bluuebunny/crossref_metadata_2025 huggingface dataset:
Neighborhood Gentrification and Food Insecurity Among Urban Older Adults: Evidence From New York City
Authors: Cheung Ethan Siu Leung
Published: May 2024

Background and Objectives

Gentrification is a prevalent neighborhood development process in urban areas across the United States. Prior studies have identified the influence of gentrification on late-life health and quality of life, yet little is known about its relationship with food insecurity, an important public health issue for older adult populations. Using New York City as a case study, this study investigated associations between living in a gentrifying neighborhood and food insecurity, as well as the mediating roles of neighborhood environment factors—social cohesion, public transportation, and food environment.

Research Design and Methods

This study adopted 2 waves of annual data from the Poverty Tracker Study (2015–2016; N = 703) merged with American Community Survey and spatial data sets to measure gentrification and neighborhood factors. Adjusted logistic regressions were used to examine the associations between gentrification and food insecurity. Further mediation analyses were conducted to test the mechanisms of such associations.

Results

Older adults in gentrifying neighborhoods were more likely to have food insecurity than those in moderate- to high-income neighborhoods. Compared to low-income neighborhoods, older adults in gentrifying neighborhoods had a lower likelihood of reporting food insecurity. Two significant mediators were found when comparing gentrification with moderate- to high-income neighborhoods: social cohesion and healthy food outlets.

Discussion and Implications

This study highlights the importance of gentrification in determining late-life food insecurity and identifies possible mechanisms with policy and social service implications to reduce the risk of food insecurity in urban areas.
The role of regulatory T-cells in the development of endometriosis
Authors: Knez Jure , Kovačič Borut , Goropevšek Aleš
Published: May 2024

Endometriosis is a benign disease of the female reproductive tract, characterized by the process of chronic inflammation and alterations in immune response. It is estimated to affect 2–19% of women in the general population and is commonly associated with symptoms of chronic pelvic pain and infertility. Regulatory T cells (Treg) are a subpopulation of T lymphocytes that are potent suppressors of inflammatory immune response, essential in preventing destructive immunity in all tissues. In endometriosis, several studies have investigated the possible role of Treg cells in the development of the disease. Most studies to date are heterogeneous in methodology and are based on a small number of cases, which means that it is impossible to define their exact role at present. Based on current knowledge, it seems that disturbed Treg homeostasis, leading to increased systemic and local inflammation within ectopic and eutopic endometrium, is present in women who eventually develop endometriosis. It is also evident that different subsets of human Treg cells have different roles in suppressing the immune response. Recent studies in patients with endometriosis have investigated naive/resting FOXP3lowCD45RA+ Treg cells, which upon T cell receptor stimulation, differentiate into activated/effector FOXP3highCD45RA− Treg cells, characterized by a strong immunosuppressive activity. In addition, critical factors controlling expression of Treg/effector genes, including reactive oxygen species and heme-responsive master transcription factor BACH2, were found to be upregulated in endometriotic lesions. As shown recently for cancer microenvironments, microbial inflammation may also contribute to the local composition of FOXP3+ subpopulations in endometriotic lesions. Furthermore, cytokines, such as IL-7, which control the homeostasis of Treg subsets through the tyrosine phosphorylation STAT5 signalling pathway, have also been shown to be dysregulated. To better understand the role of Treg in the development of endometriosis, future studies should use clear definitions of Tregs along with specific characterization of the non-Treg (FOXP3lowCD45RA−) fraction, which itself is a mixture of follicular Tregs and cells producing inflammatory cytokines.
Too busy to balance? A longitudinal analysis of board of director busyness and firms’ ambidextrous orientation
Authors: Heyden Mariano L. M , Fourné Sebastian P. L , Matthews Lane , Wilden Ralf , Tarkovska Valentina
Published: May 2024

Studies commonly highlight the informational upside of a board of directors’ connections to its external environment. Through their seats on multiple outside boards, directors are positioned to bring valuable informational resources to complex internal tasks on a focal firm. Crafting an ambidextrous strategic orientation is such a task, requiring great informational resourcing from a board to reconcile contradictions of exploration and exploitation. Yet, we assign an important boundary condition to this expectation by unpacking the idea of “busyness” as an important consideration in a board’s (in)ability to apply their informational resources. We complement Resource Dependence Theory with insights from bounded rationality and bounded reliability, to challenge the “more is better” assumption of the benefits of outside board seats. We develop corresponding hypotheses on the extent to which busyness of different director types (exemplified here via the busyness of non-executives, executives, and women directors) is related to the ambidextrous strategic orientation of a firm. Our results from a robust longitudinal panel analysis of publicly listed UK firms uncover complex patterns and provide evidence that boards with busy non-executives have a negative influence on the ambidextrous strategic orientation of firms, whereas boards with busy executive directors do not seem to exert an influence. We further find that boards with busy women directors show an inverted U-shaped relation with ambidextrous strategic orientation. We discuss implications for theory and practice.
Reactivation of a Transplant Recipient's Inherited Human Herpesvirus 6 and Implications to the Graft
Authors: Hannolainen Leo , Pyöriä Lari , Pratas Diogo , Lohi Jouko , Skuja Sandra , Rasa-Dzelzkaleja Santa , Murovska Modra , Hedman Klaus , Jahnukainen Timo , Perdomo Maria Fernanda
Published: May 2024

Background

The implications of inherited chromosomally integrated human herpesvirus 6 (iciHHV-6) in solid organ transplantation remain uncertain. Although this trait has been linked to unfavorable clinical outcomes, an association between viral reactivation and complications has only been conclusively established in a few cases.

