bluuebunny/crossref_metadata_2025 huggingface dataset:
Whole-Genome Duplications and the Diversification of the Globin-X Genes of Vertebrates
Authors: Hoffmann Federico G , Storz Jay F , Kuraku Shigehiro , Vandewege Michael W , Opazo Juan C
Published: September 2021

Globin-X (GbX) is an enigmatic member of the vertebrate globin gene family with a wide phyletic distribution that spans protostomes and deuterostomes. Unlike canonical globins such as hemoglobins and myoglobins, functional data suggest that GbX does not have a primary respiratory function. Instead, evidence suggests that the monomeric, membrane-bound GbX may play a role in cellular signaling or protection against the oxidation of membrane lipids. Recently released genomes from key vertebrates provide an excellent opportunity to address questions about the early stages of the evolution of GbX in vertebrates. We integrate bioinformatics, synteny, and phylogenetic analyses to characterize the diversity of GbX genes in nonteleost ray-finned fishes, resolve relationships between the GbX genes of cartilaginous fish and bony vertebrates, and demonstrate that the GbX genes of cyclostomes and gnathostomes derive from independent duplications. Our study highlights the role that whole-genome duplications (WGDs) have played in expanding the repertoire of genes in vertebrate genomes. Our results indicate that GbX paralogs have a remarkably high rate of retention following WGDs relative to other globin genes and provide an evolutionary framework for interpreting results of experiments that examine functional properties of GbX and patterns of tissue-specific expression. By identifying GbX paralogs that are products of different WGDs, our results can guide the design of experimental work to explore whether gene duplicates that originate via WGDs have evolved novel functional properties or expression profiles relative to singleton or tandemly duplicated copies of GbX.
Necrosis-induced apoptosis promotes regeneration in Drosophila wing imaginal discs
Authors: Klemm Jacob , Stinchfield Michael J , Harris Robin E
Published: September 2021

Regeneration is a complex process that requires a coordinated genetic response to tissue loss. Signals from dying cells are crucial to this process and are best understood in the context of regeneration following programmed cell death, like apoptosis. Conversely, regeneration following unregulated forms of death, such as necrosis, have yet to be fully explored. Here, we have developed a method to investigate regeneration following necrosis using the Drosophila wing imaginal disc. We show that necrosis stimulates regeneration at an equivalent level to that of apoptosis-mediated cell death and activates a similar response at the wound edge involving localized JNK signaling. Unexpectedly, however, necrosis also results in significant apoptosis far from the site of ablation, which we have termed necrosis-induced apoptosis (NiA). This apoptosis occurs independent of changes at the wound edge and importantly does not rely on JNK signaling. Furthermore, we find that blocking NiA limits proliferation and subsequently inhibits regeneration, suggesting that tissues damaged by necrosis can activate programmed cell death at a distance from the injury to promote regeneration.
Risk Factors for Nonresilient Outcomes in Older Adults After Total Knee Replacement
Authors: Laskow Thomas , Zhu Jiafeng , Buta Brian , Oni Julius , Sieber Frederick , Bandeen-Roche Karen , Walston Jeremy , Franklin Patricia D , Varadhan Ravi
Published: September 2021

Background

Total knee replacement (TKR) is a common procedure in older adults. Physical resilience may be a useful construct to explain variable outcomes. We sought to define a simple measure of physical resilience and identify risk factors for nonresilient patient outcomes.

Methods

Secondary analysis of Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement (FORCE-TJR) cohort study, a prospective registry of total joint replacement. The analysis included 7 239 adults aged 60 or older who underwent TKR between 2011 and 2015. Measures included sociodemographic and health factors. Outcomes were categorized as physically resilient versus nonresilient based on the change from baseline to 1-year follow-up for 3 patient-reported outcomes: the physical component summary (PCS), bodily pain (BP), and vitality (VT) from the Short Form-36 subcomponent scores, at preop and 1-year postprocedure. Associations were expressed as relative risk (RR) of physically nonresilient outcomes using generalized linear regression models, with Poisson distribution and log link.

Results

Age, body mass index, and Charlson Comorbidity Index (CCI) were associated with increased risk of physically nonresilient outcomes across PCS, BP, and VT: age, per 5 years for PCS (RR = 1.18 [1.12–1.23]), BP (RR = 1.06 [1.01–1.11), and VT (RR = 1.09 [1.06–1.12]); body mass index, per 5 kg/m2, for PCS (RR = 1.13 [1.07–1.19]), BP (RR = 1.06 [1.00–1.11]), and VT (RR = 1.08 [1.04–1.11]); and CCI for PCS CCI = 1 (RR = 1.38 [1.20–1.59]), CCI = 2–5 (RR = 1.59 [1.35–1.88]), CCI ≥6 (RR = 1.55 [1.31–1.83]. Household income >$45 000 associated with lower risk for PCS (RR = 0.81 [0.70–0.93]), BP (RR = 0.80 [0.69–0.91]), and VT (RR = 0.86 [0.78–0.93]).

