bluuebunny/crossref_metadata_2025 huggingface dataset:
High‐dose corticosteroid use and risk of hospitalization for infection in patients treated with immune checkpoint inhibitors––A nationwide register‐based cohort study
Authors: Sørup Signe , Darvalics Bianka , Russo Leo , Oksen Dina , Lamy Francois‐Xavier , Verpillat Patrice , AA Khalil , HT Sørensen , Cronin‐Fenton Deirdre
Published: June 2021

High‐dose corticosteroids have been associated with increased risk of serious infection in patients with metastatic melanoma treated with immune checkpoint inhibitors targeting cytotoxic T‐lymphocyte antigen 4. This potential association needs to be examined further among patients with other cancer types and for other immune checkpoint inhibitors. We examined whether receipt of high‐dose corticosteroids was associated with increased rates of hospitalization for infection among 981 Danish renal, urothelial, and lung cancer patients followed from first administration of programmed death receptor 1 (PD‐1)/programmed death ligand 1 (PD‐L1) immune checkpoint inhibitors. Our cohort analysis was based on the information from national medical registries. During follow‐up, 522 patients (53.2%) initiated treatment with high‐dose corticosteroids and 317 patients (32.3%) experienced at least one hospitalization for infection. In analyses adjusted for age, sex, and previous use of chemotherapy/targeted therapy, initiation of high‐dose systemic corticosteroids was associated with increased rate of hospitalization for infections (hazard ratio (HR) = 2.96, 95% confidence interval (CI) = 2.41–3.65) even in patients not receiving any chemotherapy/targeted therapy (HR = 3.66, 95% CI = 2.25–5.96). Our findings showed that high‐dose corticosteroid initiation is associated with hospitalization for infection in patients treated with PD‐1/PD‐L1 immune checkpoint inhibitors. Clinicians and patients should be aware of this risk of infection when initiating treatment with high‐dose corticosteroids.
Clinicopathological analysis of primary refractory diffuse large B‐cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone chemoimmunotherapy
Authors: Suzuki Tomotaka , Maruyama Dai , Miyagi‐Maeshima Akiko , Nomoto Junko , Tajima Kinuko , Ito Yuta , Hatta Shunsuke , Yuda Sayako , Makita Shinichi , Fukuhara Suguru , Munakata Wataru , Suzuki Tatsuya , Taniguchi Hirokazu , Izutsu Koji , Kobayashi Yukio , Tobinai Kensei
Published: June 2021

Background

Approximately 15% of patients with diffuse large B‐cell lymphoma (DLBCL) experience refractory or early relapsed disease after initial rituximab‐containing chemoimmunotherapy is regarded as a primary refractory disease. Although the standard treatment for relapsed DLBCL is high‐dose chemotherapy and autologous stem cell transplantation (HDC‐ASCT), the efficacy of this approach for primary refractory DLBCL is not well understood. We aimed to investigate the clinicopathological characteristics and outcomes of patients with primary refractory DLBCL.

Methods

Sixty‐nine consecutive patients with primary refractory DLBCL who were treated at our institution were categorized as partial responders (partial response to rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone [R‐CHOP] or relapse within 6 months of R‐CHOP) (n = 41) or primary progressors (no response to R‐CHOP) (n = 28). Survival curves were constructed using the Kaplan–Meier method and compared using the log‐rank test.

Results

At initial diagnosis, 70% of patients had Ann Arbor stage III/IV disease, 56% had non‐germinal center B‐cell‐like type DLBCL, and 42% had double‐expressor lymphoma (MYC and BCL2 expression). The 3‐year overall survival rate was significantly poorer in the primary progressors group than in the partial responders’ group (15% vs. 48%, p < 0.001). Four of 17 patients treated with HDC‐ASCT were primary progressors; only one patient survived without relapse. Although double‐expressor lymphoma status did not significantly impact overall survival among all patients (p = 0.794), it was identified as an independent poor prognostic factor in HDC‐ASCT‐treated patients (p = 0.002).

Conclusions

We identified a subgroup of patients with primary refractory DLBCL who may not benefit from current treatment strategies. Further treatment development is needed to improve the outcomes of these patients.
Abusive Head Trauma through Shaking: Examination of the Perpetrators According to Dating of the Traumatic Event
Authors: Laurent‐Vannier Anne , Bernard Jonathan Y. , Chevignard Mathilde
Published: June 2021

Effective prevention of abusive head trauma (AHT) requires the identification of potential perpetrators. Current evidence suggests that infant shaking, as a mechanism of AHT, produces immediate symptoms, allowing for the dating of the event based on clinical symptoms. Determining precisely when symptoms occurred may help law enforcement to identify the perpetrator. We retrieved written legal statements and medical records from birth to age at diagnosis of 100 infants consecutively diagnosed with AHT through shaking (2011–17), using forensic expertise files. Timing of abuse allowed for the identification of perpetrators in 91 cases. All abusive events occurred inside a home (parent's or nanny's), never outdoors or in a public place, and always in the presence of only one adult. Approximately one‐third (n = 32) of the perpetrators were males (31 fathers) and two‐thirds (n = 59) were females: 49 of them were the infant's nanny and ten were the infant's mother. Infants were not described as crying habitually. Better knowledge of the context of AHT events and risk situations, including recent implementation of a new or unusual modality of childcare, and being the only adult in a home with an infant, should facilitate prevention, including targeted training and avoidance of situations associated with risk.

