bluuebunny/crossref_metadata_2025 huggingface dataset:
Compliance in the laboratory: Navigating the Controlled Substances Act and Federal Analogue Act in scientific research
Authors: Chew Kimberly I , von Salm Jacqueline L
Published: September 2024

This paper delves into the crucial yet complex relationship between federal laws and scientific research, centering on the Controlled Substances Act (CSA) and the Federal Analogue Act (FAA). The CSA classifies substances into schedules, dictating the scope of scientific inquiry, particularly for Schedule I drugs, which have no recognized medical use and high potential for abuse. Researchers interested in these substances face a rigorous registration process, ensuring scientific advancements adhere to legal constraints. On the other hand, the FAA targets substances similar in structure and effect to controlled drugs, treating them as Schedule I if intended for human consumption. This presents a significant challenge to researchers who must meticulously assess legal risks and compliance to avoid inadvertent infringements. Compounds only an atom away from being classified as non-hallucinogenic can skirt the borders of legality, requiring carefully navigated research paths. Within this framework, researchers are tasked with navigating a maze of regulations—securing permits, conducting ethically-approved studies, and keeping detailed records. These efforts are critical for preserving the integrity and legitimacy of scientific work. In summary, the CSA and FAA are cornerstones of legal guidance for research related to controlled substances. They necessitate a proactive, well-informed research approach ensuring adherence to evolving legal standards and reinforcing the foundational values of responsible scientific practice. Compliance with these acts not only mitigates against the proliferation of illicit drugs but also consolidates the ethical pursuit of scientific knowledge.
Understanding COVID-19 vaccine hesitancy of different regions in the post-epidemic era: A causality deep learning approach
Authors: Liu Yang , Zhao Chenxu , Zhang Chengzhi
Published: September 2024

Objective

This paper aims to understand vaccine hesitancy in the post-epidemic era by analyzing texts related to vaccine reviews and public attitudes toward three prominent vaccine brands: Sinovac, AstraZeneca, and Pfizer, and exploring the relationship of vaccine hesitancy with the prevalence of epidemics in different regions.

Methods

We collected 165629 Twitter user comments associated with the vaccine brands. The comments were labeled based on willingness and attitude toward vaccination. We utilize a causality deep learning model, the Bert multi-channel convolutional neural network (BertMCNN), to predict users’ willingness and attitude mutually.

Results

When applied to the provided dataset, the proposed BertMCNN model demonstrated superior performance to traditional machine learning algorithms and other deep learning models. It is worth noting that after March 2022, the public was more hesitant about the Sinovac vaccines.

Conclusions

This study reveals a connection between vaccine hesitancy and the prevalence of the epidemic in different regions. The analytical results obtained from this method can assist governmental health departments in making informed decisions regarding vaccination strategies.
Intention to use patient portal and its predictors among patient with diabetes in Amhara region referral hospitals, Northwest Ethiopia, 2023: UTAUT-2 model
Authors: Wubete Abebe Aschale , Tilahun Binyam Chakilu , Mekonnen Zeleke Abebaw , Tegegne Masresha Derese
Published: September 2024

Background

Patient portal technology is increasingly utilized in the health care system for diabetes management as a means of communication and information-sharing tools, and it has the potential to improve access, quality, and outcomes for patients with diabetes. However, its adaptation is very low, and patients’ intention toward the patient portal is unknown. This study aims to fill this gap by determining the intention to use the patient portal and its predictors among patients with diabetes in Ethiopia.

Method

An institution-based cross-sectional study was conducted on patients with diabetes from April 3 to May 8 in eight referral hospitals in the Amhara region, Ethiopia 2023. Samples were proportionally allocated for each hospital, and participants were selected by using a systematic random sampling method. The data were collected by using an interviewer-administered questionnaire using the Kobo collection mobile app. Descriptive statistics were performed using SPSS version 26. The degree of association between exogenous and endogenous variables was assessed and validated using structural equation modeling using AMOS version 21.

Result

A total of 1037 (96.2% response rate) patients with diabetes participated in the study. Of them, 407 (39.25%), 95% CI: [36.4–42.2] were found to have an intention to use the patient portal. Digital literacy (β = 0.312, 95% CI: [0.154–0.465], p < .01), performance expectancy (β = 0.303, 95% CI: [0.185–0.420], p < .01), effort expectancy (β = 0.25, 95% CI: [0.131–0.392], p < 0.01) facilitating condition (β = 0.22, 95% CI: [0.081–0.36], p < .01) and habit (β = 0.111, 95% CI: [−0.009 to 0.227], p < .05) were significantly associated with the intention to use patient portals. Effort expectancy and facilitating conditions were positively moderated by gender.

Conclusion

This study found that patient with diabetes’ intention to use patient portals was low. To increase patients with diabetes’ intention to use the patient portal, interventions in digital literacy, performance expectations, effort expectations, facilitating conditions, and habits are required.
“I’m still struggling with it, and it scares me”: A qualitative analysis of older adults’ experiences with digital health portals during and after COVID-19
Authors: Hvalič-Touzery Simona , Laznik Jerneja , Petrovčič Andraž
Published: September 2024

Objective

The scaling of digital health platforms, accelerated by the COVID-19 pandemic, has globally reshaped the delivery of healthcare services, presenting both opportunities and challenges. Ensuring equitable access, especially for digitally disadvantaged groups, is a critical concern, and this study explores older adults’ perspectives on digital health platforms during and after the COVID-19 pandemic and examines their strategies for coping with the general challenges of the digitalization of health.

