bluuebunny/crossref_metadata_2025 huggingface dataset:
RBIO-02. ACTIVATION OF GABAA RECEPTORS WITH A NON-TOXIC, BRAIN PENETRANT SMALL MOLECULE SENSITIZES LUNG ADENOCARCINOMA PRIMARY AND BRAIN METASTATIC TUMOR CELLS TO RADIATION VIA AUTOPHAGY INDUCTION
Authors: Bhattacharya Debanjan , Barille Riccardo , Toukam Donatien Kamdem , Gawali Vaibhavkumar , Kallay Laura , Ahmed Taukir , Cook James , Karve Aniruddha , Desai Pankaj , Medvedovic Mario , Krummel Daniel Pomeranz , Sengupta Soma
Published: November 2022

Most advanced-stage non-small cell lung cancer (NSCLC) patients have brain metastases that render a dismal prognosis. Treatment of metastatic brain lesions from NSCLC and other tumor types include radiation as part of a multimodal treatment regimen. Challenges in the application of radiotherapy include overcoming radiation resistance and reducing associated co-morbidities. Non-toxic therapeutics capable of sensitizing tumors to radiation are needed to improve survival and mitigate radiation side-effects. Many CNS and solid systemic tumors express ligand-gated ion channels, which may contribute to tumor growth. Leveraging ion channels is therefore a potential way of diminishing the spread of cancer. We find that NSCLC and its brain metastases express subunits of the type-A GABA-gated chloride channel or GABAA receptor. Importantly, patient-derived NSCLC cells have functional GABAA receptors. We identified a brain penetrant, small molecule activator of GABAA receptors (AMLAL-101), which alone impairs the viability of both primary NSCLC cells and brain metastatic cells. In addition, AMLAL-101 combined with radiation is a highly potent inducer of NSCLC cell death and clonogenic arrest. Using a human ex vivo model of NSCLC-on-chip, we assessed the efficacy and toxicity of AMLAL-101 relative to Docetaxel, an antimicrotubular agent used in treating advanced NSCLC. AMLAL-101 is as potent as Docetaxel but does not exhibit its toxic side effects. AMLAL-101 also potentiates radiation in vivo, significantly reducing lung adenocarcinoma xenograft tumor growth in mice, equivalent to docetaxel plus radiation. Mechanistically, AMLAL-101 activates GABAA receptors in NSCLC and synergizes with radiation by inducing an autophagic response that includes: (i) stabilization of Beclin-1, BNIP3L/NIX, and GABARAP; (ii) ATG7 upregulation; and (iii) utilization of ubiquitin-binding protein p62. Activating GABAA receptors in NSCLC and other tumor types may improve radiation efficacy and mitigate its toxic side effects in treating brain metastases.
RBIO-05. QUANTIFICATION OF TSPO EXPRESSION AND TSPO RADIOLIGAND UPTAKE IN PET IN HUMAN AND MURINE GLIOBLASTOMA ON CELLULAR LEVEL
Authors: Kirchleitner Sabrina , Bartos Laura , Tonn Joerg-Christian , Albert Nathalie , Glass Rainer , Kaelin Roland , Quach Stefanie , Binter Fabian , Holzgreve Adrien , Brendel Matthias
Published: November 2022

OBJECTIVE

Translocator protein (TSPO) PET imaging is used in different neurological diseases and emerges as new tool for the diagnosis and therapy planning of glioma patients. Various signal sources of the TSPO-PET signal, however, hamper image interpretation and biological understanding. Here we assess the TSPO expression and ligand uptake in a murine model and human tissue derived from glioma patients.

METHODS

Mice with implanted GFP+ glioblastoma (n=20) or after sham implantation (n=14) were injected with the TSPO tracer [18F]GE-180 and received PET imaging. Tumors were harvested and processed to single cell suspension. Subsequently, tumors were either stained for TSPO, CD11b, ACSA2, GFAP and analyzed by flowcytometry or else magnetic cell sorting was performed to isolate tumor and CD11b+ cells that were measured by gamma counter. Multiple regression was used to determine contributions of GFP, CD11b, ACSA2 and GFAP positive cells to the total uptake. In TSPO PET-scans of glioma patients, regions with different GE-180 uptake were defined. Tumor samples (n=12) of these predefined areas were collected during surgery and analyzed by FACS as described above.

RESULTS

The expression of TSPO and PET signal in mice was increased in the tumor compared to tumor-free brain (SUVRGBM: 2.06 / SUVRSHAM: 0.92). FACS detected TSPO in tumor cells, microglia/macrophages and astrocytes. Tumor cells showed higher tracer uptake per cell when compared to CD11b+ cells (+31%). The contribution to the whole TSPO tracer uptake was high for tumor (β=0.41, P=0.018) and microglia/macrophages (β=0.35, P=0.042), and lowest for astrocytes (β=0.28, P=0.011). Patients with high-grade glioma indicated higher TSPO tracer uptake in GFAP+ cells when compared to CD11b+ cells and single cell uptake correlated with PET signal.

CONCLUSION

In experimental orthotopic glioblastoma, we could detect TSPO tracer signal at cellular resolution level. TSPO-PET can provide information about tumor and tumor-associated myeloid cells.
RBIO-06. CLINICAL AND MOLECULAR PREDICTORS OF RADIATION RESPONSIVENESS IN MENINGIOMAS: A MULTICENTER RETROSPECTIVE COHORT STUDY
Authors: Wang Justin , Nassiri Farshad , Patil Vikas , Liu Jeff , Lee Grace , Rogers Lauren , Tsang Derek , Laperriere Normand , Zadeh Gelareh
Published: November 2022

BACKGROUND

Aside from surgery, radiotherapy (RT) remains the only standard of care treatment for meningiomas. However, few studies have identified clinical/molecular biomarkers associated with responsiveness to RT and the optimal timing of RT after surgery remains controversial. We aimed to assess outcomes in a large multi-institutional cohort of RT-treated meningiomas to identify clinical factors and DNA methylation and RNA expression markers associated with progression-free survival (PFS) post-RT.

