bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Capacity of the Ovarian Cancer Tumor Microenvironment to Integrate Inflammation Signaling Conveys a Shorter Disease-free Interval
Authors: Jordan Kimberly R. , Sikora Matthew J. , Slansky Jill E. , Minic Angela , Richer Jennifer K. , Moroney Marisa R. , Hu Junxiao , Wolsky Rebecca J. , Watson Zachary L. , Yamamoto Tomomi M. , Costello James C. , Clauset Aaron , Behbakht Kian , Kumar T. Rajendra , Bitler Benjamin G. 
Published: September 2020

Abstract

Purpose:
Ovarian cancer has one of the highest deaths to incidence ratios across all cancers. Initial chemotherapy is effective, but most patients develop chemoresistant disease. Mechanisms driving clinical chemo-response or -resistance are not well-understood. However, achieving optimal surgical cytoreduction improves survival, and cytoreduction is improved by neoadjuvant chemotherapy (NACT). NACT offers a window to profile pre- versus post-NACT tumors, which we used to identify chemotherapy-induced changes to the tumor microenvironment.

Experimental Design:
We obtained matched pre- and post-NACT archival tumor tissues from patients with high-grade serous ovarian cancer (patient, n = 6). We measured mRNA levels of 770 genes (756 genes/14 housekeeping genes, NanoString Technologies), and performed reverse phase protein array (RPPA) on a subset of matched tumors. We examined cytokine levels in pre-NACT ascites samples (n = 39) by ELISAs. A tissue microarray with 128 annotated ovarian tumors expanded the transcriptional, RPPA, and cytokine data by multispectral IHC.

Results:
The most upregulated gene post-NACT was IL6 (16.79-fold). RPPA data were concordant with mRNA, consistent with elevated immune infiltration. Elevated IL6 in pre-NACT ascites specimens correlated with a shorter time to recurrence. Integrating NanoString (n = 12), RPPA (n = 4), and cytokine (n = 39) studies identified an activated inflammatory signaling network and induced IL6 and IER3 (immediate early response 3) post-NACT, associated with poor chemo-response and time to recurrence.

Conclusions:
Multiomics profiling of ovarian tumor samples pre- and post-NACT provides unique insight into chemo-induced changes to the tumor microenvironment. We identified a novel IL6/IER3 signaling axis that may drive chemoresistance and disease recurrence.
Immunomodulation in Pomalidomide, Dexamethasone, and Daratumumab-Treated Patients with Relapsed/Refractory Multiple Myeloma
Authors: Pierceall William E. , Amatangelo Michael D. , Bahlis Nizar J. , Siegel David S. , Rahman Adeeb , Van Oekelen Oliver , Neri Paola , Young Mary , Chung Weiyuan , Serbina Natalya , Parekh Samir , Agarwal Amit , Thakurta Anjan 
Published: September 2020

Abstract

Purpose:
Addition of daratumumab to pomalidomide and low-dose dexamethasone (LoDEX) is a safe and effective combination for relapsed/refractory multiple myeloma treatment. We sought to better understand immune combinational benefit of pomalidomide and daratumumab with LoDEX.

Patients and Methods:
Immunophenotypic changes were analyzed in peripheral blood from longitudinal sampling of patients treated with this triplet regimen from cohort B of the CC4047-MM-014 phase II trial (NCT01946477).

Results:
Consistent with the daratumumab mechanism, treatment led to decreased natural killer (NK) and B cells. In contrast, pronounced increases occurred in activated and proliferating NK and T cells, appreciably in CD8+ T cells, along with reduction in naïve and expansion of effector memory compartments. Timing of T-cell changes correlated with pomalidomide dosing schedule. Enhanced activation/differentiation did not result in increased exhausted T-cell phenotypes or increases in regulatory T cells. Similar immune enhancements were also observed in patients previously refractory to lenalidomide.

