bluuebunny/crossref_metadata_2025 huggingface dataset:
Host‐Variable‐Embedding Augmented Microbiome‐Based Simultaneous Detection of Multiple Diseases by Deep Learning
Authors: Wu Shunyao , Li Zhiruo , Chen Yuzhu , Zhang Mingqian , Sun Yangyang , Xing Jieqi , Zhao Fengyang , Huang Shi , Knight Rob , Su Xiaoquan
Published: September 2023

Microbiome has emerged as a promising indicator or predictor of human diseases. However, previous studies have typically labeled each specimen as either healthy or with a specific disease, ignoring prevalence of complications or comorbidities in actual cohorts, which may confound the microbial–disease associations. For instance, a patient may suffer from multiple diseases, making it challenging to detect their health status accurately. Furthermore, host phenotypes like physiological characteristics and lifestyles can alter microbiome structure, but such information has not yet been fully utilized in data models. To address these issues, a highly explainable deep learning (DL) method called Meta‐Spec is proposed. Using a deep neural network (DNN)‐based approach, it encodes and embeds refined host variables with microbiome features, enabling the detection of multiple diseases simultaneously. Experiments show that Meta‐Spec outperforms regular machine learning (ML) strategies for multilabel disease screening in several cohorts. More importantly, Meta‐Spec successfully detects comorbidities that are often missed by other approaches. In addition, for its high interpretability, Meta‐Spec captures key factors that shape disease patterns from host variables and microbes. Hence, these efforts improve the feasibility and sensitivity of microbiome‐based disease screening in practical scenarios, representing a significant step toward personalized medicine and better health outcomes.
Reversible Boron‐Insertion into Aromatic C−C Bonds
Authors: Kuroki Kaito , Ito Tatsuyoshi , Takaya Jun
Published: September 2023

Formation of borabicyclo[3.2.0]heptadiene derivatives was achieved via boron‐insertion into aromatic C−C bonds in the photo‐promoted skeletal rearrangement reaction of triarylboranes bearing an ortho‐phosphino substituent (ambiphilic phosphine‐boranes). The borabicyclo[3.2.0]heptadiene derivatives were fully characterized by NMR and X‐ray analyses. The dearomatized products were demonstrated to undergo the reverse reaction in the dark at room temperature, realizing photochemical and thermal interconversion between triarylboranes and boron‐doped bicyclic systems. Experimental and theoretical studies revealed that sequential two electrocyclic reactions involving E/Z‐isomerization of an alkene moiety proceed via a highly strained trans‐borepin intermediate.
Canola meal valorization via acid hydrolysis to generate free amino acids
Authors: Warnakulasuriya Sumudu N. , Tanaka Takuji , Wanasundara Janitha P. D.
Published: September 2023

This study investigated an alternative approach to valorizing canola proteins by hydrolyzing them to generate amino acids (AAs). Pre‐treatment of cold‐pressed (CP) cake and desolventized‐toasted (DT) meal with ethanol (99%, vol/vol) followed by protein separation was studied as process optimizations to maximize protein recovery with higher purity. The optimum ethanol pre‐treatment conditions to achieve a meal containing less than 1% oil was reached at a meal‐to‐ethanol ratio of 1:4 (wt:wt) and 50°C for 30 min extraction. The protein recovery reached the maximum at pH 12 and a meal‐to‐solvent ratio of 1:10 (wt:vol), yielding 73% and 33% recovery from ethanol pre‐treated CP and DT meals, respectively, in a single extraction. Untreated and ethanol pre‐treated meals were hydrolyzed with 6 N HCl (protein‐to‐acid ratio of 5 mg:2 mL) for 24 h at 110°C. The ethanol pre‐treatment improved AA recovery and released 373 mg AA/g dry CP meal biomass (dbm) compared to 279 mg AA/g untreated CP cake dbm. However, no improvement in AA recovery upon ethanol pre‐treatment of DT meal. Sulfuric acid was examined as an alternative acid. More than 700 mg AA/g CP protein were released with 6 N H2SO4, while for DT meal proteins, a 10 N concentration was needed to achieve a closer value. Commercial canola meals can be utilized for generating free AAs; however, the meal processing history may affect the yield.
Simulation study on mass transfer characteristics and disk structure optimization of a rotating disk reactor with high viscosity region
Authors: Chen Xupeng , Sun Jianfei , Wu Jintao , Zhang Yaxin , Yin Jianzhong
Published: September 2023

Due to the excellent film‐forming specific surface area of the disk reactor, its application in the polymer devolatilization process can greatly improve the devolatilization performance of the equipment. In view of this, the fluid volume function method in computational fluid dynamics is used to simulate the film forming performance and surface renewal performance in high viscosity zone of disk reactor. In the disk window area, the liquid film thickness becomes thinner and the surface update frequency becomes faster, indicating that the disk window has a positive effect. The devolatilization performance of five new disk structures under different operating conditions is compared and analyzed. It was found that the influence of liquid level height on film area was greater than that of viscosity and rotation speed, the porous sector disk has excellent surface renewal performance and the baffle can achieve better mass transfer efficiency at a distance of 45–60 mm from the disk.
A narrative review of exercise dose during pregnancy
Authors: Claiborne Alex , Jevtovic Filip , May Linda E.
Published: September 2023

