bluuebunny/crossref_metadata_2025 huggingface dataset:
Preclinical characterization and in silico safety assessment of three virulent bacteriophages targeting carbapenem-resistant uropathogenic Escherichia coli
Authors: Dhungana Gunaraj , Nepal Roshan , Houtak Ghais , Bouras George , Vreugde Sarah , Malla Rajani
Published: March 2024

Phage therapy has recently been revitalized in the West with many successful applications against multi-drug-resistant bacterial infections. However, the lack of geographically diverse bacteriophage (phage) genomes has constrained our understanding of phage diversity and its genetics underpinning host specificity, lytic capability, and phage-bacteria co-evolution. This study aims to locally isolate virulent phages against uropathogenic Escherichia coli (E. coli) and study its phenotypic and genomic features. Three obligately virulent Escherichia phages (øEc_Makalu_001, øEc_Makalu_002, and øEc_Makalu_003) that could infect uropathogenic E. coli were isolated and characterized. All three phages belonged to Krischvirus genus. One-step growth curve showed that the latent period of the phages ranged from 15 to 20 min, the outbreak period ~ 50 min, and the burst size ranged between 74 and 127 PFU/bacterium. Moreover, the phages could tolerate a pH range of 6 to 9 and a temperature range of 25–37 °C for up to 180 min without significant loss of phage viability. All phages showed a broad host spectrum and could lyse up to 30% of the 35 tested E. coli isolates. Genomes of all phages were approximately ~ 163 kb with a gene density of 1.73 gene/kbp and an average gene length of ~ 951 bp. The coding density in all phages was approximately 95%. Putative lysin, holin, endolysin, and spanin genes were found in the genomes of all three phages. All phages were strictly virulent with functional lysis modules and lacked any known virulence or toxin genes and antimicrobial resistance genes. Pre-clinical experimental and genomic analysis suggest these phages may be suitable candidates for therapeutic applications.
Photobiomodulation and low-intensity pulsed ultrasound synergistically enhance dental mesenchymal stem cells viability, migration and differentiation: an invitro study
Authors: Shamel Mohamed , Raafat Shereen , El Karim Ikhlas , Saber Shehabeldin
Published: March 2024

Novel methods and technologies that improve mesenchymal stem cells (MSCs) proliferation and differentiation properties are required to increase their clinical efficacy. Photobiomodulation (PBM) and low-intensity pulsed ultrasound (LIPUS) are two strategies that can be used to enhance the regenerative properties of dental MSCs. This study evaluated the cytocompatibility and osteo/odontogenic differentiation of dental pulp, periodontal ligament, and gingival MSCs after stimulation by either PBM or LIPUS and their combined effect. MTT assay, cell migration assay, osteo/odontogenic differentiation by AR staining and ALP activity, and expression of osteo/odontogenic markers (OPG, OC, RUNX2, DSPP, DMP1) by RT-qPCR were evaluated. Statistical analysis was performed using ANOVA, followed by Tukey’s post hoc test, with a p-value of less than 0.05 considered significant. The results showed that combined stimulation by PBM and LIPUS resulted in significantly the highest viability of MSCs, the fastest migration, the most dense AR staining, the most increased ALP activity, and the most elevated levels of osteogenic and odontogenic markers. The synergetic stimulation of PBM and LIPUS can be utilized in cell-based regenerative approaches to promote the properties of dental MSCs.
Racial disparities in initiation of chemotherapy among breast cancer patients with discretionary treatment indication in the state of Georgia
Authors: Collin Lindsay J. , Jones Jade , Nash Rebecca , Switchenko Jeffrey M. , Ward Kevin C. , McCullough Lauren E.
Published: March 2024

Purpose

The majority of breast cancer patients are diagnosed with early-stage estrogen receptor (ER) positive disease. Despite effective treatments for these cancers, Black women have higher mortality than White women. We investigated demographic and clinical factors associated with receipt of chemotherapy among those with a discretionary indication who are at risk for overtreatment.

Methods

Using Georgia Cancer Registry data, we identified females diagnosed with ER positive breast cancer who had a discretionary indication for chemotherapy (2010–2017). We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) associating patient demographic and clinical characteristics with chemotherapy initiation overall, and comparing non-Hispanic Black (NHB) with non-Hispanic White (NHW) women within strata of patient factors.

Results

We identified 11,993 ER positive breast cancer patients with a discretionary indication for chemotherapy. NHB patients were more likely to initiate chemotherapy compared with NHW women (OR = 1.41, 95% CI: 1.28, 1.56). Race differences in chemotherapy initiation were pronounced among those who did not receive Oncotype DX testing (OR = 1.47, 95% CI: 1.31, 1.65) and among those residing in high socioeconomic status neighborhoods (OR = 2.48, 95% CI: 1.70, 3.61). However, we observed equitable chemotherapy receipt among patients who received Oncotype DX testing (OR = 0.90, 95% CI: 0.71, 1.14), were diagnosed with grade 1 disease (OR = 1.00, 95% CI: 0.74, 1.37), and those resided in rural areas (OR = 1.01, 95% CI: 0.76, 1.36).