METHODS

Patients with intracranial meningiomas who underwent treatment with fractionated RT between 1997-2018 were included. DNA-methylation using the Illumina 850K EPICArray and RNA-sequencing were performed on tumours with sufficient tissue. Primary endpoints were radiographic recurrence of progression and time to progression from the time of RT completion.

RESULTS

404 meningiomas were included for analysis. Of these, 167 (41.3%) recurred post-RT, usually within 5-years of RT. Previous RT to the meningioma, having a WHO grade 3 meningioma, and older age at diagnosis were independently associated with poorer PFS post-RT. Following propensity score matching, patients that received adjuvant RT had significantly better PFS post-RT compared to those that received salvage RT after recurrence (p=0.04). DNA methylation on 220 of these meningiomas segregated tumours into two distinct methylation groups (RT-resistant and RT-sensitive) based on unsupervised consensus clustering. DNA methylation were able to independently predict PFS post-RT better than all clinical factors. Differential RNA-expression analysis of these groups showed up-regulation of pathways involved in chromosome segregation and mitotic cell cycle and down-regulation of fatty acid metabolism pathways in RT-resistant meningiomas.

CONCLUSION

While there are a paucity of clinical factors that can reliably predict a meningioma’s response to RT, DNA methylation and RNA expression biomarkers may aid in differentiating RT-resistant meningiomas from RT-sensitive tumours. Patients that receive adjuvant RT may have prolonged PFS post-RT compared to those that receive salvage RT only after recurrence has already occurred.
RBIO-08. MEMANTINE INCREASES DENDRITIC ARBORIZATION OF IMMATURE NEURONS AFTER IRRADIATION WITH NO EVIDENCE OF DISRUPTION IN THE NORMAL BRAIN FUNCTION
Authors: Zisiadis Georgios Alkis , Rodrigues Carlos , Pizzirusso Giussy , Arroyo-García Luis , Osman Ahmed , Blomgren Klas
Published: November 2022

Cranial irradiation (IR) is a cornerstone in the treatment of high-grade pediatric brain tumors. While lifesaving, it is associated with severe sequalae in 50-90 % of the survivors, as they often show disabling cognitive dysfunction, declined IQ, impaired processing speed, anxiety and posttraumatic stress symptoms, resulting in poorer academic accomplishments and social isolation. Memantine (Mem) is a non-competitive NMDA receptor antagonist and a potent enhancer of neural plasticity. While an improvement in cognition in post-IR cancer survivors and in synaptic plasticity in association to hippocampal neurogenesis have been documented, the exact mechanisms underlying Mem’s actions are poorly understood. The goal of this project is to further dissect the actions of Mem and identify factors that contribute to hippocampal neurogenesis. To this end, 20-day-old C57BL6/J mice were subjected to a single dose of 7 Gy whole brain irradiation and then supplied with Mem in the drinking water (10 mg/kg/day) to obtain a steady-state plasma concentration of the drug. Two weeks after IR, Sholl analysis of the morphology of the newborn neurons of Mem treated animals showed a statistically significant increase in coverage area (500 µm2 vs. 250 µm2, p < 0,0001) and number of dendrites (15 vs. 5, p < 0,0001) compared to non-treated individuals. Bulk-RNA sequencing analysis revealed 9 differentially expressed genes (alpha=0.1) between the hippocampal cell populations of Mem and vehicle-treated IR mice, which are related to protein folding and the programmed cell death machinery. At six weeks after IR, Mem treatment maintains the gamma oscillatory dynamics in the hippocampal CA3 region (~2x10-9 V2 in non-IR, ~1x109 V2 in IR), but with no apparent recovery to the sham levels. These results emphasize the strong neurogenic effect that Mem exerts on the surviving newborn neurons, while also highlighting Mem’s low toxicity and impact on the normal function of the brain.
RTID-04. CLINICAL POTENTIAL OF TARGETING TRANSFORMING GROWTH FACTOR BETA 2 WITH OT-101 FOR POST-RADIATION CONSOLIDATION IN DIFFUSE INTRINSIC PONTINE GLIOMA
Authors: Uckun Fatih , Trieu Vuong
Published: November 2022