The current recommendations for prenatal exercise dose align with those from the American College of Sports Medicine; 150 min of moderate intensity every week of pregnancy. However, recent works suggest there may be a dose‐dependent beneficial effect for mother and offspring; maternal and offspring health outcomes respond differently to low, medium, and high doses of prenatal exercise. It is, therefore, our aim to summarize the published evidence (years 1950–2023) for five metrics of prenatal exercise training commonly reported, that is, “FITT‐V”: Frequency (number of sessions), Intensity (metabolic equivalents “METs”), Time (duration of sessions), Type (exercise mode), Volume (exercise MET*mins). The target audience includes clinicians and health care professionals, as well as exercise professionals and physiologists. Data suggest that moderate exercise frequency (3–4 times weekly) appears safe and efficacious for mother and offspring, while there is contradictory evidence for the safety and further benefit of increased frequency beyond 5 sessions per week. Moderate (3–6 METs) and vigorous (>6 METs) intensity prenatal exercise have been shown to promote maternal and offspring health, while little research has been performed on low‐intensity (<3 METs) exercise. Exercise sessions lasting less than 1 hr are safe for mother and fetus, while longer‐duration exercise should be carefully considered and monitored. Taken together, aerobic, resistance, or a combination of exercise types is well tolerated at medium‐to‐high volumes and offers a variety of type‐specific benefits. Still, research is needed to define (1) the “minimum” effective dose of exercise for mother and offspring health, as well as (2) the maximum tolerable dose from which more benefits may be seen. Additionally, there is a lack of randomized controlled trials addressing exercise doses during the three trimesters of pregnancy. Further, the protocols adopted in research studies should be more standardized and tested for efficacy in different populations of gravid women.
Routine outcome monitoring (ROM) and feedback in university student counselling and mental health services: Considerations for practitioners and service leads
Authors: Barkham Michael , Broglia Emma ,   The SCORE Consortium
Published: September 2023

Aim

Routine outcome monitoring (ROM), including the use of feedback, has become a much vaunted method in psychological therapies but is little used in university/college counselling and mental health services, perhaps because its adoption raises questions for many practitioners and service leaders. There is a need for both clinical‐ and research‐based statements to clarify the reasoning and rationale for ROM. This paper aims to present and respond to common challenges of and reservations about using ROM in student counselling and/or mental health services.

Method

The article poses 15 questions and issues about the adoption of ROM drawn from the literature on this topic and further refined by practitioner‐ and researcher‐members of a consortium comprising service leads, practitioners, and researchers working in the field of student counselling in the UK. The questions address nine themes: (1) the purpose and yield of ROM; (2) the burden of measurement; (3) the impact on clients and process of therapy; (4) consistency with therapeutic theory; (5) client groups and settings; (6) concern from practitioners; (7) equality, diversity, and inclusion; (8) implementation; and (9) relationship with the paradigm of practice‐based evidence.

Findings

Responses to each of the 15 questions are provided from a methodological, evidence‐based, and clinical perspective.

Conclusions

The responses provide practitioners with the necessary information to enable them to make informed decisions as to the value, or otherwise, of adopting ROM, including feedback, in the delivery of counselling interventions, and generating evidence created from clinical practice.
Anterior graft migration in posterior lumbar interbody fusion: A case report and literature review
Authors: Hashimoto Masanori , Hirata Hirohito , Tsukamoto Masatsugu , Tomohito Yoshihara , Mawatari Masaaki , Morimoto Tadatsugu
Published: September 2023

Key Clinical Message

Spine surgeons should be aware of the possibility of anterior displacement of the grafted bone during PLIF and the potential for severe complications that may arise because of such displacement so that preparations can be made for a proper response.

We report two cases of anterior displacement of the grafted bone after posterior lumbar interbody fusion (Graphical Abstract A‐D). The patients did not require additional surgery. The anterior migration of grafted bone or cage can cause damage to anterior organs and blood vessels. Therefore, a careful surgical procedure is necessary.
Anesthetic management of a pediatric patient with methylmalonic acidemia combined with hyperhomocysteinemia: A case report
Authors: Pang Yunting , Meng Fanqing , Guo Yaqiu , Zhou Feng
Published: September 2023

Key Clinical Message

Methylmalonic acidemia (MMA) combined with hyperhomocysteinemia is an autosomal recessive genetic disease which can lead to metabolic acidosis, elevated lactate, and high blood ammonia level. This anesthetic management was mainly how to maintain the stable state of perioperative physiological metabolism of such patients.
Endocardial pacing in a single‐ventricle patient with tricuspid atresia—a case report
Authors: Yamini‐Sharif Ahmad , Yaghoobian Ramin , Ghaderian Homa , Moosavi Najme‐Sadat
Published: September 2023

Key Clinical Message

The use of endocardial pacing in patients with univentricular hearts and intracardiac shunts is limited, primarily due to the increased risk of thromboembolism. However, when accompanied by proper long‐term anticoagulation therapy, it may be safer than epicardial interventions in selected patients at high risk for surgery.

