bluuebunny/crossref_metadata_2025_split huggingface dataset:
The prognostic value of IPI in patients with primary breast lymphoma, a multicenter retrospective study
Authors: Feng Kexin , Zhao Shuangtao , Shang Qingyao , Qiao Guangdong , Liu Jiaxiang , Yang Chenxuan , Wei Ya , Li Yalun , Ren Fei , Xuan Lixue , Wang Xiang , Wang Xin 
Published: November 2022

Abstract
Background
Due to the rarity of PBL and the lack of large-scale studies, the prognostic value of IPI in PBL was controversial. Especially in the rituximab era, the ability of IPI to stratify prognosis in patients receiving immunochemotherapy was severely reduced. Then revised IPI (R-IPI) and National Comprehensive Cancer Network IPI (NCCN-IPI) were introduced. The present study aimed to evaluate the prognostic value of IPI and the other IPIs in patients with PBL in a Chinese population.

Methods
We performed a multicenter retrospective study of 71 patients with PBL from 3 institutions in China. The Kaplan–Meier method and log-rank tests were used for the survival analysis. Cox regression analysis was performed to evaluate the prognostic factors. Subgroup analysis was performed to assess the prognostic significance of IPI scores, R-IPI scores, and NCCN-IPI scores.

Results
The median follow-up was 4.7 years (0.7–21.8 years). The 5-year progression-free survival (PFS) and overall survival (OS) rates were 90.2% and 96.3%. In the multivariate analysis, only IPI scores and radiotherapy were significantly associated with OS and PFS (P < 0.05). Applying the R-IPI in our patient cohort indicates a significant difference in PFS between the two groups of R-IPI (P = 0.034) but not for OS (P = 0.072). And the NCCN-IPI was prognostic for OS (P = 0.025) but not for PFS (P = 0.066). Subgroup analyses of IPI showed that survival analysis of IPI scores for the PFS and OS of patients using rituximab were not significantly different (P > 0.05).

Conclusions
Our study confirms the prognostic value of IPI in patients with PBL, but the predictive value of IPI proved to be relatively low with the addition of the rituximab. The R-IPI and NCCN-IPI can accurately assess the high and low-risk groups of PBL patients but were insufficient to evaluate the intermediate risk group.
A literature review exploring how health systems respond to acute shocks in fragile and conflict-affected countries
Authors: Thu Kyaw Myat , Bernays Sarah , Abimbola Seye 
Published: November 2022

AbstractUnderstanding how health systems respond to shocks has become a pressing need to strengthen response efforts. With already fragmented and disrupted health services, fragile and conflict affected [FCA] countries are more vulnerable to shocks. Previous studies have focused more on conceptualizing health system resilience rather than how health systems [especially in FCA countries] respond to or are resilient to acute shocks. To understand how health systems in FCA countries respond to the shocks and what influence their responses, we conducted a review of the literature published between January 2011 and September 2021 on health system responses to acute shocks in FCA countries. We searched Medline, Embase, Scopus, Jester and Google Scholar – 60 empirical studies in FCA countries on response to sudden, extreme, and unanticipated shocks were included in the review. We found that health systems in FCA countries responded to acute shock using absorptive, adaptive, or transformative capacities. These capacities were mediated by four dimensions of context; knowledge, uncertainties, interdependence, and legitimacy. In addition, we identified the cross-cutting role of community involvement [and its self-evolving nature], frontline workers, and leadership capacity. To our knowledge, this is among the first reviews that focus on FCA country health systems responses to acute shock. By highlighting enabling and constraining factors to each type of capacity, this study provides important lessons and practical strategies from FCA countries on how to absorb, adapt and transform in response to acute shocks – thus promoting health system resilience globally.
Preclinical evaluation of combination nemtabrutinib and venetoclax in chronic lymphocytic leukemia
Authors: Muhowski Elizabeth M. , Ravikrishnan Janani , Gordon Britten , Yu Lianbo , Misra Shrilekha , Walker Brandi , Eathiraj Sudharshan , Sampath Deepa , Rogers Kerry A. , Byrd John C. , Woyach Jennifer A. 
Published: November 2022

