bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apoptotic Effects of a Thioether Analog of Vitamin K3 in a Human Leukemia Cell Line
Authors: Asami Satoru , Suzuki Mikana , Nakayama Toshimitsu , Shimoda Yasuyo , Miura Motofumi , Kato Koichi , Tokuda Eiichi , Ono Shinichi , Kawakubo Takashi , Nishizawa Kenji , Yamanaka Kenzo , Suzuki Takashi 
Published: October 2021

Research suggests that thioether analogs of vitamin K3 (VK3) can act to preserve the phosphorylation of epidermal growth factor receptors by blocking enzymes (phosphatases) responsible for their dephosphorylation. Additionally, these derivatives can induce apoptosis via mitogen-activated protein kinase and caspase-3 activation, inducing reactive oxygen species (ROS) production, and apoptosis. However, vitamin K1 exhibits only weak inhibition of phosphatase activity, while the ability of VK3 to cause oxidative DNA damage has raised concerns about carcinogenicity. Hence, in the current study, we designed, synthesized, and screened a number of VK3 analogs for their ability to enhance phosphorylation activity, without inducing off-target effects, such as DNA damage. 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay revealed that each analog produced a different level of cytotoxicity in the Jurkat human leukemia cell line; however, none elicited a cytotoxic effect that differed significantly from that of the control. Of the VK3 analogs, CPD5 exhibited the lowest EC50, and flow cytometry results showed that apoptosis was induced at final concentrations of ≥10 μM; hence, only 0.1, 1, and 10 μM were evaluated in subsequent assays. Furthermore, CPD5 did not cause vitamin K-attributed ROS generation and was found to be associated with a significant increase in caspase 3 expression, indicating that, of the synthesized thioether VK3 analogs, CPD5 was a more potent inducer of apoptosis than VK3. Hence, further elucidation of the apoptosis-inducing effect of CPD5 may reveal its efficacy in other neoplastic cells and its potential as a medication.
Gay Israeli Fathers: Reframing Societal Views on Surrogacy
Authors: Tsfati Maya , Ben-Ari Adital 
Published: October 2021

The present study aims to explore gay Israeli fathers’ responses and resistance to societal criticism on their decision to become parents through transnational surrogacy. The authors interviewed 39 Israeli gay men who became parents via transnational gestational surrogacy using in-depth, semistructured interviews. Analysis of the interviews suggest that the gay fathers responded to societal perceptions on their choice of surrogacy, which they interpreted as heterosexist and hostile, by relating them to Israeli dominant ideologies and constructing a counter discourse that frames surrogacy as an intimate process fostering gender and parental change. Yet, while the participants portray surrogacy as a catalyst for social change, their accounts are embedded within an Israeli context defined by pronatalist and neoliberal ideologies, showing how accounts of change are intertwined within hegemonic ideologies.
Vernal keratoconjunctivitis activity induces decrease of ocular surface CD14, TLR-4 and TLR-9 expression
Authors: Sacchetti Marta , Nebbioso Marcella , Segatto Marco , Abicca Irene , Bruscolini Alice , Zicari Anna Maria , Lambiase Alessandro 
Published: October 2021

Purpose: CD14 is involved in the modulation of immune reaction via toll-like receptors (TLR) and may influence the development of allergic diseases. The role of CD14 in vernal keratoconjunctivitis (VKC) has not yet been investigated. The aim of this study is to evaluate changes of tear soluble sCD14 and conjunctival CD14, TLR-4 and 9 expression in patients with VKC in the active and quiescent phases. Methods: Eighteen patients with VKC during active inflammation (group A, N = 9), in the quiescent phase (group Q, N = 5) and after recovery (group R, N = 4) and 10 healthy subjects were included. Expression of sCD14 in tears and of CD14, TLR-4, and TLR-9 by conjunctival epithelium were evaluated by Western Blot in all groups. Results: Expression of tear sCD14 and of conjunctival CD14, TLR-4, and TLR-9 was significantly decreased in group A when compared with healthy subjects and with VKC group Q and R. Lower expression of sCD14, CD14, TLR-4, and TLR-9 were significantly correlated with the severity of papillary reaction, while the lower sCD14 was correlated with severity of conjunctival hyperemia. Conclusions: Tear sCD14, and conjunctival CD14, TLR4, and TLR-9 decreased during ocular surface inflammatory reaction in patients with VKC. CD14 and TLRs ocular surface evaluation may represent biomarkers of VKC activity and novel therapeutic target.
Combined transconjunctival sutureless three-port vitrectomy and scleral fixation of intraocular lens
Authors: Danese Carla , Lanzetta Paolo 
Published: October 2021