Conclusion

We observed racial disparities in the initiation of chemotherapy overall and by sociodemographic and clinical factors, and more equitable outcomes when clinical guidelines were followed.
Association between albumin–bilirubin grade and plasma trough concentrations of regorafenib and its metabolites M-2 and M-5 at steady-state in Japanese patients
Authors: Fujita Kazuma , Taguchi Daiki , Fukuda Koji , Yoshida Taichi , Shimazu Kazuhiro , Shinozaki Hanae , Shibata Hiroyuki , Miura Masatomo
Published: March 2024

The aim of the present study was to determine whether the trough plasma concentrations (C0) of regorafenib and its metabolites, the N-oxide metabolite (M-2) and the desmethyl N-oxide metabolite (M-5), in 21 patients receiving regorafenib therapy were affected by albumin-bilirubin (ALBI) grade. Regorafenib was administered at dosages ranging from 40 to 160 mg once daily on a 3-week-on, 1-week-off cycle. C0 values of regorafenib and its major metabolites were measured by high-performance liquid chromatography on day 8 after treatment initiation. The C0 values of regorafenib and metabolites M-2 and M-5 were significantly lower in patients with ALBI grade 2 as compared with grade 1 (P = 0.023, 0.003 and 0.017, respectively). The total C0 of regorafenib and its metabolites was significantly higher in ALBI grade 1 patients relative to grade 2 (3.489 μg/mL vs. 1.48 μg/mL; P = 0.009). The median relative dose intensity (RDI) of patients categorized as ALBI grade 2 was significantly lower than that of grade 1 patients (21.9% vs. 62.9%; P = 0.006). In 15 colorectal cancer patients among the total 21 patients, patients with ALBI grade 2 (n = 9) had a significantly shorter median overall survival time than patients with grade 1 (n = 6; P = 0.013). Administering a low dose of regorafenib to patients with ALBI grade 2 reduces the RDI of regorafenib and lowers treatment efficacy, as an appropriate C0 of regorafenib is not maintained. Monitoring the C0 of regorafenib regularly is necessary to guide dose adjustment.
Exploring the Role of Sickness Absence Coordinators in Implementing Interventions to Reduce Sickness Absence in Public Sector Workplaces in Denmark
Authors: Rasmussen Lene , Nielsen Maj Britt Dahl , Garde Anne Helene , Kristiansen Jesper
Published: March 2024

Purpose

In 2019, an initiative to reduce sickness absence in public sector workplaces in Denmark was introduced. The initiative involved appointing a sickness absence coordinator (SA coordinator) to oversee the implementation of workplace-based sickness absence interventions. Since the role of the SA coordinator is a novel concept introduced as part of the initiative, this study investigates the responsibilities of SA coordinators and the challenges they experienced in fulfilling this role during the implementation process.

Methods

Semi-structured interviews with and observations of SA coordinators from four public sector workplaces were carried out. We collected the first four interviews and observations during the implementation process with follow-up interviews collected at the end of the process. The data were analyzed using thematic analysis.

Results

The SA coordinators all experienced challenges in terms of lack of commitment among the line managers to participate in the intervention. They experienced being seen as a burden rather than a helping hand, and felt that the line managers might have difficulty recognizing the value of the SA coordinators. Potential ways to improve the collaboration between the SA coordinators and the line managers include considering hiring the SA coordinator in-house and incorporation of intervention components into existing activities to accommodate the busyness of the line managers.

Conclusions

To support the SA coordinators in carrying out their role and responsibilities, this study suggests that it is important to ensure commitment to the role, especially among the line managers in order to enhance good working relationships.
Gradient boosted trees for evolving data streams
Authors: Gunasekara Nuwan , Pfahringer Bernhard , Gomes Heitor , Bifet Albert
Published: March 2024

Gradient Boosting is a widely-used machine learning technique that has proven highly effective in batch learning. However, its effectiveness in stream learning contexts lags behind bagging-based ensemble methods, which currently dominate the field. One reason for this discrepancy is the challenge of adapting the booster to new concept following a concept drift. Resetting the entire booster can lead to significant performance degradation as it struggles to learn the new concept. Resetting only some parts of the booster can be more effective, but identifying which parts to reset is difficult, given that each boosting step builds on the previous prediction. To overcome these difficulties, we propose Streaming Gradient Boosted Trees (Sgbt), which is trained using weighted squared loss elicited in XGBoost. Sgbt exploits trees with a replacement strategy to detect and recover from drifts, thus enabling the ensemble to adapt without sacrificing the predictive performance. Our empirical evaluation of Sgbt on a range of streaming datasets with challenging drift scenarios demonstrates that it outperforms current state-of-the-art methods for evolving data streams.
Predictors of Occupational Distress of Catholic Priests on the Eastern Seaboard of the United States
Authors: Kostick Michael D. , Zhu Xihe , Haegele Justin A. , Baker Pete
Published: March 2024

