bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glioma progression and recurrence involving maintenance and expansion strategies of glioma stem cells by organizing self-advantageous niche microenvironments
Authors: Taga Tetsuya , Tabu Kouichi 
Published: September 2020

AbstractDue to the nature of enhanced resistance to conventional chemo/radiotherapies and metastasis, highly tumorigenic cancer stem cells (CSCs) have been proposed as a promising target for cancer eradication. To tackle the therapeutic difficulties of cancers involving CSCs, extensive research efforts have been directed toward understanding the extracellular microenvironments of CSCs, i.e., CSC niche, which plays important roles in CSC maintenance and expansion. Here we review recently identified mechanisms of maintenance and expansion of glioma CSCs (GSCs) leading to glioma progression and recurrence, with particular emphasis on the reports made by studies with a unique approach using polymer microarrays screening and with a unique viewpoint of necrotic particles. The polymer-based approach identified two groups of niche components, extracellular matrices (ECMs) and iron, and uncovered that co-expression of ECM-, iron-, and macrophage-related genes is predictive of glioma patients’ outcome. The study in view of a unique fraction of GSC-derived necrotic particles proposed that such particles develop GSC-supportive tumor-associated macrophages (TAMs). Taken together, these studies provide new insights into the mechanisms underlying GSC-driven niche development, i.e., organization of the self-advantageous niche microenvironments for GSC maintenance and expansion leading to glioma progression and recurrence. A series of such studies can redefine the current concept of anti-GSC niche therapy that targets ligands/receptors supporting GSCs, and have potential to accelerate cancer therapy development.
Granulomatous inflammation in pulmonary pathology of 2019 novel coronavirus pneumonia: case report with a literature review
Authors: Usturalı Keskin Elif , Tastekin Ebru , Can Nuray , Usta İnci , Tuncbilek Nermin , Karabulut Derya , Kula Osman , Kırkızlar Onur 
Published: September 2020

Abstract
Background
Coronavirus disease 2019 (COVID-19), which started in Wuhan, China, in late December 2019, was declared a pandemic, infecting more than twelve million people worldwide. Few studies have reported the findings of lung biopsies in COVID-19. Here, granulomatous inflammation was reported for the first time in COVID-19 lung biopsy.

Case presentation
A 54-year-old woman presented to a primary care facility with fever, dry cough, and fatigue. Antibiotherapy was administered for 10 days with the diagnosis of upper respiratory tract infection. However, her condition did not improve and she was admitted to the hospital. In physical examination, crepitant rales were heard in both lungs. Anemia and thrombocytopenia were detected in laboratory tests and she was referred to the hematology clinic. Bone marrow aspiration and flow cytometry showed she had acute myeloid leukemia. Computed tomography-integrated positron emission tomography with a history of previous breast cancer revealed a heterogeneous mass-like lesion in the left lung. The primary malignancy could not be ruled out and tru-cut biopsy was performed. Tests for tuberculosis were negative. Throat swab sample was taken and a real-time polymerase chain reaction confirmed that she had COVID-19. Radiological findings were evaluated as the progression of COVID-19 pneumonia on computed tomography 6 days after biopsy. Alveolar damage, edema, vascular congestion, mild inflammatory infiltration, type-2 pneumocyte hyperplasia, interstitial fibrosis, early fibrotic changes, fibrinous, organized pneumonia pattern, noncaseating granulomatous inflammation, and desquamation in alveolar epithelial cells were noted in lung biopsy.

Conclusions
There were only a few case reports that described lung biopsy findings in COVID-19 at the time of manuscript preparation. This was the first case of noncaseating granulomatous inflammation described in a COVID-19 case.
Comparative study between double inversion recovery (DIR) and fluid-attenuated inversion recovery (FLAIR) MRI sequences for detection of cerebral lesions in multiple sclerosis
Authors: Elkholy Shaima Fattouh , Sabet Marianne Abdallah , Mohammad Mohammad Edrees , Asaad Ramy Edward Ibrahim 
Published: September 2020

Abstract
Background
Multiple sclerosis (MS) is a common chronic inflammatory demyelinating disorder more common in young adults. MS is characterized mainly with white matter (WM) affection; however, considerable gray matter (GM) involvement is also noted in many patients. MRI is used for diagnosis and follow up of the disease using different pulse sequences; FLAIR imaging provides the highest sensitivity in the detection of supratentorial, juxtacortical, and the periventricular lesions but is less sensitive in the posterior fossa. A double inversion recovery (DIR) pulse sequence was recently introduced to improve the visibility of GM lesions and especially cortical lesions. The aim of this study is to assess the role of DIR sequence in the detection of brain lesions in patients with MS compared to FLAIR sequence.

