bluuebunny/crossref_metadata_2025 huggingface dataset:
Subunit cooperation in the Get1/2 receptor promotes tail-anchored membrane protein insertion
Authors: Chio Un Seng , Liu Yumeng , Chung SangYoon , Shim Woo Jun , Chandrasekar Sowmya , Weiss Shimon , Shan Shu-ou
Published: October 2021

The guided entry of tail-anchored protein (GET) pathway, in which the Get3 ATPase delivers an essential class of tail-anchored membrane proteins (TAs) to the Get1/2 receptor at the endoplasmic reticulum, provides a conserved mechanism for TA biogenesis in eukaryotic cells. The membrane-associated events of this pathway remain poorly understood. Here we show that complex assembly between the cytosolic domains (CDs) of Get1 and Get2 strongly enhances the affinity of the individual subunits for Get3•TA, thus enabling efficient capture of the targeting complex. In addition to the known role of Get1CD in remodeling Get3 conformation, two molecular recognition features (MoRFs) in Get2CD induce Get3 opening, and both subunits are required for optimal TA release from Get3. Mutation of the MoRFs attenuates TA insertion into the ER in vivo. Our results demonstrate extensive cooperation between the Get1/2 receptor subunits in the capture and remodeling of the targeting complex, and emphasize the role of MoRFs in receptor function during membrane protein biogenesis.
Cyberattacks, cyber threats, and attitudes toward cybersecurity policies
Authors: Snider Keren L G , Shandler Ryan , Zandani Shay , Canetti Daphna
Published: October 2021

Does exposure to cyberattacks influence public support for intrusive cybersecurity policies? How do perceptions of cyber threats mediate this relationship? While past research has demonstrated how exposure to cyberattacks affects political attitudes, the mediating role played by threat perception has been overlooked. This study employs a controlled randomized survey experiment design to test the effect of exposure to lethal and nonlethal cyberattacks on support for different types of cybersecurity policies. One thousand twenty-two Israeli participants are exposed to scripted and simulated television reports of lethal or nonlethal cyberattacks against national infrastructure. Findings suggest that exposure to cyberattacks leads to greater support for stringent cybersecurity regulations, through a mechanism of threat perception. Results also indicate that different types of exposure relate to heightened support for different types of regulatory policies. People exposed to lethal cyberattacks tend to support cybersecurity policies that compel the government to alert citizens about cyberattacks. People who were exposed to nonlethal attacks, on the other hand, tend to support oversight policies at higher levels. More broadly, our research suggests that peoples’ willingness to accept government cybersecurity policies that limit personal civil liberties and privacy depends on the type of cyberattacks to which they were exposed and the perceptions associated with such exposure.
Fiscal capacity in ‘‘responsible government’’ colonies: the Cape Colony in comparative perspective, c. 1865–1910
Authors: Gwaindepi Abel
Published: October 2021

This study contributes to debates on the efficacy of institutions in settler colonies by comparing the Cape Colony’s fiscal path to the experiences of Australia, New Zealand, and Canada. I find that the Cape’s fiscal trajectory was divergent. Agricultural and mining taxes were important surrogates of income taxes in other colonies, but the Cape’s narrow interests pushed for insulation from direct taxes. This made the Cape’s fiscal path unsustainable with comparatively low per capita taxes, high deficits, and the highest level of indebtedness. I argue that the instrumentality of ‘‘responsible government” status was conditional on how imported self-government institutions were endogenized.
The Association of Nε-Carboxymethyllysine With Polyunsaturated and Saturated Fatty Acids in Healthy Individuals
Authors: Deo Permal , Dhillon Varinderpal S , Thomas Philip , Fenech Michael
Published: October 2021

Red blood cell (RBC) fatty acid status is used as a biomarker of dietary intake of fats; however, there is still a paucity of evidence regarding individual fatty acids and modulation of endogenous advanced glycation end product (AGE) levels. Due to membrane polyunsaturated fatty acid (PUFA) being a well-known target for peroxidation, we hypothesized that cellular PUFAs are positively associated with circulatory Nε-carboxymethyllysine (CML) that is also influenced by glyoxal levels in healthy cohorts. To test this, we investigated the association between RBC fatty acids and circulatory AGE biomarkers in healthy individuals. The results showed a negative association between saturated fatty acids (SFA) and CML, and stepwise multivariate regression analysis indicated that stearic acid was negatively associated with CML levels (β = −0.200, p = .008) after adjusting for age, body mass index (BMI), and gender. In addition, stearic acid:palmitic acid ratio was also negatively correlated with plasma concentrations of CML (rp = −.191, p = .012) and glucose (rp = −.288, p = .0001). PUFAs showed a positive association with CML levels, particularly docosapentaenoic acid, γ-linolenic acid, arachidonic acid, and docosadienoic acid. However, these associations were not evident after the multiple regression analysis adjusted for age, BMI, and gender. A strong negative correlation (rp = −.98, p < .0001) between total PUFA and total SFA was observed. Furthermore, the SFA:PUFA ratio was inversely correlated with CML (rp = −.227, p < .003). Overall, this study indicates that different fats and their combinations may influence the formation of AGEs and that carefully controlled interventions are required to further test this hypothesis.
Emotional Appeals, Climate Change, and Young Adults: A Direct Replication of Skurka et al. (2018)
Authors: Skurka Chris , Romero-Canyas Rainer , Joo Helen H , Acup David , Niederdeppe Jeff
Published: October 2021

