bluuebunny/crossref_metadata_2025 huggingface dataset:
I
Authors: Saunders Max
Published: June 2023

I have, I am aware, told this story in a very rambling way so that it may be difficult for anyone to find their path through what may be a sort of maze. I cannot help it. I have stuck to my idea of being...
IV
Authors: Saunders Max
Published: June 2023

And it seemed to her to be in tune with the mood, with the hour, and with the woman in front of her to say that she knew Edward was dying of love for her and that she was dying of love for Edward. For...
The Camel’s Back
Authors: Bryer Jackson R.
Published: June 2023

The glazed eye of the tired reader resting for a second on the above title will presume it to be merely metaphorical. Stories about the cup and the lip and the bad penny and the new broom rarely have anything to do with cups...
Porcelain and Pink
Authors: Bryer Jackson R.
Published: June 2023

A room in the down-stairs of a summer cottage. High around the wall runs an art frieze of a fisherman with a pile of nets at his feet and a ship on a crimson ocean, a fisherman with a pile of nets at his feet...
Mr. Icky
Authors: Bryer Jackson R.
Published: June 2023

The Scene is the Exterior of a Cottage in West Issacshire on a desperately Arcadian afternoon in August.
mr. icky, quaintly dressed in the costume of an Elizabethan peasant, is pottering and doddering among the pots and dods. He is an old man,...
The Clinical Picture
Authors: Freud Sigmund
Published: June 2023

I showed in my book The Interpretation of Dreams, published in 1900, that dreams in general can be interpreted, and that once the work of interpretation is completed they can be replaced by clearly formed ideas that fit intellectually into a certain...
The First Dream
Authors: Freud Sigmund
Published: June 2023

Just as we had the prospect of casting light on an obscure part of Dora’s childhood by using material that called for analysis, Dora told me that on one night recently she had had a dream, one she had dreamed several times before in...
The Second Dream
Authors: Freud Sigmund
Published: June 2023

A few weeks after her first dream, Dora had her second dream, and when I had dealt with that the analysis was broken off. This dream cannot be made quite so transparent as the first, but it provided welcome confirmation of an assumption that...
The Confusions of Young Törless
Authors: Musil Robert
Published: June 2023

Set in a boarding school in a remote area of the Habsburg Empire at the turn of the last century, The Confusions of Young Törless is an intense study of an adolescent’s psychological development as he struggles to come to terms with his conflicting emotions. Through his relationship with two other boys Törless is led into sadistic and sexual encounters with a third pupil which both repel and fascinate him. Estranged from everyday life, Törless gradually learns to accept his experiences and describe them with analytical precision.

The novel is based on the author’s own experiences at an Austrian military academy. A school story with a difference, Törless extends the scope of fiction with its non-judgemental presentation of transgressive sexuality and violence. It is a profoundly disturbing exploration of a non-moral outlook on life and of dictatorial attitudes that prefigure the outbreak of the First World War and the rise of fascism.
Pleiotropic Association of CACNA1C Variants With Neuropsychiatric Disorders
Authors: Wang Zuxing , Lin Xiandong , Luo Xinqun , Xiao Jun , Zhang Yong , Xu Jianying , Wang Shibin , Zhao Fen , Wang Huifen , Zheng Hangxiao , Zhang Wei , Lin Chen , Tan Zewen , Cao Liping , Wang Zhiren , Tan Yunlong , Chen Wenzhong , Cao Yuping , Guo Xiaoyun , Pittenger Christopher , Luo Xingguang
Published: June 2023

Background

Neuropsychiatric disorders are highly heritable and have overlapping genetic underpinnings. Single nucleotide polymorphisms (SNPs) in the gene CACNA1C have been associated with several neuropsychiatric disorders, across multiple genome-wide association studies.

Method

A total of 70,711 subjects from 37 independent cohorts with 13 different neuropsychiatric disorders were meta-analyzed to identify overlap of disorder-associated SNPs within CACNA1C. The differential expression of CACNA1C mRNA in five independent postmortem brain cohorts was examined. Finally, the associations of disease-sharing risk alleles with total intracranial volume (ICV), gray matter volumes (GMVs) of subcortical structures, cortical surface area (SA), and average cortical thickness (TH) were tested.

Results

Eighteen SNPs within CACNA1C were nominally associated with more than one neuropsychiatric disorder (P < .05); the associations shared among schizophrenia, bipolar disorder, and alcohol use disorder survived false discovery rate correction (five SNPs with P < 7.3 × 10−4 and q < 0.05). CACNA1C mRNA was differentially expressed in brains from individuals with schizophrenia, bipolar disorder, and Parkinson’s disease, relative to controls (three SNPs with P < .01). Risk alleles shared by schizophrenia, bipolar disorder, substance dependence, and Parkinson’s disease were significantly associated with ICV, GMVs, SA, or TH (one SNP with P ≤ 7.1 × 10−3 and q < 0.05).

Conclusion

Integrating multiple levels of analyses, we identified CACNA1C variants associated with multiple psychiatric disorders, and schizophrenia and bipolar disorder were most strongly implicated. CACNA1C variants may contribute to shared risk and pathophysiology in these conditions.
A longitudinal study of infant 24-hour sleep: comparisons of sleep diary and accelerometer with different algorithms
Authors: Liu Tiange , Benjamin-Neelon Sara E
Published: June 2023

Study Objectives

To longitudinally compare sleep/wake identification and sleep parameter estimation from sleep diaries to accelerometers using different algorithms and epoch lengths in infants.

