bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical manifestations and outcome of viral acute lower respiratory infection in hospitalised children in Myanmar
Authors: Kamata Kazuhiro , Thein Khin Nyo , Di Ja Lasham , Win Nay Chi , Win Su Mon Kyaw , Suzuki Yuko , Ito Ai , Osada Hidekazu , Chon Irina , Phyu Wint Wint , Aizawa Yuta , Ikuse Tatsuki , Ota Tomomi , Kyaw Yadanar , Tin Htay Htay , Shobugawa Yugo , Watanabe Hisami , Saito Reiko , Saitoh Akihiko
Published: April 2022

Background

Acute lower respiratory infection (ALRI) remains the leading cause of death in children worldwide, and viruses have been the major cause of ALRI. In Myanmar, ALRI is associated with high morbidity and mortality in children, and detailed information on ALRI is currently lacking.

Methods

This prospective study investigated the viral aetiologies, clinical manifestations, and outcomes of ALRI in hospitalised children aged 1 month to 12 years at the Yankin Children Hospital, Yangon, Myanmar from May 2017 to April 2019. The sample size was set to 300 patients for each year. Two nasopharyngeal swabs were obtained for the patients with suspected viral ALRI; one for rapid tests for influenza and respiratory syncytial virus (RSV), and the other for real-time PCR for the 16 ALRI-causing viruses. Pneumococcal colonization rates were also investigated using real-time PCR. Clinical information was extracted from the medical records, and enrolled patients were categorised by age and severity for comparison.

Results

Among the 5463 patients admitted with a diagnosis of ALRI, 570 (10.4%) were enrolled in this study. The median age of the patients was 8 months (interquartile range, 4–15 months). The most common symptoms were cough (93%) and difficulty in breathing (73%), while the most common signs of ALRI were tachypnoea (78%) and chest indrawing (67%). A total of 16 viruses were detected in 502 of 570 patients’ samples (88%), with RSV B (36%) and rhinovirus (28%) being the most commonly detected. Multiple viruses were detected in 221 of 570 samples (37%) collected from 570 patients. Severe ALRI was diagnosed in 107 of 570 patients (19%), and RSV B and human rhinovirus were commonly detected. The mortality rate was 5%; influenza virus A (29%) and RSV B (21%) were commonly detected, and stunting and lack of immunization were frequently observed in such cases. Additionally, 45% (259/570) of the patients had pneumococcal colonization.

Conclusions

Viral ALRI in hospitalised children with a median of 8 months has significant morbidity and mortality rates in Myanmar. RSV and rhinovirus were the most commonly detected from nasopharyngeal swabs, while influenza virus and RSV were the most frequently associated with fatal cases.
Accuracy of advanced deep learning with tensorflow and keras for classifying teeth developmental stages in digital panoramic imaging
Authors: Mohammad Norhasmira , Muad Anuar Mikdad , Ahmad Rohana , Yusof Mohd Yusmiaidil Putera Mohd
Published: April 2022

Background

This study aims to propose the combinations of image processing and machine learning model to segment the maturity development of the mandibular premolars using a Keras-based deep learning convolutional neural networks (DCNN) model.

Methods

A dataset consisting of 240 images (20 images per stage per sex) of retrospect digital dental panoramic imaging of patients between 5 and 14 years of age was retrieved. In image preprocessing, abounding box with a dimension of 250 × 250 pixels was assigned to the left mandibular first (P1) and second (P2) permanent premolars. The implementation of dynamic programming of active contour (DP-AC) and convolutions neural network on images that require the procedure of image filtration using Python TensorFlow and Keras libraries were performed in image segmentation and classification, respectively.

Results

Image segmentation using the DP-AC algorithm enhanced the visibility of the image features in the region of interest while suppressing the image's background noise. The proposed model has an accuracy of 97.74%, 96.63% and 78.13% on the training, validation, and testing set, respectively. In addition, moderate agreement (Kappa value = 0.58) between human observer and computer were identified. Nonetheless, a robust DCNN model was achieved as there is no sign of the model's over-or under-fitting upon the learning process.

Conclusions

The application of digital imaging and deep learning techniques used by the DP-AC and convolutions neural network algorithms to segment and identify premolars provides promising results for semi-automated forensic dental staging in the future.
KCNQ1 and lymphovascular invasion are key features in a prognostic classifier for stage II and III colon cancer
Authors: Uil Sjoerd H. , Coupé Veerle M. H. , Bril Herman , Meijer Gerrit A. , Fijneman Remond J. A. , Stockmann Hein B. A. C.
Published: April 2022

Background

The risk of recurrence after resection of a stage II or III colon cancer, and therefore qualification for adjuvant chemotherapy (ACT), is traditionally based on clinicopathological parameters. However, the parameters used in clinical practice are not able to accurately identify all patients with or without minimal residual disease. Some patients considered ‘low-risk’ do develop recurrence (undertreatment), whilst other patients receiving ACT might not have developed recurrence at all (overtreatment). We previously analysed tumour tissue expression of 28 protein biomarkers that might improve identification of patients at risk of recurrence. In the present study we aimed to build a prognostic classifier based on these 28 biomarkers and clinicopathological parameters.

Methods

Classification and regression tree (CART) analysis was used to build a prognostic classifier based on a well described cohort of 386 patients with stage II and III colon cancer. Separate classifiers were built for patients who were or were not treated with ACT. Routine clinicopathological parameters and tumour tissue immunohistochemistry data were included, available for 28 proteins previously published. Classification trees were pruned until lowest misclassification error was obtained. Survival of the identified subgroups was analysed, and robustness of the selected CART variables was assessed by random forest analysis (1000 trees).

