bluuebunny/crossref_metadata_2025 huggingface dataset:
DOLPHIN: A Mixed-Methods Study of a Parenting App to Nurture the First Two Years of Life in the Indian Context
Authors: Sravanti Lakshmi , Mundkur Nandini
Published: May 2024

Background:

The first two years of life are critical for brain development. Experiences and exposures during this period can have long-term effects on an individual’s health. Therefore, we aim to develop a program for new parents in the Indian context to help them understand their developing infant’s needs and provide the best possible care grounded in traditional practices to ensure healthy developmental outcomes.

Materials and Methods:

The program was developed using the exploratory–confirmatory framework grounded in qualitative methods—(a) collection of empiric evidence base by conducting a thorough literature review, (b) tacit experience, and (c) focus group discussions with relevant stakeholders. Picture-based content (one picture per day for two years) was created, and the program was expert-validated. A web-based application was developed to make it available to parents, and the program was translated into three regional languages to improve its reach. A telephonic user feedback survey was carried out, and descriptive statistics were used to present the findings from the survey.

Results:

DOLPHIN stands for “Developing Opportunities of Learning for Parents to Help Infant Nurture.” Over 600 parents accessed the program. Feedback is positive in the domains of parental satisfaction and user-friendliness.

Discussion:

The program primarily focuses on ensuring appropriate sensorimotor stimulation and meeting the socioemotional needs of the growing infant through the first two years, emphasizing healthy nutrition and hygiene to ensure holistic development. Therefore, its approach is health-promotive and disease-preventive. It incorporates traditional child-rearing practices of India rich in stimulation, promoting secure attachment, and incidental learning: “readiness.”

Conclusion:

The DOLPHIN program demonstrates a promising approach to supporting new parents in nurturing their infants during the critical first two years of life. With positive feedback and a focus on traditional practices and evidence-based content, it holds potential as a health-promotive and preventive intervention for holistic child development in the Indian context.
Book review: John C. B. Webster, Studying History
Authors: Subodh Sanjay
Published: May 2024

John C. B. Webster, Studying History. Delhi: Primus Books, 2019, xiv + 195 pp. ₹120, ISBN: 9789352907748 (Hardback).
Social Media Use and Impact on Voters and Candidates in Kerala
Authors: Balasundaram Ashok , Sreedharan N.V. , Babu D. Dinesh , Gopinath Prateesh P.
Published: May 2024

This article presents a comprehensive survey of social media usage among Kerala voters across three parliamentary constituencies ( N = 1500). It explores the socio-economic factors influencing both online and offline political engagement and sheds light on how social media empowers younger voters by reducing their reliance on traditional influencers. Kerala’s social media trends align with those of developed nations like the USA, in contrast to broader Indian digital and gender divide indicators. The study also delves into the social media strategies of 280 successful candidates in the April 2019 Kerala Legislative Assembly elections, identifying the key factors influencing their electoral success. Notably, Facebook engagement metrics, such as shares and followers, emerge as more significant predictors of candidate winnability than Twitter metrics. The research highlights the profound impact of social media on political communication, perception, youth participation and candidate strategies, ultimately shaping electoral outcomes in Kerala. This study addresses a critical research gap regarding social media use among Kerala voters and the reciprocal strategies adopted by candidates, including the predictive impact on candidates’ performance.
The Connection Between Anatomical Substrate and Clinical Severity in Fetal Ebstein Anomaly
Authors: Coacci Sara , Alston Erin L. J. , Yamasaki Takato , Ronai Christina , Sanders Stephen P. , Carreon Chrystalle Katte
Published: May 2024

Ebstein anomaly (EA) is a rare congenital heart defect characterized by abnormal development of the tricuspid valve (TV) and right ventricular myocardium. This study documents 2 dramatic cases of fetal EA characterized by hydrops and cardiomegaly, leading to intrauterine or early neonatal death. These clinical outcomes were associated with morphological abnormalities including severe tricuspid regurgitation, unguarded TV orifice, pulmonary atresia, and flattened right ventricular myocardium. This study highlights that these adverse anatomical features may result in unfavorable clinical outcomes in fetal EA. While timely identification of such features by prenatal ultrasound is crucial for providing accurate prognostic stratification and guiding treatment decisions, fetopsy may be necessary to discern EA among the spectrum of right-heart anomalies.
Europe and Arab States’ Migration-related Instruments with Africa: Dilemma of Soft Power and Conflictual Interests
Authors: Akpomera Edward
Published: May 2024

The national and regional interests of the European Union, oil-rich Gulf Cooperation Council and Africa are conflictual in addressing international labour migration. This underscores the structure and ineffectiveness of bilateral migration instruments. The European Union canvasses for migrants’ returns, readmission and outsourcing of national border controls; Arab states show reluctance to stop the predominant employer–sponsorship system that curtails labour migrants’ human rights, while African states detest migrants’ return and readmission, and prefer liberalisation of legal migration and flow of remittances. This article is anchored on the hegemonic stability and regime frame of interventionist liberalism theoretical perspectives to highlight Europe’s soft power in migration partnerships or agreements deployed via financial aid and development projects as a way to drive the migration-development-security nexus with African countries. Essentially, African states’ asymmetric economic relationship with Europe has accentuated the carrot-and-stick approach, while Arab states’ slow pace in allowing the mobility of African labour migrants has led to a reduction in remittance flows. It is recommended that the dialogues between the regional blocs and countries leading to labour migration agreements must find a common ground of mutual interests for effective partnerships to emerge.
Aqueous humor proteomics analyzed by bioinformatics and machine learning in PDR cases versus controls
Authors: Wang Tan , Chen Huan , Li Ningning , Zhang Bao , Min Hanyi
Published: May 2024

Background

To comprehend the complexities of pathophysiological mechanisms and molecular events that contribute to proliferative diabetic retinopathy (PDR) and evaluate the diagnostic value of aqueous humor (AH) in monitoring the onset of PDR.

