bluuebunny/crossref_metadata_2025 huggingface dataset:
Community-based irrigation management in Indonesia (Case study: Musi Rawas Regency, Bandung Regency, and Soppeng Regency)
Authors: Abdi A. P. , Ajrina F. I. , Afifah N. Z. , Maryati S.
Published: May 2024

Indonesia is an agricultural country that relies on the food sector.Irrigation infrastructure plays an important role to support the sector. It is therefore the sustainability of irrigation is vital. Community-based management of irrigation has been developed in Indonesia to support the development, operation, and and maintenance of irrigation. The aim of this study is to explore community-based irrigation management to support the sustainability of irrigation infrastructure. Three locations were choosed as case study; Musi Rawas, Bandung, and Soppeng Regency. The data analysis method used is qualitative analysis. The results of this study indicate that community groups are involved in determining irrigation development, such as holding public consultations, site selection, surveys, land acquisition, cooperation, operation, and maintenance. However, this community group does not yet have a robust organizational role because it has not provided rules, sanctions, or solutions to solve problems in the field. In addition, there is a lack of government support for community groups. Realizing a sustainable community-based irrigation system requires a high role of the community in irrigation management and support from the government in supporting the capacity of community groups and financing participatory activities.
Comparative literature review of student preferences and activity patterns on the use of campus open space before and during The Covid-19 Pandemic at the ITB Ganesha Campus
Authors: Firmansyah  , Nidia Kusuma Bintang , Prayuni Rante Allo Ira , Azmi Nur Khalid Fikri , Djasmin Ramadhanty Bunga
Published: May 2024

A campus is a place where students can spend most of their time. There are various activities carried out both academic and non-academic, for self-development and positive socialization. Campus open space is one area that can accommodate these activities. However, the Covid-19 pandemic has had an impact on the loss of various activities on campus. After the effects of the Covid-19 pandemic began to diminish, campus activities have slowly started to becarried out again offline, including activities in campus open spaces. Therefore, it is necessary to review the possibility of changes to preferences and activity patterns in campus open spaces related to the limitations of joint activities as a form of prevention of transmission during the Covid-19 Pandemic. This article would like to review various literature studies related to preferences for the use of open spaces and student activity patterns before the onset of Covid-19, including literature studies related to landscape elements that form spaces that can support student activities in open spaces. This article also reviews the literature on changes in the use of open spaces during the Covid-19 pandemic which was influenced by activity restrictions from the application of strict health protocols.
Enhancing workers’ quality of life: why land use mix should be increased? (Case study: Semarang City)
Authors: Badawi Wempi Suek Jonathan
Published: May 2024

Nowadays, many urban workers are struggling and exhausted because of commuting activity due to the effect of urban sprawl. In order to overcome the externalities of the sprawl, many cities are directed to become more compact, to reduce travel time and cost. The efficiency that comes from the proximity of mixed-use development helps workers allocate time and money for participating in other activities and indirectly increases their quality of life. This article reviews the importance of increasing the land use mix to facilitate workers’ activities. The network and entropy index analyses are used to examine the land use mix in the study area. Then the result is discussed in the context of the travel behavior approach theory. The result shows the aggregate land use mix in the study area is moderate-mix with an index of 0,47. In detail, areas under 2 kilometers have a high mix of land use (0,63-0,74), but the value decreases as it moves away from the city center to an index of 0,4. This study reveals that increasing number of land use variants does not improve the land use mix, but balancing the proportion of land use area is more important to increase the mix. It is necessary to improve land use mix because there are approximately 6.939-13.877 workers in the area that should be facilitated so they might participate in other activities effectively. Workers with a simple trip chain might be facilitated handily. But as the land use mix increases, workers with a complex trip chain might fulfill their needs within the area. Integrating land use and transportation allows workers to make active trips, which can affect their health and quality of life.
Ozone production over arid regions: insights into meteorological and chemical drivers
Authors: Mirrezaei Mohammad Amin , Arellano Avelino , Guo Yafang , Roychoudhury Chayan , Sorooshian Armin
Published: May 2024

Arid urban areas are pivotal in the global landscape, and their air quality issues are highlighted by the complexities of tropospheric ozone production. Here, we use recent satellite observations from TROPOMI and a longer record of data from OMI to investigate the levels of ozone precursors (NO2 and CH2O) in 12 major cities in arid regions. Using a space-based CH2O/NO2 indicator, we identified the dominant chemical regime influencing ozone formation, revealing a clear temporal trend that aligns with previously reported economic trajectories as well as variation in emission control strategies implemented in these cities. Our results show that, NO2 concentrations decreased in cities with proactive regulatory policies, such as Madrid and Los Angeles in semi-arid and arid regions. A contrasting increase was observed in rapidly developing cities within arid and hyper-arid regions, such as Tehran and Cairo, where emission controls are less strict. An increase in CH2O levels was also apparent, requiring more attention to VOCs control. Furthermore, our analysis clearly shows that the interactions between ozone production and climatic factors such as temperature exhibit a nonlinear relationship, especially in arid climates. These findings highlight the importance of emission reduction strategies that consider the meteorological and chemical drivers of dry regions, particularly in light of the rising global aridity.
Emerging environmental justice issues at the intersection of transportation and electricity systems
Authors: Hennessy Eleanor M , Azevedo Inês M L
Published: May 2024

