bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic syndrome and its components predict the biochemical recurrence and adverse pathological features of patients following radical prostatectomy: a propensity score matching study
Authors: Liu Zenan , Zhu Xuehua , He Jide , Lu Jian
Published: January 2023

Background

To investigate the predictive value of metabolic syndrome (MetS) and its components in biochemical recurrence (BCR) and adverse pathological features of patients with prostate cancer (PCa) after radical prostatectomy (RP).

Methods

A total of 525 PCa patients who underwent RP between 2010 and 2019 at Peking University Third Hospital were analyzed retrospectively. The Kaplan–Meier method was performed to assess BCR-free survival (BCRFS). Univariate and multivariate Cox regression models and multivariate logistic regression models were conducted to identify the predictive factors of BCRFS and adverse pathological features respectively before and after propensity score matching (PSM).

Results

Enrolled patients were allocated into MetS group (n = 136) and non-MetS group (n = 389) according to the presence or absence of MetS, and 127 new matched pairs were identified to balance the baseline characteristics after 1:1 PSM. In propensity matched patients, the Kaplan–Meier analysis revealed that MetS (P = 0.020), hyperglycemia (P = 0.015) and hypertriglyceridemia (P = 0.001) were significantly associated with worse BCRFS; the results of multivariate Cox analyses showed that hyperglycemia (P = 0.040), hypertriglyceridemia (P = 0.017), percentage of positive biopsy cores (P = 0.041) and prostate specific antigen (P = 0.019) were identified as independent prognostic factors for BCRFS. In addition, hypertriglyceridemia was independently associated with non-organ confined disease (NOCD) (P = 0.010), extra-capsular extension (ECE) (P = 0.010) and upgrading (P = 0.017) in the multivariate logistic analyses.

Conclusions

Hyperglycemia and hypertriglyceridemia are the two effective MetS components both identified as independent risk factors for worse BCRFS after RP, while hypertriglyceridemia was independently associated with NOCD, ECE and upgrading as well.
Noninvasive carbon dioxide monitoring in pediatric patients undergoing laparoscopic surgery: transcutaneous vs. end-tidal techniques
Authors: Wang Weitao , Zhao Zhifa , Tian Xinjie , Ma Xinggang , Xu Liang , Shang Guanglin
Published: January 2023

Purpose

The present study aimed to investigate the correlation between transcutaneous carbon dioxide partial pressure (PtcCO2) and arterial carbon dioxide pressure (PaCO2) and the accuracy of PtcCO2 in predicting PaCO2 during laparoscopic surgery in pediatric patients.

Methods

Children aged 2–8 years with American Society of Anesthesiologists (ASA) class I or II who underwent laparoscopic surgery under general anesthesia were selected. After anesthesia induction and tracheal intubation, PtcCO2 was monitored, and radial arterial catheterization was performed for continuous pressure measurement. PaCO2, PtcCO2, and end-tidal carbon dioxide partial pressure (PetCO2) were measured before pneumoperitoneum, and 30, 60, and 90 min after pneumoperitoneum, respectively. The correlation and agreement between PtcCO2 and PaCO2, PetCO2, and PaCO2 were evaluated.

Results

A total of 32 patients were eventually enrolled in this study, resulting in 128 datasets. The linear regression equations were: PtcCO2 = 7.89 + 0.82 × PaCO2 (r2 = 0.70, P < 0.01); PetCO2 = 9.87 + 0.64 × PaCO2 (r2 = 0.69, P < 0.01). The 95% limits of agreement (LOA) of PtcCO2 – PaCO2 average was 0.66 ± 4.92 mmHg, and the 95% LOA of PetCO2 – PaCO2 average was –4.4 ± 4.86 mmHg. A difference of ≤ 5 mmHg was noted between PtcCO2 and PaCO2 in 122/128 samples and between PetCO2 and PaCO2 in 81/128 samples (P < 0.01).

Conclusion

In pediatric laparoscopic surgery, a close correlation was established between PtcCO2 and PaCO2. Compared to PetCO2, PtcCO2 can estimate PaCO2 accurately and could be used as an auxiliary monitoring indicator to optimize anesthesia management for laparoscopic surgery in children; however, it is not a substitute for PetCO2.

Registration number of Chinese Clinical Trial Registry

ChiCTR2100043636.
Factors affecting outdoor physical activity in extreme temperatures in a sub-tropical Chinese urban population: an exploratory telephone survey
Authors: Ho Janice Y. , Lam Holly Y. C. , Huang Zhe , Liu Sida , Goggins William B. , Mo Phoenix K. H. , Chan Emily Y. Y.
Published: January 2023

Background

Physical activity (PA) can be affected by extreme temperatures, however fewer studies have identified factors impacting this relationship. This study sought to identify factors associated with changes of outdoor PA during extreme cold/heat events in a sub-tropical Chinese urban population, including factors of sociodemographic, health conditions, temperature-related awareness and attitude, and protective behaviours.

Methods

Two telephone surveys were conducted a week after extreme cold/heat events in 2016 and 2017 among a cohort of Hong Kong residents over age 15. Data was collected on self-reported changes in outdoor PA level during the periods of extreme temperatures, health status, comorbidities, sociodemographic, and temperature-related awareness, and behavioural variables. We conducted multivariable logistic regression analyses to assess predictors of change in outdoor PA over the two extreme temperature events.