Conclusions

We operationalized physical resilience and identified factors predicting resilience after TKR. This approach may aid clinical risk stratification, guide further investigation of causes, and ultimately aid patients through the design of interventions to enhance physical resilience.
Persistence of the Immune Responses and Cross-Neutralizing Activity With Variants of Concern Following 2 Doses of Adjuvanted SCB-2019 Coronavirus Disease 2019 Vaccine
Authors: Richmond Peter C , Hatchuel Lara , Pacciarini Filippo , Hu Branda , Smolenov Igor , Li Ping , Liang Peng , Han Htay Htay , Liang Joshua , Clemens Ralf
Published: September 2021

Background

We have previously reported the safety and immunogenicity 4 weeks after 2 doses of the Clover coronavirus disease 2019 (COVID-19) vaccine candidate, SCB-2019, a stabilized prefusion form of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S-trimer). We now report persistence of antibodies up to 6 months after vaccination, and cross-neutralization titers against 3 variants of concern (VoCs).

Methods

In a phase 1 study, adult (18–54 years of age) and elderly (55–75 years of age) volunteers received 2 vaccinations 21 days apart with placebo or 3-, 9-, or 30-µg. We measured immunoglobulin G (IgG) antibodies against SCB-2019, angiotensin-converting enzyme 2 (ACE2) competitive binding antibodies, and neutralizing antibodies against wild-type SARS-CoV-2 (Wuhan-Hu-1) at days 101 and 184, and neutralizing antibodies against 3 VoCs, Alpha (B.1.1.7), Beta (B.1.351), and Gamma (P.1), in day 36 sera.

Results

Titers waned from their peak at days 36–50, but SCB-2019 IgG antibodies, ACE2 competitive binding antibodies, and neutralizing antibodies against wild-type SARS-CoV-2 persisted at 25%–35% of their observed peak levels at day 184. Day 36 sera also demonstrated dose-dependent increases in neutralizing titers against the 3 VoCs.

Conclusions

SCB-2019 dose-dependently induced immune responses against wild-type SARS-CoV-2, which persisted up to day 184. Neutralizing antibodies were cross-reactive against 3 of the most prevalent VoCs.
Genome size in cyclopoid copepods (Copepoda: Cyclopoida): chromatin diminution as a hypothesized mechanism of evolutionary constraint
Authors: Schutt Emilly , Hołyńska Maria , Wyngaard Grace A
Published: September 2021

Genome size is a fundamental property of organisms that impacts their molecular evolution and life histories. The hypothesis that somatic genome sizes in copepods in the order Cyclopoida are small and evolutionary constrained relative to those in the order Calanoida was proposed 15 years ago. Since then, the number of estimates has almost doubled and the taxon sampling has broadened. Here we add 14 new estimates from eight genera of freshwater cyclopoids that vary from 0.2 to 6.6 pg of DNA per nucleus in the soma; all except one are 2.0 pg DNA per nucleus or smaller. This new sample adds to the pattern of genome size in copepods and is remarkably similar to the distribution on which the original hypothesis was based, as well as those of subsequently published estimates. Embryonic chromatin diminution, during which large portions of DNA are excised from the presomatic cell lineage, is reported in Paracyclops affinis (G.O. Sars, 1863). This diminution results in a somatic genome that is one half the size of the germline genome. When the sizes of the germline genomes carried in presomatic cells of cyclopoid species that possess chromatin diminution are considered, the prediminuted germline genome sizes of cyclopoid embryos overlap with the distribution of calanoid somatic genome sizes, supporting the hypothesis that chromatin diminution has functioned as a mechanism to constrain somatic nuclear DNA content in cyclopoid copepods. Geographically based variation in genome size among populations is also reviewed.
Use of Functional Response Modeling to Evaluate the Effect of Temperature on Predation ofAmblyseius swirskii(Acari: Phytoseiidae) Adults Preying onTetranychus urticae(Acari: Tetranychidae) Nymphs
Authors: Farazmand Azadeh , Amir-Maafi Masood
Published: September 2021

In this research, functional responses of Amblyseius swirskii Athias-Henriot preying on different Tetranychus urticae Koch nymphal densities (2, 4, 8, 16, 32, 64, and 128) were studied at eight constant temperatures (15, 20, 25, 27.5, 30, 32.5, 35 and 37.5°C) in a circular Petri dish (3-cm diameter × 1-cm height) under lab conditions. At all temperatures, the logistic regression showed a type II functional response. A nonlinear relationship was found between temperature and attack rate and the reciprocal of handling time. The reciprocal of handling time decreased exponentially with increasing temperature. In contrast, the attack rate grew rapidly with increasing temperatures up to an optimum, showing a decreasing trend at higher temperatures. In order to quantify the functional response of A. swirskii over a broad range of temperatures and to gain a better estimation of attack rate and handling time, a temperature-settled functional response equation was suited to our data. Our model showed that the number of prey consumed increased with rising prey density. Also, the predation rates increased with increasing temperatures but decreased at extremely high temperatures. Based on our model, the predation rate begins at the lower temperature threshold (11.73°C) and reaches its peak at upper temperature threshold (29.43°C). The coefficient of determination (R2) of the random predator model was 0.99 for all temperatures. The capability of A. swirskii to search and consume T. urticae over a wide range of temperatures makes it a good agent for natural control of T. urticae in greenhouses.
Patient-Reported Functional Outcomes in Patients With Chronic Myeloid Leukemia After Stopping Tyrosine Kinase Inhibitors
Authors: Schoenbeck Kelly L , Atallah Ehab , Lin Li , Weinfurt Kevin P , Cortes Jorge , Deininger Michael W N , Kota Vamsi , Larson Richard A , Mauro Michael J , Oehler Vivian G , Pinilla-Ibarz Javier , Radich Jerald P , Schiffer Charles A , Shah Neil P , Silver Richard T , Thompson James E , Flynn Kathryn E
Published: September 2021

