Miracle-dz/UniFAR-FTUs huggingface dataset:
Levels of Urinary Biomarkers of Oxidatively Generated Damage to DNA and RNA in Different Groups of Workers Compared to General Population

(1) Background: The products of guanine oxidation in DNA and RNA excreted in urine are 8-oxo-7,8-dihydroguanine (8-oxoGua), 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodGuo). Despite intra and inter-individual variability, it is possible to identify situations that significantly increase the levels of these compounds when comparing urinary concentrations of some workers to those of the general population. (2) Methods: urines from gasoline pump attendants (58 from Saudi Arabia and 102 from Italy), 24 workers of a fiberglass reinforced plastics plant, 17 painters and 6 divers were analyzed by HPLC/MS-MS. To test the individual variability, two subjects provided daily samples for one month, and 132 urine samples from the general population were analyzed. (3) Results: We summarized the results for each biomarker, and found the following were statistically higher than in the general population: 8-oxoGua in fiberglass and Italian gasoline workers; 8-oxodGuo in fiberglass and both Saudi Arabian and Italian gasoline workers; 8-oxoGuo in fiberglass workers, both Saudi Arabian and Italian gasoline workers, and painters after the working shift. (4) Conclusions: these results confirm that both 8-oxodGuo and 8-oxoGuo are valuable biomarkers for occupational exposures to dangerous chemicals and seem to suggest that 8-oxoGuo, related to RNA oxidation, is a suitable biomarker to evaluate short term, reversible effects of occupational exposures even within the health-based limit values.
The characteristics of captopril challenge test–positive patients using various criteria

Introduction: The captopril challenge test (CCT) is the major confirmatory test for primary aldosteronism (PA), and frequently carried out because of its convenience. However, it presents false-negative results with a certain probability, and as there are many criteria for CCT, it is not concluded yet which criteria to use. Materials and methods: A total of 71 PA patients were evaluated. We compared CCT-positive and CCT-negative patients in the following three criteria: plasma aldosterone/renin ratio (ARR) >200 after the CCT (criterion 1); plasma aldosterone concentration (PAC) >120 pg/ml after the CCT (criterion 2); and PAC suppression <30% of PAC before CCT (criterion 3). Results: The positive rate was 70.4%, 64.8% and 54.9% for criterion 1, criterion 2 and criterion 3, respectively. With criterion 1, the baseline plasma renin activity was lower, thus baseline ARR was higher in CCT-positive patients. With criterion 2, PAC was higher and estimated sodium intake and K were lower in CCT-positive patients. With criterion 3, K and PAC were lower in CCT-positive patients. Although it was not significant, in the patients with high sodium intake, the positive rate of criterion 1 was higher than that of the other criteria. Conclusions: ARR>200 is the valuable criterion for the diagnosis of PA.
Ocular biometry characteristics and corneal astigmatisms in cataract surgery candidates at a tertiary care center in North-East India

Purpose: The purpose of this study is to determine the ocular biometry characteristics and corneal astigmatisms using partial coherence laser interferometry in patients aged 40 years or above undergoing cataract surgery in a medical college in North-East India. Methods: In a hospital-based cross-sectional study, ocular biometry characteristics such as axial length (AL), anterior chamber depth (ACD), white-to-white (WTW) diameter, corneal power (K), and corneal astigmatisms (D) of consecutive eligible cataract patients in a medical college in North-East India between January 2015 and December 2017 were determined using the intraocular lens (IOL) master. Height and weight were also measured. Results: A cross-sectional study evaluated ocular biometry characteristics of 641 eyes in 641 eligible patients. The mean age was 64.04 ± 10.81 years. The mean AL, ACD, WTW, corneal power, IOL power, and body mass index (BMI) were 23.34 ± 1.12 mm, 3.12 ± 0.39 mm, 11.92 ± 0.54 mm, 44.41 ± 1.50 diopter (D), 20.53 ± 2.79 D, and 26.12 ± 4.32, respectively. Against-the-rule, with-the-rule, and oblique astigmatisms were 48.4%, 33.2%, and 18.4%, respectively. Corneal astigmatism of ≥1 D was found in 292 eyes (45.55%) and >1.5 D in 182 eyes (28.39%). AL had statistically significant correlation with ACD, WTW, K, IOL power, height and weight but not with age. By multivariate analysis, AL was found to be associated with ACD, WTW, K and IOL power (P ≤ 0.05). The mean AL was negatively correlated with the mean K (R-square 0.138). Conclusion: This study is likely to provide the initial normative data for ocular biometry values in Indian adults 40 years or above, because such data is lacking in Indians using the IOL master. This will also help ophthalmologists in planning and improving the quality of surgical outcomes in phacoemulsification and phacorefractive surgeries by choosing the appropriate IOL and incision location.
Evolution of renal function under direct‐acting antivirals treatment for chronic hepatitis C: A real‐world experience

