bluuebunny/crossref_metadata_2025 huggingface dataset:
Precision medicine analysis of heterogeneity in individual‐level treatment response to amyloid beta removal in early Alzheimer's disease
Authors: Pang Menglan , Gabelle Audrey , Saha‐Chaudhuri Paramita , Huijbers Willem , Gafson Arie , Matthews Paul M. , Tian Lu , Rubino Ivana , Hughes Richard , de Moor Carl , Belachew Shibeshih , Shen Changyu
Published: October 2023

INTRODUCTION

Alzheimer's disease (AD) is a neurological disorder with variability in pathology and clinical progression. AD patients may differ in individual‐level benefit from amyloid beta removal therapy.

METHODS

Random forest models were applied to the EMERGE trial to create an individual‐level treatment response (ITR) score which represents individual‐level benefit of high‐dose aducanumab relative to the placebo. This ITR score was used to test the existence of heterogeneity in treatment effect (HTE).

RESULTS

We found statistical evidence of HTE in the Clinical Dementia Rating–Sum of Boxes (CDR‐SB;P =  0.034). The observed CDR‐SB benefit was 0.79 points greater in the group with the top 25% of ITR score compared to the remaining 75% (P = 0.020). Of note, the highest treatment responders had lower hippocampal volume, higher plasma phosphorylated tau 181 and a shorter duration of clinical AD at baseline.

DISCUSSION

This ITR analysis provides a proof of concept for precision medicine in future AD research and drug development.

Highlights

Emerging trials have shown a population‐level benefit from amyloid beta (Aβ) removal in slowing cognitive decline in early Alzheimer's disease (AD).

This work demonstrates significant heterogeneity of individual‐level treatment effect of aducanumab in early AD.

The greatest clinical responders to Aβ removal therapy have a pattern of more severe neurodegenerative process.
Implementation of a Colorectal Surgical Site Infection Prevention Bundle and Checklist: A Quality Improvement Project
Authors: White Carrie , Kurtz Sarah , Lusk Leandra , Wilson Brigitte , Britton Vickie , Hayden Karen , Hunt Sarah , Hyland Jennifer , Kittrell William , Maddox Jason , Tanner Ashley , Tucker Valerie
Published: October 2023

After noting an elevated surgical site infection rate in 2019 associated with colorectal surgeries, leaders at two Central Virginia health system hospitals convened an interdisciplinary team to audit current practices and research infection prevention strategies. After identifying a lack of standardization in care processes for colorectal surgery patients and reviewing the literature on colorectal bundles, the team created a bundle focusing on the use of antibiotics, chlorhexidine gluconate wipes or baths, separate closing instrument trays, nasal decolonization, bowel preparation, and maintaining patient normothermia. After synthesis and stakeholder input, the team implemented the colorectal bundle along with a checklist for all users to complete to ensure compliance and standardization of practice and for auditing purposes. Implementation results were positive: the total number of colorectal infections decreased from nine in 2020 to three in 2021. Education was critical to securing staff member engagement for successful implementation of and compliance with the bundle.
Clinical Issues — November 2023
Authors: Seeman Kristyn
Published: October 2023

THIS MONTH

Securing sterile drapes with skin staples

Key words: sterile drapes, manufacturer's instructions for use, skin stapler, skin integrity, puncture wound.

Sterility of rubber stoppers on medication vials

Key words: rubber stopper, medication vial, alcohol swab, dust cover, contamination.

Social media use in the OR

Key words: social media, distractions, personal electronic device, Health Insurance Portability and Accountability Act (HIPAA), liability.

Staffing for local‐only anesthesia procedures

Key words: staffing, RN circulator, patient acuity, monitoring, local anesthetic systemic toxicity (LAST).
Exploring the Versatility of the Amidation of Aryl Acid Fluorides using the Germylamines R3GeNMe2
Authors: Fortney Vanessa A. , Murphy Julia K. , Stancil Thad R. , Gembicky Milan , Rheingold Arnold L. , Weinert Charles S.
Published: October 2023

The formation of amide bonds is an important process since this linkage is an essential component in proteins, pharmaceuticals, and other medicinally and biologically significant molecules. Recently, it was demonstrated that germylamines R3GeNR’2 were useful reagents for the conversion of acid fluorides to amides. This transformation occurs readily at room temperature and has a low activation energy. In the present study, the versatility of this amidation reaction with aryl acid fluorides is investigated. A series of thirteen acid fluorides with various substituents on the aromatic ring were reacted with the germylamine Ph3GeNMe2 and twelve of these were converted to the corresponding amides in high yields, the exception being 1,4‐benzenedicarbonyl difluoride. The germylamines Bun3GeNMe2 and Pri3GeNMe2 also could be used for this interconversion, and both of these species successfully converted 1,4‐benzenedicarbonyl difluoride to the corresponding amide. In addition, the crystal structure of Ph3GeNMe2 is reported. This represents one of only three crystallographically characterized germylamines. The synthesis and 19F NMR characterization of three fluorogermanes R3GeF (R=Bun, Pri, and Mes) are also reported herein.
The educational experience of young people in residential care through the lens of learning careers
Authors: Marion Élodie , Tchuindibi Laurence
Published: October 2023