Methods

Mothers and other caregivers from the Nurture study (southeastern United States, 2013–2018) reported infants’ 24-hour sleep in sleep diaries for 4 continuous days, while infants concurrently wore accelerometers on the left ankle at 3, 6, 9, and 12 months of age. We applied the Sadeh, Sadeh Infant, Cole, and Count-scaled algorithm to accelerometer data at 15 and 60 seconds epochs. For sleep/wake identification, we assessed agreement by calculating epoch-by-epoch percent agreement and kappas. We derived sleep parameters from sleep diaries and accelerometers separately and evaluated agreement using Bland–Altman plots. We estimated longitudinal trajectories of sleep parameters using marginal linear and Poisson regressions with generalized estimation equation estimation.

Results

Among the 477 infants, 66.2% were black and 49.5% were female. Agreement for sleep/wake identification varied by epoch length and algorithm. Relative to sleep diaries, we observed similar nighttime sleep offset, onset, and total nighttime sleep duration from accelerometers regardless of algorithm and epoch length. However, accelerometers consistently estimated about 1 less nap per day using the 15 seconds epoch, 70 and 50 minutes’ shorter nap duration per day using the 15 and 60 seconds epoch, respectively; but accelerometers estimated over 3 times more wake after nighttime sleep onset (WASO) per night. Some consistent sleep parameter trajectories from 3 to 12 months from accelerometers and sleep diaries included fewer naps and WASOs, shorter total daytime sleep, longer total nighttime sleep, and higher nighttime sleep efficiency.

Conclusions

Although there is no perfect measure of sleep in infancy, our findings suggest that a combination of accelerometer and diary may be needed to adequately measure infant sleep.
Emerging research on postacute COVID-19 complications
Authors: Williams Sydne
Published: June 2023

An estimated 21.5% of patients in the United States who have had COVID-19 report development of a prolonged postviral syndrome that has been called postacute sequelae of COVID-19 (PASC). Symptoms can range from very mild to debilitating damage to organ systems caused directly by the virus and indirectly by the body's inflammatory response. Research into defining PASC and discovering effective treatments is ongoing. This article discusses the common presentations of PASC in patients who have had COVID-19; describes specific effects on the pulmonary, cardiovascular, and central nervous systems; and identifies potential treatments based on current literature.
Electronic Reminder to Transition Care After Hypertensive Disorders of Pregnancy
Authors: Triebwasser Jourdan E. , Lewey Jennifer , Walheim Lauren , Sehdev Harish M. , Srinivas Sindhu K.
Published: June 2023

OBJECTIVE:

Scalable interventions are needed to improve preventive care for those with increased cardiovascular disease (CVD) risk identified during pregnancy. We hypothesized that an automated reminder message for clinicians (nudge) would increase counseling at the postpartum visit on patient transitions of care.

METHODS:

We conducted a single-center, randomized controlled trial including birthing people with a hypertensive disorder of pregnancy evaluating a nudge compared with usual care. The nudge, including counseling phrases and patient-specific information on hypertensive diagnosis, was sent to the obstetric clinician through the electronic medical record up to 7 days before the postpartum visit. The primary outcome was documentation of counseling on transitions of care to primary care or cardiology. Secondary outcomes were documentation of CVD risk, use of counseling phrases, and preventive care visit within 6 months. A sample size of 94 per group (n=188) was planned to compare the nudge intervention with usual care; given the anticipated loss to follow-up, the sample size was increased to 222. Intention-to-treat analyses were performed, with P<.05 considered significant.

RESULTS:

From February to June 2021, 392 patients were screened, and 222 were randomized and analyzed. Of these, 205 (92.3%) attended a postpartum visit. Groups were similar, but more women in the usual care group had diabetes (16.1% vs 6.7%, P=.03). After adjustment for diabetes, patients in the nudge group were more likely to have documented counseling on transitions of care (38.8% vs 26.2%, adjusted relative risk [aRR] 1.53, 95% CI 1.02–2.31), CVD risk (21.4% vs 8.4%, aRR 2.57, 95% CI 1.20–5.49), and use of aspirin in a future pregnancy (14.3% vs 1.9%, aRR 7.49, 95% CI 1.66–33.93). Counseling phrases were used more often in the nudge group (11.2% vs 0.9%, aRR 12.27, 95% CI 1.50–100.28). Preventive care visit attendance did not differ by group (22.1% vs 24.6%, aRR 0.91, 95% CI 0.57–1.47).

CONCLUSION:

A timely electronic reminder to obstetric clinicians improved counseling about transitions of care after hypertensive disorders of pregnancy but did not result in increased preventive care visit attendance.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT04660032.
Plasma Lipid Analysis of Simultaneous Application of Radiofrequency Synchronized With HIFEM for Fat Reduction in Same-Day Multiple Sessions
Authors: Weiss Robert A.
Published: June 2023

BACKGROUND

High-intensity focused electromagnetic field (HIFEM) and synchronized radiofrequency (RF) technologies have been shown to be safe and effective on multiple body parts

OBJECTIVE

To determine the plasma lipid levels and liver function tests of consecutive HIFEM + RF procedures delivered on the same day.

