bluuebunny/crossref_metadata_2025 huggingface dataset:
Short-Term and Long-Term Outcomes of Fetal Ventriculomegaly beyond Gestational 37 Weeks: A Retrospective Cohort Study
Authors: Chen Huiling , Bai Peng , Yang Shuqi , Jia Mingzhu , Tian Huan , Zou Juan , Xiao Xue
Published: January 2023

Birth defects have brought about major public health problems, and studying the clinical outcomes of the most common prenatal central nervous system abnormality, namely, fetal ventriculomegaly (VM), is helpful for improving reproductive health and fertility quality. This is a retrospective cohort study from 2011 to 2020 in the West China Second University Hospital, Sichuan University, aiming to evaluate the short-term and long-term outcomes of VM over 37 weeks’ gestation to exclude the influence of preterm birth. The study analyzed data from 401 term pregnancies, with 179 VM and 222 controls. From the short-term outcomes, the rate of the neonatal intensive care unit (NICU) admission under the VM group (10.06%) was comparatively higher than the control (0.45%), but Apgar scores between both groups at 1 min, 5 min and 10 min were not significantly different. From the long-term outcomes, there were more infants with abnormal neurodevelopment under the VM group than control (14.53% vs. 2.25%, p < 0.001). In addition, NICU admission (p = 0.006), peak width of lateral ventricles (p = 0.030) and postnatal cranial ultrasound suggestive with VM (p = 0.002) were related to infants’ long-term outcomes. NICU admission during the perinatal period was an independent risk factor for the adverse long-term outcomes (OR = 3.561, 95% CI 1.029–12.320, p = 0.045). In conclusion, VM impairs short-term and long-term outcomes of term infants. Short-term outcome, especially NICU admission, could predict their adverse long-term outcomes.
Inhaled Sedation with Volatile Anesthetics for Mechanically Ventilated Patients in Intensive Care Units: A Narrative Review
Authors: Yassen Khaled Ahmed , Jabaudon Matthieu , Alsultan Hussah Abdullah , Almousa Haya , Shahwar Dur I , Alhejji Fatimah Yousef , Aljaziri Zainab Yaseen
Published: January 2023

Inhaled sedation was recently approved in Europe as an alternative to intravenous sedative drugs for intensive care unit (ICU) sedation. The aim of this narrative review was to summarize the available data from the literature published between 2005 and 2023 in terms of the efficacy, safety, and potential clinical benefits of inhaled sedation for ICU mechanically ventilated patients. The results indicated that inhaled sedation reduces the time to extubation and weaning from mechanical ventilation and reduces opioid and muscle relaxant consumption, thereby possibly enhancing recovery. Several researchers have reported its potential cardio-protective, anti-inflammatory or bronchodilator properties, alongside its minimal metabolism by the liver and kidney. The reflection devices used with inhaled sedation may increase the instrumental dead space volume and could lead to hypercapnia if the ventilator settings are not optimal and the end tidal carbon dioxide is not monitored. The risk of air pollution can be prevented by the adequate scavenging of the expired gases. Minimizing atmospheric pollution can be achieved through the judicious use of the inhalation sedation for selected groups of ICU patients, where the benefits are maximized compared to intravenous sedation. Very rarely, inhaled sedation can induce malignant hyperthermia, which prompts urgent diagnosis and treatment by the ICU staff. Overall, there is growing evidence to support the benefits of inhaled sedation as an alternative for intravenous sedation in ICU mechanically ventilated patients. The indication and management of any side effects should be clearly set and protocolized by each ICU. More randomized controlled trials (RCTs) are still required to investigate whether inhaled sedation should be prioritized over the current practice of intravenous sedation.
Toxin Induced Parkinsonism and Hospitalization Related Adverse Outcome Mitigation for Parkinson’s Disease: A Comprehensive Review
Authors: Dalton Kenneth R. , Kidd Charles J. , Hack Nawaz
Published: January 2023

Patients with Parkinson’s disease admitted to the hospital have unique presentations. This unique subset of patients requires a multidisciplinary approach with a knowledge-based care team that can demonstrate awareness of complications specific to Parkinson’s disease to reduce critical care admissions, morbidity, and mortality. Early recognition of toxic exposures, medication withdrawals, or medication-induced symptoms can reduce morbidity and mortality. This review can assist in the critical assessment of new or exacerbating Parkinson’s disease symptoms.
Clinical and Imaging Phenotypes and Outcomes in a Costa Rican Cohort of Acute Ischemic Stroke Survivors: A Retrospective Study
Authors: Serrano-Castro María Lorena , Garro-Zúñiga Mónica , Simon Erik , Tamayo Arturo , Siepmann Timo
Published: January 2023

Background: We characterized clinical and imaging phenotypes and their association with clinical outcomes in acute ischemic stroke (AIS) survivors in the understudied region of Costa Rica. Methods: We conducted a retrospective cohort study in AIS patients treated at a tertiary stroke center in Costa Rica from 2011–2015. Participants underwent detailed phenotyping for cardiovascular risk factors and stroke etiology. We assessed the association of ischemic brain lesion features and clinical outcomes using the Oxfordshire Community Stroke Project (OCSP) classification. Results: We included 684 AIS survivors (60.2% males, aged 68.1 ± 13.6 years, mean ± SD). While the cardiovascular risk profiles and mortality rates of our patients were similar to populations in European and North American countries, only 20.2% of patients with atrial fibrillation (AF) received anticoagulation. On multivariable analysis, patients with total anterior circulation infarct (TACI) displayed an increased risk of complications (OR: 4.2; 95% CI: 2.2–7.8; p < 0.001), higher mortality (OR: 6.9; 95% CI: 2.9–16.1; p < 0.001) and lower chance of functional independence at discharge (OR: 8.9; 95% CI: 4.1–19; p < 0.001) compared to non-TACI. The comorbidity of bronchopneumonia increased the probability of death by 14.5 times. Conclusions: Our observations in a Costa Rican cohort of AIS survivors might help improve local measures for preventing and managing AIS.
Real-World Use of Alirocumab: Experience from a Large Healthcare Provider
Authors: Elis Avishay , Melzer Cohen Cheli , Chodick Gabriel
Published: January 2023

