bluuebunny/crossref_metadata_2025 huggingface dataset:
22q11 Copy Number Variations in a Brazilian Cohort of Children with Congenital Heart Disorders
Authors: Floriani Maiara A. , Santos Andressa S. , Diniz Bruna L. , Glaeser Andressa B. , Gazzola Zen Paulo R. , Machado Rosa Rafael F.
Published: July 2022

Introduction: Congenital heart disease (CHD) is the most common type of congenital defect reported to be one of the leading causes of mortality in the first year of life. Microdeletion and microduplication syndromes (MMS) are associated with cardiac malformations. Understanding which genetic factors are involved in these conditions directly impacts treatment decisions. We aimed to identify the occurrence of genetic alterations and their association with MMS in CHD pediatric patients evaluated in a reference service of Southern Brazil. Methods: Participants were recruited during 2010 in the intensive care unit of a pediatric hospital. MMs and regions of chromosome 22 were screened by SALSA MLPA Probemix P245 Microdeletion Syndromes-1A kit for detection of copy number variations (CNVs). Results: MMS were detected in 11 from 207 patients (5.3%). Heterozygous deletion in the 22q11.2 chromosome region was the most prevalent CNV (5 from 11 patients). Also, atypical RTDR1 deletion and 22q11.2 duplication were detected. MLPA was able to reveal microdeletions in SNRPN and NF1 genes in patients with a normal karyotype and FISH. Conclusion: Our study reports the prevalence and variability of genomic alterations associated with MMS in CHD pediatric patients. The results by MLPA are of great help in planning and specialized care.
Pacritinib Inhibition of IRAK1 Blocks Aberrant TLR8 Signalling by SARS-CoV-2 and HIV-1-Derived RNA
Authors: Campbell Grant R. , Rawat Pratima , Spector Stephen A.
Published: July 2022

Macrophages promote an early host response to infection by releasing pro-inflammatory cytokines such as interleukin (IL) 1β (IL-1β), tumour necrosis factor (TNF), and IL-6. One of the mechanisms through which cells sense pathogenic microorganisms is through Toll-like receptors (TLRs). IL-1 receptor-associated kinase (IRAK) 1, IRAK2, IRAK3, and IRAK4 are integral to TLR and IL-1 receptor signalling pathways. Recent studies suggest a role for aberrant TLR8 and NLRP3 inflammasome activation during both COVID-19 and HIV-1 infection. Here, we show that pacritinib inhibits the TLR8-dependent pro-inflammatory cytokine response elicited by GU-rich single-stranded RNA derived from SARS-CoV-2 and HIV-1. Using genetic and pharmacologic inhibition, we demonstrate that pacritinib inhibits IRAK1 phosphorylation and ubiquitination which then inhibits the recruitment of the TAK1 complex to IRAK1, thus inhibiting the activation of downstream signalling and the production of pro-inflammatory cytokines.
ÖRGÜTSEL ETİK İKLİM VE ÖRGÜTSEL SESLİLİK İLİŞKİSİNDE ÖRGÜTSEL BAĞLILIĞIN ARACILIK ROLÜ: BANDIRMA İLÇESİ’NDE BİR ARAŞTIRMA ÖRNEĞİ
Authors: ÖRÜCÜ Edip , HASIRCI Itır , BÖCEK Alper
Published: July 2022

Bu araştırmada, işletmelerde örgütsel sesliliği arttırmak amacıyla yola çıkılmıştır. Bu kapsamda örgütsel bağlılığın ve örgütsel etik iklimin etkileri incelenmiştir. Araştırmaya ilişkin veriler, anket yoluyla toplanmıştır. Bu araştırmanın evrenini 170 çalışanı olan Balıkesir’in Bandırma ilçesindeki bir yem makinaları üretim firması oluşturmaktadır. Yapılan çoklu korelasyon analizinin neticesinde örgütsel etik iklim ile örgütsel bağlılık arasında pozitif yönlü ve anlamlı bir ilişki, örgütsel bağlılık ile örgütsel seslilik arasında pozitif yönlü ve anlamlı bir ilişki, örgütsel etik iklim ile örgütsel seslilik arasında pozitif yönlü ve anlamlı ilişkilerin olduğu belirlenmiştir. Yapılan hiyerarşik regresyon analizinin neticesinde örgütsel etik iklimin örgütsel seslilik üzerindeki etkisinde örgütsel bağlılığın aracılık rolünün varlığı tespit edilmiştir. Bu sonuç, işletme yöneticilerine örgütsel sesliliği arttırarak, işletme performanslarının yükseltilmesine katkı sağlayacaktır.
Two new species of the braconid wasp genus Bracon (Braconinae) from Los Tuxtlas region in Veracruz, Mexico, reared from fruits of three species of Lauraceae
Authors: RODRÍGUEZ-SÁNCHEZ EDNA , GIRALDO-KALIL LAURA J. , QUICKE DONALD L. J. , ZALDÍVAR-RIVERÓN ALEJANDRO
Published: July 2022

