bluuebunny/crossref_metadata_2025 huggingface dataset:
Toward multidimensional activity space-based segregation research
Authors: Ta Na
Published: April 2023

Measuring and explaining sociospatial segregation is essential in urban and social geography. Recent advances in activity space-based segregation provide new opportunities to study sociospatial segregation. This paper provides a comprehensive review of the emerging activity space-based segregation research in terms of measurements, dimensions, and influential factors. We highlight the trend toward integrating spatial, temporal, and social dimensions in activity space-based segregation measurement. Then, a multidimensional framework is constructed to cover the spatial form, opportunity exposure, spatiotemporal interaction, and social relationship of activity space-based segregation research. This paper ends with challenges and future directions for activity space-based segregation research, highlighting the importance of the temporal dimension, social interaction, influential mechanisms, and social effects.
Bionate® nucleus disc replacement: bench testing comparing two different designs
Authors: Vanaclocha Amparo , Vanaclocha Vicente , Atienza Carlos M. , Clavel Pablo , Jordá-Gómez Pablo , Barrios Carlos , Vanaclocha Leyre
Published: April 2023

Background

Intervertebral disc nucleus degeneration initiates a degenerative cascade and can induce chronic low back pain. Nucleus replacement aims to replace the nucleus while the annulus is still intact. Over time, several designs have been introduced, but the definitive solution continues to be elusive. Therefore, we aimed to create a new nucleus replacement that replicates intact intervertebral disc biomechanics, and thus has the potential for clinical applications.

Materials and methods

Two implants with an outer ring and one (D2) with an additional midline strut were compared. Static and fatigue tests were performed with an INSTRON 8874 following the American Society for Testing and Materials F2267-04, F2346-05, 2077-03, D2990-01, and WK4863. Implant stiffness was analyzed at 0–300 N, 500–2000 N, and 2000–6000 N and implant compression at 300 N, 1000 N, 2000 N, and 6000 N. Wear tests were performed following ISO 18192-1:2008 and 18192-2:2010. GNU Octave software was used to calculate movement angles and parameters. The statistical analysis package R was used with the Deducer user interface. Statistically significant differences between the two designs were analyzed with ANOVA, followed by a post hoc analysis.

Results

D1 had better behavior in unconfined compression tests, while D2 showed a “jump.” D2 deformed 1 mm more than D1. Sterilized implants were more rigid and deformed less. Both designs showed similar behavior under confined compression and when adding shear. A silicone annulus minimized differences between the designs. Wear under compression fatigue was negligible for D1 but permanent for D2. D1 suffered permanent height deformation but kept its width. D2 suffered less height loss than D1 but underwent a permanent width deformation. Both designs showed excellent responses to compression fatigue with no breaks, cracks, or delamination. At 10 million cycles, D2 showed 3-times higher wear than D1. D1 had better and more homogeneous behavior, and its wear was relatively low. It showed good mechanical endurance under dynamic loading conditions, with excellent response to axial compression fatigue loading without functional failure after long-term testing.

Conclusion

D1 performed better than D2. Further studies in cadaveric specimens, and eventually in a clinical setting, are recommended.

Level of evidence 2c.
A voting-based machine learning approach for classifying biological and clinical datasets
Authors: Daneshvar Negar Hossein-Nezhad , Masoudi-Sobhanzadeh Yosef , Omidi Yadollah
Published: April 2023

Background

Different machine learning techniques have been proposed to classify a wide range of biological/clinical data. Given the practicability of these approaches accordingly, various software packages have been also designed and developed. However, the existing methods suffer from several limitations such as overfitting on a specific dataset, ignoring the feature selection concept in the preprocessing step, and losing their performance on large-size datasets. To tackle the mentioned restrictions, in this study, we introduced a machine learning framework consisting of two main steps. First, our previously suggested optimization algorithm (Trader) was extended to select a near-optimal subset of features/genes. Second, a voting-based framework was proposed to classify the biological/clinical data with high accuracy. To evaluate the efficiency of the proposed method, it was applied to 13 biological/clinical datasets, and the outcomes were comprehensively compared with the prior methods.

Results

The results demonstrated that theTraderalgorithm could select a near-optimal subset of features with a significant level of p-value < 0.01 relative to the compared algorithms. Additionally, on the large-sie datasets, the proposed machine learning framework improved prior studies by ~ 10% in terms of the mean values associated with fivefold cross-validation of accuracy, precision, recall, specificity, and F-measure.

Conclusion

Based on the obtained results, it can be concluded that a proper configuration of efficient algorithms and methods can increase the prediction power of machine learning approaches and help researchers in designing practical diagnosis health care systems and offering effective treatment plans.
Adaptive evolution characteristics of mitochondrial genomes in genus Aparapotamon (Brachyura, Potamidae) of freshwater crabs
Authors: Ji Yu-Tong , Zhou Xiao-Juan , Yang Qian , Lu Yuan-Biao , Wang Jun , Zou Jie-Xin
Published: April 2023

Background

Aparapotamon, a freshwater crab genus endemic to China, includes 13 species. The distribution of Aparapotamon spans the first and second tiers of China's terrain ladder, showing great altitudinal differences. To study the molecular mechanisms of adaptive evolution in Aparapotamon, we performed evolutionary analyses, including morphological, geographical, and phylogenetic analyses and divergence time estimation. We sequenced the mitogenomes of Aparapotamon binchuanense and Aparapotamon huizeense for the first time and resequenced three other mitogenomes of Aparapotamon grahami and Aparapotamon gracilipedum. These sequences were combined with NCBI sequences to perform comparative mitogenome analysis of all 13 Aparapotamon species, revealing mitogenome arrangement and the characteristics of protein-coding and tRNA genes.

