bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic chest radiographic evaluation of the effects of tiotropium/olodaterol combination therapy in chronic obstructive pulmonary disease: the EMBODY study protocol for an open-label, prospective, single-centre, non-controlled, comparative study
Authors: Ikari Jun , Katsumata Megumi , Urano Akira , Imamoto Takuro , Suzuki Yuri , Nishiyama Akira , Yokota Hajime , Ono Kojiro , Okamoto Kentaro , Abe Eriko , Kamata Tomoko , Fujii Shota , Okumura Kenichiro , Ota Joji , Suzuki Eiko , Kawata Naoko , Ozawa Yoshihito , Masuda Yoshitada , Matsushita Kazuyuki , Sakao Seiichiro , Uno Takashi , Tatsumi Koichiro , Suzuki Takuji 
Published: August 2024

IntroductionTo date, there is limited evidence on the effects of bronchodilators on respiratory dynamics in chronic obstructive pulmonary disease (COPD). Dynamic chest radiography (DCR) is a novel radiographic modality that provides real-time, objective and quantifiable kinetic data, including changes in the lung area (Rs), tracheal diameter, diaphragmatic kinetics and pulmonary ventilation during respiration, at a lower radiation dose than that used by fluoroscopic or CT imaging. However, the therapeutic effect of dual bronchodilators on respiratory kinetics, such as chest wall dynamics and respiratory muscle function, has not yet been prospectively evaluated using DCR.AimThis study aims to evaluate the effects of bronchodilator therapy on respiratory kinetics in patients with COPD using DCR.Methods and analysisThis is an open-label, prospective, single-centre, non-controlled, comparative study. A total of 35 patients with COPD, aged 40–85 years, with a forced expiratory volume in the first second of 30–80%, will be enrolled. After a 2–4 weeks washout period, patients will receive tiotropium/olodaterol therapy for 6 weeks. Treatment effects will be evaluated based on DCR findings, pulmonary function test results and patient-related outcomes obtained before and after treatment. The primary endpoint is the change in Rs after therapy. The secondary endpoints include differences in other DCR parameters (diaphragmatic kinetics, tracheal diameter change and maximum pixel value change rate), pulmonary function test results and patient-related outcomes between pre-therapy and post-therapy values. All adverse events will be reported.Ethics and disseminationEthical approval for this study was obtained from the Ethics Committee of Chiba University Hospital. The results of this trial will be published in a peer-reviewed journal.Trial registration numberjRCTs032210543.
Multiple metal exposures associate with higher amyotrophic lateral sclerosis risk and mortality independent of genetic risk and correlate to self-reported exposures: a case-control study
Authors: Jang Dae-Gyu , Dou John F , Koubek Emily J , Teener Samuel , Zhou Lili , Bakulski Kelly M , Mukherjee Bhramar , Batterman Stuart A , Feldman Eva L , Goutman Stephen A 
Published: August 2024

BackgroundThe pathogenesis of amyotrophic lateral sclerosis (ALS) involves both genetic and environmental factors. This study investigates associations between metal measures in plasma and urine, ALS risk and survival and exposure sources.MethodsParticipants with and without ALS from Michigan provided plasma and urine samples for metal measurement via inductively coupled plasma mass spectrometry. ORs and HRs for each metal were computed using risk and survival models. Environmental risk scores (ERS) were created to evaluate the association between exposure mixtures and ALS risk and survival and exposure source. ALS (ALS-PGS) and metal (metal-PGS) polygenic risk scores were constructed from an independent genome-wide association study and relevant literature-selected single-nucleotide polymorphisms.ResultsPlasma and urine samples from 454 ALS and 294 control participants were analysed. Elevated levels of individual metals, including copper, selenium and zinc, significantly associated with ALS risk and survival. ERS representing metal mixtures strongly associated with ALS risk (plasma, OR=2.95, CI=2.38–3.62, p<0.001; urine, OR=3.10, CI=2.43–3.97, p<0.001) and poorer ALS survival (plasma, HR=1.37, CI=1.20–1.58, p<0.001; urine, HR=1.44, CI=1.23–1.67, p<0.001). Addition of the ALS-PGS or metal-PGS did not alter the significance of metals with ALS risk and survival. Occupations with high potential of metal exposure associated with elevated ERS. Additionally, occupational and non-occupational metal exposures were associated with measured plasma and urine metals.ConclusionMetals in plasma and urine associated with increased ALS risk and reduced survival, independent of genetic risk, and correlated with occupational and non-occupational metal exposures. These data underscore the significance of metal exposure in ALS risk and progression.
Chair's Letter
Authors: Palamidessi Catuscia 
Published: August 2024

