bluuebunny/crossref_metadata_2025 huggingface dataset:
Coping strategies, emotional distress and perceived disease severity in a cohort of patients with rheumatoid arthritis: a mediation analysis
Authors: Tosato Sarah , Bonetto Chiara , Zanini Alice , Montanari Ilaria , Piccinelli Anna , Bixio Riccardo , Rossini Maurizio , Pacenza Giulio , Cristofalo Doriana , Fracassi Elena , Carletto Antonio
Published: August 2022

Objectives

Few data are available on the role of emotional distress as a possible mediator of the relationship between coping strategies and the Patient Global Assessment (PGA). This study aims to investigate, in a large cohort of patients affected by RA, the relationship between specific copying strategies and PGA, and the role of emotional distress as a mediator.

Methods

A total of 490 patients with RA completed a set of standardized assessments including the self-reported PGA, the Coping Orientation to the Problems Experienced (COPE-NVI) and the Hospital Anxiety and Depression Scale (HADS). A mediation analysis was conducted to investigate the role of emotional distress.

Results

The effect of coping strategies on the PGA score was significantly mediated by the emotional distress for religious (total effect mediated 42.0%), planning (total effect mediated 17.5%), behavioural disengagement (total effect mediated 10.5%), and focus on and venting of emotions (total effect mediated 9.8%). Seven coping strategies (acceptance, positive reinterpretation and growth, active coping, denial, humour, substance use-mental disengagement) resulted directly associated to PGA total score, but no mediation effect was found. The remaining four coping strategies were not associated to the PGA score.

Conclusion

This study suggests that coping strategies could be an important factor in the perceived disease severity. Consequently, in order to reduce PGA in patients with RA, a useful tool could be represented by the implementation of psychological interventions aiming to modify the specific coping styles. Moreover, to prevent or treat emotional distress seems to further reduce PGA.
Clinical trial transparency regulations: Implications to various scholarly publishing stakeholders
Authors: Abdul Razack Habeeb Ibrahim , Aranjani Jesil Mathew , Mathew Sam T
Published: August 2022

As thousands of 2019 Corona virus disease (Covid-19) clinical trials are continuously getting added to various registries these days, good practices on data sharing and transparency have become one of the prime topics of discussion than ever before. Although trial registration is considered a crucial step, there is a lack of integration between registration and published literature. Trial outcomes are a matter of public interest, but sponsor compliances are not adequate with the recommended guidelines. Although the global recognition of data transparency increases day by day, there is still a long journey to travel. It is high time that scholarly publishing stakeholders should put in a collaborative effort to check author compliance. In this article, we aimed to comprehend and discuss the imperative roles of various scholarly publishing stakeholders in improving clinical trial transparency during this pandemic situation and highlight the changing paradigm towards the pressing need for reporting clinical trial data more effectively.
Integrating Gender-Based Analysis Plus into Policy Responses to COVID-19: Lived Experiences of Lockdown in British Columbia, Canada
Authors: Smith Julia , Mũrage Alice , Lui Ingrid , Morgan Rosemary
Published: August 2022

Recognition of the differential effects of COVID-19 on women has led to calls for greater application of gender-based analysis within policy responses. Beyond pointing out where such policies are implemented, there is little analysis of the effects of efforts to integrate gender-based analysis into the COVID-19 response. Drawing on interviews informing a lived experienced approach to policy analysis, this article asks if, how, and to what effect gender-based analysis was implemented within social and economic policy responses during the initial lockdown, in British Columbia, Canada. It finds that, despite a rhetorical commitment to gender-based analysis, policies failed to address everyday inequalities.
Transplanting larch trees into warmer areas increases the photosynthesis and its temperature sensitivity
Authors: Ju Yali , Wang Chuankuan , Wang Nan , Quan Xiankui
Published: August 2022

To investigate the effects of climate warming on photosynthesis, Dahurian larch (Larix gmelinii Rupr.) trees from four sites (spanning ~ 5.5° in latitude and ~4 °C of warming) within the geographic range in China were transplanted into a common garden close to the warmer border in 2004. Throughout the growing season of 2018, the CO2- and temperature-response curves of the photosynthesis in the common garden and at the original sites were measured. It was discovered that warming treatment considerably increased the maximum net photosynthetic rate (Amax) by 23.4–35.3% depending on the sites, signifying that warming upregulated Amax with respect to the degree of warming. At 25 °C, warming enhanced the maximum Rubisco carboxylation rate (Vcmax), maximum electron transport rate (Jmax), and mass-based leaf nitrogen concentration (Nmass). The climate warming effect (CWE) on Amax was positively associated with the CWEs on Vcmax, Jmax and Nmass, which indicated that warming promoted Amax primarily via increasing carboxylation and photosynthetic electron transport rates and leaf nitrogen supply. The CWE in optimal photosynthetic temperature (Topt) was significant for the trees from the northern sites rather than the southern sites; however, the effect vanished for the trees transplanted to the common garden; this implied that Topt exhibited limited local thermal acclimation. Nevertheless, warming narrowed the temperature-response curve, the effect of which was positively associated with the warming magnitude. These findings implied that trees transplanted into warmer areas changed the photosynthetic optimum temperature and sensitivity. In summary, our results deepen the understanding of the underlying mechanisms of intraspecific responses of photosynthesis to temperature changes, including which of the modeling would improve the prediction of tree growth and forest carbon cycling under climate warming.
The Assessment of Social Determinants of Health in Postsepsis Mortality and Readmission: A Scoping Review
Authors: Hilton Ryan S. , Hauschildt Katrina , Shah Milan , Kowalkowski Marc , Taylor Stephanie
Published: July 2022

OBJECTIVE:

To summarize knowledge and identify gaps in evidence about the relationship between social determinants of health (SDH) and postsepsis outcomes.

