Miracle-dz/UniFAR-FTUs huggingface dataset:
Interferon-α Is Effective for Treatment of Minimal Residual Disease in Patients with t(8;21) Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation: Results of a Prospective Registry Study.

BACKGROUND RUNX1-RUNX1T1 transcript levels were established as a powerful marker for predicting relapse in patients with t(8;21) acute myeloid leukemia (AML). We aimed to identify the efficacy of minimal residual disease (MRD)-directed interferon-alpha (IFN-α) treatment in patients with t(8;21) AML who were positive for MRD after allogeneic hematopoietic stem cell transplantation (allo-HSCT; n=42). SUBJECTS, MATERIALS, AND METHODS MRD-positive status was defined as a <4.5-log reduction from diagnosis in RUNX1-RUNX1T1 transcripts and/or the loss of a ≥4.5-log reduction after 3 months after HSCT. Patients with positive MRD received six cycles of IFN-α treatment (twice or thrice weekly of every 4 weeks cycle). RESULTS The 1-year cumulative incidence of severe acute and chronic graft-versus-host disease after MRD-directed IFN-α treatment was 7.1% and 4.8%, respectively. After the treatment, 15 (35.7%), 5 (11.9%), 3 (7.1%), and 9 (21.5%) patients achieved MRD negativity at 1, 2, 3, and >3 months, respectively. Three patients relapsed after the IFN-α treatment, in which the 1-year cumulative incidence of relapse was 7.2%. One patient died of severe infection at 460 days after treatment. The 1-year probabilities of event-free survival, disease-free survival, and overall survival after treatment were 76.0%, 92.4%, and 92.5%, respectively. The clinical outcomes in patients who received MRD-directed IFN-α treatment were significantly better than those of the MRD-positive patients without any interventions in the historical cohort. CONCLUSION MRD-directed IFN-α treatment is effective for patients with t(8;21) AML who were MRD-positive after allo-HSCT. The study was registered at http://clinicaltrials.gov as NCT02027064. IMPLICATIONS FOR PRACTICE In patients with t(8;21) acute myeloid leukemia (AML), the presence of post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) minimal residual disease (MRD), measured by RUNX1-RUNX1T1 transcript levels, has been established as a powerful marker for predicting relapse. Interferon-alpha (IFN-α) could exert a relatively strong graft-versus-leukemia effect, and MRD-directed IFN-α treatment is effective for patients with t(8;21) AML who were MRD-positive after allo-HSCT.
Incidence of gallstones after gastric resection for gastric cancer: a nationwide claims-based study

Purpose Gallstone formation is one of the most common problems after gastrectomy. This retrospective cohort study used the South Korean nationwide claims database to evaluate the incidence and risk factors of gallstone after gastrectomy for gastric cancer. Methods All consecutive patients who underwent gastrectomy for gastric cancer in South Korea in 2008–2010 were identified. Incidence of gallstone formation 5 years after gastrectomy in males and females, in various age groups, and after different types of gastrectomy was determined. Multivariate logistic regression analysis served to identify gallstone risk factors. Results Of the 47,752 patients, 2,506 (5.2%) developed gallstone during the 5-year follow-up period. At 12, 24, 36, and 48 months, the cumulative incidences were 1.2%, 2.2%, 3.3%, and 4.3%, respectively. Males had a higher incidence than females (5.8% vs. 4.1%, P < 0.001). Older patients (60–89 years) had a higher incidence than younger patients (30–59 years) (6.1% vs. 4.3%, P < 0.001). Gallstone was most common after total gastrectomy (6.6%), followed by proximal gastrectomy (5.4%), distal gastrectomy (4.8%), and pylorus-preserving distal gastrectomy (4.0%) (P < 0.001). Multivariate analysis showed that male sex (odds ratio [OR], 1.39), an older age (OR, 1.44), and total gastrectomy (OR, 1.40 vs. distal gastrectomy) were significant independent risk factors for postgastrectomy gallstone. Conclusion The cumulative incidence of gallstone 5 years after gastrectomy for gastric cancer was 5.2%. Male sex, an older age, and total gastrectomy were significant risk factors. More careful monitoring for gallstone may be necessary in patients with such risk factors.
Monitoring Blood Biomarkers and Training Load Throughout a Collegiate Soccer Season.

