bluuebunny/crossref_metadata_2025 huggingface dataset:
A foliar pigment-based bioassay for interrogating chloroplast signalling revealed that carotenoid isomerisation regulates chlorophyll abundance
Authors: Dhami N. , Pogson B. J. , Tissue D. T. , Cazzonelli C. I.
Published: February 2022

Background

Some plastid-derived metabolites can control nuclear gene expression, chloroplast biogenesis, and chlorophyll biosynthesis. For example, norflurazon (NFZ) induced inhibition of carotenoid biosynthesis in leaves elicits a protoporphyrin IX (Mg-ProtoIX) retrograde signal that controls chlorophyll biosynthesis and chloroplast development. Carotenoid cleavage products, known as apocarotenoids, also regulate plastid development. The key steps in carotenoid biosynthesis or catabolism that can regulate chlorophyll biosynthesis in leaf tissues remain unclear. Here, we established a foliar pigment-based bioassay using Arabidopsis rosette leaves to investigate plastid signalling processes in young expanding leaves comprising rapidly dividing and expanding cells containing active chloroplast biogenesis.

Results

We demonstrate that environmental treatments (extended darkness and cold exposure) as well as chemical (norflurazon; NFZ) inhibition of carotenoid biosynthesis, reduce chlorophyll levels in young, but not older leaves of Arabidopsis. Mutants with disrupted xanthophyll accumulation, apocarotenoid phytohormone biosynthesis (abscisic acid and strigolactone), or enzymatic carotenoid cleavage, did not alter chlorophyll levels in young or old leaves. However, perturbations in acyclic cis-carotene biosynthesis revealed that disruption of CAROTENOID ISOMERASE (CRTISO), but not ZETA-CAROTENE ISOMERASE (Z-ISO) activity, reduced chlorophyll levels in young leaves of Arabidopsis plants. NFZ-induced inhibition of PHYTOENE DESATURASE (PDS) activity caused higher phytoene accumulation in younger crtiso leaves compared to WT indicating a continued substrate supply from the methylerythritol 4-phosphate (MEP) pathway.

Conclusion

The Arabidopsis foliar pigment-based bioassay can be used to differentiate signalling events elicited by environmental change, chemical treatment, and/or genetic perturbation, and determine how they control chloroplast biogenesis and chlorophyll biosynthesis. Genetic perturbations that impaired xanthophyll biosynthesis and/or carotenoid catabolism did not affect chlorophyll biosynthesis. The lack of CAROTENOID ISOMERISATION reduced chlorophyll accumulation, but not phytoene biosynthesis in young leaves of Arabidopsis plants growing under a long photoperiod. Findings generated using the newly customised foliar pigment-based bioassay implicate that carotenoid isomerase activity and NFZ-induced inhibition of PDS activity elicit different signalling pathways to control chlorophyll homeostasis in young leaves of Arabidopsis.
Distinct patterns of emotional and behavioral change in child psychiatry outpatients during the COVID-19 pandemic
Authors: Doyle Alysa E. , Colvin Mary K. , Beery Clara S. , Koven Maya R. , Vuijk Pieter J. , Braaten Ellen B.
Published: February 2022

Background

Studies are documenting the impact of the COVID-19 pandemic on youth mental health. We extended this literature by characterizing a child psychiatric outpatient sample in the United States during the middle of the 2020–2021 school year. We also used a computational strategy to identify distinct patterns of psychopathology symptom change and examined correlates and predictors of such change. Among potential predictors were cognition and clinical diagnoses, which have not been studied in this context previously.

Methods

Participants were 171 youth (aged 10.6 ± 3.1) referred for neuropsychiatric evaluation who enrolled in research and whose parents filled out a survey on COVID-19. The questionnaire included eight psychiatric and six psychosocial domains rated retrospectively prior to the pandemic and currently at the time of evaluation. We examined change in severity of individual domains with Wilcoxon signed-rank tests. We used a latent profile analysis (LPA) to identify groups with distinct symptom change profiles. Using multinomial logistic regression, we examined potential predictors and correlates of LPA-derived groups. Models controlled for age, sex, and assessment date and corrected for multiple testing.

Results

Although the majority of individual psychopathology domains were worse on average during the 2020–2021 school year, youth showed distincive patterns of symptom change. In addition to a large group (72.2%) with relatively stable symptoms and a small group (6.4%) that improved on most symptoms, there were two groups with different constellations of worsening symptoms. These latter groups both showed increased sadness, anxiety and oppositionality; however, one had increased hyperactivity/impulsivity and no change in hopelessness while the other showed greater hopelessness and no change in hyperactivity. Symptoms related to the distinguishable domains of these groups predicted group membership, and changes in screen time, conflict with parents and social isolation were correlates of worsening. Cognition and lifetime clinical diagnoses failed to predict group membership.

Conclusions

In youth outpatients, psychiatric and psychosocial difficulties were worse on average during the school year following the spring 2020 COVID-19 lockdown; yet, some youth experienced greater and distinctive symptom change. A personalized approach to support may be needed as youth emerge from this period.
Sleep and mental health in childhood: a multi-method study in the general pediatric population
Authors: Blok Elisabet , Koopman-Verhoeff M. Elisabeth , Dickstein Daniel P. , Saletin Jared , Luik Annemarie I. , Rijlaarsdam Jolien , Hillegers Manon , Kocevska Desana , White Tonya , Tiemeier Henning
Published: February 2022

Background

Sleep problems, altered sleep patterns and mental health difficulties often co-occur in the pediatric population. Different assessment methods for sleep exist, however, many studies only use one measure of sleep or focus on one specific mental health problem. In this population-based study, we assessed different aspects of sleep and mother-reported mental health to provide a broad overview of the associations between reported and actigraphic sleep characteristics and mental health.

