bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clonal phylogeny and evolution of critical cytogenetic aberrations in multiple myeloma at single-cell level by QM-FISH
Authors: Yan Yuting , Qin Xiaoqi , Liu Jiahui , Fan Huishou , Yan Wenqiang , Liu Lanting , Du Chenxing , Yu Zhen , Xu Yan , Hao Mu , Deng Shuhui , Sui Weiwei , Lyu Rui , Liu Wei , Wang Qi , Zou Dehui , Hu Linping , Wang Jianxiang , Tai Yu-Tzu , Anderson Kenneth C. , Zhang Lei , Cheng Tao , Zetterberg Anders , Munshi Nikhil C. , Qiu Lugui , An Gang 
Published: October 2021

Abstract
Single-cell analysis is of significant importance in delineating the exact phylogeny of the subclonal population and in discovering subtle diversification. So far, studies of intratumor heterogeneity and clonal evolution in multiple myeloma (MM) were largely focused on the bulk tumor population level. We performed quantitative multigene fluorescence in situ hybridization (QM-FISH) in 129 longitudinal samples of 57 MM patients. All the patients had newly diagnosed and relapsed paired samples. An expanded cohort of 188 MM patients underwent conventional FISH (cFISH) to validate the cytogenetic evolution in bulk tumor level. Forty-three of 57 patients (75.4%) harbored 3 or 4 cytogenetic clones at diagnosis. We delineated the phylogeny of the subclonal tumor population and derived the evolutionary architecture in each patient. Patients with clonal stabilization had a significantly improved overall survival (OS) than those with other evolutionary patterns (median OS, 71.2 months vs 39.7 months vs 35.2 months vs 25.5 months, for stable, differential, branching, and linear patterns, respectively; P = .001). A high degree of consistency and complementarity across QM-FISH and cFISH was observed in the evaluation of cytogenetic evolution patterns in MM. Survival after relapse was greater influenced by the presence of high-risk aberrations at relapse (hazard ratio = 2.07) rather than present at diagnosis (hazard ratio = 1.55). This study shows that QM-FISH is a valuable tool to elucidate the clonal architecture at the single-cell level. Clonal evolution pattern is of prognostic significance, highlighting the need for repeated cytogenetic evaluation in relapsed MM.
Modulating endothelial cells with EGFL7 to diminish aGVHD after allogeneic bone marrow transplantation in mice
Authors: Dorrance Adrienne M. , Moutuou Moutuaata M. , Goda Chinmayee , Sell Natalie E. , Kalyan Sonu , Karunasiri Malith , Kulkarni Rohan , Goulard Marie , Kolovich Sofia , Rudich Alexander , Naumann Eric , Ackaoui Antoine , Bigras Charles-Etienne , Daudelin Francis , Garzon Ramiro , Ranganathan Parvathi , Guimond Martin 
Published: October 2021

Abstract
Acute graft-versus-host disease (aGVHD) is the second most common cause of death after allogeneic hematopoietic stem cell transplantation (allo-HSCT), underscoring the need for novel therapies. Based on previous work that endothelial cell dysfunction is present in aGVHD and that epidermal growth factor-like domain 7 (EGFL7) plays a significant role in decreasing inflammation by repressing endothelial cell activation and T-cell migration, we hypothesized that increasing EGFL7 levels after allo-HSCT will diminish the severity of aGVHD. Here, we show that treatment with recombinant EGFL7 (rEGFL7) in 2 different murine models of aGVHD decreases aGVHD severity and improves survival in recipient mice after allogeneic transplantation with respect to controls without affecting graft-versus-leukemia effect. Furthermore, we showed that rEGFL7 treatment results in higher thymocytes, T, B, and dendritic cell counts in recipient mice after allo-HSCT. This study constitutes a proof of concept of the ability of rEGFL7 therapy to reduce GHVD severity and mortality after allo-HSCT.
Retrospective epidemiological study of urolithiasis in western Algeria over a period of 50 years
Authors: Sbahi Khayra , Kacem Brahim , Talhi Randa , Azaiz Aicha , Attar Abderahmane , Addou Ahmed 
Published: October 2021

Abstract
Background
Urolithiasis is a pathology that changes with time and with the evolution of human societies. The prevalence of this pathology has gradually increased during the last decades, especially because of dietary changes.

