bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic value of IDH2R140 and IDH2R172 mutations in patients with acute myeloid leukemia: a systematic review and meta-analysis
Authors: Qin Yao , Shen Kai , Liu Ting , Ma Hongbing
Published: June 2023

Background

Whether isocitrate dehydrogenase 2 (IDH2) R140 and R172 gene mutations affect the prognosis of patients with acute myeloid leukemia (AML) is controversial. Here, we performed a meta-analysis to assess their prognostic value.

Methods

Eligible studies were systematically searched from PubMed, Embase, the Cochrane Library and Chinese databases up to June 1, 2022. We extracted the hazard ratios (HRs) and their 95% confidence intervals (CIs) of overall survival (OS) and progression-free survival (PFS) to carry out a meta-analysis by a fixed effect model or random effect model according to the heterogeneity between studies.

Results

A total of 12725 AML patients from 11 studies were included in this meta-analysis, of which 1111 (8.7%) and 305 (2.4%) had IDH2R140 and IDH2R172 mutations, respectively. The results revealed that both IDH2R140 and IDH2R172 mutations had no significant effect on OS (IDH2R140: HR = 0.92, 95% CI: 0.77–1.10, P = 0.365; IDH2R172: HR = 0.91, 95% CI: 0.65–1.28, P = 0.590) or PFS (IDH2R140: HR = 1.02, 95% CI: 0.75–1.40, P = 0.881; IDH2R172: HR = 1.31, 95% CI: 0.78–2.22, P = 0.306) in AML patients. Subgroup analysis of AML patients with IDH2R140 mutation revealed that studies from the USA (HR = 0.60, 95% CI: 0.41–0.89, P = 0.010) and ≤ 50 years old (HR = 0.63, 95% CI: 0.50–0.80, P = 0.000) had longer OS. However, studies from Sweden (HR = 1.94, 95% CI: 1.07–3.53, P = 0.030) had shorter OS. Meanwhile, subgroup analysis of AML patients with IDH2R172 mutation showed that studies from Germany/Austria (HR = 0.76, 95% CI: 0.61–0.94, P = 0.012) and from Sweden (HR = 0.22, 95% CI: 0.07–0.74, P = 0.014) had longer OS, whereas studies from the UK (HR = 1.49, 95% CI: 1.13–1.96, P = 0.005) and studies with nonmultivariate analysis of data type (HR = 1.35, 95% CI: 1.06–1.73, P = 0.014) had shorter OS. In addition, our study also found that patients with IDH2R140 mutation had significantly longer OS (HR = 0.61, 95% CI: 0.39–0.96, P = 0.032) and PFS (HR = 0.31, 95% CI: 0.18–0.52, P = 0.021) than patients with IDH2R172 mutation, despite some degree of heterogeneity.

Conclusions

This meta-analysis demonstrates that IDH2R140 mutation improves OS in younger AML patients and that the prognostic value of IDH2R172 mutation is significantly heterogeneous. Differences in region and data type have a significant impact on the prognosis of AML patients with IDH2R140 and/or IDH2R172 mutations. Additionally, AML patients with IDH2R140 mutation have a better prognosis than those with IDH2R172 mutations, albeit with some degree of heterogeneity.
Decomposing socioeconomic inequalities in dental caries among Chinese adults: findings from the 4th national oral health survey
Authors: Chang Qing , Cheng Menglin , Xu Mengru , Du Shuo , Wang Xing , Feng Xiping , Tai Baojun , Hu Deyu , Lin Huancai , Wang Bo , Wang Chunxiao , Zheng Shuguo , Liu Xuenan , Rong Wensheng , Wang Weijian , Dong Yanmei , Si Yan
Published: June 2023

Objective

This cross-sectional study aimed to investigate socioeconomic inequalities in dental caries among adults (35 years and older) in China and explore the contributions of various factors to these inequalities.

Methods

This study included 10,983 adults (3,674 aged 35–44 years, 3,769 aged 55–64 years and 3,540 aged 65–74 years) who participated in the 4th National Oral Health Survey (2015–2016) in China. Dental caries status was evaluated by the decayed, missing and filled teeth (DMFT) index. Concentration indices (CIs) were applied to quantify the different degrees of socioeconomic-related inequality in DMFT, decayed teeth with crown or root caries (DT), missing teeth due to caries or other reasons (MT), and filled teeth without any primary or secondary caries (FT) among adults of different age groups. Decomposition analyses were conducted to identify the determinants and their associations with inequalities in DMFT.

Results

The significant negative CI indicated that DMFT for the total sample were concentrated among socioeconomically disadvantaged adults (CI = − 0.06; 95% confidence interval [CI], − 0.073 to − 0.047). The CIs for DMFT for adults aged 55–64 and 65–74 years were − 0.038 (95% CI, − 0.057 to − 0.018) and − 0.039 (95% CI, − 0.056 to − 0.023), respectively, while the CI for DMFT for adults aged 35–44 years was not statistically significant (CI = − 0.002; 95% CI, − 0.022 to 0.018). The concentration indices of DT were negative and concentrated in disadvantaged populations, while FT showed pro-rich inequalities in all age groups. Decomposition analyses showed that age, education level, toothbrushing frequency, income and type of insurance contributed substantially to socioeconomic inequalities, accounting for 47.9%, 29.9%, 24.5%,19.1%, and 15.3%, respectively.