Treatment-free remission (TFR) is a goal for patients with chronic myeloid leukemia (CML). Functional outcomes after discontinuing tyrosine kinase inhibitor (TKI) treatment have not been described. Patient-Reported Outcomes Measurement Information System (PROMIS) measures of social, physical, cognitive, and sexual function were assessed over 36 months in 172 adult patients with chronic phase CML from 14 sites at baseline (on TKI) and after discontinuation. Linear mixed-effects models described the average trajectories for each patient-reported outcome measure after discontinuation and in those who restarted TKI. Of 112 patients in TFR at 12 months, 103 (92.0%) had a 3-point or greater improvement in social function, 80 (71.4%) in social isolation, 11 (9.8%) in satisfaction with sex life, 4 (3.6%) in physical function, and no patients had a 3-point or greater improvement in cognitive function or interest in sexual activity. Patients’ scores worsened after restarting TKI. This novel information on functional outcomes in TFR can help guide patient and clinician decision making.
Before Psychopharmacology
Authors: Shorter Edward
Published: September 2021

This chapter reviews cultures that used drugs to treat disorders of the mind, such as opium for melancholia in classical Greece. It cites Ida Macalpine and Richard Hunter, who commented that each age indulges in the conceit that nervous disorders are on the increase because of the complexity of its civilization with its discontents. It also recounts the seventeenth century, which had its sleepers and pills to purge melancholy, the eighteenth century, which used pacifick medicines, and the nineteenth century, which had composing pills and herbaceous tranquilizers. The chapter discusses the mid-nineteenth century, wherein biological thinking in psychiatry began to accelerate. It mentions Heinrich Laehr, who headed a provincial asylum in Halle in 1852 and stated that insanity is nothing else than a disease that only medical means may combat.
The Rise of Psychopharmacology
Authors: Shorter Edward
Published: September 2021

The First World Congress of Psychiatry in Paris in 1950 was a vast meeting that brought together everyone in the psychiatric world. The congress, which took place against a background of psychiatry as a mature clinical discipline in Europe, was considered the founding event in the history of psychopharmacology. In 1936, the American Board of Psychiatry and Neurology was established, wherein psychoanalytic doctrines penetrated the teaching of the entire discipline. This chapter emphasizes that there is no lineal connection between the early drugs and the discipline of psychopharmacology, while new drugs like chlorpromazine initiated the era of psychopharmacology. The chapter also explores the term “psychopharmacology,” which first surfaced in 1548 when Reinhard Lorich, a professor of theology in Marburg, used the term in the title of a collection of prayers for the dead.
Sally
Authors: Shorter Edward
Published: September 2021

Sally Laden helped turn the disease of depression into a gold mine. Laden was the world’s most influential female “psychopharmacologist,” and each of her creations began with an intonation about the terrible depression epidemic sweeping the globe. In psychiatry, the depression market had proven so huge that extending it to children would be desirable. Therefore, the pediatric exclusivity provision, which provided drug makers with 6 months of patent extension in exchange for conducting trials in the pediatric population, was welcomed by industry. Four major SSRI makers struggled to get into the pediatric depression market from 2000 to 2004. GlaxoSmithKline (GSK), which made the SSRI Paxil (paroxetine), conceived several trials in pediatric depression, and Sally Laden was assigned to write up one trial, #329.
Introduction
Authors: Lantos John D.
Published: September 2021

Shared decision making between doctors and patients has become the norm in medical decision making. There are three good reasons why there has been a shift from the traditional paternalistic model to a more bilateral and patient-centered model. First, the nature of medical knowledge has changed. Better understanding of the natural history of disease led to situations in which doctors had knowledge about their patients’ illnesses before the patients themselves had any symptoms of disease. In those situations, doctors need to disclose the diagnosis and the risks of forgoing treatment. Second, many modern therapies are initially worse than the diseases they treat. Again, explanations are necessary to convince the patient that the short-term risks and side effects are worth it to achieve the long-term benefits. Finally, there is often no single best treatment. Reasonable people can disagree about whether they’d trade off a slight increase in the chance of long-term survival for a worse quality of life. All of these changes create a health care environment in which both doctors and patients have more information than they have ever had before. That information makes decisions more complex. This chapter introduces the chapters in this book by which clinicians and philosophers try to clarify, critique, and understand the concept of shared decision making. In doing so, they use terms like “labyrinth,” “overwhelming,” “uncertainty,” and “dread.” Shared decision making as an ideal is inspiring and empowering but also frightening and somewhat ambiguous. This book tries to help doctors and patients navigate the complexities.
Fear, anxiety, and adjustment disorder in palliative care
Authors: Sherman Kerry A. , Kilby Christopher J.
Published: September 2021

