bluuebunny/crossref_metadata_2025 huggingface dataset:
An allele-sharing, moment-based estimator of global, population-specific and population-pair FST under a general model of population structure
Authors: Goudet Jerome , Weir Bruce S.
Published: November 2023

Being able to properly quantify genetic differentiation is key to understanding the evolutionary potential of a species. One central parameter in this context is FST, the mean coancestry within populations relative to the mean coancestry between populations. Researchers have been estimating FST globally or between pairs of populations for a long time. More recently, it has been proposed to estimate population-specific FST values, and population-pair mean relative coancestry. Here, we review the several definitions and estimation methods of FST, and stress that they provide values relative to a reference population. We show the good statistical properties of an allele-sharing, method of moments based estimator of FST (global, population-specific and population-pair) under a very general model of population structure. We point to the limitation of existing likelihood and Bayesian estimators when the populations are not independent. Last, we show that recent attempts to estimate absolute, rather than relative, mean coancestry fail to do so.
Phosphate starvation decouples cell differentiation from DNA replication control in the dimorphic bacterium Caulobacter crescentus
Authors: Hallgren Joel , Koonce Kira , Felletti Michele , Mortier Julien , Turco Eloisa , Jonas Kristina
Published: November 2023

Upon nutrient depletion, bacteria stop proliferating and undergo physiological and morphological changes to ensure their survival. Yet, how these processes are coordinated in response to distinct starvation conditions is poorly understood. Here we compare the cellular responses of Caulobacter crescentus to carbon (C), nitrogen (N) and phosphorus (P) starvation conditions. We find that DNA replication initiation and abundance of the replication initiator DnaA are, under all three starvation conditions, regulated by a common mechanism involving the inhibition of DnaA translation. By contrast, cell differentiation from a motile swarmer cell to a sessile stalked cell is regulated differently under the three starvation conditions. During C and N starvation, production of the signaling molecules (p)ppGpp is required to arrest cell development in the motile swarmer stage. By contrast, our data suggest that low (p)ppGpp levels under P starvation allow P-starved swarmer cells to differentiate into sessile stalked cells. Further, we show that limited DnaA availability, and consequently absence of DNA replication initiation, is the main reason that prevents P-starved stalked cells from completing the cell cycle. Together, our findings demonstrate that C. crescentus decouples cell differentiation from DNA replication initiation under certain starvation conditions, two otherwise intimately coupled processes. We hypothesize that arresting the developmental program either as motile swarmer cells or as sessile stalked cells improves the chances of survival of C. crescentus during the different starvation conditions.
Accurate phenotypic classification and exome sequencing allow identification of novel genes and variants associated with adult-onset hearing loss
Authors: Lewis Morag A. , Schulte Jennifer , Matthews Lois , Vaden Kenneth I. , Steves Claire J. , Williams Frances M. K. , Schulte Bradley A. , Dubno Judy R. , Steel Karen P.
Published: November 2023

Adult-onset progressive hearing loss is a common, complex disease with a strong genetic component. Although to date over 150 genes have been identified as contributing to human hearing loss, many more remain to be discovered, as does most of the underlying genetic diversity. Many different variants have been found to underlie adult-onset hearing loss, but they tend to be rare variants with a high impact upon the gene product. It is likely that combinations of more common, lower impact variants also play a role in the prevalence of the disease. Here we present our exome study of hearing loss in a cohort of 532 older adult volunteers with extensive phenotypic data, including 99 older adults with normal hearing, an important control set. Firstly, we carried out an outlier analysis to identify genes with a high variant load in older adults with hearing loss compared to those with normal hearing. Secondly, we used audiometric threshold data to identify individual variants which appear to contribute to different threshold values. We followed up these analyses in a second cohort. Using these approaches, we identified genes and variants linked to better hearing as well as those linked to worse hearing. These analyses identified some known deafness genes, demonstrating proof of principle of our approach. However, most of the candidate genes are novel associations with hearing loss. While the results support the suggestion that genes responsible for severe deafness may also be involved in milder hearing loss, they also suggest that there are many more genes involved in hearing which remain to be identified. Our candidate gene lists may provide useful starting points for improved diagnosis and drug development.
Efficient sex separation by exploiting differential alternative splicing of a dominant marker in Aedes aegypti
Authors: Weng Shih-Che , Antoshechkin Igor , Marois Eric , Akbari Omar S.
Published: November 2023

Only female mosquitoes consume blood giving them the opportunity to transmit deadly human pathogens. Therefore, it is critical to remove females before conducting releases for genetic biocontrol interventions. Here we describe a robust sex-sorting approach termed SEPARATOR (Sexing Element Produced by Alternative RNA-splicing of A Transgenic Observable Reporter) that exploits sex-specific alternative splicing of an innocuous reporter to ensure exclusive dominant male-specific expression. Using SEPARATOR, we demonstrate reliable sex selection from early larval and pupal stages in Aedes aegypti, and use a Complex Object Parametric Analyzer and Sorter (COPAS) to demonstrate scalable high-throughput sex-selection of first instar larvae. Additionally, we use this approach to sequence the transcriptomes of early larval males and females and find several genes that are sex-specifically expressed. SEPARATOR can simplify mass production of males for release programs and is designed to be cross-species portable and should be instrumental for genetic biocontrol interventions.
Minimal effective dose of bedaquiline administered orally and activity of a long acting formulation of bedaquiline in the murine model of leprosy
Authors: Chauffour Aurélie , Lounis Nacer , Andries Koen , Jarlier Vincent , Veziris Nicolas , Aubry Alexandra
Published: November 2023

