bluuebunny/crossref_metadata_2025_split huggingface dataset:
Qualitative evaluation of the health insurance program in Nepal: Expectations beyond limitations
Authors: Acharya Devaraj , Raikhola Pushkar S. , Subedi Kusum R. , Devkota Bhimsen , Bhattarai Radha , Pathak Krishna P. , Kreps Gary L. , Ghimire Rabindra 
Published: June 2023

AbstractThe government of Nepal introduced a national health insurance program in 2016 to comply with the constitution and international commitments to ensure universal health coverage by 2030. This qualitative study explores public perceptions and satisfaction concerning the new health insurance program. The study is guided by an interpretive worldview using both in‐depth interviews (IDIs) and focus group discussions (FGDs). Altogether, 34 (28 IDIs and 6 FGDs) events were conducted covering both self‐ and government‐sponsored health insurance enrollees in the new health insurance program. The study found that insurees had larger expectations as well as both favorable and negative perceptions of the program. Positive perceptions included that the program helped to lower the gap between the wealthy and the poor, increase coverage with fewer financial contributions, and make it easier to receive health services financially. Negative perceptions included long waiting times for registration, consultations, laboratory test results, and pharmacy visits, as well as the lack of drugs, inadequate coverage (a low ceiling), low‐quality services, and strict procedures, which combined to make insurees dissatisfied. We noticed that insurees had expectations that went beyond the program's guidelines, such as the expectation that services would be provided without queues and long waits, that additional services and coverage would be provided, and that preference would be shown for patients who lived far from hospitals. Adequate information, education, and communication‐ and process‐related interventions that address these issues may help minimize the insurees' unrealistic expectations and areas of dissatisfaction.
Theoretical Considerations: Recontextualization and Reformulation in Popularization Discourse
Authors: Sterk Florentine Marnel , van Goch Merel M. 
Published: June 2023

AbstractThis chapter establishes popularization discourse as a genre. In doing so, a distinction can be made between the act of popularization itself and the resulting product of popularization discourse in the form of texts. Popularization draws academic findings into the realm of society and everyday life, which means the focus shifts from the researched phenomenon itself to claims about newsworthiness and the application of findings. The chapter also discusses the two main subgenres of science communication and science journalism, which differ mostly in terms of who produces the discourse, that is, a researcher versus a journalist. The positionality of academic discourse versus popularization discourse is discussed, as the two discourses used to be seen as distinct genres but should be considered as different points on a continuum. The focus is on reformulation and recontextualization as the two main processes in the textual construction of popularization discourse.
Early Dark Energy in Type IIB String Theory
Authors: Cicoli Michele , Licheri Matteo , Mahanta Ratul , McDonough Evan , Pedro Francisco G. , Scalisi Marco 
Published: June 2023

AbstractEarly Dark Energy (EDE) is a promising model to resolve the Hubble Tension, that, informed by Cosmic Microwave Background data, features a generalization of the potential energy usually associated with axion-like particles. We develop realizations of EDE in type IIB string theory with the EDE field identified as either aC4orC2axion and with full closed string moduli stabilization within the framework of either KKLT or the Large Volume Scenario. We explain how to achieve a natural hierarchy between the EDE energy scale and that of the other fields within a controlled effective field theory. We argue that the data-driven EDE energy scale and decay constant can be achieved without any tuning of the microscopic parameters for EDE fields that violate the weak gravity conjecture, while for states that respect the conjecture it is necessary to introduce a fine-tuning. This singles out as the most promising EDE candidates, amongst several working models, theC2axions in LVS with 3 non-perturbative corrections to the superpotential generated by gaugino condensation on D7-branes with non-zero world-volume fluxes.
Clozapine but not lithium reverses aberrant tyrosine uptake in patients with bipolar disorder
Authors: Tabrisi R , Harun-Rashid MD , Montero J , Venizelos N , Msghina M 
Published: June 2023

Abstract
Rationale
Availability of the dopamine and noradrenaline precursor tyrosine is critical for normal functioning, and deficit in tyrosine transport across cell membrane and the blood-brain barrier has been reported in bipolar disorder and schizophrenia. Clozapine and lithium are two psychoactive agents used to treat psychosis, mood disorders and suicidal behavior, but their mechanism of action remains largely unknown.

Objective
To characterize immediate and delayed differences in tyrosine uptake between healthy controls (HC) and bipolar patients (BP) and see if these differences could be normalized by either clozapine, lithium or both. A second objective was to see if clozapine and lithium have additive, antagonistic or synergistic effects in this.

