bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and psychometric validation of the interRAI ChYMH externalizing subscale
Authors: Lau Chloe , Stewart Shannon L , Saklofske Donald H , Hirdes John
Published: October 2020

The interRAI Child and Youth Mental Health (ChYMH) is a standardized assessment instrument utilized in over 60 mental health agencies that promotes seamless transition across public healthcare sectors. The purpose of this study was to develop and assess the reliability and validity of the externalizing subscale on the interRAI Child and Youth Mental Health (ChYMH). Part one invited a panel of experts (i.e. doctoral-level clinical psychologists) to assess content validity of the items relevant to externalizing behaviors. Items that experts deemed representative of externalizing symptoms underwent unrestricted factor analyses in a sample of children/youths 4 to 18 years of age ( N = 3,464) collected across 39 mental health agencies. The final externalizing subscale showed strong content representativeness, high internal consistency, and good structural validity for a two-dimensional model of reactive and proactive externalizing behavior. In part two, Bayesian correlations demonstrated that the interRAI ChYMH externalizing subscale showed strong associations with externalizing subscales, anger, and disruptive behavior measures from various assessment instruments (i.e. Beck Youth Inventories, Social Skills Improvement System, Child and Adolescent Functional Assessment Scale, Child Behavior Checklist, Brief Child and Family Phone Interview). Overall, the externalizing subscale demonstrated strong measurement properties for the assessment of behavioral disturbances.
Doing being observed: Experimenting with collaborative focus group analysis in post-Umbrella Movement Hong Kong
Authors: Kong Sui-Ting , Ho Petula Sik-Ying , Jackson Stevi
Published: October 2020

Democratising social inquiry is particularly relevant in the context of Hong Kong’s recent social movements, where political divisions have created rifts among families and friends. In exploring the Umbrella Movement’s personal impact on activists, bystanders and opponents, we developed a new methodology: collaborative focus group analysis (CFGA). Designed to create a safe space for communicating political differences, the methodology also aims to break down the distinction between researchers and researched and engages the latter as co-researchers. In our first application of CFGA, solidarity was exhibited across political and cultural divides, demonstrating the methodology’s potential to support collaborative knowledge-making among co-researchers with different political stances and educational and cultural backgrounds. By analysing the patterns of interaction that emerged within CFGA, we identify strategies for building ‘situated solidarity’ and maintaining ‘non-hierarchical dialogues’. In so doing, we assess CFGA’s potential and limitations.
Filtering feminisms: Emergent feminist visibilities on Instagram
Authors: Savolainen Laura , Uitermark Justus , Boy John D.
Published: October 2020

Based on interviews with feminist Instagram users, this article studies emergent feminist visibilities on Instagram through the concept of filtering. Filtering entails both enhancement and subtraction: some feminist sensibilities align with Instagram’s interaction order, while others become subdued and remain at the margins of visibility. Taken together, users’ filtering practices contribute to the confident and happy image, individualistic streak, and accommodationist cast of popular feminism, while also amplifying feminist politics that affirm the pleasures of visibility and desire. Instagram proves a more challenging environment for feminists seeking to criticize competitive individualism and aesthetic norms. The notion of filtering enriches existing research on how online environments reconfigure feminist politics and problematizes the avowal of feminism in media culture.
Online bandwagon effects: Quantitative versus qualitative cues in online comments sections
Authors: Lee Seungae , Atkinson Lucy , Sung Yoon Hi
Published: October 2020

Bandwagon effects explain an individual’s tendency to conform to and follow other people’s opinions. Drawing on bandwagon effects, this study explored the relative influence of two different bandwagon heuristic cues in an online comments section (quantitative vs qualitative) on changes in news readers’ opinion. Study 1 revealed that qualitative cues have a stronger effect than quantitative cues in changing news readers’ opinions. Study 2 replicated the findings of Study 1 and showed that people change opinions in the same direction as perceived public opinion, providing empirical evidence of online bandwagon effects. The findings offer theoretical insights by explicating the process of opinion change via perceived public opinion as well as practical insights into public opinion formation in online environments.
Trauma exposure and post-traumatic stress disorder among regional journalists in Pakistan
Authors: Shah Sayyed Fawad Ali , Jan Faizullah , Ginossar Tamar , McGrail J. Patrick , Baber Danish , Ullah Rahman
Published: October 2020

This study sought to examine work-related exposure to trauma and predictors of Post-Traumatic Stress Disorder (PTSD) symptoms among regional journalists in the Khyber Pakhtunkhwa (KP) province, a conflict-ridden area in northwest Pakistan. We recruited 216 KP journalists. Analysis of the surveys revealed a high prevalence of trauma exposure and PTSD symptoms. All of the participants had covered at least one trauma inducing event. Exposure to work-related trauma, active emotional coping and avoidant emotional coping were statistically significant factors associated with PTSD symptoms. This study is the first to highlight the severity of the impact of trauma on regional journalists in Pakistan.
Dissecting news diversity: An integrated conceptual framework
Authors: Hendrickx Jonathan , Ballon Pieter , Ranaivoson Heritiana
Published: October 2020

News diversity is increasingly gaining momentum and relevance in academic research, but quantifying and qualifying the term remains problematic. This paper presents the results of a structured meta-synthesis literature review, in which all relevant publications dealing explicitly with news diversity, media diversity or content diversity of the 21st century found on Scopus ( n = 61) are coded and analysed. Findings reveal that studies dealing with these concepts are on the rise in absolute numbers, but also that their theoretical foundations predominantly still lie in the 1990s. From the viewpoint that said foundations have become inadequate to study and understand news diversity in the digital era, we propose an integrated conceptual framework, model and definition to operationalise news diversity, which takes into consideration recent changes in journalism as media concentration dynamics and changing patterns in news production and consumption. It does so by developing a typology of five categories of diversity (ownership, brand, production, content, consumption) and presenting three levels from which news diversity can be studied (the macro level of the media market, the meso level of the media company and the micro level of the media brand). Ultimately, the paper proposes the adoption of mixed methods research to reveal more about the characteristics, contexts and constraints within any media market.
The Use of an Adipofascial Flap to Prevent Extensor Tendon Adhesions After Plating of the Proximal Phalanx of the Fingers: A Comparative Study
Authors: Lucchina Stefano , D’Ambrosio Angelo , Fusetti Cesare , Guidi Marco
Published: October 2020

