bluuebunny/crossref_metadata_2025_split huggingface dataset:
T-cell lymphoma secondary to checkpoint inhibitor therapy
Authors: Anand Kartik , Ensor Joe , Pingali Sai Ravi , Hwu Patrick , Duvic Madeleine , Chiang Stephen , Miranda Roberto , Zu Youli , Iyer Swaminathan 
Published: February 2020

BackgroundMurine model suggests programmed cell death-1 (PD-1), an immune checkpoint not only plays role in tumor escape but is also a tumor suppressor for T-cells. But until, no reports of secondary T-cell lymphoma postuse of immune checkpoint inhibitors (ICIs) has been reported. Herein, we present a hitherto unreported phenomenon of secondary T-cell lymphoma when PD-1 inhibitor was used in a patient diagnosed with a tumor of epithelial origin.Case reportA man in mid-70s presented with biopsy-proven metastatic tumor of epithelial origin. Patient received carboplatin in combination with paclitaxel for four cycles leading to partial remission. The patient was subsequently switched to pembrolizumab due to persistent disease in the mediastinum. After four cycles of PD-1 inhibitor, patient presented with progression of disease and was diagnosed with biopsy-proven peripheral T-cell lymphoma-not otherwise specified. Based on the reported tumor suppressor function of PD-1 in murine models, we hypothesized that the use of PD-1 inhibitor caused clonal proliferation of abnormal T-cell clone leading to T-cell lymphoma. T-cell receptor (TCR) sequencing was performed by TCRβ sequencing and T-cell clones from pre-ICI treatment specimen were compared with post-ICI treatment specimens. We show that one of the T-cell clones present in pre-ICI treatment specimen at a low frequency of had massive expansion to become most dominant clone in post-ICI treatment specimens leading to lymphoma. Moreover, targeted exome sequencing revealed a new TET2 mutation in the clone representing the lymphoma.Next, we retrospectively reviewed the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS), the pharmacovigilance database from 2012 to 2018 to find the reported incidence of this phenomenon and calculated the reporting OR (ROR) for disproportionality analysis for risk of T-cell lymphoma due to checkpoint inhibitors compared with other drugs. In FAERS, the incidence of T-cell lymphoma post-ICIs (pembrolizumab, nivolumab and ipilimumab) was found to be 0.02% with 17% mortality. The ROR probability of risk of T-cell lymphoma compared with other drugs in pharmacovigilance database was increased at 1.91.ConclusionsT-cell lymphoma is a rare sequela of ICIs with high mortality. Larger studies with long-term follow-up of patients receiving ICIs is needed.
Salvage ipilimumab associated with a significant response in sarcomatoid renal cell carcinoma
Authors: George Gemlyn , Schmidt Laura , Tolat Parag , Riese Mathew , Kilari Deepak 
Published: February 2020

BackgroundMetastatic sarcomatoid renal cell carcinoma (sRCC) is an aggressive variant of RCC with generally poor prognosis. Treatment with vascular endothelial growth factor inhibitors or chemotherapy generates only short-lived responses. Recent research has suggested a role for combination checkpoint inhibition as first line treatment for metastatic sRCC. This therapy consists of induction with cytotoxic T-lymphocyte-associated protein 4 inhibitor, ipilimumab, administered with programmed cell death protein 1 (PD-1) inhibitor, nivolumab. After completion of four cycles of combination therapy, single-agent maintenance nivolumab is recommended until progression. Patients who progress on maintenance nivolumab are switched to alternate therapy. Herein, we present a case of a patient with RCC who progressed on maintenance nivolumab who, on retreatment with ipilimumab, demonstrated a significant response In addition, we summarize important findings to support the role of salvage ipilimumab in patients with sRCC.Case presentationA 46-year-old man presented with flank pain and hematuria, the work up of which noted a left kidney mass for which he underwent nephrectomy and was diagnosed with localized sRCC with 60% sarcomatoid differentiation. Within 3 months of nephrectomy, he presented with recurrent flank pain and was diagnosed with recurrence of disease. He was treated with ipilimumab 1 mg/kg and nivolumab 3 mg/kg for four doses and demonstrated a partial response. He was then transitioned to single agent nivolumab maintenance. After 3 months on maintenance therapy, he was noted to have progression of disease. Given prior response to immune check point combination, it was decided to rechallenge the patient with 1 mg/kg ipilimumab. After two doses of ipilimumab and nivolumab combination therapy, the patient was noted to have a partial response. He maintained a response for an additional 9 months and treatment was eventually discontinued due to grade 3 toxicity and progression.ConclusionsThis case report demonstrates the utility of retreatment with ipilimumab as a salvage option for patients progressing on maintenance PD-1 inhibitors in metastatic RCC. Further studies are needed to identify predictors of response and toxicity to this approach, as well as the optimal scheduling of ipilimumab with maintenance nivolumab.
Randomized phase II study of the Bruton tyrosine kinase inhibitor acalabrutinib, alone or with pembrolizumab in patients with advanced pancreatic cancer
Authors: Overman Michael , Javle Milind , Davis Richard E , Vats Pankaj , Kumar-Sinha Chandan , Xiao Lianchun , Mettu Niharika B , Parra Edwin R , Benson Al B , Lopez Charles D , Munugalavadla Veerendra , Patel Priti , Tao Lin , Neelapu Sattva , Maitra Anirban 
Published: February 2020