Method
Fibroblasts from five HC and five BP were incubated for 5 min or 6 h with clozapine, lithium, or combination of both. Radioactive labelled tyrosine was used to quantify tyrosine membrane transport.

Results
There was significantly reduced tyrosine uptake at baseline in BP compared to HC, a deficit that grew with increasing incubation time. Clozapine selectively increased tyrosine uptake in BP and abolished the deficit seen under baseline conditions, while lithium had no such effect. Combination treatment with clozapine and lithium was less effective than when clozapine was used alone.

Conclusions
There was significant deficit in tyrosine transport in BP compared to HC that was reversed by clozapine but not lithium. Clozapine was more effective when used alone than when added together with lithium. Potential clinical implications of this will be discussed.
Correlating MRI features with additional genetic markers and patient survival in histological grade 2-3 IDH-mutant astrocytomas
Authors: Lasocki Arian , Buckland Michael E. , Molinaro Tahlia , Xie Jing , Whittle James R. , Wei Heng , Gaillard Frank 
Published: June 2023

Abstract
Purpose
The increasing importance of molecular markers for classification and prognostication of diffuse gliomas has prompted the use of imaging features to predict genotype (“radiogenomics”). CDKN2A/B homozygous deletion has only recently been added to the diagnostic paradigm for IDH[isocitrate dehydrogenase]-mutant astrocytomas; thus, associated radiogenomic literature is sparse. There is also little data on whether different IDH mutations are associated with different imaging appearances. Furthermore, given that molecular status is now generally obtained routinely, the additional prognostic value of radiogenomic features is less clear. This study correlated MRI features with CDKN2A/B status, IDH mutation type and survival in histological grade 2-3 IDH-mutant brain astrocytomas.

Methods
Fifty-eight grade 2–3 IDH-mutant astrocytomas were identified, 50 with CDKN2A/B results. IDH mutations were stratified into IDH1-R132H and non-canonical mutations. Background and survival data were obtained. Two neuroradiologists independently assessed the following MRI features: T2-FLAIR mismatch (<25%, 25–50%, >50%), well-defined tumour margins, contrast-enhancement (absent, wispy, solid) and central necrosis.

Results
8/50 tumours with CDKN2A/B results demonstrated homozygous deletion; slightly shorter survival was not significant (p=0.571). IDH1-R132H mutations were present in 50/58 (86%). No MRI features correlated with CDKN2A/B status or IDH mutation type. T2-FLAIR mismatch did not predict survival (p=0.977), but well-defined margins predicted longer survival (HR 0.36, p=0.008), while solid enhancement predicted shorter survival (HR 3.86, p=0.004). Both correlations remained significant on multivariate analysis.

Conclusion
MRI features did not predict CDKN2A/B homozygous deletion, but provided additional positive and negative prognostic information which correlated more strongly with prognosis than CDKN2A/B status in our cohort.
A prognostic model for predicting progression-free survival in patients with advanced non-small cell lung cancer after image-guided microwave ablation plus chemotherapy
Authors: Kong Fanhao , Yang Honglan , Wang Qiaoxia , Wei Zhigang , Ye Xin 
Published: June 2023

Abstract
Objectives
This study aimed to build and validate a prediction model that can predict progression-free survival (PFS) in patients with advanced non-small cell lung cancer (NSCLC) after image-guided microwave ablation (MWA) plus chemotherapy.

Methods
Data from a previous multi-center randomized controlled trial (RCT) was used and assigned to either the training data set or the external validation data set according to the location of the centers. Potential prognostic factors were identified by multivariable analysis in the training data set and used to construct a nomogram. After bootstraps internal and external validation, the predictive performance was evaluated by concordance index (C-index), Brier Score, and calibration curves. Risk group stratification was conducted using the score calculated by the nomogram. Then a simplified scoring system was built to make risk group stratification more convenient.

Results
In total, 148 patients (training data set: n = 112; external validation data set: n = 36) were enrolled for analysis. Six potential predictors were identified and entered into the nomogram, including weight loss, histology, clinical TNM stage, clinical N category, tumor location, and tumor size. The C-indexes were 0.77 (95% CI, 0.65–0.88, internal validation) and 0.64 (95% CI, 0.43–0.85, external validation). The survival curves of different risk groups also displayed significant distinction (p < 0.0001).

