bluuebunny/crossref_metadata_2025 huggingface dataset:
Hemojuvelin-mediated hepcidin induction requires both bone morphogenetic protein type I receptors ALK2 and ALK3
Authors: Dogan Deniz Y. , Urzica Eugen I. , Hornung Isabelle , Kastl Philipp , Oguama David , Fette Franca M. , Nguyen Lien H. , Rosenbauer Frank , Zacharowski Kai , Klingmüller Ursula , Gradhand Elise , von Knethen Andreas , Popp Rüdiger , Fleming Ingrid , Schrader Lisa , Steinbicker Andrea U.
Published: April 2024

Hemojuvelin (HJV) is a glycosylphosphatidylinositol-anchored protein of the repulsive guidance molecule family acting as a bone morphogenetic protein (BMP) coreceptor to induce the hepatic iron regulatory protein hepcidin. Hepcidin causes ubiquitination and degradation of the sole known iron exporter ferroportin, thereby limiting iron availability. The detailed signaling mechanism of HJV in vivo has yet to be investigated. In the current manuscript, we used an established model of adeno-associated virus (AAV)-mediated liver-specific overexpression of HJV in murine models of hepatocyte-specific deficiency of the BMP type I receptors Alk2 or Alk3. In control mice, HJV overexpression increased hepatic Hamp messenger RNA (mRNA) levels, soluble HJV (sHJV), splenic iron content (SIC), as well as phosphorylated small mothers against decapentaplegic protein (pSMAD1/5/8) levels. In contrast, in Alk2fl/fl;Alb-Cre and Alk3fl/fl;Alb-Cre mice, which present with moderate and severe iron overload, respectively, the administration of AAV-HJV induced HJV and sHJV. However, it did not rescue the iron overload phenotypes of those mice. Serum iron levels were induced in Alk2fl/fl;Alb-Cre mice after HJV overexpression. In phosphate-buffered saline–injected Alk3fl/fl;Alb-Cre mice, serum iron levels and the expression of duodenal ferroportin remained high, whereas Hamp mRNA levels were decreased to 1% to 5% of the levels detected in controls. This was reduced even further by AAV-HJV overexpression. SIC remained low in mice with hepatocyte-specific Alk2 or Alk3 deficiency, reflecting disturbed iron homeostasis with high serum iron levels and transferrin saturation and an inability to induce hepcidin by HJV overexpression. The data indicate that ALK2 and ALK3 are both required in vivo for the HJV-mediated induction of hepcidin.
Proteomic profiling for biomarker discovery in heparin-induced thrombocytopenia
Authors: Nilius Henning , Hamzeh-Cognasse Hind , Hastings Janna , Studt Jan-Dirk , Tsakiris Dimitrios A. , Greinacher Andreas , Mendez Adriana , Schmidt Adrian , Wuillemin Walter A. , Gerber Bernhard , Vishnu Prakash , Graf Lukas , Kremer Hovinga Johanna A. , Bakchoul Tamam , Cognasse Fabrice , Nagler Michael
Published: April 2024

New analytical techniques can assess hundreds of proteins simultaneously with high sensitivity, facilitating the observation of their complex interplay and role in disease mechanisms. We hypothesized that proteomic profiling targeting proteins involved in thrombus formation, inflammation, and the immune response would identify potentially new biomarkers for heparin-induced thrombocytopenia (HIT). Four existing panels of the Olink proximity extension assay covering 356 proteins involved in thrombus formation, inflammation, and immune response were applied to randomly selected patients with suspected HIT (confirmed HIT, n = 32; HIT ruled out, n = 38; and positive heparin/platelet factor 4 [H/PF4] antibodies, n = 28). The relative difference in protein concentration was analyzed using a linear regression model adjusted for sex and age. To confirm the test results, soluble P-selectin was determined using enzyme-linked immunosorbent assay (ELISA) in above mentioned patients and an additional second data set (n = 49). HIT was defined as a positive heparin-induced platelet activation assay (washed platelet assay). Among 98 patients of the primary data set, the median 4Ts score was 5 in patients with HIT, 4 in patients with positive H/PF4 antibodies, and 3 in patients without HIT. The median optical density of a polyspecific H/PF4 ELISA were 3.0, 0.9, and 0.3. Soluble P-selectin remained statistically significant after multiple test adjustments. The area under the receiver operating characteristic curve was 0.81 for Olink and 0.8 for ELISA. Future studies shall assess the diagnostic and prognostic value of soluble P-selectin in the management of HIT.
Electronic and structural properties of Möbius boron-nitride and carbon nanobelts
Authors: Aguiar C. , Dattani N. , Camps I.
Published: April 2024

For the development of nanofilters and nanosensors, we wish to know the impact of size on their geometric, electronic, and thermal stabilities. Using the semiempirical tight binding method as implemented in the xTB program, we characterized Möbius boron-nitride and carbon-based nanobelts with different sizes and compared them to each other and to normal nanobelts. The calculated properties include the infrared spectra, the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO), the energy gap, the chemical potential, and the molecular hardness. The agreement between the peak positions from theoretical infrared spectra compared with experimental ones for all systems validates the methodology that we used. Our findings show that for the boron-nitride-based nanobelts, the calculated properties have an opposite monotonic relationship with the size of the systems, whereas for the carbon-based nanobelts, the properties show the same monotonic relationship for both types of nanobelts. Also, the torsion presented on the Möbius nanobelts, in the case of boron-nitride, induced an inhomogeneous surface distribution for the HOMO orbitals. High-temperature molecular dynamics also allowed us to contrast carbon-based systems with boron-nitride systems at various temperatures. In all cases, the properties vary with the increase in size of the nanobelts, indicating that it is possible to choose the desired values by changing the size and type of the systems. This work has many implications for future studies, for example our results show that carbon-based nanobelts did not break as we increased the temperature, whereas boron-nitride nanobelts had a rupture temperature that varied with their size; this is a meaningful result that can be tested when the use of more accurate simulation methods become practical for such systems in the future.
Randomized controlled open-label trial to evaluate prioritization software for the secondary triage of patients in the pediatric emergency department
Authors: Lun Thomas , Schiro Jessica , Cailliau Emeline , Tchokokam Julien , Liber Melany , de Jorna Claire , Martinot Alain , Dubos François
Published: April 2024

