bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of analgesic ear drops as add-on treatment to oral analgesics in children with acute otitis media: study protocol of the OPTIMA pragmatic randomised controlled trial
Authors: de Sévaux Joline L H , Damoiseaux Roger A M J , Hullegie Saskia , Sanders Elisabeth A M , de Wit G Ardine , Zuithoff Nicolaas P A , Yardley Lucy , Anthierens Sibyl , Little Paul , Hay Alastair D , Schilder Anne G M , Venekamp Roderick P 
Published: February 2023

IntroductionEar pain is the most prominent symptom of childhood acute otitis media (AOM). To control the pain and reduce reliance on antibiotics, evidence of effectiveness for alternative interventions is urgently needed. This trial aims to investigate whether analgesic ear drops added to usual care provide superior ear pain relief over usual care alone in children presenting to primary care with AOM.Methods and analysisThis is a pragmatic, two-arm, individually randomised, open, superiority trial with cost-effectiveness analysis and nested mixed-methods process evaluation in general practices in the Netherlands. We aim to recruit 300 children aged 1–6 years with a general practitioner (GP) diagnosis of AOM and ear pain. Children will be randomly allocated (ratio 1:1) to either (1) lidocaine hydrochloride 5 mg/g ear drops (Otalgan) one to two drops up to six times daily for a maximum of 7 days in addition to usual care (oral analgesics, with/without antibiotics); or (2) usual care. Parents will complete a symptom diary for 4 weeks as well as generic and disease-specific quality of life questionnaires at baseline and 4 weeks. The primary outcome is the parent-reported ear pain score (0–10) over the first 3 days. Secondary outcomes include proportion of children consuming antibiotics, oral analgesic use and overall symptom burden in the first 7 days; number of days with ear pain, number of GP reconsultations and subsequent antibiotic prescribing, adverse events, complications of AOM and cost-effectiveness during 4-week follow-up; generic and disease-specific quality of life at 4 weeks; parents’ and GPs’ views and experiences with treatment acceptability, usability and satisfaction.Ethics and disseminationThe Medical Research Ethics Committee Utrecht, the Netherlands, has approved the protocol (21-447/G-D). All parents/guardians of participants will provide written informed consent. Study results will be submitted for publication in peer-reviewed medical journals and presented at relevant (inter)national scientific meetings.Trial registrationThe Netherlands Trial Register: NL9500; date of registration: 28 May 2021. At the time of publication of the study protocol paper, we were unable to make any amendments to the trial registration record in the Netherlands Trial Register. The addition of a data sharing plan was required to adhere to the International Committee of Medical Journal Editors guidelines. The trial was therefore reregistered in ClinicalTrials.gov (NCT05651633; date of registration: 15 December 2022). This second registration is for modification purposes only and the Netherlands Trial Register record (NL9500) should be regarded as the primary trial registration.
Pregnancy, obstetrical and neonatal outcomes in women exposed to physician-related occupational hazards: a scoping review
Authors: Marsters Candace M , Stafl Lenka , Bugden Sarah , Gustainis Rita , Nkunu Victoria , Reimer Renee , Fletcher Sarah , Smith Stephanie , Bruton Joe Moss , Hyde Christine , Dance Erica , Ruzycki Shannon M 
Published: February 2023

