bluuebunny/crossref_metadata_2025 huggingface dataset:
Seroprevalence, spatial distribution, and social determinants of SARS-CoV-2 in three urban centers of Chile
Authors: Vial Pablo , González Claudia , Icaza Gloria , Ramirez-Santana Muriel , Quezada-Gaete Rubén , Núñez-Franz Loreto , Apablaza Mauricio , Vial Cecilia , Rubilar Paola , Correa Juan , Pérez Claudia , Florea Andrei , Guzmán Eugenio , Lavín María-Estela , Concha Paula , Nájera Manuel , Aguilera Ximena
Published: January 2022

Background

Seroprevalence studies provide an accurate measure of SARS-CoV-2 spread and the presence of asymptomatic cases. They also provide information on the uneven impact of the pandemic, pointing out vulnerable groups to prioritize which is particularly relevant in unequal societies. However, due to their high cost, they provide limited evidence of spatial spread of the pandemic specially in unequal societies. Our objective was to estimate the prevalence of SARS-CoV-2 antibodies in Chile and model its spatial risk distribution.

Methods

During Oct–Nov 2020, we conducted a population-based serosurvey in Santiago, Talca, and Coquimbo–La Serena (2493 individuals). We explored the individual association between positive results and socio-economic and health-related variables by logistic regression for complex surveys. Then, using an Empirical Bayesian Kriging model, we estimated the infection risk spatial distribution using individual and census information, and compared these results with official records.

Results

Seroprevalence was 10.4% (95% CI 7.8–13.7%), ranging from 2% (Talca) to 11% (Santiago), almost three times the number officially reported. Approximately 36% of these were asymptomatic, reaching 82% below 15 years old. Seroprevalence was associated with the city of residence, previous COVID-19 diagnosis, contact with confirmed cases (especially at household), and foreign nationality. The spatial model accurately interpolated the distribution of disease risk within the cities finding significant differences in the predicted probabilities of SARS-CoV-2 infection by census zone (IQR 2.5–15.0%), related to population density and education.

Conclusions

Our results underscore the transmission heterogeneity of SARS-CoV-2 within and across three urban centers of Chile. Socio-economic factors and the outcomes of this seroprevalence study enable us to identify priority areas for intervention. Our methodological approach and results can help guide the design of interdisciplinary strategies for urban contexts, not only for SARS-CoV-2 but also for other communicable diseases.
Clinical characteristics of healthcare workers with SARS-CoV-2 infection after vaccination with BNT162b2 vaccine
Authors: Lombardi Andrea , Renisi Giulia , Consonni Dario , Oggioni Massimo , Bono Patrizia , Uceda Renteria Sara , Piatti Alessandra , Pesatori Angela Cecilia , Castaldi Silvana , Muscatello Antonio , Riboldi Luciano , Ceriotti Ferruccio , Gori Andrea , Bandera Alessandra
Published: January 2022

Background

The pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had a significant impact worldwide. Vaccines against COVID-19 appear as a tool able to curb out mortality and reduce the circulation of the virus. Little is known so far about the clinical characteristics of individuals who developed SARS-CoV-2 infection after having received the vaccination, as well as the temporal relationship between vaccine administration and symptoms onset.

Methods

Retrospective cohort study among the 3219 healthcare workers (HCWs) of the Fondazione IRCCS Ospedale Maggiore Policlinico of Milano who received a full immunization with the BNT162b2 vaccine and who developed SARS-CoV-2 infection (documented through positive RT-PCR on nasopharyngeal swab) in March–April 2021.

Results

Overall, we have identified 15 HCWs with SARS-CoV-2 infection after vaccination, 7 (46.7%) of them were male and the mean age was 38.4 years (SD 14). In 4 of them, the presence of SARS-CoV-2 anti-nucleocapsid (anti-N) antibodies was assessed before vaccination and resulted positive in 1 case. In all HCWs the presence of SARS-CoV-2 anti-spike (anti-S1) antibodies was assessed, on average 42.2 days after the completion of vaccination, with a mean value of 2055 U/mL (SD 1927.3). SARS-CoV-2 infection was ascertained on average 56.2 days after vaccination. The mean cycle threshold (Ct) of SARS-CoV-2 PCR was 26.4, the lineage was characterized in 9 HCWs. None of the HCWs reported a primary or secondary immunodeficiency. Regarding symptoms, they were reported only by 7 (46.7%) HCWs and appeared on average 55 days after the second dose of vaccination. Of those who reported symptoms, one (14.3%) had fever, 7 (100%) rhinitis/conjunctivitis, 4 (57.1%) taste and smell alterations, none had respiratory symptoms, 4 headache/arthralgia (57.1%) and 1 gastrointestinal symptom (14.3%). All symptoms disappeared in a few days and no other unclassified symptoms were reported.

