bluuebunny/crossref_metadata_2025 huggingface dataset:
Cellular immunity in subacute thyroiditis: a new perspective through neopterin
Authors: Sahin Tekin Melisa , Kocaturk Evin , Gurcu Sinem , Kayadibi Huseyin , Dibeklioglu Bilge , Yorulmaz Goknur
Published: May 2022

Subacute thyroiditis (SAT) is an inflammatory disorder of the thyroid gland. Although its etiology is not fully understood, it is believed to occur shortly after viral infections and is mostly associated with human leukocyte antigen (HLA)-B*35. Cellular immunity is prominent in SAT. Neopterin is produced by activated monocytes/macrophages and is a marker of cellular immunity. Its production is stimulated by interferon gamma (IFN-γ), provided mainly by activated helper T lymphocytes type 1 (Th1) in the adaptive immune system. Therefore, with these cells’ activation, an increase in serum neopterin levels is expected. We aimed to evaluate neopterin levels in demonstrating cellular immunity in SAT and compared 15 SAT patients with 16 healthy controls. Since all SAT patients were in the active thyrotoxic phase, we found a significant difference in thyroid functions. Classical inflammatory markers, erythrocyte sedimentation rate, and C-reactive protein were markedly elevated in the patient group. Although we expected to find an increase considering that cellular immunity is at the forefront in the pathogenesis of SAT, we found serum neopterin levels significantly lower in the patient group than in the control group. There is an increase in CD8+ T cells in the thyroid tissue in SAT. The possible relationship with HLA-B*35- major histocompatibility complex class I in SAT, and the antigen presentation to CD8+ T cells may be the reason why we observed low serum neopterin levels in patients due to the cytokine imbalance. Neopterin provides unique and independent data from classical acute phase response indicators.
Increased levels of pathogenic Th17 cells and diminished function of CD69+ Treg lymphocytes in patients with overweight
Authors: Mendoza-Pérez Alejandra , Vitales-Noyola Marlen , González-Baranda Larisa , Álvarez-Quiroga Crisol , Hernández-Castro Berenice , Monsiváis-Urenda Adriana , Baranda Lourdes , Niño-Moreno Perla , Hurtado Gilberto , Sánchez-Gutiérrez Raquel , González-Amaro Roberto
Published: May 2022

A low-grade inflammatory phenomenon is a feature of overweight and metabolic syndrome. The involvement of a pro-inflammatory Th17 lymphocyte subset and the CD69+ T regulatory (Treg) cell subtype in patients with metabolic dysfunction associated with or without overweight has not been fully elucidated. The aim of this study was to perform a quantitative and functional analysis of pathogenic Th17 lymphocytes and CD69+ Treg cells in patients with metabolic dysfunction (insulin resistance and dyslipidemia). The number of pathogenic Th17 cells and the levels and function of CD69+ Treg cells were analyzed in blood samples from individuals with metabolic dysfunction, associated with or without overweight. Pathogenic and non-pathogenic Th17 lymphocytes as well as Th22 cells were determined by eight-color flow cytometry analysis, whereas the levels and suppressive function of CD69+ Treg cells were also analyzed by multiparametric flow cytometry. We detected increased levels of pro-inflammatory Th17 pathogenic cells and Th22 lymphocytes in overweight unhealthy individuals (P < 0.001, compared to normal weight healthy). Conversely, diminished numbers of CD69+ Treg lymphocytes were observed in metabolically unhealthy individuals, with or without overweight. Likewise, the immunosuppressive function of CD69+ Treg cells was also defective in these patients. The increased levels of pathogenic Th17 cells along with a diminished number and function of CD69+ Treg lymphocytes may significantly contribute to the low-grade inflammatory phenomenon of metabolically unhealthy patients.
Egg rejection based on egg size recognition as a specific strategy against parasitic cuckoos
Authors: Ye Ping , Cai Yan , Wu Neng , Yao Xiaogang , Li Guangrong , Liang Wei , Yang Canchao
Published: May 2022

In the coevolutionary interactions between avian brood parasites and their hosts, egg recognition based on color and/or pattern is a common and effective defense to counter parasitism. However, for egg recognition based on size, only a few studies have found affirmative results, and they do not provide unambiguous evidence that egg size recognition in hosts has evolved as an important and specific anti-parasite adaptation against parasite eggs. We studied the brood parasite system between the Asian emerald cuckoo Chrysococcyx maculatus and its host, the chestnut-crowned warbler Phylloscopus castaniceps. The cuckoo parasitizes the warbler using non-mimetic and larger eggs at a parasitism rate of 12.9%. The warbler nests used in this experiment were built in a dark environment with the nest illuminance near 0 lux. Experiments with 2 types of model eggs with colors and patterns resembling cuckoo eggs of different sizes (cuckoo egg size or host egg size) showed that the warblers were able to reject 63.6% of cuckoo model eggs under these dim light conditions. However, model eggs with the same color and pattern similar to the warbler egg size were always accepted. This study provides strong evidence supporting the theory that egg size recognition can be evolved in hosts as a specific anti-parasite adaptation against cuckoos. We suggest that the egg size recognition of the warbler is an outcome of the tradeoff between the costs of violating the parental investment rule and suffering cuckoo parasitism.
Efficient screening for severe aortic valve stenosis using understandable artificial intelligence: a prospective diagnostic accuracy study
Authors: Makimoto Hisaki , Shiraga Takeru , Kohlmann Benita , Magnisali Christofori Eleni , Gerguri Shqipe , Motoyama Nobuaki , Clasen Lukas , Bejinariu Alexandru , Klein Kathrin , Makimoto Asuka , Jung Christian , Westenfeld Ralf , Zeus Tobias , Kelm Malte
Published: May 2022

Aims

The medical need for screening of aortic valve stenosis (AS), which leads to timely and appropriate medical intervention, is rapidly increasing because of the high prevalence of AS in elderly population. This study aimed to establish a screening method using understandable artificial intelligence (AI) to detect severe AS based on heart sounds and to package the built AI into a smartphone application.

