bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro cancer cell line luminescence‐based validation of anticancer phytocompounds obtained from Leucas biflora against HELA cervical and A549 lung cancer cells
Authors: Chitra Kandasamy , Sureshkumar Muthusamy , Muraleedharan Aiswarya , Selvamaleeswaran Ponnusamy , Selvankumar Thangaswamy , Thirumalaisamy Rathinavel , Alyami Nouf M. , Alharbi Sulaiman Ali
Published: August 2024

Current research aims to screen the anticancer prospective of Leucas biflora phytocompounds against apoptotic regulator target protein essential for cancer progression. In gas chromatography–mass spectrometry analysis major phytocompounds such as tetracosahexaene, squalene, phytol, 22‐stigmasten‐3‐one, stigmasterol, fluorene, and 1,4‐dihydro were identified in ethanolic leaf extract of Leucas biflora. In vitro, the free radical scavenging potential of ethanolic leaf extract of Leucas biflora was examined through its DPPH and ABTS radical scavenging potential IC50 value 15.35 and 13.20 μg/ml, respectively. Dose‐dependent cytotoxicity was monitored against both A549 lung cancer and HELA cervical cancer cells. Leucas biflora ethanolic leaf extract highly reduces the cell viability of both HELA and A549 cells in in vitro cytotoxicity assays. Leucas biflora ethanolic extract produces 23.76% and 29.76% viability rates against A549 lung and HELA cervical cancer cell lines, and their IC50 values differ slightly at 95.80 and 90.40 μg/ml, respectively. In molecular docking analysis lung cancer target protein–ligand complex 5Y9T‐16132746 showed a maximum score of −14 kcal/mol by exhibiting stable binding affinity and interactions among all screened complexes. Based on docking score nine phytocompounds from Leucas biflora and two reference standard drugs were chosen for further analysis. Further validation reveals that the fluorene, 1,4‐dihydro possess good ADMET, Bioactivity and density functional theory indices.
Do auditory brainstem implants favor the development of sensory integration and cognitive functions?
Authors: BAŞ Banu , Gökay Nuriye Yıldırım , Aydoğan Zehra , Yücel Esra
Published: August 2024

Background

Information about the development of cognitive skills and the effect of sensory integration in children using auditory brainstem implants (ABIs) is still limited.

Objective

This study primarily aims to investigate the relationship between sensory processing skills and attention and memory abilities in children with ABI, and secondarily aims to examine the effects of implant duration on sensory processing and cognitive skills in these children.

Methods

The study included 25 children between the ages of 6 and 10 years (mean age: 14 girls and 11 boys) with inner ear and/or auditory nerve anomalies using auditory brainstem implants. Visual‐Aural Digit Span Test B, Marking Test, Dunn Sensory Profile Questionnaire were applied to all children.

Results

The sensory processing skills of children are statistically significant and positive, and moderately related to their cognitive skills. As the duration of implant use increases, better attention and memory performances have been observed (p < .05).

Conclusion

The study demonstrated the positive impact of sensory processing on the development of memory and attention skills in children with ABI. It will contribute to evaluating the effectiveness of attention, memory, and sensory integration skills, and aiding in the development of more effective educational strategies for these children.
Mesenchymal stem cells for osteoarthritis: Recent advances in related cell therapy
Authors: Lin Jianjing , Huang Jingtao , Jiao Zilu , Nian Mengyuan , Li Canfeng , Dai Yali , Jia Shicheng , Zhang Xintao
Published: August 2024

Osteoarthritis (OA) is a degenerative joint disease that affects the entire joint and has been a huge burden on the health care system worldwide. Although traditional therapy and targeted cartilage cell therapy have made significant progress in the treatment of OA and cartilage regeneration, there are still many problems. Mesenchymal stem cells from various tissues are the most studied cell type and have been used in preclinical and clinical studies of OA, because they are more widely available, have a greater capacity for in vitro expansion, and have anti‐inflammatory and immunomodulatory properties compared to autologous chondrocytes. This article will systematically review the latest developments in these areas. It may provide new insights for improving OA and cartilage regeneration.
A comparison of 1‐ versus 3‐month regional anatomy exposure on learning outcomes of undergraduate medical students
Authors: Antipova Veronica , Siwetz Martin , Engelhardt Maren , Fellner Franz A. , Manhal Simone , Niedermair Julian F. , Ondruschka Benjamin , Pietras Sandra M. , Poilliot Amélie J. , Pretterklieber Michael L. , Wimmer‐Röll Monika , Wree Andreas , Hammer Niels
Published: August 2024

