bluuebunny/crossref_metadata_2025 huggingface dataset:
Iodine‐Mediated Regioselective Radical Cyclization of o‐Vinylaryl Isocyanides with Disulfides/Diselenides Leading to 2‐Chalcogenated Quinolines
Authors: Li Ya‐Nan , Chen Fan , Zhang Xing‐Guo , Tu Hai‐Yong
Published: September 2023

An iodine‐mediated radical cyclization of o‐vinylaryl isocyanides with disulfides or diselenides was developed. The atom‐economic reaction provides a method for regioselective construction of the 2‐chalcogenated quinolines in 42–93% yields by incorporation of both chalcogen atoms of disulfides or diselenides into quinolines.
Beyond Extracellular Vesicles: Hybrid Membrane Nanovesicles as Emerging Advanced Tools for Biomedical Applications
Authors: Sun Meng , Yang Jiani , Fan Yueyun , Zhang Yinfeng , Sun Jian , Hu Min , Sun Ke , Zhang Jinfeng
Published: September 2023

Extracellular vesicles (EVs), involved in essential physiological and pathological processes of the organism, have emerged as powerful tools for disease treatment owing to their unique natural biological characteristics and artificially acquired advantages. However, the limited targeting ability, insufficient production yield, and low drug‐loading capability of natural simplex EVs have greatly hindered their development in clinical translation. Therefore, the establishment of multifunctional hybrid membrane nanovesicles (HMNVs) with favorable adaptability and flexibility has become the key to expanding the practical application of EVs. This timely review summarizes the current progress of HMNVs for biomedical applications. Different HMNVs preparation strategies including physical, chemical, and chimera approaches are first discussed. This review then individually describes the diverse types of HMNVs based on homologous or heterologous cell membrane substances, a fusion of cell membrane and liposome, as well as a fusion of cell membrane and bacterial membrane. Subsequently, a specific emphasis is placed on the highlight of biological applications of the HMNVs toward various diseases with representative examples. Finally, ongoing challenges and prospects of the currently developed HMNVs in clinical translational applications are briefly presented. This review will not only stimulate broad interest among researchers from diverse disciplines but also provide valuable insights for the development of promising nanoplatforms in precision medicine.
Near‐Infrared Light‐Induced Reversible Deactivation Radical Polymerization: Expanding Frontiers in Photopolymerization
Authors: Wu Zilong , Boyer Cyrille
Published: September 2023

Photoinduced reversible deactivation radical polymerization (photo‐RDRP) or photoinduced controlled/living radical polymerization has emerged as a versatile and powerful technique for preparing functional and advanced polymer materials under mild conditions by harnessing light energy. While UV and visible light (λ = 400–700 nm) are extensively employed in photo‐RDRP, the utilization of near‐infrared (NIR) wavelengths (λ = 700–2500 nm) beyond the visible region remains relatively unexplored. NIR light possesses unique properties, including enhanced light penetration, reduced light scattering, and low biomolecule absorption, thereby providing opportunities for applying photo‐RDRP in the fields of manufacturing and medicine. This comprehensive review categorizes all known NIR light‐induced RDRP (NIR‐RDRP) systems into four mechanism‐based types: mediation by upconversion nanoparticles, mediation by photocatalysts, photothermal conversion, and two‐photon absorption. The distinct photoinitiation pathways associated with each mechanism are discussed. Furthermore, this review highlights the diverse applications of NIR‐RDRP reported to date, including 3D printing, polymer brush fabrication, drug delivery, nanoparticle synthesis, and hydrogel formation. By presenting these applications, the review underscores the exceptional capabilities of NIR‐RDRP and offers guidance for developing high‐performance and versatile photopolymerization systems. Exploiting the unique properties of NIR light unlocks new opportunities for synthesizing functional and advanced polymer materials.
Multi‐Mode Vibrational Triboelectric Nanogenerator for Broadband Energy Harvesting and Utilization in Smart Transmission Lines
Authors: Zhang Xiaosong , Yu Yang , Xia Xiao , Zhang Weiqi , Cheng Xiaojun , Li Hengyu , Wang Zhong Lin , Cheng Tinghai
Published: September 2023

The advantages of the triboelectric nanogenerator (TENG) in environmental energy harvesting and utilization determine that they have great development potential in the digital application of power grids. This work focuses on the harvesting and utilization of vibration energy from transmission lines, specifically in the context of breeze vibrations and sub‐span oscillations. To this end, this work proposes a novel multi‐mode vibrational triboelectric nanogenerator (MV‐TENG) and three smart transmission line application strategies based on the MV‐TENG. The MV‐TENG design consists of an S‐beam to broaden the frequency response range by reducing high‐order modal frequencies, and a pair of allegro electrodes to efficiently harvest horizontal and vertical vibration energy. The MV‐TENG demonstrates the capability to harvest vibration energy within a range of 1–3.5 Hz horizontally and 4 Hz, 9–60 Hz vertically, covering the occurrence range of breeze vibrations and sub‐span oscillations of transmission line effectively. Three application strategies include self‐powered tower obstacle alerting, temperature and humidity online monitoring, and high‐temperature wireless warning of transmission lines based on MV‐TENG. In summary, this work presents a comprehensive implementation scheme for digitally integrating TENGs into smart transmission lines, thereby facilitating the engineering development of TENG technology in grid systems.
Carbon‐negative syngas production: A comprehensive assessment of biomass pyrolysis coupling chemical looping reforming
Authors: Liu Gen , Zhang Rongjiang , Sun Zhongshun , Zhang Bo , Wang Zhichao , Liu Jingjun , Yang Bolun , Wu Zhiqiang
Published: September 2023

