bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical characteristics and surgical outcomes in patients with superior oblique muscle palsy: a retrospective study on 1057 patients
Authors: Masoomian Babak , Akbari Mohammad Reza , Mohammed Marrwan Hisham , Sadeghi Motahhareh , Mirmohammadsadeghi Arash , Aghsaei Fard Masoud , Khorrami-Nejad Masoud
Published: June 2024

Background

To evaluate the clinical findings of patients with SOP who underwent surgery.

Methods

This historical cohort study was performed on 1057 SOP patients managed with surgery in Farabi Hospital, Iran, from 2011 to 2022.

Results

There were 990 (93.7%) patients with unilateral SOP with the mean age of 21.8 ± 14.8 years. Of these, 715 patients (72.2%) were diagnosed with congenital SOP, and 275 patients (27.8%) had acquired SOP (P < 0.001). In contrast, 67 (6.3%) patients were diagnosed with bilateral SOP, with the mean age of 19.4 ± 15.6 years. Among these, 18 cases exhibited the masked type. The mean angle of vertical deviation in primary position at far in unilateral and bilateral cases was 15.6 ± 8.3 and 13.3 ± 9.1 △, respectively (P < 0.001). In unilateral cases, abnormal head posture (AHP) was detected in 847 (85.5%) patients and 12 (1.2%) had paradoxical AHP. Amblyopia was found in 89 (9.9%) unilateral and 7 (10.3%) bilateral cases. Solitary inferior oblique myectomy, was the most common surgery in both unilateral (n = 756, 77.1%) and bilateral (n = 35, 52.2%) patients. The second surgery was performed for 84 (8.6%) unilateral and 33 (49.3%) bilateral cases (P < 0.001). The prevalence of amblyopia and the mean angle of horizontal deviation were significantly higher in patients who needed more than one surgery (allP < 0.05).

Conclusion

Congenital SOP was more than twice as frequent as acquired SOP and about 90% of unilateral and 50% of bilateral cases were managed with one surgery. Amblyopia and significant horizontal deviation were the most important factors for reoperation.

Trial registration

The Institutional Review Board approval was obtained from the Tehran University of Medical Sciences (IR.TUMS.FNM.REC.1400.012) and this study adhered to the tenets of the Declaration of Helsinki and HIPAA.
Understanding the associations between information sources, sociodemographics, and views on public health measures: evidence from the COVID-19 pandemic in Austria
Authors: Gamillscheg Peter , Mayer Susanne , Pietrzak-Franger Monika , Hilmar Carina , Lange Alina , Simon Judit , Łaszewska Agata
Published: June 2024

Background

Throughout the COVID-19 pandemic, it was a key priority for governments globally to ensure agreement with, and subsequently adherence to, imposed public health measures, specifically non-pharmaceutical interventions (NPIs). Prior research in this regard highlighted the role of COVID-19 information sources as well as sociodemographic and other personal characteristics, however, there is only limited evidence including both. To bridge this gap, this study investigated the associations of COVID-19 information sources such as social media and participant characteristics with agreement with and adherence to NPIs during the first lockdown in Austria.

Methods

An online survey was conducted in May 2020 among adult Austrian residents asking about their experiences during the first lockdown. Collected data included sociodemographic characteristics, main COVID-19-related information sources, agreement with/adherence to three NPIs (no physical contact to family members not living in the same household, leisurely walks restricted to members of the same household, mandatory face masks) and information about perceived social support using the Multidimensional Scale of Perceived Social Support (MSPSS), anxiety/depression levels using the Hospital Anxiety and Depression Scale (HADS), whether participants felt well advised by the government, and whether participants perceived the pandemic to threaten their income. Ordered and multinomial logistic regression models were employed to achieve the research aims.

Results

The cross-sectional sample consisted of 559 Austrian residents. Using social media as main COVID-19 information source was consistently associated with lower agreement with NPIs. A positive association with agreement with measures was found for higher educational backgrounds and higher anxiety levels. By contrast, higher levels of depression, not feeling well advised by the government, and perceiving the pandemic as an economic threat were negatively associated with agreement with measures. Moreover, the use of social media as main COVID-19 information source and not feeling well advised by the government were associated with lower adherence to NPIs. By contrast, higher levels of education were associated with higher adherence.

Conclusions

This comprehensive analysis emphasizes the associations of COVID-19 information sources as well as sociodemographic and other participant characteristics with agreement with and adherence to NPIs, bearing important implications for future public health crisis communication strategies.
Exploring the microbiota difference of bronchoalveolar lavage fluid between community-acquired pneumonia with or without COPD based on metagenomic sequencing: a retrospective study
Authors: Wang Bingbing , Tan Min , Li Wei , Xu Qinghua , Jin Lianfeng , Xie Shuanshuan , Wang Changhui
Published: June 2024

Background

Community-acquired pneumonia (CAP) patients with chronic obstructive pulmonary disease (COPD) have higher disease severity and mortality compared to those without COPD. However, deep investigation into microbiome distribution of lower respiratory tract of CAP with or without COPD was unknown.

Methods

So we used metagenomic next generation sequencing (mNGS) to explore the microbiome differences between the two groups.