Background:

Extensor tendon adhesions occurring after proximal phalangeal (P1) fractures are not uncommon. A previous report described the use of an adipofascial flap (AFF) to prevent adhesions after dorsal plating of the P1. The purpose of the study is to examine the results of open reduction and internal fixation with the use of an AFF (F group) and without (N group, that is, no flap used) in a larger group of patients.

Methods:

A retrospective study involving a period of 11 years was conducted involving results of 21 unstable fractures of the P1 of the fingers in 18 patients. In all, 12 fingers were treated without any flap (N group) and 9 fingers were treated with the AFF (F group). For each patient, the total active motion (TAM) ratio, and the grip strength (Jamar) ratio were assessed, and adverse effects and the 10-point visual analogue scale (VAS) score were recorded. For statistical analysis, sample characteristics were described using mean ± standard deviation and median, and a Bayesian approach was used for inferential analysis.

Results:

In the F group, the TAM ratio (84% ± 13% vs 65% ± 17%) was higher with a lower rate of adverse effects (OR: 0.067, 95% CI, 0.0035-0.58,) and a lower VAS score with evidence of the positive effect of the AFF. The Jamar ratio was similar in the 2 groups (F group 80% ± 25% vs N group 79% ± 19%) with no associated effect of the AFF on grip strength.

Conclusions:

The AFF is a reliable tool to reduce adhesions between plates and the extensor apparatus of the P1 and may be useful to improve finger function after plating of P1 fractures.

Type of study/LOE:

Therapeutic, Retrospective, Level IV
Transient temperature field analysis of variable viscosity RTHSB with a special structural cavity
Authors: Ruan Jiafu , Wang Xigui , Ji ShuE , Wang Yongmei , An Siyuan
Published: October 2020

A radial thrust hydrodynamic sliding bearing (RTHSB) with special shaped cavity had been designed. Taking the instantaneous temperature rise characteristics of RTHSB as an analysis object, considering the influence of inlet lubricating oil velocity and transmission shaft speed, a dynamic simulation method of variable viscosity temperature field is proposed, and the mathematical model of instantaneous temperature rise of time-varying oil film is constructed. The correlation equation between instantaneous temperature rise and oil film variable viscosity is analyzed, the lubricating performance of a special-shaped cavity with variable thickness of the oil film considering real-time full operating conditions is revealed, and the alternating transient laws of oil film thickness with variable viscosity and its instantaneous temperature rise for no-load, heavy-load, and different rotating speeds are studied. It is obtained that the higher temperature area of profiled shaped cavity on reverse flow side extends to oil seal side with increase of rotating speed. The dynamic simulation of variable viscosity of RTHSB with different film thickness is simulated by using FLUENT software and the trend of transient film temperature field distribution of in special-shaped cavity is evaluated. The rationality of the mechanism analysis and numerical simulation results in this paper has been verified.
Freedom and Democracy: From Kant to Derrida
Authors: de Ville Jacques
Published: October 2020

The notion of freedom is synonymous with Kant, but where is it located, and what is the significance of its location for our understanding of democracy today? In this essay, an answer will be sought to these questions by way of Heidegger’s reading of Kant in The Essence of Human Freedom, followed by an exploration of Derrida’s radicalization of Heidegger’s reading in Rogues. If “freedom” is located beyond Being, as contended by both Heidegger and Derrida, a re-naming thereof is perhaps called for, a renaming, which would at the same time allow us to look beyond the variety of forms taken by democracy today, toward the democracy to come, which would no longer be characterized by mastery, sovereignty, and power, but instead by a welcoming of the unforeseeable and incalculable event.
On the Discursive-Material Enactment of Criminal Violence: How Death and Injury Come to Matter to the Criminal Law
Authors: Gilani Sabrina
Published: October 2020

This article seeks to challenge the prevailing view that violence is legally actionable because human bodies are capable of experiencing pain, injury, and death. Drawing on literature in the area of new materialism, this article demonstrates how pain, injury, and death are not ontological properties of the flesh-and-bone body, but rather, they are the effects of how violence is made sense-able, knowable, as part of the criminal legal process. Here, I examine four of the materializing practices through which violence becomes sense-able to us: crime scene photography, forensic pathology, legal judgments, and bodily performance. If the effects of criminal violence can be traced to the discursive practices by which we observe, measure, think, and speak about bodies, it becomes much harder to sustain the view that human violence is exceptional because the human body is special.
PD-L1 expression with respect to driver mutations in non-small cell lung cancer in an Asian population: a large study of 1370 cases in China
Authors: Li Caichen , Liu Jun , Xie Zhanhong , Zhu Feng , Cheng Bo , Liang Hengrui , Li Jianfu , Xiong Shan , Chen Zisheng , Liu Zhichao , Zhao Yi , Ou Limin , Zhong Ran , Wang Wei , Huang Jun , Sun Jinyun , Zhang Chunya , Weng Landong , He Jianxing , Liang Wenhua , Pan Zhenkui
Published: October 2020

Background:

Programmed cell death ligand 1 (PD-L1) expression with respect to genetic alternations has not been well established in non-small cell lung cancer (NSCLC), especially in the Asian population.