Background

The continual increase in patient attendance at the emergency department (ED) is a worldwide health issue. The aim of this study was to determine whether the use of a secondary prioritization software reduces the patients’ median length of stay (LOS) in the pediatric ED.

Methods

A randomized, controlled, open-label trial was conducted over a 30-day period between March 15th and April 23rd 2021 at Lille University Hospital. Work days were randomized to use the patient prioritization software or the pediatric ED’s standard dashboard. All time intervals between admission and discharge were recorded prospectively by a physician not involved in patient care during the study period. The study’s primary endpoint was the LOS in the pediatric ED, which was expected to be 15 min shorter in the intervention group than in the control group. The secondary endpoints were specific time intervals during the stay in the pediatric ED and levels of staff satisfaction.

Results

1599 patients were included: 798 in the intervention group and 801 in the control group. The median [interquartile range] LOS was 172 min [113–255] in the intervention group and 167 min [108–254) in the control group (p = 0.46). In the intervention group, the time interval between admission to the first medical evaluation for high-priority patients and the time interval between the senior physician’s final evaluation and patient discharge were shorter (p < 0.01). The median satisfaction score was 68 [55–80] (average).

Conclusion

The patients’ total LOS was not significantly shorter on days of intervention. However, use of the electronic patient prioritization tool was associated with significant decreases in some important time intervals during care in the pediatric ED.

ClinicalTrials.gov: NCT05994196

Trial registration number: NCT05994196. Date of registration: August 16th, 2023
Improving strawberry plant resilience to salinity and alkalinity through the use of diverse spectra of supplemental lighting
Authors: Malekzadeh Mohammad Reza , Roosta Hamid Reza , Esmaeilizadeh Majid , Dabrowski Piotr , Kalaji Hazem M.
Published: April 2024

Background

This study explores the impact of various light spectra on the photosynthetic performance of strawberry plants subjected to salinity, alkalinity, and combined salinity/alkalinity stress. We employed supplemental lighting through Light-emitting Diodes (LEDs) with specific wavelengths: monochromatic blue (460 nm), monochromatic red (660 nm), dichromatic blue/red (1:3 ratio), and white/yellow (400–700 nm), all at an intensity of 200 µmol m-2 S-1. Additionally, a control group (ambient light) without LED treatment was included in the study. The tested experimental variants were: optimal growth conditions (control), alkalinity (40 mM NaHCO3), salinity (80 mM NaCl), and a combination of salinity/alkalinity.

Results

The results revealed a notable decrease in photosynthetic efficiency under both salinity and alkalinity stresses, especially when these stresses were combined, in comparison to the no-stress condition. However, the application of supplemental lighting, particularly with the red and blue/red spectra, mitigated the adverse effects of stress. The imposed stress conditions had a detrimental impact on both gas exchange parameters and photosynthetic efficiency of the plants. In contrast, treatments involving blue, red, and blue/red light exhibited a beneficial effect on photosynthetic efficiency compared to other lighting conditions. Further analysis of JIP-test parameters confirmed that these specific light treatments significantly ameliorated the stress impacts.

Conclusions

In summary, the utilization of blue, red, and blue/red light spectra has the potential to enhance plant resilience in the face of salinity and alkalinity stresses. This discovery presents a promising strategy for cultivating plants in anticipation of future challenging environmental conditions.
Development and validation of a scale for the assessment of the knowledge-attitude-practice of parents towards children snoring
Authors: Guo Siyan , Hu Xiaoyue , Wang Xiaokai , Tie Hongyan , Zhang Qiujun , Li Caixia , Qin Luying , Su Hongxia
Published: April 2024

Background

Children Snoring is a common childhood disorder that affects the growth and development of children and is detrimental to their health. Increasing awareness of Children Snoring among parents is important.

Aim

To develop the Knowledge-Attitude-Practice of Parents towards Children Snoring Scale and test the reliability and validity of the scale.

Methods

The development of the tool was divided into two phases involving 1257 parents from China. In the first phase, an initial project bank was created through a literature review. This was followed by a Delphi expert consultation, group discussion and pre-survey. The second stage screened the items and conducted an exploratory factor analysis, then conducted a confirmatory factor analysis and tested for reliability and validity.

Results

Support was found for the 25-item Knowledge-Attitude-Practice toward Children Snoring scale. Exploratory and confirmatory factor analyses provide support for four subscales: (parental basic cognition toward Children Snoring; parents’ perception of complications of Children Snoring; parents’ attitude towards Children Snoring; parents’ concern and prevention of Children Snoring). Internal consistency for the total scale was high (Cronbach’s α = 0.93). The intraclass correlation coefficient of test-retest reliability was 0.92 (95%CI: 0.85 to 0.95), which provided support for the stability of the scale.

