bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and change in social inequalities in physical activity before and during the COVID-19 pandemic in Sweden
Authors: Brattlöf Frida , Gustafsson Per E. , San Sebastián Miguel
Published: January 2023

Background

Physical activity is crucial for our wellbeing. Since the COVID-19 pandemic emerged, physical activity behaviour has changed globally, and social inequalities that already exist in physical activity have increased. However, there is limited knowledge of how these inequalities have evolved in Sweden. Thus, the aim of this study was to assess the prevalence of physical activity, and the socioeconomic inequalities in physical activity before and during the COVID-19 pandemic.

Methods

This study analysed data from the national ‘Health on Equal Terms’ survey which was conducted on participants between 16 and 84, through a repeated cross-sectional design in 2018 (pre-pandemic) and 2021 (during the pandemic). The socioeconomic variables included gender, age, education, occupation, income, and place of birth. For both years, the prevalence of low physical activity, the absolute risk differences, the slope index of inequality, and the slope index difference for each of the variables were calculated.

Results

The level of physical activity increased for the total population studied. However, the social inequalities that existed in 2018 increased over time and across age, education, occupation, income, and place of birth, but not with regard to gender.

Conclusions

Even though the Swedish population increased their levels of physical activity during the COVID-19 pandemic, the social inequalities that already existed in physical activity increased. Interventions to increase the level of physical activity among the young, people with low socioeconomic status, and those born outside Sweden are needed to reduce these social inequalities, and to improve the Swedish population’s wellbeing.
Postoperative complications and short-term prognosis of laparoscopic pancreaticoduodenectomy vs. open pancreaticoduodenectomy for treating pancreatic ductal adenocarcinoma: a retrospective cohort study
Authors: Zhang Bin , Xu Zipeng , Gu Weifang , Zhou Junjing , Tang Neng , Zhang Shuo , Chen Chaobo , Zhang Zhongjun
Published: January 2023

Background

Although laparoscopic pancreaticoduodenectomy (LPD) has been accepted worldwide for treating pancreatic ductal adenocarcinoma (PDA), it is a very technical and challenging procedure. Also, it is unclear whether LPD is superior to open pancreaticoduodenectomy (OPD). This study summarized the experience and efficacy of LPD for treating PDA in our medical center.

Methods

This retrospective cohort study included patients with PDA admitted at the Affiliated Hospital of Jiangnan University from October 2019 and January 2021. Patients received either LPD or OPD. Clinical outcomes (operation time, duration of anesthesia, intraoperative hemorrhage), postoperative complications, and short-term outcomes were compared. Cox proportional hazard model and Kaplan-Meier method were used to analyze overall survival (OS) and progression-free survival (PFS).

Results

Among the PDA patients, 101 patients underwent surgical treatment, 4 patients converted from LPD to OPD, and 7 of them received conservative treatment. Forty-six patients were cured of LPD, and 1 of them died shortly after the operation. Moreover, 44 patients received OPD, and there were 2 postoperative deaths. There were significant differences in the location of the operation time, duration of anesthesia, postoperative hemorrhage, abdominal infections, and postoperative pneumonia between the two groups (all p < 0.05). Multivariate analysis showed that LPD was an independent factor negatively correlated with the incidence of pneumonia (relative risk (RR) = 0.072, 95%CI: 0.016–0.326, p = 0.001) and abdominal infection (RR = 0.182, 95%CI: 0.047–0.709, p = 0.014). Also, there were no differences in OS (hazard ratio (HR) = 1.46, 95%CI: 0.60–3.53, p = 0.40) and PFS (HR = 1.46, 95%CI: 0.64–3.32, p = 0.37) at 12 months between the two groups.

Conclusions

LPD could be efficacy and feasible for managing selected PDA patients. Also, LPD has a better effect in reducing postoperative pneumonia and abdominal infection compared to OPD.
The dual role of microRNA (miR)-20b in cancers: Friend or foe?
Authors: İlhan Ahmet , Golestani Shayan , Shafagh Seyyed Ghavam , Asadi Fatemeh , Daneshdoust Danyal , Al-Naqeeb Bashar Zuhair Talib , Nemati Mohammed Mahdi , Khalatbari Fateme , Yaseri Amirhossein Fakhre
Published: January 2023

MicroRNAs, as non-coding transcripts, modulate gene expression through RNA silencing under normal physiological conditions. Their aberrant expression has strongly associated with tumorigenesis and cancer development. MiR-20b is one of the crucial miRNAs that regulate essential biological processes such as cell proliferation, apoptosis, autophagy, and migration. Deregulated levels of miR-20b contribute to the early- and advanced stages of cancer. On the other hand, investigations emphasize the tumor suppressor ability of miR-20b. High-throughput strategies are developed to identify miR-20b potential targets, providing the proper insight into its molecular mechanism of action. Moreover, accumulated results suggest that miR-20b exerts its effects through diverse signaling pathways, including PI3K/AKT/mTOR and ERK axes. Restoration of the altered expression levels of miR-20b induces cell apoptosis and reduces invasion and migration. Further, miR-20b can be used as a biomarker in cancer. The current comprehensive review could lead to a better understanding of the miR-20b in either tumorigenesis or tumor regression that may open new avenues for cancer treatment.
Leveraging a cuproptosis-based signature to predict the prognosis and drug sensitivity of cutaneous melanoma
Authors: Liu Da , Yang Fan , Zhang Tongtong , Mao Rui
Published: January 2023