We report transvenous endocardial pacing through the atrial septal defect in a patient with tricuspid atresia, transposition of the great arteries, severe pulmonary hypertension, and complete heart block. This study is among the first reported cases using this pacing method in a patient with a univentricular heart and intracardiac shunt.
Liquid‐Liquid Phase Equilibrium of Glycerolysis Precursors: Experimental and Modeling Study
Authors: Mamtani Kapil , da Silveira Christian L. , Farid Mohammed M. , Shahbaz Kaveh
Published: September 2023

The mutual immiscibility of glycerol and free fatty acids limits glycerolysis, a reaction capable of upgrading waste‐derived oils. In the present work, the liquid‐liquid phase equilibrium data for the glycerol‐water‐oleic acid and glycerol‐monoolein‐oleic acid ternary systems were determined experimentally and compared with predictions of the UNIFAC‐LLE and COSMO‐SAC models. Monoolein was found to affect the glycerol solubility in oleic acid strongly. None of the models investigated adequately determined phase equilibria for the glycerol‐monoolein‐oleic acid system. COSMO‐SAC predictions showed the best trend for glycerol solubility in the fatty phase. For the glycerol‐water‐oleic acid system, UNIFAC‐LLE predictions were in good agreement with experimental data.
Nickel‐Electrocatalyzed Synthesis of Bifuran‐Based Monomers
Authors: Oksanen Valtteri , Rautiainen Sari , Wirtanen Tom
Published: September 2023

Bifuran motifs can be accessed with nickel‐bipyridine electrocatalyzed homocouplings of bromine‐substituted methyl furancarboxylates, which, in turn, can be prepared from hemicellulose‐derived furfural. The described protocol uses sustainable carbon‐based graphite electrodes in the simplest setup – an undivided cell with constant current electrolysis. The reported method avoids using a sacrificial anode by employing triethanolamine as an electron donor.
Highly Electrophilic Intermediates in the Bypass Mechanism of Glutathione Peroxidase: Synthesis, Reactivity, and Structures of Selenocysteine‐Derived Cyclic Selenenyl Amides
Authors: Masuda Ryosuke , Karasaki Takafumi , Sase Shohei , Kuwano Satoru , Goto Kei
Published: September 2023

Selenocysteine (Sec)‐derived cyclic selenenyl amides, formed by the intramolecular cyclization of Sec selenenic acids (Sec–SeOHs), have been postulated to function as protective forms in the bypass mechanism of glutathione peroxidase (GPx). However, their chemical properties have not been experimentally elucidated in proteins or small‐molecule systems. Recently, we reported the first nuclear magnetic resonance observation of Sec–SeOHs and their cyclization to the corresponding cyclic selenenyl amides by using selenopeptide model systems incorporated in a molecular cradle. Herein, we elucidate the structures and reactivities of Sec‐derived cyclic selenenyl amides. The crystal structures and reactions toward a cysteine thiol or a 1,3‐diketone‐type chemical probe indicated the highly electrophilic character of cyclic selenenyl amides. This suggests that they can serve not only as protective forms to suppress the inactivation of Sec–SeOHs in GPx but also as highly electrophilic intermediates in the reactions of selenoproteins.
DNA Chimeras as Electrochemical Biosensors for Host‐Guest Measurements in Blood
Authors: d'Astous Élodie V. , Dauphin‐Ducharme Philippe
Published: September 2023

Few sensing platforms have become ubiquitous to enable rapid and convenient measurements at the point‐of‐care. Those, however, are “one‐off” technologies, meaning that they can only detect a single target and are hardly adaptable. In response, we plan to develop a sensing platform that can be extended to detect other classes of molecules and that affords rapid, convenient, continuous measurements directly in undiluted complex matrices. For this, we decided to rely on a host molecule that presents reversible interactions toward specific guest molecules to develop a new class of sensors that we coined “Electrochemical DNA‐host chimeras”. As a proof‐of‐concept for our sensor, we decided to use cyclobis(paraquat‐p‐phenylene) (“blue box”) that we attached on an electrode‐bound DNA to allow measurements of electron‐rich guests such as dopamine and aspirin. Doing so allows to promote host‐guest complex that could be quantified using blue box's electrochemistry. Because of this unique sensor architecture, we achieve, to our knowledge, the first reagentless, continuous and rapid (<5 min) host‐guest measurements in undiluted whole blood. We envision that given the library of electroactive host molecules that this will allow the development of a sensing platform for measurements of several classes of molecules in complex matrices at the point‐of‐care.
Color and luminance processing in V1 complex cells and artificial neural networks
Authors: Bun Luke M. , Horwitz Gregory D.
Published: September 2023

Object recognition by natural and artificial visual systems benefits from the identification of object boundaries. A useful cue for the detection of object boundaries is the superposition of luminance and color edges. To gain insight into the suitability of this cue for object recognition, we examined convolutional neural network models that had been trained to recognize objects in natural images. We focused specifically on units in the second convolutional layer whose activations are invariant to the spatial phase of a sinusoidal grating. Some of these units were tuned for a nonlinear combination of color and luminance, which is broadly consistent with a role in object boundary detection. Others were tuned for luminance alone, but very few were tuned for color alone. A literature review reveals that V1 complex cells have a similar distribution of tuning. We speculate that this pattern of sensitivity provides an efficient basis for object recognition, perhaps by mitigating the effects of lighting on luminance contrast polarity. The absence of a contrast polarity‐invariant representation of color alone suggests that it is redundant with other representations.
Application of novel phytosorbent to sequester chromium(VI) and lead(II) from aqueous phase: Optimization, equilibrium and kinetics
Authors: Singh Mohini , Rayaz Mohd. , Rao Arti
Published: September 2023