Conclusions
We found weight loss, histology, clinical TNM stage, clinical N category, tumor location, and tumor size were prognostic factors of progression after receiving MWA plus chemotherapy and constructed a prediction model that can predict PFS.

Clinical relevance statement
The nomogram and scoring system will assist physicians to predict the individualized PFS of their patients and decide whether to perform or terminate MWA and chemotherapy according to the expected benefits.

Key Points
• Build and validate a prognostic model using the data from a previous randomized controlled trial to predict progression-free survival after receiving MWA plus chemotherapy.
• Weight loss, histology, clinical TNM stage, clinical N category, tumor location, and tumor size were prognostic factors.
• The nomogram and scoring system published by the prediction model can be used to assist physicians to make clinical decisions.
Formative Evaluierung des personzentrierten Lehrgangs für psychotherapeutischer Medizin in Auseinandersetzung zur personzentrierten Psychotherapieausbildung und Lerntheorie
Authors: Badegruber Michaela , Leibetseder Bettina 
Published: June 2023

ZusammenfassungMit dem personzentrierten Lehrgang (PSY3) für psychotherapeutische Medizin erwerben Ärzt:innen in der psychiatrischen Facharztausbildung der Kepler Universitätsklinik Linz die Berechtigung, eigenständig und selbstverantwortlich psychotherapeutisch-medizinische Behandlungen laut ÖÄK-Diplomrichtlinie durchzuführen. Nun stellt sich die Frage, in wieweit die PSY3 Ausbildung den personzentrierten theoretischen Rahmen vermittelt, welche psychotherapeutischen Handlungskompetenzen erworben werden und ob eine adäquate Persönlichkeitsentwicklung der Ausbildungskandidat:innen stattfindet. Die Ergebnisse einer formativen Evaluierung des Lehrgangs zeigen, dass die Absolvent:innen die determinierten Ausbildungsziele und die nötigen beruflichen Handlungskompetenzen in Bezug zum personzentrierten theoretischen Rahmen erreichen. In Auseinandersetzung mit der personzentrierten Psychotherapieausbildung bestehen aber Unterschiede, da die Lernziele der Psychotherapieausbildung in höheren Taxonomiestufen angesiedelt sind. Eine gesetzliche bzw. curriculare Anpassung der Ärzt:innenausbildung oder ein zusätzliches Up-Grade könnten den Ausgleich der Unterschiede zwischen PSY3 und Psychotherapieausbildung ermöglichen.
An efflux pump in genomic island GI-M202a mediates the transfer of polymyxin B resistance in Pandoraea pnomenusa M202
Authors: Gao Wenhui , Li Congcong , Wang Fengtian , Yang Yilin , Zhang Lu , Wang Zhongxue , Chen Xi , Tan Meixia , Cao Guangxiang , Zong Gongli 
Published: June 2023

Abstract
Background
Polymyxin B is considered a last-line therapeutic option against multidrug-resistant gram-negative bacteria, especially in COVID-19 coinfections or other serious infections. However, the risk of antimicrobial resistance and its spread to the environment should be brought to the forefront.

Methods
Pandoraea pnomenusa M202 was isolated under selection with 8 mg/L polymyxin B from hospital sewage and then was sequenced by the PacBio RS II and Illumina HiSeq 4000 platforms. Mating experiments were performed to evaluate the transfer of the major facilitator superfamily (MFS) transporter in genomic islands (GIs) to Escherichia coli 25DN. The recombinant E. coli strain Mrc-3 harboring MFS transporter encoding gene FKQ53_RS21695 was also constructed. The influence of efflux pump inhibitors (EPIs) on MICs was determined. The mechanism of polymyxin B excretion mediated by FKQ53_RS21695 was investigated by Discovery Studio 2.0 based on homology modeling.

Results
The MIC of polymyxin B for the multidrug-resistant bacterial strain P. pnomenusa M202, isolated from hospital sewage, was 96 mg/L. GI-M202a, harboring an MFS transporter-encoding gene and conjugative transfer protein-encoding genes of the type IV secretion system, was identified in P. pnomenusa M202. The mating experiment between M202 and E. coli 25DN reflected the transferability of polymyxin B resistance via GI-M202a. EPI and heterogeneous expression assays also suggested that the MFS transporter gene FKQ53_RS21695 in GI-M202a was responsible for polymyxin B resistance. Molecular docking revealed that the polymyxin B fatty acyl group inserts into the hydrophobic region of the transmembrane core with Pi-alkyl and unfavorable bump interactions, and then polymyxin B rotates around Tyr43 to externally display the peptide group during the efflux process, accompanied by an inward-to-outward conformational change in the MFS transporter. Additionally, verapamil and CCCP exhibited significant inhibition via competition for binding sites.