Methods
This work is a retrospective descriptive epidemiological study of the temporal type carried out at the level of the urology service of the University Hospital Center of Oran between the first January 1965 and December 31, 2014. The objectives of this work are to study the epidemiological profile of urolithiasis and to determine the evolutionary trend of the disease over time.

Results
This study confirms some current data in the direction of an increase in surgical activity concerning the treatment of urinary stones. The analysis over time shows us a significant decrease (p < 0.01) in the male predominance between 1965 and 2014 with a M/F ratio which decreased from 3.09 to 1.82, as well as an increase in the average age, rising from 28.8 years in the period 1965–1974 to 48.3 years between 2005 and 2014.

Conclusion
The analysis of epidemiological data is essential to better evaluate the evolution of the urolithiasis disease, which was affirmed in our study, where a constant evolution of the characteristics of the disease was revealed, testifying the change of the socio-economic level in Algeria.
CL-ACP: a parallel combination of CNN and LSTM anticancer peptide recognition model
Authors: Wang Huiqing , Zhao Jian , Zhao Hong , Li Haolin , Wang Juan 
Published: October 2021

AbstractBackgroundAnticancer peptides are defence substances with innate immune functions that can selectively act on cancer cells without harming normal cells and many studies have been conducted to identify anticancer peptides. In this paper, we introduce the anticancer peptide secondary structures as additional features and propose an effective computational model, CL-ACP, that uses a combined network and attention mechanism to predict anticancer peptides.ResultsThe CL-ACP model uses secondary structures and original sequences of anticancer peptides to construct the feature space. The long short-term memory and convolutional neural network are used to extract the contextual dependence and local correlations of the feature space. Furthermore, a multi-head self-attention mechanism is used to strengthen the anticancer peptide sequences. Finally, three categories of feature information are classified by cascading. CL-ACP was validated using two types of datasets, anticancer peptide datasets and antimicrobial peptide datasets, on which it achieved good results compared to previous methods. CL-ACP achieved the highest AUC values of 0.935 and 0.972 on the anticancer peptide and antimicrobial peptide datasets, respectively.ConclusionsCL-ACP can effectively recognize antimicrobial peptides, especially anticancer peptides, and the parallel combined neural network structure of CL-ACP does not require complex feature design and high time cost. It is suitable for application as a useful tool in antimicrobial peptide design.
Measuring the ratio of femoral vein diameter to femoral artery diameter by ultrasound to estimate volume status
Authors: Ma Zhihang , Gai Jiaxin , Sun Yinghan , Bai Yunpeng , Cai Hongyi , Wu Lei , Sun Lixiu , Liu Junyan , Xue Li , Liu Bingchen 
Published: October 2021

Abstract
Background
Currently, the accepted effective method for assessing blood volume status, such as measuring central venous pressure (CVP) and mean pulmonary artery pressure (mPAP), is invasive. The purpose of this study was to explore the feasibility and validity of the ratio of the femoral vein diameter (FVD) to the femoral artery diameter (FAD) for predicting CVP and mPAP and to calculate the cut-off value for the FVD/FAD ratio to help judge a patient’s fluid volume status.

Methods
In this study, 130 patients were divided into two groups: in group A, the FVD, FAD, and CVP were measured, and in group B, the FVD, FAD, and mPAP were measured. We measured the FVD and FAD by ultrasound. We monitored CVP by a central venous catheter and mPAP by a Swan-Ganz floating catheter. Pearson correlation coefficients were calculated. The best cut-off value for the FVD/FAD ratio for predicting CVP and mPAP was obtained according to the receiver operating characteristic (ROC) curve.

Results
The FVD/FAD ratio was strongly correlated with CVP (R = 0.87, P < 0.0000) and mPAP (R = 0.73, P < 0.0000). According to the ROC curve, an FVD/FAD ratio ≥ 1.495 had the best test characteristics to predict a CVP ≥ 12 cmH2O, and an FVD/FAD ratio ≤ 1.467 had the best test characteristics to predict a CVP ≤ 10 cmH2O. An FVD/FAD ratio ≥ 2.03 had the best test characteristics to predict an mPAP ≥ 25 mmHg. According to the simple linear regression curve of the FVD/FAD ratio and CVP, when the predicted CVP ≤ 5 cmH2O, the FVD/FAD ratio was ≤ 0.854.