Methods

This cross-sectional study included 788 children 10-11-year-old children (52.5% girls) and 344 13–14-year-old children (55.2% girls). Mothers and children reported on the sleep of the child and wrist actigraphy was used to assess the child’s sleep patterns and 24 h activity rhythm. Mental health was assessed via mother-report and covered internalizing, externalizing and a combined phenotype of internalizing and externalizing symptoms, the dysregulation profile.

Results

Higher reported sleep problems were related to more symptoms of mental health problems in 10–11- and 13–14-year-old adolescents, with standardized ß-estimates ranging between 0.11 and 0.35. There was no association between actigraphy-estimated sleep and most mental health problems, but earlier sleep onset was associated with more internalizing problems (ß = − 0.09, SE = 0.03, p-value = 0.002), and higher intra-daily variability of the 24 h activity rhythm was associated with more dysregulation profile symptoms at age 10–11 (ß = 0.11, SE = 0.04, p-value = 0.002).

Discussion

Reported sleep problems across informants were related to all domains of mental health problems, providing evidence that sleep can be an important topic to discuss for clinicians seeing children with mental health problems. Actigraphy-estimated sleep characteristics were not associated with most mental health problems. The discrepancy between reported and actigraphic sleep measures strengthens the idea that these two measures tap into distinct constructs of sleep.
Uniparental disomy is a chromosomic disorder in the first place
Authors: Liehr Thomas
Published: February 2022

Background

Uniparental disomy (UPD) is well-known to be closely intermingled with imprinting disorders. Besides, UPD can lead to a disease by ‘activation’ of a recessive gene mutation or due to incomplete (cryptic) trisomic rescue. Corresponding to all common theories how UPD forms, it takes place as a consequence of a “chromosomic problem”, like an aneuploidy or a chromosomal rearrangement. Nonetheless, UPD is rarely considered as a cytogenetic, but most often as a molecular genetic problem.

Results

Here a review on the ~ 4900 published UPD-cases is provided, and even though being biased as discussed in the paper, the following insights have been given from that analysis: (1) the rate of maternal to paternal UPD is 2~3 to 1; (2) at most only ~ 0.03% of the available UPD cases are grasped scientifically, yet; (3) frequencies of single whole-chromosome UPDs are non-random, with UPD(16) and UPD(15) being most frequent in clinically healthy and diseased people, respectively; (4) there is a direct correlation of UPD frequency and known frequent first trimester trisomies, except for chromosomes 1, 5, 11 and 18 (which can be explained); (5) heterodisomy is under- and UPD-mosaicism is over-represented in recent reports; and (6) cytogenetics is not considered enough when a UPD is identified.

Conclusions

As UPD is diagnosed using molecular genetic approaches, and thus by specialists considering chromosomes at best as a whim of nature, most UPD reports lack the chromosomal aspect. Here it is affirmed and substantiated by corresponding data that UPD is a chromosomic disorder in the first place and cytogenetic analyses is indicated in each diagnosed UPD-case.
RelB upregulates PD-L1 and exacerbates prostate cancer immune evasion
Authors: Zhang Yanyan , Zhu Shuyi , Du Yuanyuan , Xu Fan , Sun Wenbo , Xu Zhi , Wang Xiumei , Qian Peipei , Zhang Qin , Feng Jifeng , Xu Yong
Published: February 2022

Background

The interaction between programmed death receptor (PD-1) and its ligand (PD-L1) is essential for suppressing activated T-lymphocytes. However, the precise mechanisms underlying PD-L1 overexpression in tumours have yet to be fully elucidated. Here, we describe that RelB participates in the immune evasion of prostate cancer (PCa) via cis/trans transcriptional upregulation of PD-L1.

Methods

Based on transcriptome results, RelB was manipulated in multiple human and murine PCa cell lines. Activated CD4+ and CD8+ T cells were cocultured with PCa cells with different levels of RelB to examine the effect of tumourous RelB on T cell immunity. Male mice were injected with murine PCa cells to validate the effect of RelB on the PD-1/PD-L1-mediated immune checkpoint using both tumour growth and metastatic experimental models.

Results

PD-L1 is uniquely expressed at a high level in PCa with high constitutive RelB and correlates with the patients’ Gleason scores. Indeed, a high level of PD-L1 is associated with RelB nuclear translocation in AR-negative aggressive PCa cells. Conversely, the silencing of RelB in advanced PCa cells resulted in reduced PD-L1 expression and enhanced susceptibility of PCa cells to the T cell immune response in vitro and in vivo. Mechanistically, a proximal NF-κB enhancer element was identified in the core promoter region of the human CD274 gene, which is responsible for RelB-mediated PD-L1 transcriptional activation. This finding provides an informative insight into immune checkpoint blockade by administering RelB within the tumour microenvironment.