Huggins, RA, Fortunati, AR, Curtis, RM, Looney, DP, West, CA, Lee, EC, Fragala, MS, Hall, ML, and Casa, DJ. Monitoring blood biomarkers and training load throughout a collegiate soccer season. J Strength Cond Res XX(X): 000-000, 2018-This observational study aimed to characterize the responses of a comprehensive panel of biomarkers, observed ranges, training load (TL) metrics, and performance throughout the collegiate soccer season (August-November). Biomarkers (n = 92) were collected before the start of pre-season (PS), in-season weeks (W)1, W4, W8, and W12 in NCAA Division I male soccer players (n = 20, mean ± SD; age = 21 ± 1 years, height = 180 ± 6 cm, body mass = 78.19 ± 6.3 kg, body fat = 12.0 ± 2.6%, V[Combining Dot Above]O2max 51.5 ± 5.1 ml·kg·min). Fitness tests were measured at PS, and W12 and TL was monitored daily. Changes in biomarkers and performance were calculated via separate repeated-measures analysis of variance. Despite similar fitness (p > 0.05), endocrine, muscle, inflammatory, and immune markers changed over time (p < 0.05). Total and free testosterone was lower in W1 vs. PS, whereas free cortisol remained unchanged at PS, W1, and W4 (>0.94 mg·dL). Oxygen transport and iron metabolism markers remained unchanged except for HCT (W1 vs. PS) and total iron binding capacity (W8-W12 vs. W1). Hepatic markers albumin, globulin, albumin:globulin, and total protein levels were elevated (p < 0.05) at W12 vs. W1, whereas aspartate aminotransferase and alanine aminotransferase levels were elevated at W1-W12 and W8-W12 vs. PS, respectively. Vitamin E, zinc, selenium, and calcium levels were elevated (p < 0.05) at W12 vs. W1, whereas Vitamin D was decreased (p < 0.05). Fatty acids and cardiovascular markers (omega-3 index, cholesterol:high-density lipoprotein [HDL], docosahexenoic acid, low-density lipoprotein [LDL], direct LDL, non-HDL, ApoB) were reduced at W1 vs. PS (p ≤ 0.05). Immune, lipid, and muscle damage biomarkers were frequently outside clinical reference ranges. Routine biomarker monitoring revealed subclinical and clinical changes, suggesting soccer-specific reference ranges. Biomarker monitoring may augment positive adaptation and reduce injuries from stressors incurred during soccer.
Role of TNFRSF1A and TNFRSF1B polymorphisms in susceptibility, severity, and therapeutic efficacy of etanercept in human leukocyte antigen-B27-positive Chinese Han patients with ankylosing spondylitis

Abstract The successful therapeutic use of anti-TNF biological agents in patients with ankylosing spondylitis (AS) indicates that tumor necrosis factor-&agr; (TNF-&agr;) and tumor necrosis factor receptor (TNFR) genes are involved in the pathogenesis of AS. TNF-&agr; exerts its biological activity by binding to its cell surface receptors (p55 TNF-&agr; receptor [TNFRI, encoded by the Tumor Necrosis Factor Receptor Superfamily Member 1A (TNFRSF1A)] and p75 receptor [TNFRII, encoded by the Tumor Necrosis Factor Receptor Superfamily Member 1B (TNFRSF1B)]. TNFRSF1A and TNFRSF1B may be related to AS, but the relevant studies are still limited. Therefore, we aim to explore the association between TNFRSF1A and TNFRSF1B polymorphisms and susceptibility and short- and long-term response to anti-TNF treatment in human leukocyte antigen-B27 (HLA-B27)-positive Chinese Han patients with AS. A total of 215 HLA-B27-positive patients with AS and 216 HLA-B27-positive matched controls were enrolled and genotyped for rs767455, rs2234649, and rs1061622. A subset of 50 AS patients was also studied for the association of these polymorphisms with the short- and long-term response to etanercept assessed by Assessment in Ankylosing Spondylitis 20 (ASAS20) and Assessment in Ankylosing Spondylitis 40 (ASAS40). Our data showed that rs767455 was associated with the susceptibility of AS, G allele of rs767455 exhibited an association with the risk of developing AS (OR = 1.63 (1.04–2.55), P = . 032). Rs1061622 polymorphism was associated with total back pain and chest expansion. Only rs1061622 was significantly associated with long-term efficacy of etanercept: the TG genotype of rs1061622 worsened ASAS20 and ASAS40 responses at 12 months (P = .021 and .041, respectively). The results suggest that TNFRSF1A and TNFRSF1B polymorphisms were associated with susceptibility, severity, and the long-term therapeutic efficacy of etanercept of patients with AS.
3-Factor Versus 4-Factor PCC in Coagulopathy of Trauma: Four is Better Than Three.