Results

In patients not treated with ACT, prognosis was estimated best based on expression of KCNQ1. Poor disease-free survival (DFS) was observed in those with loss of expression of KCNQ1 (HR = 3.38 (95% CI 2.12 – 5.40); p < 0.001). In patients treated with ACT, key prognostic factors were lymphovascular invasion (LVI) and expression of KCNQ1. Patients with LVI showed poorest DFS, whilst patients without LVI and high expression of KCNQ1 showed most favourable survival (HR = 7.50 (95% CI 3.57—15.74); p < 0.001). Patients without LVI and loss of expression of KCNQ1 had intermediate survival (HR = 3.91 (95% CI 1.76 – 8.72); p = 0.001).

Conclusion

KCNQ1 and LVI were identified as key features in prognostic classifiers for disease-free survival in stage II and III colon cancer patients.
Assessing and improving public mental health literacy concerning rTMS
Authors: Morrison Amanda S. , Uusberg Andero , Ryan Julia , Goldenberg Amit , Etkin Amit , Gross James J.
Published: April 2022

Background

Repetitive transcranial magnetic stimulation (rTMS) has received empirical support as a viable treatment alternative for treatment-resistant major depressive disorder. Nevertheless, patients and the public-at-large may be hesitant to adopt rTMS. In three studies, we sought to (1) assess and (2) improve public perceptions of rTMS as a treatment for depression.

Methods

In Study 1 (N = 107), we administered questionnaires on Amazon’s Mechanical Turk (MTurk) to individuals from the US and Canada in a cross-sectional design to assess perceptions of rTMS compared to psychopharmacology, electroconvulsive therapy (ECT), and talk therapy. In Study 2 (N = 106), we again used an MTurk sample and a cross-sectional design to assess perceptions of rTMS after providing participants with a relatively long description of rTMS. In Study 3 (N = 308), we conducted an experiment in undergraduate students. Participants were randomized to one of four experimental conditions manipulating participants’ understanding of the causal mechanisms of depression prior to assessing their perceptions of rTMS.

Results

Public perceptions of rTMS were more negative than pharmacotherapy and talk therapy but not ECT (Study 1). rTMS perceptions were notably better when participants were given thorough information about rTMS procedures, pain, and side-effects (Study 2), compared to the previous study when they were given a very brief description of rTMS. Finally, perceptions of rTMS were significantly better when participants were given a brain circuitry-based causal explanation of depression compared to when they were given a psychological explanation of the causes of depression (Study 3).

Conclusions

Public perceptions of rTMS are relatively poor. To improve rTMS acceptability, practitioners should carefully consider patients’ prior attitudes and beliefs when explaining rTMS as a treatment alternative. Given that beliefs can have powerful effects on treatment outcome (e.g., placebo, nocebo), future research should explore whether rTMS effects on depression can be improved by facilitating less negative perceptions of rTMS.
Effectiveness of a community health worker-led case management programme to improve outcomes for people with psychotic disorders in Thailand: a one-year prospective cohort study
Authors: Jirapramukpitak Tawanchai , Jaisin Kankamol , Supanya Suttha , Takizawa Patcharapim
Published: April 2022

Background

Intensive case management (ICM) programmes for psychotic patients are effective in improving outcomes, but often unfeasible in resource-poor settings, as they typically require extensive human resources and expertise. We developed and evaluated the effectiveness of a less intensive case management program (LICM), led by community health workers, on one-year social functioning and service use.

Methods

A prospective cohort study was conducted on patients aged 18 and above residing in a hospital catchment area. Outcomes were compared between LICM (n = 64) and non-LICM participants (n = 485). A counterfactual framework approach was applied to assess causal effects of the LICM on outcomes. The programme effectiveness was analyzed by augmented-inverse probability of treatment weighting (AIPW) to estimate potential outcome mean (POM) and average treatment effect (ATE). Outcomes were employment status and use of emergency, inpatient and outpatient services. Analyses were stratified by the number of previous psychotic relapse (≤ 1, > 1) to assess heterogeneity of treatment effect on those in an early and later stages of psychotic illness.

Results

In the early-stage cohort, the likelihood of being employed at one year post-baseline was significantly greater in LICM participants than non-LICM participants (ATE 0.10, 95%CI 0.05–0.14, p < 0.001), whereas service use of all types, except outpatient, was not significantly different between the two groups. In the later-stage cohort, the likelihoods of employment between the two groups at post-baseline were similar (ATE -0.02, 95%CI -0.19–0.15, p = 0.826), whereas service use of all types was significantly higher in LICM participants.

Conclusion

LICM in a setting where community mental services are scarce may benefit those at an early stage of psychotic illness, by leading to better social functioning and no higher use of unscheduled services at the end of the programme, possibly through their better prognosis and medication adherence. A more intensive case management model may be appropriate for those in a later stage of the illness.
Trajectories of depressive symptoms among community-dwelling Korean older adults: findings from the Korean longitudinal study of aging (2006–2016)
Authors: Shin Jinhee , Cho Eunhee
Published: April 2022

Background

Depression among older adults is an important public health concern associated with increased risk of suicide and decreased physical, cognitive, and social functioning. This study identified trajectories of depressive symptoms and investigated predictive variables of group-based trajectory modeling among Korean community-dwelling older adults.

Methods

Participants comprised 2016 community-dwelling Korean adults over 65 years. Data from the years 2006–2016 of the Korean Longitudinal Study of Aging, a nationally representative panel survey that has been conducted every two years since 2006, were used. We employed a group-based trajectory modeling analysis to identify depressive symptom trajectories. Multinomial logistic regression analysis was conducted to identify predictors of each class of depressive symptoms.

