bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term consequences of COVID-19 on mental health and the impact of a physically active lifestyle: a narrative review
Authors: Roever Leonardo , Cavalcante Bruno Raphael Ribeiro , Improta-Caria Alex Cleber
Published: May 2023

Background

Coronavirus-19 disease (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Respiratory viruses damage not only the upper respiratory tract in humans, but also several different organs such as the brain. Some of the neurological consequences of COVID-19 reported are anosmia, headache, stroke, declined cognitive function, and impaired mental health, among others. People who had COVID-19 have a higher risk of sequelae in the central nervous system (CNS). However, it is not known which are all possible sequelae and how long will last the long-term effects of the COVID-19 pandemic on behavioral patterns and quality of life.

Aim

We intend to address the long-term impacts of COVID-19 on mental health and the relevance of physical exercise during the pandemic.

Methods

We conducted a literature search using PubMed to find the articles that were related to these themes.

Results

We found 23,489 papers initially, and then we applied the inclusion/exclusion criteria to narrow down our search to 3617 articles and selected 1380 eligible articles after a thorough reading of titles and abstracts. The findings indicated that COVID-19 impacted general mental health and led many not only hospitalized patients to develop cognitive decline, memory impairment, anxiety, sleep alterations, and depressive-like behavior. Furthermore, the fear of vaccines and their effects had negatively affected mental health and directly impacted mortality rates in unvaccinated COVID-19 patients.

Conclusions

Preventive measures must be undertaken, such as the vaccination of the entire population, vaccination hesitancy discouragement by creating awareness among individuals, and people’s engagement in a physically active lifestyle, since being physically active is a low-cost and effective measure to restore or inhibit the negative outcomes from COVID-19 on mental health.
Alternation in functional connectivity within default mode network after psychodynamic psychotherapy in borderline personality disorder
Authors: Amiri Saba , Mirfazeli Fatemeh Sadat , Grafman Jordan , Mohammadsadeghi Homa , Eftekhar Mehrdad , Karimzad Nazila , Mohebbi Maryam , Nohesara Shabnam
Published: May 2023

Background

Borderline personality disorder (BPD) is characterized by impairments in emotion regulation, impulse control, and interpersonal and social functioning along with a deficit in emotional awareness and empathy. In this study, we investigated whether functional connectivity (FC) within the default mode network (DMN) is affected by 1-year psychodynamic psychotherapy in patients with BPD.

Methods

Nine BPD patients filled out the demography, Interpersonal Reactive Index (IRI), Toronto Alexithymia Scale 20 (TAS 20), the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST), and the Borderline Evaluation Severity over Time (BEST) questionnaire. The BPD group (9F) and the control group (9F) had a mean ± SD age of 28.2 ± 5.3 years and 30.4 ± 6.1 years, respectively. BPD subjects underwent longitudinal resting-state fMRI before psychodynamic psychotherapy and then every 4 months for a year after initiating psychotherapy. FC in DMN was characterized by calculating the nodal degree, a measure of centrality in the graph theory.

Results

The results indicated that patients with BPD present with aberrant DMN connectivity compared to healthy controls. Over a year of psychotherapy, the patients with BPD showed both FC changes (decreasing nodal degree in the dorsal anterior cingulate cortex and increasing in other cingulate cortex regions) and behavioral improvement in their symptoms and substance use. There was also a significant positive association between the decreased nodal degree in regions of the dorsal cingulate cortex and a decrease in the score of the TAS-20 indicating difficulty in identifying feelings after psychotherapy.

Conclusion

In BPD, there is altered FC within the DMN and disruption in self-processing and emotion regulation. Psychotherapy may modify the DMN connectivity and that modification is associated with positive changes in BPD emotional symptoms.
Healthcare utilization and costs of singaporean youth with symptoms of depression and anxiety: results from a 2022 web panel
Authors: Chodavadia Parth , Teo Irene , Poremski Daniel , Fung Daniel Shuen Shung , Finkelstein Eric A.
Published: May 2023

Background

There is evidence that the prevalence of depression and anxiety among youth is increasing and that these factors contribute to high healthcare costs and poor school performance. The goal of this study is to provide up-to-date estimates of the prevalence and economic burden of depression and anxiety among youth in Singapore.

Methods

Using an existing web panel, 991 parents filled out the PHQ-4 screener on behalf of 1,515 youth. 104 of these parents whose children (ages 4 to 21) had symptoms consistent with depression or anxiety filled out a full survey with questions on mental health symptoms, school absences, school performance, and healthcare utilization. The survey was fielded between April and June 2022. Publicly available prices were used to estimate the cost associated with the observed rates of health service use.

Findings

Based on parental responses, 11.7% (95% CI:10.2 − 13.5%) of youth had symptoms consistent with depression and 12.8% (95% CI:11.2 − 14.6%) had symptoms consistent with anxiety. In total, 16.2% (95% CI:14.5 − 18.3%) were reported to have symptoms consistent with at least one of these conditions. These youths missed an average of 190 (95% CI: 126–254) hours of school per year due to their mental health conditions and parents reported that school and daily activities performance was significantly degraded. Per capita annual healthcare costs averaged S$10,250 (95% CI: 7,150–13,350), with 64% of youth receiving emergency or inpatient services. In aggregate, annual costs associated with these conditions were estimated to be S$1.2 billion (95% CI:S$1.1bn – S$1.4bn).