Regional anatomy teaching forms a cornerstone of undergraduate medical education. Owing to an increase in teaching and learning content throughout the medical curriculum in recent years, contact hours and overall course durations in anatomy are under review worldwide. This study aimed to assess whether shortening the course content duration impacts learning gain and the ability to identify anatomical structures correctly. Undergraduate medical students of the Johannes Kepler University Linz (JKU;n = 310) and at the Medical University of Graz (MUG;n = 156) participating in regional anatomy courses were included. Whole body regional anatomy courses, including hands‐on dissection and accompanying lectures, were delivered over one or three months. Course content and examination mode were kept consistent, while the duration of knowledge delivery was one or three months, respectively. Objective structured practical examinations (OSPE) were then carried out on prosections for the neck, thorax, and abdomen. 3‐month course exposure resulted in significantly higher OSPE scores for the neck (49 vs. 37%), thorax (65 vs. 54%), and abdomen (65 vs. 45%), respectively. Further evaluation of the utility of different embalming types yielded higher 3‐month scores in the neck and thorax regions with Thiel‐embalmed tissues and thorax and abdomen regions in ethanol‐glycerin‐embalmed tissues. Course exposure over a more extended period, like three months, appears to be highly beneficial.
Prognostic impact of bridge or neoadjuvant induction chemotherapy in patients with resected oral cavity cancer: A nationwide cohort study
Authors: Hsu Cheng‐Lung , Wen Yu‐Wen , Wang Hung‐Ming , Hsieh Chia‐Hsun , Liao Chi‐Ting , Lee Li‐Yu , Ng Shu‐Hang , Lin Chien‐Yu , Chen Wen‐Cheng , Lin Jin‐Ching , Tsai Yao‐Te , Lee Shu‐Ru , Chien Chih‐Yen , Hua Chun‐Hung , Wang Cheng Ping , Chen Tsung‐Ming , Terng Shyuang‐Der , Tsai Chi‐Ying , Fan Kang‐Hsing , Yeh Chih‐Hua , Lin Chih‐Hung , Tsao Chung‐Kan , Cheng Nai‐Ming , Fang Tuan‐Jen , Huang Shiang‐Fu , Kang Chung‐Jan , Lee Li‐Ang , Fang Ku‐Hao , Wang Yu‐Chien , Lin Wan‐Ni , Hsin Li‐Jen , Yen Tzu‐Chen , Liao Chun‐Ta
Published: August 2024

Background

While surgery remains the primary treatment for oral squamous cell carcinoma (OCSCC), induction chemotherapy (IC) can be used as a bridging or neoadjuvant therapy. This nationwide study in Taiwan examines the survival outcomes of OCSCC patients who received IC before surgery.

Methods

We analyzed data from 29,891 patients with OCSCC. Of these, 29,058 initially underwent surgery (OP group), whereas 833 received IC before surgery (IC + OP group). A propensity score (PS)‐matched analysis (4, 1 ratio, 3260 vs. 815 patients) was performed considering tumor subsite, sex, age, Charlson comorbidity index, clinical T1–T4b tumors, clinical N0–3 disease, and clinical stage I–IV.

Results

In the PS‐matched cohort, the 5‐year disease‐specific survival (DSS) and overall survival (OS) rates were 65% and 57%, respectively. When comparing the OP and IC + OP groups, the 5‐year DSS rates were 66% and 62%, respectively (p = 0.1162). Additionally, the 5‐year OS rates were 57% and 56%, respectively (p = 0.9917). No significant intergroup differences in survival were observed for specific subgroups with cT4a tumors, cT4b tumors, cN3 disease, pT4b tumors, and pN3 disease. However, for patients with pT4a tumors, the OP group demonstrated superior 5‐year outcomes compared to the IC + OP group, with a DSS of 62% versus 52% (p = 0.0006) and an OS of 53% versus 44% (p = 0.0060). Notably, patients with cT2–3, cN1, and c‐Stage II disease in the IC + OP group were significantly more likely to achieve pT0–1 status (p < 0.05).

Conclusions

Following PS matching, the IC + OP group generally exhibited similar prognosis to the OP group. However, for pT4a tumors, the OP group showed superior 5‐year outcomes. While IC may not universally improve survival, it could be advantageous for patients who respond positively to the treatment.
Antioxidant and Antibacterial Properties of Ethanolic Pot‐Pollen Extracts of Melipona beecheii and Determination of the Major Components by GC‐MS
Authors: Calderón‐Martínez Patricia , Yam‐Puc Alejandro , Ramón‐Sierra Jesús , Hernández‐Bolio Gloria , Hernández‐Núñez Emanuel , Zamora‐Bustillos Roberto , Ortiz‐Vázquez Elizabeth
Published: August 2024

Melipona beecheii pot‐pollen is a natural product that has barely been studied, unlike other hive products such as honey and propolis. Its application has been reported since ancient times in traditional Mayan medicine, and it is also a functional food with high nutritional value. In the present study, samples of ethanolic pot‐pollen extracts from five locations in the Yucatán Peninsula were analyzed to determine their antibacterial and antioxidant properties. All the extracts showed activity against five medically important bacteria; Pseudomonas aeruginosa and Listeria monocytogenes were the most susceptible bacteria in all samples. The evaluated antioxidant activity was higher than that reported by other studies. Palmitic, linoleic, and linolenic fatty acids and their respective ethyl ethers were detected by Gas Chromatography‐Mass Spectrometry (GC‐MS) in all samples in different concentrations. Based on these results, pot‐pollen extract from Mama, Yucatán exhibited the best biological activities (Minimum Inhibitory Concentrations (MICs) between 6 and 40 mg/mL, EC50 DPPH 28 μg/mL, EC50 RP 30 μg/mL), which could be related to a higher content of unsaturated fatty acids and their ethyl esters. The present study demonstrates that M. beecheii pot‐pollen has therapeutic potential in addition to its benefits as a nutritional supplement.
Prenylated Flavanone Enantiomers with α‐Glucosidase Inhibitory Activity from the Root Bark of Morus alba
Authors: Bi Yan‐Xue , Tian Lin‐Lin , Bao Jie , Zhang Hua
Published: August 2024