INTRODUCTION Coagulopathy of trauma (COT) is common and highly lethal. Prothrombin complex concentrate (PCC) has been advocated for correction of COT. However, the difference in efficacy between three-factor PCC (3-PCC) versus four-factor PCC (4-PCC) remains unclear. The aim of our study was to compare efficacy of 3-PCC versus 4-PCC in COT. METHODS Five-year (2013-2017) review of coagulopathic trauma patients at our Level-I trauma center who received 3- or 4-PCC. Patients were divided into two groups (4-PCC and 3-PCC) and matched in 1:1 ratio using propensity-score-matching for demographics, injury parameters, admission vitals, and hematological parameters. Primary outcomes were time to correction of international normalized ratio (INR), blood products transfusion, thromboembolic complications, and mortality. Secondary outcomes were hospital-length of stay (LOS), intensive care unit (ICU)-LOS, cost of therapy, and total hospital cost. RESULTS Six hundred fifty-seven patients met inclusion criteria of whom 250 patients (4-PCC:125; 3-PCC:125) were matched. The mean age was 50 ± 19.4 y, 64% were male, and median-injury severity score was 24[15-33]. 4-PCC was associated with accelerated correction of INR (365 vs. 428 min, P = 0.01), decrease in red blood cells (7 units vs. 10 units, P = 0.04) and FFP (6 units vs. 8 units, P = 0.03) transfused. There was no difference in platelet transfusion, thromboembolic complications, mortality, hospital, and ICU-LOS. 4-PCC was associated with higher cost of PCC therapy, and lower cost of transfusion. There was no difference regarding the total hospital cost between the two groups. CONCLUSION Compared with 3-factor PCC, the use of 4-factor PCC is associated with a rapid reversal of INR and reduction in transfusion requirement without increasing the overall hospital cost or the risk of thromboembolic events. 4-PCC may be preferred as an adjunct for the resuscitation of coagulopathic trauma patients.
Necitumumab in the treatment of non-small-cell lung cancer: clinical controversies

ABSTRACT Introduction: Over the last decade, epidermal growth factor receptor (EGFR) signaling was investigated as a potential target for tyrosine kinase inhibitors in the treatment of non-small-cell lung cancer (NSCLC). Necitumumab is a fully humanized IgG1 monoclonal antibody directed against the binding domain of EGFR, approved in combination with cisplatin–gemcitabine for the first-line treatment of squamous NSCLC. Areas covered: The purpose of this manuscript is to systematically review the state of the art of necitumumab for the treatment of metastatic NSCLC, focusing on predictive factors, cost-effectiveness, and future potential combinations with additional agents. Expert opinion: Despite recent therapeutic advances, platinum-based chemotherapy still represents the most widely used first-line treatment for advanced NSCLC, particularly for the squamous histotype. Necitumumab is nowadays the first targeted agent providing an (statistically significant) additional survival gain to squamous NSCLC patients when combined with first-line chemotherapy at the cost of an increased (although manageable) toxicity, as shown in the SQUIRE trial. Hopefully, improvement in patients’ selection by identifying reliable predictive markers and the combination with new agents may help to maximize the benefit of this targeted treatment, which is currently limited by a not optimal cost–benefit ratio.
MFG‐E8/integrin β3 signaling contributes to airway inflammation response and airway remodeling in an ovalbumin‐induced murine model of asthma

