bluuebunny/crossref_metadata_2025_split huggingface dataset:
Magrolimab plus rituximab with or without chemotherapy in patients with relapsed/refractory diffuse large B-cell lymphoma
Authors: Maakaron Joseph E. , Asch Adam , Popplewell Leslie , Collins Graham P. , Flinn Ian W. , Ghosh Nilanjan , Keane Colm , Ku Matthew , Mehta Amitkumar , Roschewski Mark , Hacohen-Kleiman Gal , Huo Yanan , Zhang Yi , Renard Camille , Smith Sonali M. , Advani Ranjana 
Published: September 2024

Abstract
Patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) ineligible for available salvage therapies have limited options for long-term disease control, necessitating novel treatments. Previously, magrolimab (anti–cluster-of-differentiation-47 antibody) plus rituximab (M+R) demonstrated ability to induce complete responses (CR) in R/R DLBCL. Here, we report 3-year follow-up data from this phase 1b/2 study assessing long-term safety and efficacy of M+R, and initial safety and efficacy of M+R plus gemcitabine-oxaliplatin (M+R-GemOx), in R/R DLBCL. After magrolimab priming, 4 groups of patients received M+R, 10 to 45 mg/kg magrolimab with 375 mg/m2 rituximab; patients receiving M+R-GemOx received 30 or 45 mg/kg magrolimab with 375 mg/m2 rituximab, 1000 mg/m2 gemcitabine, and 100 mg/m2 oxaliplatin. Primary end points were treatment-emergent adverse events (TEAEs) and objective response rate (ORR). Secondary end points included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Of 132 patients treated, 99 received M+R and 33 received M+R-GemOx. Most common any-grade TEAEs were fatigue (M+R, 40%; M+R-GemOx, 70%), infusion-related reactions (M+R, 39%), or anemia (M+R-GemOx, 70%). Treatment-related TEAEs led to magrolimab discontinuation in 7% (M+R) and 6% (M+R-GemOx). One death was considered treatment related (M+R-GemOx, colitis). M+R ORR was 24% (CR, 12%), and median DOR was 9.3 months. Median PFS and OS were 1.8 and 9.2 months, respectively. M+R-GemOx ORR was 52% (CR, 39%); 12-month DOR rate was 66.6% (95% confidence interval, 33.1-86.1). Median PFS and OS were 3.9 months and not reached, respectively. These results demonstrate that M+R with/without GemOx is well tolerated, and M+R-GemOx has clinical activity in patients with R/R DLBCL. This trial was registered at www.clinicaltrials.gov as #NCT02953509.
Risk of bleeding in patients with essential thrombocythemia and extreme thrombocytosis
Authors: Venkat Rathnam K. , Redd Robert A. , Harris Amyah C. , Aryee Martin J. , Marneth Anna E. , Kamaz Baransel , Kim Chulwoo J. , Wazir Mohammed , Weeks Lachelle D. , Stahl Maximilian , DeAngelo Daniel J. , Lindsley R. Coleman , Luskin Marlise R. , Hobbs Gabriela S. , How Joan 
Published: September 2024

Abstract
Approximately 25% of patients with essential thrombocythemia (ET) present with extreme thrombocytosis (ExT), defined as having a platelet count ≥1000 × 109/L. ExT patients may have an increased bleeding risk associated with acquired von Willebrand syndrome. We retrospectively analyzed the risk of bleeding and thrombosis in ExT vs non-ExT patients with ET at Dana-Farber Cancer Institute and Massachusetts General Hospital from 2014 to 2022 to inform treatment decisions. We abstracted the first major bleed, clinically relevant nonmajor bleed (CRNMB), and thrombotic events from medical records. We identified 128 ExT patients (28%) and 323 non-ExT patients (72%). Cumulative incidence of bleeding was not different in ExT vs non-ExT patients (21% vs 13% [P = .28] for major bleed; 16% vs 15% [P = .50] for CRNMB). Very low and low thrombotic risk ExT patients were more likely to be cytoreduced than very low- and low-risk non-ExT patients (69% vs 50% [P = .060] for very low risk; 83% vs 53% [P = .0059] for low risk). However, we found no differences in bleeding between ExT and non-ExT patients when restricting the risk of bleed from diagnosis to cytoreduction start date (28% vs 19% [P = .29] for major bleed; 24% vs 22% [P = .75] for CRNMB). Cumulative incidence of thrombosis was also not different between ExT and non-ExT patients (28% vs 25%; P = .98). This suggests that cytoreduction may not be necessary to reduce bleeding risk based only on a platelet count of 1 million. We identified novel risk factors for bleeding in patients with ET including diabetes mellitus and the DNMT3A mutation.
UM171 enhances fitness and engraftment of gene-modified hematopoietic stem cells from patients with sickle cell disease
Authors: Liu Boya , Klatt Denise , Zhou Yu , Manis John P. , Sauvageau Guy , Pellin Danilo , Brendel Christian , Williams David A. 
Published: September 2024