Key Practitioner Messages

Abusive events occur in the presence of a single adult, within the privacy of a home.

First signs of abuse most commonly occur in a recent, therefore unusual, form of childcare.

With rare exceptions, the perpetrator is either the nanny or one of the parents.

Identification of the perpetrator and better knowledge of the context of abuse should allow improving targeted prevention.
Advances in Strategies and Tools Available for Interrogation of Protein O‐GlcNAcylation
Authors: Kim Eun Ju
Published: June 2021

The attachment of a single O‐linked β‐N‐acetylglucosamine (O‐GlcNAc) to serine and threonine residues of numerous proteins in the nucleus, cytoplasm, and mitochondria is a reversible post‐translational modification (PTM) and plays an important role as a regulator of various cellular processes in both healthy and disease states. Advances in strategies and tools that allow for the detection of dynamic O‐GlcNAcylation on cellular proteins have helped to enhance our initial and ongoing understanding of its dynamic effects on cellular stimuli and given insights into its link to the pathogenesis of several chronic diseases. Furthermore, chemical genetic strategies and related tools have been successfully applied to a myriad of biological systems with a new level of spatiotemporal and molecular precision. These strategies have started to be used in studying and controlling O‐GlcNAcylation both in vivo and in vitro. In this minireview, overviews of recent advances in molecular tools being applied to the detection and identification of O‐GlcNAcylation on cellular proteins as well as on individual proteins are provided. In addition, chemical genetic strategies that have already been applied or are potentially usable in O‐GlcNAc functional are also discussed.
Transcarotid transcatheter aortic valve replacement: The best alternative?
Authors: Reilly John P. , Parikh Puja B.
Published: June 2021

Key Points

Approximately 30% of patients referred for transcatheter aortic valve replacement (TAVR) have complex aortic and/or iliofemoral anatomy.

In patients with complex vascular anatomy undergoing TAVR, patients undergoing transcarotid (TC) TAVR had lower rates of major vascular complications and no difference in all‐cause death, stroke, major bleeding, access failure, and hospital length of stay compared with transfemoral (TF) TAVR despite worse baseline risk profile.

Further adequately powered randomized studies examining the optimal access site in all‐comers undergoing TAVR and the optimal alternative access site in TAVR patients with complex PAD are warranted in this era of contemporary devices to optimize patient outcomes further.
Time for pulmonary embolism alert
Authors: Ansel Gary M.
Published: June 2021

Key Points

Pulmonary embolism response teams (PERT) are integrated institutional efforts growing worldwide.

PERT appear to optimize patient evaluation and care for pulmonary embolization.

PERT appears to be in need of improved uptake and utilization.
Acute myocardial infarction related cardiogenic shock: How important is vascular access site?
Authors: Grines Cindy L. , Leach Christopher
Published: June 2021

Key Points

Radial access is rarely used during interventions for AMI related cardiogenic shock

In this observational study, radial access was used in half of CS patients and had similar time to treatment, contrast, fluoroscopy dose and PCI success compared to femoral access.

Patients who received radial access were less sick, and the reduction bleeding complications will need to be risk adjusted.
Access routes in transcatheter aortic valve replacement: All roads lead to Rome but only one is paved
Authors: Nicolas Johny , Mehran Roxana
Published: June 2021

Key Points

The transfemoral approach is used in most patients undergoing transcatheter aortic valve replacement (TAVR) and is associated with low mortality rates as compared with alternative access sites.

The technical aspects of the procedure rather than the patient's risk profile explain most of the differences in mortality rates observed across different access routes.

Future TAVR studies are needed to establish the optimal access site when the ilio‐femoral artery anatomy is unfavorable.
Integrative computational design and construction: Rethinking architecture digitally
Authors: Knippers Jan , Kropp Cordula , Menges Achim , Sawodny Oliver , Weiskopf Daniel
Published: June 2021

Increasing the construction capacity, while at the same time significantly reducing harmful emissions and consumption of nonrenewable resources, and still providing a liveable and affordable built environment, provides a great challenge for future construction. In order to achieve this, both the productivity of construction processes and the energy and resource efficiency of construction systems have to be improved in a reciprocal process. Digital technologies make it possible to address these challenges in novel ways. The vision of this Cluster of Excellence IntCDC at the University of Stuttgart and the Max Planck Institute for Intelligent Systems is to harness the full potential of digital technologies to rethink design and construction based on integration and interdisciplinarity, with the goal of laying the methodological foundations to profoundly modernize the design and construction process and related building systems by adopting a systematic, holistic and integrative computational approach. One key objective is to develop an overarching methodology of “co‐designing” methods, processes and systems based on interdisciplinary research encompassing architecture, structural engineering, building physics, engineering geodesy, manufacturing and systems engineering, computer science and robotics, and humanities and social sciences. In this way, the Cluster aims to address the ecological, economic and social challenges and to provide the prerequisites for a high‐quality and sustainable built environment and a digital building culture.
Synthesis and Absorption Properties of Long Acenoacenes
Authors: Jančařík Andrej , Mildner Daniel , Nagata Yuuya , Banasiewicz Marzena , Olas Joanna , Kozankiewicz Boleslaw , Holec Jan , Gourdon André
Published: June 2021