Conclusions

Infections occurring after vaccination with the BNT162b2 vaccine are mostly asymptomatic and are not associated with the serum titre of anti-S1 antibodies. We did not find a predominance of specific viral variants, with several lineages represented.
Identification of a ZC3H12D-regulated competing endogenous RNA network for prognosis of lung adenocarcinoma at single-cell level
Authors: Chen Wenhan , Guo Zhifeng , Wu Jingyang , Lin Guofu , Chen Shaohua , Lin Qinhui , Yang Jiansheng , Xu Yuan , Zeng Yiming
Published: January 2022

Background

To identify hub genes from the competing endogenous RNA (ceRNA) network of lung adenocarcinoma (LUAD) and to explore their potential functions on prognosis of patients from a single-cell perspective.

Methods

We performed RNA-sequencing of LUAD to construct ceRNA regulatory network, integrating with public databases to identify the vital pathways related to patients’ prognosis and to reveal the expression level of hub genes under different conditions, the functional enrichment of co-expressed genes and their potential immune-related mechanisms.

Results

ZC3H12D-hsa-miR-4443-ENST00000630242 axis was found to be related with LUAD. Lower ZC3H12D expression was significantly associated with shorter overall survival (OS) of patients (HR = 2.007, P < 0.05), and its expression was higher in early-stage patients, including T1 (P < 0.05) and N0 (P < 0.05). Additionally, ZC3H12D expression was higher in immune cells displayed by single-cell RNA-sequencing data, especially in Treg cells of lung cancer and CD8 T cells, B cells and CD4 T cells of LUAD. The functional enrichment analysis showed that the co-expressed genes mainly played a role in lymphocyte activation and cytokine-cytokine receptor interaction. In addition, ZC3H12D was associated with multiple immune cells and immune molecules, including immune checkpoints CTLA4, CD96 and TIGIT.

Conclusion

ZC3H12D-hsa-miR-4443-ENST00000630242 ceRNA network was identified in LUAD. ZC3H12D could affect prognosis of patients by regulating mRNA, miRNA, lncRNA, immune cells and immune molecules. Therefore, it may serve as a vital predictive marker and could be regarded as a potential therapeutic target for LUAD in the future.
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

Background

Child 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.

Methods

We 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.

Discussion

The 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 registration

www.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

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

N6-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

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

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

Background

Vietnam 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.

Methods

This 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.

Results

Of 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%.

Conclusions

The 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

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

Glioblastoma 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

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

Background

Many 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).

Methods

To 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.

Results

Testing 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%).

Conclusions

A 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

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.
Co-expression of cancer stem cell markers, SALL4/ALDH1A1, is associated with tumor aggressiveness and poor survival in patients with serous ovarian carcinoma
Authors: Sharbatoghli Mina , Shamshiripour Parisa , Fattahi Fahimeh , Kalantari Elham , Habibi Shams Zohre , Panahi Mahshid , Totonchi Mehdi , Asadi-Lari Zeynab , Madjd Zahra , Saeednejad Zanjani Leili
Published: January 2022

Background

Spalt-like transcription factor 4 (SALL4) and aldehyde dehydrogenase1 family member A1 (ALDH1A1) expressing cells have been characterized as possessing stem cell-like properties known as cancer stem cell marker in serous ovarian carcinoma (SOC).

Methods

The association between SALL4 and ALDH1A1 was observed based on literature review and bioinformatics tools. Therefore, this study aimed to investigate the association between the co-expression of SALL4/ALDH1A1 proteins and clinicopathological parameters and their prognostic value in SOC patients using immunohistochemical staining on tissue microarrays (TMAs). Furthermore, benign tumors and normal tissue samples were compared with the expression of the tumor tissue samples.

Results

Increased co-expression of SALL4/ALDH1A1 was found to be significantly associated with the advanced FIGO stage (P = 0.047), and distant metastasis (P = 0.028). The results of Kaplan–Meier survival analysis indicated significant differences between disease- specific survival (DSS; P = 0.034) or progression-free survival (PFS; P = 0.018) and the patients with high and low co-expression of SALL4/ALDH1A1, respectively. Furthermore, high level co-expression of SALL4/ALDH1A1 was a significant predictor of worse DSS and PFS in the univariate analysis. The data also indicated that the co-expression of SALL4/ALDH1A1 was an independent prognostic factor affecting PFS. Moreover, the co-expression of SALL4/ALDH1A1 added prognostic values of DSS in patients with SOC who had grade III versus grade I in multivariate analysis.