Conclusion

Dental caries was disproportionately concentrated among socioeconomically disadvantaged adults in China. The results of these decomposition analyses are informative for policy-makers attempting to develop targeted health policy recommendations to reduce dental caries inequalities in China.
The clinical and pathological characteristics of lipid-rich carcinoma of the breast: an analysis of 98 published patients
Authors: Zhang Mengdi , Pu Dongqing , Shi Guangxi , Li Jingwei
Published: June 2023

Background

Due to the small number of cases and few literature reports, the clinical treatment and prognosis of lipid-rich carcinoma of the breast are not summarized, which will lead to misdiagnosis and mistreatment and delay the patient’s condition. This study collected published case reports and analyzed the clinical characteristics of lipid-rich carcinoma of the breast in order to provide reference for early diagnosis and treatment of the disease.

Methods

We performed a search using the PubMed, ClinicalTrials.gov, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases for publicly published case reports of lipid-rich carcinoma of the breast and obtained basic information of the patients such as country, age, sex, onset site, surgical method, pathology, postoperative treatment, follow-up time, and outcome (Table 9). The data were analyzed using Statistical Product Service Solutions (SPSS).

Results

The mean age of the patients at diagnosis was 52.79 years and the median age was 53 years. Breast masses were the main clinical manifestations, with the upper outer quadrant (53.42%) being the most common. The treatment for lipid-rich carcinoma of the breast is mainly surgery plus postoperative adjuvant radiotherapy and chemotherapy. According to the results of this study, the surgical method recommended modified radical mastectomy (46.59%). Lymph node metastasis was found in 50.60% of the patients at the time of the first diagnosis. Patients who received postoperative adjuvant chemotherapy and radiotherapy had the highest disease-free survival and overall survival.

Conclusion

Lipid-rich carcinoma of the breast has a short course of disease and early lymphatic or blood metastasis, and its prognosis is poor. In this study, we summarize the clinical and pathological characteristics to provide ideas for the early diagnosis and treatment of lipid-rich carcinoma of the breast.
Willingness to practice medicine and related influential factors among medical undergraduates during COVID-19: a cross-sectional study
Authors: Yu Shuang , Zou Fengjuan , Wang Qian , Zhou Kai , Jian Ronghua , Jin Yingying , Hu Yijun , Zhu Sui
Published: June 2023

Background

As the medical undergraduates constitute the future workforce in China, their career preferences hold a significant bearing on the quality of healthcare services, particularly in light of the ongoing COVID-19 pandemic. We aim to understand the current state of the willingness to practice medicine among medical undergraduates and to analyze the related influential factors.

Methods

During the COVID-19 epidemic, we conducted a cross-sectional survey via an online platform from February 15, 2022, to May 31, 2022, to collect participants’ demographic information, psychology, and factors influencing their career choices. The general self-efficacy scale (GSES) was used to evaluate medical students’ perceptions of their self-efficacy. Futhermore, we conducted multivariate logistic regression analyses to explore the influencing factors of medical undergraduates’ willingness to pursure a caree in medicine.

Results

A total of 2348 valid questionnaires were included, and 1573 (66.99%) were willing to practice medicine for medical undergraduates after graduation. The mean GESE scores in the willingness group (2.87 ± 0.54) were significantly higher than those of the unwillingness group (2.73 ± 0.49). The multiple logistic regression showed that several factors were positively associated with willingness to practice medicine as a career, including students’ GSES score (OR = 1.87), current major, household income, personal ideals (OR = 1.97), family support (OR = 1.44), high income (OR = 1.77), and social respect (OR = 2.19). Compared with those who were very afraid of COVID-19, students who did not express any fear towards the COVID-19 pandemic had a higher preference for choosing the medical profession as a career. Conversely, students thinking of high tension in the doctor-patient relationship, heavy workload, and long training were less likely to choose medical work after graduation.

Conclusions

The study highlights a noteworthy prevalence of medical undergraduates who expressed their willingness to pursue medicine as a career post-graduation. Several factors, including but not limited to current major, household income, psychological factors, personal preferences, and career needs or preferences, were significantly associated with this willingness. Moreover, the impact of the COVID-19 pandemic on medical students’ career choices cannot be overlooked.
Cost-effectiveness of hypofractionated versus conventional fractionated radiotherapy for the treatment of men with early glottic cancer: a study in the Brazilian public and private health system
Authors: Lourenção Marina , Arruda Gustavo Viani , Rocha Lucas Penna , Galendi Julia Simões Corrêa , de Oliveira Jorge Caldeira , Jacinto Alexandre Arthur
Published: June 2023

Background

This study aims to evaluate whether hypofractionated radiotherapy (HYPOFRT) is a cost-effective strategy than conventional fractionated radiotherapy (CFRT) for early-stage glottic cancer (ESGC) in the Brazilian public and private health systems.

Methods

Adopting the perspective of the Brazilian public and private health system as the payer, a Markov model with a lifetime horizon was built to delineate the health states for a cohort of 65-year-old men after with ESGC treated with either HYPOFRT or CFRT. Probabilities of controlled disease, local failure, distant metastasis, and death and utilities scores were extracted from randomized clinical trials. Costs were based on the public and private health system reimbursement values.

