bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost effectiveness and health-related quality of life of chemoradiotherapy versus radiation therapy alone in elderly head and neck cancer patients
Authors: Sprave Tanja , Verma Vivek , Fabian Alexander , Rühle Alexander , Baltas Dimos , Grosu Anca-Ligia , Nicolay Nils H.
Published: July 2022

Purpose

Radiotherapy (RT) constitutes a mainstay in the treatment of elderly patients with head and neck cancer (HNC), but use of simultaneous chemoradiotherapy (CRT) remains controversial. We have conducted a prospective analysis based on real-world patient data to examine the health-related quality of life (HRQoL) and cost effectiveness (CE) of CRT vs. RT in elderly HNC patients.

Methods

Eligible participants ≥ 65 years treated in a large tertiary cancer center between July 2019 and February 2020 who completed the validated EQ-5D-5L questionnaire (health state index [HI] and visual analog scale [VAS]) before and after RT were included. CE referred to direct medical costs, including diagnosis-related group (DRG)-based billings for inpatients and uniform assessment standard (EBM)-based costs for outpatients. The primary endpoint was cost (euros [€]) per quality-adjusted life year (QALY). The incremental cost-effectiveness ratios (ICERs) were calculated. Costs and QALYs were not discounted for short overall survival (OS).

Results

Baseline HRQoL was 0.878 (±0.11) in the CRT group and 0.857 (±0.17) in the RT group. Upon completion of therapy, HRQoL amounted to 0.849 (±0.14) in the CRT and 0.850 (±0.13) in the RT group. The mean treatment-related cost in the CRT cohort was €22,180.17 (±8325.26) vs. €18,027.87 (±26,022.48) in the RT group. The corresponding QALYs amounted to 2.62 in the CRT and 1.91 in the RT groups. The ICER was €5848.31.

Conclusion

This is the first analysis from the German health care system demonstrating that the addition of chemotherapy to RT for selected elderly HNC patients is cost effective and not associated with a significant HRQoL decline.
Inflammatory response to the ischaemia–reperfusion insult in the liver after major tissue trauma
Authors: Li Yang , Palmer Annette , Lupu Ludmila , Huber-Lang Markus
Published: July 2022

Background

Polytrauma is often accompanied by ischaemia–reperfusion injury to tissues and organs, and the resulting series of immune inflammatory reactions are a major cause of death in patients. The liver is one of the largest organs in the body, a characteristic that makes it the most vulnerable organ after multiple injuries. In addition, the liver is an important digestive organ that secretes a variety of inflammatory mediators involved in local as well as systemic immune inflammatory responses. Therefore, this review considers the main features of post-traumatic liver injury, focusing on the immuno-pathophysiological changes, the interactions between liver organs, and the principles of treatment deduced.

Methods

We focus on the local as well as systemic immune response involving the liver after multiple injuries, with emphasis on the pathophysiological mechanisms.

Results

An overview of the mechanisms underlying the pathophysiology of local as well as systemic immune responses involving the liver after multiple injuries, the latest research findings, and the current mainstream therapeutic approaches.

Conclusion

Cross-reactivity between various organs and cascade amplification effects are among the main causes of systemic immune inflammatory responses after multiple injuries. For the time being, the pathophysiological mechanisms underlying this interaction remain unclear. Future work will continue to focus on identifying potential signalling pathways as well as target genes and intervening at the right time points to prevent more severe immune inflammatory responses and promote better and faster recovery of the patient.
Malaria-Antigene in der Ära der mRNA-Impfstoffe
Authors: Borkens Yannick
Published: July 2022

Bereits in den frühen 1990er-Jahren wurde erstmals eine durch einen mRNA-Impfstoff ausgelöste Immunantwort beschrieben. Seitdem wurden mRNA-Impfstoffe für eine mögliche Prophylaxe erforscht und diskutiert. Doch erst mit der COVID-19-Pandemie erlebten diese Impfstoffe einen wahren Boom. Die ersten mRNA-Impfstoffe wurden gegen SARS-CoV‑2 zugelassen und zeigten große Erfolge. Es ist daher nicht verwunderlich, dass sich die Hersteller auch auf andere Krankheiten und Pathogene konzentrieren. Neben viralen Krankheiten wie Influenza oder Aids steht Malaria weit oben auf dieser Liste. Viele Pharmaunternehmen (u. a. die deutschen Unternehmen BioNTech und CureVac) haben bereits bestätigt, an mRNA-Impfstoffen gegen Malaria zu forschen. Dabei ist die Entwicklung eines funktionierenden Impfstoffes gegen Malaria kein leichtes Unterfangen. Seit den 1960ern wird an möglichen Impfstoffen geforscht. Die Ergebnisse sind dabei eher ernüchternd. Erst 2015 erhielt der Impfstoff RTS,S/AS01 eine positive Bewertung der Europäischen Arzneimittel-Agentur. Seitdem wird der Impfstoff in Afrika getestet.
Kombinierte intrapulmonale/intramediastinale K-Draht-Lage nach K-Draht-Osteosynthese an der Clavicula
Authors: Youssef Yasmin , Melcher Peter , Steinert Matthias , Metelmann Isabella , Hepp Pierre , Theopold Jan
Published: July 2022

Hintergrund

Laterale Clavicula-Frakturen können abhängig von der Klassifikation sowohl konservativ oder operativ behandelt werden. Für die operative Versorgung sind verschiedene Operationstechniken beschrieben. Die Wahl einer Operationstechnik ist für das funktionelle Outcome und für einen komplikationsarmen Heilungsverlauf ausschlaggebend.

