bluuebunny/crossref_metadata_2025 huggingface dataset:
Diabetes Technology Meeting 2023
Authors: Tian Tiffany , Aaron Rachel E. , DuNova Ashley Y. , Jendle Johan H. , Kerr David , Cengiz Eda , Drincic Andjela , Pickup John C. , Chen Kong Y. , Schwartz Naomi , Muchmore Douglas B. , Akturk Halis K. , Levy Carol J. , Schmidt Signe , Bellazzi Riccardo , Wu Alan H. B. , Spanakis Elias K. , Najafi Bijan , Chase James Geoffrey , Seley Jane Jeffrie , Klonoff David C.
Published: March 2024

Diabetes Technology Society hosted its annual Diabetes Technology Meeting from November 1 to November 4, 2023. Meeting topics included digital health; metrics of glycemia; the integration of glucose and insulin data into the electronic health record; technologies for insulin pumps, blood glucose monitors, and continuous glucose monitors; diabetes drugs and analytes; skin physiology; regulation of diabetes devices and drugs; and data science, artificial intelligence, and machine learning. A live demonstration of a personalized carbohydrate dispenser for people with diabetes was presented.
Guardians of data: TruMe Life’s continuous quest for data protection
Authors: Januarita Ratna , Alamsyah Indra Fajar , Perdana Arif
Published: March 2024

Over the past decade, Indonesia has witnessed a surge in data breaches, raising questions about its data-protection approach. Notable breaches include those in the health, energy, utility, e-commerce, and financial sectors. Recognising this precarious situation, the government passed Law No. 27 of 2022 on Personal Data Protection (UU PDP) in 2022, emphasising individual data rights and promoting accountability among data controllers. This case study describes the data governance, focussing on the Indonesian insurance firm, TruMe Life (pseudonymised), which adheres to international standards and Indonesia’s UU PDP. This case underscores the criticality of robust data governance in ensuring compliance and operational efficiency and bolstering customer trust in insurance, culminating in implications for research and industry practices.
Outbreak of glossitis in a boarding school, diagnostic challenges and the outcome after treatment with Vitamin B Complex tablets: A retrospective descriptive study
Authors: Nepal Tej Nath , Gyaltshen Dhendup
Published: March 2024

Objectives:

The study aimed to understand the cause of glossitis that occurred among boarding students in a central school in Chhukha, Bhutan, and the outcome after 15 days of treatment with a vitamin B complex tablet.

Methods:

The researcher extracted data from the treatment records of patients treated for glossitis from 30 September 2020 to 30 October 2020 at the boarding school and conducted a retrospective descriptive study. A total of 97 records were used in the study: the age, gender,date of reporting to school, treatment, dietary preferences, and outcome of treatment.

Results:

In all, 63 (64.9%) patients were females. The students who were staying in the hostel for longer duration were more in proportion among the patients. About 80% of the patients had subjective improvement after treatment with two doses of one tablet of vitamin B complex tablet for 15 days. There were no deaths.

Conclusion:

The study could not ascertain the definite cause of glossitis among boarding students but 80 % of the patients showed subjective improvement after treatment with daily two doses of 32.5 mg of vitamin B complex tablet. The study recommends a prospective study to understand the cause of glossitis among boarding students to prevent similar future outbreaks.
Responding to unusual government request for user data: How tech companies make sense of human rights
Authors: Ebert Isabel
Published: March 2024

Data sharing practices between governments and the private sector are characterized by a lack of transparency which has potential implications for human rights. Minimal scholarship exists investigating how companies address human rights risks stemming from government requests for user data. Understanding corporate response processes to government requests is central to advancing human rights research at the intersection of tech company conduct. This becomes even more pressing as emerging technologies gather increasing amounts of data. Scholarship demonstrates that transparency reporting cannot assist in analyzing data sharing practices between the private and the public sectors due to a variety of constraints. Using semi-structured interviews with senior staff at technology companies, this paper presents an empirical analysis of how technology company representatives and external advisors seek to align their processes when responding to government requests for user data. It describes a set of six themes using human rights terminology which company representatives aim to employ when responding to requests.
The Case of Hazel Hollow Lodge; Focusing on Employee Recruitment and Retention
Authors: Deale Cynthia S. , Lee Seung-Hyun
Published: March 2024

This case describes the employment situation at an inn in the mountains of North Carolina in the United States. The inn used to do well at recruiting and retaining employees, but recently it has had issues regarding the recruitment, training and development, satisfaction, and retention of its labor force, particularly with the onset of the COVID-19 pandemic. The dilemma is that while the inn needs to recruit and retain employees to keep operating effectively, no one on the staff has the time or ability to address the labor issues and therefore, a consultant has been invited to address the issues to try to identify possible solutions to the current and persistent challenge of attracting and retaining qualified people to work at the inn.
Enhancing Financial Security and Energy Efficiency: Integrating Biometric Payments with Power System Engineering in India
Authors: A. Jolin Daisy Rethnapriya , Ponrani D.
Published: March 2024

