bluuebunny/crossref_metadata_2025 huggingface dataset:
Large-scale validation of the Prediction model Risk Of Bias ASsessment Tool (PROBAST) using a short form: high risk of bias models show poorer discrimination
Authors: Venema Esmee , Wessler Benjamin S , Paulus Jessica K , Salah Rehab , Raman Gowri , Leung Lester Y , Koethe Benjamin C , Nelson Jason , Park Jinny G , van Klaveren David , Steyerberg Ewout W , Kent David M
Published: January 2021

Objective

To assess whether the Prediction model Risk Of Bias ASsessment Tool (PROBAST) and a shorter version of this tool can identify clinical prediction models (CPMs) that perform poorly at external validation.

Study Design and Setting

We evaluated risk of bias (ROB) on 102 CPMs from the Tufts CPM Registry, comparing PROBAST to a short form consisting of six PROBAST items anticipated to best identify high ROB. We then applied the short form to all CPMs in the Registry with at least 1 validation and assessed the change in discrimination (dAUC) between the derivation and the validation cohorts (n=1,147).

Results

PROBAST classified 98/102 CPMS as high ROB. The short form identified 96 of these 98 as high ROB (98% sensitivity), with perfect specificity. In the full CPM registry, 529/556 CPMs (95%) were classified as high ROB, 20 (4%) low ROB, and 7 (1%) unclear ROB. Median change in discrimination was significantly smaller in low ROB models (dAUC −0.9%, IQR −6.2%–4.2%) compared to high ROB models (dAUC −11.7%, IQR −33.3%–2.6%; p<0.001).

Conclusion

High ROB is pervasive among published CPMs. It is associated with poor performance at validation, supporting the application of PROBAST or a shorter version in CPM reviews.

What is new

High risk of bias is pervasive among published clinical prediction models

High risk of bias identified with PROBAST is associated with poorer model performance at validation

A subset of questions can distinguish between models with high and low risk of bias
Mechanisms of lactic acid gustatory attraction inDrosophila
Authors: Stanley Molly , Ghosh Britya , Weiss Zachary F. , Christiaanse Jaime , Gordon Michael D.
Published: January 2021

Sour has been studied almost exclusively as an aversive taste modality. Yet, recent work inDrosophilademonstrates that specific carboxylic acids are attractive at ecologically relevant concentrations. Here, we demonstrate that lactic acid is an appetitive and energetic tastant, which stimulates feeding through activation of sweet gustatory receptor neurons (GRNs). This activation displays distinct, mechanistically separable, stimulus onset and removal phases. Ionotropic receptor 25a (IR25a) primarily mediates the onset response, which shows specificity for the lactate anion and drives feeding initiation. Conversely, sweet gustatory receptors (Gr64a-f) mediate a non-specific removal response to low pH that primarily impacts ingestion. While mutations in either receptor family have marginal impacts on feeding, lactic acid attraction is completely abolished in combined mutants. Thus, specific components of lactic acid are detected through two classes of receptors to activate a single set of sensory neurons in physiologically distinct ways, ultimately leading to robust behavioural attraction.
Secreted reporter assay enables quantitative and longitudinal monitoring of neuronal activity
Authors: Santos Ana C. , Park Sungjin
Published: January 2021

The ability to measure changes in neuronal activity in a quantifiable and precise manner is of fundamental importance to understand neuron development and function. Repeated monitoring of neuronal activity of the same population of neurons over several days is challenging and, typically, low-throughput. Here, we describe a new biochemical reporter assay that allows for repeated measurements of neuronal activity in a cell type-specific manner. We coupled activity-dependent elements from theArc/Arg3.1gene with a secreted reporter,Gaussialuciferase, to quantify neuronal activity without sacrificing the neurons. The reporter predominantly senses calcium and NMDA receptor-dependent activity. By repeatedly measuring the accumulation of the reporter in cell media, we can profile the developmental dynamics of neuronal activity in cultured neurons from male and female mice. The assay also allows for longitudinal analysis of pharmacological treatments, thus distinguishing acute from delayed responses. Moreover, conditional expression of the reporter allows for monitoring cell type-specific changes. This simple, quantitative, cost-effective, automatable, and cell type-specific activity reporter is a valuable tool to study the development of neuronal activity in normal and disease-model conditions, and to identify small molecules or protein factors that selectively modulate the activity of a specific population of neurons.

Significance

Neurological and neurodevelopmental disorders are prevalent worldwide. Despite significant advances in our understanding of synapse formation and function, developing effective therapeutics remains challenging, in part due to the lack of simple and robust high-throughput screening assays of neuronal activity. Here, we describe a simple biochemical assay that allows for repeated measurements of neuronal activity in a cell type-specific manner. Thus filling the need for assays amenable to longitudinal studies, such as those related to neural development. Other advantages include its simple and quantitative nature, logitudinal profiling, cell type-specificity, and being multiplexed with other invasive techniques.
Spinal V1 neurons inhibit motor targets locally and sensory targets distally to coordinate locomotion
Authors: Sengupta Mohini , Daliparthi Vamsi , Roussel Yann , Bui Tuan Vu , Bagnall Martha W.
Published: January 2021

