bluuebunny/crossref_metadata_2025 huggingface dataset:
A survey of reported changes in diet and activity with the FreeStyle Libre flash glucose monitor: a pilot study
Authors: Arnason Terra , Cameron Amanda , Nour Munier , Inman Mark , Mansell Kerry
Published: February 2022

Introduction: Flash glucose monitors (FGMs) are increasingly popular with people with diabetes. We aimed to see if the use of the FreeStyle Libre affected users’ behaviours regarding dietary choices and exercise.

Methods: An online questionnaire was developed using Voxco Survey Platform 2018 and was completed between 18 May and 14 August 2018. The questionnaire consisted of yes/no and 6‐point Likert scale questions to assess the effects of FGM on diet and exercise patterns. Anyone with diabetes who had been using the FGM for at least four weeks prior to study commencement was eligible to participate.

Results: Forty‐one participants completed the questionnaire; the majority were < 18 years old (29/41; 70.7%), and had type 1 diabetes (37/41; 90.2%). As a result of using the FGM, 58.6% (17/29) of paediatric participants indicated they noticed specific foods affected their blood glucose levels that they were not previously aware of, and 31.0% (9/29) indicated that they changed their carbohydrate choices to lower glycaemic index foods. In all, 72.4% (21/29) of paediatric participants indicated that they felt more confident in participating in exercise, 20.7% (6/29) indicated that they initiated new exercise, and 13.8% (4/29) indicated that they increased their amount of exercise as a result of using the FGM.

Conclusions: In this study of primarily paediatric patients, some participants reported improved confidence to participate in exercise, as well as making positive dietary changes as a result of using the FGM. Further study is required to confirm if the FGM may have positive and sustained effects on these parameters. Copyright © 2022 John Wiley & Sons.
Patient risk factors for opioid‐related adverse drug events in hospitalized patients: A systematic review
Authors: Yiu Chin Hang , Vitharana Nilru , Gnjidic Danijela , Patanwala Asad E. , Fong Ian , Rimington Joanne , Begley David , Bugeja Bernadette , Penm Jonathan
Published: February 2022

Introduction

Opioid utilization has increased fourfold over the past two decades among developed countries. Previous studies have found that opioid‐related adverse drug events (ORADEs) are strongly associated with adverse clinical outcomes in hospitalized patients. The Society of Hospital Medicine in the United States recently published a Consensus Statement regarding opioid safety and suggested that extra caution is needed when using opioids in patients with risk factors for ORADEs. This systematic review aimed to summarize common patient risk factors for ORADEs in hospitalized patients.

Methods

Five databases were searched including Medline, Embase, Cochrane Central Register of Controlled Trials, International Pharmaceutical Abstracts, and Scopus. Search themes include opioids, adverse drug events, and acute care settings. Original full‐text studies that were published and identified patient risk factors for ORADEs in hospitalized patients were included.

Results

A total of 16 observational studies were included, with only two studies considered as poor quality. Seven studies focused on severe ORADEs including over‐sedation and respiratory depression. Common patient risk factors for severe ORADEs included comorbidities (eg, sleep apnea and renal diseases), concurrent use of sedatives, and prior opioid exposure. Nine studies focused on a combination of general ORADEs and common patient risk factors included advanced age, male gender, comorbidities (eg, chronic obstructive pulmonary disease and neurologic disorders), concurrent use of sedating medications, and prior opioid exposure.

Conclusions

Successful identification of patient risk factors for ORADEs summarized by this systematic review could benefit clinicians when deciding on the appropriateness of opioid therapy in hospital patients. Future studies could focus on developing a validated risk assessment tool based on these risk factors.
Using professional development workshops to support school professionals' capacities to promote students' social, emotional, and behavioral health
Authors: Kaye Amy J. , Pejic Vanja , Moffa Kathryn , Jordan Molly , Dennery Kristine M. , DeMaso David R.
Published: February 2022

The objective of this study was to evaluate an innovative model for providing high quality professional development workshops (PDWs) in the context of a Learning Collaborative (LC) based intervention to build the capacities of school professionals to promote the social, emotional, and behavioral health of students. Eleven PDWs totaling 27.5 h were facilitated with 10 school‐based teams. Matched pre‐ and post‐surveys were completed by a total of 177 participants across the 10 teams. Results demonstrate significant increases in participants' self‐reported knowledge, skills, and self‐efficacy from pre‐ to post‐participation in each workshop, as well as high ratings of overall satisfaction. LC‐based PDWs, facilitated by school‐based behavioral health (BH) providers, hold promise for enhancing school professionals' capacities to address the critical social, emotional, and behavioral health needs of their students. Implications for administrators, school‐based BH providers, partnering community‐based agencies, and policymakers in sustainably replicating this promising, data‐driven model in schools are discussed.
The success of the Cystic Fibrosis Registry of Turkey for improvement of patient care
Authors: Asfuroglu Pelin , Sismanlar Eyuboglu Tugba , Aslan Ayse Tana , Gursoy Tugba Ramasli , Emiralioglu Nagehan , Yalcin Ebru , Kiper Nural , Sen Velat , Sen Hadice Selimoglu , Altintas Derya Ufuk , Ozcan Dilek , Kilinc Ayse Ayzit , Cokugras Haluk , Baskan Azer Kilic , Yazan Hakan , Erenberk Ufuk , Dogan Guzide , Unal Gokcen , Yilmaz Asli Imran , Keskin Ozlem , Arik Elif , Kucukosmanoglu Ercan , Irmak Ilim , Damadoglu Ebru , Ozturk Gokcen Kartal , Gulen Figen , Basaran Abdurrahman Erdem , Bingol Aysen , Cekic Sukru , Sapan Nihat , Kilic Gonca , Harmanci Koray , Kose Mehmet , Ozdemir Ali , Tugcu Gokcen Dilsa , Polat Sanem Eryilmaz , Hangul Melih , Ozcan Gizem , Aydin Zeynep Gokce Gayretli , Yuksel Hasan , Topal Erdem , Ozdogan Sebnem , Caltepe Gonul , Suleyman Ayse , Can Demet , Ekren Pervin Korkmaz , Bal Cem Murat , Kilic Mehmet , Cinel Guzin , Cobanoglu Nazan , Pekcan Sevgi , Cakir Erkan , Ozcelik Ugur , Dogru Deniz
Published: February 2022

