Miracle-dz/UniFAR-FTUs huggingface dataset:
The efficacy and safety of nemonoxacin compared with levofloxacin in the treatment of community-acquired pneumonia: a systemic review and meta-analysis of randomized controlled trials

Objectives This meta-analysis aims to assess the clinical efficacy and safety of nemonoxacin in comparison with levofloxacin in treating community-acquired pneumonia (CAP). Materials and methods The Pubmed, Embase, ClinicalTrials.gov. , and the Cochrane databases were searched up to September 2018. Only randomized controlled trials (RCTs) evaluating nemonoxacin and levofloxacin in the treatment of CAP were included. The primary outcome was the clinical cure rate, and the secondary outcomes included the microbiologic response rate and the risk of adverse events. Results Three RCTs were included. Overall, nemonoxacin and levofloxacin had similar clinical cure rates in the treatment of CAP (OR =1.05, 95% CI =0.67–1.64, I2=0%). Nemonoxacin also had a microbiologic response rate similar to levofloxacin (OR =0.89, 95% CI =0.44–1.81, I2=0%). No significant differences were found in treatment-emergent adverse events between the two drugs (OR =1.08, 95% CI =0.81–1.43, I2=0%). In subgroup analysis, the similarities in the clinical cure rate, microbiologic response rate, and risk of adverse events of these two drugs remained unchanged with the dose of nemonoxacin (500 or 750 mg) and individual pathogens. Conclusion The clinical and microbiologic efficacy of nemonoxacin is comparable to that of levofloxacin in the treatment of CAP, and this agent is as well tolerated as levofloxacin.
D-α-tocopherol polyethylene glycol 1000 succinate-modified liposomes with an siRNA corona confer enhanced cellular uptake and targeted delivery of doxorubicin via tumor priming

Background Combination therapy employing siRNAs and antitumor drugs is a promising method for the treatment of solid tumors. However, regarding combined treatments involving siRNAs and chemotherapeutic reagents, most prior research has focused on the enhanced cytotoxicity against tumor cells conferred by downregulation of the targeted protein. Purpose We developed D-α-tocopherol polyethylene glycol 1000 succinate (TPGS)-modified cationic liposomes (LPs) to simultaneously deliver doxorubicin (Dox) and the Bcl-2 siRNA (siBcl-2) for synergistic chemotherapy. The co-loading of siBcl-2 onto the Dox-loaded cationic LPs (siBcl-2/Dox-TPGS-LPs) could promote cellular uptake, cytotoxicity against 3D H22 tumor spheroids, circulation in the blood, drug accumulation at tumor sites, and synergistic chemotherapy in vivo. Methods The siBcl-2/Dox-TPGS-LPs were constructed by co-loading siBcl-2 onto the Dox-loaded TPGS-modified cationic LPs (Dox-TPGS-LPs), and Dox entrapment into the LPs was achieved using an ammonium sulfate gradient method. The antitumor effects of siBcl-2/Dox-TPGS-LPs were studied in murine hepatic carcinoma H22 cells, 3D H22 tumor spheroids, and H22 tumor-bearing mice. Results Dynamic light scattering technique and transmission electron microscopy images revealed that siBcl-2 loaded onto the Dox-TPGS-LPs formed a prominent corona at an nitrogen to phosphorus (N/P) ratio of 4:1, resulting in particle size increase from 155 to 210 nm and a weak positive zeta potential (+12.5 mV). The siBcl-2/Dox-TPGS-LPs enhanced the cellular uptake of Dox, promoted toxicity against 3D H22 tumor spheroids via tumor priming, prolonged Dox circulation in the blood, and increased accumulation of Dox at tumor sites, thereby enhancing the cytotoxicity of Dox in vitro and its chemotherapeutic efficacy in vivo. Conclusion The siBcl-2/Dox-TPGS-LPs demonstrated a strong potential for application in synergistic chemotherapy. The co-loading of siRNAs both sensitized cells toward antitumor drugs by downregulating the expression level of a specific protein and influenced the pharmacokinetic behavior of the co-delivery system in vitro and in vivo.
Research data management in practice: Results from a cross-sectional survey of health and medical researchers from an academic institution in Australia