A focused chemical investigation into the polar fractions of a well‐known traditional Chinese medicine called Sang‐Bai‐Pi (the root bark of Morus alba) yielded a panel of prenylated flavanones. The new compounds were identified as four pairs of enantiomers (1a/1b–4a/4b) featuring the same constitution structure, on the basis of HRMS, NMR and ECD analyses. Several previously reported known racemic co‐metabolites were also analyzed and separated by HPLC on chiral columns, and the absolute configurations of pure enantiomers were established via ECD technique for the first time. The inhibition of these isolates against the antidiabetic target α‐glycosidase was further tested, with most of them showing decent inhibitory activity compared with the positive control acarbose. The interaction mechanism of two selected compounds (3a & 4b) was explored by kinetics experiment, which revealed a mixed type of inhibition pattern toward the enzyme.
In Vivo Delivery Processes and Development Strategies of Lipid Nanoparticles
Authors: Cheng Jiashun , Jian Lina , Chen Zhaolin , Li Zhuoyuan , Yu Yaobang , Wu Yihang
Published: August 2024

Lipid nanoparticles (LNPs) represent an advanced and highly efficient delivery system for RNA molecules, demonstrating exceptional biocompatibility and remarkable delivery efficiency. This is evidenced by the clinical authorization of three LNP formulations: Patisiran, BNT162b2, and mRNA‐1273. To further maximize the efficacy of RNA‐based therapy, it is imperative to develop more potent LNP delivery systems that can effectively protect inherently unstable and negatively charged RNA molecules from degradation by nucleases, while facilitating their cellular uptake into target cells. Therefore, this review presents feasible strategies commonly employed for the development of efficient LNP delivery systems. The strategies encompass combinatorial chemistry for large‐scale synthesis of ionizable lipids, rational design strategy of ionizable lipids, functional molecules‐derived lipid molecules, the optimization of LNP formulations, and the adjustment of particle size and charge property of LNPs. Prior to introducing these developing strategies, in vivo delivery processes of LNPs, a crucial determinant influencing the clinical translation of LNP formulations, is described to better understand how to develop LNP delivery systems.
Percutaneous transcatheter treatment for partial anomalous pulmonary right venous connection to the superior caval vein without atrial septal defect
Authors: Amici Andrea , Ewert Peter , Elek Miroslav , Georgiev Stanimir
Published: August 2024

We developed technique similar to transcatheter treatment for superior sinus venosus defects to treat a patient with a Partial Anomalous Pulmonary Venous Connection of the right upper pulmonary veins (RUPV) without an atrial septal defect. A double transseptal puncture was performed, and the left atrium (LA) was connected with the RUPV using a covered stent. The blood flow from the superior vena cava was directed to the right atrium (RA) using a second covered stent.
Successful transcatheter aortic valve replacement in a failing HAART 300 aortic valve annuloplasty ring: A case report
Authors: Abdel‐Razek Omar , El Khoury Alessandro , McGrail Daniel , Laham Roger J.
Published: August 2024

Transcutaneous aortic valve replacement (TAVR) has evolved from a complex procedure meant only for patients at prohibitive risk for surgery to a commonly performed procedure across a wide variety of clinical scenarios including the treatment of failed aortic valve bioprosthesis. Annuloplasty rings in the aortic position such as HAART 300 (Biostable Science and Engineering) have been introduced in the management of native aortic regurgitation. Percutaneous management of failed bioprosthesis rings in the aortic position has not been widely described. We present a case of a 69‐year‐old man with recurrent aortic regurgitation successfully treated with TAVR using a SAPIEN 3 valve within a HAART 300 ring.
X‐linked ichthyosis presenting with cryptorchidism for orchidopexy: A rare anesthetic encounter and case report
Authors: Bhatta Sunil , Pandit Sukriti , Chaudhary Pratik , Chhetri Naresh Thapa
Published: August 2024

Key Clinical Message

Cutaneous scaling and associated clinical syndrome displayed in X‐linked ichthyosis mandates multidisciplinary care. Patient with ichthyosis confronts a numerous challenge to an anesthesiologist and demands a rigorous management. As these patients are very vulnerable perioperatively, meticulous care and support are utmost.

Ichthyosis is a group of genetic conditions distinguished by the appearance of hyperkeratotic scales on the skin's surface. X‐linked ichthyosis results from a mutation in the steroid sulfatase (STS) gene, which encodes the steroid sulfatase enzyme. Here we report a case of a 6‐year‐old child with X‐linked ichthyosis. He presented to our operation theater for correction of left‐sided undescended testis and underwent surgery uneventfully. To handle X‐linked ichthyosis perioperatively, meticulous planning and efficient anesthetic administration are critical.
Core myopathy in two siblings with a biallelic variant in the CACNA1S gene—A case series study
Authors: Khoeini Tara , Kariminejad Ariana , Nilipour Yalda , Ariaei Armin , Najmabadi Hossein , Arabshahi Mojtaba , Faraji Zonooz Mehrshid , Haghi Ashtiani Bahram
Published: August 2024

Key Clinical Message

Homozygous variants of Calcium Voltage‐Gated Channel Subunit Alpha1 S (CACNA1S) gene mutation were previously identified as causes of periodic paralysis and congenital early‐onset myopathy, while it could be manifested as a late‐onset congenital core myopathy.