This research explores the integration of biometric payment systems with power system engineering within the Indian financial sector. It aims to understand and optimize this convergence by examining the current state, assessing power consumption patterns, evaluating regulatory compliance, and providing holistic insights. Utilizing a mixed-method approach including qualitative interviews, focus group discussions, and quantitative surveys, the study uncovers variations in biometric adoption rates among financial institutions, highlighting the correlation with power consumption and the necessity for standardized frameworks. The findings underscore the importance of balancing technology adoption, energy efficiency, and data protection. Practical implications include informed decision-making for financial institutions and refined policies for regulatory authorities to foster a secure, efficient, and sustainable payment ecosystem. This research contributes to existing knowledge by offering comprehensive insights and emphasizes the need for energy-efficient strategies and robust regulatory standards. Overall, it advances our understanding of this convergence, paving the way for a more secure and sustainable financial technology landscape in India.
Etiologic subtypes of first and recurrent ischemic stroke in young patients using A-S-C-O and TOAST classification criteria: A retrospective follow-up study
Authors: Aarnio Karoliina , Martinez-Majander Nicolas , Haapaniemi Elena , Kokkola Eeva , Broman Jenna , Tulkki Lauri , Kaste Markku , Tatlisumak Turgut , Putaala Jukka
Published: March 2024

Introduction:

Scarce data exist on the etiology of recurrent ischemic strokes (ISs) among young adults. We analyzed the etiology of first-ever and recurrent events and the differences between them.

Patients and methods:

Patients aged 15–49 years with a first-ever IS in 1994–2007 were included in the Helsinki Young Stroke Registry. In this retrospective cohort study, data on recurrent ISs were identified from Care Register for Health Care until the end of 2017 and Causes of Death Register and from patient records until the end of 2020. All first-ever and recurrent ISs were classified using Atherosclerosis-Small vessel disease-Cardioembolism-Other Cause (A-S-C-O) and Trial of Org 10172 in Acute Stroke Treatment (TOAST) classifications.

Results:

A total of 970 patients were included (median age at index IS 46 years, interquartile range 43–48, 33% women), of which 155 (16.0%) patients had recurrent IS, with 8 (5.2%) fatal cases and 5 (3.2%) unverifiable cases. The median follow-up was 17.4 (IQR 13.9–21.7) years. Median time from the index event to the first recurrent event was 4.5 (interquartile range [IQR] 1.6–10.2) years. Recurrence was more often due to definite cardioembolism (10.7% vs 18.0%, p = 0.013), while the proportion of other definite A-S-C-O subgroups remained the same. With TOAST classification, the proportion of true cryptogenic ISs decreased (16.7% vs 6.7%, p = 0.003), while those with incomplete evaluation increased (9.3% vs 19.3%, p = 0.015). Other TOAST phenotypes remained the same.

Conclusion:

The proportion of definite cardioembolism increased at recurrence using the A-S-C-O classification and the number of cryptogenic ISs decreased using the TOAST classification, while cases with incomplete evaluation increased. Most etiologies remained the same.
Geo-visualisation of the community structure of intercity express delivery network in China based on waybill big data
Authors: Chang Jiacheng , Li Guoqi , Sun Wenjie , He Nannan , Du Guopeng
Published: March 2024

Waybill data can reflect the transport process of express delivery in different cities, providing an important basis for revealing intercity logistics connectivity. However, current research neglects the critical function of routing information in waybill data, making it difficult to realistically represent intercity connectivity in the express delivery network. This study uses waybill big data with routing information to map the spatial distribution and network structures of intercity express delivery networks in China, and identifies three main types of network communities: interprovincial communities, regional hub communities, and corridor pattern communities, so that a more accurate and realistic representation of intercity connectivity can be presented.
Investigation of the morphological, physiological, biochemical, and catabolic characteristics and gene expression under drought stress in tolerant and sensitive genotypes of wild barley [Hordeum vulgare subsp. spontaneum (K. Koch) Asch. & Graebn.]
Authors: Shirvani Hooman , Mehrabi Ali Ashraf , Farshadfar Mohsen , Safari Hooshmand , Arminian Ali , Fatehi Foad , Pouraboughadareh Alireza , Poczai Peter
Published: March 2024

Background

Barley (H. vulgare L.) is an important cereal crop cultivated across various climates globally. Barley and its ancestor (H. vulgare subsp. spontaneum) are an economically valuable model for genetic research and improvement. Drought, among various abiotic stresses, is a substantial threat to agriculture due to its unpredictable nature and significant impact on crop yield.

Results

This study was conducted in both greenhouse and laboratory settings. Prior to the study, wild barley accessions were pre-selected based on their sensitivity or tolerance to drought as determined from fieldwork in the 2020–2021 and 2021–2022 cropping seasons. The effects of three levels of drought stress were evaluated (control, 90–95% field capacity [FC]; mild stress, 50–55% FC; and severe stress, 25–30% FC). Several parameters were assessed, including seedling and root growth, enzymatic activity (CAT, SOD, POD), soluble protein levels, chlorophyll content, carotenoids, abaxial and adaxial stomatal density and dimensions, and relative gene expression of Dhn1, SOD, POD, and CAT. Drought stress significantly increased enzyme activities, especially at 25–30% FC, and more in the tolerant genotype. On the other hand, sensitive genotypes showed a notable increase in stomatal density. Under drought stress, there was a general decline in seedling and root growth, protein content, chlorophyll and carotenoids, and stomatal dimensions. Importantly, gene expression analysis revealed that Dhn1, SOD, POD, and CAT were upregulated under drought, with the highest expression levels observed in the drought-tolerant genotype under severe stress conditions (25–30% FC).

Conclusions

Our investigation highlights the distinct morphological, physiological, biochemical, and gene-expression profiles of drought-resistant and drought-sensitive wild barley genotypes under varying degrees of drought.
Effect of pretreatment with a small dose of esketamine on sufentanil-induced cough during anesthesia induction: a randomized controlled trial
Authors: Gao Liangliang , Zhang Zhuoliang , Zhu Yi , Lu Xinyu , Tian Yue , Wei Lei
Published: March 2024

Background

Sufentanil-induced cough is common during the induction of anesthesia. The objective of this study was to determine whether pretreatment with a small dose of esketamine is effective in treating sufentanil-induced cough.

