bluuebunny/crossref_metadata_2025 huggingface dataset:
P22.05.B DIFFERENCES IN END-OF-LIFE CARE AND PLACE OF DEATH IN PATIENTS WITH MALIGNANT BRAIN TUMOUR: A SWEDISH REGISTRY STUDY
Authors: Ozanne A , Öhlén J , Nyblom S , Jakola A S , Smits A , Larsdotter C
Published: October 2024

BACKGROUND

The treatment in malignant brain tumour is multimodal and consists of a combination of surgery, radiotherapy, and chemotherapy. The average survival differs depending on e.g. degree of malignancy and location. Potential palliative needs also need attention. This preliminary study seeks to utilize registry data to identify the place of death among adult people with malignant brain tumours in Sweden between 2013 and 2019. It aims to explore potential associations between the place of death and factors such as medical diagnosis, official palliative care status, sociodemographic characteristics, health service utilization, and healthcare service characteristics at the end-of-life.

MATERIAL AND METHODS

This is a population-level registry study examined the place of death among adults who died of malignant brain tumours in Sweden. Data was retrieved from the Swedish National board of Health and Welfare (NBHW), the Swedish Register of Palliative Care (SRCP), and Statistics Sweden (SCB). Descriptive statistics, univariable and multivariable binary logistic regression analyses are performed.

RESULTS

Preliminary results show that 3888 adults died of malignant brain tumours between 2013 and 2019 (41.4% female). In total, 64.4% did not have the palliative care diagnosis Z51.5, and this percentage varied depending on location of their death. Additionally, 57.2% did not have access to specialised palliative care at their place of death. Notably, among those who died in a nursing home, 80.0% lacked this access. Among those who died in a hospital, 53.5% had experienced one transfer to the hospital in the last month of life, and 41.8% had undergone two or more transfers. Notably, the odds ratio of dying in a hospital versus at home was higher for patients with more transfers. Additionally, the odds ratio of dying in a hospital compared to dying at home was higher in the Stockholm region but lower in the Western, South-eastern, and the Southern regions.

CONCLUSION

A minority of patients had access to specialised palliative care, despite being diagnosed with a malignant brain tumour, and this varied depending on the location of their death. Moreover, notable regional disparities were observed between deaths that occurred in hospitals versus at home. These findings underscore the presence of unequal End-of-life palliative care and highlights the need for additional investigation.
P26.03.B AN INTERNATIONAL ACCELERATOR PROGRAMME FOR NOVEL BRAIN TUMOUR THERAPIES
Authors: Aitken C K , Huskens N , Bushby K , Noble K , Hamerlik P , Kobayashi D , Mathew R , McCall J , Plummer R , Rahman R , Lopez J
Published: October 2024

BACKGROUND

Developing a comprehensive translational programme for brain tumours involves navigating numerous challenges, including robustness of preclinical studies, clinical trial design, safety, understanding and addressing regulatory requirements, and commercialisation. Recognising the difficulty of this journey, the Brain Tumour Research Novel Therapeutics Accelerator (BTR-NTA) was launched in 2023. The BTR-NTA is an accelerator programme providing independent expert guidance to de-risk drug or device development through systematic evaluation. The international, multidisciplinary BTR-NTA Committee spans expertise across the entire therapeutic development pipeline. Supported by Brain Tumour Research, the BTR-NTA programme is free for academic groups and available for a nominal meeting contribution fee for industry applicants.

MATERIAL AND METHODS

Researchers at any stage of therapeutic development may apply to BTR-NTA. Accepted applicants proceed as follows: 1. Applicants outline their current and prospective data and findings. The proposal and all supporting materials are covered under a confidentiality agreement that protects applicants’ intellectual property; 2. Proposals are reviewed by the BTR-NTA Committee; 3. Applicants and BTR-NTA Committee meet in-person to constructively evaluate the work; and 4. Applicants receive a comprehensive report with feedback on strengths, identification of potential risks, and guidance on next steps. The BTR-NTA Committee dedicates time for in-person meetings with each applicant, and extensive time pre- and post-meeting.

RESULTS

Since the launch of the BTR-NTA in 2023,13 international research groups have applied to the programme and three therapeutic applications have been advanced to the in-person review by the BTR-NTA Committee. Of the applicants who provided feedback on the BTR-NTA programme, all intended to adjust or refine their future work based on the BTR-NTA Committee’s input and the average rating of the programme’s helpfulness was 9.5 out of 10.

CONCLUSION

BTR-NTA reviews will continue to take place bi-annually, with capacity to provide support for up to four research groups per review. The ultimate goal of the BTR-NTA is to help researchers with a potential therapy for brain tumours navigate the development journey and reach the clinic in an efficient way. This programme will support development of novel therapies to improve outcomes for patients with brain tumours.
P26.06.B EVALUATION OF THE ANTITUMOR EFFECT OF A CHEMOTHERAPY-LOADED DEVICE FOR THE TREATMENT OF PRIMARY BRAIN TUMORS
Authors: Déry L , Charest G , Guérin B , Akbari M , Fortin D
Published: October 2024

BACKGROUND

Glioblastoma (GBM) is the most frequent and aggressive primary brain tumor in adults. It is characterized by its infiltration of the brain parenchyma, making complete surgical resection impossible. It is also resistant to radio-chemotherapy. Tumor recurrence is therefore inevitable, and median survival is just over 14 months. The location of these tumors also means that they are protected from chemotherapy by the presence of the blood-brain barrier (BBB). Currently available treatments are inadequate and do not provide optimal tumor control. We believe that treatment localized directly at the tumor site will eliminate a greater number of infiltrating tumor cells while significantly reducing systemic toxicity.

