bluuebunny/crossref_metadata_2025 huggingface dataset:
A mixed-methods process evaluation of the feasibility and acceptability of involving community and peer role models within a physical activity intervention for primary-school-aged girls (the CHARMING study)
Authors: Morgan Kelly , Van Godwin Jordan , Cannings-John Rebecca , Hallingberg Britt , Moore Graham , Pell Bethan , Whiteley Holly , Hawkins Jemma
Published: October 2023

Background

Role models have been identified as a potential means to tackle the persisting low levels of physical activity among young girls. The aim of this research was to explore the involvement of community- and peer role models within the CHARMING (CHoosing Active Role Models to INspire Girls) intervention, an intervention which aims to increase and sustain physical activity among 9–10-year-old girls. The research questions were, is it feasible and acceptable to recruit role models? and what are the perceived barriers and facilitators to the inclusion of peer role models within the intervention?

Methods

A mixed methods process evaluation was embedded within a larger feasibility study, involving three secondary schools and four adjoining primary schools in South Wales, United Kingdom. One-to-one interviews were conducted with teachers (N = 10) across the seven schools and community role models (N = 10). Focus groups were conducted with 18 peer role models (older girls from adjoining secondary schools) and 18 girls aged 9–10-years who had participated in the intervention. Primary school teachers kept observation logs of each intervention session. A researcher completed observation logs of two random sessions per school. Qualitative data were analysed using thematic analysis with a combined deductive and inductive coding approach. Observation data were analysed using descriptive statistics. Data were triangulated and comparative analyses conducted across schools.

Results

Twenty-three peer role models (aged 12–16-years) and 16 community role models participated in intervention delivery. Overall, the inclusion of both types of role models was shown as acceptable and feasible within the CHARMING intervention. Observation data highlighted key areas (i.e., intervention components delivered inconsistently) for further qualitative exploration. Six themes were identified during analyses; reach and access, communication, logistics, existing systems, interpersonal relationships, and perceived impacts. Themes were intertwined across the barriers and facilitators of recruitment and implementation. Areas for future improvement were highlighted.

Conclusions

Findings can be used to optimise the CHARMING intervention and inform wider interventions or policies employing several role models across settings to promote physical activity among children.
Nutrition facts labels: who is actually reading them and does it help in meeting intake recommendations for nutrients of public health concern?
Authors: Storz Maximilian Andreas
Published: October 2023

Background

Fiber, potassium and calcium are nutrients of public health concern and their intakes in the United States are alarmingly low. The usage of nutrition facts labels has been reported to increase the odds for dietary reference intake of fiber in some studies. The overall evidence, however, is mixed, as some studies suggested that nutrition facts panels have little to no effect on average measures of diet quality. Here, we investigated whether the usage of nutrition facts labels was associated with meeting U.S. intake recommendations for three nutrients of public health concern: fiber, potassium and calcium.

Methods

We used cross-sectional multistage, stratified, clustered and probability sampling design data from the U.S. National Health and Nutrition Examination Surveys 2017–2020 cycle. The sample included 5,416 individuals aged 20 years or older, which may be extrapolated to represent 146,841,866 US Americans. Nutrient intakes were compared among individuals reading nutrition facts panels “frequently”, “sometimes” or “rarely” using applied survey data analyses techniques (including multivariate logistic regression and marginsplots).

Results

We observed substantial sociodemographic differences between the three groups. Frequent readers were significantly more likely to be female and had higher educational levels. On average, they were also significantly older as compared to rare readers. Fiber intake in g/d was highest in frequent readers (17.09) and lowest in rare readers (14.64). The proportion of participants that met dietary fiber intake recommendations was almost four times higher in the frequent readers group (12.69%) as compared to the rare readers group (3.69%). In a bivariate logistic regression model, frequent label reading significantly increased the odds for meeting the fiber recommendations in Dietary Guidelines for Americans (OR: 2.15, p < 0.001). Rarely reading labels decreased the odds (OR: 0.57, p = 0.003). These odds remained essentially unchanged after adjusting for sociodemographic covariates, diabetes status and body mass index (OR: 1.84, p = 0.004; and OR: 0.62, p = 0.022).

Conclusions

Nutrition facts panel reading associates with fiber intake. Our findings have potential implications for public health nutrition strategies that may center around educational work.
Managing persistent physical symptoms when being social and active is the norm: a qualitative study among young people in Denmark
Authors: Andersen Julie Høgsgaard , Risør Mette Bech , Frostholm Lisbeth , Rask Mette Trøllund , Rosendal Marianne , Rask Charlotte Ulrikka
Published: October 2023

Background

An increasing number of young people in Western countries report persistent physical symptoms (PPS). PPS may disturb everyday activities and they may have negative consequences for later adult mental and physical health. Still little is known about how young people handle PPS in their everyday lives. This study examines how young people with PPS attempt to manage their symptoms while staying engaged in their daily activities and what is at stake in these attempts.

Methods

This qualitative study involved semi-structured interviews with 11 young people with PPS. Photo-elicitation was used to capture the participants’ experiences as they occurred in their everyday lives. The data material was analysed using a thematic analysis approach, as well as theory on subjectivity and social acceleration.