Methods

220 patients were screened, and 200 patients who had scheduled elective surgery and were between 18 and 70 years old were randomly divided into two groups. Before sufentanil was administered, esketamine group (group K) was injected with 0.15 mg/kg esketamine at 5 s, and control group (group C) was administered with the same volume. Within 1 min after sufentanil(0.4ug/kg) injection during induction, cough incidence and severity were evaluated. After sufentanil was injected, we recorded its hemodynamic changes and side effects.

Results

In the esketamine group (group K) and control group (group C), there was an incidence of cough of 5 and 34%, respectively. The esketamine group (group K) had a significantly lower incidence and severity of cough compared to the control group (group C) immediately after sufentanil injection (P < 0.05). MAP and HR did not differ significantly between the two groups during three different times of general anesthesia induction (P > 0.05).

Conclusion

In our study, we found that sufentanil-induced cough was significantly reduced by pretreatment with 0.15 mg/kg esketamine, but with no significant changes in the hemodynamic status.

Trial registration

Chinese Clinical Trial Registry (ChiCTR2200063821, registered date: 17/09/2022), http://www.chictr.org.cn
Socio-environmental predictors of diabetes incidence disparities in Tanzania mainland: a comparison of regression models for count data
Authors: Mbwambo Sauda Hatibu , Mbago Maurice C. , Rao Gadde Srinivasa
Published: March 2024

Background

Diabetes is one of the top four non-communicable diseases that cause death and illness to many people around the world. This study aims to use an efficient count data model to estimate socio-environmental factors associated with diabetes incidences in Tanzania mainland, addressing lack of evidence on the efficient count data model for estimating factors associated with disease incidences disparities.

Methods

This study analyzed diabetes counts in 184 Tanzania mainland councils collected in 2020. The study applied generalized Poisson, negative binomial, and Poisson count data models and evaluated their adequacy using information criteria and Pearson chi-square values.

Results

The data were over-dispersed, as evidenced by the mean and variance values and the positively skewed histograms. The results revealed uneven distribution of diabetes incidence across geographical locations, with northern and urban councils having more cases. Factors like population, GDP, and hospital numbers were associated with diabetes counts. The GP model performed better than NB and Poisson models.

Conclusion

The occurrence of diabetes can be attributed to geographical locations. To address this public health issue, environmental interventions can be implemented. Additionally, the generalized Poisson model is an effective tool for analyzing health information system count data across different population subgroups.
Impact of resistance exercise on patients with chronic kidney disease
Authors: Chen Chong-Cheng , Huang Yue-Yang , Hua-Zhang  , Xia-Liu  , Li Xue-Qin , Long Yan-Qiong , Chen Zheng-Wen , Jin Tao
Published: March 2024

Background

Chronic kidney disease (CKD) has become an increasingly important public health disease with a high incidence rate and mortality. Although several studies have explored the effectiveness of resistance exercise in improving the prognosis of CKD patients, the number of studies is still limited and the results are still controversial.

Objectives

We conducted this meta-analysis of randomized controlled trials (RCT) studies to evaluate the effectiveness of resistance exercise on CKD patients.

Methods

The PubMed, Embase, and Cochrane Library databases were searched from the inception date to October 2023. The meta-analysis was conducted to evaluate 12 main indicators, including glomerular filtration rate (GFR)(ml/(min•1.73m2)), C-reactive protein (CRP) (mg/L), serum creatinine (mg/dL), hemoglobin (g/dL), Glycosylated Hemoglobin, Type A1C (HBA1c) (%), high Density Lipoprotein (HDL) (mg/dL), low Density Lipoprotein (LDL) (mg/dL), 6-min walk(m), body mass index (BMI) (kg/m2), fat-free mass (kg), fat mass (kg), grip strength (kgf).

Results

Sixteen RCT studies were included in this meta-analysis from 875 records. GFR exhibited no significant change in CKD patients treated with resistance exercise (WMD 1.82; 95%CI -0.59 to 4.23;P = 0.139). However, 6-min walk (WMD 89.93; 95%CI 50.12 to 129.74;P = 0.000), fat-free mass (WMD 6.53; 95%CI 1.14 to 11.93;P = 0.018) and grip strength (WMD 3.97; 95%CI 1.89 to 6.05;P = 0.000) were significantly improved with resistance exercise. The level of CRP (WMD − 2.46; 95%CI -4.21 to -0.72;P = 0.006) and HBA1c (WMD − 0.46; 95%CI -0.63 to -0.29;P = 0.000) dropped significantly after resistance exercise treatment.

Conclusions

Resistance exercise can improve physical function, metabolic condition, inflammatory response and cardiopulmonary function in CKD patients, specifically reflected in the increase of indicators fat-free mass, grip strength, 6-min walk, as well as the decrease of indicators HBA1c and CRP.
Immature central tumor tertiary lymphoid structures are associated with better prognosis in non-small cell lung cancer
Authors: Xiaoxu Deng , Min Xu , Chengcheng Cao
Published: March 2024

Background & aims

Tertiary lymphoid structures (TLSs) are predictive biomarkers of favorable clinical outcomes and immunotherapy response in several solid malignancies, including non-small cell lung cancer (NSCLC). However, the relationship between TLSs and NSCLC prognosis has not been eludicated from the aspects of location, density, and maturity. This study aimed to investigate the clinicopathological and prognostic significance of TLSs in NSCLC.