Background

Cystic fibrosis (CF) registries play an essential role in improving disease outcomes of people with CF. This study aimed to evaluate the association of newly established CF registry system in Turkey on follow‐up, clinical, growth, treatment, and complications of people with this disease.

Methods

Age at diagnosis, current age, sex, z‐scores of weight, height and body mass index (BMI), neonatal screening results, pulmonary function tests, history of meconium ileus, medications, presence of microorganisms, and follow‐up were evaluated and compared to data of people with CF represented in both 2017 and 2019 registry data.

Results

There were 1170 people with CF in 2017 and 1637 in 2019 CF registry. Eight hundred and fourteen people were registered in both 2017 and 2019 of whom z‐scores of heights and BMI were significantly higher in 2019 (p = 0.002, p =0.039, respectively). Inhaled hypertonic saline, bronchodilator, and azithromycin usages were significantly higher in 2019 (p =0.001, p = 0.001, p = 0.003, respectively). The percent predicted of forced expiratory volume in  1 sec and forced vital capacity were similar in 2017 and 2019 (88% and 89.5%, p = 0.248 and 84.5% and 87%, p =0.332, respectively). Liver diseases and osteoporosis were significantly higher, and pseudo‐Bartter syndrome (PBS) was significantly lower in 2019 (p = 0.011, p = 0.001, p = 0.001, respectively).

Conclusions

The z‐scores of height and BMI were higher, the use of medications that protect and improve lung functions was higher and incidence of PBS was lower in 2019. It was predicted that registry system increased the care of people with CF regarding their follow‐up. The widespread use of national CF registry system across the country may be beneficial for the follow‐up of people with CF.
Safety management and safety outcomes in oil and gas industry in Malaysia: Safety compliance as a mediator
Authors: Ajmal Muhammad , Isha Ahmad Shahrul Nizam , Nordin Shahrina Md , Rasheed Saba , Al‐Mekhlafi Al‐Baraa Abdulrahman , Naji Gehad Mohammad Ahmad
Published: February 2022

The purpose of this study was to know the mediating role of safety compliance between safety management and safety outcomes in Malaysia's oil and gas industry. The cross‐sectional survey utilized a quantitative method for survey design. The data were collected through the convenience sampling technique via email from operation and production departments employees of the downstream sector. The analysis of 280 responses proved that safety compliance plays a significant role in enhancing safety outcomes and reducing occupational accidents and occupational injuries. Therefore, this study is helpful for practitioners to understand the importance of safety compliance and also safety management indicators in safety‐sensitive organizations, for example, the oil and gas industry of Malaysia. Furthermore, by filling the existing research gap, this study also provides fertile ground for future research and broad implications for the research industry.
Psychopharmacology research: Pandemic reverberations
Authors: Price Lawrence H.
Published: February 2022

As I perused the contents of this month's Update, three studies in particular struck me as calling out for comment. Two of them are worth noting because they are timely and, well, attention‐getting. The third is more conventionally notable, although as I thought about it, I realized it resonated in an unexpected way with the other two.
Grignard Reagents as Niche Bases in the Synthesis of Pharmaceutically Relevant Molecules
Authors: Samineni Ramesh , Eda Vishnuvardhana , Rao Pallavi , Sen Saikat , Oruganti Srinivas
Published: February 2022

Grignard reagents are routinely employed in the pharmaceutical industry as reliablesynthetic equivaents of carbanion synthons for construction of new C−C bonds. The present review however does not focuson these well documented applications of Grignard reagents as carbon nucleophiles. Rather, it documents certain unique case studies wherein, despite the material loss entailed as R−H, a Grignard reagent (RMgX) was strategically deployed as a Bronsted base to abstract an active hydrogen and effect a desired transformation in the synthesis of APIs and pharmaceutically relevant natural products.
Advances in Graphene/Inorganic Nanoparticle Composites for Catalytic Applications
Authors: Adil Syed Farooq , Ashraf Muhammad , Khan Mujeeb , Assal Mohamed E. , Shaik Mohammed Rafi , Kuniyil Mufsir , Al‐Warthan Abdulrahman , Siddiqui Mohammed Rafiq H. , Tremel Wolfgang , Tahir Muhammad Nawaz
Published: February 2022

Graphene‐based nanocomposites with inorganic (metal and metal oxide) nanoparticles leads to materials with high catalytic activity for a variety of chemical transformations. Graphene and its derivatives such as graphene oxide, highly reduced graphene oxide, or nitrogen‐doped graphene are excellent support materials due to their high surface area, their extended π‐system, and variable functionalities for effective chemical interactions to fabricate nanocomposites. The ability to fine‐tune the surface composition for desired functionalities enhances the versatility of graphene‐based nanocomposites in catalysis. This review summarizes the preparation of graphene/inorganic NPs based nanocomposites and their use in catalytic applications. We discuss the large‐scale synthesis of graphene‐based nanomaterials. We have also highlighted the interfacial electronic communication between graphene/inorganic nanoparticles and other factors resulting in increased catalytic efficiencies.
Nanoflowers: A New Approach of Enzyme Immobilization
Authors: da Costa Felipe Pereira , Cipolatti Eliane Pereira , Furigo Junior Agenor , Oliveira Henriques Rosana
Published: February 2022

