bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumour microenvironment as a predictive factor for immunotherapy in non-muscle-invasive bladder cancer
Authors: Semeniuk-Wojtaś Aleksandra , Poddębniak-Strama Karolina , Modzelewska Magdalena , Baryła Maksymilian , Dziąg-Dudek Ewelina , Syryło Tomasz , Górnicka Barbara , Jakieła Anna , Stec Rafał
Published: March 2023

Bladder cancer (BC) can be divided into two subgroups depending on invasion of the muscular layer: non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). Its aggressiveness is associated, inter alia, with genetic aberrations like losses of 1p, 6q, 9p, 9q and 13q; gain of 5p; or alterations in the p53 and p16 pathways. Moreover, there are reported metabolic disturbances connected with poor diagnosis—for example, enhanced aerobic glycolysis, gluconeogenesis or haem catabolism.

Currently, the primary way of treatment method is transurethral resection of the bladder tumour (TURBT) with adjuvant Bacillus Calmette–Guérin (BCG) therapy for NMIBC or radical cystectomy for MIBC combined with chemotherapy or immunotherapy. However, intravesical BCG immunotherapy and immune checkpoint inhibitors are not efficient in every case, so appropriate biomarkers are needed in order to select the proper treatment options. It seems that the success of immunotherapy depends mainly on the tumour microenvironment (TME), which reflects the molecular disturbances in the tumour. TME consists of specific conditions like hypoxia or local acidosis and different populations of immune cells including tumour-infiltrating lymphocytes, natural killer cells, neutrophils and B lymphocytes, which are responsible for shaping the response against tumour neoantigens and crucial pathways like the PD-L1/PD-1 axis.

In this review, we summarise holistically the impact of the immune system, genetic alterations and metabolic changes that are key factors in immunotherapy success. These findings should enable better understanding of the TME complexity in case of NMIBC and causes of failures of current therapies.
The outcomes of total hip replacement in osteonecrosis versus osteoarthritis: a systematic review and meta-analysis
Authors: Salman Loay A. , Hantouly Ashraf T. , Khatkar Harman , Al-Ani Abdallah , Abudalou Abedallah , Al-Juboori Mohammed , Ahmed Ghalib
Published: March 2023

Purpose

This systematic review and meta-analysis aimed to compare the outcomes of THA in patients with osteonecrosis (ON) and those with osteoarthritis (OA).

Methods

Four databases were searched from inception till December 2022 for original studies that compared the outcomes of THA in ON and OA. The primary outcome was the revision rate; the secondary outcomes were dislocation and Harris hip score. This review was conducted in line with PRISMA guidelines, and the risk of bias was assessed using the Newcastle–Ottawa scale.

Results

A total of 14 observational studies with 2,111,102 hips were included, with a mean age of 50.83 ± 9.32 and 55.51 ± 8.95 for ON and OA groups, respectively. The average follow-up was 7.25 ± 4.6 years. There was a statistically significant difference in revision rate between ON and OA patients in favour of OA (OR: 1.576; 95%CI: 1.24–2.00; p-value: 0.0015). However, dislocation rate (OR: 1.5004; 95%CI: 0.92–2.43; p-value: 0.0916) and Haris hip score (HHS) (SMD: − 0.0486; 95%CI: − 0.35–0.25; p-value: 0.6987) were comparable across both groups. Further sub-analysis adjusting for registry data also showed similar results between both groups.

Conclusion

A higher revision rate, periprosthetic fracture and periprosthetic joint infection following total hip arthroplasty were associated with osteonecrosis of the femoral head compared with osteoarthritis. However, both groups had similar dislocation rates and functional outcome measures. This finding should be applied in context due to potential confounding factors, including patient’s age and activity level.
Israeli Female Physicians' Motives for Choosing Orthopedics as Their Specialty Choice
Authors: Yonai Yaniv , Masarwa Rawan , Steinfeld Yaniv , Ben Natan Merav , Berkovich Yaron
Published: March 2023

Background

Orthopedics is not a popular field of specialization among female medical students. Therefore, the purpose of the study was to examine factors related to women's choice of orthopedics as their field of specialty, compared to those who chose other fields.

Methods

In this cross‐sectional survey, 149 female medical residents from Israel—33 specializing in orthopedics and 116 in other fields—completed a questionnaire. A comparison was held between the two groups.

Results

Orthopedic residents were more likely to have received clinical training in this field during their medical studies and were more likely to have expressed a desire to specialize in orthopedics before and at the completion of their studies. In addition, orthopedic residents ascribed greater importance to job security when choosing a field of specialty and, in contrast, ascribed no importance at all to lifestyle. No difference was found between the two groups in their level of dissatisfaction as a result of their residency. However, orthopedic residents were more inclined to perceive gender discrimination in the field of orthopedics but, despite this, had a greater intention to recommend a residency in orthopedics. A negative association was found between the level of dissatisfaction as a result of the residency and intention to recommend a residency in orthopedics.

Conclusions

Differences between the two groups point to potential factors that might have been related to women's choice of orthopedics as their field of specialty. The findings may help form strategies for attracting women to specialize in orthopedics.
In‐Hospital Obstetric Delays in Rural Uganda: A Cross‐Sectional Analysis of a Hospital Cohort
Authors: Poppens McKayla , Oke Rasheedat , Carvalho Melissa , Ledesma Yeranui , Okullu Silas , Ariokot Mary Goretty , Agwang Esther , Ekuchu Peter , Wange Hyginus , Boeck Marissa , Juillard Catherine , Ajiko Mary Margaret , Dicker Rochelle
Published: March 2023

Background

Deaths related to pregnancy and childbirth are extremely high in low‐resource countries such as Uganda. Maternal mortality in low‐ and middle‐income countries is related to delays in seeking, reaching, and receiving adequate health care. This study aimed to investigate the in‐hospital delays to surgical care for women in labor arriving to Soroti Regional Referral Hospital (SRRH).