Rapid decarbonization of the transportation system is needed to address global climate change, and electrification of the transportation sector will likely be an important strategy to achieve decarbonization goals. While electrification is an effective approach to reducing carbon emissions, it may result in environmental justice consequences that need to be tackled. We discuss four categories of related issues: air quality and health-related equity; technology access; equitable infrastructure development; and a just global supply chain. In regions where grid decarbonization is well under way, transport-related disparities in air quality and health are expected to decrease with electrification. In contrast, in regions that still rely heavily on coal generation, disparities may increase, putting further strain on low-income communities and people of color. The high upfront cost of electric vehicles and limited access to charging present additional challenges for achieving equity in transportation electrification. Meeting the electricity demand of a fully electric vehicle fleet will require rapid expansion of power generation, transmission, and distribution capacity, and the location and design of this infrastructure will have further impacts on communities where it is sited. Here, we offer a perspective on these emerging environmental justice issues at the intersection of transportation and electricity systems and provide policy recommendations and future research directions for electrified transportation. We suggest there is a need for policies targeting electrification and power sector decarbonization in tandem, assessment of barriers to electric vehicle adoption in different groups, development of strategies for community inclusion in infrastructure development decisions, and creation of frameworks to assess equity tradeoffs along the global supply chain supporting electric vehicles and renewable energy technologies.
Treatment of Orthostatic Hypotension During Acute Inpatient Rehabilitation After Spinal Cord Injury: Usual Care vs. Anti-hypotensive Therapy
Authors: Wecht Jill M , Weir Joseph P , Huang Vincent , Escalon Miguel X , Bryce Thomas N
Published: May 2024

BACKGROUND

To compare the pharmacological treatment of hypotension and orthostatic hypotension (OH) initiated based upon a blood pressure (BP) threshold, regardless of symptoms (TXT), to usual care pharmacological treatment of symptomatic hypotension (UC), during acute inpatient rehabilitation (AIR) following spinal cord injury (SCI).

METHODS

Block randomization, based on the neurological level of injury as: cervical lesions (C1–C8); high thoracic lesions (T1–T5), and low thoracic lesions (T6–T12), was used to determine responses to the primary question “was the therapy session affected by low BP or concern for low BP development?” Study participants and therapists were unaware of the group assignment.

RESULTS

A total of 66 participants enrolled; 25 (38%) in the TXT group, 29 (44%) in the UC group, and 12 (18%) withdrew. Responses to the primary question were recorded for 32 participants, 15 in the TXT, and 17 in the UC group. There was an average of 81 ± 51 therapy sessions/participant in the TXT and 60 ± 27 sessions/participant in the UC group. Of those therapy sessions, low BP or concerns for low BP affected an average of 9 ± 8 sessions/participant in the TXT group and 10 ± 12 sessions/participant in the UC group. Neither the total number of therapy sessions (P = 0.16) nor group assignment (P = 0.83) significantly predicted the number of sessions affected by low BP.

CONCLUSIONS

These data are not conclusive but indicate that the treatment of asymptomatic hypotension and OH does not increase time spent in therapy compared to UC treatment of symptomatic hypotension and OH in newly injured patients with SCI.

CLINICAL TRIALS REGISTRATION

#NCT02919917.
Clinical Utility of the Neuropsychological Assessment Battery Judgment Subtest in the Evaluation of Older Adults
Authors: Donders Jacobus , Maher Tracy
Published: May 2024

Objective

The purpose of this retrospective archival study was to explore the clinical utility of the Judgment subtest of the Neuropsychological Assessment Battery (NAB) in older adults who were referred because of cognitive concerns. Specifically, we were interested in how NAB Judgment covaried with other measures of executive functioning.

Method

226 adults, aged 61–89 years (48% dementia, 35% mild cognitive impairment, 18% cognitively intact) completed NAB Judgment. They also completed Trail Making Test (TMT) A and B. In addition, Behavior Rating Inventory of Executive Function (BRIEF–A) informant and self-reports were obtained to measure executive functioning in daily life.

Results

Scores on NAB Judgment did not correlate significantly with BRIEF–A informant ratings. However, there was a statistically significant correlation between BRIEF–A informant ratings and TMT B. Better performance on TMT B was associated with fewer informant concerns. Furthermore, subgroups with versus without informant BRIEF–A Metacognition indices in the range of impairment demonstrated a statistically significant difference on TMT B but not on Judgment.

Conclusions

Executive functioning in older adults should not be assessed using NAB Judgment alone. Such an evaluation should be supplemented with other in-person tests as well as informant ratings of daily functioning.
The Breast-Pectoralis Flap: A New Advance in Autologous Breast Reconstruction—A Preliminary Report on 20 Cases
Authors: Delay Emmanuel , Michel Gautier , Mambour Gwenola , Meruta Andreea Carmen , Frobert Paul , Perez Simon
Published: May 2024

Background

In the past, several publications have described breast reconstruction techniques that utilize the contralateral breast; however, interest diminished because of technical difficulty, scarring, and poor aesthetic results.

Objectives

This study aimed to present a new breast reconstruction technique that uses a combination of the breast-pectoralis flap and the abdominal advancement flap.

Methods

This retrospective study analyzed the results and complications of 20 consecutive breast reconstructions with the breast-pectoralis flap technique.

