bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of necroptosis subtypes and development of necroptosis-related risk score model for in ovarian cancer
Authors: Ji Chen , He Yue , Wang Yan
Published: December 2022

Background: ith the ongoing development of targeted therapy, non-apoptotic cell death, including necroptosis, has become a popular topic in the field of prevention and treatment. The purpose of this study was to explore the effect of necroptosis-related genes (NRGs) on the classification of ovarian cancer (OV) subtypes and to develop a necroptosis-related risk score (NRRS) classification system.

Methods: 74 NRGs were obtained from the published studies, and univariate COX regression analysis was carried out between them and OV survival. Consensus clustering analysis was performed on OV samples according to the expression of NRGs related to prognosis. Furthermore, the NRRS model was developed by combining Weighted Gene Co-Expression Network Analysis (WGCNA) with least absolute shrinkage and selection operator (Lasso)-penalized Cox regression and multivariate Cox regression analysis. And the decision tree model was constructed based on the principle of random forest screening factors principle.

Results: According to the post-related NRGs, OV was divided into two necroptosis subtypes. Compared with Cluster 1 (C1), the overall survival (OS) of Cluster 2 (C2) was significantly shorter, stromal score and immune score, the infiltration level of tumor associated immune cells and the expression of 20 immune checkpoints were significantly higher. WGCNA identified the blue module most related to necroptosis subtype, and 12 genes in the module were used to construct NRRS. NRRS was an independent prognostic variable of OV. The OS of samples with lower NRRS was significantly longer, and tumor mutation burden and homologous recombination defect were more obvious.

Conclusion: This study showed that necroptosis plays an important role in the classification, prognosis, immune infiltration and biological characteristics of OV subtypes. The evaluation of tumor necroptosis may provide a new perspective for OV treatment.
Recent advances in understanding adverse effects associated with drugs targeting the serotonin receptor, 5-HT GPCR
Authors: Jamu Isabella Marie , Okamoto Haruko
Published: December 2022

It has been acknowledged that more women suffer from adverse effects of drugs than men globally. A group of drugs targeting serotonin [5-hydroxytryptamine] (5-HT) binding G-protein-coupled receptors (GPCRs) have been reported to preferentially affect women more than men, causing adverse effects such as breast cancer and infertility. 5-HT GPCR-targeted drugs in the central nervous system (CNS) manage psychiatric conditions, such as depression or bipolar and in the peripheral nervous system (PNS) treat migraines. Physiological characteristics such as specific types of hormones, higher body fat density and smaller body mass in women result in disparities in pharmacodynamics of drugs, thus explaining sex-related differences in the observed adverse effects. In this review, we discuss the side effects of drugs targeting 5-HT GPCRs based on serotonin's roles in the CNS and PNS. We have systematically reviewed adverse effects of drugs targeting 5-HT GPCR using information from the Food and Drug Administration and European Medicines Agency. Further information on drug side effects and receptor targets was acquired from the SIDER and DrugBank databases, respectively. These drugs bind to 5-HT GPCRs in the CNS, namely the brain, and PNS such as breasts, ovaries and testes, potentially causing side effects within these areas. Oestrogen affects both the biosynthesis of 5-HT and the densities of 5-HT GPCRs in given tissues and cells. 5-HT GPCR-targeting drugs perturb this process. This is likely a reason why women are experiencing more adverse effects than men due to their periodic increase and the relatively high concentrations of oestrogen in women and, thus a greater incidence of the oestrogen-mediated 5-HT system interference. In addition, women have a lower concentration of serotonin relative to men and also have a relatively faster rate of serotonin metabolism which might be contributing to the former. We discuss potential approaches that could mitigate at least some of the adverse effects experienced by women taking the 5-HT GPCR-targeting drugs.
Impact of Kawasaki disease on juvenile idiopathic arthritis in real-world patients: A population-based cohort study
Authors: Liao Li-Chin , Fu Yi-Hsiu , Chuang Chieh-Mao , Liao Pei-Lun , Wei James Cheng-Chung , Fu Yun-Ching
Published: December 2022

Objectives

Recent research has demonstrated the commonality of several biological markers between Kawasaki disease (KD) and juvenile idiopathic arthritis (JIA), including interleukin-1β and -6. Therefore, in this cohort study, we assessed whether KD increases the risk of JIA.

Methods

This study enrolled 7009 patients with and 56 072 individuals without KD in the period 2010–2018 from Taiwan’s National Health Insurance Research Database. On the basis of sex, age, and comorbidities, we executed propensity score matching at the ratio 1:8. The adjusted hazard ratio (aHR) for JIA was determined through multiple Cox regression. Stratified analysis and sensitivity tests were also employed.

Results

When adjusting for age, sex, and comorbidities, the JIA risk was noted to be 2.02-fold greater in children with KD than it was in those without (aHR: 2.02, 95% confidence interval: 1.12–3.67, p = 0.0205). The sensitivity test and subgroup analysis obtained consistent findings in the different sex and comorbidity subgroups.

