bluuebunny/crossref_metadata_2025 huggingface dataset:
Whether medicine supply is really meeting primary health care needs—a mixed-methods study in Shandong Province, China
Authors: Fan ZhinXin , Gao TianTian , Sun Qiang , Babar Zaheer-Ud-Din Babar
Published: March 2024

Background
With the ageing population, the increasing prevalence of chronic non-communicable diseases, and the diversified needs for primary health care (PHC) medicines, it is necessary to rethink the functional role of the supply of PHC medicines. This study aims to comprehensively evaluate the supply of PHC medicines and the status of meeting PHC medicine needs.
Methods
We did a mixed-methods study to evaluate the supply of PHC medicines in Shandong Province. In the qualitative study, semi-structured interviews were conducted with the pharmacy managers, physicians, and patients in county hospitals, township hospitals, and village clinics; in the quantitative study, survey questionnaires were distributed to county hospitals, township hospitals, and patients, and a prescription review was performed in township hospitals. A senior pharmacist from a tertiary hospital accompanied us on a visit to inspect the PHC pharmacies. These quantitative assessments were triangulated with qualitative pharmacy managers, physicians, and patients and discussions.
Results
The supply of PHC medicines based on the existing medicines list was relatively good, and shortages occurred sporadically and locally, resulting a minor impact on clinical medication. 211 county hospitals and 1,581 township hospitals participated in the survey, revealing an average annual frequency of medicine shortages of 8.6 times for county hospitals and 5.7 times for township hospitals. Nonetheless, off-list medicines were in short supply, failing to meet patients’ need as determined by health outcome. Of the 6,323 patient medication surveys, 945 (14.9%) indicated medicine shortages, with half of these attributable to organizations lacking required medicines. On average, the prescription qualified rate of 37 township hospitals was 72.2%. The study revealed the need to optimize the list of PHC medicines and strengthen the capacity of healthcare services.
Conclusions
The discrepancy between patients’ need for PHC medicine and present medicine supply is noteworthy. The supply of PHC medicines should shift its focus from providing medicines based solely on an existing list to prioritizing health outcomes to adequately meet patient medicine needs. Integrated health care may be a novel strategy to establish unified medicines lists and achieve uniform pharmaceutical services in PHC.
Multi-Scalar Data Integration Decoding Risk Genes for Chronic Kidney Disease
Authors: Ding Shiqi , Guo Jing , Chen Huimei , Petretto Enrico
Published: March 2024

Background: Chronic Kidney Disease (CKD) impacts over 10% of the global population and recently advancements in high-throughput analytical technologies are uncovering the complex physiology underlying this condition. Through the integration of Genome-Wide Association Studies (GWAS), RNA sequencing (RNA-seq), and single-cell RNA sequencing (scRNA-seq) summary statistics, our study aimed to explore the genes and cell types relevant to CKD traits.
Methods: The GWAS Catalog and the UK Biobank (UKB) database provided GWAS summary data for the end stage of renal failure (ESRD) and decreased eGFR (CKD) with or without diabetes and (micro)proteinuria. Gene Expression Omnibus (GEO) transcriptome datasets were utilized to establish glomerular and tubular gene expression between CKD patients and healthy individuals. The expression of key genes at the single-cell level were obtained from the ScRNA-seq dataset available on Zenodo. The differentially expressed genes (DEGs), crosstalk co-expression networks, and enrichment analysis were further conducted for these CKD risk genes.
Results: A total of 779 distinct SNPs were identified from GWAS across different traits of CKDs, which were involved in 681 genes. Majority of these risk genes are identical referring in certain CKD trait, but share the common pathways, including extracellular matrix (ECM), circadian entrainment, and energy metabolism. The ECM modelling was also enriched in upregulated glomerular and tubular DEGs from CKD kidneys compared to healthy controls and the expression of relevant collagen genes, COL8A1, COL6A3, and COL1A2, are prevalent in fibroblasts/myofibroblasts. Meanwhile, physiological functions of kidney, including circadian entrainment, were downregulated in CKD kidneys. LUC7L3 was downregulated in CKD and enriched in podocytes. We also highlighted the regulated risk genes of CKD mainly expressed in tubular cells and immune cells in the kidney.
Conclusions: Our integrated analysis highlight the genes, pathways, and relevant cell types associational with the pathogenesis of kidney traits, as a basis for further mechanistic studies to understand the pathogenesis of CKD.
Integrating CBCL with Seminar Teaching Method in Normal Human Anatomy Education for Nursing Students
Authors: WU Xueping , Lv Yehui , Yang Ling , YANG Zhifang
Published: March 2024