There is much need to verify the robustness of published findings in the field of communication—particularly regarding the effects of persuasive emotional appeals about social issues. To this end, we present the results from a preregistered, direct replication of C. Skurka, J. Niederdeppe, R. Romero-Canyas, and D. Acup (2018). The original study found that a threat appeal about climate change can increase risk perception and activism intentions and that a humor appeal can also increase activism intentions with a large sample of young adults. Using the same stimuli, measures, and experimental design with a similar sample, we fail to replicate these main effects. We do, however, replicate age as a moderator of humor’s effect on perceived risk, such that the humor appeal only persuaded emerging adults (ages 18–21.9). We consider several explanations for our discrepant findings, including the challenges (and opportunities) that persuasion researchers must navigate when communicating about rapidly evolving social issues.
Deep learning models in detection of dietary supplement adverse event signals from Twitter
Authors: Wang Yefeng , Zhao Yunpeng , Schutte Dalton , Bian Jiang , Zhang Rui
Published: October 2021

Objective

The objective of this study is to develop a deep learning pipeline to detect signals on dietary supplement-related adverse events (DS AEs) from Twitter.

Materials and Methods

We obtained 247 807 tweets ranging from 2012 to 2018 that mentioned both DS and AE. We designed a tailor-made annotation guideline for DS AEs and annotated biomedical entities and relations on 2000 tweets. For the concept extraction task, we fine-tuned and compared the performance of BioClinical-BERT, PubMedBERT, ELECTRA, RoBERTa, and DeBERTa models with a CRF classifier. For the relation extraction task, we fine-tuned and compared BERT models to BioClinical-BERT, PubMedBERT, RoBERTa, and DeBERTa models. We chose the best-performing models in each task to assemble an end-to-end deep learning pipeline to detect DS AE signals and compared the results to the known DS AEs from a DS knowledge base (ie, iDISK).

Results

DeBERTa-CRF model outperformed other models in the concept extraction task, scoring a lenient microaveraged F1 score of 0.866. RoBERTa model outperformed other models in the relation extraction task, scoring a lenient microaveraged F1 score of 0.788. The end-to-end pipeline built on these 2 models was able to extract DS indication and DS AEs with a lenient microaveraged F1 score of 0.666.

Conclusion

We have developed a deep learning pipeline that can detect DS AE signals from Twitter. We have found DS AEs that were not recorded in an existing knowledge base (iDISK) and our proposed pipeline can as sist DS AE pharmacovigilance.
The influence of integrating clinical practice guideline order bundles into a general admission order set on guideline adoption
Authors: Mrosak Justine , Kandaswamy Swaminathan , Stokes Claire , Roth David , Dave Ishaan , Gillespie Scott , Orenstein Evan
Published: October 2021

Objectives of this study were to (1) describe barriers to using clinical practice guideline (CPG) admission order sets in a pediatric hospital and (2) determine if integrating CPG order bundles into a general admission order set increases adoption of CPG-recommended orders compared to standalone CPG order sets. We identified CPG-eligible encounters and surveyed admitting physicians to understand reasons for not using the associated CPG order set. We then integrated CPG order bundles into a general admission order set and evaluated effectiveness through summative usability testing in a simulated environment. The most common reasons for the nonuse of CPG order sets were lack of awareness or forgetting about the CPG order set. In usability testing, CPG order bundle use increased from 27.8% to 66.6% while antibiotic ordering errors decreased from 62.9% to 18.5% with the new design. Integrating CPG-related order bundles into a general admission order set improves CPG order set use in simulation by addressing the most common barriers to CPG adoption.
109 Diet-induced Clinical Responsiveness of Translational Dog Model for Human Western Diet (WD)-related Disease Research
Authors: Iennarella-Servantez Chelsea A , Kathrani Aarti , Sahoo Dipak , Long Elizabeth , Zdyrski Christopher , Gabriel Vojtech , Mao Sichao , Bourgois-Mochel Agnes , Resop Mara , Rund Lili , Rossoni-Serao Mariana C , Jergens Albert , Mochel Jonathan , Allenspach Karin
Published: October 2021