Dear SIGLOG members,
As I am writing this letter, LICS is starting in Tallinn, Estonia, colocated with ICALP 2024 and FSCD 2024. Many thanks to the Local Organizer Pawel Sobocinski, and to the Program Committee Chairs Ugo Dal Lago and Javier Esparza for all their work. Many thanks also to the invited speakers Martin Escardo and Alexandra Silva, as well as to the invited tutorialists Sam Buss and Alex Simpson.
A Genomics-Driven Artificial Intelligence–Based Model Classifies Breast Invasive Lobular Carcinoma and Discovers CDH1 Inactivating Mechanisms
Authors: Pareja Fresia , Dopeso Higinio , Wang Yi Kan , Gazzo Andrea M. , Brown David N. , Banerjee Monami , Selenica Pier , Bernhard Jan H. , Derakhshan Fatemeh , da Silva Edaise M. , Colon-Cartagena Lorraine , Basili Thais , Marra Antonio , Sue Jillian , Ye Qiqi , Da Cruz Paula Arnaud , Yeni Yildirim Selma , Pei Xin , Safonov Anton , Green Hunter , Gill Kaitlyn Y. , Zhu Yingjie , Lee Matthew C.H. , Godrich Ran A. , Casson Adam , Weigelt Britta , Riaz Nadeem , Wen Hannah Y. , Brogi Edi , Mandelker Diana L. , Hanna Matthew G. , Kunz Jeremy D. , Rothrock Brandon , Chandarlapaty Sarat , Kanan Christopher , Oakley Joe , Klimstra David S. , Fuchs Thomas J. , Reis-Filho Jorge S. 
Published: August 2024

Abstract
Artificial intelligence (AI) systems can improve cancer diagnosis, yet their development often relies on subjective histologic features as ground truth for training. Herein, we developed an AI model applied to histologic whole-slide images using CDH1 biallelic mutations, pathognomonic for invasive lobular carcinoma (ILC) in breast neoplasms, as ground truth. The model accurately predicted CDH1 biallelic mutations (accuracy = 0.95) and diagnosed ILC (accuracy = 0.96). A total of 74% of samples classified by the AI model as having CDH1 biallelic mutations but lacking these alterations displayed alternative CDH1 inactivating mechanisms, including a deleterious CDH1 fusion gene and noncoding CDH1 genetic alterations. Analysis of internal and external validation cohorts demonstrated 0.95 and 0.89 accuracy for ILC diagnosis, respectively. The latent features of the AI model correlated with human-explainable histopathologic features. Taken together, this study reports the construction of an AI algorithm trained using a genetic rather than histologic ground truth that can robustly classify ILCs and uncover CDH1 inactivating mechanisms, providing the basis for orthogonal ground truth utilization for development of diagnostic AI models applied to whole-slide image.
Significance: Genetic alterations linked to strong genotypic–phenotypic correlations can be utilized to develop AI systems applied to pathology that facilitate cancer diagnosis and biologic discoveries.
A Phase Ib/II Randomized Clinical Trial of Oleclumab with or without Durvalumab plus Chemotherapy in Patients with Metastatic Pancreatic Ductal Adenocarcinoma
Authors: Coveler Andrew L. , Reilley Matthew J. , Zalupski Mark , Macarulla Teresa , Fountzilas Christos , Ponz-Sarvisé Mariano , Nagrial Adnan , Uboha Nataliya V. , Frentzas Sophia , Overman Michael , Noonan Anne , Messersmith Wells A. , Pavlakis Nick , Mettu Niharika B. , Bisha Ina , Wang Ying , Smith Paul , Murtomaki Elina , Bielska Agata A. , Bragulat Veronique , Cooper Zachary A. , Kumar Rakesh , Spigel David R. 
Published: August 2024

Abstract

Purpose:
Pancreatic ductal adenocarcinoma upregulates CD73, potentially contributing to immune surveillance evasion. Combining oleclumab (CD73 inhibitor) and durvalumab with chemotherapy may identify an effective treatment option.

Patients and Methods:
We describe a multicenter phase Ib/II randomized clinical trial in patients with metastatic pancreatic ductal adenocarcinoma, untreated (cohort A) or previously received gemcitabine-based chemotherapy (cohort B; NCT03611556). During escalation, patients received oleclumab 1,500 or 3,000 mg, durvalumab 1,500 mg, and gemcitabine plus nab-paclitaxel (GnP; cohort A; n = 14) or modified FOLFOX (cohort B; n = 11). During expansion, cohort A patients (n = 170) were randomized to GnP (arm A1), oleclumab [recommended phase II dose (RP2D)] with GnP (arm A2), or oleclumab (RP2D) with durvalumab plus GnP (arm A3). Primary objectives were safety (escalation) and objective response rate (expansion). Secondary objectives included progression-free survival (PFS) and overall survival (OS).