Rostro-caudal coordination of spinal motor output is essential for locomotion. Most spinal interneurons project axons longitudinally to govern locomotor output, yet their connectivity along this axis remains unclear. In this study, we use larval zebrafish to map synaptic outputs of a major inhibitory population, V1 (Eng1+) neurons, which are implicated in dual sensory and motor functions. We find that V1 neurons exhibit long axons extending rostrally and exclusively ipsilaterally for an average of 6 spinal segments; however, they do not connect uniformly with their post-synaptic targets along the entire length of their axon. Locally, V1 neurons inhibit motor neurons (both fast and slow) and other premotor targets including V2a, V2b and commissural pre-motor neurons. In contrast, V1 neurons make robust inhibitory contacts throughout the rostral extent of their axonal projections onto a dorsal horn sensory population, the Commissural Primary Ascending neurons (CoPAs). In a computational model of the ipsilateral spinal network, we show that this pattern of short range V1 inhibition to motor and premotor neurons is crucial for coordinated rostro-caudal propagation of the locomotor wave. We conclude that spinal network architecture in the longitudinal axis can vary dramatically, with differentially targeted local and distal connections, yielding important consequences for function.
An effect of the COVID-19 pandemic: significantly more complicated appendicitis due to delayed presentation of patients!
Authors: Burgard Marie , Cherbanyk Floryn , Nassiopoulos Konstantinos , Malekzadeh Sonaz , Pugin François , Egger Bernhard
Published: January 2021

AIMS OF THE STUDY

The novel coronavirus pandemic has affected emergency department consultations for surgical pathologies. The aim of our study was to compare the number of acute appendicitis cases and the proportion of complicated appendicitis before and during the COVID-19 pandemic.

METHODS

We retrospectively analyzed all data collected from a multi-center database of patients presenting to the emergency department for acute appendicitis during the COVID-19 pandemic from March 12 to June 6, 2020, and compared these data with those from the same periods in 2017, 2018, and 2019. The number of acute appendicitis cases, proportion of complicated appendicitis, and pre- and postoperative patient characteristics were evaluated.

RESULTS

A total of 306 patients were included in this evaluation. Sixty-five patients presented during the 2020 COVID-19 pandemic lockdown (group A), and 241 patients in previous years (group B: 2017–2019). The number of consultations for acute appendicitis decreased by almost 20 percent during the pandemic compared with previous periods, with a significant increase in complicated appendicitis (52% in group A versus 20% in group B, p < 0,001.). Comparing the two groups, significant differences were also noted in the duration of symptoms (symptoms > 48h in 61% and 26%, p < 0,001), the intervention time (77 vs 61 minutes, p = 0,002), length of hospital stay (hospitalization of > 2 days in 63% and 32%, p < 0.001) and duration of antibiotic treatment (antibiotics > 3 days in 36% and 24% p = 0.001).

CONCLUSIONS

The COVID-19 pandemic resulted in a decreased number of consultations for acute appendicitis, with a higher proportion of complicated appendicitis, most likely due to patient delay in consulting the emergency department at symptom onset. Patients and general practitioners should be aware of this problem to avoid a time delay from initial symptoms to consultation.
The CPEB3 ribozyme modulates hippocampal-dependent memory
Authors: Chen Claire C. , Han Joseph , Chinn Carlene A. , Li Xiang , Nikan Mehran , Myszka Marie , Tong Liqi , Bredy Timothy W. , Wood Marcelo A. , Lupták Andrej
Published: January 2021

A self-cleaving ribozyme mapping to an intron of the cytoplasmic polyadenylation element binding protein 3 (CPEB3) gene has been suggested to play a role in human episodic memory, but the underlying mechanisms mediating this effect are not known. The ribozyme’s self-scission half-life matches the time it takes an RNA polymerase to reach the immediate downstream exon, suggesting that the ribozyme-dependent intron cleavage is tuned to co-transcriptional splicing of theCPEB3mRNA. Here we report that the murine ribozyme modulates its own host mRNA maturation in both cultured cortical neurons and the hippocampus. Inhibition of the ribozyme using an antisense oligonucleotide leads to increased CPEB3 protein expression, which enhances polyadenylation and translation of localized plasticity-related target mRNAs, and subsequently strengthens hippocampal-dependent long-term memory. These findings reveal a previously unknown role for self-cleaving ribozyme activity in regulating experience-induced co-transcriptional and local translational processes required for learning and memory.
Existence of SARS-CoV-2 RNA on ambient particulate matter samples: A nationwide study in Turkey
Authors: Kayalar Özgecan , Arı Akif , Babuççu Gizem , Konyalılar Nur , Doğan Özlem , Can Füsun , Şahin Ülkü A. , Gaga Eftade O. , Kuzu S. Levent , Arı Pelin E. , Odabası Mustafa , Taşdemir Yücel , Cindoruk S.Sıddık , Esen Fatma , Sakın Egemen , Çalışkan Burak , Tecer Lokman H. , Fıçıcı Merve , Altın Ahmet , Onat Burcu , Ayvaz Coşkun , Uzun Burcu , Saral Arslan , Döğeroğlu Tuncay , Malkoç Semra , Üzmez Özlem Ö. , Kunt Fatma , Aydın Senar , Kara Melik , Yaman Barış , Doğan Güray , Olgun Bihter , Dokumacı Ebru N. , Güllü Gülen , Uzunpınar Elif S. , Bayram Hasan
Published: January 2021