Results

Thirty-six CAP without COPD and 11 CAP with COPD cases were retrieved. Bronchoalveolar lavage fluid (BALF) was collected and analyzed using untargeted mNGS and bioinformatic analysis. mNGS revealed that CAP with COPD group was abundant with Streptococcus, Prevotella, Bordetella at genus level and Cutibacterium acnes, Rothia mucilaginosa, Bordetella genomosp. 6 at species level. While CAP without COPD group was abundant with Ralstonia, Prevotella, Streptococcus at genus level and Ralstonia pickettii, Rothia mucilaginosa, Prevotella melaninogenica at species level. Meanwhile, both alpha and beta microbiome diversity was similar between groups. Linear discriminant analysis found that pa-raburkholderia, corynebacterium tuberculostearicum and staphylococcus hominis were more enriched in CAP without COPD group while the abundance of streptococcus intermedius, streptococcus constellatus, streptococcus milleri, fusarium was higher in CAP with COPD group.

Conclusions

These findings revealed that concomitant COPD have an mild impact on lower airway microbiome of CAP patients.
Exploring heterogeneous expression of beta-actin (ACTB) in bladder cancer by producing a monoclonal antibody 6D6
Authors: Zareinejad Mohammadrasul , Faghih Zahra , Ramezani Amin , Safaei Akbar , Ghaderi Abbas
Published: June 2024

Background

To predict outcomes and identify potential therapeutic targets for cancers, it is critical to find novel specific biomarkers. The objective of this study was to search for and explore novel bladder cancer-associated protein biomarkers.

Methods

A library of monoclonal antibodies (mAbs) against the JAM-ICR cell line was first generated, and clones with high affinity were selected. Hybridomas were screened using bladder cancer (BLCA) cell lines and normal cells. The target of the selected mAb was then characterized through immunoaffinity purification, western blotting, and mass spectrometry analysis. Expression of the target antigen was assessed by flow cytometry and IHC methods. Several databases were also used to evaluate the target antigen in BLCA and other types of cancers.

Results

Based on screenings, a 6D6 clone was selected that recognized an isoform of beta-actin (ACTB). Our data showed that ACTB expression on different cell lines was heterogeneous and varied significantly from low to high intensity. 6D6 bound strongly to epithelial cells while showing weak to no reactivity to stromal, endothelial, and smooth muscle cells. There was no association between ACTB intensity and related prognostic factors in BLCA. In silico evaluations revealed a significant correlation between ACTB and overexpressed genes and biomarkers in BLCA. Additionally, the differential expression of ACTB in tumor and healthy tissue as well as its correlation with survival time in a number of cancers were shown.

Conclusions

The heterogeneous expression of ACTB may suggest the potential value of this marker in the diagnosis or prognosis of cancer.
Evaluation of surface tensions and root-dentin surface contact angles of different endodontic irrigation solutions
Authors: Buyukozer Ozkan Hatice , Terlemez Arslan , Batibay Ahmet Burcin , Erdogan Hilal , Kont Cobankara Funda
Published: June 2024

Background

Surface tension and contact angle properties, which play a crucial role in determining the effectiveness of irrigation solutions in penetrating dentin surfaces and dentin tubules, are highly important for the development of new irrigation solutions and their preferences. The aim of the current study was to compare the surface tension and contact angle properties of different irrigation solutions used in endodontics, both on the dentin surface and within dentin tubules.

Methods

In this study, the contact angles and surface tensions of 5.25% sodium hypochlorite (NaOCl), 17% ethylenediaminetetraacetic acid (EDTA), 2% chlorhexidine (CHX), 5% boric acid (BA), 0.02% hypochlorous acid (HOCl), 0.2% chlorine dioxide (ClO2), Biopure MTAD, QMix solutions, and distilled water (control group) were measured. Measurements were conducted using a goniometer device (Attension Theta Lite Tensiometer, Biolin Scientific, USA), employing the sessile drop method for contact angle measurements on pre-prepared dentin surfaces, and the pendant drop method for surface tension.

Results

Contact angle measurements revealed no statistically significant differences between the contact angle values of MTAD, ClO2, and CHX or between NaOCl, QMix, BA, and HOCl (p > 0.05). However, EDTA exhibited a significantly greater contact angle than did MTAD, ClO2, CHX, NaOCl, QMix, BA, and HOCl (p < 0.05). Furthermore, the contact angle of dentin with distilled water was greater than that with all other solutions tested (p < 0.05). Surface tension measurements revealed that the surface tension values of QMix and MTAD were statistically similar (p > 0.05). CHX exhibited lower surface tension than distilled water and HOCl (p < 0.05), and it also had lower surface tension than ClO2, NaOCl, and BA (p < 0.05). Additionally, the surface tension of the samples treated with EDTA was greater than that of all other solutions tested (p < 0.05).

Conclusion

The direct linear relationship between the surface tension of liquids and contact angles on different surfaces may not always hold true, and these values should be considered independently for each solution on various surfaces. Considering the contact angles and surface tension properties of irrigation solutions with root canal dentin, it can be suggested for clinical use that ClO2 could be recommended over NaOCl, and similarly, BA could be recommended over EDTA.
An integrative review of the impact of allied health student placements on current staff’s knowledge and procedural skills in acute and primary care settings
Authors: Hamiduzzaman Mohammad , Miles Sarah , Crook Sarah , Grove Lewis , Hewitt Jennie , Barraclough Frances , Hawkins Peter , Campbell Erika , Buster Nicola , Thomson Kate , Williams Christopher , Flood Vicki
Published: June 2024

Background

Staff shortages limit access to health services. The bidirectional benefits of allied health clinical placements are understood in the domains of student learning, health service delivery, and future workforce development. Still, the benefits to current workforce outcomes remain unknown. This review provides insights into the effects of allied health student placements in acute and primary care settings, particularly on healthcare staff's knowledge and procedural skills.

