bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and prognostic importance of exercise limitation and physical inactivity in COPD
Authors: Vaes Anouk W. , Burtin Chris , Casaburi Richard , Celli Bartolome R. , Evans Rachael A. , Lareau Suzanne C. , Nici Linda , Rochester Carolyn L. , Troosters Thierry
Published: June 2024

Exercise limitation and physical inactivity are separate, but related constructs. Both are commonly present in individuals with COPD, contribute to disease burden over and above the respiratory impairments, and are independently predictive of adverse outcomes. Because of this, clinicians should consider assessing these variables in their patients with COPD. Field tests of exercise performance such as the 6-min walk test and the incremental and endurance shuttle walk tests require limited additional resources, and results correlate with negative outcomes. Laboratory measures of exercise performance using a treadmill or cycle ergometer assess exercise capacity, provide prognostic information and have the advantage of explaining physiological mechanisms (and their interactions) underpinning exercise limitation. Limitations in exercise capacity (i.e.“cannot do”) and physical inactivity (i.e.“do not do”) are both associated with mortality; exercise limitation appears to be the more important driver of this outcome.
Prediction of the future number of fall-related emergency medical services calls in older individuals
Authors: Uemura Shuji , Nakayama Ryuichi , Koyama Masayuki , Taguchi Yukiko , Bunya Naofumi , Sawamoto Keigo , Ohnishi Hirofumi , Narimatsu Eichi
Published: June 2024

Background

Falls among older individuals contribute significantly to the rise in ambulance transport use. To recognize the importance of future countermeasures, we estimated the projected number and percentage of fall-related emergency medical service (EMS) calls.

Methods

We examined the sex, age group, and location of falls among patients aged ≥ 65 years who contacted emergency services in Sapporo City from 2013 to 2021. Annual fall-related calls per population subgroup were calculated, and trends were analyzed. Four models were used to estimate the future number of fall-related calls from the 2025–2060 projected population: (1) based on the 2022 data, estimates from the 2013–2022 data using (2) Poisson progression, (3) neural network, (4) estimates from the 2013–2019 data using neural network. The number of all EMS calls was also determined using the same method to obtain the ratio of all EMS calls.

Results

During 2013–2022, 70,262 fall-related calls were made for those aged ≥ 65 years. The rate was higher indoors among females and outdoor among males in most age groups and generally increased with age. After adjusting for age, the rate increased by year. Future estimates of the number of fall calls are approximately double the number in 2022 in 2040 and three times in 2060, with falls accounting for approximately 11% and 13% of all EMS calls in 2040 and 2060, respectively.

Conclusion

The number of fall-related EMS calls among older people is expected to increase in the future, and the percentage of EMS calls will also increase; therefore, countermeasures are urgently needed.
Drug repurposing based on the DTD-GNN graph neural network: revealing the relationships among drugs, targets and diseases
Authors: Li Wenjun , Ma Wanjun , Yang Mengyun , Tang Xiwei
Published: June 2024

Motivation

The rational modelling of the relationship among drugs, targets and diseases is crucial for drug retargeting. While significant progress has been made in studying binary relationships, further research is needed to deepen our understanding of ternary relationships. The application of graph neural networks in drug retargeting is increasing, but further research is needed to determine the appropriate modelling method for ternary relationships and how to capture their complex multi-feature structure.

Results

The aim of this study was to construct relationships among drug, targets and diseases. To represent the complex relationships among these entities, we used a heterogeneous graph structure. Additionally, we propose a DTD-GNN model that combines graph convolutional networks and graph attention networks to learn feature representations and association information, facilitating a more thorough exploration of the relationships. The experimental results demonstrate that the DTD-GNN model outperforms other graph neural network models in terms of AUC, Precision, and F1-score. The study has important implications for gaining a comprehensive understanding of the relationships between drugs and diseases, as well as for further research and application in exploring the mechanisms of drug-disease interactions. The study reveals these relationships, providing possibilities for innovative therapeutic strategies in medicine.
Whole transcriptome analysis to identify non-coding RNA regulators and hub genes in sperm of non-obstructive azoospermia by microarray, single-cell RNA sequencing, weighted gene co-expression network analysis, and mRNA-miRNA-lncRNA interaction analysis
Authors: Karoii Danial Hashemi , Azizi Hossein , Skutella Thomas
Published: June 2024

Background

The issue of male fertility is becoming increasingly common due to genetic differences inherited over generations. Gene expression and evaluation of non-coding RNA (ncRNA), crucial for sperm development, are significant factors. This gene expression can affect sperm motility and, consequently, fertility. Understanding the intricate protein interactions that play essential roles in sperm differentiation and development is vital. This knowledge could lead to more effective treatments and interventions for male infertility.

Materials and methods

Our research aim to identify new and key genes and ncRNA involved in non-obstructive azoospermia (NOA), improving genetic diagnosis and offering more accurate estimates for successful sperm extraction based on an individual’s genotype.