Conclusion

This study deciphers the molecular mechanism by which tumourous RelB contributes to immune evasion by inhibiting T cell immunity via the amplification of the PD-L1/PD-1-mediated immune checkpoint.
Alternating Hemiplegia of Childhood: neurological comorbidities and intrafamilial variability
Authors: Pavone Piero , Pappalardo Xena Giada , Mustafa Naira , Cho Sung Yoon , Jin Dong Kyu , Incorpora Gemma , Falsaperla Raffaele , Marino Simona Domenica , Corsello Giovanni , Parano Enrico , Ruggieri Martino
Published: February 2022

Background

Alternating of Childhood (AHC) is an uncommon and complex disorder characterized by age of onset before 18 months with recurrent hemiplegia of one or either sides of the body or quadriplegia. The disorder is mainly caused by mutations in ATP1A3 gene, and to a lesser extent in ATP1A2 gene. In AHC neurological co-morbidities are various and frequently reported including developmental delay, epilepsy, tonic or dystonic spells, nystagmus,autonomic manifestations with intrafamilial variability.

Case presentation

Clinical and genetic findings of a couple of twins (Family 1: Case 1 and Case 2) and a couple of siblings (Family 2: Case 3 and Case 4) coming from two different Italian families affected by AHC were deeply examined. In twins of Family 1, a pathogenic variant in ATP1A3 gene (c.2318A>G) was detected. In siblings of Family 2, the younger brother showed a novel GRIN2A variant (c.3175 T > A), while the older carried the same GRIN2A variant, and two missense mutations in SCNIB (c.632 > A) and KCNQ2 (1870 G > A) genes. Clinical manifestations of the four affected children were reported along with cases of AHC drawn from the literature.

Conclusions

Hemiplegic episode is only a sign even if the most remarkable of several and various neurological comorbidities in AHC affected individuals. Molecular analysis of the families here reported showed that clinical features of AHC may be also the result of an unexpected genetic heterogeneity.
Should obesogenic- effect be replaced with adipose tissue related alterations in childhood?
Authors: Mohn Angelika Anna , Polidori Nella
Published: February 2022

During the last year, primary prevention programs for childhood obesity have not obtained the goal in decreasing the prevalence of obesity in pediatric population. This phenomenon remains a crucial issue for the future translating itself in major health problems for the next young-adult generation. However ectopic adipose tissue distribution shows the same obesogenic effect also in slim people. Therefore, the use of adequate language is essential to develop consciousness of overall healthy lifestyle throughout the population. We therefore propone to replace “obesogenic effect” with adipose tissue related alterations also in childhood population.
The influence of culture-dependent native microbiota in Zika virus infection in Aedes aegypti
Authors: do Nascimento Rêgila Mello , Campolina Thais Bonifácio , Chaves Barbara Aparecida , Delgado Jessica Lana Fernandes , Godoy Raquel Soares Maia , Pimenta Paulo Filemon Paolucci , Secundino Nagila Francinete Costa
Published: February 2022

Background

Emerging and re-emerging vector-borne diseases (VBDs) pose a recurring threat to tropical countries, mainly due to the abundance and distribution of theAedes aegyptimosquito, which is a vector of the Zika, dengue, chikungunya, and yellow fever arboviruses.

Methods

Female 3–5 day-oldAe. aegyptiwere distributed into two experimental groups: group I—survey of cultivable bacteria; sucrose group: fed only on sucrose, i.e., non-blood-fed (UF); blood-fed group: (i) fed with non-infected blood (BF); (ii) fed with blood infected with the Zika virus (BZIKV); (iii) pretreated with penicillin/streptomycin (pen/strep), and fed with non-infected blood (TBF); (iv) pretreated with pen/strep and fed blood infected with ZIKV, i.e., gravid with developed ovaries, (TGZIKV); group II—experimental co-infections: bacteria genera isolated from the group fed on sucrose, i.e., non-blood-fed (UF).

Results

Using the cultivable method and the same mosquito colony and ZIKV strain described by in a previous work, our results reveled 11 isolates (Acinetobacter,Aeromonas,Cedecea,Cellulosimicrobium,Elizabethkingia,Enterobacter,Lysinibacillus,Pantoea,Pseudomonas,Serratia, andStaphylococcus).Enterobacterwas present in all evaluated groups (i.e., UF, BF, BZIKV, TBF, and TGZIKV), whereasElizabethkingiawas present in the UF, BZIKV, and TBF groups.Pseudomonaswas present in the BZIKV and TBF groups, whereasStaphylococcuswas present in the TBF and TGZIKV groups. The only genera of bacteria that were found to be present in only one group wereAeromonas,Lysinibacillus, andSerratia(UF);Cedacea,PantoeaandAcinetobacter(BF); andCellulosimicrobium(BZIKV). The mosquitoes co-infected with ZIKV plus the isolates group fed on sucrose (UF) showed interference in the outcome of infection.

Conclusions

We demonstrate that the distinct feeding aspects assessed herein influence the composition of bacterial diversity. In the co-infection, among ZIKV,Ae. aegyptiand the bacterial isolates, the ZIKV/Lysinibacillus–Ae. aegyptihad the lowest number of viral copies in the head-SG, which means that it negatively affects vector competence. However, when the saliva was analyzed after forced feeding, no virus was detected in the mosquito groups ZIKV/Lysinibacillus–Lu. longipalpisandAe. aegypti; the combination of ZIKV/Serratiamay interfere in salivation. This indicates that the combinations do not produce viable viruses and may have great potential as a method of biological control.

