bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of PD‐L1 tumor proportion score ≥20% with early resistance to osimertinib in patients with EGFR‐mutated NSCLC
Authors: Hamakawa Yusuke , Agemi Yoko , Shiba Aya , Ikeda Toshiki , Higashi Yuko , Aga Masaharu , Miyazaki Kazuhito , Taniguchi Yuri , Misumi Yuki , Nakamura Yukiko , Shimokawa Tsuneo , Saigusa Yusuke , Kobayashi Nobuaki , Okamoto Hiroaki , Kaneko Takeshi
Published: August 2023

Background

The relationship between epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI) resistance, including osimertinib, and programmed cell death‐ligand 1 (PD‐L1) expression status in EGFR‐mutated non‐small cell lung carcinoma (NSCLC) remains unclear.

Patients and Methods

We retrospectively analyzed 64 patients with unresectable advanced or metastatic NSCLC carrying EGFR exon 19 deletions (ex19del) or EGFR exon 21 L858R substitutions (L858R) who received osimertinib as the first‐line treatment. We compared progression‐free survival (PFS) between eligible patients with PD‐L1 tumor proportion scores (TPS) ≥20% and PD‐L1 TPS <20% using the Kaplan–Meier survival plots with a log‐rank test. Multivariate analysis was performed to examine the poor prognostic factors of PFS.

Results

The PD‐L1 TPS ≥20% group included 22 cases (median [range] age: 70.5 [33–86] years; 10 women [45.5%]; 11 current or ex‐smokers [50%]); ECOG performance status (PS) of 0–1/2/3/4 was noted in 16/4/1/1 patients, respectively. The PD‐L1 TPS <20% group included 42 patients (median [range] age 73 [43–88] years; 29 women [69%]; 12 current or ex‐smokers [28.6%]); ECOG PS of 0–1/2/3/4 was noted in 33/6/3/0 cases, respectively. The median PFS was 9.1 and 28.1 months in the PD‐L1 TPS ≥20% and PD‐L1 TPS <20% groups, respectively (log‐rank p = 0.013). Multivariate analysis revealed that PD‐L1 TPS ≥20% was associated with PFS (hazard ratio: 2.35, 95% confidence interval: 1.09–5.08, p = 0.030).

Conclusion

PD‐L1 TPS ≥20% in patients with EGFR‐mutated NSCLC may be associated with early resistance to osimertinib.
Aging characteristics of colorectal cancer based on gut microbiota
Authors: Wu Yinhang , Zhuang Jing , Zhang Qi , Zhao Xingming , Chen Gong , Han Shugao , Hu Boyang , Wu Wei , Han Shuwen
Published: August 2023

Background

Aging is one of the factors leading to cancer. Gut microbiota is related to aging and colorectal cancer (CRC).

Methods

A total of 11 metagenomic data sets related to CRC were collected from the R package curated Metagenomic Data. After batch effect correction, healthy individuals and CRC samples were divided into three age groups. Ggplot2 and Microbiota Process packages were used for visual description of species composition and PCA in healthy individuals and CRC samples. LEfSe analysis was performed for species relative abundance data in healthy/CRC groups according to age. Spearman correlation coefficient of age‐differentiated bacteria in healthy individuals and CRC samples was calculated separately. Finally, the age prediction model and CRC risk prediction model were constructed based on the age‐differentiated bacteria.

Results

The structure and composition of the gut microbiota were significantly different among the three groups. For example, the abundance of Bacteroides vulgatus in the old group was lower than that in the other two groups, the abundance of Bacteroides fragilis increased with aging. In addition, seven species of bacteria whose abundance increases with aging were screened out. Furthermore, the abundance of pathogenic bacteria (Escherichia_coli, Butyricimonas_virosa, Ruminococcus_bicirculans, Bacteroides_fragilis and Streptococcus_vestibularis) increased with aging in CRCs. The abundance of probiotics (Eubacterium_eligens) decreased with aging in CRCs. The age prediction model for healthy individuals based on the 80 age‐related differential bacteria and model of CRC patients based on the 58 age‐related differential bacteria performed well, with AUC of 0.79 and 0.71, respectively. The AUC of CRC risk prediction model based on 45 disease differential bacteria was 0.83. After removing the intersection between the disease‐differentiated bacteria and the age‐differentiated bacteria from the healthy samples, the AUC of CRC risk prediction model based on remaining 31 bacteria was 0.8. CRC risk prediction models for each of the three age groups showed no significant difference in accuracy (young: AUC=0.82, middle: AUC=0.83, old: AUC=0.85).

Conclusion

Age as a factor affecting microbial composition should be considered in the application of gut microbiota to predict the risk of CRC.
Anticancer Potential of the Plant‐Derived Saponin Gracillin: A Comprehensive Review of Mechanistic Approaches
Authors: Bhuia Md. Shimul , Chowdhury Raihan , Sonia Fatema Akter , Kamli Hossam , Shaikh Ahmad , El‐Nashar Heba A. S. , El‐Shazly Mohamed , Islam Muhammad Torequl
Published: August 2023