Calcium Voltage‐Gated Channel Subunit Alpha1 S (CACNA1S) gene mutation has been linked to various neuromuscular conditions in recent years. Congenital myopathy with core‐like features is one of the cardinal associations reported previously, causing severe respiratory insufficiency and death in neonates. Informed consent was received from the patients. Subsequently, peripheral blood leukocytes were utilized to extract genomic DNA. Moreover, exome enrichment was implemented through the Twist Human Core Exome Kit (Twist Bioscience) and exome sequenced using Illumina NovaSeq 6000 platform (Illumina, San Diego, CA, USA). Sanger sequencing using BIG Dye Terminators confirmed the presence of the final variant. Finally, the candidate variants were classified based on the American College of Medical Genetics and Genomics (ACMG) guidelines. In this report, we describe two siblings, who presented with childhood and late‐onset progressive muscle weakness, and had a homozygous variant in exon 2 of the CACNA1S gene defined as c.188C > A (p.Ala63Asp) (NM_000069.3). The SIFT, Polyphen2, CADD PHRED, and Mutation Taster analysis tools classified the variant as pathogenic/damaging. The muscle biopsy of the younger brother revealed intermyofibrillar network pattern disruption as cytoplasmic core‐like lesions. The muscle magnetic resonance imaging (MRI) reported grade IIa and IIb fatty changes. Finally, the electromyography (EMG) findings suggested a myopathic change pattern. This report illustrates the clinical variability in CACNA1S‐related myopathy by reviewing prior reports and adding newly found aspects, additionally expanding the gene defects associated with core myopathy.
Antiphospholipid syndrome with major arterial thrombosis, presenting as pulmonary thromboembolism, cerebrovascular accident, and coronary artery disease: A case report and literature review
Authors: Shirani Aria , Daraei Morteza , Shirani Aryan
Published: August 2024

Key Clinical Message

Antiphospholipid syndrome is an immunopathologic disorder that should be considered in all patients with recurrent and/or unexplained thromboembolic events. Antiphospholipid antibodies are diagnostic markers, and anticoagulation therapy is the therapeutic and preventive strategy. Long‐term anticoagulation therapy is necessary, with careful attention to potential bleeding complications.
Pauci‐immune necrotizing glomerulonephritis in a 24‐year‐old female with negative ANCA antibodies: A rare case report
Authors: Hamsho Suaad , Dumirieh Sumaya , Sleiay Mouhammed , AlBaroudi Douha , Alshekh Muhamad Ali , Alahmad Marwa
Published: August 2024

Key Clinical Message

Pauci‐immune necrotizing glomerulonephritis (PING) is a small vessel renal vasculitis usually associated with the presence of antineutrophil cytoplasmic antibodies (ANCA) against myeloperoxidase or proteinase. A small proportion of PING patients do not have ANCA antibodies.

A condition known as Pauci‐immune necrotizing glomerulonephritis, or PING for short, is a type of kidney inflammation that affects small blood vessels. This condition is typically linked with the existence of certain antibodies, specifically antineutrophil cytoplasmic antibodies or ANCA, which target myeloperoxidase or proteinase. However, it's worth noting that a minor percentage of individuals diagnosed with PING do not possess these ANCA antibodies. A 24‐year‐old woman with no previous medical history arrived at the ER due to various symptoms including joint pain, fever, difficulty swallowing, and shortness of breath. Despite multiple symptoms suggesting systemic lupus erythematosus (SLE), this diagnosis was ruled out based on the EULAR/ACR 2019 classification criteria and laboratory tests. Other potential diagnoses such as rheumatoid arthritis (RA) and eosinophilic garnulomatosis with polyaniitis (EGPA) were also excluded based on respective criteria. The patient was treated with a 3‐day course of methylprednisolone, followed by prednisolone, which improved her creatinine levels. Subsequent tests for P‐ANCA and C‐ANCA were negative. A kidney biopsy confirmed necrotizing glomerulonephritis, consistent with pauci‐immune vasculitis. A bronchoscopy revealed bleeding and hemorrhage in her lungs, but bacterial culture analysis was negative. The patient was given piperacillin, tazobactam, and vancomycin for septic coverage, as well as intravenous immunoglobulin (IVIg), which led to symptom improvement.
Multidisciplinary management of implant failure: A case report
Authors: Samadi Alaa , Ismaili Zouheir , El Yamani Amal
Published: August 2024

Key Clinical Message

This case report presents the interest of multidisciplinary management of extreme peri‐implantitis requiring removal of implant emphasizing the different surgical and showing that the ovate pontic of conventional bridge is an optimal alternative for rehabilitation of the premolar sector, despite the fact that its main diffusion has been in the anterior sector due to the high demand aesthetic.

Peri‐implantitis leads to gradual peri‐implant bone loss. Severe and extreme cases lead to complete implant failure and imply lost implants have to be removed. Residual ridge deformity management after implant removal is one of the factors contributing to improved aesthetic and functional results. Various grafting procedures have been developed to achieve this goal. This report describes a case of implant removal from the upper right first premolar due to advanced peri‐implantitis in a 51‐year‐old female patient. Guided bone regeneration with a alloplastic bone graft and resorbable collagen membrane combined with roll pedicle connective tissue graftt was used for both socket and soft‐tissue augmentation. This was combined with ovate design conventional provisional bridge. After a 6‐month of healing phase, a perfect adaptation of the marginal gingiva around the provisional restoration was obtained. Cone beam computed tomography revealed significant bone fill and buccolingual dimensional stability. A conventional all‐ceramic bridge with an oval pontic design was chosen as a definitive prosthetic solution to compensate for edentulism and maintain the good aesthetic results. According to the encouraging result obtained in this clinical case, the conventional prosthetic restoration associated with surgical reconstruction of failing tissues can be considered as a successful treatment in the case of advanced peri‐implantitis requiring implant removal.
Direct Synthesis of Pd2+‐Rich Palladene Aerogels as Bifunctional Electrocatalysts for Formic Acid Oxidation Reaction and Oxygen Reduction Reaction
Authors: Wang Cui , Wei Wei , Georgi Maximilian , Hübner René , Steinbach Christine , Bräuniger Yannik , Schwarz Simona , Kaskel Stefan , Eychmüller Alexander
Published: August 2024