This study investigates the potential of Prosopis cineraria leaf powder (PCLP) as a biosorbent for removing heavy metal ions (HMIs) from aqueous solutions. The biosorption characteristics of PCLP were evaluated with respect to pH, contact time, initial concentrations, and biosorbent dosage. Equilibrium data were analyzed using Langmuir, Freundlich, Temkin, and Dubinin‐Radushkevich (D‐R) isotherm models. Langmuir isotherm demonstrated monolayer adsorption for Cr(VI) (R2 = 0.9876) and Pb(II) (R2 = 0.9990), with maximum adsorption capacities of 10.046 and 10.238 mg g−1, respectively. Kinetic analysis showed a good fit to the pseudo‐second‐order (PSO) model, with R2 values of 0.9979 for Cr(VI) and 0.9821 for Pb(II), indicating that H‐bonding and electrostatic interactions were the dominant adsorption mechanisms. Additionally, non‐linear regression analysis was performed to determine the best‐fitting equilibrium model and compared with linear isotherm and kinetic models. The results confirmed that the nonlinear method outperformed the linear method in isotherm analysis. Specifically, the nonlinear Temkin isotherm model exhibited stronger correlation with the experimental data, making it the most suitable model for fitting the equilibrium data. Conversely, the non‐linear pseudo‐second‐order models yielded comparable goodness of fit to the linear kinetic analysis results. Overall, the findings highlight PCLP as a promising, environmentally friendly, and cost‐effective biosorbent for the removal of toxic HMIs, contributing to sustainable environmental management.
Regulating Consumption for Sustainability? Why the European Union Chooses Information Instruments to Foster Sustainable Consumption
Authors: Pollex Jan
Published: September 2023

In light of ever increasing usage of natural resources, the global discourse on sustainable development is increasingly emphasizing the crucial role of sustainable consumption and thus the contribution of individual consumers—rather than the traditionally focused corporate producers—to the protection of ecosystems. This paper investigates how the European Union (EU) addresses and characterizes consumers and how the framing of the consumers’ role impacts on the design of sustainable consumption policy. Thus, this paper analyzes the relevance of target groups and their discursive construction for policymaking. Based on the analysis of central EU policy agendas providing the frame for consumer‐oriented environmental policy, the paper shows that the EU's sustainable consumption policy builds on an image of average‐rational consumers and a weak sustainable consumption perspective. Both constructions of reality subsequently frame the choice of soft policy instruments. The role of citizens (as opposed to only producers) and the image of average‐rational consumers who can be activated through information measures or incentives gained prominence in the EU—and in OECD countries generally—at a time of dissatisfaction with the performance of regulatory policy in the 1990s, hinting at the significance of contextual factors in understanding discursive shifts with their policy implications.
The Utilization of Expert Knowledge in Times of Crisis: Budgetary and Migration Policies in the Netherlands
Authors: van Nispen Frans K. M. , Scholten Peter W. A.
Published: September 2023

Times of crisis, such as the financial and economic crisis and, more recently, the migration crisis, open windows of opportunity for agenda setting and policy change. However, the added value of policy analysis and utilization‐focused evaluation is often more contested during crises: do crises provide opportunities for the utilization of expert knowledge and policy learning in order to punctuate policy deadlocks and to induce policy innovation or do crises rather inhibit opportunities for the utilization of expert knowledge and policy learning because of political contestation and establishment of a clear political primacy? Building on empirical data drawn from the Dutch comprehensive spending reviews (2010), advisory reports and policy studies, respectively, in the field of the Dutch migration and integration policy (2000–2015), we found that the utilization of expert knowledge is not much different in bad times than in good times. Rather, the type of expert knowledge as well as the way of utilization of expert knowledge is subject to change as boundary organizations are playing a key role as producers of expert knowledge in legitimating policy actors and structures and substantiating policy decisions. We conclude that expert knowledge may be a very important and powerful tool for policy coordination, precisely in the highly contested and politicized setting of a crisis.
Networks of internationalizing digital platforms in physical place and digital space
Authors: Galkina Tamara , Atkova Irina , Ciulli Francesca
Published: September 2023

Research Summary

The existing literature provides contradictory evidence on how digital platform firms establish network relations for internationalization. Some studies argue that they all but obviate the need for traditional relations in physical places. Others argue that these firms can suffer from overreliance on online interactions in digital space. We examine the coexistence of the network relations of international digital platform firms in physical place and digital space. Our multiple‐case study identifies three coexistence mechanisms: reinforcement, separation, and simulation. These mechanisms are conditioned by three respective modes of bordering between physical place and digital space: soldering, interosculation, and division. We contribute to the network approach to internationalization and formulate implications for the concepts of location and borders in international business.

Managerial Summary

International digital platform firms establish traditional network relations in physical places and rely heavily on online interactions in digital space. However, how do they combine their networking activities in these two localities? We examine the coexistence of the network relations of international digital platform firms in physical place and digital space and identify three coexistence mechanisms: reinforcement, separation, and simulation. These mechanisms are conditioned by three respective modes of bordering between physical place and digital space: soldering, interosculation, and division. We show that international platform companies, despite being digital in nature, are well advised to pay attention to not only digital but also actual physical networking, and that they come to see these as mutually nurturing.
Number of positive lymph nodes is superior to neck stage of the 8th AJCC in predicting prognosis in parotid mucoepidermoid carcinoma
Authors: Li Wenlu , Yu Wenli , Cao Haifei , Zhang Aolin
Published: September 2023

Background

To clarify the impact of the number of positive lymph nodes (LNs) on the prognosis of parotid mucoepidermoid carcinoma (MEC).

