bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal associations between time‐varying insomnia symptoms and all‐cause health care services utilization among middle‐aged and older adults in the United States
Authors: Mahmood Asos , Kedia Satish , Dobalian Aram , Chang Cyril F. , Ahn SangNam
Published: March 2022

Objective

To examine longitudinal associations between time‐varying insomnia symptoms (difficulty initiating sleep, difficulty maintaining sleep, early‐morning awakenings, and nonrestorative sleep) and all‐cause health care services utilization (HSU), including overnight hospital stays, nursing home stays, and home health care services among middle‐aged and older adults.

Data Sources

The Health and Retirement Study (HRS), a nationwide, population‐representative survey of primarily middle‐aged and older adults in the United States.

Study Design

This study is an analysis of prospective data from the HRS for a cohort of 13,168 adults (aged ≥50 years; females = 57.7%). Study participants were followed for 16 years. This study focuses on the associations between time‐varying insomnia symptoms, both cumulatively and independently, and repeated HSUs. A marginal structural modeling approach was used to capture time‐varying biological, psycho‐cognitive, and behavioral health factors, and to adjust for selection bias such as differential loss to follow‐up. Generalized estimating equations were employed to compute average marginal effects and their 95% confidence intervals.

Data Collection/Extraction Methods

We extracted longitudinal data from 2002 through 2018 waves of the HRS.

Principal Findings

Experiencing higher numbers of insomnia symptoms on a cumulative scale was associated with higher probabilities of HSU. For instance, the likelihood of overnight hospital stays for individuals reporting one symptom increased from 4.7 percentage points on average (95% CI: 3.7–5.6, p < 0.001), to 13.9 percentage points (95% CI: 10.3–17.5, p < 0.001) for those reporting four symptoms, relative to individuals experiencing no insomnia symptoms. Further, experiencing each of difficulty initiating and maintaining sleep, and nonrestorative sleep, as standalone symptoms, was associated with a higher likelihood of HSU when compared to those not experiencing the symptoms.

Conclusions

The results demonstrate the potential consequences and adverse impacts of insomnia symptoms on HSU among middle‐aged and older adults. Future investigations should focus on the underlying causes and health systems pathways linking insomnia symptoms to HSU.
Genome‐wide identification and comparative analysis of lipocalin families in Lepidoptera with an emphasis on Bombyx mori
Authors: Zhou Yan‐Yan , Jin Yue , Liu Shuai‐Qi , Xu Shi‐Liang , Huang Yu‐Xin , Xu Yu‐Song , Shi Lian‐Gen , Wang Hua‐Bing
Published: March 2022

Lipocalins exhibit functional diversity, including roles in retinol transport, invertebrate cryptic coloration, and stress response. However, genome‐wide identification and characterization of lipocalin in the insect lineage have not been thoroughly explored. Here, we found that a lineage‐specific expansion of the lipocalin genes in Lepidoptera occurred in large part due to tandem duplication events and several lipocalin genes involving insect coloration were expanded more via tandem duplication in butterflies. A comparative analysis of conserved motifs showed both conservation and divergence of lepidopteran lipocalin family protein structures during evolution. We observe dynamic changes in tissue expression preference of paralogs in Bombyx mori, suggesting differential contribution of paralogs to specific organ functions during evolution. Subcellular localization experiments revealed that lipocalins localize to the cytoplasm, nuclear membrane, or nucleus in BmN cells. Moreover, several lipocalin genes exhibited divergent responses to abiotic and biotic stresses, and 1 lipocalin gene was upregulated by 300 fold in B. mori. These results suggest that lipocalins act as signaling components in defense responses by mediating crosstalk between abiotic and biotic stress responses. This study deepens our understanding of the comprehensive characteristics of lipocalins in insects.
Stereotactic radiosurgery for melanoma brain metastases: Concurrent immune checkpoint inhibitor therapy associated with superior clinicoradiological response outcomes
Authors: Shanker Mihir D , Garimall Sidyarth , Gatt Nick , Foley Heath , Crowley Samuel , Le Cornu Emma , Muscat Kendall , Soon Wei , Atkinson Victoria , Xu Wen , Watkins Trevor , Huo Michael , Foote Matthew C , Pinkham Mark B
Published: March 2022

Introduction/purpose

This study assessed long‐term clinical and radiological outcomes following treatment with combination stereotactic radiosurgery (SRS) and immunotherapy (IT) for melanoma brain metastases (BM).

Methods

A retrospective review was performed in a contemporary cohort of patients with melanoma BM at a single tertiary institution receiving Gamma Knife® SRS for melanoma BM. Multivariate Cox proportional‐hazards modelling was performed with a P <0.05 for significance.

Results

101 patients (435 melanoma BM) were treated with SRS between January‐2015 and June‐2019. 68.3% of patients received IT within 4 weeks of SRS (concurrent) and 31.7% received SRS alone or non‐concurrently with IT. Overall, BM local control rate was 87.1% after SRS. Median progression free survival was 8.7 months. Median follow‐up was 29.2 months. On multivariate analysis (MVA), patients receiving concurrent SRS‐IT maintained a higher chance of achieving a complete (CR) or partial response (PR) [HR 2.6 (95% CI: 1.2–5.5, P = 0.012)] and a reduced likelihood of progression of disease (PD) [HR 0.52 (95% CI: 0.16–0.60), P = 0.048]. Any increase in BM volume on the initial MRI 3 months after SRS predicted a lower likelihood of achieving long‐term CR or PR on MVA accounting for concurrent IT, BRAF status and dexamethasone use [HR = 0.048 (95% CI: 0.007–0.345, P = 0.0026)]. Stratified volumetric change demonstrated a sequential relationship with outcomes on Kaplan–Meier analysis.