Results and Conclusion: Among 435 participants (42.8% response rate), over a third of the participants reported decreased outdoor PA level in extreme temperature events, while 10% reported an increase in extreme heat. Self-reported cardiovascular diseases were associated with decreased PA level in extreme cold, while hypertension was associated with unchanged/increased PA level in extreme heat. These results suggest physical activity to be an important consideration in the understanding of climate change-and-health pathways and meriting further research.
Effects of cleaning spray use on eyes, airways, and ergonomic load
Authors: Lovén Karin , Gudmundsson Anders , Assarsson Eva , Kåredal Monica , Wierzbicka Aneta , Dahlqvist Camilla , Nordander Catarina , Xu Yiyi , Isaxon Christina
Published: January 2023

Background

Cleaning workers are exposed to chemicals and high physical workload, commonly resulting in airway problems and pain. In this study the response in the upper airways and the physical workload following airborne and ergonomic exposure of cleaning spray was investigated.

Methods

A survey was answered by professional cleaning workers to investigate their use of cleaning sprays and the perceived effects on eyes, airways and musculoskeletal pain. A human chamber exposure study was then conducted with 11 professional cleaning workers and 8 non-professional cleaning workers to investigate the airborne exposure, acute effects on eyes and airways, and physical load during cleaning with sprays, foam application and microfiber cloths premoistened with water. All cleaning products used were bleach, chlorine, and ammonia free. The medical assessment included eye and airway parameters, inflammatory markers in blood and nasal lavage, as well as technical recordings of the physical workload.

Results

A high frequency of spray use (77%) was found among the 225 professional cleaning workers that answered the survey. Based on the survey, there was an eight times higher risk (p < 0.001) of self-experienced symptoms (including symptoms in the nose, eyes and throat, coughing or difficulty breathing) when they used sprays compared to when they cleaned with other methods. During the chamber study, when switching from spray to foam, the airborne particle and volatile organic compound (VOC) concentrations showed a decrease by 7 and 2.5 times, respectively. For the whole group, the peak nasal inspiratory flow decreased (-10.9 L/min, p = 0.01) during spray use compared to using only water-premoistened microfiber cloths. These effects were lower during foam use (-4.7 L/min, p = 0.19). The technical recordings showed a high physical workload regardless of cleaning with spray or with water.

Conclusion

Switching from a spraying to a foaming nozzle decreases the exposure of both airborne particles and VOCs, and thereby reduces eye and airway effects, and does not increase the ergonomic load. If the use of cleaning products tested in this study, i.e. bleach, chlorine, and ammonia free, cannot be avoided, foam application is preferable to spray application to improve the occupational environment.
Toward a conceptual framework of health and its operational definition: an application in the 1958 British birth cohort
Authors: Joannès Camille , Colineaux Hélène , Guernec Gregory , Castagné Raphaële , Kelly-Irving Michelle
Published: January 2023

Background

Defining and measuring Health presents a challenge, partly due to its conceptual pluralism. To measure Health as an ability to adapt and self-manage, we developed an approach within the theoretical framework of resources and reserves over the life course, recently proposed in the literature. We aimed to (i) use the conceptual framework developed to identify indicators of deteriorating health reserves, (ii) construct an overall health measure from these indicators, (iii) evaluate the association between the overall health measure and subsequent health outcomes and (iv) assess the robustness of our method.

Methods

We used data from 7,043 individuals born in 1958 in Great Britain included in the National Child Development Study. An overall health measure was constructed via the sum of three selected indicators of deteriorating health reserves in mid-life: chronic widespread pain (CWP), Clinical Interview Schedule - revised (CIS-r), and allostatic load (AL). A three-category variable was defined: impaired/medium/optimal overall health. We explored criterion validity by modelling the relationships between the overall health measure, or each reserve taken separately at 44–45 years, and self-rated health at 46 years and mortality up to 58 years, corresponding to 14 years of follow up, using Cox and logistic regressions respectively. We performed comparative analyses to assess the robustness of the method.

Results

Having an impaired overall health measure was significantly associated with all-cause premature mortality (HRimpaired = 2.74 [1.86; 4.05]) and an increased risk of later fair/poor/very poor self-rated health (ORimpaired = 7.50 [6.29; 8.95]). The overall health measure had a greater effect on the self-rated health estimates than each indicator of deteriorating health reserves considered separately (ORAL medium = 1.82 [1.59; 2.09]; ORAL high = 2.74 [2.37; 3.16]; ORCIS-r = 5.20 [4.45; 6.08]; ORCWP = 2.85 [2.53; 3.21]). CIS-r and allostatic load were also associated with premature mortality contrary to chronic widespread pain (HRAL medium1.82 [1.27; 2.61]; HRAL high = 3.10 [2.19; 4.40]; HRCIS-r = 1.77 [1.22; 2.56]; HRCWP = 1.32 [0.98; 1.76]). The multiple comparative analyses conducted allowed us to assess the robustness of our method within this cohort.

Conclusions

We proposed a method for measuring Health in mid-life in line with the concept of Health as the ability to adapt and self-manage and the concept of health reserves. This method may be applied and further developed within the field of social and positive epidemiology.
Geographical variations and district-level factors associated with COVID-19 mortality in Indonesia: a nationwide ecological study
Authors: Surendra Henry , Paramita Danarastri , Arista Nora N. , Putri Annisa I. , Siregar Akbar A. , Puspaningrum Evelyn , Rosylin Leni , Gardera Dida , Girianna Montty , Elyazar Iqbal R. F.
Published: January 2023

Background

Ensuring health equity, especially for vulnerable populations in less developed settings with poor health system is essential for the current and future global health threats. This study examined geographical variations of COVID-19 mortality and its association with population health characteristics, health care capacity in responding pandemic, and socio-economic characteristics across 514 districts in Indonesia.