Background: Building or acquiring research data management (RDM) capacity is a major challenge for health and medical researchers and academic institutes alike. Considering that RDM practices influence the integrity and longevity of data, targeting RDM services and support in recognition of needs is especially valuable in health and medical research. Objective: This project sought to examine the current RDM practices of health and medical researchers from an academic institution in Australia. Method: A cross-sectional survey was used to collect information from a convenience sample of 81 members of a research institute (68 academic staff and 13 postgraduate students). A survey was constructed to assess selected data management tasks associated with the earlier stages of the research data life cycle. Results: Our study indicates that RDM tasks associated with creating, processing and analysis of data vary greatly among researchers and are likely influenced by their level of research experience and RDM practices within their immediate teams. Conclusion: Evaluating the data management practices of health and medical researchers, contextualised by tasks associated with the research data life cycle, is an effective way of shaping RDM services and support in this group. Implications: This study recognises that institutional strategies targeted at tasks associated with the creation, processing and analysis of data will strengthen researcher capacity, instil good research practice and, over time, improve health informatics and research data quality.
A prospective study of the clinical outcomes and prognosis associated with comorbid COPD in the atrial fibrillation population

Background Patients with COPD are at higher risk of presenting with atrial fibrillation (AF). Information about clinical outcomes and optimal medical treatment of AF in the setting of COPD remains missing. We aimed to describe the prevalence of COPD in a sizeable cohort of real-world AF patients belonging to the same healthcare area and to examine the relationship between comorbid COPD and AF prognosis. Methods Prospective analysis performed in a specific healthcare area. Data were obtained from several sources within the “data warehouse of the Galician Healthcare Service” using multiple analytical tools. Statistical analyses were completed using SPSS 19 and STATA 14.0. Results A total of 7,990 (2.08%) patients with AF were registered throughout 2013 in our healthcare area (n=348,985). Mean age was 76.83±10.51 years and 937 (11.7%) presented with COPD. COPD patients had a higher mean CHA2DS2-VASc (4.21 vs 3.46; P=0.02) and received less beta-blocker and more digoxin therapy than those without COPD. During a mean follow-up of 707±103 days, 1,361 patients (17%) died. All-cause mortality was close to two fold higher in the COPD group (28.3% vs 15.5%; P<0.001). Independent predictive factors for all-cause mortality were age, heart failure, diabetes, previous thromboembolic event, dementia, COPD, and oral anticoagulation (OA). There were nonsignificant differences in thromboembolic events (1.7% vs 1.5%; P=0.7), but the rate of hemorrhagic events was significantly higher in the COPD group (3.3% vs 1.9%; P=0.004). Age, valvular AF, OA, and COPD were independent predictive factors for hemorrhagic events. In COPD patients, age, heart failure, vasculopathy, lack of OA, and lack of beta-blocker use were independent predictive factors for all-cause mortality. Conclusion AF patients with COPD have a higher incidence of adverse events with significantly increased rates of all-cause mortality and hemorrhagic events than AF patients without COPD. However, comorbid COPD was not associated with differences in cardiovascular death or stroke rate. OA and beta-blocker treatment presented a risk reduction in mortality while digoxin use exerted a neutral effect.
How to Prove a Secret: Zero-Knowledge Proofs on Distributed Data via Fully Linear PCPs

