bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elucidation of Pelareorep Pharmacodynamics in A Phase I Trial in Patients with KRAS-Mutated Colorectal Cancer
Authors: Goel Sanjay , Ocean Allyson J. , Parakrama Ruwan Y. , Ghalib Mohammad H. , Chaudhary Imran , Shah Umang , Viswanathan Sengottuvel , Kharkwal Himanshu , Coffey Matthew , Maitra Radhashree 
Published: March 2020

Abstract
KRAS mutation is a negative predictive biomarker of anti-EGFR agents in patients with metastatic colorectal cancer (mCRC), and remains an elusive target. Pelareorep, a double-stranded RNA virus selectively replicates in KRAS-mutated cells, and is synergistic with irinotecan. A dose escalation trial of FOLFIRI/bevacizumab [irinotecan (150–180 mg/m2) and pelareorep (1 × 1010 TCID50–3 × 1010 TCID50)] was implemented in adult patients with oxaliplatin refractory/intolerant, KRAS-mutant mCRC. Pelareorep was administered intravenously over 1 hour on days 1–5 every 4 weeks. Additional studies included pharmacokinetics, tumor morphology, and immune responses. Among FOLFIRI-naïve patients, the highest dose of FOLFIRI/bevacizumab (180 mg/m2 irinotecan) and pelareorep (3 × 1010 TCID50) was well tolerated, without a dose-limiting toxicity. At the recommended phase II dose, 3 of 6 patients (50%) had a partial response; the median progression-free and overall survival (PFS, OS) were 65.6 weeks and 25.1 months, respectively. Toxicities included myelosuppression, fatigue, and diarrhea. Transmission electron microscopy revealed viral factories (viral collections forming vesicular structures), at various stages of development. Immunogold staining against viral capsid σ-1 protein demonstrated viral “homing” in the tumor cells. The nucleus displayed sufficient euchromatin regions suggestive of active transcription. Flow cytometry revealed rapid dendritic cell maturation (48 hours) with subsequent activation of cytotoxic T cells (7 days). The combination of pelareorep with FOLFIRI/bevacizumab is safe. The PFS and OS data are encouraging and deserve further exploration. Pelareorep leads to a clear recurrent immune stimulatory response with cytotoxic T-cell activation, and homes and replicates in the tumor.
The Authenticity of Paracelsus’ Astronomia Magna and Brief an die Wittenberger Theologen: Towards a Diagnostic Rubric Clarifying Authentic and Spurious Elements in Paracelsus’ Oeuvre on the Basis of Theological Motifs
Authors: Daniel Dane T. 
Published: March 2020

Abstract
The paper is an evaluation of differing opinions regarding the authenticity of two of Paracelsus’ works, the Astronomia Magna (1537/1538) and Brief an die Wittenberger Theologen (1525). Karl Sudhoff – the exceptionally erudite and prolific Paracelsus scholar and editor – considered Paracelsus’ letter to Luther and the Wittenberg theologians to be spurious. Others have questioned the extent to which the Astronomia Magna (often considered to be Paracelsus’ Meisterstück) should be placed among the genuine texts of the Paracelsian corpus. Based on historical and conceptual data, and focusing on Paracelsus’ theology, the author argues that both works under consideration are authentic. The study thus highlights the need to develop a diagnostic rubric for evaluating the authenticity of works in the Paracelsian oeuvre and suggests ideas toward this end on the basis of theological motifs prevalent within Paracelsus’ clearly authentic works.
The Astronomia Olympi novi and the Theologia Cabalistica: Two Pseudo-Paracelsian Works of the Philosophia Mystica (1618)
Authors: Žemla Martin 
Published: March 2020

Abstract
The Astronomia Olympi novi and the Theologia Cabalistica were published as part of the Philosophia Mystica (1618). This influential collection of Paracelsian and Weigelian texts was among the first to include a publication of the theologica of Paracelsus. Both of these short pseudo-Paracelsian works were written by Adam Haslmayr (1560-1630), the propagator of the “Theophrastia Sancta,” a philosophical theology of Paracelsus mixed with Weigelian and alchemical influences. These works, taken in the Philosophia Mystica, are among the very few of his texts that appeared in print in his lifetime. In this paper, the content of both pseudepigrapha is analyzed and related to ideas found in both the authentic and the pseudepigraphic works of Paracelsus, as well as in relevant works of some Paracelsians (Khunrath, Figulus, Weigel, Croll, Siebmacher and Mögling). Specifically, the notions of the “Olympus novus” and the “cabalistic principles” are discussed in a wider context.
Writing Genocide
Authors: Becker Heike 
Published: March 2020

