bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kinase Mutations and Imatinib Response in Patients With Metastatic Gastrointestinal Stromal Tumor
Authors: Heinrich Michael C. , Corless Christopher L. , Demetri George D. , Blanke Charles D. , von Mehren Margaret , Joensuu Heikki , McGreevey Laura S. , Chen Chang-Jie , Van den Abbeele Annick D. , Druker Brian J. , Kiese Beate , Eisenberg Burton , Roberts Peter J. , Singer Samuel , Fletcher Christopher D.M. , Silberman Sandra , Dimitrijevic Sasa , Fletcher Jonathan A. 
Published: October 2023

PURPOSE Most gastrointestinal stromal tumors (GISTs) express constitutively activated mutant isoforms of KIT or kinase platelet-derived growth factor receptor alpha (PDGFRA) that are potential therapeutic targets for imatinib mesylate. The relationship between mutations in these kinases and clinical response to imatinib was examined in a group of patients with advanced GIST. PATIENTS AND METHODS GISTs from 127 patients enrolled onto a phase II clinical study of imatinib were examined for mutations of KIT or PDGFRA. Mutation types were correlated with clinical outcome. RESULTS Activating mutations of KIT or PDGFRA were found in 112 (88.2%) and six (4.7%) GISTs, respectively. Most KIT mutations involved exon 9 (n = 23) or exon 11 (n = 85). All KIT mutant isoforms, but only a subset of PDGFRA mutant isoforms, were sensitive to imatinib, in vitro. In patients with GISTs harboring exon 11 KIT mutations, the partial response rate (PR) was 83.5%, whereas patients with tumors containing an exon 9 KIT mutation or no detectable mutation of KIT or PDGFRA had PR rates of 47.8% ( P = .0006) and 0.0% ( P < .0001), respectively. Patients whose tumors contained exon 11 KIT mutations had a longer event-free and overall survival than those whose tumors expressed either exon 9 KIT mutations or had no detectable kinase mutation. CONCLUSION Activating mutations of KIT or PDGFRA are found in the vast majority of GISTs, and the mutational status of these oncoproteins is predictive of clinical response to imatinib. PDGFRA mutations can explain response and sensitivity to imatinib in some GISTs lacking KIT mutations.
Disparities With Systemic Therapies for Black Men Having Advanced Prostate Cancer: Where Do We Stand?
Authors: Gong Jun , Kim Daniel M. , De Hoedt Amanda M. , Bhowmick Neil , Figlin Robert , Kim Hyung L. , Sandler Howard , Theodorescu Dan , Posadas Edwin , Freedland Stephen J. 
Published: October 2023

PURPOSE Prostate cancer represents the most common cancer diagnosis in Black men and is the second leading cause of cancer death in this population. Multilevel disparities have been well-documented in Black men with prostate cancer and play a role in poorer survival outcomes when compared with White men with prostate cancer. In this review, we highlight the changing trend in disparities for systemic therapy outcomes in Black men diagnosed with metastatic prostate cancer. METHODS We reviewed data from real-world registries and prospective clinical trials with a particular focus on equal access settings to compare outcomes to systemic therapies between Black and White men with metastatic prostate cancer. RESULTS In metastatic prostate cancer, there is growing evidence to suggest that Black men may have similar, if not better, outcomes to systemic therapies than White men with advanced disease, as corroborated by prospective studies and clinical trials where health care delivery and follow-up are more likely to be standardized. CONCLUSION This review illustrates the importance of nonbiological drivers of racial disparities in Black men with advanced prostate cancer. Mitigating barriers to health care access and delivery as well as including participation in clinical trials will be pivotal to ongoing efforts to address disparities in systemic therapy outcomes for Black men with metastatic prostate cancer.
Hyperandrogenism and Cardiometabolic Risk in Pre- and Postmenopausal Women—What Is the Evidence?
Authors: Hirschberg Angelica Lindén 
Published: October 2023

