bluuebunny/crossref_metadata_2025 huggingface dataset:
Coordination on networks with farsighted and myopic agents
Authors: Mauleon Ana , Schopohl Simon , Taalaibekova Akylai , Vannetelbosch Vincent
Published: January 2022

We study a coordination game on a fixed connected network where players have to choose between two projects. Some players are moderate (i.e. they are ex-ante indifferent between both projects) while others are stubborn (i.e. they always choose the same project). Benefits for moderate players are increasing in the number of neighbors who choose the same project. In addition, players are either farsighted or myopic. Farsighted players anticipate the reactions of others while myopic players do not. We show that, when all players are farsighted, full coordination among the moderate players is reached except if there are stubborn players for both projects. When the population is mixed, the set of stable strategy profiles is a refinement of the set of Nash equilibrium strategy profiles. In fact, turning myopic players into farsighted ones eliminates gradually the inefficient Nash equilibria. Finally, we consider a social planner who can improve coordination by means of two policy instruments: adding links to the network (socialization) and/or turning myopic players into farsighted ones (education).
Penicillinase plasmid Australia type in Neisseria gonorrhoeae isolated in Poland
Authors: Walter de Walthoffen Szymon
Published: January 2022

Purpose

Neisseria gonorrhoeae is an etiological agent of gonorrhea which remains a major public health problem the mechanisms that determine resistance to drugs of the beta-lactam class, which are recommended for the treatment of gonorrhea, are currently the most important problem in its treatment. Chromosomal mutations are responsible for resistance to ceftriaxone and cefepime. The possibility of mutations in the gene encoding beta-lactamase (blaTEM) in the penicillinase plasmid may also turn out to be a serious threat.

Methods

The occurrence of resistance encoded on penicillinase plasmid has been investigated. For this purpose, the susceptibility of bacteria was determined and the gene for resistance to beta-lactams as well as the plasmids themselves was typed.

Results

Of the 333 strains tested, 21 (6.3%) had the beta-lactamase gene and produced penicillinase. Two of the beta-lactamase: TEM-1 and TEM-135 occurred among the tested strains of N. gonorrhoeae. Most of the known penicillinase plasmid types of N. gonorrhoeae were demonstrated: the Asian, the African, the Toronto/Rio plasmids and Australian variants.

Conclusions

In the first 3 years, TEM-1 beta-lactamases dominated in N. gonorrhoeae, which were replaced by TEM-135 in the following years of the study. Not all molecular methods are capable of varying the types of penicillinase plasmids. A particularly noteworthy observation is the fact that the Australia-type of penicillinase plasmid (3270 bp) was identified for the first time in Europe, and the second time in the world.
Fourier spotting: a novel setup for single-color reflectometry
Authors: Siegel Johannes , Berner Marcel , Werner Juergen H. , Proll Guenther , Fechner Peter , Schubert Markus
Published: January 2022

Single-color reflectrometry is a sensitive and robust detection method in optical biosensor applications, for example for bioanalysis. It is based on the interference of reflected monochromatic radiation and is label free. We present a novel setup for single-color reflectometry based on the patented technology of Berner et al. from 2016. Tilting areas of micro-mirrors allow us to encode the optical reflection signal of an analyte and reference channel into a particular carrier frequency with the amplitude being proportional to the local reflection. Therefore, a single photodiode is sufficient to collect the signals from both channels simultaneously. A 180∘ phase shift in the tilt frequency of two calibrated micro-mirror areas leads to a superposition of the analyte and reference signal which enables an efficient reduction of the baseline offset and potential baseline offset drift. A performance test reveals that we are able to detect changes of the refractive index n down to Δn < 0.01 of saline solutions as regents. A further test validates the detection of heterogeneous binding interaction. This test compromises immobilized testosterone-bovine serum albumin on a three-dimensional layer of biopolymer as ligand and monoclonal anti-testosterone antibodies as analyte. Antibody/antigen binding induces a local growth of the biolayer and change in the refractive index, which is measured via the local change of the reflection. Reproducible measurements enable for the analysis of the binding kinetics by determining the affinity constant KA = 1.59 × 10− 7 M− 1. In summary, this work shows that the concept of differential Fourier spotting as novel setup for single-color reflectometry is suitable for reliable bioanalysis.
Breast Reconstruction–Prospective Follow up on Breast Cancer Patients’ Health‐Related Quality of Life
Authors: Rautalin Mervi , Jahkola Tiina , Roine Risto P.
Published: January 2022

Background

Analysing the results of breast reconstruction is important both in terms of oncological safety and health‐related quality of life (HRQoL). Immediate breast reconstruction (IBR) is thought to be prone to complications and heavy for patients with no time to adapt to having cancer. Delayed reconstruction (DR) is an option after primary surgery and oncological treatments, but requires patients to go through two recovery periods after surgery.

Methods

A prospective study of 1065 breast cancer patients with repeated measurement of HRQoL with both generic (15D) and disease specific (EORTC QLQ C‐30 BR23) measuring tools included 51 IBR patients and 41 DR patients. These patients’ HRQoL and reconstruction methods were studied in more detail alongside with clinical data to determine HRQoL levels for patients with IBR and those with mastectomy and DR during a 24‐month follow‐up. Measuring points were baseline, 3, 6, 12 and 24 months.

