Miracle-dz/UniFAR-FTUs huggingface dataset:
Retrospective analysis of hypofractionated stereotactic radiotherapy for tumors larger than 2 cm

ABSTRACT Stereotactic radiosurgery for large brain metastases (BM) not amenable to surgical resection is associated with limited local control and neurotoxicity, while hypofractionated stereotactic radiotherapy (HFSRT) has emerged as a promising option. We retrospectively evaluated 61 patients with BM larger than 2 cm in the maximum diameter, who were treated with HFSRT (mainly 35 Gy/5 fractions) in our center between 2006–2016, focusing on the effect of BM size on outcomes. Eligible patients were divided according to the maximum BM diameter (group A [23 patients]: ≥3 cm, group B [22 patients]: <3 cm) to assess the relationship between tumor size and prognosis or safety. The primary outcome was the local control rate (LCR), and secondary outcomes were the response rate (RR), brain progression-free survival (BPFS), median survival time (MST), and radionecrosis (RN). Univariate and multivariate analyses for LCR were conducted using Cox’s proportional hazards model. In the 45 eligible patients (58 lesions) enrolled in this study, the RR was 86.4% with an overall LCR of 64.7% at 12 months (67.1% for group A and 61.5% for group B [p = 0.45]). The median BPFS and MST were 11.6 and 14.2 months, respectively. Univariate analyses revealed that female patients and gynecological cancer patients had poorer LCR, but they were not significantly independent prognostic factors (p = 0.06, 0.09, respectively). Two patients (4.4%) experienced RN that was detected more than 4 years after HFSRT. We conclude that HFSRT is safe for large BM but further studies are needed to determine optimal doses and fractions.
Genome aging: somatic mutation in the brain links age-related decline with disease and nominates pathogenic mechanisms.

Aging is a mysterious process, not only controlled genetically but also subject to random damage that can accumulate over time. While DNA damage and subsequent mutation in somatic cells were first proposed as drivers of aging more than 60 years ago, whether and to what degree these processes shape the neuronal genome in the human brain could not be tested until recent technological breakthroughs related to single-cell whole-genome sequencing. Indeed, somatic single-nucleotide variants (SNVs) increase with age in the human brain, in a somewhat stochastic process that may nonetheless be controlled by underlying genetic programs. Evidence from the literature suggests that in addition to demonstrated increases in somatic SNVs during aging in normal brains, somatic mutation may also play a role in late-onset, sporadic neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. In this review, we will discuss somatic mutation in the human brain, mechanisms by which somatic mutations occur and can be controlled, and how this process can impact human health.
Protein tyrosine phosphatase non‐receptor type 22 (PTPN22) gene polymorphisms in liver transplant donors and impact on acute cellular liver transplant rejection

The PTPN22 gene encodes the lymphoid protein tyrosine phosphatase involved in regulation the immune response. The single nucleotide polymorphisms (SNPs) rs1217388, rs1310182, rs2476601, and rs2488457 are located within the PTPN22 gene. We investigated whether these SNPs in liver transplant donors are associated with acute cellular rejection in the recipients. The SNPs were analyzed in donors (n = 104) of recipients who did not develop an acute cellular rejection and in donors (n = 53) of corresponding recipients developing an acute cellular rejection. No significant differences in genotype and allele frequencies of these SNPs were detected in either of the group. Our data suggest that these SNPs in liver transplant donors have no impact on the susceptibility of acute cellular liver transplant rejection.
Polymicrobial bacteremia after treatment of transcatheter arterial chemoembolization

Abstract Rationale: Bacteremia caused by polymicrobial infections are rare but dangerous. We report a case of hepatic abscess combined with polymicrobial bacteremia in a 49-year-old male patient after surgery and transcatheter arterial chemoembolization (TACE). Patient concerns: The patient was admitted to hospital with metastatic liver cancer for periodic chemotherapy and developed a high fever and tenderness to the liver following surgery and TACE. Diagnosis: Hepatic abscess combined with polymicrobial bacteremia. Interventions: The clinician formulated a therapy in accordance with the drug susceptibility test and the empirical drug use for anaerobic bacteria. A comprehensive treatment plan was adopted, on the basis of the combination of nitrazole and imipenem as anti-infection drugs as well as continuous abscess drainage. Outcomes: After comprehensive therapy, the patient was ultimately discharged without any residual symptoms. Lessons: Bloodstream infection caused by multiple bacteria increases the difficulty of anti-infection treatments, leading to poor treatment outcome and high mortality. Therefore, a fast and accurate diagnosis of polymicrobial bacteremia is key for initiation of an effective antimicrobial treatment. Additionally, pre-operative prophylactic antibiotics are advisable when patients have a history of abdominal surgery and are immune-compromised.
Epidemiological evidence that common HPV types may be common because of their ability to evade immune surveillance: Results from the Women's Interagency HIV study