Results:
During escalation, 1/11 patients from cohort B (oleclumab 3,000 mg) experienced two dose-limiting toxicities. Oleclumab’s RP2D was 3,000 mg. During expansion, grade ≥3 treatment-related adverse events occurred in 67.7% (42/62) of patients in A1, 73.7% (28/38) in A2, and 77.1% (54/70) in A3. The objective response rate was 29.0%, 21.1%, and 32.9% in A1, A2, and A3, respectively (A1 vs. A3; P = 0.650). PFS [HR = 0.72; 95% confidence interval (CI), 0.47, 1.11] and OS (HR = 0.75; 95% CI, 0.50–1.13) were similar for A3 versus A1. Patients with high CD73 expression had improved PFS and OS in A3 versus A1, although this should be interpreted with caution.

Conclusions:
Although the safety profile was acceptable, this study did not meet its primary efficacy endpoint.
A Rose by Any Other Name: Mapping Taxonomic and Thematic Naming Errors Poststroke
Authors: Riccardi Nicholas , Schwen Blackett Deena , Broadhead Abigail , den Ouden Dirk , Rorden Chris , Fridriksson Julius , Bonilha Leonardo , Desai Rutvik H. 
Published: August 2024

Abstract
Understanding the neurobiology of semantic knowledge is a major goal of cognitive neuroscience. Taxonomic and thematic semantic knowledge are represented differently within the brain's conceptual networks, but the specific neural mechanisms remain unclear. Some neurobiological models propose that the anterior temporal lobe is an important hub for taxonomic knowledge, whereas the TPJ is especially involved in the representation of thematic knowledge. However, recent studies have provided divergent evidence. In this context, we investigated the neural correlates of taxonomic and thematic confrontation naming errors in 79 people with aphasia. We used three complementary lesion-symptom mapping (LSM) methods to investigate how structure and function in both spared and impaired brain regions relate to taxonomic and thematic naming errors. Voxel-based LSM mapped brain damage, activation-based LSM mapped BOLD signal in surviving tissue, and network-based LSM mapped white matter subnetwork integrity to error type. Voxel- and network-based lesion symptom mapping provided converging evidence that damage/disruption of the left mid-to-anterior temporal lobe was associated with a greater proportion of thematic naming errors. Activation-based lesion symptom mapping revealed that higher BOLD signal in the left anterior temporal lobe during an in-house naming task was associated with a greater proportion of taxonomic errors on the Philadelphia Naming Test administered outside of the scanner. A lower BOLD signal in the bilateral angular gyrus, precuneus, and right inferior frontal cortex was associated with a greater proportion of taxonomic errors. These findings provide novel evidence that damage to the anterior temporal lobe is especially related to thematic naming errors.
Intrinsic Rewards for Exploration Without Harm From Observational Noise: A Simulation Study Based on the Free Energy Principle
Authors: Tinker Theodore Jerome , Doya Kenji , Tani Jun 
Published: August 2024

Abstract
In reinforcement learning (RL), artificial agents are trained to maximize numerical rewards by performing tasks. Exploration is essential in RL because agents must discover information before exploiting it. Two rewards encouraging efficient exploration are the entropy of action policy and curiosity for information gain. Entropy is well established in the literature, promoting randomized action selection. Curiosity is defined in a broad variety of ways in literature, promoting discovery of novel experiences. One example, prediction error curiosity, rewards agents for discovering observations they cannot accurately predict. However, such agents may be distracted by unpredictable observational noises known as curiosity traps. Based on the free energy principle (FEP), this letter proposes hidden state curiosity, which rewards agents by the KL divergence between the predictive prior and posterior probabilities of latent variables. We trained six types of agents to navigate mazes: baseline agents without rewards for entropy or curiosity and agents rewarded for entropy and/or either prediction error curiosity or hidden state curiosity. We find that entropy and curiosity result in efficient exploration, especially both employed together. Notably, agents with hidden state curiosity demonstrate resilience against curiosity traps, which hinder agents with prediction error curiosity. This suggests implementing the FEP that may enhance the robustness and generalization of RL models, potentially aligning the learning processes of artificial and biological agents.
Prognostic Impact of Neoadjuvant Chemotherapy in Localized or Locoregionally Advanced Gallbladder Cancer: A Population-Based and Propensity Score Matched SEER Analysis
Authors: Xiong Yi-chen , Yang Zi-yi , Gong Albie , Wu Zi-you , Liu Shi-lei , Zhu Yi-di , Song Xiao-ling , Chu Bing-feng , Wu Xiang-song , Gong Wei 
Published: August 2024