Background

Bedaquiline (BDQ), by targeting the electron transport chain and having a long half-life, is a good candidate to simplify leprosy treatment. Our objectives were to (i) determine the minimal effective dose (MED) of BDQ administered orally, (ii) evaluate the benefit of combining two inhibitors of the respiratory chain, BDQ administered orally and clofazimine (CFZ)) and (iii) evaluate the benefit of an intramuscular injectable long-acting formulation of BDQ (intramuscular BDQ, BDQ-LA IM), in a murine model of leprosy.

Methodology/Principal findings

To determine the MED of BDQ administered orally and the benefit of adding CFZ, 100 four-week-old female nude mice were inoculated in the footpads with 5x103 bacilli of M. leprae strain THAI53. Mice were randomly allocated into: 1 untreated group, 5 groups treated with BDQ administered orally (0.10 to 25 mg/kg), 3 groups treated with CFZ 20 mg/kg alone or combined with BDQ administered orally 0.10 or 0.33 mg/kg, and 1 group treated with rifampicin (RIF) 10 mg/kg. Mice were treated 5 days a week during 24 weeks.

To evaluate the benefit of the BDQ-LA IM, 340 four-week-old female swiss mice were inoculated in the footpads with 5x103 to 5x101 bacilli (or 5x100 for the untreated control group) of M. leprae strain THAI53. Mice were randomly allocated into the following 11 groups treated with a single dose (SD) or 3 doses (3D) 24h after the inoculation: 1 untreated group, 2 treated with RIF 10 mg/kg SD or 3D, 8 treated with BDQ administered orally or BDQ-LA IM 2 or 20 mg/kg, SD or 3D.

Twelve months later, mice were sacrificed and M. leprae bacilli enumerated in the footpad.

All the footpads became negative with BDQ at 3.3 mg/kg. The MED of BDQ administered orally against M. leprae in this model is therefore 3.3 mg/kg. The combination of CFZ and BDQ 10-fold lower than this MED did not significantly increase the bactericidal activity of CFZ. The BDQ-LA IM displayed similar or lower bactericidal activity than the BDQ administered orally.

Conclusion

We demonstrated that the MED of BDQ administered orally against M. leprae was 3.3 mg/kg in mice and BDQ did not add significantly to the efficacy of CFZ at the doses tested. BDQ-LA IM was similar or less active than BDQ administered orally at equivalent dosing and frequency but should be tested at higher dosing in order to reach equivalent exposure in further experiments.
The frequency of complications in a cohort of patients diagnosed with hemophilia A and hemophilia B receiving prophylactic treatment in Colombia: A retrospective noninterventional study
Authors: Machado Alba Jorge E. , Wilches-Gutierrez Juan David , Arias-Osorio Diana Rocio , Reyes Juan Manuel , Nakandakari Maria Lourdes , Ospina-Arzuaga Harrison David , Gaviria-Mendoza Andres , Castaño-Gamboa Natalia , Valladales-Restrepo Luis Fernando , Machado-Duque Manuel E.
Published: November 2023

Introduction

Hemophilia A and B are disorders associated with the deficit of coagulation factors VIII and IX.

Objective

Was to determine the incidence of complications in a cohort of patients diagnosed with moderate and severe hemophilia A or B under treatment in a specialized institution.

Methods

A retrospective study of a cohort of patients with replacement therapy for hemophilia A or B, evaluating treatment and complications between January/2012 and July/2019. Sociodemographic, clinical and disease management-related variables were extracted from the medical records. Time to inhibitor development and rate associated with bleeding and hospitalizations were evaluated.

Results

A total of 159 male patients were identified with hemophilia A (n = 140; 88.1%) and B (n = 19; 11.9%) with a mean follow-up of 5.9±2.3 years. The mean age was 23.6±16.1 years, hemophilia was reported as severe in 125 patients in hemophilia A (89.3%) and 13 patients in hemophilia B (68.4%). Primary prophylaxis was registered in 17.0% of patients, 44.7% secondary, and 38.3% tertiary, with recombinant factors (n = 84; 52.8%) followed by plasma derived factors (n = 75; 47.2%). The incidence of inhibitor development was 0.3 per 100 patients/year, with mean time to event of 509 days. The incidence of bleeding was 192 per 100 patients/year, especially at the joint (n = 99; 62.3%) and muscle (n = 25; 15.7%) level. The incidence of hospitalization was 3.7 per 100 patients/year.