MATERIAL AND METHODS

For this project, we are collaborating with a team specializing in bioengineering, who have produced a biomaterial enabling the gradual release of various agents. Our aim is to use this biomaterial to deliver chemotherapeutic agents to the tumor site through the surgical cavity. We evaluated the antitumor potential of biomaterial loaded with different chemotherapies. Cell-based assays were carried out using glial tumor cells in the presence of the biomaterial containing chemotherapeutics. Cell viability readings were taken at different times to observe the antitumor effect of the selected neoplastic agents. A survival study was realized with the Fischer F98 rat model, which underwent partial tumor resection followed by injection of biomaterial containing chemotherapy. Histological studies of brains and resected tissues were carried out to assess the effect of the biomaterial on the brain environment.

RESULTS

In vitro assays showed a strong cytotoxic effect against glial tumor cells at 24h, 48h and 72h of biomaterial-drug incubation. The combination of two chemotherapeutic agents showed the best cytotoxic effect on glial tumor cells. We also performed a partial tumor resection and insertion of the chemotherapy-loaded biomaterial into the surgical cavity of the F98 glioma bearing rat. Similar to in vitro studies, the combination of two antineoplastic agents shows a significant improvement in animal survival.

CONCLUSION

In conclusion, the in vitro and in vivo results of this study show that the combination of chemotherapy has the greatest antitumor effect. We hope that these exciting results will lead to the development of a new treatment for patients with glioblastoma and potentially other diseases where complete tumor resection is impossible.

SUPPORT/ DISCLOSER

Funding was provided by donations and scholarships: La rose des vents, Fondation du Centre Hospitalier Universitaire de Sherbrooke (CHUS), Centre de recherche du CHUS (CRCHUS), Centre d’imagerie moléculaire de Sherbrooke (CIMS) and Centre d’excellence en Neurosciences de l’Université de Sherbrooke (CNS). All authors declare that they have no competing financial interests.
P26.14.B VITAMIN D3 ENHANCES TEMOZOLOMIDE EFFICACY IN GLIOBLASTOMA CELLS WHILE PROTECTING NORMAL ASTROCYTES: INVESTIGATING THE EFFECTS OF ADJUNCTIVE THERAPY
Authors: Morelli M , Di Lorenzo F , Nannipieri F , Trasciatti S , Di Stefano A , Lessi F , Mazzanti C
Published: October 2024

BACKGROUND

Glioblastoma (GB), the most aggressive brain tumor, poses challenges due to resistance to temozolomide (TMZ) and radiotherapy. Regorafenib (REGO) is used as second-line treatment for recurrences. Recent studies suggest potential benefits of using vitamin D, particularly cholecalciferol (VitD3), as adjunctive therapy in GB treatment, showing anti-proliferative effects and enhanced drug effectiveness. However, differences in the mechanisms of action between VitD3 and its active form, 1,25(OH)D3, require further investigation.

MATERIAL AND METHODS

Three commercial GB cell lines (U118, T98G, U87), and normal Human Brain Astrocytes (HBA) were treated for 48 hours with VitD3 and 1,25(OH)D3 at concentrations of 0, 3, 30, and 300 µM, and 0, 1, 10, and 100 nM, respectively along with TMZ and REGO at concentrations of 0, 10, 100, and 500 µM, and 0, 10, 20, 50 µM, respectively. Additionally, REGO with or without VitD3 was tested on tissue-derived primary cell cultures. Cellular responses to treatments in terms of cell proliferation were assessed using WST-1 and Crystal Violet assays.

RESULTS

VitD3 significantly reduced cell viability and proliferation in commercial tumor cell lines but not in healthy cell lines. Moreover, treatment with 10 and 100 µM of TMZ along with VitD3 resulted in an additional decrease in cell proliferation in commercial cell lines but not in healthy HBA. Conversely, REGO treatment did not further reduce proliferation with increasing VitD3 concentrations in tumor cell lines, HBA, or primary cultures. It is noteworthy that primary cultures exhibited greater resistance to REGO and/or VitD3 treatment compared to commercial cell lines. At all tested concentrations, 1,25(OH)D3 did not significantly reduce proliferation, either alone or with TMZ.

CONCLUSION

VitD3 unexpectedly enhances TMZ toxicity in tumor cell lines and may have a protective effect on healthy astrocytes in the presence of TMZ, suggesting potential as adjunctive therapy with existing TMZ chemotherapy, pending further understanding of the underlying molecular mechanisms. The efficacy of its active form requires testing at higher concentrations.
P27.27.A TUMOR TREATING FIELDS (TTFIELDS) THERAPY IN PATIENTS WITH GLIOBLASTOMA: LONG-TERM SURVIVAL RESULTS FROM TTFIELDS IN GERMANY IN ROUTINE CLINICAL CARE (TIGER) STUDY
Authors: Bähr O , Tabatabai G , Fietkau R , Goldbrunner R , Glas M
Published: October 2024

BACKGROUND

Tumor Treating Fields (TTFields) therapy has demonstrated significant improvements in overall survival (OS) and progression-free survival (PFS) when applied with adjuvant temozolomide (TMZ) compared to TMZ alone in newly diagnosed glioblastoma (ndGBM). TTFields therapy delivers electric fields, through scalp-placed arrays, that disrupt cellular processes critical for cancer cell viability, is CE marked for WHO grade 4 glioma, and is a recommended treatment regimen for ndGBM. TTFields therapy was administered to >25,000 patients, showing no systemic toxicities and mild to moderate skin reactions being the main therapy-related adverse event. Here, we report survival and safety data from the TIGER study, the largest prospective study investigating real-world use of TTFields therapy during routine clinical care in patients with ndGBM in Germany.

