bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing patient risk, benefit, and outcomes in drug development: A decade of ramucirumab clinical trials
Authors: Khan Adam , Khan Hassan , Hughes Griffin K. , Ladd Chase , McIntire Ryan , Gardner Brooke , Peña Andriana M. , Schoutko Abigail , Tuia Jordan , Minley Kirstien , Haslam Alyson , Prasad Vinay , Vassar Matt 
Published: May 2024

AbstractObjectiveThis study aims to evaluate published clinical trials of ramucirumab to assess the risk/benefit profile and burden over time for patients.BackgroundThe burden of oncologic drug development on patients paired with increasing clinical trial failure rates emphasizes the need for reform of drug development. Identifying and addressing patterns of excess burden can guide policy, ensure evidence‐based protections for trial participants, and improve medical decision‐making.MethodsOn May 25, 2023 a literature search was performed on Pubmed/MEDLINE, Embase, Cochrane CENTRAL, and ClinicalTrials.gov for clinical trials using ramucirumab as monotherapy or in combination with other interventions for cancer treatment. Authors screened titles and abstracts for potential inclusion in a masked, duplicate fashion. Following data screening, data was extracted in a masked, duplicate fashion. Trials were classified as positive when meeting their primary endpoint and safety, negative or indeterminate.ResultsRamucirumab was initially approved for gastric cancer but has since been tested in 20 cancers outside of its FDA approved indications. In our analysis of ramucirumab trials, there were a total of 10,936 participants and 10,303 adverse events reported. Gains in overall survival and progression‐free survival for patients were 1.5 and 1.2 months, respectively. FDA‐approved indications have reported more positive outcomes in comparison to off‐label indications.ConclusionWe found that FDA‐approved indications for ramucirumab had better efficacy outcomes than non‐approved indications. However, a concerning number of adverse events were observed across all trials assessed. Participants in ramucirumab randomized controlled trials saw meager gains in overall survival when evaluated against a comparison group. Clinicians should carefully weigh the risks associated with ramucirumab therapy given its toxicity burden and poor survival gains.
N‐Hydroxyalkanamide Based Organo/hydrogels as Novel Scaffolds for pH‐Dependent Metronidazole and Theophylline Release
Authors: Monika  , Meenakshi  , Brahma Mettle , Maruthi Mulaka , Selvakumar Sermadurai , Ansari Azaj , Gupta Manoj K. 
Published: May 2024

AbstractThe traditional delivery of metronidazole and theophylline presents challenges like bitter taste, variable absorption, and side effects. However, gel‐based systems offer advantages including enhanced targeted drug delivery, minimized side effects, and improved patient compliance, effectively addressing these challenges. Consequently, a cost‐effective synthesis of N‐hydroxyalkanamide gelators with varying alkyl chain lengths was achieved in a single‐step reaction procedure. These gelators formed self‐assembled aggregates in DMSO/water solvent system, resulting in organo/hydrogels at a minimum gelation concentration of 1.5 % w/v. Subsequently, metronidazole and theophylline were encapsulated within the gel core and released through gel‐to‐sol transition triggered by pH variation at 37 °C, while maintaining the structural‐activity relationship. UV‐vis spectroscopy was employed to observe the drug release behavior. Furthermore, in vitro cytotoxicity assays revealed cytotoxic effects against A549 lung adenocarcinoma cells, indicating anti‐proliferative activity against human lung cancer cells. Specifically, the gel containing theophylline (16HAD+Th) exhibited cytotoxicity on cancerous A549 cells with IC50 values of 19.23±0.6 μg/mL, followed by the gel containing metronidazole (16HAD+Mz) with IC50 values of 23.75±0.7 μg/mL. Moreover, the system demonstrated comparable antibacterial activity against both gram‐negative (E. coli) and gram‐positive bacteria (S. aureus).
Discovery of Novel Cholinesterase Inhibitors Easily Crossing the Blood‐Brain Barrier via Structure‐Property Relationship Investigation: Methylenedioxy‐Cinnamicamide Containing Tertiary Amine Side Chain
Authors: Shi Qing , Yang Zhi‐Yu , Wang Yi‐Hui , Yi Bi‐Xin , Gao Xiao‐Hui , Ding Yu‐Jie , Peng Dian , Chen Yan‐Ling , Liu Hao‐Ran 
Published: May 2024

