bluuebunny/crossref_metadata_2025 huggingface dataset:
AutoFibroNet: A deep learning and multi‐photon microscopy‐derived automated network for liver fibrosis quantification in MAFLD
Authors: Zhan Huiling , Chen Siyu , Gao Feng , Wang Guangxing , Chen Sui‐Dan , Xi Gangqin , Yuan Hai‐Yang , Li Xiaolu , Liu Wen‐Yue , Byrne Christopher D. , Targher Giovanni , Chen Miao‐Yang , Yang Yong‐Feng , Chen Jun , Fan Zhiwen , Sun Xitai , Cai Guorong , Zheng Ming‐Hua , Zhuo Shuangmu ,   CHESS‐MAFLD consortium
Published: July 2023

Background

Liver fibrosis is the strongest histological risk factor for liver‐related complications and mortality in metabolic dysfunction‐associated fatty liver disease (MAFLD). Second harmonic generation/two‐photon excitation fluorescence (SHG/TPEF) is a powerful tool for label‐free two‐dimensional and three‐dimensional tissue visualisation that shows promise in liver fibrosis assessment.

Aim

To investigate combining multi‐photon microscopy (MPM) and deep learning techniques to develop and validate a new automated quantitative histological classification tool, named AutoFibroNet (Automated Liver Fibrosis Grading Network), for accurately staging liver fibrosis in MAFLD.

Methods

AutoFibroNet was developed in a training cohort that consisted of 203 Chinese adults with biopsy‐confirmed MAFLD. Three deep learning models (VGG16, ResNet34, and MobileNet V3) were used to train pre‐processed images and test data sets. Multi‐layer perceptrons were used to fuse data (deep learning features, clinical features, and manual features) to build a joint model. This model was then validated in two further independent cohorts.

Results

AutoFibroNet showed good discrimination in the training set. For F0, F1, F2 and F3‐4 fibrosis stages, the area under the receiver operating characteristic curves (AUROC) of AutoFibroNet were 1.00, 0.99, 0.98 and 0.98. The AUROCs of F0, F1, F2 and F3‐4 fibrosis stages for AutoFibroNet in the two validation cohorts were 0.99, 0.83, 0.80 and 0.90 and 1.00, 0.83, 0.80 and 0.94, respectively, showing a good discriminatory ability in different cohorts.

Conclusion

AutoFibroNet is an automated quantitative tool that accurately identifies histological stages of liver fibrosis in Chinese individuals with MAFLD.
Word embeddings reveal growing moral concern for people, animals and the environment
Authors: Leach Stefan , Kitchin Andrew P. , Sutton Robbie M.
Published: July 2023

The Enlightenment idea of historical moral progress asserts that civil societies become more moral over time. This is often understood as an expanding moral circle and is argued to be tightly linked with language use, with some suggesting that shifts in how we express concern for others can be considered an important indicator of moral progress. Our research explores these notions by examining historical trends in natural language use during the 19th and 20th centuries. We found that the associations between words denoting moral concern and words referring to people, animals, and the environment grew stronger over time. The findings support widely‐held views about the nature of moral progress by showing that language has changed in a way that reflects greater concern for others.
Cathepsins and SARS‐CoV‐2 infection: From pathogenic factors to potential therapeutic targets
Authors: Zhao Shuxuan , Jiang Muzhou , Qing Hong , Ni Junjun
Published: July 2023

Coronavirus disease‐19 (COVID‐19) is caused by severe acute respiratory syndrome‐coronavirus‐2 (SARS‐CoV‐2) infection. The COVID‐19 pandemic began in March 2020 and has wrought havoc on health and economic systems worldwide. Efficacious treatment for COVID‐19 is lacking: Only preventive measures as well as symptomatic and supportive care are available. Preclinical and clinical studies have indicated that lysosomal cathepsins might contribute to the pathogenesis and disease outcome of COVID‐19. Here, we discuss cutting‐edge evidence on the pathological roles of cathepsins in SARS‐CoV‐2 infection, host immune dysregulations, and the possible underlying mechanisms. Cathepsins are attractive drug targets because of their defined substrate‐binding pockets, which can be exploited as binding sites for pharmaceutical enzyme inhibitors. Accordingly, the potential modulatory strategies of cathepsin activity are discussed. These insights could shed light on the development of cathepsin‐based interventions for COVID‐19.
Acacetin restrains the malignancy of esophageal squamous carcinoma cells via regulating JAK2/STAT3 pathway
Authors: Wang Wei , Renquan Zhang
Published: July 2023

Acacetin is a natural flavonoid compound found in diverse plants, which has strong anti‐inflammatory and anti‐cancer activities. This work aimed at investigating how acacetin functions on esophageal squamous carcinoma cells. In this work, esophageal squamous carcinoma cell lines were subjected to increasing doses of acacetin, and the proliferative, migrative, invasive and apoptotic phenotypes were evaluated by a series of in vitro experiments. Genes related to acacetin and esophageal cancer were predicted by bioinformatics analysis. The levels of apoptosis‐relevant proteins and JAK2/STAT3 pathway‐relevant proteins in esophageal squamous carcinoma cells were probed by Western blot. It was revealed that acacetin could block the growth and aggressiveness of TE‐1 and TE‐10 cells and promote the apoptosis. Acacetin treatment induced bax's expression and repressed bcl‐2's expression. Notably, acacetin inhibits JAK2/STAT3 pathway in esophageal squamous carcinoma cells. In summary, acacetin inhibits the malignant progression of esophageal squamous carcinoma via restraining JAK2/STAT3 signaling.
Mucosal adhesion phenomenon after maxillary sinus floor elevation: A preclinical study
Authors: Nakajima Yasushi , Apaza Alccayhuaman Karol Alí , Botticelli Daniele , Lang Niklaus Peter , De Rossi Ermenegildo Federico , Xavier Samuel Porfirio
Published: July 2023

Aim

To describe the histological events that occur after maxillary sinus floor elevation when the elevated and undetached sinus mucosa are in close proximity or in contact with each other.