METHODS

Eight women and 2 men (24–59 years, BMI 22.4–30.6 kg/m2) underwent 4 30-minute consecutive HIFEM + RF procedures. The treated area differed according to gender (females: abdomen and lateral and inner thighs; males: abdomen and front and back thighs). Liver function (aspartate aminotransferase [AST], alanine aminotransferase [ALT], gamma-glutamyltransferase [GGT], alkaline phosphatase [ALP]) and lipid profile (cholesterol, high-density lipoprotein [HDL], low-density lipoprotein [LDL], triglycerides [TG]) was monitored from blood samples drawn before the treatment, 1 hour, 24 to 48 hours, and 1 month after treatment. The subject's satisfaction, comfort, abdominal circumference, and digital photographs were also monitored.

RESULTS

All 10 patients completed planned treatments and follow-up blood draws. No significant fluctuation or notable deviation in the measured blood parameters was observed. The average values during the study were in a range of AST 15.7 to 16.7IU/L, ALT 11.9 to 13.4IU/L, GGT 11.6 to 13.8IU/L, and ALP 71.4 to 77.2IU/L, TG 1.0 mmol/L, HDL 1.7 mmol/L, LDL 3.0 mmol/L, and cholesterol 5.0 to 5.1 mmol/L corresponded to the normal ranges. Subjects reported high comfort during the treatment and satisfaction with their results. No adverse event occurred.

CONCLUSION

Plasma levels remained stable and normal or lipids and LFTs for multiple same-day treatments of RF plus HIFEM.
Relationship between anterior capsule opening and direction of intraocular lens decentration
Authors: Nagata Mayumi , Hanemoto Tsukasa , Matsushima Hiroyuki , Senoo Tadashi
Published: June 2023

Purpose:

To compare intraocular lens (IOL) decentration between patients in whom the continuous curvilinear capsulorhexis (CCC) completely covers the IOL optic and those in whom it incompletely covers the IOL optic and determine how an incompletely covered CCC affects the IOL position.

Setting:

Tertiary hospital in Japan.

Design:

Single-center retrospective study.

Methods:

57 eyes of 57 patients (mean age 70.8 ± 6.2 years) that underwent phacoemulsification and IOL (SN60WF) implantation in the bag between April 2010 and April 2015 were included in this study. The patients were classified based on whether the CCC completely (CC group) or incompletely (NCC group) covered the IOL optic using an anterior eye segment analysis system (EAS-1000). The IOL decentration of the groups was analyzed using EAS-1000 at 1 week, 1 month, 3 months, and 6 months postoperatively and compared. The relationship between the NCC location and the IOL direction at 3 months postoperatively was analyzed.

Results:

The NCC group (25 eyes) had a significantly higher amount of IOL decentration than the CC group (32 eyes) at 1 week, 1 month, 3 months, and 6 months postoperatively (P < .05). There was a correlation between the direction of IOL decentration and the NCC location, and IOL decentration in the NCC group occurred in the opposite direction to the NCC area.

Conclusions:

An anterior capsule opening that completely covers the IOL optic is important to control IOL decentration.
Health Literacy Implementation Principles: Pediatric Colorectal Program Development
Authors: Pasarón Raquel , Calisto Juan Luis , Gurucharri Brian P. , Levitt Marc A.
Published: June 2023

Background: As part of the course requirement for a post-graduate acute care pediatric nurse practitioner program, a patient/family education project was presented using health literacy principles to support the materials developed. The project represents previously implemented materials for a newly developed pediatric colorectal program; this is a retrospective synthesis. Purpose: Understanding and including the population served when designing, implementing, and evaluating health information and services are imperative in emerging health literacy foci. Previously health literacy focused on patients and their skills or deficits that were then linked to health outcomes. Later the focus shifted to the clinician's rigor and skill in communication. New developments in health literacy shift the focus from skills, public, and staff to an emphasis on the interplay of the environment, which either limits or facilitates health literacy. Methods: Pediatric colorectal care gap analysis from 2018–2021 for the state where the program was created provides a needs assessment of the population of interest. A descriptive narrative of the process for designing, implementing, and evaluating health literate services is presented. Information on current literature and materials to integrate health literacy principles is explored. Conclusion: This article contributes to a need for more available literature on developing health literacy in pediatric colorectal program development and care. The findings challenge clinicians to incorporate health literacy best practice attributes in healthcare environments and monitor and use quality improvement methods that address health disparities.
The changing face of cardiogenic shock: definitions, epidemiology, and severity assessment
Authors: Jentzer Jacob C. , Baran David A.
Published: June 2023

Purpose of review

Cardiogenic shock (CS) has been recognized for >50 years, most commonly in the setting of myocardial infarction. This review covers recent advances in the definitions, epidemiology and severity assessment of cardiogenic shock.

Recent findings

In this review, the authors discuss the evolving definitions of cardiogenic shock, detailing the early approaches as well as more contemporary ideas. The epidemiology of CS is reviewed and then granular detail on the assessment of shock severity is provided including the role of lactate measurement and invasive hemodynamic assessment. The development of the Society for Cardiac Angiography and Intervention (SCAI) consensus statement on Classification of Cardiogenic Shock is reviewed by the principal authors. The revised SCAI Shock document is reviewed as well and the future directions for assessment of shock along with clinical applications are reviewed.

