bluuebunny/crossref_metadata_2025 huggingface dataset:
Variation of Helicoverpa armigera symbionts across developmental stages and geographic locations
Authors: Zhao Chenchen , Wang Li , Zhang Kaixin , Zhu Xiangzhen , Li Dongyang , Ji Jichao , Luo Junyu , Cui Jinjie
Published: September 2023

Cotton bollworm (Helicoverpa armigera) poses a global problem, causing substantial economic and ecological losses. Endosymbionts in insects play crucial roles in multiple insect biological processes. However, the interactions between H. armigera and its symbionts have not been well characterized to date. We investigated the symbionts of H. armigera in the whole life cycle from different geographical locations. In the whole life cycle of H. armigera, Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria were the dominant bacteria at the phylum level, while Enterococcus, Enterobacter, Glutamicibacter, and Bacillus were the four dominant bacteria at the genus level. Furthermore, high similarity in symbiotic bacterial community was observed in different stages of H. armigera, which were dominated by Enterococcus and Enterobacter. In fields, the dominant bacteria were Proteobacteria and Bacteroidetes, whereas, in the laboratory, the dominant bacteria were Proteobacteria. At the genus level, the dominant bacteria in cotton bollworm eggs of wild populations were Enterobacter, Morganella, Lactococcus, Asaia, Apibacter, and Enterococcus, and the subdominant bacteria were Bartonella, Pseudomonas, and Orbus. Moreover, the symbionts varied with geographical locations, and the closer the geographical distance, the more similar the microbial composition. Taken together, our study identifies and compares the symbiont variation along with geographical gradients and host development dynamic and reveals the high flexibility of microbiome communities in H. armigera, which probably benefits for the successful survival in a complicated changing environment.
Research progress of diabetic retinopathy and gut microecology
Authors: Wang Rui , Wang Qiu-Yuan , Bai Yang , Bi Ye-Ge , Cai Shan-Jun
Published: September 2023

According to the prediction of the International Diabetes Federation, global diabetes mellitus (DM) patients will reach 783.2 million in 2045. The increasing incidence of DM has led to a global epidemic of diabetic retinopathy (DR). DR is a common microvascular complication of DM, which has a significant impact on the vision of working-age people and is one of the main causes of blindness worldwide. Substantial research has highlighted that microangiopathy and chronic low-grade inflammation are widespread in the retina of DR. Meanwhile, with the introduction of the gut-retina axis, it has also been found that DR is associated with gut microecological disorders. The disordered structure of the GM and the destruction of the gut barrier result in the release of abnormal GM flora metabolites into the blood circulation. In addition, this process induced alterations in the expression of various cytokines and proteins, which further modulate the inflammatory microenvironment, vascular damage, oxidative stress, and immune levels within the retina. Such alterations led to the development of DR. In this review, we discuss the corresponding alterations in the structure of the GM flora and its metabolites in DR, with a more detailed focus on the mechanism of gut microecology in DR. Finally, we summarize the potential therapeutic approaches of DM/DR, mainly regulating the disturbed gut microecology to restore the homeostatic level, to provide a new perspective on the prevention, monitoring, and treatment of DR.
Identification of ARF transcription factor gene family and its defense responses to bacterial infection and salicylic acid treatment in sugarcane
Authors: Lin Jia-Xin , Ali Ahmad , Chu Na , Fu Hua-Ying , Huang Mei-Ting , Mbuya Sylvain Ntambo , Gao San-Ji , Zhang Hui-Li
Published: September 2023

Auxin response factor (ARF) is a critical regulator in the auxin signaling pathway, involved in a variety of plant biological processes. Here, gene members of 24 SpapARFs and 39 SpnpARFs were identified in two genomes of Saccharum spontaneum clones AP85-441 and Np-X, respectively. Phylogenetic analysis showed that all ARF genes were clustered into four clades, which is identical to those ARF genes in maize (Zea mays) and sorghum (Sorghum bicolor). The gene structure and domain composition of this ARF family are conserved to a large degree across plant species. The SpapARF and SpnpARF genes were unevenly distributed on chromosomes 1–8 and 1–10 in the two genomes of AP85-441 and Np-X, respectively. Segmental duplication events may also contribute to this gene family expansion in S. spontaneum. The post-transcriptional regulation of ARF genes likely involves sugarcane against various stressors through a miRNA-medicated pathway. Expression levels of six representative ShARF genes were analyzed by qRT-PCR assays on two sugarcane cultivars [LCP85-384 (resistant to leaf scald) and ROC20 (susceptible to leaf scald)] triggered by Acidovorax avenae subsp. avenae (Aaa) and Xanthomonas albilineans (Xa) infections and salicylic acid (SA) treatment. ShARF04 functioned as a positive regulator under Xa and Aaa stress, whereas it was a negative regulator under SA treatment. ShARF07/17 genes played positive roles against both pathogenic bacteria and SA stresses. Additionally, ShARF22 was negatively modulated by Xa and Aaa stimuli in both cultivars, particularly LCP85-384. These findings imply that sugarcane ARFs exhibit functional redundancy and divergence against stressful conditions. This work lays the foundation for further research on ARF gene functions in sugarcane against diverse environmental stressors.
Menopausal hormone therapy and risk of dementia: health insurance database in South Korea-based retrospective cohort study
Authors: Yuk Jin-Sung , Lee Jin San , Park Joong Hyun
Published: September 2023

Introduction

Menopausal hormone therapy (MHT) is used to alleviate the symptoms associated with menopause, despite the lack of recommendations for MHT in preventing dementia. Recent nationwide studies have explored the association between MHT and dementia risk, but the findings remain limited. This study aims to investigate the association between MHT and the incidence of Alzheimer’s disease (AD) and non-AD dementia using national population data from Korea.