Methods and results

In this diagnostic accuracy study, we developed multiple convolutional neural networks (CNNs) using a modified stratified five-fold cross-validation to detect severe AS in electronic heart sound data recorded at three auscultation locations. Clinical validation was performed with the developed smartphone application in an independent cohort (model establishment: n = 556, clinical validation: n = 132). Our ensemble technique integrating the heart sounds from multiple auscultation locations increased the detection accuracy of CNN model by compensating detection errors. The established smartphone application achieved a sensitivity, specificity, accuracy, and F1 value of 97.6% (41/42), 94.4% (85/90), 95.7% (126/132), and 0.93, respectively, which were higher compared with the consensus of cardiologists (81.0%, 93.3%, 89.4%, and 0.829, respectively), implying a good utility for severe AS screening. The Gradient-based Class Activation Map demonstrated that the built AIs could focus on specific heart sounds to differentiate the severity of AS.

Conclusions

Our CNN model combining multiple auscultation locations and exported on smartphone application could efficiently identify severe AS based on heart sounds. The visual explanation of AI decisions for heart sounds was interpretable. These technologies may support medical training and remote consultations.
Surgical reconstruction of a giant left ventricular aneurysm with prior unloading using a microaxial pump
Authors: Medina Estrada Marta L , Silaschi Miriam C , Charitos Efstratios I , Treede Hendrik
Published: May 2022

A 46-year-old male patient presented with cardiac decompensation due to a giant left ventricular aneurysm combined with a severely reduced left ventricular function after a silent myocardial infarction. Left ventricular unloading was performed with a microaxial pump as a bridge to surgery. Myocardial function in the basal segments was preserved and surgical ventricular reconstruction was performed successfully.
Outline of Treatment Procedures and Basic Principles Underlying Treatment
Authors: Craske Michelle G. , Barlow David H.
Published: May 2022

This chapter outlines the treatment procedures and looks at the basic principles underlying treatment. There are four main sections to the Mastery of Your Anxiety and Panic: Workbook, Fifth Edition (MAP–5): Basics, Coping Skills, Exposure to Feared Symptoms and Situations, and Planning for the Future. The treatment begins with education about the nature of panic disorder, the causes of panic and anxiety, and the ways panic and anxiety are perpetuated by feedback loops among physical, cognitive, and behavioral response systems. The important coping skills include breathing retraining and cognitive restructuring. The chapter then considers the multiple mechanisms for therapeutic change during exposure therapy: self-efficacy and control; emotional processing; extinction; and violation of expectancies and fear toleration. Ultimately, the skills developed through this program are intended to serve clients far beyond its completion; they are skills clients can rely on for the rest of their lives, or for however long symptoms of panic and/or agoraphobia persist.
Learning to Record Panic and Anxiety
Authors: Craske Michelle G. , Barlow David H.
Published: May 2022

This chapter highlights the importance of objective recordkeeping of panic and anxiety. Keeping records offsets the anxiety-inducing effects of avoidance, subjective monitoring, and recall biases. The goal is for clients to begin to become observers rather than victims of their anxiety. The chapter then looks at the two forms of recording panic and anxiety: Your Panic Attack Record and Your Daily Mood Record. The therapist will provide corrective feedback and answer questions as the client completes (in session) a Your Panic Attack Record for a recent panic attack. Therapists should aid clients in recording their thoughts and behaviors by helping them to consider what it was they were most worried about happening in the panic attack, and what they did as a result. In addition, therapists should provide feedback to clients as they complete the ratings on the Your Daily Mood Record for today and yesterday.
Breathing Skills
Authors: Barlow David H. , Craske Michelle G.
Published: May 2022

This chapter focuses on the importance of understanding how breathing patterns contribute to panic and anxiety. Many people overbreathe/hyperventilate when they panic—in other words, they breathe too quickly. Technically, to overbreathe or to hyperventilate means to breathe in more oxygen than is needed by the body. The chapter then explains the mechanics of breathing and the symptoms of overbreathing, which will help correct the mistaken belief that the symptoms of overbreathing are harmful. It also looks at the process of learning diaphragmatic breathing and slow breathing. Finally, the chapter provides a guide on how to apply breathing skills as a coping skill.
Facing Agoraphobia Situations
Authors: Barlow David H. , Craske Michelle G.
Published: May 2022