BackgroundThe immunosuppressive desmoplastic stroma of pancreatic cancer represents a major hurdle to developing an effective immune response. Preclinical studies in pancreatic cancer have demonstrated promising anti-tumor activity with Bruton tyrosine kinase (BTK) inhibition combined with programmed cell death receptor-1 (PD-1) blockade.MethodsThis was a phase II, multicenter, open-label, randomized (1:1) clinical trial evaluating the BTK inhibitor acalabrutinib, alone (monotherapy) or in combination with the anti-PD-1 antibody pembrolizumab (combination therapy). Eligible patients were adults with histologically confirmed metastatic or locally advanced unresectable pancreatic ductal adenocarcinoma with an Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤1 who had received at least one prior systemic therapy. Oral acalabrutinib 100 mg twice daily was administered with or without intravenous pembrolizumab 200 mg on day 1 of each 3-week cycle. Peripheral blood was analyzed for changes in immune markers, and tumors from exceptional responders were molecularly analyzed.ResultsA total of 77 patients were enrolled (37 monotherapy; 40 combination therapy) with a median age of 64 years; 77% had an ECOG PS of 1. The median number of prior therapies was 3 (range 1–6). Grade 3–4 treatment-related adverse events were seen in 14.3% of patients in the monotherapy arm and 15.8% of those in the combination therapy arm. The overall response rate and disease control rate were 0% and 14.3% with monotherapy and 7.9% and 21.1% with combination therapy, respectively. Median progression-free survival was 1.4 months in both arms. Peripheral blood flow analysis demonstrated consistent reductions in granulocytic (CD15+) myeloid-derived suppressor cells (MDSCs) over time. Two exceptional responders were found to be microsatellite stable with low tumor mutation burden, low neoantigen load and no defects in the homologous DNA repair pathway.ConclusionsThe combination of acalabrutinib and pembrolizumab was well tolerated, but limited clinical activity was seen with either acalabrutinib monotherapy or combination therapy. Peripheral reductions in MDSCs were seen. Efforts to understand and target the pancreatic tumor microenvironment should continue.Trial registration numberNCT02362048.
Deficient serum furin predicts risk of abdominal obesity: findings from a prospective cohort of Chinese adults
Authors: He Yan , Ren Liyun , Zhang Qiu , Zhang Mingzhi , Shi Jijun , Hu Weidong , Peng Hao 
Published: February 2020