Conclusion

Children’s risk of JIA is higher if they have KD. Pediatricians should consider the possibility of JIA in this population. More investigations are necessary to identify the pathological mechanisms that link JIA and KD.
Precision medicine: The use of tailored therapy in primary immunodeficiencies
Authors: Pinto Marta Valente , Neves João Farela
Published: December 2022

Primary immunodeficiencies (PID) are rare, complex diseases that can be characterised by a spectrum of phenotypes, from increased susceptibility to infections to autoimmunity, allergy, auto-inflammatory diseases and predisposition to malignancy. With the introduction of genetic testing in these patients and wider use of next-Generation sequencing techniques, a higher number of pathogenic genetic variants and conditions have been identified, allowing the development of new, targeted treatments in PID. The concept of precision medicine, that aims to tailor the medical interventions to each patient, allows to perform more precise diagnosis and more importantly the use of treatments directed to a specific defect, with the objective to cure or achieve long-term remission, minimising the number and type of side effects. This approach takes particular importance in PID, considering the nature of causative defects, disease severity, short- and long-term complications of disease but also of the available treatments, with impact in life-expectancy and quality of life. In this review we revisit how this approach can or is already being implemented in PID and provide a summary of the most relevant treatments applied to specific diseases.
Protective role of engineered extracellular vesicles loaded quercetin nanoparticles as anti-viral therapy against SARS-CoV-2 infection: A prospective review
Authors: Raghav Alok , Giri Richa , Agarwal Saurabh , Kala Sanjay , Jeong Goo-Bo-
Published: December 2022

Quercetin (QCT) is a naturally occurring phenolic flavonoid compound with inbuilt characteristics of antioxidant, anti-inflammatory, and immune protection. Several recent studies have shown that QCT and QCTits nanoparticles have therapeutic potential against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Novel therapeutics also include the implication of extracellular vesicles (EVs) to protect from SARS-CoV-2 viral infection. This article highlighted the therapeutic/prophylactic potential of engineered EVs loaded with QCT against SARS-CoV-2 infection. Several biotechnological engineering approaches are available to deliver EVs loaded with QCT nanoparticles. Among these biotechnological advances, a specific approach with significantly higher efficiency and yield has to be opted to fabricate such drug delivery of nano molecules, especially to combat SARS-CoV-2 infection. The current treatment regime protects the human body from virus infection but has some limitations including drugs and long-term steroid side effects. However, the vaccine strategy is somehow effective in inhibiting the spread of coronavirus disease-19 (COVID-19) infection. Moreover, the proposed exosomal therapy met the current need to repair the damaged tissue along with inhibition of COVID-19-associated complications at the tissue level. These scientific findings expand the possibilities and predictability of developing a novel and cost-effective therapeutic approach that combines the dual molecule, EVs and QCT nanoparticles, to treat SARS-CoV-2 infection. Therefore, the most suitable engineering method to fabricate such a drug delivery system should be better understood before developing novel therapeutics for clinical purposes.
Overnutrition-induced gout: An immune response to NLRP3 inflammasome dysregulation by XOD activity increased in quail
Authors: Wu Hao , Wang Yu , Ren Zhixin , Li Yaolei , Huang Jingjian , Lin Zhijian , Zhang Bing
Published: December 2022

Background

Gout is a progressive metabolic disease closely related to hyperuricemia and urate deposition, with an increasing prevalence and incidence across the globe. Recent studies have shown that the pathological process of gout includes two stages: asymptomatic hyperuricemia and MSU crystal deposition. However, the immune response during the development of hyperuricemia to gouty arthritis is not fully elucidated.

Methods

Thus, an overnutrition-induced whole-course gout model was established to clarify the immune response and pathological changes in the development from hyperuricemia to gouty arthritis. The quails without urate oxidase were used as experimental animals. And we confirmed that uric acid metabolic targets were changed when quails were in the asymptomatic hyperuricemia stage.

Results

When the quail showed gout symptoms, the NLRP3 inflammasome was activated, and the expressions of IL-1β, TNF-α, IL-6, IL-8, and IL-18 were significantly increased. The relationship between the uric acid metabolism target and the NLRP3 inflammasome may be the critical immune response between hyperuricemia and gouty arthritis. Our data showed that, in the process of gout disease, the expression of xanthine oxidase (XOD) has been increasing, which increases the level of uric acid, disrupts the balance of oxidative stress, generates a large amount of ROS, activates the NLRP3 inflammasome, and release IL-1β. Treatment with the XOD inhibitor can reduce uric acid, restore the body’s degree of peroxidative damage and antioxidant capacity, and inhibit NLRP3 inflammasome and IL-1β. In vitro, we extracted and identified primary fibroblast-like synoviocytes (FLS) from quail for the first time. Stimulating FLS with uric acid also caused ROS release and NLRP3 inflammasome activation. However, treatment with an XOD inhibitor prevented all these responses in FLS.

Conclusion

Our results indicate that the immune response between the uric acid metabolism target XOD and NLRP3 inflammasomes plays a crucial role in developing hyperuricemia to gouty arthritis, and inhibition of both XOD and NLRP3 inflammasomes may be an effective treatment for avoiding the development of asymptomatic hyperuricemia to MSU crystal deposition. Meanwhile, this study also provides an advantageous animal model for pathological mechanisms and research and development drugs for gout.
Safety and short-term outcomes of laparoscopic surgery for advanced gastric cancer after neoadjuvant immunotherapy: A retrospective cohort study
Authors: Su Jin , Guo Weihong , Chen Zhian , Wang Lingzhi , Liu Hao , Zhao Liying , Lin Tian , Li Fengping , Mao Xinyuan , Huang Huilin , Yu Jiang , Li Guoxin , Hu Yanfeng
Published: December 2022

Background

Immune checkpoint inhibitors (ICIs) have been increasingly used for the treatment of advanced gastric cancer (AGC). However, the safety and the short-term outcomes of laparoscopic gastrectomy for patients with AGC after neoadjuvant immunotherapy (NAI) remain unknown.

