bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between homework time and academic and non‐academic performance in China: A preliminary test of the nonlinear hypothesis
Authors: Shao Yueyang , Liu Hongyun , Zhao Pingping , Liu Qimeng , Liu Jian
Published: October 2023

Inspired by complex system theory, this study adopts a multilevel piecewise regression model to examine the relationship between homework time and the development of students in different grades using a large‐scale testing database in China. The results indicate that the relationship between homework time and students’ performance is positive when homework time is less than the cut‐off values and becomes negative when homework time is greater than the cut‐off values. For different dependent variables, the cut‐off values of homework time differ but are all within a range (1–1.2 h for grade 4 and 1.7–2 h for grade 8). The reasons for the difference in cut‐off values among students in different grades are discussed.
Rosmarinic acid enhances CHO cell productivity and proliferation through activation of the unfolded protein response and the mTOR pathway
Authors: Mao Leran , Schneider James W. , Robinson Anne S.
Published: October 2023

Rosmarinic acid (RA) has gained attraction in bioprocessing as a media supplement to improve cellular proliferation and protein production. Here, we observe up to a two‐fold increase in antibody production with RA‐supplementation, and a concentration‐dependent effect of RA on cell proliferation for fed‐batch Chinese hamster ovary (CHO) cell cultures. Contrary to previously reported antioxidant activity, RA increased the reactive oxygen species (ROS) levels, stimulated endoplasmic reticulum (ER) stress, activated the unfolded protein response (UPR), and elicited DNA damage. Despite such stressful events, RA appeared to maintained cell health via mammalian target of rapamycin (mTOR) pathway activation; both mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) were stimulated in RA‐supplemented cultures. By reversing such mTOR pathway activity through either chemical inhibitor addition or siRNA knockdown of genes regulating the mTORC1 and mTORC2 complexes, antibody production, UPR signaling, and stress‐induced DNA damage were reduced. Further, the proliferative effect of RA appeared to be regulated selectively by mTORC2 activation and have reproduced this observation by using the mTORC2 stimulator SC‐79. Analogously, knockdown of mTORC2 strongly reduced X‐box binding protein 1 (XBP1) splicing, which would be expected to reduce antibody folding and secretion, sugging that reduced mTORC2 would correlate with reduced antibody levels. The crosstalk between mTOR activation and UPR upregulation may thus be related directly to the enhanced productivity. Our results show the importance of the mTOR and UPR pathways in increasing antibody productivity, and suggest that RA supplementation may obviate the need for labor‐intensive genetic engineering by directly activating pathways favorable to cell culture performance.
Hydrophobic ion pairing and microfluidic nanoprecipitation enable efficient nanoformulation of a small molecule indolamine 2, 3‐dioxygenase inhibitor immunotherapeutic
Authors: Badiee Parisa , Maritz Michelle F. , Dehghankelishadi Pouya , Dmochowska Nicole , Thierry Benjamin
Published: October 2023

Blockade of programmed cell death‐1 (PD‐1) is a transformative immunotherapy. However, only a fraction of patients benefit, and there is a critical need for broad‐spectrum checkpoint inhibition approaches that both enhance the recruitment of cytotoxic immune cells in cold tumors and target resistance pathways. Indoleamine 2, 3‐dioxygenase (IDO) small molecule inhibitors are promising but suboptimal tumor bioavailability and dose‐limiting toxicity have limited therapeutic benefits in clinical trials. This study reports on a nanoformulation of the IDO inhibitor navoximod within polymeric nanoparticles prepared using a high‐throughput microfluidic mixing device. Hydrophobic ion pairing addresses the challenging physicochemical properties of navoximod, yielding remarkably high loading (>10%). The nanoformulation efficiently inhibits IDO and, in synergy with PD‐1 antibodies improves the anti‐cancer cytotoxicity of T‐cells, in vitro and in vivo. This study provides new insight into the IDO and PD‐1 inhibitors synergy and validates hydrophobic ion pairing as a simple and clinically scalable formulation approach.
Improving the techno‐functionality of air‐classified pea flour fine fraction by enzymatic proteolysis, followed by Maillard‐induced conjugation with available carbohydrates in the flour
Authors: Mookerjee Abhiroop , Nickerson Michael , Tanaka Takuji
Published: October 2023

Background and Objectives

Air‐classified pea protein‐enriched flour (PPEF) was hydrolyzed with trypsin and papain and heat conjugated with the carbohydrate fraction of the flour via the Maillard reaction to form protein–carbohydrate conjugates. The surface and functional properties of the conjugates were assessed thereafter.

Findings

The surface charge of the conjugates (trypsin and papain conjugates) (−27.5 to −32.2 mV and −33.1 to −37.5 mV) was higher than that of PPEF (−24.2 ± 0.5 mV and −27.3 ± 1.1 mV) at pH 7 and 10. Low degrees of trypsin hydrolysis, followed by conjugation resulted in enhanced foam capacity (109.2% ± 2.0%), and heated trypsin controls had the highest foam stability (76.9%) at pH 4. The emulsion activity index of the hydrolyzed protein–carbohydrate conjugates (hydrolyzed proteins conjugated with starch) was higher at pH 4 (15.9–22.2 min) as compared to pH 7 (16.5–21.3 min). Trypsin conjugates showed the highest emulsion stability (ES) at pH 4 (96.4%–98%), whereas the ES at pH 7 and 10 was almost comparable. Both oil‐holding (OHC: 1.9–3.9 g/g) and water‐holding capacities (WHC: 1.7–2.4 g/g) were significantly improved.