Abstract
Hyperandrogenism in women, such as polycystic ovary syndrome, ovarian hyperthecosis, congenital adrenal hyperplasia, and androgen-secreting tumors, are all associated with increased prevalence of cardiovascular risk factors that include type 2 diabetes, hypertension, dyslipidemia, and metabolic syndrome. However, it is not clear whether this also implies enhanced risk of cardiovascular disease and mortality. Furthermore, the involvement of obesity and menopausal status for cardiometabolic risk in these women has not been elucidated. Based on the most recent systematic reviews and meta-analyses, this review summarizes the latest scientific evidence. To conclude, hyperandrogenism in premenopausal women is associated with enhanced prevalence of cardiovascular risk factors, as well as increased risk of cardiovascular disease and mortality, independently of body mass index. In contrast, elevated cardiovascular risk factors and increased risk of myocardial infarction and stroke in hyperandrogenic postmenopausal women are dependent on obesity. Furthermore, the overall risk of cardiovascular disease and coronary artery disease in hyperandrogenic postmenopausal women is similar to controls. The reason for a reduced cardiometabolic risk after menopause in hyperandrogenic women compared to nonhyperandrogenic women is not clear. It can be speculated that the difference in endocrine balance and metabolic status between women with and without hyperandrogenism might decrease after menopause because hyperandrogenism usually improves with age, whereas menopausal transition itself is associated with androgen dominance and abdominal obesity. Although we have gained increased knowledge about cardiometabolic risks in women with hyperandrogenism, it must be acknowledged that the quality of data is overall low. More research is needed, especially longer and larger follow-up studies in women with hyperandrogenism of different etiologies and phenotypes.
Homeostasis Model Assessment of β-Cell Function for Diagnosis of Insulinoma
Authors: Bódis Kálmán , Schön Martin , Dauben Laura , Wilker Miriam , Strassburger Klaus , Burkart Volker , Roden Michael , Müssig Karsten 
Published: October 2023

Abstract

Context
Diagnosis of insulinoma is based on different criteria from the 72-hour fasting test according to current guidelines (Endocrine Society [ES], European [ENETS], and North American [NANETS] Neuroendocrine Tumor Societies), including assessment of β-cell function by glucagon stimulation test.

Objective
This study tested whether the homeostasis model assessment of insulin secretion, including assessment of β-cell function, (HOMA-B) at the end of the fasting test provides comparable efficacy for insulinoma diagnosis.

Methods
In 104 patients with suspected insulinoma, 72-hour fasting tests were performed with frequent assessment of glucose, insulin, and C-peptide in venous blood. HOMA-B values using insulin and C-peptide were calculated at the end of the fasting test, as defined by the lowest glucose concentration from each participant.

Results
HOMA-B was more than 6.5-fold higher in patients with (n = 23) than in those without (n = 81) insulinoma (insulin and C-peptide; both P &lt; .001). HOMA-B (cutoff using insulin &gt;253 a.u. and C-peptide &gt;270 a.u.) had a sensitivity of 0.96, 0.78 to 1.00, and a specificity of 0.96 or greater (≥0.89-0.99) for insulinoma diagnosis. ES and ENETS/NANETS criteria reached a diagnostic sensitivity of less than or equal to 0.96 (≤0.78-1.00) and ≤0.83 (≤0.61-0.95) as well as specificity of ≤0.85 (≤0.76-0.92) and less than or equal to 1.00 (≤0.96-1.00) for insulin, and C-peptide, respectively. Using insulin for HOMA-B, sensitivity tended to be higher compared to ENETS/NANETS criteria (P = .063) and specificity was higher compared to ES criteria using insulin and C-peptide (both P &lt; .005).

Conclusion
HOMA-B, as calculated at the end of the fasting test employing defined cutoffs for insulin and C-peptide, provides excellent diagnostic efficacy, suggesting that it might represent an alternative and precise tool to diagnose insulinoma.
Interplay between the plasma membrane and cell–cell adhesion maintains epithelial identity for correct polarised cell divisions
Authors: Hosawi Manal M. , Cheng Jiaoqi , Fankhaenel Maria , Przewloka Marcin R. , Elias Salah 
Published: October 2023