Conclusion

The Knowledge-Attitude-Practice of Parents towards Children Snoring scale shows promise as a measure that may be used by medical workers and community children’s health managers.
Analysis of the chain mediation effect between intergenerational support and mental health of older adults in urban China: a structural equation model
Authors: Xu Jiahong , Wang Youwei , Cheung Justin C. , Yin Yanlong
Published: April 2024

Background

This study aimed investigate the impact of intergenerational support on the mental health of older adults in urban China. It also sought to evaluate the chain mediation effect of attitudes toward younger people and willingness to interact with younger people within a non-familial context between intergenerational support and mental health.

Methods

Data were derived from a community survey that adopted quota sampling in mainland China in 2022 (N = 780). Structural equation modeling was used to analyze the data, and the bootstrap technique was used to test the mediation effect.

Results

A significant positive association was found between intergenerational support and the mental health of older adults in urban China (B = 0.852, 95% confidence interval CI [0.157,1.617]). Intergenerational support had a specific indirect effect on mental health through older adults’ attitudes toward younger people within a non-familial context (B = 0.665, 95% CI [0.443,1.046]). There was a chain mediation effect (B = 0.126, 95% CI [0.069,0.224]) in relation to attitudes toward younger people and the willingness to interact with younger people between intergenerational support and mental health. Mediation accounted for 44.44% of the total effects in the model.

Conclusion

These findings help identify modifiable factors that can improve the mental health of older adults. In line with the proposed serial multiple mediation model, this study provides theoretical and practical insights concerning the synergistic effect of intergenerational support at the family level and intergenerational interaction at the community level. Policy and social service implications are also discussed.
Does post acute care reduce the mortality of octogenarian and nonagenarian patients undergoing hip fracture surgery?
Authors: Chiang Yu-Wei , Chang Yu-Jun , Huang Hui-Jen , Hsieh Cheng-Pu , Lu Yueh-Hsiu
Published: April 2024

Background

With the increasing number of elderly individuals worldwide, a greater number of people aged 80 years and older sustain fragility fracture due to osteopenia and osteoporosis.

Methods

This retrospective study included 158 older adults, with a median age of 85 (range: 80–99) years, who sustained hip fragility fracture and who underwent surgery. The patients were divided into two groups, one including patients who joined the post-acute care (PAC) program after surgery and another comprising patients who did not. The mortality, complication, comorbidity, re-fracture, secondary fracture, and readmission rates and functional status (based on the Barthel index score, numerical rating scale score, and Harris Hip Scale score) between the two groups were compared.

Results

The patients who presented with fragility hip fracture and who joined the PAC rehabilitation program after the surgery had a lower rate of mortality, readmission rate, fracture (re-fracture and secondary fracture), and complications associated with fragility fracture, such as urinary tract infection, cerebrovascular accident, and pneumonia (acute coronary syndrome, out-of-hospital cardiac arrest, or in-hospital cardiac arrest.

Conclusions

PAC is associated with a lower rate of mortality and complications such as urinary tract infection, bed sore, and pneumonia in octogenarian and nonagenarian patients with hip fragility fracture.
Association of haemato-biochemical indices and blood composite ratios with microfilaridermia in Onchocerciasis patients
Authors: Debrah Linda Batsa , Gyasi Charles , Ahiadorme Monica , Rahamani Abu Abudu , Opoku Vera Serwaa , Obeng Prince , Osei-Mensah Jubin , Obeng Michael Agyemang , Mensah Derrick Adu , Debrah Alexander Yaw
Published: April 2024

Background

Onchocerciasis causes chronic systemic inflammation. Several studies have used markers such as haemato-biochemical indices to predict the occurrence of systemic inflammation. This study assessed the variability and predictability of haemato-biochemical indices and blood composite ratios (BCRs) in microfilariae positive (MF+) and microfilariae negative (MF-) subgroups of onchocercomata participants.

Methods

One hundred and five (105) MF + and 34 MF- participants were retrospectively recruited into the study. Screening for the presence of O. volvulus microfilariae was done from skin snips taken from the left and right iliac crests of participants using established and approved protocols. Haematological and biochemical indices were measured using standard laboratory automated analyzers. Blood composite ratios (BCRs) were calculated as ratios of the absolute parameters involved.

Results

A significantly increased total WBC, absolute eosinophil, eosinophil percent and absolute basophil were observed in the MF + participants compared to MF- participants. Reduced gamma-glutamyl transferase (GGT) with increased estimated glomerular filtration rate (eGFR) was significantly associated with MF + participants compared to MF- participants. BCRs were significantly higher for eosinophil-to-neutrophil ratio (ENR), eosinophil-to-monocyte ratio (EMR), eosinophil-to-basophil ratio (EBR) and eosinophil-to-lymphocyte ratio (ELR) in MF + participants compared to MF- participants. After multivariate adjustment, onchocercomata participants with increased eosinophil counts (aOR = 13.86, 95% CI [2.07–92.90], p = 0.007), ENR x10 (aOR = 1.42, 95% CI [1.05–1.93], p = 0.025), EMR (aOR = 2.64, 95% CI [1.25–5.60], p = 0.011), EBR (aOR = 1.07, 95% CI [1.01–1.10], p = 0.020) and ELR x10 (aOR = 1.69, 95% CI [1.14–2.51], p = 0.009) were more likely to have microfilaridermia.