DATA SOURCES:

We conducted a comprehensive search of PubMed/Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, and the Cochrane Library.

STUDY SELECTION:

We identified articles that evaluated SDH as risk factors for mortality or readmission after sepsis hospitalization. Two authors independently screened and selected articles for inclusion.

DATA EXTRACTION:

We dual-extracted study characteristics with specific focus on measurement, reporting, and interpretation of SDH variables.

DATA SYNTHESIS:

Of 2,077 articles screened, 103 articles assessed risk factors for postsepsis mortality or readmission. Of these, 28 (27%) included at least one SDH variable. Inclusion of SDH in studies assessing postsepsis adverse outcomes increased over time. The most common SDH evaluated was race/ethnicity (n = 21, 75%), followed by payer type (n = 10, 36%), and income/wealth (n = 9, 32%). Of the studies including race/ethnicity, nine (32%) evaluated no other SDH. Only one study including race/ethnicity discussed the use of this variable as a surrogate for social disadvantage, and none specifically discussed structural racism. None of the studies specifically addressed methods to validate the accuracy of SDH or handling of missing data. Eight (29%) studies included a general statement that missing data were infrequent. Several studies reported independent associations between SDH and outcomes after sepsis discharge; however, these findings were mixed across studies.

CONCLUSIONS:

Our review suggests that SDH data are underutilized and of uncertain quality in studies evaluating postsepsis adverse events. Transparent and explicit ontogenesis and data models for SDH data are urgently needed to support research and clinical applications with specific attention to advancing our understanding of the role racism and racial health inequities in postsepsis outcomes.
Development and Preliminary Psychometric Testing of the Drake Atrial Electrogram Assessment Survey: DAEGAS
Authors: Drake Jeanette , Hanneman Sandra K. , McEwen Melanie M. , Ramirez Elda G. , Conti Vincent R.
Published: July 2022

Background

Critical care nurses who care for postoperative cardiac surgery patients need such specialty knowledge as atrial electrograms (AEGs). An inadequate audit trail exists for psychometric performance of instruments to measure knowledge of AEGs.

Objectives

The aim of this study was to revise a previously tested instrument and assess evidence for content validity (content validity index), internal consistency (Cronbach α), and stability (correlation coefficient, r) reliability against the a priori criterion of 0.80.

Methods

The multiple-choice response, self-administered, paper-and-pencil instrument was revised to 20 items and named the Drake Atrial Electrogram Assessment Survey (DAEGAS). A panel of 6 AEG experts reviewed the DAEGAS for content validity evidence. The instrument was further revised to 19 items (13 knowledge and 6 AEG interpretation) and tested with 76 critical care nurses from the greater Houston metropolitan area.

Results

The content validity index was 0.93. Cronbach α was .51, and test-retest r was 0.74. Cronbach α increased to .60 and r was 0.73 with removal of 3 items: 2 items with a negative item-total correlation and 1 item that was transitioned to a sample question.

Discussion

Content validity evidence exceeded the a priori criterion. Internal consistency and stability reliability estimates did not meet the criterion, albeit the latter met the criterion recommended by psychometricians for a new instrument. Recommendations include further development of the DAEGAS to improve internal consistency estimates and testing for evidence of other forms of validity. Reliable and valid assessment of critical care nurse knowledge of AEGs will require improved psychometric performance of the DAEGAS.
Depth of Upper Lid Crease Construction in Asian Blepharoplasty
Authors: Chen William P. D.
Published: July 2022

The elegance of retrospective analysis of crease construction based on the levels of attachment is that it may be used to correlate a crease’s construction method with an outcome of crease depth based on medical record review. It expands on the current knowledge beyond simply describing a crease as being superficial or deep, and is useful for objective analysis of a technique’s merit.
Complex Nasal Reconstruction in a Wide-awake Ambulatory Setting: A Study of Efficacy and Perioperative Patient Experience
Authors: St. Denis-Katz Hannah N. , Bastianelli Michael , Macdonald Jillian , Zhang Jing
Published: July 2022

Background:

The use of local anesthesia in nasal surgery has gained popularity as a cost-effective and safe alternative. With the potential benefit of reconstruction without using general anesthesia, the goal of the study was to evaluate the patient-reported experience in addition to surgical outcomes and perioperative complications.

Methods:

A mixed-methods study was completed with retrospective chart review and patient-reported outcome questionnaire. The primary outcome measures were demographics, oncologic and surgical details, and postoperative complications. Secondary outcome measures were aesthetic outcomes and procedure tolerance, which were gathered from the FACE-Q questionnaire.