Materials and methods

From 76 rabbits, 152 elevated maxillary sinuses were analyzed histologically. Sites without adhesions were classified as “No proximity,” whereas the adhesion stages were divided into “Proximity,” “Fusion,” and “Synechia stages.” The width of the pseudostratified columnar epithelium and the distance between the two layers of the elevated and undetached sinus mucosae were measured at various standardized positions.

Results

Thirty‐one sites presenting with adhesions were found. Twelve sites were in the proximity stage,” presenting cilia of the two epithelial layers that were shortened and interlinked within the mucous context. Hyperactivity of the goblet cells was also observed. In the other cases, the hyperplastic epithelium showed attempts to reach the contralateral mucosa. The 15 “fusion stage” sites presented regions with epithelial cells of the two mucosal layers that penetrated each other. Four sites presented “synechiae stages,” represented by bridges of connective tissue connecting the two lamina propria.

Conclusions

Close proximity or tight contact between the elevated and undetached mucosa adhering to the bone walls might occur after maxillary sinus floor elevation. This induced hyperplasia of the epithelial cells and adhesion of the two layers until synechiae formation.
Policy generation network for zero‐shot policy learning
Authors: Qian Yiming , Zhang Fengyi , Liu Zhiyong
Published: July 2023

Lifelong reinforcement learning is able to continually accumulate shared knowledge by estimating the inter‐task relationships based on training data for the learned tasks in order to accelerate learning for new tasks by knowledge reuse. The existing methods employ a linear model to represent the inter‐task relationships by incorporating task features in order to accomplish a new task without any learning. But these methods may be ineffective for general scenarios, where linear models build inter‐task relationships from low‐dimensional task features to high‐dimensional policy parameters space. Also, the deficiency of calculating errors from objective function may arise in the lifelong reinforcement learning process when some errors of policy parameters restrain others due to inter‐parameter correlation. In this paper, we develop a policy generation network that nonlinearly models the inter‐task relationships by mapping low‐dimensional task features to the high‐dimensional policy parameters, in order to represent the shared knowledge more effectively. At the same time, we propose a novel objective function of lifelong reinforcement learning to relieve the deficiency of calculating errors by adding weight constraints for errors. We empirically demonstrate that our method improves the zero‐shot policy performance across a variety of dynamical systems.
Neutrophilic fixed drug eruption, a histopathologic variant or an expected finding?—A report of two cases and review of the literature
Authors: Theroux Zachary , Gardner Jerad , Ortiz Eduardo , Kosik Grace , Junkins‐Hopkins Jacqueline
Published: July 2023

Fixed drug eruption (FDE) is an adverse drug reaction characterized by recurrent circumscribed lesions at the same location upon re‐exposure to the culprit medication, resulting in distinct postinflammatory hyperpigmentation. Histopathologically, FDE demonstrates a predominantly lymphocytic interface or lichenoid infiltrate with basal cell vacuolar changes and keratinocyte dyskeratosis/apoptosis. The term “neutrophilic fixed drug eruption” has been used to describe cases in which the inflammatory infiltrate is predominantly neutrophilic. The infiltrate can extend deeper in the dermis, potentially mimicking a neutrophilic dermatosis such as Sweet syndrome. We present two cases and review the literature to discuss the possibility that a neutrophilic inflammatory infiltrate may be an expected finding in FDE, rather than a histopathologic variant.
Effects of the COVID‐19 pandemic on inpatient skin surgery in Germany: results of the DESSI‐survey
Authors: Balakirski Galina , Hofmann Silke C. , Isselmann Nataliia , Giordano Anna , Dippel Edgar , Löser Christoph R.
Published: July 2023

Background

The aim of the survey was to investigate a possible impairment of inpatient dermatological and dermatosurgical care in Germany due to the COVID‐19 pandemic.

Methods

An online survey on the impact of pandemic‐related measures on inpatient care was sent to all German dermatology clinics. Only one person per clinic was asked to participate. Data analysis was mainly descriptive. Differences between university hospitals and non‐university hospitals were calculated using the Chi‐square test.

Results

From the 113 dermatological clinics with inpatient care, we received 45 (39.8%) at least partially completed questionnaires. Of these, 25 (55.6%) came from university hospitals, 18 (40.0%) from teaching hospitals of a university, 1 (2.2%) from a non‐teaching hospital, and 1 (2.2%) from a participant who did not provide any information on his facility. More than half of survey participants (57.8%) reported that many elective skin surgeries had to be canceled at their clinics at the beginning of the COVID‐19 pandemic. However, most of the clinics (75.6%) were able to perform medically necessary surgeries (such as for malignant melanoma). Only 28.9% (13/45) of participants reported that skin surgery in their clinics returned to full strength after the COVID‐19 pandemic. There was no statistically significant difference between university hospitals and non‐university hospitals regarding the influence of COVID‐19‐related restrictions.

