bluuebunny/crossref_metadata_2025_split huggingface dataset:
A review of neurotoxicities associated with immunotherapy and a framework for evaluation
Authors: Burton Leeann B , Eskian Mahsa , Guidon Amanda C , Reynolds Kerry L 
Published: December 2021

AbstractImmuno-oncology agents, including immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T (CAR-T) cell therapies, are increasing in use for a growing list of oncologic indications. While harnessing the immune system against cancer cells has a potent anti-tumor effect, it can also cause widespread autoimmune toxicities that limit therapeutic potential. Neurologic toxicities have unique presentations and can progress rapidly, necessitating prompt recognition. In this article, we review the spectrum of central and peripheral neurologic immune-related adverse events (irAEs) associated with ICI therapies, emphasizing a diagnostic framework that includes consideration of the therapy regimen, timing of symptom onset, presence of non-neurologic irAEs, pre-existing neurologic disease, and syndrome specific features. In addition, we review the immune effector cell-associated neurotoxicity syndrome (ICANS) associated with CAR-T cell therapy and address diagnostic challenges specific to patients with brain metastases. As immunotherapy use grows, so too will the number of patients affected by neurotoxicity. There is an urgent need to understand pathogenic mechanisms, predictors, and optimal treatments of these toxicities, so that we can manage them without sacrificing anti-tumor efficacy.
Preservation of neurocognitive function in the treatment of brain metastases
Authors: Parsons Michael W , Peters Katherine B , Floyd Scott R , Brown Paul , Wefel Jeffrey S 
Published: December 2021

Abstract
Neurocognitive function (NCF) deficits are common in patients with brain metastases, occurring in up to 90% of cases. NCF deficits may be caused by tumor-related factors and/or treatment for the metastasis, including surgery, radiation therapy, chemotherapy, and immunotherapy. In recent years, strategies to prevent negative impact of treatments and ameliorate cognitive deficits for patients with brain tumors have gained momentum. In this review, we report on research that has established the efficacy of preventative and rehabilitative therapies for NCF deficits in patients with brain metastases. Surgical strategies include the use of laser interstitial thermal therapy and intraoperative mapping. Radiotherapy approaches include focal treatments such as stereotactic radiosurgery and tailored approaches such as hippocampal avoidant whole-brain radiotherapy (WBRT). Pharmacologic options include use of the neuroprotectant memantine to reduce cognitive decline induced by WBRT and incorporation of medications traditionally used for attention and memory problems. Integration of neuropsychology into the care of patients with brain metastases helps characterize cognitive patterns, educate patients and families regarding their management, and guide rehabilitative therapies. These and other strategies will become even more important for long-term survivors of brain metastases as treatment options improve.
Advances in radiotherapy for brain metastases
Authors: Gondi Vinai , Meyer Jacquelyn , Shih Helen A 
Published: December 2021

Abstract
As novel systemic therapies yield improved survival in metastatic cancer patients, the frequency of brain metastases continues to increase. Over the years, management strategies have continued to evolve. Historically, stereotactic radiosurgery has been used as a boost to whole-brain radiotherapy (WBRT) but is increasingly being used as a replacement for WBRT. Given its capacity to treat both macro- and micro-metastases in the brain, WBRT has been an important management strategy for years, and recent research has identified technologic and pharmacologic approaches to delivering WBRT more safely. In this review, we outline the current landscape of radiotherapeutic treatment options and discuss approaches to integrating radiotherapy advances in the contemporary management of brain metastases.
Targeted therapy strategies for melanoma brain metastasis
Authors: Saberian Chantal , Sperduto Paul , Davies Michael A 
Published: December 2021

