bluuebunny/crossref_metadata_2025 huggingface dataset:
Student evaluation of teaching (SET) in dental faculty: is it influenced by grouping the students according to their averages?
Authors: Sadrhaghighi Hooman , Zarghami Afsaneh , Irani Mahdi , Eskandarinezhad Mahsa , Sadrhaghighi Shahrzad , Parvaresh Mahdi
Published: January 2025

Purpose/objectives: Student evaluation of teaching (SET) is a crucial method for assessing teaching performance in higher education. This study aimed to evaluate the impact of grouping students by their academic averages on SET results in dental education.
Methods: In this descriptive-analytical study, 109 dental students were divided into five groups based on their academic averages: 48 in the top 30%, 15 in the top 10%, 17 in the middle 10%, 16 in the lower 10%, and 48 randomly selected from the bottom 30%. These groups completed questionnaires evaluating five university professors across four aspects: teaching methods, academic proficiency, communication and behavior, and organization and discipline in theoretical lessons. Two weeks later, internal reliability was assessed by redistributing the questionnaires to 10% of participants. Statistical analyses were performed using Chi-Square and ANOVA with SPSS 18, considering results significant at P < 0.05.
Results: The internal reliability of the statements was moderate. Significant differences in mean scores among rater groups were observed for teaching methods (P = 0.001), academic proficiency (P = 0.043), and communication and behavior (P = 0.012). However, no significant difference was found for organization and discipline (P = 0.855).
Conclusion: Grouping students according to their averages may influence SET in certain teaching aspects. However, this approach does not appear to affect professors' organization and discipline evaluation.
Relationship of Age and Running Biomechanics in Female Recreational Runners
Authors: Hamilton Heather M. , Bennett Hunter J. , Mariano Mira , Kakar Rumit Singh
Published: January 2025

Middle-age and older runners demonstrate differences in running biomechanics compared with younger runners. Female runners demonstrate differences in running biomechanics compared with males, and females experience hormonal changes during menopause that may also affect age-related changes in running biomechanics. The purpose of this study was to determine the relationship between age and running biomechanics in healthy female recreational runners. Fifty-two participants (ages 27–65 y) ran on an instrumented treadmill at 2 different self-selected speeds: easy pace and 5 km race pace. Lower-extremity kinematic and kinetic variables were calculated from 14 consecutive strides. Linear regression was used to determine the relationship between age and lower-extremity running biomechanics, controlling for self-selected running speed. There was a negative relationship between age and easy pace (R = −.49, P < .001) and age and 5 km race pace (R = −.43, P = .001). After controlling for self-selected running speed, there were no significant relationships between age and running biomechanics for either running speed. Several biomechanical variables were moderately to strongly correlated with running speed. Running speed should be considered when investigating age-related differences in running biomechanics.
Joint Associations of Sedentary Time and Intensity-Specific Physical Activity With Cancer Mortality: A Device-Based Cohort Study of 72,458 UK Adults
Authors: Rezende Leandro F.M. , Ahmadi Matthew , Ferrari Gerson , del Pozo Cruz Borja , Lee I-Min , Friedenreich Christine M. , Stamatakis Emmanuel
Published: January 2025

Background: There are no studies examining the prospective joint association of device-based measures of sedentary time and physical activity (PA) with cancer mortality. We examined the joint associations of sedentary time and intensity-specific PA with cancer mortality in 72,458 adults from UK Biobank. Methods: Participants wore an Axivity AX3 accelerometer on their dominant wrist for at least 3 days (with at least 1 weekend day). Cox regression was performed to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for joint associations of sedentary time and intensity-specific PA (light [LPA], moderate [MPA], and vigorous PA [VPA]) with cancer mortality (reference group: high intensity-specific PA and low sedentary time) adjusted for confounders and mutually adjusted for other PA intensities. Results: Associations between sedentary time and cancer mortality were stronger among participants with low PA, irrespective of the intensity. Compared with participants with lower sedentary time (<11 h/d) and high MPA (median of 49 min/d), HR were 1.27 (95% CI, 0.90–1.78) for high sedentary time and high MPA, 1.35 (95% CI, 1.03–1.77) for high sedentary time and medium MPA (49 min/d), and 1.49 (95% CI, 1.15–1.92) for high sedentary time and low MPA (13 min/d). HR for high sedentary time and low light PA (61 min/d) and high sedentary time and low vigorous PA (1 min/d) were 1.25 (95% CI, 1.02–1.59) and 1.57 (95% CI, 1.20–2.06), respectively. Conclusions: Relatively large amounts of LPA and MPA and small amounts of VPA appeared to attenuate the association between sedentary time and cancer mortality.
A Concussion Management Policy Change Promoted Earlier Initiation of Rehabilitation Services and Improved Clinical Recovery Outcomes in Concussion
Authors: Teel Elizabeth F. , Dobney Danielle , Friedman Deborah , Grilli Lisa , Beaulieu Christine , Gagnon Isabelle J.
Published: January 2025