Methods:

We reviewed 1370 NSCLC patients from a prospectively maintained database. Immunohistochemistry was performed on tumor cells and tumor-infiltrating lymphocytes (TILs) using the VENTANA (SP142) anti-PD-L1 antibody. The tumor proportion score (TPS) cutoff values were set at ⩾1% and ⩾50%, and the immune proportion score (IPS) cutoff values were set at ⩾1% and ⩾10%.

Results:

In tumor cells, PD-L1 positivity was observed in 405 (29.6%), 122 (8.9%), and 27 (2.0%) patients with TPS cutoff values at ⩾1% and ⩾50%. Contrastingly, TILs of 1154 (84.2%) and 346 (25.3%) patients stained positive at IPS cutoff values of ⩾1% and ⩾50%, respectively. PD-L1 expression was more common in patients who were mutation-negative irrespective of the TPS cutoff values and tumor size. PD-L1 expression in tumor cells was less frequent in patients harboring EGFR mutations (18.8% TPS ⩾ 1% and 4.6% TPS ⩾ 50%). Conversely, PD-L1 expression was high in the presence of KRAS mutations (47.3% TPS ⩾ 1% and 22.5% TPS ⩾ 50%). Overall, KRAS, BRAF, PICK3A, MET mutations and ROS1 and RET translocations were more frequent, while EGFR and HER2 mutations and ALK translocations were less frequent compared with the overall PD-L1 expression levels. Although the difference between TILs among the PD-L1-positive cases was comparatively small, PD-L1 positivity was less prevalent in EGFR-mutated tumors and more common in those with KRAS mutations, ROS1 translocations, BRAF mutations, or MET mutations.

Conclusion:

Our study showed the heterogeneity in PD-L1 expression with respect to nine major oncogenic drivers in China. Future studies are warranted to further clarify the association between PD-L1 expression and driver mutations in NSCLC.
Systematic review of first-line chemotherapy for chemo-naïve extensive-stage small-cell lung cancer: network meta-analysis
Authors: Chen Hao , Horita Nobuyuki , Ito Kentaro , Nagakura Hideyuki , Hara Yu , Kobayash Nobuaki , Yamamoto Masaki , Kudo Makoto , Kaneko Takeshi
Published: October 2020

Background:

Our goal was to organize the data from randomized controlled trials that evaluated first-line chemotherapy for chemo-naïve extensive disease small-cell lung cancer (ED-SCLC).

Methods:

The protocol following PRISMA methodology was submitted as PROSPERO 154049. We included individually randomized trials comparing two or more chemotherapy regimens as the first-line treatment for chemo-naïve ED-SCLC regardless of the age, sex, performance status, co-morbidities, and organ functions written in the English language since 2000. Molecular targeted agents and immune checkpoint inhibitors were considered chemotherapy along with cytotoxic medications. We pooled the logarithm of hazard ratio (HR) and its standard error using the frequentist weighted least squares approach random-model network meta-analysis.

Results:

A total of 46 eligible trials that involved 11,987 patients were included. The primary endpoint, HR of overall survival (OS, HRos) of the selected comparisons was as follows: carboplatin+amrubicin (HRos 0.56, 95% confidence interval (CI) 0.33–0.96), carboplatin+etoposide+atezolizumab (HRos 0.70, 95% CI 0.53–0.92), and carboplatin+irinotecan (HRos 0.73, 95% CI 0.58–0.91) were compared with carboplatin+etoposide. The carboplatin+etoposide+atezolizumab regimen was compared with carboplatin+irinotecan (HRos 0.97, 95% CI 0.68–1.37) and cisplatin+irinotecan regimen (HRos 0.87, 95% CI 0.58–1.31). “Selective carboplatin or cisplatin (CBDCA/CDDP)”+etoposide+durvalumab was compared with CBDCA/CDDP+etoposide (HRos 0.73, 95% CI 0.59–0.91). Platinum+etoposide+durvalumab was compared with platinum+irinotecan (HRos 0.88, 95% CI 0.67–1.15). Cumulative meta-analysis suggested that platinum+irinotecan was associated with better OS than platinum+etoposide as of 2010 through 40 out of 46 trials in our review that used platinum+etoposide as a reference regimen.

Conclusion:

Patients treated with carboplatin+amrubicin, carboplatin+etoposide+atezolizumab, CBDCA/CDDP+etoposide+durvalumab, and platinum+irinotecan showed better HRos than those treated with platinum+etoposide, one of the standard regimens.
Electrical muscle stimulation intervention in the acute phase of neuromyelitis optica: Two case reports
Authors: Michiue Kana , Nishikawa Yuichi
Published: October 2020

The aim of this study was to examine the effect of electrical muscle stimulation on muscle atrophy caused by neuromyelitis optica. Two neuromyelitis optica patients with flaccid paralysis participated. The participants underwent a general rehabilitation program (transfer, balance, and gait training) and electrical muscle stimulation on the quadriceps femoris muscle of their paralyzed side. The change in the thickness of the vastus lateralis muscle ranged from −0.6 to 1.4 mm. These changes were minimal and did not indicate muscle atrophy. These findings suggest that in addition to general physiotherapy, electrical muscle stimulation seems safe and feasible in the acute phase of neuromyelitis optica.
Patient Suffering in Chronic Digestive Diseases: Will Primary Care-Specialist Collaboration With Effective Interactive Communication and Integrative Medicine in the Plan of Care Improve Quality of Life?
Authors: Thomas Andrew , Thomas Annie
Published: October 2020