Background The effect of neoadjuvant chemotherapy (NACT) in gallbladder cancer (GBC) patients remains controversial. The aim of this study was to assess the impact of NACT on overall survival (OS) and cancer specific survival (CSS) in patients with localized or locoregionally advanced GBC, and to explore possible protective predictors for prognosis. Methods Data for patients with localized or locoregionally advanced GBC (i.e., categories cTx-cT4, cN0-2, and cM0) from 2004 to 2020 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Patients in the NACT and non-NACT groups were propensity score matched (PSM) 1:3, and the Kaplan-Meier method and log-rank test were performed to analyze the impact of NACT on OS and CSS. Univariable and multivariable Cox regression models were applied to identify the possible prognostic factors. Subgroup analysis was conducted to identify patients who would benefit from NACT. Results Of the 2676 cases included, 78 NACT and 234 non-NACT patients remained after PSM. In localized or locoregionally advanced GBC patients, the median OS of the NACT and non-NACT was 31 and 16 months (log-rank P < 0.01), and the median CSS of NACT and non-NACT was 32 and 17 months (log-rank P < 0.01), respectively. Longer median OS (31 vs 17 months, log-rank P < 0.01) and CSS (32 vs 20 months, log-rank P < 0.01) was associated with NACT compared with surgery alone. Multivariable Cox regression analysis showed that NACT, stage, and surgery type were prognostic factors for OS and CSS in GBC patients. Subgroup analysis revealed that the survival hazard ratios (HRs) of NACT vs non-NACT for localized or locoregionally advanced GBC patients were significant in most subgroups. Conclusions NACT may provide therapeutic benefits for localized or locoregionally advanced GBC patients, especially for those with advanced stage, node-positive, poorly differentiated or undifferentiated disease. NACT combined with radical surgery was associated with a survival advantage. Therefore, NACT combined with surgery may provide a better treatment option for resectable GBC patients.
The work Lifestyle-integrated Functional Exercise program for preventing functional decline in employees aged 55 years and older: development and initial evaluation
Authors: Ritter Yvonne , Pfister Diana , Steckhan Greta M. , Voelter-Mahlknecht Susanne , Weber Britta , Ellegast Rolf , Koch Christian , Bausch Frank , Gruber Markus , Schwenk Michael 
Published: August 2024

Abstract
Background
Despite the global increase in older employees, workplace physical activity interventions (WPAIs) for this target group have not yet been sufficiently developed. The major drawback of existing WPAIs is low adherence due to lack of time or limited motivation. A novel approach could be to integrate tailored neuromotor and strength exercises into everyday working tasks to prevent the functional decline of older employees at the workplace without needing much additional time for training. This approach was tested in the present study by evaluating the proof-of-concept of a novel WPAI based on the Lifestyle-integrated Functional Exercise (LiFE) program integrated into a working environment (wLiFE55 +).

Methods
The proof-of-concept of wLiFE55 + was quantified within a 4-week pre-post exercise intervention study by measuring (1) feasibility including adherence, activity frequency, adverse events and acceptance (integrability of wLiFE55 + activities, perceived improvement and safety, satisfaction, physical demand, personal trainer session, intervention content) and (2) pre-to-post changes in neuromotor function (12-Level Balance Scale, 12-LBS; Community Balance and Mobility Scale, CBM), strength (60sec Chair Stand Test), and PA (1-week activity monitoring). For statistical analysis, the median and interquartile range (IQR) were computed. For pre-to-post changes, Wilcoxon signed-rank tests with effect size (r) were also performed.

Results
Seventeen older employees (mean age 59 years, 8 female) were included of which fifteen completed the study. The intervention adherence was 100%, and the activity adherence was 58% (9 out of 12 maximum possible wLiFE55 + activities implemented). Depending on the specific activity, the frequency of practice ranged between 25–75% of the days of the intervention period, and single wLiFE55 + activities were practiced between one and three times per day. No adverse events occurred, and acceptance was high. Pre-to-post increases with medium effect sizes were found for neuromotor function (CBM, 12-LBS) and specific PA variables (total sedentary time, sedentary bouts > 30 min).

