bluuebunny/crossref_metadata_2025_split huggingface dataset:
Icariin synergizes therapeutic effect of dexamethasone on adriamycin-induced nephrotic syndrome
Authors: Lv Juan , Xue Guozhong , Zhang Yunxia , Wang Xinbin , Dai Enlai 
Published: January 2023

Abstract
Background
Glomerular damage is a common clinical indicator of nephrotic syndrome. High-dose hormone treatment often leads to hormone resistance in patients. How to avoid resistance and improve the efficiency of hormone therapy draws much attention to clinicians.

Methods
Adriamycin (ADR) was used to induce nephropathy model in SD rats. The rats were treated with dexamethasone (DEX), icariin (ICA), and DEX + ICA combination therapy. The changes in urinary protein (UP), urea nitrogen (BUN), and serum creatinine (SCR) contents in rats were detected by enzyme-linked immunosorbent assay (ELISA), and the degree of pathological injury and the expression level of podocin were detected by HE staining and immunohistochemistry, to test the success of the model and the therapeutic effects of three different ways. The effect of treatments on podocytes autophagy was evaluated via transfection of mRFP-GFP-LC3 tandem adenovirus in vitro.

Results
The contents of UP, SCR, and BUN were significantly increased, the glomerulus was seriously damaged, and the expression of Nephrosis2 (NPHS2) was significantly decreased in the ADR-induced nephrotic syndrome rat model compared to that of the control group. DEX, ICA, and the DEX + ICA combined treatment significantly alleviated these above changes induced by ADR. The combined treatment of DEX + ICA exhibited better outcome than single treatment. The combined treatment also restored the podocyte autophagy, increased the expression of microtubule-associated protein light-chain 3II (LC3II), and reduced the expression of p62 in vitro. The combined treatment protects podocytes by mediating the PI3K/AKT/mTOR (rapamycin complex) signaling pathway.

Conclusion
ICA enhances the therapeutic effect of DEX on the nephrotic syndrome.
Integrated investigation of the clinical implications and targeted landscape for RNA methylation modifications in hepatocellular carcinoma
Authors: Zhang Jianping , Gao Jie , Hu Mingchao , Xu Shiyu , Cheng Chun , Zheng Wenjie , Zhang Jie 
Published: January 2023

Abstract
Background
RNA methylation (RM) is a crucial post-translational modification (PTM) that directs epigenetic regulation. It mostly consists of N1-methyladenosine (m1A), 5-methylcytosine (m5C), N3-methylcytidine (m3C), N6-methyladenosine (m6A), and 2′-O-methylation (Nm). The “writers” mainly act as intermediaries between these modifications and associated biological processes. However, little is known about the interactions and potential functions of these RM writers in hepatocellular carcinoma (HCC).

Methods
The expression properties and genetic alterations of 38 RM writers were assessed in HCC samples from five bioinformatic datasets. Two patterns associated with RM writers were identified using consensus clustering. Then, utilizing differentially expressed genes (DEGs) from different RM subtypes, we built a risk model called RM_Score. Additionally, we investigated the correlation of RM_Score with clinical characteristics, tumor microenvironment (TME) infiltration, molecular subtypes, therapeutic response, immunotherapy effectiveness, and competing endogenous RNA (ceRNA) network.

Results
RM writers were correlated with TME cell infiltration and prognosis. Cluster_1/2 and gene.cluster_A/B were shown to be capable of distinguishing the HCC patients with poor prognosis after consensus and unsupervised clustering of RNA methylation writers. Additionally, we constructed RNA modification pattern-specific risk model and subdivided the cases into RM_Score high and RM_Score low subgroups. In individual cohorts or merged datasets, the high RM_Score was related to a worse overall survival of HCC patients. RM_Score also exhibited correlations with immune and proliferation related pathways. In response to anti-cancer treatments, the RM_Score had a negative correlation (drug sensitive) with drugs that focused on the MAPK/ERK and metabolism signaling, and a positive correlation (drug resistant) with compounds targeting RKT and PI3K/mTOR signaling pathway. Notably, the RM_Score was connected to the therapeutic effectiveness of PD-L1 blockage, implying that RM writers may be the target of immunotherapy to optimize clinical outcomes. Additionally, a ceRNA network was generated including 2 lncRNAs, 4 miRNAs, and 7 mRNAs that was connected to RM writers.

