Miracle-dz/UniFAR-FTUs huggingface dataset:
Durvalumab after concurrent chemotherapy and high-dose radiotherapy for locally advanced non-small cell lung cancer

ABSTRACT The standard of care for stage III non-small cell lung cancer (NSCLC) is chemoradiotherapy (CRT) followed by durvalumab. Although doses higher than 66 Gy are standard in our center, they were used in only 6.9% of patients in the PACIFIC trial. We report our experience with durvalumab after high-dose radiotherapy. The database of a tertiary hospital for patients with stage III NSCLC who were treated with CRT and adjuvant durvalumab was evaluated. Progression-free survival (PFS), overall survival (OS), and local-regional failure (LRF) were measured from the administration of durvalumab. Thirty-nine patients were included. All were treated with intensity-modulated radiation (mean dose 69.9 Gy); Median follow-up time was 20.4 months (range 1–35.4). At 12 months, PFS was 49%, OS 79%, and LRF 14%. Intrathoracic failure at first progression was demonstrated in 8 (21%) patients. Adverse events requiring corticosteroids occurred in 10(25.6%) patients: pneumonitis – 6 (15.4%), hepatitis – 2 (5.1%), and arthralgia and pericarditis – 1 (2.6%). One patient (2.6%) died of pneumonitis. The occurrence of pneumonitis was significantly associated with lung V5 (55% vs. 42%, p = .04) and V20 (28% vs. 19%, p = .01) and mean lung dose (14.8 Gy vs.11.6 Gy, p = .05). The similar 12-month PFS and OS rates of our cohort and the PACIFIC trial support the use of high-dose radiotherapy in patients with stage III NSCLC. Treatment-related mortality was similar to the PACIFIC results. The intrathoracic failure rate in our cohort was lower than that reported from the PACIFIC trial, suggesting that radiation dose escalation may improve local control.
Factors associated to quality of life in patients with leprosy

ABSTRACT Objective To evaluate quality of life and associated factors in patients with leprosy. Methods A cross-sectional study with 63 people diagnosed as leprosy, seen at a reference service for the disease in the southeastern region of Mato Grosso, Brazil. The questionnaire World Health Organization Quality of Life Bref was used to evaluate quality of life. Simple and multiple linear regressions evaluated the association between sociodemographic variables and quality of life domains. Results The highest mean of quality of life was observed in the psychological domain (16.28±2.30), and the lowest in the environmental domain (13.86±2.21). Females, individuals with no partners, and people who owned their own house had the lowest quality of life means within the psychological domain. People who did not receive visits by Community Health Workers had the lowest means in quality of life within the environmental domain. Multivariate analysis revealed that the best quality of life was associated to self-reported white skin color within the environmental domain, and the worst quality of life was associated to less schooling within the physical domain. Conclusion This study showed the influence of sociodemographic factors on the quality of life of patients with leprosy, and indicated the need for comprehensive health care, considering the social determinants of health.
Factors Affecting Pre-Hospital and In-Hospital Delays in Treatment of Ischemic Stroke; a Prospective Cohort Study

Introducion: The outcomes of acute ischemic stroke (AIS) are highly affected by time-to-treatment. The present study aimed to determine the factors affecting in-hospital and pre-hospital delays in treatmentof AIS. Methods: This prospective study was carried out on 204 AIS patients referring to the stroke care unit in Zanjan (Iran) in 2019. The required data were collected by interviewing the patients and families and using patients’ records and observations. Results: The maximum delay was related to onset-to-arrival time (288.19 ± 339.02 minutes). The logistic regression analysis indicated a statistically significant decline in the treatment delay via consultation after the initiation of symptoms (p< 0.001), transferring the patient through emergency medical service to the hospital (p<0.001), and patients’ perception regarding AIS symptoms (P< 0.001). Conclusion: It is essential to inform people regarding AIS symptoms and referring to AIS treatment units to reduce the treatment time.
Stabilizing the Ordered Bicontinuous Double Diamond Structure of Diblock Copolymer by Configurational Regularity

