bluuebunny/crossref_metadata_2025 huggingface dataset:
Constructing metagenome-assembled genomes for almost all components in a real bacterial consortium for binning benchmarking
Authors: Wu Ziyao , Wang Yuxiao , Zeng Jiaqi , Zhou Yizhuang
Published: November 2022

Background

So far, a lot of binning approaches have been intensively developed for untangling metagenome-assembled genomes (MAGs) and evaluated by two main strategies. The strategy by comparison to known genomes prevails over the other strategy by using single-copy genes. However, there is still no dataset with all known genomes for a real (not simulated) bacterial consortium yet.

Results

Here, we continue investigating the real bacterial consortium F1RT enriched and sequenced by us previously, considering the high possibility to unearth all MAGs, due to its low complexity. The improved F1RT metagenome reassembled by metaSPAdes here utilizes about 98.62% of reads, and a series of analyses for the remaining reads suggests that the possibility of containing other low-abundance organisms in F1RT is greatly low, demonstrating that almost all MAGs are successfully assembled. Then, 4 isolates are obtained and individually sequenced. Based on the 4 isolate genomes and the entire metagenome, an elaborate pipeline is then in-house developed to construct all F1RT MAGs. A series of assessments extensively prove the high reliability of the herein reconstruction. Next, our findings further show that this dataset harbors several properties challenging for binning and thus is suitable to compare advanced binning tools available now or benchmark novel binners. Using this dataset, 8 advanced binning algorithms are assessed, giving useful insights for developing novel approaches. In addition, compared with our previous study, two novel MAGs termed FC8 and FC9 are discovered here, and 7 MAGs are solidly unearthed for species without any available genomes.

Conclusion

To our knowledge, it is the first time to construct a dataset with almost all known MAGs for a not simulated consortium. We hope that this dataset will be used as a routine toolkit to complement mock datasets for evaluating binning methods to further facilitate binning and metagenomic studies in the future.
CD19+CD24hiCD38hi regulatory B cells deficiency revealed severity and poor prognosis in patients with sepsis
Authors: Wang Chunmei , Xu Huihui , Gao Rui , Leng Fengying , Huo Fangjie , Li Yinzhen , Liu Siting , Xu Mingzheng , Bai Jianwen
Published: November 2022

Background

Sepsis still remains a major challenge in intensive care medicine with unacceptably high mortality among patients with septic shock. Due to current limitations of human CD19+CD24hiCD38hiBreg cells (Bregs) studies among sepsis, here, we tried to evaluate Bregs in severity and prognostic value in patients with sepsis.

Methods

Peripheral blood from 58 patients with sepsis and 22 healthy controls was analyzed using flow cytometry to evaluate the frequency and number of Bregs. All cases were divided into non-survived or survived group after 28 days followed up. Spearman's correlation analysis was performed on Bregs frequency and clinical indices. The area under the curve was acquired using the receiver operating characteristic analysis to assess the sensitivity and specificity of Bregs for outcome of sepsis. Survival curve analysis and binary logistic regression were applied to estimate the value of Bregs in prognosis among cases with sepsis.

Results

Sepsis patients had decreased proportions and number of Bregs. Sepsis patients with low frequency of Bregs were associated with an increased risk of septic shock. Bregs frequency is inversely associated with lactate, SOFA, and APACHE II and positively correlated with Tregs frequency. Low levels of Bregs closely correlated with septic outcomes. Numbers of Bregs were prediction factors for poor prognosis.

Conclusions

Frequency and number of Bregs decreased, and Bregs deficiency revealed poor prognosis in patients with sepsis.
Mechanism of LSD1 in oxygen-glucose deprivation/reoxygenation-induced pyroptosis of retinal ganglion cells via the miR-21-5p/NLRP12 axis
Authors: Yu Xiuling , Niu Tongtong , Liu Chi
Published: November 2022

Background

Retinal ganglion cells (RGCs) are important retinal neurons that connect visual receptors to the brain, and lysine-specific demethylase 1 (LSD1) is implicated in the development of RGCs. This study expounded the mechanism of LSD1 in oxygen-glucose deprivation/reoxygenation (OGD/R)-induced pyroptosis of RGCs.

Methods

Mouse RGCs underwent OGD/R exposure, and then RGC viability was examined using the cell counting kit-8 method. The mRNA levels of Caspase 1, the protein levels of NOD-like receptor family pyrin domain-containing 3 (NLRP3), N-terminal fragment of gasdermin D (GSDMD-N), and cleaved-Caspase1, and the concentrations of interleukin (IL)-1β and IL-18 were respectively examined. Subsequently, LSD1 expression was intervened to explore the underlying effect of LSD1 on OGD/R-induced pyroptosis of RGCs. Afterwards, the enrichments of LSD1 and histone H3 lysine 4 methylation (H3K4me) 1/2 on the microRNA (miR)-21-5p promoter were determined using chromatin-immunoprecipitation assay. And the binding interaction between miR-21-5p and NLRP12 was detected using dual-luciferase and RNA pull-down assays. Finally, the effects of miR-21-5p/NLRP12 on LSD1-mediated pyroptosis of RGCs were verified through functional rescue experiments.

Results

OGD/R treatment increased pyroptosis of RGCs and LSD1 expression. Silencing LSD1 declined levels of Caspase 1 mRNA, NLRP3, GSDMD-N, cleaved-Caspase1, IL-1β, and IL-18 and limited pyroptosis of OGD/R-treated RGCs. Mechanically, LSD1 suppressed miR-21-5p expression via demethylation of H3K4me2 on the miR-21-5p promoter to hamper the binding of miR-21-5p to NLRP12, and thereby increased NLRP12 expression. Silencing miR-21-5p or overexpressing NLRP12 facilitated OGD/R-induced pyroptosis of RGCs.

