bluuebunny/crossref_metadata_2025 huggingface dataset:
What is the role of aerosol transmission in SARS-Cov-2 Omicron spread in Shanghai?
Authors: Sun Gui-Quan , Ma Xia , Zhang Zhenzhen , Liu Quan-Hui , Li Bai-Lian
Published: November 2022

The Omicron transmission has infected nearly 600,000 people in Shanghai from March 26 to May 31, 2022. Combined with different control measures taken by the government in different periods, a dynamic model was constructed to investigate the impact of medical resources, shelter hospitals and aerosol transmission generated by clustered nucleic acid testing on the spread of Omicron. The parameters of the model were estimated by least square method and MCMC method, and the accuracy of the model was verified by the cumulative number of asymptomatic infected persons and confirmed cases in Shanghai from March 26 to May 31, 2022. The result of numerical simulation demonstrated that the aerosol transmission figured prominently in the transmission of Omicron in Shanghai from March 28 to April 30. Without aerosol transmission, the number of asymptomatic subjects and symptomatic cases would be reduced to 130,000 and 11,730 by May 31, respectively. Without the expansion of shelter hospitals in the second phase, the final size of asymptomatic subjects and symptomatic cases might reach 23.2 million and 4.88 million by May 31, respectively. Our results also revealed that expanded vaccination played a vital role in controlling the spread of Omicron. However, even if the vaccination rate were 100%, the transmission of Omicron should not be completely blocked. Therefore, other control measures should be taken to curb the spread of Omicron, such as widespread antiviral therapies, enhanced testing and strict tracking quarantine measures. This perspective could be utilized as a reference for the transmission and prevention of Omicron in other large cities with a population of 10 million like Shanghai.
Determinants of recommended antenatal care visits among pregnant women in Ethiopia: a generalized linear mixed-effects modeling
Authors: Ayalew Hiwotie Getaneh , Asefa Kibir Temesgen , Liyew Alemneh Mekuriaw
Published: November 2022

Background

Although antenatal care has the potential role to reduce maternal and child morbidity and mortality, utilization of a recommended number of antenatal care visits is still low in Ethiopia. Therefore, this study aimed to assess the determinants of recommended antenatal care visits in Ethiopia.

Method

Data from the 2019 mini-Ethiopian demographic and health survey (MEDHS) was used for this study. A total of 3916 women who gave birth 5 years preceding the MEDHS were included. A generalized linear mixed-effects (mixed-effects logistic regression) model was used to identify the determinants of recommended antenatal care service utilization. Finally, the adjusted odds ratio with a 95% confidence interval and random effects were reported.

Results

In the generalized linear mixed-effects model, women with primary education (AOR = 1.55, 95%CI 1.22–2.01), secondary and above education (AOR = 5.12, 95%CI 2.80–8.16), women from the middle (AOR = 1.25, 95%CI 1.01–1.71) and rich wealth index (AOR = 1.54, 95%CI 1.12–2.25), women who were exposed to media (AOR = 1.23,95%CI 1.01–1.57) and who use contraception (AOR = 1.45 95%CI 1.25–2.03), had higher odds of recommended antenatal care service utilization.

Conclusion

In this study, factors like maternal educational status, media exposure, wealth index and history of contraceptive utilization were significantly associated with recommended ANC visits in Ethiopia. Therefore, encouraging women for contraceptive service utilization, consulting women to be exposed to media and improving women’s wealth status will help to have recommended number of ANC visits by pregnant women in Ethiopia.
Attending pediatric acutely ill patients at home: families’ socioeconomic characterization, expectations, and experiences
Authors: Batlle Astrid , Thió-Henestrosa Santiago , Boada Imma , López Sandra , Moya Isabel , Fernández José Carlos , de Sevilla Mariona Fernández , García-García Juan José
Published: November 2022

Background

SJD a Casa is an acute pediatric hospital-at-home program that was initiated in 2019. For a thorough understanding of acute pediatric homecare programs, an analysis of all related factors, including the medical, social, and economic aspects as well as the family’s experience, is essential. However, no previous study has attempted a comprehensive evaluation of this topic in relation to a complex program such as ours (in terms of the diseases and treatments offered). In this study, we aimed to finely characterize the population that opts for pediatric homecare programs and obtain a thorough understanding of the families’ needs, which will improve our understanding of the program and potentially reveal possible deficiencies.

Methods

This prospective quantitative and qualitative study involved collection of ordinal data as well as statements made by the caregivers of patients undergoing homecare. A total of 372/532 families were asked to answer two independent questionnaires (preadmission and postadmission) that evaluated their socioeconomic characteristics; expectations and experiences; and factors influencing the preference for homecare. The results were presented as frequencies and comparisons (Fisher’s exact test).

Results

The families had an adequate social network and a less-than-expected workload, and most families responded that they would have repeated the experience despite the workload. The expectations regarding the caregiver’s well-being at home were better than the actual situation, since some caregivers experienced anxiety or fear. The rating for homecare was better than that for the inpatient care offered before the homecare transfer.

Conclusions

Families included in the program were content with the homecare program and mostly responded that they would repeat the experience if needed. Although the duration of the program was short-term, some caregivers may experience symptoms of burnout like anxiety, which should be taken into consideration. Despite its limitations, this study offers the possibility of improving our service portfolio by focusing on vulnerable families’ access to the program and the caregiver’s risk of burnout.
The efficacy and safety of intravesical chondroitin sulphate solution in recurrent urinary tract infections
Authors: Rahnama’i M. S. , Javan Balegh Marand A. , Röschmann-Doose K. , Steffens L. , Arendsen H. J.
Published: November 2022

Background

Urinary tract infections are among the most common indications for antibiotic therapy. The emergence of resistant uropathogens indicates the need for treatment alternatives. Replenishment of the glycosaminoglycan layer of the bladder, achieved by intravesical instillation of e.g. chondroitin sulphate (CS), is described to be a cornerstone in the therapy of cystitis. To retrospectively evaluate the efficacy of a therapy with 0.2% CS in patients suffering recurrent urinary tract infections (rUTI) in comparison to a treatment with low-dose long-term antibiotics (LDLTAB) and a combination of both.

