bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of fall harvest time on forage yield and nutritive value of three alfalfa cultivars with different root types
Authors: Foster Allan , Vera Cecil L. , Malhi Sukhdev S. , Gill Kabal S. , Biligetu Bill
Published: October 2023

Warmer than normal late fall temperatures may change standard fall harvest management of alfalfa (Medicago sativa L.) in western Canada. The objective of this study was to evaluate the forage yield and nutritive value of three types of alfalfa cultivars under different harvest managements. A field experiment was conducted from 2013 to 2017 using rhizomatous type (RR), cv. AC Yellowhead (M. sativa subsp. falcata), tap root type (TR), cv. Equinox (ssp. sativa) and creeping root type (CR), cv. Spredor 4 alfalfa (ssp. sativa), at Melfort, SK, Canada. The five harvest treatments were two 1‐cut systems (early July or late July) and three 2‐cut systems (early July + early or late September, late July + late September). Total forage yield was greater in TR and CR alfalfa than RR alfalfa; however, RR alfalfa had higher total forage yield under dry growing conditions versus CR alfalfa. The three alfalfa cultivars had a similar response to 2‐cut harvest managements. The first cut yield was affected by the timing of the second cut of the previous year with the early September harvest reducing yield more than the late September. Three alfalfa cultivars had similar crude protein (CP), total digestible nutrient (TDN), and acid detergent fiber (ADF) concentrations. There was a significant nutrient yield benefit of TR and CR alfalfa under a 2‐cut system over the RR alfalfa. Although the prairie climate is warming, the findings suggest that a fall rest period until late September is recommended regardless of alfalfa types to maintain high hay yield over multiple years.
Retracted: Can the chemical industry solve the climate change?On the role of human energy production, renewable energies, and the potential of chemistry as a solution provider
Authors: Bertau Martin , Steiner Gerald
Published: October 2023

Climate change is typically attributed to the amount of greenhouse gases, such as carbon dioxide, in the atmosphere. Here we propose a different view, which takes into account the climate‐effecting gas concentration but recognizes human overpopulation and the associated energy production as the real underlying cause. For the chemical industry, there is a lever to change things by replacing existing processes with more efficient ones and by recovering low caloric heat. In this way, the chemical industry can play the role of a driver, a pioneer in the fight against climate change, which underlines the importance of the chemical industry in industrialized countries.
Exploiting the prediction of mass transfer performance in aerated coaxial mixers containing biopolymer solutions using empirical correlations and neural networks
Authors: Barros Paloma L. , Ein‐Mozaffari Farhad , Lohi Ali , Upreti Simant
Published: October 2023

The volumetric mass transfer coefficient is commonly used to assess the mixing effectiveness of gas–liquid bioreactor systems. Analyzing mass transfer performance in non‐Newtonian fluids inside coaxial mixers can be challenging due to the complex interaction between process variables, which requires developing robust characterization and estimation approaches. This study aims to investigate the gas dispersion in shear‐thinning biopolymers with yield stress using coaxial mixers in order to evaluate the effects of aeration and agitation on the volumetric mass transfer coefficient. A mixing configuration comprising a pitched blade turbine and an anchor was employed to disperse air into xanthan gum solutions, and the mass transfer performance was obtained at different impeller speeds and biopolymer concentrations by measuring the dissolved oxygen concentration. A dimensionless empirical correlation was proposed, and the results showed that the mass transfer was positively influenced by aeration intensity and agitation mechanism, quantified by the gas flow number and Reynolds number, respectively. Additionally, a strategy using stacking‐ensemble artificial neural networks was developed to accurately estimate the volumetric mass transfer coefficient, with a correlation coefficient of 0.998. The proposed mass transfer characterization approach overcame the complexities of analyzing aerated coaxial mixer systems and provided a reliable design model for bioreactor systems containing non‐Newtonian fluids.
A‐PGRD: Attention‐based automatic business process model generation from RPA process description
Authors: Zhu Rui , Liu Hang , Xu Xiaolong , Lin Leilei , Chen Yeting , Li Wenxin
Published: October 2023

Robotic process automation (RPA), a tool driven by business processes as the kernel, continues to heat up in the business community. However, process‐centric RPA modeling lacks an effective means. To address this problem, we propose a method for automatic process acquisition using RPA process descriptions as input. Existing deep learning process generation methods cannot be applied at the phrase level and have low accuracy at the sentence level. The proposed neural network method is based on an attention mechanism for automatic business process model generation from RPA process descriptions (A‐PGRD). The approach analyzes easily accessible and unstructured natural language text documents, constructs a non‐autoregressive neural network with an attention mechanism to retrieve the business process hierarchy, and generates a tree‐like business process graph using unsupervised automation. Through K‐fold cross‐validation, the method achieves an accuracy of 41.7% on the manually collected open‐source RPA business process dataset. Compared with the previous method, the method improves the learning efficiency by 23%–27%. The obtained results can be applied to the RPA tool to better optimize the business process and thus help organizations gain an edge over their competition.
Diffusion‐Ordered Spectroscopy (DOSY) as a Powerful NMR Method to Investigate Molecular Mobilities and Intermolecular Interactions in Complex Oil Mixtures
Authors: Yuan Meng , Xu Wenlong , Yang Ying , Li Suying , Yang Haiyan , Gao Jun , Jiang Heqing , Yang Menglong
Published: October 2023