Conclusion
In this study, the measurement of the FVD/FAD ratio obtained via ultrasound was strongly correlated with CVP and mPAP, providing a non-invasive method for quickly and reliably assessing blood volume status and providing good clinical support.
Optimising personal continuity for older patients in general practice: a study protocol for a cluster randomised stepped wedge pragmatic trial
Authors: Groot Lex J. J. , Schers Henk J. , Burgers Jako S. , Schellevis Francois G. , Smalbrugge Martin , Uijen Annemarie A. , van de Ven Peter M. , van der Horst Henriëtte E. , Maarsingh Otto R. 
Published: October 2021

Abstract
Background
Continuity of care, in particular personal continuity, is a core principle of general practice and is associated with many benefits such as a better patient-provider relationship and lower mortality. However, personal continuity is under pressure due to changes in society and healthcare. This affects older patients more than younger patients. As the number of older patients will double the coming decades, an intervention to optimise personal continuity for this group is highly warranted.

Methods
Following the UK Medical Research Council framework for complex Interventions, we will develop and evaluate an intervention to optimise personal continuity for older patients in general practice. In phase 0, we will perform a literature study to provide the theoretical basis for the intervention. In phase I we will define the components of the intervention by performing surveys and focus groups among patients, general practitioners, practice assistants and practice nurses, concluded by a Delphi study among members of our group. In phase II, we will test and finalise the intervention with input from a pilot study in two general practices. In phase III, we will perform a stepped wedge cluster randomised pragmatic trial. The primary outcome measure is continuity of care from the patients’ perspective, measured by the Nijmegen Continuity Questionnaire. Secondary outcome measures are level of implementation, barriers and facilitators for implementation, acceptability and feasibility of the intervention. In phase IV, we will establish the conditions for large-scale implementation.

Discussion
This is the first study to investigate an intervention for improving personal continuity for older patients in general practice. If proven effective, our intervention will enable General practitioners to improve the quality of care for their increasing population of older patients. The pragmatic design of the study will enable evaluation in real-life conditions, facilitating future implementation.

Trial registration number
Netherlands Trial Register, trial NL8132. Registered 2 November 2019.
Challenges and visions for managing pain-related insomnia in primary care using the hybrid CBT approach: a small-scale qualitative interview study with GPs, nurses, and practice managers
Authors: Collard V. E. J. , Moore C. , Nichols V. , Ellard D. R. , Patel S. , Sandhu H. , Parsons H. , Sharma U. , Underwood M. , Madan J. , Tang N. K. Y. 
Published: October 2021

Abstract
Background
Chronic pain and insomnia have a complex, bidirectional relationship – addressing sleep complaints alongside pain may be key to alleviating patient-reported distress and disability. Healthcare professionals have consistently reported wanting to offer psychologically informed chronic pain management at the primary care level. Research in secondary care has demonstrated good treatment efficacy of hybrid CBT for chronic pain and insomnia. However, primary care is typically the main point of treatment entry, hence may be better situated to offer treatments using a multidisciplinary approach. In this study, primary care service providers’ perception of feasibility for tackling pain-related insomnia in primary care was explored.

Methods
The data corpus originates from a feasibility trial exploring hybrid CBT for chronic pain and insomnia delivered in primary care. This formed three in-depth group interviews with primary care staff (n = 9) from different primary care centres from the same NHS locale. All interviews were conducted on-site using a semi-structured approach. Verbal data was recorded, transcribed verbatim and analysed using the thematic analysis process.

Results
Eight themes were identified – 1) Discrepant conceptualisations of the chronic pain-insomnia relationship and clinical application, 2) Mismatch between patients’ needs and available treatment offerings, 3) Awareness of psychological complexities, 4) Identified treatment gap for pain-related insomnia, 5) Lack of funding and existing infrastructure for new service development, 6) General shortage of psychological services for complex health conditions, 7) Multidisciplinary team provision with pain specialist input, and 8) Accessibility through primary care. These mapped onto four domains - Current understanding and practice, Perceived facilitators, Perceived barriers, Ideal scenarios for a new treatment service – which reflected the focus of our investigation. Taken together these provide key context for understanding challenges faced by health care professionals in considering and developing a new clinical service.

