bluuebunny/crossref_metadata_2025 huggingface dataset:
Does the Use of Angiotensin-Converting Enzyme Inhibitors or Angiotensin II Receptor Blockers Improve Survival in Bladder Cancer?
Authors: Clark Roderick , Wong Kevin , Fan Stacy , Chin Joseph , Izawa Jonathan , Power Nicholas
Published: April 2023

Introduction: The use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB) has been associated with improved bladder cancer outcomes. The objective of this study was to perform a systematic review of the literature and investigate the effects of these medications on survival from our own retrospective database.

Methods: A systematic literature search of PubMed and the Cochrane database was conducted and 34 relevant articles identified. No randomised control trials were identified. After exclusion, five observational studies were included in our analysis. Since there was a paucity of data, we then performed a retrospective cohort study using clinical data from our electronic medical record. All patients who underwent radical cystectomy, with or without adjuvant chemotherapy, at a single tertiary care centre in Ontario, Canada between 2001 and 2016 were identified.

Results: Our literature review found that ACEI or ARB use in upper urinary tract and lower urinary tract non-muscle invasive bladder cancer was associated with increased 5-year recurrence-free, cancer-specific, and overall survival. Our own analysis identified 464 patients who underwent radical cystectomy for muscle-invasive bladder cancer during the study period. Ninety-nine individuals received ACEI or ARB treatment during this time. Cox-proportion hazards modelling suggested that the use of ACEI or ARB was not significantly associated with a survival benefit.

Conclusions: We are unable to support or oppose the use of ACEI or ARB as adjuvant treatment in bladder cancer due to the heterogeneity and quality of published data. Our own study data do not support the use of these medications as adjuvant therapy for muscle-invasive bladder cancer. A randomised control trial in this area of research is required.
Aetiology and Evaluation of Men with Urethral Stricture and the Current Role of Urethroplasty in the Treatment of Anterior Urethral Strictures
Authors: Irekpita Eshiobo , Aigbe Eghosa , Aigbonoga Quincy , Esezobor Emmanuel
Published: April 2023

The estimated prevalence of urethral stricture disease is 229–627 per 100,000 males, though there are regional variations. Trauma, either from external force or iatrogenic causes, is currently the most common single cause of urethral stricture, although, as with prevalence, there are geographical variations. The presentation usually occurs with lower urinary tract symptoms, sometimes with urinary retention and, rarely, with watering can perineum. The symptoms are best evaluated with a combination of the American Urological Association (AUA) Symptom Index and urinary flow rate measurements for both new cases and suspected recurrences.

Time-tested retrograde urethrography remains the gold standard for a confirmatory diagnosis; however, it is limited by its inability to evaluate the posterior urethra and associated morbidities, such as abscesses and fistulas, thus three-dimensional imaging techniques are emerging as adjunct investigations. These modalities are not currently used universally, but their unavailability is not expected to be a serious hindrance to decision-making by a versatile reconstructive urologist.

Urethroplasty is regarded as the gold standard treatment for urethral stricture; excision and primary anastomosis, buccal mucosa graft, skin graft, and pedicle flap techniques have all been used. Notably, buccal mucosal graft urethroplasty has gained popularity above the others because of its versatility and success rate; this is considered to equate to urethral tissue engineering, which is at present confined to only a few centres.
The Shortest Way Home? A Geo-critical Return to C.S. Lewis's Prince Caspian
Authors: Jones Sharon
Published: April 2023

This paper revisits C.S. Lewis's relationship with his Irish roots and offers a geo-critical reading of his 1951 novel Prince Caspian. An excavation of Irish elements latent in this text yields important insights into Lewis's preoccupations, including colonialism and conflict, and ecological crisis. The paper situates these concerns in an Irish cultural context but concludes that Lewis's thinking is of contemporary relevance and worthy of renewed focus, not only in Ireland but globally.
A Note on Owen Barfield on Abortion and the Founding of the SPUC
Authors: Loftin Landon
Published: April 2023

This note brings together what is known about Owen Barfield's role in the founding of the Society for the Protection of Unborn Children and what can be gleaned from Barfield's writings about his views on the matter of abortion.
Case report: A novel surgical technique for rapid valve-in-ring implantation into the native aortic annulus during left ventricular assist device implantation
Authors: Pya Yuriy , Mussayev Abdurashid , Novikova Svetlana , Bekbossynova Makhabbat , Alimbayev Serik , Khissamutdinov Nail , Kapyshev Timur , Kuanyshbek Aidyn , Lesbekov Timur
Published: April 2023