Conclusions:
These data support a potential mechanism for enhanced immune-mediated cytotoxicity in which daratumumab-mediated NK-cell diminution is partially offset by pomalidomide effects on the remaining NK-cell pool. Furthermore, daratumumab antimyeloma activity and elimination of CD38+ T cells (regulatory/activated) provide a rationale for therapeutic combination with direct tumoricidal activity and immunomodulation of pomalidomide-directed T-cell enhancements. These data highlight enhancements in immune subpopulations for the combination of daratumumab with pomalidomide and potentially with next-generation cereblon-targeting agents.
β2-adrenoreceptor Signaling Increases Therapy Resistance in Prostate Cancer by Upregulating MCL1
Authors: Hassan Sazzad , Pullikuth Ashok , Nelson Kyle C. , Flores Anabel , Karpova Yelena , Baiz Daniele , Zhu Sinan , Sui Guangchao , Huang Yue , Choi Young A. , D'Agostino Ralph , Hemal Ashok , von Holzen Urs , Debinski Waldemar , Kulik George 
Published: September 2020

Abstract

There is accumulating evidence that continuous activation of the sympathetic nervous system due to psychosocial stress increases resistance to therapy and accelerates tumor growth via β2-adrenoreceptor signaling (ADRB2). However, the effector mechanisms appear to be specific to tumor type. Here we show that activation of ADRB2 by epinephrine, increased in response to immobilization stress, delays the loss of MCL1 apoptosis regulator (MCL1) protein expression induced by cytotoxic drugs in prostate cancer cells; and thus, increases resistance of prostate cancer xenografts to cytotoxic therapies. The effect of epinephrine on MCL1 protein depended on protein kinase A (PKA) activity, but was independent from androgen receptor expression. Furthermore, elevated blood epinephrine levels correlated positively with an increased MCL1 protein expression in human prostate biopsies. In summary, we demonstrate that stress triggers an androgen-independent antiapoptotic signaling via the ADRB2/PKA/MCL1 pathway in prostate cancer cells.

Implications:
Presented results justify clinical studies of ADRB2 blockers as therapeutics and of MCL1 protein expression as potential biomarker predicting efficacy of apoptosis-targeting drugs in prostate cancer.
Risk of Paradoxical Embolism (RoPE)–Estimated Attributable Fraction Correlates With the Benefit of Patent Foramen Ovale Closure
Authors: Kent David M. , Saver Jeffrey L. , Ruthazer Robin , Furlan Anthony J. , Reisman Mark , Carroll John D. , Smalling Richard W. , Jüni Peter , Mattle Heinrich P. , Meier Bernhard , Thaler David E. 
Published: September 2020

Background and Purpose:
In patients with cryptogenic stroke and patent foramen ovale (PFO), the Risk of Paradoxical Embolism (RoPE) Score has been proposed as a method to estimate a patient-specific “PFO-attributable fraction”—the probability that a documented PFO is causally-related to the stroke, rather than an incidental finding. The objective of this research is to examine the relationship between this RoPE-estimated PFO-attributable fraction and the effect of closure in 3 randomized trials.

Methods:
We pooled data from the CLOSURE-I (Evaluation of the STARFlex Septal Closure System in Patients With a Stroke and/or Transient Ischemic Attack due to Presumed Paradoxical Embolism through a Patent Foramen Ovale), RESPECT (Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment), and PC (Clinical Trial Comparing Percutaneous Closure of Patent Foramen Ovale [PFO] Using the Amplatzer PFO Occluder With Medical Treatment in Patients With Cryptogenic Embolism) trials. We examine the treatment effect of closure in high RoPE score (≥7) versus low RoPE score (<7) patients. We also estimated the relative risk reduction associated with PFO closure across each level of the RoPE score using Cox proportional hazard analysis. We estimated a patient-specific attributable fraction using a PC trial–compatible (9-point) RoPE equation (omitting the neuroradiology variable), as well as a 2-trial analysis using the original (10-point) RoPE equation. We examined the Pearson correlation between the estimated attributable fraction and the relative risk reduction across RoPE strata.

Results:

In the low RoPE score group (<7, n=912), the rate of recurrent strokes per 100 person-years was 1.37 in the device arm versus 1.68 in the medical arm (hazard ratio, 0.82 [0.42–1.59]
P
=0.56) compared with 0.30 versus 1.03 (hazard ratio, 0.31 [0.11–0.85]
P
=0.02) in the high RoPE score group (≥7, n=1221); treatment-by-RoPE score group interaction,
P
=0.12. The RoPE score estimated attributable fraction anticipated the relative risk reduction across all levels of the RoPE score, in both the 3-trial (
r
=0.95,
P
<0.001) and 2-trial (
r
=0.92,
P
<0.001) analyses.