Graphical Abstract
Integrating single-cell sequencing data with GWAS summary statistics reveals CD16+monocytes and memory CD8+T cells involved in severe COVID-19
Authors: Ma Yunlong , Qiu Fei , Deng Chunyu , Li Jingjing , Huang Yukuan , Wu Zeyi , Zhou Yijun , Zhang Yaru , Xiong Yichun , Yao Yinghao , Zhong Yigang , Qu Jia , Su Jianzhong
Published: February 2022

Background

Understanding the host genetic architecture and viral immunity contributes to the development of effective vaccines and therapeutics for controlling the COVID-19 pandemic. Alterations of immune responses in peripheral blood mononuclear cells play a crucial role in the detrimental progression of COVID-19. However, the effects of host genetic factors on immune responses for severe COVID-19 remain largely unknown.

Methods

We constructed a computational framework to characterize the host genetics that influence immune cell subpopulations for severe COVID-19 by integrating GWAS summary statistics (N= 969,689 samples) with four independent scRNA-seq datasets containing healthy controls and patients with mild, moderate, and severe symptom (N= 606,534 cells). We collected 10 predefined gene sets including inflammatory and cytokine genes to calculate cell state score for evaluating the immunological features of individual immune cells.

Results

We found that 34 risk genes were significantly associated with severe COVID-19, and the number of highly expressed genes increased with the severity of COVID-19. Three cell subtypes that are CD16+monocytes, megakaryocytes, and memory CD8+T cells were significantly enriched by COVID-19-related genetic association signals. Notably, three causal risk genes ofCCR1,CXCR6, andABOwere highly expressed in these three cell types, respectively.CCR1+CD16+monocytes andABO+megakaryocytes with significantly up-regulated genes, includingS100A12,S100A8,S100A9, andIFITM1, confer higher risk to the dysregulated immune response among severe patients.CXCR6+memory CD8+ T cells exhibit a notable polyfunctionality including elevation of proliferation, migration, and chemotaxis. Moreover, we observed an increase in cell-cell interactions of bothCCR1+CD16+monocytes andCXCR6+memory CD8+T cells in severe patients compared to normal controls among both PBMCs and lung tissues. The enhanced interactions ofCXCR6+memory CD8+T cells with epithelial cells facilitate the recruitment of this specific population of T cells to airways, promoting CD8+T cell-mediated immunity against COVID-19 infection.

Conclusions

We uncover a major genetics-modulated immunological shift between mild and severe infection, including an elevated expression of genetics-risk genes, increase in inflammatory cytokines, and of functional immune cell subsets aggravating disease severity, which provides novel insights into parsing the host genetic determinants that influence peripheral immune cells in severe COVID-19.
A multi-step approach to managing missing data in time and patient variant electronic health records
Authors: Cesare Nina , Were Lawrence P. O.
Published: February 2022

Objective

Electronic health records (EHR) hold promise for conducting large-scale analyses linking individual characteristics to health outcomes. However, these data often contain a large number of missing values at both the patient and visit level due to variation in data collection across facilities, providers, and clinical need. This study proposes a stepwise framework for imputing missing values within a visit-level EHR dataset that combines informative missingness and conditional imputation in a scalable manner that may be parallelized for efficiency.

Results

For this study we use a subset of data from AMPATH representing information from 530,812 clinic visits from 16,316 Human Immunodeficiency Virus (HIV) positive women across Western Kenya who have given birth. We apply this process to a set of 84 clinical, social and economic variables and are able to impute values for 84.6% of variables with missing data with an average reduction in missing data of approximately 35.6%. We validate the use of this imputed dataset by predicting National Hospital Insurance Fund (NHIF) enrollment with 94.8% accuracy.
Correction of carotid artery stenosis by stent placement ameliorated paroxysmal hypertension after radiation treatment of hypopharyngeal carcinoma: a case report
Authors: Brook Itzhak , Cohen Ezra , Stemer Andrew
Published: February 2022

Background

Paroxysmal hypertension can be associated with failure of the carotid artery baroreceptors due to past exposure to radiation treatment. This report describes a patient whose repeated paroxysmal hypertensive episodes were ameliorated following placement of a carotid artery stent for the treatment of carotid artery stenosis.

Case report

A 79-year-old caucasian male was diagnosed with hypopharyngeal squamous cell carcinoma (T1, L0, M0) in 2006, and received 70 Gy intensity-modulated radiotherapy in 2006 and underwent a total laryngectomy in 2008. He experienced paroxysmal hypertensive episodes since 2010 that exacerbated in frequency in 2019. Eighty percent left internal carotid artery stenosis was demonstrated by ultrasound and arteriography. Angioplasty and stenting of the left carotid artery was performed. A Doppler ultrasound study performed 5 months after the stent placement did not reveal any hemodynamic stenosis in the left carotid artery. The patient experienced postprandial hypotension and had experienced only three episodes of paroxysmal hypertension in the following 24 months. He was able to abort paroxysmal hypertensive episodes by eating warm food.

Discussion

This is the first report of a patient whose paroxysmal hypertensive episodes that occurred following radiation of the neck subsided after placement of a stent in a stenotic carotid artery. The exact mechanism leading to this phenomena is unknown but may be due to several factors. The reversal of the carotid artery stent and improvement in blood flow to the carotid artery baroceptors may play a role in this phenomenon.