This article introduces a pyrolysis chemical looping reforming (PCLR) process that produces carbon‐negative syngas in autothermal operation. To enhance the system's carbon negativity, a process configuration with oxygen carrier two‐stage regeneration is adopted, enabling internal CO2 utilization. The PCLR process is systematically evaluated and compared to chemical looping gasification and steam gasification processes in the process performance, energy efficiency, and environmental impact using a process model. Results reveal significant improvements over chemical looping gasification, including 69%, 45%, and 4% improvement in syngas yield, energy efficiency, and environmental benefit. Process analysis demonstrates that decoupling volatile reforming from pyrolysis and combustion enhances syngas quality, energy efficiency, and process flexibility. While the two‐stage regeneration sacrifices syngas production, it contributes to a 4% increase in carbon negativity and a 15% reduction in carbon emissions. Thus, the PCLR process effectively overcomes the limitations of chemical looping gasification systems and exhibits excellent process intensification performance.
Posterior reversible encephalopathy syndrome in a child, following splenectomy under combined general and spinal anaesthesia
Authors: Gallop L. , McNeillis N.
Published: September 2023

Posterior reversible encephalopathy syndrome is a rare and serious condition that presents with acute neurological symptoms with characteristic changes on imaging. It can lead to substantial morbidity and mortality, but can be reversible if recognised and treated. Here, we report a case of posterior reversible encephalopathy syndrome in a child post‐splenectomy under general anaesthesia with spinal anaesthesia. As far as we are aware, this condition has not previously been described in relation to spinal anaesthesia in the paediatric population. This case demonstrates the importance of recognising blood pressure changes in children, which can be challenging due to age‐, sex‐ and height‐related centiles for blood pressure measurements. Posterior reversible encephalopathy syndrome should be considered as a differential diagnosis for headache in a patient that has had a spinal anaesthesia.
Guidelines in Practice: Minimally Invasive Surgery
Authors: Speth Jennifer
Published: September 2023

During minimally invasive surgery (MIS), surgeons create small and percutaneous incisions to access internal structures without open surgical incisions. Some MIS equipment is complex and challenging for perioperative nurses to manage. Patients also can experience life‐threatening complications during MIS procedures. The updated AORN “Guideline for minimally invasive surgery” provides recommendations that perioperative nurses can use when caring for patients undergoing MIS procedures. This article provides an overview of the guideline and discusses several recommendations, including creating a safe environment in which to perform MIS procedures; using gas distension media, irrigation and fluid distension media, and computer‐assisted navigation and robotics; and performing intraoperative magnetic resonance imaging in a hybrid OR. It also includes a scenario describing care of a patient undergoing a hysteroscopy. Perioperative nurses who care for patients undergoing MIS procedures should review the guideline in its entirety and apply the recommendations as applicable in their practice.
Protective effect of bromelain on some metabolic enzyme activities in tyloxapol‐induced hyperlipidemic rats
Authors: Sulumer Ayşe Nurseli , Palabıyık Esra , Avcı Bahri , Uguz Handan , Demir Yeliz , Serhat Özaslan Muhammet , Aşkın Hakan
Published: September 2023

Elevation of one or more plasma lipids, such as phospholipids, cholesterol esters, cholesterol, and triglycerides, is known as hyperlipidemia. In humans and experimental animals, bromelain, the primary active ingredient isolated from pineapple stems, has several positive effects, including anti‐tumor growth, anticoagulation, and anti‐inflammation. Hence, the purpose of this study was to determine the possible protective impact of bromelain on some metabolic enzymes (paraoxonase‐1, glutathione S‐transferase, glutathione reductase, sorbitol dehydrogenase [SDH], aldose reductase [AR], butyrylcholinesterase [BChE], and acetylcholinesterase [AChE]), activity in the heart, kidney, and liver of rats with tyloxapol‐induced hyperlipidemia. Rats were divided into three groups: control group, HL‐control group (tyloxapol 400 mg/kg, i.p. administered group), and HL+bromelain (group receiving bromelain 250 mg/kg/o.d. prior to administration of tyloxapol 400 mg/kg, i.p.). BChE, SDH, and AR enzyme activities were significantly increased in all tissues in HL‐control compared to the control, whereas the activity of other studied enzymes was significantly decreased. Bromelain had a regulatory effect on all tissues and enzyme activities. In conclusion, these results prove that bromelain is a new mediator that decreases hyperlipidemia.
Characterization and discrimination of spike protein in SARS‐CoV‐2 virus‐like particles via surface‐enhanced Raman spectroscopy
Authors: Akdeniz Munevver , Al‐Shaebi Zakarya , Altunbek Mine , Bayraktar Canan , Kayabolen Alisan , Bagci‐Onder Tugba , Aydin Omer
Published: September 2023

