bluuebunny/crossref_metadata_2025 huggingface dataset:
Case report: Rare pulmonary fungal infection caused by Penicillium digitatum: the first clinical report in China
Authors: Shi Xiaojuan , Ye Jiaqing , Liu Peiling , Gao Weili , Feng Zhongjun , Zheng Cuiying , Huang Yinqi , Guo Yumei , Zhang Lijie
Published: July 2024

Penicillium digitatum is a common plant pathogen that causes citrus rot, which is extremely rare in humans. We report a case of a 66-year-old man with a history of consuming large amounts of citrus fruits, smoking for 30 years, and a history of emphysema. He had experienced intermittent coughing with sputum for more than 10 years and was admitted to the hospital due to worsening of symptoms over the past month. Despite antibiotic treatment, his condition did not improve. Subsequently, bronchoalveolar lavage fluid (BALF) was detected by metagenomic next-generation sequencing (mNGS), which showed the presence of P. digitatum. The fungal culture of BALF also indicated the presence of the Penicillium genus. The diagnosis was lung infection caused by P. digitatum, and the patient was treated with itraconazole. The lung infection was controlled. This is the third reported case of invasive pulmonary fungal infection caused by P. digitatum worldwide at the genus level, and the first reported case in China. Although human infections caused by P. digitatum are rare, as an emerging opportunistic pathogen, the detection of this fungus in immunocompromised patients should still be clinically important.
Physiochemical characterization of a potential Klebsiella phage MKP-1 and analysis of its application in reducing biofilm formation
Authors: Das Sayani , Kaledhonkar Sandip
Published: July 2024

The common intestinal pathogen Klebsiella pneumoniae (K. pneumoniae) is one of the leading causes of fatal superbug infections that can resist the effects of commonly prescribed medicines. The uncontrolled use or misuse of antibiotics has increased the prevalence of drug-resistant K. pneumoniae strains in the environment. In the quest to search for alternative therapeutics for treating these drug-resistant infections, bacteriophages (bacterial viruses) emerged as potential candidates for in phage therapy against Klebsiella. The effective formulation of phage therapy against drug-resistant Klebsiella infections demands thorough characterization and screening of many bacteriophages. To contribute effectively to the formulation of successful phage therapy against superbug infections by K. pneumoniae, this study includes the isolation and characterization of a novel lytic bacteriophage MKP-1 to consider its potential to be used as therapeutics in treating drug-resistant Klebsiella infections. Morphologically, having a capsid attached to a long non-contractile tail, it was found to be a siphovirus that belongs to the class Caudoviricetes and showed infectivity against different strains of the target host bacterium. Comparatively, this double-stranded DNA phage has a large burst size and is quite stable in various physiological conditions. More interestingly, it has the potential to degrade the tough biofilms formed by K. pneumoniae (Klebsiella pneumoniae subsp. pneumoniae (Schroeter) Trevisan [ATCC 15380]) significantly. Thus, the following study would contribute effectively to considering phage MKP-1 as a potential candidate for phage therapy against Klebsiella infection.
Advancements and applications of loop-mediated isothermal amplification technology: a comprehensive overview
Authors: Yang Nan , Zhang Han , Han Xiu , Liu Zhifeng , Lu Yan
Published: July 2024

Loop-mediated isothermal amplification (LAMP) is a novel method for nucleic acid detection known for its isothermal properties, high efficiency, sensitivity, and specificity. LAMP employs 4 to 6 primers targeting 6 to 8 regions of the desired sequence, allowing for amplification at temperatures between 60 and 65°C and the production of up to 109 copies within a single hour. The product can be monitored by various methods such as turbidimetry, fluorometry, and colorimetry. However, it faces limitations such as the risk of non-specific amplification, challenges in primer design, unsuitability for short gene sequences, and difficulty in multiplexing. Recent advancements in polymerase and primer design have enhanced the speed and convenience of the LAMP reaction. Additionally, integrating LAMP with technologies like rolling circle amplification (RCA), recombinase polymerase amplification (RPA), and CRISPR-Cas systems has enhanced its efficiency. The combination of LAMP with various biosensors has enabled real-time analysis, broadening its application in point-of-care testing (POCT). Microfluidic technology has further facilitated the automation and miniaturization of LAMP assays, allowing for the simultaneous detection of multiple targets and preventing contamination. This review highlights advancements in LAMP, focusing on primer design, polymerase engineering, and its integration with other technologies. Continuous improvements and integration of LAMP with complementary technologies have significantly enhanced its diagnostic capabilities, making it a robust tool for rapid, sensitive, and specific nucleic acid detection with promising implications for healthcare, agriculture, and environmental monitoring.
The correlation between rapid eye movement sleep behavior disorder and the progress of Parkinson’s disease: a systematic review and meta-analysis
Authors: Zheng Wentao , Pan Yang , Li Kunhua , Tao Keyu , Wang Qiuyu , Yang Yungui
Published: July 2024

Background

This meta-analysis was conducted to evaluate potential differences in symptoms between PD patients with or without RBD.