Asthma is the most common chronic childhood disease worldwide, characterized by airway remodeling and chronic inflammation, orchestrated primarily by Th2 cytokines. The aim of the current study was to explore the influences of milk fat globule epidermal growth factor 8 (MFG‐E8)/integrin β3 signaling involved in airway inflammation and remodeling in asthma. BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA), followed by OVA nebulization. The levels of MFG‐E8 expression were declined markedly in the OVA‐induced allergy murine model. In addition, administration of MFG‐E8 strongly reduced the accumulation of T‐helper type 2 (Th2)‐associated cytokines (such as interleukin‐4, ‐5, and ‐13) as well as chemokine CCL11 (eotaxin) in bronchoalveolar lavage fluid and tissues in the OVA‐sensitized mice. Moreover, MFG‐E8 remarkably repressed the total immunoglobulin E and OVA‐specific immunoglobulin E in serum in OVA‐challenged mice. Meanwhile, treatment with recombinant murine MFG‐E8 noticeably prevented inflammatory cell infiltration into the airways, as showed by a marked decrease in the numbers of total immune cells, eosinophils, neutrophils, macrophages, and lymphocytes in the bronchoalveolar lavage fluid in response to OVA challenge. Importantly, MFG‐E8 apparently alleviated OVA‐driven airway remodeling, which were evidenced by declined secretion of important mediators of airway remodeling, including transforming growth factor‐β1, matrix metalloproteinase 9, ADAM8, and vascular endothelial growth factor, and reduced airway collagen deposition and inhibited goblet cell hyperplasia in OVA‐induced asthma in mice. Mechanistically, integrin 3 contributes to the protective effect of MFG‐E8 in inhibiting airway inflammation and remodeling in OVA‐driven features of allergic asthma. Overall, MFG‐E8, as a candidate molecule to evaluate airway inflammation and remodeling, could be a potential target for the management and prevention of asthma exacerbations, suggesting that MFG‐E8/integrin β3 signaling may serve as a promising therapeutic agent for childhood asthma.
Percutaneous closure of residual shunting in a patient with a fenestrated atrial septal defect occluder

Rationale: Fenestrated atrial septal defect (ASD) occlusion has been performed in patients complicated with severe pulmonary hypertension (PH). Nevertheless, the persistent interatrial residual shunting in the fenestration might increase the risk of paradoxical embolism. Percutaneous closure of fenestrated ASD occluder (ASO) has not yet been reported. Patient concerns: A 26-year-old patient with a 25-mm ASD and severe PH underwent ASD closure using a Memory ASO with a waist of 32 and 6-mm custom-made fenestration. Echocardiography revealed the fenestration remained 6 mm and the pulmonary artery pressure decreased to the normal range at the 6-month follow-up. Diagnoses: Persistent interatrial residual shunting in ASO. Interventions: Percutaneous closure of residual interatrial shunting was performed using a waist of 8-mm ASO under guidance of TEE. Outcomes: The fenestration was successfully closed. Neither thromboembolism nor infection events were noted during the 12-month follow-up after the procedure. Lessons: This case illustrates that percutaneous closure of the residual shunting in fenestrated ASO was feasible and safe for short- and long-term.
Spore wall ultrastructure and development in a basal euphyllophyte: Psilophyton dawsonii from the Lower Devonian of Quebec (Canada).

PREMISE OF THE STUDY Euphyllophytes, a clade including living ferns, horsetails, and seed plants, have a rich fossil record going back to the Early Devonian. The euphyllophyte spore wall has a complex structure, the evolutionary origins of which are incompletely understood. Psilophyton is the best-characterized basal euphyllophyte genus; thus, data on this genus can inform current hypotheses on spore wall structure and development, which propose a bilayered spore wall organization of combined spore and sporangial origin for the ancestral euphyllophyte. METHODS We employed cellulose acetate peel sectioning of permineralized Lower Devonian (Emsian) Psilophyton dawsonii sporangia, combined with electron microscopy, to document spore wall structure and development. KEY RESULTS The Psilophyton dawsonii spore wall is bilayered. The inner spore wall is homogeneous, probably of lamellar construction. The outer spore wall, loosely attached to the inner wall, covers distal and equatorial spore areas, and has a foveolate base layer upon which stacks of sporopollenin lumps accrete centrifugally, forming the scaffolding for the final apiculate ornamentation. CONCLUSIONS This is the most complete account on spore wall structure, allowing developmental interpretations, in a basal euphyllophyte. The bipartite organization of the Psilophyton dawsonii spore wall reflects development as a result of two processes: an inner layer laid down by the spore cell and an outer layer of tapetal origin. Providing direct evidence on the spore wall of a basal euphyllophyte, these data confirm previous hypotheses and mark an empirically supported starting point for discussions of the evolution of spore wall development in euphyllophytes.
Thylakoid membrane lipid sulfoquinovosyl-diacylglycerol (SQDG) is required for full functioning of photosystem II in Thermosynechococcus elongatus