Non‐infectious virus‐like particles (VLPs) are excellent structures for development of many biomedical applications such as drug delivery systems, vaccine production platforms, and detection techniques for infectious diseases including SARS‐CoV‐2 VLPs. The characterization of biochemical and biophysical properties of purified VLPs is crucial for development of detection methods and therapeutics. The presence of spike (S) protein in their structure is especially important since S protein induces immunological response. In this study, development of a rapid, low‐cost, and easy‐to‐use technique for both characterization and detection of S protein in the two VLPs, which are SARS‐CoV‐2 VLPs and HIV‐based VLPs was achieved using surface‐enhanced Raman spectroscopy (SERS). To analyze and classify datasets of SERS spectra obtained from the VLP groups, machine learning classification techniques including support vector machine (SVM), k‐nearest neighbors (kNN), and random forest (RF) were utilized. Among them, the SVM classification algorithm demonstrated the best classification performance for SARS‐CoV‐2 VLPs and HIV‐based VLPs groups with 87.5% and 92.5% accuracy, respectively. This study could be valuable for the rapid characterization of VLPs for the development of novel therapeutics or detection of structural proteins of viruses leading to a variety of infectious diseases.
Climate risks to the renewable energy sector: Assessment and adaptation within energy companies
Authors: Juhola Sirkku , Laurila Anna‐Greta , Groundstroem Fanny , Klein Johannes
Published: September 2023

The importance of the renewable energy sector in mitigating climate change has received plenty of attention over the years, but climate risks to the renewable energy sector, and the need for adaptation within energy companies, have been largely overlooked. Subsequently, not much is known about the current state of climate risk assessments and adaptation measures within the renewable energy sector. This study addresses this gap by categorising different types of climate risks faced by renewable energy companies and the measures that are used to prepare and adapt to them. We summarise the existing literature on climate risks and adaptation within the renewable energy sector and carry out an interview‐based qualitative case study regarding energy companies' perception and assessment of climate risks in Finland. The results show that while companies are aware of climate risks, particularly concerning the green transition, climate risks are not comprehensively assessed, and adaptation measures mainly account for direct physical risks with little regard for more systemic and complex risks, such as cross‐border impacts or cascading risks.
Risk factors associated with overall survival in patients with multiple myeloma following carfilzomib treatment: A retrospective study from a large claims database in Japan
Authors: Hagiwara Hiromi , Nakayama Takafumi , Hashimoto Hiroya , Kusumoto Shigeru , Fukuta Hidekatsu , Kamiya Takeshi , Ikuta Koichi , Iida Shinsuke
Published: September 2023

Background

Carfilzomib is a selective proteasome inhibitor approved for treating relapsed or refractory multiple myeloma (RRMM). Carfilzomib improves overall survival (OS) and progression‐free survival (PFS); however, treatment with carfilzomib results in a higher incidence of cardiovascular and renal toxicity. More than 70% of patients with RRMM in clinical practice do not meet the eligibility criteria for randomized clinical trials (RCT). OS and PFS are negatively influenced by complications, concomitant medications and prior treatments. Therefore, we assessed the risk factors influencing the OS and time to next treatment (TTNT) in the real world. TTNT has emerged as a relevant alternative clinical endpoint to PFS.

Methods

A retrospective analysis of a large claims database prepared during the post‐marketing stages in Japan was performed. The patients treated with carfilzomib for the first time were identified. Multivariable Cox proportional hazards regression analysis was performed to evaluate the risk factors influencing OS and TTNT following carfilzomib treatment.

Results

A total of 732 patients with RRMM who received carfilzomib‐containing chemotherapy between April 2014 and September 2021 were identified. Multivariable Cox regression analysis for OS and TTNT showed a significantly higher hazard ratio (HR) of 1.48 (95% confidence interval [Cl]: 1.10–2.00; p = 0.010) and 1.38 (95% Cl: 1.15–1.65; p < 0.001), respectively, for patients with renal impairment compared to those without renal impairment. Multivariable Cox regression analysis for OS and TTNT showed a significantly higher HR of 1.80 (95% Cl: 1.27–2.55; p = 0.0010) and 1.38 (95% Cl: 1.14–1.66; p < 0.001), respectively, for patients with prior lenalidomide treatment compared to those without prior lenalidomide treatment.

Conclusion

Complication of renal impairment and prior lenalidomide treatment could be risk factors influencing OS and TTNT during carfilzomib treatment.
Tumor regression grade combined with post‐therapy lymph node status: A novel independent prognostic factor for patients treated with neoadjuvant therapy followed by surgery in locally advanced gastroesophageal junction and gastric carcinoma
Authors: Yin Hongyan , Yao Qian , Xie Yi , Niu Dongfeng , Jiang Wenya , Cao Huiying , Feng Xujiao , Li Yanyan , Li Yilin , Zhang Xiaotian , Shen Lin , Chen Yang
Published: September 2023

Background

Tumor regression grade (TRG) is a measure of histopathological response to neoadjuvant therapy (NAT). Post‐therapy lymph node (ypN) metastasis was reported as a prognostic factor. However, the evaluation of the treatment effectiveness of NAT has not been well studied. Here, we explored whether TRG combined with ypN status could be a prognostic factor for gastroesophageal junction (GEJ) and gastric cancer (GC). Besides, we aimed at making clear the association of different neoadjuvant regimens with different TRG and ypN status.

Methods

376 patients with GEJ or GC accepting NAT in Peking University Cancer Hospital were retrospectively collected from January 1, 2003 to June 30, 2021. According to TRG and ypN status, patients were innovatively categorized into four groups: TRG0N0, TRG1‐3N0, TRG0‐1N+, and TRG2‐3N+. We applied Kaplan–Meier method and log‐rank test to testify the differences in disease free survival (DFS) and overall survival (OS) among four groups. Univariate and multivariate analyses were performed to examine the relationships between TRG combined with ypN status and prognosis.