Conclusions
Primary care service providers from one locale advocate better, multidisciplinary treatment provision for chronic pain and insomnia. Findings suggest that situating this in primary care could be a feasible option, but this requires systemic support and specialist input as well as definitive trials for success.
Regorafenib combined with transarterial chemoembolization for unresectable hepatocellular carcinoma: a real-world study
Authors: Han Yue , Cao Guang , Sun Bin , Wang Jian , Yan Dong , Xu Haifeng , Shi Qinsheng , Liu Zechuan , Zhi Weihua , Xu Liang , Liu Bojun , Zou Yinghua 
Published: October 2021

Abstract
Background
The benefits and tolerability of transarterial chemoembolization (TACE) combined with regorafenib as a second-line therapy has not been reported for unresectable hepatocellular carcinoma (HCC). This study aimed to explore the benefits and tolerability of TACE combined with second-line regorafenib in patients with unresectable advanced HCC and failure to first-line treatment.

Methods
This was a multicenter retrospective study of patients with progression after first-line sorafenib and/or lenvatinib between 01/2019 and 04/2020 at four tertiary hospitals in China. The patients were treated with TACE. Then, 5–7 days after the first TACE, the patients started taking regorafenib for 3 weeks every 4-week cycle. The overall survival (OS), time to progression (TTP), progression-free survival (PFS), and adverse events (AEs) were observed.

Results
The median follow-up was 5.6 (range 0.7, 17.0) months. The median age was 60 (range 35, 79) years. There were 32 (84.2%) males. The patients underwent a median of three TACE sessions (range 1–13). The initial doses of regorafenib were 20 mg/d (n = 1, 2.6%), 80 mg/d (n = 10, 26.3%), 120 mg/d (n = 15, 39.5%), and 160 mg/d (n = 11, 28.9%). The incidence of grade 3/4 AEs was 15.8%. Two patients stopped regorafenib due to AEs. The median OS was 14.3 months. The median PFS and TTP were 9.1 (95% CI 4.0, 14.2) and 9.1 (95% CI 5.5, 12.8) months, respectively.

Conclusions
The present study provides real-world evidence indicating that regorafenib combined with TACE was beneficial and tolerable in patients with unresectable HCC. Additional prospective large-scale studies are required for confirmation.
Risk and characteristics of tuberculosis after anti-tumor necrosis factor therapy for inflammatory bowel disease: a hospital-based cohort study from Korea
Authors: Lee Jae Yong , Oh Kyunghwan , Hong Hee Seung , Kim Kyuwon , Hong Seung Wook , Park Jin Hwa , Hwang Sung Wook , Yang Dong-Hoon , Ye Byong Duk , Byeon Jeong-Sik , Myung Seung-Jae , Yang Suk-Kyun , Lee Ho-Su , Jo Kyung-Wook , Park Sang Hyoung 
Published: October 2021

Abstract
Background
Anti-tumor necrosis factor (TNF) treatment for inflammatory bowel disease (IBD) increases the risk of tuberculosis (TB) infection. In the present study, we analyzed the clinical characteristics and risks of TB in Korean patients with IBD who received anti-TNF treatment.

Methods
The study included patients with IBD who were treated using anti-TNF agents between January 2001 and June 2018 at the Asan Medical Center. Overall, 1434 patients with ulcerative colitis or Crohn’s disease were enrolled. We calculated the incidence of active TB infection after anti-TNF treatment and compared the clinical characteristics of the TB group with those of the non-TB group.

Results
Twenty-one patients (1.46%) developed active TB infection, and the incidence rate of active TB was 366.73 per 100,000 person-years. In total, 198 patients (14.9%) were positive for latent tuberculosis infection (LTBI), of whom only eight (4%) did not complete LTBI treatment. The age at which the anti-TNF therapy was started was significantly higher in the TB group than in the non-TB group (HR 1.041, 95% CI 1.014–1.069, p = 0.002), and as age increased, so did the incidence rate of active TB infection (linearity p < 0.001). There was no significant difference in the incidence rate of LTBI between the TB and non-TB groups (HR 0.896, 95% CI 0.262–3.066, p = 0.862).