Infection by human papillomavirus (HPV) type 16, the most oncogenic HPV type, was found to be the least affected by HIV‐status and CD4 count of any of the approximately 13 oncogenic HPV types. This relative independence from host immune status has been interpreted as evidence that HPV16 may have an innate ability to avoid the effects of immunosurveillance. However, the impact of immune status on other individual HPV types has not been carefully assessed. We studied type‐specific HPV infection in a cohort of 2,470 HIV‐positive (HIV[+]) and 895 HIV‐negative (HIV[−]) women. Semi‐annually collected cervicovaginal lavages were tested for >40 HPV types. HPV type‐specific prevalence ratios (PRs), incidence and clearance hazard ratios (HRs), were calculated by contrasting HPV types detected in HIV[+] women with CD4 < 200 to HIV[−] women. HPV71 and HPV16 prevalence had the weakest associations with HIV‐status/CD4 count of any HPV, according to PRs. No correlations between PRs and HPV phylogeny or oncogenicity were observed. Instead, higher HPV type‐specific prevalence in HIV[−] women correlated with lower PRs (ρ = −0.59; p = 0.0001). An alternative (quadratic model) statistical approach (PHIV+ = a*PHIV− + b*PHIV−2; R2 = 0.894) found similar associations (p = 0.0005). In summary, the most prevalent HPV types in HIV[−] women were the types most independent from host immune status. These results suggest that common HPV types in HIV[−] women may have a greater ability to avoid immune surveillance than other types, which may help explain why they are common.
Dosimetric quality and delivery efficiency of robotic radiosurgery for brain metastases: Comparison with C‐arm linear accelerator based plans

Abstract The incidence of brain metastases is increasing and various treatment modalities exist for brain metastases. The aim of this study was to investigate the dosimetric quality and delivery efficiency of robotic radiosurgery (CyberKnife) for multiple brain metastases compared with C‐arm linear accelerator (linac) based plans. C‐arm linac based plans included intensity‐modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT) and non‐coplanar VMAT with 1, 3 and 5 non‐coplanar arcs, respectively (NC1, NC3 and NC5). For 20 patients, six plans with a prescription dose of 30 Gy in three fractions were generated. The gradient index (GI), conformity index (CI), maximum dose (Dmax) of organs at risk (OARs), normal brain tissue volume (V3 Gy–V24 Gy), monitor units (MUs) and beam on time (BT) were evaluated. The GI of CyberKnife plans (3.60 ± 0.70) was lower than IMRT (6.21 ± 2.26, P < 0.05), VMAT (6.04 ± 1.93, P < 0.05), NC1 (5.16 ± 1.71, P < 0.05), NC3 (5.02 ± 1.59, P < 0.05) and NC5 (5.03 ± 1.72, P < 0.05). The CI of the VMAT plans (both coplanar and non‐coplanar) was larger than IMRT and CK plans. The Dmax for most OARs of the CyberKnife plan was lower than the C‐arm linac based plans, although some differences were not statistically significant. The normal brain tissue volume of CyberKnife plan was lower than the C‐arm linac based plans, and the normal brain tissue volume of non‐coplanar VMAT plans was lower than IMRT and VMAT plans at high‐moderate dose level. However, the MUs and BT of CyberKnife plans was more than C‐arm linac based plans. CyberKnife plan was better than C‐arm linac based plans in protecting normal brain tissue and OARs for patients with multiple brain metastases. C‐arm linac based plan with non‐coplanar arc provided better protection of normal brain tissue than coplanar plan. However, the BT of CyberKnife plan was longer than C‐arm linac based plans.
Practical Nutrition Knowledge Mediates the Relationship Between Sociodemographic Characteristics and Diet Quality in Adults: A Cross-Sectional Analysis

