bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term prognosis and clinical course of choking-induced cardiac arrest in patients without the return of spontaneous circulation at hospital arrival: a population-based community study from the Shizuoka Kokuho Database
Authors: Miyoshi Takahiro , Endo Hideki , Yamamoto Hiroyuki , Shimada Koki , Kumamaru Hiraku , Ichihara Nao , Miyachi Yoshiki , Miyata Hiroaki
Published: July 2022

Background

The risk of choking increases with aging, and the number of cases of choking-induced cardiac arrest is increasing. However, few studies have examined the prognosis of choking-induced cardiac arrest. The aim of this study was to reveal the rates of survival and dependence on devices in the long term after choking-induced cardiac arrest.

Methods

We analyzed data from the Shizuoka Kokuho Database, which consists of claims data of approximately 2.2 million people, from April 2012 to September 2018. We selected patients with choking-induced cardiac arrest who received cardiopulmonary resuscitation in the hospital. Patients were excluded if they were less than 20 years old, had an upper airway tumor, received ventilation assistance, or received enteral nutrition in the month prior to cardiac arrest. The primary outcome was death, and the secondary outcomes were the rates of survival at 3-months and independence on devices. Descriptive statistics are presented and compared among age groups (20–64 years, 65–74 years, 75–84 years, 85 years and older), and survival time analysis (Kaplan-Meier method) was performed.

Results

In total, 268 patients were analyzed, including 26 patients in the 20–64 age group, 33 patients in the 65–74 age group, 70 patients in the 75–84 age group, and 139 patients in the ≥85 age group. The overall 3-month survival rate was 5.6% (15/268). The 3-month survival rates were 3.8% (1/26) in the 20–64 age group, 15.2% (5/33) in the 65–74 age group, 8.6% (6/70) in the 75–84 age group, and 2.2% (3/139) in the ≥85 age group. The overall 12-month survival rate was 2.6% (7/268). Of the 7 patients who survived for 12 months, 3 received ventilation management and 5 received tube or intravenous feedings at 3 months. These survivors were still receiving ventilation assistance and tube feedings in the hospital and had not been discharged at 12 months.

Conclusions

The prognosis of choking-induced cardiac arrest was extremely poor when patients were not resuscitated before hospital arrival. Those who survived were mostly dependent on assistive devices. Additionally, none of the survivors dependent on assistive devices had discontinued the use of the devices at the long-term follow-up.
Early use of probiotics might prevent antibiotic-associated diarrhea in elderly (>65 years): a systematic review and meta-analysis
Authors: Zhang Liying , Zeng Xiaofeng , Guo Daxin , Zou Yupei , Gan Huatian , Huang Xiaoli
Published: July 2022

Background

Antibiotic-associated diarrhea (AAD) is diarrhea associated with consuming antibiotics that cannot be explained by other causes. AAD prolongs admission time and increases mortality and financial costs. Elderly individuals are more prone to receive antibiotic treatment and develop AAD. The finding that living probiotic microorganisms decrease AAD incidence in adults (<65 years) has been clarified. However, it is controversial among elderly individuals.

Methods

We aimed to explore whether probiotics could prevent AAD in elderly individuals. We searched three electronic databases (PubMed, EMBASE, and The Cochrane Library), and two reviewers independently screened and assessed the studies. RevMan5.4 software was used to perform a meta-analysis according to the PRISMA guidelines.

Results

Eight RCTs of 4691 participants were included. We excluded two large studies because probiotics were used 48 hours after the first dose of antibiotics, and there was no effect. Subgroup analysis of 6 RCTs showed that probiotics given within two days of antibiotic treatment produced a lower AAD prevalence rate in elderly individuals.

Conclusion

We recommend that elderly individuals could be routinely distributed probiotics to prevent AAD development when receiving antibiotic treatment.

Trial registration

The review was not registered.
PROMPT to improve speech motor abilities in children with cerebral palsy: a wait-list control group trial protocol
Authors: Fiori S. , Ragoni C. , Podda I. , Chilosi A. , Amador C. , Cipriani P. , Guzzetta A. , Sgandurra G.
Published: July 2022

Background

Children with cerebral palsy (CP) often have communication impairments, including speech altered intelligibility. Multiple levels of disrupted speech have been reported in CP, which negatively impact on participation and quality of life, with increase of care needs. Augmentative Alternative Communication (AAC) is an option, with debated benefits and limitations, in particular for its functional use. This is supported by a substantial lack of defined evidences in favor of direct speech articulation intervention in CP. Motor learning-based interventions are effective in CP and are the basis of speech motor interventions such as PROMPT (Prompts for Restructuring Oral Muscular Phonetic Targets). The PROMPT speech motor treatment provides tactile-kinesthetic inputs to facilitate articulatory movements by dynamic modelling, resulting in more efficient motor patterns that can be integrated into speech and communication. In CP, exploratory evidences support the feasibility and preliminarily advantages on intelligibility of motor speech treatments, such as PROMPT, with increased speech motor control, also documented by kinematic analyses.

Methods

A randomized waitlist-control trial will be conducted in children aged between 3- and 10-years having CP and dysarthria (estimated sample size = 60 children). Children will be allocated in the immediate intervention or in the waitlist control group. The intervention consists of an intensive 3 weeks period of twice-a-day administration of PROMPT. Standard care will be administered in the control (waitlist) group. After repeated baseline assessments (T0), the PROMPT treated group will undergo the experimental 3-week intervention period, with T1 assessment at the end. A further T2 assessment will be provided at medium term (3 months after the end of the intervention) for evaluating the stability of intervention. Primary and secondary speech clinical and kinematics outcome measures will be collected at T0, T1 and T2.

