bluuebunny/crossref_metadata_2025_split huggingface dataset:
The tumor immune microenvironment features and their prognostic value in rectal and sigmoid colon signet-ring cell carcinoma.
Authors: An Yang , Su Lan , Lin Guole , Chen Han , Liu Yuxin , Zhou Jiaolin 
Published: June 2024

3544 Background: Signet-ring cell carcinoma (SRCC) of the rectum and sigmoid colon is a rare and highly malignant challenge in clinical practice. Although high PD-1+CD8+ tumor-infiltrating lymphocyte (TIL) infiltration has been reported as a positive prognostic factor in gastric cancer, pancreatic cancer, etc., its role in colorectal SRCC remains unclear. This study aims to explore the immune landscape of colorectal SRCC and its prognostic implications. Methods: The study included 34 patients with stage II-IV SRCC of the rectum and sigmoid colon. The immune contextures of tumor tissues were characterized using multiplex immunofluorescence assays and compared with a cohort of 57 cases of stage II-IV AC. The ratio density and spatial distribution of CD3+, CD8+, PD-1+, PD-L1+ cells, M1/M2 macrophages, and NK cells were quantitively analyzed in both parenchymal (p) and interstitial (i) regions. Characteristics of immune cell infiltration and their prognostic value for long-term survival were investigated in SRCC cases. Results: Compared to AC, SRCC exhibited significantly higher infiltration of CD8+ and CD3+ iTILs in the interstitial region (P=0.00024; P=0.00321, respectively) and elevated CD8+ pTILs infiltration in tumor parenchyma (P=0.041). Conversely, parenchymal infiltration of TILs co-expressing PD-1 was significantly lower in SRCC than AC (PD-1+CD8+ pTILs: P=0.00035; PD-1+CD3+ pTILs: P=5.0e-05). SRCC showed significantly lower infiltration of M1 macrophages in both parenchyma and interstitium (P=0.0035; P=5.4e-09, respectively), lower interstitial infiltration of M2 macrophages (P=1.5e-05), and a borderline lower parenchymal infiltration of M2 macrophages (P=0.0522), compared to AC. Additionally, patients with high parenchymal or interstitial infiltration of PD-1+CD8+ TILs exhibited significantly longer DFS (P=0.00024; P=0.0041, respectively) and OS (P=0.011; P=0.0044, respectively) than those with low infiltration. Multivariate analysis indicated that the level of PD-1+CD8+ pTILs infiltration is an independent prognostic factor for DFS, being independent of CEA levels and TNM stage (P = 0.018; P = 0.02, respectively). Among patients with normal CEA level or of stage II-III, high level of PD-1+CD8+ pTILs infiltration was still associated with significantly improved DFS (P<0.0001; P=0.00018, respectively) and OS (P=0.00021; P<0.0001, respectively). Conclusions: SRCC of rectum and sigmoid colon exhibits distinct immune profiles compared to conventional AC, characterized by higher infiltration of CD8+ and CD3+ TILs, but lower infiltration of PD-1+CD8+ TILs. The unique immune landscape in SRCC, particularly the level of PD-1+CD8+ TILs infiltration and its positive predictive value for DFS and OS, provides new perspectives for immune-based stratification and therapeutic strategies for this clinically significant cancer subtype.
A phase 2 study evaluating response and biomarkers in patients with microsatellite stable (MSS) advanced colorectal cancer (CRC) treated with nivolumab/relatlimab.
Authors: Christenson Eric , Durham Jennifer N. , Brancati Madelena , Davis Bruning Heather , Petrie Susan , Wang Hao , Lu Jiayun , Bever Katherine M. , Laheru Dan , De Jesus-Acosta Ana , Donehower Ross C. , Pishvaian Michael J. , Azad Nilofer Saba , Zhu Qingfeng , Llosa Nicolas Jose , Housseau Franck , Anders Robert , Pardoll Drew M. , Le Dung T. 
Published: June 2024

