bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bromazolam Blood Concentrations in Postmortem Cases—A British Columbia Perspective
Authors: Mérette Sandrine A M , Thériault Sébastien , Piramide Lei E C , Davis Michael D , Shapiro Aaron M 
Published: January 2023

AbstractBromazolam is a designer benzodiazepine that was first detected in British Columbia in January 2021. Postmortem cases were analyzed using a comprehensive blood drug screening procedure by liquid chromatography–high-resolution mass spectrometry before being retrospectively analyzed using an in-house novel psychoactive substances data processing method. Bromazolam was detected in 41 postmortem cases in 2021 and quantitatively confirmed by standard addition, using liquid chromatography–tandem mass spectrometry. The mean bromazolam concentration observed was 11.4 ± 53.7 ng/mL (median concentration: 1.6 ng/mL), with a range from 0.5 to 319.3 ng/mL and the majority of cases co-occurring with fentanyl. These low concentrations may be indicative of a presumed enhancement of opioid effects, rather than being used as a stand-alone drug. Bromazolam was always detected with opioids (fentanyl and carfentanil), stimulants (methamphetamine) and/or other benzodiazepines (etizolam and flualprazolam). To our knowledge, this is the first report to provide concentrations of bromazolam in postmortem blood samples in Canada.
China National Intellectual Property Administration clarifies administrative adjudication measures for significant patent infringement disputes in pharmaceutical cases
Authors: Yu Qiang 
Published: January 2023

Abstract
The China National Intellectual Property Administration decided that the plaintiff’s administrative adjudication request met the conditions for acceptance according to the Measures for Administrative Adjudication of Significant Patent Infringement Disputes (2021), even if there was an ongoing judicial suit in the People’s Court concerning related patents. Although the defendant had filed an application for invalidation of the plaintiff’s patent, the defendants’ plea to suspend the ongoing patent infringement adjudication was dismissed based on considerations related to fairness and efficiency.
A specific technique of immunolabelling of urinary small extracellular vesicle biomarkers for the diagnostic of renal cancer
Authors: Mallouk Nora , Tan Sisareuth , Scepaniack Claire , Garcin Arnauld , Pradat Camille , Lambert Claude , Li Guorong 
Published: January 2023

Abstract
Small extracellular vesicles (EVs) are characterized by the membrane expression of CD63, CD81 and CD9 tetraspanins. Their size is inferior to 200 nm. They share the same characteristics as the native cells and are found in human fluids. Specific membrane protein biomarkers expressed on small EV are useful for the diagnosis of tumoural pathologies. Clear cell renal cell carcinoma (CCRCC) is diagnosed by imaging examinations and/or tissue biopsy. Carbonic anhydrase IX (CAIX) is a powerful biomarker of CCRCC. The detection of CAIX on small EV from the urine of patients could constitute a liquid biopsy for CCRCC. We have set up a specific protocol for the preparation, the immunostaining characterization and the transmission electron microscopy observation of small EVs isolated from the urine of CCRCC patients. The background labelling was significantly reduced. We successfully detected biomarkers on urinary small EVs from CCRCC patients. This technique could be extended with antibodies directed against other EV biomarkers for the detection and the monitoring of cancer diseases.
Anti-TIF1γ antibody-positive dermatomyositis associated with nivolumab administration in a patient with advanced oesophageal squamous cell carcinoma: A case report and literature review
Authors: Sakurai Takuya , Takahashi Junichiro , Komatsu Teppei , Mitsumura Hidetaka , Iguchi Yasuyuki 
Published: January 2023

ABSTRACT
We report a case of anti-transcriptional intermediary factor 1γ antibody-positive dermatomyositis following nivolumab treatment. The patient was successfully treated with pulse steroid therapy and high-dose intravenous immunoglobulin, followed by oral glucocorticoid treatment. Immune checkpoint inhibitors, such as nivolumab, may induce not only myositis as an immune-related adverse event but also dermatomyositides as a paraneoplastic syndrome by distracting immune tolerance. Differentiating between pathologies is warranted if patients develop myositis after immune checkpoint inhibitor administration.
Automatic detection and segmentation of postoperative cerebellar damage based on normalization
Authors: Zhang Silu , McAfee Samuel S , Patay Zoltan , Pinto Soniya , Scoggins Matthew A 
Published: January 2023