Conclusion
The results of the study highlight the feasibility of wLiFE55 + in a work setting with older employees. The pre-to-post increases observed in neuromotor measures and reductions in sedentary time suggest that wLiFE55 + may counteract the age-related functional decline in older employees and justifies future studies in this field. The next steps are program adjustments to boost exercise frequency and evaluating wLiFE55 + in a randomized controlled trial.
The implementation of online and offline hybrid weight management approach for pregnant women based on the Fogg behavior model in Hainan, China: a pilot randomized controlled trial
Authors: Wang Linjie , Zou Lanli , Yi Huanying , Li Tong , Zhou Rong , Yang Jing , Wang Jia , Zhang Caihong , Guo Honghua 
Published: August 2024

Abstract
Objective
This study aimed at evaluating the effects of online and offline hybrid weight management approach based on the Fogg behavior model on total gestational weight gain and perinatal outcomes.

Methods
Pregnant women in Hainan, the southernmost province of China, were recruited into a randomized controlled trial, which was designed to develop a WeChat platform for pregnancy weight management, and implement individualized and continuous pregnancy weight management services for pregnant women under the guidance of the Fogg behavior model. All pregnant women participating in the study were included in the full analysis set (FAS) for analysis. The pregnant women who completed the intervention and provided all outcome indicators were included in the per protocol set (PPS) for outcome evaluation.

Results
Fifty-eight pregnant women were included in FAS analysis, and 52 pregnant women were finally included in PPS analysis. There was no statistically significant difference (P > 0.05) between the two groups at baseline. The gestational weight gain of the intervention group was significantly lower than that of the control group (P < 0.05). In the control group, the rate of appropriate weight gain during pregnancy was 48.26%, the rate of appropriate weight gain during pregnancy was 93.30% in the intervention group, with a statistically significant difference (P < 0.05). In the delivery outcomes, the cesarean section rate in the intervention group was significantly lower than that in the control group, and the differences were statistically significant (P < 0.05). The incidence of gestational diabetes mellitus and gestational hypertension in the intervention group was lower than those in the control group, and the differences were statistically significant (P < 0.05). The neonatal weight and incidence of macrosomia of the intervention group were lower than that of the control group, and the difference was statistically significant (P < 0.05).

Conclusions
This study combined the individualized and continuous pregnancy weight management of the online WeChat platform and offline consultation based on the Fogg behavior model, showing great potential in improving maternal and infant outcomes.

Trial registration
The study was registered with www.chictr.org.cn/index.aspx, Chinese Clinical Trial Registry (ChiCTR2200066707, 2022–12-14, retrospectively registered).
Assessment of hepatitis c core antigen in epithelial salivary gland neoplasms (ex-vivo study)
Authors: Kotat Hadeel Ahmad , Draz Awatef Ibrahim , ElShafei Marwa Mokbel , Amer Hatem Wael 
Published: August 2024

Abstract
Background
Salivary gland neoplasms (SGNs) pose a challenge to both pathologists and clinicians. Despite research, the etiology of these neoplasms remains unclear. This study aimed to identify any potential association between the presence of hepatitis C virus (HCV) at the protein or gene level and epithelial salivary gland neoplasms.

Methods
Formalin-fixed paraffin-embedded (FFPE) blocks of epithelial salivary gland neoplasms were retrieved from the archives of the Oral and Maxillofacial Pathology Department, Faculty of Dentistry, Cairo University within the 5-year period from 2016 to 2020. Immunohistochemistry was used to assess HCV core antigen, while reverse transcription polymerase chain reaction was employed for the evaluation of HCV RNA.

Results
A total of 44 specimens were collected, 28 of which were benign neoplasms and 16 were malignant neoplasms. There was a statistically significant difference in HCV positivity between the two groups (P-value = 0.036). Benign tumors showed a statistically significant lower percentage of positive cases than malignant tumors. The localization of staining was also evaluated, revealing various patterns of HCV core antigen expression, including diffuse cytoplasmic, patchy cytoplasmic, nuclear, and a combination of nuclear and cytoplasmic expression. There was no statistically significant difference between the expression patterns in benign and malignant tumors (P-value = 0.616). Given that Pleomorphic Adenoma and Mucoepidermoid Carcinoma were the predominant tumor types in this study, four cases were selected for RNA detection. HCV RNA was detected in all cases using RT-PCR.

Conclusions
HCV core antigen is frequently detected in SGNs and is suggested to be a potential risk factor for the development of these neoplasms. Further studies are required to discover other biomarkers, their roles, and the pathways associated with HCV in SGNs.