With ever-increasing demands placed upon active priests in the United States, insight into protecting their mental health may help strengthen vocational resilience for individual priests. The purpose of this study was to examine the association of individual variables, workplace characteristics, and physical activity participation with occupational distress levels among Catholic priests. A 22-question survey consisting of a demographic questionnaire, the Clergy Occupational Distress Index, and the International Physical Activity Questionnaire was employed to collect individual variables, workplace characteristics, physical activity participation, and occupational distress levels of Catholic priests from the Eastern seaboard of the United States. Regression analyses showed that the number of years ordained (β = −.24, p < .01) and number of priests residing together (β = −.11, p = .05) were negatively associated with occupational distress levels. Collectively, these demographic, workplace, and physical activity variables accounted for about 10% of the variances in priest participant occupational distress scores. Findings suggest that novice priests may be more susceptible to occupational distress than veteran priests and that those living in multi-priest households tend to show lower levels of occupational distress. (Arch)dioceses may find the results of the current study useful for planning housing situations for priests or to better help novice priests meet the demands of their vocation.
Pharmacokinetic Profile of Brepocitinib with Topical Administration in Atopic Dermatitis and Psoriasis Populations: Strategy to Inform Clinical Trial Design in Adult and Pediatric Populations
Authors: Maleki Farzaneh , Chang Cheng , Purohit Vivek S. , Nicholas Timothy
Published: March 2024

Introduction

Topical brepocitinib, a tyrosine kinase (TYK)2/Janus kinase (JAK)1 inhibitor, is in development for psoriasis (PsO) and atopic dermatitis (AD). Quantitative analyses of prior clinical trial data were used to inform future clinical trial designs.

Methods

Two phase 2b studies in patients with AD and PsO were used to characterize the amount of topical brepocitinib and the resultant systemic trough concentration (CTrough) using a linear mixed-effects regression (LMER). This model was used to predict brepocitinib systemic CTrough for higher treated body surface areas (BSAs) in adults and children. Information from non-clinical and clinical trials with oral brepocitinib was leveraged to set safety thresholds. This combined approach was used to inform future dose-strength selection and treated BSA limits.

Results

Data from 256 patients were analyzed. Patient type, dose strength, and frequency had significant impacts on the dose–exposure relationship. Systemic concentration in patients with PsO was predicted to be 45% lower than in patients with AD from the same dose. When topically applied to the same percentage BSA, brepocitinib systemic exposures are expected to be comparable between adults and children. The systemic steady-state exposure after 3% once daily and twice daily (2 mg/cm2) cream applied to less than 50% BSA in patients with AD and PsO, respectively, maintains at least a threefold margin to non-clinical safety findings and clinical hematologic markers.

Conclusion

The relationship between the amount of active drug applied and brepocitinib systemic CTrough, described by LMER, may inform the development strategy for dose optimization in the brepocitinib topical program.
Expanding Education Researchers’ Access to Classroom Observation Data With a Remote and Cost-Effective Video Data Collection Protocol
Authors: McLean Leigh , Espinoza Paul , Tilley Kati , Foote Lori , Jones Nathan , Kelcey Ben
Published: March 2024

The onset of the COVID-19 pandemic and associated long-term shifts to virtual instruction among most US schools presented notable challenges among education researchers. Ongoing projects conducted in school settings experienced sudden losses of access to teacher and student participants, in many cases leading to severe interruptions to data collection efforts. Perhaps most notably, upon returns to in-person instruction in the 2021/22 academic year most schools instigated strict policies limiting the number of non-school personnel who could enter school buildings, including researchers conducting in-person data collections. As such, many researchers had to find alternative means to gather data. In this paper, we offer a new protocol that we created in response to these challenges that allows for the secure and fully remote collection of video data in school settings. This new protocol not only addressed the immediate needs of the focal study but also addresses some of the most notable barriers to collecting classroom video data in the field of education research at large. In this paper, we describe the initial development and application of this protocol among a local study of elementary teachers, as well as the scaling of this protocol in a study of elementary teachers in multiple states. It is our hope that this protocol can expand education researchers’, practitioners’, and policymakers’ access to classroom video data.
Pictorial and Apictorial Polygonal Jigsaw Puzzles from Arbitrary Number of Crossing Cuts
Authors: Harel Peleg , Shahar Ofir Itzhak , Ben-Shahar Ohad
Published: March 2024

Jigsaw puzzle solving, the problem of constructing a coherent whole from a set of non-overlapping unordered visual fragments, is fundamental to numerous applications, and yet most of the literature of the last two decades has focused thus far on less realistic puzzles whose pieces are identical squares. Here we formalize a new type of jigsaw puzzle where the pieces are general convex polygons generated by cutting through a global polygonal shape/image with an arbitrary number of straight cuts, a generation model inspired by the celebrated Lazy caterer’s sequence. We analyze the theoretical properties of such puzzles, including the inherent challenges in solving them once pieces are contaminated with geometrical noise. To cope with such difficulties and obtain tractable solutions, we abstract the problem as a multi-body spring-mass dynamical system endowed with hierarchical loop constraints and a layered reconstruction process. We define evaluation metrics and present experimental results on both apictorial and pictorial puzzles to show that they are solvable completely automatically.
Study of prevalence, risk factors for acute kidney injury, and mortality in liver cirrhosis patients
Authors: Mohan Pooja Basthi , Nagaraju Shankar Prasad , Musunuri Balaji , Rajpurohit Siddheesh , Bhat Ganesh , Shetty Shiran
Published: March 2024

Introduction

Acute kidney injury (AKI) occurs frequently in patients with end-stage liver disease and cirrhosis and is associated with increased short-term mortality. This study aims to study the prevalence and risk factors associated with AKI development and mortality in cirrhosis of liver patients.

