Browse Articles

Low serum calcium promotes traumatic intracerebral hematoma expansion by the response of immune cell: A multicenter retrospective cohort study

Plasma exchange and radiation resensitize immunotherapy-refractory melanoma: a phase I trial

Abstract Immune checkpoint inhibitors (ICI) are effective for advanced melanoma. However, most develop ICI resistance. Tumor-derived soluble PD-L1 (sPD-L1) and other immunosuppressive factors drive resistance. We hypothesized that therapeutic plasma exchange (TPE) may remove sPD-L1 from circulation and overcome ICI resistance. Patients with metastatic ICI-resistant melanoma and elevated sPD-L1 received radiotherapy to a minority of metastatic lesions, TPE, and ICI re-challenge. Primary endpoints were adverse events and sPD-L1 reduction. Secondary endpoints included overall survival, response, and progression-free survival. Correlative studies included changes in sPD-L1, other immunosuppressive factors, and immune cell phenotypes. Eighteen patients were included. Treatment was well-tolerated, and levels of sPD-L1 were reduced by TPE (mean 78%, p  < 0.0001). Soluble PD-L1 suppression predicted overall survival. The overall response rate was 61% (16.7% complete, 44.4% partial, 22.2% stable, and 16.7% progressing). Changes in peripheral immune cell populations and immunosuppressive factors predicted overall survival. sPD-L1 and other circulating immunoregulatory molecules mediate ICI resistance. TPE can reduce these factors and resensitize ICI-refractory melanoma. Patients with persistent elevation or rapid rebound of sPD-L1 experienced inferior outcomes, suggesting that multiple courses of TPE may be necessary. These findings may apply to other ICI-resistant cancers. Trial registration: NCT04581382, ReCIPE-M1 (Rescuing Cancer Immunotherapy with Plasma Exchange in Melanoma 1).

Species distribution of Cannabis sativa: Past, present and future

Cannabis sativa L. is an annual flowering herb of Eurasian origin that has long been associated with humans. Domesticated independently at multiple locations at different times for different purposes (food, fiber, and medicine), these long-standing human associations have influenced its distribution. However, changing environmental conditions and climatic fluctuations have also contributed to the distribution of the species and define where it is optimally cultivated. Here we explore the shifts in distribution that C. sativa may have experienced in the past and explore the likely shifts in the future. Modeling under paleoclimatic scenarios shows niche expansion and contraction in Eurasia through the timepoints examined. Temperature and precipitation variables and soil variable data were combined for species distribution modeling in the present day and showed high and improved predictive ability together as opposed to when examined in isolation. The five most important variables explaining ~ 65% of the total variation were soil organic carbon content (ORCDRC), pH index measured in water solution (PHIHOX), annual mean temperature (BIO-1), mean temperature of the coldest quarter (BIO-11) and soil organic carbon density (OCDENS) (AUC =  0.934). Climate model projections where efforts are made to curb emissions (RCP45/SSP245) and the business as usual (RCP85/SSP585) models were evaluated. Under projected future climate scenarios, shifts worldwide are predicted with a loss of ~ 43% in suitability areas with scores above 0.4 observed by 2050 and continued but reduced rates of loss by 2070. Changes in habitat range have large implications for the conservation of wild relatives as well as for the cultivation of Cannabis as the industry moves toward outdoor cultivation practices.

Liberal or Restrictive Transfusion Strategy in Aneurysmal Subarachnoid Hemorrhage

The development of a bioanalytical method for the simultaneous analysis of gentamicin and tacrolimus in Rat whole blood using UHPLC–MS/MS

Author Correction: The genetic origin of the Indo-Europeans

Author Correction: Coherent coupling between vortex bound states and magnetic impurities in 2D layered superconductors

A multidisciplinary protocol for reducing excessive and maintaining a healthy body weight in the personalized management of chronic diseases in children and adults