Methods

A total of 77 older adults (aged at least 65), including both internet users and non-users, participated in 11 focus group sessions in Slovenia between September and December 2022. Hybrid thematic analysis was used to develop an understanding of the challenges confronted by older adults in the digital health landscape.

Results

Three key themes emerged from the focus group sessions, which highlight digital inequalities that impact access to digital health platforms and their services: the challenges of digitalized health services, coping with these challenges, and the outcomes of health service digitalization. The “digital health paradox” is evident, in which opportunities are provided for some while access is limited for those unwilling or unable to use digital health platforms. Proxy users, often family or friends, help bridge this gap.

Conclusions

Ensuring the availability and viability of traditional health service access is crucial for empowering older adults to choose between digital health platforms and alternatives. Recognizing the importance of traditional approaches is vital, and healthcare providers and policymakers should prioritize inclusivity to ensure a diverse and equitable healthcare system for older adults and vulnerable populations.
Towards full remote programming for deep brain stimulation in Parkinson's disease: A case series
Authors: Wan Xiaonan , Lin Zhengyu , Duan Chengcheng , Zeng Zhitong , Zhang Chencheng , Li Dianyou
Published: September 2024

People with Parkinson's disease (PwPD) who undergo deep brain stimulation (DBS) surgery could benefit from remote programming (RP), which has proven to be both effective and economical. However, there is limited research on PwPD with DBS implants who have completed all programming sessions exclusively through remote means (full remote programming, FRP). This case report documents the experiences of five PwPD who underwent FRP, with four demonstrating improvements in motor symptoms, quality of life, and medication reduction. A total of 22 postoperative programming sessions were conducted, all via RP. FRP integrates RP with online consultations. Our findings contribute preliminary evidence supporting the feasibility and safety of FRP in the postoperative care of PwPD with DBS implants.
Protective Factors Against Suicidal Behaviors Among Community-Dwelling Rural Older Adults
Authors: Yoon Sukyung , Strong Joe , Grife Jamie
Published: September 2024

Suicide among older adults in rural areas is widespread. However, research on this issue is rare, and studies focusing on protective factors against suicidal behavior among this population are even scarcer. Based on Bronfenbrenner’s ecological framework, this systematic literature review examined protective factors against suicidal behavior among community-dwelling older adults in rural areas. The results found that there were individual-, family-, and community-level protective factors against suicidal behavior. Multi-level interventions are needed to reduce and prevent suicidal behavior among older adults in rural areas. Cultural differences should also be considered.
Challenges and Strategies in Pediatric Critical Care: Insights From Low-Resource Settings
Authors: Olatunji Gbolahan , Kokori Emmanuel , Aderinto Nicholas , Abdul Anoud , Tsoi Vincent , Mohamed Lamyaa , Alsabri Hussein Alsabri Mohammed
Published: September 2024

Background. Pediatric critical care in low-resource settings faces challenges like inadequate infrastructure, limited personnel, financial constraints, and cultural considerations, leading to poor outcomes for critically ill children. Methods. This review synthesizes information from 2 articles on pediatric intensive care units (PICUs) in low- and middle-income countries (LMICs). It identifies challenges such as high care costs, cultural preferences, and resource allocation issues. Results. Challenges include the financial burden of care, limited resources, and the need for external funding. Family preferences impact healthcare decisions, leading to ethical dilemmas. Resource allocation issues affect patient outcomes, including delayed diagnoses and high mortality rates. Conclusion. Addressing these challenges requires a multifaceted approach involving governments, healthcare providers, and international stakeholders. Standardizing care, investing in infrastructure and training, and promoting collaboration are essential to improving pediatric critical care and ensuring equitable access.
Embracing Generational Labels: An Analysis of Self-Identification and Political Partisanship
Authors: Lindner Andrew M. , Stelboum Sophia , Hakim Azizul
Published: September 2024

Despite the popularity of generational labels like Boomers, Gen X, Millennials, and Gen Z in mass media, social scientists have debated their usefulness and accuracy in research. Consequently, little is known about the actual rate of self-identification with these generational labels in the U.S. population. This study investigated these labels as social identities and examined the extent of intragenerational variation in identification rates by birth year. Additionally, we explored the associations among political partisanship, demographic factors, and generational self-identification. Using logistic regression analyses of data from a nationally representative survey of 1,478 Americans, we find that a majority of respondents self-identify with a generational label, but individuals with birth years in the middle of the generational range exhibit much higher rates of self-identification. However, our analysis reveals little evidence for variation in generational self-identification based on party, race, or other demographic characteristics.
A Validation Study of the Mindfulness-Based Interventions Teaching Assessment Criteria for Assessing Mindfulness-Based Intervention Teacher Skill: Inter-Rater Reliability and Predictive Validity
Authors: Hecht Frederick M , Crane Rebecca S , Moran Patricia , Kuyken Willem , Hartogensis Wendy , Brewer Judson
Published: September 2024

Background

Prior data suggests the Mindfulness-Based Interventions: (MBI) Teaching Assessment Criteria (MBI:TAC) has good inter-rater reliability, but many raters knew teacher experience level.