Immunotherapy is a vital treatment for patients with cutaneous melanoma (CM), but effective predictors to guide clinical immunotherapy are lacking. Cuproptosis is a newly discovered mode of cell death related to tumorigenesis. Exploring the relationship between the mode of cuproptosis and the effect of immunotherapy on CM could better guide clinical management. We clustered all patients with CM in the Cancer Genome Atlas (TCGA) database based on cuproptosis-related genes (CRGs). Prognosis, immunotherapeutic effect, tumor microenvironment score, expression of CD274, CTLA4, and PDCD1, and abundance of CD8 + T infiltration in group A were higher than in group B. Using a combination of LASSO and COX regression analysis, we identified 10 molecules significant to prognosis from differentially expressed genes between the two groups and constructed a cuproptosis-related scoring system (CRSS). Compared with the American Joint Committee on Cancer (AJCC) staging system, CRSS more accurately stratified CM patient risk and guided immunotherapy. CRSS successfully stratified risk and predicted the effect of immunotherapy in 869 patients with eight CM immunotherapy datasets and multiple other tumor immunotherapy cohorts. The nomogram model, which combined AJCC stage and CRSS, greatly improved the ability and accuracy of prognosis prediction. In general, our cuproptosis-related scoring system and nomogram model accurately stratified risk in CM patients and effectively predicted prognosis and the effect of immunotherapy in CM patients.
Task-shifting and family planning continuation: contraceptive trajectories of women who received their method at a community-based event in Kinshasa, DRC
Authors: Hernandez Julie H. , LaNasa Katherine H. , Koba Tesky
Published: January 2023

While community-based interventions are a proven high-impact strategy to increase contraceptive uptake in low-income countries, their capacity to support women’s contraceptive choices (including continued use, switching and discontinuation) in the long run remains insufficiently discussed. This cohort study follows 883 women 3 and 6 months after they received a modern method during community campaigns organized in Kinshasa (D.R. Congo), to analyze their contraceptive trajectories and the factors associated with ever discontinuing contraceptive use in the first 6 months following a campaign. In the community-based distribution (CBD) model currently institutionalized in DRC, campaign clients are not provided with additional doses or support, besides baseline counseling, to (dis-)continue using the method they received, but must rely on Family Planning resources within the existing local health system. Almost a third (28.9%) of all women discontinued modern contraception during the study period, with much higher discontinuation rates for short-acting methods (38.7% for pills and up to 68.9% for DMPA-SC). Variables previously associated with high discontinuation (marital status, fertility intentions and side-effects) led to higher odds of “ever discontinuing”. However, these variables became non-significant when controlling for resupply issues. Women’s self-reported reasons for discontinuation confirmed the multivariate regression results. Detailed sub-analysis of resupply issues for pills, injectables and Cyclebeads pointed to the role of cost, unreliable campaign schedules and weak integration of community-based strategies into the formal health system. Extremely low rates of implants removal suggest similar access to FP services issues. The study highlights the need to identify CBD strategies best suited to support women’s choices and preferences towards successful contraceptive trajectories in fragile health systems.
Maternity protection entitlements for non-standard workers in low-and-middle-income countries and potential implications for breastfeeding practices: a scoping review of research since 2000
Authors: Pereira-Kotze Catherine , Feeley Alison , Doherty Tanya , Faber Mieke
Published: January 2023

Background

Recommended breastfeeding practices contribute to improved health of infants, young children, and mothers. Access to comprehensive maternity protection would enable working women to breastfeed for longer. Women working in positions of non-standard employment are particularly vulnerable to not accessing maternity protection entitlements. The objective of this scoping review was to determine the current research conducted on maternity protection available and accessible to non-standard workers in low-and-middle-income countries and any potential implications for breastfeeding practices.

Methods

Nine databases were searched using search terms related to maternity protection, non-standard employment, and breastfeeding. Documents in English published between January 2000 and May 2021 were included. The approach recommended by the Joanna Briggs Institute was used to select sources, extract, and present data. The types of participants included in the research were female non-standard workers of child-bearing age. The core concept examined by the scoping review was the availability and access to comprehensive maternity protection entitlements of pregnant and breastfeeding women. Research from low-and-middle-income countries was included. The types of evidence sources were limited to primary research.

Results

Seventeen articles were included for data extraction mainly from research conducted in Africa and Asia. Research on maternity protection for non-standard workers mostly focused on childcare. Components of maternity protection are inconsistently available and often inaccessible to women working in non-standard employment. Inaccessibility of maternity protection was described to disrupt breastfeeding both directly and indirectly, but certain characteristics of non-standard work were found to be supportive of breastfeeding.

Conclusions

Published information on maternity protection for non-standard workers is limited. However, the available information indicates that non-standard workers have inadequate and inconsistent access to maternity protection rights. The expansion of comprehensive maternity protection to all women working in positions of non-standard employment could encourage significant social and economic benefits.
Risk factors for recurrent infection in the surgical treatment of infected massive endoprostheses implanted for musculoskeletal tumours
Authors: Azamgarhi Tariq , Warren Simon , Aston Will , Pollock Rob , Gerrand Craig
Published: January 2023

Background

Infection is a devastating complication of endoprosthetic replacement (EPR) in orthopaedic oncology. Surgical treatments include debridement and/or one- or two-stage exchange. This study aims to determine the infection-free survival after surgical treatment for first and recurrent EPR infections and identify the risk factors associated with infection recurrence.