We investigate the formation of the ordered bicontinuous structures in a stereoregular diblock copolymer, isotactic polypropylene-block-polystyrene (iPP-b-PS), in which the minority PP block possessed isotactic configuration. This diblock displayed the conventional ordered bicontinuous double gyroid (OBDG) morphology upon heating above the crystal melting point of the iPP block from the as-cast state. The OBDG phase remained stable in the heating process up to the order–disorder transition. In the subsequent cooling process from the nearly disordered state, the OBDG phase first developed, but when the temperature was sufficiently low, an order–order transition from OBDG to the ordered bicontinuous double diamond (OBDD) phase occurred, and OBDD eventually became the dominant structure. The results attested that OBDD and OBDG represented the thermodynamically stable structure at the lower and the higher temperature, respectively, and the OBDG morphology formed in the as-cast state was metastable. The presen.
No difference in biomarkers of ischemic heart injury and heart failure in patients with COVID-19 who received treatment with chloroquine phosphate and those who did not

Background Chloroquine was promoted as a COVID-19 therapeutic early in the pandemic. Most countries have since discontinued the use of chloroquine due to lack of evidence of any benefit and the risk of severe adverse events. The primary aim of this study was to examine if administering chloroquine during COVID-19 imposed an increased risk of ischemic heart injury or heart failure. Methods Medical records, laboratory findings, and electrocardiograms of patients with COVID-19 who were treated with 500 mg chloroquine phosphate daily and controls not treated with chloroquine were reviewed retrospectively. Controls were matched in age and severity of disease. Results We included 20 patients receiving chloroquine (500 mg twice daily) for an average of five days, and 40 controls. The groups were comparable regarding demographics and biochemical analyses including C-reactive protein, thrombocytes, and creatinine. There were no statistically significant differences in cardiac biomarkers or in electrocardiograms. Median troponin T was 10,8 ng/L in the study group and 17.9 ng/L in the control group, whereas median NT-proBNP was 399 ng/L in patients receiving chloroquine and 349 ng/L in the controls. Conclusions We found no increased risk of ischemic heart injury or heart failure as a result of administering chloroquine. However, the use of chloroquine to treat COVID-19 outside of clinical trials is not recommended, considering the lack of evidence of its effectiveness, as well as the elevated risk of fatal arrythmias.
The influence of childhood adversities on mid to late cognitive function: From the perspective of life course

Background The effects of childhood adversities on cognitive function in later life are well reported. However, few studies have examined the cumulative mechanism, especially in Chinese population. This study aims to explore this cumulative effects of childhood adversities on mid to late cognitive decline in China. Methods Data were drawn from the second and third wave of the China Health and Retirement Longitudinal Study (CHARLS). We included 9,942 respondents aged 45 and above and retrospectively collected information on childhood adversities. Cognitive function was measured in three dimensions: orientation and calculation, immediate memory, and delayed memory. A structural equation model was employed for analysis. Results Age (β = -0.155, P<0.001) and mid to late depressive symptoms (β = -0.041, P<0.001) showed direct effects on cognitive decline. Low mid to late life socioeconomic status (SES) showed a direct effect on mid-late cognitive impairment (β = 0.603, P<0.001) and an indirect effect through depression (β = 0.007, P<0.001). Low childhood SES (β = 0.310, P<0.001), lack of friends (β = 0.208, P<0.001), parental mental health problems (β = 0.008, P<0.001), and poor relationship with parents (β = 0.001, P<0.001) had an indirect effect on cognitive impairment. Conclusions Childhood adversities had negative effects on cognitive function among middle aged and elderly population in China. The findings suggest that early counter measures on childhood adversities may lead to an effective reduction of cognitive impairment.
Therapeutic Effect of Murine Bone Marrow-Derived Mesenchymal Stromal/Stem Cells and Human Placental Extract on Testicular Toxicity Resulting from Doxorubicin in Rats