Fallbeschreibung

Vorgestellt wird der Fall einer Patientin mit einer sekundären Dislokation zweier K‑Drähte nach K‑Draht-Osteosynthese. Im Rahmen einer sekundären Dislokation kam es zu einem Wandern des Drahtes in das Mediastinum und das Lungengewebe direkt unter den Aortenbogen. Zur Verhinderung weiterer Verletzungen konnte das chirurgische Fremdmaterial über eine uniportale videoassistierte Thorakoskopie geborgen werden.

Bei der Versorgung von lateralen Clavicula-Frakturen sollte auf eine instabile K‑Draht-Osteosynthese unbedingt verzichtet werden. Bei Vorliegen von sicheren Operationsverfahren (Plattenosteosynthese, Hybridversorgungen) sollten diese bevorzugt werden. Bei Durchführung primärer oder additiver K‑Draht-Osteosynthesen ist auf deren Sicherung z. B. durch Umbiegen zu achten, da es bei fehlerhafter Versorgung zu erheblichen Komplikationen, wie Pseudarthrose oder sekundären Dislokation des Materials, kommen kann.
Immunologie der Schwangerschaft: von lokalen und systemischen Protagonisten zum High-Content-Immunprofiling
Authors: Graf Isabel , Hecher Kurt , Arck Petra
Published: July 2022

Eine zielgerichtete Adaptation des mütterlichen Immunsystems an die Schwangerschaft ist essenziell, um einen komplikationslosen Schwangerschaftsverlauf zu ermöglichen. Hierfür ist ein komplexes Zusammenspiel von fetalen Trophoblastzellen, mütterlichen Immunzellen und dezidualen Stromazellen an der fetomaternalen Grenzzone notwendig. Auch systemisch erfolgen grundlegende immunologische Veränderungen. Darüber hinaus unterliegt die mütterliche Immunantwort einer zeitlichen Dynamik und passt sich den wechselnden Anforderungen der fortschreitenden Schwangerschaft an. Weiterhin unterliegt die mütterliche Immunantwort der Modulation von multiplen Einflussfaktoren, z. B. Hormonen. Im Beitrag werden Kernaspekte der immunologischen Adaptation an die Schwangerschaft beleuchtet, neuartige technologische Ansätze des Monitorings vorgestellt und klinische Anwendungspotenziale diskutiert.
Trajectory prediction of three-dimensional forming tube based on Kalman filter
Authors: Wu Jianjun , Liang Bo , Yang Junzhou
Published: July 2022

This article focuses on the prediction of forming trajectory and process optimization during the forming process for the variable curvature tubes. Firstly, through cubic B-spline interpolation, the geometric characteristics of the axis of the target tube are obtained. The whole tube is “separated and then integrated,” and the relationship between geometric parameters and processing parameters is established to obtain the initial process parameters. Based on the extended Kalman filter (EKF) algorithm, the motion model and observation model of tube forming are presented section by section, and the relevant calculation and analysis are carried out. The forming trajectory has been predicted; moreover, the processing parameters are optimized during the processing process, in which the effectiveness of the processing optimum scheme is illustrated.
Chemical composition and technofunctional properties of carrot (Daucus carota L.) pomace and potato (Solanum tuberosum L.) pulp as affected by thermomechanical treatment
Authors: Trabert Antje , Schmid Vera , Keller Judith , Emin M. Azad , Bunzel Mirko
Published: July 2022

Fiber rich by-products derived from primary agri-food production such as carrot pomace and potato pulp are available in large quantities, but their functional properties do not necessarily meet the requirements for use in specific food applications. Thermomechanical treatment (extrusion) of carrot pomace and potato pulp changes both dietary fiber polysaccharide structures and technofunctionality of the materials. Solubility of dietary fiber constituents changes, resulting in higher levels of water- and ethanol-soluble poly-/oligosaccharides. On a structural level, particularly arabinans and galactans as neutral side chains of type I rhamnogalacturonan were degraded under thermomechanical stress. Galacturonic acid portions (preferably from homogalacturonan or rhamnogalacturonan I) and their degree of methylation were also negatively affected. On a functional level, water absorption of potato pulp increased up to three times following extrusion, whereas water absorption of carrot pomace decreased with extrusion processing. The observed, enhanced swelling behavior for extruded carrot pomace was accompanied by higher complex viscosity of the dispersions. Swelling of potato pulp particles increased largely (up to 25 times) following extrusion, resulting in highly viscous pastes. Phytochemicals were retained up to 50%, heat-induced contaminants were formed only to a small extent (up to 8.1 mg 5-hydroxymethylfurfural·kg− 1 dry matter for carrot pomace; up to 71 µg acrylamide·kg− 1 dry matter for potato pulp).