Results

In the base case scenario, for both the public and private health systems, HYPOFRT dominated CFRT, being more effective and less costly, with a negative ICER of R$264.32 per quality-adjusted life-year (QALY) (public health system) and a negative ICER of R$2870.69/ QALY (private health system). The ICER was most sensitive to the probability of local failure, controlled disease, and salvage treatment costs. For the probabilistic sensitivity analysis, the cost-effectiveness acceptability curve indicates that there is a probability of 99.99% of HYPOFRT being cost-effective considering a willingness-to-pay threshold of R$2,000 ($905.39) per QALY (public sector) and willingness-to-pay threshold of R$16,000 ($7243.10) per QALY (private sector). The results were robust in deterministic and probabilistic sensitivity analyses.

Conclusions

Considering a threshold of R$ 40,000 per QALY, HYPOFRT was cost-effective compared to CFRT for ESGC in the Brazilian public health system. The Net Monetary Benefit (NMB) is approximately 2,4 times (public health system) and 5,2 (private health system) higher for HYPOFRT than CFRT, which could open the opportunity of incorporating new technologies.
Disparities in modern health service utilization across socio-demographic and economic inequalities among households in Gida Ayana district, Oromia Regional state, Ethiopia: a community-based cross-sectional study
Authors: Geta Edosa Tesfaye , Wakjira Abebe , Hailu Wase Benti
Published: June 2023

Background

Health care disparities (HCD) occur across a broad range of dimensions and achieving equity in health care is a strenuous task. To overcome the disparities, countries worldwide have started implementing varies policies. HCD remains a challenge in the health care system of Ethiopia. Hence, the study aimed to estimate the disparities in health care utilization (HCU) among households.

Methods

A community-based cross-sectional study was conducted from February 01 to April 30, 2022, among households in Gida Ayana District, Ethiopia. A single population proportion formula was used to determine the 393sample size, and participants were selected using systematic sampling. Data was entered into Epi-data 4.6 and exported to SPSS 25 for analysis. Descriptive analysis and binary and multivariable logistic regressions were performed.

Results

Of the 356 households that participated in the study, 321 (90.2%) of them reported at least one member of their family perceived morbidity in the last six months. The overall level of HCU determined was 207(64.5%), 95% confidence interval (CI),59.0-69.7%. Urban residents (AOR = 3.68, 95% CI = 1.94–6.97), attending secondary school and above (AOR = 2.79, CI = 1.27–5.98), rich (AOR = 2.47, CI = 1.03–5.92), small families (AOR = 2.83, CI = 1.26–6.55), and insured (AOR = 4.27, CI = 2.36–7.71) significantly contributed to HCD.

Conclusions

Households’ overall level of HCU for perceived morbidity was moderate. However, significant disparities were observed in HCU across place of residence, wealth status, level of education, family size, and health insurance. Hence, strengthening the strategy of financial protection by implementing health insurance that focuses on the socio-demographic and economic status of households is recommended to reduce the disparities.
‘Survivorship care is one big gap’: a qualitative study of post-treatment supportive care in Aotearoa New Zealand
Authors: Bateman Jerram , Egan Richard , Maclennan Karyn
Published: June 2023

Background

This study focuses on the provision of supportive care services and programmes for cancer survivors post-treatment in Aotearoa New Zealand (NZ). It aims to aid our understanding of an often challenging and fragmented phase of cancer survivorship, and lay the groundwork for future research into the development of survivorship care in NZ.

Methods

This study employed a qualitative design using semi-structured interviews with a range of healthcare providers (n = 47) involved in service provision for cancer survivors post active treatment, including supportive care providers; clinical and allied health providers; primary health providers; and Māori health providers. Data were analysed using thematic analysis.

Results

We found that cancer survivors in NZ face a range of psycho-social and physical issues post-treatment. The provision of supportive care to meet these needs is currently fragmented and inequitable. The key barriers to improved supportive care provision for cancer survivors post-treatment include a lack of capacity and resources within the existing cancer care framework; divergent attitudes to survivorship care within the cancer care workforce; and a lack of clarity around whose responsibility post-treatment survivorship care is.

Conclusions

Post-treatment cancer survivorship should be established as a distinct phase of cancer care. Measures could include greater leadership in the survivorship space; the implementation of a survivorship model(s) of care; and the use of survivorship care plans; all of which could help improve referral pathways, and clarify clinical responsibility for post-treatment survivorship care.
The association between air pollution and the severity at diagnosis and progression of systemic sclerosis-associated interstitial lung disease: results from the retrospective ScleroPol study
Authors: Roeser Anaïs , Sese Lucile , Chassagnon Guillaume , Chaigne Benjamin , Dunogue Bertrand , Tran Ba Stéphane , Jebri Salma , Brillet Pierre-Yves , Revel Marie Pierre , Aubourg Frédérique , Dhote Robin , Caux Frédéric , Annesi-Maesano Isabella , Mouthon Luc , Nunes Hilario , Uzunhan Yurdagül
Published: June 2023

Objective

To investigate the association of air pollution exposure with the severity of interstitial lung disease (ILD) at diagnosis and ILD progression among patients with systemic sclerosis (SSc)-associated ILD.

Methods

We conducted a retrospective two-center study of patients with SSc-associated ILD diagnosed between 2006 and 2019. Exposure to the air pollutants particulate matter of up to 10 and 2.5 µm in diameter (PM10, PM2.5), nitrogen dioxide (NO2), and ozone (O3) was assessed at the geolocalization coordinates of the patients’ residential address. Logistic regression models were used to evaluate the association between air pollution and severity at diagnosis according to the Goh staging algorithm, and progression at 12 and 24 months.

