bluuebunny/crossref_metadata_2025 huggingface dataset:
Ecological and environmental predictors of juvenile coral density across the central and western Pacific
Authors: Couch Courtney S. , Oliver Thomas A. , Dettloff Kyle , Huntington Brittany , Tanaka Kisei R. , Vargas-Ángel Bernardo
Published: September 2023

The persistence of Pacific coral reefs is threatened by large-scale mortality resulting from heat stress, storms, overfishing, disease, and land-based pollution. While reefs have demonstrated the ability to recover from these disturbances, recovery potential is highly variable; in part driven by the high spatial variability in the abundance of coral juveniles. However, our understanding of the patterns and predictors of juvenile coral density is hampered by the limited geographic scope of previous studies. Our objectives in this study were to: (1) explore the spatial and temporal patterns of juvenile (1- < 5cm in diameter) colony density across the U.S.-affiliated Pacific islands and atolls; and (2) identify the potential role of ecological and environmental factors which may influence coral juvenile abundance. Juvenile density was quantified as part of NOAA’s National Coral Reef Monitoring Program between 2013 and 2019 using a stratified sampling design across 1,405 forereef sites on 34 islands and atolls. Regional mean juvenile density varied from 1.4 to 10.5 colonies m-2 with the highest densities observed in the northern Mariana Islands, Northwestern Hawaiian Islands, and southern Mariana Islands. Juvenile density significantly increased between sampling periods in the Main Hawaiian Islands, Line Islands and northern Mariana Islands. Survey-weighted generalized linear modeling demonstrated that juvenile density was best predicted by the interaction between time since a heat stress event and heat stress severity, depth, site and sector-level percent coral cover, human density, percent unconsolidated substrate, macroalgal cover, herbivore biomass, and the interaction of sector coral cover area and heat stress, and the interaction of wave power (combination of wave height and period) and heat stress. With the unique scale and gradients across the U.S. Pacific, our study found that the high latitude regions have enhanced juvenile density compared to their lower latitude counterparts. Our results also suggest density is most dependent on the timing and severity of heat stress, depth, stock-recruitment with an open adult population, availability of suitable habitat at the site-scale, and the number of humans in the system.
Palliative care at any stage of amyotrophic lateral sclerosis: a prospective feasibility study
Authors: Zwicker Jocelyn , Smith Ian C. , Rice Jill , Murphy Rebekah , Breiner Ari , McNeely Susan , Duff Maria , Buenger Usha , Zehrt Belinda , Nogo Danica , Watt Christine L.
Published: September 2023

Introduction

Many patients with amyotrophic lateral sclerosis (ALS) receive palliative care (PC) very late or not at all. The impact of PC on patients with ALS and caregivers has not been quantified. Study goals included (1) measuring the impact of early PC on quality of life and mood of patients/caregivers and (2) describing patient/caregiver satisfaction with PC.

Methods

The study was a non-randomized, prospective feasibility study of patients with ALS being treated at The Ottawa Hospital ALS Clinic and their caregivers. Exclusion criteria were age < 18 years, inability to complete questionnaires, and prior receipt of PC. The ALS Specific Quality of Life-Revised (ALSSQOL-R) questionnaire (patients only) and Hospital Anxiety and Depression Scale (HADS) were completed at regular intervals for up to 2 years. Patients accepting a PC consultation completed a post-PC satisfaction survey. Primary outcome measures included ALSSQOL-R and HADS scores compared before and after PC consultation, and between groups receiving and not receiving a PC consultation. Secondary outcome measures included responses on the post-PC satisfaction survey (1 = strongly disagree, 5 = strongly agree).

Results

39 patients with ALS (age 66 ± 10 years, median time from diagnosis = 6 months) and 22 caregivers were enrolled. 32 patients had a PC consultation (30 were virtual). Patients and caregivers agreed with statements that the PC consult was helpful (mean ± SD = 4.54 ± 0.60, range = 3–5) and they would recommend PC to others with ALS (4.59 ± 0.59, range = 3–5). Participants disagreed with statements that the consult would have been better later in disease course (1.87 ± 0.80, range = 1–4) and that it took too much time/energy (1.44 ± 0.85, range = 1–4). Average ALSSQOL-R scores worsened significantly over time. HADS and ALSSQOL-R scores did not significantly differ between groups receiving and not receiving PC.

Conclusion

Patients with ALS and their caregivers found virtual PC consultations beneficial irrespective of disease duration or severity. Offering routine PC to all patients with ALS is feasible and should be considered as part of standard care.

Clinical trial registration

https://clinicaltrials.gov/ct2/show/NCT04257760, identifier NCT04257760.
Quantum molecular resonance electrotherapy (Rexon-Eye) for recalcitrant dry eye in an Asian population
Authors: Foo Valencia Hui Xian , Liu Yu-Chi , Tho Bryan , Tong Louis
Published: September 2023

Objectives

To assess the safety, efficacy, patients’ satisfaction and acceptability of Rexon-Eye electrotherapy in treating Asian severe dry eye disease (DED) patients.

Methods

Prospective parallel-arm pilot study recruiting 40 DED Chinese patients with >moderate recalcitrant DED (Contact Lens Research Unit [CCLRU] > grade 2). Subjects were randomized into 2 groups, undergoing four weekly treatment sessions each: group 1 received full treatment power; group 2 received control treatment (power 1 treatment). Non-invasive tear break-up time (NIBUT), cornea fluorescein staining graded via CCLRU and Schirmer’s I test were compared pre- and 2 months post-treatment. The SPEED and QUEST questionnaires that evaluated subjective symptoms and treatment satisfaction, respectively, at baseline and 2 weeks post-treatment were carried out. Tear cytokine levels in both groups were examined at 2 weeks post-treatment.