Methods

A total of 151 patients with recurrent UTI who underwent intravesical therapy at Diaconesse hospital in Leiden, The Netherlands were included. 50 patients had been treated with CS, 51 patients had received LDLTAB, and 50 patients had received a combination therapy (LDLTABCS). Data recorded for baseline, after 6, and 12 months of treatment were evaluated. Descriptive statistics were calculated. Exploratory comparisons between groups and within groups were performed by using one-tailed and paired t-tests. Patients filled in a standardized quality of life questionnaire (EQ-5D).

Results

We found a statistically significant reduction of number of infections from 7.10 ± 0.50 SEM to 0.45 ± 0.07 SEM after 12 months therapy with CS compared to 12 months therapy with LDLTAB (from 7.04 ± 0.47 SEM to 1.8 ± 0.15 SEM). The number of visits to the urologist significantly decreased in the CS group from 7.46 ± 0.80 SEM to 1.28 ± 0.11 SEM and from 4.10 ± 0.29 SEM to 1.35 ± 0.11 SEM in the LDLTABCS group. In addition, a significant increase in Quality of life (QoL) was seen in the CS-group (from 58.2 ± 0.82 SEM to 80.43 ± 0.82 SEM) and in the LDLTABCS group (from 62.4 ± 0.97 SEM to 76.73 ± 1.06 SEM). There was no improvement in QoL with LDLTAB (from 58.24 ± 1.08 SEM to 58.96 ± 1.19 SEM). Evaluation’s evidence is limited due to its retrospective character.

Conclusions

Retrospective analysis of data from patients that underwent therapy for rUTIs confirms the safety and efficacy of CS and indicate a superiority to antibiotic treatment of rUTIs.
A personalized multi-interventional approach focusing on customized nutrition, progressive fitness, and lifestyle modification resulted in the reduction of HbA1c, fasting blood sugar and weight in type 2 diabetes: a retrospective study
Authors: Goyal Mehra Chhavi , Raymond Annie Mattilda , Prabhu Rekha
Published: November 2022

Background

Type 2 diabetes (T2D) is a chronic, progressive lifestyle disease and the most rapidly growing health challenge of the twenty-first century. The American Diabetes Association recommends that T2D reversal can be achieved through an organized, and systematic approach focusing on nutrition, fitness, and lifestyle management.

Aim

This study aimed to evaluate the effectiveness of a comprehensive and multi-interventional diabetes care program called Sugar. Fit Diabetes Reversal Programme (SDRP) on glycosylated haemoglobin (HbA1c), fasting blood sugar (FBS), and body weight for T2D reversal.

Methodology

SDRP is a personalized intervention study that uses technology-enabled medical management, dedicated coach-led diabetes, and nutrition experts. The study involved 150 patients living with type 2 diabetes in the age group of 20 to 80 years and having HbA1c of > 6.5%. In SDRP, the participants were assigned personal medical doctors specializing in diabetes, along with health coaches for providing customized nutrition, personalized fitness routines, relevant lifestyle modifications to holistically reverse type 2 diabetes. The HbA1c level, fasting blood sugar, and weight of the participants were measured at baseline and the end of the study (90th day). The effectiveness of SDRP was analyzed by comparing it with a control group that involved 110 individuals with type 2 diabetes managed by conventional pharmacotherapy and regular dietary advice but not participating in the SDRP.

Results

All 150 participants adhered to the program for 90 days. The analysis was performed on participants and represented as mean ± standard deviation (mean ± SD). At the end of SDRP, a significant reduction in HbA1c level, FBS, and weight was observed as compared to the control group. The results showed that Hba1c levels dropped from 9.0 ± 1.5% to 7.1 ± 1.3% with a mean change of 1.9 ± 1.5%; FBS levels decreased from 178.3 ± 57.1 mg/dL to 116.1 ± 24.2 mg/dL with a mean loss of 62.2 ± 51.8 mg/dL, and the weight decreased from 76.7 ± 12.7 kg to 73.8 ± 11.8 kg with a mean weight loss of 2.8 ± 1.6 kg. The results also showed that participants between 20 to 35 years showed the highest drop in HbA1c, FBS, and weight.

Conclusion

The findings indicate that a comprehensive and multi-interventional diabetes care program involving personalized nutrition, fitness, and lifestyle modification such as SDRP, help in significant and sustained improvements in HbA1c level, glycaemic control, and weight loss in adults with type 2 diabetes.
Unemployment and expenditure on health and education as mediators of the association between toothbrushing and global income inequalities
Authors: El Tantawi Maha , Aly Nourhan M. , Folayan Morenike Oluwatoyin
Published: November 2022

Objective

The study assessed the association of country-level income inequalities with the percentage of schoolchildren toothbrushing-at-least-twice-daily; and the mediating effect of country-level unemployment rate and governmental expenditure on health and education (EH&E).