Methods

A systematic search was conducted in PubMed, Cochrane, Embase, and Web of Science databases (as of August 16, 2023), to identify relevant studies on PD and RBD. Statistical analysis was performed using Stata 15.0. Continuous variables were analyzed using the standardized mean difference (SMD) and 95% confidence interval (95% CI), while count data were assessed using the odds ratio (OR) and 95% CI as statistical effect sizes. Heterogeneity among all included studies was tested; for studies with low heterogeneity (I2 < 50%), a fixed-effects model was used to calculate statistical results. For studies with relatively high heterogeneity (I2 > 50%), a random-effects model was applied, followed by sensitivity and subgroup analyses to identify sources of heterogeneity.

Results

A total of 5,672 subjects were involved in this study. Compared to the NRBD group, the UPDRS-III score in the RBD group was significantly higher (SMD = 0.20, 95% CI: [0.11, 0.29], P < 0.001), and the Hoehn-Yahr score in the RBD group was also significantly higher (SMD = 0.29, 95% CI: [0.03, 0.55], P < 0.001). Patients with PD in the RBD group had more severe cognitive impairments than those in the NRBD group (SMD = −0.30, 95% CI: [−0.48, −0.11], P < 0.001). The incidence of hallucination in PD patients in the RBD group was 3.0 times that of the NRBD group (OR = 3.0, 95% CI: [2.15, 4.20], P = 0.110). PD patients in the RBD group also experienced more severe anxiety symptoms (SMD = 0.13, 95% CI: [−0.26, 0.51], P < 0.001), had higher scores in depression scales (SMD = 0.22, 95% CI: [0.02, 0.43], P < 0.001), and higher scores in sleep disorder scales than those in NRBD group (SMD = 0.10, 95% CI: [−0.11, 0.31], P < 0.001).

Conclusion

Results show PD patients with co-occurring RBD have more severe motor and non-motor symptoms likely due to overlapping affected regions in RBD and PD-related pathology, plus broader neurodegeneration seen in PD patients with RBD.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/#searchadvanced, identifier CRD42023476331.
Identification of deregulated lncRNAs in Alzheimer’s disease: an integrated gene co-expression network analysis of hippocampus and fusiform gyrus RNA-seq datasets
Authors: Filomena Ermes , Picardi Ernesto , Tullo Apollonia , Pesole Graziano , D’Erchia Anna Maria
Published: July 2024

Introduction

The deregulation of lncRNAs expression has been associated with neuronal damage in Alzheimer’s disease (AD), but how or whether they can influence its onset is still unknown. We investigated 2 RNA-seq datasets consisting, respectively, of the hippocampal and fusiform gyrus transcriptomic profile of AD patients, matched with non-demented controls.

Methods

We performed a differential expression analysis, a gene correlation network analysis (WGCNA) and a pathway enrichment analysis of two RNA-seq datasets.

Results

We found deregulated lncRNAs in common between hippocampus and fusiform gyrus and deregulated gene groups associated to functional pathways related to neurotransmission and memory consolidation. lncRNAs, co-expressed with known AD-related coding genes, were identified from the prioritized modules of both brain regions.

Discussion

We found common deregulated lncRNAs in the AD hippocampus and fusiform gyrus, that could be considered common signatures of AD pathogenesis, providing an important source of information for understanding the molecular changes of AD.
Relationship between somatosensory and visuo-perceptual impairments and motor functions in adults with hemiparetic cerebral palsy
Authors: Poitras Isabelle , Campeau-Lecours Alexandre , Mercier Catherine
Published: July 2024

Introduction

Children with cerebral palsy (CP) exhibit a variety of sensory impairments that can interfere with motor performance, but how these impairments persist into adulthood needs further investigation. The objective of this study was to describe the sensory impairments in adults having CP and how they relate to motor impairments.

Methods

Nineteen adults having CP performed a set of robotic and clinical assessments. These assessments were targeting different sensory functions and motor functions (bilateral and unilateral tasks). Frequency of each type of impairments was determined by comparing individual results to normative data. Association between the sensory and motor impairments was assessed with Spearman correlation coefficient.

Results

Impairment in stereognosis was the most frequent, affecting 57.9% of participants. Although less frequently impaired (26.3%), tactile discrimination was associated with all the motor tasks (unilateral and bilateral, either robotic or clinical). Performance in robotic motor assessments was more frequently associated with sensory impairments than with clinical assessments. Finally, sensory impairments were not more closely associated with bilateral tasks than with unilateral tasks.

Discussion

Somatosensory and visuo-perceptual impairments are frequent among adults with CP, with 84.2% showing impairments in at least one sensory function. These sensory impairments show a moderate association with motor impairments.
Dietary free L-glutamate contributes to maintaining a low sodium intake among Vietnamese
Authors: Hien Vu Thi Thu , Tuyen Le Danh , Wakita Andrea , Shikanai Saiko , Hang Le Thi , Anh Nguyen Thi Diep , Nguyet Nguyen Thi Anh , Iwamoto Tamami , Matsumoto Hideki , Uneyama Hisayuki , Son Nguyen Vu , Linh Nguyen Nhat , Yamamoto Shigeru
Published: July 2024

Background

The World Health Organization (WHO) and the Food and Agriculture Organization (FAO) recommend the consumption of less than 2,000 mg of sodium/day to reduce blood pressure and the risk of conditions such as cardiovascular disease and coronary heart disease. The sodium intake among Vietnamese was reported to be 7,200 mg/d or more. Free L-glutamate enhances flavor when it is added to food and improves the taste of sodium-reduced foods.

