bluuebunny/crossref_metadata_2025 huggingface dataset:
Extracellular vesicle release and uptake by the liver under normo- and hyperlipidemia
Authors: Németh Krisztina , Varga Zoltán , Lenzinger Dorina , Visnovitz Tamás , Koncz Anna , Hegedűs Nikolett , Kittel Ágnes , Máthé Domokos , Szigeti Krisztián , Lőrincz Péter , O’Neill Clodagh , Dwyer Róisín , Liu Zhonglin , Buzás Edit I. , Tamási Viola
Published: October 2021

Liver plays a central role in elimination of circulating extracellular vesicles (EVs), and it also significantly contributes to EV release. However, the involvement of the different liver cell populations remains unknown. Here, we investigated EV uptake and release both in normolipemia and hyperlipidemia. C57BL/6 mice were kept on high fat diet for 20–30 weeks before circulating EV profiles were determined. In addition, control mice were intravenously injected with 99mTc-HYNIC-Duramycin labeled EVs, and an hour later, biodistribution was analyzed by SPECT/CT. In vitro, isolated liver cell types were tested for EV release and uptake with/without prior fatty acid treatment. We detected an elevated circulating EV number after the high fat diet. To clarify the differential involvement of liver cell types, we carried out in vitro experiments. We found an increased release of EVs by primary hepatocytes at concentrations of fatty acids comparable to what is characteristic for hyperlipidemia. When investigating EV biodistribution with 99mTc-labeled EVs, we detected EV accumulation primarily in the liver upon intravenous injection of mice with medium (326.3 ± 19.8 nm) and small EVs (130.5 ± 5.8 nm). In vitro, we found that medium and small EVs were preferentially taken up by Kupffer cells, and liver sinusoidal endothelial cells, respectively. Finally, we demonstrated that in hyperlipidemia, there was a decreased EV uptake both by Kupffer cells and liver sinusoidal endothelial cells. Our data suggest that hyperlipidema increases the release and reduces the uptake of EVs by liver cells. We also provide evidence for a size-dependent differential EV uptake by the different cell types of the liver. The EV radiolabeling protocol using 99mTc-Duramycin may provide a fast and simple labeling approach for SPECT/CT imaging of EVs biodistribution.
Head and neck tumor cells treated with hypofractionated irradiation die via apoptosis and are better taken up by M1-like macrophages
Authors: Wedekind Hanna , Walz Kristina , Buchbender Mayte , Rieckmann Thorsten , Strasser Erwin , Grottker Fridolin , Fietkau Rainer , Frey Benjamin , Gaipl Udo S , Rückert Michael
Published: October 2021

Purpose

The incidence of head and neck squamous cell carcinomas (HNSCC) is increasing worldwide, especially when triggered by the human papilloma virus (HPV). Radiotherapy has immune-modulatory properties, but the role of macrophages present in HNSCC and having contact with irradiated tumor cells remains unclear. The influence of irradiated (2 × 5Gy) HNSCC cells on the (re-)polarization and phagocytosis of human macrophages, either non-polarized or with a more M1 or M2 phenotype, was therefore investigated.

Methods

Human monocytes were differentiated with the hematopoietic growth factors M‑CSF (m) or GM-CSF (g) and additionally pre-polarized with either interleukin (IL)-4 and IL-10 or interferon (IFN)-γ and lipopolysaccharides (LPS), respectively. Subsequently, they were added to previously irradiated (2 × 5Gy) and mock-treated HPV-positive (UD-SCC-2) and HPV-negative (Cal33) HNSCC cells including their supernatants.

Results

The HNSCC cells treated with hypofractionated irradiation died via apoptosis and were strongly phagocytosed by M0m and M2 macrophages. M0g and M1 macrophages phagocytosed the tumor cells to a lesser extent. Irradiated HNSCC cells were better phagocytosed by M1 macrophages compared to mock-treated controls. The polarization status of the macrophages was not significantly changed, except for the expression of CD206 on M2 macrophages, which was reduced after phagocytosis of irradiated HPV-negative cells. Further, a significant increase in the uptake of irradiated HPV-positive cells by M0g macrophages when compared to HPV-negative cells was observed.

Conclusion

HNSCC cells treated with hypofractionated irradiation foster phagocytosis by anti-tumorigenic M1 macrophages. The data provide the first evidence on the impact of the HPV status of HNSCC cells on the modulation of the macrophage response to irradiated tumor cells.
Hohe Krankheitslast bei Patienten mit ANCA-assoziierter Vaskulitis
Authors: Haller H. G. , von Vietinghoff S. , Spearpoint P. , Deichmann A. , Buchholz I. , Schönermark M. P. , Rutherford P. , Götte D.
Published: October 2021

Hintergrund und Zielsetzung

Unter dem Begriff der mit antineutrophilen zytoplasmatischen Antikörpern (ANCA) assoziierten Vaskulitis (AAV) wird eine Gruppe seltener, chronischer, durch rezidivierende systemische Entzündungen gekennzeichneter Autoimmunerkrankungen mit vielfältigen Morbiditäten zusammengefasst. Patienten mit AAV leiden unter diversen Organmanifestationen und schweren Nebenwirkungen der Therapie. In dieser retrospektiven Studie wurde die konkrete Belastung der Patienten durch die AAV-Erkrankung in Deutschland untersucht.

Methodik

Basierend auf anonymisierten Längsschnittdaten der gesetzlichen Krankenversicherung (GKV) zur medizinischen Versorgung zwischen 2013 und 2016 wurden aus einer repräsentativen Kohorte von etwa 3 Mio. Versicherten Patienten mit Granulomatose mit Polyangiitis (GPA) und mikroskopischer Polyangiitis (MPA) identifiziert und ausgewählte klinische Aspekte systematisch analysiert.