Methods

We used hybrid capture sequencing for in-depth analysis of the viral sequences reconstructed from sequential liver biopsies. Moreover, we investigated viral replication through in situ hybridization (U38–U94 genes), reverse transcriptase polymerase chain reaction (U89/U90 genes), immunohistochemistry, and immunofluorescence. We also performed whole transcriptome sequencing to profile the host immune response.

Results

We report a case of reactivation of a recipient’s iciHHV-6B and subsequent infection of the graft. Using a novel approach integrating the analysis of viral and mitochondrial DNAs, we located the iciHHV-6B intragraft. We demonstrated active replication via the emergence of viral minor variants, in addition to positive viral messenger RNAs and antigen stainings in tissue sections. Furthermore, we detected significant upregulation of antiviral immune responses, arguing against immunotolerance.

Conclusions

Our analysis underscores the potential pathological impact of iciHHV-6B, emphasizing the need for monitoring reactivation in transplant recipients. Most crucially, it highlights the critical role that the host's virome can play in shaping the outcome of transplantation.
Effectiveness, safety and discontinuation rates of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in people with HIV using real-world data: a systematic review and meta-analysis
Authors: Chivite Iván , Berrocal Leire , de Lazzari Elisa , Navadeh Soodabeh , Lluis-Ganella Carla , Inciarte Alexy , de la Mora Lorena , González-Cordón Ana , Martínez-Rebollar Maria , Laguno Montserrat , Torres Berta , Blanco José Luis , Martínez Esteban , Mallolas Josep , Ambrosioni Juan
Published: May 2024

Background

The use of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) is based on the results of robust clinical trials.

Objectives

To assess the effectiveness and safety of BIC/FTC/TAF in treatment-naïve (TN) and treatment-experienced (TE) people with HIV using available real-world cohort studies.

Methods

Systematic review and meta-analysis of publications and communications identified via Boolean search in Medline, PubMed and Embase, and conference abstracts reporting retrospective real-world use of BIC/FTC/TAF, published until 31 January 2024. The primary endpoint was the proportion of TN and TE people with HIV with viral load (VL) < 50 copies/mL at 48 weeks while on treatment.

Results

Of the 38 identified publications and conference abstracts, for the present analysis we included 12 publications (comprising 792 TN and 6732 TE individuals). For the three publications including 507 TN participants reporting the primary outcome, VL suppression was 97% [95% confidence intervals (CI): 89–100]. For the nine publications including 4946 TE participants reporting the primary outcome, VL suppression was 95% (95% CI: 94–96), with suppression >93% in all studies. Total discontinuations at 48 weeks in TE individuals were 3% (95% CI: 2–5), 1% (95% CI: 0–2) due to side effects. A total of four publications with 151 TE individuals with previous presence of M184V substitution were identified, reporting a suppression rate at 48 weeks of 95% (95% CI: 88–100).

Conclusions

Real-world studies demonstrate low discontinuation rates and high rates of virologic suppression in individuals treated with BIC/FTC/TAF, both TN and TE with and without previous detection of M184V substitution.
Utilizing ChatGPT as a scientific reasoning engine to differentiate conflicting evidence and summarize challenges in controversial clinical questions
Authors: Xie Shiyao , Zhao Wenjing , Deng Guanghui , He Guohua , He Na , Lu Zhenhua , Hu Weihua , Zhao Mingming , Du Jian
Published: May 2024

Objective

Synthesizing and evaluating inconsistent medical evidence is essential in evidence-based medicine. This study aimed to employ ChatGPT as a sophisticated scientific reasoning engine to identify conflicting clinical evidence and summarize unresolved questions to inform further research.

Materials and Methods

We evaluated ChatGPT’s effectiveness in identifying conflicting evidence and investigated its principles of logical reasoning. An automated framework was developed to generate a PubMed dataset focused on controversial clinical topics. ChatGPT analyzed this dataset to identify consensus and controversy, and to formulate unsolved research questions. Expert evaluations were conducted 1) on the consensus and controversy for factual consistency, comprehensiveness, and potential harm and, 2) on the research questions for relevance, innovation, clarity, and specificity.

Results

The gpt-4-1106-preview model achieved a 90% recall rate in detecting inconsistent claim pairs within a ternary assertions setup. Notably, without explicit reasoning prompts, ChatGPT provided sound reasoning for the assertions between claims and hypotheses, based on an analysis grounded in relevance, specificity, and certainty. ChatGPT’s conclusions of consensus and controversies in clinical literature were comprehensive and factually consistent. The research questions proposed by ChatGPT received high expert ratings.

Discussion

Our experiment implies that, in evaluating the relationship between evidence and claims, ChatGPT considered more detailed information beyond a straightforward assessment of sentimental orientation. This ability to process intricate information and conduct scientific reasoning regarding sentiment is noteworthy, particularly as this pattern emerged without explicit guidance or directives in prompts, highlighting ChatGPT’s inherent logical reasoning capabilities.

