bluuebunny/crossref_metadata_2025 huggingface dataset:
Quenching star formation with low-luminosity AGN winds
Authors: Almeida Ivan , Nemmen Rodrigo , Riffel Rogemar A
Published: September 2023

We present a simple model for low-luminosity active galactic nucleus (LLAGN) feedback through winds produced by a hot accretion flow. The wind carries considerable energy and deposits it on the host galaxy at kiloparsec scales and beyond, heating the galactic gas and thereby quenching star formation. Our model predicts that the typical LLAGN can quench more than 10 per cent of star formation in its host galaxy. We find that long-lived LLAGN winds from supermassive black holes (SMBHs) with masses ≥108 M⊙ and mass accretion rates $\dot{M} \gt 10^{-3} \dot{M}_{\rm Edd}\ (0.002\,{\rm M}_{\odot }\,\mathrm{ yr}^{-1})$ can prevent gas collapse and significantly quench galactic star formation compared to a scenario without AGNs, if the wind persists over 1 Myr. For sustained wind production over time-scales of 10 Myr or longer, SMBHs with 108 M⊙ or larger masses have important feedback effects with $\dot{M} \gt 10^{-4} \dot{M}_{\rm Edd}\ (0.0002\,{\rm M}_{\odot }\, \mathrm{ yr}^{-1})$.
Doppler confirmation of TESS planet candidate TOI−1408.01: grazing transit and likely eccentric orbit
Authors: Galazutdinov G A , Baluev R V , Valyavin G , Aitov V , Gadelshin D , Valeev A , Sendzikas E , Sokov E , Mitiani G , Burlakova T , Yakunin I , Antonyuk K A , Vlasyuk V , Romanyuk I , Rzaev A , Yushkin M , Ivanova A , Tavrov A , Korablev O
Published: September 2023

We report an independent Doppler confirmation of the TESS planet candidate orbiting an F-type main-sequence star TOI−1408 located 140 pc away. We present a set of radial velocities obtained with a high-resolution fibre-optic spectrograph FFOREST mounted at the SAO RAS 6-m telescope (BTA-6). Our self-consistent analysis of these Doppler data and TESS photometry suggests a grazing transit such that the planet obscures its host star by only a portion of the visible disc. Because of this degeneracy, the radius of TOI−1408.01 appears ill-determined with lower limit about ∼1 RJup, significantly larger than in the current TESS solution. We also derive the planet mass of 1.69 ± 0.20 MJup and the orbital period ∼4.425 d, thus making this object a typical hot Jupiter, but with a significant orbital eccentricity of 0.259 ± 0.026. Our solution may suggest that the planet is likely to experience a high tidal eccentricity migration at the stage of intense orbital rounding, or may indicate possible presence of other unseen companions in the system, yet to be detected.
Open Genes—a new comprehensive database of human genes associated with aging and longevity
Authors: Rafikova Ekaterina , Nemirovich-Danchenko Nikolay , Ogmen Anna , Parfenenkova Anna , Velikanova Anastasiia , Tikhonov Stanislav , Peshkin Leonid , Rafikov Konstantin , Spiridonova Olga , Belova Yulia , Glinin Timofey , Egorova Anastasia , Batin Mikhail
Published: September 2023

The Open Genes database was created to enhance and simplify the search for potential aging therapy targets. We collected data on 2402 genes associated with aging and developed convenient tools for searching and comparing gene features. A comprehensive description of genes has been provided, including lifespan-extending interventions, age-related changes, longevity associations, gene evolution, associations with diseases and hallmarks of aging, and functions of gene products. For each experiment, we presented the necessary structured data for evaluating the experiment's quality and interpreting the study's findings. Our goal was to stay objective and precise while connecting a particular gene to human aging. We distinguished six types of studies and 12 criteria for adding genes to our database. Genes were classified according to the confidence level of the link between the gene and aging. All the data collected in a database are provided both by an API and a user interface. The database is publicly available on a website at https://open-genes.org/.
SARS-CoV-2 Nsp8 N-terminal domain folds autonomously and binds dsRNA
Authors: Treviño Miguel Á , Pantoja-Uceda David , Laurents Douglas V , Mompeán Miguel
Published: September 2023