Results

We observed significant survival differences among the four groups (p < 0.001, respectively). Median DFS and OS of patients with TRG0N0, TRG1‐3N0, and TRG0‐1N+ were not reached, whereas these of patients with TRG2‐3N+ were 17.37 months (95% CI, 14.14–20.60 months) and 39.97 months (95% CI, 27.05–52.89 months). TRG combined with ypN status was still an independent predictor for both DFS (p < 0.001) and OS (p < 0.001) in multivariate analysis. Chi‐squared test showed TRG combined with ypN status was significantly associated with different preoperative treatments (p < 0.001). Patients receiving immunotherapy achieved the highest TRG0N0 rate (31.9%).

Conclusion

Our results demonstrate that TRG combined with ypN status is a novel independent predictor of both DFS and OS in resectable, locally advanced GEJ and GC. Neoadjuvant immunotherapy achieved the highest TRG0N0 rate.
UK secondary school therapists' online communication with their clients and future intentions
Authors: Hennigan Jeanette , Goss Stephen P
Published: September 2023

Aims

This study sought to understand: (1) UK school counsellors' use of computer technology to communicate with pupils as of March 2014; (2) perceived barriers to its further implementation; and (3) practitioners' expectations regarding future use of online therapy, to extend understanding of these issues in UK secondary schools. It is the first study of its kind to be carried out in the United Kingdom.

Method

A pluralist, mixed‐methods approach utilised quantitative and thematic qualitative analysis of an Internet survey of UK secondary schools.

Results

Of 3753 schools approached, 246 responded, and of these, 45% had no online communication with their clients and 52% were using various forms of online communication; 43% used online communication (mostly email) for administrative purposes; and 9% offered therapy via email, Skype and Face Time (3% did not respond). The three main motivators for developing therapeutic contact online were as follows: evidence of reaching pupils with psychological barriers to accessing face‐to‐face help, evidence of demand from pupils and access to appropriate training. The main perceived deterrents were as follows: impact on the quality of the relationship, issues around confidentiality, and impact of lack of visual and auditory cues.

Conclusion

This mixed landscape in terms of current and planned future use of technology by school counsellors revealed perceived practical and ethical challenges. However, it is notable that all of these can be addressed using currently available resources, for example through exposure to existing literature and research, and through specialist training.
Pediatric primary intraventricular hemorrhage: A case report of isolated fourth ventricle hemorrhage in a 10‐year‐old boy
Authors: Das Aswith , Bhadran Biju , Sanker Vivek , Suresh Vinay , Agarwal Pratik , Dave Tirth
Published: September 2023

Key Clinical Message

Primary intraventricular hemorrhage (PIVH) is a rare condition in pediatric patients, presenting with headache, vomiting, and altered mental status. Surgical interventions, such as external ventricular drain placement, followed by ventriculoperitoneal shunting, show promising outcomes. Further research is needed to enhance understanding and optimize management strategies for pediatric PIVH.

This case report describes a 10‐year‐old boy with isolated primary intraventricular hemorrhage (PIVH) in the fourth ventricle, shedding light on its clinical presentation and management challenges. The patient presented with headache, vomiting, and altered sensorium, and was subsequently diagnosed with obstructive hydrocephalus due to intraventricular bleeding. Emergency external ventricular drain (EVD) insertion was performed, followed by ventriculoperitoneal shunt placement, resulting in a favorable outcome. The etiology of PIVH in children differs from that in adults, with arteriovenous malformations, Moyamoya disease, and aneurysms being commonly implicated causes. Management strategies for pediatric PIVH are challenging due to limited research, but EVD placement and surgical interventions have shown promise.
Surgical treatment for coarctation of the aorta
Authors: Niwa Kosuke , Nishikawa Hiroshi , Ueda Daisuke , Yamashita Keigo
Published: September 2023

Key Clinical Message

Surgical treatment is a better option for coarctation of the aorta.

A 56‐year‐old man was admitted to the hospital due to chest pain. Computed tomography showed severe coarctation of the aorta distal to the left subclavian artery, with poststenotic dilatation of the descending aorta. A descending aortic replacement was performed in an uneventful manner. The postoperative course was good without symptoms.
Acquired syphilis with flat condyloma in a 3 year‐old girl: A case report
Authors: Hu Qing‐fu , Li Kun‐jie
Published: September 2023

Key Clinical Message

The incidence of syphilis in young children is very low, with acquired syphilis exceptionally rare. A 3 year‐old girl presented to our service with a reddish‐brown rash on the external genitals and perianal area. The rash had been apparent for a period of 1 week. The girl was asymptomatic and had no history of sexual contact. Syphilis was suspected and the Treponema pallidum particle agglutination test (TPPA) was found to be positive, as well as the rapid plasma regin ring card test (RPR), with a titer of 1:64. The girl was diagnosed with toddler acquired secondary syphilis. The girl was cured after three treatments with penicillin. This report points out the need for clinicians to be aware of nonsexually transmitted syphilis, acquired in daily life by children without a history of sexual contact.
An Efficient Approach for Quantifying the Mechanical Degradation of Ni‐Rich NMC‐based Cathodes for Lithium‐Ion Batteries using Nano‐XCT Analysis
Authors: Goldbach Daniel , Gluch Jürgen , Graf Tanja , Gaus Michael , Käbitz Stefan , Zillmer Michael , Krewer Ulrike
Published: September 2023