This chapter explores the value of facing agoraphobia situations. In many ways, direct experience is the most powerful way of learning. It is essential that one eventually repeatedly face and deal with all the situations on one’s agoraphobia hierarchy. Sometimes people believe that they have already tried to face agoraphobia situations, without any success. As a result, they mistakenly judge that this treatment approach does not work. However, it is likely that previous unsuccessful attempts at facing the fear were not structured in exactly the right way. The chapter then presents the most effective method of exposure exercises. The practices with agoraphobia situations are intended to do three things: gather new information to help one fully realize that what one is worried about happening is very unlikely to happen or never happens; let one learn that one can handle and survive the feelings of anxiety and fear; and show that one can accomplish the things that one has been avoiding.
Involving Others
Authors: Barlow David H. , Craske Michelle G.
Published: May 2022

This chapter presents ways for incorporating significant others to help one confront one’s fears of agoraphobia situations. Research suggests that involving spouses, life partners, family, or friends in the therapy process can lead to continued improvement, especially after formal therapy is over. Helpers can learn about panic and agoraphobia by reading this workbook, by having a mental health professional explain things to them, or by asking the client to explain things to them in as objective a way as possible. The helper may aid the client by discussing the task before the client attempts it and after it is over, prompting the client to use their thinking skills and breathing, and helping them to evaluate their accomplishments objectively. Also, the helper can join the client as they complete their exposure practice. However, it is important to remember that if the helper or partner accompanies the client, they could become a safety signal. Therefore, it is essential that, eventually, the client is able to face the symptoms or situation on their own, without their helper.
The Nature of Panic Disorder and Agoraphobia
Authors: Craske Michelle G. , Barlow David H. , Woodard Lauren S.
Published: May 2022

This chapter provides an overview of the nature of panic disorder and agoraphobia. The key features of panic disorder are (1) one or more episodes of abrupt, intense fear or discomfort (i.e., a panic attack) and (2) persistent anxiety or worry about the recurrence of panic attacks, their consequences, or life changes as a result of the attacks. Individuals with panic disorder often avoid, feel hesitant about, or feel nervous in situations where they expect panic attacks or other physical symptoms to occur. Typically, these situations are ones where one may not be able to escape or find help. Avoiding situations from which escape might be difficult or where help may be unavailable in the event of a panic attack or other physical symptoms is called agoraphobia. The chapter then outlines the typical agoraphobia situations. The kind of treatment that is described in this program is called cognitive behavioral therapy (CBT) and it is designed to educate and to teach constructive ways of coping.
Learning More Breathing and Thinking Skills
Authors: Craske Michelle G. , Barlow David H. , Woodard Lauren S.
Published: May 2022

This chapter examines the importance of developing more breathing skills and thinking skills, looking at ways of replacing negative thoughts with evidence-based thinking. Two errors characterize anxious thinking: (1) jumping to conclusions and (2) blowing things out of proportion. The first step toward change is to treat thoughts as guesses rather than as facts. The goal is to develop more realistic ways of thinking. One can develop more realistic beliefs by considering all of the evidence—and from obtaining additional information, where necessary—such as the information on panic attacks. It is important to recognize that whatever it is that one is worried about is not going to last forever and is survivable.
Planning for the Future
Authors: Craske Michelle G. , Barlow David H. , Woodard Lauren S.
Published: May 2022

This chapter covers the process of learning how to structure continued practice, ways of maintaining progress, and how to approach high-risk times and manage setbacks. One can use the Your Practice Plan form to list all of the things to be practiced over the next few weeks in terms of breathing skills, thinking skills, facing agoraphobia situations, and facing symptoms. The chapter then looks at several ways to maintain the progress that one has made so far. It is helpful to anticipate the kinds of stressful events one may experience ahead of time and to prepare for them in a matter-of-fact way. A panic attack or resurgence of anxiety does not mean that one is getting worse or that one has lost all of the progress that one has gained. The most important thing to do when one has a flare-up of anxious symptoms is to repeat everything one has already done.
Physical conditions and chemical abundances of the variable planetary nebula IC 4997
Authors: Danehkar A , Parthasarathy M
Published: May 2022

The planetary nebula (PN) IC 4997 is one of a few rapidly evolving objects with variable brightness and nebular emission around a hydrogen-deficient star. In this study, we have determined the physical conditions and chemical abundances of this object using the collisionally excited lines (CELs) and optical recombination lines (ORLs) measured from the medium-resolution spectra taken in 2014 July with the FIbre-fed Échelle Spectrograph on the Nordic Optical Telescope at La Palma Observatory. We derived electron densities of ≳ 3 × 104 cm−3 and electron temperatures of ≳ 14 000 K from CELs, whereas cooler temperatures of ∼11 000 and ∼7000 K were obtained from helium and heavy element ORLs, respectively. The elemental abundances deduced from CELs point to a metal-poor progenitor with [O/H] ≲ −0.75, whereas the ORL abundances are slightly above the solar metallicity, [O/H] ≈ 0.15. Our abundance analysis indicates that the abundance discrepancy factors (ADFs ≡ ORLs/CELs) of this PN are relatively large: ADF(O2+) ≳ 8 and ADF(N2+) ≳ 7. Further research is needed to find out how the ADFs and variable emissions are formed in this object and whether they are associated with a binary companion or a very late thermal pulse.
A unified serum IgG4 cut-off level for the diagnosis of IgG4-related disease using a wide array of kits
Authors: Yan Songxin , Peng Yu , Cheng Linlin , Li Haolong , Zhan Haoting , Zhang Xinyao , Li Zepeng , Zhang Wen , Li Yongzhe
Published: May 2022

Objectives

An immunoglobulin G4 (IgG4) level above 1350 mg/L is one of the comprehensive criteria for the diagnosis of IgG4-related disease (IgG4-RD). The purpose of this study was to evaluate the differences in IgG4 levels determined using reagents from two main manufacturers and their concordance with clinical diagnosis.

