bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved Child Feces Management Mediates Reductions in Childhood Diarrhea from an On-Site Sanitation Intervention: Causal Mediation Analysis of a Cluster-Randomized Trial in Rural Bangladesh
Authors: Contreras Jesse D. , Islam Mahfuza , Mertens Andrew , Pickering Amy J. , Arnold Benjamin F. , Benjamin-Chung Jade , Hubbard Alan E. , Rahman Mahbubur , Unicomb Leanne , Luby Stephen P. , Colford John M. , Ercumen Ayse
Published: March 2024

Background

The WASH benefits Bangladesh trial multi-component sanitation intervention reduced diarrheal disease among children < 5 years. Intervention components included latrine upgrades, child feces management tools, and behavioral promotion. It remains unclear which components most impacted diarrhea.

Methods

We conducted mediation analysis within a subset of households (n = 720) from the sanitation and control arms. Potential mediators were categorized into indicators of latrine quality, latrine use practices, and feces management practices. We estimated average causal mediation effects (ACME) as prevalence differences (PD), defined as the intervention’s effect on diarrhea through its effect on the mediator.

Results

The intervention improved all indicators compared to controls. We found significant mediation through multiple latrine use and feces management practice indicators. The strongest mediators during monsoon seasons were reduced open defecation among children aged < 3 and 3–8 years, and increased disposal of child feces into latrines. The strongest mediators during dry seasons were access to a flush/pour-flush latrine, reduced open defecation among children aged 3–8 years, and increased disposal of child feces into latrines. Individual mediation effects were small (PD = 0.5–2 percentage points) compared to the overall intervention effect but collectively describe significant mediation pathways.

Discussion

The effect of the WASH Benefits Bangladesh sanitation intervention on diarrheal disease was mediated through improved child feces management and reduced child open defecation. Although the intervention significantly improved latrine quality, relatively high latrine quality at baseline may have limited benefits from additional improvements. Targeting safe child feces management may increase the health benefits of rural sanitation interventions.
Ice volume and thickness of all Scandinavian glaciers and ice caps
Authors: Frank Thomas , van Pelt Ward Jan Jacobus
Published: March 2024

We present a new map of bed topography and ice thickness together with a corresponding ice volume estimate representative of the years ~2010 for all Scandinavian ice caps and glaciers. Starting from surface observations, we invert for ice thickness by iteratively running an innovative ice dynamics model on a distributed grid and updating bed topography until modelled and observed glacier dynamics as represented by their rate of surface elevation change (dh/dt) fields align. The ice flow model used is the instructed glacier model (Jouvet and Cordonnier, 2023, Journal of Glaciology 1–15), a generic physics-informed deep-learning emulator that models higher-order ice flow with high-computational efficiency. We calibrate the modelled thicknesses against >11 000 ice thickness observations, resulting in a final ice volume estimate of 302.7 km3 for Norway, 18.4 km3 for Sweden and 321.1 km3 for the whole of Scandinavia with an error estimate of ~

$\pm 11\%$

. The validation statistics computed indicate good agreement between modelled and observed thicknesses (RMSE = 55 m, Pearson's r = 0.87, bias = 0.8 m), outperforming all other ice thickness maps available for the region. The modelled bed shapes thus provide unprecedented detail in the subglacial topography, especially for ice caps where we produce the first maps that show ice-dynamically realistic flow features.
Beyond the “Historiographical Monroe Doctrine”: The Latin American Left and the World
Authors: Chase Michelle
Published: March 2024

This essay reviews the following works:

Latin America and the Global Cold War. Edited by Thomas C. Field Jr., Stella Krepp, and Vanni Pettinà. Chapel Hill: University of North Carolina Press, 2020. Pp. 440. $42.50 hardcover, $29.99 e-book. ISBN: 9781469655697.

La imagen tricontinental: La feminidad, el Che Guevara, y el imperialismo a través del arte gráfico de la OSPAAAL. By Alberto García Molinero. Santiago de Chile: Ariadna Ediciones, 2022. Open access: http://ariadnaediciones.cl/images/pdf/LaImagenTricontinental.pdf.

From the Tricontinental to the Global South: Race, Radicalism, and Transnational Solidarity. By Anne Garland Mahler. Durham, NC: Duke University Press, 2018. Pp. xi + 347. $28.95 paperback. ISBN: 9780822371250.

Toward a Global History of Latin America’s Revolutionary Left. Edited by Tanya Harmer and Alberto Martín Álvarez. Gainesville: University Press of Florida, 2021. Pp. xi + 301. $90.00 hardcover. ISBN: 9781683401698.

No Barrier Can Contain It: Cuban Antifascism and the Spanish Civil War. By Ariel Mae Lambe. Chapel Hill: University of North Carolina Press, 2019. Pp. xvi + 310. $37.50 paperback. ISBN: 9781469652856.

The Tricontinental Revolution: Third World Radicalism and the Cold War. Edited by R. Joseph Parrott and Mark Atwood Lawrence. Cambridge: Cambridge University Press, 2022. Pp. xvii + 365. $120.00 hardcover. ISBN: 9781316519110.

South-South Solidarity and the Latin American Left. By Jessica Stites Mor. Madison: University of Wisconsin Press, 2022. Pp. xix + 266. $79.95 hardcover. ISBN: 9780299336103.