Conclusions

Despite their heterogeneity, the results of the survey show an overall clear and long‐term pandemic‐related impairment of inpatient dermatology and skin surgery in Germany.
Designing supply chain strategies against epidemic outbreaks such as COVID‐19: Review and future research directions
Authors: Govindan Kannan , Sethi Suresh P. , Cheng T. C. E. , Lu Susan Feng
Published: July 2023

The supply chain is vulnerable to disruptions, which can lead to operational failure. Therefore, it is crucial to investigate and monitor the risks associated with such disruptions. Epidemics, including the profound impact of COVID‐19, exemplify disruptive risks that engender complexities throughout the value chain. COVID‐19 has caused significant disruptions to the global supply chain due to the preexisting fragile supply chains, resulting in the unavailability of essential raw materials, halts in production, and imbalances between supply and demand. It has forced the supply chain community to rethink their risk mitigation strategies. Despite its significance, there are a few studies on the existing options and strategies to mitigate the risks associated with epidemics such as COVID‐19. This special issue explores state‐of‐the‐art knowledge of various risks and their mitigation strategies, presenting optimized models and solutions. This editorial seeks to introduce valuable insights and illuminate promising avenues for future research by reviewing existing studies. The comprehensive understanding derived from this editorial and the accompanying articles of this special issue will benefit both researchers and practitioners, enabling them to navigate the multifaceted landscape of epidemic‐induced disruptive risks in the supply chain and adopt suitable mitigation strategies. Furthermore, this special issue lays a solid foundation for implementing advanced methods for managing and mitigating the disruptive risks that epidemics pose to the supply chain.
Children with developmental dyslexia have equivalent audiovisual speech perception performance but their perceptual weights differ
Authors: Gijbels Liesbeth , Lee Adrian K. C. , Yeatman Jason D.
Published: July 2023

As reading is inherently a multisensory, audiovisual (AV) process where visual symbols (i.e., letters) are connected to speech sounds, the question has been raised whether individuals with reading difficulties, like children with developmental dyslexia (DD), have broader impairments in multisensory processing. This question has been posed before, yet it remains unanswered due to (a) the complexity and contentious etiology of DD along with (b) lack of consensus on developmentally appropriate AV processing tasks. We created an ecologically valid task for measuring multisensory AV processing by leveraging the natural phenomenon that speech perception improves when listeners are provided visual information from mouth movements (particularly when the auditory signal is degraded). We designed this AV processing task with low cognitive and linguistic demands such that children with and without DD would have equal unimodal (auditory and visual) performance. We then collected data in a group of 135 children (age 6.5–15) with an AV speech perception task to answer the following questions: (1) How do AV speech perception benefits manifest in children, with and without DD? (2) Do children all use the same perceptual weights to create AV speech perception benefits, and (3) what is the role of phonological processing in AV speech perception? We show that children with and without DD have equal AV speech perception benefits on this task, but that children with DD rely less on auditory processing in more difficult listening situations to create these benefits and weigh both incoming information streams differently. Lastly, any reported differences in speech perception in children with DD might be better explained by differences in phonological processing than differences in reading skills.

Research Highlights

Children with versus without developmental dyslexia have equal audiovisual speech perception benefits, regardless of their phonological awareness or reading skills.

Children with developmental dyslexia rely less on auditory performance to create audiovisual speech perception benefits.

Individual differences in speech perception in children might be better explained by differences in phonological processing than differences in reading skills.
Heart failure in patients is associated with downregulation of mitochondrial quality control genes
Authors: Svagusa T. , Sikiric S. , Milavic M. , Sepac A. , Seiwerth S. , Milicic D. , Gasparovic H. , Biocina B. , Rudez I. , Sutlic Z. , Manola S. , Varvodic J. , Udovicic M. , Urlic M. , Ivankovic S. , Plestina S. , Paic F. , Kulic A. , Bakovic P. , Sedlic F.
Published: July 2023

Background

Mitochondrial dysfunction is one of key factors causing heart failure. We performed a comprehensive analysis of expression of mitochondrial quality control (MQC) genes in heart failure.

Methods

Myocardial samples were obtained from patients with ischemic and dilated cardiomyopathy in a terminal stage of heart failure and donors without heart disease. Using quantitative real‐time PCR, we analysed a total of 45 MQC genes belonging to mitochondrial biogenesis, fusion‐fission balance, mitochondrial unfolded protein response (UPRmt), translocase of the inner membrane (TIM) and mitophagy. Protein expression was analysed by ELISA and immunohistochemistry.

Results

The following genes were downregulated in ischemic and dilated cardiomyopathy: COX1, NRF1, TFAM, SIRT1, MTOR, MFF, DNM1L, DDIT3, UBL5, HSPA9, HSPE1, YME1L, LONP1, SPG7, HTRA2, OMA1, TIMM23, TIMM17A, TIMM17B, TIMM44, PAM16, TIMM22, TIMM9, TIMM10, PINK1, PARK2, ROTH1, PARL, FUNDC1, BNIP3, BNIP3L, TPCN2, LAMP2, MAP1LC3A and BECN1. Moreover, MT‐ATP8, MFN2, EIF2AK4 and ULK1 were downregulated in heart failure from dilated, but not ischemic cardiomyopathy. VDAC1 and JUN were only genes that exhibited significantly different expression between ischemic and dilated cardiomyopathy. Expression of PPARGC1, OPA1, JUN, CEBPB, EIF2A, HSPD1, TIMM50 and TPCN1 was not significantly different between control and any form of heart failure. TOMM20 and COX proteins were downregulated in ICM and DCM.