Abstract
Hematopoietic stem cell (HSC) transplantation with lentiviral vector (LVV)-transduced autologous cells has proven an effective therapeutic strategy for sickle cell disease (SCD). However, ex vivo culture or proliferative stress associated with in vivo reconstitution may amplify any underlying genetic risk of leukemia. We aimed to minimize culture-induced stress and reduce genomic damage during ex vivo culture and enhance stem cell fitness and reconstitution of SCD CD34+ cells transduced with BCL11A shmiR-encoding LVV. UM171, a pyrimidoindole derivative, can expand normal HSCs during in vitro culture and has been shown to be safe and effective using umbilical cord blood. We examined the effect of UM171 during ex vivo LVV transduction of SCD HSCs. Culture of SCD CD34+ HSCs with UM171 during transduction reduced DNA damage and reactive oxygen species, decreased apoptosis, and was associated with increased numbers of immunophenotypically defined long-term HSCs. UM171 increased the engraftment of LVV-transduced human HSCs in immunodeficient mice and barcode tracing revealed increased clonal diversity of engrafting cells. In competitive transplantation assays, analysis of bone marrow showed that cells transduced in the presence of UM171 consistently outcompeted those transduced under control conditions. In summary, exposure of SCD peripheral blood CD34+ cells to UM171 during LVV transduction enhances stem cell fitness. These findings suggest manufacturing of genetically modified HSCs in the presence of UM171 may improve efficacy, safety, and sustainability of gene therapy using ex vivo approaches. BCL11A shmiR-encoding LVV is in clinical trials to treat SCD (NCT03282656), UM171 is in clinical trials to culture umbilical cord blood (NCT02668315).
Occupation and SARS-CoV-2 in Europe: a review
Authors: Rhodes Sarah , Beale Sarah , Daniels Sarah , Gittins Matthew , Mueller William , McElvenny Damien , van Tongeren Martie 
Published: September 2024

IntroductionWorkplace features such as ventilation, temperature and the extent of contact are all likely to relate to personal risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Occupations relating to healthcare, social care, education, transport and food production and retail are thought to have increased risks, but the extent to which these risks are elevated and how they have varied over time is unclear.MethodsWe searched for population cohort studies conducted in Europe that compared coronavirus disease 2019 (COVID-19) outcomes between two or more different occupational groups. Data were extracted on relative differences between occupational groups, split into four time-periods corresponding to pandemic waves.ResultsWe included data from 17 studies. 11 studies used SARS-CoV-2 as their outcome measure and six used COVID-19 hospitalisation and mortality. During waves one and two, the majority of studies saw elevated risks in the five groups that we looked at. Only seven studies used data from wave three onwards. Elevated risks were observed in waves three and four for social care and education workers in some studies.ConclusionsEvidence relating to occupational differences in COVID-19 outcomes in Europe largely focuses on the early part of the pandemic. There is consistent evidence that the direction and magnitude of differences varied with time. Workers in the healthcare, transport and food production sectors saw highly elevated risks in the early part of the pandemic in the majority of studies but this did not appear to continue. There was evidence that elevated risks of infection in the education and social care sectors may have persisted.
Low-dose pro-resolving mediators temporally reset the resolution response to microbial inflammation
Authors: Serhan Charles N. , Chiang Nan , Nshimiyimana Robert 
Published: September 2024

Abstract
Background
Specialized pro-resolving mediators (SPMs) promote resolution of inflammation, clear infections and stimulate tissue regeneration. These include resolvins, protectins, and maresins. During self-resolving acute inflammation, SPMs are produced and have key functions activating endogenous resolution response for returning to homeostasis. Herein, we addressed whether infections initiated with ongoing inflammation alter resolution programs, and if low-dose repetitive SPM regimen re-programs the resolution response.

