bluuebunny/crossref_metadata_2025 huggingface dataset:
Feasible outcome of blinatumomab followed by allogeneic hematopoietic cell transplantation for adults with Philadelphia chromosome‐negative acute lymphoblastic leukemia in first salvage
Authors: Yoon Jae‐Ho , Min Gi June , Park Sung‐Soo , Park Silvia , Lee Sung‐Eun , Cho Byung‐Sik , Eom Ki‐Seong , Kim Yoo‐Jin , Kim Hee‐Je , Min Chang‐Ki , Cho Seok‐Goo , Kim Dong‐Wook , Lee Jong Wook , Lee Seok
Published: November 2019

In adult patients with relapsed or refractory (R/R) Philadelphia chromosome‐negative (Ph‐negative) B‐cell presursor acute lymphoblastic leukemia (BCP‐ALL), complete remission (CR) and overall survival (OS) rates are poor. We analyzed treatment outcomes and prognostic factors for 32 adult patients with R/R Ph‐negative BCP‐ALL who received blinatumomab at first salvage. Patients who achieved CR proceeded to allogeneic hematopoietic cell transplantation (allo‐HCT). At the time of blinatumomab treatment, 11 patients (34.3%) were primary refractory, 10 (31.4%) had relapsed with first CR duration (CRD1) ≥12 months, and 11 (34.3%) had relapsed with CRD1 <12 months. After the first blinatumomab cycle, 22 (68.8%) achieved CR. At the end of the second cycle, 20 of the 22 patients remained in persistent CR, and 1 patient achieved new CR. The overall minimal residual disease negativity rate was 75% among evaluable patients with persistent CR. Patients with CRD1 <12 months were associated with poorer response to blinatumomab. Twenty (62.5%) of 32 patients underwent allo‐HCT in blinatumomab‐induced CR. After a median follow‐up of 15.2 months, the 1‐year OS rates for all patients and patients receiving allo‐HCT in CR were 55.5% (median OS, 18.2 months) and 70.7%, respectively. Patients with CRD1 <12 months, extramedullary disease (EMD), and high peripheral blood blasts were associated with poorer OS. Blinatumomab is effective for achieving good quality CR and bridging to allo‐HCT for adult patients with R/R Ph‐negative BCP‐ALL in first salvage. The role of blinatumomab in patients with CRD1 <12 months, EMD, or high tumor burden should be evaluated in future trials.
Clinical characteristics, diagnosis, treatment, and prognostic factors of pulmonary mucosa‐associated lymphoid tissue‐derived lymphoma
Authors: Wang Lin , Ye Guanzhi , Liu Zhonghe , Shi Lin , Zhan Cheng , Gu Jie , Luo Rongkui , Lin Zongwu , Ge Di , Wang Qun
Published: November 2019

Primary pulmonary mucosa‐associated lymphoid tissue‐derived (MALT) lymphoma is a rare disease with a favorable prognosis. However, its clinical characteristics, diagnosis, treatment, and prognoses remain unclear. We retrospectively analyzed 80 patients with pathologically confirmed MALT lymphoma from 2006 to 2018. The clinical characteristics, diagnosis, treatments, and prognoses of all the 80 patients were recorded. Patients were stratified into surgery and biopsy groups, respectively, to evaluate the role of surgery in the diagnosis and treatment of MALT lymphoma. The prognoses were compared between different clinical characteristics and treatments. Pathological diagnoses were confirmed by surgery, bronchoscopy, and percutaneous biopsy. Thirty patients were treated by surgery. While MALT lymphoma was only diagnosed by bronchofiberoscopy or bercutaneous biopsy in four of 18 patients in the surgery group who underwent the procedure. Six patients received adjuvant chemotherapy and one patient received involved‐field radiotherapy in surgery group. Thirty‐one patients were treated with chemotherapy alone, one patient was treated with radiotherapy, one patient received only symptomatic and supportive treatment, and waiting and watching without treatment were recommended in 17 patients in biopsy group. Eight patients died during follow‐up and the 5‐year survival rate was 87.1%. Tumor number, treatment, and age were prognostic factors for overall survival (OS), but age was the only independent prognostic factor according to multivariate analysis. While, tumor number was the only prognostic factor in the analysis about progression‐free survival (PFS). No significant difference was found in OS or PFS between patients treated with and without surgical resection. MALT lymphoma is an indolent disease with favorable treatment outcome. Tumor number is associated with PFS and age is the only significant prognostic factor for pulmonary MALT lymphoma patients because of its indolent nature, but surgery still plays an important role in the diagnosis and treatment of MALT lymphoma.
Chemical Composition of Ambrosia trifida Essential Oil and Phytotoxic Effect on Other Plants
Authors: Sarić‐Krsmanović Marija , Umiljendić Jelena Gajić , Radivojević Ljiljana , Rajković Miloš , Šantrić Ljiljana , Đurović‐Pejčev Rada
Published: November 2019

