bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical criteria for limbic‐predominant age‐related TDP‐43 encephalopathy
Authors: Wolk David A. , Nelson Peter T. , Apostolova Liana , Arfanakis Konstantinos , Boyle Patricia A. , Carlsson Cynthia M. , Corriveau‐Lecavalier Nick , Dacks Penny , Dickerson Bradford C. , Domoto‐Reilly Kimiko , Dugger Brittany N. , Edelmayer Rebecca , Fardo David W. , Grothe Michel J. , Hohman Timothy J. , Irwin David J. , Jicha Gregory A. , Jones David T. , Kawas Claudia H. , Lee Edward B. , Lincoln Karen , Maestre Gladys E. , Mormino Elizabeth C. , Onyike Chiadi U. , Petersen Ronald C. , Rabinovici Gil D. , Rademakers Rosa , Raman Rema , Rascovsky Katya , Rissman Robert A. , Rogalski Emily , Scheltens Philip , Sperling Reisa A. , Yang Hyun‐Sik , Yu Lei , Zetterberg Henrik , Schneider Julie A.
Published: January 2025

Limbic predominant age‐related TDP‐43 encephalopathy neuropathologic change (LATE‐NC) is highly prevalent in late life and a common co‐pathology with Alzheimer's disease neuropathologic change (ADNC). LATE‐NC is a slowly progressive, amnestic clinical syndrome. Alternatively, when present with ADNC, LATE‐NC is associated with a more rapid course. With the emergence of anti‐amyloid therapeutics, discrimination of LATE‐NC from ADNC is critical and will lead to greater clinical recognition of amnestic patients without ADNC. Furthermore, co‐pathology with LATE‐NC may influence outcomes of these therapeutics. Thus there is a need to identify patients during life with likely LATE‐NC. We propose criteria for clinical diagnosis of LATE as an initial framework for further validation. In the context of progressive memory loss and substantial hippocampal atrophy, criteria are laid out for probable (amyloid negative) or possible LATE (amyloid biomarkers are unavailable or when amyloid is present, but hippocampal neurodegeneration is out of proportion to expected pure ADNC).

Highlights

Limbic‐predominant age‐related TDP‐43 encephalopathy (LATE) is a highly prevalent driver of neuropathologic memory loss in late life.

LATE neuropathologic change (LATE‐NC) is a common co‐pathology with Alzheimer's disease neuropathologic change (ADNC) and may influence outcomes with emerging disease‐modifying medicines.

We provide initial clinical criteria for diagnosing LATE during life either when LATE‐NC is the likely primary driver of symptoms or when observed in conjunction with AD.

Definitions of possible and probable LATE are provided.
Rhodium‐mediated Assembly of New Heterocycles: From Borylenes to Oxaboroles
Authors: Hsiang Shou‐Jen , Hayes Paul G.
Published: January 2025

Base‐stabilized rhodium borylene complex κ2‐L(CO)Rh(BMes), 2; κ2‐L=κ2‐NN’‐Rh,κ1‐N−B‐(2,5‐[iPr2P=N(4‐iPrC6H4)]2‐N’(C4H2)−); Mes=mesityl, reacts with a series of alkynes (PhC≡C—R; R=Ph, Me, CO2Et, H) to yield unique structures whereby the alkyne has regioselectively added across boron and the carbon atom of a CO ligand. The resulting complexes, LRh[C(O)C(Ph)C(R)B(Mes)], 3R, react with additional CO to afford cycle‐containing products, L(CO)Rh
), 5R, that ultimately release highly functionalized organic heterocycles of the form
=NPipp (Pipp=4‐iPrC6H4), 6. These oxaboroles, which were assembled from a primary hydroborane, CO, an alkyne, and an azide‐generated NPipp, are structurally analogous to two of the five boron‐containing therapeutics approved by the FDA.
Two‐Level Spatially Localized Proximity Labeling for Cross‐Biological‐Hierarchy Measurement and Manipulation
Authors: Chen Liusheng , Li Yiran , Guo Yuna , Wang Guyu , Feng Nan , Sun Jiahui , Zhong Yihong , Yao Yunyan , Ding Lin , Ju Huangxian
Published: January 2025

Proximity labeling (PL) has emerged as a powerful technique for the in situ elucidation of biomolecular interaction networks. However, PL methods generally rely on single‐biological‐hierarchy control of spatial localization at the labeling site, which limits their application in multi‐tiered biological systems. Here, we introduced another enzymatic reaction upstream of an enzyme‐based PL reaction and targeted the two enzymes to markers indicating different biological hierarchies, establishing a two‐level spatially localized proximity labeling (P2L) platform for in situ molecular measurement and manipulation. Using the cellular‐ and glycan‐level as the hierarchical models, we demonstrated the ability of P2L to efficiently execute a two‐step logic operation and to discriminate target cells with different levels of glycosylation within mixed cell populations. By mounting clickable handles via P2L, we reprogrammed the robust covalent assembly of cells at designated sites. The combination of P2L with proteomics led to the profiling of the protein microenvironment of specific glycans on target cells, revealing changes in tumor‐cell‐surface interactions under immune pressure from a glycan perspective. P2L provides not only a solution for revealing the heterogeneity of biological systems, but also new insights in the fields of intelligent logic computation, enzyme engineering, tissue engineering, etc.
Advances in the Design of Photoactivatable Metallodrugs: Excited State Metallomics
Authors: Shi Huayun , Marchi Rafael C. , Sadler Peter J.
Published: January 2025