Methods

From January 2017 to August 2020, we collected data on obstetric surgical patients in labor using a locally developed, context‐specific obstetrics surgical registry. Data regarding patient demographics, clinical and operative characteristics, as well as delays in care and outcomes were documented. Descriptive and multivariate statistical analyses were conducted.

Results

A total of 3189 patients were treated during our study period. Median age was 23 years, most gestations were at term (97%) at the time of operation, and nearly all patients underwent Cesarean Section (98.8%). Notably, 61.7% of patients experienced at least one delay in their surgical care at SRRH. Lack of surgical space was the greatest contributor to delay (59.9%), followed by lack of supplies or personnel. The significant independent predictors of delayed care were having a prenatal acquired infection (AOR 1.73, 95% CI 1.43–2.09) and length of symptoms less than 12 h (AOR 0.32, 95% CI 0.26–0.39) or greater than 24 h (AOR 2.61, 95% CI 2.18–3.12).

Conclusion

In rural Uganda, there is a significant need for financial investment and commitment of resources to expand surgical infrastructure and improve care for mothers and neonates.
G6PD deficiency—does it alter the course of COVID-19 infections?
Authors: Au Tsz Yuen , Wiśniewski Oskar Wojciech , Benjamin Shamiram , Kubicki Tadeusz , Dytfeld Dominik , Gil Lidia
Published: March 2023

Despite the existence of well-founded data around the relationship between reactive oxygen species (ROS) and glucose-6-phosphate dehydrogenase (G6PD), current research around G6PD-deficient patients with viral infections, and limitations as a result of their condition, are inadequate. Here, we analyze existing data around immunological risks, complications, and consequences of this disease, particularly in relation to COVID-19 infections and treatment. The relationship between G6PD deficiency and elevated ROS leading to increased viral load suggests that these patients may confer heightened infectivity. Additionally, worsened prognoses and more severe complications of infection may be realized in class I G6PD-deficient individuals. Though more research is demanded on the topic, preliminary studies suggest that antioxidative therapy which reduces ROS levels in these patients could prove beneficial in the treatment of viral infections in G6PD-deficient individuals.
Klassifikation aggressiver B-Zell-Lymphome
Authors: Rosenwald Andreas , Menter Thomas , Dirnhofer Stefan
Published: March 2023

Die 5. Edition der WHO-Klassifikation maligner Lymphome (WHO-HAEM5) und die Internationale Konsensus-Klassifikation (ICC) zeigen, was die Einteilung aggressiver B‑Zell-Lymphome angeht, erfreulicherweise nur wenige Unterschiede, die unseren diagnostischen Alltag wenig beeinflussen dürften. Auch die Neuerungen gegenüber der revidierten WHO-Klassifikation aus dem Jahr 2017 (WHO-HAEM4R) sind moderat. Sie betreffen meist geringfügige Namensänderungen einzelner Entitäten, Anpassung diagnostischer Kriterien oder eine Aufwertung „provisorischer“ zu „distinkten“ Entitäten. Die Definition des häufigsten aggressiven B‑Zell-Lymphoms, des diffus großzellige B‑Zell-Lymphom, nicht anderweitig klassifiziert (DLBCL, NOS), bleibt unverändert, eine Unterteilung in den Keimzentrumstyp bzw. Nicht-Keimzentrumstyp sehen beide Klassifikationen als wichtig an. Das DLBCL, NOS, muss im Rahmen der Routinediagnostik von anderen großzelligen B‑Zell-Lymphomen abgegrenzt werden. Dazu zählen das großzellige B‑Zell-Lymphom mit IRF4-Rearrangement, das in der ICC und WHO-HAEM5 zu einer definitiven Entität hochgestuft wurde, und das großzellige bzw. high-grade B‑Zell-Lymphom mit 11q-Aberration. Aggressive B‑Zell-Lymphome mit MYC- und BCL2-Rearrangement stellen biologisch eine homogene Gruppe dar und werden in beiden Klassifikationen als definitive Entitäten gelistet. Dies gilt nicht für die sehr heterogene Gruppe aggressiver Lymphome mit MYC- und BCL6-Rearrangements, welche von der ICC als provisorische Entität anerkannt werden, während die WHO-HAEM5 diese entweder unter den DLBCL, NOS oder den hochmalignen B‑Zell-Lymphomen, nicht anderweitig spezifiziert (HGBL, NOS), listet.
Quantification of airway wall contrast enhancement on virtual monoenergetic images from spectral computed tomography
Authors: Bodenberger Arndt Lukas , Konietzke Philip , Weinheimer Oliver , Wagner Willi Linus , Stiller Wolfram , Weber Tim Frederik , Heussel Claus Peter , Kauczor Hans-Ulrich , Wielpütz Mark Oliver
Published: March 2023

Objectives

Quantitative computed tomography (CT) plays an increasingly important role in phenotyping airway diseases. Lung parenchyma and airway inflammation could be quantified by contrast enhancement at CT, but its investigation by multiphasic examinations is limited. We aimed to quantify lung parenchyma and airway wall attenuation in a single contrast-enhanced spectral detector CT acquisition.

