Miracle-dz/UniFAR-FTUs huggingface dataset:
The activity level of follicular helper T cells in the peripheral blood of osteosarcoma patients is associated with poor prognosis

ABSTRACT Osteosarcoma (OS) is solid tumors with high malignancy and incidence starting in the bones. OS pathogenesis has been proved to be closely associated with immune imbalance, and follicular helper T cells (Tfh) significantly affect host humoral immune homeostasis. However, there are few reports on the effect of Tfh cell activation on the prognosis of OS patients. Hence, this investigation on the changes in the proportion of peripheral blood Tfh cells in OS patients, and the relationship between their activity level and OS prognosis. We collected peripheral blood from patients with OS, benign bone tumor (BT group) and healthy subjects (Healthy group), respectively. The number of CD4+CXCR5+ Tfh cell in peripheral blood was measured by flow cytometry and correlation analysis between its activity and OS clinicopathological characteristics was carried out. The data showed that in comparison with the BT and Healthy groups, higher proportion and activation level of peripheral blood CD4+CXCR5+ Tfh cells in CD4+ T cells were found in the OS group. In OS patients, increases of the proportion and activity level of Tfh cells were associated with poorly differentiated OS and tumor metastasis. Additionally, Kaplan-Meier and Cox regression analysis showed a longer overall survival in patients with low proportion of peripheral blood CD4+CXCR5+ Tfh cells in CD4+ T cells, and their activation level may be a prognostic factor in OS patients. In conclusion, peripheral blood CD4+CXCR5+ Tfh cell activation in OS patients was associated with a poor prognosis. This study provided ideas for improving the clinical treatment of OS patients. Graphical abstract
Mapping of corneal birefringence in thin and asymmetric keratoconus corneas with ultrahigh-resolution polarization-sensitive OCT

The phase retardation across healthy and thin corneas (no clinical disease) and asymmetric and bilateral keratoconus clearly showed distinct structural differences not observed in conventional tomography. Purpose: To evaluate phase retardation (PR) across healthy eyes and eyes with thin corneas (<500 μm) and with asymmetric and bilateral keratoconus (KC). Setting: Narayana Nethralaya Eye Hospital, Bangalore, India. Design: Observational cross-sectional. Methods: There were 4 eye groups: healthy eyes (Group 1; n = 10 eyes), eyes with thin corneas and no clinical disease (Group 2; n = 10 eyes), eyes with asymmetric KC (Group 3; n = 5 eyes), and eyes with clinical KC (Group 4; n = 15 eyes). All eyes were imaged with polarization-sensitive optical coherence tomography (PS-OCT), MS-39, and Corvis-ST. Using PS-OCT, PR was analyzed in annular regions. The anterior (A-E) and Bowman (E-B) wavefront aberrations, epithelial Zernike indices (EZI), total corneal thickness, Corvis biomechanical index (CBI), total biomechanical index (TBI), and Belin-Ambrósio overall deviation index (BAD-D) were analyzed. Results: Only CBI, TBI, BAD-D, A-E and E-B aberrations, EZI, and total corneal thickness distributions of Groups 1 (n =10), 2 (n =10), and 3 (n =5) were similar (P > .05) but not CCT (P < .05). PR distributions clearly showed that the eyes in Groups 1, 2, and 3 had a normal corneal birefringence unlike Group 4 (n = 10) eyes (P < .05). The PR map was similar to the preferred orientations of collagen fibers seen in X-ray diffraction ex vivo studies of corneal stroma. Conclusions: PR distributions may eliminate the uncertainty associated with the stromal status of thin and asymmetric KC corneas. Group 2 and 3 eyes appeared as healthy because of normal corneal birefringence at the time of imaging, but a longitudinal follow-up of these eyes with PS-OCT may assist in early detection of onset of disease.
Effects of transcranial direct current stimulation over the right dorsolateral prefrontal cortex on fairness-related decision-making