Results:

Of the 22 patients who met inclusion criteria, nine patients (41%) had forehead flaps performed and 13 patients (59%) had multilayer reconstruction with local flaps and cartilage grafts. The average number of surgeries performed, including revisions, was 2.3 ± 0.2. The overall complication rate for reconstructions and revisions was 20%, most of these were minor complications. The overall subjective rating of patient’s appearance was excellent with an average score of 83.9 (± 17.3) out of 100. There was minimal appearance distress as a product of the surgery with an average score of 84.9 (±18.8). On a scale of one to five, patients reported an average of 4.3 for convenience, 3.8 for efficiency of setup and procedure, and 3.4 out of 5 for comfortability with having an operation performed on their face wide awake.

Conclusion:

Our study demonstrated that complex nasal reconstruction performed under local anesthetic in a minor procedure setting is a feasible and safe option with good patient-reported outcomes.
An update on rib grafting in rhinoplasty: which rib is right?
Authors: Drake Virginia E. , Mowery Alia J. , Nellis Jason C.
Published: July 2022

Purpose of review

In revision or posttraumatic rhinoplasty, the quantity and quality of septal cartilage available for grafting is often deficient and auricular cartilage often provides insufficient strength for structural nasal reconstruction. Accordingly, rib cartilage serves as a reliable, abundant source of cartilage for grafting. However, the various sources of rib cartilage carry respective benefits and weaknesses. This review examines recent studies, novel applications and a comparison of the primary sources of rib cartilage, including autologous cartilage, irradiated cadaveric rib and fresh frozen cadaveric cartilage.

Recent findings

Options for rib cartilage include autologous, irradiated cadaveric rib, and more recently, reports on fresh frozen cadaveric cartilage. Studies continue to conclude that autologous and irradiated donor cartilage carry equivalent results, have similar rates of complication and have a comparable cost profile.

Regardless of the source, rib cartilage plays an important role in structural rhinoplasty, especially in revision cases. Although the risks, benefits and long-term results of autologous and radiated homologous cartilage have been evaluated in observational studies, fresh frozen rib cartilage will need further follow up before widespread use, although preliminary literature shows promise.
Patient-specific implants in orbital reconstruction
Authors: Hajibandeh Jeffrey , Lee Cameron
Published: July 2022

Purpose of review

Advances in the use of patient-specific implants (PSIs) and virtual surgical planning (VSP) for reconstruction of primary and secondary traumatic orbital defects are explored.

Recent findings

PSIs and VSP are emerging technologies that promise to make complex orbital reconstructions safer and more predictable for patients. Recent studies highlight principles of implant design, the novel use of multiunit implant constructs, and utility of intraoperative imaging adjuncts to achieve favorable outcomes.

This article summarizes recent developments in PSIs for orbital reconstruction. A complete workflow including presurgical planning, execution in the operating room, postoperative analysis, and avoidance of common pitfalls and implant design errors are reviewed.
Enhanced Recovery after Surgery (ERAS) protocols in craniomaxillofacial surgery: an evidence-based review
Authors: Obayemi Adetokunbo , Tatum Sherard A.
Published: July 2022

Purpose of review

Enhanced Recovery after Surgery (ERAS) refers to a patient centered, multidisciplinary team developed pathway aimed at reducing the surgical stress response and facilitating expedited patient postoperative recovery. These protocols have been largely developed in the general surgery literature and have led to vast improvements in the patient experience. With a growing shortage of hospital resources during the height of the COVID-19 pandemic there has been a growing push to apply these principles to a wide variety of specialties.

Recent findings

ERAS protocols are generally substantiated on three phases along the continuum of surgical care: preadmission optimization, intraoperative treatment, and postoperative management. In this article, the evidence for ERAS development in craniomaxillofacial surgery will be reviewed, and recommendations from prior studies for enhanced recovery will be outlined.

ERAS protocols have been proven effective in many surgical arenas, however, modification is needed for the craniomaxillofacial population. The implications for widespread implementation of ERAS protocols during these procedures are a potentially shortened length of stay, expedited early return to function, reduction in narcotic dependence, and reduction in postdischarge complications necessitating additional intervention.
The use of race-based terminology in the rhinoplasty literature
Authors: Newsome Hillary A. , Chi John J.
Published: July 2022

Purpose of review

To provide an overview of the use of race-based terminology in the rhinoplasty literature.

Recent findings

The rhinoplasty literature is often indexed by race, with common usage of the terms Ethnic/Non-Caucasian/Nonwhite; African American/of African descent; Hispanic/Latinx; and Asian to refer to certain patient populations. There are wide variations in facial features within these populations, but specific traits may be more prevalent in patients with certain backgrounds. More recently, in particular within the ‘Asian rhinoplasty’ literature, titles have pivoted to include specific anatomic characteristics of interest, which offers a more objective way of discussing this topic.

The use of race and ethnicity to describe facial and nasal anatomy in the rhinoplasty literature introduces subjectivity and diminishes the validity of the rhinoplasty literature. We advocate the usage of specific physical and anatomic descriptions rather than race and ethnicity within the rhinoplasty literature.
Laryngeal trauma: a review of current diagnostic and management strategies
Authors: Iarocci Andrew L. , Winters Ryan D.
Published: July 2022

Purpose of review

The purpose of this review is to provide the most up to date information on evaluation and management of laryngeal trauma.