Two new species belonging to the braconid genus Bracon (Braconinae) are described from the tropical rainforest of Los Tuxtlas in the state of Veracruz, Mexico, B. laurae sp. nov. and B. rosamondae sp. nov. These species are morphologically similar and were reared from fruits of three Lauraceae species, Damburneya ambigens, D. salicifolia and Nectandra turbacensis. However, comparison of their DNA barcoding locus and a fragment of the nuclear ribosomal 28S gene confirmed their allospecificity. These two species share a number of morphological features with the two described Neotropical Bracon species that are known to be phytophagous (seed predators), B. phytophagus Quicke and B. zuleideae Perioto & Lara. We therefore propose a new species-group for the above four species, the B. phytophagus Quicke species-group, and suggest that the two newly described species also have a phytophagous feeding strategy.
Fighting for abortion rights: Strategies aimed at managing stigma in a group of Italian pro-choice activists
Authors: Giovannelli Ilaria , Mannarini Terri , Spaccatini Federica , Pacilli Maria Giuseppina
Published: July 2022

Despite societal changes in Western countries, abortion continues to be morally stigmatized. While research on abortion stigma targeted both at people who seek or voluntarily terminate their pregnancy and abortion providers has been conducted, stigma directed at those who advocate abortion rights has remained under-researched. The purpose of this study was to deepen understandings of abortion stigma in relation to Italian cisgender female pro-choice activists. Accordingly, a qualitative study was conducted to examine how participants experienced, perceived, and internalized stigma, as well as the strategies they employed to manage it. The sample included 34 Italian cisgender female pro-choice activists who were actively engaged in movements at the time of the study, including organizations or unions that publicly defend the right to abort. The findings revealed that participants perceive they are targets of negative stereotyping and behaviors. Nevertheless, they do not internalize the stigma and use different strategies to manage it, such as speaking openly about their activism.
Financing warfare in ancient India: 1500 BCE–circa 800 CE
Authors: Roy Kaushik
Published: July 2022

In this essay, I attempt to build a typology of how warfare was financed in ancient India. During the period discussed in this article (1500 BCE–800 CE), most of the polities of the subcontinent followed continental strategy. Hence, they focused on maintaining armies rather than navies. Loot and plunder were adequate for maintaining irregular forces and mercenaries temporarily. Some polities which depended on taxing overseas commerce and gathering tributes proved to be rickety. For maintaining a standing disciplined, trained and loyal army, a regular income in cash from taxation of settled agriculture with the aid of a centralised hierarchical bureaucracy was necessary.
Subfertile patients underestimate their risk factors of reprotoxic exposure
Authors: Nouiakh Nadia , Sunyach Claire , Jos Sarah-Lyne , Sari-Minodier Irène , Metzler-Guillemain Catherine , Courbiere Blandine , Bretelle Florence , Perrin Jeanne
Published: July 2022

Background

Exposure of men and women to environmental reprotoxic agents is associated with impaired fertility and pregnancy rates after assisted reproductive treatment (ART). Nevertheless, such exposures are generally not systematically assessed in current practice before ART and subfertile men are generally less explored than women. Our objective was to study subfertile men and women’s level of knowledge about reprotoxic agents, their perception of their own risk factors and the correlation between perceived and identified circumstances of exposure.

Results

In our public university hospital, 390 subfertile patients (185 men and 185 women) requiring assisted reproduction technique (ART) treatment, completed a self-report questionnaire before consultation, in order to assess patients’ knowledge of reprotoxic exposures, sources of information about them and perception of their own circumstances of exposure. Then a standardized questionnaire was used by the physician during the consultation to estimate domestic, environmental and occupational risk factors of reprotoxic exposures (RFRE). We compared the patients’ perception of exposure with the estimated RFRE.

The reprotoxic agents knowledge score of patients was 61%. Their main sources of information were the media (40%), the internet (22%) and gynecologists (15%). The standardized questionnaire identified RFRE in 265/390 patients (68%); risk factor was statistically more frequent in men (77%) than in women (59%) (p < 0.05). In total, 141 of the 265 patients with identified RFRE (53%) were aware of their risk factor of reprotoxic exposure.

Conclusion

We identified risk factors of reprotoxic exposures in the majority of subfertile patients, more frequently in men than in women, and half of patients were not aware of their exposures. Patients’ main sources of information were extra medical. Efforts should be made to inform patients, especially men, about potential reprotoxic exposure and to enhance medical training about reprotoxic agents, as recommended by international guidelines. The detection and correction of environmental exposures in subfertile men could improve their fecundity, but also their general health, which has been shown to be poorer than health of fertile men.
Genomic analysis of Listeria monocytogenes from US food processing environments reveals a high prevalence of QAC efflux genes but limited evidence of their contribution to environmental persistence
Authors: Daeschel Devin , Pettengill James B. , Wang Yu , Chen Yi , Allard Marc , Snyder Abigail B.
Published: July 2022

Background

Quaternary ammonium compound (QAC) efflux genes increase the minimum inhibitory concentration ofListeria monocytogenes(Lm) to benzalkonium chloride sanitizer, but the contribution of these genes to persistence in food processing environments is unclear. The goal of this study was to leverage genomic data and associated metadata for 4969 Lmisolates collected between 1999 and 2019 to: (1) evaluate the prevalence of QAC efflux genes amongLmisolates from diverse US food processors, (2) use comparative genomic analyses to assess confounding factors, such as clonal complex identity and stress tolerance genotypes, and (3) identify patterns in QAC efflux gene gain and loss among persistent clones within specific facilities over time.

Results

The QAC efflux gene cassettebcrABCwas present in nearly half (46%) of all isolates. QAC efflux gene prevalence among isolates was associated with clonal complex (𝛘2 < 0.001) and clonal complex was associated with the facility type (𝛘2 < 0.001). Consequently, changes in the prevalence of QAC efflux genes within individual facilities were generally attributable to changes in the prevalence of specific clonal complexes. Additionally, a GWAS and targeted BLAST search revealed that clonal complexes with a high prevalence of QAC efflux genes commonly possessed other stress tolerance genes. For example, a high prevalence ofbcrABCin a clonal complex was significantly associated with the presence of the SSI-1 gene cluster (p < 0.05). QAC efflux gene gain and loss were both observed among persistent populations ofLmin individual facilities, suggesting a limited direct role for QAC efflux genes as predictors of persistence.