Conclusion

This study demonstrated ChatGPT’s capacity to evaluate and interpret scientific claims. Such proficiency can be generalized to broader clinical research literature. ChatGPT effectively aids in facilitating clinical studies by proposing unresolved challenges based on analysis of existing studies. However, caution is advised as ChatGPT’s outputs are inferences drawn from the input literature and could be harmful to clinical practice.
An example of leveraging AI for documentation: ChatGPT-generated nursing care plan for an older adult with lung cancer
Authors: Dos Santos Fabiana C , Johnson Lisa G , Madandola Olatunde O , Priola Karen J B , Yao Yingwei , Macieira Tamara G R , Keenan Gail M
Published: May 2024

Objective

Our article demonstrates the effectiveness of using a validated framework to create a ChatGPT prompt that generates valid nursing care plan suggestions for one hypothetical older patient with lung cancer.

Method

This study describes the methodology for creating ChatGPT prompts that generate consistent care plan suggestions and its application for a lung cancer case scenario. After entering a nursing assessment of the patient's condition into ChatGPT, we asked it to generate care plan suggestions. Subsequently, we assessed the quality of the care plans produced by ChatGPT.

Results

While not all the suggested care plan terms (11 out of 16) utilized standardized nursing terminology, the ChatGPT-generated care plan closely matched the gold standard in scope and nature, correctly prioritizing oxygenation and ventilation needs.

Conclusion

Using a validated framework prompt to generate nursing care plan suggestions with ChatGPT demonstrates its potential value as a decision support tool for optimizing cancer care documentation.
Ameliorative Potential of Bone Marrow–Derived Mesenchymal Stem Cells Versus Prednisolone in a Rat Model of Lung Fibrosis: A Histological, Immunohistochemical, and Biochemical Study
Authors: Shalaby Amany Mohamed , Hassan Shaimaa Mohamed Abdelfattah , Abdelnour Hanim Magdy , Alnasser Sulaiman Mohammed , Alorini Mohammed , Jaber Fatima A , Alabiad Mohamed Ali , Abdullatif Asmaa , Elshaer Mohamed Mahmoud Abdelrahim , Aziz Seham Ahmed Mohammed Abdel , Abdelghany Eman M A
Published: May 2024

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease of unknown origin with limited treatment options and poor prognosis. The encouraging findings from preclinical investigations utilizing mesenchymal stem cells (MSCs) indicated that they could serve as a promising therapeutic alternative for managing chronic lung conditions, such as IPF. The objective of this study was to compare the efficiency of bone marrow–derived MSCs (BM-MSCs) versus prednisolone, the standard anti-inflammatory medication, in rats with bleomycin (BLM)-induced lung fibrosis. Four groups were created: a control group, a BLM group, a prednisolone-treated group, and a BM-MSCs-treated group. To induce lung fibrosis, 5 mg/kg of BLM was administered intratracheally. BLM significantly increased serum levels of pro-inflammatory cytokines and oxidative stress markers. The disturbed lung structure was also revealed by light and transmission electron microscopic studies. Upregulation in the immune expression of alpha-smooth muscle actin, transforming growth factor beta-1, and Bax was demonstrated. Interestingly, all findings significantly regressed on treatment with prednisolone and BM-MSCs. However, treatment with BM-MSCs showed better results than with prednisolone. In conclusion, BM-MSCs could be a promising approach for managing lung fibrosis.
Connecting Species-Specific Extents of Genome Reduction in Mitochondria and Plastids
Authors: Giannakis Konstantinos , Richards Luke , Dauda Kazeem A , Johnston Iain G
Published: May 2024

Mitochondria and plastids have both dramatically reduced their genomes since the endosymbiotic events that created them. The similarities and differences in the evolution of the two organelle genome types have been the target of discussion and investigation for decades. Ongoing work has suggested that similar mechanisms may modulate the reductive evolution of the two organelles in a given species, but quantitative data and statistical analyses exploring this picture remain limited outside of some specific cases like parasitism. Here, we use cross-eukaryote organelle genome data to explore evidence for coevolution of mitochondrial and plastid genome reduction. Controlling for differences between clades and pseudoreplication due to relatedness, we find that extents of mtDNA and ptDNA gene retention are related to each other across taxa, in a generally positive correlation that appears to differ quantitatively across eukaryotes, for example, between algal and nonalgal species. We find limited evidence for coevolution of specific mtDNA and ptDNA gene pairs, suggesting that the similarities between the two organelle types may be due mainly to independent responses to consistent evolutionary drivers.
Influences of advanced age in rheumatoid arthritis: A multicentre ultrasonography cohort study
Authors: Kawahara Chieko , Fukui Shoichi , Michitsuji Tohru , Nishino Ayako , Endo Yushiro , Shimizu Toshimasa , Umeda Masataka , Sumiyoshi Remi , Koga Tomohiro , Iwamoto Naoki , Origuchi Tomoki , Ueki Yukitaka , Eiraku Nobutaka , Suzuki Takahisa , Okada Akitomo , Matsuoka Naoki , Takaoka Hirokazu , Hamada Hiroaki , Tsuru Tomomi , Arinobu Yojiro , Hidaka Toshihiko , Fujikawa Keita , Yoshitama Tamami , Tada Yoshifumi , Ohtsubo Hideo , Ishizaki Jun , Asano Tomoyuki , Kawakami Atsushi , Kawashiri Shin-ya
Published: May 2024

Objectives

We aimed to evaluate the effects of age on clinical characteristics and outcomes in biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD)-naïve patients with rheumatoid arthritis (RA).