With the emerging use of anti-PCSK9 monoclonal antibodies for lowering low-density lipoprotein cholesterol (LDL-C) levels, real-world evidence (RWE) is needed to evaluate drug effectiveness. This study aimed to characterize new users of alirocumab and evaluate its effectiveness in achieving LDL-C target levels. Included were patients initiating treatment with alirocumab from 1 August 2016 to 1 May 2020, with blood lipids evaluations during baseline (180 days prior to therapy initiation) and after 120 (±60) days of follow-up. Patients with treatment intensification during the follow-up period were excluded. LDL-C change from baseline and reaching LDL-C target levels, according to 2019 ESC/EAS guidelines, were evaluated. Among 623 included patients, 50.2% were men, the mean age was 65 years (±9 y), 62% were classified as very-high risk, and 76% had statin intolerance. During the follow-up, 65% (n = 407) were treated only with alirocumab. In 90% the initiation dose was 75 mg, and 21% were up-titrated. Alirocumab was associated with a 31.7% reduction in LDL-C, with 20.5% of patients reaching target levels. In this RWE study, alirocumab was used primarily as a single agent for eligible patients. Suboptimal use and adherence to therapy may have led to a lower LDL-C reduction compared to previous RCTs and most reported real-world studies.
Repetitive Bleomycin-Based Electrochemotherapy Improves Antitumor Effectiveness in 3D Tumor Models of Conjunctival Melanoma
Authors: Heinzelmann Joana , Hecht Sabine , Vogt Alexander , Siebolts Udo , Kaatzsch Peter , Viestenz Arne
Published: January 2023

Background: Conjunctival melanoma (CM) is associated with a high rate of local recurrence and poor survival rate. Novel therapeutic options are needed to reduce recurrence rate. The objective of the study was to demonstrate the improved effectiveness of electrochemotherapy (ECT) on CM using repetitive application. Methods: Tumor spheroids of three CM cell lines (CRMM1, CRMM2, CM2005.1) were treated repetitively with ECT using the chemotherapeutic agent bleomycin on days 3, 5, and 7 of culture. Application of bleomycin alone and electroporation alone served as controls. The cytotoxic effect was analyzed on day 10 compared to untreated control using an independent t-test. The spheroid outgrowth rate was measured. Result: CM tumor spheroid size (median value: 78%, SD: 32%) and viability (median value: 11%, SD: 11%) were dramatically reduced after repetitive ECT treatment (p-value < 0.001). Decreased proliferation capacity (down to 8%) and an increase of apoptotic cells were observed. In most repetitive ECT-treated spheroids, no viable or proliferating cells were detected. Only 33–40% of repetitive ECT-treated spheroids exhibited single outgrowing cells with a delay of time up to 38 days. Conclusion: Repetitive ECT application effectively induces cytotoxic effects in CM spheroids by inducing apoptosis, inhibiting proliferation and decreasing the percentage of surviving tumor cells. Thus, repetitive ECT results in improved antitumor effectiveness in CM and could be an alternative therapy option.
Endovascular Treatment of Ruptured Blood Blister-like Aneurysms Using the LVIS EVO Stents
Authors: Kubiak Kinga , Poncyljusz Wojciech
Published: January 2023

Blood blister-like aneurysms (BBAs) are rare cerebrovascular lesions that face serious challenges in surgical as well as endovascular treatment. In this paper, we present our experience in treating BBAs using the LVIS EVO stents. A total of 10 patients (mean age of 56.1 years) with 13 BBAs, who were admitted to our university hospital between April 2020 and November 2021 with a subarachnoid hemorrhage (SAH) due to aneurysm rupture, were treated using the LVIS EVO stents. Treatment of the BBAs consisted of stent-assisted coiling in four patients and stenting in six patients. The aneurysms were located within ICA (84.6%), VA (7.7%), and MCA (7.7%). Placement of the LVIS EVO stents was successful in all patients. No technical complications were observed. One in-stent thrombotic event occurred during the procedure. MRA for one-year follow-up was performed in nine patients. One patient died (Hunt and Hess Grade IV). LVIS EVO stents may be a beneficial treatment option for BBAs, as they provide high occlusion rates. However, the long-term efficacy remains uncertain.
What Binarization Method Is the Best for Amplitude Inline Fresnel Holograms Synthesized for Divergent Beams Using the Direct Search with Random Trajectory Technique?
Authors: Ovchinnikov Andrey S. , Krasnov Vitaly V. , Cheremkhin Pavel A. , Rodin Vladislav G. , Savchenkova Ekaterina A. , Starikov Rostislav S. , Evtikhiev Nikolay N.
Published: January 2023