Results

Most frequent techniques used were abdominal flaps (IBR n = 16, DR n = 14), latissimus dorsi flaps (LD) (IBR n = 19, DR n = 10), implants (IBR n = 12) and fat grafting (DR n = 6). Smaller groups were excluded from group comparisons. Approximately one third of the patients encountered complications. Symptom scores did not differ between reconstruction methods. DR patients had better overall HRQoL at 12 months, but at 24 months the situation had changed in favour of IBR. Both approaches of reconstructive surgery produced good HRQoL with no significant differences between the approaches studied.
Anlotinib combined with temozolomide suppresses glioblastoma growth via mediation of JAK2/STAT3 signaling pathway
Authors: Xu Peng , Wang Handong , Pan Hao , Chen Jiakai , Deng Chulei
Published: January 2022

Purpose

Anlotinib protects against carcinogenesis through the induction of autophagy and apoptosis. The current study evaluated the role and molecular mechanisms of anlotinib in glioblastoma, and the effects of anlotinib in combination with temozolomide (TMZ).

Methods

Cell Counting Kit-8 and colony-forming assays were used to evaluate cell viability. Cell migration and invasion were assessed by wound-healing, Transwell migration, and Matrigel invasion assays. Cellular apoptosis and cell cycle analysis were determined by flow cytometry. Angiogenesis was assessed using human umbilical vein endothelial cells (HUVECs). Vascular endothelial growth factor A (VEGFA) was measured by enzyme-linked immunosorbent assay. Protein expression was determined by western blotting or immunofluorescence staining. The in vivo anti-glioblastoma effect was assessed with live imaging of tumor xenografts in nude mice.

Results

Anlotinib restricted the proliferation, migration, and invasion of glioblastoma cells in a dose-dependent manner. Tumor supernatant from glioblastoma cells treated with anlotinib inhibited angiogenesis in HUVECs. Anlotinib induced autophagy in glioblastoma cells by increasing Beclin-1 and microtubule-associated protein 1 light chain 3B (LC3B) levels. Mechanistically, anlotinib inhibited the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3)/VEGFA signaling pathway. STAT3 inhibition by S3I-201 decreased VEGFA and suppressed cellular proliferation and movement. TMZ enhanced the anti-glioblastoma ability of anlotinib. Finally, anlotinib inhibited tumor growth and JAK2/STAT3/VEGFA signaling in xenografts.

Conclusion

Anlotinib exerts anti-glioblastoma activity possibly through the JAK2/STAT3/VEGFA signaling pathway. TMZ potentiated the anti-glioblastoma effect of anlotinib via the same signaling pathway, indicating the potential application of anlotinib as a treatment option for glioblastoma.
Use of the Behavioral Regulation in Exercise Questionnaire-2 to assess motivation for physical activity in persons with rheumatoid arthritis: an observational study
Authors: Videm Vibeke , Hoff Mari , Liff Marthe Halsan
Published: January 2022

Arthritis patients may show little motivation for physical activity (PA), resulting in a sedentary lifestyle. The primary objective of the study was to investigate whether motivation for PA and fulfillment of PA recommendations were associated with cardiorespiratory fitness in patients with RA. The exploratory objective was to study whether university students could be used as controls for RA patients in future studies of PA motivation. Peak oxygen uptake (VO2peak) was measured in 93 RA patients. The patients and 354 students filled in the Behavioral Regulation in Exercise Questionnaire-2 (BREQ-2). Data were analyzed using structural equation modeling with adjustment for age and sex. The BREQ-2 scores were also compiled to an overall motivational style “Relative Autonomy Index” as previously published. Mean VO2peak for the RA patients was 32.2 (SD: 9.6) mL × min−1 × kg−1. Only 29 patients (31%) fulfilled the current recommendations for PA. BREQ-2 scores were associated with measured VO2peak (standardized coefficient 0.33, p < 0.001). Whether a person fulfilled the current recommendations for PA was a significant mediator of this effect (standardized coefficients: mediated effect; 0.22, p = 0.001, remaining direct effect; 0.11, p = 0.18). The Relative Autonomy Index also significantly predicted measured VO2peak (standardized coefficient 0.30, p < 0.001). The underlying BREQ-2 factor structure was significantly different between RA patients and university students, and comparison of scores would not be adequate. Motivation for PA was significantly associated with measured VO2peak in RA patients. The effect was mediated by whether the patient fulfilled the current recommendations for PA. Addressing and stimulating motivation is important when intervening to increase PA and cardiovascular fitness in RA patients.
Magnetic maps in animal navigation
Authors: Lohmann Kenneth J. , Goforth Kayla M. , Mackiewicz Alayna G. , Lim Dana S. , Lohmann Catherine M. F.
Published: January 2022

In addition to providing animals with a source of directional or ‘compass’ information, Earth’s magnetic field also provides a potential source of positional or ‘map’ information that animals might exploit to assess location. In less than a generation, the idea that animals use Earth’s magnetic field as a kind of map has gone from a contentious hypothesis to a well-established tenet of animal navigation. Diverse animals ranging from lobsters to birds are now known to use magnetic positional information for a variety of purposes, including staying on track along migratory pathways, adjusting food intake at appropriate points in a migration, remaining within a suitable oceanic region, and navigating toward specific goals. Recent findings also indicate that sea turtles, salmon, and at least some birds imprint on the magnetic field of their natal area when young and use this information to facilitate return as adults, a process that may underlie long-distance natal homing (a.k.a. natal philopatry) in many species. Despite recent progress, much remains to be learned about the organization of magnetic maps, how they develop, and how animals use them in navigation.
Seasonal Cumulative Effect of Ural Blocking Episodes on the Frequent Cold events in China during the Early Winter of 2020/21
Authors: Yao Yao , Zhang Wenqi , Luo Dehai , Zhong Linhao , Pei Lin
Published: January 2022