To complement previous research investigating the educational attainment of young people in out‐of‐home care reporting lower educational outcomes and risk factors, a more comprehensive approach is necessary. Our objective with this article is to better understand the learning careers of young people in residential care. That includes documenting their experience and the meaning they attribute to learning in formal settings over time and identifying critical turning points in each young person's learning career. Based on an interpretative paradigm, we conducted a qualitative study using biographical interviews with young people aged 14–18 in residential care in Quebec, Canada. We first demonstrate that the learning careers of young people in residential care are unique and non‐linear. Second, by studying turning points, we highlight the critical role that institutions, teachers and youth workers can play in fostering a positive or negative learning career. Finally, we noted learners’ different responses to these circumstances and differences in learners’ perception of their measured performance and their influence on their engagement with formal learning. We discuss why considering young people as the main actors and producers of meaning regarding their educational experience and learning careers appears necessary.
Ecotoxicity characterization assisted performance assessment of electro‐bioremediation reactors for nitrate and arsenite elimination
Authors: Fekete‐Kertész Ildikó , Pous Narcís , Feigl Viktória , Márton Rita , Berkl Zsófia , Ceballos‐Escalera Alba , Balaguer Maria D. , Puig Sebastià , Molnár Mónika
Published: October 2023

The performance of combined reduction of nitrate (NO3−) to dinitrogen gas (N2) and oxidation of arsenite (As[III]) to arsenate (As[V]) by a bioelectrochemical system was assessed, supported by ecotoxicity characterization. For the comprehensive toxicity characterization of the untreated model groundwater and the treated reactor effluents, a problem‐specific ecotoxicity test battery was established. The performance of the applied technology in terms of toxicity and target pollutant elimination was compared and analyzed. The highest toxicity attenuation was achieved under continuous flow mode with hydraulic retention time (HRT) = 7.5 h, with 95%, nitrate removal rate and complete oxidation of arsenite to arsenate.Daphnia magnaproved to be the most sensitive test organism. The results of theD. magnalethality test supported the choice of the ideal operational conditions based on chemical data analysis. The outcomes of the study demonstrated that the applied technology was able to improve the groundwater quality in terms of both chemical and ecotoxicological characteristics. The importance of ecotoxicity evaluation was also highlighted, given that significant target contaminant elimination did not necessarily lower the environmental impact of the initial, untreated medium, in addition, anomalies might occur during the technology operational process which in some instances, could result in elevated toxicity levels.
Dispensary personnel's views and experiences regarding oncologic cannabis and the counsel they offer adults with cancer
Authors: Nayak Manan M. , Chai Peter R. , Tung Stephanie , Tulsky James A. , Hammer Marilyn , Andrade Nicole , Braun Ilana M.
Published: October 2023

Background

A minority of oncologists feel qualified to advise adults with cancer on issues pertaining to medicinal cannabis. Adults with cancer frequently access medicinal cannabis information from non‐medical sources such as cannabis dispensaries. We explored dispensary personnel's views and experiences regarding oncologic cannabis and the counsel they extend individuals with cancer.

Methods

Snowball sampling in this qualitative study facilitated recruitment across 13 states (N = 26). Semi‐structured phone interviews ceased with thematic saturation. A multi‐stage thematic analysis combined inductive and deductive codes.

Results

Of the 26 dispensary personnel interviewed, 54% identified as female and 19% as non‐white. Median age was 40 years. A consensus emerged among participants concerning the botanical's efficacy for cancer‐related symptoms; less so regarding its antineoplastic potential. Principles for serving those with cancer included provision of client‐centered, symptom‐based, and trial‐and‐error approaches. Non‐inhalation modes of administration were generally recommended. No consensus was reached as to whether delta‐9‐tetrahydrocannabinal (THC)‐ or cannabidiol‐predominant products were preferable in this population. Challenges in oncologic advising included successfully identifying individuals with cancer at the dispensary counter, financial toxicity, the special treatment required for the THC‐naïve, and operating in the absence of standardized guidelines.

Conclusions

These informed assertions suggest that members of the oncologic community should grapple with the extent to which they feel comfortable with both the nature and degree of counsel adults with cancer receive through dispensaries.
Correlation between L‐amino acid transporter 1 expression and 4‐borono‐2‐18F‐fluoro‐phenylalanine accumulation in humans
Authors: Kashihara Tairo , Mori Taisuke , Nakaichi Tetsu , Nakamura Satoshi , Ito Kimiteru , Kurihara Hiroaki , Kusumoto Masahiko , Itami Jun , Yoshimoto Seiichi , Igaki Hiroshi
Published: October 2023

Background

The correlation between L‐type amino acid transporter 1 (LAT1) expression and 4‐borono‐2‐18F‐fluoro‐phenylalanine (18F‐FBPA) accumulation in humans remains unclear. This study aimed to investigate the correlation between LAT1 expression in tumor tissues and 18F‐FBPA accumulation in patients with head and neck cancer who participated in a clinical trial of 18F‐FBPA positron emission tomography (PET).

Methods

Altogether, 28 patients with head and neck cancer who participated in a clinical trial of 18F‐FBPA PET at our institution between March 2012 and January 2018 were included. Correlations between standardized uptake values (SUVs); the maximum SUV (SUVmax), the mean SUV within a 1 cm3 sphere centered at a single point, that is, the SUVmax (SUVpeak), the minimum SUV (SUVmin), and the intensity of LAT1 expression (maximum and minimum LAT1 expressions) were investigated.