Results
DIR showed a significantly higher number of MS lesions in infratentorial region (2.9 ± 0.4 compared to 2.25 ± 0.3 in FLAIR) with a statistically significant difference (p = 0.002) and also in supratentorial periventricular regions (11.84 ± 8.07 in DIR and 11.31 ± 8.07 in FLAIR, p < 0.001). DIR imaging also demonstrated significantly more intracortical lesions (7.12 ± 1.2 compared to 1.4 ± 0.9 in FLAIR imaging) with a statistically significant difference (p < 0.001). On the other hand, corpus callosum lesions were significantly higher on FLAIR (0.84 ± 0.1) with respect to DIR imaging (0.68 ± 0.1) with a statistically significant difference in between (p = 0.025).

Conclusion
DIR is a powerful conventional MRI sequence for visualization of brain lesions in patients with MS and is superior to FLAIR sequence in detecting lesions in different locations, namely cortical, periventricular, and infratentorial regions; hence, DIR can be added to the MRI protocol of MS patients or even can replace FLAIR which would be of a good diagnostic value with only 80 s added to the scan time.
The pattern of allopurinol prescription in a university hospital practice
Authors: Saad Sahar Ahmed , Sabkar Maha Mahmoud 
Published: September 2020

Abstract
Background
Allopurinol as a drug is commonly used to treat gout and its complications. The aim usually is to lower the level of serum uric acid. Also, it was found to be prescribed in cases of asymptomatic hyperuricemia. However, this medication has serious side effects and some of these are fatal. So the aim of the current research work is to look at its use, whether properly indicated or not, in a university hospital.

Results
A total of 427 patients were included in this study. Only 3.7% (16) of the patients had the drug for significant hyperuricemia. Gout was confirmed in 40 (9.4%) patients.

Conclusion
It is clear that most patients received allopurinol without proper indications. The inappropriate use of allopurinol should be looked at to reduce the cost of medication and more importantly to avoid possible adverse effects.
Co-occurring mental disorder and substance use disorder in young people: aetiology, assessment and treatment
Authors: Otasowie John 
Published: September 2020

SUMMARYDual diagnosis is one of several terms used to identify individuals diagnosed with a co-occurring mental disorder and substance use disorder. The existence of a dual diagnosis in adolescents is often associated with functional impairment in various life domains, causing physical health problems, relational conflicts, educational/vocational underachievement and legal problems. Dual diagnosis is difficult to treat and can result in tremendous economic burden on healthcare, education and justice systems. It is essential for clinicians caring for young people to be knowledgeable about dual diagnosis to ensure that it is identified early and treated. This article aims to provide an overview of dual diagnosis, increase its awareness and promote a realistic treatment approach.
Long-Term Follow-Up of Ibrutinib Monotherapy in Symptomatic, Previously Treated Patients With Waldenström Macroglobulinemia
Authors: Treon Steven P. , Meid Kirsten , Gustine Joshua , Yang Guang , Xu Lian , Liu Xia , Patterson Christopher J. , Hunter Zachary R. , Branagan Andrew R. , Laubach Jacob P. , Ghobrial Irene M. , Palomba M. Lia , Advani Ranjana , Castillo Jorge J. 
Published: September 2020