Methods

This was an ecological study. The dependent variable was country-level toothbrushing-at-least-twice-daily among 11-15-year-old schoolchildren. Data for the period 2009 to 2019 were extracted from two global surveys about schoolchildren’s health and from manuscripts identified through a systematic search of three databases. The independent variable was country-level income inequalities measured by the Gini coefficient (GC) extracted from the Sustainable Development Report 2021. The mediators were the unemployment rate and EH&E. We stratified the sample by the level of GC and assessed the correlation between the dependent and independent variables in each stratum. Linear regression was used to assess the relations between the dependent and independent variables, and mediation path analysis was used to quantify the direct, indirect, and total effects.

Results

Data were available for 127 countries. The mean (SD) percentage of children who brushed-at-least-twice-daily was 67.3 (16.1), the mean (SD) GC = 41.4 (8.2), unemployment rate = 7.5 (4.7) and EH&E = 8.4 (3.3). The percentage of children brushing at-least-twice-daily had weak and non-significant correlation with GC that was positive in countries with the least inequality and negative for countries with higher levels of inequality. A greater percentage of schoolchildren brushing-at-least-twice-daily was significantly associated with higher GC (B = 0.76, 95%CI: 0.33, 1.18), greater EH&E (B = 1.67, 95%CI: 0.69, 2.64) and lower unemployment rate (B=-1.03, 95%CI: -1.71, -0.35). GC had a significant direct positive effect (B = 0.76, 95%CI: 0.33, 1.18), a significant indirect negative effect through unemployment and EH&E (B=-0.47, 95%CI: -0.79, -0.24) and a non-significant total positive effect (B = 0.29, 95%CI: -0.09, 0.67) on the percentage of schoolchildren brushing-at-least-twice-daily.

Conclusion

Unemployment and EH&E mediated the association between income inequality and toothbrushing. Country-level factors may indirectly impact toothbrushing.
Conteltinib (CT-707) in patients with advanced ALK-positive non-small cell lung cancer: a multicenter, open-label, first-in-human phase 1 study
Authors: Xing Puyuan , Zhao Qian , Zhang Li , Wang Hanping , Huang Dingzhi , Hu Pei , Sun Yinghui , Shi Yuankai
Published: November 2022

Background

Conteltinib (CT-707) is a potent second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) showing promising anti-tumor activities in preclinical studies. This study aimed to assess the safety, pharmacokinetic (PK), and efficacy of conteltinib in patients with ALK-positive non-small cell lung cancer (NSCLC).

Methods

In this multicenter, single-arm, open-label, first-in-human phase 1 study, conteltinib was taken orally at doses of 50 to 800 mg quaque die (QD) in a dose-escalation phase. If the response was observed in a dose cohort of the dose-escalation phase, dose expansion was started. The primary endpoints were maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and adverse events assessed by investigators.

Results

Between April 13, 2016, and February 8, 2020, 64 ALK-positive NSCLC patients were enrolled, including 41 (64.1%) patients with ALK TKI-naïve and 23 (35.9%) patients who received crizotinib previously. In the dose-escalation phase, 26 patients were treated with conteltinib at doses of 50 mg, 100 mg, 200 mg, 300 mg, 450 mg, 600 mg, and 800 mg QD. One DLT event was reported at the dose of 600 mg. MTD was not reached. Overall, 58 (90.6%) patients experienced treatment-related adverse events (TRAEs) and 9 (14.1%) patients had grade ≥ 3 TRAEs. The most common TRAEs were diarrhea (46 [71.9%]), serum creatinine elevated (29 [45.3%]), aspartate aminotransferase elevated (25 [39.1%]), and nausea (24 [37.5%]). Among 39 ALK TKI-naïve patients, the overall response rate (ORR) was 64.1% (25 of 39; 95% confidence interval [CI], 47.2–78.8), median progression-free survival (PFS) was 15.9 months (95% CI, 9.26–23.3), and median duration of response (DoR) was 15.0 months (95% CI, 9.06–25.8). Among 21 patients who received crizotinib previously, the ORR was 33.3% (7 of 21; 95% CI, 14.6–57.0), median PFS was 6.73 months (95% CI, 4.73–8.54), and median DoR was 6.60 months (95% CI, 3.77–13.3).

Conclusions

In this study, conteltinib showed manageable safety profile, favorable PK properties, and anti-tumor activity in advanced ALK-positive NSCLC patients. The recommended phase 2 dose was determined to be 600 mg QD for ALK TKI-naïve patients and 300 mg bis in die (BID) for patients who received crizotinib previously.

Trial registration

ClinicalTrials.gov, NCT02695550.
A signature based on five immune-related genes to predict the survival and immune characteristics of neuroblastoma
Authors: Ma KeXin , Zhang PeiPei , Xia Yu , Dong Lin , Li Ying , Liu Liu , Liu YaJuan , Wang YouJun
Published: November 2022

Background

MYCN amplification (MNA) has been proved to be related to poor prognosis in neuroblastoma (NBL), but the MYCN-related immune signatures and genes remain unclear.

Methods

Enrichment analysis was used to identify the significant enrichment pathways of differentially expressed immune-related genes (DEIRGs). Weight gene coexpression network analysis (WGCNA) was applied to reveal the correlation between these DEIRGs and MYCN status. Univariate and multivariate Cox analyses were used to construct risk model. The relevant fractions of immune cells were evaluated by CIBERSORT and single-sample gene set enrichment analysis (ssGSEA).