Results

We analyzed the transcript of three NOA patients who tested negative for genetic sperm issues, employing comprehensive genome-wide analysis of approximately 50,000 transcript sequences using microarray technology. This compared gene expression profiles between NOA sperm and normal sperm. We found significant gene expression differences: 150 genes were up-regulated, and 78 genes were down-regulated, along with 24 ncRNAs up-regulated and 13 ncRNAs down-regulated compared to normal conditions. By cross-referencing our results with a single-cell genomics database, we identified overexpressed biological process terms in differentially expressed genes, such as “protein localization to endosomes” and “xenobiotic transport.” Overrepresented molecular function terms in up-regulated genes included “voltage-gated calcium channel activity,” “growth hormone-releasing hormone receptor activity,” and “sialic acid transmembrane transporter activity.” Analysis revealed nine hub genes associated with NOA sperm: RPL34, CYB5B, GOL6A6, LSM1, ARL4A, DHX57, STARD9, HSP90B1, and VPS36.

Conclusions

These genes and their interacting proteins may play a role in the pathophysiology of germ cell abnormalities and infertility.
Transcriptome and metabolome analysis reveals mechanism of light intensity modulating iridoid biosynthesis in Gentiana macrophylla Pall.
Authors: Fu Huanhuan , Wang Yaomin , Mi Fakai , Wang Li , Yang Ye , Wang Fang , Yue Zhenggang , He Yihan
Published: June 2024

Light intensity is a key factor affecting the synthesis of secondary metabolites in plants. However, the response mechanisms of metabolites and genes in Gentiana macrophylla under different light intensities have not been determined. In the present study, G. macrophylla seedlings were treated with LED light intensities of 15 µmol/m2/s (low light, LL), 90 µmol/m2/s (medium light, ML), and 200 µmol/m2/s (high light, HL), and leaves were collected on the 5th day for further investigation. A total of 2162 metabolites were detected, in which, the most abundant metabolites were identified as flavonoids, carbohydrates, terpenoids and amino acids. A total of 3313 and 613 differentially expressed genes (DEGs) were identified in the LL and HL groups compared with the ML group, respectively, mainly enriched in KEGG pathways such as carotenoid biosynthesis, carbon metabolism, glycolysis/gluconeogenesis, amino acids biosynthesis, plant MAPK pathway and plant hormone signaling. Besides, the transcription factors of GmMYB5 and GmbHLH20 were determined to be significantly correlated with loganic acid biosynthesis; the expression of photosystem-related enzyme genes was altered under different light intensities, regulating the expression of enzyme genes involved in the carotenoid, chlorophyll, glycolysis and amino acids pathway, then affecting their metabolic biosynthesis. As a result, low light inhibited photosynthesis, delayed glycolysis, thus, increased certain amino acids and decreased loganic acid production, while high light got an opposite trend. Our research contributed significantly to understand the molecular mechanism of light intensity in controlling metabolic accumulation in G. macrophylla.
Combining transcriptome and metabolome analysis to understand the response of sorghum to Melanaphis sacchari
Authors: Zhao Xin-Rui , Zhao Dong-Ting , Zhang Ling-Yu , Chang Jin-Hua , Cui Jiang-Hui
Published: June 2024

Background

The sorghum aphid Melanaphis sacchari (Zehntner) (Homoptera: Aphididae) is an important insect in the late growth phase of sorghum (Sorghum bicolor L.). However, the mechanisms of sorghum response to aphid infestation are unclear.

Results

In this paper, the mechanisms of aphid resistance in different types of sorghum varieties were revealed by studying the epidermal cell structure and performing a transcriptome and metabolome association analysis of aphid-resistant and aphid-susceptible varieties. The epidermal cell results showed that the resistance of sorghum to aphids was positively correlated with epidermal cell regularity and negatively correlated with the intercellular space and leaf thickness. Transcriptome and metabolomic analyses showed that differentially expressed genes in the resistant variety HN16 and susceptible variety BTX623 were mainly enriched in the flavonoid biosynthesis pathway and differentially expressed metabolites were mainly related to isoflavonoid biosynthesis and flavonoid biosynthesis. The q-PCR results of key genes were consistent with the transcriptome expression results. Meanwhile, the metabolome test results showed that after aphidinfestation, naringenin and genistein were significantly upregulated in the aphid-resistant variety HN16 and aphid-susceptible variety BTX623 while luteolin was only significantly upregulated in BTX623. These results show that naringenin, genistein, and luteolin play important roles in plant resistance to aphid infestation. The results of exogenous spraying tests showed that a 1‰ concentration of naringenin and genistein is optimal for improving sorghum resistance to aphid feeding.

Conclusions

In summary, the physical properties of the sorghum leaf structure related to aphid resistance were studied to provide a reference for the breeding of aphid-resistant varieties. The flavonoid biosynthesis pathway plays an important role in the response of sorghum aphids and represents an important basis for the biological control of these pests. The results of the spraying experiment provide insights for developing anti-aphid substances in the future.
Response surface methodology mediated optimization of phytosulfokine and plant growth regulators for enhanced protoplast division, callus induction, and somatic embryogenesis in Angelica Gigas Nakai
Authors: Lee Han-Sol , Han Jong-Eun , Bae Eun-Kyung , Jie Eun Yee , Kim Suk Weon , Kwon Hyuk Joon , Lee Hak Sung , Yeon Soo-Ho , Murthy Hosakatte Niranjana , Park So-Young
Published: June 2024

Background

Angelica Gigas(Purple parsnip) is an important medicinal plant that is cultivated and utilized in Korea, Japan, and China. It contains bioactive substances especially coumarins with anti-inflammatory, anti-platelet aggregation, anti-cancer, anti-diabetic, antimicrobial, anti-obesity, anti-oxidant, immunomodulatory, and neuroprotective properties. This medicinal crop can be genetically improved, and the metabolites can be obtained by embryonic stem cells. In this context, we established the protoplast-to-plant regeneration methodology inAngelica gigas.