Results

We included 181 patients, 80% of whom were women; 44% had diffuse cutaneous scleroderma, and 56% had anti-topoisomerase I antibodies. ILD was extensive, according to the Goh staging algorithm, in 29% of patients. O3 exposure was associated with the presence of extensive ILD at diagnosis (adjusted OR: 1.12, 95% CI 1.05–1.21; p value = 0.002). At 12 and 24 months, progression was noted in 27/105 (26%) and 48/113 (43%) patients, respectively. O3 exposure was associated with progression at 24 months (adjusted OR: 1.10, 95% CI 1.02–1.19; p value = 0.02). We found no association between exposure to other air pollutants and severity at diagnosis and progression.

Conclusion

Our findings suggest that high levels of O3 exposure are associated with more severe SSc-associated ILD at diagnosis, and progression at 24 months.
Robotic-assisted tumor enucleation versus robotic-assisted partial nephrectomy for intermediate and high complexity renal cell carcinoma: a single-institution experience
Authors: Lei Kunyang , Wang Xu , Yang Zhongsheng , Zhong Yuming , Liu Yifu , Sun Ting
Published: June 2023

Objectives

To compare the perioperative and oncological outcomes of robotic-assisted tumor enucleation (RATE) and robotic-assisted partial nephrectomy (RAPN) in the treatment of intermediate and high complexity renal cell carcinoma (RCC).

Methods

We retrospectively collected the data of 359 patients with intermediate and high complexity RCC who underwent RATE and RAPN. The perioperative, oncological, and pathological outcomes of the two groups were compared, and univariate and multivariate analyses were used to evaluate the risk factors for warm ischemia time (WIT) > 25 min.

Results

Compared with RAPN group, patients in RATE group had shorter operative time (P < 0.001), shorter WIT (P < 0.001), and less estimated blood loss (EBL) (P < 0.001). The decrease rate of estimated glomerular filtration rate (eGFR) in RATE group was better than that in RAPN group (P < 0.001). Multivariable analysis showed that RAPN and higher PADUA score were independent risk factors for WIT > 25 min (both P < 0.001). The rate of positive surgical margin was similar between the two groups, but the local recurrence rate of the RATE group was higher than that of the RAPN group (P = 0.027).

Conclusions

RATE and RAPN have similar oncological outcomes for the treatment of intermediate and high complexity RCC. In addition, RATE was superior to RAPN in perioperative outcomes.
Assessing the comparability of cycle threshold values derived from five external quality assessment rounds for omicron nucleic acid testing
Authors: Fan Gaowei , Jin Yali , Wang Qingtao , Yue Yuhong
Published: June 2023

Background

A variety of open-system real-time reverse transcriptase polymerase chain reaction (RT-PCR) assays for several acute respiratory syndrome coronavirus 2 are currently in use. This study aimed to ensure the quality of omicron nucleic acid testing and to assess the comparability of cycle threshold (Ct) values derived from RT-PCR.

Methods

Five external quality assessment (EQA) rounds using the omicron virus-like particles were organized between February 2022 and June 2022.

Results

A total of 1401 qualitative EQA reports have been collected. The overall positive percentage agreement was 99.72%, the negative percentage agreement was 99.75%, and the percent agreement was 99.73%. This study observed a significant variance in Ct values derived from different test systems. There was a wide heterogeneity in PCR efficiency among different RT-PCR kits and inter-laboratories.

Conclusion

There was strong concordance among laboratories performing qualitative omicron nucleic acid testing. Ct values from qualitative RT-PCR tests should not be used for clinical or epidemiological decision-making to avoid the potential for misinterpretation of the results.
Range of motion of the mid-cervical spine: human versus goat
Authors: Dong Jun , Zhang Gelin , Sun Yuan , Li Xi , Zhang Xuyan , Liu Min , Liu Ruoxi , Fan Liying
Published: June 2023

Background

The goat cervical spine represents a promising alternative for human specimen in spinal implant testing, but the range of motion (ROM) of the spine is lacking. We aimed to evaluate and compare the ROMs of fresh goat and human mid-cervical spine specimens.

Methods

Ten fresh adult healthy male goat cervical spine specimens (G group) and ten fresh frozen adult healthy human cervical spine specimens (average age: 49.5 ± 12.1 years; 6 males, 4 females) (H group) were included. The ROMs of each specimen were biomechanically tested at the C2–3, C3–4, C4–5 and C2–5 levels at 1.5 Nm and 2.5 Nm torque and recorded. The ROMs of different levels of goat cervical samples were compared to those of human cervical samples using an independent sample t test. Significance was defined as a P value of less than 0.05.

Results

At the C2–3, C3–4 and C4–5 levels, the ROMs of the goat cervical spine were significantly larger than those of the human cervical spine in all directions except extension under 1.5 Nm torque; under 2.5 Nm torque, the ROMs of the goat cervical spine at the C2–3 and C3–4 levels were significantly larger than those of humans in the pure movement of flexion, lateral bending and axial rotation, and the ROMs for axial rotation of the goat specimens and human specimens were comparable. Under both 1.5 Nm and 2.5 Nm torque, the goat cervical spine displayed a much greater ROM in all directions at the C2–5 level.