Results

A new species classification scheme of the genus Aparapotamon has been detected and verified by different aspects, including geographical, morphological, phylogenetics and comparative mitogenome analyses. Imprints from adaptive evolution were discovered in the mitochondrial genomes of group A, including the same codon loss at position 416 of the ND6 gene and the unique arrangement pattern of the tRNA-Ile gene. Multiple tRNA genes conserved or involved in adaptive evolution were detected. Two genes associated with altitudinal adaptation, ATP8 and ND6, which experienced positive selection, were identified for the first time in freshwater crabs.

Conclusions

Geological movements of the Qinghai-Tibet Plateau and Hengduan Mountains likely strongly impacted the speciation and differentiation of the four Aparapotamon groups. After some group A species dispersed from the Hengduan Mountain Range, new evolutionary characteristics emerged in their mitochondrial genomes, facilitating adaptation to the low-altitude environment of China's second terrain tier. Ultimately, group A species spread to high latitudes along the upper reaches of the Yangtze River, showing faster evolutionary rates, higher species diversity and the widest distribution.
High frequency of NDM-1 and OXA-48 carbapenemase genes among Klebsiella pneumoniae isolates in central Iran
Authors: Abbasi Elnaz , Ghaznavi-Rad Ehsanollah
Published: April 2023

Background

The emergence and distribution of multidrug-resistant (MDR) and carbapenem-resistant Klebsiella pneumoniae (CRKP) has become a global health threat. Therefore, this study aimed to investigate the frequency and antibiotic resistance patterns of MDR, extensively drug-resistant (XDR), and CRKP, as well as the antibiotic resistance genes of Klebsiella pneumoniae (K. pneumoniae) isolates from patients’ infectious samples from central Iran.

Methods

This study examined 546 clinical samples of patients to identify K. pneumoniae. The isolates were investigated for their antibiotic resistance profile, extended-spectrum β-lactamase (ESBL), AMPC β-lactamase, carbapenemase resistance, sulfonamide, tetracycline, plasmid-mediated quinolone resistance (PMQR) along with their resistance genes, integrase, and quaternary ammonium compounds (qac) by polymerase chain reaction (PCR).

Results

Out of 546 clinical samples, 121 (22.1%) cases of K. pneumoniae were identified using culture and PCR methods. The highest antibiotic resistance rates were found for ampicillin (119/121; 98.3%), cotrimoxazole (78/121; 64.4%), and cefixime, cefotaxime, ceftriaxone, and ceftazidime as a group (77/121; 63.6%). Tigecycline, colistin, and fosfomycin were the most effective antimicrobial agents with 98.4%, 96.7%, and 95.9% susceptibility, respectively. The amount of CRKP was 51 (42.1%). All CRKP isolates were MDR. The most abundant genes were blaTEM (77/77; 100%), blaCTX−M1 (76/77; 98.7%), blaSHV (76/77; 98.7%), blaCTX−M15 (73/77; 94.8%) for ESBL; blaCIT 28 (48.3%) and blaCMY−2 26 (44.8%) for AMPC β-lactamase; and blaOXA−48 46 (90.1%) and blaNDM 36 (70.5%) for carbapenemase. Among the PMQR determinants, qnrB (25/52; 48%), qnrS (19/52; 36.5%), and qnrA (11/52; 21.1%) were positive from the isolates. TetA and tetB were recognized in 25 (44.6%) and 17 (30.3%) isolates, respectively. Class 1 and 2 integrons were recognized in 97 (80.1%) and 53 (43.8%) isolates, respectively.

Conclusions

Due to the high prevalence of MDR and CRKP in central Iran, tracking and immediate intervention are necessary for control and inhibition of K. pneumoniae resistant isolates. Tigecycline, colistin, and fosfomycin are the best treatment options for treatment of patients with CRKP in this geographical area.
Zinc supplementation and light intensity affect 2-acetyl-1-pyrroline (2AP) formation in fragrant rice
Authors: Shuochen Jiang , Lihe Zhang , Fenqin Hu , Xiangru Tang , Bin Du
Published: April 2023

Background

Improving the yield and aroma content of fragrant rice is the focus of fragrant rice research. Light and Zinc (Zn) management generally cause regulations in the 2-acetyl-1-pyrroline (2AP) accumulation in fragrant rice. In addition, Zn promotes rice growth and improves rice yield, which has the potential to compensate for the negative impact of low light on fragrant rice yield. However, the potential of Zn to improve fragrant rice yield and 2AP content under shading conditions has not been verified.