ABSTRACTBackgroundAs a key enzyme of natriuretic peptides system playing an integral role in energy homeostasis, furin may be a potential contributor to obesity. However, the association between furin and obesity has been scarcely studied. This study aims to examine the prospective association between serum furin and abdominal obesity.MethodsWaist circumference (WC) was measured twice 4 years apart for a total of 892 Chinese adults free of abdominal obesity at baseline. Abdominal obesity was defined as WC over 85 cm for men and as WC over 80 cm for women. A Cox proportional hazard model was constructed to examine the association of baseline serum furin with incident abdominal obesity.ResultsAfter an average 4 years of follow-up, 184 participants developed new abdominal obesity. Baseline serum furin was significantly associated with dynamic body weight during follow-up (β=−0.593, p=0.003). Participants with a higher level of serum furin at baseline were less likely to develop new abdominal obesity compared with those with a lower level of serum furin (HR=0.81, 95% CI 0.67 to 0.97).ConclusionsA lower level of serum furin predicts a higher risk of developing future abdominal obesity in Chinese adults. Furin deficiency may be a contributor to abdominal obesity but still needs further investigations.
H2FPEF score predicts 1-year rehospitalisation of patients with heart failure with preserved ejection fraction
Authors: Tao Yifei , Wang Wenjing , Zhu Jing , You Tao , Li Yi , Zhou Xiang 
Published: February 2020

ABSTRACTBackgroundHeart failure with preserved ejection fraction (HFpEF) has received widespread attention in recent years. There is currently a lack of valuable predictors for the prognosis of this disease. Here, we aimed to identify a non-invasive scoring system that can effectively predict 1-year rehospitalisation for patients with HFpEF.MethodsWe included 151 consecutive patients with HFpEF in a prospective cohort study and investigated the association between H2FPEF score and 1-year readmission for heart failure using multivariate Cox regression analysis.ResultsOur findings indicated that obesity, age &gt;70 years, treatment with ≥2 antihypertensives, echocardiographic E/e’ ratio &gt;9 and pulmonary artery pressure &gt;35 mm Hg were independent predictors of 1-year readmission. Three models (support vector machine, decision tree in R and Cox regression analysis) proved that H2FPEF score could effectively predict 1-year readmission for patients with HFpEF (area under the curve, 0.910, 0.899 and 0.771, respectively; p&lt;0.001).ConclusionOur study demonstrates that the H2FPEF score has excellent predictive value for 1-year rehospitalisation of patients with HFpEF.
Analysis of judicial precedent cases regarding epidural injection in chronic pain management in Republic of Korea
Authors: Cho Soo Ick , Shin SuHwan , Jung Haesun , Moon Jee Youn , Lee Ho-Jin 
Published: February 2020

BackgroundAlthough there is a low incidence of complications associated with epidural injections, pain physicians should still remain vigilant for potentially serious adverse outcomes. This study aimed to identify and describe the major complications of epidural injections.MethodsThis retrospective, observational, medicolegal study analyzed closed cases of precedents involving complications of epidural injections from January 1997 to August 2019 using the database of the Supreme Court of Korea’s judgement system. Clinical characteristics and judgement statuses were analyzed.ResultsOf the 73 potential cases assessed for eligibility, a total of 49 malpractice cases were included in the final analysis. Thirty-three claims resulted in payments to the plaintiffs, with a median payment of US$103 828 (IQR: US$45 291–US$265 341). The most common complication was infection (n=13, 26.5%), followed by worsening pain (n=8, 16.3%). Physician malpractice before, during, and after the procedure was claimed by plaintiffs in 18 (36.7%), 44 (89.8%), and 31 (63.3%) cases, respectively. Of these cases, 6 (33.3%), 19 (43.2%), and 15 (48.4%), respectively, were adjudicated in favor of the plaintiffs by the courts. In cases involving postprocedural physician errors, the majority (13/15) of the plaintiff verdicts were related to delayed management. Violation of the physician’s duty of informed consent was claimed by plaintiffs in 31 (63.3%) cases, and 14 (45.2%) of these cases were judged medical malpractice.ConclusionsOur data will allow pain physicians to become acquainted with the major epidural injection-associated complications that underlie malpractice cases.
Phase structures and transitions of Born–Infeld black holes in a grand canonical ensemble
Authors: Liang Kangkai , Wang Peng , Wu Houwen , Yang Mingtao 
Published: February 2020