Methods

We conducted a retrospective study using data from the National Health Insurance Service in Korea between January 1, 2002, and December 31, 2019. Women over 40 years were eligible for this study and classified into the MHT or non-MHT groups. The MHT group consisted of women who used Tibolone (TIB), combined estrogen plus progestin by the manufacturer (CEPM), estrogen, combined estrogen plus progestin by a physician (CEPP), and transdermal estrogen during menopause. We compared the risk of dementia between the MHT and non-MHT groups.

Results

The study included 1,399,256 patients, of whom 387,477 were in the MHT group, and 1,011,779 were in the non-MHT group. The median duration of MHT was 23 months (range: 10–55 months). After adjusting for available confounders, we found that different types of MHT had varying effects on the occurrence of dementia. TIB (HR 1.041, 95% confidence interval (CI) 1.01–1.072) and oral estrogen alone (HR 1.081, 95% CI 1.03–1.134) were associated with a higher risk of AD dementia. In contrast, there was no difference in the risk of AD dementia by CEPM (HR 0.975, 95% CI 0.93–1.019), CEPP (HR 1.131, 95% CI 0.997–1.283), and transdermal estrogen (HR 0.989, 95% CI 0.757–1.292) use. The use of TIB, CEPM, and oral estrogen alone increased the risk of non-AD dementia (HR 1.335, 95% CI 1.303–1.368; HR 1.25, 95% CI 1.21–1.292; and HR 1.128, 95% CI 1.079–1.179; respectively), but there was no risk of non-AD dementia in the other MHT groups (CEPP and topical estrogen).

Conclusion

Our findings indicate that MHT has varying effects on the incidence of AD and non-AD dementia. Specifically, TIB, CEPM, and oral estrogen alone increase the risk of non-AD dementia, while transdermal estrogen is not associated with dementia risk. It is essential to consider the type of MHT used when assessing the risk of dementia in women.
Disparity of smell tests in Alzheimer’s disease and other neurodegenerative disorders: a systematic review and meta-analysis
Authors: Liu Silin , Jiang Zhihui , Zhao Jing , Li Zhensheng , Li Ruixin , Qiu Yunyi , Peng Hua
Published: September 2023

Background

There are discrepancies of olfactory impairment between Alzheimer’s disease (AD) and other neurodegenerative disorders. Olfactory deficits may be a potential marker for early and differential diagnosis of AD. We aimed to assess olfactory functions in patients with AD and other neurodegenerative disorders, to further evaluate the smell tests using subgroup analysis, and to explore moderating factors affecting olfactory performance.

Methods

Cross-sectional studies relating to olfactory assessment for both AD and other neurodegenerative disorders published before 27 July 2022 in English, were searched on PubMed, Embase and Cochrane. After literature screening and quality assessment, meta-analyses were conducted using stata14.0 software.

Results

Forty-two articles involving 12 smell tests that evaluated 2,569 AD patients were included. It was revealed that smell tests could distinguish AD from mild cognitive impairment (MCI), Lewy body disease (LBD), depression, and vascular dementia (VaD), but not from diseases such as frontotemporal dementia (FTD). Our finding indicated that in discriminating AD from MCI, the University of Pennsylvania Smell Identification Test (UPSIT) was most frequently used (95%CI: −1.12 to −0.89), while the Brief Smell Identification Test (B-SIT), was the most widely used method in AD vs. LBD group. Further subgroup analyses indicated that the methods of smell test used contributed to the heterogeneity in olfactory threshold and discrimination scores in group AD vs. MCI. While the moderating variables including age, MMSE scores, education years in AD vs. LBD, were account for heterogeneity across studies.

Conclusion

Our finding suggests smell tests have potential value in early differential diagnosis of AD. UPSIT and its simplified variant, B-SIT, are widely used methods in the analyses.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php? RecordID = 357970 (PROSPERO, registration number CRD42022357970).
Dual production of polyhydroxyalkanoates and antibacterial/antiviral gold nanoparticles
Authors: Paxinou Alexandra , Marcello Elena , Vecchiato Vittoria , Erman Lara , Wright Edward , Noble Brendon , McCormick Adele , Basnett Pooja
Published: September 2023

Gold nanoparticles (AuNPs) have been explored for their use in medicine. Here, we report a sustainable, and cost-effective method to produce AuNPs using a bacterial strain such as Pseudomonas mendocina CH50 which is also known to be a polyhydroxyalkanoate (PHA) producer. A cell-free bacterial supernatant, which is typically discarded after PHA extraction, was used to produce spherical AuNPs of 3.5 ± 1.5 nm in size as determined by Transmission Electron Microscopy (TEM) analysis. The AuNPs/PHA composite coating demonstrated antibacterial activity against Staphylococcus aureus 6538P, and antiviral activity, with a 75% reduction in viral infectivity against SARS-CoV-2 pseudotype virus.
HSP27 induced glaucomatous damage in mice of young and advanced age
Authors: Erb Clivia , Reinehr Sabrina , Theiss Carsten , Dick H. Burkhard , Joachim Stephanie C.
Published: September 2023

Introduction

Age-related diseases such as glaucoma, a leading cause of blindness, are having an upward trend due to an aging society. In glaucoma, some patients display altered antibody profiles and increased antibody titers, for example against heat shock protein 27 (HSP27). An intravitreal injection of HSP27 leads to glaucoma-like damage in rats. We now aimed to investigate if aged mice are more prone to this damage than younger ones.