Conclusions

Maillard conjugated proteins have enhanced functional properties at pH 4, 7, and 10 as compared to PPEF. Most of the conjugates show high functionality at pH 4. It was also observed that only heating the low‐cost, raw materials produced conjugates with enhanced functional properties.

Significance and Novelty

Enhanced functional properties at acidic pH are indicative of their use in beverage emulsions like fruit juices and processed drinks. High WHC and OHC show their potential use in the food industry as an alternative to animal proteins.
Is it possible to establish a calculable causal relationship between trauma and sporadic desmoid tumors?
Authors: Tzanis Dimitrios , Roland Christina Lynn
Published: October 2023

Traumatism and surgery are often found in the medical history of patients with sporadic desmoid tumors, as the recent article of the Mannheim Sarcoma Team has shown for 38.3% of patients. Still, it is not possible to establish a direct causality. Decoding the host environment can provide a more precise definition of any causal relationship.
A many‐objective optimization‐based local tensor factorization model for skin cancer detection
Authors: Zhao Haochen , Wen Jie , Yang Jinqian , Cai Xingjuan , Liu Chunxia
Published: October 2023

Exploring the associations between microRNAs (miRNAs) and diseases can identify potential disease features. Prediction of miRNA‐skin cancer associations has become an effective method for detecting skin cancer, as direct detection of skin cancer is challenging. However, traditional binary associations prediction methods overlook high‐order feature differences of miRNAs in different types of skin cancer. Although current tensor decomposition methods have addressed this, they assume a consistent composition standard of global tensor elements, ignoring differences in the composition standards of local sub‐tensors. This leads to poor prediction accuracy and comprehensiveness and fails to consider the credibility and diversity requirements of patients and doctors in practical applications. In this paper, we represent miRNA‐skin cancer associations as a tensor and employ tensor decomposition for tensor completion to achieve prediction purposes. First, we propose a credibility evaluation indicator and introduce four objective functions: accuracy, comprehensiveness, credibility, and diversity, to construct a many‐objective local tensor factorization model (MOLTF). Then, to avoid wrong individuals when solving this model with genetic algorithms, we propose a corrected single‐point crossover operator and a corrected multi‐point mutation operator. On the miRNA‐disease dataset HMDD v3.2, our algorithm improves accuracy by 14.5% compared to the recent baseline, demonstrating its effectiveness.
Studying Local Electrostatics by Terahertz Spectroscopy Using Amines as a Probe
Authors: Schulke Simon , Nolten Melinda , Schwaab Gerhard , Havenith Martina
Published: October 2023

In a previous study[1] we could show that a large amplitude mode of the zwitterion glycine can serve as a sensitive probe for protonation and allows to deduce local pKa values. Here we show that the underlying concept is more general: We present the results of a pH dependent measurement of Terahertz‐FTIR (THz‐FTIR) spectra of solvated amines, i. e. Diethylamine (DEA), Triethylamine (TEA), and Diisopropylamine (DiPA). We show that amines serve as a sensitive, label free probe for local protonation. Protonation of the amines yield intensity changes which can be quantified by precise THz spectroscopy (30 cm−1–450 cm−1). A detailed analysis allows us to correlate the titration spectra of solvated amines in the THz range with pKa values. This demonstrates the potential of THz spectroscopy to probe the charge state of biomolecules in water in a label free manner.
Recent Advances in Layered‐Double‐Hydroxide‐Based Separation Membranes
Authors: Li Biao , Xu Xiaozhi , Yang Zeya , Lu Jun , Han Jingbin
Published: October 2023

The use of two‐dimensional materials shows great promise for the development of next‐generation membrane materials, thanks to their atomic thinness and the ease with which precise nanochannels can be constructed. Among these materials, layered double hydroxides (LDHs) stand out as an important class, possessing many features that make them ideal for constructing high‐performance membranes. LDHs offer many advantages, such as their abundant and tunable interlayer anions, which enable the preparation of membranes with adjustable sub‐nanometer pore sizes. Additionally, their hydrophilicity and positive charge characteristics afford them unique benefits. LDHs have been found to be effective in gas separation, ion sieving, and nanofiltration. This review provides a summary of the latest progress in using LDHs for membrane separation. It begins by introducing the basic properties of LDHs, followed by the assembly strategy for LDH membranes. Furthermore, the review presents the research status of LDHs membranes in various fields in a systematic manner. Lastly, the paper highlights some challenges and future prospects for preparing and applying LDHs membranes.
Recent Advances in the Conversion of Methane to Syngas and Chemicals via Photocatalysis
Authors: Li Ruitao , Zheng Yihan , Gong Kun , He Zhanjun , Dai Yuanyuan , Niu Qiang , Lin Tiejun , Zhong Liangshu
Published: October 2023

