bluuebunny/crossref_metadata_2025 huggingface dataset:
Management, Medication Use and Economic Burden of Asthma among Hajj and Umrah Pilgrims
Authors: Haseeb Abdul , Alzahrani Arwa Saleh , Bifari Nisrin Nasseraldeen , Bugis Samah Mohammed , Alharbi Shaza Eid O. , Ridnah Dina Jameel , Kutob Weam Waiel , Alzhrani Eman Abdullah , Al-Nass Ghadair , Fadaq Mohamed , Al-Sulaimani Turki Mohammad Noor , Iqbal Muhammad Shahid
Published: April 2020

Introduction: During Hajj and Umrah season, asthma-related acute admissions produce the enormous burden on healthcare facilities and causes delay in admissions for more severe cases, e.g. myocardial infarction, cardiac failure and severe trauma cases. Therefore, the snapshot of asthma-related admissions during the Hajj and Umrah season was determined by asthma-related admissions and medication use and economic burden during Hajj and Umrah pilgrimage season.

Methodology: All asthma-related admissions during the month of Ramadan (fasting month) and Hajj pilgrimage were assessed from patients’ data retrospectively. The convenience sampling strategy was used to retrieve study variables. Statistical Package for Social Science (SPSS) Version 22.0 was used to analyze the data.

Results: A total of 271 patients were selected as per inclusion criteria, the majority of them were males 153 (56.5%), while most of them were Saudi 70 (35.8%) and Egyptians 86 (31.7%). During hospitalization, the common treatment for acute exacerbations was inhaled corticosteroids 224 (86.3%), IV corticosteroids 129 (47.6%), Inhaled short-acting beta-agonists 244 (90%) and inhaled bronchodilators (ipratropium bromide) 237(87.5 5%).

Conclusion: This periodic mapping of asthma-related admissions and its management during these massive gathering events is indeed a significant effort to explore issues of acute asthma exacerbations management and to provide information to plan for future interventions and policies.
The Adverse Effects Reporting of Antibiotic Induced Diarrhea
Authors: Ahmed Nehad J.
Published: April 2020

Introduction: In Saudi Food and Drug Authority, there is a center called National Pharmacovigilance and Drug Safety Center responsible for adverse events reporting. This study aims to demonstrate the antibiotic induced diarrhea reporting by National Pharmacovigilance and Drug Safety Center in Saudi Arabia.

Methodology: This is a retrospective study about the reporting of diarrhea adverse effects caused by antibiotics. The data were collected from the adverse effects reports that were submitted to Saudi Food and Drug Authority in 2017 and 2018.

Results: Gastrointestinal adverse effects reports were mainly for penicillin antibiotics. The major gastrointestinal adverse effect of penicillin was diarrhea (100 reports out of 147 reports for penicillin include diarrhea). Most of the diarrhea reports were caused by Amoxicillin/Clavulanate followed by Amoxicillin.

Conclusion: One of the major adverse effects for antibiotics is diarrhea that is mainly occurred by penicillin antibiotics. The majority of cases of antibiotics-associated diarrhea are not serious, but still affect the patients’ quality of life. Therefore, it is important to increase the awareness regarding medications adverse effects and their reporting.
Retroperitoneal Liposarcoma: Treatment Outcome in Primary and Secondary Surgical Intervention
Authors: Ladurner Ruth , Strohäker Jens , Birkert Christian , Kopp Hans-Georg , Königsrainer Alfred , Bachmann Robert
Published: April 2020

Background

Approximately 30% to 40% of all retroperitoneal soft tissue tumors are sarcomas, with liposarcoma prevailing in approximately 50% of these cases. Retroperitoneal liposarcomas typically show a high rate of local recurrence and late distant metastases. The aim of our retrospective analysis was to investigate the efficacy of treatment in our patients with liposarcoma.

Methods

Thirty-four consecutive patients underwent surgery in our clinic between October 2004 and November 2017. Liposarcomas arising from the mesenteric or abdominal adipose tissue or the pelvis were excluded.

Results

Of 34 patients, 23 (67.6%) presented with primary and 11 (32.4%) with recurrent disease. In 7 of the 34 patients (20.6%), a radical resection (R0) could be achieved, and in 27 patients (76.5%) resection was marginal (R1). Time to recurrence was not affected by neoadjuvant radiotherapy. Patients who underwent systemic chemotherapy followed by radiotherapy developed earlier recurrences (P = 0.003) than patients with neoadjuvant radiotherapy only. Overall survival was significantly better in the neoadjuvant group (P 0.045)

Conclusions

Combining surgical resection with neoadjuvant radiation treatment showed survival benefits in primary but not recurrent disease. Repeated surgery remains a valid approach in carefully selected patients, but all patients should be referred to a center of expertise in multimodal treatment approaches for retroperitoneal liposarcomas.
Regulating the regulators: role of phosphorylation in modulating the function of the GBF1/BIG family of Sec7 ARF‐GEFs
Authors: Walton Kendall , Leier Andre , Sztul Elizabeth
Published: April 2020

