Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical Course of Acute Ischemic Stroke Due to Medium Vessel Occlusion With and Without Intravenous Alteplase Treatment

Supplemental Digital Content is available in the text. Background and Purpose: Available data on the clinical course of patients with acute ischemic stroke due to medium vessel occlusion (MeVO) are mostly limited to those with M2 segment occlusions. Outcomes are generally better compared with more proximal occlusions, but many patients will still suffer from severe morbidity. We aimed to determine the clinical course of acute ischemic stroke due to MeVO with and without intravenous alteplase treatment. Methods: Patients with MeVO (M2/M3/A2/A3/P2/P3 occlusion) from the INTERRSeCT (The Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography) and PRoveIT (Precise and Rapid Assessment of Collaterals Using Multi-Phase CTA in the Triage of Patients With Acute Ischemic Stroke for IA Therapy) studies were included. Baseline characteristics and clinical outcomes were summarized using descriptive statistics. The primary outcome was a modified Rankin Scale score of 0 to 1 at 90 days, describing excellent functional outcome. Secondary outcomes were the common odds ratio for a 1-point shift across the modified Rankin Scale and functional independence, defined as modified Rankin Scale score of 0 to 2. We compared outcomes between patients with versus without intravenous alteplase treatment and between patients who did and did not show recanalization on follow-up computed tomography angiography. Logistic regression was used to provide adjusted effect-size estimates. Results: Among 258 patients with MeVO, the median baseline National Institutes of Health Stroke Scale score was 7 (interquartile range: 5–12). A total of 72.1% (186/258) patients were treated with intravenous alteplase and in 41.8% (84/201), recanalization of the occlusion (revised arterial occlusive lesion score 2b/3) was seen on follow-up computed tomography angiography. Excellent functional outcome was achieved by 50.0% (129/258), and 67.4% (174/258) patients gained functional independence, while 8.9% (23/258) patients died within 90 days. Recanalization was observed in 21.4% (9/42) patients who were not treated with alteplase and 47.2% (75/159) patients treated with alteplase (P=0.003). Early recanalization (adjusted odds ratio, 2.29 [95% CI, 1.23–4.28]) was significantly associated with excellent functional outcome, while intravenous alteplase was not (adjusted odds ratio, 1.70 [95% CI, 0.88–3.25]). Conclusions: One of every 2 patients with MeVO did not achieve excellent clinical outcome at 90 days with best medical management. Early recanalization was strongly associated with excellent outcome but occurred in <50% of patients despite intravenous alteplase treatment.
Determining if Telehealth Can Reduce Health System Costs: Scoping Review

Background Telehealth represents an opportunity for Australia to harness the power of technology to redesign the way health care is delivered. The potential benefits of telehealth include increased accessibility to care, productivity gains for health providers and patients through reduced travel, potential for cost savings, and an opportunity to develop culturally appropriate services that are more sensitive to the needs of special populations. The uptake of telehealth has been hindered at times by clinician reluctance and policies that preclude metropolitan populations from accessing telehealth services. Objective This study aims to investigate if telehealth reduces health system costs compared with traditional service models and to identify the scenarios in which cost savings can be realized. Methods A scoping review was undertaken to meet the study aims. Initially, literature searches were conducted using broad terms for telehealth and economics to identify economic evaluation literature in telehealth. The investigators then conducted an expert focus group to identify domains where telehealth could reduce health system costs, followed by targeted literature searches for corresponding evidence. Results The cost analyses reviewed provided evidence that telehealth reduced costs when health system–funded travel was prevented and when telehealth mitigated the need for expensive procedural or specialist follow-up by providing competent care in a more efficient way. The expert focus group identified 4 areas of potential savings from telehealth: productivity gains, reductions in secondary care, alternate funding models, and telementoring. Telehealth demonstrated great potential for productivity gains arising from health system redesign; however, under the Australian activity-based funding, it is unlikely that these gains will result in cost savings. Secondary care use mitigation is an area of promise for telehealth; however, many studies have not demonstrated overall cost savings due to the cost of administering and monitoring telehealth systems. Alternate funding models from telehealth systems have the potential to save the health system money in situations where the consumers pay out of pocket to receive services. Telementoring has had minimal economic evaluation; however, in the long term it is likely to result in inadvertent cost savings through the upskilling of generalist and allied health clinicians. Conclusions Health services considering implementing telehealth should be motivated by benefits other than cost reduction. The available evidence has indicated that although telehealth provides overwhelmingly positive patient benefits and increases productivity for many services, current evidence suggests that it does not routinely reduce the cost of care delivery for the health system.
Azithromycin resistance mutations in Streptococcus pneumoniae as revealed by a chemogenomic screen