Conclusion

This study suggests that although there is evidence that QAC efflux genes are part of a suite of adaptations common amongLmisolated from some food production environments, these genes may be neither sufficient nor necessary to enhance persistence. This is a crucial distinction for decision making in the food industry. For example, changes to sanitizer regimen targeting QAC tolerance would not address other contributing genetic or non-genetic factors, such as equipment hygienic design which physically mediates sanitizer exposure.
Aldehyde dehydrogenase superfamily in sorghum: genome-wide identification, evolution, and transcript profiling during development stages and stress conditions
Authors: Islam Md. Sifatul , Mohtasim Munira , Islam Tahmina , Ghosh Ajit
Published: July 2022

Background

Aldehyde dehydrogenases (ALDHs) are a family of NAD(P)+dependent enzymes that detoxify aldehydes by promoting their oxidation to respective carboxylic acids. The role of ALDH enzymes in various plant species has been extensively studied, revealing their critical role in salinity, drought, heat, and heavy metal stress tolerance. Despite their physiological significance,ALDHgenes inSorghum bicolorhave yet to be studied thoroughly.

Results

In this study, a total of 19ALDHgenes have been identified that have been grouped into ten families based on the criteria of theALDHgene nomenclature committee. Segmental duplication assisted more in the enhancement ofSbALDHgene family members than tandem duplication. All the identified SbALDH members made a cluster with monocot rice and maize in the phylogenetic tree rather than dicot species, suggesting the pre-eudicot-monocot separation of the ALDH superfamily members. The gene structure and protein domain were found to be mostly conserved in separate phylogenetic classes, indicating that each family played an important role in evolution. Expression analysis revealed that severalSbALDHs were expressed in various tissues, developmental stages, and in response to abiotic stresses, indicating that they can play roles in plant growth, development, or stress adaptation. Interestingly, the majority of theSbALDHgenes were found to be highly responsive to drought stress, and theSbALDH18B1 transcript showed maximum enhancement in all the stress conditions. The presence of cis-acting elements (mainly ABRE and MBS) in the promoter region of these genes might have a significant role in drought tolerance.

Conclusions

Our findings add to the current understanding, evolutionary history, and contribution of SbALDHs in stress tolerance, and smooth the path of further functional validation of these genes.
Improving the performance of a triage scale for chest pain patients admitted to emergency departments: combining cardiovascular risk factors and electrocardiogram
Authors: Casarin Chiara , Pirot Anne-Sophie , Gregoire Charles , Van Der Haert Laurence , Vanden Berghe Patrick , Castanares-Zapatero Diego , Dechamps Melanie
Published: July 2022

Background

The triage of patients presenting with chest pain on admission to the emergency department uses scales based on patient clinical presentation or an electrocardiogram (ECG). These scales have different sensitivity and specificity. Although a good sensitivity allows for the prompt identification of high-risk patients, specificity prevent ED overcrowding. Moreover, ECG at triage avoids missing ST elevation myocardial infarction, which requires urgent revascularization. Our study therefore aimed to investigate whether a scale combining ECG and cardiovascular risk factors (CVRF) improves the diagnostic performance of ED chest pain triage scale.

Methods and results

In this prospective single-center observational study involving 505 patients, the standard ECG-based FRENCH scale was compared to a scale combining the ECG-based FRENCH scale and the patients CVRF. The new scale was called the “modified” FRENCH. The accuracy of patient CVRF collection was evaluated by comparing the results of triage nurses and ED physicians.

Compared with the standard FRENCH scale, the modified FRENCH scale had an increased sensitivity (61% versus 75%) but a decrease in specificity (76% versus 64%) resulting in a similar diagnostic performance. Using CVRF collected by the ED physicians, the modified FRENCH scale had a sensitivity of 87% and a specificity of 56% with a significant improvement in his diagnostic performance compared with standard FRENCH scales. This improvement can be explained by an accurate collection of the CVRF by physicians compared with nurses, as suggested by the weak to moderate correlation between their respective data collection.

Conclusion

In conclusion, combining ECG and accurately collected cardiovascular risks factor improves the diagnostic performance of the ECG based chest pain triage in the ED.

Trial registration

Trial registration number: NCT03913767.
Machine learning approach for the prediction of 30-day mortality in patients with sepsis-associated encephalopathy
Authors: Peng Liwei , Peng Chi , Yang Fan , Wang Jian , Zuo Wei , Cheng Chao , Mao Zilong , Jin Zhichao , Li Weixin
Published: July 2022

Objective

Our study aimed to identify predictors as well as develop machine learning (ML) models to predict the risk of 30-day mortality in patients with sepsis-associated encephalopathy (SAE).

Materials and methods

ML models were developed and validated based on a public database named Medical Information Mart for Intensive Care (MIMIC)-IV. Models were compared by the area under the curve (AUC), accuracy, sensitivity, specificity, positive and negative predictive values, and Hosmer–Lemeshow good of fit test.