Diffuse intrinsic pontine glioma (DIPG) in children has a dismal prognosis with a median overall survival (OS) of 10 months and a 2-year overall survival rate of < 10% after standard radiation therapy. Chemotherapy does offer clinically meaningful benefits. Therefore, there is an urgent need for therapeutic innovations for treatment of pediatric DIPG. High-grade glioma cells, including pediatric glioblastoma and DIPG cells have been shown to produce transforming growth factor beta 2 (TGFB2) which has been implicated both as promoter of glioma cells and as a key contributor to the T-cell hyporesponsiveness of the tumor microenvironment (TME) towards glioma cells. OT-101 is a first-in-class RNA therapeutic designed to abrogate the immunosuppressive and tumor promoting actions of TGF-B2. At low micromolar concentrations, OT-101 reduces the TGFB2 secretion by human glioma cells, blocks their proliferation as well as migration, and restores the anti-glioma cytolytic function of patient-derived T-cells. In a Phase 2 clinical study, intracerebrally applied OT-101 administered via convection-enhanced delivery showed promising single agent activity in Recurrent/Refractory (R/R) high-grade glioma (HGG) (Uckun et al., Cancers. 2019 28;11(12):1892). The intrathecal administration of antineoplastic drugs directly in the CSF allows to bypass the selective filter of BBB, achieving significant concentrations of the antineoplastic agents in CSF, while reducing the likelihood of systemic toxicity. Informed by favorable safety pharmacology studies of intrathecally delivered OT-101 in rabbits and primates and encouraged by its single agent activity in adult patients with HGG, we decided to embark upon a multi-center, two-part, randomized Phase 1-2 study of OT-101 in pediatric patients with DIPG. Multiple doses of OT-101 will be administered after completion of radiation therapy as intrathecal bolus injections. The study is designed to determine: 1) the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of OT-101, and 2) its efficacy in children with DIPG.
SURG-11. AKT1 E17K AND NF2 MUTATIONS DOMINATE SPINAL MENINGIOMAS WHO GRADE 1 AND PRESENT DISTINCT TUMOR FEATURES
Authors: Hua Lingyang , Alkhatib Majd , Meinhardt Matthias , Cahill Daniel , Brastianos Priscilla , Clark Victoria , Shankar Ganesh , Wakimoto Hiroaki , Schackert Gabriele , Juratli Tareq
Published: November 2022

INTRODUCTION

While the mutational landscape of intracranial meningiomas has been extensively studied, our understanding of the molecular profile of spinal meningiomas (SM) remains incomplete. In this study, we correlate the molecular status with tumor features in a clinically well-characterized cohort.

METHODS

Samples from 50 patients (38 females and 12 males) with WHO grade 1 SM were collected. We performed next-generation sequencing (NGS) using an assay covering frequently mutated genes in meningiomas including AKT1, KLF4, NF2, PIK3CA, POLR2A, SMARCB1, SMARCE1, SMO, SUFU, and TRAF7. We correlated clinical and imaging data with the molecular tumor status.

RESULTS

AKT1 E17K mutations were detected in 15 (30%) and NF2 mutations in 32 (64%) patients. Both mutations were mutually exclusive. In contrast to AKT1-mutant intracranial meningiomas, AKT1-mutant SM only harbored a TRAF7 co-mutation in a single case. NF2-mutant meningiomas had a significant female predominance (n= 30/32, 94%) when compared to the balanced incidence of AKT1-mutant tumors (n= 7/15, 46.7%, p= 0.0006). The two groups demonstrated stark differences in the location: a thoracic localization was significantly more common in NF2-mutant meningiomas (n= 25/32, 78.1%, p= 0.0012), while meningiomas harboring an AKT1 mutation were predominantly located in the cervical spine (n= 11/15, 73.3%). Moreover, while a substantial proportion of NF2-mutant meningiomas developed in the dorsal location (n= 19/32, 59.3%), the vast majority of AKT1-mutant meningiomas (n= 13/15, 87%) arose ventral to the spinal cord. The histologic subtype of NF2-mutant meningiomas was variable, while all but one AKT1-mutant meningioma showed meningothelial histology (93.3%, p= 0.0001). All calcified meningiomas (n= 17) were NF2-mutant (p= 0.0002), whereas none of the AKT1-mutant meningiomas showed intratumoral calcifications.

CONCLUSIONS

Our findings support the central role of AKT1 and NF2 mutations in the molecular pathogenesis of WHO grade 1 SM. These mutations are mutually exclusive and are associated with distinct tumor and clinical features.
SURG-27. THERAPEUTIC OPTIONS FOR RECURRENT GLIOBLASTOMA-EFFICACY AND SAFETY OF TALAPORFIN SODIUM MEDIATED PHOTODYNAMIC THERAPY WITH MAXIMAL RESECTION
Authors: Muragaki Yoshihiro , Kobayashi Tatsuya , NItta Masayuki , Shimizu Kazuhide , Kawamata Takakazu
Published: November 2022

INTRODUCTION

Recurrent glioblastoma (GBM) remains one of the most challenging clinical issues, with no standard treatment and effective treatment options.

METHODS

To evaluate the efficacy of talaporfin sodium (TS) mediated photodynamic therapy (PDT) as a new treatment for this condition, we retrospectively analyzed 70 patients who underwent surgery of maximal resection with PDT (PDT group) for recurrent GBM and 38 patients who underwent surgery of maximal resection alone (control group).

RESULTS

The median progression-free survival (PFS) in the PDT and control groups after second surgery was 5.7 and 2.2 months, respectively (p = 0.0043). The median overall survival (OS) after the second surgery was 16.0 and 12.8 months, respectively (p = 0.031). Both univariate and multivariate analyses indicated that surgery with PDT and a preoperative Karnofsky Performance Scale were significant independent prognostic factors for PFS and OS. In the PDT group, there was no significant difference regarding PFS and OS between patients whose previous pathology before recurrence was already GBM and those who had malignant transformation to GBM from lower grade glioma. PDT was well tolerated by all patients and in no case did treatment-related severe adverse effects. There was also no significant difference in TS accumulation in the tumor between these two groups.

