bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Infant Health Study - Promoting mental health and healthy weight through sensitive parenting to infants with cognitive, emotional, and regulatory vulnerabilities: protocol for a stepped-wedge cluster-randomized trial and a process evaluation within municipality settings
Authors: Skovgaard Anne Mette , Bakermans-Kranenburg Marian , Pontoppidan Maiken , Tjørnhøj-Thomsen Tine , Madsen Katrine Rich , Voss Ida , Wehner Stine Kjær , Pedersen Trine Pagh , Finseth Lotte , Taylor Rodney S. , Tolstrup Janne Schurmann , Ammitzbøll Janni 
Published: January 2022

AbstractBackgroundChild mental health problems are a major public health concern associated with poor mental and physical health later in development. The study evaluates a new community-based intervention to promote sensitive parenting and reduce enduring mental health problems and unhealthy weight among vulnerable infants aged 9-24 months.MethodsWe use a step-wedge cluster randomized controlled trial design conducted within a home visiting program offered by community health nurses to infant families in Denmark. Sixteen municipalities are randomly allocated to implement the intervention starting at three successive time points from May 1, 2022 to January 1, 2023. A total of 900-1000 families will be included. A standardized program, Psykisk Udvikling og Funktion (PUF), is used to identify infants with major problems of eating, sleep, emotional or behavioral regulation or developmental problems. The intervention builds on the Video-Feedback Intervention to Promote Positive Parenting (VIPP) program, adapted to the PUF-context and named the VIPP-PUF. Children will be followed up at ages 18 and 24 months. Primary outcome measure is the Strengths and Difficulties Questionnaire (SDQ) at child age 24 months. The other outcome measures include body mass index z-scores, the Ages and Stages Questionnaire Social-Emotional (ASQ:SE2); the Child Behavior Checklist (CBCL 1½ -5); Eating behavior Questionnaires; the Being a Mother-questionnaire (BaM13); the Parental Stress Scale (PSS); and the WHO-5 well-being index (WHO-5). Data on child and family factors are obtained from National registries and the Child Health Database.Quantitative measures are applied to examine the effectiveness of the VIPP-PUF intervention and the implementation process. Qualitative measures include interviews with CHNs, parents and municipality stakeholders to explore factors that may influence the adherence and effectiveness of the intervention.DiscussionThe study examines a service-setting based intervention building on the promotion of sensitive parenting to vulnerable infants. We use a mixed methods approach to evaluate the intervention, taking into account the influences of COVID-19 pandemic running since March 2020. Overall, the study has potential to add to the knowledge on the possibilities of prevention within the municipality child health care to reduce the risk of mental health problems and unhealthy weight in early childhood.Trial registrationwww.ClinicalTrials.gov; IDNCT04601779; Protocol ID 95-110-21307. Registered 25 June 2021.
A rare combination of tumor-induced osteomalacia caused by sinonasal glomangiopericytoma and coexisting parathyroid adenoma: case report and literature review
Authors: Brociek-Piłczyńska Agnieszka , Brodowska-Kania Dorota , Szczygielski Kornel , Lorent Małgorzata , Zieliński Grzegorz , Kowalewski Piotr , Jurkiewicz Dariusz 
Published: January 2022

Abstract
Background
Tumor-induced osteomalacia (TIO) is a rare, acquired disease of renal phosphate wasting and disturbed vitamin D homeostasis as a result of the action of a phosphaturic protein – FGF-23, produced by a neoplasm. Although the clinical and biochemical profile of the syndrome is characteristic, it remains underreported and unrecognized by clinicians. Hyperparathyroidism is rarely associated with oncogenic osteomalacia, but it should be considered because of potentially life-threatening hypophosphatemia caused by both conditions.

Case presentation
We report a case of a 42-year-old woman admitted to the Department of Otolaryngology of the Military Institute of Medicine in Warsaw for the endoscopic resection of hormonally active glomangiopericytoma extending into the anterior skull base. She presented with a 5-year history of musculoskeletal pain and progressive weakness of the extremities which finally led her to become bedridden. After the excision of the tumor her symptoms and laboratory results gradually improved except increasing PTH serum levels. Further examination revealed a parathyroid proliferative tumor, which was surgically removed. The patient walked without aids at follow-up 16 months after the surgery.

