bluuebunny/crossref_metadata_2025 huggingface dataset:
Persistent Exertional Dyspnea and Perceived Exercise Intolerance After Mild COVID-19: A Critical Role for Breathing Dysregulation?
Authors: van Voorthuizen Esther L , van Helvoort Hanneke A C , Peters Jeanette B , van den Heuvel Michel M , van den Borst Bram
Published: July 2022

Objective

After mild COVID-19, a subgroup of patients reported post–acute-phase sequelae of COVID-19 (PASC) in which exertional dyspnea and perceived exercise intolerance were common. Underlying pathophysiological mechanisms remain incompletely understood. The purpose of this study was to examine outcomes from cardiopulmonary exercise testing (CPET) in these patients.

Methods

In this observational study, participants were patients who were referred for the analysis of PASC after mild COVID-19 and in whom CPET was performed after standard clinical workup turned out unremarkable. Cardiocirculatory, ventilatory, and metabolic responses to and breathing patterns during exercise at physiological limits were analyzed.

Results

Twenty-one patients (76% women; mean age = 40 years) who reported severe disability in physical functioning underwent CPET at 32 weeks (interquartile range = 22–52) after COVID-19. Mean peak O2 uptake was 99% of predicted with normal anaerobic thresholds. No cardiovascular or gas exchange abnormalities were detected. Twenty of the 21 patients (95%) demonstrated breathing dysregulation (ventilatory inefficiency [29%], abnormal course of breathing frequency and tidal volume [57%], absent increase of end-tidal Pco2 [57%], and abnormal resting blood gases [67%]).

Conclusion

Breathing dysregulation may explain exertional dyspnea and perceived exercise intolerance in patients with PASC after mild COVID-19 and can be present in the absence of deconditioning. This finding warrants further study on the levels of neural control of breathing and muscle function, and simultaneously provides a potential treatment opportunity.

Impact

This study contributes to the understanding of persistent exertional dyspnea and perceived exercise intolerance following mild COVID-19, which is vital for the development of effective rehabilitation strategies.
Factors associated with depression in residents in the post-epidemic era
Authors: Li S , Guo B , Yang Q , Yin J , Jiang Y , Tian L , Ji Y , Zhu H
Published: July 2022

Objective

To explore the factors associated with depression in residents in the post-epidemic era of COVID-19.

Methods

A multi-stage stratified random sampling method was used to conduct a questionnaire survey among community residents through self-designed questionnaires and self-rating depression scale (SDS). Multivariate logistic regression analysis was performed on the influencing factors of depressive symptoms.

Results

A total of 1993 residues completed the survey of depression status. The incidence of depressive symptoms was 27.04%. The multivariate logistic regression analysis showed that female (odds ratio (OR): 6.239, 95% confidence interval (CI): 2.743–10.698), body mass index (BMI) > 24 (OR: 2.684, 95% CI: 1.059–3.759) and drinking (OR: 1.730, 95% CI: 1.480–3.153) were the risk factors for developing depressive symptoms. Married (OR: 0.417, 95% CI: 0.240–0.652), monthly income (3001–5000 yuan, OR: 0.624, 95% CI: 0.280–0.756; >5000 yuan, OR: 0.348, 95% CI: 0.117–0.625), ordinary residents (OR: 0.722, 95% CI: 0.248–0.924) and urban residents (OR: 0.655, 95% CI: 0.394–0.829) were the protective factors of depressive symptoms.

Conclusions

Under the post-epidemic era of COVID-19, depressive symptoms are still common among community residents in China. Gender, BMI, drinking, marriage, monthly income and nature of personnel and residential area are associated with the incidence of depressive symptoms.
pyhiiextractor: a tool to detect and extract physical properties of H ii regions from integral field spectroscopic data
Authors: Lugo-Aranda A Z , Sánchez S F , Espinosa-Ponce C , López-Cobá C , Galbany L , Barrera-Ballesteros J K , Sánchez-Menguiano L , Anderson J P
Published: July 2022

We present a new code named pyhiiextractor, which detects and extracts the main features (positions and radii) of clumpy ionized regions, i.e. candidate H ii regions, using $\rm {H}\,\alpha$ emission line images. Our code is optimized to be used on the dataproducts provided by the pipe3d pipeline (or dataproducts with such a format), applied to high-spatial resolution integral field spectroscopy data (like that provided by the AMUSING++ compilation, using muse). The code provides the properties of both the underlying stellar population and the emission lines for each detected H ii candidate. Furthermore, the code delivers a novel estimation of the diffuse ionized gas (DIG) component, independent of its physical properties, which enables a decontamination of the properties of the H ii regions from the DIG. Using simulated data, mimicking the expected observations of spiral galaxies, we characterize pyhiiextractor and its ability to extract the main properties of the H ii regions (and the DIG), including the line fluxes, ratios, and equivalent widths. Finally, we compare our code with other such tools adopted in the literature, which have been developed or used for similar purposes: pyhiiexplorer, sourceextractor, hiiphot, and astrodendro. We conclude that pyhiiextractor exceeds the performance of previous tools in aspects such as the number of recovered regions and the distribution of sizes and fluxes (an improvement that is especially noticeable for the faintest and smallest regions). pyhiiextractor is therefore an optimal tool to detect candidate H ii regions, offering an accurate estimation of their properties and a good decontamination of the DIG component.
Consumer Search and Prices in the Automobile Market
Authors: Moraga-González José Luis , Sándor Zsolt , Wildenbeest Matthijs R
Published: July 2022