As a primary constituent of natural gas and shale gas, direct conversion of methane has attracted significant attention due to its potential to reduce energy consumption and CO2 emissions. Compared with thermal catalysis, photocatalysis has the capacity to transcend thermodynamic constraint and enable the conversion of sustainable solar energy into chemical energy under mild reaction condition, which contributes to optimize the utilization of methane. In this review, we undertake a comparative analysis of various strategies for photocatalytic methane conversion to syngas and chemicals, including photocatalytic reforming of methane, photocatalytic partial oxidation of methane and photocatalytic coupling of methane. The distinct reaction systems with corresponding catalysts and underlying mechanisms are expounded in detail to foster a profound comprehension of solar‐driven methane conversion. Finally, the challenges and prospectives in photocatalytic methane conversion are discussed.
Ionic Liquid Boosting the Electrochemical Stability of a Poly(1,3‐dioxolane) Gel Electrolyte for High‐voltage Solid‐State Lithium Batteries
Authors: Chen Tianhua , Liu Jiaxin , Losic Dusan , Wang Jian , Zhang Haitao
Published: October 2023

Poor interfacial contact between solid‐state electrolytes and electrodes limits high‐voltage performance of solid‐state lithium batteries. A new gel electrolyte is proposed via in‐situ polymerization, incorporating fluoroethylene carbonate (FEC) solvent and ionic liquid1‐butyl‐1‐methylpiperidinium bis(trifluoromethylsulfonyl)imide (PP14TFSI). This combination synergistically enhances Li ion transport, achieving a transfer number of 0.58 and improved electrochemical performance. FEC protects the Al current collectors from LiPF6 corrosion and promotes a protective interfacial layer formation. PP14TFSI improves interfacial contact and provides stable components. An interface layer of fluorine and nitrogen composites forms, preventing side reactions. LiCoO2||PPE||Li cell exhibits robust cycling stability at 4.45 V, retaining ~80 % capacity after 200 cycles at room temperature with 0.2 C and 1 C rates, showing increased coulombic efficiency. NCM811||PPE||Li cell also displays exceptional cycling. In‐situ polymerization and FEC‐ionic liquid coordination enable high‐voltage solid‐state lithium metal batteries for practical use.
Investigating tritrophic interactions using bioenergetic demographic models
Authors: Passoni Gioele , Coulson Tim , Cagnacci Francesca , Hudson Peter , Stahler Daniel R. , Smith Douglas W. , Lachish Shelly
Published: October 2023

A central debate in ecology has been the long‐running discussion on the role of apex predators in affecting the abundance and dynamics of their prey. In terrestrial systems, research has primarily relied on correlational approaches, due to the challenge of implementing robust experiments with replication and appropriate controls. A consequence of this is that we largely suffer from a lack of mechanistic understanding of the population dynamics of interacting species, which can be surprisingly complex. Mechanistic models offer an opportunity to examine the causes and consequences of some of this complexity. We present a bioenergetic mechanistic model of a tritrophic system where the primary vegetation resource follows a seasonal growth function, and the herbivore and carnivore species are modeled using two integral projection models (IPMs) with body mass as the phenotypic trait. Within each IPM, the demographic functions are structured according to bioenergetic principles, describing how animals acquire and transform resources into body mass, energy reserves, and breeding potential. We parameterize this model to reproduce the population dynamics of grass, elk, and wolves in northern Yellowstone National Park (USA) and investigate the impact of wolf reintroduction on the system. Our model generated predictions that closely matched the observed population sizes of elk and wolf in Yellowstone prior to and following wolf reintroduction. The introduction of wolves into our basal grass–elk bioenergetic model resulted in a population of 99 wolves and a reduction in elk numbers by 61% (from 14,948 to 5823) at equilibrium. In turn, vegetation biomass increased by approximately 25% in the growing season and more than threefold in the nongrowing season. The addition of wolves to the model caused the elk population to switch from being food‐limited to being predator‐limited and had a stabilizing effect on elk numbers across different years. Wolf predation also led to a shift in the phenotypic composition of the elk population via a small increase in elk average body mass. Our model represents a novel approach to the study of predator–prey interactions, and demonstrates that explicitly considering and linking bioenergetics, population demography and body mass phenotypes can provide novel insights into the mechanisms behind complex ecosystem processes.
Belowground niche partitioning is maintained under extreme drought
Authors: Weides Sophie E. , Hájek Tomáš , Liancourt Pierre , Herberich Maximiliane M. , Kramp Rosa E. , Tomiolo Sara , Pacheco‐Riaño L. Camila , Tielbörger Katja , Májeková Maria
Published: October 2023

Belowground niche partitioning presents a key mechanism for maintaining species coexistence and diversity. Its importance is currently reinforced by climate change that alters soil hydrological conditions. However, experimental tests examining the magnitude of its change under climate change are scarce. We combined measurements of oxygen stable isotopes to infer plant water‐uptake depths and extreme drought manipulation in grasslands. Belowground niche partitioning was evidenced by different water‐uptake depths of co‐occurring species under ambient and extreme drought conditions despite an increased overlap among species due to a shift to shallower soil layers under drought. A co‐occurrence of contrasting strategies related to the change of species water‐uptake depth distribution was likely to be key for species to maintain some extent of belowground niche partitioning and could contribute to stabilizing coexistence under drought. Our results suggest that belowground niche partitioning could mitigate negative effects on diversity imposed by extreme drought under future climate.
High frequency environmental DNA metabarcoding provides rapid and effective monitoring of fish community dynamics
Authors: Hallam Jane , Clare Elizabeth L. , Jones John Iwan , Day Julia J.
Published: October 2023