Conclusion

Concurrent SRS‐IT has favourable clinical and radiological outcomes with respect to CR, PR and a reduced likelihood of PD. Changes in BM volume on the initial MRI 3 months after SRS were predictive of long‐term outcomes for treatment response.
Conditional repeatability and the variance explained by reaction norm variation in random slope models
Authors: Schielzeth Holger , Nakagawa Shinichi
Published: March 2022

Individuals differ in average phenotypes and in sensitivity to environmental variation. Such context sensitivity can be modelled as random slope variation. Random slope variation implies that the proportion of between‐individual variation varies across the range of a covariate (environment/context/time/age) and has thus been called ‘conditional’ repeatability.

We propose to put conditional repeatabilities in perspective of the total phenotypic variance and suggest a way of standardization using the random slope coefficient of determination . Furthermore, we illustrate that the marginalized repeatability averaged across an environmental gradient offers a biologically relevant description of between‐individual variation.

We provide simple equations for calculating key descriptors of conditional repeatabilities, clarify the difference between random intercept variation and average between‐individual variation and make recommendations for comprehensive reporting.

While we introduce the concept with individual variation in mind, the framework is equally applicable to other type of between‐group/cluster variation that varies across some (environmental) gradient.
Screening tools to identify patients with unmet palliative care needs in the emergency department: A systematic review
Authors: Kirkland Scott W. , Yang Esther H. , Garrido Clua Miriam , Kruhlak Maureen , Campbell Sandra , Villa‐Roel Cristina , Rowe Brian H.
Published: March 2022

Objectives

This systematic review identified and assessed psychometric properties of the available screening tools to identify patients with unmet palliative care (PC) needs in the emergency department (ED).

Methods

A comprehensive search of electronic databases and the gray literature was conducted. Two independent reviewers completed study screening and inclusion, data extraction, and quality assessment. A descriptive summary of the results was reported using median of medians and interquartile ranges (IQRs).

Results

A total of 35 studies were included, involving the assessment of 14 unique screening tools. The most commonly used screening tool was the surprise question (SQ; n = 12 studies), followed by the Palliative Care and Rapid Emergency Screening (P‐CaRES) tool (n = 8), and the screening for palliative and end‐of‐life care needs in the emergency department (SPEED) instrument (n = 4). Twelve of the included studies reported on the psychometric properties of the screening tools, of which eight of these studies assessed the performance of the SQ to predict patient mortality. Overall, the median sensitivity (63%, IQR 38%–78%) and specificity (75%, IQR 57%–84%) of the SQ to predict mortality at 1 or 12 months was moderate. While the median positive predictive value of the SQ was low (32%, IQR 16%–40%), the median negative predictive value was high (91%, IQR 88%–95%). Across the studies, the proportion of patients identified as having unmet PC based on the criteria of the screening tools ranged from 5% to 83%.

Conclusions

This review identified 14 unique screening tools used to identify adult patients with unmet PC needs in the ED. One screening tool, the SQ, was found to have moderate sensitivity and specificity to accurately predict future patient mortality. Additional research is needed to better understand the clinical value of this and the other available tools prior to their widespread implementation.
Carbetocin vs. oxytocin at elective caesarean delivery: a double‐blind, randomised, controlled, non‐inferiority trial of low‐ and high‐dose regimens
Authors: McDonagh F. , Carvalho J.C. A. , Abdulla S. , Cordovani D. , Downey K. , Ye X.Y. , Farine D. , Morais M. , Balki M.
Published: March 2022

Carbetocin or oxytocin are given routinely as first‐line uterotonic drugs following delivery of the neonate during caesarean delivery to prevent postpartum haemorrhage. Low doses may be as effective as high doses with a potential reduction in adverse effects. In this double‐blind, randomised, controlled, non‐inferiority trial, we assigned low‐risk patients undergoing elective caesarean delivery under spinal anaesthesia to one of four groups: carbetocin 20 μg; carbetocin 100 μg; oxytocin 0.5 IU bolus + infusion; and oxytocin 5 IU bolus + infusion. The study drug was given intravenously after delivery of the neonate. Uterine tone was assessed by the obstetrician 2, 5 and 10 minutes after study drug administration according to an 11‐point verbal numerical rating scale (0 = atonic, 10 = excellent tone). The primary outcome measure was uterine tone 2 min after study drug administration. The pre‐specified non‐inferiority margin was 1.2 points on the 11‐point scale. Secondary outcomes included uterine tone after 5 and 10 minutes, use of additional uterotonics, blood loss and adverse effects. Data were available for 277 patients. Carbetocin 20 μg resulting in uterine tone of (median (IQR [range])) 8 (7–8 [1–10]) was non‐inferior to carbetocin 100 μg with tone 8 (7–9 [3–10]), median (95%CI) difference 0 (−0.44–0.44). Similarly, oxytocin 0.5 IU with tone 7 (6–8 [3–10]) was non‐inferior to oxytocin 5 IU with tone 8 (6–8 [2–10]), median (95%CI) difference 1 (0.11–1.89). Carbetocin 20 μg was also non‐inferior to oxytocin 5 IU, and oxytocin 0.5 IU was non‐inferior to carbetocin 100 μg. Uterine tone after 5 and 10 minutes, use of additional uterotonics, blood loss and adverse effects were similar in all groups.
Impact of stone volume on treatment outcomes of percutaneous nephrolithotripsy
Authors: Umemoto Tatsuya , Hasegawa Masanori , Kawakami Masayoshi , Nakano Mayura , Nitta Masahiro , Kawamura Yoshiaki , Shoji Sunao , Miyajima Akira
Published: March 2022

Purpose

We aimed to evaluate the impact of stone volume on the surgical outcomes of patients who underwent percutaneous nephrolithotripsy, which is the preferred treatment for renal and upper ureteral stones.