Discussion

This paper describes the study protocol consisting of a RCT with two main objectives: (1) to evaluate the or short-term benefits of an intensive speech motor intervention on speech and intelligibility in children with CP and the stability of the intervention at medium term; (2) to describe the kinematic correlates of speech motor control modifications.

Trial registration

Trial registration date 06/12/2019; ClinicalTrials.gov Identifier: NCT04189159.
Targeting autophagy increases the efficacy of proteasome inhibitor treatment in multiple myeloma by induction of apoptosis and activation of JNK
Authors: Salimi Azam , Schroeder Kema Marlen , Schemionek-Reinders Mirle , Vieri Margherita , Maletzke Saskia , Gezer Deniz , Masouleh Behzad Kharabi , Appelmann Iris
Published: July 2022

Background

The therapeutic armamentarium in multiple myeloma has been significantly broadened by proteasome inhibitors, highly efficient means in controlling of multiple myeloma. Despite the developments of therapeutic regimen in treatment of multiple myeloma, still the complete remission requires a novel therapeutic strategy with significant difference in outcomes. Proteasome inhibitors induce autophagy and ER stress, both pivotal pathways for protein homeostasis. Recent studies showed that the IRE1α-XBP1 axis of the unfolded protein response (UPR) is up-regulated in multiple myeloma patients. In addition, XBP1 is crucial for the maintenance of viability of acute lymphoblastic leukemia (ALL).

Results

We analyzed the efficacy of targeting IRE1α-XBP1 axis and autophagy in combination with proteasome inhibitor, ixazomib in treatment of multiple myeloma. In this present study, we first show that targeting the IRE1α-XBP1 axis with small molecule inhibitors (STF-083010, A106) together with the ixazomib induces cell cycle arrest with an additive cytotoxic effect in multiple myeloma. Further, we examined the efficacy of autophagy inhibitors (bafilomycin A, BAF and chloroquine, CQ) together with ixazomib in multiple myeloma and observed that this combination treatment synergistically reduced cell viability in multiple myeloma cell lines (viable cells Ixa: 51.8 ± 3.3, Ixa + BAF: 18.3 ± 7.2, Ixa + CQ: 38.4 ± 3.7) and patient-derived multiple myeloma cells (Ixa: 59.6 ± 4.4, Ixa + CQ: 7.0 ± 2.1). We observed, however, that this combined strategy leads to activation of stress-induced c-Jun N-terminal kinase (JNK). Cytotoxicity mediated by combined proteasome and autophagy inhibition was reversed by addition of the specific JNK inhibitor JNK-In-8 (viable cells: Ixa + BAF: 11.6 ± 7.0, Ixa + BAF + JNK-In-8: 30.9 ± 6.1).

Conclusion

In this study we showed that combined inhibition of autophagy and the proteasome synergistically induces cell death in multiple myeloma. Hence, we consider the implication of pharmaceutical inhibition of autophagy together with proteasome inhibition and UPR-directed therapy as promising novel in vitro treatment strategy against multiple myeloma.
Molecular pathology testing for non-small cell lung cancer: an observational study of elements currently present in request forms and result reports and the opinion of different stakeholders
Authors: Dufraing Kelly , Van Casteren Kaat , Breyne Joke , D’Haene Nicky , Van Campenhout Claude , Vander Borght Sara , Zwaenepoel Karen , Rouleau Etienne , Schuuring Ed , von der Thüsen Jan , Dequeker Elisabeth
Published: July 2022

Background

For patients with non-small cell lung cancer (NSCLC), targeted therapies are becoming part of the standard treatment. It is of question which information the clinicians provide on test requests and how the laboratories adapt test conclusions to this knowledge and regulations.

Methods

This study consisted of two components; 1) checking the presence of pre-defined elements (administrative and key for therapy-choice) on completed requests and corresponding reports in Belgian laboratories, both for tissue- and liquid biopsy (LB)-testing and b) opinion analysis from Belgian pathologists/molecular biologists and clinicians during national pathology/oncology meetings.

Results

Data from 4 out of 6 Belgian laboratories with ISO-accreditation for LB-testing were analyzed, of which 75% were university hospitals. On the scored requests (N = 4), 12 out of 19 ISO-required elements were present for tissue and 11 for LB-testing. Especially relevant patient history, such as line of therapy (for LB), tumor histology and the reason for testing were lacking. Similarly, 11 and 9 out of 18 elements were present in the reports (N = 4) for tissue and LB, respectively.

Elements that pathologists/molecular biologists (N = 18) were missing on the request were the initial activating mutation, previous therapies, a clinical question and testing-related information. For reporting, an item considered important by both groups is the clinical interpretation of the test result. In addition, clinicians (N = 28) indicated that they also wish to read the percentage of neoplastic cells.