Palliative care has major implications for the psychological well-being of not only the patient, but also family members and those close to them. Being offered palliative care can send a variety of signals to a patient, including a sense that the medical system has failed them and that their life is about to end, or maybe a sense of relief in knowing that their suffering will end soon. The family of the patient also experience a range of emotions associated with palliative care, often mimicking that of the patient. Although palliative care aims to minimize suffering and improve the quality of death for the patient, it is critical that the psychosocial well-being of the patient is addressed; neglect of these concerns will compromise the quality of palliative care, the quality of death, and overall psychological, emotional, and spiritual well-being of the patient, despite improvements in physical suffering. This chapter discusses the key importance of the need for reciprocal open communication and information provision during this difficult time between the patient, their family, and the palliative healthcare team. Ineffective communication can jeopardize the psychosocial well-being of the patient, with feelings of existential threat, isolation, depression, fear, anxiety, hopelessness, and wishing for a hastened death commonly reported. This chapter highlights these issues and provides an overview of evidence-based established approaches addressing the psychological well-being of both the patient and their family. An overarching theme across all intervention approaches is to maintain honest, open communication between medical staff, the patient, and their family.
Apathy
Authors: Lanctot Krista , Aleman André
Published: September 2021

Apathy is characterized by loss of motivation, decreased initiative, and emotional blunting. It is highly prevalent in neurological and psychiatric disorders such as Alzheimer’s disease, traumatic brain injury, schizophrenia, Parkinson’s disease, Huntington’s disease, cerebrovascular disorders, and mild behavioural impairment. It has negative outcomes including impairments in activities of daily living, caregiver burden, and higher rates of institutionalization and mortality. The definition of apathy has changed over the years alongside the development of diagnostic criteria and apathy scales and measurements. Apathy is emerging as a treatment target with interest in pharmacological, non-pharmacological, and neuromodulatory treatments for apathy. There is also an increased understanding of the neurobiology of apathy with functional and structural neuroimaging research studies. This book is a comprehensive, in-depth review from experts in neurology and psychiatry. It examines the current state of apathy in these various disorders while also summarizing apathy diagnostic criteria, scales and measurements, neuropathology, and treatments.
Tools, Time, Training, and Team—Military Primary Care Providers’ Perspectives on Improving Chronic Pain Assessment and Management
Authors: Mathew Asha , McQuinn Honor , Flynn Diane M , Ransom Jeffrey C , Doorenbos Ardith Z
Published: September 2021

Introduction

Primary care providers are on the front lines of chronic pain management, with many reporting frustration, low confidence, and dissatisfaction in handling the complex issues associated with chronic pain care. Given the importance of their role and reported inadequacies and dissatisfaction in managing this challenging population, it is important to understand the perspectives of primary care providers when considering approaches to chronic pain management. This qualitative descriptive study aimed to comprehensively summarize the provider challenges and suggestions to improve chronic pain care in military primary care settings.

Materials and Methods

Semi-structured interviews with 12 military primary care providers were conducted in a single U.S. Army medical center. All interviews were audio-recorded and lasted between 30 and 60 minutes. Interview transcripts were analyzed using ATLAS 9.0 software. Narratives were analyzed using a general inductive approach to content analysis. The Framework Method was used to organize the codes and emergent categories. All study procedures were approved by the Institutional Review Board of the University of Washington.

Results

Four categories captured providers’ challenges and suggestions for improving chronic pain care: (1) tools for comprehensive pain assessment and patient education, (2) time available for each chronic pain appointment, (3) provider training and education, and (4) team-based approach to chronic pain management. Providers suggested use of the Pain Assessment Screening Tool and Outcomes Registry, more time per visit, incorporation of chronic pain care in health sciences curriculum, consistent provider training across the board, insurance coverage for complementary and integrative therapies, patient education, and improved access to interdisciplinary chronic pain care.

Conclusions

Lack of standardized multifaceted tools, time constraints on chronic pain appointments, inadequate provider education, and limited access to complementary and integrative health therapies are significant provider challenges. Insurance coverage for complementary and integrative health therapies needs to be expanded. The Stepped Care Model of Pain Management is a positive and definite stride toward addressing many of these challenges. Future studies should examine the extent of improvement in guidelines-concordant chronic pain care, patient outcomes, and provider satisfaction following the implementation of the Stepped Care Model of Pain Management in military health settings.
Outcomes of Heated High Flow Nasal Cannula in Patients With Severe or Life-Threatening COVID-19 at a Military Treatment Facility—A Retrospective Cohort Study
Authors: Dollin Capt Yonatan P , Elliott Capt Brian P , Markert Ronald , Koroscil Maj Matthew T
Published: September 2021

Introduction

The coronavirus-19 (COVID-19) pandemic has forced radical changes in management of healthcare in military treatment facilities (MTFs). Military treatment facilities serve unique patients that have a service connection; thus, research and data on this population are relatively sparse. The purpose of this study was to provide descriptive data on characteristics and outcomes of MTF patients with COVID-19 who are treated with heated high-flow nasal cannula (HHFNC).