Results

The authors present a series of 20 breast reconstructions that utilized the breast-pectoralis flap. Delayed breast reconstruction was performed in 13 cases (65%), breast reconstruction in 5 patients (25%) with Poland syndrome, sequela correction after a chest wall sarcoma in 1 patient (5%), and sequela correction after breast cystic lymphangioma resection in 1 patient (5%). One complication required surgical reintervention without long-term consequences. The outcomes were considered very good in 50% of the cases, good in 45%, and fair in 5%.

Conclusions

The combination of the breast-pectoralis flap and the abdominal advancement flap is an interesting advance in breast reconstruction. Evaluation of the presented cases suggests wider indications for this technique.

Level of Evidence: 4
danRerLib: a Python package for zebrafish transcriptomics
Authors: Schwartz Ashley V , Sant Karilyn E , George Uduak Z
Published: May 2024

Understanding the pathways and biological processes underlying differential gene expression is fundamental for characterizing gene expression changes in response to an experimental condition. Zebrafish, with a transcriptome closely mirroring that of humans, are frequently utilized as a model for human development and disease. However, a challenge arises due to the incomplete annotations of zebrafish pathways and biological processes, with more comprehensive annotations existing in humans. This incompleteness may result in biased functional enrichment findings and loss of knowledge. danRerLib, a versatile Python package for zebrafish transcriptomics researchers, overcomes this challenge and provides a suite of tools to be executed in Python including gene ID mapping, orthology mapping for the zebrafish and human taxonomy, and functional enrichment analysis utilizing the latest updated Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. danRerLib enables functional enrichment analysis for GO and KEGG pathways, even when they lack direct zebrafish annotations through the orthology of human-annotated functional annotations. This approach enables researchers to extend their analysis to a wider range of pathways, elucidating additional mechanisms of interest and greater insight into experimental results.

Availability and implementation

danRerLib, along with comprehensive documentation and tutorials, is freely available. The source code is available at https://github.com/sdsucomptox/danrerlib/ with associated documentation and tutorials at https://sdsucomptox.github.io/danrerlib/. The package has been developed with Python 3.9 and is available for installation on the package management systems PIP (https://pypi.org/project/danrerlib/) and Conda (https://anaconda.org/sdsu_comptox/danrerlib) with additional installation instructions on the documentation website.
Neonicotinoids differentially modulate nicotinic acetylcholine receptors in immature and antral follicles in the mouse ovary
Authors: Mourikes Vasiliki E , Santacruz-Márquez Ramsés , Deviney Ashley , Neff Alison , Laws Mary J , Flaws Jodi A
Published: May 2024

Neonicotinoids are the most widely used insecticides in the world. They are synthetic nicotine derivatives that act as nicotinic acetylcholine receptor agonists. Although parent neonicotinoids have low affinity for the mammalian nicotinic acetylcholine receptor, they can be activated in the environment and the body to positively charged metabolites with high affinity for the mammalian nicotinic acetylcholine receptor. Imidacloprid, the most popular neonicotinoid, and its bioactive metabolite desnitro-imidacloprid differentially interfere with ovarian antral follicle physiology in vitro, but their effects on ovarian nicotinic acetylcholine receptor subunit expression are unknown. Furthermore, ovarian nicotinic acetylcholine receptor subtypes have yet to be characterized in the ovary. Thus, this work tested the hypothesis that ovarian follicles express nicotinic acetylcholine receptors and their expression is differentially modulated by imidacloprid and desnitro-imidacloprid in vitro. We used polymerase chain reaction, RNA in situ hybridization, and immunohistochemistry to identify and localize nicotinic acetylcholine receptor subunits (α2, 4, 5, 6, 7 and β1, 2, 4) expressed in neonatal ovaries (NO) and antral follicles. Chrnb1 was expressed equally in NO and antral follicles. Chrna2 and Chrnb2 expression was higher in antral follicles compared to NO and Chrna4, Chrna5, Chrna6, Chrna7, and Chrnb4 expression was higher in NO compared to antral follicles. The α subunits were detected throughout the ovary, especially in oocytes and granulosa cells. Imidacloprid and desnitro-imidacloprid dysregulated the expression of multiple nicotinic acetylcholine receptor subunits in NO, but only dysregulated one subunit in antral follicles. These data indicate that mammalian ovaries contain nicotinic acetylcholine receptors, and their susceptibility to imidacloprid and desnitro-imidacloprid exposure varies with the stage of follicle maturity.
Estimating brain and eye lens dose for the cardiologist in interventional cardiology—are the dose levels of concern?
Authors: Hulthén Markus , Tsapaki Virginia , Karambatsakidou Angeliki
Published: May 2024

Objectives

To establish conversion coefficients (CCs), between mean absorbed dose to the brain and eye lens of the cardiologist and the air kerma-area product, PKA, for a set of projections in cardiac interventional procedures. Furthermore, by taking clinical data into account, a method to estimate the doses per procedure, or annual dose, is presented.

Methods

Thermoluminescence dosimeters were used together with anthropomorphic phantoms, simulating a cardiologist performing an interventional cardiac procedure, to estimate the CCs for the brain and eye lens dose for nine standard projections, and change in patient size and x-ray spectrum. Additionally, a single CC has been estimated, accounting for each projections fraction of use in the clinic and associated PKA using clinical data from the dose monitoring system in our hospital.