Interpretation

Even with significant potential for underreporting, these results reveal concerning rates of Singaporean youth with symptoms consistent with depression or anxiety, many of whom remain untreated. Results also reveal the short-term economic burden caused by these symptoms and hint at longer-term consequences resulting from poor school performance. This study should represent a call to action for Singapore to address poor mental health among youth.
Subgroups of perceptions and related behaviors during the COVID-19 lockdown: experience of adolescents in the PARIS birth cohort
Authors: Citerne Antoine , Roda Célina , Rancière Fanny , Momas Isabelle
Published: May 2023

Background

Adolescents may not all have reacted similarly to the COVID-19 lockdown. This study aimed to identify subgroups of perceptions in adolescents from the PARIS cohort during the first French lockdown, and to investigate whether adolescent behaviors differed according to these subgroups.

Methods

Online questionnaires were sent to 1,549 PARIS adolescents aged 13–17 years who reported on possible infection with SARS-CoV-2, their perceptions, and behaviors during lockdown. Ascending hierarchical clustering was performed on the perception variables. Associations of behaviors with perception clusters were analyzed using multivariable multinomial logistic regression.

Results

Three perception clusters were identified among 791 adolescents (response rate 51%). One cluster “happy” (39%) had good mental health and did not feel stressed during lockdown. Another cluster “unhappy” (19%) was mainly unhappy, felt stressed, suffered from overcrowded living conditions, and experienced deteriorating relationships with family members. A further cluster “intermediate” (42%) experienced moderate well-being and stress, felt more supported by family, and worried about the health of their relatives. Compared with the “happy” cluster, the unhappy adolescents were more affected by COVID-19, had difficulty doing school activities, spent more time on social networks and less time on video games, slept less, and reported a deterioration in their diet. Adolescents “intermediate” with moderate well-being were more often girls, spent more time on social networks, were more physically active, slept less, and more often reported eating fruit and vegetables and drinking alcohol.

Conclusions

Not all adolescents experienced lockdown in the same way. This study highlighted subgroups that differed in terms of well-being and health-related behaviors. These results should motivate public authorities to consider the benefit/risk ratio of implementing strict lockdowns by taking into account family disparities and inequities among adolescents.
Insights into the capability of the lignocellulolytic enzymes of Penicillium parvum 4-14 to saccharify corn bran after alkaline hydrogen peroxide pretreatment
Authors: Long Liangkun , Wang Wei , Liu Zhen , Lin Yuanxin , Wang Jing , Lin Qunying , Ding Shaojun
Published: May 2023

Background

Corn bran is a major agro-industrial byproduct from corn starch processing. It contains abundant arabinoxylan that can be converted into value-added chemicals via biotechnology. Corn bran arabinoxylan (CBAX) is one of the most recalcitrant xylans for enzymatic degradation due to its particular heterogeneous nature. The present study aimed to investigate the capability of the filamentous fungus Penicilliumparvum 4-14 to enzymatically saccharify CBAX and reveal the fungal carbohydrate-active enzyme (CAZyme) repertoire by genome sequencing and secretome analysis.

Results

CBAX1 and CBAX2 with different branching degrees, together with corn bran residue (CBR) were generated from corn bran after alkaline hydrogen peroxide (AHP) pretreatment and graded ethanol precipitation. The protein blends E_CBAX1, E_CBAX2, and E_CBR were produced by the fungus grown on CBAX1, CBAX2, or CBR, respectively. Under the optimal conditions, E_CBAX1 released more than 80% xylose and arabinose from CBAX1 and CBAX2. Almost complete saccharification of the arabinoxylans was achieved by combining E_CBAX1 and a commercial enzyme cocktail Cellic®CTec3. Approximately 89% glucose, 64% xylose, and 64% arabinose were liberated from CBR by E_CBR. The combination of E_CBR with Cellic®CTec3 enhanced the saccharification of CBR, with conversion ratios of 97% for glucose, 81% for xylose, and 76% for arabinose. A total of 376 CAZymes including plentiful lignocellulolytic enzymes were predicted in P.parvum based on the fungal genomic sequence (25.8 Mb). Proteomic analysis indicated that the expression of CAZymes in P.parvum varied between CBAX1 and CBR, and the fungus produced complete cellulases, numerous hemicellulases, as well as high levels of glycosidases under the culture conditions.

Conclusions

This investigation disclosed the CAZyme repertoire of P.parvum at the genomic and proteomic levels, and elaborated on the promising potential of fungal lignocellulolytic enzymes upon saccharification of corn bran biomass after AHP pretreatment.
Co-infection of dengue and Zika viruses mutually enhances viral replication in the mosquito Aedes aegypti
Authors: Lin Daniel Chieh-Ding , Weng Shih-Che , Tsao Po-Nien , Chu Justin Jang Hann , Shiao Shin-Hong
Published: May 2023

Background

The mosquito Aedes aegypti transmits two of the most serious mosquito-borne viruses, dengue virus (DENV) and Zika virus (ZIKV), which results in significant human morbidity and mortality worldwide. The quickly shifting landscapes of DENV and ZIKV endemicity worldwide raise concerns that their co-circulation through the Ae. aegypti mosquito vector could greatly exacerbate the disease burden in humans. Recent reports have indicated an increase in the number of co-infection cases in expanding co-endemic regions; however, the impact of co-infection on viral infection and the detailed molecular mechanisms remain to be defined.