The SARS-CoV-2 Nsp8 protein is a critical component of the RNA replicase, as its N-terminal domain (NTD) anchors Nsp12, the RNA, and Nsp13. Whereas its C-terminal domain (CTD) structure is well resolved, there is an open debate regarding the conformation adopted by the NTD as it is predicted as disordered but found in a variety of complex-dependent conformations or missing from many other structures. Using NMR spectroscopy, we show that the SARS CoV-2 Nsp8 NTD features both well folded secondary structure and disordered segments. Our results suggest that while part of this domain corresponding to two long α-helices forms autonomously, the folding of other segments would require interaction with other replicase components. When isolated, the α-helix population progressively declines towards the C-termini but surprisingly binds dsRNA while preserving structural disorder.
Improving Prediction of Tobacco Use Over Time: Findings from Waves 1–4 of the Population Assessment of Tobacco and Health Study
Authors: Mills Sarah D , Zhang Yu , Wiesen Christopher A , Hassmiller Lich Kristen
Published: September 2023

Introduction

First-order Markov models assume future tobacco use behavior is dependent on current tobacco use and are often used to characterize patterns of tobacco use over time. Higher-order Markov models that assume future behavior is dependent on current and prior tobacco use may better estimate patterns of tobacco use.

Aims and Methods

This study compared Markov models of different orders to examine whether incorporating information about tobacco use history improves model estimation of tobacco use and estimated tobacco use transition probabilities. We used data from four waves of the Population Assessment of Tobacco and Health Study. In each Wave, a participant was categorized into one of the following tobacco use states: never smoker, former smoker, menthol cigarette smoker, non-menthol cigarette smoker, or e-cigarette/dual user. We compared first-, second-, and third-order Markov models using multinomial logistic regression and estimated transition probabilities between tobacco use states.

`Results

The third-order model was the best fit for the data. The percentage of former smokers, menthol cigarette smokers, non-menthol cigarette smokers, and e-cigarette/dual users in Wave 3 that remained in the same tobacco use state in Wave 4 ranged from 63.4% to 97.2%, 29.2% to 89.8%, 34.8% to 89.7%, and 20.5% to 80.0%, respectively, dependent on tobacco use history. Individuals who were current tobacco users, but former smokers in the prior two years, were most likely to quit.

Conclusions

Transition probabilities between tobacco use states varied widely depending on tobacco use history. Higher-order Markov models improve estimation of tobacco use over time and can inform understanding of trajectories of tobacco use behavior.

Implications

Findings from this study suggest that transition probabilities between tobacco use states vary widely depending on tobacco use history. Tobacco product users (cigarette or e-cigarette/dual users) who were in the same tobacco use state in the prior two years were least likely to quit. Individuals who were current tobacco users, but former smokers in the prior two years, were most likely to quit. Quitting smoking for at least two years is an important milestone in the process of cessation.
From adversity to advancement: leveraging war-tested approaches for the post-conflict reformation of the Ukrainian healthcare landscape
Authors: Adebusoye Favour Tope , Tan Joecelyn Kirani , Awuah Wireko Andrew , Bharadwaj Hareesha Rishab , Naeem Wara , Ferreira Tomas , Roy Sakshi , Abdul-Rahman Toufik , Lychko Volodymyr
Published: September 2023

The Russo-Ukrainian Conflict has had significant repercussions on Ukraine’s healthcare system, resulting in civilian casualties and damage to healthcare institutions. The disruption of personnel, medical supplies, and patient transportation has created considerable challenges for healthcare services. However, there are successful approaches from comparable contexts that can serve as a catalyst for post-conflict healthcare reformation in Ukraine. Key strategies include improving healthcare accessibility for marginalized populations through standardized essential health and surgical care packages, rehabilitating damaged facilities, strengthening primary care provisions, and supporting war survivors with disabilities. By adopting these proven practices, Ukraine can strengthen its healthcare system and facilitate a sustainable recovery, contributing to the country’s resilience and ensuring essential healthcare services for its population.
Purtscher-like retinopathy in systemic lupus erythematosus: clinical features, risk factors and prognosis
Authors: Meng L , Yu Q , Zhao X , Chen L , Wang Y , Zhang W , Chen H , Chen Y
Published: September 2023

