bluuebunny/crossref_metadata_2025_split huggingface dataset:
P27.17.B PRIMARY CNS LYMPHOMA IN YOUNGER PATIENTS: ANALYSIS OF A MONOCENTRIC COHORT RECEIVING THE MODIFIED BONN PROTOCOL AS PRIMARY THERAPY
Authors: Zeyen T , Weller J , Schneider M , Potthoff A , Schaub C , Röver L , Herrlinger U , Schäfer N 
Published: October 2024

Abstract

BACKGROUND
Polychemotherapy based on high-dose methotrexate (HD-MTX) is generally regarded ad standard therapy for newly diagnosed, younger patients with primary CNS lymphoma (PCNSL). Combination partners for HD-MTX vary between protocols (rituximab, ifosfamid (IFO), cytarabine (AraC), thiotepa (TT)). The type of consolidation therapy is even more variable (whole brain radiotherapy, high-dose therapy with stem cell rescue (HD-ASCT), continuation of standard-dose chemotherapy +/- intrathecal therapy). Successfull protocols are associated with a long-term survival (&gt;5years) rate of substantially more than 50%. We here report the retrospective analysis of our monocentric cohort treated with the modified Bonn protocol.

MATERIAL AND METHODS
All consecutive patients aged &lt;65 years who were newly diagnosed with PCNSL between 2012-2021 and recieved at least 1 cycle of the modified Bonn protocol as first-line therapy were included in this retrospective analysis. The modified Bonn protocol comprised 3 courses of rituximab/HD-MTX/IFO, implantation of an intraventricular catheter followed by consolidation therapy with 2 courses of HD-AraC and 2 courses of HD-MTX/IFO including intrathecal MTX and AraC in each course. Progression-free survival and overall survival were evaluated.

RESULTS
Forty patients with a median age of 58 years (range 38-64) and a median KPS of 80% (range 30-100) were included. Twenty-three patients (57.5%) had multiple cerebral lesions. Thirty-eight patients (95%) reached intrathecal consolidation therapy and 36 (90%) completed all seven courses of therapy. Grade 3/4 toxicity (CTCAE v5) was observed in 21 patients (52.5%); among those, nine had an infection grade 3/4 (22.5%). After a median follow-up (mFU) of 54.7 months (IQR 25-99.5 months), the median progression-free survival was 102.8 months (95%CI 0-211.5) and the 2-year progression-free survival rate was 55%. The 5-year overall survival rate was 80% (median not reached). Sixteen patients developing refractory/relapsed PCNSL received second line therapy using the modified Freiburg protocol (AraC/TT +/- HD-MTX/rituximab followed by HD-ASCT). A second relapse has been observed in 6 of these 16 patients so far (mFU 48.7 months).

CONCLUSION
First line treatment of PCNSL with the modified Bonn protocol is highly effective. Overall survival rates compare well with other seemingly more toxic PCNSL protocols in younger patients. In patients with relapsed/refractory disease, second line therapy according to the modified Freiburg protocol appears to be affective.
Increased access to pediatric specialist healthcare using eConsult: A retrospective observational cohort and case–control study
Authors: Lai Lillian , Roubos Sophia , Radhakrishnan Dhenuka , Benchimol Eric I , Wang Xuesong , Matai Lavina , Keely Erin , Liddy Clare , Murto Kimmo 
Published: October 2024

ABSTRACT

Objectives
Primary care practitioners (PCPs) report that using the Champlain BASE™ eConsult service (eConsult) averts one-third of face-to-face (FTF) specialist referrals, however, there are concerns about duplication of services and adverse patient outcomes. Following an eConsult, we evaluated patient healthcare utilization and associated treatment costs.

Methods
Retrospective cohort study (2014 to 2018) of patients (&lt;18 years old) for whom an eConsult visit averted a FTF specialist referral. Patients were linked to provincial health administrative databases and hospital electronic medical records for healthcare use for the same diagnosis and specialty for the 18 months following the eConsult. Concurrently, a retrospective case–control study compared utilization and costs between an eConsult versus a matched FTF visit for the same diagnosis. We also assessed PCP satisfaction.

