bluuebunny/crossref_metadata_2025 huggingface dataset:
Invariant NKT cells dictate antitumor immunity elicited by a bispecific antibody cotargeting CD3 and BCMA
Authors: Casey Mika , Tu Cui , Harrison Simon J. , Nakamura Kyohei
Published: July 2022

CD3-engaging bispecific antibodies (BsAbs) have emerged as powerful therapeutic approaches by their ability to redirect T cells to eliminate tumor cells in a major histocompatibility complex–independent manner. However, how we can potentiate the efficacy of BsAbs remains largely unknown. To address this question, we investigated immunological mechanisms of action of a BsAb cotargeting CD3 and B-cell maturation antigen (BCMA) in syngeneic preclinical myeloma models. Treatment with the CD3/BCMA BsAb stimulated multiple CD3-expressing T-cell subsets and natural killer (NK) cells in the myeloma bone marrow (BM), highlighting its broad immunostimulatory effect. Notably, the BsAb-mediated immunostimulatory and antitumor effects were abrogated in mice lacking invariant NKT (iNKT) cells. Mechanistically, activation of iNKT cells and interleukin-12 production from dendritic cells (DCs) were crucial upstream events for triggering effective antitumor immunity by the BsAb. Myeloma progression was associated with a reduced number of BM iNKT cells. Importantly, the therapeutic efficacy of a single dose of CD3/BCMA BsAb was remarkably augmented by restoring iNKT cell activity, using adoptive transfer of α-galactosylceramide-loaded DCs. Together, these results reveal iNKT cells as critical players in the antitumor activity of CD3 engaging BsAbs and have important translational implications.
Quantitative proteomics analysis to assess protein expression levels in the ovaries of pubescent goats
Authors: Qin Ping , Ye Jing , Gong Xinbao , Yan Xu , Lin Maosen , Lin Tao , Liu Tong , Li Hailing , Wang Xiujuan , Zhu Yanyun , Li Xiaoqian , Liu Ya , Li Yunsheng , Ling Yinghui , Zhang Xiaorong , Fang Fugui
Published: July 2022

Background

Changes in the abundance of ovarian proteins play a key role in the regulation of reproduction. However, to date, no studies have investigated such changes in pubescent goats. Herein we applied isobaric tags for relative and absolute quantitation (iTRAQ) and liquid chromatography–tandem mass spectrometry to analyze the expression levels of ovarian proteins in pre-pubertal (n = 3) and pubertal (n = 3) goats.

Results

Overall, 7,550 proteins were recognized; 301 (176 up- and 125 downregulated) were identified as differentially abundant proteins (DAPs). Five DAPs were randomly selected for expression level validation by Western blotting; the results of Western blotting and iTRAQ analysis were consistent. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that DAPs were enriched in olfactory transduction, glutathione metabolism, and calcium signaling pathways. Besides, gene ontology functional enrichment analysis revealed that several DAPs enriched in biological processes were associated with cellular process, biological regulation, metabolic process, and response to stimulus. Protein–protein interaction network showed that proteins interacting with CDK1, HSPA1A, and UCK2 were the most abundant.

Conclusions

We identified 301 DAPs, which were enriched in olfactory transduction, glutathione metabolism, and calcium signaling pathways, suggesting the involvement of these processes in the onset of puberty. Further studies are warranted to more comprehensively explore the function of the identified DAPs and aforementioned signaling pathways to gain novel, deeper insights into the mechanisms underlying the onset of puberty.
Risk factors and mortality for elderly patients with bloodstream infection of carbapenem resistance Klebsiella pneumoniae: a 10-year longitudinal study
Authors: Chen Yili , Chen Yao , Liu Pingjuan , Guo Penghao , Wu Zhongwen , Peng Yaqin , Deng Jiankai , Kong Yannan , Cui Yingpeng , Liao Kang , Huang Bin
Published: July 2022

Background

Bloodstream infection (BSI) caused by carbapenem resistant Klebsiella pneumoniae (CRKP), especially in elderly patients, results in higher morbidity and mortality. The purpose of this study was to assess risk factors associated with CRKP BSI and short-term mortality among elderly patients in China.

Methods

In this retrospective cohort study, we enrolled 252 inpatients aged ≥ 65 years with BSI caused by KP from January 2011 to December 2020 in China. Data regarding demographic, microbiological characteristics, and clinical outcome were collected.

Result

Among the 252 BSI patients, there were 29 patients (11.5%) caused by CRKP and 223 patients (88.5%) by carbapenem-susceptible KP (CSKP). The overall 28-day mortality rate of elderly patients with a KP BSI episode was 10.7% (27/252), of which CRKP BSI patients (14 / 29, 48.3%) were significantly higher than CSKP patients (13 / 223, 5.83%) (P < 0.001). Hypertension (OR: 13.789, [95% CI: 3.883–48.969], P < 0.001), exposure to carbapenems (OR: 8.073, [95% CI: 2.066–31.537], P = 0.003), and ICU stay (OR: 11.180, [95% CI: 2.663–46.933], P = 0.001) were found to be associated with the development of CRKP BSI in elderly patients. A multivariate analysis showed that isolation of CRKP (OR 2.881, 95% CI 1.228–6.756, P = 0.015) and KP isolated in ICU (OR 11.731, 95% CI 4.226–32.563, P < 0.001) were independent risk factors for 28-day mortality of KP BSI.