Starting in mid-November, China was hit by several cold events during the early winter of 2020/21. The lowest temperature observed at Beijing station on 7 January reached −19.6°C. In this paper, we show that the outbreak of the record-breaking extreme cold event can be attributed to a huge merging Ural blocking (UB) ridge over the Eurasian region. The sea-ice cover in the Kara and East Siberia Seas (KESS) in autumn was at its lowest value since 1979, which could have served as a precursor signal. Further analysis shows that several successive UB episodes occurred from 1 September 2020 to 10 January 2021. The persistent UB that occurred in late September/early October 2020 may have made an important contribution to the October historical minimum of sea ice in the KESS region. Our results also show that, after each UB episode in winter, significant upward propagation of wave activity occurred around 60°E, which resulted in weakening the stratospheric vortex. Meanwhile, each UB episode also caused a significant reduction in sea-ice extent in KESS and a significant weakening of the westerly jet in mid–high-latitude Eurasia. Results suggest that the Arctic vortex, which is supposed to enhance seasonally, became weaker and more unstable than the climatic mean under the seasonal cumulative effects of UB episodes, KESS warming, and long-lasting negative-phase North Atlantic Oscillation (NAO–). Those seasonal cumulative effects, combined with the impact of La Niña winter, led to the frequent occurrence of extreme cold events.
Risk factors for lymph node metastasis and prognosis in colorectal neuroendocrine tumours
Authors: Zheng Xiuli , Wu Mingli , Er Limian , Deng Huiyan , Wang Gongning , Jin Lingyao , Li Shengmian
Published: January 2022

Purpose

The detection rate of colorectal neuroendocrine tumours (CR-NETs) is increasing, but their treatment is still controversial. Lymph node metastasis is an important reference index for the selection of treatment. The aim of our study was to investigate the factors associated with lymph node metastasis and prognosis of CR-NETs.

Methods

The case characteristics of patients with colorectal neuroendocrine tumours from January 2011 to December 2020 were retrospectively analysed, including age, gender, tumour size, tumour location, lymph node metastasis, pathological grade and follow-up.

Results

A total of 195 cases of CR-NETs were included in this study. When 15 mm was used as the cut-off value, the sensitivity, specificity and area under the curve (AUC) of lymph node metastases were 95.9%, 95.2% and 0.986, respectively. Multivariate analysis suggested that tumour size ≥ 15 mm (OR: 30.517, 95% CI: 1.250 ~ 744.996, p = 0.036) and lymphovascular invasion (OR: 42.796, 95% CI: 2.882 ~ 635.571, p = 0.006) were independent risk factors for lymph node metastasis. Age ≥ 56 (HR: 7.434, 95% CI: 1.334 ~ 41.443, p = 0.022) and distant metastasis (HR: 24.487, 95% CI: 5.357 ~ 111.940, p < 0.001) were independent prognostic factors in multivariable analyses.

Conclusions

When the size of a CR-NET is ≥ 15 mm, the risk of lymph node metastasis is higher, and it is recommended to choose the surgical method carefully. Tumour size and lymphovascular invasion were independent risk factors for lymph node metastasis. Age ≥ 56 and distant metastasis were independent prognostic factors.
Biomarkers as predictors of recurrence of atrial fibrillation post ablation: an updated and expanded systematic review and meta-analysis
Authors: Boyalla Vennela , Harling Leanne , Snell Alice , Kralj-Hans Ines , Barradas-Pires Ana , Haldar Shouvik , Khan Habib R. , Cleland John G. F. , Athanasiou Thanos , Harding Sian E. , Wong Tom
Published: January 2022

Background

A high proportion of patients undergoing catheter ablation (CA) for atrial fibrillation (AF) experience recurrence of arrhythmia. This meta-analysis aims to identify pre-ablation serum biomarker(s) associated with arrhythmia recurrence to improve patient selection before CA.

Methods

A systematic approach following PRISMA reporting guidelines was utilised in libraries (Pubmed/Medline, Embase, Web of Science, Scopus) and supplemented by scanning through bibliographies of articles. Biomarker levels were compared using a random-effects model and presented as odds ratio (OR). Heterogeneity was examined by meta-regression and subgroup analysis.

Results

In total, 73 studies were identified after inclusion and exclusion criteria were applied. Nine out of 22 biomarkers showed association with recurrence of AF after CA. High levels of N-Terminal-pro-B-type-Natriuretic Peptide [OR (95% CI), 3.11 (1.80–5.36)], B-type Natriuretic Peptide [BNP, 2.91 (1.74–4.88)], high-sensitivity C-Reactive Protein [2.04 (1.28–3.23)], Carboxy-terminal telopeptide of collagen type I [1.89 (1.16–3.08)] and Interleukin-6 [1.83 (1.18–2.84)] were strongly associated with identifying patients with AF recurrence. Meta-regression highlighted that AF type had a significant impact on BNP levels (heterogeneity R2 = 55%). Subgroup analysis showed that high BNP levels were more strongly associated with AF recurrence in paroxysmal AF (PAF) cohorts compared to the addition of non-PAF patients. Egger’s test ruled out the presence of publication bias from small-study effects.

Conclusion

Ranking biomarkers based on the strength of association with outcome provides each biomarker relative capacity to predict AF recurrence. This will provide randomised controlled trials, a guide to choosing a priori tool for identifying patients likely to revert to AF, which are required to substantiate these findings.

