bluuebunny/crossref_metadata_2025 huggingface dataset:
The quality of health information provided on web sites selling cannabis to consumers in Canada is poor
Authors: Ng Jeremy Y. , Tahir Umair , Lum Nicholas
Published: December 2022

Background

Cannabis is used by millions of people for both medical and recreational purposes, and this use is even greater in jurisdictions where it is legalized, such as Canada. Online cannabis vendors have gained popularity for purchasing cannabis due to easy access and convenience to consumers. The objective of this study was to evaluate the quality of health information provided by web sites of cannabis vendors selling products to Canadian consumers and to further identify trends in the information provided.

Methods

Six different searches were conducted on Google.ca, and the first 40 webpages of each search were screened for eligibility. A total of 33 unique web sites of cannabis vendors selling products to Canadian consumers were identified and included. The DISCERN instrument, which consists of 16 questions divided into three sections, was used to evaluate the quality of cannabis-related health information on these web sites.

Results

Across the 33 web sites, the average of the summed DISCERN scores was 36.83 (SD = 9.73) out of 75, and the mean score for the overall quality of the publication (DISCERN question 16) was 2.41 (SD = 0.71) out of 5. Many of these web sites failed to discuss uncertainties in research evidence on cannabis, the impact of cannabis use on quality of life, alternatives to cannabis use, risks associated with cannabis use, and lacked references to support claims on effects and benefits of use.

Conclusion

Our findings indicate that the quality of cannabis-related health information provided by online vendors is poor. Healthcare providers should be aware that patients may use these web sites as primary sources of information and appropriately caution patients while directing them to high-quality sources. Future research should serve to replicate this study in other jurisdictions and assess the accuracy of information provided by online cannabis vendors, as this was outside the scope of the DISCERN instrument.
Health economic analysis of third-line interventions in diffuse large B-cell lymphomas in Germany: applying the efficiency frontier
Authors: Jakobs Florian , Jeck Julia , Ahmadi Paymon , Kron Anna , Kron Florian
Published: December 2022

Background

In the past decades, highly innovative treatments in the field of diffuse large B-cell lymphoma (DLBCL) became available in clinical practice. The aim of this study was to assess the cost–benefit relation of third-line interventions in DLBCL from a German payer perspective.

Methods

Clinical benefit of allogeneic stem cell transplantation (alloSCT), chimeric antigen receptor T cells therapy (CAR T) [tisagenlecleucel (tisa-cel) and axicabtagene ciloleucel (axi-cel)] and best supportive care (BSC) was assessed in terms of median overall survival (median OS) derived from a systematic literature review in PubMed. Real-world treatment costs were retrieved from the university hospitals Cologne and Hamburg-Eppendorf. The cost–benefit relation was analysed using the efficiency frontier concept.

Results

Median OS varied from 6.3 months in BSC to 23.5 months in CAR T (axi-cel), while median real-world treatment costs ranged likewise widely from €26,918 in BSC to €340,458 in CAR T (axi-cel). Shown by the efficiency frontier, alloSCT and axi-cel were found as most efficient interventions.

Conclusion

The efficiency frontier supports the pricing of innovative therapies, such as third-line interventions in DLBCL, in relation to appropriate comparators. Yet, studies with longer follow-up periods are needed to include studies with unreached median OS and to reflect experiences gained with CAR T in clinical practice.
Spontaneous correction of scoliosis after curettage of spinal osteoid osteoma: How and when?
Authors: Pan Xiyu , Qiao Jun , Liu Zhen , Sun Xu , Zhu Zezhang
Published: December 2022

Background

Scoliosis behavior after curettage of spinal osteoid osteoma has been not clarified as most studies regarding scoliosis secondary to osteoid osteoma (OO) were case reports. The aims of this study were to investigate (1) clinical and radiographic features of scoliosis secondary to OO; (2) scoliosis behavior after Curettage of OO.

Methods

A retrospective study was performed at patients who were diagnosed as OO clinically or pathologically from July 1998 to December 2019 in a single institution. Age, gender, location of pain, location of lesion and curve pattern of scoliosis were collected preoperatively. Intraoperative blood loss, operation time and surgical complications were documented. VAS scores and curve magnitude were collected pre- and postoperatively and at last follow-up.

Results

The mean operation time was 124 ± 32 min and the average intraoperative blood loss was 274 ± 134 ml. The mean preoperative VAS score was 6.2 ± 2.7, and the mean postoperative VAS score was 2.1 ± 1.8. Thoracic scoliosis was improved from 22.7 ± 10.6° to 6.2 ± 4.3° after operation, and to 4.1 ± 4.3° at last follow-up. Lumbar scoliosis was improved from 18.1 ± 7.4° to 6.7 ± 5.2° after operation, and to 5.3 ± 3.9° at last follow-up. Trunk shift was improved from 34.7 ± 12.4  to 10.5 ± 7.2 mm after operation, and to 8.4 ± 5.6 mm at last follow-up. There was no significant differences as to sagittal radiographic parameters (P > 0.05).

Conclusion

Patients with spinal OO had a significantly high incidence of scoliosis. Patients could get rapid relief of pain and scoliosis with low occurrence. Night pain, pain at the concave side of curve, normal sagittal alignment could help differentiate it from scoliosis associated with lumbar disc herniation.
“I could have a proper ankle” – a qualitative study of patients' perceptions of total ankle replacement and ankle fusion surgery
Authors: Anderson Anna M. , Chapman Lara S. , Siddle Heidi J. , Watson Sue , Klugerman Jane , Antcliff Deborah , Keenan Anne‐Maree , Brockett Claire L.
Published: December 2022

Background

End‐stage ankle osteoarthritis typically causes severe pain and impaired function. Surgical treatment involves total ankle replacement (TAR) or ankle fusion. Definitive evidence about which procedure is optimal is lacking. No previous studies have thoroughly explored patients' experiences across the entire TAR/ankle fusion pathway. This study aimed to address this gap by exploring perceptions of surgery, education, rehabilitation and outcomes among patients who had undergone TAR or ankle fusion.