This study aimed to identify the main components of an essential oil produced from leaves of Ambrosia trifida and to evaluate its potential allelopathic effect on seed germination and seedling growth of lettuce, watermelon, cucumber and tomato. The essential oil was obtained by hydrodistillation and characterized chemically by gas chromatography (GC) coupled with both mass spectrometry (MS) and flame ionization detector (FID). Total 69 compounds were identified, with limonene (20.7 %), bornyl acetate (15.0 %), borneol (14.7 %) and germacrene D (11.6 %) as the major components. The working solutions of the essential oil emulsified with Tween 20 and dissolved in distilled water were prepared at four concentration levels (0.01, 0.1, 0.5 % and 1 %, v/v). The results obtained showed that increase in essential oil concentration leads to decrease in seed germination, as well as shoot and radical length of lettuce, watermelon, cucumber and tomato. The obtained data revealed a highly significant effect (p<0.05) between control and 1 % and 0.5 % oil concentrations in all treatments. The essential oil of A. trifida exhibited more powerful phytotoxic effects on lettuce, watermelon and tomato than on cucumber regarding germination and early seedling growth.
AMPK α1 mediates the protective effect of adiponectin against insulin resistance in INS‐1 pancreatic β cells
Authors: Wang Yan , Li Yan , Qiao Jing , Li Na , Qiao Shun
Published: November 2019

The fat‐derived protein adiponectin is known to reverse the effects of insulin resistance and to lower blood glucose levels. The AMP‐activated protein kinase (AMPK) signalling pathway plays a central role in metabolism and energy homeostasis. Here, to investigate the role of AMPK in the protective effect of adiponectin against insulin resistance, we established the model of high‐glucose (HG)‐ and high‐lipid (HL)‐induced insulin resistance in INS‐1 pancreatic β cells. We found that 25mM of glucose and 0.4mM of palmitic acid treatment significantly increased cell apoptosis and impaired insulin secretion in INS‐1 cells. However, recombinant human adiponectin dramatically reduced HG‐ and/or HL‐induced cell apoptosis and greatly improved insulin secretion. Interestingly, adiponectin treatment also activated AMPK signalling pathway by increasing the phosphorylation of Thr172 in the AMPK α subunit; 10μM of compound C, a potent AMPK inhibitor, blocked the protective effects of adiponectin against HG/HL‐induced insulin resistance. Furthermore, knockout experiments by CRISPR/Cas9 technology showed that AMPK α1, but not AMPK α2, is involved in the protective effects of adiponectin. Taken together, adiponectin reversed the effects of insulin resistance via AMPK α1, which provides a novel insight into the protective mechanism of adiponectin and may be used as a new strategy for the treatment of type 2 diabetes.

Significance of the Study

Adiponectin can reverse the effects of insulin resistance and lower blood glucose levels. Here, adiponectin reduced HG/HL‐induced cell apoptosis and greatly improved insulin secretion. These effects were blocked by AMPK inhibitor, compound C. Specifically, we found that AMPK α1, but not AMPK α2, mediates the protective effects of adiponectin, which provides a novel insight into the protective mechanism of adiponectin against insulin resistance.
Myricetin ameliorates high glucose‐induced endothelial dysfunction in human umbilical vein endothelial cells
Authors: Aminzadeh Azadeh , Bashiri Hamideh
Published: November 2019

Endothelial dysfunction is recognized as the initial detectable stage of cardiovascular disease, a serious complication of diabetes. In this study, we evaluated effects of myricetin on high glucose (HG)‐elicited oxidative damage in human umbilical vein endothelial cells (HUVECs). The cells were pre‐incubated with myricetin and then treated with HG to induce apoptosis. The effect of myricetin on viability was investigated by MTT assay. The levels of lipid peroxidation (LPO) were determined by thiobarbituric acid (TBA) method. The protein expression of Bax, Bcl‐2 and caspase‐3 was measured by western blot analysis. Moreover, the effect of myricetin on total antioxidant capacity (TAC) and total thiol molecules was also determined. Our results showed that myricetin was able to markedly restore the viability of endothelial cells under oxidative stress. Myricetin reduced HG‐caused increase in LPO levels. Also, TAC and total thiol molecules were notably elevated by myricetin. Incubation with myricetin decreased the protein expression levels of Bax, whereas it increased the expression levels of the Bcl‐2, compared with HG treatment alone. Furthermore, myricetin significantly decreased cleaved caspase‐3 protein expression. It is concluded that myricetin may protect HUVECs from oxidative stress induced by HG via increasing cell TAC and reducing Bax/Bcl‐2 protein ratio, and caspase‐3 expression.
Chemical Methods for N‐ and O‐Sulfation of Small Molecules, Amino Acids and Peptides
Authors: Benedetti Anna Mary , Gill Daniel M. , Tsang Chi W. , Jones Alan M.
Published: November 2019

Sulfation of the amino acid residues of proteins is a significant post‐translational modification, the functions of which are yet to be fully understood. Current sulfation methods are limited mainly to O‐tyrosine (sY), which requires negatively charged species around the desired amino acid residue and a specific sulfotransferase enzyme. Alternatively, for solid‐phase peptide synthesis, a de novo protected sY is required. Therefore, synthetic routes that go beyond O‐sulfation are required. We have developed a novel route to N‐sulfamation and can dial‐in/out O‐sulfation (without S‐sulfurothiolation), mimicking the initiation step of the ping‐pong sulfation mechanism identified in structural biology. This rapid, low‐temperature and non‐racemising method is applicable to a range of amines, amides, amino acids, and peptide sequences.
SnO2@MoO2/Carbon Ternary Hollow Nanocomposites with Robust Shell as High‐Performance Lithium‐Ion‐Battery Anodes
Authors: Wang Yong , Mao Peiyuan , Rao Shun , Guo Wenbin , Zhang Fanchao , Xiao Pandeng , Zhang Wen
Published: November 2019