Methodology

In the current prospective study, hospitalized patients with liver cirrhosis from October 2021 to March 2023 were recruited. Demographic, clinical, and laboratory data were collected, which included, the etiology of cirrhosis, comorbidities, severity of liver disease, and relevant biochemical parameters. The patient was followed up for 90 days to record the clinical outcome. The statistical software SPSS was utilized to conduct the analysis.

Results

Of 364 liver cirrhosis patients, 25.2% (n, 92) had AKI and belonged to an average age of 51.54 ± 11.82 years. The majority of individuals in the study were males (90.4%), and alcohol (63.4%) was the most common etiology of liver cirrhosis. The present study showed that higher level of direct bilirubin (p = 0.011) and MELD score (p = 0.0001) were identified as significant risk factors for AKI development in patients with liver cirrhosis. Regarding mortality, the significant risk factors were the presence of AKI (p = 0.045) and MELD score (p = 0.025). Among AKI patients, 90-day mortality rates were higher in patients with acute tubular necrosis (p value = 0.010) and stage 3 AKI (p value = 0.001).

Conclusion

AKI is common in cirrhosis of liver patients. Elevated levels of direct bilirubin and MELD score emerged as significant factors associated with AKI development. Furthermore, AKI and MELD scores were identified as independent risk factors for mortality at both 30 and 90 days. Survival rates were influenced by both the type and stage of AKI; AKI stage 3 and ATN patients had significantly higher mortality rate. Early AKI detection and management are crucial for reducing mortality risk in liver cirrhosis patients.
Optimization for cost-effective design of water distribution networks: a comprehensive learning approach
Authors: Bala Indu , Yadav Anupam , Kim Joong Hoon
Published: March 2024

The Comprehensive Learning Gravitational Search Algorithm (CLGSA) has demonstrated its effectiveness in solving continuous optimization problems. In this research, we extended the CLGSA to tackle NP-hard combinatorial problems and introduced the Discrete Comprehensive Learning Gravitational Search Algorithm (D-CLGSA). The D-CLGSA framework incorporated a refined position and velocity update scheme tailored for discrete problems. To evaluate the algorithm's efficiency, we conducted two sets of experiments. Firstly, we assessed its performance on a diverse range of 24 benchmarks encompassing unimodal, multimodal, composite, and special discrete functions. Secondly, we applied the D-CLGSA to a practical optimization problem involving water distribution network planning and management. The D-CLGSA model was coupled with the hydraulic simulation solver EPANET to identify the optimal design for the water distribution network, aiming for cost-effectiveness. We evaluated the model's performance on six distribution networks, namely Two-loop network, Hanoi network, New-York City network, GoYang network, BakRyun network, and Balerma network. The results of our study were promising, surpassing previous studies in the field. Consequently, the D-CLGSA model holds great potential as an optimizer for economically and reliably planning and managing water networks.
Elderly patients with hormone receptor-positive HER2-negative metastatic breast cancer treated with CDK4/6 inhibitors in a multicentre cohort
Authors: Pla Helena , Felip Eudald , Obadia Verónica , Pernas Sonia , Viñas Gemma , Margelí Mireia , Fort-Culillas Roser , Del Barco Sonia , Sabaté Nuria , Fort Eduard , Lezcano Clara , Cirauqui Beatriz , Quiroga Vanesa , Stradella Agostina , Gil Gil Miguel , Esteve Anna , Recalde Sabela
Published: March 2024

Introduction

Cyclin-dependent kinases 4/6 inhibitors (CDK 4/6i) combined with endocrine therapy have become the gold standard in hormone receptor-positive (HR +) HER2-negative (HER2-) metastatic breast cancer (MBC). However, there is a significant lack of data regarding the efficacy and safety of these treatments in elderly patients. We present the results of a real-world data (RWD) cohort stratified by age at treatment initiation (≥ 70 years compared to patients < 70 years).

Methods

Clinico-pathological data of HR + HER2- MBC patients who were candidates for CDK4/6i therapy between January 2017 and December 2020 at the Institut Català d'Oncologia (Spain) were retrospectively collected. The primary goal was to assess Progression-Free Survival (PFS), Overall Survival (OS), and safety outcomes within this patient population.

Results

A total of 274 patients with MBC who received CDK4/6i treatment were included in the study. Among them, 84 patients (30.8%) were aged ≥ 70 years, with a mean age of 75, while 190 patients (69.2%) were under the age of 70, with a mean age of 55.7 years. The most frequently observed grade 3–4 toxicity was neutropenia, with similar rates in both the < 70 group (43.9%) and the ≥ 70 group (47.9%) (p = 0.728). The median Progression-Free Survival (mPFS) for the first-line CDK4/6i treatment was 22 months (95% CI, 15.4–39.8) in the < 70 group and 20.8 months (95% CI 11.2–NR) in the ≥ 70 group (p = 0.67). Similarly, the median PFS for the second-line CDK4/6i treatment was 10.4 months (95% CI, 7.4–15.1) and 7.1 months (95% CI 4.4–21.3) (p = 0.79), respectively. Median overall survival (mOS) was not reached either for the first- and second-line treatment.