Revolution in Development: Mexico and the Governance of the Global Economy. By Christy Thornton. Oakland: University of California Press, 2021. Pp. 301. $29.95 paperback. ISBN: 9780520297166.
Refugee Protection through Safeguarding Intangible Cultural Heritage of the Home Country and Refugee Journey
Authors: Al Shallah Sherine
Published: March 2024

The legal literature on refugee cultural heritage is limited, and cultural rights are part of the law that appropriately addresses refugee cultural heritage issues. Cultural heritage is integral to the definition of refugees; refugee protection must include safeguarding refugee cultural heritage.1 This Article reviews international law around refugees’ intangible cultural heritage, which incorporates refugee relationships with their tangible cultural heritage.2 It also frames the discussion around refugee intangible cultural heritage in a holistic paradigm that consolidates “refugee home heritage” (refugee intangible cultural heritage of home country) and “refuge heritage” (refugee intangible cultural heritage of refugee journey from persecution or conflict to resettlement or return). The Article finds that, whereas the international law framework lays the groundwork for such a holistic paradigm, international and national laws and state policy approaches must be reformed to achieve refugee protection in line with international obligations.
Childhood unpredictability research within the developmental psychopathology framework: Advances, implications, and future directions
Authors: Doom Jenalee R. , Han Deborah , Rivera Kenia M. , Tseten Tenzin
Published: March 2024

Greater unpredictability in childhood from the level of the caregiver-child dyad to broader family, home, or environmental instability is consistently associated with disruptions in cognitive, socioemotional, behavioral, and biological development in humans. These findings are bolstered by experimental research in non-human animal models suggesting that early life unpredictability is an important environmental signal to the developing organism that shapes neurodevelopment and behavior. Research on childhood unpredictability has surged in the past several years, guided in part by theoretical grounding from the developmental psychopathology framework (shaped largely by Dr. Dante Cicchetti’s innovative work). The current review focuses on future directions for unpredictability research, including probing intergenerational effects, the role of predictability in resilience, cultural and contextual considerations, and novel developmental outcomes that should be tested in relation to childhood unpredictability. We urge the integration of multidisciplinary perspectives and collaborations into future research on unpredictability. We also provide ideas for translating this research to real-world practice and policy and encourage high-quality research testing whether incorporating predictability into interventions and policy improves developmental outcomes, which would support further dissemination of these findings.
Modified Senning procedure in a patient with dextrocardia with left atrial isomerism and anomalous systemic venous drainage: a rare case report
Authors: Munshi Sayar Kumar , Jones Caroline , Dhannapuneni Ramana
Published: March 2024

The atrial switch procedure by Senning or Mustard technique primarily aims in correcting parallel systemic and pulmonary circulations at atrial level. This procedure may be used in late presenting D-transposition of great arteries with a deconditioned left ventricle, congenitally corrected transposition of great arteries and isolated ventricular inversion. We describe the case of a child with dextrocardia, left atrial isomerism with complex pulmonary and systemic venous drainage resulting in mixing at atrial level. She was successfully operated by modified Senning procedure performed through the left-sided atrium.
Ionospheric TEC Prediction Based on Ensemble Learning Models
Authors: Zhou Yang , Liu Jing , Li Shuhan , Li Qiaoling
Published: March 2024

In this paper, we propose the usage of an ensemble learning approach for predicting total electron content (TEC). The training data set spans from 2007 to 2016, while the testing data set is set to the year 2017. The model inputs in our study included Solar radio flux (F107), Solar Wind plasma speed, By, Bz, Dst, Ap, AE, day of year, universal time, 30‐day and 90‐day TEC averages. Specifically, eXtreme Gradient Boosting (XGBoost), Gradient Boosting Decision Tree, and Decision Tree were utilized for 1‐hr TEC prediction at high‐ (80°W, 80°N), mid‐ (80°W, 40°N), and low‐ latitudes (80°W, 10°N). Results indicate that all three models performed well in predicting TEC, with a mean error of only approximately 0.6 TECU at high‐ and mid‐ latitudes and 1.13 TECU at low latitudes. At the same time, we compared the model with 1‐day Beijing University of Aeronautics and Astronautics model during the period of magnetic storm from 25 August 2018 to 27 August 2018 and a quiet period from 13 December 2018 to 15 December 2018. In the magnetic storm period, Our model showed an average reduction of 1.83 TECU compared to BUAA model. During the quiet period, XGBoost exhibit an average error that is 1.14 TECU lower than that of BUAA model. Moreover, TEC prediction over the region between the 20°N–45°N and 70°E−120°E during geomagnetic storm has an error of 2.74 TECU, showing the stability and superiority of XGBoost. Overall, the ensemble learning approach exhibits its advantage in predicting TEC.
Intranasal delivery of shRNA to knockdown the 5HT-2A receptor enhances memory and alleviates anxiety
Authors: Rohn Troy T. , Radin Dean , Brandmeyer Tracy , Seidler Peter G. , Linder Barry J. , Lytle Tom , Mee John L. , Macciardi Fabio
Published: March 2024