Methods

IgG4 levels were measured in 309 patients, including 146, 40, 42, 41, and 40 patients with untreated IgG4-RD, pancreatic cancer, primary Sjogren syndrome, systemic lupus erythematosus, and idiopathic retroperitoneal fibrosis, respectively, and 141 healthy controls. The results obtained using the Binding Site and Siemens reagents were compared in patients with IgG4-RD.

Results

The serum IgG4 level measured using the Siemens reagent was almost two times that measured using the Binding Site reagent. The rate of IgG4-negative patients, which was 19.9% based on measurement using the Binding Site reagent, was only 4.8% based on measurement using the Siemens reagent (p < .001).

Conclusions

There were significant differences in serum IgG4 levels based on commonly used reagents from different manufacturers. The IgG4 cut-off level of 1350 mg/L was not suitable for all detection reagents. Clinicians and patients should be cognizant of these differences associated with the specific detection reagents when evaluating the test results.
The First Case of Usutu Virus Neuroinvasive Disease in Austria, 2021
Authors: Graninger Marianne , Hubmer Stefan , Riederer Franz , Kettner Stephan , Hauk Martin , Auf Tasnim , Aberle Judith H , Stiasny Karin , Aberle Stephan W , Camp Jeremy V
Published: May 2022

Usutu virus (USUV) is a mosquito-borne flavivirus closely related to West Nile virus (WNV) that is endemic in many European countries. We report the first case of USUV neuroinvasive disease in Austria and discuss challenges in differentiating USUV from WNV infections in areas where both viruses are endemic.
Plasticity in structure and assembly of SARS-CoV-2 nucleocapsid protein
Authors: Zhao Huaying , Nguyen Ai , Wu Di , Li Yan , Hassan Sergio A , Chen Jiji , Shroff Hari , Piszczek Grzegorz , Schuck Peter
Published: May 2022

Worldwide SARS-CoV-2 sequencing efforts track emerging mutations in its spike protein, as well as characteristic mutations in other viral proteins. Besides their epidemiological importance, the observed SARS-CoV-2 sequences present an ensemble of viable protein variants, and thereby a source of information on viral protein structure and function. Charting the mutational landscape of the nucleocapsid (N) protein that facilitates viral assembly, we observe variability exceeding that of the spike protein, with more than 86% of residues that can be substituted, on average by three to four different amino acids. However, mutations exhibit an uneven distribution that tracks known structural features but also reveals highly protected stretches of unknown function. One of these conserved regions is in the central disordered linker proximal to the N-G215C mutation that has become dominant in the Delta variant, outcompeting G215 variants without further spike or N-protein substitutions. Structural models suggest that the G215C mutation stabilizes conserved transient helices in the disordered linker serving as protein–protein interaction interfaces. Comparing Delta variant N-protein to its ancestral version in biophysical experiments, we find a significantly more compact and less disordered structure. N-G215C exhibits substantially stronger self-association, shifting the unliganded protein from a dimeric to a tetrameric oligomeric state, which leads to enhanced coassembly with nucleic acids. This suggests that the sequence variability of N-protein is mirrored by high plasticity of N-protein biophysical properties, which we hypothesize can be exploited by SARS-CoV-2 to achieve greater efficiency of viral assembly, and thereby enhanced infectivity.
Statistical electromagnetics for industrial pharmaceutical lyophilization
Authors: Abdelraheem Ahmed , Tukra Rishabh , Kazarin Petr , Sinanis Michael D , Topp Elizabeth M , Alexeenko Alina , Peroulis Dimitrios
Published: May 2022

Lyophilization is a common unit operation in pharmaceutical manufacturing but is a prolonged vacuum drying process with poor energy utilization. Microwave-assisted vacuum drying has been investigated to accelerate the lyophilization process. However, the literature lacks methodical approaches that consider the lyophilizer, the lyophilizate, the microwave power uniformity, the resulting heat uniformity, and the scalability. We present a microwave–vacuum drying method based on the statistical electromagnetics theory. The method offers an optimum frequency selection procedure that accounts for the lyophilizer and the lyophilizate. The 2.45 GHz frequency conventionally utilized is proven to be far from optimum. The method is applied in a microwave-assisted heating configuration to pharmaceutical excipients (sucrose and mannitol) and different myoglobin formulations in a lab-scale lyophilizer. At 18 GHz frequency and 60 W microwave power, the method shows nearly three times speed-up in the primary drying stage of sucrose relative to the conventional lyophilization cycle for typical laboratory batches. The uniformity of the microwave power inside the chamber is controlled within ± 1 dB. The resulting heating uniformity measured through residual moisture analysis shows 12.7% of normalized SD of moisture level across the batch in a microwave-assisted cycle as opposed to 15.3% in the conventional cycle. Conventional and microwave lyophilized formulations are characterized using solid-state hydrogen-deuterium exchange-mass spectrometry (ssHDX-MS), solid-state Fourier transform infrared spectroscopy (ssFTIR), circular dichroism (CD), and accelerated stability testing (AST). Characterization shows comparable protein structure and stability. Heat and mass transfer simulations quantify further effects of optimal volumetric heating via the high-frequency statistical microwave heating.
The education Sustainable Development Goal and the generative power of failing metrics
Authors: Grek Sotiria
Published: May 2022

