bluuebunny/crossref_metadata_2025_split huggingface dataset:
Driving mosaicism: somatic variants in reference population databases and effect on variant interpretation in rare genetic disease
Authors: Avramović Vladimir , Frederiksen Simona Denise , Brkić Marjana , Tarailo-Graovac Maja 
Published: December 2021

AbstractBackgroundGenetic variation databases provide invaluable information on the presence and frequency of genetic variants in the ‘untargeted’ human population, aggregated with the primary goal to facilitate the interpretation of clinically important variants. The presence of somatic variants in such databases can affect variant assessment in undiagnosed rare disease (RD) patients. Previously, the impact of somatic mosaicism was only considered in relation to two Mendelian disease-associated genes. Here, we expand the analyses to identify additional mosaicism-prone genes in blood-derived reference population databases.ResultsTo identify additional mosaicism-prone genes relevant to RDs, we focused on known/previously established ClinVar pathogenic and likely pathogenic single-nucleotide variants, residing in genes associated with early onset, severe autosomal dominant diseases. We asked whether any of these variants are present in a higher-than-expected frequency in the reference population databases and whether there is evidence of somatic origin (i.e., allelic imbalance) rather than germline heterozygosity (~ half of the reads supporting alternative allele). The mosaicism-prone genes identified were further categorized according to the processes they are involved in. Beyond the previously reportedASXL1andDNMT3A, we identified 7 additional autosomal dominant RD-associated genes with known pathogenic single-nucleotide variants present in the reference population databases and good evidence of allelic imbalance:BRAF,CBL,FGFR3, IDH2,KRAS, PTPN11andSETBP1. From this group of 9 genes, the majority (n = 7) was important for hematopoiesis. In addition, 4 of these genes were involved in cell proliferation. Further assessment of the known 156 hematopoietic genes led to identification of 48 genes (21 not yet associated with RDs) with at least some evidence of mosaicism detectable in reference population databases.ConclusionsThese results stress the importance of considering genes involved in hematopoiesis and cell proliferation when interpreting the presence and frequency of genetic variants in blood-derived reference population databases, both public and private. This is especially important when considering new variants of uncertain significance in known hematopoietic/cell proliferation RD genes and future novel gene–disease associations involving this class of genes.
Determination of the source parameters of the 2011 Tohoku-Oki earthquake from three-component pre-P gravity signals recorded by dense arrays in Japan
Authors: Kimura Masaya , Kame Nobuki , Watada Shingo , Araya Akito , Kunugi Takashi , Wang Rongjiang 
Published: December 2021

AbstractDynamic earthquake rupture causes mass redistribution around the fault, and the emitted propagating seismic waves are accompanied by bulk density perturbations. Both processes cause transient gravity changes prior to the arrival of P-waves. Such pre-P gravity signals have been detected in previous studies of several large earthquakes. However, the detections were limited to the vertical component of the signal owing to the high noise level in the horizontal records. In this study, we analyzed dense tiltmeter array data in Japan to search for the horizontal components of the signal from the 2011 Mw 9.1 Tohoku-Oki earthquake. Based on the synthetic waveforms computed for a realistic Earth model, we stacked the horizontal records and identified a signal that evidently exceeded the noise level. We further performed a waveform inversion analysis to estimate the source parameters. The horizontal tiltmeter data, combined with the vertical component of the broadband seismometer array data, yielded a constraint on the dip angle and magnitude of the earthquake in the ranges of 11.5°–15.3° and 8.75°–8.92°, respectively. Our results indicate that the analysis of the three components of the pre-P gravity signal avoids the intrinsic trade-off problem between the dip angle and seismic moment in determining the source mechanism of shallow earthquakes. Pre-P gravity signals open a new observation window for earthquake source studies.
Graphical Abstract
Socio-economic and health costs of porcine/human cysticercosis, neurocysticercosis and epilepsy to small-scale pig producers in Tanzania
Authors: Kayuni Emmanuel Nestory 
Published: December 2021

Abstract
Background
Porcine cysticercosis, human cysticercosis, neurocysticercosis, and epilepsy pose a serious public health risk and lead to economic losses to the small-scale pig farmers in Tanzania’s rural areas. It also resulted in lowering the pig’s prices, high treatment expenses, lower labour productivity, and social discrimination. In Tanzania, small-scale pig producers are unaware of the methods that are used to manage and prevent the diseases associated with Taenia solium.

Main body
The main goal of the reviewed article was to investigate the socio-economic and health costs of porcine/human cysticercosis, neurocysticercosis, and epilepsy on small-scale pig producers in Tanzania. Several search engines yielded 80 peer-reviewed publications, 44 of which were considered to be relevant to the study. Taenia solium cysticercosis has been reported to cause huge financial losses in the management of pigs posing a burden in terms of vaccination and treatment.