Methods

We intravitreally injected HSP27 into young (1–2 months) and aged (7–8 months) mice to compare glaucomatous damage. Respective age-matched controls received PBS. Not injected eyes served as naive controls.

Results

Optical coherence tomography 4 weeks after injection showed no changes in retinal thickness in all groups at both ages. Cell counts and RT-qPCR revealed a significant reduction in RGC numbers in HSP27 mice at both ages. Comparing aged and young HSP27 mice, no differences in Rbpms and Pou4f1 (RGCs) expression was detected, while the Tubb3 expression (neuronal cells) was significantly upregulated in aged HSP27 animals. Neither microglia/macrophages nor (resident) microglia counts revealed significant differences in HSP27 mice at both ages. Nevertheless, increased relative Iba1 and Tmem119 expression was detected in young and aged HSP27 mice. Aged HSP27 mice displayed a significantly lower Iba1 expression than young ones, whereas Cd68 levels were upregulated. A larger GFAP+ area and an upregulation of GFAP expression in HSP27 animals of both ages indicated a macrogliosis. Also, elevated Il1b and Nos2 expression levels were observed in young and aged HSP27 mice. However, only Il1b levels were upregulated when comparing 7–8 months to 1–2 months old animals. A larger HSP25+ area was seen in aged HSP27 animals, while Hspb2 expression levels were downregulated in both HSP27 groups. The aged HSP27 group displayed an upregulated Hspb2 expression compared to young mice. Furthermore, a higher optic nerve degeneration score was noted in young and aged HSP27 groups.

Discussion

These findings indicate that an intravitreal injection of HSP27 led to RGC loss accompanied by inflammation. Age-dependent effects (7–8 months vs. 1–2 months) were not very prominent. The results suggest a potential role of extracellular HSP27 in the development of glaucoma.
Influence of voluntary action and outcome valence on the sense of agency
Authors: Niu Nana , Wu Yun , Li Hui'e , Li Mei , Yang Danping , Fan Wei , Zhong Yiping
Published: September 2023

Recent studies have revealed that people might experience a lessened sense of agency for negative consequences by claiming that they were obeying orders. However, little is known about the cognitive neural mechanism behind the reduced sense of agency when individuals are forced to inflict physical harm on others. This study adopted temporal estimation tasks to investigate the internal mechanism of voluntary action on the sense of agency and the moderating effect of outcome valence as measured by event-related potentials (ERPs). In the temporal estimation task, participants were asked to make trade-offs of monetary gains for themselves against painful electric stimuli experienced by strangers, subjectively estimated the perceptual temporal interval between keypress actions (i.e., free or coercive actions) and consequent outcomes (i.e., positive or negative tones) and rated the feeling of control. The results showed that perceived temporal interval was shorter for positive tones compared with negative tones in the coercive condition, and induced more negative N1 and N300 amplitudes, which indicated that the implicit sense of agency was higher. However, the explicit sense of agency was stronger in the free condition than in the coercive condition, which was not influenced by outcome valence. We discuss the implications of utilizing positive feedback and free choice as significant strategies for those experiencing the abnormal sense of agency.
Harnessing acoustic speech parameters to decipher amyloid status in individuals with mild cognitive impairment
Authors: García-Gutiérrez Fernando , Marquié Marta , Muñoz Nathalia , Alegret Montserrat , Cano Amanda , de Rojas Itziar , García-González Pablo , Olivé Clàudia , Puerta Raquel , Orellana Adelina , Montrreal Laura , Pytel Vanesa , Ricciardi Mario , Zaldua Carla , Gabirondo Peru , Hinzen Wolfram , Lleonart Núria , García-Sánchez Ainhoa , Tárraga Lluís , Ruiz Agustín , Boada Mercè , Valero Sergi
Published: September 2023

Alzheimer's disease (AD) is a neurodegenerative condition characterized by a gradual decline in cognitive functions. Currently, there are no effective treatments for AD, underscoring the importance of identifying individuals in the preclinical stages of mild cognitive impairment (MCI) to enable early interventions. Among the neuropathological events associated with the onset of the disease is the accumulation of amyloid protein in the brain, which correlates with decreased levels of Aβ42 peptide in the cerebrospinal fluid (CSF). Consequently, the development of non-invasive, low-cost, and easy-to-administer proxies for detecting Aβ42 positivity in CSF becomes particularly valuable. A promising approach to achieve this is spontaneous speech analysis, which combined with machine learning (ML) techniques, has proven highly useful in AD. In this study, we examined the relationship between amyloid status in CSF and acoustic features derived from the description of the Cookie Theft picture in MCI patients from a memory clinic. The cohort consisted of fifty-two patients with MCI (mean age 73 years, 65% female, and 57% positive amyloid status). Eighty-eight acoustic parameters were extracted from voice recordings using the extended Geneva Minimalistic Acoustic Parameter Set (eGeMAPS), and several ML models were used to classify the amyloid status. Furthermore, interpretability techniques were employed to examine the influence of input variables on the determination of amyloid-positive status. The best model, based on acoustic variables, achieved an accuracy of 75% with an area under the curve (AUC) of 0.79 in the prediction of amyloid status evaluated by bootstrapping and Leave-One-Out Cross Validation (LOOCV), outperforming conventional neuropsychological tests (AUC = 0.66). Our results showed that the automated analysis of voice recordings derived from spontaneous speech tests offers valuable insights into AD biomarkers during the preclinical stages. These findings introduce novel possibilities for the use of digital biomarkers to identify subjects at high risk of developing AD.
A scoping review of physiological biomarkers in autism
Authors: Shan Jiatong , Gu Yunhao , Zhang Jie , Hu Xiaoqing , Wu Haiyan , Yuan Tifei , Zhao Di
Published: September 2023