Coronavirus disease 2019 (COVID-19) is caused by the SARS-CoV-2 virus and has been affecting the world since the end of 2019. Turkey is severely affected with the first case being reported on March 11th 2020. Ambient particulate matter (PM) samples in various size ranges were collected from 13 sites including urban and urban background locations and hospital gardens in 10 cities across Turkey between the 13th of May and the 14th of June, 2020 to investigate a possible presence of SARS-CoV-2 RNA on ambient PM. A total of 155 daily samples (TSP, n=80; PM2.5, n=33; PM2.5-10, n=23; PM10, n=19; and 6 size segregated, n=48) were collected using various samplers in each city. The N1 gene and RdRP gene expressions were analyzed for the presence of SARS-CoV-2 as suggested by the Centers for Disease Control and Prevention (CDC). According to RT-PCR and 3D-RT-PCR analysis, dual RdRP and N1 gene positivity were detected in 20 (9.8 %) of the samples. The highest percentage of virus detection on PM samples was from hospital gardens in Tekirdağ, Zonguldak, and İstanbul—especially in PM2.5 mode. Samples collected from two urban sites were also positive. Findings of this study have suggested that SARS-CoV-2 may be transported by ambient particles especially at sites close to the infection hot-spots. However, whether this has an impact on the spread of the virus infection remains to be determined.

Significance Statement

Although there are several studies reporting the existence of SARS-CoV-2 in indoor aerosols is established, it remains unclear whether the virus is transported by ambient atmospheric particles. The presence of the SARS-CoV-2 RNA in ambient particles collected from characteristic sites within various size ranges was investigated, and positive results were found in urban sites especially around Turkish hospitals. In this context, this study offers a new discussion on the transmission of the virus via ambient particles.
A Novel Swine Model of the Acute Respiratory Distress Syndrome Using Clinically-Relevant Injury Exposures
Authors: Tiba Mohamad Hakam , McCracken Brendan M. , Leander Danielle C. , Colmenero Carmen I. , Nemzek Jean A. , Sjoding Michael W. , Konopka Kristine E. , Flott Thomas L. , VanEpps J. Scott , Daniels Rodney , Ward Kevin R. , Stringer Kathleen A. , Dickson Robert P.
Published: January 2021

To date, existing animal models of the acute respiratory distress syndrome (ARDS) have failed to translate preclinical discoveries into effective pharmacotherapy or diagnostic biomarkers. To address this translational gap, we developed a high-fidelity swine model of ARDS utilizing clinically-relevant lung injury exposures. Fourteen male swine were anesthetized, mechanically ventilated, and surgically instrumented for hemodynamic monitoring, blood, and tissue sampling. Animals were allocated to one of three groups: 1)Indirect lung injury only: animals were inoculated by direct injection ofE. coliinto the kidney parenchyma, provoking systemic inflammation and distributive shock physiology; 2)Direct lung injury only: animals received volutrauma, hyperoxia, and bronchoscope-delivered gastric particles; 3)Combined indirect and direct lung injury:animals were administered both above-described indirect and direct lung injury exposures. Animals were monitored for up to 12 hours, with serial collection of physiologic data, blood samples, and radiographic imaging. Lung tissue was acquired post-mortem for pathological examination. In contrast toindirect lung injury onlyanddirect lung injury onlygroups, animals in thecombined indirect and direct lung injurygroup exhibited all of the physiological, radiographic, and histopathologic hallmarks of human ARDS: impaired gas exchange (mean PaO2/FiO2ratio 124.8 ± 63.8), diffuse bilateral opacities on chest radiographs, and extensive pathologic evidence of diffuse alveolar damage. Our novel porcine model of ARDS, built on clinically-relevant lung injury exposures, faithfully recapitulates the physiologic, radiographic, and histopathologic features of human ARDS, and fills a crucial gap in the translational study of human lung injury.
Comprehensive stratum corneum ceramide profiling reveals reduced acylceramides in ichthyosis patient with CERS3 mutations
Authors: Yamamoto Moe , Sassa Takayuki , Kyono Yuki , Uemura Hiroyasu , Kugo Masaaki , Hayashi Hideki , Imai Yasutomo , Yamanishi Kiyofumi , Kihara Akio
Published: January 2021

The stratum corneum (SC) of the epidermis acts as a skin permeability barrier, and abnormalities in SC formation lead to several skin disorders. Lipids, especially the epidermis‐specific ceramide classes ω‐O‐acylceramides (acylceramides) and protein‐bound ceramides, are essential for skin barrier formation. Ceramide synthase 3 (CERS3) is involved in the synthesis of acylceramides and protein‐bound ceramides, and CERS3 mutations cause autosomal recessive congenital ichthyosis. In the present study, we measured ceramide synthase activity and performed comprehensive SC ceramide profiling in an ichthyosis patient with compound heterozygous CERS3 mutations: nonsense mutation p.Arg75* and missense mutation p.Arg229His. The activity of p.Arg75* and p.Arg229His mutant CERS3 proteins was reduced to 4% and 56%, respectively, of the wild‐type protein. In the patient’s SC, acylceramide levels were greatly reduced, but the levels of protein‐bound ceramides remained almost unchanged. Non‐acylated ceramide levels were also affected in the patient; in particular, the levels of ceramides composed of sphingosine and non‐hydroxy or α‐hydroxy fatty acid were substantially higher than in healthy controls. These results suggest that a reduction in acylceramide levels alone leads to ichthyosis. Although protein‐bound ceramides are synthesized from acylceramides, levels of acylceramides and protein‐bound ceramides are not necessarily correlated.
Does Voice Benefit or Harm Occupational Well‐Being? The Role of Job Insecurity
Authors: Röllmann Laura Frederike , Weiss Mona , Zacher Hannes
Published: January 2021