Cardiogenic shock mortality has not changed in a significant way in many years. Recent advances such as more granular assessment of shock severity have the potential to improve outcomes by allowing research to separate the patient groups which may respond differently to various therapies.
Being a Hospice Nurse in Times of the COVID-19 Pandemic
Authors: Bové Hanne Mørkenborg , Noer Vibeke Røn , Mousing Camilla Askov
Published: June 2023

End-of-life care changed during the COVID-19 pandemic, and the previous prevailing hospice philosophy and essential values of hospice care were suddenly under pressure. The aim was to explore hospice nurses' lived experience of providing end-of-life care to patients admitted in an out-hospital hospice setting during the COVID-19 pandemic. Data consist of 10 individual in-depth interviews of hospice nurses. A purposive sampling strategy was used, and the data collection and analysis was guided by a descriptive phenomenology. Providing end-of-life care was described through an existential dimension and a practical-related dimension. The pandemic and the ensuing constraints created an unfamiliar gap, triggering insecurity and unfamiliarity within nursing. Findings are elaborated in the following constituents: being a hospice nurse and providing end-of-life care. The latter constituent was further elucidated in additional perspectives: a new job position and bending the rules. Providing end-of-life care during the COVID-19 regime was a highly challenging and distressing experience due to the coercion of maintaining rules and restrictions as well as providing care. An experience of having to reinvent and work within a new agenda was present. Furthermore, the nurses experienced significant loss of job satisfaction and may be morally injured as well as highly exposed to secondary traumatization.
Reliability and Agreement of Automated Head Measurements From 3-Dimensional Photogrammetry in Young Children
Authors: Abdel-Alim Tareq , Tio Pauline , Kurniawan Melissa , Mathijssen Irene , Dirven Clemens , Niessen Wiro , Roshchupkin Gennady , van Veelen Marie-Lise
Published: June 2023

This study aimed to assess the reliability and agreement of automated head measurements using 3-dimensional (3D) photogrammetry in young children. Specifically, the study evaluated the agreement between manual and automated occipitofrontal circumference (OFC) measurements (n = 264) obtained from 3D images of 188 patients diagnosed with sagittal synostosis using a novel automated method proposed in this study. In addition, the study aimed to determine the interrater and intrarater reliability of the automatically extracted OFC, cephalic index, and volume. The results of the study showed that the automated OFC measurements had an excellent agreement with manual measurements, with a very strong regression score (R
2 = 0.969) and a small mean difference of −0.1 cm (−0.2%). The limits of agreement ranged from −0.93 to 0.74 cm, falling within the reported limits of agreement for manual OFC measurements. High interrater and intrarater reliability of OFC, cephalic index, and volume measurements were also demonstrated. The proposed method for automated OFC measurements was found to be a reliable alternative to manual measurements, which may be particularly beneficial in young children who undergo 3D imaging in craniofacial centers as part of their treatment protocol and in research settings that require a reproducible and transparent pipeline for anthropometric measurements. The method has been incorporated into CraniumPy, an open-source tool for 3D image visualization, registration, and optimization, which is publicly available on GitHub (https://github.com/T-AbdelAlim/CraniumPy).
Introduction to the special issue Amphibian immunity: stress, disease and ecoimmunology
Authors: Assis Vania Regina , Robert Jacques , Titon Stefanny Christie Monteiro
Published: June 2023

Amphibian populations have been declining worldwide, with global climate changes and infectious diseases being among the primary causes of this scenario. Infectious diseases are among the primary drivers of amphibian declines, including ranavirosis and chytridiomycosis, which have gained more attention lately. While some amphibian populations are led to extinction, others are disease-resistant. Although the host's immune system plays a major role in disease resistance, little is known about the immune mechanisms underlying amphibian disease resistance and host–pathogen interactions. As ectotherms, amphibians are directly subjected to changes in temperature and rainfall, which modulate stress-related physiology, including immunity and pathogen physiology associated with diseases. In this sense, the contexts of stress, disease and ecoimmunology are essential for a better understanding of amphibian immunity. This issue brings details about the ontogeny of the amphibian immune system, including crucial aspects of innate and adaptive immunity and how ontogeny can influence amphibian disease resistance. In addition, the papers in the issue demonstrate an integrated view of the amphibian immune system associated with the influence of stress on immune–endocrine interactions. The collective body of research presented herein can provide valuable insights into the mechanisms underlying disease outcomes in natural populations, particularly in the context of changing environmental conditions. These findings may ultimately enhance our ability to forecast effective conservation strategies for amphibian populations.

This article is part of the theme issue ‘Amphibian immunity: stress, disease and ecoimmunology’.
Contrasting effects of transdermal and implant corticosterone treatments in the American bullfrog wound healing
Authors: Madelaire Carla B. , Silva Diego P. , Titon Stefanny C. M. , Lamadrid-Feris Faride , Floreste Felipe R. , Titon Jr Braz , Gomes Fernando R.
Published: June 2023

Glucocorticoid (GC) release is triggered by adverse stimuli that activate the hypothalamus-pituitary-adrenal/interrenal axis. Glucocorticoids may enhance or suppress immune functions depending on the level of elevation. In this study, we investigated the effects of transient and chronic increase of corticosterone (CORT) on the wound healing of the American bullfrog. Frogs were submitted to a daily transdermal hormonal application that acutely elevated CORT plasma levels, or vehicle as a control. Other frogs were surgically implanted with a silastic tube filled with CORT that resulted in chronic elevation of CORT plasma levels or received empty implants as a control. A dermal biopsy was performed to create a wound and was photographed every 3 days. Individuals treated with transdermal CORT started healing faster than their control 32 days after the biopsy. Frogs that received CORT implants tended to heal slower than control subjects. Plasma bacterial killing ability was not affected by treatment, which reinforces the constitutive nature of this innate immune trait. By the end of the experiment, frogs from the acute CORT treatment had smaller wounds compared with those receiving the CORT-filled implants, highlighting the differential effects of acute (immunoenhancing) and chronic (immunosuppressive) elevation of CORT plasma levels.