Methods

C6/36 (Aedes albopictus) cells were cultured in Dulbecco's modified Eagle medium/Mitsuhashi and Maramorosch Insect Medium (DMEM/MM) (1:1) containing 2% heat-inactivated fetal bovine serum and 1× penicillin/streptomycin solution. For virus propagation, the cells were infected with either DENV serotype 2 (DENV2) strain 16681 or ZIKV isolate Thailand/1610acTw (MF692778.1). Mosquitoes (Ae. aegypti UGAL [University of Georgia Laboratory]/Rockefeller strain) were orally infected with DENV2 and ZIKV through infectious blood-feeding.

Results

We first examined viral replication activity in cells infected simultaneously, or sequentially, with DENV and ZIKV, and found interspecies binding of viral genomic transcripts to the non-structural protein 5 (NS5). When we challenged Ae. aegypti mosquitos with both DENV2 and ZIKV sequentially to probe similar interactions, virus production and vector susceptibility to infection were significantly enhanced.

Conclusions

Our results suggest that DENV2 and ZIKV simultaneously establishing infection in the Ae. aegypti mosquito vector may augment one another during replication. The data also implicate the homologous NS5 protein as a key intersection between the flaviviruses in co-infection, highlighting it as a potential target for vector control.
Loss of CpG island immunity to DNA methylation induced by mutation
Authors: Horsthemke Bernhard , Bird Adrian
Published: May 2023

The inheritance of acquired traits in mammals is a highly controversial topic in biology. Recently, Takahashi et al. (Cell 186:715–731, 2023) have reported that insertion of CpG-free DNA into a CpG island (CGI) can induce DNA methylation of the CGI and that this aberrant methylation pattern can be transmitted across generations, even after removal of the foreign DNA. These results were interpreted as evidence for transgenerational inheritance of acquired DNA methylation patterns. Here, we discuss several interpretational issues raised by this study and consider alternative explanations.
Comparison between percutaneous transthoracic co-axial needle CT-guided biopsy and transbronchial lung biopsy for the diagnosis of persistent pulmonary consolidation
Authors: Wang Juan , Zhang Tongyin , Xu Yanyan , Yang Meng , Huang Zhenguo , Lin Jie , Xie Sheng , Sun Hongliang
Published: May 2023

Background

Diagnosing persistent pulmonary consolidation still faces challenges. The purpose of this study is to compare the diagnostic yield and the complication rate between percutaneous transthoracic CT-guided coaxial needle biopsy (PTCNB) and transbronchial lung biopsy (TBLB) of persistent pulmonary consolidation.

Materials

From January 1, 2016, to December 31, 2020, we have retrospectively enrolled a total of 155 consecutive patients (95 males, 60 females) with persistent pulmonary consolidation who underwent both TBLB and PTCNB. According to the standard reference, the diagnostic yield, accuracy, sensitivity and specificity of PTCNB and TBLB were assessed and compared.

Results

According to the standard reference, the final biopsy diagnoses of 11 cases were confirmed true malignant based on the surgical resections, the remaining were confirmed by clinical and imaging follow-up for at least 12 months. The overall diagnostic accuracy, sensitivity and specificity of PTCNB for malignant diagnosis were 91.61%, 72.34% and 100%, whereas of TBLB were 87.74%, 59.57% and 100%. The diagnostic yield of PTCNB and TBLB were 50.32% and 25.16%, respectively. For the TBLB-based negative cases, PTCNB provided a definite diagnostic yield of 37.93%. There were 45 (29.03%), 22 (14.19%) and 13 (8.39%) patients who experienced pneumothorax, intrapulmonary hemorrhage and hemoptysis, respectively, in PTCNB, while there were only 5 (3.22%) cases of mild intraprocedural bleeding occurring in TBLB.

Conclusions

CT-guided co-axial needle biopsy is an effective and safe modality, associated with higher diagnostic yield and better diagnostic accuracy compared to transbronchial lung biopsy for malignancy presenting as persistent consolidation, especially as the complementary method for TBLB-based negative lung lesions.

Key Points

Both PTCNB and TBLB showed high diagnostic accuracy for malignancy.

PTCNB had a higher diagnostic yield than TBLB for persistent pulmonary consolidation.

PTCNB could provide a complementary diagnosis for TBLB-based negative lung consolidation.
Fermentation characteristics and radical scavenging capacities of ginseng berry kombucha fermented by Saccharomyces cerevisiae and Gluconobacter oxydans
Authors: Choi Eun Jung , Song Hee Ho , Ko Ka Young , Hong Ki-Bae , Suh Hyung Joo , Ahn Yejin
Published: May 2023