Acenes, polyaromatic hydrocarbons composed of linearly fused benzene rings have received immense attention due to their performance as semiconductors in organic optoelectronic applications. Their appealing physicochemical properties, such as extended delocalization, high charge carrier mobilities, narrow HOMO‐LOMO gaps and partially radical character in the ground state make them very attractive targets for many potential applications. However, the intrinsic synthetic challenges of unsubstituted members such as high reactivity and poor solubility are still limiting factors for their wider exploitation. Herein, we report a simple general synthesis of a new family of angularly fused acenoacenes with improved stability compared to their isoelectronic linear counterparts. The synthesis and comprehensive characterization of pentacenopentacene, pentacenohexacene and hexacenohexacene, with lengths between decacene and dodecacene, are disclosed.
Impact of regionalizing ST‐elevation myocardial infarction care on sex differences in reperfusion times and clinical outcomes
Authors: Rayner‐Hartley Erin , Wong Graham C. , Fayowski Cassandra , Cairns John A. , Singer Joel , Lee Terry , Sedlak Tara , Humphries Karin H. , Perry‐Arnesen Michele , Mackay Martha , Fordyce Christopher B.
Published: June 2021

Background

Women with ST‐elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention historically experience worse in‐hospital outcomes compared to men.

Hypothesis

Implementation of a regional STEMI system will reduce care gaps in reperfusion times and in‐hospital outcomes between women and men.

Methods

1928 patients (413 women, 21.4%) presented with an acute STEMI between June 2007 and March 2016. The population was divided into an early cohort (n = 728 patients, 2007‐May 2011), and a late cohort (n = 1200 patients, June 2011–2016). The primary endpoints evaluated were reperfusion times and in‐hospital outcomes.

Results

Compared to men, women experienced significant delays in first medical contact (FMC) to arrival at the emergency room (26.0 vs. 22.0 min, p < 0.001) and FMC‐to‐device (109 vs. 101 min p = 0.001). Women had higher incidences of post‐PCI heart failure and death compared to men (p < 0.05). Following multivariable adjustment, no mortality difference was observed for women versus men (adjusted OR; 0.82; 95% confidence interval [CI], 0.51–1.34; p = 0.433) or for early versus late cohorts (adjusted OR; 1.04; 95% CI, 0.68–1.60; p = 0.856).

Conclusion

Following STEMI regionalization, women continued to experience significantly longer reperfusion times, although there was no difference in adjusted mortality. These results highlight the ongoing disparity of STEMI care between women and men, and suggest that regionalization alone is insufficient to close sex‐based care gaps.
Magnetic Carbon Nanotubes‐Silica Binary Composite for Effective Pb(II) Sequestration from Industrial Effluents: Multivariate Process Optimization
Authors: Islam Aminul , Chauhan Anjali , Javed Hina , Rais Saman , Ahmad Izhar
Published: June 2021

In this work, magnetic multiwalled carbon nanotubes‐silica binary composite (mCNT@APS) is synthesized via amide bond and utilized for the Pb(II) adsorption from aqueous solutions in batch mode. The composite is characterized using Fourier transform infrared spectroscopy (FT‐IR), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), energy‐dispersive X‐ray spectroscopy (EDS), transmission electron microscopy (TEM), X‐ray diffraction (XRD), and point of zero charge (pHpzc) studies. Three levels and three factorial Box–Behnken design in response surface methodology is employed to assess and optimize the effects of influential parameters: pH, initial concentration, and contact time. Using the desirability function, the obtained optimum conditions are pH 5.4, feed concentration 757 µg mL−1 and contact time 4 min. The electrostatic attraction between the active binding sites of adsorbent and Pb(II) at pHpzc < pH results in higher saturation capacity (79.69 mg g−1) in accordance with the best fitted non‐linearized Langmuir isotherm model. The pseudo‐second‐order model fits well to the kinetic data implying chemisorption of Pb(II) onto mCNT@APS. The material can be regenerated up to 15 sorption–desorption cycles using 5 mL of 1.5 M HNO3. The adsorbent exhibits excellent Pb(II) removal efficiency (>98%) from industrial effluents and tap water samples.
Human papillomavirus, Epstein–Barr virus, and Candida albicans co‐infection in oral leukoplakia with different degrees of dysplasia
Authors: Erira Alveiro T , Navarro Andrea Fernanda Romo , Robayo Dabeiba Adriana García
Published: June 2021

Objectives

To identify human papillomavirus (HPV), Epstein–Barr virus (EBV), and Candida albicans in oral leukoplakia with different degrees of dysplasia.

Materials and methods

An observational, cross‐sectional, descriptive study was performed using 30 formalin‐fixed and paraffin‐embedded tissues from patients with clinical suspicion of leukoplakia and confirmed diagnosis of oral dysplasia. Histological analyses were performed by two pathologists (interobserver) and dysplasias were classified as mild, moderate, or severe. Conventional PCR was used to detect HPV and EBV viruses and C. albicans. To determine the association between each microorganism with different degrees of dysplasia a Chi‐square test was employed.

Results

The tongue was the most common site for leukoplakias (71.4%) in females with a mean age of 50 years (ranging between 30 to 50 years old; 57.1%). EBV was the most frequently detected (73.3%), followed by HPV (43.3%), mainly of type 16 (40%), and C. albicans (23.3%). Significant differences were observed between degrees of dysplasia and HPV presence (p = 0.005). In lesions positive for HPV, EBV, and C. albicans the most frequent histological changes were hyperkeratosis, irregular interpapillary ridges, and loss of basal stratum cell polarity.