We introduce and study the notion of fully linear probabilistically checkable proof systems. In such a proof system, the verifier can make a small number of linear queries that apply jointly to the input and a proof vector. Our new type of proof system is motivated by applications in which the input statement is not fully available to any single verifier, but can still be efficiently accessed via linear queries. This situation arises in scenarios where the input is partitioned or secret-shared between two or more parties, or alternatively is encoded using an additively homomorphic encryption or commitment scheme. This setting appears in the context of secure messaging platforms, verifiable outsourced computation, PIR writing, private computation of aggregate statistics, and secure multiparty computation (MPC). In all these applications, there is a need for fully linear proof systems with short proofs. While several efficient constructions of fully linear proof systems are implicit in the interactive proofs literature, many questions about their complexity are open. We present several new constructions of fully linear zero-knowledge proof systems with sublinear proof size for “simple” or “structured” languages. For example, in the non-interactive setting of fully linear PCPs, we show how to prove that an input vector x ∈ F satisfies a single degree-2 equation with a proof of size O( √ n) and O( √ n) linear queries, which we show to be optimal. More generally, for languages that can be recognized by systems of constant-degree equations, we can reduce the proof size to O(log n) at the cost of O(log n) rounds of interaction. We use our new proof systems to construct new short zero-knowledge proofs on distributed and secret-shared data. These proofs can be used to improve the performance of the example systems mentioned above. Finally, we observe that zero-knowledge proofs on distributed data provide a general-purpose tool for protecting MPC protocols against malicious parties. Applying our short fully linear PCPs to “natural” MPC protocols in the honest-majority setting, we can achieve unconditional protection against malicious parties with sublinear additive communication cost. We use this to improve the communication complexity of recent honest-majority MPC protocols. For instance, using any pseudorandom generator, we obtain a 3-party protocol for Boolean circuits in which the amortized communication cost is only one bit per AND gate per party (compared to 10 bits in the best previous protocol), matching the best known protocols for semi-honest parties. ∗Stanford University. Email: dabo@cs.stanford. edu †IDC Herzliya, Israel. Email: eboyle@alum.mit. edu ‡Stanford University. Email: henrycg@cs.stanford. edu Ben-Gurion University, Israel. Email: gilboan@bgu.ac.il ¶Technion, Israel. Email: yuvali@cs.technion. ac.il
Does the “Miracle Drug” of Environmental Governance Really Improve Air Quality? Evidence from China’s System of Central Environmental Protection Inspections

Central environmental protection inspections have completed their goal of full coverage of 31 provinces in China, and more than 17,000 officials have been held accountable. The media has evaluated the effectiveness of central environmental protection inspections using the notions of “instant results” and the “miracle drug of environmental governance. ” Can this approach effectively promote local environmental governance? This paper takes the treatment effect of central environmental protection inspections on air pollution as an example. Using the method of regression discontinuity, central environmental protection inspections are found to have a positive effect on the air quality index (AQI), but this effect is only short term and unsustainable. Additionally, there are inter-provincial differences. Judging from the research results on sub-contaminants, the treatment effect of central environmental protection inspections on air pollution is mainly reflected in PM10, PM2.5 and CO. Under the current situation in which PM10 and PM2.5 are the main assessment indexes, this phenomenon indicates that due to the political achievements and promotion of local officials and for reasons of accountability, it is more effective for the central government to conduct specific environmental assessments through local governments than to conduct central environmental protection inspections.
Impact of Diabetes Mellitus and Chronic Kidney Disease on Cardiovascular Outcomes and Platelet P2Y12 Receptor Antagonist Effects in Patients With Acute Coronary Syndromes: Insights From the PLATO Trial

Background There are limited data on how the combination of diabetes mellitus (DM) and chronic kidney disease (CKD) affects cardiovascular outcomes as well as response to different P2Y12 receptor antagonists, which represented the aim of the present investigation. Methods and Results In this post hoc analysis of the PLATO (Platelet Inhibition and Patient Outcomes) trial, which randomized acute coronary syndrome patients to ticagrelor versus clopidogrel, patients (n=15 108) with available DM and CKD status were classified into 4 groups: DM+/CKD+ (n=1058), DM+/CKD− (n=2748), DM−/CKD+ (n=2160), and DM−/CKD− (n=9142). The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or stroke at 12 months. The primary safety end point was PLATO major bleeding. DM+/CKD+ patients had a higher incidence of the primary end point compared with DM−/CKD− patients (23.3% versus 7.1%; adjusted hazard ratio 2.22; 95% CI 1.88–2.63; P<0.001). Patients with DM+/CKD− and DM−/CKD+ had an intermediate risk profile. The same trend was shown for the individual components of the primary end point and for major bleeding. Compared with clopidogrel, ticagrelor reduced the incidence of the primary end point consistently across subgroups (P‐interaction=0.264), but with an increased absolute risk reduction in DM+/CKD+. The effects on major bleeding were also consistent across subgroups (P‐interaction=0.288). Conclusions In acute coronary syndrome patients, a gradient of risk was observed according to the presence or absence of DM and CKD, with patients having both risk factors at the highest risk. Although the ischemic benefit of ticagrelor over clopidogrel was consistent in all subgroups, the absolute risk reduction was greatest in patients with both DM and CKD. Clinical Trial Registration URL: http://www.clinicatrials. gov. Unique identifier: NCT00391872.
Identifying branching principles in biological networks using imaging, modeling, and machine learning

