bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation of safety and efficacy of atezolizumab therapy across indications
Authors: Durán-Pacheco Gonzalo , Chandler G Scott , Maiya Vidya , Socinski Mark A , Sonpavde Guru , Puente Javier , Essioux Laurent , Carter Corey , Cardona Jose Vicente , Mohindra Rajat , Naidoo Jarushka 
Published: November 2024

BackgroundThe association between safety and efficacy of immune checkpoint inhibitors is known, but the correlation between severity and impact of specific organ involvement by immune-related adverse events (irAE) and cancer outcomes is poorly understood. Most irAEs are mild-to-moderate but severe irAEs may pose clinical management challenges and affect patient outcomes.MethodsWe assessed the association between irAE grade (G) and specific organ involvement with overall survival (OS) in 9,521 patients across 14 studies involving atezolizumab as mono (IO) or with chemo/targeted (C-IO) therapy as compared with chemo/targeted therapy (C) in advanced non-small cell lung, small-cell lung, renal cell, urothelial, and triple-negative breast cancers. We used a mixed-effect Cox proportional hazard model for time-varying covariates to address immortal-time bias; adjusted for baseline factors associated with irAEs and OS to control for confounding bias; and focused on five common irAEs (dermatologic, thyroid dysfunction, hepatitis, pneumonitis, and colitis) to avoid low statistical power for rare events.ResultsFor patients treated with IO or C-IO, G1-2 irAEs were associated with improved OS (HR=0.65, p<0.01) and G3-4 irAEs showed a slight increased risk of death (HR=1.18, p=0.10) versus patients without irAEs. By specific irAE, G1-2 cutaneous irAEs, thyroid dysfunction, or pneumonitis were associated with improved OS (p<0.05), while G3-4 pneumonitis and colitis were associated with worse OS (p<0.01). There was no association between hepatitis and OS by any grade. Findings were consistent across indications.ConclusionsThis analysis demonstrates a correlation between irAEs and improved OS with atezolizumab by severity grade and the most common irAEs by organ involvement. Low-grade irAEs are significantly associated with improved OS, while specific high-grade irAEs are associated with poorer OS, underscoring the importance of early recognition and management of toxicity to optimize benefit/risk balance.
Is rheumatoid arthritis always preceded by a symptomatic at-risk phase of arthralgia?
Authors: Claassen Stijn , Boeren Anna M P , Khidir Sarah J H , van Steenbergen Hanna W , van der Helm-van Mil Annette H M 
Published: November 2024

ObjectivesSecondary prevention of rheumatoid arthritis (RA) is generally considered potentially impactful because the entire RA population is believed to experience a symptomatic ‘pre-RA’ phase. We wondered whether this dogma is correct. Therefore we investigated an inception cohort of patients with newly diagnosed RA and studied among them patients who did and did not present with preceding arthralgia at risk for RA.MethodsConsecutively diagnosed patients with RA between 2012 and 2022 were studied (n=699). These patients had either directly presented with clinically apparent arthritis, or had first presented with clinically suspect arthralgia (CSA). Clinical characteristics at symptom onset and RA diagnosis were compared. Whether certain characteristics frequently occurred together was studied using a K-means algorithm after dimension reduction with partial least squares discriminant analysis. To validate that groups differed in long-term outcomes, sustained disease-modifying anti-rheumatic drug-free remission (SDFR) of the groups was studied during a median follow-up of 5.3 years.ResultsPatients with RA who had first presented with CSA were younger, more often had a gradual symptom onset and were more often anti-citrullinated protein antibodies (ACPA)-positive. Studying characteristics at symptom onset and RA diagnosis revealed four patient clusters, of which two clusters included almost all patients with a preceding CSA phase. Patients in these two clusters (55% of RA population) were younger, had a gradual symptom onset, longer symptom duration and were more frequently ACPA-positive. Patients with RA in these clusters achieved SDFR less often (HR 0.51 (95% CI 0.37 to 0.68)) than the patients with RA in the two clusters where preceding CSA was infrequent/absent.ConclusionThese data suggest the notion that the entire RA population has an identifiable symptomatic risk stage should be refuted. This may impact on the scope of preventive interventions targeting the symptomatic risk phase.
Partial involvement of nitric oxide synthase in increased pilocarpine-induced sweating in exercise-trained men
Authors: Okamoto Yumi , Otsuka Junto , Amano Tatsuro 
Published: November 2024