Photoactivatable metal complexes offer the prospect of novel drugs with low side effects and new mechanisms of action to combat resistance to current therapy. We highlight recent progress in the design of platinum, ruthenium, iridium, gold and other transition metal complexes, especially for applications as anticancer and anti‐infective agents. In particular, understanding excited state chemistry related to identification of the bioactive species (excited state metallomics/pharmacophores) is important. Photoactivatable metallodrugs are classified here as photocatalysts, photorelease agents and ligand‐activated agents. Their activation wavelengths, cellular mechanisms of action, experimental and theoretical metallomics of excited states and photoproducts are discussed to explore new strategies for the design and investigation of photoactivatable metallodrugs. These photoactivatable metallodrugs have potential in clinical applications of Photodynamic Therapy (PDT), Photoactivated Chemotherapy (PACT) and Photothermal Therapy (PTT).
Kinetic Control of Self‐Assembly Pathway in Dual Dynamic Covalent Polymeric Systems
Authors: Liu Ling , Deng Yuanxin , Qu Da‐Hui , Feringa Ben L. , Tian He , Zhang Qi
Published: January 2025

Kinetically controlled self‐assembly is garnering increasing interest in the field of supramolecular polymers and materials, yet examples involving dynamic covalent exchange remain relatively unexplored. Here we report an unexpected dynamic covalent polymeric system whose aqueous self‐assembly pathway is strongly influenced by the kinetics of evaporation of water. The key design is to integrate dual dynamic covalent bonds—including disulfide bonds and boroxine/borate—into a dynamic equilibrium system of monomers, polymers, and materials. This dual dynamic covalent design allows polymer growth and crosslinking to occur with the same spatiotemporal characteristics, governed solely by solvent evaporation. We found that a single building block can assemble into two distinct types of polymeric materials, each characterized by unique crosslinking topologies, orders, solubility, and macroscopic properties. The dual dynamic nature of the materials imparts them with intrinsic reconfigurability, such as interfacial repairability and close‐loop chemical recyclability.
Organocatalytic [4+2] Benzannulation Between 1,4‐Dithiane‐Based Enal and Nitroolefins to Access 2‐Nitrobiaryls
Authors: Shah Imtiyaz Ahmad , Nagare Yadav Kacharu , Rangan Krishnan , Iype Eldhose , Sharma Ruchika , Kant Rajni , Kumar Indresh
Published: January 2025

A simple method for constructing unsymmetrical 2‐nitrobiaryls has been developed between substituted 1,4‐dithiine‐2‐carbaldehyde and nitroolefins under metal‐free conditions. To gain the advantage of the HOMO‐raising effect of temporary substitutions on in situ generated dienamine intermediate, the present protocol established [4+2] benzannulation of 1,4‐dithiane‐tethered enals with nitroolefin. Further, easy unmasking of 1,4‐dithiine units results in a benzannulation product like that of unsubstituted enals, which are difficult to access. Several 2‐nitrobiaryls have been accessed with moderate to good yields and with promising synthetic applications.
A New Fluorescence Probe for the Quantification of Acetylcysteine and Carbocisteine in Bulk and Spiked Urine: Greenness Appraisal by Exploiting Different GAC‐Metric Strategies
Authors: Elbardisy Hadil M. , Belal Tarek S. , El‐Tahawy Mohsen M. T. , Talaat Wael , Keshk Reda M.
Published: January 2025

Herein, a novel spectrofluorometric sensor is proposed for the sensitive analysis of two nonfluorescent mucolytic drugs, namely, acetylcysteine (ACT) and carbocisteine (CST), utilizing the newly synthesized 2‐[(2‐hydroxyethyl)‐(2,8,10‐trimethylpyrido[2′,3′:3,4]pyrazolo[1,5‐a]pyrimidin‐4‐yl)‐amino]‐ethanol as a fluorescence probe (Flu. Probe). This fluorophore exhibits fluorescence emission at 445 nm upon excitation at 275 nm. The addition of increasing concentrations of each drug resulted in quantitative quenching of the Flu. Probe's fluorescence. Investigation into the quenching mechanism revealed that static quenching is the primary contributing factor for both drugs. The spectroscopic characteristics of the Flu. Probe in the presence of ACT and CST were analyzed using DFT and TD‐B3LYP calculations, revealing typical π → π* transitions, attributed to stable hydrogen‐bonding structures. The developed method was validated in accordance with ICH Q2(R1) guidelines. Linear responses for ACT and CST were observed over concentration ranges 0.125–2.25 and 0.125–3.0 μg/mL, respectively, with detection limits (LODs) 31.97 and 37.14 ng/mL. The proposed spectrofluorometric platform was successfully applied to the analysis of ACT and CST in pharmaceutical dosage forms and spiked urine, within concentration ranges 0.25–2.25 and 0.25–2.50 μg/mL and LODs = 80.21 and 71.48 ng/mL, respectively. Finally, the greenness of the proposed protocol was evaluated employing GAPI, hexagon, and AGREE approaches.
Sustainability‐Oriented Leadership and Business Strategy: Examining the Roles of Procedural Environmental Justice and Job Embeddedness
Authors: Iqbal Qaisar , Piwowar‐Sulej Katarzyna , Agarwal Reeti , Yaqub Muhammad Zafar
Published: January 2025