Conclusion

Co‐infection with human papillomavirus, Epstein Barr virus, and Candida albicans in oral leukoplakia could be associated with dysplastic changes.
FeVO4 Nanopolyhedron Photoelectrodes for Stable and Efficient Water Splitting
Authors: Chang Sheng , Wang Mingqi , Wang Chong‐Chen , Fu Xijun , Bi Hao , Zeng Qingyi
Published: June 2021

Crystalline FeVO4 nanopolyhedron (FVO NPH) photoelectrodes are successfully prepared by using an in situ solid‐state transformation from hydrothermal FeOOH films via adding vanadium precursor and following thermal treatments. The FVO NPH photoelectrodes possess uniformly dispersed polyhedral nanocrystals that directly grow on the conductive substrate with tunable film thicknesses. The unique morphology enables an outstanding photo‐electrocatalytic performance, and the optimized FVO NPH photoelectrode, which was annealed at 550 °C for 4 h with a film thickness of ∼560 nm, exhibits excellent photocurrent densities of ∼0.47 and ∼0.68 mA cm−2 at 1.0 and 1.2 V vs. Ag/AgCl, respectively. After decorating CoPi co‐catalyst, FVO/CoPi shows a highly efficient water splitting performance with O2 and H2 evolution rates of 7.53 and 15.32 μmol cm−2 h−1, respectively, which are ∼1.88 and ∼1.80 times, respectively, of these of the FVO NPH. The proposed photoelectrodes also show excellently chemical and physical stabilities in solar water splitting. This is the first time reported the preparation of well‐organized nanostructured FeVO4 films, which warrants further optimization studies on morphologies and compositions of FeVO4‐based photoelectrodes.
Catalytic Reforming of the Aqueous Phase Derived from Diluted Hydrogen Peroxide Oxidation of Waste Polyethylene for Hydrogen Production
Authors: Su Hongcai , Li Tian , Zhu Lingjun , Wang Shurong
Published: June 2021

The thermal degradation and conversion of waste polyethylene (PE) using a two‐step process including hydrothermal oxidation (HO) and aqueous phase reforming (APR) were investigated. The objective of this study was to achieve efficient disposal of waste PE and generate H2 in a mild and green way. The effects of various HO conditions on both HO and APR processes were studied. A high H2O2 concentration caused overoxidation of PE resulting in more CO2. Decreasing the H2O2 concentration weakened the overoxidation. The process using diluted H2O2 exhibited the highest selectivity for acetic acid among the produced carboxylic acids. When the HO temperature exceeded 200 °C, there was an increase in the CO2 yield during the HO process and a decrease in the H2 yield during the APR process. In addition, the effects of various monometallic and bimetallic catalysts on the reforming of the aqueous phase from the HO of PE were discussed. The highest H2 mole fraction (51.52 %) in gaseous products from the APR process was obtained with Ru/mesoporous carbon. Nevertheless, Ru−Ni exhibited a higher stability than the monometallic Ru catalyst.
Nuclear hypochromasia: Shedding light on the “lightness” of high‐grade urothelial carcinoma
Authors: Stern Evan S. , Siddiqui Momin T.
Published: June 2021

Background

The Paris system (TPS) has provided a standardized classification for reporting urinary cytology, specifically high‐grade urothelial carcinoma (HGUC). While hyperchromasia is well described in HGUC, there exists little data on nuclear hypochromasia in HGUC. Our focus was to investigate the incidence of hypochromasia in HGUC and if it should become a criterion for HGUC.

Design

All cases of HGUC at our institution for a 3‐year interval (2017–2019) using TPS were reviewed. Each case had a single ThinPrep slide and concurrent biopsy or resection specimen to confirm the diagnosis within 30 days. The presence of hypochromasia was evaluated, and cases with hypochromasia were stratified based on the tumor cell percentage. Cases with hypochromasia in 5% or greater of the tumor cells were considered “positively identified” for hypochromasia.

Results

We reviewed 117 cases of HGUC and identified nuclear hypochromasia in 12 cases (10.2%) within 5% or greater of the tumor cells. These 12 cases were further assessed based on if tumor cells showed hypochromasia in 5%–49% of the sample, or greater than 50% of the sample. Hypochromasia in 5%–49% of tumor cells was present in 8/117 cases (6.8%); whereas in 50% or greater samples 4/117 cases (3.4%) showed hypochromasia. No cases were identified where hypochromasia was noted in less than 5% of the tumor cells.

Conclusion

TPS and use of hyperchromasia as a feature of HGUC is affirmed. However, hypochromasia, while not diagnostic in isolation, is present in a sub‐set of patients with HGUC (10.2%) and should be considered as a variance noted in the nuclei of HGUC.
Socioeconomic factors, stress, hair cortisol, and white matter microstructure in children
Authors: Simon Katrina R. , Merz Emily C. , He Xiaofu , Desai Pooja M. , Meyer Jerrold S. , Noble Kimberly G.
Published: June 2021

Socioeconomic disadvantage has been linked to increased stress exposure in children and adults. Exposure to stress in childhood has been associated with deleterious effects on cognitive development and well‐being throughout the lifespan. Further, exposure to stress has been associated with differences in brain development in children, both in cortical and subcortical gray matter. However, less is known about the associations among socioeconomic disadvantage, stress, and children's white matter development. In this study, we investigated whether socioeconomic disparities would be associated with differences in white matter microstructure in the cingulum bundle, as has been previously reported. We additionally investigated whether any such differences could be explained by differences in stress exposure and/or physiological stress levels. White matter tracts were measured via diffusion tensor imaging in 58 children aged 5–9 years. Results indicated that greater exposure to stressful life events was associated with higher child hair cortisol concentrations. Further, physiological stress, as indexed by hair cortisol concentrations, were associated with higher fractional anisotropy in the cingulum bundle. These results have implications for better understanding how perceived and physiological stress may alter neural development during childhood.
Encourage, retain students with peer mentoring programs
Authors: Hope Joan
Published: June 2021