Studying the characteristics and molecular mechanisms of liquid self‐diffusion coefficient and viscosity changes is of great significance for, e. g., chemical and petroleum processing. As examples of highly complex liquid,an asphaltene‐free high‐acid and high‐viscosity crude oil and its extracted fractions were studied by comparing their 1H DOSY diffusion maps. The crude oil exhibited a polydisperse diffusion distribution, including multiple diffusion portions with diffusion coefficients much smaller than that of any single fraction in independent diffusion. The main mechanism that leads to the decreases in the diffusion coefficients of crude oil is attributed to diffusion resistance enhanced by Dynamical Molecular‐Interaction Networks (DMINs), rather than by enlargement of the diffusion species caused by molecular aggregation. Constructed through the synergistic interactions of various polar molecules in crude oil, DMINs dynamically bind polar molecules, trap polarizable molecules, and spatially hinder the free motion of non‐polar molecules. Overall, this reduces the mobility of all molecular species, as illustrated by the decreased diffusion coefficients. This study demonstrates that DOSY is a powerful NMR method to investigate molecular motion abilities also in complex mixtures. In addition, the insights in the influence of the interaction matrix on the molecular mobility also help to understand the contribution of “structural viscosity” to the viscosity of heavy oil.
Release Kinetics of Potassium, Calcium, and Iron Cations from Carboxymethyl Cellulose Hydrogels at Different pH Values
Authors: Qu Yi , Haverkamp René , Jin Zhaorui , Jakobs‐Schönwandt Désirée , Patel Anant V. , Hellweg Thomas
Published: October 2023

In an in‐depth study of the mechanism of cation release from carboxymethyl cellulose hydrogels synthesized through Schiff base reaction, we analyze the differences in the release kinetics of potassium, calcium, and iron cations with Peleg model at pH values of pH 3.5 and pH 8.5 using ICP‐OES (inductively coupled plasma optical emission spectroscopy) technique.
High‐Content Screening of Synaptic Density Modulators in Primary Neuronal Cultures
Authors: Coulon Audrey , Siedlecki‐Wullich Dolores , Najdek Chloé , Gelle Carla , Ayral Anne‐Marie , Demiautte Florie , Lambert Erwan , Vandeputte Alexandre , Brodin Priscille , Mendes Tiago , Lambert Jean‐Charles , Kilinc Devrim , Dumont Julie , Chapuis Julien
Published: October 2023

The synapse, which represents the structural and functional basis of neuronal communication, is one of the first elements affected in several neurodegenerative diseases. To better understand the potential role of gene expression in synapse loss, we developed an original high‐content screening (HCS) model capable of quantitatively assessing the impact of gene silencing on synaptic density. Our approach is based on a model of primary neuronal cultures (PNCs) from the neonatal rat hippocampus, whose mature synapses are visualized by the relative localization of the presynaptic protein Synaptophysin with the postsynaptic protein Homer1. The heterogeneity of PNCs and the small sizes of the synaptic structures pose technical challenges associated with the level of automation necessary for HCS studies. We overcame these technical challenges, automated the processes of image analysis and data analysis, and carried out tests under real‐world conditions to demonstrate the robustness of the model developed. In this article, we describe the screening of a custom library of 198 shRNAs in PNCs in the 384‐well plate format. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.

Basic Protocol 1: Culture of primary hippocampal rat neurons in 384‐well plates

Basic Protocol 2: Lentiviral shRNA transduction of primary neuronal culture in 384‐well plates

Basic Protocol 3: Immunostaining of the neuronal network and synaptic markers in 384‐well plates

Basic Protocol 4: Image acquisition using a high‐throughput reader

Basic Protocol 5: Image segmentation and analysis

Basic Protocol 6: Synaptic density analysis
Improved Culture Methods for Human Coronaviruses HCoV‐OC43, HCoV‐229E, and HCoV‐NL63
Authors: Fausto Alejandra , Otter Clayton J. , Bracci Nicole , Weiss Susan R.
Published: October 2023

HCoV‐OC43, HCoV‐229E, HCoV‐NL63, and HCoV‐HKU1 are four of the seven known human coronaviruses (HCoVs) and, unlike the highly pathogenic SARS‐CoV, MERS‐CoV, and SARS‐CoV‐2, these four so‐called seasonal HCoVs generally cause mild upper‐respiratory‐tract illness. As Biosafety Level 2 (BSL‐2) pathogens, the seasonal HCoVs are more accessible and can be used as surrogates for studying the highly pathogenic HCoVs. However, scientists have for many years found these difficult to study because of the lack of a universal culture system and the inability of typical culture methods to yield high‐titer infectious stocks. We have developed assays to grow and quantify infectious virus and viral RNA for HCoV‐OC43, ‐229E, and ‐NL63. We identified which immortalized cell lines should be used to optimize the replication of HCoV‐OC43, ‐229E, and ‐NL63 in order to generate high titers (Vero E6, Huh‐7, and LLC‐MK2 cells, respectively). Here we present protocols for improved propagation and quantification of each seasonal HCoV. © 2023 Wiley Periodicals LLC.