Enzymes are biocatalysts known for versatility, selectivity, and brand operating conditions compared to chemical catalysts. However, there are limitations to their large‐scale application, such as the high costs of enzymes and their low stability under extreme reaction conditions. Immobilization techniques can efficiently solve these problems; nevertheless, most current methods lead to a significant loss of enzymatic activity and require several steps of activation and functionalization of the supports. In this context, a new form of immobilization has been studied: forming organic‐inorganic hybrids between metal phosphates as inorganic parts and enzymes as organic parts. Compared to traditional immobilization methods, the advantages of these nanomaterials are high surface area, simplicity of synthesis, high stability, and catalytic activity. The current study presents an overview of organic‐inorganic hybrid nanoflowers and their applications in enzymatic catalysis.
Renewable Electricity Enables Green Routes to Fine Chemicals and Pharmaceuticals
Authors: Murtaza Ayesha , Qamar Muhammad Awais , Saleem Kaynat , Hardwick Tomas , Zia ul haq  , Shirinfar Bahareh , Ahmed Nisar
Published: February 2022

Syntheses of chemicals using renewable electricity and when generating high atom economies are considered green and sustainable processes. In the present state of affairs, electrochemical manufacturing of fine chemicals and pharmaceuticals is not as common place as it could be and therefore, merits more attention. There is also a need to turn attention toward the electrochemical synthesis of valuable chemicals from recyclable greenhouse gases that can accelerate the process of circular economy. CO2 emissions are the major contributor to human‐induced global warming. CO2 conversion into chemicals is a valuable application of its utilisation and will contribute to circular economy while maintaining environmental sustainability. Herein, we present an overview of electro‐carboxylation, including mechanistic aspects, which forms carboxylic acids using molecular carbon dioxide. We also discuss atom economies of electrochemical fluorination, methoxylation and amide formation reactions.
Recent Developments in the Removal of Dyes from Water by Starch‐Based Adsorbents
Authors: Ihsanullah Ihsanullah , Bilal Muhammad , Jamal Arshad
Published: February 2022

Starch‐based adsorbents have demonstrated excellent potential for the removal of various noxious dyes from wastewater. This review critically evaluates the recent progress in applications of starch‐based adsorbents for the removal of dyes from water. The synthesis methods of starch‐based composites and their effects on physicochemical characteristics of produced adsorbents are discussed. The removal of various dyes by starch‐based adsorbents are described in detail, with emphasis on the effect of key parameters, adsorption mechanism and their reusability potential. The key challenges related to the synthesis and applications of starch‐based adsorbents in water purification are highlighted. Based on the research gaps, recommendations for future research are made. The evaluation of starch‐based adsorbents would contribute to the development of sustainable water treatment options in near future.
Response of stream ecosystem structure to heavy metal pollution: context-dependency of top-down control by fish
Authors: Rubio-Gracia Francesc , Argudo María , Zamora Lluís , Clements William H. , Vila-Gispert Anna , Casals Frederic , Guasch Helena
Published: February 2022

The stress-gradient hypothesis predicts that biotic interactions within food webs are context dependent, since environmental stressors can attenuate consumer–prey interactions. Yet, how heavy metal pollution influences the impacts of predatory fish on ecosystem structure is unknown. This study was conducted in the Osor stream (Spain), which features a metal (mainly Zn) pollution gradient. We aimed to determine how the responses of benthic communities to the presence and absence of predatory fish interact with environmental stress and to test whether the top-down control of top predators is context dependent. To address these questions, periphyton biomass and macroinvertebrate densities were determined throughout an exclosure/enclosure mesocosm experiment using the Mediterranean barbel (Barbus meridionalis) as a top predator. The monitoring study showed that metal accumulation in periphyton and macroinvertebrates reflected patterns observed in water. The mesocosm study showed that fish predation effects on larval chironomids were not context-dependent and that periphyton biomass was markedly lower in the presence of fish regardless of metal pollution levels. This strong top-down control on periphytic algae was attributed to the foraging behaviour of fish causing bioturbation. In contrast, the top predator removal revealed grazer-periphyton interactions, which were mediated by heavy metal pollution. That is, periphyton benefitted from a lower grazing pressure in the metal-polluted sites. Together, our results suggest that the top–down control by fishes depends more on functional traits (e.g. feeding behaviour) than on feeding guild, and demonstrate the capacity of top predators to modify anthropogenic stressor effects on stream food-web structure.
Postpartum urinary incontinence and birth outcomes as a result of the pushing technique: a systematic review and meta-analysis
Authors: Shinozaki Katsuko , Suto Maiko , Ota Erika , Eto Hiromi , Horiuchi Shigeko
Published: February 2022

Introduction and hypothesis

Directed pushing while using the Valsalva maneuver is shown to lead to bladder neck descent, especially in women with urinary incontinence (UI). There is insufficient evidence about the benefits or adverse effects between the pushing technique during the second stage of labor and urinary incontinence postpartum. The objective of this study was to evaluate the effects of the pushing technique for women during labor on postpartum UI and birth outcomes.