Conclusion

In elderly patients, hypertension, exposure to carbapenems and ICU stay were associated with the development of CRKP BSI. Active screening of CRKP for the high-risk populations, especially elderly patients, is significant for early detection and successful management of CRKP infection.
Thyroid cancer incidence trend and association with obesity, physical activity in the United States
Authors: Chen Biaoyou , Xie Zhaomin , Duan Xuwei
Published: July 2022

Background

State-level racial/ethnic and age differences and the temporal trend of thyroid cancer (TC) incidence in the USA remain unknown. Our research purposes include: Characterizing state-level temporal variation in TC incidence; examining the disparities of TC incidence by state-level race/ethnicity and age; performing an ecological correlation between TC incidence and obesity/physical activity.

Methods

TC incidence data during 2000–2017 were extracted from the United States cancer statistics. Using joinpoint regression to evaluate TC incidence trends. Annual percent change (APC), average APC (AAPC) and incidence rates were calculated. The obesity prevalence and physical activity level at the state-level were extracted from Behavioral Risk Factor Surveillance System, and the association between state-level AAPC of TC and obesity/physical activity was tested by Pearson correlation coefficient.

Results

We found that the TC incidence had shown an overall downward trend in recent years, but 10 states continued increasing. There were significant differences in state-level race/ethnicity (non-Hispanic Whites as a reference) and age group (45–59 age group as a reference) incidence: Incidence Rate Ratio (IRR) was 0.4–1.2 for non-Hispanic Blacks, 0.7–1.6 for non-Hispanic Asian and Pacific Islanders, 0.4–1.2 for non-Hispanic American Indians/Alaskan Natives, and 0.5–1.3 for Hispanics. High IRR in young people were distributed in northern USA, while in older people were distributed in south. The state-level obesity/physical activity level and AAPC had a weak correlation (r = 0.34, P = 0.016) and inverse weak correlation (r = -0.29, P = 0.037), respectively. The AAPC of states with a consistent increasing trend had an extremely strong correlation with obesity prevalence (r = 0.80, p = 0.006), and an inverse strong correlation with physical activity level (r = -0.65, P = 0.04).

Conclusions

Thyroid cancer incidence in 10 states continued increasing. State-level variation in race/ethnicity and age group incidence were found. Lifestyle and environmental factors may interfere with the incidence trend of TC in the USA.
Efficacy of corticosteroids for hand osteoarthritis - a systematic review and meta-analysis of randomized controlled trials
Authors: Estee Mahnuma Mahfuz , Cicuttini Flavia M. , Page Matthew J. , Butala Anant D. , Wluka Anita E. , Hussain Sultana Monira , Wang Yuanyuan
Published: July 2022

Background

There is some evidence that corticosteroids may have a beneficial effect in hand osteoarthritis. We examined the efficacy of corticosteroids on symptoms and structural outcomes in hand osteoarthritis.

Methods

Ovid MEDLINE, Embase and Cochrane Central Register of Controlled Trials were searched from inception to October 2021 for randomized controlled trials investigating the efficacy of corticosteroids in hand osteoarthritis. Two authors independently screened records, extracted data, and assessed risk of bias using the RoB 2 tool. Standardized mean difference (SMD) or mean difference (MD) was calculated, and random-effects meta-analyses were performed.

Results

Of 13 included trials, 3 examined oral corticosteroids and clinical outcomes in any hand joints, 9 examined intra-articular injection of corticosteroids and clinical outcomes at the first carpometacarpal joint and one in the interphalangeal joints. In meta-analysis, oral corticosteroids reduced pain (SMD -0.53, 95% CI -0.79 to -0.28) and improved stiffness (MD -5.03, 95% CI -9.91 to -0.15; Australian Canadian Osteoarthritis Hand Index stiffness subscale) and function (SMD -0.37, 95% CI -0.63 to -0.12) at 4-6 weeks. However, there was no significant persistent effect on pain and function at 3 months which was 6-8 weeks after study medication was stopped. There was no significant effect of intra-articular corticosteroids on pain or function at 4-6 weeks or over 3-12 months in first carpometacarpal osteoarthritis. Two trials evaluated joint structure at 4-6 weeks: one study showed oral corticosteroids reduced synovial thickening, neither showed an effect on synovitis.

Conclusions

There was low-certainty evidence for a medium effect of oral corticosteroids on pain relief and stiffness improvement and small-to-medium effect on functional improvement at 4-6 weeks, with no significant effect for intra-articular corticosteroids. Corticosteroids had no significant effect on any outcomes over longer term (3-12 months) off treatment. No trials examined the effect of corticosteroids on disease progression. The role of corticosteroids in hand osteoarthritis is limited.
A novel multimodal needs assessment to inform the longitudinal education program for an international interprofessional critical care team
Authors: Li Heyi , Sun Yuqiang , Barwise Amelia , Cui Wenjuan , Dong Yue , Tekin Aysun , Yuan Qingzhong , Qiao Lujun , Gajic Ognjen , Niven Alexander
Published: July 2022

Background

The current global pandemic has caused unprecedented strain on critical care resources, creating an urgency for global critical care education programs. Learning needs assessment is a core element of designing effective, targeted educational interventions. In theory, multimodal methods are preferred to assess both perceived and unperceived learning needs in diverse, interprofessional groups, but a robust design has rarely been reported. Little is known about the best approach to determine the learning needs of international critical care professionals.

