bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electrostatic anti-CD33-antibody–protamine nanocarriers as platform for a targeted treatment of acute myeloid leukemia
Authors: Bäumer Nicole , Scheller Annika , Wittmann Lisa , Faust Andreas , Apel Mara , Nimmagadda Subbaiah Chary , Geyer Christiane , Grunert Katharina , Kellmann Neele , Peipp Matthias , Kailayangiri Sareetha , Gutierrez Suburu Matias Ezequiel , Strassert Cristian A. , Schenk Mathias , Greune Lilo , Rüter Christian , Dersch Petra , Hartmann Wolfgang , Rossig Claudia , Neri Dario , Müller-Tidow Carsten , Schwöppe Christian , Schliemann Christoph , Khandanpour Cyrus , Lenz Georg , Berdel Wolfgang E. , Bäumer Sebastian 
Published: December 2022

Abstract
Background
Acute myeloid leukemia (AML) is a fatal clonal hematopoietic malignancy, which results from the accumulation of several genetic aberrations in myeloid progenitor cells, with a worldwide 5-year survival prognosis of about 30%. Therefore, the development of more effective therapeutics with novel mode of action is urgently demanded. One common mutated gene in the AML is the DNA-methyltransferase DNMT3A whose function in the development and maintenance of AML is still unclear. To specifically target “undruggable” oncogenes, we initially invented an RNAi-based targeted therapy option that uses the internalization capacity of a colorectal cancer specific anti-EGFR-antibody bound to cationic protamine and the anionic siRNA. Here, we present a new experimental platform technology of molecular oncogene targeting in AML.

Methods
Our AML-targeting system consists of an internalizing anti-CD33-antibody–protamine conjugate, which together with anionic molecules such as siRNA or ibrutinib-Cy3.5 and cationic free protamine spontaneously assembles into vesicular nanocarriers in aqueous solution. These nanocarriers were analyzed concerning their physical properties and relevant characteristics in vitro in cell lines and in vivo in xenograft tumor models and patient-derived xenograft leukemia models with the aim to prepare them for translation into clinical application.

Results
The nanocarriers formed depend on a balanced electrostatic combination of the positively charged cationic protamine-conjugated anti-CD33 antibody, unbound cationic protamine and the anionic cargo. This nanocarrier transports its cargo safely into the AML target cells and has therapeutic activity against AML in vitro and in vivo. siRNAs directed specifically against two common mutated genes in the AML, the DNA-methyltransferase DNMT3A and FLT3-ITD lead to a reduction of clonal growth in vitro in AML cell lines and inhibit tumor growth in vivo in xenotransplanted cell lines. Moreover, oncogene knockdown of DNMT3A leads to increased survival of mice carrying leukemia patient-derived xenografts. Furthermore, an anionic derivative of the approved Bruton’s kinase (BTK) inhibitor ibrutinib, ibrutinib-Cy3.5, is also transported by this nanocarrier into AML cells and decreases colony formation.

Conclusions
We report important results toward innovative personalized, targeted treatment options via electrostatic nanocarrier therapy in AML.
Sleep to Reduce Incident Depression Effectively (STRIDE): study protocol for a randomized controlled trial comparing stepped-care cognitive-behavioral therapy for insomnia versus sleep education control to prevent major depression
Authors: Drake Christopher L. , Kalmbach David A. , Cheng Philip , Ahmedani Brian K. , Peterson Edward L. , Joseph Christine L. M. , Roth Thomas , Kidwell Kelley M. , Sagong Chaewon 
Published: December 2022

Abstract
Background
Prevention of major depressive disorder (MDD) is a public health priority. Strategies targeting individuals at elevated risk for MDD may guide effective preventive care. Insomnia is a reliable precursor to depression, preceding half of all incident and relapse cases. Thus, insomnia may serve as a useful entry point for preventing MDD. Cognitive-behavioral therapy for insomnia (CBT-I) is recommended as the first-line treatment for insomnia, but widespread implementation is limited by a shortage of trained specialists. Innovative stepped-care approaches rooted in primary care can increase access to CBT-I and reduce rates of MDD.