Conclusions

Communication flows between the laboratory and the clinician, together with possible pitfalls were identified. Based on the study results, templates for complete requesting and reporting were proposed.
Use of computed tomography-derived body composition to determine the prognosis of patients with primary liver cancer treated with immune checkpoint inhibitors: a retrospective cohort study
Authors: Xiao Lu-shan , Li Rui-ning , Cui Hao , Hong Chang , Huang Chao-yi , Li Qi-mei , Hu Cheng-yi , Dong Zhong-yi , Zhu Hong-bo , Liu Li
Published: July 2022

Background

Immune checkpoint inhibitors (ICIs) have been used to successfully treat primary liver cancer (PLC); however, identifying modifiable patient factors associated with therapeutic benefits is challenging. Obesity is known to be associated with increased survival after ICI treatment; however, the relationship between body composition (muscle, fat) and outcomes is unclear. This study aimed to evaluate the association between sarcopenia and CT-derived fat content and the prognosis of ICIs for the treatment of PLC.

Methods

In this retrospective cohort study of 172 patients with PLC, we measured the skeletal muscle index (SMI), skeletal muscle density, visceral adipose tissue index, subcutaneous adipose tissue index, total adipose tissue index (TATI), and visceral-to-subcutaneous adipose tissue area ratio using CT. In addition, we analyzed the impact of body composition on the prognosis of the patients. Multivariate Cox regression analysis was used to screen for influencing factors.

Results

Among the seven body composition components, low SMI (sarcopenia) and low TATI were significantly associated with poor clinical outcomes. Multivariate analysis revealed that sarcopenia (hazard ratio [HR], 5.39; 95% confidence interval [CI], 1.74–16.74; p = 0.004) was a significant predictor of overall survival (OS). Kaplan–Meier curves showed that sarcopenia and TATI were significant predictors of OS. Body mass index was not associated with survival outcomes.

Conclusions

Sarcopenia and fat tissue content appear to be independently associated with reduced survival rates in patients with PLC treated with ICIs.
Modeling relationships between iron status, behavior, and brain electrophysiology: evidence from a randomized study involving a biofortified grain in Indian adolescents
Authors: Wenger Michael J. , Murray Kolb Laura E. , Scott Samuel P. , Boy Erick , Haas Jere D.
Published: July 2022

Background

Iron deficiency (ID) and iron deficiency anemia (IDA) are highly-prevalent nutrient deficiencies and have been shown to have a range of negative effects on cognition and brain function. Human intervention studies including measures at three levels—blood, brain, and behavior—are rare and our objective was to model the relationships among measures at these three levels in school-going Indian adolescents.

Methods

Male and female adolescents in rural India were screened for ID/IDA. Subjects consumed 2 meals/day for 6 months; half were randomly assigned to consume meals made from a standard grain (pearl millet) and half consumed meals made from an iron biofortified pearl millet (BPM). Prior to and then at the conclusion of the feeding trial, they completed a set of cognitive tests with concurrent electroencephalography (EEG).

Results

Overall, serum ferritin (sFt) levels improved over the course of the study. Ten of 21 possible measures of cognition showed improvements from baseline (BL) to endline (EL) that were larger for those consuming BPM than for those consuming the comparison pearl millet (CPM). Critically, the best model for the relationship between change in iron status and change in cognition had change in brain measures as a mediating factor, with both change in serum ferritin as a primary predictor and change in hemoglobin as a moderator.

Conclusions

A dietary intervention involving a biofortified staple grain was shown to be efficacious in improving blood iron biomarkers, behavioral measures of cognition, and EEG measures of brain function. Modeling the relationships among these variables strongly suggests multiple mechanisms by which blood iron level affects brain function and cognition.

Trial registration

Registered at ClinicalTrials.gov,NCT02152150, 02 June 2014.
Reconstruction of the coracoclavicular ligament with palmaris longus tendon and Mersilene tape for acromioclavicular dislocations
Authors: Lee Yoon-Min , Yeo Joo Dong , Hwang Zin Ouk , Song Seok-Whan , Sur Yoo Joon
Published: July 2022

Background

Acromioclavicular (AC) joint dislocation is common among shoulder injuries, and various surgical methods have been introduced for effective ligament reconstruction. Reconstruction of the coracoclavicular (CC) ligament in the anatomical position using autologous tendons is a recent surgical trend. This study is to report clinical and radiologic results of reconstruction of the CC ligament using an autologous palmaris longus tendon interweaved with Mersilene tape (PLMT) with a minimum 2-year follow-up.

Methods

This retrospective study analyzed 76 patients (mean age, 43.4 ± 11.2 years) with AC joint dislocation treated by reconstruction of the CC ligament with PLMT, from March 2004 to February 2017. The mean follow-up period was 28 ± 6.7 months (range, 24–66 months). The Visual Analog Scale (VAS) for pain assessment, American Shoulder and Elbow Surgeons rating scale (ASES), and Constant Score (CS) were used to evaluate clinical outcomes at the preoperative and the final follow-ups. CC and AC distances were measured using anteroposterior (AP) X-ray preoperatively and at the final follow-up for radiologic outcomes. Complications were also assessed.

Results

The mean preoperative VAS for pain, ASES, CS were 5.7 ± 0.7, 77.1 ± 6.2, and 61.5 ± 5.2, respectively. These scores at the final follow-up improved to 2.1 ± 0.5, 90.9 ± 4.3, and 94 ± 7.0, respectively (p = 0.043, p <  0.001, p <  0.001). The mean preoperative CC and AC distances were 16.49 ± 3.73 mm and 13.84 ± 3.98 mm, respectively. The final follow-up CC and AC distances were 9.29 ± 2.72 mm and 5.30 ± 2.09 mm, respectively (p <  0.001, p <  0.001). Although a slight re-widening of the CC distance occurred in 10 patients (13.1%), most patients regained full range of motion of the affected shoulder at the final follow-up.