AbstractIn the present investigation, a series of dimethoxy or methylenedioxy substituted‐cinnamamide derivatives containing tertiary amine moiety (N. N‐Dimethyl, N, N‐diethyl, Pyrrolidine, Piperidine, Morpholine) were synthesized and evaluated for cholinesterase inhibition and blood‐brain barrier (BBB) permeability. Although their chemical structures are similar, their biological activities exhibit diversity. The results showed that all compounds except for those containing morpholine group exhibited moderate to potent acetylcholinesterase inhibition. Preliminary screening of BBB permeability shows that methylenedioxy substituted compounds have better brain permeability than the others. Compound 10c, containing methylenedioxy and pyrrolidine side chain, showed a better acetylcholinesterase inhibition (IC50: 1.52±0.19 μmol/L) and good blood‐brain barrier permeability. Further pharmacokinetic investigation of compound 10c using ultra high performance liquid chromatography‐mass/mass spectrometry (UPLC‐MS/MS) in mice showed that compound 10c in brain tissue reached its peak concentration (857.72±93.56 ng/g) after dosing 30 min. Its half‐life in the serum is 331 min (5.52 h), and the CBrain/CSerum at various sampling points is ranged from 1.65 to 4.71(Mean: 2.76) within 24 hours. This investigation provides valuable information on the chemistry and pharmacological diversity of cinnamic acid derivatives and may be beneficial for the discovery of central nervous system drugs.
Percutaneous balloon mitral valvuloplasty with shockwave lithotripsy for the treatment of calcific mitral valve stenosis
Authors: Alnasser Sami M. , Moey Melissa , Ali Noman , Almazroa Loai , Al‐Shaibi Abdulaziz , Liauw Samantha , Claeys Mathias , Ong Geraldine , Fam Neil P. 
Published: May 2024

AbstractBackgroundCalcific mitral stenosis (calcific MS) presents a challenge for surgical treatment and is a contraindication for most contemporary transcatheter mitral valve replacement devices (TMVR), rendering patients with very limited therapeutic options.AimsThis study aims to assess the clinical and hemodynamic follow‐up after mitral valve lithotripsy (MVL).MethodsAll consecutive patients who underwent MVL to treat symptomatic calcific MS at St Michael's Hospital, Toronto, Canada, were included. Patients were deemed unsuitable for mitral surgery or TMVR after heart team assessment. Patients with rheumatic MS or ≥moderate mitral regurgitation (MR) were excluded. The primary endpoint was a reduction in the invasive mitral gradient by ≥50% without significant (≥moderate) MR.ResultsFifteen patients underwent MVL between 2021 and 2023 with a mean age of 74 ± 9 years; 53% were female, with a mean STS score of 10% ± 0.1%. Following MVL, there was a reduction in the invasively measured mean trans‐mitral gradient compared to baseline (14 mmHg vs. 6 mmHg; p < 0.05). The primary endpoint was achieved in 8 patients (53%) with no major procedural complications. At follow‐up (median 90 days, IQR 58‐115 days), 14 (93%) patients reported improved symptoms from New York Heart Association (NYHA) Class III–IV to NYHA Class I–II (p < 0.01) with stable echo‐derived mean gradient (7.7 mmHg ± 2 mmHg vs. 8.4 mmHg ± 2.9 mmHg (p = 0.7).ConclusionsIn selected patients with symptomatic inoperable calcific MS, MVL was safe and associated with significant short‐term clinical and hemodynamic improvement. MVL may represent a new compassionate therapy for this challenging cohort. Further studies are needed to determine the long‐term outcomes and help define the role of IVL technology in treating calcific valvular conditions.
Perianal tuberculosis presenting as a Fournier's gangrene
Authors: Lalanda Raquel , Barão Andreia , Draiblate Beatriz , Malcato Ester , Matos Hélder , Girão José , Rosa Rosário , Freire José Paulo , Miranda Luís 
Published: May 2024

