bluuebunny/crossref_metadata_2025 huggingface dataset:
Has the COVID-19 pandemic changed existing patterns of non-COVID-19 health care utilization? A retrospective analysis of six regions in Europe
Authors: Aldridge Sarah J , Schmidt Andrea E , Thißen Martin , Bernal-Delgado Enrique , Estupiñán-Romero Francisco , González-Galindo Javier , Dolanski-Aghamanoukjan Lorenz , Mathis-Edenhofer Stefan , Buble Tamara , Križ Klea , Vuković Jakov , Palmieri Luigi , Unim Brigid , Meulman Iris , Owen Rhiannon K , Lyons Ronan A
Published: October 2023

Background

Resilience of national health systems in Europe remains a major concern in times of multiple crises and as more evidence is emerging relating to the indirect effects of the COVID-19 pandemic on health care utilization (HCU), resulting from de-prioritization of regular, non-pandemic healthcare services. Most extant studies focus on regional, disease specific or early pandemic HCU creating difficulties in comparing across multiple countries. We provide a comparatively broad definition of HCU across multiple countries, with potential to expand across regions and timeframes.

Methods

Using a cross-country federated research infrastructure (FRI), we examined HCU for acute cardiovascular events, elective surgeries and serious trauma. Aggregated data were used in forecast modelling to identify changes from predicted European age-standardized counts via fitted regressions (2017–19), compared against post-pandemic data.

Results

We found that elective surgeries were most affected, universally falling below predicted levels in 2020. For cardiovascular HCU, we found lower-than-expected cases in every region for heart attacks and displayed large sex differences. Serious trauma was the least impacted by the COVID-19 pandemic.

Conclusion

The strength of this study comes from the use of the European Population Health Information Research Infrastructure’s (PHIRI) FRI, allowing for rapid analysis of regional differences to assess indirect impacts of events such as pandemics. There are marked differences in the capacity of services to return to normal in terms of elective surgery; additionally, we found considerable differences between men and women which requires further research on potential sex or gender patterns of HCU during crises.
Developing a Structural Complexity Index for Oriental Beech Forests in Northern Iran
Authors: Sefidi Kiomars , Copenheaver Carolyn A , Thom Dominik , Felbermeier Bernhard
Published: October 2023

The structural complexity index (SCI) has become an important metric for forest managers to monitor ecosystem services and conservation value in a wide variety of forest types. In this study, we developed an SCI for an unmanaged mixed Fagus orientalis Lipsky forest in northern Iran, which incorporated structural information specific to mature and old-growth forests. Our results showed that we were able to develop an SCI for this forest that would assist managers to make conservation decisions in a forest where large overstory trees and small understory trees are equally important. The SCI was significantly positively correlated with the density of five minor tree species (Acer velutinum Boiss., Acer cappadocicum Gled., Tilia begoniifolia Chun & H.D. Wong, Quercus castaneifolia C.A. Mey., and Prunus avium L.) and the density of large ([50 cm <  diameter at breast height {DBH} < 75 cm]) and very large (DBH > 75 cm) overstory trees. The SCI remains a highly flexible tool for forest conservation and decision making and may assist with decisions about forest management in response to climate change and shifting disturbance regimes.

Study Implications: Forest managers have begun to use the structural complexity index (SCI) to assess the successful achievement of conservation management objectives. In many mature, mixed-species forests, large trees, minor species, and understory tree species are important structural components. In this study, we demonstrate that reduction of the minimum diameter used for sampling trees and careful selection of the variables used to calculate SCI results in a valuable metric for making conservation decisions. The advantage of SCI as a forest decision tool is that forest managers are able to adjust the inputs used to calculate SCI to reflect specific management objectives or monitoring goals.
Metabolomic analysis of Drosophila melanogaster larvae lacking pyruvate kinase
Authors: Heidarian Yasaman , Tourigny Jason P , Fasteen Tess D , Mahmoudzadeh Nader H , Hurlburt Alexander J , Nemkov Travis , Reisz Julie A , D’Alessandro Angelo , Tennessen Jason M
Published: October 2023

Pyruvate kinase (Pyk) is a rate-limiting enzyme that catalyzes the final metabolic reaction in glycolysis. The importance of this enzyme, however, extends far beyond ATP production, as Pyk is also known to regulate tissue growth, cell proliferation, and development. Studies of this enzyme in Drosophila melanogaster are complicated by the fact that the fly genome encodes 6 Pyk paralogs whose functions remain poorly defined. To address this issue, we used sequence distance and phylogenetic approaches to demonstrate that the gene Pyk encodes the enzyme most similar to the mammalian Pyk orthologs, while the other 5 Drosophila Pyk paralogs have significantly diverged from the canonical enzyme. Consistent with this observation, metabolomic studies of 2 different Pyk mutant strains revealed that larvae lacking Pyk exhibit a severe block in glycolysis, with a buildup of glycolytic intermediates upstream of pyruvate. However, our analysis also unexpectedly reveals that pyruvate levels are unchanged in Pyk mutants, indicating that larval metabolism maintains pyruvate pool size despite severe metabolic limitations. Consistent with our metabolomic findings, a complementary RNA-seq analysis revealed that genes involved in lipid metabolism and protease activity are elevated in Pyk mutants, again indicating that loss of this glycolytic enzyme induces compensatory changes in other aspects of metabolism. Overall, our study provides both insight into how Drosophila larval metabolism adapts to disruption of glycolytic metabolism as well as immediate clinical relevance, considering that Pyk deficiency is the most common congenital enzymatic defect in humans.
The family meal, a ritual frozen in time; an Australian grounded theory study
Authors: Middleton Georgia , Golley Rebecca K , Patterson Karen A , Coveney John
Published: October 2023