Methods

Field experiments were conducted in the rice season (May–September) in 2019 to 2021. Two light i.e., normal light (NL) and low light (LL) and four Zn levels i.e., 0 kg Zn ha− 1 (N0), 1 kg Zn ha− 1 (Zn1), 2 kg Zn ha− 1(Zn2), and 3 kg Zn ha− 1 (Zn3), which applied at booting stage was set up. The grain yield, 2AP contents, Zn content in polished rice, photosynthesis related indicators, MDA content, antioxidant enzyme activity and the biochemical parameters related to 2AP formation were investigated.

Results

Shading reduced yield by 8.74% and increased 2AP content by 24.37%. In addition, shading reduced net photosynthetic rate (Pn), superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT), and increased proline, γ-aminobutyric acid (GABA), and pyrroline-5-carboxylic acid (P5C), proline dehydrogenase (PDH), △1-pyrroline-5-carboxylic acid synthetase (P5CS), malondialdehyde (MDA). With increasing Zn application levels, yield, 2AP, Zn content in polished rice, Pn, proline, P5C, GABA, PDH, P5CS, SOD, CAT and POD increased, and MDA decreased. Significant Light and Zn interaction effect on 2AP content was detected, and both shading and increasing Zn application increased the 2AP content.

Conclusion

Shading can increase the 2AP content but reduce the yield of fragrant rice. Increasing Zn application under shading conditions can further promote the biosynthesis of 2AP, but the effect of improving yield is limited.
A rare case report of the successful withdrawal of a stent balloon that failed to deflate
Authors: Yang Yong , Yang Shijun , Cheng Xiang , Liu Kun
Published: April 2023

Background

In current percutaneous coronary intervention (PCI) practice, the balloon used in the procedure should be deflated a short time after balloon dilation to avoid having prolonged balloon dilation in the coronary artery, which would block the coronary artery and cause myocardial ischemia. It is very rare for a dilated stent balloon to fail to deflate.

Case summary

A 44-year-old male was admitted to the hospital due to chest pain after exercise. Coronary angiography showed severe proximal stenosis of the right coronary artery (RCA) consistent with a diagnosis of coronary artery disease, and coronary stent implantation was required. After the last stent balloon was dilated, the stent balloon could not be deflated and continued to expand, resulting in blockage of the RCA blood flow. The patient then suffered decreased blood pressure and heart rate. Finally, the stent balloon in its expanded state was forcefully and directly withdrawn from the RCA and successfully removed from the body.

Conclusion

Deflation failure of a stent balloon is an extremely rare complication of PCI. Various treatment strategies can be considered based on hemodynamic status. In the case described herein, the balloon was pulled out of the RCA directly to restore blood flow, which kept the patient safe.
Comparing primary caregivers’ reported injury data with routinely recorded injury data to assess predictors of childhood injury
Authors: Ghebreab Luam , Kool Bridget , Lee Arier , Morton Susan
Published: April 2023

Background

Linking self-reported data collected from longitudinal studies with administrative health records is timely and cost-effective, provides the opportunity to augment information contained in each and can offset some of the limitations of both data sources. The aim of this study was to compare maternal-reported child injury data with administrative injury records and assess the level of agreement.

Methods

A deterministic linkage was undertaken to link injury-related data from the Growing up in New Zealand (GUiNZ) study to routinely collected injury records from New Zealand’s Accident Compensation Corporation (ACC) for preschool children. The analyses compared: (i) the characteristics of mothers with linked data vs. those without, (ii) injury incidences from maternal recall with those recorded in ACC injury claims, and (iii) the demographic characteristics of concordant and discordant injury reports, including the validity and reliability of injury records from both data sources.

Results

Of all mothers who responded to the injury questions in the GUiNZ study (n = 5836), more than 95% (n = 5637) agreed to have their child’s record linked to routine administrative health records. The overall discordance in injury reports showed an increasing trend as children grew older (9% at 9 M to 29% at 54 M). The mothers of children with discordance between maternal injury reports and ACC records were more likely to be younger, of Pacific ethnicity, with lower educational attainment, and live in areas of high deprivation (p < 0.001). The level of agreement between maternal injury recall and ACC injury record decreased (κ = 0.83 to κ = 0.42) as the cohort moved through their preschool years.

Conclusions

In general, the findings of this study identified that there was underreporting and discordance of the maternal injury recall, which varied by the demographic characteristics of mothers and their child’s age. Therefore, linking the routinely gathered injury data with maternal self-report child injury data has the potential to augment longitudinal birth cohort study data to investigate risk or protective factors associated with childhood injury.
Sample size calculations for indirect standardization
Authors: Wang Yifei , Chu Philip
Published: April 2023

Indirect standardization, and its associated parameter the standardized incidence ratio, is a commonly-used tool in hospital profiling for comparing the incidence of negative outcomes between an index hospital and a larger population of reference hospitals, while adjusting for confounding covariates. In statistical inference of the standardized incidence ratio, traditional methods often assume the covariate distribution of the index hospital to be known. This assumption severely compromises one’s ability to compute required sample sizes for high-powered indirect standardization, as in contexts where sample size calculation is desired, there are usually no means of knowing this distribution. This paper presents novel statistical methodology to perform sample size calculation for the standardized incidence ratio without knowing the covariate distribution of the index hospital and without collecting information from the index hospital to estimate this covariate distribution. We apply our methods to simulation studies and to real hospitals, to assess both its capabilities in a vacuum and in comparison to traditional assumptions of indirect standardization.
Simulating complex patient populations with hierarchical learning effects to support methods development for post-market surveillance
Authors: Davis Sharon E. , Ssemaganda Henry , Koola Jejo D. , Mao Jialin , Westerman Dax , Speroff Theodore , Govindarajulu Usha S. , Ramsay Craig R. , Sedrakyan Art , Ohno-Machado Lucila , Resnic Frederic S. , Matheny Michael E.
Published: April 2023