Methods

This nationwide ecological study included aggregated data of COVID-19 cases and deaths from all 514 districts in Indonesia, recorded in the National COVID-19 Task Force database, during the first two years of the epidemic, from 1 March 2020 to 27 February 2022. The dependent variable was district-level COVID-19 mortality rate per 100,000 populations. The independent variables include district-level COVID-19 incidence rate, population health, health care capacity, and socio-demographics data from government official sources. We used multivariable ordinal logistic regression to examine factors associated with higher mortality rate.

Results

Of total 5,539,333 reported COVID-19 cases, 148,034 (2.7%) died, and 5,391,299 (97.4%) were recovered. The district-level mortality rate ranged from 0 to 284 deaths per 100,000 populations. The top five districts with the highest mortality rate were Balikpapan (284 deaths per 100,000 populations), Semarang (263), Madiun (254), Magelang (250), and Yogyakarta (247). A higher COVID-19 incidence (coefficient 1.64, 95% CI 1.22 to 1.75), a higher proportion of ≥ 60 years old population (coefficient 0.26, 95% CI 0.06 to 0.46), a higher prevalence of diabetes mellitus (coefficient 0.60, 95% CI 0.37 to 0.84), a lower prevalence of obesity (coefficient -0.32, 95% CI -0.56 to -0.08), a lower number of nurses per population (coefficient -0.27, 95% CI -0.50 to -0.04), a higher number of midwives per population (coefficient 0.32, 95% CI 0.13 to 0.50), and a higher expenditure (coefficient 0.34, 95% CI 0.10 to 0.57) was associated with a higher COVID-19 mortality rate.

Conclusion

COVID-19 mortality rate in Indonesia was highly heterogeneous and associated with higher COVID-19 incidence, different prevalence of pre-existing comorbidity, healthcare capacity in responding the pandemic, and socio-economic characteristics. This study revealed the need of controlling both COVID-19 and those known comorbidities, health capacity strengthening, and better resource allocation to ensure optimal health outcomes for vulnerable population.
Fusion rates based on type of bone graft substitute using minimally invasive scoliosis surgery for adolescent idiopathic scoliosis
Authors: Yang Jae Hyuk , Kim Hong Jin , Chang Dong-Gune , Suh Seung Woo
Published: January 2023

Background

Minimally invasive scoliosis surgery (MISS) is currently introduced on novel technique for surgical treatment of adolescent idiopathic scoliosis (AIS). This study is aimed to evaluate the efficacy of facet fusion in MISS compared to posterior fusion in conventional open scoliosis surgery (COSS) and compare facet fusion rates based on three bone graft substitutes in MISS for adolescent idiopathic scoliosis (AIS).

Methods

Eighty six AIS patients who underwent scoliosis surgery were divided into two groups: the COSS group and the MISS group. COSS was performed through posterior fusion with allograft. MISS was applied via facet fusion with three bone graft substitutes. The MISS group was further divided into three subgroups based on graft substitute: Group A (allograft), Group B (demineralized bone matrix [DBM]), and group C (demineralized cancellous bone chips). Fusion rate was measured using conventional radiographs to visualize loss of correction > 10°, presence of lysis around implants, breaks in fusion mass, and abnormal mobility of the fused segment.

Results

The fusion rates showed no significant difference in COSS and MISS groups (p = 0.070). In the MISS group, the fusion rates were 85, 100, and 100% in groups A, B, and C, respectively, with no significant difference (p = 0.221). There were no statistical differences between groups A, B, and C in terms of correction rate, fusion rate, and SRS-22 scores (p > 0.05).

Conclusions

The facet fusion in MISS showed comparable to posterior fusion in COSS with regard to radiological and clinical outcomes. Furthermore, the type of graft substitute among allograft, DBM, and demineralized cancellous bone chips did not affect facet fusion rate or clinical outcomes in MISS. Therefore, MISS showed comparable fusion rate (with no influences on the type of graft substitute) and clinical outcomes to those of COSS in the surgical treatment of AIS.
Risk factors for early and late morbidity in patients with cardiovascular disease undergoing inguinal hernia repair with a tailored approach: a single-center cohort study
Authors: Hajili Kamran , Vega Hernandez Alberto , Otten Jakob , Richards Dana , Rudroff Claudia
Published: January 2023

Background

Inguinal hernia repair is a common procedure in surgery. Patients with cardiovascular disease have an increased operative risk for postoperative morbidity. The study aimed to identify the most beneficial surgical procedure for these patients.

Methods

Patients undergoing elective surgery for unilateral or bilateral inguinal hernia between December 2015 and February 2020 were included. The cohort was divided into the group of patients with (CVD group) and without (NO group) cardiovascular disease and analyzed according to the postoperative morbidity distribution and correlated to the surgical technique used.

Results

Of the 474 patients included 223 (47%) were operated on using the Lichtenstein technique and 251 (53%) using TAPP, respectively. In the CVD group the Lichtenstein procedure was more common (n = 102, 68.9%), in the NO group it was TAPP (n = 205, 62.9%; p < 0.001). 13 (8.8%) patients in the CVD group and 12 (3.7%) patients in the NO group developed a postoperative hematoma (p = 0.023). In the further subgroup analysis within the CVD group revealed cumarine treatment as a risk factor for postoperative hematoma development, whereas the laparoscopic approach did not elevate the morbidity risk.