Conclusions

Heart failure in patients with ischemic and dilated cardiomyopathy is associated with downregulation of large number of UPRmt, mitophagy, TIM and fusion‐fission balance genes. This indicates multiple defects in MQC and represents one of potential mechanisms underlying mitochondrial dysfunction in patients with heart failure.
Context‐dependent expression of variation in defensive behaviour in the lower termite Zootermopsis nevadensis
Authors: Koyama Yutaro , Yaguchi Hajime , Maekawa Kiyoto , Hojo Masaru K.
Published: July 2023

Eusocial animals exhibit a sophisticated division of labour. The self‐organized colony requires coordination of local interactions at the individual level. Termites are a well‐known group exhibiting social organization among castes within a colony, and helper castes have facilitated their ecological and evolutionary success. Termites have soldier castes specialized in defence, but other castes are also known to exhibit defensive behaviour depending on the context. However, it is unclear how variation in the frequencies of defensive behaviour is emerged. Here, we investigate the effects of the presence of nestmates on individual defensive behaviour in the dampwood termite Zootermopsis nevadensis. We experimentally prepared three conditions and observed biting behaviour against the ant Camponotus obscuripes. First, the frequency of biting was significantly higher in soldiers than that in pseudergates (i.e. workers) under isolated conditions. Second, the results showed that the frequencies of biting exhibited by soldiers were much higher than those of pseudergates in the pseudergate–soldier pairs. Finally, we investigated the social conditions in the presence of the same castes, that is, pseudergate–pseudergate and soldier–soldier pairs. The frequencies of biting exhibited by first‐biting individuals were significantly higher than those exhibited by second‐biting individuals in both paired conditions. Our findings demonstrate that defensive behaviour can be frequently observed in first‐biting individuals despite the presence of two individuals of the same caste, suggesting that the variation of defensive behaviour may be increased in the presence of nestmates.
Identification and characterization of archaeal and bacterial F420‐dependent thioredoxin reductases
Authors: Yang Guang , Wijma Hein J. , Rozeboom Henriëtte J. , Mascotti Maria Laura , Fraaije Marco W.
Published: July 2023

The thioredoxin pathway is an antioxidant system present in most organisms. Electrons flow from a thioredoxin reductase to thioredoxin at the expense of a specific electron donor. Most known thioredoxin reductases rely on NADPH as a reducing cofactor. Yet, in 2016, a new type of thioredoxin reductase was discovered in Archaea which utilize instead a reduced deazaflavin cofactor (F420H2). For this reason, the respective enzyme was named deazaflavin‐dependent flavin‐containing thioredoxin reductase (DFTR). To have a broader understanding of the biochemistry of DFTRs, we identified and characterized two other archaeal representatives. A detailed kinetic study, which included pre‐steady state kinetic analyses, revealed that these two DFTRs are highly specific for F420H2 while displaying marginal activity with NADPH. Nevertheless, they share mechanistic features with the canonical thioredoxin reductases that are dependent on NADPH (NTRs). A detailed structural analysis led to the identification of two key residues that tune cofactor specificity of DFTRs. This allowed us to propose a DFTR‐specific sequence motif that enabled for the first time the identification and experimental characterization of a bacterial DFTR.
Determination of energy dissipation during cyclic loading and its use to predict fatigue life of metal alloys
Authors: Kassapoglou Christos
Published: July 2023

An approach to determine the specific energy dissipated during cyclic loading of metal alloys with load ratios between 0 and 1 is developed. The dissipated energy per cycle is determined by using a limiting procedure to obtain the area enclosed between successive loading and unloading curves and can be used for low‐, medium‐, and high‐cycle fatigue. Comparisons with published data from two aluminum, one titanium, and one steel alloy show that the predictions capture the test results very well. A universal curve relating cycles to failure to two nondimensional parameters is derived. It is shown, in some limiting cases, that the method leads to power law equations with the parameters in these equations determined directly from the complete stress–strain curve of the material with no need to fit experimental data. Furthermore, if certain conditions are satisfied, the method is consistent with the existence of an endurance limit and Miner's rule.
The price impact of analyst revisions and the state of the economy: Evidence around the world
Authors: Su Chen
Published: July 2023

This paper examines the price impact of analyst revisions in distinct economic states around the world. We find stronger average 2‐day cumulative abnormal returns in bad times, though this pattern is mainly observed in developed countries. In addition, trading strategies following analyst revisions, with holding periods from 1 to 6 months, are generally more profitable in good times with lower macroeconomic uncertainty, after controlling for market and common risk factors. The profitability, however, disappears or declines substantially after accounting for time‐varying risk premia conditioned on lagged macroeconomic information, indicating a reduced information production role played by analysts in recent decades.
The papers I can't write
Authors: Schultz Paul
Published: July 2023

In this future directions in finance article, I discuss several topics that I believe are promising areas for research. The topics fall into three areas: the microstructure of fixed income markets, equity market microstructure, and short selling. Both theoretical and empirical work is needed in these areas.
Stimuli‐responsive nanodelivery systems for amplifying immunogenic cell death in cancer immunotherapy
Authors: Xu Wenhao , Liu Wangrui , Yang Jianfeng , Lu Jiahe , Zhang Hailiang , Ye Dingwei
Published: July 2023