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by pervasive deficits in social interaction, communication impairments, and the presence of restricted and repetitive behaviors. This complex disorder is a significant public health concern due to its escalating incidence and detrimental impact on quality of life. Currently, extensive investigations are underway to identify prospective susceptibility or predictive biomarkers, employing a physiological biomarker-based framework. However, knowledge regarding physiological biomarkers in relation to Autism is sparse. We performed a scoping review to explore putative changes in physiological activities associated with behaviors in individuals with Autism. We identified studies published between January 2000 and June 2023 from online databases, and searched keywords included electroencephalography (EEG), magnetoencephalography (MEG), electrodermal activity markers (EDA), eye-tracking markers. We specifically detected social-related symptoms such as impaired social communication in ASD patients. Our results indicated that the EEG/ERP N170 signal has undergone the most rigorous testing as a potential biomarker, showing promise in identifying subgroups within ASD and displaying potential as an indicator of treatment response. By gathering current data from various physiological biomarkers, we can obtain a comprehensive understanding of the physiological profiles of individuals with ASD, offering potential for subgrouping and targeted intervention strategies.
The role of prostate-specific antigen in the osteoblastic bone metastasis of prostate cancer: a literature review
Authors: Zhang Xu , Jiang Peng , Wang Chaojun
Published: September 2023

Prostate cancer is the only human malignancy that generates predominantly osteoblastic bone metastases, and osteoblastic bone metastases account for more than 90% of osseous metastases of prostate cancer. Prostate-specific antigen (PSA) plays an important role in the osteoblastic bone metastasis of prostate cancer, which can promote osteomimicry of prostate cancer cells, suppress osteoclast differentiation, and facilitate osteoblast proliferation and activation at metastatic sites. In the meantime, it can activate osteogenic factors, including insulin-like growth factor, transforming growth factor β2 and urokinase-type plasminogen activator, and meanwhile suppress osteolytic factors such as parathyroid hormone-related protein. To recapitulate, PSA plays a significant role in the osteoblastic predominance of prostate cancer bone metastasis and bone remodeling by regulating multiple cells and factors involved in osseous metastasis.
Pertinence of glioma and single nucleotide polymorphism of TERT, CCDC26, CDKN2A/B and RTEL1 genes in glioma: a meta-analysis
Authors: Wu Yaqi , Zhou Jun , Zhang Jun , Tang Zhijian , Chen Xi , Huang Lulu , Liu Shengwen , Chen Hong , Wang Yu
Published: September 2023

Background

Previous genetic-epidemiological studies considered TERT (rs2736100), CCDC26 (rs4295627), CDKN2A/B (rs4977756) and RTEL1 (rs6010620) gene polymorphisms as the risk factors specific to glioma. However, the data samples of previous genetic-epidemiological studies are modest to determine whether they have definite association with glioma.

Method

The study paid attention to systematically searching databases of PubMed, Embase, Web of Science (WoS), Scopus, Cochrane Library and Google Scholars. Meta-analysis under 5 genetic models, namely recessive model (RM), over-dominant model (O-DM), allele model (AM), co-dominant model (C-DM) and dominant model (DM) was conducted for generating odds ratios (ORs) and 95% confidence intervals (CIs). That was accompanied by subgroup analyses according to various racial groups. The software STATA 17.0 MP was implemented in the study.

Result

21 articles were collected. According to data analysis results, in four genetic models (AM, RM, DM and C-DM) TERT gene rs2736100 polymorphism, CCDC26 gene rs4295627 polymorphism, CDKN2A/B gene rs4977756 polymorphism and RTEL1 gene rs6010620 polymorphisms increased the risk of glioma in Caucasians to different degrees. In Asian populations, the CCDC26 gene rs4295627 polymorphism and CDKN2A/B gene rs4977756 polymorphism did not exhibit a relevance to the risk of glioma. It is suggested to cautiously explain these results as the sample size is small.

Conclusion

The current meta-analysis suggested that the SNP of TERT (rs2736100), CCDC26 (rs4295627), CDKN2A/B (rs4977756) and RTEL1 (rs6010620) genes in glioma might increase risk of glioma, but there are ethnic differences. Further studies evaluating these polymorphisms and glioma risk are warranted.
Development of an in vivo murine model of perineural invasion and spread of cutaneous squamous cell carcinoma of the head and neck
Authors: de Lima Priscila O. , Broit Natasa , Huang Johnson D. , Lim Jae H. , Gardiner Damien J. , Brown Ian S. , Panizza Benedict J. , Boyle Glen M. , Simpson Fiona
Published: September 2023

Introduction

Cutaneous squamous cell carcinoma of the head and neck (cSCCHN) can metastasize by invading nerves and spread toward the central nervous system. This metastatic process is called perineural invasion (PNI) and spread (PNS). An in vivo sciatic nerve mouse model is used for cSCCHN PNI/PNS. Here we describe a complementary whisker pad model which allows for molecular studies investigating drivers of PNI/PNS in the head and neck environment.