Conclusions
This case is unusual because of tumor-induced osteomalacia and parathyroid adenoma occurring concomitantly. Further investigations of FGF-23 and PTH interplay should be conducted to elucidate the pathogenesis of hyperparathyroidism and tumorigenesis in some cases of TIO. By presenting this case, we wanted to remind clinicians of a rare and misdiagnosed paraneoplastic syndrome and highlight the importance of monitoring PTH concentrations during the follow-up of patients with TIO.
Insights into N6-methyladenosine and programmed cell death in cancer
Authors: Liu Li , Li Hui , Hu Dingyu , Wang Yanyan , Shao Wenjun , Zhong Jing , Yang Shudong , Liu Jing , Zhang Ji 
Published: January 2022

AbstractN6-methyladenosine (m6A) methylation, the most common form of internal RNA modification in eukaryotes, has gained increasing attention and become a hot research topic in recent years. M6A plays multifunctional roles in normal and abnormal biological processes, and its role may vary greatly depending on the position of the m6A motif. Programmed cell death (PCD) includes apoptosis, autophagy, pyroptosis, necroptosis and ferroptosis, most of which involve the breakdown of the plasma membrane. Based on the implications of m6A methylation on PCD, the regulators and functional roles of m6A methylation were comprehensively studied and reported. In this review, we focus on the high-complexity links between m6A and different types of PCD pathways, which are then closely associated with the initiation, progression and resistance of cancer. Herein, clarifying the relationship between m6A and PCD is of great significance to provide novel strategies for cancer treatment, and has a great potential prospect of clinical application.
Quantitative metabolic analysis of plasma extracellular vesicles for the diagnosis of severe acute pancreatitis
Authors: Lou Doudou , Shi Keqing , Li Hui-Ping , Zhu Qingfu , Hu Liang , Luo Jiaxin , Yang Rui , Liu Fei 
Published: January 2022

Abstract
Background
Severe acute pancreatitis (SAP) is the most common gastrointestinal disease and is associated with unpredictable seizures and high mortality rates. Despite improvements in the treatment of acute pancreatitis, the timely and accurate diagnosis of SAP remains highly challenging. Previous research has shown that extracellular vesicles (EVs) in the plasma have significant potential for the diagnosis of SAP since the pancreas can release EVs that carry pathological information into the peripheral blood in the very early stages of the disease. However, we know very little about the metabolites of EVs that might play a role in the diagnosis of SAP.

Methods
Here, we performed quantitative metabolomic analyses to investigate the metabolite profiles of EVs isolated from SAP plasma. We also determined the metabolic differences of EVs when compared between healthy controls, patients with SAP, and those with mild acute pancreatitis (MAP).

Results
A total of 313 metabolites were detected, mainly including organic acids, amino acids, fatty acids, and bile acids. The results showed that the metabolic composition of EVs derived from SAP and MAP was significantly different from those derived from healthy controls and identified specific differences between EVs derived from patients with SAP and MAP. On this basis, we identified four biomarkers from plasma EVs for SAP detection, including eicosatrienoic acid (C20:3), thiamine triphosphate, 2-Acetylfuran, and cis-Citral. The area under the curve (AUC) was greater than 0.95 for both discovery (n = 30) and validation (n = 70) sets.

Conclusions
Our data indicate that metabolic profiling analysis of plasma EVs and the screening of potential biomarkers are of significant potential for improving the early diagnosis and severity differentiation of acute pancreatitis.

Graphical abstract
Application of workload indicators to assess the allocation of orthopedists in a national referral hospital in Brazil
Authors: Machado Claudia Regina , Brasil Deise , Dal Poz Mario Roberto 
Published: January 2022

Abstract
Background
The study analyzes the allocation of specialized doctors’ orthopedists in a high-complex hospital, using the WHO’s Workload Indicators of Staffing Need (WISN) methodology and approach, which measures the workload pressure on the healthcare team (positive, negative, or well-adjusted).