Key Clinical MessageIn the setting of Fournier's gangrene, atypical clinical manifestations and complications in an immunocompetent patient warrant consideration of perineal tuberculosis as a potential underlying cause.AbstractTuberculosis cutis orificialis is a rare form of extrapulmonary tuberculosis that affects the perianal region. Fournier's gangrene is an aggressive necrotizing fasciitis that primarily involves the perianal area and external genitalia. A previously healthy 38‐year‐old man presented with a left perianal abscess. His condition deteriorated, leading to septic shock and multiorgan dysfunction syndrome. A CT scan displayed extensive necrotizing fasciitis. Treatment included broad‐spectrum antibiotics, numerous surgical perineal debridements, a transverse loop colostomy, and hyperbaric oxygen therapy. We believe the patient had pre‐existing asymptomatic, non‐diagnosed perianal tuberculosis, and a subsequent bacterial superinfection resulted in a perineal local abscess that progressed to severe Fournier's gangrene. The diagnosis of tuberculosis was confirmed through positive cultures and molecular identification in perineal biopsies. The patient experienced a complex clinical course with complications such as myocardial necrosis, acute respiratory distress syndrome, rhabdomyolysis with severe critical illness polyneuromyopathy and internal jugular thrombosis. Fournier's gangrene resulted in air dissection throughout the perineal fasciae, extending to the abdominal wall muscles resulting in an infected extraperitoneal spontaneous hematoma, probably caused by therapeutic anticoagulation. An extraperitoneal surgical drainage was performed. This case emphasizes the complexities in diagnosing and managing both perianal tuberculosis and Fournier's gangrene.
Unusual painful pelvic masses: Extramedullary hematopoiesis with extramedullary multiple myeloma
Authors: Cai Jennifer , Varda Marian , Sin David , Overby Halline , Yeh James J. 
Published: May 2024

Key Clinical MessageThe coexistence of extramedullary hematopoiesis and extramedullary multiple myeloma can occur and present as painful pelvic masses. In such a case, normal hematopoietic cells may outnumber clonal plasma cells, posing a diagnostic challenge.
Facile Preparation of Stable NiII‐ and CoII‐Tetraaminophthalocyanine Electropolymers for Highly Efficient Heterogeneous Carbon Dioxide Reduction
Authors: Luangchaiyaporn Jirapong , Chairat Permsak , Sodkhomkhum Rapheepraew , Sariciftci Niyazi Serdar , Thamyongkit Patchanita 
Published: May 2024

AbstractThis study focused on preparation of stable polymer films of NiII‐ and CoII‐tetraaminophthalocyanines, p‐NiTAPc and p‐CoTAPc, respectively, for highly efficient heterogeneous electrochemical carbon dioxide (CO2) reduction in a flow electrolysis cell. Major development represented in this work was fabrication of p‐NiTAPc and p‐CoTAPc films via electropolymerization of their corresponding monomers on carbon‐based substrates without using binder or conducting additive materials to obtain efficient gas diffusion electrodes (GDEs) for scalable, productive and selective CO2‐to‐CO conversion. The target polymers were characterized by UV‐visible spectrophotometry, attenuated total reflection‐Fourier transform infrared spectroscopy, scanning electron microscopy, energy dispersive X‐ray spectroscopy and cyclic voltammetry. According to controlled potential electrolysis and gas chromatography, p‐NiTAPc‐catalyzed CO2 reduction at −0.99 V vs. reversible hydrogen electrode (RHE) gave 953 mL of CO in a period of 16 hours with current density and Faradaic efficiency (FE) of 109±1 mA ⋅ cm−2 and 99±2 %, respectively. A p‐CoTAPc‐modified GDE exhibited superior catalytic performance to the case of p‐NiTAPc in terms of catalyst stability and CO productivity by performing the continuous CO2 reduction at the potential of −1.10 V vs. RHE for up to 41 hours and affording almost 3 times higher amount of CO with the current density of 161±5 mA⋅cm–2 and 95±2 % FE.
Chiral Induction in a Self‐Assembled Pd4 Coordination Cage with Chiral Guests
Authors: Singha Raghunath , Maity Pankaj , Samanta Dipak 
Published: May 2024

AbstractThe dynamic interplay of coordination bonds within metal‐organic cages offers a unique avenue for structural evolution in response to external stimuli, presenting a promising strategy for the construction of chiral assemblies. This adaptability is crucial for the selective synthesis of homochiral assemblies and advancement of asymmetric catalysis. In this study, we report the self‐assembly of an achiral square‐planar Pd(II) acceptor with a C2‐symmetric tetrapyridyl donor resulted in the formation of a racemic mixture of the chiral octahedral cage Pd4L2. The existence of this racemic mixture was confirmed using circular dichroism spectroscopy as well as single crystal X‐ray diffraction analysis. We encoded chiral information into the asymmetric cavity of the cage by encapsulating chiral aromatic guests through efficient π‐π stacking and hydrophobic interactions in aqueous media. The inclusion of a chiral guest induces a preference for one enantiomeric conformation of the cage over the other, effectively shifting the equilibrium towards a single, enantiopure host‐guest complex. While the concept of chiral guest recognition by a chiral host is well‐established, this work constitutes a remarkable example of guest‐mediated chirality transfer leading to the formation of a single enantiopure coordination complex from achiral building blocks.
Ring Fusion Elevates the Electronic Mobility of Azabenzannulated Perylene Diimide
Authors: Yang Fan , Wang Cui , Liang Laiyu , Wang Zhiqiang , You Xiaoxiao , Shao Guangwei , Wu Di , Xia Jianlong 
Published: May 2024

