bluuebunny/crossref_metadata_2025 huggingface dataset:
Artificial intelligence in BreastScreen Norway: a retrospective analysis of a cancer-enriched sample including 1254 breast cancer cases
Authors: Koch Henrik Wethe , Larsen Marthe , Bartsch Hauke , Kurz Kathinka Dæhli , Hofvind Solveig
Published: March 2023

Objectives

To compare results of selected performance measures in mammographic screening for an artificial intelligence (AI) system versus independent double reading by radiologists.

Methods

In this retrospective study, we analyzed data from 949 screen-detected breast cancers, 305 interval cancers, and 13,646 negative examinations performed in BreastScreen Norway during the period from 2010 to 2018. An AI system scored the examinations from 1 to 10, based on the risk of malignancy. Results from the AI system were compared to screening results after independent double reading. AI score 10 was set as the threshold. The results were stratified by mammographic density.

Results

A total of 92.7% of the screen-detected and 40.0% of the interval cancers had an AI score of 10. Among women with a negative screening outcome, 9.1% had an AI score of 10. For women with the highest breast density, the AI system scored 100% of the screen-detected cancers and 48.6% of the interval cancers with an AI score of 10, which resulted in a sensitivity of 80.9% for women with the highest breast density for the AI system, compared to 62.8% for independent double reading. For women with screen-detected cancers who had prior mammograms available, 41.9% had an AI score of 10 at the prior screening round.

Conclusions

The high proportion of cancers with an AI score of 10 indicates a promising performance of the AI system, particularly for women with dense breasts. Results on prior mammograms with AI score 10 illustrate the potential for earlier detection of breast cancers by using AI in screen-reading.

Key Points

• The AI system scored 93% of the screen-detected cancers and 40% of the interval cancers with AI score 10.

• The AI system scored all screen-detected cancers and almost 50% of interval cancers among women with the highest breast density with AI score 10.

• About 40% of the screen-detected cancers had an AI score of 10 on the prior mammograms, indicating a potential for earlier detection by using AI in screen-reading.
Photodynamische Therapie in Deutschland – Quo vadis?
Authors: Pauleikhoff L. , Rothaus K. , Groß-Bölting F. , Böhringer D. , Lübke J. , Agostini H. , Lange C. ,   Retina.Net CCS Register Studiengruppe
Published: March 2023

Hintergrund

Die photodynamische Therapie (PDT) wurde ursprünglich zur Behandlung der neovaskulären altersabhängigen Makuladegeneration (nAMD) sowie der sekundären chorioidalen Neovaskularisation im Rahmen einer Myopie (mCNV) zugelassen. Zudem wird sie im Rahmen einer Off-label-Therapie bei Patienten mit Aderhauthämangiom, polypoidaler chorioidaler Vaskulopathie (PCV) sowie Chorioretinopathia centralis serosa (CCS) eingesetzt.

Ziel der Arbeit

Das Ziel dieser Arbeit war es, die Entwicklung der PDT-Behandlungszahlen in Deutschland zwischen 2006 und 2021 nachzuzeichnen und die Zusammensetzung der Indikationen für die Behandlung zu untersuchen.

Methoden

In dieser retrospektiven Studie wurden die Qualitätssicherungsberichte der deutschen Krankenhäuser in dem Zeitraum von 2006 bis 2019 ausgewertet und die Anzahl der durchgeführten PDT erfasst. Zudem wurde das Indikationsspektrum für eine PDT exemplarisch an der Klinik für Augenheilkunde des Universitätsklinikums Freiburg und dem Augenzentrum am St. Franziskus Hospital in Münster zwischen 2006 bis 2021 ermittelt. Anhand der geschätzten Prävalenz der CCS und der Chronifizierungsrate wurde schlussendlich die Anzahl der theoretisch behandlungsbedürftigen CCS-Patienten in Deutschland modelliert.

Ergebnisse

Die Anzahl der in Deutschland durchgeführten PDT ist von 1072 Behandlungen im Jahr 2006 auf 202 Behandlungen im Jahr 2019 zurückgegangen. Während die PDT im Jahr 2006 in 86 % der Fälle bei Patienten mit nAMD und in 7 % der Fälle bei mCNV eingesetzt wurde, wurde sie in den Jahren 2016 bis 2021 vornehmlich bei Patienten mit CCS (70 %) und Aderhauthämangiomen (21 %) durchgeführt. Bei einer geschätzten Prävalenz der CCS von 1:10.000 und unter der Annahme, dass 16 % der Fälle eine behandlungsbedürftige chronische CCS (cCCS) entwickeln, müssten in Deutschland ca. 1330 PDT allein für die neu an einer cCCS erkrankten Patienten pro Jahr durchgeführt werden.

Diskussion

Die in Deutschland rückläufige Anzahl an durchgeführten PDT ist v. a. durch eine Umstellung auf die intravitreale Therapie für die nAMD und mCNV zu erklären. Da die PDT aktuell die Therapie der Wahl für die cCCS darstellt, ist von einer Unterversorgung der PDT in Deutschland auszugehen. Es sind zur Gewährleistung einer adäquaten Versorgung der Patienten die robuste Verfügbarkeit von Verteporfin, eine vereinfachte Bewilligungsstruktur seitens der Krankenkassen sowie eine enge Kooperation zwischen niedergelassenen Augenärzten und größeren Zentren notwendig.
Cardiac anomalies in children with congenital duodenal obstruction: a systematic review with meta-analysis
Authors: Pijpers Adinda G. H. , Eeftinck Schattenkerk Laurens D. , de Vries Ralph , Broers Chantal J. M. , Straver Bart , van Heurn Ernest L. W. , Musters Gijsbert D. , Gorter Ramon R. , Derikx Joep P. M.
Published: March 2023

Background

Cardiac anomalies occur frequently in patients with congenital duodenal obstruction (DO). However, the exact occurrence and the type of associated anomalies remain unknown. Therefore, the aim of this systematic review is to aggregate the available literatures on cardiac anomalies in patients with DO.