Objective

We sought to further evaluate the MBI-TAC’s inter-rater reliability and obtain preliminary data on predictive validity.

Methods

We videorecorded 21 MBSR teachers from academic and community settings. We trained 19 experienced MBI teachers in using the MBI:TAC. MBSR teachers were rated by three assessors; teachers and their assessors did not know one another. To assess predictive validity, MBSR students in courses taught by 18 of the MBSR teachers were invited to complete PROMIS-29 measures before the MBSR course, at the end of the course (month 2), and month 4.

Results

Intraclass correlation coefficients (ICCs) representing a single rater ranged from 0.33 to 0.56 on the 6 MBI:TAC domains. Using an average of two raters, ICC estimates ranged from 0.48 to 0.71 and ICCs generalizing to an average of three raters ranged from 0.6 to 0.8. Among n = 152 participating MBSR students, we found improvements from baseline to 2 months and 4 months in PROMIS measures of Anxiety, Depression, Fatigue, Sleep, and Social Role function (range in improvement 2.3 to 6.3, P < 0.0001 for all comparisons except Social Role at 2 months, P = 0.007). Higher MBI:TAC ratings were associated with greater improvements in anxiety among MBSR students from baseline to 2 months, with a −0.31 lower participant anxiety score per 1 unit increase in MBI:TAC composite teaching rating (95% CI −0.58, −0.05, P = 0.019), but we did not find statistically significant relationships with improvements in other PROMIS-29 domains.

Conclusions

ICCs indicated good reliability using an average of three ratings, but inter-rater reliability was only fair using a single rater. We found initial validation that higher MBI:TAC ratings predicted greater improvements in anxiety symptoms in MBSR participants.
Impact of soluble BCMA and non–T-cell factors on refractoriness to BCMA-targeting T-cell engagers in multiple myeloma
Authors: Lee Holly , Durante Michael , Skerget Sheri , Vishwamitra Deeksha , Benaoudia Sacha , Ahn Sungwoo , Poorebrahim Mansour , Barakat Elie , Jung David , Leblay Noémie , Ziccheddu Bachisio , Diamond Benjamin , Papadimitriou Marios , Cohen Adam D. , Landgren Ola , Neri Paola , Maura Francesco , Bahlis Nizar J.
Published: September 2024

Adoptive T-cell therapy is a promising therapy for multiple myeloma (MM), but its efficacy hinges on understanding the relevant biologic and predictive markers of response. B-cell maturation antigen (BCMA) is a key target antigen in MM with active development of multiple anti-BCMA T-cell engagers (TCEs) and chimeric antigen receptor T-cell therapies. The regulation of surface BCMA expression by MM cells, which leads to shedding of soluble BCMA (sBCMA), has triggered debate about the significance of sBCMA as a predictive marker and its potential impact on treatment outcomes. To address this, we leveraged whole-genome sequencing and in vitro assays to demonstrate that sBCMA may independently predict primary refractoriness to anti-BCMA therapies. In addition to sBCMA, tumor burden and surface BCMA antigen density collectively influenced the anti-BCMA TCE cytotoxic efficacy. Correlative analyses of 163 patients treated with the anti-BCMA TCE teclistamab validated and further underscored the association between elevated baseline sBCMA (>400 ng/mL) and refractoriness. Importantly, increasing the TCE dose, using TCE against alternative targets (eg, GPRC5D), and gamma secretase inhibitors were able to overcome the high sBCMA levels. These findings highlight the importance of taking into account the baseline sBCMA levels, disease burden, and TCE dose intensity when administering anti-BCMA TCEs, thereby offering critical insights for optimizing therapeutic strategies to overcome specific high-risk features and primary anti-BCMA TCE refractoriness.
Common single nucleotide polymorphisms associated with idiopathic pulmonary fibrosis: a systematic review
Authors: Dhooria Sahajal , Sharma Riya , Bal Amanjit , Sehgal Inderpaul Singh , Kashyap Dharambir , Muthu Valliappan , Prasad Kuruswamy Thurai , Agarwal Ritesh , Aggarwal Ashutosh Nath
Published: September 2024

Background

Several genetic variants are associated with the risk of idiopathic pulmonary fibrosis (IPF). These have not been systematically reviewed.

Methods

We searched the PubMed, Embase and GWAS Catalog databases for studies indexed between inception and 15 January 2024 describing genetic variants associated with IPF susceptibility. We included studies describing common associated single nucleotide polymorphisms (SNPs). We excluded studies describing rare variants, non-SNP variants and those without an allelic model analysis. We recorded study type, participant characteristics, genotyping methods, IPF diagnostic criteria, the SNPs and the respective genes, odds ratios, and other details. We also searched databases for functions of the identified genes.

