bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring gene-drug interactions for personalized treatment of post-traumatic stress disorder
Authors: Skolariki Konstantina , Vlamos Panagiotis
Published: January 2024

Introduction

Post-Traumatic Stress Disorder (PTSD) is a mental disorder that can develop after experiencing traumatic events. The aim of this work is to explore the role of genes and genetic variations in the development and progression of PTSD.

Methods

Through three methodological approaches, 122 genes and 184 Single Nucleotide Polymorphisms (SNPs) associated with PTSD were compiled into a single gene repository for PTSD. Using PharmGKB and DrugTargetor, 323 drug candidates were identified to target these 122 genes. The top 17 drug candidates were selected based on the statistical significance of the genetic associations, and their promiscuity (number of associated genestargets) and were further assessed for their suitability in terms of bioavailability and drug-like characteristics. Through functional analysis, insights were gained into the biological processes, cellular components, and molecular functions involved in PTSD. This formed the foundation for the next aspect of this study which was to propose an efficient treatment for PTSD by exploring drug repurposing methods.

Results

The main aim was to identify the drugs with the most favorable profile that can be used as a pharmacological approach for PTSD treatment. More in particular, according to the genetic variations present in each individual, the relevant biological pathway can be identified, and the drug candidate proposed will specifically target said pathway, accounting for the personalized aspect of this work. The results showed that the drugs used as off-label treatment for PTSD have favorable pharmacokinetic profiles and the potential drug candidates that arose from DrugTargetor were not very promising. Clozapine showed a promising pharmacokinetic profile and has been linked with decreased psychiatric symptoms. Ambrucin also showed a promising pharmacokinetic profile but has been mostly linked with cancer treatment.
Association between red blood cell distribution width-to-albumin ratio and the prognosis in patients with autoimmune encephalitis: a retrospective cohort study
Authors: Li Dan , Yang Ali , Xia Mingrong , Ma Kai , Zhang Jiewen , Guo Yang , Zang Weizhou
Published: January 2024

Aim

Red blood cell distribution width-to-albumin ratio (RAR) is a combined new indicator reflecting immunology and has been reported to predict the prognosis of inflammation-related diseases and brain diseases. However, the association and predictive value of RAR in the prognosis of patients with autoimmune encephalitis (AE) has not been reported.

Methods

This was a retrospective cohort study, and data were collected from the Henan Provincial People’s Hospital. RAR was categorized according to quartile. The prognosis was assessed using the modified Rankin Scale (mRS), and an mRS score of ≥3 was defined as a poor prognosis. The logistical regression model was used to explore the association between RAR and the prognosis, with results reported as odds ratio (OR) and 95% confidence interval (CI). The predictive value of RAR was evaluated by calculating the area under the receiving operating curve (AUC), sensitivity, specificity, and accuracy.

Results

A total of 175 eligible patients were included for analysis, and 51 patients were identified as having poor prognosis. After adjusting age, cancer, other diseases, histological subtype, antiepileptic therapy, anti-tumor treatment, ICU treatment, and length of stay, RAR in the highest quartile (Q4) was found to be significantly associated with the high odds of poor prognosis (OR = 5.63, 95%CI: 1.98–16.02) compared to RAR in the lowest quartile (Q1). In addition, RAR was identified as a predictor for the prognosis of AE patients (AUC = 0.660, 95%CI: 0.574–0.746).

Conclusion

This study found the close association and predictive value of RAR for the prognosis of AE patients, indicating that RAR might help clinicians identify high-risk populations.
Synonymous variants in the ATP6AP2 gene may lead to developmental and epileptic encephalopathy
Authors: Liang Yan , Wan Lin , Yan Huimin , Liu Xinting , Zhang Jing , Zhu Gang , Yang Guang
Published: January 2024

Objective

To the literature, variants in the ATP6AP2 gene may cause abnormal nervous system development and associated neurological symptoms.

Methods

We report a patient with developmental and epileptic encephalopathy (DEE) carrying an ATP6AP2 c.858G > A (p.Ala286=) synonymous variant. In addition, an overview of reported patients with the same variant were collected and summarized to compare our findings.

Results

The patient started experiencing tonic seizures at 3.5 months of age, and magnetic resonance imaging (MRI) indicated impaired brain white matter development and reduced left hippocampal volume. Furthermore, electroencephalography showed multifocal interictal epileptiform discharges. Treatment with various anti-seizure medications yielded unsatisfactory results, and the disorder eventually developed into epileptic spasms. An in vitro splicing assay for the ATP6AP2 gene mRNA revealed that the variant caused a deletion in exon 8 and a corresponding protein truncation. A review of previously reported ATP6AP2-related DEE patients found that synonymous variants in the ATP6AP2 gene can cause early DEE onset, progressive changes in early-life MRI, and exon skipping in all ATP6AP2-related DEE patients.

Significance

We found that synonymous variants in ATP6AP2 may have significant pathogenicity and are highly correlated with DEE. Due to increased isoform production, ATP6AP2 synonymous variants may cause nervous system developmental disorders by competitively reducing the generation of full-length transcripts, resulting in defects in ATP6AP2-related physiological processes.
The Third Hand of Neurosurgeons – a novel intraoperative malleable adjustable continuous suction tube
Authors: Zhang Jibo , Nie Pan , Wei Zixuan , Xu Chengshi , Li Xiang , Chen Jincao
Published: January 2024

Objective

We designed a novel intraoperative malleable adjustable continuous suction tube to obtain clear surgical fields, reduce intracranial pressure, and lower the temperature of the surgical area.