Methods

A431 cells were injected into the whisker pads of BALB/c Foxn1nu and NSG-A2 mice. Tumor progression was monitored by bioluminescence imaging and primary tumor resection was performed. PNI was detected by H&E and IHC. Tumor growth and PNI were assessed with inducible ablation of LOXL2.

Results

The rate of PNI development in mice was 10%-28.6%. Tumors exhibited PNI/PNS reminiscent of the morphology seen in the human disease. Our model’s utility was demonstrated with inducible ablation of LOXL2 reducing primary tumor growth and PNI.

Discussion

This model consists in a feasible way to test molecular characteristics and potential therapies, offers to close a gap in the described in vivo methods for PNI/PNS of cSCCHN and has uses in concert with the established sciatic nerve model.
Targeting chemoresistance and mitochondria-dependent metabolic reprogramming in acute myeloid leukemia
Authors: Feng Lili , Zhang Philip Y. , Gao Wenda , Yu Jinming , Robson Simon C.
Published: September 2023

Chemoresistance often complicates the management of cancer, as noted in the instance of acute myeloid leukemia (AML). Mitochondrial function is considered important for the viability of AML blasts and appears to also modulate chemoresistance. As mitochondrial metabolism is aberrant in AML, any distinct pathways could be directly targeted to impact both cell viability and chemoresistance. Therefore, identifying and targeting those precise rogue elements of mitochondrial metabolism could be a valid therapeutic strategy in leukemia. Here, we review the evidence for abnormalities in mitochondria metabolic processes in AML cells, that likely impact chemoresistance. We further address several therapeutic approaches targeting isocitrate dehydrogenase 2 (IDH2), CD39, nicotinamide phosphoribosyl transferase (NAMPT), electron transport chain (ETC) complex in AML and also consider the roles of mesenchymal stromal cells. We propose the term “mitotherapy” to collectively refer to such regimens that attempt to override mitochondria-mediated metabolic reprogramming, as used by cancer cells. Mounting evidence suggests that mitotherapy could provide a complementary strategy to overcome chemoresistance in liquid cancers, as well as in solid tumors.
Association between marijuana use and kidney stone: a cross-sectional study of NHANES 2009 to 2018
Authors: Di Xingpeng , Xiang Liyuan , Wang Menghua , Wei Xin
Published: September 2023

Objective: The purpose of this investigation is to determine whether regular marijuana use is related to history of kidney stones in the US population.

Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2018. Kidney stone and marijuana use data were collected from self-report questionnaires. Multivariate logistic regression and multiple sensitivity analyses were applied to examine the relationship between marijuana usage and kidney stones.

Results: There are approximately 26.04% of the US population have admitted to using marijuana in their lifetime. Compared with none regular users, those with a higher frequency of marijuana use were more males, more non-Hispanic races, lower than high school education, overweight, no recreational activity, without diabetes mellitus, and more coronary heart disease. After adjusting for potential confounders, multivariate regression analysis demonstrated that marijuana use was inversely correlated to kidney stones in males (Odds ratio [OR] = 0.72, 95% Confidence interval [CI] = 0.54–0.97). One to seven times/week regular consumption of marijuana was associated with kidney stones in males (OR = 0.62, 95% CI = 0.43–0.89). Sensitivity analyses validated the robustness of our outcomes.

Conclusion: Our findings revealed that regular marijuana male users were inversely associated with kidney stones. Marijuana use one to six times/week was inversely related to the risk of kidney stones in males. Further studies are required to explore the dose and type associations of marijuana with kidney stones.
The participation of clinical pharmacists in the treatment of patients with central nervous system infection can improve the effectiveness and appropriateness of anti-infective treatments: a retrospective cohort study
Authors: Cheng Jie , Dang ChuanDong , Li Xiao , Wang JianJun , Huang Xin , Li Yan , Cui XueYan
Published: September 2023

Background: Central nervous system infection (CNSI) treatment in hospital neurosurgery emphasizes the importance of optimizing antimicrobial therapy. Timely and appropriate empiric antibiotic treatment is critical for managing patients with bacterial meningitis.

Objectives: To evaluate the activities of clinical pharmacists in the anti-infective treatment of patients with CNSI in neurosurgery.

Method: A single-center retrospective cohort study was carried out from January 2021 to March 2023 at a tertiary teaching hospital in China. The study sample included a group that received pharmacy services and a group that did not. In the pharmacy services group, the anti-infective treatment plan was led and developed by pharmacists. Pharmaceutical care, including medication therapy and all CNSI treatment regimens, was administered in daily unit rounds by pharmacists. Baseline demographics, treatment outcomes, and rational use of antibiotics were compared between the two groups, and the impact of a antimicrobial stewardship (AMS) program was evaluated.