SnO2@MoO2/carbon hollow nanospheres are successfully fabricated by coating a Mo‐polydopamine chelate precursor on SiO2@SnO2 nanospheres, with subsequent annealing and HF corrosion. In the unique nanocomposites, the external carbon layer with MoO2 nanoparticles and a SnO2 hollow inner layer as the skeleton can not only enhance electronic conductivity, but also reinforce the shell of the hollow nanocomposites while preventing the aggregation of SnO2 and MoO2 nanoparticles during intensive cycles, thus enhancing the structural integrity, rate capability and cyclic stability. In virtue of the respective roles and synergistic effects of the three nanocomponents, the unique ternary nanocomposites possess an initial discharge capacity of 1097 mAhg−1, high initial coulombic efficiency of 85 %, and good cyclic performance (725 mAhg−1 after 300 cycles) as anode nanomaterials. The structural design of the MoO2/C layer coating metal‐oxide hollow nanospheres can provide a novel synthetic approach for other hybrid energy nanomaterials with excellent properties.
Synthesis and Biological Activity of Short Interfering RNAs Having Several Consecutive Amide Internucleoside Linkages
Authors: Kotikam Venubabu , Viel Julien A. , Rozners Eriks
Published: November 2019

The success of RNA interference (RNAi) as a research tool and potential therapeutic approach has reinvigorated interest in chemical modifications of RNA. Replacement of the negatively charged phosphates with neutral amides may be expected to improve bioavailability and cellular uptake of small interfering RNAs (siRNAs) critical for in vivo applications. In this study, we introduced up to seven consecutive amide linkages at the 3′‐end of the guide strand of an siRNA duplex. Modified guide strands having four consecutive amide linkages retained high RNAi activity when paired with a passenger strand having one amide modification between its first and second nucleosides at the 5′‐end. Further increase in the number of modifications decreased the RNAi activity; however, siRNAs with six and seven amide linkages still showed useful target silencing. While an siRNA duplex having nine amide linkages retained some silencing activity, the partial reduction of the negative charge did not enable passive uptake in HeLa cells. Our results suggest that further chemical modifications, in addition to amide linkages, are needed to enable cellular uptake of siRNAs in the absence of transfection agents.
A Simple Nickel Catalyst Enabling anE‐Selective Alkyne Semihydrogenation
Authors: Thiel Niklas O. , Kaewmee Benyapa , Tran Ngoc Trung , Teichert Johannes F.
Published: November 2019

Stereoselective alkyne semihydrogenations are attractive approaches to alkenes, which are key building blocks for synthesis. With regards to the most atom‐economic reducing agent dihydrogen (H2), only few catalysts for the challengingE‐selective alkyne semihydrogenation have been disclosed, each with a unique substrate scope profile. Here, we show that a commercially available nickel catalyst facilitates theE‐selective alkyne semihydrogenation of a wide variety of substituted internal alkynes. This results in a simple and broadly applicable overall protocol to stereoselectively accessE‐alkenes employing H2, which could serve as a general method for synthesis.
Quantum Mechanics/Molecular Mechanics Studies of the Mechanism of Cysteine Proteases Inhibition by Dipeptidyl Nitroalkenes
Authors: Arafet Kemel , González Florenci V. , Moliner Vicent
Published: November 2019

In this work a computational study of the mechanism of inhibition of cruzain, rhodesain, and cathepsin L cysteine proteases by the dipeptidyl nitroalkene Cbz‐Phe‐Ala‐CH=CH‐NO2 has been carried out by means of molecular dynamics simulations with hybrid QM/MM potentials. The free‐energy surfaces confirmed that the inhibition takes place by the formation of a covalent bond between the protein and the β‐carbon atom of the inhibitor. According to the results, the tested inhibitor should be a much more efficient inhibitor of cruzain than of rhodesain, and little activity would be expected against cathepsin L, in total correspondence with the available experimental data. The origin of these differences may lie in the different stabilizing electrostatic interactions established between the inhibitor and the residues of the active site and S2 pocket of these enzymes. These results may be useful for the rational design of new dipeptidyl nitroalkenes with higher and more selective inhibitory activity against cysteine proteases.
Atrial fibrillation‐related stroke in women: Evidence and inequalities in epidemiology, mechanisms, clinical presentation, and management
Authors: Kostopoulou Anna , Zeljko Hrvojka M. , Bogossian Harilaos , Ciudin Radu , Costa Francisco , Heijman Jordi , Kochhaeuser Simon , Manola Sime , Scherr Daniel , Sohal Manav , Wakili Reza , Wolf Michael , Irfan Ghazala ,   on the behalf of the DAS‐CAM participants—2017‐2018
Published: November 2019

Background

Atrial fibrillation (AF) is the most common clinical arrhythmia and one of the major causes of stroke, heart failure, sudden death, and cardiovascular morbidity. Despite substantial advances in (interventional) rhythm control treatment during the last decade, anticoagulation for stroke prevention remains a major component of AF treatment.