Conclusion

CVD is a known risk factor for perioperative morbidity in general surgery, however, the TAPP method does not elevate the individual perioperative risk.
Evaluation of delphinidin as a storage medium for avulsed teeth
Authors: Nam Ok Hyung , Ro Sang Tae , Lee Hyeon-Woo , Jeong Jaeki , Chae Yong Kwon , Lee Ko Eun , Choi Sung Chul , Kang Sang Wook
Published: January 2023

Background

Delphinidin (DP), an anthocyanidin found in blueberries, has antioxidant and anti-inflammatory effects. This study aimed to investigate the efficacy of DP as a storage medium for avulsed teeth.

Methods

Human periodontal ligament cells were cultured and exposed to DP solution (10, 50, and 100 μM), Dulbecco’s modified Eagle’s medium, Hank’s balanced salt solution and tap water. Cell counting kit-8 assays were performed after 0.5, 1, 6, and 24 h to measure the cell viability. Nitric oxide assays and gelatin zymography were performed to evaluate the anti-inflammatory effects of DP. Reverse transcription-polymerase chain reaction was used to determine the expression levels of inflammatory cytokines.

Results

The viability of periodontal ligament cells was greatest at 100 μM DP. At 1 h, 100 μM DP decreased nitric oxide synthesis (p < .0167). Matrix metallopeptidase-9 activity was inhibited by DP in a dose-dependent manner (p < .0167). Moreover, treatment with 100 μM DP decreased the expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8 in periodontal ligament cells (p < .0167).

Conclusions

Within the limits of this study, DP preserved the viability and suppressed the inflammatory response of periodontal ligament cells. These findings suggest that DP could be promising for preservation of avulsed teeth.
Understanding the barriers and enablers for postgraduate medical trainees becoming simulation educators: a qualitative study
Authors: Muhumuza Albert , Najjuma Josephine Nambi , MacIntosh Heather , Sharma Nishan , Singhal Nalini , Hollaar Gwendolyn L , Wishart Ian , Bajunirwe Francis , Santorino Data
Published: January 2023

Introduction 

There is increasing evidence that Simulation-based learning (SBL) is an effective teaching method for healthcare professionals. However, SBL requires a large number of faculty to facilitate small group sessions. Like many other African contexts, Mbarara University of Science and Technology (MUST) in Uganda has large numbers of medical students, but limited resources, including limited simulation trained teaching faculty. Postgraduate medical trainees (PGs) are often involved in clinical teaching of undergraduates. To establish sustainable SBL in undergraduate medical education (UME), the support of PGs is crucial, making it critical to understand the enablers and barriers of PGs to become simulation educators.

Methods

We used purposive sampling and conducted in-depth interviews (IDIs) with the PGs, key informant interviews (KIIs) with university staff, and focus group discussions (FGDs) with the PGs in groups of 5–10 participants. Data collection tools were developed using the Consolidated framework for implementation research (CFIR) tool. Data were analyzed using the rigorous and accelerated data reduction (RADaR) technique.

Results

We conducted seven IDIs, seven KIIs and four focus group discussions. The barriers identified included: competing time demands, negative attitude towards transferability of simulation learning, inadequacy of medical simulation equipment, and that medical simulation facilitation is not integrated in the PGs curriculum. The enablers included: perceived benefits of medical simulation to medical students plus PGs and in-practice health personnel, favorable departmental attitude, enthusiasm of PGs to be simulation educators, and improved awareness of the duties of a simulation educator. Participants recommended sensitization of key stakeholders to simulation, training and motivation of PG educators, and evaluation of the impact of a medical simulation program that involves PGs as educators.

Conclusion

In the context of a low resource setting with large undergraduate classes and limited faculty members, SBL can assist in clinical skill acquisition. Training of PGs as simulation educators should address perceived barriers and integration of SBL into UME. Involvement of departmental leadership and obtaining their approval is critical in the involvement of PGs as simulation educators.
Brief diesel exhaust exposure acutely impairs functional brain connectivity in humans: a randomized controlled crossover study
Authors: Gawryluk Jodie R. , Palombo Daniela J. , Curran Jason , Parker Ashleigh , Carlsten Chris
Published: January 2023

Background

While it is known that exposure to traffic-related air pollution causes an enormous global toll on human health, neurobiological underpinnings therein remain elusive. The study addresses this gap in knowledge.

Methods

We performed the first controlled human exposure study using functional MRI with an efficient order-randomized double-blind crossover study of diesel exhaust (DE) and control (filtered air; FA) in 25 healthy adults (14 males, 11 females; 19–49 years old; no withdrawals). Analyses were carried out using a mixed effects model in FLAME. Z (Gaussianised T/F) statistic images were thresholded non-parametrically using clusters determined by Z > 2.3 and a (corrected) cluster significance threshold of p = 0.05.

Results

All 25 adults went through the exposures and functional MRI imaging were collected. Exposure to DE yielded a decrease in functional connectivity compared to exposure to FA, shown through the comparison of DE and FA in post-exposure measurement of functional connectivity.