Conclusion

The ability to ameliorate paroxysmal hypertensive episodes in a patient with carotid artery stenosis by stent placement may be a promising therapeutic intervention for paroxysmal hypertension.
Is it time to reconsider the administration of thiamine alone or in combination with vitamin C in critically ill patients? A meta-analysis of clinical trial studies
Authors: Shokri-mashhadi Nafiseh , Aliyari Ali , Hajhashemy Zahra , Saadat Saeed , Rouhani Mohammad Hossein
Published: February 2022

Background

Although the effect of thiamine alone or in combination with vitamin C has been studied in multiple trials (RCT and interventional studies), their results are inconsistent. This meta-analysis aimed to assess impact of thiamine administration alone, thiamine in combination with vitamin C, and co-administration of low-dose hydrocortisone, vitamin C and thiamine (HVT) on clinical outcomes in critically ill patients.

Methods and materials

After electronic searches on PubMed, Scopus, Cochrane Library, and Web of Science databases, initially 3367 papers were found, and 20 interventional studies were included in our analysis. We assessed the risk-difference between treatment and control (standard treatment) groups by pooling available data on ICU length of stay, number of ventilator free days, mortality, and changes in Sequential Organ Failure Assessment (SOFA) scores.

Results

The results of present studies revealed no significant effect of thiamine in combination with vitamin C, and HVT on number of free days of ventilation. Thiamine alone supplementation was associated with high mortality percentage (WMD: 5.17%; 95% CI: 2.67, 7.67). Thiamine in combination with vitamin C had no significant impact on mortality rate. In contrast, HVT could decrease mortality rate (WMD: − 7.23%; 95% CI: − 10.31, − 4.16; I-square: 0.0%). There was no significant effect of thiamine alone, co-administration of thiamine and vitamin C, and HVT on ICU length of stay. The results of the meta-analysis showed that thiamine alone and HVT supplementation had no significant effect on SOFA score. Interestingly, co-supplementation of thiamine and vitamin C had a significant decreasing effect on SOFA score (WMD: − 0.73; 95% CI: − 1.29, − 0.17; I-square: 0.0%).

Conclusion

In contrast to HVT, thiamine supplementation alone was associated with increased mortality rate in ICU. However, co-supplementation of thiamine and vitamin C had a significant decreasing effect on SOFA score.
In silico analyses of maleidride biosynthetic gene clusters
Authors: Williams Katherine , de Mattos-Shipley Kate M. J. , Willis Christine L. , Bailey Andrew M.
Published: February 2022

Maleidrides are a family of structurally related fungal natural products, many of which possess diverse, potent bioactivities. Previous identification of several maleidride biosynthetic gene clusters, and subsequent experimental work, has determined the ‘core’ set of genes required to construct the characteristic medium-sized alicyclic ring with maleic anhydride moieties. Through genome mining, this work has used these core genes to discover ten entirely novel putative maleidride biosynthetic gene clusters, amongst both publicly available genomes, and encoded within the genome of the previously un-sequenced epiheveadride producer Wicklowia aquatica CBS 125634. We have undertaken phylogenetic analyses and comparative bioinformatics on all known and putative maleidride biosynthetic gene clusters to gain further insights regarding these unique biosynthetic pathways.
Concurrent wasting and stunting among children 6–59 months: an analysis using district-level survey data in Mozambique
Authors: Zaba Tomás , Conkle Joel , Nyawo Mara , Foote Dorothy , Myatt Mark
Published: February 2022

Background

In the past it was believed that wasting and stunting were independent of each other. Recent work has shown that they can occur concurrently in a child and that increases considerably the risk of mortality. Concurrent wasting and stunting (WaSt) is currently defined as WHZ < -2 AND HAZ < -2. Wasting is measured by WHZ and MUAC and evidence shows that they tend to identify different sets of children. Our study aimed to look at the effect of adding MUAC on the prevalence and burden of WaSt, and to assess diagnosis of WaSt with a single measurement.

Methods

We analyzed population-based anthropometric surveys from 37 districts in Mozambique conducted by the Government of Mozambique between 2017 and 2019. We proposed a new case-definition for WaSt that includes MUAC in acknowledgement of the different children with wasting diagnosed by WHZ and MUAC. We estimated how many WaSt cases are eligible to be included in the existing treatment program in Mozambique by calculating the True Positive and False Positive Values of WaSt using our proposed case-definition against the wasting admission criteria. AUC of ROC curves used for MUAC and WAZ and optimal cut-offs were determined using Youden’s Index.

Results

Including MUAC in the concurrent WaSt case-definition identified more children with WaSt compared to the original case-definition and more younger children and girls were identified. Using both MUAC and WHZ and enrolling severe and moderate wasting is already picking up most of the WaSt cases: 100% in health facilities and 79.40% with MUAC mass screenings at community level. Cut-off values from the ROC curve for the proposed case-definition were MUAC ≤133 mm and WAZ ≤ 2.145 Z-scores, however, they  yielded many false positive values.