Oncotherapeutics like doxorubicin can affect male gonads; as a result, it leads to infertility. This work was conducted to demonstrate the toxic effects of doxorubicin on testes of male albino rats. Fifty male albino rats aged 5-7 weeks were used in this study. The animals were randomly separated into 5 sets (each set containing ten rats). Group I received saline (i.p.) for 4 weeks. Group II was given doxorubicin (DOX), 5 mg/kg BW (i.p.) once/week for 4 weeks. Groups III and IV were treated in the same way as the DOX group, left for one week without medication, and then injected with mesenchymal stromal cells (MSCs) or human placental extract (HPE) therapy in a single dose of 5 × 106 in 200 ml PRP/week or 40 μl placental extract for 4 weeks via the caudal vein. Group V rats were treated in the same way as the DOX group also, left for one week without medication, and then injected with MSC+HPE. A significant decrease in serum testosterone, FSH, and LH levels was observed in rats treated with DOX compared to the control group. A significant elevation was recorded in rats treated with DOX+MSC or DOX+HPE when compared with the DOX group only. Rats that were given MSC+HPE after DOX intoxication showed a significant increase in hormone levels when compared to rats treated with either MSC or HPE. Light and electron microscopic examinations revealed that DOX intoxication initiated degenerative and necrotic changes in seminiferous tubules associated with partial or complete cessation of spermatogenesis. These effects were reversed by the effect of MSC or HPE. Coadministration of MSC and HPE even showed further improvement. Finally, we can say that doxorubicin has a deleterious impact on rat testes; however, therapeutic effects can be induced through MSC and/or HPE administration.
Evaluation of the blood-oxygen-level-dependent (BOLD) sequence with 3 Tesla device in renal transplant patients in the assessment of early allograft disfunction, correlated with biopsy

ABSTRACT Objective To evaluate the ability of blood-oxygen-level-dependent (BOLD) magnetic resonance imaging at 3 Tesla to measure tissue oxygen bioavailability based on R2* values, and to differentiate between acute tubular necrosis and acute rejection compared to renal biopsy (gold standard). Methods A prospective, single-center study, with patients submitted to renal transplantation between 2013 and 2014, who developed graft dysfunction less than 4 weeks after transplantation. All patients were submitted to abdominal magnetic resonance imaging at 3 Tesla using the same protocol, followed by two BOLD sequences and kidney biopsy. Results Twelve male (68.75%) and three female (31.25%) patients were included. A total of 19 percutaneous renal biopsies were performed (four patients required a second biopsy due to changes in clinical findings). Pathological findings revealed ten cases of acute tubular necrosis, four cases of acute rejection, and five cases with other (miscellaneous) diagnoses. Comparison between the four groups of interest failed to reveal significant differences (p=0.177) in cortical R2* values, whereas medullary R2* values differed significantly (p=0.033), with lower values in the miscellaneous diagnoses and the acute tubular necrosis group. Conclusion BOLD magnetic resonance imaging at 3 Tesla is a feasible technique that uses indirect tissue oxygen level measurements to differentiate between acute rejection and acute tubular necrosis in renal grafts.
Diagnosis and prognostic value of C-X-C motif chemokine ligand 1 in colon adenocarcinoma based on The Cancer Genome Atlas and Guangxi cohort

Objective: The objective was to identify and validate C-X-C motif chemokine ligand 1(CXCL1) for diagnosis and prognosis in colon adenocarcinoma (COAD). Methods: Our current study had enrolled one The Cancer Genome Atlas (TCGA) cohort and two Guangxi cohorts to identify and verify the diagnostic and prognostic values of CXCL1 in COAD. Functional enrichment was performed by gene set enrichment analysis (GSEA). Results: In TCGA cohort, the expression of CXCL1 was significantly up-regulated in tumor tissues and decreased as the tumor stage developed. The receiver operating characteristic (ROC) curve showed that CXCL1 had a high diagnostic value for COAD. The result of Kaplan-Meier survival analysis showed that CXCL1 gene expression (P=0.045) was significantly correlated with overall survival (OS) of COAD. Results of Guangxi cohort also verified the diagnostic value of CXCL1 in COAD, and sub-group survival analyses also suggested that patients with high CXCL1 expression were related to a favorable OS (Corrected P=0.005). GSEA revealed that CXCL1 high expression phenotype was related to cytokine activity, cell apoptosis, P53 regulation pathway, and regulation of autophagy in COAD. Conclusions: In this study, we found that CXCL1 gene might be a potential diagnostic biomarker for COAD, and might serve as a prognostic biomarker for specific subgroup of COAD.
The complete chloroplast genome of Petunia exserta (Solanaceae: Petunioideae), an endangered ornamental species