Abstract Neuroimaging studies suggest that the right dorsolateral prefrontal cortex (rDLPFC) is an important brain area involved in fairness-related decision-making. In the present study, we used transcranial direct current stimulation (tDCS) over the rDLPFC to investigate the effects of changed cortical excitability on fairness norm enforcement in social decision-making. Participants received anodal, cathodal or sham stimulation before performing a modified ultimatum game task, in which participants were asked to accept or reject the proposer’s offer and self-rate the intensity of their anger at offers on a 7-point scale. The results showed that the rejection rate of unfair offers and anger level were higher in the anodal compared to the sham and cathodal groups and that the level of anger at unfair offers can predict the rejection rate. Furthermore, the fairness effect of RTs was more prominent in the anodal group than in the sham and cathodal groups. Our findings validate the causal role of the rDLPFC in fairness-related decision-making through tDCS, suggesting that strengthening the rDLPFC increases individuals’ reciprocal fairness in social decision-making, both in subjective rating and behaviors.
Stress predicts depression symptoms for women living with bipolar disorder during the menopause transition

Abstract Objective: Although sleep disturbance is an important feature in bipolar disorder, the relationship between mood symptoms, sleep disturbances, and hot flash symptom severity during menopause for women with bipolar disorder is largely unknown. Methods: Women with bipolar disorder (n = 100) who were categorized as perimenopausal using the STRAW and Monash criteria took part in an international online survey. The survey contained questions on history of reproductive health; the clinical course of bipolar disorder; menopausal symptoms (Menopause Rating Scale [MRS]); depression, anxiety, and stress (Depression Anxiety and Stress Scale—21) and the Altman Mania Rating Scale. Results: MRS sleep problems and hot flash severity were positively correlated with each other and with depression, anxiety, and stress symptoms. Mania scores were not significantly correlated with sleep or hot flash severity scores. A stepwise regression analysis on depression symptoms, using MRS sleep disturbance and MRS hot flash severity scores as predictors with anxiety and stress symptoms in the model, found that stress alone predicted 40% of the variance in total depression scores. Conclusion: Stress plays an important role in the experience of depression for women living with bipolar disorder during the perimenopausal phase. More research is needed to determine if stress management programs may be helpful for women living with bipolar disorder during this time of life and if these in turn, may improve depressive symptoms.
Seroprevalence of SARS-CoV-2 Neutralizing Antibodies among Blood Donors in Ho Chi Minh City, Vietnam, August–November 2020

ABSTRACT. Relatively little is known about the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibodies and COVID-19-related behaviors in the general population in Vietnam, where the first case of COVID-19 was detected on January 22, 2020. We surveyed a group of 885 blood donors at community blood donation sessions in Ho Chi Minh City from August 27 to November 7, 2020. Blood was collected to test for SARS-CoV-2 IgG antibodies using the plaque reduction neutralization test. We adjusted the seroprevalence by weight for ages 18 to 59 years old obtained from the 2019 population census. The weighted seroprevalence estimate for SARS-CoV-2 neutralizing IgG antibodies was 0.20% (95% CI, 0.05–0.81). Reports of usually or always using a mask in public places were observed at high levels of 28.6% and 67.5%, respectively. The percentages of usually or always washing hands with soap or disinfecting with hand sanitizer after touching items in public places were 48.0% and 37.6%, respectively. Although our findings suggest undocumented exposure to the virus, the seroprevalence of SARS-CoV-2 IgG antibodies among blood donors was low in this city.
Role of Estrogen and Its Receptors in Adipose Tissue Glucose Metabolism in Pre- and Postmenopausal Women

Abstract Context Reduced estrogen levels in postmenopausal women predispose them to metabolic side effects, including insulin resistance and type 2 diabetes; however, the cellular mechanisms are not well understood. Objective This work aimed to study the expression of estrogen receptors in adipose tissue from pre- and postmenopausal women and the effects of estradiol (E2) on glucose uptake of adipocytes. Methods Subcutaneous (SAT) and visceral adipose tissue (VAT) obtained from pre- and postmenopausal women (19-51 and 46-75 years old, respectively) were used to measure gene expression of ESR1 and ESR2. SAT tissue was incubated with E2, and glucose uptake and estrogen receptor levels were measured. Polymorphisms in ESR1 and ESR2 were addressed in public databases to identify single nucleotide polymorphisms associated with metabolic traits. Results ESR2 expression was lower in pre- vs postmenopausal women, corresponding to lower ESR1:ESR2 gene expression ratio in postmenopausal women. In premenopausal women, the expression of ESR1 was higher in VAT than in SAT. In both pre- and postmenopausal women, ESR2 expression was lower in VAT than in SAT. In late, but not pre- or early postmenopausal women, E2 reduced glucose uptake and GLUT4 protein and increased expression of ESR2. ESR1 polymorphisms were associated with weight, body fat distribution, and total cholesterol, and ESR2 polymorphisms were associated with total cholesterol and triglyceride levels and with body fat percentage. Conclusion E2 inhibits glucose utilization in human adipocytes in late postmenopausal women. Changes in glucose utilization over time since menopause may be explained by a lower ESR1:ESR2 ratio. This can have clinical implications on the timing of estrogen treatment in postmenopausal women.
Extracorporeal membrane oxygenation for respiratory failure in children: the years before and after the 2009 H1N1 pandemic