Conclusion
The information on porcine/human cysticercosis, neurocysticercosis, and epilepsy is still insufficient in Tanzania. Poor habits, negative perceptions, and attitudes are the result of this misinformation. This review suggests that health education should be emphasized as one of the intervention methods for eliminating all forms of cysticercosis and epilepsy in Tanzania to promote and increase awareness about all forms of cysticercosis and epilepsy in rural areas.
RIPASA versus Alvarado score in the assessment of suspected appendicitis in children: a prospective study
Authors: Öztaş Tülin , Asena Muhammet 
Published: December 2021

Abstract
Background
Diagnosis of acute appendicitis remains a problem in children with right lower quadrant pain.
Challenging diagnosis and fears of missing an inflamed appendix may lead to a negative appendectomy. Many scoring systems have been developed to reduce ambiguities in the diagnosis of appendicitis. Alvarado is one of the most commonly used scoring methods in pediatric patients. The RIPASA score is considered to be a better diagnostic scoring method in adults compared to Alvarado. The present study aims to compare RIPASA and Alvarado scoring systems in determining the possibility of acute appendicitis in children with right lower quadrant pain.
This study included 179 consecutive pediatric patients who were referred to pediatric surgery with suspicion of acute appendicitis. The cut-off value was >7.5 for the RIPASA score vs. ≥7 for the Alvarado score. The possibility of appendicitis was divided into three groups for the Alvarado score and four groups for the RIPASA score.

Results
In this study, 158 of 179 patients were operated on. In 140 of the operated patients, the diagnosis of appendicitis was confirmed by histopathology. The negative appendectomy rate was 11.4%. Specificity and negative predictive value of RIPASA score were higher than those of Alvarado (p<0.001). No difference was found between the two scores concerning sensitivity, positive predictive value, and the area under the receiver operator characteristics curve (p>0.05).

Conclusion
The RIPASA scoring system can be used as an alternative to the Alvarado scoring system in the management of patients with right lower quadrant pain in emergency services and pediatric outpatient clinics. With the use of the RIPASA score, more patients with a low likelihood of appendicitis can be detected and further contributed to the reduction of the negative appendectomy rate.
Outcomes of Patients Placed in an Emergency Department Observation Unit of a Comprehensive Cancer Center
Authors: Chaftari Patrick , Lipe Demis N. , Wattana Monica K. , Qdaisat Aiham , Krishnamani Pavitra P. , Thomas Jomol , Elsayem Ahmed F. , Sandoval Marcelo 
Published: December 2021

PURPOSE: Emergency department observation units (EDOUs) have been shown to decrease length of stay and improve cost effectiveness. Yet, compared with noncancer patients, patients with cancer are placed in EDOUs less often. In this study, we aimed to describe patients who were placed in a cancer center's EDOU to discern their clinical characteristics and outcomes. METHODS: We performed a retrospective observational study that included all patients age 18 years and older who presented to our emergency department (ED) and were placed in the EDOU between March 1, 2019, and February 29, 2020. The patients' electronic medical records were queried for demographics, comorbidities, diagnosis at the time of placement in the EDOU, length of stay, disposition from the EDOU, ED return within 72 hours after discharge from the EDOU, and mortality outcomes at 14 and 30 days. RESULTS: A total of 2,461 visits were eligible for analysis. Cancer-related pain was the main reason for observation in more than one quarter of the visits. The median length of stay in the EDOU was approximately 23 hours, and 69.6% of the patients were discharged. The ED return rate for unscheduled visits at 72 hours was 1.9%. The 14- and 30-day mortality rates were significantly higher for patients who were admitted than for those who were discharged (14 days: 1.7% v 0.3%, P < .001; 30 days: 5.9% v 1.8%, P < .001). CONCLUSION: Our data suggest that placing patients with cancer in EDOUs is safe, reduces admissions, and reserves hospital resources for patients who can receive the most benefit without compromising care.
DamID transcriptional profiling identifies the Snail/Scratch transcription factor Kahuli as an Alk target in the Drosophila visceral mesoderm
Authors: Mendoza-Garcia Patricia , Basu Swaraj , Sukumar Sanjay Kumar , Arefin Badrul , Wolfstetter Georg , Anthonydhason Vimala , Molander Linnea , Uçkun Ezgi , Lindehell Henrik , Lebrero-Fernandez Cristina , Larsson Jan , Larsson Erik , Bemark Mats , Palmer Ruth H. 
Published: December 2021