Ergebnisse

Die häufigsten begleitenden Morbiditäten von GPA und MPA waren Nieren- und Atemwegserkrankungen. Eine schwere Nierenbeteiligung trat bei 11,6 % der GPA- und 24,3 % der MPA-Patienten innerhalb von 15 Quartalen nach der Diagnose auf. Bei einem Drittel der Patienten mit AAV entwickelten sich innerhalb der ersten 3 Quartale nach Diagnose schwere Infektionen. Die Rate der schweren Rezidive betrug jährlich 5–8 %. Patienten mit AAV und Nierenbeteiligung oder Infektionen zeigten zudem eine hohe jährliche Mortalitätsrate von 14,4 % bzw. 5,6 %.

Schlussfolgerung

Anhand dieser Analyse deutscher Versorgungsdaten wurden krankheitsspezifische Annahmen der Belastung von Patienten mit AAV bestätigt und für den deutschen Kontext konkretisiert. Patienten mit AAV leiden unter einer hohen Morbiditätsbelastung, einschließlich multipler Krankheitsmanifestationen, Rezidiven und schwerer Komplikationen aufgrund der AAV-Therapie.
Zur Anwendbarkeit der dentalen Methode von Roberts et al. aus dem Jahr 2016 zum Nachweis der Vollendung des 18. Lebensjahres lebender Personen
Authors: Timme M. , Borkert J. , Steffens L. , Shay D. , Schmeling A.
Published: October 2021

Es sollte die Methode von Roberts et al. aus dem Jahr 2016 zum Nachweis der Vollendung des 18. Lebensjahres überprüft werden.

Dazu wurden 603 Orthopantomogramme (OPG) von 300 Frauen und 303 Männern im Alter von 16,01 bis 25,99 Jahren von 3 Untersuchern ausgewertet, wobei ein Hauptuntersucher alle OPGs zweimal begutachtet hat. Durch die 3 Untersucher wurde eine konsensuale Bestimmung für die Fälle vorgenommen, bei denen mindestens ein Untersucher ein Stadium zugeordnet hatte.

In 31 Fällen (11 Frauen, 20 Männer) konnte konsensuell ein Stadium bestimmt werden. Hauptursache für die Nichtauswertbarkeit war die nicht abgeschlossene Entwicklung des Zahnes 38 [FDI] (30,18 %), gefolgt von Karies, Restaurationen oder anderen Pathologien (20,56 %) und dem Fehlen des Zahnes 38 (19,57 %). Das Stadium „RCW‑C“ konnte bei den Frauen konsensual nicht, die Stadien „RCW‑B“ und „RCW‑C“ konnten bei den Männern nur 4‑mal (3x „RCW-C“, 1x „RCW-B“) bestimmt werden. Der Cohen’s-Kappa-Wert für die Binnenbeobachterübereinstimmung für die 47 Fälle, in denen der Hauptuntersucher in mindestens einem Durchgang ein Stadium zugeordnet hatte, lag im moderaten bzw. guten Bereich (Frauen: 0,44; Männer: 0,62). Der Fleiss’-Kappa-Wert für die Zwischenbeobachterübereinstimmung der 3 Untersucher für die 69 Fälle, bei denen mindestens ein Untersucher ein Stadium zugeordnet hatte, lag im mangelhaften Bereich (Frauen: 0,07; Männer: 0,11), wobei die 95%-Konfidenzintervalle für den Kappa-Wert auch die „0“ einschlossen.

Alle Personen, bei denen ein Stadium zugeordnet wurde, waren über 18 Jahre alt. Aktuell kann eine Anwendung der Methode nicht empfohlen werden. Es wird die Frage aufgeworfen, ob den Stadien eine allgemeingültige Entwicklungsabfolge zu Grunde zu liegt, da bei 30 Fällen der Befund nicht mit den Stadien in Deckung zu bringen war.
Die Abgrenzung der Fremdtötung von der eigenverantwortlichen Selbsttötung: Doppelsuizid, erweiterter Suizid oder Homizid-Suizid?
Authors: Dietz E. , Schädler J. , Püschel K. , Ondruschka B.
Published: October 2021

In der Literatur finden sich vielfach Publikationen und Kasuistiken, die sich mit zeitlich, örtlich, partnerschaftlich und/oder familiär im Zusammenhang stehenden nichtnatürlichen Todesfälle unabhängig von der Art und Weise zweier oder mehrerer Personen auseinandersetzen. Im Nachfolgenden sollen jene Fälle genauer betrachtet werden, bei denen zumindest in einem der Fälle naheliegt, dass es sich beispielsweise aufgrund der Spurenlage um einen freiverantwortlichen Suizidentschluss gehandelt hat. Diese werden u. a. als „erweiterte Suizide“ oder in jüngerer Zeit auch als „Homizid-Suizide“ bezeichnet. Diese theoriespezifizierten Nomenklaturen finden sich nicht zuletzt deshalb berechtigt kritisiert, als dass die Motive, genauen Tatumstände und Tathintergründe oftmals nicht bekannt sind und somit eine (vorgreifende) Wertung erfolgt, ohne dass andere mögliche Tathergänge zur Diskussion gestanden hätten. Daher stellt sich zunächst die Frage nach der generellen und konkreten Eignung dieser Nomenklaturen hinsichtlich ihrer Anwendbarkeit, mit der sich daran anschließenden Überlegung einer neu zu definierenden übergeordneten Bezeichnung. Die Komplexität dieser Begrifflichkeiten soll im Nachfolgenden an dem gemeinsamen Tod eines älteren Ehepaares verdeutlicht werden.
Special cycles on toroidal compactifications of orthogonal Shimura varieties
Authors: Bruinier Jan Hendrik , Zemel Shaul
Published: October 2021