Results

The participants employed alleviating measures and tried to find patterns between their activities and the severity of their symptoms in order to adjust their activity level. Decisions not to participate in social activities were accompanied by feelings of missing out. The participants’ attempts at adjusting their activity level was challenged by norms of being social and active, and they experienced difficulty prioritizing their activities and explaining their symptoms to others.

Conclusion

PPS shaped the participants’ sense of how to act towards their bodies and social relationships in interaction with societal norms. The participants’ subject formation and symptom experiences should thus be seen as a biosocial process.
Oral health status and hygiene practices among visually impaired adolescents from a school in Kenya
Authors: Macharia Maureen , Masiga Mary , Psiwa Nathan , Bermudez Janella , Seminario Ana Lucia , Kemoli Arthur Musakulu
Published: October 2023

Background

Visual impairment affects a significant population globally. The aim of this study was to determine the oral health status and oral hygiene practices among visually impaired adolescents from a school in Kenya.

Methods

A descriptive cross-sectional study was carried out among 159 adolescents aged 10–19 years attending the largest public primary boarding school for the blind in Kenya. A questionnaire was used to record participants’ socio-demographic variables and oral hygiene practices. Clinical examination was undertaken to assess oral health status which consisted of oral hygiene, gingival health, and dental caries. Bivariate analyses were conducted to compare dental health outcomes across socio-demographic characteristics.

Results

There were 69 (43.4%) and 90 (56.6%) participants in Category I and II visual impairment respectively, 85 (53.5%) were male and 74 (46.5%) were female. Study participants were divided into three age categories: 10–12 years 48 (30.2%), 13–15 years 67 (42.1%), and 16- 19 years 44 (27.7%), with an overall mean age of 13.9 ± 2.3. All participants brushed their teeth, majority 107 (67.3%) brushed two or more times daily. Only 66 (41.5%) of the participants replaced their toothbrushes at 3 months. Sex (p =< 0.001) and age (p = 0.04) influenced frequency of toothbrush replacement. The average plaque score and gingival score index was 0.95 ± 0.45 and 0.28 ± 0.25 respectively, with gingivitis prevalence of 88.1%. Overall dental caries prevalence was 44.7%, [42.1%)] permanent dentition and [8.2%] deciduous dentition. Mean DMFT and dmft were 0.44 ± 0.60 and 0.12 ± 0.32 respectively. DMFT had a statistically significant association with sex (t = 1.82, p = 0.03). Oral hygiene practices did not influence oral hygiene and dental caries status. However, a statistically significant association was reported between frequency of toothbrush replacement and gingival score index (“p” =< 0.001).

Conclusions

The study reported general good oral hygiene, prevalent gingivitis 140 (88.1%), and almost half of the study population affected by dental caries 71 (44.7%). Most participants were unaware of using fluoridated toothpaste and of needing to change toothbrushes within 3 months. Frequency of toothbrush replacement was reported to influence gingival score index.
Evaluation of the proximal contact tightness in class II resin composite restorations using different contact forming instruments: a 1-year randomized controlled clinical trial
Authors: Abbassy Karim M. , Elmahy Waleed A. , Holiel Ahmed A.
Published: October 2023

Background

Proper proximal contact in direct composite restorations is crucial for periodontal health. Over a one-year period, this study was conducted to assess successive biological changes in proximal contact tightness PCT in class II direct composite restorations and the adjacent teeth by applying sectional matrix system along with different contact forming instruments.

Methods

72 direct compound class II composite restorations were performed in patients aged 18–40 years and divided into 4 groups: Group I (n = 18): proximal contact was restored with Palodent plus sectional matrix system, Group II (n = 18): Trimax as contact forming instrument, Group III (n = 18): Perform as contact forming instrument and Group IV (n = 18): Contact pro as contact forming instrument. All contact forming instruments were used along with Palodent plus matrix system. PCT was measured using a digital force gauge before (T0), immediate post operative (T1) and at 3 (T2), 6 (T3), 9 (T4), and 12 months (T5) after restorative treatment. Using One-Way ANOVA, Tukey’s post hoc test, and Bonferroni correction, PCT values were compared between groups before and after the intervention restoration. Meanwhile, for comparisons within groups, a paired t-test was conducted (p ≤ 0.05).

Results

Contact forming instruments combined with Palodent plus sectional matrix system achieved better PCT. Trimax led to a statistically considerable tighter proximal contacts than the other groups (p < 0.05). No statistically significant difference was found in PCT between Contact pro-2, Perform and Palodent plus sectional matrix system. By means of multivariate analysis, the PCT between both T0 and T1 were increased (p < 0.001) and then it decreased till T5.

Conclusions

The use of transparent contact forming instruments achieved greater PCT compared to Palodent sectional matrix system alone that gradually decreased throughout 12 months and reached the PCT between the natural teeth. Using Trimax system provided the tightest proximal contacts. Additionally, digital force gauge was confirmed as an inclusive and accurate method to quantify PCT.

