bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of conventional scoring systems to machine learning models for the prediction of major adverse cardiovascular events in patients undergoing coronary computed tomography angiography
Authors: Ghorashi Seyyed Mojtaba , Fazeli Amir , Hedayat Behnam , Mokhtari Hamid , Jalali Arash , Ahmadi Pooria , Chalian Hamid , Bragazzi Nicola Luigi , Shirani Shapour , Omidi Negar
Published: October 2022

Background

The study aims to compare the prognostic performance of conventional scoring systems to a machine learning (ML) model on coronary computed tomography angiography (CCTA) to discriminate between the patients with and without major adverse cardiovascular events (MACEs) and to find the most important contributing factor of MACE.

Materials and methods

From November to December 2019, 500 of 1586 CCTA scans were included and analyzed, then six conventional scores were calculated for each participant, and seven ML models were designed. Our study endpoints were all-cause mortality, non-fatal myocardial infarction, late coronary revascularization, and hospitalization for unstable angina or heart failure. Score performance was assessed by area under the curve (AUC) analysis.

Results

Of 500 patients (mean age: 60 ± 10; 53.8% male subjects) referred for CCTA, 416 patients have met inclusion criteria, 46 patients with early (<90 days) cardiac evaluation (due to the inability to clarify the reason for the assessment, deterioration of the symptoms vs. the CCTA result), and 38 patients because of missed follow-up were not enrolled in the final analysis. Forty-six patients (11.0%) developed MACE within 20.5 ± 7.9 months of follow-up. Compared to conventional scores, ML models showed better performance, except only one model which is eXtreme Gradient Boosting had lower performance than conventional scoring systems (AUC:0.824, 95% confidence interval (CI): 0.701–0.947). Between ML models, random forest, ensemble with generalized linear, and ensemble with naive Bayes were shown to have higher prognostic performance (AUC: 0.92, 95% CI: 0.85–0.99, AUC: 0.90, 95% CI: 0.81–0.98, and AUC: 0.89, 95% CI: 0.82–0.97), respectively. Coronary artery calcium score (CACS) had the highest correlation with MACE.

Conclusion

Compared to the conventional scoring system, ML models using CCTA scans show improved prognostic prediction for MACE. Anatomical features were more important than clinical characteristics.
Apparent age prediction from faces: A survey of modern approaches
Authors: Agbo-Ajala Olatunbosun , Viriri Serestina , Oloko-Oba Mustapha , Ekundayo Olufisayo , Heymann Reolyn
Published: October 2022

Apparent age estimation via human face image has attracted increased attention due to its numerous real-world applications. Predicting the apparent age has been quite difficult for machines and humans. However, researchers have focused on machine estimation of “age as perceived” to a high level of accuracy. To further improve the performance of apparent age estimation from the facial image, researchers continue to examine different methods to enhance its results further. This paper presents a critical review of the modern approaches and techniques for the apparent age estimation task. We also present a comparative analysis of the performance of some of those approaches on the apparent facial aging benchmark. The study also highlights the strengths and weaknesses of each approach used for apparent age estimation to guide in choosing the appropriate algorithms for future work in the field. The work focuses on the most popular algorithms and those that appear to have been the most successful for apparent age estimation to improve on the existing state-of-the-art results. We based our evaluations on three facial aging datasets, including looking at people (LAP)-2015, LAP-2016, and APPA-REAL, the most popular and publicly available datasets benchmark for apparent age estimation.
Endometriosis-associated infertility: From pathophysiology to tailored treatment
Authors: Bonavina Giulia , Taylor Hugh S.
Published: October 2022

Despite the clinically recognized association between endometriosis and infertility, the mechanisms implicated in endometriosis-associated infertility are not fully understood. Endometriosis is a multifactorial and systemic disease that has pleiotropic direct and indirect effects on reproduction. A complex interaction between endometriosis subtype, pain, inflammation, altered pelvic anatomy, adhesions, disrupted ovarian reserve/function, and compromised endometrial receptivity as well as systemic effects of the disease define endometriosis-associated infertility. The population of infertile women with endometriosis is heterogeneous, and diverse patients’ phenotypes can be observed in the clinical setting, thus making difficult to establish a precise diagnosis and a single mechanism of endometriosis related infertility. Moreover, clinical management of infertility associated with endometriosis can be challenging due to this heterogeneity. Innovative non-invasive diagnostic tools are on the horizon that may allow us to target the specific dysfunctional alteration in the reproduction process. Currently the treatment should be individualized according to the clinical situation and to the suspected level of impairment. Here we review the etiology of endometriosis related infertility as well as current treatment options, including the roles of surgery and assisted reproductive technologies.
Life-stage dependent response of the epiphytic lichen Lobaria pulmonaria to climate
Authors: Di Nuzzo Luca , Canali Giulia , Giordani Paolo , Nascimbene Juri , Benesperi Renato , Papini Alessio , Bianchi Elisabetta , Porada Philipp
Published: October 2022

