bluuebunny/crossref_metadata_2025_split huggingface dataset:
Marco Iansiti and Karim Lakhani: strategies for the new breed of “AI first” organizations
Authors: Leavy Brian 
Published: March 2020

Purpose
This interview introduces the concept of the “AI first company”, a new breed of organization that is transforming the economy and defining the emergence of a new age.

Design/methodology/approach
An interview with Harvard digital strategy experts, Marco Iansiti and Karim Lakhani, about their new book, Competing in the Age of AI: Strategy and Leadership When Algorithms and Networks Run the World. Marco Iansiti is the David Sarnoff Professor of Business Administration at Harvard Business School (HBS) and heads the school’s Technology and Operations Management Unit and the Digital Initiative. Karim R. Lakhani is the Charles E. Wilson Professor of Business Administration at HBS, and the founder and co-director of the Laboratory for Innovation Science and co-founder of the Digital Initiative at Harvard. 10; 10;The authors were interviewed by Brian Leavy, emeritus professor of strategy at Dublin City University Business School and a Strategy & Leadership contributing editor.

Findings
Digital transformation is not about creating a digital function or spinning off a digital unit, it’s about fundamentally restructuring the core of the firm by building a data-centric operating architecture supported by an agile organization that enables on-going change.

Practical implications
Essentially, we are moving away from an era of core competencies that differ from industry to industry to an age shaped by data and analytics and powered by algorithms. The concept of network is superceding the concept of industry in defining strategic options for firms.

Originality/value
The emergence of the “Age of AI” has possibly created the greatest entrepreneurial opportunity in the history of civilization and the world is literally jammed with entrepreneurial activity. Marco Iansiti and Karim Lakhani suggest ways to maximize that opportunity.
Effect of different thermocouple constructions on heat-level vapour phase soldering profiles
Authors: Alaya Mohamed Amine , Megyeri Viktória , Bušek David , Harsányi Gábor , Geczy Attila 
Published: March 2020

Purpose
To improve productivity and reach better quality in assembling, measurements and proper process controlling are a necessary factor. This study aims to focus on the monitoring heat-level-based vapour phase reflow soldering (VPS), where – as it was found – different thermocouple constructions can affect the set parameters of the oven and resulting soldering profiles significantly.

Design/methodology/approach
The study experiments showed significant alteration of the heating profiles during the process of the reflowing using different construction of k-type thermocouples. In a heat-level-based VPS oven, polytetrafluoroethylene (PTFE), perfluoroalkoxy (PFA) gas and water-resistant, fibreglass, thin PFA and ultrathin PFA-covered thermocouples were tested with ±1 °C precision. The oven parameters were swept according to the heating power; the length of the introduced thermocouple cables was also taken into account. An FR4-based sample PCB was used for monitoring the temperature.

Findings
According to the results, due to the mass and volume of the thermocouples’ wires, different transients were observed on the resulting soldering profiles on the same sample PCB. The thermocouples with lower thermal mass result in faster profiles and significantly different heating factor values compared to the thermocouples that have larger thermal mass. Consequently, the length of the thermocouple wires put in the oven has also considerable effect on the heat transfer of the PCB inside the oven as well.

Originality/value
The paper shows that the thermocouple construction must be taken into account when setting up a required soldering profile, while the thermal mass of the wires might cause a significant difference in the prediction of the actual and expected soldering temperatures.
Meritocracy, Elitism and Inequality
Authors: Mijs Jonathan J.B. , Savage Mike 
Published: March 2020

AbstractThe appeal of meritocracy is plain to see, because it appears to promote equality of opportunity. However, in this paper we argue that meritocracy is also a deeply elitist project. Firstly, we place Michael Young in context to show how his critique of meritocracy should be understood as a socialist vision to ameliorate class divides. Secondly, we show how economic inequality in the UK has not generated systematic resistance: in fact, inequality and belief in meritocracy have gone hand in hand. Thirdly, we argue that people see their own lives as meritocratic rather than ascribed, and that such values are deeply embedded in popular life. We offer two explanations for how such views have come about, and show how they have helped construct a more unequal society.
DMHF (2,5‐dimethyl‐4‐hydroxy‐3(2H)‐furanone), a volatile food component generated by the Maillard reaction, promotes appetite and changes gene expression in the rat brain through inhalation
Authors: Yokoyama Issei , Nakai Yuji , Suzuki Yoshihiro , Ohata Motoko , Komiya Yusuke , Nagasao Jun , Arihara Keizo 
Published: March 2020