Although employee voice is integral for organizational functioning, it is not well understood how voice affects occupational well‐being, particularly when jobs are perceived as insecure. Drawing from the dual‐pathway model of proactivity, which is based on self‐determination and conservation of resources theories, we integrate theorizing on the well‐being consequences of voice with the job insecurity literature. First, we hypothesize that voice leads to increases in both vigour and fatigue. Second, we propose that job insecurity moderates these effects, such that the effect of voice on increases in vigour is stronger (weaker) when job insecurity is low (high), whereas the effect of voice on increases in fatigue is stronger (weaker) when job insecurity is high (low). Seven hundred and thirty three full‐time employees in Germany participated in two surveys, three months apart. Results largely supported our predictions and showed that voice led to increases in vigour. Moreover, voice predicted increases (decreases) in fatigue when job insecurity was high (low). However, voice and job insecurity did not interact in predicting changes in vigour. Reverse causal analyses showed no effects of vigour and fatigue on changes in voice. Our discussion focuses on why and how perceptions of employment relations should be considered to determine well‐being consequences of voice.
Radiological perspective of COVID‐19 pneumonia: The early features and progressive behaviour on high‐resolution CT
Authors: Tsujikawa Tetsuya , Umeda Yukihiro , Itoh Harumi , Sakai Toyohiko , Iwasaki Hiromichi , Okazawa Hidehiko , Ishizuka Tamotsu , Kimura Hirohiko
Published: January 2021

Since the outbreak of Coronavirus disease 2019 (COVID‐19) in China, many researchers have reported the chest CT manifestations of COVID‐19 pneumonia. High‐resolution CT (HRCT) of the lung can provide important clues to understand the progressive behaviour of COVID‐19 pneumonia. This pictorial essay discusses the early features and potential progressive behaviour of COVID‐19 on HRCT of the lung.
Emergency physician stressors, concerns, and behavioral changes during COVID‐19: A longitudinal study
Authors: Baumann Brigitte M. , Cooper Richelle J. , Medak Anthony J. , Lim Stephen , Chinnock Brian , Frazier Remi , Roberts Brian W. , Epel Elissa S. , Rodriguez Robert M.
Published: January 2021

Objectives

The objective was to provide a longitudinal assessment of anxiety levels and work and home concerns of U.S. emergency physicians during the COVID‐19 pandemic.

Methods

We performed a longitudinal, cross‐sectional email survey of clinically active emergency physicians (attending, fellow, and resident) at seven academic emergency departments. Follow‐up surveys were sent 4 to 6 weeks after the initial survey and assessed the following: COVID‐19 patient exposure, availability of COVID‐19 testing, levels of home and workplace anxiety/stress, changes in behaviors, and performance on a primary care posttraumatic stress disorder screen (PC‐PTSD‐5). Logistic regression explored factors associated with a high PC‐PTSD‐5 scale score (≥3), indicating increased risk for PTSD.

Results

Of the 426 surveyed initial respondents, 262 (61.5%) completed the follow‐up survey. While 97.3% (255/262) reported treating suspected COVID‐19 patients, most physicians (162/262, 61.8%) had not received testing themselves. In follow‐up, respondents were most concerned about the relaxing of social distancing leading to a second wave (median score = 6, IQR = 4–7). Physicians reported a consistently high ability to order COVID‐19 tests for patients (median score = 6, IQR = 5–7) and access to personal protective equipment (median score = 6, IQR = 5–6). Women physicians were more likely to score ≥ 3 than men on the PC‐PTSD‐5 screener on the initial survey (43.3% vs. 22.5%; Δ 20.8%, 95% confidence interval [CI] = 9.3% to 31.5%), and despite decreases in overall proportions, this discrepancy remained in follow‐up (34.7% vs. 16.8%; Δ 17.9%, 95% CI = 7.1% to 28.1%). In examining the relationship between demographics, living situations, and institution location on having a PC‐PTSD‐5 score ≥ 3, only female sex was associated with a PC‐PTSD‐5 score ≥ 3 (adjusted odds ratio = 2.48, 95% CI = 1.28 to 4.79).

Conclusions

While exposure to suspected COVID‐19 patients was nearly universal, stress levels in emergency physicians decreased with time. At both initial and follow‐up assessments, women were more likely to test positive on the PC‐PTSD‐5 screener compared to men.
Colectomy rates for ulcerative colitis in England 2003‐2016
Authors: Worley Guy , Almoudaris Alex , Bassett Paul , Segal Jonathan , Akbar Ayesha , Ghosh Subrata , Aylin Paul , Faiz Omar
Published: January 2021

Background

Temporal trends in colectomy rate for ulcerative colitis (UC) are particularly relevant in the current era of published IBD standards and changing approach to salvage of acute severe disease.

Aims

To investigate temporal trends in colectomy for UC using English population data.

Methods

The Hospital Episode Statistics (HES) were interrogated between 2003‐2016 with two patient groups investigated independently. An ‘emergency’ cohort: emergency UC admission ≥ three days, age ≥18 and a ‘total population’ cohort: all English patients undergoing colectomy for UC. Mixed methods analyses were utilised.

