bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance Outcomes and Return to Sport Following Metacarpal Fractures in Major League Baseball Players
Authors: Pagani Nicholas R. , Sudah Suleiman Y. , Moverman Michael A. , Puzzitiello Richard N. , Menendez Mariano E. , Guss Michael S.
Published: March 2022

Background:

Major League Baseball (MLB) players are at risk for metacarpal fractures; however, little is known regarding the impact of these injuries on future performance. The purpose of this study was to determine whether MLB players who sustain metacarpal fractures demonstrate decreased performance on return to competition in comparison to the performance of control-matched peers.

Methods:

Data for MLB position players with metacarpal fractures incurred over 17 seasons were obtained from injury reports, press releases, and player profiles. Age, position, career experience, body mass index (BMI), injury mechanism, handedness, and treatment were recorded. Individual season statistics for the 2 seasons immediately before injury and the 2 seasons after injury were obtained. Controls matched by player position, age, BMI, career experience, and performance statistics were identified. A performance comparison of the cohorts was performed.

Results:

Overall, 24 players met inclusion criteria. Eleven players with metacarpal fractures were treated with surgery (46%) and 13 (54%) were treated nonoperatively. Players treated nonoperatively missed significantly fewer games following injury compared with those treated operatively (35.5 vs 52.6 games, P = .04). There was no significant difference in postinjury performance when compared with preinjury performance among the fracture cohorts. Players with metacarpal fractures treated nonoperatively had a significant decline in their Wins Above Replacement (WAR) 2 seasons postinjury (1.37 point decline) in comparison to matched controls (0.84 point increase) ( P = .02). There was no significant difference in WAR 1 or 2 seasons postinjury for players with metacarpal fractures treated operatively in comparison to the control cohort.

Conclusions:

Major League Baseball players sustaining metacarpal fractures can expect to return to their preinjury performance levels following both nonoperative and operative treatment. However, players treated nonoperatively may witness a decline in their performance compared with peers over the long term. Orthopedic surgeons treating professional athletes with metacarpal fractures should consider these outcomes when counseling their patients and making treatment recommendations.
Political Skill and Career Success: Exploring the Mediating Role of Mentoring and Moderating Role of Career Adaptability
Authors: Usman Muhammad , Anwar ul Haq Muhammad , Ahmad Shabir , Hussain Jawad , Ali Zahid , Hussain Altaf
Published: March 2022

What determines success in academia? Both researchers and academics have disagreements regarding the notion of success and its determinants in academia. The aim of this paper is to investigate the impact of political skill on employees’ subjective career success and the mediating and moderating role of mentoring and career adaptability in the said relationship respectively. The hypothesized relationships were tested utilizing a representative stratified random sample of 362 faculty members employed in the public sector universities of Pakistan. Results revealed that political skill positively influences subjective career success. The mediation model was supported and as expected: mentoring mediated the link between political skill and career success. The moderated relationship between mentoring and career success was stronger for individuals with higher career adaptability. The study adds to the understanding of underlying mechanisms involved in the political skill-career success nexus. Moderating role of career adaptability in the relationship between political skill and subjective career success was also probed, which further adds to the theoretical contribution of the study. The findings suggest that academics must realize that they need to be politically skilled, should be proactive in seeking mentoring relationships and should better equip themselves to cope with the work uncertainties.
Seroprevalence of SARS-CoV-2 Antibodies in Children and Adolescents: Results From a Population-Based Survey in 10 Colombian Cities
Authors: Mercado-Reyes Marcela María , Daza Marcela , Pacheco Angélica , Meneses-Gil María Ximena , Galindo Marisol , Catama Jenssy , Botero Luz Stefany , Muñoz Lyda , Quinche German , Ospina Martha Lucía
Published: March 2022

Background. Understanding COVID-19 dynamics in Colombia during the first pandemic year (2020) gives important insights surrounding population’s exposure risk and specific susceptibilities. Seroprevalence studies can aid in having a broader understanding of the disease, offering a more inclusive view of the pandemic’s impact across the population. Methods. A population-based cross-sectional study to assess antibodies against SARS-CoV-2 in 10 Colombian cities was developed between September and December 2020. Cities were grouped according development typology (Robust (RD), Intermediate (ID) and Incipient (InD)). Detection of total antibodies (IgM + IgG) against SARS-CoV-2 was employed. Univariate Odds Ratios (OR) were estimated for antibody results and selected variables. Results. About 3124 children aged between 5 and 17 years were included. Factors related to lower seropositive results were affiliation to the employer-based health insurance in RD and ID cities (OR: 0.579, 95% CI 0.477-0.703, OR: 0.648, 95%CI 0.480-0.874 respectively) and living in a household with adequate access to public services only for ID cities (OR: 0.679. 95% CI 0.491-0.939). Higher seropositivity rates in RD and ID cities were seen in children belonging to the low socioeconomic stratum (RD: OR: 1.758, 95% CI 1.427-2.165; ID: OR: 2.288, 95% CI 1.599-3.275) and living in an overcrowded household (RD: OR: 1.846, 95% CI 1.467-2.323; ID: OR: 2.379, 95% CI 1.769-3.199). Conclusions. Children and adolescents showed substantial impact from the COVID-19 pandemic. Disadvantageous living conditions were found to be significantly related to having a positive SARS-CoV-2 antibody test. These results highlight the need to prioritize vulnerable populations in the context of health emergencies.
A rare case of penile schwannomatosis presenting with painful nocturnal penile tumescence
Authors: Tow Chan Ming , Tang Jonathan , Chun Chan Ming , Chien Joe Lee King
Published: March 2022

Background

Penile schwannoma is a rare tumor. They commonly present as an asymptomatic, painless and slow growing mass. Other presentations include sexual dysfunction, most commonly dyspareunia, followed by erectile dysfunction, abnormal penile curvature or pain with ejaculation.