Methods

For this cross-sectional retrospective study, 234 lung-healthy patients who underwent spectral CT in four different contrast phases (non-enhanced, pulmonary arterial, systemic arterial, and venous phase) were recruited. Virtual monoenergetic images were reconstructed from 40–160 keV, on which attenuations of segmented lung parenchyma and airway walls combined for 5th–10th subsegmental generations were assessed in Hounsfield Units (HU) by an in-house software. The spectral attenuation curve slope between 40 and 100 keV (λHU) was calculated.

Results

Mean lung density was higher at 40 keV compared to that at 100 keV in all groups (p < 0.001). λHU of lung attenuation was significantly higher in the systemic (1.7 HU/keV) and pulmonary arterial phase (1.3 HU/keV) compared to that in the venous phase (0.5 HU/keV) and non-enhanced (0.2 HU/keV) spectral CT (p < 0.001). Wall thickness and wall attenuation were higher at 40 keV compared to those at 100 keV for the pulmonary and systemic arterial phase (p ≤ 0.001). λHU for wall attenuation was significantly higher in the pulmonary arterial (1.8 HU/keV) and systemic arterial (2.0 HU/keV) compared to that in the venous (0.7 HU/keV) and non-enhanced (0.3 HU/keV) phase (p ≤ 0.002).

Conclusions

Spectral CT may quantify lung parenchyma and airway wall enhancement with a single contrast phase acquisition, and may separate arterial and venous enhancement. Further studies are warranted to analyze spectral CT for inflammatory airway diseases.

Key Points

• Spectral CT may quantify lung parenchyma and airway wall enhancement with a single contrast phase acquisition.

• Spectral CT may separate arterial and venous enhancement of lung parenchyma and airway wall.

• The contrast enhancement can be quantified by calculating the spectral attenuation curve slope from virtual monoenergetic images.
Virtual monochromatic images for coronary artery imaging with a spectral photon-counting CT in comparison to dual-layer CT systems: a phantom and a preliminary human study
Authors: Greffier Joel , Si-Mohamed Salim A. , Lacombe Hugo , Labour Joey , Djabli Djamel , Boccalini Sara , Varasteh Mohammad , Villien Marjorie , Yagil Yoad , Erhard Klaus , Boussel Loic , Beregi Jean-Paul , Douek Philippe C.
Published: March 2023

Objectives

To evaluate the quality of virtual monochromatic images (VMIs) from spectral photon-counting CT (SPCCT) and two energy-integrating detector dual-energy CT (EID-DECT) scanners from the same manufacturer, for the coronary lumen.

Methods

A 21-cm section of the Mercury v4.0 phantom was scanned using a cardiac CT protocol. VMIs from 40 to 90 keV were reconstructed using high-resolution (HR) parameters for EID-DECT and SPCCT (CB and HRB kernels at 0.67 mm slice thickness, respectively). Ultra-high-resolution (UHR) parameters were used in addition to SPCCT (detailed-2 kernel, 0.43 mm slice thickness). Noise-power-spectrum (NPS), task-based transfer function (TTF), and detectability index (d′) were computed for 2-mm-diameter lumen detection. In consensus, two radiologists analyzed the quality of the images from 8 patients who underwent coronary CTA on both CT systems.

Results

For all keV images, fpeak, f50, and d′ were higher with SPCCT. The fpeak and f50 were higher with UHR-SPCCT with greater noise and lower d′ compared to those of the HR-SPCCT images. Noise magnitude was constant for all energy levels (keV) with both systems, and lower with HR images, and d′ decreased as keV decreased. Subjective analysis showed greater lumen sharpness and overall quality for HR and UHR-SPCCT images using all keV, with a greater difference at low keV compared to HR-EID-DECT images.

Conclusion

HR and UHR-SPCCT images gave greater detectability of the coronary lumen for 40 to 90 keV VMIs compared to two EID-DECT systems, with benefits of higher lumen sharpness and overall quality.

Key Points

• Compared with 2 dual-energy CT systems, spectral photon-counting CT (SPCCT) improved spatial resolution, noise texture, noise magnitude, and detectability of the coronary lumen.

• Use of ultra-high-resolution parameters with SPCCT improved spatial resolution and noise texture and provided high detectability of the coronary lumen, despite an increase in noise magnitude.

• In eight patients, radiologists found greater overall image quality with SPCCT for all virtual monochromatic images with a greater difference at low keV, compared with dual-energy CT systems.
Infliximab response associates with radiologic findings in bio-naïve Crohn’s disease
Authors: Yueying Chen , Jing Feng , Qi Feng , Jun Shen
Published: March 2023

Objectives

Since a reliable model for predicting infliximab (IFX) benefits in bio-naïve Crohn’s disease (CD) is still lacking, we constructed a magnetic resonance enterography (MRE)-based model to predict the risk of loss of response to IFX in bio-naïve patients with CD.

Methods

This retrospective multicenter study enrolled 188 bio-naïve patients with CD who underwent MRE before IFX therapy. Therapeutic outcomes were determined based on clinical symptoms and endoscopic findings within 52 weeks. The areas of bowel wall segmentation were decided by two experienced radiologists in consensus. Texture features were extracted using the least absolute shrinkage and selection operator, and a radiomic model was built using multivariate logistic regression. The model performance was validated by receiver operating characteristic, calibration curve, and decision curve analysis.

Results

The area under the curve of radiomic model was 0.88 (95% confidence interval: 0.82–0.95), and the model provided clinical net benefit in identifying the loss of response to IFX and exhibited remarkable robustness among centers, scanners, and disease characteristics. The high-risk patients defined by the radiomic model were more likely to develop IFX nonresponse than low-risk patients (allp < 0.05).