Organizations are progressively focusing on their sustained growth by designing and implementing environmentally friendly policies. However, their environmental performance depends on their employees' proenvironmental behavior and the firm's sustainability policies. Previous research has provided evidence that environmentally specific servant leadership, transformational leadership, ethical leadership, spiritual leadership, and charismatic (value‐based) leadership enhance employee organizational citizenship behavior toward the environment (OCBE). However, limited research examines the role of sustainability‐oriented leadership (SOL) in maturing employees' OCBE. This research examines the SOL–employee OCBE linkage mediated through mechanisms like perceived environmental justice and affective commitment to one's supervisor under varying permutations of employee job embeddedness (EJE). More specifically, this paper examines SOL's direct, indirect, and moderated effects on OCBE through perceived environmental justice and employee commitment toward the leader under disparate EJE levels. The empirical findings confirm a direct impact of SOL on employees' OCBE. It was also evident that SOL significantly and indirectly influences employees' OCBE through procedural environmental justice under disparate levels of job embeddedness. The paper advances academic and managerial understanding on OCBE proliferate in organization. Besides enriching literature, the study's findings provide valuable insights to organizations seeking to enhance OCBE through fostering SOL, PEJ, and EJE.
Comparative Study of Iminodibenzyl and Diphenylamine Derivatives as Hole Transport Materials in Inverted Perovskite Solar Cells
Authors: Caicedo-Reina Mauricio , Rocha-Ortiz Juan S. , Wu Jianchang , Bornschlegl Andreas J. , Leon Salvador , Barabash Anastasia , Perea Jose Dario , Wang Yunuo , Arango-Marín Vanessa , Ortiz Alejandro , Lüer Larry , Hauch Jens A. , Insuasty Braulio , Brabec Christoph J.
Published: January 2025

Perovskite solar cells (PSCs) have recently achieved over 26% power conversion efficiency, challenging the dominance of silicon‐based alternatives. This progress is significantly driven by innovations in hole transport materials (HTMs), which notably influence the efficiency and stability of PSCs. However, conventional organic HTMs like PTAA, although highly efficient, suffer from thermal degradation, moisture ingress, and high cost. This study explores the potential of iminodibenzyl, a moiety known for its strong electron‐donating capabilities in pharmaceutical applications, as a novel HTM. A series of fluorene‐based derivatives incorporating iminodibenzyl (TMF‐2 and TDF‐2) and diphenylamine (TMF‐1 and TDF‐1) units were synthesized and characterized. The new HTMs demonstrated commendable optical, electrochemical, and thermal properties, as well as enhanced photostability. Among them, TDF‐2 achieved a power conversion efficiency (PCE) of 19.38%, the highest of the new materials. Although these efficiencies are slightly lower than the benchmark PTAA (20.20%), the study underscores the potential of iminodibenzyl to enhance photostability and increase HOMO levels, making it a promising candidate for future HTM development in PSCs.
Assessment of two‐phase slug frequency correlations in horizontal pipes under different operational conditions
Authors: Mohmmed Abdalellah O. , Al‐Kayiem Hussain H. , Abdul‐Majeed Ghassan , Al‐Sarkhi Abdelsalam
Published: January 2025

Accurate prediction of the slug frequency in horizontal pipe flow is essential for appropriate design and operation in various industrial processes. This study provides a comprehensive review of existing empirical correlations for slug frequency in horizontal pipes, highlighting their limitations and applicability. A total of 36 correlations were examined, and 1083 data points were collected from experiments using pipes with inner diameters ranging from 3.7 to 150 mm. The correlations were categorized based on pipe diameter and gas–liquid working fluids. The correlations based on the Froude number had the best performance for superficial liquid velocities within the range of vSL = 0.502–1.505 m/s, with a maximum mean relative difference (MRD) of ±30% and a mean absolute relative difference (MARD) of 40% for superficial gas velocities vSG greater than 1 m/s. The Strouhal number produced the most effective correlations for most of the datasets examined in slug frequency testing. In contrast, the air–oil slug frequency correlations were unable to accurately predict the air‐water experimental data, except for that of Al‐Safran (2016), which was limited to small‐diameter pipes. 909 data points were used to evaluate slug frequency for high viscous fluids; the results showed that the correlation of Baba et al. (2017) provided the best prediction performance, with a maximum MRD of 30%.
Research on the adsorption capacity and mechanism of carbon dioxide by ion exchange resin loaded with metal–organic cages
Authors: Wang Huaheng , Liu Xinmin , Zhang Qingrui , Guo Qingjie
Published: January 2025

Metal–organic cages (MOCs), a novel type of porous material, have shown great potential in the adsorption and separation of CO2 gas. Zirconium‐based metal–organic cages (Zr‐MOCs) have garnered special attention because of their outstanding stability and high solubility. Nevertheless, due to its powdery nature and the tendency for easy aggregation, its application in the industrial field is limited. Here, drawing inspiration from water treatment, the inexpensive and stable ionic exchange resin D001 was employed as the supporting material for loading Zr‐MOCs, and D001‐Zr‐MOC was prepared. The adsorption capacity of D001‐Zr‐MOC for CO2 from the mixed gas (15% CO2/85% N2) under diverse loads of Zr‐MOCs, various temperatures, and different gas flow rates was investigated, and its cyclic adsorption performance for CO2 was determined. The adsorption mechanism of CO2 on D001‐Zr‐MOC was probed by means of adsorption energy, adsorption isotherm, adsorption heat, and diffusion coefficient. The results showed that the maximum CO2 adsorption capacity of D001‐Zr‐MOC was 3.96 mmol/g. The adsorption capacity decreased by merely 4.62% after 10 adsorption/desorption cycles. The adsorption energy and adsorption heat of D001‐Zr‐MOC for CO2 molecules are relatively high, which indicates that D001‐Zr‐MOC has good adsorption capacity and selectivity for CO2 molecules. The adsorption of CO2 is regarded as a typical Langmuir monolayer adsorption, and it is verified that a chemical reaction occurred between CO2 and the adsorbent. CO2 possesses a higher diffusion coefficient, and the excellent cyclic adsorption capacity of D001‐Zr‐MOC is verified.
Protonation effects in protein‐ligand complexes ‐ a case study of endothiapepsin and pepstatin A with computational and experimental methods
Authors: Czodrowski Paul , Vatheuer Helge , Palomino-Hernandez Oscar , Müller Janis , Galonska Phillip , Glinca Serghei
Published: January 2025