CONCLUSION

According to these results, additional PDT treatment for recurrent GBM could have potential survival benefits and its efficacy is independent of the pre-recurrence pathology.
Comparison of Indirect Fungal Diagnostic Tests in Patients With Proven Histoplasmosis
Authors: Krishnan Gayathri , Power Margaret , Bariola J Ryan , Dare Ryan
Published: November 2022

Background

Histoplasmosis is a common cause of invasive fungal infection in endemic regions and accurate diagnosis is difficult without direct tissue culture or pathology. Indirect fungal antigen testing for various fungal pathogens are typically performed to assist with diagnostic workup, though cross-reaction can lead to difficulty in interpreting results. We aimed to compare indirect fungal diagnostic tests and evaluate prevalence of positive antigen testing for non-Histoplasma fungal pathogens in patients with proven histoplasmosis.

Methods

We performed a single-center retrospective review of adult patients with proven histoplasmosis diagnosed by fungal culture and/or cytology from January 2010 to March 2018. Patient demographics, clinical characteristics, and results of fungal antigen testing for Histoplasma, Blastomyces, Aspergillus, Cryptococcus, and (1→3)-β-D-glucan were evaluated. Two different urine Histoplasma antigen assays were used during the study period.

Results

Fifty-seven of 182 (31.3%) patients reviewed had proven histoplasmosis and presented with acute pulmonary (n = 10), chronic pulmonary (n = 7), and disseminated (n = 40) disease. Forty-one (72%) of these patients were immunosuppressed. Urine Blastomyces antigen (93%) and serum (1→3)-β-D-glucan (88%) were commonly positive in patients with histoplasmosis, whereas Aspergillus antigen was detected in 50% of patients and Cryptococcus antigenemia was rare (5%). In patients with disseminated disease, the MiraVista urine Histoplasma antigen assay had higher sensitivity than the Viracor urine Histoplasma antigen assay (86% vs 50%, respectively; P = .019).

Conclusions

Noninvasive fungal antigen assays are helpful diagnostic tools; however, given their low specificity, clinicians must be aware of the various clinical presentations of invasive fungal infections and be aware of the limitations of these tests.
Biobehavioral Assessments in BACPAC: Recommendations, Rationale, and Methods
Authors: Greco Carol M , Wasan Ajay D , Schneider Michael J , Mehling Wolf , Williams David A , Darwin Jessa , Harte Steven E
Published: November 2022

The Biobehavioral Working Group of BACPAC was charged to evaluate a range of psychosocial, psychophysical, and behavioral domains relevant to chronic low back pain, and recommend specific assessment tools and procedures to harmonize biobehavioral data collection across the consortium. Primary references and sources for measure selection were the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials, the Minimum Data Set from the National Institutes of Health (NIH) Research Task Force on Standards for Chronic Low Back Pain, the Patient-Reported Outcomes Measurement Information System, and NeuroQOL. The questionnaire’s recommendations supplemented the NIH HEAL Common Data Elements and BACPAC Minimum Data Set. Five domains were identified for inclusion: Pain Characteristics and Qualities; Pain-Related Psychosocial/Behavioral Factors; General Psychosocial Factors; Lifestyle Choices; and Social Determinants of Health/Social Factors. The Working Group identified best practices for required and optional Quantitative Sensory Testing of psychophysical pain processing for use in BACPAC projects.
No Work for Fundamental Facts
Authors: Oberle Thomas
Published: November 2022

Metaphysical foundationalists argue that without fundamental facts, we cannot explain why there exist any dependent facts at all. Thus, metaphysical infinitism, the view that chains of ground can descend indefinitely without ever terminating in a level of fundamental facts, allegedly exhibits a kind of explanatory failure. I examine this argument and conclude that foundationalists have failed to show that infinitism exhibits explanatory failure. I argue that explaining the existence of dependent facts in terms of further dependent facts ad infinitum is unproblematic by arguing for the plausibility of a ground-theoretic version of the Hume-Edwards Principle, which states that if each fact in a plurality of facts has a ground, then the plurality itself has a ground.
Gene amplification acts as a molecular foothold to facilitate cross-species adaptation and evasion of multiple antiviral pathways
Authors: Banerjee Shefali , Smith Cathy , Geballe Adam P , Rothenburg Stefan , Kitzman Jacob O , Brennan Greg
Published: November 2022

Cross-species spillover events are responsible for many of the pandemics in human history including COVID-19; however, the evolutionary mechanisms that enable these events are poorly understood. We have previously modeled this process using a chimeric vaccinia virus expressing the rhesus cytomegalovirus–derived protein kinase R (PKR) antagonist RhTRS1 in place of its native PKR antagonists: E3L and K3L (VACVΔEΔK + RhTRS1). Using this virus, we demonstrated that gene amplification of rhtrs1 occurred early during experimental evolution and was sufficient to fully rescue virus replication in partially resistant African green monkey (AGM) fibroblasts. Notably, this rapid gene amplification also allowed limited virus replication in otherwise completely non-permissive human fibroblasts, suggesting that gene amplification may act as a ‘molecular foothold’ to facilitate viral adaptation to multiple species. In this study, we demonstrate that there are multiple barriers to VACVΔEΔK + RhTRS1 replication in human cells, mediated by both PKR and ribonuclease L (RNase L). We experimentally evolved three AGM-adapted virus populations in human fibroblasts. Each population adapted to human cells bimodally, via an initial 10-fold increase in replication after only two passages followed by a second 10-fold increase in replication by passage 9. Using our Illumina-based pipeline, we found that some single nucleotide polymorphisms (SNPs) which had evolved during the prior AGM adaptation were rapidly lost, while thirteen single-base substitutions and short indels increased over time, including two SNPs unique to human foreskin fibroblast (HFF)–adapted populations. Many of these changes were associated with components of the viral RNA polymerase, although no variant was shared between all three populations. Taken together, our results demonstrate that rhtrs1 amplification was sufficient to increase viral tropism after passage in an ‘intermediate species’ and subsequently enabled the virus to adopt different, species-specific adaptive mechanisms to overcome distinct barriers to viral replication in AGM and human cells.
Successful administration of low-dose almonertinib in a patient with lung adenocarcinoma after osimertinib-induced interstitial lung disease: a case report and literature review
Authors: Chen Wenyan , Zhang Lijuan , Shen Hui , Wang Bin , Luo Jiayou , Cui Enhai
Published: November 2022

