Miracle-dz/UniFAR-FTUs huggingface dataset:
The Capabilities and Characteristics of Helical Tomotherapy and Co-Planar Dual Arcs Volumetric-Modulated arc Therapy Associated with Hippocampal Sparing During Prophylactic Cranial Irradiation

Objective: To investigate the features of helical tomotherapy and co-planar dual Arcs volumetric-modulated arc therapy during prophylactic cranial irradiation associated with bilateral hippocampal tissue sparing. Materials and methods: Helical tomotherapy and co-planar dual arcs volumetric-modulated arc therapy treatment plans were generated with a dose of 30 Gy/10 fractions in 16 patients treated with prophylactic cranial irradiation. The dose to the bilateral hippocampal tissues, organs at risk, and planning target volume were determined when the average dose of bilateral hippocampal tissues was reduced by approximately 4 Gy as an observation point. Changes in dosimetry when sparing the bilateral hippocampal tissues were determined for both modalities. Results: When bilateral hippocampal tissues were restricted to 8 Gy, D40%mean-bilateral hippocampal tissues = 7.64 ± 0.41 Gy in helical tomotherapy, while D40%mean-bilateral hippocampal tissues = 10.96 ± 0.38 Gy in co-planar dual arcs volumetric-modulated arc therapy volumetric-modulated arc therapy. Helical tomotherapy was associated with significantly lower doses to organs at risk, including Dmean-bilateral hippocampal tissues (P = .03), D98%-bilateral hippocampal tissues (P = .01), D2%-bilateral hippocampal tissues (P = .01), Dmean-inner ear (P = .02), Dmean-parotid glands (P = .02), Dmax-lens (P = .02), and Dmax-brainstem (P = .02), but not Dmax-optic nerves (P = .87). Helical tomotherapy provided better target coverage, with lower average D2%-PTV (P = .02), higher average D98%-PTV (P = .02), and better conformal index (0.87 vs 0.84, P = .02) and homogeneity index (0.15 vs 0.21, P = .05). With smaller bilateral hippocampal tissues doses, the planning target volume dose changed across 3 dosimetry regions for both modalities; the plateau region (>20.0 Gy for helical tomotherapy versus >16.0 Gy for co-planar dual arcs volumetric-modulated arc therapy), gradient region (20.0-12.0 Gy vs 16.0-11.0 Gy), and falling region (<12.0 Gy vs <11.0 Gy). The average delivery duration of helical tomotherapy was almost 7.7 times longer than that of co-planar dual arcs volumetric-modulated arc therapy. Conclusions: Helical tomotherapy was better at sparing the bilateral hippocampal tissues and organs at risk and had better target coverage but a significantly longer treatment duration than co-planar dual arcs volumetric-modulated arc therapy. Further dose decreases in the bilateral hippocampal tissues would yield worse target dose coverage.
Plasma KRAS mutations predict the early recurrence after surgical resection of pancreatic cancer

ABSTRACT Background The technique to analyze circulating tumor DNA (ctDNA) in body fluid (so-called “liquid biopsy”) is recently developed. Aims Our aim was to assess the utility of liquid biopsy for predicting progression of pancreatic ductal adenocarcinoma (PDAC) after surgical resection or chemotherapy. Methods A total of 72 patients with PDAC were retrospectively enrolled for this study, 33 treated surgically and 39 given chemotherapy, either FOLFIRINOX (oxaliplatin/irinotecan/fluorouracil/leucovorin) or gemcitabine plus nab-paclitaxel. Prior to treatment, patients were screened for the presence of KRAS mutations (G12D and G12V) in plasma using droplet digital polymerase chain reaction, and outcomes were compared. Results KRAS mutations were identified in plasma samples of 12 patients (36%) underwent surgical resection. Patients with plasma KRAS mutations had significantly shorter disease-free survival (DFS) and overall survival (p < .01 and p = .01, respectively). Of 10 clinical variables analyzed, plasma KRAS mutation was the factor predictive of DFS in multivariate analysis (RR = 3.58, 95% CI: 1.36–9.60; p = .01). Although 12 patients (31%) given chemotherapy tested positive for plasma KRAS mutations, there was no demonstrable relation between plasma KRAS mutations and progression-free survival (PFS) or overall survival (OS) (p = .35 and p = .68, respectively). Conclusions In patients with PDAC, detection of KRAS mutations in plasma proved independently predictive of early recurrence after surgical resection but did not correlate with PFS following chemotherapy.
Rank and Match Outcomes of In-person and Virtual Anesthesiology Residency Interviews.