AbstractTo make a Born–Infeld (BI) black hole thermally stable, we consider two types of boundary conditions, i.e., the asymptotically anti-de Sitter (AdS) space and a Dirichlet wall placed in the asymptotically flat space. The phase structures and transitions of these two types of BI black holes, namely BI-AdS black holes and BI black holes in a cavity, are investigated in a grand canonical ensemble, where the temperature and the potential are fixed. For BI-AdS black holes, the globally stable phases can be the thermal AdS space. For small values of the potential, there is a Hawking-Page-like first order phase transition between the BI-AdS black holes and the thermal-AdS space. However, the phase transition becomes zeroth order when the values of the potential are large enough. For BI black holes in a cavity, the globally stable phases can be a naked singularity or an extremal black hole with the horizon merging with the wall, which both are on the boundaries of the physical parameter region. The thermal flat space is never globally preferred. Besides a first order phase transition, there is a second order phase transition between the globally stable phases. Thus, it shows that the phase structures and transitions of BI black holes with these two different boundary conditions have several dissimilarities.
Paid Companions: Human-Nonhuman Animal Relations in Japanese Animal Cafés
Authors: Robinson Amanda S. 
Published: February 2020

Abstract
Animal cafés, a type of business where customers pay by the hour to spend time relaxing with nonhuman animals and other animal lovers, became popular in Japan during the late 2000s as part of the iyashi, or healing, boom. Young Japanese customers in need of positive affective experiences to address feelings, economic and social precarity turn to businesses like these to meet their emotional needs, engaging socially with animals in a commodified space. This article explores the kinds of intimate bonds that are created between the human customer and animal “staff” in these contexts, where customers engage with animals on their own terms, enjoying their companionship without any long-term responsibility for their care, and the effect this has on the lives of the café animals.
The Convention on the Legal Status of the Caspian Sea: The Final Answer or an Interim Solution to the Caspian Question?
Authors: Karataeva Elena 
Published: February 2020

Abstract
This article analyses new developments in the question of the Caspian Sea legal status, namely the signing of the Convention on the Legal Status of the Caspian Sea on 12 August 2018 in Kazakhstan, after twenty-six years in the making. First, the article provides an overview of the history of the Caspian Sea ownership and examines the legal status question from the collapse of the USSR to the present day. Then, the text of the newly signed Convention is examined to determine whether it provides the final answers to the issues of the legal status and delimitation of the sea. It is contended that despite this seminal breakthrough, the convention does not provide a complete solution. Specifically, while it establishes Caspian Sea zones and their limits, it fails to clarify some key contentious aspects, including delimitation principles between the opposite and adjacent Caspian States, which remain to be determined bilaterally.
Archetypal Origins
Authors: Goodwyn Erik 
Published: February 2020

Abstract
The question of whether or not archetypes are transmitted biologically or culturally is wrongly posed and has hampered progress in Jungian thought regarding archetype theory. Considerations regarding psychological development show that some contents of the human psyche are, strictly speaking, neither biologically nor culturally derived. Examples are given, and the question becomes, How does this fact affect archetype theory? The present essay examines this question in depth.
Children’s learning from a Smokefree Sports programme: Implications for health education
Authors: Fairbrother Hannah , Curtis Penny , Kirkcaldy Andrew 
Published: February 2020

Objective: This article reports on a qualitative evaluation of the Love Life, Smokefree Sports primary school pilot intervention. This 8-week programme used sports and physical activity sessions to convey Smokefree messages to 120 children aged 10 and 11 in two primary schools in Sheffield in 2018. The study aimed to understand children’s experiences of participating in the programme. Its objectives were to explore children’s recall of the health promotion messages associated with each of the learning sessions; explore children’s perceptions of the meaningfulness of those messages in the context of their everyday lives; and identify and understand any contextual factors that might impact upon children’s recall and/or the meaningfulness of the Smokefree messages. Method: Qualitative data were generated with 25 children through focus groups after the programme concluded. Data were analysed thematically using cross-sectional, categorical indexing. Results: Learning from the programme was particularly likely to be described as meaningful by children when they could interact with material and visual representations of complex ideas and when sessions involved strongly embodied experiences. However, children did not always find it easy to relate learning to their everyday lives and sometimes struggled to reconcile pre-existing, contextualised understandings with intervention messages. We mobilise the concept of critical health literacy as a theoretical lens through which to interpret these findings. Conclusion: Health education should be meaningful in the context of children’s everyday lives. Starting from the premise that children are active critical health literacy practitioners and working with them to design and evaluate health education initiatives can promote this.
Psychotic experiences and psychiatric treatment utilization in Buenos Aires
Authors: Oh Hans , Koyanagi Ai , DeVylder Jordan E , Leiderman Eduardo A 
Published: February 2020