Results

The primary search retrieved 2697 publications; we included 42 studies. There were nine genome-wide association/linkage studies, while 27 were candidate gene studies. The studies included 22–11 160 IPF subjects. 88 SNPs in 58 genes or loci were found associated with IPF susceptibility.MUC5Brs35705950 was the most studied SNP. Most (n=51) SNPs were in the intronic or intergenic regions; only 11 were coding sequence variants. The SNPs had odds ratios ranging from 0.27 to 7.82 for an association with IPF. Only 22 SNPs had moderate–large effects (OR >1.5 or <0.67). Only 49.1% of the associated genes have a known functional role in IPF; the role of G protein-related signalling and transcriptional regulation (zinc-finger proteins) remain unexplored.

Conclusion

Several common SNPs in over 50 genes have been found associated with IPF susceptibility. These variants may inform gene panels for future studies (PROSPERO CRD42023408912).
Bronchiectasis in Asia: a review of current status and challenges
Authors: Choi Hayoung , Xu Jin-Fu , Chotirmall Sanjay H. , Chalmers James D. , Morgan Lucy C. , Dhar Raja
Published: September 2024

Recent bronchiectasis studies from large-scale multinational, multicentre registries have demonstrated that the characteristics of the disease vary according to geographic region. However, most perspectives on bronchiectasis are dominated by data from Western countries. This review intends to provide an Asian perspective on the disease, focusing on the established registries in India, Korea and China. Asian patients with bronchiectasis are less likely to show female predominance and experience exacerbations, are more likely to be younger, have milder disease, and have fewer options for guideline-recommended treatment than those living in other global regions. Furthermore, Asian bronchiectasis patients demonstrate different comorbidities, microbiological profiles and unique endophenotypes, including post-tuberculosis and dry bronchiectasis. Notably, each Asian region reveals further geographic variations and inter-patient differences. Future studies are warranted to better characterise Asian patients with bronchiectasis.
Associations between vitamin D status and biomarkers linked with inflammation in patients with asthma: a systematic review and meta-analysis of interventional and observational studies
Authors: El Abd Asmae , Dasari Harika , Dodin Philippe , Trottier Helen , Ducharme Francine M.
Published: September 2024

Background

Numerous studies indicate an association between vitamin D status and inflammatory biomarkers in patients with asthma, but findings are inconsistent. This review aims to summarize the relationship between serum vitamin D status, assessed by 25-hydroxyvitamin D (25(OH)D) level, and inflammatory biomarkers in children and adults with asthma.

Methods

A literature search of interventional and observational studies on 25(OH)D up to November 2022 was conducted across six electronic databases. Outcomes of interest included a range of inflammatory biomarkers classified in four categories: T helper 2 (Th2) pro-inflammatory, non-Th2 pro-inflammatory, anti-inflammatory, and non-specific biomarkers. Study characteristics were extracted and risk of bias was evaluated using the American Academy of Nutrition and Dietetics tool. Meta-analysis was conducted on studies with a low risk of bias, while narrative reporting was used to present the direction of associations (positive, no association, or negative) for each biomarker, overall and within the low-risk studies.

Results

We included 71 studies (3 interventional, 68 observational) involving asthma patients. These studies investigated the association between serum 25(OH)D and Th2 pro-inflammatory biomarkers (N = 58), non-Th2 pro-inflammatory biomarkers (N = 18), anti-inflammatory biomarkers (N = 16), and non-specific biomarkers (N = 10). Thirteen (18.3%) studies, 50 (70.4%), and 8 (11.3%) were at high, moderate, and low risk of bias, respectively. In all studies, irrespective of risk of bias, the most frequently reported finding was no significant association, followed by a negative association between 25(OH)D and pro-inflammatory biomarkers and a positive association with anti-inflammatory biomarkers. In low-risk studies, one biomarker could be meta-analysed. The pooled estimate for 25(OH)D and serum IgE showed a negative association (β (95% CI)= − 0.33 (–0.65 to − 0.01); I2 = 88%; N = 4 studies). A negative association between 25(OH)D and blood eosinophils was also observed in the largest of three studies, as well as with cathelicidin (LL-37) in the only study reporting it. For other biomarkers, most low-risk studies revealed no significant association with 25(OH)D.

Conclusion

Serum 25(OH)D is negatively associated with serum IgE and possibly with blood eosinophils and LL-37, supporting an in vivo immunomodulatory effect of 25(OH)D. Future research should employ rigorous methodologies and standardized reporting for meta-analysis aggregation to further elucidate these associations.
A rare transcript homozygous variants in CLRN1(USH3A) causes Usher syndrome type 3 in a Chinese family
Authors: Wang Suyang , Xu Chen Yang , Zhu Yiming , Ding Wenjuan , Hu Jieyu , Xu Baicheng , Guo Yufen , Liu Xiaowen
Published: September 2024

Background

Usher syndrome type 3 (USH3) is an autosomal recessive inherited disorder caused by pathogenic variants in the CLRN1 gene.

Object

To evaluate the genotype-phenotype correlation of Usher syndrome type 3 (USH3) in a deaf-blind Chinese family of 3 generations with 2 patients.

Methods

We collected blood samples and clinical data from all of the pedigree family members. Genomic DNA was isolated from peripheral leukocytes using standard method. Targeted next generation sequencing and Sanger sequencing were performed to find the pathogenic variants in this family. Digital PCR and plasmid overexpression assay were used to verify the pathogenicity of variant sites in different transcripts.