Acute and chronic digestive diseases are causing increased burden to patients and are increasing the United States health care spending. The purpose of this case report was to present how nonconfirmatory and conflicting diagnoses led to increased burden and suffering for a patient thus affecting quality of life. There were many physician visits and multiple tests performed on the patient. However, the primary care physician and specialists could not reach a confirmatory diagnosis. The treatment plans did not offer relief of symptoms, and the patient continues to experience digestive symptoms, enduring this burden for over 2 years. The central theme of this paper is to inform health care providers the importance of utilizing evidence-based primary care specialist collaboration models for better digestive disease outcomes. Consistent with patient’s experience, the authors propose to pilot/adopt the integrative health care approaches that are proven effective for treating digestive diseases.
Assessing Professionalism in Medicine – A Scoping Review of Assessment Tools from 1990 to 2018
Authors: Tay Kuang Teck , Ng Shea , Hee Jia Min , Chia Elisha Wan Ying , Vythilingam Divya , Ong Yun Ting , Chiam Min , Chin Annelissa Mien Chew , Fong Warren , Wijaya Limin , Toh Ying Pin , Mason Stephen , Krishna Lalit Kumar Radha
Published: October 2020

Background:

Medical professionalism enhances doctor-patient relationships and advances patient-centric care. However, despite its pivotal role, the concept of medical professionalism remains diversely understood, taught and thus poorly assessed with Singapore lacking a linguistically sensitive, context specific and culturally appropriate assessment tool. A scoping review of assessments of professionalism in medicine was thus carried out to better guide its understanding.

Methods:

Arksey and O’Malley’s (2005) approach to scoping reviews was used to identify appropriate publications featured in four databases published between 1 January 1990 and 31 December 2018. Seven members of the research team employed thematic analysis to evaluate the selected articles.

Results:

3799 abstracts were identified, 138 full-text articles reviewed and 74 studies included. The two themes identified were the context-specific nature of assessments and competency-based stages in medical professionalism.

Conclusions:

Prevailing assessments of professionalism in medicine must contend with differences in setting, context and levels of professional development as these explicate variances found in existing assessment criteria and approaches. However, acknowledging the significance of context-specific competency-based stages in medical professionalism will allow the forwarding of guiding principles to aid the design of a culturally-sensitive and practical approach to assessing professionalism.
BAX 335 hemophilia B gene therapy clinical trial results: potential impact of CpG sequences on gene expression
Authors: Konkle Barbara A. , Walsh Christopher E. , Escobar Miguel A. , Josephson Neil C. , Young Guy , von Drygalski Annette , McPhee Scott W. J. , Samulski R. Jude , Bilic Ivan , de la Rosa Maurus , Reipert Birgit M. , Rottensteiner Hanspeter , Scheiflinger Friedrich , Chapin John C. , Ewenstein Bruce , Monahan Paul E.
Published: October 2020

Gene therapy has the potential to maintain therapeutic blood clotting factor IX (FIX) levels in patients with hemophilia B by delivering a functional human F9 gene into liver cells. This phase 1/2, open-label dose-escalation study investigated BAX 335 (AskBio009, AAV8.sc-TTR-FIXR338Lopt), an adeno-associated virus serotype 8 (AAV8)–based FIX Padua gene therapy, in patients with hemophilia B. This report focuses on 12-month interim analyses of safety, pharmacokinetic variables, effects on FIX activity, and immune responses for dosed participants. Eight adult male participants (aged 20-69 years; range FIX activity, 0.5% to 2.0%) received 1 of 3 BAX 335 IV doses: 2.0 × 1011; 1.0 × 1012; or 3.0 × 1012 vector genomes/kg. Three (37.5%) participants had 4 serious adverse events, all considered unrelated to BAX 335. No serious adverse event led to death. No clinical thrombosis, inhibitors, or other FIX Padua–directed immunity was reported. FIX expression was measurable in 7 of 8 participants; peak FIX activity displayed dose dependence (32.0% to 58.5% in cohort 3). One participant achieved sustained therapeutic FIX activity of ∼20%, without bleeding or replacement therapy, for 4 years; in others, FIX activity was not sustained beyond 5 to 11 weeks. In contrast to some previous studies, corticosteroid treatment did not stabilize FIX activity loss. We hypothesize that the loss of transgene expression could have been caused by stimulation of innate immune responses, including CpG oligodeoxynucleotides introduced into the BAX 335 coding sequence by codon optimization. This trial was registered at www.clinicaltrials.gov as #NCT01687608.
High frequency of clonal hematopoiesis in Erdheim-Chester disease
Authors: Cohen Aubart Fleur , Roos-Weil Damien , Armand Marine , Marceau-Renaut Alice , Emile Jean-François , Duployez Nicolas , Charlotte Frédéric , Poulain Stéphanie , Lhote Raphael , Hélias-Rodzewicz Zofia , Della-Valle Véronique , Bernard Olivier , Maloum Karim , Nguyen-Khac Florence , Donadieu Jean , Amoura Zahir , Abdel-Wahab Omar , Haroche Julien
Published: October 2020

Erdheim-Chester disease (ECD) is a clonal hematopoietic disorder characterized by the accumulation of foamy histiocytes within organs (in particular, frequent retroperitoneal involvement) and a high frequency of BRAFV600E mutations. Although ECD is not commonly recognized to have overt peripheral blood (PB) or bone marrow (BM) disease, we recently identified that ECD patients have a high frequency of a concomitant myeloid malignancy. We thus conducted a systematic clinical and molecular analysis of the BM from 120 ECD patients. Surprisingly, 42.5% of ECD patients (51 of 120) had clonal hematopoiesis whereas 15.8% of patients (19 of 120) developed an overt hematologic malignancy (nearly all of which were a myeloid neoplasm). The most frequently mutated genes in BM were TET2, ASXL1, DNMT3A, and NRAS. ECD patients with clonal hematopoiesis were more likely to be older (P < .0001), have retroperitoneal involvement (P = .02), and harbor a BRAFV600E mutation (P = .049) than those without clonal hematopoiesis. The presence of the TET2 mutation was associated with a BRAFV600E mutation in tissue ECD lesions (P = .0006) and TET2-mutant ECD patients were more likely to have vascular involvement than TET2 wild-type ECD patients. Clonal hematopoiesis mutations in ECD were detected in cells derived from CD34+CD38− BM progenitors and PB monocytes but less frequently present in PB B and T lymphocytes. These data identify a heretofore unrecognized high frequency of clonal hematopoiesis in ECD patients, reaffirm the development of additional high risk of myeloid neoplasms in ECD, and provide evidence of a BM-based precursor cell of origin for many patients with ECD.
Evaluation of Longitudinal Pain Study in Sickle Cell Disease (ELIPSIS) by patient-reported outcomes, actigraphy, and biomarkers
Authors: Pittman Debra D. , Hines Patrick C. , Beidler David , Rybin Denis , Frelinger Andrew L. , Michelson Alan D. , Liu Ke , Gao Xiufeng , White Jennell , Zaidi Ahmar U. , Charnigo Robert J. , Callaghan Michael U.
Published: October 2020