The physiological mechanisms involved in augmented cholinergic agonist-induced sweating in exercise-trained individuals remain unclear. This study hypothesizes that nitric oxide synthase (NOS) contributes to augmented pilocarpine-induced sweating in habitually exercise-trained individuals. Endurance-trained and untrained men ( n = 15 each) iontophoretically received 1% L-NAME, a NOS inhibitor, and saline (control) in the forearm and then administered 0.001% and 1% pilocarpine to evaluate sweat rate. L-NAME administration attenuated pilocarpine-induced sweating by 10% in the exercise-trained ( P = 0.004) but not in untrained ( P = 0.764) groups independent of pilocarpine concentrations. Results indicate that NOS partially contributes to increased cholinergic sweating in exercise-trained men.
Comparison of Hand Function after Single-Digit Replantation in Elderly and Younger Patients
Authors: NAKANISHI Akito , KAWAMURA Kenji , OMOKAWA Shohei , HASEGAWA Hideo , TANAKA Yasuhito 
Published: November 2024

Background: With ageing of the population, there is an increasing likelihood that elderly people will seek employment, with a resultant increase in the incidence of hand injuries, including digital amputations. However, the surgical indication for replantation of an amputated digit in elderly patients is controversial. The purpose of this study was to compare functional outcomes after single-digit replantation of the thumb to long finger in older (≥65 years old) and younger (<65 years old) patients to assess the feasibility of digit replantation in the elderly population. Methods: A retrospective cohort study was performed in 25 patients (12 elderly and 13 younger) with successful replantation of the thumb, index or long finger at our hospital. All patients were followed up for more than 1 year. Key pinch strength, Semmes–Weinstein (S–W) test, % total active motion (TAM), Purdue Pegboard Test score (hand dexterity) and Disabilities of the Arm, Shoulder and Hand (DASH) score were investigated. Results: Elderly patients showed significantly worse results for the S–W test and Purdue Pegboard Test score. The % TAM, key-pinch strength and DASH scores were similar in the two groups. Conclusions: Replantation surgery in elderly patients results in similar postoperative hand function (finger mobility and pinch strength) and activities of daily living to those in younger patients. Level of Evidence: Level III (Therapeutic)
ATP: Achieving Throughput Peak for DNN Training via Smart GPU Memory Management
Authors: Chen Weiduo , Dong Xiaoshe , Zhang Fan , Li Bowen , Wang Yufei , Wang Qiang 
Published: November 2024

Due to the limited GPU memory, the performance of large DNNs training is constrained by the unscalable batch size. Existing researches partially address the issue of GPU memory limit through tensor recomputation and swapping, but overlook the exploration of optimal performance.
In response, we propose ATP, a recomputation and swapping based GPU memory management framework that aims to maximize training performance by breaking GPU memory constraints. ATP utilizes a throughput model we proposed to evaluate the theoretical peak performance achievable by DNN training on GPU, and provide the optimum memory size required for recomputation and swapping. We optimize the mechanisms for GPU memory pool and CUDA stream control, employs an optimization method to search for specific tensors requiring recomputation and swapping, thereby bringing the actual DNN training performance on ATP closer to theoretical values. Evaluations with different types of large DNN models indicate that ATP achieve throughput improvements ranging from 1.14 ∼ 1.49 ×, while support model training exceeding the GPU memory limit by up to 9.2 ×.
Construction of Mo-Doped CuO Incorporated on Carbon Black Modified Disposable Sensor for the Voltammetric Detection of Metol in Environmental Samples
Authors: Sivaji Saravana Pandi , Rex Shanlee Santhiyagu Sahayaraj , Chen Tse-Wei , Chen Shen-Ming , Elayappan Tamilalagan , Al-onazi Wedad A. , Ali M. Ajmal , S. Elshikh Mohamed , Ravikumar Mekatharseni 
Published: November 2024