Conclusion

LSD1-mediated demethylation of H3K4me2 decreased miR-21-5p expression to increase NLRP12 expression, promoting pyroptosis of OGD/R-treated RGCs.
Determinants of therapy failure among adults on first-line antiretroviral therapy in Asmara, Eritrea: a multicenter retrospective matched case–control study
Authors: Mengistu Samuel Tekle , Ghebremeskel Ghirmay Ghebrekidan , Ghebrat Hermon Berhe , Achila Oliver Okoth , Yohannes Nahom Asmerom , Ghebrenegus Amon Solomon , Wendmhuney Filmon Ghebretsadik , Yeibyo Naod , Andegiorgish Amanuel Kidane , Mesfin Araia Berhane , Leake Negassi
Published: November 2022

Background

Information on treatment failure (TF) in People living with HIV in a data-poor setting is necessary to counter the epidemic of TF with first-line combined antiretroviral therapies (cART) in sub-Saharan Africa (SSA). In this study, we examined the risk factors associated with TF in Asmara, Eritrea from 2001 to 2020.

Methods

A multicenter, retrospective 1:2 matched (by age and gender) case–control study was conducted in four major hospitals in Asmara, Eritrea on adults aged ≥ 18 years who were on treatment for at least 6 months. Cases were patients who fulfills at least one of the WHO therapy failure criterion during the study period. Controls were randomly selected patients on first-line treatment and plasma viral load < 1000 copies/ml in their latest follow-up measurement. Multivariable logistic regression analysis was conducted to identify risk factors for TF. All P-values were 2-sided and the level of significance was set at P < 0.05 for all analyses.

Results

Of the 1068 participants (356 cases; 712 controls), 585 (54.7%) were females. The median age at treatment initiation was 46 years [interquartile range (IQR): 39–51]. Median time to combined antiretroviral therapy (cART) failure was 37 months (IQR = 24–47). In the multivariate analysis, factors associated with increased likelihood of TF included initial nucleoside reverse transcriptase inhibitors (NRTI) backbone (Zidovudine + Lamivudine (AZT + 3TC): adjusted odds ratio (aOR) = 2.70, 95% Confidence interval (CI): 1.65–4.41, P-value < 0.001), (Abacavir + lamivudine (ABC + 3TC): aOR = 4.73, 95%CI: 1.18–18.92, P-value = 0.028], and (Stavudine + Lamivudine (D4T + 3TC): aOR = 5.00; 95% CI: 3.03–8.20, P-value < 0.001) in comparison to Emtricitabine and Tenofovir diproxil fumarate (FTC + TDF). Additional associations included prior exposure to cART (aOR = 2.28, 95%CI: 1.35–3.86; P- value = 0.002), record of sub-optimal drug adherence (aOR = 3.08, 95%CI: 2.22–4.28; P < 0.001), ambulatory/bedridden at presentation (aOR = 1.61, 95%CI: 1.12–4.28; P-value = 0.010), presence of comorbidities (aOR = 2.37; 95%CI: 1.36–4.10, P-value = 0.002), duration of cART (< 5 years: aOR: 5.90; 95% CI: 3.95–8.73, P-value < 0.001), and use of SMX-TMP prophylaxis (aOR = 2.00, 95%CI, 1.44–2.78, P-value < 0.001).

Conclusion

Our findings underscore the importance of optimizing cART adherence, diversification of cART regimens, and interventions directed at enhancing early HIV diagnosis, prompt initiations of treatment, and improved patient-focused monitoring of treatment response.
A case of Kernohan-Woltman notch phenomenon caused by an epidural hematoma: the diagnostic and prognostic value of PET/CT imaging
Authors: Lin Yuliang , Chen-Lung Chou Alan , Lin Xiangming , Wu Zhende , Ju Qichao , Li Yuexuan , Ye Zulong , Zhang Bo
Published: November 2022

Background

Kernohan-Woltman notch phenomenon (KWNP) classically occurs when a lesion causes compression of the contralateral cerebral peduncle against the tentorium, resulting in ipsilateral hemiparesis. It has been studied clinically, radiologically and electrophysiologically which all confirmed to cause false localizing motor signs. Here, we demonstrate the potential use of fluorine-18 fluorodeoxyglucose (18 F-FDG) positron emission tomography/computed tomography (PET/CT) to identify KWNP caused by an epidural hematoma.

Case presentation

A 29-year-old male patient post right-sided traumatic brain injury presenting with persistent ipsilateral hemiparesis. Patient underwent decompressive craniotomy and intracranial hematoma evacuation. Brain magnetic resonance imaging in the postoperative period showed a subtle lesion in the left cerebral peduncle. PET/CT was performed to exclude early brain tumor and explain his ipsilateral hemiparesis. PET/CT imaging demonstrated a focal region of intense 18 F-FDG uptake in the left cerebral peduncle. Throughout the treatment in outpatient neurorehabilitation unit, the patient exhibited a gradual recovery of his right hemiparesis.