Human consumption of Western diets (WD) has been strongly associated with increased central obesity, adipocyte hypertrophy, intestinal epithelial stemness/proliferation, dyslipidemia, and blood pressure. These changes reflect metabolic dysfunction and contribute to increased risk of type 2 diabetes mellitus and colorectal cancer. As comprehensive molecular/clinical comparisons have not been performed, the objective of this study was to evaluate diet-induced changes in dogs as a clinically-responsive model for human WD-related disease research. Methods: In a crossover design, 10 dogs were fed either a 1.) control diet (CON) formulated based on the Acceptable Macronutrient Distribution Ranges and fiber recommendations for humans; or 2.) Western diet (WD) formulated based on National Health and Nutrition Examination Survey dataset parameters. Diets were prepared cooked with the same ingredients and formulated to meet/exceed nutrient/energy requirements for both humans/dogs and fed isocalorically based on calculated metabolizable energy (ME). Following each period (~7–8 weeks), experimental parameters were measured. Results/Conclusions: Mean body weights were 8.83 and 9.28kg for CON and WD diets, respectively (P = 0.0018). Fasted (10-hour) blood samples differed significantly (P < 0.01) for mean fasting bile acids (CON=0.79, WD=8.94μmol/L), serum triglycerides (CON=45.70, WD=67.80mg/dL), and serum cholesterol (CON=140.10, WD=175.40mg/dL) demonstrating diet-dependent alterations in lipid profiles. Mean systolic blood pressures were 131.66 and 140.02mmHg for CON and WD, respectively (P < 0.0001). Histological analysis revealed diet-dependent changes in colonic epithelial villus height (CON=182, WD=207μm) and villus:crypt ratio (CON=2.61, WD=3.89). Preliminary RNA-ISH analysis (n = 3 dogs) showed increased LGR5+ expression (intestinal stem-cell marker) in WD compared to CON group (P = 0.0019) suggesting an increased “stemnness” of colonic epithelium. Further, mean adipocyte diameters were increased in omental fat biopsies (CON=58.6, WD=62.5μm; P < 0.0001) but not subcutaneous fat biopsies (P >0.05) following WD feeding, consistent with centralized obesity. Collectively, these results demonstrate effects of diet-induced changes in dogs as a clinically-responsive model for human WD-related disease research.
233 Estrus Response and Pregnancy Rates of Beef Replacement Heifers Enrolled in Two Fixed-time Artificial Insemination Protocols, with or Without Pre-synchronization
Authors: Mercadante Vitor R G Rodrigues Gomes , Lamb G Cliff C , Oosthuizen Nicky , Wege Dias Nicholas W , Pancini Stefania , Haines Hannah , Currin John , Clark Sherrie , Stewart Jamie L , Pent Gabriel J , Holton Matthew P , Davis Dylan B , Hernandez Shane R R , Stewart R Lawton , Fontes Pedro L
Published: October 2021

Pre-synchronization strategies with prolonged exposure to exogenous progesterone have the potential to alter estrus expression and improve fertility in replacement beef heifers. The objective of this study was to evaluate the estrus response and pregnancy rate of beef heifers enrolled in two fixed-time artificial insemination (TAI) protocols. A total of 306 heifers (14 ± 2 months of age; 372 ± 24 kg body weight [BW]) at three locations were enrolled in the study. Within location, heifers were stratified by age and BW and randomly assigned to one of two treatments: 1) PG-CIDR54 (n = 152), heifers were administered prostaglandin F2α (PGF; 25 mg) and a controlled internal drug releasing (CIDR) insert (Day -14), an injection of GnRH [100 μg (Day -7)], PGF injection and CIDR removal (Day 0), and a second injection of GnRH concurrently with TAI 54 ± 2 h later (Day 2); 2) 7-day CO-Synch+CIDR (CTRL; n = 154), heifers were administered GnRH (100 μg) and a CIDR insert (Day -7), PGF (25 mg) injection and CIDR removal (Day 0), and a second injection of GnRH concurrently with TAI 54 ± 2 h later (Day 2). All heifers received an estrus alert patch on Day 0 and were evaluated for patch activation at TAI on Day 2. Pregnancy was diagnosed by transrectal ultrasonography between 35 and 55 days after TAI. The percentage of heifers exhibiting estrus between Day 0 and 2 was greater (P < 0.01) in PG-CIDR54 compared with CTRL (77.0 and 39.6%, respectively). In addition, pregnancy rate to TAI tended (P = 0.08) to be greater for PG-CIDR54 compared with CTRL (48.0 and 38.3%, respectively). We conclude that beef heifers enrolled in the PG-CIDR54 protocol had increased estrus expression and tended to have greater pregnancy rate when compared with heifers enrolled in the 7-day CO-Synch+CIDR protocol.
Patients’ Access to Telephone and E-mail Services Provided by IBD Nurses in Canada
Authors: Chauhan Usha , Stitt Larry , Rohatinsky Noelle , Watson Melanie , Currie Barbara , Westin Lisa , McCaw Wendy , Norton Christine , Nistor Irina
Published: October 2021

Background

Inflammatory bowel disease (IBD) can impact the quality of life and increase health care resource utilization. Nurses play an integral role in ensuring ease of access to care between scheduled office visits.

Aims

This study aimed to capture the utilization of Canadian IBD nursing telephone and e-mail services.

Methods

A descriptive cross-sectional study with an eight-item online survey was completed by nurses to assess the use of nurse-led telephone and e-mail services for IBD patients.

Results

Twenty-one IBD nurses participated, and 572 patients nurse encounters were reported. Patients with ulcerative (UC) contacted with disease flare when compared to Crohn’s disease (CD) (40% versus 24%, P < 0.001). Nursing services were primarily utilized for queries regarding medication (39.3%), disease exacerbations (29.6%), investigations (26%), and scheduling appointments (17.6%). Patients with CD had more telephone conversations (62.7%) and required more follow-up telephone calls (72.2%) compared to patients with UC (33%) and 25%, respectively. Nurse-managed interventions were provided independently for 61.4% of encounters, while 19% required a scheduled appointment in the IBD clinic. In the absence of telephone or e-mail assistance, older patients were more likely to call their family doctor (r = 0.18, P < 0.001), visit the emergency room (r = 0.18, P < 0.001), visit an urgent access clinic (r = 0.22, P < 0.001), or visit a walk-in clinic (r = 0.29, P < 0.001) than younger patients.