Despite regularly used treatment asthma in both children and adults is not fully controlled. This is more prominent in certain disease subtypes, such as obese asthma. The vast complexity of asthma phenotypes and often overlapping endotypes emphasizes the need for implementing the concept of precision medicine in disease management. In order to address these concerns, an innovative and personalized programme for reducing excessive and maintaining a healthy body weight will be developed by experts from pharmaceutical and food industry (Belupo Inc. and Podravka Inc., Croatia) as well as clinical experts (Srebrnjak Children`s Hospital, Croatia). The programme will involve meals replacement (standard and innovative formulas), dietary program and nutritional counseling, physical activity and other individually tailored measures according specific disease phenotypes and underlying pathophysiological mechanisms in each participant. The outcomes of this study should contribute to better control of the underlying condition, reduction of the frequency and severity of symptoms and, consequently, in the improvement of the participant’s overall quality of life.

Sentinel-Lymph-Node Biopsy in Early-Stage Breast Cancer — Is It Obsolete?

Hunting dog behaviour is a key driver impacting harvest quantity and quality of truffles

Abstract Truffles are an iconic food that have long held high regard. Here we explore the seasonality and eco-physiological interactions affecting truffle quality and quantity across time and space. Collaborating with professional truffle hunters working eight different locations, detailed metrics of 3180 recovered truffles from 236 hunt events and spanning a full fruiting period, were recorded. Contrary to expectations, truffle weight showed no correlation with climate variables, suggesting a limited influence of environmental factors such as temperature and precipitation on truffle size. We also found that truffle maturity and damage from mycophagy were strongly linked, with deeper truffles being more mature but also more susceptible to damage. Finally, we observe that scent-dog behaviour significantly impacts the quantity and quality of recovered truffles, and we address the necessity of considering this in truffle ecophysiology studies. Alongside advances in our biological understanding, we make recommendations of how training methods can be improved to lead to greater detection and quality targeting with immediate socioeconomic impact. These findings highlight the complex interplay between truffle physiology, environmental factors, and human and animal behaviours, emphasizing the need for further considered research to enhance our understanding of truffle biology and to improve truffle cultivation practices.

Identification of a non-inhibitory aptameric ligand to CRL2ZYG11B E3 ligase for targeted protein degradation

Oral pain and comorbidities in an edentulous older population: A k-prototypes cluster analysis

Non-odontogenic oral pain is prevalent among the older people and significantly impacts their quality of life. Non-odontogenic oral pain is usually persistent and accompanied by comorbidities such as psychosocial distress and sleep-related problems, which further complicate pain management. The relationship between non-odontogenic oral pain and comorbidities in the older people, however, has not been well documented. This study aimed to identify the factors associated with non-odontogenic oral pain in an edentulous older population and to subgroup this population based on the patterns of oral pain and its associated factors. In this cross-sectional study, data from completely edentulous individuals in the National Health and Nutrition Examination Survey for the period from 2017 to 2020 March (pre-pandemic) were analysed. Associations and correlations between oral pain and 46 other variables, including demographic, questionnaire, examination and laboratory data, were investigated using Pearson’s chi-squared test and Spearman’s rank correlation test. A p value of < 0.05 was considered statistically significant. Clustering of the data was performed using the k-prototypes algorithm, an unsupervised machine learning. Approximately 42% of the edentulous older people experienced oral pain. ‘Having been told to take daily low-dose aspirin’ was significantly associated with oral pain. Oral pain was positively correlated with depressive symptoms and excessive daytime sleepiness (EDS), and negatively correlated with diastolic blood pressure, red blood cell count, haemoglobin level and haematocrit. The k-prototypes algorithm identified a cluster characterised by frequent oral pain, depression and EDS. This study identified distinct patterns of comorbidities among edentulous older people living with oral pain.