Conclusion

In our case report, for the first time, PET/CT offered microstructural and functional confirmation of KWNP. Moreover, our case suggests that 18 F-FDG PET/CT may serve as an important reference for the probability of functional recovery.
Skilled antenatal care services utilisation in sub-Saharan Africa: a pooled analysis of demographic and health surveys from 32 countries
Authors: Dickson Kwamena Sekyi , Okyere Joshua , Ahinkorah Bright Opoku , Seidu Abdul-Aziz , Salihu Tarif , Bediako Vincent , Owusu Bernard Afriyie , Budu Eugene , Agbemavi Wonder , Edjah Jane Odurowaah , Darteh Eugene Kofuor Maafo
Published: November 2022

Background

Each day, an estimated 800 women die from preventable pregnancy and childbirth related complications, where 99% of these avoidable deaths happen in low-and middle-income countries. Skilled attendance during antenatal care (ANC) plays a role in reducing maternal and child mortality. However, the factors that predict the utilisation of skilled ANC services in sub-Saharan Africa (SSA) remains sparsely investigated. Therefore, we examined women’s utilisation of skilled ANC services in SSA.

Methods

The research used pooled data from the most recent Demographic and Health Surveys conducted in 32 countries in SSA between January 1, 2010, and December 31, 2019. Binary logistic regression was used to examine the predictors of skilled ANC services utilisation. The results are presented as crude and adjusted odds ratios (aOR) with 95% confidence interval (CI).

Results

The prevalence of skilled ANC services utilisation in SSA was 76.0%, with the highest and lowest prevalence in Gambia (99.2%) and Burundi (8.4%), respectively. Lower odds of ANC from skilled providers was found among women aged 45–49 compared to those aged 20–24 (aOR = 0.86, CI = 0.79–0.94); widowed women compared to married women (aOR = 0.84, CI = 0.72–0.99); women who consider getting permission to visit the health facility as a big problem compared to those who consider that as not a big problem (aOR = 0.74, CI = 0.71–0.77); women who consider getting money needed for treatment as not a big problem compared to those who consider that as a big problem (aOR = 0.84, CI = 0.72–0.99); and women who consider distance to the health facility as a big problem compared to those who consider that as not a big problem (aOR = 0.75, CI = 0.72–0.77).

Conclusion

SSA has relatively high prevalence of skilled ANC services utilisation, however, there are substantial country-level disparities that need to be prioritised. Increasing maternal reproductive age being widowed and far distance to health facility were factors that predicted lower likelihood of skilled ANC services utilisation. There is, therefore, the need to intensify female formal education, invest in community-based healthcare facilities in rural areas and leverage on the media in advocating for skilled ANC services utilisation.
Antiretroviral therapy non-adherence among children living with HIV in Dire Dawa, Eastern Ethiopia: a case-control study
Authors: Mengesha Melkamu Merid , Embibel Mulugeta , Gobena Tesfaye , Tunje Abayneh , Jerene Degu , Hallström Inger Kristensson
Published: November 2022

Background:

In 2018, nearly 90% of the global children living with human immunodeficiency virus (HIV) were in sub-Saharan Africa (SSA). Compared to the adult population, antiretroviral therapy (ART) coverage among children was limited. However, adherence remained a problem among children though they had limited access to ART. This study was conducted to identify the risk factors of non-adherence to ART among children aged 6 to 17 years.

Methods:

This case-control study was conducted in 2020 using data obtained from clinical record reviews and self-reported data from 272 caregivers of HIV-infected children aged 6–17 years. Cases and controls represented children with poor versus children with good adherence to ART, respectively. Good adherence was defined based on a past 30-day physician adherence evaluation of taking ≥ 95% of the prescribed doses. Binary logistic regression was used to identify factors associated with non-adherence to ART. All statistical tests are defined as statistically significant at P-values < 0.05.

Results:

Of the 272 children, for whom data were obtained, 78 were cases and 194 were controls; females accounted for 56.3%, 32% attended secondary school, and for 83.1%, the reporting caregivers were biological parents. Non-adherent children had higher odds of association with the following risk factors: a caregiver who is a current substance user (aOR = 2.87, 95% CI: 1.44, 5.71), using AZT-and ABC-based regimen compared to the TDF-regimen (AZT-based, aOR = 4.12, 95% CI: 1.43, 11.86; ABC-based, aOR = 5.58, 95% CI: 1.70, 18.30), and had an increase in viral load from baseline compared to those remained undetectable (remained at or decreased to < 1000, aOR = 4.87, 95% CI: 1.65, 14.33; remained at ≥ 1000, aOR = 9.30, 95% CI: 3.69, 23.46). In contrast, non-adherent children had 66% lower odds of being at early adolescent age compared to 6–9 years old (10–14 years, aOR = 0.34, 95% CI: 0.12, 0.99) and had 70% lower odds of being aware of their HIV status (aOR = 0.30, 95% CI: 0.13, 0.73).

Conclusion:

Technical support to caregivers to build disclosure self-efficacy, identifying the appropriate regimen for children, counseling on viral load suppression on subsequent visits, and helping caregivers avoid or reduce substance use may help improve the problem of children’s non-adherence to ART.
Utility of illness symptoms for predicting COVID-19 infections in children
Authors: Zhou Geena Y. , Penwill Nicole Y. , Cheng Grace , Singh Prachi , Cheung Ann , Shin Minkyung , Nguyen Margaret , Mittal Shalini , Burrough William , Spad Mia-Ashley , Bourne Sarah , Bardach Naomi S. , Perito Emily R.
Published: November 2022

Background

The Centers for Disease Control and Prevention and the American Academy of Pediatrics recommend that symptomatic children remain home and get tested to identify potential coronavirus disease 2019 (COVID-19) cases. As the pandemic moves into a new phase, approaches to differentiate symptoms of COVID-19 versus other childhood infections can inform exclusion policies and potentially prevent future unnecessary missed school days.