Conclusions
We thoroughly investigated the potential functions of RNA methylation writers and established an RM_patterns-based risk model for HCC patients. This study emphasized the critical functions of RM modification in TME infiltration, targeted therapy, and immunotherapy, providing potential targets for HCC.
Reflective practice and psychotherapy case experience of Specialty Doctors and Associate Specialists (SAS) working in psychiatry: UK-wide survey
Authors: Vaida Alina , Awal Masud 
Published: January 2023

Aims and methodTo survey nationwide opportunities for Balint-type and reflective support group participation and psychotherapy training among doctors classified as Specialty Doctors and Associate Specialists in psychiatry (‘SAS psychiatrists’) and the professional benefits and barriers to access.ResultsApproximately 9% of SAS psychiatrists responded, from all UK regions. A minority reported participating in a Balint-type group (27.3%) or reflective practice/support group (30.9%), and only 6.5% were not interested in participating. Although 44.8% planned to see a psychotherapy case, most reported barriers, particularly time constraints, job plans and lack of support. The 22.1% who reported already gaining psychotherapy case experience reported many benefits, including becoming a better listener (84.8%), more empathetic (81.2%), enjoying work more (78.8%) and overall becoming a better psychiatrist (90.9%).Clinical implicationsThe reported interest in Balint group and psychotherapy training opportunities exceeded existing provision; psychotherapy case experience benefited professional development and self-reported clinical capabilities. Healthcare trusts and boards need to consider more actively supporting SAS psychotherapy training and reflective practice.
National Cancer Grid Virtual Tumor Boards of Head and Neck Cancers: An Innovative Approach to Multidisciplinary Care
Authors: Thiagarajan Shivakumar , Poojari Vinisha , Tuljapurkar Vidisha , Ghosh-Laskar Sarbani , Fatehi Khuzema , Babu Sajith , Penumadu Prashant , Patil Asawari , Joshi Amit , Kumar Suman , Chaukar Devendra , Kannan Ravi , Pramesh C.S. 
Published: January 2023

PURPOSEVirtual tumor board (VTB) via videoconference facility involving multiple specialists in the decision making for various tumors is well accepted, especially in high-income countries. Information on virtual tumor boards for head and neck cancers especially from low- and middle-income countries is sparse. In this study, we have audited the findings of the National Cancer Grid VTBs performed for head and neck cancers.METHODSAll patients discussed in the head and neck VTBs at our center between December 2016 and February 2022 were included in the study. Details such as the type of institute sending patients for discussion, its location, subsites within the head and neck region, histopathology, treatment setting or question for the VTB, and availability of guidelines for such patient scenarios were assessed. Also, a survey was sent to assess the usefulness of the VTBs.RESULTSA total of 208 patients were discussed in 54 VTB sessions. The most common head and neck sites discussed in the VTBs were the oral cavity (n = 64, 30.7%) followed by skull base/nose and paranasal sinuses/eyelid-orbit tumors (n = 49, 23.5%). Nonsquamous cell carcinoma was the most common histopathology discussed; recurrent cancers/residual diseases were the most common treatment settings (n = 134, 64.4%) for which there were no existing guidelines. Survey results showed that most VTB decisions were implementable, and respondents felt that VTBs were a useful educational tool as well.CONCLUSIONOur study affirms the feasibility of VTBs in low- and middle-income countries' health care systems for managing uncommon malignancies and clinical situations, which act as an important educational platform.
Phase I Study of Single-Agent Anti–Programmed Death-1 (MDX-1106) in Refractory Solid Tumors: Safety, Clinical Activity, Pharmacodynamics, and Immunologic Correlates
Authors: Brahmer Julie R. , Drake Charles G. , Wollner Ira , Powderly John D. , Picus Joel , Sharfman William H. , Stankevich Elizabeth , Pons Alice , Salay Theresa M. , McMiller Tracee L. , Gilson Marta M. , Wang Changyu , Selby Mark , Taube Janis M. , Anders Robert , Chen Lieping , Korman Alan J. , Pardoll Drew M. , Lowy Israel , Topalian Suzanne L. 
Published: January 2023