Results: Of the 306 patients assessed according to the inclusion and exclusion criteria, 151 patients were included, and 155 patients were excluded due to abnormal data and missing information on antibiotic costs or antimicrobial use. Eventually, 73 were included in the pharmacy services group and 78 in the group without pharmacist participation. The antibiotic use density (AUD) of the pharmacy services group decreased from 167.68 to 127.63 compared to the group without pharmacist participation. After the pharmacist services, the AUD for linezolid decreased from 9.15% to 5.23% and that for miscellaneous agents decreased from 17.91% to 6.72%. The pharmacy services group had better improvement (p < 0.05) and a significantly higher score for the rational use of antibiotics (p < 0.05) than the group without pharmacist participation.

Conclusion: The clinical pharmacist services evaluation results demonstrated an essential role of clinical pharmacist-led AMS programs in the effective and appropriate use of anti-infective treatments in neurosurgery with patients with CNSI.
Accelerated high fluence photoactivated chromophore for infectious keratitis—corneal cross-linking (PACK-CXL) at the slit lamp: a pilot study
Authors: Olshaker Hagar , Achiron Asaf , Chorny Alexander , Hafezi Farhad , Yahalomi Tal , Kratz Assaf , Tsumi Erez , Lu Nan-Ji , Knyazer Boris
Published: September 2023

Introduction: Photoactivated Chromophore for Infectious Keratitis-Corneal Cross-Linking (PACK-CXL) has garnered substantial interest among researchers and ophthalmologists due to its high promise as a potential treatment for infectious keratitis. The aim of this study is to evaluate the efficacy and safety of high fluence PACK-CXL, using 10.0 J/cm2 (30 mW/cm2, 5 min, and 33 s) at the slit lamp.

Methods: This prospective interventional, nonrandomized cohort study included 20 eyes of 20 patients with bacterial, fungal, or mixed origin keratitis who underwent high fluence PACK-CXL treatment as an adjunct therapy to conventional antimicrobial therapy per American Academy of Ophthalmology treatment guidelines. The re-epithelization time was recorded, and corneal endothelial cell density was counted before and after treatment.

Results: The average re-epithelization time was 8.2 ± 2.8 days (range 3–14 days). After PACK-CXL treatment, eight patients (40%) were directly discharged, while the remained patients stayed in the hospital for an average of 5.6 ± 3.5 days. No eyes required keratoplasty. Endothelial cell density counts before and after the PACK-CXL procedure were 2,562.1 ± 397.3, and 2,564.8 ± 404.5 cells/mm2, respectively (p = 0.96).

Conclusion: although it was not a randomized control trial, we conclude that high fluence PACK-CXL as an adjuvant therapy is safe with no complications observed, and efficient as time to re-epithelization was less than 14 days for all patients and no patients underwent tectonic keratoplasties. Further research is needed to compare it to the current standard of care.
Drug repurposing for Alzheimer’s disease from 2012–2022—a 10-year literature review
Authors: Grabowska Monika E. , Huang Annabelle , Wen Zhexing , Li Bingshan , Wei Wei-Qi
Published: September 2023

Background: Alzheimer’s disease (AD) is a debilitating neurodegenerative condition with few treatment options available. Drug repurposing studies have sought to identify existing drugs that could be repositioned to treat AD; however, the effectiveness of drug repurposing for AD remains unclear. This review systematically analyzes the progress made in drug repurposing for AD throughout the last decade, summarizing the suggested drug candidates and analyzing changes in the repurposing strategies used over time. We also examine the different types of data that have been leveraged to validate suggested drug repurposing candidates for AD, which to our knowledge has not been previous investigated, although this information may be especially useful in appraising the potential of suggested drug repurposing candidates. We ultimately hope to gain insight into the suggested drugs representing the most promising repurposing candidates for AD.

Methods: We queried the PubMed database for AD drug repurposing studies published between 2012 and 2022. 124 articles were reviewed. We used RxNorm to standardize drug names across the reviewed studies, map drugs to their constituent ingredients, and identify prescribable drugs. We used the Anatomical Therapeutic Chemical (ATC) Classification System to group drugs.

Results: 573 unique drugs were proposed for repurposing in AD over the last 10 years. These suggested repurposing candidates included drugs acting on the nervous system (17%), antineoplastic and immunomodulating agents (16%), and drugs acting on the cardiovascular system (12%). Clozapine, a second-generation antipsychotic medication, was the most frequently suggested repurposing candidate (N = 6). 61% (76/124) of the reviewed studies performed a validation, yet only 4% (5/124) used real-world data for validation.

Conclusion: A large number of potential drug repurposing candidates for AD has accumulated over the last decade. However, among these drugs, no single drug has emerged as the top candidate, making it difficult to establish research priorities. Validation of drug repurposing hypotheses is inconsistently performed, and real-world data has been critically underutilized for validation. Given the urgent need for new AD therapies, the utility of real-world data in accelerating identification of high-priority candidates for AD repurposing warrants further investigation.
Pharmacokinetics and safety of highly variable valsartan in single-pill combination with amlodipine versus its generic formulation: a randomized, three-cycle, three-sequence, partially replicated crossover phase I bioequivalence clinical trial
Authors: Qiu Bo , Song Haojing , Ding Congyang , Sun Xue , Du Runxuan , Yang Haotian , Bai Wanjun , Dong Zhanjun
Published: September 2023