PURPOSE We report the long-term findings and final analysis of a pivotal multicenter trial of ibrutinib monotherapy in previously treated patients with Waldenström macroglobulinemia (WM). PATIENTS AND METHODS Sixty-three symptomatic patients with median prior therapies of two (range, one to nine therapies), of whom 40% were refractory to their previous therapy, received ibrutinib at 420 mg/d. Dose reduction was permitted for toxicity. RESULTS The median follow-up was 59 months, and overall and major response rates were 90.5% and 79.4%, respectively. At best response, median serum immunoglobulin M declined from 3,520 to 821 mg/dL, bone marrow disease involvement declined from 60% to 20%, and hemoglobin rose from 10.3 to 14.2 g/dL ( P < .001 for all comparisons). Responses were impacted by mutated (Mut) MYD88 and CXCR4 status. Patients with MYD88Mut, wild-type (WT) CXCR4 showed higher major (97.2% v 68.2%; P < .0001) and very good partial (47.2% v 9.1%; P < .01) response rates and a shorter time to major response (1.8 v 4.7 months; P = .02) versus patients with MYD88Mut CXCR4Mut. Conversely, four patients who had MYD88WT disease showed no major responses. The median 5-year progression-free survival (PFS) rate for all patients was not reached, and was 70% and 38% for those with MYD88Mut CXCR4WT and MYD88Mut CXCR4Mut WM, respectively ( P = .02). In patients with MYD88WT, the median PFS was 0.4 years ( P < .01 for three-way comparisons). The 5-year overall survival rate for all patients was 87%. Grade ≥ 3 adverse events in more than one patient at least possibly related included neutropenia (15.9%), thrombocytopenia (11.1%), and pneumonia (3.2%). Eight patients (12.7%) experienced atrial arrhythmia, and seven of the eight continued therapy with medical management. CONCLUSION Ibrutinib is highly active and produces long-term disease control in previously treated patients with WM. Treatment is tolerable. Response depth, time to major response, and PFS are impacted by MYD88 and CXCR4 mutation status.
Predictors of the Response to Dopaminergic Therapy in Patients With Prolactinoma
Authors: Hage Camille , Salvatori Roberto 
Published: September 2020

Abstract

Purpose
Withdrawal of dopamine agonist (DA) therapy in patients with prolactinoma who are controlled by a small dose of medication is recommended by several guidelines. So far, the likelihood of reaching withdrawal conditions based on baseline characteristics remains uncertain.

Methods
We retrospectively examined early clinical, radiological, or biochemical features that may predict the likelihood of reaching withdrawal conditions in prolactinoma patients. Data were obtained in a single academic medical center in the United States from patients seen between 2000 and 2018. Using multiple logistic regression, we compared patients who reached withdrawal conditions with those who did not.

Results
Of 213 patients, 78 (36.6%) reached withdrawal conditions after at least 2 years of DA treatment. Initial maximal tumor diameter was significantly smaller in those who reached withdrawal conditions than in those who did not. Percent prolactin change at the first check from initiation of DA therapy and parasellar invasiveness were predictors of reaching withdrawal conditions. With constant independent variables, there was a 7% increase in odds for reaching withdrawal conditions for every 1% decrease in percent prolactin change at first check after DA therapy start (P = 0.0000). Parasellar invasion decreased the odds of reaching withdrawal conditions by 84% (P = 0.0000).

Conclusions
DA remains a potential life-long treatment modality for most prolactinoma patients. Patients with parasellar invasiveness and low prolactin percent change from baseline to first prolactin check are more likely to require long-term treatment.
Comprehensive Risk Assessment of Morbidity in Pediatric Patients Undergoing Noncardiac Surgery: An Institutional Experience
Authors: Nasr Viviane G. , Valencia Eleonore , Staffa Steven J. , Faraoni David , DiNardo James A. , Berry Jay G. , Leahy Izabela , Ferrari Lynne 
Published: September 2020

BACKGROUND:
Utilizing the intrinsic surgical risk (ISR) and the patient’s chronic and acute conditions, this study aims to develop and validate a comprehensive predictive model of perioperative morbidity in children undergoing noncardiac surgery.

METHODS:
Following institutional review board (IRB) approval at a tertiary care children’s hospital, data for all noncardiac surgical encounters for a derivation dataset from July 2017 to December 2018 including 16,724 cases and for a validation dataset from January 2019 to December 2019 including 9043 cases were collected retrospectively. The primary outcome was a composite morbidity score defined by unplanned transfer to an intensive care unit (ICU), acute respiratory failure requiring intubation, postoperative need for noninvasive or invasive positive pressure ventilation, or cardiac arrest. Internal model validation was performed using 1000 bootstrap resamples, and external validation was performed using the 2019 validation cohort.

RESULTS:
A total of 1519 surgical cases (9.1%) experienced the defined composite morbidity. Using multivariable logistic regression, the Risk Assessment of Morbidity in Pediatric Surgery (RAMPS) score was developed with very good predictive ability in the derivation cohort (area under the curve [AUC] = 0.805; 95% confidence interval [CI], 0.795–0.816), very good internal validity using 1000 bootstrap resamples (bias-corrected Nagelkerke R
2 = 0.21 and Brier score = 0.07), and good external validity (AUC = 0.783; 95% CI, 0.770–0.797). The included variables are age <5 years, critically ill, chronic condition indicator (CCI) ≥3, significant CCI ≥2, and ISR quartile ≥3. The RAMPS score ranges from 0 to 10, with the risk of composite morbidity ranging from 1.8% to 42.7%.