ObjectiveEvidence is needed to guide organisational decision making about workplace accommodations for pregnant physicians. Our objective was to characterise the strengths and limitations of current research examining the association between physician-related occupational hazards with pregnancy, obstetrical and neonatal outcomes.DesignScoping review.Data sourcesMEDLINE/PubMed, EMBASE, CINAHL/ EBSCO, SciVerse Scopus and Web of Science/Knowledge were searched from inception to 2 April 2020. A grey literature search was performed on 5 April 2020. The references of all included articles were hand searched for additional citations.Eligibility criteriaEnglish language citations that studied employed pregnant people and any ‘physician-related occupational hazards’, meaning any relevant physical, infectious, chemical or psychological hazard, were included. Outcomes included any pregnancy, obstetrical or neonatal complication.Data extraction and synthesisPhysician-related occupational hazards included physician work, healthcare work, long work hours, ‘demanding’ work, disordered sleep, night shifts and exposure to radiation, chemotherapy, anaesthetic gases or infectious disease. Data were extracted independently in duplicate and reconciled through discussion.ResultsOf the 316 included citations, 189 were original research studies. Most were retrospective, observational and included women in any occupation rather than healthcare workers. Methods for exposure and outcome ascertainment varied across studies and most studies had a high risk of bias in data ascertainment. Most exposures and outcomes were defined categorically and results from different studies could not be combined in a meta-analysis due to heterogeneity in how these categories were defined. Overall, some data suggested that healthcare workers may have an increased risk of miscarriage compared with other employed women. Long work hours may be associated with miscarriage and preterm birth.ConclusionsThere are important limitations in the current evidence examining physician-related occupational hazards and adverse pregnancy, obstetrical and neonatal outcomes. It is not clear how the medical workplace should be accommodated to improve outcomes for pregnant physicians. High-quality studies are needed and likely feasible.
Study protocol for a phase 1, randomised, double-blind, placebo-controlled study to investigate the safety, tolerability and pharmacokinetics of ascending topical doses of TCP-25 applied to epidermal suction blister wounds in healthy male and female volunteers
Authors: Lundgren Sigrid , Wallblom Karl , Fisher Jane , Erdmann Susanne , Schmidtchen Artur , Saleh Karim 
Published: February 2023

IntroductionTCP-25 gel is intended for use in treatment of wound infection and inflammation. Current local therapies for wounds have limited efficacy to prevent infections and there are no wound treatments available today that target the excessive inflammation that often hampers wound healing in both acute and chronic wounds. There is therefore a high medical need for new therapeutic alternatives.Methods and analysisA randomised, double-blinded, first-in-human study was designed to evaluate the safety, tolerability and potential systemic exposure of three increasing doses of the TCP-25 gel applied topically on suction blister wounds in healthy adults. The dose-escalation will be divided into three sequential dose groups with eight subjects in each group (24 patients in total). Within each dose group, the subjects will receive four wounds, with two wounds on each thigh. Each subject will receive TCP-25 on one wound per thigh and placebo on one wound per thigh in a randomised double-blinded manner, with a reverse reciprocal position on each respective thigh, to a total of five doses over 8 days. An internal safety review committee will monitor emerging safety and plasma concentration data over the course of the study and must give a favourable recommendation prior to initiating the next dose group, which will receive placebo gel or a higher concentration of TCP-25 in exactly the same manner described above.Ethics and disseminationThe study will be performed in accordance with ethical principles consistent with the Declaration of Helsinki, ICH/GCPE6 (R2), European Union Clinical Trials Directive and applicable local regulatory requirements.This study is approved by the Swedish Medical Products Agency and the Swedish ethics committee under the registration number 2022-00527-01. The results of this study will be disseminated via publication to a peer-reviewed journal at the discretion of the Sponsor.Trial registration numberNCT05378997.
Associations between lean maturity in primary care and musculoskeletal complaints among staff: a longitudinal study
Authors: Kaltenbrunner Monica , Mathiassen Svend Erik , Bengtsson Lars , Högberg Hans , Engström Maria 
Published: February 2023

ObjectiveThis study had two aims: (1) to determine the prevalence of musculoskeletal complaints among staff in primary care and (2) to determine to what extent lean maturity of the primary care unit can predict musculoskeletal complaints 1 year later.DesignDescriptive, correlational and longitudinal design.SettingPrimary care units in mid-Sweden.ParticipantsIn 2015, staff members responded to a web survey addressing lean maturity and musculoskeletal complaints. The survey was completed by 481 staff members (response rate 46%) at 48 units; 260 staff members at 46 units also completed the survey in 2016.Outcome measuresAssociations with musculoskeletal complaints were determined both for lean maturity in total and for four Lean domains entered separately in a multivariate model, that is, philosophy, processes, people and partners, and problem solving.ResultsThe shoulders (12-month prevalence: 58%), neck (54%) and low back (50%) were the most common sites of 12-month retrospective musculoskeletal complaints at baseline. Shoulders, neck and low back also showed the most complaints for the preceding 7 days (37%, 33% and 25%, respectively). The prevalence of complaints was similar at the 1-year follow-up. Total lean maturity in 2015 was not associated with musculoskeletal complaints, neither cross-sectionally nor 1 year later, for shoulders (1 year β: −0.002, 95% CI −0.03 to 0.02), neck (β: 0.006, 95% CI −0.01 to 0.03), low back (β: 0.004, 95% CI −0.02 to 0.03) and upper back (β: 0.002, 95% CI −0.02 to 0.02).ConclusionThe prevalence of musculoskeletal complaints among primary care staff was high and did not change within a year. The extent of lean maturity at the care unit was not associated with complaints among staff, neither in cross-sectional analyses nor in a 1-year predictive analysis.
Bone health in Norwegian female elite runners: a cross-sectional, controlled study
Authors: Kyte Karoline Holsen , Haakstad Lene A H , Hisdal Jonny , Sunde Andrine , Stensrud Trine 
Published: February 2023