Background For the 2019-2020 interview season, the anesthesia residency program at Augusta University offered candidates a choice between in-person (IP) and video conference (VC) interviews to accommodate a greater number of qualified candidates. Methods The same applicant selection criteria were used for both interview types. However, we modified the informal interactions with residents, campus tours, and interview formats for VC interviews. We sought to compare the 2 methods by analyzing the respective costs, benefits, and match results. Results Of 159 candidates interviewed, we ranked 127 and matched with 12. The IP (n = 135) and VC (n = 24) groups were similar in gender distribution but not by the type of medical school, with more international medical graduates interviewing by VC than IP. There was no statistically significant difference between the 2 interview types for being ranked (81% of IP, 71% of VC) or matched (6% of IP, 17% of VC). US Medical Licensing Examination Step 1 and Step 2 scores and type of medical school did not affect the likelihood of being ranked or matched. Program costs per candidate were higher for the IP group ($431 for IP, $294 for VC). Conclusion Our single-center study indicates that the interview type did not affect the likelihood of a candidate being ranked by or matched to our program. Further, VC interviews were more cost-effective and time-effective than IP interviews. Our findings suggest that VC interviews are a viable alternative and should be an option for residency interviews.
Extended phenotyping does not preclude the occurrence of delayed haemolytic transfusion reactions in sickle cell disease

Delayed haemolytic transfusion reaction (DHTR) is a potentially life‐threatening complication of red blood cell (RBC) transfusions in sickle cell disease (SCD) and is classically induced by reactivation of previously formed antibodies. Improved antigenic matching has reduced alloimmunization and may reduce DHTR risk. We conducted a retrospective cohort study to investigate the incidence rate of DHTR in SCD patients receiving extended matched units (ABO/RhDCcEe/K/Fya/Jkb/S). Occasional transfusion episodes (OTE) between 2011 and 2020 were reviewed for occurrence of DHTR symptoms using four screening criteria: decreased Hb, increased lactate dehydrogenase (LDH), pain, and dark urine. We included 205 patients who received a cumulative number of 580 transfusion episodes of 1866 RBC units. During follow‐up, 10 DHTR events were observed. The incidence rate of DHTR was 13·8/1000 OTEs [95% confidence interval (CI): 7·37–22·2], with a cumulative incidence of 15·2% (95% CI: 8·4–24·0%) after 25 patients having received RBC units. One DHTR event was fatal (10%). Symptoms were misdiagnosed in four DHTR events (40%) as other acute SCD complications. Despite a lower incidence rate compared to most other studies, the incidence rate of DHTR in SCD remains high, in spite of extended matching of donor RBCs. Increased awareness of DHTR is of utmost importance to facilitate early diagnosis and, consequently, improve outcome.
Structure-based charge calculations for predicting isoelectric point, viscosity, clearance, and profiling antibody therapeutics

ABSTRACT The effect of hydrophobicity on antibody aggregation is well understood, and it has been shown that charge calculations can be useful for high-concentration viscosity and pharmacokinetic (PK) clearance predictions. In this work, structure-based charge descriptors are evaluated for their predictive performance on recently published antibody pI, viscosity, and clearance data. From this, we devised four rules for therapeutic antibody profiling which address developability issues arising from hydrophobicity and charged-based solution behavior, PK, and the ability to enrich for those that are approved by the U.S. Food and Drug Administration. Differences in strategy for optimizing the solution behavior of human IgG1 antibodies versus the IgG2 and IgG4 isotypes and the impact of pH alterations in formulation are discussed.
Conference on Nutrition, health and ageing – translating science into practice Symposium two: Anthropometric, lifestyle and dietary concerns in ageing – diagnostic and interventional considerations Fish, n -3 fatty acids, cognition and dementia risk: not just a ﬁ shy tale