AbstractInhibitors of B cell receptor (BCR) signaling such as the Bruton’s tyrosine kinase (BTK) inhibitors are effective therapeutics for chronic lymphocytic leukemia (CLL). The first-in-class covalent BTK inhibitor, ibrutinib, produces durable responses in most CLL patients; however, complete responses are only observed in a minority of patients. B cell lymphoma 2 (BCL2), an anti-apoptotic protein that contributes to CLL cell survival, has also been investigated as a therapeutic target. The BCL2 inhibitor venetoclax is effective in patients with CLL and can produce undetectable minimal residual disease, allowing discontinuation of therapy. In combination, ibrutinib and venetoclax have shown preclinical synergy and clinical efficacy. Nemtabrutinib is a next generation, reversible inhibitor of BTK that potently inhibits BCR signaling in treatment-naïve and ibrutinib-refractory CLL cells ex vivo. The clinical efficacy of combining BTK inhibitors with BCL2 inhibitors motivated us to evaluate the novel combination of nemtabrutinib and venetoclax. In vitro studies show that nemtabrutinib and venetoclax are not antagonistic to each other. In an adoptive transfer CLL mouse model, mice treated with nemtabrutinib and venetoclax had prolonged survival compared to mice treated with ibrutinib and venetoclax. Our preclinical studies further validate the combination of BTK inhibitors with venetoclax and justify further investigation of combining nemtabrutinib with venetoclax in CLL.
Nitrogen and sulfur-doped carbon quantum dots as fluorescent nanoprobes for spectrofluorimetric determination of olanzapine and diazepam in biological fluids and dosage forms: application to content uniformity testing
Authors: Magdy Galal , Said Noura , El-Domany Ramadan A. , Belal Fathalla 
Published: November 2022

AbstractA validated, sensitive, and simple spectrofluorimetric method was developed for the analysis of two important CNS-acting drugs, olanzapine and diazepam, in their commercial tablets without the need for any pretreatment steps. The developed method relied on the quantitative quenching effect of each of olanzapine and diazepam on the native fluorescence of nitrogen and sulfur-doped carbon quantum dots (NS@CQDs). NS@CQDs were prepared from thiosemicarbazide and citric acid by a facile one-pot hydrothermal technique. The synthesized NS@CQDs were characterized by different spectroscopic and microscopic techniques. NS@CQDs produced a maximum emission peak at 430 nm using 360 nm as an excitation wavelength. Calibration curves showed a good linear regression over the range of 5.0–200.0 and 1.0–100.0 μM with detection limits of 0.68 and 0.29 μM for olanzapine and diazepam, respectively. The adopted method was used for the determination of the investigated drugs in their tablets with high % recoveries (98.84–101.70%) and low % RSD values (< 2%). As diazepam is one of the most commonly abused benzodiazepines, the developed method was successfully applied for its determination in spiked human plasma with high % recoveries and low % RSD values, providing further insights for monitoring its potential abuse. The quenching mechanism was also studied and confirmed to be through dynamic and static quenching for olanzapine and diazepam, respectively. Due to the high selectivity and sensitivity, content uniformity testing of low-dose tablets was successfully performed by applying the United States Pharmacopoeia guidelines. The method's validation was performed in compliance with ICHQ2 (R1) recommendations.
Cryopreservation does not change the performance and characteristics of allogenic mesenchymal stem cells highly over-expressing a cytoplasmic therapeutic transgene for cancer treatment
Authors: Ho Yoon Khei , Loke Kin Man , Woo Jun Yung , Lee Yee Lin , Too Heng-Phon 
Published: November 2022

Abstract
Background
Mesenchymal stem cells (MSCs) driven gene directed enzyme prodrug therapy is a promising approach to deliver therapeutic agents to target heterogenous solid tumours. To democratize such a therapy, cryopreservation along with cold chain transportation is an essential part of the logistical process and supply chain. Previously, we have successfully engineered MSCs by a non-viral DNA transfection approach for prolonged and exceptionally high expression of the fused transgene cytosine deaminase, uracil phosphoribosyl transferase and green fluorescent protein (CD::UPRT::GFP). The aim of this study was to determine the effects of cryopreservation of MSCs engineered to highly overexpress this cytoplasmic therapeutic transgene.