The article traces the development of the epistemic infrastructure of the education sustainable development goal (SDG) in order to examine the ways that the incremental buildup of the discourse, technical expertise, and necessary—although always fragile—alliances facilitated a paradigmatic policy shift in the field of education: This is the move from the measurement of schooling to the measurement of learning. Through an analytical lens that examines the entanglement of the material, semiotic, and political and temporal/spatial elements of the infrastructure, the article shows how the sustainable development goal 4 (SDG4) as an epistemic infrastructure enabled a fundamental reorientation in the field of global education governance. The article discusses the ways that quantification, despite—and often thanks to—its failings, folded contested discourses, decision-making, politics, and ideas into its processes. Thus, the paper argues that the making of the SDG4 represents a paradigmatic policy shift; one that is not only to be traced in the move from schooling to the policy prioritization of learning outcomes but also in the very production of global public policy through the work of the SDGs as epistemic infrastructures.
Dysmaturational Longitudinal Epigenetic Aging During Transition to Psychosis
Authors: Iftimovici Anton , Kebir Oussama , Jiao Chuan , He Qin , Krebs Marie-Odile , Chaumette Boris
Published: May 2022

Psychosis frequently occurs during adolescence and young adulthood, possibly as a result of gene-environment interactions, mediated by epigenetic mechanisms such as DNA methylation. Methylation patterns can be leveraged to predict epigenetic age in order to identify anomalies in aging trajectories that may be associated with the emergence of psychosis. Thus, epigenetic age may provide a measurable surrogate of psychotic risk or psychosis’ emergence, and shed light on the neurodevelopmental model of psychosis. In this study, we present the first longitudinal analysis of epigenetic age trajectory during conversion to psychosis in a population at ultra-high-risk, with available genome-wide methylation DNA at two time points, at baseline and after one year of follow-up (N = 38 × 2). After predicting epigenetic age, we computed epigenetic age gap as the cross-sectional difference between real age and predicted age, and (longitudinal) epigenetic age acceleration as the derivative of predicted age with respect to time. At baseline, future converters were 2.7 years younger than nonconverters and this difference disappeared at follow-up, when some converted to psychosis. This is because during conversion to psychosis, the epigenetic age of converters accelerated by 2.8 years/year compared to nonconverters. This acceleration was robust with a strictly positive 95% confidence interval, and held its significance after adjustment for age, sex, and cannabis intake. The methylation sites most associated with aging were on genes also linked with schizophrenia and neurodevelopmental disorders. This accelerated age trajectory, following a previous deceleration, may therefore reflect dysmaturational processes.
Sleeping in a bubble: factors affecting sleep during New Zealand’s COVID-19 lockdown
Authors: Gibson Rosemary , Shetty Harshi , Carter Mikaela , Münch Mirjam
Published: May 2022

New Zealand (NZ) enforced a rigorous lockdown in response to the outbreak of COVID-19 in 2020. Infection rates remained remarkably low, yet social and personal routines were affected. Factors associated with reporting worsening sleep were explored using an anonymous online survey launched during New Zealand’s 2020 lockdown. Participants were 723 adults aged 20–85 years (median: 45 years, 82% women). Bed and wake times occurred significantly later compared to pre-lockdown estimates and resulted in shorter social jetlag (15 min). During lockdown, 54.5% were identified as “poor sleepers” [i.e. score > 5 on the Pittsburgh Sleep Quality Index (PSQI)]. Overall, 45% rated their sleep quality to worsen compared to pre-lockdown, 22% reported an improvement. Reports of worsening sleep were significantly related to increased sleep latency, reduced sleep efficiency, and heightened PSQI scores compared to those with better sleep or no change. Subjectively worse sleep was significantly associated with less time engaging in physical activity, less exposure to daylight, and social interactions compared to pre-lockdown estimates (p < .05). Logistic regression models identified significant relationships between having more vivid dreams and worsening sleep. Worse sleepers also had increased likelihoods of reporting poorer mood and they also scored higher for anxiety compared to those with no change or improved sleep during lockdown (p < .05). Pandemic-related restrictions contributed to poorer self-reported sleep which was linked to deterioration of mood. Negative affect was comparatively lower than reported elsewhere. These findings provide unique insights to the psychosocial impact of the initial COVID-19 lockdown in New Zealand, where the disease outbreak remained low.
Time Trends in Unilateral and Bilateral Oophorectomy in a Geographically Defined American Population
Authors: Erickson Zachary , Rocca Walter A. , Smith Carin Y. , Gazzuola Rocca Liliana , Stewart Elizabeth A. , Laughlin-Tommaso Shannon K. , Mielke Michelle M.
Published: May 2022

OBJECTIVE:

To evaluate trends in the incidence of premenopausal unilateral and bilateral oophorectomy between 1950 and 2018.