Family meals are recognized as an opportunity to promote the health of families. Popular discourse posits that changes to contemporary family life have made family meals harder to achieve and promotion of the ‘traditional’ family meal may be adding pressures to contemporary families. While research has been conducted on family meals over the last three decades, there is no explicit investigation of the experiences and practices of family meals over this time. Understanding the evolution of family meal practices across time is important for developing achievable expectations in relation to this ritual. Qualitative interviews were conducted with a diverse population of South Australian parents in the 1990s (n = 32) and with a separate population of parents in 2020 (n = 22) to gather their experiences of family meal practices. A comparative analysis, informed by grounded theory, was undertaken to identify similarities and differences in experiences across these two time periods. The results indicated stability in many family meal experiences across time, particularly in their value and significance in family life. Negotiations balancing time, cost, food preferences and responsibility persisted. The stability of family meal values and practices is important to consider when making recommendations, designing interventions and creating services targeting the family meal.
Lived experience of diet-related health education in type 2 diabetes and hypertension comorbidity in The Gambia
Authors: Touray Tahir Ahmad , Woodall James , Warwick-Booth Louise
Published: October 2023

The incidence and prevalence of type 2 diabetes mellitus (T2DM) and hypertension (and their comorbidity) have been increasing in sub-Saharan Africa, including The Gambia. Diet is a critical driver of these public health problems, and diet-related health education is a major strategy employed for their prevention and management. The aim of this paper is to explore the lived experiences of diet-related health education among individuals with comorbid type 2 diabetes and hypertension in Serrekunda, The Gambia, a subject hitherto unexplored in the country. The study employed a qualitative (interpretivist) methodology. Thirty-two interviews were conducted with 18 participants, with most participating in two interviews at separate time-points between November 2018 and July 2019. In addition to participant validation, the two points in time interviews elicited more depth and provided rich data. The data were analysed using Braun and Clarke’s six-phased approach to Thematic Analysis. Four main themes were generated in relation to the experiences: (i) one-off blanket dietary advice (ii) education in a vacuum (iii) diabetes-hypertension diet dichotomy and (iv) imbalanced power relationship. The study underscores the need for a reconfiguration of diet-related health education in The Gambia to include lived experiences as critical components of health promotion in tackling T2DM and hypertension. This requires an ecological approach, critical health education, regulations on unhealthy foods, and active participation of individuals as equal partners in health education.
Isogenic pairs of induced-pluripotent stem-derived endothelial cells identify DYRK1A/PPARG/EGR1 pathway is responsible for Down syndrome-associated pulmonary hypertension
Authors: Suginobe Hidehiro , Ishida Hidekazu , Ishii Yoichiro , Ueda Kazutoshi , Yoshihara Chika , Ueyama Atsuko , Wang Renjie , Tsuru Hirofumi , Hashimoto Kazuhisa , Hirose Masaki , Ishii Ryo , Narita Jun , Kitabatake Yasuji , Ozono Keiichi
Published: October 2023

Down syndrome (DS) is the most prevalent chromosomal disorder associated with a higher incidence of pulmonary arterial hypertension (PAH). The dysfunction of vascular endothelial cells (ECs) is known to cause pulmonary arterial remodeling in PAH, although the physiological characteristics of ECs harboring trisomy 21 (T21) are still unknown. In this study, we analyzed the human vascular ECs by utilizing the isogenic pairs of T21-induced pluripotent stem cells (iPSCs) and corrected disomy 21 (cDi21)-iPSCs. In T21-iPSC-derived ECs, apoptosis and mitochondrial reactive oxygen species (mROS) were significantly increased, and angiogenesis and oxygen consumption rate (OCR) were significantly impaired as compared with cDi21-iPSC-derived ECs. The RNA-sequencing identified that EGR1 on chromosome 5 was significantly upregulated in T21-ECs. Both EGR1 suppression by siRNA and pharmacological inhibitor could recover the apoptosis, mROS, angiogenesis, and OCR in T21-ECs. Alternately, the study also revealed that DYRK1A was responsible to increase EGR1 expression via PPARG suppression, and that chemical inhibition of DYRK1A could restore the apoptosis, mROS, angiogenesis, and OCR in T21-ECs. Finally, we demonstrated that EGR1 was significantly upregulated in the pulmonary arterial ECs from lung specimens of a patient with DS and PAH. In conclusion, DYRK1A/PPARG/EGR1 pathway could play a central role for the pulmonary EC functions and thus be associated with the pathogenesis of PAH in DS.
Early Initiation of Antiretroviral Therapy Preserves the Metabolic Function of CD4+ T Cells in Subtype C Human Immunodeficiency Virus 1 Infection
Authors: Naidoo Kewreshini K , Highton Andrew J , Baiyegunhi Omolara O , Bhengu Sindiswa P , Dong Krista L , Bunders Madeleine J , Altfeld Marcus , Ndung’u Thumbi
Published: October 2023

Background

Immune dysfunction often persists in people living with human immunodeficiency virus (HIV) who are on antiretroviral therapy (ART), clinically manifesting as HIV-1-associated comorbid conditions. Early ART initiation may reduce incidence of HIV-1–associated immune dysfunction and comorbid conditions. Immunometabolism is a critical determinant of functional immunity. We investigated the effect of HIV-1 infection and timing of ART initiation on CD4+ T cell metabolism and function.