Conclusions

Nurse-managed IBD advice lines are proactive services that can address most patient disease-related concerns.
Validation of the Dutch version of the Hip Outcome Score; validity, reliability, and responsiveness in patients with femoroacetabular impingement syndrome
Authors: Röling Maarten A , Hesseling Brechtje , Jansen Sebastiaan P L , Bloem Rolf M , Mathijssen Nina M C
Published: October 2021

Due to a lack of a validated Dutch version of the Hip Outcome Score (HOS) considering functional outcome after hip arthroscopy for femoroacetabular impingement syndrome, we validated the Dutch version of the HOS (HOS-NL) in patients with femoroacetabular impingement syndrome for reliability, internal consistency, construct- and content validity. Furthermore, the smallest detectable change (SDC) and minimal clinically important difference (MCID) were determined. All consecutive patients scheduled for an arthroscopic procedure for FAIS were selected. Five questionnaires covering groin and hip pain were filled in at three moments in time (two pre-operatively with a maximum two-week interval and 6 months postoperatively). Main endpoints were reliability (test re-test, SDC), internal consistency (Cronbach alpha), construct validity (construct validity was considered sufficient if a least 75% of a-priori made hypotheses were confirmed), content validity (floor and ceiling effects) and responsiveness (MCID). The intraclass correlation coefficient (ICC) was 0.86 for the HOS ADL-NL and 0.81 for the HOS Sports-NL. SDC for the HOS ADL-NL was 21 and for the HOS Sports-NL 29 Cronbach alpha score was 0.882 for HOS ADL-NL and 0.792 for HOS Sports-NL. Construct validity was considered sufficient since 91% of the hypotheses were confirmed. No floor effects were determined. A small ceiling effect was determined for the HOS AD-NL postoperatively. The MCID for HOS ADL-NL and HOS Sports-NL were 14 and 11.0, respectively. The HOS-NL is a reliable and valid patient reported outcome measure for measuring physical function and outcome in active and young patients with femoroacetabular impingement syndrome.
Acute abdomen during pregnancy: appendicular deciduosis—a case report
Authors: Ghannouchi Mossaab , Nacef Karim , KHlifa Mohamed Ben , Iyed Kraim , Boudokhan Moez , Toumi Dhekra , Zoukar Olfa
Published: October 2021

Despite the fact that it is rarely found in the appendix during pregnancy, ectopic decidua can, in some cases, cause the occlusion of the appendicular lumen by extrinsic compression due to the expansion of endometrial tissue or due to decidua polyp formation. This condition consequently leads to appendicular inflammation. We report the case of a 27-year-old primigravida woman, 32 weeks of gestation, who presented to our facility with a 2-day history of isolated right iliac fossa pain. The diagnosis of an acute appendicitis was suspected and a planned appendectomy was performed. Microscopical examination showed appendicular deciduosis.
Identification of five important genes to predict glioblastoma subtypes
Authors: Tang Yang , Qazi Maleeha A , Brown Kevin R , Mikolajewicz Nicholas , Moffat Jason , Singh Sheila K , McNicholas Paul D
Published: October 2021

Background

Glioblastoma (GBM), the most common and aggressive primary brain tumour in adults, has been classified into three subtypes: classical, mesenchymal, and proneural. While the original classification relied on an 840 gene-set, further clarification on true GBM subtypes uses a 150-gene signature to accurately classify GBM into the three subtypes. We hypothesized whether a machine learning approach could be used to identify a smaller gene-set to accurately predict GBM subtype.

Methods

Using a supervised machine learning approach, extreme gradient boosting (XGBoost), we developed a classifier to predict the three subtypes of glioblastoma (GBM): classical, mesenchymal, and proneural. We tested the classifier on in-house GBM tissue, cell lines, and xenograft samples to predict their subtype.

Results

We identified the five most important genes for characterizing the three subtypes based on genes that often exhibited high Importance Scores in our XGBoost analyses. On average, this approach achieved 80.12% accuracy in predicting these three subtypes of GBM. Furthermore, we applied our five-gene classifier to successfully predict the subtype of GBM samples at our centre.

Conclusion

Our 5-gene set classifier is the smallest classifier to date that can predict GBM subtypes with high accuracy, which could facilitate the future development of a five-gene subtype diagnostic biomarker for routine assays in GBM samples.
Incidence, aetiology, and enviromental risk factors of community-acquired pneumonia requiring hospitalization in China: a 3-year, prospective, age-stratified, multi-centre case-control study
Authors: Qin Tian , Zhou Haijian , Ren Hongyu , Meng Jiantong , Du Yinju , Mahemut Mahemut , Wang Peng , Luo Nana , Tian Fei , Li Ming , Zhou Pu , Li Fang , Duan Pengyuan , Li Yinan , Zhao Na , Yuan Qiwu , Zhang Jinzhong , Cheng Lihong , Luo Longze , Fang Ming , Huang Xin , Gu Changguo , Zhou Huifang , Yang Min , Lu Shan , Jiang Xiangkun , Lin Hualiang , Tian Huaiyu , Kan Biao , Xu Jianguo
Published: October 2021

Background

Community-acquired pneumonia (CAP) is a leading infectious cause of hospitalisation and death worldwide. The knowledge about the incidence and aetiology of CAP in China was fragmented.

Methods

A multicenter study performed at four hospitals in four regions in China and clinical samples from CAP patients were collected and used for pathogen identification from July 2016 to June 2019.

Results

A total of 1,674 patients were enrolled and the average annual incidence of hospitalized CAP was 18.7 cases per 10,000 people (95% confidence interval 18.5–19.0). The most common viral and bacterial agents found in patients were respiratory syncytial virus (19.2%) and Streptococcus pneumoniae (9.3%). The co-infections percentage was 13.8%. Pathogen distribution displayed variations within age groups, and seasonal and regional differences. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was not detected. Respiratory virus detection was significantly positively correlated with air pollutants, including PM2.5, PM10, NO2 and SO2; and significantly negatively correlated with ambient temperature and O3 content; bacteria detection was opposite.