CONCLUSIONS:
The RAMPS score provides the ability to identify a high-risk cohort of pediatric patients using a 5-component tool, and it demonstrated good internal and external validity and generalizability. It also provides an opportunity to improve perioperative planning with the intent of improving both individual-patient outcomes and the appropriate allocation of health care resources.
New insights into non-transcriptional regulation of mammalian core clock proteins
Authors: Crosby Priya , Partch Carrie L. 
Published: September 2020

ABSTRACT
Mammalian circadian rhythms drive ∼24 h periodicity in a wide range of cellular processes, temporally coordinating physiology and behaviour within an organism, and synchronising this with the external day–night cycle. The canonical model for this timekeeping consists of a delayed negative-feedback loop, containing transcriptional activator complex CLOCK–BMAL1 (BMAL1 is also known as ARNTL) and repressors period 1, 2 and 3 (PER1, PER2 and PER3) and cryptochrome 1 and 2 (CRY1 and CRY2), along with a number of accessory factors. Although the broad strokes of this system are defined, the exact molecular mechanisms by which these proteins generate a self-sustained rhythm with such periodicity and fidelity remains a topic of much research. Recent studies have identified prominent roles for a number of crucial post-transcriptional, translational and, particularly, post-translational events within the mammalian circadian oscillator, providing an increasingly complex understanding of the activities and interactions of the core clock proteins. In this Review, we highlight such contemporary work on non-transcriptional events and set it within our current understanding of cellular circadian timekeeping.
APC/CCdh1 is required for the termination of chromosomal passenger complex activity upon mitotic exit
Authors: Tsunematsu Takaaki , Arakaki Rieko , Kawai Hidehiko , Ruppert Jan , Tsuneyama Koichi , Ishimaru Naozumi , Earnshaw William C. , Pagano Michele , Kudo Yasusei 
Published: September 2020

ABSTRACT
During mitosis, the chromosomal passenger complex (CPC) ensures the faithful transmission of the genome. The CPC is composed of the enzymatic component Aurora B (AURKB) and the three regulatory and targeting components borealin, INCENP, and survivin (also known as BIRC5). Although the CPC is known to be involved in diverse mitotic events, it is still unclear how CPC function terminates after mitosis. Here we show that borealin is ubiquitylated by the anaphase promoting complex/cyclosome (APC/C) and its cofactor Cdh1 (also known as FZR1) and is subsequently degraded in G1 phase. Cdh1 binds to regions within the N terminus of borealin that act as a non-canonical degron. Aurora B has also been shown previously to be degraded by the APC/CCdh1 from late mitosis to G1. Indeed, Cdh1 depletion sustains an Aurora B activity with stable levels of borealin and Aurora B throughout the cell cycle, and causes reduced efficiency of DNA replication after release from serum starvation. Notably, inhibition of Aurora B kinase activity improves the efficiency of DNA replication in Cdh1-depleted cells. We thus propose that APC/CCdh1 terminates CPC activity upon mitotic exit and thereby contributes to proper control of DNA replication.
Vascular endothelial function is improved after active mattress use
Authors: Baker Gary , Bloxham Saul , Laden Joe , Gush Rodney 
Published: September 2020

Objective: Active mattresses are used to prevent, treat and relieve pressure ulcers (PU) by intermittent contact pressure/relief. However, no studies have directly assessed the vascular endothelial response to long-term active mattress use. This study investigated the hypothesis that eight weeks use of an active mattress would lead to improvements in vascular endothelial function in healthy participants. Methods: Physiological parameters of baseline skin temperature (BskT), resting blood flow (RBF) and endothelial function as measured using post-occlusive reactive hyperaemia (PORH), were assessed at baseline (week 0); following eight weeks of sleeping on an active mattress, and after an eight week washout period (at week 16). Results: We recruited 10 healthy participants (four male, age 52.7±8.5 years, six female age 51.8±17.5 years). Following active mattress use RBF, PORH and BskT at the hallux pulp increased by 336%, 197% and 3.5°C, respectively. Mean values increased from 24.3±38.3 perfusion units to 106.0±100.3 perfusion units (p=0.021) and from 13,456±10,225 to 40,252±23,995 perfusion units x seconds (p=0.003) and from 22.9±2.5°C to 26.4±1.9°C (p<0.001), respectively. Conclusion: Active mattress use for eight weeks leads to significant improvements in RBF, PORH, and BskT. These results suggest that active mattress use can improve endothelial function. Future research is required to explore the potential of active mattress use in the treatment and management of diseases and conditions that would benefit from an improved endothelial function.
Pressure ulcer prevention using an alternating-pressure mattress overlay: the MATCARP project
Authors: Meaume Sylvie , Marty Marc 
Published: September 2020