Results

The maximum CCs for the eye lens and segment of the brain, is 5.47 μGy/Gycm2 (left eye lens) and 1.71 μGy/Gycm2 (left brain segment). The corresponding weighted CCs: are 3.39 μGy/Gycm2 and 0.89 μGy/Gycm2, respectively.

Conclusions

Conversion coefficients have been established under actual scatter conditions, showing higher doses on the left side of the operator. Using modern interventional x-ray equipment, interventional cardiac procedures will not cause high radiation dose levels to the operator when a ceiling mounted shield is used, otherwise there is a risk that the threshold dose values for cataract will be reached.

Advance in knowledge

In addition to the CCs for the different projections, methods for deriving a single CC per cardiac interventional procedure and dose per year were introduced.
Randomized clinical trial on D2 lymphadenectomy versus D2 lymphadenectomy plus complete mesogastric excision in patients undergoing gastrectomy for cancer (DCGC01 study)
Authors: Xie Daxing , Shen Jie , Liu Liang , Cao Beibei , Xiao Aitang , Qin Jichao , Wu Jianhong , Yan Qun , Hu Yuanlong , Yang Chuanyong , Cao Zhixin , Hu Junbo , Yin Ping , Gong Jianping
Published: May 2024

Background

It is unknown whether D2 lymphadenectomy + complete mesogastric excision for gastric cancer improves survival compared with just D2 lymphadenectomy.

Methods

Between September 2014 and June 2018, patients with advanced gastric cancer were randomly assigned (1 : 1) to laparoscopic D2 lymphadenectomy or D2 lymphadenectomy + complete mesogastric excision gastrectomy. The modified intention-to-treat population was defined as patients who had pathologically confirmed gastric adenocarcinoma (pT1 N1–3 M0 and pT2–4 N0–3 M0). The primary endpoint was 3-year disease-free survival. Secondary endpoints were the recurrence pattern and overall survival.

Results

The median follow-up of patients in the D2 lymphadenectomy group (169 patients) and patients in the D2 lymphadenectomy +complete mesogastric excision group (169 patients) was 55 (interquartile range 37–60) months and 51 (interquartile range 40–60) months respectively. Recurrence occurred in 50 patients in the D2 lymphadenectomy group (29.6%) versus 33 patients in the D2 lymphadenectomy + complete mesogastric excision group (19.5%) (P = 0.032). The 3-year disease-free survival was 75.5% (95% c.i. 68.3% to 81.3%) in the D2 lymphadenectomy group versus 85.0% (95% c.i. 78.7% to 89.6%) in the D2 lymphadenectomy + complete mesogastric excision group (log rank P = 0.042). The HR for recurrence in the D2 lymphadenectomy + complete mesogastric excision group versus the D2 lymphadenectomy group was 0.64 (95% c.i. 0.41 to 0.99) by Cox regression (P = 0.045). The 3-year overall survival rate was 77.5% (95% c.i. 70.4% to 83.1%) in the D2 lymphadenectomy group versus 85.8% (95% c.i. 79.6% to 90.2%) in the D2 lymphadenectomy + complete mesogastric excision group (log rank P = 0.058). The HR for death in the D2 lymphadenectomy + complete mesogastric excision group versus the D2 lymphadenectomy group was 0.64 (95% c.i. 0.41 to 1.02) (P = 0.058).

Conclusion

Compared with conventional D2 dissection, D2 lymphadenectomy + complete mesogastric excision is associated with better disease-free survival, but there is no statistically significant difference in overall survival.

Registration number

NCT01978444 (http://www.clinicaltrials.gov).
Gallstones as a cause in presumed acute alcoholic pancreatitis: observational multicentre study
Authors: Sissingh Noor J , de Rijk Fleur E M , Timmerhuis Hester C , Umans Devica S , Anten Marie-Paule G F , Bouwense Stefan A W , van Delft Foke , van Eijck Brechje C , Erkelens Willemien G , Hazen Wouter L , Kuiken Sjoerd D , Quispel Rutger , Romkens Tessa E H , Schwartz Matthijs P , Seerden Tom C , Spanier B W Marcel , Verlaan Tessa , Vleggaar Frank P , Voermans Rogier P , Verdonk Robert C , van Hooft Jeanin E
Published: May 2024

Background

Data on the incidence and clinical relevance of gallstones in patients with suspected acute alcoholic pancreatitis are lacking and are essential to minimize the risk of recurrent acute pancreatitis. The aim of this study was to assess the incidence of gallstones and the associated rate of recurrent acute pancreatitis in patients with presumed acute alcoholic pancreatitis.

Methods

Between 2008 and 2019, 23 hospitals prospectively enrolled patients with acute pancreatitis. Those diagnosed with their first episode of presumed acute alcoholic pancreatitis were included in this study. The term gallstones was used to describe the presence of cholelithiasis or biliary sludge found during imaging. The primary outcome was pancreatitis recurrence during 3 years of follow-up.