Lichens are poikilohydric organisms, whose internal water content tends to reflect external humidity conditions. After drying, they can reactivate their metabolic activity through water vapor uptake or liquid water input. Thus, lichen water-related functional traits are important as they are involved in the duration of the hydrated period. Models predicting the effect of environmental conditions on lichens are based mainly on the presence or absence of adult thalli. Nevertheless, ecological conditions required by lichens might vary during their life cycle, for example during propagule establishment or in the first stages of thallus development. Little is known about the different ecological requirements at the different development stages in lichens. In this work, we measured water holding capacity (WHC) and specific thallus mass (STM) of adult and juvenile thalli of the model species Lobaria pulmonaria along a climatic gradient to constrain the process-based model LiBry. The LiBry model allows accounting for the productivity of lichens with different physiological strategies under various environmental conditions. We simulated the activity and performance of adult and juvenile thalli in 9 regions of Italy and Corsica. The model was used to test if adult thalli of L. pulmonaria have a higher survival probability due to their higher aerodynamic resistance. In the current climatic condition, the LiBry model predicts a higher survival probability of adults with decreasing absolute survival rates of both life stages with increasing temperature. Adult thalli also result in having higher active time, STM, and relative growth rate (RGR). We discuss the main implications of our simulation outputs, provide future perspectives and possible implementations of the LiBry model.
Small NRPS-like enzymes in Aspergillus sections Flavi and Circumdati selectively form substituted pyrazinone metabolites
Authors: Lebar Matthew D. , Mack Brian M. , Carter-Wientjes Carol H. , Wei Qijian , Mattison Christopher P. , Cary Jeffrey W.
Published: October 2022

Aspergillus fungi produce mycotoxins that are detrimental to human and animal health. Two sections of aspergilli are of particular importance to cereal food crops such as corn and barley. Aspergillus section Flavi species like A. flavus and A. parasiticus produce aflatoxins, while section Circumdati species like A. ochraceus and A. sclerotiorum produce ochratoxin A. Mitigating these toxins in food and feed is a critical and ongoing worldwide effort. We have previously investigated biosynthetic gene clusters in Aspergillus flavus that are linked to fungal virulence in corn. We found that one such cluster, asa, is responsible for the production of aspergillic acid, an iron-binding, hydroxamic acid-containing pyrazinone metabolite. Furthermore, we found that the asa gene cluster is present in many other aflatoxin- and ochratoxin-producing aspergilli. The core gene in the asa cluster encodes the small nonribosomal peptide synthetase-like (NRPS-like) protein AsaC. We have swapped the asaC ortholog from A. sclerotiorum into A. flavus, replacing its native copy, and have also cloned both asaC orthologs into Saccharomyces cerevisiae. We show that AsaC orthologs in section Flavi and section Circumdati, while only containing adenylation-thiolation-reductase (ATR) domains, can selectively biosynthesize distinct pyrazinone natural products: deoxyaspergillic acid and flavacol, respectively. Because pyrazinone natural products and the gene clusters responsible for their production are implicated in a variety of important microbe-host interactions, uncovering the function and selectivity of the enzymes involved could lead to strategies that ultimately benefit human health.
The protective role of tissue-resident interleukin 17A–producing gamma delta T cells in Mycobacterium leprae infection
Authors: Liu Yan , Shi Chao , Ma Shanshan , Ma Yuelong , Lu Xinyuan , Zhu Jianyu , Yang Degang
Published: October 2022

Mycobacterium leprae is a kind of disease-causing bacteria and results in leprosy in human. Gamma delta (γδ) T cell is a T-cell subset that is presented in both human dermis and epidermis. These cells bridge innate and adaptive immune responses and play critical roles in regulating anti-microbial defense, wound healing, and skin inflammation. Here, we investigated skin resident γδ T cells in patients with leprosy. Our data showed that γδ T cells significantly accumulated in skin lesions of leprosy patients with tuberculoid (TT) form. IL-23 can predominantly stimulate dermal γδ T cells to produce interleukin 17 (IL-17), a cytokine which may lead to disease protection. These γδ T cells expressed a specific set of surface molecules, and majority of these cells were Vδ1+. Also, IL-23 can stimulate the expansion of dermal γδ T cells expansion. Moreover, our results revealed that the transcription factor RORγt was responsible for IL-17A expression in leprosy lesion. Therefore, these data indicated that IL-23–responsive dermal γδ T cells were the major resource of IL-17A production in the skin and could be a potential target in the treatment of leprosy.
Contrasting particle fluxes and composition in a submarine canyon affected by natural sediment transport events and bottom trawling
Authors: Paradis Sarah , Arjona-Camas Marta , Goñi Miguel , Palanques Albert , Masqué Pere , Puig Pere
Published: October 2022