Membrane traffic between secretory and endosomal compartments is vesicle‐mediated and must be tightly balanced to maintain a physiological compartment size. Vesicle formation is initiated by guanine nucleotide exchange factors (GEFs) that activate the ARF family of small GTPases. Regulatory mechanisms, including reversible phosphorylation, allow ARF‐GEFs to support vesicle formation only at the right time and place in response to cellular needs. Here, we review current knowledge of how the Golgi‐specific brefeldin A‐resistance factor 1 (GBF1)/brefeldin A‐inhibited guanine nucleotide exchange protein (BIG) family of ARF‐GEFs is influenced by phosphorylation and use predictive paradigms to propose new regulatory paradigms. We describe a conserved cluster of phosphorylation sites within the N‐terminal domains of the GBF1/BIG ARF‐GEFs and suggest that these sites may respond to homeostatic signals related to cell growth and division. In the C‐terminal region, GBF1 shows phosphorylation sites clustered differently as compared with the similar configuration found in both BIG1 and BIG2. Despite this similarity, BIG1 and BIG2 phosphorylation patterns are divergent in other domains. The different clustering of phosphorylation sites suggests that the nonconserved sites may represent distinct regulatory nodes and specify the function of GBF1, BIG1, and BIG2.
Darolutamide antagonizes androgen signaling by blocking enhancer and super‐enhancer activation
Authors: Baumgart Simon J. , Nevedomskaya Ekaterina , Lesche Ralf , Newman Richard , Mumberg Dominik , Haendler Bernard
Published: April 2020

Prostate cancer (PCa) is one of the most frequent tumor types in the male Western population. Early‐stage PCa and late‐stage PCa are dependent on androgen signaling, and inhibitors of the androgen receptor (AR) axis represent the standard therapy. Here, we studied in detail the global impact of darolutamide, a newly approved AR antagonist, on the transcriptome and AR‐bound cistrome in two PCa cell models. Darolutamide strongly depleted the AR from gene regulatory regions and abolished AR‐driven transcriptional signaling. Enhancer activation was blocked at the chromatin level as evaluated by H3K27 acetylation (H3K27ac), H3K4 monomethylation (H3K4me1), and FOXA1, MED1, and BRD4 binding. We identified genomic regions with high affinities for the AR in androgen‐stimulated, but also in androgen‐depleted conditions. A similar AR affinity pattern was observed in healthy and PCa tissue samples. High FOXA1, BRD4, H3K27ac, and H3K4me1 levels were found to mark regions showing AR binding in the hormone‐depleted setting. Conversely, low FOXA1, BRD4, and H3K27ac levels were observed at regulatory sites that responded strongly to androgen stimulation, and AR interactions at these sites were blocked by darolutamide. Beside marked loss of AR occupancy, FOXA1 recruitment to chromatin was also clearly reduced after darolutamide treatment. We furthermore identified numerous androgen‐regulated super‐enhancers (SEs) that were associated with hallmark androgen and cell proliferation‐associated gene sets. Importantly, these SEs are also active in PCa tissues and sensitive to darolutamide treatment in our models. Our findings demonstrate that darolutamide is a potent AR antagonist blocking genome‐wide AR enhancer and SE activation, and downstream transcription. We also show the existence of a dynamic AR cistrome that depends on the androgen levels and on high AR affinity regions present in PCa cell lines and also in tissue samples.
Extended in vitro culture of primary human mesenchymal stem cells downregulates Brca1‐related genes and impairs DNA double‐strand break recognition
Authors: Bao Xuanwen , Wang Jing , Zhou Guangming , Aszodi Attila , Schönitzer Veronika , Scherthan Harry , Atkinson Michael J. , Rosemann Michael
Published: April 2020

Mesenchymal stem cells (MSCs) are multilineage adult stem cells with considerable potential for cell‐based regenerative therapies. In vitro expansion changes their epigenetic and cellular properties, with a poorly understood impact on DNA damage response (DDR) and genome stability. We report here results of a transcriptome‐based pathway analysis of in vitro‐expanded human bone marrow‐derived mesenchymal stem cell (hBM‐MSCs), supplemented with cellular assays focusing on DNA double‐strand break (DSB) repair. Gene pathways affected by in vitro aging were mapped using gene ontology, KEGG, and GSEA, and were found to involve DNA repair, homologous recombination (HR), cell cycle control, and chromosomal replication. Assays for the recognition (γ‐H2AX + 53BP1 foci) and repair (pBRCA1 + γ‐H2AX foci) of X‐ray‐induced DNA DSBs in hBM‐MSCs show that over a period of 8 weeks of in vitro aging (i.e., about 10 doubling times), cells exhibit a reduced DDR and a higher fraction of residual DNA damage. Furthermore, a distinct subpopulation of cells with impaired DNA DSB recognition was observed. Several genes that participate in DNA repair by HR (e.g., Rad51, Rad54, BRCA1) show a 2.3‐ to fourfold reduction of their mRNA expression by qRT‐PCR. We conclude that the in vitro expansion of hMSCs can lead to aging‐related impairment of the recognition and repair of DNA breaks.
A practical cyberattack contingency plan for radiation oncology
Authors: Zhang Baoshe , Chen Shifeng , Nichols Elizabeth , D’Souza Warren , Prado Karl , Yi Byongyong
Published: April 2020

Purpose

This article presents a solution for continuing radiation therapy without interruption in the event of a cyberattack to the radiation oncology information systems (ROIS). This process could be easily deployed to any radiation oncology practice, with little clinical overhead or burden.

Methods and Materials

The solution automatically retrieves all essential information from the clinical ROIS for each under‐treatment patient and periodically (e.g., daily) saves these data to a dedicated secure server for recovery. In the event that the clinical ROIS is not functioning as a result of a cyberattack, this essential information is used to build a new secondary ROIS server to continue radiotherapy treatments until the main ROIS is recovered. Once the cyberattack threat is cleared, the clinical ROIS server is rebuilt from the institution’s enterprise backup. The newly accumulated treatment information for each patient is then exported from the secondary ROIS to bring the clinical ROIS up to date.