Basic Protocol 1: Growth of HCoVs

Basic Protocol 2: Quantification of HCoV by plaque assay

Basic Protocol 3: Quantification of HCoV RNA products of replication

Basic Protocol 4: Concentrating HCoVs via ultracentrifugation

This article was corrected on 20 March 2024. See the end of the full text for details.
Ruptured cystic artery pseudoaneurysm after self‐expandable metal stent placement for malignant biliary obstruction
Authors: Mie Takafumi , Sasaki Takashi , Matsueda Kiyoshi , Okamoto Takeshi , Hirai Tatsuki , Ishitsuka Takahiro , Yamada Manabu , Nakagawa Hiroki , Furukawa Takaaki , Takeda Tsuyoshi , Kasuga Akiyoshi , Ozaka Masato , Sasahira Naoki
Published: October 2023

We report a case of ruptured cystic artery pseudoaneurysm after self‐expandable metal stent placement for malignant biliary obstruction. A 78‐year‐old woman on palliative care after chemotherapy for unresectable pancreatic head cancer presented with obstructive jaundice. Imaging revealed a dilated common bile duct and an enlarged gallbladder with cystic wall thickening. Endoscopic retrograde cholangiopancreatography was performed and a fully‐covered self‐expandable metal stent was placed in the bile duct, leading to resolution of jaundice. She presented with hematochezia 7 days later. Contrast‐enhanced computed tomography revealed a cystic artery pseudoaneurysm with extravasation of contrast into a blood‐filled gallbladder. Hemostasis was achieved after emergent transcatheter arterial embolization. Rupture of cystic artery pseudoaneurysm should be raised as a differential diagnosis for hemobilia after self‐expandable metal stent placement, particularly in cases accompanied by inflamed gallbladders.
One hundred and six years of change in a Sonoran Desert plant community: Impact of climate anomalies and trends in species sensitivities
Authors: Brown Charlotte , Rodriguez Buritica Susana , Goldberg Deborah E. , Reichenbacher Frank , Venable D. Lawrence , Webb Robert H. , Wilder Benjamin T.
Published: October 2023

A major restriction in predicting plant community response to future climate change is a lack of long‐term data needed to properly assess species and community response to climate and identify a baseline to detect climate anomalies. Here, we use a 106‐year dataset on a Sonoran Desert plant community to test the role of extreme temperature and precipitation anomalies on community dynamics at the decadal scale and over time. Additionally, we tested the climate sensitivity of 39 desert plant species and whether sensitivity was associated with growth form, longevity, geographic range, or local dominance. We found that desert plant communities had shifted directionally over the 106 years, but the climate had little influence on this directional change primarily due to nonlinear shifts in precipitation anomalies. Decadal‐scale climate had the largest impact on species richness, species relative density, and total plant cover, explaining up to 26%, 45%, and 55% of the variance in each, respectively. Drought and the interaction between the frequency of freeze events and above‐average summer precipitation were among the most influential climate factors. Increased drought frequency and wetter periods with frequent freeze events led to larger reductions in total plant cover, species richness, and the relative densities of dominant subshrubs Ambrosia deltoidea and Encelia farinosa. More than 80% of the tested species were sensitive to climate, but sensitivity was not associated with a species' local dominance, longevity, geographic range, or growth form. Some species appear to exhibit demographic buffering, where when they have a higher sensitivity to drought, they also tend to have a higher sensitivity to favorable (i.e., wetter and hotter) conditions. Overall, our results suggest that, while decadal‐scale climate variation substantially impacts these desert plant communities, directional change in temperature over the last century has had little impact due to the relative importance of precipitation and drought. With projections of increased drought in this region, we may see reductions in total vegetation cover and species richness due to the loss of species, possibly through a breakdown in their ability to demographically buffer climatic variation, potentially changing community dynamics through a change in facilitative and competitive processes.
The effect of gun buy‐back law reform on homicides and suicides in Australia
Authors: Duenow Patrick , Connelly Luke B.
Published: October 2023

In this paper we use the synthetic control method (SCM) to estimate the causal effects of a national legislative reform accompanied by mandatory gun buy‐backs in Australia on both suicide and homicide rates. Using a rich international dataset, we are able to separate not only these two death types, but also to distinguish deaths by firearm and by other means, thereby enabling us to test substitution‐of‐means hypotheses. Specifically, we apply the SCM to determine whether any reductions in firearm‐related death rates where wholly or partly offset by increases in the use of other means (e.g., bladed weapons, poisons) to commit suicides and perpetrate homicides. Our findings show that these gun control policies substantially reduced both homicides and suicides by firearm, but also some evidence of other‐means substitution.
Age‐related differences in hippocampal subfield volumes across the human lifespan: A meta‐analysis
Authors: Homayouni Roya , Canada Kelsey L. , Saifullah Samaah , Foster Da' Jonae , Thill Charlotte , Raz Naftali , Daugherty Ana M. , Ofen Noa
Published: October 2023

