sensitivity analyses were performed on studies by study year, region, annual center volume, and resection type. RESULT The review identified 50 relevant studies including 13,731 patients undergoing liver resection for hepatocellular carcinoma of which 4071 (25.8%) underwent minimally invasive liver surgery. Pooled analysis revealed similar all-cause (odds ratio: 0.83, 95% confidence interval: 0.70-1.11, p = 0.3) and disease-specific (odds ratio: 0.93, 95% confidence interval: 0.80-1.09, p = 0.4) 5-year mortality after minimally invasive liver surgery compared with open liver surgery. Sensitivity analysis of published studies from 2010 to 2019 demonstrated a significantly lower disease-specific 3-year mortality (odds ratio: 0.75, 95% confidence interval: 0.59-0.96, p = 0.022) and all-cause 5-year mortality (odds ratio: 0.63, 95% confidence interval: 0.50-0.81, p = 0.002). Meta-regression identified no confounding factors in all analyses. CONCLUSIONS Improvement in minimally invasive liver surgery techniques over the past decade appears to demonstrate superior disease-specific mortality with minimally invasive liver surgery compared to open liver surgery. Therefore, minimally invasive liver surgery can be recommended as an alternative surgical approach for hepatocellular carcinoma.
Periodontal disease and a poor response to periodontal treatment were associated with an increased risk of incident diabetes: a longitudinal cohort study in Sweden.

AIM To investigate whether periodontal disease or the response to periodontal treatment could influence the risk of future diabetes. MATERIALS AND METHODS 8,983 individuals referred for periodontal treatment between 1980 and 2015 were eligible. Diabetes incidence was obtained from the Swedish registers for cause of death, hospital discharge, and national diabetes registers. Data concerning treatment outcome 1 year after treatment were available for 5,258 individuals. Poor response to treatment was defined as having >10% sites with probing pocket depth ≥5 mm deep and bleeding on probing (BOP) at ≥ 20% of the sites. RESULTS 1117 incident cases of diabetes occurred among the 8,983 individuals during a median follow-up of 21.3 years. Number of teeth and BOP at baseline were significantly associated with incident diabetes in a dose-dependent manner after adjusting for age, sex, smoking, education level and civil status (incident rate ratio=IRR of 0.88 (95% CI 0.84-0.93), p <0.001 and IRR of 1.06, (95% CI 1.02-1.11), p=0.003). Poor response to treatment (14%) associated with an increased risk (37%) for future diabetes (95% CI 1.12-1-1.68, p=0.002) compared with good responders. CONCLUSION Periodontal disease with increased tooth loss and BOP as well as poor response to treatment was associated with an increased risk for diabetes.
Evaluation of Oxidative Stress, Apoptosis, and Expression of MicroRNA-208a and MicroRNA-1 in Cardiovascular Patients.

Background MicroRNA expression signature and reactive oxygen species (ROS) production have been associated with the development of cardiovascular diseases (CVDs). This study aimed to evaluate oxidative stress, inflammation, apoptosis, and the expression of miRNA-208a and miRNA-1 in cardiovascular patients. Methods The study population included four types of patients (acute coronary syndromes (ACS), myocardial infarction (MI), arrhythmia, and heart failure (HF)), with 10 people in each group, as well as a control group. Quantitative real-time PCR was performed to measure mir-208 and miR-1 expression, the mRNAs of inflammatory mediators (TNFα, iNOS/eNOS), and apoptotic factors (Bax and Bcl2). XOX, MDA, and antioxidant enzymes (CAT, SOD, and GPx) were measured by ZellBio GmbH kits by an ELISA Reader. Results The results showed significant decreases in the activity of antioxidant enzymes (CAT, SOD, and Gpx) and a significant increase in the activity of the MDA and XOX in cardiovascular patients. Significant increases in IL-10, iNos, iNOS / eNOS, and TNF-α in cardiovascular patients were also observed. Also, a significant increase in the expression of miR-208 (HF> arrhythmia> ACS> MI) and a significant decrease in the expression of miR-1 (ACS> arrhythmia> HF> MI) were found in all four groups in cardiovascular patients. Conclusion The results showed increases in oxidative stress, inflammation, apoptotic factors, and in the expression of miR-208a in a variety of cardiovascular patients (ACS, MI, arrhythmia, and HF). It is suggested that future studies determine the relationships that miR-1, miR-208, and oxidative stress indices have with inflammation and apoptosis.
Predicting Parkinson’s Disease and Its Pathology via Simple Clinical Variables