Case presentation

A 26-year-old male presented atypically with painful nocturnal penile tumescence, along with multiple nodules over the dorsal penis. Excision of multiple penile tumors under general anaesthesia was performed and histopathologic examination revealed benign schwannoma.

Conclusion

Our hypothesis is that the schwannoma lies along the axis of the dorsal penile nerve, and compression of this nerve occurs during his erection causing pain. However, there are limited presentations of painful erections in penile schwannomas, and we hope that future studies can help confirm this theory.
Big data ordination towards intensive care event count cases using fast computing GLLVMS
Authors: Caraka Rezzy Eko , Chen Rung-Ching , Huang Su-Wen , Chiou Shyue-Yow , Gio Prana Ugiana , Pardamean Bens
Published: March 2022

Background

In heart data mining and machine learning, dimension reduction is needed to remove multicollinearity. Meanwhile, it has been proven to improve the interpretation of the parameter model. In addition, dimension reduction can also increase the time of computing in high dimensional data.

Methods

In this paper, we perform high dimensional ordination towards event counts in intensive care hospital for Emergency Department (ED 1), First Intensive Care Unit (ICU1), Second Intensive Care Unit (ICU2), Respiratory Care Intensive Care Unit (RICU), Surgical Intensive Care Unit (SICU), Subacute Respiratory Care Unit (RCC), Trauma and Neurosurgery Intensive Care Unit (TNCU), Neonatal Intensive Care Unit (NICU) which use the Generalized Linear Latent Variable Models (GLLVM’s).

Results

During the analysis, we measure the performance and calculate the time computing of GLLVM by employing variational approximation and Laplace approximation, and compare the different distributions, including Negative Binomial, Poisson, Gaussian, ZIP, and Tweedie, respectively. GLLVMs (Generalized Linear Latent Variable Models), an extended version of GLMs (Generalized Linear Models) with latent variables, have fast computing time. The major challenge in latent variable modelling is that the function $$f\left(\varTheta \right)=\int f\left(u\varTheta \right)h\left(u\right)du$$

f

Θ

=
∫
f

u
Θ

h

u

d
u

is not trivial to solve since the marginal likelihood involves integration over the latent variable u.

Conclusions

In a nutshell, GLLVMs lead as the best performance reaching the variance of 98% comparing other methods. We get the best model negative binomial and Variational approximation, which provides the best accuracy by accuracy value of AIC, AICc, and BIC. In a nutshell, our best model is GLLVM-VA Negative Binomial with AIC 7144.07 and GLLVM-LA Negative Binomial with AIC 6955.922.
Influence of radiation dose and predicted tumor invasion depth on local recurrence after definitive chemoradiotherapy for stage 0–I esophageal squamous cell carcinoma: a propensity score-weighted, retrospective, observational study
Authors: Ikawa Toshiki , Ishihara Ryu , Matsueda Katsunori , Konishi Koji , Yamamoto Sachiko , Morimoto Masahiro , Kanayama Naoyuki , Teshima Teruki
Published: March 2022

Background

The optimal radiation dose for treating non-metastatic superficial esophageal squamous cell carcinoma is unknown. In this retrospective observational study, we investigated the influence of radiation dose and pretreatment endoscopic prediction of tumor invasion depth on local recurrence after definitive chemoradiotherapy in patients with superficial esophageal squamous cell carcinoma.

Methods

We analyzed 134 patients with clinical Tis–T1N0M0 esophageal squamous cell carcinoma who underwent chemoradiotherapy at our institution between 2006 and 2019. Patients were grouped into standard-dose (50.0–50.4 Gy) and high-dose (60.0 Gy) radiotherapy groups. The outcomes of interest were local recurrence and major local recurrence (endoscopically unresectable local recurrent tumors). Kaplan–Meier analysis and the log-rank test were used with propensity score and inverse probability of treatment weighting. Cox proportional hazards analysis was performed to identify predictors of local recurrence and major local recurrence.

Results

The median follow-up times were 52 and 84 months for the standard-dose and high-dose groups, respectively. The adjusted 3-year local recurrence and major local recurrence rates in the standard-dose and high-dose groups were 33.8 and 9.6% (adjusted hazard ratio, 4.00 [95% confidence interval: 1.64–9.73]; adjusted log-rank p = 0.001) and 12.5 and 4.7% (adjusted hazard ratio, 3.13 [95% confidence interval: 0.91–10.81]; adjusted log-rank p = 0.098), respectively. Cox proportional hazards analysis showed that standard-dose radiotherapy and endoscopic findings of deep submucosal invasion are independently associated with local recurrence and major local recurrence.