Results

Five depressive symptom trajectory groups were identified: Group 1, “None” (28.9%); Group 2, “Slowly worsening” (24.3%); Group 3, “Rapidly worsening” (17.5%); Group 4 “Improving” (12.4%); and Group 5, “Persistently severe” (16.9%). Older adults followed five distinct depressive symptom trajectories over 10 years. Mini-Mental State Examination scores, number of chronic diseases, educational level, and social activity were predictors associated with increasing depressive symptoms.

Conclusions

This study showed that many older adults living in the community have depressive symptoms. To prevent and treat depression and aid successful mental health aging among older adults, the development of interventions should be tailored to target specific needs for each symptom trajectory. It is necessary to develop community-based interventions and strategies to identify and prevent depressive symptom trajectories among older adults.
Alcohol consumption and closed borders - how COVID-19 restrictions have impacted alcohol sales and consumption in Europe
Authors: Leifman Håkan , Dramstad Kalle , Juslin Emil
Published: April 2022

Background

The closing of bars, restaurants and international borders during the COVID-19 pandemic led to significant changes in alcohol availability. This study provides a first systematic overview of the monthly development of alcohol sales in Europe during the pandemic in order to determine the effect of closed borders on the sales and consumption of alcohol.

Methods

The study covers 72 months from January 2015 to December 2020 in 14 countries from northern, central and western Europe with excise revenue data for beer, spirits, wine separately and summed, converted into litres of pure alcohol per capita 15+ as a proxy for alcohol sales. March–December 2020 is seen as the pandemic period. The analyses consist of (1) descriptive trends of sales before and during the pandemic, (2) assessment of the pandemic impact on sales by time-series analyses and (3) case studies of countries and a region with substantial cross-border inflow or outflow of alcohol.

Results

The result shows an overall reduction in alcohol sales with 3.6% during the pandemic. Nevertheless, the results differ based on the level of cross-border purchasing flows pre-pandemic, as countries with high cross-border inflow saw an increase in domestic sales as the pandemic hit. Norway, for example, saw a 23% increase in domestic sales during the pandemic period March–December 2020 compared to the same period in 2019.

Conclusion

The closing of intra-European borders had a significant redistributing effect on alcohol sales. While noting sales increases, cross-border inflow countries generally saw a decrease in total amount of alcohol consumed per capita as not all cross-border purchases were replaced by domestic sales. This has important policy implications as large volumes of cross-border inflow of alcohol can negatively affect excise revenue as well as public health outcomes.

The methodology can be used to further explore the reliance of different purchasing streams in a domestic alcohol market.
Sustaining Maternal and Neonatal Tetanus Elimination (MNTE) in countries that have been validated for elimination – progress and challenges
Authors: Yusuf Nasir , Steinglass Robert , Gasse Francois , Raza Azhar , Ahmed Bilal , Blanc Diana Chang , Yakubu Ahmadu , Gregory Christopher , Tohme Rania A.
Published: April 2022

Background

As of October 2021, 47 (80%) of the 59 countries, identified at highest risk for Maternal and Neonatal Tetanus (MNT), had been validated for elimination. We assessed sustainability of MNT elimination (MNTE) in 28 countries that were validated during 2011‒2020.

Methods

We assessed the attainment of the following MNTE sustainability indicators: 1) ≥ 90% coverage with three doses of Diphtheria-Tetanus-Pertussis vaccine (DTP3) among infants < 1 year, 2) ≥ 80% coverage with at least two doses of tetanus toxoid-containing vaccine (TTCV2 +) among pregnant women, 3) ≥ 80% protection at birth (PAB), 4) ≥ 70% skilled birth attendance (SBA), and 4) ≥ 80% first (ANC1) and fourth antenatal care (ANC4) visits. We assessed the introduction of TTCV booster doses. Data sources included the 2020 WHO /UNICEF Joint Reporting Forms, and the latest Demographic and Health Survey (DHS) or Multi-Indicator Cluster Surveys (MICS) for each country, if available. We reviewed literature and used DHS/MICS data to identify barriers to sustaining MNTE.

Results

Of 28 assessed countries, 7 (25%) reported ≥ 90% DTP3 coverage, 4 of 26 (16%) reported ≥ 80% TTCV2 + coverage, and 23 of 27 (85%) reported ≥ 80% PAB coverage. Based on DHS/MICS in 15 of the 28 countries, 10 (67%) achieved ≥ 70% SBA delivery, 13 (87%) achieved ≥ 80% ANC1 visit coverage, and 3 (20%) ≥ 80% ANC4 visit coverage. We observed sub-optimal coverage in many countries at the subnational level. The first, second and third booster doses of TTCV respectively have been introduced in 6 (21%), 5 (18%), and 1 (4%) of 28 countries. Only three countries conducted post-MNTE validation assessments. Barriers to MNTE sustainability included: competing program priorities, limited resources to introduce TTCV booster doses and implement corrective immunization in high-risk districts and socio-economic factors.