Osimertinib, the third generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is the standard treatment for nonsmall cell lung cancer with EGFR mutation. However, osimertinib-induced interstitial lung disease (OsiILD) is considered to be a serious adverse event, so some patients will have to discontinue the use of osimertinib due to OsiILD. Almonertinib is a novel third-generation EGFR-TKI. We herein report a patient who developed OsiILD after the use of osimertinib and then switched to almonertinib for further treatment with success. This is the first report of a successfull rechallenge with low-dose almonertinib after OsiILD. We also reviewed the literature to explore the possible risk factors and the subsequent treatment of OsiILD, suggesting that low-dose almonertinib may be an option for follow-up treatment of OsiILD.
Methamphetamine-induced locomotor sensitization in mice is not associated with deficits in a range of cognitive, affective and social behaviours: interaction with brain-derived neurotrophic factor Val66Met genotype
Authors: Corrone Michelle , Ratnayake Ruvee , de Oliveira Nicole , Jaehne Emily J , van den Buuse Maarten
Published: November 2022

Chronic methamphetamine (Meth) abuse may induce psychosis similar to that observed in schizophrenia. Brain-derived neurotrophic factor (BDNF) has been implicated in the development of psychosis. We have previously shown long-term protein expression changes in mice treated chronically with Meth depending on BDNF Val66Met genotype. The aim of this study was to investigate if these protein expression changes were associated with differential changes in a range of behavioural paradigms for cognition, anxiety, social and other behaviours. Male and female Val/Val, Val/Met and Met/Met mice were treated with an escalating Meth dose protocol from 6 to 9 weeks of age, with controls receiving saline injections. Several overlapping cohorts were tested in the Y-maze for short-term spatial memory, novel-object recognition test, context and cued fear conditioning, sociability and social preference, elevated plus maze for anxiety-like behaviour and prepulse inhibition (PPI) of acoustic startle. Finally, the animals were assessed for spontaneous exploratory locomotor activity and acute Meth-induced locomotor hyperactivity. Acute Meth caused significantly greater locomotor hyperactivity in mice previously treated with the drug than in saline-pretreated controls. Meth-pretreated female mice showed a mild increase in spontaneous locomotor activity. There were no Meth-induced deficits in any of the other behavioural tests. Val/Met mice showed higher overall social investigation time and lower PPI compared with the Val/Val genotype independent of pretreatment. These results show limited long-term effects of chronic Meth on a range of cognitive, affective and social behaviours despite marked drug-induced locomotor sensitization in mice. There was no interaction with BDNF Val66Met genotype.
Changes in Etiology of Invasive Bacterial Infections in Infants Under 3 Months of Age in Korea, 2006–2020
Authors: Song Seung Ha , Lee Hoan Jong , Song Eun Song , Ahn Jong Gyun , Park Su Eun , Lee Taekjin , Cho Hye-Kyung , Lee Jina , Kim Yae-Jean , Jo Dae Sun , Kim Jong-Hyun , Kang Hyun Mi , Lee Joon Kee , Kim Chun Soo , Kim Dong Hyun , Kim Hwang Min , Choi Jae Hong , Eun Byung Wook , Kim Nam Hee , Cho Eun Young , Kim Yun-Kyung , Oh Chi Eun , Kim Kyung-Hyo , Ma Sang Hyuk , Jung Hyun Joo , Lee Kun Song , Kim Kwang Nam , Lee Hyunju , Choi Eun Hwa
Published: November 2022

Objectives:

Invasive bacterial infection (IBI) causes a significant burden in infants. In this study, we analyzed changes in epidemiology of IBI among infants in Korea.

Methods:

A retrospective multicenter-based surveillance for IBIs in infants <3 months of age was performed during 2006–2020. Cases were classified as an early-onset disease (EOD) (0–6 days) or late-onset disease (LOD) (7–89 days). The temporal trend change in proportion of pathogens was analyzed.

Results:

Among 1545 cases, the median age was 28 days (IQR: 12, 53) and EOD accounted for 17.7%. Among pathogens, S. agalactiae (40.4%), E. coli (38.5%), and S. aureus (17.8%) were the most common and attributed for 96.7%. Among EOD (n = 274), S. agalactiae (45.6%), S. aureus (31.4%), E. coli (17.2%) and L. monocytogenes (2.9%) were most common. Among LOD (n = 1274), E. coli (43.1%), S. agalactiae (39.3%), S. aureus (14.9%) and S. pneumoniae (1.3%) were most common. In the trend analysis, the proportion of S. aureus (r s = −0.850, P < 0.01) decreased significantly, while that of S. agalactiae increased (r s = 0.781, P < 0.01).

