bluuebunny/crossref_metadata_2025_split huggingface dataset:
A purified and lyophilized Pseudomonas aeruginosa derived pyocyanin induces promising apoptotic and necrotic activities against MCF-7 human breast adenocarcinoma
Authors: Abdelaziz Ahmed A. , Kamer Amal M. Abo , Al-Monofy Khaled B. , Al-Madboly Lamiaa A. 
Published: December 2022

Abstract
Background
Pyocyanin, a specific extracellular secondary metabolite pigment produced by Pseudomonas aeruginosa, exhibits redox activity and has toxic effects on mammalian cells, making it a new and potent alternative for treating cancer. Breast cancer (BC) treatment is now defied by acquired and de novo resistance to chemotherapy, radiation, or targeted therapies. Therefore, the anticancer activity of purified and characterized pyocyanin was examined against BC in our study.

Results
The maximum production of pyocyanin (53 µg/ml) was achieved by incubation of the highest pyocyanin-producing P. aeruginosa strain (P32) in pH-adjusted peptone water supplemented with 3% cetrimide under shaking conditions at 37 °C for 3 days. The high purity of the extracted pyocyanin was proven by HPLC against standard pyocyanin. The stability of pyocyanin was affected by the solvent in which it was stored. Therefore, the purified pyocyanin extract was lyophilized to increase its shelf-life up to one year. Using the MTT assay, we reported, for the first time, the cytotoxic effect of pyocyanin against human breast adenocarcinoma (MCF-7) with IC50 = 15 μg/ml while it recorded a safe concentration against human peripheral blood mononuclear cells (PBMCs). The anticancer potential of pyocyanin against MCF-7 was associated with its apoptotic and necrotic activities which were confirmed qualitatively and quantitively using confocal laser scanning microscopy, inverted microscopy, and flow cytometry. Caspase-3 measurements, using real-time PCR and western blot, revealed that pyocyanin exerted its apoptotic activity against MCF-7 through caspase-3 activation.

Conclusion
Our work demonstrated that pyocyanin may be an ideal anticancer candidate, specific to cancer cells, for treating MCF-7 by its necrotic and caspase-3-dependent apoptotic activities.
Emerging roles and mechanisms of miR-206 in human disorders: a comprehensive review
Authors: Khalilian Sheyda , Hosseini Imani Seyedeh Zahra , Ghafouri-Fard Soudeh 
Published: December 2022

AbstractAs a member of the miR-1 family, miR-206 is located between IL-17 and PKHD1 genes in human. This miRNA has been shown to be involved in the pathogenic processes in a variety of human disorders including cancers, amyotrophic lateral sclerosis, Alzheimer’s disease, atherosclerosis, bronchopulmonary dysplasia, coronary artery disease, chronic obstructive pulmonary disease, epilepsy, nonalcoholic fatty liver disease, Hirschsprung disease, muscular dystrophies, pulmonary arterial hypertension, sepsis and ulcerative colitis. In the current review, we summarize the role of miR-206 in both malignant and non-malignant situations and explain its possible therapeutic implications.
Dinuclear and mononuclear metal(II) polypyridyl complexes against drug-sensitive and drug-resistant Plasmodium falciparum and their mode of action
Authors: Lai Jing Wei , Maah Mohd Jamil , Tan Kong Wai , Sarip Rozie , Lim Yvonne Ai Lian , Ganguly Rakesh , Khaw Loke Tim , Ng Chew Hee 
Published: December 2022

Abstract
Background
Malaria remains one of the most virulent and deadliest parasitic disease in the world, particularly in Africa and Southeast Asia. Widespread occurrence of artemisinin-resistant Plasmodium falciparum strains from the Greater Mekong Subregion is alarming. This hinders the national economies, as well as being a major drawback in the effective control and elimination of malaria worldwide. Clearly, an effective anti-malarial drug is urgently needed.

Methods
The dinuclear and mononuclear copper(II) and zinc(II) complexes were synthesized in ethanolic solution and characterized by various physical measurements (FTIR, CHN elemental analysis, solubility, ESI-MS, UV-Visible, conductivity and magnetic moment, and NMR). X-ray crystal structure of the dicopper(II) complex was determined. The in vitro haemolytic activities of these metal complexes were evaluated spectroscopically on B+ blood while the anti-malarial potency was performed in vitro on blood stage drug-sensitive Plasmodium falciparum 3D7 (Pf3D7) and artemisinin-resistant Plasmodium falciparum IPC5202 (Pf5202) with fluorescence dye. Mode of action of metal complexes were conducted to determine the formation of reactive oxygen species using PNDA and DCFH-DA dyes, JC-1 depolarization of mitochondrial membrane potential, malarial 20S proteasome inhibition with parasite lysate, and morphological studies using Giemsa and Hoechst stains.