Method

We conducted multimodal learning needs assessment in a pilot group of critical care professionals in China using combined quantitative and qualitative methods. The assessments consisted of three phases: 1) Twenty statements describing essential entrustable professional activities (EPAs) were generated by a panel of critical care education experts using a Delphi method. 2) Eleven Chinese critical care professionals participating in a planned education program were asked to rank-order the statements according to their perceived learning priority using Q methodology. By-person factor analysis was used to study the typology of the opinions, and post-ranking focus group interviews were employed to qualitatively explore participants’ reasoning of their rankings. 3) To identify additional unperceived learning needs, daily practice habits were audited using information from medical and nursing records for 3 months.

Results

Factor analysis of the rank-ordered statements revealed three learning need patterns with consensual and divergent opinions. All participants expressed significant interest in further education on organ support and disease management, moderate interest in quality improvement topics, and relatively low interest in communication skills. Interest in learning procedure/resuscitation skills varied. The chart audit revealed suboptimal adherence to several evidence-based practices and under-perceived practice gaps in patient-centered communication, daily assessment of antimicrobial therapy discontinuation, spontaneous breathing trial, and device discontinuation.

Conclusions

We described an effective mixed-methods assessment to determine the learning needs of an international, interprofessional critical care team. The Q survey and focus group interviews prioritized and categorized perceived learning needs. The chart audit identified additional practice gaps that were not identified by the learners. Multimodal methods can be employed in cross-cultural scenarios to customize and better target medical education curricula.
The roles of personal interview and cognitive abilities at admission to medical school in predicting performance of medical students in their internal medicine sub-internship
Authors: Liberty Idit F. , Novack Lena , Hershkovitz Reli , Katz Amos
Published: July 2022

Background

The medical school admission process is complicated, perhaps reflecting unresolved debates concerning the most important skills necessary to become an ideal physician. The Goldman Medical School at Ben-Gurion University in Israel is known for placing great emphasis on the personal attributes of candidates in addition to their academic excellence. To this end, 1-h consecutive interviews are embedded in the admission process. This study aims to determine whether there is an association between candidates’ personal interview ratings and the ratings assigned to these students at the conclusion of their 6th year internal medicine sub-internship.

Methods

Our study sample included 136 students who were admitted to the medical school in 2015, and who completed their 6th year internal medicine sub-internship in 2019–2020. Our data were derived from the admissions information for each candidate and from structured interviews concerning medical competence and personal traits, which were completed by medical personnel who were in contact with these students during their clinical rounds.

Results

Higher interview ratings of candidates during the admission process were associated with a higher probability that students would be evaluated as top-rated internists 6 years later (Odds Ratio (OR) = 9.4, p-value = 0.049), independent of gender (OR for male vs female = 0.2, p-value = 0.025) and age (OR = 1.3 per each year, p-value = 0.115). Although significant, the numeric difference in interview rating was relatively small (median 9.5 and 9.4 for top-rated and not top-rated internists, respectively).

Conclusions

Our study shows that high personal interview ratings assigned to candidates as part of the medical school admission process are predictive of high performance ratings of students after they complete their 6th year internal medicine sub-internships. These findings demonstrate the value and importance of using semi-structured personal interviews in the medical school admission process.
Staff and patient experience of the implementation and delivery of a virtual health care home monitoring service for COVID-19 in Melbourne, Australia
Authors: Jessup R. L. , Awad N. , Beauchamp A. , Bramston C. , Campbell D. , Semciw Al , Tully N. , Fabri A. M. , Hayes J. , Hull S. , Clarke A. C.
Published: July 2022

Background

Provision of virtual health care (VHC) home monitoring for patients who are experiencing mild to moderate COVID-19 illness is emerging as a central strategy for reducing pressure on acute health systems. Understanding the enablers and challenges in implementation and delivery of these programs is important for future implementation and re-design. The aim of this study was to explore the perspectives of staff involved with the implementation and delivery, and the experience of patients managed by, a VHC monitoring service in Melbourne, Australia during the COVID-19 pandemic.

Methods

A descriptive qualitative approach informed by naturalist inquiry was used. Staff interviews were analysed using the Consolidated Framework for Implementation Research (CFIR). Patient experience was captured using a survey and descriptive statistics were used to describe categorical responses while content analysis was used to analyse free text responses as they related to the CFIR. Finally, data from the interviews and patient experience were triangulated to see if patient experience validated data from staff interviews.

Results

All 15 staff were interviewed, and 271 patients were surveyed (42%). A total of four final overarching themes emerged: service implementation enablers, service delivery benefits for patients, fragmentation of care, and workforce strengths. 19 subthemes aligned with 18 CFIR constructs from staff and patient data.