Methods

Longitudinal blood samples from people living with HIV who initiated ART during hyperacute HIV-1 infection (HHI; before peak viremia) or chronic HIV-1 infection (CHI) were assessed for the metabolic and immune functions of CD4+ T cells. Metabolite uptake and mitochondrial mass were measured using fluorescent analogues and MitoTracker Green accumulation, respectively, and were correlated with CD4+ T cell effector functions.

Results

Initiation of ART during HHI prevented dysregulation of glucose uptake by CD4+ T cells, but glucose uptake was reduced before and after ART initiation in CHI. Glucose uptake positively correlated with interleukin-2 and tumor necrosis factor-α production by CD4+ T cells. CHI was associated with elevated mitochondrial mass in effector memory CD4+ T cells that persisted after ART and correlated with PD-1 expression.

Conclusions

ART initiation in HHI largely prevented metabolic impairment of CD4+ T cells. ART initiation in CHI was associated with persistently dysregulated immunometabolism of CD4+ T cells, which was associated with impaired cellular functions and exhaustion.
Proline-rich transmembrane protein 2 knock-in mice present dopamine-dependent motor deficits
Authors: Hatta Daisuke , Kanamoto Kaito , Makiya Shiho , Watanabe Kaori , Kishino Tatsuya , Kinoshita Akira , Yoshiura Koh-Ichiro , Kurotaki Naohiro , Shirotani Keiro , Iwata Nobuhisa
Published: October 2023

Mutations of proline-rich transmembrane protein 2 (PRRT2) lead to dyskinetic disorders such as paroxysmal kinesigenic dyskinesia (PKD), which is characterized by attacks of involuntary movements precipitated by suddenly initiated motion, and some convulsive disorders. Although previous studies have shown that PKD might be caused by cerebellar dysfunction, PRRT2 has not been sufficiently analyzed in some motor-related regions, including the basal ganglia, where dopaminergic neurons are most abundant in the brain. Here, we generated several types of Prrt2 knock-in (KI) mice harboring mutations, such as c.672dupG, that mimics the human pathological mutation c.649dupC and investigated the contribution of Prrt2 to dopaminergic regulation. Regardless of differences in the frameshift sites, all truncating mutations abolished Prrt2 expression within the striatum and cerebral cortex, consistent with previous reports of similar Prrt2 mutant rodents, confirming the loss-of-function nature of these mutations. Importantly, administration of l-dopa, a precursor of dopamine, exacerbated rotarod performance, especially in Prrt2-KI mice. These findings suggest that dopaminergic dysfunction in the brain by the PRRT2 mutation might be implicated in a part of motor symptoms of PKD and related disorders.
A Review and Quality Assessment of TikTok Videos for Burn Education
Authors: Sheikh-Oleslami Sara , Tuen Young Ji , Courtemanche Rebecca , Hynes Sally
Published: October 2023

Social media platforms can serve as a readily accessible tool for burn education, potentially reducing the incidence and severity of burn injuries. Previous studies have investigated the quality of online burn education videos on platforms such as YouTube. Here, we review the quality of such videos on TikTok, a newer and rapidly growing platform. TikTok was searched for English videos using 29 keywords (hashtags) such as #burn, #education, #prevention, and #management. The first 30 videos per hashtag were screened. Videos were categorized by content and creator. Two independent reviewers assessed the quality of the included videos using the Global Quality Scale (GQS). Metrics such as views, commentary, and likes were also examined. Of 535 screened videos, 72 met inclusion criteria. 47% (n = 34) were on management, 33% (n = 31) education, and 10% (n = 7) prevention. Only 6% (n = 4) cited sources. The median GQS score was 3.0 (IQR: 2.0–3.0, max 4.0). 50% (n = 36) were made by healthcare professionals with a median GQS score of 3.0 (IQR: 2.0–3.0, max 4.0) compared to 2.0 (IQR: 2.0–3.0, max 4.0) in nonhealthcare professionals (n = 36). Viewership varied from 41 to 4.2 million views. Overall, there is a lack of high-quality educational information on TikTok. This rapidly expanding and dynamic platform may provide an opportunity to direct individuals to higher quality resources.
Introduction: Irregularized Humanitarian Migrants—Policies, Rationales, and the Search for More Durable Solutions
Authors: van Houte Marieke , Kaşlı Zeynep , Leerkes Arjen
Published: October 2023

In this special issue, we seek explanations for international- and local-level variations in policy approaches to ‘irregularized humanitarian migrants’, who left their country of citizenship in hopes of finding protection abroad but do not, or no longer, hold a permanent legal status. We shed light on different policy responses and experiences across Europe, Africa, and the wider Middle East by drawing on a wide array of political systems and migration patterns and different groups of humanitarian migrants. We explore to what extent the outcomes of various policies and practices can be regarded as better and more durable solutions, defined as increasingly taking into account the interests of migrants and the communities they live in. Ultimately, we stress the importance of gaining deeper and more comprehensive understandings of the historically informed context-specific circumstances that irregularized humanitarian migrants find themselves in, as well as the patterns that we see emerging in the comparison of these cases.
DNA mismatch repair protects the genome from oxygen-induced replicative mutagenesis
Authors: Lózsa Rita , Németh Eszter , Gervai Judit Z , Márkus Bence G , Kollarics Sándor , Gyüre Zsolt , Tóth Judit , Simon Ferenc , Szüts Dávid
Published: October 2023