Methods

Patients who underwent neck dissection for parotid MEC were retrospectively enrolled. The primary outcome variable was overall survival (OS). Associations between OS and LN factors, including the AJCC N stage, intraparotid LN metastasis, number of positive LNs, LN size, and extranodal extension (ENE), were evaluated using Cox proportional hazard regression analyses.

Results

A total of 720 patients were included with a mean age of 56 ± 16 years. There was no additional survival compromise until two positive LNs were presented. After adjusting for the number of positive LNs, intraparotid LN metastasis, ENE, and LN size were not related to prognosis. Our proposed N stage based on the number of metastatic LNs (0/1 vs. 2–4 vs. 5+) showed a superior C‐index to the AJCC N stage in OS prediction.

Conclusion

Quantitative LN burden was an important determinant of prognosis, and the proposed N stage provided better OS stratification than the AJCC N stage.
A nationwide analysis of salvage surgery for laryngeal cancer in the elderly
Authors: Raad Richard A. , Holland Katie , Ritz Ethan M. , Tajudeen Bobby A. , Al‐Khudari Samer , Stenson Kerstin , Teitcher Joshua , Fidler Mary Jo , Jelinek Michael , Joshi Nikhil , Bhayani Mihir K.
Published: September 2023

Background

We aim to describe outcomes of elderly patients undergoing salvage surgery for laryngeal cancer and to characterize the interplay of age with various other factors in this growing population.

Methods

Using the National Cancer Database, we identified cases of salvage laryngectomy in patients who failed chemoradiation. An age cutoff of 70 years was used to separate subjects into two groups. Various factors were compared.

Results

Of the 825 patients included, 166 (20.1%) were elderly. Elderly patients had worse overall survival (p = 0.001), higher 30‐day and 90‐day mortality (p = 0.006, p < 0.001), and a longer length of stay (LOS) (p = 0.015). LOS over 1 week was associated with worse survival (p = 0.032).

Conclusion

Elderly patients had worse overall perioperative survival than their younger counterparts. LOS and 30‐day readmissions were associated with higher risk of mortality in this group. We provide a contemporary set of relevant information for head and neck cancer providers to consider in this growing population
Effect of channel bed sediment on the transport behaviour of superparamagnetic silica encapsulated DNA microparticles in open channel injection experiments
Authors: Tang Yuchen , van Rhijn Fay , Abdelrady Ahmed , Foppen Jan Willem , Bogaard Thom
Published: September 2023

Recently, superparamagnetic silica encapsulated DNA microparticles (SiDNAFe) were designed and in various experiments used as a hydrological tracer. We investigated the effect of bed characteristics on the transport behaviour and especially the mass loss of SiDNAFe in open channel injection experiments. Hereto, a series of laboratory injection experiments were conducted with four channel bed conditions (no sediment, fine river sediment, coarse sand, and goethite‐coated coarse sand) and two water qualities (tap water and Meuse water). Breakthrough curves (BTCs) were analysed and modelled. Mass loss of SiDNAFe was accounted for as a first‐order decay process included in a 1‐D advection and dispersion model with transient storage (OTIS). SiDNAFe BTCs could be adequately described by advection and dispersion with or without a first‐order decay process. SiDNAFe mass recoveries exhibited a wide range, varying from 50% to 120% from sediment‐free conditions to coarse (coated) sediment. In 6 out of 8 cases, SiDNAFe mass recovery was complete. Retention of SiDNAFe was 1–2 orders of magnitude greater than gravitational settling rates, as determined in Tang et al. (Hydrological Processes, e14801, 2023). We reason this was due to grain‐scale hyporheic flows and coupled water‐sediment‐particle interactions. The dispersive behaviour of SiDNAFe generally mimicked that of NaCl tracer. We concluded that SiDNAFe can be used in tracing experiments. However, water quality and sediment characteristics may affect the fate of SiDNAFe in river environments. SiDNAFe is a promising tool for particulate multi‐tracing in large rivers.
Safety and efficacy of mesenchymal stem cells in COVID‐19 patients: A systematic review and meta‐analysis
Authors: Yan Cai , Hu Minjie , Dai Rongjuan
Published: September 2023

Background

Coronavirus disease‐19 (COVID‐19) is a zoonotic disease that has become a global pandemic. The fast evolution of the COVID‐19 pandemic and persist problems make COVID‐19 highly infectious; publicly accessible literature and other sources of information continue to expand in volume. The mesenchymal stem cells (MSCs) therapy efficacy for COVID‐19 is debatable.

Objective

This systematic review and meta‐analysis (SRMA) aimed to evaluate the usefulness of MSCs in treating COVID‐19.

Methods

Relevant publications were retrieved from databases up to April 30, 2022. In the case of dichotomous data, the 95% confidence intervals (CIs) and pooled risk ratio (RR) were estimated with a random effects model (REM) or fixed effects model (FEM). The pooled mean difference (MD) and 95% CIs were calculated with REM or FEM in continuous data. In the outcomes, studies with insufficient or unusable data were reported descriptively.