Renal toxicity of direct‐acting antivirals (DAAs) in chronic hepatitis C (CHC) patients has not been well‐characterized. The aim of this study was to assess renal safety of DAAs in an Asian CHC patient cohort. Data from CHC patients (n = 1536) treated with DAAs were used in this retrospective study. Serial estimated glomerular filtration rate (eGFR) at pretreatment (1‐year prior to treatment), baseline, end of treatment (EOT), and 12 weeks after treatment (SVR12) was evaluated. While a significant decrease in eGFR from baseline to EOT (84.8 → 81.8 mL/min/1.73 m2, P < .001) was observed; subsequently, a slight rise at SVR12 (84.3 mL/min/1.73 m2) was also evident. Changes in eGFR after DAA treatment were similar to those seen in PrOD, DCV/ASV and GZP/EBV regimens, except in the SOF‐based regimen wherein eGFR remained unchanged from EOT to SVR12, especially in liver transplant recipients. Multivariate analysis revealed that age >65 years (OR = 1.862, P = .011), baseline eGFR ≥ 60 mL/min/1.73 m2 (OR = 2.684, P = .023), and liver transplant (OR = 3.894, P = .001) were independent risk factors for deteriorating renal function. In conclusion, DAA treatment led to a significant decline in eGFR at EOT but was followed by a slight rise at 12 weeks after treatment. A similar trend was observed with PrOD, DCV/ASV and GZP/EBV, but not in SOF‐based regimens. As age >65 years, baseline eGFR ≥ 60 mL/min/1.73 m2 and liver transplantation are significant risk factors for deterioration in renal function, we strongly advice close monitoring of renal function in these populations.
Peripheral T-Cell Lymphoma Arising in Patients With Chronic Lymphocytic Leukemia.

OBJECTIVES To describe three further cases of anaplastic large cell lymphoma (ALCL) occurring in patients with preexisting chronic lymphocytic leukemia (CLL). We also reviewed the literature of previously published cases. METHODS We discuss the clinical features, histopathology, and outcomes for three patients with ALCL and CLL from Perth, Australia. The cases were also included in a literature review of existing cases and comparisons were made with our cohort. RESULTS The three patients included two men (aged 77 and 74 years) and one woman (aged 66 years). All had a history of untreated CLL with diagnosis established 4 to 16 years before. They had lymphadenopathy and/or cutaneous/soft tissue lesions that proved to be ALCL, ALK+ (one case) or ALCL, ALK- (two cases). CONCLUSIONS Further research is required in this area to establish prognostic and management recommendations. Increasing numbers of cases are being described. Positron emission tomography with computed tomography was not useful in our cohort for diagnosing progression.
Targeting Autophagy in Cancer: Recent Advances and Future Directions.

Autophagy, a multistep lysosomal degradation pathway that supports nutrient recycling and metabolic adaptation, has been implicated as a process that regulates cancer. Although autophagy induction may limit the development of tumors, evidence in mouse models demonstrates that autophagy inhibition can limit the growth of established tumors and improve response to cancer therapeutics. Certain cancer genotypes may be especially prone to autophagy inhibition. Different strategies for autophagy modulation may be needed depending on the cancer context. Here, we review new advances in the molecular control of autophagy, the role of selective autophagy in cancer, and the role of autophagy within the tumor microenvironment and tumor immunity. We also highlight clinical efforts to repurpose lysosomal inhibitors, such as hydroxychloroquine, as anticancer agents that block autophagy, as well as the development of more potent and specific autophagy inhibitors for cancer treatment, and review future directions for autophagy research.Significance: Autophagy plays a complex role in cancer, but autophagy inhibition may be an effective therapeutic strategy in advanced cancer. A deeper understanding of autophagy within the tumor microenvironment has enabled the development of novel inhibitors and clinical trial strategies. Challenges and opportunities remain to identify patients most likely to benefit from this approach.
Motivational factors modulate left frontoparietal network during cognitive control in cocaine addiction