Methods

This single-centre cohort study included all patients with primary bone sarcomas or metastatic bone disease treated for infected EPR between 2010 and 2020. Variables included soft tissue status using McPherson classification, tumour type, silver coating, chemotherapy, previous surgery and microorganisms identified. Data for all previous infections were collected.

Survival analysis, with time to recurrent infection following surgical treatment, was calculated at 1, 2 and 4 years. Cox regression analysis was used to assess the influence of different variables on recurrent infection.

Results

The cohort included 99 patients with a median age of 44 years (29–58 IQR) at the time of surgical treatment. The most common diagnoses were osteosarcoma and chondrosarcoma.

One hundred and thirty-three surgical treatments for first or subsequent infections were performed. At 2 years of follow-up, overall success rates were as follows: two-stage exchange 55.3%, one-stage exchange 45.5%, DAIR with an exchange of modular components 44.6% and DAIR without exchange of modular components 24.7%.

Fifty-one (52%) patients were infection-free at the most recent follow-up. Of the remaining 48 patients, 27 (27%) were on antibiotic suppression and 21 (21%) had undergone amputation.

Significant risk factors for recurrent infection were the type of surgical treatment, with debridement alone as the highest risk (HR 4.75: 95%CI 2.43–9.30; P < 0.001); significantly compromised soft tissue status (HR 4.41: 95%CI 2.18–8.92; P = 0.001); and infections due to Enterococcus spp.. (HR 7.31: 95%CI 2.73–19.52); P = 0.01).

Conclusions

Two-stage exchange with complete removal of all components where feasible is associated with the lowest risk of recurrent infection. Poor soft tissues and enterococcal infections are associated with higher risks of recurrent infection. Treatment demands an appropriate multidisciplinary approach. Patients should be counselled appropriately about the risk of recurrent infection before embarking on complex treatment.
Cancer-educated mammary adipose tissue-derived stromal/stem cells in obesity and breast cancer: spatial regulation and function
Authors: Ritter Andreas , Kreis Nina-Naomi , Roth Susanne , Friemel Alexandra , Safdar Babek Kahn , Hoock Samira Catharina , Wildner Julia Maria , Allert Roman , Louwen Frank , Solbach Christine , Yuan Juping
Published: January 2023

Background

Breast cancer is the most frequently diagnosed cancer and a common cause of cancer-related death in women. It is well recognized that obesity is associated with an enhanced risk of more aggressive breast cancer as well as reduced patient survival. Breast adipose tissue-derived mesenchymal stromal/stem cells (bASCs) are crucial components of the tumor microenvironment. A key step initially involved in this process might be the de-differentiation of bASCs into tumor supporting phenotypes.

Methods

In the present work, we isolated bASCs from adipose tissues adjacent to the tumor (aT bASCs) from lean- (ln-aT bASCs, BMI ≤ 25) and breast cancer patients with obesity (ob-aT bASCs, BMI ≥ 35), and analyzed their phenotypes with functional assays and RNA sequencing, compared to their counterparts isolated from adipose tissues distant from the tumor (dT bASCs).

Results

We show that ln-aT bASCs are susceptible to be transformed into an inflammatory cancer-associated phenotype, whereas ob-aT bASCs are prone to be cancer-educated into a myofibroblastic phenotype. Both ln-aT- and ob-aT bASCs compromise their physiological differentiation capacity, and upregulate metastasis-promoting factors. While ln-aT bASCs stimulate proliferation, motility and chemoresistance by inducing epithelial-mesenchymal transition of low malignant breast cancer cells, ob-aT bASCs trigger more efficiently a cancer stem cell phenotype in highly malignant breast cancer cells.

Conclusion

Breast cancer-associated bASCs are able to foster malignancy of breast cancer cells by multiple mechanisms, especially, induction of epithelial-mesenchymal transition and activation of stemness-associated genes in breast cancer cells. Blocking the de-differentiation of bASCs in the tumor microenvironment could be a novel strategy to develop an effective intervention for breast cancer patients.

Significance

This study provides mechanistic insights into how obesity affects the phenotype of bASCs in the TME. Moreover, it highlights the molecular changes inside breast cancer cells upon cell-cell interaction with cancer-educated bASCs.

Graphical abstract
Prognostic significance and risk factors for pelvic and para-aortic lymph node metastasis in type I and type II ovarian cancer: a large population-based database analysis
Authors: Yu Hailin , Wang Jieyu , Wu Beibei , li Jun , Chen Ruifang
Published: January 2023

Background

To compare the prognosis of lymphatic metastasis in type I and type II epithelial ovarian cancer (OC) and to identify the risk factors for pelvic lymph node metastases (PLNs) and para-aortic lymph node metastases (PALNs).

Methods

Patients diagnosed with epithelial OC were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and cancer-specific survival (CSS) were estimated. The Cox proportional hazards regression model was used to identify independent predictors of survival.