ABSTRACT
Development of the Drosophila visceral muscle depends on Anaplastic Lymphoma Kinase (Alk) receptor tyrosine kinase (RTK) signaling, which specifies founder cells (FCs) in the circular visceral mesoderm (VM). Although Alk activation by its ligand Jelly Belly (Jeb) is well characterized, few target molecules have been identified. Here, we used targeted DamID (TaDa) to identify Alk targets in embryos overexpressing Jeb versus embryos with abrogated Alk activity, revealing differentially expressed genes, including the Snail/Scratch family transcription factor Kahuli (Kah). We confirmed Kah mRNA and protein expression in the VM, and identified midgut constriction defects in Kah mutants similar to those of pointed (pnt). ChIP and RNA-Seq data analysis defined a Kah target-binding site similar to that of Snail, and identified a set of common target genes putatively regulated by Kah and Pnt during midgut constriction. Taken together, we report a rich dataset of Alk-responsive loci in the embryonic VM and functionally characterize the role of Kah in the regulation of embryonic midgut morphogenesis.
Maternal Smc3 protects the integrity of the zygotic genome through DNA replication and mitosis
Authors: Yueh Wei-Ting , Singh Vijay Pratap , Gerton Jennifer L. 
Published: December 2021

ABSTRACT
Aneuploidy is frequently observed in oocytes and early embryos, begging the question of how genome integrity is monitored and preserved during this crucial period. SMC3 is a subunit of the cohesin complex that supports genome integrity, but its role in maintaining the genome during this window of mammalian development is unknown. We discovered that, although depletion of Smc3 following meiotic S phase in mouse oocytes allowed accurate meiotic chromosome segregation, adult females were infertile. We provide evidence that DNA lesions accumulated following S phase in SMC3-deficient zygotes, followed by mitosis with lagging chromosomes, elongated spindles, micronuclei, and arrest at the two-cell stage. Remarkably, although centromeric cohesion was defective, the dosage of SMC3 was sufficient to enable embryogenesis in juvenile mutant females. Our findings suggest that, despite previous reports of aneuploidy in early embryos, chromosome missegregation in zygotes halts embryogenesis at the two-cell stage. Smc3 is a maternal gene with essential functions in the repair of spontaneous damage associated with DNA replication and subsequent chromosome segregation in zygotes, making cohesin a key protector of the zygotic genome.
Flight activity and age cause wing damage in house flies
Authors: Wehmann Henja-Niniane , Engels Thomas , Lehmann Fritz-Olaf 
Published: December 2021

ABSTRACTWing damage attenuates aerial performance in many flying animals such as birds, bats and insects. Insect wings are especially light in order to reduce inertial power requirements for flight at elevated wing flapping frequencies. There is a continuing debate on the factors causing wing damage in insects, including collisions with objects, mechanical stress during flight activity, and aging. This experimental study addressed the reasons for and significance of wing damage for flight in the house fly Musca domestica. We determined natural wing area loss under two housing conditions and recorded flight activity and flight ability throughout the animals' lifetime. Our data show that in animals with eventually pronounced damage, wing damage occurs on average after 6 h of flight, is sex specific and depends on housing conditions. Statistical tests show that physiological age and flight activity have similar significance as predictors for wing damage. Tests on freely flying flies showed that minimum wing area for active flight is approximately 10–34% below the initial area and requires a left–right wing area asymmetry of less than approximately 25%. Our findings broadly confirm predictions from simple aerodynamic theory based on mean wing velocity and area, and are also consistent with previous wing damage measurements in other insect species.
Tissue- and substrate-dependent mitochondrial responses to acute hypoxia–reoxygenation stress in a marine bivalve (Crassostrea gigas
)
Authors: Adzigbli Linda , Sokolov Eugene P. , Ponsuksili Siriluck , Sokolova Inna M. 
Published: December 2021

ABSTRACT
Hypoxia is a major stressor for aquatic organisms, yet intertidal organisms such as the oyster Crassostrea gigas are adapted to frequent oxygen fluctuations by metabolically adjusting to shifts in oxygen and substrate availability during hypoxia–reoxygenation (H/R). We investigated the effects of acute H/R stress (15 min at ∼0% O2 and 10 min reoxygenation) on isolated mitochondria from the gill and the digestive gland of C. gigas respiring on different substrates (pyruvate, glutamate, succinate, palmitate and their mixtures). Gill mitochondria showed better capacity for amino acid and fatty acid oxidation compared with mitochondria from the digestive gland. Mitochondrial responses to H/R stress strongly depended on the substrate and the activity state of mitochondria. In mitochondria oxidizing NADH-linked substrates, exposure to H/R stress suppressed oxygen consumption and generation of reactive oxygen species (ROS) in the resting state, whereas in the ADP-stimulated state, ROS production increased despite little change in respiration. As a result, electron leak (measured as H2O2 to O2 ratio) increased after H/R stress in the ADP-stimulated mitochondria with NADH-linked substrates. In contrast, H/R exposure stimulated succinate-driven respiration without an increase in electron leak. Reverse electron transport (RET) did not significantly contribute to succinate-driven ROS production in oyster mitochondria except for a slight increase in the OXPHOS state during post-hypoxic recovery. A decrease in NADH-driven respiration and ROS production, enhanced capacity for succinate oxidation and resistance to RET might assist in post-hypoxic recovery of oysters mitigating oxidative stress and supporting rapid ATP re-synthesis during oxygen fluctuations, as is commonly observed in estuaries and intertidal zones.
Assessing equity and the determinants of socio-economic impacts of COVID-19: Results from a cross-sectional survey in three counties in Kenya
Authors: Oyando Robinson , Orangi Stacey , Mwanga Daniel , Pinchoff Jessie , Abuya Timothy , Muluve Eva , Mbushi Faith , Austrian Karen , Barasa Edwine 
Published: December 2021