Materials and Methods

We performed a single-center retrospective cohort study at the Wright-Patterson Medical Center, a 52-bed hospital in an urban setting. We received approval from our Institutional Review Board. The cohort included patients admitted from June 1, 2020, through May 15, 2021 with severe or life-threatening COVID-19 from a positive severe acute respiratory syndrome–related coronavirus 2 reverse transcription polymerase chain reaction test who were placed on HHFNC during their hospital stay. Severe disease was defined as dyspnea, respiratory rate ≥30/min, blood oxygen saturation ≤93% without supplemental oxygen, partial pressure of arterial oxygen to fraction of inspired oxygen ratio <300, or lung infiltrates involving >50% of lung fields within 24-48 hours. Life-threatening disease was defined as having septic shock or multiple organ dysfunction or requiring intubation. Patients meeting these criteria were retrieved from a quality improvement cohort that represents a consecutive group of patients with COVID-19 admitted to the Wright-Patterson Medical Center.

Results

Our MTF managed 70 cases of severe or life-threatening COVID-19 from June 1, 2020, to May 15, 2021. Of the 70 cases, 19 (27%) were placed on HHFNC. After initiation of HHFNC, median SpO2/FiO2 was 281.8 and at 24 hours 145.4. Median respiratory rate oxygenation at these times were 10.7 and 9.4, respectively. Fifty percent required mechanical ventilation during hospitalization. Median intensive care unit length of stay was 11 days, with a maximum stay of 39 days. Median hospital length of stay was 12 days, with a maximum of 39 days.

Conclusion

Our retrospective cohort study characterized and analyzed outcomes observed in a MTF population, with severe or life-threatening COVID-19, who were treated with HHFNC. While the study did not have the power to make concrete conclusions on the optimal form of respiratory support for COVID-19 patients, our data support HHFNC as a reasonable treatment modality despite some notable differences between our cohort and prior studied patient populations.
Two Functional Epithelial Sodium Channel Isoforms Are Present in Rodents despite Pronounced Evolutionary Pseudogenization and Exon Fusion
Authors: Gettings Sean M , Maxeiner Stephan , Tzika Maria , Cobain Matthew R D , Ruf Irina , Benseler Fritz , Brose Nils , Krasteva-Christ Gabriela , Vande Velde Greetje , Schönberger Matthias , Althaus Mike
Published: September 2021

The epithelial sodium channel (ENaC) plays a key role in salt and water homeostasis in tetrapod vertebrates. There are four ENaC subunits (α, β, γ, δ), forming heterotrimeric αβγ- or δβγ-ENaCs. Although the physiology of αβγ-ENaC is well understood, for decades the field has stalled with respect to δβγ-ENaC due to the lack of mammalian model organisms. The SCNN1D gene coding for δ-ENaC was previously believed to be absent in rodents, hindering studies using standard laboratory animals. We analyzed all currently available rodent genomes and discovered that SCNN1D is present in rodents but was independently lost in five rodent lineages, including the Muridae (mice and rats). The independent loss of SCNN1D in rodent lineages may be constrained by phylogeny and taxon-specific adaptation to dry habitats, however habitat aridity does not provide a selection pressure for maintenance of SCNN1D across Rodentia. A fusion of two exons coding for a structurally flexible region in the extracellular domain of δ-ENaC appeared in the Hystricognathi (a group that includes guinea pigs). This conserved pattern evolved at least 41 Ma and represents a new autapomorphic feature for this clade. Exon fusion does not impair functionality of guinea pig (Cavia porcellus) δβγ-ENaC expressed in Xenopus oocytes. Electrophysiological characterization at the whole-cell and single-channel level revealed conserved biophysical features and mechanisms controlling guinea pig αβγ- and δβγ-ENaC function as compared with human orthologs. Guinea pigs therefore represent commercially available mammalian model animals that will help shed light on the physiological function of δ-ENaC.
Spontaneous rupture of the extensor pollicis longus tendon in systemic lupus erythematosus: A case report and literature review
Authors: Ikumi Akira , Okuwaki Shun , Hara Yuki , Yoshii Yuichi , Kawamura Haruo
Published: September 2021

Spontaneous tendon rupture is a rare entity. Herein, we report a case of spontaneous rupture of the extensor pollicis longus (EPL) tendon in a 61-year-old woman with systemic lupus erythematosus (SLE). The patient worked as an aesthetician and had a 42-year history of SLE that was well controlled using oral steroids. She presented with an inability to extend her left thumb, with no prior history of trauma or symptoms. On imaging, there was no evidence of degenerative changes or osteophyte formation in the gliding area of the EPL tendon. Intraoperatively, there was evidence of tendon rupture around Lister’s tubercle. We performed a tendon transfer of the extensor indicis proprius for repair. The patient recovered active thumb extension and returned to work 4 months after surgery without any complications. We suspected that spontaneous EPL tendon rupture was caused by a combination of disease-related factors, including long-term steroid use, chronic inflammation, and continuous mechanical stress from her work and daily activity. This case report demonstrates the multifactorial aetiology of spontaneous tendon rupture in patients with SLE and the importance of monitoring for this complication during routine follow-up.
Hypertrophic pachymeningitis in eosinophilic granulomatosis with polyangiitis
Authors: Izuka Shinji , Yamashita Hiroyuki , Takahashi Yuko , Kaneko Hiroshi
Published: September 2021