Conclusions

The most common complication was joint bleeding which was expected in this type of patients. Low proportion of patients developed factor inhibitors during the follow up.
Associations between white matter integrity and postural control in adults with traumatic brain injury
Authors: Zampieri Cris , Leary Jacob B. , Shahim Pashtun , Damiano Diane , Ho Pei-Shu , Pham Dzung L. , Chan Leighton
Published: November 2023

Abnormalities of postural sway have been extensively reported in traumatic brain injury (TBI). However, the underlying neural correlates of balance disturbances in TBI remain to be elucidated. Studies in children with TBI have reported associations between the Sensory Organization Test (SOT) and measures of white matter (WM) integrity with diffusion tensor imaging (DTI) in brain areas responsible for multisensory integration. This study seeks to replicate those associations in adults as well as explore relationships between DTI and the Limits of Stability (LOS) Test. Fifty-six participants (43±17 years old) with a history of TBI were tested 30 days to 5 years post-TBI. This study confirmed results in children for associations between the SOT and the medial lemniscus as well as middle cerebellar peduncle, and revealed additional associations with the posterior thalamic radiation. Additionally, this study found significant correlations between abnormal LOS scores and impaired WM integrity in the cingulum, corpus callosum, corticopontine and corticospinal tracts, fronto-occipital fasciculi, longitudinal fasciculi, medial lemniscus, optic tracts and thalamic radiations. Our findings indicate the involvement of a broad range of WM tracts in the control of posture, and demonstrate the impact of TBI on balance via disruptions to WM integrity.
The effects of fatigue on linear and angular kinematics during bilateral squat
Authors: Erman Berkant , Vural Faik , Dopsaj Milivoj , Ozkol Mehmet Zeki , Kose Damla Ercan , Aksit Tolga
Published: November 2023

This study was aimed to analyze in detail how the fatigue effects to kinematic parameters of body weight squat exercise (BSQ) by dividing a squat cycle into four different regions. Twenty-one male athletes participated in this study. Participants were divided into two groups according to their lower limb muscle ratio (LLMR). The BSQ was performed until participants were unable to continue the exercise due to the fatigue. Linear and angular kinematics were obtained by motion analysis software which has high validity and reliability. There was no significant but had large effect size interaction between fatigue conditions and LLMR groups in terms of knee ROM in the extension phase and hip angular velocity in braking phase of the flexion (0.08 > p >0.05, 0.18 > ηρ2 > 0.16). Fatigue condition did not have a significant effect on the duration in the acceleration and braking phases of BSQ (p > 0.05). There were many significant main effects on kinematics in the different regions due to the fatigue (0.01 < p <0.05, 0.44 > ηρ2 > 0.14). In the fatigue condition, there was a polynomial relationship between velocity of shoulder and hip joints (R2flex = 0.82, R2ext = 0.72) rather than linear (R2flex = 0.64, R2ext = 0.53) and coefficient correlations also decreased (rflex = 0.88 to 0.80, rext = 0.92 to 0.73). The sticking region was observed in the non-fatigue condition and disappeared when fatigue occurred. These results suggest that LLMR may be taken into consideration in the squat exercises, joint tracking may vary for velocity-based squat training and pre-test for sticking region observation may be apply with the BSQ.
Meta-analysis of diagnostic accuracy of nucleic acid amplification tests for abdominal tuberculosis
Authors: Shen Yanqin , Fang Likui , Ye Bo , Yu Guocan
Published: November 2023

Background

Abdominal tuberculosis (TB) is a severe extrapulmonary TB, which can lead to serious complications. Early diagnosis and treatment are very important for the prognosis and the diagnosis of abdominal TB is still difficult.

Methods

We searched PubMed, the Cochrane Library, Embase, China National Knowledge Infrastructure, and the Wanfang database for studies evaluating the diagnostic accuracy of NAATs for abdominal TB until August 2020. Any types of study design with full text were sought and included. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. Subgroup analysis, meta-regression analysis and sensitivity analysis were used to explore the sources of heterogeneity. Stata version 15.0 with the midas command packages was used to carry out meta-analyses.

Results

We included a total of 78 independent studies from 53 articles; 64 with CRS as the reference standard, and 14 with culture as the reference standard. The pooled sensitivity, specificity, and the areas under summary receiver operating characteristic (SROC) curves (AUC) were 58% (51%–64%; I2 = 87%), 99% (97%–99%; I2 = 81%), and 0.92 (0.89–0.94) compared with CRS, respectively. The pooled sensitivity, specificity, and the AUC values of the SROC were 80% (66%–90%; I2 = 56%), 96% (92%–98%; I2 = 84%), and 0.97 (0.95–0.98) compared with culture, respectively. The heterogeneity of sensitivity and specificity was significant.