We report on the combination of chemical mutagenesis, azithromycin selection and next-generation sequencing (Mut-Seq) for the identification of small nucleotide variants that decrease the susceptibility of Streptococcus pneumoniae to the macrolide antibiotic azithromycin. Mutations in the 23S ribosomal RNA or in ribosomal proteins can confer resistance to macrolides and these were detected by Mut-Seq. By concentrating on recurrent variants, we could associate mutations in genes implicated in the metabolism of glutamine with decreased azithromycin susceptibility among S. pneumoniae mutants. Glutamine synthetase catalyses the transformation of glutamate and ammonium into glutamine and its chemical inhibition is shown to sensitize S. pneumoniae to antibiotics. A mutation affecting the ribosomal-binding site of a putative ribonuclease J2 is also shown to confer low-level resistance. Mut-Seq has the potential to reveal chromosomal changes enabling high resistance as well as novel events conferring more subtle phenotypes.
Phase II trial of individualized/dynamic cisplatin regimens for definitive concurrent chemoradiation therapy in patients with head and neck squamous cell carcinoma

The current standard cisplatin regimen for concurrent chemoradiation therapy (CCRT) involves generalized static administration of cisplatin without considering patient characteristics and patient/tumor responses during treatment. We aimed to evaluate the oncological feasibility of individualized/dynamic cisplatin regimens for definitive CCRT in patients with head and neck squamous cell carcinoma (HNSCC). This prospective, single‐center study enrolled patients with biopsy‐confirmed HNSCC for whom CCRT was indicated as the primary treatment. Concurrent with radiation therapy (RT), patients received individualized and dynamically modified cisplatin chemotherapy based on patient characteristics, such as age and Eastern Cooperative Oncology Group performance status (PS), and patient/tumor treatment responses. The primary endpoints of the study were grade ≥3 toxicity and progression‐free survival (PFS). The study enrolled 150 patients; 146 (97.3%) received ≥2 cycles of cisplatin in addition to scheduled RT. Incidence of any grade 3‐4 toxicities was 40.7% (61/150). During the 40.1 ± 25.1‐month follow‐up period, the 2‐year locoregional control, distant control, PFS, disease‐specific survival, and overall survival were 81.7%, 89.2%, 73.0%, 89.2%, and 86.1%, respectively. The treatment compliance and grade ≥3 toxicities did not differ between patients aged <70 years and ≥70 years, or those with PS 0 and PS 1‐2, respectively. CCRT using individualized, dynamic cisplatin regimens based on patient age, PS, and patient/tumor responses during treatment was oncologically safe and effective for treating patients with HNSCC, including those aged ≥70 years and with PS 1‐2.
The circadian gene Cryptochrome 2 influences stress‐induced brain activity and depressive‐like behavior in mice

Cryptochrome 2 (Cry2) is a core clock gene important for circadian regulation. It has also been associated with anxiety and depressive‐like behaviors in mice, but the previous findings have been conflicting in terms of the direction of the effect. To begin to elucidate the molecular mechanisms of this association, we carried out behavioral testing, PET imaging, and gene expression analysis of Cry2−/− and Cry2+/+ mice. Compared to Cry2+/+ mice, we found that Cry2−/− mice spent less time immobile in the forced swim test, suggesting reduced despair‐like behavior. Moreover, Cry2−/− mice had lower saccharin preference, indicative of increased anhedonia. In contrast, we observed no group differences in anxiety‐like behavior. The behavioral changes were accompanied by lower metabolic activity of the ventro‐medial hypothalamus, suprachiasmatic nuclei, ventral tegmental area, anterior and medial striatum, substantia nigra, and habenula after cold stress as measured by PET imaging with a glucose analog. Although the expression of many depression‐associated and metabolic genes was upregulated or downregulated by cold stress, we observed no differences between Cry2−/− and Cry2+/+ mice. These findings are consistent with other studies showing that Cry2 is required for normal emotional behavior. Our findings confirm previous roles of Cry2 in behavior and extend them by showing that the effects on behavior may be mediated by changes in brain metabolism.
Quantitative Benefit–Risk Assessment of P‐gp–Mediated Drug–Drug Interactions of Dabigatran Coadministered With Pharmacokinetic Enhancers in Patients With Renal Impairment