Graphical abstract
Fracture Risk and Use of Angiotensin-Converting Enzyme Inhibitors or Angiotensin II Receptor Blockers
Authors: Holloway-Kew Kara L. , Betson Amelia G. , Anderson Kara B. , Sepetavc Filip , Gaston James , Kotowicz Mark A. , Liao Wan-Hui , Henneberg Maciej , Pasco Julie A.
Published: July 2022

Medications used to treat hypertension may affect fracture risk. This study investigated fracture risk for users of angiotensin converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB). Participants (899 men, median age 70.3 yr (59.9–79.1), range 50.0–96.6 yr; 574 women, median age 65.5 yr (58.1–75.4), range 50.1–94.6 yr) were from the Geelong Osteoporosis Study. Medication use was self-reported and incident fractures were ascertained using radiological reports. Bone mineral density (BMD) was measured at the femoral neck. Participants were divided into four groups: (1) non-users without hypertension, (2) non-users with hypertension, (3) ACEI users and (4) ARB users. Dosage was calculated using the defined daily dose (DDD) criteria. Participants were followed from date of visit to first fracture, death or 31 December 2016, whichever occurred first. Cox proportional hazards models were used for analyses. At least one incident fracture was sustained by 156 men and 135 women over a median(IQR) of 11.5(6.2–13.2) and 10.9(6.3–11.6) years of follow-up, respectively. In unadjusted analyses, compared to non-users without hypertension, men in all three other groups had a higher risk of fracture (Hazard Ratio (HR, 95%CI) 1.54, 1.00–2.37; 1.90, 1.18–3.05; 2.15, 1.26–3.66), for non-users with hypertension, ACEI and ARB users, respectively). Following adjustment for age, prior fracture and BMD, these associations became non-significant. A dose effect for ARB use was observed; men using lower doses had a higher risk of fracture than non-users without hypertension, in both unadjusted (2.66, 1.34–5.29) and adjusted (2.03, 1.01–4.08) analyses, but this association was not observed at higher doses. For women, unadjusted analyses showed a higher risk for ACEI users compared to non-users without hypertension (1.74, 1.07–2.83). This was explained after adjustment for age, alcohol consumption, prior fracture and BMD (1.28, 0.74–2.22). No other differences were observed. In men, lower dose (0 < DDD ≤ 1) ARB use was associated with an increased risk of fracture. ACEI or ARB use was not associated with increased risk of incident fracture in women. These findings may be important for antihypertensive treatment decisions in individuals with a high risk of fracture.
Population pharmacokinetic modelling of imatinib in healthy subjects receiving a single dose of 400 mg
Authors: Chien Yi-Han , Würthwein Gudrun , Zubiaur Pablo , Posocco Bianca , Pena María Ángeles , Borobia Alberto M. , Gagno Sara , Abad-Santos Francisco , Hempel Georg
Published: July 2022

Purpose

Imatinib is indicated for treatment of CML, GIST, etc. The population pharmacokinetics (popPK) of imatinib in patients under long-term treatment are reported in literature. Data obtained from bioequivalence trials for healthy subjects were used to evaluate the influence of demographic and pharmacogenetic factors on imatinib pharmacokinetics (PK) in a collective without concurrent drugs, organ dysfunction, inflammation etc. In addition, the differences in PK between the healthy subjects and a patient cohort was examined to identify possible disease effects.

Methods

26 volunteers were administered orally with single dose of 400 mg imatinib. 16–19 plasma samples per volunteer were collected from 0.5 up to 72 h post-dose. The popPK was built and post hoc estimates were compared with previously published PK parameters evaluated by non-compartmental analysis in the same cohort. The predictivity of the model for data collected from 40 patients with gastrointestinal stromal tumors at steady state was evaluated.

Results

The popPK was best described by a two-compartment transit model with first-order elimination. No significant covariates were identified, probably due to the small cohort and the narrow range of demographic covariates; CYP3A5 phenotypes appeared to have some influence on the clearance of imatinib. Good agreement between non-compartment and popPK analyses was observed with the differences of the geometric means/ median of PK estimates below 10%. The model indicated lower clearance for patients compared to healthy volunteers (p value < 0.01).

Conclusion

The two-compartment transit model adequately describes the absorption and distribution of imatinib in healthy volunteers. For patients, a lower clearance of imatinib compared to healthy volunteer was estimated by the model. The model can be applied for dose individualization based on trough concentrations assuming no significant differences in absorption between patients and healthy volunteers.
Prospective analysis of pain expectancy and experience during MR-fusion prostate biopsy: does reality match patients’ expectancy?
Authors: Krausewitz Philipp , Schmeller Helene , Luetkens Julian , Dabir Darius , Ellinger Jörg , Ritter Manuel , Conrad Rupert
Published: July 2022

Purpose

Multiparametric magnetic resonance imaging fusion targeted prostate biopsy (MR-TB) has emerged to the biopsy technique of choice for evaluation of patients with suspected prostate cancer (PCA). The study aimed to determine expected and experienced pain during MR-TB depending on patients’ psychological state.

Methods

We prospectively enrolled 108 men with suspicion of PCA who underwent MR-TB. All patients completed self-reported validated questionnaires assessing pain, stress, self-efficacy, anxiety and study-specific questionnaires on expected and experienced pain before, during and after MR-TB. Patient characteristics and survey scores were obtained.

Results

Overall, pain levels during MR-TB were low (mean 2.8/10 ± 2.5 Numerical Rating Scale, NRS). 10/86 (11.6%) participants reported severe pain (≥ 7/10 NRS). Pain correlated significantly with anxiety (r = 0.42), stress (r = 0.22) and pain expectancy (r = 0.58). High self-efficacy did not show increased pain resilience. Participants anticipated more pain than experienced during each step of MR-TB with significant differences concerning local anesthesia and core sampling (both p < 0.001), among others. Expectancy and actual pain did not match regarding severity and impact of the total amount of cores taken (p < 0.05). Independent predictors of increased pain at biopsy were prostate volume > 50 ml (p = 0.0179) and expected pain during rectal manipulation (p < 0.001).