Results

Of 6994 patients in MIMIC-IV included in the final cohort, a total of 1232 (17.62%) patients died following SAE. Recursive feature elimination (RFE) selected 15 variables, including acute physiology score III (APSIII), Glasgow coma score (GCS), sepsis related organ failure assessment (SOFA), Charlson comorbidity index (CCI), red blood cell volume distribution width (RDW), blood urea nitrogen (BUN), age, respiratory rate, PaO2, temperature, lactate, creatinine (CRE), malignant cancer, metastatic solid tumor, and platelet (PLT). The validation cohort demonstrated all ML approaches had higher discriminative ability compared with the bagged trees (BT) model, although the difference was not statistically significant. Furthermore, in terms of the calibration performance, the artificial neural network (NNET), logistic regression (LR), and adapting boosting (Ada) models had a good calibration—namely, a high accuracy of prediction, with P-values of 0.831, 0.119, and 0.129, respectively.

Conclusions

The ML models, as demonstrated by our study, can be used to evaluate the prognosis of SAE patients in the intensive care unit (ICU). Online calculator could facilitate the sharing of predictive models.
Induction therapy and outcome of proliferative lupus nephritis in the top end of Northern Australia – a single centre study retrospective study
Authors: Xu Chi , Goh Kim Ling , Abeyaratne Asanga , Priyadarshana Kelum
Published: July 2022

Background

Lupus nephritis is a common manifestation of Systemic Lupus Erythematosus. Mycophenolate is recommended by guidelines for induction therapy in patients with proliferative lupus nephritis and nephrotic range proteinuria Class V lupus nephritis. Indigenous Australians suffer disproportionally from systemic lupus erythematosus compared to non-Indigenous Australians (Anstey et al., Aust N Z J Med 23:646–651, 1993; Segasothy et al., Lupus 10:439–444, 2001; Bossingham, Lupus 12:327–331, 2003; Grennan et al., Aust N Z J Med 25:182–183, 1995).

Methods

We retrospectively identified patients with newly diagnosed biopsy-proven class III lupus nephritis, class IV lupus nephritis and class V lupus nephritis with nephrotic range proteinuria from 1st Jan 2010 to 31st Dec 2019 in our institution and examined for the patterns of prescribed induction therapy and clinical outcome. The primary efficacy outcome of interest was the incidence of complete response (CR) and partial response (PR) at one-year post diagnosis as defined by the Kidney Disease: Improving Global Outcome (KDIGO) guideline. Secondary efficacy outcome was a composite of renal adverse outcome in the follow-up period. Adverse effect outcome of interest was any hospitalisations secondary to infections in the follow-up period. Continuous variables were compared using Student’s t-test or Mann–Whitney U-test. Categorical variables were summarised using frequencies and percentages and assessed by Fisher’s exact test. Time-to-event data was compared using the Kaplan–Meier method and Log-rank test. Count data were assessed using the Poisson’s regression method and expressed as incident rate ratio.

Results

Twenty of the 23 patients included in the analysis were managed with mycophenolate induction upfront. Indigenous Australian patients (N = 15), compared to non-Indigenous patients (N = 5) received lower cumulative dose of mycophenolate mofetil over the 24 weeks (375 g vs. 256 g, p < 0.05), had a non-significant lower incidence of complete remission at 12 months (60% vs. 40%, p = 0.617), higher incidence of composite renal adverse outcome (0/5 patients vs. 5/15 patients, p = 0.20) and higher incidence of infection related hospitalisations, (incident rate ratio 3.66, 95% confidence interval 0.89–15.09, p = 0.073).

Conclusion

Mycophenolate as upfront induction in Indigenous Australian patients were associated with lower incidence of remission and higher incidence of adverse outcomes. These observations bring the safety and efficacy profile of mycophenolate in Indigenous Australians into question.
Microvascular decompression in trigeminal neuralgia with the offending artery transfixing the nerve: a case report
Authors: Zhang Xinyu , Li Yang , Zhou Mi , Wei Zhenqing
Published: July 2022

Background

An anterior inferior cerebellar artery (AICA) that crosses the right trigeminal nerve is an uncommon arterial anatomic variation. In this anatomical position, it is difficult to separate or move the offending blood vessels and nerves. We report an uncommon case of trigeminal neuralgia (TN) caused by compression of the trigeminal ganglion by a branch of the AICA.

Case presentation

A 34-year-old man with 5 years history who complained of pain on the right side of the face (area V1). The symptoms gradually worsened, and the pain episodes became intense and frequent. Magnetic resonance imaging (MRI) of the cerebrum showed a small blood vessel passing through the right trigeminal nerve. Microvascular decompression (MVD) was performed,because medication was ineffective. Intraoperative exploration confirmed that the vessel which was a branch of the AICA passing through the right trigeminal nerve. As while the artery was temporarily clipped, electrophysiological monitoring showed a decrease in the amplitude of nerve activity. As the artery was considered too important to be sacrificed, the space between the nerves was enlarged mildly, the artery was liberated, the Teflon implant was shredded and placed between the artery branches and nerve to make the blood vessels as perpendicular as possible to the nerve. The patient had no neurological dysfunction and no pain after 8 months of follow-up.

Conclusion

MVD is an effective treatment for artery-induced trigeminal nerve compression, but we report a novel procedure that avoids the complication of facial numbness caused by cutting the offending vessels and incision of the trigeminal nerve.
Association between the cut-off value of the first trimester fasting plasma glucose level and gestational diabetes mellitus: a retrospective study from southern China
Authors: Tong Jia-Ning , Chen Yi-Xuan , Guan Xiao-Nian , Liu Kan , Yin Ai-Qi , Zhang Hua-Fan , Wu Lin-Lin , Niu Jian-Min
Published: July 2022

Purpose

Our previous studies have suggested that the first trimester fasting plasma glucose (FPG) level is associated with gestational diabetes mellitus (GDM) and is a predictor of GDM. The aim of the present study was to provide valuable insights into the accuracy of the first trimester FPG level in the screening and diagnosis of GDM in southern China.