Abstract Petunia exserta is an ornamental species on the brink of extinction in the wild. We report here the complete chloroplast genome of P. exserta, which is 156,598 bp in size consisting of a large single-copy region (87,095 bp), a small single-copy region (18,643 bp), and a pair of inverted repeats (25,430 bp for each). The chloroplast (used ‘cp’ hereafter) genome contains 132 genes, including 8 rRNA genes, 37 tRNA genes, and 87 protein-coding genes. Phylogenetic analysis demonstrated that P. exserta was most closely related to P. hybrida, and they together were closer to Calibrachoa hybrida than other taxa in the Solanaceae family.
Antioxidant properties of flavonoid derivatives and their hepatoprotective effects on CCl4 induced acute liver injury in mice

Excessive accumulation of free radicals in the body can cause liver damage, aging, cancer, stroke, and myocardial infarction. Anastatin B, a skeletal flavonoid, was reported to have antioxidant and hepatoprotective effects. Anastatin B derivatives, compound 1 and 2, were synthesized by our group previously. In this study, their antioxidant activity and hepatoprotective mechanism were studied using chemical evaluation methods, a cellular model of hydrogen peroxide (H2O2)-induced oxidative damage, and a mouse model of carbon tetrachloride (CCl4)-induced liver injury. Results from the chemical evaluation suggested that both compounds had good antioxidant power and radical scavenging ability in vitro. MTT assay showed that both compounds had cytoprotective activity in H2O2-treated PC12 cells. Moreover, their hepatoprotective activities evaluated using a mouse model of CCl4-induced liver injury that compared with the model group, pretreatment with compound 1 and 2 significantly decreased alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), and malondialdehyde (MDA) levels; reduced the liver tissue damage; and increased glutathione content. However, compound 2 was a more effective hepatoprotectant than compound 1 was. Finally, the amount of TNF-α and cytochrome P450 2E1 (CYP2E1) were significantly downregulated in compound 1 and 2 pretreatment groups. Collectively, our findings demonstrate that both compounds have potential antioxidant activity and hepatoprotective effect in vitro and in vivo. Further chemo-biological study and investigation of the compounds' enzymatic targets are ongoing.
Immune checkpoints and the multiple faces of B cells in systemic lupus erythematosus

Purpose of review B-lymphocytes are crucial in the pathogenesis of systemic lupus erythematosus (SLE), including autoantibody production, antigen presentation, co-stimulation, and cytokine secretion. Co-stimulatory and co-inhibitory molecules control interactions between B and T cells during an inflammatory response, which is essential for an appropriate host protection and maintenance of self-tolerance. Here, we review recent findings about checkpoint molecules and SLE B cells including their potential therapeutic implications and experiences from clinical trials. Recent findings Most prominent checkpoint molecules involved in pathologic B and T cell interaction in SLE are CD40/CD40L and inducible co-stimulator/ICOSL, both also intimately involved in the formation of germinal centers and ectopic lymphoid tissue. Dysregulations of inhibitory checkpoint molecules, like programmed death-1/programmed death-ligand 1 and B- and T-lymphocyte attenuator have been suggested to impair B cell functions in SLE recently. Summary Accumulating evidence indicates that dampening immune responses by either blocking co-activating signals or enhancing co-inhibitory signals in different cell types is a promising approach to treat autoimmune diseases to better control active disease but may also allow resolution of chronic autoimmunity.
Association between sports participation history and age of first exposure to high-risk sports with concussion history

ABSTRACT The purpose of this study was to examine the association between sports participation history, including estimated age of first exposure (eAFE) to high-risk sports, and concussion history in first year (i.e., freshmen) collegiate athletes. Athletes increased their odds of sustaining a pre-college concussion by 5% [odds ratio(OR) = 1.05 (95%CI:1.05–1.06)] for each additional year of contact sports participation – 24% of all student athletes reported one or more pre-college concussions. When eAFE was analysed dichotomously at age 12, a greater proportion of those who started playing football before age 12 reported a positive concussion history compared to those who started playing football at age 12 or later (Х2 = 4.483, p = 0.034, Phi = 0.049). When eAFE was analysed continuously, later eAFE to women’s high-risk sports was associated with a lower likelihood of sustaining a pre-college concussion [OR = 0.93 (95%CI:0.88–0.98)]. Our findings suggest that there is a relationship between eAFE to football and to women’s high-risk sports and concussion history.
Early Neurologic Deterioration in Lacunar Stroke