Conclusions

High-dose radiotherapy is more beneficial for local tumor control than standard-dose radiotherapy in patients with non-metastatic superficial esophageal squamous cell carcinoma. The use of high-dose radiotherapy may merit consideration for tumors with deep submucosal invasion.
Are children on track with their routine immunization schedule in a fragile and protracted conflict state of South Sudan? A community-based cross-sectional study
Authors: Idris Israel Oluwaseyidayo , Tapkigen Janet , Kabutaulaka Germaine , Ayeni Gabriel Omoniyi , Ayomoh Francis Ifeanyi , Obwoya Justin Geno
Published: March 2022

Objectives

The objective of this study was to assess if children aged 0–23 months in a conflict-affected state of South Sudan were on track with their immunization schedule and to identify predisposing factors that affected this study population from being on track with their routine immunization schedule.

Design

Community-based cross-sectional study using a semi-structured questionnaire. The binary outcome of interest was defined as being on or off track with routine vaccination schedule. Multivariable logistic regression was used to analyze for the association between the predisposing factors surveyed and being off track with one’s routine immunization schedule.

Setting

Rural communities in four counties (Rumbek Center, Rumbek North, Rumbek East and Wulu) of the Western Lakes state in South Sudan during January 10, 2020 to June 10, 2020.

Participants

We surveyed 428 children aged 0–23 months and their mothers/caregivers who lived in either of the four counties in the Western Lakes State. Participants were selected using random ballot sampling.

Results

More than three-quarters of the children surveyed (75.5%) were off track with their vaccination schedule. Children with an immunization card had 71% reduced odds of being off track with their immunization (AOR = 0.29; 95% CI 0.10–0.83, p-value = 0.021) compared to children without immunization cards. Children who reside near health facilities and do not require transportation to facilities had 87% reduced odds of being off track with their immunization compared to those who lived far and required transport to facilities. Giving an adequate immunization notice before conducting immunization outreach visits to communities was also associated with reduced odds (AOR = 0.27; 95% CI 0.09–0.78. p-value = 0.016) of children being off track with their immunization.

Conclusion

This study revealed that most children were off track with their vaccination schedule in South Sudan, which is not only influenced by maternal characteristics but mainly by community- and state-level immunization service delivery mechanisms. Policies and interventions to improve child immunization uptake should prioritize these contextual characteristics.
The relationship between motherhood and use of mental health care services among married migrant and non-migrant women: a national register study
Authors: Straiton Melanie , Hollander Anna-Clara , Hynek Kamila Angelika , Liefbroer Aart C. , Hauge Lars Johan
Published: March 2022

Background

Giving birth to one’s first child is a life changing event. Beyond the post-partum period, little is known about the association between becoming a mother and mental disorder among migrant women. This study investigates outpatient mental health (OPMH) service use, a proxy for mental disorder, among married migrant and non-migrant women who become mothers and those who do not.

Methods

Using Norwegian register data, we followed 90,195 married women, aged 18-40 years, with no children at baseline between 2008-2013 to see if becoming a mother was associated with OPMH service use. Data were analysed using discrete time analyses.

Results

We found an interaction between motherhood and migrant category. Married non-migrant mothers, both in the perinatal period and beyond, had lower odds of OPMH use than married non-mothers. There was no association between motherhood and OPMH service use for migrants. However, there was no significant interaction between motherhood and migrant category when we excluded women who had been in Norway less than five years. Among women aged 25-40 years, a stable labour market attachment was associated with lower odds of OPMH use for non-migrants but not migrants, regardless of motherhood status.

Conclusions

The perinatal period is not associated with increased odds of OPMH use and appears to be associated with lower odds for married non-migrant women. Selection effects and barriers to care may explain the lack of difference in OPMH service use that we found across motherhood status and labour market attachment for married migrant women. Married migrant women in general have a lower level of OPMH use than married non-migrants. Married migrant women with less than five years in Norway and those with no/weak labour market attachment may experience the greatest barriers to care. Further research to bridge the gap between need for, and use of, mental health care among migrant women is required.
Tobacco use prevalence and its determinate factor in Ethiopia- finding of the 2016 Ethiopian GATS
Authors: Mengesha Sisay Derso , Teklu Kirubel Tesfaye , Weldetinsae Abel , Serte Melaku Gizaw , Kenea Moa Abate , Dinssa Daniel Abera , Woldegabriel Mesay Getachew , Alemayehu Tsigereda Assefa , Belay Wassihun Melaku
Published: March 2022

Background

Tobacco, one of the risk factors for non-communicable diseases, kills 8 million people each year. Like other sub-Saharan countries, Ethiopia faces the potential challenge of a tobacco epidemic. However, there is no organized data on the prevalence of tobacco use in the country. Therefore, this study aims to determine adult tobacco use in Ethiopia.

Methods

The study was conducted using the WHO and CDC GATS survey methods. Complex survey analysis was used to obtain prevalence and population estimates with 95% confidence intervals. Bivariate regression analyses were employed to examine factors related to tobacco use.

Results

The overall tobacco use percentage was 5.0% [95% CI (3.5, 6.9)], of which 65.8% [95% CI (53.4, 76.3)] only smoked tobacco products; 22.5% [95% CI (15.7, 31.2)] used smokeless tobacco only; and 11.8% [95% CI (6.5, 20.4)] used both smoked and smokeless tobacco products. In 2016, more men adults (8.1%) used tobacco than women did (1.8%). Eight out of eleven states have a higher smoking rate than the national average (3.7%). Gender, employment, age, religion, and marital status are closely linked to current tobacco use (p-value< 0.05). Men adults who are employed, married, and mostly from Muslim society are more likely to use tobacco.