Objective

This study aims to investigate whether the intake of free L-glutamate-rich seasonings contributes to maintaining a low sodium intake in a cross-over study.

Methods

From a total of 145 subjects, 42 participants were screened for participation in the cross-over design study. Subjects were randomly allocated to the Low free L-glutamate group (Low free L-Gl) and the Normal free L-glutamate group (Normal free L-Gl). Both received a direct educational guideline to reduce sodium intake. The Low free L-Gl group started with a restriction in the variety of free L-glutamate-rich seasonings, and the Normal free L-Gl group had no restriction in the variety of seasonings. Blood pressure was measured at week 0 (baseline), week 2, week 4, and week 6, while body weight, height, urine sodium and potassium excretion, chromogranin-A (CgA pmol/mg protein) from saliva, and free L-glutamate from food were measured at week 0, week 3, and week 6.

Results

In Low free L-Gl, the amount of free L-glutamate in food decreased significantly from baseline to week 6 (p < 0.00), while it did not change in the Normal free L-Gl (p > 0.05). However, the reduction of sodium excretion at week 6 was 22% in Low free L-Gl (5,875 mg/d vs. 4,603 mg/d, p < 0.01) and 46% in Normal free L-Gl (6,107 mg/d vs. 3,277 mg/d, p < 0.00), both lower than the baseline. CgA (pmol/mg protein) did not show any difference between the two groups.

Conclusion

The group with Normal free L-Gl intake showed a 46% reduction in sodium excretion by week 6 compared to the baseline. This suggests that the consumption of L-glutamate-rich seasonings when complemented with direct educational guidelines, can contribute to maintaining a low sodium intake.
Association between intake of flavanones and the overweight/obesity and central obesity in children and adolescents: a cross-sectional study from the NHANES database
Authors: Liu Yangyang , Liu Zhuoqiong , Wu Nan
Published: July 2024

Aim

The prevalence of obesity (Ob), overweight (Ow) and central obesity (CO) in children and adolescents has increased dramatically over the past decades globally. Flavanones have been recently studied as adjuvants for the treatment of obesity. This study was aimed at evaluating the association between intake of flavanones and its subclasses and the Ow/Ob and CO in children and adolescents.

Methods

This cross-sectional study extracted the data of children and adolescents with Ow/Ob and CO from the National Health and Nutrition Examination Survey (NHANES) database for 2007–2010 and 2017–2018. Ow and Ob were defined as a body mass index (BMI) ≥ 85th percentile. CO was defined as a waist circumference (WC) ≥ 90th percentile. The association between intake of flavanones and its subclasses and the Ow/Ob and CO in children and adolescents was determined by weighted univariate and multivariate Logistic regression models adjusted for potential covariates, and odds ratios (ORs) with 95% confidence intervals (CIs) was calculated. To further explore association between intake of flavanones and its subclasses and the Ow/Ob and CO in children and adolescents, subgroup analyses stratified by age, and gender.

Results

Of the total 5,970 children and adolescents, 2,463 (41.2%) developed Ow/Ob and 1,294 (21.7%) patients developed CO. High intake of flavanones, eriodictyol, hesperetin, and naringenin were associated with lower odds of Ow/Ob in children and adolescents. (OR: 0.75, 95%CI: 0.62–0.92, OR: 0.69, 95%CI: 0.55–0.87, OR: 0.69, 95%CI: 0.55–0.87, and OR: 0.76, 95%CI: 0.63–0.92, respectively). In addition, high intake of flavanones, eriodictyol, and naringenin were associated with lower odds of CO in children and adolescents (OR: 0.71, 95%CI: 0.57–0.88, OR: 0.67, 95%CI: 0.51–0.86, and OR: 0.69, 95%CI: 0.55–0.86, respectively). Subgroup analyses showed that among all the different subgroups, high intake of flavanones was associated with lower odds of Ow/Ob and CO in children and adolescents.

Conclusion

A diet loaded with high flavanones were associated with lower odds of Ow/Ob and CO in children and adolescents, and children and adolescents should be encouraged to increase their intake of flavanones.
Thromboelastogram and coagulation function index: relevance for female breast cancer
Authors: Peng Qiongle , Zhu Jinmei , Ren Xiaoling
Published: July 2024

Introduction

Screening and postoperative intervention of breast tumors are critical for the effective diagnosis and treatment of disease development, and reliable diagnostic/screening methods become a key link.

Objective

Thromboelastogram (TEG), routine platelet (PLT) count, and the coagulation function indicators in patients with different breast diseases were determined and analyzed to explore their predictive value in secondary bleeding disorders.

Methods

A total of 131 patients with breast diseases, admitted to Jiangsu University Affiliated Hospital from January 2019 to December 2022, were selected as the research subjects. The detection items were analyzed using the receiver operating curve (ROC) after grouping for secondary bleeding disorders of patients with breast cancer.