Methods

In July 2022, a search was performed in PubMed and Embase.com. Studies describing cardiac anomalies in patients with congenital DO were considered eligible. Primary outcome was the pooled percentage of cardiac anomalies in patients with DO. Secondary outcomes were the pooled percentages of the types of cardiac anomalies, type of DO, and trisomy 21. A meta-analysis was performed to pool the reported data.

Results

In total, 99 publications met our eligibility data, representing 6725 patients. The pooled percentage of cardiac anomalies was 29% (95% CI 0.26–0.32). The most common cardiac anomalies were persistent foramen ovale 35% (95% CI 0.20–0.54), ventricular septal defect 33% (95% CI 0.24–0.43), and atrial septal defect 33% (95% CI 0.26–0.41). The most prevalent type of obstruction was type 3 (complete atresias), with a pooled percentage of 54% (95% CI 0.48–0.60). The pooled percentage of Trisomy 21 in patients with DO was 28% (95% CI 0.26–0.31).

Conclusion

This review shows cardiac anomalies are found in one-third of the patients with DO regardless of the presence of trisomy 21. Therefore, we recommend that patients with DO should receive preoperative cardiac screening.

Level of evidence

II.
Wunden durch Vaskulitiden – aktuelle Klassifikation, Diagnostik und Therapie
Authors: Dissemond Joachim
Published: March 2023

Wunden an der Haut können sehr unterschiedliche Ursachen haben. Insbesondere bei klinisch atypischen oder nicht-heilenden Wunden ist die sehr heterogene Gruppe der Vaskulitiden von besonders wichtiger differenzialdiagnostischer Bedeutung. Die Klassifikation der Vaskulitiden erfolgt heute entsprechend den betroffenen Gefäßen nach der Chapel-Hill-Konsensus-Konferenz. Von einer Vaskulitis kann potenziell jeder Teil des Gefäßsystems betroffen sein. Dadurch wird deutlich, dass oft die Gefahr von systemischen Erkrankungen mit hoher interdisziplinärer Relevanz besteht.

Klinisch entwickeln sich die in der Regel sehr schmerzhaften Wunden bei kutaner Vaskulitis aus Nekrosen und sind typischerweise in der floriden Phase von einem erythematös-lividen Randsaum umgeben. In der meist umfangreichen Diagnostik hat zusätzlich zu der klinischen Inspektion die histopathologische Untersuchung von Biopsien einen besonders großen Stellenwert.

Therapeutisch sollte immer eine adäquate Wundtherapie mit dem Fokus auf Schmerzvermeidung und Infektionsprophylaxe durchgeführt werden. Bei begleitenden Ödemen unterstützt die Kompressionstherapie zudem die Wundheilung. Darüber hinaus ist es oft notwendig, systemische Therapien mit immunsuppressiven oder immunmodulierenden Medikamenten einzuleiten. Wann immer möglich, sollten die ursächlich relevanten Faktoren und Komorbiditäten frühzeitig diagnostiziert und vermieden bzw. behandelt werden. Andernfalls besteht die Gefahr von schweren oder sogar tödlichen Krankheitsverläufen.
Subjektives Gefühl digitaler Ausgegrenztheit
Authors: Seifert Alexander
Published: March 2023

Hintergrund

Nicht nur jüngere, sondern zunehmend auch ältere Menschen leben heute in einer Welt, in der digitale Technologien ihren Alltag maßgeblich begleiten. Dennoch nutzen gerade ältere Personen seltener die neuesten Technologien. Fühlen sich ältere Menschen dadurch im Vergleich zu jüngeren Personen besonders ausgeschlossen? Um diese Fragen zu beantworten, wurde anhand einer Bevölkerungsbefragung bei Personen ab 18 Jahren das Empfinden digitaler Exklusion gemessen.

Material und Methoden

Das Datenmaterial stammt aus einer Schweizer Befragung (n = 1604) von Personen im Alter von 18 bis 98 Jahren. Die Datenerhebung erfolgte als standardisierte Onlinebefragung und wurde mit einer optionalen telefonischen Befragung kombiniert.

Ergebnisse

Ein Teil der Personen unter und über 65 Jahren fühlt sich jeweils sozial ausgrenzt, da er nicht immer die aktuellen Alltagstechnologien beherrscht. Innerhalb der Gruppe der 18- bis 64-Jährigen haben 3,6 % ein sehr starkes Exklusionsempfinden, und bei der älteren Gruppe (65 bis 98 Jahre) beträgt dieser Wert 5,5 %, womit ältere Personen eher zur Gruppe der Personen mit sehr starken Gefühlen digitaler Exklusion gehören. Gleichzeitig zeigt die multivariate Zusammenhangsanalyse, dass der Einfluss des Alters durch andere Variablen (Einkommen, Technikeinstellung) nivelliert wird.