Conclusions

Several segmental ROMs of fresh goat and human cervical spine specimens were recorded in this investigation. We recommend using goat cervical specimens as an alternative to fresh human cervical specimens in future studies when focusing only on the ROMs of C2–3, C3–4 and C4–5 in flexion under a torque of 1.5 Nm or the ROMs of C2–3 and C3–4 in flexion and rotation under a torque of 2.5 Nm.
Maternal body mass index and risk of fetal overgrowth in women with gestational diabetes Mellitus in Southeast China: a retrospective cohort study
Authors: Lin Lihua , Wu Jianhang , Xu Libo , Fang Jianqi , Lin Juan
Published: June 2023

Background

To investigate the relationship between body mass index (BMI) changes and large for gestational age (LGA) in women with gestational diabetes mellitus (GDM).

Methods

A retrospective cohort study including 10,486 women with GDM was conducted. A dose‒response analysis of BMI changes and the occurrence of LGA was performed. Binary logistic regressions were performed to assess crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Receiver operating characteristic (ROC) curves and areas under the curve (AUCs) were used to assess the ability of BMI changes to predict LGA.

Results

The probability of LGA increased with increasing BMI. The risk of LGA increased across the BMI change quartiles. The BMI change remained positively associated with the risk of LGAafter stratification analysis. The AUC was 0.570 (95% CI: 0.557 ~ 0.584)in the entire study population, and the best optimal predictive cut-off value was 4.922, with a sensitivity of 0.622 and a specificity of 0.486. The best optimal predictive cut-off value decreased from the underweight group to the overweight and obese group.

Conclusions

BMI changes are related to the risk of LGA and may be a useful predictor of the incidence of LGA in singleton pregnant women with GDM.
Comparative evaluation of clinical and cerebrospinal fluid biomarker characteristics in rapidly and non-rapidly progressive Alzheimer’s disease
Authors: Herden Janne Marieke , Hermann Peter , Schmidt Isabel , Dittmar Kathrin , Canaslan Sezgi , Weglage Luise , Nuhn Sabine , Volpers Corinna , Schlung Astrid , Goebel Stefan , Kück Fabian , Villar-Piqué Anna , Schmidt Christian , Wedekind Dirk , Zerr Inga
Published: June 2023

Background

Rapidly progressive forms of Alzheimer’s disease (rpAD) are increasingly recognized and may have a prevalence of up to 30% of patients among all patients with Alzheimer’s disease (AD). However, insights about risk factors, underlying pathophysiological processes, and clinical characteristics of rpAD remain controversial. This study aimed to gain a comprehensive picture of rpAD and new insights into the clinical manifestation to enable a better interpretation of disease courses in clinical practice as well as in future clinical studies.

Methods

Patients (n = 228) from a prospective observational study on AD were selected and categorized into rpAD (n = 67) and non-rpAD (n = 161) disease groups. Patients were recruited through the German Creutzfeldt-Jakob disease surveillance center and the memory outpatient clinic of the Göttingen University Medical Center, representing diverse phenotypes of the AD population. Biomarkers and clinical presentation were assessed using standardized protocols. A drop of ≥ MMSE 6 points within 12 months defined rapid progressors.

Results

Lower CSF Amyloid beta 1–42 concentrations (p = 0.048), lower Amyloid beta 42/40 ratio (p = 0.038), and higher Tau/Amyloid-beta 1–42 ratio, as well as pTau/Amyloid-beta 1–42 ratio (eachp = 0.004) were associated with rpAD. Analyzes in a subset of the cohort (rpAD:n = 12; non-rpAD:n = 31) showed higher CSF NfL levels in rpAD (p = 0.024). Clinically, rpAD showed earlier impairment of functional abilities (p < 0.001) and higher scores on the Unified Parkinson’s Disease Rating Scale III (p < 0.001), indicating pronounced extrapyramidal motor symptoms. Furthermore, cognitive profiles (adjusted for overall cognitive performance) indicated marked deficits in semantic (p = 0.008) and phonematic (0.023) verbal fluency tests as well as word list learning (p = 0.007) in rpAD compared to non-rpAD. The distribution of APOE genotypes did not differ significantly between groups.

Conclusions

Our results suggest that rpAD is associated with distinct cognitive profiles, earlier occurrence of non-cognitive symptoms, extrapyramidal motoric disturbance, and lower Amyloid-beta 1–42 concentrations in the CSF. The findings may help to characterize a distinct phenotype of rpAD and estimate prognosis based on clinical characteristics and biomarker results. However, an important future goal should be a unified definition for rpAD to enable targeted study designs and better comparability of the results.
Blood and CSF chemokines in Alzheimer’s disease and mild cognitive impairment: a systematic review and meta-analysis
Authors: Zhou Futao , Sun Yangyan , Xie Xinhua , Zhao Yushi
Published: June 2023

Objective

Chemokines, which are chemotactic inflammatory mediators involved in controlling the migration and residence of all immune cells, are closely associated with brain inflammation, recognized as one of the potential processes/mechanisms associated with cognitive impairment. We aim to determine the chemokines which are significantly altered in Alzheimer’s disease (AD) and mild cognitive impairment (MCI), as well as the respective effect sizes, by performing a meta-analysis of chemokines in cerebrospinal fluid (CSF) and blood (plasma or serum).