Immunogenic cell death (ICD) is a special pattern of tumor cell death, enabling to elicit tumor‐specific immune response via the release of damage‐associated molecular patterns and tumor‐associated antigens in the tumor microenvironment. ICD‐induced immunotherapy holds the promise for completely eliminating tumors and long‐term protective antitumor immune response. Increasing ICD inducers have been discovered for boosting antitumor immunity via evoking ICD. Nonetheless, the utilization of ICD inducers remains insufficient owing to serious toxic reactions, low localization efficiency within the tumor microenvironmental niche, etc. For overcoming such limitations, stimuli‐responsive multifunctional nanoparticles or nanocomposites with ICD inducers have been developed for improving immunotherapeutic efficiency via lowering toxicity, which represent a prospective scheme for fostering the utilization of ICD inducers in immunotherapy. This review outlines the advances in near‐infrared (NIR)‐, pH‐, redox‐, pH‐ and redox‐, or NIR‐ and tumor microenvironment‐responsive nanodelivery systems for ICD induction. Furthermore, we discuss their clinical translational potential. The progress of stimuli‐responsive nanoparticles in clinical settings depends upon the development of biologically safer drugs tailored to patient needs. Moreover, an in‐depth comprehending of ICD biomarkers, immunosuppressive microenvironment, and ICD inducers may accelerate the advance in smarter multifunctional nanodelivery systems to further amplify ICD.
Impact of multi‐output and stacking methods on feed efficiency prediction from genotype using machine learning algorithms
Authors: Mora Mónica , González Pablo , Quevedo José Ramón , Montañés Elena , Tusell Llibertat , Bergsma Rob , Piles Miriam
Published: July 2023

Feeding represents the largest economic cost in meat production; therefore, selection to improve traits related to feed efficiency is a goal in most livestock breeding programs. Residual feed intake (RFI), that is, the difference between the actual and the expected feed intake based on animal's requirements, has been used as the selection criteria to improve feed efficiency since it was proposed by Kotch in 1963. In growing pigs, it is computed as the residual of the multiple regression model of daily feed intake (DFI), on average daily gain (ADG), backfat thickness (BFT), and metabolic body weight (MW). Recently, prediction using single‐output machine learning algorithms and information from SNPs as predictor variables have been proposed for genomic selection in growing pigs, but like in other species, the prediction quality achieved for RFI has been generally poor. However, it has been suggested that it could be improved through multi‐output or stacking methods. For this purpose, four strategies were implemented to predict RFI. Two of them correspond to the computation of RFI in an indirect way using the predicted values of its components obtained from (i) individual (multiple single‐output strategy) or (ii) simultaneous predictions (multi‐output strategy). The other two correspond to the direct prediction of RFI using (iii) the individual predictions of its components as predictor variables jointly with the genotype (stacking strategy), or (iv) using only the genotypes as predictors of RFI (single‐output strategy). The single‐output strategy was considered the benchmark. This research aimed to test the former three hypotheses using data recorded from 5828 growing pigs and 45,610 SNPs. For all the strategies two different learning methods were fitted: random forest (RF) and support vector regression (SVR). A nested cross‐validation (CV) with an outer 10‐folds CV and an inner threefold CV for hyperparameter tuning was implemented to test all strategies. This scheme was repeated using as predictor variables different subsets with an increasing number (from 200 to 3000) of the most informative SNPs identified with RF. Results showed that the highest prediction performance was achieved with 1000 SNPs, although the stability of feature selection was poor (0.13 points out of 1). For all SNP subsets, the benchmark showed the best prediction performance. Using the RF as a learner and the 1000 most informative SNPs as predictors, the mean (SD) of the 10 values obtained in the test sets were: 0.23 (0.04) for the Spearman correlation, 0.83 (0.04) for the zero–one loss, and 0.33 (0.03) for the rank distance loss. We conclude that the information on predicted components of RFI (DFI, ADG, MW, and BFT) does not contribute to improve the quality of the prediction of this trait in relation to the one obtained with the single‐output strategy.
Drug screening of α‐amylase inhibitors as candidates for treating diabetes
Authors: Alp Meryem , Misturini Alechania , Sastre German , Gálvez‐Llompart Maria
Published: July 2023

In the present study, the identification of potential α‐amylase inhibitors is explored as a potential strategy for treating type‐2 diabetes mellitus. A computationally driven approach using molecular docking was employed to search for new α‐amylase inhibitors. The interactions of potential drugs with the enzyme's active site were investigated and compared with the contacts established by acarbose (a reference drug for α‐amylase inhibition) in the crystallographic structure 1B2Y. For this active site characterization, both molecular docking and molecular dynamics simulations were performed, and the residues involved in the α‐amylase–acarbose complex were considered to analyse the potential drug's interaction with the enzyme. Two potential α‐amylase inhibitors (AN‐153I105594 and AN‐153I104845) have been selected following this computational strategy. Both compounds established a large number of interactions with key binding site α‐amylase amino acids and obtained a comparable docking score concerning the reference drug (acarbose). Aiming to further analyse candidates' properties, their ADME (absorption, distribution, metabolism, excretion) parameters, druglikeness, organ toxicity, toxicological endpoints and median lethal dose (LD50) were estimated. Overall estimations are promising for both candidates, and in silico toxicity predictions suggest that a low toxicity should be expected.
Prediction of advanced colorectal neoplasia based on metabolic parameters among symptomatic patients
Authors: Wong Martin C. S. , Leung Eman Yee‐man , Chun Sam C. C. , Wang Harry Hao‐xiang , Huang Junjie
Published: July 2023

Background and Aim

Worldwide, colorectal cancer (CRC) is the third most common cancer and ranks second among the leading causes of cancer death. This study aims to devise and validate a scoring system based on metabolic parameters to predict the risk of advanced colorectal neoplasia (ACN) in a large Chinese population.