Protonation states serve as an essential molecular recognition motif for biological processes. Their correct consideration is key to successful drug design campaigns, since chemoinformatic tools usually deal with default protonation states of ligands and proteins and miss atypical protonation states. The protonation pattern for the Endothiapepsin/PepstatinA (EP/pepA) complex is investigated using different dry lab and wet lab techniques. ITC experiments revealed an uptake of more than one mole of protons upon pepA binding to EP. Since these experiments were performed at physiological conditions (and not at pH=4 at which a large variety of crystal structures is available), a novel crystal structure at pH=7.6 was determined. This crystal structure showed that only modest structural changes occur upon increasing the pH value. This lead to computational studies (Poisson Boltzmann calculations and constant pH MD simulations) to reveal the exact location of the protonation event. Both computational studies could reveal a significant pKa shift resulting in non‐default protonation state and that the catalytic dyad is responsible for the uptake of protons. This study shows that assessing protonation states for two separate systems (protein and ligand) might result in the incorrect assignment of protonation states and hence incorrect calculation of binding energy.
Comparison of the Efficacy and Safety of PD‐1/PD‐L1 Inhibitors in the Treatment of Small Cell Lung Cancer
Authors: Zhang Qichen , Han Xiaojuan , Liu Jiayi , Qiao Hui
Published: January 2025

Objective

This study aims to evaluate the efficacy and safety of PD‐1/PD‐L1 inhibitors in treating small‐cell lung cancer (SCLC) and determine the role of PD‐1 monoclonal antibodies in improving patient outcomes.

Methods

A retrospective analysis was performed on 37 SCLC patients who received PD‐1 or PD‐L1 inhibitors along with chemotherapy at the First Hospital of Lanzhou University between June 2018 and June 2023. Treatment effectiveness was measured by overall response rate (ORR), disease control rate (DCR), overall survival (OS), and progression‐free survival (PFS), utilizing chi‐square and T‐tests, along with Kaplan–Meier and log‐rank analyses.

Results

In the PD‐L1 group, 16 patients achieved partial or complete response, versus 12 in the PD‐1 group, though the difference in the ORR was not statistically significant (50.0% vs. 36.8%, p = 0.308). Median survival times were 21.0 months for PD‐L1 and 17.0 months for PD‐1, with no statistically meaningful difference (p = 0.180). Adverse effects were comparable between the groups in terms of thyroid function (p = 0.898), but bone marrow suppression and gastrointestinal reactions were significantly less severe in the PD‐L1 group (p = 0.047 and p = 0.002).

Conclusion

Immunotherapy combined with chemotherapy offers significant benefits for advanced SCLC patients, irrespective of the type of inhibitor used. Despite the higher incidence of adverse reactions with PD‐1 inhibitors, they remain a viable option, particularly when PD‐L1 inhibitors are not available, due to their manageable safety profile and effective response.
Assessment of Treatment Outcomes and Associated Factors Among Pediatric Patients With Burkitt Lymphoma at Kenyatta National Hospital
Authors: Toor Divya Kumari , Degu Amsalu , Karimi Peter N.
Published: January 2025

Background

In developing countries, the treatment outcomes of Burkitt lymphoma are poor due to the poorly equipped healthcare systems. In addition, there is limited comprehensive data within the African continent, including Kenya, about the outcomes of treatment for this cancer.

Aims

To assess treatment outcomes and variables associated with an increased risk of death from disease progression or treatment‐related toxicities among Burkitt lymphoma pediatric patients at the Kenyatta National Hospital (KNH).

Methods and Results

A retrospective one‐arm cohort study was conducted to examine the treatment outcomes of pediatric patients with Burkitt lymphoma. All eligible Burkitt lymphoma pediatric patients treated between January 1, 2016 and December 31, 2022 were included. The patients were retrospectively monitored from the initial cancer diagnosis until either death or the last follow‐up appointment visit in the facility. Data analysis of factors associated with treatment and disease progression‐related death was carried out using the SPSS version 29.0 software. Kaplan–Meier survival and Cox regression analyses were employed to determine the survival time and predictors of mortality, respectively. The median age of the patients at diagnosis was 6 years (range: 3–13 years). The majority of patients were diagnosed with Stage IV disease accounting for 46.7% of all patients. Of the 75 patients studied, 24% (18) of them were died. The 5‐year overall survival rate was 70%, and most patients had stable disease during the follow‐up period. Patients with Stage IV disease who were treated with full‐fuse chemotherapy were 19.2 (AHR = 19.2, 95% CI = 5.2–48.5, p < 0.001) and 7.4 times (AHR = 7.4, 95% CI = 2.2–19.9, p = 0.003) more hazard of dying as compared to patients without metastasis and received a combination of radiation and reduced‐dose chemotherapy, respectively. However, the age, gender, stage of cancer, histological type of cancer, and co‐morbidity were not significant predictors of survival. Because of the retrospective nature of the study design, the data accuracy relied on the proper documentation of medical records in the study setting.

Conclusion

The 5‐year overall survival rate among pediatric burkitt's lymphoma patients was above average as compared to other African countries. Most patients had reduced tumor size and stable disease during the follow‐up period. Metastases and full‐fuse chemotherapy were significant predictors of mortality.
Prolonged Remission in Metastatic Ano‐Rectal Malignant Melanoma With Single Agent Temozolomide
Authors: Swamy Anusha Mruthyunjaya , Sundriyal Deepak , Kapoor Mayank , Khanna Mridul , Phulware Ravi Hari , Jandrasupalli Kranthi Kumar , Shriwastav Ujjawal , Sehrawat Amit
Published: January 2025

Introduction

With the use of immune checkpoint inhibitors (ICIs) and targeted therapies, the clinical outcomes of metastatic melanoma have drastically improved. The current scenario has reduced the use of chemotherapy as a first‐line treatment. We report an interesting case of a patient with stage IV ano‐rectal canal malignant melanoma with an exceptional response to single‐agent temozolomide.