Methods

We retrospectively analyzed the patients with AGC who underwent laparoscopic surgery after neoadjuvant therapy between 1 January 2019 and 31 October 2021. We further compared the differences in postoperative complications, overall response rate, adverse events, surgical parameters, and postoperative recovery between two cohorts: the NAI group (NAI plus chemotherapy) and the neoadjuvant chemotherapy (NAC) group. Multivariable regression analyses were used to determine the risk factors for the overall response rate.

Results

Overall, 80 patients were enrolled, of whom 30 cases were included in the NAI cohort and 50 were included in the NAC cohort. The overall rate of postoperative complications was 30.0% in both groups (p = 1.000). The overall response rate was 70.0% in the NAI cohort and 40% in the NAC cohort (p = 0.012). The adverse effects were found in 16 cases (53.3%) of the NAI cohort and 23 cases (46.0%) of the NAC cohort (p = 0.645). There was no statistical difference in intraoperative bleeding (50 ml vs. 50 ml, p = 0.983), operation time (320.9 min vs. 303.5 min, p = 0.382), dissected lymph node count (43.5 vs. 40.0, p = 0.364), first postoperative anal aerofluxus (3 days vs. 3 days, p = 0.091), first liquid diet (4 days vs. 5 days, p = 0.213), and postoperative length of stay in the hospital (8 days vs. 7 days, p = 0.508) between the two groups. NAI was estimated to be the independent protective factor [odds ratio (OR) 4.931, 95% confidence interval (CI) (1.385–17.559), p = 0.014] for odds to overall response rate, whereas vessel invasion was found to be the significant risk factor [OR 0.113, 95% CI (0.027–0.475), p = 0.003].

Conclusions

Laparoscopic surgery after NAI combined with chemotherapy is a safe therapeutic choice for AGC and may bring better short-term outcomes due to a higher overall response rate.
Isolation, structures, bioactivities, application and future prospective for polysaccharides from Tremella aurantialba: A review
Authors: Yan Yonghuan , Wang Mengtian , Chen Ning , Wang Xu , Fu Chenghao , Li Yuemin , Gan Xiaoruo , Lv Pin , Zhang Yan
Published: December 2022

Since ancient times, Tremella aurantialba has been proposed to have medicinal and food benefits. Modern phytochemistry and pharmacological studies have demonstrated that polysaccharides, the main components from T. aurantialba appear to be an all-round talent resisting a variety of chronic inflammatory diseases and protecting against different types of tumors, diabetes and cardiovascular diseases. These health and pharmacological benefits have gained much attention from scholars around the world. Further, more and more methods for polysaccharides extraction, purification, structure identification have been proposed. Significantly, the bioactivity of fungus polysaccharides is affected by many factors such as extraction and purification conditions and chemical structure. This paper provides an overview of recent advances in the isolation, structural features and biological effects of polysaccharides derived from T. aurantialba, covers recent advances in the field and outlines future research and applications of these polysaccharides.
Dissimilatory nitrate reduction processes in surface sediments of shrimp ponds during the culture period
Authors: Sun Dongyao , Huang Jiafang , Luo Min , Chen Cheng , Lan Xue , Hu Weifang
Published: December 2022

Intensive aquaculture in estuaries and coasts has resulted in several ecological and environmental problems. Among various nitrogen transformation pathway, dissimilatory nitrate (NO3-) reduction is considered to be highly important in regulating reactive nitrogen. However, there are relatively few studies on the processes and contribution of NOx- reduction in sediment during the shrimp pond culture period. Three sediment NO3- reduction processes, denitrification (DNF), anaerobic ammonium oxidation (ANA), and dissimilatory NO3- reduction to ammonium (DNRA), were surveyed in eight shrimp ponds across three subtropical estuaries using 15N isotope tracing experiments. The rates of DNF, ANA and DNRA ranged from 2.87–18.11, 0.10–1.92, and 0.21–1.25 nmol N g -1 h -1, respectively. DNF was responsible for 64.2–91.6% of the total NO3- reduction. Regarding environmental factors, C and N substrates, as well as salinity, significantly affected NO3- reduction. In general, the N losses were approximately 32.43–131.64 g N m-2 yr-1 for DNF and 2.38–15.85 g N m-2 yr-1 for ANA in this study, indicating that coastal reclamation is a nonnegligible way to remove nitrogen. Our results provide a scientific foundation for understanding the mechanism of nitrogen cycling in the artificial aquatic environment of shrimp ponds.
Nitrogen cycling in sediments on the NW African margin inferred from N and O isotopes in benthic chambers
Authors: Dale Andrew W. , Clemens David , Dähnke Kirstin , Korth Frederike , Wankel Scott D. , Schroller-Lomnitz Ulrike , Wallmann Klaus , Sommer Stefan
Published: December 2022