Short-hairpin RNAs (shRNA), targeting knockdown of specific genes, hold enormous promise for precision-based therapeutics to treat numerous neurodegenerative disorders. However, whether shRNA constructed molecules can modify neuronal circuits underlying certain behaviors has not been explored. We designed shRNA to knockdown the human HTR2A gene in vitro using iPSC-differentiated neurons. Multi-electrode array (MEA) results showed that the knockdown of the 5HT-2A mRNA and receptor protein led to a decrease in spontaneous electrical activity. In vivo, intranasal delivery of AAV9 vectors containing shRNA resulted in a decrease in anxiety-like behavior in mice and a significant improvement in memory in both mice (104%) and rats (92%) compared to vehicle-treated animals. Our demonstration of a non-invasive shRNA delivery platform that can bypass the blood–brain barrier has broad implications for treating numerous neurological mental disorders. Specifically, targeting the HTR2A gene presents a novel therapeutic approach for treating chronic anxiety and age-related cognitive decline.
Mitochondria-associated endoplasmic reticulum membrane (MAM): a dark horse for diabetic cardiomyopathy treatment
Authors: Liu Yong , Huo Jin-Ling , Ren Kaidi , Pan Shaokang , Liu Hengdao , Zheng Yifeng , Chen Jingfang , Qiao Yingjin , Yang Yang , Feng Qi
Published: March 2024

Diabetic cardiomyopathy (DCM), an important complication of diabetes mellitus (DM), is one of the most serious chronic heart diseases and has become a major cause of heart failure worldwide. At present, the pathogenesis of DCM is unclear, and there is still a lack of effective therapeutics. Previous studies have shown that the homeostasis of mitochondria and the endoplasmic reticulum (ER) play a core role in maintaining cardiovascular function, and structural and functional abnormalities in these organelles seriously impact the occurrence and development of various cardiovascular diseases, including DCM. The interplay between mitochondria and the ER is mediated by the mitochondria-associated ER membrane (MAM), which participates in regulating energy metabolism, calcium homeostasis, mitochondrial dynamics, autophagy, ER stress, inflammation, and other cellular processes. Recent studies have proven that MAM is closely related to the initiation and progression of DCM. In this study, we aim to summarize the recent research progress on MAM, elaborate on the key role of MAM in DCM, and discuss the potential of MAM as an important therapeutic target for DCM, thereby providing a theoretical reference for basic and clinical studies of DCM treatment.
Strong positive selection biases identity-by-descent-based inferences of recent demography and population structure in Plasmodium falciparum
Authors: Guo Bing , Borda Victor , Laboulaye Roland , Spring Michele D. , Wojnarski Mariusz , Vesely Brian A. , Silva Joana C. , Waters Norman C. , O’Connor Timothy D. , Takala-Harrison Shannon
Published: March 2024

Malaria genomic surveillance often estimates parasite genetic relatedness using metrics such as Identity-By-Decent (IBD), yet strong positive selection stemming from antimalarial drug resistance or other interventions may bias IBD-based estimates. In this study, we use simulations, a true IBD inference algorithm, and empirical data sets from different malaria transmission settings to investigate the extent of this bias and explore potential correction strategies. We analyze whole genome sequence data generated from 640 new and 3089 publicly available Plasmodium falciparum clinical isolates. We demonstrate that positive selection distorts IBD distributions, leading to underestimated effective population size and blurred population structure. Additionally, we discover that the removal of IBD peak regions partially restores the accuracy of IBD-based inferences, with this effect contingent on the population’s background genetic relatedness and extent of inbreeding. Consequently, we advocate for selection correction for parasite populations undergoing strong, recent positive selection, particularly in high malaria transmission settings.
Expression of ALS-PFN1 impairs vesicular degradation in iPSC-derived microglia
Authors: Funes Salome , Jung Jonathan , Gadd Del Hayden , Mosqueda Michelle , Zhong Jianjun , Shankaracharya  , Unger Matthew , Stallworth Karly , Cameron Debra , Rotunno Melissa S. , Dawes Pepper , Fowler-Magaw Megan , Keagle Pamela J. , McDonough Justin A. , Boopathy Sivakumar , Sena-Esteves Miguel , Nickerson Jeffrey A. , Lutz Cathleen , Skarnes William C. , Lim Elaine T. , Schafer Dorothy P. , Massi Francesca , Landers John E. , Bosco Daryl A.
Published: March 2024

Microglia play a pivotal role in neurodegenerative disease pathogenesis, but the mechanisms underlying microglia dysfunction and toxicity remain to be elucidated. To investigate the effect of neurodegenerative disease-linked genes on the intrinsic properties of microglia, we studied microglia-like cells derived from human induced pluripotent stem cells (iPSCs), termed iMGs, harboring mutations in profilin-1 (PFN1) that are causative for amyotrophic lateral sclerosis (ALS). ALS-PFN1 iMGs exhibited evidence of lipid dysmetabolism, autophagy dysregulation and deficient phagocytosis, a canonical microglia function. Mutant PFN1 also displayed enhanced binding affinity for PI3P, a critical signaling molecule involved in autophagic and endocytic processing. Our cumulative data implicate a gain-of-toxic function for mutant PFN1 within the autophagic and endo-lysosomal pathways, as administration of rapamycin rescued phagocytic dysfunction in ALS-PFN1 iMGs. These outcomes demonstrate the utility of iMGs for neurodegenerative disease research and implicate microglial vesicular degradation pathways in the pathogenesis of these disorders.
Artificial cells for in vivo biomedical applications through red blood cell biomimicry
Authors: Waeterschoot Jorik , Gosselé Willemien , Lemež Špela , Casadevall i Solvas Xavier
Published: March 2024