Hypothesis

There are important sex‐specific differences in AF‐related stroke, resulting from sex‐specific mechanisms and therapeutic differences.

Methods

This review summarizes available data on sex differences in risk assessment and prevention of stroke and highlights current knowledge gaps in AF‐related stroke mechanisms, prevention and management that warrant further research.

Results

Increased thrombotic risk in women is multifactorial, involving hormonal changes after menopause, structural, endocrine and lifestyle/social factors and their interactions. It is clear from randomized studies that women benefit from anticoagulant treatment and that their bleeding risk is similar to men. Women should therefore receive equivalent treatment to men, based on the validated criteria for anticoagulation therapy. However, women are not represented equally in the large randomized studies and sex‐related information in many fields is lacking.

Conclusions

Female sex is an established risk factor for stroke in AF patients. The evidence for sex‐specific differences in stroke risk assessment and stroke prevention is accumulating. However, the underlying biological mechanisms remain incompletely understood and further studies are required in order to decrease AF‐related morbidity and mortality.
Proline‐Rich Peptides with Improved Antimicrobial Activity against E. coli, K. pneumoniae, and A. baumannii
Authors: Mardirossian Mario , Sola Riccardo , Beckert Bertrand , Collis Dominic W. P. , Di Stasi Adriana , Armas Federica , Hilpert Kai , Wilson Daniel N. , Scocchi Marco
Published: November 2019

Proline‐rich antimicrobial peptides (PrAMPs) are promising agents to combat multi‐drug resistant pathogens due to a high antimicrobial activity, yet low cytotoxicity. A library of derivatives of the PrAMP Bac5(1–17) was synthesized and screened to identify which residues are relevant for its activity. In this way, we discovered that two central motifs ‐PIRXP‐ cannot be modified, while residues at N‐ and C‐ termini tolerated some variations. We found five Bac5(1–17) derivatives bearing 1–5 substitutions, with an increased number of arginine and/or tryptophan residues, exhibiting improved antimicrobial activity and broader spectrum of activity while retaining low cytotoxicity toward eukaryotic cells. Transcription/translation and bacterial membrane permeabilization assays showed that these new derivatives still retained the ability to strongly inhibit bacterial protein synthesis, but also acquired permeabilizing activity to different degrees. These new Bac5(1–17) derivatives therefore show a dual mode of action which could hinder the selection of bacterial resistance against these molecules.
Biomarkers for immune checkpoint inhibition in non–small cell lung cancer (NSCLC)
Authors: Bodor J. Nicholas , Boumber Yanis , Borghaei Hossein
Published: November 2019

The emergence of immunotherapy has dramatically changed how non–small cell lung cancer is treated, and longer survival is now possible for some patients, even those with advanced disease. Although some patients achieve durable responses to checkpoint blockade, not all experience such benefits, and some suffer from significant immunotoxicities. Given this, biomarkers that predict response to therapy are essential, and testing for tumor programmed death ligand 1(PD‐L1) expression is the current standard. The extent of PD‐L1 expression determined by immunohistochemistry (IHC) has demonstrated a correlation with treatment response, although limitations with this marker exist. Recently, tumor mutational burden has emerged as an alternative biomarker, and studies have demonstrated its utility, irrespective of the PD‐L1 level of a tumor. Gene expression signatures, tumor genotype (such as the presence of an oncogenic driver mutation), as well as the density of tumor‐infiltrating lymphocytes in the tumor microenvironment also seem to affect response to immunotherapy and are being researched. Peripheral serum markers are being studied, and some have demonstrated predictive ability, although most are still investigational and need prospective validation. In the current article, the authors review the biomarker PD‐L1 as well as other emerging and investigational tissue‐based and serum‐based markers that have potential to better predict responders to immunotherapy.
Prospective development of a patient‐reported outcomes instrument for desmoid tumors or aggressive fibromatosis
Authors: Gounder Mrinal M. , Maddux LeAnne , Paty Jean , Atkinson Thomas M.
Published: November 2019

Background

Desmoid tumors (or aggressive fibromatosis) are locally infiltrative connective‐tissue tumors that can arise in any anatomic location; they can be asymptomatic, or they can result in pain, deformity, swelling, and loss of mobility and/or threaten visceral organs with bowel perforation, hydronephrosis, neurovascular damage, and other complications. Existing clinical trial endpoints such as the Response Evaluation Criteria in Solid Tumors (version 1.1) and progression‐free survival are inadequate in capturing treatment efficacy. This study was designed to develop a novel clinical trial endpoint by capturing patient‐reported outcomes (PROs).

Methods

Following best practices in qualitative methodology, this study used concept elicitation (CE) interviews to explore desmoid patients' perspectives on key disease‐related symptoms and impacts. Qualitative analysis was performed to determine the relative frequency and disturbance of symptoms and impacts as well as other characteristics of these concepts. A draft PRO scale was then developed and tested with cognitive interviewing. Information from the interviews was subsequently incorporated into the refined PRO scale.

Results

CE interviews with desmoid patients (n = 31) helped to identify salient concepts and led to a draft scale that included symptom and impact scales. Cognitive interviews were completed with additional patients (n = 15) across 3 phases. Patient input was used to refine instructions, revise and/or remove items, and modify the response scale. This resulted in an 11‐item symptom scale and a 17‐item impact scale.