Results

The amount of improvement in post-treatment corneal staining in the inferior corneal zone was significant in Group 1 (p = 0.038) but not in Group 2 (p = 0.832). Group 1 eyes with worse baseline staining (total score >9.8) had a significantly greater reduction of corneal staining than those with better baseline staining (−11.7 ± 1.98 vs. −4.6 ± 2.89, p < 0.001). There were no other significant differences in NIBUT, Schirmer’s 1 and cornea fluorescein staining grading within or between the groups.: Group 1 (n = 24) had improved subjective dryness scores compared to Group 2 (n = 16) (SPEED score: 6.38 + 4.16 vs. 10.0 + 6.36, p = 0.04). No significant differences were seen in 11 tear cytokine levels at 2 weeks post-treatment between the 2 groups.

Conclusion

In Asian DED patients treated with Rexon-Eye, inferior cornea staining showed significant improvement compared to placebo, and eyes with greater cornea staining at baseline achieved a greater improvement in staining. There were no other significant improvements in NIBUT and Schirmer’s 1. Rexon-Eye also improved subjective DED scores in 41.7% of eyes without any adverse effects.
Improving brain tumor segmentation with anatomical prior-informed pre-training
Authors: Wang Kang , Li Zeyang , Wang Haoran , Liu Siyu , Pan Mingyuan , Wang Manning , Wang Shuo , Song Zhijian
Published: September 2023

Introduction

Precise delineation of glioblastoma in multi-parameter magnetic resonance images is pivotal for neurosurgery and subsequent treatment monitoring. Transformer models have shown promise in brain tumor segmentation, but their efficacy heavily depends on a substantial amount of annotated data. To address the scarcity of annotated data and improve model robustness, self-supervised learning methods using masked autoencoders have been devised. Nevertheless, these methods have not incorporated the anatomical priors of brain structures.

Methods

This study proposed an anatomical prior-informed masking strategy to enhance the pre-training of masked autoencoders, which combines data-driven reconstruction with anatomical knowledge. We investigate the likelihood of tumor presence in various brain structures, and this information is then utilized to guide the masking procedure.

Results

Compared with random masking, our method enables the pre-training to concentrate on regions that are more pertinent to downstream segmentation. Experiments conducted on the BraTS21 dataset demonstrate that our proposed method surpasses the performance of state-of-the-art self-supervised learning techniques. It enhances brain tumor segmentation in terms of both accuracy and data efficiency.

Discussion

Tailored mechanisms designed to extract valuable information from extensive data could enhance computational efficiency and performance, resulting in increased precision. It's still promising to integrate anatomical priors and vision approaches.
Treatment of metastatic squamous cell carcinoma arising in sacrococcygeal pilonidal sinus: a case report series
Authors: Soria Rivas Ainara , Bea-Ardebol Sonia , Vida Navas Elena , Muñoz-Arrones Óscar M. , Cabañas-Montero Luis Jacobo , Mena-Mateos Antonio , López-Campos Fernando , Corral Moreno Sara , Pérez-Muñoz Israel , González Lizan Fausto , Sanz Pascual María , Serrano Domingo Juan Jose
Published: September 2023

Background

Squamous cell carcinoma (SCC) arising in a sacrococcygeal pilonidal sinus is rare, with cases of metastatic disease being even rarer. Among published cases, almost none have reported on systemic treatment.

Objective

This disease has a poorer prognosis than other forms of cutaneous SCC; therefore, our objective is to shed some light on the treatment of metastatic disease.

Methods

We present a series of nine cases treated at a single center, four of whom received systemic treatment. Additionally, other previously reported cases of metastatic disease are included in an attempt to draw stronger conclusions.

Results

Four patients were treated under several treatment regimens, with a median progression-free survival of only 2 months and two instances of partial response (18%). The best result was achieved with cemiplimab. Across all the cases, there was a trend toward a benefit of the use of systemic treatment (HR 0.41, 95% CI 0.15–1.12, p = 0.083; median overall survival 13 vs. 8 months).

Limitations

Limitations include the significant lack of information on previously published cases and the extremely heterogeneous nature of the existing information.

Conclusion

The initial systemic treatment should be an anti-PD-1, as with other SCCs. After progression on anti-PD-1, there is no strong evidence to support the recommendation of a specific treatment or sequence: options include cetuximab and/or chemotherapy (platinum, paclitaxel, 5-fluorouracyl).
Clinical characteristics and outcomes of acute kidney injury in patients with severe fever with thrombocytopenia syndrome
Authors: Zhang Zhongwei , Hu Xue , Jiang Qunqun , Hu Wenjia , Li Anling , Deng Liping , Xiong Yong
Published: September 2023

Background

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonosis caused by a novel bunyavirus. Until recently, the SFTS related acute kidney injury (AKI) was largely unexplored. This study aimed to investigate the clinical characteristics and outcomes of AKI in patients with SFTS.

Methods

The non-AKI and AKI groups were compared in terms of general characteristics, clinical features, laboratory parameters and cumulative survival rate. The independent risk factors for in-hospital mortality in patients with SFTS were analyzed by multivariate logistic regression to identify the population with poor prognosis.