Methods

This search was based on the integrative review process established by Whittemore and Knafl in 2005. In October 2023, the first author (MH) searched five major electronic databases: Medline-EBSCO, PubMed, CINAHL, Embase, and Scopus. The CLUSTER model was used to track additional references. The first three authors (MH, SM, and SC) were involved in screening, quality appraisal, and synthesis of the studies. Data were thematically synthesised and analysed.

Results

MeSH headings and keywords were used in key search areas: health education, health professional training, clinical placements, and allied health professions. The systematic search yielded 12 papers on allied health student placements across various healthcare settings in rural and metropolitan areas, with no high-quality methodologies measuring student placements' impact on staff knowledge and skills. Four main themes were identified from the analysis: meaningful student integration in service delivery, targeted educational support to healthcare staff, development of staff procedural skills and confidence, and the mechanisms of why student placements work in this aspect.

Conclusions

This review suggests that offering allied health student placement could be a promising approach to supporting rural healthcare staff in performing patient assessments and treatments proficiently and collaboratively. However, this requires further investigation to confirm.
Impact of mobile application and outpatient follow-up on renal endpoints and physiological indices in patients with chronic kidney disease: a retrospective cohort study in Southwest China
Authors: Shi Yu , Pu Shi , Peng Hongmei , Zhang Jing , Li Yang , Huang Xia , Song Caiping , Luo Yu
Published: June 2024

Background

Chronic kidney disease (CKD) is a significant public health concern, and patient self-management is an effective approach to manage the condition. Mobile applications have been used as tools to assist in improving patient self-management, but their effectiveness in long-term outpatient follow-up management of patients with CKD remains to be validated. This study aimed to investigate whether using a mobile application combined with traditional outpatient follow-up can improve health outcomes of patients with CKD .

Methods

This retrospective cohort study recruited CKD patients with stage 1–5 who were not receiving renal replacement therapy from a CKD management center. Two groups were established: the APP + outpatient follow-up group and the traditional outpatient follow-up group. Baseline data was collected from January 2015 to December 2019, followed by a three-year long-term follow-up until December 2022. Laboratory data, all-cause mortality, and renal replacement treatment were then collected and compared between the two groups.

Results

5326 patients were included in the study, including 2492 in the APP + outpatient group and 2834 in the traditional outpatient group. After IPTW virtualization matching, the final matched the APP + outpatient group consisted of 2489 cases (IQR, 33–55) and 2850 (IQR, 33–55) in the traditional outpatient group. By the end of the study, it was observed that the laboratory data of Phosphorus, Sodium, Triglyceride, Hemoglobin showed significant improvements, Furthermore the APP + outpatient group demonstrated superior results compared to the traditional outpatient group (P < .05). And it was observed that there were 34 deaths (1.4%) in the APP + outpatient group and 46 deaths (1.6%) in the traditional outpatient group(P = .49). After matching for renal replacement therapy outcomes, the two groups were found to be comparable (95% CI [0.72–1.08], P = .23), with no significant difference. However, it was noted that the traditional outpatient group had a lower incidence of using temporary catheters during initial hemodialysis (95% CI [8.4-29.8%], P < .001).

Conclusion

The development and application of an app combined with outpatient follow-up management can improve patient health outcomes. However, to ensure optimal preparation for kidney replacement therapy, patients in CKD stages 4–5 may require more frequent traditional outpatient follow-ups, and further develop an information-based decision-making support tool for renal replacement therapy.
Factors influencing senior care and living preferences among older adults in Jiangsu, China: a cross-sectional survey study
Authors: Wang Yanan , Wang Yaning , Liu Yitong , Xu Wenkun , Yang Zhuoya , Xu Zhongying , Zhong Yaqin
Published: June 2024

Background

As the population ages, senior care for older adults in China has become increasingly important and has attracted the attention of both government and society. This study aimed to explore preferences and influencing factors related to senior care among older Chinese adults and thus propose effective and targeted strategies for the development of a comprehensive care system for older adults in the aging Chinese population.

Methods

Data were obtained from a cross-sectional survey conducted in sixteen communities or villages in Jiangsu Province, China, from July to September 2021. Guided by the Andersen Behavioral Model, multivariate logistic regression was conducted to identify factors associated with preferences for senior care arrangements.

Results

A total of 870 respondents were included in the study, 60.11% of whom preferred receiving care in their own homes, while only 13.68% chose residential care facilities (RCFs). For predisposing factors, rural respondents preferred receiving care in their own homes compared to urban respondents (children’s home: OR = 0.55, P < 0.01; RCF: OR = 0.58, P < 0.01). Concerning enabling factors, respondents who were not employed (OR = 2.30, P < 0.01) and those without financial support (OR = 2.73, P < 0.05) preferred RCFs to their own homes. Respondents receiving life assistance (sometimes: OR = 2.76, P < 0.001; regularly: OR = 2.57, P < 0.01; every day: OR = 3.57, P < 0.001) preferred their children’s homes to their own homes. In terms of need factors, respondents with noncommunicable diseases (NCDs, OR > 1, P < 0.05), those who knew about RCFs (some: OR = 0.53, P < 0.005; no: OR = 0.10, P < 0.001) and those with a good impression of RCFs (fair: OR = 3.72, P < 0.05; good: OR = 11.91, P < 0.001) preferred receiving care in RCFs compared to their counterparts.