Conclusions

Elevated eosinophil counts with higher ENR, EMR, EBR and ELR levels are significantly associated with microfilaridermia in onchocercomata participants. Combining BCRs with eosinophil count significantly led to an improvement in the conventional model for predicting microfilaridermia.
Attributable mortality of acute kidney injury among critically ill patients with sepsis: a multicenter, retrospective cohort study
Authors: Wang Dong-Hui , Zhao Jin-Chao , Xi Xiu-Ming , Zheng Yue , Li Wen-Xiong
Published: April 2024

Background

Sepsis and acute kidney injury (AKI) are common severe diseases in the intensive care unit (ICU). This study aimed to estimate the attributable mortality of AKI among critically ill patients with sepsis and to assess whether AKI was an independent risk factor for 30-day mortality.

Methods

The information we used was derived from a multicenter prospective cohort study conducted in 18 Chinese ICUs, focusing on septic patients post ICU admission. The patients were categorized into two groups: those who developed AKI (AKI group) within seven days following a sepsis diagnosis and those who did not develop AKI (non-AKI group). Using propensity score matching (PSM), patients were matched 1:1 as AKI and non-AKI groups. We then calculated the mortality rate attributable to AKI in septic patients. Furthermore, a survival analysis was conducted comparing the matched AKI and non-AKI septic patients. The primary outcome of interest was the 30-day mortality rate following the diagnosis of sepsis.

Results

Out of the 2175 eligible septic patients, 61.7% developed AKI. After the application of PSM, a total of 784 septic patients who developed AKI were matched in a 1:1 ratio with 784 septic patients who did not develop AKI. The overall 30-day attributable mortality of AKI was 6.6% (95% CI 2.3 ∼ 10.9%, p = 0.002). A subgroup analysis revealed that the 30-day attributable mortality rates for stage 1, stage 2, and stage 3 AKI were 0.6% (95% CI −5.9 ∼ 7.2%, p = 0.846), 4.7% (95% CI −3.1 ∼ 12.4%, p = 0.221) and 16.8% (95% CI 8.1 ∼ 25.2%, p < 0.001), respectively. Particularly noteworthy was that stage 3 AKI emerged as an independent risk factor for 30-day mortality, possessing an adjusted hazard ratio of 1.80 (95% CI 1.31 ∼ 2.47, p < 0.001).

Conclusions

The overall 30-day attributable mortality of AKI among critically ill patients with sepsis was 6.6%. Stage 3 AKI had the most significant contribution to 30-day mortality, while stage 1 and stage 2 AKI did not increase excess mortality.
Assessing antiviral treatment efficacy and risk factors for severe COVID-19 in kidney transplant recipients during the Omicron subvariant-dominant period: a retrospective study
Authors: Sakaguchi Takashi , Mitsuke Akihiko , Osako Yoichi , Yamada Yasutoshi , Takeyama Himawari , Ogawa Risako , Takahashi Katsuya , Hirohata Yukiko , Yamamoto Sayuri , Arima Junya , Fukumoto Wataru , Sugita Satoshi , Inoguchi Satoru , Matsushita Ryosuke , Yoshino Hirofumi , Tatarano Shuichi , Enokida Hideki
Published: April 2024

Background

Kidney transplant recipients (KTRs) are at risk of severe coronavirus disease 2019 (COVID-19), and even now that Omicron subvariants have become dominant, cases of severe disease are certain to occur. The aims of this retrospective study were to evaluate the efficacy of antiviral treatment for COVID-19 and to identify risk factors for severe disease in KTRs during Omicron subvariant-dominant periods.

Methods

A total of 65 KTRs diagnosed with COVID-19 who received antiviral treatment between July 2022 and September 2023 were analyzed. Mild cases received oral molnupiravir (MP) as outpatient therapy, while moderate or worse cases received intravenous remdesivir (RDV) as inpatient therapy. In principle, mycophenolate mofetil was withdrawn and switched to everolimus. We investigated the efficacy of antiviral treatment and compared the clinical parameters of mild/moderate and severe/critical cases to identify risk factors for severe COVID-19.

Results

Among 65 cases, 49 were mild, 6 were moderate, 9 were severe, and 1 was of critical severity. MP was administered to 57 cases; 49 (86%) improved and 8 (14%) progressed. RDV was administered to 16 cases; 14 (87%) improved and 2 (13%) progressed. Seventeen (26%) cases required hospitalization, and none died. Comparisons of the severe/critical group (n = 10) with the mild/moderate group (n = 55) demonstrated that the severe/critical group had a significantly higher median age (64 vs. 53 years, respectively; p = 0.0252), prevalence of diabetes (70% vs. 22%, respectively; p = 0.0047) and overweight/obesity (40% vs. 11%, respectively; p = 0.0393), as well as a significantly longer median time from symptom onset to initial antiviral therapy (3 days vs. 1 day, respectively; p = 0.0026). Multivariate analysis showed that a longer time from symptom onset to initial antiviral treatment was an independent risk factor for severe COVID-19 (p = 0.0196, odds ratio 1.625, 95% confidence interval 1.081–2.441).