MATERIAL AND METHODS

TIGER (NCT03258021), a prospective, non-interventional, multicenter, medical device study, screened patients ≥18 years of age with histologically confirmed ndGMB from August 2017 to November 2019 in 81 participating centers in Germany who had clinical indication for TTFields therapy and were within the first 3 cycles of maintenance chemotherapy treatment. The analysis presented here focuses on patients that accepted TTFields therapy. Endpoints included OS, PFS, safety, and quality of life.

RESULTS

In this study, 710 assessed patients agreed to participate, with 583 (82%) opting for TTFields therapy, and 429 actually commencing the treatment. This patient population represents typical GBM patients, with a median age of 58 (range 19-82) and 64.1% being male. After a total follow-up of 56.2 months, the median OS and PFS were 19.6 months (95% CI, 17.9-22.4) and 10.2 months (95% CI, 9.4-11.4), respectively. The corresponding 1, 2, 3, and 4-year OS rates stood at 79.2%, 42.4%, 31.5%, and 27.7%, while the PFS rates were 42.0%, 23.2%, 19.9%, and 17.6%, respectively. Serious AEs were observed in 68% of patients, with only 0.5% being attributed to TTFields therapy.

CONCLUSION

TIGER is the largest prospective study to date on routine clinical practice in ndGBM. It reaffirms TTFields therapy’s positive safety profile, and its OS and PFS survival benefits are consistent with prior reports. It also reveals promising long-term survival rates.
Primary purulent bacterial pericarditis due to Streptococcus intermedius in the absence of an esophago-pericardial fistula
Authors: Patel Sahil M , Venkatesan Varshini , Simon Elaine , Hull Stephen
Published: October 2024

Purulent bacterial pericarditis is a rare and progressive infection with a high mortality. It is rarely due to Streptococcus intermedius, a commensal bacteria found in the oral cavity, gastrointestinal tract, and the genitourinary tract. Here we present a 71-year-old man with history of esophageal adenocarcinoma, status post distal esophagectomy and proximal gastrectomy 2 years prior, who developed cardiac tamponade secondary to primary S. intermedius purulent bacterial pericarditis in the absence of an esophago-pericardial fistula. We discuss the clinical manifestations of bacterial pericarditis and pericardial effusions, useful diagnostic tools, and explore possible mechanisms for S. intermedius pericarditis infection. This case highlights the importance of prompt suspicion, recognition, and intervention for bacterial pericarditis and cardiac tamponade in the setting of recent esophageal instrumentation. In addition, despite being rare, S. intermedius should be recognized as a possible pathogen in purulent bacterial pericarditis even with the absence of an esophago-pericardial fistula.
Palbociclib plus aromatase inhibitors in patients with metastatic breast cancer and cardiovascular diseases: real-world effectiveness
Authors: Brufsky Adam , Liu Xianchen , Li Benjamin , McRoy Lynn , Chen Connie , Makari Doris , Layman Rachel M , Rugo Hope S
Published: October 2024

Background

Patients with cardiovascular disease (CVD) comorbidities are often excluded from participating in breast cancer clinical trials. Consequently, data to inform treatment decisions for patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2−) metastatic breast cancer (mBC) and CVD are limited.

Objective

We compared the effectiveness of first-line palbociclib plus an aromatase inhibitor (AI) vs an AI alone and evaluated palbociclib treatment patterns in patients with HR+/HER2− mBC and CVD in routine clinical practice.

Methods

Data from the Flatiron Health Analytic Database were captured for patients with HR+/HER2− mBC and CVD who initiated first-line treatment with palbociclib plus an AI or an AI alone between February 2015 and March 2020 (data cutoff: September 30, 2020). Overall survival (OS), real-world progression-free survival (PFS), and treatment patterns were evaluated.

Results

Of the 469 patients with identifiable CVD, 160 received palbociclib plus an AI, and 309 received an AI alone. After stabilized inverse probability treatment weighting, both median OS (40.7 vs 26.5 months; hazard ratio [HR], 0.732 [95% CI, 0.537-0.997]; P = .048) and median real-world PFS (20.0 vs 12.5 months; HR, 0.679 [95% CI, 0.512-0.900]; P = .007) were significantly prolonged in patients treated with palbociclib plus an AI vs an AI alone. Among patients with a documented palbociclib starting dose, 78.5% started palbociclib at 125 mg/day, and 38.6% experienced dose adjustment.

Conclusions

In this real-world analysis, first-line palbociclib plus an AI was associated with improved effectiveness compared with an AI alone in patients with HR+/HER2– mBC and CVD.