Methods
In the first phase, the hospital’s operations and activities were analyzed using the information system. The duration of the tasks performed by the specialist physicians was observed and directly measured in the second phase. Finally, the indicators were analyzed, and the workload was calculated using the WISN application. The measurement was made using the available work time per year divided by the time unit over the previous 12 months.

Results
The hand surgery care unit was WISN 1.0 and the ratios for the spine surgery care unit was 1.22, indicating enough physicians and no work overload among the groups surveyed. The ratio in the knee unit was 1.69, indicating that there was an excess of staffing for the workload.

Conclusion
The workload findings and staffing calculations were useful in supporting and orienting the design and implementation of measures to increase the efficiency and effectiveness of health services.
Applying the workload indicators of staffing needs method in nursing health workforce planning: evidences from four hospitals in Vietnam
Authors: Nguyen Thu Thi Hoai , Phung Hung Thanh , Bui Anh Thi My 
Published: January 2022

AbstractBackgroundVietnam has encountered difficulties in ensuring an adequate and equitable distribution of health workforce. The traditional staffing norms stated in the Circular 08/TT-BYT issued in 2007 based solely on population or institutional size and do not adequately take into consideration the variations of need such as population density, mortality and morbidity patterns. To address this problem, more rigorous approaches are needed to determine the number of personnel in health facilities. One such approach is Workload Indicators of Staffing Need (WISN) developed by the World Health Organization (WHO), a facility-based workforce planning method that assists managers in defining the responsibilities of different workforce categories and improving the appropriateness and efficiency of a staff mix.MethodsThis study applied the WISN approach and was employed in 22 clinical departments at four hospitals in Vietnam between 2015 and 2018. 22 targeted group discussions involving nurses were conducted. Hospital personnel records have been retrieved. The data were analyzed according to WISN instructions.ResultsOf the 22 departments, there was a shortage of 1 to 2 nurses in 10 departments, with WISN ratios ranging between 0.88 and 0.95. Only 01 clinical colleges at Can Tho Hospital lacked 05 nurses, facing a high workload with a WISN ratio of 0.78. Administrative time represented 20–40% of the total work time of a nurse. In comparison, nurses at Can Tho Hospital spent time on administration from 24 onwards. 5–41.7% of their working time while nurses at Thanh Hoa Hospital spent 21–33%.ConclusionsThe application of the WISN enabled health managers to analyze the workload of nurses, calculate staffing needs, and thus effectively contribute to the workforce planning process. It is expected that the results of this research will encourage the use of the WISN tool in other hospitals and health facilities across the health system. At provincial and national levels, this study provides important evidence to help policy makers develop guidelines for personnel norms for health facilities in the context of limited resources, while the existing regulation is no longer appropriate.
Assessment of staffing needs for registered nurses and licensed practical nurses at primary care units in Brazil using Workload Indicators of Staffing Need (WISN) method
Authors: Bonfim Daiana , Mafra Ana Carolina Cintra Nunes , da Costa Palacio Danielle , Rewa Talita 
Published: January 2022

Abstract
Background
The balance between supply and demand for primary health care (PHC) services is one of the main challenges to the health system in Brazil. In this context, the application of planning methods could benefit the decision-making process for human resources organizations. Hence, the objective of this study was to assess the staffing needs for registered nurses (RNs) and licensed practical nurses (LPNs) at PHC services using the WISN method.

Methods
The Workload Indicators of Staffing Need (WISN) methodology was applied at 13 Primary Care Units (PCU) located in the city of São Paulo, Brazil. It included 87 RNs and 174 LPNs, and used data from 2017 to 2019.

Results
The WISN results found that RNs were under high workload pressure at 10 PCUs (77%) in 2017 and 2018, with a decrease to 8 PCUs (61%) in 2019. For LPNs, high workload pressure increased from 2 PCUs (15%) in 2017 to 13 PCUs (100%) in 2018, with a decrease to 11 (85%) in 2019.