Methods

We searched three databases (Pubmed, EMBASE and Cochrane library) for studies regarding chemokines. The three pairwise comparisons were as follows: AD vs HC, MCI vs healthy controls (HC), and AD vs MCI. The fold-change was calculated using the ratio of mean (RoM) chemokine concentration for every study. Subgroup analyses were performed for exploring the source of heterogeneity.

Results

Of 2338 records identified from the databases, 61 articles comprising a total of 3937 patients with AD, 1459 with MCI, and 4434 healthy controls were included. The following chemokines were strongly associated with AD compared with HC: blood CXCL10 (RoM, 1.92, p = 0.039), blood CXCL9 (RoM, 1.78, p < 0.001), blood CCL27 (RoM, 1.34, p < 0.001), blood CCL15 (RoM, 1.29, p = 0.003), as well as CSF CCL2 (RoM, 1.19, p < 0.001). In the comparison of AD with MCI, there was significance for blood CXCL9 (RoM, 2.29, p < 0.001), blood CX3CL1 (RoM, 0.77, p = 0.017), and blood CCL1 (RoM, 1.37, p < 0.001). Of the chemokines tested, blood CX3CL1 (RoM, 2.02, p < 0.001) and CSF CCL2 (RoM, 1.16, p = 0.004) were significant for the comparison of MCI with healthy controls.

Conclusions

Chemokines CCL1, CCL2, CCL15, CCL27, CXCL9, CXCL10, and CX3CL1 might be most promising to serve as key molecular markers of cognitive impairment, although more cohort studies with larger populations are needed.
Adaptive language model training for molecular design
Authors: Blanchard Andrew E. , Bhowmik Debsindhu , Fox Zachary , Gounley John , Glaser Jens , Akpa Belinda S. , Irle Stephan
Published: June 2023

The vast size of chemical space necessitates computational approaches to automate and accelerate the design of molecular sequences to guide experimental efforts for drug discovery. Genetic algorithms provide a useful framework to incrementally generate molecules by applying mutations to known chemical structures. Recently, masked language models have been applied to automate the mutation process by leveraging large compound libraries to learn commonly occurring chemical sequences (i.e., using tokenization) and predict rearrangements (i.e., using mask prediction). Here, we consider how language models can be adapted to improve molecule generation for different optimization tasks. We use two different generation strategies for comparison, fixed and adaptive. The fixed strategy uses a pre-trained model to generate mutations; the adaptive strategy trains the language model on each new generation of molecules selected for target properties during optimization. Our results show that the adaptive strategy allows the language model to more closely fit the distribution of molecules in the population. Therefore, for enhanced fitness optimization, we suggest the use of the fixed strategy during an initial phase followed by the use of the adaptive strategy. We demonstrate the impact of adaptive training by searching for molecules that optimize both heuristic metrics, drug-likeness and synthesizability, as well as predicted protein binding affinity from a surrogate model. Our results show that the adaptive strategy provides a significant improvement in fitness optimization compared to the fixed pre-trained model, empowering the application of language models to molecular design tasks.
Analysis of a free boundary problem modeling spherically symmetric tumor growth with angiogenesis and a periodic supply of nutrients
Authors: Xu Shihe , Bai Meng
Published: June 2023

In this paper, we study a free boundary problem modeling spherically symmetric tumor growth with angiogenesis and a periodic supply of nutrients. The mathematical model is a free boundary problem since the external radius of the tumor denoted by $R(t)$
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Combined Use of Sewage Sludge Ash and Silica Fume in Concrete
Authors: Azarhomayun Fazel , Haji Mohammad , Kioumarsi Mahdi , Kheyroddin Ali
Published: June 2023

The lack of adequate space for sewage sludge disposal has become a significant challenge in many countries. Landfilling and using sewage sludge as fertilizer in agricultural lands are the main methods for disposal. However, these methods can result in soil and groundwater contamination as well as heavy metal and microbial pollution in soil. An alternative disposal method is using sewage sludge ash (SSA) in concrete production. If the sludge ash is reactive, it can replace a portion of cement in concrete; otherwise, it can be used as a filler. In the present study, X-ray fluorescence (XRF) experiments were conducted to determine the elemental composition of sewage sludge. Then, the sewage sludge was incinerated, and XRF and X-ray diffraction (XRD) tests were performed on the resulting sewage sludge ash. The ash was utilized in different proportions in the mortar and concrete specimens, and compressive strength tests were conducted on the resulting specimens. The results indicate that using 20% SSA instead of cement resulted in a 25% reduction in compressive strength in concrete specimens. However, the combination of 10% silica fume and 10% SSA was the optimal combination to compensate for the reduction in compressive strength caused using SSA.
Challenges and advances in materials and fabrication technologies of small-diameter vascular grafts
Authors: Li Mei-Xian , Wei Qian-Qi , Mo Hui-Lin , Ren Yu , Zhang Wei , Lu Huan-Jun , Joung Yoon Ki
Published: June 2023

Highlights

• The commonly used synthetic polymers for vascular grafts are reviewed.

• Various methods for surface modification of artificial vascular grafts are summarized.

• Latest fabrication techniques for small-diameter vascular grafts and their mechanical and biological properties are systematically summarized.