Conclusions

This novel pretreatment MRE-based model could act as an effective tool for the early estimation of loss of response to IFX in bio-naïve patients with CD.

Key Points

• Magnetic resonance enterography model guides infliximab therapy in Crohn’s disease.

• The model presented significant discrimination and provided net clinical benefit.

• Model divided patients into low- and high-risk groups for infliximab failure.
Single-center, prospective phase 2 trial of high-intensity focused ultrasound (HIFU) in patients with unilateral localized prostate cancer: good functional results but oncologically not as safe as expected
Authors: Duwe Gregor , Boehm Katharina , Haack Maximilian , Sparwasser Peter , Brandt Maximilian Peter , Mager Rene , Tsaur Igor , Haferkamp Axel , Höfner Thomas
Published: March 2023

Purpose

Focal therapy (FT) for localized prostate cancer (PCa) is only recommended within the context of clinical trials by international guidelines. We aimed to investigate oncological follow-up and safety data of focal high-intensity focused ultrasound (HIFU) treatment.

Methods

We conducted a single-center prospective study of 29 patients with PCa treated with (focal) HIFU between 2016 and 2021. Inclusion criteria were unilateral PCa detected by mpMRI-US-fusion prostate biopsy and maximum prostate specific antigen (PSA) of 15 ng/ml. Follow-up included mpMRI-US fusion-re-biopsies 12 and 24 months after HIFU. No re-treatment of HIFU was allowed. The primary endpoint was failure-free survival (FFS), defined as freedom from intervention due to cancer progression.

Results

Median follow-up of all patients was 23 months, median age was 67 years and median preoperative PSA was 6.8 ng/ml. One year after HIFU treatment PCa was still detected in 13/ 29 patients histologically (44.8%). Two years after HIFU another 7/29 patients (24.1%) were diagnosed with PCa. Until now, PCa recurrence was detected in 11/29 patients (37.93%) which represents an FFS rate of 62%.One patient developed local metastatic disease 2 years after focal HIFU. Adverse events (AE) were low with 70% of patients remaining with sufficient erectile function for intercourse and 97% reporting full maintenance of urinary continence.

Conclusion

HIFU treatment in carefully selected patients is feasible. However, HIFU was oncologically not as safe as expected because of progression rates of 37.93% and risk of progression towards metastatic disease. Thus, we stopped usage of HIFU in our department.
Design of experiments and machine learning with application to industrial experiments
Authors: Fontana Roberto , Molena Alberto , Pegoraro Luca , Salmaso Luigi
Published: March 2023

In the context of product innovation, there is an emerging trend to use Machine Learning (ML) models with the support of Design Of Experiments (DOE). The paper aims firstly to review the most suitable designs and ML models to use jointly in an Active Learning (AL) approach; it then reviews ALPERC, a novel AL approach, and proves the validity of this method through a case study on amorphous metallic alloys, where this algorithm is used in combination with a Random Forest model.
Query semantic reconstruction for background in few-shot segmentation
Authors: Guan Haoyan , Spratling Michael
Published: March 2023

Few-shot segmentation (FSS) aims to segment unseen classes using a few annotated samples. Typically, a prototype representing the foreground class is extracted from annotated support image(s) and is matched to features representing each pixel in the query image. However, models learnt in this way are insufficiently discriminatory, and often produce false positives: misclassifying background pixels as foreground. Some FSS methods try to address this issue by using the background in the support image(s) to help identify the background in the query image. However, the backgrounds of these images are often quite distinct, and hence, the support image background information is uninformative. This article proposes a method, QSR, that extracts the background from the query image itself, and as a result is better able to discriminate between foreground and background features in the query image. This is achieved by modifying the training process to associate prototypes with class labels including known classes from the training data and latent classes representing unknown background objects. This class information is then used to extract a background prototype from the query image. To successfully associate prototypes with class labels and extract a background prototype that is capable of predicting a mask for the background regions of the image, the machinery for extracting and using foreground prototypes is induced to become more discriminative between different classes. Experiments achieves state-of-the-art results for both 1-shot and 5-shot FSS on the PASCAL-$$5^{i}$$

5
i

and COCO-$$20^{i}$$

20
i

dataset. As QSR operates only during training, results are produced with no extra computational complexity during testing.
Added value of a regional coupled model: the case study for marine heatwaves in the Caribbean
Authors: Pontoppidan Marie , De Falco Chiara , Mooney Priscilla A. , Nummelin Aleksi , Tjiputra Jerry
Published: March 2023

There is an urgent need to improve capacity to predict marine heatwaves given their substantial negative impacts on marine ecosystems. Here we present the added value of a regional climate simulation, performed with the regional Coupled-Ocean–Atmosphere-Wave-Sediment Transport model COAWST, centered over the Caribbean – one of the first of its kind on a climatological scale. We show its added value with regards to temporal distribution of marine heatwaves, compared with state-of-the-art global models. In this region, global models tend to simulate too few heatwaves that last too long compared to the observation-based dataset of CoralTemp. The regional climate model agrees more favourably with the CoralTemp dataset, particularly in winter. While examining potential mechanisms behind the differences we find that the more realistic representation of marine heatwaves in the regional model arises from the sea surface temperatures ability to increase/decrease more quickly in the regional model than in the global model. The reason for this is two fold. Firstly, the regional model has a shallower mixed layer than the global model which results in a lower heat capacity that allows its sea surface temperatures to warm and cool more quickly. The second reason is found during days when marine heatwaves are increasing in intensity. During these days, reduced wind speeds leads to less latent heat release and a faster warming surface, more so in the regional model than in the global models.
A pilot study of multi-modal pain management for same-day discharge after minimally invasive repair of pectus excavatum (Nuss procedure) in children
Authors: Akinboro Sophia , John Rebecca , Reyna Troy , Davis Rachel , Ayoub Christine , Sangster Rebecca , Kim Joseph , Nguyen Hai , Moreno Claudia , Guner Yigit , Goodman Laura , Yu Peter T. , Morphew Tricia , Kabeer Mustafa
Published: March 2023