Kombucha is a healthy carbonated beverage made by fermenting tea extracts such as green tea and black tea through symbiotic culture of bacteria and yeast. In this study, fermentation characteristics and radical scavenging activity of ginseng berry kombucha (GBK) by Saccharomyces cerevisiae M-5 and Gluconobacter oxydans were measured. As fermentation time increased, pH decreased and titratable acidity increased. Reducing sugars decreased rapidly on day 3. Alcohol content increased dramatically during this period and then decreased. GBK showed increased radical scavenging activity and increased total flavonoid content on day 18 of fermentation compared to before fermentation. In particular, during GBK fermentation, the content of phenolic compounds such as gallic acid (2.09-fold) and chlorogenic acid (2.11-fold) increased, contributing to antioxidant activity. In addition, the major ginsenosides of GBK were identified as Rg2 (10.1 μg/mg) and Re (6.59 μg/mg), and the content of minor ginsenosides, which are easily absorbed forms, increased 2.19-fold by fermentation. GBK also extended survival in a Drosophila model treated with 15% hydrogen peroxide. GBK also reduced reactive oxygen species (p < 0.001) through upregulation of gene expression of antioxidant enzymes such as catalase (p < 0.001), superoxide dismutase (p < 0.05), and glutathione peroxidase (p < 0.001). Therefore, GBK can be presented as a functional food that inhibits oxidative stress by increasing radical scavenging activity during fermentation.
Gender representation in leadership & research: A 13-year review of the Annual Canadian Society of Otolaryngology Meetings
Authors: Yi Grace , Payandeh Jennifer , Mavedatnia Dorsa , Neocleous Penelope , Davidson Jacob , Siu Jennifer , Zirkle Molly , Strychowsky Julie E. , Graham M. Elise , Chan Yvonne
Published: May 2023

Background

The gender disparity in surgical disciplines, specifically in speakers across North American medical and surgical specialty conferences, has been highlighted in recent literature. Improving gender diversity at society meetings and panels may provide many benefits. Our aim was to determine the state of gender diversity amongst presenters and speakers at the annual Canadian Society of Otolaryngology-Head and Neck Surgery (CSO) meetings.

Methods

Scientific programs for the CSO annual meetings from 2008 to 2020 were obtained from the national society website. Participant name, role, gender, location, and subspecialty topic were recorded for all roles other than poster presenter. Gender (male or female) was determined using an online search. The total number of opportunity spots and proportion of women was then calculated. Gender differences were analyzed using chi-square test and logistic regression with odds ratios. Four categories were analyzed: Society Leadership, Invited Speaker Opportunities, Workshop Composition (male-only panels or “manels”, female-only panels, or with at least one female speaker), and Oral Paper Presenters (first authors).

Results

There were 1874 leadership opportunity spots from 2008 to 2020, of which 18.6% were filled by women. Among elected leadership positions in the society, only 92 unique women filled 738 leadership opportunity spots. 13.2% of workshop chairs, 20.8% of panelists and 22.7% of paper session chairs were female. There was an overall increase in the proportion of leadership positions held by women, from 13.9% of leadership spots in 2008 to 30.1% in 2020. Of the 368 workshops, 61.1% were led by men only, 36.4% by at least 1 female surgeon, and 2.5% by women only. “Manels” have comprised at least 37.5% of workshops each year.

Conclusions

The proportion of women in speaking roles at the annual CSO meetings has generally increased over time, particularly among panelists, leading to fewer male-only speaking panels. However, there has been a slower rate of growth in the proportion of unique women in speaker roles. There remains an opportunity to increase gender/sex diversity at the major Canadian otolaryngology meeting.

Graphical Abstract
Could vertigo be a post-COVID-19 sequela or presenting symptom?
Authors: Daker Lamiaa I. , Elshafei Reham R. , Bahi Mohammad , Mohammed Asmaa , Erfan Randa , Gomaa Mohammed
Published: May 2023

Background

It has been postulated that COVID-19 has a substantial neuro-otological impact such as vertigo or dizziness that is rarely evaluated. The purpose of this research is to study the occurrence of vertigo (whether as presenting symptom or a sequela) and its etiological characteristics in patients with covid 19 infection and close contact. It is a cross-sectional study (convenient sample) conducted on patients that had a previous history of covid 19 infection and another group of contact individuals who presented with the sensation of vertigo. All the included participants underwent full neurological and otological examination, nasopharyngeal swab PCR to confirm COVID-19 infection and video nystgmograghy (VNG).

Results

it was included 44 participants, where 7 (15.9%) of the participants were post-COVID-19 patients and 37 (84.1%) were close contacts of COVID patients. It was found that 6(85.7%) of post-COVID-19 patients had vestibular neuritis (VN), and 1(14.3%) patient had Benign Paroxysmal Positional Vertigo (BPPV). 9(23%) of those in close contact had positive PCR for COVID infection, 6(66.7%) of them had VN, and the other 3 (33.3%) had BPPV.

Conclusion

Vertigo could be a possible complication or a presenting symptom in patients with COVID patients that is mainly attributed to peripheral vestibular dysfunction.
Interface design for residential energy feedback, in the Indian context
Authors: Garg Madhur , Garg Vishal , Srivastava Priyanka , Agarwal Rishika
Published: May 2023

Global access to electricity has increased from 78.2% to 2000 to 90.5% in 2020, resulting in an increased electricity demand worldwide. Unlike commercial electricity consumption, which is managed by professionals, residential consumption is managed by the householders, who often lack insight into their energy usage. Quality feedback, including detailed energy consumption and tips, can lead to substantial household savings. There are several mediums for providing energy feedback, such as Short Message Service (SMS), postal letter, email, mobile app, and In-Home Display (IHD). Studies suggest that feedback through electronic media can save up to 20% of energy consumption. In this work, we aim to design mobile application interfaces that can maximize energy savings through effective feedback. The level of savings realized is dependent on the user’s preferences and understanding of the information presented. User preferences are subjective of their profile (e.g., age, occupation, income) and the cultural context (e.g., country). The possibility of energy reduction is high when the provided information matches the user preferred information for feedback. Smart homes have recently been included as an annexure in India’s building energy code (Eco Niwas Samhita 2021), indicating a growing demand for quality energy feedback in India. However, there is a lack of research that addresses what feedback information is suitable for Indian users. We conducted two questionnaire-based surveys, one to understand users’ preferences for feedback information and another to validate the designed mobile application interface screens. The surveys were conducted on two age groups, young and middle-aged adults. A Chi-Square Test of Independence was performed to assess the relationship between the user’s preference for feedback information and their age group. Participants identified total energy consumption, appliance level disaggregated information, energy-saving tips, goals, and historical consumption comparisons as the top five information types. In contrast, normative comparison was the least preferred information. The follow-up design validations suggest that the interface should be customizable to accommodate the varying preferences of users. The current findings will help customize the energy feedback display UI design as per the Indian population.