• Current state and future perspective of small-diameter vascular grafts are suggested.
“Take a walk in someone else’s shoes”: the role of participatory arts for health research development and training
Authors: Gillibrand Stephanie , Hine Paul , Conyers Rob , Gravestock Jason , Walsh Cole , McAvoy Aneela , Sanders Caroline
Published: June 2023

Participatory arts are increasingly recognised as a valuable and accessible mechanism for giving a voice to the experiences of individuals’ health and healthcare. In recent years, there has been a move towards embedding participatory arts-based models into public engagement processes. Here, we contribute to the existing literature on the use of participatory arts-based approaches and their role in health research and healthcare practise, focusing on two interlinked approaches, the creation of personas and storytelling. We draw on two recent projects which have utilised these approaches to inform subsequent healthcare research and as a professional training tool to improve patient experience in a healthcare setting. We add to emerging literature to outline the benefits of these approaches in supporting research and training in healthcare settings, with a focus towards the co-produced foundations of these approaches. We demonstrate how such approaches can be utilised to capture different forms of voices, experiences and perspectives to help inform healthcare research and training, rooted in the lived experience of individuals who are directly involved in the creative process of developing personas via storytelling. These approaches challenge the listener to “walk in someone else’s shoes”, using their own homes and lives as a theatrical set in which to envisage someone else’s story, involving the listener in the creative process through (re)imagining the stories and experiences of the characters. Greater use of immersive, co-produced participatory art-based approaches should be used in PPIE to inform research and training in healthcare settings as a means of centring those with lived experience through co-production. Involving those with lived experience, particularly from groups who are traditionally excluded from research, via a process which is based on co-creation and co-production, reorientates the researcher-participant dynamic to fully centre those involved in the research at the heart of the tools used to guide health and healthcare research. In this way, it may also aid in trust and relationship building between institutions and communities in a way which is focused around positive, creative methods to aid health research and healthcare processes. Such approaches may help to break down barriers between academic institutions, healthcare sites and communities.
Embracing Myeloma Chimeric Antigen Receptor-T: From Scientific Design to Clinical Impact
Authors: Hosoya Hitomi , Rodriguez-Otero Paula , Sidana Surbhi , Borrello Ivan M.
Published: June 2023

Despite recent advancement of treatment strategies in multiple myeloma (MM), patients with relapsed/refractory MM disease, particularly after triple-class refractoriness, continue to have poor prognosis. Chimeric antigen receptor (CAR-T) cells were developed and applied to improve outcomes in this setting, and two products, idecabtagene vicleucel and ciltacabtagene autoleucel, both targeting B-cell maturation antigen, have been approved by the Food and Drug Administration in the United States and European Medicines Agency in Europe. Both have shown unprecedented clinical outcomes with high response rate and prolonged progression-free survival and overall survival in this patient population with grim prognosis. Currently, further investigations are ongoing for CAR-T targeting different tumor antigens such as G protein–coupled receptor, class C, group 5, member D or with different combinations of intracellular signaling domains, as well as fourth-generation CAR-T with antigen-unrestricted inducible cytokines. Although CAR-T therapies hold hopes and enthusiasm from the myeloma community, several hurdles remain before these treatments become available for all patients in need. These barriers include CAR-T-cell manufacturing availability, access to administering centers, financial cost, caregivers' availability, and socioeconomic and racial disparities. Expanding clinical trial eligibility criteria and real-world data collection and analysis is crucial to understand the efficacy and safety of CAR-T in the patient cohort who tends to be excluded from current trials.
Anti-tumor activity of sunvozertinib in NSCLC with EGFR sensitizing mutations after failure of EGFR TKI treatment.
Authors: Yang James Chih-Hsin , Xu Yan , Huang Wen-Tsung , Su Wu-Chou , Gao Bo , Lee Chee Khoon , Fang Jian , Yu Wenlei , Wang Mengzhao , Janne Pasi A.
Published: June 2023

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Background: Sunvozertinib is a rationally designed, irreversible EGFR inhibitor targeting various EGFR mutations with wild-type EGFR selectivity. Clinical studies have showed its superior efficacy than current available therapies and favorable safety profile for treating NSCLC patients with EGFR exon20 mutations. Here we reported its anti-tumor activity in patients with EGFR sensitizing mutations (EGFRm) who failed from standard EGFR TKI treatment. Methods: This is a pooled analysis of three clinical studies in patients with EGFRm or HER2m NSCLC: WU-KONG1 (multinational phase I/II study, NCT03974022), WU-KONG2 (phase I study in China, CTR20192097), and WU-KONG15 (phase II study in China, NCT05559645). Patients were enrolled to receive sunvozertinib once daily at defined doses until discontinuation criteria were met. Patients who had EGFRm NSCLC, at least one measurable lesion at baseline, received at least one dose of sunvozertinib, and underwent at least one post-treatment RECIST assessment were evaluable for efficacy analysis. Patients with EGFRm or HER2m NSCLC who failed from standard systemic therapies and received at least one dose of sunvoertinib were included in the safety analysis. Results: As of October 17, 2022, a total of 32 patients who met efficacy evaluable criteria were included in the analysis. The doses of sunvozertinib ranged from 50 mg - 400 mg. Baseline characteristics: median age was 64.5 years old; 68.8% (22/32) were female; 75.0% (24/32) ECOG PS was 1; 34.4% (11/32) had more than three metastatic sites; 43.8% (14/32) had baseline brain metastases. Patients were heavily pretreated, with a median of 5 lines (range 1 - 16) of prior therapies. All patients had been treated with at least one type of EGFR TKI, including 68.8% (22/32) had been treated with a 3rd generation EGFR TKI. The majority of patients (29/32, 90.6%) had also been treated with chemotherapy. Anti-tumor activity was observed starting from 50 mg. Per investigators’ assessment, the best objective response rate (BoR) was 21.9% (7/32). Anti-tumor activity was observed regardless of T790M mutation status. At the data cutoff date, the median duration of response and progression-free survival were 4.0 months and 5.9 months, respectively. Sunvozertinib was well-tolerated across all dose levels. The safety profile was similar to what has been previously reported. The longest treatment duration was more than 35 months (still ongoing). Conclusions: Sunvozertinib monotherapy demonstrated promising anti-tumor activity in heavily pretreated EGFRm NSCLC patients. Further clinical evaluation of sunvozertinib in this patient population is warranted. The updated data will be presented at the conference. Clinical trial information: NCT05559645 NCT03974022 and CTR20192097 .
Aging through Precarious Time: Maintenance and Milling in The Cost of Living and Weather
Authors: Kruger Katherine
Published: June 2023