Background

Validating new algorithms, such as methods to disentangle intrinsic treatment risk from risk associated with experiential learning of novel treatments, often requires knowing the ground truth for data characteristics under investigation. Since the ground truth is inaccessible in real world data, simulation studies using synthetic datasets that mimic complex clinical environments are essential. We describe and evaluate a generalizable framework for injecting hierarchical learning effects within a robust data generation process that incorporates the magnitude of intrinsic risk and accounts for known critical elements in clinical data relationships.

Methods

We present a multi-step data generating process with customizable options and flexible modules to support a variety of simulation requirements. Synthetic patients with nonlinear and correlated features are assigned to provider and institution case series. The probability of treatment and outcome assignment are associated with patient features based on user definitions. Risk due to experiential learning by providers and/or institutions when novel treatments are introduced is injected at various speeds and magnitudes. To further reflect real-world complexity, users can request missing values and omitted variables. We illustrate an implementation of our method in a case study using MIMIC-III data for reference patient feature distributions.

Results

Realized data characteristics in the simulated data reflected specified values. Apparent deviations in treatment effects and feature distributions, though not statistically significant, were most common in small datasets (n < 3000) and attributable to random noise and variability in estimating realized values in small samples. When learning effects were specified, synthetic datasets exhibited changes in the probability of an adverse outcomes as cases accrued for the treatment group impacted by learning and stable probabilities as cases accrued for the treatment group not affected by learning.

Conclusions

Our framework extends clinical data simulation techniques beyond generation of patient features to incorporate hierarchical learning effects. This enables the complex simulation studies required to develop and rigorously test algorithms developed to disentangle treatment safety signals from the effects of experiential learning. By supporting such efforts, this work can help identify training opportunities, avoid unwarranted restriction of access to medical advances, and hasten treatment improvements.
Piloting an automated clinical trial eligibility surveillance and provider alert system based on artificial intelligence and standard data models
Authors: Meystre Stéphane M. , Heider Paul M. , Cates Andrew , Bastian Grace , Pittman Tara , Gentilin Stephanie , Kelechi Teresa J.
Published: April 2023

Background

To advance new therapies into clinical care, clinical trials must recruit enough participants. Yet, many trials fail to do so, leading to delays, early trial termination, and wasted resources. Under-enrolling trials make it impossible to draw conclusions about the efficacy of new therapies. An oft-cited reason for insufficient enrollment is lack of study team and provider awareness about patient eligibility. Automating clinical trial eligibility surveillance and study team and provider notification could offer a solution.

Methods

To address this need for an automated solution, we conducted an observational pilot study of our TAES (TriAl Eligibility Surveillance) system. We tested the hypothesis that an automated system based on natural language processing and machine learning algorithms could detect patients eligible for specific clinical trials by linking the information extracted from trial descriptions to the corresponding clinical information in the electronic health record (EHR). To evaluate the TAES information extraction and matching prototype (i.e., TAES prototype), we selected five open cardiovascular and cancer trials at the Medical University of South Carolina and created a new reference standard of 21,974 clinical text notes from a random selection of 400 patients (including at least 100 enrolled in the selected trials), with a small subset of 20 notes annotated in detail. We also developed a simple web interface for a new database that stores all trial eligibility criteria, corresponding clinical information, and trial-patient match characteristics using the Observational Medical Outcomes Partnership (OMOP) common data model. Finally, we investigated options for integrating an automated clinical trial eligibility system into the EHR and for notifying health care providers promptly of potential patient eligibility without interrupting their clinical workflow.

Results

Although the rapidly implemented TAES prototype achieved only moderate accuracy (recall up to 0.778; precision up to 1.000), it enabled us to assess options for integrating an automated system successfully into the clinical workflow at a healthcare system.

Conclusions

Once optimized, the TAES system could exponentially enhance identification of patients potentially eligible for clinical trials, while simultaneously decreasing the burden on research teams of manual EHR review. Through timely notifications, it could also raise physician awareness of patient eligibility for clinical trials.
Development and validation of a video-assisted liver biopsy technique using a minimally-invasive device
Authors: Almeida Alexandra Mano , Rocha Hermano Alexandre Lima , Araújo David Augusto Batista Sá , de Barros Silva Paulo Goberlânio , de Melo Filho Luís Pires , de Oliveira Borges Gleydson César
Published: April 2023

Background

Percutaneous liver biopsy is the gold standard technique for establishing the cause of cirrhosis and liver disease activity assessment. However, some cases of steatohepatitis or other chronic liver diseases show a high number of false negative results in samples obtained via the percutaneous route. This fact justifies performing a liver biopsy via the laparoscopic route. However, this is an expensive technique, with morbidities associated with pneumoperitoneum and anesthetic complications. The main objective of this study is to develop a video-assisted technique that uses only a minimally-invasive device for the liver biopsy and the optical trocar. Without additional trocars, this technique constitutes a less invasive procedure than the existing techniques in clinical practice.