Results

In the present investigation, we isolated the protoplast from the embryogenic callus by applying methods that we have developed earlier and established protoplast cultures using Murashige and Skoog (MS) liquid medium and by embedding the protoplast in thin alginate layer (TAL) methods. We supplemented the culture medium with growth regulators namely 2,4-dichlorophenoxyaceticacid (2,4-D, 0, 0.75, 1.5 mg L− 1), kinetin (KN, 0, 0.5, and 1.0 mg L− 1) and phytosulfokine (PSK, 0, 50, 100 nM) to induce protoplast division, microcolony formation, and embryogenic callus regeneration. We applied central composite design (CCD) and response surface methodology (RSM) for the optimization of 2,4-D, KN, and PSK levels during protoplast division, micro-callus formation, and induction of embryogenic callus stages. The results revealed that 0.04 mg L− 12,4-D + 0.5 mg L− 1KN + 2 nM PSK, 0.5 mg L− 12,4-D + 0.9 mg L− 1KN and 90 nM PSK, and 1.5 mg L− 12,4-D and 1 mg L− 1KN were optimum for protoplast division, micro-callus formation and induction embryogenic callus. MS basal semi-solid medium without growth regulators was good for the development of embryos and plant regeneration.

Conclusions

This study demonstrated successful protoplast culture, protoplast division, micro-callus formation, induction embryogenic callus, somatic embryogenesis, and plant regeneration inA. gigas. The methodologies developed here are quite useful for the genetic improvement of this important medicinal plant.
Barriers and enablers to improving integrated primary healthcare for non-communicable diseases and mental health conditions in Ethiopia: a mixed methods study
Authors: Bekele Alemayehu , Alem Atalay , Seward Nadine , Eshetu Tigist , Gebremariam Tewodros Haile , Getachew Yeneneh , Mengiste Wondosen , Medhin Girmay , Fairall Lara , Sevdalis Nick , Prince Martin , Fekadu Abebaw , Hanlon Charlotte
Published: June 2024

Background

The Ethiopian Primary Healthcare Clinical Guidelines (EPHCG) seek to improve quality of primary health care, while also expanding access to care for people with Non-Communicable Diseases and Mental Health Conditions (NCDs/MHCs). The aim of this study was to identify barriers and enablers to implementation of the EPHCG with a particular focus on NCDs/MHCs.

Methods

A mixed-methods convergent-parallel design was employed after EPHCG implementation in 18 health facilities in southern Ethiopia. Semi-structured interviews were conducted with 10 primary healthcare clinicians and one healthcare administrator. Organisational Readiness for Implementing Change (ORIC) questionnaire was self-completed by 124 health workers and analysed using Kruskal Wallis ranked test to investigate median score differences. Qualitative data were mapped to the Consolidated Framework for Implementation Science (CFIR) and the Theoretical Domains Framework (TDF). Expert Recommendations for Implementing Change (ERIC) were employed to select implementation strategies to address barriers.

Results

Four domains were identified: EPHCG training and implementation, awareness and meeting patient needs (demand side), resource constraints/barriers (supply side) and care pathway bottlenecks. The innovative facility-based training to implement EPHCG had a mixed response, especially in busy facilities where teams reported struggling to find protected time to meet. Key barriers to implementation of EPHCG were non-availability of resources (CFIR inner setting), such as laboratory reagents and medications that undermined efforts to follow guideline-based care, the way care was structured and lack of familiarity with providing care for people with NCDs-MHCs. Substantial barriers arose because of socio-economic problems that were interlinked with health but not addressable within the health system (CFIR outer setting). Other factors influencing effective implementation of EPHCG (TDF) included low population awareness about NCDs/MHCs and unaffordable diagnostic and treatment services (TDF). Implementation strategies were identified. ORIC findings indicated high scores of organisational readiness to implement the desired change with likely social desirability bias.

Conclusion

Although perceived as necessary, practical implementation of EPHCG was constrained by challenges across domains of internal/external determinants. This was especially marked in relation to expansion of care responsibilities to include NCDs/MHCs. Attention to social determinants of health outcomes, community engagement and awareness-raising are needed to maximize population impact.
Artificial intelligence-driven computer aided diagnosis system provides similar diagnosis value compared with doctors’ evaluation in lung cancer screening
Authors: Gao Shan , Xu Zexuan , Kang Wanli , Lv Xinna , Chu Naihui , Xu Shaofa , Hou Dailun
Published: June 2024

Objective

To evaluate the consistency between doctors and artificial intelligence (AI) software in analysing and diagnosing pulmonary nodules, and assess whether the characteristics of pulmonary nodules derived from the two methods are consistent for the interpretation of carcinomatous nodules.

Materials and Methods

This retrospective study analysed participants aged 40–74 in the local area from 2011 to 2013. Pulmonary nodules were examined radiologically using a low-dose chest CT scan, evaluated by an expert panel of doctors in radiology, oncology, and thoracic departments, as well as a computer-aided diagnostic(CAD) system based on the three-dimensional(3D) convolutional neural network (CNN) with DenseNet architecture(InferRead CT Lung, IRCL). Consistency tests were employed to assess the uniformity of the radiological characteristics of the pulmonary nodules. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic accuracy. Logistic regression analysis is utilized to determine whether the two methods yield the same predictive factors for cancerous nodules.