Submarine canyons are important conduits of sediment and organic matter to deep-sea environments, mainly during high-energy natural events such as storms, river floods, or dense shelf water cascading, but also due to human activities such as bottom trawling. The contributions of natural and trawling-induced sediment and organic matter inputs into Palamós Canyon (NW Mediterranean) were assessed from three instrumented moorings deployed in the axis and northern flank of the canyon covering the trawling closure (February) and the trawling season (March-December) of 2017. During the trawling closure, large sediment fluxes with high contents of labile marine organic matter content were registered in the canyon axis, associated to storm resuspension on the shelf that coincided with dense shelf water cascading and high surface water productivity. Although no major natural sediment transport events occurred during the following spring and summer months, near-daily trawling-induced sediment gravity flows were recorded in the northern flank mooring, placed directly below a fishing ground, which sometimes reached the canyon axis. Compositionally, the organic matter transferred by trawling resuspension was impoverished in the most labile biomarkers (fatty acids, amino acids, and dicarboxylic acids) and had a high degree of degradation, which was similar to surficial sediment from the adjacent fishing ground. Trawling resuspended particles masked the transfer of organic matter enriched in labile biomarkers that naturally occur during the quiescent summer months. Overall, bottom trawling enhances the magnitude of particle fluxes while modifying its organic carbon composition, increasing the re-exposure and transfer of degraded organic carbon and potentially affecting benthic communities that rely on the arrival of fresh organic matter.
Synergistic effect of myocardial injury and mid-regional proAdrenomedullin elevation in determining clinical outcomes of SARS-CoV-2 patients
Authors: Spoto Silvia , Mangiacapra Fabio , D’Avanzo Giorgio , Lemme Daniela , Bustos Guillén César , Abbate Antonio , Markley John Daniel , Sambuco Federica , Markley Roshanak , Fogolari Marta , Locorriere Luciana , Lupoi Domenica Marika , Battifoglia Giulia , Costantino Sebastiano , Ciccozzi Massimo , Angeletti Silvia
Published: October 2022

Objective

Coronavirus disease 2019 (COVID-19) is a systemic disease induced by SARS-CoV-2 causing myocardial injury. To date, there are few data on the correlation between mid-regional proAdrenomedullin (MR-proADM) and myocardial injury. The aim of this study was to evaluate whether the association of myocardial injury and elevated mid-regional proAdrenomedullin values could predict mortality of SARS-CoV-2 patients, to offer the best management to COVID-19 patients.

Materials and methods

All patients hospitalized for SARS-CoV-2 infection at the COVID-19 Center of the Campus Bio-Medico of Rome University were included between October 2020 and March 2021 and were retrospectively analyzed. Myocardial injury was defined as rising and/or fall of cardiac hs Troponin I values with at least one value above the 99th percentile of the upper reference limit (≥15.6 ng/L in women and ≥34.2 ng/L in men). The primary outcome was 30-day mortality. Secondary outcomes were the comparison of MR-proADM, CRP, ferritin, and PCT as diagnostic and prognostic biomarkers of myocardial injury. Additionally, we analyzed the development of ARDS, the need for ICU transfer, and length of stay (LOS).

Results

A total of 161 patients were included in this study. Of these, 58 (36.0%) presented myocardial injury at admission. An MR-proADM value ≥ 1.19 nmol/L was defined as the optimal cut-off to identify patients with myocardial injury (sensitivity 81.0% and specificity 73.5%). A total of 121 patients (75.2%) developed ARDS, which was significantly more frequent among patients with myocardial injury (86.2 vs. 68.9%, p = 0.015). The overall 30-day mortality was 21%. Patients with myocardial injury presented significantly higher mortality compared to those without the same (46.6 vs. 6.8%, p < 0.001). When dividing the entire study population into four groups, based on the presence of myocardial injury and MR-proADM values, those patients with both myocardial injury and MR-proADM ≥ 1.19 nmol/L presented the highest mortality (53.2%, p < 0.001). The combination of myocardial injury and MR-proADM values ≥ 1.19 nmol/L was an independent predictor of death (OR = 7.82, 95% CI = 2.87–21.30; p < 0.001).

Conclusion

The study is focused on the correlation between myocardial injury and MR-proADM. Myocardial injury induced by SARS-CoV-2 is strongly associated with high MR-proADM values and mortality.
Virulence factors of Streptococcus anginosus – a molecular perspective
Authors: Kuryłek Aleksandra , Stasiak Monika , Kern-Zdanowicz Izabela
Published: October 2022

Streptococcus anginosus together with S. constellatus and S. intermedius constitute the Streptococcus anginosus group (SAG), until recently considered to be benign commensals of the human mucosa isolated predominantly from oral cavity, but also from upper respiratory, intestinal, and urogenital tracts. For years the virulence potential of SAG was underestimated, mainly due to complications in correct species identification and their assignment to the physiological microbiota. Still, SAG representatives have been associated with purulent infections at oral and non-oral sites resulting in abscesses formation and empyema. Also, life threatening blood infections caused by SAG have been reported. However, the understanding of SAG as potential pathogen is only fragmentary, albeit certain aspects of SAG infection seem sufficiently well described to deserve a systematic overview. In this review we summarize the current state of knowledge of the S. anginosus pathogenicity factors and their mechanisms of action.
Pseudomonas fluorescens group bacterial strains interact differently with pathogens during dual-species biofilm formation on stainless steel surfaces in milk
Authors: Zarei Mehdi , Rahimi Saeid , Saris Per Erik Joakim , Yousefvand Amin
Published: October 2022