Recent research in artificial cell production holds promise for the development of delivery agents with therapeutic effects akin to real cells. To succeed in these applications, these systems need to survive the circulatory conditions. In this review we present strategies that, inspired by the endurance of red blood cells, have enhanced the viability of large, cell-like vehicles for in vivo therapeutic use, particularly focusing on giant unilamellar vesicles. Insights from red blood cells can guide modifications that could transform these platforms into advanced drug delivery vehicles, showcasing biomimicry’s potential in shaping the future of therapeutic applications.
Elevation-dependent pattern of net CO2 uptake across China
Authors: Wei Da , Tao Jing , Wang Zhuangzhuang , Zhao Hui , Zhao Wei , Wang Xiaodan
Published: March 2024

The elevation gradient has long been known to be vital in shaping the structure and function of terrestrial ecosystems, but little is known about the elevation-dependent pattern of net CO2 uptake, denoted by net ecosystem productivity (NEP). Here, by analyzing data from 203 eddy covariance sites across China, we report a negative linear elevation-dependent pattern of NEP, collectively shaped by varying hydrothermal factors, nutrient supply, and ecosystem types. Furthermore, the NEP shows a higher temperature sensitivity in high-elevation environments (3000–5000 m) compared with the lower-elevation environments (<3000 m). Model ensemble and satellite-based observations consistently reveal more rapid relative changes in NEP in high-elevation environments during the last four decades. Machine learning also predicts a stronger relative increase in high-elevation environments, whereas less change is expected at lower elevations. We therefore conclude a varying elevation-dependent pattern of the NEP of terrestrial ecosystems in China, although there is significant uncertainty involved.
Metabolic profiles outperform the microbiota in assessing the response of vaginal microenvironments to the changed state of HPV infection
Authors: Dai Wenkui , Du Hui , Zhou Qian , Li Sumei , Wang Yinan , Hou Jun , Guo Chunlei , Yang Qing , Li Changzhong , Xie Shouxia , Li Shuai Cheng , Wu Ruifang
Published: March 2024

There is a deficiency in population-based studies investigating the impact of HPV infection on vaginal microenvironment, which influences the risk of persistent HPV infection. This prospective study aimed to unravel the dynamics of vaginal microbiota (VM) and vaginal metabolome in reaction to the changed state of HPV infection. Our results propose that the vaginal metabolome may be a superior indicator to VM when assessing the impact of altered HPV state on the vaginal microenvironment.
Reporting on invasive lobular breast cancer in clinical trials: a systematic review
Authors: Van Baelen Karen , Van Cauwenberge Josephine , Maetens Marion , Beck Gabriela , Camden Ann , Chase Megan-Claire , Fraser Valerie , Freeney Siobhan , Hutcheson Laurie , Levine Julia K. , Lien Tone , Terveer Rian , Turner Claire , Senkus Elzbieta , Jankowitz Rachel C. , Vandecaveye Vincent , Floris Giuseppe , Neven Patrick , Wildiers Hans , Sawyer Elinor , Vincent-Salomon Anne , Derksen Patrick W. B. , Desmedt Christine
Published: March 2024

Invasive lobular breast cancer (ILC) differs from invasive breast cancer of no special type in many ways. Evidence on treatment efficacy for ILC is, however, lacking. We studied the degree of documentation and representation of ILC in phase III/IV clinical trials for novel breast cancer treatments. Trials were identified on Pubmed and clinicaltrials.gov. Inclusion/exclusion criteria were reviewed for requirements on histological subtype and tumor measurability. Documentation of ILC was assessed and ILC inclusion rate, central pathology and subgroup analyses were evaluated. Inclusion restrictions concerning tumor measurability were found in 39/93 manuscripts. Inclusion rates for ILC were documented in 13/93 manuscripts and varied between 2.0 and 26.0%. No central pathology for ILC was reported and 3/13 manuscripts had ILC sub-analyses. ILC is largely disregarded in most trials with poor representation and documentation. The current inclusion criteria using RECIST v1.1, fall short in recognizing the unique non-measurable metastatic infiltration of ILC.
Cryogenic propellant management in space: open challenges and perspectives
Authors: Simonini Alessia , Dreyer Michael , Urbano Annafederica , Sanfedino Francesco , Himeno Takehiro , Behruzi Philipp , Avila Marc , Pinho Jorge , Peveroni Laura , Gouriet Jean-Baptiste
Published: March 2024

This paper presents open challenges and perspectives of propellant management for crewed deep space exploration. The most promising propellants are liquid hydrogen and liquid methane, together with liquid oxygen as an oxidizer. These fluids remain liquid only at cryogenic conditions, that is, at temperatures lower than 120 K. To extend the duration of space exploration missions, or even to enable them, the storage and refueling from a cryogenic on-orbit depot is necessary. We review reference missions, architectures, and technology demonstrators and explain the main operations that are considered as enablers for cryogenic storage and transfer. We summarize the state of the art for each of them, showing that many gaps in physical knowledge still need to be filled. This paper is based on recommendations originally proposed in a White Paper for ESA’s SciSpacE strategy.
Performance of castor oil polyurethane resin in composite with the piassava fibers residue from the Amazon
Authors: Rabelo Aparício Rosinaldo , Machado dos Santos Gabrielle , Siqueira Magalhães Rebelo Viviane , Mansanares Giacon Virgínia , Gomes da Silva Cristina
Published: March 2024