The human hippocampus (Hc) is critical for memory function across the lifespan. It is comprised of cytoarchitectonically distinct subfields: dentate gyrus (DG), cornu ammonis sectors (CA) 1‐4, and subiculum, each of which may be differentially susceptible to neurodevelopmental and neurodegenerative mechanisms. Identifying age‐related differences in Hc subfield volumes can provide insights into neural mechanisms of memory function across the lifespan. Limited evidence suggests that DG and CA3 volumes differ across development while other regions remain relatively stable, and studies of adulthood implicate a downward trend in all subfield volumes with prominent age effects on CA1. Due to differences in methods and limited sampling for any single study, the magnitude of age effects on Hc subfield volumes and their probable lifespan trajectories remain unclear. Here, we conducted a meta‐analysis on cross‐sectional studies (n = 48,278 participants, ages = 4–94 years) to examine the association between age and Hc subfield volumes in development (n = 11 studies), adulthood (n = 30 studies), and a combined lifespan sample (n = 41 studies) while adjusting estimates for sample sizes. In development, age was positively associated with DG and CA3‐4 volumes, whereas in adulthood a negative association was observed with all subfield volumes. Notably, the observed age effects were not different across subfield volumes within each age group. All subfield volumes showed a nonlinear age pattern across the lifespan with DG and CA3‐4 volumes showing a more distinct age trajectory as compared to the other subfields. Lastly, among all the study‐level variables, only female percentage of the study sample moderated the age effect on CA1 volume: a higher female‐to‐male ratio in the study sample was linked to the greater negative association between age and CA1 volume. These results document that Hc subfield volumes differ as a function of age offering broader implications for constructing theoretical models of lifespan memory development.
Hypochlorous acid in a double formulation (liquid plus gel) is a key prognostic factor for healing and absence of infection in chronic ulcers. A nonrandomized concurrent treatment study
Authors: Herruzo Rafael , Fondo Alvarez Erika , Herruzo Irene , Garrido‐Estepa Macarena , Santiso Casanova Emma , Cerame Perez Silvia
Published: October 2023

Background and Aims

Diverse protocols prevent infection and/or improve ulcer epithelialization. The existing protocols tend to antagonize the risk factors that promote the chronicity of this type of wound. Hypochlorous acid (HOCl) is used to treat ulcers and wounds because of its antiseptic and noncytotoxic properties. Its liquid form is effective but has little residual effect, while in gel it has more residual power.

Methods

An experimental nonrandomized study has been carried out treating 346 chronic ulcers of various etiologies in 220 patients. Ulcer outcomes were originally classified as: “complete healing,” “incomplete healing without infection,” and “incomplete healing with infection.” Various antiseptic solutions were used as ulcers cleaning solutions: liquid HOCl, gel HOCl, polymeric biguanide, or chlorhexidine. Only one was applied to the lesion as monotherapy. But, in other cases, we used a combined HOCl (liquid then gel: bitherapy). Bivariate (Chi‐square and variance tests) and multivariate studies (logistic regression) evaluated associations of ulcer characteristics and mono or bitherapy outcomes.

Results

Four factors reduce the probability of complete ulcer healing: patient age (odds ratio [OR]: 0.97); weeks of ulcer evolution (OR: 0.99); poor granulation on admission (OR: 0.35); and need for antibiotic therapy (OR: 0.41). One factor favored healing: combined HOCl therapy with liquid plus gel (OR: 4.8). Infections were associated with longer times of evolution (OR: 1.002) and bad odor of the ulcer on admission (OR: 14), but bitreatment with HOCl reduced the risk of infection (OR: 0.3).

Conclusion

A double HOCl formulation (liquid plus gel) reduces the probability of poor healing and infection, in chronic ulcers of various etiologies.
The variability of dual‐task walking parameters using in‐shoe inertial sensors in nonconcussed individuals: A randomized within‐subject repeated measures design
Authors: Mitchell Courtney , Cronin John
Published: October 2023

Background and Aims

There is a need for high utility and portability, and cost‐effective technologies that are suitable for assessing dual‐task gait after experiencing a concussion. Current technologies utilized such as 3D motion capture and force plates are too complex and expensive for most practitioners. The aim of this study was to quantify the variability of dual‐task walking gait parameters using in‐shoe inertial sensors in nonconcussed individuals.

Methods

This was a randomized within‐subject repeated measures design conducted within a sports laboratory. Twenty healthy, uninjured, nonconcussed participants were recruited for this study. Gait variables of interest were measured across three 2‐min continuous walking protocols (12 m, 30 m, 1 min out and back) while performing a cognitive task of counting backward in sevens from a randomly generated number between 300 and 500. Testing was completed over three occasions separated by 7 days, for a total of nine walking trials. Participants completed the testing protocols in a randomized, individual order. The primary outcome was to determine the variability of dual‐task walking gait parameters using in‐shoe inertial sensors in nonconcussed individuals across three protocols.

Results

Three to four participants were allocated to each randomized protocol order. Regarding the absolute consistency (coefficient of variation [CV]) between testing occasions, no gait measure was found to have variability above 6.5%. Relative consistency (intraclass correlation coefficient [ICC]) was acceptable (>0.70) in 95% of the variables of interest, with only three variables < 0.70. Similar variability was found across the three testing protocols.