Conclusion:

During 2006–2020, among IBI in infants <3 months of age, S. agalactiae, E. coli, and S. aureus were most common and an increasing trend of S. agalactiae was observed.
Validation of the Algorithmic Prediction of Failure Modes in Health Care Methodology: Applied to the Department of Sterile Supply and Equipment
Authors: Kobo-Greenhut Ayala , Sharlin Ortal , Fishman Tatyana , Daniel Liron , Frankenthal Hilel , Eisenberg Vered H. , Zimlichman Eyal , Orkin Dina
Published: November 2022

Failure mode and effect analysis (FMEA) is a leading tool for risk management in health care. The term “blanket” approach FMEA describes a comprehensive simultaneous look at the variety of interrelated factors that may directly and indirectly affect patient safety. Applying FMEA with the “blanket” approach is not common, due to FMEA’s limitations. Algorithmic prediction of failure modes in health care (APFMH) is leaner and enables the application of the “blanket” approach, but, like FMEA, it lacks formal validation. The authors set out to validate the APFMH method while applying a “blanket” approach. They analyzed the sterile supply handling at a 1900-bed academic medical center. The study’s first step took place in the operating room (OR) aspect of the process. An APFMH analysis was performed using the “blanket” approach, to identify the hazards and define the common root causes for predicted hazards. The second step took place a year later at the sterile supply and equipment department (SSED) and aimed to validate these root causes, thus validating the reliability of APFMH. The “blanket” approach analysis with the APFMH method consisted of categorization into 3 risk-dimensions: patient safety, equipment damage, and time management. Root causes were defined for 8 high-ranking hazards. All the root causes for failures, identified by APFMH at the OR department, were revealed as actual hazards in the processes of the SSED. The independent findings at the SSED level validated the list of identified hazards that was formed at the target department (ie, the OR). APFMH methodology is a lean in time and human resources process that ensures comprehensive hazard analysis, which can include the “blanket” approach, and which was validated in this study. The authors suggest using the APFMH methodology for any organizational analysis method that requires the inclusion of “blanket” approaches.
Enhancing bladder management for intrapartum/postpartum women at a maternity hospital in Taiwan: a best practice implementation project
Authors: Pan Wan-Lin , Chen Li-Li , Wang Chia-Hui , Mu Pei-Fan , Tsay Shwu-Feng , Gau Meei-Ling
Published: November 2022

Introduction and aims:

Voiding dysfunction is a common perinatal condition. Appropriate bladder management and monitoring during labor and postpartum improves bladder function and reduces the incidence of infections and complications. This project aimed to promote evidence-based bladder management strategies for perinatal women at a maternity hospital in Taiwan.

Methods:

The project was implemented using the JBI framework and the JBI Practical Application of Clinical Evidence System. Implementation audits were conducted by examining nurses and intrapartum and postpartum women. Ten criteria were applied in the baseline audit, and two follow-up audits were conducted to assess actual compliance with best-practice recommendations. Through a Getting Research into Practice analysis, we identified three barriers to changing practice.

Results:

A comparison of the audit outcomes revealed that all criteria had improved by the second follow-up audit cycle. Specifically, the compliance rate increased from 37% and 50% to 100% for criteria 1 and 2, respectively; from 0% to 100% for criteria 3, 5, and 10; and from 7%, 28%, 50%, and 17% to 100%, 100%, 97%, and 100% for criteria 4, 6, 8, and 9, respectively. Following implementation, the frequency of intrapartum intermittent catheterization (53.44–38.30%) and the postpartum incidence of urinary retention (9.09–8.51%) decreased. The time to first voiding after vaginal delivery and between the first and the second voiding decreased from 5.51 and 4.01 h to 2.32 and 2.29 h, respectively.

Conclusions:

This evidence-based implementation project achieved substantial improvements in bladder management. Relational leadership theory, which integrates empowerment, purposefulness, ethical behaviors, and process orientation, underpinned the project.
Invasive alien acacias rapidly stock carbon, but threaten biodiversity recovery in young second-growth forests
Authors: Matos Fabio A. R. , Edwards David P. , S. Magnago Luiz Fernando , Heringer Gustavo , Viana Neri Andreza , Buttschardt Tillmann , Dudeque Zenni Rafael , Tavares de Menezes Luis Fernando , Zamborlini Saiter Felipe , Reynaud Schaefer Carlos Ernesto Gonçalves , Vieira Hissa Safar Nathália , Pacheco Da Silva Mônica , Simonelli Marcelo , Martins Sebastião V. , Brancalion Pedro Henrique Santin , A. Meira-Neto João Augusto
Published: November 2022

Under the UN-Decade of Ecosystem Restoration and Bonn Challenge, second-growth forest is promoted as a global solution to climate change, degradation and associated losses of biodiversity and ecosystem services. Second growth is often invaded by alien tree species and understanding how this impacts carbon stock and biodiversity recovery is key for restoration planning. We assessed carbon stock and tree diversity recovery in second growth invaded by two
Acacia
species and non-invaded second growth, with associated edge effects, in the Brazilian Atlantic Forest. Carbon stock recovery in non-invaded forests was threefold lower than in invaded forests. Increasingly isolated, fragmented and deforested areas had low carbon stocks when non-invaded, whereas the opposite was true when invaded. Non-invaded forests recovered threefold to sixfold higher taxonomic, phylogenetic and functional diversity than invaded forest. Higher species turnover and lower nestedness in non-invaded than invaded forests underpinned higher abundance of threatened and endemic species in non-invaded forest. Non-invaded forests presented positive relationships between carbon and biodiversity, whereas in the invaded forests we did not detect any relationship, indicating that more carbon does not equal more biodiversity in landscapes with high vulnerability to invasive acacias. To deliver on combined climate change and biodiversity goals, restoration planning and management must consider biological invasion risk.