Methods

We analysed the cases of 234 Japanese b/tsDMARD-naïve RA patients who underwent b/tsDMARD treatment in a multicentre ultrasound prospective observational cohort. We compared the clinical characteristics at baseline and outcomes at 12 months between those aged ≥60 years and those <60 years.

Results

Compared to the <60-year-old group (n = 78), the ≥60-year-old group (n = 156) had higher inflammatory marker values and ultrasound combined scores, especially wrist joints, at baseline. Age at baseline positively correlated significantly with the ultrasound scores at baseline; however, age was not a significant variable by the multiple regression analysis. The patients treated with different MOAs in the ≥60-year-old group had comparable outcomes and multiple regression analysis revealed that mechanism of action (MOA) was not a significant contributor to the Clinical Disease Activity Index at 12 months.

Conclusions

RA patients with advanced age demonstrated distinctive clinical characteristics. The MOAs were not associated with clinical outcomes and ultrasound outcomes in RA patients with advanced age.
Sinonasal cancer incidence in Lombardy, Italy, 2008–20
Authors: Consonni D , Stoppa G , Binazzi A , Dallari B , Stella S , Rugarli S , Trobbiani C , Biggeri A , Catelan D , Mensi C
Published: May 2024

Background

Epithelial sinonasal cancers (SNC) are rare tumours with recognized associations with known/suspected occupational carcinogens (wood/leather dust, nickel/chromium compounds and formaldehyde). In Italy, a national SNC registry organized as a network of regional registries was established by law in 2008.

Aims

To describe SNC time trends, occupational exposures and geographical distribution in Lombardy, North-West Italy, based on population registry data (2008–20).

Methods

The Lombardy SNC Registry records epithelial SNCs using various sources. Interviews to collect occupational history are performed using a standardized questionnaire. Using several standard populations, we calculated yearly crude and age-standardized rates (ASRs per 100,000 person-years). Standardized incidence ratios (SIR) at municipality level were calculated, and Bayesian models were fitted to produce smoothed SIR maps.

Results

We recorded 827 cases (553 men, 274 women). Crude (world standardized) ASRs were 0.9 (0.4) in men and 0.4 (0.2) in women, with no time trends. Interviews were obtained for 485 (88%) men and 223 (81%) women. Among men, 217 (45%) had been exposed to occupational carcinogens (wood/leather dust: 150/65 cases, 31%/13%), while only 36 women (16%) were exposed. Among 201 men with adenocarcinoma, exposure to wood/leather dust occurred in 103/50 cases (75%/50%). Areas with elevated SIRs associated with leather dust were found in the Western areas. Exposure to wood dust was more widespread.

Conclusions

This study found a high frequency of occupational exposures (wood and leather dust), particularly in men with SNC. Employment in shoe industries clustered in the Western part, while work in furniture industries was less spatially structured.
Quantifying US air pollution policy: How political and regional factors influence pollutant mitigation
Authors: Zhang Guoxing , Chen Zhanglei , Li Jiexun , Su Bin , Gao Yang , Yu Lean
Published: May 2024

Air pollution control in the United States has evolved into a comprehensive policy system spanning from the federal to the state level over time. A unified quantitative analysis of policy intensity can shed light on the policy evolution across different levels, the influence of partisan and regional factors on policy, and the relationships with emissions of major pollutants. By harnessing the policy text of the Clean Air Act (CAA) at the federal level and State Implementation Plans (SIPs) at the state governments (1955–2020), we deployed a Natural Language Processing approach to define a policy intensity index to systematically quantify the US air policy landscape. Our findings highlight that the 1970 CAA amendment carries the most vigorous intensity as it established a holistic control system for the first time. Subsequent years witnessed a general trend of partisan polarization, eventually leading to a graduate convergence between red and blue states. Blue states demonstrated a closer alignment with federal directives and a superior efficacy in pollutant reduction. Regionally, the Northeast displays the highest overall policy intensity, and the West exhibits the highest coordination with the federal benchmarks, making these regions outperform others in air pollution control. Our study not only discusses policy implications for air pollutant reductions considering partisan and regional differences but also provides a novel measurement tool to quantify policies for assessing disparities and synergies.
DexDesign: an OSPREY-based algorithm for designing de novo D-peptide inhibitors
Authors: Guerin Nathan , Childs Henry , Zhou Pei , Donald Bruce R
Published: May 2024

With over 270 unique occurrences in the human genome, peptide-recognizing PDZ domains play a central role in modulating polarization, signaling, and trafficking pathways. Mutations in PDZ domains lead to diseases such as cancer and cystic fibrosis, making PDZ domains attractive targets for therapeutic intervention. D-peptide inhibitors offer unique advantages as therapeutics, including increased metabolic stability and low immunogenicity. Here, we introduce DexDesign, a novel OSPREY-based algorithm for computationally designing de novo D-peptide inhibitors. DexDesign leverages three novel techniques that are broadly applicable to computational protein design: the Minimum Flexible Set, K*-based Mutational Scan, and Inverse Alanine Scan. We apply these techniques and DexDesign to generate novel D-peptide inhibitors of two biomedically important PDZ domain targets: CAL and MAST2. We introduce a framework for analyzing de novo peptides—evaluation along a replication/restitution axis—and apply it to the DexDesign-generated D-peptides. Notably, the peptides we generated are predicted to bind their targets tighter than their targets' endogenous ligands, validating the peptides' potential as lead inhibitors. We also provide an implementation of DexDesign in the free and open source computational protein design software OSPREY.
Do lead (Pb) content of lipsticks expose a health risk to children? A risk assessment study
Authors: Öztaş Demir Mesut , Ulutaş Onur Kenan , Berkkan Aysel
Published: May 2024

Background

Lead (Pb) content in lipsticks and potential life-long exposure of which might cause severe effects in consumers are an important concern for public. Thus, studies emphasize that lead exposure has no safe levels.