Results

A total of 11,275 patients with OC were enrolled, including 31.2% with type I and 68.8% with type II. Type II and high tumour stage were risk factors for lymph node involvement (p < 0.05). The overall rate of lymph node metastasis in type I was 11.8%, and that in type II was 36.7%. In the type I group, the lymph node metastasis rates in stages T1, T2, T3 and TXM1 were 3.2%, 14.5%, 40.4% and 50.0%, respectively. In the type II group, these rates were 6.4%, 20.4%, 54.1% and 61.1%, respectively. Age and tumour size had little effect on lymph node metastasis, and grade 3 was not always a risk factor. For the type I group, the 10-year CSS rates of LN(-), PLN( +), PALN( +), and PLN + PALN( +) were 80.6%, 46.6%, 36.3%, and 32.3%, respectively. The prognosis of PLN ( +) was better than that of PALN ( +) in the type I group (p > 0.05). For the type II group, the 10-year CSS rates of LN(-), PLN( +), PALN( +), and PLN + PALN( +) were 55.6%, 18.5%, 25.7%, and 18.2%, respectively. PALN ( +) had a significantly better prognosis than PLN ( +) in the type II group (p < 0.05).

Conclusions

The clinical characteristics and prognoses of patients with type I and type II OC differed greatly. Patients with type II and higher tumour stages had poorer prognoses. Type I with PALN metastasis and type II with PLN metastasis indicated a worse prognosis. Patients with stage TI did not require lymph node dissection, especially in the type I group.
Pulmonary rehabilitation integrated coached exercise training for patients with COPD: a study protocol for a randomized controlled trial
Authors: Jing Yuting , Ma Yuying , Zhang Hongxing , Wu Zhenhu , Li Yongwen , Li Haoxuan , Huang Minling , Lin Lin , Xu Yinji
Published: January 2023

Background

Chronic obstructive pulmonary disease (COPD) is the most common chronic lung disease creating an immense burden on social health care systems. Pulmonary rehabilitation (PR) has proven to be effective in patients with COPD. However, exercise training as the basis of PR becomes extremely tedious, occasionally causing a loss of perseverance in patients. Therefore, we considered an approach that makes this technique interesting and easier to persist. The aim of this project was to explore an exercise training approach based on PR-integrated coached exercise training to promote the new exercise training approach as a form of group rehabilitation activity in the future.

Methods

Participants will be randomly divided into the trial and control groups. The trial group will be treated with PR-integrated coached exercise training (plus usual care). All exercise programs will be guided by sports coaches with a physical education background. Meanwhile, the control group will receive traditional PR and home exercises, including walking and swimming. The study will last for 12 weeks. The primary outcome measure is exercise tolerance using the 6-min walking test and secondary outcomes are the peak oxygen uptake of cardiopulmonary exercise tests, the COPD Assessment Test, and the St. Georges Respiratory Questionnaire. Other evaluated outcomes include changes in postbronchodilator forced expiratory volume at 1st second, forced vital capacity, body fat and muscle composition, and mental status measured using the Hamilton Anxiety and Depression Scales.

Discussion

This study provides a simple, feasible, repeatable, and fun exercise training approach. To the best of our knowledge, there are no randomized controlled trials in the existing literature on PR-integrated coached exercise. The protocol shared in our study can be used as a reference for exercise training in patients with COPD.

Trial registration

Ethical approval (BF2020-236–02) was obtained from the Guangdong Provincial Hospital of Chinese Medicine Human Research Ethics Committee. All participants signed an informed consent form. ChiCTR-2100043543. The registration date is 2021/02/21 and it is the third version.
Draft genome of Raoultella planticola, a high lead resistance bacterium from industrial wastewater
Authors: Elarabi Nagwa I. , Halema Asmaa A. , Abdelhadi Abdelhadi A. , Henawy Ahmed R. , Samir Omar , Abdelhaleem Heba A. R.
Published: January 2023

Isolation of heavy metals-resistant bacteria from their original habitat is a crucial step in bioremediation. Six lead (Pb) resistant bacterial strains were isolated and identified utilizing 16S rRNA to be Enterobacter ludwigii FACU 4, Shigella flexneri FACU, Microbacterium paraoxydans FACU, Klebsiella pneumoniae subsp. pneumonia FACU, Raoultella planticola FACU 3 and Staphylococcus xylosus FACU. It was determined that all these strains had their Minimum inhibitory concentration (MIC) to be 2500 ppm except R. planticola FACU 3 has a higher maximum tolerance concentration (MTC) up to 2700 ppm. We evaluated the survival of all six strains on lead stress, the efficiency of biosorption and lead uptake. It was found that R. planticola FACU 3 is the highest MTC and S. xylosus FACU was the lowest MTC in this evaluation. Therefore, transmission electron microscopy (TEM) confirmed the difference between the morphological responses of these two strains to lead stress. These findings led to explore more about the genome of R. planticola FACU 3 using illumine Miseq technology. Draft genome sequence analysis revealed the genome size of 5,648,460 bp and G + C content 55.8% and identified 5526 CDS, 75 tRNA and 4 rRNA. Sequencing technology facilitated the identification of about 47 genes related to resistance to many heavy metals including lead, arsenic, zinc, mercury, nickel, silver and chromium of R. planticola FACU 3 strain. Moreover, genome sequencing identified plant growth-promoting genes (PGPGs) including indole acetic acid (IAA) production, phosphate solubilization, phenazine production, trehalose metabolism and 4-hydroxybenzoate production genes and a lot of antibiotic-resistant genes.
14-3-3 proteins regulate cullin 7-mediated Eag1 degradation
Authors: Hsieh Chang-Heng , Chou Chia-Cheng , Fang Ya-Ching , Hsu Po-Hao , Chiu Yi-Hung , Yang Chi-Sheng , Jow Guey-Mei , Tang Chih-Yung , Jeng Chung-Jiuan
Published: January 2023

Background

Mutations in the human gene encoding the neuron-specific Eag1 (KV10.1; KCNH1) potassium channel are linked to congenital neurodevelopmental diseases. Disease-causing mutant Eag1 channels manifest aberrant gating function and defective protein homeostasis. Both the E3 ubiquitin ligase cullin 7 (Cul7) and the small acid protein 14-3-3 serve as binding partners of Eag1. Cul7 mediates proteasomal and lysosomal degradation of Eag1 protein, whereas over-expression of 14-3-3 notably reduces Eag1 channel activity. It remains unclear whether 14-3-3 may also contribute to Eag1 protein homeostasis.