Objective: To evaluate whether there was any impact on the number of pediatric extracorporeal membrane oxygenation runs and survival rates in the years subsequent to the 2009 pandemic. Methods: We studied two different periods of extracorporeal membrane oxygenation support for respiratory failure in children by analyzing datasets from the Extracorporeal Life Support Organization. Autoregressive integrated moving average models were constructed to estimate the effect of the pandemic. The year 2009 was the year of intervention (the H1N1 epidemic) in an interrupted time series model. Data collected from 2001 - 2010 were considered preintervention, and data collected from 2010 - 2017 were considered postintervention. Results: There was an increase in survival rates in the period 2010 - 2017 compared to 2001 - 2010 (p < 0.0001), with a significant improvement in survival when extracorporeal membrane oxygenation was performed for acute respiratory failure due to viral pneumonia. The autoregressive integrated moving average model shows an increase of 23 extracorporeal membrane oxygenation runs per year, prior to the point of the level effect (2009). In terms of survival, the preslope shows that there was no significant increase in survival rates before 2009 (p = 0.41), but the level effect was nearly significant after two years (p = 0.05), with a 6% increase in survival. In four years, there was an 8% (p = 0.03) increase in survival, and six years after 2009, there was up to a 10% (p = 0.026) increase in survival. Conclusion: In the years following 2009, there was a significant, global incremental increase in the extracorporeal membrane oxygenation survival rates for all runs, mainly due to improvements in the technology and treatment protocols for acute respiratory failure related to viral pneumonia and other respiratory conditions.
Validation of the QuEChERSER mega-method for the analysis of pesticides, veterinary drugs, and environmental contaminants in tilapia (Oreochromis Niloticus)

ABSTRACT Diverse food safety programmes around the world are designed to help ensure production of safe food. To meet this need, the development and implementation of more efficient and effective analytical methods to monitor residues (pesticides and veterinary drugs) and contaminants in food is important. In this study, we report the validation results for a simple high-throughput mega-method for residual analysis of 213 pesticides and veterinary drugs, including 15 metabolites, plus 12 environmental contaminants (polychlorinated biphenyls) in tilapia muscle for implementation in routine laboratory analyses. The generic sample preparation method and analytical approach are known as QuEChERSER (more than QuEChERS). A small portion of the initial extract (204 µL) is taken for analysis by ultrahigh-performance liquid chromatography (UHPLC) tandem mass spectrometry (MS/MS) covering 145 analytes, and the remaining extract undergoes a salting out step followed by an automated robotic instrument top sample preparation (ITSP) cleanup, also known as micro-solid-phase extraction (µSPE), plus fast low-pressure gas chromatography LPGC-MS/MS for 134 analytes (66 pesticides are targeted in both UHPLC-MS/MS and LPGC-MS/MS). The mega-method was validated in spiked tilapia samples at 5, 10, 15, and 20 ng/g with 10 replicates per level over two days (n = 80 overall), and 70–140% recoveries with RSDs ≤20% were achieved for 92% of the analytes in LC and 82% in GC. No significant matrix effects were observed for the analytes in LPGC-MS/MS, and only 5% of the analytes exceeded ±20% matrix effect in UHPLC-MS/MS. Analysis of standard reference materials (NIST SRMs 1946 and 1947) for contaminants in freeze-dried fish showed acceptable results, further demonstrating that the QuEChERSER mega-method can be implemented to expand analytical scope and increase laboratory efficiency compared to the QuEChERS method. Graphical abstract
Loss of miR-31-5p drives hematopoietic stem cell malignant transformation and restoration eliminates leukemia stem cells in mice