The implantation of a left ventricular assist device (LVAD) has become an essential requirement for managing patients with end-stage heart failure. However, aortic valve insufficiency is a contraindication for LVAD implantation in patients with end-stage heart failure, partly because of the decreasing efficiency of mechanical circulatory support and the eventual development of right ventricular failure. Herein, we present the first case of performing transcatheter aortic valve replacement in valve-in-ring along with LVAD implantation for the treatment of a 60-year-old male suffering from refractory heart failure due to dilated cardiomyopathy and pure aortic insufficiency in need of a new aortic bioprosthesis. A balloon-expandable bioprosthetic transcatheter heart valve was implanted into a previously sewn annulus ring into the aortic root via transaortic access. Subsequently, a centrifugal-flow LVAD was implanted. Postoperatively, the patient was in New York Heart Association Functional Class (NYHA) II with 6-min walk test of 310 m. The patient has completed 6 months of follow-up with no events. This novel and feasible surgical technique reduced the cardiopulmonary bypass time and duration of surgery. Furthermore, it avoids the risk of redo sternotomy and decreases the chances of paravalvular leakage and worsening of aortic regurgitation.
Comparison of different momentum control variables on assimilating radar observations for the forecasts of a dispersive convective event
Authors: Song Wei , Lin Erliang , Qiu Xiaobin , Xue Yuting
Published: April 2023

In this study, the effects of background error covariance (BE) using the stream function ψ and unbalanced velocity potential χu as momentum control variables (CV5 scheme) and BE using the velocity U and V as momentum control variables (CV7 scheme) on assimilating radar radial velocity and reflectivity data for short-term forecasts of dispersive convection in a weak environmental field are explored based on the weather research and forecasting model (WRF) model and its 3DVAR assimilation system. The 4 km resolution forecast samples are generated to formulate the CV5 and CV7 BE by the National Meteorological Center (NMC) method. The single-observation experiments reveal that the differences between the two BE statistics are mainly reflected on the momentum control variables. The increment of wind field from CV7 shows more small-scale local characteristics. Comparing with control experiment, real radar observation assimilation tests of CV5 and CV7 both improve the reflectivity and precipitation forecasts. But the CV7 scheme improves the forecasting of strong convective systems in weak environmental fields better than CV5. First, the CV7 scheme improves both reflectivity and dispersive precipitation forecasts and significantly suppresses the spurious precipitation forecasts when compared with the CV5 scheme. In addition, CV7 also significantly reduces the forecast errors of surface variables and the wind analysis from CV7 is more local. Further analysis shows that the CV7 improves the water vapor convergence conditions compared to the CV5 scheme, which may be the reason for its better performance in the subsequent forecasts.
Flourish-HE: An online positive education programme to promote university student wellbeing
Authors: Morgan Blaire , Simmons Laura , Ayles Nikki
Published: April 2023

Student mental health and wellbeing is both a priority and area of challenge within Higher Education, with providers seeing an increased demand for mental health, counselling and wellbeing support. The current paper argues that an effective preventative approach to supporting university student wellbeing is one that: (a) addresses student wellbeing using a holistic approach; (b) is underpinned by a comprehensive wellbeing theory; (c) aims to promote key dimensions of individual and collective wellbeing; and (d), can align with HE structures and strategies. Consequently, we describe and evaluate a multi-faceted 8-week online wellbeing programme—Flourish-HE—which follows a positive education ethos and is underpinned by the PERMA-H theory of wellbeing. The mixed method evaluation of Flourish-HE employs an explanatory sequential design with matched pre-post quantitative surveys (N = 33) and follow up qualitative interviews (N = 9). The surveys examine pre-post changes in PERMA-H wellbeing facets, mental health outcomes and sense of community with quantitative results indicating significant increases in positive emotion, positive relationships, meaning or purpose in life, overall mental wellbeing and sense of (course) community following participation in the programme, alongside decreases in depressive symptomology. The qualitative findings supported, and provided further explanation for, the pre-post-test differences and highlighted several barriers to engagement in the programme (e.g., unfavourable preconceptions) and future considerations (such as supporting longer-term effects). The evaluation provides evidence to suggest Flourish-HE is an effective wellbeing programme that can be delivered to students in Higher Education.
Optimal energy portfolio method for regulable hydropower plants under the spot market
Authors: Lu Guanpeng , Yang Ping , Li Zhuangzhuang , Yang Yi , Tang Yufeng
Published: April 2023

The energy allocation method for regulable hydropower plants under the spot market significantly impacts their income. The available studies generally draw on the Conditional Value-at-Risk (CVaR) approach, which typically assumes a fixed risk aversion coefficient for generators. This assumption is based on the assumption that the total energy the power plant can allocate is constant during the decision period. However, the amount of energy that the regulable hydropower plant can generate will be affected by inflow and water level during the decision period, and the assumption of the fixed risk aversion coefficient is only partially consistent with the actual decision behavior of the hydropower plant. In this regard, the time-varying relative risk aversion (TVRRA) based method is proposed for the energy allocation of regulable hydropower plants. That method takes the change value of the hydropower plant’s energy generation as the basis for adjusting the time-varying relative risk aversion coefficient to make the energy allocation results more consistent with the actual decision-making needs of the hydropower plant. A two-layer optimal method is proposed to obtain the income-maximizing energy portfolio based on regulable hydropower plants’ time-varying relative risk aversion coefficient. The inner point method solves the optimal energy portfolio of income and risk in the upper layer. The time-varying relative risk aversion coefficient in the lower layer accurately describes the dynamic risk preference of hydropower plants for each period. The results and comparison show that the proposed method increases the income of the energy portfolio by 31%, and water disposal of regulated hydropower plants is reduced by 2%. The energy portfolio optimization method for regulable hydropower plants proposed in this paper not only improves the economic income of hydropower plants but also improves the utilization rate of hydro energy resources and enhances the market competitiveness of regulable hydropower plants.
Assessing disease risk perceptions of wild meat in savanna borderland settlements in Kenya and Tanzania
Authors: Patel Ekta H. , Martin Andimile , Funk Stephan M. , Yongo Moses , Floros Camilla , Thomson Julie , Fa Julia E.
Published: April 2023