Purpose: To investigate the direct and indirect effects of sociodemographic/health factors on diet quality through practical nutrition knowledge (PNK) about how to compose a balanced meal. Design: A cross-sectional study using data from an online survey of the 10 000 Steps cohort (data collected November-December 2016). Setting: Australia. Participants: Adults (n = 8161). Response rate was 16.7%. Measures: Self-reported lifestyle, health, and sociodemographic characteristics, including diet quality and PNK. Analysis: The PROCESS macro for SPSS was used to conduct the mediation analyses. Results: Better diet quality was associated with being female, older, more highly educated, and having a lower body mass index. Mediation analysis showed that PNK significantly mediated the associations between sex (a*b = 0.54, 95% confidence interval [CI] = 0.39-0.70) and education (vocational education: a*b = 0.22, 95% CI = 0.12-0.35, university: a*b = 0.48, 95% CI = 0.35-0.64), and diet quality. Practical nutrition knowledge suppressed the association between age and diet quality (a*b = −0.03, 95% CI = −0.04 to −0.03). Conclusion: Variations in diet quality between sociodemographic groups were partially explained by differences in PNK, suggesting that focusing public health efforts on increasing this specific knowledge type might be promising.
Laparoscopic treatment of median arcuate ligament syndrome: a systematic review.

INTRODUCTION Median arcuate ligament syndrome (MALS), is an uncommon condition caused by the extrinsic compression of the celiac trunk (CT) and celiac ganglion, secondary to an anatomical abnormality of the median arcuate ligament fibres. It is characterized by postprandial epigastric pain, chronic abdominal pain, weight loss, nausea and vomiting. MALS is typically diagnosed after the exclusion of other, more common conditions; however, a variety of imaging and diagnostic modalities, including duplex ultrasonography, computed tomography angiography, magnetic resonance angiography, gastric tonometry and angiography can suggest findings consistent with MALS. EVIDENCE ACQUISITION Laparoscopic approach has been proposed as the option of choice for the treatment of these patients. A systematic review of the international literature regarding this modality of treatment is presented here. EVIDENCE SYNTHESIS 504 cases have been included, and several principles are suggested to improve the management. The advantages of this minimally invasive technique include short operative time (136.0 minutes, range 70-242), shorter hospital stay (3.8 days, range 0.5-7) and low rate of conversion to open surgery (4.2%). CONCLUSIONS Various treatment modalities are available to decompress the celiac trunk. Although open surgery has been traditionally accepted as the gold standard, laparoscopic division of the MALS has proven equal results. Others have described different treatment modalities, including bypass surgery and endovascular procedures (angioplasty or stent placement). Laparoscopic approaches to correct MALS are feasible and safe. It may be the preferred modality of treatment in view of its lack of morbidity, shorter hospital stay and good results.
Does anogenital distance change with age?

It was known that in animals, anogenital distance (AGD), an indicator of prenatal androgen environment, was a stabile phenotype that persists throughout life. However, it is not known whether this applies to humans. In this study, we aimed to investigate whether anogenital distance is stable or not in males. We evaluated a total of 130 men targeted for group 1 (fathers) and group 2 (sons) in each 65 participants. AGD, the distance from anus to the posterior base of the scrotum, was measured with digital calipers. Anthropometric characteristics and testosterone levels of groups were recorded. We studied anogenital index (AGI), by dividing AGD by BMI to control bias of the weight and height, which could influence the measurement of AGD. The mean age of fathers was 61.5 ± 10.2 and that of children was 32.1 ± 5.48 (p = .00). The mean AGD scores were 55.46 ± 10.36 vs. 60.21 ± 10.04 (p = .09) and the mean total testosterone levels were 3.6 ± 1.47 vs. 5.45 ± 2.3 (p = .00) in group 1 and 2 respectively. There was no significant difference in height and weight between the two groups. AGD decreases with age, but further longitudinal studies are needed.
Self-Compassion in PLWH: Less Internalized Shame and Negative Psychosocial Outcomes