Benthic nitrogen cycling in the Mauritanian upwelling region (NW Africa) was studied in June 2014 from the shelf to the upper slope where minimum bottom water O2 concentrations of 25 µM were recorded. Benthic incubation chambers were deployed at 9 stations to measure fluxes of O2, dissolved inorganic carbon (DIC) and nutrients (NO3-, NO2-, NH4+, PO43-, H4SiO4) along with the N and O isotopic composition of nitrate (δ15N-NO3- and δ18O-NO3-) and ammonium (δ15N-NH4+). O2 and DIC fluxes were similar to those measured during a previous campaign in 2011 whereas NH4+ and PO43- fluxes on the shelf were 2 – 3 times higher and possibly linked to a long-term decline in bottom water O2 concentrations. The mean isotopic fractionation of NO3- uptake on the margin, inferred from the loss of NO3- inside the chambers, was 1.5 ± 0.4 ‰ for 15/14N (15ϵapp) and 2.0 ± 0.5 ‰ for 18/16O (18ϵapp). The mean 18ϵapp:15ϵapp ratio on the shelf (< 100 m) was 2.1 ± 0.3, and higher than the value of 1 expected for microbial NO3-reduction. The 15ϵapp are similar to previously reported isotope effects for NO3- respiration in marine sediments but lower than determined in 2011 at a same site on the shelf. The sediments were also a source of 15N-enriched NH4+ (9.0 ± 0.7 ‰). A numerical model tuned to the benthic flux data and that specifically accounts for the efflux of 15N-enriched NH4+ from the seafloor, predicted a net benthic isotope effect of N loss (15ϵsed) of 3.6 ‰; far above the more widely considered value of ~0‰. This result is further evidence that the assumption of a universally low or negligible benthic N isotope effect is not applicable to oxygen-deficient settings. The model further suggests that 18ϵapp:15ϵapp trajectories > 1 in the benthic chambers are most likely due to aerobic ammonium oxidation and nitrite oxidation in surface sediments rather than anammox, in agreement with published observations in the water column of oxygen deficient regions.
Oleaster seed-derived activated carbon/ferrite nanocomposite for microwave absorption in the X-band range
Authors: Mahmoodi Mahsa , Aslibeiki Bagher , Peymanfar Reza , Naghshara Hamid
Published: December 2022

Conjugated carbonaceous structures achieved from biological materials were significantly considered electromagnetic wave absorbing materials due to their eye-catching dielectric, lightweight, low-cost, and chemical stability features. To strengthen the microwave absorbing performance of the porous carbon (Oleaster seeds), Fe3O4 magnetic nanoparticles have been successfully anchored onto the surface of biomass-derived material through a co-precipitation method. Noticeably, the dielectric constant, impedance matching, permeability, and microwave absorbing capability were improved by changing the carbon content. The optimized Fe3O4/activated carbon (AC) illustrated the excellent electromagnetic wave absorption performances with a maximum reflection loss (RL) value of −51.12 dB and an effective absorption bandwidth of ∼4 GHz (RL < 10 dB) with a thickness of 1 mm. The promoted microwave absorbing characteristics of Fe3O4/AC composites are rooted in improved impedance matching, eddy current loss, natural and exchange resonance, and specific surface area, bringing more polarization loss and multiple reflection and scattering. The presented research shed new light on the fabrication of practical microwave-absorbing materials based on biomass-derived materials with a facile experimental procedure.
A multicenter randomized phase 4 trial comparing sodium picosulphate plus magnesium citrate vs. polyethylene glycol plus ascorbic acid for bowel preparation before colonoscopy. The PRECOL trial
Authors: D’Angelo Valentina , Piccirillo Maria Carmela , Di Maio Massimo , Gallo Ciro , Bucci Cristina , Civiletti Corrado , Di Girolamo Elena , Marone Pietro , Rossi Giovanni Battista , Tempesta Alfonso Mario , Tracey Maura C. , Romano Marco , Miranda Agnese , Taranto Domenico , Sessa Gabriella , Esposito Pasquale , Salerno Raffaele , Pumpo Rossella , De Filippo Francesca Romana , Della Valle Elisabetta , de Bellis Mario , Perrone Francesco
Published: December 2022

Background

Adequate bowel preparation before colonoscopy is crucial. Unfortunately, 25% of colonoscopies have inadequate bowel cleansing. From a patient perspective, bowel preparation is the main obstacle to colonoscopy. Several low-volume bowel preparations have been formulated to provide more tolerable purgative solutions without loss of efficacy.

Objectives

Investigate efficacy, safety, and tolerability of Sodium Picosulphate plus Magnesium Citrate (SPMC) vs. Polyethylene Glycol plus Ascorbic Acid (PEG-ASC) solutions in patients undergoing diagnostic colonoscopy.

Materials and methods

In this phase 4, randomized, multicenter, two-arm trial, adult outpatients received either SPMC or PEG-ASC for bowel preparation before colonoscopy. The primary aims were quality of bowel cleansing (primary endpoint scored according to Boston Bowel Preparation Scale) and patient acceptance (measured with six visual analogue scales). The study was open for treatment assignment and blinded for primary endpoint assessment. This was done independently with videotaped colonoscopies reviewed by two endoscopists unaware of study arms. A sample size of 525 patients was calculated to recognize a difference of 10% in the proportion of successes between the arms with a two-sided alpha error of 0.05 and 90% statistical power.

Results

Overall 550 subjects (279 assigned to PEG-ASC and 271 assigned to SPMC) represented the analysis population. There was no statistically significant difference in success rate according to BBPS: 94.4% with PEG-ASC and 95.7% with SPMC (P = 0.49). Acceptance and willing to repeat colonoscopy were significantly better for SPMC with all the scales. Compliance was less than full in 6.6 and 9.9% of cases with PEG-ASC and SPMC, respectively (P = 0.17). Nausea and meteorism were significantly more bothersome with PEG-ASC than SPMC. There were no serious adverse events in either group.

Conclusion

SPMC and PEG-ASC are not different in terms of efficacy, but SPMC is better tolerated than PEG-ASC. SPMC could be an alternative to low-volume PEG based purgative solutions for bowel preparation.