Methods

A cohort containing 16 PDR and 10 cataract patients and another validation cohort containing 8 PDR and 4 cataract patients were studied. AH was collected and subjected to proteomics analyses. Bioinformatics analysis and a machine learning-based pipeline called inference of biomolecular combinations with minimal bias were used to explore the functional relevance, hub proteins, and biomarkers.

Results

Deep profiling of AH proteomes revealed several insights. First, the combination of SIAE, SEMA7A, GNS, and IGKV3D-15 and the combination of ATP6AP1, SPARCL1, and SERPINA7 could serve as surrogate protein biomarkers for monitoring PDR progression. Second, ALB, FN1, ACTB, SERPINA1, C3, and VTN acted as hub proteins in the profiling of AH proteomes. SERPINA1 was the protein with the highest correlation coefficient not only for BCVA but also for the duration of diabetes. Third, “Complement and coagulation cascades” was an important pathway for PDR development.

Conclusions

AH proteomics provides stable and accurate biomarkers for early warning and diagnosis of PDR. This study provides a deep understanding of the molecular mechanisms of PDR and a rich resource for optimizing PDR management.
Storz professional image enhancement system (SPECTRA A) enhancing detection of carcinoma urinary bladder by white light cystoscopy
Authors: Gnyawali Diwas , Sigdel Prem Raj , Rai Bipendra D. K. , Chapagain Suman , Gyawali Prem Raj
Published: May 2024

Background

SPECTRA A filters red light from white light through software to create contrast for better tissue visualization and light penetration. We aim to find whether the detection rate of bladder cancer is enhanced by SPECTRA A in adjunct to White Light Cystoscopy (WLC).

Methods

This was a prospective observational study among 66 patients in the Department of Urology and Kidney Transplant Surgery, Tribhuvan University Teaching Hospital. All patients undergoing TURBT for suspected/diagnosed bladder tumor were evaluated with WL, followed by SPECTRA A mode, and findings were recorded using visual bladder mapping. Resection of the tumor was done on WL, margins were again reevaluated using SPECTRA A mode, and a biopsy was taken in cases of suspicious findings confirmed on SPECTRA A. Tumor detection rate (sensitivity), extra lesion detection, false positive rate, and margin status were evaluated through 2 × 2 tables, McNemar chi-square test on patient level as well as lesion level.

Results

A total of 64 patients were included in the study. The mean age was 62.20 ± 13.98 with a sex ratio of M:F 4.3:1. SPECTRA A and WL had a detection rate of 95.33% and 78.80% (p = 0.001), respectively, and positive biopsy of detected lesions was 78.8% and 84.13% (p = 0.041), respectively, for SPECTRA A and WL. The false positive rate of SPECTRA A and WL was 21.19% and 15.86% (p = 0.006), respectively, whereas the false negative rate was 4% and 19.2% (p = 0.001), respectively. The number of extra lesions detected by SPECTRA A was 39, out of which 29 were histologically proven tumors.

Conclusion

SPECTRA A enhances the detection rate of bladder cancer when used with WL. We can increase the detection of bladder cancer by using a combination of white light and SPECTRA A.
Effect of novel anti-tumor and anti-angiogenesis drug taurolactone on angiogenic factor AGGF1 and angiogenesis mimicry in patients with hepatocellular carcinoma
Authors: Liu Shaoping , Wei Yinzhi , Nie Lei , Tang Ze , Lu Qi , Liang Qun
Published: May 2024

Objective

Our study was to investigate the impact of taurolactone, a novel anti-tumor and anti-angiogenic drug, on AGGF1, an angiogenic factor, and angiogenesis mimicry in patients diagnosed with hepatocellular carcinoma (HCC).

Methods

A total of 120 HCC patients were enrolled from the Department of Oncology and Hepatobiliary Surgery at our hospital between May 2021 and December 2022. HCC diagnoses were confirmed through imaging or tissue biopsy for all patients. The age of patients ranged from 37 to 72 years, with an average age of 64.29 ± 4.58 years. These participants were divided equally into two groups: the control group and the observation group, each consisting of 60 individuals. While the control group received standard drug treatment, the observation group was administered taurolactone treatment. Before being included in the study, all participants or their legal representatives provided signed informed consent. Patient demographic information was collected through a questionnaire survey. ELISA was used to measure the levels of VEGF and AGGF1 in patients following treatment. Western blot was applied to assess the protein expression of PDGF, Angiopoietin, and AGGF1. MRI imaging technology was utilized to assess the perfusion characteristics of tumor blood vessels in patients. Tumor vessel density was compared between patients using ultrasonography. We also conducted a comparison between the two groups in terms of progression-free survival and overall survival.