Methods

Scientific databases were searched for studies relating to postpartum urinary incontinence and birth outcomes when the pushing technique was used from 1986 until 2020. RCTs that assessed healthy primiparas who used the pushing technique in the second stage of labor were included. In accordance with Cochrane Handbook guidelines, risk of bias was assessed and meta-analyzed. Certainty of evidence was assessed using the GRADE approach.

Results

Seventeen RCTs (4606 primiparas) were included. The change in UI scores from baseline to postpartum was significantly lower as a result of spontaneous pushing (two studies; 867 primiparas; standardized mean difference: SMD –0.18, 95% CI –0.31 to –0.04). Although women were in the recumbent position during the second stage, directed pushing group showed a significantly shorter labor by 21.39 min compared with the spontaneous pushing group: there was no significant difference in the duration of the second stage of labor between groups.

Conclusions

Primiparas who were in the upright position and who experienced spontaneous pushing during the second stage of labor could reduce their UI score from baseline to postpartum.
A framework for chemical safety assessment incorporating new approach methodologies within REACH
Authors: Ball Nicholas , Bars Remi , Botham Philip A. , Cuciureanu Andreea , Cronin Mark T. D. , Doe John E. , Dudzina Tatsiana , Gant Timothy W. , Leist Marcel , van Ravenzwaay Bennard
Published: February 2022

The long-term investment in new approach methodologies (NAMs) within the EU and other parts of the world is beginning to result in an emerging consensus of how to use information from in silico, in vitro and targeted in vivo sources to assess the safety of chemicals. However, this methodology is being adopted very slowly for regulatory purposes. Here, we have developed a framework incorporating in silico, in vitro and in vivo methods designed to meet the requirements of REACH in which both hazard and exposure can be assessed using a tiered approach. The outputs from each tier are classification categories, safe doses, and risk assessments, and progress through the tiers depends on the output from previous tiers. We have exemplified the use of the framework with three examples. The outputs were the same or more conservative than parallel assessments based on conventional studies. The framework allows a transparent and phased introduction of NAMs in chemical safety assessment and enables science-based safety decisions which provide the same level of public health protection using fewer animals, taking less time, and using less financial and expert resource. Furthermore, it would also allow new methods to be incorporated as they develop through continuous selective evolution rather than periodic revolution.
Discriminants and Semi-orthogonal Decompositions
Authors: Kite Alex , Segal Ed
Published: February 2022

The derived categories of toric varieties admit semi-orthogonal decompositions coming from wall-crossing in GIT. We prove that these decompositions satisfy a Jordan–Hölder property: the subcategories that appear, and their multiplicities, are independent of the choices made. For Calabi–Yau toric varieties wall-crossing instead gives derived equivalences and autoequivalences, and mirror symmetry relates these to monodromy around the GKZ discriminant locus. We formulate a conjecture equating intersection multiplicities in the discriminant with the multiplicities appearing in certain semi-orthogonal decompositions. We then prove this conjecture in some cases.
The “hyperdense basivertebral vein” sign: another marker of a CSF-venous fistula
Authors: Lützen Niklas , Kremers Nico , Fung Christian , Beck Jürgen , Urbach Horst
Published: February 2022

CSF-venous fistulas — initially described in 2014 — are a significant cause of spontaneous intracranial hypotension. Dynamic lateral decubitus digital subtraction and/or CT myelography typically show a hyperdense paraspinal vein. In case of a central drainage toward the internal vertebral venous plexus, it is the “hyperdense basivertebral vein” which should be searched for carefully.
Factors affecting the isolation and diversity of marine sponge-associated bacteria
Authors: Anteneh Yitayal S. , Yang Qi , Brown Melissa H. , Franco Christopher M. M.
Published: February 2022

Marine sponges are an ideal source for isolating as yet undiscovered microorganisms with some sponges having about 50% of their biomass composed of microbial symbionts. This study used a variety of approaches to investigate the culturable diversity of the sponge-associated bacterial community from samples collected from the South Australian marine environment. Twelve sponge samples were selected from two sites and their bacterial population cultivated using seven different agar media at two temperatures and three oxygen levels over 3 months. These isolates were identified using microscopic, macroscopic, and 16S rRNA gene analysis. A total of 1234 bacterial colonies were isolated which consisted of four phyla: Actinobacteria, Firmicutes, Proteobacteria, and Bacteroidetes, containing 21 genera. The diversity of the bacterial population was demonstrated to be influenced by the type of isolation medium, length of the incubation period and temperature, sponge type, and oxygen level. The findings of this study showed that marine sponges of South Australia can yield considerable bacterial culturable diversity if a comprehensive isolation strategy is implemented. Two sponges, with the highest and the lowest diversity of culturable isolates, were examined using next-generation sequencing to better profile the bacterial population. A marked difference in terms of phyla and genera was observed using culture-based and culture-independent approaches. This observed variation displays the importance of utilizing both methods to reflect a more complete picture of the microbial population of marine sponges.

Key points

Improved bacterial diversity due to long incubations, 2 temperatures, and 3 oxygen levels.

Isolates identified by morphology, restriction digests, and 16S rRNA gene sequencing.

At least 70% of culturable genera were not revealed by NGS methods.
Succeeding in Continuing Trauma Education During a Pandemic
Authors: Mitchnik Ilan Y. , Rivkind Avraham I.
Published: February 2022

Background

Corona virus disease 2019 (Covid‐19) impacted continuing medical education programs such as the Advanced Trauma Life Support (ATLS) course. Modifications made to medical training like teleconferencing could affect students’ learning success. We sought to evaluate the effects of the American College of Surgeons modifications on success rates in passing the ATLS course.