Conclusion

Pain during MR-TB can be positively influenced by reducing men’s anxiety, stress and pain expectancy. To meet the needs of the audience, clinicians should address concrete pain levels of each procedural step and consider special treatment for patients with prostate volume > 50 ml and men reporting on increased rectal sensitivity.
Engpässe bei der Verfügbarkeit von ophthalmologischen Medikamenten
Authors: Herwig-Carl M. C. , Loeffler K. U. , Schulze I. , Holz F. G. , Geerling G.
Published: July 2022

Hintergrund

Engpässe bei der medikamentösen Versorgung im ophthalmologischen Bereich nehmen in Deutschland kontinuierlich zu. Bislang wurden diese kaum kommuniziert und diskutiert. In der transparenten Darstellung der Problematik sehen wir den ersten Schritt, damit Konzepte erarbeitet werden können, die dieser Entwicklung gegensteuern.

Ziel der Arbeit

Es erfolgt eine Darstellung der Engpässe bei ophthalmologischen Medikamenten.

Material und Methoden

Es erfolgen eine Auflistung und Diskussion der uns bekannten Engpässe in der medikamentösen Versorgung.

Ergebnisse

Wir unterscheiden die Engpässe in (1) Lieferengpässe, (2) Einstellung der Produktion, (3) fehlende Verfügbarkeit in Deutschland, (4) Herstellung von Medikamenten in spezialisierten Apotheken bei oft fehlender Zulassung für die ophthalmologische Indikation.

Diskussion

Die Gründe für die Medikamentenversorgung in der Augenheilkunde sind vielschichtig, und dementsprechend sind auch keine einfachen Lösungen zu erwarten. Industrie und ordnungspolitische Instanzen auf nationaler und europäischer Ebene sind jedoch aufgefordert, hier gemeinsam mit den ophthalmologischen Gesellschaften die zugrunde liegenden Probleme zu analysieren und entsprechende Lösungswege zu finden.
On the Influences of Urbanization on the Extreme Rainfall over Zhengzhou on 20 July 2021: A Convection-Permitting Ensemble Modeling Study
Authors: Luo Yali , Zhang Jiahua , Yu Miao , Liang Xudong , Xia Rudi , Gao Yanyu , Gao Xiaoyu , Yin Jinfang
Published: July 2022

This study investigates the influences of urban land cover on the extreme rainfall event over the Zhengzhou city in central China on 20 July 2021 using the Weather Research and Forecasting model at a convection-permitting scale [1-km resolution in the innermost domain (d3)]. Two ensembles of simulation (CTRL, NURB), each consisting of 11 members with a multi-layer urban canopy model and various combinations of physics schemes, were conducted using different land cover scenarios: (i) the real urban land cover, (ii) all cities in d3 being replaced with natural land cover. The results suggest that CTRL reasonably reproduces the spatiotemporal evolution of rainstorms and the 24-h rainfall accumulation over the key region, although the maximum hourly rainfall is underestimated and displaced to the west or southwest by most members. The ensemble mean 24-h rainfall accumulation over the key region of heavy rainfall is reduced by 13%, and the maximum hourly rainfall simulated by each member is reduced by 15–70 mm in CTRL relative to NURB. The reduction in the simulated rainfall by urbanization is closely associated with numerous cities/towns to the south, southeast, and east of Zhengzhou. Their heating effects jointly lead to formation of anomalous upward motions in and above the planetary boundary layer (PBL), which exaggerates the PBL drying effect due to reduced evapotranspiration and also enhances the wind stilling effect due to increased surface friction in urban areas. As a result, the lateral inflows of moisture and high-θe (equivalent potential temperature) air from south and east to Zhengzhou are reduced.
An object-based climatology of precipitation systems in Sydney, Australia
Authors: Ayat Hooman , Evans Jason P. , Sherwood Steven C. , Soderholm Joshua
Published: July 2022

The climate is warming and this is changing some aspects of storms, but we have relatively little knowledge of storm characteristics beyond intensity, which limits our understanding of storms overall. In this study, we apply a cell-tracking algorithm to 20 years of radar data at a mid-latitude coastal-site (Sydney, Australia), to establish a regional precipitation system climatology. The results show that extreme storms in terms of translation-speed, size and rainfall intensity usually occur in the warm season, and are slower and more intense over land between ~ 10 am and ~ 8 pm (AEST), peaking in the afternoon. Precipitation systems are more frequent in the cold season and often initiate over the ocean and move northward, leading to precipitation mostly over the ocean. Using clustering algorithms, we have found five precipitation system types with distinct properties, occurring throughout the year but peaking in different seasons. While overall rainfall statistics don't show any link to climate modes, links do appear for some system types using a multivariate approach. This climatology for a variety of precipitation system characteristics will allow future study of any changes in these characteristics due to climate change.
A prediction model for skeletal muscle evaluation and computed tomography-defined sarcopenia diagnosis in a predominantly overweight cohort of patients with head and neck cancer
Authors: Vangelov Belinda , Bauer Judith , Moses Daniel , Smee Robert
Published: July 2022

Purpose

This study investigates the feasibility of computed tomography (CT)-defined sarcopenia assessment using a prediction model for estimating the cross-sectional area (CSA) of skeletal muscle (SM) in CT scans at the third lumbar vertebra (L3), using measures at the third cervical level (C3) in a predominantly overweight population with head and neck cancer (HNC).

Methods

Analysis was conducted on adult patients with newly diagnosed HNC who had a diagnostic positron emission tomography–CT scan. CSA of SM in CT images was measured at L3 and C3 in each patient, and a predictive formula developed using fivefold cross-validation and linear regression modelling. Correlation and agreement between measured CSA at L3 and predicted values were evaluated using intraclass correlation coefficients (ICC) and Bland–Altman plot. The model’s ability to identify sarcopenia was investigated using Cohen’s Kappa (k).