Eosinophilic granulomatosis with polyangiitis (EGPA) is one of the anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), which is characterised by systemic small vessels vasculitis with associated eosinophilia. Hypertrophic pachymeningitis (HP) is an inflammatory disease in which the cerebral or spinal dura mater is thickened. AAV other than EGPA may sometimes develop HP; however, patients with EGPA rarely develop HP. This is the case of myeloperoxidase-ANCA-positive EGPA that presented with headache and blurred vision and was diagnosed with HP. It was successfully treated with pulsed steroid therapy and intravenous cyclophosphamide without any relapse for more than 4 years.
Primary central nervous system lymphoma in a patient with neuropsychiatric systemic lupus erythematosus receiving mycophenolate mofetil: A case report and literature review
Authors: Sakairi Toru , Nakasatomi Masao , Watanabe Mitsuharu , Hamatani Hiroko , Ikeuchi Hidekazu , Kaneko Yoriaki , Handa Hiroshi , Hiromura Keiju
Published: September 2021

A 41-year-old woman with a 14-month history of systemic lupus erythematosus (SLE) presented with headache, aphasia, and agraphia. A laboratory examination revealed mild proteinuria, hypocomplementemia, and elevated anti-double-stranded DNA antibody levels. A cerebrospinal fluid analysis demonstrated elevated protein and interleukin-6 levels. Magnetic resonance imaging (MRI) of the brain identified multiple lesions suggestive of brain edemas and small haemorrhages. She was diagnosed as having neuropsychiatric lupus and lupus nephritis and received remission induction therapy with high-dose corticosteroid and intravenous cyclophosphamide. She achieved a complete remission, and treatment with mycophenolate mofetil (MMF) was initiated 3 months thereafter for remission maintenance. At 13 months after the exacerbation of SLE, she complained of headache and nausea. A gadolinium-enhanced MRI of the brain revealed a low-signal-intensity tumour with marginal ring enhancement of 50 mm in the left frontal lobe. The tumour was excised, and the histological diagnosis was diffuse large B-cell lymphoma with positive Epstein–Barr virus (EBV). MMF was discontinued. Remission induction therapy with rituximab, high-dose methotrexate, procarbazine, and vincristine was administered, and she achieved remission. Previous reports suggest that use of MMF is associated with primary central nervous system (CNS) lymphoma (PCNSL) in patients with lupus nephritis or other autoimmune diseases or in post-transplant patients. Our observation that PCNSL occurred after CNS involvement of SLE suggests that EBV and CNS inflammation arising from SLE might have contributed to the development of PCNSL.
Variations in the management of diffuse low-grade gliomas—A Scandinavian multicenter study
Authors: Munkvold Bodil Karoline Ravn , Solheim Ole , Bartek Jiri , Corell Alba , de Dios Eddie , Gulati Sasha , Helseth Eirik , Holmgren Klas , Jensdottir Margret , Lundborg Mina , Mireles Eduardo Erasmo Mendoza , Mahesparan Ruby , Tveiten Øystein Vesterli , Milos Peter , Redebrandt Henrietta Nittby , Pedersen Lars Kjelsberg , Ramm-Pettersen Jon , Sjöberg Rickard L , Sjögren Björn , Sjåvik Kristin , Smits Anja , Tomasevic Gregor , Vecchio Tomás Gómez , Vik-Mo Einar O , Zetterling Maria , Salvesen Øyvind , Jakola Asgeir S
Published: September 2021

Background

Early extensive surgery is a cornerstone in treatment of diffuse low-grade gliomas (DLGGs), and an additional survival benefit has been demonstrated from early radiochemotherapy in selected “high-risk” patients. Still, there are a number of controversies related to DLGG management. The objective of this multicenter population-based cohort study was to explore potential variations in diagnostic work-up and treatment between treating centers in 2 Scandinavian countries with similar public health care systems.

Methods

Patients screened for inclusion underwent primary surgery of a histopathologically verified diffuse WHO grade II glioma in the time period 2012 through 2017. Clinical and radiological data were collected from medical records and locally conducted research projects, whereupon differences between countries and inter-hospital variations were explored.

Results

A total of 642 patients were included (male:female ratio 1:4), and annual age-standardized incidence rates were 0.9 and 0.8 per 100 000 in Norway and Sweden, respectively. Considerable inter-hospital variations were observed in preoperative work-up, tumor diagnostics, surgical strategies, techniques for intraoperative guidance, as well as choice and timing of adjuvant therapy.

Conclusions

Despite geographical population-based case selection, similar health care organizations, and existing guidelines, there were considerable variations in DLGG management. While some can be attributed to differences in clinical implementation of current scientific knowledge, some of the observed inter-hospital variations reflect controversies related to diagnostics and treatment. Quantification of these disparities renders possible identification of treatment patterns associated with better or worse outcomes and may thus represent a step toward more uniform evidence-based care.
Rate of reinfections after SARS-CoV-2 primary infection in the population of an Italian province: a cohort study
Authors: Flacco M E , Acuti Martellucci C , Soldato G , Carota R , Fazii P , Caponetti A , Manzoli L
Published: September 2021

Background

Current data suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfections are rare, but no information are available on minors and after 12 months of follow-up.