In this work, we developed a direct strategy to fabricate Palladene (i. e. Palladium metallene) aerogels and propose a temperature‐dependent growth mechanism. Besides the typical three‐dimensional networks and wrinkled surface morphologies, the as‐prepared
aerogel is endowed with abundant Pd2+. The as‐prepared
aerogel exhibits an excellent mass activity in the formic acid oxidation reaction and a good half‐wave potential in the oxygen reduction reaction in comparison with Pd/C and a Pd aerogel. This work expands the range of metal aerogels from the perspective of the building block units and demonstrates a direct approach to fabricate highly promising bifunctional electrocatalysts for fuel cells.
Updating strategy of safe operation control model for dense medium coal preparation process based on Bayesian network and incremental learning
Authors: Wang Jianwen , Chu Fei , Zhao Jianyu , Bao Wenchao , Wang Fuli
Published: August 2024

The effectiveness of control decisions provided by the safe operation control model for the dense medium coal preparation process may decline due to its inability to adapt to changing working conditions. To address this issue, this paper investigates a safe operation control model update strategy based on Bayesian network and incremental learning. This strategy can update the model structure and parameters according to different conditions, ensuring the effectiveness of the updated model. Considering that the old model has effective information to explain the new working conditions, the Bayesian network structure update learning method based on incremental learning is proposed. This method retains the components of the old model that can describe the joint probability distribution of the sampled data under the new working conditions while updating the remaining structure. This approach improves the efficiency of model updating. The simulation results show that the updated model obtained by the proposed method can effectively deal with new abnormal conditions.
Design, Synthesis, and Anti‐Prostate Cancer Potential of 2‐(4‐Nitrobenzyl) Malonates In Vitro and DAL Acute Oral Toxicity Assessment In Vivo
Authors: Hassan Ganesh Bharathi , Aruchamy Baladhandapani , Mudradi Srikrishna , Mohanty Sarthak , Padinjarathil Himabindu , Carradori Simone , Ramani Prasanna
Published: August 2024

New 4‐nitrobenzyl derivatives were designed and synthesised by nucleophilic substitution reactions of 4‐nitrobenzyl bromide with malonic acid and its derivatives. The synthesised molecules were characterised using mass analysis and spectroscopic techniques and tested for their antioxidant properties using various methods, such as nitric oxide, DPPH, and hydrogen peroxide radical scavenging methods. The anti‐inflammatory activities of the molecules were assessed using RBC membrane stabilisation and albumin denaturation methods. We evaluated the compounds’ potential anti‐prostate cancer activity using the DU145 cell line. The MTT assay determined the cell viability, indicating good anti‐proliferative activity. The molecule 3 c exhibited the highest potency, with a CTC50 of 11.83 μg/mL. Molecular dynamics simulations were performed to study the stability of the ligand within the protein after docking and the resulting protein‐ligand complex. The in vivo analysis of molecule 3 c in the DAL xenograft model demonstrated promising results. The increase in life span, reduction in tumor volume, and comparable effects to standard drugs are encouraging features that suggest that molecule 3 c may possess significant potential as an anti‐cancer agent. The research also implies that these molecules might be potential lead compounds for developing new prostate cancer drugs.
The French Medicinal Chemistry Society–SCT, an Historical Member of EFMC**
Authors: Deprez‐Poulain Rebecca , Duca Maria , George Nicolas , Deprez Benoit , Ortholand Jean‐Yves
Published: August 2024

The French Society of Medicinal Chemistry or “ Société de Chimie Thérapeutique ” (SCT) was founded in 1966. Since its inception, its mission has been to promote knowledge in the main fields of pharmaceutical research and development, in particular the research and validation of biological targets of therapeutic interest, the screening, design and optimization of drug candidates, chemical biology, medicinal chemistry, pharmacokinetics, metabolism and toxicity. Since 1964, the Society has organized an annual international congress (RICT), and later thematic days for young researchers and workshops on specific topics. The SCT is also a member of the European Federation for Medicinal Chemistry (EFMC) and organized the International Symposium on Medicinal Chemistry (ISMC) in Nice in 2022. Several new trends can be identified in the activities of the SCT, such as the organization of regular webinars, but also the recent creation of the Young MedChem Forum, as well as the distribution of a newsletter reporting scientific achievements in the French community and abroad, and an improved presence on social networks. These trends are in line with the current changes in the field in terms of scientific progress, means of communication in the community and with the public and inclusiveness.
Stem to prevent periprosthetic fracture after notching in total knee arthroplasty
Authors: Wan Qian , Zhang Aobo , Liu Yang , Chen Hao , Zhao Xue , Han Qing , Wang Jincheng
Published: August 2024