Conclusion

Rapid implementation was enabled through shared resources, dividing implementation tasks between senior personnel, engaging furloughed healthcare staff in design and delivery, and having a flexible approach that allowed for ongoing improvements. Benefits for patients included early identification of COVID-19 deterioration, as well as provision of accurate and trustworthy information to isolate safely at home. The main challenges were the multiple agencies involved in patient monitoring, which may be addressed in the future by attributing responsibility for monitoring to a single agency.
Willingness to pay for social health insurance and its associated factors among public servants in Addis Ababa, Ethiopia: a cross-sectional study
Authors: Kokebie Melkamu Ayalew , Abdo Ziyad Ahmed , Mohamed Shikur , Leulseged Belayneh
Published: July 2022

Background

As a means of establishing a sustained and fair health care financing system, Ethiopia has planned and ratified a legal framework to introduce a social health insurance program for employees of the formal sector to protect them against financial and health burdens. However, the implementation has been delayed due to the resistance of public servants to pay the proposed premium. The aim of this study was to estimate the magnitude of willingness to pay the proposed amount of premium set by the government for the social health insurance program and the factors associated with it among public servants in Addis Ababa, Ethiopia.

Methods

An institution-based cross-sectional study design was used to conduct the study. Multistage sampling was employed to select a total of 503 from 12 randomly selected public sectors. Data were collected using pretested, interviewer-administered structured questionnaires. A contingent valuation method with an iterative bidding game was used to elicit willingness to pay. Finally, logistic regression analysis was used to identify independent predictors of willingness to pay. Statistical significance was considered at P < 0.05 with adjusted odds ratios calculated at 95% CIs.

Results

Only 35.4% were willing to pay the proposed premium (3% of their monthly salary). Those who had children from 6–18 years old (AOR = 3.252; 95% CI: 1.15, 9.22), had a history of unaffordable health service costs during the last 12 months (AOR = 9.631; 95% CI: 4.12, 22.52), and had prior information about the social health insurance program (AOR = 11.011, 95% CI. 3.735–32.462) were more likely to pay for the proposed social health insurance program compared to their counterparts.

Conclusion

The willingness to pay the proposed amount premium for social health insurance among public servants in Addis Ababa was very low that implies the implementation will be challenging. Thus, the government of Ethiopia should consider reviewing the amount of premium contributions expected from employees before implementing the social health insurance scheme.
Targeting p53–MDM2 interaction by small-molecule inhibitors: learning from MDM2 inhibitors in clinical trials
Authors: Zhu Haohao , Gao Hui , Ji Yingying , Zhou Qin , Du Zhiqiang , Tian Lin , Jiang Ying , Yao Kun , Zhou Zhenhe
Published: July 2022

p53, encoded by the tumor suppressor gene TP53, is one of the most important tumor suppressor factors in vivo and can be negatively regulated by MDM2 through p53–MDM2 negative feedback loop. Abnormal p53 can be observed in almost all tumors, mainly including p53 mutation and functional inactivation. Blocking MDM2 to restore p53 function is a hotspot in the development of anticancer candidates. Till now, nine MDM2 inhibitors with different structural types have entered clinical trials. However, no MDM2 inhibitor has been approved for clinical application. This review focused on the discovery, structural modification, preclinical and clinical research of the above compounds from the perspective of medicinal chemistry. Based on this, the possible defects in MDM2 inhibitors in clinical development were analyzed to suggest that the multitarget strategy or targeted degradation strategy based on MDM2 has the potential to reduce the dose-dependent hematological toxicity of MDM2 inhibitors and improve their anti-tumor activity, providing certain guidance for the development of agents targeting the p53–MDM2 interaction.
The gut–liver axis in sepsis: interaction mechanisms and therapeutic potential
Authors: Zhang Xue , Liu Hong , Hashimoto Kenji , Yuan Shiying , Zhang Jiancheng
Published: July 2022

Sepsis is a potentially fatal condition caused by dysregulation of the body's immune response to an infection. Sepsis-induced liver injury is considered a strong independent prognosticator of death in the critical care unit, and there is anatomic and accumulating epidemiologic evidence that demonstrates intimate cross talk between the gut and the liver. Intestinal barrier disruption and gut microbiota dysbiosis during sepsis result in translocation of intestinal pathogen-associated molecular patterns and damage-associated molecular patterns into the liver and systemic circulation. The liver is essential for regulating immune defense during systemic infections via mechanisms such as bacterial clearance, lipopolysaccharide detoxification, cytokine and acute-phase protein release, and inflammation metabolic regulation. When an inappropriate immune response or overwhelming inflammation occurs in the liver, the impaired capacity for pathogen clearance and hepatic metabolic disturbance can result in further impairment of the intestinal barrier and increased disruption of the composition and diversity of the gut microbiota. Therefore, interaction between the gut and liver is a potential therapeutic target. This review outlines the intimate gut–liver cross talk (gut–liver axis) in sepsis.
Molecular epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae among children in China
Authors: Jin Zhengjiang , Wang Zhenhui , Gong Lin , Yi Lu , Liu Nian , Luo Lan , Gong Wenting
Published: July 2022