This article is part of the theme issue ‘Amphibian immunity: stress, disease and ecoimmunology’.
Effects of exogenous elevation of corticosterone on immunity and the skin microbiome of eastern newts (
Notophthalmus viridescens
)
Authors: Pereira Kenzie E. , Bletz Molly C. , McCartney Julia A. , Woodhams Douglas C. , Woodley Sarah K.
Published: June 2023

The amphibian chytrid fungus,
Batrachochytrium salamandrivorans
(
Bsal
) threatens salamander biodiversity. The factors underlying
Bsal
susceptibility may include glucocorticoid hormones (GCs). The effects of GCs on immunity and disease susceptibility are well studied in mammals, but less is known in other groups, including salamanders. We used
Notophthalmus viridescens
(eastern newts) to test the hypothesis that GCs modulate salamander immunity. We first determined the dose required to elevate corticosterone (CORT; primary GC in amphibians) to physiologically relevant levels. We then measured immunity (neutrophil lymphocyte ratios, plasma bacterial killing ability (BKA), skin microbiome, splenocytes, melanomacrophage centres (MMCs)) and overall health in newts following treatment with CORT or an oil vehicle control. Treatments were repeated for a short (two treatments over 5 days) or long (18 treatments over 26 days) time period. Contrary to our predictions, most immune and health parameters were similar for CORT and oil-treated newts. Surprisingly, differences in BKA, skin microbiome and MMCs were observed between newts subjected to short- and long-term treatments, regardless of treatment type (CORT, oil vehicle). Taken together, CORT does not appear to be a major factor contributing to immunity in eastern newts, although more studies examining additional immune factors are necessary.

This article is part of the theme issue ‘Amphibian immunity: stress, disease and ecoimmunology’.
FEBRILE SEPSIS:  FIRST REPORT OF HUMAN DISEASE DUE TO PAENIBACILLUS SILVAE

Authors: BENEDETTI PAOLO , Vecchia Ilaria Dalla , Fasan Daniele , Pegoraro Manuela
Published: June 2023

ABSTRACT
Introduction. Paenibacillus species are saprophytes widely distributed in nature and rarely associated with overt human infection. Most of cases have been described in people with important comorbidities and/or immunodepression. We report here what is, to the best of our knowledge, the first documented case of human disease due to P. silvae, so far considered an exclusively environmental micro-organism.
Case presentation. A 57-year-old female patient was referred to our Unit after a 2-month history of remittent fever. Upon admission, septic state and bacteraemia was revealed; P. sylvae was speciated by 16S-rRNA gene amplification and sequencing MALDI-TOF.  The patient became afebrile after 9 days of antibiotic treatment and was completely cured after a 2-week regimen with I.V. amoxicillin-clavulanate plus oral doxycycline.
Conclusion. The patient did not report any episode of infection occurred previously. Most of the well-known risk factors to Paenibacillus bacteraemia, i.e., invasive procedures, use of intravenous drugs, and foreign bodies could be revealed, although her immune system was probably impaired due to obesity and heavy smoking. We suggest that the isolation of bacteria belonging to the Paenibacillus genus should not be disregarded, since there is accumulating evidence that these organisms may cause disease even in immunocompetent subjects.
Low-Dose Naltrexone use for the management of post-acute sequelae of COVID-19
Authors: Bonilla Hector , Tian Lu , Marconi Vincent C. , Shafer Robert , McComsey Grace A. , Miglis Mitchel , Yang Philip , Geng Linda N.
Published: June 2023

Post-Acute Sequelae of SARS-CoV-2 (PASC), also known as Long COVID, is globally estimated to have affected up to 40-50% of individuals who were infected with SARS-CoV-2. The causes of PASC are being investigated, and there are no established therapies. One of the leading hypotheses for the cause of PASC is the persistent activation of innate immune cells with increased systemic inflammation. Naltrexone is a medication with anti-inflammatory and immunomodulatory properties that has been used in other conditions that overlap with PASC. In this study we performed retrospective review of a clinical cohort of 59 patients at a single academic center who received low-dose naltrexone (LDN) off-label as a potential therapeutic intervention for PASC. The use of LDN was associated with improved clinical symptoms (fatigue, brain fog, post exertional malaise/PEM, unrefreshing sleep, sleep pattern, and headache), fewer number of symptoms, and better functional status. This observational finding warrants further testing in rigorous, randomized, placebo-controlled clinical trials.

Highlights

-

The off-label use of low-dose naltrexone is a promising drug intervention candidate for the management of post-COVID conditions.

-

Low-dose naltrexone has anti-inflammatory and immunomodulatory properties which may benefit those with PASC where persistent inflammation is the causative pathway.