This article develops a discrete choice model of demand with optimal sequential consumer search. Consumers first choose a product to search; then, once they learn the utility they get from the searched product, they choose whether to buy it or to keep searching. We characterize the search problem as a standard discrete choice problem and propose a parametric search cost distribution that generates closed-form expressions for the probability of purchasing a product. We propose a method to estimate the model that supplements aggregate product data with individual-specific data which allows for the separate identification of search costs and preferences. We estimate the model using data from the automobile industry and find that search costs have non-trivial implications for elasticities and markups. We study the effects of exclusive dealing regulation and find that firms benefit at the expense of consumers, who face higher search costs and higher prices than would be the case if multi-brand dealerships were used.
Prevalence of non-coeliac gluten sensitivity and assessment of the response to gluten-free diet in a cohort of patients with fibromyalgia
Authors: Almirall Miriam , Casellas Francesc , Dot Joan , de Torres Inés , Segurola Hegoi , Marsal Sara
Published: July 2022

Objectives

To establish the prevalence of non-coeliac gluten sensitivity (NCGS) in a cohort of fibromyalgia patients and to evaluate their clinical response to a six-week gluten-free diet (GFD), the improvement in their symptoms, the percentage of diet responders who did not fulfil the diagnostic criteria for NCGS and the baseline characteristics that were associated with diet response and diagnostic criteria fulfilment.

Methods

Uncontrolled prospective experimental study in a cohort of patients with fibromyalgia from a specialized hospital unit. The percentage of patients that fulfilled the Salerno Experts’ Criteria, that responded to GFD, that improved their symptomatology and baseline characteristics associated with GFD response and diagnostic criteria fulfilment was analysed.

Results

In total, 142 patients were selected and a NCGS prevalence of 5.6% was observed. A total of 21.8% responded to GFD due to their improvement in intestinal symptoms. In total, 74.2% of the responders did not fulfil the Salerno Experts’ Criteria. The presence of diarrhoea and intraepithelial lymphocytosis and lower levels of anxiety were predictive factors of GFD response. No predictive factors of NCGS criteria fulfilment were found due to the low number of discriminators between gluten and placebo.

Conclusions

A NCGS prevalence similar to that estimated in the general population was found. A GFD cannot be systematically recommended to all patients with fibromyalgia, although it could be evaluated in those with diarrhoea or intraepithelial lymphocytosis to evaluate if there are improvements in their intestinal symptoms.
Maternal Schizophrenia and the Risk of a Childhood Chronic Condition
Authors: Vigod Simone N , Ray Joel G , Cohen Eyal , Wilton Andrew S , Saunders Natasha R , Barker Lucy C , Berard Anick , Dennis Cindy-Lee , Holloway Alison C , Morrison Katherine , Oberlander Tim F , Hanley Gillian , Tu Karen , Brown Hilary K
Published: July 2022

Background and Hypothesis

Maternal schizophrenia heightens the risk for certain perinatal complications, yet it is not known to what degree future childhood chronic health conditions (Childhood-CC) might arise.

Study Design

This population-based cohort study using health administrative data from Ontario, Canada (1995–2018) compared 5066 children of mothers with schizophrenia to 25 324 children of mothers without schizophrenia, propensity-matched on birth-year, maternal age, parity, immigrant status, income, region of residence, and maternal medical and psychiatric conditions other than schizophrenia. Cox proportional hazard models generated hazard ratios (HR) and 95% confidence intervals (CI) for incident Childhood-CCs, and all-cause mortality, up to age 19 years.

Study Results

Six hundred and fifty-six children exposed to maternal schizophrenia developed a Childhood-CC (20.5/1000 person-years) vs. 2872 unexposed children (17.1/1000 person-years)—an HR of 1.18, 95% CI 1.08–1.28. Corresponding rates were 3.3 vs. 1.9/1000 person-years (1.77, 1.44–2.18) for mental health Childhood-CC, and 18.0 vs. 15.7/1000 person-years (1.13, 1.04–1.24) for non-mental health Childhood-CC. All-cause mortality rates were 1.2 vs. 0.8/1000 person-years (1.34, 0.96–1.89). Risk for children exposed to maternal schizophrenia was similar whether or not children were discharged to social service care. From age 1 year, risk was greater for children whose mothers were diagnosed with schizophrenia prior to pregnancy than for children whose mothers were diagnosed with schizophrenia postnatally.

Conclusions

A child exposed to maternal schizophrenia is at elevated risk of chronic health conditions including mental and physical subtypes. Future research should examine what explains the increased risk particularly for physical health conditions, and what preventive and treatment efforts are needed for these children.
Social Workers as Information Navigators: Insights into the Use of the Web for Serving Clients
Authors: Lee Wonhyung , Lee Eunwoo
Published: July 2022

Social workers’ critical role as service navigators on behalf of their clients is expanding in the online space at a faster pace than ever before. This study examined the process and outcome of online information navigation through the lens of service providers and service users based on observational and interactive surveys. T tests and correlation results showed that human services providers demonstrated a higher capacity to visit more websites and yield more accurate search outcomes in a similar duration of time compared with general service users. Results suggest that digital literacy for navigating information online can be improved through educational opportunities. At the same time, both groups shared some common feedback on desired features for future service navigation online, including but not limited to an open search bar, search filters, instruction videos, live chat, and discussion forums for seeking mutual help and networking. The findings bear implications for formulating the roles, responsibilities, and desired competencies of social workers for online service navigation in the digital and postpandemic future.
Grasping criteria for success: engaging undergraduate students in formative feedback by means of digital peer workshops
Authors: Albano Giovannina , Pierri Anna , Sabena Cristina
Published: July 2022