Conclusion

The prevalence of tobacco use is still low in Ethiopia. However, the percentage of female smokers is increasing, and regional governments such as Afar and Gambella have a relatively high prevalence. This calls for the full implementation of tobacco control laws following the WHO MPOWER packages. A tailored tobacco control intervention targeting women, younger age groups, and regions with a high proportion of tobacco use are recommended.
No man is an island: management of the emergency response to the SARS-CoV-2 (COVID-19) outbreak in a large public decentralised service delivery organisation
Authors: Ohrling Mikael , Solberg Carlsson Karin , Brommels Mats
Published: March 2022

Background

We wanted to better understand whether and how agility can be achieved in a decentralised service delivery organisation in Sweden. The pandemic outbreak of SARS-Cov-2 (Covid-19) provided an opportunity to assess decentralisation as a strategy to improve the responsiveness of healthcare and at the same time handle an unpredictable and unexpected event.

Methods

Data from in-depth interviews with a crisis management team (n = 23) and free text answers in a weekly survey to subordinated clinical directors, i.e. unit managers, (n = 108) were scrutinised in a directed content analysis. Dynamic capabilities as a prerequisite for dynamic effectiveness, understood as reaching strategic and operative effectiveness simultaneously, were explored by using three frameworks for dynamic effectiveness, dynamic capabilities and delegated authority in a decentralised organisation.

Results

Unpredictable events, such as the pandemic Covid-19 outbreak, demand a high grade of ability to be flexible. We find that a high degree of operational effectiveness, which is imperative in an emergency situation, also is a driver of seeking new strategic positions to even better meet new demands. The characteristics of the dynamic capabilities evolving from this process are described and discussed in relation to decentralisation, defined by decision space, organisational and individual capacity as well as accountability. We present arguments supporting that a decentralised management model can facilitate the agility required in an emergency.

Conclusions

This study is, to our knowledge, the first of its kind where a decentralised management model in a service delivery organisation in healthcare is studied in relation to crisis management. Although stemming from one organisation, our findings indicating the value of decentralisation in situations of crisis are corroborated by theory, suggesting that they could be relevant in other organisational settings also.
Comparison of tumor and two types of paratumoral tissues highlighted epigenetic regulation of transcription during field cancerization in non-small cell lung cancer
Authors: Wang Qiushi , Wu Libo , Yu Jiaxing , Li Guanghua , Zhang Pengfei , Wang Haozhe , Shao Lin , Liu Jinying , Shen Weixi
Published: March 2022

Background

Field cancerization is the process in which a population of normal or pre-malignant cells is affected by oncogenic alterations leading to progressive molecular changes that drive malignant transformation. Aberrant DNA methylation has been implicated in early cancer development in non-small cell lung cancer (NSCLC); however, studies on its role in field cancerization (FC) are limited. This study aims to identify FC-specific methylation patterns that could distinguish between pre-malignant lesions and tumor tissues in NSCLC.

Methods

We enrolled 52 patients with resectable NSCLC and collected resected tumor (TUM), tumor-adjacent (ADJ) and tumor-distant normal (DIS) tissue samples, among whom 36 qualified for subsequent analyses. Methylation levels were profiled by bisulfite sequencing using a custom lung-cancer methylation panel.

Results

ADJ and DIS samples demonstrated similar methylation profiles, which were distinct from distinct from that of TUM. Comparison of TUM and DIS profiles led to identification of 1740 tumor-specific differential methylated regions (DMRs), including 1675 hypermethylated and 65 hypomethylated (adjusted P < 0.05). Six of the top 10 tumor-specific hypermethylated regions were associated with cancer development. We then compared the TUM, ADJ, and DIS to further identify the progressively aggravating aberrant methylations during cancer initiation and early development. A total of 332 DMRs were identified, including a predominant proportion of 312 regions showing stepwise increase in methylation levels as the sample drew nearer to the tumor (i.e. DIS < ADJ < TUM) and 20 regions showing a stepwise decrease pattern. Gene set enrichment analysis (GSEA) for KEGG and GO terms consistently suggested enrichment of DMRs located in transcription factor genes, suggesting a central role of epigenetic regulation of transcription factors in FC and tumorigenesis.

Conclusion

We revealed distinct methylation patterns between pre-malignant lesions and malignant tumors, suggesting the essential role of DNA methylation as an early step in pre-malignant field defects. Moreover, our study also identified differentially methylated genes, especially transcription factors, that could potentially be used as markers for lung cancer screening and for mechanistic studies of FC and early cancer development.
Roles of sirtuin family members in chronic obstructive pulmonary disease
Authors: Zhang Xi-Yue , Li Wei , Zhang Jin-Rong , Li Chun-Yan , Zhang Jie , Lv Xue-Jiao
Published: March 2022

The globally increasing annual incidence of chronic obstructive pulmonary disease (COPD), a common chronic disease, poses a serious risk to public health. Although the exact mechanism underlying the pathogenesis of COPD remains unclear, a large number of studies have shown that its pathophysiology and disease course are closely related to oxidative stress, inflammation, apoptosis, autophagy, and aging. The key players involved in COPD include the sirtuin family of NAD-dependent deacetylases that comprise seven members (SIRT1–7) in mammals. Sirtuins play an important role in metabolic diseases, cell cycle control, proliferation, apoptosis, and senescence. Owing to differences in subcellular localization, sirtuins exhibit anisotropy. In this narrative review, we discuss the roles and molecular pathways of each member of the sirtuin family involved in COPD to provide novel insights into the prevention and treatment of COPD and how sirtuins may serve as adjuvants for COPD treatment.
Hybrid single staged treatment of coronary arteries and aorto-iliac obstruction disease: a case report
Authors: Kasama Keiichiro , Uranaka Yasuko , Tomita Hiroto , Matsumoto Atsushi , Suzuki Shinichi
Published: March 2022

Background

If the internal thoracic artery is a collateral circulation to the lower extremities, careful consideration should be given to its use when coronary artery bypass grafting is required. We report a case of CABG with bilateral common iliac artery lesions and collateral circulation from the bilateral ITAs on the peripheral side.