Conclusion

We observed short-term pollution-attributable decrements in default mode network functional connectivity. Decrements in brain connectivity causes many detrimental effects to the human body so this finding should guide policy change in air pollution exposure regulation.

Trial registration

University of British Columbia Clinical Research Ethics Board (# H12-03025), Vancouver Coastal Health Ethics Board (# V12-03025), and Health Canada’s Research Ethics Board (# 2012-0040).
Perceptions and experiences of environmental health and risks among Latina mothers in urban Los Angeles, California, USA
Authors: Kamai Elizabeth M. , Calderon Andrea , Van Horne Yoshira Ornelas , Bastain Theresa M. , Breton Carrie V. , Johnston Jill E.
Published: January 2023

Background

Environmental exposures during pregnancy and early childhood can have acute and chronic adverse health impacts. As minoritized populations are more likely to reside in areas with greater pollution, it is important to understand their views and lived experiences to inform action. The purpose of this community-driven qualitative research study was to understand how urban Latina mothers in Los Angeles County, California perceived environmental health and risks.

Methods

We conducted semi-structured individual interviews with Latina pregnant women and mothers of young children, recruited through existing collaborations with community organizations. Interviews conducted in either English or Spanish and were coded inductively according to a modified grounded theory approach.

Results

Thirty-six Latina mothers completed interviews between August–October 2016. Participants lived primarily in low-income communities of South-Central Los Angeles and East Los Angeles. We identified three major themes based on the participants’ responses during interviews: Defining the Environment, Environment & Health Risks, and Social & Political Responsibility. Women defined their environment in terms of both “nature” and “hazards.” They consistently identified foul odors, dirtiness, noise, trash, bugs, smoke, and other visible blights as indicators of household and neighborhood environmental hazards. They expressed fear and uncertainty about how their environment could affect their health and that of their children, as well as specific concerns about respiratory health, asthma, allergies, cancer, and adverse pregnancy outcomes. Mothers often changed individual behaviors around diet and cleaning during pregnancy but were frustrated by power imbalances that left them unable to change their home or neighborhood environments, despite their desire to do so.

Discussion

Our study is among the first to describe how urban Latina mothers perceive and experience environmental health risks during pregnancy and early childhood. Our research suggests additional attention is needed by public health professionals and researchers to address the environmental health risks that matter most to urban Latina mothers. They also highlight the tension that many urban Latina mothers feel between wanting to protect their families’ health and well-being and feeling powerless to change their environment. Broad policy changes, rather than additional individual recommendations, are needed to address the concerns of this vulnerable population.
M2 tumor-associated macrophage mediates the maintenance of stemness to promote cisplatin resistance by secreting TGF-β1 in esophageal squamous cell carcinoma
Authors: Yang Kaige , Xie Yufang , Xue Lele , Li Fanping , Luo Chenghua , Liang Weihua , Zhang Haijun , Li Ya , Ren Yilin , Zhao Mengmeng , Wang Weinan , Liu Jia , Shen Xihua , Zhou Wenhu , Fei Jing , Chen Weigang , Gu Wenyi , Wang Lianghai , Li Feng , Hu Jianming
Published: January 2023

Background

Esophageal squamous cell carcinoma (ESCC) is a deadly gastrointestinal malignancy, and chemotherapy resistance is a key factor leading to its poor prognosis. M2 tumor-associated macrophages (M2-TAMs) may be an important cause of chemoresistance in ESCC, but its exact mechanism is still unclear.

Methods

In order to study the role of M2-TAMs in ESCC chemoresistance, CCK-8, clone formation assay, flow cytometric apoptosis assay, qRT-PCR, western blotting, and serum-free sphere formation assays were used. In vivo animal experiments and human ESCC tissues were used to confirm the findings.

Results

In vitro and in vivo animal experiments, M2-TAMs reduced the sensitivity of ESCC cells to cisplatin. Mechanistically, M2-TAMs highly secreted TGF-β1 which activated the TGFβR1-smad2/3 pathway to promote and maintain the stemness characteristic of ESCC cells, which could inhibit the sensitivity to cisplatin. Using TGFβ signaling inhibitor SB431542 or knockdown of TGFβR1 could reverse the cisplatin resistance of ESCC cells. In 92 cases of human ESCC tissues, individuals with a high density of M2-TAMs had considerably higher levels of TGF-β1. These patients also had worse prognoses and richer stemness markers.

Conclusion

TGF-β1 secreted from M2-TAMs promoted and maintained the stemness characteristic to induce cisplatin resistance in ESCC by activating the TGFβ1-Smad2/3 pathway.
Sorting through life: evaluating patient-important measures of success in a medication for opioid use disorder (MOUD) treatment program
Authors: Reed Megan K. , Smith Kelsey R. , Ciocco Francesca , Hass Richard W. , Cox Avery Lin , Kelly Erin L. , Weinstein Lara C.
Published: January 2023

Background

Medication for opioid use disorder (MOUD) is the gold standard treatment for opioid use disorder. Traditionally, “success” in MOUD treatment is measured in terms of program retention, adherence to MOUD, and abstinence from opioid and other drug use. While clinically meaningful, these metrics may overlook other aspects of the lives of people with opioid use disorder (OUD) and surprisingly do not reflect the diagnostic criteria for OUD.