Materials and Methods

This retrospective study included 37 patients who underwent percutaneous lithotripsy between 2013 and 2019. Preoperative and postoperative stone volumes were quantified using computed tomography scan data.

Results

The mean preoperative and postoperative stone volumes were 10.7 cm3 (1.1–50.2 cm3) and 2.1 cm3 (0–18.2 cm3), respectively. The correlation coefficient between the stone volume and maximum stone length was 0.62 (P < .01). A residual stone volume of >5 mm was observed in 17 cases (45.9%). Thirteen cases underwent secondary treatment (35.1%) who had a preoperative stone volume of >15 cm3 or a postoperative stone volume of <2 cm3. The areas under the curve for the stone volume for treatment success and the requirement for secondary treatment were 0.701 and 0.739, respectively, and were higher than those of stone length (0.638 and 0.558) and shape (0.644 and 0.641).

Conclusions

Measurement of stone volume using three‐dimensional imaging is simple and greatly impacted the course of stone treatment. Information on stone volume may predict an increased likelihood of secondary treatment in patients with a preoperative stone volume of >15 cm3.
The brain during life and in adjudicating death: Reduced brain identity of persons as a critique of the neurological criteria of death
Authors: Lee Joseph
Published: March 2022

The determination of death by neurological criteria (brain death) is practiced in at least 80 countries, though it is a matter of continuing controversy. At the same time, the brain is central to human life, thinking, and behavior; however, a growing “neurocentrism” or a brain‐focused image of human identity became established in most Western and in many non‐Western societies and acts as a forceful ideology. This paper seeks a broader theoretical and sociocultural basis to approaching death bioethically by analyzing criticisms aimed at a neurologically focussed vision of human life, and then turning these towards the brain death criteria exposed to the criticism. The overall critique of the “neuro‐self” has scope to offer alternative perspectives to the contested issues in brain‐death criteria. Specifically, the paper examines two major shortcomings of a narrow brain view of life and culture. First, it considers the reduction of the individual to the brain: this is the crux of the neurological way of determining death, and is a way that is seemingly context‐independent and culturally neutral. Second, it considers how dimensions of society and culture for humans are detached from the brain and have little impact on clinical practice and thinking in brain‐death criteria; however, a deeper exploration reveals that they actually have direct relevance and that social and cultural factors have greater contributions to make to the current debates.
An intrapartum calculator for predicting cesarean birth due to dystocia: Preliminary findings from a single‐center study in Korea
Authors: Yang YunSeok
Published: March 2022

Background

Previous calculators based on antepartum or pre‐labor factors preclude intrapartum counseling. We aimed to develop a reliable, programmable, intrapartum calculator to predict the risk of cesarean birth (CB) due to dystocia and to increase the discriminatory accuracy of the predictive model.

Methods

Data were obtained retrospectively for 1326 singleton term deliveries with cephalic presentation. Two predictive multivariable logistic regression analysis models were constructed using pre‐active labor variables alone (model A) or with active labor variables (model B). The discriminatory accuracies and goodness‐of‐fit of the models were compared using receiver operating characteristic (ROC) curves or −2log‐likelihood ratios, Akaike information criterion (AIC), and Bayesian information criterion (BIC), respectively. Both models were internally validated using a bootstrapping procedure.

Results

Model A yielded an area under the curve (AUC) of 0.859 and adequate goodness of fit (P = 0.970). Model B yielded a significantly higher AUC of 0.887 and adequate goodness of fit (P = 0.624), as well as a significantly lower AIC and BIC (P < 0.001). Internal validation revealed a minimal optimism of 0.0070491 and 0.0068976 for models A and B, respectively. Finally, the logistic regression equations were converted into programmable calculators to yield easy‐to‐understand basic (model A) and additional intrapartum CB calculators (model B).

Conclusions

The programmable calculators developed herein can augment intrapartum counseling. Our findings suggest that the risk of CB due to dystocia during labor should be estimated using a calculator that corresponds to labor progression. Further studies should explore external validation of these statistical models before translation to a clinical setting.
A universal pharmacy: Possible self‐medication using tree balsam by multiple Atlantic Forest mammals
Authors: Kaisin Olivier , Rocha Fernanda Corrêa , Amaral Rodrigo Gonçalves , Bufalo Felipe , Sabino Gabriel Pavan , Culot Laurence
Published: March 2022

We present camera trap evidence of 10 Atlantic Forest mammals fur‐rubbing, licking, or biting balsam from cabreúvas (Myroxylon peruiferum, Fabaceae), native trees used in traditional medicine for their prophylactic and therapeutic virtues. Given the antiparasitic properties of cabreúvas, mammals may be using the balsam as topical self‐medication to repel ectoparasites.