Methods

Seven participants were purposively selected from an orthopaedic centre in northern England (3 females, 4 males). Participants had undergone primary TAR without revision (n = 2), TAR requiring revision (n = 3) or ankle fusion (n = 2). Each participant completed a single semi‐structured interview. Interviews were digitally recorded, transcribed verbatim and analysed thematically.

Results

Three themes, each with two subthemes, were identified: decision‐making (seeking help; surgical options), perceptions of support (information/education; clinical support) and impact on the individual (personal circumstances and beliefs; post‐operative outcomes). Pain affecting participants' valued activities was key to their decision to seek help. Participants' decision between TAR and ankle fusion was influenced by multiple factors. Concerns regarding the lack of joint flexibility following fusion were highlighted, with some participants perceiving TAR as a “proper ankle” that would enable them to avoid limping. Participants obtained information from various sources, with most feeling that the education from their care team was inadequate. Participants' individual circumstances and beliefs influenced their decision‐making and perceptions of their post‐operative outcomes. Finally, whilst most participants were pleased with their outcomes, some experienced substantial ongoing problems such as difficulty walking and chronic pain.

Conclusions

This study demonstrates the importance of providing adequate education about TAR and ankle fusion to enable patients to make informed decisions. Most participants felt that the education and clinical support they received did not fully meet their needs. Participants' personal circumstances and beliefs had a strong influence on their decision‐making and perceptions of their post‐operative outcomes, highlighting the need to personally tailor education and clinical support. Future work with a larger sample of patients and other key stakeholders is required to develop consensus‐based guidelines on pre‐ and post‐operative support for patients undergoing TAR/ankle fusion.
The change in pediatric subject symptoms during the COVID-19 pandemic in China: an increase in cardiac consultation
Authors: Tang Yaqi , Ma Shujing , Luo Gang , Ji Zhixian , Zhao Shuiyan , Cao Yue , Pan Silin
Published: December 2022

Background

It is reported that the adverse impact of nonpharmaceutical interventions (NPIs) on the mental health of children and adolescents may lead to psychologically related disorders during the coronavirus disease 2019 (COVID-19) period. Subject symptoms such as chest pain, chest tightness, and palpitation may be related to increased stress and anxiety in children and adolescents. The present research aimed to determine the number of pediatric consults and etiology of subject symptoms during the COVID-19 pandemic period and compared it with the same timelines in 2019 and 2021 to discuss the impact of different periods on the organic disease onset of children with subject symptoms, especially in cardiac involvement.

Methods

Children who visited Qingdao Women and Children’s Hospital, Qingdao University between January 23 to April 30, 2019 (pre-COVID-19 period), January 23 to April 30, 2020 (COVID-19 period), and January 23 to April 30, 2021 (post-COVID-19 period) presenting chest pain, chest tightness, and palpitation were recruited. Information to determine gender, age, medical history, department for the initial visit, clinical manifestations, time from the latest onset to the visit, and diagnosis were recorded.

Result

A total of 891 patients were enrolled in the present study (514 males; median age: 7.72). One hundred twenty-three patients presented during the pre-COVID-19 period while 130 during the COVID-19 period, nevertheless, the number substantially increased during the post-COVID-19 period (n = 638). Cardiac etiology accounted for 1.68% (n = 15) of the patient population, including arrhythmias (n = 10, 1.12%), myocarditis (n = 4, 0.44%), and atrial septal defect (n = 1, 0.11%). There was no significant difference among groups in the distribution of organic etiology. The median time from the latest onset to the visit during the pre-COVID-19 period was 7 days compared to 10 days during the COVID-19 period and 3 days during the post-COVID period.

Conclusion

During the post-COVID-19 period, the median time from the latest onset to the visit was significantly shorter than that in the pre-COVID-19 period or COVID-19 period. The pediatric consult of children with subject symptoms presented increased substantially during the post-COVID-19 period, while there was no significant difference in the number of patients involving the cardiac disease. Clinicians ought to be more careful to screen heart diseases to prevent missed diagnosis and misdiagnosis during special periods.
Application of Box-Behnken experimental design and response surface methodology for selecting the optimum RP-HPLC conditions for the simultaneous determination of methocarbamol, indomethacin and betamethasone in their pharmaceutical dosage form
Authors: Elkady Ehab F. , Fouad Marwa A. , Mozayad Ayoub N.
Published: December 2022