Results

A total of 208 consecutive patients diagnosed with SFTS were enrolled, including 153 (73.6%) patients in the non-AKI group and 55 (26.4%) patients in the AKI group. Compared with patients without AKI, patients with AKI were older and had a higher frequency of diabetes. Among these laboratory parameters, platelet count, albumin and fibrinogen levels of patients with AKI were identified to be significantly lower than those of patients without AKI, while ALT, AST, ALP, triglyceride, LDH, BUN, uric acid, creatine, Cys-C, β2-MG, potassium, AMY, lipase, CK-MB, TnI, BNP, APTT, thrombin time, D-dimer, CRP, IL-6, PCT and ESR levels were significantly higher in patients with AKI. A higher SFTS viral load was also detected in the AKI patients than in the non-AKI patients. The cumulative survival rates of patients at AKI stage 2 or 3 were significantly lower than those of patients without AKI or at AKI stage 1. However, there was no significant difference in the cumulative survival rates between patients without AKI and those with stage 1 AKI. Univariate and multivariate binary logistic regression analyses demonstrated that stage 2 or 3 AKI was an independent risk factor for in-hospital mortality in patients with SFTS.

Conclusion

AKI is associated with poor outcomes in patients with SFTS, especially patients at AKI stage 2 or 3, who generally have high mortality. Our findings support the importance of early identification and timely treatment of AKI in patients with SFTS.
A retrospective study of myelin oligodendrocyte glycoprotein antibody-associated disease from a clinical laboratory perspective
Authors: Wang Yufei , Danzeng Qusang , Jiang Wencan , Han Bingqing , Zhu Xiaowen , Liu Ziwei , Sun Jialu , Chen Kelin , Zhang Guojun
Published: September 2023

Objectives

To analyze the differences in laboratory data between patients with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD).

Methods

The study included 26 MOGAD patients who visited Beijing Tiantan Hospital from 2018 to 2021. MS and NMOSD patients who visited the clinic during the same period were selected as controls. Relevant indicators were compared between the MOGAD group and the MS/NMOSD groups, and the diagnostic performance of meaningful markers was assessed.

Results

The MOGAD group showed a slight female preponderance of 57.7%, with an average onset age of 29.8 years. The absolute and relative counts of neutrophils were higher in the MOGAD group than in the MS group, while the proportion of lymphocytes was lower. The cerebrospinal fluid (CSF) IgG level, IgG index, 24-h IgG synthesis rate, and positive rate of oligoclonal bands (OCB) were lower in MOGAD patients than in the MS group. The area under ROC curve (AUC) was 0.939 when combining the relative lymphocyte count and IgG index. Compared to the NMOSD group, the MOGAD group had higher levels of serum complement C4 and lower levels of serum IgG. The AUC of serum C4 combined with FT4 was 0.783.

Conclusion

Statistically significant markers were observed in the laboratory data of MOGAD patients compared to MS/NMOSD patients. The relative lymphocyte count combined with IgG index had excellent diagnostic efficacy for MOGAD and MS, while serum C4 combined with FT4 had better diagnostic efficacy for MOGAD and NMOSD.
Effect of changes in the hearing aid subsidy on the prevalence of hearing loss in South Korea
Authors: Yoon Chul Young , Lee Junhun , Kong Tae Hoon , Seo Young Joon
Published: September 2023

Objectives

South Korea's National Health Insurance has provided hearing aids to registered individuals with hearing disabilities since 1989. In 2015, hearing aid subsidies increased to approximately US$1,000. This study aimed to understand hearing loss categories in Korea by analyzing patients between 2010 and 2020 and the effect of the 2015 hearing aid policy change on the prevalence of hearing loss.

Methods

The participants were patients registered on the National Health Insurance Service database from 2010 to 2020 with hearing loss. A total of 5,784,429 patients were included in this study. Hearing loss was classified into conductive, sensorineural, and other categories. Patients with hearing loss were classified according to the International Classification of Diseases diagnostic code. Disability diagnosis and hearing aid prescription were defined using the National Health Insurance Disability and Hearing Aid Code.

Results

The increase in hearing aid prescriptions and hearing disability registrations following the subsidy increase impacts hearing loss prevalence. Hearing aid prescription and hearing disability were found to have an effect on increasing hearing loss prevalence in univariate and multivariate analyses. The r-value of each analysis exceeded 0.95. Other hearing losses increased rapidly after the increased subsidy.

Conclusion

A hearing-impaired individual must be diagnosed with a hearing disability and prescribed a hearing aid to receive the subsidy. The prevalence of hearing loss was affected by increased hearing disabilities following changes in the hearing aid subsidy and the number of people prescribed hearing aids. Therefore, caution should be exercised when studying hearing loss prevalence over mid-long-term periods.
Factors that impact dysphagia and discontinuance of oral intake in patients with progressive supranuclear palsy
Authors: Iwashita Yuki , Umemoto George , Fujioka Shinsuke , Arahata Hajime , Dotsu Yuriko , Oike Asami , Tsuboi Yoshio
Published: September 2023

Objective

To evaluate the swallowing function in the advanced stages of progressive supranuclear palsy (PSP) and clarify the factors that lead to adjustment of food consistency and discontinuation of oral intake.

Methods

A total of 56 patients with PSP were recruited. Based on medical records, information about the basic attributes, clinical features (including axial rigidity and dementia), food intake, the results of a videofluoroscopic swallowing study (VFSS), and the timing of nasogastric tube transition and gastrostomy were extracted. From the VFSS images, the presence or absence of aspiration and retrocollis were assessed.