The use of castor oil in producing polyurethane resins has been identified as one of the most promising options for the industry. The piassava fibers waste generated by the industry on a large scale presents excellent properties as a reinforcing agent due to its high lignin content characterized by chemical tests and FTIR. Composite boards consisting of a higher content of mercerized piassava fibers (10 mm, 85 wt.%) reinforced polyurethane castor oil-based resin (prepolymer (PP) and polyol (OM)) exhibited excellent performance. Composites with these properties have strong potential for medium-density applications ranging from biomedical prosthetics to civil partition walls and insulation linings. Alkali treatment removed the superficial impurities of piassava fibers, activating polar groups, and physical characterization reported excellent performance for all composites. Among the composites, the CP3 sample (composite reinforced with piassava fibers (85 wt.% fibers; 1.2:1—PP:OM)) stood out with higher density and lower swelling and water absorption percentage than other composites. FTIR results indicated NCO traces after the resin cured in the PU3 (1.2:1—PP:OM), possibly contributing to the interaction with the fibers. DMA results reported relevant information about more flexibility to CP1 (composite reinforced with piassava fibers (85 wt.% fibers; 0.8:1—PP:OM)) and CP3 than CP2 (composite reinforced with piassava fibers (85 wt.% fibers; 1:1—PP:OM)). The results suggest that the proper combination with natural products must lead to composites with potential applications as engineering materials.
Comparison of mortality and outcomes of four respiratory viruses in the intensive care unit: a multicenter retrospective study
Authors: Grangier Baptiste , Vacheron Charles-Hervé , De Marignan Donatien , Casalegno Jean-Sebastien , Couray-Targe Sandrine , Bestion Audrey , Ader Florence , Richard Jean-Christophe , Frobert Emilie , Argaud Laurent , Rimmele Thomas , Lukaszewicz Anne-Claire , Aubrun Frédéric , Dailler Frédéric , Fellahi Jean-Luc , Bohe Julien , Piriou Vincent , Allaouchiche Bernard , Friggeri Arnaud , Wallet Florent ,   The Lyon Sud COVID-19 ICU, Thiolliere Fabrice , Joffredo Emilie , Jay Lucille , Darien Marie , David Jean-Stéphane , Cerruti Charlotte , Lecocq Maxime , Izaute Guillaume , Collenot Thomas , Vassal Olivia
Published: March 2024

This retrospective study aimed to compare the mortality and burden of respiratory syncytial virus (RSV group), SARS-CoV-2 (COVID-19 group), non-H1N1 (Seasonal influenza group) and H1N1 influenza (H1N1 group) in adult patients admitted to intensive care unit (ICU) with respiratory failure. A total of 807 patients were included. Mortality was compared between the four following groups: RSV, COVID-19, seasonal influenza, and H1N1 groups. Patients in the RSV group had significantly more comorbidities than the other patients. At admission, patients in the COVID-19 group were significantly less severe than the others according to the simplified acute physiology score-2 (SAPS-II) and sepsis-related organ failure assessment (SOFA) scores. Using competing risk regression, COVID-19 (sHR = 1.61; 95% CI 1.10; 2.36) and H1N1 (sHR = 1.87; 95% CI 1.20; 2.93) were associated with a statistically significant higher mortality while seasonal influenza was not (sHR = 0.93; 95% CI 0.65; 1.31), when compared to RSV. Despite occurring in more severe patients, RSV and seasonal influenza group appear to be associated with a more favorable outcome than COVID-19 and H1N1 groups.
Association between oral and fecal microbiome dysbiosis and treatment complications in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation
Authors: Faraci M. , Bonaretti C. , Dell’Orso G. , Pierri F. , Giardino S. , Angiero F. , Blasi S. , Farronato G. , Di Marco E. , Trevisiol A. , Olcese E. , Rufino L. , Squillario M. , Biassoni R.
Published: March 2024

The oral and gastrointestinal mucosae represent the main targets of the toxic effect of chemo and/or radiotherapy administered during the conditioning regimen before hematopoietic stem cell transplant (HSCT). These harmful consequences and the immunological complications that may occur after the transplant (such as Graft versus Host Disease, GvHD) are responsible for the clinical symptoms associated with mucositis during the aplasia phase, like pain, nausea, vomiting, and diarrhea. These toxicities could play a critical role in the oral and gastrointestinal microbiomes during the post-transplant phase, and the degree of microbial dysbiosis and dysregulation among different bacterial species could also be crucial in intestinal mucosa homeostasis, altering the host’s innate and adaptive immune responses and favoring abnormal immune responses responsible for the occurrence of GvHD. This prospective pediatric study aims to analyze longitudinally oral and gut microbiomes in 17 pediatric patients who received allogeneic HSCT for malignant and non-malignant diseases. The oral mucositis was mainly associated with an increased relative abundance of Fusobacteria, and Prevotella species, while Streptococcus descendants showed a negative correlation. The fecal microbiome of subjects affected by cutaneous acute GvHD (aGvHD) correlated with Proteobacteria. Oral mucosal microbiota undergoes changes after HSCT, Fusobacteria, and Prevotella represent bacterial species associated with mucositis and they could be the target for future therapeutic approaches, while fecal microbiome in patients with acute GvHD (aGvHD) revealed an increase of different class of Proteobacteria (Alphaproteobacteria and Deltaproteobacteria) and a negative correlation with the class of Gammaproteobacteria.
7-day patterns in Black-White segregation in 49 metropolitan areas
Authors: Chae Joanna
Published: March 2024