Results

Weak correlations were identified between SUVmax and LAT1 maximum score, SUVmin and LAT1 maximum score, and SUVmin and LAT1 minimum score (ρ = 0.427, 0.362, and 0.330, respectively). SUVmax and LAT1 minimum score, SUVpeak and LAT1 maximum score, and SUVpeak and LAT1 minimum score demonstrated moderate correlations (ρ = 0.535, 0.556, and 0.661, respectively). Boron neutron capture therapy (BNCT) was performed in 2 of the 4 patients with discrepancies between 18F‐FBPA accumulation and intensity of LAT1 expression, and the intensity of LAT1 expression was a better predictor of treatment response.

Conclusion

18F‐FBPA accumulation and the intensity of LAT1 expression demonstrated a moderate correlation; however, LAT1 expression may be a better predictor of treatment response of BNCT in patients with discrepancies.
Pre‐bariatric surgery acute kidney injury: Can this be prevented?
Authors: Leelaviwat Natnicha , Yingchoncharoen Pitchaporn , Thongpiya Jerapas , Abdelnabi Mahmoud , Mekraksakit Poemlarp
Published: October 2023

Key Clinical Message

Pre‐bariatric surgery dietary recommendations should take into account daily protein intake and other risk factors for kidney injury. This is important because a high protein intake can potentially lead to kidney injury.

Bariatric surgery has been shown to be a highly effective intervention for achieving weight loss and reducing obesity related‐comorbidities. Acute kidney injury (AKI) is considered one of the common complications in perioperative and post‐bariatric surgery. However, pre‐bariatric surgery AKI has never been reported. Several studies demonstrated that pre‐bariatric surgery weight loss improved surgical outcomes and decrease postoperative complications. Some diet regimens have been introduced including low‐caloric diet (LCD), very‐low caloric diet (VLCD), and very‐low caloric ketogenic diet (VLCKD). We present a patient who develops AKI after 10 days of having a high‐protein diet from a pre‐bariatric weight loss strategy.
Transient neonatal pustular melanosis: An unusual and challenging eruption
Authors: Boffa Michelle Marie , Borg Janine , Grech Marie‐Claire , Pace David , Montalto Simon Attard
Published: October 2023

Key Clinical Message

TNPM is a benign, transient, neonatal pustulosis requiring no active treatment. Diagnosis is clinical, characterized by a vesiculopustular eruption, healing with residual hyperpigmented macules. Before diagnosing TNPM, serious conditions including skin infections should be excluded. This case was unusual in that vesiculobullae predominated, with a notable absence of simple pustules.
Silent sinus syndrome: A case report
Authors: Salari Samaneh , Anbiaee Najme , Baee Maryam Bozorgi
Published: October 2023

Key Clinical Message

A 65‐year‐old patient was referred to the Faculty of Dentistry, Mashhad University of Medical Sciences, Mashhad, Iran, with left facial pain and numbness in the upper lip. Based on clinical examinations and radiographic investigations, the patient was diagnosed with silent sinus syndrome. This study discusses oral findings associated with silent sinus syndrome.
A novel mutation c.457C > T p.Q153 in the HMBS gene in a Mexican woman with acute intermittent porphyria
Authors: Malagon‐Rangel Jose , Solis Jose Gabriel , Zavala‐Jonguitud Luis Fernando , Basile‐Alvarez Martín Roberto , Malagon‐Liceaga Andrea
Published: October 2023

Key Clinical Message

The detection of a novel HMBS gene mutation (c.457C > T) in a Mexican woman with acute intermittent porphyria underscores the importance of expanding genetic analyses in diverse populations to improve diagnosis, management, and knowledge of the disease's clinical implications.

Acute intermittent porphyria (AIP) is an autosomal dominant disorder caused by a deficiency in the enzymatic activity of porphobilinogen deaminase (HMBS), resulting in the accumulation of toxic heme metabolites. In this report, we present the case of a Mexican woman with AIP who experienced recurrent episodes of severe abdominal pain, weakness, vomiting, and insomnia. Despite the challenges in diagnosis and treatment, genetic analysis revealed a novel HMBS mutation, c.457C > T (p.Q153X), located in exon 9. This mutation induces a premature translational stop codon and had not been previously reported in medical literature among individuals with AIP. Remarkably, the patient exhibited a positive response to RNA interference therapy. We hypothesize that this novel HMBS mutation may potentially account for the more severe clinical presentation observed in this case. However, further research is necessary to establish a definitive link between this specific mutation and disease severity. The prevalence and genetic variants of AIP in Mexico remain largely unknown, underscoring the importance of conducting additional research and expanding genetic analyses to gain a better understanding of the clinical implications associated with these mutations.
Electronic structure analysis of phthalocyanine complexes using magnetic circular dichroism and magnetic circularly polarized luminescence spectroscopy
Authors: Suzuki Satoko , Santria Anas , Oyama Taiji , Akao Ken‐ichi , Ishikawa Naoto
Published: October 2023