3554 Background: Lymphocyte-activation gene 3 (LAG-3) is an immunosuppressive signal, impairing T effector (Teff) activation. Pre-clinical studies suggest LAG-3 inhibition promotes anti-tumor immunity by enhancing Teff function. Correlative studies linked increased LAG-3 levels with reduced overall survival (OS) in CRC. These data prompted optimism that combined LAG-3/PD-1 inhibition might promote anti-tumor responses in MSS CRC. Methods: We conducted a phase 2 study of nivolumab (Nivo) (aPD1)/relatlimab (Rela) (aLAG3) in patients with previously treated advanced MSS CRC. This study enrolled patients onto 1 of 3 arms. Arms A and B used a Composite PD-L1 and acellular Mucin (CPM) score to define patients as CPM(+) in Arm A (CPM≥ 15%) and CPM(-) in Arm B (CPM< 15%). Patients in Arm A and B received Nivo 480mg/Rela 160mg IV q4 weeks. Arm C enrolled patients without biomarker selection who received Nivo 480mg/Rela 960mg or Rela 480mg/Nivo 480mg. The primary endpoint was objective response, and each arm was powered to detect an objective response rate (ORR) of ≥20%. Results: Fifty nine evaluable patients were enrolled (Arm A: 12, Arm B: 15, Arm C: 32). Patient characteristics and responses are outlined. Treatment was well tolerated with no new safety signals over aPD1 alone. Three (5%) patients achieved a partial response (PR), 6 (10%) stable disease (SD), and 50 with progression of disease (PD) as best response. The median progression-free survival was (Arm A: 2.2 mo., Arm B: 2.8 mo., Arm C: 2.6 mo.) while median OS was (Arm A: 4.3 mo., Arm B: 14.2 mo., Arm C: 12.4 mo.). In N=6 patients with lung-only metastases, 2 (33%) experienced a PR, and 1 (17%) a SD, for a clinical benefit rate of 50%. The trial incorporated translational correlates. We will report mass cytometry on PBMCs, RNAseq on baseline biopsies, and imaging mass cytometry on pre- and on-treatment biopsies. Conclusions: This combination did not meet the primary endpoint of 20% ORR for any of the 3 cohorts, but there was intriguing possible activity in patients with lung only metastases, consistent with emerging data. Clinical trial information: NCT03642067 .
Safety in the use of granulocyte-colony stimulating factor during concurrent chemotherapy and thoracic radiotherapy in patients with small-cell lung cancer: A meta-analysis.
Authors: Zarpelão Fabíola Furtuoso , Barbosa Larissa Irigoyen Teixeira , Sousa Jhefferson da Silva , Napoleão Luísa , De Souza Abner Lucas , Vilbert Maysa 
Published: June 2024

e20124 Background: There is an ongoing debate about whether patients with small cell lung cancer (SCLC) undergoing concurrent chemoradiotherapy should receive granulocyte-colony stimulating factor (G-CSF). The main concern relies on safety issues. Therefore, we performed a systematic review and meta-analysis to assess the safety and efficacy of prophylactic G-CSF use in patients with SCLC receiving concurrent chemoradiotherapy. Methods: We systematically searched the MEDLINE, Cochrane, and EMBASE databases up to December 2023 for studies assessing prophylactic use of G-CSFs versus non-prophylactic use in SCLC undergoing concurrent chemoradiotherapy. We included randomized and non-randomized clinical trials. The main safety outcomes were thrombocytopenia, febrile neutropenia, anemia, and radiotherapy toxicity. We performed statistical analysis using RevMan 5.4.1 and pooled odds ratio (OR) and 95% confidence interval (95%CI) of binary outcomes. We defined a significant threshold as p-value < 0.05. We used I² statistics for heterogeneity, with I² > 25% being defined as high heterogeneity. Results: We included five studies with a total of 774 patients, of whom 322 (42%) received G-CSF prophylactically, and 452 (58%) were in the control group. The majority of patients (97.5%) presented with Limited Stage disease. The minimum follow-up period had a median duration of 16.9 months, while the maximum follow-up extended to a median of 45 months (Table). Patients in the prophylactic group had a significantly lower incidence of neutropenia (OR: 0.34; 95% CI: 0.14-0.85; p = 0.02) than those who did not use G-CSF prophylactically. Radiotherapy toxicity (OR: 0.98; 95% CI: 0.63-1.53; p = 0.93) and severe hematological toxicity (grade III-IV) were similar in both groups. Hematological toxicity included thrombocytopenia (OR: 1.21; 95% CI: 0.32-4.58; p = 0.78), febrile neutropenia (OR: 1.11; 95% CI: 0.29-4.28; p = 0.88), and anemia (OR: 0.51; 95% CI: 0.13-1.97; p = 0.33). Conclusions: Our systematic review and meta-analysis supports the prophylactic use of G-CSF during concurrent chemoradiotherapy for patients with SCLC. Prophylactic G-CSF promoted a significant reduction in the incidence of neutropenia without any hematologic or radiotherapy-related toxicity increase. Incorporating G-CSF prophylaxis into SCLC chemoradiotherapy regimens can be a beneficial strategy for minimizing neutropenic complications without compromising overall treatment safety. [Table: see text]
Phase II study of anlotinib plus durvalumab and chemotherapy as first-line treatment in extensive-stage small cell lung cancer (ES-SCLC): Efficacy and safety analysis.
Authors: Chen Lijuan , Zhao Yanqiu 
Published: June 2024