Abstract in Portuguese is available with online material.
Unilateral ulcerations on the forehead and scalp
Authors: Tormo-Mainar Sara , Pesqué David , Olmos-Alpiste Ferran , Deza Gustavo , March-Rodriguez Alvaro , Pujol Ramon M.
Published: March 2022

We describe a patient with unilateral ulcerations on the forehead and scalp, occurring 3 months after herpes zoster infection. Further investigations were unremarkable. Histology showed epidermal and upper dermal ulceration associated with a mild nonspecific dermal inflammatory infiltrate composed of lymphoid cells and histiocytes.
Outcome measures and methods of assessment of soft‐tissue augmentation interventions in the context of dental implant therapy: A systematic review of clinical studies published in the last 10 years
Authors: Avila‐Ortiz Gustavo , Couso‐Queiruga Emilio , Pirc Miha , Chambrone Leandro , Thoma Daniel S.
Published: March 2022

Aim

The aim of the study was to identify and report outcome measures and methods of assessment on soft‐tissue augmentation interventions in the context of dental implant therapy reported in clinical studies published in the last 10 years.

Material and Methods

The protocol of this PRISMA 2020‐compliant systematic review was registered in PROSPERO (CRD42021252214). A literature search was conducted to identify articles that met the pre‐established eligibility criteria. Data of interest, with an emphasis on outcome measures, were extracted. For each outcome, specific methods and timing of assessment were described in detail. Following a critical qualitative analysis of the data, outcome measures were categorized. Primary outcomes were identified and the frequency of reporting in the selected articles was calculated. Additionally, risk of bias assessments were performed for individual articles and primary outcomes.

Results

Ninety‐two articles, of which 39 reported randomized controlled trials (RCTs), 20 reported non‐RCTs, and 33 reported case series studies, were selected. Outcome measures were categorized into either investigator‐evaluated outcome measures (i.e., clinical, digital imaging, esthetic, histologic, biomarker, and safety) or patient‐reported outcome measures (PROMs). Clinical outcomes were the most frequently reported type of outcome. Considering all categories, the most frequently reported primary outcomes were facial mucosa thickness assessed with clinical methods (22.83%), facial keratinized mucosa width assessed with clinical methods (19.57%), facial mucosal margin position/recession assessed with clinical methods (18.48%), facial mucosa thickness assessed with digital imaging methods (11.96%), facial soft‐tissue volume assessed with digital imaging methods (9.78%), and supracrestal tissue height assessed with clinical methods (9.78%). No distinguishable patterns of association between specific types or quality (level of bias) of clinical studies and the choice of primary outcomes were observed.

Conclusion

Clinical research on peri‐implant soft‐tissue augmentation has progressively increased in the last 10 years. Although clinical outcome measures were the most frequently reported outcomes in the selected literature, trends in the field are indicative of a shift from traditional clinical assessment methods to the use of digital technologies. PROMs were generally underreported but should be considered an integral methodological component in future clinical studies.
The impact of experience on recurrence rates after biopsy punch excision for pilonidal disease
Authors: Basso Luigi , Pietroletti Renato , Micarelli Alessandro , Bicaj Agreta , Costi Umberto , Crocetti Daniele , D'Ermo Giuseppe , Gallo Gaetano
Published: March 2022

Aim

We present the outcomes and the recurrences of 848 patients with pilonidal disease (PD) treated by biopsy punch excision (BPE) and we weigh our results against progressively obtained operative experience. BPE is a modified ‘merged’ version of both the Bascom ‘pit picking’ procedure and the Gips procedure. It employs biopsy punches of different calibre, depending on whether treatment is in the natal cleft (calibre as small as possible) or lateral (larger calibre punches or even small incision). Sometimes this procedure is referred to as the Bascom–Gips procedure.

Methods

In all, 848 consecutive patients with PD were treated from January 2011 until December 2016 (sex 622 [73.4%] men and 226 [26.6%] women; median age 26.2 years, mean age 24.6 ± 28.99 [range 14–55] years, men 25.1 years, women 24.8 years). Of these 848 patients, 287 were operated in 2011–2012, 301 in 2013–2014 and 260 in 2015–2016. The recurrence rates were recorded 12, 24 and 60 months after surgery both cumulatively and by examining the outcomes of the three biennia individually (years of treatment 2011–2012 or group A, 2013–2014 or group B, 2015–2016 or group C).

Results

The mean operating time was 34 ± 24.45 min. Postoperative complications included early (<24 h; n = 22 or 2.6%) and delayed (>24 h; n = 26 or 3.1%) postoperative bleeding. Postoperative fluid collections (<2 weeks) occurred in 83/848 patients (9.8%) and included haematoma (n = 25) and seroma (n = 58). Full recovery was obtained after a mean of 21 ± 12.72 days and work/school/university activities were resumed after a mean of 4 ± 12.02 days. Twelve‐, 24‐ and 60‐month follow‐ups were possible in 725 (85.5%), 682 (80.4%) and 595 (70.2%) patients out of 848. An overall significant (ꭓ2 = 16.87, P = 0.0002) difference was found in the recurrence rates: 59 recurrences/725 patients (or 8.1%) after 1 year, 89 recurrences/682 patients (or 13.0%) after 2 years and 98 recurrences/595 (or 16.4%) after 5 years. However, when subgrouping patients in three 24‐month subsets, the recurrence rates showed a steady and progressive decrease in the three biennia 2011–2012 (group A), 2013–2014 (group B) and 2015–2016 (group C) at 12‐, 48‐ and 60‐month follow‐ups. Recurrences after 12 months were 29/225 (12.9%), 19/285 (6.7%) and 11/215 (5.1%) (ꭓ2 = 8.53, P = 0.014) in groups A, B and C respectively; after 24 months, 36/226 (15.9%), 31/242 (12.8%) and 22/214 (10.2%) (ꭓ2 = 2.38, P = 0.30 N.S.) in groups A, B and C respectively; after 60 months, 38/194 (19.5%), 36/215 (16.7%) and 24/186 (12.9%) (ꭓ2 = 2.23, P = 0.32) in groups A, B and C respectively.