ABSTRACT
Polarised epithelial cell divisions represent a fundamental mechanism for tissue maintenance and morphogenesis. Morphological and mechanical changes in the plasma membrane influence the organisation and crosstalk of microtubules and actin at the cell cortex, thereby regulating the mitotic spindle machinery and chromosome segregation. Yet, the precise mechanisms linking plasma membrane remodelling to cell polarity and cortical cytoskeleton dynamics to ensure accurate execution of mitosis in mammalian epithelial cells remain poorly understood. Here, we manipulated the density of mammary epithelial cells in culture, which led to several mitotic defects. Perturbation of cell–cell adhesion formation impairs the dynamics of the plasma membrane, affecting the shape and size of mitotic cells and resulting in defects in mitotic progression and the generation of daughter cells with aberrant architecture. In these conditions, F- actin–astral microtubule crosstalk is impaired, leading to mitotic spindle misassembly and misorientation, which in turn contributes to chromosome mis-segregation. Mechanistically, we identify S100 Ca2+-binding protein A11 (S100A11) as a key membrane-associated regulator that forms a complex with E-cadherin (CDH1) and the leucine-glycine-asparagine repeat protein LGN (also known as GPSM2) to coordinate plasma membrane remodelling with E-cadherin-mediated cell adhesion and LGN-dependent mitotic spindle machinery. Thus, plasma membrane-mediated maintenance of mammalian epithelial cell identity is crucial for correct execution of polarised cell divisions, genome maintenance and safeguarding tissue integrity.
Metformin versus sodium glucose co-transporters inhibitors as first-line for atherosclerotic cardiovascular disease: A meta-analysis
Authors: Alatawi Amirah M. 
Published: October 2023

There is growing evidence of prescribing sodium glucose co-transporters-2 inhibitor (SGLT-2) to patients with/at high risk of atherosclerotic cardiovascular disease as first-line (instead of metformin). This is the first meta-analysis to compare SGLT-2 inhibitors regarding the same. We aimed to compare SGLT-2 inhibitors and metformin regarding heart failure, acute coronary syndrome, and ischemic stroke. We systematically searched PubMed and Cochrane Library for relevant articles from the first article up to August 2022. The following keywords were used: Metformin, Salt glucose co-transporters inhibitors, SGLT-2 inhibitors, empagliflozin, dapagliflozin, canagliflozin, and first-line. The retrieved data were exported to an excel sheet detailing the author’s names, the country of origin of the study, the number of patients and control subjects, the study duration, and the total number of events in the interventional and exercise groups. Out of 108 articles screened, only three studies fulfilled the inclusion criteria, a databased study, and two cohorts with 10309 events and 86487 patients. The present meta-analysis showed that SGLT-2 inhibitors had lower rates of heart failure (odd ratio, 1.51, 95% CI, 1.10-2.08) and myocardial infarction (odd ratio, 1.45, 95% CI, 1.08-1.96) than metformin with a similar rate of stroke (odd ratio, 1.03, 95% CI, 0.66-1.61). Significant heterogeneity was observed. Sodium-glucose co-transporter inhibitors-2 as first-line therapy showed a lower heart failure and myocardial infarction compared to metformin. No significant difference was found between the two drugs regarding ischemic stroke. Further larger studies comparing the adverse event are needed.
doi: https://doi.org/10.12669/pjms.40.1.6982
How to cite this: Alatawi AM. Metformin versus sodium glucose co-transporters inhibitors as first-line for atherosclerotic cardiovascular disease: A meta-analysis. Pak J Med Sci. 2024;40(1):---------. doi: https://doi.org/10.12669/pjms.40.1.6982
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.
Effects of cognitive behavioral and psychological intervention on social adaptation, psychological resilience and level of hope in patients with nasopharyngeal carcinoma in radiotherapy
Authors: Liu Xiaohui , Wang Ce , Li Yanhong , Wang Yue 
Published: October 2023