e20131 Background: The combination of PD-L1 Checkpoint inhibitor and chemotherapy has revolutionized the first-line standard of care of ES-SCLC, yet the prognosis still need to be improved. In this phase 2 study, we aimed to enhance the patients benefit by adding anlotinib to durvalumab and chemotherapy, assessing its efficacy and safety. Methods: Eligible treatment naïve ES-SCLC patients, aged 18-75 years, were enrolled. Anlotinib + durvalumab + etoposide + carboplatin or cisplatin was administered for 4-6 cycles, followed by anlotinib and durvalumab maintenance until disease progression or intolerable toxicity. During the treatment, dose reduction of anlotinib was permitted, which could be reduced to 10mg or 8mg if it was intolerable. The primary endpoint is overall objective response rate (ORR), secondary endpoints are PFS and safety. Results: Between December 2020 and June 2022, 22 patients with extensive-stage SCLC were enrolled, including 8 patients (36.4%) with brain metastases and 11 patients (50%) with liver metastases. The median age was (39-73) years, 15 patients were males (68.2%). ORR was 100%, with 27.3% complete response rate (CR). The median PFS of all patients was 8.51months, and the PFS of patients with liver metastasis and brain metastasis were 9.43 months and 8.51 months respectively. The median OS was not reached. The most common grade ≥3 TEAEs ( > 10% incidence) included neutropenia and leukopenia (each 16.7%, 2/22), no new safety signals were observed. No grade 5 AE occurred. Conclusions: Durvalumab plus anlotinib and chemotherapy demonstrated promising PFS, ORR and manageable safety profile for the first-line treatment of ES-SCLC. Clinical trial information: NCT04660097 .
Fast Exact Simulation of the First Passage of a Tempered Stable Subordinator Across a Non-Increasing Function
Authors: González Cázares Jorge Ignacio , Lin Feng , Mijatović Aleksandar 
Published: June 2024

We construct a fast exact algorithm for the simulation of the first-passage time, jointly with the undershoot and overshoot, of a tempered stable subordinator over an arbitrary, nonincreasing, absolutely continuous function. We prove that the running time of our algorithm has finite exponential moments and provide bounds on its expected running time, with explicit dependence on the characteristics of the process and the initial value of the function. The expected running time grows most cubically in the stability parameter (as it approaches either 0 or 1) and is linear in the tempering parameter and the initial value of the function. Numerical performance, based on the implementation in the dedicated GitHub repository, exhibits a good agreement with our theoretical bounds. We provide numerical examples to illustrate the performance of our algorithm in Monte Carlo estimation. Funding: J. I. González Cázares and A. Mijatović are supported by the EPSRC Grant EP/V009478/1 and by The Alan Turing Institute under the EPSRC grant EP/X03870X/1. A. Mijatović is also supported by the EPSRC grant EP/W006227/1. F. Lin is funded by The China Scholarship Council and The University of Warwick PhD scholarship.
CONDUTAS DO PROFESSOR PRECEPTOR NO PROGRAMA DE INICIAÇÃO À DOCÊNCIA, POSSÍVEIS INFLUÊNCIAS E IMPACTOS NA FUTURA ATUAÇÃO PROFISSIONAL DOS BOLSISTAS
Authors: SANTOS JASSILENE 
Published: June 2024

Este relato de experiência foi produzido por uma estudante bolsista, do curso de Licenciatura de Educação Física da Universidade Estadual de Feira de Santana (UEFS). O material foi elaborado durante a participação no Programa Residência Pedagógica, vinculado à Universidade, no edital 001/PRP/UEFS/2022, e deu enfoque às observações da bolsista a respeito do profissional professor preceptor, que acompanha os bolsistas do Programa na escola campo. Neste relato, estão elencadas considerações a respeito das singularidades dos trabalhos pedagógicos, a importância do professor preceptor, as experiências vivenciadas na escola campo sob a orientação desse profissional, e as apreensões e aprendizagens da bolsista residente, através da análise da conduta da professora preceptora que a acompanhou no Programa. Dentre as observações de relações possibilitadas no contexto do Programa, foi evidenciada a imprescindível conduta apropriada do professor preceptor atuante na escola campo, durante a vivência no Programa.
ORGANIZAÇÃO DO TRABALHO PEDAGÓGICO DO CONTEÚDO LUTAS NAS AULAS DE EDUCAÇÃO FÍSICA ESCOLAR PARA ALUNOS DO SEXTO ANO DO ENSINO FUNDAMENTAL: RELATO DE EXPERIÊNCIA
Authors: Menezes Campos Livia , De Jesus Thimoteo Vanessa Beatriz , Alves Nogueira Suzana , Silva Souza Willian 
Published: June 2024