Conclusion

These findings suggest that a longer time from symptom onset to initial antiviral treatment is associated with a higher risk of severe COVID-19 in KTRs. Initiating antiviral treatment as early as possible is crucial for preventing severe outcomes; this represents a valuable insight into COVID-19 management in KTRs.
Development and validation of prediction models for papillary thyroid cancer structural recurrence using machine learning approaches
Authors: Wang Hongxi , Zhang Chao , Li Qianrui , Tian Tian , Huang Rui , Qiu Jiajun , Tian Rong
Published: April 2024

Background

Although papillary thyroid cancer (PTC) patients are known to have an excellent prognosis, up to 30% of patients experience disease recurrence after initial treatment. Accurately predicting disease prognosis remains a challenge given that the predictive value of several predictors remains controversial. Thus, we investigated whether machine learning (ML) approaches based on comprehensive predictors can predict the risk of structural recurrence for PTC patients.

Methods

A total of 2244 patients treated with thyroid surgery and radioiodine were included. Twenty-nine perioperative variables consisting of four dimensions (demographic characteristics and comorbidities, tumor-related variables, lymph node (LN)-related variables, and metabolic and inflammatory markers) were analyzed. We applied five ML algorithms—logistic regression (LR), support vector machine (SVM), extreme gradient boosting (XGBoost), random forest (RF), and neural network (NN)—to develop the models. The area under the receiver operating characteristic (AUC-ROC) curve, calibration curve, and variable importance were used to evaluate the models’ performance.

Results

During a median follow-up of 45.5 months, 179 patients (8.0%) experienced structural recurrence. The non-stimulated thyroglobulin, LN dissection, number of LNs dissected, lymph node metastasis ratio, N stage, comorbidity of hypertension, comorbidity of diabetes, body mass index, and low-density lipoprotein were used to develop the models. All models showed a greater AUC (AUC = 0.738 to 0.767) than did the ATA risk stratification (AUC = 0.620, DeLong test: P < 0.01). The SVM, XGBoost, and RF model showed greater sensitivity (0.568, 0.595, 0.676), specificity (0.903, 0.857, 0.784), accuracy (0.875, 0.835, 0.775), positive predictive value (PPV) (0.344, 0.272, 0.219), negative predictive value (NPV) (0.959, 0.959, 0.964), and F1 score (0.429, 0.373, 0.331) than did the ATA risk stratification (sensitivity = 0.432, specificity = 0.770, accuracy = 0.742, PPV = 0.144, NPV = 0.938, F1 score = 0.216). The RF model had generally consistent calibration compared with the other models. The Tg and the LNR were the top 2 important variables in all the models, the N stage was the top 5 important variables in all the models.

Conclusions

The RF model achieved the expected prediction performance with generally good discrimination, calibration and interpretability in this study. This study sheds light on the potential of ML approaches for improving the accuracy of risk stratification for PTC patients.

Trial registration

Retrospectively registered at www.chictr.org.cn (trial registration number: ChiCTR2300075574, date of registration: 2023-09-08).
Pretreatment multiparametric MRI radiomics-integrated clinical hematological biomarkers can predict early rapid metastasis in patients with nasopharyngeal carcinoma
Authors: Cao Xiujuan , Wang Xiaowen , Song Jian , Su Ya , Wang Lizhen , Yin Yong
Published: April 2024

Background

To establish and validate a predictive model combining pretreatment multiparametric MRI-based radiomic signatures and clinical characteristics for the risk evaluation of early rapid metastasis in nasopharyngeal carcinoma (NPC) patients.

Methods

The cutoff time was used to randomly assign 219 consecutive patients who underwent chemoradiation treatment to the training group (n = 154) or the validation group (n = 65). Pretreatment multiparametric magnetic resonance (MR) images of individuals with NPC were employed to extract 428 radiomic features. LASSO regression analysis was used to select radiomic features related to early rapid metastasis and develop the Rad-score. Blood indicators were collected within 1 week of pretreatment. To identify independent risk variables for early rapid metastasis, univariate and multivariate logistic regression analyses were employed. Finally, multivariate logistic regression analysis was applied to construct a radiomics and clinical prediction nomogram that integrated radiomic features and clinical and blood inflammatory predictors.

Results

The NLR, T classification and N classification were found to be independent risk indicators for early rapid metastasis by multivariate logistic regression analysis. Twelve features associated with early rapid metastasis were selected by LASSO regression analysis, and the Rad-score was calculated. The AUC of the Rad-score was 0.773. Finally, we constructed and validated a prediction model in combination with the NLR, T classification, N classification and Rad-score. The area under the curve (AUC) was 0.936 (95% confidence interval (95% CI): 0.901–0.971), and in the validation cohort, the AUC was 0.796 (95% CI: 0.686–0.905).

Conclusions

A predictive model that integrates the NLR, T classification, N classification and MR-based radiomics for distinguishing early rapid metastasis may serve as a clinical risk stratification tool for effectively guiding individual management.
Traumatic terson syndrome with a peculiar mass lesion and tractional retinal detachment: a case report
Authors: Lin Yung-Chen , Wang Chung-Ting , Chen Kuan-Jen , Chou Hung-Da
Published: April 2024

Background

To report a case with bilateral Terson syndrome presented with a unique mushroom-like mass lesion on the optic disc along with proliferative vitreoretinopathy and tractional retinal detachment.

Case presentation

A 33-year-old man was injured during a traffic accident and had diffuse brain swelling and intraocular hemorrhage. Poor vision in both eyes was noted after the patient regained consciousness. B-scan ultrasonography showed extensive vitreous opacity with a posterior vitreous detachment and without obvious retinal detachment. Vitrectomy was performed in both eyes five months after the accident. After clearing up the vitreous opacity, a peculiar pigmented mushroom-like mass lesion was noted in the posterior pole and had severe adhesion to the underneath optic disc. Extensive multilayered peripapillary epiretinal membrane was found covering the posterior pole and led to tractional retinal detachment around the macula. The mass was presumed to be an organized vitreous hemorrhage originated from the optic disc. The extensive and adherent epiretinal membrane together with the mass lesion were removed as much as possible and silicon oil was injected for tamponade. However, in the right eye, the retina redetached under silicon oil, whereas in the left eye, his vision improved to 20/100.