Results

A total of 334 patients were eligible for inclusion, of whom 316 were included in the follow-up analysis. Gallstone evaluation, either during the index admission or during follow-up, was performed for 306 of 334 patients (91.6%). Gallstones were detected in 54 patients (17.6%), with a median time to detection of 6 (interquartile range 0–42) weeks. During follow-up, recurrent acute pancreatitis occurred in 121 of 316 patients (38.3%), with a significantly higher incidence rate for patients with gallstones compared with patients without gallstones (59% versus 34.2% respectively; P < 0.001), while more patients with gallstones had stopped drinking alcohol at the time of their first recurrence (41% versus 24% respectively; P = 0.020). Cholecystectomy was performed for 19 patients with gallstones (36%). The recurrence rate was lower for patients in the cholecystectomy group compared with patients who did receive inadequate treatment or no treatment (5/19 versus 19/34 respectively; P = 0.038).

Conclusion

Gallstones were found in almost one in every five patients diagnosed with acute alcoholic pancreatitis. Gallstones were associated with a higher rate of recurrent pancreatitis, while undergoing cholecystectomy was associated with a reduction in this rate.
The weed, asbestos pipe and disposable tree: unmuting multispecies Flemish and Norwegian circular site stories for diverse circular economies
Authors: Wuyts Wendy
Published: May 2024

This study explores diverse circular economies and methods of multispecies ethnography in Vorselaar, Belgium and Røros, Norway, to identify care-full justice in small-scale places and to challenge traditional anthropocentric and capitalocentric models. This study unearths circular site stories in Vorselaar’s community-driven sustainability practices and Røros’s integration of cultural heritage in its sustainability approach, highlighting the need for a broader, care-centric perspective in circular economy discourse. The results demonstrate the universality and adaptability of diverse circular economies in fostering narratives of multispecies justice and the need for emphasising multispecies justice and bioregionalism to foster biodiversity, human wellbeing and their need for belonging and ecological citizenship.
Determination of Clinically Acceptable Analytical Variation of Cardiac Troponin at Decision Thresholds
Authors: Pickering John W , Kavsak Peter , Christenson Robert H , Troughton Richard W , Pemberton Christopher J , Richards A Mark , Joyce Laura , Than Martin P
Published: May 2024

Background

Clinical decision-making for risk stratification for possible myocardial infarction (MI) uses high-sensitivity cardiac troponin (hs-cTn) thresholds that range from the limit of detection to several-fold higher than the upper reference limit (URL). To establish a minimum analytical variation standard, we can quantify the effect of variation on the population clinical measures of safety (sensitivity) and effectiveness [proportion below threshold, or positive predictive value (PPV)].

Methods

From large datasets of patients investigated for possible MI with the Abbott hs-cTnI and Roche hs-cTnT assays, we synthesized datasets of 1 000 000 simulated patients. Troponin concentrations were randomly varied several times based on absolute deviations of 0.5 to 3 ng/L and relative changes of 2% to 20% around the low-risk threshold (5 ng/L) and URLs, respectively.

Results

For both assays at the low-risk thresholds, there were negligible differences in sensitivity (<0.3%) with increasing analytical variation. The proportion of patients characterized as low risk reduced by 30% to 29% (Roche) and 53% to 44% (Abbott). At the URL, increasing analytical variation also did not change sensitivity; the PPV fell by less than 3%. For risk stratification, increased delta thresholds (change between serial troponin concentrations) increased sensitivity at the cost of a decreased percentage of patients below the delta threshold, with the largest changes at the greatest analytical variation.

Conclusions

At the low-risk threshold, analytical variation up to 3 ng/L minimally impacted the safety metric (sensitivity) but marginally reduced effectiveness. Similarly, at the URL even relative variation up to 25% minimally impacted safety metrics and effectiveness. Analytical variation for delta thresholds did not negatively impact sensitivity but decreased effectiveness.
FLT4 causes developmental disorders of the cardiovascular and lymphovascular systems via pleiotropic molecular mechanisms
Authors: Monaghan Richard M , Naylor Richard W , Flatman Daisy , Kasher Paul R , Williams Simon G , Keavney Bernard D
Published: May 2024

Aims

Rare, deleterious genetic variants in FLT4 are associated with Tetralogy of Fallot (TOF), the most common cyanotic congenital heart disease. The distinct genetic variants in FLT4 are also an established cause of Milroy disease, the most prevalent form of primary hereditary lymphoedema. The phenotypic features of these two conditions are non-overlapping, implying pleiotropic cellular mechanisms during development.

Methods and results

In this study, we show that FLT4 variants identified in patients with TOF, when expressed in primary human endothelial cells, cause aggregation of FLT4 protein in the perinuclear endoplasmic reticulum, activating proteostatic and metabolic signalling, whereas lymphoedema-associated FLT4 variants and wild-type (WT) FLT4 do not. FLT4 TOF variants display characteristic gene expression profiles in key developmental signalling pathways, revealing a role for FLT4 in cardiogenesis distinct from its role in lymphatic development. Inhibition of proteostatic signalling abrogates these effects, identifying potential avenues for therapeutic intervention. Depletion of flt4 in zebrafish caused cardiac phenotypes of reduced heart size and altered heart looping. These phenotypes were rescued with coinjection of WT human FLT4 mRNA, but incompletely or not at all by mRNA harbouring FLT4 TOF variants.