Wild meat hunting and trade across African savannas is widespread. We interviewed 299 people in rural settlements along the Kenya-Tanzania border to examine impacts of COVID-19 on wild meat consumption and perceptions about wild meat activities associated with zoonotic disease risks. Education level played a key part in understanding COVID-19 transmission. Information about the pandemic was mostly acquired from the media. Nearly all respondents recognized that COVID-19 originated in China. As many as 70% reported no impact of COVID-19 on wild meat consumption; some believed that there was an increase. Over half of the respondents believed that consumption of wild meat leads to food-borne illnesses. Respondents recognized disease risks such as anthrax and brucellosis and accepted that people slaughtering and handling wild meat with open cuts were at greater risk. Ungulates were the most consumed animals, followed by birds, rodents, and shrews. Respondents perceived that hyenas, monkeys, donkeys, and snakes were riskier to eat. More than 90% of the respondents understood that handwashing with soap reduces risks of disease transmission. Country level (11 answers), education and gender (three answers each) and household economy (158 answers) were significant. Country differences were linked to differences in nature legislation; 50% of Kenyan respondents believed that wild meat should not be sold because of conservation concerns. Men were more worried about getting COVID-19 from live animals and perceived that wildlife should not be sold because of conservation reasons. Overall, there was a very strong inclination to stop buying wild meat if other meats were less expensive. Our results allow us to better understand the impact of the COVID-19 pandemic on wild meat-related activities. Differences between countries can frame the attitudes to wild meat since wild meat trade and consumption were found to be country specific.
Single-cell transcriptome analysis for cancer and biology of the pancreas: A review on recent progress
Authors: Tamaddon Mona , Azimzadeh Mostafa , Gifani Peyman , Tavangar Seyed Mohammad
Published: April 2023

Single-cell sequencing has become one of the most used techniques across the wide field of biology. It has enabled researchers to investigate the whole transcriptome at the cellular level across tissues, which unlocks numerous potentials for basic and applied studies in future diagnosis and therapy. Here, we review the impact of single-cell RNA sequencing, as the prominent single-cell technique, in pancreatic biology and cancer. We discuss the most recent findings about pancreatic physiology and pathophysiology owing to this technological advancement in the past few years. Using single-cell RNA sequencing, researchers have been able to discover cellular heterogeneity across healthy cell types, as well as cancer tissues of the pancreas. We will discuss the new immunological targets and new molecular mechanisms of progression in the microenvironment of pancreatic cancer studied using single-cell RNA sequencing. The scope is not limited to cancer tissues, and we cover novel developmental, evolutionary, physiological, and heterogenic insights that have also been achieved recently for pancreatic tissues. We cover all biological insights derived from the single-cell RNA sequencing data, discuss the corresponding pros and cons, and finally, conclude how future research can move better by utilizing single-cell analysis for pancreatic biology.
Genetic variations in the DYNC2H1 gene causing SRTD3 (short-rib thoracic dysplasia 3 with or without polydactyly)
Authors: Chen Wenqi , Li Yazhou , Zhang Jing , Yuan Yufan , Sun Donglan , Yuan Jiayu , Yang Kai , Liang Ying , Guo Qing
Published: April 2023

Background and aims: Short-rib thoracic dysplasia 3 with or without polydactyly (SRTD3) represents a type of severe fetal skeletal dysplasia (SD) characterized by shortened limbs, narrow thorax with or without polydactyly, which is caused by the homozygous or compound heterozygous mutations in the DYNC2H1 gene. SRTD3 is a recessive disorder, identification of the responsible genetic variation would be beneficial to an accurate prenatal diagnosis and well-grounded counseling for the affected families.

Material and methods: Two families having experienced recurrent fetal SDs were recruited and submitted to a multiplatform genetic investigation. Whole-exome sequencing (WES) was performed with samples collected from the probands. Sanger sequencing and fluorescent quantitative PCR (qPCR) were conducted as validation assays for suspected variations.

Results: WES identified two compound heterozygous variations in the DYNC2H1(NM_001080463.2) gene, namely c.2386C>T (p.Arg796Trp) and c.7289T>C (p.Ile2430Thr) for one; and exon (64–83)del and c.8190G>T (p.Leu2730Phe) for the other, respectively. One variant in them, exon (64–83)del, was novelly identified.