In the study of phthalocyanine complexes using magnetic circular dichroism (MCD) spectroscopy, the electronic structure of excited states is generally discussed based on the rigid‐shift approximation, in which the band profiles for left‐handed circularly polarized (lcp) and right‐handed circularly polarized (rcp) light are assumed to be the same. This assumption may not necessarily be valid for cases where there are multiple initial states having different geometries. Magnetic circularly polarized luminescence (MCPL) from phthalocyanine complexes can be regarded as an example of such cases, since the two degenerate emission states are split in a magnetic field and can undergo a structural deformation. Here, we investigated an alternative approach, where the lcp and rcp components are independently determined. This method, which we refer to as the direct‐separation approach, allows direct determination of the distribution of the two emission states as well as the orbital angular momentum . Using this approach, and the distribution were determined from MCD and MCPL spectra of a series of phthalocyanine complexes. Comparison of the two methods shows that the rigid‐shift and the direct‐separation approaches give practically equivalent results for the systems under study, but the latter is advantageous for systems where the former is not applicable.
Health care utilization by long‐term survivors of blood or marrow transplantation—A Bone Marrow Transplant Survivor Study report
Authors: Oliver Marian M. , Meng Qingrui , Hageman Lindsey , Landier Wendy , Balas Nora , Ross Elizabeth , Francisco Liton , Bosworth Alysia , Te Hok Sreng , Wong F. Lennie , Bhatia Ravi , Forman Stephen J. , Armenian Saro H. , Weisdorf Daniel J. , Bhatia Smita
Published: October 2023

Background

Blood or marrow transplantation (BMT) survivors carry a high burden of morbidity, yet health care utilization by this vulnerable population remains understudied. Patterns and predictors of various domains of health care utilization in long‐term BMT survivors were evaluated.

Methods

Study participants were drawn from the Bone Marrow Transplant Survivor Study (BMTSS). Patients transplanted between 1974 and 2014 at one of three transplant centers who had survived ≥2 years after BMT and were aged ≥18 years at the time of the study were included. A BMTSS survey served as the source of data for health care utilization, sociodemographics, and chronic health conditions. Domains of health care utilization in the 2 years preceding study participation included routine checkups, BMT‐related visits, transplant/cancer center visits, emergency room (ER) visits, hospitalizations, and high health care utilization (≥7 physician visits during the 2 years before the study). Clinical characteristics and therapeutic exposures were abstracted from medical records.

Results

In this cohort of 3342 BMT survivors (52% allogeneic), the prevalence of health care utilization declined over time since BMT for both allogeneic and autologous BMT survivors, such that among those who had survived ≥20 years, only 49%–53% had undergone routine checkups, 37%–38% reported BMT‐related visits, and 28%–29% reported transplant/cancer center visits. The presence of severe/life‐threatening conditions and chronic graft‐vs‐host disease increased the odds of health care utilization across all domains. Lower education, lack of insurance, and Hispanic ethnicity were associated with a lower prevalence of routine checkups and/or transplant/cancer center visits. Lower income increased the odds of ER visits but reduced the odds of hospitalizations or high health care utilization.

Conclusions

This study identified vulnerable populations of long‐term BMT survivors who would benefit from specialized risk‐based anticipatory care to reduce high health care utilization, ER visits, and hospitalizations.
Phenotypic plasticity and genetic trends in the past 30 years of sugarcane genetic improvement in Louisiana
Authors: Baptistella João L. Corte , Blanchard Brayden A. , Taylor Zachary , Kimbeng Collins A. , Fritsche‐Neto Roberto , Gravois Kenneth A. , Reis André F. B.
Published: October 2023

Sugar yield, which results from the combination of stalk biomass (SB) and sugar content (SC), stands as the critical trait for sugarcane breeding programs in Louisiana. Nevertheless, it remains uncertain how SB and SC have individually contributed to the recent increase in sugar yield and how the environment governs their relationship. We applied linear mixed models and the Finlay–Wilkinson model to analyze historical data from the Louisiana outfield variety trials, from plant cane to the third ratoon in multiple environments. The primary objectives were to determine (i) SC and SB genetic gain, (ii) the nature of the relationship between SB and SC, and (iii) whether genotypes are widely or specifically adapted to the environment. Our results showed that the breeding increased sugar yield by relying mostly on SB (0.600–0.652 Mg ha−1 year−1 and 0.893%–0.950% per year) and less on SC (0.371–0.384 kg year−1 and 0.282%–0.292% per year). This was achieved by increasing genotypes SB sensitivity to environmental conditions (0.310% per year) on the plant cane rather than ratoon (nonsignificant). Additionally, the environment strongly controlled the relationship between SB and SC without a significant positive or negative trend on the population mean. From an environmental perspective, high‐yielding environments also provided conditions for high SC on plant cane. Our study highlights that environment characterization is fundamental to sugarcane breeding and emphasizes the opportunity to direct efforts on selecting genotypes that are responsive to the environmental quality by producing superior SB in the ratoon crop cycles.
The influence of state ownership on environmental proactivity: An institutional perspective of international firms
Authors: Bueno‐García Manuel , Ahmadova Gozal
Published: October 2023

The influence of state ownership on a firm's environmental strategy is still unclear due to the varied relationships across different international institutional contexts in the firm's home and host country. Applying mixed effect regression models to a sample of 2997 observations of 298 firms from the MSCI World Index for the period 2007–2018, this paper analyzes the different effects of key institutional factors on this relationship. While a state‐owned firm from a state with a high home country environmental profile will have a more positive effect on a firm's environmental proactivity, internationalization will weaken it, since the firm will encounter higher complexity when translating its green actions into a more global institutional context. In addition, when internationalization involves a very different host country environmental profile, the greater institutional distance seems to modify the influence of state ownership on environmental proactivity. Our results provide key theoretical and practical implications for managers in relation to state‐owned firms' global environmental strategies.
Early CRP kinetics to predict long‐term efficacy of first‐line immune‐checkpoint inhibition combination therapies in metastatic renal cell carcinoma: an updated multicentre real‐world experience applying different CRP kinetics definitions
Authors: Hoeh Benedikt , Garcia Cristina Cano , Banek Severine , Klümper Niklas , Cox Alexander , Ellinger Jörg , Schmucker Philipp , Hahn Oliver , Mattigk Angelika , Zengerling Friedemann , Becker Philippe , Erdmann Kati , Buerk Bjoern Thorben , Flegar Luka , Huber Johannes , Kalogirou Charis , Zeuschner Philip
Published: October 2023