We determine the behavior of automorphic Green functions along the boundary components of toroidal compactifications of orthogonal Shimura varieties. We use this analysis to define boundary components of special divisors and prove that the generating series of the resulting special divisors on a toroidal compactification is modular.
Pharmacokinetics of cannabichromene in a medical cannabis product also containing cannabidiol and Δ9-tetrahydrocannabinol: a pilot study
Authors: Peters Erica N. , MacNair Laura , Mosesova Irina , Christians Uwe , Sempio Cristina , Klawitter Jost , Land M. Hunter , Ware Mark A. , Turcotte Cynthia , Bonn-Miller Marcel O.
Published: October 2021

Purpose

Cannabichromene (CBC) is a phytocannabinoid commonly found in cannabis, yet its acute post-dose pharmacokinetics (PK) have not been examined in humans. This is a secondary data analysis from a trial investigating Spectrum Yellow oil, an oral cannabis product used for medical purposes that contained 20 mg cannabidiol (CBD), 0.9 mg Δ9-tetrahydrocannabinol (THC), and 1.1 mg CBC, per 1 mL of oil.

Methods

Participants (N = 43) were randomized to one of 5 groups: 120 mg CBD, 5.4 mg THC, and 6.6 mg CBC daily; 240 mg CBD, 10.8 mg THC, and 13.2 mg CBC daily; 360 mg CBD, 16.2 mg THC, and 19.8 mg CBC daily; 480 mg CBD, 21.6 mg THC, and 26.4 mg CBC daily; or placebo. Study medication was administered every 12 h for 7 days. Plasma CBC concentrations were analyzed by a validated two-dimensional high-performance liquid chromatography–tandem mass spectrometry assay.

Results

After a single dose and after the final dose, the Cmax of CBC increased by 1.3–1.8-fold for each twofold increase in dose; the tmax range was 1.6–4.3 h. Based on the ratio of administered CBD, THC, and CBC to the plasma concentration, the dose of CBD was 18 times higher than the dose of CBC, yet the AUC0–t of CBD was only 6.6–9.8-fold higher than the AUC0–t of CBC; the dose of THC was similar to the dose of CBC, yet THC was quantifiable in fewer plasma samples than was CBC.

Conclusions

CBC may have preferential absorption over CBD and THC when administered together.

Trial Registration: Australian New Zealand Clinical Trials Registry #ACTRN12619001450101, registered 18 October 2019.
Differential role of residual metabolic tumor volume in inoperable stage III NSCLC after chemoradiotherapy ± immune checkpoint inhibition
Authors: Unterrainer Marcus , Taugner Julian , Käsmann Lukas , Tufman Amanda , Reinmuth Niels , Li Minglun , Mittlmeier Lena M. , Bartenstein Peter , Kunz Wolfgang G. , Ricke Jens , Belka Claus , Eze Chukwuka , Manapov Farkhad
Published: October 2021

Background

The PET-derived metabolic tumor volume (MTV) is an independent prognosticator in non-small cell lung cancer (NSCLC) patients. We analyzed the prognostic value of residual MTV (rMTV) after completion of chemoradiotherapy (CRT) in inoperable stage III NSCLC patients with and without immune checkpoint inhibition (ICI).

Methods

Fifty-six inoperable stage III NSCLC patients (16 female, median 65.0 years) underwent 18F-FDG PET/CT after completion of standard CRT. rMTV was delineated on 18F-FDG PET/CT using a standard threshold (liver SUVmean + 2 × standard deviation). 21/56 patients underwent additional ICI (CRT-IO, 21/56 patients) thereafter. Patients were divided in volumetric subgroups using median split dichotomization (MTV ≤ 4.3 ml vs. > 4.3 ml). rMTV, clinical features, and ICI-application were correlated with clinical outcome parameters (progression-free survival (PFS), local PFS (LPFS), and overall survival (OS).

Results

Overall, median follow-up was 52.0 months. Smaller rMTV was associated with longer median PFS (29.3 vs. 10.5 months, p = 0.015), LPFS (49.9 vs. 13.5 months, p = 0.001), and OS (63.0 vs. 23.0 months, p = 0.003). CRT-IO patients compared to CRT patients showed significantly longer median PFS (29.3 vs. 11.2 months, p = 0.034), LPFS (median not reached vs. 14.0 months, p = 0.016), and OS (median not reached vs. 25.2 months, p = 0.007). In the CRT subgroup, smaller rMTV was associated with longer median PFS (33.5 vs. 8.6 months, p = 0.001), LPFS (49.9 vs. 10.1 months, p = 0.001), and OS (63.0 vs. 16.3 months, p = 0.004). In the CRT-IO subgroup, neither PFS, LPFS, nor OS were associated with MTV (p > 0.05 each). The findings were confirmed in subsequent multivariate analyses.

Conclusion

In stage III NSCLC, smaller rMTV is highly associated with superior clinical outcome, especially in patients undergoing CRT without ICI. Patients with CRT-IO show significantly improved outcome compared to CRT patients. Of note, clinical outcome in CRT-IO patients is independent of residual MTV. Hence, even patients with large rMTV might profit from ICI despite extensive tumor load.
Prognostic factors in children and adolescents with differentiated thyroid carcinoma treated with total thyroidectomy and RAI: a real-life multicentric study
Authors: Cistaro Angelina , Quartuccio Natale , Garganese Maria Carmen , Villani Maria Felicia , Altini Claudio , Pizzoferro Milena , Piccardo Arnoldo , Cabria Manlio , Massollo Michela , Maghnie Mohamad , Campennì Alfredo , Siracusa Massimiliano , Baldari Sergio , Panareo Stefano , Urso Luca , Bartolomei Mirco , De Palma Diego , Grossi Armando , Mazzoletti Angelica , Dondi Francesco , Bertagna Francesco , Giubbini Raffaele , Albano Domenico
Published: October 2021

Purpose

This multicentric study aimed to investigate the main prognostic factors associated with treatment response at 1 year after radioactive iodine therapy (RAIT) and the last disease status in pediatric patients affected by differentiated thyroid carcinoma (DTC).