Methods

Retrospective analysis of standardized symptom and exposure screens in symptomatic children 0–18 years tested for SARS-CoV-2 at three outpatient sites April to November 2020. Likelihood ratios (LR), number needed to screen to identify one COVID-19 case, and estimated missed school days were calculated.

Results

Of children studied (N = 2,167), 88.9% tested negative. Self-reported exposure to COVID-19 was the only factor that statistically significantly increased the likelihood of a positive test for all ages (Positive LR, 5–18 year olds: 5.26, 95% confidence interval (CI): 4.37–6.33; 0–4 year olds: 5.87, 95% CI: 4.67–7.38). Across ages 0–18, nasal congestion/rhinorrhea, sore throat, abdominal pain, and nausea/vomiting/diarrhea were commonly reported, and were either not associated or had decreased association with testing positive for COVID-19. The number of school days missed to identify one case of COVID-19 ranged from 19 to 48 across those common symptoms.

Conclusions

We present an approach for identifying symptoms that are non-specific to COVID-19, for which exclusion would likely lead to limited impact on school safety but contribute to school-days missed. As variants and symptoms evolve, students and schools could benefit from reconsideration of exclusion and testing policies for non-specific symptoms, while maintaining testing for those who were exposed.
Evaluating the effect of drunk driving on fatal injuries among vulnerable road users in Taiwan: a population-based study
Authors: Lin Hui-An , Chan Cheng-Wei , Wiratama Bayu Satria , Chen Ping-Ling , Wang Ming-Heng , Chao Chung-Jen , Saleh Wafaa , Huang Hung-Chang , Pai Chih-Wei
Published: November 2022

Background

Most studies have focused on injuries sustained by intoxicated drivers themselves, but few have examined the effect of drunk driving on injury outcomes among VRUs (vulnerable road users) in developing countries. This study aims to evaluate the effect of drunk driving on fatal injuries among VRUs (pedestrians, cyclists, or motorcyclists).

Methods

The data were extracted from the National Taiwan Traffic Crash Dataset from January 1, 2011, to December 31, 2019. Crashes involving one motorized vehicle and one VRU were considered. This study examines the effect of drunk driving by estimating multivariate logistic regression models of fatal injuries among VRUs after controlling for other variables.

Results

Among 1,416,168 casualties, the fatality rate of VRUs involved in drunk driving was higher than that of general road users (2.1% vs. 0.6%). Drunk driving was a significant risk factor for fatal injuries among VRUs. Other risk factors for fatal injuries among VRUs included VRU age ≥ 65 years (adjusted odds ratio [AOR]: 5.24, 95% confidence interval [CI]: 5.53–6.07), a nighttime accident (AOR: 4.52, 95% CI: 4.22–4.84), and being hit by a heavy-duty vehicle (AOR: 2.83, 95% CI: 2.26–3.55). Subgroup analyses revealed a linear relationship between driver blood alcohol concentration (BAC) and the risk of fatal injury among motorcyclists. Motorcyclists exhibited the highest fatality rate when they had a BAC ≤ 0.03% (AOR: 3.54, 95% CI: 3.08–4.08).

Conclusion

Drunk driving was associated with a higher risk of fatality for all VRUs. The risk of fatal injury among motorcyclists was linearly related to the BAC of the drunk drivers. Injuries were more severe for intoxicated motorcyclists, even those with BAC ≤ 0.03%, which is within the legal limit.
Surgery versus radiotherapy in octogenarians with stage Ia non‑small cell lung cancer: propensity score matching analysis of the SEER database
Authors: Ni Lianfang , Lin Gang , Zhang Zhigang , Sun Dan , Liu Zhonghui , Liu Xinmin
Published: November 2022

Objectives

To compare overall survival (OS) and cancer-specific survival (CSS) outcomes of surgery with radiotherapy in octogenarians with stage Ia non-small cell lung cancer (NSCLC).

Materials and methods

Patients aged ≥ 80 years with clinical stage Ia (T1N0M0) NSCLC between 2012 and 2017 were identified from the population-based Surveillance, Epidemiology, and End Results (SEER) database. Patients were assigned into surgery and radiotherapy groups. Multivariate Cox regression analysis was used to identify survival-associated factors. Treatment groups were adjusted by propensity score matching (PSM) analysis while OS and CSS outcomes were compared among groups by Kaplan–Meier analysis.

Results

A total of 1641 patients were identified, with 46.0% in the surgical group and 54.0% in the radiotherapy group. Compared to surgery, radiotherapy-treated patients were older, later diagnosed, had more often unmarried, more squamous cell carcinoma, more unknown grade and increased tumor sizes. Radiotherapy was associated with a significantly worse OS, compared to surgery (hazard ratio 2.426; 95% CI 2.003–2.939; P < .001). After PSM, OS (P < 0.001) and CSS (P < 0.001) were higher in the surgery group. The 1-, 3-, and 5-year OS rates of surgical and radiotherapy group were 90.0%, 76.9%, 59.9%, and 86.0%, 54.3%, 28.0%, respectively. The 1-, 3-, and 5-year CSS rates of surgical and radiotherapy group were 94.5%, 86.1%, 78.0% and 90.7%, 74.5%, 61.0%, respectively. There were no survival differences between the matched surgery without lymph node examination (LNE) and radiotherapy group, as well as between the matched surgery and radiotherapy who were recommended but refused surgery group.