Conclusions

Our RWD suggests that elderly patients, when compared to those under 70, experience similar survival outcomes and exhibit comparable tolerance for CDK4/6i therapy.
Exploring neuro-symbolic AI applications in geoscience: implications and future directions for mineral prediction
Authors: Chen Weilin , Ma Xiaogang , Wang Zhe , Li Wenjia , Fan Chao , Zhang Jiyin , Que Xiang , Li Chenhao
Published: March 2024

The integration of machine learning (ML) and deep learning (DL) into geoscience has experienced a pronounced uptick in recent years, a trend propelled by the intricate nature of geosystems and the abundance of data they produce. These computational methods have been harnessed across a spectrum of geoscientific challenges, from climate modeling to seismic analysis, exhibiting notable efficacy in extracting valuable insights from intricate geological datasets for applications such as mineral prediction. A thorough analysis of the literature indicates a marked escalation in AI-centric geoscience research starting in 2018, characterized by a predictive research orientation and a persistent focus on key computational terms. The thematic network and evolution analyses underscore the enduring prominence of “deep learning” and “machine learning” as pivotal themes, alongside progressive developments in “transfer learning” and “big data”. Despite these advancements, other methodologies have garnered comparatively lesser focus. While ML and DL have registered successes in the realm of mineral prediction, their amalgamation with domain-specific knowledge and symbolic reasoning could further amplify their interpretability and operational efficiency. Neuro-Symbolic AI (NSAI) emerges as a cutting-edge approach that synergizes DL’s robust capabilities with the precision of symbolic reasoning, facilitating the creation of models that are both powerful and interpretable. NSAI distinguishes itself by surmounting traditional ML constraints through the incorporation of expert insights and delivering explanatory power behind its predictive prowess, rendering it particularly advantageous for mineral prediction tasks. This literature review delves into the promising potential of NSAI, alongside ML and DL, within the geoscientific domain, spotlighting mineral prediction as a key area of focus. Despite the hurdles associated with infusing domain expertise into symbolic formats and mitigating biases inherent in symbolic reasoning, the application of NSAI in the realm of critical mineral prediction stands to catalyze a paradigm shift in the field. By bolstering prediction accuracy, enhancing decision-making processes, and fostering sustainable resource exploitation, NSAI holds the potential to significantly reshape geoscience’s future trajectory.
A Review of Seagrass Cover, Status and Trends in Africa
Authors: Mwikamba Edward Mutwiri , Githaiga Michael N. , Briers Robert A. , Huxham Mark
Published: March 2024

The recognition of the benefits that seagrasses contribute has enhanced the research interest in these marine ecosystems. Seagrasses provide critical goods and services and support the livelihoods of millions of people. Despite this, they are declining around the globe. To conserve these ecosystems, it is necessary to understand their extent and the drivers leading to their loss. However, global seagrass cover estimates are highly uncertain and there are large regional data gaps, especially in the African continent. This work reviewed all available data on the extent of seagrass cover, evidence of changes in cover and drivers of this change in Africa, to inform management and conservation approaches across the continent and identify gaps in knowledge. Using a systematic review and expert consultation, 43 relevant articles were identified. Of the 41 African countries with a coastline, 27% had no data on seagrass cover. For 44%, data were available for some parts of their coastline, while 29% had data for their entire coastline. Quantitative information on trends in seagrass cover change was only available from three countries. The study identified 32 suggested drivers of seagrass cover loss, with impacts from fishing mentioned most frequently. Direct anthropogenic drivers accounted for 66.7% of the mentions, while climate and biologically induced drivers accounted for 22.7% and 10.6%, respectively. This study demonstrates the need for better estimates of seagrass extent, in at least 70% of relevant African nations, and major gaps in our understanding of the drivers of seagrass decline in Africa.
In vivo evaluation of a Nano-enabled therapeutic vitreous substitute for the precise delivery of triamcinolone to the posterior segment of the eye
Authors: Naik Kruti , du Toit Lisa Claire , Ally Naseer , Choonara Yahya Essop
Published: March 2024