Conclusions

Terson syndrome usually has a favorable prognosis but may be complicated by proliferative vitreoretinopathy and tractional retinal detachment. Careful monitoring is warranted and early vitrectomy should be considered in cases suspecting additional pathologies.
Size estimation of key populations and ‘bridge populations’ based on the network scale-up method in Ukraine
Authors: Kovtun Oksana , Paniotto Volodymyr , Sakhno Yulia , Dumchev Kostyantyn
Published: April 2024

Introduction

Correct estimation of the size of key and bridge populations is crucial for an efficient HIV/AIDS response in resource-limited settings, enabling efficient program planning and resource allocation. The hidden nature of these groups poses challenges to traditional methods, leading to the adoption of innovative approaches like the network scale-up method (NSUM). In this article we present the results of a NSUM study conducted in 2020 in Ukraine, focusing on four key populations and three bridge populations, highlighting challenges and contributions to development of the method.

Methods

From July to September 2020, we conducted a nationally representative survey in Ukraine via computer-assisted telephone interviews, and applied the known population method and summation method to estimate social networks sizes. Results were weighted based on individual sampling probability and adjusted for social respect and visibility factors to address potential limitations.

Results

Our study achieved a 20% response rate with 10,000 completed interviews. The social network size, using the known population method, was 213 people, and 125 using the summation method. Adjusting for the social respect and visibility, estimated key populations sizes were 295,857 [248,714–343,001] people who inject drugs, 152,267 [109,960–194,573] men who have sex with men, 78,385 [57,146–99,619] sex workers, and 9,963 [7,352–12,571] transgender people, detailed by age and gender. Bridge populations were estimated at 62,162 [50,445–73,879] sexual partners of people who inject drugs, 284,348 [233,113–335,583] clients of sex workers, and 13,697 [7,370–20,026] female partners of men who have sex with men.

Conclusions

NSUM proves reliable for estimating key populations size with appropriate corrections. It shows promise for further use in Ukraine, considering limited geographic coverage of the integrated bio-behavioral studies to use multiplier-based methods. However, the validity concerns persist for estimating bridge populations size, emphasizing the need for further method refinement and addressing implementation issues, particularly those related to data collection.
Association of CCND1 rs9344 polymorphism with lung cancer susceptibility and clinical outcomes: a case-control study
Authors: Mei Chao , Wang Tian , Xu Baoli , Wu Sanlan , Zhang Xuelin , Lv Yongning , Zhang Yu , Liu Zhaoqian , Gong Weijing
Published: April 2024

Background

Cyclin D1 (CCND1) plays a pivotal role in cancer susceptibility and the platinum-based chemotherapy response. This study aims to assess the relationship between a common polymorphism (rs9344 G > A) in CCND1 gene with cancer susceptibility, platinum-based chemotherapy response, toxicities and prognosis of patients with lung cancer.

Methods

This study involved 498 lung cancer patients and 213 healthy controls. Among them, 467 patients received at least two cycles of platinum-based chemotherapy. Unconditional logistical regression analysis and meta-analysis were performed to evaluate the associations.

Results

The lung adenocarcinoma risk was significantly higher in patients with AA than GG + GA genotype (adjusted OR = 1.755, 95%CI = 1.057–2.912, P = 0.030). CCND1 rs9344 was significantly correlated with platinum-based therapy response in patients receiving PP regimen (additive model: adjusted OR = 1.926, 95%CI = 1.029–3.605, P = 0.040; recessive model: adjusted OR = 11.340, 95%CI = 1.428–90.100, P = 0.022) and in the ADC subgroups (recessive model: adjusted OR = 3.345, 95%CI = 1.276–8.765, P = 0.014). Furthermore, an increased risk of overall toxicity was found in NSCLC patients (additive model: adjusted OR = 1.395, 95%CI = 1.025–1.897, P = 0.034; recessive model: adjusted OR = 1.852, 95%CI = 1.088–3.152, P = 0.023), especially ADC subgroups (additive model: adjusted OR = 1.547, 95%CI = 1.015–2.359, P = 0.043; recessive model: adjusted OR = 2.030, 95%CI = 1.017–4.052, P = 0.045). Additionally, CCND1 rs9344 was associated with an increased risk of gastrointestinal toxicity in non-smokers (recessive model: adjusted OR = 2.620, 95%CI = 1.083–6.336, P = 0.035). Non-significant differences were observed in the 5-year overall survival rate between CCND1 rs9344 genotypes. A meta-analysis of 5432 cases and 6452 control samples did not find a significant association between lung cancer risk and CCND1 rs9344 polymorphism.

Conclusion

This study suggests that in the Chinese population, CCND1 rs9344 could potentially serve as a candidate biomarker for cancer susceptibility and treatment outcomes in specific subgroups of patients.
Considerations beyond spine pain: do different co-occurring lower body joint pains differentially influence physical function and quality of life ratings?
Authors: McGargill Shawn , Sein Michael , Sibille Kimberly T. , Thompson Zane , Brownstein Michael , Vincent Heather K.
Published: April 2024

Background

Patients seeking medical care for back pain often have coexisting painful joints and the effects of different combinations and number of coexisting pain sites (hip, knee, foot/ankle) to back pain on physical function domains and quality of life rating are not yet established. The purpose of this study was to determine the differences in functional outcomes and QOL among individuals with back pain who have concurrent additional pain sites or no pain sites.