In order to develop strategies for preventing biofilm formation in the dairy industry, a deeper understanding of the interaction between different species during biofilm formation is necessary. Bacterial strains of the P. fluorescens group are known as the most important biofilm-formers on the surface of dairy processing equipment that may attract and/or shelter other spoilage or pathogenic bacteria. The present study used different strains of the P. fluorescens group as background microbiota of milk, and evaluated their interaction with Staphylococcus aureus, Bacillus cereus, Escherichia coli O157:H7, and Salmonella Typhimurium during dual-species biofilm formation on stainless steel surfaces. Two separate scenarios for dual-species biofilms were considered: concurrent inoculation of Pseudomonas and pathogen (CI), and delayed inoculation of pathogen to the pre-formed Pseudomonas biofilm (DI). The gram-positive pathogens used in this study did not form dual-species biofilms with P. fluorescens strains unless they were simultaneously inoculated with Pseudomonas strains. E. coli O157:H7 was able to form dual-species biofilms with all seven P. fluorescens group strains, both in concurrent (CI) and delayed (DI) inoculation. However, the percentage of contribution varied depending on the P. fluorescens strains and the inoculation scenario. S. Typhimurium contributed to biofilm formation with all seven P. fluorescens group strains under the CI scenario, with varying degrees of contribution. However, under the DI scenario, S. Typhimurium did not contribute to the biofilm formed by three of the seven P. fluorescens group strains. Overall, these are the first results to illustrate that the strains within the P. fluorescens group have significant differences in the formation of mono-or dual-species biofilms with pathogenic bacteria. Furthermore, the possibility of forming dual-species biofilms with pathogens depends on whether the pathogens form the biofilm simultaneously with the P. fluorescens group strains or whether these strains have already formed a biofilm.
Dissociable effects of oxycodone on behavior, calcium transient activity, and excitability of dorsolateral striatal neurons
Authors: Barry Joshua , Oikonomou Katerina D. , Peng Allison , Yu Daniel , Yang Chenyi , Golshani Peyman , Evans Christopher J. , Levine Michael S. , Cepeda Carlos
Published: October 2022

Opioids are the most common medications for moderate to severe pain. Unfortunately, they also have addictive properties that have precipitated opioid misuse and the opioid epidemic. In the present study, we examined the effects of acute administration of oxycodone, a μ-opioid receptor (MOR) agonist, on Ca2+ transient activity of medium-sized spiny neurons (MSNs) in freely moving animals. Ca2+ imaging of MSNs in dopamine D1-Cre mice (expressing Cre predominantly in the direct pathway) or adenosine A2A-Cre mice (expressing Cre predominantly in the indirect pathway) was obtained with the aid of miniaturized microscopes (Miniscopes) and a genetically encoded Cre-dependent Ca2+ indicator (GCaMP6f). Systemic injections of oxycodone (3 mg/kg) increased locomotor activity yet, paradoxically, reduced concomitantly the number of active MSNs. The frequency of Ca2+ transients was significantly reduced in MSNs from A2A-Cre mice but not in those from D1-Cre mice. For comparative purposes, a separate group of mice was injected with a non-Cre dependent Ca2+ indicator in the cerebral cortex and the effects of the opioid also were tested. In contrast to MSNs, the frequency of Ca2+ transients in cortical pyramidal neurons was significantly increased by oxycodone administration. Additional electrophysiological studies in brain slices confirmed generalized inhibitory effects of oxycodone on MSNs, including membrane hyperpolarization, reduced excitability, and decreased frequency of spontaneous excitatory and inhibitory postsynaptic currents. These results demonstrate a dissociation between locomotion and striatal MSN activity after acute administration of oxycodone.
Stroke health management: Novel strategies for the prevention of recurrent ischemic stroke
Authors: Jiang Lili , Zhou Yu , Zhang Li , Wu Lingling , Shi Haibin , He Bin , Wang Yao , Liu Qianghui , Ji Xueli , Zhang Xintong , Jiang Lei , Sun Hao
Published: October 2022

Objectives

The aim of the study was to assess the effect of the stroke health management model on the prognosis and recurrence of mild to moderate ischemic stroke, guided by the stroke health manager based on the patients' needs. In addition, up-to-date evidence of healthcare resource allocation, planning, and optimization is provided.

Methods

The current research was a retrospective, observational, single-center, history-controlled study with patients divided into two groups, namely, the intervention group and the control group, following the guidance of the stroke health manager. The control group patients received standard medical care during hospitalization, which consisted of advice on healthy lifestyle choices carried out by the bed nurse, but no structured education, WeChat group, or clinical consultation was included. The intervention group patients, in addition to the standard medical care, received health management and health education from the stroke health manager, and after hospital discharge, the patients were followed up over the telephone by the health manager to see if there was any recurrence or readmission.

Results

From 1 January 2018 to 31 December 2020, 382 patients with acute ischemic stroke were enrolled in this study. Through the univariate regression analysis, we found that SHM intervention was associated with a significantly lower risk of recurrence (HR = 0.459). We constructed a nomogram based on the significant variables from the regression analysis and also analyzed the association between the control group and the SHM intervention group among all subgroups using the Cox proportional hazards model to assess the effect of the stroke health management model. Most patients in this study had a total risk point between 170 and 270. The C-index value was 0.76, and the time-dependent AUC for predicting recurrence was >0.7.

Conclusion

The stroke health manager-guided management model based on patients' needs can better control the risk factors of stroke and significantly reduce the recurrence rate of mild to moderate ischemic stroke within 1 year.
Anti-glycine receptor antibody-positive progressive encephalomyelitis with rigidity and myoclonus initially presenting with one-sided stiff face: A case report
Authors: Irie Ken-Ichi , Tateishi Takahisa , Moritaka Taiga , Sakurada Naonori , Kikuchi Shinsuke , Taniwaki Takayuki
Published: October 2022

Background

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a subtype of stiff-person syndrome, a rare cerebrospinal disease that causes brainstem symptoms, myoclonus, muscle rigidity, and hyperekplexia.

