bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pancreatic Cancer Surveillance and Survival of High-Risk Individuals
Authors: Blackford Amanda L. , Canto Marcia Irene , Dbouk Mohamad , Hruban Ralph H. , Katona Bryson W. , Chak Amitabh , Brand Randall E. , Syngal Sapna , Farrell James , Kastrinos Fay , Stoffel Elena M. , Rustgi Anil , Klein Alison P. , Kamel Ihab , Fishman Elliot K. , He Jin , Burkhart Richard , Shin Eun Ji , Lennon Anne Marie , Goggins Michael 
Published: July 2024

ImportancePancreatic ductal adenocarcinoma (PDAC) is a deadly disease with increasing incidence. The majority of PDACs are incurable at presentation, but population-based screening is not recommended. Surveillance of high-risk individuals for PDAC may lead to early detection, but the survival benefit is unproven.ObjectiveTo compare the survival of patients with surveillance-detected PDAC with US national data.Design, Setting, and ParticipantsThis comparative cohort study was conducted in multiple US academic medical centers participating in the Cancer of the Pancreas Screening program, which screens high-risk individuals with a familial or genetic predisposition for PDAC. The comparison cohort comprised patients with PDAC matched for age, sex, and year of diagnosis from the Surveillance, Epidemiology, and End Results (SEER) program. The Cancer of the Pancreas Screening program originated in 1998, and data collection was done through 2021. The data analysis was performed from April 29, 2022, through April 10, 2023.ExposuresEndoscopic ultrasonography or magnetic resonance imaging performed annually and standard-of-care surgical and/or oncologic treatment.Main Outcomes and MeasuresStage of PDAC at diagnosis, overall survival (OS), and PDAC mortality were compared using descriptive statistics and conditional logistic regression, Cox proportional hazards regression, and competing risk regression models. Sensitivity analyses and adjustment for lead-time bias were also conducted.ResultsA total of 26 high-risk individuals (mean [SD] age at diagnosis, 65.8 [9.5] years; 15 female [57.7%]) with PDAC were compared with 1504 SEER control patients with PDAC (mean [SD] age at diagnosis, 66.8 [7.9] years; 771 female [51.3%]). The median primary tumor diameter of the 26 high-risk individuals was smaller than in the control patients (2.5 [range, 0.6-5.0] vs 3.6 [range, 0.2-8.0] cm, respectively; P &amp;lt; .001). The high-risk individuals were more likely to be diagnosed with a lower stage (stage I, 10 [38.5%]; stage II, 8 [30.8%]) than matched control patients (stage I, 155 [10.3%]; stage II, 377 [25.1%]; P &amp;lt; .001). The PDAC mortality rate at 5 years was lower for high-risk individuals than control patients (43% vs 86%; hazard ratio, 3.58; 95% CI, 2.01-6.39; P &amp;lt; .001), and high-risk individuals lived longer than matched control patients (median OS, 61.7 [range, 1.9-147.3] vs 8.0 [range, 1.0-131.0] months; 5-year OS rate, 50% [95% CI, 32%-80%] vs 9% [95% CI, 7%-11%]).Conclusions and RelevanceThese findings suggest that surveillance of high-risk individuals may lead to detection of smaller, lower-stage PDACs and improved survival.
Adjuvant Gemcitabine Plus Cisplatin and Chemoradiation in Patients With Gallbladder Cancer
Authors: Ostwal Vikas , Patkar Shraddha , Engineer Reena , Parulekar Manali , Mandavkar Sarika , Bhargava Prabhat , Srinivas Sujay , Krishnatry Rahul , Gudi Shivakumar , Kapoor Akhil , Pandey Durgatosh , Patel Swapnil , Singhal Abhishek , Goel Alok , Dora Tapas Kumar , Chaudhary Debashish , Chaugule Deepali , Naughane Deepali , Daddi Anuprita , Patil Rajshree , Ankathi Suman Kumar , Ramaswamy Anant , Goel Mahesh 
Published: July 2024