Results

In human cell line and native rat neurons, disruptions of endogenous 14-3-3 function with the peptide inhibitor difopein or specific RNA interference up-regulated Eag1 protein level in a transcription-independent manner. Difopein hindered Eag1 protein ubiquitination at the endoplasmic reticulum and the plasma membrane, effectively promoting the stability of both immature and mature Eag1 proteins. Suppression of endogenous 14-3-3 function also reduced excitotoxicity-associated Eag1 degradation in neurons. Difopein diminished Cul7-mediated Eag1 degradation, and Cul7 knock-down abolished the effect of difopein on Eag1. Inhibition of endogenous 14-3-3 function substantially perturbed the interaction of Eag1 with Cul7. Further structural analyses suggested that the intracellular Per-Arnt-Sim (PAS) domain and cyclic nucleotide-binding homology domain (CNBHD) of Eag1 are essential for the regulatory effect of 14-3-3 proteins. Significantly, suppression of endogenous 14-3-3 function reduced Cul7-mediated degradation of disease-associated Eag1 mutant proteins.

Conclusion

Overall these results highlight a chaperone-like role of endogenous 14-3-3 proteins in regulating Eag1 protein homeostasis, as well as a therapeutic potential of 14-3-3 modulators in correcting defective protein expression of disease-causing Eag1 mutants.
Effect of implementation of mental health services within primary care on GP detection and treatment of mental disorders in Israel
Authors: Laufer Neil , Zilber Nelly , Jeczmien Pablo , Gilad Royi , Gur Shai , Munitz Hanan
Published: January 2023

Background

Psychiatric morbidity is frequent in primary care, but a substantial proportion of these psychiatric problems appear to be neither recognized nor adequately treated by GPs. There exists a number of models of introduction of mental health services (MHS) into primary care, but little data are available on their effect on GPs’ detection or management of mental disorders. The study aimed to measure the effect of referring patients to a psychiatrist within primary care (Shifted OutPatient model—SOP) or consultation of psychiatrists by the GPs (Psychiatric Community Consultation Liaison—PCCL) on the detection and treatment of mental disorders by GPs.

Methods

In six primary care clinics in Israel (three “SOP clinics” and three “PCCL clinics”), GP detection of mental disorders and treatment of GP-detected cases were evaluated before and after provision of 1-year MHS, according to GP questionnaires on a sample of primary care consecutive attenders whose psychological distress was determined according to the GHQ12 and psychiatric disorders according to the Composite International Diagnostic Interview.

Results

After model implementation, a significant reduction in detection of mental disorders was found in SOP clinics, while no significant change was found in PCCL clinics. No significant change in detection of distress was found in any clinic. An increase in referrals to MHS for GP-diagnosed depression and anxiety cases, a reduction in GP counselling for GP-detected cases and those with diagnosed anxiety, an increased prescription of antidepressants and a reduced prescription of antipsychotics were found in SOP clinics. In PCCL clinics, no significant changes in GP management were observed except an increase in referral of GP-diagnosed depression cases to MHS.

Conclusions

MHS models did not improve GP detection of mental disorders or distress, but possibly improved referral case mix. The SOP model might have a deskilling influence on GPs, resulting from less involvement in treatment, with decrease of detection and counselling. This should be taken into consideration when planning to increase referrals to a psychiatrist within primary care settings. Lack of positive effect of the PCCL model might be overcome by more intensive programs incorporating educational components.
Associations of socioeconomic status with infectious diseases mediated by lifestyle, environmental pollution and chronic comorbidities: a comprehensive evaluation based on UK Biobank
Authors: Ye Xiangyu , Wang Yidi , Zou Yixin , Tu Junlan , Tang Weiming , Yu Rongbin , Yang Sheng , Huang Peng
Published: January 2023

Background

Socioeconomic status (SES) inequity was recognized as a driver of some certain infectious diseases. However, few studies evaluated the association between SES and the burden of overall infections, and even fewer identified preventable mediators. This study aimed to assess the association between SES and overall infectious diseases burden, and the potential roles of factors including lifestyle, environmental pollution, chronic disease history.

Methods

We included 401,009 participants from the UK Biobank (UKB) and defined the infection status for each participant according to their diagnosis records. Latent class analysis (LCA) was used to define SES for each participant. We further defined healthy lifestyle score, environment pollution score (EPS) and four types of chronic comorbidities. We used multivariate logistic regression to test the associations between the four above covariates and infectious diseases. Then, we performed the mediation and interaction analysis to explain the relationships between SES and other variables on infectious diseases. Finally, we employed seven types of sensitivity analyses, including considering the Townsend deprivation index as an area level SES variable, repeating our main analysis for some individual or composite factors and in some subgroups, as well as in an external data from the US National Health and Nutrition Examination Survey, to verify the main results.

