bluuebunny/crossref_metadata_2025_split huggingface dataset:
Updated systematic review and meta-analysis of extended adjuvant temozolomide in patients with newly diagnosed glioblastoma
Authors: Gupta Tejpal , Selvarajan Jeevi Mona Priyadharshni , Kannan Sadhana , Menon Nandini , Dasgupta Archya , Chatterjee Abhishek 
Published: July 2023

Abstract

Background
Contemporary standard-of-care for newly diagnosed glioblastoma (GBM) is maximal safe resection followed by postoperative focal conformal radiotherapy (RT) plus concurrent temozolomide (TMZ) and 6-cycles of adjuvant TMZ (Stupp regimen). However, many patients continue to receive extended adjuvant TMZ (beyond 6-cycles) without solid scientific evidence. This review pools data from nonrandomized studies and randomized controlled trials (RCTs) comparing extended adjuvant TMZ (&gt;6-cycles) to standard adjuvant TMZ (6-cycles) in patients with newly diagnosed GBM for updated evidence-synthesis.

Methods
This systematic review and meta-analysis was carried out in accordance with the Cochrane methodology including quality assessment of primary studies. Primary outcome of interest was comparative efficacy defined as progression-free survival (PFS) and overall survival (OS). Hazard ratios (HRs) for PFS and OS with corresponding 95% confidence interval (CIs) were extracted/computed from individual primary studies and pooled using random-effects model. Any p-value &lt;0.05 was considered statistically significant.

Results
Evidence-synthesis was based on pooling of data from 2578 patients enrolled in 16 nonrandomized comparative studies and 5 RCTs. Overall, extended adjuvant TMZ was associated with statistically significant reduction in the risk of progression (HR = 0.72, 95%CI: 0.60–0.87; p = 0.007) and death (HR = 0.71, 95%CI: 0.57–0.90; p = 0.004) compared to standard adjuvant TMZ. However, on subgroup analysis, survival benefit of extended adjuvant TMZ was limited to data synthesized from retrospective nonrandomized comparative studies with no statistically significant difference in outcomes seen after pooling of data from RCTs only.

Conclusion
Apparent survival benefit of extended adjuvant TMZ in newly diagnosed GBM is largely driven by nonrandomized comparative studies with high inherent potential for multiple biases.
Platelet TLR7 is essential for the formation of platelet–neutrophil complexes and low-density neutrophils in lupus nephritis
Authors: Tay Sen Hee , Zharkova Olga , Lee Hui Yin , Toh Michelle Min Xuan , Libau Eshele Anak , Celhar Teja , Narayanan Sriram , Ahl Patricia Jennifer , Ong Wei Yee , Joseph Craig , Lim Jeffrey Chun Tatt , Wang Lingzhi , Larbi Anis , Liang Shen , Lateef Aisha , Akira Shizuo , Ling Lieng Hsi , Thamboo Thomas Paulraj , Yeong Joe Poh Seng , Lee Bernett Teck Kwong , Edwards Steven W , Wright Helen L , MacAry Paul Anthony , Connolly John E , Fairhurst Anna-Marie 
Published: July 2023

Abstract

Objectives
Platelets and low-density neutrophils (LDNs) are major players in the immunopathogenesis of SLE. Despite evidence showing the importance of platelet–neutrophil complexes (PNCs) in inflammation, little is known about the relationship between LDNs and platelets in SLE. We sought to characterize the role of LDNs and Toll-like receptor 7 (TLR7) in clinical disease.

Methods
Flow cytometry was used to immunophenotype LDNs from SLE patients and controls. The association of LDNs with organ damage was investigated in a cohort of 290 SLE patients. TLR7 mRNA expression was assessed in LDNs and high-density neutrophils (HDNs) using publicly available mRNA sequencing datasets and our own cohort using RT-PCR. The role of TLR7 in platelet binding was evaluated in platelet–HDN mixing studies using TLR7-deficient mice and Klinefelter syndrome patients.

Results
SLE patients with active disease have more LDNs, which are heterogeneous and more immature in patients with evidence of kidney dysfunction. LDNs are platelet bound, in contrast to HDNs. LDNs settle in the peripheral blood mononuclear cell (PBMC) layer due to the increased buoyancy and neutrophil degranulation from platelet binding. Mixing studies demonstrated that this PNC formation was dependent on platelet–TLR7 and that the association results in increased NETosis. The neutrophil:platelet ratio is a useful clinical correlate for LDNs, and a higher NPR is associated with past and current flares of LN.