Results

A total of 570 subjects were included in this retrospective study. The AI software demonstrated high consistency with the panel's evaluation in determining the position and diameter of the pulmonary nodules (kappa = 0.883, concordance correlation coefficient (CCC) = 0.809, p = 0.000). The comparison of the solid nodules' attenuation characteristics also showed acceptable consistency (kappa = 0.503). In patients diagnosed with lung cancer, the area under the curve (AUC) for the panel and AI were 0.873 (95%CI: 0.829–0.909) and 0.921 (95%CI: 0.884–0.949), respectively. However, there was no significant difference (p = 0.0950). The maximum diameter, solid nodules, subsolid nodules were the crucial factors for interpreting carcinomatous nodules in the analysis of expert panel and IRCL pulmonary nodule characteristics.

Conclusion

AI software can assist doctors in diagnosing nodules and is consistent with doctors' evaluations and diagnosis of pulmonary nodules.
Clinical application of intraoperative ultrasound superb microvascular imaging in brain tumors resections: contributing to the achievement of total tumoral resection
Authors: Cai Siman , Xing Hao , Wang Yuekun , Wang Yu , Ma Wenbin , Jiang Yuxin , Li Jianchu , Wang Hongyan
Published: June 2024

Background

To investigate whether the intraoperative superb microvascular imaging(SMI) technique helps evaluate lesion boundaries compared with conventional grayscale ultrasound in brain tumor surgery and to explore factors that may be associated with complete radiographic resection.

Methods

This study enrolled 57 consecutive brain tumor patients undergoing surgery. During the operation, B-mode and SMI ultrasound evaluated the boundaries of brain tumors. MRI before and within 48h after surgery was used as the gold standard to evaluate gross-total resection(GTR). The ultrasound findings and GTR results were analyzed to determine the imaging factors related to GTR.

Results

A total of 57 patients were enrolled in the study, including 32 males and 25 females, with an average age of 53.4 ± 14.1 years old(range 19 ~ 80). According to the assessment criteria of MRI, before and within 48 h after the operation, 37(63.9%) cases were classified as GTR, and 20(35.1%) cases were classified as GTR. In comparing tumor interface definition between B-mode and SMI mode, SMI improved HGG boundary recognition in 5 cases(P = 0.033). The results showed that the tumor size ≥ 5 cm and unclear ultrasonic boundary were independent risk factors for nGTR (OR>1, P<0.05).

Conclusions

As an innovative intraoperative doppler technique in neurosurgery, SMI can effectively demarcate the tumor’s boundary and help achieve GTR as much as possible.
Development and validation of a LASSO prediction model for cisplatin induced nephrotoxicity: a case-control study in China
Authors: Zhang Jingwei , Luo Xuyang , Fan Yi , Zhou Wei , Ma Shijie , Kang Yuwei , Yang Wei , Geng Xiaoxia , Zhang Heping , Deng Fei
Published: June 2024

Background

Early identification of high-risk individuals with cisplatin-induced nephrotoxicity (CIN) is crucial for avoiding CIN and improving prognosis. In this study, we developed and validated a CIN prediction model based on general clinical data, laboratory indications, and genetic features of lung cancer patients before chemotherapy.

Methods

We retrospectively included 696 lung cancer patients using platinum chemotherapy regimens from June 2019 to June 2021 as the traing set to construct a predictive model using Absolute shrinkage and selection operator (LASSO) regression, cross validation, and Akaike’s information criterion (AIC) to select important variables. We prospectively selected 283 independent lung cancer patients from July 2021 to December 2022 as the test set to evaluate the model’s performance.

Results

The prediction model showed good discrimination and calibration, with AUCs of 0.9217 and 0.8288, sensitivity of 79.89% and 45.07%, specificity of 94.48% and 94.81%, in the training and test sets respectively. Clinical decision curve analysis suggested that the model has value for clinical use when the risk threshold ranges between 0.1 and 0.9. Precision-Recall (PR) curve shown in recall interval from 0.5 to 0.75: precision gradually declines with increasing Recall, up to 0.9.

Conclusions

Predictive models based on laboratory and demographic variables can serve as a beneficial complementary tool for identifying high-risk populations with CIN.
A nomogram for predicting 28-day mortality in elderly patients with acute kidney injury receiving continuous renal replacement therapy: a secondary analysis based on a retrospective cohort study
Authors: Li Xiang , Li Yang , Fan Cheng-Juan , Jiao Zhan-feng , Zhang Yi-Ming , Luo Na-na , Ma Xiao-Fen
Published: June 2024

Background

Acute kidney injury (AKI) is a common and serious condition, particularly among elderly patients. It is associated with high morbidity and mortality rates, further compounded by the need for continuous renal replacement therapy in severe cases. To improve clinical decision-making and patient management, there is a need for accurate prediction models that can identify patients at a high risk of mortality.