Valsartan/amlodipine (I) is a single-pill combination (SPC) of an angiotensin II receptor blocker (ARB) and a calcium channel blocker (CCB) for treating hypertension. A clinical trial was performed to demonstrate that the test and reference valsartan/amlodipine formulations were bioequivalent under fasting and postprandial conditions. Participants were randomly divided into three sequences at a ratio of 1:1:1 for three-cycle, reference formulation replicated, crossover administration. The average bioequivalence (ABE) and reference-scaled average bioequivalence (RSABE) methods were used to evaluate BE using the main pharmacokinetic (PK) parameters. Overall, 45 eligible participants were enrolled in the postprandial trial, which was consistent with the fasting trial. For valsartan, the RSABE method was used to evaluate the BE of Cmax, while the ABE method was applied to evaluate the BE of AUC0–t and AUC0–∞. Both point estimates and 95% upper confidence bound met the BE criteria. For amlodipine, the ABE method was performed, and the 90% confidence intervals of the geometric mean ratios (GMR) for Cmax and AUC0–72 h were all within 80%–125%, with the BE criteria being met. Therefore, the two formulations are bioequivalent and have similar safety profiles in healthy Chinese subjects.

Clinical trial registration: [http://www.chinadrugtrials.org.cn/index.html], identifier [CTR20210214].
Adding a low frequency limit to fractional wave propagation models
Authors: Holm Sverre , Chandrasekaran Sri Nivas , Näsholm Sven Peter
Published: September 2023

Power-law attenuation in elastic wave propagation of both compressional and shear waves can be described with multiple relaxation processes. It may be less physical to describe it with fractional calculus medium models, but this approach is useful for simulation and for parameterization where the underlying relaxation structure is very complex. It is easy to enforce a low-frequency limit on a relaxation distribution and this gives frequency squared characteristics for low frequencies which seems to fit some media in practice. Here the goal is to change the low-frequency behavior of fractional models also. This is done by tempering the relaxation moduli of the fractional Kelvin-Voigt and diffusion models with an exponential function and the effect is that the low-frequency attenuation will increase with frequency squared and the square root of frequency respectively. The time-space wave equations for the tempered models have also been found, and for this purpose the concept of the fractional pseudo-differential operator borrowed from the field of Cole-Davidson dielectrics is useful. The tempering does not remove the singularity in the relaxation moduli of the models, but this has only a minor effect on the solutions.
The effects of high-intensity interval training at the anaerobic and psychomotor fatigue thresholds on physiological parameters in young soccer players: a prospective study
Authors: Chmura Paweł , Chmura Jan , Chodor Wiktor , Drożdżowski Adrian , Rokita Andrzej , Konefał Marek
Published: September 2023

This study aimed to investigate the effects of a 4-week specific high-intensity interval training (HIIT) program performed between the anaerobic threshold (ANT) and the psychomotor fatigue threshold (PFT) on physiological parameters in 14 professional soccer players at the under-17 level. The first and second stages of the research protocol included a treadmill running exercise with increasing load and six 3-min four-versus-four games of soccer with a 3-min break between games. Players then participated in a training microcycle involving three specific HIIT exercises twice per week for 4 weeks, after which they repeated stages one and two, followed by an assessment of changes. The measurement of lactate (LA) determined ANT, whereas the choice reaction time (CRT) indicated PFT among other selected physiological parameters. The repeated-measure analysis of variance (ANOVA) compared mean values for the examined variables using Bonferroni post hoc test. It demonstrated significantly increased maximal oxygen consumption (VO2 max) from 45.9 ± 3.0 to 48.7 ± 2.6 at the ANT and from 49.1 ± 3.4 to 52.0 ± 3.6 on the PFT after 4 weeks of training. A significant increase in the running speed (RS) at both thresholds and heart rate (HR) at the ANT (p ≤ 0.05) was also recorded. Moreover, the players exceeded their intensity of effort during ANT while playing four-versus-four soccer matches, but they did not reach intensity during PFT. In conclusion, the findings of the study demonstrated that both thresholds shifted toward higher loads and the proposed specific HIIT effectively increased the exercise capacity of soccer players.
Seasonal variation in glucose and insulin is modulated by food and temperature conditions in a hibernating primate
Authors: Blanco Marina B. , Greene Lydia K. , Ellsaesser Laura N. , Williams Cathy V. , Ostrowski Catherine A. , Davison Megan M. , Welser Kay , Klopfer Peter H.
Published: September 2023

Feast-fast cycles allow animals to live in seasonal environments by promoting fat storage when food is plentiful and lipolysis when food is scarce. Fat-storing hibernators have mastered this cycle over a circannual schedule, by undergoing extreme fattening to stockpile fuel for the ensuing hibernation season. Insulin is intrinsic to carbohydrate and lipid metabolism and is central to regulating feast-fast cycles in mammalian hibernators. Here, we examine glucose and insulin dynamics across the feast-fast cycle in fat-tailed dwarf lemurs, the only obligate hibernator among primates. Unlike cold-adapted hibernators, dwarf lemurs inhabit tropical forests in Madagascar and hibernate under various temperature conditions. Using the captive colony at the Duke Lemur Center, we determined fasting glucose and insulin, and glucose tolerance, in dwarf lemurs across seasons. During the lean season, we maintained dwarf lemurs under stable warm, stable cold, or fluctuating ambient temperatures that variably included food provisioning or deprivation. Overall, we find that dwarf lemurs can show signatures of reversible, lean-season insulin resistance. During the fattening season prior to hibernation, dwarf lemurs had low glucose, insulin, and HOMA-IR despite consuming high-sugar diets. In the active season after hibernation, glucose, insulin, HOMA-IR, and glucose tolerance all increased, highlighting the metabolic processes at play during periods of weight gain versus weight loss. During the lean season, glucose remained low, but insulin and HOMA-IR increased, particularly in animals kept under warm conditions with daily food. Moreover, these lemurs had the greatest glucose intolerance in our study and had average HOMA-IR values consistent with insulin resistance (5.49), while those without food under cold (1.95) or fluctuating (1.17) temperatures did not. Remarkably low insulin in dwarf lemurs under fluctuating temperatures raises new questions about lipid metabolism when animals can passively warm and cool rather than undergo sporadic arousals. Our results underscore that seasonal changes in insulin and glucose tolerance are likely hallmarks of hibernating mammals. Because dwarf lemurs can hibernate under a range of conditions in captivity, they are an emerging model for primate metabolic flexibility with implications for human health.
Morphological and viscoelastic properties of the Achilles tendon in the forefoot, rearfoot strike runners, and non-runners in vivo
Authors: Zhang Xini , Deng Liqin , Xiao Songlin , Fu Weijie
Published: September 2023

