Miracle-dz/UniFAR-FTUs huggingface dataset:
Acute kidney injury associated with immune checkpoint inhibitor therapy: incidence, risk factors and outcomes

Background Immune checkpoint inhibitors (ICPi) are a novel and promising anti-cancer therapy. There are limited data on the incidence, risk factors and outcomes of acute kidney injury (AKI) in patients receiving ICPi. Methods We conducted a cohort study of patients receiving ICPi at our center between 2010 and 2017 via electronic health record. The primary outcome was AKI (increase of >50% from baseline serum creatinine (sCr)). Risk factors for AKI were assessed using logistic regression. Survival among those with and without AKI was compared using the Kaplan-Meier method. Results Among 309 patients on ICPi, 51 (16.5%) developed AKI (Kidney Disease Improving Global Outcomes (KDIGO) stages 1: 53%, 2: 22%, 3: 25%). AKI was associated with other immune-related adverse events (IRAE) (OR 3.2, 95% CI 1.6 to 6; p<0.001), hypertension (OR 4.3, 95% CI 1.8 to 6.1; p<0.001) and cerebrovascular disease (OR 9.2; 95% CI 2.1 to 40; p<0.001). Baseline sCr, cancer, and ICPi type was not associated with AKI. Use of angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (OR 2.9; 95% CI 1.5 to 5.7; p=0.002), diuretics (OR 4.3; 95% CI 1.9 to 9.8; p<0.001), and corticosteroid treatment (OR 1.9; 95% CI 1.1 to 3.6; p=0.03) were associated with AKI. In the multivariable analysis, AKI was associated only with other IRAE (OR 2.82; 95% CI 1.45 to 5.48; p=0.002) and hypertension (OR 2.96; 95% CI 1.33 to 6.59; p=0.008). AKI was not associated with increased risk of mortality (HR 1.1; 95% CI: 0.8 to 1.6; p=0.67). ICPi nephrotoxicity was attributed via biopsy or nephrologist assessment in 12 patients (six interstitial nephritis, two membranous nephropathy, two minimal change disease, and two thrombotic microangiopathy). Subsequent doses of ICPi were administered to 12 patients with prior AKI, with one (8.3%) having recurrent AKI. Conclusion AKI is a common complication in patients receiving ICPi treatment. The development of other IRAE and previous diagnosis of hypertension were associated with increased AKI risk. AKI was not associated with worse survival. Distinguishing kidney IRAE from other causes of AKI will present a frequent challenge to oncology and nephrology practitioners. Kidney biopsy should be considered to characterize kidney lesions and guide potential therapy.
Development of New Therapeutics to Meet the Current Challenge of Drug Resistant Tuberculosis.

Tuberculosis (TB) is a prominent infective disease and a major reason of mortality/morbidity globally. Mycobacterium tuberculosis causes a long-lasting latent infection in a significant proportion of human population. The increasing burden of tuberculosis is mainly caused due to drug and multi drug-resistant. The failure of conventional treatment has been observed in large number of cases. Drugs that are used to treat extensively drug-resistant tuberculosis are expensive, have limited efficacy and with more side effects for longer duration of time and is often associated with poor prognosis. To regulate the emergence of multidrug resistant tuberculosis, extensively drug-resistant tuberculosis and totally drug resistant" tuberculosis, efforts are being made to understand the genetic/molecular basis of target drug delivery and mechanisms of drug resistance. Understanding the molecular approaches and pathology of Mycobacterium tuberculosis through whole genome sequencing may further help for the improvement of new therapeutics to meet the current challenge of global health. Understanding cellular mechanisms that trigger resistance to Mycobacterium tuberculosis infection may expose immune associates of protection which could be an important way for vaccine development, diagnostics and novel host-directed therapeutic strategies. Recent development of new drugs and combinational therapies for drugresistant tuberculosis through major collaboration between industry, donors and academia gives an improved hope to overcome the challenges in tuberculosis treatment. In this review article, we will try to high-light the new developments of drug resistance to the conventional drugs and the recent progress in the development of new therapeutics for the treatment of drug resistant and non-resistant cases.
Hrushovski's Encoding and ω-Categorical CSP Monsters