Conclusions

Older Chinese adults’ senior care preferences were affected by predisposing factors, enabling factors, and need factors. Policy-makers should consider targeted measures to identify more precise senior care services and thus address aging challenges in China.
Combined associations of visceral adipose tissue and adherence to a Mediterranean lifestyle with T2D and diabetic microvascular complications among individuals with prediabetes
Authors: Chen Hao-Wen , Liu Kuan , Cao Bi-Fei , Zhong Qi , Zhou Rui , Li Liang-Hua , Wang Shi-Ao , Wei Yan-Fei , Liu Hua-Min , Wu Xian-Bo
Published: June 2024

Background

It’s unclear if excess visceral adipose tissue (VAT) mass in individuals with prediabetes can be countered by adherence to a Mediterranean lifestyle (MEDLIFE). We aimed to examine VAT mass, MEDLIFE adherence, and their impact on type 2 diabetes (T2D) and diabetic microvascular complications (DMC) in individuals with prediabetes.

Methods

11,267 individuals with prediabetes from the UK Biobank cohort were included. VAT mass was predicted using a non-linear model, and adherence to the MEDLIFE was evaluated using the 25-item MEDLIFE index, encompassing categories such as “Mediterranean food consumption,” “Mediterranean dietary habits,” and “Physical activity, rest, social habits, and conviviality.” Both VAT and MEDLIFE were categorized into quartiles, resulting in 16 combinations. Incident cases of T2D and related DMC were identified through clinical records. Cox proportional-hazards regression models were employed to examine associations, adjusting for potential confounding factors.

Results

Over a median follow-up of 13.77 years, we observed 1408 incident cases of T2D and 714 cases of any DMC. High adherence to the MEDLIFE, compared to the lowest quartile, reduced a 16% risk of incident T2D (HR: 0.84, 95% CI: 0.71–0.98) and 31% for incident DMC (0.69, 0.56–0.86). Conversely, compared to the lowest quartile of VAT, the highest quartile increased the risk of T2D (5.95, 4.72–7.49) and incident any DMC (1.79, 1.36–2.35). We observed an inverse dose-response relationship between MEDLIFE and T2D/DMC, and a dose-response relationship between VAT and all outcomes (P for trend < 0.05). Restricted cubic spline analysis confirmed a nearly linear dose-response pattern across all associations. Compared to individuals with the lowest MEDLIFE quartile and highest VAT quartile, those with the lowest T2D risk had the lowest VAT and highest MEDLIFE (0.12, 0.08–0.19). High MEDLIFE was linked to reduced T2D risk across all VAT categories, except in those with the highest VAT quartile. Similar trends were seen for DMC.

Conclusion

High adherence to MEDLIFE reduced T2D and MDC risk in individuals with prediabetes, while high VAT mass increases it, but MEDLIFE adherence may offset VAT’s risk partly. The Mediterranean lifestyle’s adaptability to diverse populations suggests promise for preventing T2D.
Bidirectional modulation of TCA cycle metabolites and anaplerosis by metformin and its combination with SGLT2i
Authors: Harada Makoto , Adam Jonathan , Covic Marcela , Ge Jianhong , Brandmaier Stefan , Muschet Caroline , Huang Jialing , Han Siyu , Rommel Martina , Rotter Markus , Heier Margit , Mohney Robert P. , Krumsiek Jan , Kastenmüller Gabi , Rathmann Wolfgang , Zou Zhongmei , Zukunft Sven , Scheerer Markus F. , Neschen Susanne , Adamski Jerzy , Gieger Christian , Peters Annette , Ankerst Donna P. , Meitinger Thomas , Alderete Tanya L. , de Angelis Martin Hrabe , Suhre Karsten , Wang-Sattler Rui
Published: June 2024

Background

Metformin and sodium-glucose-cotransporter-2 inhibitors (SGLT2i) are cornerstone therapies for managing hyperglycemia in diabetes. However, their detailed impacts on metabolic processes, particularly within the citric acid (TCA) cycle and its anaplerotic pathways, remain unclear. This study investigates the tissue-specific metabolic effects of metformin, both as a monotherapy and in combination with SGLT2i, on the TCA cycle and associated anaplerotic reactions in both mice and humans.

Methods

Metformin-specific metabolic changes were initially identified by comparing metformin-treated diabetic mice (MET) with vehicle-treated db/db mice (VG). These findings were then assessed in two human cohorts (KORA and QBB) and a longitudinal KORA study of metformin-naïve patients with Type 2 Diabetes (T2D). We also compared MET with db/db mice on combination therapy (SGLT2i + MET). Metabolic profiling analyzed 716 metabolites from plasma, liver, and kidney tissues post-treatment, using linear regression and Bonferroni correction for statistical analysis, complemented by pathway analyses to explore the pathophysiological implications.