In our study we exploit digital tools in order to foster a relational approach to mathematics undergraduate students. Specifically, we designed formative assessment workshops based on peer feedback, with the aim to promote self-assessment and reflection on one’s own mathematical activity. In the paper we describe the design of an educational activity and investigate how the students perceived their experience with the designed formative assessment workshops. Furthermore, we provide evidence of the effectiveness of the designed workshops in terms of aligning students’ feedback with the teacher’s criteria.
9New Materialisms
Authors: Diener Samuel
Published: July 2022

The works reviewed in this year’s essay on the New Materialisms raise questions about the field’s orientation to knowledge creation and to its subjects of study, critiquing universalizing discussions of the Anthropocene, questioning notions of ‘pure’ or ‘pristine’ Nature, and proposing considerations for ethical and scholarly attention. Along the way, they touch on the problems of human ontology, employ the New Materialisms as a method for scholarship across the disciplines and for applied scholarly and creative work, raise the question of the New Materialisms’ political stakes (or lack thereof), and attempt to negotiate relationships between Western academic knowledge-making and other forms and situations of knowledge. Following an overview of these questions in the introduction, the essay is divided into four sections: 1. Utopia Now, focusing on Jayna Brown’s Black Utopias: Speculative Life and the Music of Other Worlds; 2. Clutter Culture, which discusses Rebecca R. Falkoff’s Possessed: A Cultural History of Hoarding; 3. National Dirt, on Mieka Erley’s On Russian Soil: Myth and Materiality; and 4. Cartographies of the Anthropocene, which considers Anna L Tsing, Jennifer Deger, Alder Keleman Saxena, and Feifei Zhou’s multimedia online project Feral Atlas: The More-Than-Human Anthropocene.
Efficacy and safety of hybutimibe on primary hypercholesterolemia: a randomized, double-blinded, placebo and positive–controlled, parallel phase II study
Authors: Qi Litong , Zhao Shuiping , Chen Jiyan , Zhang Mei , Li Xiaodong , Dong Yugang , Guo Xiaomei , Huang Kai , Wang Fang , Huo Yong , Ge Junbo
Published: July 2022

Background and purpose:

Hybutimibe is proved to be safe in healthy adults by a phase I study. A multi-center, randomized, double-blind phase II clinical trial evaluated its effectiveness and safety of Hybutimibe in the treatment of primary hypercholesterolemia.

Methods:

A total of 244 patients between August 2014 and August 2015, with primary hypercholesterolemia from 15 centers in China were enrolled and randomly assigned to receive placebo, ezetimibe, or hybutimibe 5, 10, or 20 mg/day in a 1:1:1:1:1 ratio. The primary outcome was evaluated from the change rate of low-density lipoprotein cholesterol (LDL-C) at week 8 from baseline, whereas secondary outcomes were evaluated from the change rates of LDL-C, TC, TG, HDL-C, non-HDL-C, APO-B, APO-A1 at weeks 1, 2, 4, and 8 from baseline.

Results:

After 8 weeks of treatment, the average decrease rate of LDL-C was −20.01% for ezetimibe, −10.84% (95% CI: −14.67, −7.00) for hybutimibe 5 mg/day, −17.06% (95% CI: −20.83, −13.29) for hybutimibe 10 mg/day, and −17.04% (95% CI: −20.30, −13.79) for hybutimibe 20 mg/day, respectively. The change rates of TC, non-HDL-C, and APO-B levels were significantly improved in all treatments compared with placebo (P < 0.05), whereas changes in the above lipid profiles of hybutimibe 20 mg/day were similar with ezetimibe. In terms of safety, the most common adverse events were elevation in ALT, gastrointestinal reaction, dizziness, and headache.

Conclusions:

This clinical study found that hybutimibe with the least dose of 5 mg/day effectively improved the LDL-C, TC, non-HDL-C, and APO-B levels in patients with primary hyperlipidemia with good tolerance and safety with no significant effect on TG levels.
Urinary Biomarkers of Polycyclic Aromatic Hydrocarbons and Timing of Pubertal Development: The California PAH Study
Authors: John Esther M. , Keegan Theresa H. , Terry Mary Beth , Koo Jocelyn , Ingles Sue A. , Nguyen Jenny T. , Thomsen Catherine , Santella Regina M. , Nguyen Khue , Yan Beizhan
Published: July 2022

Background:

Polycyclic aromatic hydrocarbons (PAHs) are endocrine-disrupting chemicals. Few studies have evaluated the association between pubertal development in girls and PAH exposures quantified by urinary biomarkers.

Methods:

We examined associations of urinary PAH metabolites with pubertal development in 358 girls 6–16 years of age from the San Francisco Bay Area enrolled in a prospective cohort from 2011 to 2013 and followed until 2020. Using baseline data, we assessed associations of urinary PAH metabolites with pubertal development stage. In prospective analyses limited to girls who at baseline had not yet started breast (N = 176) or pubic hair (N = 179) development or menstruation (N = 267), we used multivariable Cox proportional hazards regression to assess associations of urinary PAH metabolites with the onset of breast and pubic hair development, menstruation, and pubertal tempo (interval between the onset of breast development and menstruation).