Results

Five genes, including CHGA, PTGER1, SHC3, PLXNC1, and TRIM55 were enrolled into the risk model. Kaplan–Meier survival analysis and receiver operating characteristic (ROC) curve showed that our model performed well in predicting the outcomes of NBL (3-years AUC = 0.720, 5-year AUC = 0.775, 10-years AUC = 0.782), which has been validated in the GSE49711 dataset and the E-MTAB-8248 dataset. By comparing with the tumor immune dysfunction and exclusion (TIDE) and tumor inflammation signature (TIS), we further proved that our model is reliable. Univariate and multivariate Cox regression analyses indicated that the risk score, age, and MYCN can serve as independent prognostic factors in the E-MATB-8248. Functional enrichment analysis showed the DEIRGs were enriched in leukocyte adhesion-related signaling pathways. Gene set enrichment analysis (GSEA) revealed the significantly enriched pathways of the five MYCN-related DEIRGs. The risk score was negatively correlated with the immune checkpoint CD274 (PD-L1) but no significant difference with the TMB. We also confirmed the prognostic value of our model in predicting immunotherapeutics.

Conclusion

We constructed and verified a signature based on DEIRG that related to MNA and predicted the survival of NBL based on relevant immune signatures. These findings could provide help for predicting prognosis and developing immunotherapy in NBL.
Biological activity of new bioactive steroids deriving from biotransformation of cortisone
Authors: Costa Stefania , Tedeschi Paola , Ferraro Luca , Beggiato Sarah , Grandini Alessandro , Manfredini Stefano , Buzzi Raissa , Sacchetti Gianni , Valacchi Giuseppe
Published: November 2022

Cortisone is a metabolite belonging to the corticosteroid class that is used pharmaceutically directly as a drug or prodrug. In addition to its large consumption, its use is linked to several side effects, so pharmaceutical research aims to develop effective drugs with low or no side effects, alternative compounds to cortisone are part of an active investment in ongoing research on drug discovery. Since biotransformation can be considered a source of new molecules with potential therapeutic use, the present work focuses on a preliminary in vitro study aimed at evaluating the mutagenic, anti-inflammatory, antioxidant and neuroprotective activity of SCA and SCB molecules obtained from the biotransformation of cortisone using Rh. Rhodnii strain DSM 43960. The results obtained are very encouraging due to the safety of biotransformed compounds with reference to genotoxicity checked by Ames test, to the very high antioxidant capacity and to the anti-inflammatory activity. In fact, thecompounds inhibited both the TNFα-stimulated expression and secretion of NFkB target cytokines, and COX activity, and can activate the glucocorticoid receptor. Finally SCA and SCB exhibited neuroprotective properties.
Neutrophil reverse migration
Authors: Xu Qichao , Zhao Wenqi , Yan Mingyang , Mei Hongxia
Published: November 2022

The behavior of neutrophils is very important for the resolution of inflammation and tissue repair. People have used advanced imaging techniques to observe the phenomenon of neutrophils leaving the injured or inflammatory site and migrating back into blood vessels in transgenic zebrafish and mice, which is called neutrophil reverse migration. Numerous studies have shown that neutrophil reverse migration is a double-edged sword. On the one hand, neutrophil reverse migration can promote the resolution of local inflammation by accelerating the clearance of neutrophils from local wounds. On the other hand, neutrophils re-enter the circulatory system may lead to the spread of systemic inflammation. Therefore, accurate regulation of neutrophil reverse migration is of great significance for the treatment of various neutrophil- mediated diseases. However, the mechanism of neutrophil reverse migration and its relationship with inflammation resolution is unknown. In this review, we reviewed the relevant knowledge of neutrophil reverse migration to elucidate the potential mechanisms and factors influencing reverse migration and its impact on inflammation in different disease processes.
Substance use, injection risk behaviors, and fentanyl-related overdose risk among a sample of PWID post-Hurricane Maria
Authors: Abadie Roberto , Cano Manuel , Habecker Patrick , Gelpí-Acosta Camila
Published: November 2022

Background

While natural disasters like hurricanes are increasingly common, their long-term effects on people who inject drugs are not well understood. Although brief in duration, natural disasters can radically transform risk environments, increasing substance use and drug-related harms.

Methods

Based on a study of people who inject drugs (PWID) and injection risk behaviors in rural Puerto Rico, the present study uses data from two different phases of the parent study. Data for 110 participants were collected from December 2015 to January 2017, soon before Hurricane Maria landed in September 2017; the 2019 phase, in the aftermath of the hurricane, included a total of 103 participants. The present study’s main analyses used data from 66 PWID who participated in both the pre-Maria and post-Maria interviews (66 individuals measured at two time points, for a total of 132 observations), using mixed-effects binomial logistic regression to examine recent overdose experiences pre- and post-Maria. A separate descriptive analysis included all 103 participants from the 2019 interview.

Results

After Hurricane Maria, some declines in injection frequency were observed (the percentage of people reporting injecting monthly or less increased from 3.0% before Hurricane Maria to 22.7% after Hurricane Maria). However, fewer PWID reported using a new needle for most or all injections. In the pre-Maria interview, 10.6% of participants indicated they had experienced an overdose during the year of the interview and/or the calendar year prior, and this figure increased to 24.2% in the post-Maria interview. In the regression analysis, the odds of reporting an overdose during the interview year and/or calendar year prior were three times as high post-Maria, relative to pre-Maria (odds ratio 3.25, 95% confidence interval 1.06–9.97).

Conclusion

Substance use patterns, injection risk behaviors, and overdose episodes and deaths differed after Hurricane Maria, relative to before the hurricane, yet it is unclear to what extent these changes also reflect the simultaneous arrival of fentanyl. In preparation for future natural disasters, it is imperative to strengthen the health infrastructure by enhancing access and curbing barriers to syringe services programs and medications for opioid use disorder, particularly in rural or underserved locations.
Developing guiding principles for technology-based rehabilitation program by engaging people with motor incomplete tetraplegia
Authors: Bell Alison , Grampurohit Namrata , Kains Gabrielle , Marino Ralph J.
Published: November 2022

Background

Technology-aided rehabilitation is well established in the field of neurologic rehabilitation. Despite the widespread availability, the development of technology-based interventions that incorporate perspectives of the people who will use them is lacking.