Results

A total of 109 patient scans were analysed, with 64% of the cohort being overweight or obese. The prediction model demonstrated high level of correlation between measured and predicted CSA measures (ICC 0.954, r = 0.916, p < 0.001), and skeletal muscle index (SMI) (ICC 0.939, r = 0.883, p < 0.001). Bland–Altman plot showed good agreement in SMI, with mean difference (bias) = 0.22% (SD 8.65, 95% CI − 3.35 to 3.79%), limits of agreement (− 16.74 to 17.17%). The model had a sensitivity of 80.0% and specificity of 85.0%, with moderate agreement on sarcopenia diagnosis (k = 0.565, p = 0.004).

Conclusion

This model is effective in predicting lumbar SM CSA using measures at C3, and in identifying low SM in a predominately overweight group of patients with HNC.
Fatal blunt chest trauma: an evaluation of rib fracture patterns and age
Authors: O’Donovan Siobhan , van den Heuvel Corinna , Baldock Matthew , Humphries Melissa A. , Byard Roger W.
Published: July 2022

The following study was undertaken to determine if any specific occupant characteristics, crash factors, or associated injuries identified at autopsy could predict the occurrence or number of fractured ribs in adults. Data were accrued from the Traffic Accident Reporting System (TARS) and coronial autopsy reports from Forensic Science SA, Adelaide, South Australia, from January 2000 to December 2020. A total of 1475 motor vehicle fatalities were recorded in TARS between January 2000 and December 2020, and 1082 coronial autopsy reports were identified that corresponded to TARS fatal crash data. After applying exclusion criteria involving missing data, 874 cases were included in the analysis. Of the 874 cases, 685 cases had one or more rib fractures. The leading cause of death for those with rib fractures was multiple trauma (54%), followed by head injury (17%) and chest injuries (10%). The strongest predictor of one or more rib fractures was increasing age (p < 0.001). Other factors found in the regression to be predictive of the number of rib fractures were the presence of a variety of other injuries including thoracic spinal fracture, lower right extremity fracture, splenic injury, liver injury, pelvic fracture, aortic injury, lung laceration, and hemothorax. Age is most likely associated with increasing rib fractures due to reduced tolerance to chest deflection with greater injuries occurring at lower magnitudes of impact. The association of other injuries with rib fractures may be a marker of higher impact severity crashes.
Overnight sleeping heart rate variability of Army recruits during a 12-week basic military training course
Authors: Macartney Michael J. , Larsen Penelope , Gibson Neil , Michael Scott , Drain Jace , Peoples Gregory E. , Groeller Herbert
Published: July 2022

Purpose

This study aimed to quantify sleeping heart rate (HR) and HR variability (HRV) alongside circulating tumor necrosis factor alpha (TNFα) concentrations during 12-week Basic Military Training (BMT). We hypothesised that, despite a high allostatic load, BMT would increase cardiorespiratory fitness and HRV, while lowering both sleeping HR and TNFα in young healthy recruits.

Methods

Sixty-three recruits (18–43 years) undertook ≥ 2 overnight cardiac frequency recordings in weeks 1, 8 and 12 of BMT with 4 h of beat-to-beat HR collected between 00:00 and 06:00 h on each night. Beat-to-beat data were used to derive HR and HRV metrics which were analysed as weekly averages (totalling 8 h). A fasted morning blood sample was collected in the equivalent weeks for the measurement of circulating TNFα concentrations and predicted VO2max was assessed in weeks 2 and 8.

Results

Predicted VO2max was significantly increased at week 8 (+ 3.3 ± 2.6 mL kg−1 min−1; p < 0.001). Sleeping HR (wk1, 63 ± 7 b min−1) was progressively reduced throughout BMT (wk8, 58 ± 6; wk12, 55 ± 6 b min−1; p < 0.01). Sleeping HRV reflected by the root mean square of successive differences (RMSSD; wk1, 86 ± 50 ms) was progressively increased (wk8, 98 ± 50; wk12, 106 ± 52 ms; p < 0.01). Fasted circulating TNFα (wk1, 9.1 ± 2.8 pg/mL) remained unchanged at wk8 (8.9 ± 2.5 pg/mL; p = 0.79) but were significantly reduced at wk12 (8.0 ± 2.4 pg/mL; p < 0.01).

Conclusion

Increased predicted VO2max, HRV and reduced HR during overnight sleep are reflective of typical cardiorespiratory endurance training responses. These results indicate that recruits are achieving cardiovascular health benefits despite the high allostatic load associated with the 12-week BMT.
Pacifier use and breastfeeding in term and preterm newborns—a systematic review and meta-analysis
Authors: Tolppola Olli , Renko Marjo , Sankilampi Ulla , Kiviranta Panu , Hintikka Leena , Kuitunen Ilari
Published: July 2022

The purpose of this study is to assess whether pacifier use is associated with breastfeeding success in term and preterm newborns and whether it influences hospitalization time in preterm newborns. Four databases were searched for randomized controlled trials (RCTs), and a systematic review and meta-analysis were conducted. The risk of bias and evidence quality, according to the GRADE methodology, were analyzed. Risk ratios with 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) for continuous outcomes were used. The random effect model was used if heterogeneity was high (I2 over 40%). We screened 772 abstracts, assessed 44 full texts, and included 10 studies, of which 5 focused on term and 5 on preterm newborns. There were a few concerns about the risk of bias in 9 of the 10 studies. Breastfeeding rates were analyzed at 2, 3, 4, and 6 months, and the success rates were similar between the restricted and free pacifier use groups (evidence quality was moderate to high). In preterm neonates, the use of a pacifier shortened the duration of hospitalization by 7 days (MD 7.23, CI 3.98–10.48) and the time from gavage to total oral feeding by more than 3 days (MD 3.21 days, CI 1.19–5.24) (evidence quality was ranked as moderate).