Clinical trial registration

[ClinicalTrials.gov], Identifier [NCT01649674 and EudraCT 2011–000587–10].
Health horizons: Future trends and technologies from the European Medicines Agency’s horizon scanning collaborations
Authors: Vignali Valentina , Hines Philip A. , Cruz Ana Glória , Ziętek Barbara , Herold Ralf
Published: December 2022

In medicines development, the progress in science and technology is accelerating. Awareness of these developments and their associated challenges and opportunities is essential for medicines regulators and others to translate them into benefits for society. In this context, the European Medicines Agency uses horizon scanning to shine a light on early signals of relevant innovation and technological trends with impact on medicinal products. This article provides the results of systematic horizon scanning exercises conducted by the Agency, in collaboration with the World Health Organization (WHO) and the European Commission’s Joint Research Centre’s (DG JRC). These collaborative exercises aim to inform policy-makers of new trends and increase preparedness in responding to them. A subset of 25 technological trends, divided into three clusters were selected and reviewed from the perspective of medicines regulators. For each of these trends, the expected impact and challenges for their adoption are discussed, along with recommendations for developers, regulators and policy makers.
Case report: Later onset of NRAS-mutant metastatic melanoma in a patient with a partially-excised giant congenital melanocytic nevus
Authors: Costa Bruno Almeida , Zibara Victor , Singh Vasundhara , Hamid Omid , Gandhi Sonal , Moy Andrea P. , Betof Warner Allison S.
Published: December 2022

Despite recent advances in treatment and surveillance, metastatic melanoma still carries a poor prognosis. Large/giant congenital melanocytic nevi (CMNs) constitute a known risk factor for the condition, with the greatest risk for malignant transformation thought to be during childhood (median age at diagnosis of 3 years in a previous cohort). Herein, we present the case of a 30-year-old male who, after undergoing multiple excision/grafting procedures for a giant CMN as a child, was diagnosed with an NRAS-mutant, MDM2-amplified metastatic melanoma more than 20 years later. Response to ipilimumab/nivolumab immunotherapy, cisplatin/vinblastine/temozolomide chemotherapy, and nivolumab/relatlimab immunotherapy was poor. This case highlights the importance of lifetime monitoring with once-yearly dermatological examination (including lymph node palpation) in large/giant CMN patients, as well as the need for further clinical trials evaluating novel therapies for NRAS-mutant melanoma.
A comprehensive review on pathogenesis, associations, clinical findings, and treatment of livedoid vasculopathy
Authors: Seguí Mireia , Llamas-Velasco Mar
Published: December 2022

Livedoid vasculopathy (LV) is a thrombo-occlusive vasculopathy that involves the dermal vessels. Clinically, it is characterized by the presence of painful purpuric ulcers on the lower extremities. Histopathologically, it shows intraluminal fibrin deposition and thrombosis, segmental hyalinization, and endothelial proliferation. It is important to notice that the term “atrophie blanche” is descriptive and it includes not only patients with LV but also patients with a combination of vasculitis and vasculopathy, that is, LV and medium-sized vasculitis such as cutaneous polyarteritis nodosa (PANc). Diagnosis is based on a proper clinicopathological correlation, excluding the main differential diagnosis and considering vasculitis as a mimicker or concomitant diagnosis. Coagulation disorders must also be studied although they are not found in all LV. Its frequency is reviewed as well. Treatment of LV is challenging, and different therapies have been attempted. Among them, pain management, wound care, control of cardiovascular risk factors, and both antiplatelets and anticoagulants, mostly rivaroxaban, are the main therapies used. These different therapies as well as their degree of evidence are reviewed.
Spontaneous pregnancy after tracking ovulation during menstruation: A case report of a woman with premature ovarian insufficiency and repeated failure of in vitro fertilization
Authors: He Ye , Wang Wanlu , Wu Chunmei , Li Wenwen , Liu Hongjiang , Wei Zhaolian
Published: December 2022

The diagnosis of premature ovarian insufficiency (POI) is devastating in women of reproductive age because of the small chance of spontaneous pregnancy. Here, we report a very rare case with POI and repeated failure of in vitro fertilization (IVF) where the final result was natural fertilization following guidance to have sexual intercourse during menstruation as ovulation was monitored. Estradiol valerate was used to increase the thickness of the endometrium and stop the menstrual bleeding. There was a serum level of 208.44 IU/L of human chorionic gonadotropin (HCG) 14 days after the ovulation. Later, a series of transvaginal ultrasounds also indicated a normal-appearing intra-uterine pregnancy. A healthy baby girl was delivered at term by means of cesarean section. Our report suggested that although the chance of spontaneous pregnancy is relatively low in patients with POI with repeated IVF failures, as long as ovulation does occur, even if it happens during menstruation, natural pregnancy is still worth trying with a series of proper and personalized treatments.
Effects of whole maize high-grain diet feeding on colonic fermentation and bacterial community in weaned lambs
Authors: Cheng Chao , Yin Yuyang , Bian Gaorui
Published: December 2022