METHODS:

The Rochester Epidemiology Project medical records–linkage system was used to identify all women aged 18–49 years who were residents of Olmsted County, Minnesota, and underwent unilateral or bilateral oophorectomy before spontaneous menopause between January 1, 1950, and December 31, 2018. Population denominators were derived from the U.S. Decennial Censuses for the years 1950–2010, and intercensal year population denominators were linearly interpolated. For 2011–2018, the annual population denominators were obtained from the U.S. Census projections. Where appropriate, overall incidence rates were age-adjusted to the total U.S. female population from the 2010 Census.

RESULTS:

There were 5,154 oophorectomies in Olmsted County across the 69-year period between 1950 and 2018, and 2.9% showed malignant disease on pathology. A total of 2,092 (40.6%) women underwent unilateral oophorectomy, and 3,062 (59.4%) women underwent bilateral oophorectomy. More than half (n=1,750, 57.2%) of the bilateral oophorectomies occurred between 1990 and 2009. Until 1975–1979, the incidence of unilateral oophorectomy was mostly higher than bilateral oophorectomy. From 1980–1984 until 2000–2004, the incidence of bilateral oophorectomy more than doubled and the incidence of unilateral oophorectomy declined. After 2005, both procedures declined and converged to a similar incidence in 2015–2018. The decline in premenopausal bilateral oophorectomy over the past 14 years (2005–2018) was most pronounced for women who underwent oophorectomy concurrently with hysterectomy or did not have any ovarian indication.

CONCLUSION:

The incidence rates of unilateral and bilateral oophorectomy have varied greatly across the 69-year period of this study. In the past 14 years, the incidence of premenopausal unilateral and bilateral oophorectomy has decreased. These trends reflect the effects of the initial 2005–2006 publications and the subsequent expanding body of evidence against the practice of oophorectomy for noncancer indications.
Early Discontinuation, Results Reporting, and Publication of Gynecology Clinical Trials From 2007 to 2020
Authors: Steinberg Jecca R. , Magnani Christopher J. , Turner Brandon E. , Weeks Brannon T. , Young Anna Marie P. , Lu Connie Fei , Zhang Naixin , Richardson Michael Taylor , Fitzgerald Alison Conway , Mekonnen Zesemayat , Redman Tene , Adetunji Modupe , Martin Shanique A. , Anderson Jill N. , Chan Katelyn S. , Milad Magdy P.
Published: May 2022

OBJECTIVE:

To characterize gynecology clinical trials over time, compare gynecology subspecialties, and analyze factors associated with early discontinuation, results reporting, and publication.

METHODS:

We conducted a cross-sectional analysis of all gynecology trials registered on ClinicalTrials.gov between 2007 and 2020 and their resulting publications. Trials were analyzed with descriptive, multivariable logistic, and Cox regression analyses. Primary exposure variables were trial funding and subspecialty. The three primary outcomes included early discontinuation, results reporting to ClinicalTrials.gov, and publication in a peer-reviewed journal indexed on PubMed.

RESULTS:

Of 223,690 trials registered on ClinicalTrials.gov between October 2007 and March 2020, only 3.7% focused on gynecology (n=8,174, approximately 3,759,086 participants). Subspecialties included reproductive endocrinology and infertility (n=1,428, 17.5%), gynecologic oncology (n=2,063, 25.2%), urogynecology (n=1,118, 13.7%), family planning (n=648, 7.9%), and other benign gynecology (n=2,917, 35.7%). Only 42.0% of completed trials disseminated results through results reporting and publication. Of all funding types, industry-funded trials were the most likely to be discontinued early (P<.001). Academic-funded trials were the least likely to report results (adjusted odds ratio [aOR] 0.38, 95% CI 0.30–0.50) but the most likely to publish (aOR 1.62, 95% CI 1.24–2.12). The number of reproductive endocrinology and infertility trials increased the most of any subspecialty between 2007 and 2020 (6.4% growth rate). Reproductive endocrinology and infertility and family planning trials were the most likely to be stopped early (reproductive endocrinology and infertility: adjusted hazard ratio [aHR] 2.08, 95% CI 1.59–2.71; family planning: aHR 1.55 95% CI 1.06–2.25). When completed, reproductive endocrinology and infertility trials were the least likely to report results (aOR 0.58, 95% CI 0.38–0.88). No significant differences were seen between subspecialties with respect to publication.

CONCLUSION:

Gynecology trials comprise only 3.7% of all clinical trials. The paucity of gynecology clinical trials aligns with decades of female underrepresentation in research. When completed, gynecology trials have poor dissemination. Our findings raise concern about bias in the performance, reporting, and publication of gynecology clinical trials.
Development and Validation of a Model to Predict Postdischarge Opioid Use After Cesarean Birth
Authors: Osmundson Sarah S. , Halvorson Alese , Graves Kristin N. , Wang Clara , Bruehl Stephen , Grijalva Carlos G. , France Dan , Hartmann Katherine , Mokshagundam Shilpa , Harrell Frank E.
Published: May 2022

OBJECTIVE:

To develop and validate a prediction model for postdischarge opioid use in patients undergoing cesarean birth.

METHODS:

We conducted a prospective cohort study of patients undergoing cesarean birth. Patients were enrolled postoperatively, and they completed pain and opioid use questionnaires 14 days after cesarean birth. Clinical data were abstracted from the electronic health record (EHR). Participants were prescribed 30 tablets of hydrocodone 5 mg–acetaminophen 325 mg at discharge and were queried about postdischarge opioid use. The primary outcome was total morphine milligram equivalents used. We constructed three proportional odds predictive models of postdischarge opioid use: a full model with 34 predictors available before hospital discharge, an EHR model that excluded questionnaire data, and a reduced model. The reduced model used forward selection to sequentially add predictors until 90% of the full model performance was achieved. Predictors were ranked a priori based on data from the literature and prior research. Predictive accuracy was estimated using discrimination (concordance index).