Case presentation

A 58-year-old man was admitted to our department with claudication and dyspnea upon exertion. He was diagnosed with right common iliac artery obstruction and 90% stenosis of the left common iliac artery. Coronary angiography revealed three-vessel disease with 50% stenosis of the left main trunk. The bilateral ITA showed a rich collateral flow to the lower extremities. Hybrid single staged repair with percutaneous transluminal angioplasty for the left iliac lesion was performed, followed by off-pump coronary artery bypass grafting (CABG) and femoro-femoral crossover bypass. Postoperative angiography revealed that all grafts were patent. The postoperative course was uneventful, except that the patient’s creatinine kinase level increased to 7177 U/L on postoperative day 1.

Conclusion

To treat coronary artery disease with peripheral artery disease, especially those with iliac artery occlusion lesions with collateral circulation from the ITA, not only graft selection but also the treatment strategies for peripheral lesions are considered extremely important. Hybrid single staged coronary and lower limb artery revascularization could be safely achieved by multidisciplinary team strategies.
Reductive TCA cycle catalyzed by wild-type IDH2 promotes acute myeloid leukemia and is a metabolic vulnerability for potential targeted therapy
Authors: Zeng Peiting , Lu Wenhua , Tian Jingyu , Qiao Shuang , Li Jiangjiang , Glorieux Christophe , Wen Shijun , Zhang Hui , Li Yiqing , Huang Peng
Published: March 2022

Background

Isocitrate dehydrogenase-2 (IDH2) is a mitochondrial enzyme that catalyzes the metabolic conversion between isocitrate and alpha-ketoglutarate (α-KG) in the TCA cycle. IDH2 mutation is an oncogenic event in acute myeloid leukemia (AML) due to the generation of 2-hydroxyglutarate. However, the role of wild-type IDH2 in AML remains unknown, despite patients with it suffer worse clinical outcome than those harboring mutant type.

Methods

IDH2 expression in AML cell lines and patient samples was evaluated by RT-qPCR, western blotting and database analyses. The role of wild-type IDH2 in AML cell survival and proliferation was tested using genetic knockdown and pharmacological inhibition in AML cells and animal models. LC–MS, GC–MS, isotope metabolic tracing, and molecular analyses were performed to reveal the underlying mechanisms.

Results

We found that wild-type IDH2 was overexpressed in AML and played a major role in promoting leukemia cell survival and proliferation in vitro and in vivo. Metabolomic analyses revealed an active IDH2-mediated reductive TCA cycle that promoted the conversion of α-KG to isocitrate/citrate to facilitate glutamine utilization for lipid synthesis in AML cells. Suppression of wild-type IDH2 by shRNA resulted in elevated α-KG and decreased isocitrate/citrate, leading to reduced lipid synthesis, a significant decrease in c-Myc downregulated by α-KG, and an inhibition of AML viability and proliferation. Importantly, pharmacological inhibition of IDH2 showed significant therapeutic effect in mice inoculated with AML cells with wt-IDH2 and induced a downregulation of C-MYC in vivo.

Conclusions

Wt-IDH2 is an essential molecule for AML cell survival and proliferation by promoting conversion of α-KG to isocitrate for lipid synthesis and by upregulating c-Myc expression and could be a potential therapeutic target in AML.
Association of recurrent mutations in BRCA1, BRCA2, RAD51C, PALB2, and CHEK2 with the risk of borderline ovarian tumor
Authors: Ogrodniczak Alicja , Menkiszak Janusz , Gronwald Jacek , Tomiczek-Szwiec Joanna , Szwiec Marek , Cybulski Cezary , Dębniak Tadeusz , Huzarski Tomasz , Tołoczko-Grabarek Aleksandra , Byrski Tomasz , Białkowska Katarzyna , Prajzendanc Karolina , Baszuk Piotr , Lubiński Jan , Jakubowska Anna
Published: March 2022

Background

There are several genes associated with ovarian cancer risk. Molecular changes in borderline ovarian tumor (BOT) indicate linkage of this disease to type I ovarian tumors (low-grade ovarian carcinomas). This study determined the prevalence and association of mutations in BRCA1, BRCA2, PALB2, RAD51C, and CHEK2 with the risk of BOTs.

Methods

The study group consisted of 102 patients with histologically confirmed BOT and 1743 healthy controls. In addition, 167 cases with ovarian cancer G1 were analyzed. The analyses included genotyping of 21 founder and recurrent mutations localized in 5 genes (BRCA1, BRCA2, PALB2, RAD51C, and CHEK2). The risk for developing BOT and low-grade ovarian cancer, as well as the association of tested mutations with survival, was estimated.