DNA mismatch repair (MMR) corrects mismatched DNA bases arising from multiple sources including polymerase errors and base damage. By detecting spontaneous mutagenesis using whole genome sequencing of cultured MMR deficient human cell lines, we show that a primary role of MMR is the repair of oxygen-induced mismatches. We found an approximately twofold higher mutation rate in MSH6 deficient DLD-1 cells or MHL1 deficient HCT116 cells exposed to atmospheric conditions as opposed to mild hypoxia, which correlated with oxidant levels measured using electron paramagnetic resonance spectroscopy. The oxygen-induced mutations were dominated by T to C base substitutions and single T deletions found primarily on the lagging strand. A broad sequence context preference, dependence on replication timing and a lack of transcriptional strand bias further suggested that oxygen-induced mutations arise from polymerase errors rather than oxidative base damage. We defined separate low and high oxygen–specific MMR deficiency mutation signatures common to the two cell lines and showed that the effect of oxygen is observable in MMR deficient cancer genomes, where it best correlates with the contribution of mutation signature SBS21. Our results imply that MMR corrects oxygen-induced genomic mismatches introduced by a replicative process in proliferating cells.
CROST: a comprehensive repository of spatial transcriptomics
Authors: Wang Guoliang , Wu Song , Xiong Zhuang , Qu Hongzhu , Fang Xiangdong , Bao Yiming
Published: October 2023

The development of spatial transcriptome sequencing technology has revolutionized our comprehension of complex tissues and propelled life and health sciences into an era of spatial omics. However, the current availability of databases for accessing and analyzing spatial transcriptomic data is limited. In response, we have established CROST (https://ngdc.cncb.ac.cn/crost), a comprehensive repository of spatial transcriptomics. CROST encompasses high-quality samples and houses 182 spatial transcriptomic datasets from diverse species, organs, and diseases, comprising 1033 sub-datasets and 48 043 tumor-related spatially variable genes (SVGs). Additionally, it encompasses a standardized spatial transcriptome data processing pipeline, integrates single-cell RNA sequencing deconvolution spatial transcriptomics data, and evaluates correlation, colocalization, intercellular communication, and biological function annotation analyses. Moreover, CROST integrates the transcriptome, epigenome, and genome to explore tumor-associated SVGs and provides a comprehensive understanding of their roles in cancer progression and prognosis. Furthermore, CROST provides two online tools, single-sample gene set enrichment analysis and SpatialAP, for users to annotate and analyze the uploaded spatial transcriptomics data. The user-friendly interface of CROST facilitates browsing, searching, analyzing, visualizing, and downloading desired information. Collectively, CROST offers fresh and comprehensive insights into tissue structure and a foundation for understanding multiple biological mechanisms in diseases, particularly in tumor tissues.
A generalizable scaffold-based approach for structure determination of RNAs by cryo-EM
Authors: Langeberg Conner J , Kieft Jeffrey S
Published: October 2023

Single-particle cryo-electron microscopy (cryo-EM) can reveal the structures of large and often dynamic molecules, but smaller biomolecules (≤50 kDa) remain challenging targets due to their intrinsic low signal to noise ratio. Methods to help resolve small proteins have been applied but development of similar approaches to aid in structural determination of small, structured RNA elements have lagged. Here, we present a scaffold-based approach that we used to recover maps of sub-25 kDa RNA domains to 4.5–5.0 Å. While lacking the detail of true high-resolution maps, these maps are suitable for model building and preliminary structure determination. We demonstrate this method helped faithfully recover the structure of several RNA elements of known structure, and that it promises to be generalized to other RNAs without disturbing their native fold. This approach may streamline the sample preparation process and reduce the optimization required for data collection. This first-generation scaffold approach provides a robust system to aid in RNA structure determination by cryo-EM and lays the groundwork for further scaffold optimization to achieve higher resolution.
CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2016—2020
Authors: Ostrom Quinn T , Price Mackenzie , Neff Corey , Cioffi Gino , Waite Kristin A , Kruchko Carol , Barnholtz-Sloan Jill S
Published: October 2023

The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control and Prevention and the National Cancer Institute, is the largest population-based registry focused exclusively on primary brain and other central nervous system (CNS) tumors in the United States (US) and represents the entire US population. This report contains the most up-to-date population-based data on primary brain tumors available and supersedes all previous CBTRUS reports in terms of completeness and accuracy. All rates are age-adjusted using the 2000 US standard population and presented per 100,000 population. The average annual age-adjusted incidence rate (AAAIR) of all malignant and non-malignant brain and other CNS tumors was 24.83 per 100,000 population (malignant AAAIR=6.94 and non-malignant AAAIR=17.88). This overall rate was higher in females compared to males (27.85 versus 21.62 per 100,000) and non-Hispanic persons compared to Hispanic persons (25.24 versus 22.61 per 100,000). Gliomas accounted for 26.3% of all tumors. The most commonly occurring malignant brain and other CNS histopathology was glioblastoma (14.2% of all tumors and 50.9% of all malignant tumors), and the most common predominantly non-malignant histopathology was meningioma (40.8% of all tumors and 56.2% of all non-malignant tumors). Glioblastomas were more common in males, and meningiomas were more common in females. In children and adolescents (ages 0-19 years), the incidence rate of all primary brain and other CNS tumors was 6.13 per 100,000 population. There were 86,030 deaths attributed to malignant brain and other CNS tumors between 2016 and 2020. This represents an average annual mortality rate of 4.42 per 100,000 population and an average of 17,206 deaths per year. The five-year relative survival rate following diagnosis of a malignant brain and other CNS tumor was 35.7%, for a non-malignant brain and other CNS tumor the five-year relative survival rate was 91.8%.
Testing spatial working memory in pigs using an automated T-maze
Authors: Allen L M , Murphy D A , Roldan V , Moussa M N , Draper A , Delgado A , Aguiar M , Capote M A , Jarome T J J , Lee K , Mattfeld A T , Prather R , Allen T A
Published: October 2023