Schlussfolgerung

Auch wenn die digitale Transformation voranschreitet, gibt es bei der Techniknutzung weiterhin Ungleichheiten, die sich in Exklusionsgefühlen äußern können. Neben der Frage, welche älteren Personen Technik nutzen oder nicht, sollte in Zukunft die Frage des subjektiven Empfindens der Ausgrenzung stärker berücksichtigt werden.
Unravelling morphoea aetiopathogenesis by next-generation sequencing of paired skin biopsies
Authors: Saracino Amanda M. , Kelberman Daniel , Otto Georg W. , Gagunashvili Andrey , Abraham David J. , Denton Christopher P.
Published: March 2023

Background

Morphoea can have a significant disease burden. Aetiopathogenesis remains poorly understood, with very limited existing genetic studies. Linear morphoea (LM) may follow Blascho’s lines of epidermal development, providing potential pathogenic clues.

Objective

The first objective of this study was to identify the presence of primary somatic epidermal mosaicism in LM. The second objective was tTo explore differential gene expression in morphoea epidermis and dermis to identify potential pathogenic molecular pathways and tissue layer cross-talk.

Methodology

Skin biopsies from paired affected and contralateral unaffected skin were taken from 16 patients with LM. Epidermis and dermis were isolated using a 2-step chemical-physical separation protocol. Whole Genome Sequencing (WGS; n = 4 epidermal) and RNA-seq (n = 5-epidermal, n = 5-dermal) with gene expression analysis via GSEA-MSigDBv6.3 and PANTHER-v14.1 pathway analyses, were performed. RTqPCR and immunohistochemistry were used to replicate key results.

Results

Sixteen participants (93.8% female, mean age 27.7 yrs disease-onset) were included. Epidermal WGS identified no single affected gene or SNV. However, many potential disease-relevant pathogenic variants were present, including ADAMTSL1 and ADAMTS16. A highly proliferative, inflammatory and profibrotic epidermis was seen, with significantly-overexpressed TNFα-via-NFkB, TGFβ, IL6/JAKSTAT and IFN-signaling, apoptosis, p53 and KRAS-responses. Upregulated IFI27 and downregulated LAMA4 potentially represent initiating epidermal ‘damage’ signals and enhanced epidermal-dermal communication. Morphoea dermis exhibited significant profibrotic, B-cell and IFN-signatures, and upregulated morphogenic patterning pathways such as Wnt.

Conclusion

This study supports the absence of somatic epidermal mosaicism in LM, and identifies potential disease-driving epidermal mechanisms, epidermal-dermal interactions and disease-specific dermal differential-gene-expression in morphoea. We propose a potential molecular narrative for morphoea aetiopathogenesis which could help guide future targeted studies and therapies.
A pilot study using unique targeted testing of the urogenital microbiome has potential as a predictive test during IVF for implantation outcome
Authors: Evans Gloria E. , Mahajan Vishakha , Wakeman Sarah , Slatter Tania , Ponnampalam Anna P. , Anderson Trevor P. , Sarwar Makhdoom , Evans John J.
Published: March 2023

Purpose

This pilot study aimed to develop a methodology characterising the urogenital microbiome as a predictive test in the IVF workup.

Methods

Using unique custom qPCRs, we tested for the presence of specific microbial species from vaginal samples and First Catch Urines from the male. The test panel included a range of potential urogenital pathogens, STIs, ‘favourable bacteria’ (Lactobacillus spp.) and ‘unfavourable bacteria’ (anaerobes) reported to influence implantation rates. We tested couples attending Fertility Associates, Christchurch, New Zealand for their first round of IVF.

Results

We found that some microbial species affected implantation. The qPCR result was interpreted qualitatively using the Z proportionality test. Samples from women at the time of Embryo Transfer who did not achieve implantation had significantly higher percent of samples that were positive for Prevotella bivia and Staphylococcus aureus compared to women who did achieve implantation.

Discussion

The results provide evidence that most other microbial species chosen for testing had little functional effect on implantation rates. The addition of further microbial targets (yet to be determined) could be combined in this predictive test for vaginal preparedness on the day of embryo transfer. This methodology has a substantial advantage of being affordable and easily performed in any routine molecular laboratory. This methodology is most suitable as a foundation on which to develop a timely test of microbiome profiling. Using the indicators detected to have a significant influence, these results can be extrapolated.

Conclusion

Using a rapid antigen test, a woman can self-sample prior to embryo transfer and obtain an indication of microbial species present which could influence implantation outcome.
A comparison of special intrauterine balloons and intrauterine contraceptive devices in the treatment of intrauterine adhesions
Authors: Zhuang Lin-Lin , Wang Kai , Shen Hai-Lan , Lin Jia-Hui , Lu Ye , Luo Zhen-Yu , Wang Wen-Rong
Published: March 2023

Purpose

This study aimed to compare the efficacy of a special kind of intrauterine balloon (IUB) and that of an intrauterine contraception device (IUD) for patients with intrauterine adhesions (IUAs) after transcervical resection of adhesion (TCRA).

Methods

In this retrospective cohort study, after TCRA, 31 patients received a special IUB, and 38 patients received an IUD. The Fisher exact test, logistic regression method, Kaplan–Meier method and Cox proportional hazards regression model were used for statistical analysis. A two-sided value of P < 0.05 was considered statistically significant.

Results

The readhesion rate significantly differed between the IUB group and IUD group, at 15.39% and 54.06%, respectively (P = 0.002). For recurrent moderate IUA, patients in the IUB group had lower scores than patients in the IUD group (P = 0.035). There was a significant difference in the intrauterine pregnancy rate of IUA patients in the IUB group and IUD group after treatment, with rates of 55.56% and 14.29%, respectively (P = 0.015).