Recent findings

Timely diagnosis and proper treatment of laryngeal fractures are imperative for preserving a functional larynx. This review will focus on evaluation and management strategies

The larynx provides significant functions including respiration, phonation, and airway protection. Algorithms have been developed in order to standardize the evaluation and management of these injuries to preserve a functional larynx. Physicians must diagnose and treat these laryngeal traumas in a timely fashion in order to prevent morbidity and, rarely, mortality.
Dental outcomes after neonatal mandibular distraction
Authors: Morris Lisa
Published: July 2022

Purpose of review

The aim of this study was to understand dental complications associated with neonatal mandibular distraction and subsequent dental outcomes.

Recent findings

Dental injury is often associated with neonatal mandibular distraction osteogenesis. Newer technology offers safer techniques to minimize this risk. Long-term follow up and dental outcomes in permanent dentition are needed to better understand the actual risk associated with the procedure.

Surgeons performing neonatal mandibular distraction osteogenesis need to understand the associated risks to deciduous and permanent dentition as well as techniques to mitigate this risk.
Long-Term Pulmonary Outcomes in Children Mechanically Ventilated for Severe Bronchiolitis*
Authors: de Sonnaville Eleonore S. V. , Knoester Hennie , Terheggen-Lagro Suzanne W. J. , Kӧnigs Marsh , Oosterlaan Jaap , van Woensel Job B. M.
Published: July 2022

Objectives:

Bronchiolitis is a common indication for mechanical ventilation in the PICU. Both bronchiolitis and invasive mechanical ventilation may cause adverse long-term pulmonary outcomes. This study investigates children with a history of invasive mechanical ventilation for bronchiolitis, addressing: 1) the extent, 2) potential explanatory factors, and 3) possible impact on daily life activities of adverse long-term pulmonary outcomes.

Design:

Single-center cohort study.

Setting:

Outpatient PICU follow-up clinic.

Patients:

Children 6–12 years old with a history of invasive mechanical ventilation for bronchiolitis (age <2 yr).

Interventions:

None.

Measurements and Main Results:

Long-term pulmonary outcomes were assessed by a standardized questionnaire and by spirometry. Nineteen out of 74 included children (26%) had adverse long-term pulmonary outcomes, of whom the majority had asthma (14/74, 19%). By logistic regression analysis, we assessed whether background characteristics and PICU-related variables were associated with long-term pulmonary outcomes. In general, we failed to identify any explanatory factors associated with adverse long-term pulmonary outcomes. Nonetheless, atopic disease in family and longer duration of invasive mechanical ventilation (days) were associated with greater odds of having asthma at follow-up (odds ratio, 6.4 [95% CI, 1.2–36.0] and 1.3 [95% CI, 1.0–1.7], respectively). Adverse pulmonary outcome at follow-up was associated with more frequent use of pulmonary medication after PICU discharge. In comparison with those without adverse pulmonary outcomes, we did not identify any difference in frequency of sports performance or school absenteeism.

Conclusions:

In this single-center cohort, one-quarter of the children attending follow-up with a history of invasive mechanical ventilation for bronchiolitis had adverse, mostly previously undetected, long-term pulmonary outcomes at 6–12 years. Atopic disease in family and longer duration of invasive mechanical ventilation were associated with presence of asthma. The presence of adverse pulmonary outcomes was associated with more frequent use of pulmonary medication after PICU discharge.
The Epidemiology of Pediatric Autoimmune Hepatitis in Scotland: A National Cohort Study
Authors: Sutton Harry , Tayler Rachel , Chalmers Iain , Cowieson Jennifer , Fraser Karen , Henderson Paul , Hansen Richard
Published: July 2022

Objectives:

Autoimmune hepatitis (AIH) is a rare, but potentially severe, cause of liver disease in children. We aimed to summarize how children with AIH in Scotland presented, were investigated and managed in addition to producing novel epidemiological data and outcomes.

Methods:

All prevalent pediatric patients with AIH cared for in pediatric services between January 2013 and September 2018 were included. Individual patient data were obtained from electronic patient records in the 3-main academic pediatric centers in Scotland covering the entire population.

Results:

Thirty-eight patients were included (25 female) with median follow-up of 33 months (range, 2–145 mo) and 136 total patient years. The incidence between 2014 and 2017 was 0.49/100 000/y (95% confidence interval, 0.29-0.78) and point prevalence between 2013 and 2018 was 1.75/100 000 (95% confidence interval, 1.42-2.13). Thirty-five (92%) patients were autoantibody positive, most commonly anti-nuclear antibody (63%) and anti-smooth muscle antibody (42%). Thirty-seven (97%) patients had induction therapy with oral corticosteroids, 30 (79%) required maintenance treatment with azathioprine, and 23 (61%) received ursodeoxycholic acid. There were 1.4 disease flares per 10 patient years and 3 patients required liver transplantation with an overall 5-year survival rate without the need for transplantation of 95%.