Good information delivered when students need it is critical to retaining and graduating them. That's especially true if they have the added challenges that come with having a disability.
Meet the needs of graduate students with disabilities by creating community
Authors: Hope Joan
Published: June 2021

Graduate students live very different lives than traditional undergraduate students, and disability services need to be tailored to meet those needs, said Andrea Anda Mozqueda, Ph.D., Director of Student and Campus Life and Disability Services Coordinator at the Keck Graduate Institute.
Marine mammal biodiversity and rare narwhal (Monodon monoceros) observations near northern Ellesmere Island, Canada
Authors: Carlyle Cody G. , Florko Katie R. N. , Young Brent G. , Yurkowski David J. , Michel Christine , Ferguson Steven H.
Published: June 2021

A climate‐driven decline of sea ice has increased international interest in understanding the ecology of seldom studied high‐Arctic regions projected to retain the last remnants of summer sea ice. Arctic marine mammals are vulnerable to future environmental change due to their high dependence on sea ice. We completed aerial surveys in August 2019 to document the occurrence and location of marine mammals within the recently designated Tuvaijuittuq Marine Protected Area which acts as a last refuge for ice‐associated species. We present photographic evidence of narwhals (Monodon monoceros), Atlantic walruses (Odobenus rosmarus), bearded seals (Erignathus barbatus), and ringed seals (Pusa hispida) in Archer Fjord, northern Ellesmere Island, Nunavut, Canada (81°14′–81°49′ N). We discuss these observations in the context of historical records and more recent opportunistic sightings from the region to support the hypothesis of an expansion north of the currently accepted range of narwhal. The diversity and number of observations of marine mammals in Archer Fjord is a striking contrast to the relative scarcity of the rest of the surveyed region, with very few observations of ringed seals throughout the more northerly study area. Our observations highlight opportunities to further explore high‐latitude areas that may host unique marine mammal biodiversity in the region, including narwhal.
Doping Electron Transporting Layer: An Effective Method to Enhance JSC of All‐Inorganic Perovskite Solar Cells
Authors: Liang Chao , Xing Guichuan
Published: June 2021

All‐inorganic metal‐halide CsPbBr3 perovskite has emerged as an attractive photovoltaic material for its outstanding environmental stability. However, due to the wide bandgap, the performance of CsPbBr3 perovskite solar cells (PSCs) is limited, especially for the short‐circuit current density (JSC). In this issue of Energy & Environmental Materials, Guo et al. employed Nb‐doped SnO2 as electron transporting layers (ETLs), which could greatly improve the JSC of the PSCs based on all‐inorganic CsPbBr3.
The validity of skin conductance for assessing acute pain in mechanically ventilated infants: A cross‐sectional observational study
Authors: Hu Jiale , Harrold JoAnn , Squires Janet E. , Modanloo Shokoufeh , Harrison Denise
Published: June 2021

Background

Assessing pain in mechanically ventilated infants is challenging. The assessment of skin conductance (SC) is based on the sympathetic nervous system response to stress. This study purpose was to evaluate the validity of SC for assessing pain in mechanically ventilated infants.

Methods

A prospective cross‐sectional observational design was used to study SC and its relation to: the category of procedure (i.e., painful or non‐painful); the phase of procedure (i.e., before, during and after), and referent pain measurements (i.e., Premature Infant Pain Profile‐Revised (PIPP‐R) and Neonatal Facial Coding System (NFCS)). Eligible infants were those up to 12 months of age, in intensive care units, who were mechanically ventilated, and required painful and non‐painful procedures.

Results

From October 2017 to November 2018, 130 eligible infants were identified, and 55 infants were studied. SC (number of waves per second) during painful procedures (median 0.27, interquartile range 0.2–0.4) was statistically significantly higher than those during non‐painful procedures (0, 0–0.09). SC during painful procedures was statistically significantly higher than those before (0, 0–0.07) and after painful procedures (0, 0–0.07). SC showed moderate statistically significant positive correlations with PIPP‐R (Spearman's rho = 0.4–0.62) and the four‐item NFCS (Spearman's rho = 0.31–0.67) before, during and after painful or non‐painful procedures respectively. SC had excellent performance (area under the receiver operator curve = 0.979) with excellent sensitivity (92.31%), specificity (95.42%) and negative predictive value (99.21%) but only sufficient positive predictive value (66.67%) when used to discriminate moderate‐to‐severe pain.

Conclusions

SC showed good validity for assessing pain in critically ill infants requiring mechanical ventilation.