Conclusion

Patients in the special IUB group had better outcomes than those in the IUD group, which has a certain guiding significance for clinical work.
Third molar eruption in orthopantomograms as a feature for forensic age assessment—a comparison study of different classification systems
Authors: Timme Maximilian , Viktorov Jan , Steffens Laurin , Streeter Adam , Karch André , Schmeling Andreas
Published: March 2023

Evaluation of third molar eruption represents an established method for age assessment of living individuals. Different classification systems are available for the radiological assessment of third molar eruption. The aim of this study was to identify the most accurate and reliable classification system for the mandibular third molar eruption on orthopantomograms (OPG). We compared the method of Olze et al. (2012) with the method of Willmot et al. (2018) and a newly derived classification system using OPGs from 211 individuals aged 15–25 years. The assessments were performed by three experienced examiners. One examiner evaluated all radiographs twice. The correlation between age and stage was investigated and the inter- and intra-rater reliability was estimated for all three methods. Correlation between stage and age was similar between classification systems, although higher in the data from males (Spearman’s rho ranging from 0.568 to 0.583) than from females (0.440 to 0.446). Inter- and intra-rater reliability measures were similar across methods and invariant on sex, with overlapping confidence intervals, although the highest point estimates for both intra- and inter-rater reliability were for the method by Olze et al. with Krippendorf’s alpha values of 0.904 (95% confidence interval 0.854, 0.954) and 0.797 (95% confidence interval 0.744, 0.850). It was concluded that the method of Olze et al. from 2012 is a reliable method for practical application and future studies.
Natalizumab continuation versus switching to ocrelizumab after PML risk stratification in RRMS patients: a natural experiment
Authors: Muñoz-Vendrell Albert , Arroyo-Pereiro Pablo , León Isabel , Bau Laura , Matas Elisabet , Martínez-Yélamos Antonio , Martínez-Yélamos Sergio , Romero-Pinel Lucía
Published: March 2023

Background

Natalizumab (NTZ) and ocrelizumab (OCR) can be used for the treatment of relapsing–remitting multiple sclerosis (RRMS). In patients treated with NTZ, screening for JC virus (JCV) is mandatory, and a positive serology usually requires a change in treatment after 2 years. In this study, JCV serology was used as a natural experiment to pseudo-randomize patients into NTZ continuation or OCR.

Methods

An observational analysis of patients who had received NTZ for at least 2 years and were either changed to OCR or maintained on NTZ, depending on JCV serology status, was performed. A stratification moment (STRm) was established when patients were pseudo-randomized to either arm (NTZ continuation if JCV negativity, or change to OCR if JCV positivity). Primary endpoints include time to first relapse and presence of relapses after STRm and OCR initiation. Secondary endpoints include clinical and radiological outcomes after 1 year.

Results

Of the 67 patients included, 40 continued on NTZ (60%) and 27 were changed to OCR (40%). Baseline characteristics were similar. Time to first relapse was not significantly different. Ten patients in the JCV + OCR arm presented a relapse after STRm (37%), four during the washout period, and 13 patients in the JCV-NTZ arm (32.5%, p = 0.701). No differences in secondary endpoints were detected in the first year after STRm.

Conclusions

The JCV status can be used as a natural experiment to compare treatment arms with a low selection bias. In our study, switching to OCR versus NTZ continuation led to similar disease activity outcomes.
Benefit of intravitreal injections in patients with sub-threshold baseline visual acuity: a retrospective single-centre study
Authors: Grimm Nina-Antonia , Fahimi Sarah , Kück Fabian , Take Patricia , Lauermann Peer , Nguyen-Hoehl Anna , Hoerauf Hans , Feltgen Nicolas , Bemme Sebastian
Published: March 2023

Purpose

To investigate the lower visual acuity threshold for recommending intravitreal injection therapy (IVI). The lower limit of 1.3 logMAR best-corrected visual acuity (BCVA) was adopted in 2006 and has been maintained since then.

Methods

In this retrospective study, data from patients with a logMAR BCVA ≤ 1.3 and 24 months follow-up were analysed. We included patients with neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DME), or retinal vein occlusion (RVO).

Results

The data from 164 patients (nAMD: 107; DME: 15; RVO: 42) were analysed. We observed a significant improvement at all time intervals (0 to 6, 6 to 12, 12 to 18, and 18 to 24 months after initiating IVI) compared to baseline. Across all indications, median BCVA improved from 1.4 to 1.0 within the first 6 months and remained stable within 24 months. Patients received a median of 5 and 10 injections within 6 and 24 months, respectively. Median foveal retinal thickness was 594.5 μm at baseline and dropped to 244.5 μm, 235.5 µm, 183 µm, and 180 µm during the four consecutive time intervals.

Conclusion

Patients with nAMD, DME, and RVO with poor baseline BCVA may also benefit from intravitreal therapy with VEGF-inhibitors. In the present study, we observed functional and morphological improvement over 2 years irrespective of the underlying macular disease. Those patients should not be excluded from therapy.
The angular gyrus serves as an interface between the non-lexical reading network and the semantic system: evidence from dynamic causal modeling
Authors: Junker Frederick Benjamin , Schlaffke Lara , Lange Joachim , Schmidt-Wilcke Tobias
Published: March 2023