Methods

This was a cohort study of 495 584 symptomatic subjects aged 40 years or older who have received colonoscopy in Hong Kong from 1997 to 2017. The algorithm's discriminatory ability was evaluated as the area under the curve (AUC) of the mathematically constructed receiver operating characteristic curve.

Results

Age, male gender, inpatient setting, abnormal aspartate transaminase/alanine transaminase, white blood cell, plasma gamma‐glutamyl transferase, high‐density lipoprotein cholesterol, triglycerides, and hemoglobin A1c were significantly associated with ACN. A scoring of < 2.65 was designated as “low risk (LR).” Scores at 2.65 or above had prevalence higher than the overall prevalence and hence were assigned as “high risk (HR).” The prevalence of ACN was 32% and 11%, respectively, for HR and LR groups. The AUC for the risk score in the derivation and validation cohort was 70.12%.

Conclusions

This study has validated a simple, accurate, and easy‐to‐use scoring algorithm, which has a high discriminatory capability to predict ACN in symptomatic patients. Future studies should examine its predictive performance in other population groups.
Hazardous drinking by older adults with chronic conditions during the COVID‐19 pandemic: Evidence from a Chicago‐based cohort
Authors: Phillips Aryn Z. , Carnethon Mercedes R. , Bonham Morgan , Lovett Rebecca M. , Wolf Michael S.
Published: July 2023

Background

It is unclear how older adults with chronic conditions, who have greater risk of alcohol‐related adverse outcomes, used alcohol throughout the COVID‐19 pandemic. We assess changes in hazardous drinking prevalence May 2020–December 2021 and factors associated with hazardous drinking.

Methods

Data are from structured phone interviews of older adults (age 60+) with chronic conditions (e.g., hypertension, diabetes, pulmonary disease, heart disease) in a Chicago‐based longitudinal cohort (Chicago COVID‐19 Comorbidities survey, Waves 3–7, n = 247). We tested differences in the prevalence of hazardous drinking (defined as AUDIT‐C score of 3+ for women and 4+ for men) across waves for the full sample, by demographic group (sex, race, and ethnicity), and by chronic condition burden (<3 conditions, 3+ conditions). Generalized estimating equations investigated associations of hazardous drinking with sociodemographic and pandemic coping‐related factors (stress, loneliness, outside contacts, depression, anxiety).

Results

Participants were 66.8% female; 27.9% non‐Hispanic Black, 14.2% Hispanic, 4.9% other race. Hazardous drinking was reported by 44.9% of participants in May 2020, but declined to 23.1% by July–August 2020 and continued to slowly decline to 19.4% by September–December 2021. Differences from May 2020 were significant at the 0.05 level. Subgroups followed similar trajectories. Hazardous drinking prevalence was initially higher but declined more among men than women, consistently higher among non‐Hispanic White respondents than among Hispanic and non‐Hispanic Black respondents, and declined more rapidly among adults with 3+ chronic conditions. In adjusted models, race and ethnicity were associated with lower prevalence of hazardous drinking (non‐Hispanic Black: adjusted prevalence ratio [aPR] = 0.50, 95% confidence interval [CI] = 0.33, 0.74; other race: aPR = 0.26, 95% CI = 0.09, 0.81, compared with non‐Hispanic White). No coping‐related factors were significantly associated with hazardous drinking.

Conclusion

Among a cohort of older adults with chronic conditions, almost half engaged in hazardous drinking in early summer of the COVID‐19 pandemic. While prevalence fell, these rates reinforce the need for alcohol screening and intervention in clinical settings among this population.
Correlates of delirium care competency among shift leader nurses in acute medical wards in Japan: A cross‐sectional study
Authors: Matsuda Ken‐ichi , Watanuki Shigeaki
Published: July 2023

Aim

This study identified the correlates of delirium care competency among shift leader nurses in acute medical wards in Japan.

Methods

A cross‐sectional study was conducted from November 2019 to February 2020. We sent request letters to a random sample of 381 general acute care hospitals in Japan. Of these, 68 agreed to participate and distributed 735 self‐administered questionnaires to shift leader nurses working in their acute medical wards. The questionnaire included the Self‐rated Delirium Care Competency Scale for Shift Leader Nurses in Acute Medical Wards (DCSL‐M), developed by the authors. It gathered data on the respondents' demographics and delirium care competency, and investigated a total of 25 variables. We calculated descriptive statistics and examined associations between delirium care competency and the demographics using multiple logistic regression analysis.

Results

Of the total, 301 (40.9%) questionnaires were returned. Delirium care competency was high among shift leader nurses who: (1) had experience as a clinical practice preceptor for nursing students; (2) had experience attending training related to dementia or delirium care; (3) worked at a hospital/ward that charged additional medical fees for dementia care; and (4) had access to consulting psychiatrists to refer patients with delirium.

