Miracle-dz/UniFAR-FTUs huggingface dataset:
The efficacy and potential predictive factors of PD-1/PD-L1 blockades in epithelial carcinoma patients: a systematic review and meta analysis

Background This systematic analysis aims to assess the efficacy of PD-1/PD-L1 blockades compared with non-PD-1/PD-L1 therapy and investigate the potential predictive factors in epithelial carcinoma patients. Results A total of 11 trials with 6716 patients of melanoma, non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) were included. The pooled HRs (95%CI) were 0.67 (0.62, 0.73), p < 0.001 for OS and 0.66 (0.57, 0.76), p < 0.001 for PFS. In subgroup analyses, HRs were 0.58 (0.50, 0.66), p < 0.001 in PD-L1 ≥ 1% group, 0.75 (0.63, 0.89), p = 0.001 in PD-L1 < 1% group for OS and 0.59 (0.48, 0.72), p < 0.001 in PD-L1 ≥ 1% group, 0.80 (0.59, 1.07), p = 0.136 in PD-L1 < 1% group for PFS. The p values of pooled HRs for OS in different age, sex and ECOG score groups were less than 0.001. In NSCLC patients, aggregated HRs for OS were 1.40 (0.92, 2.12), p = 0.114 in EGFR mutant group and 0.88 (0.59, 1.32), p = 0.536 in never smokers. Methods A systematic search from January 2010 to April 2016 was conducted for eligible clinical trials. Based on the data of hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS), we assessed the pooled HRs and proposed the subgroup analyses. Conclusions PD-1/PD-L1 blockades prolonged OS and PFS in epithelial carcinoma patients. PD-L1 expression was a predictive factor for PFS but not predictive for OS. Age, sex and ECOG score were excluded to predict any of the efficacy endpoints. Smoking history and EGFR wild type were associated with extended OS in NSCLC patients.
THE DETECTION OF APPROPRIATE ORGANIC FERTILIZER AND MYCORRHIZAL METHOD ENHANCING SALT STRESS TOLERANCE IN RICE (Oryza sativa L.) UNDER FIELD CONDITIONS

This study was performed in order to identify the appropriate organic fertilizer and mycorrhizal methods for promoting rice tolerance in response to salty environmental conditions. For this purpose, some agronomic, biochemical and physiological parameters were investigated in rice under natural salt stress. The plants were grown in saline field conditions from germination to harvest stage and fertilizing consisted of only a mixture of different ratios of mycorrhizal, municipal solid waste (MSW), waste tea leaves, straw, olive manure and chicken manure. Samples of the plants were taken when they reached harvesting stage and their agronomical properties (plant height, number of leaves, leaf sheaths length, tillering, leaf area, panicle length, total and milled rice values and 1000 grain weight) were recorded and biochemical (chlorophyll a and b) and physiological analysis (Na, K, Ca, Si amounts in roots) were performed. The results showed that improvements in vegetative characters except leaf number were obtained with trials with MSW, MSW+waste tea leaves+straw or MSW+waste tea leaves+straw+chicken or olive manure including fertilizers, increase in chlorophyll b content was obtained with trials except with mycorrhiza, and decreased root Na levels and increases in chlorophyll a content (biochemical parameter) were obtained particularly with trials with of the mycorrhiza+MSW pair or mycorrhiza+MSW+waste tea leave mixture. The best fertilizing mixture, straw (100kg/decare) + MSW (75g / 2,5m 2 ), was in experiment no: 2. Additionally, there was no change in the low yield; but certain additives were necessary. In conclusion, organic waste and mycorrhizal fertilizer applications with specific ratios were determined to have a protective effect on plants against salt stress.
Some observations on the definition and estimation of effect sizes

General considerations Many valuable comments have been made by contributors and while some of the key issues have been aired, I would like to suggest that prior to considering effect sizes it is important to pay attention to the correct specification of the statistical model being used. Thus, for standard regression or multilevel models the assumption of Normality is typically made and much of the literature on effect sizes, especially that which concentrates on standardised effects, assumes Normality. A prior transformation to Normality, for example using Normal scores, may often be needed, for both for the response and predictor distributions. Likewise, the existence of complexity in the form of interactions, or random coefficients in a multilevel model, should be explored and where such complexities exist a graphical presentation of effects will usually be especially helpful.
Views on Researcher-Community Engagement in Autism Research in the United Kingdom: A Mixed-Methods Study