Objectives

Although biomarkers predicting therapy response in first‐line metastatic renal carcinoma (mRCC) therapy remain to be defined, C‐reactive protein (CRP) kinetics have recently been associated with immunotherapy (IO) response. Here, we aimed to assess the predictive and prognostic power of two contemporary CRP kinetics definitions in a large, real‐world first‐line mRCC cohort.

Methods

Metastatic renal carcinoma patients treated with IO‐based first‐line therapy within 5 years were retrospectively included in this multicentre study. According to Fukuda et al., patients were defined as ‘CRP flare‐responder’, ‘CRP responder’ and ‘non‐CRP responder’; according to Ishihara et al., patients were defined as ‘normal’, ‘normalised’ and ‘non‐normalised’ based on their early CRP kinetics. Patient and tumor characteristics were compared, and treatment outcome was measured by overall (OS) and progression‐free survival (PFS), including multivariable Cox regression analyses.

Results

Out of 316 mRCC patients, 227 (72%) were assigned to CRP groups according to Fukuda. Both CRP flare‐ (HR [Hazard ratio]: 0.59) and CRP responders (HR: 0.52) had a longer PFS, but not OS, than non‐CRP responders. According to Ishihara, 276 (87%) patients were assigned to the respective groups, and both normal and normalised patients had a significantly longer PFS and OS, compared with non‐normalised group.

Conclusion

Different early CRP kinetics may predict therapy response in first‐line mRCC therapy in a large real‐world cohort. However, further research regarding the optimal timing and frequency of measurement is needed.
Hypotension in heart failure is less harmful if associated with high or increasing doses of heart failure medication: Insights from the Swedish Heart Failure Registry
Authors: Girerd Nicolas , Coiro Stefano , Benson Lina , Savarese Gianluigi , Dahlström Ulf , Rossignol Patrick , Lund Lars H.
Published: October 2023

Aims

Heart failure (HF) medication may reduce blood pressure (BP). Low BP is associated with worse outcomes but how this association is modified by HF medication has not been studied. We evaluated the association between BP and outcomes according to HF medication dose in HF with reduced ejection fraction (HFrEF).

Methods and results

We studied HFrEF patients from the Swedish HF registry (2000–2018). Associations between systolic BP (SBP) and cardiovascular death (CVD) and/or HF hospitalization (HFH) were analysed according to doses of renin–angiotensin system (RAS) inhibitors, beta‐blockers and mineralocorticoid receptor antagonists (MRA). Among 42 040 patients (median age 74.0), lower baseline SBP was associated with higher risk of CVD/HFH (adjusted hazard ratio [HR] per 10 mmHg higher SBP: 0.92, 95% confidence interval [CI] 0.92–0.93), which was less high risk under optimized RAS inhibitor and beta‐blocker doses (10% decrease in event rates per 10 mmHg SBP increase in untreated patients vs. 7% decrease in patients at maximum dose, both adjusted p < 0.02). Among the 13 761 patients with repeated measurements, 9.9% reported a SBP decrease >10 mmHg when HF medication doses were increased, whereas 24.6% reported a SBP decrease >10 mmHg with stable/decreasing doses. Decreasing SBP was associated with higher risk of CVD/HFH in patients with stable (HR 1.10, 95% CI 1.04–1.17) or decreasing (HR 1.29, 95% CI 1.18–1.42) HF medication dose but not in patients with an increase in doses (HR 0.94, 95% CI 0.86–1.02).

Conclusions

The association of lower SBP with higher risk of CVD/HFH is attenuated in patients with optimized HF medication. These results suggest that low or declining SBP should not limit HF medication optimization.
Nonlinear electrophoresis of nonspherical particles in a rectangular microchannel
Authors: Bentor Joseph , Xuan Xiangchun
Published: October 2023

Nonlinear electrophoresis offers advantageous prospects in microfluidic manipulation of particles over linear electrophoresis. Existing theories established for this phenomenon are entirely based on spherical particle models, some of which have been experimentally verified. However, there is no knowledge on if and how the particle shape may affect the nonlinear electrophoretic behavior. This work presents an experimental study of the nonlinear electrophoretic velocities of rigid peanut‐ and pear‐shaped particles in a rectangular microchannel, which are compared with rigid spherical particles of similar diameter and surface charge in terms of the particle slenderness. We observe a decrease in the nonlinear electrophoretic mobility, whereas an increase in the nonlinear index of electric field when the particle slenderness increases from the peanut‐ to pear‐shaped and spherical particles. The values of the nonlinear index for the nonspherical particles are, however, still within the theoretically predicted range for spherical particles. We also observe an enhanced nonlinear electrophoretic behavior in a lower concentration buffer solution regardless of the particle shape.
A new device for online nanoscale sampling and capillary electrophoresis analysis of plant sap composition
Authors: Melicherová Natália , Gloser Vít , Skalák Jan , Trtílek Martin , Lavická Jana , Foret František
Published: October 2023