Objective: To evaluate the effects of cognitive behavioral and psychological intervention(CBPI) on social adaptation, psychological resilience, and the level of hope in patients with nasopharyngeal carcinoma(NPC) in radiotherapy.
Methods: This is application research. Eighty patients undergoing radiotherapy for NPC at Affiliated Hospital of Hebei University from November 20, 2020 to November 15, 2022 were randomized into control and study groups at a 1:1 ratio. While the control group was provided with standard specialized nursing care, the study group was offered CBPI in addition to the exact nursing care. Differences in quality of life, psychological resilience, level of hope, emotional state, and patient satisfaction between the groups were compared and analyzed before and after treatment.
Results: After an intervention, significantly improved physical, mental, and social functions and material living conditions were observed in the study group compared with the control group (all p< 0.05). Although both groups scored higher on the selected psychological resilience scale following the intervention, the study group showed better results as compared to control group in adaptability, tenacity, control, and goal orientation (all p< 0.05). While both groups had elevated scores of temporality and future, interconnectedness, and positive readiness and expectancy at the end of the intervention, the improvements were more pronounced in the study group (all p< 0.05).
Conclusion: CBPI supports radiotherapy for NPC by improving patients’ quality of life, confidence in treatment, the hope of recovery, psychological resilience, anxiety, depression, and patient satisfaction. Therefore, this treatment strategy is worthy of wide application in clinical settings.
doi: https://doi.org/10.12669/pjms.40.1.7421
How to cite this: Liu X, Wang C, Li Y, Wang Y. Effects of cognitive behavioral and psychological intervention on social adaptation, psychological resilience and level of hope in patients with nasopharyngeal carcinoma in radiotherapy. Pak J Med Sci. 2024;40(1):---------. doi: https://doi.org/10.12669/pjms.40.1.7421
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.
Efficacy of Letrozole vs Clomiphene Citrate for induction of ovulation in women with polycystic ovarian syndrome
Authors: Wasim Tayyiba , Nasrin Tahira , Zunair Javeria , Irshad Sonia 
Published: October 2023

Objective: To compare the efficacy of letrozole vs Clomiphene citrate for ovulation induction in PCOS women.
Methods: This double blind randomized controlled trial was conducted at Services Hospital, Lahore, from January 2016 to December 2020. Total 220 patients, diagnosed with PCOS according to Rotterdam criteria were randomly assigned into two groups after taking informed consent. The women were followed for ovulation, pregnancy and live birth rates in the next five consecutive menstrual cycles with either clomiphene citrate or letrozole.
Results: Letrozole had significantly better pregnancy rate (29.0% vs 15.4% p-value 0.015), monofollicular development (77.2% vs 52.7% p-value 0.000) and live birth rate (25.4% vs 10.9% p-value 0.005) as compared to clomiphene citrate. There was no difference between the two groups in ovulation rate (68.1% vs 63.6%, p-value 0.477), early pregnancy loss (3.6% vs 4.5% p-value 0.734), and twin pregnancy (0.0% vs 1.81% p-value 0.155). There was no ectopic pregnancy and no congenital anomalies in both groups. Hot flushes were higher in clomiphene group (31.8% vs 12.7% p-value 0.001) while fatigue (30.9% vs 8.1% p-value 0.000) and dizziness (21.8% vs 10.0% p-value 0.029) was higher with letrozole but these were well tolerated.
Conclusion: Letrozole is better treatment choice than clomiphene citrate in PCOS women with infertility in terms of pregnancy and live birth rate.
ClinicalTrials.gov Identifier: NCT05702957.
doi: https://doi.org/10.12669/pjms.40.1.7971
How to cite this: Wasim T, Nasrin T, Zunair J, Irshad S. Efficacy of Letrozole vs Clomiphene Citrate for induction of ovulation in women with polycystic ovarian syndrome. Pak J Med Sci. 2024;40(1):---------. doi: https://doi.org/10.12669/pjms.40.1.7971
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.
Rehabilitation of patients with post-traumatic stress disorder by complementary methods
Authors: Chukhraev Nikolay , Zukow Walery , Vladymyrova Nataliya , Fedorov Serhii , Chukhraeva Elena , Unichenko Antonina , Chernyak Viktor 
Published: October 2023