   Conclusions: Based on our meta-analysis, pacifier use should not be restricted in term newborns, as it is not associated with lower breastfeeding success rates. Furthermore, introducing pacifiers to preterm newborns should be considered, as it seems to shorten the time to discharge as well as the transition time from gavage to total oral feeding.

What is Known:• Observational studies show that infants who use a pacifier are weaned from breastfeeding earlier.• Previous randomized studies have not presented such results, and there have been no differences in the successful breastfeeding rates regardless of the use of pacifier.

What is New:• Term and preterm newborns do not have worse breastfeeding outcomes if a pacifier is introduced to them, and additionally preterm newborns have shorter hospitalization times.• The decision to offer a pacifier should depend on the caregivers instead of hospital policy or staff recommendation, as there is no evidence to support the prohibition or restriction.
A functional enhancement on scarred fingerprint using sigmoid filtering
Authors: Kolivand Hoshang , Hamid Ainul Azura Binti Abdul , Asadianfam Shiva , Rahim Mohd Shafry Mohd
Published: July 2022

Fingerprint has been widely used in biometric applications. Numerous established researches on image enhancement techniques have been done to improve the quality of fingerprint images. However, the production of low-quality images due to the presence of scars remains a challenge in biometrics. The scars damage the fingerprint minutiae information due to broken ridges and they reduce the accuracy of identification. This research developed an image enhancement approach to improve the quality of scarred fingerprint images to generate accurate minutiae extraction. To achieve the aim, the scarred image was improved by removing noise using a new filter, Median Sigmoid (MS), and the corrected ridges were reconstructed using ridges structure enhancement algorithm. This was done to enhance the broken ridges structure. MS filter is a combination of median filter and modified sigmoid function that improves the image contrast and simultaneously removes noise in the fingerprint image. Following that, the filtered image was used in the ridges structure enhancement process. To identify true minutiae, the broken ridges structure in the filtered image needed to be accurately verified. In the ridges structure reconstruction process, an algorithm was enhanced to identify the best value of Sigma parameter (σ) used in the Gaussian Low-pass filter to generate a better orientation image. The image is important to reconstruct the corrupted fingerprint ridges structure. The evaluation for the proposed approach used the National Institute of Standards and Technology Special Database 14, and the results showed a 37% improvement of the quality index in comparison to approaches found in related research. The findings of the evaluation showed that the proposed enhancement approach produced a better minutiae extraction result and this is very significant in the field of fingerprint image enhancement.
Types of spectroscopy and microscopy techniques for cancer diagnosis: a review
Authors: Kaniyala Melanthota Sindhoora , Kistenev Yury V. , Borisova Ekaterina , Ivanov Deyan , Zakharova Olga , Boyko Andrey , Vrazhnov Denis , Gopal Dharshini , Chakrabarti Shweta , K Shama Prasada , Mazumder Nirmal
Published: July 2022

Cancer is a life-threatening disease that has claimed the lives of many people worldwide. With the current diagnostic methods, it is hard to determine cancer at an early stage, due to its versatile nature and lack of genomic biomarkers. The rapid development of biophotonics has emerged as a potential tool in cancer detection and diagnosis. Using the fluorescence, scattering, and absorption characteristics of cells and tissues, it is possible to detect cancer at an early stage. The diagnostic techniques addressed in this review are highly sensitive to the chemical and morphological changes in the cell and tissue during disease progression. These changes alter the fluorescence signal of the cell/tissue and are detected using spectroscopy and microscopy techniques including confocal and two-photon fluorescence (TPF). Further, second harmonic generation (SHG) microscopy reveals the morphological changes that occurred in non-centrosymmetric structures in the tissue, such as collagen. Again, Raman spectroscopy is a non-destructive method that provides a fingerprinting technique to differentiate benign and malignant tissue based on Raman signal. Photoacoustic microscopy and spectroscopy of tissue allow molecule-specific detection with high spatial resolution and penetration depth. In addition, terahertz spectroscopic studies reveal the variation of tissue water content during disease progression. In this review, we address the applications of spectroscopic and microscopic techniques for cancer detection based on the optical properties of the tissue. The discussed state-of-the-art techniques successfully determines malignancy to its rapid diagnosis.
The effect of smoking on survival in lung carcinoma patients with brain metastasis: a systematic review and meta-analysis
Authors: Chawla Shreya , Tewarie Ishaan A. , Zhang Qingwei O. , Hulsbergen Alexander F. C. , Mekary Rania A. , Broekman Marike L. D.
Published: July 2022