Conclusions

Despite good performance of MNTE indicators in several countries, MNTE sustainability appears threatened in some countries. Integration and coordination of MNTE activities with other immunization activities in the context of the Immunization Agenda 2030 lifecourse vaccination strategy such as providing tetanus booster doses in school-based vaccination platforms, during measles second dose and HPV vaccination, and integrating MNTE post-validation assessments with immunization program reviews will ensure MNTE is sustained.
Association between sleep duration and cardiometabolic factors in adolescents
Authors: Confortin Susana Cararo , Aristizábal Liliana Yanet Gómez , da Silva Magalhães Elma Izze , Barbosa Aline Rodrigues , Ribeiro Cecilia Claudia Costa , Batista Rosângela Fernandes Lucena , Silva Antônio Augusto Moura da
Published: April 2022

Background

The sleep reduction can change healthy people's hemodynamic control and cardiovascular regulation through increased inflammatory response and altered endothelial function. The objective the study to analyze the association between sleep duration and cardiometabolic risk factors in adolescents in the birth cohort of São Luís (1997/98).

Methods

This is a cross-sectional study with adolescents participating in the birth cohort of São Luís (1997/98). Sleep duration was evaluated using accelerometer data (Actigraph wGT3X-BT). Glycemia, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c) and triglycerides were considered cardiometabolic factors. The Directed Acyclic Graph (DAG) was used to identify the minimum set of adjustment for confounding.

Results

Out of 1,268 adolescents, 50.3% of them were male. The prevalence of sleep duration of less than 6 h per day was 31.1%. The mean glycemia value was 91.8 mg/dL (± 15.9), DBP was 71.3 mmHg (± 7.5), SBP was 114.9 mmHg (± 12.3), HDL was 48.5 mg/dL (± 11.6), LDL was 89.0 mg/dL (± 25.7), the total cholesterol was 156.0 mg/dL (± 31.1), and triglycerides was 93.6 mg/dL (± 47.2). The crude analysis showed an association between sleep duration and SBP and LDL-c. In the adjusted analysis, the associations did not remain.

Conclusion

Our study showed no association between sleep duration and cardiometabolic outcomes in adolescents.
Correlation between musculoskeletal mass and perfusion in patients with gastrointestinal malignancy: a preliminary study based on quantitative CT and CT perfusion
Authors: Ji Rui , Zhang Lin , Shen Yongju , Tang Rui , Tu Yun , Tang Guangyu , Zhu Jingqi
Published: April 2022

Background

To investigate the correlation between musculoskeletal mass and perfusion using quantitative computer tomography (QCT) and CT perfusion (CTP) in patients with gastrointestinal malignancy.

Methods

In this prospective study, 96 patients (mean age 66 years, range 25–90; 63.5% male) with gastrointestinal malignancy underwent QCT and CTP between May 2019 and February 2021. Bone mineral density (BMD) and body composition [perivertebral muscular mass index (PMI), skeletal muscular mass index (SMI) and muscular fat fraction] were evaluated through QCT. Musculoskeletal perfusion parameters were measured by CTP. Differences in these parameters between (or among) two (or three) groups (grouped by BMD, SMI, and TNM staging) were analyzed.

Results

There were significant differences in PMI and muscular fat fraction among normal (n = 30), osteopenia (n = 43), and osteoporosis (n = 23) groups (both P < 0.001). Blood flow (r = 0.336, P = 0.001; adjusted for age and gender, r = 0.383, P < 0.001), blood volume (r = 0.238, P = 0.011; adjusted for age and gender, r = 0.329, P = 0.001), and flow extraction product (r = 0.217, P = 0.034; adjusted for age and gender, r = 0.320, P = 0.002) vaules of vertebral perfusion showed positive correlation with BMD. However, the relationships between PMI and perfusion parameters of perivertebral muscle were not significant. No significant differences were found in musculoskeletal mass and perfusion parameters between different TNM staging.

Conclusions

The changes of bone mass and perivertebral muscular mass in patients with gastrointestinal malignancy are synchronous. Decreased vertebral bone mass is accompanied with reduced perivertebral muscular mass, increased muscular fat, and decreased bone perfusion. However, the changes of perfusion in vertebra and perivertebral muscles are asynchronous. Musculoskeletal mass and perfusion have no correlation with TNM staging of the patients with gastrointestinal malignancy.

Trial registration

SHSY-IEC-4.1/20–242/01 (Registered 09–12-2020, Retrospectively registered).
Biomechanical features of drop vertical jump are different among various sporting activities
Authors: Harato Kengo , Morishige Yutaro , Kobayashi Shu , Niki Yasuo , Nagura Takeo
Published: April 2022

Background

Risk for non-contact anterior cruciate ligament (ACL) injury can be assessed based on drop vertical jump (DVJ). However, biomechanics of DVJ may differ with various sporting activities. The purpose of the present study was to clarify whether biomechanical features of DVJ are different among various sporting activities in female athletes.

Methods

A total of 42 female athletes, including 25 basketball, 8 soccer and 9 volleyball players, participated in the current investigation. DVJ was done for each female athlete using a three-dimensional motion analysis system which consisted of six cameras, two force plates and 46 retro-reflective markers. Kinematic and kinetic data were recorded for both limbs in each athlete. Simultaneously, frontal and sagittal plane views of the DVJ were recorded using two different high-resolution video cameras to evaluate Landing Error Scoring System (LESS) score. Three-dimensional biomechanical parameters at the knee joint and LESS were compared among three different sporting activities using ANOVA or Kruskal–Wallis test after confirming normality assumption. Thereafter post hoc Tukey or Steel–Dwass was utilized for multiple comparison.

Results

Soccer players had better LESS score, and peak knee flexion angle was significantly larger in soccer players compared to the other sports. In addition, knee abduction angle at initial contact (IC), peak knee abduction angle, knee internal rotation angle, and knee abduction moment within 40 ms from IC were significantly smaller in soccer players, compared to basketball players. In terms of volleyball players, knee abduction angle at IC and knee internal rotation angle at IC were significantly larger than soccer players, whereas no significant biomechanical differences were found between basketball and volleyball players.