Results:

We detected PAH metabolites in >98% of girls. In cross-sectional analyses using baseline data, PAH metabolites were not associated with the pubertal development stage. In prospective analyses, higher concentrations (≥ median) of some PAH metabolites were associated with two-fold higher odds of earlier breast development (2-hydroxy naphthalene, 1-hydroxy phenanthrene, summed hydroxy phenanthrenes) or pubic hair development (1-hydroxy naphthalene) among girls overweight at baseline (body mass index-for-age percentile ≥85) compared with nonoverweight girls with lower metabolites concentrations. PAH metabolites were not associated with age at menarche or pubertal tempo.

Conclusions:

PAH exposures were widespread in our sample. Our results support the hypothesis that, in overweight girls, PAHs impact the timing of pubertal development, an important risk factor for breast cancer.
Esaxerenone Blocks Vascular Endothelial Inflammation Through SGK1
Authors: Yamamoto Hiroyasu , Yoshida Nao , Kihara Shinji
Published: July 2022

Chronic low-grade inflammation and excess mineralocorticoid receptor (MR) activation are well-known pathological conditions of metabolic syndrome (MetS). To elucidate the crosstalk between inflammation and MR signaling, we focused on serum/glucocorticoid-regulated kinase 1 (SGK1) in vascular endothelial cells. We treated human aortic endothelial cells (HAECs) with esaxerenone (ESX), a novel nonsteroidal highly selective MR antagonist, or spironolactone (SPL), a classic competitive MR antagonist, followed by stimulation with tumor necrosis factor (TNF)-α. ESX at therapeutic concentrations attenuated the long-term induction of TNF-α–stimulated inflammatory molecules in HAEC, whereas SPL had only a minor effect at 10 μM. We found long-term TNF-α–stimulated induction of SGK1 mRNA and protein levels in HAEC and that ESX pretreatment significantly decreased SGK1 mRNA and protein levels at both the basal and the TNF-α–stimulated conditions, whereas SPL had no effect on SGK1 mRNA and protein levels. In addition, the TNF-α–induced nuclear factor kappa-light-chain-enhancer of activated B cell activity was suppressed by the treatment with ESX, and it was abrogated by SGK1 overexpression. These results indicated that ESX has direct anti-inflammatory effects in HAEC via the blocking of long-term TNF-α–induced SGK1 activation and that SGK1 could be a key molecule linking cytokine-induced vascular chronic inflammation and MR activation.
Barriers to surgical menopause counseling in gynecologic cancers: a quantitative and qualitative study of patients and providers
Authors: Wang Connor C. , Huang Dandi S. , Carlson Anisa M. , Li Zhanhai , Al-Niaimi Ahmed , Williams Makeba
Published: July 2022

Objective

The objective of this study is to identify factors associated with receiving surgical menopause counseling in gynecologic cancer patients, as well as patient and provider perspectives, regarding surgical menopause counseling and management.

Methods

We conducted a single-institution mixed-method study combining retrospective chart review and patient and provider surveys. Patients younger than 51 years who experienced surgical menopause after gynecologic cancer treatment from January 2017 to December 2019 were surveyed in April 2021 about experiences with menopause counseling, barriers to care, and quality of life. We then reviewed charts of only patients who fully completed surveys. All gynecologic oncology providers were surveyed about surgical menopause practices. Logistic regression identified factors associated with receiving counseling.

Results

Sixty-six of 75 identified met inclusion criteria and received survey invitations. Thirty-five (53%) completed surveys. Sixty percent had documented surgical menopause counseling. Patients who were counseled were younger (43 vs 48.5 years, P = 0.005), more likely to have referrals for menopause care (12 vs 9, P = 0.036), more likely to have menopause providers other than oncology providers (14 vs 8, P = 0.001), and had fewer comorbidities. Decreasing age at surgery increased odds of counseling. Most reported continued menopause symptoms and quality of life disturbances. Half were satisfied with menopause care. Majority preferred counseling from oncology providers. Most providers always counseled on surgical menopause but cited lack of time as the primary obstacle for complete counseling.

Conclusions

Younger age at surgery increased odds of receiving surgical menopause counseling. Gynecologic cancer patients experienced significant menopause-related disturbances. Improved understanding of patient and provider preferences and greater emphases on surgical menopause and survivorship will improve care for gynecologic oncology patients.
Evaluating the Quality and Reliability of Gender-affirming Surgery Videos on YouTube and TikTok
Authors: Song Siyou , Park Keon Min , Phong Kiet , Kim Esther A.
Published: July 2022

Background:

Social media platforms have changed the way medical information is disseminated. Transgender patients may utilize social media to learn about gender-affirming surgery (GAS). Although videos on social media are readily accessible, their content is not verified or peer-reviewed. Therefore, this study aimed to evaluate the quality and reliability of YouTube and TikTok videos related to GAS.

Methods:

YouTube and TikTok were queried for gender-affirming top surgery, metoidioplasty, phalloplasty, breast augmentation, and vaginoplasty. Quality of video content was analyzed by the DISCERN scale. Quality scores were compared among the type of GAS, account user, and content category.

Results:

There were 275 YouTube videos and 55 TikTok videos. Most videos focused on masculinizing top surgery (P < 0.001). Overall, videos on masculinizing GAS had higher quality and reliability than videos on feminizing GAS (P < 0.001). Chest surgery videos were of higher quality than those on genital surgery (P ≤ 0.001). Videos on masculinizing top surgery had the highest quality, whereas vaginoplasty had the lowest quality and reliability (P < 0.001). Videos produced by health care professionals and academic institutions had the greatest quality and reliability, respectively (P < 0.0001), whereas videos produced by patients were the least reliable (P < 0.0001).