Results

The Department of Radiation Oncology at the University of Maryland Medical System implemented this solution for clinical use with the Varian ARIA ROIS in the management of ~250 daily radiotherapy treatments, inclusive of a proton center. This solution was determined to be a feasible and affordable business continuity plan for the radiation oncology practice by minimizing radiation treatment downtime to a couple of hours in a simulated cyberattack drill.

Conclusions

The proposed solution can achieve continuation of radiation therapy treatment without treatment breaks in the event of a cyberattack. It also provides cushion time for radiation oncology departments to rebuild their clinical ROIS systems from the enterprise data backup.
Heritability of alpha and sensorimotor network changes in temporal lobe epilepsy
Authors: Yaakub Siti N. , Tangwiriyasakul Chayanin , Abela Eugenio , Koutroumanidis Michalis , Elwes Robert D. C. , Barker Gareth J. , Richardson Mark P.
Published: April 2020

Objective

Electroencephalography (EEG) features in the alpha band have been shown to differ between people with epilepsy and healthy controls. Here, in a group of patients with mesial temporal lobe epilepsy (mTLE), we seek to confirm these EEG features, and using simultaneous functional magnetic resonance imaging, we investigate whether brain networks related to the alpha rhythm differ between patients and healthy controls. Additionally, we investigate whether alpha abnormalities are found as an inherited endophenotype in asymptomatic relatives.

Methods

We acquired scalp EEG and simultaneous EEG and functional magnetic resonance imaging in 24 unrelated patients with unilateral mTLE, 23 asymptomatic first‐degree relatives of patients with mTLE, and 32 healthy controls. We compared peak alpha power and frequency from electroencephalographic data in patients and relatives to healthy controls. We identified brain networks associated with alpha oscillations and compared these networks in patients and relatives to healthy controls.

Results

Patients had significantly reduced peak alpha frequency (PAF) across all parietal and occipital electrodes. Asymptomatic relatives also had significantly reduced PAF over 14 of 17 parietal and occipital electrodes. Both patients and asymptomatic relatives showed a combination of increased activation and a failure of deactivation in relation to alpha oscillations compared to healthy controls in the sensorimotor network.

Interpretation

Genetic factors may contribute to the shift in PAF and alterations in brain networks related to alpha oscillations. These may not entirely be a consequence of anti‐epileptic drugs, seizures or hippocampal sclerosis and deserve further investigation as mechanistic contributors to mTLE.
Dopant‐Free, Amorphous–Crystalline Heterophase SnO2Electron Transport Bilayer Enables >20% Efficiency in Triple‐Cation Perovskite Solar Cells
Authors: Lee Hock Beng , Kumar Neetesh , Ovhal Manoj Mayaji , Kim Yeong Jae , Song Young Min , Kang Jae‐Wook
Published: April 2020

Improving the ohmic contact and interfacial morphology between an electron transport layer (ETL) and perovskite film is the key to boost the efficiency of planar perovskite solar cells (PSCs). In the current work, an amorphous–crystalline heterophase tin oxide bilayer (Bi‐SnO2) ETL is prepared via a low‐temperature solution process. Compared with the amorphous SnO2sol–gel film (SG‐SnO2) or the crystalline SnO2nanoparticle (NP‐SnO2) counterparts, the heterophase Bi‐SnO2ETL exhibits improved surface morphology, considerably fewer oxygen defects, and better energy band alignment with the perovskite without sacrificing the optical transmittance. The best PSC device (active area ≈ 0.09 cm2) based on a Bi‐SnO2ETL is hysteresis‐less and achieves an outstanding power conversion efficiency of ≈20.39%, which is one of the highest efficiencies reported for SnO2‐triple cation perovskite system based on green antisolvent. More fascinatingly, large‐area PSCs (active areas of ≈3.55 cm2) based on the Bi‐SnO2ETL also achieves an extraordinarily high efficiency of ≈14.93% with negligible hysteresis. The improved device performance of the Bi‐SnO2‐based PSC arises predominantly from the improved ohmic contact and suppressed bimolecular recombination at the ETL/perovskite interface. The tailored morphology and energy band structure of the Bi‐SnO2has enabled the scalable fabrication of highly efficient, hysteresis‐less PSCs.
Low‐Dimensional Lead‐Free Inorganic Perovskites for Resistive Switching with Ultralow Bias
Authors: Ge Shuaipeng , Guan Xinwei , Wang Yutao , Lin Chun‐Ho , Cui Yimin , Huang Yunxia , Zhang Xinran , Zhang Ruoxuan , Yang Xiaoting , Wu Tom
Published: April 2020

3D organic–inorganic and all‐inorganic lead halide perovskites have been intensively pursued for resistive switching memories in recent years. Unfortunately, instability and lead toxicity are two foremost challenges for their large‐scale commercial applications. Dimensional reduction and composition engineering are effective means to overcome these challenges. Herein, low‐dimensional inorganic lead‐free Cs3Bi2I9 and CsBi3I10 perovskite‐like films are exploited for resistive switching memory applications. Both devices demonstrate stable switching with ultrahigh on/off ratios (≈106), ultralow operation voltages (as low as 0.12 V), and self‐compliance characteristics. 0D Cs3Bi2I9‐based device shows better retention time and larger reset voltage than the 2D CsBi3I10‐based device. Multilevel resistive switching behavior is also observed by modulating the current compliance, contributing to the device tunability. The resistive switching mechanism is hinged on the formation and rupture of conductive filaments of halide vacancies in the perovskite films, which is correlated with the formation of AgIx layers at the electrode/perovskite interface. This study enriches the library of switching materials with all‐inorganic lead‐free halide perovskites and offers new insights on tuning the operation of solution‐processed memory devices.
Micro/Nano Motor Navigation and Localization via Deep Reinforcement Learning
Authors: Yang Yuguang , Bevan Michael A. , Li Bo
Published: April 2020

