Miracle-dz/UniFAR-FTUs huggingface dataset:
A Retrospective Cohort Study of the 2018 Angiotensin Receptor Blocker (ARB) Recalls and Subsequent Drug Shortages on Patients with Hypertension

Purpose: In July 2018, the Food and Drug Administration recalled valsartan due to carcinogenic impurities, leading to an unprecedented drug shortage leading to management challenges impacting a large population of valsartan users. However, the extent to which the valsartan recall impacted clinical outcomes is unknown. Our objective was to compare the risk of adverse events between patients with hypertension using valsartan and a propensity-score-matched group of patients using non-recalled angiotensin receptor blockers (ARBs) and angiotensin converting enzyme-inhibitors (ACE-Is). Methods: We conducted a retrospective cohort analysis of Optum's de-identified Clinformatics(R) Datamart (July 2017-January 2019). Adults with hypertension who received valsartan were compared to persons who received non-recalled ARBs and ACE-Is for 1 year prior to and on the recall date. The primary outcomes were measured in the 6 months following the recall date included: 1) a composite measure of all-cause hospitalization, all-cause emergency department (ED) and all-cause urgent care (UC) visit, 2) a composite cardiac event measure of hospitalizations for acute myocardial infarction and hospitalizations/ED/UC visits for stroke/transient ischemic attack, heart failure or hypertension. Cox proportional hazard models compared the risk of outcomes between propensity-score-matched treatment groups. Results: Of adults with hypertension, 76,934 received valsartan at the time of the recall and 509,742 received a non-recalled ARB/ACE-I. Valsartan use at the time of the recall was associated with a combined increased risk of all-cause hospitalization, ED or UC use (HR 1.02; 95% CI: 1.00-1.04) and of the composite of cardiac events (HR 1.22; 95% CI: 1.15-1.29) within six-months after the recall. Conclusions: The national valsartan recall and subsequent shortage had negative consequences for patients with hypertension. As the threat of shortages increases for drugs that treat common outpatient conditions, systems at the local- and national-levels need to be strengthened to protect patients from drug shortages by providing them with safe and reliable alternatives.
Coupled Environmental Processes and Long-term Performance of Landfill Covers in the northern Mojave Desert

Evapotransiration (ET) covers have gained widespread acceptance as a closure feature for waste disposal sites, particularly in the arid and semi-arid regions of the southwestern U.S. But as landforms, ET covers are subject to change over time because of processes such as pedogenesis, hydrologic processes, vegetation establishment and change, and biological processes. To better understand the effects of coupled process changes to ET covers, a series of four primary analog sites in Yucca Flat on the Nevada Test Site, along with measurements and observations from other locations in the Mojave Desert, were selected to evaluate changes in ET covers over time. The analog sites, of varying ages, were selected to address changes in the early post-institutional control period, the 1,000-year compliance period for disposal of low-level and mixed low-level waste, and the 10,000-year compliance period for transuranic waste sites.
Species distribution and antifungal susceptibility profile of Candida spp isolated from urine of hospitalized patients in Dschang District Hospital, Cameroon

Candiduria refers to the presence of Candida species in urine, It is a common nosocomial infection afflicting the urinary tract. The aim of our study was to determine the prevalence of candiduria in hospitalized patients in Dschang District Hospital, and to evaluate the susceptibility patterns of Candida spp isolated from some commonly used antifungal drugs. Midstream urine samples were collected from 122 hospitalized patients at the Dschang District Hospital, then speciation of Candida was done based on colony colour on CHROMagar Candida medium. Antifungal susceptibility testing of the isolates was performed by the Broth dilution method. A total of 51 isolates of Candida species were recovered from 122 urine samples. Candida albicans was the most prevalent species 41.2% (21 isolates), followed by C. parapsilosis (27.5%), C. glabrata (17.6%), C. krusei (7.8%) and C. tropicalis (5.9%). Antifungal susceptibility test indicated that 100% and 96.1% of the Candida isolates were resistant to Amphotericin B and Nystatin respectively. Resistance varied depending on the species and the respective antifungal agents. We can conclude that candiduria is relatively common in hospitalized patients. The isolates were very resistant to polyenes (amphotericin B and nystatin) and most isolates were sensitive to azoles. Therefore, the species identification of Candida isolates along with their antifungal susceptibility pattern can help the clinicians in adequate treatment of the patients with candiduria. Keywords : Candiduria, Candida spp, Hospitalized patients, Antifungal susceptibility.
Hybrid Parameter Search and Dynamic Model Selection for Mixed-Variable Bayesian Optimization