Conclusions:
The RoPE score estimated attributable fraction is highly correlated to the relative risk reduction of device versus medical therapy. This observation suggests the RoPE score identifies patients with cryptogenic stroke who are likely to have a PFO that is pathogenic rather than incidental.
Study in three phases: An Adaptive Sound Installation
Authors: Panariello Claudio 
Published: September 2020

Abstract
Study in three phases is an adaptive site-specific sound installation that includes 22 solenoids placed on metallic arches that surround visitors and react to environmental perturbations, creating a self-regulating soundscape of metallic hits that serves to renew the visitors’ acoustic perspective. Adaptivity is a crucial aspect of the work: Similar perturbations will not generally cause similar reactions from the installation based on past interactions, thus allowing evolution over time to play a key role artistically and technically. This article discusses the author's position on adaptivity in music interaction and composition and reports on the technical and artistic aspects of the installation.
The Role of Upper-Level Coupling on Great Plains Low-Level Jet Structure and Variability
Authors: Burrows D. Alex , Ferguson Craig R. , Bosart Lance F. 
Published: September 2020

AbstractThe Great Plains (GP) southerly nocturnal low-level jet (GPLLJ) is a dominant contributor to the region’s warm-season (May–September) mean and extreme precipitation, wind energy generation, and severe weather outbreaks—including mesoscale convective systems. The spatiotemporal structure, variability, and impact of individual GPLLJ events are closely related to their degree of upper-level synoptic coupling, which varies from strong coupling in synoptic trough–ridge environments to weak coupling in quiescent, synoptic ridge environments. Here, we apply an objective dynamic classification of GPLLJ upper-level coupling and fully characterize strongly coupled (C) and relatively uncoupled (UC) GPLLJs from the perspective of the ground-based observer. Through composite analyses of C and UC GPLLJ event samples taken from the European Centre for Medium-Range Weather Forecasts’ Coupled Earth Reanalysis of the twentieth century (CERA-20C), we address how the frequency of these jet types, as well as their inherent weather- and climate-relevant characteristics—including wind speed, direction, and shear; atmospheric stability; and precipitation—vary on diurnal and monthly time scales across the southern, central, and northern subregions of the GP. It is shown that C and UC GPLLJ events have similar diurnal phasing, but the diurnal amplitude is much greater for UC GPLLJs. C GPLLJs tend to have a faster and more elevated jet nose, less low-level wind shear, and enhanced CAPE and precipitation. UC GPLLJs undergo a larger inertial oscillation (Blackadar mechanism) for all subregions, and C GPLLJs have greater geostrophic forcing (Holton mechanism) in the southern and northern GP. The results underscore the need to differentiate between C and UC GPLLJs in future seasonal forecast and climate prediction activities.
The Impact of the COVID-19 Pandemic on Surgical Practice in the Southeastern United States: Results of a Survey of the Membership of the Southeastern Surgical Congress
Authors: Richmond Bryan K. , Dean L. Scott , Farrell Timothy M. 
Published: September 2020

Background The coronavirus disease 2019 (COVID-19) pandemic dramatically altered the delivery of surgical care. Methods Members of the Southeastern Surgical Congress were surveyed regarding system adjustments, personal impact, and productivity losses. Subgroups were analyzed for disproportionate impact across practice models (academic/employed/private), practice communities (urban, suburban, rural), and practice case-mix categories (broad general surgery, narrow general surgery, specialty practice, hospital-based practice). Results 135 respondents reported that 98.5% of surgeons and 97% of hospitals canceled elective cases. Practices and hospitals reduced staffing dramatically. Telemedicine was utilized by most respondents. Hospitals variably implemented system changes, developed tests, and set up diagnostic centers. Most surgeons anticipated resumption of practice and hospital activity by July 1, 2020. More than one-quarter reported worsened financial status and personal well-being. Interestingly, family/personal relationships were improved in more than one-third. Most surgeons anticipate reduced year-end case volumes, clinical productivity, and salary. In subgroup analyses, academic surgeons were more likely than employed and private-practice surgeons to use telemedicine and to work in hospitals with in-house COVID-19 testing. Private-practice surgeons expected decreased financial status, case volumes, relative value units (RVUs), and salary. More rural surgeons anticipate reduced salary than urban and suburban surgeons. Surgeons in narrow general surgery practice reported more furlough of employees than specialty surgeons, hospital-based surgeons, and broad-based general surgeons. Narrow-practice surgeons and specialists were more likely to report RVU reductions and improved family/personal relationships. Discussion The COVID-19 slowdown affected surgeons throughout the southeastern United States. Variations between different practice models, communities, and case-mix categories may help inform surgeons in the future.
Evaluation of Surgical Learning Curve Effect on Obstructive Sleep Apnea Outcomes in Upper Airway Stimulation
Authors: Larsen Christopher , Boyd Christopher , Villwock Mark , Steffen Armin , Heiser Clemens , Boon Maurits , Huntley Colin , Doghramji Karl , Soose Ryan J. , Kominsky Alan , Waters Tina , Withrow Kirk , Parker Noah , Thaler Erica , Dhanda Patil Reena , Green Katherine K. , Chio Eugene , Suurna Maria , Schell Amy , Strohl Kingman 
Published: September 2020