There has been a substantial increase in research activity on autism during the past decade. Research into effective ways of responding to the immediate needs of autistic people is, however, less advanced, as are efforts at translating basic science research into service provision. Involving community members in research is one potential way of reducing this gap. This study therefore investigated the views of community involvement in autism research both from the perspectives of autism researchers and of community members, including autistic adults, family members and practitioners. Results from a large-scale questionnaire study (n = 1,516) showed that researchers perceive themselves to be engaged with the autism community but that community members, most notably autistic people and their families, did not share this view. Focus groups/interviews with 72 participants further identified the potential benefits and remaining challenges to involvement in research, especially regarding the distinct perspectives of different stakeholders. Researchers were skeptical about the possibilities of dramatically increasing community engagement, while community members themselves spoke about the challenges to fully understanding and influencing the research process. We suggest that the lack of a shared approach to community engagement in UK autism research represents a key roadblock to translational endeavors.
High-throughput typing

This study investigates aspects of the general assumption that, in bacteria, genetic variation in functionally-constrained genomic regions accumulates at a lower rate than in regions of hypermutability such as DNA repeat loci. We compared whole genome polymorphism (using high-throughput amplified fragment length polymorphism [ht-AFLP]) as well as short sequence repeat length variation (using multi-locus variable number of tandem repeat analysis [MLVA]) for 994 Staphylococcus aureus strains isolated from both healthy carriers and invasive infections. MLVA and ht-AFLP minimum spanning trees (MSTs) were similar in their identification of totally different types of genetic variants. This suggests that, despite the enhanced inherent variability of repeats, clusters of strains remain traceable. Finally, no specific molecular marker of epidemicity or virulence was identified in this large strain collection by the MLVA approach. We demonstrate that there is a difference in the rates of cross-genome mutation versus regional repeat variability in the clonal bacterial pathogen S. aureus. Despite these dynamic differences, a [. ] MELLES, D. C. , et al. High-throughput typing of Staphylococcus aureus by amplified fragment length polymorphism (AFLP) or multi-locus variable number of tandem repeat analysis (MLVA) reveals consistent strain relatedness. European Journal of Clinical Microbiology & Infectious Diseases, 2009, vol. 28, no. 1, p. 39-45 DOI : 10.1007/s10096-008-0585-4
[Infective endocarditis in patients with chronic liver disease: clinical and prognostic assessment].

INTRODUCTION AND OBJECTIVES Chronic liver disease increases the susceptibility to bacterial infections and infective endocarditis. Our aim was to determine the clinical and microbiological features and the prognosis in patients with chronic liver disease who also had infective endocarditis. PATIENTS AND METHOD One hundred and seventy-four consecutive inpatients at our institution were recruited and followed. Thirty of them had chronic liver disease. Clinical, microbiological and echocardiographic variables were analyzed and, in some cases, histological variables were also recorded. RESULTS Patients with chronic liver disease were younger (36 11 vs 54 18 years; p < 0.01) and had a larger proportion of intravenous drug users (73 vs 16%; p < 0.01), HIV infection (47 vs 10%; p < 0.01), right valve involvement and spleen enlargement, but heart failure appeared less often (7 vs 34%; p = 0.003). Thirty percent of the patients with and 51% of patients without chronic liver disease underwent surgery for infective endocarditis. Total mortality among patients with and without chronic liver disease was 40% and 31%, respectively. After adjustment for age and for the incidence of congestive heart failure, chronic liver disease doubled mid-term mortality with a RR = 2.45 (p = 0.015). CONCLUSIONS Chronic liver disease has a significant impact on the prognosis in patients with infective endocarditis, and these patients should therefore be considered a high risk group.
Validation study of the Alzheimer’s disease assessment scale–cognitive subscale (ADAS-Cog) for the Portuguese patients with mild cognitive impairment and Alzheimer’s disease