Conclusion
The assessment of staffing needs for RNs and LPNs at the PCUs included in the study identified a consistent deficit in the number of professionals, and high workload pressure in most services throughout the study period.
Circular RNAs and glioblastoma multiforme: focus on molecular mechanisms
Authors: Salami Raziyeh , Salami Marziyeh , Mafi Alireza , Vakili Omid , Asemi Zatollah 
Published: January 2022

AbstractGlioblastoma multiforme (GBM), as a deadly and almost incurable brain cancer, is the most invasive form of CNS tumors that affects both children and adult population. It accounts for approximately half of all primary brain tumors. Despite the remarkable advances in neurosurgery, radiotherapy, and chemotherapeutic approaches, cell heterogeneity and numerous genetic alterations in cell cycle control, cell growth, apoptosis, and cell invasion, result in an undesirable resistance to therapeutic strategies; thereby, the median survival duration for GBM patients is unfortunately still less than two years. Identifying new therapeutics and employing the combination therapies may be considered as wonderful strategies against the GBM. In this regard, circular RNAs (circRNAs), as tumor inhibiting and/or stimulating RNA molecules, can regulate the cancer-developing processes, including cell proliferation, cell apoptosis, invasion, and chemoresistance. Hereupon, these molecules have been introduced as potentially effective therapeutic targets to defeat GBM. The current study aims to investigate the fundamental molecular and cellular mechanisms in association with circRNAs involved in GBM pathogenesis. Among multiple mechanisms, the PI3K/Akt/mTOR, Wnt/β-catenin, and MAPK signaling, angiogenic processes, and metastatic pathways will be thoroughly discussed to provide a comprehensive understanding of the role of circRNAs in pathophysiology of GBM.
Moderate physical activity may not decrease the risk of cardiovascular disease in persistently overweight and obesity adults
Authors: Tian Qiuyue , Wang Biyan , Chen Shuohua , Wu Shouling , Wang Youxin 
Published: January 2022

Abstract
Background
Body mass index (BMI) and physical activity (PA) has been documented to be associated with cardiovascular disease (CVD). However, the evidences regarding joint phenotypes of BMI and PA trajectories with risk for CVD and all-cause mortality are still limited.

Methods
Participants from the Kailuan Study, followed up during 2006–2019 were included, with primary outcomes of CVDs (myocardial infarction or stroke) and all-cause mortality. BMI and PA were repeatedly measured at least three times, and thus joint phenotypes trajectory groups were identified by group-based trajectory modeling. Cox proportional hazards models were used to examine the associations between trajectory groups and CVDs and all-cause mortality.

Results
Totally 88,141 (6 trajectories) and 89,736 participants (5 trajectories) were included in the final analyses relating trajectories to CVDs and all-cause mortality, respectively. Compared with persistent normal-weight with moderate PA group, participants were associated with increased risk of CVD in persistent overweight with moderate PA trajectory group (adjusted hazard ratio [aHR]: 1.31, 95% confidence interval [CI]: 1.22–1.41) and persistent obesity with moderate PA trajectory group (aHR: 1.55, 95% CI: 1.41–1.69). While the rising to overweight with moderate PA in normal-weight status with active PA (aHR: 0.72, 95% CI: 0.65–0.79), persistent overweight with moderate PA (aHR: 0.92, 95% CI: 0.87–0.97) and decline to normal-weight in overweight status with moderate PA (aHR: 0.73, 95% CI: 0.67–0.80) trajectories group were significantly associated with decreased all-cause mortality risk. The associations remained robust among stratifying by age and sex individuals and sensitive analysis.

Conclusions
The long-term trajectories analysis showed that moderate PA may not decrease the risk of CVD in persistently overweight and obesity adults.
Real-time motion onset recognition for robot-assisted gait rehabilitation
Authors: Haji Hassani Roushanak , Bannwart Mathias , Bolliger Marc , Seel Thomas , Brunner Reinald , Rauter Georg 
Published: January 2022