Conclusions

BPE is an effective, disease‐targeted, minimally invasive and inexpensive way to treat PD. Its results are influenced by the experience of the team involved, especially regarding early recurrences/failure of surgery. At least 5‐year follow‐ups are needed to ascertain the outcome of surgery for PD.
Has the Belt and Road Initiative Improved the Quality of Food Imported by Chinese Enterprises?
Authors: Zhou Kexuan , Kumar Sanjay , Lu Futao , Fang Qiaoyun , Yu Linhui
Published: March 2022

Using micro‐level data from 2009–2015 and the difference‐in‐difference method, this paper empirically examines the impact of the Belt and Road Initiative (BRI) on the quality of food imported by Chinese enterprises from BRI countries. Our baseline results show that the BRI significantly improved the quality of food imported from these countries. Further investigation reveals that trade patterns, ownership types, import regions, transportation methods, and product quality show significant heterogeneous effects in influencing the quality of imported food. A mechanism analysis indicates that the BRI improves the quality of imported food through three main channels: import trade environment enhancement, competition effect, and consumption upgrading, with the competition effect having the largest impact compared with the other two channels. Our findings suggest that China should not only improve the infrastructure in BRI countries but also use the BRI as an opportunity to enhance the level of cooperation with BRI countries and maintain stability and sustainability in cooperation with them.
Unexpected finding after aortic arch operation: a left ventricular pseudoaneurysm – Who is the culprit?
Authors: Denman Emily , Marvaki Apostolia , Huang Marilou , Lamas Sergio , Harrison James , Ammar Thoraya , Deshpande Ranjit , Monaghan Mark J , Papachristidis Alexandros
Published: March 2022

We present a case of a 61‐year‐old female who, after undergoing frozen elephant trunk surgery, was found to have an unexpected left ventricular pseudoaneurysm on transthoracic echocardiogram. The pseudoaneurysm was caused by the left ventricular vent catheter constantly impinging the LV wall of the beating heart during surgery. Contrast echocardiography, cardiac magnetic resonance imaging and computed tomography (CT) imaging confirmed the diagnosis and served for follow‐up demonstrating the narrow neck and outpouching structure on the apical lateral wall. The patient remains asymptomatic two years after the operation and is being followed up with echocardiography and CT imaging.
Aprotinin treatment against SARS‐CoV‐2: A randomized phase III study to evaluate the safety and efficacy of a pan‐protease inhibitor for moderate COVID‐19
Authors: Redondo‐Calvo Francisco Javier , Padín Juan Fernando , Muñoz‐Rodríguez José Ramón , Serrano‐Oviedo Leticia , López‐Juárez Pilar , Porras Leal María Lourdes , González Gasca Francisco Javier , Rodríguez Martínez Marta , Pérez Serrano Raúl , Sánchez Cadena Abraham , Bejarano‐Ramírez Natalia , Muñoz Hornero Constanza , Barberá Farré José Ramón , Domínguez‐Quesada Inmaculada , Sepúlveda Berrocal María A. , Villegas Fernández‐Infantes María  Dolores , Manrique Romo María Isabel , Parra Comino Ángel , Pérez‐Ortiz José Manuel , Gómez‐Romero Francisco Javier ,   ATAC team
Published: March 2022

Background

SARS‐CoV‐2 virus requires host proteases to cleave its spike protein to bind to its ACE2 target through a two‐step furin‐mediated entry mechanism. Aprotinin is a broad‐spectrum protease inhibitor that has been employed as antiviral drug for other human respiratory viruses. Also, it has important anti‐inflammatory properties for inhibiting the innate immunity contact system.

Methods

This was a multicentre, double‐blind, randomized trial performed in four Spanish hospitals comparing standard treatment versus standard treatment + aprotinin for patients with COVID‐19 between 20 May 2020 and 20 October 2021. The primary efficacy outcomes were length of hospital stay and ICU admission. The secondary endpoints were each of the primary efficacy outcomes and a composite of oxygen therapy, analytical parameters and death. Safety outcomes included adverse reactions to treatment during a 30‐day follow‐up period. Treatment was given for 11 days or till discharge.

Results

With almost identical analytical profiles, significant differences were observed in treatment time, which was 2 days lower in the aprotinin group (p = .002), and length of hospital admission, which was 5 days shorter in the aprotinin group (p = .003). The incidence of discharge was 2.19 times higher (HR: 2.188 [1.182–4.047]) in the aprotinin group than in the placebo group (p = .013). In addition, the aprotinin‐treated group required less oxygen therapy and had no adverse reactions or side effects.