Clinical trials in sickle cell disease (SCD) often focus on health care utilization for painful vaso-occlusive crises (VOCs). However, no objective, quantifiable pain biomarkers exist, pain is not specific to VOCs, health care utilization varies between patients, unreported at-home VOCs likely contribute to long-term outcomes, and patient-reported outcomes are seldom considered. This noninterventional, longitudinal, 6-month study aimed to develop tools to identify VOCs in SCD patients with or without health care utilization. Participants wore an actigraph device, tracking sleep and activity. Patients with SCD used an electronic patient-reported outcome (ePRO) tool to collect data on pain, medication, fatigue, and daily function. Patients self-reported when they experienced VOC pain (VOC day). Biomarkers were collected every 3 weeks (non-VOC). Self-reported VOCs triggered at-home or in-hospital blood collection. The study enrolled 37 participants with SCD; 35 completed the study. Participants reported 114 VOC events and 346 VOC days, of which 62.3% and 78.3%, respectively, were self-treated at home. The ePRO and actigraphy captured end points of pain, functionality, fatigue, activity, and sleep; each was significantly altered on VOC days compared with non-VOC days. Biomarkers collected at home or in the hospital on VOC days were significantly altered compared with non-VOC baseline values, including leukocyte-platelet aggregates, microfluidic-based blood cell adhesion, interleukin-6, C-reactive protein, interleukin-10, tumor necrosis factor-α, and thrombin–antithrombin. The Evaluation of Longitudinal Pain Study in Sickle Cell Disease (ELIPSIS) trial shows the feasibility of accurately monitoring out-of-hospital pain by using patient-reported VOC days as potential end points for clinical trials in SCD; it describes the changes in biomarkers and activity measured by actigraphy that may enable improved identification and assessment of VOCs.
An epitope-based approach of HLA-matched platelets for transfusion: a noninferiority crossover randomized trial
Authors: Marsh Judith C. , Stanworth Simon J. , Pankhurst Laura A. , Kallon Delordson , Gilbertson Adeline Z. , Pigden Collette , Deary Alison J. , Mora Ana S. , Brown Joanne , Laing Emma S. , Choo Louise L. , Hodge Renate , Llewelyn Charlotte A. , Harding Kay , Sage Deborah , Mijovic Aleksandar , Mufti Ghulam J. , Navarrete Cristina V. , Brown Colin J.
Published: October 2020

Platelet transfusion refractoriness results in adverse outcomes and increased health care costs. Managing refractoriness resulting from HLA alloimmunization necessitates the use of HLA antigen–matched platelets but requires a large platelet donor pool and does not guarantee full matching. We report the first randomized, double-blind, noninferiority, crossover trial comparing HLA epitope–matched (HEM) platelets with HLA standard antigen–matched (HSM) platelet transfusions. Alloimmunized, platelet-refractory, thrombocytopenic patients with aplastic anemia, myelodysplastic syndrome, or acute myeloid leukemia were eligible. HEM platelets were selected using HLAMatchMaker epitope (specifically eplet) matching. Patients received up to 8 prophylactic HEM and HSM transfusions provided in random order. The primary outcome was 1-hour posttransfusion platelet count increment (PCI). Forty-nine patients were randomized at 14 UK hospitals. For intention to treat, numbers of evaluable transfusions were 107 and 112 for HEM and HSM methods, respectively. Unadjusted mean PCIs for HEM and HSM methods were 23.9 (standard deviation [SD], 15) and 23.5 (SD, 14.1), respectively (adjusted mean difference, −0.1; 95% confidence interval [CI], −2.9 to 2.8). Because the lower limit of the 95% CI was not greater than the predefined noninferiority limit, the HEM approach was declared noninferior to the HSM approach. There were no differences in secondary outcomes of platelet counts, transfusion requirements, and bleeding events. Adequate 1-hour PCI was more frequently observed, with a mean number of 3.2 epitope mismatches, compared with 5.5 epitope mismatches for inadequate 1-hour increments. For every additional epitope mismatch, the likelihood of an adequate PCI decreased by 15%. Epitope-matched platelets should be considered to support HLA alloimmunized patients. This trial was registered at www.isrctn.com as #ISRCTN23996532.
A phase 1 study of inotuzumab ozogamicin in pediatric relapsed/refractory acute lymphoblastic leukemia (ITCC-059 study)
Authors: Brivio Erica , Locatelli Franco , Lopez-Yurda Marta , Malone Andrea , Díaz-de-Heredia Cristina , Bielorai Bella , Rossig Claudia , van der Velden Vincent H. J. , Ammerlaan Anneke C. J. , Thano Adriana , van der Sluis Inge M. , den Boer Monique L. , Chen Ying , Sleight Barbara , Brethon Benoit , Nysom Karsten , Sramkova Lucie , Øra Ingrid , Vinti Luciana , Chen-Santel Christiane , Zwaan Christian Michel
Published: October 2020