Abstract Objective: The Alzheimer’s disease assessment scale–Cognitive Subscale (ADAS-Cog) is a battery to assess cognitive performance in Alzheimer’s disease (AD) and was developed according to the core characteristics of cognitive decline in AD: memory, language, praxis, constructive ability, and orientation. The aim of this study was to explore the diagnostic accuracy and discriminative capacity of the ADAS-Cog for Mild Cognitive Impairment (MCI) and AD, using cut-off points for the Portuguese population. Method: The European Portuguese version of the ADAS-Cog was administrated to 650 participants, divided into a control group (n = 210), an MCI group (n = 240), and an AD group (n = 200). The clinical groups fulfilled standard international diagnostic criteria. Controls were healthy cognitive participants actively integrated in the community. The neuropsychological assessment protocol included the ADAS-Cog, the Mini Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), and the Adults and Older Adults Functional Assessment Inventory (IAFAI). Results: The ADAS-Cog revealed good psychometric indicators, and the total scores were significantly different between the three groups (p < .001: Control < MCI < AD). The optimal cut-off points established were: MCI > 9 points (AUC = .835; sensitivity = 58% and specificity = 91%) and AD > 12 points (AUC = .996; sensitivity = 94% and specificity = 98%). Conclusions: Our findings confirmed the capacity of the ADAS-Cog total score to identify cognitive impairment in AD patients, with poor sensitivity for MCI, in a Portuguese cohort.
In situ organic compound analysis on a meteorite surface by desorption electrospray ionization coupled with an Orbitrap mass spectrometer.

RATIONALE Since extraterrestrial organic matter in meteorites is a very complex mixture that is hard to ionize due to its association with minerals, in situ analysis of polar organic compounds has never been performed. In addition, when studying powdered samples, spatial information of organic compounds is lost. METHODS In situ molecular analysis and chemical imaging of polar organic compounds were performed on a meteorite surface by desorption electrospray ionization coupled with high-resolution mass spectrometry (DESI-HRMS) using an Orbitrap mass spectrometer. RESULTS Many CHN compounds, including alkylated pyridine and imidazole homologues, were identified from the complex peaks by HRMS using a spray of electrically charged methanol with a spatial resolution of approximately 50 μm. The same alkylated homologues have the same spatial distribution in the meteorite matrix, while alkylpyridines occur in a different location from alkylimidazoles. CONCLUSIONS The compound distribution suggests a different source for each compound series or a chromatographic separation effect associated with fluid movement in the meteorite parent body. The DESI-HRMS imaging will further our understanding of organic compound distribution with respect to mineral and water interactions in meteorites.
Reducing Channel Interaction Through Cochlear Implant Programming May Improve Speech Perception

Speech perception among cochlear implant (CI) listeners is highly variable. High degrees of channel interaction are associated with poorer speech understanding. Two methods for reducing channel interaction, focusing electrical fields, and deactivating subsets of channels were assessed by the change in vowel and consonant identification scores with different program settings. The main hypotheses were that (a) focused stimulation will improve phoneme recognition and (b) speech perception will improve when channels with high thresholds are deactivated. To select high-threshold channels for deactivation, subjects’ threshold profiles were processed to enhance the peaks and troughs, and then an exclusion or inclusion criterion based on the mean and standard deviation was used. Low-threshold channels were selected manually and matched in number and apex-to-base distribution. Nine ears in eight adult CI listeners with Advanced Bionics HiRes90k devices were tested with six experimental programs. Two, all-channel programs, (a) 14-channel partial tripolar (pTP) and (b) 14-channel monopolar (MP), and four variable-channel programs, derived from these two base programs, (c) pTP with high- and (d) low-threshold channels deactivated, and (e) MP with high- and (f) low-threshold channels deactivated, were created. Across subjects, performance was similar with pTP and MP programs. However, poorer performing subjects (scoring < 62% correct on vowel identification) tended to perform better with the all-channel pTP than with the MP program (1 > 2). These same subjects showed slightly more benefit with the reduced channel MP programs (5 and 6). Subjective ratings were consistent with performance. These finding suggest that reducing channel interaction may benefit poorer performing CI listeners.
Synaptic transmission in neurological disorders dissected by a quantitative approach