Conclusion

The hospitalized CAP incidence in China was higher than previously known. CAP etiology showed differences in age, seasons, regions, and respiratory viruses were detected at a higher rate than bacterial infection overall. Air pollutants and temperature have influence on the detection of pathogens.
SARS-CoV-2 Blood RNA Load Predicts Outcome in Critically Ill COVID-19 Patients
Authors: Heinrich Fabian , Nentwich Michael F , Bibiza-Freiwald Eric , Nörz Dominik , Roedl Kevin , Christner Martin , Hoffmann Armin , Olearo Flaminia , Kluge Stefan , Aepfelbacher Martin , Wichmann Dominic , Lütgehetmann Marc , Pfefferle Susanne
Published: October 2021

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA loads in patient specimens may act as a clinical outcome predictor in critically ill patients with coronavirus disease 2019 (COVID-19).

Methods

We evaluated the predictive value of viral RNA loads and courses in the blood compared with the upper and lower respiratory tract loads of critically ill COVID-19 patients. Daily specimen collection and viral RNA quantification by reverse transcription quantitative polymerase chain reaction were performed in all consecutive 170 COVID-19 patients between March 2020 and February 2021 during the entire intensive care unit (ICU) stay (4145 samples analyzed). Patients were grouped according to their 90-day outcome as survivors (n=100) or nonsurvivors (n=70).

Results

In nonsurvivors, blood SARS-CoV-2 RNA loads were significantly higher at the time of admission to the ICU (P=.0009). Failure of blood RNA clearance was observed in 33/50 (66%) of the nonsurvivors compared with 12/64 (19%) survivors (P<.0001). As determined by multivariate analysis, taking sociodemographic and clinical parameters into account, blood SARS-CoV-2 RNA load represents a valid and independent predictor of outcome in critically ill COVID-19 patients (odds ratio [OR; log10], 0.23; 95% CI, 0.12–0.42; P<.0001), with a significantly higher effect for survival compared with respiratory tract SARS-CoV-2 RNA loads (OR [log10], 0.75; 95% CI, 0.66–0.85; P<.0001). Blood RNA loads exceeding 2.51×103 SARS-CoV-2 RNA copies/mL were found to indicate a 50% probability of death. Consistently, 29/33 (88%) nonsurvivors with failure of virus clearance exceeded this cutoff value constantly.

Conclusions

Blood SARS-CoV-2 load is an important independent outcome predictor and should be further evaluated for treatment allocation and patient monitoring.
Carbon dioxide responsiveness mitigates rice yield loss under high night temperature
Authors: Bahuguna Rajeev Nayan , Chaturvedi Ashish Kumar , Pal Madan , Viswanathan Chinnusamy , Jagadish S V Krishna , Pareek Ashwani
Published: October 2021

Increasing night-time temperatures are a major threat to sustaining global rice (Oryza sativa L.) production. A simultaneous increase in [CO2] will lead to an inevitable interaction between elevated [CO2] (e[CO2]) and high night temperature (HNT) under current and future climates. Here, we conducted field experiments to identify [CO2] responsiveness from a diverse indica panel comprising 194 genotypes under different planting geometries in 2016. Twenty-three different genotypes were tested under different planting geometries and e[CO2] using a free-air [CO2] enrichment facility in 2017. The most promising genotypes and positive and negative controls were tested under HNT and e[CO2] + HNT in 2018. [CO2] responsiveness, measured as a composite response index on different yield components, grain yield, and photosynthesis, revealed a strong relationship (R2 = 0.71) between low planting density and e[CO2]. The most promising genotypes revealed significantly lower (P < 0.001) impact of HNT in high [CO2] responsive (HCR) genotypes compared to the least [CO2] responsive genotype. [CO2] responsiveness was the major driver determining grain yield and related components in HCR genotypes with a negligible yield loss under HNT. A systematic investigation highlighted that active selection and breeding for [CO2] responsiveness can lead to maintained carbon balance and compensate for HNT-induced yield losses in rice and potentially other C3 crops under current and future warmer climates.
Flexible learner or imposter? Learning A Level mathematics in England through the COVID-19 pandemic
Authors: Golding Jennie
Published: October 2021

We evidence English teacher and student perspectives on the learning of pre-university mathematics ‘A Level’ courses through the pandemic period to July 2021. Data are drawn from a 2017–21 classroom-close study of enactment of such courses in 13 fairly representative centres, using an institutional ethnographic approach. The pandemic picture was generally one of the significant and sustained negative impacts, though over the course of the study, respondents reported progress in addressing early limitations in the harnessing of digital platforms for learning. A small number of participating students reported home-based study beneficial for their mathematics learning, and a bigger group identified some wider benefits that partly offset the challenges. Most participating 16–18-year-old students, though, reported finding remote learning of mathematics both demanding and limiting. Pandemic constraints impacted most strongly on opportunities to engage with newer emphases within A Level courses: problem solving, reasoning, modelling, statistics and mechanics. Receiving academics reported that mathematical preparedness, and confidence, for mathematics-intense university courses has also been widely affected, with a bigger range of preparedness and confidence than usual. The study draws attention to the importance of studying subject-specific impact and drawing on student as well as teacher perceptions. It exposes a range of consequences of the cancellation of examinations and a need to develop and share effective pedagogies for working remotely with pre-university students.
Turner syndrome mosaicism: Challenges in identification and management in primary care
Authors: Bryant Pamela H. , Jacoby Delwin , Bunch Miriam , Speck Patricia M.
Published: October 2021