Methods
Inflammation was initiated with zymosan (1 mg/mouse) followed by E. coli (105 CFU/mouse) infections carried out in murine peritonitis, and exudates collected at 4-72 h. Leukocytes were enumerated using light microscopy, percentages of PMN, monocytes and macrophages were determined using flow cytometry, and resolution indices calculated. Lipid mediators and SPM profiles were established using mass spectrometry-based metabololipidomics. Repetitive dosing with a SPM panel consisting of RvD1, RvD2, RvD5, MaR1 and RvE2 (0.1 ng/mouse each, i.p.) was given to mice, followed by zymosan challenge. Leukocyte composition, resolution indices and RNA-sequencing were carried out for the repetitive SPM treatments.

Results
E. coli infections initiated acute inflammation-resolution programs with temporal SPM production in the infectious exudates. Zymosan-induced inflammation prior to E. coli peritonitis shifted exudate resolution indices and delayed E. coli clearance. Lipid mediator metabololipidomics demonstrated that E. coli infection with ongoing zymosan-induced inflammation shifted the time course of exudate SPMs, activating a SPM cluster that included RvD1, RvD5 and MaR1 during the initiation phase of infectious inflammation (0-4 h); RvD5 and MaR1 were present also in the resolution phase (24-48 h). To emulate daily SPM regimens used in humans, a repetitive subthreshold dosing of the SPM panel RvD1, RvD2, RvD5, MaR1 and RvE2 each at 0.1 ng per mouse was administered. This low-dose SPM regimen accelerated exudate PMN clearance following zymosan-induced inflammation, and shortened the resolution interval by > 70%. These low-dose SPMs regulated genes and pathways related to immune response, chemokine clearance and tissue repair, as demonstrated by using RNA-sequencing.

Conclusions
Infections encountered during ongoing inflammation in mice reset the resolution mechanisms of inflammation via SPM clusters. Low-dose SPMs activate innate immune responses and pathways towards the resolution response that can be reprogrammed.
Risk of suicide after hospitalizations due to acute physical health conditions—a cohort study of the Norwegian population
Authors: Asheim Andreas , Nilsen Sara Marie , Svedahl Ellen Rabben , Kaspersen Silje L. , Bjerkeset Ottar , Janszky Imre , Bjørngaard Johan Håkon 
Published: September 2024

Abstract
Background
It is well known that individuals recently discharged from psychiatric inpatient care face a high risk of suicide. Severe physical health conditions have also been linked to suicide risk. The risk of suicide following discharge from somatic hospitals is not known for individuals admitted due to acute physical health conditions.

Methods
A Cohort study using data from the entire Norwegian population aged 12 years and older from 2008 to 2022 linked with information on health service use and cause of death. We used Cox regression with age as time axis to estimate sex-adjusted hazard ratios of suicide following discharge for ages 12 to 64 years and 65 years and older. We also performed analyses after excluding hospitalizations with indications of concurrent mental disorders, self-harm, or suicide attempts. To assess individual risk, we performed an adapted case-crossover analysis among discharged patients who died from suicide.

Results
A total of 4 632,980 individuals aged 12 to 64 years and 1,469,265 individuals aged 65 years and older were included. Compared to unexposed individuals at similar ages, we found an increased risk of suicide in the first 4 weeks after discharge, with a hazard ratio (HR) of 7.0 (95% confidence interval (CI) 5.9 to 8.3) among those aged 12 to 64 years and 6.8 (95% CI 5.4 to 8.6) among those 65 years and older. In the younger age group, the risk was attenuated, with a HR of 2.4 (95% CI 1.7 to 3.2) after excluding hospitalizations with indications of concurrent mental disorders, self-harm, or suicide attempts. The corresponding HR was 4.8 (95% CI 3.5 to 6.4) among those 65 years and older, declining to 1.9, (1.2 to 3.1) in weeks 5 to 8 and 1.2 (0.7 to 2.2) in weeks 21 to 24. The case-crossover analysis confirmed that individuals 65 years and older were particularly vulnerable.