Graphical Abstract
Full-waveform inversion by model extension: Practical applications
Authors: Barnier Guillaume , Biondi Ettore , Clapp Robert G. , Biondi Biondo
Published: May 2023

Producing reliable acoustic subsurface velocity models still remains the main bottleneck of the oil and gas industry’s traditional imaging sequence. In complex geologic settings, the output of conventional ray-based or wave-equation-based tomographic methods may not be sufficiently accurate for full-waveform inversion (FWI) to converge to a geologically satisfactory earth model. We create a new method referred to as full-waveform inversion by model extension (FWIME) in which a wave-equation migration velocity analysis (WEMVA) technique is efficiently paired with a modified version of FWI. We find that our method is more powerful than applying WEMVA and FWI sequentially, and that it can converge to accurate solutions without the use of a good initial guess or low-frequency energy. We determine FWIME’s potential on five realistic and challenging numerical examples that simulate complex geologic scenarios often encountered in hydrocarbon exploration. We guide the reader step by step throughout the optimization process. We find that our method can simultaneously invert all wave types with the same simple mechanism and without the need for a user-intensive hyperparameter tuning process. In an open-source online repository, we provide our C++/compute unified device architecture (CUDA) numerical implementation accelerated with graphics processing units, encapsulated in a Python interface. All the numerical examples developed are accessible through Python notebooks and fully reproducible.
Real-World First-Line Use of Pertuzumab With Different Taxanes for Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer: A Comparative Effectiveness Study Using US Electronic Health Records
Authors: Polito Letizia , Shim Jinjoo , Hurvitz Sara A. , Dang Chau T. , Knott Adam , Du Toit Yolande , Restuccia Eleonora , Sanglier Thibaut , Swain Sandra M.
Published: May 2023

PURPOSE

On the basis of the results from CLEOPATRA, pertuzumab plus trastuzumab and chemotherapy is the first-line standard of care for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). However, discrepancies have been reported between clinical trial and real-world outcomes. We report real-world outcomes for patients with HER2-positive MBC treated with first-line pertuzumab plus trastuzumab and a taxane in routine clinical practice in the United States.

METHODS

A retrospective analysis was conducted using electronic health record-derived deidentified data from the Flatiron Health database. Patients were grouped according to the first taxane received (paclitaxel/nab-paclitaxel or docetaxel). Median real-world progression-free survival (rwPFS) and overall survival (rwOS) was estimated using Kaplan-Meier methodology. Subgroup analyses were conducted in patients treated with docetaxel who met CLEOPATRA's key eligibility criteria.

RESULTS

We included 1,065 patients; 313 patients received paclitaxel/nab-paclitaxel and 752 received docetaxel. Patients who received paclitaxel/nab-paclitaxel were older, had a worse Eastern Cooperative Oncology Group Performance Status, and had more recurrent metastatic disease compared with the docetaxel group. After adjustment for potential confounders, similar median rwPFS (inverse probability of treatment weighted average treatment effect for the treated [IPTW-ATT] hazard ratio [HR], 1.09; 95% CI, 0.9 to 1.3; P = .365) and rwOS (IPTW-ATT HR, 1.23; 95% CI, 0.96 to 1.58; P = .101) was observed between treatment groups. In the subgroup of CLEOPATRA-eligible patients, median rwPFS and rwOS were 16.9 months and 57.8 months, respectively.

CONCLUSION

There was no statistically significant difference in real-world outcomes between patients treated with paclitaxel/nab-paclitaxel and those treated with docetaxel. Selecting patients using key CLEOPATRA eligibility criteria resulted in rwPFS and rwOS similar to those observed in CLEOPATRA, highlighting the importance of ensuring similar patient populations when comparing clinical trial and real-world data.
Genetic Prediction of Lifetime Risk of Fracture
Authors: Ho-Le Thao P , Tran Thach S , Nguyen Huy G , Center Jacqueline R , Eisman John A , Nguyen Tuan V
Published: May 2023

Context

Fragility fracture is a significant public health problem because it is associated with increased mortality. We want to find out whether the risk of fracture can be predicted from the time of birth.

Objective

To examine the association between a polygenic risk score (PRS) and lifetime fracture risk.

Methods

This population-based prospective study involved 3515 community-dwelling individuals aged 60+ years who have been followed for up to 20 years. Femoral neck bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry. A PRS was created by summing the weighted number of risk alleles for each single nucleotide polymorphism using BMD-associated coefficients. Fragility fractures were radiologically ascertained, whereas mortality was ascertained through a state registry. Residual lifetime risk of fracture (RLRF) was estimated by survival analysis.