-

This potential benefit of LDN warrants further testing in rigorous randomized, placebo-controlled clinical trials.
Sustainability Indexes as Possible Predictors of Excess Mortality across OECD Countries during the Covid-19 Pandemic
Authors: Liu Lee
Published: June 2023

This study considered the Sustainable Development Goals (SDG) Index, Human Development Index (HDI), and Environmental Performance Index (EPI) as sustainability indexes and explored their potential effectiveness as predictors of Covid-19 excess mortality among countries in the Organization for Economic Cooperation and Development (OECD). The results indicated strong negative correlations between each index and Covid-19 excess mortality. Each of the indexes was able to consistently predict variations in excess mortality in the regression models. Such findings contribute to the current discussion on what lessons we should take away from the Covid-19 pandemic, specifically whether sustainability indexes may be useful in assessing Covid-19 outcomes. It is valuable to further examine the role sustainable policies and practices can play in preparing for future crises, as it has been demonstrated that social, economic, and environmental factors influenced the ability of a country to mitigate the impact of Covid-19. Overall, the most effective way for a country to both prevent and prepare for the next crisis is to improve health, education, and standard of living for its people, protect the environment, and achieve sustainability.
Select EZH2 inhibitors enhance the viral mimicry effects of DNMT inhibition through a mechanism involving calcium-calcineurin-NFAT signaling
Authors: Chomiak Alison A. , Tiedemann Rochelle L. , Liu Yanqing , Kong Xiangqian , Cui Ying , Thurlow Kate , Cornett Evan M. , Topper Michael J. , Baylin Stephen B. , Rothbart Scott B.
Published: June 2023

DNA methyltransferase (DNMT) inhibitors are FDA-approved for various hematological malignancies but have limited efficacy in solid tumors. DNA hypomethylation with these drugs is associated with elevated lysine 27 tri-methylation on histone H3 (H3K27me3). We hypothesized that this EZH2-dependent repressive mark limits the full potential of DNMT inhibition. Here, we show in cell line and tumoroid models of colorectal cancer, that low-dose DNMT inhibition sensitizes cells to selective EZH2 inhibitors that have limited single agent toxicity, and that EZH2 inhibition enhances DNMT inhibitor-driven molecular and therapeutic effects. Through integrative epigenomic analyses, we reveal that DNMT inhibition induces H3K27me3 accumulation at genomic regions poised with EZH2. Unexpectedly, combined treatment alters the epigenome landscape to promote transcriptional upregulation of the calcium-calcineurin-NFAT signaling pathway. Blocking this pathway limits the transcriptional activating effects of the drug combination, including expression of transposable elements and innate immune response genes within a viral defense pathway. Consistently, we demonstrate positive correlations between DNMT inhibitor- and innate immune response-associated transcription profiles and calcium signal activation in primary human colon cancer specimens. Collectively, our study demonstrates that compensatory EZH2 activity following DNA hypomethylation presents a barrier to the therapeutic action of DNMT inhibition in colon cancer, reveals a new application of EZH2 inhibitors beyond cancers associated with PRC2 hyperactivity, and links calcium-calcineurin-NFAT signaling to epigenetic therapy-induced viral mimicry.

Highlights

Select EZH2 inhibitors enhance the transcriptional activating and antiproliferative effects of DNA hypomethylating agents in colon cancer cells.

The mechanism involves blockade of H3K27me3 accumulation in regions of the genome poised for PRC2 activity.

DNMT inhibitor + EZH2 inhibitor treatment transcriptionally upregulates calcium-calcineurin- NFAT signaling, and this pathway is necessary for complete induction of viral mimicry and innate immune response pathways.

The therapeutic utility of EZH2 inhibitors may be extended beyond cancers with PRC2 hyperactivity in combination regimens with DNMT inhibitors.
cProSite: A web based interactive platform for online proteomics, phosphoproteomics, and genomics data analysis
Authors: Wang Dunrui , Qian Xiaolan , Du Yi-Chieh Nancy , Sanchez-Solana Beatriz , Chen Kailing , Kanigicherla Madhu , Jenkins Lisa M. , Luo Jason , Eng Sarah , Park Brian , Chen Ben , Yao Xiaozheng , Nguyen Thuong , Tripathi Brajendra K. , Durkin Marian E. , Lowy Douglas R.
Published: June 2023

We developed cProSite, a website that provides online genomics, proteomics, and phosphoproteomics analysis for the data of The National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC). This tool focuses on comparisons and correlations between different proteins and mRNAs of tumors and normal tissues. Our website is designed with biologists and clinicians in mind, with a user-friendly environment and fast search engine. The search results of cProSite can be used for clinical data validation and provide useful strategic information to identify drug targets at proteomic, phosphoproteomic, or genomic levels. The site is available athttp://cprosite.ccr.cancer.gov.

Significance

An interactive database for the expression and correlation for proteins, proteomic phosphorylations, and mRNA levels has been developed for analyzing the molecular alterations between tumors and normal tissues of various tumor types.
Repository of logically consistent real-world Boolean network models
Authors: Pastva Samuel , Šafránek David , Beneš Nikola , Brim Luboš , Henzinger Thomas
Published: June 2023

Recent developments in both computational analysis and data-driven synthesis enable a new era of automated reasoning with logical models (Boolean networks in particular) in systems biology. However, these advancements also motivate an increased focus on quality control and performance comparisons between tools.

At the moment, to illustrate real-world applicability, authors typically test their approaches on small sets of manually curated models that are inherently limited in scope. This further complicates reuse and comparisons, because benchmark models often contain ad hoc modifications or are outright not available.