Results

The reaction (R) and the coagulation (K) times were lower in the malignant breast disease group, while the coagulation angle (α), maximum amplitude (MA), coagulation index (CI), fibrinogen (FIB), and D-dimer (D-D) were higher than those in the benign breast disease group. The t-tests proved that the MA and FIB values were statistically significant (p < 0.05) in the benign and malignant breast disease groups. The R and K in patients with breast diseases were positively correlated with the activated partial thromboplastin time (aPTT) and D-D, but were negatively correlated with PLT. The α angle was negatively correlated with aPTT and D-D, but was positively correlated with PLT. The MA for PLT function was positively correlated with FIB and PLT. CI was negatively correlated with aPTT, thrombin time (TT), and D-D, but was positively correlated with PLT. ROC curve analysis showed that the CI and α angle had a significant predictive value, whereas the correlation of the other indicators was relatively low.

Conclusion

Coagulation tests showed significant differences in patients with breast cancer, differing from those with benign breast diseases. TEG combined with conventional coagulation indicators is potentially valuable for the prediction of secondary bleeding disorders in patients with breast cancer.
Advances in molecular basis of response to immunotherapy for penile cancer: better screening of responders
Authors: Xu Da-Ming , Chen Ling-Xiao , Zhuang Xiao-Yu , Han Hui , Mo Miao
Published: July 2024

Penile cancer is a rare malignant tumor of the male urinary system. The treatment benefit of standard first-line chemotherapy is not ideal for patients with locally advanced or metastatic lymph nodes. Immunotherapy has brought new treatment strategies and opportunities for patients with penile cancer. At present, clinical studies on immunotherapy for penile cancer have been reported, and the results show that it is effective but not conclusive. With the development of immunotherapy and the progress of molecular research technology, we can better screen the immunotherapy response population and explore new combination treatment regimens to evaluate the best combination regimen and obtain the optimal treatment options, which is also an important research direction for the immunotherapy of penile cancer in the future.
Quantum chemical calculations of nitrosamine activation and deactivation pathways for carcinogenicity risk assessment
Authors: Göller Andreas H. , Johanssen Sandra , Zalewski Adam , Ziegler Verena
Published: July 2024

N-nitrosamines and nitrosamine drug substance related impurities (NDSRIs) became a critical topic for the development and safety of small molecule medicines following the withdrawal of various pharmaceutical products from the market. To assess the mutagenic and carcinogenic potential of different N-nitrosamines lacking robust carcinogenicity data, several approaches are in use including the published carcinogenic potency categorization approach (CPCA), the Enhanced Ames Test (EAT), in vivo mutagenicity studies as well as read-across to analogue molecules with robust carcinogenicity data. We employ quantum chemical calculations as a pivotal tool providing insights into the likelihood of reactive ion formation and subsequent DNA alkylation for a selection of molecules including e.g., carcinogenic N-nitrosopiperazine (NPZ), N-nitrosopiperidine (NPIP), together with N-nitrosodimethylamine (NDMA) as well as non-carcinogenic N-nitrosomethyl-tert-butylamine (NTBA) and bis (butan-2-yl) (nitros)amine (BBNA). In addition, a series of nitroso-methylaminopyridines is compared side-by-side. We draw comparisons between calculated reaction profiles for structures representing motifs common to NDSRIs and those of confirmed carcinogenic and non-carcinogenic molecules with in vivo data from cancer bioassays. Furthermore, our approach enables insights into reactivity and relative stability of intermediate species that can be formed upon activation of several nitrosamines. Most notably, we reveal consistent differences between the free energy profiles of carcinogenic and non-carcinogenic molecules. For the former, the intermediate diazonium ions mostly react, kinetically controlled, to the more stable DNA adducts and less to the water adducts via transition-states of similar heights. Non-carcinogenic molecules yield stable carbocations as intermediates that, thermodynamically controlled, more likely form the statistically preferred water adducts. In conclusion, our data confirm that quantum chemical calculations can contribute to a weight of evidence approach for the risk assessment of nitrosamines.
Advances in the role of resveratrol and its mechanism of action in common gynecological tumors
Authors: Yang Qian , Meng Dandan , Zhang Qingchen , Wang Jin
Published: July 2024

The incidence of common gynecological malignancies remains high, with current treatments facing multiple limitations and adverse effects. Thus, continuing the search for safe and effective oncologic treatment strategies continues. Resveratrol (RES), a natural non-flavonoid polyphenolic compound, is widely found in various plants and fruits, such as grapes, Reynoutria japonica Houtt., peanuts, and berries. RES possesses diverse biological properties, including neuroprotective, antitumor, anti-inflammatory, and osteoporosis inhibition effects. Notably, RES is broadly applicable in antitumor therapy, particularly for treating gynecological tumors (cervical, endometrial, and ovarian carcinomas). RES exerts antitumor effects by promoting tumor cell apoptosis, inhibiting cell proliferation, invasion, and metastasis, regulating tumor cell autophagy, and enhancing the efficacy of antitumor drugs while minimizing their toxic side effects. However, comprehensive reviews on the role of RES in combating gynecological tumors and its mechanisms of action are lacking. This review aims to fill this gap by examining the RES antitumor mechanisms of action in gynecological tumors, providing valuable insights for clinical treatment.
Analysis of eplerenone in the FDA adverse event reporting system (FAERS) database: a focus on overall patient population and gender-specific subgroups
Authors: Guan Xin , Yang Yusi , Li Xinru , Feng Yue , Li Jizhen , Li Xuewen
Published: July 2024

Introduction: Eplerenone is approved for the treatment of hypertension as well as symptomatic heart failure with reduced ejection fraction (HFrEF) following an acute myocardial infarction. However, the adverse events (AEs) have not been systematically analyzed. The aim of this study was to identify adverse drug reactions (ADRs) related to eplerenone using the FDA Adverse Event Reporting System (FAERS) database. By identifying previously unreported AEs, the study could potentially contribute to updating the drug’s label.