Case presentation

A 71-year-old man experienced left-sided stiff face, and was subsequently admitted to our hospital because of the appearance of left-dominant lower limb myoclonus. Muscle rigidity followed 3 days later. Magnetic resonance imaging revealed no abnormality. An electrophysiological examination showed a toughness of the antagonistic muscle following evocation of the Achilles tendon reflex, and a tonic phenomenon affecting the left facial muscles during the blink reflex. The patient's serum was positive for anti-glycine receptor (anti-GlyR) antibody, suggesting PERM. The patient was administered steroids, immunoglobulin therapy, and immunosuppressive drugs. He gradually improved after these therapies and became able to walk using a walker.

Conclusions

We conclude that this was a rare case of anti-GlyR antibody-positive PERM with unilateral brainstem symptoms, myoclonus, and muscle rigidity.
Alcohol-induced brain deficit in alcohol dependence
Authors: Wang Yanping , Sun Bo
Published: October 2022

Although numerous adverse effects of alcohol addiction on health, behavior, and brain function were widely reported, the neurobiological mechanism of alcohol dependence remains largely unknown. In this study, a total of twenty-nine patients with alcohol dependence and twenty-nine status-matched normal controls (NCs) were recruited. Percent amplitude of fluctuation (PerAF) was applied to identify alcohol-related brain activity deficits. We found that alcohol dependence was associated with widespread differences in the left orbitofrontal cortex, right higher visual cortex, right supramarginal gyrus, right postcentral gyrus, and bilateral cerebellum posterior lobe with decreased PerAF, but no brain areas with increased PerAF differences were found. ROC curve showed that decreased PerAF revealed extremely high discriminatory power with a high AUC value of 0.953, as well as a high degree of sensitivity (96.6%) and specificity (86.2%), in distinguishing patients with alcohol dependence from NCs. In the alcohol dependence group, the amount of daily alcohol consumption showed significant negative correlations with the right cerebellum posterior lobe and right higher visual cortex. These findings suggest that the cerebellar-visual-orbitofrontal circuit was disturbed by alcohol dependence. The proposed new method of PerAF may be served as a potential biomarker to identify the regional brain activity deficits of alcohol dependence.
Causal relationship among obesity and body fat distribution and epilepsy subtypes
Authors: Zhou Kaiping , Yang Huan , Chen Ruomeng , Wang Weiping , Qu Zhenzhen
Published: October 2022

Objective

The observational studies indicate an association between obesity and epilepsy, but it is unclear whether such an association responds to causality. The objective of this study was to determine the causal relationship between obesity and fat distribution and epilepsy subtypes based on waist circumference, hip circumference (HP), waist-hip ratio (WHR), and body mass index (BMI).

Methods

A two-sample Mendelian randomization study was conducted separately for the four indicators of obesity and epilepsy and its seven subtypes, with reverse Mendelian randomization and multivariate Mendelian randomization for significant outcomes.

Results

A two-sample Mendelian randomized analysis informed us that waist circumference was a risk factor for juvenile myoclonic epilepsy (beta = 0.0299, P = 4.60 × 10−3). The increase in hip circumference increased the risk of juvenile myoclonic epilepsy and epilepsy, with effect values of 0.0283 (P = 2.01 × 10−3) and 0.0928 (P = 1.40 × 10−2), respectively. Furthermore, children with a higher BMI exhibit a higher risk of epilepsy (beta = 0.0148 P = 1.05 × 10−3). The reverse Mendelian randomization study revealed that childhood absence epilepsy increased its BMI (beta = 0.8980, P = 7.52 × 10−7), and juvenile myoclonic epilepsy increased its waist circumference (beta = 0.7322, P = 3.26 × 10−2). Multivariate Mendelian randomization revealed that an increase in hip circumference and waist-hip ratio increased the risk of juvenile myoclonic epilepsy, with an effect value of 0.1051 (P = 9.75 × 10−4) and 0.1430 (P = 3.99 × 10−3), respectively, while an increase in BMI and waist circumference instead decreased their risk, with effect values of −0.0951 (P = 3.14 × 10−2) and−0.0541 (P = 1.71 × 10−2). In contrast, multivariate Mendelian randomization for childhood absence epilepsy and epilepsy did not identify any independent risk factors.

Significance

Our findings provide novel evidence in favor of obesity as a risk factor for epilepsy and waist circumference as a risk factor for juvenile myoclonic epilepsy. Increased hip circumference confers an elevated risk of juvenile myoclonic epilepsy and epilepsy (all documented cases), and a high BMI increases the risk of childhood absence epilepsy. With this, new insights are provided into the energy metabolism of epilepsy, which supports further nutritional interventions and the search for new therapeutic targets.
Reversing painful and non-painful diabetic neuropathy with the capsaicin 8% patch: Clinical evidence for pain relief and restoration of function via nerve fiber regeneration
Authors: Anand Praveen , Privitera Rosario , Donatien Philippe , Fadavi Hassan , Tesfaye Solomon , Bravis Vassiliki , Misra V. Peter
Published: October 2022

Introduction

Current oral treatments for pain in diabetic peripheral neuropathy (DPN) do not affect the progression of DPN i.e., “disease modification.” We assessed whether Capsaicin 8% patch treatment can provide pain relief and also restore nerve density and function via nerve regeneration, in both painful (PDPN) and non-painful (NPDPN) diabetic peripheral neuropathy.