High-grain diet is commonly used in intensive production to boost yield in short term, which may cause adverse effects such as rumen and colonic acidosis in ruminants. Maize is one of the key components of high-grain diet, and different processing methods of maize affect the digestive absorption and gastrointestinal development of ruminants. To investigate the effects of maize form in high-grain diets on colonic fermentation and bacterial community of weaned lambs, twenty-two 2.5-month-old healthy Hu lambs were fed separately a maize meal low-grain diet (19.2% grain; CON), a maize meal high-grain diet (50.4% grain; CM), and a whole maize high-grain diet (50.4% grain; CG). After 7 weeks of feeding, the total volatile fatty acid concentration (P = 0.035) were significantly higher in lambs from CM than that from CON. The sequencing results of colonic content microbial composition revealed that the relative abundance of genera Parasutterella (P = 0.028), Comamonas (P = 0.031), Butyricicoccus (P = 0.049), and Olsenella (P = 0.010) were higher in CM than those in CON; compared with CM, the CG diet had the higher relative abundance of genera Bacteroides (P = 0.024) and Angelakisella (P = 0.020), while the lower relative abundance of genera Olsenella (P = 0.031) and Paraprevotella (P = 0.006). For colonic mucosal microbiota, the relative abundance of genera Duncaniella (P = 0.024), Succiniclasticum (P = 0.044), and Comamonas (P = 0.012) were significantly higher in CM than those in CON. In comparison, the relative abundance of genera Alistipes (P = 0.020) and Campylobacter (P = 0.017) were significantly lower. And the relative abundance of genera Colidextribacter (P = 0.005), Duncaniella (P = 0.032), Christensenella (P = 0.042), and Lawsonibacter (P = 0.018) were increased in the CG than those in the CM. Furthermore, the CG downregulated the relative abundance of genes encoding infectious-disease-parasitic (P = 0.049), cancer-specific-types (P = 0.049), and neurodegenerative-disease (P = 0.037) in colonic microbiota than those in the CM. Overall, these results indicated that maize with different grain sizes might influence the colonic health of weaned lambs by altering the composition of the colonic bacterial community.
Concurrent waterlogging and anthracnose-twister disease in rainy-season onions (Allium cepa): Impact and management
Authors: Salunkhe Vanita Navnath , Gedam Pranjali , Pradhan Aliza , Gaikwad Bhaskar , Kale Rajiv , Gawande Suresh
Published: December 2022

Waterlogging and anthracnose-twister disease are significant obstacles in rainy-season onion cultivation. As a shallow-rooted crop, onions are highly sensitive to waterlogging. Wherever rainy-season onion cultivation has been undertaken, the anthracnose-twister disease complex is also widespread across the world in addition to waterlogging. Waterlogging is the major predisposing factor for anthracnose and other fungal diseases. However, studies on the combined stress impact on onions have been ignored. In the present review, we have presented an overview of the anthracnose-twister disease, the waterlogging effect on host physiology, host-pathogen interaction under waterlogging stress, and appropriate management strategies to mitigate the combined stress effects. Crucial soil and crop management strategies can help cope with the negative impact of concurrent stresses. Raised bed planting with drip irrigation, the use of plant bio-regulators along with nutrient management, and need-based fungicide sprays would be the most reliable and feasible management options. The most comprehensive solution to withstand combined stress impacts would be a genetic improvement of commercial onion cultivars.
Natural inhibitors: A sustainable way to combat aflatoxins
Authors: Ahmad Malik M. , Qamar Firdaus , Saifi Monica , Abdin Malik Zainul
Published: December 2022

Among a few hundred mycotoxins, aflatoxins had always posed a major threat to the world. Apart from A. flavus, A. parasiticus, and A. nomius of Aspergillus genus, which are most toxin-producing strains, several fungal bodies including Fusarium, Penicillium, and Alternaria that can biosynthesis aflatoxins. Basically, there are four different types of aflatoxins (Aflatoxin B1 (AFB1), Aflatoxin B2 (AFB2), Aflatoxin G1 (AFG1), Aflatoxin G2 (AFG2)) are produced as secondary metabolites. There are certainly other types of aflatoxins found but they are the by-products of these toxins. The fungal agents generally infect the food crops during harvesting, storing, and/or transporting; making a heavy post-harvest as well as economic loss in both developed and developing countries. And while ingesting the crop products, these toxins get into the dietary system causing aflatoxicosis, liver cirrhosis, etc. Therefore, it is imperative to search for certain ways to control the spread of infections and/or production of these toxins which may also not harm the crop harvest. In this review, we are going to discuss some sustainable methods that can effectively control the spread of infection and inhibit the biosynthesis of aflatoxins.
Altered cognition and anxiety in adolescent offspring whose mothers underwent different-pattern maternal sleep deprivation, and cognition link to hippocampal expressions of Bdnf and Syt-1
Authors: Wei Ru-Meng , Zhang Yue-Ming , Li Yun , Wu Qi-Tao , Wang Ya-Tao , Li Xue-Yan , Li Xue-Wei , Chen Gui-Hai
Published: December 2022

Background

Inadequate sleep during pregnancy negatively affects the neural development of offspring. Previous studies have focused on the continuous sleep deprivation (CSD) paradigm, but the sleep pattern during late pregnancy is usually fragmented.

Objective

To compare the effects of CSD and fragmented sleep deprivation (FSD) in late pregnancy on emotion, cognition, and expression of synaptic plasticity-related proteins in offspring mice.

Methods

Pregnant CD-1 mice were either subjected to 3/6 h of CSD/FSD during gestation days 15–21, while those in the control group were left untreated. After delivery, the offspring were divided into five groups, i.e., control (CON), short or long CSD (CSD3h, CSD6h), and short or long FSD (FSD3h, FSD6h). When the offspring were 2 months old, the anxiety-like behavior level was tested using the open field (OF) and elevated plus maze (EPM) test, and spatial learning and memory were evaluated using the Morris water maze (MWM) test. The expression of hippocampal of brain-derived neurotrophic factor (Bdnf) and synaptotagmin-1 (Syt-1) was determined using RT-PCR and western blotting.