Trial Registration

NCT05361655 (ClinicalTrials.gov)
Climate action on the mind: a longitudinal study of Americans’ psychosocial drivers of high-impact climate behaviors
Authors: Rakhimov Rakhim , Aweko Scovia , Thulin Erik
Published: October 2024

Widespread adoption of high-impact climate-positive behaviors can significantly reduce greenhouse gas emissions. To motivate these behaviors, social scientists and policymakers need to understand people’s psychological and social (psychosocial) factors to create an environment that encourages widespread adoption. Past longitudinal survey research has focused on tracking changes in broad climate change beliefs and attitudes, risk perceptions, and climate policy support. While behavioral and psychological research has identified key beliefs and attitudes as enabling conditions, this work tends to study a single snapshot in time, often in a narrow population, not allowing for the identification of trends. In the present paper, we launch the annual Climate Action on the Mind (CAM) longitudinal survey, which aims to track key psychosocial factors shown to be important enablers of climate behaviors. Our work focuses on behaviors relevant to households in the United States, such as installing solar panels and driving an electric vehicle. The paper introduces the first two waves of the CAM survey from December 2021 (n = 2031) and June 2023 (n = 1528), quota-matched to represent the US adult population on key demographics. Our research offers novel insights into how the enabling psychological conditions for high-impact climate-positive behaviors are shifting in the United States, helping to inform the development of future communication strategies, interventions, and climate policy.
Stomatal closure as a driver of minimum leaf conductance declines at high temperature and vapor pressure deficit in Quercus
Authors: Zailaa Joseph , Scoffoni Christine , Brodersen Craig R
Published: October 2024

Rising global temperatures and vapor pressure deficits (VPDs) are increasing plant water demand and becoming major drivers of large-scale plant mortality. Controlling transient leaf water loss after stomatal closure (minimum stomatal conductance [gmin]) is recognized as a key trait determining how long plants survive during soil drought. Yet, substantial uncertainty remains regarding how gmin responds to elevated temperatures and VPD and the underlying mechanisms. We measured gmin in 24 Quercus species from temperate and Mediterranean climates to determine whether gmin was sensitive to a coupled temperature and VPD increase. We also explored mechanistic links to phenology, climate, evolutionary history, and leaf anatomy. We found that gmin in all species exhibited a nonlinear negative temperature and VPD dependence. At 25 °C (VPD = 2.2 kPa), gmin varied from 1.19 to 8.09 mmol m−2 s−1 across species but converged to 0.57 ± 0.06 mmol m−2 s−1 at 45 °C (VPD = 6.6 kPa). In a subset of species, the effect of temperature and VPD on gmin was reversible and linked to the degree of stomatal closure, which was greater at 45 °C than at 25 °C. Our results show that gmin is dependent on temperature and VPD, is highly conserved in Quercus species, and is linked to leaf anatomy and stomatal behavior.
Art for health’s sake or health for art’s sake: Disentangling the bidirectional relationships between arts engagement and mental health
Authors: Mak Hei Wan , Hu Yang , Bu Feifei , Bone Jessica K , Fancourt Daisy
Published: October 2024

Increasing evidence links arts engagement with mental health, but the directionality of the link remains unclear. Applying a novel approach to causal inference, we used nonrecursive instrumental variable models to analyze two waves of data from the United Kingdom Household Longitudinal Study (n = 17,927). Our findings reveal bidirectional causal relationships between arts engagement (arts participation, cultural attendance, and heritage visits) and mental health (GHQ-12 mental distress and SF-12 Mental Component Summary mental well-being). After adjusting for time 1 measures and identifying confounders, cultural attendance and heritage visits were reciprocally associated with mental distress and mental well-being, while arts participation was only reciprocally associated with mental well-being. The bidirectional effects between arts engagement and mental health are modest but clearly demonstrated not only from mental health to arts but also from arts to mental health. Our findings indicate that previous evidence of an association between arts engagement and mental health is due to bidirectional causal effects. Interventions that boost arts participation, cultural attendance, and heritage visits may help break the negative feedback loop and enhance mental health.
A beautiful face is good when we’re judged by others, a moral character is better
Authors: Baum Julia , Abdel Rahman Rasha
Published: October 2024

Moral beauty, reflected in one’s actions, and facial beauty both affect how we’re judged. Here, we investigated how moral and facial beauty interactively affect social judgments and emotional responses, employing event-related brain potentials. Participants (all female) associated positive, neutral, or negative verbal information with faces scoring high or low on attractiveness and performed ratings of the faces as manipulation checks. In a separate test phase, the faces were presented again, and participants made valenced social judgments of the persons. Results show a dominance of moral beauty in valenced social judgments as well as ERPs related to reflexive and evaluative emotional responses (early posterior negativity, EPN, late positive potential, LPP), whereas facial attractiveness mattered little. In contrast, facial attractiveness affected visual processing (N170). Similarly, relatively shallow impressions of attractiveness and likability that require no knowledge about the person were influenced by both facial attractiveness and social-emotional information. This pattern of dominant effects of social-emotional information regardless of attractiveness shows that when it comes to our emotional responses and social judgments, moral beauty is what matters most, even in the face of physical beauty.
Disgust-specific impairment of facial emotion recognition in Parkinson’s disease patients with mild cognitive impairment
Authors: Chiang Ke-Wei , Tan Chun-Hsiang , Hong Wei-Pin , Yu Rwei-Ling
Published: October 2024