ObjectiveThe primary objective was to compare bone mineral density (BMD) in Norwegian female elite long-distance runners with a control group of inactive females. Secondary objectives were to identify cases of low BMD, to compare the concentration of bone turnover markers, vitamin D and symptoms of low energy availability (LEA) between the groups, and to identify possible associations between BMD and selected variables.MethodsFifteen runners and fifteen controls were included. Assessments included dual-energy X-ray absorptiometry measurement of BMD in the total body, lumbar spine and dual proximal femur. Blood samples included endocrine analyses and circulating bone turnover markers. The risk of LEA was assessed through a questionnaire.ResultsRunners had higher Z-scores in the dual proximal femur (1.30 (0.20 to 1.80) vs 0.20 (−0.20 to 0.80), p<0.021) and total body (1.70 (1.20 to 2.30) vs 0.90 (0.80 to 1.00), p<0.001). The lumbar spine Z-score was similar between groups (0.10 (−0.70 to 0.60) vs −0.10(−0.50 to 0.50), p=0.983). Three runners had low BMD (Z-score <−1) in the lumbar spine. Vitamin D and bone turnover markers showed no differences between the groups. Forty-seven per cent of the runners were at risk of LEA. Dual proximal femur BMD showed a positive correlation to estradiol and a negative correlation to LEA symptoms in runners.ConclusionNorwegian female elite runners had higher BMD Z-score in the dual proximal femur and total body compared with controls, while no difference was observed in the lumbar spine. The advantages of long-distance running on bone health seem to be site specific, and there is still a need for the prevention of LEA and menstrual disorders in this group.
Nutrition risk varies according to social network type: data from the Canadian Longitudinal Study on Aging
Authors: Mills Christine Marie , Keller Heather H , DePaul Vincent Gerard , Donnelly Catherine 
Published: February 2023

ObjectiveThere were two primary objectives, namely: (1) to determine the social network types that Canadian adults aged 45 and older belong to and (2) to discover if social network type is associated with nutrition risk scores and the prevalence of high nutrition risk.DesignA retrospective cross-sectional study.SettingData from the Canadian Longitudinal Study on Aging (CLSA).Participants17 051 Canadians aged 45 years and older with data from baseline and first follow-up of the CLSA.ResultsCLSA participants could be classified into one of seven different social network types that varied from restricted to diverse. We found a statistically significant association between social network type and nutrition risk scores and percentage of individuals at high nutrition risk at both time points. Individuals with restricted social networks had lower nutrition risk scores and are more likely to be at nutrition risk, whereas individuals with diverse social networks had higher nutrition risk scores and are less likely to be at nutrition risk.ConclusionsSocial network type was associated with nutrition risk in this representative sample of Canadian middle-aged and older adults. Providing adults with opportunities to deepen and diversify their social networks may decrease the prevalence of nutrition risk. Individuals with more restricted networks should be proactively screened for nutrition risk.
Endovascular treatment versus medical management for mild stroke with acute anterior circulation large vessel occlusion: a meta-analysis
Authors: Qin Bin , Zhang Yunli , Liang Shuolin , Liang Huo , Tang Shiting , Liang Zhijian 
Published: February 2023