Results

The average age at the onset, diagnosis, and the final follow-up examination were 67.6 ± 6.4 years, 71.6 ± 5.8 years, and 75.4 ± 5.6 years, respectively. The average duration of illness was 64.6 ± 42.8 months. Twenty-four individuals (42.9%) were continuing oral intake, while 32 were tube-fed, among whom 16 (50.0%) underwent gastrostomy tube placement. There were significant differences in the duration from the disease onset to tube feeding between the patients with and without cognitive decline at the time of the diagnosis (p < 0.01) and in the duration from the initial VFSS to tube feeding between the patients with and without aspiration on the initial VFSS (p < 0.01). There were significant differences in the duration from the diagnosis to tube feeding and from the initial VFSS to tube feeding between patients with and without axial rigidity at the time of the diagnosis (p < 0.05 and p < 0.05, respectively). Additionally, there was a significant association between axial rigidity and retrocollis (p < 0.01).

Conclusion

Cognitive decline, axial rigidity and retrocollis, which are associated with the deterioration of dysphagia in PSP, are the highest risk factors for the discontinuation of oral intake. The early identification of these factors associated with the progression of dysphagia can contribute to the improvement of patient care and management.
Conceptualizing healthy cognitive aging: the role of time and variability
Authors: Rodrigues Emma A. , Moreno Sylvain
Published: September 2023

The interest in healthy cognitive aging (HCA) has increased substantially over the past decade. Researchers are interested in exploring how health can be promoted and cognitive decline mitigated when pathology is not present. Identifying the necessary strategies is crucial as the gradual accumulation of small declines can lead to negative effects on quality of life over time. However, the conceptualization of HCA is not agreed upon. In fact, authors often turn to the use of traditional pathology screeners in the context of HCA because of their clear threshold results and their wide use in the different fields. This leads to the assumption that individuals are either cognitively unhealthy and therefore may have some form of dementia or are dementia-free and cognitively healthy. We believe that this view is an overly simplistic approach to the understanding of the aging process. In this work, we explore how HCA has been defined and conceptualized within the different fields. We further discuss how time and variability are key concepts that are often missing when studying HCA and propose a definition that aims to unify the findings from the multidisciplinary research that studies HCA and simplify the translation of knowledge. Incorporating these two novel dimensions to the study of HCA has already been proposed methodologically but has yet been discussed at the conceptual level. We believe that the proposed new approach will allow the identification of individual factors that cause changes in cognitive health and will help build new cognitive health strategies and mitigate further declines.
Considering tradeoffs in “local” food policies: examples from school feeding programmes
Authors: Jablonski Becca B. R. , Milbourne Paul , Maderson Siobhan , Morgan Kevin
Published: September 2023

City, national, and multinational governments are increasingly leveraging nutrition programme spending, specifically pursuing policies that require or incentive “local” procurement, to meet a myriad of goals. However, these policies involve tradeoffs that are often not fully considered by government officials, planners, and advocates. This perspective article provides some examples of those tradeoffs from the peer-reviewed literature, which, we argue, are useful to consider in setting school feeding programme policies to achieve sustainability goals.
Local anaesthesia vs. general anaesthesia for percutaneous microwave ablation in hepatocellular carcinoma: efficacy, safety, and cost analysis
Authors: Zhan Jing-Ying , Zhao Dan , Tang Zhen-Lei , Leng Hao-Qun
Published: September 2023

Purpose

To compare the efficacy, safety, and cost of local anaesthesia and general anaesthesia modalities for percutaneous microwave ablation as a curative treatment for hepatocellular carcinoma patients.

Methods

This comparative, retrospective study analysed 175 patients who were treated for hepatocellular carcinoma (HCC) from July 2015 to September 2020. Conventional transcatheter arterial chemoembolization (cTACE) combined with sequential percutaneous microwave ablation (MWA) was performed on every lesion in every patient. Patients were divided into two cohorts according to the anaesthesia modality applied during MWA. To investigate the differences in efficacy between the two groups, overall survival (OS) and local recurrence-free survival (LRFS) were estimated by the Kaplan−Meier method and compared by the log-rank test. Cost and safety between the two groups were also compared accordingly.

Results

There were 105 patients with 128 HCC lesions in the local anaesthesia (LA) group and 70 patients with 107 lesions in the general anaesthesia (GA) group. There were no significant differences in OS (P = 0.798) or LRFS (P = 0.406) between the two groups. Fifty-two pairs of patients were matched with 77 lesions in the GA group and 67 lesions in the LA group after PSM. There was no significant difference in OS (P = 0.522) or LRFS (P = 0.410) between the two groups. Compared to the LA group, the GA group had longer operations, consumed more medical resources, had a heavier financial burden, and experienced more anaesthesia adverse events. There was no significant difference in the incidence of post-ablation pain (p=0.487), fever (P=0.678), nausea or vomiting (P=0.808), mild liver dysfunction (P=0.753), haemolytic uraemic syndrome (P=0.595), pleural effusion (P=0.622), liver abscess (0.544), asymptomatic perihepatic fluid (0.703) or subcapsular liver hemorrhage (P=0.666) between the two groups.