Conclusions

This is the first disease‐specific PRO instrument developed for desmoid tumors. The instrument is available as an exploratory endpoint in clinical trials. This study highlights the feasibility and challenges of developing PRO instruments for rare diseases.
Finite element comparison of the effect of absorbers' design in the surrounding bone of dental implants
Authors: Ashrafi Mehran , Ghalichi Farzan , Mirzakouchaki Behnam , Arruga Alberto , Doblare Manuel
Published: November 2019

Despite the high success rate achieved in current dental implantation, there are still important problems to solve like incomplete early osteointegration, bone damage, and long‐term implant loosening. Highly compliant stress absorbers are a possible solution to these problems. Although several works examined the stress‐strain distribution in bone without and with absorbers to show their favorable results, none of them analyzed their impact on long‐term remodeling.

Here, we analyze this effect by comparing the evolution of stress and bone mass density without and with different designs of absorbers with those of the healthy tooth. Several finite element models with ABAQUS, corresponding to each design considered, were built to obtain the mechanical conditions in bone and implant. Then a mechanobiological bone remodeling model that considers damage accumulation and its repair during the remodeling process was used to compute the bone density redistribution. This approach allows assessing both the short‐term density loss and the relative micromovement between bone and implant.

We analyze the stress distributions in both bone and implant as well as the relative micromovement of the implant. We also present the evolution of damage and bone volume fraction. These results show that the addition of absorbers can reduce the stress in the bone around the implant. The obtained results also show that using stress absorbers reduces damage in bone, while increasing the number of absorbers does not necessarily improves damage reduction. We conclude that using implants with a correct design of absorbers prevents damage and stress shielding, reducing implant loosening.
Modular Design of Stimuli‐Responsive Supramolecular Nanocarriers Based on Pro‐Guest Strategy
Authors: Mao Weipeng , Yang Xuan , Ma Da
Published: November 2019

High affinity host‐guest interactions were used to assemble supramolecular nanocarriers, and controlled release cargo based on a “pro‐guest” strategy. Supramolecular nanocarriers were prepared by modular design, which were responsive to photo‐irradiation or reducing agents. Model cargo nile red was stably encapsulated by nanocarriers in water, and released when photo‐irradiation or reducing agent was applied. Cargo release rate was tunable by using different pro‐guests for photo‐responsive nanocarriers. A mechanistic study was carried out to confirm a cascade process of stimuli‐responsive pro‐guest degradation and competitive displacement. Supramolecular nanocarriers were able to deliver model cargo to the cell cytoplasm.
A harmony‐based approach to generating sequential color schemes for maps
Authors: Chen Taisheng , Zhu A‐Xing , Wu Mingguang , Chen Menglin , Zhang Mingda , Jiang Weixing , Lu Yue , Wang Hong
Published: November 2019

Generating high‐quality sequential color schemes for maps is challenging for most mapmakers. This article presents a harmony‐based approach for automatically generating sequential color schemes for maps. The proposed approach consists of two steps: (a) color harmony quantification for sequential color schemes on maps and (b) color scheme generation using quantified color harmony factors. The approach was tested using three experimental maps, including the Chinese water body density index map, Chinese vegetation cover index map, and Chinese population density map. Effectiveness was evaluated by comparing color schemes generated by the proposed approach with those created by the probability‐based method and ColorBrewer. Twenty‐six participants were invited to rate each map color scheme using a 5‐point scale. A t test was also used to examine the significance of the difference. The results show that the mean points of color schemes using the proposed approach are higher than those using the probability‐based method, and the corresponding P‐values are far lower than .05, which suggests that the proposed approach is better than the probability‐based method and can improve the sequential color scheme quality in automatic ways. The mean points of color schemes created using the proposed approach are also slightly higher than or similar to those of ColorBrewer, which are well‐known map color schemes manually designed by an experienced cartographer. This result further suggests that the proposed approach can meet the requirement of automatic generation for high‐quality sequential color schemes on maps.
Coupling Rhodium‐Catalyzed Hydroformylation of 10‐Undecenitrile with Organic Solvent Nanofiltration: Toluene Solution versus Solvent‐Free Processes
Authors: Lejeune Antoine , Le Goanvic Lucas , Renouard Thierry , Couturier Jean‐Luc , Dubois Jean‐Luc , Carpentier Jean‐François , Rabiller‐Baudry Murielle
Published: November 2019

Intensification of the rhodium‐catalyzed hydroformylation process to produce 12‐oxo‐dodecanenitrile from biosourced 10‐undecenitrile was performed by coupling the reaction with organic solvent nanofiltration (OSN) for the recycling of the expensive Rh catalyst and the ligands. Four phosphorus‐based ligands were compared with respect to their catalytic performance and rejection in OSN. Biphephos showed the best compromise and up to 3 reaction‐OSN cycles were performed in toluene. A good recycling of the catalytic system was evidenced arising from the OSN (up to 88 % rejection). In order to develop a greener process, a similar approach was achieved in bulk (i. e. solvent‐free medium), thus proving the catalyst recycling feasibility but also that the optimal OSN conditions are not the same as for toluene. Finally, integration of OSN in the overall production process is discussed, aiming at the proposal of a hybrid separation process involving a combination of OSN and distillation for an energy‐efficient separation step.
Pooled CRISPR Screens in Drosophila Cells
Authors: Viswanatha Raghuvir , Brathwaite Roderick , Hu Yanhui , Li Zhongchi , Rodiger Jonathan , Merckaert Pierre , Chung Verena , Mohr Stephanie E. , Perrimon Norbert
Published: November 2019