We produce a class of ω -categorical structures with ﬁnite signature by applying a model-theoretic construction – a reﬁnement of an encoding due to Hrushosvki – to ω -categorical structures in a possibly inﬁnite signature. We show that the encoded structures retain desirable algebraic properties of the original structures, but that the constraint satisfaction problems (CSPs) associated with these structures can be badly behaved in terms of computational complexity. This method allows us to systematically generate ω -categorical templates whose CSPs are complete for a variety of complexity classes of arbitrarily high complexity, and ω -categorical templates that show that membership in any given complexity class cannot be expressed by a set of identities on the polymorphisms. It moreover enables us to prove that recent results about the relevance of topology on polymorphism clones of ω -categorical structures also apply for CSP templates, i.e., structures in a ﬁnite language. Finally, we obtain a concrete algebraic criterion which could constitute a description of the delineation between tractability and NP-hardness in the dichotomy conjecture for ﬁrst-order reducts of ﬁnitely bounded homogeneous structures.
Association of prestroke metformin use, stroke severity, and thrombolysis outcome

Objective To evaluate whether pretreatment with metformin (MET) is associated with less stroke severity and better outcome after IV thrombolysis (IVT), we analyzed a cohort of 1,919 patients with stroke with type 2 diabetes mellitus in a multicenter exploratory analysis. Methods Data from patients with diabetes and ischemic stroke treated with IVT were collected within the European Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration. We applied propensity score matching (PSM) to obtain balanced baseline characteristics of patients treated with and without MET. Results Of 1,919 patients with stroke with type 2 diabetes who underwent IVT, 757 (39%) had received MET before stroke (MET+), whereas 1,162 (61%) had not (MET−). MET+ patients were younger with a male preponderance. Hypercholesterolemia and pretreatment with statins, antiplatelets, or antihypertensives were more common in the MET+ group. After PSM, the 2 groups were well balanced with respect to demographic and clinical aspects. Stroke severity on admission (NIH Stroke Scale 10.0 ± 6.7 vs 11.3 ± 6.5), 3-month degree of independence on modified Rankin Scale (2 [interquartile range (IQR) 1.0–4.0] vs 3 [IQR 1.0–4.0]), as well as mortality (12.5% vs 18%) were significantly lower in the MET+ group. The frequency of symptomatic intracerebral hemorrhages did not differ between groups. HbA1c levels were well-balanced between the groups. Conclusions Patients with stroke and diabetes on treatment with MET receiving IVT had less severe strokes on admission and a better functional outcome at 3 months. This suggests a protective effect of MET resulting in less severe strokes as well as beneficial thrombolysis outcome.
Effects of Single and Repeated Doses on Disposition and Kinetics of Doxycycline Hyclate in Goats

Simple Summary Doxycycline is used to treat bacterial infections such as pneumonia, skin and soft tissue infections, urinary tract infections, salmonellosis, and colibacillosis in goats. In goats, the single intravenous and intramuscular pharmacokinetics of doxycycline are known. However, there is no information regarding oral pharmacokinetics. This study aims to determine the single and repeated pharmacokinetics, bioavailability, and accumulation of doxycycline hyclate. Although doxycycline hyclate exhibited low intramuscular and oral bioavailability, its oral administration with favorable properties such as weak accumulation, wide distribution volume and long elimination half-life can be useful in the treatment of infections caused by susceptible pathogens in goats. Abstract The aims of this study in goats were to determine the pharmacokinetics of doxycycline hyclate following single intravenous (IV), intramuscular (IM) and oral administrations of 20 mg/kg and to evaluate the pharmacokinetics and accumulation of doxycycline hyclate after repeated oral administrations at a 20 mg/kg dose every 24 h for 5 days. Six healthy male goats were used for the study. The study was performed in four periods according to a longitudinal study with a 15-day washout period. Plasma concentrations of doxycycline were determined using HPLC-UV and analyzed by a non-compartmental method. IM injection of doxycycline caused swelling and pain due to irritation in the injection site. After IM and oral administrations, terminal elimination half-life (t1/2λz) and mean residence time (MRT) were prolonged and areas under the curve (AUCs) were low. The mean bioavailability of IM and oral administration was 51.51% and 31.39%, respectively. Following repeated oral administration, the accumulation ratio of doxycycline was 1.76. Pharmacokinetic properties including weak accumulation, wide distribution volume and long elimination half-life can make doxycycline hyclate valuable for repeated use via an oral route in the treatment of some infectious diseases in goats. However, the determination of pharmacodynamic effects on susceptible pathogens isolated from goats is also necessary to confirm the drug dosage regimen.
Lychee Pollination by the Honeybee