Trial registration

ClinicalTrials.gov NCT05749640: 24/5/2022.
Economic inequalities in decayed, missing, and filled first permanent molars among 8–12 years old Iranian schoolchildren
Authors: Khoramrooz Maryam , Mirrezaie Seyed Mohammad , Emamian Mohammad Hassan , Golbabaei Pasandi Hajar , Dadgari Ali , Hashemi Hassan , Fotouhi Akbar
Published: October 2023

Background

First permanent molars (FPM) play an important role in the masticatory function and oral health. This study aimed to assess the economic inequalities of FPM health indices among schoolchildren in the northeast of Iran.

Methods

A total of 4051 children aged 8–12 years old were included in the analyses of this cross-sectional study in 2015. Economic status was measured using the principal component analysis on home assets. Concentration index (C) was used to measure economic inequality in FPM health indices, and its contributing factors determined by Wagstaff decomposition technique.

Results

The prevalence of having decayed, missing, and filled FPMs among children was 40.9% (95% CI: 38.8–43.0), 1.2% (95% CI: 0.8–1.6%), and 7.8% (95% CI: 6.7–8.9%), respectively. Missing FPM was generally more concentrated among low-economic children (C=-0.158), whereas, filled FPM was more concentrated on high-economic children (C = 0.223). Economic status, mother education, having a housekeeper mother, and overweight/obesity, contributed to the measured inequality in missing FPM by 98.7%, 97.5%, 64.4%, and 11.2%, respectively. Furthermore, 88.9%, 24.1%, 14.5%, and 13.2% of filled FPM inequality was attributable to children’s economic status, father education, residence in rural areas, and age, respectively.

Conclusion

There is a significant economic inequality in both missing and filled FPM. This inequality can be attributed to the economic status of individuals. To reduce FPM extraction, it is important to target low-income and rural children and provide them with FPM restoration services. Additionally, it is necessary to provide training to less-educated parents and housekeeper mothers to address the observed inequalities.
Evaluation of anticancer effect of colchicum autumnale L. Corm on breast cancer cell
Authors: Falahianshafiei Shiva , Akhtari Javad , Davoodi Ali , Pasha Hajar
Published: October 2023

Background

Breast cancer is the most common malignancy in women, and medicinal plants can prevent and play an inhibitory role for cancer. This study aims to evaluate the anticancer effect of colchicum autumnale L. Corm on breast cancer cell models.

Methods

In this study, the alkaloid-rich extract was prepared using the percolation method and with methanol/water solvent (70:30). HFF2 normal cell line and MCF-7 breast cancer cell line were cultured in microplates (96 wells). Then cells were treated with concentrations of 62.5 to 2000 ng/ml of extract and concentrations of 62 to 1000 ng/ml of doxorubicin at regular intervals of 48 and 72 h, and the percentage of cell growth inhibition was calculated. Cytotoxicity of drugs was measured by the MTT assay method. IC50 values were calculated by Calcusyn software. Also, the P-value of < 0.05 was considered significant.

Results

Alkaloid-rich extract of Colchicum autumnale plant inhibited breast cancer cell growth (MCF-7). The IC50 parameter showed more cytotoxic effects of Colchicum autumnale plant extract on the MCF-7 cancer cell line than HFF2 normal cell line for 48 and 72 h. In addition, with higher concentrations of the extract, cytotoxicity, and growth inhibitory effect increased significantly and in comparison to the doxorubicin was almost the same as cytotoxic.

Conclusion

This research provides a novel view into the development of new drugs for the treatment of cancer diseases. Colchicum autumnale plant extract had a significant cytotoxic effect like Doxorubicin drug on breast cancer cell line (MCF-7), which can alternatively treat and prevent breast cancer.
Some new insights into the biological activities of carboxymethylated polysaccharides from Lasiodiplodia theobromae
Authors: Pires Matheus Cerdeira , de Gois Andriolo Natalia , Lopes Bruno Rafael Pereira , Ruiz Ana Lucia Tasca Gois , do Nascimento Valeria Marta Gomes , Toledo Karina Alves , Santos Catarina dos
Published: October 2023

Background

Carboxymethylated Lasiodiplodan (LaEPS-C), Lasiodiplodia theobromae β-glucan exopolysaccharide derivative, has a well-known range of biological activities. Compared to LaEPS-C, its fractions, Linear (LLaEPS-C) and Branched (BLaEPS-C), have biological potentialities scarcely described in the literature. So, in this study, we investigate the immunomodulatory, antiviral, antiproliferative, and anticoagulant activities of LLaEPS-C and BLaEPS-C and compare them to the LaEPS-C.

Methods

LaEPS was obtained from L. theobromae MMBJ. After carboxymethylation, LaEPS-C structural characteristics were confirmed by Elementary Composition Analysis by Energy Dispersive X-Ray Detector (EDS), Fourier Transform Infrared (FTIR), and Nuclear Magnetic Resonance (NMR). The immunomodulatory activity on cytokine secretion was evaluated in human monocyte-derived macrophage cultures. The antiviral activity was evaluated by Hep-2 cell viability in the presence or absence of hRSV (human respiratory syncytial virus). In vitro antiproliferative activity was tested by sulforhodamine B assay. The anticoagulant activity was determined by APTT (Activated Partial Thromboplastin Time) and PT (Prothrombin Time).

