bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subacute Toxicity Study of Stem Extract of Telfairia occidentalis in Rats
Authors: Andrew Ukeme Essien , Okokon Jude Efiom , Osigwe Chinyelu Clementina , Uwaeme Ugonma Florence , Isenigeri Uduak Peter 
Published: January 2025

Telfairia occidentalis Hook (Cucurbitaceae) is used in Ibibio ethnomedicine for the treatment of diverse diseases such as malaria, diabetes and gastrointestinal disorders. Evaluation of subacute administration of ethanol stem extract of Telfaira occidentalis for effect on hematological indices, liver and kidney functions as well as lipid profile of rats was carried out. The stem extract (200, 400, 600 mg/kg body weight) was orally administered to Wistar rats daily for 30 days and the rats were sacrificed under light diethyl ether anesthesia at the completion of the administration. Subacute administration of T. occidentalis stem extract resulted in insignificant increase in body weights of rats especially at high doses without any significant (p>0.05) effect on the weights of heart, brain, liver, kidney, spleen and testes when compared to control, but the weights of ovary was decreased significantly (p<0.01) at higher doses (400 and 600 mg/kg) relative to control. The stem extract treatment did not affect the WBC, RBC and platelets counts, hemoglobin concentration, lymphocytes, monocytes, eosinophil and basophil percentages as well as bleeding and clotting times significantly (p>0.05) relative to control. However, significant (p<0.05) increase of neutrophils percentage at low dose (200 mg/kg) and decreased PCV percentage at higher doses (400 and 600 mg/kg) when compared to control were recorded. The stem extract administration did not cause any significant (p>0.05) effect on total protein, albumin, ALP, total and conjugated bilirubin levels of rats except significantly (p<0.05-0.01) elevated ALT and AST levels at low dose (200 mg/kg) of the extract when compared to control. The stem extract did not cause any significant effect (p>0.05) on creatinine, potassium, sodium, chloride and bicarbonate levels of the treated rats except significantly (p<0.001) elevated urea level at low dose of the extract (200 mg/kg), but caused dose-dependent and insignificant (p>0.05) decreases in total cholesterol, triglyceride, HDL, LDL and VLDL levels when compared to control. The stem extract exerted mild to moderate effect on the histologies of brain, heart, spleen, livers, kidneys, testes and a severe effect on ovaries of rats. Chronic study is advocated to investigate the effect of prolonged administration of the stem extract organs and systems of rats.
Overall Survival After Treatment Failure Among Patients With Rectal Cancer
Authors: Diefenhardt Markus , Martin Daniel , Fleischmann Maximilian , Hofheinz Ralf-Dieter , Ghadimi Michael , Rödel Claus , Fokas Emmanouil 
Published: October 2023

ImportanceOncologic outcomes among patients with rectal cancer after developing local recurrence and/or distant metastases remain poorly studied.ObjectiveTo analyze the trend of overall survival after treatment failure for patients with rectal cancer within three consecutive phase 2 or 3 trials of the German Rectal Cancer Study Group.Design, Setting, and ParticipantsThis cohort study is a post hoc analysis of 3 randomized phase 2 or 3 trials (CAO/ARO/AIO-94, -04, and -12 trials, conducted in Germany) that included 1948 patients with locally advanced rectal adenocarcinoma. The CAO/ARO/AIO-94 trial recruited patients between February 1995 and September 2002, the CAO/ARO/AIO-04 trial recruited patients between July 2006 and February 2010, and the CAO/ARO/AIO-12 trial recruited patients between June 2015 and January 2018. Statistical analysis was conducted between September 2022 and March 2023.ExposuresA total of 119 of 391 patients in the CAO/ARO/AIO-94 trial group A, 295 of 1236 patients in the CAO/ARO/AIO-04 trial, and 69 of 306 in the CAO/ARO/AIO-12 trial experienced treatment failure (R2 resection or local recurrence or distant metastases) and were included in further analyses.Main Outcomes and MeasuresCharacteristics of treatment failure and overall survival were assessed in all 3 trial cohorts.ResultsOf the 1948 patients treated in the 3 trials, 15 were excluded because of missing data. Of the remaining 1933 patients (median age, 62.5 years [range, 19-84 years]; 1363 men [71%] and 570 women [29%]) with locally advanced rectal adenocarcinoma (cT3 or 4 or cN+) treated within 3 consecutive clinical trials, 483 experienced treatment failure and were analyzed. After a median follow-up of 36 months (IQR, 24-51 months) for all patients, overall survival after treatment failure was significantly improved in the CAO/ARO/AIO-04 trial (at 3 years, 44% [IQR, 37%-51%]; hazard ratio [HR], 0.61 [95% CI, 0.47-0.79]) and further improved in the CAO/ARO/AIO-12 trial (at 3 years, 73% [IQR, 60%-87%]; HR, 0.32 [95% CI, 0.18-0.54]) compared with the CAO/ARO/AIO-94 trial (at 3 years, 30% [IQR, 22%-39%]) (both P &amp;lt; .001). Distant metastasis was the main reason for treatment failure throughout a 5-year follow-up (range, 67%-87%), and the relative risk for treatment failure was highest in the first 18 months in all 3 trials. ypTNM stage was significantly associated with the risk and time interval to treatment failure. Improvement in overall survival after treatment failure was independent of sex.Conclusions and RelevanceThis cohort study suggests that advancements in salvage strategies during the past decades have likely improved overall survival among patients with rectal cancer who experienced treatment failure.
Development of Coulometric Mass Spectrometry for Absolute Chemical Quantitation
Authors: Ai Yongling , Joel FNU Praneeth Ivan , Zhao Pengyi , Hassan Md Tanim‐Al , Sharma Arjun , Hao Gracelynne , Zhou Zhenghao , Chen Hao 
Published: October 2023