Purpose:
The aim of this study is to explore the effectiveness of integrating CBCL (Case Based Collaborative Learning) and seminar teaching approach into general human anatomy courses, with the aim of providing students with an educational experience that reflects clinical practice.
Method:
Utilizing a prospective cohort study design, 61 nursing students from the 2021 cohort were assigned as the control group, while 60 nursing students from the 2022 cohort comprised the experimental group. The control group received traditional teaching methods, whereas the experimental group was taught using CBCL in conjunction with Seminar teaching mode. The effectiveness of the two teaching approaches was evaluated by comparing differences in examination scores, teaching satisfaction, teamwork skills, critical thinking abilities, and other aspects between the two groups of students.
Results:
The experimental group demonstrated significantly higher overall scores compared to the control group (P < 0.05). The questionnaire survey revealed that the experimental group expressed higher satisfaction with the teaching methods, problem-solving abilities, learning capabilities, and team collaboration enhancement than the control group, with statistically significant differences (P < 0.05). No significant differences were found between the two groups in the scores from two Chinese versions of the Critical Thinking Ability Scale (P > 0.05). Following the course, the experimental group exhibited higher CTDI-CV scores in seeking truth, open thinking, analytical skills, systematic thinking, self-confidence, thirst for knowledge, and cognitive maturity compared to the control group, with statistically significant differences (all P < 0.01).
Conclusion:
The integration of CBCL teaching method and Seminar represents an innovative teaching model within the normal human anatomy teaching process. This model blends the practicality of CBCL with the interactivity of Seminar, leading to improved student overall grades, teaching satisfaction, and critical thinking abilities.
Prevalence and effects of Vitamin D receptor polymorphism on bone mineral density and metabolism in patients with systemic sclerosis: a preliminary study
Authors: Schulz Nils , Dischereit Gabriel , Henke Laura , Lange Uwe , Klemm Philipp
Published: March 2024

Introduction: Patients with systemic sclerosis (SSc) have a disproportionately high prevalence of reduced bone mineral density (BMD). Polymorphisms of the vitamin D receptor (VDR) gene have been associated with osteoporosis in patients with autoimmune diseases. The aim of this study was to investigate the prevalence and possible effects of VDR polymorphism on BMD and bone metabolism in patients with SSc. Methods: In patients with SSc measurement of BMD was performed using dual-energy X-ray absorptiometry. VDR polymorphisms (FokI, BsmI) were genotyped using restriction fragment length polymorphism analysis. Markers of bone metabolism (calcium, osteocalcin, β-crosslaps) were determined. Primary endpoint was the prevalence of VDR gene polymorphisms and the association with reduced BMD. Secondary endpoints included associations between bone metabolism and VDR gene polymorphism. Results: 79 caucasian patients with SSc were included. Overall, 83.5% had reduced BMD (51.9% osteopenia, 31.6% osteoporosis). The prevalence of VDR gene polymorphism (73% Bsml, 77% Fokl) was comparable to studies in healthy and rheumatic populations. The homozygous presence of FokI polymorphism, but not BsmI, was significantly associated with reduced axial BMD. Fokl polymorphism was significantly associated with reduced CTX levels, although changes remained within the reference limits. Conclusion: VDR polymorphisms can frequently be found in patients with SSc in comparable prevalence to healthy and rheumatic populations. The homozygous presence of FokI polymorphism, but not BsmI, was significantly associated with reduced axial BMD. This could be a possible contributor for the high prevalence of reduced BMD in 83.5% of patients with SSc in this study. Trial registration number: DRKS00032768, date: 05.10.2023, retrospectively registered
Genetic Association Analysis Between Depression and Gastroesophageal Reflux Disease- Related Phenotypes
Authors: Xu Ting-Ting , Geng Lin , Zhang Xiu-lian , Chang Cen , Zhu Sheng-Liang , Wang Yi , Fang Sheng-Quan , Li Li
Published: March 2024

Objective
A plethora of studies have illuminated the significant association between depression and Gastroesophageal Reflux Disease (GERD), especially refractory gastroesophageal reflux disease (rGERD), yet the causal interplay and directionality of this relationship remain largely unexplored. This study aims to shed light on the bidirectional causative connections and the potential genetic mechanisms underlying the relationship between depression and GERD, as well as its subtypes.
Methods
Utilizing comprehensive summary data from Genome-Wide Association Studies (GWAS) pertaining to depression, GERD, Reflux Esophagitis (RE), and Non-Erosive Reflux Disease (NERD), this study implemented Mendelian Randomization to discern the independent causal relationships between depression and these gastroesophageal disorders. We employed an integrative approach, amalgamating data from GWAS, Expression Quantitative Trait Loci (eQTL), and other multi-omics analyses. Techniques such as SMR and FUMA were applied to identify potential pathogenic genes implicated in depression and the subtypes of GERD. Enrichment analyses were conducted to elucidate the potential biological pathways through which depression modulates GERD and its variants.
Results
The study revealed that depression significantly increases the risk of developing GERD and NERD, but not RE. No causal link was identified between GERD, RE, NERD, and depression. In-depth analysis through SMR and FUMA pinpointed GMPPB as a potential susceptibility gene for depression, manifesting across the brain, spinal cord, and peripheral blood. For GERD, the identified susceptibility genes present in the gastroesophageal junction, esophageal mucosal and muscular layers, and peripheral blood included RP4-717I23.3, RAB7L1, BROX, TAF1B, RP11-95D17.1. For NERD, potential susceptibility genes localized in similar tissues comprised GBP3, METTL18, SERPINC1, ZNF496, AC016683.6, PAX8GLS, LARS2, NCKIPSD, QRICH1, AMT. The genetic loci linked to both depression and GERD predominantly cluster in areas such as the T cell receptor signaling pathway, DNA binding transcription factor activity, sequence-specific DNA binding, Rickman tumor differentiated well vs moderately DN, etc. Genetic loci associated with depression and NERD are mainly concentrated in areas of Nucleosome organization, Protein and complex subunit organization, and, similarly, the T cell receptor signaling, etc.
Conclusion
The findings of this study indicate that depression contributes to an increased incidence of GERD and NERD. The potential mechanisms underpinning this association might involve the brain-gut axis, encompassing neuroimmune pathways, DNA and RNA transcriptional regulation, and protein metabolism processes.
Rethinking CF organization of care in the era of highly effective modulator: a nationwide research program HORIZON
Authors: Haesaebert Julie , Reynaud Quitterie , Durieu Isabelle , Poupon-Bourdy Stephanie , Nouvel Thierry , Reix Philippe
Published: March 2024