Methods: In order to find significant AEs, four algorithms, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN) and Empirical Bayesian Geometric Mean (EBGM), were used to analyze the signal strength of the ADRs connected to eplerenone that were gathered from the FAERS database over the previous 20 years.

Results: From 2004Q1 to 2023Q4, a total of 20, 629, 811 reported cases were gathered from the FAERS database for this study. After processing the data and filtering, 1,874 case reports were analyzed. Of these cases, 1,070 AEs were identified, 128 of which were eplerenone-related ADRs. We investigated the occurrence of ADRs induced by eplerenone in 27 organ systems. Our study showed that the AEs listed in the medication’s package insert correspond with those listed in the literature, including hyperkalemia and increased creatinine. Additionally, the prescription label for eplerenone does not include all system organ class (SOC) terms, like Vascular disorders, hepatobiliary Disorders, etc.

Discussion: The study used multiple algorithms to quantify the signal strength and then identified any previously unrecognized ADRs, further studies are needed to confirm the association of ADRs with eplerenone. The findings of this study may provide important insights into the safety profile of eplerenone, ensure that healthcare providers have up-to-date information about their potential risks and help guide them in the correct use of the drug.
Pericytes: jack-of-all-trades in cancer-related inflammation
Authors: Moro Marianna , Balestrero Federica Carolina , Grolla Ambra A.
Published: July 2024

Pericytes, recognized as mural cells, have long been described as components involved in blood vessel formation, playing a mere supporting role for endothelial cells (ECs). Emerging evidence strongly suggests their multifaceted roles in tissues and organs. Indeed, pericytes exhibit a remarkable ability to anticipate endothelial cell behavior and adapt their functions based on the specific cells they interact with. Pericytes can be activated by pro-inflammatory stimuli and crosstalk with immune cells, actively participating in their transmigration into blood vessels. Moreover, they can influence the immune response, often sustaining an immunosuppressive phenotype in most of the cancer types studied. In this review, we concentrate on the intricate crosstalk between pericytes and immune cells in cancer, highlighting the primary evidence regarding pericyte involvement in primary tumor mass dynamics, their contributions to tumor reprogramming for invasion and migration of malignant cells, and their role in the formation of pre-metastatic niches. Finally, we explored recent and emerging pharmacological approaches aimed at vascular normalization, including novel strategies to enhance the efficacy of immunotherapy through combined use with anti-angiogenic drugs.
Locomotion changes in methamphetamine and amphetamine withdrawal: a systematic review
Authors: Kumar Jaya , Naina Mohamed Isa , Mohamed Rashidi , Ugusman Azizah , Muzaimi Mustapha , Mohamed Wael , Yahaya Mohamad Fairuz , Teoh Seong Lin , Kamaluddin Mohammad Rahim , Abdul Hamid Hafizah , Mehat Muhammad Zulfadli , Shanmugam Prem Kumar
Published: July 2024

Despite extensive preclinical research over the years, a significant gap remains in our understanding of the specific effects of methamphetamine (METH) and amphetamine (AMPH) withdrawal. Understanding these differences could be pivotal to unveiling the unique pathophysiology underlying each stimulant. This may facilitate the development of targeted and effective treatment strategies tailored to the specific characteristics of each substance. Following PRISMA guidelines, this systematic review was conducted to examine alterations in spontaneous locomotor activity, specifically horizontal activity, in animals experiencing withdrawal from extended and repeated administration of AMPH or METH. Original articles were retrieved from four electronic databases, supplemented by a review of the references cited in the published papers. A total of thirty-one full-length articles (n = 31) were incorporated in the analysis. The results indicated that six studies documented a significant increase in horizontal activity among animals, seven studies reported decreased locomotion, and eighteen studies (8 AMPH; 10 METH) reported no significant alterations in the animals’ locomotor activity. Studies reporting heightened locomotion mainly employed mice undergoing withdrawal from METH, studies reporting diminished locomotion predominantly involved rats undergoing withdrawal from AMPH, and studies reporting no significant changes in horizontal activity employed both rats and mice (12 rats; 6 mice). Drug characteristics, routes of administration, animal models, dosage regimens, duration, and assessment timing seem to influence the observed outcomes. Despite more than 50% of papers enlisted in this review indicate no significant changes in the locomotion during the stimulant withdrawal, the unique reactions of animals to withdrawal from METH and AMPH reported by some underscore the need for a more nuanced understanding of stimulant withdrawal.
The factors associated with the modified Fisher grade in patients with aneurysmal subarachnoid hemorrhage
Authors: Zhao Di , Li Yating , Cui Jianzhong
Published: July 2024

Background

Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening medical condition with a high fatality and morbidity rate. There was a substantial link between the modified Fisher grade of aSAH and the neurological function deficit. This study aimed to analyze the factors associated with the modified Fisher grade of aSAH using a machine learning approach.