While residential segregation is a persistent attribute of metropolitan areas, recent studies find segregation levels fluctuate throughout the day, reaching their lowest levels during daytime hours. This paper shows hourly variations in Black-White segregation from Monday through Sunday for the top 49 most populated metropolitan areas with Global Positioning System (GPS) data collected from mobile phones from October 2018. I find that segregation levels are higher on average over weekends compared to that of weekdays. I use models to identify the characteristics of neighborhoods with higher levels of segregation on weekends, which include all demographic variables and nearly a third of 35 sectors of businesses and organizations, such as retail, personal care, and religious organizations. I also find more than a third of the sectors are associated with higher levels of segregation during business hours on weekdays, including academic institutions, health care, manufacturing, and financial institutions. Findings from this paper display the significance in the distinction between weekdays and weekends with where people spend their time and how this relates to racial segregation. Specifically, Black people, on average, stay in their home census tracts and visit non-White neighborhoods for organizational resources more so than White people. Significant patterns of associations between racial segregation and the majority of businesses demonstrate the salience of race for more industries than previously understood.
Performance of probable dementia classification in a European multi-country survey
Authors: Klee Matthias , Langa Kenneth M. , Leist Anja K.
Published: March 2024

Feasibility constraints limit availability of validated cognitive assessments in observational studies. Algorithm-based identification of ‘probable dementia’ is thus needed, but no algorithm developed so far has been applied in the European context. The present study sought to explore the usefulness of the Langa–Weir (LW) algorithm to detect ‘probable dementia’ while accounting for country-level variation in prevalence and potential underreporting of dementia. Data from 56 622 respondents of the Survey of Health, Ageing and Retirement in Europe (SHARE, 2017) aged 60 years and older with non-missing data were analyzed. Performance of LW was compared to a logistic regression, random forest and XGBoost classifier. Population-level ‘probable dementia’ prevalence was compared to estimates based on data from the Organisation for Economic Co-operation and Development. As such, application of the prevalence-specific LW algorithm, based on recall and limitations in instrumental activities of daily living, reduced underreporting from 61.0 (95% CI, 53.3–68.7%) to 30.4% (95% CI, 19.3–41.4%), outperforming tested machine learning algorithms. Performance in other domains of health and cognitive function was similar for participants classified ‘probable dementia’ and those self-reporting physician-diagnosis of dementia. Dementia classification algorithms can be adapted to cross-national cohort surveys such as SHARE and help reduce underreporting of dementia with a minimal predictor set.
Real-world comparison of terlipressin vs. octreotide as an adjuvant treatment in the management of variceal bleeding
Authors: Rehman H. , Rehman S. T. , Zulfiqar S. , Awan S. , Abid Shahab
Published: March 2024

Variceal bleeding is a major complication and the leading cause of death in patients with cirrhosis and portal hypertension. This study aims to compare the efficacy and safety of terlipressin vs octreotide as an adjuvant to endoscopic management of patients with esophageal variceal bleeding in a real-time scenario. We reviewed the medical records of patients with esophageal variceal bleeding from January 2005 to December 2020 at our tertiary care Aga Khan University Hospital. Mortality was assessed after 6 weeks. A total of 842 patients with variceal bleed were evaluated. 624 patients (74.1%) and 218 patients (25.9%) received Terlipressin and Octreotide respectively. On multiple regression analysis, cardiac events during hospital stay (OR: 11.22), presence of Porto-systemic encephalopathy (OR: 3.79), and elevated bilirubin levels at the time of presentation were found to be independent risk factors for increased six weeks mortality. Moreover, cardiac events during hospital stay (OR: 3.26), Porto-systemic encephalopathy at presentation (OR: 3.06), and octreotide administration (OR: 1.80) were identified as independent risk factors for increased length of hospital stay. Terlipressin and Octreotide have similar outcomes in terms of control of bleeding, hospital stay, mortality, and side effects when used as adjuvant therapy for the management of variceal bleeding.
Development of a novel AAK1 inhibitor via Kinobeads-based screening
Authors: Yoshida Akari , Ohtsuka Satomi , Matsumoto Fumiya , Miyagawa Tomoyuki , Okino Rei , Ikeda Yumeya , Tada Natsume , Gotoh Akira , Magari Masaki , Hatano Naoya , Morishita Ryo , Satoh Ayano , Sunatsuki Yukinari , Nilsson Ulf J. , Ishikawa Teruhiko , Tokumitsu Hiroshi
Published: March 2024