Methods

Data were extracted from the Dryad Digital Repository. Multivariate analysis was performed using least absolute shrinkage and selection operator (LASSO) logistic regression analysis to identify independent risk factors and construct a predictive nomogram for mortality within 28 days after continuous renal replacement therapy in elderly patients with acute kidney injury. The discrimination of the model was evaluated in the validation cohort using the area under the receiver operating characteristic curve (AUC), and calibration was evaluated using a calibration curve. The clinical utility of the model was assessed using decision curve analysis (DCA).

Results

A total of 606 participants were enrolled and randomly divided into two groups: a training cohort (n = 424) and a validation cohort (n = 182) in a 7:3 proportion. A risk prediction model was developed to identify independent predictors of 28-day mortality in elderly patients with AKI. The predictors included age, systolic blood pressure, creatinine, albumin, phosphorus, age-adjusted Charlson Comorbidity Index (CCI), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and sequential organ failure assessment (SOFA) score. These predictors were incorporated into a logistic model and presented in a user-friendly nomogram. In the validation cohort, the model demonstrated good predictive performance with an AUC of 0.799. The calibration curve showed that the model was well calibrated. Additionally, DCA revealed significant net benefits of the nomogram for clinical application.

Conclusion

The development of a nomogram for predicting 28-day mortality in elderly patients with AKI receiving continuous renal replacement therapy has the potential to improve prognostic accuracy and assist in clinical decision-making.
Investigating CHRNA5, CHRNA3, and CHRNB4 variants in the genetic landscape of substance use disorder in Jordan
Authors: AL-Eitan Laith , Shatnawi Mohammad , Alghamdi Mansour
Published: June 2024

Background

Substance use disorder (SUD) is a complex illness that can be attributed to the interaction between environmental and genetic factors. The nicotinic receptor gene cluster on chromosome 15 has a plausible association with SUD, particularly with nicotine dependence.

Methods

This study investigated 15 SNPs within the CHRNA5, CHRNA3, and CHRNB4 genes. Sequencing was used for genotyping 495 Jordanian males with SUD and 497 controls matched for age, gender, and descent.

Results

Our findings revealed that none of the tested alleles or genotypes were correlated with SUD. However, our analysis suggests that the route of substance use was linked to rs1051730 (P value = 0.04), rs8040868 (P value = 0.01) of CHRNA3, and rs16969968 (P value = 0.03) of CHRNA5. Additionally, a correlation was identified between rs3813567 of the CHRNB4 gene and the age at substance use onset (P value = 0.04).

Conclusions

Variants in CHRNA5, CHRNA3, and CHRNB4 may interact with SUD features that can influence the development and progression of the disorder among Jordanians.
Sit-to-stand performance in children with cerebral palsy: a population-based cross-sectional study
Authors: Romin Elinor , Lindgren Anna , Rodby-Bousquet Elisabet , Cloodt Erika
Published: June 2024

Background

Sit-to-stand (STS) is one of the most commonly performed functional movements in a child’s daily life that enables the child to perform functional activities such as independent transfer and to initiate walking and self-care. Children with cerebral palsy (CP) often have reduced STS ability. The aim of this study was to describe STS performance in a national based total population of children with CP and its association with age, sex, Gross Motor Function Classification System (GMFCS) level, and CP subtype.

Methods

This cross-sectional study included 4,250 children (2,503 boys, 1,747 girls) aged 1–18 years from the Swedish Cerebral Palsy Follow-Up Program (CPUP). STS performance was classified depending on the independence or need for support into “without support,” “with support,” or “unable.” “With support” included external support from, e.g., walls and furniture. Physical assistance from another person was classified as “unable” (dependent). Ordinal and binary logistic regression analyses were used to identify associations between STS and age, GMFCS level, and CP subtype.

Results

60% of the children performed STS without support, 14% performed STS with support, and 26% were unable or needed assistance from another person. STS performance was strongly associated with GMFCS level and differed with age and subtype (p < 0.001). For all GMFCS levels, STS performance was lowest at age 1–3 years. Most children with GMFCS level I (99%) or II (88%) performed STS without support at the age of 4–6 years. In children with GMFCS level III or IV, the prevalence of independent STS performance improved throughout childhood. CP subtype was not associated with STS performance across all GMFCS levels when adjusted for age.

Conclusions

Independent STS performance in children with CP is associated with GMFCS level and age. Children with CP acquire STS ability later than their peers normally do. The proportion of children with independent STS performance increased throughout childhood, also for children with GMFCS level III or IV. These findings suggest the importance of maintaining a focus on STS performance within physiotherapy strategies and interventions for children with CP, including those with higher GMFCS level.
Screening tools for employment in clinical healthcare delivery systems: a content analysis
Authors: Colon Mina , Goodman Julia M.
Published: June 2024

Background

The relationship between work and health is complex and bidirectional, where work can have both health-harming and health-enhancing effects. Though employment is recognized as a social determinant of health, and clinical healthcare delivery systems are increasingly using screening tools to ask patients about social needs, little research has explored the extent to which employment-related social risk is captured in these screening tools. This study aimed to identify and characterize employment- and work-related questions in social risk screening tools that have been implemented in clinical healthcare delivery systems.

Methods

We conducted a qualitative content analysis of employment-related items in screening tools that have been implemented in clinical healthcare service delivery systems. Three content areas guided data extraction and analysis: Setting, Domain, and Level of Contextualization.