Results

In UKB, 60,771 (15.2%) participants were diagnosed with infectious diseases during follow-up. Lower SES [odds ratio (OR) = 1.5570] were associated with higher risk of overall infections. Lifestyle score mediated 2.9% of effects from SES, which ranged from 2.9 to 4.0% in different infection subtypes, while cardiovascular disease (CVD) mediated a proportion of 6.2% with a range from 2.1 to 6.8%. In addition, SES showed significant negative interaction with lifestyle score (OR = 0.8650) and a history of cancer (OR = 0.9096), while a significant synergy interaction was observed between SES and EPS (OR = 1.0024). In subgroup analysis, we found that males and African (AFR) with lower SES showed much higher infection risk. Results from sensitivity and validation analyses showed relative consistent with the main analysis.

Conclusions

Low SES is shown to be an important risk factor for infectious disease, part of which may be mediated by poor lifestyle and chronic comorbidities. Efforts to enhance health education and improve the quality of living environment may help reduce burden of infectious disease, especially for people with low SES.
Adjuvant Chemotherapy in Older Women With Early Breast Cancer
Authors: Trapani Dario
Published: January 2023

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology , to patients seen in their own clinical practice.

The clinical discussion on the adjuvant chemotherapy in older patients with breast cancer (BC) should routinely include comprehensive considerations of the health implications of competitive comorbidities, the safety of the treatment itself, and the likelihood that an appropriate dose intensity will be received (ie, relative dose intensity > 85%). All these factors have prognostic implications, as recently confirmed in the secondary analysis of the Hurria Older PatiEnts clinical trial. Full-informed, shared decision making is essential to provide best care. Our clinical approach for women with BC age ≥ 65 years is based on a standardized screening for frailty, triggering comprehensive geriatric assessment, as appropriate. We only recommend evidence-based regimens that have showed to reduce the risk of cancer recurrence and potentially increase overall survival. We frequently prefer docetaxel-cyclophosphamide, for hormone receptor–positive BC, on the basis of the subgroup analysis of the USOR-9735 study in older population. We avoid single agents (eg, capecitabine or weekly docetaxel), as showed to be inferior treatments in the CALGB-49907 and ELDA trials, and modified nonstandard regimens, for the lack of strong evidence in support.
The Prevalence and Prognosis of Microsatellite Instability-High/Mismatch Repair-Deficient Colorectal Adenocarcinomas in the United States
Authors: Gutierrez Catherine , Ogino Shuji , Meyerhardt Jeffrey A. , Iorgulescu J. Bryan
Published: January 2023

PURPOSE

Microsatellite instability (MSI) and DNA mismatch repair (MMR) status is an indispensable biomarker in the management of colorectal cancers. We therefore examined the epidemiology of MSI-high/MMR-deficient colorectal cancers in the United States.

METHODS

Adults presenting with colorectal adenocarcinoma in 2018-2019 were identified from the US National Cancer Database. Attributes associated with MSI-high/MMR-deficiency were identified using multivariable logistic regression and reported using average adjusted probabilities (%AAP) and 99.9% CIs. As a secondary aim, the survival associated with MSI/MMR status was assessed.

RESULTS

Among 101,259 colorectal adenocarcinomas in 2018-2019, 82.0% were microsatellite stable/MMR-proficient, 3.8% MSI-low, and 14.2% MSI-high/MMR-deficient—including 16.6%, 19.9%, 12.4%, and 7.3% of stage I, II, III, and IV cancers, respectively. In locoregional cancers, MSI-high/MMR-deficiency was associated with a bimodal age distribution, female sex, right-sided colonic origin, wild-type KRAS, and a prior diagnosis of cancer (all P < .001). By race/ethnicity, colorectal adenocarcinomas were MSI-high/MMR-deficient in 16.9%AAP of non-Hispanic White (99.9% CI, 16.5 to 17.4) patients, compared with 11.3%AAP of non-Hispanic Black (99.9% CI, 10.3 to 12.4), 12.4%AAP of Asian/Pacific Islander (99.9% CI, 10.5 to 14.3), and 15.1%AAP of Hispanic (99.9% CI, 13.4 to 16.7) patients (all P < .001). Histologically, MSI-high/MMR-deficiency was associated with increasing grade, from 11.3%AAP of well-differentiated tumors (99.9% CI, 10.2 to 12.4) to 28.4%AAP of poorly differentiated cases (99.9% CI, 27.1 to 29.8; P < .001). Compared with conventional histology (15.2%AAP, 99.9% CI, 14.8 to 15.6), medullary (41.1%AAP, 99.9% CI, 33.0 to 49.3; P < .001) and mucinous (24.6%AAP, 99.9% CI, 22.8 to 26.3; P < .001) subtypes—but not signet-ring cell histology (15.5%AAP, 99.9% CI, 11.6 to 19.4; P = .79)—were more frequently MSI-high/MMR-deficient when adjusting for clinicopathologic features including grade.