Abstract People living with HIV (PLWH) may experience internalized shame, which has been associated with negative psychosocial outcomes. Some of these psychosocial outcomes also are linked with worsening disease. Self-compassion, however, is the antithesis of internalizing shame, with elements of self-compassion (self-kindness, mindfulness, common humanity) at odds with indicators of internalized shame (negative beliefs about the self, desire to withdraw or avoid emotion, feelings of isolation). Therefore, we examined whether self-compassion among PLWH was associated with lower levels of internalized shame and, in turn, better psychosocial outcomes. We examined these relations using cross-sectional data collected from 181 PLWH living in the US via their participation in an online survey. Results revealed initial support for lower levels of internalized shame as potential mechanism that may explain how self-compassion comes to be associated with better outcomes among PLWH. Given self-compassion can be induced through intervention, we discuss how future research and clinical work with PLWH might address shame and improve outcomes.
Community-wide Screening for Tuberculosis in a High-Prevalence Setting.

BACKGROUND The World Health Organization has set ambitious targets for the global elimination of tuberculosis. However, these targets will not be achieved at the current rate of progress. METHODS We performed a cluster-randomized, controlled trial in Ca Mau Province, Vietnam, to evaluate the effectiveness of active community-wide screening, as compared with standard passive case detection alone, for reducing the prevalence of tuberculosis. Persons 15 years of age or older who resided in 60 intervention clusters (subcommunes) were screened for pulmonary tuberculosis, regardless of symptoms, annually for 3 years, beginning in 2014, by means of rapid nucleic acid amplification testing of spontaneously expectorated sputum samples. Active screening was not performed in the 60 control clusters in the first 3 years. The primary outcome, measured in the fourth year, was the prevalence of microbiologically confirmed pulmonary tuberculosis among persons 15 years of age or older. The secondary outcome was the prevalence of tuberculosis infection, as assessed by an interferon gamma release assay in the fourth year, among children born in 2012. RESULTS In the fourth-year prevalence survey, we tested 42,150 participants in the intervention group and 41,680 participants in the control group. A total of 53 participants in the intervention group (126 per 100,000 population) and 94 participants in the control group (226 per 100,000) had pulmonary tuberculosis, as confirmed by a positive nucleic acid amplification test for Mycobacterium tuberculosis (prevalence ratio, 0.56; 95% confidence interval [CI], 0.40 to 0.78; P<0.001). The prevalence of tuberculosis infection in children born in 2012 was 3.3% in the intervention group and 2.6% in the control group (prevalence ratio, 1.29; 95% CI, 0.70 to 2.36; P = 0.42). CONCLUSIONS Three years of community-wide screening in persons 15 years of age or older who resided in Ca Mau Province, Vietnam, resulted in a lower prevalence of pulmonary tuberculosis in the fourth year than standard passive case detection alone. (Funded by the Australian National Health and Medical Research Council; ACT3 Australian New Zealand Clinical Trials Registry number, ACTRN12614000372684.).
Comorbidities of HIV infection: role of Nef-induced impairment of cholesterol metabolism and lipid raft functionality

Combination antiretroviral therapy has dramatically changed the outcome of HIV infection, turning it from a death sentence to a manageable chronic disease. However, comorbidities accompanying HIV infection, such as metabolic and cardio-vascular diseases, as well as cognitive impairment, persist despite successful virus control by combination antiretroviral therapy and pose considerable challenges to clinical management of people living with HIV. These comorbidities involve a number of pathological processes affecting a variety of different tissues and cells, making it challenging to identify a common cause(s) that would link these different diseases to HIV infection. In this article, we will present evidence that impairment of cellular cholesterol metabolism may be a common factor driving pathogenesis of HIV-associated comorbidities. Potential implications for therapeutic approaches are discussed.
Expression of connective tissue growth factor as a prognostic indicator and its possible involvement in the aggressive properties of epithelial ovarian carcinoma