Results
In follow-up, &lt;5% of the study cohort of eConsult patients (n = 242) later accessed the healthcare system for the identical diagnosis and specialty type. FTF visits generate more frequent outpatient visits (12.6 times more [95% CI: 2.28 to 69.66, P = 0.002]) and higher costs compared to eConsult visits. There were no hospital admissions or deaths in patients with eConsult. PCPs (98%) described eConsult as an excellent service.

Conclusions
Using eConsult is associated with &lt;5% of patients subsequently having a FTF visit for the same reason. Matched FTF visits generated more healthcare utilization and higher costs compared with eConsult. eConsult in pediatrics is safe and can minimize FTF specialist visits in elective cases and increase capacity, towards a more efficient and cost-effective healthcare system.
Curvature-directed anchoring and defect structure of colloidal smectic liquid crystals in confinement
Authors: Jull Ethan I L , Campos-Villalobos Gerardo , Tang Qianjing , Dijkstra Marjolein , Tran Lisa 
Published: October 2024

Abstract
Rod-like objects at high packing fractions can exhibit liquid crystalline ordering. By controlling how the rods align near a boundary, i.e. the anchoring, the defects of a liquid crystal can be selected and tuned. For smectic phases, the rods break rotational and translational symmetry by forming lamellae. Smectic defects thereby include both discontinuities in the rod orientational order (disclinations), as well as in the positional order (dislocations). In this work, we use experiments and simulations to uncover the geometrical conditions necessary for a boundary to set the anchoring of a confined, particle-resolved, smectic liquid crystal. We confine a colloidal smectic within elliptical wells of varying size and shape for a smooth variation of the boundary curvature. We find that the anchoring depends upon the local boundary curvature, with an anchoring transition observed at a critical radius of curvature approximately twice the rod length. Surprisingly, the critical radius of curvature for an anchoring transition holds across a wide range of rod lengths and packing fractions. The anchoring controls the defect structure. By analyzing topological charges and networks composed of maximum density (rod centers) and minimum density (rod ends), we quantify disclinations and dislocations formed with varying confinement geometry. Circular confinements, characterized by planar anchoring, promote disclinations, whereas elliptical confinements, featuring antipodal regions of homeotropic anchoring, promote long-range smectic order and dislocations. Our findings demonstrate how geometrical constraints can control the anchoring and defect structures of liquid crystals—a principle that is applicable from molecular to colloidal length scales.
Diverse social media experiences and adolescents’ depressive symptoms: the moderating role of neurobiological responsivity to rejected peers
Authors: Trekels Jolien , Maza Maria T , Capella Jimmy , Jorgensen Nathan A , Kwon Seh-Joo , Lindquist Kristen A , Prinstein Mitchell J , Telzer Eva H 
Published: October 2024

Abstract
Adolescents’ experiences with social media are complex and can impact their mental well-being differently. Our study aimed to understand how neurobiological sensitivities may moderate the association between different social media experiences and depressive symptoms. In a multiwave study, 80 adolescents (Mage = 13.06, SD = 0.58) took part in an functional magnetic resonance imaging task designed to gauge the neural responses when viewing accepted and rejected peers within their own social networks (Wave 1). We also collected self-reported measures of positive (digital social connection) and negative (digital pressure) experiences on social media and depressive symptoms (Waves 2 and 3). Our findings revealed that there were no significant associations between digital social connection, digital pressure, and depressive symptoms 1 year later. However, the association between digital social connection and depressive symptoms was moderated by neural responsivity. Specifically, for adolescents with reduced sensitivity to their rejected peers in the ventral striatum, right temporoparietal junction, and ventromedial prefrontal cortex, digital social connection was associated with reduced depressive symptoms 1 year later. These results emphasize the importance of individual differences in how adolescents’ brains respond to rejected peers in shaping the impact of online experiences on their mental well-being.
Group empathy for pain is stronger than individual empathy for pain in the auditory modality
Authors: Shao Min , Qiu Yulan , Zhang Yudie , Qian Huiling , Wei Zilong , Hong Mingyu , Liu Shuqin , Meng Jing 
Published: October 2024