Efficient navigation and precise localization of Brownian micro/nano self‐propelled motor particles within complex landscapes could enable future high‐tech applications involving for example drug delivery, precision surgery, oil recovery, and environmental remediation. Here, a model‐free deep reinforcement learning algorithm based on bio‐inspired neural networks is employed to enable different types of micro/nano motors to be continuously controlled to carry out complex navigation and localization tasks. Micro/nano motors with either tunable self‐propelling speeds or orientations or both, are found to exhibit strikingly different dynamics. In particular, distinct control strategies are required to achieve effective navigation in free space and obstacle environments, as well as under time constraints. The findings provide fundamental insights into active dynamics of Brownian particles controlled using artificial intelligence and could guide the design of motor and robot control systems to meet diverse application requirements.
Predictor of outcome after living donor liver transplantation for patients with hepatocellular carcinoma beyond the Japan criteria
Authors: Yonemura Yusuke , Yoshizumi Tomoharu , Inokuchi Shoichi , Kosai‐Fujimoto Yukiko , Harada Noboru , Itoh Shinji , Toshima Takeo , Takeishi Kazuki , Yoshiya Shohei , Mori Masaki
Published: April 2020

Background

The Japan criteria (JC, maximum tumor size within 5 cm, within five tumor nodules, AFP within 500 ng/mL or within Milan criteria) have been applied to cadaveric liver transplantation (LT) for hepatocellular carcinoma (HCC) and will be used for living donor LT (LDLT) in Japan. The aim of this study was to verify the JC in LDLT and to clarify the risk factor of HCC recurrence and mortality after LDLT beyond the JC.

Patients and methods

Adult patients who underwent LDLT for end‐stage liver disease with HCC until October 2019 were reviewed retrospectively (n = 246). Patients were divided into two groups according to whether they were within JC (n = 203) or beyond JC (n = 43). Recurrence‐free or overall survival rates after LDLT were compared. Univariate and multivariate analyses were performed to identify risk factors of HCC recurrence and HCC‐related mortality after LDLT for patients beyond the JC.

Results

Patients beyond the JC had significantly poorer 5‐year recurrence‐free (50.3% vs 95.9%, P < .001) or overall (61.7% vs 98.1%, P < .001) survival rates compared with patients within the JC. A multivariate analysis revealed that des‐gamma‐carboxy prothrombin (DCP) ≥ 300 mAU/mL (hazard ratio 9.36, 95% CI; 2.41‐36.4, P = .001) was an independent risk factor for HCC recurrence and HCC‐related mortality (hazard ratio 13.8, 95% CI; 1.92‐98.6, P = .01) after LDLT in patients beyond the JC.

Conclusion

The outcome of LDLT for patients within the JC was favorable. Patients beyond the JC with DCP ≥ 300 mAU/mL might be contraindicated for LDLT.
Synchronization of weaning time with peak fruit availability in squirrel monkeys (Saimiri collinsi) living in Amazonian Brazil
Authors: Stone Anita I. , Ruivo Luana V. P.
Published: April 2020

Many mammals coincide their reproductive activities with factors such as ambient temperature, rainfall, and food availability. In primates that invest immediate food intake into reproduction, the periods of maximum fruit production often coincide with the peak of lactation (to maximize maternal survival) or the occurrence of weaning (to maximize infant survival). This study investigates the relationship between reproductive periods and the availability of ripe fruit in the habitat of a population of wild squirrel monkeys (Saimiri collinsi) in Amazonian Brazil. We combine data from several years (2002–2003; 2011–2015) during which we followed the monkeys and quantified the occurrence of matings, gestations, births, and the number of lactating females. We also collected rainfall and plant phenological data for 24 months. Our results confirm that reproductive events are highly seasonal in S. collinsi. The period of weaning corresponded to the peak in the abundance of ripe fruits consumed by the monkeys. This indicates that the period of infant nutritional independence is optimally timed to coincide with periods of greater food production in this habitat. We suggest that seasonal breeding in these primates does not necessarily reduce maternal energetic stress, but likely improves infant survivorship.
Strontium, oxygen, and carbon isotope variation in modern human dental enamel
Authors: Plomp Esther , von Holstein Isabella C. C. , Kootker Lisette M. , Verdegaal‐Warmerdam Suzanne J. A. , Forouzanfar Tim , Davies Gareth R.
Published: April 2020

Objectives

Isotopic analyses using human dental enamel provide information on the mobility and diet of individuals in forensic and archeological studies. Thus far, no study has systematically examined intraindividual coupled strontium (Sr), oxygen (O), and carbon (C) isotope variation in human enamel or the effect that caries have on the isotopic integrity of the enamel. The inadequate quantification of isotopic variation affects interpretations and may constrain sample selection of elements affected by caries. This study aims to quantify the intraindividual isotopic variation and provides recommendations for enamel sampling methods.