Conclusion

The CC ligament reconstruction with PLMT for the treatment of AC joint dislocation showed good clinical and radiological results. This technique could be a good alternative treatment for AC dislocations.
Total hip arthroplasty after rotational acetabular osteotomy for developmental dysplasia of the hip: a retrospective observational study
Authors: Negayama Takahiro , Iwata Ken , Shimamura Masashi , Senda Teppei , Mashiba Tasuku , Kaji Yoshio , Yamamoto Tetsuji
Published: July 2022

Background

Total hip arthroplasty after osteotomy is more technically challenging than primary total hip arthroplasty, especially concerning cup placement. This is attributed to bone morphological abnormalities caused by acetabular bone loss and osteophyte formation. This study aimed to investigate the clinical and radiological outcomes of total hip arthroplasty after rotational acetabular osteotomy compared with those of primary total hip arthroplasty, focusing mainly on acetabular deformity and cup position.

Methods

The study included 22 hips that had undergone rotational acetabular osteotomy and 22 hips in an age- and sex-matched control group of patients who underwent total hip arthroplasties between 2005 and 2020. We analyzed cup abduction and anteversion; lateral, anterior, and posterior cup center–edge angle; hip joint center position; femoral anteversion angle; and presence of acetabular defect using postoperative radiography and computed tomography. Operative results and clinical evaluations were also analyzed.

Results

The clinical evaluation showed that the postoperative flexion range of motion was lower in total hip arthroplasty after rotational acetabular osteotomy than in primary total hip arthroplasty, although no significant difference was noted in the postoperative total Japanese Orthopedic Association hip score. The operative time was significantly longer in the rotational acetabular osteotomy group than in the control group, but there was no significant difference in blood loss. The lateral cup center–edge angle was significantly higher and the posterior cup center–edge angle was significantly lower in the total hip arthroplasty after rotational acetabular osteotomy, suggesting a posterior bone defect existed in the acetabulum. In total hip arthroplasty after rotational acetabular osteotomy, the hip joint center was located significantly superior and lateral to the primary total hip arthroplasty.

Conclusions

In total hip arthroplasty after rotational acetabular osteotomy, the cup tended to be placed in the superior and lateral positions, where there was more bone volume. The deformity of the acetabulum and the high hip center should be considered for treatment success because they may cause cup instability, limited range of motion, and impingement.
Activity limitation and participation restriction in Osteoarthritis and Rheumatoid arthritis: findings based on the National Health and Nutritional Examination Survey
Authors: Gikaro John Marwa , Xiong Hao , Lin Feng
Published: July 2022

Background

Osteoarthritis (OA) and Rheumatoid arthritis (RA) are the most common joint diseases leading to chronic pain and disability. Given the chronicity and disabling nature of OA and RA, they are likely to influence full participation of individuals in the society. An activity limitation occurs when a person has difficulty executing an activity; a participation restriction is experienced when a person has difficulty participating in a real-life situation. The aim of this study was to examine the associations between OA and RA and the domains of activity limitation and participation restriction.

Methods

A cross-sectional study design comprised 3604 adults from the 2009 to 2018 National Health and Nutrition Examination Survey (NHANES). All participants aged ≥ 20 years with complete data were included. Activity limitation and participation restriction were assessed by reported difficulty in performing 14 tasks selected from Physical Functioning Questionnaire. Data on OA and RA were obtained from Medical Conditions Questionnaire. Weighted logistic regression model was used to examine the associations between OA and RA and the selected tasks.

Results

Over 36% of participants had limitations. Both OA (OR = 2.11) and RA (OR = 2.36) were positively associated with activity limitation and participation restriction (p < 0.001). Poor or fair health was associated with difficulty in physical functioning, with highest odds observed in leisure activities (OR = 2.05), followed by difficulty in attending social events (OR = 1.99), walking for a quarter mile (OR = 1.97), preparing meals (OR = 1.93) and walking up ten steps (OR = 1.92).

Conclusion

Adults with OA and RA had nearly similar odds of having activity limitations and participation restrictions. Difficulty in executing most activities of daily living (ADLs) has significant association with poor or fair health. Holistic interdisciplinary care to individuals with OA or RA focusing on ADLs and environmental factors may improve health status.
Is sentinel lymph node biopsy without frozen section in early stage breast cancer sufficient in accordance with ACOSOG-Z0011? A retrospective review from King Chulalongkorn Memorial Hospital
Authors: Treeratanapun Nattanan , Lerttiendamrong Bhoowit , Vacharathit Voranaddha , Tantiphlachiva Kasaya , Vongwattanakit Phuphat , Manasnayakorn Sopark , Vongsaisuwon Mawin
Published: July 2022

Background

In 2021, there is an increased global trend for sending sentinel lymph node biopsy (SLNB) specimens for permanent section (PS) without intraoperative frozen sections (FS). This pilot study conducted in Thailand determines the re-operation rate for SLNB without FS.

Method

We retrospectively reviewed 239 SLNB cases without FS at King Chulalongkorn Memorial Hospital from April 2016 to April 2021. The patients were diagnosed with primary invasive breast cancer with clinically negative nodes. The clinical nodal status was assessed from physical examination. The re-operation rate was determined by the number of positive SLNs; where 3 more nodal metastases were subjected to a second surgical procedure.