With the increasing prevalence of cancer and the toxic side effects of synthetic drugs, natural products are being developed as promising therapeutic approaches. Gracillin is a naturally occurring triterpenoid steroidal saponin with several therapeutic activities. It is obtained as a major compound from different Dioscorea species. This review was designated to summarize the research progress on the anti‐cancer activities of gracillin focusing on the underlying cellular and molecular mechanisms, as well as its pharmacokinetic features. The data were collected (up to date as of May 1, 2023) from various reliable and authentic literatures comprising PubMed, Springer Link, Scopus, Wiley Online, Web of Science, ScienceDirect, and Google Scholar. The findings demonstrated that gracillin displays promising anticancer effects through various molecular mechanisms, including anti‐inflammatory effects, apoptotic cell death, induction of oxidative stress, cytotoxicity, induction of genotoxicity, cell cycle arrest, anti‐proliferative effect, autophagy, inhibition of glycolysis, and blocking of cancer cell migration. Additionally, this review highlighted the pharmacokinetic features of gracillin, indicating its lower oral bioavailability. As a conclusion, it can be proposed that gracillin could serve as a hopeful chemotherapeutic agent. However, further extensive clinical research is recommended to establish its safety, efficacy, and therapeutic potential in cancer treatment.
Four Pairs of Neuroprotective Aryldihydronaphthalene‐Type Lignanamide Enantiomers from the Herbs of Solanum lyratum
Authors: Mi Si‐Hui , Chang Ye , Zhang Xin , Hou Jiao‐Yang , Niu Jia‐Qi , Hao Jin‐Le , Yao Guo‐Dong , Lin Bin , Huang Xiao‐Xiao , Bai Ming , Song Shao‐Jiang
Published: August 2023

Four pairs of aryldihydronaphthalene‐type lignanamide enantiomers were isolated from Solanum lyratum (Solanaceae). The enantiomeric separation was accomplished by chiral‐phase HPLC, and five undescribed compounds were elucidated. Analysis by various spectroscopy and ECD calculations, the structures of undescribed compounds were illuminated. The neuroprotective effects of all compounds were evaluated using H2O2‐induced human neuroblastoma SH‐SY5Y cells and AchE inhibition activity. Among them, compound 4 a exhibited remarkable neuroprotective effects at high concentrations of 25 and 50 μmol/L comparable to Trolox. Compound 1 a showed the highest AchE inhibition with the IC50 value of 3.06±2.40 μmol/L. Molecular docking of the three active compounds was performed and the linkage between the compounds and the active site of AchE was elucidated.
Analysis of Volatile Constituent by Hydrodistillation and Solid‐Phase Microextraction Techniques and Antimicrobial and Scolicidal Activities of Essential Oil and Soxhlet Extracts of Ulva rigida grown in Turkey
Authors: Yücel Tayyibe Beyza , Korkmaz Büşra , Cebeci Tuğba , Karaman Ülkü , Arici Yeliz Kasko , Fandakli Seda , Gül Tuba
Published: August 2023

In the present study, the volatile composition of Ulva rigida (U. rigida) was elucidated by two different methods. As a result of the identification process of volatile components using the GC/MS‐FID instrument, 31 compounds were identified by hydrodistillation (HD) method, and 15 compounds were identified by solid‐phase microextraction (SPME) method, elucidating the structure of 99.86 % and 92.65 %, respectively. The most abundant compounds in the essential oil of U. rigida were n‐hexadecanoic acid and pentadecanal, while the most abundant compound according to the SPME analysis was heptadecyne, a hydrocarbon compound. In the next step, hexane, dichloromethane, chloroform and methanol solvent extracts of U. rigida were prepared and the antimicrobial activities of the extracts and the essential oil obtained by hydro‐distillation as well as the scolicidal activities of the solvent extracts were determined. The results of the antimicrobial activity test of the essential oil showed a high level of activity against Bacillus cereus ATCC 10876 and MRSA. The highest activity was found on the microorganism of Pseudomonas aeruginosa ATCC 9027 in chloroform and methanol extracts of U. rigida. Furthermore, viability detection was performed and the scolicidal effects of the extracts on protoscoleces were assessed. The values of lethal concentration doses (LD50, LD75 and LD90) were calculated using probit analysis.
New Guaiane‐Type Sesquiterpene and Norsesquiterpene from Alisma plantago‐aquatica and Their Xanthine Oxidase Inhibitory Activity
Authors: Thanh Nguyen Thi Viet , Tung Dang Thanh , Hoang Vu Dinh , Yen Pham Hai , Tai Bui Huu
Published: August 2023

A new sesquiterpene (1) and a new norsesquiterpene (2) belonging guaiane‐type skeleton together with six known compounds (3–8) were isolated from the rhizomes of Alisma plantago‐aquatica. Their structures were determined by HR‐ESI‐MS, 1D and 2D NMR spectroscopic methods. Absolute configurations of new compounds were established by experimental and TD‐DFT computational ECD spectra. Compounds 1–8 exhibited xanthine oxidase inhibitory activity with their IC50 values in range of 9.4–66.7 μM. The sesquiterpenoids 1–5 displayed the inhibitory activity and hence they could be potential xanthine oxidase inhibitors from A. plantago‐aquatica.
ROS‐Sp1 axis is involved in thermochemotherapy‐enhanced sensitivity of pancreatic cancer cells to gemcitabine
Authors: Xi Pan , Ma Xiaojuan , Hu Fuquan , Li Liang , Liu Huijuan , Zhou Jing , Wu Wenan
Published: August 2023