Objectives

This qualitative study aims to understand how people with chronic motor incomplete cervical spinal cord injury view rehabilitation technology to improve upper extremity function and neuromuscular recovery to inform future intervention development.

Methods

Seven participants with chronic upper extremity impairment due to spinal cord injury/dysfunction trialed five rehabilitation technology devices. After a 30–45 min trial for each device, participants engaged in a semi-structured interview. Interviews were analyzed using a qualitative approach to explore the experience using and understand features that support motivation to use of rehabilitation technology.

Results

Qualitative analysis revealed three major themes: (1) devices must be flexible to meet diverse needs; (2) intervention protocols must be individualized to address unique needs and contexts of users; (3) intervention protocols should be developed and updated by a skilled clinician. These themes and subthemes were used to describe guiding principles to inform future intervention design.

Conclusion

The experiences of people with cervical spinal cord injury can be elicited as part of the intervention design process to systematically develop protocols for future feasibility trials. The findings from this study can be used to inform the development of technology-aided rehabilitation programs to improve upper extremity function in people with chronic motor incomplete tetraplegia.

Clinical trials registration number: NCT04000256
Time trends in emotional well-being and self-esteem in children and adolescents during the COVID-19 pandemic
Authors: Goto Ryunosuke , Piedvache Aurelie , Hangai Mayumi , Yamaoka Yui , Sampei Mariko , Sawada Naomi , Okubo Yusuke , Tanaka Kyoko , Morisaki Naho , Hosozawa Mariko
Published: November 2022

Objective

Given their unique COVID-19 pandemic experience, it is necessary to evaluate the mental health of youth beyond the initial stages of the pandemic, in relation to the stringency of the social distancing measures. We aimed to describe long-term trends in emotional well-being and self-esteem among youth in Japan during the pandemic.

Method

Using serial cross-sectional data from April 2020 to December 2021, we evaluated the trends in emotional well-being and self-esteem of youth aged 6–17 years using the self-report KINDL questionnaire, weighted to represent the age and gender distributions in the Japanese population. We then tested the associations between emotional well-being and self-esteem and stringency of social distancing policies, measured using the Oxford COVID-19 Stringency Index. Analyses were also stratified by gender and age group.

Results

The emotional well-being and self-esteem of youth improved transiently in 2020, followed by a slight worsening trend into 2021. While emotional well-being stayed lower compared to initial levels nearly 2 years into the pandemic, self-esteem began to improve by late 2021. 12–17 year-olds had lower emotional well-being and self-esteem compared to 6–11 year-olds throughout the study period. Females had lower emotional well-being than males in May 2020 and lower self-esteem than males in May and September/October 2020. More stringent social distancing measures were associated with lower emotional well-being and self-esteem, especially 6–11 year-olds’ self-esteem and females’ emotional well-being.

Conclusion

During the COVID-19 pandemic, older youth tended to have lower emotional well-being and self-esteem than younger youth. Younger and female youth were especially vulnerable to stringent social distancing measures.
UBR7 inhibits HCC tumorigenesis by targeting Keap1/Nrf2/Bach1/HK2 and glycolysis
Authors: Zhao Liang , Kang Min , Liu Xiaomeng , Wang Zhenran , Wang Yan , Chen Haiqiang , Liu Wenhui , Liu Shiqian , Li Baibei , Li Chong , Chang Antao , Tang Bo
Published: November 2022

Background

Glycolysis metabolism is an attractive target for cancer therapy. Reprogramming metabolic pathways could improve the ability of metabolic inhibitors to suppress cancers with limited treatment options. The ubiquitin–proteasome system facilitates the turnover of most intracellular proteins with E3 ligase conferring the target selection and specificity. Ubiquitin protein ligase E3 component N-recognin 7 (UBR7), among the least studied E3 ligases, recognizes its substrate through a plant homeodomain (PHD) finger. Here, we bring into focus on its suppressive role in glycolysis and HCC tumorigenesis, dependent on its E3 ubiquitin ligase activity toward monoubiquitination of histone H2B at lysine 120 (H2BK120ub).

Methods

In this study, we carried out high-throughput RNAi screening to identify epigenetic candidates in regulating lactic acid and investigated its possible roles in HCC progression.

Results

UBR7 loss promotes HCC tumorigenesis both in vitro and in vivo. UBR7 inhibits glycolysis by indirectly suppressing HK2 expression, a downstream target of Nrf2/Bach1 axis. Mechanically, UBR7 regulates H2BK120ub to bind to Keap1 promoter through H2BK120ub monoubiquitination, thereby modulating Keap1 expression and downstream Nrf2/Bach1/HK2 signaling. Pharmaceutical and genetic inhibition of glycolytic enzymes attenuate the promoting effect of UBR7 deficiency on tumor growth. In addition, methyltransferase ALKBH5, downregulated in HCC, regulated UBR7 expression in an m6A-dependent manner.