Conclusions

NAATs had excellent efficacy in the diagnosis of abdominal TB regardless of the reference standard and regardless of the subtype of abdominal TB. Multiplex PCR with multiple target genes may improve diagnostic sensitivity, and stool specimens may also be used for the diagnosis of abdominal TB in addition to tissue and ascites.
Attitudes and perceptions towards public health safety measures during a global health crisis: Social and personal consequences
Authors: Terzis Lauren D. , Saltzman Leia Y. , Lowman J. Heath , Logan Dana A. , Hansel Tonya C.
Published: November 2023

The COVID-19 pandemic that spread throughout the globe has significantly altered our social and personal relationships. During the early phase of the pandemic, pharmaceutical interventions such as vaccine research and production were still in development, with international health agencies and governments promoting public health safety measures such as limiting mobility, school and work closures, lockdowns, economic incentives, mask-wearing, social distancing, quarantine, and hygiene to reduce the spread and flatten the curve regarding transmission and hospitalization. During the early wave (May 2020 through July 2020), we utilized a qualitative longitudinal research design coupled with weekly Zoom diary entries to investigate participant (n = 14) experiences. In doing so, we captured participant attitudes towards public health safety measures, as well as perceptions of social and interpersonal relationships during the pandemic. The main themes that emerged in our findings include feelings of safety and preparedness, personal accountability and collective responsibility, and changes to social life and relationships. While individuals have learned how to live with the pandemic, and have a new sense of normalcy, lessons learned from the impact of public health measures and social relationships have applicability moving forward post-pandemic. In particular, how to best protect against the deleterious effects of isolation during a future public health crisis.
Adenylate cyclase toxin of Bordetella parapertussis disrupts the epithelial barrier granting the bacterial access to the intracellular space of epithelial cells
Authors: Gorgojo Juan Pablo , Carrica Mariela del Carmen , Baroli Carlos Manuel , Valdez Hugo Alberto , Alvarez Hayes Jimena , Rodriguez Maria Eugenia
Published: November 2023

B. parapertussis is one of the etiological agents of whooping cough. Once inhaled, the bacteria bind to the respiratory epithelium and start the infection. Little is known about this first step of host colonization and the role of the human airway epithelial barrier on B. parapertussis infection. We here investigated the outcome of the interaction of B. parapertussis with a polarized monolayer of respiratory epithelial cells. Our results show that B. parapertussis preferentially attaches to the intercellular boundaries, and causes the disruption of the tight junction integrity through the action of adenylate cyclase toxin (CyaA). We further found evidence indicating that this disruption enables the bacterial access to components of the basolateral membrane of epithelial cells to which B. parapertussis efficiently attaches and gains access to the intracellular location, where it can survive and eventually spread back into the extracellular environment. Altogether, these results suggest that the adenylate cyclase toxin enables B. parapertussis to overcome the epithelial barrier and eventually establish a niche of persistence within the respiratory epithelial cells.
A comparison of traumatic experiences and human rights violations of persons with mental health conditions or psychosocial disabilities and persons with other disabilities
Authors: Hashimoto Jin , Izutsu Takashi , Sunagozaka Shodai , Iiyama Satoshi , Tsutsumi Atsuro
Published: November 2023

This study compares the traumatic and human rights violation experiences of persons with mental health conditions or psychosocial disabilities and those of persons with other disabilities in the Philippines. Additionally, the role of gender in exposure to traumatic experience and human rights protection levels is explored. Of those registered as persons with disabilities in the city of Muntinlupa, 3000 subjects were randomly selected and 1,024 among them (Male = 510, Female = 512, Others = 2) agreed to participate in this study. This comparative study adopts a cross-sectional design. The survey was conducted using a structured questionnaire. The researchers mobilized health workers, officially recruited by the city, to visit the target participants’ houses and to distribute the questionnaires to collect data. The questionnaire comprises items related to the participants’ socio-demographic characteristics, exposure to traumatic experiences, and human rights-based well-being. Regarding the frequency of exposure to traumatic experiences, a little difference was found in physical domestic violence (abuse) between the two groups (Frequency = 20 (9.66), 44 (5.39%), χ2 = 5.154, p < 0.05). Regarding human rights-based well-being, no significant difference was found between persons with mental health conditions or psychosocial disabilities and persons with other disabilities. However, the human rights-based well-being of women with mental health conditions or psychosocial disabilities was significantly worse than that of women with other types of disabilities. Concrete and day-to-day human rights challenges in several areas in addition to inaccessibility to various services may have contributed to the human rights challenges encountered by women with mental health conditions or psychosocial disabilities. De-stigmatization of women with mental health conditions or psychosocial disabilities, the implementation of awareness-raising campaigns on various levels, and developing capacity of women with mental health conditions or psychosocial disabilities on how to protect their own rights may help improve the status quo.
An open-source system for efficient clinical trial support: The COMET study experience
Authors: Clutton Jonathan , Montgomery Robert Neal , Mudaranthakam Dinesh Pal , Blocker Erin M. , Shaw Ashley R. , Szabo Reed Amanda N. , Vidoni Eric D.
Published: November 2023