Methods

From 10 different brands, in total, 25 solid, gloss and creamy lipsticks are deployed from Turkish markets that are also categorized in two different price ranges. In order to evaluate the blood Pb levels in children, the United States Environmental Protection Agency’s ‘Exposure Uptake Biokinetic Model’ is utilized. To assess the health risk of chronic usage both for children and adults, oral daily systemic exposure levels are calculated with the worst-case scenario and are compared with Maximum Allowable Dose Level for lipsticks. For lifetime risk assessment, exposure is assumed to start by age 7, and four different exposure scenarios have been deployed.

Results

The mean lead content of lipsticks shows significant statistical differences between the high- and low-priced lipstick groups. Daily level and total risk for lifetime Pb exposure from deployed lipsticks are below the acceptable risk levels but long-worn usage of products with routine monitoring of metal content is crucial for sensitive and unintended exposure groups.
Investigating incidence of and factors associated with SARS-CoV-2 infection over a nine-month period in a highly-vaccinated healthcare worker cohort
Authors: Townsend Liam , Marron Louise , O’Brien Katie , Walsh Cathal , Domegan Lisa , McGrath Jonathan , Kenny Claire ,   PRECISE Study Steering Group, Fleming Catherine , Bergin Colm
Published: May 2024

Background

Healthcare workers (HCWs) are at increased risk of SARS-CoV-2 infection. This risk persists despite the implementation of mitigating factors, including vaccination. The ongoing impact of incident SARS-CoV-2 infection and symptomatic COVID-19 disease in vaccinated HCWs is poorly understood.

Aim

We aimed to describe the epidemiology of incident SARS-CoV-2 infections, as well as investigating the serological, clinical and demographic factors associated with developing infection.

Design

This was a multi-centre prospective longitudinal study followed a HCW cohort over a nine-month period.

Methods

Spike and nucleocapsid SARS-CoV-2 antibodies were measured at enrolment. Vaccination status, demographics and medical history were collated. Incident infection over the study period was recorded. Multivariable regression models investigated factors associated with nucleocapsid antibody status, incident infection and symptomatic infection.

Results

About 1260 participants took part, of whom n = 1006 were anti-nucleocapsid antibody positive. Negative anti-nucleocapsid antibody was associated with older age and having a known SARS-CoV-2 acquisition risk. There were n = 274 (22%) incident infections, with n = 225 (87%) diagnosed using antigen tests. Incident infections were associated with lower anti-nucleocapsid titres, increased time since previous SARS-CoV-2 infection, and having a known acquisition risk, but were not associated with vaccination status.

Conclusions

This study demonstrates a high rate of incident SARS-CoV-2 infection amongst HCWs, despite broad vaccine coverage. There is a shift in diagnostics, from PCR to antigen testing. We identify at-risk groups for incident infection, and these should continue be targeted as part of risk reduction campaigns. Vaccination status and prior infection status alone are not surrogates for protection.
An inductive method for separable deformations
Authors: Amsalem Ariel , Ginosar Yuval
Published: May 2024

The Donald–Flanigan conjecture asserts that any group algebra of a finite group has a separable deformation. We apply an inductive method to deform group algebras from deformations of normal subgroup algebras, establishing an infinite family of metacyclic groups which fulfill the conjecture.
Native myocardial T1 and right ventricular size by CMR predict outcome in systemic sclerosis-associated pulmonary hypertension
Authors: Knight Daniel S , Virsinskaite Ruta , Karia Nina , Cole Alice R , Maclean Rory H , Brown James T , Patel Rishi K , Razvi Yousuf , Venneri Lucia , Kotecha Tushar , Martinez-Naharro Ana , Kellman Peter , Scott-Russell Ann M , Schreiber Benjamin E , Ong Voon H , Denton Christopher P , Fontana Marianna , Coghlan J Gerry , Muthurangu Vivek
Published: May 2024

Objectives

Measures of right heart size and function are prognostic in systemic sclerosis-associated pulmonary hypertension (SSc-PH), but the importance of myocardial tissue characterisation remains unclear. We aimed to investigate the predictive potential and interaction of cardiovascular magnetic resonance (CMR) myocardial tissue characterisation and right heart size and function in SSc-PH.

Methods

A retrospective, single-centre, observational study of 148 SSc-PH patients confirmed by right heart catheterization who underwent clinically indicated CMR including native myocardial T1 and T2 mapping from 2016 to 2023 was performed.

Results

Sixty-six (45%) patients died during follow-up (median 3.5 years, range 0.1–7.3). Patients who died were older (65 vs 60 years, P = 0.035) with more dilated (P < 0.001), hypertrophied (P = 0.013) and impaired (P < 0.001) right ventricles, more dilated right atria (P = 0.043) and higher native myocardial T1 (P < 0.001).