Purpose Programmed death-1 (PD-1), an inhibitory receptor expressed on activated T cells, may suppress antitumor immunity. This phase I study sought to determine the safety and tolerability of anti–PD-1 blockade in patients with treatment-refractory solid tumors and to preliminarily assess antitumor activity, pharmacodynamics, and immunologic correlates. Patients and Methods Thirty-nine patients with advanced metastatic melanoma, colorectal cancer (CRC), castrate-resistant prostate cancer, non–small-cell lung cancer (NSCLC), or renal cell carcinoma (RCC) received a single intravenous infusion of anti–PD-1 (MDX-1106) in dose-escalating six-patient cohorts at 0.3, 1, 3, or 10 mg/kg, followed by a 15-patient expansion cohort at 10 mg/kg. Patients with evidence of clinical benefit at 3 months were eligible for repeated therapy. Results Anti–PD-1 was well tolerated: one serious adverse event, inflammatory colitis, was observed in a patient with melanoma who received five doses at 1 mg/kg. One durable complete response (CRC) and two partial responses (PRs; melanoma, RCC) were seen. Two additional patients (melanoma, NSCLC) had significant lesional tumor regressions not meeting PR criteria. The serum half-life of anti–PD-1 was 12 to 20 days. However, pharmacodynamics indicated a sustained mean occupancy of > 70% of PD-1 molecules on circulating T cells ≥ 2 months following infusion, regardless of dose. In nine patients examined, tumor cell surface B7-H1 expression appeared to correlate with the likelihood of response to treatment. Conclusion Blocking the PD-1 immune checkpoint with intermittent antibody dosing is well tolerated and associated with evidence of antitumor activity. Exploration of alternative dosing regimens and combinatorial therapies with vaccines, targeted therapies, and/or other checkpoint inhibitors is warranted.
Ertugliflozin Delays Insulin Initiation and Reduces Insulin Dose Requirements in Patients With Type 2 Diabetes: Analyses From VERTIS CV
Authors: Dagogo-Jack Samuel , Frederich Robert , Liu Jie , Cannon Christopher P , Shi Harry , Cherney David Z I , Cosentino Francesco , Masiukiewicz Urszula , Gantz Ira , Pratley Richard E 
Published: January 2023

Abstract

Context
VERTIS CV evaluated the cardiovascular safety of ertugliflozin in patients with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD).

Objective
The aim of these analyses was to assess the insulin requirements of VERTIS CV patients over the trial duration.

Methods
Patients received ertugliflozin 5 mg, 15 mg, or placebo once daily; mean follow-up was 3.5 years. Time to insulin initiation in patients who were insulin naïve at baseline, change in insulin dose in patients receiving baseline insulin, and hypoglycemia incidence in both patient groups were assessed.

Results
In VERTIS CV, mean duration of type 2 diabetes was 13.0 years; glycated hemoglobin was 8.2%. Among 4348 (53%) insulin-naïve patients, the likelihood of insulin initiation was significantly reduced with ertugliflozin vs placebo (ertugliflozin 5 mg: hazard ratio [HR] 0.70, 95% CI 0.58-0.84; ertugliflozin 15 mg: HR 0.64, 95% CI 0.53-0.78). Time to insulin initiation was delayed with ertugliflozin; the estimated delay in reaching a 10% cumulative incidence of new insulin initiations vs placebo was 399 days with ertugliflozin 5 mg and 669 days with ertugliflozin 15 mg. Among 3898 (47%) patients receiving baseline insulin, the likelihood of requiring a ≥20% increase in insulin dose was significantly reduced with ertugliflozin vs placebo (ertugliflozin 5 mg: HR 0.62, 95% CI 0.52-0.75; ertugliflozin 15 mg: HR 0.51, 95% CI 0.41-0.62). The incidence of hypoglycemia events was not increased with ertugliflozin treatment.

Conclusion
In VERTIS CV patients, ertugliflozin reduced the likelihood of insulin initiation, delayed the time to insulin initiation by up to ∼1.8 years, and reduced insulin dose requirements vs placebo, without increasing hypoglycemia events.
The Effect of Early Time-Restricted Eating vs Later Time-Restricted Eating on Weight Loss and Metabolic Health
Authors: Liu Juanhong , Yi Pan , Liu Feng 
Published: January 2023

Abstract

Context
It remains controversial whether the choice of the daily eating window early or later in time-restricted eating (TRE) intervention (early or later TRE) has different effects on weight loss and metabolic health.

Objective
A network meta-analysis was performed to evaluate the efficacy between early and later TRE in adults with obesity or overweight.

Methods
We searched PubMed, Embase, Web of Science, and Cochrane Library for randomized controlled trials (RCTs) published until October 16, 2022. We conducted a network meta-analysis to evaluate the efficacy of early and later TRE on body weight and metabolic parameters, including glycemic metabolism, blood pressure, and lipid profiles.