AbstractMelanoma is the most aggressive of the common forms of skin cancer. Metastasis to the central nervous system is one of the most common and deadly complications of this disease. Historically, melanoma patients with brain metastases had a median survival of less than 6 months. However, outcomes of melanoma patients have markedly improved over the last decade due to new therapeutic approaches, including immune and targeted therapies. Targeted therapies leverage the high rate of driver mutations in this disease, which result in the activation of multiple key signaling pathways. The RAS-RAF-MEK-ERK pathway is activated in the majority of cutaneous melanomas, most commonly by point mutations in the Braf serine-threonine kinase. While most early targeted therapy studies excluded melanoma patients with brain metastases, subsequent studies have shown that BRAF inhibitors, now generally given concurrently with MEK inhibitors, achieve high rates of tumor response and disease control in Braf-mutant melanoma brain metastases (MBMs). Unfortunately, the duration of these responses is generally relatively short- and shorter than is observed in extracranial metastases. This review will summarize current data regarding the safety and efficacy of targeted therapies for MBMs and discuss rational combinatorial strategies that may improve outcomes further.
Homotopic functional connectivity disruptions in glioma patients are associated with tumor malignancy and overall survival
Authors: Daniel Andy G S , Hacker Carl D , Lee John J , Dierker Donna , Humphries Joseph B , Shimony Joshua S , Leuthardt Eric C 
Published: December 2021

AbstractBackgroundGliomas exhibit widespread bilateral functional connectivity (FC) alterations that may be associated with tumor grade. Limited studies have examined the connection-level mechanisms responsible for these effects. Given the typically strong FC observed between mirroring/homotopic brain regions in healthy subjects, we hypothesized that homotopic connectivity (HC) is altered in low-grade and high-grade glioma patients and the extent of disruption is associated with tumor grade and predictive of overall survival (OS) in a cohort of de novo high-grade glioma (World Health Organization [WHO] grade 4) patients.MethodsWe used a mirrored FC-derived cortical parcellation to extract blood-oxygen-level-dependent (BOLD) signals and to quantify FC differences between homotopic pairs in normal-appearing brain in a retrospective cohort of glioma patients and healthy controls.ResultsFifty-nine glioma patients (WHO grade 2, n = 9; grade 4 = 50; mean age, 57.5 years) and 30 healthy subjects (mean age, 65.9 years) were analyzed. High-grade glioma patients showed lower HC compared with low-grade glioma patients and healthy controls across several cortical locations and resting-state networks. Connectivity disruptions were also strongly correlated with hemodynamic lags between homotopic regions. Finally, in high-grade glioma patients with known survival times (n = 42), HC in somatomotor and dorsal attention networks were significantly correlated with OS.ConclusionsThese findings demonstrate an association between tumor grade and HC alterations that may underlie global FC changes and provide prognostic information.
Landscape of driver gene events, biomarkers, and druggable targets identified by whole-genome sequencing of glioblastomas
Authors: van de Geer Wesley S , Hoogstrate Youri , Draaisma Kaspar , Robe Pierre A , Bins Sander , Mathijssen Ron H J , French Pim , van de Werken Harmen J G , de Vos Filip Y F 
Published: December 2021

AbstractBackgroundThe survival of glioblastoma patients is poor. Median survival after diagnosis is 15 months, despite treatment involving surgical resection, radiotherapy, and/or temozolomide chemotherapy. Identification of novel targets and stratification strategies of glioblastoma patients to improve patient survival is urgently needed. Whole-genome sequencing (WGS) is the most comprehensive means to identify such DNA-level targets. We report a unique set of WGS samples along with comprehensive analyses of the glioblastoma genome and potential clinical impact of WGS.MethodsOur cohort consisted of 42 glioblastoma tumor tissue and matched whole-blood samples, which were whole-genome sequenced as part of the CPCT-02 study. Somatic single-nucleotide variants, small insertions/deletions, multi-nucleotide variants, copy-number alterations (CNAs), and structural variants were analyzed. These aberrations were harnessed to investigate driver genes, enrichments in CNAs, mutational signatures, fusion genes, and potential targeted therapies.ResultsTumor mutational burden (TMB) was similar to other WGS efforts (1–342 mutations per megabase pair). Mutational analysis in low TMB samples showed that the age-related CpG demethylation signature was dominant, while hyper- and ultramutated tumors had additional defective DNA mismatch repair signatures and showed microsatellite instability in their genomes. We detected chromothripsis in 24% of our cohort, recurrently on chromosomes 1 and 12. Recurrent noncoding regions only resulted in TERT promoter variants. Finally, we found biomarkers and potentially druggable changes in all but one of our tumor samples.ConclusionsWith high-quality WGS data and comprehensive methods, we identified the landscape of driver gene events and druggable targets in glioblastoma patients.
Rollback, scissor-like closure of the Mongol-Okhotsk Ocean and formation of an orocline: magmatic migration based on a large archive of age data
Authors: Wang Tao , Tong Ying , Xiao Wenjiao , Guo Lei , Windley Brian F , Donskaya Tatiana , Li Shan , Tserendash Narantsetseg , Zhang Jianjun 
Published: November 2021