Klebsiella pneumoniae infection and antimicrobial resistance among children are major concerns. The occurrence of hypervirulent K. pneumoniae (hvKp) infections is gradually increasing worldwide, and disinfectant resistance is also being reported. Carbapenem- and disinfectant-resistant hvKp infection has made clinical treatment and nosocomial infection control among children increasingly challenging. In this study, whole-genome sequencing was conducted among 34 Carba NP-positive carbapenem-resistant K. pneumoniae (CRKP) strains, and the distribution of antibiotic resistance genes, virulence genes and disinfectant resistance genes was determined. Eleven distinct STs were identified, and most of them were ST11 (58.8%). Among the carbapenem resistance genes, KPC-2 was predominant (61.8%), followed by NDM-1 (26.5%) and IPM-4 (11.8%), and no other carbapenemase genes were found. Twelve virulence genes were investigated. All 34 CRKP strains carried the following virulence genes: rcsA/B, entA, fimA/H and mrkA/D. The gene iucB was present in only 3 (8.9%) CRKP strains. The positive detection rates of the iroN and ybtA genes were 94.1% and 64.7%, respectively. None of the strains was found to carry the rmpA and iroB genes. Two disinfectant resistance genes were investigated in this study. Twenty-one (61.8%) strains carried both the qacE and cepA disinfectant resistance genes, 13 (38.2%) CRKP strains carried only the cepA gene, and no strains with only the qacE gene was detected. The correlations among virulence, drug resistance and disinfectant tolerance showed that the virulence and disinfectant resistance genes were distinct among several types of carbapenemase-producing CRKP strains.
Lipid metabolism and m6A RNA methylation are altered in lambs supplemented rumen-protected methionine and lysine in a low-protein diet
Authors: Gebeyew Kefyalew , Yang Chao , Mi Hui , Cheng Yan , Zhang Tianxi , Hu Fan , Yan Qiongxian , He Zhixiong , Tang Shaoxun , Tan Zhiliang
Published: July 2022

Background

Methionine or lysine has been reported to influence DNA methylation and fat metabolism, but their combined effects in N6-methyl-adenosine (m6A) RNA methylation remain unclarified. The combined effects of rumen-protected methionine and lysine (RML) in a low-protein (LP) diet on lipid metabolism, m6A RNA methylation, and fatty acid (FA) profiles in the liver and muscle of lambs were investigated. Sixty-three male lambs were divided into three treatment groups, three pens per group and seven lambs per pen. The lambs were fed a 14.5% crude protein (CP) diet (adequate protein [NP]), 12.5% CP diet (LP), and a LP diet plus RML (LP + RML) for 60 d.

Results

The results showed that the addition of RML in a LP diet tended to lower the concentrations of plasma leptin (P = 0.07), triglyceride (P = 0.05), and non-esterified FA (P = 0.08). Feeding a LP diet increased the enzyme activity or mRNA expression of lipogenic enzymes and decreased lipolytic enzymes compared with the NP diet. This effect was reversed by supplementation of RML with a LP diet. The inclusion of RML in a LP diet affected the polyunsaturated fatty acids (PUFA), n-3 PUFA, and n-6 PUFA in the liver but not in the muscle, which might be linked with altered expression of FA desaturase-1 (FADS1) and acetyl-CoA carboxylase (ACC). A LP diet supplemented with RML increased (P < 0.05) total m6A levels in the liver and muscle and were accompanied by decreased expression of fat mass and obesity-associated protein (FTO) and alkB homologue 5 (ALKBH5). The mRNA expressions of methyltransferase-like 3 (METTL3) and methyltransferase-like 14 (METTL14) in the LP + RML diet group were lower than those in the other two groups. Supplementation of RML with a LP diet affected only liver YTH domain family (YTHDF2) proteins (P < 0.05) and muscle YTHDF3 (P = 0.09), which can be explained by limited m6A-binding proteins that were mediated in mRNA fate.

Conclusions

Our findings showed that the inclusion of RML in a LP diet could alter fat deposition through modulations of lipogenesis and lipolysis in the liver and muscle. These changes in fat metabolism may be associated with the modification of m6A RNA methylation.

Graphical abstract

A systematic graph illustrates the mechanism of dietary methionine and lysine influence on lipid metabolism and M6A. The green arrow with triangular heads indicates as activation and brown-wine arrows with flat heads indicates as suppression.
A novel E-cadherin/SOX9 axis regulates cancer stem cells in multiple myeloma by activating Akt and MAPK pathways
Authors: Samart Parinya , Rojanasakul Yon , Issaragrisil Surapol , Luanpitpong Sudjit
Published: July 2022

Cancer stem cells (CSCs) have been identified in multiple myeloma (MM) and are widely regarded as a key driver of MM initiation and progression. E-cadherin, in addition to its established role as a marker for epithelial-mesenchymal transition, also plays critical roles in controlling the aggressive behaviors of various tumor cells. Here, we show that depletion of E-cadherin in MM cells remarkably inhibited cell proliferation and cell cycle progression, in part through the decreased prosurvival CD138 and Bcl-2 and the inactivated Akt and MAPK pathways. CSC features, including the ability of the cells to form clonogenic colonies indicative of self-renewal and side population, were greatly suppressed upon the depletion of E-cadherin and subsequent loss of SOX9 stem-cell factor. We further provide evidence that SOX9 is a downstream target of E-cadherin-mediated CSC growth and self-renewal—ectopic re-expression of SOX9 in E-cadherin-depleted cells rescued its inhibitory effects on CSC-like properties and survival signaling. Collectively, our findings unveil a novel regulatory mechanism of MM CSCs via the E-cadherin/SOX9 axis, which could be important in understanding the long-term cell survival and outgrowth that leads to relapsed/refractory MM.
First descriptions of the seasonal habitat use and residency of scalloped hammerhead (Sphyrna lewini) and Galapagos sharks (Carcharhinus galapagensis) at a coastal seamount off Japan
Authors: Jacoby David M. P. , Watanabe Yuuki Y. , Packard Tre , Healey Mark , Papastamatiou Yannis P. , Gallagher Austin J.
Published: July 2022