The effects of smoking on survival in BM patients have yet to be reviewed and meta-analysed. However, previous studies have shown that smokers had a greater risk of dying from lung cancer compared to non-smokers. This meta-analysis, therefore, aimed to analyse the effects of cigarette smoking on overall survival (OS) and progression-free survival (PFS) in lung cancer BM patients. PubMed, Embase, Web of Science, Cochrane and Google Scholar were searched for comparative studies regarding the effects of smoking on incidence and survival in brain metastases patients up to December 2020. Three independent reviewers extracted overall survival (OS) and progression-free survival data (PFS). Random-effects models were used to pool multivariate-adjusted hazard ratios (HR). Out of 1890 studies, fifteen studies with a total of 2915 patients met our inclusion criteria. Amongst lung carcinoma BM patients, those who were smokers (ever or yes) had a worse overall survival (HR: 1.34, 95% CI 1.13, 1.60, I2: 72.1%, p-heterogeneity < 0.001) than those who were non-smokers (never or no). A subgroup analysis showed the association to remain significant in the ever/never subgroup (HR: 1.34, 95% CI 1.11, 1.63) but not in the yes/no smoking subgroup (HR: 1.30, 95% CI 0.44, 3.88). This difference between the two subgroups was not statistically significant (p = 0.91). Amongst lung carcinoma BM patients, smoking was associated with a worse OS and PFS. Future studies examining BMs should report survival data stratified by uniform smoking status definitions.
“Peas in a pod”: Oral History Reflections on Autistic Identity in Family and Community by Late-Diagnosed Adults
Authors: Lilley Rozanna , Lawson Wenn , Hall Gabrielle , Mahony Joanne , Clapham Hayley , Heyworth Melanie , Arnold Samuel , Trollor Julian , Yudell Michael , Pellicano Elizabeth
Published: July 2022

In this paper, we report on a participatory oral history study documenting the lives of late-diagnosed autistic adults in Australia. We interviewed 26 autistic adults about their life history and the impact of late diagnosis. All were diagnosed after the age of 35, growing up in an era when autism was not well known. Using reflexive thematic analysis, we uncovered a rich body of reflections on shared Autistic identity and identified three major themes within that data set: ‘conceptualising the Autistic family’, ‘creating Autistic community’, and ‘contesting Autistic identity’. Overall, the study provides insights into the active creation of shared Autistic identity and the importance of Autistic community to these late-diagnosed autistic adults.
Conserving a sustainable urban environment through energy security and project management practices
Authors: Maqbool Rashid , Jowett Emily
Published: July 2022

Construction has been highlighted as one sector that could reduce its effect on the environment by implementing more sustainable methodologies. However, there are many different challenges preventing sustainable construction practice, and despite existing research providing advice for carbon emission reduction, these practices are being somewhat neglected. The purpose of this research is to investigate the challenges surrounding sustainable construction practice and the current knowledge on energy security and project management practices that can aid climate change mitigation. The design methodology of this study involves a thorough literature review of existing knowledge on the subject matter followed by primary research. The survey conducted collected quantitative data of 160 valid responses via an online closed ended questionnaire using snowball sampling methods from the construction and engineering professionals working in the UK construction industry. The study found that most participants agree with the encouragement of sustainable construction practices, but are generally unsure about what they can do. Factors such as government involvement and organisation culture have some significance but will rely on further research in order to assess specific influencing variables. The study contributes to existing research on factors surrounding project management and identifies and plethora of areas of improvement, that can be formed into a holistic approach to the current construction industry practice.
Pharmacological Modulation of Glutamatergic and Neuroinflammatory Pathways in a Lafora Disease Mouse Model
Authors: Mollá Belén , Heredia Miguel , Campos Ángela , Sanz Pascual
Published: July 2022

Lafora disease (LD) is a fatal rare neurodegenerative disorder that affects young adolescents and has no treatment yet. The hallmark of LD is the presence of polyglucosan inclusions (PGs), called Lafora bodies (LBs), in the brain and peripheral tissues. LD is caused by mutations in either EPM2A or EPM2B genes, which, respectively, encode laforin, a glucan phosphatase, and malin, an E3-ubiquitin ligase, with identical clinical features. LD knockout mouse models (Epm2a − / − and Epm2b − / −) recapitulate PG body accumulation, as in the human pathology, and display alterations in glutamatergic transmission and neuroinflammatory pathways in the brain. In this work, we show the results of four pre-clinical trials based on the modulation of glutamatergic transmission (riluzole and memantine) and anti-neuroinflammatory interventions (resveratrol and minocycline) as therapeutical strategies in an Epm2b − / − mouse model. Drugs were administered in mice from 3 to 5 months of age, corresponding to early stage of the disease, and we evaluated the beneficial effect of the drugs by in vivo behavioral phenotyping and ex vivo histopathological brain analyses. The behavioral assessment was based on a battery of anxiety, cognitive, and neurodegenerative tests and the histopathological analyses included a panel of markers regarding PG accumulation, astrogliosis, and microgliosis. Overall, the outcome of ameliorating the excessive glutamatergic neurotransmission present in Epm2b − / − mice by memantine displayed therapeutic effectiveness at the behavioral levels. Modulation of neuroinflammation by resveratrol and minocycline also showed beneficial effects at the behavioral level. Therefore, our study suggests that both therapeutical strategies could be beneficial for the treatment of LD patients.