Abstract
Tracing the closure of oceans with irregular margins and the formation of an orocline are crucial for understanding plate reconstruction and continental assembly. The eastern Central Asian Orogenic Belt, where the Mongol-Okhotsk orocline is situated, is one of the world's largest magmatic provinces. Using a large data set of U-Pb zircon ages, we updated the timing of many published igneous rocks, which allowed us to recognize tightly ‘folded’ linear Carboniferous-Jurassic magmatic belts that wrap around the Mongol-Okhotsk suture and their migrations both sutureward and suture-parallel. The new successive magmatic belts reveal a rollback, scissor-like (or zipper-like) closure of the Mongol-Okhotsk Ocean that was fundamentally controlled by coeval subduction rollback and rotation of the Siberian and Mongolian-Erguna blocks. This study also demonstrates the complex mechanisms and processes of the closure of an ocean with irregular margins and the formation of a consequent orocline.
Antibiotic Prophylaxis Prescribing Practice in Head and Neck Tumor Resection and Free Flap Reconstruction
Authors: Daly John Frederick , Gearing Peter Francis , Tang Nicholas Shi Jie , Ramakrishnan Anand , Singh Kasha Priya 
Published: December 2021

Abstract

Background
Adherence to guidelines for antibiotic prophylaxis is often poor and is an important target for antimicrobial stewardship programs. Prescribing audits that suggested poor adherence to guidelines in a plastic surgery department led to a targeted education program to bring antibiotic prescriptions in line with hospital guidelines. We reviewed whether this intervention was associated with changed perioperative prescribing and altered surgical outcomes, including the rate of surgical site infections, specifically looking at clean-contaminated head and neck tumor resections with free flap reconstruction.

Methods
A retrospective cohort study was performed on 325 patients who underwent clean-contaminated head and neck tumor resection and free flap reconstruction from January 1, 2013, to February 19, 2019. Patients were divided into 2 groups, those before (pre-intervention) and after (postintervention) the education campaign. We analyzed patient demographic and disease characteristics, intraoperative and postoperative factors, and surgical outcomes.

Results
Patients pre-intervention were prescribed longer courses of prophylactic antibiotics (median [interquartile range], 9 [8] vs 1 [1]; P &lt; .001), more topical chloramphenicol ointment (21.82% vs 0%; P &lt; .001), and more oral nystatin (36.9% vs 12.2%; P &lt; .001). Patients postintervention had higher rates of recipient infections (36.11% vs 17.06%; P &lt; .001) and donor site infections (6.94% vs 1.19%; P = .006).

Conclusions
Following the education campaign, patients were prescribed shorter courses of prophylactic antibiotics, more of the recommended cefazolin-metronidazole regimen, and fewer topical antibiotics. However, patients also had a higher rate of surgical site infections.
Invasive Mold Infections in Allogeneic Hematopoietic Cell Transplant Recipients in 2020: Have We Made Enough Progress?
Authors: Roth Romain Samuel , Masouridi-Levrat Stavroula , Chalandon Yves , Mamez Anne-Claire , Giannotti Federica , Riat Arnaud , Fischer Adrien , Poncet Antoine , Glampedakis Emmanouil , Van Delden Christian , Kaiser Laurent , Neofytos Dionysios 
Published: December 2021