Understanding encoded language, such as written words, requires multiple cognitive processes that act in a parallel and interactive fashion. These processes and their interactions, however, are not fully understood. Various conceptual and methodical approaches including computational modeling and neuroimaging have been applied to better understand the neural underpinnings of these complex processes in the human brain. In this study, we tested different predictions of cortical interactions that derived from computational models for reading using dynamic causal modeling. Morse code was used as a model for non-lexical decoding followed by a lexical-decision during a functional magnetic resonance examination. Our results suggest that individual letters are first converted into phonemes within the left supramarginal gyrus, followed by a phoneme assembly to reconstruct word phonology, involving the left inferior frontal cortex. To allow the identification and comprehension of known words, the inferior frontal cortex then interacts with the semantic system via the left angular gyrus. As such, the left angular gyrus is likely to host phonological and semantic representations and serves as a bidirectional interface between the networks involved in language perception and word comprehension.
SARS-CoV-2 transmission in teenagers and young adults in Fútbol Club Barcelona’s Multidisciplinary Sports Training Academy
Authors: Hernández-García María , Bassat Quique , Fumado Victoria , Rodas Gil , Pi Ramon , Miranda-Garcia Maite , Girona-Alarcón Mònica , Català Martí , Alonso Sergio , Alvarez-Lacalle Enrique , López Daniel , Melé-Casas Maria , Pons-Tomas Gemma , F. de Sevilla Mariona , Bonet-Carne Elisenda , Fortuny Claudia , García-Miquel Aleix , Jou Cristina , Adroher Cristina , Claverol Joana , Cubells Marta , Codina Anna , Cuadras Daniel , Gratacós Eduard , Brotons Pedro , Muñoz-Almagro Carmen , Prats Clara , García-García Juan José , Jordan Iolanda
Published: March 2023

Most studies, aimed at determining the incidence and transmission of SARS-CoV-2 in children and teenagers, have been developed in school settings. Our study conducted surveillance and inferred attack rates focusing on the practice of sports. Prospective and observational study of those attending the sports facilities of Fútbol Club Barcelona (FCB), in Barcelona, Spain, throughout the 2020–2021 season. Participants were young players (from five different sports) and adult workers, who belonged to stable teams (shared routines and were involved in same quarantine rules). Biweekly health questionnaires and SARS-CoV-2 screening were conducted. From the 234 participants included, 70 (30%) both lived and trained in the FCB facilities (Recruitment Pathway 1;RP1) and 164 (70%) lived at their own household and just came to the facilities to train (RP2). During the study, 38 positive cases were identified; none had severe symptoms or needed hospitalization. The overall weekly incidence in the cohorts did not differ compared to the one expected in the community, except for 2 weeks when an outbreak occurred. The attack rate (AR) was three times higher for the participants from RP1, in comparison to those from RP2 (p < 0.01). A Basketball team showed a significant higher AR.

  Conclusion: Physical activities in stable teams are not related to an increased risk of transmission of SARS-CoV-2, since there were the same observed cases than expected in the community. The risk is higher in indoor sports (Basketball vs. Football), and in closed cohort living settings (RP1 vs. RP2). The fulfilment of preventive measures is essential.

What is Known:• Despite the low numerical impact caused in paediatric hospitalizations during COVID-19 pandemic, the social impact has been maximum.• The transmission potential in children and teenagers is limited, and it had been widely demonstrated in school settings.

What is New:• Group physical activities in children and teenagers are not also related to an increased risk of transmission of SARS-CoV-2, when preventive measures, such as washing hands, and screening protocols are applied.• Routine and semi-professional sports activities seem safe environments to promote during this pandemic.
Younger postnatal age is associated with a lower heart rate on Holter monitoring during the first week of life
Authors: Uusitalo Asta , Tikkakoski Antti , Lehtinen Pieta , Ylänen Kaisa , Korhonen Päivi H. , Poutanen Tuija
Published: March 2023

To evaluate heart rate (HR), the presence of extrasystoles and other Holter findings among healthy newborns, and to collect data for new normal limits for Holter parameters in newborns. For this cross-sectional study, 70 healthy term newborns were recruited to undergo 24-h Holter monitoring. Linear regression analysis was used in HR analyses. The age-specific limits for HRs were calculated using linear regression analysis coefficients and residuals. The mean (SD) age of the infants was 6.4 (1.7) days during the recording. Each consecutive day of age raised the minimum and mean HR by 3.8 beats per minute (bpm) (95% CI: 2.4, 5.2; P < .001) and 4.0 bpm (95% CI: 2.8, 5.2; P < .001), respectively. Age did not correlate with maximum HR. The lowest calculated limit for minimum HR ranged from 56 bpm (aged 3 days) to 78 bpm (aged 9 days). A small number of atrial extrasystoles and ventricular extrasystoles were observed in 54 (77%) and 28 (40%) recordings, respectively. Short supraventricular or ventricular tachycardias were found in 6 newborns (9%).

Conclusion: The present study shows an increase of 20 bpm in both the minimum and mean HRs of healthy term newborns between the 3rd and 9th days of life. Daily reference values for HR could be adopted in the interpretation of HR monitoring results in newborns. A small number of extrasystoles are common in healthy newborns, and isolated short tachycardias may be normal in this age group.

What is Known:

• The current definition of bradycardia in newborns is 80 beats per minute.

• This definition does not fit into the modern clinical setting of continuously monitored newborns, where benign bradycardias are commonly observed.

What is New:

• A linear and clinically significant increase in heart rate was observed in infants between the ages of 3 and 9 days.

• It appears as though lower normal limits for heart rate could be applied to the youngest newborns.
Heat shock protein 90 (HSP90) inhibitors in gastrointestinal cancer: where do we currently stand?—A systematic review
Authors: Magyar Christian Tibor Josef , Vashist Yogesh K. , Stroka Deborah , Kim-Fuchs Corina , Berger Martin D. , Banz Vanessa M.
Published: March 2023

Purpose

Dysregulated expression of heat shock proteins (HSP) plays a fundamental role in tumor development and progression. Consequently, HSP90 may be an effective tumor target in oncology, including the treatment of gastrointestinal cancers.

