Miracle-dz/UniFAR-FTUs huggingface dataset:
Zinc carnosine-based modified bismuth quadruple therapy vs standard triple therapy for Helicobacter pylori eradication: A randomized controlled study

BACKGROUND Helicobacter pylori (H. pylori) infection is a worldwide problem with increasing burden on the health sector due to its increasing rate of resistance. The conventional triple therapy (TT) is becoming obsolete with a high failure rate of eradication, necessitating the need for better alternatives or regimens. AIM To investigate H. pylori eradication rate of TT vs modified bismuth quadruple therapy. METHODS Ninety-two patients with dyspepsia symptoms and positive 13C-urea breath test were randomly assigned to two groups. The first group (control group) was treated for 14 d using standard TT protocol: Esomeprazole (40 mg twice daily), amoxicillin (1 g twice daily) and clarithromycin (500 mg twice daily). On the other hand, the second group was prescribed a 10-d course of modified bismuth quadruple therapy fortified with zinc carnosine: TT in addition to bismuth subcitrate (240 mg twice daily) and zinc carnosine (75 mg twice daily). A repeated 13C-urea breath test was done 4 wk after the completion of the eradication therapy. RESULTS Among the 92 subjects, 67.4% were males and 32.6% were females. There were no differences in demographic characteristics (age, body mass index, smoking history, previous antibiotics use and ethnicity) between the modified bismuth quadruple therapy group and TT group. The eradication rate was higher [93.5% (43/46)] in the modified bismuth quadruple therapy group compared to 69.6% (32/46) in the standard TT group (P = 0.003). Of the tested predictor variables, only nationality, smoking and therapy type were statistically significant. Besides dizziness, which was recorded in modified bismuth quadruple therapy group, there were no significant differences in side effects between the two groups. CONCLUSION Ten days of modified bismuth quadruple therapy fortified with zinc carnosine is superior to 14 d of conventional TT in eradicating H. pylori infection, with no additional significant adverse events.
Functional CRISPR and shRNA Screens Identify Involvement of Mitochondrial Electron Transport in the Activation of Evofosfamide

Evofosfamide (TH-302) is a hypoxia-activated DNA-crosslinking prodrug currently in clinical development for cancer therapy. Oxygen-sensitive activation of evofosfamide depends on one-electron reduction, yet the reductases that catalyze this process in tumors are unknown. We used RNA sequencing, whole-genome CRISPR knockout, and reductase-focused short hairpin RNA screens to interrogate modifiers of evofosfamide activation in cancer cell lines. Involvement of mitochondrial electron transport in the activation of evofosfamide and the related nitroaromatic compounds EF5 and FSL-61 was investigated using 143B ρ0 (ρ zero) cells devoid of mitochondrial DNA and biochemical assays in UT-SCC-74B cells. The potency of evofosfamide in 30 genetically diverse cancer cell lines correlated with the expression of genes involved in mitochondrial electron transfer. A whole-genome CRISPR screen in KBM-7 cells identified the DNA damage-response factors SLX4IP, C10orf90 (FATS), and SLFN11, in addition to the key regulator of mitochondrial function, YME1L1, and several complex I constituents as modifiers of evofosfamide sensitivity. A reductase-focused shRNA screen in UT-SCC-74B cells similarly identified mitochondrial respiratory chain factors. Surprisingly, 143B ρ0 cells showed enhanced evofosfamide activation and sensitivity but had global transcriptional changes, including increased expression of nonmitochondrial flavoreductases. In UT-SCC-74B cells, evofosfamide oxidized cytochromes a, b, and c and inhibited respiration at complexes I, II, and IV without quenching reactive oxygen species production. Our results suggest that the mitochondrial electron transport chain contributes to evofosfamide activation and that predicting evofosfamide sensitivity in patients by measuring the expression of canonical bioreductive enzymes such as cytochrome P450 oxidoreductase is likely to be futile.
Performance evaluation of a whole-body prototype PET scanner with four-layer DOI detectors