Cocaine addiction is characterized by alterations in motivational and cognitive processes involved in goal‐directed behavior. Recent studies have shown that addictive behaviors can be attributed to alterations in the activity of large functional networks. The aim of this study was to investigate how cocaine addiction affected the left frontoparietal network during goal‐directed behavior in a stop‐signal task (SST) with reward contingencies by correct task performance. Twenty‐eight healthy controls (HC) and 30 abstinent cocaine‐dependent patients (ACD) performed SST with monetary reward contingencies while undergoing a functional magnetic resonance imaging scan. The results showed that the left frontoparietal network (FPN) displayed an effect of cocaine addiction depending on reward contingencies rather than inhibition accuracy; and, second, we observed a negative correlation between dependence severity and the modulation of the left FPN network by the monetary reward in ACD. These findings highlight the role of the left FPN in the motivational effects of cocaine dependence.
Genetic Screening in a Large Chinese Cohort of Childhood Onset Hypoparathyroidism by Next‐Generation Sequencing Combined with TBX1‐MLPA

At least 15 candidate genes have been implicated in hypoparathyroidism (HP). However, comprehensive screening of causative genes for HP is lacking. Here, we investigated the genotype spectrum in a large group of Chinese patients with childhood onset HP. A total of 173 patients with childhood onset HP were analyzed using targeted next‐generation sequencing (NGS), including 15 candidate genes combined with multiplex ligation‐dependent probe amplification (MLPA) of the TBX1 gene. Twenty‐seven pathogenic or likely pathogenic mutations in five genes (TBX1, AIRE, GATA3, FAM111A, and CASR) including 13 novel variants in 23 patients, and 12 variants of uncertain clinical significance in five genes (GATA3, CASR, FAM111A, GCM2, and PTH) in 11 patients, were identified by NGS. Additionally, an entire gene deletion of TBX1 in 25 patients was found by TBX1‐MLPA. Combined with clinical data, 26 (15.0%) cases of DiGeorge syndrome (OMIM #188400), nine (5.2%) autoimmune polyglandular syndrome type 1 (OMIM #240300), eight (4.6%) autosomal dominant hypocalcemia type 1 (OMIM #601198), four (2.3%) hypoparathyroidism‐deafness‐renal dysplasia syndrome (OMIM #146255), and one (0.6%) Kenny‐Caffey syndrome type 2 (OMIM #127000) were verified. Among them, 16 of 26 (61.5%) DiGeorge syndrome cases were undiagnosed due to the lack of obvious clinical clues before genetic testing. The onset age of patients with mutations (median [interquartile range], 2.8 [0.1, 9.6] years) was significantly earlier than those without mutations (13.0 [8.8, 15.0] years) (p < 0.001). Family history, early onset age, especially prior to 5 years old, and extraparathyroid manifestations were clues for hereditary HP. The combined targeted NGS and TBX‐1 MLPA were conveniently and effectively used for comprehensive genetic screening in this large Chinese cohort of childhood onset HP patients. Genetic defects were identified in 27.7% of early‐onset HP patients, including four kinds of syndromic HP and one isolated HP. A total of 13 novel mutations were detected, which expands the mutation spectrum of hypoparathyroidism. © 2019 American Society for Bone and Mineral Research.
Metastasis-directed Therapy Without Androgen Deprivation Therapy in Solitary Oligorecurrent Prostate Cancer