LiNi0.8Co0.1Mn0.1O2 has emerged as a promising electrode material for automotive lithium‐ion batteries due to its high specific discharge capacity, cost‐effectiveness, and reduced cobalt content. However, despite all mentioned beneficial attributes, the widespread adoption of this material class is impeded by active material degradation during cycling operation, which is linked to performance loss. This study compares scanning electron microscopy images and nano X‐ray computed tomography scans with a 3D reconstruction of pristine and cycle‐aged battery electrodes to determine structural changes over cycle life. Although a very moderate current rate was chosen for the cycle test, which suggests a homogeneous load across the entire electrode, particle fracture varied across electrode thickness and particle size. A quantitative analysis of the active material‘s gray scale value distribution reveals severe degradation near the separator interface with a reciprocal relationship to particle radius. Remarkably, particle shape and size remain relatively unchanged despite cracking, eliminating the need to adjust these parameters in aging simulations. Moreover, it underscores the practical significance of particle cracking, as it can significantly impact the electrode‘s performance. Thus, analyzing changes in particle shape and size alone is insufficient, and a comprehensive exploration of the particle interior using nano‐XCT is necessary.
Characterization of mismatch‐repair/microsatellite instability‐discordant endometrial cancers
Authors: Riedinger Courtney J. , Esnakula Ashwini , Haight Paulina J. , Suarez Adrian A. , Chen Wei , Gillespie Jessica , Villacres Alyssa , Chassen Alexis , Cohn David E. , Goodfellow Paul J. , Cosgrove Casey M.
Published: September 2023

Background

Mismatch‐repair (MMR)/microsatellite instability (MSI) status has therapeutic implications in endometrial cancer (EC). The authors evaluated the concordance of testing and factors contributing to MMR expression heterogeneity.

Methods

Six hundred sixty‐six ECs were characterized using immunohistochemistry (IHC), MSI testing, and mut‐L homolog 1 (MLH1) methylation. Select samples underwent whole‐transcriptome analysis and next‐generation sequencing. MMR expression of metastatic/recurrent sites was evaluated.

Results

MSI testing identified 27.3% of cases as MSI‐high (n = 182), MMR IHC identified 25.1% cases as MMR‐deficient (n = 167), and 3.8% of cases (n = 25) demonstrated discordant results. A review of IHC staining explained discordant results in 18 cases, revealing subclonal loss of MLH1/Pms 1 homolog 2 (PMS2) (n = 10) and heterogeneous MMR IHC (mut‐S homolog 6 [MSH6], n = 7; MLH1/PMS2, n = 1). MSH6‐associated Lynch syndrome was diagnosed in three of six cases with heterogeneous expression. Subclonal or heterogeneous cases had a 38.9% recurrence rate (compared with 16.7% in complete MMR‐deficient cases and 9% in MMR‐proficient cases) and had abnormal MMR IHC results in all metastatic recurrent sites (n = 7). Tumors with subclonal MLH1/PMS2 demonstrated 74 differentially expressed genes (determined using digital spatial transcriptomics) when stratified by MLH1 expression, including many associated with epithelial–mesenchymal transition.

Conclusions

Subclonal/heterogeneous MMR IHC cases showed epigenetic loss in 66.7%, germline mutations in 16.7%, and somatic mutations in 16.7%. MMR IHC reported as intact/deficient missed 21% of cases of Lynch syndrome. EC with subclonal/heterogeneous MMR expression demonstrated a high recurrence rate, and metastatic/recurrent sites were MMR‐deficient. Transcriptional analysis indicated an increased risk for migration/metastasis, suggesting that clonal MMR deficiency may be a driver for tumor aggressiveness. Reporting MMR IHC only as intact/deficient, without reporting subclonal and heterogeneous staining, misses opportunities for biomarker‐directed therapy.

Plain Language Summary

Endometrial cancer is the most common gynecologic cancer, and 20%–40% of tumors have a defect in DNA proofreading known as mismatch‐repair (MMR) deficiency.

These results can be used to guide therapy.

Tests for this defect can yield differing results, revealing heterogeneous (mixed) proofreading capabilities.

Tumors with discordant testing results and mixed MMR findings can have germline or somatic defects in MMR genes.

Cells with deficient DNA proofreading in tumors with mixed MMR findings have DNA expression profiles linked to more aggressive characteristics and cancer spread.

These MMR‐deficient cells may drive tumor behavior and the risk of spreading cancer.
Utilization of OATP1B Biomarker Coproporphyrin‐I to Guide Drug–Drug Interaction Risk Assessment: Evaluation by the Pharmaceutical Industry
Authors: Kikuchi Ryota , Chothe Paresh P. , Chu Xiaoyan , Huth Felix , Ishida Kazuya , Ishiguro Naoki , Jiang Rongrong , Shen Hong , Stahl Simone H. , Varma Manthena V.S. , Willemin Marie‐Emilie , Morse Bridget L.
Published: September 2023

Drug–drug interactions (DDIs) involving hepatic organic anion transporting polypeptides 1B1/1B3 (OATP1B) can be substantial, however, challenges remain for predicting interaction risk. Emerging evidence suggests that endogenous biomarkers, particularly coproporphyrin‐I (CP‐I), can be used to assess in vivo OATP1B activity. The present work under the International Consortium for Innovation and Quality in Pharmaceutical Development was aimed primarily at assessing CP‐I as a biomarker for informing OATP1B DDI risk. Literature and unpublished CP‐I data along with pertinent in vitro and clinical DDI information were collected to identify DDIs primarily involving OATP1B inhibition and assess the relationship between OATP1B substrate drug and CP‐I exposure changes. Static models to predict changes in exposure of CP‐I, as a selective OATP1B substrate, were also evaluated. Significant correlations were observed between CP‐I area under the curve ratio (AUCR) or maximum concentration ratio (CmaxR) and AUCR of substrate drugs. In general, the CP‐I CmaxR was equal to or greater than the CP‐I AUCR. CP‐I CmaxR < 1.25 was associated with absence of OATP1B‐mediated DDIs (AUCR < 1.25) with no false negative predictions. CP‐I CmaxR < 2 was associated with weak OATP1B‐mediated DDIs (AUCR < 2). A correlation was identified between CP‐I exposure changes and OATP1B1 static DDI predictions. Recommendations for collecting and interpreting CP‐I data are discussed, including a decision tree for guiding DDI risk assessment. In conclusion, measurement of CP‐I is recommended to inform OATP1B inhibition potential. The current analysis identified changes in CP‐I exposure that may be used to prioritize, delay, or replace clinical DDI studies.
K2S2O8‐Mediated C‐3 Formylation of Imidazopyridines Using Glyoxylic Acid
Authors: Indurthi Harish K. , Das Samarpita , Saha Pallavi , Sharma Deepak K.
Published: September 2023