Significance of the study

Pain assessment in mechanically ventilated infants is challenging. In this study, the validity of skin conductance (SC) for pain assessment is evaluated in the same population of infants during painful and nonpainful procedures. SC showed good validity for assessing acute pain in relation to category of procedure, phase of procedure, and referent pain measurements. SC is a promising method, especially with other pain assessment methods and other determinants of pain, in a multimodal pain assessment approach to understand the complexity of pain in mechanically ventilated infants.
Brief mindfulness training can mitigate the influence of prior expectations on pain perception
Authors: Vencatachellum Shervin , van der Meulen Marian , Van Ryckeghem Dimitri M. L. , Van Damme Stefaan , Vögele Claus
Published: June 2021

Background

Recent neuroimaging evidence suggests that mindfulness practice may mitigate the biasing influence of prior cognitive and emotional expectations on pain perception. The current study tested this hypothesis using a pain‐cueing paradigm, which has reliably been shown to elicit conditioned hypoalgesic and hyperalgesic effects. Specifically, we aimed to investigate whether the instructed use of a mindfulness compared to a suppression strategy differentially modulates the magnitudes of conditioned hypoalgesia and hyperalgesia.

Methods

Sixty‐two healthy non‐meditators were assigned to listen to either brief mindfulness or suppression instructions, in between the conditioning and testing phases of a pain‐cueing task. Participants provided ratings of anticipatory anxiety, pain intensity and pain unpleasantness throughout the task. They also completed trait and state self‐report measures of mindfulness and pain catastrophizing.

Results

Results indicated that the paradigm was successful in inducing conditioned hyperalgesic and hypoalgesic effects. Importantly, while we found evidence of cue‐induced hyperalgesia in both groups, only the suppression group reported cue‐induced hypoalgesia. No group differences in pain ratings were found for unconditioned (novel‐cued) stimuli.

Conclusions

These findings provide partial support for recently proposed predictive processing models, which posit that mindfulness may lead to a prioritization of current sensory information over previous expectations. We explore potential explanations for the asymmetrical group differences in conditioned hypoalgesia versus conditioned hyperalgesia, and discuss our results in light of recent neuroimaging insights into the neuropsychological mechanisms of mindfulness and expectancy‐driven pain modulation.

Significance

The current study provides novel insights into the working mechanisms of mindfulness‐driven pain modulation. Our data suggest that brief mindfulness training may reduce the influence of prior beliefs and expectations on pain perception. This finding adds to growing evidence suggesting that mindfulness may alleviate pain via neuropsychological mechanisms opposite to those typically observed in conditioning/placebo procedures and other cognitive manipulations. These unique mechanisms underline the potential of mindfulness as an alternative to traditional cognitive pain regulatory strategies.
Characterizing white matter alterations subject to clinical laterality in drug‐naïve de novo Parkinson's disease
Authors: Xiao Yiming , Peters Terry M. , Khan Ali R.
Published: June 2021

Parkinson's disease (PD) is a progressive neurodegenerative disorder that is characterized by a range of motor and nonmotor symptoms, often with the motor dysfunction initiated unilaterally. Knowledge regarding disease‐related alterations in white matter pathways can effectively help improve the understanding of the disease and propose targeted treatment strategies. Microstructural imaging techniques, including diffusion tensor imaging (DTI), allows inspection of white matter integrity to study the pathogenesis of various neurological conditions. Previous voxel‐based analyses with DTI measures, such as fractional anisotropy and mean diffusivity have uncovered changes in brain regions that are associated with PD, but the conclusions were inconsistent, partially due to small patient cohorts and the lack of consideration for clinical laterality onset, particularly in early PD. Fixel‐based analysis (FBA) is a recent framework that offers tract‐specific insights regarding white matter health, but very few FBA studies on PD exist. We present a study that reveals strengthened and weakened white matter integrity that is subject to symptom laterality in a large drug‐naïve de novo PD cohort using complementary DTI and FBA measures. The findings suggest that the disease gives rise to tissue degeneration and potential re‐organization in the early stage.
Cutaneous T‐cell lymphomas—An update 2021
Authors: Kempf Werner , Mitteldorf Christina
Published: June 2021

Cutaneous T‐cell lymphomas (CTCL) represent the majority of primary cutaneous lymphomas (CL). Mycosis fungoides (MF) and cutaneous CD30+ lymphoproliferative disorders account for 80% of all CTCL. CTCL show overlapping histological features. Thus clinical‐pathological correlation is of importance to achieve final diagnosis. MF shows a characteristic evolution with patches, plaques, and in a subset of patients (10%–20%) with tumors. Therapy is stage‐adapted with skin‐directed therapies such as UV‐light therapies and corticosteroids in early disease stage (i.e., patch and limited plaque stage) and systemic therapies (retinoids, interferon, mono chemotherapy, targeted therapy) and/or radiation therapy (local or total skin beam electron) in advanced stages. Novel therapies include targeted therapy such as mogamulizumab (anti‐CCR4) or brentuximab vedotin (anti‐CD30) and histone deacetylase inhibitors. Considering the impact of targeted therapies, biomarkers such as CD30 are not only crucial for the diagnosis and correct classification of an individual lymphoma case, but also for therapy as they may represent therapeutic targets. In the recently revised WHO classification 2017 and the updated WHO‐EORTC classification for CL 2018, primary cutaneous CD8+ acral T‐cell lymphoma has been introduced as a new still provisional entity. It displays characteristic clinical, histological, and phenotypic features and exhibits an excellent prognosis. Rare, but aggressive CTCL include cutaneous primary cutaneous aggressive epidermotropic CD8‐positive T‐cell lymphoma and cutaneous gamma/delta T‐cell lymphoma, which present with rapid onset of necrotic or ulcerated plaques and tumors. As they have a poor prognosis, treatment includes multiagent chemotherapy and hematopoietic stem cell transplantation.
Personalized medicine for Hodgkin lymphoma: Mitigating toxicity while preserving cure
Authors: Longley Jemma , Johnson Peter W. M.
Published: June 2021