Methods

Data from the Osteoarthritis Initiative (OAI) cohort were used for this cross-sectional analysis. Men and women aged 45–79 years with back pain were binned into nine groups by presence or not of coexisting hip, knee, ankle/foot pain and combinations of these sites (N = 1,642). Healthy controls reported no joint pain. Main outcomes included Knee Injury and Osteoarthritis Outcome score (KOOS; quality of life and function-sports-and-recreation), Western Ontario McMaster Universities Osteoarthritis Index (WOMAC; Activities of Daily Living, Pain), Medical Outcomes Short Form-12 (SF-12) Physical Component score, and self-reported function in last 7–30 days (lifting 25-pound objects, housework). 20-m and 400-m walk times and gait speed and repeated chair rise test times were collected.

Results

Compared to back pain alone, pain at all five sites was associated with 39%—86% worse KOOS, WOMAC, and SF-12 scores (p < .0001). Back-Hip and Back-Knee did not produce worse scores than Back pain alone, but Back-Hip-Knee and Back-Knee-Ankle/Foot did. The 20-m, 400-m walk, and repeated chair times were worse among individuals with pain at all five sites. Additional hip and knee sites to back pain, but not ankle/foot, worsened performance-based walk times and chair rise scores.

Conclusions

The number and type of coexistent lower body musculoskeletal pain among patients with back pain may be associated with perceived and performance-based assessments. Management plans that efficiently simultaneously address back and additional coexistent pain sites may maximize treatment functional benefits, address patient functional goals in life and mitigate disability.
Which factors predict tumor recurrence and survival after curative hepatectomy in hepatocellular carcinoma? Results from a European institution
Authors: Vaghiri Sascha , Prassas Dimitrios , Mustafov Onur , Kalmuk Sinan , Knoefel Wolfram Trudo , Lehwald-Tywuschik Nadja , Alexander Andrea , Dizdar Levent
Published: April 2024

Background

High tumor recurrence and dismal survival rates after curative intended resection for hepatocellular carcinoma (HCC) are still concerning. The primary goal was to assess predictive factors associated with disease-free (DFS) and overall survival (OS) in a subset of patients with HCC undergoing hepatic resection (HR).

Methods

Between 08/2004–7/2021, HR for HCC was performed in 188 patients at our institution. Data allocation was conducted from a prospectively maintained database. The prognostic impact of clinico-pathological factors on DFS and OS was assessed by using uni- and multivariate Cox regression analyses. Survival curves were generated with the Kaplan Meier method.

Results

The postoperative 1-, 3- and 5- year overall DFS and OS rates were 77.9%, 49.7%, 41% and 72.7%, 54.7%, 38.8%, respectively. Tumor diameter ≥ 45 mm [HR 1.725; (95% CI 1.091–2.727); p = 0.020], intra-abdominal abscess [HR 3.812; (95% CI 1.859–7.815); p < 0.0001], and preoperative chronic alcohol abuse [HR 1.831; (95% CI 1.102–3.042); p = 0.020] were independently predictive for DFS while diabetes mellitus [HR 1.714; (95% CI 1.147–2.561); p = 0.009), M-Stage [HR 2.656; (95% CI 1.034–6.826); p = 0.042], V-Stage [HR 1.946; (95% CI 1.299–2.915); p = 0.001, Sepsis [HR 10.999; (95% CI 5.167–23.412); p < 0.0001], and ISGLS B/C [HR 2.008; (95% CI 1.273–3.168); p = 0.003] were significant determinants of OS.

Conclusions

Despite high postoperative recurrence rates, an acceptable long-term survival in patients after curative HR could be achieved. The Identification of parameters related to OS and DFS improves patient-centered treatment and surveillance strategies.
Single-port plus one in pediatric robotic-assisted Lich-Gregoir ureteral reimplantation for vesicoureteral reflux, a comparative analysis with short-term outcomes
Authors: Chen Jianglong , Kang Yingquan , Lin Shan , He Shaohua , He Yufeng , Xu Xinru , Xu Huihuang , You Guangxu , Xu Di
Published: April 2024

Objective

To observe the safety and short-term outcomes of a new way of laparoscopic trocar placement in pediatric robotic-assisted Lich-Gregoir ureteral reimplantation for vesicoureteral reflux.

Methods

The retrospective study included 32 patients under 14 years diagnosed with primary vesicoureteral reflux (VUR). All these patients underwent robotic-assisted Lich-Gregoir ureteral reimplantation in our department from December 2020 to August 2022. These patients were divided into the following groups according to the different ways of trocar placement: 13 patients in group single-port plus one (SR) and 19 patients in group multiple-port (MR). Patients’ characteristics as well as their perioperative and follow-up data were collected and evaluated.

Results

There was no significant difference in the data regarding patients’ characteristics and preoperative data. These data included the grade of vesicoureteral reflux according to the voiding cystourethrogram (VCUG), and the differential degree of renal function (DRF) at the following time points: preoperative, postoperative, and comparison of preoperative and postoperative. There was no difference between the two groups. During surgery, the time of artificial pneumoperitoneum establishment, ureteral reimplantation time, and total operative time in the SR group were longer than those in the MR group. Yet only the time of artificial pneumoperitoneum establishment shows a statistical difference (P < 0.0001). Also, the peri-operative data, including the volume of blood loss, fasting time, hospitalization, and length of time that a ureteral catheter remained in place, and the number of postoperative complications demonstrate no difference. In addition, the SFU grade and VCUG grade at the following time point also show no difference between the two groups.