Purpose The aim of this article is to describe an innovative and minimally invasive surgical technique for posterior vitrectomy combined with secondary intraocular lens implantation, using a sutureless scleral fixation Carlevale intraocular lens (I71 FIL SSF Carlevale lens. Soleko IOL Division, Italy). Methods The technique was conducted with only three transconjunctival sclerotomies and a corneal tunnel to perform intraocular lens explantation, posterior vitrectomy and Carlevale intraocular lens implantation. It is easier, quicker, and less invasive than the traditional technique with conjunctival peritomy, two scleral flaps and five sclerotomies. Results Surgery was performed uneventfully on three eyes of three patients. Two of them presented a luxation of the intraocular lens into the vitreous chamber, while one patient presented an intraocular lens subluxation. No complications were observed after a 5 to 8 months of follow-up. The intraocular lenses were well positioned, no conjunctival erosion was noted, and the intraocular pressure remained normal at all stages. Conclusions This is the first report of a combined procedure of IOL explantation, posterior vitrectomy and secondary IOL implantation using only three transconjunctival sclerotomies. This appears to be less invasive and it causes less discomfort to the patient. We suggest considering this technique in all those cases requiring a combined procedure in absence of a proper capsular support.
Predictors of adherence and persistence to disease-modifying therapies in Multiple Sclerosis
Authors: Zanga Gisela , Drzewiscki Estefania , Tagliani Paula , Smietniansky Maximiliano , Esnaola y Rojas Maria M. , Caruso Diego 
Published: October 2021

Background and Aims: In multiple sclerosis (MS), non-adherence/non-persistence is related to suboptimal response to treatment, including disease relapses and the need for more expensive healthcare. The aim of this study was to identify predictors related to adherence to disease modifying therapies (DMTs) in a cohort of Argentinian MS patients. Methods: We conducted a cross-sectional study at the National Medical Care Program from Argentina. MS patients with at least one claim for a DMT from 1 January 2017 to 1 October 2017 were identified. A telephone survey was performed to assess clinical and demographic factors. The medication possession ratio (MPR) was used to estimate adherence; MPR <80% defined non-adherence. Associations were studied using a logistic regression model. Results: Our database included 648 MS patients. A total of 360 patients (60% females, mean age 55.3 years) accepted to participate. Of these, 308 (85.5%) patients were receiving DMT at the time of the survey. Some 198 (63.7%) were receiving injectable therapies. Optimal adherence was 47.7%. Adherence was associated with oral medication [odds ratio (OR) 1.83 95% confidence interval (CI) 1.13–3.00, p = 0.014]. A factor related to oral drugs was higher educational level (OR 2.86 95%CI 1.41–5.81, p = 0.004). Conclusion: This real-world study showed better adherence and persistence on treatment with oral therapies in MS patients in Argentina.
Heterogeneity between proximal and distal aspects of occlusive thrombi on pretreatment imaging in acute ischemic stroke
Authors: Hashimoto Tetsuya , Kunieda Takenobu , Honda Tristan , Scalzo Fabien , Sharma Latisha K , Hinman Jason D , Rao Neal M , Nour May , Bahr-Hosseini Mersedeh , Saver Jeffrey L , Raychev Radoslav , Liebeskind David S 
Published: October 2021