Leukemia stem cells (LSCs) propagate leukemia and are responsible for the high frequency of relapse of treated patients. The ability to target LSCs remains elusive, indicating a need to understand the underlying mechanism of LSC formation. Here, we report that miR-31-5p is reduced or undetectable in human LSCs compared to hematopoietic stem progenitor cells (HSPCs). Inhibition of miR-31-5p in HSPCs promotes the expression of its target gene FIH, encoding FIH [factor inhibiting hypoxia-inducing factor 1α (HIF-1α)], to suppress HIF-1α signaling. Increased FIH resulted in a switch from glycolysis to oxidative phosphorylation (OXPHOS) as the predominant mode of energy metabolism and increased the abundance of the oncometabolite fumarate. Increased fumarate promoted the conversion of HSPCs to LSCs and initiated myeloid leukemia-like disease in NOD-Prkdcscid IL2rgtm1/Bcgen (B-NDG) mice. We further demonstrated that miR-31-5p inhibited long- and short-term hematopoietic stem cells with a high frequency of LSCs. In combination with the chemotherapeutic agent Ara-C (cytosine arabinoside), restoration of miR-31-5p using G7 poly (amidoamine) nanosized dendriplex encapsulating miR-31-5p eliminated LSCs and inhibited acute myeloid leukemia (AML) progression in patient-derived xenograft mouse models. These results demonstrated a mechanism of HSC malignant transformation through altered energy metabolism and provided a potential therapeutic strategy to treat patients with AML. Description The microRNA miR-31-5p maintains glycolytic metabolism in hematopoietic stem cells to prevent development of leukemia. Targeting transformation Leukemia stem cells (LSCs) originate from hematopoietic stem cells (HSCs), but our understanding of this transformation is limited. Here, Zhu and colleagues identified the microRNA miR-31-5p as a controller of the mode of energy metabolism in HSCs: Loss of miR-31-5p led to a transition away from glycolytic metabolism to oxidative phosphorylation, accumulation of the oncometabolite fumarate, and development of LSCs, whereas ectopic expression of miR-31-5p could eliminate LSCs. Treatment with encapsulated miR-31-5p and cytosine arabinoside inhibited progression of disease and improved survival in mice-bearing patient-derived acute myeloid leukemia, suggesting that miR-31-5p may hold promise as a treatment for leukemias in humans.
Correlation between syndecan-1 level and PELOD-2 score and mortality in pediatric sepsis

Objective: To analyze the correlation between glycocalyx disruption measured via the serum syndecan-1 level and organ dysfunctions assessed by the PELOD-2 score and to evaluate its association with mortality in pediatric sepsis. Methods: We performed a prospective observational study in a tertiary public hospital. Sixty-eight pediatric patients diagnosed with sepsis according to International Pediatric Sepsis Consensus Conference criteria were consecutively recruited. We performed measurements of day 1 and day 5 serum syndecan-1 levels and PELOD-2 score components. Patients were followed up to 28 days following sepsis diagnosis. Results: Overall, the syndecan-1 level was increased in all subjects, with a significantly higher level among septic shock patients (p = 0.01). The day 1 syndecan-1 level was positively correlated with the day 1 PELOD-2 score with a correlation coefficient of 0.35 (p = 0.003). Changes in syndecan-1 were positively correlated with changes in the PELOD-2 score, with a correlation coefficient of 0.499 (p < 0.001) during the first five days. Using the cutoff point of day 1 syndecan-1 ≥ 430ng/mL, organ dysfunction (PELOD-2 score of ≥ 8) could be predicted with an AUC of 74.3%, sensitivity of 78.6%, and specificity of 68.5% (p = 0.001). Conclusion: The day 1 syndecan-1 level was correlated with the day 1 PELOD-2 score but not 28-day mortality. Organ dysfunction (PELOD-2 ≥ 8) could be predicted by the syndecan-1 level in the first 24 hours of sepsis, suggesting its significant pathophysiological involvement in sepsis-associated organ dysfunction.
Three‐variate trajectories of metabolic control, body mass index, and insulin dose: Heterogeneous response to initiation of pump therapy in youth with type 1 diabetes

Continuous subcutaneous insulin infusion (CSII) in youths with type 1 diabetes (T1D) is often associated with lower HbA1c, lower total daily insulin dose (TDD), and lower body mass index (BMI) compared with multiple daily injections (MDI). Individual responses to CSII are diverse. The aim was to identify unique three‐variate patterns of HbA1c, BMI standard deviation score (SDS), and TDD after switching to CSII.
A Prospective Study Using Propensity Score Matching to Compare Long-term Survival Outcomes After Robotic-assisted, Laparoscopic, or Open Liver Resection for Patients With BCLC Stage 0-A Hepatocellular Carcinoma