Results

The CHEK2 missense mutation (c.470T>C) was associated with 2-times increased risk of BOT (OR=2.05, p=0.03), at an earlier age at diagnosis and about 10% worse rate of a 10-year survival. Mutations in BRCA1 and PALB2 were associated with a high risk of ovarian cancer G1 (OR=8.53, p=0.005 and OR=7.03, p=0.03, respectively) and were related to worse all-cause survival for BRCA1 carriers (HR=4.73, 95%CI 1.45–15.43, p=0.01).

Conclusions

Results suggest that CHEK2 (c.470T>C) may possibly play a role in the pathogenesis of BOT, but due to the low number of BOT patients, obtained results should be considered as preliminary. Larger more in-depth studies are required.
Phosphorylation regulation of cardiac proteins in Babesia microti infected mice in an effort to restore heart function
Authors: Yang Xiaohong , Wang Ningmei , Ren Shuguang , Hu Yuhong , Wang Han , Ji Aimeng , Cao Lihui , Li Mengxue , Liu Jingze , Wang Hui
Published: March 2022

Background

Babesia is a common protozoan parasite that infects red blood cells. In mice infected with Babesia microti, the red blood cells were lysed, resulting in decreased oxygen-carrying capacity. To compensate for low blood oxygen levels, stress on the heart was greatly increased. Babesiosis induces a variety of pathologies; meanwhile, heart tissues initiate self-repair responses to babesiosis-induced tissue damage to restore heart function.

Methods

To discover the molecular mechanisms of the damage and self-repair in the heart after B. microti infection in mice, we investigated the changes in protein expression and phosphorylation modification levels in heart tissues at 0, 5, 8, 11, and 19 days post-infection using data-independent acquisition (DIA) quantitative proteomics.

Results

The numbers of global proteins we identified were 1934, 1966, 1984, 1989, and 1955 and of phosphopeptides were 5118, 5133, 5130, 5133, and 5140 at 0, 5, 8, 11, and 19 days, respectively, in heart cells after infection with B. microti. The results showed that after B. microti infection the differentially expressed proteins in mice mainly include fibrinogen α (Fgα), fibrinogen β (Fgβ), Serpina1b, Serpina1c, cathepsin Z, cytochrome c oxidases (COXs), RPS11, and RPS20. The proteins with phosphorylation changes mainly include 20-kDa light chain of myosin II (MLC20), myosin light chain kinase (MLCK), mitogen-activated protein kinase 14 (MAPK14), and Akt1. These proteins were mainly involved in coagulation processes, cell apoptosis, oxidative phosphorylation, and ribosomes.

Conclusions

The coagulation cascade-related proteins, apoptosis-related proteins, oxidative phosphorylation-related proteins, and other types of proteins are all involved in the damage and self-repair process in the heart after B. microti infection. These results offer a wealth of new targets for further exploration into the causes of heart disease induced by Babesia infection and are of great significance for novel drug development and new opportunities for targeted therapies.

Graphical Abstract
Glucose-6-Phosphate dehydrogenase deficiency associated hemolysis in a cohort of new onset type 1 diabetes children in Guangdong province, China
Authors: Xu Aijing , Jiang Minyan , Zhang Wen , Lin Yunting , Shao Yongxian , Mei Huifen , Cheng Jing , Liang Cuili , Li Cuiling , Li Xiuzhen , Liu Li
Published: March 2022

Background

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common human genetic abnormalities, with a high prevalence in Guangdong, China. The purpose of this study was to explore the characteristics of newly diagnosed type 1 diabetes (T1D) patients with G6PD deficiency in a cohort of Chinese children and to investigate the relationship between the diabetic ketoacidosis (DKA) and hemolysis due to G6PD deficiency in these patients.

Methods

A total of 503 newly diagnosed T1D children aged 6 months–18 years were collected and their G6PD enzyme activity were measured. Fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), andG6PDgene were analysed. The pH, HCO3, and plasma osmotic pressure between DKA patients with and without hemolysis at the presentation were compared.

Results

In the present study, G6PD deficiency accounted for 5.3% of newly diagnosed T1D children. There were no significant differences in FPG/HbA1c and HbA1c levels between T1D children alone and T1D children with G6PD deficiency. Hemolysis appeared in five of the twenty-two DKA patients with G6PD deficiency. Two patients had fever at onset and were given ibuprofen and cefazolin. The other three patients did not have infection or ingestion of hemolytic drugs. There were no significant difference in pH, HCO3, and osmotic pressure between the children with DKA with and without hemolysis at the presentation. The hemolysis occurred between 2 and 7 days after admission and the hyperglycaemia had been corrected by the time hemolysis occurs. FourG6PDgene mutations were found in the diabetes with G6PD deficiency patients: c.1376G > T, c.1388G > A, c.95A > G, and c.871G > A, all of which were genes with high frequency of G6PD deficiency in Guangdong Province. No correlation between genotype and hemolysis was found.