Results

General patient information between the two groups showed no significant differences (P > 0.05). Of note, the observation group exhibited greatly lower levels of VEGF and AGGF1 compared to the control group (P < 0.05). Moreover, the levels of PDGF, Angiopoietin, and AGGF1 protein expression were significantly reduced in the observation group compared to the control group (P < 0.05). In terms of tumor perfusion, the observation group displayed lower average and maximum perfusion volumes in tumor blood vessels compared to the control group (P < 0.05). Additionally, the observation group demonstrated delayed peak times and arrival times of tumor blood vessels in comparison to the control group (P < 0.05). Furthermore, the density of tumor blood vessels was notably lower in the observation group compared to the control group (P < 0.05). Patients in the observation group had longer progression-free survival and overall survival than the control group (P < 0.05).

Conclusion

In HCC patients, our study highlighted the potential efficacy of taurolactone treatment as it effectively inhibited angiogenic factors and angiogenesis mimicry, ultimately leading to an improved prognosis for these patients.
The prevalence and possible risk factors of gaming disorder among adolescents in China
Authors: Zhang Lina , Han Jiaqi , Liu Mengqi , Yang Cheng , Liao Yanhui
Published: May 2024

Background

Nowadays, moderate gaming behaviors can be a pleasant and relaxing experiences among adolescents. However, excessive gaming behavior may lead to gaming disorder (GD) that disruption of normal daily life. Understanding the possible risk factors of this emerging problem would help to suggest effective at preventing and intervening. This study aimed to investigate the prevalence of GD and analyze its possible risk factors that adolescents with GD.

Methods

Data were collected between October 2020 and January 2021. In total, a sample of 7901 students (4080 (52%) boys, 3742 (48%) girls; aged 12–18 years) completed questionnaires regarding the Gaming-Related Behaviors Survey, Gaming Disorder Symptom Questionnaire-21 (GDSQ-21); Behavioral Inhibition System and Behavioral Activation System Scale (BIS/BAS Scale); Emotion Regulation Questionnaire (ERQ); Short-form Egna Minnenav Barndoms Uppfostran for Chinese (s-EMBU-C); and Adolescent Self-Rating Life Events Checklist (ASLEC).

Results

The prevalence of GD was 2.27% in this adolescent sample. The GD gamers were a little bit older (i.e., a higher proportion of senior grades), more boys, with more gaming hours per week in the last 12 months, with more reward responsiveness, maternal rejecting and occurrence of negative life events (e.g., interpersonal relationships, being punished and bereavement factors).

Conclusion

These possible risk factors may influence the onset of GD. Future research in clinical, public health, education and other fields should focus on these aspects for provide target prevention and early intervention strategies.
NGEF is a potential prognostic biomarker and could serve as an indicator for immunotherapy and chemotherapy in lung adenocarcinoma
Authors: Chen Xin , Zhang Tao , He Yan-qiu , Miao Ti-wei , Yin Jie , Ding Qian , Yang Mei , Chen Fang-ying , Zeng Hong-ping , Liu Jie , Zhu Qi
Published: May 2024

Background

Neuronal guanine nucleotide exchange factor (NGEF) plays a key role in several cancers; however, its role in lung adenocarcinoma (LUAD) remains unclear. The aim of this study was to evaluate the efficacy of NGEF as a prognostic biomarker and potential therapeutic target for LUAD.

Methods

NGEF expression data for multiple cancers and LUAD were downloaded from multiple databases. The high- and low-NGEF expression groups were constructed based on median NGEF expression in LUAD samples, and then performed Kaplan–Meier survival analysis. Differentially expressed genes (DEGs) from the two NGEF expression groups were screened and applied to construct a protein-protein interaction network. The primary pathways were obtained using gene set enrichment analysis. The associations between NGEF expression and clinical characteristics, immune infiltration, immune checkpoint inhibitors (ICIs), sensitivity to chemotherapy, and tumor mutation burden (TMB) were investigated using R. Levels of NGEF expression in the lung tissue was validated using single-cell RNA sequencing, quantitative polymerase chain reaction (qPCR), immunohistochemical staining, and western blot analysis.

Results

The expression of NGEF mRNA was upregulated in multiple cancers. mRNA and protein expression levels of NGEF were higher in patients with LUAD than in controls, as validated using qPCR and western blot. High NGEF expression was an independent prognostic factor for LUAD and was associated with advanced tumor stage, large tumor size, more lymph node metastasis, and worse overall survival (OS). A total of 182 overlapping DEGs were screened between The Cancer Genome Atlas and GSE31210, among which the top 20 hub genes were identified. NGEF expression was mainly enriched in the pathways of apoptosis, cell cycle, and DNA replication. Moreover, elevated NGEF expression were associated with a high fraction of activated memory CD4+ T cells and M0 macrophages; elevated expression levels of the ICIs: programmed cell death 1 and programmed cell death 1 ligand 1 expression; higher TMB; and better sensitivity to bortezomib, docetaxel, paclitaxel, and parthenolide, but less sensitivity to axitinib and metformin.

Conclusion

NGEF expression is upregulated in LUAD and is significantly associated with tumor stages, OS probability, immune infiltration, immunotherapy response, and chemotherapy response. NGEF may be a potential diagnostic and prognostic biomarker and therapeutic target in LUAD.
Monitoring COPD patients: systemic and bronchial eosinophilic inflammation in a 2-year follow-up
Authors: Pignatti Patrizia , Visca Dina , Zappa Martina , Zampogna Elisabetta , Saderi Laura , Sotgiu Giovanni , Centis Rosella , Migliori Giovanni Battista , Spanevello Antonio
Published: May 2024

Background

High blood eosinophils seem to predict exacerbations and response to inhaled corticosteroids (ICS) treatment in patients with chronic obstructive pulmonary disease (COPD). The aim of our study was to prospectively evaluate for 2 years, blood and sputum eosinophils in COPD patients treated with bronchodilators only at recruitment.