Highly effective modulator therapy (HEMT) is now available to a wider range of people with cystic fibrosis (pwCF). It has significantly improved short-term clinical outcomes and has the potential to alter the natural history of this fatal genetic disease. If long-term follow-up observational data is required to ensure clinical benefits, it is obvious that it will also change the needs of pwCF and the roles and missions of healthcare professionals (HCPs) in CF centers and beyond. We will conduct a nationwide research program called 'HORIZON' to support the necessary changes in the organization of CF care in the coming years. Our primary objective is to design a new model of CF care organization that can respond to the new needs and missions of pwCF and HCPs in this era of rapid and profound changes due to HEMT. This research program is based on the intervention mapping method, in which we will conduct the first four steps to design and plan the implementation of a new organization of care. The program will involve all stakeholders of the CF care network, including HCPs from CF care centers and outside, pwCF and their families, patient organizations, and experts from other countries. It will combine quantitative and qualitative research approaches and rely on an 'action research' method. Anticipating and supporting the reorganization of CF care in France requires a robust research program to find the best model that meets the expectations of all key stakeholders.
Pre-pregnancy intrauterine device use is associated with a reduced risk of subsequent preterm birth: a large population-based cohort study
Authors: Chen Xing , Wang Tao , Zhang Yan , Xie Zhengyuan , Kong Cai , Wu Binxue , Lan Yuzhi , Zhao Zigao , Song Xiangjing , Ye Hanfeng , Che Yan
Published: March 2024

Background
The effect of pre-pregnancy intrauterine device (IUD) use on subsequent preterm birth (PTB) remains unclear. To investigate the association between IUD use before pregnancy and subsequent PTB.
Methods
A total of 242,009 women who participated in the National Free Preconception Health Examination Project (NFPHEP) in Yunnan from 2013 to 2019 were included in the study. All study participants were classified into three groups according to their use of pre-pregnancy contraceptive methods: non-method users, IUD users, and other method users. We used multivariable Poisson regression model to investigate the association between the use of an IUD before pregnancy and subsequent PTB. Further models analyzed the multiplicative and additive interactions between pre-pregnancy IUD use and county deprivation.
Results
Of all the participants, 45,772 (18.9%) used IUDs before pregnancy, 39,627 (16.4%) used other contraceptive methods, and 156,506 (64.7%) were non-method users. The overall PTB rate was 4.8% (95% confidence interval [95% CI], 4.7–4.9%), and women in the IUD group had a significantly lower PTB rate (4.3%, 95% CI 4.1–4.5%) than women in the non-method users (4.9%, 95% CI 4.8–5.1%) and other method groups (4.7%, 95% CI 4.5–4.9%). IUD use before pregnancy was associated with a reduced risk of subsequent PTB (model 1: adjusted relative risk [aRR] 0.84, 95% CI 0.79 to 0.88; model 2: aRR 0.84, 95% CI 0.79 to 0.90). In counties with a normal level of development, IUD users had a 30% lower risk of subsequent PTB than non-users (aRR 0.70, 95% CI 0.63 to 0.77). Compared with non-IUD users from the least developed counties, those from counties with a normal level of socioeconomic development had the lowest risk of subsequent PTB (aRR 0.72, 0.62 to 0.83). The additive interaction between pre-pregnancy IUD use and low level of county development was statistically significant (relative excess risk due to interaction [RERI] -0.27, -0.40 to -0.13).
Conclusion
Pre-pregnancy IUD use is associated with a reduced risk of subsequent PTB. Pre-pregnancy IUD users in counties with a normal level of development were associated with a lower risk of subsequent PTB than their counterparts in the least developed countries.
Thoughtful faces: inferring internal states across species using facial features
Authors: Tlaie Alejandro , Hay Muad Abd El , Mert Berkutay , Taylor Robert , Ferracci Pierre-Antoine , Shapcott Katharine , Glukhova Mina , Pillow Jonathan , Havenith Martha , Schölvinck Marieke
Published: March 2024

Animal behaviour is shaped to a large degree by internal cognitive states, but it is unknown whether these states are similar across species. To address this question, we developed a virtual reality setup in which mice and macaques engage in the same naturalistic visual foraging task. We exploited the richness of a wide range of facial features extracted from video recordings during the task, to train a Markov-Switching Linear Regression (MSLR). By doing so, we identified, on a single-trial basis, a set of internal states that reliably predicted when the animals were going to react to the presented stimuli. Even though the model was trained purely on reaction times, it could also predict task outcome, supporting the behavioural relevance of the inferred states. The identified states were comparable between mice and monkeys. Furthermore, each state corresponded to a characteristic pattern of facial features, highlighting the importance of facial expressions as manifestations of internal cognitive states across species.
Comparison of Surgical Outcomes of da Vinci Surgical Systems X and Xi: A Single-center Study
Authors: Nagata Hiroki , Komatsu Hiroaki , Yamamoto Koji , Okawa Masayo , Hikino Kohei , Iida Yuki , Wada Ikumi , Ikebuchi AI , Sawada Mayumi , Azuma Yukihiro , Sato Shinya , Harada Tasuku , Taniguchi Fuminori
Published: March 2024