Abstract
In this article I read several recently published novels that attempt to write the early 20th century Namibian experience of colonial war and genocide. Mari Serebrov’s Mama Namibia, Lauri Kubuitsile’s The Scattering and Jaspar Utley’s The Lie of the Land set out to write the genocide and its aftermath. Serebrov and Kubuitsile do so expressly from the perspective of survivors; their main characters are young Herero women who live through war and genocide. This sets Mama Namibia and The Scattering apart from the earlier literature, which—despite an enormous divergence of political and aesthetic outlooks—tended to be written from the perspective of German male protagonists. The Lie of the Land, too, scores new territory in postcolonial literature. I read these recent works of fiction against an oral history-based biography, in which a Namibian author, Uazuvara Katjivena, narrates the story of his grandmother who survived the genocide.
Namibian Life Stories from the ‘Struggle Days’
Authors: Malaba Mbongeni Zikhethele 
Published: March 2020

Abstract
This article analyses representative life stories that reflect the experiences of people who participated in the Namibian liberation struggle, as well as one narrative that reflects the traumatic effect of the brutal murder of her mother witnessed by a five year old girl. The stories detail the vicious nature of settler colonialism in South West Africa and the motive that drove youths to abscond from school to join SWAPO camps in neighbouring countries. Two of the male authored texts focus on the political dimensions of the struggle, with minimal personal details; the two accounts penned by women who obtained secondary and tertiary education in exile and underwent military training foreground the personal dimension that is understated in the male accounts. The human side of war, suffering and discrimination is captured in all the accounts, in differing degrees. The strong Christian beliefs of the selected authors are a striking feature in most of the life stories.
Extremely Early Summer Monsoon Onset in the South China Sea in 2019 Following an El Niño Event
Authors: Hu Peng , Chen Wen , Chen Shangfeng , Liu Yuyun , Huang Ruping 
Published: March 2020

AbstractThe El Niño–Southern Oscillation (ENSO) is regarded as one of the most important factors for onset of the South China Sea summer monsoon (SCSSM). Previous studies generally indicated that an El Niño event tends to result in a late onset of the SCSSM monsoon. However, this relationship has not been true in recent years, particularly when an extremely early SCSSM onset (1 May 2019) occurred following the 2018/19 El Niño event in the preceding winter. The processes of the second earliest SCSSM onset in the past 41 years were investigated using NCEP–DOE reanalysis, OLR data, and ERSST. A negative sea surface temperature and associated anticyclonic anomalies were absent over the western North Pacific in the late spring of 2019 following an El Niño event in the preceding winter. Thus, the mean circulation in the late spring of 2019 does not prevent SCSSM onset, which is in sharp contrast to the composited spring of the El Niño decaying years. The convective active and westerly phases of a 30–60-day oscillation originating from the Indian Ocean provided a favorable background for the SCSSM onset in 2019. In addition, the monsoon onset vortex over the Bay of Bengal and the cold front associated with a midlatitude trough over East Asia also played important roles in triggering the early onset of the SCSSM in 2019. No tropical cyclone appeared over the western North Pacific during April and May, and the enhancement of quasi-biweekly oscillation mainly occurs after the SCSSM onset; thus, these two factors contribute little to the SCSSM onset in 2019.
Patient Perception and Duration of Pain after Microdirect Laryngoscopy
Authors: Tsang Trylon Matthew , Brett Oliver , Hu Amanda 
Published: March 2020