AbstractBackgroundSurgical resection is the gold standard in the treatment of pediatric posterior fossa tumors. However, surgical damage is often unavoidable and its association with postoperative complications is not well understood. A reliable localization and measure of cerebellar damage is fundamental to study the relationship between the damaged cerebellar regions and postoperative neurological outcomes. Existing cerebellum normalization methods are likely to fail on postoperative scans, therefore current approaches to measure postoperative damage rely on manual labelling. In this work, we develop a robust algorithm to automatically detect and measure cerebellum damage in postoperative 3D T1 magnetic resonance imaging (MRI).MethodsIn our approach, normal brain tissues are first segmented using a Bayesian algorithm customized for postoperative scans. Next, the cerebellum is isolated by nonlinear registration of a whole-brain template to the native space. The isolated cerebellum is then normalized into the spatially unbiased atlas (SUIT) space using anatomical information derived from the previous step. Finally, the damage is detected in the atlas space by comparing the normalized cerebellum and the SUIT template.ResultsWe evaluated our damage detection tool on postoperative scans of 153 patients with medulloblastoma based on inspection by human experts. We also designed a simulation to evaluate performance without human intervention and with an explicitly controlled and defined ground truth. Our results show that the approach performs adequately under various realistic conditions.ConclusionsWe develop an accurate, robust, and fully automatic localization and measurement of cerebellar damage in the atlas space using postoperative MRI.
CDKN2A/B co-deletion is associated with increased risk of local and distant intracranial recurrence after surgical resection of brain metastases
Authors: Morshed Ramin A , Nguyen Minh P , Cummins Daniel D , Saggi Satvir , Young Jacob S , Haddad Alexander F , Goldschmidt Ezequiel , Chang Edward F , McDermott Michael W , Berger Mitchel S , Theodosopoulos Philip V , Hervey-Jumper Shawn L , Daras Mariza , Aghi Manish K 
Published: January 2023

AbstractBackgroundWhile genetic alterations in brain metastases (BMs) have been previously explored, there are limited data examining their association with recurrence after surgical resection. This study aimed to identify genetic alterations within BMs associated with CNS recurrence after surgery across multiple cancer types.MethodsA retrospective, single-center study was conducted with patients who underwent resection of a BM with available clinical and gene sequencing data available. Local and remote CNS recurrence were the primary study outcomes. Next-generation sequencing of the coding regions in over 500 oncogenes was performed in brain metastasis specimens. Cox proportional hazards analyses were performed to identify clinical features and genomic alterations associated with CNS recurrence.ResultsA total of 90 patients undergoing resection of 91 BMs composed the cohort. Genes most frequently mutated in the cohort included TP53 (64%), CDKN2A (37%), TERT (29%), CDKN2B (23%), NF1 (14%), KRAS (14%), and PTEN (13%), all of which occurred across multiple cancer types. CDKN2A/B co-deletion was seen in 21 (23.1%) brain metastases across multiple cancer types. In multivariate Cox proportional hazard analyses including patient, tumor, and treatment factors, CDKN2A/B co-deletion in the brain metastasis was associated with increased risk of local (HR 4.07, 95% CI 1.32-12.54, P = 0.014) and remote (HR 2.28, 95% CI 1.11-4.69, P = 0.025) CNS progression. Median survival and length of follow-up were not different based on CDKN2A/B mutation status.ConclusionsCDKN2A/B co-deletion detected in BMs is associated with increased CNS recurrence after surgical resection. Additional work is needed to determine whether more aggressive treatment in patients with this mutation may improve outcomes.
Ending civil wars through fraudulent elections
Authors: Lehmann Michael Christian 
Published: January 2023