In this paper, we describe a new, comprehensive, open source dataset of 210+ Boolean network models compiled from available databases and a literature survey. The models are available in a wide range of formats. Furthermore, the dataset is accompanied by a validation pipeline that ensures the integrity and logical consistency of each model. Using this pipeline, we identified and repaired 400+ potential problems in a number of widely used models.
Interleukin-27-induced HIV-resistant dendritic cells suppress reveres transcription following virus entry in an SPTBN1, Autophagy, and YB-1 independent manner
Authors: Imamichi Tomozumi , Chen Qian , Sowrirajan Bharatwaj , Yang Jun , Laverdure Sylvain , Mele Anthony R. , Watkins Catherine , Adelsberger Joseph W. , Higgins Jeanette , Sui Hongyan
Published: June 2023

Interleukin (IL)-27, a member of the IL-12 family of cytokines, induces human immunodeficiency virus (HIV)-resistant monocyte-derived macrophages and T cells. This resistance is mediated via the downregulation of spectrin beta, non-erythrocytic 1 (SPTBN1), induction of autophagy, or suppression of the acetylation of Y-box binding protein-1 (YB-1); however, the role of IL-27 administration during the induction of immature monocyte-derived dendritic cells (iDC) is poorly investigated. In the current study, we investigated the function of IL-27-induced iDC (27DC) on HIV infection. 27DC inhibited HIV infection by 95 ± 3 % without significant changes in the expression of CD4, CCR5, and SPTBN1 expression, autophagy induction and acetylation of YB-1 compared to iDC. An HIV proviral DNA copy number assay displayed that 27DC suppressed reverse transcriptase (RT) reaction without influencing the virus entry. A DNA microarray analysis was performed to identify the differentially expressed genes between 27DC and iDC. Compared to iDC, 51 genes were differentially expressed in 27DC, with more than 3-fold changes in four independent donors. Cross-reference analysis with the reported 2,214 HIV regulatory host genes identified nine genes as potential interests: Ankyrin repeat domain 22, Guanylate binding protein (GBP)-1, -2, -4, -5, Stabilin 1, Serpin family G member 1 (SERPING1), Interferon alpha inducible protein 6, and Interferon-induced protein with tetratricopeptide repeats 3. A knock-down study using si-RNA failed to determine a key factor associated with the anti-HIV activity due to the induction of robust amounts of off-target effects. Overexpression of each protein in cells had no impact on HIV infection. Thus, we could not define the mechanism of the anti-HIV effect in 27DC. However, our findings indicated that IL-27 differentiates monocytes into HIV-resistant DC, and the inhibitory mechanism differs from IL-27-induced HIV-resistant macrophages and T cells.
Accurate integration of multiple heterogeneous single-cell RNA-seq data sets by learning contrastive biological variation
Authors: Zhou Yang , Sheng Qiongyu , Qi Jing , Hua Jiao , Yang Bo , Wan Lei , Jin Shuilin
Published: June 2023

For most biological and medical applications of single-cell transcriptomics, an integrative study of multiple heterogeneous single-cell RNA sequencing (scRNA-seq) data sets is crucial. However, present approaches are unable to integrate diverse data sets from various biological conditions effectively because of the confounding effects of biological and technical differences. We introduce single-cell integration (scInt), an integration method based on accurate, robust cell–cell similarity construction and unified contrastive biological variation learning from multiple scRNA-seq data sets. scInt provides a flexible and effective approach to transfer knowledge from the already integrated reference to the query. We show that scInt outperforms 10 other cutting-edge approaches using both simulated and real data sets, particularly in the case of complex experimental designs. Application of scInt to mouse developing tracheal epithelial data shows its ability to integrate development trajectories from different developmental stages. Furthermore, scInt successfully identifies functionally distinct condition-specific cell subpopulations in single-cell heterogeneous samples from a variety of biological conditions.
Crystal structure and Hirshfeld surface analysis of bis{(Z)-N′-[(E)-(furan-2-yl)methylidene]carbamohydrazonothioato}nickel(II) methanol disolvate
Authors: Azizova Asmet N. , Mammadova Gunay Z. , Çelikesir Sevim Türktekin , Akkurt Mehmet , Bhattarai Ajaya
Published: June 2023

In the title complex, [Ni(C6H6N3OS)2]·2CH3OH, the NiII atom is coordinated by the S and N atoms of two N′-[(Z)-(furan-2-yl)methylidene]carbamohydrazonothioic acid ligands in a distorted square-planar geometry. The two mutual ligands bound to NiII are also connected by C—H...S interactions, while the H atoms of the NH2 group of the ligands form R
4
4(8) motifs with the O atoms of the solvent ethyl alcohol molecules. At the same time, the OH groups of the solvent ethyl alcohol molecules form parallel layers to the (011) plane by the O—H...N interactions with the ligand N atom that is not bonded to the NiII atom.. The layers are connected by van der Waals interactions. A Hirshfeld surface analysis indicates that the most important contacts are H...H (37.7%), C...H/H...C (14.6%), O...H/H...O (11.5%) and S...H/H...S (10.6%).
Simulation of nonuniform transmission lines
Authors: Condon Marissa
Published: June 2023

Purpose

The purpose of the paper is the simulation of nonuniform transmission lines.