Materials and methods

In the period 1990–2020, all consecutive patients ≤ 18 years from six different centers were retrospectively included. Patients were classified as low, intermediate, and high risk for persistence/recurrence. The response to RAIT was evaluated and scored 1 year later according to 2015 ATA guidelines. Moreover, at the last follow-up, the disease status was evaluated and dichotomized as no evidence of disease (NED) or persistent disease.

Results

Two hundred and eighty-five patients (197 female, 88 male; mean age 14.4 years) were recruited. All, except nine, underwent near-total thyroidectomy followed by RAIT. One-year after first RAIT, 146/276 (53%) patients had excellent response, 37/276 (14%) indeterminate response, and 91/276 (33%) incomplete response. One-year after RAIT, children with excellent response had significantly lower stimulated thyroglobulin (sTg) compared to not excellent group (median sTg 4.4 ng/ml vs 52.5 ng/ml, p < 0.001). ROC curve showed sTg higher than 27.2 ng/ml as the most accurate to predict 1-year treatment response. After a median follow-up of 133 months, NED was present in 241 cases (87%) while persistent disease in 35 (13%). At multivariate analysis, sTg and 1-year treatment response categories were both significantly associated with the last disease status (p value 0.023 and < 0.001).

Conclusions

In pediatric DTC, sTg is significantly associated with 1-year treatment response and final outcome. However, 1-year response is the principal prognostic factor able to predict pediatric DTCs outcome.
Prognostic Factors and Lymph Node Metastasis Patterns of Primary Duodenal Cancer
Authors: Nishio Kohei , Kimura Kenjiro , Eguchi Shimpei , Shirai Daisuke , Tauchi Jun , Kinoshita Masahiko , Murata Akihiro , Ohira Go , Shinkawa Hiroji , Shintaro Kodai , Amano Ryosuke , Tanaka Shogo , Shimizu Sadatoshi , Takemura Shigekazu , Kanazawa Akishige , Kubo Shoji
Published: October 2021

Background

The effectiveness and extent of regional lymph node dissection in primary duodenal cancer (DC) remains unclear. This study aimed to analyze the prognostic factors and lymph node metastasis (LNM) patterns in DC.

Methods

Fifty‐three patients who underwent surgical resection for DC between January 1998 and December 2018 at two institutions were retrospectively analyzed. Univariate and multivariate analyses were performed on the prognostic factors of resected DC. Moreover, the relationships between depth of tumor invasion and incidence of LNM and between tumor location and LNM stations were analyzed.

Results

The five‐year survival rate of the study population was 68.9%. Multivariate survival analysis demonstrated that histologic grade G2–G4, presence of LNM, pT3–4, and elevated preoperative CA19‐9 were the independent poor prognostic factors. No patient with pTis–T2 had LNM. On the other hand, LNM was found in 70% of patients with pT3–4. Among 36 patients who underwent pancreaticoduodenectomy (PD), LNM around the pancreatic head was observed, regardless of the duodenal cancer site, including the duodenal bulb and the third to the fourth portion.

Conclusions

Histologic grade G2–G4, presence of LNM, pT3–T4, and elevated preoperative CA19‐9 were the independent poor prognostic factors in patients with resected DC. Our results suggested that lymph node dissection could be omitted for DC Tis–T1a. Moreover, based on the high frequency of LNM in T3–4 cases, PD with lymph node dissection in the pancreatic head region was considered necessary for T3–4 DC at any site.
Acute Kidney Injury within an Enhanced Recovery after Surgery (ERAS) Program for Colorectal Surgery
Authors: Drakeford Paul Andrew , Tham Shu Qi , Kwek Jia Li , Lim Vera , Lim Chien Joo , How Kwang Yeong , Ljungqvist Olle
Published: October 2021

Background

We aimed to determine the prevalence, risk factors, and outcomes of acute kidney injury (AKI) within an ERAS program for colorectal surgery (CRS).

Methods

This is a retrospective case–control study conducted from March 2016 to September 2018 at a single tertiary hospital in Singapore. All adult patients requiring CRS within our ERAS program were considered eligible. Exclusions were stage 5 chronic kidney disease or patients requiring a synchronous liver resection. The primary outcome was AKI as defined by the Kidney Disease Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. Secondary outcomes included mortality, major complications, and hospital length of stay. Patient, surgical, and anaesthesia‐related data were analysed to determine factors associated with AKI.

Results

A total of 575 patients were eligible for the study. Twenty patients were excluded from the study leaving 555 patients for analysis. Mean age was 67.8 (SD 11.4) years. Seventy‐four patients met the criteria for AKI (13.4%: stage 1—11.2%, stage 2—2.0%, stage 3—0.2%). One patient required renal replacement therapy (RRT). Patients with AKI had a longer length of stay (median [IQR], 11.0 [5.0–17.0] days vs 6.0 [4.0–8.0] days; P < .001), more major complications (OR, 6.55; 95% CI, 3.00–14.35, P < .001), and a trend towards higher mortality at one year (OR, 1.44; 95% CI 0.48–4.30; p = 0.511. After multivariable regression analysis, factors associated with AKI were preoperative creatinine (OR, 1.01 per 10 µmol/l; 95% CI, 1.03–1.22; P = 0.01), robotic surgery vs open surgery (OR, 0.15; 95% CI, 0.06–0.39; P < 0.001), anaesthesia duration (OR, 1.38 per hour; 95% CI, 1.22–1.55; P < 0.001), and major complications (OR, 5.55; 95% CI, 2.63–11.70; P < 0.001).