Results

Emergency cohort: 37 981 patients, 49% female, median age 46. The one‐ and three‐year incidence of colectomy after acute admission was 0.17 and 0.21. Interrupted time series (ITS) analysis suggested reductions in colectomy rate of 4% per year after 2008 at 30 and 90 days following emergency admission, with no significant reduction ≥1 year. Mortality and laparoscopy rates improved when avoiding colectomy at index and emergency admissions; however, the proportion of emergency colectomies after salvage at index admission significantly increased during the study period. Total population cohort: 17 580 patients underwent colectomy for UC between 2003 and 2016, demonstrating a 3.1% annual reduction in total and elective colectomies after 2008, but no reduction in emergency colectomies.

Conclusion

Reductions in short‐term colectomy rates after emergency admission for UC do not persist beyond one year. Emergency colectomy rates remain unchanged. Reduced rates are probably due to multi‐modal improvements in IBD care. A lack of data regarding disease severity precludes further interpretation of appropriate medical salvage and timely surgery.
SGIP1 is involved in regulation of emotionality, mood, and nociception and modulates in vivo signalling of cannabinoid CB1 receptors
Authors: Dvorakova Michaela , Kubik‐Zahorodna Agnieszka , Straiker Alex , Sedlacek Radislav , Hajkova Alena , Mackie Ken , Blahos Jaroslav
Published: January 2021

Background and Purpose

Src homology 3‐domain growth factor receptor‐bound 2‐like endophilin interacting protein 1 (SGIP1) interacts with cannabinoid CB1 receptors. SGIP1 is abundantly and principally expressed within the nervous system. SGIP1 and CB1 receptors co‐localize in axons and presynaptic boutons. SGIP1 interferes with the internalization of activated CB1 receptors in transfected heterologous cells. Consequently, the transient association of CB1 receptors with β‐arrestin2 is enhanced and prolonged, and CB1 receptor‐mediated ERK1/2 signalling is decreased. Because of these actions, SGIP1 may modulate affect, anxiety, pain processing, and other physiological processes controlled by the endocannabinoid system (ECS).

Experimental Approach

Using a battery of behavioural tests, we investigated the consequences of SGIP1 deletion in tasks regulated by the ECS in SGIP1 constitutive knockout (SGIP1−/−) mice.

Key Results

In SGIP1−/− mice, sensorimotor gating, exploratory levels, and working memory are unaltered. SGIP1−/− mice have decreased anxiety‐like behaviours. Fear extinction to tone is facilitated in SGIP1−/− females. Several cannabinoid tetrad behaviours are altered in the absence of SGIP1. SGIP1−/− males exhibit abnormal behaviours on Δ9‐tetrahydrocannabinol withdrawal. SGIP1 deletion also reduces acute nociception, and SGIP1−/− mice are more sensitive to analgesics.

Conclusion and Implications

SGIP1 was detected as a novel protein associated with CB1 receptors, and profoundly modified CB1 receptor signalling. Genetic deletion of SGIP1 particularly affected behavioural tests of mood‐related assessment and the cannabinoid tetrad. SGIP1−/− mice exhibit decreased nociception and augmented responses to CB1 receptor agonists and morphine. These in vivo findings suggest that SGIP1 is a novel modulator of CB1 receptor‐mediated behaviour.
Age‐related differences in morbidity and mortality after surgery for primary clinical T4 and locally recurrent rectal cancer
Authors: Ketelaers S. H. J. , Voogt E. L. K. , Simkens G. A. , Bloemen J. G. , Nieuwenhuijzen G. A. P. , de Hingh I. H. J. , Rutten H. J. T. , Burger J. W. A. , Orsini R. G.
Published: January 2021

Aim

Outcomes in elderly patients (≥75 years) with non‐advanced colorectal cancer have improved. It is unclear whether this is also true for elderly patients with clinical T4 rectal cancer (cT4RC) or locally recurrent rectal cancer (LRRC). We aimed to compare age‐related differences in morbidity and mortality after curative treatment for cT4RC and LRRC.

Methods

All cT4RC and LRRC patients without distant metastasis who underwent curative surgery between 2005 and 2017 in the Catharina Hospital (Eindhoven, The Netherlands) were included. Morbidity and mortality were evaluated based on age (<75 and ≥75 years) and date of surgery (2005–2011 and 2012–2017).

Results

Overall, 72 of 474 (15.2%) cT4RC and 53 of 293 (18.1%) LRRC patients were ≥75 years. No significant differences in the incidence of Clavien–Dindo I–IV complications were observed between age groups. However, in elderly cT4RC patients, cerebrovascular accidents occurred more frequently (4.2% vs. 0.5%, P = 0.03). Between 2005–2011 and 2012–2017, 30‐day mortality improved from 7.5% to 3.1% and from 10.0% to 0.0% in elderly cT4RC and LRRC patients, respectively. The 1‐year mortality during 2012–2017 was worse in elderly than in younger patients (28.1% vs. 6.2%, P = 0.001 for cT4RC and 27.3% vs. 13.8%, P = 0.06 for LRRC). In elderly cT4RC and LRRC patients, 44.4% and 46.2% died due to non‐cancer‐related causes, while only 27.8% and 23.1% died due to disease recurrence, respectively.