Methods
Modified MSCs were preserved in a commercially available, GMP-grade cryopreservative—CryoStor10 (CS10) for up to 11 months. Performance of frozen-modified MSCs was compared to freshly modified equivalents in vitro. Cancer killing potency was evaluated using four different cancer cell lines. Migratory potential was assessed using matrigel invasion assay and flow cytometric analysis for CXCR4 expression. Frozen-modified MSC was used to treat canine patients via intra-tumoral injections, or by intravenous infusion followed by a daily dose of 5-flucytosine (5FC).

Results
We found that cryopreservation did not affect the transgene expression, cell viability, adhesion, phenotypic profile, and migration of gene modified canine adipose tissue derived MSCs. In the presence of 5FC, the thawed and freshly modified MSCs showed comparable cytotoxicity towards one canine and three human cancer cell lines in vitro. These cryopreserved cells were stored for about a year and then used to treat no-option-left canine patients with two different types of cancers and notably, the patients showed progression-free interval of more than 20 months, evidence of the effectiveness in treating spontaneously occurring cancers.

Conclusion
This study supports the use of cryopreserved, off-the-shelf transiently transfected MSCs for cancer treatment.
MDDI-SCL: predicting multi-type drug-drug interactions via supervised contrastive learning
Authors: Lin Shenggeng , Chen Weizhi , Chen Gengwang , Zhou Songchi , Wei Dong-Qing , Xiong Yi 
Published: November 2022

AbstractThe joint use of multiple drugs may cause unintended drug-drug interactions (DDIs) and result in adverse consequence to the patients. Accurate identification of DDI types can not only provide hints to avoid these accidental events, but also elaborate the underlying mechanisms by how DDIs occur. Several computational methods have been proposed for multi-type DDI prediction, but room remains for improvement in prediction performance. In this study, we propose a supervised contrastive learning based method, MDDI-SCL, implemented by three-level loss functions, to predict multi-type DDIs. MDDI-SCL is mainly composed of three modules: drug feature encoder and mean squared error loss module, drug latent feature fusion and supervised contrastive loss module, multi-type DDI prediction and classification loss module. The drug feature encoder and mean squared error loss module uses self-attention mechanism and autoencoder to learn drug-level latent features. The drug latent feature fusion and supervised contrastive loss module uses multi-scale feature fusion to learn drug pair-level latent features. The prediction and classification loss module predicts DDI types of each drug pair. We evaluate MDDI-SCL on three different tasks of two datasets. Experimental results demonstrate that MDDI-SCL achieves better or comparable performance as the state-of-the-art methods. Furthermore, the effectiveness of supervised contrastive learning is validated by ablation experiment, and the feasibility of MDDI-SCL is supported by case studies. The source codes are available athttps://github.com/ShenggengLin/MDDI-SCL.
Multi-locus sequence analysis reveals great genetic diversity among Mycoplasma capricolum subsp. capripneumoniae strains in Asia
Authors: Akhtar Arooba , Boissière Anne , Hao Huafang , Saeed Muhammad , Dupuy Virginie , Exbrayat Antoni , Khan Farhan Anwar , Chu Yuefeng , Manso-Silván Lucía 
Published: November 2022

AbstractMulti-Locus Sequence Analysis (MLSA) of Mycoplasma capricolum subsp. capripneumoniae (Mccp) strains from Asia revealed unforeseen diversity and a central position for genotyping groups representing strains from Central/East Asia, suggesting a possible origin of contagious caprine pleuropneumonia in this continent. A better assessment of the emergence, diversity and distribution of Mccp in Asia and Africa calls for renewed efforts to dramatically enlarge the sample of strains. Availability and affordability in the field, added to superior typeability (directly from poor samples) and high stability, discriminatory power and concordance with epidemiological and phylogenetic analyses, make MLSA an excellent tool for such investigations.
Deep reinforcement learning-based beam training with energy and spectral efficiency maximisation for millimetre-wave channels
Authors: Narengerile  , Thompson John , Patras Paul , Ratnarajah Tharmalingam 
Published: November 2022