Results

A total of eight randomized controlled trials (RCTs) with 464 people were chosen for this SRMA. Relative to the control group, mortality was significantly lower in the MSCs group (RR: 0.66, 95% CI: 0.44, 0.99, Z = 2.01, p = .04); other secondary outcomes, such as the clinical symptom improvement rate improved in the MSCs group (RR: 1.44, 95% CI: 1.05, 1.99, Z = 2.24, p = .03), clinical symptom improvement time (MD: −4.01, 95% CI: −6.33, −1.68, Z = 3.38, p = .0007), C‐reactive protein (CRP) (MD: −39.16, 95% CI: −44.39, −33.94, Z = 14.70, p < .00001) and days to hospital discharge (MD: −3.83, 95% CI: −6.19, −1.48, Z = 3.19, p = .001) reduced significantly in MSCs group. However, the adverse reaction incidence did not change significantly.

Conclusions

MSCs are a viable therapy option for COVID‐19 because of their safety and potential efficacy. With no significant adverse effects, MSCs can reduce mortality, clinical symptom improvement time, and days to hospital discharge, improve clinical symptoms, and reduce inflammatory cytokines CRP in COVID‐19. However, further high‐quality clinical studies are required to confirm these results.
Cardiac troponin as a prognosticator of mortality in patients with sepsis: A systematic review and meta‐analysis
Authors: Zheng Peiqiu , Wang Xing , Guo Tao , Gao Wei , Huang Qiang , Yang Jie , Gao Hui , Liu Qian
Published: September 2023

Background

The impact of cardiac troponin on the short‐term and long‐term prognosis of patients with sepsis remains uncertain. Therefore, we conducted a meta‐analysis to investigate the role of cardiac troponin as a potential indicator for sepsis mortality.

Methods

We performed a comprehensive search for articles published before November 2022 using Google Scholar, PubMed, and Web of Science. Inclusion criteria for the studies were: (1) investigation of cardiac troponin, and (2) investigation of sepsis. Exclusion criteria included: (1) inability to obtain or calculate hazard ratio (HR) and 95% confidence interval (CI) for the relationship between cardiac troponin level and sepsis mortality, and (2) reviews, meta‐analyses, and case reports. Analysis of HRs and 95% CIs for the association between cardiac troponin level and sepsis mortality was conducted using STATA 12.0 software.

Results

Our study included 24 prospective studies (comprising 20,457 sepsis patients) and 4 retrospective studies (comprising 1416 sepsis patients). Meta‐analysis demonstrated that elevated cardiac troponin levels were significantly associated with increased sepsis mortality using a random effects model (HR = 1.57, 95% CI 1.41−1.75). Moreover, elevated cardiac troponin levels were also significantly associated with increased hospital mortality of sepsis (HR = 1.35, 95% CI 1.19−1.53) and long‐term mortality of sepsis (HR = 1.96, 95% CI 1.51−2.55) using the random effects model.

Conclusions

Overall, our finding revealed that elevated cardiac troponin for sepsis patients was a predictor of hospital and long‐term mortality. Clinicians may treat septic patients with elevated cardiac troponin more cautious to avoid extra death. Moreover, large clinical studies are warranted to validate this association.
Fertility‐sparing approach to malignant ovarian germ cell tumors – Oncologic and obstetric outocome: A retrospective study
Authors: Ayhan Ali , Tunç Mehmet , Akıllı Hüseyin , Haberal Nihan , Haberal Ali
Published: September 2023

Objective

To evaluate oncologic (such as disease‐free and overall survival) and obstetric outcomes in patients diagnosed with malignant ovarian germ cell tumors (MOGCTs).

Methods

Patients diagnosed with MOGCTs between March 2007 and February 2022 were evaluated and patients who underwent fertility sparing surgery were included in this retrospective study. The obstetric and oncologic outcomes were evaluated by collecting data up until the patient's last follow‐up visit from the hospital records and patient files. The study was approved by Başkent University Institutional Review Board (KA23/124).

Results

Seventy FSS patients were included in this study. The median age of the patients was 22.5 years (range: 11–37). The median follow‐up time was 92.0 months (10–189). Immature teratoma was the most common histological subtype (32.9%). Bilateral involvement was detected in only one patient with immature teratoma (1.4%). The 5‐year DFS rates of immature teratoma, dysgerminoma, yolk sac, and mixed germ cell histologic types were 91.1%, 94.1%, 82.4%, and 88.9%, respectively (P: 0.716).

The 5‐year OS rates of the same histologic types were 95.7%, 100%, 88.2%, and 88.9%, respectively (P = 0.487). All patients (100%) had a regular menstrual cycle after the completion of adjuvant treatment. The mean time between the last chemotherapy and menstruation was 4.38 months. To date, a total of 34 patients tried to conceive after the completion of disease treatment. A total of 23 (67.6%) patients conceived, resulting in 27 live births in 22 (100%) patients.