Graphical abstract

A mouse model of Lafora disease (Epm2b-/-) was used to check the putative beneficial effect of different drugs aimed to ameliorate the alterations in glutamatergic transmission and/or neuroinflammation present in the model. Drugs in blue gave a more positive outcome than the rest.
The effectivity of targeted therapy and immunotherapy in patients with advanced metastatic and non-metastatic cancer of the esophagus and esophago-gastric junction
Authors: Valkema M. J. , Mostert B. , Lagarde S. M. , Wijnhoven B. P. L. , van Lanschot J. J. B.
Published: July 2022

Therapies that target specific tumor drivers or immune checkpoints are increasingly explored for esophageal cancer patients. This review addresses developments in therapies with targeted anti-human epidermal growth factor receptor 2 (HER2) agents and immune checkpoint inhibitors in patients with stage IV esophageal cancer. First-line palliative treatment with the anti-HER2 agent trastuzumab in combination with chemotherapy has been approved for use in patients with HER2 positive gastro-esophageal adenocarcinoma. Neoadjuvant chemoradiotherapy plus perioperative trastuzumab however has not demonstrated a survival benefit in advanced esophageal cancer patients eligible for surgery. Potentially better responses are expected with dual agent anti-HER2 therapy instead of monotherapy. In the metastatic setting, the antibody–drug conjugate trastuzumab deruxtecan is effective after progression on trastuzumab. Nivolumab and pembrolizumab, antibodies blocking the programmed cell death 1 (PD-1) receptor on T cells, have recently gained approval for clinical use in esophageal cancer patients for specific indications. Synergistic effects might be achieved with combinations of immune checkpoint inhibitors that target PD-1 on T cells or PD ligand 1 (PD-L1) on tumor cells and anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) receptor on T cells. Multiple clinical trials investigating combinations of targeted and immunotherapies, with or without (neo)adjuvant chemo(radio)therapy, for curative and palliative treatment, are underway, and are expected to deliver a long-awaited improvement in the prognosis of esophageal cancer patients.
VHL and DNA damage repair pathway alterations as potential clinical biomarkers for first-line TKIs in metastatic clear cell renal cell carcinomas
Authors: Zhou Jiale , Wang Junyun , Kong Wen , Zhang Jin , Wu Xiaorong , Huang Jiwei , Zheng Junhua , Chen Yonghui , Zhai Wei , Xue Wei
Published: July 2022

Purpose

Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) are being used for the first-line treatment of metastatic clear cell renal cell carcinoma (mccRCC). Here, we set out to explore associations between genomic statuses, gene expression clusters and clinical outcomes of mccRCCs upon the application of VEGFR-TKIs.

Methods

A retrospective study of 56 patients with mccRCC who received first-line VEGFR-TKIs and who underwent genomic profiling and whole transcriptome sequencing was conducted. Survival analysis was carried out using log-rank tests and Cox regression analyses, and Kaplan–Meier curves were plotted. Clustering was performed using the K-means method.

Results

Among the 56 patients tested, 17 harbored DNA Damage and Repair (DDR) pathway alterations and 35 VHL mutations. The median progression-free survival (PFS) rates for the DDR and VHL alteration groups were 18 and 18 months, respectively, compared with 14 and 10 months for the nonmutant groups. DDR mutations, VHL mutations and co-mutations were identified as prognostic biomarkers of a longer PFS (p = 0.017, 0.04, 0.014). K-means clustering of expressed transcripts revealed three clusters of 40 patients: C_1, C_2 and C_3. The C_1 cluster exhibited the best PFS and objective response rate (ORR) to TKI therapy, with the highest proportion of DDR and VHL mutations. Further analysis of the tumor immune environment revealed that the C_1 cluster was enriched in activated CD8 T cells and effector CD4 T cells, whereas the C_2 cluster was enriched in eosinophils, mast cells and DC cells and, thus, in immunosuppressive cells.

Conclusions

We found that patients with mccRCC harboring DDR and VHL alterations were more likely to benefit from first-line VEGF-TKI systemic therapy than patients with wild-type disease. In addition, we found that a three-cluster prognostic model based on gene expression can predict PFS and ORR, which was well-matched with activated TIL infiltration.
Hydrogen Sulfide Modulates Salinity Stress in Common Bean Plants by Maintaining Osmolytes and Regulating Nitric Oxide Levels and Antioxidant Enzyme Expression
Authors: Dawood Mona F. A. , Sofy Mahmoud R. , Mohamed Heba I. , Sofy Ahmed R. , Abdel-kader Huwida A. A.
Published: July 2022

The purpose of the present study is to investigate the role of hydrogen sulfide (H2S), in improving resistance to common bean salt stress. Method shows that common bean seeds were soaked in water and in two concentrations of sodium hydrosulfide (50 and 100 µM) for 8 h. After 25 days from sowing, the pots were irrigated with water and with two concentrations of NaCl (75 and 150 mM) until the end of the experiment. Results revealed that H2S relieved salt stress by decreasing growth inhibition and photosynthetic characteristics, and increasing osmolyte contents (proline and glycine betaine). Furthermore, H2S reduced oxidative damage by lowering lipid peroxidation, electrolyte leakage, and reactive oxygen species production such as hydrogen peroxide, hydroxyl radicals, and superoxide anion by increasing non-enzymatic antioxidants such as ascorbic acid and glutathione, as well as enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT), peroxidase (POX), ascorbate peroxidase (APX), glutathione reductase (GR), and nitrate reductase (NR). Meanwhile, salt stress and H2S application increased the endogenous level of H2S, which was accompanied by an increase in nitric oxide concentration. H2S, in particular, maintained sodium (Na+) and potassium (K+) homeostasis in the presence of excess NaCl. In general, H2S effectively reduced oxidative stress in common bean plants by increasing relative expression levels of copper-zinc superoxide dismutase (Cu-ZnSOD), CAT, and glutathione S-transferase (GST). Applying H2S to common bean plants could protect them from salinity stress by maintaining the Na+/K+ balance, boosting endogenous H2S and nitric oxide levels, and preventing oxidative damage by increasing antioxidant activity.