Context: In line with emerging research, an interprofessional specialty concussion clinic instituted a policy change permitting earlier physiotherapy-based treatment entry. Our objective was to determine the effect of this policy change on concussion recovery outcomes. Design: Secondary analysis of prospectively collected clinical data. Methods: 600 youth with concussion were included. Active rehabilitation was initiated ≥4 weeks (prepolicy) or ≥2 weeks (postpolicy) postconcussion based on institutional policy. Cox proportional hazard models, linear mixed models, and chi-square analyses were conducted. Results: The postpolicy group (median = 22 d [interquartile range: 17–27]) started treatment earlier than the prepolicy group (median = 26 d [interquartile range: 24–30], P < .001). Length of episode of care (χ2(1) = 11.55, P < .001, odds ratios = 1.49; 95% confidence interval, 1.19–1.88); rehabilitation (χ2(1) = 9.47, P = .002, odds ratios = 1.73, 95% confidence interval, 1.22–2.45]); and total recovery (χ2(1) = 11.53, P < .001, odds ratios = 1.49; 95% confidence interval, 1.18–1.88) were reduced in patients postpolicy change. A significant interaction effect was found for total postinjury symptom (F2,320 = 3.59, P = .03) and symptom change scores (F2,315 = 5.17, P = .006), with the postpolicy group having faster symptom resolution over time. No group differences were observed for persisting symptoms. Conclusions: Earlier rehabilitation initiation occurred as intended following an institutional policy change, which had small, but significant, effects on recovery outcomes in youth with concussion. Health care providers should adopt policies to encourage early active rehabilitation services after concussion.
Loaded Open Kinetic Chain Exercises Caused More Anterior Tibial Translation and Anteromedial Graft Elongation Than Closed Kinetic Chain Following Double-Bundle Anterior Cruciate Ligament Reconstruction
Authors: Zhang Ling , Yang Yangyang , Xia Chunjie , Wang Cong , Qiu Jiayu , Chen Jiebo , Tsai Tsung-Yuan , Zhao Jinzhong , Wang Shaobai
Published: January 2025

Context: To further improve rehabilitation programs while preventing overstretching the anterior cruciate ligament (ACL), a thorough understanding of the knee kinematics and ACL length change during closed kinetic chain and open kinetic chain (OKC) exercises is essential. The measurement of ACL graft length relates to the changes in strain experienced by the ACL graft during different types of exercises rather than simple physical length. Objective: This study aimed to determine the effects of closed kinetic chain and OKC exercises on tibiofemoral kinematics and ACL graft length changes following double-bundle ACL reconstruction. Design: Cohort study (diagnosis); level of evidence, 3. Setting: Laboratory. Patients: Fifteen patients who underwent double-bundle ACL reconstruction were asked to perform 10-kg loaded seated knee extension (OKC-10) and single-leg lunge. During the seated knee extension, patients were instructed to extend and flex the knee within a range of 0° to 90° of flexion, with a 10-kg load applied to the ankle. For the lunge, patients began in a natural standing position and were instructed to flex the ACL-reconstructed knee to approximately 90°. Interventions: The 3-dimensional tibiofemoral kinematics under different weight-bearing conditions were determined using a dual-fluoroscopic imaging system. Main Outcome Measures: The tibiofemoral kinematics in 6 degrees-of-freedom were measured. And 3-dimensional ligament simulation technique was used to quantify length changes of the anteromedial bundle and posterolateral bundle. Results: The tibia exhibited significantly more external rotation during the OKC-10 motion than during the single-leg lunge from 35° to 70° of knee flexion (P ≤ .028). Beyond 30° of knee flexion, the tibia exhibited significantly more varus during the OKC-10 motion than during the single-leg lunge (P ≤ .028). And a significantly more anterior tibial translation was observed during the OKC-10 motion than during the lunge from 0° to 15° of flexion (P ≤ .018). The anteromedial bundle length was significantly longer during the OKC-10 motion than during the lunge between 0° and 25° of knee flexion (P ≤ .028). Conclusions: The effects of OKC exercises with loads on knee rotational stability should be considered in making rehabilitation programs for patients after ACL reconstruction. Since some degree of anterior tibial translation is physiological, it is important to note that increased translation alone does not necessarily indicate danger or instability.
A co-designed health education model to improve outcomes for children with emotional and behavioural difficulties: a study of acceptability, feasibility and impacts
Authors: Garvey William , Chen Lingling , Oberklaid Frank , Hiscock Harriet
Published: January 2025

Objective

To assess the acceptability and impacts of a co-designed health education model aiming to improve outcomes for children with emotional and behavioural difficulties.

Design

Qualitative focus group study.

Setting

Six primary schools from metropolitan and rural settings in the state of Victoria, Australia.

Participants

36 educators who engaged with the intervention between July and December 2021.

Intervention

Co-designed community of practice, led by a paediatrician, with fortnightly tailored case-based discussions aiming to build educator capacity to identify and support children with emotional and behavioural difficulties.

Main outcome measures

At the completion of the intervention, all educators were invited to participate in focus groups with their school group. The lead author facilitated the groups. Semistructured questions guided the sessions focusing on the motivation of participants, their experience of the intervention, its impact on their work and suggestions for possible improvements and impact upon their own well-being. Sessions were audio recorded, and field notes were taken by the facilitator. Interpretative phenomenological analysis was carried out to evaluate the data collected.

Results

36 of 46 educators completed six focus groups (one per school). Participants were highly motivated due to the mental health needs of their students. Participants experienced the intervention as stimulating and providing practical strategies. Participants discussed the positive impact it had on their capacity to support children with emotional and behavioural difficulties as well as their own well-being.