Conclusion

Although the 30‐day mortality in elderly cT4RC and LRRC patients improved after curative treatment, the 1‐year mortality in elderly patients continued to be high, which requires more awareness for the elderly after hospitalization.
Medikamenten‐induzierte Photosensibilität: auslösende Medikamente, mögliche Mechanismen und klinische Folgen
Authors: Hofmann Georg Amun , Weber Benedikt
Published: January 2021

Medikamenten‐induzierte Photosensibilität, also phototoxische oder photoallergische Reaktionen durch Pharmazeutika und nachfolgende Exposition gegenüber ultraviolettem oder sichtbarem Licht, ist eine unerwünschte Wirkung, die zunehmend an Interesse gewinnt. Dies zeigt sich am breiten Spektrum aktueller Untersuchungen, die von molekularen Mechanismen und auslösenden Medikamenten über Epidemiologie und Aspekten der öffentlichen Gesundheit bis hin zur langfristigen lichtbedingten Hautalterung und möglichen photokanzerogenen Folgen reichen. Die vorliegende Übersicht fasst den derzeitigen Kenntnisstand mit dem Schwerpunkt auf auslösenden Medikamenten und Langzeitfolgen zusammen. Insgesamt wurde bei 393 verschiedenen Medikamenten oder Inhaltsstoffen ein Potenzial zur Photosensibilisierung beschrieben. Allerdings unterscheiden sich bei diesen Wirkstoffen die Evidenzstufen hinsichtlich der Auslösung von Photosensibilität erheblich. Die betreffenden Pharmazeutika gehören vielen Medikamentenklassen an. Wegen mangelhafter Erfassung und geografischer Unterschiede ist die epidemiologische Bewertung des Risikos durch Photosensibilisatoren schwierig. Dennoch ist aufgrund der breiten Anwendung photosensibilisierender Medikamente in Kombination mit der potenziell photokanzerogenen Wirkung einiger Wirkstoffe von einer bedeutenden Auswirkung auf Gesundheit und Sicherheit auszugehen. Demzufolge ergibt sich ein hoher Bedarf an weiteren Untersuchungen zu den Langzeitfolgen.
A hypothesis for the role of axon demyelination in seizure generation
Authors: de Curtis Marco , Garbelli Rita , Uva Laura
Published: January 2021

Loss of myelin and altered oligodendrocyte distribution in the cerebral cortex are commonly observed both in postsurgical tissue derived from different focal epilepsies (such as focal cortical dysplasias and tuberous sclerosis) and in animal models of focal epilepsy. Moreover, seizures are a frequent symptom in demyelinating diseases, such as multiple sclerosis, and in animal models of demyelination and oligodendrocyte dysfunction. Finally, the excessive activity reported in demyelinated axons may promote hyperexcitability. We hypothesize that the extracellular potassium rise generated during epileptiform activity may be amplified by the presence of axons without appropriate myelin coating and by alterations in oligodendrocyte function. This process could facilitate the triggering of recurrent spontaneous seizures in areas of altered myelination and could result in further demyelination, thus promoting epileptogenesis.
Flow in computer‐mediated environments: A systematic literature review
Authors: Valinatajbahnamiri Mona , Siahtiri Vida
Published: January 2021

Flow has been regarded as an important phenomenon for understanding and delivering compelling experiences to consumers when using computer‐mediated services. Despite the importance of flow in the delivery of computer‐mediated services in computer‐mediated environments, little attention has been devoted to evaluating the status of research and consolidating the findings in the literature. As there is an ongoing debate, concerning the nature of flow, its structure, antecedents and consequences in computer‐mediated environments, the need to understand the literature on flow in these environments becomes more relevant. This study synthesizes the flow literature in computer‐mediated environments by systematically reviewing 137 peer‐reviewed journal articles published across 23 years. We showcase the current state of flow literature and provide (a) general knowledge, (b) methodological and (c) research model structural information of published studies (structure, antecedents and consequences of flow). The review concludes with identification of current gaps, future research directions and their managerial implications in computer‐mediated environments.
Predictive factors of anxiety and depression among nurses fighting coronavirus disease 2019 in China
Authors: Pang Yongli , Fang Hengying , Li Lili , Chen Minhua , Chen Yuanli , Chen Miaoxia
Published: January 2021

Anxiety and depression are common mental illnesses among nurses fighting coronavirus disease 2019 (COVID‐19). However, the precise factors that affect anxiety and depression in this population require further evaluation. This study aimed to explore factors associated with anxiety and depression among nurses fighting COVID‐19 in China. We used convenience sampling to recruit 282 nurses fighting COVID‐19 in three hospitals. Participants were questioned about demographic characteristics, daily working time, daily sleep duration, sleep quality, anxiety, depression, resilience, and coping styles. Linear regression analysis indicated that resilience (β = −0.217, P < 0.001), positive coping style (β = −0.281, P < 0.001), negative coping style (β = 0.395, P < 0.001), and sleep quality (β = 0.153, P = 0.010) were predictive factors for anxiety, and the model explained 44.20% (P < 0.001) of variability. Resilience (β = −0.239, P < 0.001), positive coping style (β = −0.222, P < 0.001), negative coping style (β = 0.152, P < 0.001), and sleep quality (β = 0.104, P = 0.003) were identified as explanatory factors for depression, and the model explained 34.50% (P < 0.001) of variability. The present study suggested that resilience, coping styles, and sleep quality could account for an individual’s levels of anxiety and depression.
‘NowMy Eyes are Open’: Latina women’s experiences in long‐term support groups for intimate partner violence survivors
Authors: Page Robin L. , Montalvo‐Liendo Nora , Nava Angeles , Chilton Jenifer
Published: January 2021