Background

The Northwestern Pacific is a data-poor region for studies into the movements and habitat use of open ocean and pelagic sharks. However, this region experiences considerable pressure from commercial fishing. Therefore, shark movement data from this region carry significant implications for conservation and management, particularly for threatened species. Here, we provide the first data on seasonal residency and movements of scalloped hammerhead (Sphyrna lewini) and Galapagos sharks (Carcharhinus galapagensis), using acoustic and satellite telemetry, and dive logbooks, off Japan.

Results

Eight female sharks, four of each species, were tagged around a coastal seamount off southeastern Japan (Mikomoto Island) in August 2015, and monitored for a period of up to 363 days using an array of six receivers around the island. Analyses of the more abundant scalloped hammerhead acoustic data suggest high seasonal residency predominantly from August to November associated with lower chlorophyll-aconcentrations, before sharks then leave the island and return the following summer. Residency for scalloped hammerhead sharks were highest among those receivers closest to the Kuroshio Current, which produces strong coastal upwelling, however SST was not found to be predictive of occurrence at Mikomoto. Shark presence was corroborated by analysis of dive-log data from a local ecotourism operator. We also produced two unique satellite tracks, whereby a scalloped hammerhead exhibited a 200-km dispersal into a coastal embayment west of the tagging location and a Galapagos shark migrated over 800 km offshore into the high seas.

Conclusion

This study provided some of the first behavioral and movement data for scalloped hammerhead and Galapagos sharks in Japan. Our findings suggest varying spatial and temporal visitation of two shark species to a coastal seamount, underscored by some degree of seasonal residency and site fidelity and linked, for scalloped hammerhead sharks at least, to varying productivity. Furthermore, we provided preliminary evidence for long-distance dispersal of these species, and some site fidelity to seamounts in the region. This study highlights the importance of describing shark movements to aid in filling critical data gaps for poorly understood, endemic populations of threatened species.
The voices of incarcerated women at the forefront of parenting program development: a trauma-informed approach to education
Authors: Lovell Belinda J. , Steen Mary P. , Brown Angela E. , Esterman Adrian J.
Published: July 2022

Background

The lives of women experiencing incarceration are complex, impacting many aspects of parenting. Incarceration can present an opportunity for women to access parenting education. However, their specific needs have to be considered. Few parenting programs for women experiencing incarceration have involved the women as part of their development.

Methods

Six focus groups were conducted in a prison setting involving thirty-one women to explore and understand their parenting education needs.

Results

Four main themes were identified to reflect the complex lives of the women and their parenting education needs. These themes were: working towards a positive self, communication as a lifeline, supporting and nurturing their children and hopefulness and reconnecting. The trauma women experienced in their lives was apparent during discussions.

Conclusion

Women requested a non-judgmental parenting program to be developed to meet their specific needs and circumstances. The program needed to be designed to enable them to share stories with women in similar situations. Women gave insights into some of the specific content and topics they would like included in a parenting program. The women revealed experiences of trauma in their lives, demonstrating the importance of the need for a trauma informed approach to parenting education.
Goal setting with young people for anxiety and depression: What works for whom in therapeutic relationships? A literature review and insight analysis
Authors: Jacob Jenna , Stankovic Milos , Spuerck Inga , Shokraneh Farhad
Published: July 2022

Background

Goal setting and goal-focused work is widely used in young people’s mental health settings. However, little is known about how, why or for whom this is helpful. This study aims to explore the mechanisms of collaborative goal setting as part of therapeutic relationships: is it helpful for young people experiencing anxiety and/or depression, how and why/not, for whom, and under what circumstances?

Methods

Online database searches generated 10,907 records. Seven unique studies are included, combined with insight analysis from directed discussions with international advisors with lived experience of anxiety and/or depression and therapy (N = 8; mean age = 20.8), and mental health academics/clinicians (N = 6).

Results

Findings are presented as a narrative synthesis and suggest that goal setting is helpful to young people experiencing anxiety and/or depression because it helps build good therapeutic relationships through open communication and building trust. Goal setting helps make things more manageable, enabling young people to feel supported and have ownership of their care. Individual preferences, or high levels of distress, trauma, low confidence, hopelessness, negative past experiences of goal setting, perfectionism, and rumination are considered limiting factors to goal setting. Additionally, contextual factors including country and long-term therapy are explored.