Fast reconstruction of holographic and diffractive optical elements (DOE) can be implemented by binary digital micromirror devices (DMD). Since micromirrors of the DMD have two positions, the synthesized DOEs must be binary. This work studies the possibility of improving the method of synthesis of amplitude binary inline Fresnel holograms in divergent beams. The method consists of the modified Gerchberg–Saxton algorithm, Otsu binarization and direct search with random trajectory technique. To achieve a better quality of reconstruction, various binarization methods were compared. We performed numerical and optical experiments using the DMD. Holograms of halftone image with size up to 1024 × 1024 pixels were synthesized. It was determined that local and several global threshold methods provide the best quality. Compared to the Otsu binarization used in the original method of the synthesis, the reconstruction quality (MSE and SSIM values) is improved by 46% and the diffraction efficiency is increased by 27%.
Trichoderma pubescens Elicit Induced Systemic Resistance in Tomato Challenged by Rhizoctonia solani
Authors: Behiry Said , Soliman Seham A. , Massoud Magdy A. , Abdelbary Moawad , Kordy Ahmed M. , Abdelkhalek Ahmed , Heflish Ahmed
Published: January 2023

Rhizoctonia solani causes severe diseases in many plant species, particularly root rot in tomato plants. For the first time, Trichoderma pubescens effectively controls R. solani in vitro and in vivo. R. solani strain R11 was identified using the ITS region (OP456527); meanwhile, T. pubescens strain Tp21 was characterized by the ITS region (OP456528) and two genes (tef-1 and rpb2). The antagonistic dual culture method revealed that T. pubescens had a high activity of 76.93% in vitro. A substantial increase in root length, plant height, shoot fresh and dry, and root fresh and dry weight was indicated after applying T. pubescens to tomato plants in vivo. Additionally, it significantly increased the chlorophyll content and total phenolic compounds. The treatment with T. pubescens exhibited a low disease index (DI, 16.00%) without significant differences with Uniform® fungicide at a concentration of 1 ppm (14.67%), while the R. solani-infected plants showed a DI of 78.67%. At 15 days after inoculation, promising increases in the relative expression levels of three defense-related genes (PAL, CHS, and HQT) were observed in all T. pubescens treated plants compared with the non-treated plants. Plants treated with T. pubescens alone showed the highest expression value, with relative transcriptional levels of PAL, CHS, and HQT that were 2.72-, 4.44-, and 3.72-fold higher in comparison with control plants, respectively. The two treatments of T. pubescens exhibited increasing antioxidant enzyme production (POX, SOD, PPO, and CAT), while high MDA and H2O2 levels were observed in the infected plants. The HPLC results of the leaf extract showed a fluctuation in polyphenolic compound content. T. pubescens application alone or for treating plant pathogen infection showed elevated phenolic acids such as chlorogenic and coumaric acids. Therefore, the ability of T. pubescens to inhibit the growth of R. solani, enhance the development of tomato plants, and induce systemic resistance supports the application of T. pubescens as a potential bioagent for managing root rot disease and productivity increase of crops.
Advances in the Application of the Non-Conventional Yeast Pichia kudriavzevii in Food and Biotechnology Industries
Authors: Chu Yunfei , Li Mengmeng , Jin Jiahui , Dong Xiameng , Xu Ke , Jin Libo , Qiao Yanming , Ji Hao
Published: January 2023

Pichia kudriavzevii is an emerging non-conventional yeast which has attracted increased attention for its application in food and biotechnology areas. It is widespread in various habitats and often occurs in the spontaneous fermentation process of traditional fermented foods and beverages. The contributions of P. kudriavzevii in degrading organic acid, releasing various hydrolase and flavor compounds, and displaying probiotic properties make it a promising starter culture in the food and feed industry. Moreover, its inherent characteristics, including high tolerance to extreme pH, high temperature, hyperosmotic stress and fermentation inhibitors, allow it the potential to address technical challenges in industrial applications. With the development of advanced genetic engineering tools and system biology techniques, P. kudriavzevii is becoming one of the most promising non-conventional yeasts. This paper systematically reviews the recent progress in the application of P. kudriavzevii to food fermentation, the feed industry, chemical biosynthesis, biocontrol and environmental engineering. In addition, safety issues and current challenges to its use are discussed.
Recent Advances in Search of Bioactive Secondary Metabolites from Fungi Triggered by Chemical Epigenetic Modifiers
Authors: Xue Mengyao , Hou Xuwen , Fu Jiajin , Zhang Jiayin , Wang Jiacheng , Zhao Zhitong , Xu Dan , Lai Daowan , Zhou Ligang
Published: January 2023

Genomic analysis has demonstrated that many fungi possess essential gene clusters for the production of previously unobserved secondary metabolites; however, these genes are normally reduced or silenced under most conditions. These cryptic biosynthetic gene clusters have become treasures of new bioactive secondary metabolites. The induction of these biosynthetic gene clusters under stress or special conditions can improve the titers of known compounds or the production of novel compounds. Among the inducing strategies, chemical-epigenetic regulation is considered a powerful approach, and it uses small-molecule epigenetic modifiers, which mainly act as the inhibitors of DNA methyltransferase, histone deacetylase, and histone acetyltransferase, to promote changes in the structure of DNA, histones, and proteasomes and to further activate cryptic biosynthetic gene clusters for the production of a wide variety of bioactive secondary metabolites. These epigenetic modifiers mainly include 5-azacytidine, suberoylanilide hydroxamic acid, suberoyl bishydroxamic acid, sodium butyrate, and nicotinamide. This review gives an overview on the method of chemical epigenetic modifiers to trigger silent or low-expressed biosynthetic pathways to yield bioactive natural products through external cues of fungi, mainly based on the research progress in the period from 2007 to 2022. The production of about 540 fungal secondary metabolites was found to be induced or enhanced by chemical epigenetic modifiers. Some of them exhibited significant biological activities such as cytotoxic, antimicrobial, anti-inflammatory, and antioxidant activity.
The Potential of Ectomycorrhizal Fungi to Modulate below and Aboveground Communities May Be Mediated by 1-Octen-3-ol
Authors: Ferreira Inês , Dias Teresa , Cruz Cristina
Published: January 2023