Methods

This retrospective cohort study included all the population of an Italian Province, diagnosed with a SARS-CoV-2 infection from March 2020 to May 2021. The primary outcome was the incidence of a reinfection, defined as a new positive polymerase chain reaction (PCR) test occurring ≥90 days after complete resolution of the first infection, and data were retrieved from the official datasets (coronavirus disease 2019 [COVID-19], demographic, hospital and co-pay exemption) of the Local Health Unit (LHU) of Pescara.

Results

After an average of 201 days of follow-up (max. 414), we recorded 24 reinfections ≥90 days after the resolution of the first 7173 infections (0.33%). Four reinfections required hospitalization, one was lethal. Most of the reinfections (n = 13) occurred 6–9 months after the resolution of the first infection; no new infection was detected 12 or more months later and among the 832 minors.

Conclusions

This study confirms previous findings on a low risk of SARS-CoV-2 reinfection. If confirmed, these findings suggest that more targeted restriction policies can be applied to the subjects that recovered after a first infection.
Evening chronotype is associated with elevated biomarkers of cardiometabolic risk in the EpiHealth cohort: a cross-sectional study
Authors: Baldanzi Gabriel , Hammar Ulf , Fall Tove , Lindberg Eva , Lind Lars , Elmståhl Sölve , Theorell-Haglöw Jenny
Published: September 2021

Study Objectives

Individuals with evening chronotype have a higher risk of cardiovascular and metabolic disorders, although the underlying mechanisms are not well understood. In a population-based cohort, we aimed to investigate the association between chronotype and 242 circulating proteins from three panels of established or candidate biomarkers of cardiometabolic processes.

Methods

In 2,471 participants (49.7% men, mean age 61.2 ± 8.4 SD years) from the EpiHealth cohort, circulating proteins were analyzed with a multiplex proximity extension technique. Participants self-reported their chronotype on a five-level scale from extreme morning to extreme evening chronotype. With the intermediate chronotype set as the reference, each protein was added as the dependent variable in a series of linear regression models adjusted for confounders. Next, the chronotype coefficients were jointly tested and the resulting p-values adjusted for multiple testing using a false discovery rate (5%). For the associations identified, we then analyzed the marginal effect of each chronotype category.

Results

We identified 17 proteins associated with chronotype. Evening chronotype was positively associated with proteins previously linked to insulin resistance and cardiovascular risk, namely retinoic acid receptor protein 2, fatty acid-binding protein adipocyte, tissue-type plasminogen activator, and plasminogen activator inhibitor 1 (PAI-1). Additionally, PAI-1 was inversely associated with the extreme morning chronotype.

Conclusions

In this population-based study, proteins previously related to cardiometabolic risk were elevated in the evening chronotypes. These results may guide future research in the relation between chronotype and cardiometabolic disorders.
Rapid Detection of Red Rot Disease Pathogens (Pythium chondricola and P. porphyrae) in Pyropia yezoensis (Rhodophyta) with PCR-RFLP
Authors: Lee Soon Jeong , Lee Sang-Rae
Published: September 2021

Red rot disease is one of the best-known algal diseases infecting red algae Pyropia species. This disease decreases the quality and quantity of Pyropia aquaculture products in Korea, Japan, and China. Recently we found that Pythium chondricola (Oomycetes) infects blades of Pyropia yezoensis. Therefore, two Pythium species (P. chondricola and P. porphyrae) have been reported as red rot disease pathogens. In this study, we developed a species-specific molecular marker for distinguishing between the two red rot disease pathogens. Using a polymerase chain reaction restriction fragment length polymorphism method based on the mitochondrial cytochrome c oxidase subunit 2 (cox2) and nuclear ribosomal RNA large subunit regions, we classified these two Pythium species without a sequencing step. This new method had high specificity and efficiency for detecting red rot disease pathogens at the species level for both of the cultured and field samples. Therefore, the molecular markers developed in this study are effective for long-term monitoring of the infection and distribution pattern of each Pythium species in Pyropia aquaculture farms. Moreover, molecular monitoring can provide useful information for predicting infection and preventing mass mortality of Pyropia species by red rot disease.
Neurophysiologic Complexity in Children Increases with Developmental Age and Is Reduced by General Anesthesia
Authors: Puglia Michael P. , Li Duan , Leis Aleda M. , Jewell Elizabeth S. , Kaplan Chelsea M. , Therrian Megan , Kim Minkyung , Lee UnCheol , Mashour George A. , Vlisides Phillip E.
Published: September 2021

Background

Neurophysiologic complexity in the cortex has been shown to reflect changes in the level of consciousness in adults but remains incompletely understood in the developing brain. This study aimed to address changes in cortical complexity related to age and anesthetic state transitions. This study tested the hypotheses that cortical complexity would (1) increase with developmental age and (2) decrease during general anesthesia.

