bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

ObjectiveTo identify patient and provider factors associated with lower rates of follow-up for positive depression screens in outpatient settings.DesignRetrospective 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.SettingUniversity of Utah and University of Utah Health-affiliated primary care and specialty clinics.ParticipantsAdults 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 measuresFollow-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.Results5396 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).ConclusionsSignificant 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

AimsCompare 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.MethodsThe 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.ResultsCataract 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.ConclusionsCataract 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 numberCRD42022340197.
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

BackgroundIndia 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.MethodsA 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.ResultsThe 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.ConclusionSuicidal 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

AimsCalcified 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.MethodsWe 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.ResultsCCMN 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.ConclusionsCCMN 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.
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

BackgroundAnti-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.MethodsWe 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.ResultsAnti-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.ConclusionsTogether, 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

BackgroundCD3 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.MethodsTwo 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.ResultsIn 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.ConclusionsThese 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

PurposeAnti-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 designIn 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.ResultsFirst, 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.ConclusionsTaken 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

BackgroundSL-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.MethodsSL-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.Results27 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.ConclusionsSL-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 numberNCT04406623.
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

BackgroundDepression 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.MethodsA 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.ResultsDepression 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.ConclusionsThis 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

IntroductionWhole 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?MethodsA 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.Results37 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%.DiscussionThis 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 numberCRD42022298283.