Methods

This device consists of six parts: continuous suction tube head and cotton patty, suction tube, fixed wire position, fixed clip, spiral plastic pressure regulating valve, and tail. It can continuously extract blood, cerebrospinal fluid, and rinsing solution from surgical fields, with minimal contact and trauma to tissues, nerves, and blood vessels, while also having a negligible impact on the surgeon’s focus and procedure.

Result

The excellent and safe performance (simple, malleable, adjustable, space-saving, inexpensive, safe, and effective) of this device in clearing the operating field has been proven in more than 2000 neurosurgical operative procedures. We encountered no complications associated with this device, such as cerebral hematoma, postoperative low intracranial pressure, or vascular and nerve injuries.

Conclusion

The newly innovated intraoperative malleable adjustable continuous suction tube is effective and safe for microneurosurgery.
Case report: A girl with witnessed sleep apnea
Authors: Wu Shuai , Wang Waner , Han Fang , Xu Liyue
Published: January 2024

Introduction

Pfeiffer syndrome is a rare genetic disorder characterized by craniosynostosis, broad thumbs and big toes, and partial syndactyly of the hands and feet. This case report presents the case of a girl diagnosed with type 2 Pfeiffer syndrome who experienced severe obstructive sleep apnea (OSA).

Case report

The patient had been using an oropharyngeal airway since the age of 4 months due to snoring and witnessed apnea during sleep. At 11 months old, she was referred to our sleep clinic because of growth limitation and gross motor ability issues. Polysomnography (PSG) showed severe obstructive hypopnea before any treatment, and revealed severe central sleep apnea with the oropharyngeal airway in place. Positive airway pressure (PAP) therapy was initiated, which improved both her sleep and gross motor ability.

Conclusion

This case report emphasizes the importance of thorough sleep studies for diagnosing sleep and breathing disorders in Pfeiffer syndrome patients and highlights the effectiveness of PAP therapy in managing these conditions.
Stratification of patients with Menière’s disease based on eye movement videos recorded from the beginning of vertigo attacks and contrast-enhanced MRI findings
Authors: Ueno Yuya , Imai Takao , Higashi-Shingai Kayoko , Ohta Yumi , Sato Takashi , Kamakura Takefumi , Ozono Yoshiyuki , Inohara Hidenori
Published: January 2024

Purpose

Diagnosis of Menière’s disease (MD) relies on subjective factors and the patients diagnosed with MD may have heterogeneous pathophysiologies. This study aims to stratify MD patients using two objective data, nystagmus videos and contrast-enhanced magnetic resonance imaging (CE-MRI).

Methods

This is a retrospective cross-sectional study. According to the Japan Society for Equilibrium Research criteria (c-JSER), adults diagnosed with definite MD and who obtained videos recorded by portable nystagmus recorder immediately following vertigo attacks and underwent CE-MRI of the inner ear were included (ss = 91). Patients who obtained no nystagmus videos, who had undergone sac surgery, and those with long examination intervals were excluded (n = 40).

Results

The gender of the subjects was 22 males and 29 females. The age range was 20–82 y, with a median of 54 y. Endolymphatic hydrops (EH) were observed on CE-MRI in 84% (43 patients). Thirty-one patients had unilateral EH. All of them demonstrated EH on the side of the presence of cochlear symptoms. The number of patients who had both nystagmus and EH was 38. Five patients only showed EH and 5 patients only exhibited nystagmus, while 3 patients did not have either. Of the 43 nystagmus records, 32 showed irritative nystagmus immediately after the vertigo episode. The direction of nystagmus later reversed in 44% of cases over 24 h.

Conclusion

Patients were stratified into subgroups based on the presence or absence of EH and nystagmus. The side with cochlear symptoms was consistent with EH. The c-JSER allows for the diagnosis of early-stage MD patients, and it can be used to treat early MD and preserve hearing; however, this approach may also include patients with different pathologies.
Development of EEG connectivity from preschool to school-age children
Authors: Kang Jiannan , Mao Wenqin , Wu Juanmei , Huang Xinping , Casanova Manuel F. , Sokhadze Estate M. , Li Xiaoli , Geng Xinling
Published: January 2024

Introduction

Many studies have collected normative developmental EEG data to better understand brain function in early life and associated changes during both aging and pathology. Higher cognitive functions of the brain do not normally stem from the workings of a single brain region that works but, rather, on the interaction between different brain regions. In this regard studying the connectivity between brain regions is of great importance towards understanding higher cognitive functions and its underlying mechanisms.

Methods

In this study, EEG data of children (N = 253; 3-10 years old; 113 females, 140 males) from pre-school to schoolage was collected, and the weighted phase delay index and directed transfer function method was used to find the electrophysiological indicators of both functional connectivity and effective connectivity. A general linear model was built between the indicators and age, and the change trend of electrophysiological indicators analyzed for age.

Results

The results showed an age trend for the functional and effective connectivity of the brain of children.