Pollination of lychee (Litchi chinensis Sonn.) by the honeybee was studied in Israel's two commercial cultivars, 'Mauritius' and 'Floridian'. Pollination rate, which was determined in a mixed 'Mauritius' and 'Floridian' plot, followed a consistent pattern: it was low at the first male (M,) 'Mauritius' bloom and reached a high value only when the pseudohermaphroditic (M2) 'Mauritius' bloom started. Pollen density on bees collected from 'Mauritius' inflorescences was very low during the M, bloom and increased to very high values during the M 2 bloom. These results indicate that the 'Mauritius' M, bloom does not play an important role as a source of pollen for pollination. Pronounced, significant, and consistent differences in nectar volume per flower and sugar concentration in the nectar were found between M 1, M2, and female (F) 'Mauritius' flowers. Values were very high in F flowers, medium in M 2 flowers, and low in M, flowers. Accordingly, the density of bees found on inflorescences was high during the F bloom, intermediate during the M 2 bloom, and low during the M1 bloom. The positive correlation between bee density and sugar concentration in the nectar was highly significant for M2 and F 'Mauritius' flowers. The nectar contained three sugars: glucose (43%), fructose (39%), and sucrose (18 %). This ratio was the same in nectar from M 1, M2, and F 'Mauritius' flowers. The lychee, which originated in China, was introduced to Israel in the 1930s. Only two cultivars have been planted commercially: 'Mauritius', introduced from South Africa, and 'Floridian', intro- duced from the U.S. The latter is probably a seedling of cv. Brewster (Degani et al., 1995b). Low productivity of the commer- cial lychee orchards in Israel prompted a study of its pollination. Lychee flowering in Israel occurs in late spring and lasts for about a month. Three distinct flowering waves can usually be observed in every in florescence. Each wave consists of flowers of the same type: the first wave consists of male flowers (M 1), the
Monitoring Species of Concern Using Noninvasive Genetic Sampling and Capture- Recapture Methods: Pilot Demonstration Wi th Coyote, a Predator to Species at Risk and Game Species on DoD Lands

Abstract : Through this project we demonstrated the effectiveness of an approach utilizing noninvasive genetic sampling combined with capture-recapture methods (NGS-CR) to evaluate the status of kit fox (Vulpes macrotis) populations on Dugway Proving Ground (DPG) and Sonoran pronghorn (Antilocapra americana sonoriensis) on the Barry M. Goldwater Range (BMGR). We compared the reliability of demographic parameters and the cost-efficiency of NGS-CR approaches with alternative approaches. We developed a spatio-temporal sampling design for acquiring noninvasive genetic data (via fecal scats) from individuals, genotyped samples for individual identification, analyzed genotypes with capture-recapture methods to obtain estimates of key population parameters, and developed a protocol for long-term monitoring in the future. We also quantified expenditures to examine cost efficiency of the approach. For both species, we concluded the NGS-CR method provided reliable estimates, improved monitoring (i.e., increased the number of demographic parameters estimates), and improved monitoring efficiency. Survey results indicated managers and technicians NGS-CR methods were easier to implement than traditional methods (e.g., radio telemetry). Managers at these installations have expressed interest in continuing using these NGS-CR methods.
Working with families: A systematic scoping review of family-centred care in universal, community-based maternal, child, and family health services