Objective: An increasing number of facilities offer Upper Airway Stimulation (UAS) with varying levels of experience. The goal was to quantify whether a surgical learning curve exists in operative or sleep outcomes in UAS. Methods: International multi-center retrospective review of the ADHERE registry, a prospective international multi-center study collecting UAS outcomes. ADHERE registry centers with at least 20 implants and outcomes data through at least 6-month follow-up were reviewed. Cases were divided into two groups based on implant order (the first 10 or second 10 consecutive implants at a given site). Group differences were assessed using Mann-Whitney U-tests, Chi-squared tests, or Fisher’s Exact tests, as appropriate. A Mann-Kendall trend test was used to detect if there was a monotonic trend in operative time. Sleep outcome equivalence between experience groups was assessed using the two one-sided tests approach. Results: Thirteen facilities met inclusion criteria, contributing 260 patients. Complication rates did not significantly differ between groups ( P = .808). Operative time exhibited a significant downward trend ( P < .001), with the median operative time dropping from 150 minutes for the first 10 implants to 134 minutes for the subsequent 10 implants. The decrease in AHI from baseline to 12-month follow-up was equivalent between the first and second ten (22.8 vs 21.2 events/hour, respectively, P < .001). Similarly, the first and second ten groups had equivalent ESS decreases at 6 months (2.0 vs 2.0, respectively, P < .001). ESS outcomes remained equivalent for those with data through 12-months. Conclusions: Across the centers’ first 20 implants, an approximately 11% reduction operative time was identified, however, no learning curve effect was seen for 6-month or 12-month AHI or ESS over the first twenty implants. Ongoing monitoring through the ADHERE registry will help measure the impact of evolving provider and patient specific characteristics as the number of implant centers increases.
Management of Cerebrospinal Fluid Rhinorrhea in the Sphenoid Sinus Lateral Recess Through an Endoscopic Endonasal Transpterygoid Approach With Obliteration of the Lateral Recess
Authors: He Chao , Zhen Hong-Tao 
Published: September 2020

Background: Cerebrospinal fluid rhinorrhea in the sphenoid sinus lateral recess is a rare occurrence and poses unique challenges due to limited surgical access for surgical repair. Objective: To report our experience of surgical repair of cerebrospinal fluid rhinorrhea in the sphenoid sinus lateral recess through an endoscopic endonasal transpterygoid approach with obliteration of the lateral recess. To evaluate the efficiency of this surgical procedure. Methods: A retrospective study. Twelve cases with cerebrospinal fluid rhinorrhea in the sphenoid sinus lateral recess were reviewed. Assisted by image-guided navigation, cerebrospinal fluid rhinorrhea was repaired through an endoscopic endonasal transpterygoid approach, with obliteration of the lateral recess. Complications and recurrence were recorded. Medical photographs were used. Results: This surgical approach provided a relatively spacious corridor to dissect the sphenoid sinus lateral recess and do postoperative surveillance. The repair area completely healed in 3 months after surgery. Cerebrospinal fluid rhinorrhea in the sphenoid sinus lateral recess was successfully repaired on the first attempt in all cases (100%). No main complications or recurrence was observed during a mean follow-up time of 40.3 months. Conclusion: The endoscopic endonasal transpterygoid approach gives appropriate access for the treatment of spontaneous cerebrospinal fluid rhinorrhea in the sphenoid sinus lateral recess. Multilayer reconstruction of a skull base defect with obliteration of the lateral recess is a reliable and simple method.
Is Preoperative Embolization Necessary for Carotid Paraganglioma Resection: Experience of a Tertiary Center
Authors: Gözen Emine Deniz , Tevetoğlu Fırat , Kara Sinem , Kızılkılıç Osman , Yener Haydar Murat 
Published: September 2020