Methods

This retrospective study included pregnant women who had their first trimester FPG level recorded at 9–13+6 weeks and underwent screening for GDM using the 2-h 75 g oral glucose tolerance test (OGTT) between the 24th and 28th gestational weeks. Differences between the GDM and non-GDM groups were assessed by Student’s t test and the chi-squared test according to the nature of the variables. A restricted cubic spine was used to explore the relationship between the first trimester FPG level and the odds ratio (OR) of GDM in pregnant women. Cut-off values of first trimester FPG were determined using receiver operating characteristic (ROC) curves and the area under the curve (AUC), and 95% confidence intervals (CIs), the positive predictive value (PPV) and the negative predictive value (NPV) were calculated.

Results

The medical records of 28,030 pregnant women were analysed, and 4,669 (16.66%) of them were diagnosed with GDM. The average first trimester FPG level was 4.62 ± 0.37 mmol/L. The OR of GDM increased with increasing first trimester FPG levels and with a value of first trimester FPG of approximately 4.6 mmol/L, which was equal to 1 (Chi-Square = 665.79, P < 0.001), and then started to increase rapidly afterwards. The ROC curve for fasting plasma glucose in the first trimester (4.735 mmol/L) for predicting gestational diabetes mellitus in pregnant women was 0.608 (95% CI: 0.598–0.617), with a sensitivity of 0.490 and a specificity of 0.676.

Conclusion

Based on the research, we recommend that all pregnant women undergo FPG testing in the first trimester, particularly at the first antenatal visit. Furthermore, we suggest that the risks of GDM should be given increased attention and management as soon as the first trimester FPG value is more than 4.7 mmol/L. First trimester FPG levels should be considered a screening marker when diagnosing GDM in pregnant women but this needs to be confirmed by more prospective studies. These factors may have a significant impact on the clinical treatment of pregnant women.
Diabetic retinopathy with extensively large area of capillary non-perfusion: characteristics and treatment outcomes
Authors: Huang Zijing , Qiu Kunliang , Yi Jingsheng , Lin Hongjie , Zheng Dezhi , Huang Dingguo , Zhang Guihua , Chen Haoyu , Zheng Jianlong , Wang Yifan , Fang Danqi , Chen Weiqi
Published: July 2022

Background

Capillary non-perfusion is an important characteristic for diabetic retinopathy (DR) indicating microvascular damage and ischemia. Data on the description and treatment outcomes of DR with large area of non-perfusion are lacking to date. We aim to describe the characteristics and treatment outcomes in a series of patients with DR who presented extensively large area of capillary non-perfusion (LACNP).

Methods

Fundus fluorescein angiograms from medical charts in patients diagnosed with DR between Jan 2017 and Dec 2019 were retrospectively reviewed. Clinical data in eyes with LACNP including imaging and laboratory findings at the first presentation were analyzed. The LACNP was defined as over 70% area of capillary non-perfusion throughout the whole image retina. The mean follow-up duration was 12.4 ± 16.7 months. Follow-up data including extensive pan-retinal photocoagulation and surgical intervention and treatment outcomes were evaluated.

Results

A total of 43 eyes in 24 patients with LACNP were included, accounting for 3.3% of DR populations in the same period. The overall percentage of non-perfusion area was 79.1 ± 8.1%. All patients received proper control of diabetes and hypertension, and extensive pan-retinal laser photocoagulation. During the follow-up periods, 20 eyes (46.5%) developed severe neovascular complications, of which 15 eyes (34.9%) underwent vitrectomy and/or anti-glaucoma surgeries. Conservative therapies including glycemic control and supplemental laser photocoagulation were conducted in 23 eyes (53.5%) without neovascular complications. In the final follow-up, best corrected visual acuity improved or maintained stable in 19 eyes (44.2%) while deteriorated in 24 eyes (55.8%).

Conclusions

The presence of LACNP is the hallmark of advanced DR and often indicates a poor visual outcome, although aggressive treatments may slow DR progression and maintain central vision for some time.
The coexistence of obesogenic behaviors among Brazilian adolescents and their associated factors
Authors: da Silva Thales Philipe Rodrigues , Matozinhos Fernanda Penido , Gratão Lúcia Helena Almeida , Rocha Luana Lara , Inácio Monique Louise Cassimiro , de Freitas Oliveira Cristiane , Rangel de Oliveira Tatiana Resende Prado , Mendes Larissa Loures
Published: July 2022

Background

The prevalence of obesity in adolescents has increased significantly in recent years. The growth of obesity is motivated by the association with modifiable behaviors, however, this behavioral are commonly evaluated individually, not considering the possibility of these factors coexisting in the individual. The purpose of this essay was to identify the coexistence of obesogenic behaviors among Brazilian adolescents and to assess the factors associated with the presence of these behaviors.

Methods

This a cross-sectional, national, school-based study with data from the Study of Cardiovascular Risks in Adolescents (ERICA), totaling a sample of 71,552 Brazilian adolescents. To identify the coexistence of obesogenic behaviors in adolescents, the Principal Component Analysis has been performed. To assess the association between factors that influence the coexistence of modifiable behaviors in the pattern of obesogenic behavior, logistic regression was used. The magnitude of the associations was estimated by the Odds Ratio (OR), with the respective 95% confidence intervals (95%CI).