Material and Methods

This study presents the first systematic results on intraindividual variation in Sr–O–C isotope composition and Sr concentration in modern human dental enamel of third molars (affected and unaffected by caries). A multiloci sampling approach (n = 6–20) was used to analyze surface and inner enamel, employing thermal ionization mass spectrometry (TIMS) and isotope ratio mass spectrometry (IRMS). Third molars were analyzed from 47 individuals from the Netherlands, Iceland, the United States, the Caribbean, Colombia, Somalia, and South Africa.

Results

Intradental isotopic variation in modern Dutch dental elements was recorded for Sr, O, and C and exceeded the variation introduced by the analytical error. Single loci and bulk sampling approaches of third molars established that a single analysis is only representative of the bulk Sr isotope composition in 60% of the elements analyzed. Dental elements affected by caries showed twice the variation seen in unaffected dental elements. Caries did not consistently incorporate the isotopic composition of the geographical environment in which they developed.

Discussion

The isotopic variability recorded in unaffected inner enamel indicates that variations greater than 0.000200 for 87Sr/86Sr and larger than 2‰ for δ18O and δ13C are required to demonstrate changes in modern Dutch human diet or geographic location.
Characterization and implications of the lingual process of the sphenoid bone: a cadaveric and radiographic study
Authors: Li Lifeng , London Nyall R. , Chen Xiaohong , Prevedello Daniel M. , Carrau Ricardo L.
Published: April 2020

Background

The surgical significance of the lingual process of the sphenoid bone (LPSB) has not been sufficiently addressed. The purpose of this study was to describe the anatomical details of the LPSB in relation to the quadrangular space. Moreover, the incidence of the LPSB and its correlation with the pneumatization of the sphenoid sinus and the development of the lateral recess of the sphenoid sinus (LRSS) were also evaluated.

Methods

A dissection and exposure of the LPSB and the quadrangular space was performed on 10 cadaveric specimens (20 sides). The incidence, length, and height of the LPSB were also assessed on computed tomography (CT) images (60 patients, 120 sides). The association between the presence of the LPSB with the pneumatization type of the sphenoid sinus and the presence of a LRSS was evaluated.

Results

In a cadaveric model, the LPSB, in association with the petrolingual ligament extending from the LPSB to the petrous apex, was identified on 7 sides (35%). The LPSB was continuous with the mandibular strut. The overall incidence of a LPSB was 48.33% on CT images, and the average length and height of the LPSB was (mean ± standard deviation) 5.30 ± 1.44 mm and 6.51 ± 1.32 mm, respectively. A significant correlation was identified between presence of the LPSB with the pneumatization type of the sphenoid sinus (p = 0.004) but no correlation was identified with the presence of the LRSS (p = 0.071).

Conclusion

The LPSB and the petrolingual ligament are useful landmarks for procedures in the quadrangular space and Meckel's cave. However, the LPSB is not consistently present.
Skull‐base surgery during the COVID‐19 pandemic: the Italian Skull Base Society recommendations
Authors: Castelnuovo Paolo , Turri‐Zanoni Mario , Karligkiotis Apostolos , Battaglia Paolo , Pozzi Fabio , Locatelli Davide ,   the Italian Skull Base Society Board, Italian Skull Base Society Board (Società Italiana Basicranio [SIB]), Bernucci Claudio , Iacoangeli Maurizio , Krengli Marco , Marchetti Marcello , Pareschi Roberto , Pompucci Angelo , Rabbiosi Dimitri
Published: April 2020

Severe acute respiratory syndrome‐coronavirus‐2 (SARS‐CoV‐2), which causes coronavirus disease 2019 (COVID‐19), is highly contagious with devastating impacts for healthcare systems worldwide. Medical staff are at high risk of viral contamination and it is imperative to know what personal protective equipment (PPE) is appropriate for each situation. Furthermore, elective clinics and operations have been reduced in order to mobilize manpower to the acute specialties combating the outbreak; appropriate differentiation between patients who require immediate care and those who can receive telephone consultation or whose treatment might viably be postponed is therefore crucial. Italy was 1 of the earliest and hardest‐hit European countries and therefore the Italian Skull Base Society board has promulgated specific recommendations based on consensus best practices and the literature, where available. Only urgent surgical operations are recommended and all patients should be tested at least twice (on days 4 and 2 prior to surgery). For positive patients, procedures should be postponed until after swab test negativization. If the procedure is vital to the survival of the patient, filtering facepiece 3 (FFP3) and/or powered air purifying respirator (PAPR) devices, goggles, full‐face visor, double gloves, water‐resistant gowns, and protective caps are mandatory. For negative patients, use of at least an FFP2 mask is recommended. In all cases the use of drills, which promote the aerosolization of potentially infected mucous particles, should be avoided. Given the potential neurotropism of SARS‐CoV‐2, dura handling should be minimized. It is only through widely‐agreed protocols and teamwork that we will be able to deal with the evolving and complex implications of this new pandemic.
An update on memory formation and retrieval: An engram‐centric approach
Authors: Bostancıklıoğlu Mehmet
Published: April 2020

Objective

We explore here that memory loss observed in the early stage of Alzheimer's disease (AD) is a disorder of memory retrieval, instead of a storage impairment. This engram‐centric explanation aims to enlarge the conceptual frame of memory as an emergent behavior of the brain and to propose a new treatment strategy for memory retrieval in dementia‐AD.

Background

The conventional memory hypothesis suggests that memory is stored as multiple traces in hippocampal neurons but recent evidence indicates that there are specialized memory engrams responsible for the storage and the retrieval of different memory types.