Conclusions
These findings demonstrated that GI-M202a along with the MFS transporter FKQ53_RS21695 in P. pnomenusa M202 could mediate the transmission of polymyxin B resistance.
The importance of pregnancy registries for the management of women with epilepsy and childbearing potential: Emphasis on EURAP
Authors: Tomson Torbjörn , Battino Dina 
Published: June 2023

AbstractIn light of the increased awareness of the teratogenic risks with older-generation antiseizure medications (ASMs) and the introduction of many new drugs, prospective antiepileptic drugs and pregnancy registries were introduced some 25 years ago by various independent research groups. The overall aim of these registries is to compare different treatment alternatives with respect to the risk of major congenital malformations (MCM) in the exposed offspring and thus facilitate rational, evidence-based management of women with epilepsy and childbearing potential. The UK and Ireland Epilepsy and Pregnancy Register, the North American AED Pregnancy Registry, EURAP (The International Antiepileptic Drugs and Pregnancy Registry), the Raoul Wallenberg Australian Pregnancy Register, and the Kerala Registry of Epilepsy and Pregnancy are the most important registries established for assessment of specifically the safety of ASMs. Since it is the largest, and being initially European based, EURAP is the focus of this overview of the contribution of pregnancy registries over the years. EURAP and the other registries have provided important information on pregnancy outcomes with the most frequently used ASMs in monotherapy, thereby identifying higher prevalence of MCMs with valproate and topiramate, whereas the risk appears low with lamotrigine and levetiracetam. Further, for several ASMs the risk appears to be dose-dependent. The registries continue to play an important role in efforts to assess the safety of the newer ASMs and of specific combination therapies. Unlike administrative population-based registries, these specific prospective ASM registries also include important information on the mothers’ epilepsy and seizure control.
The influence of autologous cytokine-induced killer cell treatment on the objective efficacy and safety of gefitinib in advanced non-small cell lung cancer
Authors: Qu Shuxian , Liu Zhaozhe , Zheng Zhendong , Ding Zhenyu , Han Tao , Guo Fang , Qiu Jianing , Xie Xiaodong , Ma Dongchu 
Published: June 2023

Abstract

Objective
The aim of the study was to observe the influence of autologous cytokine-induced killer cell (CIK) treatment on the objective efficacy and safety of gefitinib in advanced non-small cell lung cancer (NSCLC).

Methods
Sixty-six patients with NSCLC received gefitinib as second-line treatment. They were randomly divided into 2 groups, and informed consent forms were signed before grouping. Gefitinib was administrated to the control group, and autologous CIK treatment was added to the observation group. The objective treatment and adverse reactions were evaluated in both groups. Results The objective response rate (ORR) and the disease control rate (DCR) of the observation group were slightly higher than those of the control group, although no statistical differences were found between the 2 groups (P > 0.05). The incidences of diarrhea, fatigue, anorexia, oral ulcers, and myelosuppression in the observation group were much lower than those in the control group (P < 0.05). However, there were no statistical differences between the incidences of skin rash, and liver and kidney toxicities (P > 0.05).

Conclusion
Autologous CIK in combination with gefitinib is effective as second-line treatment for advanced NSCLC, and can significantly reduce adverse reactions and improve the objective efficacy.
Novel patterns of cancer genome evolution
Authors: Zhang Xia , Deng Xiaodi , Zhang Yu , Li Zhiguang 
Published: June 2023

Abstract
Cells usually undergo a long journey of evolution during the progression from normal to precancerous cells and finally to full-fledged cancer cells. Multiple genomic aberrations are acquired during this journey that could either act as drivers to confer significant growth advantages or act as passengers with little effect on the tumor growth. Recent advances in sequencing technology have made it feasible to decipher the evolutionary course of a cancer cell on a genome-wide level by evaluating the relative number of mutated alleles. Novel terms such as chromothripsis and chromoplexy have been introduced to describe the newly identified patterns of cancer genome evolution. These new insights have greatly expanded our understanding of the initiation and progression of cancers, which should aid in improving the efficiency of cancer management and treatment.
Intravoxel incoherent motion magnetic resonance imaging for diagnosis of cervical cancer and evaluation of response of uterine cervical cancer to radiochemotherapy: A pilot study ⁎
Authors: Wang Yanchun , Hu Shan , Hu Xuemei , Li Jianjun , Shen Yaqi , Liu Xiaoyu , Wang Zhi , Meng Xiaoyan , Li Zhen , Hu Daoyu 
Published: June 2023

Abstract

Objective
The aim of this study was to investigate the ability of intravoxel incoherent motion (IVIM) diffusion-weighted magnetic resonance imaging (MRI) to diagnose cervical cancer and to evaluate the response of uterine cervical cancer to radiochemotherapy (CRT).