Discussion

The results are of importance in understanding normative brain development and in defining those conditions that deviate from typical growth trajectories.
Role of vitamins A, C, D, E in cancer prevention and therapy: therapeutic potentials and mechanisms of action
Authors: Talib Wamidh H. , Ahmed Jum’AH Dima Abdulraheem , Attallah Zeena Shamil , Jallad Mohanned Sami , Al Kury Lina T. , Hadi Rawan Wamidh , Mahmod Asma Ismail
Published: January 2024

Cancer, a leading global cause of mortality, arises from intricate interactions between genetic and environmental factors, fueling uncontrolled cell growth. Amidst existing treatment limitations, vitamins have emerged as promising candidates for cancer prevention and treatment. This review focuses on Vitamins A, C, E, and D because of their protective activity against various types of cancer. They are essential as human metabolic coenzymes. Through a critical exploration of preclinical and clinical studies via PubMed and Google Scholar, the impact of these vitamins on cancer therapy was analyzed, unraveling their complicated mechanisms of action. Interestingly, vitamins impact immune function, antioxidant defense, inflammation, and epigenetic regulation, potentially enhancing outcomes by influencing cell behavior and countering stress and DNA damage. Encouraging clinical trial results have been observed; however, further well-controlled studies are imperative to validate their effectiveness, determine optimal dosages, and formulate comprehensive cancer prevention and treatment strategies. Personalized supplementation strategies, informed by medical expertise, are pivotal for optimal outcomes in both clinical and preclinical contexts. Nevertheless, conclusive evidence regarding the efficacy of vitamins in cancer prevention and treatment is still pending, urging further research and exploration in this compelling area of study.
Acrylamide formation in air-fried versus deep and oven-fried potatoes
Authors: Navruz-Varlı Semra , Mortaş Hande
Published: January 2024

Introduction

Present study investigates the effects of different home pre-treatment processes and cooking techniques on the acrylamide content of fried potatoes.

Methods

Potato sticks were prepared in two different pre-treatment ways (washing and soaking) and cooked with three other techniques (air frying, deep frying, and oven frying). Acrylamide analyses were performed on cooked potatoes using an LC-MS/MS method.

Results

The highest acrylamide content was found in potatoes cooked using the air fryer (12.19 ± 7.03 μg/kg). This was followed by deep frying (8.94 ± 9.21 μg/kg) and oven frying (7.43 ± 3.75 μg/kg). However, the difference between the acrylamide contents of the potatoes according to the cooking methods was not statistically significant. The acrylamide content of the potatoes that were subjected to soaking in all three ways was lower than the potatoes that were not soaked and only washed. In the deep-frying method, it was found statistically significant that the soaked potatoes contained less acrylamide (p = 0.029).

Discussion

It is important to highlight the relatively low acrylamide levels found in oven-frying, lower than air frying in both washing and soaking groups in the present study. Although air fryers, which have become widely used as an alternative to deep frying in recent years, provide French fries with less oil, their role in the formation of acrylamide should be further investigated.
Hepatoprotective effects of peach gum polysaccharides against alcoholic liver injury: moderation of oxidative stress and promotion of lipid metabolism
Authors: Zhou Bingjie , Liu Pinpin , Yao Xiangao , Cao Huijie , Zhu Hang , Wang Qiao , Liu Yan , Fang Min , Wu Yongning , Gong Zhiyong
Published: January 2024

Natural polysaccharides extracted from plants have received increasing attention due to their rich bioactivity. In our study, peach gum polysaccharides (PGPs) were extracted by water extraction-alcohol precipitation method. PGPs are typical pyranose polysaccharides with a mean molecular weight of 3.68 × 106 g/mol. The antioxidant activity and hepatoprotective capacity of PGPs were studied. In vitro, assays showed that PGPs scavenged DPPH, OH, and O2– in a dose-dependent manner. PGPs exhibited antioxidative properties against alcohol-induced HL7702 cells, as evidenced by the normalization of MDA, SOD, ROS, and GSH levels. To further elucidate the hepatoprotective mechanism of PGPs, we carried out in vivo experiments in male mice. PGPs exerted hepatoprotective effects in alcohol liver disease (ALD) mice by exerting antioxidant effects, decreasing the inflammatory response and modulating lipid metabolism. In addition, metabolomic analysis indicated that PGPs mainly regulate D-glutamine and D-glutamate metabolism, alanine, aspartate and glutamate metabolism, and arginine biosynthesis to promote hepatic metabolism and maintain body functions. Overall, this study revealed that the hepatoprotective mechanism of PGPs against ALD might be associated with the regulation of oxidative stress and lipid metabolism.
Antioxidant, enzymes inhibitory, physicochemical and sensory properties of instant bio-yoghurts containing multi-purpose natural additives
Authors: Irondi Emmanuel Anyachukwu , Bankole Abigael Odunayo , Awoyale Wasiu , Ajani Emmanuel Oladipo , Alamu Emmanuel Oladeji
Published: January 2024