Conclusions
LDNs sediment in the upper PBMC fraction due to PNC formation, which is dependent on the expression of TLR7 in platelets. Collectively, our results reveal a novel TLR7-dependent crosstalk between platelets and neutrophils that may be an important therapeutic opportunity for LN.
Fulfilling the Promise of RNA Therapies for Cardiac Repair and Regeneration
Authors: Giacca Mauro 
Published: July 2023

Abstract
The progressive appreciation that multiple types of RNAs regulate virtually all aspects of tissue function and the availability of effective tools to deliver RNAs in vivo now offers unprecedented possibilities for obtaining RNA-based therapeutics. For the heart, RNA therapies can be developed that stimulate endogenous repair after cardiac damage. Applications in this area include acute cardioprotection after ischemia or cancer chemotherapy, therapeutic angiogenesis to promote new blood vessel formation, regeneration to form new cardiac mass, and editing of mutations to cure inherited cardiac disease. While the potential of RNA therapeutics for all these conditions is exciting, the field is still in its infancy. A number of roadblocks need to be overcome for RNA therapies to become effective, in particular, related to the problem of delivering RNA medicines into the cells and targeting them specifically to the heart.
Fostering Community-Engaged Research on Criminal Legal Innovations with Logic Models
Authors: Epperson Matthew W , Guz Samantha , Sarantakos Sophia P 
Published: July 2023

Abstract
There is a persistent disconnect between research and practice, both in the social work profession as well as in the criminal legal system. Community-engaged research has been suggested as an approach to bridge this divide, but specific tools are needed to integrate research and practice efforts. This article presents three distinct logic model development processes that occurred in collaborative research and practice efforts in the context of criminal legal programming, including prosecutor-led diversion programs, a high-intensity drug court, and a multiagency justice and mental health collaborative. Logic model development incorporated multiple forms of program information using collaborative reflexivity, an approach focused on understanding the relationship between knowledge and power in the research process. For each program, the authors describe the context and process of logic model development, and how the logic models were used by both practitioners and researchers. The authors discuss how collaborative logic model development can facilitate community-engaged research, strengthen the research–practice connection, and advance applied social work scholarship.
Cardiac RGS7 and RGS11 drive TGFβ1‐dependent liver damage following chemotherapy exposure
Authors: Das Kiran , Basak Madhuri , Mahata Tarun , Biswas Sayan , Mukherjee Sukhes , Kumar Pranesh , Moniruzzaman Mahammed , Stewart Adele , Maity Biswanath 
Published: July 2023

AbstractOff target damage to vital organ systems is an unfortunate side effect of cancer chemotherapy and remains a major limitation to the use of these essential drugs in the clinic. Despite decades of research, the mechanisms conferring susceptibility to chemotherapy driven cardiotoxicity and hepatotoxicity remain unclear. In the livers of patients with a history of chemotherapy, we observed a twofold increase in expression of G protein regulator RGS7 and a corresponding decrease in fellow R7 family member RGS11. Knockdown of RGS7 via introduction of RGS7 shRNA via tail vein injection decreased doxorubicin‐induced hepatic collagen and lipid deposition, glycogen accumulation, and elevations in ALT, AST, and triglycerides by approximately 50%. Surprisingly, a similar result could be achieved via introduction of RGS7 shRNA directly to the myocardium without impacting RGS7 levels in the liver directly. Indeed, doxorubicin‐treated cardiomyocytes secrete the endocrine factors transforming growth factor β1 (TGFβ1) and TGFβ superfamily binding protein follistatin‐related protein 1 (FSTL1). Importantly, RGS7 overexpression in the heart was sufficient to recapitulate the impacts of doxorubicin on the liver and inhibition of TGFβ1 signaling with the receptor blocker GW788388 ameliorated the effect of cardiac RGS7 overexpression on hepatic fibrosis, steatosis, oxidative stress, and cell death as well as the resultant elevation in liver enzymes. Together these data demonstrate that RGS7 controls both the release of TGFβ1 from the heart and the profibrotic and pro‐oxidant actions of TGFβ1 in the liver and emphasize the functional significance of endocrine cardiokine signaling in the pathogenesis of chemotherapy drive multiorgan damage.
Vimentin‐mediated myosin 10 aggregation at tips of cell extensions drives MT1‐MMP‐dependent collagen degradation in colorectal cancer
Authors: Ostrowska‐Podhorodecka Zofia , Ali Aiman , Norouzi Masoud , Ding Isabel , Abbasi Sevil , Arora Pamma D. , Wong Timothy H. F. , Magalhaes Marco , McCulloch Christopher A. 
Published: July 2023