This paper presents a new type of hybrid model for Bayesian optimization (BO) adept at managing mixed variables, encompassing both quantitative (continuous and integer) and qualitative (categorical) types. Our proposed new hybrid models (named hybridM) merge the Monte Carlo Tree Search structure (MCTS) for categorical variables with Gaussian Processes (GP) for continuous ones. hybridM leverages the upper confidence bound tree search (UCTS) for MCTS strategy, showcasing the tree architecture's integration into Bayesian optimization. Our innovations, including dynamic online kernel selection in the surrogate modeling phase and a unique UCTS search strategy, position our hybrid models as an advancement in mixed-variable surrogate models. Numerical experiments underscore the superiority of hybrid models, highlighting their potential in Bayesian optimization.
Long-term outcomes of therapeutic corneal transplants performed in a tertiary eye care hospital in South India

Purpose: This study aimed to review the demographics, clinical characteristics, and long-term outcomes of therapeutic penetrating keratoplasty (TPK) performed in a tertiary eye care hospital. Methods: Case records of 149 therapeutic transplants (135 patients) that were performed during the calendar year 2016 were retrospectively analyzed, and outcomes were measured until 3 years of follow-up. Information on demographics, presentation characteristics, keratoplasty indications, offending microbe, and secondary surgical interventions was studied. The final outcome was classified in terms of therapeutic, anatomical, and functional outcomes. Results: The median age of the recipients was 55 years with 61% men. The most common indications for TPK were perforated infectious ulcer (45.9%), nonhealing ulcers (29.9%), and graft infections (17.4%). Fungal etiology was noted in 61.2% and bacterial etiology in 17.4% of the eyes. Therapeutic success was achieved in 130 eyes (89%) at the end of 1 month. Anatomical success was achieved in 130 (98.5%) and 88 patients (86.3%) at the end of 1 and 6 months, respectively. At the 6-month time point, 78 patients (76.5%) attained functional success with vision better than light perception. Three-year follow-up data were available for 23.7% of recipients, of which only 12 patients (37.5%) retained a clear graft either after a primary therapeutic or secondary optical keratoplasty. Conclusion: Therapeutic keratoplasty is highly effective in eradicating infection and providing anatomical integrity. However, timely intervention can aid in achieving the best functional outcome.
The context of REDD+ in Mozambique: drivers, agents and institutions.

This publication offers an overview of REDD+ strategy in Mozambique through a synthesis of the current knowledge about the causes of forest carbon changes, a review of the legal and institutional context, and a description of the current political process of REDD+. The objective of the study is to collate data and relevant information, and to offer a preliminary analysis of the fundamental aspects that can help promote efficiency, efficacy, and equity in REDD+ policy. Specifically, this study concludes that some of the major problems for REDD+ in Mozambique are the lack of data about deforestation and forest degradation, institutional weakness (regarding monitoring and propriety rights), and gaps in human and technical capacity to fulfil demands associated with REDD+. Therefore, efficient results will depend on the degree to which REDD+ policies are oriented toward real mitigation of the sources of forest carbon changes. In Mozambique, REDD+ policy tends to originate outside the timber sector. The cost-effectiveness of the results will depend on identifying and addressing the fundamental causes of forest carbon changes through more viable REDD+ policy options; government capacity to respond to REDD+ demands, especially at the sub-national level; the capacity of civil society and other institutions; and the strength of the institutional framework. The degree of success of equitable outcomes and the generation of co-benefits will depend on the inclusion and appropriateness of the processes at the national level; if those who support REDD+ costs are also being compensated; and on the general definition of carbon rights and environmental services.
Bacterial Lipopolysaccharides Exacerbate Neurogenic Heterotopic Ossification Development