Methods

COPD patients in stable condition treated with bronchodilators only underwent monitoring of lung function, blood and sputum eosinophils, exacerbations and comorbidities every 6 months for 2 years. ICS was added during follow-up when symptoms worsened.

Results

63 COPD patients were enrolled: 53 were followed for 1 year, 41 for 2 years, 10 dropped-out. After 2 years, ICS was added in 12/41 patients (29%) without any statistically significant difference at time points considered. Blood and sputum eosinophils did not change during follow-up. Only FEV1/FVC at T0 was predictive of ICS addition during the 2 year-follow-up (OR:0.91; 95% CI: 0.83–0.99, p = 0.03). ICS addition did not impact on delta (T24-T0) FEV1, blood and sputum eosinophils and exacerbations. After 2 years, patients who received ICS had higher blood eosinophils than those in bronchodilator therapy (p = 0.042). Patients with history of ischemic heart disease increased blood eosinophils after 2 years [p = 0.03 for both percentage and counts].

Conclusions

Blood and sputum eosinophils remained stable during the 2 year follow-up and were not associated with worsened symptoms or exacerbations. Almost 30% of mild/moderate COPD patients in bronchodilator therapy at enrollment, received ICS for worsened symptoms in a 2 year-follow-up and only FEV1/FVC at T0 seems to predict this addition. History of ischemic heart disease seems to be associated with a progressive increase of blood eosinophils.
Early cartilage lesion and 5-year incident joint surgery in knee osteoarthritis patients: a retrospective cohort study
Authors: Xiao-feng Liu , Jin-shan Zhang , Yong-qiang Zheng , Ze-feng Wang , Yong-quan Xu , Yang-zhen Fang , Zhen-yu Lin , Liang Lin , Hong-peng Zhang , Xiao-peng Huang
Published: May 2024

Objective

to investigate the association between cartilage lesion-related features observed in knee osteoarthritis (OA) patients’ first MRI examination and incident knee surgery within 5 years. Additionally, to assess the predictive value of these features for the incident knee surgery.

Methods

We identified patients diagnosed with knee OA and treated at our institution between January 2015 and January 2018, and retrieved their baseline clinical data and first MRI examination films from the information system. Next, we proceeded to determine joint space narrowing grade, cartilage lesion size grade, cartilage full-thickness loss grade and cartilage lesion sum score for the medial and lateral compartments, respectively. Generalized linear regression models examined the association of these features with 5-year incident knee surgery. Positive and negative predictive values (PPVs and NPVs) were determined referring to 5-year incident knee surgery.

Results

Totally, 878 participants (knees) were found eligible to form the study population. Within the 5 years, surgery was performed on 61 knees. None of the cartilage-related features had been found significantly associated with incident surgery. The results were similar for medial and lateral compartments. The PPVs were low for all the features.

Conclusions

Among symptomatic clinically diagnosed OA knees, cartilage lesions observed in the first MRI examinations were not found to be associated with the occurrence of joint surgery within a 5-year period. All these cartilage-related features appear to have no additional value in predicting 5-year incident joint surgery.
The influence of gender and sport on popliteal angle and dorsiflexion in junior high school students
Authors: Pietrzak Krzysztof , Bania Artur , Nowocień Krzysztof , Kraszewski Bartosz , Wiernicka Marzena
Published: May 2024

Background

The aim of the study was to assess factors affecting the popliteal angle and foot dorsiflexion, in particular gender. The subjects were 142 students from the 2nd and 3rd year of Poznań junior high schools.

Methods

The participants included 57 girls and 87 boys. Three raters examined each subject: a specialist in orthopaedics, a resident doctor and a physical therapy student.

Foot dorsal flexion was tested in a supine position with lower limbs extended. Next, dorsal flexion was evaluated with the knee and hip in 90 degrees of flexion. Finally, a passive knee extension (PKE) test was carried out. The significance of the PKE test is that the lower the angle the more flexible the hamstrings. This is because the PKE measurement is the distance to the right angle, that is a full knee extension with the hip flexed.

Results

The non-parametric test (Mann–Whitney) and the Student’s t-test showed differences between the female and male gender in the measurements of the popliteal angle (p < .05000). The correlation was negative, which means that the hamstrings are more flexible in girls. No differences were found between gender and passive foot dorsiflexion and dorsiflexion with a flexed hip and knee. No differences were found between the group with the extended PE curriculum and the group with the standard number of PE classes in the range of motion of foot dorsiflexion and the value of the popliteal angle.

Conclusions

Girls between 13 and 15 years old have a significantly larger hamstring flexibility, which is confirmed by the tests of the popliteal angle. No differences were found in dorsiflexion between girls and boys who have not been trained using a training model.
Accuracy and efficiency of dynamic navigated root-end resection in endodontic surgery: a pilot in vitro study
Authors: Liu Si-Min , Peng Li , Zhao Yi-Jiao , Han Bing , Wang Xiao-Yan , Wang Zu-Hua
Published: May 2024

Background

The operation accuracy and efficiency of dynamic navigated endodontic surgery were evaluated through in vitro experiments. This study provides a reference for future clinical application of dynamic navigation systems in endodontic surgery.

Materials and methods

3D-printed maxillary anterior teeth were used in the preparation of models for endodontic surgery. Endodontic surgery was performed with and without dynamic navigation by an operator who was proficient in dynamic navigation technology but had no experience in endodontic surgery. Optical scanning data were applied to evaluate the length and angle deviations of root-end resection. And the operation time was recorded. T tests were used to analyze the effect of dynamic navigation technology on the accuracy and duration of endodontic surgery.