Conclusions

In octogenarians with stage Ia NSCLC, surgery with lymph node dissection offers better OS and CSS outcomes than radiotherapy.
An evaluation of lower urinary tract symptoms in diabetic patients: a cross-sectional study
Authors: Qasrawi Hala , Tabouni Mahmoud , Almansour Sara W. , Ghannam Mohammad , Abdalhaq Amjad , Abushamma Faris , Koni Amer A. , Zyoud Sa’ed H.
Published: November 2022

Background

Lower urinary tract symptoms (LUTS) are common among diabetic patients and represent hidden and mysterious morbidity. The pathophysiology of LUTS among diabetes mellitus (DM) patients is multifactorial. Importantly, LUTS is known to cause physical and psychological distress. Thus, this study describes LUTS among DM patients, investigates factors that may associate with it, and assesses the possible relationship between LUTS and the quality of life of diabetics.

Methods

Over 6 months, data were collected from 378 diabetic patients in primary health care clinics. Demographic and clinical characteristics, Urogenital Distress Inventory-6 (UDI-6), and Incontinence Impact Questionnaire-7 (IIQ-7) were used to collect data. Univariate and multivariate analyses were performed.

Results

Three hundred seventy-eight participants were included in this study. (29.9%) were (58–67) years old. 49% were female. Half of the cohort was overweight, and a third were obese. 81% were Type 2 DM. Almost all of them are on medical treatment. A median score of 5.50 (2.00–8.00) for the UDI-6 scale and a median score of 5 (0.00–10.00) for the IIQ-7 scale were reported. Multiple linear regression models showed that residency (p = 0.038) and regular exercise (p = 0.001) were significantly and negatively correlated with the UDI-6 score, while female gender (p = 0.042), insulin use (p = 0.009) and the presence of comorbidities (p = 0.007) were positively correlated with this score. Furthermore, age (p = 0.040) and body mass index (BMI) (p < 0.001) were significantly and positively associated with the IIQ-7 score.

Conclusion

LUTS is significant morbidity among DM patients. Factors such as age, BMI, and co-morbidities exacerbate LUTS, which can be modified and controlled. On the other hand, regular exercise and weight loss strategies help diabetic patients to improve LUTS.
Development and evaluation of a virtual reality mechanical ventilation education program for nursing students
Authors: Lee Hanna , Han Jeong-Won
Published: November 2022

Background

Since COVID-19 limits safe clinical practice settings, virtual reality (VR) emerged as an alternative to practical education. Using VR simulation to learn mechanical ventilation is rare in nursing education.

Methods

This study developed a VR simulation program for mechanical ventilation care and evaluated its effects. We adopted a quasi-experiment design. Participants were fourth-year students across nursing colleges in South Korea.

Results

The interaction effect of the intervention time point and control group, to which the VR simulation program was applied, showed a significant difference in self-efficacy (F = 19.54, p < .001) and clinical reasoning capacity (F = 16.97, p < .001). Learning satisfaction of the experimental group was statistically significantly higher than that of the control group(F = 5.22, p = .026). The level of learning immersion (t = − 3.13, p = .003) and learning satisfaction (t = − 3.49, p = .001) were statistically significantly higher in the experimental group than in the control group.

Conclusion

These findings confirmed that the VR stimulation program for nursing students had a positive effect on their self-efficacy, clinical reasoning capacity, and learning satisfaction. Furthermore, it was effective in improving their nursing competence.
Astrocytes in CA1 modulate schema establishment in the hippocampal-cortical neuron network
Authors: Liu Shu , Wong Heung Yan , Xie Li , Iqbal Zafar , Lei Zhuogui , Fu Zhongqi , Lam Yuk Yan , Ramkrishnan Aruna Surendran , Li Ying
Published: November 2022

Background

Schema, a concept from cognitive psychology used to explain how new information is integrated with previous experience, is a framework of acquired knowledge within associative network structures as biological correlate, which allows new relevant information to be quickly assimilated by parallel cortical encoding in the hippocampus (HPC) and cortex. Previous work demonstrated that myelin generation in the anterior cingulate cortex (ACC) plays a critical role for dynamic paired association (PA) learning and consolidation, while astrocytes in ACC play a vital role in cognitive decision-making. However, circuit components and mechanism involving HPC-anterior cingulate cortex (ACC) during schema formation remain uncertain. Moreover, the correlation between HPC-ACC circuit and HPC astrocytic activity is unclear.

Results

Utilizing a paired association (PA) behavioral paradigm, we dynamically recorded calcium signals of CA1-ACC projection neurons and ACC neurons during schema formation. Depending on the characteristics of the calcium signals, three distinct stages of schema establishment process were identified. The recruitment of CA1-ACC network was investigated in each stage under CA1 astrocytes Gi pathway chemogenetic activation. Results showed that CA1-ACC projecting neurons excitation gradually decreased along with schema development, while ACC neurons revealed an excitation peak in the middle stage. CA1 astrocytic Gi pathway activation will disrupt memory schema development by reducing CA1-ACC projection neuron recruitment in the initial stage and prevent both CA1-ACC projection neurons and ACC neuron excitation in the middle stage. CA1 astrocytes Gi markedly suppress new PA assimilation into the established memory schema.

Conclusions

These results not only reveal the dynamic feature of CA1-ACC network during schema establishment, but also suggest CA1 astrocyte contribution in different stages of schema establishment.
ERF49 mediates brassinosteroid regulation of heat stress tolerance in Arabidopsis thaliana
Authors: Chen Xia , Xue Huidan , Zhu Liping , Wang Huiqin , Long Hao , Zhao Jun , Meng Funing , Liu Yunfei , Ye Yuan , Luo Xiaomin , Liu Zhi , Xiao Guanghui , Zhu Shengwei
Published: November 2022

Background

Heat stress is a major abiotic stress affecting the growth and development of plants, including crop species. Plants have evolved various adaptive strategies to help them survive heat stress, including maintaining membrane stability, encoding heat shock proteins (HSPs) and ROS-scavenging enzymes, and inducing molecular chaperone signaling. Brassinosteroids (BRs) are phytohormones that regulate various aspects of plant development, which have been implicated also in plant responses to heat stress, and resistance to heat in Arabidopsis thaliana is enhanced by adding exogenous BR. Brassinazole resistant 1 (BZR1), a transcription factor and positive regulator of BR signal, controls plant growth and development by directly regulating downstream target genes. However, the molecular mechanism at the basis of BR-mediated heat stress response is poorly understood. Here, we report the identification of a new factor critical for BR-regulated heat stress tolerance.