Conclusions

Our data demonstrated that high co-expression of SALL4/ALDH1A1 was found to be significantly associated with tumor aggressiveness and worse DSS or PFS in SOC patients. Therefore, co-expression of SALL4/ALDH1A1 may serve as a potential prognostic biomarker of cancer progression in these cases.
Activities supporting the growth of Clinical Trial Networks in Australia
Authors: Nemeh Fiona , Buchbinder Rachelle , Hawley Carmel M. , Nelson Mark R. , Waterkeyn Jacqui G. , Reid Christopher M.
Published: January 2022

Clinical Trial Networks in which trialists work collaboratively enable multi-site, large-scale, high-quality clinical trials to be efficiently run. Although the benefits of Clinical Trial Networks are largely known, establishing a Clinical Trial Network can be complex. There are many factors for clinicians and researchers to consider, and there is currently a paucity of information on how to form a Clinical Trial Network. This article provides a suggested roadmap on how to establish a Clinical Trial Network. The Australian Clinical Trials Alliance (ACTA) is the peak body for Clinical Trial Networks, Coordinating Centres and Registries in Australia, and has produced several resources to support the effective and efficient running of clinical trials. This guide has come about through discussions with members of the ACTA Clinical Trial Network Sector Expansion Reference Group consisting of clinical trialists, clinicians, researchers, and consumers.
Blood flow Restriction training After patellar INStability (BRAINS Trial)
Authors: Brightwell Benjamin D. , Stone Austin , Li Xiaojuan , Hardy Peter , Thompson Katherine , Noehren Brian , Jacobs Cale
Published: January 2022

Background

Patellar instability is a common and understudied condition that disproportionally affects athletes and military personnel. The rate of post-traumatic osteoarthritis that develops following a patellar dislocation can be up to 50% of individuals 5–15 years after injury. Conservative treatment is the standard of care for patellar instability however, there are no evidence-informed rehabilitation guidelines in the scientific literature. The purpose of this study is to assess the effectiveness of blood-flow restriction training (BFRT) for patellar instability. Our hypotheses are that this strategy will improve patient-reported outcomes and accelerate restoration of symmetric strength and knee biomechanics necessary to safely return to activity.

Methods/design

This is a parallel-group, superiority, randomized, double-blinded, placebo-controlled clinical trial at the University of Kentucky, sports medicine clinic that aims to recruit 78 patients with acute patellar dislocations randomly allocated into two groups: (1) sham BFRT and (2) BFRT. Both groups will receive the current standard of care physical therapy 3 times per week for up to 9 weeks. Physical therapy sessions will consist of typical standard of care treatment followed by BFRT or sham BFRT. Primary outcomes include the Norwich Patellar Instability Scale, quadriceps strength, and imaging and biochemical biomarkers of cartilage degradation.

Discussion

The current standard of care for non-operative treatment of patellar instability is highly variable does not adequately address the mechanisms necessary to restore lower extremity function and protect the long-term health of articular cartilage following injury. This proposed novel intervention strategy uses an easily implementable therapy to evaluate if BFRT significantly improves patient-reported outcomes, function, and joint health over the first year of recovery.

Trial registration

Blood Flow Restriction Training, Aspiration, and Intraarticular Normal Saline (BRAINS) NCT04554212. Registered on 18 September 2020.
The ALLEGRO trial: a placebo controlled randomised trial of intravenous lidocaine in accelerating gastrointestinal recovery after colorectal surgery
Authors: Paterson Hugh M. , Cotton Seonaidh , Norrie John , Nimmo Susan , Foo Irwin , Balfour Angie , Speake Doug , MacLennan Graeme , Stoddart Andrew , Innes Karen , Cameron Sarah , Aucott Lorna , McCormack Kirsty
Published: January 2022

Background

Return of gastrointestinal (GI) function is fundamental to patient recovery after colorectal surgery and is required before patients can be discharged from hospital safely. Up to 40% of patients suffer delayed return of GI function after colorectal surgery, causing nausea, vomiting and abdominal discomfort, resulting in longer hospital stay. Small, randomised studies have suggested perioperative intravenous (IV) lidocaine, which has analgesic and anti-inflammatory effects, may accelerate return of GI function after colorectal surgery. The ALLEGRO trial is a pragmatic effectiveness study to assess the benefit of perioperative IV lidocaine in improving return of GI function after elective minimally invasive (laparoscopic or robotic) colorectal surgery.