Background: The da Vinci surgical systems (X and Xi) are fourth-generation systems marketed by Intuitive Inc. The X system is less expensive compared with the Xi system. This study compared the surgical outcomes of patients who underwent hysterectomy using the X and Xi systems.
Methods: Data of 172 patients who underwent robot-assisted total hysterectomies by four surgeons between April 2019 and March 2023 were retrospectively analyzed in a single-center study. The patients were divided into two groups based on the system used for the surgery. Approval was granted by the Institutional Review Board of the Tottori University Hospital (22A134). All patients provided opt-out consent in accordance with institutional guidelines.
Results: The operative and console times in group X were shorter than those in group Xi after propensity score matching for age, body mass index, nulliparity, previous history of abdominal or pelvic surgery, pre-operative diagnosis, and surgical approach. No statistical differences were observed in a subgroup analysis of patients who underwent robot-assisted total laparoscopic hysterectomy without lymphadenectomy.
Conclusion: Perioperative outcomes for the X and Xi da Vinci surgical systems were equivalent. The cost-effective X system may allow the widespread use of robotic surgeries.
Individual Placement and Support; Service Development and Implementation of an Evidence-based Practice in Iran
Authors: Mirsepassi Zahra , Tabatabaee Maryam , Panahi Mansoureh , Chehrenegar Shahrzad , Sharifi Vandad , Shekari Pardis , Ghelichi Elnaz Pashaei , Nooshabadi Zohreh Tadbiri , Rasoulian Maryam
Published: March 2024

Background
Individuals with severe mental illness (SMI) often face challenges in obtaining and maintaining employment, resulting in low occupational rates. The Individual Placement and Support (IPS) program has been proven effective in promoting employment for people with SMI. However, its implementation in low-resource settings is limited. This study aims to share the experience of developing and implementing IPS in Iran and discuss the encountered challenges.
Methods
An interdisciplinary team was formed, including academic members and experts in providing occupational services. Employment specialists were trained through workshops and supervision sessions. Stakeholders, including hospital administrators and psychiatrists, were engaged to promote the adoption of IPS. The study included individuals with SMI who accepted the invitation to participate. The IPS fidelity scale was utilized to assess the quality of the service.
Results
During the 36-month study period, 40 clients were referred, with a majority being male and having a diploma or university degree. The IPS fidelity scale scores indicated good fidelity at 6 months and exemplary fidelity at 12 months. However, a significant dropout rate was observed, with the majority occurring during the first and third steps of the IPS process.
Conclusion
The implementation of IPS in Iran faced challenges, including limited resources and high dropout rates. Despite these challenges, the study demonstrates the feasibility of developing and implementing IPS in a low-resource setting. Efforts to secure funding and engage stakeholders were crucial for the sustainability of the service. This study highlights the need for comprehensive evidence-based occupational programs for individuals with SMI in Iran and similar settings. Further research and interventions are warranted to address the identified challenges and improve employment outcomes for individuals with SMI.
Association of triglyceride-glucose index and its related parameters with atherosclerotic cardiovascular disease: evidence from a 15-year follow-up of Kailuan cohort
Authors: Xia Xue , Chen Shuohua , Tian Xue , Xu Qin , Zhang Yijun , Zhang Xiaoli , Li Jing , Wu Shouling , Wang Anxin
Published: March 2024

Background Triglyceride glucose (TyG) index and its related parameters has been introduced as cost-effective surrogate indicators of insulin resistance, while prospective evidence on their effects on risk of atherosclerotic cardiovascular disease (ASCVD) remained scattered and inconsistent. We aimed to evaluate the association of TyG with new-onset ASCVD and further compare their predictive capacity.
Method A total of 95,342 ASCVD-free participants were enrolled from the Kailuan study. TyG and its related parameters were defined by fasting blood glucose, triglyceride, BMI, WC and WHtR. The primary outcome was incident ASCVD, comprising myocardial infarction (MI) and ischemic stroke (IS). Cox proportional hazard models and restricted cubic spline analyses were adopted to investigate the association between each index and ASCVD. The C-index, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were used for comparison of their predictive value for ASCVD.
Results During a median follow-up of 15.0 years, 8,031 new cases of ASCVD were identified. The incidence rate of ASCVD increased along with elevated levels of each index, and the relationships were found to be nonlinear in the RCS analyses. The hazard ratio (HR) and 95% confidence interval (95% CI) for ASCVD was 1.39 (1.35, 1.43), 1.46 (1.41, 1.50), 1.50 (1.46, 1.55), and 1.52 (1.48, 1.57) per 1 IQR increase of baseline TyG, TyG-BMI, TyG-WC, and TyG-WHtR, respectively, and the association were more pronounced for females and younger individuals aged <60 years (P for interaction<0.05). Using the updated mean or time-varying measurements instead of baseline indicators did not significantly alter the primary findings. Additionally, TyG-WC and TyG-WHtR showed better performance in predicting risk of ASCVD than TyG, with the IDI (95% CI) of (0.001, 0.004) and 0.004 (0.001, 0.004) and the category-free NRI (95% CI) of 0.120 (0.025, 0.138) and 0.143 (0.032, 0.166), respectively. Similar findings were observed for MI and IS.
Conclusions Both the TyG index and its related parameters were significantly and positively associated with ASCVD. TyG-WC and TyG-WHtR had better performance in predicting incident ASCVD than TyG, which might be more suitable indices for risk stratification and enhance the primary prevention of ASCVD.
Comparing Neuroendocrine Recovery Between Surgical and Conservative Management in Pituitary Apoplexy Patients: A Propensity Score-Matched Analysis
Authors: Saktiwarawat Krittithee , Tunthanathip Thara , Oearsakul Thakul , Taweesomboonyat Chin
Published: March 2024