In this study, a molybdenum-doped copper oxide (Mo–CuO) composite was synthesized via a hydrothermal method and combined with carbon black (CB) to form Mo–CuO@CB. This composite was used to modify a screen-printed carbon electrode (SPCE) for the detection of Metol (MT), an industrial pollutant harmful to both human health and the environment. Structural and surface characterization was performed using high-resolution transmission electron microscopy, field-effect scanning electron microscopy, energy-dispersive spectroscopy, Raman spectroscopy, X-ray photoelectron spectroscopy, and X-ray diffraction. Electrochemical techniques, including differential pulse voltammetry and cyclic voltammetry, were used to assess the sensor’s performance. The Mo–CuO@CB@SPCE sensor exhibited a low detection limit of 2.7 nM, and limit of quantification is 82 nM, a broad linear range (5.0 × 10−9–170 mol L−1), and high sensitivity (4.148 μA μM−1 cm−2), benefiting from the catalytic activity of Mo–CuO and the large surface area of CB. With recovery rates ranging from 96% to 100.6% in pond, river, and tap water, the sensor effectively detects MT in environmental samples, ensuring reliable monitoring of this persistent pollutant.
Abstract B021: tRNA fragments extracted from patient plasma extra cellular vesicles display potential as biomarkers for high-grade glioma
Authors: Phinney Thomson R , Alwadei Ali , Wajnberg Gabriel Gabriel , Han Jae , Chacko Simi , Attwood Kathleen , Roy Jeremy , Weeks Adriennne 
Published: November 2024

Abstract
Transfer RNA (tRNA) are non-coding RNAs that bring amino acids to ribosomes during translation. Recent studies have shown that cleaved fragments derived from tRNA (tRFs) serve regulatory roles in epigenetics, signaling, transcription, and translation. tRFs can be released from cells and can be found in extracellular vesicles to perform some aspects of paracrine signaling. Utilizing high throughput small RNA sequencing, we have identified over 750 uniquely or multi-mapped (6.9% of total sRNA mapped reads) tRFs in extracellular vesicles of high-grade glioma (IDH-WT) patient plasma. By performing differential expression analysis, we identified 6 upregulated tRFs and 36 downregulated tRFs between high-grade glioma plasma EVs and non-cancer controls (n = 14, FDR&lt;0.05). Differentially expressed tRFs (all 42) were further analyzed using bioinformatic techniques (RNAhybrid and IntaRNA) to predict potential gene targets. By performing gene ontology analysis (ShinyGO) we found that 70 of 75 genes related to glioma formation were identified as potential gene targets, indicating a possible role of tRFs in the regulation and formation of gliomas. A number of differentially expressed tRFs were predicted to target cancer-related genes including Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT-1). This analysis demonstrates that tRFs may serve as important biomarkers and regulators with therapeutic potential in the future
Citation Format: Thomson R Phinney, Ali Alwadei, Gabriel Gabriel Wajnberg, Jae Han, Simi Chacko, Kathleen Attwood, Jeremy Roy, Adriennne Weeks. tRNA fragments extracted from patient plasma extra cellular vesicles display potential as biomarkers for high-grade glioma [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B021.
Abstract B026: Glioblastoma multiforme disseminates outside the central nervous system
Authors: Stejskal Pavel , Srovnal Josef , Rehulkova Alona , Kalita Ondrej , Slachta Marek , Hajduch Marian 
Published: November 2024

Abstract
Introduction: The liquid biopsy (LB) concept has gained significant attention in the last decade and has the potential to revolutionize cancer care. However, more validation in clinical trials is required on the value of LB in medical settings. Here, we focus on glioblastoma multiforme (GBM), a highly invasive and fatal subtype of the central nervous system malignant tumors. Circulating tumor cells (CTCs) are primary tumor cells released into the peripheral blood and migrating to distant organs. CTC presence is related to tumor spread and recurrence. In GBM, factors like short patient survival, the blood-brain barrier (BBB), and lack of lymphatic drainage in brain tissue make systemic dissemination rare but possible. Thus, noninvasive CTC detection can hold potential for diagnostic, predictive, and prognostic applications. Material and Methods: For cell stability preservation before sample processing, the peripheral blood samples from curatively resected GBM patients were collected preoperatively in Cell-Free DNA BCT® tubes (Streck, Inc.). CTCs were identified using CytoTrack CT11TM (2/C), a semi-automated immunofluorescence microscopy using glial fibrillary acidic protein, vimentin, and CD45 immunostaining, and DAPI counterstaining. The preliminary Kaplan-Maier survival analysis based on CTC positivity was performed in 39 patients with a follow-up longer than two years. Results: We analyzed the CTC presence in 100 GBM patient peripheral blood samples. The CTCs or cancer cell clusters were found in 35% of GBM patients. The Kaplan-Maier survival analysis did not show a correlation between CTC presence and survival. This phenomenon may be associated with the generally short survival of these patients, which is expected to increase with advances in oncology and palliative care and/or a possible suppression of tumor cell growth outside the CNS. Conclusions: We have observed the CTCs in the peripheral blood of GBM patients. The patient enrollment and clinical data recording are still ongoing.
Citation Format: Pavel Stejskal, Josef Srovnal, Alona Rehulkova, Ondrej Kalita, Marek Slachta, Marian Hajduch. Glioblastoma multiforme disseminates outside the central nervous system [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B026.
A passagem do tudo ao nada: Roberto Schwarz entre colapsos temporais e desafios de geração
Authors: Graziani Vitor Morais 
Published: November 2024