The purpose of this study was to investigate the differences in the morphological and viscoelastic properties of the Achilles tendon (AT) among different groups (rearfoot strikers vs. forefoot strikers vs. non-runners). Thirty healthy men were recruited, including habitual forefoot strike runners (n = 10), rearfoot strike runners (n = 10), and individuals with no running habits (n = 10). The AT morphological properties (cross-sectional area and length) were captured by using an ultrasound device. The real-time ultrasound video of displacement changes at the medial head of the gastrocnemius and the AT junction during maximal voluntary isometric contraction and the plantar flexion moment of the ankle was obtained simultaneously by connecting the ultrasound device and isokinetic dynamometer via an external synchronisation box. The results indicated that male runners who habitually forefoot strike exhibited significantly lower AT hysteresis than male non-runners (p < 0.05). Furthermore, a greater peak AT force during maximal voluntary contraction was observed in forefoot strike male runners compared to that in male individuals with no running habits (p < 0.05). However, foot strike patterns were not related to AT properties in recreational male runners (p > 0.05). The lower AT hysteresis in male FFS runners implied that long-term forefoot strike patterns could enhance male-specific AT’s ability to store and release elastic energy efficiently during running, resulting in a more effective stretch-shortening cycle. The greater peak AT force in male FFS runners indicated a stronger Achilles tendon.
A two-step inverse solution for a single dipole cardiac source
Authors: Ondrusova Beata , Tino Peter , Svehlikova Jana
Published: September 2023

Introduction: The inverse problem of electrocardiography noninvasively localizes the origin of undesired cardiac activity, such as a premature ventricular contraction (PVC), from potential recordings from multiple torso electrodes. However, the optimal number and placement of electrodes for an accurate solution of the inverse problem remain undetermined. This study presents a two-step inverse solution for a single dipole cardiac source, which investigates the significance of the torso electrodes on a patient-specific level. Furthermore, the impact of the significant electrodes on the accuracy of the inverse solution is studied.

Methods: Body surface potential recordings from 128 electrodes of 13 patients with PVCs and their corresponding homogeneous and inhomogeneous torso models were used. The inverse problem using a single dipole was solved in two steps: First, using information from all electrodes, and second, using a subset of electrodes sorted in descending order according to their significance estimated by a greedy algorithm. The significance of electrodes was computed for three criteria derived from the singular values of the transfer matrix that correspond to the inversely estimated origin of the PVC computed in the first step. The localization error (LE) was computed as the Euclidean distance between the ground truth and the inversely estimated origin of the PVC. The LE obtained using the 32 and 64 most significant electrodes was compared to the LE obtained when all 128 electrodes were used for the inverse solution.

Results: The average LE calculated for both torso models and using all 128 electrodes was 28.8 ± 11.9 mm. For the three tested criteria, the average LEs were 32.6 ± 19.9 mm, 29.6 ± 14.7 mm, and 28.8 ± 14.5 mm when 32 electrodes were used. When 64 electrodes were used, the average LEs were 30.1 ± 16.8 mm, 29.4 ± 12.0 mm, and 29.5 ± 12.6 mm.

Conclusion: The study found inter-patient variability in the significance of torso electrodes and demonstrated that an accurate localization by the inverse solution with a single dipole could be achieved using a carefully selected reduced number of electrodes.
Implicit learning and individual differences in speech recognition: an exploratory study
Authors: Khayr Ranin , Karawani Hanin , Banai Karen
Published: September 2023

Individual differences in speech recognition in challenging listening environments are pronounced. Studies suggest that implicit learning is one variable that may contribute to this variability. Here, we explored the unique contributions of three indices of implicit learning to individual differences in the recognition of challenging speech. To this end, we assessed three indices of implicit learning (perceptual, statistical, and incidental), three types of challenging speech (natural fast, vocoded, and speech in noise), and cognitive factors associated with speech recognition (vocabulary, working memory, and attention) in a group of 51 young adults. Speech recognition was modeled as a function of the cognitive factors and learning, and the unique contribution of each index of learning was statistically isolated. The three indices of learning were uncorrelated. Whereas all indices of learning had unique contributions to the recognition of natural-fast speech, only statistical learning had a unique contribution to the recognition of speech in noise and vocoded speech. These data suggest that although implicit learning may contribute to the recognition of challenging speech, the contribution may depend on the type of speech challenge and on the learning task.