Gemcitabine (GEM)‐based chemotherapy represents the first choice for locally unresectable advanced pancreatic cancer, while the benefit is limited due to acquired chemoresistance or drug delivery insufficiency. Hyperthermia treatment potentially improves the clinical efficacy of GEM. However, the underlying mechanism is incompletely revealed. Our study aims to investigate the effect and involved mechanism of thermochemotherapy on cell survival. Pancreatic cancer cells PANC‐1 and ASPC‐1 were either treated with GEM or thermochemotherapy, then cell viability, apoptosis, migration, invasion, reactive oxygen species (ROS) production, and Sp1 expression were evaluated. The results showed that GEM dose and time‐dependently affected cell viability, and 30 μM GEM achieved favorable effect in suppressing cancer cell growth. Meanwhile, hyperthermia preconditioning (43°C for 60 min) 24 h before GEM treatment yielded superior effect than other treatment sequence. GEM caused significant cell apoptosis and proapoptotic genes of both cancer cells, and thermochemotherapy further promoted apoptosis and genes transcription, accompanied by excessive ROS production. Thermochemotherapy was superior to GEM in suppressing cell migration and invasion of pancreatic cancer cells. Meanwhile, GEM significantly reduced Sp1 mRNA and protein and its downstream gene Cox‐2, and thermochemotherapy further suppressed their expressions. ROS elimination with N‐acetyl‐l‐cysteine notably neutralizes the suppressive effect of GEM and thermochemotherapy on cell growth and expressions of Sp1 and Cox‐2. In conclusion, thermochemotherapy inhibited pancreatic cell viability, migration and invasion, and promoted cell apoptosis by inducing excessive ROS production, which subsequently suppressed Sp1 expression and the downstream Cox‐2.
Influence of bran layer on rice milling quality
Authors: Oppong Siaw Michelle , McClung Anna M. , Mauromoustakos Andy , Wang Ya‐Jane
Published: August 2023

Background and Objectives

Rice milling involves applying forces to remove bran from brown rice to produce milled rice. The physical and chemical properties of a rice kernel may affect both the amount of bran removed during milling and the amount of head rice yield (HRY) produced, which is a determinant of crop value. This study investigated bran thickness and bran chemical composition as factors that influence bran removal and HRY as a result of milling.

Findings

The results showed that brown rice kernels with initial higher surface lipid contents (SLCs) required longer milling times to achieve 0.4% SLC, but the longer milling times did not translate into lower HRYs or higher bran yields. Bran chemical composition had a more significant impact on the milling characteristics than bran thickness. Arabinoxylans had the greatest impact on HRY, followed by lipids and proteins.

Conclusions

Bran thickness did not have a significant impact on the milling time, bran yield, or HRY. There was significant interaction between arabinoxylans and proteins on HRY and bran yield, which indicates the probability of crosslinking between proteins and arabinoxylans.

Significance and Novelty

This study demonstrates the importance of rice bran chemical components and their interactions in terms of rice milling quality, rather than their physical properties.
Injury to the circuit of Papez: An overlooked cause of recurrent seizures
Authors: Aker Loai , Vattoth Surjith , Paksoy Yahya
Published: August 2023

Key Clinical Message

Papez' circuit is a unique neural pathway in the limbic system that is correlated with seizure activity. Injuries affecting Papez' circuit are often small and unusual in location but can be identifiable in MRI and functional imaging modalities, which can be helpful in the workup of refractory epilepsy.

The Papez circuit is a unique neural pathway in the limbic system of the brain. We review a patient presenting with recurrent seizures as the main manifestation of Papez' circuit pathology. The radiologic features of ischemia involving the mammillothalamic tract in Papez' circuit were correlated with the seizure activity.
A series of unfortunate events: Long‐neglected malpositioned pacemaker and its consequences
Authors: Osman Abdelrahman , Ahmad Ali
Published: August 2023

Key Clinical Message

Use of pacemakers has increased in recent years, and they have become the premier treatment option for several arrhythmias. However, they are not without risk; this case report aims to show the importance of follow‐up and adherence to guidelines, and methods to diagnose a life‐threatening complication.
Type A aortic dissection during diagnostic coronary angiography in normal coronary arteries: A case report
Authors: Gonzalez Alena , Lin Xiongbin , Jaiswal Vikash , Shrestha Abhigan Babu , Song Yeonah , Song David
Published: August 2023

Key Clinical Message

Aortic dissection is one of the rare complication of coronary angiography. The main treatment underlies surgical intervention however; management should be done with patient's decision.

Coronary angiography (CA) is a widely utilized diagnostic procedure used to evaluate blood flow through the coronary arteries and detect coronary artery disease (CAD). Despite its widespread use, it has complications including non‐life‐threatening, while there are some rare complications that can occur. We present a case of an elderly woman who presented with ST elevation myocardial infarction (STEMI) and underwent CA without evidence of CAD. However, the patient later developed type A aortic dissection (AD) as a complication of the procedure. Surgery is considered emergent treatment for type A‐AD, but the patient was asymptomatic without any complaint, shared decision making was conducted and the patient decided to pursue conservative treatment without surgical intervention. Therefore, managing AD should be tailored to each patient individually through shared‐decision making.
Mediastinal emphysema around the left carotid arteries from a toothbrush impalement injury
Authors: Ueshima Manami , Kono Yusuke
Published: August 2023

This report describes a case of a pediatric patient with a fever after an oral cavity injury caused by a toothbrush. On physical examination, no bleeds or injuries in his mouth were evident, but diagnostic imaging revealed wide mediastinal emphysema including the left carotid arteries. It shows the importance of carefully examining patients not to miss life‐threating conditions.
Doppler sonography in diagnosis of Bow Hunter's syndrome
Authors: Sakaida Hiroshi , Takeuchi Kazuhiko
Published: August 2023

Bow Hunter's syndrome is a rare condition in which vertebrobasilar circulatory insufficiency develops because of neck rotation. We report a patient with Bow Hunter's syndrome diagnosed by Doppler sonography. This report demonstrates the important role of Doppler sonography in diagnosis of Bow Hunter's syndrome.
Peptide‐based Organocatalyst on Stage: Functionalizing Mesoporous Silica by Tetrazine‐Norbornene Ligation
Authors: Brand Raoul D. , Busche Steffen A. , Börner Hans G. , Smarsly Bernd M.
Published: August 2023