Background and Objectives To determine the rate and predictors of early neurologic deterioration (END) in patients with lacunar strokes and its implications for management and outcome. Methods We enrolled consecutive patients with MRI-defined lacunar stroke who presented within 12 hours after symptom onset from a prospective stroke database (2015–2019). END was defined as any persisting increase in NIH Stroke Scale (NIHSS) score of ≥2 points within 24 hours after admission and favorable outcome as modified Rankin Scale (mRS) score of 0 to 2 at 90 days. We assessed the association of END with clinical and imaging variables, acute treatment, and outcome using multivariable regression, calculating adjusted odds ratios (aORs). Results Sixty-one of 365 (16.7%) patients with acute lacunar stroke (median age 71.8 years, 39.5% female, median NIHSS score on admission 3) had END. Lower NIHSS score on admission (per point, aOR 0.81, p = 0.006), capsular warning syndrome (aOR 7.00, p < 0.001), ventral pontine infarct (aOR 3.49, p = 0.008), and hypoperfusion lesion on imaging (aOR 2.13, p = 0.026) were associated with END. Acute dual antiplatelet therapy was associated with reduced risk of END (aOR 0.10, p = 0.04). Patients with END had less favorable outcome at 90 days (aOR 0.13 p < 0.001), but IV thrombolysis (IVT) was associated with favorable outcome at 90 days (aOR 3.95, p = 0.002). Discussion One in 6 patients with lacunar stroke has END, and patients at high risk of END can be identified with radiologic and clinical variables. Targeted therapeutic trials for this population seem justified. Classification of Evidence This study provides Class II evidence that early neurologic deterioration in patients with acute lacunar stroke predicts poorer functional outcome at 90 days as determined by the mRS.
The influence of inter-dialect contact on the Korean three-way laryngeal distinction: An acoustic comparison among Seoul Korean speakers and Gyeongsang speakers with limited and extended residence in Seoul

This exploratory study investigates the acoustic correlates of the Korean three-way laryngeal stop distinction in Gyeongsang long-term (LT) transplants who were born in the Gyeongsang region but moved to Seoul to pursue higher education. Acoustic data were collected from eight LT transplants, five short-term (ST) transplants, and 11 Seoul speakers to examine whether exposure to Seoul Korean (SK) affects Gyeongsang speakers’ cue-weighting in distinguishing stops in production. LT transplants produced stimuli in both Gyeongsang and Seoul dialects. A cue-weighting model based on the acoustic data reveals that voice onset time (VOT) is less important to distinguish lenis from aspirated stops for Seoul speakers and for LT transplants’ SK, as compared to ST transplants and LT transplants’ Gyeongsang Korean (GK). In addition, fundamental frequency (F0) is more important for the lenis–aspirated distinction for Seoul speakers and LT transplants’ SK, as compared to ST and LT transplants’ GK, showing that LT transplants rely less on VOT and more on F0 to distinguish lenis from aspirated stops compared to ST transplants. LT transplants’ SK reveals that they rely more on VOT and less on F0 compared to SK speakers. The cue-weighting model of the LT transplants provide empirical evidence that a series of sound changes in GK is due to inter-dialect contact.
Evaluating filgotinib for the treatment of rheumatoid arthritis

ABSTRACT Introduction Despite the availability of an extensive armamentarium, rheumatoid arthritis (RA) remains a therapeutic challenge for rheumatologists. Janus kinase inhibitors (JAKi) are an emerging class of targeted therapies. The number of JAKi has been growing and to date, filgotinib is the latest JAKi to be approved for use in RA. Areas covered This review focuses on the pharmacodynamics, pharmacokinetics, efficacy and safety of filgotinib in patients with RA. Expert opinion Filgotinib is an oral targeted synthetic disease-modifying antirheumatic drug (DMARD) that specifically inhibits JAKi. Filgotinib monotherapy, or a combination regimen with conventional synthetic (cs) DMARDs, has demonstrated efficacy in decreasing disease activity, with a well-managed safety profile in patients with early RA naive to DMARDs, and in RA that does not adequately respond to csDMARDs and/or biologic DMARDs. The selective inhibition of JAK1 may confer an improved safety profile, but further study is required as a potential testicular toxicity has been suggested. Filgotinib offers several advantages: oral administration, rapidity of action, efficacy as monotherapy, and demonstrated activity in difficult to treat RA. However, the placement of filgotinib in the therapeutic arsenal for RA may be influenced by the ongoing collection of long-term safety data from JAKi as a class.