Purpose: As controversy remains regarding the role of metastasis-directed therapy in patients with oligometastatic prostate cancer, we sought to characterize outcomes of metastasis-directed therapy without concomitant androgen deprivation therapy in the specific subset of patients with a solitary metastatic lesion on C-11 choline positron emission tomography imaging whose primary tumor has already been treated. Materials and Methods: We identified 124 consecutive prostate cancer patients from 2008 to 2018 with a solitary oligorecurrent metastatic lesion on positron emission tomography imaging who were treated with metastasis-directed therapy without androgen deprivation therapy from the Mayo Clinic C-11 choline registry. Metastasis-directed therapy consisted of either stereotactic body radiation therapy or surgical excision. Results: Of these 124 patients, 67 were treated with surgery (median follow-up 54 months) and 57 patients were treated with stereotactic body radiation therapy (median follow-up 53 months). Of patients treated with surgery, 80.5% had >50% decline in prostate specific antigen at first follow-up, and the 3-year radiographic progression-free survival was 29%. Median time to initiation of systemic therapy in this cohort was 18.5 months (interquartile range 8.4-44.7 months). Meanwhile, for patients treated with stereotactic body radiation therapy, 40.3% had >50% decline in prostate specific antigen at first follow-up, and the 3-year radiographic progression-free survival was 17%. Similarly, median time to initiation of systemic therapy was 17.8 months (interquartile range 7.1-42.3 months). Conclusions: This study represents the first reported series of metastasis-directed therapy without androgen deprivation therapy in patients with solitary oligorecurrent metastatic prostate cancer. These results suggest that metastasis-directed therapy without androgen deprivation therapy can delay initiation of systemic therapy and highlight the need for further prospective study for select patients with solitary metastatic recurrences of prostate cancer.
Integrating Clinical Ultrasound into Screening for Cystic Fibrosis Liver Disease: Approach with Caution and Optimism.

need to have ‘‘personal equipoise,’’ not favoring a positive outcome over a negative one (13). Studies need to be adequately powered and designed, so that a negative study is as scientifically sound as a positive one. Medical journals need to embrace negative or neutral studies just as much as the positive ones (14). Some progress on this topic has been made, for example with the American Journal of Gastroenterology recently dedicating an entire issue to studies that had no statistically significant superiority of one outcome over another (15). Finally, penalties probably need to be imposed to pharmaceutical companies who keep the less favorable results from being reported in medical journals.
IL-4 Augments IL-31/IL-31 Receptor Alpha Interaction Leading to Enhanced Ccl 17 and Ccl 22 Production in Dendritic Cells: Implications for Atopic Dermatitis

Severe pruritus is a characteristic feature of atopic dermatitis (AD) and is closely related to its activity. Recent studies have shown that IL-31 is a key determinant of pruritus in AD. Anti-IL-31 receptor alpha (IL-31RA) antibody treatment has also been reported to improve pruritus clinically, subsequently contributing to the attenuation of AD disease activity. Therefore, IL-31 has been thought to be an important cytokine for regulating pruritus and AD disease activity; however, how IL-31 is involved in the immune response in AD has remained largely unknown. Epidermal Langerhans cells (LCs) and dermal dendritic cells (DCs) derived from bone marrow cells have been reported to play a critical role in AD pathogenesis. LCs and DCs produce Ccl 17 and Ccl 22, which chemoattract Th2 cells, leading to AD development. Therefore, we aimed to clarify how IL-31/IL-31RA interaction affects Ccl 17 and Ccl 22 production. To test this, we analyzed murine bone marrow-derived DCs (BMDCs) stimulated with IL-4, an important cytokine in AD development. We found that IL-31RA expression was upregulated by IL-4 stimulation in a dose-dependent manner in BMDCs. Furthermore, IL-31 upregulates Ccl 17 and Ccl 22 production in the presence of IL-4, whereas IL-31 stimulation alone did not produce Ccl 17 and Ccl 22. These findings suggest that IL-4 mediates IL-31RA expression and IL-31/IL-31RA interaction augments Ccl 17 and Ccl 22 production in BMDCs, which promotes Th2-deviated immune response in AD. Since we previously reported that soybean tar Glyteer, an aryl hydrocarbon receptor (AHR) ligand, impairs IL-4/Stat 6 signaling in BMDCs, we examined whether Glyteer affects IL-31RA expression induced by IL-4 stimulation. Glyteer inhibited upregulation of IL-31RA expression induced by IL-4 stimulation in a dose-dependent manner. Glyteer also inhibited Ccl 17 and Ccl 22 production induced by IL-4 and IL-31 stimulation. Taken together, these findings suggest that Glyteer treatment may improve AD disease activity by impairing IL-31/IL-31RA interaction in DCs.
The Application of PRECEDE Model on Preventing Osteoporosis in Women