Background: COVID-19 mitigation measures have major ramifications on all aspects of people’s livelihoods. Based on data collected in February 2021, we present an analysis of the socio-economic impacts of COVID-19 mitigation measures in three counties in Kenya. Methods: We conducted a cross-sectional phone-based survey in three counties in Kenya to assess the level of disruption across seven domains: income, food insecurity, schooling, domestic tension/violence, communal violence, mental health, and decision-making. An overall disruption index was computed from the seven domains using principal component analysis. We used a linear regression model to examine the determinants of vulnerability to disruptions as measured by the index. We used concentration curves and indices to assess inequality in the disruption domains and the overall disruption index. Results: The level of disruption in income was the highest (74%), while the level of disruption for domestic tension/violence was the lowest (30%). Factors associated with increased vulnerability to the overall disruption index included: older age, being married, belonging in the lowest socio-economic tertile and receiving COVID-19 related assistance. The concentration curves showed that all the seven domains of disruption were disproportionately concentrated among households in the lowest socio-economic tertile, a finding that was supported by the concentration index of the overall disruption index (CI = - 0.022; p = 0.074). Conclusion: The COVID-19 mitigation measures resulted in unintended socio-economic effects that unfairly affected certain vulnerable groups such as those in the lowest socio-economic group and the elderly. Measures to protect households against the adverse socio-economic effects of the pandemic should be scaled up and targeted to the most vulnerable, with attention to the constantly evolving nature of the pandemic.
Characterising the transcriptome of hypersegmented human neutrophils
Authors: Fox Eleonore , Jones Rowena , Samanta Romit , Summers Charlotte 
Published: December 2021

Background: Mature human neutrophils are characterised by their multilobed nuclear morphology. Neutrophil hypersegmentation, a pathologic nuclear phenotype, has been described in the alveolar compartment of patients with acute respiratory distress syndrome and in several other contexts. This study aimed to characterise the transcriptional changes associated with neutrophil hypersegmentation. Methods: A model of hypersegmentation was established by exposing healthy peripheral blood neutrophils to the angiotensin converting enzyme inhibitor (ACEi) captopril. Laser capture microdissection (LCM) was then adapted to isolate a population of hypersegmented neutrophils. Transcriptomic analysis of microdissected hypersegmented neutrophils was undertaken using ribonucleic acid (RNA) sequencing. Differential gene expression (DEG) and enrichment pathway analysis were conducted to investigate the mechanisms underlying hypersegmentation. Results: RNA-Seq analysis revealed the transcriptomic signature of hypersegmented neutrophils, with five genes differentially expressed. VCAN, PADI4 and DUSP4 were downregulated, while LTF and PSMC4 were upregulated. Modulated pathways included histone modification, protein-DNA complex assembly and antimicrobial humoral response. The role of PADI4 was further validated using the small molecule inhibitor, Cl-amidine. Conclusions: Hypersegmented neutrophils display a marked transcriptomic signature, characterised by the differential expression of five genes. This study provides insights into the mechanisms underlying neutrophil hypersegmentation and describes a novel method to isolate and sequence neutrophils based on their morphologic subtype.
Naive Learning Through Probability Overmatching
Authors: Arieli Itai , Babichenko Yakov , Mueller-Frank Manuel 
Published: December 2021

Naïve Learning in a Binary Action, Social Network Environment In “Naïve Learning Through Probability Overmatching,” I. Arieli, Y. Babichenko, and M. Mueller-Frank consider an environment where privately informed agents select a binary action repeatedly observing the past actions of their neighbors in a social network. Rational inference has been shown to be exceedingly complex in this environment. Instead, this paper focuses on boundedly rational agents that form beliefs according to discretized DeGroot updating and apply a decision rule that assigns a (mixed) action to each belief. It is shown that naïve learning, where the long run actions of all agents are optimal given their pooled private information, can be achieved in any strongly connected network if beliefs satisfy a high level of inertia and the decision rule coincides with probability overmatching. The main difference to existing naïve learning results is that here it is shown to hold (1) for binary rather than uncountable action spaces and (2) even for network and information structures where Bayesian agents fail to learn.