Abstract
Previous research finds a positive association between electoral fraud and post-election protests, violence, and civil conflict. This article contends that the effect of electoral fraud on peace can be heterogeneous. I investigate elections after civil wars that stalemated. My contribution is to present a theory and suggestive evidence that, in this context, electoral fraud by unpopular incumbents can be peace-promoting. An important policy implication is that international efforts to prevent electoral fraud (e.g. electoral observers), in this specific setting, may increase the odds that a civil war continues.
Brain Metastases from Biliary Tract Cancer: Case Series and Clinicogenomic Analysis
Authors: Dodoo Grace N , De Brian , Lee Sunyoung S , Abi Jaoude Joseph , Vauthey Jean-Nicolas , Tzeng Ching-Wei D , Tran Cao Hop S , Katlowitz Kalman A , Mandel Jacob J , Beckham Thomas H , Minsky Bruce D , Smith Grace L , Holliday Emma B , Koong Albert C , Das Prajnan , Taniguchi Cullen M , Javle Milind , Koay Eugene J , Ludmir Ethan B 
Published: January 2023

AbstractBackgroundLimited data from small series have suggested that brain metastases from biliary tract cancers (BrM-BTC) affect ≤2% of patients with BTC. We sought to review our experience with patients with BrM-BTC and to identify associations of tumor-related molecular alterations with outcomes.Materials and MethodsA retrospective review of patients with BTC seen at a tertiary referral center from 2005 to 2021 was performed; patients with BrM-BTC were identified, and clinical and molecular data were collected.ResultsTwenty-one of 823 patients with BTC (2.6%) developed BrM. For patients with BrM-BTC, median follow-up time was 27.9 months after primary BTC diagnosis and 3.1 months after BrM diagnosis. Median time from primary diagnosis to diagnosis of BrM was 14.4 [range, 1.1-66.0] months. Median overall survival (OS) from primary diagnosis was 31.5 [2.9-99.8] months and median OS from BrM diagnosis was 4.2 [0.2-33.8] months. Patients who underwent BrM-directed therapy trended toward longer OS following BrM diagnosis than patients receiving supportive care only (median 6.5 vs 0.8 months, P = .060). The BrM-BTC cohort was enriched for BRAF (30%), PIK3CA (25%), and GNAS (20%) mutations. patients with BrM-BTC with BRAF mutations trended toward longer OS following BrM diagnosis (median 13.1 vs 4.2 months, P = .131).ConclusionThis is the largest series of patients with BrM-BTC to date and provides molecular characterization of this rare subgroup of patients with BTC. Patients with BrM-BTC may be more likely to have BRAF mutations. With advances in targeted therapy for patients with BTC with actionable mutations, continued examination of shifting patterns of failure, with emphasis on BrM, is warranted.
Angular momentum inheritance from the Schwinger effect in (chromo)electromagnetic fields
Authors: Copinger Patrick , Hidaka Yoshimasa 
Published: January 2023

Abstract
The angular momentum of fermion pairs generated by the Schwinger effect is studied in homogeneous (chromo)electromagnetic fields, mimicking the early stages of a heavy-ion collision. It is demonstrated that the angular momentum density of produced pairs is proportional to that of the background fields. This is argued both heuristically in a virtual breaking condensate model by evaluating Wong’s equations, and out-of-equilibrium to one-loop using the in–in formalism.
FAM122A Is Required for Mesendodermal and Cardiac Differentiation of Embryonic Stem Cells
Authors: Yang Yun-Sheng , Liu Man-Hua , Yan Zhao-Wen , Chen Guo-Qiang , Huang Ying 
Published: January 2023

Abstract
Mesendodermal specification and cardiac differentiation are key issues for developmental biology and heart regeneration medicine. Previously, we demonstrated that FAM122A, a highly conserved housekeeping gene, is an endogenous inhibitor of protein phosphatase 2A (PP2A) and participates in multifaceted physiological and pathological processes. However, the in vivo function of FAM122A is largely unknown. In this study, we observed that Fam122 deletion resulted in embryonic lethality with severe defects of cardiovascular developments and significantly attenuated cardiac functions in conditional cardiac-specific knockout mice. More importantly, Fam122a deficiency impaired mesendodermal specification and cardiac differentiation from mouse embryonic stem cells but showed no influence on pluripotent identity. Mechanical investigation revealed that the impaired differentiation potential was caused by the dysregulation of histone modification and Wnt and Hippo signaling pathways through modulation of PP2A activity. These findings suggest that FAM122A is a novel and critical regulator in mesendodermal specification and cardiac differentiation. This research not only significantly extends our understanding of the regulatory network of mesendodermal/cardiac differentiation but also proposes the potential significance of FAM122A in cardiac regeneration.
Forty years (1980–2019) of visceral leishmaniasis in Nepal: trends and elimination challenges
Authors: Pandey Kishor , Dumre Shyam Prakash , Shah Yogendra , Acharya Bipin Kumar , Khanal Laxman , Pyakurel Uttam Raj , Kaneko Osamu , Pandey Basu Dev 
Published: January 2023

ABSTRACT

Background
Visceral leishmaniasis (VL) is an important re-emerging neglected tropical disease associated with poverty. Despite the elimination initiative started in 2005, VL cases have been expanding into geographic areas in Nepal. The present study aims at exploring the trends of VL from 1980 to 2019.