Methods

This is a device development and validation study and patients submitted to abdominal laparoscopic surgery and required liver biopsy for moderate to severe steatosis were recruited. The patients were randomized into two groups: laparoscopic liver biopsy technique (n = 10, control group) and mini-laparoscopic liver biopsy technique (n = 8, experimental group). The times associated with procedure performance in both groups were evaluated using the Mann–Whitney or Kruskal–Wallis tests according to data distribution.

Results

At baseline, there was no statistical difference regarding gender and type of surgery. The experimental group had a significantly shorter time compared with the group that underwent the traditional procedure in mean procedure time (p = 0.003), biopsy time (p = 0.002) and hemostasis time (p = 0.003).

Conclusions

The mini-laparoscopic biopsy device and technique showed to be capable of safely obtaining sufficient tissue samples, which was minimally invasive and in a shorter time than the classic technique.
The care cascade for hepatitis C virus and prognosis of chronic hepatitis C patients treated with antiviral agents in a tertiary hospital
Authors: Yoo Sung Hwan , Kim Myung , Kim Sora , Lee Jung Il , Lee Kwan Sik , Lee Hyun Woong , Lim Jin Hong
Published: April 2023

Background

Some studies have analyzed the frequency of HCV RNA testing and actual treatment among anti-HCV positive patients in Korea, which has a low prevalence of HCV infection. This study aimed to analyze the diagnosis process, treatment results, and prognosis according to care cascade in patients who are anti-HCV positive.

Methods

Three thousand two hundred fifty-three anti-HCV positive patients presented to a tertiary hospital between January 2005 and December 2020. The number of patients who underwent HCV RNA testing, treatment, and proportion of sustained virologic response (SVR) according to the type of antivirals was investigated. We investigated the cumulative incidence of hepatocellular carcinoma (HCC) and liver cirrhosis.

Results

Of a total of 3,253 people, 1,177 (36.2%) underwent HCV RNA testing and 858 (72.9%) were positive for HCV RNA. 494 (57.6%) of HCV RNA positive patients received antiviral treatment, and 443 (89.7%) of initiated hepatitis C treatment experienced SVR. Of the 421 treated patients, 16 (14.2%) developed HCC. The cumulative incidence of HCC at 15 years was significantly different according to the presence of liver cirrhosis (10/83, 29.5% vs. 6/338, 10.8%, p < 0.001). The cumulative incidences of HCC or liver cirrhosis did not show significant differences according to the presence of SVR12 (14/388, 13.2% vs. 2/33, 52.5%, p = 0.084, 21/319, 15.0%, vs. 3/22, 28.7%, p = 0.051).

Conclusions

Owing to the introduction of direct-acting antivirals, high SVR12 was achieved, but the proportion of anti-HCV positive patients who received HCV RNA testing and treatment was not high. HCC surveillance after SVR12 is recommended for chronic hepatitis C patients with cirrhosis.
Mortality in COVID-19 older patients hospitalized in a geriatric ward: Is obesity protective?
Authors: Lagrandeur Julien , Putallaz Pauline , Krief Hélène , Büla Christophe J. , Coutaz Martial
Published: April 2023

Backgrounds

To investigate the relationship between obesity and 30-day mortality in a cohort of older hospitalized COVID-19 inpatients.

Methods

Included patients were aged 70 years or more; hospitalized in acute geriatric wards between March and December 2020; with a positive PCR for COVID-19; not candidate to intensive care unit admission. Clinical data were collected from patients electronic medical records. Data on 30-day mortality were retrieved from the hospital administrative database.

Results

Patients included (N = 294) were on average 83.4 ± 6.7 years old, 50.7% were women, and 21.7% were obese (BMI > 30 kg/m2). At 30-day, 85 (28.9%) patients were deceased. Compared to survivors in bivariable analysis, deceased patients were older (84.6 ± 7.6 vs 83.0 ± 6.3 years), more frequently with very complex health status (63.5% vs 39.7%, P < .001), but less frequently obese (13.4% vs 24.9%, P = .033) at admission. Over their stay, deceased patients more frequently (all P < .001) developed radiologic signs of COVID-19 (84.7% vs 58.9%), anorexia (84.7% vs 59.8%), hypernatremia (40.0% vs 10.5%), delirium (74.1% vs 30.1%), and need for oxygen (87.1% vs 46.4%) compared to survivors.

In multivariable analysis that controlled for all markers of poor prognosis identified in bivariable analysis, obese patients remain with 64% (adjOR 0.36, 95%CI 0.14–0.95, P = .038) lower odds to be deceased at 30-day than non-obese patients.