Results

We identified ERF49 in a genetic screen for proteins required for BR-regulated gene expression. We found that ERF49 is the direct target gene of BZR1 and that overexpressing ERF49 enhanced sensitivity of transgenic plants to heat stress. The transcription levels of heat shock factor HSFA2, heat stress-inducible gene DREB2A, and three heat shock protein (HSP) were significantly reduced under heat stress in ERF49-overexpressed transgenic plants. Transcriptional activity analysis in protoplast revealed that BZR1 inhibits ERF49 expression by binding to the promoter of ERF49. Our genetic analysis showed that dominant gain-of-function brassinazole resistant 1-1D mutant (bzr1-1D) exhibited lower sensitivity to heat stress compared with wild-type. Expressing ERF49-SRDX (a dominant repressor reporter of ERF49) in bzr1-1D significantly decreased the sensitivity of ERF49-SRDX/bzr1-1D transgenic plants to heat stress compared to bzr1-1D.

Conclusions

Our data provide clear evidence that BR increases thermotolerance of plants by repressing the expression of ERF49 through BZR1, and this process is dependent on the expression of downstream heat stress-inducible genes. Taken together, our work reveals a novel molecular mechanism mediating plant response to high temperature stress.
Clinical improvement of DM1 patients reflected by reversal of disease-induced gene expression in blood
Authors: van Cruchten Remco T. P. , van As Daniël , Glennon Jeffrey C. , van Engelen Baziel G. M. , ‘t Hoen Peter A. C. ,   the OPTIMISTIC consortium,   the ReCognitION consortium, Okkersen K , Jimenez-Moreno C , Wenninger S , Daidj F , Cumming S , Littleford R , Monckton D G , Lochmüller H , Catt M , Faber C G , Hapca A , Donnan P T , Gorman G , Bassez G , Schoser B , Knoop H , Treweek S , Wansink Derick G. , Impens Francis , Gabriels Ralf , Claeys Tine , Ravel-Chapuis Aymeric , Jasmin Bernard J. , Mahon Niamh , Nieuwenhuis Sylvia , Martens Lennart , Novak Petr , Furling Denis , Baak Arie , Gourdon Genevieve , MacKenzie Alex , Martinat Cecile , Neault Nafisa , Roos Andreas , Duchesne Elise , Salz Renee , Thompson Rachel , Baghdoyan Sandrine , Varghese Anu Mary , Blom Paul , Spendiff Sally , Manta Alexander
Published: November 2022

Background

Myotonic dystrophy type 1 (DM1) is an incurable multisystem disease caused by a CTG-repeat expansion in the DM1 protein kinase (DMPK) gene. The OPTIMISTIC clinical trial demonstrated positive and heterogenous effects of cognitive behavioral therapy (CBT) on the capacity for activity and social participations in DM1 patients. Through a process of reverse engineering, this study aims to identify druggable molecular biomarkers associated with the clinical improvement in the OPTIMISTIC cohort.

Methods

Based on full blood samples collected during OPTIMISTIC, we performed paired mRNA sequencing for 27 patients before and after the CBT intervention. Linear mixed effect models were used to identify biomarkers associated with the disease-causing CTG expansion and the mean clinical improvement across all clinical outcome measures.

Results

We identified 608 genes for which their expression was significantly associated with the CTG-repeat expansion, as well as 1176 genes significantly associated with the average clinical response towards the intervention. Remarkably, all 97 genes associated with both returned to more normal levels in patients who benefited the most from CBT. This main finding has been replicated based on an external dataset of mRNA data of DM1 patients and controls, singling these genes out as candidate biomarkers for therapy response. Among these candidate genes wereDNAJB12,HDAC5, andTRIM8, each belonging to a protein family that is being studied in the context of neurological disorders or muscular dystrophies. Across the different gene sets, gene pathway enrichment analysis revealed disease-relevant impaired signaling in, among others, insulin-, metabolism-, and immune-related pathways. Furthermore, evidence for shared dysregulations with another neuromuscular disease, Duchenne muscular dystrophy, was found, suggesting a partial overlap in blood-based gene dysregulation.

Conclusions

DM1-relevant disease signatures can be identified on a molecular level in peripheral blood, opening new avenues for drug discovery and therapy efficacy assessments.
Putative juvenile terrorists: the relationship between multiple traumatization, mental health, and expectations for reintegration among Islamic State recruited adolescent and young adult fighters
Authors: Mohammed Rezhna , Neuner Frank
Published: November 2022

Background

In several conflicts worldwide children are recruited as fighters in irregular forces. These children need to be reintegrated into the society after the conflict. However, concurrent to various reservations in the communities, the reintegration of former child soldiers is challenged by the fact that many of the affected children were indoctrinated by the armed group and traumatized through war events. Even several years after the defeat of the terrorist organization ISIS in Iraq, systematic efforts towards the reintegration of children who had been recruited by ISIS are notably absent.