Results

With dynamic navigation, the root-end resection length deviation was 0.46 ± 0.06 mm, the angle deviation was 2.45 ± 0.96°, and the operation time was 187 ± 22.97 s. Without dynamic navigation, the root-end resection length deviation was 1.20 ± 0.92 mm, the angle deviation was 16.20 ± 9.59°, and the operation time was 247 ± 61.47 s. Less deviation was achieved and less operation time was spent with than without dynamic navigation (P < 0.01).

Conclusion

The application of a dynamic navigation system in endodontic surgery can improve the accuracy and efficiency significantly for operators without surgical experience and reduce the operation time.
A polyphenol fraction from Rosa multiflora var. platyphylala reduces body fat in overweight humans through appetite suppression – a randomized, double-blind, placebo-controlled trial
Authors: Sudeep Heggar Venkataramana , Prithviraj Puwar , Jestin Thomas V , Shyamprasad Kodimule
Published: May 2024

Background

Rosa species are rich sources of polyphenols with physiological functions. In this study a polyphenol-rich Rosa multiflora (var. platyphylala) petal extract (RoseFit™) was investigated for weight loss in humans.

Methods

In a randomized, placebo-controlled, parallel-group, double-blind clinical trial seventy overweight male and female subjects (20–50 years) with body mass index (BMI) 25–30 kg/m2 were randomly allocated to the active treatment group (RoseFit) and placebo group in a 1:1 ratio. The subjects received 300 mg capsules twice daily for 12 weeks. The primary efficacy outcome measures included body weight, BMI, and body composition, as determined using Dual-energy X-ray absorptiometry (DEXA). Secondary measures consisted of serum lipid profile and appetite marker (leptin and ghrelin) analyses. Safety analyses included biochemical and hematological assessments.

Results

At the end of the study, a marked reduction in body weight (-1.20 ± 2.62 kg, p < 0.05) and BMI from baseline was observed in the RoseFit group. In addition, the body fat % (RoseFit = -1.69 ± 2.59%, placebo = 0.96 ± 3.21%; p < 0.001) and fat mass (RoseFit = -1.75 ± 1.80 kg, placebo = 1.61 ± 3.82 kg; p < 0.001) were significantly abated in RoseFit group. Importantly, the lean mass was maintained during the intervention. RoseFit ingestion significantly increased the serum leptin levels compared to the placebo (4.85%; p < 0.05). Further, RoseFit group showed reduction in the hunger hormone ghrelin level (2.27%; p < 0.001) from baseline to the end of study, compared to the placebo. The subjective evaluation of appetite using visual analog scale (VAS) questionnaires further confirmed the appetite-suppression effects of RoseFit. The lipid profile significantly improved in RoseFit-treated subjects. No serious adverse events were observed during the study, indicating the tolerability of RoseFit.

Conclusions

Supplementation with RoseFit significantly impacts body weight management and can thus be a potential nutraceutical ingredient for sustainable weight loss.

Trial registration

CTRI/2019/10/021584 dated 09/10/2019
Patient self-referral patterns in a developing country: characteristics, prevalence, and predictors
Authors: Hasan Mohammad Jahid , Rafi Md. Abdur , Nishat Nahida Hannan , Islam Ima , Afrin Nusrat , Ghosh Bikona , Kabir Etminan , Akhter Samiha Zaman , Poushi Maisha Zaman , Shahnoor Saadi Abdullah Bin , Fardous Jannatul , Tabassum Tamanna , Islam Sadia , Kalam Sumiya Bent , Aslam Mehjabeen Tasnuva , Joarder Taufique
Published: May 2024

Background

Efficient healthcare delivery and access to specialized care rely heavily on a well-established healthcare sector referral system. However, the referral system faces significant challenges in developing nations like Bangladesh. This study aimed to assess self-referral prevalence among patients attending tertiary care hospitals in Bangladesh and identify the associated factors.

Methods

This cross-sectional study was conducted at two tertiary care hospital, involving 822 patients visiting their outpatient or inpatient departments. A semi-structured questionnaire was used for data collection. The patients’ mode of referral (self-referral or institutional referral) was considered the outcome variable.

Results

Approximately 58% of the participants were unaware of the referral system. Of all, 59% (485 out of 822) of patients visiting tertiary care hospitals were self-referred, while 41% were referred by other healthcare facilities. The primary reasons for self-referral were inadequate treatment (28%), inadequate facilities (23%), critical cases (14%), and lack of expert physicians (8%). In contrast, institutional referrals were mainly attributed to inadequate facilities to treat the patient (53%), inadequate treatment (47%), difficult-to-treat cases (44%), and lack of expert physicians (31%) at the time of referral. The private facilities received a higher proportion of self-referred patients compared to government hospitals (68% vs. 56%, p < 0.001). Among patients attending the study sites through institutional referral, approximately 10% were referred from community clinics, 6% from union sub-centers, 25% from upazila health complexes, 22% from district hospitals, 22% from other tertiary care hospitals, and 42% from private clinics. Patients visiting the outpatient department (adjusted odds ratio [aOR] 3.3, 95% confidence interval [CI] 2.28–4.82, p < 0.001), residing in urban areas (aOR 1.29, 95% CI 1.04–1.64, p = 0.007), belonging to middle- and high-income families (aOR 1.34, 95% CI 1.03–1.62, p = 0.014, and aOR 1.98, 95% CI 1.54–2.46, p = 0.005, respectively), and living within 20 km of healthcare facilities (aOR 3.15, 95% CI 2.24–4.44, p-value < 0.001) exhibited a higher tendency for self-referral to tertiary care facilities.