Results
Twelve RCTs with 730 obese or overweight adults were included in this meta-analysis. Early TRE and later TRE both elicited moderate reductions in body weight and insulin resistance (IR) (homeostasis model assessment of IR) when compared to non-TRE. Interestingly, early TRE showed more effectiveness than later TRE in improving IR (early vs later TRE: −0.44; 95% CI, −0.86 to −0.02; P &lt; .05), whereas no statistically significant difference was detected in weight loss (early vs later TRE: −0.31 kg; 95% CI, −1.15 to 0.53 kg; P &gt;.05). In addition, early TRE rather than later TRE showed significant benefits in glycemic metabolism and blood pressure when compared to non-TRE. No significant differences between early and later TRE were observed for fasting blood glucose, blood pressure, and lipid profiles.

Conclusion
This meta-analysis suggests that people may choose early TRE for more effective weight management and metabolic benefits. Nevertheless, further large-scale RCTs are warranted to verify our findings.
Mortality as a Function of Survival
Authors: Alvarez Jesús-Adrián , Vaupel James W. 
Published: January 2023

Abstract
Everyone has a chronological age. Because survivorship declines relentlessly in populations with age-specific death rates greater than zero, everyone also has a survivorship age (“s-age”), the age at which a proportion s of the population is still alive. S-ages can be estimated for both periods and cohorts. While trajectories of mortality over chronological ages differ (e.g., across populations, over time, by sex, or by any subpopulation), mortality trajectories over s-ages are similar, a sign that populations experience similar mortality dynamics at specific levels of survivorship. We show that this important demographic regularity holds for 23 sex-specific populations analyzed during a period comprising more than 100 years.
The Role of Suburbanization in Metropolitan Segregation After 1940
Authors: Logan John R. , Kye Samuel , Carlson H. Jacob , Minca Elisabeta , Schleith Daniel 
Published: January 2023

Abstract
The three decades from 1940 through 1970 mark a turning point in the spatial scale of Black–White residential segregation in the United States compared with earlier years. We decompose metropolitan segregation into three components: segregation within the city, within the suburbs, and between the city and its suburbs. We then show that extreme levels of segregation were well established in most cities by 1940, and they changed only modestly by 1970. In this period, changes in segregation were greater at the metropolitan scale, driven by racially selective population growth in the suburbs. We also examine major sources of rising segregation, including region, metropolitan total, and Black population sizes, and indicators of redlining in the central cities based on risk maps prepared by the Home Owners Loan Corporation (HOLC) in the late 1930s. In addition to overall regional differences, segregation between the city and suburbs and within suburbia increased more in metropolitan areas with larger Black populations, but this relationship was found only in the North. In contrast to some recent theorizing, there is no association between preparation of an HOLC risk map or the share of city neighborhoods that were redlined and subsequent change in any component of segregation.
Investigation of mutational spectrum in cytochrome P4501B1 (CYP1B1) as the principal cause of primary congenital glaucoma
Authors: Zahid Tazeen , Khan Dr. Muhammad Umer , Zulfiqar Aymn , Jawad Fatima , Saleem Anosh , Khan Ahmad Raza 
Published: January 2023

Objective: To identify the genetic variants in the CYP1B1 gene associated with Primary Congenital Glaucoma (PCG) and to predict its pathological effect.
Method: A descriptive study was conducted in the time period of nine months (September 2021-May 2022) after the ethical approval was taken from The Children Hospital and Institute of Child Health (CH & ICH). Two milliliters of the blood sample from PCG-affected individuals were collected in EDTA vacutainers and genomic DNA was extracted by a phenol-chloroform method. The semi-quantification of extracted DNA was done by agarose gel electrophoresis. PCR amplification was performed by specific primers of CYP1B1 gene then termination sequencing (di-deoxy) was done to detect the genetic variants. Different bioinformatics tools such as BLAST, Ensembl, Clustal Omega, Polyphen and SIFT were used for the further analysis of mutation causing the disease.
Results: A total of 85% of patients were bilaterally affected, while 15% were unilaterally affected. Mutation analysis identified five non related known variants. Two missense mutations (c.355 G/T p.A119S and c.685G/A p.E229K) occurred in 94% patients and intragenic SNP occurred in 29% patients along with the 1% somatic (c.693C/A p.F231L) and stop gained mutation (c.840C/A p.C280*).
Conclusion: Genetic analysis in the current study showed that 85% of PCG affected patients were due to the CYP1B1 mutation, and disease heterogeneity might be reduced through genetic counseling.
doi: https://doi.org/10.12669/pjms.39.2.7081
How to cite this: Zahid T, Khan MU, Zulfiqar A, Jawad F, Saleem A, Khan AR. Investigation of mutational spectrum in cytochrome P4501B1 (CYP1B1) as the principal cause of primary congenital glaucoma. Pak J Med Sci. 2023;39(2):---------. doi: https://doi.org/10.12669/pjms.39.2.7081
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.
Technological innovation for workload allocation in nursing care management: an integrative review
Authors: Galiano Maria Alejandra , Moreno Fergusson Maria Elisa , Guerrero William J. , Muñóz Maria Francisca , Ortiz Basto Germán A. , Cardenas Ramírez Juan Sebastián , Guevara Lozano Maryory , Larraín Sundt Ana 
Published: January 2023