This study focused on the design of a thermoresponsive, nano-enabled vitreous substitute for the treatment of retinal diseases. Synthesis of a hydrogel composed of hyaluronic acid and a poloxamer blend was undertaken. Poly(D,L-lactide-co-glycolide) acid nanoparticles encapsulating triamcinolone acetonide (TA) were synthesised with a spherical morphology and mean diameter of ~ 153 nm. Hydrogel fabrication and nanoparticle loading within the hydrogel was confirmed via physicochemical analysis. Gelation studies indicated that hydrogels formed in nine minutes and 10 min for the unloaded and nanoparticle-loaded hydrogels, respectively. The hydrogels displayed in situ gel formation properties, and rheometric viscoelastic studies indicated the unloaded and loaded hydrogels to have modulus values similar to those of the natural vitreous at 37 °C. Administration of the hydrogels was possible via 26G needles allowing for clinical application and drug release of triamcinolone acetonide from the nanoparticle-loaded hydrogel, which provided sustained in vitro drug release over nine weeks. The hydrogels displayed minimal swelling, reaching equilibrium swelling within 12 h for the unloaded hydrogel, and eight hours for the nanoparticle-loaded hydrogel. Biodegradation in simulated vitreous humour with lysozyme showed < 20% degradation within nine weeks. Biocompatibility of both unloaded and loaded hydrogels was shown with mouse fibroblast and human retinal pigment epithelium cell lines. Lastly, a pilot in vivo study in a New Zealand White rabbit model displayed minimal toxicity with precise, localised drug release behaviour, and ocular TA levels maintained within the therapeutic window for the 28-day investigation period, which supports the potential applicability of the unloaded and nanoparticle-loaded hydrogels as vitreous substitutes that function as drug delivery systems following vitrectomy surgery.

Graphical Abstract
Catalyzing Progress: a Comprehensive Review of Cancer Rehabilitation Education for Rehabilitation Specialists
Authors: Newell Alaina , Malhotra Jasmine , Raoof Elizabeth , Thess Melissa , Grasso Patrick , Power Katherine , Wisotzky Eric
Published: March 2024

Purpose of Review

The growing population of cancer survivors shows the crucial role of cancer rehabilitation. Despite advancement in cancer treatments, a significant proportion of survivors experience physical and cognitive impairments. This paper looks to review the current state of cancer rehabilitation education, focusing on interdisciplinary rehabilitation specialists. Physician education in cancer rehabilitation is examined, revealing disparities among programs and the slow integration into PM&R residency training.

Recent Findings

The number of physician-focused cancer rehabilitation fellowships are growing and significant variation exists among these programs. Therapist education in oncology rehabilitation is also expanding including certification programs with the role of organizations such as APTA, AOTA, and ASHA. Accreditation standards from CARF, NCCN, and CoC can provide potential benchmarks for practice requirements alongside the advancements made by AAPM&R, ACRM, and MASCC.

This paper notes the strides made in cancer rehabilitation education but also highlights the persistent gaps that exist. While there are promising findings, there are also large opportunities for future growth in cancer rehabilitation education. Our hope is that this exploration can inspire expanding opportunities for growth within the interdisciplinary field of cancer rehabilitation.
A Critical Review of Literature on Social Media and Developmental Communication Disability: Implications for Future Social Media and Generative AI Research
Authors: Hemsley Bronwyn , Given Fiona , Almond Barbara , Cooper Jenna , Smith Rebecca , Young Kirsty , Wright Evana
Published: March 2024

Purpose of Review

The widespread use of social media and recent development and use of generative artificial intelligence (GenAI) has implications for the advancement of inclusive communication technologies to benefit people with developmental communication disability. This paper synthesises and critiques recent research on social media use in populations with developmental communication disability, discusses the intersection of social media and GenAI that could impact this population, and provides directions for future research.

Recent Findings

There is encouraging growth in the use of innovative methods to gather the views of people with developmental communication disability on their use of social media, advancing understanding of the risks they face and how they and their supporters manage these risks. However, there continues an underutilization of social media data published by and with people with developmental communication disability and a lack of co-design. Moving beyond patterns and purposes of use, future inclusive and co-designed research with this population should (a) include social media data, whether independently or co-produced with supporters; (b) explore the under-researched legal, ethical, and safety issues; (c) measure the outcomes and impact of social media publication in relation to the user or user group’s emancipation, education, and enablement; and (d) consider the impact of GenAI on social media use for this group.

Continued attention to the safe and enjoyable use of social media for all those who wish to use it, and foundational research on the uptake and use of GenAI, will be important to understand and support the advanced communication technology support needs of people with developmental communication disability. To inform future advances in both social media and GenAI for populations with developmental communication disability, future research directions are proposed.
Association between Mediterranean diet and dementia and Alzheimer disease: a systematic review with meta-analysis
Authors: Nucci Daniele , Sommariva Andrea , Degoni Luca Mario , Gallo Giulia , Mancarella Matteo , Natarelli Federica , Savoia Antonella , Catalini Alessandro , Ferranti Roberta , Pregliasco Fabrizio Ernesto , Castaldi Silvana , Gianfredi Vincenza
Published: March 2024

Background

Dementia affects 5–8% of the population aged over 65 years (~50 million worldwide). Several factors are associated with increased risk, including diet. The Mediterranean diet (MedDiet) has shown potential protective effects against several chronic diseases.

Aims

This systematic review with meta-analysis aim was to assess the association between adherence to the MedDiet and the risk of dementia in the elderly.

Methods

PRISMA-2020 guidelines were followed. PubMed/MEDLINE and Scopus were searched on 17 July 2023. The Newcastle–Ottawa Scale tool was used to assess the risk of bias. The protocol was pre-registered in PROSPERO (registration number: CRD 42023444368). Heterogeneity was assessed using the I2 test. Publication bias was assessed by visual inspection of the funnel plot and by Egger’s regression asymmetry test. The final effect size was reported as OR or HR, depending on the study design of the included studies.