Methods

A collection of 151 resected pulmonary nodules in patients with NSCLC was retrospectively analyzed. Two experienced pathologists reviewed hematoxylin-eosin (H&E) slides and assessed TLS scores at different anatomic subregions. Then, we analyzed their correlation with clinicopathologic parameters and CD8 staining intensity and assessed multiple clinicopathological factors affecting patient prognosis.

Results

CD8 expression was correlated with total (TLS-CT) (P = 0.000), aggregates (Agg) (TLS-CT) (P = 0.001), follicles (FOL)-I (TLS-CT) (P = 0.025), and TLS(overall) (P = 0.013). TLS scores in the central tumor (CT) and invasion margin (IM) areas were negatively correlated with distant metastasis and Union for International Cancer Control (UICC) stage in NSCLC patients, while TLS score in the CT area was positively correlated with CD8 expression. TLS (overall), Agg (TLS-CT), and FOL-I (TLS-CT) were positively correlated with distant metastasis, UICC stage, and CD8 expression in NSCLC patients. Agg (TLS-IM) was positively correlated with distant metastasis and UICC stage. FOL-I (TLS-IM) was positively correlated with UICC stage. FOL-II (TLS-IM) was positively correlated with distant metastasis (P < 0.05). Multivariate Cox regression analysis showed that unfavorable independent prognostic factors were associated with metastasis status and UICC stage. Independent prognostic factors with protective effects included Agg (TLS-CT), FOL-I (TLS-CT), total (TLS-CT), and overall TLS (P < 0.05).

Conclusion

Histological score assessment of H&E sections of Agg (TLS-CT), FOL-I (TLS-CT), total (TLS-CT), and overall TLS levels in NSCLC has prognostic value.
The effect of hydrogen-rich water consumption on premenstrual symptoms and quality of life: a randomized controlled trial
Authors: Aker Menekşe Nazlı , Gönenç İlknur M. , Çalişici Dilan , Bulut Menekşe , Alwazeer Duried , LeBaron Tyler W.
Published: March 2024

Background

Premenstrual syndrome (PMS) consists of psychiatric or somatic symptoms negatively affecting the daily life. PMS treatment can involve the use of complementary-alternative approaches. Hydrogen-rich water (HRW) has antioxidant and anti-inflammatory properties that may treat PMS. This study aimed to investigate the effect of drinking HRW on the severity of premenstrual symptoms and the quality of life of women who suffer from PMS.

Methods

This study is a randomized controlled trial. Participants were randomized into two groups (intervention group=33, control group=32) using the block randomization method. Participants were requested to consume 1500-2000 mL of HRW daily in the intervention group and drink water in the placebo group. Participants began drinking either HRW or placebo water from day 16 of their menstrual cycle until day 2 of the following cycle for three menstrual cycles. The research data were collected using a Demographic Information Form, Premenstrual Syndrome Scale (PMSS), and Short form of the World Health Organization Quality of Life Questionnaire (WHOQOL- BREF).

Results

The intervention group had significantly lower mean scores than the control group in both the first and second follow-ups on the PMSS (P<0.05). In the first follow-up, the intervention group had significantly higher mean scores in the Physical Health and Psychological domains of the WHOQOL-BREF compared to the control group (P<0.05). Group × time interaction was significant for PMSS (F = 10.54,P<0.001). Group × time interaction was insignificant for WHOQOL- BREF (P>0.05).

Conclusions

The consumption of HRW reduces the severity of premenstrual symptoms and improves individuals' quality of life in physical and psychological domains.
RAF inhibitor re-challenge therapy in BRAF-aberrant pan-cancers: the RE-RAFFLE study
Authors: Nelson Blessie Elizabeth , Roszik Jason , Ahmed Jibran , Barretto Carmelia Maria Noia , Nardo Mirella , Campbell Erick , Johnson Amber M , Piha-Paul Sarina A. , Oliva Isabella C. Glitza , Weathers Shiao-Pei , Cabanillas Maria , Javle Milind , Meric-Bernstam Funda , Subbiah Vivek
Published: March 2024

Previous studies have shown the clinical benefit of rechallenging the RAF pathway in melanoma patients previously treated with BRAF inhibitors. 44 patients with multiple tumors harboring RAF alterations were rechallenged with a second RAF inhibitor, either as monotherapy or in combination with other therapies, after prior therapy with a first RAF inhibitor. This retrospective observational study results showed that rechallenging with RAFi(s) led to an overall response rate of 18.1% [PR in thyroid (1 anaplastic; 3 papillary), 1 ovarian, 2 melanoma, 1 cholangiocarcinoma, and 1 anaplastic astrocytoma]. The clinical benefit rate was 54.5%; more than 30% of patients had durable responses with PR and SD lasting > 6 months. The median progression-free survival on therapy with second RAF inhibitor in the rechallenge setting either as monotherapy or combination was shorter at 2.7 months (0.9-30.1 m) compared to 8.6 months (6.5-11.5 m) with RAF-1i. However, the median PFS with RAF-2i responders (PFS-2) improved at 12.8 months compared to 11.4 months with RAF-1i responders. The median OS from retreatment with RAF-2i was 15.5 months (11.1-30.8 m). Further prospective studies are needed to validate these results and expand targeted therapy options for RAF-aberrant cancers.
A new role for spinal manual therapy and for chiropractic? Part I: weaknesses and threats
Authors: O’Neill Søren Francis Dyhrberg , Nim Casper , Newell Dave , Leboeuf-Yde Charlotte
Published: March 2024