AbstractColorectal cancer (CRC) is a high prevalence adenocarcinoma with progressive increases in metastasis‐related mortality, but the mechanisms governing the extracellular matrix (ECM) degradation important for metastasis in CRC are not well‐defined. We investigated a functional relationship between vimentin (Vim) and myosin 10 (Myo10), and whether this relationship is associated with cancer progression. We tested the hypothesis that Vim regulates the aggregation of Myo10 at the tips of cell extensions, which increases membrane‐type 1 matrix metalloproteinase (MT1‐MMP)‐associated local collagen proteolysis and ECM degradation. Analysis of CRC samples revealed colocalization of Vim with Myo10 and MT1‐MMP in cell extensions adjacent to sites of collagen degradation, suggesting an association with local cell invasion. We analyzed cultured CRC cells and fibroblasts and found that Vim accelerates aggregation of Myo10 at cell tips, which increases the cell extension rate. Vim stabilizes the interaction of Myo10 with MT1‐MMP, which in turn increases collagenolysis. Vim depletion reduced the aggregation of Myo10 at the cell extension tips and MT1‐MMP‐dependent collagenolysis. We propose that Vim interacts with Myo10, which in turn associates with MT1‐MMP to facilitate the transport of these molecules to the termini of cell extensions and there enhance cancer invasion of soft connective tissues.
Psychological Journey and Coping Styles of Parents of Infants With Biliary Atresia
Authors: Zhang Cheng-Lu , Wu Ying , Bao Ying , Jiang Wen-Yi , Hu Xiao-Jing 
Published: July 2023

Background:Biliary atresia is a rare and serious neonatal disease that affects the quality of life of both infants and parents. There is currently limited literature on the experiences of parents with infants diagnosed with biliary atresia.Purpose:To explore the psychological journey and coping styles of parents of infants with biliary atresia in a single center in Shanghai, China.Methods:A qualitative study design was used. Face-to-face and semistructured interviews were conducted with 10 parents of infants with biliary atresia. Colaizzi's method of data analysis was utilized, using NVivo 11.0 software.Results:The psychological journey and coping styles of parents could be divided into 4 stages. Different themes were extracted at different stages: before diagnosis, parents experienced complex emotions and actively sought treatment; at the diagnosis stage, negative emotions dominated and parents convinced themselves to accept reality; in the postoperative stage, positive emotions, accepting reality, active response, and the need to learn to take care of their infant gradually appeared; and at the discharge stage, parents accepted the coexistence of positive and negative emotions and the variety of needs that emerged.Implications for Practice:The findings of the study may help healthcare professionals identify and focus on the psychological needs of parents of infants with biliary atresia, leading them to implement effective coping strategies to increase the caregiving ability of parents.Implications for Research:Future research should explore the effects of supportive interventions for parents of infants with serious chronic illnesses.
Biomarker Signatures of Severe Acute Kidney Injury in a Critically Ill Cohort of COVID-19 and Non-COVID-19 Acute Respiratory Illness
Authors: Sathe Neha A. , Mostaghim Ana , Barnes Elizabeth , O’Connor Nicholas G. , Sahi Sharon K. , Sakr Sana S. , Zahlan Jana M. , Smith Craig H. , Fitzpatrick Michael , Morrell Eric D. , Liles W. Conrad , Bhatraju Pavan K. 
Published: July 2023

IMPORTANCE:
Kidney and lung injury are closely inter-related during acute respiratory illness, but the molecular risk factors that these organ injuries share are not well defined.

OBJECTIVES:
We identified plasma biomarkers associated with severe acute kidney injury (AKI) during acute respiratory illness, and compared them to biomarkers associated with severe acute respiratory failure (ARF).

DESIGN, SETTINGS, AND PARTICIPANTS:
Prospective observational cohort study enrolling March 2020 through May 2021, at three hospitals in a large academic health system. We analyzed 301 patients admitted to an ICU with acute respiratory illness.