Long‐term monitoring is critical to measure the response of biodiversity patterns and processes to human‐mediated environmental pressures. This is particularly pertinent in freshwaters, where recent estimates indicated a third of all fish species are threatened with extinction, making ongoing biomonitoring essential for conservation management. High frequency annual monitoring is critical for identifying temporal changes in fish community composition; however, traditional survey methods are typically less practical over such timeframes. While environmental (e)DNA measurement represents a potentially powerful tool for monitoring temporal community dynamics, studies are lacking. To address this deficit, we generated a high frequency time‐series dataset of entire fish communities using eDNA metabarcoding, to directly assess the repeatability and sensitivity of this method for detecting annual population trends. We targeted two differing environments (freshwater vs. intertidal) within the Thames catchment, UK, where detailed historical records from traditional monitoring were available for comparison. To test how robust eDNA data is for inferring the known community, we applied a hierarchical, nested design encompassing short and longer‐term variation in eDNA data. Our analyses showed that irrespective of environment, eDNA metabarcoding represented known seasonal shifts in fish communities, where increased relative read abundance of eDNA coincided with known migratory and spawning events, including those of the critically endangered native species Anguilla anguilla (European eel). eDNA species detections across a single year included over 75% of species recorded in a ca. 30‐year historical dataset, highlighting the power of eDNA for species detection. Our findings provide greater insight into the utility of eDNA metabarcoding for recovering temporal trends in fish communities from dynamic freshwater systems and insight into the potential best sampling strategy for future eDNA surveys.
Hydralazine combined with conventional therapy improved outcomes in severe systolic dysfunction and mitral regurgitation
Authors: Hsiao Shih‐Hung , Hsiao Chao‐Sheng , Shiau Jau‐Wen , Chiou Kuan‐Rau
Published: October 2023

Aims

Patients with heart failure (HF) and reduced left ventricular ejection fraction (LVEF) accompanied by significant mitral regurgitation (MR) had poor outcome. Several vasodilator trials showed neutral results. We aimed to investigate the effect of early up‐titration of hydralazine combined with conventional treatment in acute HF with severe systolic dysfunction and significant MR.

Methods and results

The study was open‐labelled, one‐to‐one ratio randomized designed. Consecutively hospitalized patients with decompensated HF symptoms, LVEF < 35%, and MR more than moderate severity were enrolled after exclusion. All participants with inadequate preload should have intake promotion with/without fluid supply. Patients receiving evidence‐based medications (EBMs) as conventional treatment served as the control. Hydralazine + conventional treatment group received up‐titration of hydralazine at Days 1–5 of the index admission combined with EBMs and throughout the course of follow‐up. The endpoints included cardiovascular (CV) death and HF rehospitalization. Totally, 408 patients were enrolled (203 in conventional treatment and 205 in hydralazine + conventional treatment). The mean follow‐up period was 3.5 years. The mean dose of hydralazine was 191 mg at index admission and 264 mg at study end in hydralazine + conventional treatment group. Both groups did not significantly differ in prescription rates and dosages of EBMs (all P > 0.05) at study end. Side effects did not differ between the two groups. Finally, 51% (104 out of 203 cases) reached endpoints in conventional group and 34.6% (71 out of 205 cases) in hydralazine + conventional treatment group, which had a significant reduction in CV events (hazard ratio 0.613, 95% confidence interval 0.427–0.877, P < 0.001). In‐hospital death during the index admission was significantly higher in conventional group (5.4% vs. 0.5%, respectively; P = 0.001).

Conclusions

When administered without inadequate preload, combining early up‐titration of hydralazine with EBMs improves outcome in patients with severe systolic dysfunction and significant MR, and it is safe and well tolerated.
Applicability of Redirecting Artemisinins for New Targets
Authors: Golenser Jacob , Hunt Nicholas H. , Birman Ida , Jaffe Charles L. , Zech Johanna , Mäder Karsten , Gold Daniel
Published: October 2023

Employing new therapeutic indications for drugs that are already approved for human use has obvious advantages, including reduced costs and timelines, because some routine steps of drug development and regulation are not required. This work concentrates on the redirection of artemisinins (ARTS) that already are approved for clinical use, or investigated, for malaria treatment. Several mechanisms of action are suggested for ARTS, among which only a few have been successfully examined in vivo, mainly the induction of oxidant stress and anti‐inflammatory effects. Despite these seemingly contradictory effects, ARTS are proposed for repurposing in treatment of inflammatory disorders and diverse types of diseases caused by viral, bacterial, fungal, and parasitic infections. When pathogens are treated the expected outcome is diminution of the causative agents and/or their inflammatory damage. In general, repurposing ARTS is successful in only a very few cases, specifically when a valid mechanism can be targeted using an additional therapeutic agent and appropriate drug delivery. Investigation of repurposing should include optimization of drug combinations followed by examination in relevant cell lines, organoids, and animal models, before moving to clinical trials.
Eudiaptomus hadzici (Brehm) (Crustacea: Copepoda) from the Dinarid Karstic Area
Authors: Bukvić Ivančica , Kerovec Mladen , Mihaljevkič Zlatko
Published: October 2023