Conclusions

The intervention is highly acceptable to educators, and evaluating this intervention with a larger sample will inform expansion.
Patient and provider factors associated with follow-up for positive depression screens in adults: a retrospective review of University of Utah primary and specialty care clinics
Authors: Battiola Tess , Ellison Tanner , Dummer Danica , Weir Rachel , Kaput Katie , Reddy Deepika
Published: January 2025

Objective

To identify patient and provider factors associated with lower rates of follow-up for positive depression screens in outpatient settings.

Design

Retrospective cohort study with electronic health record analysis investigating factors associated with follow-up care for patients with moderate-to-severe depressive symptoms. Patient and provider variables were associated with rates of follow-up for positive depression screens.

Setting

University of Utah and University of Utah Health-affiliated primary care and specialty clinics.

Participants

Adults who screened positive for depressive symptoms (score≥10) on the Patient Health Questionnaire (PHQ-9) at an ambulatory visit between 1 January 2021 and 31 January 2022. A total of 17 651 patients were included in the study.

Outcome measures

Follow-up for positive depression screens was defined as a new antidepressant prescription or completed mental health visit. Variables associated with follow-up included patient demographic data, anthropometric measures, geographical classification, primary language, comorbidities and socioeconomic factors as well as provider demographics, level of training and clinic type.

Results

5396 patients (30.6%) did not receive follow-up care for a positive PHQ-9 screen. Factors associated with lower rates of follow-up included male patients (gender; p=0.013), older patients (age group; p=0.016), non-White patients (ethnicity; p<0.0001), non-English (primary language; p<0.0001), lack of insurance (p<0.0001), older providers (p=0.027), male providers (p=0.0037) and attending-level providers (p<0.0001).

Conclusions

Significant discrepancies in follow-up for positive depression screens in the ambulatory setting exist, particularly among racial/ethnic minority groups and patients who are non-native English speakers. Older providers and attending-level providers were less likely to facilitate follow-up for positive depression screens in their clinics.
Prevalence of visually significant cataract and cataract surgical coverage in Indigenous and non-Indigenous Australians: a systematic review and meta-analysis
Authors: Nejatian Marcel M , Bhat Saiuj , Kalantary Amy , Taylor Joshua R , Chia Mark A , Turner Angus W , Razavi Hessom
Published: January 2025

Aims

Compare the prevalence of age-related cataract and the cataract surgical coverage rate between Indigenous and non-Indigenous Australians and explore differences in these estimates across location and time.

Methods

The Joanna Briggs Institute guidance for systematic reviews of prevalence studies was followed. A systematic search of Medline, Embase, Web of Science and grey literature from database inception to June 2022 was performed. All studies reporting cataract prevalence in Australian populations were included. Pooled prevalence estimates were derived using meta-analyses with a random-effects model. Nine studies enrolling 36 302 participants were included. Most studies only reported the prevalence of cataract causing vision loss (visual acuity<6/12) or blindness (visual acuity<6/60), restricting our meta-analysis to these definitions.

Results

Cataract causing unilateral vision loss was common in both Indigenous and non-Indigenous adults (3.5% and 3.6%, p=0.891). Indigenous adults had a higher prevalence of bilateral vision loss (3.6% vs 1.1%, p=0.011) and bilateral blindness (0.385% vs 0.001%, p=0.002) than non-Indigenous adults. Cataract surgical coverage was lower in Indigenous (68.0%; 95% CI, 55.9 to 79.0) than non-Indigenous (88.4%; 95% CI, 79.9 to 94.8) adults (p=0.004). No differences in bilateral vision loss, blindness or surgical coverage were found between rural and urban subgroups or between studies conducted before and after the year 2000.

Conclusions

Cataract causes vision loss in a substantial number of adults living in urban and rural Australia. Policies to improve diagnosis and surgery rates should be prioritised, particularly for Indigenous Australians who experience a disproportionate burden of advanced cataract and reduced access to surgery.

PROSPERO registration number

CRD42022340197.
To be or not to be: a cross-sectional study on suicidal ideation, intensity of suicidal ideation and suicide attempts among medical students in Kerala, India
Authors: Varghese Sangeetha Merrin , Paulson Nikhil V , Ajayan Pranathi , Abraham Jithin Mathew , Thomas Pramod , Benjamin Anoop Ivan , Matteethra George Chandy
Published: January 2025

Background

India has one of the world’s largest medical consortiums. It has also shown an increasing trend in suicide rates among the medical fraternity in recent years. Recognising the bio-psychosocial context in which suicidal ideation and suicide attempts emerge are important steps in reducing the likelihood of suicide. However, the country lacks a comprehensive national programme to prevent suicidal deaths among medical students. It has become an important public health problem. This study aims to find the proportion of medical students with suicidal ideation and suicide attempts and to explore the factors associated with suicidal ideation in Kerala, India.

Methods

A cross-sectional study was conducted among undergraduate medical students from all 14 districts of the Kerala state of India. An online survey was conducted, and data was collected from government and private medical colleges across the state. A total of 1102 students participated in the survey, which used the Columbia Suicide Severity Rating Scale.

Results

The lifetime prevalence of suicidal ideation among medical students was 33.7% (30.88 to 36.54), and those with recent suicidal ideation were 15.2% (13.17 to 17.51). Those who had active suicidal ideation with specific plans were 5.4% (4.18 to 6.95), which puts them at 16 times higher risk of suicide when compared with their counterparts without suicidal ideation. Academic stress, parental pressure in deciding career choices, feelings of discrimination by peers and teachers, and family history of attempted suicide emerged as the key factors associated with suicidal ideation.