Conclusion

WaSt case-definition should include MUAC. WaSt should commence to be reported in surveys and Mozambique should also start monitoring and treating children with WaSt. A cost-effective approach to identify all children with WaSt without adding too many false positive is needed, as well as understanding how to achieve optimal treatment outcomes within existing programs.
Concerns regarding the validity of nutrition self-efficacy questionnaire among Iranian elderly population
Authors: Pahlevan Sharif Saeed , Naghavi Navaz , Sharif Nia Hamid
Published: February 2022

There are some statistical concerns regarding a recently published article which has claimed to develop and psychometrically evaluate an instrument to assess the nutrition self-efficacy among Iranian elderly population.
The effect of low-frequency repetitive transcranial magnetic stimulation on left dorsolateral prefrontal cortex in patients with the obsessive-compulsive disorder: a double-blinded, sham-controlled clinical trial
Authors: Diarjani Adeleh Askari , Javadi Seyed Alireza Haji Seyed
Published: February 2022

Background

Obsessive-compulsive disorder (OCD) is a complicated neuropsychiatric disorder, which its prevalence ranges from 2 to 4%. In 30–60% of patients due to intolerance of side effects or partial response to treat symptoms of the disease remain or relapse. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive therapeutic option to treat this condition. Transcranial magnetic stimulation can be applied for treating with no anesthesia. The current study intended to evaluate the effectiveness of low-frequency rTMS on the left dorsolateral prefrontal cortex as an adjunct treatment in combination with standard medication in patients with OCD.

Results

In both groups of intervention and sham, the Y-BOCS scale was decreased. There was no significant difference between the two groups (P=0.82). Also after 15 sessions, the symptoms of OCD patients were improved. Although the treatment process was the same in the control group, none of the patients showed any serious complications, such as seizures, severe headache, neurological complication, or cognitive impairment during treatment.

Conclusions

It seems that treatment with 1 Hz rTMS on the left dorsolateral prefrontal cortex does not play an effective role in the recovery of OCD patients.

Trial registration

Name of the registry: Therapeutic effect comparison of the Repetitive Transcranial MagneticMagnetic Stimulation (RTMS) combination therapy with drug versus medication monotherapy in obsessive-compulsive disorder (OCD). Trial registration number: IRCT ID: IRCT20200728048240N1. Date of registration: 2020/8/8.
A variational approach for picking optimal surfaces from semblance-like panels
Authors: Decker Luke , Fomel Sergey
Published: February 2022

We propose and examine a variational method for determining optimal velocity fields from semblance-like volumes using continuation. The proposed approach finds a minimal-cost surface through a volume, which often corresponds to a velocity field within a semblance scan. This allows picked velocity fields to incorporate information from gathers that are spatially near the midpoint in question. The minimization process amounts to solving a nonlinear elliptic partial differential equation, which is accomplished by changing the elliptic problem to a parabolic one and solving it iteratively until it converges to a critical point which minimizes the cost functional. The continuation approach operates by using a variational framework to iteratively minimize the cost of a velocity surface through successively less-smoothed semblance scans. The method works because a global minimum for the velocity cost functional can only exist when the semblance scan varies smoothly in space and convexly in the parameter being scanned. Using a discretization of the functional with a limited-memory Broyden-Fletcher-Goldfarb-Shanno algorithm, we illustrate how the continuation approach is able to avoid local minima that would typically capture the iterative solution of an optimal velocity field determined without continuation by applying the method to seismic processing of a field data set from the Viking Graben. We then use a field data set from the Gulf of Mexico to show how the final velocity model determined by the method using continuation is largely independent of the starting velocity model, producing something resembling a global minimum. Finally, we demonstrate the versatility of the variational picking approach by using it to automatically interpret a seismic horizon from the Heidrun Field.
Predicting patients who will drop out of out-patient psychotherapy using machine learning algorithms
Authors: Bennemann Björn , Schwartz Brian , Giesemann Julia , Lutz Wolfgang
Published: February 2022

Background

About 30% of patients drop out of cognitive–behavioural therapy (CBT), which has implications for psychiatric and psychological treatment. Findings concerning drop out remain heterogeneous.

Aims

This paper aims to compare different machine-learning algorithms using nested cross-validation, evaluate their benefit in naturalistic settings, and identify the best model as well as the most important variables.

Method

The data-set consisted of 2543 out-patients treated with CBT. Assessment took place before session one. Twenty-one algorithms and ensembles were compared. Two parameters (Brier score, area under the curve (AUC)) were used for evaluation.

Results

The best model was an ensemble that used Random Forest and nearest-neighbour modelling. During the training process, it was significantly better than generalised linear modelling (GLM) (Brier score: d = –2.93, 95% CI (−3.95, −1.90)); AUC: d = 0.59, 95% CI (0.11 to 1.06)). In the holdout sample, the ensemble was able to correctly identify 63.4% of cases of patients, whereas the GLM only identified 46.2% correctly. The most important predictors were lower education, lower scores on the Personality Style and Disorder Inventory (PSSI) compulsive scale, younger age, higher scores on the PSSI negativistic and PSSI antisocial scale as well as on the Brief Symptom Inventory (BSI) additional scale (mean of the four additional items) and BSI overall scale.

Conclusions

Machine learning improves drop-out predictions. However, not all algorithms are suited to naturalistic data-sets and binary events. Tree-based and boosted algorithms including a variable selection process seem well-suited, whereas more advanced algorithms such as neural networks do not.
Intermittent ERK oscillations downstream of FGF in mouse embryonic stem cells
Authors: Raina Dhruv , Fabris Fiorella , Morelli Luis G. , Schröter Christian
Published: February 2022