An isocratic RP-HPLC method has been developed for the separation and determination of methocarbamol (MTL), indomethacin (IND), and betamethasone (BET) in combined dosage form using an Inertsil ODS-3v C18 (250 × 4.6 mm, 5 μm) column with UV- detection at 235 nm. Experimental design using Box-Behnken design (BBD) was applied to study the response surface during method optimization and to achieve a good separation with a minimum number of experimental runs. The three independent parameters were pH of buffer, % of acetonitrile and flow rate of the mobile phase while the peak resolution of IND from MTL and the peak resolution of BET from IND (R2) were taken as responses to obtain mathematical models. The composite desirability was employed to optimize a set of responses overall (peak resolutions). The predicted optimum assay conditions include a mobile phase composition of acetonitrile and phosphate buffer (pH 5.95) in a ratio of 79:21,v/v, pumped at a flow rate of 1.4 mL min−1. With this ideal condition, the optimized method was able to achieve baseline separation of the three drugs with good resolution and a total run time of less than 7 min. The linearity of MTL, IND, and BET was determined in the concentration ranges of 5–600 µg mL− 1, 5–300 µg mL− 1, and 5–300 µg mL− 1and the regression coefficients were 0.9994, 0.9998, and 0.9998, respectively. The average percent recoveries for the accuracy were determined to be 100.41 ± 0.60%, 100.86 ± 0.86%, and 100.99 ± 0.65% for MTL, IND, and BET, respectively. The R.S.D.% of the intra-day precision was found to be less than 1%, while the R.S.D.% of the inter-day precision was found to be less than 2%. The RP-HPLC method was fully validated with regard to linearity, accuracy, precision, specificity, and robustness as per ICH recommendations. The proposed method has various applications in quality control and routine analysis of the investigated drugs in their pharmaceutical dosage forms and laboratory-prepared mixtures with the goal of reducing laboratory waste, analysis time, and effort.
The 2021–2022 position of Brazilian Diabetes Society on insulin therapy in type 1 diabetes: an evidence-based guideline to clinical practice
Authors: Silva Júnior Wellington S. , Gabbay Monica Andrade Lima , Lamounier Rodrigo Nunes , Calliari Luis Eduardo , Bertoluci Marcello Casaccia
Published: December 2022

Background

Insulin therapy regimens for people with type 1 diabetes (PWT1D) should mimic the physiological insulin secretion that occurs in individuals without diabetes. Intensive insulin therapy, whether by multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII), constitutes the fundamental therapy from the initial stages of type 1 diabetes (T1D), at all ages. This review is an authorized literal translation of part of the Brazilian Diabetes Society (SBD) Guidelines 2021–2022. This evidence-based guideline supplies guidance on insulin therapy in T1D.

Methods

The methods were published elsewhere in earlier SBD guidelines and was approved by the Internal Institutional Steering Committee for publication. Briefly, the Brazilian Diabetes Society indicated fourteen experts to constitute the Central Committee, designed to regulate the method review of the manuscripts, and judge the degrees of recommendations and levels of evidence. SBD Type 1 Diabetes Department drafted the manuscript selecting key clinical questions to do a narrative review using MEDLINE via PubMed, with the best evidence available, including high-quality clinical trials, metanalysis, and large observational studies related to insulin therapy in T1D, by using the Mesh terms [type 1 diabetes] and [insulin].

Results

Based on extensive literature review the Central Committee defined ten recommendations. Three levels of evidence were considered: A. Data from more than one randomised clinical trial (RCT) or one metanalysis of RCTs with low heterogeneity (I2 < 40%). B. Data from metanalysis, including large observational studies, a single RCT, or a pre-specified subgroup analysis. C: Data from small or non-randomised studies, exploratory analysis, or consensus of expert opinion. The degree of recommendation was obtained based on a poll sent to the panellists, using the following criteria: Grade I: when more than 90% of agreement; Grade IIa if 75–89% of agreement; IIb if 50–74% of agreement, and III, when most of the panellist recommends against a defined treatment.

Conclusions

In PWT1D, it is recommended to start insulin treatment immediately after clinical diagnosis, to prevent metabolic decompensation and diabetic ketoacidosis. Insulin therapy regimens should mimic insulin secretion with the aim to achieve glycemic control goals established for the age group. Intensive treatment with basal-bolus insulin therapy through MDI or CSII is recommended, and insulin analogues offers some advantages in PWT1D, when compared to human insulin. Periodic reassessment of insulin doses should be performed to avoid clinical inertia in treatment.
Anti-biofilm activity of Pseudomonas fluorescens culture supernatants on biofilm formation of Staphylococcus epidermidis 1457
Authors: Choi Euna , Wells Bethany , Mirabella Gabrielle , Atkins Emilee , Choi Sunga
Published: December 2022

Objective

Staphylococcus epidermidis is a skin colonizer and a major cause of nosocomial infections that can lead to sepsis. It causes opportunistic infections by forming biofilms on medical devices, which are hard to control with conventional antibiotics. In an attempt to develop its biofilm inhibitors, the culture supernatant (CS) of Pseudomonas fluorescens was assessed. This study examined the effect of the CS on S. epidermidis 1457 biofilm formation, the characteristics of inhibitors in the CS, and the differential gene expression of S. epidermidis when treated with the CS.

Results

P. fluorescens CS specifically targeted the maturation stage of S. epidermidis biofilm formation while not affecting planktonic growth. RT-qPCR analysis revealed that P. fluorescens CS significantly downregulated S. epidermidis ica genes and upregulated an ica repressor, tcaR. This indicates that the CS reduced polysaccharide intercellular adhesin synthesis, a major component of the S. epidermidis 1457 biofilm matrix. Further studies are required to elucidate the specific inhibitory components in the CS and their mechanism of action. Our results indicate that inhibitors in the P. fluorescens CS may have a significant value for inhibiting S. epidermidis biofilm. Combinations of specific inhibitors from the CS and antibiotics against staphylococci may provide an effective measure to control S. epidermidis biofilm formation while avoiding antibiotic resistance and compensating the attenuated effectiveness of antibiotics on biofilms.
Competition for recruitment in SARS-CoV-2 Trials in the United States: a longitudinal cohort analysis
Authors: Hutchinson Nora , Klas Katarzyna , Carlisle Benjamin G. , Polak Maciej , Kimmelman Jonathan , Waligora Marcin
Published: December 2022

Objective

Competition among trials for patient enrollment can impede recruitment. We hypothesized that this occurred early in the COVID-19 pandemic, when an unprecedented number of clinical trials were launched. We performed a simple and multivariable regression analysis evaluating the relationship between the proportion of SARS-CoV-2 investigational trial sites within each USA state with unsuccessful patient-participant recruitment and: (i) the proportion of cases required to reach state recruitment goals; (ii) state population based on data from the US Census; and, (iii) number of trial sites per state.