Results

The component was characterized by a higher percentage of ultra-processed food intake, longer in front of screens, having a habit of snacking in front of the television, and not having the habit of eating breakfast. In the adjusted logistic model, it shows that female adolescents and who declare themselves black are more likely to belong to the third tertile of the pattern of obesogenic behavior. As for teenagers who sometimes or almost always or always have lunch or dinner with parents or guardians, who have longer hours of sleep and who live in economically disadvantaged regions have reduced chances of belonging to the third tertile of the pattern of obesogenic behavior.

Conclusion

The identification of obesogenic behavior patterns allows assertive interventions to eliminate or reduce these changeable behaviors, also aiming at the possibility of reducing obesity among adolescents.
Association between total bilirubin and bone mineral density level in adolescents
Authors: Wu Jing , Su Jiali , Wang Yangyang , Chen Jianfeng , Shang Yuanyuan , Li Jing
Published: July 2022

Background

Increasing bone mass accumulation in adolescence and obtaining greater peak bone mass is one of the effective methods to prevent osteoporosis in the future. We aimed to examine the association between total bilirubin and bone mineral density (BMD) level in adolescents.

Methods

We used the data from 2005–2010 and 2013–2014 cycles of National Health and Nutrition Examination Survey (NHANES). The BMD levels in the region of lumbar spine and femoral regions, including total femur, femoral neck, trochanter, and intertrochanter were measured. Univariable and multivariable linear regression model were used to assess the relationship between total bilirubin concentration and BMD.

Results

A total of 3741 participants aged 12–19 years were ultimately included in the study. There were 1997 (53.38%) males and 1744 (46.62%) females. Univariate analysis results showed that age, sex, race, education, income, body mass index, dietary calcium intake, and diabetes were correlated with BMD levels. Compared with the lowest quartile of total bilirubin concentration, the highest quartile of total bilirubin concentration was positively associated with BMD levels in the regions of total femur (β = 0.036, 95% CI = 0.021 to 0.050,P < 0.001), femur neck (β = 0.030, 95% CI = 0.016 to 0.044,P < 0.001), trochanter (β = 0.033, 95% CI = 0.019 to 0.046,P < 0.001), intertrochanter (β = 0.040, 95% CI = 0.023 to 0.056,P < 0.001), and lumbar spine (β = 0.032, 95% CI = 0.018 to 0.045,P < 0.001). We also observe the same trend in sensitivity analysis (Pfor trend < 0.001).

Conclusion

Our study demonstrated that total bilirubin concentration was positively associated with BMD levels in adolescents in United States. Total bilirubin concentration might be a protective marker against bone loss in adolescents.
A case report and review of acute cholangitis with septic shock induced by Edwardsiella tarda
Authors: Ding Yue , Men Wanqi
Published: July 2022

Background

Edwardsiella tarda (E. tarda) is a gram-negative facultative anaerobic bacterium. Gastroenteritis is the most common manifestation of E. tarda infection. However, parenteral infections can occur in immunodeficient hosts, as well as hepatobiliary diseases, malignancies, and/or diabetes. The prognosis of sepsis caused by E. tarda is very worse, with a mortality rate of 38%. We report the occurrence of acute cholecystitis with septic shock and E. tarda bloodstream infection.

Case presentation

A 64-year-old male with acute cholecystitis secondary to hepatitis B virus infection showed fever and sudden upper abdominal pain. On arrival, right upper abdominal pain, nausea, vomiting, fever, and jaundice were observed. Computed tomography showed common bile duct stones and gallbladder stones. Choledocholithiasis with acute cholangitis was diagnosed and treated surgically. Due to septic shock, a blood culture was assessed showing E. tarda as the main pathogen. Choledocholithotomy, T-tube drainage, cholecystectomy, and intravenous antibiotic treatment after the operation. The patient recovered smoothly after the operation.

Conclusions

Although E. tarda infection is extremely rare, it can cause rapid episodes of rapidly progressive and life-threatening disease, as well as intestinal and parenteral infections. If necessary, early surgical treatment of parenteral infection should be considered and antibiotics should be used in time.
Basal and dynamic relationships between serum anti-Müllerian hormone and gonadotropins in patients with functional hypothalamic amenorrhea, with or without polycystic ovarian morphology
Authors: Hager Marlene , Ott Johannes , Marschalek Julian , Marschalek Marie-Louise , Kinsky Clemens , Marculescu Rodrig , Dewailly Didier
Published: July 2022

Background

To evaluate in women with functional hypothalamic amenorrhea (FHA), whether there is a difference between patients with and without polycystic ovarian morphology (PCOM) concerning the response to a gonadotropin releasing hormone (GnRH) stimulation test and to pulsatile GnRH treatment.

Methods

In a retrospective observational study, 64 women with FHA who underwent a GnRH stimulation test and 32 age-matched controls without PCOM were included. Pulsatile GnRH treatment was provided to 31 FHA patients and three-month follow-up data were available for 19 of these.