Conclusion

Due to the higher cost and adverse events of general anaesthesia, local anaesthesia may be more suitable for ablation procedures for HCC patients within the Milan criteria.
Cellular senescence: a double-edged sword in cancer therapy
Authors: Xiao Shuai , Qin Dongmin , Hou Xueyang , Tian Lingli , Yu Yeping , Zhang Rui , Lyu Hao , Guo Dong , Chen Xing-Zhen , Zhou Cefan , Tang Jingfeng
Published: September 2023

Over the past few decades, cellular senescence has been identified in cancer patients undergoing chemotherapy and radiotherapy. Senescent cells are generally characterized by permanent cell cycle arrest as a response to endogenous and exogenous stresses. In addition to exiting the cell cycle process, cellular senescence also triggers profound phenotypic changes such as senescence-associated secretory phenotype (SASP), autophagy modulation, or metabolic reprograming. Consequently, cellular senescence is often considered as a tumor-suppressive mechanism that permanently arrests cells at risk of malignant transformation. However, accumulating evidence shows that therapy-induced senescence can promote epithelial-mesenchymal transition and tumorigenesis in neighboring cells, as well as re-entry into the cell cycle and activation of cancer stem cells, thereby promoting cancer cell survival. Therefore, it is particularly important to rapidly eliminate therapy-induced senescent cells in patients with cancer. Here we review the hallmarks of cellular senescence and the relationship between cellular senescence and cancer. We also discuss several pathways to induce senescence in tumor therapy, as well as strategies to eliminate senescent cells after cancer treatment. We believe that exploiting the intersection between cellular senescence and tumor cells is an important means to defeat tumors.
System analysis based on the lysosome-related genes identifies HPS4 as a novel therapy target for liver hepatocellular carcinoma
Authors: He Ke‐Jie , Nie Zhiqiang
Published: September 2023

Background

Liver cancer is a leading cause of cancer-related deaths worldwide. Lysosomal dysfunction is implicated in cancer progression; however, prognostic prediction models based on lysosome-related genes (LRGs) are lacking in liver cancer. This study aimed to establish an LRG-based model to improve prognosis prediction and explore potential therapeutic targets in liver cancer.

Methods

Expression profiles of 61 LRGs were analyzed in The Cancer Genome Atlas liver cancer cohorts. There were 14 LRGs identified, and their association with clinical outcomes was evaluated. Unsupervised clustering, Cox regression, and functional assays were performed.

Results

Patients were classified into high-risk and low-risk subgroups based on the 14 LRGs. The high-risk group had significantly worse overall survival. Aberrant immune infiltration and checkpoint expression were observed in the high-risk group. Furthermore, HPS4 was identified as an independent prognostic indicator. Knockdown of HPS4 suppressed liver cancer cell proliferation and induced apoptosis.

Conclusion

This study developed an LRG-based prognostic model to improve risk stratification in liver cancer. The potential value of HPS4 as a therapeutic target and biomarker was demonstrated. Regulation of HPS4 may offer novel strategies for precision treatment in liver cancer patients.
Arylsulfatase D is a prognostic biomarker that promotes glioma cells progression through JAK2/STAT3 pathway and M2 macrophage infiltration
Authors: Song Zihan , Zhao Zijun , Zhu Siyu , Jin Qianxu , Zhang Shiyang , Wang Zairan , Shen Bowei , Wang Zijian , Zhao Zongmao
Published: September 2023

Background

Arylsulfatase D (ARSD) belongs to the sulfatase family and plays a crucial role in maintaining the proper structure of bone and cartilage matrix. Although several researches have revealed the functions of ARSD in tumor progression, the prognostic value of ARSD in glioma and the related mechanisms have not been fully investigated.

Methods

We performed a pan-cancer analysis of ARSD, and investigated the relationship between expression of ARSD and overall survival (OS) in multiple glioma datasets. ROC curves and nomograms were created to investigate the predictive capacity of ARSD. Immune and analysis were conducted to investigate the mechanisms underlying the roles of ARSD in glioma. Glioma tissue samples were collected to verify the expression of ARSD in glioma, while the functions of ARSD were explored using cell experiment. M2 macrophage infiltration assay was used to determine the relation between ARSD and tumor immune microenvironment.

Results

Survival analysis indicated that individuals with high ARSD expression in glioma had a shorter survival time. Cox analysis showed that ARSD had a good ability for predicting prognosis in glioma. Immune analysis suggested that ARSD could regulate immune cell infiltration and affect the Cancer-Immunity Cycle to create an immunosuppressive environment. Combined with cell experiment and bioinformatic analysis, we found that ARSD can promote glioma progression through regulation of JAK2/STAT3 pathway and M2 macrophage infiltration.

Conclusion

Our study found that ARSD can promote glioma development by regulating immune microenvironment and JAK2/STAT3 signaling pathway, which provided a potential therapy target for glioma treatment.
Bridging the age gap: a review of molecularly informed treatments for glioma in adolescents and young adults
Authors: Weiser Annette , Sanchez Bergman Astrid , Machaalani Charbel , Bennett Julie , Roth Patrick , Reimann Regina R. , Nazarian Javad , Guerreiro Stucklin Ana S.
Published: September 2023