Spinal manual therapy is central to chiropractic history, clinical practice, and professional identity. That chiropractors have developed an expertise in this domain has provided some considerable advantages. However, we contend it is also at the crux of the ideological schism that fractures the chiropractic profession. In this article, which is the first in a series of two, we discuss chiropractors’ understanding and use of spinal manual therapy and do so with particular emphasis on what we see as weaknesses it creates and threats it gives rise to. These are of particular importance, as we believe they have limited the chiropractic profession’s development. As we shall argue, we believe that these threats have become existential in nature, and we are convinced that they call for a resolute and unified response by the profession. Subsequently, in part II, we discuss various strengths that the chiropractic profession possesses and the opportunities that await, provided that the profession is ready to rise to the challenge.
Newly designed plate for the treatment of posterolateral tibial plateau fractures: a finite element analysis
Authors: Yan Zhaokui , Zou Chang , Kenmegne Guy Romeo , Pan Xuelin , Ghimire Nawin , Silva Kuruwitage Manthi Nihara , Fang Yue
Published: March 2024

Background

This study investigated the biomechanical properties of a new plate used for the treatment of posterolateral tibial plateau fractures using finite element analysis.

Methods

The study groups were as follows: group PM, model of the new plate with posteromedial tibial plateau fracture; group PL, model of the new plate with posterolateral tibial plateau fracture; and group PC, model of the new plate with posterior tibial plateau fracture. We used two loading modes: uniform loading on the entire plateau, and loading on the posterior plateau. Data such as the displacement of the fracture and distribution of stress on the new plate and screws were recorded and analyzed.

Results

When the whole plateau was loaded, the displacement of fractures in groups PM, PL, and PC were 0.273, 0.114, and 0.265 mm, respectively. The maximum stresses on the plates in groups PM, PL, and PC were 118.131 MPa, 44.191 MPa, and 115.433 MPa. The maximum stresses on the screws in Groups PM, PL, and PC were 166.731, 80.330, and 164.439 MPa, respectively. When the posterior tibial plateau was loaded, the displacement of the fractures in groups PM, PL, and PC was 0.410, 0.213, and 0.390 mm, respectively. The maximum stresses on the plates in groups PM, PL, and PC were 194.012 MPa, 72.806 MPa, and 185.535 MPa. The maximum stresses on the screws in Groups PM, PL, and PC were 278.265, 114.839, and 266.396 MPa, respectively.

Conclusion

The results of this study revealed that titanium plates have good fixation effects in all groups; therefore, the use of the new plate for posterolateral tibial plateau fractures appears to be safe and valid.
Bispecific aptamer-decorated and light-triggered nanoparticles targeting tumor and stromal cells in breast cancer derived organoids: implications for precision phototherapies
Authors: Camorani Simona , Caliendo Alessandra , Morrone Elena , Agnello Lisa , Martini Matteo , Cantile Monica , Cerrone Margherita , Zannetti Antonella , La Deda Massimo , Fedele Monica , Ricciardi Loredana , Cerchia Laura
Published: March 2024

Background

Based on the established role of cancer-stroma cross-talk in tumor growth, progression and chemoresistance, targeting interactions between tumor cells and their stroma provides new therapeutic approaches. Dual-targeted nanotherapeutics selectively acting on both tumor and stromal cells may overcome the limits of tumor cell-targeting single-ligand nanomedicine due to the complexity of the tumor microenvironment.

Methods

Gold-core/silica-shell nanoparticles embedding a water-soluble iridium(III) complex as photosensitizer and luminescent probe (Iren-AuSiO2_COOH) were efficiently decorated with amino-terminated EGFR (CL4) and PDGFRβ (Gint4.T) aptamers (Iren-AuSiO2_Aptamer). The targeting specificity, and the synergistic photodynamic and photothermal effects of either single- and dual-aptamer-decorated nanoparticles have been assessed by confocal microscopy and cell viability assays, respectively, on different human cell types including mesenchymal subtype triple-negative breast cancer (MES-TNBC) MDA-MB-231 and BT-549 cell lines (both EGFR and PDGFRβ positive), luminal/HER2-positive breast cancer BT-474 and epidermoid carcinoma A431 cells (only EGFR positive) and adipose-derived mesenchymal stromal/stem cells (MSCs) (only PDGFRβ positive). Cells lacking expression of both receptors were used as negative controls. To take into account the tumor-stroma interplay, fluorescence imaging and cytotoxicity were evaluated in preclinical three-dimensional (3D) stroma-rich breast cancer models.

Results

We show efficient capability of Iren-AuSiO2_Aptamer nanoplatforms to selectively enter into target cells, and kill them, through EGFR and/or PDGFRβ recognition. Importantly, by targeting EGFR+ tumor/PDGFRβ+ stromal cells in the entire tumor bulk, the dual-aptamer-engineered nanoparticles resulted more effective than unconjugated or single-aptamer-conjugated nanoparticles in either 3D spheroids cocultures of tumor cells and MSCs, and in breast cancer organoids derived from pathologically and molecularly well-characterized tumors.