This phase 1 study investigated the recommended phase 2 dose (RP2D) of inotuzumab ozogamicin (InO), a CD22-directed antibody-drug conjugate, in pediatric patients with multiple relapsed/refractory (R/R) CD22+ acute lymphoblastic leukemia (ALL). Patients (age ≥1 year or <18 years) received 3 doses of InO (days 1, 8, and 15) per course. Dose escalation was based on dose-limiting toxicities (DLTs) during course 1. Dose level 1 (DL1) was 1.4 mg/m2 (0.6, 0.4, 0.4 mg/m2) and DL2 was 1.8 mg/m2 (0.8, 0.5, 0.5 mg/m2). Secondary end points included safety, antileukemic activity, and pharmacokinetics. Twenty-five patients (23 evaluable for DLTs) were enrolled. In course 1, the first cohort had 1 of 6 (DL1) and 2 of 5 (DL2) patients who experienced DLTs; subsequent review considered DL2 DLTs to be non–dose-limiting. Dose was de-escalated to DL1 while awaiting protocol amendment to re-evaluate DL2 in a second cohort, in which 0 of 6 (DL1) and 1 of 6 (DL2) patients had a DLT. Twenty-three patients experienced grade 3 to 4 adverse events; hepatic sinusoidal obstruction syndrome was reported in 2 patients after subsequent chemotherapy. Overall response rate after course 1 was 80% (95% confidence interval [CI], 59% to 93%) (20 of 25 patients; DL1: 75% [95% CI, 43% to 95%], DL2: 85% [95% CI, 55% to 98%]). Of the responders, 84% (95% CI, 60% to 97%) achieved minimal residual disease (MRD)-negative complete response, and 12-month overall survival was 40% (95% CI, 25% to 66%). Nine patients received hematopoietic stem cell transplantation or chimeric antigen receptor T cells after InO. InO median maximum concentrations were comparable to simulated adult concentrations. InO was well tolerated, demonstrating antileukemic activity in heavily pretreated children with CD22+ R/R ALL. RP2D was established as 1.8 mg/m2 per course, as in adults. This trial was registered at https://www.clinicaltrialsregister.eu as EUDRA-CT 2016-000227-71.
Incidence, risk factors, and outcomes of venous and arterial thromboembolism in immune checkpoint inhibitor therapy
Authors: Moik Florian , Chan Wei-Shin Evelyn , Wiedemann Sarah , Hoeller Christoph , Tuchmann Felix , Aretin Marie-Bernadette , Fuereder Thorsten , Zöchbauer-Müller Sabine , Preusser Matthias , Pabinger Ingrid , Ay Cihan
Published: October 2020

The risk of venous thromboembolism (VTE) and arterial thromboembolism (ATE) associated with immune checkpoint inhibitors is currently unclear. Our aim was to quantify the risk of VTE/ATE in patients with cancer treated with immune checkpoint inhibitors, explore clinical impact, and investigate potential clinical risk factors. Patients treated with immune checkpoint inhibitors at the Medical University of Vienna from 2015 to 2018 were identified using in-house pharmacy records (n = 672; most frequent entities: 30.4% melanoma, 24.1% non-small cell lung cancer; 86% stage IV disease). A retrospective chart review was performed to screen for VTE and/or ATE. Cumulative incidences and between-group differences were estimated in competing-risk analysis. The impact of VTE/ATE on mortality was studied by multistate modelling. Over a median follow-up of 8.5 months, 47 VTEs and 9 ATEs were observed. Cumulative incidences of VTE and ATE were 12.9% (95% confidence interval [CI], 8.2-18.5) and 1.8% (95% CI, 0.7-3.6). Occurrence of VTE was associated with increased mortality (transition hazard ratio, 3.09; 95% CI, 2.07-4.60). History of VTE predicted VTE occurrence (subdistribution hazard ratio [SHR], 3.69; 95% CI, 2.00-6.81), and distant metastasis was nonsignificantly associated with VTE risk (SHR, 1.71; 95% CI, 0.62-4.73). No association of VTE with Eastern Cooperative Oncology Group performance status, Charlson comorbidity index, or Khorana score was observed, and rates of VTE were comparable between tumor types and checkpoint-inhibitory agents. In conclusion, patients with cancer under immune checkpoint inhibitor therapy are at high risk of thromboembolism, especially VTE. Furthermore, VTE occurrence was associated with increased mortality.
Nanotechnology approaches to addressing HER2-positive breast cancer
Authors: White Bryan E. , White Molly K. , Adhvaryu Het , Makhoul Issam , Nima Zeid A. , Biris Alexandru S. , Ali Nawab
Published: October 2020

Breast cancer is a major cause of cancer-associated deaths in the United States. It was estimated that 12% of women in the U.S. will develop invasive breast cancer in their lifetime. The human epidermal growth factor receptor (HER2/neu) is a growth-promoting protein that is overexpressed in 15–20% of breast cancers (HER2-positive breast cancer). HER2-positive breast cancer generally grows and spreads more quickly than other breast cancers, but it can be targeted therapeutically. Targeting drugs have been developed with a specific design to stop the growth and even the spread of cancer. These drugs include trastuzumab (Herceptin), pertuzumab (Perjeta), ado-trastuzumab emtansine (Kadcyla, or TDM-1), fam-trastuzumab deruxtecan, lapatinib, neratinib and tucatinib. However, the need for better targeted therapy and efficacy still exists. Nanotechnology could have major advantages in terms of detection, targeting, drug delivery, and destruction of cancer cells and tumors. Although a great deal of progress has been accomplished major challenges still need to be addressed. In this review, we examine the major areas of research in the area of nanotechnology and HER2-positive breast cancer.
Genome-wide analysis and prediction of genes involved in the biosynthesis of polysaccharides and bioactive secondary metabolites in high-temperature-tolerant wild Flammulina filiformis
Authors: Chen Juan , Li Jia-Mei , Tang Yan-Jing , Ma Ke , Li Bing , Zeng Xu , Liu Xiao-Bin , Li Yang , Yang Zhu-Liang , Xu Wei-Nan , Xie Bao-Gui , Liu Hong-Wei , Guo Shun-Xing
Published: October 2020

Background

Flammulina filiformis (previously known as Asian F. velutipes) is a popular commercial edible mushroom. Many bioactive compounds with medicinal effects, such as polysaccharides and sesquiterpenoids, have been isolated and identified from F. filiformis, but their biosynthesis and regulation at the molecular level remains unclear. In this study, we sequenced the genome of the wild strain F. filiformis Liu355, predicted its biosynthetic gene clusters (BGCs) and profiled the expression of these genes in wild and cultivar strains and in different developmental stages of the wild F. filiformis strain by a comparative transcriptomic analysis.