ImportanceThere is limited evidence with regard to the benefit of adjuvant chemotherapy chemoradiotherapy in resected gallbladder cancers (GBCs).ObjectiveTo establish a baseline survival rate for operated GBCs in patients receiving either gemcitabine plus cisplatin (GC) or capecitabine and capecitabine concurrent with chemoradiation (CCRT).Design, Setting, and ParticipantsThe GECCOR-GB study was a multicenter, open-label, randomized phase 2 noncomparator “pick the winner” design trial of adjuvant GC and CCRT in patients with resected histologically confirmed adenocarcinoma or adenosquamous carcinoma of the gallbladder, (stage II/III) with no local residual tumor (R0) or microscopic residual tumor (R1). The study was carried out in 3 tertiary cancer institutions in India. Patients 18 years or older with adequate end-organ functions, and Eastern Cooperative Oncology Group Performance Status of 1 or lower between May 2019 and February 2022 were enrolled. The cutoff date for data analysis was February 28, 2023.InterventionsPatients were randomized 1:1 to receive either GC every 3 weeks (maximum of 6 cycles) or CCRT comprising capecitabine with concurrent chemoradiation (capecitabine concurrent with radiotherapy) sandwiched between capecitabine chemotherapy.Main Outcomes and MeasuresThe primary outcome was disease-free survival (DFS) at 1 year in randomized patients. This study was conducted as 2 parallel, single-stage phase 2 clinical trials. Within each treatment arm, a 1-year DFS rate of less than 59% was considered as insufficient activity, whereas a 1-year DFS rate of 77% or higher would be considered as sufficient activity.ResultsWith a median follow-up of 23 months, 90 patients were randomized, 45 in each arm. Overall, there were 31 women (69%) and 14 men (31%) in the GC arm with a mean (range) age of 56 (33-72) years and 34 women (76%) and 11 men (24%) in the CCRT group with a mean (range) age of 55 (26-69) years. In the GC and CCRT arms, 1-year DFS and estimated 2-year DFS was 88.9% (95% CI, 79.5-98.3) and 74.8% (95% CI, 60.4-89.2), and 77.8% (95% CI, 65.4-90.2) and 74.8% (95% CI, 59.9-86.3), respectively. Completion rates for planned treatment was 82% in the GC arm and 62% in the CCRT arm.Conclusions and RelevanceIn this randomized clinical trial, GC and CCRT crossed the prespecified trial end points of 1-year DFS in patients with resected stage II/III GBCs. The results set a baseline for a larger phase 3 trial evaluating both regimens in operated GBCs.Trial RegistrationClinicalTrials.gov Identifier: CTRI/2019/05/019323I
Obesity and Survival After Immune Checkpoint Inhibition for Head and Neck Squamous Cell Carcinoma
Authors: Mastrolonardo Eric V. , Llerena Pablo , Lu Joseph , Nunes Kathryn , Choi Grace K. , Amin Dev , Bridgham Kelly M. , Campbell Daniel , Philips Ramez , Cognetti David M. , Luginbuhl Adam J. , Curry Joseph M. 
Published: July 2024

ImportanceFor patients treated with immune checkpoint inhibitors (ICIs), recent data suggest that obesity has a beneficial effect on survival outcomes in various cancer types. Reports on this association in head and neck cancer are limited.ObjectivesTo compare overall survival (OS) to 5 years and functional outcomes in patients with head and neck squamous cell carcinoma (HNSCC) treated with ICIs based on pretreatment body mass index (BMI).Design, Setting, and ParticipantsThis retrospective population-based cohort study used data obtained from the TriNetX Global Collaborative Network database to identify patients with HNSCC who received ICI treatment between January 1, 2012, and December 31, 2023, resulting in a total of 166 patients (83 with BMI of 20.0-24.9 [normal BMI] and 83 with BMI of ≥30.0 [obesity BMI]) after propensity score matching (PSM) for pretreatment medical comorbidities and oncologic staging.ExposureNormal BMI vs obesity BMI.Main Outcomes and MeasuresOverall survival and functional outcomes (dysphagia, tracheostomy dependence, and gastrostomy tube dependence) were measured to 5 years after ICI treatment and compared between patients with obesity BMI and normal BMI. Additional analyses compared OS and functional outcomes in the cohort with normal BMI and cohorts with overweight BMI (25.0-29.9) and underweight BMI (&amp;lt;20.0).ResultsAmong the 166 patients included in the PSM analysis (112 men [67.1%]; mean [SD] age, 62.9 [15.4] years), obesity BMI was associated with significantly improved OS at 6 months (hazard ratio [HR], 0.54 [95% CI, 0.31-0.96]), 3 years (HR, 0.56 [95% CI, 0.38-0.83]), and 5 years (HR, 0.62 [95% CI, 0.44-0.86]) after ICI treatment, compared with patients with normal BMI. Obesity BMI was also associated with decreased risk of gastrostomy tube dependence at 6 months (odds ratio [OR], 0.41 [95% CI, 0.21-0.80]), 1 year (OR, 0.41 [95% CI, 0.21-0.78]), 3 years (OR, 0.35 [95% CI, 0.18-0.65]), and 5 years (OR, 0.34 [95% CI, 0.18-0.65]). Obesity was also associated with decreased risk for tracheostomy dependence at 1 year (OR, 0.52 [95% CI, 0.28-0.90]), 3 years (OR, 0.45 [95% CI, 0.45-0.90]), and 5 years (OR, 0.45 [95% CI, 0.45-0.90]). There were no differences in rates of dysphagia or immune-related adverse events between cohorts at any points.Conclusions and RelevanceUsing population-level data for patients with HNSCC treated with ICIs, these results suggest that having obesity was associated with improved 6-month, 3-year, and 5-year OS compared with having normal BMI. Additionally, obesity was associated with decreased gastrostomy and tracheostomy tube dependence compared with normal BMI. Further investigation is required to understand the mechanism of these findings.
Gratitude and Mortality Among Older US Female Nurses
Authors: Chen Ying , Okereke Olivia I. , Kim Eric S. , Tiemeier Henning , Kubzansky Laura D. , VanderWeele Tyler J. 
Published: July 2024