Conclusions

From the present study, female basketball and volleyball players have worse LESS score, smaller peak knee flexion angle, greater knee abduction angle at IC and greater knee internal rotation angle at IC, compared to female soccer players. Thus, female basketball and volleyball players may have an increased risk of non-contact ACL injury during the jump-landing task, compared to soccer players. Biomechanics of DVJ depends on characteristics of the athlete's primary sport.
A retrospective and prospective study to establish a preoperative difficulty predicting model for video-assisted thoracoscopic lobectomy and mediastinal lymph node dissection
Authors: Wang Zixiao , Wang Yuhang , Sun Daqiang
Published: April 2022

Background

In previous studies, the difficulty of surgery has rarely been used as a research object. Our study aimed to develop a predictive model to enable preoperative prediction of the technical difficulty of video-assisted thoracoscopic lobectomy and mediastinal lymph node dissection using retrospective data and to validate our findings prospectively.

Methods

Collected data according to the designed data table and took the operation time as the outcome variable. A nomogram to predict the difficulty of surgery was established through Lasso logistic regression. The prospective datasets were analyzed and the outcome was the operation time.

Results

This retrospective study enrolled 351 patients and 85 patients were included in the prospective datasets. The variables in the retrospective research were selected by Lasso logistic regression (only used for modeling and not screening), and four significantly related influencing factors were obtained: FEV1/FVC (forced expiratory volume in the first second/forced vital capacity) (p < 0.001, OR, odds ratio = 0.89, 95% CI, confidence interval = 0.84–0.94), FEV1/pred FEV1 (forced expiratory volume in the first second/forced expiratory volume in the first second in predicted) (p = 0.076, OR = 0.98, 95% CI = 0.95–1.00), history of lung disease (p = 0.027, OR = 4.00, 95% CI = 1.27–15.64), and mediastinal lymph node enlargement or calcification (p < 0.001, OR = 9.78, 95% CI = 5.10–19.69). We used ROC (receiver operating characteristic) curves to evaluate the model. The training set AUC (area under curve) value was 0.877, the test set’s AUC was 0.789, and the model had a good calibration curve. In a prospective study, the data obtained in the research cohort were brought into the model again for verification, and the AUC value was 0.772.

Conclusion

Our retrospective study identified four preoperative variables that are correlated with a longer surgical time and can be presumed to reflect more difficult surgical procedures. Our prospective study verified that the variables in the prediction model (including prior lung disease, FEV1/pred FEV1, FEV1/FVC, mediastinal lymph node enlargement or calcification) were related to the difficulty.
Risk factors for periappendiceal adhesions in acute appendicitis: a retrospective comparative study
Authors: Gao Shenshuo , Guo Xiaobo , Li Leping , Jing Changqing , Ma Yan
Published: April 2022

Purpose

Acute appendicitis usually requires immediate surgical treatment, but appendectomies were difficult for some patients with severe periappendiceal adhesions. We investigated risk factors of intraoperative adhesions to help surgeons make better treatment plans for appendicitis.

Methods

We retrospectively analyzed 186 cases diagnosed with acute appendicitis and underwent surgery in Shandong Provincial Hospital affiliated to Shandong First Medical University between January 2018 and December 2019. According to the degree of intraoperative adhesions, they were divided into mild, moderate and severe groups. Then, we analyzed a number of preoperative factors contributed to adhesions, suppuration and perforation during appendectomy in 186 patients.

Results

Contrast to the moderate group (MoG) and the mild group (MiG), the severe degree of adhesions group (SG) had a higher intraoperative perforation and suppuration rate, a greater likelihood of conversion to open and more postoperative complications. Multivariable logistic regression analysis showed that recurrent appendicitis and high neutrophil percentage were independently associated with periappendiceal adhesions. The preoperative ultrasonography (US) revealed periappendiceal fluid and high neutrophil percentage were independently associated with appendix suppuration. A high preoperative neutrophil percentage was independently associated with appendix perforation.

Conclusions

Recurrent appendicitis and preoperative high neutrophil percentage were risk factors of periappendiceal adhesions; preoperative US revealed periappendiceal fluid and high neutrophil percentage were risk factors of appendix suppuration; and a high preoperative neutrophil percentage was a risk factor of appendix perforation.
Impact of temperature changes to the adhesion strength of molar tubes: an in vitro study
Authors: Palesik Benedikta , Šileikytė Kotryna , Griškevičius Julius , Stonkus Rimantas , Šidlauskas Antanas , Lopatienė Kristina
Published: April 2022

Background

The main purpose of this was to determine study adhesion strength of molar tubes bonding with a composite adhesive after exposure to a sudden change in temperature (thermal cycles).

Methods

The study sample consisted of 40 recently extracted human first permanent molars, which were randomly divided into two groups of 20: group 1 was the experimental group (affected by thermal cycles), and group 2 was the control group. Molar tubes were bonded with a light-cure tube adhesive. The experimental group teeth were dipped 2,000 times in saline at 5 °C and at 55 °C. The control group were immersed in 37 °C saline. Molar tubes for both groups were removed with an adapted Mecmesim Multitesters 2.5—I, and the data were recorded with EMPEROR software. ANOVA was used to calculate and compare the results.

Results

In the experimental group of the teeth, the maximum force was obtained at 94.2 N and the lowest force was 19.69 N. In the control group of the teeth, the maximum force was obtained at 159.1 N and the lowest force was 28.1 N. In the experimental group, the mean debonding force (59.12 N) was statically significantly smaller than in the control group (79.88 N), p = 0.0345. The forces in the control group were by 1.35 times greater than those in the experimental group.