Pigs are an important large animal model for translational clinical research but underutilized in behavioral neuroscience. This is due, in part, to a lack of rigorous neurocognitive assessments for pigs. Here, we developed a new automated T-maze for pigs that takes advantage of their natural tendency to alternate. The T-maze has obvious cross-species value having served as a foundation for cognitive theories across species. The maze (17′ × 13′) was constructed typically and automated with flanking corridors, guillotine doors, cameras, and reward dispensers. We ran nine pigs in (1) a simple alternation task and (2) a delayed spatial alternation task. Our assessment focused on the delayed spatial alternation task which forced pigs to wait for random delays (5, 60, 120, and 240 s) and burdened spatial working memory. We also looked at self-paced trial latencies, error types, and coordinate-based video tracking. We found pigs naturally alternated but performance declined steeply across delays (R2 = 0.84). Self-paced delays had no effect on performance suggestive of an active interference model of working memory. Positional and head direction data could differentiate subsequent turns on short but not long delays. Performance levels were stable over weeks in diverse strains and sexes, and thus provide a benchmark for future neurocognitive assessments in pigs.
Trends of disease activity in Japanese patients over 75 years with rheumatoid arthritis from 2014 to 2021: the ANSWER cohort study
Authors: Yamada Hirotaka , Jinno Sadao , Maeda Toshihisa , Hayashi Shinya , Yamamoto Wataru , Onishi Akira , Onizawa Hideo , Takeuchi Tohru , Hiramatsu Yuri , Okita Yasutaka , Ebina Kosuke , Son Yonsu , Yoshida Naofumi , Watanabe Ryu , Hara Ryota , Yamashita Mai , Nose Yoko , Yamamoto Yuzuru , Okano Takaichi , Nishimura Keisuke , Ueda Yo , Sendo Sho , Hashimoto Motomu , Kuroda Ryosuke , Saegusa Jun
Published: October 2023

Objectives

To investigate if disease activity among elderly RA patients >75 years of age has changed over time in the real-world clinical setting.

Methods

Data from an observational multicentre registry of RA patients in Japan were analysed. The primary outcome was to evaluate the changes in the proportion of very elderly RA patients (>75 years) who achieved remission and low disease activity (LDA), from 2014 to 2021. The secondary outcome was to identify factors associated with remission and LDA by comparing demographic and clinical characteristics among the patients who had a study visit within the study period, using multivariate logistic regression.

Results

A total of 32 161 patient visits were identified from 2014 to 2021. The proportion of patients >75 years of age increased from 16.5% to 26.9%, with biologics and targeted synthetic DMARDs (b/tsDMARDs) use increasing and glucocorticoids use decreasing, while conventional synthetic DMARDs use remained relatively stable. The proportion of RA patients >75 years of age achieving remission and LDA significantly increased from 62.2% to 78.2% (P for trend < 0.001). A negative factor associated with achieving remission and LDA was glucocorticoid use, seropositivity and a history of previous b/tsDMARDs use while MTX use was associated positively, independent of other predictors.

Conclusions

In our cohort, disease activity among very elderly RA patients has improved over time. The study suggests the importance of using a treat-to-target approach in very elderly RA patients to improve clinical outcomes.
The potential role of upregulated PARP-1/RIPK1 expressions in amikacin-induced oxidative damage and nephrotoxicity in Wistar rats
Authors: El Latif Amera Abd , Zahra Abo Elnasr A , Badr AlShimaa , Elbialy Zizy I , Alghamdi Abdullah A A , Althobaiti Norah A , Assar Doaa H , Abouzed Tarek kamal
Published: October 2023

This study aimed to investigate the gene expression levels associated with nephrotoxic action of amikacin, as well as the post-treatment effect of diuretics on its nephrotoxic effects. Sixty male rats were divided equally into six groups, including the control group receiving saline intra-peritoneally (ip), and the five treated groups including therapeutic and double therapeutic dose groups, injected ip (15 and 30 mg/kg b.wt./day) respectively for seven days, and another two rat groups treated as therapeutic and double therapeutic dose groups then administered the diuretic orally for seven days and the last group received amikacin ip at a rate of 15 mg/kg/day for seven days, then given free access to water without diuretics for another seven days and was kept as a self-recovery group. Amikacin caused kidney injury, which was exacerbated by the double therapeutic dose, as evidenced by abnormal serum renal injury biomarkers, elevated renal MDA levels, inhibition of renal catalase and SOD enzyme activities, with renal degenerative and necrotic changes. Moreover, comet assays also revealed renal DNA damage. Interestingly, amikacin administration markedly elevated expression levels of the PARP-1, RIP1, TNF-α, IL-1β, and iNOS genes as compared to the control group. However, compared to the self-recovery group, post-amikacin diuretic treatment modulates amikacin-induced altered findings and alleviates amikacin nephrotoxic effects more efficiently. Our findings suggested the potential role of PARP-1 and RIPK1 expressions that influence the expression of proinflammatory cytokines such as IL-1β and TNF-α by exaggerating oxidative stress which may contribute to the pathogenesis of amikacin-induced nephrotoxicity.
Misophonia and Hearing Comorbidities in a Collegiate Population
Authors: Brennan Caroline R. , Lindberg Ragnar R. , Kim Gibbeum , Castro Ariana A. , Khan Rafay A. , Berenbaum Howard , Husain Fatima T.
Published: October 2023