Conclusion

Suicidal ideation precedes suicide. Our research indicates that a significant portion, specifically one-third, of undergraduate medical students in Kerala are grappling with suicidal ideation. This situation calls for immediate, comprehensive interventions at a national scale aimed at tackling the myriad factors contributing to suicidal ideation among medical students.
Calcified chondroid mesenchymal neoplasm: a clinicopathological and molecular analysis
Authors: Feng Xiaolong , Wang Suxia , Wei Jiacong , Li Weihua , Wang Shun , Guo Peng , Guo Changyuan , Hao Weiwei , Dai Hongtian , Gong Lihua
Published: January 2025

Aims

Calcified chondroid mesenchymal neoplasm (CCMN) is a recently identified category of soft tissue neoplasms defined by cartilage or cartilaginous matrix formation andFN1gene fusions. Its rarity and similarities to other soft tissue tumours pose diagnostic challenges. This study aims to deepen understanding of CCMN, highlighting molecular pathology’s role in diagnosis to reduce misdiagnosis, overdiagnosis and overtreatment.

Methods

We conducted a clinicopathological analysis of five newly identified CCMN cases and reviewed 87 cases documented in PubMed. Next-generation sequencing was used to detect molecular alterations, while clinical, radiological and histopathological features were extensively reviewed.

Results

CCMN typically affects adults, presenting as a slow-growing, painless mass in soft tissue. Histologically, CCMN exhibits a chondroid matrix with variable calcification. Molecular analyses in our cases identifiedFN1::FGFR1,FN1::FGFR2andFN1::TEKfusions. Review of the 87 cases revealed consistent clinical, imaging and molecular profiles, underscoring CCMN’s distinct characteristics.

Conclusions

CCMN should be considered in the differential diagnosis of soft tissue tumours with chondroid and calcified components. DetectingFN1gene fusions aids in distinguishing CCMN from morphologically similar tumours.
Antibodies against the multifaceted cathepsin D protein open new avenues for TNBC immunotherapy
Authors: Desroys du Roure Pénélope , David Timothée , Mallavialle Aude , Laurent-Matha Valérie , Roger Pascal , Guiu Séverine , Chardès Thierry , Liaudet-Coopman Emmanuelle
Published: January 2025

Triple-negative breast cancer (TNBC) is a heterogeneous breast cancer subtype characterized by aggressive clinical behavior and poor prognosis. The immune landscape associated with TNBC often reveals high immunogenicity. Therefore, immunotherapy, which has demonstrated its efficacy in different cancer types, could be a promising strategy for TNBC, given the limited therapeutic options currently available besides conventional chemotherapy. The aspartic protease cathepsin D (cath-D) is a tumor cell-associated extracellular protein with protumor activity, a marker of poor prognosis, and a target for antibody-based therapy in TNBC. This commentary provides a synopsis/narrative summary of the development of anti-cath-D antibodies in different formats, their key roles in restoring the antitumor immunity, particularly via activation of tumor-infiltrating natural killer cells, and their dual antitumor effects on cancer cells and stromal cancer-associated fibroblasts, suggesting their interest for clinical use in the light of the current clinical knowledge on TNBC.
PD-1 suppresses human CD38+circulating Tfr cells and regulates humoral immunity
Authors: Zhang Heng , Zheng Hui , Wang Yanchun , Chen Cuncun , Tong Ying , Xie Suhong , Ma Xiaolu , Guo Lin , Lu Renquan
Published: January 2025

Background

Anti-programmed cell death protein 1 (anti-PD-1) antibodies have achieved revolutionary success in cancer therapy. However, the impact of anti-PD-1 therapy on host humoral immunity in humans during cancer immunotherapy requires further investigation.

Methods

We evaluated immunoglobulin titers by ELISA and screened the immune landscape of immune cells from 25 healthy donors and 50 cases including 25 new-onset hepatocellular carcinoma (HCC) patients prior to systemic treatment and 25 HCC patients undergoing anti-PD-1 therapy by multicolor flow cytometry. Flow or beads sorted cells were cultured ex vivo for proliferation and functional analysis.

Results

Anti-PD-1 therapy significantly increased the levels of IgG and IgA in the periphery of HCC patients. Anti-PD-1 treatment led to an increase in plasmablasts and a notable rise in circulating T follicular regulatory (cTfr) cells, while changes in circulating B cells, T follicular helper cells, or regulatory T cells were not significant. Anti-PD-1 therapy also influenced the proliferation and function of cTfr cells, promoting the differentiation of CD38+cTfr cells. We observed that the CD38+Tfr cell subset in the peripheral blood can promote plasmablast differentiation, associated with altered antibody production.

Conclusions

Together, these data demonstrate the immunomodulatory role of PD-1 in restricting the differentiation and function of human cTfr cells and in regulating humoral immunity.
Cancer vaccines compensate for the insufficient induction of protective tumor-specific immunity of CD3 bispecific antibody therapy
Authors: Middelburg Jim , Schaap Gaby , Sluijter Marjolein , Lloyd Katy , Ovcinnikovs Vitalijs , Schuurman Janine , van der Burg Sjoerd H , Kemper Kristel , van Hall Thorbald
Published: January 2025

Background

CD3 bispecific antibody (CD3 bsAb) therapy has become an established treatment modality for some cancer types and exploits endogenous T cells irrespective of their specificity. However, durable clinical responses are hampered by immune escape through loss of tumor target antigen expression. Induction of long-lasting tumor-specific immunity might therefore improve therapeutic efficacy, but has not been studied in detail yet for CD3 bsAbs. Here, we examined multiple combination strategies aiming to improve survival rates in solid tumors and, simultaneously, install endogenous immunity capable of protection to tumor rechallenge.