Results

Metformin monotherapy significantly upregulated TCA cycle intermediates such as malate, fumarate, and α-ketoglutarate (α-KG) in plasma, and anaplerotic substrates including hepatic glutamate and renal 2-hydroxyglutarate (2-HG) in diabetic mice. Downregulated hepatic taurine was also observed. The addition of SGLT2i, however, reversed these effects, such as downregulating circulating malate and α-KG, and hepatic glutamate and renal 2-HG, but upregulated hepatic taurine. In human T2D patients on metformin therapy, significant systemic alterations in metabolites were observed, including increased malate but decreased citrulline. The bidirectional modulation of TCA cycle intermediates in mice influenced key anaplerotic pathways linked to glutaminolysis, tumorigenesis, immune regulation, and antioxidative responses.

Conclusion

This study elucidates the specific metabolic consequences of metformin and SGLT2i on the TCA cycle, reflecting potential impacts on the immune system. Metformin shows promise for its anti-inflammatory properties, while the addition of SGLT2i may provide liver protection in conditions like metabolic dysfunction-associated steatotic liver disease (MASLD). These observations underscore the importance of personalized treatment strategies.
Citrate synthase variants improve yield of acetyl-CoA derived 3-hydroxybutyrate in Escherichia coli
Authors: Rajpurohit Hemshikha , Eiteman Mark A.
Published: June 2024

Background

The microbial chiral product (R)-3-hydroxybutyrate (3-HB) is a gateway to several industrial and medical compounds. Acetyl-CoA is the key precursor for 3-HB, and several native pathways compete with 3-HB production. The principal competing pathway in wild-type Escherichia coli for acetyl-CoA is mediated by citrate synthase (coded by gltA), which directs over 60% of the acetyl-CoA into the tricarboxylic acid cycle. Eliminating citrate synthase activity (deletion of gltA) prevents growth on glucose as the sole carbon source. In this study, an alternative approach is used to generate an increased yield of 3-HB: citrate synthase activity is reduced but not eliminated by targeted substitutions in the chromosomally expressed enzyme.

Results

Five E. coli GltA variants were examined for 3-HB production via heterologous overexpression of a thiolase (phaA) and NADPH-dependent acetoacetyl-CoA reductase (phaB) from Cupriavidus necator. In shake flask studies, four variants showed nearly 5-fold greater 3-HB yield compared to the wild-type, although pyruvate accumulated. Overexpression of either native thioesterases TesB or YciA eliminated pyruvate formation, but diverted acetyl-CoA towards acetate formation. Overexpression of pantothenate kinase similarly decreased pyruvate formation but did not improve 3-HB yield. Controlled batch studies at the 1.25 L scale demonstrated that the GltA[A267T] variant produced the greatest 3-HB titer of 4.9 g/L with a yield of 0.17 g/g. In a phosphate-starved repeated batch process, E. coli ldhA poxB pta-ackA gltA::gltA[A267T] generated 15.9 g/L 3-HB (effective concentration of 21.3 g/L with dilution) with yield of 0.16 g/g from glucose as the sole carbon source.

Conclusions

This study demonstrates that GltA variants offer a means to affect the generation of acetyl-CoA derived products. This approach should benefit a wide range of acetyl-CoA derived biochemical products in E. coli and other microbes. Enhancing substrate affinity of the introduced pathway genes like thiolase towards acetyl-CoA will likely further increase the flux towards 3-HB while reducing pyruvate and acetate accumulation.
Racial inequalities in the development of multimorbidity of chronic conditions: results from a Brazilian prospective cohort
Authors: Oliveira Fernanda Esthefane Garrides , Griep Rosane Härter , Chor Dora , Barreto Sandhi Maria , Molina Maria del Carmen Bisi , Machado Luciana A. C. , Fonseca Maria de Jesus Mendes da , Bastos Leonardo Soares
Published: June 2024

Background

The occurrence of multimorbidity and its impacts have differentially affected population subgroups. Evidence on its incidence has mainly come from high-income regions, with limited exploration of racial disparities. This study investigated the association between racial groups and the development of multimorbidity and chronic conditions in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Methods

Data from self-reported white, brown (pardos or mixed-race), and black participants at baseline of ELSA-Brasil (2008–2010) who were at risk for multimorbidity were analysed. The development of chronic conditions was assessed through in-person visits and self-reported diagnosis via telephone until the third follow-up visit (2017–2019). Multimorbidity was defined when, at the follow-up visit, the participant had two or more morbidities. Cumulative incidences, incidence rates, and adjusted incidence rate ratios (IRRs) were estimated using Poisson models.

Results

Over an 8.3-year follow-up, compared to white participants: browns had a 27% greater incidence of hypertension and obesity; and blacks had a 62% and 45% greater incidence, respectively. Blacks also had 58% more diabetes. The cancer incidence was greater among whites. Multimorbidity affected 41% of the participants, with a crude incidence rate of 57.5 cases per 1000 person-years (ranging from 56.3 for whites to 63.9 for blacks). Adjusted estimates showed a 20% higher incidence of multimorbidity in black participants compared to white participants (IRR: 1.20; 95% CI: 1.05–1.38).