Results

Our study included 151 clinical trials. The proportion of trials with successful recruitment was 72.19% (109 of 151 trials). We did not find a significant relationship between unsuccessful patient-participant recruitment, state recruitment goals, state population or the number of trial sites per state in both our simple and multivariable regression analyses. Our results do not suggest that early in the COVID-19 pandemic, competition for patient-participants impeded successful recruitment in SARS-CoV-2 trials. This may reflect the unique circumstances of the first few months of the pandemic in the United States, in which the number and location of SARS-CoV-2 cases was sufficient to meet trial recruitment requirements, despite the large number of trials launched.
Erysipelothrix rhusiopathiae-specific T-cell responses after experimental infection of chickens selectively bred for high and low serum levels of mannose-binding lectin
Authors: Wattrang Eva , Sørensen Dalgaard Tina , Brødsgaard Kjaerup Rikke , Naghizadeh Mohammad , Kabell Susanne , Eriksson Helena , Söderlund Robert
Published: December 2022

Erysipelas, caused by infection with Erysipelothrix rhusiopathiae (ER) is an important emerging disease in laying hens. We have earlier observed prominent mannose-binding lectin (MBL) acute phase responses in experimentally ER infected chickens. The present study aimed to further examine immune responses to ER by using chickens selectively bred for high (L10H) and low (L10L) serum MBL levels. Chickens were infected with ER at 3 weeks of age and immune parameters and bacterial load were monitored in blood until day 18 after infection. Blood and spleen leukocytes collected on day 18 were stimulated in vitro with ER antigens and blast transformation of different T-cell populations was assessed. The ER infection gave a very varied outcome and no clear differences were observed between L10H and L10L chickens with respect to leukocyte counts, bacterial load or clinical outcome. Nonetheless, rapid innate responses, e.g., heterophilia and increased serum MBL levels were noted in bacteraemic chickens. All ER infected chickens also showed transient increased expression of mannose receptor MRC1L-B and decreased expression of major histocompatibility complex II on monocytes day 1 after infection indicating monocyte activation or relocation. In vitro ER stimulation showed antigen specific blast transformation of CD4+, TCRγ/δ−CD8αβ+ and TCRγ/δ+CD8αβ+ spleen cells from all infected chickens. For CD4+ and TCRγ/δ−CD8αβ+ cells the proportions of blast transformed cells were significantly higher for samples from L10L chickens than those for samples from L10H chickens. This is the first observation of ER-specific T-cells in chickens and interestingly a Th1-type response comprising cytotoxic T-cells was indicated.
Main actors in the new population policy with a growing trend in Iran: a stakeholder analysis
Authors: Jafari Hasan , Pourreza Abolghasem , Kabiri Neda , Khodyari-Zarnaq Rahim
Published: December 2022

The total fertility rate in Iran has declined to below replacement level recently, and a new approach has been taken to tackle this issue. Thus, this study aimed to identify the involved stakeholders and their characteristics in the new population policy change in Iran. We employed a qualitative approach using the purposive sampling of key informants and the identification of relevant documents. The main stakeholders were divided into seven key groups: religious, political, governmental, professional, international sectors, media, and nongovernmental organizations. In addition, there was no centralized, clear, and comprehensive mechanism to guide the activities of stakeholders to coordinate and bring the total fertility rate to the replacement level in Iran. Despite the importance of the new population policy in Iran, in recent years, we still experience dispersion and inconsistency among various actors in this area. It is imperative to go through a consensus and coalition at macro-level authorities alongside evidenced-based population policymaking.
Glycopeptide antibiotic drug stability in aqueous solution
Authors: Jakaria Sardar M. , Budil David E. , Murtagh James
Published: December 2022

Glycopeptide antimicrobials are a class of naturally occurring or semi-synthetic glycosylated products that have shown antibacterial activity against gram-positive organisms by inhibiting cell-wall synthesis. In most cases, these drugs are prepared in dry powder (lyophilized) form due to chemical and physical instability in aqueous solution; however, from an economic and practical point of view, liquid formulations are preferred. Researchers have recently found ways to formulate some glycopeptide antibiotic therapeutic drugs in aqueous solution at refrigerated or room temperature. Chemical degradation can be significantly slowed by formulating them at a defined pH with specific buffers, avoiding oxygen reactive species, and minimizing solvent exposure. Sugars, amino acids, polyols, and surfactants can reduce physical degradation by restricting glycopeptide mobility and reducing solvent interaction. This review focuses on recent studies on glycopeptide antibiotic drug stability in aqueous solution. It is organized into three sections: (i) glycopeptide antibiotic instability due to chemical and physical degradation, (ii) strategies to improve glycopeptide antibiotic stability in aqueous solution, and (iii) a survey of glycopeptide antibiotic drugs currently available in the market and their stability based on published literature and patents. Antimicrobial resistance deaths are expected to increase by 2050, making heat-stable glycopeptides in aqueous solution an important treatment option for multidrug-resistant and extensively drug-resistant pathogens. In conclusion, it should be possible to formulate heat stable glycopeptide drugs in aqueous solution by understanding the degradation mechanisms of this class of therapeutic drugs in greater detail, making them easily accessible to developing countries with a lack of cold chains.
Comparison of mammosphere formation from stem-like cells of normal breast, malignant primary breast tumors, and MCF-7 cell line
Authors: Ambrose Jenifer Mallavarpu , Veeraraghavan Vishnu Priya , Vennila Rosy , Rupert Secunda , Sathyanesan Jeswanth , Meenakshisundaram Rajasundari , Selvaraj Sakthivel , Malayaperumal Sarubala , Kullappan Malathi , Dorairaj Sudarsanam , Gujarathi Jayesh R. , Gandhamaneni Sri Harshini , Surapaneni Krishna Mohan
Published: December 2022

Background

Mammosphere formation assay has become a versatile tool to quantify the activity of putative breast cancer stem cells in non-adherent in vitro cultures. However, optimizing the suspension culture system is crucial to establish mammosphere cultures from primary breast tumors.