Drug–drug interactions (DDIs) between dabigatran and ritonavir/cobicistat are of major concern in people living with HIV, particularly in those with impaired renal function, because they can result in increased dabigatran exposure and thus an increased risk of major bleeding events. However, the extent of this interaction and subsequent need for dose adjustment in subjects with varying degrees of renal function is currently not yet fully understood. To close this knowledge gap, we conducted an integrated population physiologically‐based pharmacokinetic/pharmacodynamic analysis linking changes in dabigatran exposure due to DDIs and varying degrees of renal function to the probability of experiencing an ischemic stroke or major bleeding event within 1 year. The results of our analysis suggest that coadministration of dabigatran etexilate (dabigatran prodrug) and ritonavir/cobicistat should be avoided in subjects with severe renal impairment. A 2‐hour dose separation or dabigatran etexilate dose reduction to 110 mg b.i. d. (twice daily) should be considered in subjects with moderate renal impairment when coadministered with ritonavir, while the dabigatran etexilate dose should be further reduced to 75 mg b.i. d. when coadministered with cobicistat. No dabigatran etexilate dose adjustment is needed in subjects with normal renal function receiving ritonavir, but dabigatran etexilate dose reduction to 110 mg b.i. d. should be considered when coadministered with cobicistat.
Mas Receptor Activation Contributes to the Improvement of Nitric Oxide Bioavailability and Vascular Remodeling During Chronic AT1R (Angiotensin Type-1 Receptor) Blockade in Experimental Hypertension

Supplemental Digital Content is available in the text. Angiotensin (1–7) production increases during AT1R (angiotensin type-1 receptor) blockade. The contribution of Ang (1–7) (angiotensin [1–7]) and its receptor (MasR) to the favorable effect of angiotensin receptor blockers on remodeling and function of resistance arteries remains unclear. We sought to determine whether MasR contributes to the improvement of vascular structure and function during chronic AT1R blockade. Spontaneously hypertensive rats were treated with Ang (1–7) or olmesartan ± MasR antagonist A-779, or vehicle, for 14 days. Blood pressure was measured by tail cuff methodology. Mesenteric arteries were dissected and mounted on a pressurized micromyograph to evaluate media-to-lumen ratio (M/L) and endothelial function. Expression of MasR and eNOS (endothelial nitric oxide synthase) was evaluated by immunoblotting, plasma nitrate by colorimetric assay, and reactive oxygen species production by dihydroethidium staining. Independently of blood pressure, olmesartan significantly reduced M/L and improved NO bioavailability, A-779 prevented these effects. Likewise, Ang (1–7) significantly reduced M/L and NO bioavailability. MasR expression was significantly increased by Ang (1–7) as well as by olmesartan, and it was blunted in the presence of A-779. Both Ang (1–7) and olmesartan increased eNOS expression and plasma nitrite which were reduced by A-779. Superoxide generation was attenuated by olmesartan and Ang (1–7) and was blunted in the presence of A-779. These MasR-mediated actions were independent of AT2R activation since olmesartan and Ang (1–7) increased MasR expression and reduced M/L in Ang II (angiotensin II)–infused AT2R knockout mice, independently of blood pressure control. A-779 prevented these effects. Hence, MasR activation may contribute to the favorable effects of AT1R antagonism on NO bioavailability and microvascular remodeling, independently of AT2R activation and blood pressure control.
Accelerometry predicts muscle ultrastructure and flight capabilities in a wild bird