Conclusions

A considerable number of patients in Bangladesh, particularly those from affluent urban areas and proximity to healthcare facilities, tend to self-refer to tertiary care centers. Inadequacy of facilities in primary care centers significantly influences patients to opt for self-referral.
Comprehensive insights into AML relapse: genetic mutations, clonal evolution, and clinical outcomes
Authors: Kim Namsoo , Hahn Seungmin , Choi Yu Jeong , Cho Hyunsoo , Chung Haerim , Jang Ji Eun , Lyu Chuhl Joo , Lee Seung-Tae , Choi Jong Rak , Cheong June-Won , Shin Saeam
Published: May 2024

Introduction

Acute myeloid leukemia (AML) is a complex hematologic malignancy characterized by uncontrolled proliferation of myeloid precursor cells within bone marrow. Despite advances in understanding of its molecular underpinnings, AML remains a therapeutic challenge due to its high relapse rate and clonal evolution.

Methods

In this retrospective study, we analyzed data from 24 AML patients diagnosed at a single institution between January 2017 and August 2023. Comprehensive genetic analyses, including chromosomal karyotyping, next-generation sequencing, and gene fusion assays, were performed on bone marrow samples obtained at initial diagnosis and relapse. Clinical data, treatment regimens, and patient outcomes were also documented.

Results

Mutations in core genes of FLT3, NPM1, DNMT3A, and IDH2 were frequently discovered in diagnostic sample and remained in relapse sample. FLT3-ITD, TP53, KIT, RUNX1, and WT1 mutation were acquired at relapse in one patient each. Gene fusion assays revealed stable patterns, while chromosomal karyotype analyses indicated a greater diversity of mutations in relapsed patients. Clonal evolution patterns varied, with some cases showing linear or branching evolution and others exhibiting no substantial change in core mutations between diagnosis and relapse.

Conclusions

Our study integrates karyotype, gene rearrangements, and gene mutation results to provide a further understanding of AML heterogeneity and evolution. We demonstrate the clinical relevance of specific mutations and clonal evolution patterns, emphasizing the need for personalized therapies and measurable residual disease monitoring in AML management. By bridging the gap between genetics and clinical outcome, we move closer to tailored AML therapies and improved patient prognoses.
Pharmacokinetics of tenofovir alafenamide, emtricitabine, and dolutegravir in a patient on peritoneal dialysis
Authors: Massih Sandra Abdul , Atta Mohamed G. , Thio Chloe L. , Tornheim Jeffrey A. , Fuchs Edward J. , Bakshi Rahul P. , Marzinke Mark A. , Hendrix Craig W. , Weld Ethel D.
Published: May 2024

Introduction

Peritoneal dialysis (PD) is an effective renal replacement modality in people with HIV (PWH) with end-stage kidney disease (ESKD), particularly those with residual kidney function. Data on pharmacokinetics (PK) of antiretrovirals in patients on peritoneal dialysis are limited.

Methods

A single-participant study was performed on a 49-year-old gentleman with ESKD on PD and controlled HIV on once daily dolutegravir (DTG) 50 mg + tenofovir alafenamide (TAF) 25 mg / emtricitabine (FTC) 200 mg. He underwent serial blood plasma, peripheral blood mononuclear cell, and urine PK measurements over 24 h after an observed DTG + FTC/TAF dose.

Results

Plasma trough (Cmin) concentrations of TAF, tenofovir (TFV), FTC, and DTG were 0.05, 164, 1,006, and 718 ng/mL, respectively. Intracellular trough concentrations of TFV-DP and FTC-TP were 1142 and 11,201 fmol/million cells, respectively. Compared to published mean trough concentrations in PWH with normal kidney function, observed TFV and FTC trough concentrations were 15.5- and 20-fold higher, while intracellular trough concentrations of TFV-DP and FTC-TP were 2.2-fold and 5.4-fold higher, respectively. TFV and FTC urine levels were 20 times lower than in people with normal GFR.

Conclusions

In a single ESKD PWH on PD, daily TAF was associated with plasma TFV and intracellular TFV-DP trough concentrations 15-fold and 2-fold higher than those of people with uncompromised kidney function, potentially contributing to nephrotoxicity. This suggests that TFV accumulates on PD; thus, daily TAF in PD patients may require dose adjustment or regimen change to optimize treatment, minimize toxicity, and preserve residual kidney function.
The ethnobotanical heritage of Lotkuh, a high-altitude tribal haven of Chitral, the Eastern Hindu Kush, Pakistan
Authors: Ullah Hafiz , Badshah Lal
Published: May 2024

Background

In northwestern Pakistan, Lotkuh is a high-altitude terrain nestled within the eastern Hindu Kush region. Enclaved by towering peaks and harboring a unique culture, the region mirrors the geographical and cultural diversity of Pakistan. In this geographically isolated region, a treasure trove of ethnobotanical knowledge unfolds through generations of interaction between the inhabitants and indigenous plants, resulting in a profound understanding of the plant uses in nutritional, medicinal, cultural, and ritual contexts. Thus, the study seeks to gather, analyze, and document the indigenous knowledge of plant utilization of the distinct tribal culture.