Conclusions

These results collectively establish UBR7 as a critical negative regulator of aerobic glycolysis and HCC tumorigenesis through regulation of the Keap1/Nrf2/Bach1/HK2 axis, providing a potential clinical and therapeutic target for the HCC treatment.
Autologous hematopoietic stem cell transplantation improves long-term survival—data from a national registry
Authors: Blank Norbert , Schmalzing Marc , Moinzadeh Pia , Oberste Max , Siegert Elise , Müller-Ladner Ulf , Riemekasten Gabriela , Günther Claudia , Kötter Ina , Zeidler Gabriele , Pfeiffer Christiane , Juche Aaron , Jandova Ilona , Ehrchen Jan , Susok Laura , Schmeiser Tim , Sunderkötter Cord , Distler Jörg H. W. , Worm Margitta , Kreuter Alexander , Keyßer Gernot , Lorenz Hanns-Martin , Krieg Thomas , Hunzelmann Nicolas , Henes Jörg ,   on behalf of the German Network for Systemic Sclerosis
Published: November 2022

Background

Current recommendations on the management of systemic sclerosis (SSc) suggest that autologous hematopoietic stem cell therapy (HSCT) can be a rescue therapy for patients with rapidly progressive SSc.

Objectives

To assess the safety and efficacy of HSCT for patients with SSc and to compare these with non-HSCT patients in a control cohort with adjusted risk factors.

Methods

A retrospective analysis of data from the multicentric German network for systemic scleroderma (DNSS) with 5000 patients with SSc. Control groups consisted of all patients with diffuse cutaneous (dc)-SSc (group A) and an adjusted high-risk cohort of male patients with Scl70-positive dc-SSc (group B).

Results

Eighty SSc patients received an HSCT 4.1 ± 4.8 years after SSc diagnosis. Among them, 86.3% had dc-SSc, 43.5% were males, and 71.3% were positive for Scl70 antibodies. The control group A (n=1513) showed a significant underrepresentation of these risk factors for mortality. When the survival of the control group B (n=240) was compared with the HSCT group, a lower mortality of the latter was observed instead. Within 5 years after HSCT, we observed an improvement of the mRSS from 17.6 ± 11.5 to 11.0 ± 8.5 (p=0.001) and a stabilization of the DLCO. We did not see differences in transplant-related mortality between patients who received HSCT within 3 years after SSc diagnosis or later.

Conclusion

Our analysis of real-life data show that the distribution of risk factors for mortality is critical when HSCT cohorts are compared with non-HSCT control groups.
Diabetes management behaviors associated with depression in the U.S.
Authors: Lai Tim C. , McDaniel Cassidi C. , Chou Chiahung
Published: November 2022

Background

There is a lack of nationally representative evidence from the U.S. investigating the relationships between depression and diabetes management behaviors. Our study aimed to assess the associations between diabetes management behaviors and depression status, and to compare U.S. population-level percentages of diabetes management behaviors among patients with and without depression.

Methods

A cross-sectional study was conducted using population-based survey data to assess patient-reported variables retrospectively. We used the Behavioral Risk Factor Surveillance System (BRFSS) data and included states in the U.S. that continuously adopted the diabetes optional modules in 2013, 2015, 2017, and 2019. We included U.S. adults (≥ 18 years old) with self-reported diabetes in our analysis. Main outcomes were diabetes management behaviors (i.e., self-check for blood glucose and feet sores/irritation, regular diabetes clinical visit, HbA1c check, professional feet check, and dilated eye examination) and lifestyle behaviors (i.e., exercise, smoking, and alcohol consumption).

Results

Among the 74,011 respondents with diabetes, patients with depression had a higher likelihood of performing routine HbA1c checks (adjusted odds ratio (AOR) = 1.12; 95% CI 1.01–1.23) but had a lower likelihood to perform regular self-check for blood glucose (AOR = 0.91; 95% CI 0.84–0.99), receive professional feet checks (AOR = 0.87; 95% CI 0.79–0.95), and receive a dilated eye examination (AOR = 0.89; 95% CI 0.82–0.98). For lifestyle behaviors, patients with depression were more likely to smoke (No smoking (AOR) = 0.65; 95% CI = 0.59–0.72) and less likely to engage in sufficient exercise time (AOR = 0.69; 95% CI 0.63–0.75). There were no significant associations between depression and other behaviors, including self-check for feet sores/irritation (AOR = 0.99; 95% CI 0.92–1.08), regular diabetes clinical visit (AOR = 1.03, 95% CI 0.94–1.13), and alcohol consumption (AOR = 1.01, 95% CI 0.92–1.10).

Conclusions

The association between depression status and diabetes management behaviors varied. People with depression were positively associated with HbA1c checks. However, less uptake of other behaviors may indicate the needs for improvement in diabetes management.
Efficacy of resistive exercise on skeletal muscle-related outcomes in cancer survivors: a systematic review protocol
Authors: Dawson Jacqueline K. , Kang Dong-Woo , Barnes Oscar , Wilson Rebekah L. , Norris Mary K. , Dieli-Conwright Christina M.
Published: November 2022

Background

Symptom burden and adverse treatment effects can negatively impact physical function, health-related outcomes, and quality of life in cancer survivors. Resistive exercise that improves skeletal muscle function can ameliorate these complications, but the central role of the skeletal muscle in mediating improvements in patient-related outcomes has not been explored. This protocol describes the rationale and methods for a systematic review that aims to determine the effects of resistive exercise on the skeletal muscle hypertrophy, muscle performance, and muscle-related biomarkers in cancer survivors.

Methods

A systematic review will be conducted on peer-reviewed randomized controlled trials (RCTs) that employ resistive exercise interventions for cancer survivors. The following electronic databases will be searched: AMED, CENTRAL, CINAHL, CIRRIE, EMBASE, MEDLINE, PEDro, REHABDATA, Scopus, and SPORTDiscus. Studies will be considered for inclusion if they present quantitative data in adult cancer survivors on skeletal muscle characteristics (e.g., muscle mass), muscle performance (e.g., strength), or skeletal muscle-related biomarkers (e.g., myocellular satellite cells). Secondary outcomes will be physical function (e.g., stair climb) and patient-reported outcomes (e.g., fatigue). Data will be reported through a narrative that describes study design, participants, interventions, and outcome characteristics.