Methods

A multi-center observational study was conducted. The patients with aSAH were recruited from five tertiary hospitals in China. The volume of hemorrhage in aSAH was measured using the modified Fisher grade scale. The risk factors responsible for the modified Fisher grade of aSAH were analyzed, which include sociodemographic factors, clinical factors, blood index, and ruptured aneurysm characteristics. We built several tree-based machine learning models (XGBoost, CatBoost, LightGBM) for prediction and used grid search to optimize model parameters. To comprehensively evaluate the model, we used Accuracy, Precision, Area Under the Receiver Operating Characteristic Curve (AUROC), Area Under the Precision-Recall Curve (AUPRC), and Brier as evaluation indicators to assess the model performance and select the best model.

Results

A total of 888 patients with aSAH were recruited, of whom 305 with modified Fisher grade of 3 and 4. The results show that the XGBoost model has the highest AUROC of 0.772, and the indicators are better than CatBoost and LightGBM. The feature importance graph shows that the top feature variables include platelet, thrombin time, fibrinogen, preadmission systolic blood pressure, activated partial thromboplastin time, and the time interval between the onset of aSAH and the first-time CT examination.

Conclusion

The factors responsible for the modified Fisher grade of aSAH were identified, which offered valuable insights for future research and clinical intervention. These risk factors should be controlled in the treatment of unruptured aneurysms, and appropriate treatment can be given if necessary to reduce the risk of severe hemorrhage after aneurysm rupture.
Translational insights into the hormetic potential of carbon dioxide: from physiological mechanisms to innovative adjunct therapeutic potential for cancer
Authors: Gaspary João Francisco Pollo , Edgar Lee , Lopes Luis Felipe Dias , Rosa Carmen Brum , Siluk Julio Cezar Mairesse
Published: July 2024

Background

Carbon dioxide (CO2), traditionally viewed as a mere byproduct of cellular respiration, plays a multifaceted role in human physiology beyond simple elimination through respiration. CO2 may regulate the tumor microenvironment by significantly affecting the release of oxygen (O2) to tissues through the Bohr effect and by modulating blood pH and vasodilation. Previous studies suggest hypercapnia (elevated CO2 levels) might trigger optimized cellular mechanisms with potential therapeutic benefits. The role of CO2 in cellular stress conditions within tumor environments and its impact on O2 utilization offers a new investigative area in oncology.

Objectives

This study aims to explore CO2’s role in the tumor environment, particularly how its physiological properties and adaptive responses can influence therapeutic strategies.

Methods

By applying a structured translational approach using the Work Breakdown Structure method, the study divided the analysis into six interconnected work packages to comprehensively analyze the interactions between carbon dioxide and the tumor microenvironment. Methods included systematic literature reviews, data analyses, data integration for identifying critical success factors and exploring extracellular environment modulation. The research used SMART criteria for assessing innovation and the applicability of results.

Results

The research revealed that the human body’s adaptability to hypercapnic conditions could potentially inform innovative strategies for manipulating the tumor microenvironment. This could enhance O2 utilization efficiency and manage adaptive responses to cellular stress. The study proposed that carbon dioxide’s hormetic potential could induce beneficial responses in the tumor microenvironment, prompting clinical protocols for experimental validation. The research underscored the importance of pH regulation, emphasizing CO2 and carbonic acid’s role in modulating metabolic and signaling pathways related to cancer.

Conclusion

The study underscores CO2 as vital to our physiology and suggests potential therapeutic uses within the tumor microenvironment. pH modulation and cellular oxygenation optimization via CO2 manipulation could offer innovative strategies to enhance existing cancer therapies. These findings encourage further exploration of CO2’s therapeutic potential. Future research should focus on experimental validation and exploration of clinical applications, emphasizing the need for interdisciplinary and collaborative approaches to tackle current challenges in cancer treatment.
Not EF skills but play with real toys prevents screen time tantrums in children
Authors: Gavrilova Margarita , Veraksa Nikolay
Published: July 2024

Limiting children’s screen time has become a new parenting challenge. Due to the high attractiveness of media and digital devices, many children experience painful transitions in screen time to other activities. Screen time tantrums is a new concept that describes children’s negative affect screen time limits. Knowing the factors that increase children’s negative reactions will be helpful in parents and educators practice to prevent screen time tantrums or enrich children’s nondigital activities, making them attractive alternatives to the media. Based on theoretical insights into the coping mechanisms of frustration and anger in preschool children, this study was aimed to explore the effects of executive functions skills, family activities, and children’s play behavior with real toys on screen time tantrums. Sample included 654 caregiver-child pairs (M children age = 70.3 months, SD = 4.02). Results confirmed the hypothesis that play behavior with real toys is a stronger preventor of screen time tantrum than EF skills. The findings suggest that supporting play activity in preschool children might help them to avoid strong negative affects due to screen time limitation. The results of this study may be also considered as a support for the theoretical assumptions that play can be considered as a universal way of coping with frustration and anger in childhood.
Trends and factors influencing the mental health of college students in the post-pandemic: four consecutive cross-sectional surveys
Authors: Chen Yinhai , Ke Xiong , Liu Jinfeng , Du Jun , Zhang Jiali , Jiang Xuan , Zhou Tong , Xiao Xiao
Published: July 2024

Background

The long-term impact of COVID-19 on the mental health and well-being of college students, specifically trends over time after full removal of COVID-19 restrictions, has not been well-studied.