Methods/design
We propose a large-scale stepped-care clinical trial in the primary care setting that utilizes a sequential, multiple assignment, randomized trial (SMART) design to determine the effectiveness of dCBT-I alone and in combination with clinician-led CBT-I for insomnia and the prevention of MDD incidence and relapse. Specifically, our care model uses digital CBT-I (dCBT-I) as a first-line intervention to increase care access and reduce the need for specialist resources. Our proposal also adds clinician-led CBT-I for patients who do not remit with first-line intervention and need a more personalized approach from specialty care. We will evaluate negative repetitive thinking as a potential treatment mechanism by which dCBT-I and CBT-I benefit insomnia and depression outcomes.

Discussion
This project will test a highly scalable model of sleep care in a large primary care system to determine the potential for wide dissemination and implementation to address the high volume of population need for safe and effective insomnia treatment and associated prevention of depression.

Trial registration
ClinicalTrials.gov NCT03322774. Registered on October 26, 2017
Condyloma acuminatum of the urinary bladder with underlying squamous cell carcinoma: a case report
Authors: Whitaker John A. 
Published: December 2022

Abstract
Background
Condyloma acuminatum is a rare finding of the urinary bladder. There are many morphological variants that exist. It has been previously reported that some of these variants were found to be associated with subsequent or concurrent squamous cell carcinoma. However, there are limited cases that describe this underlying malignancy found in patients with bladder condyloma.

Case presentation
A 38-year-old African American female presented with condyloma acuminatum of the urinary bladder and underlying squamous cell carcinoma, which also invaded the neighboring uterus, urethra, and anterior vagina. Initial attempts at treatment began with cystoscopic resection of the condyloma; however, due to diffuse transformation, we pursued radical cystectomy with adjuvant chemotherapy and radiation.

Conclusion
As such a finding is rare in the urinary bladder, with few reports discussing its association with ensuing squamous cell carcinoma, we hope that this continues to generate awareness and consideration in the treatment of affected individuals.
Evaluation of factors affecting epidermal growth factor receptor tyrosine kinase inhibitor-induced hepatotoxicity in Japanese patients with non-small cell lung cancer: a two-center retrospective study
Authors: Nagai Hirofumi , Shimada Tsutomu , Takahashi Yoshimitsu , Nishikawa Mikako , Tozuka Hiroyuki , Yamamoto Yasuto , Niwa Osamu , Takahara Yutaka , Fujita Arimi , Nagase Katsuhiko , Kasahara Kazuo , Yano Seiji , Sai Yoshimichi 
Published: December 2022

Abstract
Background
Gefitinib and erlotinib, are epidermal growth factor receptor tyrosine kinase inhibitors, and are currently recommended for non-small cell lung cancer stage IV in the elderly and in patients with decreased performance status in the Japanese Lung Cancer Society Guideline, but they occasionally caused severe hepatotoxicity requiring postponement or modification of treatment. However, little is known about the risk factors for hepatotoxicity in patients receiving gefitinib and erlotinib. In this study, we investigated the factors influencing hepatotoxicity in Japanese non-small cell lung cancer (NSCLC) patients treated with gefitinib or erlotinib monotherapy.

Methods
Japanese patients with NSCLC who started gefitinib or erlotinib monotherapy from January 2005 to December 2017 at Kanazawa University Hospital or Kanazawa Medical University Hospital were included in this study. Factors affecting hepatotoxicity were retrospectively investigated by multiple logistic regression analysis.

Results
A total of 102 patients who received gefitinib and 95 patients who received erlotinib were included in the analysis. In the gefitinib group, a body mass index (BMI) ≥ 25 was associated with an increased risk of hepatotoxicity (OR = 4.571, 95% CI = 1.486–14.056, P = 0.008). In the erlotinib group, concomitant use of acid-suppressing medications (AS), namely proton pump inhibitors or histamine-2 receptor antagonists, was associated with a reduced risk of hepatotoxicity (OR = 0.341, 95% CI = 0.129–0.900, P = 0.030).