Conclusions:

Videos on GAS ranged from poor to good quality and reliability. Health care professionals, especially plastic surgeons, should create high-quality videos on social media to educate transgender patients. There should also be greater efforts in disseminating existing high-quality videos on social media. Resources posted on social media platforms can reach a wide audience through accessible means.
Safety and Feasibility of Infliximab Therapy in Children With Kawasaki Disease Who Received Live Vaccinations
Authors: Ohnishi Yuji , Okada Seigo , Kawakami-Miyake Akiko , Furuta Takashi , Fukano Reiji , Yasudo Hiroki , Shimokawa Mototsugu , Hasegawa Shunji
Published: July 2022

Background:

Kawasaki disease (KD) is an acute and febrile systemic vasculitis that occurs during childhood. Infliximab (IFX) is a chimeric monoclonal antibody that binds to tumor necrosis factor-α. Although IFX therapy is a useful option for refractory KD, vaccine-associated infections may develop after therapy. In Japan, IFX therapy is recommended after a duration of at least 3 months after live vaccinations or at least 6 months after Bacillus Calmette-Guérin (BCG) in children with KD. However, the appropriate duration between live vaccinations and IFX therapy is unclear.

Methods:

We investigated children who developed KD within 3 months after live vaccinations or within 6 months after BCG. Clinical characteristics, side effects of therapies and efficacy of live vaccinations were retrospectively investigated.

Results:

Forty-eight patients developed KD within 3 months of live vaccinations or within 6 months after BCG. Eight patients underwent IFX therapy. There were no apparent vaccine-associated infections. The patients who underwent IFX acquired protective IgG antibody titers in the 5 of 6 live vaccines.

Conclusions:

Safe and appropriate duration between live vaccinations and IFX therapy for KD patients could be shorter in the future, although more studies are warranted to establish the safe duration.
Health‐Related Quality of Life in Pediatric Inflammatory Bowel Disease During COVID‐19 Pandemic
Authors: Fedele Flora , Martinelli Massimo , Strisciuglio Caterina , Dolce Pasquale , Giugliano Francesca Paola , Scarpato Elena , Staiano Annamaria , Miele Erasmo
Published: July 2022

Objectives:

The aims of our study were to evaluate health‐related quality of life (HRQoL) in children affected by inflammatory bowel disease (IBD) during the first wave of Coronavirus disease 2019 (COVID‐19) pandemic and after 12 months.

Methods:

This was a single‐center, prospective, observational study conducted between April 2020 and April 2021. Children from 10 to 18 years with a confirmed diagnosis of IBD were enrolled during the first COVID‐19–related national quarantine. The following information was collected at the baseline and after 12 months: IBD subtype, location and phenotype, disease activity, current and previous therapies. Patients were asked to complete the PROMIS Anxiety and IMPACT III questionnaires.

Results:

One hundred and eighteen patients were enrolled, of whom 54 (46%) were affected by Crohn disease (CD) and 64 (54%) with ulcerative colitis (UC; median age: 15.5 years, range 10.3–18; M/F: 68/50). Median HRQoL was significantly decreased after 12 months compared with the beginning of COVID‐19–related quarantine (T1: 76.7 vs T2: 72.8; P < 0.001). At 12 months, a higher number of children were reported to be in active disease when compared with the enrollment [T2: 22/108 (20.4%) vs T1: 12/118 (10%); P = 0.02]. Multivariate analysis showed a significant influence on HRQoL of quarantine period (P < 0.001), female sex (P = 0.016), biologic therapy (P = 0.011), and active disease (P < 0.001).

Conclusions:

A deterioration of HRQoL after 12 months from COVID‐19–related quarantine was observed. Additionally, the higher number of children with active disease at 12 months compared with enrollment may suggest detrimental consequences of the reduced disease control, contributing to decreased HRQoL.
Intensive Outpatient Treatment of Pediatric Rumination Syndrome in the Era of Telemedicine
Authors: Hawa Kathryn , Lu Peter L. , Holzmacher Meghan , Wall Jody , Bali Neetu , Vaz Karla , Yacob Desale , Di Lorenzo Carlo , Van Diest Ashley Kroon
Published: July 2022

Objectives:

We have had success treating children with severe rumination syndrome using a multidisciplinary intensive outpatient program (IOP) involving multiple treatment sessions daily. During the coronavirus disease 2019 (COVID‐19) pandemic, we temporarily transitioned care to telemedicine. The objective of this study is to compare outcomes of patients with rumination syndrome who completed IOP treatment in person versus by telemedicine.

Methods:

We performed a retrospective review of patients diagnosed with rumination syndrome who participated in IOP treatment from 2018 to 2020. Similar treatment sessions were performed involving medical and behavioral techniques provided by a multidisciplinary team during telemedicine visits. Families/patients were asked to complete a survey outlining their child’s current rumination symptom severity and review the IOP.

Results:

We included 34 patients (79% F, median age 15 years, range 7–19 years) who completed IOP treatment. Twenty‐six patients (76%) were treated in person and 8 patients (24%) by telemedicine. For patients treated in person, 76% (19/25) had improvement in symptoms while 16% (4/25) had complete resolution of symptoms. For patients treated by telemedicine, 88% (7/8) had improvement in their symptoms. There were no significant differences between groups in likelihood of improvement. Overall, 78% (18/23) preferred in person therapy while 17% (4/23) did not have a preference. All 18 of the in‐person cohort who completed follow‐up surveys preferred in‐person management.