ABSTRACT Muscle ultrastructure is closely linked with athletic performance in humans and lab animals, and presumably plays an important role in the movement ecology of wild animals. Movement is critical for wild animals to forage, escape predators and reproduce. However, little evidence directly links muscle condition to locomotion in the wild. We used GPS-accelerometers to examine flight behaviour and muscle biopsies to assess muscle ultrastructure in breeding black-legged kittiwakes (Rissa tridactyla). Biopsied kittiwakes showed similar reproductive success and subsequent over-winter survival to non-biopsied kittiwakes, suggesting that our study method did not greatly impact foraging ability. Muscle fibre diameter was negatively associated with wing beat frequency, likely because larger muscle fibres facilitate powered flight. The number of nuclei per fibre was positively associated with average air speed, likely because higher power output needed by faster-flying birds required plasticity for muscle fibre recruitment. These results suggest the potential for flight behaviour to predict muscle ultrastructure. Highlighted Article: Comparison of flight characteristics with flight muscle ultrastructure in a seabird reveals that wing beat frequency is negatively correlated with fibre diameter and average air speed is positively correlated with the number of nuclei per fibre.
Pyrosequencing study of caecal bacterial community of rabbit does and kits from a farm affected by epizootic rabbit enteropathy

Epizootic Rabbit Enteropathy (ERE) is a disease of unknown aetiology that mainly affects post-weaning animals. Caecotrophs from animals in a farm affected by ERE were analysed to identify changes in the microbiological profile of growing rabbits. Does and kits at weaning (28 d) and the same rabbits ten days later (38 d) were used for a comparison using Roche 454 pyrosequencing of hypervariable V3-V5 regions of the 16S rRNA genes. The caecal bacterial community was dominated by the Firmicutes phylum (about 80%), followed by Bacteroidetes (15%), although relative abundances changed according to animal age (among does and kits at 28 and 38 d) and health status (affected or not by ERE). Two dominant families were classified within the Firmicutes phylum: Ruminococcaceae and Lachnospiraceae (50 and 20% of the sequences, respectively). In kits affected by ERE, relative abundance of Ruminococcus and Bacteroides genera decreased and increased, respectively, compared to healthy kits at the same age (28 and 38 d). The principal coordinate analysis plot revealed that kits at 28 d of age cluster together and apart from the does and the healthy 38-d rabbit groups. When only growing rabbits are considered, kits that showed symptoms of ERE clustered separately. Results suggest a different caecal bacterial community of rabbits affected by ERE. These findings highlight the need to identify different stages of the disease.
Association of Bevacizumab Plus Oxaliplatin-Based Chemotherapy With Disease-Free Survival and Overall Survival in Patients With Stage II Colon Cancer

Key Points Question What was the efficacy of adjuvant bevacizumab on disease-free and overall survival among patients with curatively resected high-risk stage II colon cancer? Findings In this secondary analysis of 573 patients with high-risk stage II colon cancer enrolled in the AVANT trial, the addition of bevacizumab to oxaliplatin-based chemotherapy did not prolong disease-free survival or overall survival. The 5-year survival rates in patients with high-risk stage II colon cancer in this study were 89.7% in the FOLFOX4 control group and in the FOLFOX4 with bevacizumab group and 93.2% in the XELOX with bevacizumab group. Meaning The findings of this study suggest that adding bevacizumab to oxaliplatin-based chemotherapy was not associated with longer DFS or OS in patients with high-risk stage II colon cancer and that the definition of high-risk stage II colon cancer needs to be revisited.
Patient‐specific quality assurance using machine log files analysis for stereotactic body radiation therapy (SBRT)