Methods
This prospective study was approved by the institutional review board, and informed consent was obtained from all patients. A total of 23 patients with primary cervical cancer who were undergoing CRT and 16 age-matched healthy subjects were prospectively recruited for IVIM (b = 0-800 s/mm2) and standard pelvic MRI. Bi-exponential analysis was performed to derive f (perfusion fraction), D⁎ (pseudo-diffusion coefficient), and D (true molecular diffusion coefficient) in cervical cancer (n = 23) and the normal cervix (n = 16). The apparent diffusion coefficient (standard ADC) was calculated. The independent-samples t-test and paired-samples t-test were used for comparisons.

Results
Pre-treatment cervical cancer had the lowest standard ADC (1.15 ± 0.13 × 10-3 mm2/s) and D (0.89 ± 0.10 × 10-3 mm2/s) values, and these were significantly different from the normal cervix and posttreatment cervical cancer (P = 0.00). The f (16.67 ± 5.85%) was lowest in pre-treatment cervical cancer and was significantly different from the normal cervix and post-treatment cervical cancer (p = 0.012 and 0.00, respectively). No difference was observed in D⁎.

Conclusion
IVIM is potentially promising for differentiating between the normal cervix and cervical cancer because pre-treated cervical cancer has low perfusion and diffusion IVIM characteristics. Further, the standard ADC, D, and f of cervical cancer showed a tendency to normalize after CRT; thus, IVIM may be useful for monitoring the response to CRT in cervical cancer.
A clinical study on salvage hepatectomy for treating recurrent liver cancer after radiofrequency ablation
Authors: Xiong Qing , Feng Xiaobin , Yan Jun , Xia Feng , Li Xiaowu , Ma Kuansheng , Bie Ping 
Published: June 2023

AbstractObjectiveWe studied the efficacy of salvage hepatectomy for treating recurrent hepatic cancer after radiofrequency ablation (RFA).MethodsA retrospective analysis of 67 patients who had recurrent liver cancer after RFA treatment and received salvage hepatectomy in the Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (China), from January 2006 to January 2014, was performed. The analysis included patient gender, age, hepatitis type, alpha-fetoprotein (AFP), and TNM stage prior to RFA and salvage hepatectomy, overall survival rates, and tumor-free survival rates after salvage hepatectomy.ResultsAmong the 67 patients, there were 57 cases of hepatitis B, two cases of hepatitis C, and eight cases did not have hepatitis. AFP levels in patients ranged from 3 to 4521 ng/mL (median 33 ng/mL). Before RFA, 54 cases were stage I tumors, and 13 were stage II tumors. Tumor sizes varied from 0.82 to 4.83 cm (median 3.0 cm). In 20 cases, one RFA was performed, and for 47 cases, RFA was repeated. RFAablated region diameters ranged from 3.8 to 5.2 cm (median 4.5 cm). The interval between the salvage surgical resection and RFA was 3-37 months. Before salvage hepatectomy, 23 stage I tumors, 12 stage II tumors, and 32 stage III tumors were present (size ranged 4.83-11.84 cm; median 6.3 cm). For salvage hepatectomy, laparotomy was performed for 56 cases, and laparoscopy was performed for 28 cases. Inflow clamping was performed for 39 cases (15-45 min). Surgery was 219-370 min and intraoperative blood loss was 100-2100 mL. For 13 cases, intraoperative blood transfusion was required. Tumor pathological data revealed 31, 35, and 1 poorly, moderately, and well differentiated tumors, respectively. No patients died due to operative complications, and hospital stays were 8-10 days. Overall and tumor-free survival rates were 85% and 79% for 1 year, 50% and 20% for 3 years, and 39% and 19% for 5 years, respectively. Kaplan-Meier analysis and Cox regression confirmed that tumor number and size prior to salvage liver cancer were risk factors affecting survival.ConclusionPatients who received RFA to treat early-stage liver cancer with postoperative recurrent stage I tumors have satisfactory outcomes with salvage hepatectomy.