With growing and ageing populations, the incidence of dementia is expected to triple globally by 2050. In the absence of effective drugs to treat or reverse the syndrome, dietary approaches which prevent or delay disease onset have considerable population health potential. Prospective epidemiological studies and mechanistic insight from experimental models strongly support a positive effect of a high ﬁ sh and long chain n -3 fatty acid (EPA and DHA) intake on a range of cognitive outcomes and dementia risk, with effect sizes equivalent to several years of ageing between the highest and lowest consumers. As reviewed here, an effect of EPA and DHA on neuroin ﬂ ammation and oxylipin production is likely to in part mediate the neurophysiological bene ﬁ ts. However, randomised controlled trials (RCTs) with EPA and DHA supplementation have produced mixed ﬁ ndings. Insight into the likely modulators of response to intervention and factors which should be considered for future RCTs are given. Furthermore, the impact of APOE genotype on disease risk and response to EPA and DHA supplementation is summarised. The prevalence of dementia is several-fold higher in APOE4 females (about 13 % Caucasian populations) relative to the general population, who are emerging as a subgroup who may particularly bene ﬁ t from DHA intervention, prior to the development of signi ﬁ cant pathology. DHA:
ANALYTICAL METHOD DEVELOPMENT FOR SIMULTANEOUS DETERMINATION OF UBIDECARENONE AND VITAMIN E ACETATE IN CAPSULE DOSAGE FORM BY HPLC

Objective: To develop and validate a new simple, accurate, precise and sensitive high performance liquid chromatographic method (HPLC) method for simultaneous estimation of ubidecarenone and vitamin E acetate in capsule dosage form as per international conference on harmonization (ICH) guidelines. Methods: The chromatographic separation of drugs were achieved using hypersil C8 column (250 mm x 4.6 mm, 5µ) in isocratic elution mode with a mobile phase of methanol: ethanol: n-hexane (80:10:10 v/v/v) at a flow rate of 1 ml/min with ultra-violet (UV) detection at 210 nm. Results: The optimized method produced sharp peaks with good resolution, minimum tailing factor and satisfactory retention time were found to be 5.745 min and 12.565 min for vitamin E acetate and ubidecarenone respectively. The method was linear in the range of 60-180 µg/ml for ubidecarenone and 20-60 µg/ml for vitamin E acetate with a correlation coefficient of 0.999 and 0.9993 respectively. Mean recoveries observed for ubidecarenone and vitamin E acetate were 99.85% and 99.73% respectively. The percentage relative standard deviation (% RSD) of peak area for system precision, method precision, and intermediate precision were found to be less than 0.37%. The lower degree of % RSD obtained has proved that the method was precise and robust. Conclusion: A new simple HPLC method was developed and validated as per ICH guidelines for the simultaneous estimation of ubidecarenone and vitamin E acetate and the method can be effectively applied for the routine analysis of active pharmaceutical ingredient (API) and formulations.
Pathological gallbladder wall thickening is associated with advanced chronic liver disease and independent of serum albumin

Increased gallbladder wall thickness (GBWT) is a common finding. Reported causes include advanced chronic liver disease (ACLD), ascites and hypalbuminemia. GBWT is a marker for the prediction of esophageal varices. It remains unclear which of these factors is the decisive driver of GBWT. We aim to investigate whether there is a predominant factor associated with the GBWT.
Is non-contrast-enhanced magnetic resonance imaging cost-effective for screening of hepatocellular carcinoma?

Introduction: Ultrasonography (US) is the current standard of care for imaging surveillance in patients at risk of hepatocellular carcinoma (HCC). Magnetic resonance imaging (MRI) has been explored as an alternative, given the higher sensitivity of MRI, although this comes at a higher cost. We performed a cost-effective analysis comparing US and dual-sequence non-contrast-enhanced MRI (NCEMRI) for HCC surveillance in the local setting. Methods: Cost-effectiveness analysis of no surveillance, US surveillance and NCEMRI surveillance was performed using Markov modelling and microsimulation. At-risk patient cohort was simulated and followed up for 40 years to estimate the patients’ disease status, direct medical costs and effectiveness. Quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio were calculated. Results: Exactly 482,000 patients with an average age of 40 years were simulated and followed up for 40 years. The average total costs and QALYs for the three scenarios — no surveillance, US surveillance and NCEMRI surveillance — were SGD 1,193/7.460 QALYs, SGD 8,099/11.195 QALYs and SGD 9,720/11.366 QALYs, respectively. Conclusion: Despite NCEMRI having a superior diagnostic accuracy, it is a less cost-effective strategy than US for HCC surveillance in the general at-risk population. Future local cost-effectiveness analyses should include stratifying surveillance methods with a variety of imaging techniques (US, NCEMRI, contrast-enhanced MRI) based on patients’ risk profiles.
Insulin acts as an atypical KCNQ1/KCNE1‐current activator and reverses long QT in insulin‐resistant aged rats by accelerating the ventricular action potential repolarization through affecting the β3‐adrenergic receptor signaling pathway