Results
Copper(II) complexes showed anti-malarial potency against both Pf3D7 and Pf5202 in sub-micromolar to micromolar range. The zinc(II) complexes were effective against Pf3D7 with excellent therapeutic index but encountered total resistance against Pf5202. Among the four, the dinuclear copper(II) complex was the most potent against both strains. The zinc(II) complexes caused no haemolysis of RBC while copper(II) complexes induced increased haemolysis with increasing concentration. Further mechanistic studies of both copper(II) complexes on both Pf3D7 and Pf5202 strains showed induction of ROS, 20S malarial proteasome inhibition, loss of mitochondrial membrane potential and morphological features indicative of apoptosis.

Conclusion
The dinuclear [Cu(phen)-4,4′-bipy-Cu(phen)](NO3)4 is highly potent and can overcome the total drug-resistance of Pf5202 towards chloroquine and artemisinin. The other three copper(II) and zinc(II) complexes were only effective towards the drug-sensitive Pf3D7, with the latter causing no haemolysis of RBC. Their mode of action involves multiple targets.

Graphical Abstract
Integrated multi-omic analysis of low-grade ovarian serous carcinoma collected from short and long-term survivors
Authors: Wong Kwong-Kwok , Bateman Nicholas W. , Ng Chun Wai , Tsang Yvonne T. M. , Sun Charlotte S. , Celestino Joseph , Nguyen Tri V. , Malpica Anais , Hillman R. Tyler , Zhang Jianhua , Futreal P. Andrew , Rojas Christine , Conrads Kelly A. , Hood Brian L. , Dalgard Clifton L. , Wilkerson Matthew D. , Phippen Neil T. , Conrads Thomas P. , Maxwell George L. , Sood Anil K. , Gershenson David M. 
Published: December 2022

Abstract
Background
Low-grade serous ovarian cancer (LGSOC) is a rare disease that occurs more frequently in younger women than those with high-grade disease. The current treatment is suboptimal and a better understanding of the molecular pathogenesis of this disease is required. In this study, we compared the proteogenomic analyses of LGSOCs from short- and long-term survivors (defined as < 40 and > 60 months, respectively). Our goal was to identify novel mutations, proteins, and mRNA transcripts that are dysregulated in LGSOC, particularly in short-term survivors.

Methods
Initially, targeted sequencing of 409 cancer-related genes was performed on 22 LGSOC and 6 serous borderline ovarian tumor samples. Subsequently, whole-genome sequencing analysis was performed on 14 LGSOC samples (7 long-term survivors and 7 short-term survivors) with matched normal tissue samples. RNA sequencing (RNA-seq), quantitative proteomics, and phosphoproteomic analyses were also performed.

Results
We identified single-nucleotide variants (SNVs) (range: 5688–14,833 per sample), insertion and deletion variants (indels) (range: 880–1065), and regions with copy number variants (CNVs) (range: 62–335) among the 14 LGSOC samples. Among all SNVs and indels, 2637 mutation sites were found in the exonic regions. The allele frequencies of the detected variants were low (median12%). The identified recurrent nonsynonymous missense mutations included KRAS, NRAS, EIF1AX, UBR5, and DNM3 mutations. Mutations in DNM3 and UBR5 have not previously been reported in LGSOC. For the two samples, somatic DNM3 nonsynonymous missense mutations in the exonic region were validated using Sanger sequencing. The third sample contained two missense mutations in the intronic region of DNM3, leading to a frameshift mutation detected in RNA transcripts in the RNA-seq data. Among the 14 LGSOC samples, 7754 proteins and 9733 phosphosites were detected by global proteomic analysis. Some of these proteins and signaling pathways, such as BST1, TBXAS1, MPEG1, HBA1, and phosphorylated ASAP1, are potential therapeutic targets.