Discussion

This systematic review will help clarify the influence of resistive exercise on factors relating to the skeletal muscle in adult cancer survivors. Findings may provide insight into optimal exercise selection for evidence-based practice.

Systematic review registration

PROSPERO: #277791 [under review]
Determinants of the sustainability and growth of micro and small enterprises (MSEs) in Ethiopia: literature review
Authors: Teka Beza Muche
Published: November 2022

The role of micro and small enterprises (MSEs) has been recognized in Ethiopia at the strategic and policy levels. They are considered as a way to create jobs, alleviate poverty, ensure food security, and promote private sector development. Despite several government programs and support schemes aimed at empowering MSEs to be more competitive and sustainable, they continue to fail at alarming rates. Previous studies revealed that the failure rate of MSEs in developing countries like Ethiopia is higher than in developed countries due to a variety of internal and external factors. Thus, the objective of this study was to identify the major factors that commonly affect the sustainability and growth of MSEs in Ethiopia through systematic literature review. In order to achieve the objective of the study; published previous research works (journal articles) in the manufacturing and service sector from 2006 to 2021 were used. The findings from different empirical studies revealed that financial factors, marketing factors, political-legal variables, lack of adequate infrastructure, technological factors and manager or owner personal characteristics are the major factors that commonly determine the sustainability and growth of MSEs in Ethiopia. Finally, the study suggested that government, non-governmental organizations (NGOs), and financial institutions should give great attention towards the sustainability and growth of MSEs in Ethiopia.
Quantifying the employment impacts of gross exports: a global accounting perspective
Authors: Llop Maria
Published: November 2022

This article presents a method for quantifying the (domestic) employment consequences directly attributed to gross exports by taking into account the complex and global nature of production chains. Using a multi-country input–output (IO) structure of world production, the method derives measurements for the number of jobs and amount of labour income supported by a country’s export-related production. By quantifying how much domestic employment is determined by a country’s export activity, it offers a complementary (labour-focused) view on the more common (value-added focused) analyses for evaluating the economic impact of trade. This approach highlights the importance of exports in creating jobs and labour income, especially in the European Union and China. In contrast, gross exports in the United States show a (comparatively) weak influence in supporting US employment.
Reinforcement learning method for machining deformation control based on meta-invariant feature space
Authors: Zhao Yujie , Liu Changqing , Zhao Zhiwei , Tang Kai , He Dong
Published: November 2022

Precise control of machining deformation is crucial for improving the manufacturing quality of structural aerospace components. In the machining process, different batches of blanks have different residual stress distributions, which pose a significant challenge to machining deformation control. In this study, a reinforcement learning method for machining deformation control based on a meta-invariant feature space was developed. The proposed method uses a reinforcement-learning model to dynamically control the machining process by monitoring the deformation force. Moreover, combined with a meta-invariant feature space, the proposed method learns the internal relationship of the deformation control approaches under different stress distributions to achieve the machining deformation control of different batches of blanks. Finally, the experimental results show that the proposed method achieves better deformation control than the two existing benchmarking methods.
Development of therapeutic antibodies for the treatment of diseases
Authors: Wang Zeng , Wang Guoqing , Lu Huaqing , Li Hongjian , Tang Mei , Tong Aiping
Published: November 2022

Since the first monoclonal antibody drug, muromonab-CD3, was approved for marketing in 1986, 165 antibody drugs have been approved or are under regulatory review worldwide. With the approval of new drugs for treating a wide range of diseases, including cancer and autoimmune and metabolic disorders, the therapeutic antibody drug market has experienced explosive growth. Monoclonal antibodies have been sought after by many biopharmaceutical companies and scientific research institutes due to their high specificity, strong targeting abilities, low toxicity, side effects, and high development success rate. The related industries and markets are growing rapidly, and therapeutic antibodies are one of the most important research and development areas in the field of biology and medicine. In recent years, great progress has been made in the key technologies and theoretical innovations provided by therapeutic antibodies, including antibody–drug conjugates, antibody-conjugated nuclides, bispecific antibodies, nanobodies, and other antibody analogs. Additionally, therapeutic antibodies can be combined with technologies used in other fields to create new cross-fields, such as chimeric antigen receptor T cells (CAR-T), CAR-natural killer cells (CAR-NK), and other cell therapy. This review summarizes the latest approved or in regulatory review therapeutic antibodies that have been approved or that are under regulatory review worldwide, as well as clinical research on these approaches and their development, and outlines antibody discovery strategies that have emerged during the development of therapeutic antibodies, such as hybridoma technology, phage display, preparation of fully human antibody from transgenic mice, single B-cell antibody technology, and artificial intelligence-assisted antibody discovery.
Διαγενεακή μεταφορά αυτοεκτίμησης στην εφηβεία: ο ρυθμιστικός ρόλος του φύλου και της σειράς γέννησης και ο διαμεσολαβητικός ρόλος της γονικότητας
Authors: Μαστέλλου Ειρήνη-Σπυριδούλα , Τάνταρος Σπυρίδων
Published: November 2022