It is known that ectomycorrhizal (ECM) fungi can modulate below and aboveground communities. They are a key part of belowground communication as they produce a vast array of metabolites, including volatile organic compounds (VOCs) such as 1-octen-3-ol. Here, we tested if the VOC 1-octen-3-ol may be involved in the ECM fungal mechanisms that modulate below and aboveground communities. For that, we conducted three in vitro assays with ECM fungi and the 1-octen-3-ol volatile to (i) explore the effects of mycelium growth of three ECM species, (ii) investigate the impact on the germination of six host Cistaceae species, and (iii) study the impact on host plant traits. The effects of 1-octen-3-ol on mycelium growth of the three ECM species depended on the dose and species: Boletus reticulatus was the most sensitive species to the low (VOC) dose, while T. leptoderma was the most tolerant. In general, the presence of the ECM fungi resulted in higher seed germination, while 1-octen-3-ol resulted in lower seed germination. The combined application of the ECM fungus and the volatile further inhibited seed germination, possibly due to the accumulation of 1-octen-3-ol above the plant species’ threshold. Seed germination and plant development of Cistaceae species were influenced by ECM fungal volatiles, suggesting that 1-octen-3-ol may mediate changes in below and aboveground communities.
Re-Evaluating Botryosphaeriales: Ancestral State Reconstructions of Selected Characters and Evolution of Nutritional Modes
Authors: Rathnayaka Achala R. , Chethana K. W. Thilini , Phillips Alan J. L. , Liu Jian-Kui , Samarakoon Milan C. , Jones E. B. Gareth , Karunarathna Samantha C. , Zhao Chang-Lin
Published: January 2023

Botryosphaeriales (Dothideomycetes, Ascomycota) occur in a wide range of habitats as endophytes, saprobes, and pathogens. The order Botryosphaeriales has not been subjected to evaluation since 2019 by Phillips and co-authors using phylogenetic and evolutionary analyses. Subsequently, many studies introduced novel taxa into the order and revised several families separately. In addition, no ancestral character studies have been conducted for this order. Therefore, in this study, we re-evaluated the character evolution and taxonomic placements of Botryosphaeriales species based on ancestral character evolution, divergence time estimation, and phylogenetic relationships, including all the novel taxa that have been introduced so far. Maximum likelihood, maximum parsimony, and Bayesian inference analyses were conducted on a combined LSU and ITS sequence alignment. Ancestral state reconstruction was carried out for conidial colour, septation, and nutritional mode. Divergence times estimates revealed that Botryosphaeriales originated around 109 Mya in the early epoch of the Cretaceous period. All six families in Botryosphaeriales evolved in the late epoch of the Cretaceous period (66–100 Mya), during which Angiosperms also appeared, rapidly diversified and became dominant on land. Families of Botryosphaeriales diversified during the Paleogene and Neogene periods in the Cenozoic era. The order comprises the families Aplosporellaceae, Botryosphaeriaceae, Melanopsaceae, Phyllostictaceae, Planistromellaceae and Saccharataceae. Furthermore, current study assessed two hypotheses; the first one being “All Botryosphaeriales species originated as endophytes and then switched into saprobes when their hosts died or into pathogens when their hosts were under stress”; the second hypothesis states that “There is a link between the conidial colour and nutritional mode in botryosphaerialean taxa”. Ancestral state reconstruction and nutritional mode analyses revealed a pathogenic/saprobic nutritional mode as the ancestral character. However, we could not provide strong evidence for the first hypothesis mainly due to the significantly low number of studies reporting the endophytic botryosphaerialean taxa. Results also showed that hyaline and aseptate conidia were ancestral characters in Botryosphaeriales and supported the relationship between conidial pigmentation and the pathogenicity of Botryosphaeriales species.
Clinical, Imaging and Neurogenetic Features of Patients with Gliomatosis Cerebri Referred to a Tertiary Neuro-Oncology Centre
Authors: Doig David , Thorne Lewis , Rees Jeremy , Fersht Naomi , Kosmin Michael , Brandner Sebastian , Jäger Hans Rolf , Thust Stefanie
Published: January 2023

Introduction: Gliomatosis cerebri describes a rare growth pattern of diffusely infiltrating glioma. The treatment options are limited and clinical outcomes remain poor. To characterise this population of patients, we examined referrals to a specialist brain tumour centre. Methods: We analysed demographic data, presenting symptoms, imaging, histology and genetics, and survival in individuals referred to a multidisciplinary team meeting over a 10-year period. Results: In total, 29 patients fulfilled the inclusion criteria with a median age of 64 years. The most common presenting symptoms were neuropsychiatric (31%), seizure (24%) or headache (21%). Of 20 patients with molecular data, 15 had IDH wild-type glioblastoma, with an IDH1 mutation most common in the remainder (5/20). The median length of survival from MDT referral to death was 48 weeks (IQR 23 to 70 weeks). Contrast enhancement patterns varied between and within tumours. In eight patients who had DSC perfusion studies, five (63%) had a measurable region of increased tumour perfusion with rCBV values ranging from 2.8 to 5.7. A minority of patients underwent MR spectroscopy with 2/3 (66.6%) false-negative results. Conclusions: Gliomatosis imaging, histological and genetic findings are heterogeneous. Advanced imaging, including MR perfusion, could identify biopsy targets. Negative MR spectroscopy does not exclude the diagnosis of glioma.
D-Dimer beyond Diagnosis of Pulmonary Embolism: Its Implication for Long-Term Prognosis in Cardio-Oncology Era
Authors: Himeno Masafumi , Nagatomo Yuji , Miyauchi Akira , Sakamoto Aimi , Kiyose Keita , Yukino-Iwashita Midori , Kawai Akane , Naganuma Tsukasa , Maekawara Satonori , Naito Ayami , Kagami Kazuki , Yumita Yusuke , Yasuda Risako , Toya Takumi , Ikegami Yukinori , Masaki Nobuyuki , Adachi Takeshi
Published: January 2023