Changes to working life and retirement are reshaping temporalities of aging. This essay identifies a growing interest by women writers in the narrative possibilities these changes present. Examining the relation between narrative form, aging, and precarious work in Deborah Levy's The Cost of Living (2018) and Jenny Offill's Weather (2020), this essay argues that contemporary narratives of midlife aging offer evidence of new and different conceptions and representations of time, whereby time is shaped by the elongated precarity of care and work. The argument builds on work by Lauren Berlant (2011), Elizabeth Povinelli (2011), and Lisa Baraitser (2017) that claims that the challenges of the twenty-first century demand that we reimagine future time through the lens of endurance and finds a model for endurance in the time frames of maintenance and milling proposed in The Cost of Living and Weather.
Contradictory Late Styles in Djuna Barnes's Poetic Cycles, 1969–82
Authors: French Jade Elizabeth
Published: June 2023

Focusing on examples of Djuna Barnes's late published poetry—“Quarry” (1969), “Rite of Spring” (1982), and Creatures in an Alphabet (1982)—this article considers the contradictory ways these poems engage with theories of late style. Barnes's late output offers a unique and somewhat ambivalent case study for examining how the privileging of difficulty and discordance are met and informed by the lived realities of aging and longevity. Paying attention to the publication history of each poem, this article first examines Barnes's redrafting process for “Rite of Spring,” which has been recently reassessed as a conscious, avant-garde experiment, one this article suggests embraced lateness and continuation as a method. Second, the article considers “Quarry” and Barnes's correspondence with publishers Faber and Faber to examine her attitude toward a seemingly finalized poem. Third, this article turns to Creatures in an Alphabet as an example of a supposedly completed project that was left unendorsed by Barnes and the tensions inherent in trying to read a late style into its material. Overall, I suggest that the revisionary nature of Barnes's poetry and its unfinishing state is a late style process, which represents a formal experiment, a creative experience informed by aging, and an example of the cultural investment critics have made in her late works.
The Aesthetics of Aging: Visual Strategies and Narrative Form in Tanizaki'sDiary of a Mad Old Man
Authors: Crossley Alice
Published: June 2023

This essay reads Tanizaki Jun'ichirō’s controversial novel Diary of a Mad Old Man (1961) for its contribution to discourses about aging masculinity and male sexuality in later life. The Diary meditates on the mental and physical vicissitudes of aging masculinity, arousal, control, and impotence, focused through the fictional diarist Utsugi's physical ailments and expression of libidinal intensities. The article argues for Tanizaki's depiction of male aging as an exercise in both disenfranchisement and agentive potential. First, it reads the aging process through aesthetic and visual strategies, which magnify the protagonist's cultivation of masochistic pleasure as a specific correlative of aging. The article demonstrates that the narrative uses the rhetoric of cinema and photography—central terms of reference in Tanizaki's work—to frame Utsugi's experiences of old age, and inform his erotic fantasies as stylized, staged performances. In conjunction with these visual modes, the novel draws on traditional Japanese aesthetics to conceptualize the potential affect and perverse empowerment of the aging experience. Second, it addresses the implications of narrative form, as the self-reflexive, first-person diary prioritizes the subjectivity of Utsugi's male old age, while the novel's final pages interrupt and thus alter the diary's significance as a private account of self-expression.
GI Photos of Calcutta: Toward a Vernacular Understanding of War
Authors: Mallik Santasil
Published: June 2023

During World War II, more than a hundred thousand US soldiers, popularly known as GIs, camped in Calcutta, India, to steer the Eastern Front war against the Imperial Japanese Army in the China-Burma-India theater. The port city became a strategically relevant transit hub for the soldiers to airlift food and military resources, alongside channeling information to war zones. But it also acted as a site for the rest and recreation of the soldiers. With higher salaries and added scope for leisure in Calcutta, the pervasive presence of the GIs introduced a new orientation of military relationship with the public—more cordial, touristic, and commercially transactional than the British officials. Military photographer Clyde Waddell captured the recreational activities of GIs in the streets of Calcutta at their behest and self-published sixty photographs in 1946. Though the images depict everyday scenes in the colonial city, their thematic elements and semiotics betray the ideological designs of the US Army in an era of changing global equations. Waddell's images inhabit a curious location between wartime reportage and personal memorabilia. This article undertakes a semiotic reading of such photographs by Waddell to situate the complex location of the American GIs in the erstwhile capital city of the disintegrating British colony.