O relato de experiência teve como objetivo apresentar os desafios e possibilidades que surgem ao organizar pedagogicamente o conteúdo de Lutas nas aulas de Educação Física Escolar, a partir das experiências vivenciadas nas aulas, em duas turmas de sexto ano do ensino fundamental, de uma escola da rede municipal de Feira de Santana, parceira do Programa Institucional de Bolsa de Iniciação à Docência (PIBID). Dessa forma, são relatadas as dificuldades enfrentadas e as estratégias utilizadas para superá-las, contribuindo no campo da docência para um olhar mais crítico por parte dos docentes diante da sua prática pedagógica e possibilitando que os estudantes tivessem um ensino com maior qualidade e de forma integral. Além disso, por meio deste trabalho, foi possível evidenciar a importância do PIBID durante a graduação em Licenciatura, uma vez que é uma oportunidade para os discentes colocarem seus conhecimentos adquiridos durante a formação em prática e conheçam a realidade da sala de aula, potencializando e desenvolvendo novas habilidades.
Influence of discontinuities on photonic waveguides
Authors: Bhatt Gaurang R. , Dave Utsav D. , Rocha-Rodrigues Janderson , Zadka Moshe , Datta Ipshita , Asenjo-Garcia Ana , Lipson Michal 
Published: June 2024

Fabrication-induced imperfections in photonic wire waveguides, such as
roughness, stitching errors, and discontinuities, degrade their
performance and thereby lower the yield of large-scale systems. This
degradation is primarily due to the high insertion losses induced by
imperfections, which scale nonlinearly with the index contrast in wire
waveguides. Here we investigate the influence of discontinuities in
photonic waveguides and later show a platform that is robust to
fabrication imperfections. Our platform is based on an array of
silicon nano-pillars, arranged to form a sub-wavelength (SW) grating
waveguide. We focus on investigating the robustness by considering an
abrupt break in the waveguide, as an extreme case of discontinuity. We
show that sub-wavelength silicon waveguides are robust against
unwanted large discontinuities relative to the operating wavelength.
We measure a transmission loss of <2.2 dB at 1550 nm, for a discontinuity of length 2.1 μm, when compared to more than 7 dB of loss in conventional silicon wire
waveguides for the same discontinuity. Our results show that this mode
of protection is broadband, covering the entire telecommunication band
(λ =1500–1600 nm). We believe that this
investigation of the influence of discontinuities in photonic
waveguides could be a step toward the realization of low-loss optical
waveguides.
A cross-sectional questionnaire study: Impaired awareness of hypoglycaemia remains prevalent in adults with type 1 diabetes and is associated with the risk of severe hypoglycaemia
Authors: Baxter Faye , Baillie Nicola , Dover Anna , Stimson Roland H. , Gibb Fraser , Forbes Shareen 
Published: June 2024

Objective
Impaired awareness of hypoglycaemia (IAH) is a risk factor for severe hypoglycaemia (SH) in type 1 diabetes (T1D). Much of the IAH prevalence data comes from older studies where participants did not have the benefit of the latest insulins and technologies. This study surveyed the prevalence of IAH and SH in a tertiary adult clinic population and investigated the associated factors.

Methods
Adults (≥18 years) attending a tertiary T1D clinic completed a questionnaire, including a Gold and Clarke score. Background information was collected from health records.

Results
189 people (56.1% female) with T1D (median [IQR] disease duration 19.3 [11.5, 29.1] years and age of 41.0 [29.0, 52.0] years) participated. 17.5% had IAH and 16.0% reported ≥1 episode of SH in the previous 12 months. Those with IAH were more likely to report SH (37.5% versus 11.7%, p = 0.001) a greater number of SH episodes per person (median [IQR] 0 [0,2] versus 0 [0,0] P<0.001) and be female (72.7% versus 52.6%, p = 0.036). Socio-economic deprivation was associated with IAH (p = 0.032) and SH (p = 0.005). Use of technology was the same between IAH vs aware groups, however, participants reporting SH were more likely to use multiple daily injections (p = 0.026). Higher detectable C-peptide concentrations were associated with a reduced risk of SH (p = 0.04).