Conclusions

Within the present cohort, the implementation of an ERAS program for CRS was associated with a low prevalence of moderate to severe AKI despite a balanced intravenous fluid regimen. Patients having open surgery, longer procedures, and major complications are at increased risk of AKI.
Peripartale psychische Belastung und Auswirkungen auf die frühe Elternschaft
Authors: Stuhrmann Lydia Yao , Göbel Ariane , Mudra Susanne
Published: October 2021

Hintergrund

Peripartale elterliche Angst und Depressivität zeigten Zusammenhänge mit kindlichen emotionalen und Verhaltensauffälligkeiten. Mögliche Erklärungsansätze umfassen pränatal prägende Einflüsse auf das Ungeborene sowie das postpartale Fortwirken psychischer Belastung auf die Eltern-Kind-Beziehung. Dabei kommt dem elterlichen Vertrauen in die eigenen Fähigkeiten eine mögliche protektive Rolle zu, das wiederum durch die eigene psychische Belastung und das kindliche Verhalten maßgeblich beeinträchtigt sein kann.

Fragestellung

Diese Studie untersucht, wie sich pränatale schwangerschaftsspezifische Ängste auf das Vertrauen in die eigenen Fähigkeiten als Mutter in der frühen Elternschaft auswirken und wodurch dieser Effekt vermittelt wird.

Material und Methoden

Als Teil einer prospektiven Längsschnittstudie beantworteten 116 Mütter im letzten Schwangerschaftsdrittel (T0) und der 3. Woche (T1) postpartal Fragebögen zu schwangerschaftsspezifischen Ängsten, mütterlichem Selbstvertrauen, postpartaler Depressivität und kindlicher Irritabilität.

Ergebnisse

Es zeigte sich, dass der Zusammenhang zwischen pränatalen Ängsten und mangelndem mütterlichen Selbstvertrauen nicht über das Erleben kindlicher Irritabilität, sondern entscheidend über das Erleben postpartaler Depressivität vermittelt wurde. Die mütterliche Parität spielte ebenfalls eine Rolle.

Schlussfolgerung

Pränatale schwangerschaftsspezifische Ängste können postpartaler Depressivität vorausgehen und so indirekt das mütterliche Vertrauen in die eigenen Fähigkeiten beeinträchtigen. Die Wachsamkeit für elterliche psychische Belastung und die Weiterentwicklung von Behandlungsansätzen mit Beginn in der Schwangerschaft sind notwendig und erfordern eine enge interprofessionelle Zusammenarbeit zwischen eltern- und kindbezogenen Disziplinen.
Low skeletal muscle mass assessed directly from the 3rd cervical vertebra can predict pharyngocutaneous fistula risk after total laryngectomy in the male population
Authors: Casasayas Maria , García-Lorenzo Jacinto , Gómez-Ansón Beatriz , Medina Victoria , Fernández Alejandro , Quer Miquel , León Xavier
Published: October 2021

Purpose

Skeletal muscle mass (SMM) loss and sarcopenia have been identified as risk factors for postoperative complications. The aim of this study was to investigate the relationship between pharyngocutaneous fistula (PCF) formation after total laryngectomy (TL) and SMM assessed from a computed tomography image of the 3rd cervical vertebra (C3).

Methods

Retrospective study of 86 male patients who underwent TL between 2013 and 2019 in a single institution. We excluded women from the analysis due to our limited sample. SMM was determined from cross-sectional muscle area (CSMA) measurement at C3 using the ImageJ software. Results were compared with those for the skeletal muscle mass index (SMMI) calculated from the estimated measure at 3rd lumbar vertebra (L3).

Results

PCF formation occurred in 21/86 patients. According to the CSMA at a C3 cut-off of 35.5cm2, of 18 patients (20.9%) with low SMM, 9 developed PCFs (50.0%). Among patients with normal SMM (n = 68, 79.1%), 12 developed PCFs (17.6%). The CSMA at C3 was the only variable significantly associated with PCF risk, which was 4.7 times greater in patients with low SMM (p = 0.007). Sarcopenia was more frequent in underweight patients (p = 0.0001), patients undergoing extended surgeries (p = 0.003), or presenting preoperative anaemia (p = 0.009) or hypoalbuminemia (p = 0.027).

Conclusion

Measuring the CSMA at C3 obtained results equivalent to those obtained by calculating the SMMI at L3, suggesting that direct SMM assessment from C3 is a useful approach to evaluating PCF formation risk after TL.
Causes of irritant contact dermatitis after occupational skin exposure: a systematic review
Authors: Jacobsen Gitte , Rasmussen Kurt , Bregnhøj Anne , Isaksson Marléne , Diepgen Thomas L. , Carstensen Ole
Published: October 2021

Purpose

Irritant contact dermatitis (ICD) is a major cause of occupational disease. The aim was to review the relation between exposure to occupational irritants and ICD and the prognosis of ICD.

Methods

Through a systematic search, 1516 titles were identified, and 48 studies were included in the systematic review.

Results

We found that the evidence for an association between ICD and occupational irritants was strong for wet work, moderate for detergents and non-alcoholic disinfectants, and strong for a combination. The highest quality studies provided limited evidence for an association with use of occlusive gloves without other exposures and moderate evidence with simultaneous exposure to other wet work irritants. The evidence for an association between minor ICD and exposure to metalworking fluids was moderate. Regarding mechanical exposures, the literature was scarce and the evidence limited. We found that the prognosis for complete healing of ICD is poor, but improves after decrease of exposure through change of occupation or work tasks. There was no substantial evidence for an influence of gender, age, or household exposures. Inclusion of atopic dermatitis in the analysis did not alter the risk of ICD. Studies were at risk of bias, mainly due to selection and misclassification of exposure and outcome. This may have attenuated the results.