One in four women has experienced intimate partner violence in their lifetimes. The effects of intimate partner violence on women’s mental health may be long‐term; possible conditions include post‐traumatic stress disorder, depression, and anxiety. Latina women may be particularly vulnerable to long‐term effects of intimate partner violence. The purpose of this study was to describe Latina women’s experiences in long‐term support groups for survivors of intimate partner violence. Forty‐nine Latina women were interviewed about their experiences in a nurse‐led long‐term support group, with participation from 2 months to 9 years. The women ranged in age from 26 to 73 years and all but two interviews were in Spanish. Five themes emerged from the qualitative data: awakening, transformation, community, empowerment, and advocate. Women described their thoughts of still feeling the ‘ugliness of the abuse’, even years after it occurred with some women enduring abuse for as long as 32 years. The need for long‐term support groups was evident as women described the value of the group for providing support and gaining an understanding that they are not alone, or their awakening to the idea that they can have a life without abuse. Long‐term support groups give voice to Latina women who are survivors of intimate partner violence. By raising their awareness and sense of community, women survivors can be transformed and empowered to improve their lives and advocate for others who face similar struggles.
Management of the curb space allocation in urban transportation system
Authors: Yu Meigui , Bayram Armagan
Published: January 2021

Curb space management and traffic flow are two important elements of the transportation system that interact with each other and affect the overall system performance. With the growth of new mobility operators and goods delivery, the demand for access to curb space is increasing rapidly. Thus, the traditional use of curb space solely for parking is challenged and it becomes important to manage curb space effectively. Our study investigates the allocation of curb space for various uses (i.e., parking, pickup/drop‐off, and loading/unloading) so that overall transportation system performance can be enhanced. We simulate the transportation system and analyze the interactions between traffic flow and curb space usage by investigating the impact on traffic congestion of the allocation of curb spaces for different uses. We build an optimization model to determine dynamic curb space allocation decisions that ensure a smooth traffic flow. Our objective is to maximize the cities' profit from curb space allocation decisions and minimization of traffic delay. We further evaluate the value of dynamic curb space allocation policies over fixed‐allocation policies and find that the dynamic policies can result in improvements in traffic delay and total distance driven.
Effect of water content on microstructure and properties of magnesium potassium phosphate cement pastes with different magnesia‐to‐phosphate ratios
Authors: Qin Jihui , Qian Jueshi , Dai Xiaobing , You Chao , Ma Hongyan , Li Zhen
Published: January 2021

Magnesium potassium phosphate cement (MKPC) is a class of chemically bonded ceramic for special engineering applications. The selection of mass ratios of MgO‐to‐KH2PO4 (M/P) and water‐to‐cement (W/C) is an important aspect for formulating MKPC paste. This paper analyzed the stoichiometry of the primary reaction of MKPC and investigated the effect of W/C (0.14–0.40) on paste microstructure and properties at different M/P (1.5–4). At high M/P, low W/C was sufficient to complete the hydration of KH2PO4 and higher W/C yielded looser microstructure, dictating that properties of high M/P pastes were monotonic functions of W/C. However, a clear W/C threshold effect was found in medium M/P pastes at both micro‐ and macro‐levels. Low W/C below stoichiometric value suppressed the formation of K‐struvite and favored the presence of an amorphous phase, leading to intense early shrinkage, low early compressive strength, and poor long‐term water resistance. The increase in W/C above stoichiometric value resulted in the segregation of excess water and thus to porous structure, with detrimental effects on dimensional stability and strength. The micro–macro analysis highlighted the importance of stoichiometric water amount in the optimal design of MKPC.
RNA methyltransferase METTL3 induces intrinsic resistance to gefitinib by combining with MET to regulate PI3K/AKT pathway in lung adenocarcinoma
Authors: Gao Fangyan , Wang Qianqian , Zhang Chang , Zhang Chen , Qu Tianyu , Zhang Jingya , Wei Jifu , Guo Renhua
Published: January 2021

Clinical research data show that gefitinib greatly improves the progression‐free survival of patients, so it is used in advanced non‐small cell lung cancer patients with EGFR mutation. However, some patients with EGFR sensitive mutations do not have good effects on initial gefitinib treatment, and this mechanism is rarely studied. METTL3, a part of N6‐adenosine‐methyltransferase, has been reported to play an important role in a variety of tumours. In this study, we found that METTL3 is up‐regulated in gefitinib‐resistant tissues compared to gefitinib‐sensitive tissues. Cell function experiments have proved that under the treatment of gefitinib, METTL3 knockdown promotes apoptosis and inhibits proliferation of lung cancer cells. Mechanistic studies have shown that METTL3 combines with MET and causes the PI3K/AKT signalling pathway to be manipulated, which affects the sensitivity of lung cancer cells to gefitinib. Therefore, our research shows that METTL3 can be used as a molecular marker to predict the efficacy of EGFR‐TKI therapy in patients, and METTL3 may be a potential therapeutic target.
The importance of public risk perception for the effective management of pluvial floods in urban areas: A case study from Germany
Authors: Netzel Leon Maximilian , Heldt Sonja , Engler Steven , Denecke Martin
Published: January 2021