Conclusion

Taken together, we identify a pathogenic mechanism for FLT4 variants predisposing to TOF that is distinct from the known dominant negative mechanism of Milroy-causative variants. FLT4 variants give rise to conditions of the two circulatory subdivisions of the vascular system via distinct developmental pleiotropic molecular mechanisms.
Pathway-based, reaction-specific annotation of disease variants for elucidation of molecular phenotypes
Authors: Orlic-Milacic Marija , Rothfels Karen , Matthews Lisa , Wright Adam , Jassal Bijay , Shamovsky Veronica , Trinh Quang , Gillespie Marc E , Sevilla Cristoffer , Tiwari Krishna , Ragueneau Eliot , Gong Chuqiao , Stephan Ralf , May Bruce , Haw Robin , Weiser Joel , Beavers Deidre , Conley Patrick , Hermjakob Henning , Stein Lincoln D , D’Eustachio Peter , Wu Guanming
Published: May 2024

Germline and somatic mutations can give rise to proteins with altered activity, including both gain and loss-of-function. The effects of these variants can be captured in disease-specific reactions and pathways that highlight the resulting changes to normal biology. A disease reaction is defined as an aberrant reaction in which a variant protein participates. A disease pathway is defined as a pathway that contains a disease reaction. Annotation of disease variants as participants of disease reactions and disease pathways can provide a standardized overview of molecular phenotypes of pathogenic variants that is amenable to computational mining and mathematical modeling. Reactome (https://reactome.org/), an open source, manually curated, peer-reviewed database of human biological pathways, in addition to providing annotations for >11 000 unique human proteins in the context of ∼15 000 wild-type reactions within more than 2000 wild-type pathways, also provides annotations for >4000 disease variants of close to 400 genes as participants of ∼800 disease reactions in the context of ∼400 disease pathways. Functional annotation of disease variants proceeds from normal gene functions, described in wild-type reactions and pathways, through disease variants whose divergence from normal molecular behaviors has been experimentally verified, to extrapolation from molecular phenotypes of characterized variants to variants of unknown significance using criteria of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Reactome’s data model enables mapping of disease variant datasets to specific disease reactions within disease pathways, providing a platform to infer pathway output impacts of numerous human disease variants and model organism orthologs, complementing computational predictions of variant pathogenicity.

Database URL: https://reactome.org/
Accelerometer-based sedentary time and physical activity from childhood through young adulthood with progressive cardiac changes: a 13-year longitudinal study
Authors: Agbaje Andrew O
Published: May 2024

Aims

Longitudinal evidence on the relationship of sedentary time (ST), light-intensity physical activity (LPA), and moderate-to-vigorous-intensity physical activity (MVPA) with changes in cardiac structure and function in the paediatric population is scarce. This evidence is clinically important due to the impact ST can have on the long-term prognosis of healthy young population in the lifetime continuum. This prospective observational study examined the relationships of cumulative ST, LPA, and MVPA from childhood with longitudinal changes in cardiac structure and function.

Methods and results

This is a secondary analysis from the Avon Longitudinal Study of Parents and Children, UK birth cohort of 1682 children aged 11 years. Participants who had at least one follow-up timepoints accelerometer-measured ST, LPA, and MVPA over a period of 13 years and repeated echocardiography-measured cardiac structure and function at ages 17- and 24-year clinic visit were included. Left ventricular mass indexed for height2.7 (LVMI2.7) and left ventricular (LV) diastolic function from mitral E/A ratio (LVDF) were computed. Among 1682 children (mean [SD] age, 11.75 [0.24] years; 1054 [62.7%] females), the cumulative one-min/day increase in ST from ages 11 to 24 years was associated with progressively increased LVMI2.7 {effect estimate 0.002 g/m2.7 [confidence interval (CI) 0.001–0.003], P < 0.001}, irrespective of sex, obesity, and hypertensive status. Cumulative one-min/day increase in LPA was associated with a decreased LVMI2.7 (−0.005 g/m2.7 [−0.006 to −0.003], P < 0.0001) but an increased LVDF. Cumulative one-minute/day increase in MVPA was associated with progressively increased LVMI2.7 (0.003 g/m2.7 [0.001–0.006], P = 0.015).

Conclusion

ST contributed +40% to the 7-year increase in cardiac mass, MVPA increased cardiac mass by +5%, but LPA reduced cardiac mass by −49%. Increased ST may have long-term pathologic effects on cardiac structure and function during growth from childhood through young adulthood; however, engaging in LPA may enhance cardiac health in the young population.
Exercise effects on maternal vascular health and blood pressure during pregnancy and postpartum: a systematic review and meta-analysis
Authors: Pongpanit Karan , Dayan Natalie , Janaudis-Ferreira Tania , Roig Marc , Spahija Jadranka , Bertagnolli Mariane
Published: May 2024

Aims

This systematic review aimed to assess the effects of exercise training during pregnancy and the postpartum period on maternal vascular health and blood pressure (BP).

Methods and results

The outcome of interest was pulse wave velocity (PWV), flow-mediated dilation (FMD), and BP from pregnancy to 1-year postpartum. Five databases, including Ovid MEDLINE, EMBASE, CINAHL, Web of Science, and Cochrane Library, were systematically searched from inception to August 2023. Studies of randomized controlled trials (RCTs) comparing the effects of prenatal or postpartum exercise to a non-exercise control group were included. The risk of bias and the certainty of evidence were assessed. Random-effects meta-analyses and sensitivity analyses were conducted. In total, 20 RCTs involving 1221 women were included. Exercise training, initiated from Week 8 during gestation or between 6 and 14 weeks after delivery, with the programme lasting for a minimum of 4 weeks up to 6 months, showed no significant impact on PWV and FMD. However, it resulted in a significant reduction in systolic BP (SBP) [mean difference (MD): −4.37 mmHg; 95% confidence interval (CI): −7.48 to −1.26; P = 0.006] and diastolic BP (DBP) (MD: −2.94 mmHg; 95% CI: −5.17 to −0.71; P = 0.01) with very low certainty. Subgroup analyses revealed consistent trends across different gestational stages, types of exercise, weekly exercise times, and training periods.