Results

Serum levels of gonadotropins and estradiol were lower in FHA women than in controls (p < 0.05). FHA patients revealed PCOM in 27/64 cases (42.2%). FHA patients without PCOM revealed lower anti-Müllerian hormone (AMH) levels than controls (median 2.03 ng/mL, IQR 1.40–2.50, versus 3.08 ng/mL, IQR 2.24–4.10, respectively,p < 0.001). Comparing FHA patients with and without PCOM, the latter revealed lower AMH levels, a lower median LH increase after the GnRH stimulation test (240.0%, IQR 186.4–370.0, versus 604.9%, IQR 360.0–1122.0;p < 0.001) as well as, contrary to patients with PCOM, a significant increase in AMH after three months of successful pulsatile GnRH treatment (median 1.69 ng/mL at baseline versus 2.02 ng/mL after three months of treatment;p = 0.002).

Conclusions

In women with FHA without PCOM, the phenomenon of low AMH levels seems to be based on relative gonadotropin deficiency rather than diminished ovarian reserve. AMH tended to rise after three months of pulsatile GnRH treatment. The differences found between patients with and without PCOM suggest the former the existence of some PCOS-specific systemic and/or intra-ovarian abnormalities.
Acupuncture versus pharmacological conversation in treatment of atrial fibrillation in a randomized controlled trial: a systemic review and meta-analysis
Authors: Li Yibing , Song Jinming , Wu Bangqi , Wang Xuhui , Han Lin , Han Zhenzhen
Published: July 2022

Objective

This study aimed to investigate the effect of conventional drugs combined with acupuncture therapy on the conversion of sinus rhythm in patients with atrial fibrillation.

Methods

We searched databases, such as PubMed, Embase, WOS, Cochrane, CNKI (China National Knowledge Infrastructure), Wan fang Data, VIP, and CBM to collect data in randomized controlled trials of acupuncture included patients with atrial fibrillation. Publication time was limited from the beginning to May 15, 2021. The primary outcome is the number of participants who converted successfully.

Results

A total of 11 papers were included in this study. The combined effect indicated that acupuncture significantly effectively benefitted the patients with atrial fibrillation (RR = 1.208, 95% CI 1.123, 1.298,P < 0.001). Further subgroup analysis of persistent and paroxysmal atrial fibrillation and the timing of acupuncture suggested that the addition of acupuncture was not statistically significant in the treatment of persistent AF compared to the control group (RR = 1.147, 95% CI 0.811, 1.623P = 0.147). The combination of acupuncture was more effective in paroxysmal AF RR = 1.148 (95% CI 1.064, 1.239)P < 0.001. In addition, when the acupuncture time was limited to 20 min, it had the best treatment effect (RR = 1.510, 95% CI 1.25, 1.82).

Conclusions

The combination of pharmacological resuscitation with acupuncture significantly improved the conversion of paroxysmal atrial fibrillation compared to pharmacological resuscitation only. The most significant benefit was achieved with an acupuncture duration of < 20 min. Thus, the combination of acupuncture could be considered in clinical practice for the resuscitation of patients with atrial fibrillation.
Evaluation of a model of online, facilitated, peer group supervision for dietitians working in eating disorders
Authors: Davis Amanda , Meloncelli Nina , Hannigan Amy , Ward Warren
Published: July 2022

Background

The recently publishedAustralia and New Zealand Academy of Eating Disorders(ANZAED)practice and training standards for dietitians providing eating disorder treatmentrecommended dietitians working in eating disorders (EDs) seek further clinical experience, training, and supervision to provide effective evidence-informed treatment. Access to dietetic clinical supervision is problematic, secondary to limited trained supervisors, location, cost, and lack of organizational support. Demand for clinical supervision increased with the 2022 introduction of ANZAED credentialing for eating disorder (ED) clinicians in Australia and addition of the Eating Disorder Management Plan to the Medicare Benefits Scheme. In 2018, QuEDS piloted a model of online peer group supervision with the goal of increasing service capacity to provide ED-specific clinical supervision to dietitians. Positive evaluation of the pilot led to the rollout of QuEDS Facilitated Peer Supervision (QuEDS FPS) program which was evaluated for utility and acceptability.

Methods

By August 2021 five QuEDS FPS groups were established each with a maximum of 10 Queensland-based dietitians from public hospital, community, or private practice plus an additional Facilitator and Co-facilitator. A total of 76 participants enrolled in the program over the study period in addition to the 10 participants from the pilot program. Participant experience was evaluated with anonymous, voluntary surveys at baseline (59 responses), 6 months follow-up (37 responses), plus a one-off survey in August 2021 (50 responses). Pilot participant’s Baseline and Follow-up surveys were not included in this evaluation.

Results

Survey responses were positive across the four Kirkpatrick training evaluation domains of reaction, learning, behavior, and results. Respondents reported positive change to clinical practice (98%), including increased confidence to implement evidence-informed guidelines, and improved engagement with, and advocacy for, ED clients. Service capacity to provide supervision was increased by high participant to Facilitator ratios (10 participants to one Facilitator and one Co-facilitator) and recruitment of external Facilitators. Respondents indicated they would recommend QuEDS FPS to other dietitians and 96% planned to continue with the program.