Conclusions
In patients with IBD, the incidence rate of TB increased with age at anti-TNF therapy initiation. Active treatment of LTBI may lower the incidence of TB in patients with IBD who are to undergo anti-TNF therapy.
Plasma leakage in dengue: a systematic review of prospective observational studies
Authors: Rodrigo Chaturaka , Sigera Chathurani , Fernando Deepika , Rajapakse Senaka 
Published: October 2021

AbstractPlasma leakage is a precursor to life-threatening complications of dengue, but this group is poorly defined and not often reported in literature. Patients with Dengue haemorrhagic fever (DHF) as defined in the 1997 World Health Organization classification are often reported, and they all have plasma leakage, but some patients with plasma leakage do not meet the definition of DHF. The study aims to estimate the frequency of plasma leakage and DHF (as a surrogate of plasma leakage) in dengue and its variations based on virus serotype, geography, patient gender and pre-existing immunity to dengue. PUBMED, Scopus, EMBASE, CINAHL and Web of Science were searched for prospective observational studies reporting on plasma leakage or DHF. Quality of data was assessed using the NIH quality assessment tool for cohort studies. Forty-three studies that recruited 15,794 confirmed dengue patients were eligible. Cumulative frequency of plasma leakage was 36.8% (15 studies, 1642/4462, 95% CI 35.4–38.2%), but surprisingly the estimated cumulative frequency of DHF was higher (45.7%, 32 studies, 4758/10417, 95% CI 44.7–46.6%), indicating that current medical literature over-reports DHF or under-reports plasma leakage. Therefore, a reliable estimate for the proportion of dengue patients developing plasma leakage cannot be derived from existing medical literature even after applying rigorous inclusion criteria to select homogenous studies. Plasma leakage is an important marker of “at-risk” dengue patients and standardizing its definition, diagnosis and reporting should be a priority in research and global policy.
A de novo variant of POLR3B causes demyelinating Charcot-Marie-Tooth disease in a Chinese patient: a case report
Authors: Xue Yan-Yan , Cheng Hao-Ling , Dong Hai-Lin , Yin Hou-Min , Yuan Yun , Meng Ling-Chao , Wu Zhi-Ying , Yu Hao 
Published: October 2021

Abstract
Background
Charcot-Marie-Tooth (CMT) disease is a group of inherited peripheral neuropathies, which are subdivided into demyelinating and axonal forms. Biallelic mutations in POLR3B are the well-established cause of hypomyelinating leukodystrophy, which is characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism. To date, only one study has reported the demyelinating peripheral neuropathy phenotype caused by heterozygous POLR3B variants.

Case presentation
A 19-year-old male patient was referred to our hospital for progressive muscle weakness of the lower extremities. Physical examination showed muscle atrophy, sensory loss and deformities of the extremities. Nerve conduction studies and electromyography tests revealed sensorimotor demyelinating polyneuropathy with secondary axonal loss. Trio whole-exome sequencing revealed a de novo variant in POLR3B (c.3137G > A).

Conclusions
In this study, we report the case of a Chinese patient with a de novo variant in POLR3B (c.3137G > A), who manifested demyelinating CMT phenotype without additional neurological or extra-neurological involvement. This work is the second report on POLR3B-related CMT.
Effects of dezocine on morphine tolerance and opioid receptor expression in a rat model of bone cancer pain
Authors: Wu Lin-xin , Dong Yan-peng , Zhu Qian-mei , Zhang Bo , Ai Bo-lun , Yan Tao , Zhang Guo-hua , Sun Li 
Published: October 2021

AbstractBackgroundClinically, the coadministration of opioids to enhance antinociception and decrease tolerance has attracted increasing research attention. We investigated the effects of dezocine, a mu- and kappa-opioid receptor agonist/antagonist, on morphine tolerance and explored the involvement of opioid receptor expression in a rat model of bone cancer pain.MethodsThermal nociceptive thresholds were measured after the subcutaneous injection of morphine (10 mg/kg) alone or combined with dezocine (10 or 1 mg/kg) for 7 consecutive days. Real-time PCR and western blot analysis were used to examine opioid receptor expression in the periaqueductal gray (PAG) and spinal cord.ResultsThe analgesic effect was significantly decreased after 4 days of morphine administration. We observed that low-dose dezocine significantly attenuated morphine tolerance without reducing the analgesic effect of morphine. Low-dose dezocine coadministration significantly reversed the downregulated expression of mu (MOR) and delta (DOR) opioid receptors in the PAG and the upregulated expression of kappa (KOR) and DOR in the spinal cord induced by morphine. Moreover, low-dose dezocine coadministered with morphine significantly inhibited KOR expression in both the PAG and spinal cord.ConclusionsThe combination of low-dose dezocine with morphine may prevent or delay the development of morphine tolerance in a rat model of bone cancer pain. The regulation of opioid receptor expression in the PAG and spinal cord may be part of the mechanism.