The spectrum of Turner syndrome (TS) includes Turner syndrome mosaicism (TSM), which is typically a nonhereditary chromosomal abnormality. Turner syndrome mosaicism presents uncommonly to primary care providers (PCPs), who often fail to recognize the subtle signs. The average age at diagnosis for common TS and TSM karyotype is 5.4 years, averaging 7.3 years. Often genetic confirmation, management, and recommended surveillance are delayed. Oftentimes, the PCP suspects a genetic etiology of an unusual phenotype, such as pinna placement or other unusual ear configurations, webbed neck with low posterior hairline, wide-spaced nipples, or short stature among other presentations. The PCP or geneticist orders diagnostic studies to confirm the diagnosis, such as a karyotype. After diagnosis, the PCP refers to the geneticist who initiates surveillance and makes recommendations for management. There are potential neurocognitive, cardiovascular, renal, reproductive, and endocrine issues. Treatment literature is vague and parental concerns are linked to quality mental health and quality of life for the family member with TS or TSM. The purpose of this article was to use a case study to introduce the topic of TS and TSM and to assist the PCP in the identification and management of patient and family concerns.
Systematic Curriculum Mapping of Virtual Patient Assignments to End-of-Program Outcomes
Authors: Altmiller Gerry , Alexy Eileen , Dzubaty Dolores , Jakubowski Tami , Kartoz Connie R.
Published: October 2021

Background:

During the COVID-19 pandemic, virtual clinical learning assignments replaced onsite clinical instruction in many prelicensure nursing programs, but the alignment of those learning experiences to end-of-program outcomes was unknown.

Purpose:

This article describes the process and results of mapping student competencies gained via virtual patient simulation experiences to a program's end-of-program outcomes and accrediting standards.

Methods:

A faculty team followed the process of curriculum mapping as described in the literature to evaluate the effectiveness of the program's virtual clinical learning product in addressing end-of-program outcomes.

Results:

The mapping process identified where competencies were being met, which needed enhancing or were redundant, and where gaps existed.

Conclusions:

Curriculum mapping is an effective strategy in evaluating whether virtual patient simulation learning experiences support end-of-program outcomes. Mapping learning activities to outcomes will be fundamental to curriculum development and evaluation as schools of nursing integrate accrediting standards.
Outcomes Associated With Early RBC Transfusion in Pediatric Severe Sepsis: A Propensity-Adjusted Multicenter Cohort Study
Authors: Muszynski Jennifer A. , Banks Russell , Reeder Ron W. , Hall Mark W. , Berg Robert A. , Zuppa Athena , Shanley Thomas P. , Cornell Timothy T. , Newth Christopher J. L. , Pollack Murray M. , Wessel David , Doctor Allan , Lin John C. , Harrison Rick E. , Meert Kathleen L. , Dean J. Michael , Holubkov Richard , Carcillo Joseph A.
Published: October 2021

Background:

Little is known about the epidemiology of and outcomes related to red blood cell (RBC) transfusion in septic children across multiple centers. We performed propensity-adjusted secondary analyses of the Biomarker Phenotyping of Pediatric Sepsis and Multiple Organ Failure (PHENOMS) study to test the hypothesis that early RBC transfusion is associated with fewer organ failure-free days in pediatric severe sepsis.

Methods:

Four hundred one children were enrolled in the parent study. Children were excluded from these analyses if they received extracorporeal membrane oxygenation (n = 22) or died (n = 1) before sepsis day 2. Propensity-adjusted analyses compared children who received RBC transfusion on or before sepsis day 2 (early RBC transfusion) with those who did not. Logistic regression was used to model the propensity to receive early RBC transfusion. A weighted cohort was constructed using stabilized inverse probability of treatment weights. Variables in the weighted cohort with absolute standardized differences >0.15 were added to final multivariable models.

Results:

Fifty percent of children received at least one RBC transfusion. The majority (68%) of first transfusions were on or before sepsis day 2. Early RBC transfusion was not independently associated with organ failure-free (−0.34 [95%CI: −2, 1.3] days) or PICU-free days (−0.63 [−2.3, 1.1]), but was associated with the secondary outcome of higher mortality (aOR 2.9 [1.1, 7.9]).

Conclusions:

RBC transfusion is common in pediatric severe sepsis and may be associated with adverse outcomes. Future studies are needed to clarify these associations, to understand patient-specific transfusion risks, and to develop more precise transfusion strategies.
Time trends in social contacts before and during the COVID-19 pandemic: the CONNECT study
Authors: Drolet Mélanie , Godbout Aurélie , Mondor Myrto , Béraud Guillaume , Drolet-Roy Léa , Lemieux-Mellouki Philippe , Bureau Alexandre , Demers Éric , Boily Marie-Claude , Sauvageau Chantal , De Serres Gaston , Hens Niel , Beutels Philippe , Dervaux Benoit , Brisson Marc
Published: October 2021

Background

Since the beginning of the COVID-19 pandemic, many countries, including Canada, have adopted unprecedented physical distancing measures such as closure of schools and non-essential businesses, and restrictions on gatherings and household visits. We described time trends in social contacts for the pre-pandemic and pandemic periods in Quebec, Canada.