Conclusions:

We calculated a novel incidence and prevalence rate for pediatric AIH in Scotland. Nearly all were invariably treated initially with corticosteroids with most placed-on azathioprine as maintenance therapy. Outcomes were generally favorable with low rates of disease flares and the need for transplantation being rare.
William Gilbert Chaloner. 22 November 1928—13 October 2016
Authors: Crane Peter R. , Scott Andrew C. , Beerling David J.
Published: August 2022

William G. Chaloner, widely known as Bill, was a world leader in the study of plant fossils. He was a pioneer in the development of palaeopalynology and helped integrate studies of macroscopic plant fossils with investigations of fossil pollen and spores. His early work expanded our understanding of Carboniferous coal-forming plants and vegetation and his investigations on the changing distributions of fossil plants contributed to improved knowledge of biogeographic patterns during the late Paleozoic, including the concept of continental drift before it was widely accepted. Bill's relentless creativity demonstrated how the fossil record of plants could be exploited to reconstruct ancient climates. He also recognized that because certain structural features of fossil leaves directly record levels of the greenhouse gas carbon dioxide they are valuable ‘biosensors’ of ancient atmospheric composition allowing investigation of the link between the greenhouse effect and past warm climates. With his clear and critical mind and grasp of diverse subject matter, Bill was adept at distilling disparate information into a coherent and understandable whole. An engaging communicator, and an unfailingly supportive mentor, he inspired many young scientists during his five decades of service to colleges of the University of London.
A statistical method to optimize the chemical etching process of zinc oxide thin films
Authors: Lynes David D. , Chandrahalim Hengky , Brown Justin M. , Singh Karanvir , Bodily Kyle T. , Leedy Kevin D.
Published: August 2022

Zinc oxide (ZnO) is an attractive material for microscale and nanoscale devices. Its desirable semiconductor, piezoelectric and optical properties make it useful in applications ranging from microphones to missile warning systems to biometric sensors. This work introduces a demonstration of blending statistics and chemical etching of thin films to identify the dominant factors and interaction between factors, and develop statistically enhanced models on etch rate and selectivity of c-axis-oriented nanocrystalline ZnO thin films. Over other mineral acids, ammonium chloride (NH
4
Cl) solutions have commonly been used to wet etch microscale ZnO devices because of their controllable etch rate and near-linear behaviour. Etchant concentration and temperature were found to have a significant effect on etch rate. Moreover, this is the first demonstration that has identified multi-factor interactions between temperature and concentration, and between temperature and agitation. A linear model was developed relating etch rate and its variance against these significant factors and multi-factor interactions. An average selectivity of 73 : 1 was measured with none of the experimental factors having a significant effect on the selectivity. This statistical study captures the significant variance observed by other researchers. Furthermore, it enables statistically enhanced microfabrication processes for other materials.
A tale of two plasmids: contributions of plasmid associated phenotypes to epidemiological success among
Shigella
Authors: Malaka De Silva P. , Stenhouse George E. , Blackwell Grace A. , Bengtsson Rebecca J. , Jenkins Claire , Hall James P. J. , Baker Kate S.
Published: August 2022

Dissemination of antimicrobial resistance (AMR) genes by horizontal gene transfer (HGT) mediated through plasmids is a major global concern. Genomic epidemiology studies have shown varying success of different AMR plasmids during outbreaks, but the underlying reasons for these differences are unclear. Here, we investigated two
Shigella
plasmids (pKSR100 and pAPR100) that circulated in the same transmission network but had starkly contrasting epidemiological outcomes to identify plasmid features that may have contributed to the differences. We used plasmid comparative genomics to reveal divergence between the two plasmids in genes encoding AMR, SOS response alleviation and conjugation. Experimental analyses revealed that these genomic differences corresponded with reduced conjugation efficiencies for the epidemiologically successful pKSR100, but more extensive AMR, reduced fitness costs, and a reduced SOS response in the presence of antimicrobials, compared with the less successful pAPR100. The discrepant phenotypes between the two plasmids are consistent with the hypothesis that plasmid-associated phenotypes contribute to determining the epidemiological outcome of AMR HGT and suggest that phenotypes relevant in responding to antimicrobial pressure and fitness impact may be more important than those around conjugation in this setting. Plasmid phenotypes could thus be valuable tools in conjunction with genomic epidemiology for predicting AMR dissemination.
Encrypted federated learning for secure decentralized collaboration in cancer image analysis
Authors: Truhn Daniel , Arasteh Soroosh Tayebi , Saldanha Oliver Lester , Müller-Franzes Gustav , Khader Firas , Quirke Philip , West Nicholas P. , Gray Richard , Hutchins Gordon G. A. , James Jacqueline A. , Loughrey Maurice B. , Salto-Tellez Manuel , Brenner Hermann , Brobeil Alexander , Yuan Tanwei , Chang-Claude Jenny , Hoffmeister Michael , Foersch Sebastian , Han Tianyu , Keil Sebastian , Schulze-Hagen Maximilian , Isfort Peter , Bruners Philipp , Kaissis Georgios , Kuhl Christiane , Nebelung Sven , Kather Jakob Nikolas
Published: July 2022