Results

The CSD6h, FSD3h, and FSD6h had longer latency, fewer center times in the OF test, less open arms time and fewer numbers of entries in the open arms of the EPM, longer learning distance swam and lower memory percentage of distance swam in the target quadrant in the MWM test, and decreased BDNF and increased Syt-1 mRNA and protein levels in the hippocampus. Compared to the CSD6h, the FSD3h and FSD6h had longer distance swam, a lower percentage of distance swam in the target quadrant, decreased BDNF, and increased Syt-1 mRNA and protein levels in the hippocampus.

Conclusion

The results suggested that maternal sleep deprivation during late pregnancy impairs emotion and cognition in offspring, and FSD worsened the cognitive performance to a higher extent than CSD. The observed cognitive impairment could be associated with the expression of altered hippocampal of Bdnf and Syt-1 genes.
Alzheimer’s disease like neuropathology in Down syndrome cortical organoids
Authors: Zhao Helen H. , Haddad Gabriel G.
Published: December 2022

Introduction: Down syndrome (DS) is a genetic disorder with an extra copy of chromosome 21 and DS remains one of the most common causes of intellectual disabilities in humans. All DS patients have Alzheimer’s disease (AD)-like neuropathological changes including accumulation of plaques and tangles by their 40s, much earlier than the onset of such neuropathological changes in AD patients. Due to the lack of human samples and appropriate techniques, our understanding of DS neuropathology during brain development or before the clinical onset of the disease remains largely unexplored at the cellular and molecular levels.

Methods: We used induced pluripotent stem cell (iPSC) and iPSC-derived 3D cortical organoids to model Alzheimer’s disease in Down syndrome and explore the earliest cellular and molecular changes during DS fetal brain development.

Results: We report that DS iPSCs have a decreased growth rate than control iPSCs due to a decreased cell proliferation. DS iPSC-derived cortical organoids have a much higher immunoreactivity of amyloid beta (Aß) antibodies and a significantly higher amount of amyloid plaques than control organoids. Although Elisa results did not detect a difference of Aß40 and Aß42 level between the two groups, the ratio of Aß42/Aß40 in the detergent-insoluble fraction of DS organoids was significantly higher than control organoids. Furthermore, an increased Tau phosphorylation (pTau S396) in DS organoids was confirmed by immunostaining and Western blot. Elisa data demonstrated that the ratio of insoluble Tau/total Tau in DS organoids was significantly higher than control organoids.

Conclusion: DS iPSC-derived cortical organoids mimic AD-like pathophysiologyical phenotype in vitro, including abnormal Aß and insoluble Tau accumulation. The molecular neuropathologic signature of AD is present in DS much earlier than predicted, even in early fetal brain development, illustrating the notion that brain organoids maybe a good model to study early neurodegenerative conditions.
Abnormal expression of cortical cell cycle regulators underlying anxiety and depressive-like behavior in mice exposed to chronic stress
Authors: Mendes-Silva Ana Paula , Prevot Thomas Damien , Banasr Mounira , Sibille Etienne , Diniz Breno Satler
Published: December 2022

Background

The cell cycle is a critical mechanism for proper cellular growth, development and viability. The p16INK4a and p21Waf1/Cip1 are important regulators of the cell cycle progression in response to internal and external stimuli (e.g., stress). Accumulating evidence indicates that the prefrontal cortex (PFC) is particularly vulnerable to stress, where stress induces, among others, molecular and morphological alterations, reflecting behavioral changes. Here, we investigated if the p16INK4a and p21Waf1/Cip1 expression are associated with behavioral outcomes.

Methods

Prefrontal cortex mRNA and protein levels of p16INK4A and p21Waf1/Cip1 of mice (six independent groups of C57BL/6J, eight mice/group, 50% female) exposed from 0 to 35 days of chronic restraint stress (CRS) were quantified by qPCR and Western Blot, respectively. Correlation analyses were used to investigate the associations between cyclin-dependent kinase inhibitors (CKIs) expression and anxiety- and depression-like behaviors.

Results

Our results showed that the PFC activated the cell cycle regulation pathways mediated by both CKIs p16INK4A and p21Waf1/Cip1 in mice exposed to CRS, with overall decreased mRNA expression and increased protein expression. Moreover, correlation analysis revealed that mRNA and protein levels are statistically significant correlated with anxiety and depressive-like behavior showing a greater effect in males than females.

Conclusion

Our present study extends the existing literature providing evidence that PFC cells respond to chronic stress exposure by overexpressing CKIs. Furthermore, our findings indicated that abnormal expression of p16INK4A and p21Waf1/Cip1 may significantly contribute to non-adaptive behavioral responses.
Effectiveness of contralaterally controlled functional electrical stimulation vs. neuromuscular electrical stimulation for recovery of lower extremity function in patients with subacute stroke: A randomized controlled trial
Authors: Huang Songhua , Zhang Yuqian , Liu Peile , Chen Yinglun , Gao Beiyao , Chen Chan , Bai Yulong
Published: December 2022

Objective

This study aimed to compare the efficacy of contralaterally controlled functional electrical stimulation (CCFES) vs. neuromuscular electrical stimulation (NMES) for motor recovery of the lower extremity in patients with subacute stroke.