Graphical abstract
Bioactive fish collagen peptides weaken intestinal inflammation by orienting colonic macrophages phenotype through mannose receptor activation
Authors: Rahabi Mouna , Salon Marie , Bruno-Bonnet Christelle , Prat Mélissa , Jacquemin Godefroy , Benmoussa Khaddouj , Alaeddine Mohamad , Parny Mélissa , Bernad José , Bertrand Bénédicte , Auffret Yannick , Robert-Jolimaître Pascale , Alric Laurent , Authier Hélène , Coste Agnès
Published: January 2022

Purpose

Particular interest is now given to the potential of dietary supplements as alternative non-pharmacological approaches in intestinal inflammation handling. In this aim, this study evaluates the efficiency of fish collagen peptides, Naticol®Gut, on colonic inflammation.

Methods

Wild type and Mannose receptor-deficient in the myeloid lineage C57BL/6 mice were administered with Dextran Sodium Sulfate (DSS), Naticol®Gut, DSS, and Naticol®Gut or only water for 4 or 8 days. Inflammatory status was evaluated by establishing macroscopic and microscopic scores, by measuring cytokine and calprotectin production by ELISA and the myeloperoxidase activity by chemiluminescence. Colonic macrophages were phenotyped by measuring mRNA levels of specific markers of inflammation and oxidative status. Colonic immune populations and T-cell activation profiles were determined by flow cytometry. Mucosa-associated gut microbiota assessment was undertaken by qPCR. The phenotype of human blood monocytes from inflammatory bowel disease (IBD) subjects was characterized by RT-qPCR and flow cytometry and their oxidative activity by chemiluminescence.

Results

Naticol®Gut-treated DSS mice showed attenuated colonic inflammation compared to mice that were only exposed to DSS. Naticol®Gut activity was displayed through its ability to orient the polarization of colonic macrophage towards an anti-inflammatory and anti-oxidant phenotype after its recognition by the mannose receptor. Subsequently, Naticol®Gut delivery modulated CD4 T cells in favor of a Th2 response and dampened CD8 T-cell activation. This immunomodulation resulted in an intestinal eubiosis. In human monocytes from IBD subjects, the treatment with Naticol®Gut also restored an anti-inflammatory and anti-oxidant phenotype.

Conclusion

Naticol®Gut acts as a protective agent against colitis appearing as a new functional food and an innovative and complementary approach in gut health.
Neurological update: treatment escalation in multiple sclerosis patients refractory to fingolimod—potentials and risks of subsequent highly active agents
Authors: Korsen Melanie , Pfeuffer Steffen , Rolfes Leoni , Meuth Sven G. , Hartung Hans-Peter
Published: January 2022

A critical issue in the management of relapsing MS (RMS) is the discontinuation of disease-modifying treatments (DMT) due to lack of efficacy, intolerability or impending risks. With new therapeutic agents introduced into the treatment of RMS, immediate- and long-term consequences of sequential drug use, as well as the effect of the sequence in which the drugs are given, are unclear but may affect efficacy, adverse events, and long-term immunocompetence. In the absence of clinical studies specifically addressing these concerns, observations from clinical practice are of particular value in guiding current management algorithms. Prompted by a study published by Ferraro et al. in this journal, we set out to provide an overview of the published real-world evidence on the effectiveness and safety of switching from fingolimod to another DMT in patients with active RMS. Seventeen publications reporting relevant information were identified. The literature suggests that immune cell depletion induced by alemtuzumab or ocrelizumab is associated with an increased risk of relapse and worsening disability in patients switching from fingolimod compared to patients switching from other therapeutic agents. However, the evidence reported for natalizumab and cladribine is inconclusive. While shortening of the washout period may limit early disease reactivation after fingolimod discontinuation, there is no strong evidence that the duration of the washout period or the absolute lymphocyte count at baseline are predictors of attenuated long-term efficacy. Further real-world studies are required to better understand outcomes among patients who are under-represented in controlled trials.
Preoperative neutrophil-to-lymphocyte ratio behaves as an independent prognostic factor even in patients with postoperative complications after curative resection for gastric cancer
Authors: Tur-Martínez Jaume , Osorio Javier , Pérez-Romero Noelia , Puértolas-Rico Noelia , Pera Manuel , Delgado Salvadora , Rodríguez-Santiago Joaquín
Published: January 2022

Purpose

The aim of this study was to determine if the prognostic value of the preoperative neutrophil-to-lymphocyte ratio (NLR) could be modified by the presence of postoperative complications (POC) and their severity in patients with gastric adenocarcinoma resected with curative intent.

Methods

A retrospective study based on a prospective database of patients with resectable gastric adenocarcinoma treated with radical intention (R0) between January 1998 and February 2012. The primary endpoint was overall survival according to preoperative peripheral blood NLR and postoperative complications. Clinicopathological variables, preoperative blood tests, POC and its severity (Clavien–Dindo classification), type of POC (infectious or not infectious) and mortality were registered. A univariate and multivariate analysis (step forward Cox regression) was performed. The Kaplan–Meier method was used to assess overall survival.