AbstractBackgroundDespite progress in diagnostic, prevention, and treatment strategies, invasive mold infections (IMIs) remain the leading cause of mortality in allogeneic hematopoietic cell transplant (allo-HCT) recipients.MethodsWe describe the incidence, risk factors, and mortality of allo-HCT recipients with proven/probable IMI in a retrospective single-center 10-year (01/01/2010–01/01/2020) cohort study.ResultsAmong 515 allo-HCT recipients, 48 (9.3%) patients developed 51 proven/probable IMI: invasive aspergillosis (IA; 34/51, 67%), mucormycosis (9/51, 18%), and other molds (8/51, 15%). Overall, 35/51 (68.6%) breakthrough IMIs (bIMIs) were identified: 22/35 (62.8%) IA and 13/35 (37.1%) non-IA IMI. One-year IMI cumulative incidence was 7%: 4.9% and 2.1% for IA and non-IA IMI, respectively. Fourteen (29.2 %), 10 (20.8%), and 24 (50.0%) patients were diagnosed during the first 30, 31–180, and &gt;180 days post-HCT, respectively. Risk factors for IMI included prior allo-HCT (sub hazard ratio [SHR], 4.06; P = .004) and grade ≥2 acute graft-vs-host disease (aGvHD; SHR, 3.52; P &lt; .001). All-cause 1-year mortality was 33% (170/515): 48% (23/48) and 31.5% (147/467) for patients with and without IMI (P = .02). Mortality predictors included disease relapse (hazard ratio [HR], 7.47; P &lt; .001), aGvHD (HR, 1.51; P = .001), CMV serology–positive recipients (HR, 1.47; P = .03), and IMI (HR, 3.94; P &lt; .001). All-cause 12-week mortality for patients with IMI was 35.4% (17/48): 31.3% (10/32) for IA and 43.8% (7/16) for non-IA IMI (log-rank P = .47). At 1 year post–IMI diagnosis, 70.8% (34/48) of the patients were dead.ConclusionsIA mortality has remained relatively unchanged during the last 2 decades. More than two-thirds of allo-HCT recipients with IMI die by 1 year post–IMI diagnosis. Dedicated intensified research efforts are required to further improve clinical outcomes.
Polymyxin B and low-dose hydrocortisone treatment in a patient with uroseptic shock in a rural health unit
Authors: Arai Toshio , Mori Yuichiro , Yoshizaki Saori , Ando Ryo , Natori Shunsuke , Morishita Shun , Otani Miyu , Numata Atsushi , Osanai Hiroaki 
Published: December 2021

ABSTRACT
Sepsis has a high mortality rate; thus, in the intensive care unit, early diagnosis and adjunctive treatments are crucial. However, generally, most patients with sepsis from rural area initially visit the emergency department at a rural hospital and are managed in general medical wards in Japan. Here we report on an 81-year-old Japanese female manifesting septic shock caused by the upper urinary tract infection of extended-spectrum beta-lactamase-producing Escherichia coli secondary to the left ureter obstruction by the urothelial carcinoma. Broad-spectrum antibiotics were administered. Although critical for the source control of infection, drainage of the ureteropelvic junction could not be performed immediately because of catecholamine-resistant hypotension. Hence, we administered polymyxin B-immobilized fiber column direct hemoperfusion, followed by low-dose hydrocortisone administration. After 8 hours of infusion, she recovered from the septic shock and successfully underwent emergency percutaneous nephrostomy. This presented strategy may provide a new resolution of catecholamine-resistant patients in urosepsis.
Case report of primary CD20 negative diffuse large B-cell lymphoma
Authors: Devi Kanti , Ali Natashi , Ahmed Arsalan 
Published: December 2021

ABSTRACT
Few groups of aggressive non-Hodgkin’s lymphomas (NHL) that are refractory to standard chemotherapy are rarely reported. Primary CD20 negative diffuse large B cell lymphoma (DLBCL) without human immunodeficiency virus infection is an uncommon presentation and this case report is challenging in terms of diagnosis and treatment as well.
Indication and outcome of lupus anticoagulant and antiphospholipid antibodies testing in routine clinical practice
Authors: Kempers Eva K , Dalm Virgil A S H , van Rijn Marie Josee E , Mulders Annemarie G M G J , Leebeek Frank W G , de Maat Moniek P M , Jansen A J Gerard 
Published: December 2021

Abstract

Objectives
Lupus anticoagulans (LACs) and aPLs, both further summarized as aPL, are frequently assessed in routine daily clinical practice in diagnostic workups for suspected autoimmune diseases or to test for underlying risk factors in patients with thrombosis or obstetric complications. The aim of this study was to determine the prevalence of aPL positivity in patients with an indication for aPL testing in routine clinical practice.