Organocatalysis via the enamine mechanism developed to one of the most relevant tools in carbonyl chemistry and is widely used in asymmetric organic synthesis. In this work, a strategy is presented to conveniently immobilize a peptide‐based catalyst on silica supports for use in continuous flow catalysis reactions. A set of different porous silica supports is investigated spanning from mesoporous silica particles with defined pore sizes suitable for packed bed column reactors to silica monoliths with hierarchical meso‐macropore spaces. While the silica supports are functionalized with norbornene entities, the peptide‐based organocatalyst is modified with a tetrazine moiety, enabling the immobilization via inverse electron‐demand Diels‐Alder (IEDDA) reaction. The ligation results in catalyst loadings up to 0.2 mmol g‐1, without compromising the mesopore network. The catalytic activity of the materials is proven by the asymmetric C−C coupling reaction of n‐butanal to ß‐nitrostyrene proceeding in high yield and enantioselectivity in both batch and continuous flow setups.
N/P Co‐doped Micro‐/Mesoporous Carbons Derived from Polyvinyl Pyrrolidone–Zn0.2@ZIF‐67 with Tunable Metal Valence States towards Efficient Water Splitting
Authors: Ming Yang , Wang Yidi , Hua Jiachuan , Liu Chang , Li Jiashen , Fei Bin
Published: August 2023

The enhancement of electrocatalytic water splitting by modulating the intrinsic electronic environment of active sites has recently attracted lots of interest. Herein, cobalt‐cobalt oxide (CoOx) at carbons derived from metal‐organic frameworks (Zn0.2@ZIF‐67) have been modulated by using post‐phosphine (P‐CoOx/NCs), acid leaching (Co/NCs), and oxidation (O−CoOx/NCs) treatments. With the assistance of polyvinyl pyrrolidone, the resultant carbons obtain a high surface area (645.7 m2 g−1) as well as a micro‐/mesoporous system after carbonization at 920 °C. These advantages not only enhance the catalytic performance of catalysts, but also facilitate the charge transfer between interfaces towards the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER). As a result, the constructed water splitting cell fabricated with 900P‐CoOx/NCs requires a low overpotential (89 mV and 343 mV vs. reservable hydrogen electrode respectively) to drive HER and OER at 10 mA cm−2, a low cell voltage (1.69 V), and a high stability with only 4.9 % decay after 15 hours operation in the alkaline medium.
Protein Sequencing with Artificial Intelligence: Machine Learning Integrated Phosphorene Nanoslit
Authors: Mittal Sneha , Jena Milan Kumar , Pathak Biswarup
Published: August 2023

Achieving high throughput protein sequencing at single molecule resolution remains a daunting challenge. Herein, relying on a solid‐state 2D phosphorene nanoslit device, an extraordinary biosensor to rapidly identify the key signatures of all twenty amino acids using an interpretable machine learning (ML) model is reported. The XGBoost regression algorithm allows the determination of the transmission function of all twenty amino acids with high accuracy. The resultant ML and DFT studies reveal that it is possible to identify individual amino acids through transmission and current signals readouts with high sensitivity and selectivity. Moreover, we thoroughly compared our results to those from graphene nanoslit and found that the phosphorene nanoslit device can be an ideal candidate for protein sequencing up to a 20‐fold increase in transmission sensitivity. The present study facilitates high throughput screening of all twenty amino acids and can be further extended to other biomolecules for disease diagnosis and therapeutic decision making.
Structural Insight on Supramolecular Polyion Salts: Inositol Hexaphosphate Enclosed in Cationic Macrocyclic Clusters
Authors: Pramanik Subhamay , Steinert Ryan M. , Mitchell‐Koch Katie R. , Bowman‐James Kristin
Published: August 2023

Supramolecular macrocyclic forces have been used to trap phytate, myo‐inositol‐1,2,3,4,5,6‐hexakisphosphate, a key bioanion with multiple roles in metabolic processes. Due to the complex chemistry of six multivalent phosphates surrounding the small, cyclic inositol framework, crystallographic information of simple phytate salts has been elusive. This report represents a combined crystallographic, theoretical, and solution binding investigation of a supramolecular macrocyclic complex of phytate. Together, the results provide significant insight to phytate's intramolecular and intermolecular interactions at the microenvironment level. The macrocycle‐phytate aggregates consist of phytate anionic pairs, each partly sandwiched by two 24‐membered, amide/amine‐based cationic macrocycles. The phytate ion pairs hold the tetrameric macrocyclic array together by six strong intermolecular hydrogen bonds. Both phytates crystallize in 1a5e phosphate conformations (one axial (P2) and five equatorial phosphates). Solution NMR binding studies in 1 : 1 DMSO‐d6 : D2O indicate 2 : 1 macrocycle:phytate associations, suggesting that the sandwich‐like nature of the complex holds together in solution. DFT studies indicate the likely occurrence of dynamic intramolecular interchange of phosphate protons, as well as important roles for the axial (P2) phosphate in both intramolecular and intermolecular hydrogen bonding interactions.
Sensitization patterns to Poaceae pollen indicates a hierarchy in allergens and a lead of tropical grasses
Authors: Rodinkova Victoria , Yuriev Serhii , Mokin Vitalii , Sharikadze Olena , Kryzhanovskyi Yevhenii , Kremenska Lilia , Kaminska Olha , Kurchenko Andrii
Published: August 2023

Background

The allergenicity of pollen of Poaceae family members is a well‐known and confirmed fact. Using the data of component‐resolved molecular diagnostics of allergy, we set a goal to establish the population and individual characteristics of sensitization to grass pollen and assess the patterns of its development.