AbstractInhalation of odors can affect physiological parameter and change gene expression‐related specific function. 2,5‐Dimethyl‐4‐hydroxy‐3(2H)‐furanone (DMHF) is one of the major odor compounds generated by the Maillard reaction. We previously reported that the inhalation of DMHF decreased systolic blood pressure via the autonomic nervous system in rats. The autonomic nervous system is also closely related to appetite regulation. The present study investigated the effects of DMHF on dietary intake and gene expression. The inhalation of DMHF increased the dietary intake of rats during the feeding period. However, body weight did not change after 6 weeks feeding. A DNA microarray analysis showed that DMHF altered gene expression associated with feeding behavior and neurotransmission in the rat brain. DMHF inhalation promotes appetite and changes gene expression in rats. Furthermore, phenotypic changes may regulate neurotransmission and appetite at the mRNA level in addition to controlling the autonomic nervous system.Practical ApplicationDMHF is an important flavor component in the food industry. In this study, we first observed that the inhalation of DMHF promotes appetite. This finding is directly connected with the industrial application.
Galacto‐conjugation of Navitoclax as an efficient strategy to increase senolytic specificity and reduce platelet toxicity
Authors: González‐Gualda Estela , Pàez‐Ribes Marta , Lozano‐Torres Beatriz , Macias David , Wilson Joseph R. , González‐López Cristina , Ou Hui‐Ling , Mirón‐Barroso Sofía , Zhang Zhenguang , Lérida‐Viso Araceli , Blandez Juan F. , Bernardos Andrea , Sancenón Félix , Rovira Miguel , Fruk Ljiljana , Martins Carla P. , Serrano Manuel , Doherty Gary J. , Martínez‐Máñez Ramón , Muñoz‐Espín Daniel 
Published: March 2020

AbstractPharmacologically active compounds with preferential cytotoxic activity for senescent cells, known as senolytics, can ameliorate or even revert pathological manifestations of senescence in numerous preclinical mouse disease models, including cancer models. However, translation of senolytic therapies to human disease is hampered by their suboptimal specificity for senescent cells and important toxicities that narrow their therapeutic windows. We have previously shown that the high levels of senescence‐associated lysosomal β‐galactosidase (SA‐β‐gal) found within senescent cells can be exploited to specifically release tracers and cytotoxic cargoes from galactose‐encapsulated nanoparticles within these cells. Here, we show that galacto‐conjugation of the BCL‐2 family inhibitor Navitoclax results in a potent senolytic prodrug (Nav‐Gal), that can be preferentially activated by SA‐β‐gal activity in a wide range of cell types. Nav‐Gal selectively induces senescent cell apoptosis and has a higher senolytic index than Navitoclax (through reduced activation in nonsenescent cells). Nav‐Gal enhances the cytotoxicity of standard senescence‐inducing chemotherapy (cisplatin) in human A549 lung cancer cells. Concomitant treatment with cisplatin and Nav‐Gal in vivo results in the eradication of senescent lung cancer cells and significantly reduces tumour growth. Importantly, galacto‐conjugation reduces Navitoclax‐induced platelet apoptosis in human and murine blood samples treated ex vivo, and thrombocytopenia at therapeutically effective concentrations in murine lung cancer models. Taken together, we provide a potentially versatile strategy for generating effective senolytic prodrugs with reduced toxicities.
Measurement concerns and agreement of environmental social governance ratings
Authors: Widyawati Luluk 
Published: March 2020

AbstractMeasurement quality of environmental, social, and governance (ESG) rating is important, considering the increasing interest in socially responsible investment. This paper examines the measurement quality of four ESG ratings. Comprehensive analysis of the ratings, including its dimensionality, reliability, and validity suggests that they have significantly different measurement construct and measurement concerns, despite some commonalities. This study also presents a novel approach to examine the convergence of ESG ratings by assessing the level of agreement. The results of interrater reliability analysis suggest that while the agreement between ESG scores is low, there is evidence of a low to moderate agreement of ESG rankings.
A life‐time of hazardous drinking and harm to health among older adults: findings from the Whitehall II prospective cohort study
Authors: Ng Fat Linda , Bell Steven , Britton Annie 
Published: March 2020