Methods

This was a single-center, prospective, cross-sectional study of healthy (American Society of Anesthesiologists physical status I or II) children (n = 50) of age 8 to 16 undergoing surgery with general anesthesia at Michigan Medicine. This age range was chosen because it reflects a period of substantial brain network maturation. Whole scalp (16-channel), wireless electroencephalographic data were collected from the preoperative period through the recovery of consciousness. Cortical complexity was measured using the Lempel–Ziv algorithm and analyzed during the baseline, premedication, maintenance of general anesthesia, and clinical recovery periods. The effect of spectral power on Lempel–Ziv complexity was analyzed by comparing the original complexity value with those of surrogate time series generated through phase randomization that preserves power spectrum.

Results

Baseline spatiotemporal Lempel–Ziv complexity increased with age (yr; slope [95% CI], 0.010 [0.004, 0.016]; P < 0.001); when normalized to account for spectral power, there was no significant age effect on cortical complexity (0.001 [–0.004, 0.005]; P = 0.737). General anesthesia was associated with a significant decrease in spatiotemporal complexity (median [25th, 75th]; baseline, 0.660 [0.620, 0.690] vs. maintenance, 0.459 [0.402, 0.527]; P < 0.001), and spatiotemporal complexity exceeded baseline levels during postoperative recovery (0.704 [0.642, 0.745]; P = 0.009). When normalized, there was a similar reduction in complexity during general anesthesia (baseline, 0.913 [0.887, 0.923] vs. maintenance 0.851 [0.823, 0.877]; P < 0.001), but complexity remained significantly reduced during recovery (0.873 [0.840, 0.902], P < 0.001).

Conclusions

Cortical complexity increased with developmental age and decreased during general anesthesia. This association remained significant when controlling for spectral changes during anesthetic-induced perturbations in consciousness but not with developmental age.

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A Surgeon’s Guide to Machine Learning
Authors: Lammers Daniel T. , Eckert Carly M. , Ahmad Muhammad A. , Bingham Jason R. , Eckert Matthew J.
Published: September 2021

Machine learning (ML) represents a collection of advanced data modeling techniques beyond the traditional statistical models and tests with which most clinicians are familiar. While a subset of artificial intelligence, ML is far from the science fiction impression frequently associated with AI. At its most basic, ML is about pattern finding, sometimes with complex algorithms. The advanced mathematical modeling of ML is seeing expanding use throughout healthcare and increasingly in the day-to-day practice of surgeons. As with any new technique or technology, a basic understanding of principles, applications, and limitations are essential for appropriate implementation. This primer is intended to provide the surgical reader an accelerated introduction to applied ML and considerations in potential research applications or the review of publications, including ML techniques.
Social Determinants of Health and Delirium Occurrence and Duration in Critically Ill Adults
Authors: Wu Ting-Ting , Zegers Marieke , Kooken Rens , Griffith John L. , Molnar Beth E. , Devlin John W. , van den Boogaard Mark
Published: September 2021

OBJECTIVES:

Social determinants of health may affect ICU outcome, but the association between social determinants of health and delirium remains unclear. We evaluated the association between three social determinants of health and delirium occurrence and duration in critically ill adults.

DESIGN:

Secondary, subgroup analysis of a cohort study.

SETTING:

Single, 36-bed mixed medical-surgical ICU in the Netherlands.

PATIENTS:

Nine hundred fifty-six adults consecutively admitted from July 2016 to February 2020. Patients admitted after elective surgery, residing in a nursing home, or not expected to survive greater than or equal to 48 hours were excluded.

INTERVENTION:

None.

MEASUREMENTS AND MAIN RESULTS:

Four factors related to three Center for Disease Control social determinants of health domains (social/community context [ethnicity], education access/quality [educational level], and economic stability [employment status and monthly income]) were collected at ICU admission from patients (or families). Well-trained ICU nurses evaluated patients without coma (Richmond Agitation Sedation Scale, –4, –5) and with the Confusion Assessment Method-ICU and/or a delirium day was defined by greater than or equal to 1 + Confusion Assessment Method-ICU and/or scheduled antipsychotic use. Multivariable logistic regression models controlling for ICU days and 10 delirium risk variables (before-ICU: age, Charlson, cognitive impairment, any antidepressant, antipsychotic, or benzodiazepine use; ICU baseline: Acute Physiology and Chronic Health Evaluation IV and admission type; daily ICU: Sequential Organ Failure Assessment, restraint use, coma, benzodiazepine, or opioid use) evaluated associations between each social determinant of health factor and both ICU delirium occurrence and duration. Delirium occurred in 393/956 patients (45.4%) for 2 days (1–5 d). Patients with low (vs high) income had more ICU delirium (p = 0.05). Multivariate analyses revealed no social determinants of health to be significantly associated with increased delirium occurrence or duration. Low (vs high) income was weakly associated with increased delirium occurrence (adjusted odds ratio, 1.83; 95% CI, 0.91–3.89). Low (vs high) education (adjusted relative risk, 1.21; 95% CI, 0.97–1.53) was weakly associated with a longer delirium duration.

CONCLUSIONS:

Social determinants of health did not affect ICU delirium in one Dutch region. Additional research across different countries/regions and where additional social determinants of health are considered is needed to define the association between social determinants of health and ICU delirium.