High‐throughput screens in Drosophila melanogaster cell lines have led to discovery of conserved gene functions related to signal transduction, host‐pathogen interactions, ion transport, and more. CRISPR/Cas9 technology has opened the door to new types of large‐scale cell‐based screens. Whereas array‐format screens require liquid handling automation and assay miniaturization, pooled‐format screens, in which reagents are introduced at random and in bulk, can be done in a standard lab setting. We provide a detailed protocol for conducting and evaluating genome‐wide CRISPR single guide RNA (sgRNA) pooled screens in Drosophila S2R+ cultured cells. Specifically, we provide step‐by‐step instructions for library design and production, optimization of cytotoxin‐based selection assays, genome‐scale screening, and data analysis. This type of project takes ∼3 months to complete. Results can be used in follow‐up studies performed in vivo in Drosophila, mammalian cells, and/or other systems. © 2019 by John Wiley & Sons, Inc.

Basic Protocol: Pooled‐format screening with Cas9‐expressing Drosophila S2R+ cells in the presence of cytotoxin

Support Protocol 1: Optimization of cytotoxin concentration for Drosophila cell screening

Support Protocol 2: CRISPR sgRNA library design and production for Drosophila cell screening

Support Protocol 3: Barcode deconvolution and analysis of screening data
Clinical psychologists' use of transformative models of psychosis
Authors: Cooke Anne , Brett Caroline
Published: November 2019

Some theories (e.g. Jackson's Paradigm Shifting Hypothesis) and many personal accounts suggest that some psychotic crises, whilst distressing, can also be transformative, leading to growth and valued outcomes. However, little is known about the extent to which this idea informs mainstream mental health care. Clinical psychologists are influential advocates of psychosocial approaches more broadly: This study explored their use of transformative models. Twelve U.K. clinical psychologists were interviewed: Transcripts informed a grounded theory. No participants saw psychosis as a purely biological problem where the content of experiences is irrelevant. Two held a “biopsychosocial” model, viewing psychosis as an illness with psychosocial elements. Most either held a continuum view (i.e., schizotypy), in which psychosis proneness was also associated with positive attributes such as creativity or sensitivity, or a “fully psychological” view, seeing experiences as meaningful and/or as adaptive responses to events. Many believed that psychosis can be transformative in a broad sense, that is, lead to “post‐traumatic growth.” Some went further, believing that it can be a purposeful (e.g., an attempt, albeit painful and sometimes unsuccessful, to solve problems) or even a spiritual phenomenon. Participants' perspectives influenced their therapeutic approach: Those who saw experiences as purposeful were more likely to facilitate direct engagement with them and to support clients to explore potentially transformative aspects. However, this represented an extension of conventional approaches rather than being qualitatively different. More research is needed to clarify how widespread this approach is, to explore its utility, and to establish for whom and when it may be appropriate.
Idiopathic and immune‐related pulmonary fibrosis: diagnostic and therapeutic challenges
Authors: McLean‐Tooke Andrew , Moore Irene , Lake Fiona
Published: November 2019

Interstitial lung disease (ILD) encompasses a large group of pulmonary conditions sharing common clinical, radiological and histopathological features as a consequence of fibrosis of the lung interstitium. The majority of ILDs are idiopathic in nature with possible genetic predisposition, but is also well recognised as a complication of connective tissue disease or with certain environmental, occupational or drug exposures. In recent years, a concerted international effort has been made to standardise the diagnostic criteria in ILD subtypes, formalise multidisciplinary pathways and standardise treatment recommendations. In this review, we discuss some of the current challenges around ILD diagnostics, the role of serological testing, especially, in light of the new classification of Interstitial Pneumonia with Autoimmune Features (IPAF) and discuss the evidence for therapies targeted at idiopathic and immune‐related pulmonary fibrosis.
Rapid sequencing‐based diagnosis of infectious bacterial species from meningitis patients in Zambia
Authors: Nakagawa So , Inoue Shigeaki , Kryukov Kirill , Yamagishi Junya , Ohno Ayumu , Hayashida Kyoko , Nakazwe Ruth , Kalumbi Mox , Mwenya Darlington , Asami Nana , Sugimoto Chihiro , Mutengo Mable M , Imanishi Tadashi
Published: November 2019

Objectives

We have developed a portable system for the rapid determination of bacterial composition for the diagnosis of infectious diseases. Our system comprises of a nanopore technology‐based sequencer, MinION, and two laptop computers. To examine the accuracy and time efficiency of our system, we provided a proof‐of‐concept for the detection of the causative bacteria of 11 meningitis patients in Zambia.

Methods

We extracted DNA from cerebrospinal fluid samples of each patient and amplified the 16S rRNA gene regions. The sequencing library was prepared, and the sequenced reads were simultaneously processed for bacterial composition determination using the minimap2 software and the representative prokaryote genomes.