Methods

We carried out a systematic review of data extracted from clinicaltrials.gov and pubmed.gov, which included all studies available until January 1st, 2022. The published data was evaluated using primary and secondary endpoints, particularly with focus on overall survival, progression-free survival, and rate of stable disease.

Results

Twenty trials used HSP90 inhibitors in GI cancers, ranging from phase I to III clinical trials. Most studies assessed HSP90 inhibitors as a second line treatment. Seventeen of the 20 studies were performed prior to 2015 and only few studies have results pending. Several studies were terminated prematurely, due to insufficient efficacy or toxicity. Thus far, the data suggests that HSP90 inhibitor NVP-AUY922 might improve outcome for colorectal cancer and gastrointestinal stromal tumors.

Conclusion

It currently remains unclear which subgroup of patients might benefit from HSP90 inhibitors and at what time point these inhibitors may be beneficial. There are only few new or ongoing studies initiated during the last decade.
The evolving volcano-ice interactions of Crater Glacier, Mount St. Helens, Washington (USA)
Authors: Sobolewski Linda , Hansteen Thor H. , Zorn Edgar U. , Stenner Christian , Florea Lee J. , Burgess Sarah A. , Ionescu Artur , Cartaya Eduardo , Pflitsch Andreas
Published: March 2023

Interactions between volcanoes and glaciers provide insight to the evolution of a volcanic edifice and may be an indicator for renewed volcanic activity. At Mount St. Helens, Crater Glacier, which has formed in the volcanic crater after the eruption in 1980, is one of the world’s last expanding glaciers and provides a unique opportunity to characterize the evolution of a glacier expanding onto an area of significant thermal flux. We combine photographic documentation and glaciovolcanic cave surveys with remote sensing data from Google Earth, UAS, and LiDAR to analyze the present state of Crater Glacier and reconstruct its development since the emplacement of the 2004–2008 lava dome. Our results show that snow accumulation has caused Crater Glacier to grow from 2009 to 2019 by approximately 13.8 × 106 m3, during which time the glacier toe advanced by several hundred meters. The glacier-dome interface shift toward higher elevations against the 2004–2008 lava dome and subsequent encroachment onto thermally active areas led to glacier modification via extensive subglacial cave system formation. Analysis of subglacial tephra layers revealed the existence of juvenile material from the 2004–2008 eruption cycle, providing insights about glacier subsidence of ~ 40 m since 2004/2005 in spite of net growth. Although the lava dome is cooling, the glacier-dome interface seems to have become increasingly stable in the past few years. Our results suggest that glacier development in the accumulation area adjacent to the dome is now being affected by the thermal characteristics of the lava dome itself, making monitoring internal glacier development via tracking glaciovolcanic cave expansion a potentially important volcano monitoring tool.
Induced Disjoint Paths and Connected Subgraphs for H-Free Graphs
Authors: Martin Barnaby , Paulusma Daniël , Smith Siani , van Leeuwen Erik Jan
Published: March 2023

Paths $$P^1,\ldots ,P^k$$

P
1

,
…
,

P
k

in a graph $$G=(V,E)$$

G
=
(
V
,
E
)

are mutually induced if any two distinct $$P^i$$

P
i

and $$P^j$$

P
j

have neither common vertices nor adjacent vertices. The Induced Disjoint Paths problem is to decide if a graph G with k pairs of specified vertices $$(s_i,t_i)$$

(

s
i

,

t
i

)

contains k mutually induced paths $$P^i$$

P
i

such that each $$P^i$$

P
i

starts from $$s_i$$

s
i

and ends at $$t_i$$

t
i

. This is a classical graph problem that is -complete even for $$k=2$$

k
=
2

. We introduce a natural generalization, Induced Disjoint Connected Subgraphs: instead of connecting pairs of terminals, we must connect sets of terminals. We give almost-complete dichotomies of the computational complexity of both problems for H-free graphs, that is, graphs that do not contain some fixed graph H as an induced subgraph. Finally, we give a complete classification of the complexity of the second problem if the number k of terminal sets is fixed, that is, not part of the input.
Discrete Yamabe Problem for Polyhedral Surfaces
Authors: Dal Poz Kouřimská Hana
Published: March 2023

We study a new discretization of the Gaussian curvature for polyhedral surfaces. This discrete Gaussian curvature is defined on each conical singularity of a polyhedral surface as the quotient of the angle defect and the area of the Voronoi cell corresponding to the singularity. We divide polyhedral surfaces into discrete conformal classes using a generalization of discrete conformal equivalence pioneered by Feng Luo. We subsequently show that, in every discrete conformal class, there exists a polyhedral surface with constant discrete Gaussian curvature. We also provide explicit examples to demonstrate that this surface is in general not unique.
Clinical application of machine learning and computer vision to indocyanine green quantification for dynamic intraoperative tissue characterisation: how to do it
Authors: Hardy Niall P. , MacAonghusa Pol , Dalli Jeffrey , Gallagher Gareth , Epperlein Jonathan P. , Shields Conor , Mulsow Jurgen , Rogers Ailín C. , Brannigan Ann E. , Conneely John B. , Neary Peter M. , Cahill Ronan A.
Published: March 2023

Introduction

Indocyanine green (ICG) quantification and assessment by machine learning (ML) could discriminate tissue types through perfusion characterisation, including delineation of malignancy. Here, we detail the important challenges overcome before effective clinical validation of such capability in a prospective patient series of quantitative fluorescence angiograms regarding primary and secondary colorectal neoplasia.