Methods

50 participants with PDPN were randomized to receive Capsaicin 8% patch Qutenza with Standard of Care (SOC) (PDPN Q+SOC group), or SOC alone (PDPN SOC group). Pain symptoms were assessed with a diary (Numerical Pain Rating Scale, NRPS) and questionnaires. Investigations included quantitative sensory testing (QST) and distal calf skin biopsies, at baseline and 3 months after baseline visit; subsequent options were 3-monthly visits over 1 year. 25 participants with NPDPN had tests at baseline, and 3 months after all received Capsaicin 8% patch treatment.

Results

At 3 months after baseline, PDPN Q+SOC group had reduction in NPRS score (p = 0.0001), but not PDPN SOC group. Short-Form McGill Pain Questionnaire (SF-MPQ) showed significant reductions in scores for overall and other pain descriptors only in the PDPN Q+SOC group. Warm perception thresholds were significantly improved only in the PDPN Q+SOC group (p = 0.02), and correlated with reduction in SF-MPQ overall pain score (p = 0.04). NPDPN Q+SOC group did not report pain during the entire study. Density of intra-epidermal nerve fibers (IENF) with PGP9.5 was increased at 3 months in PDPN Q+SOC (p = 0.0002) and NPDPN Q+SOC (p = 0.002) groups, but not in the PDPN SOC group. Increased sub-epidermal nerve fibers (SENF) were observed with GAP43 (marker of regenerating nerve fibers) only in PDPN Q+SOC (p = 0.003) and NPDPN Q+SOC (p = 0.0005) groups. Pain relief in the PDPN Q+SOC group was correlated with the increased PGP9.5 IENF (p = 0.0008) and GAP43 (p = 0.004), whereas those with lack of pain relief showed no such increase; in some subjects pain relief and increased nerve fibers persisted over months. PGP9.5 IENF increase correlated with axon-reflex vasodilatation in a NPDPN Q+SOC subset (p = 0.006).

Conclusions

Capsaicin 8% patch can provide pain relief via nerve regeneration and restoration of function in DPN (disease modification). It may thereby potentially prevent diabetic foot complications, including ulcers.
STEPS 4.0: Fast and memory-efficient molecular simulations of neurons at the nanoscale
Authors: Chen Weiliang , Carel Tristan , Awile Omar , Cantarutti Nicola , Castiglioni Giacomo , Cattabiani Alessandro , Del Marmol Baudouin , Hepburn Iain , King James G. , Kotsalos Christos , Kumbhar Pramod , Lallouette Jules , Melchior Samuel , Schürmann Felix , De Schutter Erik
Published: October 2022

Recent advances in computational neuroscience have demonstrated the usefulness and importance of stochastic, spatial reaction-diffusion simulations. However, ever increasing model complexity renders traditional serial solvers, as well as naive parallel implementations, inadequate. This paper introduces a new generation of the STochastic Engine for Pathway Simulation (STEPS) project (http://steps.sourceforge.net/), denominated STEPS 4.0, and its core components which have been designed for improved scalability, performance, and memory efficiency. STEPS 4.0 aims to enable novel scientific studies of macroscopic systems such as whole cells while capturing their nanoscale details. This class of models is out of reach for serial solvers due to the vast quantity of computation in such detailed models, and also out of reach for naive parallel solvers due to the large memory footprint. Based on a distributed mesh solution, we introduce a new parallel stochastic reaction-diffusion solver and a deterministic membrane potential solver in STEPS 4.0. The distributed mesh, together with improved data layout and algorithm designs, significantly reduces the memory footprint of parallel simulations in STEPS 4.0. This enables massively parallel simulations on modern HPC clusters and overcomes the limitations of the previous parallel STEPS implementation. Current and future improvements to the solver are not sustainable without following proper software engineering principles. For this reason, we also give an overview of how the STEPS codebase and the development environment have been updated to follow modern software development practices. We benchmark performance improvement and memory footprint on three published models with different complexities, from a simple spatial stochastic reaction-diffusion model, to a more complex one that is coupled to a deterministic membrane potential solver to simulate the calcium burst activity of a Purkinje neuron. Simulation results of these models suggest that the new solution dramatically reduces the per-core memory consumption by more than a factor of 30, while maintaining similar or better performance and scalability.
Validity and reliability of a semi-quantitative food frequency questionnaire for assessing dietary vitamin D and calcium intakes in Iranian childbearing age women
Authors: Moridpour Amir Hossein , Rafraf Maryam , Sarbakhsh Parvin , Asghari Somayyeh , Molani-Gol Roghayeh , Asghari-Jafarabadi Mohammad
Published: October 2022