Parallax error caused by the detector crystal thickness degrades spatial resolution at the peripheral regions of the field-of-view (FOV) of a scanner. To resolve this issue, depth-of-interaction (DOI) measurement is a promising solution to improve the spatial resolution and its uniformity over the entire FOV. Even though DOI detectors have been used in dedicated systems with a small ring diameter such as for the human brain, breast and small animals, the use of DOI detectors for a large bore whole-body PET system has not been demonstrated yet. We have developed a four-layered DOI detector, and its potential for a brain dedicated system has been proven in our previous development. In the present work, we investigated the use of the four-layer DOI detector for a large bore PET system by developing the world’s first whole-body prototype. We evaluated its performance characteristics in accordance with the NEMA NU 2 standard. Furthermore, the impact of incorporating DOI information was evaluated with the NEMA NU 4 image quality phantom. Point source images were reconstructed with a filtered back projection (FBP), and an average spatial resolution of 5.2 ± 0.7 mm was obtained. For the FBP image, the four-layer DOI information improved the radial spatial resolution by 48% at the 20 cm offset position. The peak noise-equivalent count rate (NECR) was 22.9 kcps at 7.4 kBq ml−1 and the scatter fraction was 44%. The system sensitivity was 5.9 kcps MBq−1. For the NEMA NU 2 image quality phantom, the 10 mm sphere was clearly visualized without any artifacts. For the NEMA NU 4 image quality phantom, we measured the phantom at 0, 10 and 20 cm offset positions. As a result, we found the image with four-layer DOI could visualize the 2 mm-diameter hot cylinder although it could not be recognized on the image without DOI. The average improvements in the recovery coefficients for the five hot rods (1–5 mm) were 0.3%, 4.4% and 26.3% at the 0, 10 and 20 cm offset positions, respectively (except for the 1 mm-diameter rod at the 20 cm offset position). Although several practical issues (such as adding end-shields) remain to be addressed before the scanner is ready for clinical use, we showed that the four-layer DOI technology provided higher and more uniform spatial resolution over the FOV and improved contrast for small uptake regions located at the peripheral FOV, which could improve detectability of small and distal lesions such as nodal metastases, especially in obese patients.
Prevalence and Correlates of Youth Suicidal Ideation and Attempts: Evidence from the 2014 Ontario Child Health Study

Objectives: To present the 12-month prevalence and correlates of suicidal ideation and attempts in a sample of youth in Ontario. Methods: Data come from the 2014 Ontario Child Health Study, a provincially representative survey of families with children in Ontario. Youth aged 14 to 17 y (n = 2,396) completed a computer-assisted, self-administered questionnaire in their home to assess the occurrence of suicidal ideation, suicidal attempts, and associated correlates, including non-suicidal self-injury, mental disorders, substance use, peer victimization and exposure to child maltreatment. Socio-demographic information was collected from the parent. Logistic regression models were used to identify correlates that distinguished between youth reporting: 1) no suicidal ideation or attempts, 2) suicidal ideation but no attempts, and 3) suicidal ideation and attempts. Results: The 12-month prevalence of suicidal ideation and attempts was 8.1% and 4.3%, respectively. All clinical and behavioural correlates were significantly higher among youth reporting suicidal ideation or attempts, as compared with non-suicidal youth. In adjusted models, depression and non-suicidal self-injury were each independently associated with elevated odds of suicidal ideation (OR = 4.84 and 4.19, respectively) and suicidal attempt (OR = 7.84 and 22.72, respectively). Among youth who reported suicidal ideation, the only variable that differentiated youth who attempted suicide v. those who did not, in adjusted models, was non-suicidal self-injury (OR = 3.89). Conclusions: Suicidal ideation and attempts are common among youth in Ontario, often co-occurring with mental disorders and high-risk behaviours. These findings underscore the need for effective prevention and intervention strategies, particularly for youth depression and non-suicidal self-injury.
Fifty‐two week follow‐up safety and effectiveness results of dupilumab treatment of moderate‐to‐severe atopic dermatitis from a retrospective, multicentric series