Neurogenic heterotopic ossifications (NHO) are heterotopic bones that develop in periarticular muscles after severe central nervous system (CNS) injuries. Several retrospective studies have shown that NHO prevalence is higher in patients who suffer concomitant infections. However, it is unclear whether these infections directly contribute to NHO development or reflect the immunodepression observed in patients with CNS injury. Using our mouse model of NHO induced by spinal cord injury (SCI) between vertebrae T11 to T13, we demonstrate that lipopolysaccharides (LPS) from gram‐negative bacteria exacerbate NHO development in a toll‐like receptor‐4 (TLR4)‐dependent manner, signaling through the TIR‐domain‐containing adapter‐inducing interferon‐β (TRIF/TICAM1) adaptor rather than the myeloid differentiation primary response‐88 (MYD88) adaptor. We find that T11 to T13 SCI did not significantly alter intestinal integrity nor cause intestinal bacteria translocation or endotoxemia, suggesting that NHO development is not driven by endotoxins from the gut in this model of SCI‐induced NHO. Relevant to the human pathology, LPS increased expression of osteoblast markers in cultures of human fibro‐adipogenic progenitors isolated from muscles surrounding NHO biopsies. In a case–control retrospective study in patients with traumatic brain injuries, infections with gram‐negative Pseudomonas species were significantly associated with NHO development. Together these data suggest a functional association between gram‐negative bacterial infections and NHO development and highlights infection management as a key consideration to avoid NHO development in patients. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
A Reassessment of the Relationship Between Inequality and Growth

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CAN DIODE LASER SUPPORT REMINERALIZATION POTENTIAL OF CPP-ACPF ON DEMINERALIZED ENAMEL?.

Recent studies recognized that incorporation of fluoride into the Casein Phospho-Peptide - Amorphous Calcium Phosphate (CPP-ACP) structure forming (CPP-ACPF): (GC MI paste Plus), produced greater remineralization than the CPP-ACP alone. The aim of the present study was to assess the efficacy of diode laser irradiation on remineralization potential of CPP-ACPF cream on induced human surface enamel demineralization, using Scanning Electron Microscope-Energy Dispersive X- ray analysis SEM-EDAX analyser. Materials & Methods: forty intact premolars were collected and thirty of them were immersed in a demineralizing solution for 10 weeks to induce caries like lesions and then were divided into four groups, each consist of 10 teeth. In C-ve group the specimens were immersed in normal saline only C+ve group specimens were subjected only to demineralizing solution. In Group (CPP-ACPF Diode laser irradiation on remineralization potential of CPP-ACPF cream on human surface enamel induced caries like lesions, using Scanning Electron Microscope- Energy Dispersive X- ray analysis SEM-EDAX.
Comparison of intraocular lens power prediction accuracy of formulas in American Society of Cataract and Refractive Surgery post-refractive surgery calculator in eyes with prior radial keratotomy

Purpose: To evaluate the accuracy of intraocular lens (IOL) power prediction of the formulas available on the American Society of Cataract and Refractive Surgery (ASCRS) post-refractive calculator in eyes with prior radial keratotomy (RK) for myopia. Methods: This retrospective study included 25 eyes of 18 patients whose status was post-RK for treatment of myopia, which had undergone cataract extraction with IOL implantation. Prediction error was calculated as the difference between implanted IOL power and predicted power by various formulae available on ASCRS post-refractive calculator. The formulas compared were Humphrey Atlas method, IOLMaster/Lenstar method, Barrett True-K no-history formula, ASCRS Average power, and ASCRS Maximum power on ASCRS post-refractive calculator. Results: Median absolute errors were the least for Barrett True-K and ASCRS Maximum power, that is, 0.56 (0.25, 1.04) and 0.56 (0.25, 1.06) D, respectively, and that of Atlas method was 1.60 (0.85, 2.28) D. Median arithmetic errors were positive for Atlas, Barrett True-K, ASCRS Average (0.86 [−0.17, 1.61], 0.14 [−0.22 to 0.54], and 0.23 [−0.054, 0.76] D, respectively) and negative for IOLMaster/Lenstar method and ASCRS Maximum power (−0.02 [−0.46 to 0.38] and − 0.48 [−1.06 to − 0.22] D, respectively). Multiple comparison analysis of Friedman's test revealed that Atlas formula was significantly different from IOLMaster/Lenstar, Barrett True-K, and ASCRS Maximum power; ASCRS Maximum power was significantly different from all others (P < 0.00001). Conclusion: In post-RK eyes, Barrett True-K no-history formula and ASCRS Maximum power given by the ASCRS calculator were more accurate than other available formulas, with ASCRS Maximum leading to more myopic outcomes when compared to others.
The Hyper-log-chromaticity space for illuminant invariance