After adjustment for age, indexed right ventricular end-systolic volume (RVESVi, P = 0.0023) and native T1 (P = 0.0024) were independent predictors of all-cause mortality. Both RVESVi and native T1 remained independently predictive after adjusting for age and PH subtype (RVESVi P < 0.001, T1 P = 0.0056). Optimal prognostic thresholds for RVESVi and native T1 were ≤38 mL/m2 and ≤1119 ms, respectively (P < 0.001). Patients with RVESVi ≤ 38 mL/m2 and native T1 ≤ 1119 ms had significantly better outcomes than all other combinations (P < 0.001). Furthermore, patients with RVESVi > 38mL/m2 and native T1 ≤ 1119 ms had significantly better survival than patients with RVESVi > 38mL/m2 and native T1 > 1119ms (P = 0.017).

Conclusion

We identified prognostically relevant CMR metrics and thresholds for patients with SSc-PH. Assessing myocardial tissue characterisation alongside right ventricular function confers added value in SSc-PH and may represent an additional treatment target.
Transorbital ultrasound in the diagnosis of giant cell arteritis
Authors: Petzinna Simon M , Burg Lara C , Bauer Claus-Juergen , Karakostas Pantelis , Terheyden Jan H , Behning Charlotte , Holz Frank G , Brossart Peter , Finger Robert P , Schäfer Valentin S
Published: May 2024

Objectives

The objective of this study was to prospectively evaluate the diagnostic efficacy of transorbital ultrasound (TOS) in patients newly diagnosed with giant cell arteritis (GCA), presenting with visual symptoms.

Methods

Patients with newly diagnosed, untreated GCA were examined using TOS, assessing central retinal artery flow velocity [peak systolic velocity (PSV), end-diastolic velocity (EDV), resistance index (RI)], and optic nerve diameter (OND). Vascular ultrasound was conducted to evaluate the superficial temporal arteries, their branches, facial, axillary, carotid, and vertebral arteries.

Results

We enrolled 54 GCA patients, 27 with visual symptoms, and 27 healthy controls. Eyes of GCA patients with visual symptoms demonstrated significantly lower PSV and EDV (PSV: β = −1.91; P = 0.029; EDV: β = −0.57; P = 0.032) and significantly elevated OND (β = 0.79; P = 0.003) compared with controls. RI did not significantly differ from controls (β = −0.06, P = 0.129). Vascular ultrasound identified an average of 8.7 (SD ± 2.8) pathological vessels per GCA patient. A significant negative association was observed between the number of affected vessels and both PSV (P = 0.048) and EDV (P = 0.040). No association was found with RI (P = 0.249), while a positive significant association was noted with OND (P < 0.001).

Conclusions

This study pioneers the application of TOS to assess structural eye changes in newly diagnosed, untreated GCA patients with visual symptoms. Our findings suggest reduced central retinal artery flow and increased optic nerve diameter as potential biomarkers for serious ocular involvement in GCA. The detected association between internal and external carotid artery involvement indicates a common pathophysiological mechanism underlying systemic and ocular manifestations of GCA.
The end of polarization? Evolutions of the distribution of employment across couples in Europe over the past 40 years
Authors: Paugam Guillaume
Published: May 2024

This article revisits the claim that heterosexual couple employment participation has increasingly been polarizing in Europe between dual-jobless and dual-earning. Studying twenty-seven European countries over 4 decades, it finds that polarization has increased, but at a clearly decreasing rate. Polarization rose in the 1980s/1990s, as women joining employment then were disproportionately likely to have a male partner also employed. It has slowed-down since, as rising female employment eventually started materializing into substantial rates of female-single-earning. The article explores different potential factors behind this shift. At the macro-level, the sectoral transformation of economies and the 2008 crisis have had lasting impacts on couple employment. At the couple level, partnered women have become more educated than partnered men, fuelling the rise in female-single-earning. Amongst disadvantaged couples, dual-worklessness has decreased, but is being replaced by the clustering of non-standard employment in couples.
Japan: Treatment of foreign organizations (including private foundations) and trusts in Japan
Authors: Sakai Hitomi
Published: May 2024

The article discusses the treatment of foreign organizations and trusts from the Japanese legal and tax perspectives, with reference to the 2015 decision of the Supreme Court that a limited partnership formed under the laws of the state of Delaware constitutes a corporation for Japanese tax purposes. This judgment is the first and only decision from the Supreme Court that provides the criteria for determining whether an organization established under foreign law is a corporation for Japanese tax purposes. The article assesses the application of these criteria and provides a guide for analyzing the Japanese tax implications of foreign organizations.
Chitosan-TPP encapsulated quercetin nanoparticles: amplified protection mechanisms unveiled against Ethion-induced developmental toxicity through comprehensive in-vivo and in-silico elucidation
Authors: Ranjith D , Telang A G , Subhadra Sandhya , Kamothi Dhaval J , Madhu C L , Kumar Dinesh
Published: May 2024

Aim

The study investigated Ethion-induced developmental toxicity in Wistar albino rats and the potential ameliorative effects of quercetin and nano-quercetin co-administration. Further, In-silico docking of Ethion and quercetin with MCL-1 was conducted.

Methodology

Quercetin nanoparticles were synthesized by ionic-gelation method. The encapsulated quercetin nanoparticles were characterized for Zeta size, UV-Vis spectroscopy, encapsulation efficiency, and TEM studies. Male rats were administered Ethion (high/low dose), quercetin, and nano-quercetin alone or in combination for 60 days. Female rats were introduced for mating on the 61st day, and pregnant females were observed for 20 gestational days. On GD 20, rats were sacrificed and evaluated for body/organ weight, reproductive indices, fetal morphology, skeletal, and visceral deformities.In silico binding energies of ethion and quercetin with MCL-1 were determined.