Atopic dermatitis (AD) is a chronic, systemic disease that has a multifactorial etiology, where immune system disorders and epidermal barrier dysfunction are added to the influence of genetic and environmental factors. Dupilumab has been approved by United States and the European Union regulatory agencies in 2017 for the treatment of moderate‐to‐severe AD in adult patients who are candidates for systemic treatment. In this short report, we present a retrospective, multicentric study, in which five hospitals in Andalusia, Spain, have taken part. Our objective is to evaluate the safety and effectiveness of dupilumab in patients with moderate‐to‐severe AD treated with dupilumab with at least 52 weeks of follow‐up.
Multimorbidity and Employment Outcomes Among Middle-Aged US Cancer Survivors

Cancer survivors with psychiatric multimorbidity are vulnerable to unemployment. Targeted treatment and employment supports may improve workforce participation after cancer. Abstract Objective The objective of this study was to evaluate the relationship between multimorbidity and subsequent 2-year employment outcomes among middle-aged United States (US) cancer survivors. In addition, we examined whether the relationship differed by survivor characteristics. Methods Data of 633 cancer survivors (ages 51 to 64) from the 2014 Health and Retirement Study were used to identify multimorbidity profiles and evaluate associations between multimorbidity and prolonged unemployment during follow-up. Results Approximately 64% of cancer survivors met the criteria for multimorbidity. Latent class analysis revealed three distinct multimorbidity profiles distinguished by the presence or absence of psychiatric disorders. We observed a significant association between high psychiatric multimorbidity and prolonged unemployment after 2-year follow-up (relative risk = 2.78, 95% Confidence Interval = 1.28 to 6.00), with the effect more pronounced among low-income survivors. Conclusions Psychiatric multimorbidity was associated with prolonged unemployment among middle-aged cancer survivors, particularly among low-income survivors.
Transmit-Array, Metasurface-Based Tunable Polarizer and High-Performance Biosensor in the Visible Regime

There are two types of metasurfaces, reflect-array and transmit-array,-which are classified on the basis of structural features. In this paper, we design a transmit-array metasurface for y-polarized incidence which is characterized by having a transmission spectrum with a narrow dip (i.e., less than 3 nm). Furthermore, a tunable polarizer is achieved using linear geometric configurations, realizing a transmittivity ratio between x- and y-polarized incidence ranging from 0.031% to 1%. Based on the narrow-band polarization sensitivity of our polarizer, a biosensor was designed to detect an environmental refractive index ranging from 1.30 to 1.39, with a factor of sensitivity S = 192 nm/RIU and figure of merit (FOM) = 64/RIU. In the case of a narrow-band feature and dips in transmission spectrums close to zero, FOM* can have a value as large as 92,333/RIU. This unique feature makes the novel transmit-array metasurface a potential market candidate in the field of biosensors. Moreover, transmit-array metasurfaces with lossless materials offer great convenience by means of detecting either the reflectance spectrum or the transmission spectrum.
Determining Self-Efficacy Perceptions of Pre-Service Turkish Language Teachers Towards Critical Reading

This study aims to reveal the self-efficacy perception levels of pre-service Turkish language teachers towards critical reading and to determine whether these levels vary by various variables. This study draws on a general survey model, which is one of the descriptive research methods. The study group of this research consists of a total of 210 freshman, sophomore, junior, and senior level pre-service Turkish language teachers studying at the Department of Turkish Language Education in the faculty of education at a state university. To collect data, “The Critical Reading Self-Efficacy Perception Scale” developed by Karabay (2013) is used. The findings of this study indicate that the self-efficacy perception levels of the pre-service Turkish language teachers towards critical reading are moderate. Furthermore, the pre-service Turkish language teachers’ self-efficacy perception levels towards critical reading do not significantly vary between the groups in the total score and in the sub-dimensions by variables of gender and academic achievement. Yet, there is a significant difference between the groups in the total score and in the sub-dimensions by variables of grade level and reading frequency. Based on these findings, this study also offers some insights and suggestions for researchers and teaching staff.
The impact of severe late-effects after 12 Gy fractionated total body irradiation and allogeneic stem cell transplantation for childhood leukemia (1988–2010)