Conclusions

QuEDS FPS program increases capacity to provide supervision with demonstrated positive impacts on dietitians’ confidence and ability to deliver dietetic interventions in the ED arena and, by inference, the dietetic care of people with an ED.
Increased CSF-decorin predicts brain pathological changes driven by Alzheimer’s Aβ amyloidosis
Authors: Jiang Richeng , Smailovic Una , Haytural Hazal , Tijms Betty M. , Li Hao , Haret Robert Mihai , Shevchenko Ganna , Chen Gefei , Abelein Axel , Gobom Johan , Frykman Susanne , Sekiguchi Misaki , Fujioka Ryo , Watamura Naoto , Sasaguri Hiroki , Nyström Sofie , Hammarström Per , Saido Takaomi C. , Jelic Vesna , Syvänen Stina , Zetterberg Henrik , Winblad Bengt , Bergquist Jonas , Visser Pieter Jelle , Nilsson Per
Published: July 2022

Cerebrospinal fluid (CSF) biomarkers play an important role in diagnosing Alzheimer’s disease (AD) which is characterized by amyloid-β (Aβ) amyloidosis. Here, we used two App knock-in mouse models, AppNL-F/NL-F and AppNL-G-F/NL-G-F, exhibiting AD-like Aβ pathology to analyze how the brain pathologies translate to CSF proteomes by label-free mass spectrometry (MS). This identified several extracellular matrix (ECM) proteins as significantly altered in App knock-in mice. Next, we compared mouse CSF proteomes with previously reported human CSF MS results acquired from patients across the AD spectrum. Intriguingly, the ECM protein decorin was similarly and significantly increased in both AppNL-F/NL-F and AppNL-G-F/NL-G-F mice, strikingly already at three months of age in the AppNL-F/NL-F mice and preclinical AD subjects having abnormal CSF-Aβ42 but normal cognition. Notably, in this group of subjects, CSF-decorin levels positively correlated with CSF-Aβ42 levels indicating that the change in CSF-decorin is associated with early Aβ amyloidosis. Importantly, receiver operating characteristic analysis revealed that CSF-decorin can predict a specific AD subtype having innate immune activation and potential choroid plexus dysfunction in the brain. Consistently, in AppNL-F/NL-F mice, increased CSF-decorin correlated with both Aβ plaque load and with decorin levels in choroid plexus. In addition, a low concentration of human Aβ42 induces decorin secretion from mouse primary neurons. Interestingly, we finally identify decorin to activate neuronal autophagy through enhancing lysosomal function. Altogether, the increased CSF-decorin levels occurring at an early stage of Aβ amyloidosis in the brain may reflect pathological changes in choroid plexus, present in a subtype of AD subjects.
Excellent removal of knob-into-hole bispecific antibody byproducts and impurities in a single-capture chromatography
Authors: Chen Serene W. , Hoi Kong Meng , Mahfut Farouq Bin , Yang Yuansheng , Zhang Wei
Published: July 2022

Bispecific antibodies (bsAbs) are therapeutically promising due to their ability to bind to two different antigens. However, the bsAb byproducts and impurities, including mispaired homodimers, half-antibodies, light chain mispairings, antibody fragments and high levels of high molecular weight (HMW) species, all pose unique challenges to their downstream processing. Here, using two knob-into-hole (KiH) constructs of bsAbs as model molecules, we demonstrate the excellent removal of bsAb byproducts and impurities in a single Protein A chromatography under optimized conditions, including hole–hole homodimer mispaired products which are physicochemically very similar to the target bsAbs and still present even with the use of the KiH format, though at reduced levels. The removal occurs through the incorporation of an intermediate low-pH wash step and optimal elution conditions, achieving ~ 60% monomeric purity increase in a single Protein A step, without the introduction of sequence-specific bsAb modifications to specifically induce differential Protein A binding. Our results also suggest that the higher aggregation propensity of bsAbs may cause aggregation during the column process, hence an optimization of the appropriate loading amount, which may be lower than that of monoclonal antibodies (mAbs), is required. With the use of loading at 50% of 10% breakthrough (QB10) at 6-min residence time, we show that an overall high monomer purity of 92.1–93.2% can be achieved with good recovery of 78.4–90.6% within one capture step, which is a significant improvement from a monomer purity of ~ 30% in the cell culture supernatant (CCS). The results presented here would be an insightful guidance to all researchers working on the purification process development to produce bispecific antibodies, especially for knob-into-hole bispecific antibodies.

Graphical Abstract
Caloric restriction-mimetics for the reduction of heart failure risk in aging heart: with consideration of gender-related differences
Authors: Pang Lei , Jiang Xi , Lian Xin , Chen Jie , Song Er-Fei , Jin Lei-Gang , Xia Zheng-Yuan , Ma Hai-Chun , Cai Yin
Published: July 2022

The literature is full of claims regarding the consumption of polyphenol or polyamine-rich foods that offer some protection from developing cardiovascular disease (CVD). This is achieved by preventing cardiac hypertrophy and protecting blood vessels through improving the function of endothelium. However, do these interventions work in the aged human hearts? Cardiac aging is accompanied by an increase in left ventricular hypertrophy, along with diastolic and systolic dysfunction. It also confers significant cardiovascular risks for both sexes. The incidence and prevalence of CVD increase sharply at an earlier age in men than women. Furthermore, the patterns of heart failure differ between sexes, as do the lifetime risk factors. Do caloric restriction (CR)-mimetics, rich in polyphenol or polyamine, delay or reverse cardiac aging equally in both men and women? This review will discuss three areas: (1) mechanisms underlying age-related cardiac remodeling; (2) gender-related differences and potential mechanisms underlying diminished cardiac response in older men and women; (3) we select a few polyphenol or polyamine rich compounds as the CR-mimetics, such as resveratrol, quercetin, curcumin, epigallocatechin gallate and spermidine, due to their capability to extend health-span and induce autophagy. We outline their abilities and issues on retarding aging in animal hearts and preventing CVD in humans. We discuss the confounding factors that should be considered for developing therapeutic strategies against cardiac aging in humans.