Conclusion: The study detected two compound heterozygous variation in DYNC2H1 including one novel deletion: exon (64–83) del. Our findings clarified the cause of fetal skeletal dysplasia in the subject families, provided guidance for their future pregnancies, and highlighted the value of WES in diagnosis of skeletal dysplasia with unclear prenatal indications.
Multiparametric flow cytometry to characterize vaccine-induced polyfunctional T cell responses and T cell/NK cell exhaustion and memory phenotypes in mouse immuno-oncology models
Authors: Moi Davide , Zeng Bijun , Minnie Simone A. , Bhatt Rituparna , Wood Jack , Sester David P. , Mazzieri Roberta , Dolcetti Riccardo
Published: April 2023

Suitable methods to assess in vivo immunogenicity and therapeutic efficacy of cancer vaccines in preclinical cancer models are critical to overcome current limitations of cancer vaccines and enhance the clinical applicability of this promising immunotherapeutic strategy. In particular, availability of methods allowing the characterization of T cell responses to endogenous tumor antigens is required to assess vaccine potency and improve the antigen formulation. Moreover, multiparametric assays to deeply characterize tumor-induced and therapy-induced immune modulation are relevant to design mechanism-based combination immunotherapies. Here we describe a versatile multiparametric flow cytometry method to assess the polyfunctionality of tumor antigen-specific CD4+ and CD8+ T cell responses based on their production of multiple cytokines after short-term ex vivo restimulation with relevant tumor epitopes of the most common mouse strains. We also report the development and application of two 21-color flow cytometry panels allowing a comprehensive characterization of T cell and natural killer cell exhaustion and memory phenotypes in mice with a particular focus on preclinical cancer models.
From research to health policy: The Noguchi story in the past, present and next 25 years
Authors: Yeboah-Manu Dorothy , Odoom John Kofi , Osei-Wusu Stephen , Adoma-Boakye Afia , Osae-Amoako Griselda , Asante-Poku Adwoa , Akorli Jewelna , Abuaku Benjamin , Kusi Kwadwo Asamoah , Ahorlu Collins Stephen
Published: April 2023

The Noguchi Memorial Institute for Medical Research (NMIMR) is a semi-autonomous institute of the College of Health Sciences, University of Ghana, Legon. Founded in 1979, the Institute was built with a grant aid from the Government of Japan as a gift to the people of Ghana in memory of the renowned Japanese medical scientist, Dr. Hideyo Noguchi, who died from Yellow fever infection while conducting research on the disease in Ghana. The Institute has a three-pronged mandate to conduct health related research, build human capacity and provide specialized diagnostic and disease monitoring services in support of the Ghana Health Service. Over the past 40 years, the Institute has grown to be a leading biomedical research institute in the African region. It has strong and long-standing collaborations with scientists and institutions in Africa, Japan, Europe, Australia and North America on several projects on diseases of public health importance. The Institute also hosts several regional and national centres such as Regional Influenza laboratory. The Institute’s research activities are relevant to the control and prevention of infectious diseases in Ghana, particularly, HIV/AIDS, Tuberculosis, Buruli ulcer, Polio, Malaria and emerging infectious diseases. The Institute also plays a technical/advisory role to government through collaborations with disease control programmes and has since inception provided the country with needed critical evidence in support of health policy as well as laboratory diagnostic services among others. Going forward, the Institute seeks to expand and consolidate its activities in areas of antimicrobial resistance (AMR), clinical trials, genomic surveillance and academic programs and in the next 25 years, NMIMR hopes to approach every research area using the one health approach.
Chromosome-level genome assembly of the yellow boxfish (Ostracion cubicus) provides insights into the evolution of bone plates and ostracitoxin secretion
Authors: Wei Shichao , Zhou Wenliang , Fan Huizhong , Zhang Zhiwei , Guo Weijian , Peng Zhaojie , Wei Fuwen
Published: April 2023

The Ostracion cubicus, commonly known as the yellow boxfish, is a remarkable species with a body encased in a bone plate and the ability to produce an ostracitoxin from their skin when under stress. However, the genetic basis of those effective defense traits is still largely unknown due to the lack of genomic resources. Here, we assembled the first chromosome-level genome of O. cubicus with 867.50 Mb in genome size and 34.86 Mb N50 scaffold length by HiFi and Hi-C sequencing. Twenty-five pseudo-chromosomes, numbered according to size, covered 94.13% of the total assembled sequences. A total of 23,224 protein-coding genes were predicted, with a BUSCO completeness of 98.6%. Positive selection or rapid evolution was observed in genes related to scale and bone development (acsl4a, casr, keap1a, tbx1), and up-regulation of transcription was found in the skin of boxfish (bmp1, bmp2k, bmp4, bmp7, smad5, suco, prelp, mitf), likely associated with the bone plates evolution in the yellow boxfish. An expansion of the solute carrier family 22, a cluster of genes in solute carrier (SLCs) family, transmembrane protein family (TMEMs), vesicle trafficking (SECs), ATP-binding cassette (ABCs) and apolipoproteins (APOs) were identified under positive selection, rapid evolution, or up-regulated in the skin of boxfish, likely associated with the ostracitoxin secretion in the yellow boxfish. Our study not only presents a high-quality boxfish genome but also provides insights into bone plates evolution and ostracitoxin secretion of O. cubicus.
Fabrication of drug-eluting polycaprolactone and chitosan blend microfibers for topical drug delivery applications
Authors: Gizaw Mulugeta , Bani Mustafa Diala , Chou Shih-Feng
Published: April 2023