During biological research in 1995/96 of Lake Visovac in karstic Dinarid area, a large number of calanoid and cyclopoid copepods were obtained from plankton. Among these materials, the uncommon high mountain species Eudiaptomus hadzici (Brehm, 1939) was recognized. The discovery of this species in a karstic Mediterranean lake at an altitude of 32 m is noteworthy and of some ecological value. It has never before been collected in Dinarid area, having been recorded only in high mountain glacial lakes in the south of the Balkan peninsula (Macedonia and Albania) and in periodical karstic lakes in the montane region (Slovenia). The distribution of this species is still little known and it is most probable that its geographical range could be enlarged by further investigations. In this work a short morphological description of the species found in Dinarid karst is given and also some notes on its ecology.
Management Impacts on Stand Structure of Lakeshore Phragmites Reeds
Authors: Ostendorp Wolfgang
Published: October 2023

Many lakeside Phragmites australis reeds are frequently harvested or burnt in winter for several purposes like extraction of raw material, natural preservation or facilitation of professional fishing or fish breeding. The question is, whether these practices support a sustainable development of the reeds. Data from a long term monitoring program at Lake Constance (Germany) demonstrate that culm morphology, stand structure and aboveground peak biomass are strongly influenced by the treatment. Winter harvested and burnt reeds exhibited higher culm densities (+76% of the untreated controls), and a higher peak biomass (+13%). The mean culm height was reduced by −13%. The percentage of insect infested shoots was 8.8% of the total shoot population, compared with 20.1% of the untreated controls. Consecutive harvesting treatments intensified these effects. In the first two years after the treatment had stopped the reed stands showed an ‘overshoot’ biomass production, and a strong trend towards the features of the untreated controls. The possible mechanisms (mechanical damage, frost kill of the growth tips and breaking of the apical dominance) are discussed. It is concluded that winter harvesting and burning treatments make the reeds more susceptible against some environmental hazards, and should therefore applied with precaution on the basis of a close examination of risks and benefits.
Competition between the CyanobacteriumLimnothrix redekeiand Some Spring Species of Diatoms under P‐Limitation
Authors: Nicklisch Andreas
Published: October 2023

The nutrient saturated growth and the competition betweenLimnothrix redekeiand some spring diatoms for phosphate were studied in semi‐continuous cultures at 10°C with a 6/18 h light/dark cycle and at 15 °C with a 12/12 light/dark cycle. Under these conditions in unialgal cultures, the maximum specific growth rate ofLimnothrix redekeiwas two to three time lower than that of the diatoms. However,Limnothrix redekeiwas the superior competitor for phosphate under both conditions in mixed cultures. The diatoms in mixed cultures from each species withLimnothrix redekeiwere competitively displaced but at a different rate. This allowed the diatoms to be ranked in terms of their competitive ability for phosphate at 10°C as follows:Synedra acus > Asterionella formosa > Stephanodiscus minutulus > Nitzschia acicularis > Cyclotella meneghiniana > Stephanodiscus neoastrea > Stephanodiscus hantzschii.The competitive ability ofLimnothrix redekeiat 15 °C was increased and the rank order of diatoms slightly changed. The hypothesis that cyanobacteria are promoted by phosphate because they are inferior competitors for phosphate is incorrect forLimnothrix redekei.
Forms and Mobility of Sediment Phosphorus in Shallow Eutrophic Lake Võrtsjärv (Estonia)
Authors: Nõges Peeter , Kisand Anu
Published: October 2023

The surficial sediment (0–10 cm) of shallow eutrophic Lake Võrtsjärv (Estonia) was characterized by an acid insoluble residue of 50% dry weight and low nutrient, Fe and Mn content. Among phosphorus (P) fractions (Hieltjes and Lijklema, 1980), NaOH‐NRP amounted on an average to 50%, HCl‐RP to 30%, NaOH‐RP to 16%, and NH4Cl‐RP to 4% of their sum. Seasonal changes in sediment P content were inconsistent with mass balance calculations and could be attributed to sediment redistribution caused by decreasing water level. High Fe/P ratio (26–30) and the aeration of surficial sediment by frequent resuspension kept phosphate adsorbed. Low pore‐water SRP (commonly <10 μg l−1) usually prevented phosphate release from surficial sediment. However, a storm in September 1996 (max. wind speed 16 m s−1) which coincided with the extremely low water level in the lake (mean depth 1.44 m), denuded deeper anoxic sediment layers and caused a SRP release of 193 mg P m−2 d−1.
Woody Debris Accumulations — Important Ecological Components in a Low Order Forest Stream (Weidlingbach, Lower Austria)
Authors: Weigelhofer G. , Waringer J. A.
Published: October 2023

From May 1996 to February 1998, the density of debris dams was surveyed in monthly intervals along a 750‐m‐long, third order section of the Weidlingbach, a fourth order sandstone brook in the Wienerwald. The mean density over the whole study period was one woody debris accumulation per 35 m stream length. The longevity of these structures ranged from one month to over one year, depending on the hydrology of the stream. More than 50% of the accumulations outlasted moderate floods (0.3–0.4 m3 s−1); of these, 52% were tightly fixed to the bank vegetation. However, only 12% of the destroyed dams were anchored in any way. In addition, two dams were sampled for macroinvertebrate colonisation every other month from June 1996 to June 1997. Dry weights of the leaf and wood fraction were determined and macroinvertebrates identified. Within dams, organismic densities were lowest in temporarily dry levels at the top of debris accumulations (mean density =171 specimens dm−3) and highest in permanently submerged levels near the water surface as well as in patches with high leaf litter concentrations (mean density = 1240 specimens dm−3). Within the topmost 5 cm sediment layer mean macroinvertebrate density was 67.7 specimens dm−3. Within debris dams, taxa composition was not significantly different between the lowermost level 1 and the sediment surface and among levels within dams; however, significant differences existed between the topmost level 4 and all other dam levels. In level 4, we observed significantly more terrestrial Diptera taxa and Coleoptera and significantly fewer Plecoptera and Gammaridae.
Pigment Content of Selected Planktonic Algae in Response to Simulated Natural Light Fluctuations and a Short Photoperiod
Authors: Nicklisch Andreas , Woitke Peter
Published: October 2023