ImportanceSupporting healthy aging is a US public health priority, and gratitude is a potentially modifiable psychological factor that may enhance health and well-being in older adults. However, the association between gratitude and mortality has not been studied.ObjectiveTo examine the association of gratitude with all-cause and cause-specific mortality in later life.Design, Setting, and ParticipantsThis population-based prospective cohort study used data from self-reported questionnaires and medical records of 49 275 US older female registered nurses who participated in the Nurses’ Health Study (2016 questionnaire wave to December 2019). Cox proportional hazards regression models estimated the hazard ratio (HR) of deaths by self-reported levels of gratitude at baseline. These models adjusted for baseline sociodemographic characteristics, social participation, physical health, lifestyle factors, cognitive function, and mental health. Data analysis was conducted from December 2022 to April 2024.ExposureGratitude was assessed with the 6-item Gratitude Questionnaire, a validated and widely used measure of one’s tendency to experience grateful affect.Main Outcomes and MeasuresDeaths were identified from the National Death Index, state statistics records, reports by next of kin, and the postal system. Causes of death were ascertained by physicians through reviewing death certificates and medical records.ResultsAmong the 49 275 participants (all female; mean [SD] age at baseline, 79 [6.16] years), 4608 incident deaths were identified over 151 496 person-years of follow-up. Greater gratitude at baseline was associated with a lower hazard of mortality in a monotonic fashion. For instance, the highest tertile of gratitude, compared with the lowest tertile, was associated with a lower hazard of all-cause deaths (HR, 0.91; 95% CI, 0.84-0.99) after adjusting for baseline sociodemographic characteristics, social participation, religious involvement, physical health, lifestyle factors, cognitive function, and mental health. When considering cause-specific deaths, death from cardiovascular disease was inversely associated with gratitude (HR, 0.85; 95% CI, 0.73-0.995).Conclusions and RelevanceThis study provides the first empirical evidence suggesting that experiencing grateful affect is associated with increased longevity among older adults. The findings will need to be replicated in future studies with more representative samples.
Biliary Dyskinesia—Controversies, Diagnosis, and Management
Authors: Richmond Bryan K. 
Published: July 2024

ImportanceBiliary dyskinesia is a disorder characterized by biliary pain, a sonographically normal gallbladder, and a reduced gallbladder ejection fraction on cholecystokinin-cholescintigraphy (CCK-HIDA) scan. Laparoscopic cholecystectomy remains a common treatment for biliary dyskinesia despite a lack of high-quality evidence supporting the practice. The following review summarizes the current biliary dyskinesia outcomes data, the diagnostic strategies and their limitations, biliary dyskinesia in the pediatric population, the emerging phenomenon of the hyperkinetic gallbladder, and suggestions for addressing identified knowledge gaps.ObservationsThe majority of studies on the topic are retrospective, with wide variations in inclusion criteria and definition of biliary pain. Most report a very short follow-up interval, often a single office visit, with variable and nonstandardized definitions of a satisfactory outcome. Despite a published Society of Nuclear Medicine guideline for its performance, CCK-HIDA scan protocols vary among institutions, which has led to considerable variability in the consistency and reproducibility of CCK-HIDA results. The few prospective studies available, although small and heterogeneous, support a role for cholecystectomy in the treatment of adult biliary dyskinesia. Despite these knowledge gaps, biliary dyskinesia is now the number 1 indication for cholecystectomy in children. Cholecystectomy for the hyperkinetic gallbladder appears to be an emerging phenomenon, despite, as in biliary dyskinesia, a lack of quality data supporting this practice. Randomized trials addressing these gaps are needed but have been difficult to conduct owing to strong clinician and patient bias toward surgery and the lack of a criterion-standard nonsurgical treatment for the control arm.Conclusions and RelevanceThe use of cholecystectomy for adult biliary dyskinesia is reasonable based on the available data. Insufficient data exist regarding laparoscopic cholecystectomy for pediatric dyskinesia and the hyperkinetic gallbladder population. Large-scale prospective studies, either randomized trials or large prospectively followed cohort studies, are needed to address the knowledge gaps surrounding this controversial diagnosis.
Gastric Bypass vs Diet and Cardiovascular Risk Factors
Authors: Karlsson Cecilia , Johnson Line Kristin , Greasley Peter J. , Retterstøl Kjetil , Hedberg Jonatan , Hall Martin , Hawker Noele , Robertsen Ida , Havsol Jesper , Hertel Jens Kristoffer , Sandbu Rune , Skovlund Eva , Olsen Thomas , Christensen Hege , Jansson-Löfmark Rasmus , Andersson Shalini , Åsberg Anders , Hjelmesæth Jøran 
Published: July 2024