Conclusions

The results suggest the need for efforts to improve delirium care competency among shift leader nurses who work in hospitals that do not charge additional medical fees for dementia care or that do not have consulting psychiatrists to refer patients with delirium.
Evidence of extraganglionic vagal mechanoreceptors in the mouse vagus nerve
Authors: Leon‐Mercado Luis , Tinajero Arely , Gautron Laurent
Published: July 2023

Vagal afferent neuronal somas are in the nodose and jugular ganglia. In this study, we identified extraganglionic neurons in whole‐mount preparations of the vagus nerves from Phox2b‐Cre‐ZsGreen transgenic mice. These neurons are typically arranged in small clusters and monolayers along the cervical vagus nerve. Although infrequent, these neurons were sometimes observed along the thoracic and esophageal vagus. We performed RNAscope in situ hybridization and confirmed that the extraganglionic neurons detected in this transgenic mouse strain expressed vagal afferent markers (i.e., Phox2b and Slc17a6) as well as markers that identify them as potential gastrointestinal mechanoreceptors (i.e., Tmc3 and Glp1r). We also identified extraganglionic neurons in the vagus nerves of wild‐type mice that were injected intraperitoneally with Fluoro‐Gold, thereby ruling out possible anatomical discrepancies specific for transgenic mice. In wild‐type mice, extraganglionic cells were positive for peripherin, confirming their neuronal nature. Taken together, our findings revealed a previously undiscovered population of extraganglionic neurons associated with the vagus nerve. Going forward, it is important to consider the possible existence of extraganglionic mechanoreceptors that transmit signals from the abdominal viscera in future studies related to vagal structure and function.
Third‐Degree Price Discrimination in Oligopoly when Markets are Covered*
Authors: Dertwinkel‐Kalt Markus , Wey Christian
Published: July 2023

We analyze oligopolistic third‐degree price discrimination relative to uniform pricing when markets are covered. Pricing equilibria are critically determined by supply‐side features such as the number of firms and their marginal cost differences. It follows that each firm's Lerner index under uniform pricing is equal to the weighted harmonic mean of the firm's relative margins under discriminatory pricing. Uniform pricing then lowers average prices and raises consumer surplus. We can calculate the gain in consumer surplus and loss in firms' profits from uniform pricing based only on the market data of the discriminatory equilibrium (i.e., prices and quantities).
Adherence to sleep restriction therapy – An evaluation of existing measures
Authors: Steinmetz Lisa , Simon Laura , Feige Bernd , Riemann Dieter , Akram Umair , Crawford Megan R. , Johann Anna F. , Spiegelhalder Kai
Published: July 2023

Sleep restriction, a key element of cognitive behavioural therapy for insomnia, involves considerable behavioural changes in patients' lives, leading to side‐effects like increased daytime sleepiness. Studies on sleep restriction rarely report adherence, and when assessed it is often limited to the average number of therapy sessions attended. This study aims to systematically evaluate different measures of adherence to cognitive behavioural therapy for insomnia and their relationship with treatment outcome. This is a secondary analysis of data from a randomized controlled trial investigating cognitive behavioural therapy for insomnia (Johann et al. (2020) Journal of Sleep Research, 29, e13102). The sample included 23 patients diagnosed with insomnia according to DSM‐5 criteria who underwent 8 weeks of cognitive behavioural therapy for insomnia. The following adherence measures based on sleep diary data were used: number of sessions completed; deviations from agreed time in bed; average percentage of patients deviating from bedtime by 15, 30 or 60 min; variability of bedtime and wake‐up time; change in time in bed from pre‐ to post‐assessment. Treatment outcome was assessed using the Insomnia Severity Index. Multiple regression models were employed, and insomnia severity was controlled for. Results showed that none of the adherence measures predict insomnia severity. Baseline insomnia severity, dysfunctional thoughts and attitudes about sleep, depression or perfectionism did not predict adherence. The limited variance in the outcome parameter due to most patients benefiting from treatment and the small sample size may explain these findings. Additionally, using objective measures like actigraphy could provide a better understanding of adherence behaviour. Lastly, the presence of perfectionism in patients with insomnia may have mitigated adherence problems in this study.
Alternative splicing of TaHSFA6e modulates heat shock protein–mediated translational regulation in response to heat stress in wheat
Authors: Wen Jingjing , Qin Zhen , Sun Lv , Zhang Yumei , Wang Dongli , Peng Huiru , Yao Yingyin , Hu Zhaorong , Ni Zhongfu , Sun Qixin , Xin Mingming
Published: July 2023

Heat stress greatly threatens crop production. Plants have evolved multiple adaptive mechanisms, including alternative splicing, that allow them to withstand this stress. However, how alternative splicing contributes to heat stress responses in wheat (Triticum aestivum) is unclear.

We reveal that the heat shock transcription factor gene TaHSFA6e is alternatively spliced in response to heat stress. TaHSFA6e generates two major functional transcripts: TaHSFA6e‐II and TaHSFA6e‐III. TaHSFA6e‐III enhances the transcriptional activity of three downstream heat shock protein 70 (TaHSP70) genes to a greater extent than does TaHSFA6e‐II. Further investigation reveals that the enhanced transcriptional activity of TaHSFA6e‐III is due to a 14‐amino acid peptide at its C‐terminus, which arises from alternative splicing and is predicted to form an amphipathic helix.

Results show that knockout of TaHSFA6e or TaHSP70s increases heat sensitivity in wheat. Moreover, TaHSP70s are localized in stress granule following exposure to heat stress and are involved in regulating stress granule disassembly and translation re‐initiation upon stress relief. Polysome profiling analysis confirms that the translational efficiency of stress granule stored mRNAs is lower at the recovery stage in Tahsp70s mutants than in the wild types.