Conclusions

Our study proposes smart, novel and safe multifunctional nanoplatforms simultaneously addressing cancer-stroma within the tumor microenvironment, which are: (i) actively delivered to the targeted cells through highly specific aptamers; (ii) localized by means of their luminescence, and (iii) activated via minimally invasive light, launching efficient tumor death, thus providing innovative precision therapeutics. Given the unique features, the proposed dual targeted nanoformulations may open a new door to precision cancer treatment.
ANU-ADRI scores, tau pathology, and cognition in non-demented adults: the CABLE study
Authors: Yin Shan , Gao Pei-Yang , Ou Ya-Nan , Fu Yan , Liu Ying , Wang Zuo-Teng , Han Bao-Lin , Tan Lan
Published: March 2024

Background

It has been reported that the risk of Alzheimer’s disease (AD) could be predicted by the Australian National University Alzheimer Disease Risk Index (ANU-ADRI) scores. However, among non-demented Chinese adults, the correlations of ANU-ADRI scores with cerebrospinal fluid (CSF) core biomarkers and cognition remain unclear.

Methods

Individuals from the Chinese Alzheimer’s Biomarker and LifestyLE (CABLE) study were grouped into three groups (low/intermediate/high risk groups) based on their ANU-ADRI scores. The multiple linear regression models were conducted to investigate the correlations of ANU-ADRI scores with several biomarkers of AD pathology. Mediation model and structural equation model (SEM) were conducted to investigate the mediators of the correlation between ANU-ADRI scores and cognition.

Results

A total of 1078 non-demented elders were included in our study, with a mean age of 62.58 (standard deviation [SD] 10.06) years as well as a female proportion of 44.16% (n = 476). ANU-ADRI scores were found to be significantly related with MMSE (β = -0.264, P < 0.001) and MoCA (β = -0.393, P < 0.001), as well as CSF t-tau (β = 0.236, P < 0.001), p-tau (β = 0.183, P < 0.001), and t-tau/Aβ42 (β = 0.094, P = 0.005). Mediation analyses indicated that the relationships of ANU-ADRI scores with cognitive scores were mediated by CSF t-tau or p-tau (mediating proportions ranging from 4.45% to 10.50%). SEM did not reveal that ANU-ADRI scores affected cognition by tau-related pathology and level of CSF soluble triggering receptor expressed on myeloid cells 2 (sTREM2).

Conclusion

ANU-ADRI scores were associated with cognition and tau pathology. We also revealed a potential pathological mechanism underlying the impact of ANU-ADRI scores on cognition.
Radiology domain in the diagnosis of IgG4-RD according to the 2019 American College of Rheumatology and European League Against Rheumatism classification
Authors: Elbanna Khaled Y. , Kowa Jie-Ying , Mirajkar Nikhil , Khalili Korosh , Kim Tae Kyoung
Published: March 2024

Objectives

To evaluate the performance of radiology-related inclusion criteria of the 2019 ACR-EULAR classification system in the diagnosis of IgG4-related disease (IgG4-RD).

Methods

This retrospective single-institution study included patients who received a diagnosis of IgG4-RD between January 2010 and December 2020. Two abdominal radiologists independently reviewed baseline imaging studies and scored radiology findings according to the 2019 ACR-EULAR classification criteria. Additional scores were assigned based on serological, histopathological, and immunostaining features.

Results

Seventy-four patients (58 males and 16 females) with a mean age of 59.3 ± 13.9 years diagnosed with IgG4-RD were included. 51/74 (68.9%) were classified as having IgG4-RD according to the 2019 ACR-EULAR classification criteria. To reach a score ≥ 20 in these 51 patients, the radiology domain was sufficient in 20/51 (39.2%) and adding the serology domain was required for another 20/51 (39.2%). The remaining 11/51 patients (21.6%) required the histopathology and immunostaining domains. Radiological involvement of two or more organs at presentation was significantly associated with a score of ≥ 20 and seen in 43/51 (84.3%) compared to 5/23 (21.7%) of the non-classified group (p < 0.001). The group classified as having IgG4-RD showed a significantly higher proportion of elevated IgG4 levels (39/51, 76.5%) than the non-classified group (8/23, 34.8%) (< 0.001).

Conclusion

The study findings support the effectiveness of the radiology-related inclusion criteria of the 2019 ACR-EULAR classification system in diagnosing IgG4-RD. Combining radiology and serology domains achieved the cut-off in 80% of IgG-RD patients, enabling non-invasive diagnosis. The classification of IgG4-RD was significantly associated with multi-organ involvement, particularly affecting the pancreas and biliary system.

Critical relevance statement

This study is the first to evaluate the diagnostic performance of the radiology domain in the 2019 ACR-EULAR classification criteria. The study results confirm its utility and potential to enable non-invasive diagnosis when combined with serological testing in a significant proportion of patients.

Key points

• A significant proportion of patients can be diagnosed with IgG4-RD using the radiology and serology domains exclusively.

• Multi-organ involvement is significantly associated with classifying patients as IgG4-RD, with the pancreas and biliary system most frequently affected.

• A high level of inter-reader agreement in the scoring of the radiology domain supports its reliability.

Graphical Abstract
Predicting microvascular invasion in small (≤ 5 cm) hepatocellular carcinomas using radiomics-based peritumoral analysis
Authors: Wang Fang , Cheng Ming , Du Binbin , Li Jing , Li Liming , Huang Wenpeng , Gao Jianbo
Published: March 2024

Objective

We assessed the predictive capacity of computed tomography (CT)-enhanced radiomics models in determining microvascular invasion (MVI) for isolated hepatocellular carcinoma (HCC) ≤ 5 cm within peritumoral margins of 5 and 10 mm.