Methods

This study evaluated 28 ATLS 10th edition courses educating 898 students at our region before and after Covid‐19 modifications. Traditional two‐day courses were performed in‐person while modified courses were conducted with a one‐day teleconference followed by a second in‐person practical day. We compared the characteristics and course pass rates between the traditional and modified ATLS courses.

Results

Modified ATLS courses had significantly lower pass rates (81.0%; 95% confidence interval = [74.8–87.3]) compared to traditional ATLS courses (94.3%; [92.2–96.3]).

Conclusions

Modifications to the ATLS course are associated with lower student pass. This is possibly due to ineffective knowledge consolidation. Better modifications to the course are required such as use of electronic learning tools with modification to course schedule or returning to the traditional course but with the use of Covid‐19 vaccines and other protective measures. These suggestions should be considered and evaluated further by ATLS program leaders.
Monitoring multiple myeloma in the peripheral blood based on cell-free DNA and circulating plasma cells
Authors: Mack Elisabeth K. M. , Hartmann Sören , Ross Petra , Wollmer Ellen , Mann Christoph , Neubauer Andreas , Brendel Cornelia , Hoffmann Jörg
Published: February 2022

With the advent of novel, highly effective therapies for multiple myeloma (MM), classical serologic monitoring appears insufficient for response assessment and prediction of relapse. Moreover, serologic studies in MM are hampered by interference of therapeutic antibodies. The detection of malignant plasma cell clones by next generation sequencing (NGS) or multiparameter flow cytometry (MFC) circumvents these difficulties and can be performed in the peripheral blood (pB) by targeting circulating cell-free DNA (cfDNA) or circulating plasma cells (CPCs), thus also avoiding an invasive sampling procedure. Here, we applied NGS of VJ light chain (LC) rearrangements in cfDNA and MFC of magnetically-enriched CD138-positive CPCs (me-MFC) to investigate disease burden in unselected MM patients. Sequencing was successful for 114/130 (87.7%) cfDNA samples and me-MFC results were analyzable for 196/205 (95.6%) samples. MM clones were detectable in 38.9% of samples taken at initial diagnosis or relapse (ID/RD), but only in 11.8% of samples taken during complete remission (CR). Circulating MM plasma cells were present in 83.3% of ID/RD samples and 9.9% of CR samples. Residual disease assessment by NGS or me-MFC in samples taken during very good partial remission or CR was 80% concordant. Notably, 4/4 (NGS) and 5/8 (me-MFC) positive CR samples were from patients with oligo- or non-secretory myeloma. The time to progression was shorter if there was evidence of residual myeloma in the pB. Together, our findings indicate that our two novel analytical approaches accurately indicate the course of MM and may be particularly valuable for monitoring patients with serologically non-trackable disease.
Reverse re-modelling chronic heart failure by reinstating heart rate variability
Authors: Shanks J. , Abukar Y. , Lever N. A. , Pachen M. , LeGrice I. J. , Crossman D. J. , Nogaret A. , Paton J. F. R. , Ramchandra R.
Published: February 2022

Heart rate variability (HRV) is a crucial indicator of cardiovascular health. Low HRV is correlated with disease severity and mortality in heart failure. Heart rate increases and decreases with each breath in normal physiology termed respiratory sinus arrhythmia (RSA). RSA is highly evolutionarily conserved, most prominent in the young and athletic and is lost in cardiovascular disease. Despite this, current pacemakers either pace the heart in a metronomic fashion or sense activity in the sinus node. If RSA has been lost in cardiovascular disease current pacemakers cannot restore it. We hypothesized that restoration of RSA in heart failure would improve cardiac function. Restoration of RSA in heart failure was assessed in an ovine model of heart failure with reduced ejection fraction. Conscious 24 h recordings were made from three groups, RSA paced (n = 6), monotonically paced (n = 6) and heart failure time control (n = 5). Real-time blood pressure, cardiac output, heart rate and diaphragmatic EMG were recorded in all animals. Respiratory modulated pacing was generated by a proprietary device (Ceryx Medical) to pace the heart with real-time respiratory modulation. RSA pacing substantially increased cardiac output by 1.4 L/min (20%) compared to contemporary (monotonic) pacing. This increase in cardiac output led to a significant decrease in apnoeas associated with heart failure, reversed cardiomyocyte hypertrophy, and restored the T-tubule structure that is essential for force generation. Re-instating RSA in heart failure improves cardiac function through mechanisms of reverse re-modelling; the improvement observed is far greater than that seen with current contemporary therapies. These findings support the concept of re-instating RSA as a regime for patients who require a pacemaker.
Changing trends in the microvascular reconstruction and oral rehabilitation following maxillary cancer
Authors: Rogers Simon N. , Adatia Ashni , Hackett Stephanie , Boscarino Angela , Patel Anika , Lowe Derek , Butterworth Christopher J.
Published: February 2022

Purpose

The maxillectomy defect is complex and the best means to achieve optimal reconstruction, and dental rehabilitation is a source of debate. The refinements in zygomatic implant techniques have altered the means and speed by which rehabilitation can be achieved and has also influenced the choice regarding ideal flap reconstruction. The aim of this study is to report on how the method of reconstruction and oral rehabilitation of the maxilla has changed since 1994 in our Institution, and to reflect on case mix and survival.

Methods

Consecutive head and neck oncology cases involving maxillary resections over a 27-year period between January 1994 and November 2020 were identified from hospital records and previous studies. Case note review focussed on clinical characteristics, reconstruction, prosthetic rehabilitation, and survival.