Conclusion

Fertility preservation should be the first treatment option in MOGCTs in young patients due to the unilateral involvement of the disease and its chemosensitive nature.
Problems and Opportunities in Regulation of Benzodiazepines
Authors: Woods James H.
Published: September 2023

A commentary on current national and international regulation of benzodiazepine‐like drugs is presented. The policies and decision making associated with these regulations also are discussed, both in terms of historical mistakes and current problems. Finally, a proposal is made to improve the methods by which regulations are put into effect.
A model program for pharmacist‐managed healthcare delivery: A tixagevimab–cilgavimab (EVUSHELD) clinic at a Veterans Affairs healthcare system
Authors: Buehrle Deanna J. , Shields Jenna , Lopez Marcos , Mascara Gerard P. , Coppler Tami , Mobayed Leeanne , Clancy Cornelius J.
Published: September 2023

Background

Pharmacists are under‐utilized as caregivers who can improve patients' access to medical treatments. In this study, effectiveness of a multidisciplinary pharmacist‐managed clinic in delivering tixagevimab–cilgavimab pre‐exposure coronavirus disease 2019 (Covid‐19) prophylaxis was determined.

Methods

An observational study at the Veterans Affairs (VA) Pittsburgh Healthcare System tixagevimab–cilgavimab clinic from January 1, 2022 to January 1, 2023 was conducted. Pharmacists identified immunocompromised Veterans system‐wide, performed active (telephone) or passive (mail) outreach to those in three highest‐risk categories and a more moderate‐risk category, respectively, and prescribed and dispensed tixagevimab–cilgavimab.

Results

Eligible Veterans were stratified into Categories 1 (highest‐risk; 18% [193/1089]), 2 (2% [18/1089]), 3 (17% [188/1089]), or 4 (most moderate‐risk; 63% [690/1089]). Most common underlying conditions were rheumatologic (33%, 356/1089), oncologic (20%, 214/1089), and organ transplantation (18%, 197/1089). Twenty five percent (268/1089) of patients received ≥1 tixagevimab–cilgavimab dose. Acceptance in Categories 1–3 was 63% (121/193), 78% (14/18), and 37% (70/188), respectively (51% overall). Acceptance in Category 4 was 9% (63/690; p < 0.0001 vs. Categories 1–3). To put data into context, <2% of immunosuppressed persons in the United States were reported to receive tixagevimab–cilgavimab. Acceptance was greater among Veterans with rheumatologic or oncologic diseases than those with transplant‐related or neurologic diagnoses (p < 0.0001), and among Covid‐19‐vaccinated versus non‐vaccinated Veterans (27% [261/952] and 5% [7/137], p < 0.0001). Six percent (15/268) and 5% (42/821) of treated and untreated patients, respectively, were subsequently diagnosed in‐system with Covid‐19.

Conclusions

A pharmacist‐managed clinic effectively delivered tixagevimab–cilgavimab to immunocompromised Veterans, in particular those at highest Covid‐19 risk. This program is a model for pharmacist‐led clinics for other therapeutics or diseases.
FXII contact activation products have an inhibitory effect on αFXIIa
Authors: Xu Li‐Chong , Siedlecki Christopher A.
Published: September 2023

It is accepted that the contact activation complex of the intrinsic pathway of blood coagulation cascade produces active enzymes that lead to plasma coagulation following biomaterial contact. In this study, FXII was activated through contact with hydrophilic glass beads and hydrophobic octadecyltrichlorosilane‐modified glass beads from neat buffer solutions. These FXII contact activation products generated from material interaction were found to suppress the procoagulant activity of exogenous αFXIIa, and this inhibition was dependent on surface wettability and the concentration of exogenous αFXIIa. Higher relative inhibition rates were generally observed at low concentrations of αFXIIa (1–2 μg/mL) while both hydrophobic and hydrophilic materials showed similar inhibition levels (~39%) at high concentrations of αFXIIa (20 μg/mL). The presence of prekallikrein in the activation system increased the amount of FXIIa produced during FXII contact activation, and also suppressed the apparent levels of inhibitors on hydrophilic surfaces, while having no effect on apparent levels of inhibitors on hydrophobic surface. The combination of FXII contact activation products and activator surfaces was found to dramatically increase inhibition of αFXIIa activity compared to the activation products alone, regardless of activator surface wettability and the presence of prekallikrein. This finding of inhibitors in the suite of proteins generated by contact activation provides additional knowledge into the complex series of interactions that occur when plasma comes into contact with material surfaces.
Internal surface modification of additively manufactured macroporous TiAl6V4 biomimetic implants via a calciothermic reaction‐based process and osteogenic in vivo responses
Authors: Berger Michael B. , Cohen D. Joshua , Deng Jingyao , Srivas Pavan , Boyan Barbara D. , Sandhage Kenneth H. , Schwartz Zvi
Published: September 2023