Methods

CONNECT is a population-based study of social contacts conducted shortly before (2018/2019) and during the COVID-19 pandemic (April 2020 – February 2021), using the same methodology for both periods. We recruited participants by random-digit-dialing and collected data by self-administered web-based questionnaires. Questionnaires documented socio-demographic characteristics and social contacts for two assigned days. A contact was defined as a two-way conversation at a distance ≤2 meters or as a physical contact, irrespective of masking. We used weighted generalized linear models with a Poisson distribution and robust variance (taking possible overdispersion into account) to compare the mean number of social contacts over time by characteristics.

Results

A total of 1291 and 5516 Quebecers completed the study before and during the pandemic, respectively. Contacts significantly decreased from a mean of 8 contacts/day prior to the pandemic to 3 contacts/day during the spring 2020 lockdown. Contacts remained lower than the pre-COVID period thereafter (lowest=3 contacts/day during the Christmas 2020/2021 holidays, highest=5 in September 2020). Contacts at work, during leisure activities/other locations, and at home with visitors showed the greatest decreases since the beginning of the pandemic. All sociodemographic subgroups showed significant decreases of contacts since the beginning of the pandemic. The mixing matrices illustrated the impact of public health measures (e.g. school closure, gathering restrictions) with fewer contacts between children/teenagers and fewer contacts outside of the three main diagonals of contacts between same-age partners/siblings and between children and their parents.

Conclusion

Physical distancing measures in Quebec significantly decreased social contacts, which most likely mitigated the spread of COVID-19.
Sunk cost sensitivity in mice, rats, and humans on the Restaurant Row and WebSurf tasks cannot be explained by attrition biases alone
Authors: Redish A. David , Sweis Brian M. , Abram Samantha , Duin Anneke , Kazinka Rebecca , Kocharian Adrina , MacDonald Angus , Schmidt Brandy , Schmitzer-Tobert Neil , Thomas Mark
Published: October 2021

In a recent bioRxiv preprint, Ott et al. argue that sensitivities to sunk costs that have been reported in two serial foraging tasks (the Restaurant Row task in mice and rats, and the Web-Surf task in humans) may be due to simple consequences of the way that subjects perform these tasks and not due to an actual sensitivity to sunk costs. However, several variants of these tasks have been studied, in which the sensitivity to sunk costs changes. In order to test the Ott et al. model against these experimental observations, we simulated the model under these additional experimental conditions. We find that it is incompatible with the actual data. While we applaud the simplicity of the Ott et al. model, we must reject it as an explanation for the observed sensitivity to sunk costs seen in these tasks. We thus conclude that the alternative explanation - that mice, rats, and humans are sensitive to actual sunk costs in these tasks - is a better explanation for the data.
Coevolution of interacting proteins through non-contacting and non-specific mutations
Authors: Ding David , Green Anna G. , Wang Boyuan , Vo Lite Thuy-Lan , Weinstein Eli N. , Marks Debora S. , Laub Michael T.
Published: October 2021

Proteins often accumulate neutral mutations that do not affect current functions1but can profoundly influence future mutational possibilities and functions2–4. Understanding such hidden potential has major implications for protein design and evolutionary forecasting5–7, but has been limited by a lack of systematic efforts to identify potentiating mutations8,9. Here, through the comprehensive analysis of a bacterial toxin-antitoxin system, we identified all possible single substitutions in the toxin that enable it to tolerate otherwise interface-disrupting mutations in its antitoxin. Strikingly, the majority of enabling mutations in the toxin do not contact, and promote tolerance non-specifically to, many different antitoxin mutations, despite covariation in homologs occurring primarily between specific pairs of contacting residues across the interface. In addition, the enabling mutations we identified expand future mutational paths that both maintain old toxin-antitoxin interactions and form new ones. These non-specific mutations are missed by widely used covariation and machine learning methods10,11. Identifying such enabling mutations will be critical for ensuring continued binding of therapeutically relevant proteins, such as antibodies, aimed at evolving targets12–14.
Vagus nerve stimulation increases stomach-brain coupling via a vagal afferent pathway
Authors: Müller Sophie , Teckentrup Vanessa , Rebollo Ignacio , Hallschmid Manfred , Kroemer Nils B.
Published: October 2021

Maintaining energy homeostasis is vital and supported by vagal signaling between digestive organs and the brain. Previous research has established a gastric network in the brain that is phase synchronized with the rhythm of the stomach, but tools to perturb its function were lacking. Here, we investigated the effect of acute right-sided transcutaneous auricular vagus nerve stimulation (taVNS) versus sham stimulation (randomized crossover-design) on stomach-brain coupling. In line with preclinical research, taVNS increased stomach-brain coupling in the nucleus of the solitary tract (NTS) and the midbrain while boosting coupling across the brain. Crucially, in the cortex, taVNS-induced changes in coupling occurred primarily in transmodal regions and were associated with changes in hunger ratings as indicators of the subjective metabolic state. Hence, taVNS alters stomach-brain coupling via an NTS-midbrain pathway that signals gut-induced reward, potentially paving the way for novel treatments in disorders such as Parkinson’s disease or depression.