Background

Despite advancements in minimally invasive repair of pectus excavatum (MIRPE), Nuss procedure, postoperative pain control remains challenging. This report covers a multimodal regimen using bilateral single-shot paravertebral block (PVB) and bilateral thoracoscopic intercostal nerve (T3–T7) cryoablation, leading to significant reduction in length of stay (LOS) and high rate of same-day discharge.

Methods

This is a comparative study of pain management protocols for patients undergoing the Nuss procedure at a single center from 2016 through 2020. All patients underwent the the same surgical technique for the treatment of pectus excavatum at a single center. Patients received bilateral PVB with continuous infusion (Group 1, n = 12), bilateral PVB with infusion and right-side cryoablation (Group 2, n = 9), or bilateral single-shot PVB and bilateral cryoablation (Group 3, n = 17). The primary outcome was LOS with focus on same-day discharge, and the secondary outcome was decreased opioid usage.

Results

Eleven of 17 patients in Group 3 (65%) (bilateral single-shot PVB and bilateral cryoablation) were discharged the same day as surgery. The remaining Group 3 patients were discharged the following day with no complications or interventions. Compared to Group 1 (no cryoablation), Group 3 had shorter LOS (median 4.4 days vs. 0.7 days, respectively, p < 0.001) and significantly decreased median opioid use on the day of surgery (0.92 mg/kg vs. 0.47 mg/kg, p = 0.006).

Conclusion

Findings demonstrate the feasibility of multimodal pain management for same-day discharge after the Nuss procedure. Future multisite studies are needed to investigate the superiority of this approach to established methods.

Level of Evidence

III.
Inferior vena cava diameter is associated with prognosis in patients with chronic heart failure independent of tricuspid regurgitation velocity
Authors: Iaconelli Antonio , Cuthbert Joe , Kazmi Syed , Maffia Pasquale , Clark Andrew L. , Cleland John G. F. , Pellicori Pierpaolo
Published: March 2023

Aims

A high, Doppler-derived, tricuspid regurgitation velocity (TRV) indicates pulmonary hypertension, which may contribute to right ventricular dysfunction and worsening tricuspid regurgitation leading to systemic venous congestion, reflected by an increase in inferior vena cava (IVC) diameter. We hypothesized that venous congestion rather than pulmonary hypertension would be more strongly associated with prognosis.

Methods and results

895 patients with chronic heart failure (CHF) (median (25th and 75th centile) age 75 (67–81) years, 69% men, LVEF 44 (34–55)% and NT-proBNP 1133 (423–2465) pg/ml) were enrolled. Compared to patients with normal IVC (< 21 mm) and TRV (≤ 2.8 m/s; n = 504, 56%), those with high TRV but normal IVC (n = 85, 9%) were older, more likely to be women and to have LVEF ≥ 50%, whilst those with dilated IVC but normal TRV (n = 142, 16%) had more signs of congestion and higher NT-proBNP. Patients (n = 164, 19%) with both dilated IVC and high TRV had the most signs of congestion and the highest NT-proBNP.

During follow-up of 860 (435–1121) days, 239 patients died. Compared to those with both normal IVC and TRV (reference), patients with high TRV but normal IVC did not have a significantly increased mortality (HR: 1.41; CI: 0.87–2.29; P = 0.16). Risk was higher for patients with a dilated IVC but normal TRV (HR: 2.51; CI: 1.80–3.51; P < 0.001) or both a dilated IVC and elevated TRV (HR: 3.27; CI: 2.40–4.46; P < 0.001).

Conclusion

Amongst ambulatory patients with CHF, a dilated IVC is more closely associated with an adverse prognosis than an elevated TRV.

Graphical Abstract
Characteristics of physician associates/assistants in dermatology
Authors: Griffith Cynthia F. , Young Peter A. , Hooker Roderick S. , Puckett Kasey , Kozikowski Andrzej
Published: March 2023

The dermatology workforce includes physicians, nurse practitioners (NPs), and physician associates/assistants (PAs). The number of dermatologists is growing slowly while the growth of PAs working in dermatology is rapid and accelerating. To understand their characteristics, a descriptive study of PAs practicing in dermatology utilizing the National Commission on Certification of Physician Assistants (NCCPA) workforce dataset on PA practices was undertaken. NCCPA certifies PAs who practice in the United States and queries them about their role, employment, salary, and job satisfaction. Analyses consisted of descriptive statistics, Chi-Square, and Mann–Whitney tests for comparisons between PAs practicing in dermatology versus the total of all other PA specialties. As of 2021, 4,580 certified PAs reported practicing in dermatology—a nearly twofold increase since 2013, when 2323 worked in the specialty. This cohort's median age was 39 years, and 82% were female. Almost all (91.5%) are office based, and 81% work more than 31 h per week. The median salary was $125,000 (2020 dollars). Dermatology PAs work fewer hours and see more patients than their counterparts compared to all 69 PA specialties. At the same time, dermatology PAs are more satisfied and less burnt out when compared to all PAs. The increased number of PAs selecting dermatology as their discipline can help lessen the projected physician shortage in this field.
Fetal NT-proBNP levels and their course in severe anemia during intrauterine treatment
Authors: Siebers Pauline , Gembruch Ulrich , Merz Waltraut Maria , Recker Florian , Müller Andreas , Strizek Brigitte , Geipel Annegret , Berg Christoph , Weber Eva Christin
Published: March 2023

Purpose

In adults and fetuses, N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a marker of cardiac failure and myocardial remodelling. We examined the effect of anemia and intrauterine transfusion (IUT) on NT-proBNP concentrations in fetuses with anemia and established gestational age-dependent reference values of a control group.