Gliomas are the most common primary central nervous system (CNS) tumors and a major cause of cancer-related mortality in children (age <15 years), adolescents and young adults (AYA, ages 15–39 years), and adults (age >39 years). Molecular pathology has helped enhance the characterization of these tumors, revealing a heterogeneous and ever more complex group of malignancies. Recent molecular analyses have led to an increased appreciation of common genomic alterations prevalent across all ages. The 2021 World Health Organization (WHO) CNS tumor classification, 5th edition (WHO CNS5) brings forward a nomenclature distinguishing “pediatric-type” and “adult-type” gliomas. The spectrum of gliomas in AYA comprises both “pediatric-like” and “adult-like” tumor entities but remains ill-defined. With fragmentation of clinical management between pediatric and adult centers, AYAs face challenges related to gaps in medical care, lower rates of enrollment in clinical trials and additional psychosocial and economic challenges. This calls for a rethinking of diagnostic and therapeutic approaches, to improve access to appropriate testing and potentially beneficial treatments to patients of all ages.
Enfortumab vedotin in metastatic urothelial carcinoma: the solution EVentually?
Authors: Maiorano Brigida Anna , Catalano Martina , Maiello Evaristo , Roviello Giandomenico
Published: September 2023

Metastatic urothelial carcinoma (mUC) is an aggressive malignancy with a dismal prognosis. Enfortumab vedotin (EV) is an antibody-drug conjugate consisting of an antibody targeting Nectin-4. This protein is highly expressed in UC cells. After binding, monomethyl auristatin E is released into cells, causing UC cell death. EV has been approved as a single agent for pre-treated mUC, with interesting improvements in response rate and survival in a setting with limited treatment options. More recently, EV approval occurred in cisplatin-ineligible naïve mUC patients in combination with pembrolizumab. Our review aims to summarize the pharmacological properties, clinical studies, and future developments of EV in mUC.
Bitter taste receptor (TAS2R) 46 in human skeletal muscle: expression and activity
Authors: Talmon Maria , Massara Erika , Quaregna Martina , De Battisti Marta , Boccafoschi Francesca , Lecchi Giulia , Puppo Federico , Bettega Cajandab Michele A. , Salamone Stefano , Bovio Enrica , Boldorini Renzo , Riva Beatrice , Pollastro Federica , Fresu Luigia G.
Published: September 2023

Bitter taste receptors are involved not only in taste perception but in various physiological functions as their anatomical location is not restricted to the gustatory system. We previously demonstrated expression and activity of the subtype hTAS2R46 in human airway smooth muscle and broncho-epithelial cells, and here we show its expression and functionality in human skeletal muscle cells. Three different cellular models were used: micro-dissected human skeletal tissues, human myoblasts/myotubes and human skeletal muscle cells differentiated from urine stem cells of healthy donors. We used qPCR, immunohistochemistry and immunofluorescence analysis to evaluate gene and protein hTAS2R46 expression. In order to explore receptor activity, cells were incubated with the specific bitter ligands absinthin and 3ß-hydroxydihydrocostunolide, and calcium oscillation and relaxation were evaluated by calcium imaging and collagen assay, respectively, after a cholinergic stimulus. We show, for the first time, experimentally the presence and functionality of a type 2 bitter receptor in human skeletal muscle cells. Given the tendentially protective role of the bitter receptors starting from the oral cavity and following also in the other ectopic sites, and given its expression already at the myoblast level, we hypothesize that the bitter receptor can play an important role in the development, maintenance and in the protection of muscle tissue functions.
Acceptance rate of clinical pharmacists’ recommendations—an ongoing journey for integration
Authors: Peled Orit , Vitzrabin Yael , Beit Ner Eran , Lazaryan Moran , Berlin Maya , Barchel Dana , Berkovitch Matitiahu , Beer Yiftah , Tamir Eran
Published: September 2023

Introduction: Multidisciplinary expert team collaboration in the clinical setting, which includes clinical pharmacist involvement can facilitate significant improvements in outcomes and optimize patient management by preventing drug-related problems (DRP). This type of collaboration is particularly valuable in patients with multi-morbidity and polypharmacy such as diabetic foot patients. Evidence regarding the successful integration of a new clinical pharmacist, without previous experience into a unit is still scarce. Therefore, this study aimed to describe and evaluate the actual successful integration process of the clinical pharmacist into a diabetic foot unit by measuring the change in recommendation acceptance rate over time.

Methods: A prospective, exploratory treatment effectiveness study based on the recommendation acceptance rate of a new clinical pharmacist introduced into the diabetic foot unit was conducted over a 9- month period. The clinical pharmacist identified medical and drug-related problems (DRP) or any discrepancies in the prescribing and administration of medications. Each identified DRP was documented and formulated as a recommendation by the clinical pharmacist. The main outcome measure was the acceptance rate of recommendations over time.

Results: A total of 86 patients, of which 67% were men, averagely aged 66.5 (SD 11.8) years were evaluated. Calculated BMI was 30.2 (SD 6.2). The average number of medical diagnoses was 8.9 (SD3.2), and 11.1 (SD 3.7) prescribed drugs for each patient. Cardiovascular disease was presented by 95% (n = 82) of the patients and 33% of them (n = 28) had uncontrolled hyperglycemia. Averagely, 3.3 (SD 1.9) DRPs were identified pre patient. The efficacy-related DRP recommendation acceptance rate increased over the study period from 37.8% in the first 4 months to 79.4% after a period of 4.75 months. Safety-related DRP recommendation acceptance rate increased from 56% to 67.6%.