Methods

Radiomics software was used for feature extraction. We used the least absolute shrinkage and selection operator (LASSO) algorithm to establish an effective model to predict patients’ preoperative MVI status.

Results

The area under the curve (AUC) values in the validation sets for the 5- and 10-mm radiomics models concerning arterial tumors were 0.759 and 0.637, respectively. In the portal vein phase, they were 0.626 and 0.693, respectively. Additionally, the combined radiomics model for arterial tumors and the peritumoral 5-mm margin had an AUC value of 0.820. The decision curve showed that the combined tumor and peritumoral radiomics model exhibited a somewhat superior benefit compared to the traditional model, while the fusion model demonstrated an even greater advantage, indicating its significant potential in clinical application.

Conclusion

The 5-mm peritumoral arterial model had superior accuracy and sensitivity in predicting MVI. Moreover, the combined tumor and peritumoral radiomics model outperformed both the individual tumor and peritumoral radiomics models. The most effective combination was the arterial phase tumor and peritumor 5-mm margin combination. Using a fusion model that integrates tumor and peritumoral radiomics and clinical data can aid in the preoperative diagnosis of the MVI of isolated HCC ≤ 5 cm, indicating considerable practical value.

Critical relevance statement

The radiomics model including a 5-mm peritumoral expansion is a promising noninvasive biomarker for preoperatively predicting microvascular invasion in patients diagnosed with a solitary HCC ≤ 5 cm.

Key points

• Radiomics features extracted at a 5-mm distance from the tumor could better predict hepatocellular carcinoma microvascular invasion.

• Peritumoral radiomics can be used to capture tumor heterogeneity and predict microvascular invasion.

• This radiomics model stands as a promising noninvasive biomarker for preoperatively predicting MVI in individuals.

Graphical Abstract
Sex and statin-related genetic associations at the PCSK9 gene locus: results of genome-wide association meta-analysis
Authors: Pott Janne , Kheirkhah Azin , Gadin Jesper R. , Kleber Marcus E. , Delgado Graciela E. , Kirsten Holger , Forer Lukas , Hauck Stefanie M. , Burkhardt Ralph , Scharnagl Hubert , Loeffler Markus , März Winfried , Thiery Joachim , Gieger Christian , Peters Annette , Silveira Angela , Hooft Ferdinand van’t , Kronenberg Florian , Scholz Markus
Published: March 2024

Background

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key player of lipid metabolism with higher plasma levels in women throughout their life. Statin treatment affects PCSK9 levels also showing evidence of sex-differential effects. It remains unclear whether these differences can be explained by genetics.

Methods

We performed genome-wide association meta-analyses (GWAS) of PCSK9 levels stratified for sex and statin treatment in six independent studies of Europeans (8936 women/11,080 men respectively 14,825 statin-free/5191 statin-treated individuals). Loci associated in one of the strata were tested for statin- and sex-interactions considering all independent signals per locus. Independent variants at the PCSK9 gene locus were then used in a stratified Mendelian Randomization analysis (cis-MR) of PCSK9 effects on low-density lipoprotein cholesterol (LDL-C) levels to detect differences of causal effects between the subgroups.

Results

We identified 11 loci associated with PCSK9 in at least one stratified subgroup (p < 1.0 × 10–6), including the PCSK9 gene locus and five other lipid loci: APOB, TM6SF2, FADS1/FADS2, JMJD1C, and HP/HPR. The interaction analysis revealed eight loci with sex- and/or statin-interactions. At the PCSK9 gene locus, there were four independent signals, one with a significant sex-interaction showing stronger effects in men (rs693668). Regarding statin treatment, there were two significant interactions in PCSK9 missense mutations: rs11591147 had stronger effects in statin-free individuals, and rs11583680 had stronger effects in statin-treated individuals. Besides replicating known loci, we detected two novel genome-wide significant associations: one for statin-treated individuals at 6q11.1 (within KHDRBS2) and one for males at 12q24.22 (near KSR2/NOS1), both with significant interactions. In the MR of PCSK9 on LDL-C, we observed significant causal estimates within all subgroups, but significantly stronger causal effects in statin-free subjects compared to statin-treated individuals.

Conclusions

We performed the first double-stratified GWAS of PCSK9 levels and identified multiple biologically plausible loci with genetic interaction effects. Our results indicate that the observed sexual dimorphism of PCSK9 and its statin-related interactions have a genetic basis. Significant differences in the causal relationship between PCSK9 and LDL-C suggest sex-specific dosages of PCSK9 inhibitors.
Barriers and enablers to the implementation of patient-reported outcome and experience measures (PROMs/PREMs): protocol for an umbrella review
Authors: Fontaine Guillaume , Poitras Marie-Eve , Sasseville Maxime , Pomey Marie-Pascale , Ouellet Jérôme , Brahim Lydia Ould , Wasserman Sydney , Bergeron Frédéric , Lambert Sylvie D.
Published: March 2024

Background

Patient-reported outcome and experience measures (PROMs and PREMs, respectively) are evidence-based, standardized questionnaires that can be used to capture patients’ perspectives of their health and health care. While substantial investments have been made in the implementation of PROMs and PREMs, their use remains fragmented and limited in many settings. Analysis of multi-level barriers and enablers to the implementation of PROMs and PREMs has been hampered by the lack of use of state-of-the-art implementation science frameworks. This umbrella review aims to consolidate available evidence from existing quantitative, qualitative, and mixed-methods systematic and scoping reviews covering factors that influence the implementation of PROMs and PREMs in healthcare settings.