A chemical proteomics approach using Ca2+/calmodulin-dependent protein kinase kinase (CaMKK) inhibitor–immobilized sepharose (TIM-063-Kinobeads) identified main targets such as CaMKKα/1 and β/2, and potential off-target kinases, including AP2-associated protein kinase 1 (AAK1), as TIM-063 interactants. Because TIM-063 interacted with the AAK1 catalytic domain and inhibited its enzymatic activity moderately (IC50 = 8.51 µM), we attempted to identify potential AAK1 inhibitors from TIM-063-derivatives and found a novel AAK1 inhibitor, TIM-098a (11-amino-2-hydroxy-7H-benzo[de]benzo[4,5]imidazo[2,1-a]isoquinolin-7-one) which is more potent (IC50 = 0.24 µM) than TIM-063 without any inhibitory activity against CaMKK isoforms and a relative AAK1-selectivity among the Numb-associated kinases family. TIM-098a could inhibit AAK1 activity in transfected cultured cells (IC50 = 0.87 µM), indicating cell-membrane permeability of the compound. Overexpression of AAK1 in HeLa cells significantly reduced the number of early endosomes, which was blocked by treatment with 10 µM TIM-098a. These results indicate TIM-063-Kinobeads-based chemical proteomics is efficient for identifying off-target kinases and re-evaluating the kinase inhibitor (TIM-063), leading to the successful development of a novel inhibitory compound (TIM-098a) for AAK1, which could be a molecular probe for AAK1. TIM-098a may be a promising lead compound for a more potent, selective and therapeutically useful AAK1 inhibitor.
Bone marrow-derived mesenchymal stem cells mitigate chronic colitis and enteric neuropathy via anti-inflammatory and anti-oxidative mechanisms
Authors: Stavely Rhian , Robinson Ainsley M. , Fraser Sarah , Filippone Rhiannon T. , Stojanovska Vanesa , Eri Rajaraman , Apostolopoulos Vasso , Sakkal Samy , Nurgali Kulmira
Published: March 2024

Current treatments for inflammatory bowel disease (IBD) are often inadequate due to limited efficacy and toxicity, leading to surgical resection in refractory cases. IBD’s broad and complex pathogenesis involving the immune system, enteric nervous system, microbiome, and oxidative stress requires more effective therapeutic strategies. In this study, we investigated the therapeutic potential of bone marrow-derived mesenchymal stem cell (BM-MSC) treatments in spontaneous chronic colitis using the Winnie mouse model which closely replicates the presentation and inflammatory profile of ulcerative colitis. The 14-day BM-MSC treatment regimen reduced the severity of colitis, leading to the attenuation of diarrheal symptoms and recovery in body mass. Morphological and histological abnormalities in the colon were also alleviated. Transcriptomic analysis demonstrated that BM-MSC treatment led to alterations in gene expression profiles primarily downregulating genes related to inflammation, including pro-inflammatory cytokines, chemokines and other biomarkers of inflammation. Further evaluation of immune cell populations using immunohistochemistry revealed a reduction in leukocyte infiltration upon BM-MSC treatment. Notably, enteric neuronal gene signatures were the most impacted by BM-MSC treatment, which correlated with the restoration of neuronal density in the myenteric ganglia. Moreover, BM-MSCs exhibited neuroprotective effects against oxidative stress-induced neuronal loss through antioxidant mechanisms, including the reduction of mitochondrial-derived superoxide and attenuation of oxidative stress-induced HMGB1 translocation, potentially relying on MSC-derived SOD1. These findings suggest that BM-MSCs hold promise as a therapeutic intervention to mitigate chronic colitis by exerting anti-inflammatory effects and protecting the enteric nervous system from oxidative stress-induced damage.
Multi-hop clustering routing protocol design based on simultaneous wireless information and power transfer technology and imperfect spectrum sensing for EH-CRSNs
Authors: Wang Jihong , Xie Zixiao , Liu Chang
Published: March 2024

Existing clustering routing protocols for multi-hop energy harvesting-cognitive radio sensor networks (EH-CRSNs) generally assume perfect spectrum sensing, which is not aligned with the practical spectrum sensing capabilities of nodes in real networks. Additionally, the severe imbalance in residual energy among cluster heads (CHs) negatively affects the successful data delivery. To resolve these problems, this paper introduces a simultaneous wireless information and power transfer (SWIPT)- and imperfect spectrum sensing-based multi-hop clustering routing protocol (ES-ISSMCRP). ES-ISSMCRP makes full use of downlink EH and intra-cluster SWIPT technologies to replenish and equalize the remaining energy among nodes, further extending network lifespan while maintaining network surveillance capabilities. Specifically, to reduce the adverse impact of imperfect spectrum sensing on network performance and improve energy utilization, this paper proposes an EH-based energy level function and associated selection criteria for CHs and relays, facilitating distributed cluster formation and multi-hop routing selection between clusters. To equalize the residual energy among nodes within a cluster, ES-ISSMCRP protocol enables cluster members (CMs) to decide whether employ SWIPT technology with a power splitting (PS) receiver architecture to transmit energy to their CH while sending data. The actual energy value transmitted by CMs using SWIPT technology is deduced by calculating the PS ratio and the expected energy expenditure of nodes for data transmission. Simulation results show that ES-ISSMCRP protocol offers significant improvements over other comparative protocols in terms of extending network lifespan and enhancing network surveillance capabilities.
Air pollution exposure may impact the composition of human milk oligosaccharides
Authors: Naik Noopur C. , Holzhausen Elizabeth A. , Chalifour Bridget N. , Coffman Maria M. , Lurmann Fredrick , Goran Michael I. , Bode Lars , Alderete Tanya L.
Published: March 2024