Materials and methods

Seventy patients within 6 months post-stroke were randomly assigned to the CCFES group (n = 35) and the NMES group (n = 35). Both groups underwent routine rehabilitation plus 20-min electrical stimulation (CCFES or NMES) on ankle dorsiflexion muscles per day, 5 days a week, for 3 weeks. Ankle AROM (dorsiflexion), Fugl-Meyer assessment-lower extremity (FMA-LE), Barthel Index (BI), Functional Ambulation Category scale (FAC), 10-meter walking test, and surface electromyography (sEMG) were assessed at the baseline and at the end of the intervention.

Result

Ten patients did not complete the study (five in CCFES and five in NMES), so only 60 patients were analyzed in the end. After the 3-week intervention, FMA-LE, BI, Ankle AROM (dorsiflexion), and FAC increased in both groups (p < 0.05). Patients in the CCFES group showed significantly greater improvements only in the measurement of Fugl-Meyer assessment-lower extremity compared with the NMES group after treatment (p < 0.05). The improvement in sEMG response of tibialis anterior by CCFES was greater than NMES (p < 0.05).

Conclusion

Contralateral controlled functional electrical stimulation can effectively improve the motor function of the lower limbs better than conventional neuromuscular electrical stimulation in subacute patients after stroke, but the effect on improving the ability to walk, such as walking speed, was not good.

Clinical trial registration

http://www.chictr.org.cn/, identifier: ChiCTR2100045423.
Time-locked auditory cortical responses in the high-gamma band: A window into primary auditory cortex
Authors: Simon Jonathan Z. , Commuri Vrishab , Kulasingham Joshua P.
Published: December 2022

Primary auditory cortex is a critical stage in the human auditory pathway, a gateway between subcortical and higher-level cortical areas. Receiving the output of all subcortical processing, it sends its output on to higher-level cortex. Non-invasive physiological recordings of primary auditory cortex using electroencephalography (EEG) and magnetoencephalography (MEG), however, may not have sufficient specificity to separate responses generated in primary auditory cortex from those generated in underlying subcortical areas or neighboring cortical areas. This limitation is important for investigations of effects of top-down processing (e.g., selective-attention-based) on primary auditory cortex: higher-level areas are known to be strongly influenced by top-down processes, but subcortical areas are often assumed to perform strictly bottom-up processing. Fortunately, recent advances have made it easier to isolate the neural activity of primary auditory cortex from other areas. In this perspective, we focus on time-locked responses to stimulus features in the high gamma band (70–150 Hz) and with early cortical latency (∼40 ms), intermediate between subcortical and higher-level areas. We review recent findings from physiological studies employing either repeated simple sounds or continuous speech, obtaining either a frequency following response (FFR) or temporal response function (TRF). The potential roles of top-down processing are underscored, and comparisons with invasive intracranial EEG (iEEG) and animal model recordings are made. We argue that MEG studies employing continuous speech stimuli may offer particular benefits, in that only a few minutes of speech generates robust high gamma responses from bilateral primary auditory cortex, and without measurable interference from subcortical or higher-level areas.
Case report: An illusive cortical venous infarction mimicking glioma hemorrhage
Authors: Feng Dayun , Zou Le , Qin Huaizhou , Cai Qing
Published: December 2022

Cortical vein thrombosis (CVT) is a rare subtype of cerebral venous thrombosis. Because CVT is rare and its clinical and imaging findings are atypical, the misdiagnosis of CVT may be extremely high. We report a case of cortical venous infarction (CVI) secondary to CVT. Due to the atypical symptoms, we were perplexed about confirming the diagnosis between CVI and glioma hemorrhage. Eventually, CVT was confirmed by pathology combined with imaging.
Dual-function AAV gene therapy reverses late-stage Canavan disease pathology in mice
Authors: Fröhlich Dominik , Kalotay Elizabeth , von Jonquieres Georg , Bongers Andre , Lee Brendan , Suchowerska Alexandra K. , Housley Gary D. , Klugmann Matthias
Published: December 2022

The leukodystrophy Canavan disease is a fatal white matter disorder caused by loss-of-function mutations of the aspartoacylase-encoding ASPA gene. There are no effective treatments available and experimental gene therapy trials have failed to provide sufficient amelioration from Canavan disease symptoms. Preclinical studies suggest that Canavan disease-like pathology can be addressed by either ASPA gene replacement therapy or by lowering the expression of the N-acetyl-L-aspartate synthesizing enzyme NAT8L. Both approaches individually prevent or even reverse pathological aspects in Canavan disease mice. Here, we combined both strategies and assessed whether intracranial adeno-associated virus-mediated gene delivery to a Canavan disease mouse model at 12 weeks allows for reversal of existing pathology. This was enabled by a single vector dual-function approach. In vitro and in vivo biopotency assessment revealed significant knockdown of neuronal Nat8l paired with robust ectopic aspartoacylase expression. Following nomination of the most efficient cassette designs, we performed proof-of-concept studies in post-symptomatic Aspa-null mice. Late-stage gene therapy resulted in a decrease of brain vacuoles and long-term reversal of all pathological hallmarks, including loss of body weight, locomotor impairments, elevated N-acetyl-L-aspartate levels, astrogliosis, and demyelination. These data suggest feasibility of a dual-function vector combination therapy, directed at replacing aspartoacylase with concomitantly suppressing N-acetyl-L-aspartate production, which holds potential to permanently alleviate Canavan disease symptoms and expands the therapeutic window towards a treatment option for adult subjects.