Conclusions
This is the first study to use whole-genome sequencing to detect somatic mutations in LGSOCs with matched normal tissues. We detected and validated novel mutations in DNM3, which were present in 3 of the 14 samples analyzed. Additionally, we identified novel indels, regions with CNVs, dysregulated mRNA, dysregulated proteins, and phosphosites that are more prevalent in short-term survivors. This integrated proteogenomic analysis can guide research into the pathogenesis and treatment of LGSOC.
A novel frameshift variant in the ADA2 gene of a patient with a neurological phenotype: a case report
Authors: Lucane Z. , Davidsone Z. , Micule I. , Auzenbaha M. , Kurjane N. 
Published: December 2022

Abstract
Background
Adenosine deaminase 2 (ADA2) deficiency is an inherited autoinflammatory syndrome caused by a defect in the ADA2 gene. Most common manifestations include peripheral vasculopathy, early-onset stroke, immunodeficiency, and haematological manifestations. Patients with pathogenic variants that are more detrimental to ADA2’s enzymatic function (e.g. frameshift) have been reported to be prone to developing hematological phenotype. We report here the case of a 13-year-old Caucasian girl with a novel frameshift variant in the ADA2 gene and a clinical phenotype of early-onset stroke.

Case presentation
The patient was admitted to hospital with complaints of weakness in her right arm, unilateral facial weakness and speech problems. Her initial laboratory workup was normal; however, magnetic resonance imaging of her brain confirmed acute/subacute ischaemic changes in the posterior limb of the left-sided internal capsule and in the apical part of the thalamus. She also had manifestations of immunodeficiency – recurrent skin infections and otitis, chronic Molluscum contagiosum infection in anamnesis and B cell deficiency with a low level of serum IgA. The patient’s DNA was analysed and two pathogenic variants were identified in the ADA2 gene, confirming a diagnosis of adenosine deaminase 2 (ADA2) deficiency. While one of the variants (c.506G > A (p.Arg169Gln)) has been reported previously, the other one is a novel frameshift variant, namely, c.464del (p.Pro155Hisfs*29). The patient received stroke rehabilitation, which significantly improved her functional state. Tumour necrosis factor inhibitor and methotrexate treatment was commenced, and the patient has remained stable with no further ischaemic events.

Conclusions
Although rare, ADA2 deficiency should be considered in patients with early-onset stroke, especially with concomitant manifestations of inflammatory features or immunodeficiency. This case report extends the genotypic spectrum of ADA2 deficiency.
Poorer surgical outcomes at 2 years postoperatively in patients with lumbar spinal stenosis with long-term preoperative leg numbness: a single-center retrospective study
Authors: Li Kuan , Han Xiao , Chen Xin , Zhang Haozhi , Huang Changfa , Li Zheng 
Published: December 2022

Abstract
Background
The purpose of this study was to assess whether differences in duration of preoperative leg numbness lead to different surgical outcomes.

Methods
This study included patients with lumbar spinal stenosis (LSS) who underwent lumbar fusion surgery in our hospital from January 2018 to September 2020. Patients were divided into three groups based on duration of preoperative leg numbness: no numbness (NN) group, short-term numbness (STN) group (leg numbness ≤ 3 months) and long-term numbness (LTN) group (leg numbness > 3 months). The Numerical Rating Scale of leg pain (NRS-LP) and leg numbness (NRS-LN), Oswestry Disability Index (ODI) and Short-Form Health Survey (SF-36) were collected before surgery and at 3, 6, 12 and 24 months postoperatively.

Results
178 patients were included in this study. At 24 months postoperatively, NRS-LP was significantly higher in LTN than in NN [NN vs. STN vs. LTN: 0 (0,1) vs. 0 (0,1) vs. 1 (0,1)] (p = 0.033). NRS-LN in STN [2 (1,3)] was significantly lower than in LTN [3 (2,3)] (p < 0.001). SF-36 was significantly lower in LTN than in other two groups (NN vs. STN vs. LTN: 86.10 ± 6.02 vs. 84.09 ± 5.59 vs. 78.93 ± 6.57) (p < 0.001). ODI was significantly higher in LTN than in other two groups [NN vs. STN vs. LTN: 18 (15,22) vs. 18 (16,20) vs. 21 (19,24)] (p = 0.001).

Conclusions
Patients with LSS with long-term preoperative leg numbness have poorer outcomes at 2 years postoperatively. Surgical intervention should be performed before persistent leg numbness for more than 3 months to obtain a better prognosis.
A multidisciplinary care pathway improves quality of life and reduces pain in patients with fibrous dysplasia/McCune-Albright syndrome: a multicenter prospective observational study
Authors: Meier Maartje E. , Hagelstein-Rotman Marlous , van de Ven Annenienke C. , Van der Geest Ingrid C. M. , Donker Olav , Pichardo Sarina E. C. , Hissink Muller Petra C. E. , van der Meeren Stijn W. , Dorleijn Desirée M. J. , Winter Elizabeth M. , van de Sande Michiel A. J. , Appelman-Dijkstra Natasha M. 
Published: December 2022

Abstract
Background
Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) may cause pain, impaired ambulation and decreased quality of life (QoL). International guidelines advocate management of FD/MAS in a tertiary multidisciplinary care pathway, but no longitudinal data are available to support this recommendation. This multicenter prospective observational study aimed to evaluate effects of 1 year of treatment in the FD/MAS care pathway in 2 tertiary clinics on QoL and pain, assessed by change in Short Form 36 and Brief Pain Inventory between baseline and follow-up. Patients completing baseline questionnaires < 1 year after intake were classified as new referrals, others as under chronic care.