Results

Nanoparticle size was 363.2 ± 1.23 nm on day 0 and 385.63 ± 1.53 nm on day 60, with PDI of 0.247 and charge of 22.9 mV. Absorbance maxima were at 374 nm, with encapsulation efficacy of 85.16 ± 0.33%. EHD male crossed females showed decreased body/organ weights, reduced fertility, hematoma, cleft palate, tail curling, and absence of extremity. Nano-quercetin co-administration normalized parameters comparable to controls. Both Ethion and quercetin interacted with MCL-1, with quercetin exhibiting stronger binding energy.

Conclusion

Nano-quercetin demonstrated stronger antioxidant properties than quercetin, counteracting ethion-induced maternal/fetal abnormalities.
Population Pharmacokinetic Modeling of Unbound Meropenem in Patients Undergoing Continuous Renal Replacement Therapy: An Observational Cohort Study
Authors: Oda Kazutaka , Jono Hirofumi , Kamohara Hidenobu , Saito Hideyuki
Published: May 2024

Background:

The most effective dosing strategy of meropenem for patients undergoing continuous renal replacement therapy (CRRT) remains uncertain. This study aimed to analyze the population pharmacokinetics (popPKs) of unbound meropenem and establish an appropriate dosing approach.

Methods:

This prospective study involved 19 patients for the development of a popPK model and an additional 10 for its validation. Ethical approval was obtained.

Results:

The clearance of unbound meropenem was influenced by the sequential organ failure assessment (SOFA) score [=2.22 × (SOFA score/12)^1.88] and the effluent flow rate from the CRRT device, with an interindividual variability of 44.5%. The volume of distribution was affected by the simplified acute physiology score II [=23.1 × (simplified acute physiology score II/52)^1.54]. Monte Carlo simulations suggested meropenem doses ranging from 1.0 to 3.0 g/d using continuous infusion to achieve a target time above the 4 times of minimum inhibitory concentration of the unbound form (%fT>4×MIC) of 100% for definitive therapy. For empirical therapy, a dose of 1.0 g/d using continuous infusion was recommended to target %fT>MIC of 100%.

Conclusions:

This study developed a popPK model for unbound meropenem in patients undergoing CRRT and formulated dosing guidelines.

Clinical trial registration:

UMIN000024321.
Post–Penetrating Keratoplasty Assessment of Endothelial Function With a Scleral Lens Challenge
Authors: Bernhisel Ashlie A. , Nau Cherie B. , Schornack Muriel M.
Published: May 2024

Patients who have undergone penetrating keratoplasty may have corneal edema because of endothelial cell dysfunction. Scleral lens wear may exacerbate edema, particularly if lens fit is suboptimal. Distinguishing between edema because of inherent endothelial cell dysfunction and swelling because of scleral lens–related hypoxia can be challenging. It is necessary, however, to identify the most likely cause of increased corneal thickness to determine whether the patient simply needs refitting for a different lens design or needs additional surgical intervention. This case report describes the utility of corneal tomographic imaging before and after scleral lens wear both to estimate endothelial cell function and to direct decisions when designing a scleral lens for a post-transplant eye.
Patchy Hair Loss
Authors: Berlin Brittany L. , Sarro Robert A.
Published: May 2024

A 9-year-old boy was found to have new-onset hair loss on his scalp, which has worsened over the last 6 months. Readers will be asked to identify the correct diagnosis based on history and clinical presentation. The purpose of this case was to improve diagnostic skills to properly recognize this condition and provide the appropriate treatment.
Ambulatory Quality Improvement Despite COVID-19: Blueprint for a Successful System for Continuous Improvement
Authors: VanBuren Anne H. , Montgomery Tricia M. , McConaghy John R. , Lawrence Jeffrey , Taj-Schaal Nazhat , Unger Melissa , Rogers Nate R.
Published: May 2024

In this article, we describe our experience developing and implementing a multipronged approach to improve performance across a strategic subset of quality measures within primary care. Detailed techniques include data visualization and analytics, process reengineering, team engagement, visual project management, continuous improvement methods and training, and incentives and recognition. We achieved positive change across 12 high priority measures which we deemed the “High Value Framework (HVF)” by fostering a collaborative, nonpunitive, problem-solving culture. We focused on measures that had the greatest potential for impact from a clinical, reimbursement, and reputational perspective. More importantly, we sustained gains despite the challenges posed by the COVID-19 pandemic, thereby demonstrating programmatic resilience and high process reliability. This systematic approach serves as a practical blueprint for other healthcare entities seeking to navigate the complexities of quality improvement in a dynamic environment. The model provides a strategic framework for prioritizing and standardizing quality measures, effectively engaging stakeholders, and managing organizational change. Our model emerged from a need to address real-world operational challenges, rather than as an academic or theoretical exercise, and was developed independently of existing literature on measure prioritization and standardization at the time of its inception.
A Roadmap to Cultivating a Culture of Belonging for Learners in Physical Therapy Education
Authors: Magee Julian , Brown Dawn , Woods LaDarius , Portee Charlene
Published: May 2024