Case Report

We diagnosed a 55‐year‐old female with stage IV anorectal melanoma, BRAF V600 mutation negative. Owing to her poor performance status (PS) and non‐affordability of immunotherapy, after informed decision‐making, she was started on single agent, temozolomide. She achieved a complete metabolic response and sustained it for 3 years and continues to do so with the first‐line single‐agent temozolomide.

Conclusion

In a resource‐limited setting, where access to ICIs and targeted therapies is not feasible, and in patients who fail to tolerate these therapies, oral chemotherapy continues to remain effective and is worth trying in patients with poor PS.
Unveiling Intramolecular [3+2] Cycloaddition Reactions Leading to Functionalized Heterocycles in the Light of Molecular Electron Density Theory
Authors: Mondal Bhaskar , Domingo Luis R , Mohammad‐Salim Haydar A. , Acharjee Nivedita
Published: January 2025

The relative reactivity and cis/trans selectivity of the intramolecular [3+2] cycloaddition (IM32CA) reactions of nitrile oxide (NO), azide (AZ), nitrile sulfide (NS) and nitrile ylide (NY), leading to functionalized heterocycles are studied within the Molecular Electron Density Theory. The kinetically controlled IM32CA reactions are predicted to be cis stereospecific, while the reaction feasibility follows the order NY>NS>NO>AZ with the respective activation Gibbs free energies of 13.7, 17.8, 21.1 and 27.3 kcal ⋅ mol−1 in benzene at 353 K. The decreased activation energy of NY could be correlated with its carbenoid character, relative to the zwitterionic one predicted for the other three species. The AZ reaction showed relatively higher activation parameter, and accordingly higher than that of the NO one, in conformity with the experimental outcomes. Topological analysis of the electronic structure of the transition state structure shows that the formation of the new single bonds has not yet started on any of them according to a non‐concerted mechanism. Analysis of the kinetic parameters of the intermolecular [3+2] cycloaddition reactions of NOs and AZs shows that the low activation entropies associated with the intramolecular processes are the factor responsible for the feasibility of these non‐polar zw‐type IM32CA reactions.
Navigating the Challenges of Cyclosporine as an Alternative to Rifampicin as an OATP1B Index Inhibitor
Authors: Varma Manthena V. S. , Vourvahis Manoli
Published: January 2025

Rifampicin is a widely employed index inhibitor to assess the impact of organic anion transporting polypeptide 1B (OATP1B) inhibition on investigational drugs. The observation of nitrosamines in certain drug products, including rifampicin, has impacted the conduct of clinical drug–drug interaction (DDI) studies with rifampicin drug products. Cyclosporine is a recommended alternative to assess in vivo OATP1B activity; however, challenges exist in its use due to pharmacokinetic (PK) variability and non‐selective inhibition of other drug disposition mechanisms.
Glycerol‐Derived Water‐Lean Amines for Post‐Combustion CO2 Capture: The Improvement in Capacity and Viscosity
Authors: Liu An‐Hua , Zheng Yu‐Jie , Ren Bai‐Hao , Bi Lin‐Zhu , Zhang Ling , Nuermuhamaiti Ayixuwake , Lu Xiao‐Bing
Published: January 2025

Water‐lean absorbents are regarded as a new generation of post‐combustion CO2 capture technology that could significantly relieve those drawbacks posed by traditional aqueous alkanolamines. However, the exponential increase in viscosity during CO2 absorption remains an urgent issue that needs to be resolved before their practical deployment. In this work, novel water‐lean amines based on biomass glycerol have been devised as single‐component CO2 absorbents with low viscosity (79~110 cP at 25 
, 29~39 cP at 40 
) under high capacity (12~18 wt % at 25 
, 10~17 wt % at 40 
). The captured CO2 could be smoothly released by thermal desorption. Results from preliminary stability test and 10 absorption‐desorption cycles showed that such non‐aqueous absorbents had significant structural toughness as well as reusability. Spectroscopic measurements including 13C NMR and in situ FTIR were performed to gain mechanistic insights by monitoring the entire CO2 absorption and desorption process, while DSC, VLE and DFT calculations provided rational interpretation for reaction kinetics and thermodynamics. The synergistic promotion of glycerol ether group on both CO2 chemical and physical absorption was also verified under high pressure conditions.
Cosmeceuticals and Other Techniques to Reduce Bruising From Surgical and Cosmetic Procedures
Authors: Yousefian Faraz , Van Alfen Braden , Yadlapati Sujitha , Goldberg David J. , Gold Michael
Published: January 2025

Background

Bruising is the most common adverse event experienced after cosmetic procedures, dermatologic surgeries, and other surgeries. Bruising can cause significant distress to a patient and may be the reason for unnecessary additional office visits.

AIM

This review aims to outline the therapeutic remedies and prevention methods to decrease bruising after cosmetic procedures and other surgeries as described in the literature. A thorough in‐depth understanding of the treatment of bruising can help improve the patient experience.

Methods

A literature search was conducted on PubMed reviewing remedies for bruising postsurgical and cosmetic procedures in the dermatological field.

Results

A broad variety of remedies for reducing and alleviating bruising after a procedure exist. These treatments include cold compression, ReFORM and RePAIR, various lasers, herbal supplements including Arnica Montana, inhance postinjection serum, vitamin K, peroxide, and tranexamic acid. Results are varied but do show there are treatment options to alleviate bruising.