Updated Memory Hypothesis

There are specialized memory engram neurons for each memory type and when information will be stored as a memory arrives in the hippocampus through afferent neurons finds its neuron according to the excitability states of engram neurons. The excitability level in engram neurons seems like a code canalizing the interactions between engrams and information. Therefore, to enhance the excitability of memory engram neurons improves memory loss observed in AD. In addition, we suggest that the hippocampus creates an index for information stored in memory engram cells in specialized regions for different types of memory, instead of storing all information; and different anatomic locations of engram cells and their roles in memory retrieval point out that memory could be an emergent behavior of the brain, and the interaction between serotonin fluctuation and engram neurons could be neural underpinnings of terminal lucidity.

Major Challenges for the Model

The major challenge for this engram‐centric memory retrieval model is the translation from bench to patient, specifically the delivery of optogenetic tools in patients. Engram neurons can be specifically activated by optogenetic tools, but optogenetics is an invasive technique which requires optic fiber implantation into the brain. In addition, light can overheat the tissue and thus induce damage in tissue. Furthermore, light is a foreign object and its direct implantation into the brain may cause neuroinflammation, the main trigger of neurodegenerative diseases. Therefore, to test the engram hypothesis in human, new tools to allow specific engram activation should be discovered.
Graphdiyne Interface Engineering: Highly Active and Selective Ammonia Synthesis
Authors: Fang Yan , Xue Yurui , Li Yongjun , Yu Huidi , Hui Lan , Liu Yuxin , Xing Chengyu , Zhang Chao , Zhang Danyan , Wang Zhongqiang , Chen Xi , Gao Yang , Huang Bolong , Li Yuliang
Published: April 2020

A freestanding 3D graphdiyne–cobalt nitride (GDY/Co2N) with a highly active and selective interface is fabricated for the electrochemical nitrogen reduction reaction (ECNRR). Density function theory calculations reveal that the interface‐bonded GDY contributes an unique p‐electronic character to optimally modify the Co‐N compound surface bonding, which generates as‐observed superior electronic activity for NRR catalysis at the interface region. Experimentally, at atmospheric pressure and room temperature, the electrocatalyst creates a new record of ammonia yield rate (Y
) and Faradaic efficiency (FE) of 219.72 μg h−1 mgcat.−1 and 58.60 %, respectively, in acidic conditions, higher than reported electrocatalysts. Such a catalyst is promising to generate new concepts, new knowledge, and new phenomena in electrocatalytic research, driving rapid development in the field of electrocatalysis.
Non‐catalytic and heterogeneous acid/base‐catalyzed biodiesel production: Recent and future developments
Authors: Tran‐Nguyen Phuong Lan , Ong Lu Ki , Go Alchris Woo , Ju Yi‐Hsu , Angkawijaya Artik Elisa
Published: April 2020

Biodiesel production technologies, which are non‐catalytic and those involving the use of heterogeneous catalyst(s), have gained much interest owing to its high biodiesel and pure glycerol throughput. During the past 15 years, many studies were devoted to explore new catalysts as well as improve non‐catalytic technologies with aims to ultimately industrialize such biodiesel production processes. This review elucidates the main process parameters that influences non‐catalytic and heterogeneous‐catalyzed biodiesel production processes. The common parameters among these technologies include the process temperature, alcohol/oil molar ratio, pressure, catalyst loading, and feedstock quality. Optimization of these process parameters is discussed according to the use of conventional method (one factor at a time [OFAAT]) or the use of statistical methods such as response surface methodology (RSM), artificial neural network (ANN), and Taguchi method. In addition, recent development on non‐catalytic process and those involving the use of heterogeneous catalyst(s), such as glycerol‐free processes under supercritical conditions of alkyl donors and strategies to improve properties of heterogeneous catalyst, are also reviewed. Finally, insight based on the published techno‐economical evaluations is also tackled, and future prospects and research directions on these technologies are also discussed.
A biosensor platform based on amine functionalized conjugated benzenediamine‐benzodithiophene polymer for testosterone analysis
Authors: Bulut Umut , Sanli Serdar , Cevher Sevki Can , Cirpan Ali , Donmez Sude , Timur Suna
Published: April 2020

A novel benzenediamine‐benzodithiophene polymer is synthesized for use in biosensor fabrication for the detection of testosterone. The sensory platform is constructed via drop coating on a screen‐printed carbon electrode, using poly(benzenediamine‐Bis[(2‐ethylhexyl)oxy]benzodithiophene) (pBDBT) as the polymer layer. Testosterone antibodies are immobilized on the polymer‐coated electrode surface via glutaraldehyde, which binds to the surface through the amino functional groups on the polymer backbone. The changes in the surface features due to testosterone binding are investigated via electrochemical techniques such as differential pulse voltammetry, cyclic voltammetry, and electrochemical impedance spectrometry as well as contact angle measurements. Surface morphology of the modified electrodes is characterized by atomic force microscopy. The linear range and limit of detection of the sensor are calculated. Impact of possible interfering compounds is investigated. Furthermore, the sensory platform is utilized for testosterone analysis in synthetic biological fluids.
Homopolymerization of styrenic monomers and their copolymerization with ethylene using group 4 non‐metallocene catalysts
Authors: Białek Marzena , Fryga Julia
Published: April 2020