A metal‐free formylation of imidazopyridines by direct decarboxylative cross‐coupling of glyoxylic acid in presence of K2S2O8 as oxidant under mild and neutral conditions is described. This reaction features a broad substrate scope, good functional group tolerance, and generates products in good yields between 68–85 %. The translational capacity of the reaction from a laboratory methodology to gram‐scale synthesis has also been ensured. The involvement of a radical pathway has been demonstrated by radical trapping experiments with 2,2,6,6‐tetramethylpiperidine‐1‐oxyl (TEMPO) and 2,6‐di‐tert‐butyl‐4‐methylphenol (BHT).
Dual‐laser pulse‐patterned α‐Co(OH)2/rGO heterointerface for accelerated water oxidation and surface phase‐transition via in‐situ Raman spectroscopy
Authors: Lee Yeryeong , Theerthagiri Jayaraman , Min Ahreum , Moon Cheol Joo , Choi Myong Yong
Published: September 2023

The dynamic surface reconstruction of electrodes is a legible sign to understand the deep phase‐transition mechanistic and electrocatalytic origin during the oxygen evolution reaction (OER). Herein, we report a dual‐laser pulse‐patterned heterointerface of α‐Co(OH)2 and reduced graphene oxide (rGO) nanosheets via pulsed laser irradiation in liquid (PLIL) to accelerate OER kinetics. α‐Co(OH)2 was formed from the OH− ions generated during the PLIL of GO at neutral pH. Co2+ modulation in tetrahedral coordination sites benefits as an electrophilic surface for water oxidation. Few d‐vacancies in Co2+ increase its affinity toward oxygen, lowering the energy barrier and generating many CoOOH and CoO2 active sites. rGO with an ordered π‐conjugated system aids the surface adsorption of OOH*, O*, and OH* during OER. α‐Co(OH)2 surface phase‐transition and OER mechanistic steps occurred via phase‐reconstruction to CoOOH and CoO2 reactive intermediates, uncovered using in situ electrochemical–Raman spectroscopy. Our findings in the dual‐laser pulse strategy and the surface reconstruction correlation in active OER catalysts pave the path for paramount in multiple energy technologies.

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A novel Woodbury solution method for nonlinear seismic response analysis of large‐scale structures
Authors: Yu Ding‐Hao , Li Gang
Published: September 2023

The Woodbury formula is an efficient tool in mathematics to calculate low‐rank perturbation problems and has been applied to improve the computational efficiency of nonlinear seismic response analysis (NSRA) of structures with local nonlinearity. Using the Woodbury formula for NSRA can avoid the time‐consuming recalculation and factorization of the large‐dimensional global stiffness matrix of a structure by only solving a small‐dimensional Schur complement system representing local nonlinearity per iteration. Because the dimension of the Schur complement matrix is determined by the inelastic degree of freedom (IDOF) number, which represents the scale of local nonlinear regions, a small IDOF number is helpful for achieving the high‐efficiency advantage of the Woodbury formula. However, when performing NSRA for large‐scale structures, the IDOF number is usually relatively large, which contradicts the efficiency requirement of the Woodbury formula. To solve this problem and extend the advantage of the Woodbury formula to the NSRA of large‐scale structures, this paper first proposes a two‐stage IDOF number reduction method by eliminating the IDOFs that have insignificant effects on the results, and consequently, a variant Woodbury formula is derived. Because only the principal component in the Schur complement matrix is retained, the dimension of this matrix and the cost for factorizing it can be reduced significantly without losing accuracy, thus greatly improving the efficiency of the proposed method. Moreover, to reduce the additional computational time introduced by the IDOF number reduction procedure and to further improve the computational performance of the proposed method, an OpenMP parallel computational strategy is incorporated. Finally, the validity of the proposed method is verified by implementing incremental dynamic analysis for a large‐scale reinforced concrete structure.
A critical analysis of India's pre‐pack regime for MSMEs
Authors: Tripathi Urmika
Published: September 2023

Hybrid restructuring procedures, such as pre‐packs, have been encouraged to deal with an expected increase in insolvent firms in the aftermath of the COVID‐19 pandemic. Pre‐packs have been gaining popularity as a restructuring mechanism across the world. India too introduced a pre‐packaged insolvency resolution process for micro, small and medium enterprises (MSMEs) in April 2021. This article first provides a brief overview of the pre‐pack models employed in certain other jurisdictions such as the United States of America, United Kingdom and Singapore with a view to understanding the key features of pre‐pack models and how they have been operationalised in these jurisdictions. It then briefly discusses other restructuring avenues, that were available to a corporate debtor in India, and the circumstances that led up to the introduction of pre‐packs in India. Finally, it provides a detailed overview of the Indian pre‐pack regime and evaluates its effectiveness for MSMEs, potential issues that may cause delays in the process and how the current pre‐pack regime can be further streamlined. It argues that some of the procedural requirements and features of the Indian pre‐pack regime may not be suitable for MSME insolvencies.
Purification and Characterization of a Lipophilic Factor From Testicular Macrophages That Stimulates Testosterone Production by Leydig Cells
Authors: HUTSON JAMES C. , GARNER CHARLES W. , DORIS PETER A.
Published: September 2023