Our finding provides insight into the molecular mechanisms by which alternative splicing improves the thermotolerance in wheat.
Learning Curve and Clinical Outcomes of Ultrasonic Osteotome‐based En Bloc Laminectomy for Thoracic Ossification of the Ligamentum Flavum
Authors: Hu Yuanyu , Dong Yanlei , Qi Junbo , Chen Zhongqiang , Li Weishi , Tian Yun , Sun Chuiguo
Published: July 2023

Objective

Despite rapid advances in minimally invasive surgery, en bloc laminectomy remains the most common surgical approach for treating thoracic ossification of the ligamentum flavum (TOLF). However, the learning curve of this risky operation is rarely reported. Therefore, we aimed to describe and analyze the learning curve of ultrasonic osteotome‐based en bloc laminectomy for TOLF.

Methods

Among 151 consecutive patients with TOLF who underwent en bloc laminectomy performed by one surgeon between January 2012 and December 2017, we retrospectively analyzed their demographic data, surgical parameters, and neurological function. Neurological outcome was evaluated with the modified Japanese Orthopaedic Association (mJOA) scale, and the Hirabayashi method was used to calculate the neurological recovery rate. The learning curve was assessed with logarithmic curve‐fitting regression analysis. Univariate analysis methods were used for statistical analysis, including t‐test, rank sum test, and chi‐square test.

Results

A total of 50% of learning milestones could be reached in approximately 14 cases, and the asymptote in 76 cases. Therefore, 76 of the 151 enrolled patients were defined as the “early group,” and the remaining 75 were delimitated as the “late group” for comparison. There was a significant intergroup difference in the corrected operative time (94.80 ± 27.77 vs 65.93 ± 15.67 min, P < 0.001) and the estimated blood loss (median 240 vs 400 mL, P < 0.001). The overall follow‐up was 83.1 ± 18.5 months. The mJOA significantly increased from a median of 5 (IQR: 4–5) before the surgery to 10 (IQR: 9–10) at the last follow‐up (P < 0.001). The overall complication rate was 37.1%, and no significant intergroup difference was found, except for the incidence of dural tears (31.6% vs 17.3%, p = 0.042).

Conclusion

Initially, mastering the en bloc laminectomy technique using ultrasonic osteotome for TOLF treatment can be challenging, but the surgeon's experience improves as the operative time and blood loss decrease. Improved surgical experience reduced the risk of dural tears but was not associated with the overall complication rate or long‐term neurological function. Despite the relatively long learning curve, en bloc laminectomy is a secure and valid technique for TOLF treatment.
Inclusive growth in the face of increasing urbanization: What experience for African countries?
Authors: Ngounou Borice Augustin , Tekam Oumbe Honoré , Ongo Nkoa Bruno Emmanuel , Noubissi Domguia Edmond
Published: July 2023

Urbanization and inclusive growth in Africa are very closely linked, and the literature is extremely fertile. The objective of this paper is to determine the effects of urbanization on inclusive growth in a sample of 48 African countries. We specify and estimate respectively a panel data model, fixed effects, Driscoll and Kraay, generalized least squares, robustness via Lewbel two‐stage least squares, and system generalized method of moments over the period 1995–2020. Our results show that urbanization significantly and statistically improves inclusive growth in Africa. We obtain the same result for each regional area (North Africa, West Africa, East Africa, and Central Africa) except for Southern Africa where we find that urbanization rather contributes to worsening inclusive growth. We propose that African policymakers take advantage of current urbanization patterns to effectively plan, manage and deliver U infrastructure technology services such as transport and ICT infrastructure. This will enable the growing population moving from underdeveloped regions to urban centers to access better services and employment opportunities, thereby contributing to economic progress.
Secular trends in the physical fitness of Brazilian youth: Evidence that fitness is declining for the majority but not for a fit minority
Authors: Nevill Alan M. , Duncan Michael J. , Gaya Adroaldo , Mello Júlio B.
Published: July 2023

Background

There has been a decline in children's physical fitness in recent decades. Such concerns are largely based on evidence from North America, Europe, and Asia. The current study describes the secular trend and variation (spread) in the physical fitness scores of young Brazilians from 2005 to 2022.

Methods

This study is a repeated, cross‐sectional surveillance study (1999–2022). Children and adolescents (n = 65 139; boys = 36 539) participated between 2005 and 2022. In each cohort six physical fitness tests were conducted: (1) 20‐m sprint speed (m s−1), (2) cardio‐respiratory 6‐min run test (m min−1), (3) abdominal strength test (sit‐ups per min), (4) horizontal jump test (cm), (5) the agility test (m s−1), and (6) the medicine ball throw test (cm). Means and distributional characteristics of the population were assessed using ANOVA, ANCOVA adopting BMI as the body‐size covariate, Levene's test of equality‐of‐error variances, and Box and whisker plots.

Results

ANOVAs and ANCOVA's identified significant declines in physical fitness over time/year in 5 of the 6 physical fitness variables (e.g., 20‐m sprint speed slope B = −0.018 (m s−1 y−1); 95% CI −0.019 to −0.017; p < 0.001), the only exception being the medicine ball throw test (cm). The Levene's test of equality‐of‐error variances also identified a systematic increase in the variances/standard deviations over time/years.

Conclusions

Results provide powerful evidence that children and adolescents' physical fitness is declining, a trend that is also diverging asymmetrically, becoming more extreme in more recent years. The “fit” appear to be getting fitter, but the fitness of the “less‐fit” appears to be declining further. These results have important implications for sports medicine and government policy makers.