Venous thromboembolism (VTE) is a common comorbidity of cancer, often referred to as cancer-associated thrombosis (CAT). Even though its prevalence has been increasing, its clinical picture has not been thoroughly investigated. In this single-center retrospective observational study, 259 patients who were treated for pulmonary embolism (PE) between January 2015 and December 2020 were available for analysis. The patients were divided by the presence or absence of concomitant malignancy, and those with malignancy (N = 120, 46%) were further classified into active (N = 40, 15%) and inactive groups according to the treatment status of malignancy. In patients with malignancy, PE was more often diagnosed incidentally by computed tomography or D-dimer testing, and the proportion of massive PE was lower. Although D-dimer levels overall decreased after the initiation of anticoagulation therapy, concomitant malignancy was independently associated with higher D-dimer at discharge despite the lower severity of PE at onset. The patients with malignancy had a poor prognosis during post-discharge follow-up. Active malignancy was independently associated with major adverse cardiovascular events (MACE) and major bleeding. D-dimer at discharge was an independent predictor of mortality even after adjustment for malignancy. This study’s findings suggest that CAT-PE patients might have hypercoagulable states, which can potentially lead to a poorer prognosis.
Altered White Matter Network Topology in Panic Disorder
Authors: Jiang Molin , Zhang Ping , Yang Xiangyun , Yu Aihong , Zhang Jie , Xu Xiaoyu , Li Zhanjiang
Published: January 2023

Panic disorder (PD) is an anxiety disorder that impairs life quality and social function and is associated with distributed brain regions. However, the alteration of the structural network remains unclear in PD patients. This study explored the specific characteristics of the structural brain network in patients with PD by graph theory analysis of diffusion tensor images (DTI). A total of 81 PD patients and 48 matched healthy controls were recruited for this study. The structural networks were constructed, and the network topological properties for individuals were estimated. At the global level, the network efficiency was higher, while the shortest path length and clustering coefficient were lower in the PD group compared to the healthy control (HC) group. At the nodal level, the PD group showed a widespread higher nodal efficiency and lower average shortest path length in the prefrontal, sensorimotor, limbic, insula, and cerebellum regions. Overall, the current results showed that the alteration of information processing in the fear network might play a role in the pathophysiology of PD.
Clinical Outcomes of Stereotactic Body Radiotherapy (SBRT) for Oligometastatic Patients with Lymph Node Metastases from Gynecological Cancers
Authors: Facondo Giuseppe , Vullo Gianluca , De Sanctis Vitaliana , Rotondi Margherita , Sigillo Riccardo Carlo , Valeriani Maurizio , Osti Mattia Falchetto
Published: January 2023

Background: To evaluate clinical outcomes of stereotactic body radiation therapy (SBRT) as a local treatment for lymph node metastases from gynecological cancers. Methods: Between November 2007 and October 2021, we retrospectively analyzed 29 lymph node metastases in 22 oligometastatic/oligoprogressive patients treated with SBRT. The Kaplan–Meier method was used to estimate the rates survival. Univariate analysis for prognostic factors were performed with the log-rank test, and Cox proportional hazards regression was used to estimate hazard ratios (HR). Results: Median age was 62 years (IQR, 50–80 years). Median follow-up was 17 months (IQR 10.5–31 months). The median survival was 22 months (CI 95%: 4.2–39.7, IQR: 12.5–34.5 months). Six months, one year and two year overall survival (OS) were 96.6%, 85.2%, and 48.7%, respectively. Median local control (LC) was not reached. Six months, 1one year and 2 year were 93.1%, 87.9%, and 79.9%, respectively. Distant metastasis free survival (DMFS) at one year, and two year was 53% and 37.1%, respectively Four patients (18%) experienced acute G1–G2 toxicities. No G3–4 acute toxicity was reported, and no late toxicity was observed. Conclusions: SBRT for lymph node recurrence offers excellent in-field tumor control with safe profile and low toxicities. Size, number of oligometastases, and time primary tumor to RT seem to be significant prognostic factors.
Ovarian Morphometric and Histologic Characteristics and Correlation with Clinical Factors: A Cross-Sectional Study
Authors: Giovannopoulou Eirini , Karakasi Maria-Valeria , Kouroupi Maria , Ieronimaki Argyro-Ioanna , Papakonstantinou Eleni , Giatromanolaki Alexandra , Tsikouras Panagiotis , Pavlidis Pavlos
Published: January 2023