This study aimed to assess the antioxidant, enzyme inhibitory, physicochemical and sensory properties of instant bio-yoghurts containing multi-purpose natural additives. Multi-purpose natural additives were formulated with three natural additives (sweet detar seed, ginger rhizome, and hibiscus calyx flours, as a thickener, flavourant and colourant, respectively) blends at proportions derived from the Design Expert. The additives’ synthetic counterparts were formulated with sodium carboxymethylcellulose, vanilla flavor, and red colourant at the same proportions. After that, yoghurt was produced and the additives blends were incorporated into it either in aqueous extract or flour form, yielding bio-yoghurts designated multi-purpose natural additive extract-containing yoghurt (MNAE-yoghurt), multi-purpose natural additive flour-added yoghurt (MNAF-yoghurt), and their multi-purpose synthetic additives-containing counterparts (MSAE-yoghurt and MSAF-yoghurt). A commercially-available bio-yoghurt served as a control. All the yoghurts were lyophilized to obtain instant bio-yoghurts. Subsequently, bioactive components (total phenolics, tannins, total flavonoids and saponins), antioxidants and enzymes [alpha-amylase, alpha-glucosidase, pancreatic lipase, and angiotensin 1-converting enzyme (ACE)] inhibitory activities, as well as proximate, physicochemical and sensory qualities of the bio-yoghurts were determined. The MNAE-yoghurt and MNAF-yoghurt had higher bioactive constituents, total titratable acid levels, and more potent antioxidant and enzyme inhibitory properties, but a lower pH than their synthetic counterparts and the control. The total phenolics, tannins, total flavonoids and saponins levels of MNAE-yoghurt and MNAF-yoghurt were 14.40 ± 0.24 and 16.54 ± 0.62 mg/g, 1.65 ± 0.04 and 1.74 ± 0.08 mg/g, 4.25 ± 0.03 and 4.40 ± 0.02 mg/g, 0.64 ± 0.01 and 0.66 ± 0.02 mg/g, respectively. Among the natural multi-purpose additives-containing bio-yoghurts, MNAF-yoghurt had higher bioactive constituents and stronger antioxidant and enzymes inhibitory properties. Its α-amylase, α-glucosidase, ACE, and pancreatic lipase IC50 values were 72.47 ± 0.47, 74.07 ± 0.02, 25.58 ± 2.58, and 33.56 ± 29.66 μg/mL, respectively. In contrast, MNAE-yoghurt had the highest protein (13.70 ± 0.85%) and the lowest fat (2.63 ± 0.71%) contents. The sensory attributes of all the bio-yoghurts fell within an acceptable likeness range. Overall, the inclusion of multi-purpose natural additives blends enhanced the instant bio-yoghurts’ nutritional, health-promoting, and sensory qualities.
Evaluation of prognostic significance of lymphovascular space invasion in early stage endometrial cancer: a systematic review and meta-analysis
Authors: Qin Zhao-juan , Wang Yi-si , Chen Ya-li , Zheng Ai , Han Ling
Published: January 2024

Background

Studies evaluating the prognostic significance of lymphovascular space invasion (LVSI) in early stage endometrial cancer (EC) are conflicting.

Objectives

To evaluate whether LVSI identified in stage I EC is associated with worse survival.

Search strategy

A comprehensive literature search of three databases (Embase, PubMed, and Cochrane) was performed up to April 30th 2023.

Selection criteria

Cohort studies that have evaluated the relationship between LVSI and prognosis in patients with stage I EC were included.

Data collection and analysis

Two authors independently assessed the studies for inclusion, extracted the data of recurrence and survival, and conducted meta-analysis using random effects model. Heterogeneity was evaluated by I2 test.

Main results

A total of 15 studies involving 6,705 patients were included in the meta-analysis. The overall pooled rate of LVSI was 14% [95% confidence interval (CI) CI 0.09-0.18] in stage I EC. LVSI was significantly associated with a higher risk of recurrence [odds ratio (OR) = 2.79, 95%CI 2.07-3.77], reduced overall survival (OS) [hazard ratio (HR)=5.19, 95%CI 3.33-8.07] and recurrence free survival (RFS) [HR = 5.26, 95%CI 3.45-8.02] in stage I EC patients. Similarly, LVSI was associated with an increased risk of recurrence [OR= 3.10, 95%CI 2.13-4.51], decreased OS [HR=5.52, 95%CI 2.16-14.09] and RFS [HR = 4.81, 95%CI 2.34-9.91] in stage IA grade 1 or 2 endometrioid carcinoma patients.

Conclusion

The presence of LVSI in stage I EC and in stage IA, grade 1 or 2 endometrioid carcinoma is associated with an increased risk of recurrence, lower OS and RFS.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier 42023425231.
Association between dietary nutrient intake and prevalence of myopia in Korean adolescents: evidence from the 7th Korea National Health and Nutrition Examination Survey
Authors: Kim Jeong-Mee , Choi Yean Jung
Published: January 2024

Background

The rise in myopia prevalence, particularly among adolescents in East Asia, is a cause for concern. While a combination of environmental and genetic factors is understood to contribute to this trend, the role of dietary nutrients is not yet fully clarified.

Objective

To assess the potential association between the intake of specific nutrients and the prevalence of myopia in a large, population-based sample of Korean adolescents.

Methods

Data from 18,077 adolescents (average age: 15.05 ± 1.67 years; 51.7% male, 48.3% female) who participated in the 7th Korea National Health and Nutrition Examination Survey (KNHANES VII, 2016) were analyzed. Refractive error was measured using an auto-refractor-keratometer (KR-8800) without cycloplegia. Dietary intake of 14 nutrients was assessed through a 24-h personalized dietary recall method.

Results

The study revealed a myopia prevalence of 87.6% among the adolescents. Multivariable models adjusted for age, gender, BMI, and other confounding factors indicated that higher intakes of carbohydrates, proteins, cholesterol, sodium, and vitamin B2 were associated with an increased risk of myopia. Conversely, higher intake of vitamin C was found to be associated with a decreased risk.

Conclusion

The findings suggested a potential association between dietary nutrient intake and myopia prevalence in Korean adolescents. While the study did not establish a causal link, the differences in nutrient intake between the myopic and non-myopic groups could indicate that diet plays a role in the development or progression of myopia. Further research is warranted to corroborate these findings and explore the underlying mechanisms.
The influence of prenatal dexamethasone administration before scheduled full-term cesarean delivery on short-term adverse neonatal outcomes: a retrospective single-center cohort study
Authors: Pei Jiaojiao , Chen Jiao
Published: January 2024

Objective

There has been a gradual increase in the prevalence of cesarean section deliveries and more healthcare professionals are considering the prophylactic use of corticosteroids before planned full-term cesarean sections. However, the association between dexamethasone administration before full-term cesarean delivery and short-term adverse neonatal outcomes is unclear. This study analyzed the disparities in short-term adverse neonatal effects in neonates born via full-term elective cesarean delivery with or without antenatal dexamethasone treatment.