Methods

We analyzed NT-proBNP levels in anemic fetuses that underwent serial intrauterine transfusions (IUT), focusing on different causes and severity of anemia and comparing the results to a non-anemic control group.

Results

In the control group, the average NT-proBNP concentration was 1339 ± 639 pg/ml, decreasing significantly with increasing gestational age (R = − 74.04, T = − 3.65, p = 0.001). Subjects had significantly higher NT-proBNP concentrations before initiation of IUT therapy (p < 0.001), showing fetuses with parvovirus B19 (PVB19) infection having the highest concentrations. Hydropic fetuses also showed an increased NT-proBNP concentration compared to non-hydropic fetuses (p < 0.001). During the course of therapy, NT-proBNP concentration before subsequent IUT decreased significantly from pathologically high levels, while MoM-Hb and MoM-MCA-PSV remained pathological.

Conclusion

NT-pro BNP levels in non-anemic fetuses are higher than in postnatal life, decreasing with ongoing pregnancy. Anemia is a hyperdynamic state and its severity correlates with circulating NT-proBNP levels. Highest concentrations occur in fetuses with hydrops and with PVB19 infection, respectively. Treatment by IUT leads to a normalisation of NT-proBNP concentrations, so the measurement of its levels may be useful in therapy monitoring.
Suicide, neuroinflammation and other physiological alterations
Authors: Bengoechea-Fortes Sabina de la Paz , Ramírez-Expósito María Jesús , Martínez-Martos José Manuel
Published: March 2023

Suicide is considered one of the major public health problems worldwide, being the second leading cause of death in the 15–29 age group. It is estimated that every 40s someone in the world commits suicide. The social taboo surrounding this phenomenon as well as the fact that suicide prevention measures currently fail to avoid deaths from this cause, means that more research is needed to understand its mechanisms. The present narrative review on suicide tries to point out several important aspects, such as risk factors or the dynamics of suicide, as well as the current findings in the field of physiology that could offer advances in the understanding of suicide. Subjective measures of risk such as scales and questionnaires are not effective alone, whereas the objective measures can be addressed from physiology. Thus, an increased neuroinflammation in people who take their own lives has been found, with an increase in inflammatory markers such as interleukin-6 and other cytokines in plasma or cerebrospinal fluid. Also, the hyperactivity of the hypothalamic–pituitary–adrenal axis and a decrease in serotonin or in vitamin D levels seems to also be involved. In conclusion, this review could help to understand which factors can trigger an increased risk of dying by suicide, as well as pointing out those alterations that occur in the body when someone attempt to commit suicide or succeeds in taking their own life. There is a need for more multidisciplinary approaches that address suicide to help to raise awareness of the relevance of this problem that causes the death of thousands of people every year.
Multi-objective optimal design of double tuned mass dampers for structural vibration control
Authors: Cao Huong Quoc , Tran Ngoc-An
Published: March 2023

A double tuned mass damper (DTMD) for suppressing oscillations of civil structures is proposed in this study. DTMD is a combination of an undamped TMD and a smaller TMD. The impact of parameters on the essential characteristics, as well as the vibration absorption capacity of DTMD, is investigated. Using genetic algorithms (GA), the optimum parameters of DTMD are determined by minimizing the peak dynamic magnification factor of structural responses for a wide range of excitation frequencies. The effectiveness and robustness of DTMD are also compared with those of the optimized TMD having a similar weight as the DTMD. Furthermore, multi-objective optimization designs of DTMD (for both two-objective and three-objective) are also developed here. This study indicates that the DTMD is more effective than a single TMD. If keeping a similar efficiency to that of an optimized TMD, the optimum DTMD has a broader domain for choosing the frequency and damping ratio. In this sense, a DTMD is much more robust than a single TMD.
Calcineurin-dependent regulation of gap junction conductance and connexin phosphorylation in guinea pig left atrium
Authors: Jabr R. I. , Salvage S. C. , Hatch F. S. , Fry C. H.
Published: March 2023