Background: Pituitary apoplexy is a rare and potentially life-threatening clinical syndrome. Patients may present with severe neuro-ophthalmologic or endocrine symptoms. Current evidence is unclear whether conservative or surgical management leads to the best neuroendocrine outcomes. This study aimed to compare neuroendocrine outcomes between surgical and conservative treatments in a single center.
Methods: Cases of patients with pituitary apoplexy who received transsphenoidal surgery or conservative management in Songklanagarind Hospital between January 1, 2005 and December 31, 2022 were retrospectively reviewed. A propensity score matching method was used to adjust bias from treatment selection (surgery or conservative treatment). Differences in visual acuity, visual field, cranial nerve, and endocrine outcomes between the surgical and conservative treatment groups were analyzed using logistic regression analysis.
Results: This study included 127 patients, with 98 and 29 patients in the surgical and the conservative treatment group, respectively. The optimal matching method was used for propensity score matching. Compared to the conservative group, the surgically treated patients had a significantly higher rate of visual field recovery (odds ratio (OR): 12.89, P = 0.007). However, there were no statistical differences in the recovery rate of preoperative visual acuity, cranial nerve, and endocrine deficits between the groups.
Conclusions: Transsphenoidal surgery was associated with a higher rate of visual field recovery when compared to the conservative treatment for pituitary apoplexy patients. Careful selection of appropriate treatment based on the patient’s presentation and neuroendocrine status will result in the best outcomes while avoiding unnecessary surgical intervention.
Multi-scenario surveillance of respiratory viruses in aerosols with a sub-single molecule spatial resolution
Authors: Liu Peng , Li Bao , Lin Baobao , Wang Yan , Shi Ye , Zeng Wu , Zhao Yulan , Gu Yin , Gao Hui , Cheng Hao , Zheng Xiaoqun , Xiang Guangxin , Wang Guiqiang
Published: March 2024

Highly sensitive airborne virus monitoring is critical for preventing and containing epidemics. However, the detection of airborne viruses at ultra-low concentrations remains challenging due to the lack of ultra-sensitive methods and easy-to-deployment equipment. Here, we present an integrated microfluidic cartridge that can accurately detect SARS-CoV-2 and various respiratory viruses with a sensitivity of 10 copies/mL. When seamlessly integrated with a high-flow aerosol sampler, our microdevice can achieve a sub-single molecule spatial resolution of 0.83 copies/m3for airborne virus surveillance. We then designed a series of virus-in-aerosols monitoring systems (RIAMs), including versions of a multi-site sampling RIAMs (M-RIAMs), a stationary real-time RIAMs (S-RIAMs), and a roaming real-time RIAMs (R-RIAMs) for different application scenarios. Using M-RIAMs, we performed a comprehensive evaluation of 210 environmental samples from COVID-19 patient wards, including 30 aerosol samples. The highest positive detection rate of aerosol samples (60%) proved the aerosol-based SARS-CoV-2 monitoring represents an effective method for spatial risk assessment. The detection of 78 aerosol samples in real-world settings via S-RIAMs confirmed its reliability for ultra-sensitive and continuous airborne virus monitoring. Therefore, RIAMs shows the potential as an effective solution for mitigating the risk of airborne virus transmission.
Cultivar-specific wheat-associated microbiomes and metabolites in response to nitrogen deficiency
Authors: Chan Lok Hang , Lam Shu Kee , Chen Deli , Tang Caixian , Chen Qinglin , Roessner Ute , Salazar Vinícius Werneck , Gupta Sneha , Dias Daniel Anthony , Hu Hang-Wei
Published: March 2024

Background and Aims

Nitrogen (N) deficiency in soil constrains plant growth, which may potentially be alleviated by beneficial soil microbes. However, there is limited knowledge of the plant-microbe interactions of wheat cultivars with different N-use efficiency (NUE) under N deficiency.

Methods

We investigated the responses of soil and root endosphere microorganisms as well as root metabolites of two wheat cultivars (cv. Mace and Gladius) with reported high and low NUE, respectively, using a glasshouse experiment and a hydroponic experiment with three N levels.

Results

The rhizosphere bacterial community of Mace shifted under N deficiency, but not in its root endosphere. Conversely, the rhizosphere bacterial community of Gladius remained unchanged under N deficiency but shifted in its root endosphere. The metagenomic analysis illustrated that bacterial growth and motility in the rhizosphere of Mace, but not of Gladius, were potentially enhanced under N deficiency. A 4-fold increase in octadecanoic acid in the root extract of Mace, but not Gladius, under N deficiency, suggesting the potential role of octadecanoic acid in shaping the rhizobacterial community in Mace with higher reported NUE.