Methods

ICG perfusion videos from 50 patients (37 with benign (13) and malignant (24) rectal tumours and 13 with colorectal liver metastases) of between 2- and 15-min duration following intravenously administered ICG were formally studied (clinicaltrials.gov: NCT04220242). Video quality with respect to interpretative ML reliability was studied observing practical, technical and technological aspects of fluorescence signal acquisition. Investigated parameters included ICG dosing and administration, distance–intensity fluorescent signal variation, tissue and camera movement (including real-time camera tracking) as well as sampling issues with user-selected digital tissue biopsy. Attenuating strategies for the identified problems were developed, applied and evaluated. ML methods to classify extracted data, including datasets with interrupted time-series lengths with inference simulated data were also evaluated.

Results

Definable, remediable challenges arose across both rectal and liver cohorts. Varying ICG dose by tissue type was identified as an important feature of real-time fluorescence quantification. Multi-region sampling within a lesion mitigated representation issues whilst distance–intensity relationships, as well as movement-instability issues, were demonstrated and ameliorated with post-processing techniques including normalisation and smoothing of extracted time–fluorescence curves. ML methods (automated feature extraction and classification) enabled ML algorithms glean excellent pathological categorisation results (AUC-ROC > 0.9, 37 rectal lesions) with imputation proving a robust method of compensation for interrupted time-series data with duration discrepancies.

Conclusion

Purposeful clinical and data-processing protocols enable powerful pathological characterisation with existing clinical systems. Video analysis as shown can inform iterative and definitive clinical validation studies on how to close the translation gap between research applications and real-world, real-time clinical utility.
Functional seed traits as predictors of germination and seedling growth for species with potential for restoration in Caquetá, Colombia
Authors: Guzmán María N. Nieto , Beltrán Luis C. , Rodriguez Carlos H. , Roa-Fuentes Lilia L.
Published: March 2023

Key message

Pre-germination requirements are not accurately predicted by seed traits of size and mass. However, small-seeded species show high germination and slow early seedling growth rates.

Deforestation in the tropics is one of the greatest biodiversity crises of the Anthropocene. In response, tropical countries such as Colombia have committed to restoring degraded lands and reconnecting forest fragments. To contribute to this mission, we evaluated how easy-to-measure seed functional traits predicted germination requirements and early seedling growth rates (RGRs) for 11 tree species native to the Andean-Amazon piedmont region. Pre-sowing treatments followed a 3 × 3 factorial design: three light conditions (full, partial, and no light) and three pre-germination treatments (hot water, abrasion, and control). A cluster analysis grouped species into three groups driven chiefly by highly correlated variables of seed size and mass. However, species within and among functional groups differed in their response to pre-germination treatments. One exception includes the small-seeded species group responding with little-to-no germination to the absence of light. Since functional traits were highly correlated, we used Principal Component Regression (PCR) to predict germination metrics (germination percentage, velocity, and vigor) and RGRs. The multivariate trait axis of seed size and seed mass measurements (PC1) correlated negatively with germination metrics and positively with RGRs. Our results highlight the challenges associated with using easy-to-measure functional traits to deduce the most effective pre-sowing treatment. Other more relevant functional traits can be measured in lab, but a shotgun approach to testing pre-germination treatments may be more cost-effective. High germination in small-sized seed species highlights the early-successional niche these species occupy, but reduced RGR may represent a tradeoff associated with having relatively few resources stored in seed.
Beiträge kommunaler Planung für mehr Ernährungssicherheit in deutschen Städten
Authors: Augustin Hanna , Rosol Marit
Published: March 2023

Zur Einzelhandelssteuerung entwickeln viele deutsche Kommunen Einzelhandelskonzepte. Eine Bestandsaufnahme der Lebensmittelversorgung gehört dabei inzwischen zu den Standardinstrumenten. Gemeinhin wird dabei ein distanzbasierter Indikator verwendet, der den Grad der Versorgung anhand von Luftliniendistanzen, z. T. auch realen Wegedistanzen zwischen Wohn- und nächstem Einkaufsort misst. Der Zugang zu Lebensmitteln wird jedoch über diese Distanz hinaus von weiteren physisch-räumlichen und sozioökonomischen Faktoren beeinflusst. Diese werden bislang kaum berücksichtigt. Ein unzureichender Zugang zu Lebensmitteln ist nicht nur aus gesundheitlicher Perspektive problematisch, sondern v. a. auch aufgrund der sozialen Funktion von Ernährung als wichtigem Feld gesellschaftlicher Teilhabe. Der erschwerte Zugang zu Lebensmitteln trifft insbesondere Menschen in prekären Lebenslagen, die ohnehin bereits in ihrer gesellschaftlichen Teilhabe eingeschränkt sind. In diesem Artikel stellen wir deshalb ein Modell vor, welches theoretisch fundiert die physisch-räumliche und sozioökonomische Einbettung des Lebensmittelzugangs umfassend und systematisch erfasst. Anhand ausgewählter Ergebnisse einer Studie, die mit eben diesem Ansatz in Bremen durchgeführt wurde, zeigen wir, von welchen Zugangsbarrieren Bewohner*innen zweier als gut versorgt geltender Stadtteile betroffen sind. Das vorrangige Ziel dieses Aufsatzes ist es, stärker für die komplexe Problematik des Lebensmittelzugangs zu sensibilisieren. Zudem benennen wir abschließend Handlungsansätze, mit der die Einzelhandelssteuerung und andere kommunale Initiativen den Zugang zu Lebensmitteln verbessern können.
Is procalcitonin a reliable indicator of sepsis in spinal cord injury patients: an observational cohort study
Authors: Anas Mohammad , Hasan Tayyab , Raja Usman , Raza Wajid A.
Published: March 2023

Study Design

Prospective observational cohort study.

