bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of US Food and Drug Administration new drug and biologic approvals, regulatory pathways, and review times, 1980–2022
Authors: Seoane-Vazquez Enrique , Rodriguez-Monguio Rosa , Powers John H. 
Published: February 2024

AbstractU.S. laws enacted since 1983 have aimed to enhance the development and marketing of new pharmaceutical products. We thoroughly characterized all new molecular entities, therapeutic biologics, and gene and cell therapies approved by the US Food and Drug Administration (FDA) during the period 1980–2022 in the context of these laws and regulations. Throughout the study period, the FDA approved 1355 new pharmaceutical products. The median FDA review time decreased from 26.6 months prior to the Prescription Drug User Fee Act (1992), which authorized the FDA to collect fees from drug companies to 9.9 months after the Food and Drug Administration Safety and Innovation Act (2012), which created new designations that eliminated the requirement for evidence of added therapeutic benefit for FDA expedited drug review. The greatest increase in approvals occurred in antineoplastic and immunomodulating drugs, biologics, and orphan drugs. More than half of new drug approvals benefited from regulatory designations and pathways that did not require addressing unmet medical needs or demonstrating therapeutic benefit over available alternatives. The legislative goal of bringing more drugs to the market faster has been achieved. Further studies are needed to determine the therapeutic value to patients of new drugs approved using expedited approval pathways.
Cross-regulation of Aps-promoters in Lacticaseibacillus paracasei by the PsdR response regulator in response to lantibiotics
Authors: Zhang Qian , Zúñiga Manuel , Alcántara Cristina , Wolf Diana , Mascher Thorsten , Revilla-Guarinos Ainhoa 
Published: February 2024

AbstractThe PsdRSAB and ApsRSAB detoxification modules, together with the antimicrobial peptides (AMPs)-resistance determinants Dlt system and MprF protein, play major roles in the response to AMPs in Lacticaseibacillus paracasei BL23. Sensitivity assays with a collection of mutants showed that the PsdAB ABC transporter and the Dlt system are the main subtilin resistance determinants. Quantification of the transcriptional response to subtilin indicate that this response is exclusively regulated by the two paralogous systems PsdRSAB and ApsRSAB. Remarkably, a cross-regulation of the derAB, mprF and dlt-operon genes—usually under control of ApsR—by PsdR in response to subtilin was unveiled. The high similarity of the predicted structures of both response regulators (RR), and of the RR-binding sites support this possibility, which we experimentally verified by protein-DNA binding studies. ApsR-P shows a preferential binding in the order PderA > Pdlt > PmprF > PpsdA. However, PsdR-P bound with similar apparent affinity constants to the four promoters. This supports the cross-regulation of derAB, mprF and the dlt-operon by PsdR. The possibility of cross-regulation at the level of RR-promoter interaction allows some regulatory overlap with two RRs controlling the expression of systems involved in maintenance of critical cell membrane functions in response to lantibiotics.
Implementation of high step-up power converter for fuel cell application with hybrid MPPT controller
Authors: Prashanth V. , Rafikiran Shaik , Hussaian Basha C. H. , Kumar Jinka Anil , Dhanamjayulu C. , Kotb Hossam , ELrashidi Ali 
Published: February 2024