AbstractAimsTo investigate associations of life‐time hazardous and binge drinking with biomarkers of cardiometabolic health, liver function, cardiovascular disease (CVD) and mortality.DesignProspective cohort study with median follow‐up time to CVD incidence of 4.5 years.SettingLondon, UK: civil servants within the Whitehall II Study.ParticipantsA total of 4820 drinkers aged 59–83 years with biological measurements during the 2011–12 survey.MeasurementsHazardous drinking was defined as having an AUDIT‐C score ≥ 5 calculated at each decade of life, forming the following groups: never hazardous drinker, former early (stopping before age 50), former later (stopping after age 50), current hazardous drinker and consistent hazardous drinker (hazardous drinker at each decade of life).FindingsMore than half the sample had been hazardous drinkers at some point during their life‐time, comprising former early (< age 50) (19%), former later (≥ age 50) (11%), current (21%) and consistent hazardous drinker (AUDIT‐C ≥ 5 across life (5%). After adjusting for covariates, waist circumference was larger with more persistent hazardous drinking (e.g. compared with never hazardous drinkers, former early had increased waist circumference by 1.17 cm [95% confidence interval (CI) = 0.25‐2.08]; former later by 1.88 cm (CI = 0.77–2.98); current by 2.44 cm (CI = 1.50–3.34) and consistent hazardous drinker by 3.85 cm (CI = 2.23–5.47). Current hazardous drinkers had higher systolic blood pressure (2.44 mmHg, CI = 1.19–3.68) and fatty liver index scores (4.05 mmHg, CI = 2.92–5.18) than never hazardous drinkers. Current hazardous drinkers [hazard ratio (HR) = 2.75, CI = 1.44–5.22) had an elevated risk of stroke, and former later hazardous drinkers had an elevated risk of non‐CVD mortality (HR = 1.93, CI = 1.19–3.14) than never hazardous drinkers. Life‐time binge drinking was associated with larger waist circumferences and poorer liver function compared with never binge drinkers.ConclusionHazardous drinking may increase cardiometabolic risk factors; this is made worse by persistent hazardous drinking throughout life, particularly in relation to weight gain, suggesting benefits of early intervention.
Outcomes of older patients with primary central nervous system lymphoma treated in routine clinical practice in the UK: methotrexate dose intensity correlates with response and survival
Authors: Martinez‐Calle Nicolás , Poynton Edward , Alchawaf Alia , Kassam Shireen , Horan Matthew , Rafferty Mark , Kelsey Phillipa , Scott Gemma , Culligan Dominic J. , Buckley Hannah , Lim Yeong J. , Ngu Loretta , McCulloch Rory , Rowntree Clare , Wright Josh , McKay Pamela , Fourali Samih , Eyre Toby A. , Smith Jeffrey , Osborne Wendy , Yallop Deborah , Linton Kim , Fox Christopher P. , Cwynarski Kate 
Published: March 2020

SummaryData on older patients with primary central nervous system lymphoma (PCNSL) are scarce. Comorbidities and performance status frequently compromise outcomes in this group. Medical records for consecutive patients ≥65 years (n = 244) with PCNSL diagnosed 2012–2017 from 14 UK centres were retrospectively reviewed. Of these 192 patients received methotrexate (MTX)‐based treatment. Patients were categorised based on clinician's treatment choice into ‘palliative’ (n = 52), ‘less intensive: MTX ± rituximab ± alkylators’ (n = 74) and ‘intensive: MTX/cytarabine combinations’ (n = 118) groups. Complete remission (CR) rate, two‐year progression‐free survival (PFS) and overall survival (OS) rates were 49%, 11% and 24% for the less intensive and 69%, 40% and 50% for the intensive groups. Treatment‐related mortality (TRM) was 6·8% for MTX‐treated patients. Median MTX cumulative dose was 8·8 g/m2 (range 1·5–21) over a median of three cycles. Higher relative dose intensity of MTX (MTX‐RDI) was associated with improved PFS and OS in both groups adjusting for age, Eastern cooperative oncology group (ECOG) score and baseline parameters. Two‐year PFS and OS for patients receiving four or more induction cycles followed by consolidation (n = 36) were 65% and 70% respectively. Older patients completing MTX‐based induction and consolidation had clinical outcomes similar to those in younger cohorts. These retrospective data suggest that maximising MTX‐RDI and delivering consolidation in a subgroup of older patients may improve clinical outcomes.
FNDC3B 3′‐UTR shortening escapes from microRNA‐mediated gene repression and promotes nasopharyngeal carcinoma progression
Authors: Li Ying‐Qing , Chen Yang , Xu Ya‐Fei , He Qing‐Mei , Yang Xiao‐Jing , Li Ying‐Qin , Hong Xiao‐Hong , Huang Sheng‐Yan , Tang Ling‐Long , Liu Na 
Published: March 2020