Conclusions

Physicians performing dermatologic procedures, cosmetic injections, or other surgeries should be aware of the causes and supported remedies for bruising. By understanding the many options out there to decrease bruising, providers can help alleviate the distress that it often causes patients.
Rhodium‐Catalyzed Enantioselective 1,4‐Addition of Arylboronic Acids to 2,3‐Dihydro‐4‐pyridones Using 4,8‐Substituted Bicyclo[3.3.1]nona‐2,6‐dienes as Ligands
Authors: Stončius Sigitas , Sadzevičienė Rita , Labanauskas Linas
Published: January 2025

C2‐symmetric 4,8‐substituted bicyclo[3.3.1]nona‐2,6‐dienes are efficient bidentate steering ligands for the rhodium‐catalyzed asymmetric conjugate addition of arylboronic acids to N‐Cbz‐2,3‐dihydro‐4‐pyridone. The arylation reactions proceed under mild conditions to provide corresponding 2‐aryl‐4‐piperidones in high yields along with excellent enantioselectivities (up to 99.8:0.2 er).
Development of a Core Outcome Set of Domains to Evaluate Acute Pain Treatment After Lumbar Spine Surgery: A Modified Delphi Study
Authors: van de Wijgert Ilse H. , Vissers Kris C. P. , Fenten Maaike G. E. , Rood Akkie , van Boekel Regina L. M. , van Hooff Miranda L.
Published: January 2025

Background

After lumbar spine surgery, a Core Outcome Set (COS) for acute pain is essential to ensure that the most meaningful outcomes are monitored consistently in the perioperative period. The aim of the present study was to consent on a COS for assessing the efficacy of acute pain management for patients undergoing lumbar spinal surgery.

Method

A modified Delphi procedure was conducted among a national (Dutch) expert panel. External endorsement of the final COS was conducted among an international panel of anaesthesiologists and the Dutch chronic pain patient association.

Results

A panel of 35 experts representing 10 stakeholder groups, including orthopaedic surgeons, anaesthesiologists, patient representatives, physician assistants, researchers, a neurosurgeon, nurses, and a psychologist, took part in the Delphi procedure. Five outcome domains reached consensus for inclusion in this COS. This COS contains the following domains: pain intensity, analgesic use, early mobilisation, length of stay, and adverse events. Of an international panel of 27 key opinion leaders, 77% agreed on the final COS. The patient association also consented to the final COS.

Conclusions

A COS to evaluate acute pain treatment after lumbar surgery is proposed after national Delphi consensus rounds and (international) external endorsement. Future research should focus on determining suitable measurement instruments, assessing feasibility, validation, and implementation of the COS in daily clinical practice and research.

Significance

This research proposes a clinically relevant spine‐specific core outcome set (COS) of domains focusing on the acute postoperative phase (until 30 days). This is the first COS for evaluation of acute pain after lumbar spine surgery.
Optimize the Synthesis Error in an Eight‐Bar Peaucellier–Lipkin Mechanism Using an Objective Function Maximization Approach and Application to Load Lifting
Authors: Bodie Nguemiengo Abdel Axis , MBA MBA Frédéric , Epee Alban Fabrice Lionel , Ngayihi Abbe Claude Valery , Kom Charles Hubert
Published: January 2025

This work deals with optimizing the synthesis error in an eight‐bar Peaucellier—Lipkin mechanism, for its dimensional synthesis and applications in load‐lifting machines. A new method for the formulation of the problem of maximizing the objective function is proposed and makes it possible to obtain from the PSO algorithm a minimum synthesis error emin = 9.07E−06 mm for the generation of the straight trajectory when the search interval for the lengths of the bars is [1 mm, 15 mm] and a minimum error emin = 1.47E−04 mm when the search interval is [1000 mm, 15,000 mm]. For 10 simulations in Case 1 the average convergence time is tm = 55 s with the largest iteration at 10 (for t = 159 s); for 100 simulations in Case 2, the tm = 229 s with the largest iteration at 136 (for t = 2294 s). The minimum error of Case 1 is compared with the results of authors in the literature on the generation of the right trajectory because the search space is approximately equal. In the literature, emin = 0.648358 mm with the GA‐DE algorithm in 2010, emin = 2.3667E−005 mm with the MKH algorithm in 2016, emin = 0.027145 mm with the SAP‐TLBO algorithm in 2017, emin = 3.7E−4 with the GA algorithm in 2019. This new method brings a plus, because even when the search space is very large, the algorithm converges quickly and it allows the study to be extended to the generation of circular trajectories by just modifying the ratio between the frame bar and the crank bar. The practical implications of achieving an error as low as 9.07E−06 mm are the design of high‐precision industrial machines with reduced vibration, noise, and premature wear of joints. The results of the post‐design FEM analysis show that for a 1.4571 steel (X6CrNiMoTi17‐12‐2) with a thickness of 50 mm and a joint with a radius of 500 mm, the mechanical device obtained can support a load of 1500 kg.
Predictors of Length of Hospitalization for Neonatal Sepsis at Kenyatta Nation Hospital, Kenya: A Prospective Cross‐Sectional Study
Authors: Tisho Athman Khaltuma , Mbugua Patrick Mwirigi , Bosire Rose , Karanja Simon Muturi
Published: January 2025

Background and Aims

Neonatal sepsis is a major cause of neonatal mortality worldwide. It remains a detrimental bottleneck to the WHO goal of eradicating preventable deaths for children below 5 years of age by 2030. Though the risk factors for adverse clinical outcomes for neonatal sepsis have been widely studied there is no universal consensus. Length of hospitalization is considered an indicator for adverse clinical outcome of neonatal sepsis. Markedly, literature is scarce regarding the drivers of extended hospitalization for neonatal sepsis in Kenya.

Methodology

This study determined the predictors of prolonged hospital stay for neonatal sepsis at the pediatric wards, KNH, Kenya. This was prospective cross‐sectional research carried out among 314 mother/neonate pairs. The neonates were confirmed to have sepsis. Logistic regression analysis was conducted to determine maternal and neonate status predictive of duration of hospitalization.