AbstractAs of now, there are multiple types of renewable energy sources available in nature which are hydro, wind, tidal, and solar. Among all of that the solar energy source is used in many applications because of its features are low maitainence cost, less human power for handling, a clean source, more availability in nature, and reduced carbon emissions. However, the disadvantages of solar networks are continuously depending on the weather conditions, high complexity of the solar energy storage, and lots of installation place is required. So, in this work, the Proton Exchange Membrane Fuel Stack (PEMFS) is utilized for supplying the power to the local consumers. The merits of this fuel stack are high power density, ability to work at very less temperature values, efficient heat maintenance, and water management. Also, this fuel stack gives a quick startup response. The only demerit of PEMFS is excessive current production, plus very less output voltage. To optimize the current supply of the fuel stack, a Wide Input Operation Single Switch Boost Converter (WIOSSBC) circuit is placed across the fuel stack output to improve the load voltage profile. The advantages of the WIOSSBC are less current ripples, uniform voltage supply, plus good voltage conversion ratio. Another issue of the fuel stack is nonlinear power production. To linearize the issue of fuel stack, the Grey Wolf Algorithm Dependent Fuzzy Logic Methodology (GWADFLM) is introduced in this article for maintaining the operating point of the fuel cell near to Maximum Power Point (MPP) place. The entire system is investigated by utilizing the MATLAB software.
VagiBIOM Lactobacillus suppository improves vaginal health index in perimenopausal women with bacterial vaginosis: a randomized control trial
Authors: Vivekanandan Vijitha , Khan Zaiba Hasan , Venugopal Giriprasad , Musunuru Bhavana , Mishra Priyanka , Srivastava Shalini , Ramadass Balamurugan , Subhadra Bobban 
Published: February 2024

AbstractBacterial vaginosis (BV) can cause vaginal dysbiosis that may influence general vaginal health and pregnancy complications. Balancing vaginal microbiome using Lactobacillus spp. may be a new way to prevent and treat mild BV. We conducted a randomized, double-blind, placebo-controlled pilot study aimed at evaluating the effect of the product VagiBIOM, a multi-Lactobacillus vaginal suppository, on peri- and premenopausal women with BV in restoring vaginal pH and overall vaginal health by resetting the vaginal microbiome composition. Sixty-six peri- and premenopausal women with BV symptoms were randomized with a 2:1 ratio to be treated with VagiBIOM or placebo suppositories. Vaginal pH, VAS itching score, total Nugent score, and vaginal health index (VHI) were measured. Vaginal microbiome changes before and after the treatment were analyzed by 16S rRNA sequencing and bioinformatics analysis. After 4 weeks of intervention with VagiBIOM or a placebo, the mean score for vaginal pH, VAS itching, and total Nugent score was significantly decreased from the baseline. Compared to the baseline scores, the VHI scores improved significantly following 28-day intervention (p < 0.001). Our results revealed two Lactobacillus species, L. hamsteri, and L. helveticus, as indicator species occurring differentially in the VagiBIOM-treated group. Furthermore, the regression and species network analyses revealed significant bacterial associations after VagiBIOM treatment. Lactobacillus hamsteri was positively associated with the Nugent score and negatively associated with vaginal pH. L. iners and L. salivarius were positively and inversely associated with VHI. As is typical, Bacteroides fragilis was positively associated with vaginal pH and negatively associated with the Nugent score. Interestingly, the Lactobacillus spp. diversity improved after VagiBIOM treatment. The VagiBIOM suppository treatment for peri- and premenopausal women with BV significantly relieved vaginal itching by decreasing vaginal pH and Nugent scores and improving the overall VHI after 4 weeks’ intervention. This effect was primarily the result of VagiBIOM improving vaginal Lactobacillus diversity.Trial Registration ClinicalTrials.gov registration: NCT05060029, first registration 09/28/2021: Title: A Pilot Study to Evaluate the Efficacy and Safety of Lactobacillus Species Suppositories on Vaginal Health and pH.
Comparative efficacy of different growth hormone supplementation protocols in improving clinical outcomes in women with poor ovarian response undergoing assisted reproductive therapy: a network meta-analysis
Authors: Xu Zheyun , Tong Weiquan , Yang Ze , Zhang Hongyan , Chen Xingbei 
Published: February 2024