Objective

To understand if serum procalcitonin (PCT) is a reliable indicator of sepsis in spinal cord injury (SCI) patients for better prognosis and earlier diagnosis when compared with other common biomarkers such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cells (WBC), blood culture and body temperature.

Methods

From March 2021 to August 2022, data were collected for SCI patients who developed septicaemia. In addition to neurology and admission, the following blood samples were collected on day one of infection: PCT, CRP and WBC. Linear regression analysis was performed to determine the relationship between PCT, CRP and WBC.

Results

A total of 27 SCI patients had an infection during their stay in the regional centre; however, only 10 developed septicaemias. 100% of SCI individuals with sepsis had elevated PCT levels, whilst 60% had elevated CRP and 30% had elevated WBC levels. There was a strong positive correlation between PCT and CRP (R2 = 0.673, CI = 95%, 5.5–22.8, p < 0.05) and a weaker positive correlation between PCT and WBC (R2 = 0.110, CI = 95%, 4.2–10.9, p < 0.05).

Conclusion

In SCI individuals, there was a correlation between serum PCT levels and septicaemia. Alongside this, PCT appeared to be more consistent throughout the study population when compared with CRP and WBC. However, this was a preliminary study and further research is required on a larger scale.
Sinc integrals revisited
Authors: Abel Ulrich , Kushnirevych Vitaliy
Published: March 2023

The purpose of this paper is the evaluation of the Fourier transform of powers of the sinc function multiplied by monomials, also in the cases when log terms arise. Such evaluations appear only rarely in the literature. Some old sources are hardly available. Because of notations not in use today, several original works are difficult to read. We apply an approach by J. H. Michell in a variant of G. H. Hardy to integrals over sinc powers and their Fourier transforms. Moreover, the connection of such integrals with B‑splines is accentuated.
Efficient controlled release of cannabinoids loaded in γ-CD-MOFs and DPPC liposomes as novel delivery systems in oral health
Authors: Rodríguez-Martínez Jorge , Sánchez-Martín María-Jesús , Valiente Manuel
Published: March 2023

Olivetol (OLV), as a cannabidiol (CBD) analog, was incorporated in γ-cyclodextrin metal-organic frameworks (γ-CD-MOFs) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes as potential analgesic drug delivery systems (DDS) for dental hypersensitivity (DH) treatment. These DDS have been scarcely employed in oral health, being the first time in case of MOFs loaded with cannabinoids. In vitro experiments using bovine teeth were performed to verify if the drug is able to reach the dentin, where it can flow to the pulp tissues and exert its analgesic effect; enamel and dentin regions were analyzed by synchrotron radiation-based FTIR microspectroscopy. Principal component analysis (PCA) was used to process the spectroscopic data as a powerful chemometric tool, and it revealed a similar behavior in both regions. The studied DDS have been characterized by different techniques, and is was demonstrated that DDS is an efficient way to carry the drug through dental tissues without compromising their structure.

Graphical Abstract
Architecting decentralized control in large-scale self-adaptive systems
Authors: Andersson Jesper , Caporuscio Mauro , D’Angelo Mirko , Napolitano Annalisa
Published: March 2023

Architecting a self-adaptive system with decentralized control is challenging. Indeed, architects shall consider several different and interdependent design dimensions and devise multiple control loops to coordinate and timely perform the correct adaptations. To support this task, we propose Decor, a reasoning framework for architecting and evaluating decentralized control. Decor provides (i) multi-paradigm modeling support, (ii) a modeling environment for MAPE-K style decentralized control, and (iii) a co-simulation environment for simulating the decentralized control together with the managed system and estimating the quality attributes of interest. We apply the Decor in three case studies: an intelligent transportation system, a smart power grid, and a cloud computing application. The studies demonstrate the framework’s capabilities to support informed architectural decisions on decentralized control and adaptation strategies.
Glycine protects against doxorubicin-induced heart toxicity in mice
Authors: Shosha Mayada I. , El-Ablack Fawzia Z. , Saad Entsar A.
Published: March 2023

Doxorubicin (DOXO) is a well-known cancer chemotherapeutic. However, its toxic effect on the heart limits its clinical application. This study aimed to assess the effectiveness of glycine administration to counteract the DOXO-induction of cardiomyopathy in mice. Fifty male albino mice were divided into five groups (n = 10/group) as follows: control, DOXO, Gp100, Gp150, and Gp200. Histopathological examination of the heart, and biochemical examinations for heart function (creatine phosphokinase (CPK), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST)), inflammation (tumor necrosis factor-alpha (TNF-α) and interleukin 10 (IL-10)), oxidative stress (malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase, nitric oxide (NO), and uric acid), kidney function (urea and creatinine), and minerals (calcium, phosphorus, sodium, and potassium) were carried out. Cardiomyopathy induced by DOXO treatment (15 mg/kg total dose) was ascertained via pathological alterations seen in heart tissue and verified biochemically via increases (P < 0.001) in CPK, LDH, AST, TNF-α, IL-10, MDA, NO, Na, and K levels along with decreases (P < 0.001) in GSH, SOD, catalase, and uric acid. Glycine co-treatment, using doses of 100, 150, and 200 mg/kg, in a dose-dependent manner, displayed ameliorated heart architecture, significantly (P < 0.001) improved biochemical heart function tests, reduced oxidative stress and inflammation, and controlled mineral levels. The positive actions of glycine in DOXO-induced cardiotoxicity amelioration via modulating oxidative stress, inflammation, and immunity are confirmed. Glycine antioxidative properties may be behind its positive outcomes. Finally, we present glycine as a worthy possible option against DOXO-induced heart damage after more validation.