Methods
This retrospective analysis covers 40 y of VL cases reported by the Epidemiology Diseases Control Division, Nepal. Subgroup analyses for annual incidence were performed by age, sex, seasons, districts and provinces, and VL cases were visualized on in-country maps.

Results
A total of 34 564 cases and 584 deaths of VL were reported during 1980–2019. VL persistently increased until 2006 and was reported from all seven provinces of the country. The highest number of confirmed cases (n=2229) was reported in 2003 and the lowest (n=60) in 1983. VL cases expanded from 12 to 23 endemic districts. The key components of the VL elimination program are early diagnosis; enhanced surveillance; integrated vector management; social mobilization; research and treatment.

Conclusions
Expansion of VL towards the hilly and mountain regions of Nepal has posed challenges to the elimination program. Urgent VL control measures are required to achieve the elimination goals.
National Economic Conditions May Impact the Financial Barriers to Travel for Cancer Operations
Authors: Henry Leonard R. , Li Jun , Arciero Cletus , von Holzen Urs W. , Schwarz Roderich , Jatoi Ismail 
Published: January 2023

Background:
Better cancer-related outcomes are associated with physicians and hospitals with higher case volume. This serves as an incentive to refer patients requiring complex cancer operations to large referral centers, which may require increased travel for patients. However, barriers exist for patients to travel for cancer care, some of which may be aggravated or alleviated by factors relating to the health of the national economy. This impact may be reflected in variability of travel distances for cancer operations over time particularly for complex operation such as pancreatectomy and esophagectomy compared with less complex resections such as those for breast cancer or melanoma.

Methods:
We obtained the estimated travel distance for patients undergoing operations for cancer of the pancreas, esophagus, skin (melanoma), and breast from the National Cancer Database from 2004 to 2017 and correlated them with economic factors obtained from public sources. We then examined the impact of unemployment rates, gas prices, and inflation on travel distances regarding disadvantaged groups. Correlations were measured by the (rank-based, nonparametric) Spearman’s correlation coefficient, and the corresponding P value is obtained by the asymptotic distribution of the coefficient. A P value of 0.05 equates to an absolute correlation value of 0.532. To adjust for multiple tests, a more restrictive P value of 0.01 was also assessed, which equates to correlation coefficients of absolute value greater than 0.661.

Results:
There were 4,222,380 cases in the dataset, of which 1,781,056 remained after exclusion. The economic factors that were associated most strongly with the distance patients traveled for all cancer operation types were the labor force participation rate, personal savings, consumer price index, and changes in gasoline prices. Inflation and rising gasoline prices were often inversely related with travel distance in lower-income and less well-educated regions and African American patients.

Conclusions:
Several macroeconomic factors correlate with the travel distance for operations, suggesting that the economic health of the nation may aggravate or alleviate the financial barriers to travel for cancer operations. Financially disadvantaged groups may be particularly vulnerable to changes in gasoline prices and inflation. Organizations serving these populations may need to increase patient support services during times of economic hardship to avoid the exacerbation of health care disparities.
An Interesting Case of Severe Hyponatremia
Authors: Persons Jane E. , Stauffer Stephanie 
Published: January 2023