This study investigated the association between cognitive function and facial emotion recognition (FER) in patients with Parkinson’s disease (PD) and mild cognitive impairment (PD-MCI). We enrolled 126 participants from Taiwan, including 63 patients with idiopathic PD and 63 matched healthy controls. The PD group was divided into two groups: those with normal cognitive function (PD-NC) and those with MCI (PD-MCI). Participants underwent a modality emotion recognition test and comprehensive cognitive assessment. Our findings reveal that patients with PD-MCI exhibit significantly impaired FER, especially in recognizing “disgust,” compared with patients with PD-NC and healthy adults (P = .001). This deficit correlates with executive function, attention, memory, and visuospatial abilities. Attention mediates the relationship between executive function and “disgust” FER. The findings highlight how patients with PD-MCI are specifically challenged when recognizing “disgust” and suggest that cognitive training focusing on cognitive flexibility and attention may improve their FER abilities. This study contributes to our understanding of the nuanced relationship between cognitive dysfunction and FER in patients with PD-MCI, emphasizing the need for targeted interventions.
Adaptation of a sleep hygiene intervention for individuals with poor sleep and their companions: Results of a randomized controlled pilot trial
Authors: Mindlis Irina , Millar Brett M , Chkhaidze Ana , Fernández Sedano Brandon , Noel Jovanka , Revenson Tracey A
Published: October 2024

Sleep is a major health issue for young adults. While sleep hygiene interventions have small-to-moderate effects, better outcomes might be achieved by delivering interventions individually to those reporting sleep difficulties, or in the presence of a supportive other or companion. To examine the feasibility, acceptability, and initial effects of an adapted sleep hygiene intervention for young adults with poor sleep, we conducted an ORBIT Phase IIb pilot randomized controlled trial (n = 51). Young adults with poor sleep were randomized to receive a sleep hygiene intervention individually or with a companion. Sleep patterns were measured at baseline and 4 weeks. Participants completed daily dairies and wore wearable devices for the month following the intervention. Attrition at follow-up was minimal (3.9%), and missing rates were low for diary data (8%), and in line with prior studies for wearable devices (14%). Participants expressed high levels of satisfaction with the study, with no differences between study arms. Significant effects were found postintervention for all participants, indicating improved sleep quality (t = 6.14, P < .001), greater sleep duration (t = 3.8, P < .001), and reduced daytime sleepiness (t = 2.13, P = .039). There were no significant differences in sleep efficiency pre and postintervention, or between study arms for any sleep outcome based on self-reported and objective data. Results from this pilot provide evidence for the feasibility and acceptability of a sleep hygiene intervention for young adults and lay the groundwork for a larger, fully powered study.
Investigating the existence of an osmotic barrier between xylem fibers and vessels in sugar maple (Acer saccharum) using microCT
Authors: Robinson James A , Rennie Matt , Clearwater Mike J , Holland Daniel J , van den Berg Abby , Watson Matthew J
Published: October 2024

Sugar maples (Acer saccharum Marshall) develop elevated stem pressures in springtime through the compression and expansion of gas bubbles present within xylem fibers. The stability of this gas within the fibers is hypothesized to be due to the elevated sugar concentration of maple sap and the presence of an osmotic barrier between fibers and vessels. Without this osmotic barrier, gas bubbles are predicted to dissolve rapidly. In this work, we investigated the existence of this osmotic barrier. We quantified the fraction of the xylem occupied by gas-filled fibers using synchrotron-based microCT. After imaging fresh stem segments, we perfused them with either a 2% sucrose solution or water, imaging again following perfusion. In this way we directly observed how total gas present in the fibers changed when an osmotic pressure difference should be present, with the 2% sucrose solution, and when it is absent, with the water. Following a first round of perfusion, we perfused stem segments with the other perfusate, repeating this multiple times to observe how switching perfusates affected gas-filled fibers. We found that perfusing stem segments with water resulted in a significant reduction in the xylem fiber gas, but perfusing stem segments with a sucrose solution did not significantly reduce the gas in the fibers. These results support the hypothesis that an osmotic barrier exists between fibers and vessels.
Photosynthetic temperature responses in leaves and canopies: why temperature optima may disagree at different scales
Authors: Kumarathunge Dushan P , Medlyn Belinda E , Drake John E , De Kauwe Martin G , Tjoelker Mark G , Aspinwall Michael J , Barton Craig V M , Campany Courtney E , Crous Kristine Y , Yang Jinyan , Jiang Mingkai
Published: October 2024

Understanding how canopy-scale photosynthesis responds to temperature is of paramount importance for realistic prediction of the likely impact of climate change on forest growth. The effects of temperature on leaf-scale photosynthesis have been extensively documented but data demonstrating the temperature response of canopy-scale photosynthesis are relatively rare, and the mechanisms that determine the response are not well quantified. Here, we compared leaf- and canopy-scale photosynthesis responses to temperature measured in a whole-tree chamber experiment and tested mechanisms that could explain the difference between leaf and crown scale temperature optima for photosynthesis. We hypothesized that (i) there is a large contribution of non-light saturated leaves to total crown photosynthesis, (ii) photosynthetic component processes vary vertically through the canopy following the gradient in incident light and (iii) seasonal temperature acclimation of photosynthetic biochemistry has a significant role in determining the overall temperature response of canopy photosynthesis. We tested these hypotheses using three models of canopy radiation interception and photosynthesis parameterized with leaf-level physiological data and estimates of canopy leaf area. Our results identified the influence of non-light saturated leaves as a key determinant of the lower temperature optimum of canopy photosynthesis, which reduced the temperature optimum of canopy photosynthesis by 6–8 °C compared with the leaf scale. Further, we demonstrate the importance of accounting for within-canopy variation and seasonal temperature acclimation of photosynthetic biochemistry in determining the magnitude of canopy photosynthesis. Overall, our study identifies key processes that need to be incorporated in terrestrial biosphere models to accurately predict temperature responses of whole-tree photosynthesis.
Long-read transcriptomics of Ostreid herpesvirus 1 uncovers a conserved expression strategy for the capsid maturation module and pinpoints a mechanism for evasion of the ADAR-based antiviral defence
Authors: Rosani Umberto , Bortoletto Enrico , Zhang Xiang , Huang Bo-Wen , Xin Lu-Sheng , Krupovic Mart , Bai Chang-Ming
Published: October 2024