AbstractGrowth hormone (GH) has a long-standing history of use as an adjunctive therapy in the treatment of poor ovarian response (POR), but the optimal dosage and timing remains unclear. The aim of this study was to evaluate and compare the efficacy of different GH supplementation protocols through a network meta-analysis (NMA) and determine the optimal treatment protocol. This study was reported based on the Preferred Reporting Items for Systematic Reviews for Network Meta-Analysis (PRISMA-NMA) statement. Databases including PubMed, Web of Science, Cochrane Library and Embase were searched until June 2023. A total of 524 records were retrieved in our search, and 23 clinical studies comprising 4889 cycles were involved. Seven different GH protocols were identified. Results showed that compared to the control group, daily administration of 4–8 IU of GH during the follicular phase of the stimulation cycle had the best comprehensive therapeutic effects on improving the number of retrieved oocytes, mature oocytes, endometrial thickness, and reducing gonadotropin requirements in POR patients undergoing assisted reproductive therapy, with a relatively brief treatment duration and a moderate total GH dose. Subgroup analysis demonstrated that this protocol could significantly improve the clinical pregnancy rate of POR patients in the randomized controlled trials (RCT) subgroup and the African subgroup. Therefore, its clinical application is suggested. Besides, the potential advantages of long-term GH supplementation protocol (using GH for at least 2 weeks before oocyte retrieval) has merit for further research. Rigorous and well-designed multi-arm RCTs are needed in the future to confirm the conclusions drawn from this study.
Environmental enrichments and data-driven welfare indicators for sheltered dogs using telemetric physiological measures and signal processing
Authors: Travain Tiziano , Lazebnik Teddy , Zamansky Anna , Cafazzo Simona , Valsecchi Paola , Natoli Eugenia 
Published: February 2024

AbstractShelters are stressful environments for domestic dogs which are known to negatively impact their welfare. The introduction of outside stimuli for dogs in this environment can improve their welfare and life conditions. However, our current understanding of the influence of different stimuli on shelter dogs’ welfare is limited and the data is still insufficient to draw conclusions. In this study, we collected 28 days (four weeks) of telemetry data from eight male dogs housed in an Italian shelter for a long period of time. During this period, three types of enrichment were introduced into the dogs’ pens for one week each: entertaining objects, intraspecific, and interspecific social enrichment, by means of the presence of female conspecifics and the presence of a human. To quantify their impact, we introduce novel metrics as indicators of sheltered dogs’ welfare based on telemetry data: the variation of heart rate, muscle activity, and body temperature from an average baseline day, quality of sleep, and the regularity for cyclicity of the aforementioned parameters, based on the day-night cycle. Using these metrics, we show that while all three stimuli statistically improve the dogs’ welfare, the variance between individual dogs is large. Moreover, our findings indicate that the presence of female conspecific is the best stimulus among the three explored options which improves both the quality of sleep and the parameters’ cyclicity. Our results are consistent with previous research findings while providing novel data-driven welfare indicators that promote objectivity. Thus, this research provides some useful guidelines for managing shelters and improving dogs’ welfare.
Montelukast, an available and safe anti-asthmatic drug, prevents maladaptive remodelling and maintains cardiac functionality following myocardial infarction
Authors: Muluhie Majeda , Castiglioni Laura , Rzemieniec Joanna , Mercuriali Benedetta , Gelosa Paolo , Sironi Luigi 
Published: February 2024

AbstractPreclinical and clinical data indicate that the 5-lipoxygenase pathway becomes activated in cardiovascular diseases suggesting an important role of CysLTs in atherosclerosis and in its ischemic complications. This study aims to investigate the effects of montelukast, a CysLTR-1 antagonist, in a mouse model of myocardial infarction (MI). C57BL/6N female mice were subjected to coronary artery ligation and received montelukast (10 mg/kg/day, intraperitoneal) or vehicle. Montelukast exerted beneficial effects in the infarcted area, decreasing mRNA expression of inflammatory genes, such Il1β and Ccl2 (p < 0.05), at 48 h after MI, and reducing infarct size and preventing ischemic wall thinning (p < 0.05) at 4 weeks. Furthermore, montelukast counteracted maladaptive remodelling of whole heart. Indeed, montelukast reduced LV mass (p < 0.05) and remote wall thickening (p < 0.05), and improved cardiac pumping function, as evidenced by increased global ejection fraction (p < 0.01), and regional contractility in infarcted (p < 0.05) and in remote non-infarcted (p < 0.05) myocardium. Finally, montelukast prevented cardiomyocytes hypertrophy (p < 0.05) in remote myocardium, reducing the phosphorylation of GSK3β, a regulator of hypertrophic pathway (p < 0.05). Our data strongly demonstrate the ability of montelukast to contrast the MI-induced maladaptive conditions, thus sustaining cardiac contractility. The results provide evidences for montelukast “repurposing” in cardiovascular diseases and in particular in myocardial infarction.
Quantitative probability estimation of light-induced inactivation of SARS-CoV-2
Authors: Quintana Jaime , Alda Irene , Alda Javier 
Published: February 2024