Methods

Four consecutive cross-sectional surveys were conducted in December 2022 (N = 689), March 2023 (N = 456), June 2023 (N = 300), and November 2023 (N = 601) at a university in Sichuan Province, China.

Results

The proportion of students with COVID-19 panic decreased from 95.1 to 77.3% (p < 0.001). The prevalence of moderate anxiety and above decreased from 18 to 13.6% (p < 0.001), and the prevalence of moderate and above depression decreased from 33.1 to 28.1% (p < 0.001), while the prevalence of post-traumatic stress disorder (PTSD) increased from 21.5 to 29.6% (p < 0.005). Further, the proportion of suicidal thoughts increased from 7.7 to 14.8% (p < 0.001). Suicidal thoughts and self-injuries were significantly associated with COVID-19 panic, depression, anxiety, and PTSD. Students who reported being in close contact with COVID-19 patients in the past were more likely to develop PTSD. Further, COVID-19-induced panic was a risk factor for self-injury.

Conclusion

One year after the COVID-19 pandemic, the overall mental health of college students was not optimal. Hence, we can conclude that the long-term impacts of COVID-19 on the mental health of college students may have already occurred. To mitigate this impact and prepare for the next major public health event, strengthening college students’ mental health curricula and promoting healthy behaviors among college students should be a priority for universities and education authorities.
Anticipation (second-order motor planning) is stored in memory – processing of grasp postures in a priming paradigm
Authors: Kämpfer Jonas , Vogel Ludwig , Schack Thomas
Published: July 2024

The end-state comfort effect (ESC) describes the tendency to grasp an object with an initial uncomfortable grasp posture in order to achieve a comfortable end posture. The ESC is an example for anticipative processes in manual action. ESC planning is investigated in many studies where this effect is measured in the context of motor observation and motion capture. However, there is little evidence if the anticipative link between different action states, especially between initial grasp postures and comfortable end postures, is represented in memory. The aim of the present study was to investigate whether the perception of a grasp posture holding a bar leads to the activation of action-related representations of grasping actions. For this purpose, a priming paradigm was used in which prime images were shown depicting either a comfortable (overhand grip) or uncomfortable (underhand grip) grasp posture holding a two-colored bar. The subsequently shown target images represented either a comfortable (thumb-up) or uncomfortable (thumb-down) final grasp posture of this grasping action. Due to the different grasp postures in the prime and target, prime-target pairs represented different types of action sequences. Furthermore, physically possible, and physically impossible actions were presented. Participants were asked to react to the top color of the bar shown in the target-picture, whereby the shown grasp posture was irrelevant for this decision. Results showed that reaction times did not differ after presentation of an overhand grip to target pictures showing comfortable or uncomfortable final grasp postures. In contrast, after presentation of an underhand grip in the prime, reactions to target pictures with final comfortable grasp postures were faster compared to target pictures with uncomfortable grasp postures. The effect was only found for the physically possible action. The findings suggest that the perception of the underhand grip leads to cognitive pre-activation of a final action state. The present study suggests that the association between an initial uncomfortable underhand grip and its action effect, in form of a final action state that is consistent with the ESC, is represented in memory. Such motor representation might be important for the anticipation and control of goal-directed grasping.
H-coil repetitive transcranial magnetic stimulation does not improve executive function in patients with chronic peripheral neuropathic pain: a randomized sham-controlled crossover study
Authors: Farnes Nadine , Jacobsen Henrik B. , Stubhaug Audun , Vambheim Sara M.
Published: July 2024

Introduction

Deep rTMS is an increasingly popular noninvasive brain stimulation technique which has shown promise for treating cognitive impairments. However, few studies have investigated the cognitive effects it could exert in patients with chronic peripheral neuropathic pain. Therefore, we aimed to assess the effects of deep rTMS on executive functioning in patients with peripheral neuropathic pain, in a randomized, double-blind crossover trial.

Methods

In total, 17 patients were randomly assigned to receive both active and sham deep H-coil rTMS targeting the primary motor cortex. Each treatment period consisted of five daily rTMS sessions. Selected tests of executive functioning from the CANTAB test battery (paired associates learning, stop signal task, spatial working memory and multitasking test) were performed at baseline, and at 1 week and 3 weeks follow-ups.

Results

We did not find any significant interactions between time and treatment for the measures of executive functioning for the patient group, or for patients with reduced cognition compared to normative means.

Conclusion

High-frequency deep H-coil rTMS targeting the hand area of the primary motor cortex and delivered over 5 consecutive days did not improve executive functioning in patients with chronic peripheral neuropathic pain.