Methods
In this retrospective single-centre study, indication for aPL testing, aPL test results and clinical data were collected for patients tested between June 2015 and April 2018.

Results
During the study period, 16 847 single aPL tests were performed in 2139 patients. In 212 patients one or more positive aPL test was found, confirmed in 43.9% with a second positive test. Indications for aPL testing were diagnostic workup/follow-up of autoimmune diseases (33.6%), thrombosis (21.4%) and obstetric complications (28%). Seventy-four patients (3.5% of all patients) fulfilled the criteria of APS, of whom 51% were newly diagnosed. Second positive aPL titres and titres of APS patients were significantly higher compared with positive aPL titres at the first measurement (P &lt; 0.05). Patients with indications of arterial thrombosis and diagnostic workup/follow-up of autoimmune diseases had significantly higher levels of aCL IgG and anti-β2 glycoprotein I (β2GPI) IgG compared with patients with other indications.

Conclusion
The prevalence of one or more positive aPL test was 9.9% and APS was diagnosed in 3.5% of the patients. Patients with arterial thrombosis had significantly higher anti-β2GPI IgG and aCL IgG, which should be confirmed in future studies.
Fragility fractures and prescriptions of medications for osteoporosis in patients with polymyalgia rheumatica: results from the PMR Cohort Study
Authors: Sokhal Balamrit Singh , Hider Samantha L , Paskins Zoe , Mallen Christian D , Muller Sara 
Published: December 2021

Abstract

Objectives
PMR is a common indication for long-term glucocorticoid treatment, leading to an increased risk of osteoporosis and fragility fractures. Guidelines recommend calcium and vitamin D for all patients, in addition to anti-resorptive agents for high-risk patients. The aim of this study was to investigate falls and fragility fracture history and the use of medications for osteoporosis in a PMR cohort.

Methods
Six hundred and fifty-two people with incident PMR responded to a postal survey. Self-reported data on falls, fragility fracture history and medication were collected at baseline. Follow-up data on fragility fractures (hip, wrist and spine) and falls were collected at 12 and 24 months. Logistic regression was used to assess the association between baseline characteristics and fractures.

Results
Fewer than 50% of respondents received osteoporosis treatments, including supplements. One hundred and twelve (17.2%) participants reported a fragility fracture at baseline, 72 participants reported a fracture at 12 months, and 62 reported a fracture at 24 months. Baseline history of falls was most strongly associated with fracture at 12 (odds ratio 2.35; 95% CI: 1.35, 4.12) and 24 months (1.91; 1.05, 3.49) when unadjusted for previous fractures.

Conclusion
Fracture reporting is common in people with PMR. To improve fracture prevention, falls assessment and interventions need to be considered. A history of falls could help to inform prescribing decisions around medications for osteoporosis. Future research should consider both pharmacological and non-pharmacological approaches to reducing fracture risk.
The Battisti Case: A Legal-Historical Reconstruction
Authors: Fischel de Andrade José H 
Published: November 2021

Abstract
The Battisti Case constitutes a rare high-profile case of decision-making and judicial ruling on the (hardly ever explored) interpretation and implementation of refugee law by political, technical, and judicial actors in Latin America. It concerns an Italian citizen, Cesare Battisti, sentenced twice to life imprisonment who, after escaping from prison, fled to Mexico, France, Brazil, and Bolivia. Even though Italy had twice attempted to have Mr Battisti extradited from both France (1991 and 2003) and Brazil (2007 and 2017), his extradition has never been materialised. In 2019 he was removed from Bolivia to Italy, where he has been serving his sentences. This study analyses the facts prior to the 2007 Italian extradition request, Mr Battisti’s application for refugee status, the Brazilian Supreme Court’s main extradition ruling, the presidential decision on his non-extradition, Mr Battisti’s last years in Brazil and removal from Bolivia, and his confession and the execution of his prison sentence. This piece analyses a case where several parties seem to be in the wrong: the prosecuted criminal and former protecting States have misused the asylum regime, and the country where the prisoner is serving his sentence is seemingly aggravating his situation as a result of his “personal condition”.