Conclusion

The study demonstrates that SR in robotic-assisted Lich-Gregoir ureteral reimplantation has reached the same surgical effects as MR. In addition, the single-port plus one trocar placement receives a higher cosmetic satisfaction score from parents and did not increase the surgical time and complexity.
Occupational therapy students' perceptions of their experience in a role-emerging Level II fieldwork within higher education student services
Authors: Potvin Marie-Christine , Morales Alexis N. , West Erin K. , Kalimi Mika , Coviello Jeanne M.
Published: April 2024

Background

Role-emerging settings – those where occupational therapy (OT) services have not traditionally been provided – are common sites for practice placements of entry-level occupational therapy students. A growing body of literature has attempted to determine the value and drawbacks of such practice placements on the professional preparedness of OT students with mixed findings. Benefits have been identified, including increased cultural understanding, advocacy, creativity, initiative, and problem-solving skills. However, OT students have been reported to perceive such placement as limiting their professional growth and preparedness to practice compared to traditional placements.

Methods

A phenomenological study was conducted seeking the perceptions of OT students (n = 14) about their clinical placement at a role-emerging site. Recorded semi-structured interviews were conducted by trained interviewers within two weeks of the end of clinical placement. The recordings were transcribed verbatim and then coded using an iterative multi-coder inductive approach. Inter-coder agreement, reflectivity, and audit trail were maintained.

Results

Three themes emerged from the analysis: (1) integrating independence and support, (2) becoming occupational therapists, and (3) filling a gap. These themes reflect students’ positive perceptions of their role-emerging clinical placement. They felt that this placement allowed them to develop self-confidence and professional identity as occupational therapists and learn new skills while simultaneously filling a gap in services for clients. Most importantly, they felt that this placement prepared them for their future OT practice.

Conclusion

This finding and their resounding support of the experience suggest that OT students can perceive role-emerging placement as a solid foundation for clinical practice. Factors, included in this placement, that may have contributed to their experience include the level of support provided, time available for learning including space to make mistakes, and freedom from productivity and payor requirements.
Alkylated EDTA potentiates antibacterial photodynamic activity of protoporphyrin
Authors: Piao Ying , Himbert Sebastian , Li Zifan , Liu Jun , Zhao Zhihao , Yu Huahai , Liu Shuangshuang , Shao Shiqun , Fefer Michael , Rheinstädter Maikel C. , Shen Youqing
Published: April 2024

Antibiotic resistance has garnered significant attention due to the scarcity of new antibiotics in development. Protoporphyrin IX (PpIX)-mediated photodynamic therapy shows promise as a novel antibacterial strategy, serving as an alternative to antibiotics. However, the poor solubility of PpIX and its tendency to aggregate greatly hinder its photodynamic efficacy. In this study, we demonstrate that alkylated EDTA derivatives (aEDTA), particularly C14-EDTA, can enhance the solubility of PpIX by facilitating its dispersion in aqueous solutions. The combination of C14-EDTA and PpIX exhibits potent antibacterial activity against Staphylococcus aureus (S. aureus) when exposed to LED light irradiation. Furthermore, this combination effectively eradicates S. aureus biofilms, which are known to be strongly resistant to antibiotics, and demonstrates high therapeutic efficacy in an animal model of infected ulcers. Mechanistic studies reveal that C14-EDTA can disrupt PpIX crystallization, increase bacterial membrane permeability and sequester divalent cations, thereby improving the accumulation of PpIX in bacteria. This, in turn, enhances reactive oxygen species (ROS) production and the antibacterial photodynamic activity. Overall, this effective strategy holds great promise in combating antibiotic-resistant strains.

Graphical Abstract
Biointerfaces with ultrathin patterns for directional control of cell migration
Authors: Cheng Yijun , Pang Stella W.
Published: April 2024

In the context of wound healing and tissue regeneration, precise control of cell migration direction is deemed crucial. To address this challenge, polydimethylsiloxane (PDMS) platforms with patterned 10 nm thick TiOx in arrowhead shape were designed and fabricated. Remarkably, without tall sidewall constraints, MC3T3-E1 cells seeded on these platforms were constrained to migrate along the tips of the arrowheads, as the cells were guided by the asymmetrical arrowhead tips which provided large contact areas. To the best of our knowledge, this is the first study demonstrating the use of thin TiOx arrowhead pattern in combination with a cell-repellent PDMS surface to provide guided cell migration unidirectionally without tall sidewall constraints. Additionally, high-resolution fluorescence imaging revealed that the asymmetrical distribution of focal adhesions, triggered by the patterned TiOx arrowheads with arm lengths of 10, 20, and 35 μm, promoted cell adhesion and protrusion along the arrowhead tip direction, resulting in unidirectional cell migration. These findings have important implications for the design of biointerfaces with ultrathin patterns to precisely control cell migration. Furthermore, microelectrodes were integrated with the patterned TiOx arrowheads to enable dynamic monitoring of cell migration using impedance measurement. This microfluidic device integrated with thin layer of guiding pattern and microelectrodes allows simultaneous control of directional cell migration and characterization of the cell movement of individual MC3T3-E1 cells, offering great potential for the development of biosensors for single-cell monitoring.