MAIN OUTCOMES AND MEASURES:
Outcomes were ascertained between ICU admission and day 14, and included: 1) severe AKI, defined as doubling of serum creatinine or new dialysis and 2) severe ARF, which included new or persistent need for high-flow oxygen or mechanical ventilation. We measured biomarkers of immune response and endothelial function, pathways related to adverse kidney and lung outcomes, in plasma collected within 24 hours of ICU admission. Severe AKI occurred in 48 (16%), severe ARF occurred in 147 (49%), and 40 (13%) patients experienced both. Two-fold higher concentrations of soluble tumor necrosis factor receptor-1 (sTNFR-1) (adjusted relative risk [aRR], 1.56; 95% CI, 1.24–1.96) and soluble triggering receptor on myeloid cells-1 (sTREM-1) (aRR, 1.85; 95% CI, 1.42–2.41), biomarkers of innate immune activation, were associated with higher risk for severe AKI after adjustment for age, sex, COVID-19, and Acute Physiology and Chronic Health Evaluation-III. These biomarkers were not significantly associated with severe ARF. Soluble programmed cell death receptor-1 (sPDL-1), a checkpoint pathway molecule, as well as soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular adhesion molecule-1 (sVCAM-1), molecules involved with endothelial-vascular leukocyte adhesion, were associated with both severe AKI and ARF.

CONCLUSIONS AND RELEVANCE:
sTNFR-1 and sTREM-1 were linked strongly to severe AKI during respiratory illness, while sPDL-1, sICAM-1 and sVCAM-1 were associated with both severe AKI and ARF. These biomarker signatures may shed light on pathophysiology of lung-kidney interactions, and inform precision medicine strategies for identifying patients at high risk for these organ injuries.
Comparison of Tumor Bed Delineation Using a Novel Radiopaque Filament Marker Versus Surgical Clips for Targeting Breast Cancer Radiotherapy
Authors: Shukla Utkarsh , Langner Ulrich W. , Linshaw David , Tan Sydney , Huber Kathryn E. , Miller Chelsea J. , Yu Esther , Leonard Kara L. , Sueyoshi Mark , Diamond Brett , Edmonson David , Wazer David E. , Gass Jennifer , Hepel Jaroslaw T. 
Published: July 2023

Background:
Accuracy of tumor bed (TB) delineation is essential for targeting boost doses or partial breast irradiation. Multiple studies have shown high interobserver variability with standardly used surgical clip markers (CMs). We hypothesize that a radiopaque filament marker (FM) woven along the TB will improve TB delineation consistency.

Methods:
An FDA-approved FM was intraoperatively used to outline the TB of patients undergoing lumpectomy. Between January 2020 and January 2022, consecutive patients with FM placed after either (1) lumpectomy or (2) lumpectomy with oncoplastic reconstruction were identified and compared with those with CM. Six “experts” (radiation oncologists specializing in breast cancer) across 2 institutions independently defined all TBs. Three metrics (volume variance, dice coefficient, and center of mass [COM] deviation). Two-tailed paired samples t tests were performed to compare FM and CM cohorts.

Results:
Twenty-eight total patients were evaluated (14 FM and 14 CM). In aggregate, differences in volume between expert contours were 29.7% (SD ± 58.8%) with FM and 55.4% (SD ± 105.9%) with CM (P < 0.001). The average dice coefficient in patients with FM was 0.54 (SD ± 0.15), and with CM was 0.44 (SD ± 0.22) (P < 0.001). The average COM deviation was 0.63 cm (SD ± 0.53 cm) for FM and 1.05 cm (SD ± 0.93 cm) for CM; (P < 0.001). In the subset of patients who underwent lumpectomy with oncoplastic reconstruction, the difference in average volume was 21.8% (SD ± 20.4%) with FM and 52.2% (SD ± 64.5%) with CM (P<0.001). The average dice coefficient was 0.53 (SD ± 0.12) for FM versus 0.39 (SD ± 0.24) for CM (P < 0.001). The average COM difference was 0.53 cm (SD ± 0.29 cm) with FM versus 1.25 cm (SD ± 1.08 cm) with CM (P < 0.001).

Conclusion:
FM consistently outperformed CM in the setting of both standard lumpectomy and complex oncoplastic reconstruction. These data suggest the superiority of FM in TB delineation.
Similar Growth Outcomes in Children with Inflammatory Bowel Disease Initiated on Infliximab Originator or Biosimilar
Authors: McClinchie Madeline G. , Lakhani Alyshah , Abdel-Rasoul Mahmoud , McNicol Megan , Shkhkhalil Ala K. , Boyle Brendan B. , Maltz Ross M. 
Published: July 2023

Background:
Growth is an important clinical outcome, especially in childhood-onset inflammatory bowel disease (IBD). Prior research has demonstrated growth improvements with infliximab therapy. There are limited studies evaluating whether clinical and growth outcomes in children initiated on the infliximab originator and infliximab biosimilar are similar.