Conclusions

In this population of older COVID-19 inpatients, an inverse association between obesity and 30-day mortality was observed even after adjusting for all already-known markers of poor prognosis. This result challenges previous observations in younger cohorts and would need to be replicated.
Effectiveness of computer-based interventions for community-dwelling people with cognitive decline: a systematic review with meta-analyses
Authors: Zuschnegg Julia , Schoberer Daniela , Häussl Alfred , Herzog Sereina A. , Russegger Silvia , Ploder Karin , Fellner Maria , Hofmarcher-Holzhacker Maria M. , Roller-Wirnsberger Regina , Paletta Lucas , Koini Marisa , Schüssler Sandra
Published: April 2023

Background

Cognitive deficits arise with age and can increase the risk for subjective cognitive decline (SCD) and mild cognitive impairment (MCI), which may result in dementia, leading to health problems, care dependency and institutionalization. Computer-based cognitive interventions (CCIs) have the potential to act as important counteraction functions in preserving or improving cognition concomitant to available pharmacological treatment. The aim was to assess the effectiveness of CCIs performed individually with a personal or tablet computer, game console, virtual, augmented, or mixed reality application on cognition in community-dwelling people with SCD, MCI and dementia.

Methods

A systematic review with meta-analyses of randomized controlled trials (RCTs) was performed. The systematic literature search was conducted in MEDLINE, CINAHL, Embase, Cochrane CENTRAL, IEEE Xplore Digital Library, Web of Science, Scopus and PsycINFO. In addition, a search for gray literature and backward citation searching were carried out. To judge on the evidence, two reviewers independently used the Cochrane Risk of Bias Tool. The standardized mean difference (SDM) for pooling comparable studies using the random-effects model was applied.

Results

Twenty-four RCTs were identified, of which 1 RCT examined CCIs in individuals with SCD, 18 RCTs with MCI, and 6 RCTs with dementia. Most interventions were conducted with personal computers. Meta-analyses with 12 RCTs showed significant effects of computer-based cognitive interventions for people with MCI in the domains memory, working memory, attention/concentration/processing speed and executive functioning, but no significant improvements in global cognition and language. Regarding dementia a meta-analysis pooled with 4 RCTs demonstrated a tendency towards, but no significant increase of memory functions (SMD 0.33, CI 95% [-0.10, 0.77]). One RCT regarding SCD reported significant improvements in memory functions for participants conducting a cognitive training on a personal computer.

Conclusions

The results demonstrated that CCIs have beneficial effects on domain-specific cognition in people with MCI but no significant effects on people with dementia. In terms of SCD, one study showed significant improvements in memory functions. It seems that the beneficial effect for cognitive preservation or improvement due to CCIs occurs at the earliest intervention state. However, more research on SCD is needed.

Trial registration

PROSPERO International Prospective Register of Systematic Reviews CDR42020184069.
Sex and gender differences in treatment intention, quality of life and performance status in the first 100 patients with periampullary cancer enrolled in the CHAMP study
Authors: Olsson Hau Sofie , Williamsson Caroline , Andersson Bodil , Eberhard Jakob , Jirström Karin
Published: April 2023

Background

Periampullary cancer is a term for cancers arising in or in close proximity to the pancreas. Pancreatic cancer is the 3rd leading cause of cancer death for both sexes and while surgery is the only option for cure, chemotherapy is given in both the adjuvant and palliative settings. The aim of this study was to investigate any sex and gender differences in patients with pancreatic and other periampullary adenocarcinomas enrolled in a prospective, observational trial.

Methods

The study cohort consists of the first 100 patients, 49 women and 51 men, enrolled in the Chemotherapy, Host Response and Molecular dynamics in Periampullary cancer (CHAMP) study, an ongoing study of patients undergoing neoadjuvant, adjuvant or first-line palliative chemotherapy treatment. Twenty-five patients had surgery with curative intent and subsequent adjuvant treatment, and 75 patients were treated with palliative chemotherapy. Data regarding health-related quality of life (HRQoL, EORTC-QLQ-C30) at baseline, demographic and clinicopathological factors were examined and stratification by treatment intention according to sex. Overall survival (OS) was calculated through Kaplan–Meier analysis.

Results

There was a statistically significant difference between male and female patients treated with curative intent, with fewer women having undergone surgery (18 vs 7, p = 0.017), also after adjustment for age, tumor location and performance status. No statistical differences were found between the sexes regarding age, comorbidities, or clinicopathological factors. Before start of chemotherapy treatment, health-related quality of life (HRQoL) was lower in female than in male patients. However, HRQoL was not associated with performance status in female patients, whereas in male patients several HRQoL indicators were significantly positively associated with poorer performance status at baseline.

Conclusions

This study shows no clear differences between the sexes regarding biological factors concluding that gender bias might be responsible for the discrepancy between men and women being offered curative surgery. The observed difference between women and men regarding the association between HRQoL and performance status is unprecedented. Altogether these findings underline the importance of taking gender into consideration when assessing eligibility for curative surgery in order to improve biological outcome and decrease suffering in both sexes.

Trial registration

NCT03724994.
Utility of AMACR immunohistochemical staining in differentiating Arias-Stella reaction from clear cell carcinoma of ovary and endometrium
Authors: Nili Fatemeh , Sadri Masoumeh , Ameli Fereshteh
Published: April 2023

Background

The Arias-Stella reaction is a hormone-related atypical endometrial change characterized by cytomegaly, nuclear enlargement, and hyperchromasia of endometrial glands; typically associated with intrauterine or extrauterine pregnancies or with gestational trophoblastic disease. Although differentiating the Arias-Stella reaction (ASR) from clear cell carcinoma (CCC) of the endometrium is usually straightforward, but differentiating ASR might be difficult if it occurs outside the setting of pregnancy, in extra-uterine sites or in older patients. The aim of this study was to determine whether P504S/Alpha Methyacyl CoA racemase (AMACR) immunohistochemical (IHC) staining can be used to differentiate ASR from CCC.