Recently, connective tissue growth factor (CTGF) was demonstrated to be associated with aggressive characteristics, including proliferation, invasion and metastasis, in a number of malignancies. Here, we investigated the expression and function of CTGF in epithelial ovarian carcinoma (EOC) to clarify its molecular mechanism and clinical significance. Paraffin sections from clinical samples of EOC (N=104) were immunostained with the CTGF antibody, and then the staining positivity was semiquantitatively examined. Moreover, we explored the role of CTGF expression in the migration-promoting effect on and chemoresistance of EOC cells. The results revealed that of the 104 EOC patients, the low and high CTGF staining expression rates were 65 (62.5%) and 39 (37.5%), respectively. Patients belonging to the higher-level CTGF group showed poorer progression-free (PFS) and overall survival (OS) rates than those in the lower-level group [PFS (log-rank: P=0.0076) and OS (log-rank: P=0.0078), respectively]. Multivariable analysis showed that CTGF expression was a significant predictor of poorer PFS and OS [PFS: HR (high vs. low): 1.837, 95% CI: 1.023–3.289 (P=0.0418); OS: HR: 2.141, 95% CI: 1.077–4.296 (P=0.0300)]. In in vitro studies, in acquired paclitaxel (PTX)-resistant EOC cells, the silencing of CTGF expression led to the restoration of PTX sensitivity. Furthermore, we confirmed that the TGF-β-dependent migration-promoting effect on these CTGF-depleted cells was completely inhibited. In conclusion, the results of the present study suggest the possible involvement of CTGF in the migration-promoting effect and chemoresistance of EOC, suggesting that it may be a target for overcoming the malignant properties of EOC.
Prospective natural history study of C9orf72 ALS clinical characteristics and biomarkers

Objective To define the natural history of the C9orf72 amyotrophic lateral sclerosis (C9ALS) patient population, develop disease biomarkers, and characterize patient pathologies. Methods We prospectively collected clinical and demographic data from 116 symptomatic C9ALS and 12 non–amyotrophic lateral sclerosis (ALS) full expansion carriers across 7 institutions in the United States and the Netherlands. In addition, we collected blood samples for DNA repeat size assessment, CSF samples for biomarker identification, and autopsy samples for dipeptide repeat protein (DPR) size determination. Finally, we collected retrospective clinical data via chart review from 208 individuals with C9ALS and 450 individuals with singleton ALS. Results The mean age at onset in the symptomatic prospective cohort was 57.9 ± 8.3 years, and median duration of survival after onset was 36.9 months. The monthly change was −1.8 ± 1.7 for ALS Functional Rating Scale–Revised and −1.4% ± 3.24% of predicted for slow vital capacity. In blood DNA, we found that G4C2 repeat size correlates positively with age. In CSF, we observed that concentrations of poly(GP) negatively correlate with DNA expansion size but do not correlate with measures of disease progression. Finally, we found that size of poly(GP) dipeptides in the brain can reach large sizes similar to that of their DNA repeat derivatives. Conclusions We present a thorough investigation of C9ALS natural history, providing the basis for C9ALS clinical trial design. We found that clinical features of this genetic subset are less variant than in singleton ALS. In addition, we identified important correlations of C9ALS patient pathologies with clinical and demographic data.
Does Listening to Music Regulate Negative Affect in a Stressful Situation? Examining the Effects of Self-Selected and Researcher-Selected Music Using Both Silent and Active Controls.

BACKGROUND Stress and anxiety are increasingly common among young people. The current research describes two studies comparing the effects of self-selected and researcher-selected music on induced negative affect (state anxiety and physiological arousal), and state mindfulness. METHOD In Study 1, 70 undergraduates were randomly assigned to one of three conditions: researcher-selected music, self-selected music, or a silent control condition. In Study 2, with 75 undergraduates, effects of music were compared to an active control (listening to a radio show). Negative affect was induced using a speech preparation and arithmetic task, followed by music listening or control. Self-reported anxiety and blood pressure were measured at baseline, post-induction, and post-intervention. Study 2 included state mindfulness as a dependent measure. RESULTS Study 1 indicated that participants who listened to music (self-selected and researcher-selected) reported significantly greater anxiety reduction than participants in the silent control condition. Music did not reduce anxiety compared to an active control in Study 2. However, music listening significantly increased levels of state mindfulness, which predicted lower anxiety after self-selected music listening. CONCLUSIONS Music may provide regulation in preparation for stressful events. Yet, the results of Study 2 indicate that other activities have similar benefits, and shows, for the first time, that music listening increases mindfulness following a stressor.