Results

The 147 patients with gastric cancer who had undergone radical resection were included from an initial cohort of 209 patients. Univariant analysis: type of surgery, pT, pN, postoperative complications (Clavien–Dindo ≥ 3) and preoperative NLR ≥ 2.4 were significantly associated with survival (p < 0.05). Patients with POC showed worse long-term survival (p = 0.000), with no difference (p = 0.867) between infectious or non-infectious POC. NLR ≥ 2.4 was associated with infectious POC (p < 0.001). Patients with preoperative NLR ≥ 2.4 (p = 0.02) had a worse prognosis. Multivariate analysis: pN (p < 0.001), postoperative complications (p < 0.001) (HR 3.04; 95% CI: 1.97–4.70) and NLR ≥ 2.4 (p = 0.04) (HR = 1.55; 95% CI: 1.02–2.3) were independent prognostic factors.

Conclusion

The preoperative inflammatory state of patients with gastric cancer measured by NLR behaves as an independent prognostic factor, even in patients with POC.
The process-disruption hypothesis: how spelling and typing skill affects written composition process and product
Authors: Rønneberg Vibeke , Torrance Mark , Uppstad Per Henning , Johansson Christer
Published: January 2022

This study investigates the possibility that lack of fluency in spelling and/or typing disrupts writing processes in such a way as to cause damage to the substance (content and structure) of the resulting text. 101 children (mean age 11 years 10 months), writing in a relatively shallow orthography (Norwegian), composed argumentative essays using a simple text editor that provided accurate timing for each keystroke. Production fluency was assessed in terms of both within-word and word-initial interkey intervals and pause counts. We also assessed the substantive quality of completed texts. Students also performed tasks in which we recorded time to pressing keyboard keys in response to spoken letter names (a keyboard knowledge measure), response time and interkey intervals when spelling single, spoken words (spelling fluency), and interkey intervals when typing a simple sentence from memory (transcription fluency). Analysis by piecewise structural equation modelling gave clear evidence that all three of these measures predict fluency when composing full text. Students with longer mid-word interkey intervals when composing full text tended to produce texts with slightly weaker theme development. However, we found no other effects of composition fluency measures on measures of the substantive quality of the completed text. Our findings did not, therefore, provide support for the process-disruption hypothesis, at least in the context of upper-primary students writing in a shallow orthography.
Motor restrictions impair divergent thinking during walking and during sitting
Authors: Murali Supriya , Händel Barbara
Published: January 2022

Creativity, specifically divergent thinking, has been shown to benefit from unrestrained walking. Despite these findings, it is not clear if it is the lack of restriction that leads to the improvement. Our goal was to explore the effects of motor restrictions on divergent thinking for different movement states. In addition, we assessed whether spontaneous eye blinks, which are linked to motor execution, also predict performance. In experiment 1, we compared the performance in Guilford’s alternate uses task (AUT) during walking vs. sitting, and analysed eye blink rates during both conditions. We found that AUT scores were higher during walking than sitting. Albeit eye blinks differed significantly between movement conditions (walking vs. sitting) and task phase (baseline vs. thinking vs. responding), they did not correlate with task performance. In experiment 2 and 3, participants either walked freely or in a restricted path, or sat freely or fixated on a screen. When the factor restriction was explicitly modulated, the effect of walking was reduced, while restriction showed a significant influence on the fluency scores. Importantly, we found a significant correlation between the rate of eye blinks and creativity scores between subjects, depending on the restriction condition. Our study shows a movement state-independent effect of restriction on divergent thinking. In other words, similar to unrestrained walking, unrestrained sitting also improves divergent thinking. Importantly, we discuss a mechanistic explanation of the effect of restriction on divergent thinking based on the increased size of the focus of attention and the consequent bias towards flexibility.
Long COVID symptoms and duration in SARS-CoV-2 positive children — a nationwide cohort study
Authors: Borch Luise , Holm Mette , Knudsen Maria , Ellermann-Eriksen Svend , Hagstroem Soeren
Published: January 2022

Most children have a mild course of acute COVID-19. Only few mainly non-controlled studies with small sample size have evaluated long-term recovery from SARS-CoV-2 infection in children. The aim of this study was to evaluate symptoms and duration of ‘long COVID’ in children. A nationwide cohort study of 37,522 children aged 0–17 years with RT-PCR verified SARS-CoV-2 infection (response rate 44.9%) and a control group of 78,037 children (response rate 21.3%). An electronic questionnaire was sent to all children from March 24th until May 9th, 2021. Symptoms lasting > 4 weeks were common among both SARS-CoV-2 children and controls. However, SARS-CoV-2 children aged 6–17 years reported symptoms more frequently than the control group (percent difference 0.8%). The most reported symptoms among pre-school children were fatigue Risk Difference (RD) 0.05 (CI 0.04–0.06), loss of smell RD 0.01 (CI 0.01–0.01), loss of taste RD 0.01 (CI 0.01–0.02) and muscle weakness RD 0.01 (CI 0.00–0.01). Among school children the most significant symptoms were loss of smell RD 0.12 (CI 0.12–0.13), loss of taste RD 0.10 (CI 0.09–0.10), fatigue RD 0.05 (CI 0.05–0.06), respiratory problems RD 0.03 (CI 0.03–0.04), dizziness RD 0.02 (CI 0.02–0.03), muscle weakness RD 0.02 (CI 0.01–0.02) and chest pain RD 0.01 (CI 0.01–0.01). Children in the control group experienced significantly more concentration difficulties, headache, muscle and joint pain, cough, nausea, diarrhea and fever than SARS-CoV-2 infected. In most children ‘long COVID’ symptoms resolved within 1–5 months.

Conclusions: Long COVID in children is rare and mainly of short duration.