CONCLUSION

Our findings establish the epidemiology, features, and prognostic implications of MSI-high/MMR-deficiency among colorectal adenocarcinoma patients in the United States.
Homologous Recombination Repair Gene Mutations to Predict Olaparib Plus Bevacizumab Efficacy in the First-Line Ovarian Cancer PAOLA-1/ENGOT-ov25 Trial
Authors: Pujade-Lauraine Eric , Brown Jessica , Barnicle Alan , Wessen Jonathan , Lao-Sirieix Pierre , Criscione Steven W. , du Bois Andreas , Lorusso Domenica , Romero Ignacio , Petru Edgar , Yoshida Hiroyuki , Vergote Ignace , Colombo Nicoletta , Hietanen Sakari , Provansal Magali , Schmalfeldt Barbara , Pignata Sandro , Martín Lorente Cristina , Berton Dominique , Runnebaum Ingo B. , Ray-Coquard Isabelle
Published: January 2023

PURPOSE

The PAOLA-1/ENGOT-ov25 trial of maintenance olaparib plus bevacizumab for newly diagnosed advanced high-grade ovarian cancer demonstrated a significant progression-free survival (PFS) benefit over placebo plus bevacizumab, particularly in patients with homologous recombination deficiency (HRD)–positive tumors. We explored whether mutations in non- BRCA1 or BRCA2 homologous recombination repair (non–BRCA HRRm) genes predicted benefit from olaparib plus bevacizumab in PAOLA-1.

METHODS

Eight hundred and six patients were randomly assigned (2:1). Tumors were analyzed using the Myriad MyChoice HRD Plus assay to assess non–BRCA HRRm and HRD status; HRD was based on a genomic instability score (GIS) of ≥ 42. In this exploratory analysis, PFS was assessed in patients harboring deleterious mutations using six non–BRCA HRR gene panels, three devised for this analysis and three previously published.

RESULTS

The non–BRCA HRRm prevalence ranged from 30 of 806 (3.7%) to 79 of 806 (9.8%) depending on the gene panel used, whereas 152 of 806 (18.9%) had non‐ BRCA1 or BRCA2 mutation HRD-positive tumors. The majority of tumors harboring non–BRCA HRRm had a low median GIS; however, a GIS of > 42 was observed for tumors with mutations in five HRR genes ( BLM, BRIP1, RAD51C, PALB2, and RAD51D). Rates of gene-specific biallelic loss were variable (0% to 100%) in non–BRCA HRRm tumors relative to BRCA1-mutated (99%) or BRCA2-mutated (86%) tumors. Across all gene panels tested, hazard ratios for PFS (95% CI) ranged from 0.92 (0.51 to 1.73) to 1.83 (0.76 to 5.43).

CONCLUSION

Acknowledging limitations of small subgroup sizes, non–BRCA HRRm gene panels were not predictive of PFS benefit with maintenance olaparib plus bevacizumab versus placebo plus bevacizumab in PAOLA-1, irrespective of the gene panel tested. Current gene panels exploring HRRm should not be considered a substitute for HRD determined by BRCA mutation status and genomic instability testing in first-line high-grade ovarian cancer.
Income Sources Across Childhood in Families With Nonresident Fathers
Authors: Fomby Paula , Harvey Hope , Musick Kelly
Published: January 2023

Unpartnered mothers rely on formal and informal income sources to support their coresident minor children. Building on work focusing on selective populations and shorter time horizons, we describe the family income sources on which U.S. women and their minor children rely for up to 17 years following an unpartnered birth or union dissolution (Panel Study of Income Dynamics 2001–2017; N = 12,369 person-year records from 3,148 children). Using rich description and fixed-effect models, we treat family income as dynamic, mapping change in the share and amount of family income from multiple sources as children age and women gain employment experience; enter new unions; experience changes in eligibility for public support programs; and receive contributions from kin, friends, and other household members. A patchwork of income sources is the norm throughout childhood, with mothers' earnings nearly universal but insufficient as a sole source of family income. Maternal repartnering increases family income through new partner earnings but is accompanied by offsetting reductions in other income sources, particularly from outside the household. In the context of weak institutional support for U.S. families, families with nonresident fathers rely on a complex mix of income sources to make ends meet.
Multiportal Combined Endoscopic Endonasal and Transorbital Pathways: Qualitative and Quantitative Anatomic Studies of the “Connection” Skull Base Areas
Authors: Guizzardi Giulia , Prats-Galino Alberto , Mosteiro Alejandra , Santos Carlos , Topczewski Thomaz , Torales Jorge , Roldan Pedro , Reyes Luis , Di Somma Alberto , Enseñat Joaquim
Published: January 2023

BACKGROUND:

Combined endonasal and transorbital multiportal surgery has been recently described for selected skull base pathologies. Nevertheless, a detailed anatomic description and a quantitative comprehensive anatomic study of the skull base areas where these 2 endoscopic routes converge, a so-called connection areas, are missing in the scientific literature.

OBJECTIVE:

To identify all the skull base areas and anatomic structures where endonasal and transorbital endoscopic avenues could be connected and combined.

METHODS:

Five cadaveric specimens (10 sides) were used for dissection. Qualitative description and quantitative analysis of each connection areas were performed.

RESULTS:

At the anterior cranial fossa, the connection area was found at the level of the sphenoid planum; in the middle cranial fossa, it was at the Mullan triangle; finally, in the posterior cranial fossa, the connection area was just behind the medial portion of the petrous apex. The average extradural working areas through the transorbital approach were 4.93, 12.93, and 1.93 cm2and from the endonasal corridor were 7.75, 10.45, and 7.48 cm2at the level of anterior, middle, and posterior cranial fossae, respectively.