Signal transduction networks generate characteristic dynamic activities to process extracellular signals and guide cell fate decisions such as to divide or differentiate. The differentiation of pluripotent cells is controlled by FGF/ERK signaling. However, only a few studies have addressed the dynamic activity of the FGF/ERK signaling network in pluripotent cells at high time resolution. Here, we use live cell sensors in wild-type and Fgf4-mutant mouse embryonic stem cells to measure dynamic ERK activity in single cells, for defined ligand concentrations and differentiation states. These sensors reveal pulses of ERK activity. Pulsing patterns are heterogeneous between individual cells. Consecutive pulse sequences occur more frequently than expected from simple stochastic models. Sequences become more prevalent with higher ligand concentration, but are rarer in more differentiated cells. Our results suggest that FGF/ERK signaling operates in the vicinity of a transition point between oscillatory and non-oscillatory dynamics in embryonic stem cells. The resulting heterogeneous dynamic signaling activities add a new dimension to cellular heterogeneity that may be linked to divergent fate decisions in stem cell cultures.
The RASopathies: from pathogenetics to therapeutics
Authors: Hebron Katie E. , Hernandez Edjay Ralph , Yohe Marielle E.
Published: February 2022

The RASopathies are a group of disorders caused by a germline mutation in one of the genes encoding a component of the RAS/MAPK pathway. These disorders, including neurofibromatosis type 1, Noonan syndrome, cardiofaciocutaneous syndrome, Costello syndrome and Legius syndrome, among others, have overlapping clinical features due to RAS/MAPK dysfunction. Although several of the RASopathies are very rare, collectively, these disorders are relatively common. In this Review, we discuss the pathogenesis of the RASopathy-associated genetic variants and the knowledge gained about RAS/MAPK signaling that resulted from studying RASopathies. We also describe the cell and animal models of the RASopathies and explore emerging RASopathy genes. Preclinical and clinical experiences with targeted agents as therapeutics for RASopathies are also discussed. Finally, we review how the recently developed drugs targeting RAS/MAPK-driven malignancies, such as inhibitors of RAS activation, direct RAS inhibitors and RAS/MAPK pathway inhibitors, might be leveraged for patients with RASopathies.
Cardiorespiratory Fitness, BMI, Mortality, and Cardiovascular Disease in Adults with Overweight/Obesity and Type 2 Diabetes
Authors: WILLS ANDREW C. , VAZQUEZ ARREOLA ELSA , OLAIYA MUIDEEN T. , CURTIS JEFFREY M. , HELLGREN MARGARETA I. , HANSON ROBERT L. , KNOWLER WILLIAM C.
Published: February 2022

Introduction

We estimated the effects of cardiorespiratory fitness (CRF) and body mass index (BMI) at baseline on mortality and cardiovascular disease events in people with type 2 diabetes who participated in the Look AHEAD randomized clinical trial.

Methods

Look AHEAD compared effects of an intensive lifestyle intervention with diabetes support and education on cardiovascular disease events in 5145 adults age 45–76 yr with overweight/obesity and type 2 diabetes. In 4773 participants, we performed a secondary analysis of the association of baseline CRF during maximal treadmill test (expressed as metabolic equivalents (METs)) on mortality and cardiovascular disease events during a mean follow-up of 9.2 yr.

Results

The mean (SD) CRF was 7.2 (2.0) METs. Adjusted for age, sex, race/ethnicity, BMI, intervention group, and β-blocker use, all-cause mortality rate was 30% lower per SD greater METs (hazard ratio (HR) = 0.70 (95% confidence interval, 0.60 to 0.81); rate difference (RD), −2.71 deaths/1000 person-years (95% confidence interval, −3.79 to −1.63)). Similarly, an SD greater METs predicted lower cardiovascular disease mortality (HR, 0.45; RD, −1.65 cases/1000 person-years) and a composite cardiovascular outcome (HR, 0.72; RD, −6.38). Effects of METs were homogeneous on the HR scale for most baseline variables and outcomes but heterogeneous for many on the RD scale, with greater RD in subgroups at greater risk of the outcomes. For example, all-cause mortality was lower by 7.6 deaths/1000 person-years per SD greater METs in those with a history of cardiovascular disease at baseline but lower by only 1.6 in those without such history. BMI adjusted for CRF had little or no effect on these outcomes.

Conclusions

Greater CRF is associated with reduced risks of mortality and cardiovascular disease events.
Cohort study on educational well-being of children of Chinese origin adopted into transracial and international families in the Spanish education system
Authors: Doncel-Abad David , Cabrera-Álvarez Pablo
Published: February 2022

The following dataset focuses on the educational well-being of adopted girls of Chinese origin in Spanish schools. Due to its characteristics, the presence of this group may generate complex interaction dynamics in school; particularly regarding bullying in school linked to factors such as the acceptance of others. These are dynamics, which may indeed condition the educational experience of this social group. Therefore, the aim of creating this dataset is to measure the educational well-being of children of Chinese origin adopted into transracial families in Spain. Although this research was justified by the lack of studies on this social group, we aimed to go one-step further, we also studied the correlation between this social group’s educational experience, and to what extent they show an interest in Chinese culture. As we have written before, we incorporated the concept of Well-Being and we worked with the following indicators: Satisfaction with Life, Social Life, and Bullying in School, Racial Bullying, Personal Identity and Interest in Chinese Culture. To achieve the objective set forth, we conducted a questionnaire. The final sample consisted of 268 individuals. The creation of this dataset provided us with information that can shed light on the relationship between adoption, race/ethnicity and the educational experience of adopted children of Chinese origin.
Semiotics of the pornographic face: From traditional porno to Beautiful Agony
Authors: Surace Bruno
Published: February 2022