Methods:
This was a single-center retrospective review of patients with IBD, younger than 17 years old, and initiated on the infliximab originator or biosimilar for at least 12 months between April 2016 and February 2021. Propensity score matching was utilized. Laboratory values, disease activity scores, and growth values were collected at baseline (prior to infliximab initiation), 6 months, and 12 months post initiation. Linear mixed models with random intercepts were used to test differences in measures over time and between study groups.

Results:
There were 113 patients on the originator and 39 patients on a biosimilar who met eligibility criteria. Propensity score methodology identified 37 dyads (1:1 match). Weight, height, and body mass index z scores increased over time (from baseline to 12 months) for both groups (P < 0.05) and there was a similar rate of change between study groups. Clinical outcomes of lab values (albumin, C-reactive protein, and hemoglobin) and disease activity scoring were similar from baseline to 12 months between study groups.

Conclusions:
There were similar improvements in growth and clinical outcomes in patients initiated on the infliximab originator compared to an infliximab biosimilar agent. This study adds to the limited research evaluating whether infliximab biosimilars have similar growth outcomes in children with IBD.
Operationalization of Clinical Placements in Graduate Nursing
Authors: Gonzalez John D. , Eckhardt Ann L. 
Published: July 2023

Background:
Nurse practitioner (NP) program accreditation standards require that programs secure clinical placements for all students. As NP programs increase enrollment to meet the demand for primary care providers, it is vital that they deploy a formalized clinical placement process that ensures all students have a clinical placement.

Problem:
Although NP programs have consistently increased enrollment, the shortage of clinical sites and preceptors continues to be a barrier to admission.

Approach:
Described in this article is the operationalization of graduate nursing clinical placement at one large university with 7 NP tracks.

Outcomes:
A formalized clinical placement process ensures that all students receive an appropriate placement and graduate on time. Having a dedicated team of NP faculty members to provide clinical placements services for NP students is highly effective.
Engagement Across Professions
Authors: Chipman Micheline L. , Schreiber Christine M. , Fey Jamie M. , Lane Susan J. , DiLisio Chris , Mallory Leah A. 
Published: July 2023

Introduction
Simulation is an ideal tool for interprofessional (IP) team training. Debriefing after simulation is key to IP learning, although engagement and participation may be adversely influenced by cultural and hierarchical barriers. This mixed-methods study explored factors influencing learner engagement and participation in IP debriefing and the experience of “silent but apparently engaged” participants.

Methods
Semistructured profession-specific focus groups were conducted with participants from a weekly IP pediatric simulation program. Focus groups were recorded, transcribed, and thematically analyzed. Eligible participants were assigned to “silent” or “verbal” groups according to observed behavior and received a questionnaire. Participants' self-rated engagement scores were compared using a t test.

Results
Thirty-six of 81 eligible participants were included, 13 completed a questionnaire, and 23 (8 physicians, 10 nursing staff, 4 pharmacists, 1 respiratory therapist) participated in 13 focus groups. Twenty-two subthemes were grouped into 6 themes: psychological safety, realism, distractors, stress, group characteristics, and facilitator behavior, with differences in perspective according to profession. Of the 36 respondents, 18 were “silent” and 18 “verbal.” Self-rated engagement scores differed between groups (3.65 vs. 4.17, P = 0.06); however, “silent” participants described themselves as engaged.

Conclusions
Themes identified that influenced learner engagement in debriefing included aspects of prebriefing and the simulation. Some aligned with general simulation best practices, such as psychological safety, prebriefing, and facilitator behavior. Findings unique to IP simulation included importance of realism to nonphysician professions, protecting time for training, group composition, and direct probing by cofacilitators to decrease physician bias and emphasize IP contributions. Silent participants reported engagement.
Damage control surgery in emergency general surgery: What you need to know
Authors: Risinger William B. , Smith Jason W. 
Published: July 2023

ABSTRACT
Damage-control surgery (DCS) is a strategy adopted to limit initial operative interventions in the unstable surgical patient, delaying definitive repairs and abdominal wall closure until physiologic parameters have improved. Although this concept of “physiology over anatomy” was initially described in the management of severely injured trauma patients, the approaches of DCS have become common in the management of nontraumatic intra-abdominal emergencies.
While the utilization of damage-control methods in emergency general surgery (EGS) is controversial, numerous studies have demonstrated improved outcomes, making DCS an essential technique for all acute care surgeons. Following a brief history of DCS and its indications in the EGS patient, the phases of DCS will be discussed including an in-depth review of preoperative resuscitation, techniques for intra-abdominal source control, temporary abdominal closure, intensive care unit (ICU) management of the open abdomen, and strategies to improve abdominal wall closure.