Heavy precipitation events are expected to increase in frequency and intensity in many parts of Europe as a result of climate change. These events can affect regions located far from rivers that have never been affected before. As warning times are short, there are hardly any effective emergency measures to mitigate the severe damage caused by pluvial floods. Therefore, long‐term mitigation measures are necessary for sustainable urban flood management. However, people first need to realise their personal risk in order to become active and take private precautionary measures. To get a better understanding of the processes underlying public risk perception of pluvial floods, a questionnaire‐based telephone survey was conducted analysing two case studies in western Germany. Key findings reveal that risk perceptions need to be distinguished between personal and global perception. Personal risk perception was low among the participants, while their global risk perception was far higher. The determinants of global and personal risk perception on pluvial flooding were identified. The study also showed that mitigation behaviour is influenced by personal risk perception, knowledge, education, and housing conditions. These determinants should receive attention when future risk communication and flood management strategies are developed.
Functional assembly of root‐associated microbial consortia improves nutrient efficiency and yield in soybean
Authors: Wang Cunhu , Li Yanjun , Li Mingjia , Zhang Kefei , Ma Wenjing , Zheng Lei , Xu Hanyu , Cui Baofeng , Liu Ran , Yang Yongqing , Zhong Yongjia , Liao Hong
Published: January 2021

Root‐associated microbes are critical for plant growth and nutrient acquisition. However, scant information exists on optimizing communities of beneficial root‐associated microbes or the mechanisms underlying their interactions with host plants. In this report, we demonstrate that root‐associated microbes are critical influencers of host plant growth and nutrient acquisition. Three synthetic communities (SynComs) were constructed based on functional screening of 1,893 microbial strains isolated from root‐associated compartments of soybean plants. Functional assemblage of SynComs promoted significant plant growth and nutrient acquisition under both N/P nutrient deficiency and sufficiency conditions. Field trials further revealed that application of SynComs stably and significantly promoted plant growth, facilitated N and P acquisition, and subsequently increased soybean yield. Among the tested communities, SynCom1 exhibited the greatest promotion effect, with yield increases of up to 36.1% observed in two field sites. Further RNA‐seq implied that SynCom application systemically regulates N and P signaling networks at the transcriptional level, which leads to increased representation of important growth pathways, especially those related to auxin responses. Overall, this study details a promising strategy for constructing SynComs based on functional screening, which are capable of enhancing nutrient acquisition and crop yield through the activities of beneficial root‐associated microbes.
A Family-Centered Model for Sharing Genetic Risk
Authors: Daly Mary B.
Published: January 2021

The successes of the Human Genome Project and the continuing advances of DNA technology have ushered in a new era of genomic science. Investigators around the world are using genomic technologies to advance our fundamental understanding of biologic and physiologic mechanisms in humans and other species. The ability to sequence the entire human genome exponentially expands our ability to identify the contribution of genetic variation to disease risk and other phenotypic differences within the population. Information derived from this research has the potential to contribute to disease prevention, disease prediction, and personalized treatment. These scientific advances, however, raise several ethical, legal, and social challenges. Many of these challenges, including personal and societal benefits and risks, and privacy and confidentiality, are mirrored in the current professional and public debate about the perceived conflict between personal autonomy, privacy, and confidentiality, and the potential value of sharing genomic information within the family.
Satisfying and stable couple relationships: Attachment similarity across partners can partially buffer the negative effects of attachment insecurity
Authors: Conradi Henk Jan , Noordhof Arjen , Kamphuis Jan H.
Published: January 2021

Insecure attachment in couples is negatively associated with relationship functioning. Similarity of partner attachment on the other hand might attenuate such relationship outcomes. We tested the opposing insecurity and similarity hypotheses by examining associations of attachment with relationship satisfaction and instability in a representative community sample of couples (N = 1,014). We expected: (a) negative effects of insecure attachment (main effects of actor and partner avoidance and anxiety, and interaction effects consistent with fearful‐avoidance and demand‐withdraw patterns); and (b) positive effects of similarity in avoidance and anxiety. Actor‐Partner‐Interdependence Models showed clear support for the insecurity hypothesis. Main effects of avoidance and anxiety, explained 46.2% of the variance of satisfaction, and 17.9% of instability. We conclude that reducing insecurity of attachment, in particular avoidance, must be a central target in couple therapy. Interestingly, similarity of attachment can partially buffer the negative effects of attachment insecurity. Clinical implications are discussed.
Almond consumption increased UVB resistance in healthy Asian women
Authors: Li Jason N. , Henning Susanne M. , Thames Gail , Bari Omar , Tran Patrick T. , Tseng Chi‐Hong , Heber David , Kim Jenny , Li Zhaoping
Published: January 2021

Background

Almonds are a rich source of phenolic and polyphenolic compounds, which have antioxidant activity. In vitro and in vivo studies have demonstrated that topical application of almond oil and almond skin extract reduces UVB‐induced photoaging. Ultraviolet‐B (UVB) protection by oral almond consumption has not been previously studied in humans.

Objectives

To investigate whether oral almond consumption can increase resistance to UVB radiation and reduce skin aging in healthy Asian women.

Methods

Thirty‐nine female participants (18‐45 years) with Fitzpatrick skin type II‐IV were randomly assigned to consume either 1.5 oz of almonds or 1.8 oz of pretzels daily for 12 weeks. Minimal erythema dose (MED) was determined using a standardized protocol, which determined the minimal radiation needed to induce erythema on the inner arm following UVB exposure. Facial skin texture was evaluated by two dermatologists using the Clinician's Erythema Assessment scale and Allergan Roughness scale. Facial melanin index, hydration, sebum, and erythema were determined using a cutometer.

Results

The MED was increased in the subjects consuming almonds compared to the control group consuming pretzels. There were no differences noted between the groups consuming almonds versus pretzels in Allergan roughness, melanin, hydration, or sebum on facial skin.

Conclusions

Our findings suggest that daily oral almond consumption may lead to enhanced protection from UV photodamage by increasing the MED.