Conclusion

Exercise training during pregnancy and the postpartum period demonstrates a favourable effect on reducing maternal BP. However, further investigations with rigorous methodologies and larger sample sizes are needed to strengthen these conclusions.
Translational control of MPS1 links protein synthesis with the initiation of cell division and spindle pole body duplication in Saccharomyces cerevisiae
Authors: Blank Heidi M , Alonso Annabel , Fabritius Amy S , Valk Ervin , Loog Mart , Winey Mark , Polymenis Michael
Published: May 2024

Protein synthesis underpins cell growth and controls when cells commit to a new round of cell division at a point in late G1 of the cell cycle called Start. Passage through Start also coincides with the duplication of the microtubule-organizing centers, the yeast spindle pole bodies, which will form the 2 poles of the mitotic spindle that segregates the chromosomes in mitosis. The conserved Mps1p kinase governs the duplication of the spindle pole body (SPB) in Saccharomyces cerevisiae. Here, we show that the MPS1 transcript has a short upstream open reading frame (uORF) that represses the synthesis of Mps1p. Mutating the MPS1 uORF makes the cells smaller, accelerates the appearance of Mps1p in late G1, and promotes completion of Start. Monitoring the SPB in the cell cycle using structured illumination microscopy revealed that mutating the MPS1 uORF enabled cells to duplicate their SPB earlier at a smaller cell size. The accelerated Start of MPS1 uORF mutants depends on the G1 cyclin Cln3p and the transcriptional repressor Whi5p but not on the Cln1,2p G1 cyclins. These results identify growth inputs in mechanisms that control duplication of the microtubule-organizing center and implicate these processes in the coupling of cell growth with division.
Biography of Vitis genomics: recent advances and prospective
Authors: Wang Yi , Ding Kangyi , Li Huayang , Kuang Yangfu , Liang Zhenchang
Published: May 2024

The grape genome is the basis for grape studies and breeding, and is also important for grape industries. In the last two decades, more than 44 grape genomes have been sequenced. Based on these genomes, researchers have made substantial progress in understanding the mechanism of biotic and abiotic resistance, berry quality formation, and breeding strategies. In addition, this work has provided essential data for future pangenome analyses. Apart from de novo assembled genomes, more than six whole-genome sequencing projects have provided datasets comprising almost 5000 accessions. Based on these datasets, researchers have explored the domestication and origins of the grape and clarified the gene flow that occurred during its dispersed history. Moreover, genome-wide association studies and other methods have been used to identify more than 900 genes related to resistance, quality, and developmental phases of grape. These findings have benefited grape studies and provide some basis for smart genomic selection breeding. Moreover, the grape genome has played a great role in grape studies and the grape industry, and the importance of genomics will increase sharply in the future.
Arthur Packets for Quasisplit GSp(2n) and GO(2n) Over a p-Adic Field
Authors: Xu Bin
Published: May 2024

We construct the Arthur packets for symplectic and even orthogonal similitude groups over a $p$-adic field and show that they are stable and satisfy the twisted endoscopic character relations.
Is the African Vaccine Manufacturing Accelerator a decoupling mechanism?
Authors: Awosusi Abiodun E
Published: May 2024

This article explores how the African Vaccine Manufacturing Accelerator can support the sustainable production of vaccines in Africa. It highlights the value of the accelerator in relation to the Regional Vaccine Manufacturing Collaborative. The author proposes that this novel financing instrument should be well-designed and implemented in line with the targets of the Partnerships for African Vaccine Manufacturing. It should not be a decoupling tool to appease the institutional environment of the global vaccine market, but a sustainable demonstration of the goodwill and commitment of political and technical leaders to ensure equitable access to routine and epidemic-related vaccines in Africa.
Assessment of Preanalytical Cerebrospinal Fluid Handling and Storage Factors on Measurement of Aβ1-42, Aβ1-40, and pTau181 Using an Automated Chemiluminescent Platform
Authors: Ho Sara , Darrow Jacqueline , De Simone Francesca , Calabro Amanda , Gannon Sara , Esquivel Rianne , Thakker Parmi , Khingelova Kristina , Rao Aruna , Zhang Yifan , Moghekar Abhay
Published: May 2024

Background

Standardizing cerebrospinal fluid (CSF) laboratory protocols will improve the reliability and availability of clinical biomarker testing required for prescription of novel Alzheimer disease (AD) therapies. This study evaluated several preanalytical handling and storage factors common to β-amyloid1-42 (Aβ1-42), β-amyloid1-40 (Aβ1-40), and phosphorylated tau (pTau181) concentrations including storage at different temperatures, extended cap contact, various mixing methods, and multiple freeze-thaw cycles.