RESULTS:

Between 2019 and 2020, 459 participants were enrolled and 279 filled the standardized study prescription. Of the 398 with outcome measurements, participants used a median of eight tablets (interquartile range 1–18 tablets) after discharge, 23.5% used no opioids, and 23.0% used all opioids. Each of the models demonstrated high accuracy predicting postdischarge opioid use (concordance index range 0.74–0.76 for all models). We selected the reduced model as our final model given its similar model performance with the fewest number of predictors, all obtained from the EHR (inpatient opioid use, tobacco use, and depression or anxiety).

CONCLUSION:

A model with three predictors readily found in the EHR—inpatient opioid use, tobacco use, and depression or anxiety—accurately estimated postdischarge opioid use. This represents an opportunity for individualizing opioid prescriptions after cesarean birth.
LILRB4, an immune checkpoint on myeloid cells
Authors: Yang Ting , Qian Yixin , Liang Xiaoting , Wu Jianbo , Zou Ming , Deng Mi
Published: May 2022

Leukocyte immunoglobulin-like receptor B4 (LILRB4) is an inhibitory receptor in the LILR family mainly expressed on normal and malignant human cells of myeloid origin. By binding to ligands, LILRB4 is activated and subsequently recruits adaptors to cytoplasmic immunoreceptor tyrosine inhibitory motifs to initiate different signaling cascades, thus playing an important role in physiological and pathological conditions, including autoimmune diseases, microbial infections, and cancers. In normal myeloid cells, LILRB4 regulates intrinsic cell activation and differentiation. In disease-associated or malignant myeloid cells, LILRB4 is significantly correlated with disease severity or patient survival and suppresses T cells, thereby participating in the pathogenesis of various diseases. In summary, LILRB4 functions as an immune checkpoint on myeloid cells and may be a promising therapeutic target for various human immune diseases, especially for cancer immunotherapy.
Pancreas Transplantation for Type 2 Diabetes: A Systematic Review, Critical Gaps in the Literature, and a Path Forward
Authors: Amara Dominic , Hansen Keith S. , Kupiec-Weglinski Sophie A. , Braun Hillary J. , Hirose Ryutaro , Hilton Joan F. , Rickels Michael R. , Odorico Jon S. , Stock Peter G.
Published: May 2022

Pancreas transplantation in patients with type 2 diabetes (T2D) remains relatively uncommon compared with pancreas transplantation in patients with type 1 diabetes (T1D); however, several studies have suggested similar outcomes between T2D and T1D, and the practice has become increasingly common. Despite this growing interest in pancreas transplantation in T2D, no study has systematically summarized the data to date. We systematically reviewed the literature on pancreas transplantation in T2D patients including patient and graft survival, glycemic control outcomes, and comparisons with outcomes in T2D kidney transplant alone and T1D pancreas transplant recipients. We searched biomedical databases from January 1, 2000, to January 14, 2021, and screened 3314 records, of which 22 full texts and 17 published abstracts met inclusion criteria. Full-text studies were predominantly single center (73%), whereas the remaining most often studied the Organ Procurement and Transplantation Network database. Methodological quality was mixed with frequent concern for selection bias and concern for inconsistent definitions of both T2D and pancreas graft survival across studies. Overall, studies generally reported favorable patient survival, graft survival, and glycemic control outcomes for pancreas transplantation in T2D and expressed a need to better characterize the T2D patients who would benefit most from pancreas transplantation. We suggest guidance for future studies, with the aim of supporting the safe and evidence-based treatment of end-stage T2D and judicious use of scarce resources.
Reporting of RT-PCR cycle threshold (Ct) values during the first wave of COVID-19 in Qatar improved result interpretation in clinical and public health settings
Authors: Coyle Peter V. , Al Molawi Naema Hassan , Kacem Mohamed Ali Ben Hadj , El Kahlout Reham Awni , Al Kuwari Einas , Al Khal Abdullatif , Gillani Imtiaz , Jeremijenko Andrew , Saeb Hatoun , Al Thani Mohammad , Bertollini Roberto , Abdul Rahim Hanan F. , Chemaitelly Hiam , Tang Patrick , Latif Ali Nizar , Al Kaabi Saad , Al Maslamani Muna A. Rahman S. , Morris Brendan David , Al-Ansari Nasser , Kaleeckal Anvar Hassan , Abu Raddad Laith J.
Published: May 2022

Introduction. The cycle threshold (Ct) value in real-time PCR (RT-PCR) is where a target-specific amplification signal becomes detectable and can infer viral load, risk of transmission and recovery. Use of Ct values in routine practice is uncommon.

Gap Statement. There is a lack of routine use of Ct values when reporting RT-PCR results in routine practice.

Aim. To automatically insert Ct values and interpretive comments when reporting SARS-CoV-2 RT-PCR to improve patient management.

Methodology. Routine Ct values across three different RT-PCR platforms were reviewed for concordance at presentation and clearance in patients with COVID-19. An indicative threshold (IT) linked to viral clearance kinetics was defined at Ct30 to categorize Ct values as low and high, reflecting high and low viral loads respectively.