Background The potential heterogeneity in occlusive thrombi caused by in situ propagation by secondary thrombosis after embolic occlusion could obscure the characteristics of original thrombi, preventing the clarification of a specific thrombus signature for the etiology of ischemic stroke. We aimed to investigate the heterogeneity of occlusive thrombi by pretreatment imaging. Methods Among consecutive stroke patients with acute embolic anterior circulation large vessel occlusion treated with thrombectomy, we retrospectively reviewed 104 patients with visible occlusive thrombi on pretreatment non-contrast computed tomography admitted from January 2015 to December 2018. A region of interest was set on the whole thrombus on non-contrast computed tomography under the guidance of computed tomography angiography. The region of interest was divided equally into the proximal and distal segments and the difference in Hounsfield unit densities between the two segments was calculated. Results Hounsfield unit density in the proximal segment was higher than that in the distal segment (mean difference 4.45; p < 0.001), regardless of stroke subtypes. On multivariate analysis, thrombus length was positively correlated (β = 0.25; p < 0.001) and time from last-known-well to imaging was inversely correlated (β = −0.0041; p = 0.002) with the difference in Hounsfield unit densities between the proximal and distal segments. Conclusions The difference in density between the proximal and distal segments increased as thrombi became longer and decreased as thrombi became older after embolic occlusion. This time/length-dependent thrombus heterogeneity between the two segments is suggestive of secondary thrombosis initially occurring on the proximal side of the occlusion.
Clinical frailty as a key characteristic of the patient population of the NHS Nightingale North West COVID-19 temporary emergency field hospital: cohort study April to June 2020
Authors: Trent Herdman M. , Seers Tim , Ng Cassandra , Davenport Rebecca , Sibley Sarah , Mannion Steve , Balasegaram Sooria , Redmond Anthony D 
Published: October 2021

Objectives COVID-19 temporary emergency ‘field’ hospitals have been established in the UK to support the surge capacity of the National Health Service while protecting the community from onward infection. We described the population of one such hospital and investigated the impact of frailty on clinical outcomes. Design Cohort study. Setting NHS Nightingale Hospital North West, April–June 2020. Participants All in-patients with COVID-19. Main Outcome Measures Mortality and duration of admission. Methods We analysed factors associated with mortality using logistic regression and admission duration using Cox's regression, and described trends in frailty prevalence over time using linear regression. Results A total of 104 COVID-19 patients were admitted, 74% with moderate-to-severe frailty (clinical frailty score, CFS > 5). A total of 84 were discharged, 14 transferred to other hospitals, and six died on site. High C-reactive protein (CRP) > 50 mg/dL predicted 30-day mortality (adjusted odds ratio 11.9, 95%CI 3.2–51.5, p < 0.001). Patients with CFS > 5 had a 10-day median admission, versus 7-day for CFS ≤ 5 and half the likelihood of discharge on a given day (adjusted hazard ratio 0.51, 95%CI 0.29–0.92, p  =  0.024). CRP > 50 mg/dL and hospital-associated COVID-19 also predicted admission duration. As more frail patients had a lower rate of discharge, prevalence of CFS > 5 increased from 64% initially to 90% in the final week (non-zero slope p < 0.001). Conclusions: The NNW population was characterized by high levels of frailty, which increased over the course of the hospital's operation, with subsequent operational implications. Identifying and responding to the needs of this population, and acknowledging the risks of this unusual clinical context, helped the hospital to keep patients safe.
On the Strategic Complementarity of Skilled Workers and Technological Innovation: Which Determines Which?
Authors: Accinelli Elvio , García Armando , Carrera Edgar J. Sánchez , Zazueta Jorge 
Published: October 2021