AbstractBackgroundMany patients with neurological movement disorders fear to fall while performing postural transitions without assistance, which prevents them from participating in daily life. To overcome this limitation, multi-directional Body Weight Support (BWS) systems have been developed allowing them to perform training in a safe environment. In addition to overground walking, these innovative/novel systems can assist patients to train many more gait-related tasks needed for daily life under very realistic conditions. The necessary assistance during the users’ movements can be provided via task-dependent support designs. One remaining challenge is the manual switching between task-dependent supports. It is error-prone, cumbersome, distracts therapists and patients, and interrupts the training workflow. Hence, we propose a real-time motion onset recognition model that performs automatic support switching between standing-up and sitting-down transitions and other gait-related tasks (8 classes in total).MethodsTo predict the onsets of the gait-related tasks, three Inertial Measurement Units (IMUs) were attached to the sternum and middle of outer thighs of 19 controls without neurological movement disorders and two individuals with incomplete Spinal Cord Injury (iSCI). The data of IMUs obtained from different gait tasks was sent synchronously to a real-time data acquisition system through a custom-made Bluetooth-EtherCAT gateway. In the first step, data was applied offline for training five different classifiers. The best classifier was chosen based on F1-score results of a Leave-One-Participant-Out Cross-Validation (LOPOCV), which is an unbiased way of testing. In a final step, the chosen classifier was tested in real time with an additional control participant to demonstrate feasibility for real-time classification.ResultsTesting five different classifiers, the best performance was obtained in a single-layer neural network with 25 neurons. The F1-score of$$86.83\% \pm 6.2\%$$86.83%±6.2%and$$92.01\%$$92.01%are achieved on testing using LOPOCV and test data ($$30\%$$30%, participants = 20), respectively. Furthermore, the results from the implemented real-time classifier were compared with the offline classifier and revealed nearly identical performance (difference = $$0.08 \%$$0.08%).ConclusionsA neural network classifier was trained for identifying the onset of gait-related tasks in real time. Test data showed convincing performance for offline and real-time classification. This demonstrates the feasibility and potential for implementing real-time onset recognition in rehabilitation devices in future.
Human in silico trials for parametric computational fluid dynamics investigation of cerebrospinal fluid drug delivery: impact of injection location, injection protocol, and physiology
Authors: Khani Mohammadreza , Burla Goutham Kumar Reddy , Sass Lucas R. , Arters Ostin N. , Xing Tao , Wu Haiming , Martin Bryn A. 
Published: January 2022

Abstract
Background
Intrathecal drug delivery has a significant role in pain management and central nervous system (CNS) disease therapeutics. A fluid-physics based tool to assist clinicians in choosing specific drug doses to the spine or brain may help improve treatment schedules.

Methods
This study applied computational fluid dynamics (CFD) and in vitro model verification to assess intrathecal drug delivery in an anatomically idealized model of the human CSF system with key anatomic features of the CNS. Key parameters analyzed included the role of (a) injection location including lumbar puncture (LP), cisterna magna (CM) and intracerebroventricular (ICV), (b) LP injection rate, injection volume, and flush volume, (c) physiologic factors including cardiac-induced and deep respiration-induced CSF stroke volume increase. Simulations were conducted for 3-h post-injection and used to quantify spatial–temporal tracer concentration, regional area under the curve (AUC), time to maximum concentration (Tmax), and maximum concentration (Cmax), for each case.

Results
CM and ICV increased AUC to brain regions by ~ 2 logs compared to all other simulations. A 3X increase in bolus volume and addition of a 5 mL flush both increased intracranial AUC to the brain up to 2X compared to a baseline 5 mL LP injection. In contrast, a 5X increase in bolus rate (25 mL/min) did not improve tracer exposure to the brain. An increase in cardiac and respiratory CSF movement improved tracer spread to the brain, basal cistern, and cerebellum up to ~ 2 logs compared to the baseline LP injection.

Conclusion
The computational modeling approach provides ability to conduct in silico trials representative of CSF injection protocols. Taken together, the findings indicate a strong potential for delivery protocols to be optimized to reach a target region(s) of the spine and/or brain with a needed therapeutic dose. Parametric modification of bolus rate/volume and flush volume was found to have impact on tracer distribution; albeit to a smaller degree than injection location, with CM and ICV injections resulting in greater therapeutic dose to brain regions compared to LP. CSF stroke volume and frequency both played an important role and may potentially have a greater impact than the modest changes in LP injection protocols analyzed such as bolus rate, volume, and flush.