The lipophilic photosynthetic pigments inLimnothrix redekei, Planktothrix agardhii(cyanobacteria),Stephanodiscus minutulus, Synedra acus(diatoms),Scenedesmus acuminatus, andScenedesmus armatus(chlorophycean) all isolated from an eutrophic lake were quantitatively determined by HPLC. The algae were grown semi‐continuously under nutrient sufficient conditions at 20°C at a 12/12 h light/dark cycle with constant irradiance or with simulated natural light fluctuations as well as at a 6/18 h light/dark cycle with constant irradiance, all at the same daily light exposure.

The zeaxanthin and the myxoxanthophyll contents of cyanobacteria were not influenced by fluctuating light, a short photoperiod or a different sampling time. The chlorophyllb/aratio, the lutein/chlorophyllaratio, and the neoxanthin content of chlorophycean as well as the chlorophyllc/aand the fucoxanthin/chlorophyllaratio of diatoms were only slightly influenced by these factors. Therefore in some cases marker pigment contents and in other cases marker pigment/chlorophyllaratios may be more useful for quantifying the relative importance of different taxonomic groups in natural phytoplankton. Simulated natural light fluctuations or the length of the photoperiod only slightly influenced the pigment content or the marker pigment/chlorophyllaratio.
Can Insulin Therapy Delay or Prevent Insulin‐Dependent Diabetes Mellitus?
Authors: Kakka Reena , Koda‐Kimble Mary Anne
Published: October 2023

Although the precise events preceding insulin‐dependent diabetes mellitus (IDDM, type 1 diabetes) have not yet been elucidated, it is known that IDDM results from a slow, progressive, immune process directed against pancreatic islet β cells. Disrupting this autoimmune process has been the focus of research aimed at preventing or slowing the disease progression. Technologic advances in predicting the onset and likelihood of developing IDDM have made it possible to study the effects of early immune intervention. The National Institutes of Health recently launched a large‐scale, multicenter trial to evaluate the effectiveness of insulin as preventive therapy. Although many different immunosuppressive and immunomodulating agents have been investigated, the use of insulin as a prophylactic agent is a fairly recent concept. Several methods have been used to halt the autoimmune destruction of the pancreas, with animal and human studies serving as the basis for insulin in preventing IDDM.
Comparative Pharmacokinetics of Oral Ceftibuten, Cefixime, Cefaclor, and Cefuroxime Axetil in Healthy Volunteers
Authors: Nix David E. , Symonds William T. , Hyatt Judith M. , Wilton John H. , Teal Marilyn A. , Reidenberg Pascale , Affrime Melton B.
Published: October 2023

Study Objective. To compare the pharmacokinetics of ceftibuten, cefixime, cefuroxime axetil, and cefaclor after oral administration.

Design. Randomized, four‐period, crossover study.

Setting. Hospital‐based clinical research center.

Subjects. Healthy adult men and women volunteers.

Interventions. Single 400‐mg doses of cefixime and ceftibuten, and 500‐mg doses of cefuroxime axetil and cefaclor.

Measurements and Main Results. Serum concentrations were determined by high‐performance liquid chromatography methods. The mean oral clearances of cefixime, cefuroxime axetil, and cefaclor were similar, ranging from 20.4–27.0 L/hour; clearance of ceftibuten was approximately 4‐fold less, 5.45 L/hour. The serum half‐lives of ceftibuten (2.35 hrs) and cefixime (2.38 hrs) were prolonged compared with those of cefuroxime axetil (1.30 hrs) and cefaclor (0.693 hr). These agents also differed in terms of time to maximum concentration, time to peak plasma level, area under the curve, and apparent volume of distribution, the last reflecting differences in bioavailability.

Conclusion. Ceftibuten had a relatively high time to maximum concentration and long half‐life, resulting in a 3.5‐fold higher area under the curve than cefixime, cefuroxime axetil, and cefaclor. These pharmacokinetic data can be used as a basis to compare the four oral cephalosporins; however, comparative susceptibility data must also be considered.
Clinical and Economic Considerations of Vaccination Against Varicella
Authors: Strassels Scott A. , Sullivan Sean D.
Published: October 2023

We evaluated the medical and economic literature pertaining to varicella vaccine in healthy children in an effort to provide perspective for both clinicians and those responsible for making payment policies. Chickenpox is relatively mild in most immunocompetent children; however, disease‐related direct and indirect medical costs have been estimated at approximately $400 million/year. A vaccine effective in preventing the disease is now available in the United States and may offset some of these expected costs. Universal vaccination for patients older than 12 months of age without history of varicella infection or other contraindication is recommended by the American Academy of Pediatrics. It is estimated that it would save $0.90/dollar spent and $5.40/dollar spent from payers' and society's perspectives, respectively. Thus varicella vaccination is cost‐beneficial only when considered from a societal perspective.
Communication Between Pharmacists and Patients: The Role of Place of Residence in Determining the Expectations of Older Adults
Authors: Ranelli Paul L. , Coward Raymond T.
Published: October 2023