Methods

This study aimed at determining the self-renewal and sphere-forming potential of breast cancer stem-like cells derived from human primary invasive ductal carcinoma and normal breast tissue samples, and MCF-7 breast cancer cell line using an optimal suspension culture system. Mammosphere-forming efficiency of the mammospheres generated from the tissue samples and cell line were compared. We evaluated the expression of CD44+/CD24−/low and CD49f+/EpCAM−/low phenotypes in the stem-like cells by flow cytometry. CK-18, CK-19, α-SMA, and EpCAM marker expression was assessed using immunohistochemical staining.

Results

Breast epithelial cells isolated from the three samples formed two-dimensional spheroids in suspension cultures. Interestingly, mammospheres formed from patient-derived primary breast tumors were enriched in breast cancer stem-like cells with the phenotype CD44+/CD24−/low and exhibited a relatively more number of large spheres when compared to the normal breast stem cells. MCF-7-derived SCs were more aggressive and resulted in the formation of a significantly higher number of spheroids. The expression of CK-18/CK-19 and α-SMA/EpCAM proteins was confirmed in breast cancer tissues.

Conclusions

Thus, the use of primary tumor specimens and breast cancer cell lines as suitable models for elucidating the breast cancer stem cell activity was validated using mammosphere culture system.
Nivolumab and Doxorubicin, Vinblastine, and Dacarbazine in Early-Stage Unfavorable Hodgkin Lymphoma: Final Analysis of the Randomized German Hodgkin Study Group Phase II NIVAHL Trial
Authors: Bröckelmann Paul J. , Bühnen Ina , Meissner Julia , Trautmann-Grill Karolin , Herhaus Peter , Halbsguth Teresa V. , Schaub Valdete , Kerkhoff Andrea , Mathas Stephan , Bormann Matthias , Dickhut Andreas , Kaul Helen , Fuchs Michael , Kobe Carsten , Baues Christian , Borchmann Peter , Engert Andreas , von Tresckow Bastian
Published: December 2022

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.

In the investigator-sponsored randomized phase II NIVAHL trial for early-stage unfavorable classical Hodgkin lymphoma (HL), two schedules of four cycles of nivolumab, doxorubicin, vinblastine, and dacarbazine followed by 30 Gy involved-site radiotherapy resulted in high complete remission rates and an unprecedented 1-year progression-free survival in 109 patients. In this article, we report the preplanned final analysis conducted three years after the registration of the last patient including long-term safety results. No survival events were observed since the primary analysis, and after a median follow-up (FU) of 41 months, the overall survival was 100% in both treatment groups. The progression-free survival was 98% and 100% in the sequential and concomitant nivolumab, doxorubicin, vinblastine, and dacarbazine treatment groups, respectively. At last FU, the mean forced expiratory pressure in one second was 95.5% (standard deviation 12.7%), the mean diffusion capacity for carbon monoxide adjusted for hemoglobin was 82.8% (standard deviation 15.4%), and the left ventricular ejection fraction was in the normal range in 95% of patients. Hypothyroidism requiring long-term medication occurred in 15% of patients, who were nearly exclusively female (87%). No second primary malignancies occurred, and no patient required corticosteroid treatment at last FU. Patient-reported normalized global quality-of-life score measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 improved over time. This preplanned FU analysis of the largest anti–programmed death protein 1 HL first-line trial to date confirms the outstanding efficacy and relatively favorable safety profile of this therapeutic approach.
Growth Hormone–Releasing Hormone in Endothelial Inflammation
Authors: Barabutis Nektarios , Akhter Mohammad S , Kubra Khadeja-Tul , Jackson Keith
Published: December 2022

The discovery of hypothalamic hormones propelled exciting advances in pharmacotherapy and improved life quality worldwide. Growth hormone–releasing hormone (GHRH) is a crucial element in homeostasis maintenance, and regulates the release of growth hormone from the anterior pituitary gland. Accumulating evidence suggests that this neuropeptide can also promote malignancies, as well as inflammation. Our review is focused on the role of that 44 - amino acid peptide (GHRH) and its antagonists in inflammation and vascular function, summarizing recent findings in the corresponding field. Preclinical studies demonstrate the protective role of GHRH antagonists against endothelial barrier dysfunction, suggesting that the development of those peptides may lead to new therapies against pathologies related to vascular remodeling (eg, sepsis, acute respiratory distress syndrome). Targeted therapies for those diseases do not exist.
Do Corticosteroid Receptor mRNA Levels Predict the Expression of Their Target Genes?
Authors: Koorneef Lisa L , Viho Eva M G , Wahl Lucas F , Meijer Onno C
Published: December 2022