ObjectivePostoperative pain is an important part of the patient’s surgical experience. The objective was to evaluate patient perception and duration of pain after microdirect laryngoscopy (MDL).Study DesignCase series with planned data collection.SettingTertiary care, academic center.Subjects and MethodsAdult patients undergoing MDL were administered the short‐form McGill Pain Questionnaire (SF‐MPQ) before surgery and on postoperative days (PODs) 1, 3, and 7. Demographic and clinical data were collected.ResultsIn total, 130 patients (mean age 52.6 years, 84 male) participated in the study. About 46.2% required analgesia on POD 1, but only 23.1% required opioids. Overall, mild levels of pain were reported on the SF‐MPQ: sensory score, affective score, total score, present pain intensity (PPI), and visual analog scale (VAS). Patients reported a significant increase in pain on POD 1, with decreases in pain on PODs 3 and 7. Pain score returned to preoperative values for total score and affective score on POD 7 but remained significantly elevated for PPI, VAS, and sensory score. None of the following factors were associated with increased pain: age, sex, body mass index, Mallampati score, Cormack score, laryngoscope used, type of MDL, time under anesthesia, employment status, intubation, Voice Handicap Index 10, and chronic pain history.ConclusionAlthough mild levels of pain were reported after MDL, the pain persisted for up to 7 days. No demographic or clinical factors were found to be associated with increased pain. This study was one of the few prospective studies evaluating pain after MDL.
Hearing Loss, Loneliness, and Social Isolation: A Systematic Review
Authors: Shukla Aishwarya , Harper Michael , Pedersen Emily , Goman Adele , Suen Jonathan J. , Price Carrie , Applebaum Jeremy , Hoyer Matthew , Lin Frank R. , Reed Nicholas S. 
Published: March 2020

ObjectiveSocial isolation and loneliness are associated with increased mortality and higher health care spending in older adults. Hearing loss is a common condition in older adults and impairs communication and social interactions. The objective of this review is to summarize the current state of the literature exploring the association between hearing loss and social isolation and/or loneliness.Data SourcesPubMed, Embase, CINAHL Plus, PsycINFO, and the Cochrane Library.Review MethodsArticles were screened for inclusion by 2 independent reviewers, with a third reviewer for adjudication. English‐language studies of older adults with hearing loss that used a validated measure of social isolation or loneliness were included. A modified Newcastle‐Ottawa Scale was used to assess the quality of the studies included in the review.ResultsOf the 2495 identified studies, 14 were included in the review. Most of the studies (12/14) were cross‐sectional. Despite the heterogeneity of assessment methods for hearing status (self‐report or objective audiometry), loneliness, and social isolation, most multivariable‐adjusted studies found that hearing loss was associated with higher risk of loneliness and social isolation. Several studies found an effect modification of gender such that among women, hearing loss was more strongly associated with loneliness and social isolation than among men.ConclusionsOur findings that hearing loss is associated with loneliness and social isolation have important implications for the cognitive and psychosocial health of older adults. Future studies should investigate whether treating hearing loss can decrease loneliness and social isolation in older adults.
Clinical vs Microscopic Extranodal Extension and Survival in Oropharyngeal Carcinoma in the Human Papillomavirus Era
Authors: Gal Thomas J. , O’Brien Kaitlin July , Chen Quan , Huang Bin 
Published: March 2020

ObjectiveExtranodal extension (ENE) is known to be associated with poor outcomes in head and neck squamous cell carcinoma. The objective of this study is to examine the impact of extent of ENE on survival in oropharyngeal carcinoma in the human papillomavirus (HPV) era.Study DesignRetrospective database review.SettingReview of the National Cancer Database.Subjects and MethodsThe National Cancer Database was used to examine surgically treated head and neck squamous cell carcinoma of the tonsil and base of tongue from 2010 to 2015. Nodes available for pathologic examination were classified as ENE negative (–), ENE clinically (+), or ENE (+) on pathology only. The primary outcome was overall survival. Cox regression modeling was used to examine the effect of ENE on survival while controlling for patient demographics, HPV status, stage, adjuvant radiation, and chemotherapy.ResultsOf the 66,106 patients identified, 16,845 were treated with surgery ± adjuvant therapy, 8780 of whom were known HPV+. Overall 5‐year survival for this group was 86%. Documented ENE was associated with over a 60% decrease in survival for clinical (hazard ratio [HR], 1.63) and pathologic (HR, 1.62) ENE compared to negative ENE, after adjustment for stage, adjuvant radiation ± chemotherapy, HPV, and other variables. No significant differences were found between clinical and pathologic ENE (HR, 1.001).ConclusionWhile both surgically resected clinical and pathologic ENE are associated with decreased survival, no significant differences are observed between the two. The impact of these observations on potential de‐escalation therapeutic strategies requires further study.
Palliative care and infection management at end of life in nursing homes: A descriptive survey
Authors: Tark Aluem , Estrada Leah V , Tresgallo Mary E , Quigley Denise D , Stone Patricia W , Agarwal Mansi 
Published: March 2020