The relationship between the place of residence of elderly patients and their expectations about the content and style of their communication with pharmacists was studied. Using stratified random sampling of households, telephone interviews were completed in Spring 1994 with 200 rural and 200 urban persons age 65 or older currently taking a prescribed drug that they picked up at a pharmacy. Respondents were asked about their sociodemographic characteristics, health, and experiences with prescription drugs. Factor analysis of items measuring the elders' expectations yielded one factor with nine items. Multivariate analysis was used to examine the effect of residence while controlling for other variables. Subjects currently took 3.2 ± 2.2 drugs (mean ± SD). Fifty‐two percent of rural elders used independent pharmacies, and 83% of urban elders used chain pharmacies. On six of the nine items in the expectation scale, rural elders held significantly different (higher) expectations for their pharmacists compared with urban elders. The most fully specified model contained five variables significantly associated with higher expectations: elders who took fewer drugs and who had a stroke, angina, osteoporosis, and no coronary heart disease. Although place of residence was a significant predictor of elders' expectations in the first three models, it was not when drug experiences were added in. Overall, older people in different places of residence have dissimilar personal and drug characteristics, and pharmacists practicing in different community contexts can anticipate encountering different patient expectations.
Suspected Acute Interstitial Nephritis Induced by Piperacillin‐Tazobactam
Authors: Pill Michael W. , O'Neill Christine V. , Chapman Michelle M. , Singh Ajay K.
Published: October 2023

A 51‐year‐old woman developed an acute onset of renal dysfunction accompanied by rash, lumbar pain, arthralgias, fever, eosinophiluria, and an elevated serum creatinine after 6 days of intravenous piperacillin‐tazobactam therapy. On discontinuing piperacillin‐tazobactam and after a 21‐day course of prednisone, the patient's constitutional symptoms dissipated and her renal function returned to baseline. Acute interstitial nephritis has been reported as an adverse effect of many drugs, including antibiotics, but not, to our knowledge, after piperacillin‐tazobactam. The time course of events suggested that piperacillin‐tazobactam was the cause of acute interstitial nephritis in this patient.
Warfarin‐Fluoxetine and Diazepam‐Fluoxetine Interaction
Authors: Dent Larry A. , Orrock Marv W.
Published: October 2023

Fluoxetine and its metabolite norfluoxetine are eliminated by oxidative metabolism via the CYP450 system and may inhibit the oxidative metabolism of other drugs to various degrees. A fluoxetine‐warfarin interaction has been postulated, but is not well documented in the literature. The elimination of diazepam may also be inhibited by fluoxetine. An elderly man was prescribed these three drugs in combination and experienced such an interaction. He developed an elevated international normalized ratio (INR) and died from a cerebral hemorrhage. He also manifested drug delirium secondary to inhibited diazepam metabolism. In elderly patients receiving fluoxetine, lorazepam or oxazepam would be safer alternatives to diazepam since they are conjugated in the liver. Patients stabilized on warfarin should be monitored closely for changes in INR if fluoxetine is added or deleted.
Pharmacology of the Taxanes
Authors: Dorr Robert T.
Published: October 2023

The taxanes paclitaxel and docetaxel are structurally similar, but they have different pharmacologic characteristics. Both bind to the β‐subunit of tubulin and affect microtubule polymerization. The cell cycle phases affected by the drugs are distinctly different; paclitaxel inhibits cell cycle traverse at the G2‐M phase junction, and docetaxel produces maximum cell killing against cells in S phase. The drugs both undergo hepatic metabolism; however, the specific cytochrome P‐450 (CYP) enzymes responsible for hydroxylation are CYP 2C8 for paclitaxel and CYP 3A4 for docetaxel. The cytotoxic effects of the taxanes are schedule dependent. For both drugs, longer durations of exposure increase cytotoxicity. Studies are being conducted to determine if prolonged exposure in cancer cell lines increases response rates in patients with sensitive tumors. The distinct mechanistic and metabolic differences between paclitaxel and docetaxel may influence clinical efficacy and safety in patients with cancer.
Clinical Overview of the Taxanes
Authors: Goldspiel Barry R.
Published: October 2023

Paclitaxel and docetaxel are taxane antineoplastic agents with broad antitumor activity. Since being introduced, they have become increasingly important in the treatment of a number of major solid tumors. Paclitaxel plus a platinum analog is now considered first‐line therapy for advanced ovarian cancer, and both paclitaxel and docetaxel have significant activity as single agents in recurrent ovarian cancer. Docetaxel may be useful in some of these women with ovarian cancer who fail or progress after paclitaxel‐containing treatments. Both drugs have significant response rates in the treatment of breast cancer and are options for patients with advanced disease, including anthracycline‐refractory disease. Administration of taxanes in new combination regimens and as adjuvant therapy for breast cancer is under investigation; for example, the combination of paclitaxel and doxorubicin is highly active, and comparative studies of taxanes and anthracyclines should help clarify optimal treatment regimens in breast cancer. Both drugs have significant activity alone in the treatment of advanced non‐small cell lung cancer (NSCLC) and head and neck cancers. For the former, paclitaxel‐cisplatin is now standard treatment in cooperative group combination therapy trials. As a result of its radiosensitizing properties, paclitaxel is undergoing extensive evaluation as combined modality treatment for advanced NSCLC and head and neck cancer. Both taxanes will probably be useful in combination regimens in head and neck cancer. Research is continuing to define further their roles and relative usefulness in other malignancies.
Pharmaceutical Properties of Paclitaxel and Their Effects on Preparation and Administration
Authors: Trissel Lawrence A.
Published: October 2023