At 2012, when happened the publication of the book Martinha versus Lucrécia, from the literary critic Roberto Schwarz, a review of Milton Ohata about the material came for us an interesting expresion to summarize Schwarz's work: "estatic future". From this notion, the present article wants to investigate a certain fenomenology of time at Roberto Schwarz's work, having as capital point for the anylisis the period before and after 1964's coup d'etat, moment that can institute the estatic future. Looking for the moviments of Roberto's dialetic thinking around the years, we want to apoint the changes and obstacles of dialetic critics to the brazilian experience, from the national-developmentalista pact at today. So, if 1964 ends an historical moment by a colpase (a colapse that does not end at 1964), another time begins, and new answers are expected from the dialetic critic.
Abstract 4119116: Percutaneous Aspiration of Mitral Valve Endocarditis using the AngioVac Device
Authors: Cao Jenny Jia Ling , Rihal Charanjit , Motiei Arashk , Kietselaer Bastiaan 
Published: November 2024

Case Description:
A 68-year-old man with end-stage renal disease on dialysis, peripheral vascular disease with metatarsal amputations, atrial fibrillation and type 1 diabetes was admitted for foot osteomyelitis secondary to MSSA bacteremia.

Transesophageal echocardiogram revealed mobile mitral valve vegetations up to 1.8cm on the atrial aspect of the posterior mitral valve leaflet which prolapsed through the mitral valve during diastole. Ejection fraction was 60% and there was trivial-mild mitral regurgitation without valvular destruction or peri-annular extension into the mitral annulus. MRI brain showed bilateral cerebral and cerebellar hemispheric infarcts, consistent with acute embolic stroke.
He was at high risk for both recurrent embolism and operative mortality (STS risk score 51%) due to his comorbidities and risk of hemorrhagic conversion of stroke. After shared decision making, percutaneous aspiration of the mitral vegetation was performed with AngioVac (Fig). Cerebral embolism protection devices were deployed prior to AngioVac evacuation of the mass.
There was no residual mitral regurgitation and only a small vegetation strand remained (Fig). Surgical pathology confirmed MSSA endocarditis. Blood cultures remained negative, and the patient did not suffer from recurrent embolic events. The patient underwent revision metatarsal amputation and was discharged with a 6-week course of IV cefazolin.

Discussion:
Infective endocarditis with high embolic risk is life-threatening and challenging to treat in patients with high surgical risk. We illustrate a case of percutaneous vegetation aspiration using the AngioVac device in our patient who suffered from embolic strokes due to MSSA mitral valve endocarditis. Meta-analyses have shown clinically successful debulking in 90% of cases, with 82% of patients able to clear bacteremia with AngioVac. Although most commonly used in right-sided lesions, percutaneous debulking of left-sided endocarditis with AngioVac and cerebral protection can be considered as a treatment strategy in select patients with prohibitive surgical risk.
Abstract 4124313: An unusual case of pericardial mass
Authors: Gong Jingyi , Gumuser Esra , O'Kelly Anna , Chen Maria , Tower-rader Albree , Yeh Doreen , Vaughn Jeanne , Dagogo-jack Ibiayi , Neilan Tomas 
Published: November 2024