Results

All patients developed bilateral sensorineural hearing loss (SHL), progressive vision loss and nyctalopia. NGS of genes for Usher syndrome, deafness and retinal dystrophy identified a locus mutation in CLRN1 that caused completely different amino acid changes in different transcripts[CLRN1:c.474T > A(P.Cys158Ter) at NM_001256819.2 or c.302T > A(p.Val101Asp) at NM_174878.3], and plasmid overexpression experiments confirmed that the c.474T > A(P.Cys158Ter, NM_001256819.2) was a pathogenic variant which has never been associated with Usher syndrome in China, and the transcript of this mutation was not the version commonly found worldwide.

Conclusions

The CLRN1c.474T > A(NM_001256819.2) mutation is the causative variant in the Chinese family with USH3. The pathogenicity of different transcripts should be particularly considered in pathogenicity analysis.
Mental health symptom burden in elite ice hockey players and its association with self-reported concussive events
Authors: Andersson Mitchell J. , Kenttä Göran , Claesdotter-Knutsson Emma , Håkansson Anders
Published: September 2024

Background

Some studies suggest that elite athletes experience adverse mental health symptoms at rates commensurate with the general population, despite the well-established buffering effects of exercise. Within contact sports, such as ice-hockey, recurrent concussions may be a source of this discrepancy. We compared the point prevalence of various mental health outcomes with other athlete and general population samples, as well as investigated their relationship with concussive events.

Methods

We surveyed 648 active ice hockey players from the top two men’s tiers and the top women’s tier in Swedish elite ice hockey on lifetime concussive events, hazardous alcohol use, problematic social media use, depression, anxiety, and burnout.

Results

Hazardous alcohol use was more prevalent among male ice hockey players (29.5% AUDIT-C ≥ 6) compared to other athlete and general population samples, while other mental health symptoms were less common. Female ice hockey players reported higher hazardous alcohol consumption (36.4% AUDIT-C ≥ 4) than another athlete sample and more burnout (19.1%) than the general population. After adjusting for covariates, athletes with 3+ concussive events had 2.1 times the odds of elevated depressive symptoms and 3.5 times the odds of elevated burnout symptoms compared to those with no concussion history. Treating lifetime concussive events as a continuous predictor revealed positive correlations with all outcomes except for hazardous alcohol use.

Conclusions

Mental health outcome rates among active elite ice hockey athletes differ from those of other athlete and general population samples, whilst concussive events may be particularly linked to elevated symptoms of depression and burnout.
Male football players have better patient-reported outcomes after primary anterior cruciate ligament reconstruction compared with females
Authors: Fältström Anne , Hägglund Martin , Kvist Joanna
Published: September 2024

Background

Sex differences in patient-reported outcomes (PROs) are not well investigated after anterior cruciate ligament (ACL) reconstruction in football players. The aim was to study sex differences in player-related factors, ACL injury characteristics and PROs after primary ACL reconstruction in football players.

Methods

In this cross-sectional cohort study a survey was sent to 390 male and 403 female football players who were injured when playing football and had undergone a primary ACL reconstruction in the previous 1–3 years. Player-related factors, ACL injury characteristics, and PROs covering knee function, satisfaction with activity level and knee function, and readiness to return to sport were compared between male and females. The questionnaires International Knee Documentation Committee Subjective Knee Evaluation Form (IKDC-SKF), Knee injury and Osteoarthritis Outcome Score (KOOS), ACL-Quality of Life (ACL-QoL) and ACL-Return to Sport after Injury (ACL-RSI) were used.

Results

Ninety males (23%) and 283 (70%) females answered the survey, 65 males and 198 females fulfilled the inclusion criteria. Males had returned to football to a higher degree (77% vs 59%, p = 0.008) at any time after ACL reconstruction, but at the time of the survey, an equal number of males and females played football (55% vs 47%, p = 0.239) and had similar activity level according to the Tegner Activity Score (median, 9; interquartile range [IQR], 7, vs median, 8; IQR, 7; p = 0.740). Males were more satisfied with their knee function and activity level and rated higher scores in the IKDC-SKF (mean ± standard deviation, 83 ± 16 vs 76 ± 16, p = 0.006), KOOS Sport/Recreation (79 ± 19 vs 72 ± 22, p = 0.034), KOOS Quality of Life (73 ± 22 vs 64 ± 20, p = 0.008), ACL-QoL (7.6 ± 2 vs 6.8 ± 1.8, p = 0.008), and ACL-RSI (6.7 ± 2.1 vs 5.5 ± 2.3, p < 0.001) than females (all with small − medium effect sizes).