Results

Out of 682 records, 21 were included in the analysis. The pooled OR was 0.89 (95% CI = 0.84–0.94) based on 65,955 participants (I2 = 69.94). When only cohort studies were included, HR was 0.84 (95% CI = 0.76–0.94) based on 55,205 participants (I2 = 89.70). When only Alzheimer Disease was considered OR was 0.73 (95% CI = 0.62–0.85) based on 38,292 participants (I2 = 63.85).

Discussion

Despite the relatively low risk reduction associated with higher adherence to MedDiet among elderly, it should be considered that this population is the most affected.

Conclusions

Adherence to MedDiet could be an effective non-pharmacological measure to reduce the burden of dementia, even among elderly.
Fundamentals of Dispersed Multiphase Flows
Authors: Balachandar S.
Published: March 2024

Dispersed multiphase flows are at the heart of many geophysical, environmental, industrial, and energy applications. Volcanic eruptions, rain formation, powder snow avalanches, sediment transport, and dust storms are some classic examples from the environment, while industrial applications include fluidized beds, slurry transport, fuel injection, cyclone separators, and plasma coating, to name a few. Although each application is unique, they share significant commonalities in the underlying dispersed multiphase-flow physics that govern their dynamics. This book takes a rigorous approach to explaining the complex interconnected physical processes that are at play, before developing different classes of mathematical models and numerical techniques that are appropriate for different regimes of dispersed multiphase flows. Containing many examples and over 100 exercises, it is suitable for use as a graduate-level textbook as well as a reference for researchers who want to model and simulate a multiphase flow phenomenon in their application.
Wireless Communications
Authors: Rappaport Theodore S.
Published: March 2024

Now reissued by Cambridge University Press, the updated second edition of this definitive textbook provides an unrivaled introduction to the theoretical and practical fundamentals of wireless communications. Key technical concepts are developed from first principles, and demonstrated to students using over 50 carefully curated worked examples. Over 200 end-of-chapter problems, based on real-world industry scenarios, help cement student understanding. The book provides a thorough coverage of foundational wireless technologies, including wireless local area networks (WLAN), 3G systems, and Bluetooth along with refreshed summaries of recent cellular standards leading to 4G and 5G, insights into the new areas of mobile satellite communications and fixed wireless access, and extra homework problems. Supported online by a solutions manual and lecture slides for instructors, this is the ideal foundation for senior undergraduate and graduate courses in wireless communications.
The late-Quaternary megafauna extinctions: Patterns, causes, ecological consequences and implications for ecosystem management in the Anthropocene
Authors: Svenning Jens-Christian , Lemoine Rhys T. , Bergman Juraj , Buitenwerf Robert , Le Roux Elizabeth , Lundgren Erick , Mungi Ninad , Pedersen Rasmus Ø.
Published: March 2024

Across the last ~50,000 years (the late Quaternary) terrestrial vertebrate faunas have experienced severe losses of large species (megafauna), with most extinctions occurring in the Late Pleistocene and Early to Middle Holocene. Debate on the causes has been ongoing for over 200 years, intensifying from the 1960s onward. Here, we outline criteria that any causal hypothesis needs to account for. Importantly, this extinction event is unique relative to other Cenozoic (the last 66 million years) extinctions in its strong size bias. For example, only 11 out of 57 species of megaherbivores (body mass ≥1,000 kg) survived to the present. In addition to mammalian megafauna, certain other groups also experienced substantial extinctions, mainly large non-mammalian vertebrates and smaller but megafauna-associated taxa. Further, extinction severity and dates varied among continents, but severely affected all biomes, from the Arctic to the tropics. We synthesise the evidence for and against climatic or modern human (Homo sapiens) causation, the only existing tenable hypotheses. Our review shows that there is little support for any major influence of climate, neither in global extinction patterns nor in fine-scale spatiotemporal and mechanistic evidence. Conversely, there is strong and increasing support for human pressures as the key driver of these extinctions, with emerging evidence for an initial onset linked to pre-sapienshominins prior to the Late Pleistocene. Subsequently, we synthesize the evidence for ecosystem consequences of megafauna extinctions and discuss the implications for conservation and restoration. A broad range of evidence indicates that the megafauna extinctions have elicited profound changes to ecosystem structure and functioning. The late-Quaternary megafauna extinctions thereby represent an early, large-scale human-driven environmental transformation, constituting a progenitor of the Anthropocene, where humans are now a major player in planetary functioning. Finally, we conclude that megafauna restoration via trophic rewilding can be expected to have positive effects on biodiversity across varied Anthropocene settings.
Ailments of the Soul
Authors: Beran Ondřej
Published: March 2024

The paper aims to trace the distinctive character of the talk of the soul and to disentangle it from the talk of the mind. The key context will be the way in which we talk about souls that are ailing. As a point of departure, I use the later Wittgenstein’s notion of the soul as anti‐dualist and anti‐substantive, which brings it close to Dennett’s or Davidson’s philosophy of mind, but which Wittgensteinian ethicists have elaborated upon as concerned with matters of good and evil, and beauty. In relation to these concerns, the sense of the ailing soul is different from issues relating to mental health. I then discuss cases of ailments of the soul that would be misleading to analyse as matters of mental health (issues): addiction, racism, and environmental grief. I conclude with a plea for maintaining the talk of the soul as helpful for making sense of existential or beauty‐ or morality‐related ailments, yet as something that does not necessarily subscribe to any doctrine of the soul as a substance. In support, I also use arguments from the spheres of eco‐theology and public theology.
Developmental Channeling and Evolutionary Dappling
Authors: Ramsey Grant , Villegas Cristina
Published: March 2024