Results

There were 186 patients and the tumour sites were: alveolus for 56% (104), hard palate for 19% (35), maxillary sinus for 18% (34) and nasal for 7% (13). 52% (97) were Brown class 2 defects. Forty-five patients were managed by obturation and 78% (142/183) had free tissue transfer. The main flaps used were radial (52), anterolateral thigh (27), DCIA (22), scapula (13) and fibula (11). There were significant changes over time regarding reconstruction type, use of primary implants, type of dental restoration, and length of hospital stay. Overall survival after 24 months was 64% (SE 4%) and after 60 months was 42% (SE 4%).

Conclusion

These data reflect a shift in the reconstruction of the maxillary defect afforded by the utilisation of zygomatic implants.
Tau positron emission tomography, cerebrospinal fluid and plasma biomarkers of neurodegeneration, and neurocognitive testing: an exploratory study of participants with myotonic dystrophy type 1
Authors: Laforce Robert Jr , Dallaire-Théroux Caroline , Racine Annie M. , Dent Gersham , Salinas-Valenzuela Cristian , Poulin Elizabeth , Cayer Anne-Marie , Bédard-Tremblay Daphnée , Rouleau-Bonenfant Thierry , St-Onge Frédéric , Schraen-Maschke Susanna , Beauregard Jean-Mathieu , Sergeant Nicolas , Puymirat Jack
Published: February 2022

Objective

To investigate Tau pathology using multimodal biomarkers of neurodegeneration and neurocognition in participants with myotonic dystrophy type 1 (DM1).

Methods

We recruited twelve participants with DM1 and, for comparison, two participants with Alzheimer’s Disease (AD). Participants underwent cognitive screening and social cognition testing using the Dépistage Cognitif de Québec (DCQ), among other tests. Biomarkers included Tau PET with [18F]-AV-1451, CSF (Aβ, Tau, phospho-Tau), and plasma (Aβ, Tau, Nf-L, GFAP) studies.

Results

Of the twelve DM1 participants, seven completed the full protocol (Neurocognition 11/12; PET 7/12, CSF 9/12, plasma 12/12). Three DM1 participants were cognitively impaired (CI). On average, CI DM1 participants had lower scores on the DCQ compared to cognitively unimpaired (CU) DM1 participants (75.5/100 vs. 91.4/100) and were older (54 vs. 44 years old) but did not differ in years of education (11.3 vs. 11.1). The majority (6/7) of DM1 participants had no appreciable PET signal. Only one of the CI participants presented with elevated Tau PET SUVR in bilateral medial temporal lobes. This participant was the eldest and most cognitively impaired, and had the lowest CSF Aβ 1-42 and the highest CSF Tau levels, all suggestive of co-existing AD. CSF Tau and phospho-Tau levels were higher in the 3 CI compared to CU DM1 participants, but with a mean value lower than that typically observed in AD. Nf-L and GFAP were elevated in most DM1 participants (9/11 and 8/11, respectively). Finally, CSF phospho-Tau was significantly correlated with plasma Nf-L concentrations.

Conclusions and relevance

We observed heterogenous cognitive and biomarker profiles in individuals with DM1. While some participants presented with abnormal PET and/or CSF Tau, these patterns were highly variable and only present in a small subset. Although DM1 may indeed represent a non-AD Tauopathy, the Tau-PET tracer used in this study was unable to detect an in vivo Tau DM1 signature in this small cohort. Interestingly, most DM1 participants presented with elevated plasma Nf-L and GFAP levels, suggestive of other, possibly related, central brain alterations which motivate further research. This pioneering study provides novel insights towards the potential relationship between biomarkers and neurocognitive deficits commonly seen in DM1.
Properties of the epileptiform activity in the cingulate cortex of a mouse model of LIS1 dysfunction
Authors: Domínguez-Sala E. , Andreu-Cervera A. , Martín-Climent P. , Murcia-Ramón R. , Martínez S. , Geijo-Barrientos Emilio
Published: February 2022

Dysfunction of the LIS1 gene causes lissencephaly, a drastic neurological disorder characterized by a deep disruption of the cortical structure. We aim to uncover alterations of the cortical neuronal networks related with the propagation of epileptiform activity in the Lis1/sLis1 mouse, a model lacking the LisH domain in heterozygosis. We did extracellular field-potential and intracellular recordings in brain slices of the anterior cingulate cortex (ACC) or the retrosplenial cortex (RSC) to study epileptiform activity evoked in the presence of bicuculline (10 µM), a blocker of GABAA receptors. The sensitivity to bicuculline of the generation of epileptiform discharges was similar in wild type (WT) and Lis1/sLis1 cortex (EC50 1.99 and 2.24 µM, respectively). In the Lis1/sLis1 cortex, we observed a decreased frequency of the oscillatory post-discharges of the epileptiform events; also, the propagation of epileptiform events along layer 2/3 was slower in the Lis1/sLis1 cortex (WT 47.69 ± 2.16 mm/s, n = 25; Lis1/sLis1 37.34 ± 2.43 mm/s, n = 15; p = 0.004). The intrinsic electrophysiological properties of layer 2/3 pyramidal neurons were similar in WT and Lis1/sLis1 cortex, but the frequency of the spontaneous EPSCs was lower and their peak amplitude higher in Lis1/sLis1 pyramidal neurons. Finally, the propagation of epileptiform activity was differently affected by AMPA receptor blockers: CNQX had a larger effect in both ACC and RSC while GYKI53655 had a larger effect only in the ACC in the WT and Lis1/sLis1 cortex. All these changes indicate that the dysfunction of the LIS1 gene causes abnormalities in the properties of epileptiform discharges and in their propagation along the layer 2/3 in the anterior cingulate cortex and in the restrosplenial cortex.
Mutations in the heparan sulfate backbone elongating enzymes EXT1 and EXT2 have no major effect on endothelial glycocalyx and the glomerular filtration barrier
Authors: Khalil Ramzi , Boels Margien G. S. ,   PALGA Group, Bezuijen A. , Boers J. E. , de Bruin P. C. , van Dijk M. A. A. M. , Drillenburg P. , Hamel A. F. , Hazelbag H. M. , Jonges G. N. , Kibbelaar R. E. , Lam K. H. , van der Linden H. , van Marsdijk J. , Meijer C. , Nagtegaal I. D. , Oudejans J. J. , Roelofs J. J. T. H. , Rozendaal L. , Sastrowijoto S. H. , Smits M. M. , Stavast J. , van den Berg Bernard M. , Bruijn Jan A. , Rabelink Ton J. , Hogendoorn Pancras C. W. , Baelde Hans J.
Published: February 2022