Conclusion

Whilst the resultant sample is small, emphasis on the voices of young people in the research is both prominent and of paramount importance. Several key literature gaps are identified, including evidenced links to the reduction in symptoms. Priority must be given to researching unhelpful mechanisms of goal setting for young people experiencing anxiety and/or depression, to avoid any potential iatrogenic effects.
Examine the relationships between health-related quality of life, achievement motivation and job performance: the case of Taiwan hospitality industry
Authors: Ni Wei-Ya , Ng Eric , Chiang Yi-Te , LePage Ben A. , Yang Feng-Hua , Fang Wei-Ta
Published: July 2022

Background

Employees are considered as one of the most important assets in many organizations, and their health well-being is critical to help achieve a sustainable and motivated workforce that is committed to delivering quality hospitality services through enhanced performance and productivity. Given the extent of the challenges and impact presented by the COVID-19 pandemic to the hospitality industry, it is timely to gain further insights on employees’ health well-being. The key purpose of this study is to examine the relationships between health-related quality of life, achievement motivation and job performance in the Taiwan hospitality industry, to acquire a better understanding of their relationships through the job performance pathway models.

Methods

This study has used a purposeful sampling technique to select the 10 highest-earning hospitality companies in Taiwan. A total of 292 questionnaires were collected from the employees of these hospitality companies. Based on the multi-dimensional concept of health-related quality of life (HRQoL), the relationships between the five key dimensions (i.e. psychological health, physical health, social health, achievement motivation, and job performance) were examined. To measure these dimensions, the survey questions were adapted from previous research such as the World Health Organization’s WHOQOL-BREF scale, Minnesota Satisfaction Questionnaire. Partial least squares - Structural Equation Modeling method was used to explore these dimensions, and two job performance pathway models (for manager and staff) were subsequently developed.

Results and conclusions

Findings showed that psychological health directly affected the manager’s job performance and physical health had a similar effect through social health. While psychological health had not affected the staff’s job performance, but it could affect achievement motivation through both direct and indirect effects of social health. The pathway models that were developed indicated that the manager’s job performance was mainly affected by psychological health and social health, whereas the key dimension that had affected the staff’s job performance was achievement motivation.
circCYP24A1 promotes Docetaxel resistance in prostate Cancer by Upregulating ALDH1A3
Authors: Yin Haoli , Qin Haixiang , Yang Lei , Chen Mengxia , Yang Yang , Zhang Wenlong , Hao Jiange , Lu Qun , Shi Jingyan , Zhuang Junlong , Qiu Xuefeng , Guo Hongqian
Published: July 2022

Background

Docetaxel (DTX) is the most widely prescribed first-line chemotherapy for advanced prostate cancer (PCa). Unfortunately, DTX resistance invariably emerges, leading to worse prognosis of PCa. Growing evidence has shown that circRNAs had complex spatiotemporal specificity during the tumor development and oncogenesis. This study was designed to investigate the biological functions and possible molecular mechanisms of circRNAs in DTX resistance of PCa.

Methods

circRNAs in established DTX-resistant DU145 cell line were identified by RNA sequencing. Biological function of circCYP24A1 was verified in vitro and in vivo. The potential role of circCYP24A1 in the development of DTX-resistant PCa was investigated via dual-luciferase reporter assays, RIP assays and RNA pull-down assays. Univariate and multivariate logistic regression analyses was used to predict DTX-chemotherapy response based on patients’ clinical and biological information.

Results

CircCYP24A1 was identified to be upregulated in DTX-resistant DU145 cells. Upregulated circCYP24A1 was found to suppress the DTX chemosensitivity in vitro and in vivo. Furthermore, we found that circCYP24A1 promoted DTX resistance in PCa via regulating ALDH1A3 expression by sponging miR-1301-3p and activating PI3K/AKT/mTOR signaling pathway. Statistical analyses elucidated that circCYP24A1 was an independent risk factor to predict DTX response (OR = 0.165; 95% CI: 0.038–0.723; P = 0.017).

Conclusions

This study demonstrated that circCYP24A played an essential role in DTX resistance in PCa, suggesting that circCYP24A1 could be a promising biomarker to predict DTX response and a potential therapeutic target in PCa patients resistant to DTX chemotherapy.
IGSF11 and VISTA: a pair of promising immune checkpoints in tumor immunotherapy
Authors: Tang Xi-Yang , Xiong Yan-Lu , Shi Xian-Gui , Zhao Ya-Bo , Shi An-Ping , Zheng Kai-Fu , Liu Yu-Jian , Jiang Tao , Ma Nan , Zhao Jin-Bo
Published: July 2022