Methods

United Kingdom (UK) multi-centre double blind placebo-controlled randomised controlled trial in 562 patients undergoing elective minimally invasive colorectal resection. IV lidocaine or placebo will be infused for 6–12 h commencing at the start of surgery as an adjunct to usual analgesic/anaesthetic technique. The primary outcome will be return of GI function.

Discussion

A 6–12-h perioperative intravenous infusion of 2% lidocaine is a cheap addition to usual anaesthetic/analgesic practice in elective colorectal surgery with a low incidence of adverse side-effects. If successful in achieving quicker return of gut function for more patients, it would reduce the rate of postoperative ileus and reduce the duration of inpatient recovery, resulting in reduced pain and discomfort with faster recovery and discharge from hospital. Since colorectal surgery is a common procedure undertaken in every acute hospital in the UK, a reduced length of stay and reduced rate of postoperative ileus would accrue significant cost savings for the National Health Service (NHS).

Trial registration

EudraCT Number 2017-003835-12; REC Number 17/WS/0210 the trial was prospectively registered (ISRCTN Number:ISRCTN52352431); date of registration 13 June 2018; date of enrolment of first participant 14 August 2018.
Curcumin and zinc co-supplementation along with a loss-weight diet can improve lipid profiles in subjects with prediabetes: a multi-arm, parallel-group, randomized, double-blind placebo-controlled phase 2 clinical trial
Authors: Karandish Majid , Mozaffari-khosravi Hassan , Mohammadi Seyed Mohammad , Cheraghian Bahman , Azhdari Maryam
Published: January 2022

Background

Diabetes is one of the major public health concerns. Prediabetes can increase the risk of developing some non-communicable diseases such as type 2 diabetes. Given the increasing trend of prediabetes, it is critical to control it and prevent its complications. Curcumin is a major bioactive component of turmeric. Zinc is an antioxidant nutrient. The present trial aimed to evaluate the effect of curcumin and zinc co-supplementation along with a loss-weight diet on serum lipid profiles in overweight or obese patients with prediabetes.

Methods

Eighty-four participants were randomized to four groups (curcumin (500 mg/day), zinc (30 mg/day), “curcumin and zinc”, and placebo) for 90 days. Serum total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), non-HDL, HDL/LDL ratio, weight, BMI, waist circumstance (WC), hip circumstance (HC), physical activity (PA) and dietary intake were determined pre and post-intervention. This study will be conducted at Yazd Diabetes Research Clinic, Shahid Sadoughi University of Medical Sciences.

Results

Totally, 82 participants were included in the final analysis. After the adjusted PA effect, changes in serum TG (adjusted p = 0.001), LDL (adjusted p = 0.035), non-HDL (adjusted p = 0.003), HDL/LDL ratio (adjusted p = 0.002), and HDL (adjusted p < 0.0001) revealed a significant difference between the groups. However, the changes in weight (adjusted p = 0.004) and BMI (adjusted p = 0.006) were significant but the changes in dietary intake, PA, WC, and HC were non-significant (adjusted p ≥ 0.05). Despite that there was a significant difference for post-intervention HDL levels (adjusted p = 0.016), other lipid profiles showed no significant difference (adjusted p ≥ 0.05).

Conclusion

The beneficial effects of “curcumin and zinc” co-supplementation was reported for the changes of some lipid profiles (TG, LDL, HDL, non-HDL, and HDL to LDL ratio), BMI, and weight with no positive effects on TC, dietary intake, PA, WC, and HC. Therefore, it may play a potential role in the prevention of macro and microvascular complications.

Trial registration The project is a registered clinical trial (Registration number: IRCT20190902044671N1, Iranian Registry of Clinical Trials (IRCT), registered October 11, 2019.
Mendelian randomization highlights significant difference and genetic heterogeneity in clinically diagnosed Alzheimer’s disease GWAS and self-report proxy phenotype GWAX
Authors: Liu Haijie , Hu Yang , Zhang Yan , Zhang Haihua , Gao Shan , Wang Longcai , Wang Tao , Han Zhifa , Sun Bao-liang , Liu Guiyou
Published: January 2022

Background

Until now, Mendelian randomization (MR) studies have investigated the causal association of risk factors with Alzheimer’s disease (AD) using large-scale AD genome-wide association studies (GWAS), GWAS by proxy (GWAX), and meta-analyses of GWAS and GWAX (GWAS+GWAX) datasets. However, it currently remains unclear about the consistency of MR estimates across these GWAS, GWAX, and GWAS+GWAX datasets.