Variation in illumination conditions through a scene is a common issue for classification, segmentation and recognition applications. Traffic monitoring and driver assistance systems have difficulty with the changing illumination conditions at night, throughout the day, with multiple sources (especially at night) and in the presence of shadows. The majority of existing algorithms for color constancy or shadow detection rely on multiple frames for comparison or to build a background model. The proposed approach uses a novel color space inspired by the Log-Chromaticity space and modifies the bilateral filter to equalize illumination across objects using a single frame. Neighboring pixels of the same color, but of different brightness, are assumed to be of the same object/material. The utility of the algorithm is studied over day and night simulated scenes of varying complexity. The objective is not to provide a product for visual inspection but rather an alternate image with fewer illumination related issues for other algorithms to process. The usefulness of the filter is demonstrated by applying two simple classifiers and comparing the class statistics. The hyper-log-chromaticity image and the filtered image both improve the quality of the classification relative to the un-processed image.
Outcomes and prognostic factors of patients with Extranodal NK T cell lymphoma (ENKTL)

Abstract The staging, prognostication, and treatment of ENKTL has evolved over the years with better understanding of the disease biology. There is significant heterogeneity in the treatment followed across the world. Literature from India have been few with small number of patients. We studied the outcomes and prognostic factors of patients with ENKTL treated between May 2010 and December 2021 at our center. A total of 78 patients diagnosed with ENKTL were treated at our center. L-asparaginase based chemotherapy was administered in 84% of the patients. Close to 2/3rd patients received SMILE chemotherapy. After a median follow-up of 30 months (18.5–41.4 months), the median relapse free survival and overall survival for the overall population was 45 months (12–118 months) and 45 months (14–118 months) respectively. By multivariate analysis, PINK score of 2–4, non-receipt of RT and non-achievement of CR were associated with poor survival.
Antibiotic prophylaxis for cataract surgery - Practice patterns amongst Indian Ophthalmologists

Purpose: To assess the current trends in use of perioperative antibiotic prophylaxis, especially intracameral antibiotics (ICAB), for cataract surgery in India. Methods: This was an E-survey using a previously validated questionnaire carried out by the All India Ophthalmological Society (AIOS) in August 2022. An E-mail invitation to complete an online 40-point survey was sent to all members of the AIOS using a digital E-mail service (Survey Monkey) and social media platforms. Results: Out of 1804 total respondents, 58% (n = 1022) reported using routine ICAB prophylaxis. Of those using ICAB, 89% (n = 909) reported using it for all cases, whereas the rest used it for specific indications such as post-PC rent (n = 43), one eyed patient (n = 19), and high-risk cases (n = 50). Commercially available moxifloxacin was by far the commonest agent used for ICAB (n = 686, 67%). Eighty respondents (8%) reported noticing occasional toxic reactions and nontoxic corneal edema (n = 64, 6%) with ICAB. Surgeons with >10 years' experience especially practicing in medical colleges used fewer ICAB (OR = 0.52, 95%CI = 0.38 – 0.72, P < 0,001) compared to younger surgeons (<5-year experience) in solo clinics. The commonest reason for nonadoption of IC antibiotics was “unconvinced of the need to use it in my setting” (n = 296, 52% of those who answered this question). Conclusion: IC antibiotic prophylaxis for cataract surgery has significantly increased in India from 40% in 2017 to 58% in 2022. Commercially available moxifloxacin was preferred by the majority users. Intraocular inflammation may occur occasionally and needs safer formulations to avoid this.
Urinary congophilia in pregnancy: a marker of kidney injury rather than preeclampsia