A 30-year-old male electrician presented with two days of fever and positional left shoulder pain and was found to have elevated inflammatory markers and a large pericardial effusion with echocardiographic evidence of tamponade for which he underwent pericardiocentesis. He was discharged on a course of anti-inflammatory therapy with presumed diagnosis of idiopathic pericarditis based on negative cytology. He returned 6 months later with several weeks of upper respiratory infection symptoms as well as new abdominal discomfort and emesis.
On presentation, his vital signs were notable for tachycardia to 113 and cardiac exam was notable for tachycardia, regular rhythm, no rubs or murmurs, nondisplaced precordial impulse, normal jugular venous pressure with Kussmaul sign, and pulsus paradoxus of 6. An electrocardiogram showed sinus tachycardia with diffuse ST segment changes (Figure A). His cardiac biomarkers were unremarkable (troponin 21). His labs revealed normocytic anemia with hemoglobin of 11 and erythrocyte sediment rate above assay. Echocardiogram demonstrated a circumferential complex pericardial effusion with echocardiographic evidence of early tamponade (Figure B, C). A pericardiocentesis was attempted with inability to advance wire within pericardial space. A malignancy workup was initiated. CT demonstrated multi-station thoracic and lower cervical lymphadenopathy, moderate left pleural effusion, and an intrapericardial mass with associated pericardial effusion (Figure D). Cardiac magnetic resonance imaging demonstrated a circumferential intrapericardial non-mobile mass measuring up to 22 mm in thickness posteriorly and the mass was isointense to myocardium indicating low-fat content (Figure E). A supraclavicular lymph node biopsy was obtained with immunohistochemical staining positive for WT1 and calretinin, consistent with metastatic epithelioid mesothelioma of pericardial versus pleural etiology (Figure F). A PET-CT subsequently showed a FDG-avid circumferential anterior pericardial mass and multiple pleural-based lesions concerning for metastatic mesothelioma. He was initiated on pemetrexed/carboplatin systemic chemotherapy. With systemic therapy, his disease has been stable for 6 months. Pericardial mesothelioma is a rare malignancy. This case underscores the diagnostic challenges associated with pericardial mesothelioma and the importance of cancer workup as part of the pericardial effusion workup.
Validation of Left Ventricular Filling Pressure Evaluation by Order of Tricuspid and Mitral Valve Opening in Patients With Atrial Fibrillation
Authors: Nishino Hisao , Murayama Michito , Iwano Hiroyuki , Kagiyama Nobuyuki , Nakamura Yutaka , Akama Yuka , Toki Misako , Takamatsu Sachiko , Okada Taiji , Chiba Yasuyuki , Nakabachi Masahiro , Yokoyama Shinobu , Goto Mana , Suzuki Yukino , Ishizaka Suguru , Motoi Ko , Tamaki Yoji , Aoyagi Hiroyuki , Nakamura Kosuke , Kaga Sanae , Watanabe Chiaki , Kamiya Kiwamu , Nagai Toshiyuki , Teshima Takanori , Anzai Toshihisa 
Published: November 2024

BACKGROUND:
Accurate assessment of left ventricular filling pressure in patients with atrial fibrillation or flutter (AF) remains difficult. A novel 2-dimensional scoring system, visually assessing time difference between mitral valve and tricuspid valve opening (VMT) score, based on temporal analysis of early diastolic valve opening, could be applied to these patients. We aimed to determine the usefulness of the VMT score in patients with AF.

METHODS:
We analyzed 119 consecutive patients with AF who underwent cardiac catheterization as a derivation cohort. The diagnostic performance of the VMT score was further evaluated in an external data set containing 189 patients with AF. Elevated left ventricular filling pressure was defined as a mean pulmonary arterial wedge pressure ≥15 mm Hg. The time sequence of atrioventricular valve opening was visually assessed and scored (0, tricuspid valve first; 1, simultaneous; 2, mitral valve first). When the inferior vena cava was dilated, 1 point was added, and the VMT score was finally graded as 0 to 3. Conventional Doppler parameters to estimate left ventricular filling pressure were also measured.

RESULTS:

Pulmonary arterial wedge pressure was elevated with an increase in the VMT score (0: 10±3, 1: 13±5, 2: 22±7, 3: 27±6 mm Hg;
P
<0.001), resulting in a significant rise in pulmonary arterial wedge pressure from VMT score 1 to 2. VMT≥2 predicted elevated pulmonary arterial wedge pressure with an accuracy of 87%, and the diagnostic accuracy of the VMT score was significantly higher than that of conventional Doppler parameters (
C
index, 0.88 versus 0.54–0.68;
P
<0.001). In addition, VMT ≥2 showed an incremental predictive value over plasma brain natriuretic peptide levels (
C
index, 0.79–0.93;
P
<0.001). In the external validation cohort, VMT≥2 demonstrated acceptable accuracy of 72%.

CONCLUSIONS:
VMT scoring was a useful echocardiographic marker of elevated left ventricular filling pressure and had an incremental benefit over practical biomarkers in patients with AF.