Background: Infections are common occurrences at end of life that are associated with high rates of morbidity and mortality among frail elderly individuals. The problem of infections in nursing homes has led to a subsequent overuse and misuse of antibiotics in this already-frail population. Improving palliative care in nursing homes has been proposed as a key strategy to reduce the use of antibiotics. Aim: The aim of this study was to describe the current status of how nursing homes integrates palliative care and infection management at end of life across the nation. Design: This is a cross-sectional survey of nationally representative US nursing homes. Setting/participants: Between November 2017 and October 2018, a survey was conducted with a nationally representative random sample of nursing homes and 892 surveys were completed (49% response rate). The weighted study sample represented 15,381 nursing homes across the nation. Results: Most nursing homes engaged in care plan documentation on what is important to residents (90.43%) and discussed spiritual needs of terminally ill residents (89.50%). In the event of aspiration pneumonia in terminally ill residents, 59.43% of nursing homes responded that resident would be transferred to the hospital. In suspected urinary tract infection among terminally ill residents, 66.62% of nursing homes responded that the resident will be treated with antibiotics. Conclusion: The study found wide variations in nursing home palliative care practices, particularly for timing of end-of-life care discussions, and suboptimal care reported for antibiotic usage. Further education for nursing home staff on appropriate antibiotic usage and best practices to integrate infection management in palliative care at the end of life is needed.
Intercostal vessel screening prior to pleural interventions by the respiratory physician: a prospective study of real world practice
Authors: Bedawi Eihab O. , Talwar Ambika , Hassan Maged , McCracken David J. , Asciak Rachelle , Mercer Rachel M. , Kanellakis Nikolaos I. , Gleeson Fergus V. , Hallifax Rob J. , Wrightson John M. , Rahman Najib M. 
Published: March 2020

IntroductionThe rising incidence of pleural disease is seeing an international growth of pleural services, with physicians performing an ever-increasing volume of pleural interventions. These are frequently conducted at sites without immediate access to thoracic surgery or interventional radiology and serious complications such as pleural bleeding are likely to be under-reported.AimTo assess whether intercostal vessel screening can be performed by respiratory physicians at the time of pleural intervention, as an additional step that could potentially enhance safe practice.MethodsThis was a prospective, observational study of 596 ultrasound-guided pleural procedures conducted by respiratory physicians and trainees in a tertiary centre. Operators did not have additional formal radiology training. Intercostal vessel screening was performed using a low frequency probe and the colour Doppler feature.ResultsThe intercostal vessels were screened in 95% of procedures and the intercostal artery (ICA) was successfully identified in 53% of cases. Screening resulted in an overall site alteration rate of 16% in all procedures, which increased to 30% when the ICA was successfully identified. This resulted in procedure abandonment in 2% of cases due to absence of a suitable entry site. Intercostal vessel screening was shown to be of particular value in the context of image-guided pleural biopsy.ConclusionIntercostal vessel screening is a simple and potentially important additional step that can be performed by respiratory physicians at the time of pleural intervention without advanced ultrasound expertise. Whether the widespread use of this technique can improve safety requires further evaluation in a multi-centre setting with a robust prospective study.
Mepolizumab effectiveness and identification of super-responders in severe asthma
Authors: Harvey Erin S. , Langton David , Katelaris Constance , Stevens Sean , Farah Claude S. , Gillman Andrew , Harrington John , Hew Mark , Kritikos Vicky , Radhakrishna Naghmeh , Bardin Philip , Peters Matthew , Reynolds Paul N. , Upham John W. , Baraket Melissa , Bowler Simon , Bowden Jeffrey , Chien Jimmy , Chung Li Ping , Grainge Christopher , Jenkins Christine , Katsoulotos Gregory P. , Lee Joy , McDonald Vanessa M. , Reddel Helen K. , Rimmer Janet , Wark Peter A.B. , Gibson Peter G. 
Published: March 2020