Results

LaEPS-C showed low macrophage cell viability only at 100 µg/mL (52.84 ± 24.06, 48 h), and LLaEPS-C presented no effect. Conversely, BLaEPS-C showed cytotoxicity from 25 to 100 µg/mL (44.36 ± 20.16, 40.64 ± 25.55, 33.87 ± 25.16; 48 h). LaEPS-C and LLaEPS-C showed anti-inflammatory activity. LaEPS-C presented this at 100 µg/mL (36.75 ± 5.53, 48 h) for IL-10, and LLaEPS-C reduces TNF-α cytokine productions at 100 µg/mL (18.27 ± 5.80, 48 h). LLaEPS-C showed an anti-hRSV activity (0.7 µg/ml) plus a low cytotoxic activity for Hep-2 cells (1.4 µg/ml). LaEPS-C presented an antiproliferative activity for NCI-ADR/RES (GI50 65.3 µg/mL). A better PT was achieved for LLaEPS-C at 5.0 µg/mL (11.85 ± 0.87s).

Conclusions

These findings demonstrated that carboxymethylation effectively improves the biological potential of the LaEPS-C and their fractions. From those polysaccharides tested, LLaEPS provided the best results with low toxicity for anti-inflammatory, antiviral, and anticoagulant activities.
mRNA-based vaccines and therapeutics: an in-depth survey of current and upcoming clinical applications
Authors: Wang Yu-Shiuan , Kumari Monika , Chen Guan-Hong , Hong Ming-Hsiang , Yuan Joyce Pei-Yi , Tsai Jui-Ling , Wu Han-Chung
Published: October 2023

mRNA-based drugs have tremendous potential as clinical treatments, however, a major challenge in realizing this drug class will promise to develop methods for safely delivering the bioactive agents with high efficiency and without activating the immune system. With regard to mRNA vaccines, researchers have modified the mRNA structure to enhance its stability and promote systemic tolerance of antigenic presentation in non-inflammatory contexts. Still, delivery of naked modified mRNAs is inefficient and results in low levels of antigen protein production. As such, lipid nanoparticles have been utilized to improve delivery and protect the mRNA cargo from extracellular degradation. This advance was a major milestone in the development of mRNA vaccines and dispelled skepticism about the potential of this technology to yield clinically approved medicines. Following the resounding success of mRNA vaccines for COVID-19, many other mRNA-based drugs have been proposed for the treatment of a variety of diseases. This review begins with a discussion of mRNA modifications and delivery vehicles, as well as the factors that influence administration routes. Then, we summarize the potential applications of mRNA-based drugs and discuss further key points pertaining to preclinical and clinical development of mRNA drugs targeting a wide range of diseases. Finally, we discuss the latest market trends and future applications of mRNA-based drugs.
Hardship financing, productivity loss, and the economic cost of illness and injury in Cambodia
Authors: Kolesar Robert John , Erreygers Guido , Van Damme Wim , Chea Vanara , Choeurng Theany , Leng Soklong
Published: October 2023

Background

Financial risk protection is a core dimension of universal health coverage. Hardship financing, defined as borrowing and selling land or assets to pay for healthcare, is a measure of last recourse. Increasing indebtedness and high interest rates, particularly among unregulated money lenders, can lead to a vicious cycle of poverty and exacerbate inequity.

Methods

To inform efforts to improve Cambodia’s social health protection system we analyze 2019–2020 Cambodia Socio-economic Survey data to assess hardship financing, illness and injury related productivity loss, and estimate related economic impacts. We apply two-stage Instrumental Variable multiple regression to address endogeneity relating to net income. In addition, we calculate a direct economic measure to facilitate the regular monitoring and reporting on the devastating burden of excessive out-of-pocket expenditure for policy makers.

Results

More than 98,500 households or 2.7% of the total population resorted to hardship financing over the past year. Factors significantly increasing risk are higher out-of-pocket healthcare expenditures, illness or injury related productivity loss, and spending of savings. The economic burden from annual lost productivity from illness or injury amounts to US$ 459.9 million or 1.7% of GDP. The estimated household economic cost related to hardship financing is US$ 250.8 million or 0.9% of GDP.

Conclusions

Such losses can be mitigated with policy measures such as linking a catastrophic health coverage mechanism to the Health Equity Funds, capping interest rates on health-related loans, and using loan guarantees to incentivize microfinance institutions and banks to refinance health-related, high-interest loans from money lenders. These measures could strengthen social health protection by enhancing financial risk protection, mitigating vulnerability to the devastating economic effects of health shocks, and reducing inequities.
Preservation vs. dissection of inferior pulmonary ligament for thoracoscopic upper lobectomy: a prospective randomized controlled trial
Authors: Qian Jiekun , Cai Shixian , Lin Pinghua , Chi Wanzhong , Chen Chun , Xu Guobin , Xu Chi , Wu Weidong , Zheng Wei , Zheng Bin
Published: October 2023

Objectives

The proper procedure for inferior pulmonary ligament (IPL) during upper lobectomy remains a topic of debate. To address this matter, we carried out a trial comparing the clinical outcomes of IPL preservation versus IPL dissection during thoracoscopic upper lobectomy (TUL).