Conclusion

In‐shoe inertial sensors provide a viable option for monitoring gait parameters. This technology is also reliable across different testing distances, thus offering various testing options for practitioners. Further research needs to be conducted to examine the variability with concussed subjects.
cyto‐Knet: An instance segmentation approach for multiple myeloma plasma cells using conditional kernels
Authors: Salvi Massimo , Michielli Nicola , Meiburger Kristen M. , Cattelino Cristina , Cotrufo Bruna , Giacosa Matteo , Giovanzana Chiara , Molinari Filippo
Published: October 2023

Multiple myeloma disrupts normal blood cell production, requiring early detection due to the increased risk of bone metastases. Although various artificial intelligence (AI) methods have been developed to assist pathologists, they often lack comprehensive metrics to measure both detection and segmentation errors. This study presents a hybrid framework that combines deep learning and heuristic techniques to achieve accurate instance segmentation of individual plasma cells in Giemsa‐stained cytology images. Our proposed network, called cyto‐Knet, incorporates an innovative color‐balancing method as a preprocessing step to standardize the appearance of cytological images. Our network leverages a 4‐class segmentation strategy with conditional kernels to enhance segmentation performance and accuracy. Additionally, a marker‐based watershed algorithm is employed in the postprocessing step to address the challenge of merged objects. Extensive validation at both pixel and object‐based levels demonstrates superior performance compared with state‐of‐the‐art techniques. Our method achieves pixel‐based metrics (precision, recall, and F1‐score) of approximately 0.90. The object‐based evaluation reveals an average Dice coefficient of 0.9130 and an aggregated Jaccard index of 0.8237. Importantly, our solution is designed for integration into an end‐to‐end system for diagnosis support and can be easily extended to other applications.
SRP&PASMLP‐Net: Lightweight skin lesion segmentation network based on structural re‐parameterization and parallel axial shift multilayer perceptron
Authors: Wei Shuning , Chen Haijun , Zhao Junqi , Zhou Ying , Yang Yimei
Published: October 2023

Accurate skin lesion segmentation (SLS) plays an essential role in the computer‐aided diagnosis of skin diseases, for example, melanomas. However, the automated SLS is challenging due to variations in the nature of skin diseases, particularly the ambiguities of boundaries of skin lesion areas (SLAs) and occlusions by hairs. Though many deep learning models, represented by UNet, have been successfully applied to the SLS over the past years, most suffer from inaccurate SLA segmentation with heavy model parameters and slow inferencing speed, hindering their practical applications. To address these challenges, a lightweight SLS network based on structural re‐parameterization and parallel axial shift multilayer perceptron (MLP), called SRP&PASMLP‐Net, is proposed to achieve powerful segmentation performance with fast inference ability. Specifically, a kind of diverse convolution module, the Re‐parameterization Diversity Convolution (RDC) block, is proposed in the shallow stage of the segmentation network to enrich the feature space. The inference is performed by structural re‐parameterization techniques to decouple the structure at the training and inference stages, thus improving the performance of the model without any inference time cost. In addition, a parallel axial shift MLP (PASMLP) module is proposed, which captures local dependencies by axially shifting the channels of the feature map to capture the information flow from different axes and reduce the network parameters and computational complexity effectively. Extensive experimental results show that the proposed SRP&PASMLP‐Net can provide a 4‐fold improvement in the inference speed and a 17‐fold reduction in model parameters compared with the benchmark network, UNet. It outperforms the state‐of‐the‐art methods on two public datasets, that is, ISIC2018 and PH2, for the SLS.
Growth Factors in Nutritional Support
Authors: Hatton Jimmi , Luer Mark S. , Rapp Robert P.
Published: October 2023

Protein catabolism occurs in the severely stressed patient despite adequate protein supplementation. Supplementation of endogenous growth factors is one mechanism being evaluated to promote anabolism and improve nitrogen retention. Recombinant technology has provided a means to reproduce these endogenous growth factors. Both recombinant human growth hormone (rGH) and recombinant human insulin‐like growth factor‐1 (rhIGf‐1) are undergoing clinical trials to establish their roles in nutritional support.
Assessing the Treatment of Congestive Heart Failure: Diuretics, Vasodilators, and Angiotensin‐Converting Enzyme Inhibitors
Authors: Chow Moses S.S.
Published: October 2023

Congestive heart failure (CHF) causes disabling symptoms and increases the likelihood of decreased survival. Diuretics, direct vasodilators, and angiotensin‐converting enzyme (ACE) inhibitors can be used to reduce symptoms, prolong life, or both, in these individuals. Diuretics induce sodium and water excretion, leading to decreased cardiac preload and wall tension, and an effective decrease of symptomatic pulmonary and systemic congestion. They have not yet been shown to prolong life in patients with CHF, however. Direct vasodilators, which induce venodilation, arterial dilation, or both (balanced vasodilators), may improve symptoms, and some but not all prolong life. Venodilators, such as nitrates, exert a venous pooling effect, decreasing cardiac preload and symptoms of congestion. Arterial dilators, such as hydralazine, decrease afterload and improve cardiac output. The combination of hydralazine and isosorbide dinitrate provides balanced vasodilation. It also improves survival, but is associated with a relatively high frequency of side effects necessitating discontinuation of one or both agents. The drugs are not approved by the Food and Drug Administration for the treatment of heart failure. Flosequinan, a new orally administered, long‐acting, balanced arteriovenous dilator, improves exercise tolerance and symptoms. However, preliminary analysis of data from a large, multicenter trial revealed increased mortality and hospitalization for worsening CHF. The drug has recently been withdrawn from the market. The ACE inhibitors can cause hemodynamic and neurohormonal changes that lead to a reduction of preload and afterload, decreasing symptoms of heart failure. They significantly decrease CHF mortality, and might also deter the development of overt heart failure in some asymptomatic patients with left ventricular dysfunction.
Assessing the Treatment of Congestive Heart Failure: Inotropic Agents and Calcium Channel Blockers
Authors: Hilleman Daniel E.
Published: October 2023