Pembrolizumab in Early-Stage Triple-Negative Breast Cancer

Evaluation of the role of thyroid hormones, vitamin B12, vitamin D3, folic acid and ferritin serum levels in pterygium development

Author Correction: Single nucleotide polymorphisms are associated with strain-specific virulence differences among clinical isolates of Cryptococcus neoformans

Structured follow-up pathway to address unmet needs after transient ischaemic attack and minor stroke (SUPPORT TIA): Feasibility study and process evaluation

Background Care following transient ischaemic attack (TIA) and minor stroke is variable and often leaves patients feeling abandoned and uncertain. We developed a theoretically-informed, multifaceted intervention which comprised nurse-led, structured follow-up at 4 weeks after TIA/minor stroke to identify and address patient needs. This study evaluated the feasibility and acceptability of both the intervention and procedures to inform a future randomised controlled trial. Method We conducted a multicentre, randomised feasibility study with mixed-methods process evaluation (ISRCTN registry reference: ISRCTN39864003). We collected patient reported outcome measures (PROMs) at 1, 12 and 24 weeks and clinical data at baseline and 24 weeks. The process evaluation comprised qualitative interviews with a sub-sample, feedback questionnaires, and observations of intervention delivery. Results We recruited 54 patients over 12 months, achieving 90% of the target sample size (n = 60). PROMs return rates were 94.4% (51/54), 85.2% (46/54) and 71.1% (27/38) at 1, 12, and 24-weeks, respectively. Intervention fidelity was high and the intervention largely aligned with the theoretical underpinnings. The process evaluation illustrated how patients benefitted from the intervention through support they would not have received through usual care. This included direct referral or signposting to support services, information and education, actionable advice, and reassurance about and normalisation of recovery. The trial design was feasible and acceptable for both patients and clinicians. Conclusion Nurse-led, structured follow-up after TIA and minor stroke is feasible, acceptable and valued by patients and clinicians. Our intervention can identify and help address unmet needs. A definitive randomised trial to evaluate intervention effectiveness and cost-effectiveness is feasible and acceptable.

Linear IgA Bullous Dermatosis of Childhood

Study on the mechanical mechanism and control optimization of station subsurface excavation by pile-beam-arch method

A feedback circuitry involving γ-actin, β-actin and nonmuscle myosin-2 A controls tight junction and apical cortex mechanics

Pooled prevalence and associated factors of ECG abnormality among type 2 diabetic patients in the last ten years: Systematic review and meta-analysis

Background Type 2 diabetes mellitus is a global epidemic affecting millions of individuals worldwide. It is considered a chronic metabolic disorder of impaired glucose homeostasis, associated with various long-term complications and poor prognosis of cardiovascular performance. Therefore, this systematic review aimed to determine the pooled prevalence of ECG abnormality among type 2 diabetic patients both in the hospital setting and the general population based on the existing literature. Methods This systematic review has been conducted on the ECG abnormality of patients with Type 2 diabetes. Following the establishment of eligibility criteria, a literature search was conducted using three databases and two search engines. Included articles were then screened, critically appraised, and data extracted independently by two reviewers, and any disagreements were handled by the involvement of a third party. The quality of the included studies had been assessed using the New Castle Ottawa quality assessment scale tool. Pooled prevalence and sensitivity were determined by random effect analysis. Heterogeneity was assessed by Higgins’s I2, and its presence was alleviated by using sub-group analysis. Result Following the identification of 32, 785 studies, 33 publications were eligible for the review with a sample size of 31, 449. The pooled prevalence of ECG abnormality among Type 2 diabetic patients was 31% (95% CI: 25, 36%). It was 26% (95% CI: 1, 51%), and 31% (95% CI: 24, 37%) in the hospital and general/ community population, respectively. Body mass index (AOR =  5.90; 95%CI: 4.96, 7.03), duration of diabetic mellitus (AOR = 9.21; 95%CI: 9.12, 9.31), and being hypertensive (AOR = 5.17; 95%CI: 4.90, 5.46), were significantly associated factors with ECG abnormality among patients with Type 2 diabetic mellitus. Conclusion The pooled prevalence of ECG abnormality among Type 2 diabetic mellitus patients was high, while its magnitude was higher among patients attending hospital settings than in the community. Duration of diabetic mellitus, high body mass index and presence of hypertension were significant factors in this review. Moreover, we advise more longitudinal researches to determine the incidence of ECG abnormality among patients with diabetes considering time duration and sex differences. Ethical consideration Since our study was on the review of secondary data, ethical issues are not necessary