Results
92 patients were included, 61 females (66%). 22 patients (24%) had monostotic disease, 16 (17%) isolated craniofacial FD, 27 (40%) polyostotic FD and 17 (19%) MAS. 26 were new referrals (28%) and 66 chronic patients (72%). Median age at baseline was 47 years (Q1–Q3 36–56). Skeletal burden correlated with baseline Physical Function (rs = − 0.281, p = 0.007). QoL was in all domains lower compared to the general population. New referrals reported clinically important differences (CID) over time in domains Physical Function (mean 67 ± SD24 to 74 ± 21, effect size (ES) 0.31, p = 0.020), Role Physical (39 ± 41 to 53 ± 43, ES 0.35, p = 0.066), Social Functioning (64 ± 24 to 76 ± 23, ES 0.49, p = 0.054), and Health Change (39 ± 19 to 53 ± 24, ES 0.76, p = 0.016), chronic patients in Physical Function (52 ± 46 to 66 ± 43, ES 0.31, p = 0.023) and Emotional Wellbeing (54 ± 27 to 70 ± 15, ES 0.59, p < 0.001). New referrals reported a CID of 1 point in maximum pain, average pain and pain interference, chronic patients reported stable scores. Change in pain interference and Role Physical were correlated (rs = − 0.472, p < 0.001). Patients with limited disease extent improved more than patients with severe disease. Patients receiving FD-related therapy had lower baseline scores than patients not receiving therapy and reported improvements in QoL after 1 year. Yet also patients without FD-related therapy improved in Physical Function.

Conclusions
All FD-subtypes may induce pain and reduced QoL. A multidisciplinary care pathway for FD/MAS may improve pain and QoL, mainly in new referrals without MAS comorbidities with low baseline scores. Therefore, we recommend referral of patients with all subtypes of FD/MAS to specialized academic centers.
Foot self‐care competence reported by patients with rheumatoid arthritis: a cross‐sectional study
Authors: Laitinen Anne‐Marie , Pasanen Miko , Wasenius Elina , Stolt Minna 
Published: December 2022

AbstractBackgroundFoot self‐care is important for preventing foot problems and maintaining one's foot health. Foot self‐care requires competence to identify foot problems, knowledge and skills to care for those problems, and a willing attitude to care for one's foot health. However, there is major gap in the research evidence of foot self‐care competence among patients with rheumatoid arthritis. This study aimed to analyse self‐reported levels of competence in foot self‐care among patients with rheumatoid arthritis.MethodsA cross‐sectional study design was used. Data were collected using a survey consisting of a self‐reported competence in foot self‐care competence scale (response options on 5‐point Likert scale, higher values indicate higher competence) and background questions. The data were analysed with descriptive and inferential statistics and the psychometric properties of the scale using Rasch analysis.ResultsThe participants' (n = 251) self‐reported level of competence in foot self‐care was moderate (mean 3.50, standard deviation [SD], 0.66). On the sum variable level, the highest mean score was for attitude towards foot self‐care (3.98; SD, 0.69), followed by foot self‐care knowledge (3.45; SD, 0.67) and experience providing foot self‐care (3.38; SD, 0.69). Higher self‐reported foot self‐care knowledge and female sex were associated with higher self‐reported competence in every sum variable.ConclusionsPatients with rheumatoid arthritis evaluated their level of competence in foot self‐care as moderate and some deficiencies were identified. These results indicate the importance of educating patients with rheumatoid arthritis about how to advance their foot self‐care skills and knowledge. In the future, patients with rheumatoid arthritis could benefit from interventions that increase their knowledge of foot self‐care together with practical examples, such as online videos, that demonstrate the practical conduct of foot self‐care skills in daily life.
Ten rules for optimizing ventilatory settings and targets in post-cardiac arrest patients
Authors: Battaglini Denise , Pelosi Paolo , Robba Chiara 
Published: December 2022