Results

The median duration of hospital stay was 11 days and the majority (52.9%) were hospitalized for more than 11 days. The findings identified that maternal age ≥ 35 years (OR = 3.72, 95% CI: 1.61–8.59, p = 0.03), UTI during pregnancy (OR = 1.82, 95% CI: 1.07–3.11, p = 0.03), not breastfeeding (OR = 2.31, 95% CI: 1.29–4.14, p = 0.005), convulsion (OR = 2.03, 95% CI: 1.22–3.37, p = 0.01), jaundice (OR = 1.45, 95% CI: 1.10–1.91, p = 0.002), reduced movements (OR = 1.72, 95% CI: 1.08–2.72, p = 0.02), low birthweight (OR = 6.1, 95% CI: 2.48–14.99, p < 0.001) and preterm birth (OR = 3.1, 95% CI: 1.64–5.86, p < 0.001) were significant predictors of longer hospital stay.

Conclusion

The findings provide insights into the factors that can be monitored to predict the prognosis of neonatal sepsis. Besides, remedies can target these variables to mitigate prolonged hospitalization and severity of neonatal sepsis.
Surgical Practice in Resource‐Limited Settings: Perspectives of Medical Students and Early Career Doctors: A Narrative Review
Authors: Achanga BillSmith Anyinkeng , Bisimwa Christian Wabene , Femi‐Lawal Victor Oluwafemi , Akwo Nnoko Sona , Toh Tohson Falake
Published: January 2025

Introduction

Surgical practices in low‐resource countries often fail to meet established standards. Both doctors and medical students have limited exposure to surgical cases, which hinders training and the development of surgical specialization. This study highlights the current state of surgical practice from a trainee's perspective, explores existing gaps in training and capacity building, and recommends practical solutions.

Methods

We conducted a literature search on PubMed, Google Scholar, and other scientific databases using search terms such as “surgical practice,” “doctors' perspectives in surgical practice,” “surgery in low‐ and middle‐income countries,” and “solutions to surgical inadequacy.” We included studies published from 2015 to 2024, with exceptions for a few highly relevant studies published prior to 2015.

Results

We outline the limitations identified in the literature concerning surgical training and healthcare in low‐ and middle‐income countries. Many centers lack adequate infrastructure, human resources, and training. These challenges negatively affect the skills and quality of surgical care. However, some centers demonstrate that surgical practice is feasible through collaboration with institutions established in higher‐income contexts.

Conclusion

Telesurgery, task shifting and sharing, high‐impact, low‐cost surgeries, and collaborations with more developed health systems could effectively bridge the gap in surgical availability in LMICs.
Improving Thermal Performance in Building Heating, Ventilation, and Air Conditioning Systems: A Study of Natural Convection and Entropy in Plus‐Shaped Cavity
Authors: Al‐Badri Alaa R. , Al‐Waaly Ahmed A. Y. , Saha Goutam , Saha Tinni , Saha Suvash C.
Published: January 2025

The impact of building design on energy efficiency has been widely studied, with cavity cooling emerging as an effective solution for indoor thermal comfort, where obstacles within the cavity can enhance fluid flow and improve natural convection heat transfer (HT). This research builds on the principles of cavity cooling for indoor thermal comfort, investigating entropy generation and HT behavior in a unique plus‐shaped cavity containing a cold cylindrical element, analyzed through Computational Fluid Dynamics simulations. The Rayleigh number (Ra) ranges from 103 to 106, with a fixed Prandtl number (Pr) of 0.71, representing air as the working fluid, radius (r) of the cylinder ranges from 0 to 0.1, where r = 0 indicates no cylinder. The results indicate significant shifts in flow structure and temperature distribution across the cavity at varying Ra values, impacting the local and global entropy generation. High Rayleigh numbers lead to enhanced convective flows, intensifying entropy production near the cylinder surface due to steeper thermal gradients and vigorous recirculation zones. The increase in Ra from 103 to 106 leads to an increase in Nuavg from 24.27 to 56.40 for the model without a cold object while from 39.62 to 123.83 for the model with a cold object. Moreover, the maximum enhancement in Nuavg was 137.48% for Ra = 105. Whereas, for the same value of Ra = 105, the maximum increase in Egen and Be was 474.92% and 33.16%, respectively. Also, a new correlation is proposed to calculate Nuavg using response surface methodology. This study offers a comprehensive examination of heat flow characteristics and entropy generation rates in confined geometries, contributing valuable knowledge to thermal management and optimization in systems with internal obstacles.
The Relationship Between Novel Inflammatory Markers and Serum 25‐Hydroxyvitamin D Among US Adults
Authors: Zhao Hang , Zhao Yangyang , Fang Yini , Zhou Weibang , Zhang Wenjing , Peng Jiecheng
Published: January 2025

Background

Vitamin D is the focus of extensive medical research globally. Recent studies have investigated the correlation between serum 25‐hydroxyvitamin D (25(OH)D) and common inflammatory markers. However, few studies have incorporated novel inflammatory markers such as the platelet‐to‐lymphocyte ratio (PLR), platelet‐to‐high density lipoprotein cholesterol ratio (PHR), systemic inflammatory index (SII), neutrophil‐to‐lymphocyte ratio (NLR), systemic inflammatory response (SIRI), and neutrophil‐to‐high‐density lipoprotein cholesterol ratio (NHR). This study investigated these correlations among adults in the USA.

Methods

We ultimately included a total of 5308 participants from the National Health and Nutrition Examination Survey (NHANES) database spanning 2007 to 2018. A multivariable linear regression model assessed the links between serum 25(OH)D and these novel inflammatory markers, with subgroup analyses for hypertension and diabetes. To further explore the relationship between the two, we applied smooth curve fittings and generalized additive models. Upon detecting nonlinear relationships, we used a recursive algorithm to pinpoint the inflection point.