Design/methodology/approach

The method involves a Magnus expansion and a numerical Laplace transform. The method involves a judicious arrangement of the governing equations so as to enable efficient simulation.

Findings

The results confirm an effective and efficient numerical solver for inclusion of nonuniform transmission lines in circuit simulation.

Originality/value

The work combines a Magnus expansion and numerical Laplace transform algorithm in a novel manner and applies the resultant algorithm for the effective and efficient simulation of nonuniform transmission lines.
Open access initiatives in European countries: analysis of trends and policies
Authors: Nazim Mohammad , Bhardwaj Raj Kumar
Published: June 2023

Purpose

This paper aims to analyze open access (OA) scholarly publishing patterns as well as OA policies and mandates across European countries.

Design/methodology/approach

The study is based on a descriptive research approach using data from Web resources, directories and bibliographic and citation databases, namely, DOAJ, OpenDOAR, SCImago journal and Country Ranking portal, ROARMAP and Web of Science.

Findings

The findings indicate that the initiatives and measures in Europe that promote OA are adequate. OA journals and digital repositories have progressively increased over the past two decades. Of the total journals (n = 25,231) published worldwide and indexed in Scopus, 53% are published in European countries, with 23.7% being OA journals. In total, 34% of the OA repositories (n = 5,714) are in European countries. The proportion of OA journal papers has grown significantly in all European countries, with a 14.3% annual growth rate. The average proportion of OA publications in European countries is significantly higher (39.07%) than the world average (30.16%), with a clear inclination for making research literature openly accessible via the green OA route (79.41%) compared to the gold OA route (52.30%). Most European research funders and institutions have required researchers to make OA available for their research findings, either by publishing them in OA journals or depositing accepted manuscripts in repositories.

Research limitations/implications

The study analyzed OA trends in Europe; other continents and countries were not included in the analysis. The study only described OA policies and mandates; the extent to which the OA policies and mandates were implemented was not studied. However, the results of the study may be helpful to policymakers, funders, research institutions and universities in other countries in adopting and implementing OA policies and mandates.

Originality/value

To the best of the authors’ knowledge, the study is the first that used multiple data sources for investigating different facets of OA publishing in European countries, including OA journals, digital repositories, research output, mandates and policies for publicly funded research. The findings will be helpful for researchers and policymakers interested in promoting OA adoption among researchers worldwide.
Impact of information consistency in online reviews on consumer behavior in the e-commerce industry: a text mining approach
Authors: Li Qinglong , Park Jaeseung , Kim Jaekyeong
Published: June 2023

Purpose

The current study investigates the impact on perceived review helpfulness of the simultaneous processing of information from multiple cues with various central and peripheral cue combinations based on the elaboration likelihood model (ELM). Thus, the current study develops and tests hypotheses by analyzing real-world review data with a text mining approach in e-commerce to investigate how information consistency (rating inconsistency, review consistency and text similarity) influences perceived helpfulness. Moreover, the role of product type is examined in online consumer reviews of perceived helpfulness.

Design/methodology/approach

The current study collected 61,900 online reviews, including 600 products in six categories, from Amazon.com. Additionally, 51,927 reviews were filtered that received helpfulness votes, and then text mining and negative binomial regression were applied.

Findings

The current study found that rating inconsistency and text similarity negatively affect perceived helpfulness and that review consistency positively affects perceived helpfulness. Moreover, peripheral cues (rating inconsistency) positively affect perceived helpfulness in reviews of experience goods rather than search goods. However, there is a lack of evidence to demonstrate the hypothesis that product types moderate the effectiveness of central cues (review consistency and text similarity) on perceived helpfulness.

Originality/value

Previous studies have mainly focused on numerical and textual factors to investigate the effect on perceived helpfulness. Additionally, previous studies have independently confirmed the factors that affect perceived helpfulness. The current study investigated how information consistency affects perceived helpfulness and found that various combinations of cues significantly affect perceived helpfulness. This result contributes to the review helpfulness and ELM literature by identifying the impact on perceived helpfulness from a comprehensive perspective of consumer review and information consistency.
Distrust of banks among the unbanked and banked
Authors: Grable John , Kwak Eun Jin , Archuleta Kristy
Published: June 2023

Purpose

The purpose of this study was to explore the concept of distrust of traditional banking institutions as a factor that can explain the choice to remain unbanked in a marketplace that is designed to be financially inclusive.

Design/methodology/approach

Earning, spending, saving and borrowing data collected between May 2021 and February 2022 from 17,819 consumers living in the United States were used to examine the factors associated with distrust of banks. Using a conceptual framework borrowed from the health services profession, the study was conducted in two stages. At the first stage, distrust among the unbanked and banked was estimated using a Boruta-random forest algorithm. At the second stage of the analysis, a logit regression model was estimated to validate the variables identified in the Boruta-random forest analysis.

Findings

Results from the analyses show that distrust of banks is multi-layered where being older, believing the country is heading in the wrong direction and being less confident in one's ability to obtain a personal loan in the amount of $1 to $999 are important factors related to distrust of banks among the unbanked.

Research limitations/implications

This study shows how an ensemble machine learning technique based on a decision-tree methodology can be used to obtain unique insights into complicated data and large datasets within the bank marketing field.

Originality/value

The paper provides a discussion about ways domains of trust and specific variables can be utilized to address the persistent problem of financial exclusion in the United States. Implications for bankers, researchers, educators and policymakers are provided.