BackgroundThe effectiveness of endovascular treatment (EVT) in patients with mild stroke (National Institutes of Health Stroke Scale score ≤5) and acute anterior circulation large vessel occlusion (AACLVO) remains unknown.ObjectiveTo conduct a meta-analysis to compare the efficacy and safety of EVT in patients with mild stroke and AACLVO.MethodsEMBASE, Cochrane Library, PubMed, and Clinicaltrials.gov databases were searched until October 2022. Both retrospective and prospective studies which compared the clinical outcomes between EVT and medical treatment were included. ORs and 95% confidence intervals (CIs) for excellent and favorable functional outcomes, symptomatic intracranial hemorrhage (ICH), and mortality were pooled using a random-effects model. A propensity score (PS)-based methods adjusted analysis was also performed.Results4335 patients from 14 studies were included. In patients with mild stroke and AACLVO, EVT presented no marked differences in excellent and favorable functional outcomes and mortality compared with medical treatment. A higher risk of symptomatic ICH (OR=2.79; 95% CI 1.49 to 5.24; P=0.001) was observed with EVT. Subgroup analysis revealed that EVT had potential benefit for proximal occlusions with excellent functional outcomes (OR=1.68; 95% CI 1.01 to 2.82; P=0.05). Similar results were observed when PS-based methods adjusted analysis was used.ConclusionEVT did not significantly benefit clinical functional outcomes in comparison with medical treatment in patients with mild stroke and AACLVO. However, it may improve functional outcomes when treating patients with proximal occlusion, despite being associated with an increased risk of symptomatic ICH. Stronger evidence from ongoing randomized controlled trials is required.
Delving into the death signaling pathway of hemp oil and gamma radiation in solid tumor bearing mice
Authors: Hassan A.A. , Mansour S.Z. , Mostafa D.M. , Abdelgayed S.S. 
Published: February 2023

Many studies reported the diverse therapeutic potential of essential oils. They have a crucial role in cancer prevention and treatment. Antioxidant, antimutagenic, and antiproliferative are mechanisms involved. Also, essential oils may enhance immune function and surveillance, induce enzymes, enhance detoxification, and modulate multidrug resistance. Hemp oil, obtained from Cannabis sativaL. seeds, is known for its health-enhancing properties and bioactivity. Adult female Swiss albino mice were injected with viable Ehrlich ascites carcinoma cells (2.5 × 106 cells/mouse), and then administered with hemp oil (20 mg/kg) daily for 10 consecutive days pre-, and then 10 days post-exposure to 6 Gy whole-body gamma irradiation. Hemp oil significantly increased Beclin1, VMP1, LC3, cytochrome c, and Bax. More interestingly, Hemp oil showed a significant decrease in Bcl2 and P13k either alone or in combination with γ radiation. Finally, this study documented the possible role of hemp oil in inducing two cell death types, autophagy and apoptosis, as it may be applied as an adjuvant in cancer treatment.
Abundant explicit and exact solutions for the space–time fractional Vakhnenko–Parkes model in the relaxing medium with stability analysis
Authors: Tripathy A. , Sahoo S. 
Published: February 2023

In this work, we have considered the beta-fractional derivative form of the Vakhnenko–Parkes equation (VPE) to study its novel analytical solutions. To achieve the required new distinct traveling wave solutions, the new sub-equation method is used for the space–time fractional VPE. The dynamics of these solutions are analyzed under different parametric and fractional conditions by the graphical view. The produced wave patterns include combined bright–dark, w-shape, u-shape, v-shape, bright, propagation of two solitons, combined dark–bright, bell shape, a dark, periodic wave, breather, v-shape with two bright spots and combined anti-peakon–bright solutions. In recognizing the physical significance of the obtained wave solutions at each fraction of an interval, these solutions are highly commendable. In addition, to show the stability of the considered model, the stability analysis of the governing model is discussed by the linear stability analysis method which states the behavior of the model in the corresponding medium. These solutions are useful to study the proliferation of high-frequency waves in the relaxing medium.
What Ever Happened to Peer-to-Peer Systems?
Authors: Baquero Carlos 
Published: February 2023