Results

The sequencing results of four of the six culture‐positive samples were consistent with those of conventional culture‐based methods. The dominant bacterial species in each of these samples were identified from the sequencing data within only 3 min. Although the major bacterial species were also detected from the other two culture‐positive samples and five culture‐negative samples, their presence could not be confirmed. Moreover, as a whole, although the number of sequencing reads obtained within a short sequencing run was small, there was no change in the major bacterial species over time with prolonged sequencing. In addition, the processing time strongly correlated with the number of sequencing reads used for the analysis.

Conclusion

Our results suggest that time‐effective analysis could be achieved by determining the number of sequencing reads required for the rapid diagnosis of infectious bacterial species depending on the complexity of bacterial species in a sample.
Machine Learning of Discriminative Gate Locations for Clinical Diagnosis
Authors: Ji Disi , Putzel Preston , Qian Yu , Chang Ivan , Mandava Aishwarya , Scheuermann Richard H. , Bui Jack D. , Wang Huan‐You , Smyth Padhraic
Published: November 2019

High‐throughput single‐cell cytometry technologies have significantly improved our understanding of cellular phenotypes to support translational research and the clinical diagnosis of hematological and immunological diseases. However, subjective and ad hoc manual gating analysis does not adequately handle the increasing volume and heterogeneity of cytometry data for optimal diagnosis. Prior work has shown that machine learning can be applied to classify cytometry samples effectively. However, many of the machine learning classification results are either difficult to interpret without using characteristics of cell populations to make the classification, or suboptimal due to the use of inaccurate cell population characteristics derived from gating boundaries. To date, little has been done to optimize both the gating boundaries and the diagnostic accuracy simultaneously. In this work, we describe a fully discriminative machine learning approach that can simultaneously learn feature representations (e.g., combinations of coordinates of gating boundaries) and classifier parameters for optimizing clinical diagnosis from cytometry measurements. The approach starts from an initial gating position and then refines the position of the gating boundaries by gradient descent until a set of globally‐optimized gates across different samples are achieved. The learning procedure is constrained by regularization terms encoding domain knowledge that encourage the algorithm to seek interpretable results. We evaluate the proposed approach using both simulated and real data, producing classification results on par with those generated via human expertise, in terms of both the positions of the gating boundaries and the diagnostic accuracy. © 2019 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.
Challenges in the Multivariate Analysis of Mass Cytometry Data: The Effect of Randomization
Authors: Papoutsoglou Georgios , Lagani Vincenzo , Schmidt Angelika , Tsirlis Konstantinos , Cabrero David‐Gómez , Tegnér Jesper , Tsamardinos Ioannis
Published: November 2019

Cytometry by time‐of‐flight (CyTOF) has emerged as a high‐throughput single cell technology able to provide large samples of protein readouts. Already, there exists a large pool of advanced high‐dimensional analysis algorithms that explore the observed heterogeneous distributions making intriguing biological inferences. A fact largely overlooked by these methods, however, is the effect of the established data preprocessing pipeline to the distributions of the measured quantities. In this article, we focus on randomization, a transformation used for improving data visualization, which can negatively affect multivariate data analysis methods such as dimensionality reduction, clustering, and network reconstruction algorithms. Our results indicate that randomization should be used only for visualization purposes, but not in conjunction with high‐dimensional analytical tools. © 2019 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.
Energy efficient distributed lightweight authentication and encryption technique for IoT security
Authors: Sudhakaran Pradeep , C Malathy
Published: November 2019

Internet of Things (IoT) is an intelligent technology and service that mutually communicates information between human and devices or between Internet‐based devices. In IoT security, the authentication should be distributed and lightweight. Token generation should be based on the trust worthiness of the devices, and it needs to ensure fast authentication and authorization. In this paper, we propose an Energy Efficient Distributed Lightweight Authentication and Encryption (EEDLAE) technique for IoT security. In our proposed technique, the receiver generates the token for each sender. The token expiration time is determined based on the trust value of each sender, and sleep period of the receiver radio is determined based on its remaining energy. For encryption, Counter with Cipher Block Chaining‐Message Authentication Code (CCM) is applied. Experimental results show that EEDLAE technique can hold out against affected packets, higher resilience against node capture, increased throughput, and residual energy, compared with the existing technique.
A simple method to immunopurify erythropoiesis stimulating agents from urine, aiming to optimize erythropoietin screening by SAR‐PAGE
Authors: Heiland Carmel E. , Masquelier Michèle , Bhuiyan Hasanuzzaman , Ericsson Magnus
Published: November 2019