Abstract An in‐house trajectory log analysis program (LOGQA) was developed to evaluate the delivery accuracy of volumetric‐modulated arc therapy (VMAT) for stereotactic body radiation therapy (SBRT). Methods have been established in LOGQA to provide analysis on dose indices, gantry angles, and multi‐leaf collimator (MLC) positions. Between March 2019 and May 2020, 120 VMAT SBRT plans of various treatment sites using flattening filter‐free (FFF) mode were evaluated using both LOGQA and phantom measurements. Gantry angles, dose indices, and MLC positions were extracted from log and compared with each plan. Integrated transient fluence map (ITFM) was reconstructed from log to examine the deviation of delivered fluence against the planned one. Average correlation coefficient of dose index versus gantry angle and ITFM for all patients were 1.0000, indicating that the delivered beam parameters were in good agreement with planned values. Maximum deviation of gantry angles and monitor units (MU) of all patients were less than 0.2 degree and 0.03 % respectively. Regarding MLC positions, maximum and root‐mean‐square (RMS) deviations from planned values were less than 0.6 mm and 0.3 mm respectively, indicating that MLC positions during delivery followed planned values in precise manner. Results of LOGQA were consistent with measurement, where all gamma‐index passing rates were larger than 95 %, with 2 %/2 mm criteria. Three types of intentional errors were introduced to patient plan for software validation. LOGQA was found to recognize the introduced errors of MLC positions, gantry angles, and dose indices with magnitudes of 1 mm, 1 degree, and 5 %, respectively, which were masked in phantom measurement. LOGQA was demonstrated to have the potential to reduce or even replace patient‐specific QA measurements for SBRT plan delivery provided that the frequency and amount of measurement‐based machine‐specific QA can be increased to ensure the log files record real values of machine parameters.
The effect of aqueous leaf extract of fluted pumpkin on some hematological parameters and liver enzymes in 2,4-dinitrophenylhydrazine- induced anemic rats

Anemia constitutes a serious health problem in many tropical countries including Nigeria because of the prevalence of malaria and other parasitic infections which possibly leads to decrease of hemoglobin. Fluted pumpkin has been reported to be very good in building the constituents of the blood and also replacing them. This study was designed to investigate the effects of the aqueous leaf extract of fluted pumpkin on some hematological parameters and liver enzymes; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in 2, 4-dinitrophenylhydrazine-induced anemia in experimental rat. Twelve Wister albino male rats were obtained from a nearby farm and separated into four groups of three rats each for the study. Rats in Groups 1 and 2 were injected 40 mg/kg 2, 4-dinitrophenylhydrazine for eight days to induce anemia, while rats in Groups 3 and 4 were fed with grower’s mash and water ad libitum. All analysis was done using the standard methods. The result of this study shows that, oral administration of 50 mg/kg of aqueous leaf extract of fluted pumpkin to the rats in induced treated and normal treated groups (Groups 1 and 3), increased the hematological parameters under investigation while the rest remained significantly unchanged. Low level of ALT and AST was observed in rats in group 1 (induced treated group) suggesting a hepatoprotective property of the leaf extract which also indicate that the extract had no effect on the liver of the rats at the concentration used. The result of this research indicate that 50 mg/kg aqueous leaf extract of fluted pumpkin could elevate the packed cell volume, red blood cells and hemoglobin concentration in the rats induced with 2, 4-dinitrophenylhydrazine. Hence, oral administration of the extract could cure hemolytic anemia. The leaf extract also regulated the liver enzymes (ALT and AST) of the rats induced with 2, 4-dinitrophenylhydrazine. It can be concluded that aqueous leaf extract of fluted pumpkin is a potential blood booster and has hepatoprotective property. Key words: Fluted pumpkin, hematological parameters, liver enzymes, 2, dinitrophenylhydrazine, anemia.
Towards culturing the microbe of your choice.

Principal challenges in environmental microbiology include determining the functions of specific microorganisms, when and where those functions change, and why. Unveiling this information for creatures on the micron scale is exquisitely difficult, but culturing microorganisms offers a sturdy experimental foundation for such queries. Unfortunately, bringing microbes into culture presents its own set of challenges, which, combined with their vast diversity, means most microorganisms remain uncultivated (Schloss et al., 2016; Lloyd et al., 2018; Steen et al., 2019). Microbiologists may know a microbe's exact size, location, abundance, and the fine details of its genome, but still struggle to bring it into culture. But what if we could culture any microorganism we wanted at will? In fact, researchers have already taken the first steps towards this future, and additional emerging technologies will help make culturing the microbe of your choice a reality. This article is protected by copyright. All rights reserved.