The aim of this study is investigating the efficiency of educational intervention based on PRECEDE model on promotion of osteoporosis prevention behaviors in women. This quasi-experimental study was conducted on 200 women registered in two health centers of Fasa city, Fars province, Iran in 2017 to 2018. A questionnaire including items evaluating demographic information and PRECEDE model constructs was used for measuring nutrition and walking performance of studied women in osteoporosis prevention before and 12 months after intervention. Bone mineral density (BMD) was recorded at the lumbar spine and femur before and 12 months after intervention. One year after intervention, the intervention group showed a significant increase in knowledge, attitude, self-efficacy, reinforcing factors, enabling factors, nutrition, and walking performance compared to the control group. Also, the value of lumbar spine and hip BMD T-Score of the intervention group was increased, while this value was reduced in the control group. Our findings showed that educational interventions based on PRECEDE model can positively affect prevention behaviors from osteoporosis by improving subjects’ knowledge, attitude, enabling factors (resources such as health care access and services that can provide motivation for prevention behaviors from osteoporosis in women), self-efficacy, and reinforcing factors.
Age, period and cohort effects in activities of daily living, physical and cognitive functioning impairment among the oldest-old in China.

BACKGROUND The aim of this study was to examine the trends in impairment regarding activities of daily living (ADL), physical performance and cognitive function among the oldest-old (those aged ≥80 years) in China between 1998 and 2014. METHODS We used data on 34,297 oldest-old individuals from the seven waves of the Chinese Longitudinal Healthy Longevity Study. We estimated age, period and cohort effects on the prevalence of self-reported ADL impairment, tested physical performance and cognitive function impairment using the age-period-cohort (APC) model. RESULTS Regarding age, the prevalence of ADL, physical and cognitive impairment were highest in the centenarians, but they did not increase with age in this population. Among the literate subgroup, the prevalence of cognitive impairment increased more rapidly with age than that in the illiterate subgroup. Regarding period, the prevalence of self-reported and tested physical impairment slowly increased between 1998 and 2014, but cognitive impairment remained stable. Regarding cohort, ADL impairment continuously decreased. However, physical and cognitive impairment remained stable after a brief decline in the early birth cohorts. CONCLUSIONS The results suggest that the age effect is still the most obvious effect regarding several types of functional impairment. The likelihood of a younger person experiencing functional impairment may not change significantly, but ADL is likely to be amenable to improvement resulting from improved medical and social care. Therefore, increased care for the elderly may considerably improve their quality of life, particularly regarding their basic activities of daily living.
A sensitive method for reliable quantification of sulfane sulfur in biological samples.

Sulfane sulfur has been recognized as a common cellular component, participating in regulating enzyme activities and signaling pathways. However, the quantification of total sulfane sulfur in biological samples is still a challenge. Here, we developed a method to address the need. All tested sulfane sulfur reacted with sulfite and quantitatively converted to thiosulfate when heated at 95oC in a solution of pH 9.5 for 10 min. The assay condition was also sufficient to convert total sulfane sulfur in biological samples to thiosulfate for further derivatization and quantification. We applied the method to detect sulfane sulfur contents at different growth phases of bacteria, yeast, mammalian cells, and zebrafish. Total sulfane sulfur contents in all of them increased in the early stage, kept at a steady state for a period and declined sharply in the late stage of the growth. Sulfane sulfur contents varied in different species. For Escherichia coli, growth media also affected the sulfane sulfur contents. Total sulfane sulfur contents from different organs of mouse and shrimp were also detected, varying from 1 to 10 nmol/mg protein. Thus, the new method is suitable for the quantification of total sulfane sulfur in biological samples.
Occupational Exposure to Solar UV Radiation of a Group of Fishermen Working in the Italian North Adriatic Sea

Occupational solar radiation exposure is a relevant heath risk in the fishing sector. Our aim was to provide a detailed evaluation of individual UV exposure in three different fishing activities in Italy, with personal UV dosimeters and a simple formula to calculate the fraction of ambient erythemal UV dose received by the workers. The potential individual UV exposure of the fishermen was between 65 and 542 Joules/m2. The percentages of the ambient exposure were estimated between 2.5% and 65.3%. Workers’ UV exposure was mainly influenced by the characteristics of the work activity, the postures adopted, and the type of boats. Overall, our data showed that 43% of the daily measurements could result largely above the occupational limits of 1–1.3 standard erythemal dose (i.e., 100 Joules/m2) per day, in case of exposure of uncovered skin areas. Measurements of individual UV exposure are important not only to assess the risk but also to increase workers’ perception and stimulate the adoption of preventive measures to reduce solar UV risk. Furthermore, the simple method proposed, linking ambient erythemal UV dose to the workers’ exposure, can be a promising tool for a reliable assessment of the UV risk, as time series of environmental UV dose are widely available.