AbstractIn the past decades,mass spectrometry(MS)‐based absolute quantitation has become a powerful tool to facilitate advancement in both biomedical and clinical fields. The main advantage of MS‐based quantitation is the accurate and simultaneous quantitation of multiple analytes with high sensitivity. However, a reference material (e.g. authentic target analytes or isotope‐labeled peptide standards) is indispensable for those quantitation methods to build a calibration curve for each analyte, which might not be available or difficult to synthesize especially for some drug molecules with complicated structure or proteins/peptides withpost‐translational modifications (PTMs). To tackle this issue, our group recently developed a standard‐free absolute quantitation approach based on the combination ofelectrochemistry(EC) and MS, involving the coulometric measurement of analyte oxidation/reduction current as well as mass spectrometric measurement of the redox reaction yield. We named the method ascoulometric mass spectrometry(CMS). Although the combined EC/MS technique is a quickly growing research field in analytical chemistry with numerous distinct applications, the quantitation‐centered application has not been systematically reported. In this review, the principle, apparatus, and various applications of this emerging EC/MS hybrid quantitation method are presented and discussed in detail. An overview of the capabilities of CMS for absolute quantitation across a variety of modalities including small molecule metabolites, peptides, proteins, large molecule biotherapeutics, and PTMs as well as the role of CMS for drug impurity quantitation is provided. Simultaneously, the limitations of the method, which need further optimization and improvement, as well as promising future applications in drug development and proteomics are presented and evaluated.
Deep Learning for Size‐Agnostic Inverse Design of Random‐Network 3D Printed Mechanical Metamaterials
Authors: Pahlavani Helda , Tsifoutis‐Kazolis Kostas , Saldivar Mauricio C. , Mody Prerak , Zhou Jie , Mirzaali Mohammad J. , Zadpoor Amir A. 
Published: October 2023

AbstractPractical applications of mechanical metamaterials often involve solving inverse problems aimed at finding microarchitectures that give rise to certain properties. The limited resolution of additive manufacturing techniques often requires solving such inverse problems for specific specimen sizes. Moreover, the candidate microarchitectures should be resistant to fatigue and fracture. Such a multi‐objective inverse design problem is formidably difficult to solve but its solution is the key to real‐world applications of mechanical metamaterials. Here, a modular approach titled “Deep‐DRAM” that combines four decoupled models is proposed, including two deep learning (DL) models, a deep generative model based on conditional variational autoencoders, and direct finite element (FE) simulations. Deep‐DRAM integrates these models into a framework capable of finding many solutions to the posed multi‐objective inverse design problem based on random‐network unit cells. Using an extensive set of simulations as well as experiments performed on 3D printed specimens, it is demonstrate that: 1) the predictions of the DL models are in agreement with FE simulations and experimental observations, 2) an enlarged envelope of achievable elastic properties (e.g., rare combinations of double auxeticity and high stiffness) is realized using the proposed approach, and 3) Deep‐DRAM can provide many solutions to the considered multi‐objective inverse design problem.
Dual‐Responsive Nanorobot‐Based Marsupial Robotic System for Intracranial Cross‐Scale Targeting Drug Delivery
Authors: Wu Junfeng , Jiao Niandong , Lin Daojing , Li Na , Ma Tianyang , Tung Steve , Cheng Wen , Wu Anhua , Liu Lianqing 
Published: October 2023