In this work, an online sampling of plant xylem sap combined with an efficient (CE)‐based method was developed and applied to study the kinetics of changes in the sap composition and to assess plant fitness under stress conditions comprehensively. A laboratory‐built CE device was developed to provide online sampling and CE analysis of various ionogenic species in the sap during plant stress response. The rapid online sampling and short CE analysis time allow for real‐time monitoring of changes in sap constituents in the living plant during the stress response. The developed device was successfully used to analyze chloride, nitrate, and sulfate ions in the plant xylem during the salt stress or stress caused by nitrate deficiency within short time scales.
A simplified analysis method for estimating the peak responses of recentering structures with viscous damping systems
Authors: Li Junlin , Wang Wei , Kusunoki Koichi , Maida Yusuke , Wang Zelin
Published: October 2023

Recentering structure with a viscous damping system is an emerging structural system with remarkable seismic resilience. This system can exhibit sufficient energy‐dissipating capacity during a major earthquake and eliminate the residual deformation through recentering mechanism afterward. However, the seismic response of the considered system is still confusing due to its complex dynamic behavior. Thus, it is hard to estimate the peak responses of the system during a major earthquake. This study proposes a simplified analysis method for estimating the peak responses of recentering structures with viscous damping systems based on an equivalent two‐stage substitute model. Considering the considerable strain energy of recentering structures during vibrations, this method proposes to employ effective stiffness based on the equal‐energy principle in an equivalent two‐stage substitute model. Based on this concept, corresponding equations are derived for capturing the peak transient responses of the considered system. Results of response history analysis validate that the proposed method can reasonably estimate maximum relative displacement, relative velocity, and absolute acceleration. Given its satisfactory accuracy, this method is promising while conducting seismic design of recentering structures with viscous damping systems.
Rooting performance of cassava cuttings due to the number of nodes and rooting media
Authors: Muktar Halima , Beshir Hussien Mohammed , Tadesse Tesfaye , Haile Ashenafi
Published: October 2023

Cassava is a major food security crop in the developing world, providing a basic diet for over half a billion people. Stem cutting is the major propagation technique in commercial cassava production, despite its limitations in bulkiness and high cost. Research is lacking in optimizing the number of nodes for the most economical use of the planting material. It can be hypothesized that one or two node cuttings can be used in proper rooting media. Hence, a study was conducted to determine the appropriate number of nodes on selected rooting media for better rooting and shoot growth of cassava. A factorial combination of four number nodes (one, two, three, and standard, or 4–6 nodes) and four types of rooting media (sawdust, cocopeat, topsoil, and sand) was used in a completely randomized design with three replications. Nursery and field establishment data were collected. The result revealed that the interaction between the number of nodes and the media significantly (p < 0.05) affected all fresh and dry weights of root and shoot. Sawdust and cocopeat performed best in terms of root number, root length, leaf number, branch number, shoot length, and rooting percentage. Root fresh weight, root dry weight, shoot fresh weight, and shoot dry weight were higher when stem cuttings were planted using two or more nodes on cocopeat or sawdust as compared to planting them on topsoil or sand. The use of two or more nodes on cuttings using cocopeat or sawdust found outstanding results for rooting. However, the standard cutting was better for survival percentage during field establishment. The result confirmed that two nodes of cassava stem cutting are enough for the successful rooting of cassava, and sawdust promotes the rooting of cuttings. Hence, we recommend sawdust as a rooting medium and two or more nodes of stem cuttings of cassava.
Comparison of the effect of hydroxyl propyl methyl cellulose, pectin, and concentrated raisin juice on gluten‐free bread based on rice and foxtail millet flour
Authors: Abdollahzadeh Abolghasem , Vazifedoost Mohsen , Didar Zohreh , Haddadkhodaprast Mohammad Hossein , Armin Mohammad
Published: October 2023

The nutritional and technological challenges of gluten‐free (GF) bread have increased the need for its modification due to the growing demand for this product, especially from celiac patients. Therefore, the present study aims at evaluating the influence of hydroxyl propyl methyl cellulose (HPMC) at 1% and 2% levels, pectin at 1.5% and 2.5% levels, and concentrated raisin juice (CRJ) at 3% and 4% levels on the dough rheological properties and quality of GF bread based on rice and millet flour. The GF bread prepared with HPMC and incorporating CRJ had higher water absorption, dough development time, and dough stability. In addition, the firmness of GF bread during 24–72 h after baking in the presence of 1% HPMC with 3% and 4% CRJ followed by 2.5% pectin incorporating 3% and 4% CRJ showed a significant decrease compared to the control sample. Further, the color index of GF bread was improved with the addition of HPMC and pectin and the L* index decreased in all GF breads with CRJ. The highest volume was occupied by bread containing 1% HPMC. The results demonstrated that GF bread could be produced from a mixture of rice and millet flour and its technological quality was improved by using 1% HPMC and 3% CRJ. Therefore, it has the necessary potential for high‐scale production and consumption among members of the society.
Active compounds from Calendula officinalis flowers act via PI3K and ERK signaling pathways to offer neuroprotective effects against Parkinson's disease
Authors: Zhang Xuanming , Wang Rongchun , Finiuk Nataliya , Stoika Rostyslav , Lin Houwen , Wang Xue , Jin Meng
Published: October 2023