Conclusions

Significant racial disparities in the risk of chronic conditions and multimorbidity were observed. Many associations revealed a gradient increase in illness risk according to darker skin tones. Addressing fundamental causes such as racism and racial discrimination, alongside considering social determinants of health, is vital for comprehensive multimorbidity care. Intersectoral, equitable policies are essential for ensuring health rights for historically marginalized groups.
LDLR c.89_92dup: a novel frameshift variation in familial hypercholesterolemia
Authors: Deng Jialing , Zhang Ju , Meng Shirui , Ding Nan , Hao Yu , Zeng Hui , Lin Jie
Published: June 2024

Background

Familial hypercholesterolemia (FH) is a common inherited metabolic disease that causes premature atherosclerosis, cardiovascular disease, and even death at a young age. Approximately 95% of FH-causing genetic variants that have been identified are in the LDLR gene. However, only 10% of the FH population worldwide has been diagnosed and adequately treated, due to the existence of numerous unidentified variants, uncertainties in the pathogenicity scoring of many variants, and a substantial number of individuals lacking access to genetic testing.

Objective

The aim of this study was to identify a novel variant in the LDLR gene that causes FH in a Chinese family, thereby expanding the spectrum of FH-causing variants.

Methods

Patients were recruited from Beijing Anzhen Hospital, Capital Medical University. FH diagnosis was made according to the Dutch Lipid Clinical Network (DLCN) criteria. Whole-exome sequencing (WES) was conducted to identify the FH-causing variant in the proband, and amplicon sequencing was used to verify the variant in his family members.

Results

A three-generation Chinese family was recruited, and two FH patients were clinically diagnosed, both without known FH-causing variants. These two FH patients and another possible patient carried a novel variant, NC_000019.9(NM_000527.5):c.89_92dup (NP_000518.1:p.Phe32Argfs*21), in the ligand-binding domain of the low-density lipoprotein (LDL) receptor that led to a frameshift. The FH adults in the family showed severe clinical symptoms and statin therapy resistance.

Conclusion

This study identified a novel pathogenic LDLR variant, c.89_92dup, associated with severe FH clinical manifestations and statin therapy resistance.
Podoplanin depletion in tonsil-derived mesenchymal stem cells induces cellular senescence via regulation of the p16Ink4a/Rb pathway
Authors: Kim Ha Yeong , Kim Han Su
Published: June 2024

Background

Mesenchymal stem cells (MSCs) are widely used in the development of therapeutic tools in regenerative medicine. However, their quality decreases during in vitro expansion because of heterogeneity and acquired cellular senescence. We investigated the potential role of podoplanin (PDPN) in minimizing cellular senescence and maintaining the stemness of tonsil-derived MSCs (TMSCs).

Methods

TMSCs were isolated from human tonsil tissues using an enzymatic method, expanded, and divided into two groups: early-passaged TMSCs, which were cultured for 3–7 passages, and late-passaged TMSCs, which were passaged more than 15 times. The TMSCs were evaluated for cellular senescence and MSC characteristics, and PDPN-positive and -negative cells were identified by fluorescence-activated cell sorting. In addition, MSC features were assessed in siRNA-mediated PDPN-depleted TMSCs.

Results

TMSCs, when passaged more than 15 times and becoming senescent, exhibited reduced proliferative rates, telomere length, pluripotency marker (NANOG, OCT4, and SOX2) expression, and tri-lineage differentiation potential (adipogenesis, chondrogenesis, or osteogenesis) compared to cells passaged less than five times. Furthermore, PDPN protein levels significantly decreased in a passage-dependent manner. PDPN-positive cells maintained their stemness characteristics, such as MSC-specific surface antigen (CD14, CD34, CD45, CD73, CD90, and CD105) and pluripotency marker expression, and exhibited higher tri-lineage differentiation potential than PDPN-negative cells. SiRNA-mediated silencing of PDPN led to decreased cell-cycle progression, proliferation, and migration, indicating the significance of PDPN as a preliminary senescence-related factor. These reductions directly contributed to the induction of cellular senescence via p16Ink4a/Rb pathway activation.

Conclusion

PDPN may serve as a novel biomarker to mitigate cellular senescence in the clinical application of MSCs.

Graphical Abstract
Scaling up a brief alcohol intervention to prevent HIV infection in Vietnam: a cluster randomized, implementation trial
Authors: Bartels Sophia M. , Phan Huong T. T. , Hutton Heidi E. , Nhan Do T. , Sripaipan Teerada , Chen Jane S. , Rossi Sarah L. , Ferguson Olivia , Nong Ha T. T. , Nguyen Ngan T. K. , Giang Le Minh , Bui Hao T. M. , Chander Geetanjali , Sohn Hojoon , Kim Sol , Tran Ha V. , Nguyen Minh X. , Powell Byron J. , Pence Brian W. , Miller William C. , Go Vivian F.
Published: June 2024

Background

Evidence-based interventions (EBIs) often address normative behaviors. If a behavior is also common among clinicians, they may be skeptical about the necessity or effectiveness of an EBI. Alternatively, clinicians’ attitudes and behaviors may be misaligned, or they may lack the knowledge and self-efficacy to deliver the EBI. Several EBIs address unhealthy alcohol use, a common and often culturally acceptable behavior. But unhealthy alcohol use may be particularly harmful to people with HIV (PWH). Here, we present an implementation trial using an experiential implementation strategy to address clinicians’ knowledge, attitudes, and behaviors. Clinicians receive the experiential intervention before they begin delivering an evidence-based brief alcohol intervention (BAI) to PWH with unhealthy alcohol use.