Conclusions
BMI ≥ 25 in patients treated with gefitinib increased the risk of hepatotoxicity. In contrast, AS combination with erlotinib reduced the risk of hepatotoxicity. Thus, because different factors influence the risk of hepatotoxicity, monitoring for adverse events should take into account patient background factors and concomitant medications.
Cytokines and cytokine receptors as targets of immune-mediated inflammatory diseases—RA as a role model
Authors: Takeuchi Tsutomu 
Published: December 2022

AbstractRecent advances in our understanding in the immune-mediated inflammatory diseases (IMID) are explored and promoted by the targeted treatment. Among these targets, cytokines and cytokine receptors have become the good candidates for the drug development. In this review, the cytokine and cytokine receptors, which are approved in IMID, are overviewed, and modalities of the treatment, the role of cytokines and cytokine receptors in each disease, and the updated molecular information by modern technologies in rheumatoid arthritis as a role model are shown and discussed for the future perspectives.
Health literacy of pregnant women attending antenatal care clinics in Mansoura district, Egypt
Authors: Essam Noha , Khafagy Mohamad Azmy , Alemam Doaa Shokry 
Published: December 2022

Abstract
Background
Health literacy (HL) is an important maternal factor that is involved in the engagement of a mother and her children with health promotion and preventive activities. Studies have found poor HL in large proportions of the population of both developed and developing countries. This study measures the HL of pregnant women and explores its associated factors.

Methods
A cross-sectional study was conducted on 382 pregnant women attending antenatal care clinics in Mansoura district, Egypt, using an interviewer-administered questionnaire. The Arabic version of the European Health Literacy Survey Questionnaire-short version (HLS-EU-Q16) was used to assess the HL of the participants.

Results
The study showed that 79.8% of studied pregnant women had limited HL (34.5% insufficient HL and 45.3% problematic HL), and only 20.2% of them had sufficient HL. Limited HL was independently predicted by unsatisfactory income (OR = 6.9; 95% confidence interval [CI]: 3.2–15.3; P ≤ 0.05), lower than university education (OR = 5.3; 95% CI: 1.6–17.2; P ≤ 0.05), and having unplanned pregnancy (OR = 3.7; 95% CI: 1.6–8.5; P ≤ 0.05).

Conclusion
The majority of pregnant women in this study had limited HL. It was more frequent among women with lower levels of education, insufficient incomes, and unplanned pregnancies. Antenatal care programs should provide services that respond to the HL level and needs of pregnant women.
Characterization of the Illumina EPIC array for optimal applications in epigenetic research targeting diverse human populations
Authors: Zhang Zhou , Zeng Chang , Zhang Wei 
Published: December 2022

AbstractThe Illumina EPIC array is widely used for high-throughput profiling of DNA cytosine modifications in human samples, covering more than 850,000 modification sites across various genomic features. The application of this platform is expected to provide novel insights into the epigenetic contribution to human complex traits and diseases. Considering the diverse inter-population genetic and epigenetic variation, it will benefit the research community with a comprehensive characterization of this platform for its applicability to major global populations. Specifically, we mapped 866,836 CpG probes from the EPIC array to the human genome reference. We detected 91,034 CpG probes that did not align reliably to the human genome reference. In addition, 21,256 CpG probes were found to ambiguously map to multiple loci in the human genome, and 448 probes showing inaccurate genomic information from the original Illumina annotations. We further characterized those uniquely mapped CpG probes in terms of whether they contained common genetic variants, i.e., single nucleotide polymorphisms (SNPs), in major global populations, by utilizing the 1000 Genomes Project data. A list of optimal CpG probes on the EPIC array was generated for major global populations, with the aim of providing a resource to facilitate future studies of diverse human populations. In conclusion, our analysis indicated that studies of diverse human populations using the EPIC array would be benefited by taking into account of the technical features of this platform.
Non-suicidal self-injury and emotional burden among university students during the COVID-19 pandemic: cross-sectional online survey
Authors: Schleicher Daniel , Heidingsfelder Elisa , Kandsperger Stephanie , Jarvers Irina , Ecker Angelika , Brunner Romuald 
Published: December 2022

SummaryOwing to restrictions of the COVID-19 pandemic, increased stress is evident in university students with a lifetime history of non-suicidal self-injury (NSSI). Therefore, we examined two groups of university students (n= 174) in an online survey, one that exhibited early NSSI in adolescence (n= 51) and another that exhibited continuous NSSI beyond the age of 18 (n= 123) (German Clinical Trials Register DRKS00023731). We compared the two groups in terms of depressive symptoms in the previous 2 weeks as well as self-perceived changes in emotional burden, urge to self-injure and NSSI frequency in the first year of the pandemic compared with the year before (pre-pandemic). Among other findings, both groups showed an increase in emotional burden and urge to self-injure.
Racial and Ethnic Disparities in Cervical Cancer Incidence, Survival, and Mortality by Histologic Subtype
Authors: Cohen Camryn M. , Wentzensen Nicolas , Castle Philip E. , Schiffman Mark , Zuna Rosemary , Arend Rebecca C. , Clarke Megan A. 
Published: December 2022