Today’s pornography constitutes a semiotic laboratory capable of meticulously describing some characteristics of the cultures from which it comes and for which it is intended. In it, the role of the face is preeminent and assumes relevance both from a diegetic and a formal point of view. A face which makes itself a sign and is articulated in a dialectic between the syntagmatic and the paradigmatic axis, finding expression as an aspectual device, establishing a peculiar semiotic procedure of absentia in praesentia, and highlighting an eminently enunciative dimension of the textual genre. Thus a facial semiotics of pornography becomes to all effects a cultural semiotics, which through the exploration of a transversal genre – both in its mainstream and more niche actualizations – produces significant results in defining how cultures of the face, including extrapornographic ones, delineate themselves. The aim of this article is to verify this peculiar facial semiotics through a case history that stretches from traditional to contemporary pornography, also analysing the “facial pornography” website beautifulagony.com and the visual works of some contemporary artists.
Augmented facets: A semiotics analysis of augmented reality facial effects
Authors: Biggio Federico
Published: February 2022

Augmented reality facial effects represent a new trend in social media communication based on ‘short forms’. The article proposes a tripartite analysis: a semiotic analysis of digital facial effects used to empower the natural users’ faces; a deconstructionist analysis of Spark by Meta, one of the major software applications to create such effects and, finally, a critical reflection on the practices prescribed by Spark and the stereotypical aesthetics of augmented selfies. The conclusion states that such forms of augmented reality effects must be conceived not as oriented to the cognitive improvement of users’ performance but rather as forms of users’ empowerment and self-awareness.
Face and trust: A semiotic inquiry into influencers, money, and amygdala
Authors: Bankov Kristian
Published: February 2022

After the cultural explosion of Web 2.0, digital culture reveals an apparently semiotic paradox associated with the incredibly widespread use of images of faces, while at the same time the reason to trust in the authenticity of these faces is constantly declining. This is because graphic technology has made the sophisticated manipulation of images both possible and easy. After a review of the existing semiotic models and considerations of trust, I am proposing a new approach which emphasizes the value-generating properties of trust by analogy with the money sign, seen as “trust inscribed”. Research from the neurosciences supports the hypothesis that the trustworthiness of the face is judged pre-reflexively and primordially. This, therefore, means that a trustworthy face is a premise for more successful communication than an untrustworthy one, notwithstanding the object of discussion and the cultural context. An example concerning social media influencers serves to show that in the internet-dominated globalizing culture, trustworthy faces are a multipurpose communicative asset that makes a difference.
SOME ASPECTS OF THE WORLDVIEW FOUNDATIONS OF BIOETHICS
Authors: BESTAEVA E. , TEDEEVA U.
Published: February 2022

The purpose of the work is to determine the specifics of the worldview foundations of bioethics, their structure, nature and essence of man in the context of the “new experience” in the field of biotechnology. Research methods - philosophical and general logical.”New experience” in the field of biotechnology, as a stimulating discussion of anthropological, axiological and social problems, must be guided by the strategy of personal preservation and the methodology of human integrity and have value-worldview attitudes as real prerequisites. In the new ethics, the fundamental principles of two historically established systems - individualism and conciliarism (collectivism) are considered in the form of complement, not contradictory. We are only talking about their ratio and the degree of demand. At the same time, the state and society, and not “personal law”, are of decisive importance.
HISTORICAL AND PHILOSOPHICAL ASPECT OF THE ROLE AND IMPORTANCE OF ETHICS IN THE SYSTEM OF MODERN EDUCATION
Authors: BESTAEVA E.
Published: February 2022

The article examines the issues of ethics in the educational process in the historical and philosophical development. The main attention is focused on the transformations taking place in the field of economics, science and technology, the meaning and significance of education, which is aimed at the formation of a morally oriented personality, is being revised in a new way. The need for ethical knowledge comes to the fore in the modern educational process, which is aimed at the formation of moral values of the younger generation.
Difficult legacy in a close relationship. Sexual satisfaction, relationship satisfaction, and body image in patients with BRCA mutation after prophylactic mastectomy and/or adnexectomy.
Authors: Michałowska Sylwia
Published: February 2022

Aim of the study

Continuous scientific progress and the development of genetics have opened up new possibilities in the field of cancer prevention by detecting DNA mutations that increase oncological risk. In the case of high risk, special recommendations are addressed to the carriers of gene mutations and they concern, inter alia, surgical prophylactic procedures - mastectomy and adnexectomy. The aim of this study was to determine the relationship between sexual satisfaction, partner satisfaction and body assessment in women with the BRCA mutation depending on the preventive surgery performed by them that reduce cancer risk.

Subject or material and methods

The study involved 310 women with the BRCA genetic mutation and were healthy at the time of the study. The study lasted 7 months and the variables were measured using the Sexual Satisfaction Sale for Women (SSS WR15), the Matched Marriage Questionnaire (KDM-2), the Body Esteem Scale (BES) and the questionnaire enabling the collection of sociodemographic data and information related to cancer history and preventive operations performed.

Results

The conducted analysis showed significant differences between the patients depending on the preventive surgery performed in terms of sexual attractiveness, weight control and all dimensions of partner and sexual satisfaction.

Discussion

The results obtained are consistent with the results of studies conducted in other countries.

Conclusions

It has been proven that there are relationships between body assessment and sexual satisfaction as well as between body assessment and relationship satisfaction, and that there are differences in these areas between the groups of women who performed preventive mastectomy, adnexectomy, both procedures or none.