Study design

This single-center retrospective cohort study involved neonates aged 37–39 weeks. The primary neonatal outcomes included various short-term adverse events, including neonatal admission to the neonatal intensive care unit, neonatal access to the special care baby unit, transient neonatal respiratory distress, respiratory distress syndrome, and the requirement of intravenous antibiotics or ventilatory support. Multiple logistic regression analysis was used to assess the association between these outcomes and dexamethasone exposure while adjusting for covariates.

Results

Of the 543 neonates included in the study, 121 (22.2%) had been exposed to prenatal dexamethasone. When compared with the control group, the dexamethasone-exposed group exhibited significantly higher rates of transient neonatal respiratory distress, respiratory distress syndrome, administration of intravenous antibiotics, the need for ventilatory support, and longer duration of neonatal hospitalization (P < 0.05). The association between dexamethasone exposure and short-term adverse neonatal outcomes remained significant after adjusting for potential confounders (odds ratio: 12.76, 95% confidence interval: 6.9–23.62, P < 0.001).

Conclusion

The dexamethasone-exposed group had a higher likelihood of experiencing short-term adverse outcomes when compared with non-exposed neonates, suggesting that dexamethasone may have detrimental effects on infants delivered at full term. This implies the importance of exercising caution when contemplating the use of antenatal corticosteroids.
Within-breath oscillometry for identifying exercise-induced bronchoconstriction in pediatric patients reporting symptoms with exercise
Authors: Barreto Mario , Veneroni Chiara , Caiulo Mariaclaudia , Evangelisti Melania , Pompilio Pasquale Pio , Mazzuca Maria Cristina , Raponi Giorgia , Pagani Jacopo , Parisi Pasquale
Published: January 2024

Background

Evaluating oscillometry parameters separately for the inspiratory and expiratory breath phases and their within-breath differences can help to identify exercise-induced bronchoconstriction (EIB) in pediatric outpatients disclosing exercise-induced symptoms (EIS).

Aims

To assess the response in impedance parameters following an exercise challenge in patients reporting EIS.

Methods

Sixty-eight patients reporting EIS (34 asthmatics and 34 suspected of asthma, age mean = 10.8 years, range = 6.0–16.0) underwent an incremental treadmill exercise test. Spirometry was performed at baseline and 1, 5-, 10-, 15-, and 20-min post exercise. Oscillometry was performed at baseline and at 3- and 18-min post exercise. Bronchodilator response to 200 µg albuterol was then assessed. EIB was defined as a forced expiratory volume in 1 s (FEV1) fall ≥10% from baseline. Expiratory and inspiratory resistance (Rrs) and reactance (Xrs), their z-score (Ducharme et al. 2022), and their mean within-breath differences (ΔRrs = Rrsexp-Rrsinsp, ΔXrs = Xrsexp-Xrsinsp) were calculated. Receiver operating characteristic (ROC) curves and their areas (AUCs) were used to evaluate impedance parameters’ performances in classifying EIB.

Results

Asthmatic patients developed EIB more frequently than those suspected of asthma [18/34 (52.9%) vs. 2/34 (5.9%), p < 0.001]. In the 20 subjects with EIB, Rrsinsp, Rrsexp, Xrsinsp, and Xrsexp peaked early (3’), and remained steady except for Xrsinsp, which recovered faster afterward. ΔXrs widened 18 min following the exercise and reversed sharply after bronchodilation (BD) (−1.81 ± 1.60 vs. −0.52 ± 0.80 cmH2O × s/L, p < 0.001). Cutoffs for EIB leading to the highest AUCs were a rise of 0.41 in z-score Rrsinsp (Se: 90.0%, Sp: 66.7%), and a fall of −0.64 in z-score Xrsinsp (Se: 90.0%, Sp: 75.0%). Accepting as having “positive” postexercise oscillometry changes those subjects who had both z-scores beyond respective cutoffs, sensitivity for EIB was 90.0% (18/20) and specificity, 83.3% (40/48).

Conclusion

Oscillometry parameters and their within-breath differences changed markedly in pediatric patients presenting EIB and were restored after the bronchodilator. Strong agreement between z-scores of inspiratory oscillometry parameters and spirometry supports their clinical utility, though larger studies are required to validate these findings in a broader population.
Morroniside induces cardiomyocyte cell cycle activity and promotes cardiac repair after myocardial infarction in adult rats
Authors: Zheng Songyang , Liu Tingting , Chen Mengqi , Sun Fangling , Fei Yihuan , Chen Yanxi , Tian Xin , Wu Zheng , Zhu Zixin , Zheng Wenrong , Wang Yufeng , Wang Wen
Published: January 2024

Introduction: Acute myocardial infarction (AMI) is characterized by the loss of cardiomyocytes, which impairs cardiac function and eventually leads to heart failure. The induction of cardiomyocyte cell cycle activity provides a new treatment strategy for the repair of heart damage. Our previous study demonstrated that morroniside exerts cardioprotective effects. This study investigated the effects and underlying mechanisms of action of morroniside on cardiomyocyte cell cycle activity and cardiac repair following AMI.