PURPOSE We conducted an integrated population-based analysis of histologic subtype–specific cervical cancer incidence, survival, and incidence-based mortality by race and ethnicity, with correction for hysterectomy prevalence. METHODS Using the SEER 21 and 18 registries, we selected primary cases of malignant cervical cancer diagnosed among women ≥ 15 years. We evaluated age-adjusted incidence rates among cases diagnosed between 2000 and 2018 (SEER21) and incidence-based mortality rates among deaths from 2005 to 2018 (SEER18), per 100,000 person-years. Rates were stratified by histologic subtype and race/ethnicity (incidence and mortality), and stage, age at diagnosis, and county-level measures of social determinants of health (incidence only). Incidence and mortality rates were corrected for hysterectomy using data from the Behavioral Risk Factor Surveillance System. We estimated 5-year relative survival by histologic subtype and stratified by stage at diagnosis. RESULTS Incidence rates of cervical squamous cell carcinoma were highest in Black and Hispanic women, while incidence rates of cervical adenocarcinoma (ADC) were highest among Hispanic and White women, particularly for localized ADC. County-level income and education variables were inversely associated with squamous cell carcinoma incidence rates in all racial and ethnic groups but had less influence on ADC incidence rates. Black women had the highest overall mortality rates and lowest 5-year relative survival, irrespective of subtype and stage. Disparities in survival were particularly pronounced for Black women with regional and distant ADC, compared with other racial/ethnic groups. CONCLUSION Although Black women are less likely to be diagnosed with ADC compared with all other racial/ethnic groups, they experience the highest mortality rates for this subtype, likely attributed to the poor survival observed for Black women with regional and distant ADC.
Comparison of different ratios of cefoperazone/sulbactam in patients with pyelonephritis
Authors: Jiang Weizhong , Cai Lili 
Published: December 2022

Objective: To compare the clinical efficacy of different ratios of cefoperazone/sulbactam in the treatment of patients with pyelonephritis.
Methods: In this retrospective study clinical records of patients with pyelonephritis treated in Huzhou Traditional Chinese Medicine Hospital from July 2020 to July 2021 were collected. It included 55 patients who received cefoperazone/sulbactam 2:1 treatment (Control group) and 57 patients who received 1 cefoperazone/sulbactam 1:1 treatment (Observation group). Clinical response, inflammatory reaction and bacterial clearance were compared between the two groups.
Results: The levels of C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-8 (IL-8) and leukocyte count (WBC) in the observation group were lower than those in the control group (P<0.05). The total efficacy of the Observation-group was 92.98%, higher than 80.00% of the control group (P<0.05). Fifty-eight strains of bacteria were isolated from the Control-group and 59 strains from the Observation-group. The bacterial clearance rates were 65.52% (38/58) and 83.05% (49/59), respectively. The differences were statistically significant (P<0.05).
Conclusions: The clinical efficacy of 1:1 ratio of cefoperazone/sulbactam in the treatment of patients with pyelonephritis was superior that of 2:1 ratio. This ratio allows to fully utilize the antibacterial effect of cefoperazone, with a significant decrease in inflammation markers and an improvement in bacterial clearance.
doi: https://doi.org/10.12669/pjms.39.1.6850
How to cite this: Jiang W, Cai L. Comparison of different ratios of cefoperazone/sulbactam in patients with pyelonephritis. Pak J Med Sci. 2023;39(1):55-59. doi: https://doi.org/10.12669/pjms.39.1.6850
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
The adverse effects of long-term exposure to antipsychotics among older people with intellectual disabilities: a scoping review
Authors: Turner Jemima , Barry Aisling , Doyle Jack , Hogg Jane , Hynes Alanna , Mahon Emma , Moloney Cora , Shortt Emma , O’Dwyer Máire 
Published: December 2022