Homopolymerization of styrenic monomers (St, p‐Me‐St, p‐tBu‐St, p‐tBuO‐St) and their copolymerization with ethylene, with the use of [(tBu2O2NN′)ZrCl]2(μ‐O) (1) and (tBu2O2NN′)TiCl2 (2), where tBu2O2NN′ = Me2N(CH2)2N(CH2‐2‐O−‐3,5‐tBu2‐C6H2)2, is explored in the presence of MMAO and (iBu)3Al/Ph3CB(C6F5)4. The ethylene/styrenic monomers copolymerization with 1/MMAO produces exclusively copolymers with high activity and good comonomer incorporation whereas the other catalytic systems yield mixtures of copolymers and homopolymers. The use of p‐alkyl styrene derivatives instead of styrene raises the catalytic activity, comonomer incorporation and molecular weights of the copolymers. Complex 2 exhibits higher activity in homopolymerization of styrenic monomers than 1 irrespective of the kind of the activator employed. A clear dependence is observed for the molecular weight and catalyst activity against the kind of the styrenic monomer. The obtained polymers were atactic and only the complex 2, when activated by MMAO, promoted the highly syndiospecific polymerization of p‐Me‐St and p‐tBu‐St. Poly(p‐tBuO‐St) exhibits fiber‐forming properties.
Biomarkers of minimal residual disease in rituximab‐treated patients with mixed cryoglobulinemia
Authors: Basile Umberto , Gulli Francesca , Napodano Cecilia , Pocino Krizia , Basile Valerio , Marrapodi Ramona , Colantuono Stefania , Todi Laura , Marino Mariapaola , Rapaccini Gian Ludovico , Visentini Marcella
Published: April 2020

Hepatitis C virus (HCV) represents the major risk factor for mixed cryoglobulinemia (MC), a small‐vessel vasculitis that may evolve into an overt B‐cell non‐Hodgkin's lymphoma. Here, we aimed to identify a biomarker signature for the early diagnosis of minimal residual disease (MRD). We assessed free light chains (FLCs), IgM k,and IgM λ heavy/light chain (HLC) pairs, and vascular endothelial growth factor (VEGF) in sera from 34 patients with MC vasculitis (32 HCV‐ and 2 HBV‐related), treated with low‐dose rituximab (RTX). FLCs and IgM HLCs were measured by turbidimetric assay; VEGF by an enzyme‐linked immunosorbent assay. After RTX, the positive (complete + partial) clinical and laboratory responses were of 85.29% and 50%, respectively; in contrast, the mean levels of FLCs, IgM HLCs, and VEGF were substantially unaffected in most patients and still above the normal range. In those achieving a reduction of FLCs and IgM k and λ chains values within the range of normality, we found that post‐treatment free λ chains and IgM k values correlated with clinical and laboratory response. Our results suggest that high levels of FLCs, IgM HLCs, and VEGF could represent the signature of “dormant” B cell clones’ activity that could be very useful to identify MRD indicative of possible relapse or worsening outcome.
Demonstration‐scale enzymatic saccharification of sulfite‐pulped spruce with addition of hydrogen peroxide for LPMO activation
Authors: Costa Thales H. F. , Kadic' Adnan , Chylenski Piotr , Várnai Anikó , Bengtsson Oskar , Lidén Gunnar , Eijsink Vincent G.H. , Horn Svein Jarle
Published: April 2020

The saccharification of lignocellulosic materials like Norway spruce is challenging due to the recalcitrant nature of the biomass, and it requires optimized and efficient pretreatment and enzymatic hydrolysis processes to make it industrially feasible. In this study, we report successful enzymatic saccharification of sulfite‐pulped spruce (Borregaard's BALI™ process) at demonstration scale, achieved through the controlled delivery of hydrogen peroxide (H2O2) for the activation of lytic polysaccharide monooxygenases (LPMOs) present in the cellulolytic enzyme preparation. We achieved 85% saccharification yield in 4 days using industrially relevant conditions – that is, an enzyme dose of 4% (w/w dry matter of substrate) of the commercial cellulase cocktail Cellic CTec3 and a substrate loading of 12% (w/w). Addition of H2O2 and the resulting controlled and high LPMO activity had a positive effect on the rate of saccharification and the final sugar titer. Clearly, the high LPMO activity was dependent on feeding the reactors with the LPMO co‐substrate H2O2, as in situ generation of H2O2 from molecular oxygen was limited. These demonstration‐scale experiments provide a solid basis for the use of H2O2 to improve enzymatic saccharification of lignocellulosic biomass at large industrial scale.© 2020 The Authors. Biofuels, Bioproducts, and Biorefining published by Society of Chemical Industry and John Wiley & Sons, Ltd.
Synthesis, spectral properties and antimicrobial activity of a new cationic water‐soluble pH‐dependent poly(propylene imine) dendrimer modified with 1,8‐naphthalimides
Authors: Staneva Desislava , Manov Hristo , Yordanova Stanislava , Vasileva‐Tonkova Evgenia , Stoyanov Stanimir , Grabchev Ivo
Published: April 2020

A three‐step synthesis was implemented to prepare a quaternary ammonium functionalized blue fluorescent poly(propylene imine) dendrimer modified with pyridinium salt of 4‐acylamino‐1,8‐naphthalimide. The new cationic dendrimer absorbs in the ultraviolet light region and emits blue fluorescence. Its spectral characteristics in organic solvents and in an aqueous solution were studied. The influence of pH on the fluorescence intensity of the dendrimer was established with regard to its use as a pH sensor. The effect of hydroxyl ions on the absorption and fluorescence spectra in dry N,N‐dimethylformamide was also investigated. The antimicrobial activity of the dendrimer was assessed against model pathogenic microorganisms in agar, liquid medium, and after its deposition on cotton fabric.
Anything but Conventional Chromatography Approaches in Bioseparation
Authors: Roque Ana Cecília Afonso , Pina Ana Sofia , Azevedo Ana Margarida , Aires‐Barros Raquel , Jungbauer Alois , Di Profio Gianluca , Heng Jerry Y. Y. , Haigh Jonathan , Ottens Marcel
Published: April 2020