Despite recent evidence that angiotensin‐converting enzyme (ACE) inhibitors reduce mortality in patients with congestive heart failure (CHF), it is important to note that roughly 40% of patients with New York Heart Association class I—III disease treated with these agents died during 4‐year follow‐up in the treatment arm of two large trials. Given this high mortality rate, there is an obvious need for therapy beyond digoxin, diuretics, and ACE inhibitors. Digoxin is associated with favorable effects on exercise capacity, ejection fraction, and clinical symptomatology in the majority of patients with CHF. Its effects on mortality are unknown, but are the subject of a continuing trial sponsored by the National Institutes of Health. The β‐agonists are also associated with hemodynamic and clinical improvements in patients with CHF, but probably increase the risk of mortality, especially when taken on a long‐term basis. Therefore, their use should be limited to the short‐term management of acute exacerbations of CHF. Phosphodiesterase inhibitors, particularly milrinone, are associated with increased mortality in patients with CHF, apparently related to their arrhythmogenic effect. Little evidence exists that calcium channel blockers exert beneficial effects in patients with CHF (unlike their role in hypertrophic cardiomyopathy); indeed, first‐generation calcium channel blockers may be detrimental in patients with left ventricular dysfunction and they should generally be avoided in this setting. Treatment of ischemia in patients with CHF should be initiated with nitrates; low dosages of vasoselective dihydropyridine calcium channel blockers may be attempted if nitrates fail.
Comparison of Quantitative Methods to Assess Hepatic Function: Pugh's Classification, Indocyanine Green, Antipyrine, and Dextromethorphan
Authors: Figg William D. , Dukes George E. , Lesesne Henry R. , Carson Stanley W. , Songer Stephen S. , Pritchard J. Fred , Hermann David J. , Powell J. Robert , Hak Lawrence J.
Published: October 2023

Study Objectives. To compare three quantitative metabolic markers used to assess hepatic function, indocyanine green (ICG), a high‐extraction marker; antipyrine, a low‐extraction marker; and dextromethorphan, a P‐450IID6 marker, with the clinically used Pugh's classification.

Design. Comparison of 12 healthy controls with 12 age‐ and sex‐matched patients with different degrees of liver disease.

Setting. Research center in a university‐affiliated teaching hospital.

Patients. The 12 patients had different degrees of liver disease: 4 mild (Pugh's score 6 or 7); 4 moderate (Pugh's score 8 or 9); and 4 severe (Pugh's score ≥ 10). Each level had an equal number of men and women subjects.

Measurements and Main Results. Clearance of ICG detected mild alterations in hepatic function as efficiently as it did for moderate and severe impairment, but it lacked the specificity to distinguish among the classification groups. In contrast, antipyrine was effective in identifying moderate and severe hepatic impairment; however, its clearance was not reduced in mild liver disease. Pugh's classification appears to be a clinically useful method of assessing the global degree of hepatic impairment in patients with chronic disease, and there was a significant correlation between it and antipyrine clearance (r=0.67, p=0.0003) and ICG clearance (r=0.86, p=0.0001). Four of eight patients with a Pugh's score greater than 8 had a dextromethorphan metabolic ratio expression reflective of a poor metabolizer phenotype based on 0‐ to 4‐hour urine collection, but only two of those eight patients were classified as poor metabolizers based on 4‐ to 12‐hour urine collection. These percentages of poor metabolizers are substantially higher than for historical controls (8.5–10.4%) and most likely reflect a decrease in the P‐450IID6 functional ability with progression of liver disease. However, due to small sample size and lack of knowledge of the patients' genotypes, these data are only suggestive.

Conclusion. Pugh's classification appears to be a reliable indicator of the degree of chronic liver disease and could be employed as a drug development research classification tool; however, it does not replace quantitative metabolic markers, especially isozyme‐specific markers.
The Refeeding Syndrome: An Approach to Understanding Its Complications and Preventing Its Occurrence
Authors: Brooks Marta J. , Melnik George
Published: October 2023

The refeeding syndrome (RS) is a complication of nutritional support that potentially causes considerable morbidity and mortality. Compensatory metabolic alterations secondary to chronic starvation predispose malnourished patients to RS. Providing nutritional support initiates an intracellular shift of potassium, magnesium, and phosphate that results in many adverse effects. The literature addressing RS focuses on only one electrolyte abnormality, hypophosphatemia; however, often all three electrolyte levels are perturbed. Thus RS should be characterized as a syndrome of generalized fluid and electrolyte imbalance. Recommended electrolyte supplementation and laboratory monitoring can help prevent the disorder in susceptible patients.
A Retrospective Study of Sodium Nitroprusside Use and Assessment of the Potential Risk of Cyanide Poisoning
Authors: Johanning Rebecca J. , Zaske Darwin E. , Tschida Suzanne J. , Johnson Steven V. , Hoey Lori L. , Vance‐Bryan Kyle
Published: October 2023

Sodium nitroprusside (SNP) is an effective vasodilator but is potentially dangerous due to its cyanide content. Infusion rates above 2 μg/kg/minute may cause cyanide to accumulate to toxic concentrations in critically ill patients. Coadministration of thiosulfate with SNP effectively and safely prevents cyanide toxicity. This study determined if patients at our institution were treated with SNP infusion rates that could cause cyanide toxicity and whether those patients were administered thiosulfate. We reviewed the charts of 36 critically ill patients treated with SNP during the previous 12 months. In 72% of patients the SNP infusion rates were above 2 μg/kg/minute. In 47% the rates were greater than 2 μg/kg/minute for 6 hours or more, and in 20% they were greater than 5 μg/kg/minute for up to 11 hours. None of the patients was administered thiosulfate. In a significant number of patients the infusion rates of SNP potentially exposed them to significant risk of cyanide toxicity including death.
Pharmacoeconomic Issues in the Treatment of Depression
Authors: Saklad Stephen R.
Published: October 2023