Synaptic transmission depends on several molecular and geometric components, such as the location of vesicular release, the number of released neurotransmitter molecules, the number and type of receptors, as well as the synapse organization. Our goal here is to illustrate how synaptic modeling allows extracting quantitative information in the context of neurological diseases and associated therapies. Combining electrophysiology with simulation tools, we first evaluate the reduction in synaptically released glutamate molecules induced by a ketogenic diet. In a second part, because the scaffolding molecule Shank3 is disrupted at the postsynaptic density in Autism Spectral Disorders, we present a numerical simulation of the synaptic response where this disruption leads to an alteration of the excitatory AMPA receptor trafficking. The take home message is that combining recent experimental findings with modeling approaches allows obtaining precise quantitative properties of what was still unapproachable a decade ago.
Reduction of Electrical Defects in Atomic Layer Deposited HfO2 Films by Al Doping

The gate leakage current density (Jg) of ultrathin (∼3 nm) Al-doped HfO2 (Al:HfO2) films with an Al concentration of ∼11% was lower than that of the control HfO2 film by 2 orders of magnitude at an equivalent oxide thickness of ∼1 nm. The permittivity of the Al:HfO2 film was similar to that of the control HfO2 film. Al doping of HfO2 films reduced the concentration of the oxygen vacancies and carbon in the film, which act as electrical defects (traps). It also increased the band gap of the film, resulting in a reduced Jg. Although the crystalline structure of a ∼ 12 nm-thick Al:HfO2 film contained both tetragonal and monoclinic phases after high temperature annealing, the ∼3 nm thick Al:HfO2 film showed a monoclinic structure, which is the same as the control HfO2 film. Therefore, there was no modification of the crystalline structure of the Al:HfO2 film in the ultrathin film case that would increase the permittivity. However, Si diffusion into the film and interfacial layer growth during annealing were s.
Predictive risk factors of failed laryngeal mask airway insertion at first attempt

Objectives A failed first attempt at laryngeal mask airway (LMA) insertion could increase the risk of laryngospasm, hypoxemia, and postoperative sore throat. This study was performed to investigate the risk factors for failed first-attempt LMA placement. Methods In total, 461 patients who underwent general anesthesia with a Supreme LMA (Teleflex Medical, Shanghai, China) and who had an American Society of Anesthesiologists (ASA) physical status of I to III were prospectively enrolled. The LMA was inserted after anesthetic induction. We recorded the insertion conditions and each patient’s age, ASA status, body weight, body mass index (BMI), duration of anesthesia, size of LMA, and cuff pressure; the years of work experience of the anesthesiologists; and the use or nonuse of lidocaine gel as a lubricant. Results Successful first-attempt placement of the Supreme LMA was achieved in 438 (95.10%) patients, while first-attempt placement failed in 23 (4.99%). Significant risk factors for failure of first-attempt LMA insertion included high age, high body weight, BMI of <20 kg/m2, and insertion without using lidocaine gel. Conclusions A patient age of >61 years, high body weight, BMI of <20 kg/m2, and insertion without lidocaine gel could significantly increase the risk of failed first-attempt Supreme LMA insertion.
Crystal structure of Mycobacterium tuberculosis VapC20 toxin and its interactions with cognate antitoxin, VapB20, suggest a model for toxin–antitoxin assembly