In this study, the effect of heterozygous germline mutations in the heparan sulfate (HS) glycosaminoglycan chain co-polymerases EXT1 and EXT2 on glomerular barrier function and the endothelial glycocalyx in humans is investigated. Heparan sulfate (HS) glycosaminoglycans are deemed essential to the glomerular filtration barrier, including the glomerular endothelial glycocalyx. Animal studies have shown that loss of HS results in a thinner glycocalyx. Also, decreased glomerular HS expression is observed in various proteinuric renal diseases in humans. A case report of a patient with an EXT1 mutation indicated that this could result in a specific renal phenotype. This patient suffered from multiple osteochondromas, an autosomal dominant disease caused by mono-allelic germline mutations in the EXT1 or EXT2 gene. These studies imply that HS is indeed essential to the glomerular filtration barrier. However, loss of HS did not lead to proteinuria in various animal models. We demonstrate that multiple osteochondroma patients do not have more microalbuminuria or altered glycocalyx properties compared to age-matched controls (n = 19). A search for all Dutch patients registered with both osteochondroma and kidney biopsy (n = 39) showed that an EXT1 or EXT2 mutation does not necessarily lead to specific glomerular morphological phenotypic changes. In conclusion, this study shows that a heterozygous mutation in the HS backbone elongating enzymes EXT1 and EXT2 in humans does not result in (micro)albuminuria, a specific renal phenotype or changes to the endothelial glycocalyx, adding to the growing knowledge on the role of EXT1 and EXT2 genes in pathophysiology.
Whole-crown 13C-pulse labelling in a sub-arctic woodland to target canopy-specific carbon fluxes
Authors: Friggens Nina L. , Hartley Iain P. , Grant Helen K. , Parker Thomas C. , Subke Jens-Arne , Wookey Philip A.
Published: February 2022

Key message

Whole-crown 13C-pulse labelling can target tree canopy C fluxes in regions with dense understorey cover and investigate how increased photosynthetic C inputs may affect whole-ecosystem C fluxes.

Climate change-driven increases in plant productivity have been observed at high northern latitudes. These trends are driven, in part, by the increasing abundance of tall shrub and tree species in arctic ecosystems, and the advance of treelines. Higher plant productivity may alter carbon (C) allocation and, hence, ecosystem C cycling and soil C sequestration. It is important to understand the contributions that the newly established canopy forming overstorey species makes to C cycling in these ecosystems. However, the presence of a dense understorey cover makes this challenging, with established partitioning approaches causing disturbance and potentially introducing measurement artefacts. Here, we develop an in situ whole-crown 13C-pulse labelling technique to isolate canopy C fluxes in areas of dense understorey cover. The crowns of five mountain birch (Betula pubescens ssp. czerepanovii) trees were provided with a 13CO2 pulse using portable field equipment, and leaf samples were collected from neighbouring con-specific trees and hetero-specific understorey shrubs on days 1–10 and 377 post-crown labelling. We found effective and long-term enrichment of foliage in labelled trees, but no evidence of the 13C-signal in con- or hetero-specific neighbouring trees or woody shrubs. This method is promising and provides a valuable tool to isolate the role of canopy tree species in ecosystems with dense understorey cover.
Physics-based Residual Kriging for dynamically evolving functional random fields
Authors: Peli Riccardo , Menafoglio Alessandra , Cervino Marianna , Dovera Laura , Secchi Piercesare
Published: February 2022

We present a novel approach named Physics-based Residual Kriging for the statistical prediction of spatially dependent functional data. It incorporates a physical model—expressed by a partial differential equation—within a Universal Kriging setting through a geostatistical modelization of the residuals with respect to the physical model. The approach is extended to deal with sequential problems, where samples of functional data become available along consecutive time intervals, in a context where the physical and stochastic processes generating them evolve, as time intervals succeed one another. An incremental modeling is used to account for both these dynamics and the misfit between previous predictions and actual observations. We apply Physics-based Residual Kriging to forecast production rates of wells operating in a mature reservoir according to a given drilling schedule. We evaluate the predictive errors of the method in two different case studies. The first deals with a single-phase reservoir where production is supported by fluid injection, while the second considers again a single-phase reservoir but the production is driven by rock compaction.
Low-dose CBCT imaging of alveolar buccal bone adjacent to mandibular anterior teeth— a pilot study
Authors: Ruetters Maurice , Gehrig Holger , Kronsteiner Dorothea , Doll Sara , Kim Ti-Sun , Lux Christopher J. , Sen Sinan
Published: February 2022

Objectives

Accurate description of buccal bone adjacent to mandibular anterior teeth is helpful for planning and monitoring periodontal and orthodontic treatment. Low-dose cone beam computed tomography (LD-CBCT) imaging has shown promising results for very small dental structures in animals. This study asserts that LD-CBCT is sufficiently accurate to measure buccal alveolar bone adjacent to human mandibular anterior teeth.