A sense of belonging guides learners toward connections, acceptance, and a sense of being valued and, ultimately, academic success. However, a recent national study revealed that learners from racially and ethnically minoritized group expressed less satisfaction with their Doctor of Physical Therapy education and less agreement that their programs fostered psychological well-being. This roadmap for belonging is specifically designed for learners of color but can be generalized to all students considering the intersectionality of historically dominant and nondominant sociocultural identities. Essential steps include an assessment of who is in the classroom, identifying resources to support students, and creating accountability and sustainability metrics. By following this belonging roadmap, physical therapy educators can work toward cultivating a greater sense of belonging for learners in academic spaces.
Paroxysmal sympathetic hyperexcitability after brain injury: A clinical analysis of case series
Authors: Li Xingru , Yang Xinchen , Yu Tao , Zhang Tiqiang , Tang Yun
Published: May 2024

Background:

Paroxysmal sympathetic hyperexcitability (PSH) is a group of complex syndromes with various etiologies. Previous studies were limited to the description of traumatic brain injury (TBI), and the description of PSH after other types of brain injury was rare. We explored the clinical features, treatment, and prognosis of PSH after various types of brain injuries.

Methods:

Patients admitted to the neurosurgery intensive care unit with PSH after brain injury from July 2019 to December 2022 were included. Demographic data, clinical manifestations, drug therapy, and disease prognosis were retrospectively collected and analyzed.

Results:

Fifteen male and 9 female patients with PSH after brain injury were selected. TBI was most likely to cause PSH (66.7%), followed by spontaneous intracerebral hemorrhage (25%). Glasgow coma scale scores of 19 patients (79.2%) were lower than 8 and 14 patients (58.3%) underwent tracheotomy. Electroencephalogram monitoring was performed in 12 individuals, none of which showed epileptic waves. Clinical symptom scale showed mild symptoms in 17 cases (70.8%). Almost all patients were administered a combination of drugs. After follow-up, most patients had a poor prognosis and 2 (8.3%) died after discharge.

Conclusion:

The etiology of PSH is complex. TBI may be the most common cause of PSH. Non-TBI may also be an important cause of PSH. Therefore, early identification, prevention and diagnosis are helpful for determining the prognosis and outcome of the disease.
Function of NEK2 in clear cell renal cell carcinoma and its effect on the tumor microenvironment
Authors: Tang Peng , Zheng Gangfu , Xu Congcong , Yu Nengfeng , Du Jiaqi , Hu Liqian , Zhou Zhan , Zheng Yichun
Published: May 2024

Background:

Previous studies have revealed the critical functions of NEK2 in controlling the cell cycle which is linked to poor prognosis in multiple tumor types, but less research has been devoted to clear cell renal cell carcinoma (ccRCC).

Methods:

We downloaded clinical data from the gene expression omnibus (GEO) and TCGA databases together with transcriptional and mutational datasets. Strongly coexpressed genes with NEK2 were extracted from TCGA-KIRC cohort, and were submitted to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for functional analyses. According to NEK2 levels, the survival status, mutational characteristics, response to immunotherapy and sensitivity to drugs of the patients were studied. The potential correlations between NEK2 levels and immune cell state as well as immune cell infiltration were examined using the GEPIA, TIMER and TISIDB databases. Double immunofluorescence (IF) was performed to identify the NEK2 overexpression and relationship with CD8 in ccRCC.

Results:

The NEK2 gene was overexpressed and would enhance the nuclear division and cell cycle activities in ccRCC. ccRCC patients with high NEK2 expression had worse clinical outcomes, higher mutation burden and better therapeutic response. Moreover, NEK2 gene overexpression was positively related to various immune cell marker sets, which was also proved by validation cohort, and more infiltration of various immune cells.

Conclusion:

ccRCC patients with NEK2 high expression have a poorer prognosis than those with NEK2 low expression, resulting from its function of promoting proliferation, accompanied by increased infiltration of CD8 + T cells and Tregs and T-cell exhaustion and will respond better to proper treatments.
Distinct characteristics of distant metastasis in early-onset gastric cancer patients compared to late-onset patients: An observational study
Authors: Wu Feng , Wu Shuang , Shuai Shujie
Published: May 2024

Presently, there is limited understanding of the features of distant metastasis in early-onset gastric cancer (GC). To explore these disparities, a retrospective study utilizing the Surveillance, Epidemiology, and End Results (SEER) database was undertaken. The SEER database was utilized to extract patient data, and multivariate logistic regression analysis was employed to identify the risk factors associated with distant metastasis and liver metastasis. Propensity score matching (PSM) was used to compare the occurrence of liver metastasis among patients based on their age at diagnosis. The study included 2684 early-onset GC patients and 33,289 late-onset GC patients. Preliminary data analysis indicated that early-onset GC patients exhibited more aggressive characteristics such as poor cell differentiation, advanced T stage, and a higher incidence of distant metastasis, excluding liver metastasis. Multivariate logistic regression analysis identified younger age as an independent risk factor for distant metastasis, along with T stage, lymph node metastasis (LNM), and tumor size (>3 cm). Another regression analysis revealed that younger age, diffuse type, and female gender were protective factors against liver metastasis. Through PSM, 3276 early-onset GC patients were matched with an equal number of late-onset GC patients, revealing that patients with early-onset GC had fewer instances of liver metastasis but a higher prevalence of distant metastasis. Our findings suggest that early-onset serves as a protective factor against liver metastasis in GC, while it poses a risk for distant metastasis, likely influenced by the increased prevalence of diffuse-type GC in early-onset patients.