Conclusion: Improved clinical outcomes and optimized pharmacologic patient management may be achieved by the successful integration of a clinical pharmacist into the team. This study provides evidence of the increasing recommendation acceptance rate of integrated, pharmacist-driven comprehensive medication management in an unexperienced unit. To overcome challenges, team members should collaborate to fully integrate the clinical pharmacist into the team-based structure and utilize proper strategies to minimize and transcend barriers.
The utility of the reperfusion rate of tissue oxygen saturation as a measure of vascular endothelial function in adolescents: reliability, validity and sensitivity
Authors: Kranen Sascha H. , Oliveira Ricardo S. , Bond Bert , Williams Craig A. , Barker Alan R.
Published: September 2023

Introduction: The near-infrared spectroscopy (NIRS)-derived reperfusion rate of tissue oxygen saturation (slope 2 StO2) may provide a surrogate measure of vascular function, however, this has yet to be examined in a paediatric population. This study investigated in adolescents: 1) the between-day reliability of NIRS-derived measurements; 2) the relationship between slope 2 StO2 and macro- (flow-mediated dilation, FMD) and microvascular (peak reactive hyperaemia, PRH) function; and 3) the effect of high-intensity interval exercise (HIIE) on slope 2 StO2, FMD, and PRH.

Methods: Nineteen boys (13.3 ± 0.5 y) visited the laboratory on two occasions, separated by ∼ 1 week. On visit 1, participants underwent simultaneous assessment of brachial artery FMD and slope 2 StO2 and PRH on the internal face of the forearm. On visit 2, participants completed a bout of HIIE with slope 2 StO2, FMD and PRH measured pre-, immediately post- and 1.5 h post-exercise.

Results: Slope 2 StO2 showed no mean bias (p = 0.18) and an intraclass correlation coefficient of 0.67 (p = 0.003) between visits. No significant correlation between slope 2 StO2 and FMD or PRH was observed on visit 1 (r = −0.04, p = 0.89 and r = −0.30, p = 0.23, respectively) or visit 2 pre-exercise (r = −0.28, p = 0.25 and r = −0.31, p = 0.20, respectively). Compared to pre-exercise, FMD decreased immediately post-exercise (p < 0.001) and then increased 1.5 h post-exercise (p < 0.001). No significant change was detected for slope 2 StO2 (p = 0.30) or PRH (p = 0.55) following HIIE.

Conclusion: In adolescents, slope 2 StO2 can be measured reliably, however, it is not correlated with FMD or PRH and does not follow the acute time course of changes in FMD post-exercise. Hence, the use of slope 2 StO2 as a surrogate measure of vascular function in youth must be refuted.
Interactions between extracorporeal support and the cardiopulmonary system
Authors: Bachmann Kaspar F. , Berger David , Moller Per Werner
Published: September 2023

This review describes the intricate physiological interactions involved in the application of extracorporeal therapy, with specific focus on cardiopulmonary relationships. Extracorporeal therapy significantly influences cardiovascular and pulmonary physiology, highlighting the necessity for clinicians to understand these interactions for improved patient care. Veno-arterial extracorporeal membrane oxygenation (veno-arterial ECMO) unloads the right ventricle and increases left ventricular (LV) afterload, potentially exacerbating LV failure and pulmonary edema. Veno-venous (VV) ECMO presents different challenges, where optimal device and ventilator settings remain unknown. Influences on right heart function and native gas exchange as well as end-expiratory lung volumes are important concepts that should be incorporated into daily practice. Future studies should not be limited to large clinical trials focused on mortality but rather address physiological questions to advance the understanding of extracorporeal therapies. This includes exploring optimal device and ventilator settings in VV ECMO, standardizing cardiopulmonary function monitoring strategies, and developing better strategies for device management throughout their use. In this regard, small human or animal studies and computational physiological modeling may contribute valuable insights into optimizing the management of extracorporeal therapies.
Multiple cryosauna sessions for post-exercise recovery of delayed onset muscle soreness (DOMS): a randomized control trial
Authors: Wolska Beata , Domagała Łukasz , Kisilewicz Aleksandra , Hassanlouei Hamidollah , Makar Piotr , Kawczyński Adam , Klich Sebastian
Published: September 2023

The main goal was to investigate the effectiveness of cryosauna in preventing the development of delayed onset muscle soreness and to analyze the regenerative changes within muscles after acute fatigue-induced exercises. Thirty-one volunteers were assigned into two groups: 1) an intervention group that participated in cryostimulation after fatigue-induced exercise protocol (CRYO, n = 16) and a control group that performed fatigue-induced exercise protocol, but without any intervention (CONT, n = 15). Main outcome measures include at baseline: blood sample testing (leukocyte content, myoglobin concentration, and creatine kinase activity) and muscle stiffness of lower extremity; immediately after (stiffness), and 24-48-72-96 h post-exercise (blood samples and stiffness). Both groups performed an exercise-induced muscle damage protocol based on repeated countermovement jumps (10 sets, 10 repetitions). The CRYO group underwent a cryosauna (temperature: −110°C, time: 1.5 min per session) intervention during four sessions (i.e., immediately after, 24-48-72 h post-exercise). Leukocyte content was significantly greater 24-48-72 h after exercise in CONT, compared with the CRYO group (p ≤ 0.05 for all), while creatine kinase activity was greater 24-48-96 h in CONT, compared with the CRYO group (p ≤ 0.05 for all). Muscle stiffness increased significantly in rectus femoris, tibialis anterior, and fibula muscle after 48 h post-exercise (p ≤ 0.05 for all), as well as in tibialis anterior and fibula after 72 h post-exercise (p ≤ 0.05 for all) in the CRYO group. Multiple cryosauna was an effective recovery strategy that reduced blood biomarkers and muscle stiffness after exercise-induced muscle damage. Moreover, the development of delayed onset muscle soreness, expressed by a greater muscle stiffness post-exercise, was attenuated to the first 48 h.
Alleviation of banded leaf and sheath blight disease incidence in maize by bacterial volatile organic compounds and molecular docking of targeted inhibitors in Rhizoctonia solani
Authors: Yasmin Humaira , Shah Zafar Abbas , Mumtaz Saqib , Ilyas Noshin , Rashid Urooj , Alsahli Abdulaziz Abdullah , Chung Yong Suk
Published: September 2023