Chronic and non-healing wounds show delayed and incomplete healing process, which expose the patients to a high risk of infection. These types of wounds require frequent change of dressing, which is a burden on the patients. In addition, ideal dressing needs to meet the requirements in minimizing microbial infiltration and growth while balancing moisture and exchanging oxygen with outside environment. To overcome the challenge in frequent change of dressing and meet the design requirements, current researches have focused on the development of electrospun fibers with incorporation of small molecule drugs for sustained release purpose. In this study, electrospinning was performed to fabricate blend fibers consisting of 15 wt% of polycaprolactone (PCL) and 4 wt% of chitosan (CS) at various blend ratios with the incorporation of a model small molecule drug, acetylsalicylic acid (ASA). Results showed that fibers became more hydrophilic when increasing CS concentration from 0% to 60% in PCL/CS blank fibers. Increasing CS concentration decreased fiber diameter resulting in the decrease of fiber mechanical properties. Furthermore, the addition of 10% w/w ASA also made the fibers more hydrophilic and further decreased the fiber diameter. There were no linear relationships between CS concentrations and fiber mechanical properties in the drug-loaded samples, which indicated some level of drug-polymer interactions. Fiber mechanical properties and drug release rates were two major aspects indicative of strong and/or weak drug-polymer interactions. In vitro drug release in PBS buffer solution showed a burst profile of ASA (30%) up to 2 h followed by a zero-order release rate up to 2 days.
Biofunctionalization of hydrogel-based scaffolds for vascular tissue regeneration
Authors: López-Gutierrez Jorge , Ramos-Payán Rosalío , Ayala-Ham Alfredo , Romero-Quintana José Geovanni , Castillo-Ureta Hipolito , Villegas-Mercado Carlos , Bermúdez Mercedes , Sanchez-Schmitz Guzman , Aguilar-Medina Maribel
Published: April 2023

Congenital and acquired tissular losses due to disease or trauma are a major world health problem. Regenerative therapy aims to fix damaged tissues by directing the natural capacity of a host organism to use biofunctionalized artificial tissue scaffolds. These three-dimensional (3D) scaffolds can be customized with cells and/or bioactive molecules to induce cellular homing and angiogenesis, essential to ensure successful tissue regeneration. Hydrogels (HGs) scaffolds are networks of hydrophilic homopolymers, copolymers, and/or macromers with chemical and biological activities that enhance their cell colonization. The use of HGs in regenerative medicine has shown to be advantageous since HGs can be prepared under clinical-grade conditions and tailored to the specific needs of the replaced tissue. They can be made to emulate native extracellular matrices (ECMs) including physical, mechanical, and chemical cues and resilience properties. These customized HGs can reproduce the natural hygroscopic capacity of the original tissue which improves cellular anchoring, nutrition, and waste disposal. They can enable host molecular and cellular modification conducive to a natural cellular microenvironment, modifying the properties of the scaffold, and improving chemotaxis, cell adhesion, migration, proliferation, differentiation, and angiogenesis; HGs can be created and biofunctionalized with linked growth factors and synthetic peptides tailored to positively influence scaffold colonization and functional biocompatibility. This review aims to collect the most relevant information regarding biofunctionalization of HGs used for vascular tissue regeneration, their biological effects, and their clinical implications. While most biofunctionalized HGs are still under investigation, some of them have been studied in vitro, ex vivo, and in vivo with promising results. In this regard, in vivo studies have shown that biofunctionalized scaffolds with peptides such as chitosan hydrogel with LL-37 promotes angiogenesis and healing of pressure ulcers. Also, the GHK tripeptide is widely used in trials focused on guided tissue remodeling.
Endemic melioidosis in central Taiwan—A longitudinal case cohort study
Authors: Ling Ting Ting , Lee Su-Yin , Tsao Shih-Ming , Liang Keng-Wei , Wang Wei-Yao
Published: April 2023

Background

Melioidosis is a systemic and suppurative disease endemic in the Southeast Asia. In Taiwan, most cases are reported in the southern region and no relevant profiles have been reported in central region. In this study, we performed the epidemiologic and clinical analyses from the melioidosis cases in central Taiwan.

Methods

The demographic, clinical, laboratory, radiologic, and outcome profiles were collected retrospectively and analyzed from patients whom Burkhoderia pseudomallei was isolated from clinical specimens during the 12-year study period (2011–2022).

Results

Totally 11 melioidosis cases (10 males and 1 female) were diagnosed, among them only 2 (18.2%) cases lived in suburban areas. Seven (63.6%) cases were diagnosed during 2019–2020, and diabetes mellitus was the most relevant comorbidity (5, 45.4%). All cases presented with fever at arrival, but only 4 (36.4%) and 2 (18.2%) cases presented with dyspnea and shock, respectively. Pneumonitis and extrapulmonary involvement were found in 5 cases (45.4%) each. Appropriate empiric and targeted antibiotic treatments were found in 4 (36.4%) and 10 (91.0%) case, respectively. Two cases (18.2%) succumbed to infection despite appropriate treatment including targeted antibiotics.