Ostreid herpesvirus 1 (OsHV-1), a member of the family Malacoherpesviridae (order Herpesvirales), is a major pathogen of bivalves. However, the molecular details of the malacoherpesvirus infection cycle and its overall similarity to the replication of mammalian herpesviruses (family Orthoherpesviridae) remain obscure. Here, to gain insights into the OsHV-1 biology, we performed long-read sequencing of infected blood clams, Anadara broughtonii, which yielded over one million OsHV-1 long reads. These data enabled the annotation of the viral genome with 78 gene units and 274 transcripts, of which 67 were polycistronic mRNAs, 35 ncRNAs, and 20 natural antisense transcripts (NATs). Transcriptomics and proteomics data indicate preferential transcription and independent translation of the capsid scaffold protein as an OsHV-1 capsid maturation protease isoform. The conservation of this transcriptional architecture across Herpesvirales likely indicates its functional importance and ancient origin. Moreover, we traced RNA editing events using short-read sequencing and supported the presence of inosine nucleotides in native OsHV-1 RNA, consistent with the activity of adenosine deaminase acting on dsRNA 1 (ADAR1). Our data suggest that, whereas RNA hyper-editing is concentrated in specific regions of the OsHV-1 genome, single-nucleotide editing is more dispersed along the OsHV-1 transcripts. In conclusion, we reveal the existence of conserved pan-Herpesvirales transcriptomic architecture of the capsid maturation module and uncover a transcription-based viral counter defence mechanism, which presumably facilitates the evasion of the host ADAR antiviral system.
Increasing the Knee Arc of Motion in Patients With Arthrogryposis: Minimum 2-year Follow-up
Authors: Huser Aaron J. , Brown Michael W. , Nugraha Hans K. , Feldman David S.
Published: October 2024

Background:

Surgery for knee flexion contractures in patients with arthrogryposis multiplex congenital (AMC) have achieved extension to redirect the arc of motion and improve ambulation but has not demonstrated maintained increases in total range of motion (ROM). This study aimed to review the clinical outcomes of combined posterior knee release, proximal femoral shortening, and nerve decompression in patients with arthrogryposis.

Methods:

A retrospective chart and radiographic review were performed on patients with AMC who underwent treatment for knee flexion deformities ≥30 degrees. ROM, ambulation status, and orthotic use were reviewed and analyzed. Complications were recorded.

Results:

Twenty-nine patients with 51 knees and a mean age of 5.7 years were included. The mean follow-up was 36.9 months. The mean ROM increased from 49 to 80 degrees between pre-op and latest follow-up (P<0.0001). The mean final follow-up flexion deformity was 10 degrees (P<0.0001). Preoperative ROM was moderately correlated with final ROM (rs=0.51). The percentage of ambulatory patients improved from 39% to 93%. Five limbs experienced a fracture either intraoperatively or postoperatively, and 5 limbs required a return trip to the operating room.

Conclusions:

Improved ambulation and knee ROM can be maintained in patients with AMC at a minimum 2-year follow-up. Prospective investigation and longer follow-up are required to validate these findings.

Level of Evidence:

Level IV—therapeutic.
Assessment of Adolescent and Parent Willingness to Participate in a Comparative Study of Scoliosis Braces
Authors: Morgan Sara J. , Brown Zelphia C. , Ahmed Mohamed M. , Bauer Jennifer M. , Murphy Joshua S. , Roye Benjamin D. , Truong Walter H.
Published: October 2024

Objective:

Adolescents with idiopathic scoliosis (IS) are often prescribed an orthosis to prevent curve progression and avoid surgery. Standard-of-care scoliosis orthoses are designed for full-time (FT) wear, which can be burdensome for some patients. Nighttime (NT) hypercorrective scoliosis orthoses are another option that has a lower impact on daily life, however, additional research is needed to guide the prescription of NT orthoses. The aim of this study was to assess the willingness of patients with IS and their parents/guardians to enroll in a randomized controlled study on bracing in scoliosis.

Methods:

A cross-sectional study was conducted to survey adolescents with IS and their parents/guardians. Eligibility criteria for adolescent participants included: (1) diagnosis of IS, (2) no previous orthosis use, (3) currently seeing a provider for their scoliosis, and (4) able to communicate in English. Parent/guardian participants were the parent or guardian of an adolescent participant and were able to communicate in English. Separate online surveys were designed for adolescents and their parents/guardians. Surveys provided information about a hypothetical study and queried respondents about whether they would participate in the study, their willingness to randomize brace treatment, and their preferences for NT or FT bracing. Descriptive statistics were used to summarize survey data.

Results:

One hundred four adolescent/parent dyads completed the survey (104 adolescents and 103 parents). Most participants (adolescents: 55.8%, parents: 55.3%) indicated an interest in study participation, and approximately one-third of participants (adolescents: 31.8%, parents: 30.1%) reported that they would be willing to randomize to brace type. Most participants (adolescent: 77.0%, parent: 81.6%) preferred the NT brace if they needed brace treatment.