Methods

Aβ1-42, Aβ1-40, and pTau181 concentrations were measured using LUMIPULSE G1200 automated assays. Samples were collected in polypropylene tubes of various volumes. Sample cap-contact was evaluated by storing samples in upright and inverted positions at either 4°C for 1 week or −80°C for 1 month. To assess mixing methods, samples were freeze-thawed and mixed by inversion, vortex, horizontal roller, or unmixed prior to assay sampling. The impact of successive freeze-thaw cycles was assessed through freezing, thawing, and analyzing CSF samples.

Results

Short-term storage at 4°C did not affect Aβ1-42, Aβ1-40, or pTau181 measurements in any tube type. Tube cap contact affected Aβ1-42 in 2.5 mL tubes and pTau181 levels in 10 mL tubes. No difference was observed between mixing methods. After 4 freeze-thaw cycles, Aβ1-42 significantly decreased but Aβ1-40 remained unchanged. Utilizing the Aβ1-42/Aβ1-40 ratio, Aβ1-42 values normalized, maintaining ratio values within ±5% of baseline measurements.

Conclusions

Storage of CSF at 4°C for 1 week or −80°C for 1 month did not significantly affect Aβ1-42, Aβ1-40, pTau181, or associated ratio measurements. Tube cap-contact impacted pTau181 and pTau181/Aβ1-42 values in larger tubes. Mixing methods are equivalent. The Aβ1-42/Aβ1-40 ratio compensates for freeze-thaw variability up to 4 cycles.
Evaluating site-of-care-related racial disparities in kidney graft failure using a novel federated learning framework
Authors: Tong Jiayi , Shen Yishan , Xu Alice , He Xing , Luo Chongliang , Edmondson Mackenzie , Zhang Dazheng , Lu Yiwen , Yan Chao , Li Ruowang , Siegel Lianne , Sun Lichao , Shenkman Elizabeth A , Morton Sally C , Malin Bradley A , Bian Jiang , Asch David A , Chen Yong
Published: May 2024

Objectives

Racial disparities in kidney transplant access and posttransplant outcomes exist between non-Hispanic Black (NHB) and non-Hispanic White (NHW) patients in the United States, with the site of care being a key contributor. Using multi-site data to examine the effect of site of care on racial disparities, the key challenge is the dilemma in sharing patient-level data due to regulations for protecting patients’ privacy.

Materials and Methods

We developed a federated learning framework, named dGEM-disparity (decentralized algorithm for Generalized linear mixed Effect Model for disparity quantification). Consisting of 2 modules, dGEM-disparity first provides accurately estimated common effects and calibrated hospital-specific effects by requiring only aggregated data from each center and then adopts a counterfactual modeling approach to assess whether the graft failure rates differ if NHB patients had been admitted at transplant centers in the same distribution as NHW patients were admitted.

Results

Utilizing United States Renal Data System data from 39 043 adult patients across 73 transplant centers over 10 years, we found that if NHB patients had followed the distribution of NHW patients in admissions, there would be 38 fewer deaths or graft failures per 10 000 NHB patients (95% CI, 35-40) within 1 year of receiving a kidney transplant on average.

Discussion

The proposed framework facilitates efficient collaborations in clinical research networks. Additionally, the framework, by using counterfactual modeling to calculate the event rate, allows us to investigate contributions to racial disparities that may occur at the level of site of care.

Conclusions

Our framework is broadly applicable to other decentralized datasets and disparities research related to differential access to care. Ultimately, our proposed framework will advance equity in human health by identifying and addressing hospital-level racial disparities.
A role for miRNAs in the regulation of brown adipose tissue whitening in goats (Capra Hircus)
Authors: Zhao Le , Li Minhao , Xiao Min , Chen Meixi , Yang Haili , Zhao Yongju
Published: May 2024

A study of the mechanism of and metabolic regulation of brown adipose tissue (BAT) production is important for improving the survival rate of young animals. In the present study, we observed that perirenal adipose tissue in goats undergoes a rapid BAT whitening after birth. However, the underlying regulatory mechanism remains unknown. To address this further, we investigated the role of miRNAs in regulating the whitening process of BAT in goats. First, we identified the dynamic expression profiles of miRNAs during the whitening of BAT in Dazu black goat using RNA-seq. We identified a total of 1374 miRNAs, including 408 existing miRNAs, 693 known miRNAs, and 273 novel miRNAs. By analysis of the differentially expressed miRNAs (DE miRNAs), we found that 102 highly expressed miRNAs, including chi-miR-144-3p, chi-miR-144-5p, chi-miR-378-5p, chi-miR-136-3p, chi-miR-381, chi-miR-323b, chi-miR-1197-3p, chi-miR-411b-3p, and chi-miR-487a-3p, were enriched in BAT. In addition, 60 highly expressed miRNAs, including chi-miR-184, chi-miR-193a, chi-miR-193b-3p, chi-let-7c-5p, and chi-let-7e-5p, were enriched in white fat-like tissue. An analysis of miRNAs that were linearly downregulated (profile 0) or linearly upregulated (profile 19) over the D0—D28 period found that these DE miRNAs were mainly enriched in the Hippo signaling pathway, Cytokine-cytokine receptor interactions, and the TGF-beta signaling pathway. Furthermore, we confirmed that chi-let-7e-5p promotes the proliferation and differentiation of brown adipocytes. These results should facilitate a better understanding of the molecular regulation of miRNAs involved in BAT whitening in goats.