Methods

Patients undergoing thoracoscopic left/right upper lobectomy (TLUL/TRUL) were assigned to either the dissection group (Group D) or the preservation group (Group P). Our primary objective was to quantify and compare the alterations in postoperative residual bronchial angle and lung volume changes between the two groups. Our secondary objective encompassed the assessment of various other intraoperative and postoperative outcomes.

Results

Following adherence to the inclusion and exclusion criteria, we enrolled 100 patients (41 left and 59 right) in Group P and 108 patients (41 left and 67 right) in Group D for the study. Our findings revealed that in TLUL, Group P was able to reduce the degree of postoperative residual bronchial angle change (P < 0.05). Conversely, the situation was distinct for TRUL. We found no notable disparity between the two groups (P > 0.05) with regard to alterations in lung volume or the occurrence of postoperative complications—except for the duration of postoperative hospital stay (P < 0.05).

Conclusions

Our study suggests IPL preservation especially for TLUL when compared to TRUL, which have important implications for the clinical management of patients undergoing upper lobectomy.
Supporting patients in the transition to the revised pexidartinib dosing regimen: perspectives from the multidisciplinary clinical and allied health professional team
Authors: McCabe Colleen , Wright Hillary , Polson Kathleen , Wagner Andrew J.
Published: October 2023

Pexidartinib is a colony-stimulating factor-1 receptor inhibitor approved in the United States for treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery. Because of the risk of severe and potentially fatal hepatotoxicity, pexidartinib is only available through a Risk Evaluation and Mitigation Strategy (REMS) program. Pexidartinib pharmacokinetics are influenced by the fat content of meals: compared with the fasted state, consuming a high-fat meal with pexidartinib increases pexidartinib absorption by 100%; a low-fat meal increases absorption by approximately 60%. Pexidartinib was initially authorized to be taken at 800 mg/day on an empty stomach; therefore, if this same dose of pexidartinib is taken with food, there is a risk of overexposure and potential toxicity. To reduce the risk of hepatotoxicity and improve patient compliance, pexidartinib has undergone a revised dosing regimen, from 800 mg/day (400 mg twice daily) fasted to 500 mg/day (250 mg twice daily) with a low-fat meal (approximately 11–14 g of total fat). The objective of this report is to educate clinical and allied health professionals on the revised dosing regimen and the importance of patient compliance with a low-fat meal. Healthcare professionals need to understand the rationale for the switch from pexidartinib dosing on an empty stomach to dosing with a low-fat meal and how meal composition and timing influence pharmacokinetics. Finally, we provide guidance for the healthcare team of prescribing providers, nurses, pharmacists, and dietitians who are caring for patients with TGCT on pexidartinib. It is important for healthcare providers to deliver consistent messaging on the low-fat meal requirement and help patients fit pexidartinib into their regular meal schedules. Consulting a dietitian may be helpful for patients, especially those with complex dietary needs. We provide an overview of the roles and responsibilities of each healthcare professional and outline steps to best support patients, including key questions and answers related to the revised dosing regimen. This report provides the information necessary to guide the multidisciplinary team caring for patients with TGCT and to support them through the pexidartinib dosing regimen change.
Integrative multi-omic sequencing reveals the MMTV-Myc mouse model mimics human breast cancer heterogeneity
Authors: Broeker Carson D. , Ortiz Mylena M. O. , Murillo Michael S. , Andrechek Eran R.
Published: October 2023

Background

Breast cancer is a complex and heterogeneous disease with distinct subtypes and molecular profiles corresponding to different clinical outcomes. Mouse models of breast cancer are widely used, but their relevance in capturing the heterogeneity of human disease is unclear. Previous studies have shown the heterogeneity at the gene expression level for the MMTV-Myc model, but have only speculated on the underlying genetics.

Methods

Tumors from the microacinar, squamous, and EMT histological subtypes of the MMTV-Myc mouse model of breast cancer underwent whole genome sequencing. The genomic data obtained were then integrated with previously obtained matched sample gene expression data and extended to additional samples of each histological subtype, totaling 42 gene expression samples. High correlation was observed between genetic copy number events and resulting gene expression by both Spearman’s rank correlation coefficient and the Kendall rank correlation coefficient. These same genetic events are conserved in humans and are indicative of poor overall survival by Kaplan–Meier analysis. A supervised machine learning algorithm trained on METABRIC gene expression data was used to predict the analogous human breast cancer intrinsic subtype from mouse gene expression data.

Results

Herein, we examine three common histological subtypes of the MMTV-Myc model through whole genome sequencing and have integrated these results with gene expression data. Significantly, key genomic alterations driving cell signaling pathways were well conserved within histological subtypes. Genomic changes included frequent, co-occurring mutations in KIT and RARA in the microacinar histological subtype as well as SCRIB mutations in the EMT subtype. EMT tumors additionally displayed strong KRAS activation signatures downstream of genetic activating events primarily ascribed to KRAS activating mutations, but also FGFR2 amplification. Analogous genetic events in human breast cancer showed stark decreases in overall survival. In further analyzing transcriptional heterogeneity of the MMTV-Myc model, we report a supervised machine learning model that classifies MMTV-Myc histological subtypes and other mouse models as being representative of different human intrinsic breast cancer subtypes.