Methods

Two syngeneic mouse tumor models were employed: The immunologically “cold” B16F10 melanoma and the immunologically “hot” MC38.TRP1 colon carcinoma model. Mice were treated with CD3xTRP1 bsAb (murine Fc-inert immunoglobulin G2a) as monotherapy, or in combination with agonistic costimulatory antibodies, Fc-active tumor-opsonizing antibodies, or tumor-(non)specific vaccines. Treatment efficacy of primary tumors and protection from rechallenge was monitored, as well as induction of tumor-specific T-cell responses.

Results

In the immunologically “cold” B16F10 model, all combination therapies improved antitumor activity compared with CD3 bsAb monotherapy and induced systemic tumor-specific T-cell responses. However, this endogenous T-cell immunity swiftly waned and failed to protect mice from subsequent tumor rechallenge, except for combination therapy with tumor-specific vaccination. These vaccines strongly improved the therapeutic efficacy of CD3 bsAb against primary tumors and led to long-term immunological protection. In the immunologically “hot” MC38.TRP1 model, CD3 bsAb combined with only the vaccine adjuvant was sufficient to generate protective T-cell immunity and, moreover, prevented tumor escape via antigen loss.

Conclusions

These results demonstrate the impact of tumor antigenicity on the induction of protective endogenous antitumor immunity during CD3 bsAb treatment and, importantly, show that the combination with tumor-specific vaccines improves therapeutic efficacy and installs long-term immunological memory in both “hot” and “cold” tumors.
Early assessment of IL8 and PD1+ Treg predicts response and guides treatment monitoring in cemiplimab-treated cutaneous squamous cell carcinoma
Authors: Esposito Daniela , Napolitano Fabiana , Maresca Daniela Claudia , Scala Marcella , Amato Annarita , Belli Stefania , Ascione Claudia Maria , Vallefuoco Angela , Attanasio Giovanna , Somma Fabio , Ianaro Angela , Russo Daniela , Varricchio Silvia , Mascolo Massimo , Costa Claudia , Villani Alessia , Scalvenzi Massimiliano , Orlandino Gianfranco , Troiani Teresa , Servetto Alberto , Bianco Roberto , Ercolano Giuseppe , Formisano Luigi
Published: January 2025

Purpose

Anti-programmed cell death 1 (PD1) is the first-choice treatment in patients with advanced cutaneous squamous cell carcinoma (cSCC), when curative options are unavailable. However, reliable biomarkers for patient selection are still lacking.

Experimental design

In this translational study, clinical annotations, tissue and liquid biopsies were acquired to investigate the association between sustained objective responses and transcriptional profiles, immune cell dynamics in tumor tissue and peripheral blood samples, as well as circulating cytokine levels.

Results

First, we investigated the baseline characteristics of the immune landscape of cSCC biopsies. Gene Set Enrichment Analysis showed upregulation of interleukin (IL)2/STAT5 pathways and downregulation of Interferon signatures in non-responder patients compared with responders. Next, we studied the early changes induced by cemiplimab in tissue biopsies. Notably, after only three weeks, cemiplimab treatment induced an increase in B cells and CD8+ T cells in responders, whereas their abundance decreased in non-responder patients. Moreover, analyzing differentially expressed genes modulated early during treatment, compared with baseline biopsies, we found that IL1β and IL8 exhibited early downregulation in responder patients’ tumor specimens. We assessed whether changes in the local tumor microenvironment were mirrored in peripheral blood. Similar to tissue findings, no changes were observed in the whole T regulatory (Treg) population, although PD1+ Tregs, which were downregulated in responder patients (vs T0), showed a rebound enrichment in non-responders after three cycles of cemiplimab. Finally, IL8 mirrored the tissue results, unlike IL1β, with early (T1) and then sustained (T3) downregulation of its levels in responder patients, while increased in non-responders.

Conclusions

Taken together, these findings shed light on the significance of early transcriptomic and immune cell modulation in predicting responses to cemiplimab therapy. Additionally, our data suggest that IL8 levels in peripheral blood offer promising avenues for personalized treatment selection and response assessment in patients with cSCC receiving cemiplimab, while PD1+Tregs can be followed longitudinally to monitor response to therapy.
First-in-human phase I trial of the bispecific CD47 inhibitor and CD40 agonist Fc-fusion protein, SL-172154 in patients with platinum-resistant ovarian cancer
Authors: Lakhani Nehal J , Stewart Daphne , Richardson Debra L , Dockery Lauren E , Van Le Linda , Call Justin , Rangwala Fatima , Wang Guanfang , Ma Bo , Metenou Simon , Huguet Jade , Offman Elliot , Pandite Lini , Hamilton Erika
Published: January 2025

Background

SL-172154 is a hexameric fusion protein adjoining the extracellular domain of SIRPα to the extracellular domain of CD40L via an inert IgG4-derived Fc domain. In preclinical studies, a murine equivalent SIRPα-Fc-CD40L fusion protein provided superior antitumor immunity in comparison to CD47- and CD40-targeted antibodies. A first-in-human phase I trial of SL-172154 was conducted in patients with platinum-resistant ovarian cancer.