ImportanceRoux-en-Y gastric bypass (RYGB) is associated with reduced cardiovascular (CV) risk factors, morbidity, and mortality. Whether these effects are specifically induced by the surgical procedure or the weight loss is unclear.ObjectiveTo compare 6-week changes in CV risk factors in patients with obesity undergoing matching caloric restriction and weight loss by RYGB or a very low-energy diet (VLED).Design, Setting, and ParticipantsThis nonrandomized controlled study (Impact of Body Weight, Low Calorie Diet, and Gastric Bypass on Drug Bioavailability, Cardiovascular Risk Factors, and Metabolic Biomarkers [COCKTAIL]) was conducted at a tertiary care obesity center in Norway. Participants were individuals with severe obesity preparing for RYGB or a VLED. Recruitment began February 26, 2015; the first patient visit was on March 18, 2015, and the last patient visit (9-week follow-up) was on August 9, 2017. Data were analyzed from April 30, 2021, through June 29, 2023.InterventionsVLED alone for 6 weeks or VLED for 6 weeks after RYGB; both interventions were preceded by 3-week LED.Main Outcomes and MeasuresBetween-group comparisons of 6-week changes in CV risk factors.ResultsAmong 78 patients included in the analyses, the mean (SD) age was 47.5 (9.7) years; 51 (65%) were women, and 27 (35%) were men. Except for a slightly higher mean (SD) body mass index of 44.5 (6.2) in the RYGB group (n = 41) vs 41.9 (5.4) in the VLED group (n = 37), baseline demographic and clinical characteristics were similar between groups. Major atherogenic blood lipids (low-density lipoprotein cholesterol, non–high-density lipoprotein cholesterol, apolipoprotein B, lipoprotein[a]) were reduced after RYGB in comparison with VLED despite a similar fat mass loss. Mean between-group differences were −17.7 mg/dL (95% CI, −27.9 to −7.5), −17.4 mg/dL (95% CI, −29.8 to −5.0) mg/dL, −9.94 mg/dL (95% CI, −15.75 to −4.14), and geometric mean ratio was 0.55 U/L (95% CI, 0.42 to 0.72), respectively. Changes in glycemic control and blood pressure were similar between groups.Conclusions and RelevanceThis study found that clinically meaningful reductions in major atherogenic blood lipids were demonstrated after RYGB, indicating that RYGB may reduce CV risk independent of weight loss.Trial RegistrationClinicalTrials.gov Identifier: NCT02386917
EPHB2 Knockdown Mitigated Myocardial Infarction by Inhibiting MAPK Signaling
Authors: Jiang Xiaoyan , Wang Wenhua , Kang Haofei 
Published: July 2024

AbstractMyocardial infarction (MI) is a common type of cardiovascular disease. The incidence of ventricular remodeling dysplasia and heart failure increases significantly after MI. The objective of this study is to investigate whether erythropoietin hepatocellular receptor B2 (EPHB2) can regulate myocardial injury after MI and explore its regulatory pathways. EPHB2 is significantly overexpressed in the heart tissues of MI mice. The downregulation of EPHB2 alleviates the cardiac function damage after MI. Knockdown EPHB2 alleviates MI‐induced myocardial tissue inflammation and apoptosis, and myocardial fibrosis in mice. EPHB2 knockdown significantly inhibits the activation of mitogen activated kinase‐like protein (MAPK) pathway in MI mice. Moreover, EPHB2 overexpression significantly promotes the phosphorylation of MAPK pathway‐related protein, which can be reversed by MAPK‐IN‐1 (an MAPK inhibitor) treatment. In conclusion, silencing EPHB2 can mitigate MI‐induced myocardial injury by inhibiting MAPK signaling in mice, suggesting that targeting EPHB2 can be a promising therapeutic target for MI‐induced myocardial injury.
PLD‐Grown Semi‐Insulating Ga2O3 Thin Film‐Based Optoelectronic Artificial Synaptic Devices for Neuromorphic Computing Applications
Authors: Kaur Amandeep , Sikdar Subhrajit , Yadav Santosh Kumar , Dhar Subhabrata 
Published: July 2024