Result

Between April 2016 and April 2021, 239 patients who had undergone SLNB in accordance with ACOSOG Z0011 criteria with PS alone was enrolled. A total of 975 SLNs were removed from these 239 patients, with an average of 4.15 nodes per patient. Out of 239 patients, 21 (8.8%) and 6 (2.5%) had metastatic disease in 1 and 2 nodes, respectively. The remaining 212 (88.7%) patients had no nodal metastasis. None of the patients were subjected to a second surgical procedure.

Conclusion

We conclude that the implementation of SLNB with PS analysis alone in patients who satisfy the ACOSOG Z0011 criteria, with a re-operation rate of 0%, does not have outcomes that would be altered by the standard of care additional FS analysis. With ommision of FS analysis, operation cost, operative time and anesthetic side effects are projected to decrease.
Clinical features and recurrence of Corynebacterium kroppenstedtii infection in patients with mastitis
Authors: Zeng Weiwei , Lao Sixian , Jia Wenbin , Shen Xintian , Wu Lijuan , Zhong Yan , Wang Feiling , Zhong Guoping
Published: July 2022

Background

Few studies have investigated the differences in clinical features of patients with mastitis following Corynebacterium kroppenstedtii infection, and most focused on the bacterial antimicrobial susceptibility, detection methods and therapy.

Methodology

There were 133 patients with mastitis infected by C. kroppenstedtii between August 2016 and September 2019. C. kroppenstedtii was identified using mass spectrometry. The demographics, clinical diagnosis, laboratory test results of different types of mastitis combined with bacillus infection, and the effects of different treatments in reducing recurrence were compared.

Results

The incidence of pus following C. kroppenstedtii infection was higher in patients with non-granulomatous lobular mastitis (NGLM; 56.6%) than in those with granulomatous lobular mastitis (GLM; 33.3%; χ2 = 7.072, p = 0.008). While C-reactive protein (CRP) was higher in the GLM group (12.50 mg/L) than in the NGLM group (6.05 mg/L; Z =  − 2.187, p = 0.029). Treatment with local lavage (triamcinolone acetonide) and antibiotics (cefuroxime) showed a recurrent rate of 25.9% in C. kroppenstedtii infection.

Conclusion

Increased pus, large masses, and an elevated CRP level may occur in patients with mastitis infected by C.kroppenstedtii. These clinical features may guide the determination of the bacterial infection in patients with mastitis. Combining an antibiotic with a triamcinolone acetonide lavage, preferably cefuroxime, may reduce the recurrence.
A randomised controlled trial on the effects of a structural education module among women with polycystic ovarian syndrome on nutrition and physical activity changes
Authors: Dashti Sareh , Abdul Hamid Habibah , Mohamad Saini Suriani , Tusimin Maiza , Ismail Maimunah , Jafarzadeh Esfehani Ali , Ching Siew Mooi , Lee Kai Wei , Ismail Norzian , Wong Jie Lin , Abdul Latiff Latiffah
Published: July 2022

Background

Polycystic ovarian syndrome (PCOS) is a complex metabolic, endocrine and reproductive disorder that has a huge impact on the life of women. To ascertain the effectiveness of health education module among women with PCOS.

Methods

This single-centre, randomised controlled trial was conducted on female staff of the University Putra Malaysia who were diagnosed with PCOS. Subjects were randomly assigned into intervention (n = 34) and control group (n = 35). In the intervention group, they need to take part in 8 education sessions in total over 6 months, and feedback was collected at the end of the session.

Results

Primary outcome was changes in knowledge, attitude and practise of nutrition. Secondary outcomes were eating attitude and behaviour as well as knowledge, attitude and practise towards physical activity. After 6-months of intervention, there was a significant difference observed in nutrition knowledge 1 score (p < 0.001) and nutrition knowledge 2 score (p = 0.01) between intervention and control groups. Similarly, there was a significant difference observed in international physical activity questionnaire score (p = 0.02) between intervention and control groups. However there was no significant changes for attitude and practice of nutrition, eating attitude as well as knowledge, attitude and practise of physical activity.

Conclusions

Our study showed that 6-months of education intervention can improve nutrition and physical activity knowledge. Based on this study, the education module may be considered an effective intervention for women with PCOS.

Trial registration: Name of the registry: Australian New Zealand Clinical Trials Registry (ANZCTR). Trial registration number: ACTRN12617000135314. Date of registration: 24/01/2017. URL of trial registry record: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372037
Use of machine learning to identify patients at risk of sub-optimal adherence: study based on real-world data from 10,929 children using a connected auto-injector device
Authors: Spataru Amalia , van Dommelen Paula , Arnaud Lilian , Le Masne Quentin , Quarteroni Silvia , Koledova Ekaterina
Published: July 2022

Background

Our aim was to develop a machine learning model, using real-world data captured from a connected auto-injector device and from early indicators from the first 3 months of treatment, to predict sub-optimal adherence to recombinant human growth hormone (r-hGH) in patients with growth disorders.

Methods

Adherence to r-hGH treatment was assessed in children (aged < 18 years) who started using a connected auto-injector device (easypod™), and transmitted injection data for ≥ 12 months. Adherence in the following 3, 6, or 9 months after treatment start was categorized as optimal (≥ 85%) versus sub-optimal (< 85%). Logistic regression and tree-based models were applied.

Results

Data from 10,929 children showed that a random forest model with mean and standard deviation of adherence over the first 3 months, infrequent transmission of data, not changing certain comfort settings, and starting treatment at an older age was important in predicting the risk of sub-optimal adherence in the following 3, 6, or 9 months. Sensitivities ranged between 0.72 and 0.77, and specificities between 0.80 and 0.81.