Methods

SL-172154 was administered intravenously at 0.1, 0.3, 1.0, 3.0, and 10.0 mg/kg. Dose escalation followed a modified toxicity probability interval-2 design. Objectives included evaluation of safety, dose-limiting toxicity, recommended phase II dose, pharmacokinetic (PK) and pharmacodynamic (PD) parameters, and antitumor activity.

Results

27 patients (median age 66 years (range, 33–85); median of 4 prior systemic therapies (range, 2–9)) with ovarian (70%), fallopian tube (15%), or primary peritoneal (15%) cancer received SL-172154. Treatment-emergent adverse events (TEAEs) were reported for 27 patients (100%), with 24 (88.9%) having a drug-related TEAE and infusion-related reactions being the most common. 12 patients (44.4%) had grade 3/4 TEAEs, and half of these patients (22.2%) had a drug-related grade 3/4 TEAE. There were no fatal adverse events, and no TEAEs led to drug discontinuation. SL-172154 Cmaxand area under the curve increased with dose with greater than proportional exposure noted at 3.0 and 10.0 mg/kg. CD47 and CD40 target engagement on CD4+T cells and B cells, respectively, approached 100% by 3.0 mg/kg. Dose-dependent responses in multiple cytokines (eg, interleukin 12 (IL-12), IP-10) approached a plateau at ≥3.0 mg/kg. Paired tumor biopsies demonstrated a shift in macrophages from an M2- to an M1-dominant phenotype and increased infiltration of CD8 T cells. PK/PD modeling showed near maximal margination of B cells and a dose-dependent production of IL-12 nearing a plateau at >3.0 mg/kg. The best response was stable disease in 6/27 (22%) patients.

Conclusions

SL-172154 was tolerable as monotherapy and induced, dose-dependent, and cyclical immune cell activation, increases in multiple serum cytokines, and trafficking of CD40-positive B cells and monocytes following each infusion. The safety, PK, and PD activity support 3.0 mg/kg as a safe and pharmacologically active dose.

Trial registration number

NCT04406623.
Depression and dementia: interrogating the causality of the relationship
Authors: Paris Alvar , Amirthalingam Guru , Karania Tasvee , Foote Isabelle F , Dobson Ruth , Noyce Alastair J , Marshall Charles R , Waters Sheena
Published: January 2025

Background

Depression is often cited as a major modifiable risk factor for dementia, though the relative contributions of a true causal relationship, reverse causality and confounding factors remain unclear. This study applied a subset of the Bradford Hill criteria for causation to depression and dementia including strength of effect, specificity, temporality, biological gradient and coherence.

Methods

A total of 491 557 participants in UK Biobank aged between 40 and 69 at enrolment and followed up for a mean duration of 12.4 years were studied. Diagnoses of depression and dementia were ascertained from linked health records, self-reports and death certificate registration. Depressive symptoms were measured at enrolment using a combination of questions based on the Patient Health Questionnaire-9 depression screening questionnaire. Regional grey matter volumes were measured using T1-weighted MRI in 41 929 participants.

Results

Depression was a strong risk factor for incident dementia with an OR of 1.76 (95% CI 1.63 to 1.90), a relationship which was found to be specific to depression rather than commonly proposed confounders. Depressive symptoms increased rapidly in the 10 years prior to dementia diagnosis. The severity of depressive symptoms showed a dose-response relationship with dementia risk. Depression at older ages correlated with reduced grey matter volume in an Alzheimer’s pattern whereas younger onset depression was associated with reduced grey matter volume in the frontal lobes and cerebellum.

Conclusions

This study provides evidence that the link between depression and dementia is due to reverse causation with a smaller component of causation with clear evidence of both mechanisms driving the association.
Whole body vibrations and lower back pain: a systematic review of the current literature
Authors: Bainbridge Abigail , Moutsos I , Johnson A , McMenemy L , Ramasamy A , Masouros S D
Published: January 2025

Introduction

Whole body vibration (WBV) is thought to be associated with low back pain (LBP). To mitigate against this the International Organisation for Standardisation (ISO) have created the ISO 2631 standard, recommending safe dose limits. The aim of this research is to conduct a systematic review of available literature addressing the question, is WBV associated with LBP?

Methods

A literature search was performed from January 1970 until April 2022, including studies focusing on LBP and sciatica in association with WBV, looking specifically for ones reporting on military populations. Studies on populations less than 18 years old or case studies were excluded. We conducted two subgroup analyses on studies that used a validated method to assess LBP and measured an A(8) (daily exposure) or VDV value (highest vibration exposure) as per ISO 2631-1 standard.

Results

37 studies were included, 11 showed an association between LBP and WBV. 97.9% of the population was male with an average age of 40.2, 47% used a version of the Standard Nordic Questionnaire (SNQ) to assess LBP and 51% used a triaxial accelerometer standard to measure vibration. Two studies reported on military populations.

The subgroup analysis for A(8) identified six studies with a total population of 1413. A(8) ranged from 0.17 m/s2to 0.59 m/s2and LBP prevalence from 25% to 66%. The subgroup analysis for VDV identified three papers with a total population of 1239. VDV ranged from 6.84 m/s0.75to 14.7 m/s0.75and LBP prevalence from 25% to 60.9%.