Conclusions

We conclude the well-established MMTV-Myc mouse model presents further opportunities for investigation of human breast cancer heterogeneity.
Drosophila CASK regulates brain size and neuronal morphogenesis, providing a genetic model of postnatal microcephaly suitable for drug discovery
Authors: Tello Judith A. , Jiang Linan , Zohar Yitshak , Restifo Linda L.
Published: October 2023

Background

CASK-related neurodevelopmental disorders are untreatable. Affected children show variable severity, with microcephaly, intellectual disability (ID), and short stature as common features. X-linked human CASK shows dosage sensitivity with haploinsufficiency in females. CASK protein has multiple domains, binding partners, and proposed functions at synapses and in the nucleus. Human and Drosophila CASK show high amino-acid-sequence similarity in all functional domains. Flies homozygous for a hypomorphic CASK mutation (∆18) have motor and cognitive deficits. A Drosophila genetic model of CASK-related disorders could have great scientific and translational value.

Methods

We assessed the effects of CASK loss of function on morphological phenotypes in Drosophila using established genetic, histological, and primary neuronal culture approaches. NeuronMetrics software was used to quantify neurite-arbor morphology. Standard nonparametric statistics methods were supplemented by linear mixed effects modeling in some cases. Microfluidic devices of varied dimensions were fabricated and numerous fluid-flow parameters were used to induce oscillatory stress fields on CNS tissue. Dissociation into viable neurons and neurite outgrowth in vitro were assessed.

Results

We demonstrated that ∆18 homozygous flies have small brains, small heads, and short bodies. When neurons from developing CASK-mutant CNS were cultured in vitro, they grew small neurite arbors with a distinctive, quantifiable “bushy” morphology that was significantly rescued by transgenic CASK+. As in humans, the bushy phenotype showed dosage-sensitive severity. To overcome the limitations of manual tissue trituration for neuronal culture, we optimized the design and operation of a microfluidic system for standardized, automated dissociation of CNS tissue into individual viable neurons. Neurons from CASK-mutant CNS dissociated in the microfluidic system recapitulate the bushy morphology. Moreover, for any given genotype, device-dissociated neurons grew larger arbors than did manually dissociated neurons. This automated dissociation method is also effective for rodent CNS.

Conclusions

These biological and engineering advances set the stage for drug discovery using the Drosophila model of CASK-related disorders. The bushy phenotype provides a cell-based assay for compound screening. Nearly a dozen genes encoding CASK-binding proteins or transcriptional targets also have brain-development mutant phenotypes, including ID. Hence, drugs that improve CASK phenotypes might also benefit children with disorders due to mutant CASK partners.
Transurethral laser lithotripsy using the Mitrofanoff urethral conduit for bladder stones: a case report
Authors: Yamamoto Shotaro , Kawahara Takashi , Saito Tomoki , Hanai Takahiro , Takeshima Teppei , Teranishi Junichi , Makiyama Kazuhide , Uemura Hiroji
Published: October 2023

Background

The Mitrofanoff (appendicovesicostomy) procedure is a contraindicated urinary modification that maintains urinary continence by forming a flap-valve mechanism at the site of anastomosis between the appendage and bladder wall, which is used as a guide for urinary drainage. This technique has been used by intermittent self-catheterization patients who have difficulty voiding from the native urethra or in cases where voiding from the abdominal wall would improve quality of life. However, the risk of stone formation is high due to intermittent urinary catheterization using the Mitrofanoff conduit urethrostomy as a conduit.

Case presentation

The patient was a 22-year-old Asian-Japanese woman. At 6 years of age, she underwent bilateral vesicoureteral reflux surgery, Mitrofanoff urethrostomy using the appendix, abdominal wall plication, and vaginoplasty using the ileum. During follow-up, ultrasound performed due to persistent pain during urinary drainage revealed a 26 mm bladder stone. We performed ureteroscopic lithotripsy 6Fr using ureteral access sheath and made lithotripsy using Ho: YAG laser, then successfully removed the target stone.

Conclusions

We report a case of transurethral laser lithotripsy using the Mitrofanoff urethral conduit for bladder stones. Using with ureteral access sheath made lithotripsy and retrieved ureteral stone more effective.
Lung erosion following adjuvant immunotherapy with pembrolizumab: a case report
Authors: Leow Lowell , Anbudurai Manisha , Yue Li , Tam John Kit Chung
Published: October 2023

Background

Pembrolizumab as immunotherapy is increasingly used in adjuvant, neoadjuvant, and standalone therapy and has been described as safe. We share an experience of lung erosion post-thoracic surgery with the use of adjuvant pembrolizumab.

Case presentation

A 65-year-old Chinese gentleman with metastatic renal cell carcinoma underwent lung metastasis resection and presented with delayed onset pneumothorax while on adjuvant pembrolizumab. Failure of conservative management warranted repeat surgical intervention, and intraoperative findings showed erosion of staple lines possibly caused by poor healing associated with pembrolizumab.