The efficiency of the immunopurification step of urinary erythropoietin (EPO) and recombinant forms is important for their optimal detection in antidoping screening. Previous investigations of immunopurification techniques have been done for immunomagnetic beads, EPO Purification Kit (EPK) columns (MAIIA Diagnostics), and enzyme‐linked immunosorbent assay (ELISA) microplates (Stemcell Technologies) conjugated/coated with anti‐EPO antibodies. In this study, a new immunopurification technique using anti‐EPO sepharose gel beads, developed by MAIIA Diagnostics, to simplify and minimize sample handling was evaluated. This EPO Purification Gel Kit (EPGK) was compared with our current routine EPK for limit of detection (LOD). Linearity, recovery, repeatability, sample incubation time, and sample volume were also evaluated for EPGK. The LODs and linearity for EPK and EPGK were comparable to each other and the recovery for BRP, NESP, CERA, and EPO‐Fc were within the range of other studies, and concentration of the sample eluate improved the recovery results. Little variation was seen within days, between days, and between operators. A 90 minute incubation of the sample with the sepharose gel beads is sufficient for most of the erythropoiesis stimulating agents (ESAs) tested, with 10 mL being an optimal sample volume for EPGK. The improved sample handling, higher sample throughput and the reduced working time demonstrate that the EPGK is a better alternative to the current MAIIA EPK immunopurification method for urine. The EPO Purification Gel Kit (from MAIIA Diagnostics) was evaluated and validated for immunopurification of endogenous erythropoietin and exogenous erythropoiesis stimulating agents from urine samples. The kit was a better alternative to that currently used (EPO Purification Kit) in many antidoping laboratories because it improves sample handling and increases sample throughput.
The Photoinduced Metal‐Free Hydrotrifluoromethylation of Vinyl Phosphonates or Phosphine Oxides
Authors: Yao Qiuli , Ren Linjing , Xiang Dan , Li Kexin , Yan Boyu , Ran Maogang , He Jiaxin , Zhao Liang
Published: November 2019

We describe a simple and metal‐free photochemical strategy for the direct hydrotrifluoromethylation of vinyl phosphonates or phosphine oxides by sodium triflinate under ultraviolet or visible light irradiation. Acetone and diacetyl were used as radical initiators to generate CF3 radicals that were efficiently added to vinyl phosphonates or phosphine oxide to yield β‐trifluoromethylated phosphorus compounds without the use of any catalyst. A broad scope of substrates scope is demonstrated in moderate to excellent yields. Mechanistic experiments were performed to study the source of hydrogen; the results indicate that H2O in the solvent or additive is the primary hydrogen source.
The Need for Inclusion: The relationships between Relational and Collective inclusion needs and psychological well‐and ill‐being
Authors: Valcke Barbara , Van Hiel Alain , Van Assche Jasper , Van Roey Thomas , Onraet Emma , Roets Arne
Published: November 2019

The Need to Belong concept encompasses the need for inclusion and the discomfort with exclusion. The Need to Belong Scale of Leary, Kelly, Cottrell, and Schreindorfer (2013, p. 610), however, primarily probes into the discomfort aspect, and it does not distinguish between relational and collective self‐levels. Two studies (total N = 429) provided evidence of the reliability, distinctiveness, and validity of the newly developed Need for Inclusion scale. The results revealed that Relational Need for Inclusion positively contributes to psychological well‐being and negatively to ill‐being. Collective Need for Inclusion was distinctively related to collective and group‐level outcomes of self, such as social trust and collective self‐esteem. Need to Belong yielded a reversed pattern of results for the studied outcomes. It is concluded that inclusion needs and discomfort with exclusion are positively related but clearly distinct, and that future studies should investigate their joint effects in a single research design.
Assessing the Efficacy of a Sediment Remediation Program Using Benthic and Pelagic Copepod Bioassays
Authors: Charry Maria P. , Keesing Vaughan , Gaw Sally , Costello Mark J. , Champeau Olivier , Tremblay Louis A.
Published: November 2019

Tributyltin is an organotin chemical that has been commonly used in ship antifouling paints. Despite the global total prohibition of tributyltin-based paint in 2008, tributyltin continues to be found at toxic levels in areas of high maritime traffic such as ports and harbors. A remediation program was conducted at a New Zealand port to reduce tributyltin and copper concentrations to acceptable values. The present study assessed the efficacy of the program using a combination of chemical analyses and copepod bioassays. Sediment and water samples were collected at 3 locations along a spatial gradient within the port, and concentrations of various organotin compounds and trace metal levels were measured pre- and postremediation. The toxicity of sediment and elutriate samples was estimated by benthic and pelagic copepod bioassays. Although acute toxicity in sediment samples was reduced following remediation, reproductive success was still affected for the benthic copepod. This approach combining chemical analysis and bioassays is promising for assessing the efficacy of remediation processes at contaminated marine sites. Environ Toxicol Chem 2020;39:492–499. © 2019 SETAC

Abstract

The remediation of port sediment reduced tributyltin levels and toxicity, but the remediated sediment remained chronically toxic to a benthic copepod.
Do monetary policy transparency and central bank communication reduce interest rate disagreement?
Authors: Seelajaroen Ruttachai , Budsaratragoon Pornanong , Jitmaneeroj Boonlert
Published: November 2019

Yes. This study produces evidence that monetary policy transparency and communication policy of the Bank of England have information content in reducing disagreement about interest rate forecasts. Different from most extant studies employing the transparency index derived from official documents of the central banks, this study extends the literature by using a recently developed market‐based monetary transparency index. Moreover, this study analyzes forecast disagreement in a multivariate perspective based on survey data of short‐ and long‐term rates over short and long horizons. This study characterizes several patterns on forecast disagreement related to maturities of interest rates, forecast horizons, recessions, forward guidance, credibility, transparency, and communication policy. Interestingly, disagreement among the Monetary Policy Committee in policy rate decisions is associated with lower disagreement among professional forecasters on interest rate outlook, whereas neither announcement of changes in policy rates nor publication of inflation reports affects forecast disagreement. These results have important implications for monetary policymakers in managing market expectations of interest rates.