Conclusion

Inhaled aprotinin may improve standard treatment and clinical outcomes in hospitalized patients with COVID‐19, resulting in a shorter treatment time and hospitalization compared with the placebo group. The administration of aprotinin was safe.
A possibility of error‐related processing contamination in the No‐go N2: The effect of partial‐error trials on response inhibition processing
Authors: Maruo Yuya , Masaki Hiroaki
Published: March 2022

This study investigated whether error‐related negativity (ERN) elicited by partial errors and No‐go N2 represent distinct or similar components. We also investigated whether the error positivity (Pe) and No‐go P3 represent distinct or similar components. Partial‐error trials are behaviourally classified as correct trials but preceded by covert muscular activities. Recent studies have reported that analysing partial‐error trials is useful for investigating the functional roles of ERN and No‐go N2. In this study, 23 participants performed a Go/No‐go flanker task. They performed nine blocks of 60 trials each. Stimulus‐locked event‐related potentials (ERPs) were averaged separately for Go‐congruent pure‐correct trials, Go‐incongruent pure‐correct trials and No‐go pure‐correct trials. In addition, we compared the stimulus‐locked ERPs among No‐go pure‐correct trials, No‐go partial‐error trials, Go‐incongruent pure‐correct trials and Go‐incongruent partial‐error trials. Electromyogram (EMG)‐locked ERPs were averaged separately for correct trials, overt errors in No‐go trials, partial errors in No‐go trials, overt errors in incongruent trials and partial errors in incongruent trials. N2 was remarkably larger in No‐go partial‐error trials than in No‐go pure‐correct trials. Consistent with previous findings, the No‐go partial‐error N2 might reflect error‐related processing. P3 amplitudes were larger in the No‐go trials than in both the Go‐congruent and Go‐incongruent trials. These results suggest that the No‐go P3, but not the No‐go N2, might reflect inhibition of overt movement. The present findings provide further evidence that the previously reported increase in No‐go N2 may be due to an overlap of the ERN elicited by partial errors.
Using magnetic resonance fingerprinting to characterize periventricular nodular heterotopias in pharmacoresistant epilepsy
Authors: Choi Joon Yul , Krishnan Balu , Hu Siyuan , Martinez David , Tang Yinging , Wang Xiaofeng , Sakaie Ken , Jones Stephen , Murakami Hiroatsu , Blümcke Ingmar , Najm Imad , Ma Dan , Wang Zhong Irene
Published: March 2022

Objective

We aimed to use a novel magnetic resonance fingerprinting (MRF) technique to examine in vivo tissue property characteristics of periventricular nodular heterotopia (PVNH). These characteristics were further correlated with stereotactic‐electroencephalographic (SEEG) ictal onset findings.

Methods

We included five patients with PVNH who had SEEG‐guided surgery and at least 1 year of seizure freedom or substantial seizure reduction. High‐resolution MRF scans were acquired at 3 T, generating three‐dimensional quantitative T1 and T2 maps. We assessed the differences between T1 and T2 values from the voxels in the nodules located in the SEEG‐defined seizure onset zone (SOZ) and non‐SOZ, on ‐individual and group levels. Receiver operating characteristic analyses were performed to obtain the optimal classification performance. Quantification of SEEG ictal onset signals from the nodules was performed by calculating power spectrum density (PSD). The association between PSD and T1/T2 values was further assessed at different frequency bands.

Results

Individual‐level analysis showed T1 was significantly higher in SOZ voxels than non‐SOZ voxels (p < .05), with an average 73% classification accuracy. Group‐level analysis also showed higher T1 was significantly associated with SOZ voxels (p < .001). At the optimal cutoff (normalized T1 of 1.1), a 76% accuracy for classifying SOZ nodules from non‐SOZ nodules was achieved. T1 values were significantly associated with ictal onset PSD at the ultraslow, θ, β, γ, and ripple bands (p < .05). T2 values were significantly associated with PSD only at the ultraslow band (p < .05).

Significance

Quantitative MRF measures, especially T1, can provide additional noninvasive information to separate nodules in SOZ and non‐SOZ. The T1 and T2 tissue property changes carry electrophysiological underpinnings relevant to the epilepsy, as shown by their significant positive associations with power changes during the SEEG seizure onset. The use of MRF as a supplementary noninvasive tool may improve presurgical evaluation for patients with PVNH and pharmacoresistant epilepsy.
Tobacco smoking and binge alcohol use are associated with incident venous thromboembolism in an HIV cohort
Authors: Luu Brandon , Ruderman Stephanie , Nance Robin , Delaney Joseph A. C. , Ma Jimmy , Hahn Andrew , Heckbert Susan R. , Budoff Matthew J. , Crothers Kristina , Mathews William C. , Christopolous Katerina , Hunt Peter W. , Eron Joseph , Moore Richard , Keruly Jeanne , Lober William B. , Burkholder Greer A. , Willig Amanda , Chander Geetanjali , McCaul Mary E. , Cropsey Karen , O'Cleirigh Conall , Peter Inga , Feinstein Matthew , Tsui Judith I. , Lindstroem Sara , Saag Michael , Kitahata Mari M. , Crane Heidi M. , Drumright Lydia N. , Whitney Bridget M.
Published: March 2022

Background

People with HIV (PWH) are at increased risk of cardiovascular comorbidities and substance use is a potential predisposing factor. We evaluated associations of tobacco smoking and alcohol use with venous thromboembolism (VTE) in PWH.