Exercise clinical trials are complex, logistically burdensome, and require a well-coordinated multi-disciplinary approach. Challenges include managing, curating, and reporting on many disparate information sources, while remaining responsive to a variety of stakeholders. The Combined Exercise Trial (COMET, NCT04848038) is a one-year comparison of three exercise modalities delivered in the community. Target enrollment is 280 individuals over 4 years. To support rigorous execution of COMET, the study team has developed a suite of scripts and dashboards to assist study stakeholders in each of their various functions. The result is a highly automated study system that preserves rigor, increases communication, and reduces staff burden. This manuscript describes system considerations and the COMET approach to data management and use, with a goal of encouraging further development and adaptation by other study teams in various fields.
Type of anesthesia for cancer resection surgery: No differential impact on cancer recurrence in mouse models of breast cancer
Authors: Dubowitz Julia , Ziegler Alexandra I. , Beare Richard , Jost-Brinkmann Fabian , Walker Adam K. , Gillis Ryan D. , Chang Aeson , Chung Ni-Chun , Martin Olga A. , Hollande Frédéric , Riedel Bernhard , Sloan Erica K.
Published: November 2023

Background

Surgery is essential for curative treatment of solid tumors. Evidence from recent retrospective clinical analyses suggests that use of propofol-based total intravenous anesthesia during cancer resection surgery is associated with improved overall survival compared to inhaled volatile anesthesia. Evaluating these findings in prospective clinical studies is required to inform definitive clinical guidelines but will take many years and requires biomarkers to monitor treatment effect. Therefore, we examined the effect of different anesthetic agents on cancer recurrence in mouse models of breast cancer with the overarching goal of evaluating plausible mechanisms that could be used as biomarkers of treatment response.

Methods

To test the hypothesis that volatile anesthesia accelerates breast cancer recurrence after surgical resection of the primary tumor, we used three mouse models of breast cancer. We compared volatile sevoflurane anesthesia with intravenous propofol anesthesia and used serial non-invasive bioluminescent imaging to track primary tumor recurrence and metastatic recurrence. To determine short-term perioperative effects, we evaluated the effect of anesthesia on vascular integrity and immune cell changes after surgery in animal models.

Results

Survival analyses found that the kinetics of cancer recurrence and impact on survival were similar regardless of the anesthetic agent used during cancer surgery. Vascular permeability, immune cell infiltration and cytokine profiles showed no statistical difference after resection with inhaled sevoflurane or intravenous propofol anesthesia.

Conclusions

These preclinical studies found no evidence that choice of anesthetic agent used during cancer resection surgery affected either short-term perioperative events or long-term cancer outcomes in mouse models of breast cancer. These findings raise the possibility that mouse models do not recapitulate perioperative events in cancer patients. Nonetheless, the findings suggest that future evaluation of effects of anesthesia on cancer outcomes should focus on cancer types other than breast cancer.
A study on neural changes induced by sauna bathing: Neural basis of the “totonou” state
Authors: Chang Ming , Ibaraki Takuya , Naruse Yasushi , Imamura Yasuhiko
Published: November 2023

Saunas are becoming increasingly popular worldwide, being an activity that promotes relaxation and health. Intense feelings of happiness have been reported shortly after enjoying a hot sauna and cold water, what is known in Japan as the “totonou” state. However, no research has investigated what occurs in the brain during the “totonou” state. In the present study, participants underwent a sauna phase, consisting of three sets of alternating hot sauna, cold water, and rest. We elucidated changes in brain activity and mood in the “totonou” state by measuring and comparing brain activity and emotional scales before and after the sauna phase and during the rest phase in each set. We found significant increases in theta and alpha power during rest and after the sauna phase compared to before the sauna phase. Moreover, in an auditory oddball task, the p300 amplitude decreased significantly and MMN amplitude increased significantly after the sauna phase. The increase in MMN indicates higher activation of the pre-attentional auditory process, leading to a decrease in attention-related brain activity P300. Hence, the brain reaches in a more efficient state. Further, the response time in behavioral tasks decreased significantly. In addition, the participants’ subjective responses to the questionnaire showed significant changes in physical relaxation and other indicators after being in the sauna. Finally, we developed an artificial intelligence classifier, obtaining an average accuracy of brain state classification of 88.34%. The results have potential for future application.
Parasitism rate differs between herbivore generations in the univoltine, but not bivoltine, range
Authors: Gaytán Álvaro , Drobyshev Igor , Klisho Tatiana , Gotthard Karl , Tack Ayco J. M.
Published: November 2023

With climate change, plant-feeding insects increase their number of annual generations (voltinism). However, to what degree the emergence of a new herbivore generation affects the parasitism rate has not been explored. We performed a field experiment to test whether the parasitism rate differs between the first and the second generations of a specialist leaf miner (Tischeria ekebladella), both in the naturally univoltine and bivoltine parts of the leaf miner’s distribution. We found an interactive effect between herbivore generation and geographical range on the parasitism rate. The parasitism rate was higher in the first compared to the second host generation in the part of the range that is naturally univoltine, whereas it did not differ between generations in the bivoltine range. Our experiment highlights that shifts in herbivore voltinism might release top-down control, with potential consequences for natural and applied systems.
Synthesis and analyses of injectable fluoridated-bioactive glass hydrogel for dental root canal sealing
Authors: Irshad Nadia , Jahanzeb Noureen , Alqasim Alanood , Bousaleh Raneem , Almehrij Maha , Ghafoor Sarah , Nawaz Muhammad , Akhtar Sultan , Tufail Shah Asma , Khan Abdul Samad
Published: November 2023