Sulfoquinovosyl-diacylglycerol (SQDG) is one of the four lipids present in the thylakoid membranes. Depletion of SQDG causes different degrees of effects on photosynthetic growth and activities in different organisms. Four SQDG molecules bind to each monomer of photosystem II (PSII), but their role in PSII function has not been characterized in detail, and no PSII structure without SQDG has been reported. We analyzed the activities of PSII from an SQDG-deficient mutant of the cyanobacterium Thermosynechococcus elongatus by various spectroscopic methods, which showed that depletion of SQDG partially impaired the PSII activity by impairing secondary quinone (QB) exchange at the acceptor site. We further solved the crystal structure of the PSII dimer from the SQDG deletion mutant at 2.1 Å resolution and found that all of the four SQDG-binding sites were occupied by other lipids, most likely PG molecules. Replacement of SQDG at a site near the head of QB provides a possible explanation for the QB impairment. The replacement of two SQDGs located at the monomer–monomer interface by other lipids decreased the stability of the PSII dimer, resulting in an increase in the amount of PSII monomer in the mutant. The present results thus suggest that although SQDG binding in all of the PSII-binding sites is necessary to fully maintain the activity and stability of PSII, replacement of SQDG by other lipids can partially compensate for their functions.
Bloodstream infections and trends of antimicrobial sensitivity patterns at Port Blair

PURPOSE: Bloodstream infection can range from inapparent bacteremia until fulminant septic shock with high mortality. Microorganisms present in circulating blood whether continuously, intermittently, or transiently are a threat to every organ in the body. Culture of blood is a vital tool to diagnose such infections. Drug susceptibility patterns help in rationalizing therapy. OBJECTIVE: The objective of this study was to perform bacteriological analysis and assess drug sensitivity patterns of isolates from blood stream infections. DESIGN: Retrospective observational study was conducted from May 2015 to February 2017 at a tertiary care hospital, Port Blair, India. Blood samples were collected with aseptic guidelines and cultured for 7 days. Growths were identified using standard biochemical tests and subjected to sensitivity testing according to Modified Kirby–Bauer's disk diffusion method. Data for the source of blood collection and duration of incubation were noted and compared. RESULTS: A total of 270 (14.24%) pathogens were isolated from 1895 bacteremia suspect patient blood specimens. Contamination was observed at a rate of 1.63%. Gram-positive cocci (60.37%) were predominant organisms recovered followed by Gram-negative Bacilli (36.29%) and Yeasts (3.33%). Staphylococcus aureus, CoNS, and Acinetobacter spp. were the primary pathogens isolated. Aminoglycosides, carbapenems, and glycopeptides were the most effective drugs for treating bacteremia. CONCLUSIONS: Successful treatment of sepsis depends on early diagnosis and proper antimicrobial therapy. Local knowledge of bacteriological profile and antimicrobial sensitivity patterns helps rationalize empiric treatment strategies.
Assessment of the Cerebral Hemodynamic Benefits of Carotid Artery Stenting for Patients with Preoperative Hemodynamic Impairment Using Cerebral Single Photon Emission Computed Tomography (SPECT) and Carbon Dioxide Inhalation

Background The aim of this study was to evaluate the effects of carotid artery angioplasty and carotid artery stenting (CAS) on cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) in patients with preoperative cerebrovascular hemodynamic impairment. Material/Methods Seventeen patients with unilateral severe internal carotid artery (ICA) stenosis and ipsilateral CVR impairment underwent CAS. CBF and CVR were measured by single photon emission computed tomography (SPECT) with inhalation of carbon dioxide (CO2) one week before and three months after CAS. Sixty-eight ROIs in the middle cerebral artery (MCA) territory were analyzed in 17 patients. Results Before CAS, CVR was impaired in all ROIs. CBF was impaired in 16 ROIs (23.5%). The percentage of ROIs with impaired CBF was significantly increased in patients with ≥90% carotid artery stenosis (p=0.047) without collateral flow through the circle of Willis (p=0.005). CAS significantly increased CVR in ROIs with a normal preoperative CBF and impaired CVR, indicating mild hemodynamic impairment (0.9±6.7% vs. 4.9±8.6%) (p=0.014). CAS significantly increased CBF in ROIs with preoperative impaired CBF and impaired CVR, indicating severe hemodynamic impairment (79.1±7.5% vs. 86.7±10.0%) (p<0.001). Following CAS, ROIs with normal CBF and impaired CVR had a significantly increased percentage of improved CVR (p=0.047); ROIs with impaired CBF and impaired CVR had a significantly increased percentage of improved CBF (p=0.027). Conclusions The severity of preoperative hemodynamic impairment, which is related to the degree of carotid artery stenosis and cerebral collateral flow, may influence hemodynamic benefits by CAS.