Results

Screening tools that asked employment-related questions were implemented in settings that were diverse in the populations served and the scope of care provided. The intent of employment-related items focused on four domains: Social Risk Factor, Social Need, Employment Exposure, and Legal Need. Most questions were found to have a low Level of Contextualization and were largely focused on identifying an individual’s employment status.

Conclusions

Several existing screening tools include measures of employment-related social risk, but these items do not have a clear purpose and range widely depending on the setting in which they are implemented. In order to maximize the utility of these tools, clinical healthcare delivery systems should carefully consider what domain(s) they aim to capture and how they anticipate using the screening tools to address social determinants of health.
A rapid mixed-methods assessment of Libya’s primary care system
Authors: Allen Luke N. , Hatefi Arian , Kak Mohini , Herbst Christopher H. , Mallender Jacqueline , Karem Ghassan
Published: June 2024

Background

Libya has experienced decades of violent conflict that have severely disrupted health service delivery. The Government of National Unity is committed to rebuilding a resilient health system built on a platform of strong primary care.

Aim

Commissioned by the government, we set out to perform a rapid assessment of the system as it stands and identify areas for improvement.

Design and setting

We used a rapid applied policy explanatory-sequential mixed-methods design, working with Libyan data and Libyan policymakers, with supporting interview data from other primary care policymakers working across the Middle East and North Africa region.

Method

We used the Primary Health Care Performance Initiative framework to structure our assessment. Review of policy documents and secondary analysis of WHO and World Bank survey data informed a series of targeted policymaker interviews. We used deductive framework analysis to synthesise our findings.

Results

We identified 11 key documents and six key policymakers to interview. Libya has strong policy commitments to providing good quality primary care, and a high number of health staff and facilities. Access to services and trust in providers is high. However, a third of facilities are non-operational; there is a marked skew towards axillary and administrative staff; and structural challenges with financing, logistics, and standards has led to highly variable provision of care.

Conclusion

In reforming the primary care system, the government should consolidate leadership, clarify governance structures and systems, and focus on setting national standards for human resources for health, facilities, stocks, and clinical care.
Octanoic acid mitigates busulfan-induced blood-testis barrier damage by alleviating oxidative stress and autophagy
Authors: Cao Chun , Zhang Hong , He Zhaowanyue , Zhang Kemei , Qian Zhang , Shen Jiaming , Zheng Lu , Xue Mengqi , Sun Shanshan , Li Chuwei , Zhao Wei , Jing Jun , Ma Rujun , Ge Xie , Yao Bing
Published: June 2024

Background

The management of male infertility continues to encounter an array of challenges and constraints, necessitating an in-depth exploration of novel therapeutic targets to enhance its efficacy. As an eight-carbon medium-chain fatty acid, octanoic acid (OCA) shows promise for improving health, yet its impact on spermatogenesis remains inadequately researched.

Methods

Mass spectrometry was performed to determine the fatty acid content and screen for a pivotal lipid component in the serum of patients with severe spermatogenesis disorders. The sperm quality was examined, and histopathological analysis and biotin tracer tests were performed to assess spermatogenesis function and the integrity of the blood-testis barrier (BTB) in vivo. Cell-based in vitro experiments were carried out to investigate the effects of OCA administration on Sertoli cell dysfunction. This research aimed to elucidate the mechanism by which OCA may influence the function of Sertoli cells.

Results

A pronounced reduction in OCA content was observed in the serum of patients with severe spermatogenesis disorders, indicating that OCA deficiency is related to spermatogenic disorders. The protective effect of OCA on reproduction was tested in a mouse model of spermatogenic disorder induced by busulfan at a dose 30 mg/kg body weight (BW). The mice in the study were separated into distinct groups and administered varying amounts of OCA, specifically at doses of 32, 64, 128, and 256 mg/kg BW. After evaluating sperm parameters, the most effective dose was determined to be 32 mg/kg BW. In vivo experiments showed that treatment with OCA significantly improved sperm quality, testicular histopathology and BTB integrity, which were damaged by busulfan. Moreover, OCA intervention reduced busulfan-induced oxidative stress and autophagy in mouse testes. In vitro, OCA pretreatment (100 µM) significantly ameliorated Sertoli cell dysfunction by alleviating busulfan (800 µM)-induced oxidative stress and autophagy. Moreover, rapamycin (5 µM)-induced autophagy led to Sertoli cell barrier dysfunction, while OCA administration exerted a protective effect by alleviating autophagy.

Conclusions

This study demonstrated that OCA administration suppressed oxidative stress and autophagy to alleviate busulfan-induced BTB damage. These findings provide a deeper understanding of the toxicology of busulfan and a promising avenue for the development of novel OCA-based therapies for male infertility.
Clinical features and recurrence predictors of histiocytic necrotizing lymphadenitis in Chinese children
Authors: Zhang Xiaoning , Jin Xiuhong , Zhang Xiangfeng , Shen Yuelin
Published: June 2024

Objectives

To characterize the clinical features and to identify the predictors of recurrence of histiocytic necrotizing lymphadenitis (HNL) in Chinese children.

Study design

This study retrospectively analyzed the clinical characteristics, laboratory and pathological findings, and recurrence status of children diagnosed with HNL at a single center in China from January 2018 to May 2023. Logistic regression analysis was employed to identify predictors of HNL recurrence.