Results

The mortality-adjusted RLRF for women and men was 36% (95% CI, 34%-39%) and 21% (18%-24%), respectively. Individuals with PRS > 4.24 (median) had a greater risk (1.2-fold in women and 1.1-fold in men) than the population average risk. For hip fracture, the average RLRF was 10% (95% CI, 8%-12%) for women and ∼5% (3%-7%) for men; however, the risk was significantly increased by 1.5-fold and 1.3-fold for women and men with high PRS, respectively.

Conclusion

A genetic profiling of BMD-associated genetic variants is associated with the residual lifetime risk of fracture, suggesting the potential for incorporating the polygenic risk score in personalized fracture risk assessment.
Unexpected Plasma Gonadal Steroid and Prolactin Levels Across the Mouse Estrous Cycle
Authors: Wall Ellen G , Desai Reena , Khant Aung Zin , Yeo Shel Hwa , Grattan David R , Handelsman David J , Herbison Allan E
Published: May 2023

Despite the importance of the mouse in biomedical research, the levels of circulating gonadal steroids across the estrous cycle are not established with any temporal precision. Using liquid chromatography–mass spectrometry, now considered the gold standard for steroid hormone analysis, we aimed to generate a detailed profile of gonadal steroid levels across the estrous cycle of C57BL/6J mice. For reference, luteinizing hormone (LH) and prolactin concentrations were measured in the same samples by sandwich enzyme-linked immunosorbent assay. Terminal blood samples were collected at 8-hour intervals (10 Am, 6 Pm, 2 Am) throughout the 4 stages of the estrous cycle. As expected, the LH surge was detected at 6 Pm on proestrus with a mean (±SEM) concentration of 11 ± 3 ng/mL and occurred coincident with the peak in progesterone levels (22 ± 4 ng/mL). Surprisingly, estradiol concentrations peaked at 10 Am on diestrus (51 ± 8 pg/mL), with levels on proestrus 6 Pm reaching only two-thirds of this value (31 ± 5 pg/mL). We also observed a proestrus peak in prolactin concentrations (132.5 ± 17 ng/mL) that occurred earlier than expected at 2 Am. Estrone and androstenedione levels were often close to the limit of detection (LOD) and showed no consistent changes across the estrous cycle. Testosterone levels were rarely above the LOD (0.01 ng/mL). These observations provide the first detailed assessment of fluctuating gonadal steroid and reproductive hormone levels across the mouse estrous cycle and indicate that species differences exist between mice and other spontaneously ovulating species.
Implementation of Nephroprotective Measures to Prevent Acute Kidney Injury in Septic Patients: A Retrospective Cohort Study
Authors: Sadjadi Mahan , Porschen Christian , von Groote Thilo , Albert Felix , Kellum John A. , Gomez Hernando , Meersch Melanie , Zarbock Alexander
Published: May 2023

BACKGROUND:

Sepsis remains the leading cause of mortality in critically ill patients, and mortality is increased when acute kidney injury (AKI) occurs. The Kidney Disease: Improving Global Outcomes (KDIGO) guideline recommends the implementation of supportive measures in patients at high risk for AKI. However, it remains unclear to what extent these nephroprotective measures are implemented in daily clinical practice in critically ill patients, especially those with high-risk exposures such as sepsis.

METHODS:

We analyzed the Medical Information Mart for Intensive Care IV (MIMIC-IV) database to identify septic patients with and without AKI. The primary outcome of interest was the adherence to the KDIGO bundle consisting of avoidance of nephrotoxic agents, implementation of a functional hemodynamic monitoring, optimization of perfusion pressure and volume status, close monitoring of renal function, avoidance of hyperglycemia, and avoidance of radiocontrast agents. Secondary outcomes included the development of AKI, progression of AKI, the use of renal replacement therapy (RRT), mortality, and a composite end point consisting of progression of AKI and mortality within 7 days.

RESULTS:

Our analysis included 34,679 patients with sepsis with 1.6% receiving the complete bundle (10% received 5, 42.3% 4, 35.4% 3, and 9.8% 2 bundle components). In 56.4%, nephrotoxic agents were avoided, and hemodynamic optimization was reached in 86.5%. Secondary end points were improved in patients with bundle adherence. Avoidance of nephrotoxic drugs and optimization of hemodynamics were significantly associated with lower rates of AKI and improved patient outcomes, including 30-day mortality.

CONCLUSIONS:

Implementation of the KDIGO bundle is poor in patients with sepsis but may be associated with improved outcomes.
Distinct hyperactive RAS/MAPK alleles converge on common GABAergic interneuron core programs
Authors: Knowles Sara J. , Stafford April M. , Zaman Tariq , Angara Kartik , Williams Michael R. , Newbern Jason M. , Vogt Daniel
Published: May 2023