Conclusions

The forces of the adhesion of molar tubes to the tooth surface were reduced after exposure to a sudden change in temperature (thermal cycles). The results were significantly different between the experimental group and the control group.
Suspension of face-to-face teaching and ad hoc transition to digital learning under Covid-19 conditions – a qualitative study among dental students and lecturers
Authors: Hertrampf Katrin , Wenz Hans-Jürgen , Kaduszkiewicz Hanna , Goetz Katja
Published: April 2022

Background

In mid-March 2020, the coronavirus pandemic led to a national lockdown in Germany. Face-to-face teaching was cancelled in universities for the 2020 summer semester. Teaching moved online with no prior IT testing and lecturer training. The study analyses experiences of the suspension of face-to-face teaching and the move to digitalised learning for students and lecturers of dentistry at Kiel.

Methods

In summer 2020, qualitative guided interviews were conducted with students (4th, 6th, 8th, and 10th semesters), and lecturers. Deductive and inductive qualitative content analysis of the results was carried out.

Results

Thirty-nine students (69% female) and 19 lecturers (32% female) were interviewed. Reactions to the changes in teaching were observed. Feelings ranged from an essentially positive attitude, through insecurity and uncertainty to a failure to fully appreciate the situation. The loss of social contact was lamented. Digitalisation was associated with technological challenges and additional work. However, it also fostered learning independent of time and place, and encouraged autonomy. Negative aspects of digitalisation included a lack of feedback and loss of interaction.

Conclusion

The introduction of ad hoc digitalisation challenged both students and lecturers alike. Dealing with lockdown and the changes in teaching and studying required significant flexibility.
CRISPR-mediated Bmpr2 point mutation exacerbates late pulmonary vasculopathy and reduces survival in rats with experimental pulmonary hypertension
Authors: Kabwe Jane Chanda , Sawada Hirofumi , Mitani Yoshihide , Oshita Hironori , Tsuboya Naoki , Zhang Erquan , Maruyama Junko , Miyasaka Yoshiki , Ko Hideyoshi , Oya Kazunobu , Ito Hiromasa , Yodoya Noriko , Otsuki Shoichiro , Ohashi Hiroyuki , Okamoto Ryuji , Dohi Kaoru , Nishimura Yuhei , Mashimo Tomoji , Hirayama Masahiro , Maruyama Kazuo
Published: April 2022

Background

Patients with pulmonary arterial hypertension (PAH) carrying bone morphogenetic protein receptor type 2 (Bmpr2) mutations present earlier with severe hemodynamic compromise and have poorer survival outcomes than those without mutation. The mechanism underlying the worsening clinical phenotype of PAH with Bmpr2 mutations has been largely unaddressed in rat models of pulmonary hypertension (PH) because of the difficulty in reproducing progressive PH in mice and genetic modification in rats. We tested whether a clinically-relevant Bmpr2 mutation affects the progressive features of monocrotaline (MCT) induced-PH in rats.

Methods

A monoallelic single nucleotide insertion in exon 1 of Bmpr2 (+/44insG) was generated in rats using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9, then PH, pulmonary vascular disease (PVD) and survival after MCT injection with or without a phosphodiesterase type 5 inhibitor, tadalafil, administration were assessed.

Results

The +/44insG rats had reduced BMPR2 signalling in the lungs compared with wild-type. PH and PVD assessed at 3-weeks after MCT injection were similar in wild-type and +/44insG rats. However, survival at 4-weeks after MCT injection was significantly reduced in +/44insG rats. Among the rats surviving at 4-weeks after MCT administration, +/44insG rats had increased weight ratio of right ventricle to left ventricle plus septum (RV/[LV + S]) and % medial wall thickness (MWT) in pulmonary arteries (PAs). Immunohistochemical analysis showed increased vessels with Ki67-positive cells in the lungs, decreased mature and increased immature smooth muscle cell phenotype markers in the PAs in +/44insG rats compared with wild-type at 3-weeks after MCT injection. Contraction of PA in response to prostaglandin-F2α and endothelin-1 were significantly reduced in the +/44insG rats. The +/44insG rats that had received tadalafil had a worse survival with a significant increase in RV/(LV + S), %MWT in distal PAs and RV myocardial fibrosis compared with wild-type.

Conclusions

The present study demonstrates that the Bmpr2 mutation promotes dedifferentiation of PA smooth muscle cells, late PVD and RV myocardial fibrosis and adversely impacts both the natural and post-treatment courses of MCT-PH in rats with significant effects only in the late stages and warrants preclinical studies using this new genetic model to optimize treatment outcomes of heritable PAH.
Survival and prognostic factors in patients undergoing pulmonary metastasectomy for lung metastases from retroperitoneal sarcoma
Authors: Takatsu Fumiaki , Yamamoto Hiromasa , Tomioka Yasuaki , Tanaka Shin , Shien Kazuhiko , Suzawa Ken , Miyoshi Kentaroh , Otani Shinji , Okazaki Mikio , Sugimoto Seiichiro , Yamane Masaomi , Takahashi Katsuhito , Toyooka Shinichi
Published: April 2022

Background

Soft-tissue sarcomas are rare malignancies that consist of many different histologic subtypes and arise in various locations in the body. In patients with lung metastases from retroperitoneal sarcomas, the long-term outcomes and prognostic factors are unknown. This study is a retrospective review of patients undergoing pulmonary metastasectomy for retroperitoneal sarcoma metastases at one institution, with the purpose of determining prognostic factors and clinical outcomes.