Improper osteotomy during total knee arthroplasty (TKA) can lead to anterior femoral notching, which increases the risk of periprosthetic fractures due to stress concentration. One potential solution is the addition of an intramedullary stem to the femoral component. However, the optimal stem length remains unclear. In this study, we aimed to determine the optimal stem length using finite element models. Finite element models of femurs were developed with unstemmed prostheses and prostheses with stem lengths of 50, 75, and 100 mm. Under squat loading conditions, the von Mises stress at the notch and stress distribution on four transversal sections of the femur were analyzed. Additionally, micromotion of the prosthesis–bone interface was evaluated to assess initial stability. The unstemmed prosthesis exhibited a von Mises stress of 191.8 MPa at the notch, which decreased to 43.1, 8.8, and 23.5 MPa for stem lengths of 50, 75, and 100 mm, respectively. The stress reduction on four selected femoral transversal sections compared with the unstemmed prosthesis was 40.0%, 84.4%, and 67.1% for stem lengths of 50, 75, and 100 mm, respectively. Micromotion analysis showed a maximum of 118.8 μm for the unstemmed prosthesis, which decreased significantly with the application of stems, particularly at the anterior flange. Intramedullary stems effectively reduced stress concentration at the femoral notch. The 50‐mm stem length provided the optimal combination of reduced notch stress, minimized stress‐shielding effect, and decreased micromotion at the anterior flange.
Sensitivity Enhancement of Ultra‐Wideline NMR by Progressive Saturation of the Proton Reservoir Under Magic‐Angle Spinning
Authors: Wolf Tamar , Goobes Yuval , Frydman Lucio
Published: August 2024

Solid‐state NMR of low‐γ nuclides is often characterized by low sensitivity and by significant spectral broadenings induced by the quadrupolar and the chemical‐shift anisotropy interactions. Herein, we introduce an indirect acquisition method, termed PROgressive Saturation of the Proton Reservoir Under Spinning (PROSPRUS), which could facilitate the acquisition of ultra‐wideline NMR spectra under magic‐angle spinning (MAS), in systems with a sufficiently long dipolar relaxation time, T1D. PROSPRUS NMR relies on the generation of so‐called second‐order dipolar order among abundant protons undergoing MAS, and on the subsequent depletion of this dipolar order by a series of looped cross‐polarization events, transferring the proton order into polarization of the low‐γ I‐nuclei as a function of the latter's offsets. While the spin dynamics of the ensuing experiment is complex, particularly when dealing with narrow I spectral lines, it is shown that PROSPRUS can lead to faithful lineshapes for ultra‐wideline spin‐1/2 and spin‐1 species, providing high sensitivity with extremely low RF power requirements. It is also shown that the ensuing 1H‐detected PROSPRUS experiments can efficiently characterize I‐spin lineshapes in excess of 1 MHz without having to retune electronics, while providing improvements in sensitivity per unit time over current broadband direct‐detection methods by up to a factor of four.
Coproporphyrin‐I as a Selective OATP1B Biomarker Can Be Used to Delineate the Mechanisms of Complex Drug–Drug Interactions: Cedirogant Case Study
Authors: Kikuchi Ryota , Qian Yuli , Badawi Mohamed , Savaryn John P. , Gannu Shashikanth , Eldred Ann , Hao Shuai , Salem Ahmed Hamed , Liu Wei , Klein Cheri E. , Mohamed Mohamed‐Eslam F.
Published: August 2024

Cedirogant is an inverse agonist of retinoic acid‐related orphan receptor gamma thymus developed for the treatment of chronic plaque psoriasis. Cedirogant induces cytochrome P450 (CYP) 3A4 while inhibiting P‐glycoprotein (P‐gp), breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP) 1B1, and OATP1B3 in vitro. Static drug–drug interactions (DDIs) predictions suggested possible clinical induction of CYP3A4, and inhibition of P‐gp, BCRP, and OATP1B1, leading to challenges in interpreting DDI studies between cedirogant and substrates of CYP3A, P‐gp, BCRP, and OATP1B1/3. Here the effects of cedirogant on the pharmacokinetics of two statin drugs were investigated in healthy participants. Coproporphyrin‐I (CP‐I), a selective endogenous OATP1B biomarker, was used to assess the impact of cedirogant on OATP1B. Cedirogant (375 mg once daily) increased rosuvastatin maximum plasma concentration (Cmax) and area under the plasma concentration curve (AUCtau) by 141% and 55%, respectively when co‐administered, whereas atorvastatin Cmax increased by 40% with no effect on its AUCtau compared with administration of rosuvastatin/atorvastatin alone. Cedirogant did not increase CP‐I exposures, indicating no clinical OATP1B inhibition. The increased rosuvastatin exposure and minimal change in atorvastatin exposure with co‐administration of cedirogant is attributed to BCRP inhibition and interplay between P‐gp/BCRP inhibition and CYP3A induction, respectively. Correlation analysis with data from two investigational drugs (glecaprevir and flubentylosin) demonstrated that OATP1B1 R‐value of > 1.5 and [Cmax,u]/[OATP1B1 IC50] of > 0.1 are associated with > 1.25‐fold increase in CP‐I Cmax ratio. This demonstrates the utility of CP‐I in disentangling mechanisms underlying a complex DDI involving multiple transporters and enzymes and proposes refined criteria for static OATP1B inhibition predictions.
The day after mowing: Time and type of mowing influence grassland arthropods
Authors: Berger Johanna L. , Staab Michael , Hartlieb Margarita , Simons Nadja K. , Wells Konstans , Gossner Martin M. , Vogt Juliane , Achury Rafael , Seibold Sebastian , Hemp Andreas , Weisser Wolfgang W. , Blüthgen Nico
Published: August 2024