Discussion

This paper suggests WBV and LBP are associated but there is a research gap for high-level evidence and comparable data. The use of the SNQ was a preferrable method to assess LBP in most included studies. Using this in combination with a protocolised standard for measuring vibration exposure is needed for further research.

PROSPERO registration number

CRD42022298283.
Home-based self-collection of biological samples, including vaginal swabs: a mixed methods study for Britain’s fourth National Survey of Sexual Attitudes and Lifestyles (Natsal-4)
Authors: Oeser Clarissa , Sonnenberg Pam , Unemo Magnus , Sadler Katharine , Clifton Soazig , Gibbs Jo , Beddows Simon , Hamilton Rebecca , Roodt Abraham , Migchelsen Stephanie , Dema Emily , David Alexandra , Mercer Catherine H , Field Nigel
Published: January 2025

Objectives

The decennial National Surveys of Sexual Attitudes and Lifestyles (Natsal) provide general population prevalence estimates in Britain for key sexually transmitted infections (STIs) through biosampling. Since methodological choices can impact acceptability and response rates, we evaluated processes for Natsal-4, including face-to-face and remote interview arrangements, non-return of test results and vaginal swab collection in two pilot studies.

Methods

The pilots were conducted during June to August 2021 and February to March 2022. Participants aged 16–59 years were invited to provide urine samples (cisgender men and trans/gender diverse) or three vaginal swabs (cisgender women; urine was requested if vaginal swabs were declined) following interview. Samples were self-collected at home and posted to the laboratory by the interviewer if the interview was face to face, or by the participant if they preferred to collect the sample later or the interview was remote. Process feedback was collected after the first pilot via qualitative interviews with participants and after both pilots through informal interviewer debriefing.

Results

Of 261 participants interviewed (pilot 1=130; pilot 2=131), 161 (62%) consented to biosampling, of which 129 (49%) provided samples. A sample was received from 78/153 (51%) of women, of whom 60 (77%) provided vaginal swabs and 18 (23%) provided a urine sample. A urine sample was received from 51/108 (47%) cisgender men or trans/gender diverse participants. All samples collected immediately after face-to-face interviews were received (n=77), while 64% of samples from participants consenting to post samples after face-to-face interviews and 60% after remote interviews were received. Process feedback confirmed our methods were broadly acceptable.

Conclusions

We demonstrated that our approach to biosampling and STI testing for a national sexual health survey was reasonably acceptable and feasible in the period coming out the COVID-19 pandemic. Self-collection of vaginal swabs for research, which provide higher testing sensitivity than urine, was feasible and acceptable in a home setting.
Transcutaneous electrical acupoint stimulation for upper limb spasticity after stroke: effect and feasibility—a randomised pilot study
Authors: Wang Yuting , Zhang Lili , Yin Rui , Zhang Yuqing , Dai Zifeng , Wang Min , Song Jiali , Fan Xiaonong , Zhang Yanan , Yang Sha , Shen Yan , Yang Chen , Song Qian , Sun Sihan , Liu Jian
Published: January 2025

Importance

Limb spasticity is a common issue among stroke patients. Transcutaneous electrical acupoint stimulation (TEAS) is recommended as an alternative therapy for managing upper limb spasticity after stroke; however, its potential effects and feasibility remain uncertain.

Objective

To investigate the potential effects and feasibility of TEAS on motor function in patients with upper limb spasticity after stroke.

Methods

This randomised controlled, double-blined pilot study was conducted in two phases. All the patients were randomly divided into two groups: the TEAS group and the sham TEAS group. The intervention period for both TEAS and sham TEAS was 6 weeks, with each session lasting 30 min and conducted thrice weekly. The outcomes measured were the Fugl–Meyer Assessment–Upper Extremity (FMA-UE) score, the effective improvement rate, the modified Ashworth Scale (MAS), the Wolf Motor Function Test (WMFT), the visual analogue scale (VAS), the Barthel index (BI) and the surface electromyography (sEMG).

Results

All participants completed the course of therapy. Baseline characteristics were comparable across the two groups. Compared with the sham TEAS group, the TEAS group showed significant increases in FMA-UE score (P value=0.013), WMFT score (P value=0.001) and BI score (P value=0.008) at week 6. For integrated electromyogram (p=0.048) and root mean square of the biceps (p=0.033), lower scores were identified in the TEAS group compared with the sham TEAS group with a significant difference at week 6.

Conclusion

TEAS was acceptable and feasible in participants with upper limb spasticity after stroke. A pivotal study of this therapy is justified.
Nicotine levels in flavoured hookah (waterpipe) tobacco products: discrepancies between labelled and measured levels
Authors: Rezk-Hanna Mary , Ben Taleb Ziyad , Benowitz Neal L
Published: January 2025

Background

Hookah tobacco smoking is prevalent among youth and young adults. While health warning labels play a critical role in communicating the health risks of tobacco product use to consumers, compliance with US Federal Regulation’s nicotine warning requirements on hookah tobacco packaging is low. Some labelling suggests that consumers are exposed to ‘only 0.05% nicotine’. Here, this study sought to evaluate the accuracy of nicotine levels advertised on flavoured hookah tobacco packaging.

Methods

We measured nicotine content of commercial hookah tobacco in a total of 15 flavours purchased from five different manufactures, that were selected based on their popularity in the USA and UK markets. Concentrations of nicotine were determined by gas–liquid chromatography with nitrogen phosphorus detection, using 5-methyl nicotine as an internal standard. Nicotine content was expressed as a percentage of tobacco weight.