Conclusions:

High-quality evidence is needed to inform the use of FT and NT scoliosis orthoses. Approximately a third of respondents would enroll in a randomized trial, indicating that multiple collaborative sites will be needed to recruit a sufficient sample into a randomized study on scoliosis bracing. Study findings also demonstrate support from adolescents and their parents/guardians for research on scoliosis bracing.
Perioperative Management of Tibial Spine Fractures in Pediatric Patients: A Delphi Study to Identify Principles of Treatment
Authors: Brenner Madison , Johnson Benjamin , Shea Kevin , Ganley Theodore , Wilson Philip L. ,   PRiSM Tibial Spine Research Interest Group; SCORE Quality Improvement Registry, Ellis Henry B.
Published: October 2024

Background:

The Delphi technique is a structured, iterative group survey method utilized to reach a consensus among experts in a field regarding topics with evidence-based equipoise. Currently, there are few studies at the highest levels of evidence published on the perioperative tibial spine management, making it an ideal subject to utilize expert opinion to reach consensus decision.

Hypothesis/Purpose:

The purpose of this study was to utilize a Delphi-method survey to achieve consensus statements regarding the perioperative management of tibial spine fractures.

Methods:

Before study initiation, 3 rounds of surveys were agreed upon, maintaining the traditional Delphi principles. Consensus was defined as 75% agreement or disagreement on a Likert scale. An anonymous survey consisting of 50 statements describing the management of tibial spine fractures preoperative and postoperative in varying scenarios was distributed to a group of 44 pediatric sports medicine orthopaedic surgeons utilizing an electronic survey software system.

Results:

Of 44 surgeons invited to participate, 24 responded to round 1, 28 responded to round 2, and 25 responded to round 3. Consensus was achieved for the following: use of x-ray to determine initial treatment; casting for a minimum of 3 weeks for nonoperative management, but <3 weeks if treated with surgical fixation; advanced imaging to avoid missing concomitant injury; the necessity of physical therapy, but not continuous passive motion (CPM); and for arthroscopic surgical intervention. It was also agreed that functional testing is important in return-to-play (RTP) decision-making, though the specific timelines and clearance criteria could not be agreed upon. There were statements that displayed continued disagreement, including the role of aspiration, preoperative range of motion management, and the timing of surgical scheduling.

Conclusions:

Utilizing a Delphi methodology with experienced surgeons on tibial spine treatment, consensus in the management of tibial spine fracture was achieved for definitive management strategies. Further study will be important to optimize our management of this youthful population with tibial spine fractures.
Prostate Brachytherapy With Cs-131
Authors: Smith Ryan P. , Mohammed Mohammed A. , Beriwal Sushil , Benoit Ronald M.
Published: October 2024

Objective:

We sought to compare our results of patients treated with Cs-131 prostate brachytherapy (PB) as monotherapy to recently published results of patients treated with stereotactic body radiotherapy.

Methods:

We analyzed data from patients treated at our institution with Cs-131 PB as monotherapy who had at least 5 years of follow-up and who prospectively completed expanded prostate cancer index composite questionnaires at baseline, 1 year, 2 years, and 5 years. We compared our data with the recently published data from radiation therapy oncology group (RTOG) 0938 and PACE-B (NCT01584258).

Results:

A total of 138 patients were included in our cohort. Using RTOG 0938’s definition, the frequency of a decline in urinary function in our PB cohort was 43% compared with 41.3% in RTOG 0938. According to PACE-B’s definition, our PB cohort had minimal clinically important differences in the urinary incontinence domain of 26.4% and in the urinary obstructive/irritative domain of 40.7% at 2 years compared with PACE-B’s reported rate of 32% and 33%, respectively. The frequency of a >5-point change in the expanded prostate cancer index composite bowel summary score at 5 years was 25% compared with 30.7% in RTOG 0938. Our bowel difference at 2 years was 23% compared with PACE-B’s reported 24%. Our 5-year biochemical disease free survival (bDFS) was 97.8%, compared with 91.3% in RTOG 0938 and 95.8% in PACE-B.

Conclusions:

Low dose rate (LDR) PB with Cs-131 as monotherapy provides excellent biochemical control of prostate cancer in low and intermediate-risk patients. Our cohort of patients had modest differences in patient-reported urinary and bowel quality of life compared with baseline. These differences were comparable to recently published stereotactic body radiotherapy data. When comparing prostate cancer treatments in terms of patient convenience and available resources, PB certainly should be considered.
Comparative study of labour analgesia onset with injection of loading dose through epidural needle versus catheter
Authors: Chen XiaoPing , Tang YingYing , Yu QingQing , Sun LiHong , Li Hua , Wang LuYang , Jiao Cuicui , Chen XinZhong
Published: October 2024

BACKGROUND

Rapid onset of epidural analgesia is an important concern for the parturient. Commonly, the local anaesthetic mixture is administered through the epidural catheter. Drugs administered through the epidural needle might decrease the onset time and enhance the spread of medication within the epidural space.

OBJECTIVES

The primary aim of this study was to compare the onset time of analgesia when a loading dose of dilute local anaesthetic opioid mixture was injected through either the Tuohy needle or a single end-hole epidural catheter.

DESIGN

A prospective, double-blinded, randomised clinical trial.

SETTING

Single university hospital, from November 2022 to August 2023.

PARTICIPANTS

A total of 200 healthy nulliparous women who requested epidural analgesia for labour were randomly allocated to the needle group (n = 100) or the catheter group (n = 100).