This study aimed to synthesize fluoride-doped bioactive glass (F-BG) based thermo-sensitive injectable hydrogel for endodontic applications. The structural and phase analyses were done with Fourier Transform Infrared spectroscopy and X-ray Diffraction, respectively. The setting time of prepared injectable was investigated at 21°C (in the presence and absence of an ultrasonic scalar) and at 37°C. Flowability was tested according to ISO-6876:2012 specifications, whereas injectability was checked by extrusion method using 21-, 22-, and 23-gauge needles. The in vitro bio-adhesion and push-out bond strength were studied on days 7 and 90 and compared with the commercially available TotalFill®. The ion release profile was analyzed for up to 30 days with Inductively Coupled Plasma Optical Emission Spectroscopy. The fluoride release analysis was conducted periodically for up to 21 days in deionized water and artificial saliva using an ion-selective electrode. The final setting time at 21°C, 21°C+ultrasonic scalar, and 37°C were 38.66±3.21, 29.12±1.23, and 32±3.46 min, respectively. The flowability was 25±3.94 mm, and the injectability coefficient was ≥70.3 for 22, 21, and 57% in a 23-gauge needle. Fluoride release in deionized water was found to be significantly higher than in artificial saliva and increased with time. A significant difference in bond strength was found between days 7 and 90, where the strength was increased, and a new apatite layer was formed on the tooth surface. A rapid release of calcium, phosphate, and silicon ions was seen initially, whereby the continuous release of these ions was observed for up to 30 days. The prepared F-BG injectable hydrogel has shown promising results and has the potential to be used as an endodontic sealer.
Nrf1 is not a direct target gene of SREBP1, albeit both are integrated into the rapamycin-responsive regulatory network in human hepatoma cells
Authors: Liu Keli , Hu Shaofan , Qiu Lu , Wang Meng , Zhang Zhengwen , Sun Guiyin , Zhang Yiguo
Published: November 2023

The essential role of protein degradation by ubiquitin-proteasome system is exerted primarily for maintaining cellular protein homeostasis. The transcriptional activation of proteasomal genes by mTORC1 signaling depends on Nrf1, but whether this process is directly via SREBP1 remains elusive. In this study, our experiment evidence revealed that Nrf1 is not a direct target of SREBP1, although both are involved in the rapamycin-responsive regulatory networks. Closely scrutinizing two distinct transcriptomic datasets unraveled no significant changes in transcriptional expression of Nrf1 and almost all proteasomal subunits in either siSREBP2-silencing cells or SREBP1–∕–MEFs, when compared to equivalent controls. However, distinct upstream signaling to Nrf1 dislocation by p97 and its processing by DDI1/2, along with downstream proteasomal expression, may be monitored by mTOR signaling, to various certain extents, depending on distinct experimental settings in different types of cells. Our further evidence has been obtained from DDI1–∕–(DDI2insC) cells, demonstrating that putative effects of mTOR on the rapamycin-responsive signaling to Nrf1 and proteasomes may also be executed partially through a DDI1/2-independent mechanism, albeit the detailed regulatory events remain to be determined.
Facial asymmetry and midsagittal plane definition in 3D: A bias-free, automated method
Authors: Gkantidis Nikolaos , Opacic Jasmina , Kanavakis Georgios , Katsaros Christos , Halazonetis Demetrios
Published: November 2023

Symmetry is a fundamental biological concept in all living organisms. It is related to a variety of physical and social traits ranging from genetic background integrity and developmental stability to the perception of physical appearance. Within this context, the study of human facial asymmetry carries a unique significance. Here, we validated an efficient method to assess 3D facial surface symmetry by best-fit approximating the original surface to its mirrored one. Following this step, the midsagittal plane of the face was automatically defined at the midpoints of the contralateral corresponding vertices of the superimposed models and colour coded distance maps were constructed. The method was tested by two operators using facial models of different surface size. The results show that the midsagittal plane definition was highly reproducible (maximum error < 0.1 mm or°) and remained robust for different extents of the facial surface model. The symmetry assessments were valid (differences between corresponding bilateral measurement areas < 0.1 mm), highly reproducible (error < 0.01 mm), and were modified by the extent of the initial surface model. The present landmark-free, automated method to assess facial asymmetry and define the midsagittal plane of the face is accurate, objective, easily applicable, comprehensible and cost effective.
Disruption of international trade and its propagation through firm-level domestic supply chains: A case of Japan
Authors: Inoue Hiroyasu , Todo Yasuyuki
Published: November 2023