AbstractAlternative polyadenylation (APA), which induces shortening of the 3′‐UTR, is emerging as an important feature in cancer development and progression. Nevertheless, the effects and mechanisms of APA‐induced 3′‐UTR shortening in nasopharyngeal carcinoma (NPC) remain largely unclear. Fibronectin type III domain containing 3B (FNDC3B) tended to use proximal polyadenylation site and produce shorter 3′‐UTR according to our previous sequencing study. Herein, we found that FNDC3B with shorter 3′‐UTR could escape from miRNA‐mediated gene repression, and caused its increased expression in NPC. Knocking down of FNDC3B inhibited NPC cell proliferation, migration, invasion, and metastasis in vitro and in vivo. Overexpression of FNDC3B, especially those with shorter 3′‐UTR, promoted NPC progression. Furthermore, the mechanism study revealed that FNDC3B could bind to and stabilize myosin heavy chain 9 (MYH9) to activate the Wnt/β‐catenin signaling pathway. In addition, MYH9 could reverse the inhibitory effects of FNDC3B knockdown in NPC. Altogether, our results suggested that the 3′‐UTR shortening of FNDC3B mRNA mediated its overexpression in NPC and promoted NPC progression by targeting MYH9. This newly identified FNDC3B‐MYH9‐Wnt/β‐catenin axis could represent potential targets for individualized treatment in NPC.
Potential new therapy of Rapalink‐1, a new generation mammalian target of rapamycin inhibitor, against sunitinib‐resistant renal cell carcinoma
Authors: Kuroshima Kazuki , Yoshino Hirofumi , Okamura Shunsuke , Tsuruda Masafumi , Osako Yoichi , Sakaguchi Takashi , Sugita Satoshi , Tatarano Shuichi , Nakagawa Masayuki , Enokida Hideki 
Published: March 2020

AbstractSunitinib, a multitargeted receptor tyrosine kinase inhibitor including vascular endothelial growth factor, has been widely used as a first‐line treatment against metastatic renal cell carcinoma (mRCC). However, mRCC often acquires resistance to sunitinib, rendering it difficult to treat with this agent. Recently, Rapalink‐1, a drug that links rapamycin and the mTOR kinase inhibitor MLN0128, has been developed with excellent therapeutic effects against breast cancer cells carrying mTOR resistance mutations. The aim of the present study was to evaluate the in vitro and in vivo therapeutic efficacy of Rapalink‐1 against renal cell carcinoma (RCC) compared to temsirolimus, which is commonly used as a small molecule inhibitor of mTOR and is a derivative of rapamycin. In comparison with temsirolimus, Rapalink‐1 showed significantly greater effects against proliferation, migration, invasion and cFolony formation in sunitinib‐naïve RCC cells. Inhibition was achieved through suppression of the phosphorylation of substrates in the mTOR signal pathway, such as p70S6K, eukaryotic translation initiation factor 4E‐binding protein 1 (4EBP1) and AKT. In addition, Rapalink‐1 had greater tumor suppressive effects than temsirolimus against the sunitinib‐resistant 786‐o cell line (SU‐R 786‐o), which we had previously established, as well as 3 additional SU‐R cell lines established here. RNA sequencing showed that Rapalink‐1 suppressed not only the mTOR signaling pathway but also a part of the MAPK signaling pathway, the ErbB signaling pathway and ABC transporters that were associated with resistance to several drugs. Our study suggests the possibility of a new treatment option for patients with RCC that is either sunitinib‐sensitive or sunitinib‐resistant.
Reprograming the tumor immunologic microenvironment using neoadjuvant chemotherapy in osteosarcoma
Authors: Deng Chuangzhong , Xu Yanyang , Fu Jianchang , Zhu Xiaojun , Chen Hongmin , Xu Huaiyuan , Wang Gaoyuan , Song Yijiang , Song Guohui , Lu Jinchang , Liu Ranyi , Tang Qinglian , Huang Wenlin , Wang Jin 
Published: March 2020