Methods

Multiplex allergy Alex2 test results of 20,033 patients were used. In addition to descriptive statistics to uncover traits of the sensitized population, statistical inference was utilized to establish the conditional probability of sensitisation, the nature of links between allergens, and the most frequent combinations of allergens in individual patient profiles.

Results

Sensitivity to grass pollen comprised 30.79% of the studied sample. Children accounted for 62.21%, adults—37.79%. Sensitisation to Phl p 1, Lol p 1, and Cyn d 1 was the most frequent in all age groups. Among them, Phl p 1 and Lol p 1 were the major ones. Phl p 2, Phl p 5.0101, and Phl p 6 were also responsible for primary sensitization; Phl p 5.0101 promoted the highest sIgE levels. A combination “Lol p 1—Phl p 1”, where Lol p 1 might play a leading role, was most frequent in individual profiles. Monosensitization to Phl p 2 was the second most frequent and Bayesian Network suggested its independent development. Monosensitization to Cyn d 1, especially among children, may indicate the impact of climate change, promoting the spread of the subtropical grasses to the temperate region.

Conclusions

Descriptive statistics and known clinical data coincide well with statistical inference results and can provide for new clinical insights.
Depression, anxiety, and the risk of cancer: An individual participant data meta‐analysis
Authors: van Tuijl Lonneke A. , Basten Maartje , Pan Kuan‐Yu , Vermeulen Roel , Portengen Lützen , de Graeff Alexander , Dekker Joost , Geerlings Mirjam I. , Hoogendoorn Adriaan , Lamers Femke , Voogd Adri C. , Abell Jessica , Awadalla Philip , Beekman Aartjan T. F. , Bjerkeset Ottar , Boyd Andy , Cui Yunsong , Frank Philipp , Galenkamp Henrike , Garssen Bert , Hellingman Sean , Huisman Martijn , Huss Anke , de Jong Trynke R. , Keats Melanie R. , Kok Almar A. L. , Krokstad Steinar , van Leeuwen Flora E. , Luik Annemarie I. , Noisel Nolwenn , Onland‐Moret N. Charlotte , Payette Yves , Penninx Brenda W. J. H. , Rissanen Ina , Roest Annelieke M. , Ruiter Rikje , Schoevers Robert A. , Soave David , Spaan Mandy , Steptoe Andrew , Stronks Karien , Sund Erik R. , Sweeney Ellen , Twait Emma L. , Teyhan Alison , Verschuren W. M. Monique , van der Willik Kimberly D. , Rosmalen Judith G. M. , Ranchor Adelita V.
Published: August 2023

Background

Depression and anxiety have long been hypothesized to be related to an increased cancer risk. Despite the great amount of research that has been conducted, findings are inconclusive. To provide a stronger basis for addressing the associations between depression, anxiety, and the incidence of various cancer types (overall, breast, lung, prostate, colorectal, alcohol‐related, and smoking‐related cancers), individual participant data (IPD) meta‐analyses were performed within the Psychosocial Factors and Cancer Incidence (PSY‐CA) consortium.

Methods

The PSY‐CA consortium includes data from 18 cohorts with measures of depression or anxiety (up to N = 319,613; cancer incidences, 25,803; person‐years of follow‐up, 3,254,714). Both symptoms and a diagnosis of depression and anxiety were examined as predictors of future cancer risk. Two‐stage IPD meta‐analyses were run, first by using Cox regression models in each cohort (stage 1), and then by aggregating the results in random‐effects meta‐analyses (stage 2).

Results

No associations were found between depression or anxiety and overall, breast, prostate, colorectal, and alcohol‐related cancers. Depression and anxiety (symptoms and diagnoses) were associated with the incidence of lung cancer and smoking‐related cancers (hazard ratios [HRs], 1.06–1.60). However, these associations were substantially attenuated when additionally adjusting for known risk factors including smoking, alcohol use, and body mass index (HRs, 1.04–1.23).

Conclusions

Depression and anxiety are not related to increased risk for most cancer outcomes, except for lung and smoking‐related cancers. This study shows that key covariates are likely to explain the relationship between depression, anxiety, and lung and smoking‐related cancers.

Preregistration number

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=157677.
A retrospective analysis of immune checkpoint inhibitors in patients with preexisting organ dysfunction
Authors: Kesireddy Meghana , Marr Alissa , Schissel Makayla , Ganti Apar K.
Published: August 2023

Background

There are limited to no data regarding the use of immune checkpoint inhibitors (ICIs) in patients who have preexisting organ dysfunction because these patients are frequently excluded from clinical trials. The authors’ objective was to evaluate the effects of ICIs in patients with chronic kidney disease (CKD), cirrhosis, chronic obstructive pulmonary disease (COPD), and congestive heart failure (CHF).

Methods

Data were obtained retrospectively for patients older than 18 years with solid organ malignancies who received at least one dose of an ICI between January 1, 2015, and January 1, 2021, and had either CKD (n = 90), cirrhosis (n = 20), COPD (n = 142), or CHF (n = 82) before ICI initiation at the authors’ institution. Descriptive statistics were used to summarize patient characteristics, treatment characteristics, immune‐related adverse events (IrAEs), and outcomes. An independent samples t‐test or the Wilcoxon rank‐sum test was used to assess differences in continuous variables; the χ2 test or the Fisher exact test was used to assess differences in categorical variables between patients with and without IrAEs. Progression‐free survival (PFS) was assessed using Kaplan–Meier curves, and the log‐rank test was used to assess differences in PFS.