In this document, we analyse the strategic complementarity between technological investment and investment in training by workers. We show that, beyond the importance of the answer to the question about which factor determines which, initial minimal conditions in both factors are required to start a long-run social development process. If these minimums are not met, the economy can become a self-satisfied economy, with a social mediocre performance but, at least in the short run, successful from the individual point of view. We consider that either manager of firms as workers are rational agents who make decisions about their future behaviour, considering the current state of the economy, understanding for such, the percentage of innovative and non-innovative firms in the market and the percentage of skilled and unskilled workers in the labour market. While managers decide the best way to invest, workers decide whether to invest or not in the upgrade or in the development of their skills to face the new challenges posed by technological change. The evolution of the economy is summarized in a complex dynamical system represented by a coupled dynamical system very close to the replicator dynamics considered in evolutionary game theory. In this way, we show that the initial conditions play a crucial role to understand the possibilities of future performance of the economy in each country, and, on the other hand, we analyse the conditions that make possible or necessary the intervention of the government in the economy. JEL Classifications: C72, C73, O11, O55, K42
Unusual Findings in Trials Evaluating Adjuncts to Scaling and Root Planing: Meta-analysis (Part 1)
Authors: Gunsolley J.C. , Al-Abedalla K. , Shaqman M. , Ioannidou E. 
Published: October 2021

Background: A number of studies in patients with periodontitis have compared scaling and root planning (SRP) combined with an adjunctive treatment to SRP alone. Within that literature, an array of studies with overlapping investigators has consistently yielded substantially greater effects of adjunctive treatments than had been previously noted. This report investigates discrepancies between that cluster of research and the most recent American Dental Association (ADA) systematic review. Methods: This review was preregistered at https://osf.io/4meyd/ . A search using the Scopus platform identified 32 articles published from 2010 to 2017 by investigators affiliated with the Government Dental College and Research Institute (GDCRI) in Bangalore, India. The primary outcome used in this meta-analysis was the change in clinical attachment level (CAL) after 6 mo. Effect sizes were estimated using Comprehensive Meta-Analysis software after categorizing agents into groups based on pharmacologic similarity. Results: The search identified 32 studies encompassing 5 sets of adjunctive agents. Across the GDCRI studies, the CAL averaged 1.67 mm (95% confidence interval [CI]: 1.43–1.91 mm), substantially exceeding values reported in the ADA review (mean: 0.39 mm, 95% CI: 0.27–0.51 mm). For categories of studies in which comparable subgroup estimates were available, the evaluations yielded overlapping estimates of SRP alone, but CAL estimates were discrepant for both locally delivered antimicrobials (GDCRI studies: mean: 1.45 mm, 95% CI: 0.63–2.27 mm; ADA review: mean: 0.38 mm, 95% CI: 0.16 –0.60 mm) and systemic antibiotics (GDCRI studies: mean: 1.35 mm, 95% CI: 0.97–1.73 mm; ADA review: mean: 0.39 mm, 95% CI: 0.21–0.57 mm). Conclusion: In the literature on adjunctive agents supplementing SRP, findings from investigators linked to GDCRI stand out as having significantly more favorable estimated effects. Meanwhile, some agents studied by GDCRI-linked investigators have not been investigated by other researchers. In the absence of a clear explanation for discrepant results, it is recommended that unusually favorable reported effects of adjunctive agents be viewed with caution. Knowledge Transfer Statement: The present meta-analysis observed an unusually large effect size of adjunctive agents to scaling and root planning in studies conducted by the same research group. These results were not consistent with trials on adjunctive agents and previous reports. As this research group has exclusively tested most of the agents, their results must be viewed with caution until other independent groups replicate the studies and reproduce the effect size.
Missionaries from the Younger Churches
Authors: Orr Clara E. 
Published: October 2021