Abstract This study consists of a retrospective study including 71 childhood leukemia survivors (36 females) treated with allo-HSCT 12 Gy fractionated total body irradiation (fTBI) conditioning, with a median age of 25.0 y at time of follow-up and a median delay of 14.8 y since the graft. The recovery ratio was 90%. The number of severe late-effects was specified for each patient: 21 with growth deficiency (final height <162.5 cm for 12/35 men and <152.0 cm for 9/36 women – Growth deficiency was correlated to young age at the time of the allograft); 5 with sclerodermic chronic graft vs. host disease; 9 with osteonecrosis; risk of impaired fertility for 25 women and 28 men (only 2 women had a child); 8 with diabetes; 5 with pulmonary late-effects including 1 death; 5 with chronic renal insufficiency including 1 death; 2 with cardiac late-effects; 2 with arterial high blood pressure; 11 (8 women) declared 14 subsequent cancers (7 with thyroid carcinomas, 3 with multiple squamous cell carcinomas, 2 with epidermoïdis carcinomas of the tongue or the lip, 1 with bone sarcoma, and 1 with carcinoma of the breast); 6 with chelating treatments of hemochromatosis; 14 with important educational underachievement; 11 with depression at adult age; 1 with hepatitis B virus infection; 4 with other severe late-effects, including 2 with blindness. The average number of severe late-effects was 2.3 with a positive correlation according to delay from fTBI (p < 0.0002). Two-thirds had at least 2 late-effects. These results emphasize the urgent abandonment of conditioning by TBI in children.
Influence of red grape pomace powder on physiochemical, antioxidant, nutritional, microbial, and sensory properties of probiotic yoghurt

: In this study, we investigated the effect of 2 and 4 % grape pomace powder (GPP) on the physiochemical, nutritional, microbial and sensory properties of probiotic yoghurt (contains Lactobacillus acidophilus and Bifidobacterium bifidum ) during the storage period every 7-day intervals (for 28 days). The results revealed that the pH, fat, protein, syneresis and sensory scores of samples decreased with elevation the grape pomace powder (GPP) level and also storage time. Ash, fiber, energy, total flavonoid, antioxidant activity, total phenol and the counting (log cfu/mL) of probiotic microorganisms decreased during storage, but the treatments with higher GPP had higher ash, fiber, energy, total flavonoid, antioxidant activity, total phenol content and probiotic counts. In converse, the acidity and viscosity increased with time storage and increase the GPP level. The probiotic yoghurt supplanted with 4% GPP in 0 day had the highest ash (1.2%), fiber (0.75%), energy (73.8 kcal/g), total flavonoid (4.9 mg Rutin equivalents/g) and antioxidant activity (42.4%). The highest viable count at the end of storage period (28 day) was obtained for probiotic yoghurt containing 4% GPP (8.03 log cfu/mL) and the lowest for control (6.2 log cfu/mL). Also the highest organoleptical scores belonged to yoghurt supplemented with 2% GPP at 0 day. The results of this research showed that grape pomace can be used in the production of probiotic yoghurt.
Effect of Red, Processed, and White Meat Consumption on the Risk of Gastric Cancer: An Overall and Dose–Response Meta-Analysis

Whether the risk of gastric cancer varies by the types of meat consumption still remains disputable. The purpose of this meta-analysis was to identify the exact associations that red, processed, and white meat have with gastric cancer. We searched relevant studies in Medline, EMBASE, and the Cochrane Library before November 2018, including cohort and case-control studies. We used random-effect models to estimate the adjusted relative risk (RR), and Egger’s tests to evaluate publication bias. Through stepwise screening, 43 studies were included in this analysis (11 cohort studies and 32 case-control studies with 16,572 cases). In a meta-analysis for the highest versus lowest categories of meat consumption, both red (RR: 1.41, 95% confidence interval (CI): 1.21–1.66) and processed (RR: 1.57, 95% CI: 1.37–1.81) meat consumption were positively associated with gastric cancer risk, while white meat consumption was negatively associated with gastric cancer risk (RR: 0.80, 95% CI: 0.69–0.92). In a dose–response meta-analysis, the RRs of gastric cancer were 1.26 (95% CI: 1.11–1.42) for every 100 g/day increment in red meat consumption, 1.72 (95% CI: 1.36–2.18) for every 50 g/day increment in processed meat consumption, and 0.86 (95% CI: 0.64–1.15) for every 100 g/day increment in white meat consumption. The increase of white meat consumption may reduce the risk of gastric cancer, while red or processed meat may increase the risk of gastric cancer. Further studies are required to identify these associations, especially between white meat and gastric cancer.
Deleterious somatic variants in 473 consecutive individuals with ovarian cancer: results of the observational AGO-TR1 study (NCT02222883)