This study aimed to examine the validity and reliability of a semi-quantitative food frequency questionnaire (FFQ) designed to estimate dietary vitamin D and Calcium (Ca) intakes in a sample of Iranian childbearing age women. An 87-item FFQ was developed and 84 healthy childbearing age women completed it. FFQ was validated by comparing its results with the 24-h dietary recall (24-h recall) and serum 25-hydroxyvitamin D (S-25(OH)D) as the references methods. The FFQ was completed for the second time after 4 weeks to assess the reliability of the questionnaire. Data were analyzed using spearman’s correlation, cross-classification analysis, Bland–Altman plots, the weighted κ, intraclass classification, and the method of triads. Spearman’s correlations between vitamin D and Ca intakes by the FFQ and 24-h recalls and between vitamin D intakes and S-25(OH)D were significant (r: 0.706, r: 0.959, and r: 0.682, respectively, all, P < 0.001). Cross-classification for vitamin D and Ca between two dietary methods and for vitamin D intake of FFQ and S-25(OH)D demonstrated that most of the quartiles were categorized into the same or adjacent quartiles. The Bland Altman plots for these nutrients also demonstrated good agreement. For vitamin D, the validity coefficients (VCs) calculated by the method of the triad for three methods were in the range of 0.808–0.843. The weighted κ for agreement of vitamin D and Ca by FFQ1 and FFQ2 were 0.18 and 0.638, respectively. The findings indicated that the developed FFQ has acceptable validity for estimating vitamin D and Ca. Its reliability for Ca was stronger than vitamin D.
Comprehensive characterization of RNA cargo of extracellular vesicles in breast cancer patients undergoing neoadjuvant chemotherapy
Authors: Sadovska Lilite , Zayakin Pawel , Eglītis Kristaps , Endzeliņš Edgars , Radoviča-Spalviņa Ilze , Avotiņa Elīza , Auders Jānis , Keiša Laura , Liepniece-Karele Inta , Leja Mārcis , Eglītis Jānis , Linē Aija
Published: October 2022

Extracellular vesicles (EVs) are g7aining increased attention as carriers of cancer-derived molecules for liquid biopsies. Here, we studied the dynamics of EV levels in the plasma of breast cancer (BC) patients undergoing neoadjuvant chemotherapy (NAC) and explored the relevance of their RNA cargo for the prediction of patients’ response to the therapy. EVs were isolated from serial blood samples collected at the time of diagnosis, at the end of NAC, and 7 days, 6, and 12 months after the surgery from 32 patients with locally advanced BC, and 30 cancer-free healthy controls (HCs) and quantified by nanoparticle tracking analysis. The pre-treatment levels of EVs in BC patients were higher than in HCs, significantly increased during the NAC and surgery, and decreased to the levels found in HCs 6 months after surgery, thus showing that a substantial fraction of plasma EVs in BC patients are produced due to the disease processes and treatment. RNA sequencing analysis revealed that the changes in the EV levels were associated with the alterations in the proportions of various RNA biotypes in EVs. To search for RNA biomarkers that predict response to the NAC, patients were dichotomized as responders and non-responders based on Miller-Payne grades and differential expression analyses were carried out between responders and non-responders, and HCs. This resulted in the identification of 6 miRNAs, 4 lncRNAs, and 1 snoRNA that had significantly higher levels in EVs from non-responders than responders at the time of diagnosis and throughout the NAC, and significantly lower levels in HCs, thus representing biomarkers for the prediction of response to NAC at the time of diagnosis. In addition, we found 14 RNAs representing piRNA, miRNA, lncRNA, snoRNA, and snRNA biotypes that were induced by NAC in non-responders and 2 snoRNAs and 1 piRNA that were induced by NAC in patients with early disease progression, thus warranting further functional studies on their role in chemoresistance and metastasis.
Case Report: 68Ga-FAPI PET/CT, a more advantageous detection mean of gastric, peritoneal, and ovarian metastases from breast cancer
Authors: Li Tianyue , Jiang Xiaojing , Zhang Zhaoqi , Chen Xiaolin , Wang Jianfang , Zhao Xinming , Zhang Jingmian
Published: October 2022

Breast cancer is the most common malignant tumor in adult women. Its common metastatic sites are lymph nodes, bones, lungs, the liver, and the brain. It is so rare for a patient with breast cancer to have metastases of the gastrointestinal tract, peritoneum, and ovary at the same time that the clinical reporting rate is low. We present a case of a 61-year-old woman who underwent right mastectomy and chemoradiotherapy 3 years ago because of mixed invasive ductal-lobular breast cancer. This time, she came to the hospital due to the symptom of stomach discomfort for 2 weeks. The gastroscopy biopsy result showed gastric metastasis from breast cancer. Then, 18F-FDG imaging and 68Ga-FAPI PET/CT imaging were performed for further diagnosis; 68Ga-FAPI PET/CT demonstrated a significantly elevated FAPI activity in the thickened gastric wall, peritoneum, and bilateral adnexal areas, which was superior to that of 18F-FDG. Finally, a biopsy of suspicious lesions was taken for pathological and histochemical examination, which confirmed that, in addition to the gastric metastasis, the peritoneum and bilateral ovaries were all consistent with metastatic breast cancer.
Updates in combined approaches of radiotherapy and immune checkpoint inhibitors for the treatment of breast cancer
Authors: Jungles Kassidy M. , Holcomb Erin A. , Pearson Ashley N. , Jungles Kalli R. , Bishop Caroline R. , Pierce Lori J. , Green Michael D. , Speers Corey W.
Published: October 2022