Conclusion

This review reports strong evidence for an association between ICD and a combination of exposure to wet work and non-alcoholic disinfectants, moderate for metalworking fluids, limited for mechanical and glove exposure, and a strong evidence for a poor prognosis of ICD.
Beyond Ca2+ signalling: the role of TRPV3 in the transport of NH4+
Authors: Liebe Hendrik , Liebe Franziska , Sponder Gerhard , Hedtrich Sarah , Stumpff Friederike
Published: October 2021

Mutations of TRPV3 lead to severe dermal hyperkeratosis in Olmsted syndrome, but whether the mutants are trafficked to the cell membrane or not is controversial. Even less is known about TRPV3 function in intestinal epithelia, although research on ruminants and pigs suggests an involvement in the uptake of NH4+. It was the purpose of this study to measure the permeability of the human homologue (hTRPV3) to NH4+, to localize hTRPV3 in human skin equivalents, and to investigate trafficking of the Olmsted mutant G573S. Immunoblotting and immunostaining verified the successful expression of hTRPV3 in HEK-293 cells and Xenopus oocytes with trafficking to the cell membrane. Human skin equivalents showed distinct staining of the apical membrane of the top layer of keratinocytes with cytosolic staining in the middle layers. Experiments with pH-sensitive microelectrodes on Xenopus oocytes demonstrated that acidification by NH4+ was significantly greater when hTRPV3 was expressed. Single-channel measurements showed larger conductances in overexpressing Xenopus oocytes than in controls. In whole-cell experiments on HEK-293 cells, both enantiomers of menthol stimulated influx of NH4+ in hTRPV3 expressing cells, but not in controls. Expression of the mutant G573S greatly reduced cell viability with partial rescue via ruthenium red. Immunofluorescence confirmed cytosolic expression, with membrane staining observed in a very small number of cells. We suggest that expression of TRPV3 by epithelia may have implications not just for Ca2+ signalling, but also for nitrogen metabolism. Models suggesting how influx of NH4+ via TRPV3 might stimulate skin cornification or intestinal NH4+ transport are discussed.
EGFR transcriptionally upregulates UTX via STAT3 in non-small cell lung cancer
Authors: Zhou Lin , Wang Xiaomu , Lu Jingya , Fu Xiangning , Li Yangkai
Published: October 2021

Background

Histone demethylase UTX has been reported to participate in the occurrence and development of many cancers in tissue-specific manners. However, the role of UTX in non-small cell lung cancer (NSCLC) and exactly what regulates the expression of UTX remains unclear. Here, we analyzed the role of UTX in NSCLC in association with the widely recognized tumor driver epidermal growth factor receptor (EGFR).

Methods

UTX levels in clinical samples were detected by immunohistochemistry staining, western blotting and real-time quantitative PCR. The expression of UTX in tumor tissue was correlated with the phosphorylation of EGFR. Cell proliferation and migration were evaluated by MTT and wound-healing assays. The impact of EGFR and its downstream pathways on UTX was explored with corresponding inhibitors, and examined by western blotting and real-time quantitative PCR.

Results

In this study, we found that the expression of UTX in cancer tissues of patients with NSCLC was significantly higher than that in paracancerous tissues, and positively associated with EGFR phosphorylation levels. In addition, in NSCLC cell lines, UTX can promote proliferation and migration, while inhibition of its enzyme activity suppressed cell growth. Moreover, UTX expression was significantly upregulated when EGFR signaling pathway was activated, and vice versa when EGFR pathway was inhibited by tyrosine kinase inhibitor. Further mechanistic studies suggested that the activation of EGFR activated its downstream JAK/STAT3 signaling pathway and promoted STAT3 phosphorylation; the phosphorylated STAT3 transcriptionally promoted the levels of UTX.

Conclusions

These results suggest an “EGFR-STAT3-UTX” axis that plays an oncogenic role in NSCLC.
Machine learning classification of conduct disorder with high versus low levels of callous-unemotional traits based on facial emotion recognition abilities
Authors: Pauli Ruth , Kohls Gregor , Tino Peter , Rogers Jack C. , Baumann Sarah , Ackermann Katharina , Bernhard Anka , Martinelli Anne , Jansen Lucres , Oldenhof Helena , Gonzalez-Madruga Karen , Smaragdi Areti , Gonzalez-Torres Miguel Angel , Kerexeta-Lizeaga Iñaki , Boonmann Cyril , Kersten Linda , Bigorra Aitana , Hervas Amaia , Stadler Christina , Fernandez-Rivas Aranzazu , Popma Arne , Konrad Kerstin , Herpertz-Dahlmann Beate , Fairchild Graeme , Freitag Christine M. , Rotshtein Pia , De Brito Stephane A.
Published: October 2021