Background For individuals with ovarian cancer (OC), therapy options mainly depend on BRCA1/2 germline status. What is the prevalence of deleterious somatic variants, that is, does genetic tumour testing identify subgroups of individuals who also might benefit from targeted therapy? Methods Paired analysis of tumour-derived versus blood-derived DNA to determine the prevalence of deleterious somatic variants in OC predisposition genes (ATM, BRCA1/2, BRIP1, MSH2/6, PALB2, RAD51C/D and TP53) and the PIK3CA and PTEN genes in individuals with OC (AGO-TR1 study, NCT02222883). Results were complemented by BRCA1, PALB2 and RAD51C promoter methylation analyses and stratified by histological subtype; 473 individuals were included. Results The combined analyses revealed that deleterious germline variants in established OC predisposition genes (all: 125/473, 26.4%; BRCA1/2: 97/473, 20.5%), deleterious somatic variants in established OC predisposition genes excluding TP53 (all: 39/473, 8.2%; BRCA1/2: 30/473, 6.3%) and promoter methylation (all: 67/473, 14.2%; BRCA1: 57/473, 12.1%; RAD51C: 10/473, 2.1%; PALB2: 0/473) were mutually exclusive, with a few exceptions. The same holds true for deleterious somatic PIK3CA and/or PTEN variants (33/473, 7.0%) found to be enriched in endometrioid and clear cell OC (16/35, 45.7%); 84.3 % of the deleterious single-nucleotide/indel germline variants in established OC predisposition genes showed significantly higher variant fractions (VFs) in the tumour-derived versus blood-derived DNA, indicating a loss of the wild-type alleles. Conclusion Tumour sequencing of the BRCA1, BRCA2, PIK3CA and PTEN genes along with BRCA1 and RAD51C promoter methylation analyses identified large subgroups of germline mutation-negative individuals who may be addressed in interventional studies using PARP or PI3K/AKT/mTOR inhibitors. Trial registration number NCT02222883
Paraventricular Thalamus Controls Behavior during Motivational Conflict

Decision-making often involves motivational conflict because of the competing demands of approach and avoidance for a common resource: behavior. This conflict must be resolved as a necessary precursor for adaptive behavior. Here we show a role for the paraventricular thalamus (PVT) in behavioral control during motivational conflict. We used Pavlovian counterconditioning in male rats to establish a conditioned stimulus (CS) as a signal for reward (or danger) and then transformed the same CS into a signal for danger (or reward). After such training, the CS controls conflicting appetitive and aversive behaviors. To assess PVT involvement in conflict, we injected an adeno-associated virus (AAV) expressing the genetically encoded Ca2+ indicator GCaMP and used fiber photometry to record population PVT Ca2+ signals. We show distinct profiles of responsivity across the anterior–posterior axis of PVT during conflict, including an ordinal relationship between posterior PVT CS responses and behavior strength. To study the causal role of PVT in behavioral control during conflict, we injected AAV expressing the inhibitory hM4Di DREADD and determined the effects of chemogenetic PVT inhibition on behavior. We show that chemogenetic inhibition across the anterior–posterior axis of the PVT, but not anterior or posterior PVT alone, disrupts arbitration between appetitive and aversive behaviors when they are in conflict but has no effect when these behaviors are assessed in isolation. Together, our findings identify PVT as central to behavioral control during motivational conflict. SIGNIFICANCE STATEMENT Animals, including humans, approach attractive stimuli and avoid aversive ones. However, they frequently face conflict when the demands of approach and avoidance are incompatible. Resolution of this conflict is fundamental to adaptive behavior. Here we show a role for the paraventricular thalamus, a nucleus of the dorsal midline thalamus, in the arbitration of appetitive and aversive behavior during motivational conflict.