AbstractIn this report, we present an unusual and multifactorial case of severe hyponatremia with important clinical implications. The decedent was a 42-year-old woman who was discovered at her place of residence with altered mental status and profuse watery diarrhea. The scene was significant for numerous empty water bottles. She was transported to the emergency department of a local medical center and rapidly became obtunded. Imaging demonstrated cerebral edema with impending herniation. Serum chemistry was significant for severe hyponatremia (116 mEq/L) with decreased serum osmolality (245 mOsm/kg), suggestive of water overload. Over a brief course of hospitalization, she continued to deteriorate and brain death was pronounced. After brain death, she underwent organ donation. Subsequent autopsy examination demonstrated global cerebral edema with evidence of herniation. Toxicology examination of antemortem blood was positive for methamphetamine (1900 ng/mL) and amphetamine (100 ng/mL). An incidentally identified colon polyp was submitted for microscopic evaluation, which revealed the presence ofCryptosporidium, the likely cause of her diarrheal illness. Death was attributed to severe hyponatremia through the combined effects of excessive water consumption and loss of fluid and electrolytes from cryptosporidiosis, in turn leading to cerebral edema and brain herniation. Acute methamphetamine intoxication was a contributing condition.
Topical Anesthetic for Laceration Repair in Children
Authors: Jordan Faye , Spooner Louise 
Published: January 2023

Objective
The objective of this study is to evaluate the impact of the introduction of an education program familiarizing staff with the effective and appropriate use of Laceraine application to children’s lacerations requiring repair at The Prince Charles Hospital Children’s Emergency Department (TPCH-CED), Brisbane.

Methods
A retrospective audit was performed using data obtained from the local emergency department information system (EDIS) and a paper chart audit, for all presentations to TPCH-CED during 2015 and 2020 requiring laceration repair.

Results
Of the 20,813 registered patients to TPCH-CED in 2015, 993 (4.8%) required laceration repair, compared with 1756 (5.6%) of the 31,059 registered in 2020 demonstrating that presentations to the CED requiring laceration repair increased, as a proportion of overall presentations, reaching statistical significance across all groups (P < 0.001). The percentage of lacerations requiring repair that had Laceraine applied (either as a single agent or in combination) was 59% in 2015 and 93% in 2020 (P < 0.001). There was a significant increase in use of Laceraine only as agent of choice.

Conclusions
There was a significant change in practice with greater use of topical anesthetic (Laceraine) for the management of laceration repair of children, as expected, after the focused education program on its correct use. As emergency departments continue to be overwhelmed with increasing attendances and long patient wait times, a simple small intervention, such as that described, has potential to improve flow through the children's emergency department. Future research should focus on a randomized control trial to determine the contribution of the use of a topical agent, as opposed to injectable local anesthetic and/or full procedural sedation to determine the contribution to the impact of this simple change of practice on patient flow and satisfaction.
Adherence to the New Zealand Pediatric Guideline for the Assessment and Diagnosis of Inflammatory Bowel Disease
Authors: Martin Natalie G. , Roberts Amin J. , Evans Helen M. , Bishop Jonathan , Day Andrew S. 
Published: January 2023

Background:
New Zealand (NZ) guidelines for the approach to diagnosis and management of inflammatory bowel disease (IBD) in children were developed in 2014.

Objectives:
This study aimed to assess the application of the guidelines in a group of children diagnosed with IBD in regards to baseline investigations.

Methods:
This retrospective observational study analyzed the application of recommended baseline investigations included in the NZ guidelines in a group of children aged <16 years diagnosed consecutively with IBD at the 2 NZ tertiary pediatric gastroenterology centers.

Results:
Fifty children were included from each center. Seventy-two were diagnosed with Crohn’s disease (CD), 15 with ulcerative colitis (UC), and 13 were with IBD unclassified. The children with CD had a mean Pediatric Crohn’s Disease Activity Index score of 31 and almost half had ileocolonic involvement (47%). The 15 children with UC had a mean PUCAI score of 42, and 13 had pancolonic involvement. All 100 children underwent upper and lower gastrointestinal endoscopy with biopsies, and 92% had magnetic resonance enterography at diagnosis. Iron studies, folate, and vitamin B12 were measured in >70 children. Serum zinc, magnesium, and phosphate were infrequently measured. Current anthropometry was recorded in all children but historical growth data were variably recorded. Vaccination status was also inconsistently recorded.

Conclusion:
Most of this group of children diagnosed with IBD in 2 NZ centers underwent key recommended investigations at diagnosis including gastrointestinal endoscopy and small bowel imaging. Other baseline assessments, including measurement of micronutrient levels, were completed variably. Measures to enhance consistent baseline assessments are required.