Purpose: This study was designed to investigate whether preoperative embolization is a useful procedure to decrease blood loss and neurovascular complications for carotid body tumor (CBT) surgery or not. Methods: Medical records of our tertiary care center from 2012 to 2019 were scanned for patients who underwent surgery for CBT, retrospectively. Age, gender, complaint and head and neck examination findings at the time of presentation, preoperative complete blood count parameters, imaging records (cervical magnetic resonance imaging and carotid artery angiography), Shamblin classification, tumor size, intraoperative findings, and postoperative complications were noted. Results: A total of 26 patients were operated due to CBT between 2012 and 2019 in our clinic; preoperative arterial embolization was performed to 15 (57.7%) patients, and 11 (42.3%) patients were operated without embolization. Youngest patient was 24 years old, while oldest was 69 years and mean age was 44.35 ± 12.73. (embolization group: ages ranging between 24 and 64 with a mean of 41.5 ± 11.02 years; in nonembolization group: ages ranging between 26 and 69 with a mean of 48.1 ± 14.3). Embolization status was not significantly related to cranial nerve injury, vascular injury, overall complications, and hematocrit decrease. Arterial injury is more likely to occur with increasing Shamblin class ( r = .39; P = .04). Tumor size is not found to be significantly related to cranial nerve injury, vascular injury, overall complications, and hematocrit decrease, but cranial nerve injury and vascular injury were more likely to occur in large tumors ( r = .34; P = .089 and r = .34; P = .087, respectively). Age was significantly and negatively correlated to vascular injury ( r = −.51; P = .05). Vascular injury was significantly correlated with gender (male predominance: r = −.64; P = .000). Conclusion: Although preoperative arterial embolization is considered to attenuate the complication risk, we found that there was no significant difference among the patients with or without embolization.
Does central sensitization affect hyperalgesia after staged bilateral total knee arthroplasty? A randomized controlled trial
Authors: Koh Hyun Jung , In Yong , Kim Eun Sung , Hwang Jae Woong , Kim Ji Yeong , Lim Soo Jin , Park Hue Jung 
Published: September 2020

Objective Osteoarthritis (OA) patients who undergo staged bilateral total knee arthroplasty (TKA) feel postoperative hyperalgesia in the second operated knee compared with the first knee. Ketamine is an important drug for central temporal summation and inhibition of secondary mechanical hyperalgesia. This study investigated whether central sensitization has a significant effect on hyperalgesia after consecutive operations. Methods Seventy-one of 80 OA patients were randomly allocated to the ketamine or saline group. A bolus of ketamine (group K) or saline (group C) (0.5 mg/kg) was injected before induction and at an infusion rate of 3 µg/kg/minute during surgery. A visual analog scale (VAS) was used to assess resting and moving pain and opioid consumption on postoperative days 1, 2, and 3. Results The difference in the VAS score between stages 1 and 2 (DV2-V1) was higher in the ketamine compared with the saline group. DV2-V1 for movement between the two groups was not inferior for all periods. Ketamine did not show a large analgesic effect on second-operated knee hyperalgesia in staged bilateral TKAs. Conclusions We could not confirm that hyperalgesia was only related to central sensitization with low-dose ketamine. Other factors might be also associated with the hyperexcitability of nociceptive stimuli. Clinical Research Information Service (CRIS) trial registry no: KCT0001481
Arthroscopic Biceps Tenodesis Outcomes: A Comparison of Inlay and Onlay Techniques
Authors: Haidamous Georges , Noyes Matthew P. , Denard Patrick J. 
Published: September 2020

Background: Arthroscopic biceps tenodesis (ABT) high in the groove can be achieved using an inlay or an onlay technique. However, there is little information comparing outcomes between the 2. Purpose: To compare postoperative healing and functional outcomes of ABT high in the groove performed using either an onlay or an inlay technique. Study Design: Cohort study; Level of evidence, 3. Methods: A retrospective study was performed on patients undergoing ABT at the articular margin (high in the groove) at a single center over a 2-year period. An inlay technique using an interference screw was performed during the first year, followed by an onlay technique using a knotless suture anchor during the second. Tendon healing, elbow flexion strength, functional outcome, and complications were evaluated at a postoperative minimum of 1 year. Results: A total of 37 patients with inlay and 53 with onlay ABTs were available for follow-up. There was no difference in range of motion, functional outcome scores, or elbow flexion strength between the groups. A postoperative popeye deformity was noted in 27% of patients in the inlay group as compared with 9.4% of the onlay group ( P = .028). Four patients (10.8%) in the inlay group required revision surgery (2 of which were biceps tenodesis related) as compared with 0% in the onlay group ( P = .015). Conclusion: An onlay technique using a knotless suture anchor for ABT at the top of the articular margin is an acceptable alternative to an inlay technique using an interference screw. The onlay technique was associated with lower rates of postoperative popeye deformity and revision surgery as compared with the inlay technique.