Conclusion

Melioidosis has become endemic in central Taiwan. Septic patients who present with suppurative or undetermined foci and have unsatisfied responses to standard treatment should arouse clinicians to take melioidosis into consideration.
Evaluation of the competence of an artificial intelligence-assisted colonoscopy system in clinical practice: A post hoc analysis
Authors: Zuo Wei , Dai Yongyu , Huang Xiumei , Peng Ren-qun , Li Xinghui , Liu Hao
Published: April 2023

Background

Artificial intelligence-assisted colonoscopy (AIAC) has been proposed and validated in recent years, but the effectiveness of clinic application remains unclear since it was only validated in some clinical trials rather than normal conditions. In addition, previous clinical trials were mostly concerned with colorectal polyp identification, while fewer studies are focusing on adenoma identification and polyps size measurement. In this study, we validated the effectiveness of AIAC in the clinical environment and further investigated its capacity for adenoma identification and polyps size measurement.

Methods

The information of 174 continued patients who went for coloscopy in Chongqing Rongchang District People’s hospital with detected colon polyps was retrospectively collected, and their coloscopy images were divided into three validation datasets, polyps dataset, polyps/adenomas dataset (all containing narrow band image, NBI images), and polyp size measurement dataset (images with biopsy forceps and polyps) to assess the competence of the artificial intelligence system, and compare its diagnostic ability with endoscopists with different experiences.

Results

A total of 174 patients were included, and the sensitivity of the colorectal polyp recognition model was 99.40%, the accuracy of the colorectal adenoma diagnostic model was 93.06%, which was higher than that of endoscopists, and the mean absolute error of the polyp size measurement model was 0.62 mm and the mean relative error was 10.89%, which was lower than that of endoscopists.

Conclusion

Artificial intelligence-assisted model demonstrated higher competence compared with endoscopists and stable diagnosis ability in clinical use.
Chitinase-3 like-protein-1, matrix metalloproteinase -9 and positive intracranial arterial remodelling
Authors: Tang Ming , Zhou Dongyang , He Junhui , Bai Hongying , Li Qianqian , Xu Hui
Published: April 2023

Introduction

Positive intracranial arterial remodelling is a dilated lesion of the large intracranial vessels; however, its pathogenesis is currently unknown. Some studies have identified chitinase-3 like-protein-1 (YKL-40) and matrix metalloproteinase (MMP)-9 as circulating inflammatory factors involved in positive vascular remodelling. Herein, we aimed to investigate the relationship between changes in serum YKL-40 and MMP-9 levels and positive intracranial arterial remodelling in patients with cerebral small vessel disease (CSVD).

Methods

A total of 110 patients with CSVD were selected. Patients with brain arterial remodelling (BAR) scores >1 times the standard deviation were defined as the positive intracranial artery remodelling group (n = 21 cases), and those with BAR scores ≤1 times the standard deviation were defined as the non-positive intracranial artery remodelling group (n = 89 cases). Serum YKL-40 and MMP-9 levels were measured using an enzyme-linked immunosorbent assay kit. Factors influencing positive intracranial artery remodelling using binary logistic regression analysis and predictive value of YKL-40 and MMP-9 for positive intracranial arterial remodelling in patients with CSVD were assessed by a subject receiver operating characteristic curve.

Results

Statistically significant differences in serum YKL-40 and MMP-9 levels were observed between the positive and non-positive remodelling groups (p < 0.05). The integrated indicator (OR = 9.410, 95% CI: 3.156 ~ 28.054, P<0.01) of YKL-40 and MMP-9 levels were independent risk factors for positive intracranial arterial remodelling. The integrated indicator (OR = 3.763, 95% CI: 1.884 ~ 7.517, p < 0.01) of YKL-40 and MMP-9 were independent risk factors for positive arterial remodelling in posterior circulation, but were not significantly associated with positive arterial remodelling in anterior circulation (p > 0.05). The area under the curve for YKL-40 and MMP-9 diagnostic positive remodelling was 0.778 (95% CI: 0.692–0.865, p < 0.01) and 0.736 (95% CI: 0.636–0.837, p < 0.01), respectively.

Discussion

Elevated serum YKL-40 and MMP-9 levels are independent risk factors for positive intracranial arterial remodelling in patients with CSVD and may predict the presence of positive intracranial arterial remodelling, providing new ideas for the mechanism of its occurrence and development and the direction of treatment.
Effect of shape deprivation on retinal thickness in myopic mice using an OCT method
Authors: Duan Ming-Ming , Liu Hui , Zhong Yu-Lin
Published: April 2023

Purpose

The purpose of this study was to study in retina thickness changes in myopic mice using optical coherence tomography (OCT).

Methods

There were 18 mice in the form-deprivation myopia (FDM) group，in which the left eye was not treated as a control;18 untreated mice served as a normal control group. The diopter of all mice was measured 21 days after birth (P21), before form deprivation. After 4 weeks of form deprivation (P49), the refraction, fundus, and retinal sublayer thickness of all mice were measured.

Results

After 4 weeks of form deprivation, the refractive power of the right eye in the FDM group was significantly higher than that in the left eye (p < 0.05). There was no significant change in the refractive power of the left eye in the FDM group compared with the normal control group. The retina, nerve fiber layer (NFL), inner nuclear layer (INL), and outer nuclear layer (ONL) in the right eye of the FDM group were significantly thinner than those of both the FDM and control groups (p < 0.05). There was no significant change in photoreceptor (PR).