What is Known:• There are increasing reports on ‘long COVID’ in adults.• Only few studies have evaluated the long-term recovery from COVID-19 in children, and common for all studies is a small sample size (median number of children included 330), and most lack a control group.

What is New:• 0.8% of SARS-CoV-2 positive children reported symptoms lasting >4 weeks (‘long COVID’), when compared to a control group.• The most common ‘long COVID’ symptoms were fatigue, loss of smell and loss of taste, dizziness, muscle weakness, chest pain and respiratory problems.• These ‘long COVID’ symptoms cannot be assigned to psychological sequelae of social restrictions.• Symptoms such as concentration difficulties, headache, muscle- and joint pain as well as nausea are not ‘long COVID’ symptoms.• In most cases ‘long COVID’ symptoms resolve within 1-5 months.
Prognostic value of hepatocyte growth factor for muscle-invasive bladder cancer
Authors: Katayama Satoshi , Schuettfort Victor M. , Pradere Benjamin , Mori Keiichiro , Mostafaei Hadi , Quhal Fahad , Sari Motlagh Reza , Laukhtina Ekaterina , Grossmann Nico C. , Aydh Abdulmajeed , Rajwa Pawel , König Frederik , Karakiewicz Pierre I. , Haydter Martin , Moschini Marco , Abufaraj Mohammad , Lotan Yair , Lee Richard K. , Trinh Quoc-Dien , Compérat Eva , Teoh Jeremy , Nasu Yasutomo , Shariat Shahrokh F.
Published: January 2022

Purpose

The HGF/MET pathway is involved in cell motility, angiogenesis, proliferation, and cancer invasion. We assessed the clinical utility of plasma HGF level as a prognostic biomarker in patients with MIBC.

Methods

We retrospectively analyzed 565 patients with MIBC who underwent radical cystectomy. Logistic regression and Cox regression models were used, and predictive accuracies were estimated using the area under the curve and concordance index. To estimate the clinical utility of HGF, DCA and MCID were applied.

Results

Plasma HGF level was significantly higher in patients with advanced pathologic stage and LN metastasis (p = 0.01 and p < 0.001, respectively). Higher HGF levels were associated with an increased risk of harboring LN metastasis and non-organ-confined disease (OR1.21, 95%CI 1.12–1.32, p < 0.001, and OR1.35, 95%CI 1.23–1.48, p < 0.001, respectively) on multivariable analyses; the addition of HGF improved the predictive accuracies of a standard preoperative model (+ 7%, p < 0.001 and + 8%, p < 0.001, respectively). According to the DCA and MCID, half of the patients had a net benefit by including HGF, but the absolute magnitude remained limited. In pre- and postoperative predictive models, a higher HGF level was significant prognosticator of worse RFS, OS, and CSS; in the preoperative model, the addition of HGF improved accuracies by 6% and 5% for RFS and CSS, respectively.

Conclusion

Preoperative HGF identified MIBC patients who harbored features of clinically and biologically aggressive disease. Plasma HGF could serve, as part of a panel, as a biomarker to aid in preoperative treatment planning regarding intensity of treatment in patients with clinical MIBC.
CD147 expression lacks prognostic relevance in esophageal cancer
Authors: Küsters Natalie , Grupp Katharina , Grass Julia-Kristin , Bachmann Kai , Ghadban Tarik , Uzunoglu Faik G. , Tachezy Michael , Perez Daniel , Reeh Matthias , Izbicki Jakob R. , Melling Nathaniel
Published: January 2022

Introduction

The role of CD147 as an important indicator of tumor prognosis remains controversially discussed in literature. We focused on the prognostic significance of CD147 expression in esophageal cancer patients. While some studies report that CD147 is an unfavorable prognostic factor in esophageal squamous cell carcinoma, others showed no significant correlation. However, only one study draws attention to the significance of CD147 in esophageal adenocarcinoma, which is one of the most rapidly increasing neoplasms in the western world.

Methods

To finally clarify the impact of CD147 as a prognostic factor, especially for esophageal adenocarcinomas, we analyzed CD147 expression in a tissue microarray of 359 esophageal adenocarcinomas and 254 esophageal squamous cell cancer specimens. For the immuno-histochemical analysis, we used a primary antibody specific for CD147. Staining intensity and proportion of positive tumor cells were scored (negative, weak, moderate, strong staining). These findings were compared to normal esophageal tissue and correlated to the histopathological tumor phenotype and survival data.

Results

CD147 expression was detectable in weak intensities in benign esophageal tissue (85.78%) and expressed in predominately moderate to strong intensities in esophageal cancer (88.34%). Strong CD147 immunostaining was linked to increased infiltration depth (p = 0.015) and differentiation (p = 0.016) in esophageal squamous cell cancer but revealed no significant correlation with histopathology of adenocarcinoma. Moreover, CD147 intensity was unrelated to overall survival in this collective for both subtypes of esophageal cancer.