The advent of newer, more expensive antidepressant agents in the past decade has focused renewed attention on major depressive disorder. The higher costs associated with purchasing the drugs makes their use appear to increase the cost of treating depression. Pharmacoeconomic methods are means of measuring the related advantages and costs, and provide guidance in drug selection. When such measures have been applied, the initial impression of increased costs for treating depressed persons with these agents is not supported. Pharmacoeconomic studies show that the newer antidepressants have clinically significant advantages that translate into lower total health system costs for treating major depressive disorder.
Antidepressant Drug Interactions and the Cytochrome P450 System: A Critical Appraisal
Authors: Riesenman Cara
Published: October 2023

Evaluation of the inhibitory effects of antidepressant drugs on hepatic cytochrome P450 isoenzymes can allow clinicians to predict drug interactions occurring via this mechanism a priori. The magnitude and clinical relevance of these drug interactions are dependent on many factors including concentration of the isoenzyme inhibitor, contribution of active metabolites with isoenzyme inhibitory activity, and toxicity of the concomitant medication. This review summarizes information to date regarding the inhibitory potency of fluoxetine, fluvoxamine, paroxetine, sertraline, nefazodone, and venlafaxine on five isoenzyme systems: CYP2D6, CYP3A3/4, CYP1A2, CYP2C9, and CYP2C19. Both in vitro and in vivo isoenzyme inhibition data are presented and correlated to drug interactions of clinical relevance.
Association of Vancomycin Serum Concentrations With Outcomes in Patients With Gram‐Positive Bacteremia
Authors: Zimmermann Anthony E. , Katona Brian G. , Plaisance Karen I.
Published: October 2023

We attempted to determine if an association exists between vancomycin serum concentrations resulting from traditional dosing regimens, and efficacy and toxicity outcomes. We reviewed the medical charts of 273 consecutive patients prescribed 273 courses of vancomycin therapy for documented, gram‐positive bacteremia. Of the 273 courses of therapy, 45 and 31 patients met all criteria and were evaluated for toxicity and efficacy, respectively. The duration of fever and abnormal white blood cell counts, length of hospital stay, overall mortality, serum creatinine, and serum vancomycin concentrations were evaluated retrospectively. No association between initial peak or trough levels with mortality was noted. However, patients were more likely to become afebrile within 72 hours if peak and trough concentrations were 20 μg/ml or greater and 10 μg/ml or greater, respectively (p<0.01). Patients were also more likely to have their white blood cell count return to normal within 72 hours if trough concentrations were 10 μg/ml or above (p<0.01). No statistically significant correlation between nephrotoxicity and initial serum creatinine, days of hospital stay, or days of vancomycin therapy were found. Serum concentrations of vancomycin, assessed before the development of nephrotoxicity, were significantly higher in patients who became nephrotoxic. Mean (SD) trough concentrations were 23.2 (2.5) μg/ml and 10.2 (3.8) μg/ml in nephrotoxic and nonnephrotoxic patients, respectively. Our results suggest that the commonly accepted therapeutic range for vancomycin trough concentrations (<10 μg/ml) may be too restrictive in patients receiving vancomycin therapy alone.
Nursing Home‐Acquired Pneumonia: Outcomes from a Clinical Process Improvement Program
Authors: Dempsey Cindy L.
Published: October 2023

At EHS Christ Hospital and Medical Center, an eight‐step process improvement model was developed that incorporates continuous quality improvement concepts for monitoring, evaluating, and improving patient care. Nursing home residents admitted with pneumonia were identified as the group having the most influence on mortality and costs associated with treatment of pneumonia at our hospital. A multidisciplinary team evaluated clinical resource use and patient care processes, and identified root causes of variations influencing treatment. Clinical guidelines were created and outcomes were defined, resulting in significant improvement in the clinical management of these patients. Average length of stay decreased from 8.6 days in 1992 to 7.6 days in 1993, with a charge reduction of $1830 per patient. The methodologic framework of a process improvement program combines epidemiologic, clinical, and quality improvement sciences. This mix is essential in improving patient care and quantifying outcomes.
The Risk of Sulfasalazine‐ and Mesalazine‐Associated Blood Disorders
Authors: Jick Hershel , Myers Marian Wald , Dean Alan D.
Published: October 2023

Sulfasalazine (SASP) has often been reported to cause serious blood disorders, particularly agranulocytosis; however, little quantitative information is available to estimate the risk or to identify possible modifiers of the risk. We used comprehensive clinical information recorded on office computers by selected general practitioners in Britain to conduct a follow‐up study of some 10,000 users of SASP and some 4000 users of mesalazine to estimate the risk of blood disorders associated with these drugs. Overall, the frequency of blood disorders attributable to SASP was 27/10,332 (2.6/1000 users). The risk for SASP users who were treated for arthritic disorders (6.1/1000 users) was some 10 times higher than that for users who were treated for inflammatory bowel disease (0.6/1000 users). There were no cases of blood disorders in users of mesalazine.
Toxicology and Management of Acute Drug Ingestions in Adults
Authors: Herrington Annie M. , Clifton G. Dennis
Published: October 2023