Methods: Neonatal rat cardiomyocytes (NRCMs) were isolated and exposed to oxygen-glucose deprivation (OGD) in vitro. A rat model of AMI was established by ligation of the left anterior descending coronary artery (LAD) in vivo. Immunofluorescence staining was performed to detect newly generated cardiomyocytes. Western blotting was performed to assess the expression of cell cycle-related proteins. Electrocardiography (ECG) was used to examine pathological Q waves. Masson’s trichrome and wheat germ agglutinin (WGA) staining assessed myocardial fibrosis and hypertrophy.

Results: The results showed that morroniside induced cardiomyocyte cell cycle activity and increased the levels of cell cycle proteins, including cyclin D1, CDK4, cyclin A2, and cyclin B1, both in vitro and in vivo. Moreover, morroniside reduced myocardial fibrosis and remodeling.

Discussion: In conclusion, our study demonstrated that morroniside stimulates cardiomyocyte cell cycle activity and cardiac repair in adult rats, and that these effects may be related to the upregulation of cell cycle proteins.
Antifungal activity of the repurposed drug disulfiram against Cryptococcus neoformans
Authors: Peng Min , Zhang Chen , Duan Yuan-Yuan , Liu Hai-Bo , Peng Xin-Yuan , Wei Qian , Chen Qi-Ying , Sang Hong , Kong Qing-Tao
Published: January 2024

Fungal infections have become clinically challenging owing to the emergence of drug resistance in invasive fungi and the rapid increase in the number of novel pathogens. The development of drug resistance further restricts the use of antifungal agents. Therefore, there is an urgent need to identify alternative treatments for Cryptococcus neoformans (C. neoformans). Disulfiram (DSF) has a good human safety profile and promising applications as an antiviral, antifungal, antiparasitic, and anticancer agent. However, the effect of DSF on Cryptococcus is yet to be thoroughly investigated. This study investigated the antifungal effects and the mechanism of action of DSF against C. neoformans to provide a new theoretical foundation for the treatment of Cryptococcal infections. In vitro studies demonstrated that DSF inhibited Cryptococcus growth at minimum inhibitory concentrations (MICs) ranging from 1.0 to 8.0 μg/mL. Combined antifungal effects have been observed for DSF with 5-fluorocytosine, amphotericin B, terbinafine, or ketoconazole. DSF exerts significant protective effects and synergistic effects combined with 5-FU for Galleria mellonella infected with C. neoformans. Mechanistic investigations showed that DSF dose-dependently inhibited melanin, urease, acetaldehyde dehydrogenase, capsule and biofilm viability of C. neoformans. Further studies indicated that DSF affected C. neoformans by interfering with multiple biological pathways, including replication, metabolism, membrane transport, and biological enzyme activity. Potentially essential targets of these pathways include acetaldehyde dehydrogenase, catalase, ATP-binding cassette transporter (ABC transporter), and iron-sulfur cluster transporter. These findings provide novel insights into the application of DSF and contribute to the understanding of its mechanisms of action in C. neoformans.
Comparison of knowledge, attitude, practice and predictors of self-medication with antibiotics among medical and non-medical students in Tanzania
Authors: Shitindi Lusajo , Issa Omary , Poyongo Baraka P. , Horumpende Pius Gerald , Kagashe Godeliver A. , Sangeda Raphael Z.
Published: January 2024

Introduction: Self-medication with antibiotics (SMA) is a widespread problem in developing nations, including Tanzania.

Methods: This study compared knowledge, attitudes, practices, and factors influencing antibiotic SMA among medical and non-medical students.

Results: The prevalence of SMA among medical students was 49.1% and 59.2% among non-medical students, respectively. The mean knowledge score of medical students (6.4) was significantly higher (p-value <0.001) than that of non-medical students (5.6). The main factors influencing SMA practices were the availability of antibiotics without a prescription, easy access to pharmacies, and a lack of knowledge about the risks of SMA. This experience was pivotal in influencing medical students to take antibiotics, with a substantial proportion of 67.5% as opposed to 59.4% of non-medical students. Medical students were 1.6 times more likely to self-medicate with antibiotics than non-medical students (Adjusted Odds Ratio (AOR): 1.6; 95% Confidence Interval (CI): 1.2–2.3, p-value = 0.004). Age was also associated with self-medication, with an AOR of 1.1 (95% CI: 1.04–1.2, p-value = 0.006) per year increase in age. Additionally, attitude was associated with self-medication, with an AOR of 1.05 (95% CI: 1.04–1.1, p-value = 0.001) per unit increase in attitude score.

Discussion: No significant associations were found between sex, marital status, having children, year of study, knowledge score, and self-medication with antibiotics. This study emphasizes the importance of educational interventions and public awareness campaigns to promote antimicrobial stewardship, appropriate antibiotic use, and preventing pharmacies from dispensing antibiotics without a prescription.
Ferroptosis: a dual-edged sword in tumour growth
Authors: Zhao Xiangye , Li Xiaoning , Xu Yinghui
Published: January 2024

Ferroptosis, a recently identified form of non-apoptotic cell death, is distinguished by its dependence on iron-triggered lipid peroxidation and accumulation of iron. It has been linked to various disorders, including the development of tumours. Interestingly, ferroptosis appears to exhibit a dual role in the context of tumour growth. This article provides a thorough exploration of the inherent ambivalence within ferroptosis, encompassing both its facilitation and inhibition of tumorous proliferation. It examines potential therapeutic targets associated with ferroptosis, the susceptibility of cancerous cells to ferroptosis, strategies to enhance the efficacy of existing cancer treatments, the interaction between ferroptosis and the immune response to tumours, and the fundamental mechanisms governing ferroptosis-induced tumour progression. A comprehensive understanding of how ferroptosis contributes to tumour biology and the strategic management of its dual nature are crucial for maximizing its therapeutic potential.
The potential influence of melatonin on mitochondrial quality control: a review
Authors: Lei Xudan , Xu Zhenni , Huang Lingxiao , Huang Yujun , Tu Siyu , Xu Lu , Liu Dengqun
Published: January 2024