AbstractThe millimetre-wave (mmWave) spectrum has been investigated for the fifth generation wireless system to provide greater bandwidths and faster data rates. The use of mmWave signals allows large-scale antenna arrays to concentrate the radiated power into narrow beams for directional transmission. The beam alignment at mmWave frequency bands requires periodic training because mmWave channels are sensitive to user mobility and environmental changes. To benefit from machine learning technologies that will be used to build the sixth generation (6G) communication systems, we propose a new beam training algorithm via deep reinforcement learning. The proposed algorithm can switch between different beam training techniques according to the changes in the wireless channel such that the overall beam training overhead is minimised while achieving good performance of energy efficiency or spectral efficiency. Further, we develop a beam training strategy which can maximise either energy efficiency or spectral efficiency by controlling the number of activated radio frequency chains based on the current channel conditions. Simulation results show that compared to baseline algorithms, the proposed approach can achieve higher energy efficiency or spectral efficiency with lower training overhead.
Socio-demographic, behavioural and clinical factors influencing control of diabetes and hypertension in urban Mysore, South India: a mixed-method study conducted in 2018
Authors: Dey Sudeshna , Mukherjee Aparna , Pati Manoj Kumar , Kar Arin , Ramanaik Satyanarayana , Pujar Ashwini , Malve Vidyacharan , Mohan H. L. , Jayanna Krishnamurthy , N Swaroop 
Published: November 2022

Abstract
Background
Inadequate control of diabetes and hypertension is a major concern in India because of rising mortality and morbidity. Few studies in India have explored factors that influence control of diabetes and hypertension. The current study aimed to improve the understanding of multifactorial influence on the control of diabetes and hypertension among patients in Primary Health Care Settings(PHC) of urban Karnataka.

Methods
We used a mixed-method study design, within a project aiming to improve non-communicable disease (NCD) continuum of care across PHC in Mysore city, India, conducted in 2018. The quantitative study was conducted among 399 patients with diabetes and/or hypertension and a logistic regression model was used to assess the factors responsible for biological control levels of diabetes and hypertension measured through Glycated Haemoglobin(HbA1c) and blood pressure. Further, in-depth interviews(IDI) were conducted among these patients and the counsellors at PHCs to understand the barriers and enablers for better control.

Result
The quantitative assessment found odds of poor control amongst diabetics’ increased with older age, longer duration of disease, additional chronic conditions, and tobacco consumption. For hypertensives, odds of poor control increased with higher body mass index(BMI), alcohol consumption, and belongingness to lower social groups. These findings were elaborated through qualitative assessment which found that the control status was affected by stress as a result of family or financial worries. Stress, poor lifestyle, and poor health-seeking behaviour interplay with other factors like diet and exercise leading to poor control of diabetes and hypertension.

Conclusion
A better understanding of determinants associated with disease control can assist in designing focused patient outreach plans, customized communication strategies, need-based care delivery plans, and specific competency-based capacity-building models for health care workers. Patient-centric care focusing on biological, social and behavioural determinants is pivotal for appropriate management of NCDs at community level in low-middle income countries.
SGOL2 is a novel prognostic marker and fosters disease progression via a MAD2-mediated pathway in hepatocellular carcinoma
Authors: Hu Qingqing , Liu Qiuhong , Zhao Yalei , Zhang Lingjian , Li Lanjuan 
Published: November 2022

Abstract
Background
Shugoshin-like protein 2 (SGOL2) is a centromeric protein that ensures the correct and orderly process of mitosis by protecting and maintaining centripetal adhesions during meiosis and mitosis. Here, we examined the potential role of SGOL2 in cancers, especially in hepatocellular carcinoma (HCC).

Methods
One hundred ninety-nine normal adjacent tissues and 202 HCC samples were collected in this study. Human HCC cells (SK-HEP-1 and HEP-3B) were employed in the present study. Immunohistochemistry, immunofluorescence, western blot, Co-Immunoprecipitation technique, and bioinformatic analysis were utilized to assess the role of SGOL2 in HCC development process.

Results
Overexpression of SGOL2 predicted an unfavorable prognosis in HCC by The Cancer Genome Atlas database (TCGA), which were further validated in our two independent cohorts. Next, 47 differentially expressed genes positively related to both SGOL2 and MAD2 were identified to be associated with the cell cycle. Subsequently, we demonstrated that SGOL2 downregulation suppressed the malignant activities of HCC in vitro and in vivo. Further investigation showed that SGOL2 promoted tumor proliferation by regulating MAD2-induced cell-cycle dysregulation, which could be reversed by the MAD2 inhibitor M2I-1. Consistently, MAD2 upregulation reversed the knockdown effects of SGOL2-shRNA in HCC. Moreover, we demonstrated that SGOL2 regulated MAD2 expression level by forming a SGOL2-MAD2 complex, which led to cell cycle dysreuglation of HCC cells.