Conclusions
The heightened risk of suicide following discharge from acute somatic hospitalization, even in the absence of concurrent mental disorders, self-harm, or prior suicide attempts, underscores the critical need for comprehensive mental health and existential support for patients post-discharge.
CCL5 is essential for axonogenesis and neuronal restoration after brain injury
Authors: Ho Man-Hau , Tsai Yih-Jeng , Chen Chia-Yen , Yang Anastasia , Burnouf Thierry , Wang Yun , Chiang Yung-Hsiao , Hoffer Barry J. , Chou Szu-Yi 
Published: September 2024

Abstract
Background
Traumatic brain injury (TBI) causes axon tearing and synapse degradation, resulting in multiple neurological dysfunctions and exacerbation of early neurodegeneration; the repair of axonal and synaptic structures is critical for restoring neuronal function. C-C Motif Chemokine Ligand 5 (CCL5) shows many neuroprotective activities.

Method
A close-head weight-drop system was used to induce mild brain trauma in C57BL/6 (wild-type, WT) and CCL5 knockout (CCL5-KO) mice. The mNSS score, rotarod, beam walking, and sticker removal tests were used to assay neurological function after mTBI in different groups of mice. The restoration of motor and sensory functions was impaired in CCL5-KO mice after one month of injury, with swelling of axons and synapses from Golgi staining and reduced synaptic proteins-synaptophysin and PSD95. Administration of recombinant CCL5 (Pre-treatment: 300 pg/g once before injury; or post-treatment: 30 pg/g every 2 days, since 3 days after injury for 1 month) through intranasal delivery into mouse brain improved the motor and sensory neurological dysfunctions in CCL5-KO TBI mice.

Results
Proteomic analysis using LC-MS/MS identified that the “Nervous system development and function”-related proteins, including axonogenesis, synaptogenesis, and myelination signaling pathways, were reduced in injured cortex of CCL5-KO mice; both pre-treatment and post-treatment with CCL5 augmented those pathways. Immunostaining and western blot analysis confirmed axonogenesis and synaptogenesis related Semaphorin, Ephrin, p70S6/mTOR signaling, and myelination-related Neuregulin/ErbB and FGF/FAK signaling pathways were up-regulated in the cortical tissue by CCL5 after brain injury. We also noticed cortex redevelopment after long-term administration of CCL5 after brain injury with increased Reelin positive Cajal-Rerzius Cells and CXCR4 expression. CCL5 enhanced the growth of cone filopodia in a primary neuron culture system; blocking CCL5’s receptor CCR5 by Maraviroc reduced the intensity of filopodia in growth cone and also CCL5 mediated mTOR and Rho signalling activation. Inhibiting mTOR and Rho signaling abolished CCL5 induced growth cone formation.

Conclusions
CCL5 plays a critical role in starting the intrinsic neuronal regeneration system following TBI, which includes growth cone formation, axonogenesis and synaptogensis, remyelination, and the subsequent proper wiring of cortical circuits. Our study underscores the potential of CCL5 as a robust therapeutic stratagem in treating axonal injury and degeneration during the chronic phase after mild brain injury.

Graphical Abstract
Qualitative assessment of evidence-informed adolescent mental health policymaking in India: insights from project SAMA
Authors: Ivory Alice , Arelingaiah Mutharaju , Janardhana Navaneetham , Bhola Poornima , Hugh-Jones Siobhan , Mirzoev Tolib 
Published: September 2024

Abstract
Background
The importance of evidence-informed health policymaking is widely recognized. However, many low- and middle-income countries lack evidence-informed mental health policies due to insufficient data, stigma or lack of resources. Various policies address adolescent mental health in India, but published knowledge on their evidence-informed nature is limited. In this paper, we report results of our analysis of the role of evidence in adolescent mental health policymaking in India.

Methods
This paper reports findings from the document analysis of key policy documentation (n = 10) and in-depth interviews with policy actors including policymakers, researchers, practitioners and intermediaries (n = 13). Framework analysis was used, informed by the components of a conceptual framework adapted from the literature: actors, policy and evidence processes, nature of evidence itself and contextual influences.

Results
Results show that adolescent mental health policies in India were generally evidence-informed, with more key evidence becoming generally available from 2010 onwards. Both formal and informal evidence informed mental health policies, particularly agenda-setting and policy development. Mental health policymaking in India is deemed important yet relatively neglected due to competing policy priorities and structural barriers such as stigma. Use of evidence in mental health policymaking reflected differing values, interests, relative powers and ideologies of policy actors. Involvement of government officials in evidence generation often resulted in successful evidence uptake in policy decisions. Policy actors often favoured formal and quantitative evidence, with a tendency to accept global evidence that aligns with personal values.