Conclusions

Male football players reported more favourable results than females in patient-reported knee function, satisfaction with activity level and knee function, knee-related quality of life and psychological readiness to return to sport 1–3 years after ACL reconstruction. The results contribute to a better understanding of the eventual effect of patient sex on outcomes after ACL reconstruction in football players. However, the clinical importance of these differences is unclear.
Gene-variant specific effects of plasma amyloid-β levels in Swedish autosomal dominant Alzheimer disease
Authors: Johansson Charlotte , Thordardottir Steinunn , Laffita-Mesa José , Pannee Josef , Rodriguez-Vieitez Elena , Zetterberg Henrik , Blennow Kaj , Graff Caroline
Published: September 2024

Background

Several blood-based biomarkers offer the opportunity of in vivo detection of brain pathology and neurodegeneration in Alzheimer disease with high specificity and sensitivity, but the performance of amyloid-β (Aβ) measurements remains under evaluation. Autosomal dominant Alzheimer disease (ADAD) with mutations in PSEN1, PSEN2 and APP can be studied as a model for sporadic Alzheimer disease. However, clarifying the genetic effects on the Aβ-levels in different matrices such as cerebrospinal fluid or plasma is crucial for generalizability and utility of data. We aimed to explore plasma Aβ concentrations over the Alzheimer disease continuum in a longitudinal cohort of genetic Alzheimer disease.

Methods

92 plasma samples were collected from at-risk individuals (n = 47) in a Swedish cohort of ADAD, including 18 mutation carriers (13 APPswe (p.KM670/671NL) MC), 5 PSEN1 (p.H163Y) MC) and 29 non-carriers (NC) as the reference group. Concentrations of Aβ1–38, Aβ1–40 and Aβ1–42 were analyzed in plasma using immunoprecipitation coupled to tandem liquid chromatography mass spectrometry (IP-LC-MS/MS). Cross-sectional and repeated-measures data analyses were investigated family-wise, applying non-parametric tests as well as mixed-effects models.

Results

Cross-sectional analysis at baseline showed more than a 3-fold increase in all plasma Aβ peptides in APPswe MC, regardless of clinical status, compared to controls (p < 0.01). PSEN1 (p.H163Y) presymptomatic MC had a decrease of plasma Aβ1–38 compared to controls (p < 0.05). There was no difference in Aβ1–42/1–40 ratio between APPswe MC (PMC and SMC), PSEN1 MC (PMC) and controls at baseline. Notably, both cross-sectional data and repeated-measures analysis suggested that APPswe MC have a stable Aβ1–42/1–40 ratio with increasing age, in contrast to the decrease seen with aging in both controls and PSEN1 (p.H163Y) MC.

Conclusion

These data show very strong mutation-specific effects on Aβ profiles in blood, most likely due to a ubiquitous production outside of the CNS. Hence, analyses in an unselected clinical setting might unintentionally disclose genetic status. Furthermore, our findings suggest that the Aβ ratio might be a poor indicator of brain Aβ pathology in selected genetic cases. The very small sample size is a limitation that needs to be considered but reflects the scarcity of longitudinal in vivo data from genetic cohorts.
Explainable breast cancer molecular expression prediction using multi-task deep-learning based on 3D whole breast ultrasound
Authors: Huang Zengan , Zhang Xin , Ju Yan , Zhang Ge , Chang Wanying , Song Hongping , Gao Yi
Published: September 2024

Objectives

To noninvasively estimate three breast cancer biomarkers, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) and enhance performance and interpretability via multi-task deep learning.

Methods

The study included 388 breast cancer patients who received the 3D whole breast ultrasound system (3DWBUS) examinations at Xijing Hospital between October 2020 and September 2021. Two predictive models, a single-task and a multi-task, were developed; the former predicts biomarker expression, while the latter combines tumor segmentation with biomarker prediction to enhance interpretability. Performance evaluation included individual and overall prediction metrics, and Delong’s test was used for performance comparison. The models’ attention regions were visualized using Grad-CAM + + technology.

Results

All patients were randomly split into a training set (n = 240, 62%), a validation set (n = 60, 15%), and a test set (n = 88, 23%). In the individual evaluation of ER, PR, and HER2 expression prediction, the single-task and multi-task models achieved respective AUCs of 0.809 and 0.735 for ER, 0.688 and 0.767 for PR, and 0.626 and 0.697 for HER2, as observed in the test set. In the overall evaluation, the multi-task model demonstrated superior performance in the test set, achieving a higher macro AUC of 0.733, in contrast to 0.708 for the single-task model. The Grad-CAM + + method revealed that the multi-task model exhibited a stronger focus on diseased tissue areas, improving the interpretability of how the model worked.

Conclusion

Both models demonstrated impressive performance, with the multi-task model excelling in accuracy and offering improved interpretability on noninvasive 3DWBUS images using Grad-CAM + + technology.

Critical relevance statement

The multi-task deep learning model exhibits effective prediction for breast cancer biomarkers, offering direct biomarker identification and improved clinical interpretability, potentially boosting the efficiency of targeted drug screening.

Key Points

Tumoral biomarkers are paramount for determining breast cancer treatment.

The multi-task model can improve prediction performance, and improve interpretability in clinical practice.

The 3D whole breast ultrasound system-based deep learning models excelled in predicting breast cancer biomarkers.

Graphical Abstract
Prevalence of normal weight obesity and its cardiometabolic implications among government doctors in Gujarat, India: a cross-sectional study
Authors: M Yogesh , Trivedi Nidhi , Makwana Naresh , Krishna Pagadala Hari Priya PVM , D Kadalarasu
Published: September 2024

Background

Obesity is rising globally. Normal weight obesity (NWO) and normal weight central obesity (NWCO) despite normal BMI pose added metabolic risks. Limited data on these phenotypes among Indian doctors merits investigation. The present study aimed to assess the prevalence of overall obesity, NWO, NWCO, and their associations with cardiometabolic risks among doctors in Gujarat, India.