Clinical trial registration

https://clinicaltrials.gov/, identifier NCT05488808.
Acceptance of electronic referrals across the Kingdom of Saudi Arabia: results from a national e-health database
Authors: Alharbi Abdullah A. , Aljerian Nawfal A. , Binhotan Meshary S. , Alghamdi Hani A. , AlOmar Reem S. , Alsultan Ali K. , Arafat Mohammed S. , Aldhabib Abdulrahman , Aloqayli Ahmed I. , Alwahbi Eid B. , Alabdulaali Mohammed K.
Published: July 2024

Introduction

An effective referral system is necessary to ensure quality and an optimum continuum of care. In the Kingdom of Saudi Arabia, an e-referral system known as the Saudi Medical Appointments and Referrals Centre (SMARC), has been fully functioning since 2019. This study aims to explore the rate of medical e-referral request acceptance in the KSA, and to study the factors associated with acceptance.

Methods

This period cross-sectional study utilised secondary collected data from the SMARC e-referral system. The data spans both 2020 and 2021 and covers the entirety of the KSA. Bivariate analyses and binary logistic regression analyses were performed to compute adjusted Odds Ratios (aORs) and 95% confidence intervals.

Results

Of the total 632,763 referral requests across the 2 years, 469,073 requests (74.13%) were accepted. Absence of available machinery was a significant predictor for referral acceptance compared to other reasons. Acceptance was highest for children under 14 with 28,956 (75.48%) and 63,979 (75.48%) accepted referrals, respectively. Patients requiring critical care from all age groups also had the highest acceptance including 6,237 referrals for paediatric intensive care unit (83.54%) and 34,126 referrals for intensive care unit (79.65%). All lifesaving referrals, 42,087 referrals, were accepted (100.00%). Psychiatric patients were observed to have the highest proportion for accepted referrals with 8,170 requests (82.50%) followed by organ transplantations with 1,005 requests (80.92%). Sex was seen to be a significant predictor for referrals, where the odds of acceptances for females increased by 2% compared to their male counterparts (95% CI = 1.01–1.04). Also, proportion of acceptance was highest for the Eastern business unit compared to all other units. External referrals were 32% less likely to be accepted than internal referrals (95% CI = 0.67–0.69).

Conclusion

The current findings indicate that the e-referral system is mostly able to cater to the health services of the most vulnerable of patients. However, there remains areas for health policy improvement, especially in terms of resource allocation.
Urban–rural disparities in minimum acceptable diet intake among children aged 6–23 months in Ethiopia: A multivariable Decomposition analysis of Ethiopian demographic and health survey 2019
Authors: Mohammed Anissa , Tareke Abiyu Abadi , Keleb Awoke , Kebede Natnael , Tsega Yawkal , Endawkie Abel , Kebede Shimels Derso , Mesfin Abera Kaleab , Tilahun Abeje Eyob , Bekele Enyew Ermias , Daba Chala , Asmare Lakew , Bayou Fekade Demeke , Endris Hussien , Arefaynie Mastewal
Published: July 2024

Introduction

The achievement of the minimum acceptable diet intake (MAD) stands at 14% among urban and 10% among rural under-five children in Ethiopia. Consequently, identifying the determinants of the urban–rural gap is vital for advancing Sustainable Development Goals (SDGs), fostering healthier communities, and developing evidence-driven approaches to enhance health outcomes and address disparities.

Objective

The objective of the study was to decompose the urban–rural disparities in minimum acceptable diet intake in Ethiopia using the Ethiopian Mini-Demographic and Health Survey 2019 data.

Method

The study was conducted using the Ethiopian Demographic and Health Survey 2019 report. A total of 1,496 weighted children aged 6–23 months were included using stratified sampling techniques. The main outcome variable minimum acceptable diet was calculated as a combined proportion of minimum dietary diversity and minimum meal frequency. A decomposition analysis was used to analyze the factors associated with the urban–rural discrepancy of minimum acceptable diet intake, and the results were presented using tables and figures.

Result

The magnitude of minimum acceptable diet among children aged 6–23 months in Ethiopia was 11.0%. There has been a significant disparity in the intake of minimum acceptable diet between urban and rural under-five children with 14 and 10%, respectively. Endowment factors were responsible for 70.2% of the discrepancy, followed by 45.1% with behavioral coefficients. Educational status of college and above was responsible for narrowing the gap between urban and rural residents by 23.9% (β = 0.1313, 95% CI: 0.0332–0.245). The number of children in the household and the age of the child between 18 and 23 months were responsible for widening the gap in minimum acceptable diet intake discrepancy between urban and rural residents by 30.7% and 3.36%, respectively (β = −0.002, 95% CI: −0.003 to −0.0011 and β = −30.7, 95% CI: −0.025 – −0.0085). From the effect coefficients, the effect of institutional delivery was responsible for 1.99% of the widening of the gap between urban and rural residents in minimum acceptable diet intake (β = −0.0862, 95% CI: −0.1711 – −0.0012).

Conclusion

There is a significant variation between urban and rural residents in minimum acceptable diet. The larger portion of the discrepancy was explained by the endowment effect. Educational status of mothers with college and above, parity, age of child, and place of delivery were the significant factors contributing to the discrepancy of minimum acceptable diet intake between urban and rural residents.