Children’s long- and short-term health and developmental outcomes can be improved when families are engaged and supported, and inform care planning. Family-centred care (FCC) underpins policy directions for universal, community-based, child and family health services in the early years, although its implementation in this context is poorly understood. This systematic scoping review of the current literature aimed to improve understanding of FCC implementation in maternal, child, and family health universal services. Key databases and grey literature were searched using descriptors of maternal, child, and family health population and context, and FCC concept. Reference checking identified further literature for analysis. Thirteen included papers reported on nine studies from Australia, New Zealand, and the United Kingdom. Limited participant representation of fathers and diverse community members was evident. Deductive thematic analysis identified four areas of FCC demonstrated in this literature: respectful relationships, effective communication to foster shared understanding, flexible and contextualized care, and support for autonomy and agency. The literature demonstrated the interplay between organizational, professional, and recipient factors and their impact on the implementation of FCC. For successful FCC implementation, all these elements should be considered.
In-Silico Analysis and Protective Efficacy of the PcrV Recombinant Vaccine against Pseudomonas Aeruginosa in the Burned and PA-Infected BALB/c Mouse Model.

BACKGROUND Pseudomonas aeruginosa is considered as the most severe cause of infections in burn patients and pneumonia infections. OBJECTIVE To study the protective effects of recombinant protein vaccine harboring the PcrV of P. aeruginosa in the mouse model of burn and respiratory infections. METHODS Recombinant protein vaccine harboring the PcrV was expressed in the E. coli BL-21 strain. Mice were immunized with the purified recombinant protein, and the antibody titer was measured in the sera obtained from the immunized mice. Immunized and control mice were challenged by active and passive immunization. The microbial counts in the lung, skin, liver, spleen, and kidney were compared with the control mice. RESULTS Bioinformatics analysis indicated that the PcrV protein was conserved in 1552 clinical and environmental isolates. Also, the isoelectric point (pI), molecular weight, and Grand Average of Hydropathy (GRAVY) score were analyzed. Mice were injected with recombinant protein, and serum from immunized mice reacted strongly with recombinant antigen at a dilution of 1:64000. The survival rate of mice infected with 5xLD50 of the P. aeruginosa increased significantly up to 75% in the standard strains (PAO1 and PAK), and the number of bacteria, especially in the internal organs (kidney, spleen, and liver) significantly reduced compared to the mice immunized with placebo. CONCLUSION Our results demonstrated that the PcrV protein could be an effective candidate vaccine for the generation of antibody response against P. aeruginosa infection.
Population Pharmacokinetics and Exposure–Response of Luspatercept, an Erythroid Maturation Agent, in Anemic Patients With Myelodysplastic Syndromes

Luspatercept is a recombinant fusion protein that enhances late‐stage erythroid maturation. This report describes the population pharmacokinetics and exposure–response relationship of luspatercept in 260 patients with anemia due to myelodysplastic syndromes. Luspatercept displayed linear and time‐invariant pharmacokinetics over a dose range of 0.125–1.75 mg/kg administered subcutaneously once every 3 weeks. Body weight was the only clinically relevant covariate of luspatercept exposure, supporting the weight‐based dosing. The probability of achieving transfusion independence ≥ 8 weeks increased with time‐averaged luspatercept serum exposure, reaching the plateau at doses 1.0–1.75 mg/kg. The probability of achieving multiple efficacy end points increased with slower luspatercept clearance, independent of effects of luspatercept exposure or disease characteristics. The probability of experiencing severe treatment‐emergent adverse events decreased with increasing luspatercept exposure, especially during long‐term treatment. These results provide a positive benefit–risk profile for the titration‐to‐response dose regimen (1.0–1.75 mg/kg) recommended for this population.
Productivity and water use efficiency of Agave americana in the first field trial as bioenergy feedstock on arid lands