RAS/MAPK gene dysfunction underlies various cancers and neurocognitive disorders. Although the roles of RAS/MAPK genes have been well studied in cancer, less is known about their function during neurodevelopment. There are many genes that work in concert to regulate RAS/MAPK signaling, suggesting that if common brain phenotypes could be discovered they could have a broad impact on the many other disorders caused by distinct RAS/MAPK genes. We assessed the cellular and molecular consequences of hyperactivating the RAS/MAPK pathway using two distinct genes in a cell type previously implicated in RAS/MAPK-mediated cognitive changes, cortical GABAergic interneurons. We uncovered some GABAergic core programs that are commonly altered in each of the mutants. Notably, hyperactive RAS/MAPK mutants bias developing cortical interneurons towards those that are somatostatin positive. The increase in somatostatin-positive interneurons could also be prevented by pharmacological inhibition of the core RAS/MAPK signaling pathway. Overall, these findings present new insights into how different RAS/MAPK mutations can converge on GABAergic interneurons, which may be important for other RAS/MAPK genes and related disorders.
Insights into the pathophysiology of DFNA44 hearing loss associated with CCDC50 frameshift variants
Authors: Lachgar-Ruiz María , Morín Matías , Martelletti Elisa , Ingham Neil J. , Preite Lorenzo , Lewis Morag A. , Serrão de Castro Luciana Santos , Steel Karen P. , Moreno-Pelayo Miguel Ángel
Published: May 2023

Non-syndromic sensorineural hearing loss (SNHL) is the most common sensory disorder, and it presents a high genetic heterogeneity. As part of our clinical genetic studies, we ascertained a previously unreported mutation in CCDC50 [c.828_858del, p.(Asp276Glufs*40)] segregating with hearing impairment in a Spanish family with SNHL associated with the autosomal dominant deafness locus DFNA44, which is predicted to disrupt protein function. To gain insight into the mechanism behind DFNA44 mutations, we analysed two Ccdc50 presumed loss-of-function mouse mutants, which showed normal hearing thresholds up to 6 months of age, indicating that haploinsufficiency is unlikely to be the pathogenic mechanism. We then carried out in vitro studies on a set of artificial mutants and on the p.(Asp276Glufs*40) and p.(Phe292Hisfs*37) human mutations, and determined that only the mutants containing the six-amino-acid sequence CLENGL as part of their aberrant protein tail showed an abnormal distribution consisting of perinuclear aggregates of the CCDC50 protein (also known as Ymer). Therefore, we conclude that the CLENGL sequence is necessary to form these aggregates. Taken together, the in vivo and in vitro results obtained in this study suggest that the two identified mutations in CCDC50 exert their effect through a dominant-negative or gain-of-function mechanism rather than by haploinsufficiency.
Direct sequencing of totalSaccharomyces cerevisiaetRNAs by LC–MS/MS
Authors: Jones Joshua D. , Simcox Kaley M. , Kennedy Robert T. , Koutmou Kristin S.
Published: May 2023

Among RNAs, transfer RNAs (tRNAs) contain the widest variety of abundant posttranscriptional chemical modifications. These modifications are crucial for tRNAs to participate in protein synthesis, promoting proper tRNA structure and aminoacylation, facilitating anticodon:codon recognition, and ensuring the reading frame maintenance of the ribosome. While tRNA modifications were long thought to be stoichiometric, it is becoming increasingly apparent that these modifications can change dynamically in response to the cellular environment. The ability to broadly characterize the fluctuating tRNA modification landscape will be essential for establishing the molecular level contributions of individual sites of tRNA modification. The locations of modifications within individual tRNA sequences can be mapped using liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS). In this approach, a single tRNA species is purified, treated with ribonucleases, and the resulting single-stranded RNA products are subject to LC–MS/MS analysis. The application of LC–MS/MS to study tRNAs is limited by the necessity of analyzing one tRNA at a time, because the digestion of total tRNA mixtures by commercially available ribonucleases produces many short digestion products unable to be uniquely mapped back to a single site within a tRNA. We overcame these limitations by taking advantage of the highly structured nature of tRNAs to prevent the full digestion by single-stranded RNA-specific ribonucleases. Folding total tRNA prior to digestion allowed us to sequenceSaccharomyces cerevisiaetRNAs with up to 97% sequence coverage for individual tRNA species by LC–MS/MS. This method presents a robust avenue for directly detecting the distribution of modifications in total tRNAs.
MODERN EDUCATIONAL TECHNOLOGIES IN TEACHING A FOREIGN LANGUAGE FOR LAWYERS
Authors: Mikhalyova Svetlana N.
Published: May 2023

In accordance with the Federal State Educational Standard of Higher Education, adopted by the order of the Ministry of Education and Science of the Russian Federation in February 2020, the implementation of various educational programs provides for the use of educational technologies. The article discusses the relevance of the search for modern technologies for teaching English to law students in the context of the implementation of the Federal State Educational Standard (3++). The author analyzes the possibilities of new pedagogical technologies and reveals their advantages. Based on the analysis of tasks for students, the author concluded that modern educational technologies contribute to the formation of foreign language competence in the process of teaching a professionally oriented foreign language course.

The article discusses modern educational technologies that are convenient to use when teaching a foreign language. Educational technologies include several convenient technological tools, an affordable, free, convenient service for work that can be used when preparing presentations, creating documents, various tables, as it offers a huge number of visual design options. The main results of the study are the scientific substantiation of the effectiveness of educational material.
VOLUNTEERING: ANALYSIS OF THE REGULATORY AND LEGISLATIVE FRAMEWORK
Authors: Shayakhmetova Rimma R.
Published: May 2023

Volunteering as a social phenomenon has been widely discussed by scientists and specialists over the past few years. International documents proclaim the equality of citizens’ rights to participate in volunteer activities, and also emphasize the need to strengthen the volunteer movement in all countries of the world. However, there are difficulties in a single comprehensive understanding of the phenomenon of “volunteering”. The article analyzes the activities of international organizations regulating volunteer work. The analysis of modern legislation after the adoption of amendments to the Constitution of the Russian Federation is carried out, and the possible consequences for the development of the social institution of “volunteering” in modern society are described.