Methods

Through semi-structured questionnaires, inventory interviews, and participatory workshops, data were collected by engaging a cohort of 120 local respondents. The collected data were then classified into nine distinct use categories, following which quantitative indices were calculated.

Results

The research identified a total of 150 plant species spanning across 59 different families and categorized them into 9 distinct usage groups. Among these, Astragalus oihorensis, Astragalus owirensis, Cicer nuristanicum, Geranium parmiricum, and Rochelia chitralensis stand out as novel species with distinctive applications. Notably, medicinal use garnered 600 reports, while animal feed, veterinary applications, human consumption, and toxicity recorded 500, 450, 425, and 104 reports, respectively. Informant consensus was high ranging between 0.8 and 0.9 with most agreement on human food and animal feed category. Platanus orientalis and Juglans regia, with RFC 0.91, were the most cited. The Family Importance Value (FIV) of Juglandaceae and Platanaceae, each with an FIV of 0.91, and Capparidaceae with an FIV of 0.83 indicate the intricate role the families play.

Conclusions

In this study, we explore 150 ethnobotanical species, uncovering novel entries within ethnobotanical literature. Among these, several species showcase unique uses previously undocumented in Pakistani literature. Our research sheds light on the intricate interaction between plants and the distinct cultural landscape of the Lotkuh region.
Deformable registration of magnetic resonance images using unsupervised deep learning in neuro-/radiation oncology
Authors: Osman Alexander F. I. , Al-Mugren Kholoud S. , Tamam Nissren M. , Shahine Bilal
Published: May 2024

Purpose

Accurate deformable registration of magnetic resonance imaging (MRI) scans containing pathologies is challenging due to changes in tissue appearance. In this paper, we developed a novel automated three-dimensional (3D) convolutional U-Net based deformable image registration (ConvUNet-DIR) method using unsupervised learning to establish correspondence between baseline pre-operative and follow-up MRI scans of patients with brain glioma.

Methods

This study involved multi-parametric brain MRI scans (T1, T1-contrast enhanced, T2, FLAIR) acquired at pre-operative and follow-up time for 160 patients diagnosed with glioma, representing the BraTS-Reg 2022 challenge dataset. ConvUNet-DIR, a deep learning-based deformable registration workflow using 3D U-Net style architecture as a core, was developed to establish correspondence between the MRI scans. The workflow consists of three components: (1) the U-Net learns features from pairs of MRI scans and estimates a mapping between them, (2) the grid generator computes the sampling grid based on the derived transformation parameters, and (3) the spatial transformation layer generates a warped image by applying the sampling operation using interpolation. A similarity measure was used as a loss function for the network with a regularization parameter limiting the deformation. The model was trained via unsupervised learning using pairs of MRI scans on a training data set (n = 102) and validated on a validation data set (n = 26) to assess its generalizability. Its performance was evaluated on a test set (n = 32) by computing the Dice score and structural similarity index (SSIM) quantitative metrics. The model’s performance also was compared with the baseline state-of-the-art VoxelMorph (VM1 and VM2) learning-based algorithms.

Results

The ConvUNet-DIR model showed promising competency in performing accurate 3D deformable registration. It achieved a mean Dice score of 0.975 ± 0.003 and SSIM of 0.908 ± 0.011 on the test set (n = 32). Experimental results also demonstrated that ConvUNet-DIR outperformed the VoxelMorph algorithms concerning Dice (VM1: 0.969 ± 0.006 and VM2: 0.957 ± 0.008) and SSIM (VM1: 0.893 ± 0.012 and VM2: 0.857 ± 0.017) metrics. The time required to perform a registration for a pair of MRI scans is about 1 s on the CPU.

Conclusions

The developed deep learning-based model can perform an end-to-end deformable registration of a pair of 3D MRI scans for glioma patients without human intervention. The model could provide accurate, efficient, and robust deformable registration without needing pre-alignment and labeling. It outperformed the state-of-the-art VoxelMorph learning-based deformable registration algorithms and other supervised/unsupervised deep learning-based methods reported in the literature.
Adipose stem cells-derived small extracellular vesicles transport Thrombospondin 1 cargo to promote insulin resistance in gestational diabetes mellitus
Authors: Li Huaping , Yang Hao , Liu Jingyan , Yang Hedi , Gao Xinyu , Yang Xiaoying , Liu Zhou , Qian Qiaohui
Published: May 2024

Background

Gestational diabetes mellitus (GDM) is a highly prevalent disease and poses a significant risk to the health of pregnant women. Abdominal adipose tissue (AT) contributes to insulin resistance (IR) associated with GDM. However, the underlying mechanisms remain unclear.

Methods

In this study, we developed a mouse model of GDM by subjecting mice to a high-fat diet. We collected adipose-derived stem cells (ADSCs) from the abdominal and inguinal regions and examined their role in inducing IR in normal tissues through the secretion of small extracellular vesicles (sEVs). The sEVs derived from ADSCs isolated from GDM mice (ADSC/GDM) were found to inhibit cell viability and insulin sensitivity in AML12, a normal mouse liver cell line.

Results

Through proteomic analysis, we identified high levels of the thrombospondin 1 (Thbs1) protein in the sEVs derived from ADSC/GDM. Subsequent overexpression of Thbs1 protein in AML12 cells demonstrated similar IR as observed with ADSC/GDM-derived sEVs. Mechanistically, the Thbs1 protein within the sEVs interacted with CD36 and transforming growth factor (Tgf) β receptors in AML12 cells, leading to the activation of Tgfβ/Smad2 signaling. Furthermore, the administration of LSKL, an antagonistic peptide targeting Thbs1, suppressed Thbs1 expression in ADSC/GDM-derived sEVs, thereby restoring insulin sensitivity in AML12 cells and GDM mice in vivo.