Methods

Authors identified items for a pilesorting task to identify participant-driven measures of MOUD treatment success through semi-structured interviews. Interviews were transcribed verbatim and coded in Nvivo using directed and conventional content analysis to identify measures related to treatment success and quality of life goals. Participants of a low-threshold MOUD program were recruited and asked to rank identified measures in order of importance to their own lives. Multidimensional scaling (MDS) compared the similarity of items while non-metric MDS in R specified a two-dimensional solution. Descriptive statistics of participant demographics were generated in SPSS.

Results

Sixteen semi-structured interviews were conducted between June and August 2020 in Philadelphia, PA, USA, and 23 measures were identified for a pilesorting activity. These were combined with 6 traditional measures for a total list of 29 items. Data from 28 people were included in pilesorting analysis. Participants identified a combination of traditional and stakeholder-defined recovery goals as highly important, however, we identified discrepancies between the most frequent and highest ranked items within the importance categories. Measures of success for participants in MOUD programs were complex, multi-dimensional, and varied by the individual. However, some key domains such as emotional well-being, decreased drug use, and attendance to basic functioning may have universal importance. The following clusters of importance were identified: emotional well-being, decreased drug use, and human functioning.

Conclusions

Outcomes from this research have practical applications for those working to provide services in MOUD programs. Programs can use aspects of these domains to both provide patient-centered care and to evaluate success. Specifics from the pilesorting results may also inform approaches to collaborative goal setting during treatment.
Profiles of quality of outpatient care use, associated sociodemographic and clinical characteristics, and adverse outcomes among patients with substance-related disorders
Authors: Fleury Marie-Josée , Cao Zhirong , Grenier Guy , Huỳnh Christophe
Published: January 2023

Background

This study identified patient profiles in terms of their quality of outpatient care use, associated sociodemographic and clinical characteristics, and adverse outcomes based on frequent emergency department (ED) use, hospitalization, and death from medical causes.

Methods

A cohort of 18,215 patients with substance-related disorders (SRD) recruited in addiction treatment centers was investigated using Quebec (Canada) health administrative databases. A latent class analysis was produced, identifying three profiles of quality of outpatient care use, while multinomial and logistic regressions tested associations with patient characteristics and adverse outcomes, respectively.

Results

Profile 1 patients (47% of the sample), labeled “Low outpatient service users”, received low quality of care. They were mainly younger, materially and socially deprived men, some with a criminal history. They had more recent SRD, mainly polysubstance, and less mental disorders (MD) and chronic physical illnesses than other Profiles. Profile 2 patients (36%), labeled “Moderate outpatient service users”, received high continuity and intensity of care by general practitioners (GP), while the diversity and regularity in their overall quality of outpatient service was moderate. Compared with Profile 1, they  were older, less likely to be unemployed or to live in semi-urban areas, and most had common MD and chronic physical illnesses. Profile 3 patients (17%), labeled “High outpatient service users”, received more intensive psychiatric care and higher quality of outpatient care than other Profiles. Most Profile 3 patients lived alone or were single parents, and fewer lived in rural areas or had a history of homelessness, versus Profile 1 patients. They were strongly affected by MD, mostly serious MD and personality disorders. Compared with Profile 1, Profile 3 had more frequent ED use and hospitalizations, followed by Profile 2. No differences in death rates emerged among the profiles.

Conclusions

Frequent ED use and hospitalization were strongly related to patient clinical and sociodemographic profiles, and the quality of outpatient services received to the severity of their conditions. Outreach strategies more responsive to patient needs may include motivational interventions and prevention of risky behaviors for Profile 1 patients, collaborative GP-psychiatrist care for Profile 2 patients, and GP care and intensive specialized treatment for Profile 3 patients.
IMPT of head and neck cancer: unsupervised machine learning treatment planning strategy for reducing radiation dermatitis
Authors: Padannayil Noufal Manthala , Sharma Dayananda Shamurailatpam , Nangia Sapna , Patro Kartikeshwar C. , Gaikwad Utpal , Burela Nagarjuna
Published: January 2023

Radiation dermatitis is a major concern in intensity modulated proton therapy (IMPT) for head and neck cancer (HNC) despite its demonstrated superiority over contemporary photon radiotherapy. In this study, dose surface histogram data extracted from forty-four patients of HNC treated with IMPT was used to predict the normal tissue complication probability (NTCP) of skin. Grades of NTCP-skin were clustered using the K-means clustering unsupervised machine learning (ML) algorithm. A new skin-sparing IMPT (IMPT-SS) planning strategy was developed with three major changes and prospectively implemented in twenty HNC patients. Across skin surfaces exposed from 10 (S10) to 70 (S70) GyRBE, the skin's NTCP demonstrated the strongest associations with S50 and S40 GyRBE (0.95 and 0.94). The increase in the NTCP of skin per unit GyRBE is 0.568 for skin exposed to 50 GyRBE as compared to 0.418 for 40 GyRBE. Three distinct clusters were formed, with 41% of patients in G1, 32% in G2, and 27% in G3. The average (± SD) generalised equivalent uniform dose for G1, G2, and G3 clusters was 26.54 ± 6.75, 38.73 ± 1.80, and 45.67 ± 2.20 GyRBE. The corresponding NTCP (%) were 4.97 ± 5.12, 48.12 ± 12.72 and 87.28 ± 7.73 respectively. In comparison to IMPT, new IMPT-SS plans significantly (P < 0.01) reduced SX GyRBE, gEUD, and associated NTCP-skin while maintaining identical dose volume indices for target and other organs at risk. The mean NTCP-skin value for IMPT-SS was 34% lower than that of IMPT. The dose to skin in patients treated prospectively for HNC was reduced by including gEUD for an acceptable radiation dermatitis determined from the local patient population using an unsupervised MLA in the spot map optimization of a new IMPT planning technique. However, the clinical finding of acute skin toxicity must also be related to the observed reduction in skin dose.
Clinical efficacy of styloid incision truncation via percutaneous punching in treating styloid process syndrome
Authors: Zheng Yuebin , Yan Bincheng , Zhong Huacai , Yi Wang , Yang Yirong , Wang Qian
Published: January 2023

Objective

To clarify the clinical efficacy of styloid incision truncation via percutaneous punching in treating styloid process (styloid) syndrome.