Conclusions

To the authors’ knowledge, this is the first attempt to integrate a machine learning model into a digital health ecosystem to help healthcare providers to identify patients at risk of sub-optimal adherence to r-hGH in the following 3, 6, or 9 months. This information, together with patient-specific indicators of sub-optimal adherence, can be used to provide support to at-risk patients and their caregivers to achieve optimal adherence and, subsequently, improve clinical outcomes.
Evidence for close molecular proximity between reverting and undifferentiated cells
Authors: Zreika Souad , Fourneaux Camille , Vallin Elodie , Modolo Laurent , Seraphin Rémi , Moussy Alice , Ventre Elias , Bouvier Matteo , Ozier-Lafontaine Anthony , Bonnaffoux Arnaud , Picard Franck , Gandrillon Olivier , Gonin-Giraud Sandrine
Published: July 2022

Background

According to Waddington’s epigenetic landscape concept, the differentiation process can be illustrated by a cell akin to a ball rolling down from the top of a hill (proliferation state) and crossing furrows before stopping in basins or “attractor states” to reach its stable differentiated state. However, it is now clear that some committed cells can retain a certain degree of plasticity and reacquire phenotypical characteristics of a more pluripotent cell state. In line with this dynamic model, we have previously shown that differentiating cells (chicken erythrocytic progenitors (T2EC)) retain for 24 h the ability to self-renew when transferred back in self-renewal conditions. Despite those intriguing and promising results, the underlying molecular state of those “reverting” cells remains unexplored. The aim of the present study was therefore to molecularly characterize the T2EC reversion process by combining advanced statistical tools to make the most of single-cell transcriptomic data. For this purpose, T2EC, initially maintained in a self-renewal medium (0H), were induced to differentiate for 24H (24H differentiating cells); then, a part of these cells was transferred back to the self-renewal medium (48H reverting cells) and the other part was maintained in the differentiation medium for another 24H (48H differentiating cells). For each time point, cell transcriptomes were generated using scRT-qPCR and scRNAseq.

Results

Our results showed a strong overlap between 0H and 48H reverting cells when applying dimensional reduction. Moreover, the statistical comparison of cell distributions and differential expression analysis indicated no significant differences between these two cell groups. Interestingly, gene pattern distributions highlighted that, while 48H reverting cells have gene expression pattern more similar to 0H cells, they are not completely identical, which suggest that for some genes a longer delay may be required for the cells to fully recover. Finally, sparse PLS (sparse partial least square) analysis showed that only the expression of 3 genes discriminates 48H reverting and 0H cells.

Conclusions

Altogether, we show that reverting cells return to an earlier molecular state almost identical to undifferentiated cells and demonstrate a previously undocumented physiological and molecular plasticity during the differentiation process, which most likely results from the dynamic behavior of the underlying molecular network.
The health impacts of Indonesian peatland fires
Authors: Hein Lars , Spadaro Joseph V. , Ostro Bart , Hammer Melanie , Sumarga Elham , Salmayenti Resti , Boer Rizaldi , Tata Hesti , Atmoko Dwi , Castañeda Juan-Pablo
Published: July 2022

Background

Indonesian peatlands have been drained for agricultural development for several decades. This development has made a major contribution to economic development. At the same time, peatland drainage is causing significant air pollution resulting from peatland fires. Peatland fires occur every year, even though their extent is much larger in dry (El Niño) years. We examine the health effects of long-term exposure to fine particles (PM2.5) from all types of peatland fires (including the burning of above and below ground biomass) in Sumatra and Kalimantan, where most peatland fires in Indonesia take place.

Methods

We derive PM2.5 concentrations from satellite imagery calibrated and validated with Indonesian Government data on air pollution, and link increases in these concentrations to peatland fires, as observed in satellite imagery. Subsequently, we apply available epidemiological studies to relate PM2.5 exposure to a range of health outcomes. The model utilizes the age distribution and disease prevalence of the impacted population.

Results

We find that PM2.5 air pollution from peatland fires, causes, on average, around 33,100 adults and 2900 infants to die prematurely each year from air pollution. In addition, peatland fires cause on average around 4390 additional hospitalizations related to respiratory diseases, 635,000 severe cases of asthma in children, and 8.9 million lost workdays. The majority of these impacts occur in Sumatra because of its much higher population density compared to Kalimantan. A main source of uncertainty is in the Concentration Response Functions (CRFs) that we use, with different CRFs leading to annual premature adult mortality ranging from 19,900 to 64,800 deaths. Currently, the population of both regions is relatively young. With aging of the population over time, vulnerabilities to air pollution and health effects from peatland fires will increase.