AbstractTumor‐infiltrating immune cells play a crucial role in tumor progression and response to treatment. However, the limited studies on infiltrating immune cells have shown inconsistent and even controversial results for osteosarcoma (OS). In addition, the dynamic changes of infiltrating immune cells after neoadjuvant chemotherapy are largely unknown. We downloaded the RNA expression matrix and clinical information of 80 OS patients from the TARGET database. CIBERSORT was used to evaluate the proportion of 22 immune cell types in patients based on gene expression data. M2 macrophages were found to be the most abundant immune cell type and were associated with improved survival in OS. Another cohort of pretreated OS samples was evaluated by immunohistochemistry to validate the results from CIBERSORT analysis. Matched biopsy and surgical samples from 27 patients were collected to investigate the dynamic change of immune cells and factors before and after neoadjuvant chemotherapy. Neoadjuvant chemotherapy was associated with increased densities of CD3+ T cells, CD8+ T cells, Ki67 + CD8+ T cells and PD‐L1+ immune cells. Moreover, HLA‐DR‐CD33+ myeloid‐derived suppressive cells (MDSC) were decreased after treatment. We determined that the application of chemotherapy may activate the local immune status and convert OS into an immune “hot” tumor. These findings provide rationale for investigating the schedule of immunotherapy treatment in OS patients in future clinical trials.
Recent advances in understanding connexin gap junction pathology in demyelinating diseases
Authors: Masaki Katsuhisa 
Published: March 2020

AbstractMultiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD) and Baló’s disease (BD) are inflammatory demyelinating diseases of the central nervous system. We previously reported that aquaporin‐4 antibody‐independent astrocytopathy can occur in heterogeneous demyelinating conditions. We focused on connexins (Cxs), which form gap junctions between astrocytes and oligodendrocytes to form the glial syncytium of the central nervous system. We investigated the pathological expression pattern of Cx43/Cx30 in astrocytes, and Cx47/Cx32 in oligodendrocytes in autopsied samples from MS, NMOSD and BD. Astrocytic Cx43 and oligodendrocytic Cx32/Cx47 were extensively diminished in both demyelinated and myelinated layers in all BD cases. Half of the NMOSD and MS cases showed preferential loss of astrocytic Cx43 in active demyelinating and chronic active lesions, where heterotypic Cx43/Cx47 astrocyte‐oligodendrocyte gap junctions were widely lost. Loss of Cx43 was frequently accompanied by distal oligodendrogliopathy, which is characterized by a preferential loss of myelin‐associated glycoprotein and apoptotic‐like oligodendrocytes. Isolated perivascular lesions in the spinal cord of NMOSD cases showed loss of aquaporin‐4 and Cx43, indicating early involvement of Cx43 in NMOSD. Neuronal and glial Cxs were affected in gray matter demyelination in MS and neurodegenerative diseases. Our findings show that Cx43 astrocytopathy and Cx47/Cx32 oligodendrogliopathy can be seen in MS, BD and NMOSD. Furthermore, the loss of astrocytic Cx43 might be associated with disease aggressiveness and distal oligodendrogliopathy in demyelinating conditions. Early disruption of glial gap junctions might disturb the glial syncytium and disrupt intercell communication, thereby inducing oligodendroglial injury and subsequent demyelination.
Beyond ‘developmentalism’: A relational and embodied approach to young children's development
Authors: Gabriel Norman 
Published: March 2020

AbstractThis article begins by discussing ‘developmentalism’, one of the key debates that has characterised the current theoretical impasse in the development of childhood studies. I use Norbert Elias's concept of the relation between love and learning as a foundation to develop the way in which young children's development is a non‐linear, temporal and embodied process. I argue that we need to develop a relational approach that moves beyond some of the binary divisions between ‘nature’ and ‘biology’, drawing on concepts from particular theoretical traditions that have been under‐utilised, particularly the relational school of psychoanalysis and the work of Maurice Merleau‐Ponty.