Methods

The clinical data of 40 styloid syndrome patients treated in our hospital from July 2018 to August 2021 were chosen and divided into an observation group and a control group in a random manner, with 20 cases in each. The control group received treatment with styloid truncation via an external cervical approach, and the observation group received treatment with styloid incision truncation via percutaneous punching. The operation time, intraoperative blood loss, length of truncated styloid, clinical efficacy, pain scores, postoperative complications and inflammatory cytokine levels were assessed in the both groups.

Results

The intraoperative blood loss, operation time, length of truncated styloid and hospital stay in the observation group were significantly lower than those in the control group (P < 0.05). VAS pain scores were higher in both groups after the operation compared to before the operation. However, the observation group showed a statistically significant reduction in comparison with the control group (P < 0.05). The treatment effectiveness and complication rates of the two groups exhibited significant differences (P < 0.05). After the operation, TNF-α, CRP, and IL-6 levels in both groups were elevated compared to those before the operation. The observation group, however, showed significant depletion compared to the control group (P < 0.05).

Conclusion

Styloid incision truncation via percutaneous punching was not only effective in treating styloid syndrome, but also caused less trauma and fewer complications. It promotes patient recovery and requires a simple operation, making it worthy of promotion in hospitals.
Androgen increases klotho expression via the androgen receptor-mediated pathway to induce GCs apoptosis
Authors: Zeng Xin , Zhong Qiaoqing , Li Ming , Liu Yating , long Shuanglian , Xie Yuanjie , Mo Zhongcheng
Published: January 2023

Background

Many epidemiological studies have shown that anovulatory polycystic ovary syndrome (PCOS) is accompanied by hyperandrogenism. However, the exact mechanism of hyperandrogen-induced anovulation remains to be elucidated. In this study, we aimed to investigate the potential mechanism of anovulation in PCOS. To investigate the role of klotho as a key factor in the androgen receptor (AR)-mediated development of PCOS, we investigated the effects of testosterone on ovarian klotho expression in vivo and in vitro.

Results

Testosterone propionate (TP)-induced rats showed cycle irregularity, hyperandrogenism, polycystic ovarian changes, dyslipidemia. However, inhibition of AR expression could relieve PCOS traits. We also found that AR and klotho showed relatively high expression in PCOS rat ovarian tissue and in TP-induced granulosa cells (GCs), which was inhibited by the addition of flutamide. TP-induced GCs apoptosis was suppressed by AR antagonist, as well as silencing klotho expression in human GCs. Chromatin immunoprecipitation assay demonstrated that AR indirectly binds to the klotho promoter.

Conclusions

Our results demonstrated TP mediates the expression of klotho via androgen receptor and klotho alterations could be a reason for ovarian dysfunction in PCOS.
Prehospital vital sign monitoring in paediatric patients: an interregional study of educational interventions
Authors: Nielsen Vibe Maria Laden , Søvsø Morten Breinholt , Kløjgård Torben Anders , Skals Regitze Gyldenholm , Corfield Alasdair Ross , Bender Lars , Lossius Hans Morten , Mikkelsen Søren , Christensen Erika Frischknecht
Published: January 2023

Background

Prehospital vital sign documentation in paediatric patients is incomplete, especially in patients ≤ 2 years. The aim of the study was to increase vital sign registration in paediatric patients through specific educational initiatives.

Methods

Prospective quasi-experimental study with interrupted time-series design in the North Denmark and South Denmark regions. The study consecutively included all children aged < 18 years attended by the emergency medical service (EMS) from 1 July 2019 to 31 December 2021. Specific educational initiatives were conducted only in the North Denmark EMS and included video learning and classroom training based on the European Paediatric Advanced Life Support principles. The primary outcome was the proportion of patients who had their respiratory rate, peripheral capillary oxygen saturation, heart rate and level of consciousness recorded at least twice. We used a binomial regression model stratified by age groups to compare proportions of the primary outcome in the pre- and post-intervention periods in each region.

Results

In North Denmark, 7551 patients were included, while 15,585 patients from South Denmark were used as a reference. Virtually all of the North Denmark EMS providers completed the video learning (98.7%). The total study population involved patients aged ≤ 2 months (5.5%), 3–11 months (7.4%), 1–2 years (18.8%), 3–7 years (16.2%) and ≥ 8 years (52.1%). In the intervention region, the primary outcome increased from the pre- to the post-intervention period from 35.3% to 40.5% [95% CI for difference 3.0;7.4]. There were large variations in between age groups with increases from 18.8% to 27.4% [95% CI for difference 5.3;12.0] among patients aged ≤ 2 years, from 33.5% to 43.7% [95% CI for difference 4.9;15.5] among patients aged 3–7 years and an insignificant increase among patients aged ≥ 8 years (from 46.4% to 47.9% [95% CI for difference − 1.7;4.7]). In the region without the specific educational interventions, proportions were steady for all age groups throughout the entire study period.