Conclusion

Our study highlights that the myopic mice have decreased R thickness, which might reflect the potential pathological mechanism of myopia.
Integrating transcriptomics and metabolomics to analyze the mechanism of hypertension-induced hippocampal injury
Authors: Li Yanan , Chu Xue , Xie Xin , Guo Jinxiu , Meng Junjun , Si Qingying , Jiang Pei
Published: April 2023

Objective

Hypertension is a public health challenge worldwide due to its high prevalence and multiple complications. Hypertension-induced damage to the hippocampus leads to behavioral changes and various brain diseases. Despite the multifaceted effects of hypertension on the hippocampus, the mechanisms underlying hippocampal lesions are still unclear.

Methods

The 32-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were selected as the study subjects. Behavioral experiments such as an open field test (OFT), an elevated plus maze (EPM) test, and the Morris water maze (MWM) test were performed to show the behavioral characteristics of the rats. A comprehensive transcriptomic and metabolomic analysis was performed to understand the changes in the hippocampus at the metabolic and genetic levels.

Results

Behavioral tests showed that, compared to WKY rats, SHR showed not only reduced memory capacity but more hyperactive and impulsive behavior. In addition, transcriptomic analysis screened for 103 differentially expressed genes. Metabolomic analysis screened 56 metabolites with significant differences, including various amino acids and their related metabolites.

Conclusion

Comprehensive analysis showed that hypertension-induced hippocampal lesions are closely associated with differential metabolites and differential genes detected in this study. The results provide a basis for analyzing the mechanisms of hypertension-induced hippocampal damage.
Intermittent hypoxia-induced enhancement of sociability and working memory associates with CNTNAP2 upregulation
Authors: Zhang Qing , Xu Lu , Bai Yang , Chen Peiye , Xing Mengen , Cai Fang , Wu Yili , Song Weihong
Published: April 2023

Introduction

Hypoxia is an environmental risk factor for many disorders throughout life. Perinatal hypoxia contributes to autism spectrum disorder (ASD), while hypoxic conditions in the elderly facilitate memory deficits. However, the effects of hypoxia on adolescence remains elusive. CNTNAP2 is a critical molecule in ASD pathogenesis with undefined mechanisms. We investigate hypoxia’s impact on adolescence and the underlying mechanism related to CNTNAP2.

Methods

Three-chamber social approach test, Y maze, Morris Water Maze and Open Field Test were applied to evaluate behavioral alterations. Immunoblotting, 5′- RACE and dual-luciferase reporter assay were performed to examine CNTNAP2 protein expression, transcription start site (TSS) of human CNTNAP2 gene and CNTNAP2 promoter activity, respectively.

Results

Intermittent hypoxia treatment improved social behaviors and working memory in adolescent mice. CNTNAP2 was increased in the brains of hypoxia-treated mice. The sequencing results identified the TSS at 518 bp upstream of the translation start site ATG. Hypoxia upregulated CNTNAP2 by interacting with functional hypoxia response elements in CNTNAP2 promoter.

Conclusion

Intermittent hypoxia enhanced sociability and working memory associated with CNTNAP2 upregulation. Our study provides novel insights into intermittent hypoxia’s impact on development and the interaction between genetic and environmental risk factors in ASD pathogenesis.
Inhibitory hippocampus-medial septum projection controls locomotion and exploratory behavior
Authors: Chen Yuh-Tarng , Arano Rachel , Guo Jun , Saleem Uzair , Li Ying , Xu Wei
Published: April 2023

Although the hippocampus is generally considered a cognitive center for spatial representation, learning, and memory, increasing evidence supports its roles in regulating locomotion. However, the neuronal mechanisms of the hippocampal regulation of locomotion and exploratory behavior remain unclear. In this study, we found that the inhibitory hippocampal synaptic projection to the medial septum (MS) bi-directionally controls the locomotor speed of mice. The activation of the MS-projecting interneurons in the hippocampus or the activation of the hippocampus-originated inhibitory synaptic terminals in the MS decreased locomotion and exploratory behavior. On the other hand, the inhibition of the hippocampus-originated inhibitory synaptic terminals in the MS increased locomotion. Unlike the septal projecting interneurons, the activation of the hippocampal interneurons projecting to the retrosplenial cortex did not change animal locomotion. Therefore, this study reveals a specific long-range inhibitory synaptic output from the hippocampus to the medial septum in the regulation of animal locomotion.
Oral pyruvate prevents high-intensity interval exercise-induced metabolic acidosis in rats by promoting lactate dehydrogenase reaction
Authors: Che Kaixuan , Yang Yanping , Zhang Jun , Feng Lin , Xie Yan , Li Qinlong , Qiu Junqiang
Published: April 2023

Introduction

There is no denying the clinical benefits of exogenous pyruvate in the treatment of pathological metabolic acidosis. However, whether it can prevent exercise physiological metabolic acidosis, delay the occurrence of exercise fatigue, and improve the beneficial effects of exercise and its internal mechanism remain unclear.