Methods

An umbrella review of systematic and scoping reviews will be conducted following the guidelines of the Joanna Briggs Institute (JBI). Qualitative, quantitative, and mixed methods reviews of studies focusing on the implementation of PROMs and/or PREMs in all healthcare settings will be considered for inclusion. Eight bibliographical databases will be searched. All review steps will be conducted by two reviewers independently. Included reviews will be appraised and data will be extracted in four steps: (1) assessing the methodological quality of reviews using the JBI Critical Appraisal Checklist; (2) extracting data from included reviews; (3) theory-based coding of barriers and enablers using the Consolidated Framework for Implementation Research (CFIR) 2.0; and (4) identifying the barriers and enablers best supported by reviews using the Grading of Recommendations Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual) approach. Findings will be presented in diagrammatic and tabular forms in a manner that aligns with the objective and scope of this umbrella review, along with a narrative summary.

Discussion

This umbrella review of quantitative, qualitative, and mixed-methods systematic and scoping reviews will inform policymakers, researchers, managers, and clinicians regarding which factors hamper or enable the adoption and sustained use of PROMs and PREMs in healthcare settings, and the level of confidence in the evidence supporting these factors. Findings will orient the selection and adaptation of implementation strategies tailored to the factors identified.

Systematic review registration

PROSPERO CRD42023421845.
On an m-dimensional system of quantum inclusions by a new computational approach and heatmap
Authors: Ghaderi Mehran , Rezapour Shahram
Published: March 2024

Recent research indicates the need for improved models of physical phenomena with multiple shocks. One of the newest methods is to use differential inclusions instead of differential equations. In this work, we intend to investigate the existence of solutions for an m-dimensional system of quantum differential inclusions. To ensure the existence of the solution of inclusions, researchers typically rely on the Arzela–Ascoli and Nadler’s fixed point theorems. However, we have taken a different approach and utilized the endpoint technique of the fixed point theory to guarantee the solution’s existence. This sets us apart from other researchers who have used different methods. For a better understanding of the issue and validation of the results, we presented numerical algorithms, tables, and some figures. The paper ends with an example.
Hospitalization is a missed opportunity for HIV screening, pre-exposure prophylaxis, and treatment
Authors: Bradford William , Akselrod Hana , Bassler John , Gagnon Kelly W. , Burkholder Greer , Carpenter Joseph Edward , Steck Alaina , Catalanotti Jillian , Kuo Irene , McGonigle Keanan , Mai William , Notis Melissa , Brokus Christopher , Kattakuzhy Sarah , Rosenthal Elana , Eaton Ellen F.
Published: March 2024

Background

Hospitalization is a “reachable moment” for people who inject drugs (PWID), but preventive care including HIV testing, prevention and treatment is rarely offered within inpatient settings.

Methods

We conducted a multisite, retrospective cohort study of patients with opioid use disorder with infectious complications of injection drug use hospitalized between 1/1/2018–12/31/2018. We evaluated HIV care continuum outcomes using descriptive statistics and hypothesis tests for intergroup differences.

Results

322 patients were included. Of 300 patients without known HIV, only 2 had a documented discussion of PrEP, while only 1 was prescribed PrEP on discharge. Among the 22 people with HIV (PWH), only 13 (59%) had a viral load collected during admission of whom all were viremic and 10 (45%) were successfully linked to care post-discharge. Rates of readmission, Medicaid or uninsured status, and unstable housing were high in both groups.

Discussion

We observed poor provision of HIV testing, PrEP and other HIV services for hospitalized PWID across multiple U.S. medical centers. Future initiatives should focus on providing this group with comprehensive HIV testing and treatment services through a status neutral approach.
Comparative analysis of anti-obesity effects of green, fermented, and γ-aminobutyric acid teas in a high-fat diet-induced mouse model
Authors: Lee Seung-Jun , Cho Kyoung Hwan , Kim Jong Cheol , Choo Ho Jin , Hwang Jeong-Yun , Cho Hyun Chin , Hah Young-Sool
Published: March 2024

Obesity, a prevalent disease associated with numerous chronic conditions, including hyperlipidemia, hyperglycemia, diabetes, and metabolic syndrome, remains a major global health challenge. This study investigated the potential of green tea (GT), fermented tea (FT), and γ-aminobutyric acid (GABA) tea (GBT), which are rich in phytonutrients and polyphenols, for the management of obesity. Using a high-fat diet-induced obese mouse model (C57BL/6N), we explored the effect of these teas on various obesity-related parameters. The mice were categorized into five groups: normal diet with water, high-fat diet with water, and high-fat diet supplemented with GT, FT, or GBT. Over 13 weeks, we monitored body weight, perirenal and liver fat, adipocyte lipid accumulation, and key metabolic indicators, such as serum cholesterol, leptin, insulin, and fasting blood glucose. These teas contain beneficial phytochemicals such as GABA, theanine, and caffeine, and have demonstrated an enhanced antioxidant capacity, which increases the scavenging of free radicals and may reduce oxidative stress. The animal study indicated a decrease in feeding efficiency and significant reductions in body weight liver fat, epididymal fat, and perirenal fat, as well as in adipocyte lipid accumulation. Additionally, notable improvements were observed in metabolic health indicators, including reductions in serum cholesterol, leptin, insulin, and fasting blood glucose levels. Our findings revealed that GT, FT, or GBT significantly counteracted the negative effects of a high-fat diet, suggesting their potential in combating obesity and related metabolic disorders.