Abstract
Humans live in collective groups and are highly sensitive to perceived emotions of a group, including the pain of a group. However, previous research on empathy for pain mainly focused on the suffering of a single individual (“individual empathy for pain”), with limited understanding of empathy for pain to a group (“group empathy for pain”). Thus, the present study aimed to investigate the cognitive neural mechanisms of group empathy for pain in the auditory modality. The study produced group painful voices to simulate the painful voices made by a group, and recruited 34 participants to explore differences between their responses to group painful voices and individual painful voices using the event-related potential (ERP) techniques. The results revealed that group painful voices were rated with higher pain intensity, more negative affective valence, and larger P2 amplitudes than individual painful voices. Furthermore, trait affective empathy scores of the participants were positively correlated with their P2 amplitudes of group painful voices. The results suggested that the group empathy for pain may facilitate affective empathetic processing in auditory modality.
Association of mechanical power and postoperative pulmonary complications among young children undergoing video-assisted thoracic surgery
Authors: Zhu Change , Zhang Rufang , Li Jia , Ren Lulu , Gu Zhiqing , Wei Rong , Zhang Mazhong 
Published: October 2024

BACKGROUND
Previous studies have discussed the correlation between mechanical power (MP) and lung injury. However, evidence regarding the relationship between MP and postoperative pulmonary complications (PPCs) in children remains limited, specifically during one-lung ventilation (OLV).

OBJECTIVES
Propensity score matching was employed to generate low MP and high MP groups to verify the relationship between MP and PPCs. Multivariable logistic regression was performed to identify risk factors of PPCs in young children undergoing video-assisted thoracic surgery (VATS).

DESIGN
A retrospective study.

SETTING
Single-site tertiary children's hospital.

PATIENTS
Children aged ≤2 years who underwent VATS between January 2018 and February 2023.

INTERVENTIONS
None.

MAIN OUTCOME MEASURES
The incidence of PPCs.

RESULTS
Overall, 581 (median age, 6 months [interquartile range: 5–9.24 months]) children were enrolled. The median [interquartile range] MP during OLV were 2.17 [1.84 to 2.64) J min−1. One hundred and nine (18.76%) children developed PPCs. MP decreased modestly during the study period (2.63 to 1.99 J min−1; P < 0.0001). In the propensity score matched cohort for MP (221 matched pairs), MP (median MP 2.63 vs. 1.84 J min−1) was not associated with a reduction in PPCs (adjusted odds ratio, 1.43; 95% CI, 0.87 to 2.37; P = 0.16). In the propensity score matched cohort for dynamic components of MP (139 matched pairs), dynamic components (mean 2.848 vs. 4.162 J min−1) was not associated with a reduction in PPCs (adjusted odds ratio, 1.62; 95% CI, 0.85 to 3.10; P
= 0.15).
The multiple logistic analysis revealed PPCs within 7 days of surgery were associated with male gender, OLV duration >90 min, less surgeon's experience and lower positive end-expiratory pressure (PEEP) value.

CONCLUSIONS
MP and dynamic components were not associated with PPCs in young children undergoing VATS, whereas PPCs were associated with male gender, OLV duration >90 min, lesser surgeon's experience and lower PEEP value.

TRIAL REGISTRATION
ChiCTR2300074649.
Spatial mapping of the HCC landscape identifies unique intratumoral perivascular-immune neighborhoods
Authors: Marsh-Wakefield Felix , Santhakumar Cositha , Ferguson Angela L. , Ashhurst Thomas M. , Shin Joo-Shik , Guan Fiona H.X. , Shields Nicholas J. , Platt Barry J. , Putri Givanna H. , Gupta Ruta , Crawford Michael , Pulitano Carlo , Sandroussi Charbel , Laurence Jerome M. , Liu Ken , McCaughan Geoffrey W. , Palendira Umaimainthan 
Published: October 2024

Background:
HCC develops in the context of chronic inflammation; however, the opposing roles the immune system plays in both the development and control of tumors are not fully understood. Mapping immune cell interactions across the distinct tissue regions could provide greater insight into the role individual immune populations have within tumors.

Methods:
A 39-parameter imaging mass cytometry panel was optimized with markers targeting immune cells, stromal cells, endothelial cells, hepatocytes, and tumor cells. We mapped the immune landscape of tumor, invasive margin, and adjacent nontumor regions across 16 resected tumors comprising 144 regions of interest. X-shift clustering and manual gating were used to characterize cell subsets, and Spectre quantified the spatial environment to identify cellular neighborhoods. Ligand-receptor communication was quantified on 2 single-cell RNA-sequencing data sets and 1 spatial transcriptomic data set.