Human milk oligosaccharides (HMOs) impact neonate immunity and health outcomes. However, the environmental factors influencing HMO composition remain understudied. This study examined the associations between ambient air pollutant (AAP) exposure and HMOs at 1-month postpartum. Human milk samples were collected at 1-month postpartum (n = 185). AAP (PM2.5, PM10, NO2) exposure included the 9-month pregnancy period through 1-month postpartum. Associations between AAP with (1) HMO diversity, (2) the sum of sialylated and fucosylated HMOs, (3) 6 a priori HMOs linked with infant health, and (4) all HMOs were examined using multivariable linear regression and principal component analysis (PCA). Exposure to AAP was associated with lower HMO diversity. PM2.5 and PM10 exposure was positively associated with the HMO 3-fucosyllactose (3FL); PM2.5 exposure was positively associated with the sum of total HMOs, sum of fucosylated HMOs, and the HMO 2′-fucosyllactose (2′FL). PCA indicated the PM2.5, PM10, and NO2 exposures were associated with HMO profiles. Individual models indicated that AAP exposure was associated with five additional HMOs (LNFP I, LNFP II, DFLNT, LNH). This is the first study to demonstrate associations between AAP and breast milk HMOs. Future longitudinal studies will help determine the long-term impact of AAP on human milk composition.
Surface modification and coherence in lithium niobate SAW resonators
Authors: Gruenke Rachel G. , Hitchcock Oliver A. , Wollack E. Alex , Sarabalis Christopher J. , Jankowski Marc , McKenna Timothy P. , Lee Nathan R. , Safavi-Naeini Amir H.
Published: March 2024

Lithium niobate is a promising material for developing quantum acoustic technologies due to its strong piezoelectric effect and availability in the form of crystalline thin films of high quality. However, at radio frequencies and cryogenic temperatures, these resonators are limited by the presence of decoherence and dephasing due to two-level systems. To mitigate these losses and increase device performance, a more detailed picture of the microscopic nature of these loss channels is needed. In this study, we fabricate several lithium niobate acoustic wave resonators and apply different processing steps that modify their surfaces. These treatments include argon ion sputtering, annealing, and acid cleans. We characterize the effects of these treatments using three surface-sensitive measurements: cryogenic microwave spectroscopy measuring density and coupling of TLS to mechanics, X-ray photoelectron spectroscopy and atomic force microscopy. We learn from these studies that, surprisingly, increases of TLS density may accompany apparent improvements in the surface quality as probed by the latter two approaches. Our work outlines the importance that surfaces and fabrication techniques play in altering acoustic resonator coherence, and suggests gaps in our understanding as well as approaches to address them.
Determination of oxidative stress level and some antioxidant activities in refractory epilepsy patients
Authors: Yilgor Abdullah , Demir Canan
Published: March 2024

The aim of this study was to determine the levels of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and malondialdehyde (MDA) in patients with refractory epilepsy. Serum superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and malondialdehyde (MDA) levels were determined using the spectrophotometer method. Refractory epilepsy patients’ serum superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and malondialdehyde (MDA) levels were statistically significant compared to the healthy control group (p < 0.05). In conclusion, superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and malondialdehyde (MDA) levels may play an important role in the etiopathogenesis of refractory epilepsy. This study was the first to investigate some parameters in refractory epilepsy disease.
Depth perception of stereoscopic transparent stimuli with frame manipulation
Authors: Aida Saori , Fukamachi Shunta , Shimono Koichi
Published: March 2024

Depth perception is crucial in human vision, allowing us to move and interact with our 3-D surroundings. We used a stereoscopic transparent stimulus comprising parallel overlapping transparent stereoscopic surfaces (POTS) to understand depth perception better. The study focused on exploring the effect of a surrounding frame on the perceived depth of a POTS configuration. The research was based on a proposed idea that explains an "off-frame" effect: a frame at a different depth from a 2-D photograph depicting a 3-D scene increases its apparent depth qualitatively. The idea assumes that processing the disparity between a frame and a photo reduces the reliability of the photograph's flatness cues and increases depth magnitude in depth cue integration. We examined whether the idea can be applied to a 3-D POTS with the flatness cue as the constant accommodation. Through three experiments, the study showed that frames impact the perceived depth magnitude of a POTS configuration. More specifically, the depth magnitude increases as the frame's disparity concerning the monitor plane increases and decreases as the frame's size increases. We discussed the results in the context of depth cue combination.
Prmt6 represses the pro-adipogenic Ppar-gamma–C/ebp-alpha transcription factor loop
Authors: Gerstner Mirjam , Heller Vivien , Fechner Johannes , Hermann Benedikt , Wang Lei , Lausen Joern
Published: March 2024

The feed-forward loop between the transcription factors Ppar-gamma and C/ebp-alpha is critical for lineage commitment during adipocytic differentiation. Ppar-gamma interacts with epigenetic cofactors to activate C/ebp-alpha and the downstream adipocytic gene expression program. Therefore, knowledge of the epigenetic cofactors associated with Ppar-gamma, is central to understanding adipocyte differentiation in normal differentiation and disease. We found that Prmt6 is present with Ppar-gamma on the Ppar-gamma and C/ebp-alpha promoter. It contributes to the repression of C/ebp-alpha expression, in part through its ability to induce H3R2me2a. During adipocyte differentiation, Prmt6 expression is reduced and the methyltransferase leaves the promoters. As a result, the expression of Ppar-gamma and C/ebp-alpha is upregulated and the adipocytic gene expression program is established. Inhibition of Prmt6 by a small molecule enhances adipogenesis, opening up the possibility of epigenetic manipulation of differentiation. Our data provide detailed information on the molecular mechanism controlling the Ppar-gamma–C/ebp-alpha feed-forward loop. Thus, they advance our understanding of adipogenesis in normal and aberrant adipogenesis.