Conclusion

Our study provides new evidence highlighting the divergent responses of wheat-associated microorganisms and root metabolites to N deficiency in the two cultivars. In addition to this, our findings suggest that wheat cultivars with higher NUE may selectively recruit beneficial bacterial communities through secreting specific metabolites, thereby enhancing their growth under N-limited conditions.
Quantitative evaluation of the efficacy and safety profiles of two types of targeted inhibitors combined with endocrine therapy in ER+/HER2- metastatic breast cancer
Authors: Pan Meiyu , Lin Yan , Liu Yinhui , Xu Ruijuan , Yang Jin
Published: March 2024

Purpose
The aim of this study was to quantitatively compare the efficacy and safety of CDK4/6 inhibitors and PI3K/AKT/mTOR inhibitors for ER+/HER2- metastatic breast cancer.
Methods
A parametric survival function was used to analyze the time course of overall survival (OS) and progression-free survival (PFS). The objective response rate (ORR) and the incidence of any grade and grade 3–4 adverse events were summarized using the random-effects model of a single-arm meta-analysis.
Results
This study included 44 arms from 48 publications, with a total sample size of 7,881 patients. Our study revealed that CDK4/6 inhibitors had a median OS of 40.7 months, a median PFS of 14.8 months, and ORR of 40%. Whereas, PI3K/AKT/mTOR inhibitors had a median OS of 29.8 months, a median PFS of 8.3 months, and ORR of 20%. Additionally, this study also found that the proportion of patients with visceral metastases and specific endocrine therapy used in combination significantly impact OS and PFS. In terms of adverse events, CDK4/6 inhibitors exhibited a relatively high incidence of hematological adverse events.
Conclusion
Our study provides solid quantitative evidence for the first-line recommendation of CDK4/6 inhibitors combined with endocrine therapy for ER+/HER2- metastatic breast cancer in clinical guidelines.
Effect of Primary PCI in asymptomatic STEMI patients presenting 12-48 hours of symptom onset, on myocardial viability assessed on SPECT - ‘EPITOME-99’
Authors: Pandit Manjunath Suresh , Sahoo Sibasis , Patel Vishalkumar M , Thangasami Senthilraj , Kashyap Vinayak H , Jameria Jevin , Pandey Vimlesh , Shanishwara Parth
Published: March 2024

Background: Guidelines on revascularization of asymptomatic STEMI patients presenting 12-48 hours of symptom onset are limited, evidence contributing lack of symptoms to non-viable myocardium are scarce. We utilized TC-99mSestaMIBI scan to study the impact of primary PCI on myocardial viability by deriving myocardial salvage index (MSI) in asymptomatic STEMI patients presenting between 12-48 hours of symptom onset to PCI.
Methods and results: We enrolled 141 patients with STEMI (12-48 hours), from January 2020 to December 2023, who then underwent TC-99mSestaMIBI scan, followed by revascularization of IRA with 138 patients completing the designed study with follow-up scan at 3 months. A substantial MSI of > 0.50 was achieved by 36 %, 8% and 5 % of patients from cohort A(12-24 hrs.), B(25-36 hrs.), and C(37-48 hrs.) respectively.Post Hoc analysis determined a comparable AAR of 34.47 %( ±11.70) throughout cohorts, however a greater reduction in FIS [Q=4.72 (p=.00309)]and MSI gain was noted among patients of cohort A alone [Q=4.18 (p=.01025)]. Regression analysis of MSI against PCI timing was negatively correlated (R= -0.41).
Conclusion: Asymptomatic stable STEMI patients presenting 12-24 hours of symptom onset to PCI, benefited from primary PCI with lesser final infarct size and larger MSI. Despite a comparable AAR across cohorts, MSI fell sharply among patients undergoing primary PCI 24-48 hours of symptom onset with a larger final infarct size, warranting viability guided revascularization. Although primary PCI improved final LVEF and MSI in patients with ischemic heart failure, parameter gain alone was insufficient in endeavoring a positive clinical impact.
High temperature and abrasion resistance of fly ash and ceramic waste powder based geopolymer mortar
Authors: Bhavsar Jay , Panchal Vijay Ramanlal
Published: March 2024

The increasing popularity of geopolymer concrete is attributed to its small ecological footprint. Moreover, it presents substantial prospects for employing industrial waste as a substitute binder for producing geopolymer concrete. The ceramic waste powder (CWP), which is a by-product of the ceramic polishing and glazing process, was employed in the manufacturing of geopolymer mortar. This study investigated the heat and abrasion resistance of geopolymer mortar (GM) produced using two different types of CWP and fly ash. A GM was prepared by combining fly ash, CWP, and the alkaline activators NaOH and Na2SiO3. The study examined three different curing conditions: ambient, curing at 60 °C for 24 hours, and curing at 60 °C for 48 hours. All mortar mixes were heated to temperatures of 500°C and 1000°C for a period of 2 hours (h) to study their heat resistance. Both weight loss and compressive strength (CS) were assessed before and after temperature exposure. The assessment of abrasion resistance was conducted in line with the Indian standard. The study suggests that the utilization of CWP enhances the high temperature and abrasion resistance of GM.
Accuracy of Dental Symptom Checker Web Application in the Singapore Military Population
Authors: LIM Songping Nicholas , WOON Xuan Ru , GOH Enhui Charlene , NG Jingwen Claudia , ANG Seng Yao , LIM Teong Joe , ALLEN Patrick Finbarr
Published: March 2024