Paclitaxel is a mainstay in the treatment of ovarian and breast cancers, and its use in other malignancies is being explored. Although it has great clinical utility, the drug and its formulation components pose a number of challenges to pharmacists and nurses. Paclitaxel is insoluble in water and is formulated in an equal parts mixture of ethanol and Cremophor EL, which disperses the drug in an aqueous medium. At concentrations of 0.3‐1.2 mg/ml, paclitaxel is stable for at least 2 days. Additional research identified precipitation as the major limitation to long‐term stability and supports the use of an inline filter for all infusions. The formulation vehicle also leaches the plasticizer DEHP from polyvinyl (PVC)‐containing solution bags and administration sets. This effect is dependent on the concentration of surfactant, the amount of accessible DEHP, and many other factors. Health care practitioners must educate themselves regarding appropriate non‐PVC containers and administration sets for safe and convenient delivery of paclitaxel. The compatibility of this and other drugs in solution is under investigation; currently, amphotericin B, chlorpromazine, hydroxyzine, methylprednisolone sodium succinate, and mitoxantrone have been determined to be physically incompatible with paclitaxel infusions.
Quetiapine, an Atypical Antipsychotic
Authors: Goren Jessica L. , Levin Gary M.
Published: October 2023

The discovery of antipsychotic agents in the 1950s revolutionized the treatment of schizophrenia. A large body of evidence supports the dopamine D2 receptor antagonist's efficacy in the treatment of psychotic symptoms. However, the advent of newer agents seems to point to a more complex interaction of neurotransmission in the pathophysiology of schizophrenia. In fact, a defining characteristic of atypical agents is a higher ratio of serotonin (5HT2) receptor blockade to D2 receptor blockade. Clozapine was the first atypical agent to be introduced; it was followed by risperidone, olanzapine, and now quetiapine, which is a dibenzothiazepine derivative structurally related to clozapine and olanzapine.
Repaglinide, a Novel, Short‐Acting Hypoglycemic Agent for Type 2 Diabetes Mellitus
Authors: Guay David R. P.
Published: October 2023

Repaglinide is a new, short‐acting, insulin‐releasing agent recently approved for the monotherapy of type 2 diabetes mellitus, and in combination with metformin in patients failing repaglinide or metformin monotherapy. Repaglinide appears to trigger insulin release by regulating adenosine triphosphate‐sensitive potassium channels on the surface of pancreatic β cells, which in turn affect calcium influx, the principal mediator of insulin release. Repaglinide mainly affects postprandial plasma glucose concentrations. It reduces glycosylated hemoglobin concentrations by 1–2% U. The agent's short duration of action may lessen the risk of long‐lasting hypoglycemia and of down‐regulation of β cell sensitivity (the latter promoting secondary drug failure), although data are sparse in this regard. Its major adverse effect is hypoglycemia. Its role in the therapy of type 2 diabetes is unclear at present, vis‐a‐vis its use instead of or in combination with other antidiabetic agents other than metformin. The need for multiple daily doses, based on its brief duration of action, may be a barrier to compliance.
Alteration in Indinavir Clearance During Interleukin‐2 Infusions in Patients Infected with the Human Immunodeficiency Virus
Authors: Piscitelli Stephen C. , Vogel Susan , Figg William D. , Raje Sangeeta , Forrest Alan , Metcalf Julia A. , Baseler Michael , Falloon Judith
Published: October 2023

Study Objective. To evaluate the effect of interleukin‐2 (IL‐2) infusions on the pharmacokinetics of indinavir in patients infected with the human immunodeficiency virus.

Design. Observational, noncontrolled trial and prospective, open‐label, nonrandomized, pharmacokinetic study.

Setting. Government research hospital.

Patients. Seventeen patients receiving indinavir 800 mg every 8 hours and a 5‐day continuous infusion of recombinant IL‐2.

Interventions. Observational study: trough indinavir concentrations were measured on day 1 and day 5 of IL‐2 as part of a clinical trial. Prospective study: serial plasma samples were collected on days 1 and 5 of IL‐2 to determine indinavir concentrations. Samples were also collected over the study period to determine IL‐6 concentrations. The data were fit by a one‐compartment model that allowed clearance to change based on IL‐6 production and by standard noncompartmental equations.

Measurements and Main Results. The area under the curve of indinavir increased in eight of nine patients by a mean of 88% (range −29–215%) between days 1 and 5 of IL‐2 infusion. Over this period, IL‐6 concentrations also increased in all patients and indinavir clearance significantly decreased. Observational data in eight patients from the clinical trial showed significantly increased indinavir trough concentrations from 264 ± 493 to 670 ± 677 ng/ml in the presence of IL‐2.

Conclusion. Indinavir concentrations were altered during IL‐2 infusions, possibly by induction of IL‐6. Investigation into the effects of other proinflammatory cytokines is warranted.