Materials and methods

Buccal bone level adjacent to 16 mandibular anterior teeth from four human cadavers was measured radiographically using one high-dose (HD) CBCT protocol and two LD-CBCT protocols. The resulting radiographic measurements of buccal bone height (bl) and thickness (bt) were compared with reference probe and reflected-light microscopy measurements. Measurement medians and Bland–Altman plots were calculated, and a linear mixed model was used to compare raters and imaging modalities.

Results

All regression coefficients were approximately 0, indicating high interrater, intrarater, and intermodality agreement. No significant differences were found between reference measurements and CBCT protocols. The mean differences for bl measurements were 0.07 mm (rater 1 [r1]) and 0.12 mm (rater 2 [r2]) for HD-CBCT; 0.07 mm (r1) and 0.13 mm (r2) for LD-CBCT-1; and 0.02 mm (r1) and 0.01 mm (r2) for LD-CBCT-2. For bt measurements, mean differences were 0.02 mm (r1) and 0.02 mm (r2) for HD-CBCT; 0.01 mm (r1) and 0.01 mm (r2) for LD-CBCT-1; and 0.00 mm (r1) and 0.01 mm (r2) for LD-CBCT-2.

Conclusions

Within the limitations of the present study, LD-CBCT seems to be a precise method for describing buccal bone and its thickness adjacent to mandibular anterior teeth in this experimental setting.

Clinical relevance

For the first time, this study showed LD-CBCT produces excellent results and is a reliable modality for imaging buccal bone in vitro. If clinical studies confirm these results, LD-CBCT could enable better treatment planning and monitoring at a radiation dose that is far lower than that of conventional HD-CBCT but similar to that of panoramic views.
Efficacy of nano-hydroxyapatite on caries prevention—a systematic review and meta-analysis
Authors: Wierichs Richard Johannes , Wolf Thomas G. , Campus Guglielmo , Carvalho Thiago S.
Published: February 2022

Introduction/objectives

The review systematically explored in vivo or in situ studies investigating the efficacy of nano-hydroxyapatite (nHA) to reduce initiation of or to remineralize initial caries lesions.

Data

Prospective controlled (non-)randomized clinical trials investigating the efficacy of a nHA compared to any other (placebo) treatment or untreated/standard control.

Sources

Three electronic databases (Central Cochrane, PubMed-MEDLINE, Ovid EMBASE) were screened. Outcomes were, e.g., ICDAS score, laser fluorescence, enamel remineralization rate, mineral loss, and lesion depth. No language or time restrictions were applied. Risk of bias and level of evidence were graded using the Risk of Bias 2.0 tool and GRADE profiler.

Study selection/results

Five in vivo (and 5 in situ) studies with at least 633 teeth (1031 specimens) being assessed in more than 420 (95) patients were included. No meta-analysis could be performed for in vivo studies due to the high heterogeneity of the study designs and the variety of outcomes. In situ studies indicate that under demineralization conditions, NaF was able to hinder demineralization, whereas nHA did not; simultaneously, nHA did not differ from the fluoride-free control. In contrast, under remineralizing conditions, nHA and NaF show the same remineralizing potential. However, the level of evidence was very low. Furthermore, six studies showed a high risk of bias, and six studies were funded/published by the manufacturers of the tested products.

Conclusion

The low number of clinical studies, the relatively short follow-up periods, the high risks of bias, and the limiting grade of evidence do not allow for conclusive evidence on the efficacy of nHA.

Clinical relevance

No conclusive evidence on the efficacy of nHA could be obtained based on the low number of clinical studies, the relatively short follow-up periods, the high risks of bias, the limiting grade of evidence, and study conditions that do not reflect the everyday conditions.
Pasteurella species bloodstream infections in Queensland, Australia, 2000–2019
Authors: Laupland Kevin B. , Stewart Adam G. , Edwards Felicity , Harris Patrick , Heney Claire , George Narelle , Coulter Sonali , Paterson David L.
Published: February 2022

Pasteurella species are infrequent but potentially severe causes of bloodstream infection (BSI). The objective of this study was to determine the incidence, risk factors, and outcomes of Pasteurella species BSI in a large Australian population. Retrospective, laboratory-based surveillance was conducted in Queensland, Australia (population ≈ 5 million) during 2000–2019, and clinical and outcome information was established by linkage to state hospital admissions and vital statistics databases. During more than 86 million person-years of surveillance, 272 incident Pasteurella species BSI occurred for an overall age- and sex-standardized annual incidence of 3.3 per million residents. The incidence of Pasteurella species BSI was highest in recent years and older individuals were at greatest risk. The median (interquartile range) Charlson Comorbidity Index was 2 (0–4) with scores of zero, 1, 2, and 3 + observed in 81 (30%), 37 (14%), 44 (16%), and 110 (40%) of cases. The 30-day all-cause case fatality was 9% (24/272) and patients who died had more comorbidities and were less likely to have community-associated disease. Although Pasteurella species are infrequent causes of BSI, older individuals and those with comorbidities are at highest risk. The burden of this disease may be expected to increase with an aging and more comorbid population.