Branching in vascular networks and in overall organismic form is one of the most common and ancient features of multicellular plants, fungi and animals. These networks deliver resources and eliminate wastes from early development onward, and even play a vital role in the growth, prognosis, and treatment of tumors and stroke recovery. Because of these basic and applied reasons there is immense interest in identifying key features of vascular branching and their connection to biological function. Here we classify diverse branching networks-mouse lung, human head and torso, angiosperm plants, and gymnosperm plants-by harnessing recent advances in medical imaging, algorithms and software for extracting vascular data, theory for resource-distribution networks, and machine-learning. Specifically, we apply standard machine-learning techniques to a variety of feature spaces. Our results show that our theoretically-informed feature spaces-especially those that determine blood flow rate-combined with Kernel Density Estimation are best at distinguishing networks. Our categorization of networks enhances the mapping between biologic function-such as the dependence of metabolic rate on body mass-to vascular branching traits among organisms and organs. We accomplish this by analyzing how variation in metabolic scaling exponents-around the canonical value of 3/4-arises despite differences in vascular traits. Our results reveal how network categorization and variation in metabolic scaling are both heavily determined by scaling ratios of vessel radii-changes and asymmetries across branching generations-that strongly constrain rates of fluid flow. These linkages will improve understanding of evolutionary convergence across plants and animals while also potentially aiding prognosis and treatment of vascular pathologies and other diseased states.
Transient versus Permanent MCA Occlusion in Mice Genetically Modified to Have Good versus Poor Collaterals

Collateral-dependent blood flow is capable of significantly lessening the severity of stroke. Unfortunately, collateral flow varies widely in patients for reasons that remain unclear. Studies in mice have shown that the number and diameter of cerebral collaterals vary widely due primarily to polymorphisms in genes, e.g., Rabep2, involved in their formation during development. However, understanding how variation in collateral abundance affects stroke progression has been hampered by lack of a method to reversibly ligate the distal middle cerebral artery (MCAO) in mice. Here we present a method and examine infarct volume 24 h after transient (tMCAO, 90 min) versus permanent occlusion (pMCAO) in mice with good versus poor collaterals. Wildtype C57BL/6 mice (have abundant collaterals) sustained small infarctions following tMCAO that increased 2.1-fold after pMCAO, reflecting significant penumbra present at 90 min. Mutant C57BL/6 mice lacking Rabep2 (have reduced collaterals) sustained a 4-fold increase in infarct volume over WT following tMCAO and a smaller additional increase (0.4-fold) after pMCAO, reflecting reduced penumbra. Wildtype BALB/cBy (have a deficient Rabep2 variant and poor collaterals) had large infarctions following tMCAO that increased less (0.6-fold) than the above wildtype C57BL/6 mice following pMCAO. Mutant BALB/cBy mice (have deficient Rabep2 replaced with the C57BL/6 variant thus increased collaterals) sustained smaller infarctions after tMCAO. However, unlike C57BL/6 versus Rabep2 mice, penumbra was not increased since infarct volume increased only 0.3-fold following pMCAO. These findings present a murine model of tMCAO and demonstrate that neuroprotective mechanisms, in addition to collaterals, also vary with genetic background and affect the evolution of stroke.
Pediatric Anterior Cruciate Ligament Reruptures Are Related to Lower Functional Scores at the Time of Return to Activity: A Prospective, Midterm Follow-up Study