The glucocorticoid stress hormones affect brain function via high-affinity mineralocorticoid receptors (MRs) and lower-affinity glucocorticoid receptors (GRs). MR and GR not only differ in affinity for ligands, but also have distinct, sometimes opposite, actions on neuronal excitability and other cellular and higher-order parameters related to cerebral function. GR and MR messenger RNA (mRNA) levels are often used as a proxy for the responsiveness to glucocorticoids, assuming proportionality between mRNA and protein levels. This may be especially relevant for the MR, which because of its high affinity is already largely occupied at low basal (trough) hormone levels. Here we explore how GR and MR mRNA levels are associated with the expression of a shared target gene, glucocorticoid-induced leucine zipper (GILZ, coded by Tsc22d3) with basal and elevated levels of corticosterone in male mice, using in situ hybridization. Depending on the hippocampal subfield and the corticosterone levels, mRNA levels of MR rather than GR mostly correlated with GILZ mRNA in the hippocampus and hypothalamus at the bulk tissue level. At the individual cell level, these correlations were much weaker. Using publicly available single-cell RNA sequencing data, we again observed that MR and GR mRNA levels were only weakly correlated with target gene expression in glutamatergic and GABAergic neurons. We conclude that MR mRNA levels can be limiting for receptor action, but many other cell-specific and region-specific factors ultimately determine corticosteroid receptor action. Altogether, our results argue for caution while interpreting the consequences of changed receptor expression for the response to glucocorticoids.
Diversity of mitophagy pathways at a glance
Authors: Ganley Ian G. , Simonsen Anne
Published: December 2022

Mitochondria are crucial organelles that play a central role in various cell signaling and metabolic pathways. A healthy mitochondrial population is maintained through a series of quality control pathways and requires a fine-tuned balance between mitochondrial biogenesis and degradation. Defective targeting of dysfunctional mitochondria to lysosomes through mitophagy has been linked to several diseases, but the underlying mechanisms and the relative importance of distinct mitophagy pathways in vivo are largely unknown. In this Cell Science at a Glance and the accompanying poster, we describe our current understanding of how parts of, or whole, mitochondria are recognized by the autophagic machinery and targeted to lysosomes for degradation. We also discuss how this might be regulated under different physiological conditions to maintain mitochondrial and cellular health.
Γονικές επιρροές στη βαθμολόγηση των μαθητών της δευτεροβάθμιας εκπαίδευσης
Authors: Παπακωνσταντίνου Αντιγόνη Άλμπα
Published: December 2022

Το άρθρο αυτό επιχειρεί να κατανοήσει τους τρόπους με τους οποίους οι γονείς των μαθητών επηρεάζουν τη βαθμολόγηση των εκπαιδευτικών της δευτεροβάθμιας εκπαίδευσης. Κατά τη θεωρητική πλαισίωση της έρευνας προσδιορίζεται ο κοινωνικός ρόλος των εκπαιδευτικών της δευτεροβάθμιας ως δρώντων στο σχολείο, το οποίο εκλαμβάνεται ως πεδίο δράσης και αλληλεπίδρασης, και στοχευμένα περιγράφεται η γονική εμπλοκή στο γυμνάσιο και το λύκειο. Έπειτα, μέσα από μία θεματική ανάλυση  ημιδομημένων συνεντεύξεων με ομάδες εστίασης, τις οποίες απαρτίζουν είκοσι εκπαιδευτικοί ποικίλων ειδικοτήτων της δευτεροβάθμιας, εκτίθενται οι απόψεις των συμμετεχόντων, σχετικά με τους τρόπους, με τους οποίους οι γονείς των μαθητών εκδηλώνουν το ενδιαφέρον τους για τους βαθμούς των παιδιών τους, καθώς επίσης και σχετικά με τα μέσα που χρησιμοποιούν, προκειμένου να ασκήσουν επιρροή στο βαθμολογικό έργο των εκπαιδευτικών. Όπως διαφαίνεται, οι εκπαιδευτικοί επηρεάζονται από τις παρεμβάσεις, τις επαφές ή την πίεση για τη βέλτιστη δυνατή βαθμολογία που ασκούν οι γονείς, ενώ το μέγεθος της επιρροής αυτής εξαρτάται από σύνθετους και ποικίλους παράγοντες, που αφορούν περιπτωσιολογικά σε όλους τους εμπλεκόμενους στη διαδικασία της βαθμολόγησης.
Απόψεις εκπαιδευτικών για την ένταξη των μεταναστών και προσφύγων και την ελληνική εκπαιδευτικής πολιτική.
Authors: Γιαβρίμης Παναγιώτης
Published: December 2022

Σκοπός της εργασίας ήταν η διερεύνηση των απόψεων των εκπαιδευτικών της Α/θμιας και Β/θμιας εκπαίδευσης σχετικά με την ένταξη μεταναστών/προσφύγων στο ελληνικό σχολείο. Στην έρευνα πήραν μέρος 22 εκπαιδευτικοί Α/θμιας και Β/θμιας εκπαίδευσης, 8 άντρες και 14 γυναίκες με πολυετή προϋπηρεσία στο δημόσιο σχολείο. Για την συλλογή των δεδομένων της έρευνας επιλέχθηκε η ποιοτική έρευνα μέσω του εργαλείου της ημιδομημένης συνέντευξης. Από την έρευνά μας διαφάνηκε ότι η πλειονότητα των εκπαιδευτικών της Α/θμιας και Β/θμιας εκπαίδευσης προσέγγισαν θετικά για την ένταξη των μεταναστών/προσφύγων στην εκπαίδευση, γιατί είναι δικαίωμα τους και έχει θετικές συνέπειες στην κοινωνική και εκπαιδευτική ανάπτυξη όλων των μαθητών. Επιπλέον, θεώρησαν την εκμάθηση της ελληνικής γλώσσας ως βασική μεταβλητή στη μαθησιακή και κοινωνική προσαρμογή των μαθητών με μεταναστευτικό και προσφυγικό υπόβαθρο. Επιπρόσθετα, μερικοί εκπαιδευτικοί είχαν στερεοτυπικές αντιλήψεις και εξέφρασαν ένα λόγο με εθνοκεντρικές διαστάσεις. Οι παραπάνω απόψεις διαμεσολαβούνται από τη μη κατάλληλα οργανωμένη εκπαιδευτική πολιτική (π.χ. ελλιπή επιμόρφωση και υλικοτεχνική υποδομή κ.λπ. ).
Übergang vom Kindergarten zur Grundschule: Der Fall Deutschland
Authors: Καινούργιου Ελένη , Δήμα Ευφροσύνη
Published: December 2022