While packed bed chromatography, known as conventional chromatography, has been serving the biopharmaceutical industry for decades as the bioseparation method of choice, alternative approaches are likely to take an increasing leading role in the next few years. The high number of new biological drugs under development, and the need to make biopharmaceuticals widely accessible, has been driving the academia and industry in the quest of anything but conventional chromatography approaches. In this perspective paper, these alternative approaches are discussed in view of current and future challenges in the downstream processing field.
Current technologies to endotoxin detection and removal for biopharmaceutical purification
Authors: Schneier Mason , Razdan Sidharth , Miller Allison M. , Briceno Maria E. , Barua Sutapa
Published: April 2020

Endotoxins are the major contributors to the pyrogenic response caused by contaminated pharmaceutical products, formulation ingredients, and medical devices. Recombinant biopharmaceutical products are manufactured using living organisms, including Gram‐negative bacteria. Upon the death of a Gram‐negative bacterium, endotoxins (also known as lipopolysaccharides) in the outer cell membrane are released into the lysate where they can interact with and form bonds with biomolecules, including target therapeutic compounds. Endotoxin contamination of biologic products may also occur through water, raw materials such as excipients, media, additives, sera, equipment, containers closure systems, and expression systems used in manufacturing. The manufacturing process is, therefore, in critical need of methods to reduce and remove endotoxins by monitoring raw materials and in‐process intermediates at critical steps, in addition to final drug product release testing. This review paper highlights a discussion on three major topics about endotoxin detection techniques, upstream processes for the production of therapeutic molecules, and downstream processes to eliminate endotoxins during product purification. Finally, we have evaluated the effectiveness of endotoxin removal processes from a perspective of high purity and low cost.
Brain volumes in relation to loneliness and social competence in preadolescents born very preterm
Authors: Lind Annika , Salomäki Susanna , Parkkola Riitta , Haataja Leena , Rautava Päivi , Junttila Niina , Koikkalainen Juha , Lötjönen Jyrki , Saunavaara Virva , Korja Riikka ,   PIPARI Study Group
Published: April 2020

Introduction

The aim of the present study was to assess how regional brain volumes associate with self‐experienced social and emotional loneliness and social competence in very preterm and term‐born preadolescents.

Materials and methods

Thirty‐four very preterm subjects (birthweight ≤1,500 g and/or gestational age <32 weeks) without neurodevelopmental impairments and/or major brain pathologies and 31 term‐born subjects underwent magnetic resonance imaging at 12 years of age. Regional brain volumes were measured using an automated image quantification tool. At 11 years of age, social and emotional loneliness were assessed with the Peer Network and Dyadic Loneliness Scale‐self‐report questionnaire and cooperating skills, empathy, impulsivity, and disruptiveness with the Multisource Assessment of Children's Social Competence Scale‐self‐report questionnaire.

Results

In the very preterm group, a number of significant associations were found between smaller regional brain volumes and self‐experienced emotional loneliness, more impulsivity and more disruptiveness. In the control group, brain volumes and loneliness were not associated, and brain volumes and social competence were associated with a lesser degree than in the very preterm group.

Conclusion

Experiences of emotional loneliness and poorer social competence appear to be more related to brain volumes in very preterm preadolescents than in those born full‐term. It also appears that in very preterm preadolescents, emotional loneliness may be more reflected in brain development than social loneliness.
Harnessing the patient voice in prostate cancer research: Systematic review on the use of patient‐reported outcomes in randomized controlled trials to support clinical decision‐making
Authors: Van Hemelrijck Mieke , Sparano Francesco , Moris Lisa , Beyer Katharina , Cottone Francesco , Sprangers Mirjam , Efficace Fabio
Published: April 2020

Background

Given the growing importance of patient‐reported outcomes (PROs) as part of “big data” in improving patient care, there is a need to provide a state‐of‐the‐art picture of the added value of using PROs in prostate cancer (PCa) randomized controlled trials (RCTs). We aimed to synthetize the most recent high‐quality PRO evidence‐based knowledge from PCa RCTs and to examine whether quality of PRO reporting in PCa research improved over time.

Methods

We conducted a systematic literature search using PubMed, from April 2012 until February 2019. For benchmarking purposes, we also included RCTs identified in our previously published review of RCTs (2004‐2012). Methodology for study identification and evaluation followed standardized criteria and a predefined data extraction form was used to abstract information. PRO quality of the studies was evaluated using the International Society of Quality of Life Research (ISOQOL) recommended criteria.

Results

A total of 55 new RCTs were published between April 2012 and February 2019. About 24 (43.6%) RCTs were found to be of high‐quality regarding PRO assessments. Of these, 13 (54.2%) have been reported in the most recent European Association of Urology (EAU) PCa Guidelines. Overall QoL and sexual, urinary, and bowel function were the most commonly reported PROs. FACT‐P, EPIC‐26, and EORTC QLQ‐C30 and/or its module PR25 were most frequently used as measurement tools. An overall improvement in the completeness of PRO reporting was noted over time.

Conclusion

Many PRO trials are currently not included in the EAU guidelines. Our findings suggest that there has to be a better consensus on the use of PRO data for PCa patients, which will then be reflected in the PCa Guidelines and future data collection. Homogeneity in PROs collection and measurement tools will in turn enable “big data” Consortia to increase the patients’ voice in clinical research.