AbstractNanorobots capable of active movement are an exciting technology for targeted therapeutic intervention. However, the extensive motion range and hindrance of the blood–brain barrier impeded their clinical translation in glioblastoma therapy. Here, a marsupial robotic system constructed by integrating chemical/magnetic hybrid nanorobots (child robots) with a miniature magnetic continuum robot (mother robot) for intracranial cross‐scale targeting drug delivery is reported. For primary targeting on macroscale, the continuum robot enters the cranial cavity through a minimally invasive channel (e.g., Ommaya device) in the skull and transports the nanorobots to pathogenic regions. Upon circumventing the blood–brain barrier, the released nanorobots perform secondary targeting on microscale to further enhance the spatial resolution of drug delivery. In vitro experiments against primary glioblastoma cells derived from different patients are conducted for personalized treatment guidance. The operation feasibility within organisms is shown in ex vivo swine brain experiments. The biosafety of the treatment system is suggested in in vivo experiments. Owing to the hierarchical targeting method, the targeting rate, targeting accuracy, and treatment efficacy have improved greatly. The marsupial robotic system offers a novel intracranial local therapeutic strategy and constitutes a key milestone in the development of glioblastoma treatment platforms.
Solid‐Phase Synthesis and Biological Evaluation of Peptides ADP‐Ribosylated at Histidine
Authors: Minnee Hugo , Rack Johannes G. M. , van der Marel Gijsbert A. , Overkleeft Herman S. , Codée Jeroen D. C. , Ahel Ivan , Filippov Dmitri V. 
Published: October 2023

AbstractThe transfer of an adenosine diphosphate (ADP) ribose moiety to a nucleophilic side chain by consumption of nicotinamide adenine dinucleotide is referred to as ADP‐ribosylation, which allows for the spatiotemporal regulation of vital processes such as apoptosis and DNA repair. Recent mass‐spectrometry based analyses of the “ADP‐ribosylome” have identified histidine as ADP‐ribose acceptor site. In order to study this modification, a fully synthetic strategy towards α‐configured N(τ)‐ and N(π)‐ADP‐ribosylated histidine‐containing peptides has been developed. Ribofuranosylated histidine building blocks were obtained via Mukaiyama‐type glycosylation and the building blocks were integrated into an ADP‐ribosylome derived peptide sequence using fluorenylmethyloxycarbonyl (Fmoc)‐based solid‐phase peptide synthesis. On‐resin installation of the ADP moiety was achieved using phosphoramidite chemistry, and global deprotection provided the desired ADP‐ribosylated oligopeptides. The stability under various chemical conditions and resistance against (ADP‐ribosyl) hydrolase‐mediated degradation has been investigated to reveal that the constructs are stable under various chemical conditions and non‐degradable by any of the known ADP‐ribosylhydrolases.
Synthesis and biological evaluation of novel salicylidene uracils: Cytotoxic activity on human cancer cell lines and inhibitory action on enzymatic activity
Authors: Poslu Ayşe Halıç , Aslan Şafak Esra , Koz Gamze , Senturk Esra , Koz Ömer , Senturk Murat , Nalbantsoy Ayşe , Öztekin Aykut , Ekinci Deniz 
Published: October 2023

AbstractA series of salicylidene uracil (1–18) derived from 5‐aminouracil and substituted salicylaldehydes were analyzed for cytotoxic activity and enzyme inhibitory potency. Nine out of eighteen derivatives (6–8, 10, 12–15, 18) are novel molecules synthesized for the first time in this work, and other derivatives were previously synthesized by our group. The compounds were characterized by Proton nuclear magnetic resonance, carbon nuclear magnetic resonance, fourier transform infrared spectroscopy, and elemental analysis. All compounds were tested for their in vitro cytotoxicity against PC‐3 (human prostate adenocarcinoma), A549 (human alveolar adenocarcinoma), and SHSY‐5Y (human neuroblastoma) cancer cell lines and the nontumorigenic HEK293 (human embryonic kidney cells) cell line. The 3,5‐di‐tert‐butylsalicylaldehyde derived compound (8) was toxic to PC‐3 human prostate adenocarcinoma cells, showing a promising IC50 value at 7.05 ± 0.76 μM. The present study also aimed to evaluate the inhibitory effects of the compounds against several key enzymes, namely carbonic anhydrase I and II (CA I and CA II), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and glutathione reductase (GR), which are implicated in various global disorders, such as Alzheimer's disease, epilepsy, cancer, malaria, diabetes, and glaucoma. The inhibitory profiles of the tested compounds were assessed by determining their Ki values, which ranged from 2.96 to 9.24 nM for AChE, 3.78 to 12.57 nM for BChE, 8.42 to 25.74 nM for CA I, 7.24 to 19.74 nM for CA II, and 0.541 to 1.124 μM for GR. Molecular docking studies were also performed for all compounds. Most derivatives exhibited much more effective inhibitory action compared with clinically used standards. Thus, our findings indicate that the salicylidene derivatives presented in this study are promising drug candidates that need further evaluation.
Recombinant adeno‐associated virus production evaluation in Chinese hamster ovary cells
Authors: Cao Thu M. , Chen Dayue , Barnard Gavin C. , Shen Amy 
Published: October 2023