ABSTRACT:Testicular macrophages have been shown to secrete a factor that stimulates testosterone production by Leydig cells. The purpose of this investigation was to purify and characterize this factor. Medium was collected from 24‐ to 48‐hour cultures of testicular macrophages isolated from adult rats. This medium induced a sevenfold increase in testosterone production by cultured Leydig cells. When the medium was extracted with ether, all biological activity was found in the organic phase, indicating that the factor was lipophilic. The ether extract was then fractionated on a C18reversed‐phase high‐performance liquid chromatography (HPLC) column, using a gradient of acidified methanol as the mobile phase. Leydig cell‐stimulating activity eluted at approximately 11 minutes. Standards of testosterone, dihydroepiandrosterone (DHEA), pregnenolone, progesterone, dihydrotestosterone (DHT), and prostaglandin E2(PGE2) all had elution times of between 5 and 6 minutes, under identical column conditions. The biological activity of the HPLC‐purified fraction was partly resistant to boiling but was completely abolished by Dextran‐coated charcoal treatment. Biological activity of testicular macrophage‐conditioned medium was not abolished following chymotrypsin treatment, indicating that this molecule was not a hydrophilic peptide. It was found that the factor obtained by reversed‐phase HPLC could be further purified by normal‐phase HPLC. The results of this investigation demonstrate that the testicular macrophage‐derived factor that stimulates testosterone production by Ley‐dig cells can be purified by organic extraction and HPLC, and that it is a highly potent chymotrypsin‐resistant heat‐stable lipophilic factor.
Effect of Finasteride on Human Testicular Steroidogenesis
Authors: CASTRO‐MAGANA MARIANO , ANGULO MORIS , FUENTES BILLY , CANAS ATILIO , SARRANTONIO MARY , ARGUELLO RAUL , VITOLLO PAM
Published: September 2023

ABSTRACT: We studied the testicular function and some androgen‐mediated events in 22 males (16–30 years of age) with male pattern baldness that was treated with finasteride (10 mg once daily) for 2 years. Patients were evaluated every 3 months. Prostatic volume was determined in six subjects by endorectal ultrasound scans. Serum gonadotropin, prostate‐specific antigen (PSA), and sex hormone levels were determined basally and periodically during the treatment period. Fourteen subjects underwent gonadal stimulation with human chorionic gonadotropin (hCG), and the gonadotropin response to gonadotropin releasing hormone (GnRH) was determined in eight subjects, prior to and after 2 years of therapy. Finasteride treatment resulted in an improvement in the male pattern baldness and prostatic shrinkage that was associated with an increase in serum testosterone levels (17.2 ± 2.5 vs. 26.3 ± 1.7 nmol/L) and a decrease in dihydrotestosterone (DHT) levels (1.45 ± 0.41 vs. 0.38 ± 0.10 nmol/L), causing a marked increase in that testosterone /DHT ratio. A significant increase in the serum levels of androstenedione (3.67 ± 0.49 vs. 7.05 ± 0.70 nmol/L) and estradiol (132 ± 44 vs. 187 ± 26 pmol/L) was also noted, whereas androstanediol glucoronide (33.3 ± 6.4 vs. 10.7 ± 4.5 pmol) and PSA (1.6 ± 0.6 vs. 0.4 ± 0.1 ng/ml) were significantly decreased. No changes in basal or stimulated levels of gonadotropin were observed. There was a significant increase in the testosterone response to hCG during finasteride therapy (Δ: 16.7 vs. 35.5 nmol/L) that could be explained, at least in part, by the reduction of testosterone metabolism resulting from the blockage induced by finasteride. The decrease in the androstenedione to testosterone and estrone to estradiol ratios observed after hCG treatment, however, strongly suggests increased activity of the 17‐ketosteroid reductase enzyme and an improvement of the testicular capacity for testosterone production.
Anti‐Bull Sperm Monoclonal Antibodies: II. Binding Changes During Capacitation and Influence on Sperm‐Zona Interactions In Vitro
Authors: Ambrose J. Divakar , Rajamahendran Rajadurai , Lee C. Y. Gregory
Published: September 2023