CONCLUSION:

The combined endonasal and transorbital endoscopic approach is an innovative entity of skull base neurosurgery. From the anatomic point of view, our study demonstrated the feasibility of this combined approach to access the entire skull base, by both corridors, identifying a working connection area in each cranial fossa. These data could be extremely useful during the surgical planning to predict which portion of a lesion could be removed through each route and to optimize patients' care.
Prenatal thyroid hormones accelerate postnatal growth and telomere shortening in wild great tits
Authors: Hsu Bin-Yan , Cossin-Sevrin Nina , Stier Antoine , Ruuskanen Suvi
Published: January 2023

The early-life environment is known to affect later-life health and disease, which could be mediated by the early-life programming of telomere length, a key hallmark of ageing. According to the fetal programming of telomere biology hypothesis, variation in prenatal exposure to hormones is likely to influence telomere length. Yet, the contribution of key metabolic hormones, i.e. thyroid hormones (THs), has been largely ignored. We recently showed that in contrast to predictions, exposure to elevated prenatal THs increased postnatal telomere length in wild collared flycatchers, but the generality of such effect, the underlying proximate mechanisms and consequences for survival have not been investigated. We therefore conducted a comprehensive study evaluating the impact of THs on potential drivers of telomere dynamics (growth, post-natal THs, mitochondria and oxidative stress), telomere length and medium-term survival using wild great tits as a model system. While prenatal THs did not significantly affect telomere length a week after hatching (i.e. day 7), they influenced postnatal telomere shortening (i.e. shorter telomeres at day 14 and the following winter) but not apparent survival. Circulating THs, mitochondrial density or oxidative stress biomarkers were not significantly influenced, whereas the TH-supplemented group showed accelerated growth, which may explain the observed delayed effect on telomeres. We discuss several alternative hypotheses that may explain the contrast with our previous findings in flycatchers. Given that shorter telomeres in early life tend to be carried until adulthood and are often associated with decreased survival prospects, the effects of prenatal THs on telomeres may have long-lasting effects on senescence.
Transcriptomic changes associated with maternal care in the brain of mouthbrooding cichlid Astatotilapia burtoni reflect adaptation to self-induced metabolic stress
Authors: Faber-Hammond Joshua J. , Renn Suzy C. P.
Published: January 2023

Parental care in Astatotilapia burtoni entails females protecting eggs and developing fry in a specialized buccal cavity in the mouth. During this mouthbrooding behavior, which can last 2–3 weeks, mothers undergo voluntary fasting accompanied by loss of body mass and major metabolic changes. Following release of fry, females resume normal feeding behavior and quickly recover body mass as they become reproductively active once again. In order to investigate the molecular underpinnings of such dramatic behavioral and metabolic changes, we sequenced whole-brain transcriptomes from females at four time points throughout their reproductive cycle: 2 days after the start of mouthbrooding, 14 days after the start of mouthbrooding, 2 days after the release of fry and 14 days after the release of fry. Differential expression analysis and clustering of expression profiles revealed a number of neuropeptides and hormones, including the strong candidate gene neurotensin, suggesting that molecular mechanisms underlying parental behaviors may be common across vertebrates despite de novo evolution of parental care in these lineages. In addition, oxygen transport pathways were found to be dramatically downregulated, particularly later in the mouthbrooding stage, while certain neuroprotective pathways were upregulated, possibly to mitigate negative consequences of metabolic depression brought about by fasting. Our results offer new insights into the evolution of parental behavior as well as revealing candidate genes that would be of interest for the study of hypoxic ischemia and eating disorders.
Primary-Market Auctions for Event Tickets: Eliminating the Rents of “Bob the Broker”?
Authors: Budish Eric , Bhave Aditya
Published: January 2023

Economists have long been puzzled by event-ticket underpricing: underpricing reduces revenue for the performer and encourages socially wasteful rent-seeking by ticket brokers. What about using an auction? This paper studies the introduction of auctions into this market by Ticketmaster in the mid-2000s. By combining primary-market auction data from Ticketmaster with secondary-market resale value data from eBay, we show that Ticketmaster’s auctions “worked”: they substantially improved price discovery, roughly doubled performer revenues, and, on average, nearly eliminated the potential arbitrage profits associated with underpriced tickets. We conclude by discussing why, nevertheless, the auctions failed to take off. (JEL D44, D47, L82)
Two-Stage Contests with Private Information
Authors: Kubitz Greg
Published: January 2023

In perfectly discriminating contests with private information, low-ability contestants prefer to appear strong, while high-ability contestants prefer to appear weak. In a two-stage contest, this leads to a unique symmetric equilibrium with partial pooling in the first stage. A higher output in the first contest leads to a weakly higher belief about the contestant’s ability entering the second contest. We characterize this unique equilibrium when cost of effort is linear and show how the prize allocation and type distribution impact contestants’ expected output, payoffs, and the probability of surprise victories. (JEL D44, D82, D83)
Compatibility Choices, Switching Costs, and Data Portability
Authors: Jeon Doh-Shin , Menicucci Domenico , Nasr Nikrooz
Published: January 2023

We study mix-and-match compatibility choices of firms selling complementary products in a dynamic setting. Contrary to what happens in a static setting where symmetric firms choose compatibility (Matutes and Regibeau 1988), when switching costs are high and firms make price discrimination based on past purchases, symmetric firms choose incompatibility to soften future competition if the discount factor is large, which harms consumers. Interoperability increases consumer surplus at least for high switching costs. Data portability, by reducing switching costs, induces the firms to choose compatibility more often but, given a compatibility regime, benefits consumers only if a nonnegative pricing constraint binds. (JEL D11, D21, D43, D82, L86)