Results

181 Chinese children with histopathologically confirmed HNL were enrolled (121 males and 60 females). The mean age was 9.3 ± 2.9 years. The most prominent clinical features were fever (98.9%) and cervical lymphadenopathy (98.3%). Aseptic meningitis was the most frequent complication (38.5%), while hemophagocytic lymphohistiocytosis and autoimmune disease were rare (1.7% and 1.2%, respectively). Recurrence occurred in 12.7% of patients. Erythrocyte sedimentation rate (> 30 mm/h) was the significant predictors of HNL recurrence, with odds ratios of 6.107, respectively.

Conclusion

Our study demonstrates that fever and cervical lymphadenopathy are the most frequent clinical manifestations of HNL in Chinese children, which often coexist with aseptic meningitis. HNL patients with risk factors require follow-up for recurrence.
Shedding light on hidden dynamics: partner controlling behavior and women's alcohol consumption in Ghana
Authors: Okyere Joshua , Salu Samuel , Ayebeng Castro , Dickson Kwamena Sekyi
Published: June 2024

Background

While existing literature suggests a link between alcohol intake and the perpetuation of controlling behaviors, reverse association is yet to be established. Therefore, our study aims to extend the current understanding of the determinants of alcohol consumption among women in Ghana by investigating the association between partner controlling behavior and women’s past month’s alcohol consumption.

Methods

The study relied on data from the 2022 Ghana demographic and health survey. Analysis was based on observations from 5137 women with complete information on partner controlling behavior and past month alcohol consumption. Descriptive statistics, bivariate and multivariate logistic regression were computed. All analyses were executed in STATA version 18.

Results

About 15.05% of women consumed alcohol; 37.31% of the respondents had partners who exhibited controlling behaviors. Women who reported experiencing partner controlling behaviors were 1.19 times more likely to engage in alcohol consumption compared to those who did not report such behaviors (AOR = 1.19; 95% CI 1.01–1.41). Additionally, the study identified other significant predictors of alcohol consumption among women, including experiences of sexual violation (AOR = 1.62; 95% CI 1.21–2.15) and richer wealth (AOR = 0.76; 95% CI 0.59–0.97).

Conclusion

In conclusion, experiencing partner controlling behavior is associated with higher risk of alcohol consumption. Thus, underscoring the importance of addressing not only individual-level factors but also relational dynamics in understanding and addressing alcohol intake among women. Policy makers and program implementers must prioritize interventions aimed at promoting healthy relationship dynamics and addressing gender-based power imbalances. Furthermore, healthcare providers should be trained recognize and address partner controlling behaviors and sexual violence as part of comprehensive interventions for reducing alcohol consumption among women.
Metric multidimensional scaling for large single-cell datasets using neural networks
Authors: Canzar Stefan , Do Van Hoan , Jelić Slobodan , Laue Sören , Matijević Domagoj , Prusina Tomislav
Published: June 2024

Metric multidimensional scaling is one of the classical methods for embedding data into low-dimensional Euclidean space. It creates the low-dimensional embedding by approximately preserving the pairwise distances between the input points. However, current state-of-the-art approaches only scale to a few thousand data points. For larger data sets such as those occurring in single-cell RNA sequencing experiments, the running time becomes prohibitively large and thus alternative methods such as PCA are widely used instead. Here, we propose a simple neural network-based approach for solving the metric multidimensional scaling problem that is orders of magnitude faster than previous state-of-the-art approaches, and hence scales to data sets with up to a few million cells. At the same time, it provides a non-linear mapping between high- and low-dimensional space that can place previously unseen cells in the same embedding.
Zedoary turmeric oil injection ameliorates lung inflammation via platelet factor 4 and regulates gut microbiota disorder in respiratory syncytial virus-infected young mice
Authors: Wu Yu-Zhuo , Zhang Qian , Li Hua , Jiang Cheng-Xi , Li Xiao-Kun , Shang Hong-Cai , Lin Sheng
Published: June 2024

Background

Respiratory syncytial virus (RSV)-induced lung inflammation is one of the main causes of hospitalization and easily causes disruption of intestinal homeostasis in infants, thereby resulting in a negative impact on their development. However, the current clinical drugs are not satisfactory. Zedoary turmeric oil injection (ZTOI), a patented traditional Chinese medicine (TCM), has been used for clinical management of inflammatory diseases. However, its in vivo efficacy against RSV-induced lung inflammation and the underlying mechanism remain unclear.

Purpose

The present study was designed to confirm the in vivo efficacy of ZTOI against lung inflammation and intestinal disorders in RSV-infected young mice and to explore the potential mechanism.

Study design and methods

Lung inflammation was induced by RSV, and cytokine antibody arrays were used to clarify the effectiveness of ZTOI in RSV pneumonia. Subsequently, key therapeutic targets of ZTOI against RSV pneumonia were identified through multi-factor detection and further confirmed. The potential therapeutic material basis of ZTOI in target tissues was determined by non-target mass spectrometry. After confirming that the pharmacological substances of ZTOI can reach the intestine, we used 16S rRNA-sequencing technology to study the effect of ZTOI on the intestinal bacteria.