Results:
We show immune cell densities remain largely consistent across these 3 regions, except for subsets of monocyte-derived macrophages, which are enriched within the tumors. Mapping cellular interactions across these regions in an unbiased manner identifies immune neighborhoods comprised of tissue-resident T cells, dendritic cells, and various macrophage populations around perivascular spaces. Importantly, we identify multiple immune cells within these neighborhoods interacting with VEGFA+ perivascular macrophages. VEGFA was further identified as a ligand for communication between perivascular macrophages and CD34+ endothelial cells.

Conclusions:
Immune cell neighborhood interactions, but not cell densities, differ between intratumoral and adjacent nontumor regions in HCC. Unique intratumoral immune neighborhoods around the perivascular space point to an altered landscape within tumors. Enrichment of VEGFA+ perivascular macrophages within these tumors could play a key role in angiogenesis and vascular permeability.
Post-translational modifications drive the effects of HMGB1 in alcohol-associated liver disease
Authors: Ge Xiaodong , Subramaniyam Nithyananthan , Song Zhuolun , Desert Romain , Han Hui , Das Sukanta , Komakula Sai Santosh Babu , Wang Chao , Lantvit Daniel , Ge Zhiyan , Hoshida Yujin , Nieto Natalia 
Published: October 2024

Background:
We previously identified that high-mobility group box-1 (HMGB1) is increased and undergoes post-translational modifications (PTMs) in response to alcohol consumption. Here, we hypothesized that specific PTMs, occurring mostly in hepatocytes and myeloid cells, could contribute to the pathogenesis of alcohol-associated liver disease (AALD).

Methods:
We used the Lieber-DeCarli (LD) model of early alcohol-induced liver injury, combined with engineered viral vectors and genetic approaches to regulate the expression of HMGB1, its PTMs (reduced [H], oxidized [O], acetylated [Ac], both [O + Ac]), and its receptors (RAGE, TLR4) in a cell-specific manner (hepatocytes and/or myeloid cells).

Results:

Hmgb1 ablation in hepatocytes or myeloid cells partially protected, while ablation in both prevented steatosis, inflammation, IL1B production, and alcohol-induced liver injury. Hepatocytes were a major source of [H], [O], and [Ac] HMGB1, whereas myeloid cells produced only [H] and [Ac] HMGB1. Neutralization of HMGB1 prevented, whereas injection of [H] HMGB1 increased AALD, which was worsened by injection of [O] HMGB1. While [O] HMGB1 induced liver injury, [Ac] HMGB1 protected and counteracted the effects of [O] HMGB1 in AALD. [O] HMGB1 stimulated macrophage (MF) migration, activation, IL1B production, and secretion. Ethanol-fed Rage
ΔMye but not Tlr4
ΔMye, Rage
ΔHep, or Tlr4
ΔHep mice were protected from AALD, indicating a crucial role of RAGE in myeloid cells for AALD. [O] HMGB1 recruited and activated myeloid cells through RAGE and contributed to steatosis, inflammation, and IL1B production in AALD.

Conclusions:
These results provide evidence for targeting [O] HMGB1 of hepatocyte origin as a ligand for RAGE signaling in myeloid cells and a driver of steatosis, inflammatory cell infiltration, and IL1B production in AALD. Importantly, we reveal that [Ac] HMGB1 offsets the noxious effects of [O] HMGB1 in AALD.
Individuals Who Had a Lifetime History of Suicide Attempts and Their Relationships With Inflammation, Severity of Depressive Symptoms, and Childhood Maltreatments
Authors: Bellinello Gisele de Souza Teixeira , Urbano Mariana , Vargas Heber Odebrecht , Verri Waldiceu , Rossaneis Ana Carolina , Odebrecht Vargas Nunes Sandra 
Published: October 2024