Background: The differentiation between preeclampsia and similarly presenting kidney disease in pregnancy is a diagnostic challenge. Although some laboratory tests have been utilized, globally validated tools are yet needed, particularly in resource-limited settings. Congophilic proteins are abundantly detected in the urine of pregnant women who develop preeclampsia that is thought to be a marker of disease process. The present study aimed to assess the diagnostic and predictive utility of urinary congophilia in pregnant women with hypertensive disorders of pregnancy as well as kidney diseases. Methods: This cohort study included 157 pregnant women, classified as healthy controls (n = 38), preeclampsia/eclampsia (n = 45), gestational hypertension (n = 9), chronic hypertension (n = 8), chronic kidney disease (CKD) (n = 27), and pregnancy-related acute kidney injury (PR-AKI) (n = 30). Urinary congophilia was assessed by Congo Red Dot Blot assay. Results: Congo red retention (CRR) values were significantly higher in women with preeclampsia/eclampsia (P ≤ 0.001), chronic hypertension (P = 0.029), gestational hypertension (P = 0.017), CKD (P ≤ 0.001), PR-AKI secondary to preeclampsia (P ≤ 0.001), and PR-AKI secondary to other causes (P = 0.001), compared with healthy controls. Women with preeclampsia, CKD, and PR-AKI (non-preeclampsia related) exhibited the highest levels of CRR. CRR positively correlated to proteinuria (P = 0.006) and serum creatinine (P = 0.027). CRR did not significantly vary between women who presented antepartum and those presented postpartum after removal of the placenta (P = 0.707). CRR at a cut-off point of at least 1.272 had 91% specificity and 61.1% sensitivity in predicting renal recovery in PR-AKI patients. CRR had a poor specificity in discriminating preeclampsia from the other clinical presentations. Conclusion: Urinary congophilia could not discriminate preeclampsia from similarly presenting kidney diseases in pregnancy. Further studies are needed to improve differentiation of these conditions.
Design, optimization, production and activity testing of recombinant immunotoxins expressed in plants and plant cells for the treatment of monocytic leukemia

ABSTRACT Antibody–drug conjugates (ADCs) can improve therapeutic indices compared to plain monoclonal antibodies (mAbs). However, ADC synthesis is complex because the components are produced separately in CHO cells (mAb) and often by chemical synthesis (drug). They are individually purified, coupled, and then the ADC is purified, increasing production costs compared to regular mAbs. In contrast, it is easier to produce recombinant fusion proteins consisting of an antibody derivative, linker and proteinaceous toxin, i.e. a recombinant immunotoxin (RIT). Plants are capable of the post-translational modifications needed for functional antibodies and can also express active protein toxins such as the recombinant mistletoe lectin viscumin, which is not possible in prokaryotes and mammalian cells respectively. Here, we used Nicotiana benthamiana and N. tabacum plants as well as tobacco BY-2 cell-based plant cell packs (PCPs) to produce effective RITs targeting CD64 as required for the treatment of myelomonocytic leukemia. We compared RITs with different subcellular targeting signals, linkers, and proteinaceous toxins. The accumulation of selected candidates was improved to ~ 40 mg kg−1 wet biomass using a design of experiments approach, and corresponding proteins were isolated with a purity of ~ 80% using an optimized affinity chromatography method with an overall yield of ~ 84%. One anti-CD64 targeted viscumin-based drug candidate was characterized in terms of storage stability and cytotoxicity test in vitro using human myelomonocytic leukemia cell lines. We identified bottlenecks in the plant-based expression platform that require further improvement and assessed critical process parameters that should be considered during process development for plant-made RITs. Highlights Toxin type and domain sequence affect accumulation of recombinant immunotoxins. Transient expression in plant cell packs and intact plants correlates well. IC50 values of toxicity correlate with the cell surface receptor concentration