Methods

It’s a Cross-sectional study among 490 doctors aged 20–60 years at a tertiary hospital. Anthropometry, blood pressure, fasting glucose, and lipids were assessed. NWO was defined as a BMI of 18.5–24.9 kg/m2 with a high body fat percentage. NWCO as normal BMI and increased waist circumference. Body composition was assessed using an Omron body composition analyzer.

Results

The prevalence of overall obesity was 101 (20%), NWO 239 (48.7%), and NWCO 210 (42.8%). Mean BMI, blood pressure, glucose, and LDL increased from normal weight to NWO/NWCO groups (p < 0.05). NWO and NWCO had significantly higher odds of hypertension, dyslipidemia, and high fasting blood sugar compared to non-obese after adjusting for confounders.

Conclusion

The high burden of overall obesity, NWO, and NWCO among doctors highlights the need for lifestyle interventions to mitigate long-term cardiometabolic disease risk.
Optimum noise mechanism for differentially private queries in discrete finite sets
Authors: Kadam Sachin , Scaglione Anna , Ravi Nikhil , Peisert Sean , Lunghino Brent , Shumavon Aram
Published: September 2024

The differential privacy (DP) literature often centers on meeting privacy constraints by introducing noise to the query, typically using a pre-specified parametric distribution model with one or two degrees of freedom. However, this emphasis tends to neglect the crucial considerations of response accuracy and utility, especially in the context of categorical or discrete numerical database queries, where the parameters defining the noise distribution are finite and could be chosen optimally. This paper addresses this gap by introducing a novel framework for designing an optimal noise probability mass function (PMF) tailored to discrete and finite query sets. Our approach considers the modulo summation of random noise as the DP mechanism, aiming to present a tractable solution that not only satisfies privacy constraints but also minimizes query distortion. Unlike existing approaches focused solely on meeting privacy constraints, our framework seeks to optimize the noise distribution under an arbitrary $$(\epsilon , \delta )$$

(
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,
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constraint, thereby enhancing the accuracy and utility of the response. We demonstrate that the optimal PMF can be obtained through solving a mixed-integer linear program. Additionally, closed-form solutions for the optimal PMF are provided, minimizing the probability of error for two specific cases. Numerical experiments highlight the superior performance of our proposed optimal mechanisms compared to state-of-the-art methods. This paper contributes to the DP literature by presenting a clear and systematic approach to designing noise mechanisms that not only satisfy privacy requirements but also optimize query distortion. The framework introduced here opens avenues for improved privacy-preserving database queries, offering significant enhancements in response accuracy and utility.
Patients’ experience using an app for home remote monitoring of heart failure for a university hospital in Quebec, Canada
Authors: Vo Thi Xuan Hanh , Pomey Marie-Pascale , Charles Loyda Jean , Ribeiro Paula A. B. , Béchard Stéphanie , Rémillard Émilie , Grigoletti Shana , Nguyen John , Lehoux Pascale , Marier-Tétrault Emmanuel , Tournoux Francois
Published: September 2024

Background

The use of mobile health apps for remote monitoring has considerable potential for patient care. However, more research is needed to gather patients’ experience with their use. This study evaluates heart failure patients’ experience of the effects of remote monitoring on the management of heart failure (HF) using a smartphone app, the challenges faced in such use, and patients’ suggestions for improving the efficacy of this device.

Method

A qualitative study was conducted with all patients who had used the TakeCare™ app for at least three months during the exploratory phase of the Continuum project. Patients were recruited before COVID-19 began, and they used the app during this period. The app allows patients to submit their daily vital signs and answer questions about their symptoms to help the clinical professionals adjust their treatment plan as needed. Individual interviews were conducted by telephone or videoconference using a semi-structured individual interview guide. All interviews were recorded, transcribed and analyzed using the thematic analysis method.

Results

Of the 29 patients invited, 5 had since died, 10 did not respond, two gave positive feedback on the app but declined the interview, and 12 patients agreed to participate in an individual interview. The participants all liked the app’s ease of use. They particularly praised the contribution it made to monitoring their disease, both by themselves and by clinicians. The app also allowed them to stay connected to their clinical team and have better access to healthcare professionals. Patients suggested, as an improvement, that the feedback and communication features should be personalized to make them more individualized and interactive.