Objective: The primary objective was to assess the incidence of pressure ulcer (PU) in patients at high risk of PU and lying between 15–20 hours per day on an alternating-pressure mattress overlay (APMO). Secondary objectives were the patient's satisfaction with the comfort of the APMO, patient acceptance of its sound level, and the care team's assessment of its use and the moisture level. Method: This prospective observational study was conducted in three rehabilitation centres and two nursing homes between June 2016 and March 2017. To be included, patients should not have PU at baseline and present a high risk of PU (Braden score between 10–15). The primary endpoint was the percentage of patients in whom a PU developed over a 35-day period. Results: A total of 83 patients were included in the study. Neurological disease was responsible for the reduced mobility of 44 (53.7%) patients, 10 patients (12.0%) dropped out (one patient for a serious adverse event (femoral neck fracture) considered not to be related to the APMO, four patients for adverse events, two of which were considered to be related to APMO and five for other reasons, including, in one case, discomfort with the APMO. These patients were considered in the analysis. Over the study period, 1.2% (1/83) (95% confidence interval (CI): 0.03 to 6.53) of patients developed a PU. Patient satisfaction with the comfort of the APMO, patient acceptance of its sound level, and the care team's assessment of its use were considered satisfying for most patients. Conclusion: Based on the findings of this study of a low incidence of PU in participating patients, the use of an AMPO is recommended in high-risk patients lying for between 15–20 hours a day.
Photonic compressive sensing of sparse radio frequency signals with a single dual-electrode Mach–Zehnder modulator
Authors: Yang Bo , Yang Shuna , Cao Zizheng , Ou Jun , Zhai Yanrong , Chi Hao 
Published: September 2020

A novel approach to realizing compressive sensing (CS) of sparse radio frequency (RF) signals based on photonic random demodulation (RD) is proposed. The key function of mixing the RF signal under test and the bipolar pseudo-random binary sequence (PRBS) in photonic RD is implemented with a single dual-electrode Mach–Zehnder modulator (DEMZM). By properly setting the DC bias of the DEMZM at

V
π

and the voltages of the PRBS at

±

V
π

/

2

, a pure desired multiplication term between the signal and the bipolar PRBS is obtained after an AC-coupled photodetector (PD), which not only simplifies the modeling of the CS link but also improves the recovery performance. A proof-of-concept experiment is demonstrated where a sparse signal with spectral components of 500 MHz and 950 MHz is successfully identified with a compression ratio of 20. Simulation results are also given to show the advantage of the given photonic CS scheme with bipolar random mixing.
Analyzing ingrowth using zero-inflated negative binomial models
Authors: Lappi Juha , Pukkala Timo 
Published: September 2020

Ingrowth is an important element of stand dynamics in several silvicultural systems, especially in continuous cover forestry. Earlier predictive models for ingrowth in Finnish forests are few and not based on up-to-date statistical methods. Ingrowth is here defined as the number of trees over 1.3 m entering a plot. This study developed new ingrowth models for Scots pine ( L.), (Picea abies (L.) H. Karst.) and birch ( Roth and Ehrh.) using data from the permanent sample plots of the Finnish national forest inventory. The data were over-dispersed compared to a Poisson process and had many zeros. Therefore, a zero-inflated negative binomial model was used. The total and species-specific stand basal areas, temperature sum and fertility class were used as predictors in the ingrowth models. Both fixed-effects and mixed-effects models were fitted. The mixed-effects model versions included random plot effects. The mixed-effects models had larger likelihoods but provided biased predictions. Also censored prediction was considered where only a certain maximum number of ingrowth trees were accepted for a plot. The models predicted most pine ingrowth in pine-dominated stands on sub-xeric and xeric sites where stand basal area was low. The predicted amount of spruce ingrowth was maximized when the basal area of spruce was 13 m ha. Increasing temperature sum increased spruce ingrowth. Predicted birch ingrowth decreased with increasing stand basal area and towards low fertility classes. An admixture of pine increased the predicted amount of spruce ingrowth.Pinus sylvestrisNorway spruceBetula pendulaB. pubescens2â1