Η απαίτηση συνεργασίας μεταξύ προσχολικών κέντρων και δημοτικών σχολείων δεν είναι νέα και έχει γίνει σημαντικό πεδίο έρευνας στα γερμανικά δημοτικά σχολεία τα τελευταία χρόνια. Σε αντίθεση με τη Γερμανία, ελάχιστη έρευνα έχει διεξαχθεί σε άλλες χώρες, συγκεκριμένα στην Ελλάδα, σχετικά με τη μετάβαση και την προσαρμογή των παιδιών από την προσχολική στην πρωτοβάθμια εκπαίδευση. Συμπερασματικά, σύμφωνα με τα δεδομένα της έρευνάς μας, η επιτυχής αντιμετώπιση των μεταβάσεων έχει αντίκτυπο στην περαιτέρω ανάπτυξη των παιδιών. Για το λόγο αυτό, ο χρόνος μετάβασης δεν πρέπει να βαρύνει μόνο το προσχολικό κέντρο και τους γονείς, αλλά και την έγκαιρη συνεργασία με το σχολείο. Ωστόσο, μπορεί να συναχθεί το συμπέρασμα ότι σήμερα υπάρχει συνεργασία μεταξύ των δύο δομών, αλλά εξακολουθεί να υπάρχει ένα ευρύ φάσμα ανασταλτικών παραγόντων, όπως η έλλειψη χρόνου του εκπαιδευτικού προσωπικού, προβλήματα κατάστασης (διαφορετικά εκπαιδευτικά μαθήματα και αμοιβές), οργανωτικά και προβλήματα συντονισμού μεταξύ των εκπαιδευτικών (νηπιαγωγείου και δημοτικού), έλλειψη γνώσεων σχετικά με μορφές συνεργασίας και έλλειψη συνέχειας όσον αφορά το περιεχόμενο, που εμποδίζουν την ομαλή συνεργασία.
PRICE FUNCTION DEVELOPMENT USING INDEPENDENT VARIABLES OF DEMAND AND SUPPLY IN THE CONDITIONS OF ECONOMY DIGITALIZATION
Authors: Vetrenko Vladimir I. , Romanova Tatyana I.
Published: December 2022

In modern world, under the pressure of buyers on retailers, the main foundations of classical marketing collapse and businesses need to master new pricing tools. Armed with new technologies and techniques, you can effectively influence the economic performance of an enterprise. Therefore, the development of new pricing methods in digital economy is not only an urgent task, but also necessary in the daily activities of business entities. The article describes a price function development model using the main parameters of supply and demand and the generalized Hooke’s law, as the closest one to display the processes of its state. Formulas are given to determine the price and its constituent parameters, taking into account supply and demand indicators, at which it becomes unprofitable for a seller to increase the amount of profit, and to increase the volume of consumption for a consumer. The results obtained allow trading and manufacturing companies during the period of economy digitalization, together with the involvement of financiers and IT experts, to automate the process of calculation and construction of retail prices for their products and move away from manual modeling of these parameters.

Purpose is to find, as a first approximation, a mathematical expression of the price, taking into account supply and demand indicators, at which it becomes unprofitable for a seller to increase the amount of profit, and it becomes unprofitable for a consumer to increase the volume of consumption.

Methodology: the article describes a model for a price function development using the main parameters of supply and demand and the generalized Hooke’s law.

Results: the results obtained allow us to predict profit taking into account the state of demand, while the price of a product may differ significantly from the price calculated by the classical method at the same costs.

Practical implication: it is advisable to apply the obtained results for automated calculation and modeling of retail prices for products.
On the Initial Stage of the Formation of Cognitive Universal Educational Activities in First-Graders in Mathematics Lessons
Authors: Fedorova N.
Published: December 2022

The article is devoted to the propaedeutics of the formation of cognitive universal educational activities among first-graders. The features of logical operations and information actions that are mastered by children in the process of working with a variety of mathematical material are characterized. It is considered as the most relevant for achieving the goal. Examples of tasks that a teacher can use in mathematics lessons in the first grade are given, adapting the degree of their complexity in accordance with the level of readiness of students.
Formation of the Initial Foundations of Ecological Culture Among Primary Schoolchildren: Examples of Methodological Developments
Authors: Artyuhova I.
Published: December 2022

The article discusses the problem of increasing attention to the environmental education of primary school students in accordance with the updated version of the State Educational Standard for Primary General Education (FSES PGE). The goals, methods and techniques of the process of formation of the ecological culture of younger schoolchildren at the lessons of the "The-World-Around-Us" are characterized. Examples of methodological developments in the study of various topics of this training course for the second grade are described. Particular attention is paid to familiarization with the Red Data Book of Russia and the regions.
Potencjał militarny Królestwa Polskiego w 1819 roku w oczach pruskiego oficera
Authors: Jędrysiak Jacek
Published: December 2022