AbstractThe backwardness of n‐type organic semiconductors still exists compared with the p‐type counterparts. Thus, the development of high‐performance n‐type organic semiconductors is of great importance for organic electronic devices and their integrated circuits. In recent years, azabenzannulated perylene diimide (PDI), as one of immense bay‐region‐annulated PDI derivatives, has drawn considerable attentions. However, the electronic mobilities of azabenzannulated PDI derivatives are barely satisfactory. In this contribution, the peripheral benzene ring in azabenzannulated PDI 2 was fused to the ortho position by intramolecular C−H arylation cyclization. This endows the resultant azabenzannulated PDI 4 a planar configuration as well as electron deficient pentagonal ring. As a result, the electronic mobility of 4 is almost two orders of magnitude higher than that of the nonfused azabenzannulated PDI 2. This work shall pave a new avenue in elevating the performance of azabenzannulated PDI in organic electronics.
Controlling the Uptake and Release of Semiochemicals in Channel‐Type Metal‐Organic Frameworks Through Pore Expansion
Authors: Nicks Joshua , Shearer Greig C. , Paul‐Taylor Joseph , Lai‐Morrice James , Dadswell Chris , Guest Daniel , Hughes William O. H. , Spencer John , Düren Tina , Burrows Andrew D. 
Published: May 2024

AbstractSemiochemicals can be used to manipulate insect behaviour for sustainable pest management strategies, but their high volatility is a major issue for their practical implementation. Inclusion of these molecules within porous materials is a potential solution to this issue, as it can allow for a slower and more controlled release. In this work, we demonstrate that a series of Zr(IV) and Al(III) metal‐organic frameworks (MOFs) with channel‐type pores enable controlled release of three semiochemicals over 100 days by pore size design, with the uptake and rate of release highly dependent on the pore size. Insight from grand canonical Monte Carlo simulations indicates that this is due to weaker MOF‐guest interactions per guest molecule as the pore size increases. These MOFs are all stable post‐release and can be reloaded to show near‐identical re‐release profiles. These results provide valuable insight on the diffusion behaviour of volatile guests in MOFs, and for the further development of porous materials for sustainable agriculture applications.
Vibrational Circular Dichroism of a Chiral Triplet Nitrene Investigated Under Matrix‐Isolation Conditions in Parahydrogen
Authors: Beyer Frederike , Grassin Corentin , Rowen Julien F. , Sander Wolfram , Merten Christian 
Published: May 2024

AbstractVibrational circular dichroism (VCD) spectra of chiral high‐spin organic radicals are expected to show a strong intensity enhancement and are thought to be difficult to predict using state‐of‐the‐art theoretical methods. Herein we show that the chiral triplet nitrene obtained from photochemical cleavage of N2 from enantiopure 2‐azido‐9H‐fluorenol does not feature extraordinarily strong intensities and that the experimental spectra match nicely with calculated ones. Thereby, this study demonstrates the general feasibility of studies on chiral high‐spin organics by matrix‐isolation VCD.
Enantiomeric separation of tryptophan via novel chiral polyamide composite membrane
Authors: Peng Xinwei , Wei Yongming , Peng Yangfeng , Zhao Hongliang , Tong Tianzhong , He Quan 
Published: May 2024

AbstractThe separation of chiral drugs continues to pose a significant challenge. However, in recent years, the emergence of membrane‐based chiral separation has shown promising effectiveness due to its environmentally friendly, energy‐efficient, and cost‐effective characteristics. In this study, we prepared chiral composite membrane via interfacial polymerization (IP), utilizing β‐cyclodextrin (β‐CD) and piperazine (PIP) as mixed monomers in the aqueous phase. The chiral separation process was facilitated by β‐CD, serving as a chiral selective agent. The resulting membrane were characterized using SEM, FT‐IR, and XPS. Subsequently, the chiral separation performance of the membrane for DL‐tryptophan (Trp) was investigated. Lastly, the water flux, dye rejection, and stability of the membrane were also examined. The results showed that the optimized chiral PIP0.5β‐CD0.5 membrane achieved an enantiomeric excess percentage (ee%) of 43.0% for D‐Trp, with a solute flux of 66.18 nmol·cm−2·h−1, and maintained a good chiral separation stability. Additionally, the membrane demonstrated positive performance in the selective separation of mixed dyes, allowing for steady operation over a long period of time. This study offers fresh insights into membrane‐based chiral separations.
Wegner estimate and upper bound on the eigenvalue condition number of non‐Hermitian random matrices
Authors: Erdős László , Ji Hong Chang 
Published: May 2024