Agave species are high‐yielding crassulacean acid metabolism (CAM) plants, some of which are grown commercially and recognized as potential bioenergy species for dry regions of the world. This study is the first field trial of Agave species for bioenergy in the United States, and was established to compare the production of Agave americana with the production of Agave tequilana and Agave fourcroydes, which are produced commercially in Mexico for tequila and fiber. The field trial included four experimental irrigation levels to test the response of biomass production to water inputs. After 3 years, annual production of healthy A. americana plants reached 9.3 Mg dry mass ha−1 yr−1 (including pup mass) with 530 mm of annual water inputs, including both rainfall and irrigation. Yields in the most arid conditions tested (300 mm yr−1 water input) were 2.0–4.0 Mg dry mass ha−1 yr−1. Agave tequilana and Agave fourcroydes were severely damaged by cold in the first winter, and produced maximum yields of only 0.04 Mg ha−1 yr−1 and 0.26 Mg ha−1 yr−1, respectively. The agave snout weevil (Scyphophorus acupunctatus) emerged as an important challenge for A. americana cropping, killing a greater number of plants in the higher irrigation treatments. Physiological differences in A. americana plants across irrigation treatments were most evident in the warmest season, with gas exchange beginning up to 3 h earlier and water use efficiency declining in treatments with the greatest water input (780 mm yr−1 water input). Yields were lower than previous projections for Agave species, but results from this study suggest that A. americana has potential as a bioenergy crop and would have substantially reduced irrigation requirements relative to conventional crops in the southwestern USA. Challenges for pest management and harvesting must still be addressed before an efficient production system that uses Agave can be realized.
A UNIFIED APPROACH TO ANALYZING NEST SUCCESS

Abstract Logistic regression has become increasingly popular for modeling nest success in terms of nest-specific explanatory variables. However, logistic regression models for nest fate are inappropriate when applied to data from nests found at various ages, for the same reason that the apparent estimator of nest success is biased (i.e. older clutches are more likely to be successful than younger clutches). A generalized linear model is presented and illustrated that gives ornithologists access to a flexible, suitable alternative to logistic regression that is appropriate when exposure periods vary, as they usually do. Unlike the Mayfield method (1961, 1975) and the logistic regression method of Aebischer (1999), the logistic-exposure model requires no assumptions about when nest losses occur. Nest survival models involving continuous and categorical explanatory variables, multiway classifications, and time-specific (e.g. nest age) and random effects are easily implemented with the logistic-exposure model. Application of the model to a sample of Yellow-breasted Chat (Icteria virens) nests shows that logistic-exposure estimates for individual levels of categorical explanatory variables agree closely with estimates obtained with Johnson (1979) constant-survival estimator. Use of the logistic-exposure method to model time-specific effects of nest age and date on survival of Blue-winged Teal (Anas discors) and Mallard (A. platyrhynchos) nests gives results comparable to those reported by Klett and Johnson (1982). However, the logistic-exposure approach is less subjective and much easier to implement than Klett and Johnson's method. In addition, logistic-exposure survival rate estimates are constrained to the (0,1) interval, whereas Klett and Johnson estimates are not. When applied to a sample of Mountain Plover (Charadrius montanus) nests, the logistic-exposure method gives results either identical to, or similar to, those obtained with the nest survival model in program MARK (White and Burnham 1999). I illustrate how the combination of generalized linear models and information-theoretic techniques for model selection, along with commonly available statistical software, provides ornithologists with a powerful, easily used approach to analyzing nest success.
Platyonitis oberthueri Janssens, 1942 and Epionitis tarsatus Balthasar, 1942 (Coleoptera: Scarabaeidae: Scarabaeinae: Onitini) — synonymy confirmed

The genus Epionitis Balthasar, 1942 and species Epionitis tarsatus Balthasar, 1942, were described from a single female from “Ost-Afrika, Ussambara” [= NE Tanzania] (Balthasar 1942). Earlier the same year, Janssens (1942) established the new genus Platyonitis for P. oberthueri Janssens, 1942 based on two specimens (holotype male and paratype female) from “Manica” [= Manica, Mozambique]. Krikken (1974) synonymized both these names based on study of Janssens’s types and Balthasar’s description. However, he was not able to study the holotype of E. tarsatus , so he could not fully confirm the synonymy of both type species. Krikken (1974) stated on p. 202: “Several descriptive details of E. tarsatus , based on a single female, are strongly indicative of a synonymy, but since no information on the characteristic shape of the middle femora is given by Balthasar, I prefer to postpone my final decision on the matter”. During