Objectives:

Misophonia is a little-understood disorder in which certain sounds cause a strong emotional response in those who experience it. People who are affected by misophonia may find that noises like loud chewing, pen clicking, and/or sniffing trigger intense frustration, anger, or discomfort. The relationship of misophonia with other auditory disorders including loudness hyperacusis, tinnitus, and hearing loss is largely underexplored. This project aimed to investigate the prevalence and hearing-health comorbidities of misophonia in a college-aged population by using an online survey.

Design:

A total of 12,131 undergraduate and graduate students between the ages of 18 and 25 were given the opportunity to answer an in-depth online survey. These students were sampled in a roughly 50 of 50 sex distribution. The survey was created using Qualtrics and included the following components: electronic consent, demographics questionnaire, Misophonia Questionnaire (MQ), Khalfa’s Hyperacusis Questionnaire (HQ), Tinnitus and Hearing Survey, and Tinnitus Functional Index (TFI). To be eligible for compensation, answers for each of the above components were required, with the exception of the TFI, which was only presented to students who indicated that they experienced tinnitus. Respondents were determined to have high or possible likelihood of having misophonia if they gave specific answers to the MQ’s Emotion and Behavior Scale or the MQ Severity Scale.

Results:

After excluding duplicate responses and age-related outliers, 1,084 responses were included in the analysis. Just over 20% (n = 217) of the sample was determined to have a high or probable likelihood of having misophonia. The sample was primarily White, female, and of mid-to-high socioeconomic status. There was a strong positive correlation between MQ total scores and HQ total scores. High likelihood misophonia status showed a significant relationship with self-reported hearing loss and tinnitus. No statistically significant relationship was found between misophonia and age, ethnicity, or socioeconomic status. MQ total scores differed significantly when separating respondents by sex, self-reported tinnitus, and loudness hyperacusis. White respondents had significantly higher MQ total scores than Asian/Asian American respondents.

Conclusions:

The estimated prevalence of misophonia was about 8% to 20% of the sample, which agrees with most of the currently published research examining misophonia symptoms in collegiate populations. Results of data analysis suggest that misophonia severity may be related to loudness hyperacusis, sex, and possibly tinnitus. Future studies are needed to further examine the characteristics of these relationships, possibly in populations more optimized to reflect the general population or those with hearing-health disorders.
Increasing Incidence and Decreasing Mortality of Melanoma in Elderly Adults: An Epidemiologic Study in Olmsted County, Minnesota
Authors: Proffer Sydney L. , Reinhart Jacob P. , Campbell Elliott H. , Crum Olivia M. , Gibson Lawrence E. , Brewer Jerry D. , Demer Addison M.
Published: October 2023

BACKGROUND AND OBJECTIVE

Primary cutaneous melanoma incidence is increasing in elderly individuals. This population-based cohort examines incidence and mortality rates among adults aged 61 years and older with cutaneous melanoma.

MATERIALS AND METHODS

Using the Rochester Epidemiology Project, patients aged 61 years of age or older with a first lifetime diagnosis of cutaneous melanoma between January 1, 1970 and December 31, 2020 were identified.

RESULTS

The age- and sex-adjusted incidence rate increased from 16.4 (95% CI, 8.2–24.6) per 100,000 person-years in 1970 to 1979 to 201.5 (95% CI, 185.1–217.8) per 100,000 person-years in 2011 to 2020 (12.3-fold increase). There was a 16.0x increase in males and an 8.5× increase in females. Melanoma incidence has stabilized in males (1.2-fold increase, p = .11) and continues to significantly increase in females (2.7-fold increase, p < .001). Older age at diagnosis was significantly associated with an increased risk of death (HR 1.23 per 5-year increase in age at diagnosis, 95% CI, 1.02–1.47).

CONCLUSION

Melanoma incidence continues to increase since 1970. The incidence has risen in elderly females, but has stabilized in males. Mortality has decreased throughout this period.
Economic impact of urinary incontinence and pelvic organ prolapse in women in Belize
Authors: Zillioux Jacqueline , Yeaman Clinton , Desai Raj , Sharma Devang , Balkrishnan Rajesh , Rapp David
Published: October 2023

Introduction:

Urinary incontinence (UI) and pelvic organ prolapse (POP) are prevalent in low-income and middle-income countries (LMIC). Although the significant clinical and social impacts of UI/POP are well-described, less is known regarding their microeconomic impacts. This study aimed to assess the microeconomic impact of UI/POP in the LMIC country of Belize.

Methods:

The authors performed a prospective survey-based assessment of patients with urologic disease during surgical trips to Belize in 2019–2021 by the charity Global Surgical Expedition. This study is a post-hoc analysis focused on a subset with urogynecologic disorders. Patients completed a 17-item survey focused on disease impact on work, caretaker responsibilities, and finances. The primary study outcome was income loss resulting from work impairment or absence related to UI/POP, calculated using the validated work productivity and activity impairment questionnaire.