Severe asthma is a high-burden disease. Real-world data on mepolizumab in patients with severe eosinophilic asthma is needed to assess whether the data from randomised controlled trials are applicable in a broader population.The Australian Mepolizumab Registry (AMR) was established with an aim to assess the use, effectiveness and safety of mepolizumab for severe eosinophilic asthma in Australia.Patients (n=309) with severe eosinophilic asthma (median age 60 years, 58% female) commenced mepolizumab. They had poor symptom control (median Asthma Control Questionnaire (ACQ)-5 score of 3.4), frequent exacerbations (median three courses of oral corticosteroids (OCS) in the previous 12 months), and 47% required daily OCS. Median baseline peripheral blood eosinophil level was 590 cells·µL−1. Comorbidities were common: allergic rhinitis 63%, gastro-oesophageal reflux disease 52%, obesity 46%, nasal polyps 34%.Mepolizumab treatment reduced exacerbations requiring OCS compared with the previous year (annualised rate ratio 0.34 (95% CI 0.29–0.41); p<0.001) and hospitalisations (rate ratio 0.46 (95% CI 0.33–0.63); p<0.001). Treatment improved symptom control (median ACQ-5 reduced by 2.0 at 6 months), quality of life and lung function. Higher blood eosinophil levels (p=0.003) and later age of asthma onset (p=0.028) predicted a better ACQ-5 response to mepolizumab, whilst being male (p=0.031) or having body mass index ≥30 (p=0.043) predicted a lesser response. Super-responders (upper 25% of ACQ-5 responders, n=61, 24%) had a higher T2 disease burden and fewer comorbidities at baseline.Mepolizumab therapy effectively reduces the significant and long-standing disease burden faced by patients with severe eosinophilic asthma in a real-world setting.
Comparison of spinal anesthesia and general anesthesia in inguinal hernia repair in adult: a systematic review and meta-analysis
Authors: Li Lin , Pang Yi , Wang Yongchao , Li Qi , Meng Xiangchao 
Published: March 2020

Abstract
Background
Inguinal hernia repair is one of the most commonly performed surgical procedures. To date, there is no consensus on which anesthesia should be used. The objective of this meta-analysis was to assess the efficacy of spinal anesthesia (SA) vs. general anesthesia (GA) in inguinal hernia repair in adults.

Methods
Eligible studies were identified before January 2020 from PubMed, Embase, ScienceDirect, Cochrane Library, Scopus database as well as reference lists. Outcomes included surgery time, the time in the operation room, the length of hospital stay, pain scores, patient satisfaction, and postoperative complications. Subgroup analysis based on surgical approaches was conducted.

Results
Six randomized controlled trials (RCT) and five cohort studies were included. A total of 2593 patients were analyzed. Compared to GA, SA was associated with a longer surgery time (weighted mean difference [WMD]: − 3.28, 95%confident interval [CI]: − 5.76, − 0.81), particularly in laparoscopic repair. Postoperative pain at 4 h and 12 h were in favor of SA following either open or laparoscopic repairs (standard mean difference [SMD]: 1.58; 95%CI: 0.55, 2.61, SMD: 0.99, 95%CI: 0.37, 1.60, respectively); and considering borderline significance, patients receiving SA might be more satisfied with the anesthesia they used for herniorrhaphy (SMD: -0.32, 95%CI: − 0.70, 0.06). Some major complications of scrotal edema, seroma, wound infection, recurrence, shoulder pain were comparable between the two groups. However, patients receiving SA had an increased risk of postoperative urinary retention and headache when compared with GA (relative ratio [RR]: 0.44, 95% CI: 0.23, 0.86, RR: 0.33, 95% CI: 0.12, 0.92, respectively). There was a tendency that the incidence of postoperative nausea and vomiting was lower in SA than GA (RR: 2.12, 95%CI: 0.95, 4.73), especially in open herniorrhaphy.

Conclusions
SA can be another good choice for pain relief no matter in open or laparoscopic hernia repairs, but it can’t be confirmed that SA is better than GA.