The assumption of responsibility for sending missionaries beyond the borders of their own countries has been in most cases a comparatively recent development in the life of the “younger churches”, Themselves the product of missions from churches longer established, they have obeyed the missionary imperative first at home and then have begun to share in the wider task. In some cases the young church arrived at this stage early, as in the South Seas; but conditions in other areas of the world are very different: some churches cannot yet send missionaries, others can help toward the support of missionaries sent by other agencies, and some now can support a growing program of foreign work. In previous reports prepared by the Missionary Research Library, some instances of the sending of missionaries by the younger churches were cited, but no documentation was specifically given. In the present report, considerably more material has been available, and sources are listed in the footnotes. There is no doubt that more missionaries have been sent by younger churches than are here reported. Some are sent by agencies of which the Missionary Research Library has no record; some are completely independent; some belong to groups which for one reason or another have not made information available. Insofar as replies have come in from national councils of churches and other field representatives, they have teen included. The many periodicals available in the Missionary Research Library have been found a fruitful source of currant information about the missionaries of the various churches, and some helpful data is also found in yearbooks and annuals. Special appreciation should be expressed to these who replied to the questionnaire sent to national Christian councils. Especially useful were the report and list of missionaries prepared in 1961 by the East Asia Christian cauncil, and the two current study books on Latin America. Further information and corrections from the field would be gladly received, in order that the record may more fairly reflection the actual situation, as the Church moves forward in her task.
Motivation for Mission
Authors: Skuse Jean 
Published: October 2021

Let us recognize at the outset that we are talking about a complex picture. Any generalization about “all missionaries” or “missionaries as a whole” is likely to be erroneous. We would also recognize that the role of mission is changing, and is constantly being re-examined in the light of new understandings and challenges. We would also admit that it is unlikely that there is a single motivation - that what drives people in different directions depends on so many of life's circumstances. And yet we need to examine our motives very carefully, to identify some as clearly being the wrong motives and to ask the question which was submitted to me for this paper: “How can we get ‘turned-on’ to do God's work today? Why is a Christian compelled to share what he/she knows of what God has done in Jesus Christ?” A motive, of course, is any consideration which moves the will, that which drives us to certain actions, and directs us towards particular goals. Motivation depends so much on the goal and vice versa. The two are almost inseparable. “Mission” or “missions” refer to the special task to which an individual or groups is destined. The usual connotation in the Christian Church involves being sent out by God or the church charged with responsibility for such functions as preaching the gospel, teaching the Word, healing the sick, proselytizing the heathen, and introducing the appropriate rites and ceremonies to accompany these functions. These are the traditional tasks of mission. We talk too of partnership in mission, sharing Christian communities, of involving ourselves in the secular processes. Our missionary motivation is intimately bound up with our understanding of what mission is all about. If we see mission as extending the Christian Church this will call forth one kind of motivation. If it is to be involved in the raising of the level of humanness of all God's creatures the motivation will be different.
Chimeric antigen receptor T-cell therapy in adults with B-cell acute lymphoblastic leukemia
Authors: Grover Punita , Veilleux Olivier , Tian Lu , Sun Ryan , Previtera Melissa , Curran Emily , Muffly Lori 
Published: October 2021

Abstract
Chimeric antigen receptor T-cell (CAR-T) therapy has transformed treatment paradigms for relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) in children and younger adults. We performed a systematic review to investigate the published literature on efficacy and toxicity of CAR-T therapy in adults with r/r B-ALL. We searched MEDLINE, Embase, and the Cochrane Library for prospective interventional studies and included published studies of ≥5 patients with median age at enrollment of ≥18 years. Risk of bias was assessed with a modified Institute of Health Economics tool. A total of 2566 records were assessed; 16 studies involving 489 patients were included in the final analysis. The mean complete remission (CR) rate was 81% and the measurable residual disease (MRD)–negative remission rate was 81% at 4 weeks after CAR-T infusion. With median follow-up across studies of 24 months, the cumulative 12-month probabilities of progression-free survival (PFS) and overall survival (OS) were 37% (95% CI, 26-48) and 57% (95% CI, 49-65), respectively. Relapse occurred in 40.3% of cases; target antigen was retained in 73.2% of relapses. Across studies, any grade of cytokine release syndrome (CRS) occurred in 82% of patients (95% CI, 61-95) and grade 3 or higher CRS in 27% (95% CI, 18-36). Neurotoxicity of any grade occurred in 34% of patients (95% CI, 24-47) and grade 3 or higher in 14% (95% CI, 1-25). In summary, CAR-T therapy achieves high early remission rates in adults with r/r B-ALL and represents a significant improvement over traditional salvage chemotherapy. Relapses are common and durable response remains a challenge.