AbstractThe gene therapy field has advanced in recent years with five recombinant adeno‐associated virus (rAAV) based products winning Food and Drug Administration (FDA) approval. As the number of therapeutic applications and overall production demands for rAAV increase, it is valuable to evaluate rAAV production in different production cells. Chinese hamster ovary (CHO) cells have been a robust host for biomolecule manufacturing for more than 35 years. However, there is no report to our knowledge describing the use of CHO cells for rAAV production. In this study, we examined the ability of CHO cells to produce rAAV using a transient plasmid transfection approach. Our results demonstrated that CHO is capable of producing rAAV with detectable viral fundamental components including viral RNAs, proteins, and rAAV viral particles. We identified the expression of cap proteins as one of the limiting factors for rAAV production in CHO cells. We therefore added an additional cytomegalovirus (CMV)‐Cap plasmid to the CHO transfection. After increasing cap protein expression, we detected rAAV titers as high as 3 × 108 viral genomes for every 2 × 109 capsids in CHO cells using a quintuple transfection method (standard AAV2 Rep/Cap, helper, gene of interest plasmids, plus CMV‐E1, and CMV‐Cap plasmids) with comparable full particle percent (average 15%) to that of human embryo kidney (HEK)‐derived rAAV. Our study provides a foundation for potential rAAV production in CHO cells.
Association between baseline blood pressure and the incidence of lenvatinib‐induced hypertension in patients with thyroid cancer
Authors: Shibutani Yuma , Tajiri Kazuko , Suzuki Shinya , Enokida Tomohiro , Sagara Atsunobu , Okano Susumu , Fujisawa Takao , Sato Fumiaki , Yumoto Tetsuro , Sano Motohiko , Kawasaki Toshikatsu , Tahara Makoto 
Published: October 2023

AbstractBackgroundHypertension is the most frequently occurring adverse event of lenvatinib, recognized relatively early in its course. However, the trend in blood pressure after the initiation of lenvatinib and the outcomes with antihypertensive treatment are unclear. This study aimed to clarify the association between baseline blood pressure and the incidence of lenvatinib‐induced hypertension in patients with thyroid cancer.MethodsThis retrospective study included 65 patients without hypertension at the time of lenvatinib initiation. Patients were divided into two groups: those who developed hypertension grade ≥3 (HTN group) and those who did not develop hypertension grade ≥3 (non‐HTN group).ResultsOf the 65 patients, 46 (71%) developed hypertension grade ≥3. In both HTN and non‐HTN groups, blood pressure significantly increased the day after lenvatinib initiation. There was no significant difference in the elevated values of both the changes in systolic blood pressure (ΔSBP) and diastolic blood pressure (ΔDBP) between the two groups, with an average increase of 20 mmHg in SBP and 13 mmHg in DBP from baseline. The median (range) time to the onset of hypertension grade ≥3 was 2 days (1–12 days). In the multivariable analysis, patients with normal (SBP 120–129 mmHg and/or DBP 80–84 mmHg) or high‐normal baseline blood pressure (SBP 130–139 mmHg and/or DBP 85–89 mmHg) were at higher risk of developing hypertension grade ≥3 than those with optimal baseline blood pressure (SBP <120 mmHg and DBP <80 mmHg) (odds ratio [OR], 5.07; 95% confidential interval [CI] 1.09–23.54 and OR, 7.48; 95% CI, 1.67–33.51, respectively).ConclusionsLenvatinib‐induced hypertension appears the day after administration, and higher baseline blood pressure is a significant risk factor for developing hypertension grade ≥3. In cases of increased blood pressure with lenvatinib, early initiation of antihypertensives may prevent treatment interruption due to hypertension and maintain the therapeutic intensity of lenvatinib.
A retrospective study of sentinel lymph node biopsy for skin cancer in Japan: Comparison with breast cancer and evaluation of factors related to its use
Authors: Wada Shogo , Watanabe Tomone , Ishii Taisuke , Ichinose Yuichi , Rikitake Ryoko , Ogata Dai , Nakano Eiji , Namikawa Kenjiro , Yamazaki Naoya , Higashi Takahiro 
Published: October 2023