Recent losses in the abundance and diversity of arthropods have been documented in many regions and ecosystems. In grasslands, such insect declines are largely attributed to land use, including modern machinery and mowing regimes. However, the effects of different mowing techniques on arthropods remain poorly understood. Using 11 years of data from 111 agricultural grassland plots across Germany, we analyzed the influence of various grassland management variables on the abundance and abundance‐accounted species richness of four arthropod orders: Araneae, Coleoptera, Hemiptera, and Orthoptera. The analysis focused on detailed mowing information, for example, days after mowing and mower type, and compared their effect with other aspects of grassland management, that is, rolling, leveling, fertilization, and grazing. We found strong negative effects of mowing on all four arthropod orders, with arthropod abundance being lowest directly after mowing and steadily increasing to three to seven times the abundance after 100 days post‐mowing. Likewise, Hemiptera and Coleoptera species richness was 30% higher 100 days after mowing. Mower width showed a positive effect on Orthoptera abundance, but not on the other arthropods. Arthropod abundance and Coleoptera species richness were lowest when a mulcher was used compared to rotary or bar mowers. In addition to mowing, intensive grazing negatively affected Orthoptera abundance but not the other orders. Mowing represents a highly disturbing and iterative stressor with negative effects on arthropod abundance and diversity, likely contributed by mowing‐induced mortality and habitat alteration. While modifications of mowing techniques such as mower type or mowing height and width may help to reduce the negative impact of mowing on arthropods, our results show that mowing itself has the most substantial negative effect. Based on our results, we suggest that reduced mowing frequency, omission of mowing in parts of the grassland (refuges), or extensive grazing instead of mowing have the greatest potential to promote arthropod populations.
Synthetic Strategies and Applications of Fluorine‐Containing Bridged Bicyclic Compounds
Authors: Baldon Simone , Dell'Amico Luca , Cuadros Sara
Published: August 2024

Bridged bicyclic compounds (BBCs) have recently emerged as effective 3D‐isosteres of planar aryl and heteroaryl rings. Current synthetic endeavours are devoted to accessing these complex structures bearing functionalities in different positions of the aliphatic rings. Of particular interest is the incorporation of F‐containing motifs, since it allows the generation of isosteric units with improved physicochemical properties, including lipophilicity, water solubility, or oxidative resistance.
Cyclic test and analysis of UHTCC‐enhanced buckling‐restrained steel plate shear walls
Authors: Tong Jing‐Zhong , Wang Ling‐Qi , Wu Ruo‐Min , Hou Jian , Li Qing‐Hua , Xu Shi‐Lang
Published: August 2024

The ultra‐high toughness cementitious composite (UHTCC) has the tensile strain‐hardening characteristic and an excellent ability to prevent tensile cracking. To enhance the seismic and durability performance of the conventional buckling‐restrained steel plate shear wall (BRSPSW), UHTCC‐enhanced BRSPSW (UBRSPSW) was proposed in this paper as a new type of lateral bearing system. The buckling of the inner steel plate is restrained by UHTCC‐normal concrete (NC) functionally graded panels, where the panels are composed of UHTCC and NC layers. In this study, experimental and numerical research was carried out on the UBRSPSWs. Six specimens were tested to investigate the seismic behavior of the UBRSPSW. Parameters including the number of stiffeners, the thickness of UHTCC‐NC functionally graded panels, the material of restraining panels, and the gap between the inner steel plate and restraining panels were considered in the test design. Mechanical response and failure modes of the structures under cyclic loads were analyzed. The obtained hysteretic curves and corresponding skeleton curves indicated that the proposed design had excellent seismic performance. Compared to the steel plate shear wall (SPSW), the load‐bearing capacity of UBRSPSW was improved by 13%, respectively. The appearance of macrocracks was delayed by a drift angle of 1.2%. In addition, a refined finite element (FE) model was developed and validated by the results obtained from experiments. The development and distribution of bending moments in the restraining panels were extracted based on the FE method. Then, the loading capacity design method of restraining panels and a theoretical model for controlling the crack width of restraining panels were proposed. The research results of this paper can provide useful suggestions for the seismic design of UBRSPSWs.
Identification of promising lactic acid bacteria for the fermentation of lupine‐ and faba bean‐based substrates to produce refreshing protein‐rich beverages—A strain screening
Authors: Ritter Stefan , Luber Carolin , Gastl Martina , Becker Thomas
Published: August 2024

Lupines and faba beans are rising stars among legumes as sources of valuable, vegan plant‐based proteins. To enter new application areas like the production of protein‐rich refreshing beverages, the typical beany aroma impression has to be overcome, and the sensory appearance has to be improved, as it can be accomplished with lactic acid fermentation. An extensive strain screening of 70 lactic acid bacteria from 16 genera was performed to identify suitable strains to transform substrates made from lupines and faba beans into refreshing beverages and to improve their sensory characteristics. By analyzing carbohydrate utilization, production of organic acids and aroma compounds, and sensory appearance, 22 strains for lupine and eight strains for faba bean were preselected. Subsequently, the most suitable strains (five for lupine and three for faba beans) were identified by a trained sensory panel, and finally their growth kinetics were discussed. Generally, the aroma profile varied highly with the utilized strain. However, by selecting suitable strains, the beany impression can be highly reduced and pleasant aroma impressions (e.g., fruity and buttermilk) can be added. Most strikingly, it was proven that using germinated lupines and faba beans instead of raw ones can bypass the usual growth restriction, and the strain selection can be focused exclusively on sensory aspects. This opens the option to use strains usually excluded for the fermentation of legumes due to their lack of utilization of the legume‐typical α‐galactosides.
Exploring pleiotropy in Mendelian randomisation analyses: What are genetic variants associated with ‘cigarette smoking initiation’ really capturing?
Authors: Reed Zoe E. , Wootton Robyn E. , Khouja Jasmine N. , Richardson Tom G. , Sanderson Eleanor , Davey Smith George , Munafò Marcus R.
Published: August 2024