Methods

Here, we first selected 162 independent educational attainment genetic variants as the potential instrumental variables (N = 405,072). We then selected one AD GWAS dataset (N = 63,926), two AD GWAX datasets (N = 314,278 and 408,942), and three GWAS+GWAX datasets (N = 388,324, 455,258, and 472,868). Finally, we conducted a MR analysis to evaluate the impact of educational attainment on AD risk across these datasets. Meanwhile, we tested the genetic heterogeneity of educational attainment genetic variants across these datasets.

Results

In AD GWAS dataset, MR analysis showed that each SD increase in years of schooling (about 3.6 years) was significantly associated with 29% reduced AD risk (OR=0.71, 95% CI: 0.60–0.84, and P=1.02E−04). In AD GWAX dataset, MR analysis highlighted that each SD increase in years of schooling significantly increased 84% AD risk (OR=1.84, 95% CI: 1.59–2.13, and P=4.66E−16). Meanwhile, MR analysis suggested the ambiguous findings in AD GWAS+GWAX datasets. Heterogeneity test indicated evidence of genetic heterogeneity in AD GWAS and GWAX datasets.

Conclusions

We highlighted significant difference and genetic heterogeneity in clinically diagnosed AD GWAS and self-report proxy phenotype GWAX. Our MR findings are consistent with recent findings in AD genetic variants. Hence, the GWAX and GWAS+GWAX findings and MR findings from GWAX and GWAS+GWAX should be carefully interpreted and warrant further investigation using the AD GWAS dataset.
A new direction in managing avulsed teeth: stem cell-based de novo PDL regeneration
Authors: Aksel Hacer , Zhu Xiaofei , Gauthier Philippe , Zhang Wenjing , Azim Adham A. , Huang George T.-J.
Published: January 2022

Management of avulsed teeth after replantation often leads to an unfavorable outcome. Damage to the thin and vulnerable periodontal ligament is the key reason for failure. Cell- or stem cell-based regenerative medicine has emerged in the past two decades as a promising clinical treatment modality to improve treatment outcomes. This concept has also been tested for the management of avulsed teeth in animal models. This review focuses on the discussion of limitation of current management protocols for avulsed teeth, cell-based therapy for periodontal ligament (PDL) regeneration in small and large animals, the challenges of de novo regeneration of PDL on denuded root in the edentulous region using a mini-swine model, and establishing a prospective new clinical protocol to manage avulsed teeth based on the current progress of cell-based PDL regeneration studies.
Sex, age, and ethnic dependency of lipoprotein variants as the risk factors of ischemic heart disease: a detailed study on the different age-classes and genders in Tehran Cardiometabolic Genetic Study (TCGS)
Authors: Lanjanian Hossein , Najd Hassan Bonab Leila , Akbarzadeh Mahdi , Moazzam-Jazi Maryam , Zahedi Asiyeh Sadat , Masjoudi Sajedeh , Daneshpour Maryam S.
Published: January 2022

Biological processes involving environmental and genetic factors drive the interplay between age- and sex-regulating lipid profile. The relation between variations in the LPA gene with increasing the risk of coronary heart disease is dependent on population differences, sex, and age. The present study tried to do a gene candidate association analysis in people with myocardial infarction (MI) in a 22 year cohort family-based longitudinal cohort study, Tehran Cardiometabolic Genetic Study (TCGS). After adjusting p value by the FDR method, only the association of rs6415084 with the MI probability and the age-of-CHD-onset was significant in males in their middle age (p < 0.005). Surprisingly, a lack of association was observed for the rest of the markers (16 SNPs). These results revealed the moderator effects of age and sex on the association between the genetic variants (SNPs) of LPA and heart disease risk. Our observations may provide new insights into the biology that underlies lipid profile with age or the sexual dimorphism of Lp(a) metabolism. Finally, Lp(a) appears to be an independent risk factor; however, the role of sex and ethnicity is important.
Exploring pastoralists’ perceptions of desertification tipping points in Namibia’s communal drylands: An ethnographic case study from Okakarara constituency
Authors: Menestrey Schwieger Diego Augusto
Published: January 2022

Most studies and conceptualizations of tipping points in environmental and climatic systems have been conducted using natural science perspectives and approaches. Socio-scientific contributions—including Anthropology—are scarce. This has resulted in a limited understanding of the socio-cultural dimensions of tipping point phenomena at the local level. This paper contributes to ongoing discussion and provides an ethnographic study of local perceptions of desertification tipping points (DTPs) amongst Ovaherero pastoralists in Namibia’s semi-arid Okakarara constituency. Following a qualitative approach, this study shows that experienced farmers are aware of these phenomena and have accumulated extensive knowledge enabling them to identify and anticipate DTPs in different, complementary ways. The paper discusses how DTPs are managed in a communally farmed setting and presents the challenges that livestock farmers face in practical prevention of DTPs.