Results

Out of the 15 flavours tested and as compared with nicotine levels advertised on product packaging (0.05% nicotine), 12 (80%) had higher nicotine levels. Of these 12 flavours, actual nicotine levels ranged between 20% and 160% higher (0.08±0.01% vs 0.05%; mean±SE) than advertised levels. Estimates of determined levels of nicotine ranged from 0.05% to 0.13%.

Conclusion

Nicotine levels cited by leading hookah tobacco manufacturers are misleading. The advertised levels of nicotine do not reflect the quantified dose of nicotine available to consumers of hookah tobacco products. Findings highlight the need for the development of hookah tobacco product regulations and labelling standards, similar to other tobacco products, to avoid misleading vulnerable consumers, including youth and young adults.
Changes in multidisciplinary perceptions of trauma video review following implementation of a novel program: let us go to the tape
Authors: Murray Matthew , Rogers Eli , Dellonte Kate , Dumas Ryan Peter , Vella Michael A
Published: January 2025

Background

Trauma video review (TVR) is an evolving technology that can be used to measure technical and non-technical aspects of trauma care leading to meaningful improvements. Only 30% of centers currently use TVR, with non-users citing medicolegal concerns, staff discomfort with recording, and resource constraints as barriers to implementation. Multiple studies have shown established TVR programs are well-perceived by staff. Little is known about perceptions prior to, and after implementation of a new program.

Objective

This study evaluated changes in TVR perceptions following implementation of a new program.

Methods

A 15-question survey was distributed to emergency department and trauma surgery providers at a level I trauma center prior to, and 1 year after, implementation of TVR. A 5-point Likert scale was used to evaluate perceptions of the value of TVR, measures of team dynamics, and staff discomfort with recording.

Results

A total of 106 pre-implementation and 82 post-implementation responses were recorded. Perceptions in several domains improved post-implementation including team leader effectiveness (3 (3–4) to 4 (3–4); p=0.002), communication (3 (3–4) to 4 (3–4); p<0.001), and self confidence in role (4 (3–4) to 4 (4–5); p=0.001). Staff discomfort with recording decreased post-implementation (3 (2–4) to 2 (2–3); p=0.002).

Conclusion

Our study shows that perceptions of TVR changed favorably after implementation, particularly perceptions of team dynamics and provider discomfort with recording. These results can be used to mitigate staff concerns about TVR and encourage the development of new programs.

Level of evidence

IV.
Understanding the Modern Internet's Heterogeneous Congestion Control Landscape
Authors: Mishra Ayush
Published: January 2025

Research in Internet congestion control has experienced a renaissance in recent years, driven by two key developments. In 2016, Google introduced and deployed BBR, a congestion control algorithm that marks a significant departure from traditional loss-based algorithms like CUBIC and New Reno. Additionally, Internet transport is transitioning to the userspace with the adoption of QUIC, a new transport stack that is already widely deployed and poised to become the default with HTTP3. While both these advancements present unique challenges, they also introduce considerable heterogeneity into the Internet's congestion control landscape. Historically, Internet congestion control has remained stable due to a homogeneous ecosystem of well-understood AIMD congestion control algorithms. However, the recent innovations in BBR and QUIC are set to challenge this paradigm. This extended abstract summarises the contributions of my thesis, which examines the impact of these two developments on the Internet's congestion control landscape and explores how they are likely to influence its evolution in the near future.
Analysis of the Transaction Confirmation Process and Fairness in Proof-of-Work Blockchains
Authors: Malakhov Ivan
Published: January 2025

In recent years, blockchain technology has emerged as a pivotal tool for implementing distributed ledgers. This thesis provides an in-depth exploration of blockchains that rely on one of the most widely adopted consensus mechanisms: Proof-of-Work (PoW). In PoW-based systems, a fundamental tension exists between the operating costs borne by users - such as transaction fees - and the quality of service they receive, measured by transaction confirmation time and the likelihood of confirmation success.
Exploration, Collaboration, and Applications in Multi-Agent Reinforcement Learning
Authors: Chen Jingdi
Published: January 2025

Research Summary: In recent years, the field of humancentric decision-making has emerged as a critical area of research, driven by its potential to fundamentally reshape how decisions are made across a variety of complex systems. Human-centric decision-making is characterized by considerable variability, which can be both advantageous and problematic. Variability is beneficial in contexts like brainstorming or problem-solving, where diverse perspectives lead to innovation. However, in situations where consistency is crucial- such as public health, safety, and fairness-this variability can have negative consequences. For instance, when radiologists interpret the same mammogram differently, it can result in unnecessary medical procedures. Similarly, in military operations, inconsistent judgments by sonar technicians regarding potential threats can jeopardize both crew safety and mission success. This highlights the critical need for a deeper understanding of decisions where the stakes are high. Thus, it is important to deepen our understanding of the decision-making process in completed and dynamic scenarios that involve multiple decisionmakers. This should guide the creation of validated methods to identify, measure, model, and adjust variability in judgments to improve decision-making in multi-agent environments.
Game Theoretic Frameworks for Spectrum Coexistence in Advanced Wireless Networks
Authors: Chamberlain Jonathan
Published: January 2025

The research can be summarized into two broad areas, with overlap due to proliferation of edge compute clusters in 5G networks: a) flexible resource allocations in cloud environments and b) interactions between user agents in wireless spectrum allocations.