This article is part of the theme issue ‘Understanding forest landscape restoration: reinforcing scientific foundations for the UN Decade on Ecosystem Restoration’.
Soil resistance and recovery during neotropical forest succession
Authors: van der Sande Masha T. , Powers Jennifer S. , Kuyper Thom W. , Norden Natalia , Salgado-Negret Beatriz , Silva de Almeida Jarcilene , Bongers Frans , Delgado Diego , Dent Daisy H. , Derroire Géraldine , do Espirito Santo Mario Marcos , Dupuy Juan Manuel , Fernandes Geraldo Wilson , Finegan Bryan , Gavito Mayra E. , Hernández-Stefanoni José Luis , Jakovac Catarina C. , Jones Isabel L. , das Dores Magalhães Veloso Maria , Meave Jorge A. , Mora Francisco , Muñoz Rodrigo , Pérez-Cárdenas Nathalia , Piotto Daniel , Álvarez-Dávila Esteban , Caceres-Siani Yasmani , Dalban-Pilon Coralie , Dourdain Aurélie , Du Dan V. , García Villalobos Daniel , Nunes Yule Roberta Ferreira , Sanchez-Azofeifa Arturo , Poorter Lourens
Published: November 2022

The recovery of soil conditions is crucial for successful ecosystem restoration and, hence, for achieving the goals of the UN Decade on Ecosystem Restoration. Here, we assess how soils resist forest conversion and agricultural land use, and how soils recover during subsequent tropical forest succession on abandoned agricultural fields. Our overarching question is how soil resistance and recovery depend on local conditions such as climate, soil type and land-use history. For 300 plots in 21 sites across the Neotropics, we used a chronosequence approach in which we sampled soils from two depths in old-growth forests, agricultural fields (i.e. crop fields and pastures), and secondary forests that differ in age (1–95 years) since abandonment. We measured six soil properties using a standardized sampling design and laboratory analyses. Soil resistance strongly depended on local conditions. Croplands and sites on high-activity clay (i.e. high fertility) show strong increases in bulk density and decreases in pH, carbon (C) and nitrogen (N) during deforestation and subsequent agricultural use. Resistance is lower in such sites probably because of a sharp decline in fine root biomass in croplands in the upper soil layers, and a decline in litter input from formerly productive old-growth forest (on high-activity clays). Soil recovery also strongly depended on local conditions. During forest succession, high-activity clays and croplands decreased most strongly in bulk density and increased in C and N, possibly because of strongly compacted soils with low C and N after cropland abandonment, and because of rapid vegetation recovery in high-activity clays leading to greater fine root growth and litter input. Furthermore, sites at low precipitation decreased in pH, whereas sites at high precipitation increased in N and decreased in C : N ratio. Extractable phosphorus (P) did not recover during succession, suggesting increased P limitation as forests age. These results indicate that no single solution exists for effective soil restoration and that local site conditions should determine the restoration strategies.

This article is part of the theme issue ‘Understanding forest landscape restoration: reinforcing scientific foundations for the UN Decade on Ecosystem Restoration’.
Animal seed dispersal recovery during passive restoration in a forested landscape
Authors: Estrada-Villegas Sergio , Stevenson Pablo R. , López Omar , DeWalt Saara J. , Comita Liza S. , Dent Daisy H.
Published: November 2022

Seed dispersal by animals is key for restoration of tropical forests because it maintains plant diversity and accelerates community turnover. Therefore, changes in seed dispersal during forest restoration can indicate the recovery of species interactions, and yet these changes are rarely considered in forest restoration planning. In this study, we examined shifts in the importance of different seed dispersal modes during passive restoration in a tropical chronosequence spanning more than 100 years, by modelling the proportion of trees dispersed by bats, small birds, large birds, flightless mammals and abiotic means as a function of forest age. Contrary to expectations, tree species dispersed by flightless mammals dominated after 20 years of regeneration, and tree richness and abundance dispersed by each mode mostly recovered to old growth levels between 40 and 70 years post-abandonment. Seed dispersal by small birds declined over time during regeneration, while bat dispersal played a minor role throughout all stages of succession. Results suggest that proximity to old growth forests, coupled with low hunting, explained the prevalence of seed dispersal by animals, especially by flightless mammals at this site. We suggest that aspects of seed dispersal should be monitored when restoring forest ecosystems to evaluate the reestablishment of species interactions.

This article is part of the theme issue ‘Understanding forest landscape restoration: reinforcing scientific foundations for the UN Decade on Ecosystem Restoration’.
Restoration interventions mediate tropical tree recruitment dynamics over time
Authors: Kulikowski Andy J. , Zahawi Rakan A. , Werden Leland K. , Zhu Kai , Holl Karen D.
Published: November 2022

Forest restoration is increasingly heralded as a global strategy to conserve biodiversity and mitigate climate change, yet long-term studies that compare the effects of different restoration strategies on tree recruit demographics are lacking. We measured tree recruit survival and growth annually in three restoration treatments—natural regeneration, applied nucleation and tree plantations—replicated at 13 sites in southern Costa Rica—and evaluated the changes over a decade. Early-successional seedlings had 14% higher survival probability in the applied nucleation than natural regeneration treatments. Early-successional sapling growth rates were initially 227% faster in natural regeneration and 127% faster in applied nucleation than plantation plots but converged across restoration treatments over time. Later-successional seedling and sapling survival were similar across treatments but later-successional sapling growth rates were 39% faster in applied nucleation than in plantation treatments. Results indicate that applied nucleation was equally or more effective in enhancing survival and growth of naturally recruited trees than the more resource-intensive plantation treatment, highlighting its promise as a restoration strategy. Finally, tree recruit dynamics changed quickly over the 10-year period, underscoring the importance of multi-year studies to compare restoration interventions and guide ambitious forest restoration efforts planned for the coming decades.