Conduct disorder (CD) with high levels of callous-unemotional traits (CD/HCU) has been theoretically linked to specific difficulties with fear and sadness recognition, in contrast to CD with low levels of callous-unemotional traits (CD/LCU). However, experimental evidence for this distinction is mixed, and it is unclear whether these difficulties are a reliable marker of CD/HCU compared to CD/LCU. In a large sample (N = 1263, 9–18 years), we combined univariate analyses and machine learning classifiers to investigate whether CD/HCU is associated with disproportionate difficulties with fear and sadness recognition over other emotions, and whether such difficulties are a reliable individual-level marker of CD/HCU. We observed similar emotion recognition abilities in CD/HCU and CD/LCU. The CD/HCU group underperformed relative to typically developing (TD) youths, but difficulties were not specific to fear or sadness. Classifiers did not distinguish between youths with CD/HCU versus CD/LCU (52% accuracy), although youths with CD/HCU and CD/LCU were reliably distinguished from TD youths (64% and 60%, respectively). In the subset of classifiers that performed well for youths with CD/HCU, fear and sadness were the most relevant emotions for distinguishing them from youths with CD/LCU and TD youths, respectively. We conclude that non-specific emotion recognition difficulties are common in CD/HCU, but are not reliable individual-level markers of CD/HCU versus CD/LCU. These findings highlight that a reduced ability to recognise facial expressions of distress should not be assumed to be a core feature of CD/HCU.
Long-Term Drought and Warming Alter Soil Bacterial and Fungal Communities in an Upland Heathland
Authors: Seaton Fiona M. , Reinsch Sabine , Goodall Tim , White Nicola , Jones Davey L. , Griffiths Robert I. , Creer Simon , Smith Andy , Emmett Bridget A. , Robinson David A.
Published: October 2021

The response of soil microbial communities to a changing climate will impact global biogeochemical cycles, potentially leading to positive and negative feedbacks. However, our understanding of how soil microbial communities respond to climate change and the implications of these changes for future soil function is limited. Here, we assess the response of soil bacterial and fungal communities to long-term experimental climate change in a heathland organo-mineral soil. We analysed microbial communities using Illumina sequencing of the 16S rRNA gene and ITS2 region at two depths, from plots undergoing 4 and 18 years of in situ summer drought or warming. We also assessed the colonisation of Calluna vulgaris roots by ericoid and dark septate endophytic (DSE) fungi using microscopy after 16 years of climate treatment. We found significant changes in both the bacterial and fungal communities in response to drought and warming, likely mediated by changes in soil pH and electrical conductivity. Changes in the microbial communities were more pronounced after a longer period of climate manipulation. Additionally, the subsoil communities of the long-term warmed plots became similar to the topsoil. Ericoid mycorrhizal colonisation decreased with depth while DSEs increased; however, these trends with depth were removed by warming. We largely ascribe the observed changes in microbial communities to shifts in plant cover and subsequent feedback on soil physicochemical properties, especially pH. Our results demonstrate the importance of considering changes in soil microbial responses to climate change across different soil depths and after extended periods of time.
Land Use Modeling Predicts Divergent Patterns of Change Between Upper and Lower Elevations in a Subalpine Watershed of the Alps
Authors: Anselmetto Nicolò , Sibona Emanuele Marco , Meloni Fabio , Gagliardi Luca , Bocca Massimo , Garbarino Matteo
Published: October 2021

The synergic influence of land use and climate change on future forest dynamics is hard to disentangle, especially in human-dominated forest ecosystems. Forest gain in mountain ecosystems often creates different spatial–temporal patterns between upper and lower elevation belts. We analyzed land cover dynamics over the past 50 years and predicted Business as Usual future changes on an inner subalpine watershed by using land cover maps, derived from five aerial images, and several topographic, ecological, and anthropogenic predictors. We analyzed historical landscape patterns through transition matrices and landscape metrics and predicted future forest ecosystem change by integrating multi-layer perceptron and Markov chain models for short-term (2050) and long-term (2100) timespans. Below the maximum timberline elevation of the year 1965, the dominant forest dynamic was a gap-filling process through secondary succession at the expense of open areas leading to an increase of landscape homogeneity. At upper elevations, the main observed dynamic was the colonization of unvegetated soil through primary succession and timberline upward shift, with an increasing speed over the last years. Future predictions suggest a saturation of open areas in the lower part of the watershed and stronger forest gain at upper elevations. Our research suggests an increasing role of climate change over the last years and on future forest dynamics at a landscape scale.
Relationships among inner strength, health and function, well-being, and negative life events in old people: a longitudinal study
Authors: Viglund Kerstin , Olofsson Birgitta , Lundman Berit , Norberg Astrid , Lövheim Hugo
Published: October 2021

Inner strength is a conceptualization of a human resource that is generally considered beneficial for health and well-being. Previously, it has been examined in qualitative and cross-sectional studies, but longitudinal data are lacking. The aim of this study was to examine how inner strength, health and function, well-being, and negative life events, namely crises and diseases, affect each other over time in old people. A longitudinal two-wave design was used with data from 2010 and 2016. A total of 4023 participants, living in Finland and Sweden, and born in 1930, 1935, 1940, or 1945 were included. Data were collected using the Inner Strength Scale, the Life Orientation Scale, a short version of the Geriatric Depression Scale, one item from the SF36, and five items from the Katz ADL-index. Structural equation modeling was used to test for cross-lagged effects. Crises and diseases were found to be a positive predictor of inner strength, a negative predictor of well-being, and to have no significant effect on health and function over time. Inner strength and well-being had a reciprocal positive relationship, and health and function was a positive predictor inner strength. The study expands findings by providing perspectives of inner strength across time indicating that inner strength in old people increases when they have to face a disease or crisis. From a health perspective, the present findings reinforce the importance of healthcare professionals’ awareness and knowledge of the construct of inner strength.
LatticeNet: fast spatio-temporal point cloud segmentation using permutohedral lattices
Authors: Rosu Radu Alexandru , Schütt Peer , Quenzel Jan , Behnke Sven
Published: October 2021