This study simulates how the disruption of imports from various regions affects the total production of the importer economy. We particularly incorporate the propagation of the economic effect through domestic supply chains using data on more than one million firms and four million supply chain ties in Japan. Our findings are summarized as follows. First, the negative effect of the disruption of intermediate imports grows exponentially as its duration and strength increase due to downstream propagation. Second, the propagation of the economic effect is substantially affected by the network topology of importers, such as the number of importers (affected nodes) and their degree of upstreamness in supply chains, whereas the effect of their degree centrality is heterogeneous depending on their degree of upstreamness. Finally, the negative effect of import disruption can be mitigated by the reorganization of domestic supply chains, even when conducted only among network neighbors. Our findings provide important policy and managerial implications for the achievement of more robust and resilient global supply chains.
Predictive factors of lymph node metastasis in papillary thyroid cancer
Authors: Song Woo Jin , Um In Chan , Kwon Sa Rang , Lee Jin Ho , Lim Hye Won , Jeong Yong Uk , Chung Seung Min , Moon Jun Sung , Yoon Ji Sung , Won Kyu Chang , Lee Hyoung Woo
Published: November 2023

This study aimed to evaluate factors that predict lymph node metastasis (LNM) in papillary thyroid cancer (PTC). This retrospective cross-sectional study compared the demographic, clinical, and ultrasonographic findings of patients with PTC with and without LNM. Subgroup analysis was conducted for micro-PTCs (<1 cm). Among total (n = 512; mean age, 47.3 ± 12.7 years) and micro-PTC patients (n = 312), 35.7% and 19.6% had LNM, respectively. Younger age, male sex, tumor size, bilaterality, and suspicious ultrasound features of the tumor were associated with LNM. In multiple logistic regression analysis, among all patients, age, tumor size, and extrathyroidal extension were independent risk factors for LNM (all p<0.05). In the micro-PTC subgroup, age, extrathyroidal extension, bilaterality of tumor, and presence of autoimmune thyroid disease were independent risk and protective factors for LNM (all p<0.05). In the receiver operating characteristic analysis, the accuracy of the multivariable logistic regression model for predicting LNM among all patients and micro-PTC was acceptable (area under the curve = 0.729 and 0.733, respectively). Age, sex, tumor size, and extrathyroidal extension can assist in predicting LNM in PTC patients. Additionally, the bilaterality of tumors and presence of autoimmune thyroid disease can assist in predicting LNM in micro-PTCs.
Canadian newspaper coverage on harm reduction featuring bereaved mothers: A mixed methods analysis
Authors: Morris Heather , Wild T. Cameron , Giovannoni Marina , Haines-Saah Rebecca , Koziel Jakob , Schulz Petra , Bwala Hauwa , Kunyk Diane , Bubela Tania , Hyshka Elaine
Published: November 2023

A growing body of evidence suggests that news media which includes a sympathetic portrayal of a mother bereaved by substance use can increase public support for harm reduction initiatives. However, the extent to which such news media coverage occurs in Canada is unknown, and research has not documented how the news media in Canada covers such stories. We undertook a mixed-method secondary analyses of 5681 Canadian newspaper articles on harm reduction (2000–2016). Quantitative analyses described the volume and content of harm reduction reporting featuring a mother whose child’s death was related to substance use while qualitative thematic analysis provided in-depth descriptions of the discourses underlying such news reporting. Newspaper articles featuring a mother whose child’s death was related to substance use were rarely published (n = 63; 1.1% of total harm reduction media coverage during the study period). Deductive content analysis of these 63 texts revealed that coverage of naloxone distribution (42.9%) and supervised drug consumption services (28.6%) were prioritized over other harm reduction services. Although harm reduction (services or policies) were advocated by the mother in most (77.8%) of these 63 texts, inductive thematic analysis of a subset (n = 52) of those articles revealed that mothers’ advocacy was diminished by newspaper reporting that emphasized their experiences of grief, prioritized individual biographies over structural factors contributing to substance use harms, and created rhetorical divisions between different groups of people who use drugs (PWUD). Bereaved mothers’ advocacy in support of harm reduction programs and services may be minimized in the process of reporting their stories for newspaper readers. Finding ways to report bereaved mothers’ stories in ways that are inclusive of all PWUD while highlighting the role of broad, structural determinants of substance use has the potential to shift public opinion and government support in favour of these life-saving services.
Soft tissue prediction in orthognathic surgery: Improving accuracy by means of anatomical details
Authors: Ruggiero Federica , Borghi Alessandro , Bevini Mirko , Badiali Giovanni , Lunari Ottavia , Dunaway David , Marchetti Claudio
Published: November 2023