Methods

We randomly divided 24 male SD rats into 3 groups: one group was a control without exercise (CC, n = 8), and the other two groups were supplemented with 616 mg/kg/day pyruvate (EP, n = 8) or distilled water of equal volume (EC, n = 8). These groups completed acute high-intensity interval exercise (HIIE) after 7 days of supplementation. The acid metabolism variables were measured immediately after exercise including blood pH (pHe), base excess (BE), HCO3−, blood lactic acid and skeletal muscle pH (pHi). The redox state was determined by measuring the oxidized coenzyme I/reduced coenzyme I (nicotinamide adenine dinucleotide [NAD+]/reduced NAD+ [NADH]) ratio and lactate/pyruvate (L/P) ratio. In addition, the activities of lactate dehydrogenase A (LDHA), hexokinase (HK), phosphofructokinase (PFK) and pyruvate kinase (PK) were determined by ELISA.

Results

Pyruvate supplementation significantly reversed the decrease of pHe, BE, HCO3− and pHi values after HIIE (p < 0.001), while significantly increased the activities of LDHA (p = 0.048), HK (p = 0.006), and PFK (p = 0.047). Compared with the CC, the NAD+/NADH (p = 0.008) ratio and the activities of LDHA (p = 0.002), HK (p < 0.001), PFK (p < 0.001), and PK (p = 0.006) were significantly improved in EP group.

Discussion

This study provides compelling evidence that oral pyruvate attenuates HIIE-induced intracellular and extracellular acidification, possibly due to increased activity of LDHA, which promotes the absorption of H+ in the LDH reaction. The beneficial effects of improving the redox state and glycolysis rate were also shown. Our results suggest that pyruvate can be used as an oral nutritional supplement to buffer HIIE induced metabolic acidosis.
Investigate the application of postoperative ctDNA-based molecular residual disease detection in monitoring tumor recurrence in patients with non-small cell lung cancer——A retrospective study of ctDNA
Authors: Zhang Xuefei , Zhang Youguo , Zhang Shanli , Wang Sha , Yang Peng , Liu Changhong
Published: April 2023

Purpose

To evaluate whether postoperative circulating tumor DNA (ctDNA) in plasma of patients with non-small cell lung cancer (NSCLC) can be used as a biomarker for early detection of molecular residual disease (MRD) and prediction of postoperative recurrence.

Methods

This study subjects were evaluated patients with surgical resected non-small cell lung cancer. All eligible patients underwent radical surgery operation followed by adjuvant therapy. Tumor tissue samples collected during operation were used to detect tumor mutation genes, and blood samples collected from peripheral veins after operation were used to collect ctDNA. Molecular residue disease (MRD) positive was defined as at least 1 true shared mutation identified in both the tumor sample and a plasma sample from the same patient was.

Results

Positive postoperatively ctDNA was associated with lower recurrence-free survival (RFS).The presence of MRD was a strong predictor of disease recurrence. The relative contribution of ctDNA-based MRD to the prediction of RFS is higher than all other clinicopathological variables, even higher than traditional TNM staging. In addition, MRD-positive patients who received adjuvant therapy had improved RFS compared to those who did not, the RFS of MRD-negative patients receiving adjuvant therapy was lower than that of patients not receiving adjuvant therapy.

Conclusions

Post-operative ctDNA analysis is an effective method for recurrence risk stratification of NSCLC, which is beneficial to the management of patients with NSCLC.
Effectiveness and safety of capecitabine, irinotecan and panitumumab in advanced colorectal cancer
Authors: Yip Pui Lam , Fung Wai Him Brian , Lee Francis Ann Shing , Lee Chak Fei , Wong Natalie Sean Man , Lee Shing Fung
Published: April 2023

Introduction

Capecitabine, irinotecan, and panitumumab (CAPIRI-P) is a controversial regimen for metastatic colorectal cancer, with concerns regarding the efficacy and toxicity. However, its toxicity profile has been improved with dose reduction, and concerns regarding efficacy have been extrapolated from other trials. This retrospective study reports the real-world effectiveness and safety of modified CAPIRI-P (mCAPIRI-P).

Material and methods

Advanced colorectal cancer patients receiving mCAPIPI-P in the first-line setting between July 2019 and December 2021 were analyzed. The progression-free survival on treatment (PFSOT) and overall survival (OS) were estimated using the Kaplan–Meier method, and the association with clinical and disease factors was analyzed using the Cox regression model. Serial changes in carcinoembryonic antigen (CEA) level and treatment toxicity were also evaluated.

Results

A total of 106 patients were included, of whom 97 (92%) and 31 (29%) had left-sided primary and unresectable liver-only disease, respectively. The median PFSOT and OS were 15.4 (95% CI 12.5–18.3) and 25.5 (95% CI 17.6–33.4) months, respectively. Sixteen (51.6%) and 10 (32.3%) liver-only disease patients underwent secondary liver treatment and R0 resection, respectively. In multivariable Cox regression, CEA responders (PFSOT: HR 0.53) and CEA normalization (PFSOT: HR 0.27; OS: HR 0.28) were independent favorable prognostic factors for PFSOT and OS. Grade ≥3 toxicity rate was 43%, mainly related to uncomplicated hematological toxicities.

Conclusion

The real-world data show that mCAPIRI-P is safe and effective as the first-line treatment regimen for RAS wild-type advanced colorectal cancer and warrants further study.