Three‐dimensional macroporous titanium–aluminum–vanadium (TiAl6V4) implants produced by additive manufacturing (AM) can be grit blasted (GB) to yield microtextured exterior surfaces, with additional micro/nano‐scale surface features provided by subsequent acid etching (AE). However, the line‐of‐sight nature of GB causes the topography of exterior GB + AE‐modified surfaces to differ from internal GB‐inaccessible surfaces. Previous in vitro studies using dense TiAl6V4 substrates indicated that a nonline‐of‐sight, calciothermic‐reaction (CaR)‐based process provided homogeneous osteogenic nanotextures on GB + AE surfaces, suggesting it could be used to achieve a homogeneous nanotopography on external and internal surfaces of macroporous AM constructs. Macroporous TiAl6V4 (3D) constructs were produced by direct laser melting and modified by GB + AE, with the CaR process then applied to 50% of constructs (3DCaR). The CaR process yielded nanoporous/nanorough internal surfaces throughout the macroporous constructs. Skeletally mature, male Sprague–Dawley rats were implanted with these constructs using a cranial on‐lay model. Prior to implantation, a Cu++‐free click hydrogel was applied to half of the constructs (3D + H, 3DCaR + H) to act as a challenge to osseointegration. Osseointegration was compared between the four implant groups (3D, 3DCaR, 3D + H, 3DCaR + H) at 4w. 3D + H implants exhibited lower bone volume (BV) and percent bone ingrowth (%BI) than the 3D implants. In contrast, osseointegrated 3DCaR + H implants had similar BV and %BI as the 3DCaR implants. Implant pull‐off forces correlated with these results. In vitro analyses indicated that human bone marrow stromal cells (MSCs) exhibited enhanced production of osteoblast differentiation markers and factors associated with osteogenesis when grown on CaR‐modified 3D substrates relative to control (TCPS) substrates. This work confirms that the CaR process provides osteogenic nanotextures on internal surfaces of macroporous 3D implants, and suggests that CaR‐modified surfaces can promote osseointegration in cases where osteogenesis is impaired.
Toward accurate modeling of structure and energetics of bulk hexagonal boron nitride
Authors: Novotný Michal , Dubecký Matúš , Karlický František
Published: September 2023

Materials that exhibit both strong covalent and weak van der Waals interactions pose a considerable challenge to many computational methods, such as DFT. This makes assessing the accuracy of calculated properties, such as exfoliation energies in layered materials like hexagonal boron nitride (h‐BN) problematic, when experimental data are not available. In this paper, we investigate the accuracy of equilibrium lattice constants and exfoliation energy calculation for various DFT‐based computational approaches in bulk h‐BN. We contrast these results with available experiments and reference fixed‐node diffusion quantum Monte Carlo (QMC) results. From our reference QMC calculation, we obtained an exfoliation energy of 2 meV/atom (‐0.380.02 J/m).
Assessment of monocytic‐myeloid‐derived suppressive cells (M‐MDSC) before and after allogeneic hematopoietic stem cell transplantation in acute leukemia patients
Authors: Peterlin Pierre , Béné Marie C. , Jullien Maxime , Guillaume Thierry , Bourgeois Amandine Le , Garnier Alice , Debord Camille , Eveillard Marion , Chevallier Patrice
Published: September 2023

In this monocentric prospective study, the influence on long‐term outcomes of peripheral blood levels of monocytic‐myeloid‐derived suppressive cells (M‐MDSC) was investigated in 56 patients with acute leukemia (myeloid n = 47; lymphoid n = 9) before and after (Days+60/+90) allogeneic hematopoietic stem cell transplantation (Allo‐HSCT). A risk of relapse was found to be associated with a level of pregraft M‐MDSC above 1.4% by ROC curve analysis. In multivariate analysis, this threshold retained a strong statistical significance (HR: 5.94 [2.09–16.87], p = 0.001). Considering only the group of patients who were in complete remission prior to Allo‐HSCT (n = 44), a significant prediction of relapse was found to be associated, in multivariate analysis, with a level of pregraft M‐MDSC above 1.4% (HR: 55.01 [14.95–202.37], p < 0.001) together with pregraft‐positive measurable ‐residual disease (MRD) (HR: 11.04 [1.89–64.67], p = 0.008). A poorer OS (HR: 6.05 [1.24–29.59], p = 0.026) and disease‐free survival (HR: 6.52 [1.41–30.19], p = 0.016) were also associated with higher levels of pregraft M‐MDSC. Remarkably, no relapse occurred in patients with pregraft‐negative MRD and ≤1.4% of M‐MDSC (vs. a 3‐year relapse rate of 60% for others, p = 0.004). Patients developing grade 3–4 acute graft‐versus‐host‐disease (GVHD, median occurrence: day+30 posttransplant) showed significantly higher levels of M‐MDSC% at days +60 and +90, suggesting a possible amplification of these immunosuppressive cells as a reaction to GVHD. In conclusion, this prospective study demonstrates a negative impact of higher proportions of peripheral M‐MDSC before Allo‐HSCT in leukemic patients. This paves the way to potential therapeutic intervention to decrease M‐MDSC levels before Allo‐HSCT and thus perhaps the incidence of relapse in such patients.
Facile synthesis and anticancer activity of tetrazolyl‐benzothiazole derivatives
Authors: Hsu Yu‐Ju , Shi Wei‐Xin , Tseng Yin‐Chen , Chiu Tzu‐Hao , Cheng Ming‐Hsiang , Chen Kuo‐Ting
Published: September 2023

We herein reported a concise synthesis of a new class of tetrazolyl‐benzothiazoles (TBTs). This synthesis was achieved via a microwave‐assisted ANRORC method followed by an acid‐catalyzed [2 + 3] cycloaddition. The TBT core was elaborated with diverse substituents at the N‐1 or N‐2 position on the tetrazole ring to create a compound library for further bioactivity evaluation. The newly synthesized TBT‐based compounds were assessed for their inhibitory effects against human breast cancer cell lines, MCF‐7 and MDA‐MB‐231. Our results revealed that N‐2 substituted TBTs were generally more active than their N‐1 isomers, and 11g emerged as the most potent inhibitor with IC50 values of 5.3 and 10.4 μg/mL against MCF‐7 and MDA‐MB‐231, respectively. This study provides new insights into the synthesis and anticancer inhibitory activity of TBTs, highlighting their potential for future drug development.