Introduction. The article analyzes the relationship between stress, post-traumatic stress syndrome (PTSD) and changes in the functioning of the neuroendocrine system.
Aim. Development of a hypothesis and practical evaluation of its effectiveness based on the proposed rehabilitation protocols for patients with post-traumatic stress disorder resulting from psychoemotional stress, based on a multi-level multifactorial approach with the use of transcranial stimulation by pulse currents at the frequency of rhythms of the cerebral cortex, stimulation by light pulses at the frequencies of alpha, beta and theta rhythms of the cerebral cortex in combination with neuroacoustic correction of the neuroendocrine system.
Materials and methods. The study involved 36 men, combatants, aged 28-54 full years, who gave their written consent to participate in the study. In the course of the research at the first stage, a hypothesis was formed about possible options for multifactorial multilevel effects on the central nervous system in order to rehabilitate patients with PTSD.
Results. The implementation of the proposed solution is to increase the efficiency and reduce the time of rehabilitation of PTSD due to a multi-level multifactorial approach:
Conclusion. The results of the study revealed positive dynamics of clinical manifestations in both groups of patients. After analyzing the data obtained (assessment of the quality of life according to the SF-36 questionnaire), it was found that the protocol of rehabilitation of patients with post-traumatic stress disorder is based on the use of a multi-level approach that allows correction.
Surface plasmon resonance sensor composed of micro-nano optical fibers for high-sensitivity refractive index detection
Authors: Fu Haihao , Liu Chao , Xu Luhui , Liu Wei , Lv Jingwei , Wang Jianxin , He Jie , Luo Xingdi , Chu Paul K. 
Published: October 2023

Spurred by the continuous development of surface plasmon resonance (SPR) technology, optical fiber sensors based on SPR have become a research hotspot. Although single-mode fibers (SMFs) are simple and easy to manufacture, the sensitivity is quite poor. On the other hand, even though photonic crystal fibers (PCFs) and anti-resonant fibers (ARFs) can achieve high-sensitivity detection and the wavelength sensitivity is tens of times that of SMFs, they are complex and difficult to produce. Herein, an SPR refractive index sensor composed of micro-nano optical fibers (MNFs) is designed to detect analytes in the refractive index range between 1.33 and 1.43. Analysis by the finite element method (FEM) reveals that the maximum wavelength sensitivity is 49,000 nm/RIU. The SPR sensor boasting a simple structure, low cost, and high wavelength sensitivity has enormous potential in applications such as chemical analysis, environmental monitoring, and other fields.
Modified genetic algorithm for inverse design of anti-resonant hollow core fiber with low confinement loss
Authors: Chen Ruifeng , Ye Feng , Wang Zimiao , Huang Jiayao , Li Qian 
Published: October 2023

Low-loss anti-resonant hollow core fibers (AR-HCF) are important for optical communication systems, photonics-enabled sensors, and exploring nonlinear dynamics with gas-light interaction. However, the design of AR-HCF that facilitates optical pulse propagation with desirable properties remains highly intricate and time-consuming. In this work, a modified genetic algorithm (MGA) with a small dataset is presented to reduce the confinement loss (CL) of AR-HCF at the telecom wavelength. The algorithm has been modified through a non-uniform mutation process and a simulated binary crossover method to enhance its searching capability and ensure a stable convergence. The inverse design method for AR-HCF, which combines the algorithm with a full vector finite-element method based on a modal solver, can be implemented to search for approximately optimal designs. In our study, MGA is utilized to optimize the tube diameter and thickness of single-ring tubular AR-HCF and nested anti-resonant nodeless fiber (NANF) at 1550 nm. As a result, optimized ratios of 25.4% and 79.8% are achieved for a core diameter of 40 µm, respectively. In addition, MGA also provides the corresponding optimal range of fiber parameters, which is helpful for actual fabrication.
Brewster mirror ultrafast optical parametric oscillator with high precision wavelength tuning
Authors: Hunter Diana E. , Robarts Sebastian C. , McCracken Richard A. 
Published: October 2023

We demonstrate a synchronously-pumped optical parametric oscillator (OPO) with a cavity formed from high refractive index inverted prisms, also known as Brewster mirrors. Exploiting a single total internal reflection, this is the simplest device capable of deviating a laser beam by 180∘. The OPO produced a chirped signal output tunable from 1060 - 1570 nm with a maximum power of 114 mW. We investigate the geometric properties of ideal and imperfect Brewster mirror prisms and find the latter can provide ∼1000 × finer control of the signal wavelength when compared to cavity length tuning.