Results

We found that the genome of the F. filiformis was 35.01 Mb in length and harbored 10,396 gene models. Thirteen putative terpenoid gene clusters were predicted and 12 sesquiterpene synthase genes belonging to four different groups and two type I polyketide synthase gene clusters were identified in the F. filiformis genome. The number of genes related to terpenoid biosynthesis was higher in the wild strain (119 genes) than in the cultivar strain (81 genes). Most terpenoid biosynthesis genes were upregulated in the primordium and fruiting body of the wild strain, while the polyketide synthase genes were generally upregulated in the mycelium of the wild strain. Moreover, genes encoding UDP-glucose pyrophosphorylase and UDP-glucose dehydrogenase, which are involved in polysaccharide biosynthesis, had relatively high transcript levels both in the mycelium and fruiting body of the wild F. filiformis strain.

Conclusions

F. filiformis is enriched in a number of gene clusters involved in the biosynthesis of polysaccharides and terpenoid bioactive compounds and these genes usually display differential expression between wild and cultivar strains, even in different developmental stages. This study expands our knowledge of the biology of F. filiformis and provides valuable data for elucidating the regulation of secondary metabolites in this unique F. filiformis strain.
Combination of modified carbapenem inactivation method (mCIM) and EDTA-CIM (eCIM) for phenotypic detection of carbapenemase-producing Enterobacteriaceae
Authors: Tsai Ya-Min , Wang Shining , Chiu Hui-Chuan , Kao Cheng-Yen , Wen Li-Li
Published: October 2020

Background

Carbapenemase-resistant Enterobacteriaceae (CRE) cause many serious infections resulting in increasing treatment cost, prolonged hospitalization, and mortality rate. Reduced expression and/or mutations of porins and the presence of carbapenemase promote Enterobacteriaceae survival under carbapenem treatments. Development of accurate methods for the detection of antimicrobial resistance is required not only for therapy but also to monitor the spread of resistant bacteria or resistance genes throughout the hospital and community. In this study, we aimed to evaluate the phenotypic methods, Modified Hodge test (MHT), modified carbapenem inactivation method (mCIM), and EDTA-CIM (eCIM) for the detection of carbapenemase-producing Enterobacteriaceae (CPE).

Results

The results showed that mCIM had a sensitivity of 100% and a specificity of 100%, whereas the MHT had a sensitivity of 84.8% and a specificity of 97.8% for the 195 CRE isolates tested (105 CPE and 90 non-CPE isolates). The sensitivity of the mCIM/eCIM to detect metallo-carbapenemases in this study was 89.3% and the specificity was 98.7% as compared to the genotypic PCR detection.

Conclusions

These findings indicate that the mCIM combined with eCIM is useful for detecting and distinguishing different types of carbapenemase in Enterobacteriaceae.
Changes in hepatic fibrosis and vitamin D levels after viral hepatitis C eradication using direct-acting antiviral therapy
Authors: Sriphoosanaphan Supachaya , Thanapirom Kessarin , Suksawatamnuay Sirinporn , Thaimai Panarat , Sittisomwong Sukanya , Sonsiri Kanokwan , Srisoonthorn Nunthiya , Teeratorn Nicha , Tanpowpong Nattaporn , Chaopathomkul Bundit , Treeprasertsuk Sombat , Poovorawan Yong , Komolmit Piyawat
Published: October 2020

Background

Vitamin D (VD) is important in hepatic fibrogenesis in animal models and human studies. VD deficiency is associated with liver fibrosis progression. Metabolic dysfunction of the liver, as an intermediate organ for VD metabolism, contributes partly to this deficiency. We hypothesized that improving hepatic fibrosis and inflammation in chronic hepatitis C (CHC) patients after eradication with direct-acting antivirals (DAA) would increase 25-hydroxyVD [25(OH)VD] levels.

Methods

Eighty CHC patients (17 chronic hepatitis, and 63 cirrhosis) were enrolled. Baseline characteristics, hepatitis C viral load (VL), genotypes, liver enzymes and liver stiffness measurements (LSM) were assessed at baseline. Blood samples for 25(OH)VD and the procollagen type III N-terminal peptide (P3NP) were collected at baseline, 24 and 48 weeks. LSMs were re-evaluated at 48 weeks. Serum 25(OH)VD levels < 30 ng/mL were defined as VD insufficiency/deficiency. Paired t-tests were used for statistical analyses.

Results

Among 80 patients, the mean age was 57.7 ± 10.5 years, and 52.5% were men. The mean VL was 6.1 ± 0.7 logIU/mL with genotype 1 predominance (55%). All patients achieved sustained virological response. The alanine aminotransferase levels decreased from 79.9 ± 53.3 U/L at baseline to 25.7 ± 17.2 and 22.3 ± 11.0 U/L at 24 and 48 weeks, respectively (p < 0.001). The mean LSM decreased from 19.2 ± 15.3 to 11.7 ± 8.0 kPa at 48 weeks (p < 0.001). The P3NP levels decreased from 43.6 ± 22.0 ng/mL before treatment to 35.7 ± 21.1 and 29.4 ± 15.0 ng/mL at 24 and 48 weeks, respectively (p < 0.001). The proportions of VD insufficiency/deficiency were 72.5%, 91.3%, and 86.5% at baseline, 24 and 48 weeks, respectively. The 25(OH)VD levels decreased from 26.3 ± 10.7 ng/mL at baseline to 20.8 ± 8.1 and 20.8 ± 8.5 ng/mL at 24 and 48 weeks, respectively (p < 0.001).