AbstractWe consider non‐Hermitian random matrices of the form , where is a general deterministic matrix and consists of independent entries with zero mean, unit variance, and bounded densities. For this ensemble, we prove (i) a Wegner estimate, that is, that the local density of eigenvalues is bounded by and (ii) that the expected condition number of any bulk eigenvalue is bounded by ; both results are optimal up to the factor . The latter result complements the very recent matching lower bound obtained by Cipolloni et al. and improves the ‐dependence of the upper bounds by Banks et al. and Jain et al. Our main ingredient, a near‐optimal lower tail estimate for the small singular values of , is of independent interest.
A comparison of procedures for evaluating and selecting alfalfa landrace germplasm for tolerance to salinity
Authors: Pecetti Luciano , Tlahig Samir , Confalonieri Massimo , Cornacchione Mónica V. , Hayek Taoufik , Angueira Salvador Prieto , Annicchiarico Paolo 
Published: May 2024

AbstractIn arid and semiarid regions, salinity may affect alfalfa (Medicago sativa) productivity and survival due to either cultivation on salt‐affected soils or the use of salinized irrigation water. Exploiting germplasm evolved under salt‐stress conditions offers opportunities for crop tolerance improvement. In the first phase of the current study, four reportedly salt‐tolerant landraces originated from stress‐prone areas of West Asia or North Africa and two reference commercial cultivars underwent three evaluation trials according to different methods, namely, seed germination in saline water, in vitro testing of young plants, and greenhouse evaluation of adult plants in Cone‐tainers. Experimental populations obtained by intercrossing landrace genotypes selected according to each evaluation method were subsequently evaluated under stressful field conditions in two regions featuring different salt stress type, namely, southern Tunisia (irrigation with saline water) and northwestern Argentina (rainfed cropping in saline soil). Landrace ranking for salt tolerance differed somewhat depending on the evaluation method, and the proportion of selected plants per landrace depended accordingly on the method. In each field experiment, there were two evaluation phases, and the second phase corresponded in both cases to harsher conditions. The in vitro evaluation and selection resulted in potentially more useful selected germplasm than the other evaluation methods. The field experiments highlighted the large specific adaptation effects that affected the response of salt‐tolerant germplasm across the two regions.
Input‐harmonic manipulated wideband high‐efficiency series of continuous mode power amplifier
Authors: Xuan Xuefei , Cheng Zhiqun , Zhang Zhiwei , Le Chao , Gong Tinwei 
Published: May 2024

SummaryIn this paper, a systematic research of the effects of second source harmonics caused by gate‐source capacitance in the design of a series of continuous mode (SCM) power amplifiers (PAs) is first presented. The research results show that, compared to the conventional SCMs that require the input second harmonic to be short circuited, SCMs under the impact of input nonlinearity have a more flexible input second harmonic manipulation space, and to further improve and maintain the performance of PAs in wideband operations, a new impedance design space is explored through analysis. For practical validation, SCMs PA considering the effects of the input nonlinearity is designed and fabricated with a 10‐W gallium nitride (GaN) device, acquiring 39.1–42 dBm output power and 60.6–71.5% drain efficiency (DE) performance at a 3 dB gain compression level operating over the 0.5–3.5 GHz frequency range with a relative bandwidth of 150%.
An overwinter protocol for detecting wolverines and other carnivores at camera traps paired with automated scent dispensers
Authors: Long Robert A. , MacKay Paula , Sauder Joel D. , Sinclair Mike , Aubry Keith B. , Raley Catherine M. 
Published: May 2024

AbstractCamera traps deployed with olfactory attractants are used to survey rare and elusive carnivores. Study areas with deep snowpack and rugged terrain present challenges and risks to field personnel, who traditionally must revisit camera stations regularly to refresh attractants. In such locations, alternative overwinter survey protocols that include a persistent attractant would improve both the safety and efficiency of camera‐trap surveys. We present a protocol for installing camera traps and automated scent dispensers on trees at above‐average maximum snow depth to eliminate the need for interim service visits and to enable standardized surveys to be conducted throughout the year. Our protocol proved to be effective at attracting and detecting numerous and repeated visits by wolverines, fishers, and other carnivores in two montane regions of the western contiguous United States. The volume, timing, and composition of liquid scent lure released by automated scent dispensers can be varied to target multiple species of interest, and the dispenser can be used in situations where bait rewards may influence the behavior of target species and/or pose human safety concerns.