Conclusion

In the present study, we found the frequency of G6PD deficiency among newly diagnosed T1D children was similar to that of the general population. However, DKA children with G6PD deficiency are prone to occur hemolytic anemia, and these hemolysis usually occurs when DKA is corrected and blood glucose is in homeostatic state, which is easy to be ignored. To reduce the risk of this complication, especially in areas with high incidence of G6PD deficiency, screening for G6PD activity in people with newly diagnosed diabetes should be considered.
Musculoskeletal pain and its association with health status, maturity, and sports performance in adolescent sport school students: a 2-year follow-up
Authors: Malmborg Julia S. , Bremander Ann , Bergman Stefan , Haglund Emma , Olsson M. Charlotte
Published: March 2022

Background

Musculoskeletal pain and its risk factors are rarely assessed in studies on adolescent athletes. The aim was to identify risk factors at baseline that were associated with the persistence or development of musculoskeletal pain at a two-year follow-up in adolescent sport school students, and to study cross-sectional associations at follow-up between musculoskeletal pain and sports performance.

Methods

Sport school students (79 boys and 52 girls, aged 14 years at baseline) were divided into infrequent (never–monthly) or frequent (weekly–almost daily) pain groups, based on frequency of pain using a pain mannequin. Logistic regression analyses were performed to study longitudinal associations between frequent pain at follow-up and baseline variables: pain group, number of regions with frequent pain, health status by EQ-5D, maturity offset (pre, average, or post peak height velocity), and sports (contact or non-contact). Linear regression analyses were used to study cross-sectional associations between pain groups and 20-m sprint, agility T-test, counter-movement jump, and grip strength at follow-up. Results were stratified by sex.

Results

A higher percentage of girls than boys reported frequent pain at follow-up (62% vs. 37%; p = 0.005). In boys, frequent pain at follow-up was associated with being pre peak height velocity at baseline (OR 3.884, CI 1.146–13.171; p = 0.029) and participating in non-contact sports (OR 3.429, CI 1.001–11.748; p = 0.050). In girls, frequent pain at follow-up was associated with having frequent pain in two or more body regions at baseline (OR 3.600, CI 1.033–12.542; p = 0.044), having a worse health status at baseline (OR 3.571, CI 1.026–12.434; p = 0.045), and participating in non-contact sports (OR 8.282, CI 2.011–34.116; p = 0.003). In boys, frequent pain was associated with worse performances in 20-m sprint and counter-movement jump, but not in agility T-test and grip strength.

Conclusions

Baseline risk factors for having frequent pain at follow-up were late maturation in boys, frequent pain and worse health status in girls, and participation in non-contact sports in both sexes. Boys with pain performed worse in sports tests. Coaches and school health-care services should pay attention to the risk factors and work towards preventing pain from becoming persistent.
The Autism Biomarkers Consortium for Clinical Trials: evaluation of a battery of candidate eye-tracking biomarkers for use in autism clinical trials
Authors: Shic Frederick , Naples Adam J. , Barney Erin C. , Chang Shou An , Li Beibin , McAllister Takumi , Kim Minah , Dommer Kelsey J. , Hasselmo Simone , Atyabi Adham , Wang Quan , Helleman Gerhard , Levin April R. , Seow Helen , Bernier Raphael , Charwaska Katarzyna , Dawson Geraldine , Dziura James , Faja Susan , Jeste Shafali Spurling , Johnson Scott P. , Murias Michael , Nelson Charles A. , Sabatos-DeVito Maura , Senturk Damla , Sugar Catherine A. , Webb Sara J. , McPartland James C.
Published: March 2022

Background

Eye tracking (ET) is a powerful methodology for studying attentional processes through quantification of eye movements. The precision, usability, and cost-effectiveness of ET render it a promising platform for developing biomarkers for use in clinical trials for autism spectrum disorder (ASD).

Methods

The Autism Biomarkers Consortium for Clinical Trials conducted a multisite, observational study of 6–11-year-old children with ASD (n = 280) and typical development (TD, n = 119). The ET battery included: Activity Monitoring, Social Interactive, Static Social Scenes, Biological Motion Preference, and Pupillary Light Reflex tasks. A priori, gaze to faces in Activity Monitoring, Social Interactive, and Static Social Scenes tasks were aggregated into an Oculomotor Index of Gaze to Human Faces (OMI) as the primary outcome measure. This work reports on fundamental biomarker properties (data acquisition rates, construct validity, six-week stability, group discrimination, and clinical relationships) derived from these assays that serve as a base for subsequent development of clinical trial biomarker applications.

Results

All tasks exhibited excellent acquisition rates, met expectations for construct validity, had moderate or high six-week stabilities, and highlighted subsets of the ASD group with distinct biomarker performance. Within ASD, higher OMI was associated with increased memory for faces, decreased autism symptom severity, and higher verbal IQ and pragmatic communication skills.

Limitations

No specific interventions were administered in this study, limiting information about how ET biomarkers track or predict outcomes in response to treatment. This study did not consider co-occurrence of psychiatric conditions nor specificity in comparison with non-ASD special populations, therefore limiting our understanding of the applicability of outcomes to specific clinical contexts-of-use. Research-grade protocols and equipment were used; further studies are needed to explore deployment in less standardized contexts.

Conclusions

All ET tasks met expectations regarding biomarker properties, with strongest performance for tasks associated with attention to human faces and weakest performance associated with biological motion preference. Based on these data, the OMI has been accepted to the FDA’s Biomarker Qualification program, providing a path for advancing efforts to develop biomarkers for use in clinical trials.
Thyroid hormone enhances stem cell maintenance and promotes lineage-specific differentiation in human embryonic stem cells
Authors: Deng Chunhao , Zhang Zhaoying , Xu Faxiang , Xu Jiaqi , Ren Zhili , Godoy-Parejo Carlos , Xiao Xia , Liu Weiwei , Zhou Zhou , Chen Guokai
Published: March 2022

Background

Thyroid hormone triiodothyronine (T3) is essential for embryogenesis and is commonly used during in vitro fertilization to ensure successful implantation. However, the regulatory mechanisms of T3 during early embryogenesis are largely unknown.