Conclusion

Adjuvant pembrolizumab may impair wound healing, including stapler line healing. Presentation of delayed pneumothorax in a post-surgical patient undergoing immunotherapy should warrant early surgical intervention.
An acoustic echo canceller optimized for hands-free speech telecommunication in large vehicle cabins
Authors: Saremi Amin , Ramkumar Balaji , Ghaffari Ghazaleh , Gu Zonghua
Published: October 2023

Acoustic echo cancelation (AEC) is a system identification problem that has been addressed by various techniques and most commonly by normalized least mean square (NLMS) adaptive algorithms. However, performing a successful AEC in large commercial vehicles has proved complicated due to the size and challenging variations in the acoustic characteristics of their cabins. Here, we present a wideband fully linear time domain NLMS algorithm for AEC that is enhanced by a statistical double-talk detector (DTD) and a voice activity detector (VAD). The proposed solution was tested in four main Volvo truck models, with various cabin geometries, using standard Swedish hearing-in-noise (HINT) sentences in the presence and absence of engine noise. The results show that the proposed solution achieves a high echo return loss enhancement (ERLE) of at least 25 dB with a fast convergence time, fulfilling ITU G.168 requirements. The presented solution was particularly developed to provide a practical compromise between accuracy and computational cost to allow its real-time implementation on commercial digital signal processors (DSPs). A real-time implementation of the solution was coded in C on an ARM Cortex M-7 DSP. The algorithmic latency was measured at less than 26 ms for processing each 50-ms buffer indicating the computational feasibility of the proposed solution for real-time implementation on common DSPs and embedded systems with limited computational and memory resources. MATLAB source codes and related audio files are made available online for reference and further development.
Implementation strategies, facilitators, and barriers to scaling up and sustaining task-sharing in family planning: a protocol for a mixed-methods systematic review
Authors: Aderoba Adeniyi Kolade , Kabra Rita , Kiarie James Njogu
Published: October 2023

Background

Ensuring access to quality family planning (FP) services is fundamental to achieving the Sustainable Development Goals (SDG) targets 3.1, 3.7, and 5.6, including universal access to reproductive health services. However, barriers such as health workforce shortages and restrictive policies on the role of mid and lower-level health workforce cadres limit access to contraceptives and FP in many settings.

Workforce reorganization makes more efficient use of human resources. Consequently, the World Health Organization (WHO) recommends task-sharing for FP by different cadres. Evidence on the implementation strategies, facilitators, and barriers to scaling up and sustaining task-sharing could inform financing, implementation approaches, and technical assistance of national and global FP task-sharing programs. Therefore, this study aims to describe and assess the quality of the evidence on implementation strategies, facilitators, and barriers to scaling up and sustaining task-sharing in FP and the outcome of the scale-up/sustainability interventions.

Methods

This systematic review protocol was developed using relevant guidelines, including the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Protocols (PRISMA-P). A search of five databases, namely CINAHL (EBSCOhost), EMBASE (OvidSP), Global Health (OvidSP), MEDLINE (OvidSP), and Scopus (www.scopus.com), and gray literature resources will be conducted. Two independent reviewers will screen and select studies, assess their quality using the “Mixed Methods Appraisal Tool,” and extract data from eligible studies. Publications or articles are eligible if they report implementation strategies, facilitators, or barriers to scaling up/sustainability of task-sharing in FP/contraception or the outcomes of the scale-up/sustainability interventions. A convergent synthesis that integrates qualitative, quantitative, descriptive, and mixed-methods data into one dataset will be used for analysis based on an a priori framework—the Cochrane Effective Practice and Organization of Care (EPOC) taxonomy of the health system framework. Two independent reviewers will assess the quality of evidence using the GRADE-CERQual guideline.

Discussion

To our knowledge, this systematic review of implementation strategies, facilitators, and barriers to scaling up and sustaining task-sharing in family planning is the first in this area. Our rigorous methodology based on up-to-date guidelines can help generate relevant recommendations to support interventions to scale up and sustain task-sharing in family planning.

Systematic review registration

PROSPERO CRD42022339885.
Effectiveness of thyme honey in the management of xerostomia in geriatric patients with end-stage renal disease: a randomized controlled clinical trial with a biochemical assessment
Authors: Ibrahim Suzan S. , Abou-Bakr Asmaa , Ghalwash Dalia M. , Hussein Radwa R.
Published: October 2023

Background

Taking into consideration the value of the oral health condition in geriatric people with end-stage renal disease (ESRD) associated with xerostomia and believing that salivary stimulants or substitutes could potentially be used to manage this condition. This study aimed to evaluate the clinical effectiveness of thyme honey as oral rinse in geriatric patients with ESRD using the subjective dry mouth score as a primary objective and to assess the effect of thyme honey on the salivary nitric oxide level, salivary flow rate, and salivary ph in addition to objective dry mouth score as a secondary objective.

Methods

This was a single blinded randomized controlled trial with two equal arms, the interventional arm (thyme honey oral rinse) and the control arm (saline). Twenty-eight geriatric patients with ESRD undergoing hemodialysis complained of xerostomia were recruited from the renal dialysis center. Patients in both arms followed the same administration protocol either with thyme honey oral rinse or saline. The following clinical parameters (the subjective and objective dry mouth scores, salivary flow rate, salivary ph, and salivary nitric oxide (NO) levels) were evaluated for both groups at different intervals (baseline, 1 week, and 1 month).