The developmental properties of organisms play important roles in the generation of variation necessary for evolutionary change. But how can individual development steer the course of evolution? To answer this question, we introduce developmental channeling as a disposition of individual organisms that shapes their possible developmental trajectories and evolutionary dappling as an evolutionary outcome in which the space of possible organismic forms is dappled—it is only partially filled. We then trace out the implications of the channeling-dappling framework for contemporary debates in the philosophy of evolution, including evolvability, reciprocal causation, and the extended evolutionary synthesis.
An Empire of Development: American Political Thought in Transnational Perspective
Authors: ADALET BEGÜM
Published: March 2024

This article offers a reconceptualization of US empire by foregrounding a central concept of its theory and practice: development, an ideology and attendant set of material practices that purport to uplift a defined population through political, economic, and social interventions. Because developmental ideology promises benefits and allocates specific roles to different groups, it has worked as a racializing technology, not only defining and assigning clusters of people to hierarchies of different stages but also establishing possibilities, however limited, for movement between these stages. The article demonstrates how developmental ideas and practices have been persistent, if flexible, features across the racialized government of formerly enslaved persons and Native Americans after the Civil War, overseas expansion to the Philippines at the turn of the nineteenth century, and US participation in transnational debates about empire in the early twentieth century and its pursuit of global hegemony after World War II.
Insights from 20 years of mammal population research in Indonesia
Authors: Ardiantiono  , Pinondang Irene M.R. , Chandradewi Desy S. , Semiadi Gono , Pattiselanno Freddy , Supriatna Jatna , Tasirin Johny S. , Winarni Nurul L. , Voigt Maria , Bull Joseph W. , Humle Tatyana , Deere Nicolas J. , Struebig Matthew J.
Published: March 2024

Mammal populations are declining in biodiverse tropical regions. Global analyses have identified Indonesia as a hotspot of vertebrate decline, although relatively few data are available to substantiate these claims. We reviewed research articles published during 2000–2020 on 104 medium-sized to large terrestrial mammal species found in Indonesia to help inform conservation management and future research. We identified 308 peer-reviewed studies published in English or Bahasa Indonesia, with an increase in publication rate (articles published per year) over time. Studies of species distributions dominated the literature, followed by publications on abundance, species diversity and combinations of these topics. Most publications concerned single-species studies conducted at a single location and a single point in time. We identify four key issues that should be addressed by future research and conservation efforts: (1) disproportionate focus on a small number of species; (2) geographical bias towards west Indonesia (Sumatra, Kalimantan and Java–Bali), with few published studies from central (Sulawesi, Nusa Tenggara and Maluku) and east (Papua) Indonesia; (3) limitations to survey design, sampling effort and data analysis; and (4) lack of long-term wildlife population studies. We also note challenges local researchers face in publishing their studies in international journals because of language barriers and costs. Greater use of existing biodiversity data and continued capacity building for local researchers, particularly those in central and east Indonesia, are critical to effectively guide future wildlife monitoring and improve the conservation status of Indonesian mammals.
No relationship between male pubertal timing and depression – new insights from epidemiology and Mendelian randomization
Authors: Hirtz Raphael , Grasemann Corinna , Hölling Heike , von Holt Björn-Hergen , Albers Nicola , Hinney Anke , Hebebrand Johannes , Peters Triinu
Published: March 2024

Background

In males, the relationship between pubertal timing and depression is understudied and less consistent than in females, likely for reasons of unmeasured confounding. To clarify this relationship, a combined epidemiological and genetic approach was chosen to exploit the methodological advantages of both approaches.

Methods

Data from 2026 males from a nationwide, representative study were used to investigate the non-/linear relationship between pubertal timing defined by the age at voice break and depression, considering a multitude of potential confounders and their interactions with pubertal timing. This analysis was complemented by Mendelian randomization (MR), which is robust to inferential problems inherent to epidemiological studies. We used 71 single nucleotide polymorphisms related to pubertal timing in males as instrumental variable to clarify its causal relationship with depression based on data from 807 553 individuals (246 363 cases and 561 190 controls) by univariable and multivariable MR, including BMI as pleiotropic phenotype.

Results

Univariable MR indicated a causal effect of pubertal timing on depression risk (inverse-variance weighted: OR 0.93, 95%-CI [0.87–0.99)], p = 0.03). However, this was not confirmed by multivariable MR (inverse-variance weighted: OR 0.95, 95%-CI [0.88–1.02)], p = 0.13), consistent with the epidemiological approach (OR 1.01, 95%-CI [0.81–1.26], p = 0.93). Instead, the multivariable MR study indicated a causal relationship of BMI with depression by two of three methods.

Conclusions

Pubertal timing is not related to MDD risk in males.