Artificial Intelligence (AI) has a multitude of applications in cancer research and oncology. However, the training of AI systems is impeded by the limited availability of large datasets due to data protection requirements and other regulatory obstacles. Federated and swarm learning represent possible solutions to this problem by collaboratively training AI models while avoiding data transfer. However, in these decentralized methods, weight updates are still transferred to the aggregation server for merging the models. This leaves the possibility for a breach of data privacy, for example by model inversion or membership inference attacks by untrusted servers. Homomorphically encrypted federated learning (HEFL) is a solution to this problem because only encrypted weights are transferred, and model updates are performed in the encrypted space. Here, we demonstrate the first successful implementation of HEFL in a range of clinically relevant tasks in cancer image analysis on multicentric datasets in radiology and histopathology. We show that HEFL enables the training of AI models which outperform locally trained models and perform on par with models which are centrally trained. In the future, HEFL can enable multiple institutions to co-train AI models without forsaking data governance and without ever transmitting any decryptable data to untrusted servers.

One Sentence Summary

Federated learning with homomorphic encryption enables multiple parties to securely co-train artificial intelligence models in pathology and radiology, reaching state-of-the-art performance with privacy guarantees.
A randomized controlled trial on the effects of decision aids for choosing discharge destinations of older stroke patients
Authors: Aoki Yoriko , Nakayama Kazuhiro , Yonekura Yuki
Published: August 2022

In Japanese medical practice, older stroke survivors are bombarded with information regarding their discharge locations, increasing their decision-making difficulties. This study used a randomized controlled trial to evaluate the influence of using decision aids (DAs) matching the values of older stroke patients and their families on the internal conflict and participation in discharge destination decisions.

Participants were randomly allocated to intervention and control groups. The intervention lasted for two months, from admission to discharge, and a survey was conducted on both occasions. DAs were provided to the intervention group, and brochures to the control group. The decisional conflict scale (DCS) and the control preference scale (CPS) were the primary and secondary endpoints, respectively. An unpaired t-test and z-test analyzed inter-group differences in DCS, and CPS, respectively. This trial was registered with the University Hospital Medical Information Network (UMIN Registration No.: UMIN00032623), certified as a test registration institution by the World Health Organization.

Ninety-nine participants completed a full analysis set, which revealed that the intervention group had significantly more participants who had already decided on their discharge destination while they were admitted to the hospital. These were “the same place as before admission” in a significant number of cases. No significant inter-group differences were found in the DCS and CPS scores. DAs were effective at reducing uncertainty and controlling the decline in participation rates, especially in participants living alone who were unable to decide their discharge destination, and at clarifying the values of those aged 75 and older. The DA made it possible to increase available choices and explain the disadvantages regarding various locations of discharge destinations, allowing fewer internal conflicts in the decision-making process. Going forward, there is a need to further our understanding of methods of offering DA, the ideal duration of these interventions, and the identification of beneficiaries.
Systemic inflammatory syndromes as life-threatening side effects of immune checkpoint inhibitors: Systematic review of the literature
Authors: Liu Lisa L. , Skribek Marcus , Harmenberg Ulrika , Gerling Marco
Published: July 2022

Immune checkpoint inhibitors (ICIs) are associated with a wide range of immune-related adverse events (irAEs). As oncological indications for ICIs widen, their rare side effects become increasingly visible in clinical practice and impact therapy decisions.

Here, we provide a systematic review of the literature of CRS and related life-threatening side effects of ICI treatment, such as hemophagocytic lymphohistiocytosis (HLH). We searched Medline, Embase, and the Web of Science Core Collection from inception until October 2021 for reports on CRS, cytokine storm, macrophage activation syndrome, HLH, and related hyperinflammatory disorders in patients with solid cancers receiving ICIs. We found n = 1866 articles, which were assessed for eligibility independently by two examiners. Of those, n = 49 articles reporting on n = 189 individuals were eligible for review. We found that the median time from last infusion to the occurrence of CRS/HLH was approximately nine days, while the onset of symptoms varied from immediately after infusion to one month after treatment. Most patients were treated with either corticosteroids or the anti-interleukin 6 (IL-6) antibody tocilizumab, and although the majority of patients recovered, a few cases were fatal. Concomitant IL-6 and ICI treatment was reported as beneficial for both the antitumoral effect and for limiting side effects. Data from international pharmacovigilance databases underscored that ICI-related CRS and HLH are rare events, but we identified significant differences in reported frequencies, which might suggest substantial underreporting.