AbstractDuring the COVID pandemic caused by the SARS-CoV-2 virus, studies have shown the efficiency of deactivating this virus via ultraviolet light. The damage mechanism is well understood: UV light disturbs the integrity of the RNA chain at those locations where specific nucleotide neighbors occur. In this contribution, we present a model to address certain gaps in the description of the interaction between UV photons and the RNA sequence for virus inactivation. We begin by exploiting the available information on the pathogen’s morphology, physical, and genomic characteristics, enabling us to estimate the average number of UV photons required to photochemically damage the virus’s RNA. To generalize our results, we have numerically generated random RNA sequences and checked that the distribution of pairs of nucleotides susceptible of damage for the SARS-CoV-2 is within the expected values for a random-generated RNA chain. After determining the average number of photons reaching the RNA for a preset level of fluence (or photon density), we applied the binomial probability distribution to evaluate the damage of nucleotide pairs in the RNA chain due to UV radiation. Our results describe this interaction in terms of the probability of damaging a single pair of nucleotides, and the number of available photons. The cumulative probability exhibits a steep sigmoidal shape, implying that a relatively small change in the number of affected pairs may trigger the inactivation of the virus. Our light-RNA interaction model quantitatively describes how the fraction of affected pairs of nucleotides in the RNA sequence depends on the probability of damaging a single pair and the number of photons impinging on it. A better understanding of the underlying inactivation mechanism would help in the design of optimum experiments and UV sanitization methods. Although this paper focuses on SARS-CoV-2, these results can be adapted for any other type of pathogen susceptible of UV damage.
Comparative study on measurements of radiochromic films using portable colorimeters
Authors: Yasuda Hiroshi , Morioka Shido 
Published: February 2024

AbstractThe recently proposed method for on-site radiation dosimetry by a combination of radiochromic film and portable colorimeter was tested for six combinations of two popular Gafchromic films (EBT3 and EBT-XD) and three commercially available portable colorimeters (nix pro2, nix spectro2 and Spectro1 Pro; abbreviated to “NixP”, “NixS” and “SpoP”, respectively). EBT3 and EBT-XD were irradiated with X-rays (160 kV, 6.3 mA) up to 40 Gy and 80 Gy, respectively, and the radiation-induced color levels of RGB and CMYK components were measured with the three colorimeters. Angle dependence was examined by reading at 15° intervals. As a result, it was judged that all combinations would work effectively under certain irradiation conditions. NixP and NixS were applicable to a wider dose range for both films, while SpoP fit a lower dose range. On the other hand, SpoP showed an advantageous feature of no angular dependence in reading films, while NixP and NixS showed significant angle-dependent changes. These differences are considered to be attributable to the different geometries of LED light emission, which came from all directions (360°) in SpoP, 4 directions in NixP, and 8 directions in NixS. These findings are expected to expand the applicability of the novel method to various occasions of on-site dosimetry.
An economic feasibility assessment of implementing photovoltaic module reflectors under Malaysian meteorological conditions
Authors: Sultan Sakhr M. , Abdullah M. Z. , Tso C. P. , Abllah N. F. Nik , Zakaria N. , Ajeel Raheem K. , Sobayel K. 
Published: February 2024