Calendula officinalis flowers, associated with diverse biological effects, could be utilized as functional food ingredients to play a crucial role in human health. In this study, we examined the anti‐PD activity of C. officinalis flower extracts and investigated their bioactive compounds and molecular mechanisms based on LC–MS/MS assay, bioinformatic exploration and in vitro treatment of SH‐SY5Y cells. C. officinalis extracts exhibited significant positive effects on the length and fluorescence density of the dopaminergic neuron region in zebrafish larvae. At 10 μg/mL, the extract restored the length to 96.54% and fluorescence density to 87.77% of the control values, which was equivalent to the effect of a positive drug, indicating the extract's powerful potential to alleviate PD symptoms. Five active compounds, including chlorogenic acid, 3,4‐dicaffeoylquinic acid (DA), rutin, isorhamnetin 3‐O‐glucoside (IG) and calenduloside E (CE) were identified in extracts by LC‐QTOF‐MS/MS. Hsp90α, PI3K and ERK were revealed as core targets of DA, IG and CE in relation to anti‐PD activity. The compounds docked deeply within the pocket region of Hsp90α protein, and their binding energies (∆Gb) were −6.93 kcal/mol (DA), −6.51 kcal/mol (IG) and −3.03 kcal/mol (CE), respectively. Subsequently, they concurrently activated the PI3K/Akt signaling pathway and inhibited the ERK signaling pathway, thereby preventing neuronal death and alleviating neuronal degeneration. These compounds from C. officinalis could be potent nutraceutical agents with protective properties that may shield dopaminergic neurons against the damage caused by PD. Our findings provide a basis for utilizing the C. officinalis flowers in functional foods.
A brief introduction to the detrital zircon U–Pb and Hf isotopic datasets for mainland China and adjacent regions
Authors: Yang Jianghai , Wang Ping , Huang Hu , Hu Xiumian
Published: October 2023

Improvements in analytical technique and data processing lead to a large deposit of detrital zircon U–Pb and Hf isotopic data in published journal articles, thesis and reports. With the support of Deep‐time Digital Earth Big Science Program, OneSediment Project conducted a team‐working effort to assemble the detrital zircon U–Pb and Hf isotopic data for mainland China and adjacent regions. Entity‐relationship diagram was constructed for detrital zircon data to determine what information need to be collected. Researchers and students from 13 institutions were organized together to fulfil this task and generated 13 detrital zircon datasets. The assembled datasets totally include 6635 samples and 560,596 analyses. The samples were checked in terms of lithology and stratigraphy according to the latest stratigraphic framework. Collected detrital zircon U–Pb and Hf isotopic data were recalculated for the best U–Pb age and εHf(t) values. They can be used to track crustal growth, tectonic evolution, provenance analysis and palaeogeographical change in regional and, when combined with other dataset, global scales.
Teachers matter in early childhood: The relation between teacher behaviours and executive function development in toddlerhood
Authors: Koşkulu‐Sancar Sümeyye , Blom Elma , van de Weijer‐Bergsma Eva , Grandfield Elizabeth , Verhagen Josje , Mulder Hanna
Published: October 2023

The current study investigates the role of teacher behaviors in toddlers' executive function development. Teachers' (N = 215) emotional and behavioral support and instructional support were observed through classroom observations when children were 2 years old. Selective attention, verbal short‐term memory, and visuospatial working memory of children (N = 876, 48.4% female) were assessed at age 2 (Mage = 28.60 months, SD = 2.83) and 3 (Mage = 42.38 months, SD = 2.47). Teachers' instructional support positively predicted growth in selective attention, but not verbal short‐term memory or visuospatial working memory. Teachers' emotional and behavioral support did not predict the growth in executive function measures. Findings have implications for understanding the role of teacher‐child interactions in executive function development in toddlerhood.
Brain tumor image pixel segmentation and detection using an aggregation of GAN models with vision transformer
Authors: Datta Priyanka , Rohilla Rajesh
Published: October 2023

A number of applications in the field of medical analysis require the difficult and crucial tasks of brain tumor detection and segmentation from magnetic resonance imaging (MRI). Given that each type of brain imaging provides distinctive information about the specifics of each tumor component, in order to create a flexible and successful brain tumor segmentation system, we first suggest a normalization preprocessing method along with pixel segmentation. Then creating synthetic images is advantageous in many fields thanks to generative adversarial networks (GANs). In contrast, combining different GANs may enable understanding of the distributed features but it can make the model very complex and confusing. Standalone GAN may only retrieve the localized features in the latent version of an image. To achieve global and local feature extraction in a single model, we have used a vision transformer (ViT) along with a standalone GAN which will further improve the similarity of the images and can increase the performance of the model for detection of tumor. By effectively overcoming the constraint of data scarcity, high computational time, and lower discrimination capability, our suggested model can comprehend better accuracy, and lower computational time and also give the understanding of the information variance in various representations of the original images. The proposed model was evaluated on the BraTS 2020 dataset and Masoud2021 dataset, that is, a combination of the three datasets SARTAJ, Figshare, and BR35H. The obtained results demonstrate that the suggested model is capable of producing fine‐quality images with accuracy and sensitivity scores of 0.9765 and 0.977 on the BraTS 2020 dataset as well as 0.9899 and 0.9683 on the Masoud2021 dataset.
Omeprazole: A Comprehensive Review
Authors: Massoomi Firouzan , Savage John , Destache Christopher J.
Published: October 2023