VapBCs, virulence‐associated proteins, are the most abundant type II toxin–antitoxin (TA) systems in prokaryotes. Under normal conditions, toxin and antitoxin interact to form a heterooctameric complex, which upon binding to operator sites, inhibits their own expression. Under stress conditions, the VapB antitoxin is degraded by cellular proteases to release a free VapC toxin, which in turn inhibits cell growth mainly by targeting protein translation. However, the intermediate steps involved in the assembly of the heterooctameric complex have not been resolved. Here, we report a 1.75 Å resolution crystal structure of VapC20, a Sarcin‐Ricin loop cleaving toxin from type II TA system of Mycobacterium tuberculosis. Using analytical ultracentrifugation (AUC) studies, we show that VapC20 exists as a homodimer in solution. The structural analysis of VapC homologs further suggests that VapCs form homodimers. We demonstrate that VapC20 is an obligate homodimer, and its self‐association is critical for its folding and activity. Surface plasmon resonance experiments suggest that VapC20 interacts with its cognate antitoxin VapB20 to form a stable complex with nanomolar affinity. A high association rate coupled with a very slow dissociation rate ensures minimal toxicity under normal growth conditions. AUC studies reveal that VapB20 also exists as a homodimer in solution and further associates with VapC20 dimers to form heterotetramers and heterooctamers in a concentration‐dependent manner. The results presented here provide valuable insights into the assembly of VapBC family of toxins which is essential for their function and regulation.
Main phases of wood formation in chestnut (Castanea sativa) in Central Italy: comparison of seasons 2008 and 2009

Rad obrađuje stvaranje drva pitomog kestena (Castanea sativa) tijekom vegetacije u 2008. i 2009. godini. Uspoređuje se dinamika stvaranja drva u te dvije godine i raspravlja o mogucem utjecaju na njegovu kvalitetu. Za tu su svrhu s deset stabala pitomog kestena u planinama Cimini, pokraj mjesta Viterbo u sredisnjoj Italiji, u tjednim intervalima skupljeni mikroizvrtci koji su sadržavali drvo, kambij i fl oem. Pocetak stvaranja drva u 2008. godini dogodio se prije uzimanja prvih uzoraka 17. travnja 2008. Pocetak lignifi kacije prvooblikovanih traheja primijecen je oko 23. travnja (dan u godini DOY 113,8 ± 5,3), a prve traheje kasnog drva primijecene su oko 5. lipnja (DOY 156,5 ± 7,7). Stvaranje kasnog drva nastavljeno je do 29. rujna 2008. (DOY 273,9 ± 10,5), kad su zavrsne stanice novostvorenoga goda drva bile potpuno lignifi cirane. U 2009. godini glavne su se faze stvaranja drva uglavnom pojavile ranije nego u 2008. godini. Sirenje traheja ranog drva primijeceno je oko 10. travnja (DOY 99,7 ± 6,1), pocetak lignifi kacije oko 22. travnja (DOY 111,9 ± 7,4), a prve traheje kasnog drva oko 28. svibnja 2009. (DOY 147,9 ± 4,7). Lignifi kacija zadnjih proizvedenih stanica zavrsena je do 26. rujna 2009. (DOY 273,9 ± 10,5). Prosjecno trajanje stvaranja goda drva u 2008. godini iznosilo je 161 dan, a u 2009. godini 169 dana. Prosjecne sirine godova bile su 3296 ± 1514 μm u 2008. godini i 3166 ± 1073 μm u 2009. godini, a postotni udjel kasnog drva iznosio je 76 i 74% godova u 2008. , odnosno u 2009. godini. Male razlike u vremenu pocetka pojedine faza stvaranja drva u dvjema promatranim godinama vjerojatno su posljedica malih varijacija klimatskih uvjeta između te dvije godine i cini se da nemaju velik utjecaj na sirinu godova ni na postotak kasnog drva, a to su dva važna cimbenika koji utjecu na kvalitetu drva prstenasto poroznih vrsta.
High-Q silica microdisk optical resonators with large wedge angles on a silicon chip

We experimentally demonstrate high optical quality factor silica microdisk resonators on a silicon chip with large wedge angles by reactive ion etching. For 2-μm-thick microresonators, we have achieved wedge angles of 59°, 63°, 70°, and 79° with optical quality factors of 2.4×107, 8.1×106, 5.9×106, and 7.4×106, respectively, from ∼80 μm-diameter microresonators in the 1550 nm wavelength band. Also, for 1-μm-thick microresonators, we have obtained an optical quality factor of 7.3×106 with a wedge angle of 74°.