Conclusions

Peatland fire health impacts provide a further argument to combat fires in peatlands, and gradually transition to peatland management models that do not require drainage and are therefore not prone to fire risks.
A universal strategy for the fabrication of single-photon and multiphoton NIR nanoparticles by loading organic dyes into water-soluble polymer nanosponges
Authors: Yang Li-Xing , Liu Yu-Cheng , Cho Chang-Hui , Chen Yi-Rou , Yang Chan-Shan , Lu Yin-Lin , Zhang Zhiming , Tsai Yi-Tseng , Chin Yu-Cheng , Yu Jiashing , Pan Hsiu-Min , Jiang Wei-Rou , Chia Zi-Chun , Huang Wei-Shiang , Chiu Yu-Lin , Sun Chun-Kai , Huang Yu-Ting , Chen Li-Ming , Wong Ken-Tsung , Huang Han-Min , Chen Chih-Hsin , Chang Yuan Jay , Huang Chih-Chia , Liu Tzu-Ming
Published: July 2022

The development of optical organic nanoparticles (NPs) is desirable and widely studied. However, most organic dyes are water-insoluble such that the derivatization and modification of these dyes are difficult. Herein, we demonstrated a simple platform for the fabrication of organic NPs designed with emissive properties by loading ten different organic dyes (molar masses of 479.1–1081.7 g/mol) into water-soluble polymer nanosponges composed of poly(styrene-alt-maleic acid) (PSMA). The result showed a substantial improvement over the loading of commercial dyes (3.7–50% loading) while preventing their spontaneous aggregation in aqueous solutions. This packaging strategy includes our newly synthesized organic dyes (> 85% loading) designed for OPVs (242), DSSCs (YI-1, YI-3, YI-8), and OLEDs (ADF-1–3, and DTDPTID) applications. These low-cytotoxicity organic NPs exhibited tunable fluorescence from visible to near-infrared (NIR) emission for cellular imaging and biological tracking in vivo. Moreover, PSMA NPs loaded with designed NIR-dyes were fabricated, and photodynamic therapy with these dye-loaded PSMA NPs for the photolysis of cancer cells was achieved when coupled with 808 nm laser excitation. Indeed, our work demonstrates a facile approach for increasing the biocompatibility and stability of organic dyes by loading them into water-soluble polymer-based carriers, providing a new perspective of organic optoelectronic materials in biomedical theranostic applications.
IGF1 receptor-targeted black TiO2 nanoprobes for MRI-guided synergetic photothermal-chemotherapy in drug resistant pancreatic tumor
Authors: Xu Kaiwei , Jin Lufei , Xu Liu , Zhu Yuchao , Hong Lu , Pan Chunshu , Li Yanying , Yao Junlie , Zou Ruifen , Tang Weiwei , Wang Jianhua , Wu Aiguo , Ren Wenzhi
Published: July 2022

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest malignant tumors with features of matrix barrier caused poor drug permeability, and susceptibility to drug resistance. Herein, a PDAC and its stromal cell dual-targeted photothermal-chemotherapy strategy is explored to loosen the matrix and reverse drug resistance. To achieve this goal, black TiO2-Gd nanocomposites were conjugated with insulin like growth factor 1 (IGF1), and loaded with gemcitabine (GEM) to construct bTiO2-Gd-IGF1-GEM nanoprobes. In vitro results show that under 808 nm near-infrared irradiation, killing effect of the nanoprobes on drug-resistant MIA PaCa-2 cell is 3.3 times than that of GEM alone. In vivo experiments indicate the synergetic photothermal-chemotherapy not only loosens fibrous matrix of pancreatic tumor model, but also dramatically inhibits tumor growth, and almost completely eradicates the tumor after 12 days of treatment. In addition, relaxation rate of the nanoprobes is 8.2 times than commercial contrast agent Magnevist, therefore boosts the signal of magnetic resonance imaging in pancreatic tumor. In conclusion, our results reinforce that the prepared nanoprobes are promising to break matrix barrier and overcome drug resistance in PDAC.
The role of interleukin‑7 serum level as biological marker in breast cancer: a cross‑sectional, observational, and analytical study
Authors: Sermaxhaj Faton , Dedić Plavetić Natalija , Gozalan Ugur , Kulić Ana , Radmilović Varga Ljubica , Popović Marina , Sović Slavica , Mijatović Davor , Sermaxhaj Besim , Sopjani Mentor
Published: July 2022

Background

The important role that the immune system plays in malignant diseases is well known. The action of interleukin-7 (IL-7) as a cytokine has been observed in many cellular processes, both in normal cells of the immune system and in some cancer cells. The aim of this study has been to explore whether there is any elevation of interleukin-7 serum levels in early invasive breast cancer (EIBC) patients in comparison with healthy controls. In addition, the correlation between the IL-7 serum level and the histopathological characteristics of the tumor has been evaluated.

Methods

This cross-sectional, observational, and analytical study included 213 consecutive patients with EIBC (113 from Croatia and 100 from Kosovo) and 62 healthy participants as the control group (30 from Croatia and 32 from Kosovo). Blood samples have been taken from patients confirmed with breast cancer (BC) by biopsy, prior to surgical intervention and other oncological treatments, as well as from healthy participants. A serum IL-7 level has been measured, using the “Sandwich” ELISA Immunoenzyme test. In addition, after the surgical intervention, histopathological specimen examinations and immunohistochemistry have been performed and analyzed. The differences in the distribution of the numerical variables have been analyzed with the Mann–Whitney U test and Kruskal–Wallis ANOVA test. Correlations have been tested with Pearson coefficients. A P-value < 0.05 has been accepted as statistically significant.

Results

The serum level of IL-7 in EIBC patients was significantly higher than in control cases (P 0.001). Patients with invasive lobular carcinoma (ILC) seem to have a lower IL-7 serum level compared to other histological subtypes, and the difference has been significant (P = 0.043). There has been no correlation between IL-7 serum level and histopathological characteristics of the tumor, with neither age nor menopausal status of the patients.