Graphical Abstract

Highlights

Transcutaneous vagus nerve stimulation (taVNS) can emulate interoceptive signals

taVNS boosts stomach-brain coupling in the brainstem, midbrain, and transmodal cortex

taVNS-induced changes in stomach-brain coupling mirror subjective hunger ratings
A partial reduction of Drp1 enhances mitophagy, autophagy, mitochondrial biogenesis, dendritic spines and synaptic activity in a transgenic Tau mouse model of Alzheimer disease
Authors: Kandimalla Ramesh , Manczak Maria , Pradeepkiran Jangampalli Adi , Reddy P. Hemachandra
Published: October 2021

The purpose of our study is to understand the impact of a partial dynamin-related protein 1 (Drp1) on cognitive behavior, mitophagy/autophagy, mitochondrial and synaptic activities in transgenic Tau mice in Alzheimer’s disease (AD). Our lab reported increased levels of Aβ and P-Tau, and abnormal interactions between Aβ and Drp1, P-Tau and Drp1 induced increased mitochondrial fragmentation and reduced fusion and synaptic activities in AD. These abnormal interactions, result in the proliferation of dysfunctional mitochondria in AD neurons. Recent research on mitochondria revealed that fission protein Drp1 is largely implicated in mitochondrial dynamics in AD. To determine the impact of reduced Drp1 in AD, we recently crossed transgenic Tau mice with Drp1 heterozygote knockout (Drp1+/-) mice and generated double mutant (Drp1+/- X Tau) mice. In the current study, we assessed cognitive behavior, mRNA and protein levels of mitophagy, autophagy, mitochondrial biogenesis, dynamics and synaptic genes, mitochondrial morphology & mitochondrial function, dendritic spines in Tau mice relative to double mutant mice. When compared to Tau mice, double mutant mice did better on Morris Maze (reduced latency to find hidden platform, increased swimming speed and time spent on quadrant) and rotarod (stayed a longer period of time) tests. Both mRNA and proteins levels autophagy, mitophagy, mitochondrial biogenesis and synaptic proteins were increased in double mutant mice compared to Tau mice. Dendritic spines were significantly increased; mitochondrial number is reduced and length is increased in double mutant mice. Based on these observations, we conclude that reduced Drp1 is beneficial in a symptomatic-transgenic Tau mice.
Impact of stimulation location relative to grey and white matter on single pulse electrical stimulation responses in the human brain
Authors: Paulk Angelique C. , Zelmann Rina , Crocker Britni , Widge Alik S. , Dougherty Darin D. , Eskandar Emad N. , Weisholtz Daniel S. , Richardson R. Mark , Cosgrove G. Rees , Williams Ziv M. , Cash Sydney S.
Published: October 2021

Background

Electrical neuromodulation is an increasingly common therapy for a wide variety of neuropsychiatric diseases. Unfortunately, therapeutic efficacy is inconsistent, possibly a result of our limited understanding of the mechanisms and the massive stimulation parameter space.

Objective/Hypothesis

To better understand the role different parameters play in inducing a response, we systematically examined single pulse-induced cortico-cortico evoked potentials (CCEP) as a function of stimulation amplitude, duration and location in the brain and relative to grey and white matter.

Methods

We measured voltage peak amplitudes and area under the curve of intracranially recorded stimulation responses as a function of distance from the stimulation site, pulse width, current injected, location relative to grey and white matter, and brain region stimulated (N=52, n=719 stimulation sites).

Results

Increasing stimulation pulse width increased response values near the stimulation location. Increasing stimulation amplitude (current) increased responses nonlinearly. Locally (<15 mm from the stimulation site), stimulation closer to the grey matter-white matter boundary induced larger responses. In contrast, for distant sites (>15 mm), white matter stimulation consistently produced larger responses than stimulation in or near grey matter. These relationships were different between cingulate, lateral prefrontal, and lateral temporal cortical stimulation.

Conclusion

These results demonstrate the importance of location and stimulation parameters in inducing a specific output and indicate that a stronger local response may require stimulation in the grey-white boundary while stimulation in the white matter may be needed for network activation, suggesting that stimulation location can be tailored for a specific outcome, key to informed neuromodulatory therapy.

Highlights

Intracranial single pulse electrical stimulation (SPES) response increases with increased pulse duration mostly near the stimulation site

SPES response varies nonlinearly with injected current with an effect of distance from the stimulation site.

SPES near the grey-white boundary and 90° to the nearest cortical axis induces larger local responses, but white matter stimulation produces larger distant responses.

The relationship between SPES location and responses depends on brain region stimulated
Global port survey quantifies commercial shipping’s effect on biodiversity
Authors: Andrés Jose , Czechowski Paul , Grey Erin , Saebi Mandana , Andres Kara , Brown Christopher , Chawla Nitesh , Corbett James J. , Brys Rein , Cassey Phillip , Correa Nancy , Deveney Marty R. , Egan Scott P. , Fisher Joshua P. , vanden Hooff Rian , Knapp Charles R. , Leong Sandric Chee Yew , Neilson Brian J. , Paolucci Esteban M. , Pfrender Michael E. , Pochardt Meredith R. , Prowse Thomas A.A. , Rumrill Steven S. , Scianni Chris , Sylvester Francisco , Tamburri Mario N. , Therriault Thomas W. , Yeo Darren C.J. , Lodge David
Published: October 2021

Spread of nonindigenous organisms by shipping is one of the largest threats to coastal ecosystems. Limited monitoring and understanding of this phenomenon currently hinder development of effective prevention policies. Surveying ports in North America, South America, Europe, Southeast Asia, and Australia we explored environmental DNA community profiles evident of ship-born species spread. We found that community similarities between ports increased with the number of ship voyages, particularly if the ports had similar environments, and when indirect stepping-stone connections were considered. We also found 57 known non-indigenous taxa, some in hitherto unreported locations. We demonstrate the usefulness of eDNA-based tools for global biodiversity surveys, and highlight that shipping homogenizes biodiversity in predictable that could inform policy and management.