ABSTRACT: Anti‐bull sperm monoclonal antibodies (mAbs), generated against intra‐acrosomal and surface antigens, were evaluated for their functional significance. In experiment I, the influence of mAbs on the bovine sperm—oocyte interaction in vitro was tested on a total of 493 oocytes in either three or four replicate trials. Although the number of sperm bound per zona increased significantly over untreated control samples (23.6 ± 5.6 vs. 10.0 + 2.4, mean ± standard error [SE]; P < 0.001) in the presence of one surface‐reacting mAb, other mAbs had no effect. Experiment II was designed to determine if the mAbs would detect capacitation‐related changes of bull sperm in vitro. Bull sperm were incubated in capacitation medium (supplemented Tyrode's medium [TALP] plus 10 μg/ml heparin) for up to 4.5 hours. At 0 and at 4 hours, mAbs in hybridoma culture supernatant were incubated for 30 minutes with sperm, labeled with fluorescein isothiocyanate (FITC)‐conjugated secondary antibody, and processed for indirect immunofluorescence assay. Four mAbs specific to intra‐acrosomal antigens exhibited a time‐dependent increase (P < 0.05) in binding to bull sperm incubated under capacitation conditions. In contrast, the binding of the mAbs specific to surface antigens significantly decreased (P < 0.05) after 4 hours in the presence of heparin. Sperm viability did not change during the 4‐hour period. In experiment III, mAbs specific to intra‐acrosomal antigens were evaluated to assess bull sperm acrosomal status following lysophosphatidylcholine‐induced acrosome reaction. A significant decrease (P < 0.01) in mAb binding following the induced acrosome reaction was observed with all the mAbs; it was highly correlated (r ≥ 0.85; P < 0.01) with Pisum sativum agglutinin binding and Giemsa staining. The results suggest that some of the mAbs are potential biological markers for bull sperm surface changes associated with capacitation and the acrosome reaction in vitro.
DeepHistoNet: A robust deep‐learning model for the classification of hepatocellular, lung, and colon carcinoma
Authors: Kadirappa Ravindranath , S. Deivalakshmi , R. Pandeeswari , Ko Seok‐Bum
Published: September 2023

In recent days, non‐communicable diseases (NCDs) require more attention since they require specialized infrastructure for treatment. As per the cancer population registry estimate, nearly 800,000 new cancer cases will be detected yearly. The statistics alarm the need for early cancer detection and diagnosis. Cancer identification can be made either through manual efforts or by computer‐aided algorithms. Manual efforts‐based cancer detection is labor intensive and also offers more time complexity. In contrast, computer‐aided algorithms offer feasibility in reducing time and manual efforts. With the motivation to develop a computer‐aided diagnosis system for NCD, we developed a cancer detection methodology. In the present article, a deep learning (DL)‐based cancer identification model is developed. In DL‐based architectures, the features are generally extracted using convolutional neural networks. The proposed attention‐guided, densely connected residual, and dilated convolution deep neural network called DeepHistoNet acquire precise patterns for classification. Experimentation has been carried out on Kasturba Medical College (KMC), TCGA‐LIHC, and LC25000 datasets to prove the robustness of the model. Performance evaluation metrics like F1‐score, sensitivity, specificity, recall, and accuracy validate the experimentation. Experimental results demonstrate that the proposed DeepHistoNet model outperforms the other state‐of‐the‐art methods. The proposed model has been able to classify the KMC liver dataset with 97.1% accuracy and 0.9867 value of area under the curve–receiver operating characteristic curve (AUC‐ROC), which is the best result obtained compared to the state‐of‐the‐art techniques. The performance of the DeepHistoNet has been even better on the LC25000 dataset. On the LC25000 dataset, the proposed model achieved 99.8% classification accuracy. To our knowledge, DeepHistoNet is a novel approach for multiple histopathological image classification.

Research Highlights

A novel robust DL model is proposed for histopathological image carcinoma classification.

The precise patterns for accurate classification are extracted using dense cross‐connected residual blocks.

Spatial attention is provided to the network so that the spatial information is not lost during the feature extraction.

DeepHistoNet is trained and evaluated on the liver, lung, and colon histopathology datasets to demonstrate its resilience. The results are promising and outperform state‐of‐the‐art techniques.

The proposed methodology has obtained the AUC‐ROC value of 0.9867 with a classification accuracy of 97.1% on the KMC dataset.

The proposed DeepHistoNet has classified the LC25000 dataset with 99.8% accuracy. The results are the best obtained till date.
Raman spectroscopy for crystallochemical analysis of Mg‐rich layered silicates: Serpentine and talc
Authors: Aspiotis Stylianos , Schlüter Jochen , Hildebrandt Frank , Mihailova Boriana
Published: September 2023

A series of 10 talc (nominally MMg3TSi4O10X(OH)2) and 22 serpentine (nominally MMg3TSi2O5X(OH)4) minerals have been studied by Raman spectroscopy and electron microprobe analysis (EMPA) to establish quantitative relationships between the content of octahedrally coordinated M‐site cations and Raman peak parameters, which would allow for noninvasive material profiling. We show that in the case of talc, the position of the strong and well‐resolved peak near 360 cm−1, related to MO6 vibrations, as well as the integrated intensities of the OH‐stretching Raman signals (3600–3750 cm−1) can be used to determine the amount of MMg and M(Fe2+ + Mn2+) with a precision similar to that of EMPA. In the case of serpentine, the overall shape of the Raman scattering arising from OH‐stretching modes (3600–3750 cm−1) can be initially used to distinguish between the different polymorphs: antigorite, chrysotile, and lizardite, as well as the lizardite‐/chrysotile‐rich polygonal/polyhedral serpentine varieties and then, the full width at half maximum (FWHM) of the strongest MO6 peak at ~380 cm−1 can be used to estimate MMg content in each of the analyzed polymorphs/varieties and a relative error of 5%. In addition, MFe2+ amount in chrysotile and chrysotile‐rich polygonal serpentine can be quantified by FWHM of the peak near 230 cm−1 with a relative error of 5%, whereas MFe2+ amount in antigorite can be derived from FWHM of the peak near 130 cm−1 with similar relative uncertainties. We demonstrate the effectiveness of our approach on two types of rock‐based cultural‐heritage objects, cylinder seals and inscribed gems, where sampling is prohibitive.