Conclusion
Insulin pump and continuous glucose monitor use was comparable in IAH versus aware groups. Despite this, IAH remains a risk factor for SH and is prevalent in females and in older people. Socioeconomic deprivation was associated with IAH and SH, making this an important population to target for interventions.
Effectiveness of exercise intervention in relieving symptoms of ankylosing spondylitis: A network meta-analysis
Authors: Luo Yekui , Chen Yonghuan , Yan Xiangning , Zhang Lan , Shang Yuan , Seo Jae Chul 
Published: June 2024

Background
Ankylosing spondylitis(AS) is a chronic inflammatory rheumatic disease that leads to a reduced quality of life. Exercise appears to be one of the promising modes of intervention. The aim of this study was to review the available evidence and compare the effectiveness of different exercises in relieving symptoms of AS.

Methods
We searched the Pubmed, WOS, EMbase, CNKI, Cochrane Library, and Scopus databases. The search has spanned from the creation of the database until September 15, 2023. We extracted the first author, year of article publication, sample information, intervention, duration of intervention, and outcome indicators from the literature that met the inclusion criteria. The Cochrane Risk Assessment Tool was used to assess the risk of bias for included studies. I² was used to judge the consistency of the included studies. Egger’s test and Begg’s test were used to judge whether there was significant publication bias. Forest plots were used to compare intervention effects and SUCRA was provided to rank the effects of the interventions. This study has been registered in PROSPERO(No. CRD42024518522).

Results
After screening, 10 papers matched the inclusion criteria for this study, and the total sample size of the 10 papers was 623. Upon analysis, the papers included in this study did not have significant publication bias (Begg’s Test P = 0.210) and had good consistency (P>0.05). The direct comparisons showed that Running, Pilates, Stretching, Yoga, and Tai Chi were more effective interventions than traditional therapies. The effect sizes, confidence intervals, and number of studies for each intervention are shown below: Running [MD -1.90 (95% CI -3.14,-0.66) n = 1], Pilates [MD -1.70 (95% CI -2.90,-0.51) n = 1], Stretching [MD -1.54 (95% CI -2.21,-0.88) n = 4], Yoga [MD -1.24 (95% CI -2.18,-0.30) n = 1], Tai Chi [MD -0.78 (95% CI -1.44,-0.12) n = 2], Exergame[MD -0.80 (95% CI -1.99,0.39) n = 1], Swiss balls[MD -1.07 (95% CI -2.58,0.44) n = 1]. The indirect comparisons showed that the range of effect sizes for each sport intervention intersected the null line. Based on cumulative probability, the order of effectiveness of different exercises in relieving AS symptoms is Running, Pilates, Stretching, Yoga, Tai Chi, Exergame, and Swiss ball.

Conclusion
Running, Pilates, Stretching, Yoga, and Tai Chi provided significant relief from AS symptoms. Exergame and Swiss ball were not statistically significant in relieving AS symptoms. There were no significant differences in the effectiveness of different exercise interventions in relieving AS symptoms. Running may have the most beneficial effect on alleviating AS symptoms.
Patient experiences of hydrodistension as a treatment for frozen shoulder: A longitudinal qualitative study
Authors: Whelan Gareth , Yeowell Gillian , Littlewood Chris 
Published: June 2024

Background
Frozen shoulder is a condition associated with severe shoulder pain and loss of function impacting on a persons’ physical and mental health. Hydrodistension treatment that has been widely adopted within the UK National Health Service for the condition. However, evidence of clinical effectiveness and understanding of the patient experiences of this treatment are lacking. This study explored the experiences of people with a frozen shoulder who received hydrodistension treatment.

Methods
A qualitative design with repeat semi-structured interviews was used to explore participants’ experiences of hydrodistension treatment. Participants were interviewed 2–4 weeks and again at 8–10 weeks after treatment. Interviews were audio-recorded and transcribed verbatim. Findings were analysed using an inductive thematic analysis framework. The study is reported in accordance with the consolidated criteria for reporting qualitative (COREQ) research.

Results
15 participants were interviewed online or over the phone. Three themes were identified: ‘Preparing for and having a hydrodistension’, ‘Physiotherapy after hydrodistension’, and ‘Outcome of hydrodistension ‘. Participants believed hydrodistension would benefit them, was well tolerated by many, and the effects were apparent to most within the first week. Physiotherapy still seemed to be valued to support recovery beyond this timepoint, despite these early effects. Some participant’s experienced harms including severe procedural pain and blood sugar dysregulation.

Conclusion
This is the first study to investigate the experiences of people who undergo hydrodistension for frozen shoulder. Hydrodistension appears an acceptable treatment to participants with a frozen shoulder, acceptability is enhanced through adequate shared decision making. Further high-quality research is required to understand the comparative effectiveness of hydrodistension as a treatment for frozen shoulder, including adverse events, and the benefit of treatment by a physiotherapist after hydrodistension.