Conclusions

Mandatory educational initiatives for EMS providers were associated with an increase in the extent of vital sign registration in paediatric patients ≤ 7 years. Incomplete vital registration was associated with, but not limited to non-urgent cases.
Acute otitis media-related facial nerve palsy in a child: a case report and a literary review
Authors: Castellazzi Massimo Luca , Torretta Sara , Pietro Giada Maria Di , Ciabatta Annaclara , Capaccio Pasquale , Caschera Luca , Marchisio Paola
Published: January 2023

Background

Acute otitis media has become a rare cause of facial palsy in children. A high index of suspicion is essential to achieve the diagnosis and to properly treat this condition to avoid permanent neurological sequelae.

Case presentation

A case of acute otitis media-related facial nerve palsy in an 18 months-old child is described and a review of the recent literature about the clinical presentation, diagnosis, and management of this condition is performed.

Conclusions

Facial paralysis is an uncommon complication of acute otitis media that requires appropriate care. As highlighted in our report, the treatment of facial nerve palsy secondary to otitis media should be conservative, using antibiotics and corticosteroids. The role of antiviral is still a matter of debate. Myringotomy and a ventilation tube should be added when spontaneous perforation of the tympanic membrane is not present. More aggressive surgical approach should be considered only when there is no significant improvement.
Vitamin C boosts DNA demethylation in TET2 germline mutation carriers
Authors: Taira Aurora , Palin Kimmo , Kuosmanen Anna , Välimäki Niko , Kuittinen Outi , Kuismin Outi , Kaasinen Eevi , Rajamäki Kristiina , Aaltonen Lauri A.
Published: January 2023

Background

Accurate regulation of DNA methylation is necessary for normal cells to differentiate, develop and function. TET2 catalyzes stepwise DNA demethylation in hematopoietic cells. Mutations in the TET2 gene predispose to hematological malignancies by causing DNA methylation overload and aberrant epigenomic landscape. Studies on mice and cell lines show that the function of TET2 is boosted by vitamin C. Thus, by strengthening the demethylation activity of TET2, vitamin C could play a role in the prevention of hematological malignancies in individuals with TET2 dysfunction. We recently identified a family with lymphoma predisposition where a heterozygous truncating germline mutation in TET2 segregated with nodular lymphocyte-predominant Hodgkin lymphoma. The mutation carriers displayed a hypermethylation pattern that was absent in the family members without the mutation.

Methods

In a clinical trial of 1 year, we investigated the effects of oral 1 g/day vitamin C supplementation on DNA methylation by analyzing genome-wide DNA methylation and gene expression patterns from the family members.

Results

We show that vitamin C reinforces the DNA demethylation cascade, reduces the proportion of hypermethylated loci and diminishes gene expression differences between TET2 mutation carriers and control individuals.

Conclusions

These results suggest that vitamin C supplementation increases DNA methylation turnover and provide a basis for further work to examine the potential benefits of vitamin C supplementation in individuals with germline and somatic TET2 mutations.

Trial registration: This trial was registered at EudraCT with reference number of 2018-000155-41 (01.04.2019).

Graphical Abstract
Mutational signature of extracranial meningioma metastases and their respective primary tumors
Authors: Biczok A. , Thorsteinsdottir J. , Karschnia P. , Ruf V. C. , Tonn J. C. , Herms J. , Schichor C. , Dorostkar M. M.
Published: January 2023

Extracranial metastases of intracranial meningiomas are rare. Little is known about the mutational pattern of these tumors and their metastatic seeding. Here, we retrospectively explored the molecular alterations of these metastatic lesions and their respective intracranial tumor manifestations.

Histology and genome sequencing were performed in intracranial meningiomas and their extracranial metastatic lesions operated upon between 2002 and 2021. Next-generation DNA/RNA sequencing (NGS) and methylome analysis were performed to determine molecular alterations.

We analyzed the tumors of five patients with clinically suspected metastases of a meningioma using methylome analysis and next generation panel sequencing of the primary tumors as well as the metastatic lesions. Metastases were found in the spinal cord and one in the lung. In four of these patients, molecular analyses confirmed metastatic disease, while the fifth patient was found to harbor two molecularly distinct meningiomas. On pathological assessment, the primary lesions ranged from CNS WHO grades 1 to 3 (integrated molecular-morphologic meningioma classification scores 2 to 6). Of the four true metastatic cases, three out of the four metastasizing tumors harbored alterations in the BAP1 gene, comprising a stop-mutation combined with copy-number loss (WHO grade 1), copy number loss (WHO grade 3) and a frameshift mutation (WHO grade 2). Furthermore, the latter was confirmed to harbor a BAP1 tumor predisposition syndrome. The fourth metastasizing tumor had copy-number losses in NF2 and PTEN. Only one of four showed CDKN2A homozygous deletion; none showed TERT promotor mutation.

Our results molecularly confirm true metastatic disease in four meningioma patients. BAP1 gene alterations were the most frequent. Larger cohorts, most likely from multicenter studies are necessary to evaluate the role of BAP-1 alterations to further understand the metastatic spread in meningiomas. for metastatic spread and might indicate patients at risk for metastatic spread. Further explorations within larger cohorts are necessary to validate these findings which might influence the clinical management in the future.