Insufficient‐heart function is associated with myocardial insulin resistance in the elderly, particularly associated with long‐QT, in a dependency on dysfunctional KCNQ1/KCNE1‐channels. So, we aimed to examine the contribution of alterations in KCNQ1/KCNE1‐current (IKs) to the aging‐related remodeling of the heart as well as the role of insulin treatment on IKs in the aged rats. Prolonged late‐phase action potential (AP) repolarization of ventricular cardiomyocytes from insulin‐resistant 24‐month‐old rats was significantly reversed by in vitro treatment of insulin or PKG inhibitor (in vivo, as well) via recovery in depressed IKs. Although the protein level of either KCNQ1 or KCNE1 in cardiomyocytes was not affected with aging, PKG level was significantly increased in those cells. The inhibited IKs in β3‐ARs‐stimulated cells could be reversed with a PKG inhibitor, indicating the correlation between PKG‐activation and β3‐ARs activation. Furthermore, in vivo treatment of aged rats, characterized by β3‐ARs activation, with either insulin or a PKG inhibitor for 2 weeks provided significant recoveries in IKs, prolonged late phases of APs, prolonged QT‐intervals, and low heart rates without no effect on insulin resistance. In vivo insulin treatment provided also significant recovery in increased PKG and decreased PIP2 level, without the insulin effect on the KCNQ1 level in β3‐ARs overexpressed cells. The inhibition of IKs in aged‐rat cardiomyocytes seems to be associated with activated β3‐ARs dependent remodeling in the interaction between KCNQ1 and KCNE1. Significant recoveries in ventricular‐repolarization of insulin‐treated aged cardiomyocytes via recovery in IKs strongly emphasize two important issues: (1) IKs can be a novel target in aging‐associated remodeling in the heart and insulin may be a cardioprotective agent in the maintenance of normal heart function during the aging process. (2) This study is one of the first to demonstrate insulin's benefits on long‐QT in insulin‐resistant aged rats by accelerating the ventricular AP repolarization through reversing the depressed IKs via affecting the β3‐ARs signaling pathway and particularly affecting activated PKG.
ALK Fusion Protein Expression in Lung Adenocarcinoma and its Correlation with EGFR Protein Expression

Aim: To determine ALK fusion protein and EGFR protein expression by Immunohistochemistry in lung adenocarcinoma. Materials and Method: In this retrospective study, ALK and EGFR expression was evaluated by immunohistochemistry in 101 Formalin Fixed Paraffin Embedded (FFPE) tissues of lung adenocarcinoma. Results: In this study 11% patients showed ALK fusion protein expression. In relation to clinical parameters, a higher positive expression was observed in patients with age <59, in male gender and tobacco users. Further, with pathological parameters a higher expression of ALK was observed in advanced stage and positive lymph node status. EGFR expression was noted in 72% patients. In relation to clinical parameters, higher EGFR expression was seen in patients with age >59 years, in male gender with tobacco habit. Further, with pathological parameters, a trend of higher EGFR expression was observed in patients with positive lymph node status (p=0.06). In this study 8% of patients had ALK and EGFR dual expression, which is uncommon. Conclusion: Small group of NSCLC patients harbour ALK rearrangements which are candidate for targeted therapy (Crizotinib). Moreover, co-expression of ALK with EGFR defines a specific subgroup of patients that needs distinct therapeutic strategies.
Whole-genome sequence analysis of Shiga toxin-producing Escherichia coli O157 strains isolated from wild deer and boar in Japan