Methods

Design: In this hybrid type 3 implementation-effectiveness cluster randomized controlled trial, ART clinics (n = 30) will be randomized 1:1 to facilitation, a flexible strategy to address implementation barriers, or facilitation plus the experiential brief alcohol intervention (EBAI). In the EBAI arm, clinicians, irrespective of their alcohol use, will be offered the BAI as experiential learning. EBAI will address clinicians’ alcohol-related attitudes and behaviors and increase their knowledge and confidence to deliver the BAI.

Participants: ART clinic staff will be enrolled and assessed at pre-BAI training, post-BAI training, 3, 12, and 24 months. All PWH at the ART clinics who screen positive for unhealthy alcohol use will be offered the BAI. A subset of PWH (n = 810) will be enrolled and assessed at baseline, 3, and 12 months.

Outcomes: We will compare implementation outcomes (acceptability, fidelity, penetration, costs, and sustainability) and effectiveness outcomes (viral suppression and alcohol use) between the two arms. We will assess the impact of site-level characteristics on scaling-up the BAI. We will also evaluate how experiencing the BAI affected clinical staff’s alcohol use and clinic-level alcohol expectations in the EBAI arm.

Discussion

This trial contributes to implementation science by testing a novel strategy to implement a behavior change intervention in a setting in which clinicians themselves may engage in the behavior. Experiential learning may be useful to address normative and difficult to change lifestyle behaviors that contribute to chronic diseases.

Trial Registration

NCT06358885 (04/10/2024), https://clinicaltrials.gov/study/NCT06358885.
Gene count normalization in single-cell imaging-based spatially resolved transcriptomics
Authors: Atta Lyla , Clifton Kalen , Anant Manjari , Aihara Gohta , Fan Jean
Published: June 2024

Background

Recent advances in imaging-based spatially resolved transcriptomics (im-SRT) technologies now enable high-throughput profiling of targeted genes and their locations in fixed tissues. Normalization of gene expression data is often needed to account for technical factors that may confound underlying biological signals.

Results

Here, we investigate the potential impact of different gene count normalization methods with different targeted gene panels in the analysis and interpretation of im-SRT data. Using different simulated gene panels that overrepresent genes expressed in specific tissue regions or cell types, we demonstrate how normalization methods based on detected gene counts per cell differentially impact normalized gene expression magnitudes in a region- or cell type-specific manner. We show that these normalization-induced effects may reduce the reliability of downstream analyses including differential gene expression, gene fold change, and spatially variable gene analysis, introducing false positive and false negative results when compared to results obtained from gene panels that are more representative of the gene expression of the tissue’s component cell types. These effects are not observed with normalization approaches that do not use detected gene counts for gene expression magnitude adjustment, such as with cell volume or cell area normalization.

Conclusions

We recommend using non-gene count-based normalization approaches when feasible and evaluating gene panel representativeness before using gene count-based normalization methods if necessary. Overall, we caution that the choice of normalization method and gene panel may impact the biological interpretation of the im-SRT data.
The effect of different flushing and locking techniques on catheter occlusion rates in central venous catheters: protocol for a multicentre, randomized controlled, parallel-group, open-label, superiority clinical trial
Authors: Li Rongmei , Zhou Mian , Sun Lulu , Sha Lili , Xu Biyun , Li Taishun , Tao Tingting , Yuan Ling
Published: June 2024

Background

Maintaining venous access is of great clinical importance. Running a slow continuous infusion to keep the vein open (KVO) is often used in peripheral intravenous catheters (PIVCs). Previous studies have compared the effects of intermittent flushing and continuous infusion via peripherally inserted central catheters (PICCs). In this study, we applied KVO to central venous catheters (CVCs) and compared the occlusion rate of this technique with that of the intermittent flushing technique.

Method

This is a randomized controlled trial of 14 hospitals in China. A total of 250 patients will be recruited in this study, and they will be randomized at a 1:1 ratio. After study inclusion, patients who will undergo CVC insertion will receive intermittent flushing with prefilled saline syringes (control group) or KVO infusion with elastic pumps (test group). All the catheters will be checked for patency by scoping Catheter Injection and Aspiration (CINAS) Classification on Days 3 and 7. The primary outcome is the rate of catheter occlusion in 7 days. Patients will be followed up until 9 days after CVC insertion, catheter occlusion, or catheter removal. The secondary outcomes are the rate of catheter occlusion in 3 days, nurse satisfaction, cost-effectiveness, adverse event rate, catheter-related bloodstream infection rate, catheter-related thrombosis rate, extravasation rate, phlebitis rate, and catheter migration.

Discussion

We expect that the trial will generate findings that can provide an evidence-based basis for the improvement and optimization of clinical catheter flushing techniques.

Trial registration

Chinese Clinical Trial Registry, ChiCTR2200064007. Registered on 23 September 2022. https://www.chictr.org.cn/showproj.html?proj=177311.
Recommendations on the use of the flash continuous glucose monitoring system in hospitalized patients with diabetes in Latin America
Authors: Gómez Ana María , Henao Carrillo Diana Cristina , Ré Matías Alberto , Faradji Raquel N. , Flores Caloca Oscar , de la Garza Hernández Natalia Eloísa , Antillón Ferreira Carlos , Garnica-Cuéllar Juan C. , Krakauer Marcio , Galindo Rodolfo J.
Published: June 2024

Background

Continuous glucose monitoring can improve glycemic control for hospitalized patients with diabetes, according to current evidence. However, there is a lack of consensus-established recommendations for the management of hospitalized patients with diabetes using flash continuous glucose monitoring system (fCGM) in Latin America. Therefore, this expert consensus exercise aimed to establish guidelines on the implementation of fCGM in the management of hospitalized patients with diabetes in Latin America.