Atrial fibrillation (AF) occurs from disordered atrial action potential conduction and is associated with reduced gap junction electrical conductance (Gj). The Ca2+ and calmodulin-dependent phosphatase, calcineurin, reduces Gj in ventricular myocardium via a protein phosphatase-1 (PP1)-dependent pathway culminating in phosphorylation of serine368 on connexin43 (pSer368-Cx43). However, characterisation of corresponding pathways in left atrial myocardium, which have a more complex connexin subtype profile, is undefined and was the aim of this study. Gj was measured in guinea-pig left atrium from the frequency-dependent variation of intracellular impedance; intracellular [Ca2+], ([Ca2+]i) in low-Na solution was measured by Fura-2 fluorescence. Phosphorylation of guinea-pig Ser368-Cx43 residues was measured by Western blot; Cx40 was immunoprecipitated and probed for serine/threonine residue phosphorylation. Low-Na solution reversibly reduced Gj, in turn attenuated or prevented by calcineurin inhibitors cyclosporin-A or CAIP, respectively. Moreover, Ser368-Cx43 phosphorylation in low-Na solution was also prevented by CAIP. Changes were partially prevented by fostreicin (FST), a protein phosphatase-2A (PP2A) inhibitor; but not by tautomycin, a PP1 inhibitor. Serine/threonine residues on Cx40 were also phosphorylated in low-Na solution; prevented by CAIP and attenuated by FST. Reduced Gj with raised [Ca2+]i is paralleled by a changed Cx43/Cx40 phosphorylation status; changes mediated by calcineurin and PP2A-dependent pathways, but not PP1. The pharmacological profile underlying changes to guinea-pig atrial gap junction electrical conductance with raised intracellular [Ca2+]i is fundamentally different from that in ventricular myocardium. This provides a targeted drug model whereby atrial and ventricular myocardium can be selectively targeted to correct conduction defects.
Manipulating free will beliefs using online video games
Authors: Tavernier Nel , Wisniewski David , Brass Marcel
Published: March 2023

Research in social psychology and experimental philosophy has investigated lay people’s free will beliefs (FWB). Using different approaches (i.e. experimental manipulations and vignette studies), they investigated how FWB relate to other concepts, and whether changing FWB has an impact on downstream processes such as social behavior. However, both approaches have shortcomings. While experimental manipulations used in social psychology suffer from demand effects, vignettes used in experimental philosophy are often highly abstract. Across two pre-registered studies, we developed a new approach by merging them in an online video game setting. Using this novel, experience-based FWB manipulation, we found that decreasing FWB impacted variables such as perceived control and responsibility in both studies. While the experience-based manipulation influenced participants’ beliefs in free will within the context of the experience (“Within the context of the scenario, would the agent believe in free will?”) in the first study, this manipulation effect did not transfer to participants’ general FWB (“Do you believe in free will?”) in the second study. Overall, our findings suggest a way forward in studying laypeople’s beliefs in free will.
Low diffusion capacity predicts poor prognosis in extensive stage small cell lung cancer: a single-center analysis of 10 years
Authors: Kim Jee Seon , Kim Eun Ji , Jang Jong Geol , Hong Kyung Soo , Ahn June Hong
Published: March 2023

Background

Poor pulmonary function and chronic obstructive pulmonary disease (COPD) are associated with poorer overall survival (OS) in non-small-cell lung cancer (NSCLC) patients. Few studies have investigated the association between pulmonary function and OS in small-cell lung cancer (SCLC) patients. We compared the clinical characteristics of extensive disease SCLC (ED-SCLC) with or without moderately impaired diffusion capacity for carbon monoxide (DLco) and investigated the factors associated with survival in ED-SCLC patients.

Methods

This retrospective single-center study was performed between January 2011 and December 2020. Of the 307 SCLC patients who received cancer therapy during the study, 142 with ED-SCLC were analyzed. The patients were divided into DLco < 60% group and DLco ≥ 60% groups. OS and predictors of poor OS were analyzed.

Results

The median OS of the 142 ED-SCLC patients was 9.3 months and the median age was 68 years. In total, 129 (90.8%) patients had a history of smoking, and 60 (42.3%) had COPD. Thirty-five (24.6%) patients were assigned to the DLco < 60% group. Multivariate analysis revealed that DLco < 60% (odds ratio [OR], 1.609; 95% confidence interval [CI], 1.062–2.437; P = 0.025), number of metastases (OR, 1.488; 95% CI, 1.262–1.756; P < 0.001), and < 4 cycles of first-line chemotherapy (OR, 3.793; 95% CI, 2.530–5.686; P < 0.001) were associated with poor OS. Forty (28.2%) patients received < 4 cycles of first-line chemotherapy; the most common reason for this was death (n = 22, 55%) from grade 4 febrile neutropenia (n = 15), infection (n = 5), or massive hemoptysis (n = 2). The DLco < 60% group had a shorter median OS than the DLco ≥ 60% group (10.6 ± 0.8 vs. 4.9 ± 0.9 months, P = 0.003).

Conclusions

In this study, approximately one quarter of the ED-SCLC patients had DLco < 60%. Low DLco (but not forced expiratory volume in 1 s or forced vital capacity), a large number of metastases, and < 4 cycles of first-line chemotherapy were independent risk factors for poor survival outcomes in patients with ED-SCLC.
CRELD1 variants are associated with bicuspid aortic valve in Turner syndrome
Authors: Pinnaro Catherina T. , Beck Chloe B. , Major Heather J. , Darbro Benjamin W.
Published: March 2023