The prevalence of Shiga toxin-producing Escherichia coli O157 (STEC O157) strains in wild deer and boar in Japan was investigated. STEC O157 strains were isolated from 1.9% (9/474) of the wild deer and 0.7% (3/426) of the wild boar examined. Pulsed-field gel electrophoresis (PFGE) analysis classified the wild deer and boar strains into five and three PFGE patterns, respectively. The PFGE pattern of one wild boar strain was similar to that of a cattle strain that had been isolated from a farm in the same area the wild boar was caught, suggesting that a STEC O157 strain may have been transmitted between wild boar and cattle. Clade analysis indicated that, although most of the strains were classified in clade 12, two strains were classified in clade 7. Whole-genome sequence (WGS) analysis indicated that all the strains carried mdfA, a drug resistance gene for macrolide antibiotics, and also pathogenicity-related genes similar to those in the Sakai strain. In conclusion, our study emphasized the importance of food hygiene in processing meat from Japanese wild animals for human consumption.
Rate of Development of Venous Thromboembolism in Lateral Skull Base Surgery

Venous thromboembolism (VTE) is a major cause of morbidity and mortality for surgical patients. This article aims to determine factors that may have contributed to the development of VTE in patients undergoing lateral skull base surgery, to assess the validity of the Caprini Risk Assessment Model (RAM) score in this subset of patients, and to determine the efficacy of mechanical DVT prophylaxis alone in preventing VTE.
A retrospective study of the spectrum of fungal keratitis in southeastern China.

BACKGROUND This study investigated the epidemiological characteristics, predisposing factors, clinical features, microbiological findings, and treatment outcomes of patients with fungal keratitis in southeastern China. METHODS A retrospective review was carried out on 718 patients diagnosed with fungal keratitis at the the First Affiliated Hospital of Fujian Medical University between January 2004 and December 2017. The sociodemographic data, predisposing factors, clinical details, microbiological findings, and treatment strategies were analyzed. RESULTS Fungal keratitis was diagnosed in 718 patients (442 male and 276 female; mean age, 41.4±13.1 years). Most patients came from rural areas (79.7%) and farm work was the main occupational activity (51.7%). Cases were more common during the harvest season between October and December (41.6%). Corneal trauma (73.7%), particularly injury with vegetative matter (51.5%), was the predominant predisposing factor. Corneal scrapings obtained from 621 patients were diagnosed as positive on direct microscopy using a 10% potassium hydroxide (KOH) wet mount preparation. The positive culture rate of corneal scrapings was 89.6%. Fungal isolates were Fusarium species in 444 eyes and Aspergillus species in 98 eyes. Antifungal medications were used to treat 529 patients and 189 patients received surgery. CONCLUSIONS Fungal keratitis is a leading cause of infective corneal ulcers in southeastern China. Corneal trauma was the major predisposing factor and direct microscopic examination was a rapid and sensitive method for diagnosis. The species Fusarium was the most common fungal isolate. Antifungal medication was an effective method for treating early and mild cases.
Controls for Phylogeny and Robust Analysis in Pareto Task Inference

Abstract Understanding the tradeoffs faced by organisms is a major goal of evolutionary biology. One of the main approaches for identifying these tradeoffs is Pareto task inference (ParTI). Two recent papers claim that results obtained in ParTI studies are spurious due to phylogenetic dependence (Mikami T, Iwasaki W. 2021. The flipping t-ratio test: phylogenetically informed assessment of the Pareto theory for phenotypic evolution. Methods Ecol Evol. 12(4):696–706) or hypothetical p-hacking and population-structure concerns (Sun M, Zhang J. 2021. Rampant false detection of adaptive phenotypic optimization by ParTI-based Pareto front inference. Mol Biol Evol. 38(4):1653–1664). Here, we show that these claims are baseless. We present a new method to control for phylogenetic dependence, called SibSwap, and show that published ParTI inference is robust to phylogenetic dependence. We show how researchers avoided p-hacking by testing for the robustness of preprocessing choices. We also provide new methods to control for population structure and detail the experimental tests of ParTI in systems ranging from ammonites to cancer gene expression. The methods presented here may help to improve future ParTI studies.