Conclusion
SGOL2 acts as an oncogene in HCC cells by regulating MAD2 and then dysregulating the cell cycle, providing a potential therapeutic target in HCC.
Impact of differential item functioning on group score reporting in the context of large-scale assessments
Authors: Joo Sean , Ali Usama , Robin Frederic , Shin Hyo Jeong 
Published: November 2022

AbstractWe investigated the potential impact of differential item functioning (DIF) on group-level mean and standard deviation estimates using empirical and simulated data in the context of large-scale assessment. For the empirical investigation, PISA 2018 cognitive domains (Reading, Mathematics, and Science) data were analyzed using Jackknife sampling to explore the impact of DIF on the country scores and their standard errors. We found that the countries that have a large number of DIF items tend to increase the difference of the country scores computed with and without the DIF adjustment. In addition, standard errors of the country score differences also increased with the number of DIF items. For the simulation study, we evaluated bias and root mean squared error (RMSE) of the group mean and standard deviation estimates using the multigroup item response theory (IRT) model to explore the extent to which DIF items create a bias of the group mean scores and how effectively the DIF adjustment corrects the bias under various conditions. We found that the DIF adjustment reduced the bias by 50% on average. The implications and limitations of the study are further discussed.
High Diagnostic Accuracy of Epigenetic Imprinting Biomarkers in Thyroid Nodules
Authors: Xu Huixiong , Zhang Yifeng , Wu Hongxun , Zhou Ning , Li Xing , Pineda John P. , Zhu Yun , Fu Huijun , Ying Ming , Yang Shufang , Bao Jiandong , Yang Lulu , Zhang Bingjie , Guo Lehang , Sun Liping , Lu Feng , Wang Hanxiang , Huang Ying , Zhu Tiantong , Wang Xiaonan , Wei Qing , Sheng Chunjun , Qu Shen , Lv Zhongwei , Xu Dong , Li Qian , Dong Yongling , Qin Jianwu , Cheng Tong , Xing Mingzhao 
Published: November 2022

PURPOSE To explore the novel diagnostic value of epigenetic imprinting biomarkers in thyroid nodules. PATIENTS AND METHODS A total of 550 patients with fine-needle aspiration (FNA)–evaluated and histopathologically confirmed thyroid nodules were consecutively recruited from eight medical centers. Quantitative chromogenic imprinted gene in situ hybridization (QCIGISH) was used to assess the allelic expression of imprinted genes SNRPN and HM13, on the basis of which a diagnostic grading model for thyroid nodules was developed. The model was retrospectively trained on 124 postsurgical thyroid samples, optimized on 32 presurgical FNA samples, and prospectively validated on 394 presurgical FNA samples. Blinded central review–based cytopathologic and histopathologic diagnoses were used as the reference standard. RESULTS For thyroid malignancy, the QCIGISH test achieved an overall diagnostic sensitivity of 100% (277/277), a specificity of 91.5% (107/117; 95% CI, 86.4 to 96.5), a positive predictive value (PPV) of 96.5% (95% CI, 94.4 to 98.6), and a negative predictive value (NPV) of 100% in the prospective validation, with a diagnostic accuracy of 97.5% (384/394; 95% CI, 95.9 to 99.0). QCIGISH demonstrated a PPV of 97.8% (95% CI, 94.7 to 100) and NPV of 100%, with a diagnostic accuracy of 98.2% (111/113; 95% CI, 95.8 to 100), for indeterminate Bethesda III-V thyroid nodules. QCIGISH demonstrated a PPV of 96.6% (95% CI, 91.9 to 100) and a NPV of 100%, with a diagnostic accuracy of 97.5% (79/81; 95% CI, 94.2 to 100), for Bethesda III-IV. For Bethesda VI, QCIGISH showed a 100% (184/184) accuracy. CONCLUSION This imprinting biomarker-based test can effectively distinguish malignant from benign thyroid nodules. The high PPV and NPV make the test both an excellent rule-in and rule-out diagnostic tool. With such a diagnostic performance and its technical simplicity, this novel thyroid molecular test is clinically widely applicable.