The results from this first systematic review of CRS/HLH due to ICI therapy highlight that life-threatening systemic inflammatory complications of ICIs are rare and non-fatal in the majority of patients. Limited data support the use of IL-6 inhibitors in combination with ICIs to augment the antitumoral effect and reduce hyperinflammation.
Institutional Trust in Times of Corona
Authors: Snel Erik , El Farisi Btissame , Engbersen Godfried , Krouwel André
Published: July 2022

During the corona pandemic, governments of all countries appealed strongly to the trust of their populations by implementing drastic social and economic measures to prevent the spread of the virus. This study seeks to understand mechanisms that influence the level of institutional trust at the time of the corona pandemic. We are specifically interested in how three explanatory factors (socioeconomic status, experienced economic insecurity and dissatisfaction with the implemented corona policies) can, in mutual association, explain differences in institutional trust. This study is based on data from a large-scale panel survey on the social impact of COVID-19, carried out by Kieskompas research agency (N=22,696). Using a serial mediation analysis, we show that SES has both a direct and indirect effect on the level of institutional trust. People with higher SES experience less economic insecurity and have less dissatisfaction with the corona policies and, partly as a result of this, stronger institutional trust. It is also true that economic insecurity increases dissatisfaction with the corona policies and, partly as a result of this, weakens the level of trust.
The effects of a 20-week exercise program on blood-circulating biomarkers related to brain health in children with overweight or obesity: The ActiveBrains project
Authors: Rodriguez-Ayllon María , Plaza-Florido Abel , Mendez-Gutierrez Andrea , Altmäe Signe , Solis- Urra Patricio , M. Aguilera Concepción , Catena Andrés , Ortega Francisco B. , Esteban-Cornejo Irene
Published: July 2022

Background

Emerging research supports that exercise positively affects neurodevelopment. However, the mechanisms linking exercise with brain health are largely unknown. We aimed to investigate the effect of exercise on (i) blood biomarkers selected based on previous evidence (brain-derived neurotrophic factor (BDNF), β-hydroxybutyrate (BHB), cathepsin B (CTSB), kynurenine, fibroblast growth factor 21 (FGF21), vascular cell adhesion molecule-1 (sVCAM-1)); and (ii) a panel of 92 neurology-related proteins (discovery analysis). We also investigated whether changes in these biomarkers mediate the effects of exercise on brain health (hippocampal structure and function, cognitive performance, and mental health).

Methods

81 children with overweight/obesity (10.1 ±1.1 years, 41% girls) were randomized to either 20-week of aerobic plus resistance exercise or control. Candidate biomarkers were assessed using ELISA for Kynurenine, FGF21, and CTSB, colorimetry for BHB, and XMap for BDNF and VCAM-1. The 92 neurology-related proteins were analyzed by antibody-based proteomic analyses.

Results

Our intervention had no significant effect on candidate biomarkers (all p>0.05). In the discovery analysis, a reduction in circulating macrophage scavenger receptor type-I (MSR1) was observed (standardized differences between groups (SMD): -0.3, p=0.001). This effect was validated using ELISA methods (SMD: -0.3, p=0.01). None of the biomarkers mediated the effects of exercise on brain health.

Conclusions

Our study does not support a chronic effect of exercise on candidate biomarkers. Nevertheless, we observed that chronic exercise reduced the levels of MRS1, while it did not mediate the effects of exercise on brain health. Future studies should explore the implications of this novel biomarker on general health.

Highlights

Candidate biomarkers (i.e., brain-derived neurotrophic factor (BDNF), β-hydroxybutyrate (BHB), cathepsin B (CTSB), kynurenine, fibroblast growth factor 21 (FGF21), vascular cell adhesion molecule-1 (sVCAM-1)) did not mediate the effects of exercise on brain health outcomes.

Our discovery analysis, a panel of 92 neurology-related proteins, identified a reduction effect of exercise on blood-circulating MRS1.

Exercise-induced changes in MRS1 did not mediate changes in brain health outcomes.

The MSR1 is a membrane glycoprotein, that has not been related to exercise before, expressed in macrophages, and involved in pathological processes such as atherosclerosis, non-alcoholic fatty liver disease, and neurological diseases.

Future studies should confirm the effect of exercise on MRS1 and its implications on general health.
The Efficacy of Facemasks in the Prevention of COVID-19: A Systematic Review
Authors: Alihsan Bedir , Mohammed Arrianna , Bisen Yash , Lester Janice , Nouryan Christian , Cervia Joseph
Published: July 2022

Facemasks have become a symbol of disease prevention in the context of COVID-19; yet, there still exists a paucity of collected scientific evidence surrounding their epidemiological efficacy in the prevention of SARS-CoV-2 transmission. This systematic review sought to analyze the efficacy of facemasks, regardless of type, on the prevention of SARS-CoV-2 transmission in both healthcare and community settings.

The initial review yielded 1732 studies, which were reviewed by three study team members. Sixty-one full text studies were found to meet entry criteria, and 13 studies yielded data that was used in the final analysis.

In all, 243 subjects were infected with COVID-19, of whom 97 had been wearing masks and 146 had not. The probability of getting COVID-19 for mask wearers was 7% (97/1463, p=0.002), for non-mask wearers, probability was 52% (158/303, p=0.94). The Relative Risk of getting COVID-19 for mask wearers was 0.13 (95% CI: 0.10-0.16).

Based on these results, we determined that across healthcare and community settings, those who wore masks were less likely to contact COVID-19. Future investigations are warranted as more information becomes available.
EARLY WARNING INDICATORS AT FACILITIES IN THE SOUTHERN HIGHLANDS REGION OF TANZANIA: LESSONS FOR HIV DRUG RESISTANCE SURVEILLANCE
Authors: Khamadi Samoel A , Mavere Caroline , Bahemana Emmanuel , Lwilla Anange , Mizinduko Mucho , Bwigane Seth , Peter Adela , Makando Joy , Peter Benjamin , Agaba Patricia , Shah Neha , Julu Boniphase , Ganesan Kavitha , Coakley Peter , Lee Elizabeth H.
Published: July 2022

Background

The World Health Organization early warning indicators (EWIs) permit surveillance of factors associated with the emergence of HIV drug resistance (HIVDR). We examined cross- and within-region performance on HIVDR EWIs for selected HIV care and treatment clinics (CTCs) in five regions of southern Tanzania.