Background Antipsychotics are among the medications most prescribed to older adults with intellectual disabilities despite limited evidence to support their safety and efficacy in this population. Antipsychotics are associated with a significant burden of long-term adverse effects including movement disorders, metabolic and cardiovascular adverse effects, sedation and anticholinergic effects. This scoping review aims to evaluate the current extent of the literature relating to adverse effects of long-term antipsychotic use in older adults with intellectual disabilities and identify any existing gaps. Methods The review was conducted in line with the framework for scoping reviews proposed by Arksey and O’Malley. A systematic literature search was carried out, including searches of PubMed, Cochrane Library, ScienceDirect, Embase, PsycINFO and grey literature databases. Reference lists of studies were also reviewed as part of the search. Studies were included in the review if they related to adults over 40 years of age with an intellectual disability who had been taking antipsychotic medication for at least 3 months. Results A total of 13 studies were identified for inclusion in the review. These included retrospective reviews,observational studies, case reports, cohort studies and cross-sectional studies. Adverse effects reported include extrapyramidal symptoms, cardiovascular and metabolic effects, and case reports of rhinorrhoea, hypothermia and ischaemic colitis. Increasing age was associated with a greater burden of adverse effects in some studies. Conclusion The available evidence on the adverse effects of long-term antipsychotic use in older adults with intellectual disabilities is weak and conflicting. The studies included were generally of poor quality with numerous limitations including small sample sizes and lack of control groups. More research is needed to inform understanding of adverse effects associated with long-term antipsychotic use in this population.
Predicting perineal trauma during childbirth using data from a general obstetric population
Authors: Maher Gillian M. , O'Byrne Laura J. , McKernan Joye , Corcoran Paul , Greene Richard A. , Khashan Ali S. , McCarthy Fergus P. 
Published: December 2022

Background: Perineal trauma is a common complication of childbirth and can have serious impacts on long-term health. Few studies have examined the combined effect of multiple risk factors. We developed and internally validated a risk prediction model to predict third and fourth degree perineal tears using data from a general obstetric population. Methods: Risk prediction model using data from all singleton vaginal deliveries at Cork University Maternity Hospital (CUMH), Ireland during 2019 and 2020. Third/fourth degree tears were diagnosed by an obstetrician or midwife at time of birth and defined as tears that extended into the anal sphincter complex or involved both the anal sphincter complex and anorectal mucosa. We used univariable and multivariable logistic regression with backward stepwise selection to develop the models. Candidate predictors included infant sex, maternal age, maternal body mass index, parity, mode of delivery, birthweight, post-term delivery, induction of labour and public/private antenatal care. We used the receiver operating characteristic (ROC) curve C-statistic to assess discrimination, and bootstrapping techniques were used to assess internal validation. Results: Of 8,403 singleton vaginal deliveries, 8,367 (99.54%) had complete data on predictors for model development. A total of 128 women (1.53%) had a third/fourth degree tear. Three variables remained in the final model: nulliparity, mode of delivery (specifically forceps delivery or ventouse delivery) and increasing birthweight (per 100 gram increase) (C-statistic: 0.75, 95% CI: 0.71, 0.79). We developed a nomogram to calculate individualised risk of third/fourth degree tears using these predictors. Bootstrapping indicated good internal performance. Conclusions: Use of our nomogram can provide an individualised risk assessment of third/fourth degree tears and potentially aid counselling of women on their potential risk.
ONLINE STATISTICS SYSTEM FOR PARTICIPANTS IN THE DISCORD MESSENGER USING PYTHON AND POSTGRESQL
Authors: Krapivin Roman R. , Akhmetov Linar M. , Khamidullin Marat R. , Gareeva Gulnara A. 
Published: December 2022

The relevance of the topic under consideration is since in one of the Discord channel communities there was a need to collect the activity of channel members for a certain time and duration.
To solve this problem, it was decided to develop a database and a special bot to interact with this database and the Discord API to collect information.
The goal: development of a system for analyzing, collecting, and displaying information on the activity of participants, developing a database to store all information.
The method or methodology of the work: the article considers a project for collecting, storing, and displaying information about the activity of participants.
Results: a Python discord bot was developed that keeps statistics on the activity of channel members, a PostgreSQL database was developed that stores data on all participants and their activity.
Scope of the results: the functionality of the bot can be used to manage channel members, highlight the most active and allocate incentives for greater activity