Results

In all four cohorts, there were no statistically significant differences in patient characteristics, treatment characteristics, or outcomes, such as the number of hospitalizations and PFS, among those who experienced IrAEs compared with those who did not. In the CKD cohort, patients with IrAEs were significantly less likely to die than those without IrAEs (52% vs. 81% [p = .009] for all patients; 53% vs. 83% [p = .008] for patients with stage II/III disease who received no definitive local treatment and patients with stage IV disease); this difference was not observed in the cirrhosis, COPD, or CHF cohorts. There was no statistically significant difference in the number of heart failure and COPD exacerbations during the receipt of ICIs in the CHF and COPD cohorts, respectively. The incidence and time to onset of IrAEs in this study appeared to be similar to those reported previously in clinical trials that excluded patients with significant comorbidities.

Conclusions

The current results demonstrate that ICIs are well tolerated by patients who have preexisting organ dysfunction.
Combined Afirma Genomic Sequencing Classifier and TERT promoter mutation detection in molecular assessment of Bethesda III–VI thyroid nodules
Authors: Ladenson Paul W. , Klopper Joshua P. , Hao Yangyang , Kaushik Praveen , Walsh P. Sean , Huang Jing , Kloos Richard T. , Ali Syed Z.
Published: August 2023

Molecular analysis of thyroid nodules can provide diagnostic and prognostic information as well as indicate opportunities for targeted therapy. Whole RNA exome analysis offers information that can be leveraged to predict tumor behavior.
Photoexcited Carrier Transfer in CuInS2 Nanocrystal Assembly by Suppressing Resonant‐Energy Transfer
Authors: Hamanaka Yasushi , Okuyama Satoshi , Yokoi Rin , Kuzuya Toshihiro , Takeda Keiki , Sekine Chihiro
Published: August 2023

High‐density assemblies or superlattice structures composed of colloidal semiconductor nanocrystals have attracted attention as key materials for next‐generation photoelectric conversion devices such as quantum‐dot solar cells. In these nanocrystal solids, unique transport and optical phenomena occur due to quantum coupling of localized energy states, charge‐carrier hopping, and electromagnetic interactions among closely arranged nanocrystals. In particular, the photoexcited carrier dynamics in nanocrystal solids is important because it significantly affects various device parameters. In this study, we report the photoexcited carrier dynamics in a solid film of CuInS2 nanocrystals, which is one of the potential nontoxic substitutes with Cd‐ and Pb‐free compositions. Meanwhile, these subjects have been extensively studied in nanocrystal solids formed by CdSe and PbS systems. A carrier‐hopping mechanism was confirmed using temperature‐dependent photoluminescence spectroscopy, which yielded a typical value of the photoexcited carrier‐transfer rate of (2.2±0.6)×107 s−1 by suppressing the influence of the excitation‐energy transfer.
Use of Real‐World Evidence in Neuroscience‐Related New Drug and Biologics License Applications for Novel Therapeutics
Authors: Bloomfield‐Clagett Bartholt , Rahman Motiur , Smith Kimberly , Concato John
Published: August 2023

The US Food and Drug Administration (FDA) is evaluating the potential use of real‐world evidence (RWE) in regulatory decision making. Some groups have evaluated the use of RWE in regulatory submissions in the United States and abroad, reporting that reliance on RWE to support new product approvals is relatively common. Confusion regarding the use of RWE in drug‐approval decisions may arise, however, based on different application of the terms real‐world data (RWD) and RWE. We evaluated RWE in new drug applications (NDAs) and biologics license applications (BLAs) from January 2019 to June 2021 for novel drugs and biologics approved by the FDA with indications related to psychiatry, neurology, pain, or sedation (here, termed neuroscience‐related). We sought to determine whether the submissions included RWE and to describe the types of data and study designs used. Thirty neuroscience‐related NDAs or BLAs were identified for novel drugs and biologics approved during the time‐period of interest. Among these approvals, three applications (10%) were adjudicated as containing RWE, one of which included RWE as primary evidence of effectiveness. Our findings highlight how different operational definitions of the terms RWD and RWE can result in demonstrably different reporting of the use of RWE in regulatory decision making for neuroscience‐related novel drugs and biologics. A better understanding of this topic, along with awareness of regulatory definitions of RWE, are important factors to promote accurate tracking and reporting of regulatory submissions involving RWE. These factors can also improve awareness among the stakeholder community regarding the role of RWD and RWE in regulatory decision making.
Mapping the Ultrafast Mechanistic Pathways of Co Photocatalysts in Pure Water through Time‐Resolved X‐ray Spectroscopy
Authors: Velasco Lucia , Liu Cunming , Zhang Xiaoyi , Grau Sergi , Gil‐Sepulcre Marcos , Gimbert‐Suriñach Carolina , Picón Antonio , Llobet Antoni , DeBeer Serena , Moonshiram Dooshaye
Published: August 2023

Nanosecond time‐resolved X‐ray (tr‐XAS) and optical transient absorption spectroscopy (OTA) are applied to study 3 multimolecular photocatalytic systems with [Ru(bpy)3]2+photoabsorber, ascorbic acid electron donor and Co catalysts with methylene (1), hydroxomethylene (2) and methyl (3) amine substituents in pure water. OTA and tr‐XAS of 1 and 2 show that the favored catalytic pathway involves reductive quenching of the excited photosensitizer and electron transfer to the catalyst to form a CoII square pyramidal intermediate with a bonded aqua molecule followed by a CoI square planar derivative that decays within ≈8 μs. By contrast, a CoI square pyramidal intermediate with a longer decay lifetime of ≈35 μs is formed from an analogous CoII geometry for 3 in H2O. These results highlight the protonation of CoI to form the elusive hydride species to be the rate limiting step and show that the catalytic rate can be enhanced through hydrogen containing pendant amines that act as H−H bond formation proton relays.
Mechanistic Insights into Formation of Residual Solid in Lignin Depolymerization
Authors: Lv Kaiqi , Chen Zhengjian , Zhang Jiaheng , Liu Yong , Long Jinxing
Published: August 2023