Immunotherapy has become the major treatment for tumors in clinical practice, but some intractable problems such as the low response rate and high rates of immune-related adverse events still hinder the progress of tumor immunotherapy. Hence, it is essential to explore additional immunotherapy treatment targets. In this review, we focus on the structure, expression and expression-related mechanisms, interactions, biological functions and the progress in preclinical/clinical research of IGSF11 and VISTA in tumors. We cover the progress in recent research with this pair of immune checkpoints in tumor immune regulation, proliferation, immune resistance and predictive prognosis. Both IGSF11 and VISTA are highly expressed in tumors and are modulated by various factors. They co-participate in the functional regulation of immune cells and the inhibition of cytokine production. Besides, in the downregulation of IGSF11 and VISTA, both inhibit the growth of some tumors. Preclinical and clinical trials all emphasize the predictive role of IGSF11 and VISTA in the prognosis of tumors, and that the predictive role of the same gene varies from tumor to tumor. At present, further research is proving the enormous potential of IGSF11 and VISTA in tumors, and especially the role of VISTA in tumor immune resistance. This may prove to be a breakthrough to solve the current clinical immune resistance, and most importantly, since research has focused on VISTA but less on IGSF11, IGSF11 may be the next candidate for tumor immunotherapy.
High expression of TMEM244 is associated with poor overall survival of patients with T-cell lymphoma
Authors: Chen Cunte , Chen Shaohua , Luo Gengxin , Wang Liang , Zeng Chengwu , Przybylski Grzegorz K. , Li Yangqiu
Published: July 2022

T-cell lymphoma (TCL) is an aggressive and genetically heterogeneous malignancy with adverse clinical outcomes; thus, it is worth exploring biomarkers for risk stratification. Previous studies have demonstrated that transmembrane protein 244 gene (TMEM244) is ectopically expressed in Sézary syndrome (SS). In this study, the expression level of TMEM244 and its prognostic value for TCL patients was explored by analyzing RNA-seq data of two large datasets (GSE132550 and GSE113113) containing 129 TCL patients and 13 healthy individuals (HIs) from the Gene Expression Omnibus (GEO) database, the PRJCA002270 dataset containing 124 patients with T-cell acute lymphoblastic leukemia (T-ALL) from the BioProject database, and peripheral blood (PB) samples of 24 TCL and 29 T-ALL patients, as well as 11 normal CD3 + T-cells from our clinical center (JNU). The results suggested that TMEM244 was significantly up-regulated in TCL patients compared with normal CD3 + T-cells or T-ALL in the JNU, GSE132550 and GSE113113 datasets (P < 0.05). However, TMEM244 shows no expression in patients with T-ALL in the JNU-T-ALL and PRJCA002270 datasets. The receiver operating characteristic (ROC) curve analysis indicated that TMEM244 expression had a very high accuracy in diagnosing TCL compared with T-ALL (area under the curve (AUC): 99.4%; P < 0.001). Importantly, high TMEM244 expression was significantly associated with poor OS and shorter 5-year restricted mean survival time (RMST) in TCL patients, especially those treated with chemotherapy. In summary, TMEM244 is also expressed in other types of TCL besides SS, but not in T-ALL. High TMEM244 expression is associated with poor OS in TCL patients, which might be a novel biomarker for prognostic stratification in TCL patients and facilitate the design of novel therapies.
ZG16 promotes T-cell mediated immunity through direct binding to PD-L1 in colon cancer
Authors: Meng Hui , Yao Wu , Yin Yuhui , Li Yizhen , Ding Yi , Wang Liang , Zhang Mingzhi
Published: July 2022

Immunotherapy using programmed cell death 1 (PD1) inhibitors has shown great efficacy in colorectal cancer patients harboring mismatch-repair-deficient (dMMR) and microsatellite instability-high (MSI-H) alterations. We previously showed a negative correlation of zymogen granule protein 16 (ZG16) with programmed death-ligand 1 (PD-L1) expression in patients with colorectal cancer. However, how ZG16 regulates PD-L1 expression is unclear. In this study, we showed that ZG16 can directly bind to glycosylated PD-L1 through its lectin domain, leading to PD-L1 degradation. Mutations on the lectin domain of ZG16 largely inhibit the interaction between ZG16 and PD-L1. Importantly, ZG16 overexpression suppressed tumor growth in two syngeneic mouse models through blockage of PD-L1 expression in cancer cells meanwhile suppression of PD1 expression in T cells. We also showed that ZG16 could improve the effect of chemotherapy and may be delivered as a protein to serve as an immune checkpoint inhibitor to promote T-cell mediated immunity.
Real-time event detection in social media streams through semantic analysis of noisy terms
Authors: Kolajo Taiwo , Daramola Olawande , Adebiyi Ayodele A.
Published: July 2022

Interactions via social media platforms have made it possible for anyone, irrespective of physical location, to gain access to quick information on events taking place all over the globe. However, the semantic processing of social media data is complicated due to challenges such as language complexity, unstructured data, and ambiguity. In this paper, we proposed the Social Media Analysis Framework for Event Detection (SMAFED). SMAFED aims to facilitate improved semantic analysis of noisy terms in social media streams, improved representation/embedding of social media stream content, and improved summarization of event clusters in social media streams. For this, we employed key concepts such as integrated knowledge base, resolving ambiguity, semantic representation of social media streams, and Semantic Histogram-based Incremental Clustering based on semantic relatedness. Two evaluation experiments were conducted to validate the approach. First, we evaluated the impact of the data enrichment layer of SMAFED. We found that SMAFED outperformed other pre-processing frameworks with a lower loss function of 0.15 on the first dataset and 0.05 on the second dataset. Second, we determined the accuracy of SMAFED at detecting events from social media streams. The result of this second experiment showed that SMAFED outperformed existing event detection approaches with better Precision (0.922), Recall (0.793), and F-Measure (0.853) metric scores. The findings of the study present SMAFED as a more efficient approach to event detection in social media.