Three-dimensional virtual simulation of orthognathic surgery is now a well-established method in maxillo-facial surgery. The commercial software packages are still burdened by a consistent imprecision on soft tissue predictions. In this study, the authors produced an anatomically detailed patient specific numerical model for simulation of soft tissue changes in orthognathic surgery. Eight patients were prospectively enrolled. Each patient underwent CBCT and planar x-rays prior to surgery and in addition received an MRI scan. Postoperative soft-tissue change was simulated using Finite Element Modeling (FEM) relying on a patient-specific 3D models generated combining data from preoperative CBCT (hard tissue) scans and MRI scans (muscles and skin). An initial simulation was performed assuming that all the muscles and the other soft tissue had the same material properties (Homogeneous Model). This model was compared with the postoperative CBCT 3D simulation for validation purpose. Design of experiments (DoE) was used to assess the effect of the presence of the muscles considered and of their variation in stiffness. The effect of single muscles was evaluated in specific areas of the midface. The quantitative distance error between the homogeneous model and actual patient surfaces for the midface area was 0.55 mm, standard deviation 2.9 mm. In our experience, including muscles in the numerical simulation of orthognathic surgery, brought an improvement in the quality of the simulation obtained.
Evaluating the cost of simplicity in score building: An example from alcohol research
Authors: Rousson Valentin , Trächsel Bastien , Iglesias Katia , Baggio Stéphanie
Published: November 2023

Building a score from a questionnaire to predict a binary gold standard is a common research question in psychology and health sciences. When building this score, researchers may have to choose between statistical performance and simplicity. A practical question is to what extent it is worth sacrificing the former to improve the latter. We investigated this research question using real data, in which the aim was to predict an alcohol use disorder (AUD) diagnosis from 20 self-reported binary questions in young Swiss men (n = 233, mean age = 26). We compared the statistical performance using the area under the ROC curve (AUC) of (a) a “refined score” obtained by logistic regression and several simplified versions of it (“simple scores”): with (b) 3, (c) 2, and (d) 1 digit(s), and (e) a “sum score” that did not allow negative coefficients. We used four estimation methods: (a) maximum likelihood, (b) backward selection, (c) LASSO, and (d) ridge penalty. We also used bootstrap procedures to correct for optimism. Simple scores, especially sum scores, performed almost identically or even slightly better than the refined score (respective ranges of corrected AUCs for refined and sum scores: 0.828–0.848, 0.835–0.850), with the best performance been achieved by LASSO. Our example data demonstrated that simplifying a score to predict a binary outcome does not necessarily imply a major loss in statistical performance, while it may improve its implementation, interpretation, and acceptability. Our study thus provides further empirical evidence of the potential benefits of using sum scores in psychology and health sciences.
Investigating social determinants of child health and their implications in reducing pediatric traumatic injury: A framework and 17-year retrospective case-control study protocol
Authors: Goodon Hunter , Gawaziuk Justin , Comaskey Brenda , Afifi Tracie O. , Château Dan , Brownell Marni , Sareen Jitender , Morgan Cora , Logsetty Sarvesh , Spiwak Rae
Published: November 2023

Introduction

Traumatic physical injuries are the number one cause of hospitalization and death among children in Canada. The majority of these injuries are preventable. The burden from injury can be reduced through prevention programs tailored to at-risk groups, however, existing research does not provide a strong explanation of how social factors influence a child’s risk of injury. We propose a theoretical framework to better understand social factors and injury in children and will examine the association between these social factors and physical traumatic injury in children using large population-wide data.

Methods and analysis

We will examine data from 11,000 children hospitalized for traumatic physical injury and 55,000 matched uninjured children by linking longitudinal administrative and clinical data contained at the Manitoba Centre for Health Policy. We will examine 14 social determinants of child health measures from our theoretical framework, including receipt of income assistance, rural/urban status, socioeconomic status, children in care, child mental disorder, and parental factors (involvement with criminal justice system, education, social housing, immigration status, high residential mobility, mother’s age at first birth, maternal Axis I mental disorder, maternal Axis II mental disorder and maternal physical disorder) to identify groups and periods of time when children are at greatest risk for traumatic physical injury. A conditional multivariable logistic regression model will be calculated (including all social determinant measures) to determine odds ratios and adjusted odds ratios (95% confidence interval) for cases (injured) and controls (non-injured).

Ethics and dissemination

Health Information Privacy Committee (HIPC No. 2017/2018-75) and local ethics approval (H2018-123) were obtained. Once social measures have been identified through statistical modelling, we will determine how they fit into a Haddon matrix to identify appropriate areas for intervention. Knowing these risk factors will guide decision-makers and health policy.
Stability analysis of nonlinear localized modes in the coupled Gross-Pitaevskii equations with P T -symmetric Scarf-II potential
Authors: Zhang Jia-Rui , Wang Xia
Published: November 2023

We study the nonlinear localized modes in two-component Bose-Einstein condensates with parity-time-symmetric Scarf-II potential, which can be described by the coupled Gross-Pitaevskii equations. Firstly, we investigate the linear stability of the nonlinear modes in the focusing and defocusing cases, and get the stable and unstable domains of nonlinear localized modes. Then we validate the results by evolving them with 5% perturbations as an initial condition. Finally, we get stable solitons by considering excitations of the soliton via adiabatical change of system parameters. These findings of nonlinear modes can be potentially applied to physical experiments of matter waves in Bose-Einstein condensates.