Conclusions:

Multidisciplinary intensive outpatient treatment for children and adolescents with severe rumination syndrome is effective. Although telemedicine may be an alternative to in person therapy, majority of families prefer in person visits.
Titers and capacity of neutralizing antibodies against SARS-CoV-2 variants after heterologous booster vaccination in health care workers primed with two doses of ChAdOx1 nCov-19: a single-blinded, randomized clinical trial
Authors: Chuang Chih-Hsien , Huang Chung-Guei , Huang Ching-Tai , Chen Yi-Ching , Kung Yu-An , Chen Chih-Jung , Chuang Tzu-Chun , Liu Ching-Chi , Huang Po-Wei , Yang Shu-Li , Gu Po-Wen , Shih Shin-Ru , Chiu Cheng-Hsun
Published: July 2022

Background

Booster vaccination is important because of waning immunity and variant immune evasion. We conducted a single-blinded, randomized trial to evaluate the safety, reactogenicity, and immunogenicity of heterologous booster vaccination in health care workers (HCW) who had received two doses of ChAdOx1 nCov-19.

Methods and findings

HCW at least 90 days after the second dose were enrolled to receive one of the four vaccines: BNT162b2, half-dose mRNA-1273, mRNA-1273, and MVC-COV1901. The primary outcomes were humoral and cellular immunogenicity and the secondary outcomes safety and reactogenicity 28 days post-booster. 340 HCW were enrolled: 83 received BNT162b2 (2 excluded), 85 half-dose mRNA-1273, 85 mRNA-1273, and 85 MVC-COV1901. mRNA vaccines had more reactogenicity than protein vaccine.

Anti-spike IgG increased by a fold of 8.4 for MCV-COV1901, 32.2 for BNT162b2, 47.6 for half-dose mRNA-1273 and 63.2 for mRNA1273. The live virus microneutralization assay (LVMNA) against the wild type, alpha and delta variants were consistent with anti-spike IgG for all booster vaccines. The LVMNA in the four groups against omicron variant were 6.4 to 13.5 times lower than those against the wild type. Serum neutralizing antibody against omicron variant was undetectable in 60% of the participants who received MCV-COV1901 as a booster by LVMNA. By using pseudovirus neutralizing assay, we found that neutralization activity in the four groups against omicron variant were 4.6 to 5.2 times lower than that against the D614G. All booster vaccines induced comparable T cell response.

Conclusions

Third dose booster not only increases neutralizing antibody titer but also enhances antibody capacity against SARS-CoV-2 variants. mRNA vaccines are preferred booster vaccines for those after primary series of ChAdOx1 nCov-19.

Trial registration

ClinicalTrials.govNCT05132855
Virtual wards: A rapid evidence synthesis and implications for the care of older people
Authors: Norman Gill , Bennett Paula , Vardy Emma R.L.C.
Published: July 2022

Virtual wards are an area of rapid development within the National Health Service in the UK, and frailty has been selected as one of the first clinical pathways to be developed. This is in the context of existing longstanding hospital at home services in some areas. A rapid evidence synthesis was completed to guide the local healthcare system in the North West of England. This is a rapid approach to synthesising existing research which focuses on existing evidence synthesis where possible. Questions were addressed on clinical-effectivness, cost-effectiveness, barriers and facilitators, models of care and use in practice, and staff and patient and carer experience. We found that whilst there was a significant evidence base for hospital at home, there was less evidence for virtual wards. There is lack of guidance for key aspects of virtual wards including team characteristics, outcome selection and data protection. We recommend that research and evaluation is integrated into development of virtual ward models of care. Of particular relevance for older people cared for on virtual wards is the issue of carer strain, an area which may be frequently overlooked.
The Art of Pain: A Quantitative Colour Analysis of the Self-Portraits of Frida Kahlo
Authors: Turkheimer Federico E. , Liu Jingyi , Fagerholm Erik D. , Dazzan Paola , Loggia Marco L. , Bettelheim Eric
Published: July 2022

Frida Kahlo (1907-1954) was a Mexican artist who is remembered for her self-portraits, pain and passion, and bold, vibrant colours. This work aims to use her life story and her artistic production in a longitudinal study to examine with quantitative tools the effects of physical and emotional pain (rage) on artistic expression.

Kahlo suffered from polio as a child, was involved in a bus accident as a teenager where she suffered multiple fractures of her spine and had 30 operations throughout her lifetime. She also had a tempestuous relationship with her painter husband, Diego Rivera. Her physical and personal troubles however became the texture of her vivid visual vocabulary — usually expressed through the depiction of Mexican and indigenous culture or the female experience and form.