Results

In our multivariate linear regression model, serum 25(OH)D concentrations were negatively correlated with NHR (β = −0.003, 95% CI: −0.005 to −0.001), NLR (β = −0.002, 95% CI: −0.003 to 0.000), SII (β = −0.579, 95% CI: −0.954 to −0.205), PHR (β = −0.171, 95% CI: −0.249 to −0.093), and PLR (β = −0.096, 95% CI: −0.051 to −0.040) among adults in the USA. Nevertheless, no significant association was found with SIRI (β = −0.001, 95% CI: −0.002 to 0.000). Subgroup analysis by hypertension and diabetes showed that in the hypertensive group, serum 25(OH)D was significantly and negatively associated with NHR, NLR, SII, SIRI, PHR, and PLR. However, no correlation was found in the diabetic group between serum 25(OH)D levels and these inflammatory markers.

Conclusions

Our research confirms that serum 25(OH)D levels are negatively correlated with several novel inflammatory markers among adults in the USA, suggesting potential directions for further research into vitamin D's role in inflammation.
Assessment of a Single‐Element Scanning System for Enhanced Photoacoustic Imaging of Brain Hemorrhage
Authors: Benavides Lara Juliana , Prakash Ravi , Avanaki Kamran
Published: January 2025

The use of photoacoustic brain imaging for hemorrhage detection holds significant clinical importance. This study focuses on the performance of sensitivity and detection capabilities of a single‐element scanning system, considering the remarkable signal‐to‐noise ratio of photoacoustic signals generated by a single‐element transducer. By employing blood vessel‐like phantoms and ex vivo brain phantoms, we demonstrated the superior efficacy of the single‐element scanning method over the transducer array system in the context of brain hemorrhage detection. This research highlights the potential for enhancing hemorrhage detection sensitivity through careful design and optimization of the proposed method, thereby increasing its viability for clinical application.
A Streamlined High‐Throughput LC–MS Assay for Quantifying Peptide Degradation in Cell Culture
Authors: Rozans Samuel J. , Wu Yingjie , Moghaddam Abolfazl S. , Pashuck E. Thomas
Published: January 2025

Peptides are widely used in biomaterials due to their ease of synthesis, ability to signal cells, and modify the properties of biomaterials. A key benefit of using peptides is that they are natural substrates for cell‐secreted enzymes, which creates the possibility of utilizing cell‐secreted enzymes for tuning cell–material interactions. However, these enzymes can also induce unwanted degradation of bioactive peptides in biomaterials, or in peptide therapies. Liquid chromatography–mass spectrometry (LC–MS) is a widely used, powerful methodology that can separate complex mixtures of molecules and quantify numerous analytes within a single run. There are several challenges in using LC–MS for the multiplexed quantification of cell‐induced peptide degradation, including the need for nondegradable internal standards and the identification of optimal sample storage conditions. Another problem is that cell culture media and biological samples typically contain both proteins and lipids that can accumulate on chromatography columns and degrade their performance. Removing these constituents can be expensive, time‐consuming, and increases sample variability. However, loading unpurified samples onto the column without removing lipids and proteins will foul the column. Here, we show that directly injecting complex, unpurified samples onto the LC–MS without any purification enables rapid and accurate quantification of peptide concentration and that hundreds of LC–MS runs can be done on a single column without significantly diminishing the ability to quantify the degradation of peptide libraries. To understand how repeated injections degrade column performance, a model library was injected into the LC–MS hundreds of times. It was then determined that column failure is evident when hydrophilic peptides are no longer retained on the column and that failure can be easily identified by using standard peptide mixtures for column benchmarking. In total, this work introduces a simple and effective method for simultaneously quantifying the degradation of dozens of peptides in cell culture. By providing a streamlined and cost‐effective method for the direct quantification of peptide degradation in complex biological samples, this work enables more efficient assessment of peptide stability and functionality, facilitating the development of advanced biomaterials and peptide‐based therapies.
Glucose Transporter 1 Deficiency Impairs Glucose Metabolism and Barrier Induction in Human Induced Pluripotent Stem Cell‐Derived Astrocytes
Authors: Pervaiz Iqra , Mehta Yash , Al‐Ahmad Abraham Jacob
Published: January 2025

Glucose is a major source of energy for the brain. At the blood–brain barrier (BBB), glucose uptake is facilitated by glucose transporter 1 (GLUT1). GLUT1 Deficiency Syndrome (GLUT1DS), a haploinsufficiency affecting SLC2A1, reduces glucose brain uptake. A lot of effort has been made to characterize GLUT1DS at the BBB, but the impact on astrocytes remains unclear. In this study, we investigated the impact of GLUT1DS on astrocyte differentiation and function in vitro, using human induced pluripotent stem cells GLUT1DS (GLUT1DS‐iPSCs) differentiated into astrocyte‐like cells (iAstros). GLUT1 expression is decreased during the differentiation of iPSCs into astrocytes, with neural progenitor cells showing the lowest expression. The presence of a truncated GLUT1 did not compromise the differentiation of iPSCs into iAstros, as these cells could express several key markers representative of the astrocyte lineage. GLUT1DS‐iAstros failed to express full‐length GLUT1 at protein levels while showing no signs of impaired GLUT4 expression. However, GLUT1DS‐iAstros showed decreased glucose uptake and lactate production compared to control‐iAstros, reduced glycolysis, and mitochondrial activity as well as ATP deficit. In addition to reduced energy production, astrocytes displayed a reduced extracellular glutamate release. As previously observed, one iAstros clone (C7) showed the most severe phenotype from all groups. Our study provides an insightful view of the contribution of GLUT1 in astrocytes' energetic metabolism and raises the possible contribution of these cells in the astrocyte–neuron metabolic coupling. Our future direction is to understand better how GLUT1DS impacts astrocytes and neurons within their metabolic coupling.