Reproductive lifespan is determined by the reserve of ovarian follicles; their quality and quality determine the fertility potential at a given point in time for a particular individual. Inter-individual variations related to morphometry, laterality, medical history, demographic characteristics and ethnicity may impact ovarian histology, which however, has not been extensively studied or documented. The present cross-sectional study aims to investigate the potential association of clinical factors (age, medical and obstetric history) with ovarian morphometry and histology in females of reproductive age in the local population. The sample included 31 specimens of whole human ovaries, obtained from surgical/autopsy procedures in reproductive-aged women, processed at the Pathology Department. Morphometric characteristics were assessed, including shape, color, length, width, thickness and gross ovarian pathology. Random samples of specific dimensions were histologically examined to determine follicular counts. The results were analyzed statistically in correlation to morphometric characteristics and medical history. The majority of the patients had oval-shaped ovaries (77.8% right; 92.3% left; p = 0.368) of whitish color (38.9% right; 46.2% left; p > 0.999). Right ovaries had significantly greater length, width and volume (p-values 0.018, 0.040 and 0.050, respectively). Thickness was equivalent, as well as follicular distribution of all classes. Age correlated inversely with ovarian volume and primordial/primary follicular count on histology. Women with a caesarian-section history yielded significantly lower primordial/primary follicular counts. As estimated by ovarian histology, macroscopic and clinical factors may be significantly associated with actual ovarian reserve.
Large Prostate Volume Does Not Negatively Impact Health-Related Quality of Life in Patients with Prostate Cancer Treated with Ultrahypofractionated Stereotactic Body Radiotherapy
Authors: Milecki Piotr , Adamska Anna , Rucinska Anna , Pałucki Grzegorz , Szumiło Agnieszka , Skrobała Agnieszka , Jodda Agata , Michalak Michał
Published: January 2023

Background: Survival outcomes after primary radiotherapy for localized prostate cancer (PCa) are excellent, regardless of the specific treatment modality. For this reason, health-related quality of life (HRQOL) has come to play an ever more important role in treatment selection. Stereotactic body radiation therapy (SBRT) is increasingly used to treat patients with PCa. However, the impact of prostate volume on HRQOL is not clear. In this study, we aimed to determine whether a large prostate volume negatively influences HRQOL outcomes in patients undergoing ultrahypofractionated SBRT. Material and Methods: We conducted a prospective study of 530 men with low- and intermediate-risk localized PCa. All patients were treated from 2013 to 2017 with SBRT (Cyberknife system). HRQOL data were collected at baseline (pre-treatment), immediately after treatment, and at 12 and 24 months. QOL variables were assessed with the European Organization for Research and Treatment of Cancer QLQ-C30 and PR-25 module. Differences in the QLQ-C30 scales were considered clinically relevant when the change was >10 points. For the analysis, patients were classified into two groups according to prostate volume (≤60 vs. >60 cm3). Results: The prostate volume was ≤60 cm3 in 415 patients (78.3%) and >60 cm3 in 115 (21.7%). No between-group differences were observed at baseline for any of the following variables: clinical stage; hormonal therapy; marital status; educational level; or employment status. No clinically-significant deterioration (functional and symptom scales) was observed in either group between the baseline and 24-month assessment. There were no clinically-relevant differences between the groups on any of the HRQOL variables, regardless of the prostate volume. Conclusions: This study shows that a large prostate volume (>60 cm3) does not appear to negatively impact HRQOL outcomes at two years in patients with localized prostate cancer treated with ultrahypofractionated SBRT administered with the CyberKnife system.
Measuring Nasal Patency and the Sense of Smell in CRSwNP Patients Treated with Dupilumab
Authors: Ottaviano Giancarlo , De Corso Eugenio , Cantone Elena , Ciofalo Andrea , Saccardo Tommaso , Bernardi Riccardo , Mairani Edoardo , Montuori Claudio , Roccuzzo Giuseppe , Soldati Livia , Randon Benedetto , Zampollo Sonny , Chicco Alessandra Di , Visconti Francesca , Scarpa Bruno , Nicolai Piero
Published: January 2023

Chronic rhinosinusitis with nasal polyps (CRSwNP) in the most severe forms is associated with a poor quality of life. Dupilumab has been suggested as an add-on treatment option for severe CRSwNP. Severe CRSwNP patients treated with dupilumab in different rhinological units were followed up at 1, 3, 6 and 12 months from the first administration and were considered for this study. At baseline (T0) and at each follow-up, patients underwent nasal endoscopy and completed the sinonasal outcome test (SNOT)-22, a visual analogue scale (VAS) for smell/nasal obstruction, peak nasal inspiratory flow (PNIF) and the Sniffin’ Sticks identification test (SSIT). The aim of the present study was to evaluate the effects of dupilumab in patients with severe uncontrolled CRSwNP on recovering nasal obstruction and smell impairment. Moreover, the method between PNIF and SSIT with the highest correlation with patients’ response to dupilumab was evaluated. One hundred forty-seven patients were included. All parameters improved during treatment (p < 0.001). At T0, no correlations were found between PNIF and nasal symptoms. Nevertheless, during the following evaluations significant correlations between PNIF changes and both nasal symptoms and NPS were observed (p < 0.05). At T0, SSIT did not correlate with SNOT-22. Similarly to PNIF, during the follow-up SSIT changes significantly correlated with nasal symptom and NPS (p < 0.05). Comparing PNIF and SSIT correlations with SNOT-22 and NPS, PNIF showed a higher correlation with both. Dupilumab improves nasal obstruction and the sense of smell. PNIF and SSIT are effective tools in monitoring patients’ response to dupilumab.
Comprehensive Analysis of Necroptosis Landscape in Skin Cutaneous Melanoma for Appealing its Implications in Prognosis Estimation and Microenvironment Status
Authors: Cao Xiaoying , He Jiaming , Chen An , Ran Jianhua , Li Jing , Chen Dilong , Zhang Hengshu
Published: January 2023