Omeprazole is a member of a new class of substituted benzimidazoles. These agents inhibit the proton pump in the gastric parietal cell, blocking the final step in the gastric acid secretory pathway. Omeprazole has been investigated for the treatment of gastric ulcer, duodenal ulcer, gastroesophageal reflux, and various hypersecretory states. The prolonged inhibition of gastric acid secretion allows for once‐daily dosing in patients with peptic ulcer disease and gastroesophageal reflux, and once‐ or twice‐daily dosing in patients with Zollinger‐Ellison syndrome. Compared with currently available therapies, omeprazole is well tolerated and demonstrates a more rapid ulcer healing rate. It is superior to conventional therapies in the treatment of Zollinger‐Ellison syndrome. Side effects are infrequent when the drug is used for the short‐term management of ulcers.
Clinical Trial Strategies and Future Challenges in the Investigation of Human Congestive Heart Failure
Authors: Leier Carl V.
Published: October 2023

Clinical research in the therapeutics of chronic congestive heart failure (CHF) has evolved from simple case reports and general‐response studies in the 1960s to large, randomized, controlled trials conducted in the late 1980s and 1990s. Cumulatively, the investigations show that angiotensin‐converting enzyme (ACE) inhibitors improve clinical status, exercise capacity, and survival; digoxin augments exercise capacity and, probably, clinical status, with unknown effects on survival; the vasodilator combination hydralazine‐nitrate improves survival, and perhaps clinical status and exercise capacity; and the new vasodilator flosequinan has a favorable effect on clinical status and exercise capacity, but is associated with an increased risk of mortality at 100 mg/day (this agent has subsequently been withdrawn voluntarily by the manufacturer from clinical use). Advances in study design and methodology, combined with the outcomes of major clinical trials, have resulted in new challenges in the investigation of CHF in humans. To date, only the ACE inhibitors have been shown to affect all of the major CHF therapeutic end points in a positive manner. Is it reasonable to expect similar results from all future drug interventions? If not, which end points should be targeted? Must the survival end point be investigated for all CHF drugs under development? Can studies be performed ethically without background ACE inhibitor therapy? Have the optimum duration and methods for therapeutic trials in humans been determined? Should controlled trials of nonhemodynamic and nonneurohormonal interventions (e.g., anticoagulation, magnesium, exercise regimens) be performed? How can the results of clinical trials best be applied in treating the broad range of patients encountered in practice? Despite our increasing sophistication in trial design and methodology, the challenges presented are not fully met by the currently available approaches.
Accuracy of Estimated Creatinine Clearance in Obese Patients With Stable Renal Function in the Intensive Care Unit
Authors: Snider R. Daniel , Kruse James A. , Bander Joseph J. , Dunn Gloria H.
Published: October 2023

We compared agreement between creatinine clearance values in obese, critically ill patients calculated using three common empirically derived formulas and modifications thereof, with creatinine clearance obtained by conventional 24‐hour urine collection. We selected the charts of of 22 patients in intensive care units (86% medical, 14% surgical) according to the following criteria: actual body weight greater than 150% of ideal body weight; serum creatinine variation of less than 15% from the day of starting 24‐hour urine collection to the day before or after the collection; presence of a urinary bladder catheter; no history of renal dialysis; and clinical indication for renal function assessment. Mean measured 24‐hour urinary creatinine clearance for all patients was 72 ± 64 ml/minute (range 8–248 ml/min). The method of estimating creatinine clearance that showed the least mean bias was the equation of Salazar and Corcoran using a corrected serum creatinine concentration (mean bias −2 ml/min); however, the corresponding 95% confidence intervals were wide (‐133‐129 ml/min). The narrowest range of 95% confidence intervals were seen with Jelliffe's equation (mean bias 25 ml/min, 95% confidence intervals −41–90 ml/min). In this sample, estimated creatinine clearances did not agree acceptably with measured values. Despite low mean bias values, none of the empirically derived equations that we studied had clinically acceptable 95% confidence intervals. We recommend using the 24‐hour urine collection method when assessing creatinine clearance in obese, critically ill patients.
Adverse Events After the Abrupt Discontinuation of Paroxetine
Authors: Dominguez Roberto A. , Goodnick Paul J.
Published: October 2023

Paroxetine is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. In contrast to other SSRIs, it has a relatively short half‐life and lacks active metabolites. In three patients the abrupt discontinuation of paroxetine seemed associated with sudden and impairing effects. All three reported marked sleep disturbances and dizziness. They were prescribed the drug for a minimum of 10 weeks, and the maximum dosage was 40 mg/day. All patients experienced rapid remission of symptoms after paroxetine was reintroduced. We failed to observe similar reactions from the abrupt discontinuation at lower dosages. Gradual tapering of the agent for patients receiving more than 20 mg/day is recommended.
Diagnostic and Genetic Issues of Depression and Bipolar Illness
Authors: Berrettini Wade
Published: October 2023

Depression and bipolar illness are the major affective disorders. Various genetic studies indicate the existence of inherited susceptibility factors. Recent linkage studies indicate that loci on chromosomes 18, 21, and X contribute to genetic susceptibility of bipolar illness.