PurposeThe aim of this study was to investigate the triage performance, clinical efficacy and user perceived utility of a prototype dental SC,Toothbuddy, in assessing unscheduled dental visits in Singapore.MethodsA 5-month pilot trial was conducted for all unscheduled dental attendees to military dental facilities in Singapore between January to May 2023. The accuracy ofToothbuddyto tele-triage the dental conditions into three categories (Routine, Urgent, and Emergency) was determined. Based on the patient-reported symptoms input intoToothbuddy, clinical recommendations were provided for the categories Routine, Urgent and Emergency in the form of advice. Thereafter, all dental attendees were clinically assessed to determine the definitive category. Finally, a user questionnaire asked about the application’s functionality, utility, and user’s satisfaction. Sensitivity and specificity analyses were undertaken.ResultsDuring the period of study, there were 588 unscheduled dental visits who presented with clinical concerns without any prior appointments. Out of these cases, 275 (46.8%) were evaluated to be routine dental conditions where treatment can be delayed or self-managed, 243 (41.3%) required urgent dental care and 60 (10.2%) required emergency dental intervention. The accuracy ofToothbuddysymptom checker in categorizing the correct intervention was 79.6% (468 out of 588 cases). The sensitivity and specificity in categorizing routine vs non-routine conditions was 94.5% (95% CI: 92.0-97.1) and 74.0% (95% CI: 68.8-79.2). The app was generally well-received and rated highly across its user interface, content, and user sentiments.ConclusionPreliminary data suggest thatToothbuddycan perform accurate dental self-assessment for a suitable range of common dental concerns as a promising platform for virtual dental advice on spontaneous dental issues. External validation, further user-enhancements and features are recommended to expandToothbuddyfor wider public use.
Decompressive Craniotomy in Split-Technique (DCST) for TBI in infants: Introducing a new surgical technique to prevent long-term complications
Authors: Sarikaya-Seiwert Sevgi , Shabo Ehab , Schievelkamp Arndt-Hendrik , Born Mark , Wispel Christian , Haberl Hannes
Published: March 2024

Decompressive craniectomy (DC) is rarely required in infants. These youngest patients are vulnerable to blood loss and cranial reconstruction can be challenging due to skull growth and bone flap resorption. On the other hand, infants have thin and flexible bone and osteogenic potential. We propose a new technique called DCST, which makes use of these unique aspects by achieving decompression using the circumstance of the thin and flexible bone. We describe the surgical technique and the follow up course over a period of 13 months. In our series, DCST achieved an adequate decompression and redundantized further surgeries in accordance with decompressive craniectomy.
Analytical performance and visual evaluation of test strips for fentanyl.
Authors: Wu Alan H.B. , Ong Chui Mei , Alamillo Melissa , Farias Steven , Barbosa Luana
Published: March 2024

Background
Testing street drugs for the presence of active drugs and drugs used as adulterants such as fentanyl can provide the user some confidence as to the safety of their pills. As such, disposable testing strips have become available through multiple vendors as a tool set to combat adulterants. Because there is not currently an industry standard for these products, they can vary in specifications and quality. This study serves as a broad evaluation survey across multiple vendors to compare performance and assess the best product for harm reduction.
Methods
We obtained 6 different commercially available different commercially available fentanyl test strips and evaluated them for analytical sensitivity using drug standards. The specificity of the fentanyl strips against fentanyl analogues was also assessed. Powdered fentanyl standards and analogues were initally dissolved in methanol and then serially diluted in water to bracket the manufacturer’s stated test strip sensitivity. Each dilution was tested in duplicate until a negative result was obtained. The ability to discern positive from negative results under different lighting conditions by two observers in duplicate, was also assessed for these strips including different lots for some.
Results
Three of the fentanyl strips had the best sensitivity (at 3.6 ng/mL each), well below the stated sensitivity of 10, 20, and 200 ng/mL. The other three were less sensitive (at 7.2, 29 ng/mL). For specificity against fentanyl analogues, all of the strips tested positive for all of the analogues tested, but at different levels. The visual endpoints for all of the strips were acceptable under normal lighting conditions, but cannot be read when the ambient light is low. The readability at different dwell times are noted.
Conclusion
Based on these results, we determined that the WPHM and Hangzhou SingClean fentanyl test strips had the best analytical sensitivity (3.6 ng/mL). The Henso strip had lower sensitivity but the best discrimination between positive and negative signals. Each of the fentanyl strips had varying degrees of specificity and visibility towards fentanyl drug analogues.
The safety and efficacy of surgery for foot deformity in patients with Charcot-Marie-Tooth disease: a systematic review and meta-analysis
Authors: Song Haibo , Wu Yuanpeng , Zhang Huifang , Liu Zengling , Ren Yuebing
Published: March 2024

Background
The objective of this study is to conduct a comprehensive meta-analysis to assess the safety and effectiveness of surgical treatment in patients with Charcot–Marie–Tooth disease (CMT), the most prevalent inherited peripheral neuropathy. The aim is to assess if surgical interventions improve functional scores in CMT patients, filling literature gaps and guiding evidence-based surgical management.
Methods
We conducted a systematic review and meta-analysis, searching articles in PubMed, Embase, the Cochrane Library databases, and Web of Science from their inception to December 10, 2023. Inclusion criteria involved studies reporting primary data, focusing primarily on surgical treatments for CMT foot deformity, having available full text, and reporting outcomes from more than three patients. Non-surgical treatment studies, review articles, basic research, and cadaveric studies were excluded. Outcomes associated with the surgical management of CMT were obtained using random-effects meta-analysis.
Results
From a total of 572 identified and screened studies, 11 studies (1.9%) comprising 322 feet undergoing surgical procedures for CMT were included. Among them, there were 2 prospective observational studies, 8 retrospective cohort studies, and 1 case report. However, while post-operative ankle function scores showed improvement, patient satisfaction and reintervention rates remained unsatisfactory. Notably, three studies reported significant improvements in the range of motion parameters for tibiotalar flexion with the knee in full extension post-operation. Radiographic examination was conducted to evaluate deformity correction and force lines. Furthermore, complications such as early post-op or subsequent operations, delayed wound healing, blisters, and Ward were monitored in all 11 studies.
Conclusion
Surgical management is effective in improving assessment scores, foot and ankle function, and enabling a faster return to work and sports for patients with CMT. However, caution is needed to minimize complications. Further research, including RCT, is necessary to assess detailed outcomes and identify prognostic factors for treatment decision-making in clinical practice.
A Adaptive Service Deployment Algorithm for Cloud-Edge Collaborative system based on Speedup Weights
Authors: Hu Zhichao , Chen Sheng , Rao Huanle , Hong Chenjie , Huang Ouhan , Xu Xiaobin , Jia Gangyong
Published: March 2024