Purpose: Due to poor prognosis and immunotherapy failure of skin cutaneous melanoma (SKCM), this study sought to find necroptosis-related biomarkers to predict prognosis and improve the situation with predicted immunotherapy drugs. Experimental Design: The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression Program (GTEx) database were utilized to recognize the differential necroptosis-related genes (NRGs). Univariate Cox (uni-Cox) and least absolute shrinkage and selection operator (LASSO) Cox analysis were utilized for prognostic signature establishment. The signature was verified in the internal cohort. To assess the signature’s prediction performance, the area under the curve (AUC) of receiver operating characteristic (ROC) curves, Kaplan-Meier (K-M) analyses, multivariate Cox (multi-Cox) regression, nomogram, and calibration curves were performed. The molecular and immunological aspects were also reviewed using single-sample gene set enrichment analysis (ssGSEA). Cluster analysis was performed to identify the different types of SKCM. Finally, the expression of the signature gene was verified by immunohistochemical staining. Results: On basis of the 67 NRGs, 4 necroptosis-related genes (FASLG, PLK1, EGFR, and TNFRSF21) were constructed to predict SKCM prognosis. The area’s 1-, 3-, and 5-year OS under the AUC curve was 0.673, 0.649, and 0.677, respectively. High-risk individuals had significantly lower overall survival (OS) compared to low-risk patients. Immunological status and tumor cell infiltration in high-risk groups were significantly lower, indicating an immune system that was suppressed. In addition, hot and cold tumors could be obtained by cluster analysis, which is helpful for accurate treatment. Cluster 1 was considered a hot tumor and more susceptible to immunotherapy. Immunohistochemical results were consistent with positive and negative regulation of coefficients in signature. Conclusion: The results of this finding supported that NRGs could predict prognosis and help make a distinction between the cold and hot tumors for improving personalized therapy for SKCM.
Love Addiction, Adult Attachment Patterns and Self-Esteem: Testing for Mediation Using Path Analysis
Authors: Gori Alessio , Russo Sara , Topino Eleonora
Published: January 2023

Love addiction is a dysfunctional relational modality that takes on the addiction characteristics and which, for the individuals who suffer from it, can have a negative and pervasive impact on various areas of functioning. The objective of this research was the analysis the factors that can be associated with love addiction, particularly focusing on adult attachment patterns and self-esteem. A sample group of 300 individuals who declared themselves to have a romantic relationship was involved in this research (Mage = 37.83 years, SD = 12.937). They completed an online survey including the Love Addiction Inventory—Short form, Relationship Questionnaire, and Rosenberg Self-Esteem Scale. Results showed significant and positive associations between preoccupied and fearful adult attachment and love addiction. Furthermore, these relationships were totally mediated by self-esteem. Gender and age were controlled as potential covariates and showed significant effects in influencing the levels of self-esteem and love addiction. Such findings may provide useful information for orienting future research and supporting an effective clinical practice.
Fusing Multiview Functional Brain Networks by Joint Embedding for Brain Disease Identification
Authors: Wang Chengcheng , Zhang Limei , Zhang Jinshan , Qiao Lishan , Liu Mingxia
Published: January 2023

Background: Functional brain networks (FBNs) derived from resting-state functional MRI (rs-fMRI) have shown great potential in identifying brain disorders, such as autistic spectrum disorder (ASD). Therefore, many FBN estimation methods have been proposed in recent years. Most existing methods only model the functional connections between brain regions of interest (ROIs) from a single view (e.g., by estimating FBNs through a specific strategy), failing to capture the complex interactions among ROIs in the brain. Methods: To address this problem, we propose fusion of multiview FBNs through joint embedding, which can make full use of the common information of multiview FBNs estimated by different strategies. More specifically, we first stack the adjacency matrices of FBNs estimated by different methods into a tensor and use tensor factorization to learn the joint embedding (i.e., a common factor of all FBNs) for each ROI. Then, we use Pearson’s correlation to calculate the connections between each embedded ROI in order to reconstruct a new FBN. Results: Experimental results obtained on the public ABIDE dataset with rs-fMRI data reveal that our method is superior to several state-of-the-art methods in automated ASD diagnosis. Moreover, by exploring FBN “features” that contributed most to ASD identification, we discovered potential biomarkers for ASD diagnosis. The proposed framework achieves an accuracy of 74.46%, which is generally better than the compared individual FBN methods. In addition, our method achieves the best performance compared to other multinetwork methods, i.e., an accuracy improvement of at least 2.72%. Conclusions: We present a multiview FBN fusion strategy through joint embedding for fMRI-based ASD identification. The proposed fusion method has an elegant theoretical explanation from the perspective of eigenvector centrality.
The Rationale for Vitamin, Mineral, and Cofactor Treatment in the Precision Medical Care of Autism Spectrum Disorder
Authors: Indika Neluwa-Liyanage R. , Frye Richard E. , Rossignol Daniel A. , Owens Susan C. , Senarathne Udara D. , Grabrucker Andreas M. , Perera Rasika , Engelen Marielle P. K. J. , Deutz Nicolaas E. P.
Published: January 2023

Children with autism spectrum disorder may exhibit nutritional deficiencies due to reduced intake, genetic variants, autoantibodies interfering with vitamin transport, and the accumulation of toxic compounds that consume vitamins. Importantly, vitamins and metal ions are essential for several metabolic pathways and for neurotransmitter functioning. The therapeutic benefits of supplementing vitamins, minerals (Zinc, Magnesium, Molybdenum, and Selenium), and other cofactors (coenzyme Q10, alpha-lipoic acid, and tetrahydrobiopterin) are mediated through their cofactor as well as non-cofactor functions. Interestingly, some vitamins can be safely administered at levels far above the dose typically used to correct the deficiency and exert effects beyond their functional role as enzyme cofactors. Moreover, the interrelationships between these nutrients can be leveraged to obtain synergistic effects using combinations. The present review discusses the current evidence for using vitamins, minerals, and cofactors in autism spectrum disorder, the rationale behind their use, and the prospects for future use.
Association of CT-Derived Extracardiac Features and Aortic Annulus Size in Patients Planned for TAVI
Authors: Volodarsky Igor , Perhulov Vladimir , Gochman Galyna , Cuciuc Valeriu , Welt Michael , Gandelman Gera , George Jacob
Published: January 2023