Conclusions
There is a need to ensure a balanced and complementary combination of formal and informal evidence for policy decisions. Evidence generation, dissemination and use for policy processes should recognize evidence preferences by key stakeholders, while prioritizing locally available evidence where possible. To help this, a balanced involvement of policy actors can ensure complementary perspectives in evidence production and policy agendas. This continued generation and promotion of evidence can also help reduce societal stigma around mental health and promote mental health as a key policy priority.
Do calorie labels change energy purchased in a simulated online food delivery platform? A multi-arm randomised controlled trial
Authors: Luick Madison , Bianchi Filippo , Bain Francis , Bandy Lauren , Doshi Parita , Hilliard Darren , Leung Jovita , Mottershaw Abigail , Stuijfzand Bobby , Whitwell-Mak Jordan , Jebb Susan A. , Harper Hugo , Pechey Rachel 
Published: September 2024

Abstract
Background
As rates of obesity and overweight continue to increase in the UK, calorie labels have been introduced on menus as a policy option to provide information to consumers on the energy content of foods and to enable informed choices. This study tested whether the addition of calorie labels to items in a simulated food delivery platform may reduce the energy content of items selected.

Methods
UK adults (n = 8,780) who used food delivery platforms were asked to use the simulated platform as they would in real life to order a meal for themselves. Participants were randomly allocated to a control condition (no calorie labels) or to one of seven intervention groups: (1) large size calorie labels adjacent to the price (LP), (2) large size label adjacent to the product name (LN), (3) small label adjacent to price (SP), (4) small label adjacent to product name (SN), (5) LP with a calorie label switch-off filter (LP + Off), (6) LP with a switch-on filter (LP + On), or, (7) LP with a summary label of the total basket energy content (LP + Sum). Regression analysis assessed the impact of calorie labels on energy content of foods selected compared to the control condition.

Results
The mean energy selected in the control condition was 1408 kcal (95%CI: 93, 2719). There was a statistically significant reduction in mean energy selected in five of the seven intervention trial arms (LN labels (-60 kcal, 95%CI: -111, -6), SN (-73, 95%CI: -125, -19), LP + Off (-110, 95%CI: -161, -57), LP + On (-109, 95%CI: -159, -57), LP + Sum (-85 kcal, 95%CI: -137, -30). There was no evidence the other two conditions (LP (-33, 95%CI: -88, 24) and SP (-52, 95%CI: -105, 2)) differed from control. There was no evidence of an effect of any intervention when the analysis was restricted to participants who were overweight or obese.

Conclusion
Adding calorie labels to food items in a simulated online food delivery platform reduced the energy content of foods selected in five out of seven labelling scenarios. This study provides useful information to inform the implementation of these labels in a food delivery platform context.
Nutraceuticals and pharmacological to balance the transitional microbiome to extend immunity during COVID-19 and other viral infections
Authors: Kaushal Anju 
Published: September 2024

Abstract
Scope
The underlying medical conditions and gut dysbiosis is known to influence COVID-19 severity in high-risk patients. The current review proposed the optimal usage of nutraceuticals & pharmacological interventions can help regulate the protective immune response and balance the regulatory functionality of gut microbiota.

Summary
Many studies have revealed that the probiotic interventions viz., Lactobacillus rhamnosus, L. plantarum & other bacterial spp. reduce IFNγ & TNF-α and increase IL-4 & IL-10 secretions to control the immunostimulatory effects in upper respiratory tract infection. Dietary fibres utilized by beneficial microbiota and microbial metabolites can control the NF-kB regulation. Vitamin C halts the propagation of pathogens and vitamin D and A modulate the GM. Selenium and Flavonoids also control the redox regulations. Interferon therapy can antagonize the viral replications, while corticosteroids may reduce the death rates. BCG vaccine reprograms the monocytes to build trained immunity. Bifidobacterium and related microbes were found to increase the vaccine efficacy. Vaccines against COVID-19 and season flu also boost the immunity profile for robust protection. Over all, the collective effects of these therapeutics could help increase the opportunities for faster recovery from infectious diseases.

Conclusion
The nutraceutical supplements and pharmacological medicines mediate the modulatory functionalities among beneficial microbes of gut, which in turn eliminate pathogens, harmonize the activity of immune cells to secrete essential regulatory molecular receptors and adaptor proteins establishing the homeostasis in the body organs through essential microbiome. Therefore, the implementation of this methodology could control the severity events during clinical sickness and reduce the mortalities.