In the contemporary landscape of edge computing, the deployment of services with stringent real-time requirements on edge devices is increasingly prevalent. However, the challenge of designing an effective service deployment strategy that optimally leverages both cloud and edge resources to deliver high-quality services in production environments persists, primarily due to resource constraints in edge devices. To tackle this issue, we introduce an adaptive service deployment algorithm that utilizes speedup weights for cloud-edge collaborative environments(SWD-AD). This algorithm is crafted by comparing task execution times in both cloud and edge settings and integrating Speedup Weights with resource consumption metrics. During task cluster operations, service-specific task processing data is collected, and cumulative Speedup Weights are computed. Based on this metric, a dynamic service adjustment policy is implemented to facilitate service migration between cloud and edge, optimizing resource allocation. Our performance evaluation experiments reveal that this strategy notably reduces the average response time of tasks by 29.38\% and 25.86\% compared to Swarm and kubernetes (K8s) algorithms, respectively.
Study of The Effect Of Graphene Oxide in Flexible and Moldable Bamboo/Brine Sludge & PDMS-Based Composites for Thermal Applications
Authors: Singhwane Anju , Jaiswal Ayushi , Srivast AK , Verma Sarika
Published: March 2024

The present study introduces a novel approach for developing advanced, adaptable, flexible, and moldable composite using bamboo powder derived from bamboo fiber, graphene oxide (GO), and chlor-alkali waste brine sludge embedded with polydimethylsiloxane (PDMS). The process involves the development of a flexible composite utilizing treated bamboo fiber powder with brine sludge, graphene oxide nanoparticles, and PDMS as a polymer matrix. The study developed three sets of Graphene Oxide GO-reinforced flexible Bamboo composite named TGO 100, TGO 300 and TGO 500. The utilization of this flexible, thermally active bamboo composite holds promise as an alternative in various applications. The developed samples were characterized for their morphological, mechanical, water absorption, and thermal conductivity studies. With the increase in the concentration of graphene oxide (TG0 500 composition) the highest tensile strength is reported to be 0.197 Mpa.The thermal conductivity results demonstrate that the developed flexible material exhibits thermal conductivity properties, with the material achieving excellent values of 0.192, 0.196, and 0.203 W/m·K respectively. Consequently, the bamboo-based flexible composite material possesses outstanding thermal conductive qualities and can find diverse applications across a wide range of fields.
Network pharmacology-based investigation and experimental validation of the mechanism of Metformin in the treatment of acute myeloid leukemia
Authors: Liu Shaoyu , Xu mingming , Yang zhuofan , Li yangzi , Wu Depei , Tang Xiaowen
Published: March 2024

Metformin，a widely used anti-diabetic agent, has shown significant anti-cancer properties as reported in in various cancers, including acute myeloid leukemia. However, the detailed mechanisms by which metformin influences acute myeloid leukemia remain unrevealed. Employing a synergistic approach of network pharmacology and experimental validation, this study systematically identifies and analyses potential Metformin targets and AML-related genes. These findings are then cross-referenced with biomedical databases to construct a target-gene network, providing insights into Metformin's pharmacodynamics in AML treatment. Protein-Protein Interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses are utilized. Results show Metformin's effectiveness in inhibiting AML cell proliferation and inducing apoptosis through the AKT/HIF1A/PDK1 signaling pathway. This research provides insights into Metformin's clinical application in AML treatment.
Unsupervised metric learning via K-ISOMAP for high-dimensional data clustering
Authors: Mendes Rodrigo de P. , Chavari Gustavo H. , Levada Alexandre L. M.
Published: March 2024

Clustering does not assume the knowledge of the class labels, defining an unsupervised learning paradigm relevant for many pattern recognition and machine learning problems. One of the limitations of clustering is that most algorithms rely heavily in a distance function used to compute a dissimilarity measure between the samples. The usual choice is the Euclidean distance, which is known to have a poor discriminant power in high-dimensional spaces and also is quite sensitive to the presence of outliers. In this paper, we propose to investigate how unsupervised metric learning via the curvature-based ISOMAP algorithm (K-ISOMAP) can influence the clustering performance by means of quantitative evaluation metrics. The computation of the local curvature in the dimensionality reduction process allows the incorporation of an adaptive and intrinsic distance metric function into clustering, making it more aware of the geometry of the underlying data manifold. Computational experiments with real-world datasets indicate that the use of K-ISOMAP prior to a clustering algorithm may produce superior Rand, Calinski-Harabasz and Fowlkes-Mallows indices, in comparison to raw and regular ISOMAP data, suggesting that learning a suitable metric can be a relevant pre-processing step before clustering.