We reviewed the current literature on the toxicology and management of acute drug ingestions in adults after a MEDLINE search of English‐language journal articles. Information on toxicology was also acquired from relevant textbooks. Present statistics were gathered through information from the U.S. Department of Health and Human Services and the American Association of Poison Control Centers. All patients with acute drug ingestions should be treated with supportive care initially, and when stabilized, undergo active removal of the ingested substance, based on the diagnostic and prognostic assessment. Identification of the ingested substance may prove useful in some instances when specific therapy or antidotes are indicated.
Pharmacist‐Managed Aminoglycoside Therapy in Combination With a β‐Lactam Agent in the Treatment of Nosocomial Pneumonia in Critically Ill Patients
Authors: Wade William E. , McCall Charles Y.
Published: October 2023

We attempted to determine the outcome of treatment with aminoglycosides, dosed pharmacokinetically using traditional strategies, in combination with synergistic antibiotics in the management of nosocomial pneumonia in critically ill patients over a 1‐year period. Twenty‐three adults cared for in an intensive care unit received an aminoglycoside dosed by a pharmacist plus a β‐lactam antibiotic. Of these, 21 experienced clinical cure of the disease and 2 died of unrelated complications. No treatment failures were encountered. Therapy with aminoglycosides, dosed by traditional pharmacokinetic methods, in combination with synergistic antimicrobials, was effective in managing nosocomial pneumonia in this nontertiary care regional referral center.
A Computerized System to Improve Documentation and Reporting of Pharmacists' Clinical Interventions, Cost Savings, and Workload Activities
Authors: Zimmerman Christopher R. , Smolarek Richard T. , Stevenson James G.
Published: October 2023

A major factor in delivering patient care is documenting activities by pharmacists. This documentation is not only essential to sustain existing programs but necessary to justify future growth of resources. A computerized documentation system for clinical interventions and workload activities was developed in a 340‐bed university teaching hospital. With the expansion of its pharmaceutical care model, the department reworked its distribution process to allocate more pharmacist time for patient care. Manual documentation of these services, however, soon was identified as an obstacle. A software program was developed to alleviate the problems inherent with manual documentation. This “user‐friendly” program tracks clinical recommendations and interventions by pharmacists, and calculates cost savings/avoidance. It also facilitates monthly and annual reporting for department managers.
Pathophysiology of Schizophrenia and the Role of Newer Antipsychotics
Authors: Risch S. Craig
Published: October 2023

Schizophrenia is an illness with numerous neurobiologic features. It is hypothesized that patients may have a relative deficit of dopamine neurotransmission in the nigrostriatal and mesocortical tracts of the brain, as contrasted with an excess of dopamine neurotransmission in the mesolimbic area. The dopamine deficit may be related to the negative symptoms (blunted affect, anhedonia, asociality, inability to initiate and carry out complex tasks to completion) of schizophrenia, whereas the dopamine excess may be responsible for the positive symptoms (hallucinations, delusions, and thought disorder). Compared with healthy subjects, schizophrenic patients may also have increased levels of serotonin and decreased levels of norepinephrine in the brain. Conventional antipsychotic drugs nonselectively block dopamine D2 receptors throughout the central nervous system. This may help reduce positive symptoms, but has little or no effect on negative symptoms. Newer agents have more anatomically selective activity with respect to dopaminergic systems but are more complex with respect to their actions in other neurochemical systems, such as serotonin and norepinephrine, which presumably contributes to their apparent greater therapeutic efficacy.
Androgen UDP‐Glucuronyl Transferase Activity Is Found Primarily in Liver in the Rat
Authors: PIROG EDYTA C. , CLARK RICHARD V. , COLLINS DELWOOD C.
Published: October 2023

ABSTRACT: UDP‐glucuronyl transferase (UDPGT) activity was determined for androgens in tissue minces and microsomal fractions from the liver and extrahepatic tissues (kidney, skin, prostate, and preputial glands) of the male rat. Liver microsomes showed the highest UDPGT activity with each of the androgens tested (Vmax = 7, 3, and 10 nmol/minute/mg protein for testosterone, androsterone, and androstanediol, respectively). UDPGT activity (Vmax) for androstanediol in the liver was 102‐fold higher than in the kidney and 103‐fold higher than in the skin and prostate. UDPGT activity for androgens was not detected in microsomes from preputial glands. Furthermore, no body site distribution was found for androgen UDPGT activity in skin microsomes. The Michaelis‐Menten constant (Km) for UDPGT in liver microsomes was 20.4, 12.2, and 2.2 μ, respectively, for testosterone, androstanediol, and androsterone. Kidney microsomes showed a Km of 19.4 and 26.9 μ, respectively, for androstanediol and androsterone. The Km for testosterone was very high in the kidney (138 μ), suggesting that it was a poor substrate. In microsomes from the skin and prostate, the Km was very high (range 43–162 μ) for all three androgen substrates, suggesting that these androgens were not the preferred substrates for UDPGT in these tissues.

These results indicate that the liver was the main site of androgen UDPGT activity and the skin and prostate formed little, if any, androgen glucuronides. These results suggest that androstanediol glucuronide was formed primarily in the liver and may not be a reliable marker of peripheral androgen metabolism.