Background: Technology reduces the nursing workload, improve the quality care processes, patient's safety, and avoid staff burnout. Innovative technologies are disrupting healthcare systems by improving the efficiency of processes and management. There is a discussion on the benefits, challenges, and barriers of these technologies and considering human factors of nursing management. Methods: To analyse the nursing workload models, the predictors of nursing burnout and outcomes, the new technologies and its acceptance for nursing care management based on the literature. An integrative literature review is performed. Scopus, Scielo, PUBMED, and CINALH databases were searched to perform an integrative review following PRISMA guidelines. Articles published from January 2016 to December 2020 were included. Quality appraisal was performed using the Crowe Critical Appraisal Tool version 1.4 (CCAT). Two reviewers independently examined the title and abstract for eligibility according to the inclusion and exclusion criteria. Quality appraisal was performed using the Crowe Critical Appraisal Tool version 1.4 (CCAT). Results: Initially 2,818 articles were potentially relevant. After following the PRISMA Guidelines, 35 studies were included in the review. Four themes appeared: Nursing workload models; Predictors of nursing burnout and outcomes; Information technologies and technological means for management; Technology acceptance. Conclusions: Technology has the potential to improve care management by estimating nurse workload in ICUs and non-critical units, but scientific evidence is more detailed in the former type of services. The literature provides insights about the factors that factors and the barriers that promote the technology acceptance and usability. We did not find studies comparing technologies and no scientific evidence proving improvements in care.
Pre-exposure to azithromycin enhances gonococcal resilience to subsequent ciprofloxacin exposure: an in vitro study
Authors: González Natalia , Elise Laumen Jolein Gyonne , Abdellati Saïd , de Block Tessa , De Baetselier Irith , Van Dijck Christophe , Kenyon Chris , S. Manoharan–Basil Sheeba 
Published: January 2023

Background: The effect of sequential exposure to different antibiotics is an underexplored topic. Azithromycin can be detected in humans for up to 28 days post-ingestion and may prime bacterial responses to subsequently ingested antibiotics. Methods: In this in vitro study, we assessed if preexposure to azithromycin could accelerate the acquisition of resistance to ciprofloxacin in Neisseria gonorrhoeae reference strain, WHO–F. In a morbidostat, we set two conditions in 3 vials each: mono-exposure (preexposure to Gonococcal Broth followed by exposure to ciprofloxacin) and dual sequential exposure (preexposure to azithromycin followed by exposure to ciprofloxacin).The growth of the cultures was measured by a software (MATLAB). The program decided if gonococcal broth or antibiotics were added to the vials in order to keep the evolution of the cultures. Samples were taken twice a week until the end of the experiment i.e. until resistance was achieved or cellular death. Additionally, six replicates of WHO–F WT and WHO–F with rplV mutation, caused by azithromycin, were exposed to increasing concentrations of ciprofloxacin in plates to assess if there were differences in the rate of resistance emergence. Results: We found that after 12 hours of pre-exposure to azithromycin, N. gonorrhoeae's resilience to ciprofloxacin exposure increased. Pre-exposure to azithromycin did not, however, accelerate the speed to acquisition of ciprofloxacin resistance. Conclusions: We found that azithromycin does not accelerate the emergence of ciprofloxacin resistance, but there were differences in the molecular pathways to the acquisition of ciprofloxacin resistance: the strains preexpossed to azithromycin followed a different route (GyrA: S91F pathway) than the ones without antibiotic preexposure (GyrA:D95N pathway). However, the number of isolates is too small to draw such strong conclusions.