Objective: To compare the short- and long-term outcomes of robot-assisted (RALR), laparoscopic (LLR), or open liver resection (OLR) in the treatment of Barcelona Clinic Liver Cancer (BCLC) stage 0-A hepatocellular carcinoma (HCC). Summary Background Data: Following the Balliol IDEAL classification, long-term oncological outcomes can be used to evaluate the value of minimally invasive techniques in the treatment of HCC, and to assess whether they should become a standard practice. Methods: Data from prospective cohorts of patients with BCLC stage 0-A HCC who underwent curative liver resection using OLR, LLR, or RALR at Tongji Hospital were reviewed. The short-term and long-term oncological outcomes of these 3 different surgical approaches after adequate follow-up were compared using propensity score matching to reduce selection bias. Results: Of 369 patients included in this study (71, RALR; 141, LLR; and 157, OLR), 56 patients in each of the 3 groups were chosen for further comparison, after propensity score matching. In the minimally invasive group (RALR+LLR), both the operative time and duration of Pringle’s maneuver were significantly longer than those in the OLR group; however, the length of hospital stay was significantly shorter. There were no significant differences in the other intraoperative parameters and the incidence of postoperative complications among the 3 groups. HCC recurrence in the minimally invasive group when compared with the OLR group was characterized by a significantly higher proportion of single lesion or early-stage HCC. However, there were no significant differences in the 5-year disease-free survival (63.8%, 54.4%, and 50.6%) or overall survival rates (80.8%, 78.6%, and 75.7%, respectively) among the 3 groups. Clinically significant portal hypertension was the only risk factor that negatively affected the 5-year disease-free survival rate. Multivariate Cox regression analysis showed that clinically significant portal hypertension, serum alpha-fetoprotein level (≥400 ng/mL), and Edmondson-Steiner grading (III+IV) were independent risk factors for poor long-term survival. Conclusion: Both robotic and laparoscopic hepatectomies were safe and effective for patients with BCLC stage 0-A HCC when compared with open hepatectomy.
An eye-tracking investigation of the cognitive processes involved in the comprehension of simple and complex communicative acts

Indirect speech acts communicate more than their literal meaning, and their comprehension relies on the listener’s ability to draw the appropriate inferences in a given context. We used eye tracking to investigate the cognitive processing involved in the comprehension of simple (direct) and complex (unconventional indirect) communicative acts, a more general distinction that applies not only to sincere speech acts, but also to irony and deceit. We recorded the eye movements of 40 participants while they read 60 stories (20 sincere, 20 deceitful, 20 ironic) consisting of a context and a target answer. For each story, we created two different contexts so that the same identical target answer was a simple (direct) and a complex (unconventional indirect) communicative act, respectively. We also assessed the indirectness of simple and complex communicative acts, as well as participants’ working memory (WM) and theory of mind (ToM). Eye-pattern analysis showed that complex communicative acts were more difficult to understand than simple acts; differences between simple and complex acts held for all the pragmatic phenomena investigated, though processing differences were greater for sincere acts than for irony and deceit. We found a role of indirectness and ToM in the pragmatic processing of simple and complex acts, whereas the role of WM was modest. The present findings underscore the importance of adopting an encompassing theory that can account for different types of indirect speech acts, such as sincere, deceitful and ironic acts; they also suggest the importance of assessing individual differences in inferential and cognitive abilities.
Monitoring and adapting cancer treatment using circulating tumor DNA kinetics: Current research, opportunities, and challenges

Circulating tumor DNA (ctDNA) has emerged as a biomarker with wide-ranging applications in cancer management. While its role in guiding precision medicine in certain tumors via noninvasive detection of susceptibility and resistance alterations is now well established, recent evidence has pointed to more generalizable use in treatment monitoring. Quantitative changes in ctDNA levels over time (i.e., ctDNA kinetics) have shown potential as an early indicator of therapeutic efficacy and could enable treatment adaptation. However, ctDNA kinetics are complex and heterogeneous, affected by tumor biology, host physiology, and treatment factors. This review outlines the current preclinical and clinical knowledge of ctDNA kinetics in cancer and how early on-treatment changes in ctDNA levels could be applied in clinical research to collect evidence to support implementation in daily practice.