Abstract
Lifetime history of suicide attempts is associated with inflammatory mechanisms, severity of depressive symptoms, and childhood trauma. This cross-sectional study enrolled 54 suicide attempters and 154 nonsuicide attempters. All individuals were assessed through a questionnaire, a structured clinical interview, scales, anthropometric measures, and laboratory biomarkers. Individuals with a history of lifetime suicide attempts showed significant positive correlations regarding soluble tumor necrosis factor receptor 1 and severity of depressive symptoms (p = 0.013), interleukin-1 receptor antagonist and severity of depressive symptoms (p = 0.04), and absenteeism from work and childhood physical abuse (p = 0.012). Suicide attempters also experienced more childhood trauma (sexual abuse, physical abuse, emotional abuse, emotional neglect, and physical neglect) compared with nonsuicide attempters. IL-4 levels were significantly lower in individuals who attempted suicide than in nonsuicidal individuals. Lifetime suicide attempts in major affective disorders were associated with childhood trauma and proinflammatory and anti-inflammatory cytokines.
Alexithymia—A Neglected Factor Influencing Educational Satisfaction and Psychological Wellbeing in Medical Students
Authors: Simic Katarina , Latas Milan , Pantovic Stefanovic Maja , Nesic Milica 
Published: October 2024

Abstract
Alexithymia presents a reduced ability to identify, express, and describe one's own emotions. In medical professionals, alexithymia is associated with increased burnout and substance use, as well as reduced altruistic behavior. Our aim was to examine the association between alexithymia and different sociodemographic, psychological, and somatic parameters among medical students. Participants included 186 third- and sixth-year students of the Faculty of Medicine in Belgrade, Serbia. Data were collected through an online survey, composed of 1) a general questionnaire (sociodemographic data, education satisfaction, grade point average, presence of psychological and somatic disorders), 2) Twenty-Item Toronto Alexithymia Scale, 3) Patient Health Questionnaire-9, and 4) Beck Anxiety Inventory. Third-year students had significantly higher rates of alexithymia compared with sixth-year students. Negative correlation was found between alexithymia and educational satisfaction (r = −0.276**) and alexithymia and grade point average (r = −0.186*). A positive correlation was found between alexithymia and depression (r = 0.424**) and alexithymia and anxiety (r = 0.338**). The negative impact of alexithymia on educational satisfaction and psychological health is pronounced in the population of medical students, indicating a need for preventive programs aimed in medical schools.
Demoralization as a specifier for adjustment disorders
Authors: Kissane David 
Published: October 2024

Abstract
Adjustment disorder (AD) is the most common psychiatric diagnosis yet carries the most loosely defined diagnostic criteria. The phenomenology of demoralization (hopelessness, pointlessness, discouragement, and entrapment) enriches criteria for AD substantially. Moreover, demoralization mediates the suicidality that can follow from maladaptive coping. The focus of treatment seeks to restore morale, hope, and meaning as clear therapeutic targets. Use of demoralization as a “specifier” for AD introduces a subtype that will enhance understanding of and communication about a patient, while providing optimal treatment targets.
Large-cell Basaloid Adenocarcinoma of the Lung
Authors: Suster David , Mejbel Haider A. , Mackinnon Alexander Craig , Suster Saul 
Published: October 2024

A distinctive form of lung adenocarcinoma that closely mimics large-cell neuroendocrine carcinoma is described. The tumors arose in 6 women and 6 men aged 46–86 years (mean=58.4). They presented as peripheral subpleural masses measuring 2–12 cm (mean=6.5 cm). Histologically they were characterized by islands or anastomosing and serpiginous strands of large, atypical cells showing striking peripheral palisading of nuclei, with high mitotic activity and prominent comedo-like areas of necrosis. Because of the striking resemblance to neuroendocrine tumors, some of the cases were initially diagnosed as large-cell neuroendocrine carcinoma despite the absence of neuroendocrine markers. Immunohistochemistry showed positivity of the tumor cells for TTF1 and napsin-A, and negative staining for p40. The tumors were also uniformly negative for multiple neuroendocrine markers, including chromogranin, synaptophysin, CD56, and INSM1. Electron microscopy performed in 2 cases was negative for membrane-bound dense core neurosecretory granules. Pathogenic alterations were detected in 5 of 8 tumors tested by next-generation sequencing. Point mutations in KRAS and TP53 were identified in 5 patients. Low-level amplification of GNAS, KIT, and FGFR1 was present in 2 patients. No RB1 mutations were identified. Clinical follow-up in 10 cases showed that 2 patients died of their tumors, 2 experienced distant metastases, and 6 were alive and well from 1 to 13 years after diagnosis (median=7.1 y). Large-cell basaloid adenocarcinoma is an unusual variant of lung cancer that is easily confused with large-cell neuroendocrine carcinoma. Awareness of this unusual variant of lung adenocarcinoma is important for treatment and prognosis and for avoiding misdiagnosis.