Mitochondria are critical for cellular energetic metabolism, intracellular signaling orchestration and programmed death regulation. Therefore, mitochondrial dysfunction is associated with various pathogeneses. The maintenance of mitochondrial homeostasis and functional recovery after injury are coordinated by mitochondrial biogenesis, dynamics and autophagy, which are collectively referred to as mitochondrial quality control. There is increasing evidence that mitochondria are important targets for melatonin to exert protective effects under pathological conditions. Melatonin, an evolutionarily conserved tryptophan metabolite, can be synthesized, transported and metabolized in mitochondria. In this review, we summarize the important role of melatonin in the damaged mitochondria elimination and mitochondrial energy supply recovery by regulating mitochondrial quality control, which may provide new strategies for clinical treatment of mitochondria-related diseases.
Role of sodium leak channel (NALCN) in sensation and pain: an overview
Authors: Zhang Donghang , Wei Yiyong
Published: January 2024

The sodium leak channel (NALCN) is widely expressed in the central nervous system and plays a pivotal role in regulating the resting membrane potential (RMP) by mediating the Na+ leak current. NALCN was first reported in 1999, and since then, increasing evidence has provided insights into the structure and functions of NALCN. As an essential component of neuronal background currents, NALCN has been shown to be involved in many important physiological functions, particularly in the respiratory rhythm, as NALCN mutant mice have a severely disrupted respiratory rhythm and die within 24 h of birth. Many patients with NALCN mutations also develop serious clinical syndromes, such as severe hypotonia, speech impairment, and cognitive delay. Recently, emerging studies have clarified the human NALCN structure and revealed additional properties and functions of NALCN. For instance, accumulating evidence highlights that the NALCN is involved in normal sensation and pain. Here, we review the current literature and summarize the role of the NALCN in sensation and pain.
CUTE: A Cryogenic Underground TEst facility at SNOLAB
Authors: Camus Philippe , Corbett Jonathan , Crawford Sean , Dering Koby , Fascione Eleanor , Gerbier Gilles , Germond Richard , Ghaith Muad , Hall Jeter , Hong Ziqing , Kubik Andrew , Mayer Adam , Nagorny Serge , Pakarha Payam , Rau Wolfgang , Scorza Silvia , Underwood Ryan
Published: January 2024

Low-temperature cryogenics open the door for a range of interesting technologies based on features like superconductivity and superfluidity, low-temperature phase transitions or the low heat capacity of non-metals in the milli-Kelvin range. Devices based on these technologies are often sensitive to small energy depositions as can be caused by environmental radiation. The Cryogenic Underground TEst facility (CUTE) at SNOLAB is a platform for testing and operating cryogenic devices in an environment with low levels of background. The large experimental chamber (O(10) L) reaches a base temperature of ∼ 12 mK; it can hold a payload of up to ∼ 20 kg and provides a radiogenic background event rate as low as a few events/kg/keV/day in the energy range below about 100 keV, as well as a negligible muon rate (O1)/month). CUTE was designed and built in the context of the Super Cryogenic Dark Matter Search experiment (SuperCDMS) that uses cryogenic detectors to search for interactions of dark matter particles with ordinary matter. The facility has been used to test SuperCDMS detectors since its commissioning in 2019. In 2021, it was handed over to SNOLAB to become a SNOLAB user facility after the completion of the testing of detectors for SuperCDMS. The facility will be available for projects that benefit from these special conditions, based on proposals assessed for their scientific and technological merits. This article describes the main design features and operating parameters of CUTE.
Higher rating of perceived exertion and lower perceived recovery following a graded exercise test during menses compared to non-bleeding days in untrained females
Authors: Delp Morgan , Chesbro Grant A. , Pribble Brian A. , Miller Ryan M. , Pereira Hugo M. , Black Christopher D. , Larson Rebecca D.
Published: January 2024

The underrepresentation of the female population in exercise sciences could be attributed, at least in part, to difficulty in appropriately accounting for the effects of the menstrual cycle (MC). Previous studies examining the effects of the MC on aerobic performance and subjective measures of aerobic performance show conflicting results.

Purpose: The study examined how the MC affects the objective and subjective measures of aerobic performance within untrained female participants and in comparison with untrained male participants assessed at similar time intervals.

Methods: Twenty-one participants (12 females and 9 males) completed a graded exercise test (GXT) on a cycle ergometer. The female participants were tested during their early follicular (EF; menses), ovulatory (O), and mid-luteal (ML) phases of the MC. The male participants were included as the control group and were randomly assigned to a menstrual cycle phase for each visit. During GXT, maximal oxygen consumption (VO2max), respiratory exchange ratio (RER), maximal heart rate (HRmax), peak blood lactate, and rating of perceived exertion (RPE) were determined. Twenty-four hours post-exercise, the perceived recovery status (PRS) was assessed. The MC phase was estimated using basal body temperature (BBT) in the female participants.