Objective: Psychotic experiences are associated with psychiatric treatment utilization, though findings have not been entirely consistent. Furthermore, it is unclear how psychotic experiences relate to specific types of psychiatric treatment, and whether mental illness moderates these associations. Methods: In total, 1,036 adult residents of Buenos Aires were recruited through convenience sampling in public places. Multivariable logistic regression models examined the associations between psychotic experiences and psychiatric treatment, adjusted for age, sex and education. Analyses were then stratified by diagnosis of mental illness. Results: Approximately 17.95% ( N = 186) of the sample reported at least one psychotic experience over the past week, about 22.39% ( N = 232) of the sample was receiving some psychiatric or psychological treatment and 8.59% ( N = 89) was receiving psychopharmacological treatment. In the total sample, psychotic experiences were associated with greater odds of being in psychiatric/psychological treatment (adjusted odds ratio (AOR): 1.52; 95% confidence interval (CI): 1.05–2.21) and psychopharmacological treatment (AOR: 2.49; 95% CI: 1.52–4.09), adjusted for age, sex and education. Mental illness did not moderate the association between psychotic experiences and psychiatric/psychological treatment, but did moderate the association between psychotic experiences and psychopharmacological treatment. Among people with mental disorders, psychotic experiences were associated with greater odds of receiving psychopharmacological treatment (AOR: 14.63; 95% CI: 1.73–123.45) versus people without mental disorders (AOR: 1.75; 95% CI: 0.98–3.15). Conclusion: Psychotic experiences are associated with psychiatric treatment utilization, particularly psychopharmacological treatment among people with a co-occurring mental illnesses. Translational research should explore the utility of psychosis screens in assessing need for medication or clinical responsiveness to medications.
Patient-reported experience and outcomes from orthodontic treatment
Authors: Bradley Elizabeth , Shelton Andrew , Hodge Trevor , Morris David , Bekker Hilary , Fletcher Steven , Barber Sophy 
Published: February 2020

Objective: To measure patient-reported impact of orthodontic treatment in terms of pre-treatment concerns, treatment experience and treatment outcome. Setting: Four sites in Yorkshire, including two secondary care settings (Leeds Dental Institute and St Luke’s Hospital, Bradford) and two specialist orthodontic practices. Design: Cross-sectional survey. Participants: NHS orthodontic patients (aged 12+ years) who have completed comprehensive orthodontic treatment, excluding orthognathic surgery and craniofacial anomalies. Methods: Participants were opportunistically identified by the direct clinical care team during scheduled appointments and those eligible were invited to participate. Data were collected using the Orthodontic Patient Treatment Impact Questionnaire (OPTIQ), a validated 12-item measure with questions relating to pre-treatment experience, impact of treatment and outcome from treatment. Results: Completed questionnaires for analysis included 120 from primary care and 83 from secondary care. The most common pre-treatment concerns were alignment (89%) and being embarrassed to smile (63%). The most common expectations from orthodontic treatment were improved confidence to eat (87%) and smile (72%) in front of others, improved appearance of teeth (85%) and reduced teasing/bullying (63%). Only 67% respondents recalled receiving written information and the lowest recall related to retainer type and length of retention. The most commonly reported complications were sore mouth (68%), fixed appliance breakage (61%) and gingivitis (39%). Treatment caused greatest impact in relation to pain, limitations in eating and effect on speech. Overall satisfaction with orthodontic treatment was reported by 96% of respondents, 87% would have orthodontic treatment again (if needed) and 91% would recommend treatment to a friend. Conclusions: The OPTIQ is a useful patient-reported tool to identify pre-treatment concerns and expectations, treatment experience and outcome. Orthodontic treatment leads to high levels of satisfaction.