Conclusions

Curative treatment with DAA attenuated the liver stiffness and inflammation but did not improve VD levels. Over 80% of patients remained VD insufficient/deficient. Whether VD replacement during and after DAA therapy can improve hepatic fibrosis remains unclear.

Trial registration The Thai Clinical Trial Registry as TCTR20161025001 (31 October 2016). http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=2136.
Completeness of tuberculosis case notifications in Germany in 2013–2017: first results of an inventory study
Authors: Domaszewska Teresa , Karo Basel , Preuss Ute , Kollan Christian , Reuss Annicka , Blank Hans-Peter , Brodhun Bonita , Hauer Barbara , Altmann Doris , Fiebig Lena , Haas Walter , Perumal Nita
Published: October 2020

Background

Evaluating the completeness of tuberculosis (TB) notification data is important for monitoring of TB surveillance systems. We conducted an inventory study to calculate TB underreporting in Germany in 2013–2017.

Methods

Acquisition of two pseudonymized case-based data sources (national TB notification data and antibiotic resistance surveillance data) was followed by two-source Capture-recapture (CRC) analysis, as case-based data from a third source was unavailable. Aggregated data on consumption of a key anti-TB drug (pyrazinamide [PZA]) was compared to an estimated need for PZA based on TB notification data to obtain an independent underreporting estimation. Additionally, notified TB incidence was compared to TB rate in an aggregated health insurance fund dataset.

Results

CRC and PZA-based approaches indicated that between 93 and 97% (CRC) and between 91 and 95% (PZA) of estimated cases were captured in the national TB notification data in the years 2013–2017. Insurance fund dataset did not indicate TB underreporting on the national level in 2017.

Conclusions

Our results suggest that more than 90% of estimated TB cases are captured within the German TB surveillance system, and accordingly the TB notification rate is likely a good proxy of the diagnosed TB incidence rate. An increase in underreporting and discrepancies however should be further investigated.
Septic arthritis of the shoulder due to Ureaplasma urealyticum after emergency caesarean section: a case report
Authors: Mahlouly Jaad , Lhopitallier Loic , Suttels Véronique , Mueller Linda , Wernly Diane , Borens Olivier , Steinmetz Sylvain
Published: October 2020

Background

Ureaplasma urealyticum is an intra-cellular bacterium frequently found colonizing the genital tract. Known complications include localized infections, which can result in premature deliveries. Septic arthritis due to U. urealyticum in healthy patients is exceptionally rare, although opportunistic septic arthritis in agammaglobulinemic patients have been reported. However, there are no reports of septic arthritis due to U. urealyticum following caesarean section or in the post-partum period.

Case presentation

A 38-year-old immunocompetent woman presented with severe right shoulder pain, 1 month following emergency caesarean section at 26 weeks of gestation for pre-eclampsia and spontaneous placental disruption with an uncomplicated post-operative recovery.

Our suspicion of septic arthritis was confirmed with abundant pus following arthrotomy by a delto-pectoral approach. Awaiting culture results, empirical antibiotic treatment with intravenous amoxicilline and clavulanic acid was initiated. In spite of sterile cultures, clinical evolution was unfavorable with persistent pain, inflammation and purulent drainage, requiring two additional surgical débridement and lavage procedures.

The 16S ribosomal RNA PCR of the purulent liquid was positive for U. urealyticum at 2.95 × 106 copies/ml, specific cultures inoculated a posteriori were positive for U. urealyticum. Levofloxacin and azithromycine antibiotherapy was initiated. Susceptibility testing showed an intermediate sensibility to ciprofloxacin and clarithromycin. The strain was susceptible to doxycycline. Following cessation of breastfeeding, we started antibiotic treatment with doxycycline for 4 weeks. The subsequent course was favorable with an excellent functional and biological outcome.

Conclusions

We report the first case of septic arthritis due to U. urealyticum after caesarean section. We hypothesize that the breach of the genital mucosal barrier during the caesarean section led to hematogenous spread resulting in purulent septic arthritis. The initial beta-lactam based antibiotic treatment, initiated for a purulent arthritis, did not provide coverage for cell wall deficient organisms. Detection of 16S rRNA allowed for a correct microbiological diagnosis in a patient with an unexpected clinical course.
Concurrent acute myositis and Guillain-Barre syndrome in Cytomegalovirus infection – a rare case report
Authors: Sakthivadivel Varatharajan , Naveenraj Palanisamy , Kachhwaha Arjun , Kumar Deepak , Anne Puneeth Babu , Elhence Poonam , Meena Mahadev
Published: October 2020

Background

Cytomegalovirus (CMV) is a double stranded DNA virus and ubiquitous in nature. Association of Guillain-Barre syndrome (GBS) and CMV is well known but CMV acute myositis is a rare condition. Restriction of movements of limbs due to severe pain in myositis may obscure the diagnosis of GBS and this may easily miss.

Case presentation

Here we describe a 29-year-old male presenting with pain and swelling of bilateral lower limbs which progressed rapidly with increasing serum creatine kinase levels with positive IgM CMV antibodies. In view of no improvement in clinical condition, patient was further evaluated and found to have concurrent GBS. He was treated with plasmapheresis and improved.

Conclusion

Cytomegalovirus infection presenting as acute myositis is a uncommon and further association with GBS is a rare occurrence.