Methods

We assessed incident, centrally adjudicated VTE among 12 957 PWH within the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort between January 2009 and December 2018. Using separate Cox proportional hazards models, we evaluated associations of time‐updated alcohol and cigarette use with VTE, adjusting for demographic and clinical characteristics. Smoking was evaluated as pack‐years and never, former, or current use with current cigarettes per day. Alcohol use was parameterized using categorical and continuous alcohol use score, frequency of use, and binge frequency.

Results

During a median of 3.6 years of follow‐up, 213 PWH developed a VTE. One‐third of PWH reported binge drinking and 40% reported currently smoking. In adjusted analyses, risk of VTE was increased among both current (HR: 1.44, 95% CI: 1.02–2.03) and former (HR: 1.44, 95% CI: 0.99–2.07) smokers compared to PWH who never smoked. Additionally, total pack‐years among ever‐smokers (HR: 1.10 per 5 pack‐years; 95% CI: 1.03–1.18) was associated with incident VTE in a dose‐dependent manner. Frequency of binge drinking was associated with incident VTE (HR: 1.30 per 7 days/month, 95% CI: 1.11–1.52); however, alcohol use frequency was not. Severity of alcohol use was not significantly associated with VTE.

Conclusions

Current smoking and pack‐year smoking history were dose‐dependently associated with incident VTE among PWH in CNICS. Binge drinking was also associated with VTE. Interventions for smoking and binge drinking may decrease VTE risk among PWH.
A micro‐CT analysis of radicular dentine thickness in mandibular first premolars presenting C‐shaped root canals: Identification of potential danger zones
Authors: Sierra‐Cristancho Alfredo , González‐Osuna Luis , Balanta‐Melo Julián , Cafferata Emilio A. , Rojas Carolina , Melgar‐Rodríguez Samanta , Carvajal Paola , Vernal Rolando
Published: March 2022

Aim

To describe the radicular dentine thickness in mandibular first premolars presenting C‐shaped root canals, to identify the canal walls with less thickness as potential danger zones. In addition, to describe the internal and external anatomical characteristics of these teeth and associate them with the dentine thickness.

Methodology

A total of 70 mandibular first premolars presenting C‐shaped root canals were examined. Their internal morphology was analysed using Vertucci’s and Fan’s criteria, and their external morphology was analysed using the ASUDAS score. Besides, the dentine thickness around the root canals was two/three‐dimensionally determined at five root planes and quantified in the distal and the mesial aspects.

Results

According to Fan’s, ASUDAS, and Vertucci’s classifications, the most common canal configurations were category C3, grade 3, and type V, respectively. In Vertucci's type III anatomy, the mesial root wall of the lingual canal showed significantly less dentine thickness than the distal wall in the middle plane (p = .031). Similarly, in Vertucci's type V anatomy, significantly less dentine thickness was observed in the mesial root wall of the buccal and lingual canals in the middle plane (p < .001) and the buccal canal in the middle‐apical plane (p = .014) than the distal root wall of these canals. In teeth with ASUDAS grade 3 and 4 scores, significantly less dentine thickness was observed in the mesial in comparison with the distal root wall of these canals. These differences were demonstrated in the middle and middle‐apical planes (p < .001) of grade 3 teeth and the middle‐apical plane (p < .001) of grade 4 teeth. In these root planes, the Ver1‐AS3 and VerV‐AS3 combinations presented a 4‐times greater risk of presenting walls with a critical dentine thickness of 0.6 mm (odds ratio [OR] = 4, p = .025) than the combinations Ver1‐AS2, VerV‐AS2, VerV‐AS4, and VerIII‐AS3.

Conclusions

The root canal system configuration of mandibular first premolars with C‐shaped canals showed a wide range of anatomical variations. The lowest dentine thickness was located in the mesial wall of the canals in the middle and apical root thirds of Vertucci’s type III and V anatomies and in teeth with deep radicular grooves scored as ASUDAS grades 3 and 4. In the middle and middle‐apical planes, the presence of the combinations Ver1‐AS3 and VerV‐AS3 showed a high risk of presenting a critical dentine thickness of 0.6 mm. Therefore, these root canal walls with less dentine thickness represent potential instrumentation danger zones in mandibular first premolars with C‐shaped canals.
The role of heating rate on the sintering of glass powders
Authors: Stevens MacKenzie , Carty William M.
Published: March 2022

It is proposed that heating rate affects the apparent sintering temperatures of glass powders. The accumulation of thermal energy over time, or heat work (K s), is calculated over the range from the glass transition temperature to sintering temperature with the logarithm of time for heating rates from 1 to 60 K/min. The required heat work is independent of heating rate for two silicate glass powders but shows a decreasing heat work requirement for increasing heating rates for a borosilicate glass powder. Small cylindrical powder compact samples were used to minimize heat‐transfer problems and were observed thermoanalytically using a hot‐stage microscope. The densification temperature, defined as the peak in the shrinkage versus temperature curve, increases with increasing heating rate and is sensitive to the initial compact density. The use of mechanically pressed compacts with similar compact densities minimizes the contribution of initial density, allowing the comparison of sintering behavior as a function of heating rate.
Bread‐making performance of wheat flours enriched with vital gluten treated with non‐thermal plasma
Authors: Barros Jefferson Henrique Tiago , Ribeiro Vitor Anselmo da Guia , Ferreira Mariana de Paula Kraüss , Steel Caroline Joy
Published: March 2022