Methods

In 2016, we retrospectively collected EWI data from 50 CTCs for the January to December 2013 period. EWIs included the following: on time ART pick-up, retention on ART, ARV stockouts, and pharmacy prescribing and dispensing practices. Data for pediatric and adult people living with HIV were abstracted from source files, and frequencies and proportions were calculated for each EWI overall, as well as stratified by region, facility, and age group.

Results

Across and within all regions, on average, on-time pick-up of pills (63.0%), retention on ART (76.0%), and pharmacy stockouts (69.0%) were consistently poor for the pediatric population. Similarly, on-time pill pick up (66.0%), retention on ART (72.0%) and pharmacy stockouts (53.0%) for adults were also poor. By contrast, performance on pharmacy prescribing and dispensing practices were as desired for both pediatric and adult populations with few facility-level exceptions.

Conclusion

In this study, regions and facilities in the southern highlands of Tanzania reported widespread presence of HIVDR risk factors, including sub-optimal timeliness of pill pickup, retention on ART, and drug stockouts. Routine EWI monitoring provides a check on quality of service delivery, as well as affordable, large-scale surveillance for HIVDR risk factors. EWI monitoring remains relevant particularly in the context of new ART drug roll-out such as dolutegravir, during the COVID-19 pandemic when resultant HIV service disruptions require careful monitoring, and for virologic suppression as countries move closer to epidemic control.
Nuclear myosin VI maintains replication fork stability
Authors: Shi Jie , Hauschulte Kristine , Mikicic Ivan , Maharjan Srijana , Arz Valerie , Heidelberger Jan B. , Schaefer Jonas V. , Dreier Birgit , Plückthun Andreas , Beli Petra , Ulrich Helle D. , Wollscheid Hans-Peter
Published: July 2022

The actin cytoskeleton is of fundamental importance for cellular structure and plasticity. However, abundance and function of filamentous (F-) actin in the nucleus are still controversial. Here we show that the actin-based molecular motor myosin VI contributes to the stabilization of stalled or reversed replication forks. In response to DNA replication stress, myosin VI associates with stalled replication intermediates and cooperates with the AAA ATPase WRNIP1 in protecting these structures from DNA2- mediated nucleolytic attack. Using nuclear localization sequence (NLS) and ubiquitin E3-fusion DARPins to manipulate myosin VI levels in a compartment-specific manner, we provide evidence for the direct involvement of myosin VI in the nucleus and against a contribution of the abundant cytoplasmic pool during the replication stress response.
ATM and MSH2 control blunt DNA end joining in immunoglobulin class switch recombination
Authors: Sible Emily , Attaway Mary , Fiorica Giuseppe , Michel Genesis , Chaudhuri Jayanta , Vuong Bao Q.
Published: July 2022

Class switch recombination (CSR) produces secondary immunoglobulin isotypes and requires AID-dependent DNA deamination of intronic switch (S) regions within the immunoglobulin heavy chain (Igh) gene locus. Non-canonical repair of deaminated DNA by mismatch repair (MMR) or base excision repair (BER) creates DNA breaks that permit recombination between distal S regions. ATM-dependent phosphorylation of AID at serine-38 (pS38-AID) promotes its interaction with APE1, a BER protein, suggesting that ATM regulates CSR through BER. However, pS38-AID may also function in MMR during CSR, although the mechanism remains unknown. To examine whether ATM modulates BER- and/or MMR-dependent CSR, Atm-/- mice were bred to mice deficient for the MMR gene Msh2. Surprisingly, the predicted Mendelian frequencies of Atm-/-Msh2-/- adult mice were not obtained. To generate ATM and MSH2-deficient B cells, Atm was conditionally deleted on an Msh2-/- background using a floxed ATM allele [Atmf] and B cell-specific Cre recombinase expression (CD23-cre) to produce a deleted ATM allele (AtmD). As compared to AtmD/Dand Msh2-/- mice and B cells, AtmD/DMsh2-/- mice and B cells display a reduced CSR phenotype. Interestingly, Sμ-Sγ1 junctions from AtmD/DMsh2-/-B cells that were induced to switch to IgG1 in vitro showed a significant loss of blunt end joins and an increase in insertions as compared to wildtype, AtmD/D, or Msh2-/- B cells. This data indicates that the absence of both ATM and MSH2 blocks non-homologous end joining (NHEJ), leading to inefficient CSR. We propose a model whereby ATM and MSH2 function cooperatively to regulate end-joining during CSR through pS38-AID.

Loss of the DNA repair genes Atm and Msh2 produces a novel synthetic lethality in mice. B cell specific deletion of Atm on an Msh2-/- background reduces Ig CSR and inhibits NHEJ.