Methods

Fifty endometrial ASR and 57 CCC samples were assessed by IHC staining with antibody for AMACR. The immunoreactive score (IRS) was based on total intensity score (no staining to strong scored as 0–3) + percentage score (0-100% categorized as 0–3) ranged from 0 to 6. Positive expression was considered as a total IRS exceeding 2.

Results

The mean age of the patients in the ASR was significantly lower than that of CCC (33.34 ± 6.36 and 57.81 ± 11.64 years old, respectively, p < 0.001). The overall AMACR staining score was significantly higher among CCC compared to ASR groups (p = 0.003). The positive and negative predictive values for AMACR expression in detecting CCC from ASR were 81.1% and 57%, respectively.

Conclusion

IHC staining for AMACR can be helpful and a member of discriminatory IHC panel when clinical or histologic features cannot facilitate the differential diagnosis between ASR versus CCC.
Intrathecal chemotherapy combined with systemic therapy in patients with refractory leptomeningeal metastasis of non-small cell lung cancer: a retrospective study
Authors: Zhou Tao , Zhu Shaofeng , Xiong Qiang , Gan Jiongli , Wei Jianping , Cai Jing , Liu Anwen
Published: April 2023

Background

Leptomeningeal metastasis (LM) is the most devastating complication of non-small cell lung cancer (NSCLC), and its incidence is increasing. There is currently no standard treatment for LM, and the efficacy of traditional intravenous drug treatment is low, making refractory LM a difficult problem. In this study, we evaluated the efficacy and safety of intrathecal chemotherapy (IC)-based regimens in patients with refractory LM.

Methods

We retrospectively enrolled NSCLC patients with confirmed LM who received IC and systemic therapy at the Second Affiliated Hospital of Nanchang University from December 2017 to July 2022. We analysed overall survival (OS), intracranial progression-free survival (iPFS), clinical response, and safety in these patients.

Results

A total of 41 patients were enrolled. The median number of IC treatments was seven (range: 2–22). Seven patients received intrathecal methotrexate, and 34 patients received intrathecal pemetrexed. Clinical manifestations related to LM improved after IC and systemic therapy in 28 (68.3%) patients. The median iPFS in the whole cohort was 8 months (95% confidence interval [CI]: 6.4–9.7 months), and the median OS was 10.1 months (95% CI: 6.8–13.4 months). Multivariate analysis of the 41 patients with LM using a Cox proportional risk model showed that bevacizumab was an independent prognostic factor in patients treated with combination therapy (p = 0.002; hazard ratio [HR] 0.240; 95% CI: 0.097–0.595). Poor ECOG performance status remained a significant predictor of poor prognosis for survival (p = 0.048; HR 2.560; 95% CI: 1.010–6.484). Myelosuppression was the major adverse event over all IC dose levels. There were 18 cases of myelosuppression, 15 cases of leukopenia, and nine cases of thrombocytopenia. Eleven patients had myelosuppression above grade 3, including four with thrombocytopenia and seven with leukopenia.

Conclusions

Combination therapy based on IC had good curative effects, was safe to use, and was associated with prolonged survival in NSCLC patients with LM. The use of bevacizumab is a good prognostic factor for NSCLC LM patients with combination therapy.
SLC27A2 mediates FAO in colorectal cancer through nongenic crosstalk regulation of the PPARs pathway
Authors: Shang Kun , Ma Nina , Che Juanjuan , Li Huihui , Hu Jiexuan , Sun Haolin , Cao Bangwei
Published: April 2023

Background

Peroxisome proliferator activated receptors (PPARs) are a nuclear hormone receptors superfamily that is closely related to fatty acid (FA) metabolism and tumor progression. Solute carrier family 27 member 2 (SLC27A2) is important for FA transportation and metabolism and is related to cancer progression. This study aims to explore the mechanisms of how PPARs and SLC27A2 regulate FA metabolism in colorectal cancer (CRC) and find new strategies for CRC treatment.

Methods

Biological information analysis was applied to detect the expression and the correlation of PPARs and SLC27A2 in CRC. The protein–protein interaction (PPI) interaction networks were explored by using the STRING database. Uptake experiments and immunofluorescence staining were used to analyse the function and number of peroxisomes and colocalization of FA with peroxisomes, respectively. Western blotting and qRT‒PCR were performed to explore the mechanisms.

Results

SLC27A2 was overexpressed in CRC. PPARs had different expression levels, and PPARG was significantly highly expressed in CRC. SLC27A2 was correlated with PPARs in CRC. Both SLC27A2 and PPARs were closely related to fatty acid oxidation (FAO)‒related genes. SLC27A2 affected the activity of ATP Binding Cassette Subfamily D Member 3 (ABCD3), also named PMP70, the most abundant peroxisomal membrane protein. We found that the ratios of p-Erk/Erk and p-GSK3β/GSK3β were elevated through nongenic crosstalk regulation of the PPARs pathway.