The treatment of classical Hodgkin lymphoma in young patients is one of the success stories of modern medicine. The use of risk‐ and response‐adapted approaches to guide treatment decisions has led to impressive cure rates while reducing the long‐term toxicity associated with more intensive therapies. Tissue biomarkers have not yet proven more effective than clinical characteristics for risk stratification of patients at presentation, but functional imaging features such as metabolic tumor volume may be used to predict response, if early observations can be validated. The success of treatment in younger patients has unfortunately not been mirrored in those over 60, where complex decision‐making is often required, with a paucity of data from clinical trials. The use of PD1 blocking antibodies and brentuximab vedotin in this cohort, either alone or in combination with chemotherapy, may provide attractive options. The incorporation of frailty assessment, quality‐of‐life outcomes, and specialist geriatric input is also important to ensure the best outcomes for this diverse group.
Feasible kidney donation with living marginal donors, including diabetes mellitus
Authors: Yoshinaga Kasumi , Araki Motoo , Wada Koichiro , Sekito Takanori , Watari Shogo , Maruyama Yuki , Mitsui Yosuke , Sadahira Takuya , Kubota Risa , Nishimura Shingo , Edamura Kohei , Kobayashi Yasuyuki , Tanabe Katsuyuki , Takeuchi Hidemi , Kitagawa Masashi , Kitamura Shinji , Wada Jun , Watanabe Masami , Watanabe Toyohiko , Nasu Yasutomo
Published: June 2021

Objectives

To compare the donor outcomes of living donor kidney transplantation between standard donors (SDs) and marginal donors (MDs) including diabetic patients (MD + DM).

Methods

MDs were defined according to Japanese guideline criteria: (a) age >70‐years, (b) blood pressure ≤130/80 mmHg on hypertension medicine, (c) body mass index >25 to ≤32 kg/m2, (d) 24‐h creatinine clearance ≥70 to <80 ml/min/1.73 m2, and (e) hemoglobin A1c > 6.2 or ≤6.5 with oral diabetic medicine. Fifty‐three of 114 donors were MDs. We compared donor kidney functions until 60 months postoperatively.

Results

No kidney function parameters were different between SDs and MDs. When comparing SD and MD + DM, MD + DM had a lower postoperative eGFR (48 vs. 41 (1 (month), p = .02), 49 vs. 40 (12, p < .01), 48 vs. 42 (24, p = .04), 47 vs. 38 (36, p = .01)) and the percentage of residual eGFR (SD vs. MD + DM: 63 vs. 57 (1 (month), p < .01), 63 vs. 57 (2, p < .01), 64 vs. 56 (12, p < .01), 63 vs. 57 (24, p < .01), 63 vs. 52 (36, p = .02)). However, when MD with a single risk factor of DM was compared to SD, the difference disappeared. Nine out of 12 (75%) MD + DM had ≥2 risk factors.

Conclusions

Although long‐term observation of donor kidney function is necessary, careful MD + DM selection had the potential to expand the donor pool.
Relationship of transitional regulatory B and regulatory T cells and immunosuppressive drug doses in stable renal transplant recipients
Authors: Ibrahim Eman H , Aly Mostafa , Morath Christian , Sayed Douaa M , Ekpoom Naruemol , Opelz Gerhard , Süsal Caner , Daniel Volker
Published: June 2021

Objectives

Regulatory B cells (Bregs) and T cells (Tregs) are thought to be involved in the regulation of graft acceptance in renal transplant recipients. However, mechanisms that affect Breg differentiation and interaction with Tregs are rather unclear.

Methods

Using eight‐color‐fluorescence flow cytometry, Tregs and CD19+ CD24hiCD38hi Bregs were analyzed in whole blood samples of 80 stable kidney transplant recipients, 20 end‐stage renal disease (ESRD) patients and 32 healthy controls (HC). In addition, differentiation of Bregs and Tregs was studied in different micromilieus using cocultures with strongly enriched B‐lymphocytes and autologous peripheral blood mononuclear cells stimulated with CpG and phytohemagglutinin.

Results

Bregs were higher in HC than in ESRD patients and lowest in transplant recipients. Bregs were higher early as compared to late posttransplant. Posttransplant, high Bregs were associated with higher glomerular filtration rate (GFR) and lower C‐reactive protein (CRP). Higher doses and blood levels of ciclosporine, tacrolimus, and mycophenolate mofetil as well as higher doses of steroids were not associated with low Bregs. In contrast, most Treg subsets were lower when blood levels of ciclosporine, tacrolimus, and mycophenolate mofetil were higher. Tregs were not associated with Bregs, GFR, CRP plasma levels, and occurrence of rejection or infection. In vitro, differentiation of Bregs was strongly dependent on T cell support and was blocked by excessive or lacking T‐cell help. Tregs were not associated with Breg numbers in vitro.