Methods

This is a single-center, retrospective cohort study of patients undergoing pulmonary metastasectomy for lung metastases from various sarcomas at Okayama University Hospital from January 2006 to December 2018. The Kaplan-Meier method and log-rank test were used for the analyses, and cut-off values of continuous variables were determined by a receiver operating characteristic curve analysis.

Results

Twenty-four patients underwent the first pulmonary metastasectomy for lung metastases from retroperitoneal sarcoma in our hospital. Leiomyosarcoma was the most common histologic subtype of retroperitoneal sarcoma (79.2%, n = 19). Median overall survival was 49.9 months, and the 3-year and 5-year survival rates after the first pulmonary metastasectomy were 62.5% and 26.4% respectively. In univariate analysis, age ≥56 years, disease-free interval < 15 months, and size of metastasis (≥ 27 mm) were associated with poor survival.

Conclusion

Pulmonary metastasectomy can be considered as an effective management strategy in retroperitoneal sarcoma patients with lung metastases in appropriately selected cases, just as it is for other sarcomas.
TET1 mutations as a predictive biomarker for immune checkpoint inhibitors in colon adenocarcinoma
Authors: Qiu Tianzhu , Wang Xiaoxuan , Du Furong , Hu Xiangjing , Sun Fujun , Song Chao , Zhao Jie
Published: April 2022

Background

The ten-eleven translocation 1 (TET1), which is essential for active DNA demethylation, plays a multifaceted role in the pathogenesis of colorectal cancer. The study has demonstrated the association of TET1 mutations with a high response to immune checkpoint inhibitors (ICIs) in diverse cancers. However, the relationship between TET1 mutations and the response to ICIs in colon cancer is still lacking.

Methods

The prognosis, predictive markers, immune characteristics, mutation number of DNA damage repair (DDR) pathways, pathway enrichment, and drug sensitivity conditions were all compared between TET1-mutated and wild-type patients with colon adenocarcinoma (COAD).

Results

The overall survival of patients with TET1 mutations in the ICI-treated cohort was significantly longer than those without (p = 0.0059). Compared with the wild-type patients, TET1-mutated patients had higher tumor mutational burden and neoantigen load, enhanced abundance of tumor-infiltrating immune cells, increased expression of immune-related genes, and mutation number of DDR pathways. Additionally, the patients with TET1 mutations were found to be more sensitive to lapatinib and 5-fluorouracil.

Conclusion

These findings suggest that TET1 mutations may serve as a potential biomarker for the response to ICIs in COAD patients.
A proteolysis-targeting chimera molecule selectively degrades ENL and inhibits malignant gene expression and tumor growth
Authors: Li Xin , Yao Yuan , Wu Fangrui , Song Yongcheng
Published: April 2022

Background

Chromosome translocations involving mixed lineage leukemia 1 (MLL1) cause acute leukemia in most infants and 5–10% children/adults with dismal clinical outcomes. Most frequent MLL1-fusion partners AF4/AFF4, AF9/ENL and ELL, together with CDK9/cyclin-T1, constitute super elongation complexes (SEC), which promote aberrant gene transcription, oncogenesis and maintenance of MLL1-rearranged (MLL1-r) leukemia. Notably, ENL, but not its paralog AF9, is essential for MLL1-r leukemia (and several other cancers) and therefore a drug target. Moreover, recurrent ENL mutations are found in Wilms tumor, the most common pediatric kidney cancer, and play critical roles in oncogenesis.

Methods

Proteolysis-Targeting Chimera (PROTAC) molecules were designed and synthesized to degrade ENL. Biological activities of these compounds were characterized in cell and mouse models of MLL1-r leukemia and other cancers.

Results

Compound 1 efficiently degraded ENL with DC50 of 37 nM and almost depleted it at ~ 500 nM in blood and solid tumor cells. AF9 (as well as other proteins in SEC) was not significantly decreased. Compound 1-mediated ENL reduction significantly suppressed malignant gene signatures, selectively inhibited cell proliferation of MLL1-r leukemia and Myc-driven cancer cells with EC50s as low as 320 nM, and induced cell differentiation and apoptosis. It exhibited significant antitumor activity in a mouse model of MLL1-r leukemia. Compound 1 can also degrade a mutant ENL in Wilms tumor and suppress its mediated gene transcription.

Conclusion

Compound 1 is a novel chemical probe for cellular and in vivo studies of ENL (including its oncogenic mutants) and a lead compound for further anticancer drug development.
EXpert consensus On Diaphragm UltraSonography in the critically ill (EXODUS): a Delphi consensus statement on the measurement of diaphragm ultrasound-derived parameters in a critical care setting
Authors: Haaksma Mark E. , Smit Jasper M. , Boussuges Alain , Demoule Alexandre , Dres Martin , Ferrari Giovanni , Formenti Paolo , Goligher Ewan C. , Heunks Leo , Lim Endry H. T. , Mokkink Lidwine B. , Soilemezi Eleni , Shi Zhonghua , Umbrello Michele , Vetrugno Luigi , Vivier Emmanuel , Xu Lei , Zambon Massimo , Tuinman Pieter R.
Published: April 2022

Background

Diaphragm ultrasonography is rapidly evolving in both critical care and research. Nevertheless, methodologically robust guidelines on its methodology and acquiring expertise do not, or only partially, exist. Therefore, we set out to provide consensus-based statements towards a universal measurement protocol for diaphragm ultrasonography and establish key areas for research.