Conclusions

SLC27A2 mediates FA uptake and beta-oxidation through nongenic crosstalk regulation of the PPARs pathway in CRC. Targeting SLC27A2/FATP2 or PPARs may provide new insights for antitumour strategies.
Efficacy and safety of laser peripheral iridoplasty with different energy levels and locations in the treatment of primary angle closure disease assessed by swept-source anterior segment optical coherence tomography
Authors: Qin Jiayin , Zhang Yan , Zhang Chengxia , Niu Yaqian , Yang Fei , Wang Xijuan , Li Xiaochun , Yu Yang
Published: April 2023

Background

To explore the efficacy and safety of laser peripheral iridoplasty (LPIp) with different energy levels and locations in the treatment of primary angle closure disease (PACD) assessed by swept-source anterior segment optical coherence tomography (AS-OCT).

Methods

We enrolled patients with PACD following best-corrected visual acuity (BCVA), intraocular pressure (IOP), anterior chamber gonioscopy, ultrasound biomicroscopy(UBM), optic disc OCT, and visual field examinations. After Pentacam and AS-OCT measurements, the patients were randomly divided into four treatment groups for LPIp with two different energy levels (high vs. low energy) and two locations (far from the periphery vs. near the periphery) and combined with laser peripheral iridotomy. BCVA, IOP, pupil diameter, central anterior chamber depth, anterior chamber volume, anterior opening distance (AOD)500, AOD750, trabecular iris angle (TIA)500, and TIA750 in four quadrants before and after laser treatment were compared.

Results

We followed up 32 patients (64 eyes; average age, 61.80 ± 9.79 years; 8 patients/16 eyes per group) for up to 2 years. The IOP of all enrolled patients was decreased after surgery compared to that before (t = 3.297, P = 0.002), the volume of the anterior chamber was increased (t=-2.047, P = 0.047), and AOD500, AOD750, TIA500, and TIA750 were increased (all P < 0.05). Within-group comparisons showed that BCVA in the low-energy/far-periphery group was improved after surgery (P < 0.05). After surgery, the IOP was decreased in the two high-energy groups, whereas the volume of the anterior chamber, AOD500, AOD750, TIA500, and TIA750 were increased in all groups (all P < 0.05). However, when comparing every two groups, the high-energy/far-periphery group showed a stronger effect on pupil dilation than the low-energy/near-periphery group (P = 0.045). The anterior chamber volume in the high-energy/near-periphery group was larger than that in the high-energy/far-periphery group (P = 0.038). The change in TIA500 was for 6 points smaller in the low-energy/near-periphery group than in the low-energy/far-periphery group (P = 0.038). Other parameters showed no significant group differences.

Conclusion

LPIp combined with iridotomy can effectively reduce IOP, increase anterior chamber volume, increase chamber angle opening distance, and widen the trabecular iris angle. Intraoperatively, high-energy laser spots positioned one spot diameter from the scleral spur can obtain the best effect and safety. Swept-source AS-OCT can safely and effectively quantify the anterior chamber angle.
Autosomal recessive bestrophinopathy combined with neurofibromatosis type 1 in a patient
Authors: Zhao Bo , Chen Lian , Zhang Peng , He Ke , Lei Min , Zhang Juan
Published: April 2023

Background

Neurofibromatosis type 1 (NF1) is a multisystem genetic disorder that may affect multiple systems of the body. Autosomal recessive bestrophinopathy (ARB) is a rare retinal dystrophy caused by autosomal recessively mutations in bestrophin 1 (BEST1) gene. So far, we have not retrieved any case report of the same patient with both NF1 and BEST1 gene mutations.

Case presentation

An 8-year-old female patient with café-au-lait spots, freckling on skin presented to our ophthalmology clinic for routine ophthalmological examination. Her best corrected visual acuity (BCVA) was 20/20 in both eyes. Slit-lamp examination of both eyes revealed few yellowish-brown dome-shaped Lisch nodules over the iris surface. Fundus examination was notable for bilateral confluent yellowish subretinal deposits at macula, few yellow flecks at temporal retina, and cup-to-disc ratio of 0.2. Optical coherence tomography (OCT) revealed subretinal fluid (SRF) involving the fovea, elongated photoreceptor outer segments and mild intraretinal fluid (IRF) at bilateral macula. Fundus autofluorescence demonstrated hyperautofluorescence in the area corresponding to the subretinal deposits. Whole-exome sequencing and Sanger sequencing were used to investigate genetic mutation in the patient and her parents. A BEST1 gene heterozygous missense c.604 C > T (p.Arg202Trp) was identified in the patient and her mother. Also, the patient carries an NF1 nonsense mutation c.6637 C > T (p.Gln2213*) with the mosaic generalized phenotype. There were no visual impairments or obvious neurological, musculoskeletal, behavioral or other symptoms in this patient, so she was managed conservatively and advised to follow up regularly for a long time.

Conclusions

ARB and NF1, which are caused by two different pathogenic gene mutations, have rarely coexisted in the same patient. The discovery of pathogenic gene mutations may play a crucial role in more accurate diagnostics and genetic consultations for individuals and their families.