Conclusion

Thus, our data show that CD147 has no prognostic value, neither in esophageal adenocarcinoma nor squamous cell carcinoma.
Cancer worry among BRCA1/2 pathogenic variant carriers choosing surgery to prevent tubal/ovarian cancer: course over time and associated factors
Authors: van Bommel Majke H. D. , Steenbeek Miranda P. , IntHout Joanna , Hermens Rosella P. M. G. , Hoogerbrugge Nicoline , Harmsen Marline G. , van Doorn Helena C. , Mourits Marian J. E. , van Beurden Marc , Zweemer Ronald P. , Gaarenstroom Katja N. , Slangen Brigitte F. M. , Brood-van Zanten Monique M. A. , Vos M. Caroline , Piek Jurgen M. , van Lonkhuijzen Luc R. C. W. , Apperloo Mirjam J. A. , Coppus Sjors F. P. J. , Prins Judith B. , Custers José A. E. , de Hullu Joanne A.
Published: January 2022

Objective

High cancer risks, as applicable to BRCA1 and BRCA2 pathogenic variant (PV) carriers, can induce significant cancer concerns. We examined the degree of cancer worry and the course of this worry among BRCA1/2-PV carriers undergoing surgery to prevent ovarian cancer, and identified factors associated with high cancer worry.

Methods

Cancer worry was evaluated as part of the multicentre, prospective TUBA-study (NCT02321228) in which BRCA1/2-PV carriers choose either novel risk-reducing salpingectomy with delayed oophorectomy or standard risk-reducing salpingo-oophorectomy. The Cancer Worry Scale was obtained before and 3 and 12 months after surgery. Cancer worry patterns were analysed using latent class growth analysis and associated factors were identified with regression analysis.

Results

Of all 577 BRCA1/2-PV carriers, 320 (57%) had high (≥ 14) cancer worry pre-surgery, and 54% had lower worry 12 months post-surgery than pre-surgery. Based on patterns over time, BRCA1/2-PV carriers could be classified into three groups: persistently low cancer worry (56%), persistently high cancer worry (6%), and fluctuating, mostly declining, cancer worry (37%). Factors associated with persistently high cancer concerns were age below 35 (BRCA1) or 40 (BRCA2), unemployment, previous breast cancer, lower education and a more recent BRCA1/2-PV diagnosis.

Conclusions

Some degree of cancer worry is considered normal, and most BRCA1/2-PV carriers have declining cancer worry after gynaecological risk-reducing surgery. However, a subset of these BRCA1/2-PV carriers has persisting major cancer concerns up to 1 year after surgery. They should be identified and potentially offered additional support.

Clinical trial registration

The TUBA-study is registered at ClinicalTrials.gov since December 11th, 2014. Registration number: NCT02321228.
Rockfall and Rainfall Correlation in the Anaga Nature Reserve in Tenerife (Canary Islands, Spain)
Authors: Leyva Sergio , Cruz-Pérez Noelia , Rodríguez-Martín Jesica , Miklin Luka , Santamarta Juan C.
Published: January 2022

Rockfalls are frequent and damaging phenomena that occur on steep or vertical slopes, in coastal areas, mountains and along coastal cliff. Water, in different forms, is the most common triggered factor of rockfalls. Consequently, we can consider that precipitation is the most influential factor for slope instabilities and it influences almost all other water parameters. Besides, the specific geology of the Anaga nature reserve in the volcanic island of Tenerife, together with its steep landscape, contributes to the instability of the slopes and frequent rockfalls. Recently, due to climate change and global warming, the annual precipitation/rainfall has declined but the number of heavy storms, associated with intense rainfall and strong winds, events that exceed precipitation thresholds in a brief period has increased which triggers slope movements. This paper describes the analysis of information on rainfall-induced rockfalls in Anaga, Tenerife (Canary Islands), to forecast rock failures of social significance and to improve the capability to respond and emergency decision making. To define reliable thresholds for a certain area, we analized information during the period 2010–2016, reconstructed the rockfall events, and statistically analyzed the historical rainfall conditions that led to landslides. The summary graph correlating precipitation to the probability of occurrence of an event was plotted. Statistical and probability graphs were made with the direct relationship between the number of rockfall events and total rainfall in that period by examining the maximum daily precipitation, not only on the day of the event but up to 3 days before. Hence, the results of this study would serve as a guide for the possible forecasting of rainfall-induced rockfalls, especially for road maintenance services, so that they can be on alert or mobilize the necessary resources in advance depending on the intensity of the expected rainfall.
Review: Horizontal, directionally drilled and radial collector wells
Authors: Houben Georg J. , Collins Sarah , Bakker Mark , Daffner Thomas , Triller Falk , Kacimov Anvar
Published: January 2022

Horizontal wells play an often overlooked role in hydrogeology and aquifer remediation but can be an interesting option for many applications. This study reviews the constructional and hydraulic aspects that distinguish them from vertical wells. Flow patterns towards them are much more complicated than those for vertical wells, which makes their mathematical treatment more demanding. However, at some distance, the drawdown fields of both well types become practically identical, allowing simplified models to be used. Due to lower drawdowns, the yield of a horizontal well is usually higher than that of a vertical well, especially in thin aquifers of lower permeability, where they can replace several of the latter. The lower drawdown, which results in lower energy demand and slower ageing, and the centralized construction of horizontal wells can lead to lower operational costs, which can make them an economically feasible option.
Efficacy and safety of trifluridine/tipiracil in older and younger patients with metastatic gastric or gastroesophageal junction cancer: subgroup analysis of a randomized phase 3 study (TAGS)
Authors: Shitara Kohei , Doi Toshihiko , Hosaka Hisashi , Thuss-Patience Peter , Santoro Armando , Longo Federico , Ozyilkan Ozgur , Cicin Irfan , Park David , Zaanan Aziz , Pericay Carles , Özgüroğlu Mustafa , Alsina Maria , Makris Lukas , Benhadji Karim A. , Ilson David H.
Published: January 2022

Background

Trifluridine and tipiracil (FTD/TPI) demonstrated survival benefit vs placebo and manageable safety in previously treated patients with metastatic gastric/gastroesophageal junction cancer (mGC/GEJC) in the randomized, placebo-controlled, phase 3 TAGS study. This subgroup analysis of TAGS examined efficacy/safety outcomes by age.