Results:

Forty-nine women with UI (n=15) and POP (n=34) completed surveys. The majority (73% UI; 88% POP) reported their condition negatively impacted their lives. In the analysis of 21 patients able to provide financial data, 6 (29%) patients reported missing work and 10 (48%) reported impairment at work due to UI/POP. This resulted in a loss of 6.7% (UI) and 8.5% (POP) in total income per capita. When also accounting for direct treatment costs, the total cost attributable to UI/POP was 28% (2%, 51%) of weekly income.

Conclusions:

In Belize, UI and POP significantly impair work and caretaking responsibilities, resulting in considerable lost income and cost. Efforts are thus necessary to provide surgical care for UI/POP in LMIC to address not only the quality of life but also the financial health of individuals and families.
The Inflammatory and Cytological Effect of Repeated Povidone-Iodine Application in Patients Receiving Intravitreal Injections
Authors: Akbulut Ersin , Kirik Furkan , Ekinci Aslanoglu Cansu , Hekimoglu Emine Rümeysa , Haciosmanoglu Aldogan Ebru , Ozdemir Mehmet Hakan
Published: October 2023

Objective:

To investigate the effect of repeated povidone-iodine (PVI) application on the ocular surface parameters of patients who received intravitreal injections.

Materials and methods:

In this prospective study, 52 eyes of 52 patients with age-related macular degeneration who underwent unilateral intravitreal injection at least three times in the last 1 year (intravitreal injection [IVI] group), 52 fellow eyes with no previous intravitreal injection (NIVI group), and 51 eyes of 51 healthy subjects (control) were included. Tear break-up time (TBUT), the Schirmer test, the Oxford staining score, the Ocular Surface Disease Index questionnaire, conjunctival impression cytology, and tear inflammatory cytokine levels (interleukin [IL]-1β and IL-6) were analyzed in all participants.

Results:

The IVI group had lower TBUT and higher Oxford staining score than the NIVI and control groups (P<0.05). No significant difference was found between the groups in the Schirmer test (P=0.161). Conjunctival impression cytology analysis revealed that the IVI group had a significantly lower goblet cell count and significantly higher Nelson staging result than the NIVI and control groups (P<0.05). As a result of tear cytokine analysis, although IVI and NIVI groups had higher IL-1β and IL-6 levels than the control group (P<0.05), there was no difference between NIVI and IVI groups (P≥0.05).

Conclusion:

Repeated PVI application caused cytotoxic injury to the ocular surface, resulting in goblet cell loss and squamous metaplasia of epithelial cells. As a result, the stability of the tear film layer was found to be impaired and ocular surface–related symptoms developed in patients.
Diagnostic accuracy of plasma brain natriuretic peptide for evaluation of dyspnea NYHA-III and NYHA-IV in emergency department of tertiary care hospital
Authors: Saghir Hina , Andaleeb Hina , Azhar Amina , Babu Sadia , Fatima Saadia , Mumtaz Hassan
Published: October 2023

Objective:

To determine the diagnostic accuracy of breathing not properly (BNP) for evaluation of dyspnea NYHA III and IV due to systolic heart failure in emergency department patients keeping echocardiography as the gold standard.

Study design:

Cross-sectional validation study. Setting: Department of Accident and Emergency Duration of Study: 25 July 2022–25 January 2023.

Subjects and methods:

A total of 115 of both sexes presenting with acute onset of dyspnea and having NYHA Class III and IV were included. Emergency nursing staff had immediately taken a single venous blood sample for BNP and creatinine levels and a 2D echo was performed. Ejection fraction was recorded, and the diagnosis of systolic heart failure on the basis of an ejection fraction, that is less than or equal to 45% was documented.

Results:

The age range in this study was from 18 to 65 years, with a mean age of 49.147±8.73 years. Mean BNP levels were 139.452±84.04 pg/ml. Patients with NYHA class III was 67.8 and 32.2% belongs to NYHA class IV. BNP levels greater than or equal to 100 pg/ml diagnosed 76 (66.1%) and echocardiography has diagnosed 68 (59.1%) patients with heart failure. BNP levels greater than or equal to 100 pg/ml had shown sensitivity 94.1%, specificity 74.5%, and diagnostic accuracy 86%, positive predictive value 84.21%, negative prediction value 89.74%, likelihood positive ratio 3.68 and likelihood negative ratio was 0.08 in diagnosis of heart failure.

Conclusion:

BNP estimation is a sensible and particular procedure for diagnosing CHF in patients who present to the emergency department with acute dyspnea and may add extra advantages to the administration of patients with congestive heart failure (CHF) in our population.
Eosinophil values in exacerbation and stable chronic obstructive pulmonary disease and its relationship to maintenance therapy in stable chronic obstructive pulmonary disease patients
Authors: Fachri Muhammad , Hatta Mochammad , Lestari Fira Indah , Akaputra Risky , Fatimah Fatimah , Wahab Athariq , Arliniy Yunita , Dwiyanti Ressy , Syukri Ahmad , Junita Ade Rifka , Febrianti Andini , Primaguna Muhammad Reza , Azhar Azhar
Published: October 2023

Background:

Chronic obstructive pulmonary disease (COPD) is characterised by persistent and progressive airflow limitations. The study aimed to determine the relationship between eosinophil values in patients with stable and exacerbated COPD, and the relationship of eosinophil values with two drug regimens used as maintenance therapy in stable COPD.

Materials and methods:

This cross-sectional study and the variables used in this study were eosinophil counts in stable and exacerbated COPD patients.