INTERVENTIONS

In the needle group, after identification of the epidural space, a test dose of 3 ml 0.1% ropivacaine with 0.3 μg ml−1 sufentanil was injected through the Tuohy needle followed 3 min later by a 15 ml loading dose of the same mixture over 30 s. Then the catheter was inserted into the epidural space. In the catheter group, after identification of the epidural space, a catheter was advanced into the epidural space and the ropivacaine/sufentanil mixture was injected in an identical manner though the catheter.

MAIN OUTCOME MEARSURES

The primary outcome was the onset time of labour analgesia (defined as the time from drug administration to adequate analgesia). Adequate analgesia was defined as a visual analogue score 10 mm or less during uterine contractions.

RESULTS

Median [IQR] onset time of labour analgesia did not differ significantly between the two groups (needle group: 20 [16 to 30] minutes; catheter group: 20 [15 to 25] minutes, P = 0.232).

CONCLUSION

Compared with bolus injection though a single end-hole epidural catheter, injection through the epidural needle did not shorten the analgesia onset time for adequate labour analgesia.

TRIAL REGISTRATION

ClinicalTrials.gov (NCT05594771).
Neighborhood-level deprivation mediates racial and ethnic disparities in HCC diagnosis in Texas
Authors: Sokale Itunu O. , Thrift Aaron P. , El-Serag Hashem B. , Oluyomi Abiodun O.
Published: October 2024

Background:

Texas has the highest HCC rates in the United States, and the greatest burden is among Hispanics. Racial and ethnic disparities in HCC incidence have multiple underpinning factors. We conducted a mediation analysis to examine the role of neighborhood disadvantage (Area Deprivation Index) as a potential mediator of the association between neighborhood race and ethnicity distribution and neighborhood HCC case counts in Texas.

Methods:

The primary outcome measure was counts of new HCC diagnoses per census tract based on Texas Department of State Health Services Texas Cancer Registry data. The primary exposure of interest was the race and ethnicity-based Index of Concentration at the Extremes (non-Hispanic Black ICE or Hispanic ICE). We assessed Area Deprivation Index as a potential mediator of the association between Black/Hispanic ICE and HCC case counts. We adjusted the analyses for selected census tract characteristics.

Results:

We analyzed 4934 census tracts containing 13,632 new HCC diagnoses reported to Texas Cancer Registry between 2016 and 2020. Racial minority (Black/Hispanic ICE)-concentrated neighborhoods had a higher socioeconomic disadvantage. The results of the mediation analyses showed that compared to non-Hispanic White–concentrated census tracts, non-Hispanic Black–concentrated census tracts and Hispanic-concentrated census tracts had higher case counts of HCC (total effects: adjusted case count ratio: 1.03 [95% CI, 1.02–1.04] and adjusted case count ratio: 1.09 [95% CI, 1.08–1.10], respectively). Approximately 48% and 15% of the neighborhood-level disparity in HCC case counts were attributable to neighborhood socioeconomic disadvantage in Black and Hispanic minoritized neighborhoods, respectively.

Conclusions:

Neighborhood HCC case counts varied by neighborhood race and ethnicity distribution. The variations were partly explained by neighborhood deprivation, with a stronger effect among Black-concentrated census tracts.
Association of gut microbiota and gut metabolites and adverse outcomes in biliary atresia: A longitudinal prospective study
Authors: Jain Vandana , Dalby Matthew J. , Alexander Emma C. , Burford Charlotte , Acford-Palmer Holly , Serghiou Iliana R. , Teng Nancy M.Y. , Kiu Raymond , Gerasimidis Konstantinos , Zafeiropoulou Konstantina , Logan Michael , Verma Anita , Davenport Mark , Hall Lindsay J. , Dhawan Anil
Published: October 2024

Background:

The Kasai portoenterostomy (KPE) aims to re-establish bile flow in biliary atresia (BA); however, BA remains the commonest indication for liver transplantation in pediatrics. Gut microbiota-host interplay is increasingly associated with outcomes in chronic liver disease. This study characterized fecal microbiota and fatty acid metabolites in BA.

Methods:

Fecal samples were prospectively collected in newly diagnosed BA infants (n = 55) before and after KPE. Age-matched healthy control (n = 19) and cholestatic control (n = 21) fecal samples were collected. Fecal 16S rRNA gene amplicon sequencing for gut microbiota and gas chromatography for fecal fatty acids was performed.

Results:

Increased abundance of Enterococcus in pre-KPE BA and cholestatic control infants, compared to healthy infants, was demonstrated. At the early post-KPE time points, increased alpha diversity was revealed in BA versus healthy cohorts. A lower relative abundance of Bifidobacterium and increased Enterococcus, Clostridium, Fusobacterium, and Pseudomonas was seen in infants with BA. Fecal acetate was reduced, and fecal butyrate and propionate were elevated in early post-KPE BA infants. Higher post-KPE alpha diversity was associated with nonfavorable clinical outcomes (6-month jaundice and liver transplantation). A higher relative abundance of post-KPE Streptococcus and Fusobacterium and a lower relative abundance of Dorea, Blautia, and Oscillospira were associated with nonfavorable clinical outcomes. Blautia inversely correlated to liver disease severity, and Bifidobacterium inversely correlated to fibrosis biomarkers. Bifidobacterium abundance was significantly lower in infants experiencing cholangitis within 6 months after KPE.

Conclusions:

Increased diversity, enrichment of pathogenic, and depletion of beneficial microbiota early post-KPE are all factors associated with nonfavorable BA outcomes. Manipulation of gut microbiota in the early postsurgical period could provide therapeutic potential.