We wrześniu 1819 r. na ręce pruskiego ministra wojny Hermanna von Boyen wpłynął list dotyczący sytuacji w Królestwie Polskim. Jego autorem był gen. Ludwig Gustav von Thile I, który dokonał rzeczowej analizy kluczowych elementów potencjału militarnego wschodniego sąsiada. List jest ważnym świadectwem naznaczonych nieufnością relacji polsko-pruskich po 1815 r. Tekst stanowi studium postrzegania ziem polskich przez Berlin z perspektywy politycznej i militarnej, jak również potwierdza dostrzeganie za granicą negatywnych aspektów polityki uprawianej przez wielkiego księcia Konstantego.
La influencia de Santa Teresa de Jesús en el teatro español contemporáneo: escritura, confesión y delirio subversivo.
Authors: Blasco Mena M.ª Dolores
Published: December 2022

Santa Teresa de Ávila (1515-1582) patrona de los escritores, mostró desde temprana edad una gran facilidad para la fabulación y para la persuasión, así como un gran deseo de ser la protagonista de su propia vida en un tiempo en el que las mujeres solo podían optar a roles secundarios. En el presente artículo se indaga en la vida y obra de esta escritora, así como en la influencia que su figura tiene en la literatura contemporánea, fundamentalmente en el teatro español. La belleza con que Teresa de Cepeda narrará sus encuentros con el Amado, no sólo será motivo de inspiración para múltiples artistas dentro y fuera de la escena, sino que, además, logrará cambiar la realidad religiosa de su momento y la convertirán en la lideresa de una nueva orden, las carmelitas descalzas, en una época en la que el catolicismo poseía un gran poder político y económico.
Tragedia, humor y feminismo en la dramaturgia de Diana M. De Paco.
Authors: Rodríguez Alonso M.ª Ángeles
Published: December 2022

Diana M. de Paco constituye una de las voces más representativas de la dramaturgia femenina del siglo XXI. El presente trabajo, anclado en el horizonte de los estudios de género, analiza las estrategias dramáticas específicas de la autora, que resultan claves en la construcción de un discurso en femenino. En las páginas que siguen exploramos el modo en que la dramaturga acomoda elementos a priori tan distantes como el humor y la tragedia en la conformación de una poética personal. El análisis detenido y sistemático de ocho de sus textos teatrales —que van desde Polifonía, publicada en 2001, al más reciente que ve la luz en la editorial Irreverentes en 2016— revela la existencia de procedimientos dramatúrgicos comunes que acrisolan y tejen una poética madura y definida especialmente eficaz en la expresión —y la denuncia— de discursos femeninos preteridos y silenciados.
‘Robins’ enseña el español a niños y niñas sordos
Authors: Perdomo Charry Óscar Julián , Bernal Hernán , Orjuela Álvaro David , Cadavid Espinha Sara , Müller Oliver , Aguía-Rojas Karen , Leal Villamizar Lina María
Published: December 2022

Un grupo interdisciplinario de Ingeniería y Ciencias de la Salud de la Universidad del Rosario creó el primer dispositivo interactivo para apoyar a los menores de edad en situación de discapacidad auditiva durante el proceso de aprendizaje de lectoescritura, a través de la lúdica. Está casi listo y se espera que sea de fácil acceso para la población objetivo.
“Somos víctimas, no culpables”: repensando la problemática habitacional española a partir de la experiencia de la Plataforma de Afectados por la Hipoteca de Madrid
Authors: Girado Agustina
Published: December 2022

En el presente trabajo se propone indagar sobre las particularidades que asume la problemática habitacional española, haciendo hincapié en la experiencia de lucha y de trabajo de la Plataforma de Afectados por la Hipoteca. A partir de una estancia de investigación desarrollada en la ciu­dad de Madrid, se abordará la centralidad que asume la plataforma para tensionar la narrativa hegemónica respecto a la crisis de vivienda y habilitar procesos colectivos para que las personas que participan puedan dejar de culpabilizarse, concibiéndose como víctimas. De este modo, interesa analizar las formas en que se moviliza dicha categoría en la reivindicación del derecho a una vivienda y en la generación de un compromiso político con demandas habitacionales que se inscriben en la escena pública.
Transcatheter Closure of Patent Ductus Arteriosus in infants between 2-10 kg
Authors: KAVURT Ahmet Vedat , SAYIN Seçil , ÖZELCE Bilal , BAĞRUL Denizhan , GÜRSU Alper , ECE İbrahim , ÇETİN İbrahim İlker
Published: December 2022

Objective: The aim of this study was to present our experiences on transcatheter patent ductus arteriosus (PDA) closure with different devices, mostly the Amplatzer Piccolo Occluder, in infants weighing between 2-10 kg.
Material and Methods: In this study, the files of 31 patients who underwent transcatheter PDA closure between December 2019 and August 2022 were reviewed retrospectively.
Results: Transcatheter PDA closure was performed on 31(14 female) infants weighing between 2-10 kg. The mean age of patients was 10.7±6.7 months (2-28), and the mean weight was 6.6±2 kg (3-9.9). The median narrowest diameter of the ductus was 2.2 mm (IQR 2-3) and the median ductus length was 6 mm (IQR 4.75-8). The procedural success rate of all interventional procedures was 88% (30 of 34). Complications occurred in a total of four patients including failure of device implantation in one patient, post-procedural device embolization in 2 patients, and the significant residual shunt in one patient. None of the patients required surgery. In 34 interventional procedures, 3 of which were reintervention, 34 devices were used. Twenty-seven (79%) of them were Amplatzer Piccolo Occluder. The median fluoroscopy and procedural times were 10.5 minutes (IQR 7.25-18.5) and 40 minutes (IQR 35-57.5) respectively. The mean duration of follow-up was 10.3±8.8 months (1-32 months).
Conclusion: In our experience, transcatheter treatment of PDA with the Amplatzer Piccolo Occluder device which was our first choice for appropriate duct anatomy and size in infants weighing between 2-10 kg, is safe and effective.