Methods

The modified Delphi method was applied on a panel of nine specialists, establishing consensus at 80%. A twenty-two-question instrument was developed to establish recommendations on the use of fCGM in hospitalized patients living with diabetes.

Results

Based on consensus, experts recommend the use of fCGM in hospitalized patients with diabetes starting at admission or whenever hyperglycemia (> 180 mg/dl) is confirmed and continue monitoring throughout the entire hospital stay. The recommended frequency of fCGM scans varies depending on the patient's age and diabetes type: ten scans per day for pediatric patients with type 1 and 2 diabetes, adult patients with type 1 diabetes and pregnant patients, and seven scans for adult patients with type 2 diabetes. Different hospital services can benefit from fCGM, including the emergency room, internal medicine departments, intensive care units, surgery rooms, and surgery wards.

Conclusions

The use of fCGM is recommended for patients with diabetes starting at the time of admission in hospitals in Latin America, whenever the necessary resources (devices, education, personnel) are available.
Temperature effect on coagulation function in mild hypothermic patients undergoing thoracic surgeries: thromboelastography (TEG) versus standard tests
Authors: Hui Shangyi , Zhang Qian , Lang Jiaxin , Yi Jie
Published: June 2024

Purpose

Our previous research has revealed that mild hypothermia leads to excessive bleeding in thoracic surgeries, while the underlying mechanism stayed unrevealed by the standard coagulation tests. The research question in this study was as follows: “How does mild hypothermia impair the hemostatic function in patients receiving thoracic surgeries?”. The purpose was to detect the disturbed coagulation processes by comparing the TEG parameters in patients receiving active vs. passive warming during thoracic surgeries.

Methods

Standard coagulation tests and thromboelastography (TEG) were adopted to compare the hemostatic functions in patients receiving active vs. passive warming during thoracic surgeries. Furthermore, blood samples from passive warming group were retested for TEG at actual core body temperatures.

Results

Sixty-four eligible patients were included in this study. TEG revealed that mild hypothermia significantly disturbed coagulation by decreasing MA (59.4 ± 4.5 mm vs. 64.2 ± 5.7 mm, p = 0.04) and α angle (70.4 ± 5.2° vs. 74.9 ± 4.4°, p = 0.05) and prolonging ACT (122.2 ± 19.3 s vs. 117.3 ± 15.2 s, p = 0.01) and K time (1.9 ± 1.0 s vs. 1.3 ± 0.4 min, p = 0.02). TEGs conducted under core body temperatures revealed more impaired coagulation than those incubated at 37 °C. Furthermore, postoperative shivering and waking time were significantly increased in mild hypothermic patients.

Conclusion

Mild hypothermia significantly impaired coagulation function in patients receiving thoracic surgeries, which could be detected by TEGs other than the standard coagulation tests. Temperature-adjusted TEGs may provide a preferable method of hemostatic monitoring and transfusion guidance in thoracic surgeries, which warrants further clinical investigations.
Impact of annual trend volume of low-dose computed tomography for lung cancer screening on overdiagnosis, overmanagement, and gender disparities
Authors: Hsin-Hung Chen , En-Kuei Tang , Yun-Ju Wu , Fu-Zong Wu
Published: June 2024

Background

With the increasing prevalence of nonsmoking-related lung cancer in Asia, Asian countries have increasingly adopted low-dose computed tomography (LDCT) for lung cancer screening, particularly in private screening programs. This study examined how annual LDCT volume affects lung cancer stage distribution, overdiagnosis, and gender disparities using a hospital-based lung cancer database.

Methods

This study analyzed the annual utilized LDCT volume, clinical characteristics of lung cancer, stage shift distribution, and potential overdiagnosis. At the individual level, this study also investigated the relationship between stage 0 lung cancer (potential strict definition regarding overdiagnosis) and the clinical characteristics of lung cancer.

Results

This study reviewed the annual trend of 4971 confirmed lung cancer cases from 2008 to 2021 and conducted a link analysis with an LDCT imaging examination database over these years. As the volume of lung cancer screenings has increased over the years, the number and proportion of stage 0 lung cancers have increased proportionally.

Our study revealed that the incidence of stage 0 lung cancer increased with increasing LDCT scan volume, particularly during the peak growth period from 2017 to 2020. Conversely, stage 4 lung cancer cases remained consistent across different time intervals. Furthermore, the increase in the lung cancer screening volume had a more pronounced effect on the increase in stage 0 lung cancer cases among females than it had among males. The estimated potential for overdiagnosis brought about by the screening process, compared to non-participating individuals, ranged from an odds ratio of 7.617 to one of 17.114. Both strict and lenient definitions of overdiagnosis (evaluating cases of stage 0 lung cancer and stages 0 to 1 lung cancer) were employed.

Conclusions

These results provide population-level evidence of potential lung cancer overdiagnosis in the Taiwanese population due to the growing use of LDCT screening, particularly concerning the strict definition of stage 0 lung cancer. The impact was greater in the female population than in the male population, especially among females younger than 40 years.

To improve lung cancer screening in Asian populations, creating risk-based prediction models for smokers and nonsmokers, along with gender-specific strategies, is vital for ensuring survival benefits and minimizing overdiagnosis.