Υπάρχει σημαντικός αριθμός ερευνών για την επίδραση της γονικής συμπεριφοράς στην αυτοεκτίμηση των εφήβων· ωστόσο, η Διαγενεακή Μεταφορά της αυτοεκτίμησης παραμένει ακόμη ένα ανοικτό πεδίο έρευνας. Η παρούσα μελέτη επικεντρώνεται στη μελέτη της Διαγενεακής Μεταφοράς της αυτοεκτίμησης από τη μητέρα στο εφηβικής ηλικίας τέκνο της, με πιθανούς ρυθμιστικούς παράγοντες το φύλο και τη σειρά γέννησης του εφήβου καθώς και διαμεσολαβητικούς παράγοντες τη γονικότητα της μητέρας και τον τρόπο που την αντιλαμβάνεται ο έφηβος. Συμμετείχαν 201 δυάδες μητέρων-εφήβων ηλικίας 14 ετών, οι οποίοι συμπλήρωσαν μέσω ηλεκτρονικών φορμών την «Κλίμακα Αυτοεκτίμησης του Rosenberg», το «Ερωτηματολόγιο Γονικής Συμπεριφοράς» και την «Κλίμακα Συναισθηματικής Σύνδεσης». Όσον αφορά την αυτοεκτίμηση, τα αποτελέσματα έδειξαν ηλικιακές και διαφυλικές διαφορές, όπως και διαφορές σχετικά με τη σειρά γέννησης, καθώς και σημαντική αλληλεπίδραση μεταξύ τους. Η αυτοεκτίμηση της μητέρας φάνηκε να επιδρά σημαντικά στην αυτοεκτίμηση του εφήβου, επιβεβαιώνοντας την υπόθεση της Διαγενεακής Μεταφοράς. Ο ρυθμιστικός ρόλος του φύλου, καθώς και η αλληλεπίδραση του φύλου με τη σειρά γέννησης έδειξε ισχυρότερη επίδραση ανάμεσα στην αυτοεκτίμηση μητέρας-κόρης, ιδίως της πρωτότοκης. Επιπλέον, επιβεβαιώθηκε ο διαμεσολαβητικός ρόλος της γονικότητας όπως την αντιλαμβάνεται ο έφηβος, αλλά όχι η μητέρα, εξηγώντας μερικώς τη Διαγενεακή Μεταφορά της αυτοεκτίμησης.
Ατομική και οικογενειακή ανθεκτικότητα: ο ρόλος της γονικότητας
Authors: Μιχαηλίδου Μαρίνα , Γεωργίου Στέλιος Ν.
Published: November 2022

Σκοπός της παρούσας θεωρητικής περιγραφής είναι να σκιαγραφηθεί το φαινόμενο της ανθεκτικότητας ως ένα συστημικό και πολυδιάστατο φαινόμενο που μπορεί να θωρακίσει τα παιδιά και τις οικογένειες απέναντι σε παράγοντες επικινδυνότητας που αυξάνουν την πιθανότητα δημιουργίας προβλημάτων στην ανάπτυξη του παιδιού και της οικογένειας. Επιπρόσθετα, συζητείται ο  ρόλος που διαδραματίζει η γονικότητα στη διαμόρφωση της ατομικής ανθεκτικότητας του παιδιού και της ανθεκτικότητας του οικογενειακού συστήματος, αλλά και ο πιθανός συνδετικός ρόλος της γονικότητας ανάμεσα στην ανθεκτικότητα των δυο συστημάτων (ατομικού και οικογενειακού). Τέλος, γίνονται εισηγήσεις για περαιτέρω διερεύνηση σε θέματα που θα οδηγήσουν στην κατανόηση του τρόπου με τον οποίο η γονικότητα προσδιορίζει την ανθεκτικότητα των δυο συστημάτων.
Identification of highly specific antibodies for Serine/threonine-protein kinase TBK1 for use in immunoblot, immunoprecipitation and immunofluorescence
Authors: Alshafie Walaa , Fotouhi Maryam , Shlaifer Irina , Ayoubi Riham , Edwards Aled M. , Durcan Thomas M. , McPherson Peter S. , Laflamme Carl
Published: November 2022

TBK1 is a serine-threonine protein kinase that has been linked to a number of diseases including amyotrophic lateral sclerosis and frontotemporal dementia. Reproducible research on TBK1 has been hampered by the lack of well characterized antibodies. In this study, we characterized 11 commercial antibodies for TBK1 for use in immunoblot, immunofluorescence and immunoprecipitation, using an isogeneic knock-out cell line as a control. We identify antibodies that appear specific for all three applications but invite the readers to interpret the present findings based on their own scientific expertise and use this report as a guide to select the most appropriate antibody for their specific needs.
On the Complexity of Configuration and Orchestration for Enabling Disaggregated Server Provisioning in Optical Composable Data Centres
Authors: Pagès Albert , Agraz Fernando , Spadaro Salvatore
Published: November 2022

Due to the limitations of traditional data center (DC) architectures, the concept of infrastructure disaggregation has been proposed. DC resources are separated into multiple blades to be exploited independently. As a result, composable DC (CDC) infrastructures are achieved, enhancing the modularity of resource provisioning. However, disaggregation introduces additional challenges that need to be carefully analyzed. One relates to the potential complexity increase on the orchestration and infrastructure configuration that need to be performed when provisioning resources to support services. This aspect is highly influenced by the distribution of resources at the physical infrastructure. As such, when analyzing the performance of a CDC, it becomes essential to also study the related operational complexity of the resource orchestration and configuration phases. Furthermore, the requirements of several tenant services may impose heterogeneous deployments over the shared physical infrastructure in the form of either disaggregated single-server or multi-server distributions. The associated orchestration/configuration cost is again highly influenced by the data plane architecture of the CDC. With these aspects in mind, in this paper, we provide a methodology for analysis of the complexity of resource orchestration for a service deployment and the associated configuration cost in optical CDCs, considering various service deployment setups. A selected set of CDC architectures found in the literature is employed to quantitatively illustrate how the data plane design and service deployment strategies affect the complexity of infrastructure configuration and resource orchestration.