Results

In the current study, it was found that both the subjective and objective dry mouth scores were significantly lower after one month of using thyme honey oral rinse (1.86 ± 0.66B) and (2.21 ± 0.43B) respectively, than the control group (3.07 ± 0.73B) and (3.07 ± 0.83B), respectively with a (p < 0.001). Also, the salivary flow rate was significantly higher after one month of using thyme honey oral rinse (1.56 ± 0.51A), than the control group (0.78 ± 0.27A) with a (p < 0.001). For the NO levels, there was a significant increase in measured value after 1 month in the intervention group (p < 0.001), while for the control group the change was not statistically significant (p = 0.166).

Conclusions

The results of the current study have revealed the efficacy of Thyme honey oral rinse in the management of xerostomia in geriatric patients with ESRD.

Trial registration The ClinicalTrials.gov Identifier for this study is NCT05247008.
PandaGUT provides new insights into bacterial diversity, function, and resistome landscapes with implications for conservation
Authors: Huang Guangping , Shi Wenyu , Wang Le , Qu Qingyue , Zuo Zhenqiang , Wang Jinfeng , Zhao Fangqing , Wei Fuwen
Published: October 2023

Background

The gut microbiota play important roles in host adaptation and evolution, but are understudied in natural population of wild mammals. To address host adaptive evolution and improve conservation efforts of threatened mammals from a metagenomic perspective, we established a high-quality gut microbiome catalog of the giant panda (pandaGUT) to resolve the microbiome diversity, functional, and resistome landscapes using approximately 7 Tbp of long- and short-read sequencing data from 439 stool samples.

Results

The pandaGUT catalog comprises 820 metagenome-assembled genomes, including 40 complete closed genomes, and 64.5% of which belong to species that have not been previously reported, greatly expanding the coverage of most prokaryotic lineages. The catalog contains 2.37 million unique genes, with 74.8% possessing complete open read frames, facilitating future mining of microbial functional potential. We identified three microbial enterotypes across wild and captive panda populations characterized by Clostridium, Pseudomonas, and Escherichia, respectively. We found that wild pandas exhibited host genetic-specific microbial structures and functions, suggesting host-gut microbiota phylosymbiosis, while the captive cohorts encoded more multi-drug resistance genes.

Conclusions

Our study provides largely untapped resources for biochemical and biotechnological applications as well as potential intervention avenues via the rational manipulation of microbial diversity and reducing antibiotic usage for future conservation management of wildlife.
Improving the accuracy of polar motion prediction using a hybrid least squares and long short-term memory model
Authors: Wang Chenxiang , Zhang Pengfei
Published: October 2023

Earth rotation parameters (ERPs) are essential for transforming between the celestial and terrestrial reference frames, and for high-precision space navigation and positioning. Among the ERPs, polar motion (PM) is a critical parameter for analyzing and understanding the dynamic interaction between the solid Earth, atmosphere, ocean, and other geophysical fluids. Traditional methods for predicting the change in ERPs rely heavily on linear models, such as the least squares (LS) and the autoregressive (AR) model (LS + AR). However, variations in ERP partly reflect non-linear effects in the Earth system, such that the predictive accuracy of linear models is not always optimal. In this paper, long short-term memory (LSTM), a non-linear neural network, is employed to improve the prediction of ERPs. Polar motion prediction experiments in this study are conducted using the LSTM model and a hybrid method LS + LSTM model based on the IERS EOP14C04 time series. Compared with Bulletin A, the PMX and PMY prediction accuracy can reach a maximum of 33.7% and 31.9%, respectively, with the LS + LSTM model. The experimental results show that the proposed hybrid model displays a better performance in mid- and long-term (120–365 days) prediction of polar motion.

Graphical Abstract
Stem cells for the treatment of early to moderate osteoarthritis of the knee: a systematic review
Authors: Kyriakidis Theofylaktos , Pitsilos Charalampos , Iosifidou Myrto , Tzaveas Alexandros , Gigis Ioannis , Ditsios Konstantinos , Iosifidis Michael
Published: October 2023

Purpose

Mesenchymal stem cells (MSCs) present a valuable treatment option for knee osteoarthritis with promising results. The purpose of the present study was to systematically review the clinical and functional outcomes following mesenchymal stem cell application focusing on early to moderate knee osteoarthritis.

Methods

A systematic search was done using the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines in Pubmed, Scopus, Web of Science, and Cochrane Library databases. All Studies published between 2017 and March 2023 on patients treated with single mesenchymal stem cell injection for Kellgren‐Lawrence grade I—III knee osteoarthritis reported on clinical and functional outcomes were included.

Results

Twelve articles comprising 539 patients and 576 knees treated with a single intraarticular injection of MSCs for knee osteoarthritis were included in the current systematic review. In eligible studies, the reported outcomes were improved concerning patient‐reported outcomes measures, knee function, pain relief, and quality of patient's life.

Conclusion

Based on high‐level evidence studies, single intraarticular injection of MSCs is a safe, reliable, and effective treatment option for Kellgren‐Lawrence grade I—III knee osteoarthritis. However, the lack of homogeneity in the included studies and the variance in MSCs sources and preparations should be noted.

Level of evidence

III.