AbstractDevelopment of artificial opto‐electronic synaptic devices plays a crucial role for the practical implementation of energy‐efficient, parallel processing of human brain. In this article, two terminal inter‐digitated devices are fabricated on Gallium oxide (Ga2O3) thin films grown on sapphire substrates by pulsed laser deposition (PLD) technique to study its ability to mimic biological synaptic behaviors. The layers are found to exhibit long persistent photo‐conductivity (PPC) effect, which is identified to be the key parameter to replicate the behavior of biological synapses. Channel resistance and PPC time constants should also be optimized to improve the efficiency of response and energy consumption of synaptic devices. It has been observed that both conductivity and the PPC decay time of Ga2O3‐films can be controlled by varying oxygen pressure and growth temperature (TG). These devices demonstrate their ability to perform paired pulse facilitation (PPF) at very low applied bias in mV‐range. They can mimic biological synapses showing short‐to‐long‐term memory transition (STM‐to‐LTM) and learning‐forgetting behavior. One of these devices is found to show synaptic behavior with the energy consumption of as low as 71fJ electrical and 21nJ optical per synaptic event. These findings thus strengthen the candidature of Ga2O3 films for the development of next‐generation opto‐electronic neuromorphic devices and systems.
Accessing 2‐(Chalcogen)benzothiazoles via Electrochemical Intermolecular Cyclization of Isocyanides with Thiols or Diselenides
Authors: Zhang Yi , Mo Zu‐Yu , Tang Xin‐Yu , Tang Hai‐Tao , Pan Ying‐Ming , Yang Ke‐Di , Huang Yong‐Lin , He Mu‐Xue 
Published: July 2024

Abstract2‐(chalcogen)benzothiazoles are frequently used as core structures for the development of pharmaceutical agents. A strategy for the synthesis of 2‐(chalcogen)benzothiazoles under electrooxidative conditions using isocyanides, thiols or diselenides as substrates was developed. This protocol allows access to structurally diverse 2‐(chalcogen)benzothiazoles in good yields and with good functional group tolerance, which does not require heavy metal catalysts and exogenous oxidants. Furthermore, gram‐scale synthesis was performed to demonstrate the scale‐up applicability of this reaction.
EBV‐positive diffuse large B‐cell lymphoma, not otherwise specified: 2024 update on the diagnosis, risk‐stratification, and management
Authors: Malpica Luis , Marques‐Piubelli Mario L. , Beltran Brady E. , Chavez Julio C. , Miranda Roberto N. , Castillo Jorge J. 
Published: July 2024

AbstractDisease overviewEpstein Barr virus‐positive (EBV+) diffuse large B‐cell lymphoma (DLBCL), not otherwise specified (NOS) is an aggressive B‐cell lymphoma associated with EBV infection included in the WHO classification of lymphoid neoplasms since 2016. Although historically associated to poor prognosis, outcomes seem to have improved in the era of chemoimmunotherapy.DiagnosisThe diagnosis is established through meticulous pathological evaluation. Detection of EBV‐encoded RNA (EBER) is the standard diagnostic method. The ICC 2022 specifies EBV+ DLBCL, NOS as occurring when >80% of malignant cells express EBER, whereas the WHO‐HAEM5 emphasizes that the majority of tumor cells should be EBER positive without setting a defined threshold. The differential diagnosis includes plasmablastic lymphoma, DLBCL associated with chronic inflammation, primary effusion lymphoma, among others.Risk‐stratificationThe International Prognostic Index (IPI) and the Oyama score can be used for risk‐stratification. The Oyama score includes age >70 years and presence of B symptoms. The expression of CD30 and PD‐1/PD‐L1 are emerging as potential adverse but targetable biomarkers.ManagementPatients with EBV+ DLBCL, NOS, should be staged and managed following similar guidelines than patients with EBV‐negative DLBCL. EBV+ DLBCL, NOS, however, might have a worse prognosis than EBV‐negative DLBCL in the era of chemoimmunotherapy. Therefore, inclusion of patients in clinical trials when available is recommended. There is an opportunity to study and develop targeted therapy in the management of patients with EBV+ DLBCL, NOS.