Deep convolutional neural networks have shown outstanding performance in the task of semantically segmenting images. Applying the same methods on 3D data still poses challenges due to the heavy memory requirements and the lack of structured data. Here, we propose LatticeNet, a novel approach for 3D semantic segmentation, which takes raw point clouds as input. A PointNet describes the local geometry which we embed into a sparse permutohedral lattice. The lattice allows for fast convolutions while keeping a low memory footprint. Further, we introduce DeformSlice, a novel learned data-dependent interpolation for projecting lattice features back onto the point cloud. We present results of 3D segmentation on multiple datasets where our method achieves state-of-the-art performance. We also extend and evaluate our network for instance and dynamic object segmentation.
Tuned-mass-damper-inerter optimal design and performance assessment for multi-storey hysteretic buildings under seismic excitation
Authors: Patsialis D. , Taflanidis A. A. , Giaralis A.
Published: October 2021

Inerter-based vibration absorbers (IVAs), such as the tuned-mass-damper-inerter (TMDI), have become popular in recent years for the earthquake protection of building structures. Previous studies using linear structural models have shown that IVAs can achieve enhanced vibration suppression, but at the expense of increased control forces exerted from the IVA to the host building structure. The authors recently developed a bi-objective IVA design framework for linearly behaving buildings to balance between structural performance (drift/acceleration suppression) and IVA forces. This paper extends the framework to multi-storey hysteretic/yielding structures under seismic excitation. Though the proposed design framework can accommodate any type of IVA, the focus is herein on TMDI applications, with tuned-mass-damper (TMD) and tuned-inerter-damper (TID) treated as special cases of the TMDI. Earthquake hazard is modeled through representative, design-level acceleration time-histories and response of the IVA-equipped structure is evaluated through nonlinear response-history analysis. A high-fidelity finite element model (FEM) is established to accurately describe hysteretic structural behavior. To reduce the computational burden, a reduced order model (ROM) is based on the original FEM, using the framework proposed recently by the first and second authors. The ROM maintains the accuracy of the original FEM while enabling for a computationally efficient solution to the optimization problem. As an illustrative example, the bi-objective design for different IVA placements along the height of a non-linear benchmark 9-storey steel frame structure is examined. The accuracy of the ROM-based design is evaluated by comparing performance to the FEM-based response predictions across the entire Pareto front resulting from the bi-objective optimization. Then, the designs and associated performance predicted by using a linear or a nonlinear structural model are compared to evaluate how the explicit consideration of nonlinearities, as well as the degree of nonlinear behavior, impact the IVA design and efficiency.
A Spatial Dynamic Model for Export Intensity of Hazardous Industrial Waste: The Incentive Effect of Regional Environmental Policies
Authors: Vallés-Giménez Jaime , Zárate-Marco Anabel
Published: October 2021

This paper analyses, in the context of the Environmental Kuznet Curve, the determinants of export intensity of hazardous industrial waste among Spanish regions, with particular attention to the influence of waste taxes and of environmental policies. This study is carried out for the first time in the literature with a spatial dynamic model, fixed effects and panel data for the 17 regions (Comunidades Autónomas) of Spain during the period 2007–2017. The results suggest there is a spatial-dynamic component to export intensity, and that both regional taxes on waste disposal and environmental policy stringency appear to encourage, albeit modestly, the rate of exported waste to other regions. The model also shows that the more regions recycle, and the greater the economies of scale arising from industrial agglomeration, the lower is the region’s waste export intensity, although increasing restrictions on the international trade in hazardous waste have intensified trading inside the country. Finally, the results suggest a non-linear relationship between growth and export intensity, although apparently we are still far from the absolute decoupling of the Environmental Kuznet Curve.
Household Preferences for Investing in Crowdfunding
Authors: Ciobotaru Laurentiu-Cristian , Kim Sul , van Soest Arthur
Published: October 2021

Using representative survey data on the Dutch population, we analyze households’ actual participation and stated preferences for crowdfunding involvement at the extensive and intensive margin, with emphasis on the relation with investing in socially responsible assets. We find that crowdfunding investors are higher educated and more future oriented than others, whereas risk aversion plays a negative but insignificant role. Financial literacy is positively associated with knowing about crowdfunding, but not with actual participation. A stated choice preference experiment largely confirms these relations. At the intensive margin, however, results are rather different: Women have a stronger preference for crowdfunding than men do. Financial literacy reduces the preferred share invested in crowdfunding. We find a strong positive relation between crowdfunding and socially responsible investing. We identify several common factors: a desire to contribute to improving society and a lack of confidence in traditional financial institutions. Comparing stated and revealed preferences, we find that the potential for attracting more crowdfunding funders is much smaller than for attracting socially responsible investors.
A Correlation Based Recommendation System for Large Data Sets
Authors: Pandove Divya , Malhi Avleen
Published: October 2021

Correlation determination brings out relationships in data that had not been seen before and it is imperative to successfully use the power of correlations for data mining. In this paper, we have used the concepts of correlations to cluster data, and merged it with recommendation algorithms. We have proposed two correlation clustering algorithms (RBACC and LGBACC), that are based on finding Spearman’s rank correlation coefficient among data points, and using dimensionality reduction approach (PCA) along with graph theory respectively, to produce high quality hierarchical clusters. Both these algorithms have been tested on real life data (New York yellow cabs dataset taken fromhttp://www.nyc.gov), using distributed and parallel computing (Spark and R). They are found to be scalable and perform better than the existing hierarchical clustering algorithms. These two approaches have been used to replace similarity measures in recommendation algorithms and generate a correlation clustering based recommendation system model. We have combined the power of correlation analysis with that of prediction analysis to propose a better recommendation system. It is found that this model makes better quality recommendations as compared to the random recommendation model. This model has been validated using a real time, large data set (MovieLens dataset, taken fromhttp://grouplens.org/datasets/movielens/latest). The results show that combining correlated points with the predictive power of recommendation algorithms, produce better quality recommendations which are faster to compute. LGBACC has approximately 25% better prediction capability but at the same time takes significantly more prediction time compared to RBACC.