Background: Parkinson’s disease (PD) is a chronic, disabling neurodegenerative disorder. Objective: To predict a future diagnosis of PD using questionnaires and simple non-invasive clinical tests. Methods: Participants in the prospective Kuakini Honolulu-Asia Aging Study (HAAS) were evaluated biannually between 1995–2017 by PD experts using standard diagnostic criteria. Autopsies were sought on all deaths. We input simple clinical and risk factor variables into an ensemble-tree based machine learning algorithm and derived models to predict the probability of developing PD. We also investigated relationships of predictive models and neuropathologic features such as nigral neuron density. Results: The study sample included 292 subjects, 25 of whom developed PD within 3 years and 41 by 5 years. 116 (46%) of 251 subjects not diagnosed with PD underwent autopsy. Light Gradient Boosting Machine modeling of 12 predictors correctly classified a high proportion of individuals who developed PD within 3 years (area under the curve (AUC) 0.82, 95%CI 0.76–0.89) or 5 years (AUC 0.77, 95%CI 0.71–0.84). A large proportion of controls who were misclassified as PD had Lewy pathology at autopsy, including 79%of those who died within 3 years. PD probability estimates correlated inversely with nigral neuron density and were strongest in autopsies conducted within 3 years of index date (r = –0.57, p < 0.01). Conclusion: Machine learning can identify persons likely to develop PD during the prodromal period using questionnaires and simple non-invasive tests. Correlation with neuropathology suggests that true model accuracy may be considerably higher than estimates based solely on clinical diagnosis.
Association of IL-15 and IP-10 Serum Levels with Cytomegalovirus Infection, CMV Viral Load and Cyclosporine Level after Kidney Transplantation.

Background Cytomegalovirus (CMV) infection is the most common complications following kidney transplantation. Natural killer (NK) cells demonstrated critical anti-viral role in controlling and elimination of CMV after transplantation. Interleukin-15 (IL-15) is a pleiotropic cytokine that promotes the activity of NK cells and strengthens the acquired immune system. Also, IP10 (CXCL10) is a chemotactic factor which regulates NK cell recruitment and antiviral immune response. We aimed to determine the correlation between the serum levels of IL-15 and IP-10 cytokines with CMV infection, CMV viral load, and cyclosporine as a major immunosuppressive treatment after transplantation. Methods Fifty-eight kidney transplant recipient patients without evidence of CMV virus disease before transplantation surgery were included in the study. From the day of transplant surgery, the patients were evaluated based on the presence of CMV Ag pp65, CMV viral load, serum levels of IL-15 & IP-10, Cyclosporine levels (C0 & C2), Glomerular Filtration Rate (GFR), and hematological & biochemical Index, up to 75 days. Results Comparison analysis of serum levels of IL-15 and IP-10 showed no significant association with CMV infection in kidney transplant recipients. In addition, CMV viral load and cyclosporine levels at C0 and C2 did not affect patients' IL-15 and IP-10 levels. Conclusion The levels of IP-10 and IL-15 cytokines are not affected with CMV infection, even if a viral infection occurs in the early days after transplantation or long afterwards. In addition, taking the different levels of cyclosporine did not affect the cytokines levels. Other mechanisms may play a role in maintaining the levels of these cytokines.
A 15-year pheochromocytoma and paraganglioma experience in a single centre: a Singapore perspective

Introduction: Pheochromocytomas (PCC) and paragangliomas (PGL) are rare endocrine tumours. The objective of this study was to describe our experience with these two entities in a Singapore population. Methods: We identified patients with positive histopathological confirmations of PCC and PGL who were treated at a tertiary Singapore hospital between January 2000 and December 2015. The results were analysed for clinical presentations, treatment and long-term outcomes. Results: A total of 27 cases (20 PCC, 7 PGL) were identified over a 15-year period. One case of PGL developed bilateral disease on follow-up. There were 17 male and 10 female patients with a median age of 57 (range 24–77) years. A positive family history was uncommon and present in only 3.7% of patients. Uniquely, the top three presenting symptoms were abdominal discomfort, palpitations and diaphoresis. Despite adequate preoperative preparation, intraoperative haemodynamic instability occurred in 70.4% and early postoperative hypotension occurred in 11.1% of patients. After surgery, hypertension was resolved in 41.2% (7/17) and diabetes mellitus in 60% (3/5). Disease recurrence was reported in 22.2% and distant metastases in 14.8%. At the end of the follow-up period (median 35 [range 3–148] months), 70.4% were still alive. Conclusion: PCC and PGL can present with a wide range of symptoms. Intraoperative haemodynamic instability was frequent despite good preoperative preparation. Disease recurrences and metastasis occurred in up to one-fifth of the patients. Genetic screening should be offered to patients with PCC and PGL.