Methods

To formulate a robust expert consensus statement, between November 2020 and May 2021, a two-round, anonymous and online survey-based Delphi study among experts in the field was performed. Based on the literature review, the following domains were chosen: “Anatomy and physiology”, “Transducer Settings”, “Ventilator Impact”, “Learning and expertise”, “Daily practice” and “Future directions”. Agreement of ≥ 68% (≥ 10 panelists) was needed to reach consensus on a question.

Results

Of 18 panelists invited, 14 agreed to participate in the survey. After two rounds, the survey included 117 questions of which 42 questions were designed to collect arguments and opinions and 75 questions aimed at reaching consensus. Of these, 46 (61%) consensus was reached. In both rounds, the response rate was 100%. Among others, there was agreement on measuring thickness between the pleura and peritoneum, using > 10% decrease in thickness as cut-off for atrophy and using 40 examinations as minimum training to use diaphragm ultrasonography in clinical practice. In addition, key areas for research were established.

Conclusion

This expert consensus statement presents the first set of consensus-based statements on diaphragm ultrasonography methodology. They serve to ensure high-quality and homogenous measurements in daily clinical practice and in research. In addition, important gaps in current knowledge and thereby key areas for research are established.

Trial registration The study was pre-registered on the Open Science Framework with registration digital object identifier https://doi.org/10.17605/OSF.IO/HM8UG.
SETDB1 interactions with PELP1 contributes to breast cancer endocrine therapy resistance
Authors: Liu Zexuan , Liu Junhao , Ebrahimi Behnam , Pratap Uday P. , He Yi , Altwegg Kristin A. , Tang Weiwei , Li Xiaonan , Lai Zhao , Chen Yidong , Shen Liangfang , Sareddy Gangadhara R. , Viswanadhapalli Suryavathi , Tekmal Rajeshwar R. , Rao Manjeet K. , Vadlamudi Ratna K.
Published: April 2022

Background

Methyltransferase SETDB1 is highly expressed in breast cancer (BC), however, the mechanisms by which SETDB1 promotes BC progression to endocrine therapy resistance remains elusive. In this study, we examined the mechanisms by which SETDB1 contribute to BC endocrine therapy resistance.

Methods

We utilized therapy sensitive (MCF7 and ZR75), therapy resistant (MCF7-TamR, MCF7-FR, MCF7-PELP1cyto, MCF7-SETDB1) estrogen receptor alpha positive (ER+)BC models and conducted in vitro cell viability, colony formation, 3-dimensional cell growth assays to investigate the role of SETDB1 in endocrine resistance. RNA-seq of parental and SETDB1 knock down ER+ BC cells was used to identify unique pathways. SETDB1 interaction with PELP1 was identified by yeast-two hybrid screen and confirmed by immunoprecipitation and GST-pull down assays. Mechanistic studies were conducted using Western blotting, reporter gene assays, RT-qPCR, and in vitro methylation assays. Xenograft assays were used to establish the role of PELP1 in SETDB1 mediated BC progression.

Results

RNA-seq analyses showed that SETDB1 regulates expression of a subset of estrogen receptor (ER) and Akt target genes that contribute to endocrine therapy resistance. Importantly, using yeast-two hybrid screen, we identified ER coregulator PELP1 as a novel interacting protein of SETDB1. Biochemical analyses confirmed SETDB1 and PELP1 interactions in multiple BC cells. Mechanistic studies confirmed that PELP1 is necessary for SETDB1 mediated Akt methylation and phosphorylation. Further, SETDB1 overexpression promotes tamoxifen resistance in BC cells, and PELP1 knockdown abolished these effects. Using xenograft model, we provided genetic evidence that PELP1 is essential for SETDB1 mediated BC progression in vivo. Analyses of TCGA datasets revealed SETDB1 expression is positively correlated with PELP1 expression in ER+ BC patients.

Conclusions

This study suggests that the PELP1/SETDB1 axis play an important role in aberrant Akt activation and serves as a novel target for treating endocrine therapy resistance in breast cancer.
Role of the radiologist in the diagnosis and management of the two forms of hepatic echinococcosis
Authors: Calame Paul , Weck Mathieu , Busse-Cote Andreas , Brumpt Eleonore , Richou Carine , Turco Celia , Doussot Alexandre , Bresson-Hadni Solange , Delabrousse Eric
Published: April 2022

Echinococcosis is a parasitic disease caused by two zoonotic tapeworms (cestodes) of the Echinocococcus genus. It can be classified as either alveolar or cystic echinococcosis. Although the two forms differ significantly in terms of imaging findings, they share similarities in terms of management and treatment. In parallel to medical treatment with albendazole (ABZ), and surgery, historically used in these diseases, various imaging-guided interventional procedures have recently emerged (drainage, stenting, or Puncture, aspiration, injection, and reaspiration (PAIR)). These options open up a new range of therapeutic options. As in oncology, multidisciplinary consultation meetings now play a major role in adapted management and patient care in hepatic echinococcosis. Consequently, diagnostic imaging and interventional expertise have brought radiologists to the fore as important members of these multidisciplinary team. The radiologist will need to evaluate parasite activity in both forms of the disease, to guide the choice of the appropriate therapy from among medical treatment, interventional radiology procedures and/or surgical treatment. Knowledge of the specific complications of the two forms of echinococcosis will also help radiologists to discuss the appropriate treatment and management. The aim of this review is to describe the core knowledge that what a radiologist should possess to actively participate in multidisciplinary meetings about hepatic echinococcosis. We discuss the role of imaging, from diagnosis to treatment, in alveolar (AE) and cystic echinococcosis (CE), respectively.