Results:

Eighty-three patients with stable and exacerbated COPD were included. Stable COPD (63.9%) was predominant, with the highest degree of symptoms in group A 18 patients (34%) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2; 35 patients (66%). The degree of COPD exacerbation was dominated by Type II COPD 15 patients (50%). Eosinophil counts in patients with stable COPD were less than 100 cells/mm3 37 patients (44.6%), while in patients with COPD exacerbation, it was greater than 100 cells/mm3 with a total of 30 patients (36.1%). Long acting muscarinic antagonist class of drugs was the most used treatment as maintenance therapy in stable COPD 34 patients (64.2%).

Conclusion:

The eosinophil counts in patients with COPD exacerbation were significantly higher than those in patients with stable COPD. The provision of maintenance therapy in the long acting β-2 agonist + inhaled glucocorticosteroid group of stable COPD patients was generally provided to COPD patients with eosinophil values greater than 100 cells/mm3, and the provision of long-term maintenance therapy in stable COPD patients was generally given to COPD patients with eosinophil values less than 100 cells/mm3.
Optimization of tissue microarray technique for breast cancer patients: a short communication
Authors: Harfouch Rim M. , Al-Shehabi Zuheir , Asaad Remal , Aljamali Majd , Issa Rana , Elshimali Yahya , Vadgama Jay
Published: October 2023

Background:

Tissue microarray (TMA) is a novel technique for studying different types of cancer tissues in one block. TMA is not yet established in Syria, so we aimed in this project to apply and set the most optimal conditions of TMA creation of breast cancer tissues at the Pathology Department of our institute.

Materials and Methods:

Eighty-eight blocks of breast cancer tissues were selected, considering the inclusion criteria. The tissue specimens of breast cancer patients were manually placed in the block by punching a core from a paraffin block, which was then released into a recipient block using a small trocar. Three different conditions were tested on the constructed TMA block.

Results:

We determined the most effective parameters that proved high quality: incubating the newly constructed block at a temperature of 43°C for 24 h in the oven and then cutting it the next day after cooling it to room temperature; also, cutting with a 5 μm thickness created the preferable stained slides later. CD3 staining showed high expression of tumor-infiltrating lymphocytes among triple-negative breast cancer patients and high expression of CD3 in triple-negative cancer patients.

Conclusion:

The optimization of parameters presented in our study resulted in perfect TMA generation and successful immunohistochemistry staining for cancer research at our institution.
A case report on enormous haemangioma of liver
Authors: Baral Pratik , Singh Bhandari Ramesh , Pradhan Sumita , Maharjan Narendra , Mainali Prakash , Regmi Dipesh , Kandel Krishna
Published: October 2023

Introduction:

Hemangiomas are the most common benign liver tumour. These tumours arise from the proliferation of vascular endothelial cells and increase in size owing to dilation. If their diameter exceeds 5 cm, they are classified as giant hemangiomas, while those surpassing 15 cm are considered enormous hemangiomas.

Case presentation:

A 38-year-old female patient presented with complaints of abdominal fullness for 18 months. Contrast-enhanced computed tomography was performed and two hemangiomas were diagnosed; the , larger one was an enormous hemangioma of size 20 × 16 cm. Non-anatomical hepatic resection was performed to remove the hemangiomas. The patient recovered well, without any complications.

Clinical discussion:

Hepatic hemangiomas are common, but hemangiomas greater than 15 cm in size are rare. They usually require no treatment unless the patient is symptomatic. Hepatectomy and enucleation of hemangioma are the most common surgical procedure for such hemangioma.

Conclusions:

Rarely, large hepatic hemangioma can be the cause of abdominal fullness lasting for months. Often, surgical intervention is required.
68Ga-FAPI PET/CT Imaging
Authors: Al-Ibraheem Akram , Abdlkadir Ahmed Saad , Alalawi Hasan , Badarneh Mohannad
Published: October 2023

68Ga-FAPI has been introduced recently in many nuclear medicine centers. Many pitfalls have been discussed previously. However, not all pitfalls are currently addressed in the literature. To our knowledge, this is the first reported case to address nonspecific 68Ga-FAPI expression at anorectal sphincter. A 69-year-old woman was diagnosed with intrahepatic cholangiocarcinoma. A 68Ga-FAPI scan was performed after diagnostic workup and chemoradiotherapy. In addition to 68Ga-FAPI–avid lesion at primary site, several nononcological ancillary findings have been observed. This includes unaddressed 68Ga-FAPI–avid focus within anorectal sphincter. Moreover, the same noteworthy findings were observed in the musculoskeletal and gynecological systems.
Screw Misposition and Detachment During Paranasal Augmentation: A Patient Report With Complication and Management
Authors: Yu Panxi , Lu Jianjian , Wang Tong
Published: October 2023

Paranasal concavity is esthetically displeasing and interferes with the overall outline of the face. Paranasal augmentation with alloplastic implants is a minimally invasive procedure with significant esthetic effects for paranasal concavity. When fixing the implants, the screws should be placed on the nasofrontal column, but are occasionally mispositioned on the anterior wall of the maxillary sinus. Here, the authors introduce a case of paranasal augmentation in which the self-tapping screw accidentally penetrated through the implant, broke through the anterior and medial walls of the maxillary sinus, and entered the nasal cavity. The screw was located by a computed tomography scan and was successfully removed under a nasal endoscope. The causes of this intraoperative complication were analyzed, emergent management was introduced, and a further preventive strategy was proposed.