Current techniques of lignin conversion are challenged by the low carbon utilization efficiency resulting from the severe generation of residual solid (char). Therefore, a better understanding of pathway for char formation is significant and highly desired for lignin valorization. In this work, we propose a fundamental mechanistic insight into char formation in lignin depolymerization, using hydrothermal decomposition as model reaction. The results demonstrate that the char featuring a multi‐layer construction of coke and oligomer contains mainly G units, primarily generated from native G‐lignin and demethoxylation of S‐lignin. Instead, H‐lignin contributes to the formation of volatile monophenols. Furthermore, new methylene bridges form between the benzene rings in lignin, which consequently results in the formation of recalcitrant char. Based on these observations, a plausible mechanism for char formation is proposed and verified by the density functional theory calculation.
A new continuous Class‐E mode based on the general theory of high‐efficiency continuous power amplifier
Authors: Wei Xuepeng , Luo Yonglun , Wu Yulan , Yuan Guoqing , Chang Rong , Hong Guoping
Published: August 2023

By multiplying with the continuous factor (CF), the conventional Class‐
, Class‐J power amplifier (PA) can be expanded to their corresponding continuous modes, resulting in a great degree of freedom for broadband design. However, this method can hardly apply to other types of PAs. In view of this problem, the continuous mode is deeply analyzed from the perspective of equation solving for the first time, and a general theory for high‐efficiency broadband continuous PA design is proposed. In this theory, the continuous impedance space does not rely on a mapping relationship achieved by multiplying with the CF, but on a direct solution of the high‐efficiency equations to obtain the broadband design space. This approach is simpler and has the potential to provide greater design space. As a validation, this theory is used for the analysis of Class‐E PAs and a new continuous Class‐E (NC‐E) PA is presented. With knee‐point voltage and finite harmonics taken into account, this type of PA greatly expands the broadband design space of Class‐E PAs and also has the advantage of harmonic matching. The NC‐E PA is designed and manufactured using GaN HEMT CGH40010F, which achieves 40.6–41.6 dBm output power and 66.2%–74.2% drain efficiency (DE) in the frequency band of 2.5–3.8 GHz.
Role of cytoblock on pleural effusion for diagnosis of malignant disease
Authors: Shahini Labinot , Hoxha Musa , Marku Flamur , Morina Besim , Cena Valon , Kabashi Klodete , Mustafa Luan
Published: August 2023

Background

Thoracocentesis of pleural effusion is a simple technique for pleural fluid examination through cytology. In addition to cytological examination to assess the nature of pleural fluid content, we can also perform more detailed examinations through cytoblocks of residual fluid. These paraffin‐embedded cytoblock samples are important because we can perform examinations as in other bioptic samples. In these samples, immunohistochemical and molecular analyses can be performed.

Methods

Two hundred fifty‐five cytological samples from patients with pleural effusion were examined. In cases in which the presence of malignant cells was identified in the cytological examination, as well as cases that were suspicious but not definitive for the presence of a malignant effusion, a cytoblock was prepared. Histological examination and immunohistochemical analysis were performed.

Results

Among 255 cases with pleural effusion, 152 had the presence of malignant cells and 6 cases were suspicious, but uncertain for the presence of malignant cells, while 86 cases had inflammatory pleural effusion or other pathologies but were not malignant. After histological analysis of the cytoblock and immunohistochemical analysis, we identified 82 malignant tumors of the lung, 8 malignant tumors of the gastrointestinal tract, 15 malignant tumors of the breast, and 6 malignant tumors of the female genital tract, as well as 24 tumors of undetermined origin.

Conclusions

Cytoblocks are important for the diagnosis of the primary nature of malignant pleural effusions. The highest importance is primary lung tumors, as well as those tumors in which the primary site of the tumor cannot be determined clinically.
Detection of doping peptides and basic drugs in equine urine using liquid chromatography–mass spectrometry
Authors: Flores Luis , Hargrave Sabine , Clifford Amel , Alarcio Gwendolyne , Moeller Benjamin C.
Published: August 2023

The abuse of prohibited agents including peptides and basic small‐molecule drugs is an area of great concern in horseracing due to their high potential to act as doping agents. These compound classes include agents such as growth hormone‐releasing peptides, peptide analgesics, beta‐2‐adrenergic receptor agonists, and quaternary ammonium drugs that can be challenging to detect and regulate because of their chemical properties and potential rapid elimination following administration. The use of highly sensitive and selective analytical techniques such as liquid chromatography–mass spectrometry (LC–MS) is necessary to provide coverage of these substances and their potential metabolites. This study describes the development and validation of methodology capable of the detection of over 50 different peptide‐based doping agents, related secretagogues, quaternary ammonium drugs, and other challenging small molecules in equine urine following solid‐phase extraction using a mixed mode weak cation exchange sorbent. Following sample extraction, the compounds were analyzed using LC–MS with chromatographic separation via a reverse phase gradient and detection via selective reaction monitoring following introduction to a triple‐stage quadrupole mass spectrometer using positive mode electrospray ionization. Validation parameters including limits of detection and quantitation, accuracy, precision, linear range, recovery, stability, and matrix effects were determined. Briefly, the limits of detection for most compounds were in the sub‐ng/mL ranges with adequate precision and accuracy sufficient for an initial testing procedure. Stability studies indicated that most compounds were sufficiently stable to allow for effective screening using conditions commonly utilized in drug testing laboratories.
Fission–fusion dynamics in the social networks of a North American pitviper
Authors: Tetzlaff Sasha J. , Vizentin‐Bugoni Jeferson , Sperry Jinelle H. , Davis Mark A. , Clark Rulon W. , Repp Roger A. , Schuett Gordon W.
Published: August 2023