Conclusions

Noting the significant increase in the IL-7 serum level in the EIBC patients as compared to the healthy control group, the use of IL-7 as a potential diagnostic indicator for BC, as well as in the follow-up of the patients after treatment, can be assumed. The lack of correlation with tumor size, lymph node metastasis, and all other histopathological characteristics of the tumor questions its use as a prognostic indicator.
Molecular dissection of a hyper-aggressive CBFB-MYH11/FLT3-ITD–positive acute myeloid leukemia
Authors: Lo Iudice Gabriele , De Bellis Eleonora , Savi Arianna , Guarnera Luca , Massacci Alice , De Nicola Francesca , Goeman Frauke , Ottone Tiziana , Divona Mariadomenica , Pallocca Matteo , Fanciulli Maurizio , Voso Maria Teresa , Ciliberto Gennaro
Published: July 2022

Acute Myeloid Leukaemia (AML) is a haematological malignancy showing a hypervariable landscape of clinical outcomes and phenotypic differences, explainable by heterogeneity at the cellular and molecular level. Among the most common genomic alterations,CBFB-MYH11rearrangement andFLT3-ITD gene mutations, have opposite clinical significance and are unfrequently associated. We present here a Molecular Case Report in which these two events co-exist an ultra-aggressive phenotype resulting in death in 4 days from hospital admittance. Somatic and germline Whole Exome Sequencing analysis was performed to uncover other putative driver mutations, de-novo genomic structural events or germline clusters increasing cancer insurgence. Only three mutations inLTK,BCAS2andLGAS9were found, unlikely causative of the exhibited phenotype, prompting to additional investigation of the rareCBFB-MYH11/ FLT3-ITD scenario.
Syringin exerts anti-breast cancer effects through PI3K-AKT and EGFR-RAS-RAF pathways
Authors: Wang Fei , Yuan Chong , Liu Bo , Yang Yan-Fang , Wu He-Zhen
Published: July 2022

Background

Breast cancer (BC) is one of the most common malignant tumors with the highest mortality in the world. Modern pharmacological studies have shown that Syringin has an inhibitory effect on many tumors, but its anti-BC efficacy and mechanism are still unclear.

Methods

First, Syringin was isolated from Acanthopanax senticosus (Rupr. & Maxim.) Harms (ASH) by systematic solvent extraction and silica gel chromatography column. The plant name is composed of genus epithet, species additive words and the persons’ name who give its name. Then, the hub targets of Syringin against BC were revealed by bioinformatics. To provide a more experimental basis for later research, the hub genes which could be candidate biomarkers of BC and a ceRNA network related to them were obtained. And the potential mechanism of Syringin against BC was proved in vitro experiments.

Results

Syringin was obtained by liquid chromatography-mass spectrometry (LC–MS), nuclear magnetic resonance (NMR), and high-performance liquid chromatography (HPLC). Bioinformatics results showed that MAP2K1, PIK3CA, HRAS, EGFR, Caspase3, and PTGS2 were the hub targets of Syringin against BC. And PIK3CA and HRAS were related to the survival and prognosis of BC patients, the PIK3CA-hsa-mir-139-5p-LINC01278 and PIK3CA-hsa-mir-375 pathways might be closely related to the mechanism of Syringin against BC. In vitro experiments confirmed that Syringin inhibited the proliferation and migration and promoted apoptosis of BC cells through the above hub targets.

Conclusions

Syringin against BC via PI3K-AKT-PTGS2 and EGFR-RAS-RAF-MEK-ERK pathways, and PIK3CA and HRAS are hub genes for adjuvant treatment of BC.

Graphical Abstract
Identification of functional pathways and molecular signatures in neuroendocrine neoplasms by multi-omics analysis
Authors: Melone Viola , Salvati Annamaria , Palumbo Domenico , Giurato Giorgio , Nassa Giovanni , Rizzo Francesca , Palo Luigi , Giordano Alessandro , Incoronato Mariarosaria , Vitale Mario , Mian Caterina , Di Biase Immacolata , Cristiano Stefano , Narciso Viviana , Cantile Monica , Di Mauro Annabella , Tatangelo Fabiana , Tafuto Salvatore , Modica Roberta , Pivonello Claudia , Salvatore Marco , Colao Annamaria , Weisz Alessandro , Tarallo Roberta
Published: July 2022

Background

Neuroendocrine neoplasms (NENs) represent a heterogeneous class of rare tumors with increasing incidence. They are characterized by the ability to secrete peptide hormones and biogenic amines but other reliable biomarkers are lacking, making diagnosis and identification of the primary site very challenging. While in some NENs, such as the pancreatic ones, next generation sequencing technologies allowed the identification of new molecular hallmarks, our knowledge of the molecular profile of NENs from other anatomical sites is still poor.

Methods

Starting from the concept that NENs from different organs may be clinically and genetically correlated, we applied a multi-omics approach by combining multigene panel testing, CGH-array, transcriptome and miRNome profiling and computational analyses, with the aim to highlight common molecular and functional signatures of gastroenteropancreatic (GEP)-NENs and medullary thyroid carcinomas (MTCs) that could aid diagnosis, prognosis and therapy.

Results

By comparing genomic and transcriptional profiles, ATM-dependent signaling emerged among the most significant pathways at multiple levels, involving gene variations and miRNA-mediated regulation, thus representing a novel putative druggable pathway in these cancer types. Moreover, a set of circulating miRNAs was also selected as possible diagnostic/prognostic biomarkers useful for clinical management of NENs.

Conclusions

These findings depict a complex molecular and functional landscape of NENs, shedding light on novel therapeutic targets and disease biomarkers to be exploited.