Method

To study the impact of T3 on hPSCs, cell survival and growth were evaluated by measurement of cell growth curve, cloning efficiency, survival after passaging, cell apoptosis, and cell cycle status. Pluripotency was evaluated by RT-qPCR, immunostaining and FACS analysis of pluripotency markers. Metabolic status was analyzed using LC–MS/MS and Seahorse XF Cell Mito Stress Test. Global gene expression was analyzed using RNA-seq. To study the impact of T3 on lineage-specific differentiation, cells were subjected to T3 treatment during differentiation, and the outcome was evaluated using RT-qPCR, immunostaining and FACS analysis of lineage-specific markers.

Results

In this report, we use human pluripotent stem cells (hPSCs) to show that T3 is beneficial for stem cell maintenance and promotes trophoblast differentiation. T3 enhances culture consistency by improving cell survival and passaging efficiency. It also modulates cellular metabolism and promotes energy production through oxidative phosphorylation. T3 helps maintain pluripotency by promoting ERK and SMAD2 signaling and reduces FGF2 dependence in chemically defined culture. Under BMP4 induction, T3 significantly enhances trophoblast differentiation.

Conclusion

In summary, our study reveals the impact of T3 on stem cell culture through signal transduction and metabolism and highlights its potential role in improving stem cell applications.
Exendin-4 and eldecalcitol synergistically promote osteogenic differentiation of bone marrow mesenchymal stem cells through M2 macrophages polarization via PI3K/AKT pathway
Authors: Lu Yupu , Liu Shanshan , Yang Panpan , Kou Yuying , Li Congshan , Liu Hongrui , Li Minqi
Published: March 2022

Background

The incidence of diabetic osteoporosis is increasing. This article evaluates the effect of combination treatment with the hypoglycemic drug exendin-4 (Ex-4) and the vitamin D analog eldecalcitol (ED-71) on improving diabetic osteoporosis and explores the relevant mechanism of action.

Method

Micro-CT, HE staining, immunohistochemistry, qPCR and ELISA were used to evaluate the impact of Ex-4 and ED-71 on bone formation and macrophage polarization in a mouse model of diabetic osteoporosis in vivo. Immunofluorescence, flow cytometry and qPCR were used to characterize the polarization type of macrophages treated with Ex-4 and ED-71 in vitro. A co-culture system of BMSCs and macrophages was established. Subsequently, crystal violet staining, alkaline phosphatase staining and alizarin red staining were used to evaluate the migration and osteogenesis differentiation of BMSCs.

Results

Ex-4 combined with ED-71 significantly reduced blood glucose levels and enhanced bone formation in mice with diabetic osteoporosis. In addition, Ex-4 synergized with ED-71 to induce the polarization of macrophages into M2 through the PI3K/AKT pathway. Macrophages treated with the combination of Ex-4 and ED-71 can significantly induce the osteogenic differentiation of BMSCs.

Conclusion

Ex-4 synergized with ED-71 to reduce blood glucose levels significantly. And this combination therapy can synergistically induce osteogenic differentiation of BMSCs by promoting M2 macrophages polarization, thereby improving diabetic osteoporosis. Therefore, the combination of Ex-4 and ED-71 may be a new strategy for the treatment of diabetic osteoporosis.
StemSC: a cross-dataset human stemness index for single-cell samples
Authors: Zheng Hailong , Xie Jiajing , Song Kai , Yang Jing , Xiao Huiting , Zhang Jiashuai , Li Keru , Yuan Rongqiang , Zhao Yuting , Gu Yunyan , Zhao Wenyuan
Published: March 2022

Background

Stemness is defined as the potential of cells for self-renewal and differentiation. Many transcriptome-based methods for stemness evaluation have been proposed. However, all these methods showed low negative correlations with differentiation time and can’t leverage the existing experimentally validated stem cells to recognize the stem-like cells.

Methods

Here, we constructed a stemness index for single-cell samples (StemSC) based on relative expression orderings (REO) of gene pairs. Firstly, we identified the stemness-related genes by selecting the genes significantly related to differentiation time. Then, we used 13 RNA-seq datasets from both the bulk and single-cell embryonic stem cell (ESC) samples to construct the reference REOs. Finally, the StemSC value of a given sample was calculated as the percentage of gene pairs with the same REOs as the ESC samples.

Results

We validated the StemSC by its higher negative correlations with differentiation time in eight normal datasets and its higher positive correlations with tumor dedifferentiation in three colorectal cancer datasets and four glioma datasets. Besides, the robust of StemSC to batch effect enabled us to leverage the existing experimentally validated cancer stem cells to recognize the stem-like cells in other independent tumor datasets. And the recognized stem-like tumor cells had fewer interactions with anti-tumor immune cells. Further survival analysis showed the immunotherapy-treated patients with high stemness had worse survival than those with low stemness.

Conclusions

StemSC is a better stemness index to calculate the stemness across datasets, which can help researchers explore the effect of stemness on other biological processes.