Conclusion

The TakeCare™ smartphone app was well received by patients with heart failure. Its use could facilitate better remote monitoring of heart conditions in the home as well as improve access to clinical teams.
Visualizing Inequities: A Step Toward Equitable Student Outcomes
Authors: Tatapudy Sumitra , Potter Rachel , Bostrom Linnea , Colgan Anne , Self Casey J. , Smith Julia , Xu Shangmou , Theobald Elli J.
Published: September 2024

Instructors must use data-informed reflection to interrogate course outcomes. However, these data can be hard to access, process, and visualize in ways that make patterns of inequities clear. To address this need, we developed an R-Shiny application that allows authenticated users to visualize inequities in student performance.
The Complex Dynamics of Indigenous Education in Mid-Twentieth-Century Ecuador as a Theater for Political Debate
Authors: Becker Marc
Published: September 2024

Activists in Ecuador established in the 1940s what have come to be remembered as the country's first Indigenous-run bilingual schools. Or at least this is the image that their founders presented when reflecting back on their achievements years later, and what has become fixed in the minds of subsequent educators. Archival records, however, present a more complicated picture. Rather than as “Indigenous” or “bilingual,” the recently formed Federación Ecuatoriana de Indios (Ecuadorean Federation of Indians) had created them as “syndicate” schools to mobilize against the racial discrimination and economic exploitation that agricultural workers faced on government-owned haciendas. In the process, organizers came into conflict with government policies that mandated the creation of public schools in rural communities and on haciendas. The competing school systems became an arena in which public policy debates were carried out with ramifications that extended to rival notions of how society should be properly organized.
Object, Room, Dwelling: Material Culture and the Indigenous City in the Colonial Andes
Authors: Mangan Jane E.
Published: September 2024

This article analyzes objects and abodes to further the understanding of lived experience in colonial Andean cities. It builds on existing scholarship on women's dress by analyzing household objects and even domestic structures themselves. Seeking to elaborate on Indigenous and mestiza women's experiences of the colonial city, the article draws primarily on notarial and judicial records for Arequipa, La Plata (today Sucre, Bolivia), and Potosí between the late 1500s and the mid-1600s. The essay opens with a discussion of the topu (Indigenous dress pin), moves to study the entirety of inventories held by specific city dwellers, and, finally, considers the significance of the domestic structure in terms of Indigenous urban experience. Through evidence of material culture and built environment, the article argues, we can gain a deeper understanding of the Indigenous cultural, social, and architectural identity of colonial cities in the face of Spanish presence.
A Problem as Much of Economic Theory as of Statistical Technique? The Walsh-Edgeworth Debate on Index Numbers, 1921–25
Authors: Cruz-e-Silva Victor
Published: September 2024

Correa Moylan Walsh (1862–1936) was a monetary economist of the early twentieth century, mostly remembered for his contributions to the theory of index numbers. Francis Ysidro Edgeworth (1845–1926) was a renowned mathematical economist, remembered as one of the great masters of the discipline. Walsh was an adamant defender of a deterministic, test approach to the theory of index numbers, whereas Edgeworth favored probabilistic approaches and thought index-number theorists should not close themselves to alternative methods. Holding contrasting views about the making of index numbers, they engaged in a fierce debate in the first half of the 1920s—a period marked by several quarrels on the subject. The main points in dispute between Walsh and Edgeworth were the existence of an ideal formula for index numbers and the use of probability in the measurement of price variations. The goal of this article is to explore this debate and its underpinnings. It is argued that the main points of contention between them relate to their conflicting perspectives on the nature of index numbers.
Empire and the Rhetoric of Total War in Zadie Smith’s White Teeth
Authors: Thompson Matthew
Published: September 2024

In reading Zadie Smith’s White Teeth (2000) this essay proposes a definition of total war that illuminates the close connection between the rhetoric of war and the rhetoric of imperialism. Building on the recent scholarly accounts of how “totality” is never truly possible, this essay sees total war not as a descriptor of reality but rather as a rhetorical strategy that categorizes entire populations as ally or enemy—a binary that both emerges from and remains in tension with the binaries structuring imperialism (white/nonwhite, civilized/savage). Total war, that is, defines colonial subjects as allies with their colonizers against white, European enemies. White Teeth explores these contradictions, this essay argues, by revisiting the binary rhetoric of the Second World War. And in challenging the relationship between imperial and wartime categories, Smith’s novel resists the tendencies of both imperial and anti-imperial forms of history to represent the past in terms of just such totalizing categories. As historical fiction, White Teeth counters this totalizing tendency and, dwelling instead in ambiguity and uncertainty, suggests that a truly decolonial history depends not on reversing imperial categories but on rejecting them altogether.
Proportional increment of oxygen consumption, heart rate and core body temperature in the digesting Python bivittatus
Authors: Last Katja B. , Malte Hans , Rindom Emil , Guagnoni Igor N. , Wang Tobias
Published: September 2024

The Burmese python has a remarkable digestive physiology with large elevations of metabolic rate and heart rate following feeding. Here, we investigated the relationship between heart rate, oxygen consumption and core body temperature during digestion in five pythons (Python bivittatus) by implantation of data loggers. The snakes were placed in respirometers at 30±0.1°C for 26 days and voluntarily ingested three meals of different size, whilst heart rate, core body temperature and oxygen consumption rate were measured continuously. Both oxygen consumption and heart rate increased severalfold during digestion, and metabolic heat production increased core body temperature by 2°C, explaining 12% of the observed tachycardia. The rise in core body temperature means that standard metabolic rate increased during digestion, and we estimate that failure to account for core body temperature leads to a 4% overestimation of the specific dynamic action (SDA) response. Our study reveals a close correlation between oxygen consumption and heart rate during digestion, further supporting the use of heart rate as a proxy for metabolism.