AbstractCardiac arrest (CA) is a major cause of morbidity and mortality frequently associated with neurological and systemic involvement. Supportive therapeutic strategies such as mechanical ventilation, hemodynamic settings, and temperature management have been implemented in the last decade in post-CA patients, aiming at protecting both the brain and the lungs and preventing systemic complications. A lung-protective ventilator strategy is currently the standard of care among critically ill patients since it demonstrated beneficial effects on mortality, ventilator-free days, and other clinical outcomes. The role of protective and personalized mechanical ventilation setting in patients without acute respiratory distress syndrome and after CA is becoming more evident. The individual effect of different parameters of lung-protective ventilation, including mechanical power as well as the optimal oxygen and carbon dioxide targets, on clinical outcomes is a matter of debate in post-CA patients. The management of hemodynamics and temperature in post-CA patients represents critical steps for obtaining clinical improvement. The aim of this review is to summarize and discuss current evidence on how to optimize mechanical ventilation in post-CA patients. We will provide ten tips and key insights to apply a lung-protective ventilator strategy in post-CA patients, considering the interplay between the lungs and other systems and organs, including the brain.
ARDS: hidden perils of an overburdened diagnosis
Authors: Tobin Martin J. 
Published: December 2022

AbstractA diagnosis of ARDS serves as a pretext for several perilous clinical practices. Clinical trials demonstrated that tidal volume 12 ml/kg increases patient mortality, but 6 ml/kg has not proven superior to 11 ml/kg or anything in between. Present guidelines recommend 4 ml/kg, which foments severe air hunger, leading to prescription of hazardous (yet ineffective) sedatives, narcotics and paralytic agents. Inappropriate lowering of tidal volume also fosters double triggering, which promotes alveolar overdistention and lung injury. Successive panels have devoted considerable energy to developing a more precise definition of ARDS to homogenize the recruitment of patients into clinical trials. Each of three pillars of the prevailing Berlin definition is extremely flimsy and the source of confusion and unscientific practices. For doctors at the bedside, none of the revisions have enhanced patient care over that using the original 1967 description of Ashbaugh and colleagues. Bedside doctors are better advised to diagnose ARDS on the basis of pattern recognition and instead concentrate their vigilance on resolving the numerous hidden dangers that follow inevitably once a diagnosis has been made.
Parasite-host relationships of water mites (Acari: Hydrachnidia) and black flies (Diptera: Simuliidae) in southeastern Spain
Authors: López-Peña David , Gerecke Reinhard , García-Roger Eduardo Moisés , Martin Peter , Jiménez-Peydró Ricardo 
Published: December 2022

Abstract
Background
Documentation on water mites in Spain is scarce, as is information on the parasite-host relationship between certain water mite species and representatives of the dipteran family Simuliidae. The discomfort caused to humans and animals by black flies seems to be increasing in recent years. In this context, an investigation of parasitic water mites is of great importance, not only from the point of view of biodiversity, but also in terms of their potential to control black fly populations.

Methods
Rivers across a wide region of eastern Spain were sampled to determine the specific richness of simuliid dipterans and to investigate their possible parasites, such as water mites, mermithid nematodes and microsporidia (fungal microbes). Data on environmental variables, abundance, prevalence and intensity of parasitism on the collected specimens were analyzed.

Results
In 10 streams, 15,396 simuliid pupae were collected and checked for the presence of water mite larvae; 426 pupae in seven streams were found to be associated with water mite larvae. Of the 21 simuliid species identified based on morphological characters, eight were found to be associated with water mite larvae. Water mite infection was not equally distributed among black fly species. Also, the prevalence of parasitism was low and differed among simuliid species, ranging from one to 13 water mites per black fly pupa. Variation at the intra- and interspecific levels was detected in terms of the number of water mites inside the black fly cocoons. Free-living deutonymphal and adult water mites representing 15 different species of six genera and five families were morphologically identified. The taxonomic identity of the parasitic mite larvae is unclear at present. Morphologically, they fit descriptions of larval Sperchon (Hispidosperchon) algeriensis Lundblad, 1942, but the possibility cannot be excluded that they represent Sperchon algeriensis, the most abundant species at the adult stage in this study and unknown at the larval stage, or even another species of the genus. A molecular analysis produced for the first time cytochrome oxidase I gene sequences for S. algeriensis.

Conclusions
Our results contribute to current knowledge on Spanish Hydrachnidia and their relationships with simuliids as hosts. However, further research is needed to evaluate the diversity, distribution, bioecology and prevalence of this parasitism.

Graphical Abstract