Introduction: Transcatheter aortic valve implantation (TAVI) is commonly used to treat patients with stenosed aortic valves. CT is one of the crucial steps in planning TAVI to obtain measurements of the aortic annulus to choose an appropriately sized prosthesis. Incorrect measurements can lead to patient-prosthesis mismatch and other complications. However, some patients cannot undergo ECG-gated CT with radiocontrast because of the presence of radiopaque objects in the thorax, arrhythmia, renal failure, etc. Aim: To explore supplementary methods to improve aortic annulus sizing for TAVI by extracardiac measurements. Methods: We included all patients who underwent CT as part of TAVI planning. Measurements of femoral and iliac arteries and the femoral head cross-sectional area were performed. Results: CT scans of 139 patients were included in this study. Sixty-three patients (45%) were males. Mean age of the female patients was 79.6 ± 7.1 years and of the male patients was 81.3 ± 6.1 years. Mean aortic annulus perimeter among female patients was 74.3 ± 6 mm (range 61.9–88.2) and 83 ± 7.9 mm among male patients (range 70.1–74.3 mm). Mean diameters of common iliac, external iliac, and common femoral arteries were 9.2 ± 1.8, 7.6 ± 1, 7.6 ± 1 mm, respectively, for females and 10.2 ± 1.8, 8.5 ± 1.3, and 8.6 ± 1.4 mm for males. Mean perimeter of the femoral head (average value of right and left femoral heads) among the female patients was 137.8 ± 6.3 mm, and among male patients was 155 ± 9.6 mm. A significant correlation was observed between the perimeter of the aortic annulus and the perimeter of the femoral head (Pearson’s R2 = 0.224). The correlation between the aortic annulus perimeter and the femoral head perimeter was stronger among men than among women (Pearson’s R2 = 0.66 and 0.19, respectively). Conclusion: Femoral head diameter is associated with annulus size. This may help size the appropriate prosthesis in cases where the measurements by CT are in the border zone if corroborated by clinically driven data.
Effectiveness of Hyperthermic Intraperitoneal Chemotherapy Associated with Cytoreductive Surgery in the Treatment of Advanced Ovarian Cancer: Systematic Review and Meta-Analysis
Authors: Llueca Maria , Ibañez Maria Victoria , Climent Maria Teresa , Serra Anna , Llueca Antoni
Published: January 2023

Objective: The use of hyperthermic intraperitoneal chemotherapy (HIPEC) as a treatment for epithelial ovarian cancer remains controversial. Our study aims to analyze the overall survival and disease-free survival for the use of HIPEC as a treatment for advanced epithelial ovarian cancer after neoadjuvant chemotherapy. Methods: A systematic review and meta-analysis was carried out using PubMed, Cochrane, Web of Science, and ClinicalTrials.gov. A total of six studies were used, comprising a total of 674 patients. Results: The results of our meta-analysis of all studies analyzed together (observational and randomized controlled trials (RCT)) did not achieve significant results. Contrary to the OS (HR = 0.56, 95% IC = 0.33–0.95, p = 0.03) and DFS (HR = 0.61, 95% IC = 0.43–0.86, p < 0.01) of the RCT analyzed separately, a clear impact on survival was suggested. The subgroup analysis showed that studies making use of higher temperatures (≥42 °C) for a shorter period of time (≤60 min) achieved better results for both OS and DFS, as well as the use of cisplatin as the form of chemotherapy in HIPEC. Moreover, the use of HIPEC did not increase high-grade complications. Conclusions: The addition of HIPEC to cytoreductive surgery demonstrates an improvement in OS and DFS for patients with epithelial ovarian cancer in advanced stages, without an increase in the number of complications. The use of cisplatin as chemotherapy in HIPEC obtained better results.
Etiological Diagnosis and Personalized Therapy for Hypertension: A Hypothesis of the REASOH Classification
Authors: Xu Chong , Li Moran , Meng Weilun , Han Jun , Zhao Song , Tang Jiamin , Yang Haotian , Maimaitiaili Rusitanmujiang , Teliewubai Jiadela , Yu Shikai , Chi Chen , Fan Ximin , Xiong Jing , Zhao Yifan , Xu Yawei , Zhang Yi
Published: January 2023

With the epidemic of risk factors such as unhealthy lifestyle, obesity and mental stress, the prevalence of hypertension continues to rise across the world. Although standardized treatment protocols simplify the selection of antihypertensive drugs and ensure therapeutic efficacy, the pathophysiological state of some patients remains, which may also lead to the development of other cardiovascular diseases. Thus, there is an urgent need to consider the pathogenesis and selection of antihypertensive drug for different type of hypertensive patients in the era of precision medicine. We proposed the REASOH classification, based on the etiology of hypertension, including renin-dependent hypertension, elderly-arteriosclerosis-based hypertension, sympathetic-active hypertension, secondary hypertension, salt-sensitive hypertension and hyperhomocysteinemia hypertension. The aim of this paper is to propose a hypothesis and provide a brief reference for the personalized treatment of hypertensive patients.