We applied colour analysis to a series of Frida’s self-portraits and revealed a very strong association of physical pain and emotional rage with low wavelength colours (red and yellow), indicating that the expression of her ailments was, consciously or not, achieved by increasing the perceived luminance of the canvas. Further quantitative analysis that used the fractal dimension identified “The broken column” as the portrait with higher compositional complexity, which matches previous critical acclaim of this portrait as the climax of her art. These results confirm the ability of colour analysis to extract emotional and cognitive features from artistic work. We suggest that these tools could be used as markers to support artistic and creative interventions in mental health.
Integrating Isoniazid Preventive Therapy into the Fast-Track HIV Treatment Model in Urban Zambia: A Proof-of -Concept Pilot Project
Authors: Mukumbwa-Mwenechanya Mpande , Mubiana Muhau , Somwe Paul , Zyambo Khozya , Simwenda Maureen , Zongwe Nancy , Kalunkumya Estella , Mwango Linah Kampilimba , Rabkin Miriam , Mpesela Felton , Chungu Fred , Mwanza Felix , Preko Peter , Bolton-Moore Carolyn , Bosomprah Samuel , Sharma Anjali , Morton Khunga , Kasonde Prisca , Mulenga Lloyd , Lingu Patrick , Mulenga Priscilla Lumano
Published: July 2022

Introduction

Most people living with HIV (PLHIV) who are established on treatment in Zambia receive multi-month prescribing and dispensing (MMSD) of antiretroviral therapy (ART) and are enrolled in less-intensive differentiated service delivery (DSD) models, such as Fast Track (FT), in which clients pick up ART every 3-6 months and make clinical visits to health facilities every 6 months. In 2019, Zambia introduced Isoniazid Preventive Therapy (IPT) with scheduled visits at 2 weeks and 1, 3, and 6 months. The asynchronous IPT and HIV appointment schedules were inconvenient and not client centered. In response, we piloted integrated MMSD/IPT in the FT HIV treatment model.

Methods

We implemented and evaluated a proof-of-concept pilot project at one purposively selected high-volume facility in Lusaka, Zambia between July 2019 and May 2020. We sensitized stakeholders, adapted training materials and standard operating procedures, and screened adults in FT for TB as per national guidelines. Participants received structured TB/IPT education, a 6-month supply of isoniazid and ART, an aligned 6th month IPT/MMSD clinic appointment, and phone appointments at 2 weeks and months 1-5 following IPT initiation. We used descriptive statistics to characterize IPT completion rates, phone appointment keeping, side effect frequency and Fisher’s exact test to determine if these varied by participant characteristics. Notes from monthly meetings and discussions were used to synthesize key lessons learned.

Results

1,167 clients were screened for eligibility and 818 (70.1%) were enrolled. Two thirds (66%) were female, median age was 42 years, and 56.6% had been on ART for ≥ 5 years. 738 (90.2%) completed a 6-month course of IPT and 66 (8.1%) reported IPT-related side effects. 539 clients (65.9%) attended all 7 telephone appointments. There were no significant differences in these outcomes by age, sex, or time on ART. Lessons learnt include the value of promoting project ownership, client empowerment, securing supply chain, adapting existing processes, and cultivating a collaborative structured learning environment.

Conclusions

Integrating multi-month dispensing and telephone follow up of IPT into the FT HIV treatment model is a promising approach to scaling-up TB preventive treatment among PLHIV, although limited by barriers to consistent phone access.
MetaGeneMark-2: Improved Gene Prediction in Metagenomes
Authors: Gemayel Karl , Lomsadze Alexandre , Borodovsky Mark
Published: July 2022

Accurate prediction of protein-coding genes in metagenomic contigs presents a well-known challenge. Particularly difficult is to identify short and incomplete genes as well as positions of translation initiation sites. It is frequently assumed that initiation of translation in prokaryotes is controlled by a ribosome binding site (RBS), a sequence with the Shine-Dalgarno (SD) consensus situated in the 5’ UTR. However, ∼30% of the 5,007 genomes, representing the RefSeq collection of prokaryotic genomes, have either non-SD RBS sequences or no RBS site due to physical absence of the 5’ UTR (the case of leaderless transcription). Predictions of the gene 3’ ends are much more accurate; still, errors could occur due to the use of incorrect genetic code. Hence, an effective gene finding algorithm would identify true genetic code in a process of the sequence analysis. In this work prediction of gene starts was improved by inferring the GC content dependent generating functions for RBS sequences as well as for promoter sequences involved in leaderless transcription. An additional feature of the algorithm was the ability to identify alternative genetic code defined by a reassignment of the TGA stop codon (the only stop codon reassignment type known in prokaryotes). It was demonstrated that MetaGeneMark-2 made more accurate gene predictions in metagenomic sequences than several existing state-of-the-art tools.
Leptospira interrogans prevents macrophage cell death and pyroptotic IL1β release through its atypical lipopolysaccharide
Authors: Bonhomme Delphine , Hernandez-Trejo Veronica , Papadopoulos Stylianos , Pigache Rémi , d’Andon Martine Fanton , Outlioua Ahmed , Boneca Ivo G. , Werts Catherine
Published: July 2022

Leptospira interrogans are bacteria that can infect all vertebrates and are responsible for leptospirosis, a neglected zoonosis. Some hosts are susceptible to leptospirosis whereas mice are resistant and get chronically colonized. Although leptospires escape recognition by some immune receptors, they activate NLRP3-inflammasome and trigger IL1β secretion. Classically, IL1β secretion is associated with lytic inflammatory cell death called pyroptosis, resulting from cytosolic LPS binding to inflammatory caspases. Interestingly, we showed that L. interrogans do not trigger cell death in either murine, human, hamster, or bovine macrophages, escaping both pyroptosis and apoptosis. Strikingly, we also revealed in murine cells, a potent antagonistic effect of leptospires and their atypical LPS on spontaneous and E. coli LPS-induced cell death. The leptospiral LPS efficiently prevents caspase 11 dimerization and subsequent gasdermin D cleavage. Finally, we showed that pyroptosis escape by leptospires prevents massive IL1 β release, and we consistently found no major role of IL1-Receptor in controlling experimental leptospirosis in vivo. Overall, our findings described a novel mechanism by which leptospires dampen inflammation, thus potentially contributing to their stealthiness.