Conclusion

Bregs appear to be insensitive to high doses of posttransplant immunosuppressive drugs. The protracted Breg decrease posttransplant might be caused by impaired T cell support attributable to immunosuppressive drugs.
Two Decades of Chromatic Orthogonality
Authors: Bochet Christian G.
Published: June 2021

Chromatic orthogonality is defined as the possibility of independently addressing different photosensitive sites using light beams of different colors. After its initial study in synthetic chemistry, this property has been applied in many other fields, such as lithography, chemical biology and catalysis. This short account gives an overview of some of the significant work in the field in the last two decades.
Effects of Imbalance of Self‐ and Other‐Care on Counselors' Burnout
Authors: Ko Hyeyun , Lee Sang Min
Published: June 2021

This study was aimed at identifying counselor profiles based on their balance between self‐care and caring for others, and examining how these profiles differ by levels of burnout and life satisfaction. We conducted a latent profile analysis of 292 Korean counselors and identified four groups: (a) low care, (b) typical care, (c) high care, and (d) low self‐care/high other‐care. Of these, the typical care and high care groups had lower levels of incompetence and deterioration in personal life and higher levels of life satisfaction compared with the low self‐care/high other‐care group. Counselor self‐awareness, education level, work experience, and number of handled cases were found to be differentiators among the four profiles. Limitations and implications are discussed.
A Metastudy of Journal of Counseling & Development: An Analysis of Publication Characteristics From 2000 to 2019
Authors: Anderson Billie , Barstack Samantha , Erford Bradley T.
Published: June 2021

This metastudy evaluates trends and patterns in the author and article characteristics found in the Journal of Counseling & Development from 2000 to 2019. Special attention was given to research articles to more accurately identify and evaluate the research advancing the counseling profession. Findings suggest significant shifts in authorship (e.g., majority women authors, more international lead authors, 3.18 authors per article), content type (e.g., more research and international counseling articles and fewer practice, theory, trends, and profiles articles; slightly more counseling process articles; slightly fewer multicultural issues and health/well‐being articles), research design (i.e., more intervention articles; more true/quasi‐experimental, single‐subject research, and meta‐analytic designs and fewer correlational designs); participants (i.e., slightly larger sample sizes); and statistics used in studies (i.e., more basic or intermediate and fewer advanced statistics). Although the use of effect size and sample reliability estimates increased, the use of sample validity estimates did not.
Evaluation of Trauma, Forgiveness, and Well‐Being Among African Americans
Authors: Balkin Richard S. , Mendoza Samantha M. , Hendricks LaVelle , Harris Nephaterria A. , Flores Serena , Casillas Carolina , Wood Alyssa
Published: June 2021

Discrimination and trauma are prevalent experiences among African Americans. In this study, 173 African American adults completed measures on the prevalence of traumatic experiences, trauma symptoms, the process of forgiveness, and well‐being. Participants endorsed the occurrence of traumatic events in their lives, associated traumatic symptoms, and the intrapersonal forgiveness process. The hypothesized model of trauma forgiveness and well‐being was partially supported. The hypothesized model related to processing forgiveness was evident. However, no relationship was found between trauma symptoms and the initial phase of forgiveness. Furthermore, no relationship was found between the final phase of the forgiveness model and well‐being. For African American clients, working through issues of conflict and forgiveness may be a unique process separate and distinct from processing through issues of trauma and well‐being.
Stimulus generalization of behavioral history: Interspecies generality and persistence of generalization gradients
Authors: Okouchi Hiroto , Nakamura Satoshi , Watanabe Sota , Lattal Kennon A.
Published: June 2021

Four pigeons were exposed to a tandem variable‐interval (VI) fixed‐ratio (FR) schedule in the presence of a 50‐pixel (about 15 mm) square or an 80‐pixel (about 24 mm) square and to a tandem VI differential‐reinforcement‐of‐low‐rate (DRL) schedule when a second 80‐pixel or 50‐pixel square was present. The values of the VI and FR schedules were adjusted to equate reinforcement rates in the two tandem schedules. Following this, a square‐size continuum generalization test was administered under a fixed‐interval (FI) schedule or extinction. In the first testing session, response frequency was a graded function of the similarity of the test stimuli to the training stimuli for all pigeons. These systematic generalization gradients persisted longer under the FI schedule than under extinction.
Vasa expression is associated with sex differentiation in the Asian yellow pond turtle, Mauremys mutica
Authors: Liu Xiaoli , Zhu Yanyu , Zhao Yanyan , Wang Yakun , Li Wei , Hong Xiaoyou , Yu Lingyun , Chen Chen , Xu Hongyan , Zhu Xinping
Published: June 2021

Vasa, one of the best‐studied germ cell markers plays a critical role in germ cell development and differentiation in animals. Vasa deficiency would lead to male‐specific sterility in most vertebrates, but female sterility in the fly. However, the role of the vasa gene involved in germ cell differentiation is largely elusive. Here, we first characterized the expression profile of vasa products in the Asian yellow pond turtle by quantitative reverse‐transcription polymerase chain reaction and fluorescence immunostaining. The results showed that vasa messenger RNA (mRNA) is initially detected in embryos at stage 16, and then dramatically increased in embryos at stage 19. In particular, like the sex‐related genes, vasa mRNA exhibited differential expression in embryos between the male‐producing temperature (MPT, 25°C) and the female‐producing temperature (FPT, 33°C), whereas there was no difference in methylation levels of vasa promoter detected between FPT and MPT. In contrast, in the adult Asian yellow pond, the level of vasa mRNA was much higher in the testis than ovary. Moreover, the immunostaining on testicular sections and cells showed that Vasa protein was exclusively expressed in germ cells: Weak but detectable in spermatogonia, highest in spermatocytes, moderate and concentrated in chromatid bodies in spermatids and spermatozoa, and bare in somatic cells. The expression profile of Vasa protein is similar in turtle species studied so far but distinct from those in fish species in this study. The findings of this study would provide new insights into our understanding of the conservation and divergence of the vasa gene, even other germ cell genes across phyla.