Results. The different gene targets of each platform showed high correlation and kappa score agreement (P<0.001). Average Ct values were automatically generated with values ≤Ct30 reported as positive and >Ct30 as reactive; interpretive comments were added to all reports. The new reporting algorithm impacted on: physician interpretation of SARS-CoV-2 results; patient management and transfer; staff surveillance; length of stay in quarantine; and redefinition of patient recovery.

Conclusion. Incorporation of Ct values into routine practice is possible across different RT-PCR platforms and adds useful information for patient management. The use of an IT with interpretive comments improves clinical interpretation and could be a model for reporting other respiratory infections. Withholding Ct values wastes useful clinical data and should be reviewed by the profession, accreditation bodies and regulators.
Robustness test of the spacegroupMining model for determining space groups from atomic pair distribution function data
Authors: Lan Ling , Liu Chia-Hao , Du Qiang , Billinge Simon J. L.
Published: May 2022

Machine learning models based on convolutional neural networks have been used for predicting space groups of crystal structures from their atomic pair distribution function (PDF). However, the PDFs used to train the model are calculated using a fixed set of parameters that reflect specific experimental conditions, and the accuracy of the model when given PDFs generated with different choices of these parameters is unknown. In this work, the results of the top-1 accuracy and top-6 accuracy are robust when applied to PDFs of different choices of experimental parameters r
max, Q
max, Q
damp and atomic displacement parameters.
Quantifying signal quality in scanning transmission X-ray microscopy
Authors: Watts Benjamin , Finizio Simone , Raabe Jörg
Published: May 2022

While the general effects of experimental conditions such as photon flux and sample thickness on the quality of data acquired by scanning transmission X-ray microscopy (STXM) are widely known at a basic level, the specific details are rarely discussed. This leaves the community open to forming misconceptions that can lead to poor decisions in the design and execution of STXM measurements. A formal treatment of the uncertainty and distortions of transmission signals (due to dark counts, higher-order photons and poor spatial or spectral resolution) is presented here to provide a rational basis for the pursuit of maximizing data quality in STXM experiments. While we find an optimum sample optical density of 2.2 in ideal conditions, the distortions considered tend to have a stronger effect for thicker samples and so ∼1 optical density at the analytical energy is recommended, or perhaps even thinner if significant distortion effects are expected (e.g. lots of higher-order light is present in the instrument). (Note that X-ray absorption calculations based on simple elemental composition do not include near-edge resonances and so cannot accurately represent the spectral resonances typically employed for contrast in STXM.) Further, we present a method for objectively assessing the merits of higher-order suppression in terms of its impact on the quality of transmission measurements that should be useful for the design of synchrotron beamlines.
Step-stool conformation of a cyclic Schiff base derived from ethylenediamine and heptane-2,4,6-trione: evidence for partial hydrolysis in metal coordination
Authors: Ranaweera Samantha A. , Bruno Donnadieu , Henry W. P. , White Mark. G.
Published: May 2022

A Schiff base derived from ethylenediamine and heptane-2,4,6-trione, namely, 5,9,14,18-tetramethyl-1,4,10,13-tetraazacyclooctadeca-5,8,14,17-tetraene-7,16-dione (C18H28N4O2), abbreviated H4daaden, was prepared and characterized for the first time by single-crystal X-ray diffraction. The atoms of the Schiff base occupy two different planes and thus the molecule is essentially nonplanar. An axis running through the C—C atoms of the ethylenediamine groups separate the two planes and these two planes are connected by bridging ethylene groups showing an angle of 117.34 (8)°. As a result, the side view of the molecule shows a `step-stool' conformation. The nonplanar nature of the Schiff base plays an important role in metal coordination, which leads to partial hydrolysis of the ring structure.
Katerina Kimmorley and Pollinate Group: eradicating energy poverty by empowering women through solar energy
Authors: Faheem Hadiya , Dutta Sanjib
Published: May 2022

Study level/applicability

MBA/MS level programs.

Subject area

Social entrepreneurship, sustainability and business strategy.

Case overview

The case discusses about how social entrepreneur Katerina Kimmorley founded Pollinate Energy with five of her friends to provide solar lights to the urban slum dwellers in Bengaluru, the capital city of Karnataka, a state in the Southern part of India. The company recruited people known as “Pollinators” for distributing their solar lights to the communities on installments making it affordable to them. To scale-up its sustainable energy initiatives and expand its global reach, Pollinate Energy merged with the US-based solar energy company Empower Generation in 2018 to form Pollinate Group. Since the company was making losses and was a nonprofit organization, the new CEO of Pollinate Group Sujatha Ramani and the senior management team had to tackle the challenge of scaling up the company while financially empowering women microentrepreneurs from marginalized communities.

Expected learning outcomes

Study Pollinate Energy’s business model and explore ways in which it can be made sustainable. Discuss the personality traits of Kimmorley which contributed to her success. Discuss how the merger with Empower Generation will help Pollinate Group in expanding its global reach. Explore ways in which the venture can be scaled up further.

Social implications

Pollinate Group focused on women empowerment to tackle the gender inequality challenge. The company provided equal opportunities for men and women, thereby removing discrimination from access to opportunities, sources, services and promotion of equal rights.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS 3: Entrepreneurship