Many animal species exist in fission–fusion societies, where the size and composition of conspecific groups change spatially and temporally. To help investigate such phenomena, social network analysis (SNA) has emerged as a powerful conceptual and analytical framework for assessing patterns of interconnectedness and quantifying group‐level interactions. We leveraged behavioral observations via radiotelemetry and genotypic data from a long‐term (>10 years) study on the pitviper Crotalus atrox (western diamondback rattlesnake) and used SNA to quantify the first robust demonstration of social network structures for any free‐living snake. Group‐level interactions among adults in this population resulted in structurally modular networks (i.e., distinct clusters of interacting individuals) for fidelis use of communal winter dens (denning network), mating behaviors (pairing network), and offspring production (parentage network). Although the structure of each network was similar, the size and composition of groups varied among them. Specifically, adults associated with moderately sized social groups at winter dens but often engaged in reproductive behaviors—both at and away from dens—with different and fewer partners. Additionally, modules formed by individuals in the pairing network were frequently different from those in the parentage network, likely due to multiple mating, long‐term sperm storage by females, and resultant multiple paternity. Further evidence for fission–fusion dynamics exhibited by this population—interactions were rare when snakes were dispersing to and traversing their spring–summer home ranges (to which individuals show high fidelity), despite ample opportunities to associate with numerous conspecifics that had highly overlapping ranges. Taken together, we show that long‐term datasets incorporating SNA with spatial and genetic information provide robust and unique insights to understanding the social structure of cryptic taxa that are understudied.
Can Bengal Tiger (Panthera tigris tigris) endure the future climate and land use change scenario in the East Himalayan Region? Perspective from a multiple model framework
Authors: Deka Jyotish Ranjan , Ali Sk. Zeeshan , Ahamad Mujahid , Borah Priyanka , Gopi Govindan Veeraswami , Badola Ruchi , Sharma Rabindra , Hussain Syed Ainul
Published: August 2023

Large mammals are susceptible to land use and climate change, unless they are safeguarded within large, protected areas. It is crucial to comprehend the effects of these changes on mammals to develop a conservation plan. We identified ecological hotspots that can sustain an ecosystem for the endangered Bengal tiger (Panthera tigris tigris), an umbrella species. We developed three distinct ensemble species distribution models (SDMs) for the Bengal tiger in the Indian East Himalayan Region (IEHR). The first model served as the baseline and considered habitat type, climate, land cover, and anthropogenic threats. The second model focused on climate, land use, and anthropogenic threats, the third model focused on climate variables. We projected the second and third models onto two future climate scenarios: RCP 4.5 and RCP 8.5. We evaluated the threats possess to protected areas within eco‐sensitive zone based on the potential tiger habitat. Finally, we compared the potential habitat with the IUCN tiger range. Our study revealed that the Brahmaputra valley will serve as the primary habitat for tigers in the future. However, considering the projected severe climate scenarios, it is anticipated that tigers will undergo a range shift towards the north and east, especially in high‐altitude regions. Very high conservation priority areas, which make up 3.4% of the total area, are predominantly located in the riverine corridor of Assam. High conservation priority areas, which make up 5.5% of total area are located in Assam and Arunachal Pradesh. It is important to note that conservation priority areas outside of protected areas pose a greater threat to tigers. We recommend reassessing the IUCN Red List's assigned range map for tigers in the IEHR, as it is over‐predicted. Our study has led us to conclude both land use and climate change possess threats to the future habitat of tigers. The outcomes of our study will provide crucial information on identifying habitat hotspots and facilitate appropriate conservation planning efforts.
Ecogroups and maternal haplogroups reveal the ancestral origin of native Chinese goat populations based on the variation of mtDNA D‐loop sequences
Authors: Qin Wenjuan , Chen Daosong , Guo Panpan , Hu Lixing , Zheng Xiaodong , Cheng Jin , Chen Hongquan
Published: August 2023

China is rich in goat breeding resources. Officially recognized local goat breeds are mainly distributed in agro‐ecological regions. The population structure and matrilineal origin of native Chinese goats can be used to formulate protection and utilization strategies for these genetic resources. In this study, the genetic structure and maternal origin of native Chinese goats were investigated using mtDNA D‐loop sequences. A total of 329 goat samples from 25 Chinese indigenous goat populations and five introduced goat breeds from abroad were collected; these populations were distributed in four ecogroups designated as Southwest, South‐central, the North China Plain, and Foreign‐ecogroup. A larger average number of nucleotide differences and richer nucleotide diversity were observed in South‐central and Foreign‐ecogroup, whereas these were lower in Southwest. The 216 haplotypes divided into several haplogroups, of which HapA contained 99 haplotypes distributed in Southwest, the North China Plain, and Foreign‐ecogroup with high frequency (0.53–0.77), whereas the frequency of HapA in South‐central was <0.09. HapB was mostly found in South‐central (0.5538) and was distributed to the North China Plain (0.2667), while it was rare in Southwest (<0.08) and Foreign‐ecogroup (<0.07). According to the estimation of kinship and ancestry, HapA had five ancestors (A2, A3, A5, A10, and A12), HapB had a single maternal ancestor (A8), and HapC had two maternal ancestors (A1 and A4). This study showed that native Chinese goat breeds were mainly divided into three haplogroups (HapA, HapB, and HapC) and goat populations have expanded in the ecological regions.