Conclusions

These findings shed light on the intercellular transmission mechanism through which ADSCs influence hepatic insulin sensitivity and underscore the therapeutic potential of targeting the Thbs1 protein within sEVs.
Phase angle as an indicator of body composition and physical performance in handball players
Authors: Oliveira Silvino Valmir , Raffaela Barbosa Barros Kelly , Machado Brito Felipe , Matheus Dias Magalhães Francisco , Augusto Ferreira Carioca Antônio , César Carneiro Loureiro Adriano , Salvador Veras-Silva Acácio , Daniel Motta Drummond Marcos , Antonio Pereira dos Santos Marcos
Published: May 2024

Background

Phase angle (PhA), obtained from the bioimpedance analysis, is widely used in clinical situations and in sports. This study evaluated the association between PhA with body composition and physical performance of handball athletes.

Methods

43 national-level players (22.19 ± 3.86 years) of both sexes were evaluated regarding anthropometry, body composition, squat (SJ) and countermovement (CMJ) jumps, handgrip strength, and cardiorespiratory fitness.

Results

We verified a correlation between PhA of the whole body and fat-free mass (r = 0.511), body mass index (r = 0.307), and body fat % (r = -0.303). There was a positive correlation between PhA of the whole body and SJ (r = 0.376), CMJ (r = 0.419), and handgrip for the dominant hand (r = 0.448). Moreover, PhA of the upper limbs was more strongly correlated with handgrip for the dominant (r = 0.630) and non-dominant hand (r = 0.575) compared to PhA of the whole body considering both sexes. Similarly, segmental PhA had a stronger significant correlation with SJ (r = 0.402) and handgrip for the dominant hand (r = 0.482) in males, as well as CMJ (r = 0.602) in females, compared to PhA of the whole body.

Conclusion

PhA of the whole body was positively related to fat-free mass, body mass index, body fat %, and lower- and upper-limbs strength in handball athletes. Segmental PhA might be used as a tool for estimating lower and upper limbs performance considering the sex, in preference to the PhA of the whole body.
Fistulising skin metastases in Crohn’s disease: a case report and review of the literature
Authors: Elger Tanja , Loibl Johanna , Buechler Christa , Haferkamp Sebastian , Werner Jens , Drexler Konstantin , Hohenleutner Ulrich , Guelow Karsten , Kunst Claudia , Kandulski Arne , Goeggelmann Pia , Mueller Martina , Tews Hauke Christian
Published: May 2024

Background

Metastatic Crohn’s disease is a rare disorder characterized by various granulomatous skin lesions that occur independently of gastrointestinal tract involvement. However, currently there is no standardized care or specific treatment. Therapeutic approaches include immunosuppressive agents, such as corticosteroids, azathioprine, and monoclonal antibodies targeting inflammatory cytokines like tumor necrosis factor (TNF).

Case presentation

We present a case of a 29-year-old western European woman with significant blind ending abdominal subcutaneous fistulas and abscesses, who sought evaluation in the dermatology department. Histological examination revealed multiple epithelioid cell granulomas. There was no evidence of infectious or rheumatologic diseases such as sarcoidosis. The tentative diagnosis was metastatic Crohn’s disease, which was not related to an intestinal manifestation of the disease. The patient responded to infliximab but had to discontinue it due to an allergic reaction. Subsequent adalimumab treatment failed to induce clinical remission; thus, therapy was switched to ustekinumab, resulting in a positive response. Written informed consent for publication of their clinical details and clinical images was obtained from the patient.

For our study more than 1600 publications were screened for cases of metastatic Crohn’s disease on PubMed database. 59 case reports with 171 patients were included in the analysis and evaluated for localization, diagnostic and therapeutic approaches, and complications and were summarized in this review.

Conclusion

The successful ustekinumab treatment of a patient with metastatic Crohn's disease underscores the potential of this minimally investigated therapeutic option, highlighting the need for future treatment guidelines given the increasing prevalence of such cases.
Impact of contextual factors on new product development process: evidence from a large company in Thailand
Authors: Phongthiya Tinnakorn , Hirunsothorn Wattana , Pattanasak Photchanaphisut , Sopadang Apichat , Anantana Tanyanuparb
Published: May 2024

This research investigates the impacts of contextual factors, including organization-, project-, product-, and market-related factors, on New Product Development (NPD) process and explores how these factors shape the NPD process of the company within a specific context—a large-sized company in Thailand. By interviewing 11 managers from a large-sized company in Thailand, the findings reveal different impact of the contextual factors on the company’s NPD process. Based on these findings, we develop a practical NPD model to overcome company-specific challenges and, consequently, offer valuable insights to enhance the NPD process in similar contexts. Importantly, our findings suggest that innovative companies should strategically integrate the route-to-market for radical innovation into their NPD process because it enhances the customer perception of the innovation’s value before commercialization, leading to the success of NPD. Our empirical evidence fills the gaps in the literature regarding the practical configuration of NPD processes in developing countries as well as large-sized companies, acknowledging the variation in the NPD process that depends on contextual factors where innovation occurs. It also provides detailed insights beyond most existing studies that investigate correlation of factors with the NPD process and offers practical implications for management involved in the NPD process, emphasizing the need for contextual awareness in formulating effective NPD strategies.