Breast cancer is the most prevalent non-skin cancer diagnosed in females and developing novel therapeutic strategies to improve patient outcomes is crucial. The immune system plays an integral role in the body’s response to breast cancer and modulating this immune response through immunotherapy is a promising therapeutic option. Although immune checkpoint inhibitors were recently approved for the treatment of breast cancer patients, not all patients respond to immune checkpoint inhibitors as a monotherapy, highlighting the need to better understand the biology underlying patient response. Additionally, as radiotherapy is a critical component of breast cancer treatment, understanding the interplay of radiation and immune checkpoint inhibitors will be vital as recent studies suggest that combined therapies may induce synergistic effects in preclinical models of breast cancer. This review will discuss the mechanisms supporting combined approaches with radiotherapy and immune checkpoint inhibitors for the treatment of breast cancer. Moreover, this review will analyze the current clinical trials examining combined approaches of radiotherapy, immunotherapy, chemotherapy, and targeted therapy. Finally, this review will evaluate data regarding treatment tolerance and potential biomarkers for these emerging therapies aimed at improving breast cancer outcomes.
Prediction of breast cancer-related lymphedema risk after postoperative radiotherapy via multivariable logistic regression analysis
Authors: Kim Jae Sik , Kim Jin Ho , Chang Ji Hyun , Kim Do Wook , Shin Kyung Hwan
Published: October 2022

Purpose

We identified novel clinical and dosimetric prognostic factors affecting breast cancer-related lymphedema after postoperative radiotherapy (RT) and developed a multivariable logistic regression model to predict lymphedema in these patients.

Methods and materials

In total, 580 patients with unilateral breast cancer were retrospectively reviewed. All patients underwent breast surgery and postoperative RT with or without systemic treatment in 2015. Among the 580 patients, 532 with available RT plan data were randomly divided into training (n=372) and test (n=160) cohorts at a 7:3 ratio to generate and validate the lymphedema prediction models, respectively. An area under the curve (AUC) value was estimated to compare models.

Results

The median follow-up duration was 5.4 years. In total, 104 (17.9%) patients experienced lymphedema with a cumulative incidence as follows: 1 year, 10.5%; 3 years, 16.4%; and 5 years, 17.6%. Multivariate analysis showed that body mass index ≥25 kg/m2 (hazard ratio [HR] 1.845), dissected lymph nodes ≥7 (HR 1.789), and taxane-base chemotherapy (HR 4.200) were significantly associated with increased lymphedema risk. Conversely, receipt of RT at least 1 month after surgery reduced the risk of lymphedema (HR 0.638). A multivariable logistic regression model using the above factors, as well as the minimum dose of axillary level I and supraclavicular lymph node, was created with an AUC of 0.761 and 0.794 in the training and test cohorts, respectively.

Conclusions

Our study demonstrated that a shorter interval from surgery to RT and other established clinical factors were associated with increased lymphedema risk. By combining these factors with two dosimetric parameters, we propose a multivariable logistic regression model for breast cancer-related lymphedema prediction after RT.
Clinical significance of MMP-9 overexpression in endometrial cancer: A PRISMA-compliant meta-analysis
Authors: Li Xia , Zha Li , Li Bo , Sun Rong , Liu Jianhua , Zeng Hongwei
Published: October 2022

Objective

Several studies have found that MMP-9, one of the extracellular matrix-degrading proteinases, was involved in EC’s (endometrial cancer) clinical progression and prognosis. However, the results involving the associations of MMP-9 expression with risk, clinical features and prognosis of EC were conflicting. Therefore, we performed a systematic review and meta-analysis to clarify the correlation of MMP-9 expression with EC.

Methods

Relative studies involving the associations between MMP-9 expression and EC were retrieved from PubMed, Embase, Web of Science and CNKI (China National Knowledge Infrastructure) electronic databases. OR (odds ratio) with 95% CI (confidence interval) was applied to evaluate the associations of MMP-9 expression with risk and clinical features of EC. Furthermore, we evaluated the role of MMP-9 expression in prognosis of EC using HR and 95% CI. The funnel plots and Begg test were used to assess the publication bias.

Results

A total of 28 eligible studies were acquired from Pubmed, Embase, Web of science and CNKI databases. We found MMP-9 overexpression was significantly associated with the risk of EC (OR = 11.02, 95% CI = 7.51-16.16, P < 0.05). In the meantime, MMP-9 overexpression was significantly associated with the tumor grade, FIGO stage, lymph node metastasis and myometrial invasion (Tumor grade: OR = 1.68, 95% CI = 1.09-2.58, P < 0.05; FIGO stage: OR = 3.25, 95% CI = 1.73-6.08, P < 0.05; Lymph node metastasis: OR = 2.98, 95% CI = 1.27-7.03, P < 0.05; Myometrial invasion: OR = 2.42, 95% CI = 1.42-4.12, P < 0.05) in Asians. In addition, the overall results showed that MMP-9 overexpression predicted a worse prognosis of EC (OR = 1.82, 95% CI = 1.01-2.62, P < 0.05).

Conclusions

MMP-9 overexpression might be a potential predictor of poor clinical progression and prognosis of EC.