Genetic variants used as instruments for exposures in Mendelian randomisation (MR) analyses may have horizontal pleiotropic effects (i.e., influence outcomes via pathways other than through the exposure), which can undermine the validity of results. We examined the extent of this using smoking behaviours as an example. We first ran a phenome‐wide association study in UK Biobank, using a smoking initiation genetic instrument. From the most strongly associated phenotypes, we selected those we considered could either plausibly or not plausibly be caused by smoking. We examined associations between genetic instruments for smoking initiation, smoking heaviness and lifetime smoking and these phenotypes in UK Biobank and the Avon Longitudinal Study of Parents and Children (ALSPAC). We conducted negative control analyses among never smokers, including children. We found evidence that smoking‐related genetic instruments were associated with phenotypes not plausibly caused by smoking in UK Biobank and (to a lesser extent) ALSPAC. We observed associations with phenotypes among never smokers. Our results demonstrate that smoking‐related genetic risk scores are associated with unexpected phenotypes that are less plausibly downstream of smoking. This may reflect horizontal pleiotropy in these genetic risk scores, and we would encourage researchers to exercise caution this when using these and genetic risk scores for other complex behavioural exposures. We outline approaches that could be taken to consider this and overcome issues caused by potential horizontal pleiotropy, for example, in genetically informed causal inference analyses (e.g., MR) it is important to consider negative control outcomes and triangulation approaches, to avoid arriving at incorrect conclusions.
Piecing together Pakistan's health system and global health security
Authors: Ahmed Abdullah Muhammad , Shaikh Babar Tasneem , Khan Shahzad Ali
Published: August 2024

Pakistan's health system has a critical role to play in global health security, however, it faces numerous structural and systemic challenges while contributing to international health efforts. Understanding the dynamics of health system is essential for developing effective strategies to prevent, detect, and respond to health emergencies, ensuring regional stability, and the overall global health security This paper documents the strengths and weaknesses of Pakistan's health systems, the impact of the COVID‐19 pandemic, challenges such as funding constraints and fragmented healthcare delivery, threats including antimicrobial resistance, and the importance of international collaboration. Anti‐microbial particularly multi‐drug resistance, food safety in emergencies, surge capacity of the frontline workforce, patient safety at the health care facilities to curtail healthcare associated infections, and strengthening the points of entry are still the areas that need special attention. To optimise the system's performance, governance and accountability mechanisms are necessary to be put in place under the auspices of national public health agency. Pakistan has the potential to transform its health system by addressing these critical areas and improve its preparedness and readiness for any future health emergency of this scale.
Enhancing heat exchanger performance with perforated/non‐perforated flow modulators generating continuous/discontinuous swirl flow: A comprehensive review
Authors: Rahman Md Atiqur , Hasnain S. M. Mozammil
Published: August 2024

Heat exchangers are crucial in transferring heat and finding applications across various industries. Numerous strategies have been devised to improve and optimize the heat transfer process within these systems. Among these, passive methods have garnered significant attention for their ability to operate without external power consumption. This article examines the recent experimental and computational studies conducted by researchers since 2018 on passive enhancement techniques, especially twisted tape, wire coil, swirl flow generator, and others, to boost the thermal efficiency of heat exchangers and aid designers in adopting passive augmentation methods for compact heat exchangers. Recently, researchers' new class of flow maldistribution devices, referred to as swirl flow devices, has gained attention; which enhances convective heat transfer by introducing swirl into the main flow and disrupting the boundary layer at the tube surface through alterations in surface geometry. Twisted tape inserts are devices that demonstrate better performance in laminar flow compared to turbulent flow. Conversely, other passive techniques like ribs, conical nozzles, and conical rings are generally more effective in turbulent flow than laminar flow. A recent research trend is the utilization of nanofluids in combination with other passive heat transfer enhancement techniques like turbulators, ribs, and twisted tape inserts in heat exchangers, which can reduce exergy losses and improve overall convective heat transfer coefficient and effectiveness of heat exchanger.
Falling pass rates on the North American Pharmacist Licensure Examination signal an emerging crisis for a growing number of pharmacy schools
Authors: Brown Daniel L.
Published: August 2024

The North American Pharmacist Licensure Examination (NAPLEX) is a major assessment metric for graduates pursuing licensure and the institutions from which they graduated. Before 2014, the mean NAPLEX first‐time pass rate was roughly 95% every year. Mean pass rates have fallen dramatically since then to less than 80%, with many schools currently unable to achieve a 70% pass rate. Such a drastic decline in NAPLEX performance constitutes a crisis for many schools. Changes to the exam blueprint, administration, and scoring provide a partial explanation for the decline, but the issue of cause ultimately comes down to one simple question: What has changed over the last 10 years that is making it more difficult for graduates to pass NAPLEX on the first attempt? The effects of excessive academic expansion, beginning in 2000, cannot be overlooked. The newest schools, established after 2009, and accelerated (3‐year) programs, many of which are also new, appear to be particularly vulnerable. In 2023, 16 pharmacy schools had first‐time pass rates below 65%. Nine (56%) of those schools opened after 2009 and seven (44%) were accelerated programs. Newer schools have had to compete for a limited supply of qualified faculty, administrators, preceptors and experiential training sites, while also striving to meet enrollment targets amid a dwindling applicant pool. The ability to overcome the NAPLEX crisis depends on first establishing a more effective process of assessing NAPLEX results—one that measures the right metrics in the right way—and upholds fair, but rigorous, quality standards. Stakeholders need access to actionable information and the most relevant, useful data available. The purpose of this article is to provide evidence that the Academy is facing a legitimate crisis and offer four recommendations by which assessment and understanding of the crisis can be enhanced.