Rhizoctonia solani (RS) is a pathogenic fungus that affects maize (Zea mays L.) plants and causes banded leaf and sheath blight (BLSB) with severe consequences leading to significant economic losses. Contrarily, rhizobacteria produce numerous volatile organic compounds (VOCs) that help in devising the environment-friendly mechanism for promoting plant growth and stress alleviation without having physical contact with plants. In the present study, 15 rhizobacterial strains were tested for their antagonism against RS. The antagonistic potential of VOCs of the tested plant growth-promoting rhizobacteria (PGPR) strains ranged from 50% to 80% as compared to the control (without PGPR). Among these 15 strains, the maximum (80%) antagonistic activity was exhibited by Pseudomonas pseudoalcaligenes SRM-16. Thus, the potential of VOCs produced by P. pseudoalcaligenes SRM-16 to alleviate the BLSB disease in maize was evaluated. A pot experiment was conducted under greenhouse conditions to observe the effect of VOCs on disease resistance of BLSB-infected seedlings. Overall, maize seedlings exposed to VOCs showed a significant increase in disease resistance as indicated by a reduced disease score than that of unexposed infected plants. The VOCs-exposed maize exhibited lower (11.6%) disease incidence compared to the non-inoculated maize (14.1%). Moreover, plants exposed to VOCs displayed visible improvements in biomass, photosynthetic pigments, osmoregulation, and plant antioxidant and defense enzyme activities compared to the healthy but unexposed seedlings. Simultaneous application of RS and VOCs enhanced superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), phenylalanine ammonia lyase (PAL), ascorbate peroxidase (APX), and polyphenol oxidase (PPO) activities by 96.7%, 266.6%, 313.7%, 246.6%, 307%, and 149.7%, respectively, in the roots and by 81.6%, 246.4%, 269.5%, 269.6%, 329%, and 137.6%, respectively, in the shoots, relative to those of the control plants. The binding affinity of the VOCs (2-pentylfuran, 2,3-butanediol, and dimethyl disulfide) with CRZ1 and S9 protein receptors of RS was assessed by deploying in silico methods. Overall, 2-pentylfuran exhibited a binding affinity with both the selected receptors of RS, while 2,3-butanediol and dimethyl disulfide were able to bind S9 protein only. Hence, it can be deduced that S9 protein receptors are more likely the target RS receptors of bacterial VOCs to inhibit the proliferation of RS.
Drought responsiveness in six wheat genotypes: identification of stress resistance indicators
Authors: Guizani Asma , Askri Hend , Amenta Maria Laura , Defez Roberto , Babay Elyes , Bianco Carmen , Rapaná Nicoletta , Finetti-Sialer Mariella , Gharbi Fatma
Published: September 2023

Introduction

Wheat (Triticum aestivum L.) is among the world’s most important staple food crops. In the current climate change scenario, a better understanding of wheat response mechanisms to water stress could help to enhance its productivity in arid ecosystems.

Methods

In this study, water relations, gas exchange, membrane integrity, agronomic traits and molecular analysis were evaluated in six wheat genotypes (D117, Syndiouk, Tunisian durum7 (Td7), Utique, Mahmoudi AG3 and BT) subjected to drought-stress.

Results and discussion

For all the studied genotypes, drought stress altered leaf area, chlorophyll content, stomatal density, photosynthetic rate and water-use efficiency, while the relative water content at turgor loss point (RWC0) remained stable. Changes in osmotic potential at turgor loss point (Ψπ0), bulk modulus of elasticity (Ɛmax) and stomatal regulation, differed greatly among the studied genotypes. For the drought-sensitive genotypes AG3 and BT, no significant changes were observed in Ψπ0, whereas the stomatal conductance (gs) and transpiration rate (E) decreased under stress conditions. These two varieties avoided turgor loss during drought treatment through an accurate stomatal control, resulting in a significant reduction in yield components. On the contrary, for Syndiouk, D117, Td7 and Utique genotypes, a solute accumulation and an increase in cell wall rigidity were the main mechanisms developed during drought stress. These mechanisms were efficient in enhancing soil water uptake, limiting leaf water loss and protecting cells membranes against leakage induced by oxidative damages. Furthermore, leaf soluble sugars accumulation was the major component of osmotic adjustment in drought-stressed wheat plants. The transcriptional analysis of genes involved in the final step of the ABA biosynthesis (AAO) and in the synthesis of an aquaporin (PIP2:1) revealed distinct responses to drought stress among the selected genotypes. In the resistant genotypes, PIP2:1 was significantly upregulated whereas in the sensitive ones, its expression showed only a slight induction. Conversely, the sensitive genotypes exhibited higher levels of AAO gene expression compared to the resistant genotypes. Our results suggest that drought tolerance in wheat is regulated by the interaction between the dynamics of leaf water status and stomatal behavior. Based on our findings, Syndiouk, D117, Utique and Td7, could be used in breeding programs for developing high-yielding and drought-tolerant wheat varieties.