Results: The male participants obtained a higher peak power and VO2max compared to the female participants (p < 0.05). All objective measures of aerobic performance did not significantly differ across the MC phases or time points that were tested. In the untrained female participants, an effect of the MC phase on RPE was found, with RPE being higher at EF (8.92 ± 0.79) compared to O (7.67 ± 1.23; p < 0.05) and ML (7.75 ± 1.06; p < 0.05). In addition, an effect of the MC phase on PRS was found, with perceived recovery being lower at EF (6.83 ± 0.94) compared to O (8.83 ± 1.12) and ML (8.67 ± 0.65; all p < 0.005) for the untrained female participants. No significant differences in RPE and PRS were found between tests in the untrained male participants. The female participants had lower perceived recovery following EF (6.83 ± 0.94) compared with the male participants (9.00 ± 1.00; p < 0.001).

Conclusion: The untrained female participants perceived greater exertion during GXT and impaired recovery following GXT in EF compared to O and ML. These results may be attributed to either a drop in female sex hormone concentrations or discomfort associated with menses. The male participants did not exhibit any changes over time. Future studies using subjective parameters such as perceived exertion to track the internal load of training in the naturally menstruating female population should consider menses.
Synergistic and antagonistic interactions of oxybenzone and ocean acidification: new insight into vulnerable cellular processes in non-calcifying anthozoans
Authors: Morgan Michael B. , Williams Jacob , Breeze Barrett , English Nicholas , Higdon Nathaniel , Onthank Kirt , Qualley Dominic F.
Published: January 2024

Cnidarians face significant threats from ocean acidification (OA) and anthropogenic pollutants such as oxybenzone (BP-3). The convergence of threats from multiple stressors is an important area to investigate because of potential significant synergistic or antagonistic interactions. Real-time quantitative PCR was performed to characterize the expression profiles of twenty-two genes of interest (GOI) in sea anemones (Exaiptasia diaphana) exposed to one of four treatments: 1) 96 h of OA conditions followed by a 4 h exposure to 20 ppb BP-3; 2) Exposure to 4 h 20 ppb BP-3 without 96 h of OA; 3) Exposure to 96 h of OA alone; or 4) laboratory conditions with no exposure to BP-3 and/or OA. These 22 GOIs represent cellular processes associated with proton-dependent transport, sodium-dependent transport, metal cation binding/transport, extracellular matrix, amino acid metabolism/transport, immunity, and/or steroidogenesis. These 22 GOIs provide new insight into vulnerable cellular processes in non-calcifying anthozoans exposed to OA and BP-3. Expression profiles were categorized as synergistic, antagonistic, or additive of BP-3 in the presence of OA. Two GOIs were synergistic. Fifteen GOIs were antagonistic and the remaining five GOIs were additive in response to BP-3 in acidified seawater. A subset of these GOIs appear to be candidate biomarkers for future in situ investigations. In human health, proton-dependent monocarboxylate transporters (MCTs) are promising pharmacological targets and recognized as potential biomarkers. By comparison, these same MCTs appear to be targets of xenobiotic chemical pollutants in cnidarian physiology. In the presence of BP-3, a network of collagen synthesis genes are upregulated and antagonistic in their expression profiles. Cytochrome b561 is a critical protein required for collagen synthesis and in silico modeling demonstrates BP-3 binds in the pocket of cytochrome b561. Understanding the underlying molecular mechanisms of “drug-like” compounds such as BP-3 may lead to a more comprehensive interpretation of transcriptional expression profiles. The collective antagonistic responses of GOIs associated with collagen synthesis strongly suggests these GOIs should be considered candidate biomarkers of effect. GOIs with synergistic and additive responses represent candidate biomarkers of exposure. Results show the effects of OA and BP-3 are interactive with respect to their impact on cnidarians. This investigation offers mechanistic data that supports the expression profiles and underpins higher order physiological responses.
Effects of long-term afforestation on soil water and carbon in the Alxa Plateau
Authors: Zhu Xinglin , Si Jianhua , He Xiaohui , Jia Bing , Zhou Dongmeng , Wang Chunlin , Qin Jie , Liu Zijin
Published: January 2024

Plantations in dry and semi-arid areas significantly affect the soil’s ability to store carbon and maintain a stable water balance. It is yet unclear, though, how planted trees in these regions might impact the soil’s carbon and water levels. As a forest ages, it is unknown how soil water and soil carbon interact with one another. In order to conduct this study, four Saxaul plantations in the Alxa Plateau were chosen, with the neighboring mobile sandy (MS) ground serving as a control. The ages of the plantations ranged from 5 to 46 years. The major topics of the study included the relationship between soil water and soil carbon, changes in the 0-300 cm soil layer’s soil water content (SWC), soil organic carbon (SOC), and soil inorganic carbon (SIC) following afforestation. The findings demonstrated that, in comparison to MS, afforestation considerably increased SOC and SIC stocks. In comparison to MS, the SIC grew by 4.02 kg m-2, 4.12 kg m-2, 5.12 kg m-2, and 6.52 kg m-2 throughout periods of 5 years, 11 years, 22 years, and 46 years, respectively. SOC increased relative to MS by 2.55 kg m-2, 2.91 kg m-2, 3.53 kg m-2, and 4.05 kg m-2. Afforestation, however, also contributed to a considerable decline in deep SWC and an increase in the soil water deficit (SWD). In comparison to MS, the mean SWC values were lower at 5 years, 11 years, 22 years, and 46 years, respectively, by 0.48%, 1.37%, 1.56%, and 4.00%. The increase in soil carbon pool caused by sand afforestation actually came at the expense of a reduction in soil water due to a large negative association between deep SWC, SOC, and SIC. To limit SWC losses and encourage sustainable forest land development, we advocate suitable harvest management practices on forest land.