AbstractBackgroundSentinel lymph node biopsy (SLNB) underuse has been reported for skin cancers; however, actual performance rates have not been compared. The objective of this study was to investigate the SLNB performance rate in skin cancers covered by health insurance in Japan and compare it with that in breast cancer.MethodsThis was a retrospective study of the SLNB performance rate in SLNB‐eligible patients with breast or skin cancer from 2018 to 2019, utilizing a database linked to the Hospital‐Based Cancer Registry and Diagnosis Procedure Combination survey. Demographic and tumor characteristics were analyzed using logistic regression.ResultsA total of 71,652 patients were included in this study. SLNB was performed in 86.4% (57,904/67,036) of the patients with breast cancer, 44.7% (694/1552) with melanomas, 3.1% (89/2849) with squamous cell carcinomas (SCCs), and 13.5% (29/215) with Merkel cell carcinomas (MCCs). The performance rate of SLNB was significantly lower for skin cancers than for breast cancers (odds ratio [OR], 0.03; p < 0.001). In addition, the performance rates of SLNB were significantly lower for SCCs and MCCs than for melanomas (SCC: OR, 0.04; p < 0.001; MCC: OR, 0.19; p < 0.001). Factors associated with SLNB performance included age, sex, year of incidence, primary tumor site, T stage, and number of hospital beds.ConclusionsSLNB is underutilized for skin cancer. Further investigation is required to explore the reasons for its underutilization so that it may be implemented more universally.
The development of the Cognitive Behavioural Social Competence Therapeutic Intervention for Adults with Autism: A mixed methods report
Authors: Tate David , Dubrow‐Marshall Linda , Allely Clare S. 
Published: October 2023

AbstractBackgroundMany young people with autism can have an average or above average IQ, yet they still struggle with the social competencies needed to successfully navigate into adulthood. Despite many individuals with autism experiencing significant challenges during their transition into adulthood, evidence‐based therapeutic interventions to support individuals with autism during this transition are limited. The current literature suggests that cognitive behavioural therapy interventions can help improve social skills and the mental health of individuals with autism. However, little is known about the benefits for young adults with autism transitioning or who have transitioned into adulthood.Aims and MethodThe aim of this research was to deliver a newly developed Cognitive Behavioural Social Competence Therapeutic Intervention for Adults with Autism (CBSCTI‐A) to five young adults with autism. Research aims were to evaluate intervention feasibility and efficacy by triangulating data findings using a mixed methods approach.ResultsResults support feasibility, with CBSCTI‐A receiving very high user satisfaction ratings, and adherence to the intervention was high, recorded at ~90%. Fidelity to treatment was also high, ranging from ~86% to ~100%. Quantitative findings indicate that over an eight‐week time period, a small sample of young adults with autism experienced significant improvements with regard to their social motivation, non‐verbal conversation, emotional empathy, assertiveness, interpersonal relationships and self‐control. Qualitative findings provide further anecdotal support for intervention feasibility and efficacy. After the completion of the intervention, participants and their parents were invited to complete semistructured interviews. Thematic analysis (TA) revealed four main themes: user satisfaction, important components of therapeutic intervention, challenges and critiques, and recommendations.ConclusionsCBSCTI‐A appears to be a feasible intervention; however, future research with larger samples and more rigorous controlled trials is needed before efficacy can be established.
Fe‐catalyzed Selective N‐Formylation Protocol for Amines Using Glycolic Acid as C1 Bio‐Building Block
Authors: Gokhale Tejas A. , Jagtap Prafull A. , Bhanage Bhalchandra M. 
Published: October 2023

AbstractDue to current global issues involving climate change and energy crises, it requires several complete overhauls in process developments sectors of energy and chemical manufacturing industries towards more sustainable and readily applicable protocols. As a contribution to this goal with an example of iron‐based catalysis, this work presents a synthetic protocol for synthesis of N‐formamides with glycolic acid as a C1 bio‐building block, which is catalyzed through earth abundant and magnetically active Fe powder as catalyst. The protocol was applied to a wide variety of substrates affording yields in the range of 68–94 % and also performed well at 1 gram and 5 gram scale with yields of up to 86 % and 83 %, respectively. The catalyst was shown to be reusable up to 4 runs and the spent catalyst has been studied using PXRD and XPS analyses to determine catalyst deactivation and its remediation. Plausible reaction pathway has been suggested based on control experiments and GC‐MS results for the process.