Methods

In TAGS, patients with mGC/GEJC and ≥ 2 prior therapies were randomized (2:1) to receive FTD/TPI 35 mg/m2 or placebo, plus best supportive care. A preplanned subgroup analysis was performed to evaluate efficacy and safety outcomes in patients aged < 65, ≥ 65, and ≥ 75 years.

Results

Among 507 randomized patients (n = 337 FTD/TPI; n = 170 placebo), 55%, 45%, and 14% were aged < 65, ≥ 65, and ≥ 75 years, respectively. Overall survival hazard ratios for FTD/TPI vs placebo were 0.67 (95% CI 0.51–0.89), 0.73 (95% CI 0.52–1.02), and 0.67 (95% CI 0.33–1.37) in patients aged < 65, ≥ 65, and ≥ 75 years, respectively. Regardless of age, patients receiving FTD/TPI experienced improved progression-free survival and stayed longer on treatment than those receiving placebo. Among FTD/TPI-treated patients, frequencies of any-cause grade ≥ 3 adverse events (AEs) were similar across age subgroups (80% each), although grade ≥ 3 neutropenia was more frequent in older patients [40% (≥ 65 and ≥ 75 years); 29% (< 65 years)]; AE-related discontinuation rates did not increase with age [14% (< 65 years), 12% (≥ 65 years), and 12% (≥ 75 years)].

Conclusions

The results of this subgroup analysis show the efficacy and tolerability of FTD/TPI treatment regardless of age in patients with mGC/GEJC who had received 2 or more prior treatments.
Certification of açaí agroforestry increases the conservation potential of the Amazonian tree flora
Authors: Damasco Gabriel , Anhalt Mandy , Perdiz Ricardo O. , Wittmann Florian , de Assis Rafael L. , Schöngart Jochen , Piedade Maria T. F. , Bacon Christine D. , Antonelli Alexandre , Fine Paul V. A.
Published: January 2022

The harvesting of açaí berries (palm fruits from the genus Euterpe) in Amazonia has increased over the last 20 years due to a high local and global market demand and triggered by their widely acclaimed health benefits as a ‘superfood’. Although such increase represents a financial boom for local communities, unregulated extraction in Amazonia risks negative environmental effects including biodiversity loss through açai intensification and deforestation. Alternatively, the introduction of certified sustainable agroforestry production programs of açaí has been strategically applied to reduce the exploitation of Amazonian forests. Local açaí producers are required to follow principles of defined sustainable management practices, environmental guidelines, and social behaviors, paying specific attention to fair trade and human rights. In this study we investigate whether sustainable agroforestry and certification effectively promotes biodiversity conservation in Amazonia. To address this question, we conducted a forestry inventory in two hectares of long-term certified açai harvesting areas to gain further knowledge on the plant diversity and forest structure in açaí managed forests and to understand the contribution of certification towards sustainable forest management. On average, we found that certified managed forests harbor 50% more tree species than non-certified açaí groves. Trees in certified areas also have significantly higher mean basal area, meaning larger and hence older individuals are more likely to be protected. Certified harvesting sites also harbor dense populations of threatened species as classified by the International Union for Conservation of Nature (e.g. Virola surinamensis, classified as ‘endangered’). Besides increasing the knowledge of plant diversity in açaí managed areas, we present baseline information for monitoring the impact of harvesting activities in natural ecosystems in Amazonia.
Diagnostic and predictive accuracy of anti-mullerian hormone for ovarian function after chemotherapy in premenopausal women with early breast cancer
Authors: Anderson Richard A. , Kelsey Tom W. , Perdrix Anne , Olympios Nathalie , Duhamel Orianne , Lambertini Matteo , Clatot Florian
Published: January 2022

Purpose

Accurate diagnosis and prediction of loss of ovarian function after chemotherapy for premenopausal women with early breast cancer (eBC) is important for future fertility and clinical decisions regarding the need for subsequent adjuvant ovarian suppression. We have investigated the value of anti-mullerian hormone (AMH) as serum biomarker for this.

Methods

AMH was measured in serial blood samples from 206 premenopausal women aged 40–45 years with eBC, before and at intervals after chemotherapy. The diagnostic accuracy of AMH for loss of ovarian function at 30 months after chemotherapy and the predictive value for that of AMH measurement at 6 months were analysed.

Results

Undetectable AMH showed a high diagnostic accuracy for absent ovarian function at 30 months with AUROC 0.89 (96% CI 0.84–0.94, P < 0.0001). PPV of undetectable AMH at 6 months for a menopausal estradiol level at 30 months was 0.77. In multivariate analysis age, pre-treatment AMH and FSH, and taxane treatment were significant predictors, and combined with AMH at 6 months, gave AUROC of 0.90 (95% CI 0.86–0.94), with PPV 0.79 for loss of ovarian function at 30 months. Validation by random forest models with 30% data retained gave similar results.

Conclusions

AMH is a reliable diagnostic test for lack of ovarian function after chemotherapy in women aged 40–45 with eBC. Early analysis of AMH after chemotherapy allows identification of women who will not recover ovarian function with good accuracy. These analyses will help inform treatment decisions regarding adjuvant endocrine therapy in women who were premenopausal before starting chemotherapy.