Methods

we conducted clinical interviews with a sample of N = 59 adolescents and young adults who were incarcerated for terrorism in the prisons of the Kurdistan Region of Iraq to assess levels and types of trauma exposure, PTSD, depression, readiness to reintegrate and ongoing identification with ISIS.

Results

We found high levels of PTSD and depression that were associated with trauma exposure. The subjective readiness to reintegrate into the communities was associated with trauma exposure and was mediated by depression, even after controlling for the influence of ongoing identification with the armed group.

Conclusion

The study indicates that trauma-related mental ill-health should be considered in efforts to reintegrate young former terrorists.
Tuning gradient boosting for imbalanced bioassay modelling with custom loss functions
Authors: Boldini Davide , Friedrich Lukas , Kuhn Daniel , Sieber Stephan A.
Published: November 2022

While in the last years there has been a dramatic increase in the number of available bioassay datasets, many of them suffer from extremely imbalanced distribution between active and inactive compounds. Thus, there is an urgent need for novel approaches to tackle class imbalance in drug discovery. Inspired by recent advances in computer vision, we investigated a panel of alternative loss functions for imbalanced classification in the context of Gradient Boosting and benchmarked them on six datasets from public and proprietary sources, for a total of 42 tasks and 2 million compounds. Our findings show that with these modifications, we achieve statistically significant improvements over the conventional cross-entropy loss function on five out of six datasets. Furthermore, by employing these bespoke loss functions we are able to push Gradient Boosting to match or outperform a wide variety of previously reported classifiers and neural networks. We also investigate the impact of changing the loss function on training time and find that it increases convergence speed up to 8 times faster. As such, these results show that tuning the loss function for Gradient Boosting is a straightforward and computationally efficient method to achieve state-of-the-art performance on imbalanced bioassay datasets without compromising on interpretability and scalability.

Graphical Abstract
De novo and inherited variants in coding and regulatory regions in genetic cardiomyopathies
Authors: Vadgama Nirmal , Ameen Mohamed , Sundaram Laksshman , Gaddam Sadhana ,   Genomics England Research Consortium, Gifford Casey , Nasir Jamal , Karakikes Ioannis
Published: November 2022

Background

Cardiomyopathies are a leading cause of progressive heart failure and sudden cardiac death; however, their genetic aetiology remains poorly understood. We hypothesised that variants in noncoding regulatory regions and oligogenic inheritance mechanisms may help close the diagnostic gap.

Methods

We first analysed whole-genome sequencing data of 143 parent–offspring trios from Genomics England 100,000 Genomes Project. We used gene panel testing and a phenotype-based, variant prioritisation framework called Exomiser to identify candidate genes in trios. To assess the contribution of noncoding DNVs to cardiomyopathies, we intersected DNVs with open chromatin sequences from single-cell ATAC-seq data of cardiomyocytes. We also performed a case–control analysis in an exome-negative cohort, including 843 probands and 19,467 controls, to assess the association between noncoding variants in known cardiomyopathy genes and disease.

Results

In the trio analysis, a definite or probable genetic diagnosis was identified in 21 probands according to the American College of Medical Genetics guidelines. We identified novel DNVs in diagnostic-grade genes (RYR2, TNNT2, PTPN11, MYH7, LZR1, NKX2-5), and five cases harbouring a combination of prioritised variants, suggesting that oligogenic inheritance and genetic modifiers contribute to cardiomyopathies. Phenotype-based ranking of candidate genes identified in noncoding DNV analysis revealed JPH2 as the top candidate. Moreover, a case–control analysis revealed an enrichment of rare noncoding variants in regulatory elements of cardiomyopathy genes (p = .035, OR = 1.43, 95% Cl = 1.095–1.767) versus controls. Of the 25 variants associated with disease  (p< 0.5), 23 are novel and nine are predicted to disrupt transcription factor binding motifs.

Conclusion

Our results highlight complex genetic mechanisms in cardiomyopathies and reveal novel genes for future investigations.
Psychometric assessment of Persian translation of Yale Food Addiction Scale Version 2.0 (YFAS 2.0) in Iranian college students
Authors: Ghanbari Nikzad , Nooripour Roghieh , Firoozabadi Abbas , Var Tabassom Saeid Par , Wisniewski Pamela , Hosseini Seyed Ruhollah
Published: November 2022

Background

Food addiction at the individual level causes physical and mental health problems, impairs individuals' social functioning, and causes dysfunction in the family system. Therefore, a tool to identify this behavioral disorder is one of the health requirements of communities. This research aimed to investigate the psychometric assessment of the Persian translation of Yale Food Addiction Scale Version 2.0 (YFAS 2.0) in Iranian college students.

Method

This research was cross-sectional descriptive, and 451 students were selected by convenience sampling method. Yale Food Addiction Scale Version 2.0 (YFAS 2.0), Depression, Anxiety, and Stress Scale-21 (DASS-21), and Food Craving Questionnaire-Trait, reduced (FCQ-T-r) were used to collect data.

Results

The confirmatory factor analysis indicated that single-factor model provides a good fit to data (SRMR = 0.078; CFI = 0.94; NFI = 0.92; IFI = 0.94; RFI = 0.91; GFI = 0.90; RMSEA = 0.078). The YFAS's 2.0 positive correlations with three DASS-21 subscales ranged from 0.30 to 0.39, and Food Craving Questionnaire-Trait, reduced (FCQ-T-r) ranged from 0.58 to 0.72. All correlations were statistically significant, indicating acceptable convergent validity (P < 0.01).