Graphical abstract
Inference of cell type-specific gene regulatory networks on cell lineages from single cell omic datasets
Authors: Zhang Shilu , Pyne Saptarshi , Pietrzak Stefan , Halberg Spencer , McCalla Sunnie Grace , Siahpirani Alireza Fotuhi , Sridharan Rupa , Roy Sushmita
Published: July 2022

Cell type-specific gene expression patterns are outputs of transcriptional gene regulatory networks (GRNs) that connect transcription factors and signaling proteins to target genes. Single-cell technologies such as single cell RNA-sequencing (scRNA-seq) and single cell Assay for Transposase-Accessible Chromatin using sequencing (scATAC-seq), can examine cell-type specific gene regulation at unprecedented detail. However, current approaches to infer cell type-specific GRNs are limited in their ability to integrate scRNA-seq and scATAC-seq measurements and to model network dynamics on a cell lineage. To address this challenge, we have developed single-cell Multi-Task Network Inference (scMTNI), a multi-task learning framework to infer the GRN for each cell type on a lineage from scRNA-seq and scATAC-seq data. Using simulated and real datasets, we show that scMTNI is a broadly applicable framework for linear and branching lineages that accurately infers GRN dynamics and identifies key regulators of fate transitions for diverse processes such as cellular reprogramming and differentiation.
Partitioned Local Depth analysis of time course transcriptomic data reveals elaborate community structure
Authors: Khoury Maleana , Berenhaut Kenneth , Moore Katherine , Allen Edward , Harkey Alexandria , Muhlemann Joëlle K. , Craven Courtney , Xu Jiayi , Jain Suchi , John David , Norris James , Muday Gloria K.
Published: July 2022

Transcriptome studies that provide temporal information are valuable for identifying groups of similarly-behaving transcripts, giving insight into overarching gene regulatory networks. Nevertheless, inferring transcriptional networks from time series data is challenging, in part because it is difficult to holistically consider both local relationships and global structure of these complex and overlapping transcriptional responses. To address this need, we employed the Partitioned Local Depth (PaLD) method to examine four time series transcriptomic datasets generated using the model plant Arabidopsis thaliana. Here, we provide a self-contained description of the method and demonstrate how it can be used to make predictions about gene regulatory networks based on time series data. The analysis provides a global network representation of the data from which graph partitioning methods and neighborhood analysis can reveal smaller, more well-defined groups of like-responding transcripts. These groups of transcripts that change in response to hormone treatment (e.g., auxin or ethylene) or high salinity were demonstrated to be enriched in common biological function and/or binding of transcription factors that were not identified with prior analyses of this data using other clustering and inference methodologies. These results reveal the ability of PaLD to generate predictions about gene regulatory networks using time series transcriptomic data, which can be of value to the systems biology community.
Coevolution-based prediction of key allosteric residues for protein function regulation
Authors: Xie Juan , Zhang Weilin , Zhu Xiaolei , Deng Minghua , Lai Luhua
Published: July 2022

Allostery is fundamental to many biological processes. Due to the distant regulation nature, how allosteric mutations, modifications and effector binding impact protein function is difficult to forecast. In protein engineering, remote mutations cannot be rationally designed without large scale experimental screen. Allosteric drugs have raised much attention due to their high specificity and possibility of overcoming existing drug-resistant mutations. However, optimization of allosteric compounds remains challenging. Here, we developed a novel computational method KeyAlloSite to predict allosteric site and to identify key allosteric residues (allo-residues) based on the evolutionary coupling model. We found that protein allosteric sites are strongly coupled to orthosteric site compared to non-functional sites. We further inferred key allo-residues by pairwise comparing the difference of evolutionary coupling scores of each residue in the allosteric pocket with the functional site. Our predicted key allo-residues are in accordance with previous experimental studies for typical allosteric proteins like BCR-ABL1, Tar and PDZ3, as well as key cancer mutations. We also showed that KeyAlloSite can be used to predict key allosteric residues distant from the catalytic site that are important for enzyme catalysis. Our study demonstrates that weak coevolutionary couplings contain important information of protein allosteric regulation function. KeyAlloSite can be applied in studying the evolution of protein allosteric regulation, designing and optimizing allosteric drugs, performing functional protein design and enzyme engineering.
LLPSWise - fast and accurate prediction of LLPS constituents
Authors: Pu Mengchen , Fu Biao , Zhang Yingsheng J.
Published: July 2022

The recent discovery of different types of biological liquid-liquid phase separation (LLPS) systems presents enormous opportunities to uncover underlying biological mechanisms from a single-molecule level to mesoscopic scales and beyond. While progress has been made on the front of computational prediction of LLPS propensity of proteins, the constituent identification of LLPS systems continues to be a pertinent issue that has yet to be addressed. Compiled evidence indicates that the biological mechanism of LLPS involves the employment of different biomolecules into their liquid-liquid separation phase. Since constituent identification relies on experimental approaches, the process is arduous and inefficient. Here, we propose a sequence based LLPS propensity prediction method and scan the human proteome and biochemical pathways to establish a systematic biological view of LLPS. Additionally, we present a fast, accurate method for identifying the constituents of LLPS systems. The source code for our method is available via https://github.com/promethiume/LLPSWise