The
Communications
website, https://cacm.acm.org, features more than a dozen bloggers in the BLOG@CACM community. In each issue of
Communications
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https://cacm.acm.org/blogs/blog-cacm
Carlos Baquero ponders the peer-to-peer paradigm.
Nutrient Density and Microbial Safety of Open-Air-Dried Beef Meat and Its Biochemical and Organ Histopathology Effects in Albino Rats: A Promising Ingredient for Complementary Food Formulation
Authors: Habte Kifle , Azene Meseret , Chanyalew Yohannes , Girma Samson , Bashea Chala , Yehualshet Asrat , Behailu Getamesay , Abebe Abiy , Tessema Masresha 
Published: February 2023

Introduction. Dried beef meat is a major source of essential fatty acids, minerals, and vitamins that are digestible and absorbable, thus could be a potential source of nutrients in complementary food formulations. Composition, microbial safety, and organ function tests were analyzed, and histopathological effect of air-dried beef meat powder was determined in rat model. Methods. Three groups of diets were given for the three groups of animals: (1) standard rat diet, (2) meat powder+standard rat diet (1 : 1 formulation), and (3) dried meat powder. A total of 36 Wistar albino rats (18 males and 18 females) of 4-8 weeks old were used and randomly assigned to the experiments. After acclimatization for one week, the experimental rats were followed for 30 days. Microbial analysis, nutrient composition, organ histopathology (liver and kidney), and organ function tests were conducted from serum samples taken from the animals. Results. Protein, fat, fiber, ash, utilizable carbohydrate, and energy contents of meat powder on a dry weight basis were

76.12
±
3.68

,

8.19
±
2.01

,

0.56
±
0.38

,

6.45
±
1.21

,

2.79
±
0.38

g
/
100

g

, and

389.30
±
3.25

kcal
/
100

g

, respectively. Meat powder could be also a potential source of minerals such as potassium (

766.16
±
77.26

mg
/
100

g

), phosphorus (

150.35
±
16.26

mg
/
100

g

), calcium (

18.15
±
7.80

mg
/
100

g

), zinc (

3.82
±
0.10

mg
/
100

g

), and sodium (

123.76
±
32.71

mg
/
100

g

). Food intakes were lower in MP group compared to the others. According to organ histopathology results, animals fed with the diet have shown normal values, except rise in alkaline phosphatase (ALP) and creatine kinase (CK) in groups fed with meat powder. The results of organ function tests were all within the acceptable ranges and comparable with their counterpart control groups. However, some of the microbial contents of the meat powder were not within the recommended level. Conclusion. Dried meat powder has a higher amount of nutrients, which would be a potential recipe in complementary food preparation that can support to reduce child malnutrition. However, further studies need to be conducted on the sensory acceptability of formulated complementary foods containing dried meat powder; also, clinical trials are aimed at observing the effect of dried meat powder on child linear growth.
Netrin-1 Promotes the Immunosuppressive Activity of MDSCs in Colorectal Cancer
Authors: Xia Xueli , Mao Zhenwei , Wang Wenxin , Ma Jie , Tian Jie , Wang Shengjun , Yin Kai 
Published: February 2023

Abstract
Myeloid-derived suppressive cells (MDSC) inhibit antitumor immunity and confer a survival advantage for tumor evasion. Tumor cells also support MDSC expansion and recruitment by secreting multiple growth factors and cytokines, but the mechanisms by which tumors affect MDSC function are not completely understood. Here, we found that the neuronal guidance protein netrin-1 was selectively secreted by MC38 murine colon cancer cells, which could enhance the immunosuppressive activity of MDSCs. MDSCs predominantly expressed one type of netrin-1 receptor, adenosine receptor 2B (A2BR). Netrin-1 interacted with A2BR on MDSCs to activate the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway, which ultimately increased CREB phosphorylation in MDSCs. Furthermore, netrin-1 knockdown in tumor cells inhibited the immunosuppressive activity of MDSCs and restored antitumor immunity in MC38 tumor xenograft mice. Intriguingly, high netrin-1 in the plasma correlated with MDSCs in patients with colorectal cancer. In conclusion, netrin-1 significantly enhanced the immunosuppressive function of MDSCs through A2BR on MDSCs, thus promoting the development of tumors. These findings highlight that netrin-1 may regulate the abnormal immune response in colorectal cancer and may become a potential target for immunotherapy.