Conclusion

The validity of the Persian questionnaire translation has been confirmed. Researchers and specialists can use this scale to diagnose food addiction for research or diagnostic purposes in Iranian society.
Bone scintigraphy outperformed anatomic images in frostbite injuries: a case report
Authors: Ronchi Brunela , Peña Gustavo Agustin , Carla Albertti
Published: November 2022

Frostbite is a localized cold thermal injury, as a result of tissue exposure to temperatures below freezing point for a prolonged period of time. The spectrum of injury is broad; thus, frostbite injuries may have deleterious effects with the possibility of losing part or whole extremities. We aim to present the case of a 38-year-old male patient evaluated with multiphase technetium-99m-methylene diphosphonate bone scintigraphy. This methodology may accelerate clinical management of frostbite injuries because it provides precise clinical-imaging correlation by determining the extent of injury and can accurately predict the level of amputation if required.
Automatic interpretive image-focusing analysis
Authors: Jennings Joseph , Clapp Robert , Araya-Polo Mauricio , Biondi Biondo
Published: November 2022

The focusing of a seismic image is directly linked to the accuracy of the velocity model. Therefore, a critical step in a seismic imaging workflow is to perform a focusing analysis on a seismic image to determine velocity errors. Although the offset/aperture-angle axis is frequently used for focusing analysis, the physical axes of seismic images tend to be ignored because the focusing analysis of geologic structures is highly interpretive and difficult to automate. We have developed an automatic data-driven approach using convolutional neural networks to automate image-focusing analysis. Using focused and unfocused geologic faults, our approach makes use of spatial and offset/angle focusing information to robustly estimate local focusing errors within seismic images. The application of our method to a 2D limited-aperture image from the Gulf of Mexico shows that it can correctly estimate local focusing errors within the image, while a traditional semblance-based approach fails. Additionally, the proposed approach has the added benefit of improving the interpretation of faults within the image.
Hilbert transform of unequally sampled data: Application to dispersion relations in magnetotellurics
Authors: Başokur Ahmet Tuğrul
Published: November 2022

The real and imaginary parts of the Fourier transform of a causal signal can be estimated from one another using the Hilbert transform. The numerical computation can be carried out by a fast Fourier transform or the convolution of the data with an appropriate Hilbert kernel. However, magnetotelluric (MT) data are unequally sampled because logarithmic frequency axes are conventionally used. A method has been developed for the Hilbert transformation of unequally sampled data and applied to the real and imaginary parts of the frequency normalized impedance to examine if the dispersion relations are satisfied for a given impedance tensor. A version of the Shannon sampling theory is generalized for the unequally sampled data. The method involves the reconstruction of the measured data by a linear combination of an analytic interpolation function distributed along the horizontal axis. Then, the decomposition coefficients that provide a fit between the measured and reconstructed data are solved using the linear least-squares method with singular-value decomposition. Finally, the discrete Hilbert transformed data are constructed at any desired abscissa values by the sum of the analytic Hilbert transform of the interpolation function using the decomposition coefficients solved in the previous step. Examples from the MT synthetic and field data, including out-of-quadrant phase cases, are given. In principle, the method also can be applied to other integral transforms.
Architecture characteristics of hyperpycnal deposits: Insights from numerical modeling with numerical simulation platform grade
Authors: Wang Yang-Jun , Yin Taiju , Tang Yong , Zou Yang , Wenjun He , Liliang Huang , Cheng Zhao , Li Zhuo-Yi
Published: November 2022

It is challenging to study hyperpycnal flow deposit characteristics, distribution, and internal architecture in detail using seismic or flume experiments. Therefore, a rule-based model numerical simulation platform (NSP) grade has been developed to simulate various gravity-driven sediment transport processes and fan depositions in three dimensions. Five model scenarios are designed for processing and architecture studies of hyperpycnal flow deposits. Furthermore, the impact of a single flow event’s duration and the flow occurrence also are discussed. The results find that, in all scenarios, complex hyperpycnal flow strata stacked by channels, fans, and background shale according to specific rules were generated, and the progradation, retrogradation, and compensational stacking of hyperpycnal flow sediments were observed. Three facies can be identified in hyperpycnal flow depositions from proximal to the distal deposits, comprising channel complex, channel-fan transition deposits, and fan complex. Due to hyperpycnal deposit development, each event’s channel gradually becomes increasingly complex, and the channel extension distance decreases. The retrogradation characteristics of sedimentary bodies become more apparent. Shortening a flood event’s duration will lead to stronger deposition heterogeneity. Here, multiple depositional centers will be formed. The distal center will form first, and sediments will gradually retrograde to form the next one. The reduced frequency of events results in less sediment supply, thinner thickness, and thicker mudstone barriers. NSP grade reveals that numerical simulation could provide more realistic results than traditional interpretation models. Further studies on NSP grade modeling will couple more processes and improve model accuracy to guide the understanding of hyperpycnal flow depositions.
Epilepsy, intellectual disability and the epilepsy care pathway: improving outcomes
Authors: Kerr Michael , Goodwin Geraldine , Hanna Jane
Published: November 2022

The strong, life-long association between epilepsy and intellectual disability means that psychiatric teams, and the services they exist in, have a need for significant competencies in the field of epilepsy. This article addresses these competencies through the pathway of care. It will focus on those areas most relevant to psychiatric care and, when possible, explore where technology has begun to influence practice. The pathway leads from diagnosis through, in some cases, to mortality and support of the bereaved in psychiatric care. We will approach the topic through showing how the intertwining themes of information, empowerment, access to care, assessment of risk and psychological support are important. Technological advances are supporting changes in most of these areas, and psychological support, a knowledge of the needs of people with epilepsy and intellectual disability and epilepsy skills remain the foundation in the application of these advances.