Turner syndrome (TS) is a chromosomal disorder caused by complete or partial loss of the second sex chromosome and exhibits phenotypic heterogeneity, even after accounting for mosaicism and karyotypic variation. Congenital heart defects (CHD) are found in up to 45 percent of girls with TS and span a phenotypic continuum of obstructive left-sided lesions, with bicuspid aortic valve (BAV) being the most common. Several recent studies have demonstrated a genome-wide impact of X chromosome haploinsufficiency, including global hypomethylation and altered RNA expression. The presence of such broad changes to the TS epigenome and transcriptome led others to hypothesize that X chromosome haploinsufficiency sensitizes the TS genome, and several studies have demonstrated that a second genetic hit can modify disease susceptibility in TS. The objective of this study was to determine whether genetic variants in known heart developmental pathways act synergistically in this setting to increase the risk for CHD, specifically BAV, in TS. We analyzed 208 whole exomes from girls and women with TS and performed gene-based variant enrichment analysis and rare-variant association testing to identify variants associated with BAV in TS. Notably, rare variants in CRELD1 were significantly enriched in individuals with TS who had BAV compared to those with structurally normal hearts. CRELD1 is a protein that functions as a regulator of calcineurin/NFAT signaling, and rare variants in CRELD1 have been associated with both syndromic and non-syndromic CHD. This observation supports the hypothesis that genetic modifiers outside the X chromosome that lie in known heart development pathways may influence CHD risk in TS.
Mediiert die schmerzspezifische Selbstwirksamkeit die Beziehung zwischen Depressivität und arbeitsbezogenen Faktoren bei nichtspezifischen chronischen Rückenschmerzen?
Authors: Hampel Petra , Neumann Anne
Published: March 2023

Hintergrund

Die Chronifizierung nichtspezifischer Rückenschmerzen hängt vor allem mit psychologischen Faktoren zusammen. Wirkmechanismen psychologischer Faktoren wurden jedoch noch wenig bei nichtspezifischen chronischen Rückenschmerzen (CRS) untersucht, insbesondere nicht der Mediatoreffekt der schmerzspezifischen Selbstwirksamkeit.

Fragestellung

Mediiert die schmerzspezifische Selbstwirksamkeit die langfristige Vorhersage arbeitsbezogener Faktoren durch die Depressivität?

Methodik

Im Rahmen einer explorativen Sekundäranalyse wurden einfache Mediationsanalysen zur längsschnittlichen Vorhersage der subjektiven Erwerbsprognose sowie physischen und psychischen Arbeitsfähigkeit durch die Depressivität mit dem Mediator schmerzspezifische Selbstwirksamkeit bei 382 Personen mit nichtspezifischen CRS in der stationären Rehabilitation durchgeführt.

Ergebnisse

Die Befunde sprechen dafür, dass die Depressivität zu Rehabilitationsbeginn die Ausprägungen in allen drei arbeitsbezogenen Kennwerten 24 Monate nach der Rehabilitation vorhersagte und die schmerzspezifische Selbstwirksamkeit 12 Monate nach der Rehabilitation diesen Zusammenhang vermittelte.

Schlussfolgerung

Bei der Behandlung nichtspezifischer CRS sollte zur nachhaltigen Verbesserung des arbeitsbezogenen Rehabilitationserfolgs insbesondere die schmerzspezifische Selbstwirksamkeit, aber auch die Depressivität berücksichtigt werden.
Students feedback analysis model using deep learning-based method and linguistic knowledge for intelligent educational systems
Authors: Abdi Asad , Sedrakyan Gayane , Veldkamp Bernard , van Hillegersberg Jos , van den Berg Stéphanie M.
Published: March 2023

Student feedback analysis is time-consuming and laborious work if it is handled manually. This study explores the use of a new deep learning-based method to design a more accurate automated system for analysing students’ feedback (called DTLP: deep learning and teaching process). The DTLP employs convolutional neural networks (CNNs), bidirectional LSTM (BiLSTM), and attention mechanism.

To the best of our knowledge, a deep learning-based method using a unified feature set, which is representative of word embedding, sentiment knowledge, sentiment shifter rules, linguistic and statistical knowledge, has not been thoroughly studied with regard to sentiment analysis of student feedback. Furthermore, DTLP uses multiple strategies to overcome the following drawbacks: contextual polarity; sentence types; words with similar semantic context but opposite sentiment polarity; word coverage limit of an individual lexicon; and word sense variations. To evaluate the DTLP, we conducted an experiment on a large volume of students’ feedback. The results showed (i) DTLP outperforms the existing systems in the field, (ii) DTLP that learns from this unified feature set can acquire significantly higher performance than one that learns from a feature subset, (iii) the ensemble of sentiment shifter rules, word embedding, statistical, linguistic, and sentiment knowledge allows DTLP to obtain significant performance, and (iv) an attention mechanism into CNN-BiLSTM improves the performance of DTLP. In addition, the deployed method looks for potential causes behind student feedback.
Determinants of autonomous train operation adoption in rail freight: knowledge-based assessment with Delphi-ANP approach
Authors: Djordjević Boban , Fröidh Oskar , Krmac Evelin
Published: March 2023

Railways are the backbone of complex and multimodal transport systems in Europe. To secure a larger share of the transport market and attract existing and future freight customers, further improvement in services is required. To achieve this goal, the use of new technologies in the era of railway automation and digitalization is required. Automatic train operation (ATO) in rail transport is considered a promising solution for providing cost-effective rail products. In this study, we define ATO as autonomous train operation and the feasibility of ATO deployment in rail freight is investigated. For this purpose, a knowledge-based approach is introduced to identify opportunities, problems, and the most appropriate grade of automation in rail freight. In a multi-stage process, Delphi questionnaires were combined with the analytic network process (ANP) method to investigate, define, and weight the determinants for ATO deployment. The final phase of the survey estimated the potential costs and drivers for different grades of automation. The results show that, in addition to the positive impacts of ATO, there are numerous challenges and risks that need to be analysed before ATO is implemented. In addition, the Delphi-ANP approach was used to identify the key determinants for decision-making prior to ATO implementation and the most viable alternative based on them. Investment cost, level of safety, energy saving, and reliability of management system are the most important determinants for the decision to implement ATO. The results of this study can effectively support rail infrastructure managers and operators in strategic planning and decision-making for ATO implementation in rail freight.