Vital gluten (VG) is a food ingredient commonly used in bread making, and its quality varies according to its obtainment process. The objective of this study was to verify the performance of VG treated with non‐thermal plasma (NTP) at 50 and 150 W and 5 L/min of argon gas as an enhancing ingredient for weak or diluted wheat flour. Quality analyses were performed on dough and bread. Farinographic and alveographic data revealed that VG treatment at 50 W increased the development time (13.49% and 5.80%), stability (9.67% and 0%), tenacity (19.98% and 22.51%) and flour strength (30.48% and 27.13%) in doughs containing 14% and 16% protein respectively. Breads prepared with these flours demonstrated an increase in specific volume by 11.70% and 10.05%, and in the number of alveoli by 5.19% and 15.22% respectively. We concluded that NTP used under adequate conditions can positively modulate the functionality of VG.
In vitro and in vivo antithrombotic and antioxidant properties of microencapsulated brewers’ spent grain peptides
Authors: Cian Raúl E. , Oliva María E. , Garzón Antonela G. , Ferreira María del Rosario , D´Alessandro María E. , Drago Silvina R.
Published: March 2022

Antioxidant and antithrombotic activities of microencapsulated brewers’ spent grain peptides (BSGH‐C) after simulated gastrointestinal digestion (SGID) and the in vivo properties using a model of growing Wistar rats fed with sucrose‐rich diet (SRD) were determined. Microencapsulation reduced the cleavage of peptides (66.5 vs. 39.2%), partially preserved the in vitro antioxidant activity (ABTS+ inhibition and FRAP) and reduced the in vitro antithrombotic activity. SRD diet produced a pro‐oxidant and pro‐thrombotic systemic environment in rats, which was reversed by the consumption of BSGH‐C. A positive correlation between in vitro antioxidant and antithrombotic activity of BSGH‐C after SGID with the respective in vivo effects observed in rats fed BSGH‐C (r = 0.9997 and r = 0.9411, respectively) was established. The goodness of both, the in vitro models determining bioactive properties after SGID, and the microencapsulation protecting the peptides from gastrointestinal environment were demonstrated. Thus, it was possible to produce microcapsules with bioavailable bioactive BSG peptides.
Effects of wheat flour supplemented with soy protein concentrate on the rheology, microstructure and water mobility of protein‐fortified precooked noodles
Authors: Yoon Seong , Yang Geunhyuk , Kwon Hyukjin , Lee Suyong
Published: March 2022

Wheat flour was supplemented with different levels of soy protein concentrate (SPC) and applied to precooked noodles for protein fortification whose quality attributes were characterised in terms of rheology, microstructure and water mobility. The wheat flours with high levels of SPC showed lower enthalpy values and higher temperatures derived from starch gelatinisation. They also exhibited lower values of the pasting viscosity and dynamic viscoelastic parameters. The mixolab measurements demonstrated that the supplement with SPC was effective in raising the water absorption and dough stability of wheat flour. In addition, the use of SPC‐supplemented wheat flours produced precooked noodles with tight and dense structures, which were confirmed by scanning electron microscopic analysis. These microstructural changes were consequently related to higher maximum resistance to extension and lower extensibility of the noodles. However, the SPC‐supplemented wheat flours did not significantly affect the cooking loss of the noodles. Furthermore, three water components with different mobility were observed in the precooked noodles whose spin‐spin relaxation times were distinctly reduced with increasing levels of SPC. Overall similarities in the sensory noodle attributes were detected as wheat flour was supplemented with SPC at a level of 8% (w/w).
Real‐world efficacy and safety of dupilumab in Chinese patients with atopic dermatitis: a single‐centre, prospective, open‐label study
Authors: Gu C. , Wu Y. , Luo Y. , Wang S. , Yin H. , Gao Y. , Wang C. , Yao X. , Li W.
Published: March 2022

Background

Dupilumab, an antibody against interleukin‐4 receptor α, has demonstrated elegant efficacy and safety profiles in patients with moderate‐to‐severe atopic dermatitis (AD). However, the efficacy of dupilumab varies among AD patients, and compared with the Caucasian population, the data of dupilumab for Asian people, especially Chinese AD patients, is very limited.

Objective

To investigate the efficacy and safety of dupilumab for AD in a real‐world Chinese single‐centre prospective cohort.

Methods

We enrolled 138 moderate‐to‐severe AD patients receiving dupilumab treatment at Huashan Hospital, Shanghai, China in this 16‐week, single‐centre, prospective, open‐label study. The patients were evaluated at baseline, 2, 4, 8 and 16 weeks after first dupilumab administration for multiple physician‐ and patient‐reported outcome measures. Blood eosinophil counts and total serum IgE were measured.

Results

There were early and sustained improvement in all the efficacy measures evaluated after dupilumab administration. 64.5% AD patients achieved an improvement of ≥75% in the Eczema Area and Severity Index from baseline, and 60.9% patients achieved the Investigator's Global Assessment 0/1 (or a reduction of ≥2 points from baseline) at week 16. The trunk demonstrated the most significantly decreased efficacy score [median decreased 96.24% (interquartile range, 89.04 to 100%)] compared with other body sites. Female (adjusted OR: 2.12, 95% confidence interval: 0.79–5.74) and body mass index (BMI) <24 (3.03; 1.19–7.68) were identified as potential predictive factors of good response; while age >60 (0.57; 0.10–3.28) predicted poor response. Adverse events were reported by 34.1% patients, and facial erythema (13%) and ocular symptoms (10.9%) were the most common.

Conclusions

Dupilumab demonstrated favourable efficacy and well‐tolerated safety in Chinese AD patients in real‐world practice.