This article is part of the theme issue ‘Understanding forest landscape restoration: reinforcing scientific foundations for the UN Decade on Ecosystem Restoration’.
The community capacity curve applied to reforestation: a framework to support success
Authors: Herbohn John , Ota Liz , Gregorio Nestor , Chazdon Robin , Fisher Robert , Baynes Jack , Applegate Grahame , Page Tony , Carias Dora , Romero Claudia , Putz Francis E. , Firn Jennifer
Published: November 2022

Community involvement is critical for the success of many interventions designed to promote reforestation. To secure this involvement, it helps to recognize that communities are heterogenous both within and among themselves and possess diverse mixes of livelihood assets required to implement reforestation. We explore the relationship between livelihood assets and reforestation success and outline a conceptual model that we call the community capacity curve (CCC) applied to reforestation. We argue that the shape of the CCC is sigmoidal. Importantly, communities at the lower end of the CCC have limited capacity to implement reforestation projects without substantial and ongoing capacity building and other sorts of support, including through livelihood projects that improve food security and provide cash benefits. Communities at the higher part of the CCC have greater capacity to implement reforestation projects, especially projects focused on biodiversity and environmental services. The CCC can help design, implement, monitor and assess reforestation projects, select appropriate livelihood activities and types of reforestation, select communities suited to a reforestation project, guide implementation and understand projects' successes and failure. The CCC also provides a framework to engage with policy makers and funding bodies to explore the types of support for communities to reforest successfully.

This article is part of the theme issue ‘Understanding forest landscape restoration: reinforcing scientific foundations for the UN Decade on Ecosystem Restoration’.
Placenta-associated adverse pregnancy outcomes in women experiencing mild or severe hyperemesis gravidarum – a systematic review and meta-analysis
Authors: Moberg Tilda , Van der Veeken Lennart , Persad Emma , Hansson Stefan R. , Bruschettini Matteo
Published: November 2022

Background

Nausea and vomiting in pregnancy (NVP) affects 50-80% of pregnant women and is correlated to the level of human chorionic gonadotropin (hCG). Hyperemesis gravidarum (HG) is a severe condition, with an incidence of 0.2-1.5%, characterized by consistent nausea, vomiting, weight loss and dehydration continuing after the second trimester.

Aim

The aim of this systematic review was to investigate a potential correlation between NVP or HG with adverse pregnancy outcomes and hCG levels.

Method

A systematic search in PubMed, Embase and CINAHL Complete was conducted. Studies on pregnant women with nausea in the first or second trimester, reporting either pregnancy outcomes or levels of hCG were included. The primary outcomes were preterm delivery (PTD), preeclampsia, miscarriage, and fetal growth restriction. Risk of bias was assessed using ROBINS-I. The overall certainty of evidence was assessed using GRADE.

Results

The search resulted in 2023 potentially relevant studies; 23 were included. The evidence was uncertain for all outcomes, however women with HG had a tendency to have an increased risk for preeclampsia [odds ratio (OR) 1.18, 95% confidence of interval (CI) 1.03 to 1.35], PTD [OR 1.35, 95% CI 1.13 to 1.61], small for gestational age (SGA) [OR 1.24, 95% CI 1.13 to 1.35], and low birth weight (LBW) [OR 1.35, 95% CI 1.26 to 1.44]. Further, a higher foetal female/male ratio was observed [OR 1.36, 95% CI 1.15 to 1.60]. Meta-analyses were not performed for women with NVP; however, most of these studies indicated that women with NVP have a lower risk for PTD and LBW and a higher risk for SGA, and a higher fetal female/male ratio.

Conclusion

There may be an increased risk in women with HG and a decreased risk in women with NVP for adverse placenta-associated pregnancy outcomes, however the evidence is very uncertain.

PROSPERO:CRD42021281218
Association between maternal breastmilk microbiota composition and rotavirus vaccine response in African, Asian, and European infants: a prospective cohort study
Authors: Mandolo Jonathan , Parker Edward P. K. , Bronowski Christina , Sindhu Kulandaipalayam Natarajan C. , Darby Alistair C. , Cunliffe Nigel A. , Kang Gagandeep , Iturriza-Gómara Miren , Kamng’ona Arox W. , Jere Khuzwayo C.
Published: November 2022

Background

Maternal breastmilk is a source of pre- and pro-biotics that impact neonatal gut microbiota colonisation. Since oral rotavirus vaccines (ORVs) are administered at a time when infants are often breastfed, breastmilk microbiota composition may have a direct or indirect influence on vaccine take and immunogenicity.

Methods

Using standardised methods across sites, we compared breastmilk microbiota composition in relation to geographic location and ORV response in cohorts prospectively followed up from birth to 18 weeks of age in India (n= 307), Malawi (n= 119), and the UK (n= 60).

Results

Breastmilk microbiota diversity was higher in India and Malawi than the UK across three longitudinal samples spanning weeks of life 1 to 13. Dominant taxa such asStreptococcusandStaphylococcuswere consistent across cohorts; however, significant geographic differences were observed in the prevalence and abundance of common and rare genera throughout follow-up. No significant associations were identified between breastmilk microbiota composition and ORV outcomes including seroconversion, post-dose 1 vaccine shedding, and/or post-vaccination rotavirus-specific IgA level.

Conclusions

Our findings suggest that breastmilk microbiota composition may not be a key factor in shaping trends in ORV response within or between countries.