Background: Skeletally immature patients show a higher rate of anterior cruciate ligament (ACL) reruptures. A better understanding of the risk factors for an ACL rerupture in this population is critical. Purpose/Hypothesis: The objective of this study was to analyze preoperative, intraoperative, and postoperative characteristics of pediatric patients undergoing ACL reconstruction and determine the relationship of these factors with an ACL rerupture. It was hypothesized that patients with worse activity scores and knee function at the time of return to activity would have a higher rate of ACL reruptures at midterm follow-up. Additionally, it was hypothesized that most ACL reruptures would occur before age 20 years in the study population. Study Design: Case-control study; Level of evidence, 3. Methods: A total of 65 skeletally immature patients (age <16 years) with ACL ruptures underwent reconstruction with a quadruple hamstring tendon graft between 2002 and 2016. Of these patients, 52 were available for the study. Patient characteristics, surgical details, Tegner and Lysholm scores, and ACL reconstruction outcomes were recorded. Patients were analyzed and compared according to ACL rerupture occurrence. Results: Of the 52 patients, 18 (34.6%) experienced an ACL rerupture after reconstruction. The majority of reruptures (77.8%) occurred before age 20 years. There were 2 patients who sustained ACL reruptures during the rehabilitation period before they returned to activity. The majority of reruptures occurred after 12 months (83.2%), with 66.6% occurring after 24 months. Upon returning to activity between 6 and 9 months postoperatively, patients who ended up with intact ACL grafts reported 69% higher mean Tegner scores (P = .006) and 64% higher mean Lysholm scores than patients who sustained ACL reruptures (P < .001). Within the limits of this study, we could identify no statistical relationship between the rate of ACL reruptures and different sport types, surgical techniques, or associated injuries (P > .05). Conclusion: Skeletally immature patients who underwent ACL reconstruction and sustained ACL reruptures had lower Tegner and Lysholm scores upon returning to activity than patients without ACL reruptures. In addition, most ACL reruptures occurred in patients younger than 20 years (77.8%) and after 24 months postoperatively (66.6%).
Treatment Costs of Matrix-Associated Autologous Chondrocyte Implantation Compared With Microfracture: Results of a Matched-Pair Claims Data Analysis on the Treatment of Cartilage Knee Defects in Germany

Background: Articular cartilage damage is caused by traumatic sport accidents or age-related degeneration and might lead to osteoarthritis, which represents a socioeconomic burden to society. Cartilage damage in the knee is commonly treated surgically with microfracture (MFX) or matrix-associated autologous chondrocyte implantation (MACI). Purpose: To quantify the initial and follow-up costs associated with MFX and MACI treatments from the viewpoint of statutory health insurance in Germany. Study Design: Economic decision analysis; Level of evidence, 2. Methods: This comparative study was based on an anonymized representative claims data set of 4 million patients covered by statutory health insurance in Germany. Patients undergoing outpatient or inpatient treatment with MACI or MFX for cartilage damage in the knee between January 1, 2012, and December 31, 2013, were included and evaluated over 5 years. Groups (MACI and MFX) were adjusted via propensity score matching before initial treatment. The matched groups were compared regarding their outpatient, inpatient, pharmaceutical, and other costs during the 5-year period. Results: In total, 127 patients per group were analyzed (59.1% male, 40.9% female; mean age, 37 years). In the year of the initial surgical procedure, costs were €14,804.13 in the MACI group and €5458.59 in the MFX group. In years 2 and 3 after initial surgery, treatment costs were comparable between patients treated with MACI (€2897.97 and €2114.87, respectively) and MFX (€2842.66 and €1967.42, respectively), with slightly higher treatment costs for those treated with MACI. In years 4 and 5 after surgery, costs were less in patients treated with MACI (€2154.79 and €1478.08, respectively) than in those treated with MFX (€2232.57 and €2061.63, respectively). Costs related to revision surgery were, on average, €3732 for MACI and €3765 for MFX. Thus, additional costs in years with revision surgery were €1672 for MACI and €1915 for MFX. Conclusion: This was the first study to analyze a large representative population claims database with propensity score matching, and results indicated that follow-up costs of patients treated with MACI and MFX began to converge over time. We found that total costs for MACI were higher than for MFX but that additional costs for MACI were lower than previously reported. Perceived morbidity may have little to do with cost.