Results

In the RSV-induced mouse lung inflammation model, ZTOI significantly reduced the levels of serum myeloperoxidase, serum amyloid A, C-reactive protein, and thymic stromal lymphoprotein; inhibited the mRNA expression of IL-10 and IL-6; and decreased pathological changes in the lungs. Immunofluorescence and qPCR experiments showed that ZTOI reduced RSV load in the lungs. According to cytokine antibody arrays, platelet factor 4 (PF4), a weak chemotactic factor mainly synthesized by megakaryocytes, showed a concentration-dependent change in lung tissues affected by ZTOI, which could be the key target for ZTOI to exert anti-inflammatory effects. Additionally, sesquiterpenes were enriched in the lungs and intestines, thereby exerting anti-inflammatory and regulatory effects on gut microbiota.

Conclusion

ZTOI can protect from lung inflammation via PF4 and regulate gut microbiota disorder in RSV-infected young mice by sesquiterpenes, which provides reference for its clinical application in RSV-induced lung diseases.
Single molecule array measures of LRRK2 kinase activity in serum link Parkinson’s disease severity to peripheral inflammation
Authors: Yuan Yuan , Li Huizhong , Sreeram Kashyap , Malankhanova Tuyana , Boddu Ravindra , Strader Samuel , Chang Allison , Bryant Nicole , Yacoubian Talene A. , Standaert David G. , Erb Madalynn , Moore Darren J. , Sanders Laurie H. , Lutz Michael W. , Velmeshev Dmitry , West Andrew B.
Published: June 2024

Background

LRRK2-targeting therapeutics that inhibit LRRK2 kinase activity have advanced to clinical trials in idiopathic Parkinson’s disease (iPD). LRRK2 phosphorylates Rab10 on endolysosomes in phagocytic cells to promote some types of immunological responses. The identification of factors that regulate LRRK2-mediated Rab10 phosphorylation in iPD, and whether phosphorylated-Rab10 levels change in different disease states, or with disease progression, may provide insights into the role of Rab10 phosphorylation in iPD and help guide therapeutic strategies targeting this pathway.

Methods

Capitalizing on past work demonstrating LRRK2 and phosphorylated-Rab10 interact on vesicles that can shed into biofluids, we developed and validated a high-throughput single-molecule array assay to measure extracellular pT73-Rab10. Ratios of pT73-Rab10 to total Rab10 measured in biobanked serum samples were compared between informative groups of transgenic mice, rats, and a deeply phenotyped cohort of iPD cases and controls. Multivariable and weighted correlation network analyses were used to identify genetic, transcriptomic, clinical, and demographic variables that predict the extracellular pT73-Rab10 to total Rab10 ratio.

Results

pT73-Rab10 is absent in serum from Lrrk2 knockout mice but elevated by LRRK2 and VPS35 mutations, as well as SNCA expression. Bone-marrow transplantation experiments in mice show that serum pT73-Rab10 levels derive primarily from circulating immune cells. The extracellular ratio of pT73-Rab10 to total Rab10 is dynamic, increasing with inflammation and rapidly decreasing with LRRK2 kinase inhibition. The ratio of pT73-Rab10 to total Rab10 is elevated in iPD patients with greater motor dysfunction, irrespective of disease duration, age, sex, or the usage of PD-related or anti-inflammatory medications. pT73-Rab10 to total Rab10 ratios are associated with neutrophil degranulation, antigenic responses, and suppressed platelet activation.

Conclusions

The extracellular serum ratio of pT73-Rab10 to total Rab10 is a novel pharmacodynamic biomarker for LRRK2-linked innate immune activation associated with disease severity in iPD. We propose that those iPD patients with higher serum pT73-Rab10 levels may benefit from LRRK2-targeting therapeutics that mitigate associated deleterious immunological responses.
Deciphering the performance of macrophages in tumour microenvironment: a call for precision immunotherapy
Authors: Toledo Belén , Zhu Chen Linrui , Paniagua-Sancho María , Marchal Juan Antonio , Perán Macarena , Giovannetti Elisa
Published: June 2024

Macrophages infiltrating tumour tissues or residing in the microenvironment of solid tumours are known as tumour-associated macrophages (TAMs). These specialized immune cells play crucial roles in tumour growth, angiogenesis, immune regulation, metastasis, and chemoresistance. TAMs encompass various subpopulations, primarily classified into M1 and M2 subtypes based on their differentiation and activities. M1 macrophages, characterized by a pro-inflammatory phenotype, exert anti-tumoural effects, while M2 macrophages, with an anti-inflammatory phenotype, function as protumoural regulators. These highly versatile cells respond to stimuli from tumour cells and other constituents within the tumour microenvironment (TME), such as growth factors, cytokines, chemokines, and enzymes. These stimuli induce their polarization towards one phenotype or another, leading to complex interactions with TME components and influencing both pro-tumour and anti-tumour processes.

This review comprehensively and deeply covers the literature on macrophages, their origin and function as well as the intricate interplay between macrophages and the TME, influencing the dual nature of TAMs in promoting both pro- and anti-tumour processes. Moreover, the review delves into the primary pathways implicated in macrophage polarization, examining the diverse stimuli that regulate this process. These stimuli play a crucial role in shaping the phenotype and functions of macrophages. In addition, the advantages and limitations of current macrophage based clinical interventions are reviewed, including enhancing TAM phagocytosis, inducing TAM exhaustion, inhibiting TAM recruitment, and polarizing TAMs towards an M1-like phenotype. In conclusion, while the treatment strategies targeting macrophages in precision medicine show promise, overcoming several obstacles is still necessary to achieve an accessible and efficient immunotherapy.