Purpose. The aim of the study is to analyze the modern comprehensive understanding of the phenomenon of “volunteering”, the activities of international organizations in the development of volunteering and modern Russian legislation on volunteering.

Methodology. The main research method was the content analysis of Russian and foreign literature on volunteering and regulatory documents (official websites of the UN, UNDP, federal authorities). To achieve the goal of the study, the methodology of system analysis was used.

Results. The results of the work showed that volunteering is understood as a form of social service, carried out according to the free will of citizens, aimed at the disinterested provision of socially significant services at the local, national or international levels, contributing to personal growth and development of citizens (volunteers) performing this activity. The role of International Organizations is important in consolidating efforts in promoting volunteering. National governments and public institutions should work closely with voluntary organizations in setting common priorities for the development of the world. The state has recognized the importance of volunteering in its legal acts. Effective implementation of the socio-economic development of Russia is possible in partnership with civil institutions, including volunteers. Modern social challenges (pandemic COVID-19, fires, floods, etc.) reinforce and emphasize the importance of volunteering.

Practical implications. The results of the study can be applied in the field of social and youth policy.
Pedagogical foundations for the development of optimism in the future teacher: Monograph
Authors: Andreeva Yu.V.
Published: May 2023

This monograph explores conceptual approaches to the development of optimism as a professional and personal quality of future teachers, and also determines the conditions and technological foundations that affect its disclosure and development. As a leading favorable pedagogical condition, the situation of success created in the process of educational activity of the future teacher is presented. Within the framework of the favorable educational situation being created, real successes become a confirmation and a real justification for the pedagogical optimism of the teacher. A social-personal-active approach is proposed that takes into account the personal characteristics of each of the participants in the educational and pedagogical interaction. Addressed to a wide range of readers.
Don't let the spark be diminished: The value of CPD
Authors: Dooley Vanessa
Published: May 2023

Vanessa Dooley, director of Jigsaw Early Years Consultancy Ltd, discusses the importance of Continuing Professional Development to keep teams motivated and inspired, as well as easy ways to incorporate it into our busy professional lives.
We will keep fighting to reverse the ratio changes
Authors: Leitch Neil
Published: May 2023

Neil Leitch, chief executive of the Early Years Alliance outlines why the Alliance will continue to oppose the Government's increase to the minimum staff to child ratios from 1:4 to 1:5 for two-year-olds, announced in the March Spring Budget.
Imagining a Poetics of Loss
Authors: Al-Dahiyat Bayan , Majdoubeh Ahmad Y.
Published: May 2023

This article aims at showing how the poetry of Joy Harjo and Saadi Youssef becomes the imagined geography of the Muscogee (Creek) nation and Iraq respectively. Despite the different contexts of struggle, both poets depict a national community through imagining a decolonized geographical space where intellectuals and poetry act as witnesses to defy the colonial erasure of memory. This article will attempt to highlight certain intellectual and literary texts that take active part in imagining and presenting an anti-colonial counter discourse that would lead to a new understanding of national identity and nation. It will rely on Bill Ashcroft’s theory of Postcolonial Utopianism and building imagined homelands as well as Benedict Anderson’s concept of imagined communities. Representative poems from the two poets, Joy Harjo and Saadi Youssef, will be examined in order to shed light on the theoretical and imaginative creation of nations.
The Cutting Edge between Nationalistic Commitment (Iltizam) and Literary Compulsion (Ilzam) in Palestinian Literature
Authors: Tahboub Dima M. T.
Published: May 2023

This paper presents war literature as a distinctive genre intertwined with various schools of social thought and literary criticism including nationalism, social realism, and commitment. It puts forward a definition of war literature and the history of its emergence. It also attempts to explore some gray areas in war literature, relating to its artistic and creative modes of writing, its biases and prejudices. It questions the principles of authenticity and representation in this literary genre, addressing the contestation between reality and fiction, aesthetics and ideology, which dominate the discourse of postcolonial studies. The paper chooses Palestinian literature as a model case study, discussing the effects of the Sartrean school of commitment, Arabized in the concept ofAdab al-Iltizam, on the creativity and individuality of writers. It discusses some of the general characteristics and themes of Palestinian literature, moving from early war literature (1948) to more contemporary works (1990s-), and presents how some writers manage to walk the thin line between literary representation and national commitment and succeed, without falling into the quagmire of propaganda or mundanity, to depict a national cause still subjected to colonialism in a postcolonial era.
Polarization-based idler elimination: enhancing the efficiency of optical parametric amplification
Authors: Jansonas Gaudenis , Budriūnas Rimantas , Valiulis Gintaras , Varanavičius Arūnas
Published: May 2023

This study presents a novel way to increase the energy conversion efficiency of optical parametric amplification by eliminating the idler wave from the interaction using consecutive type-I and type-II amplification processes. By using the aforementioned straightforward approach the wavelength tunable narrow-bandwidth amplification with exceptionally high 40% peak pump-to-signal conversion efficiency and 68% peak pump depletion was achieved in the short-pulse regime, while preserving the beam quality factor of less than 1.4. The same optical layout can also serve as an enhanced idler amplification scheme.