AbstractThe use of a reflector can increase the solar radiation on the photovoltaic module (PV) surface, whereby the energy output can be improved. However, the economic feasibility may need to be considered too. This study is conducted, for the first time, due to the lack of studies regarding the economic feasibility assessment of implementing reflectors under the Malaysian meteorological conditions. The outcome will give information about the suitability for implementing a PV reflector in Malaysia through an experimental setup at a sewage treatment site, for two months in 2022. The Malaysian meteorological data, which include daily solar radiation, ambient temperature and wind velocity, were collected to study the output energy, efficiency and the economic perspective of a PV. In February 2022, the PV was operating without a reflector and the averaged values for the monthly solar radiation, ambient temperature and wind velocity were 539.9 MJ/m2, 28.4 °C and 2.2 m/s, respectively, which resulted in an output energy of 106.43 kWh. On the other hand, for April 2022, the PV was operating with a reflector. With the respective averaged input parameters 544.98 MJ/m2, 28.9 °C and 1.51 m/s, the output energy was 121.94 kWh. It is thus shown that the PV with a reflector increases the PV’s output energy by 14.57%. Also, it is shown that the cost-effective factor value is 0.955 which means that the PV reflector is economically feasible to be implemented under the Malaysian meteorological conditions. Hence, extensive research should be conducted to improve the performance of PV reflectors. The findings of this paper maybe useful for researchers and/or manufacturers of PV reflectors.
Emergent memory from tapping collisions in active granular matter
Authors: Caprini Lorenzo , Ldov Anton , Gupta Rahul Kumar , Ellenberg Hendrik , Wittmann René , Löwen Hartmut , Scholz Christian 
Published: February 2024

AbstractIn an equilibrium thermal environment, random elastic collisions between background particles and a tracer establish the picture of Brownian motion fulfilling the celebrated Einstein relation between diffusivity and mobility. However, extensions of the Einstein relation to link dissipation, fluctuations, and nonequilibrium dynamical mechanisms in active matter systems are still debated. Here, we investigate experimentally the impact of an active background on a passive tracer using vibrationally excited active particles, that result in multiple correlated tapping collisions with the tracer, for which a persistent memory emerges in the dynamics. The system is described by a generalized active Einstein relation that constrains fluctuations, dissipation, and effective activity, by taking the emerging tracer memory into account. Since the resulting persistence can largely be tuned by the environmental density and motility, our findings can be useful to engineer properties of various active systems in biomedical applications, microfluidics, chemical engineering, or swarm robotics.
Validating superior electrochemical properties of Ti3C2 MXene for supercapacitor applications through first-principles calculations
Authors: Irfan Sheheera , Haleem Yasir A. , Usman Muhammad , Ahmad Naseeb , Arshad Muhammad , Irshad Muhammad Imran , Saleem Muhammad Farooq , Habib Muhammad , Khan Rashid , Altin Serdar 
Published: February 2024

This work investigates the performance of Ti3C2 MXene for supercapacitor applications and validated its efficacy as an electrode material utilizing first-principles calculations.
Zero-polarization candidate regions for the calibration of wide-field optical polarimeters
Authors: Mandarakas N. , Panopoulou G. V. , Pelgrims V. , Potter S. B. , Pavlidou V. , Ramaprakash A. , Tassis K. , Blinov D. , Kiehlmann S. , Koutsiona E. , Maharana S. , Romanopoulos S. , Skalidis R. , Vervelaki A. , Clark S. E. , Kypriotakis J. A. , Readhead A. C. S. 
Published: February 2024

Context. The calibration of optical polarimeters relies on the use of stars with negligible polarization (i.e., unpolarized standard stars) for determining the instrumental polarization zero point. For wide-field polarimeters, calibration is often done by imaging the same star over multiple positions in the field of view (FoV), which is a time-consuming process. A more effective technique is to target fields containing multiple standard stars. While this method has been used for fields with highly polarized stars, there are no such sky regions with well measured unpolarized standard stars.
Aims. We aim to identify sky regions with tens of stars exhibiting negligible polarization that are suitable for a zero-point calibration of wide-field polarimeters.
Methods. We selected stars in regions with extremely low reddening, located at high Galactic latitudes. We targeted four ~40′ × 40′ fields in the northern and eight in the southern equatorial hemispheres. Observations were carried out at the Skinakas Observatory and the South African Astronomical Observatory.
Results. We found two fields in the north and seven in the south characterized by a mean polarization lower than p < 0.1%.
Conclusions. At least 9 out of the 12 fields can be used for a zero-point calibration of wide-field polarimeters.