Background

Purtscher-like retinopathy (PLR) is a rare ocular manifestation in systemic lupus erythematosus (SLE) with poor prognosis, but its clear risk factors and treatment consensus are still lacking.

Aim

To investigate the clinical features, risk factors and prognosis of PLR in SLE patients.

Design and methods

A retrospective analysis was conducted on SLE patients with PLR admitted at Peking Union Medical College Hospital from 2013 to 2022. Clinical data, including demographic characteristics, lupus-related features, laboratory findings and ophthalmologic examinations, were collected and analyzed. The prognosis was evaluated based on best-corrected visual acuity and ophthalmologic outcomes.

Results

Seventeen SLE patients (32 eyes) diagnosed with PLR were included, along with a random selection of 100 SLE patients without retinopathy and 100 with retinal microvasculopathy as controls. Patients with PLR had a significantly younger age, a higher proportion of hemolytic anemia, a shorter duration of SLE, a higher SLE disease activity index-2000 (SLEDAI-2K) score, higher erythrocyte sedimentation rate (ESR) values and lower hemoglobin (HGB) values than the group without retinopathy (P < 0.05). They also had a significantly higher SLEDAI-2K score, higher ESR values and higher white blood cell values (P < 0.05) than the Microvasculopathy group. The majority of eyes (22/26, 84.62%) achieved stabilization at the last follow-up, with different therapeutic strategies, while a few (4/26, 15.38%) experienced complications or progression.

Conclusion

This is the largest reported case series of PLR in SLE, which was associated with higher disease activity and poor visual prognosis. It was also associated with younger age, shorter SLE duration, concomitant hemolytic anemia, lower HGB and higher ESR value. Early recognition and prompt treatment are crucial for improving visual outcomes.
Sirtuin 1 overexpression contributes to the expansion of follicular helper T cells in systemic lupus erythematosus and may serve as an accessible therapeutic target
Authors: He Liting , Liao Wei , Wang Xin , Wang Ling , Liang Qing , Jiang Li , Yi Wanyu , Luo Shuaihantian , Liu Yu , Qiu Xiangning , Li Yaping , Liu Jun , Wu Haijing , Zhao Ming , Long Hai , Lu Qianjin
Published: September 2023

Objective

SIRT1, an NAD+-dependent deacetylase, is upregulated in CD4+ T cells from SLE patients and MRL/lpr lupus-like mice. This study aimed to explore the role of SIRT1 in follicular helper T (Tfh) cell expansion and its potential value as a therapeutic target for SLE.

Methods

Frequencies of CD4+CXCR5+PD-1+ Tfh cells in peripheral blood from SLE patients and their expression of SIRT1 and B cell lymphoma 6 (BCL-6) were determined with flow cytometry. Naïve CD4+ T cells were transfected with SIRT1-expressing lentivirus and small interfering RNA (siRNA) targeting SIRT1, respectively, and then cultured under Tfh-polarizing conditions to study the impact of SIRT1 on Tfh cell differentiation. This impact was also evaluated in both CD4+ T cells and naïve CD4+ T cells by treatment with SIRT1 inhibitors (EX527 and nicotinamide) in vitro. MRL/lpr mice and pristane-induced lupus mice were treated with continuous daily intake of nicotinamide, and their lupus phenotypes (including skin rash, arthritis, proteinuria and serum anti-dsDNA autoantibodies) were compared with those of controls.

Results

Expression of SIRT1 was elevated in Tfh cells from SLE patients and was positively correlated with Tfh cell frequencies. SIRT1 expression gradually increased during Tfh cell differentiation. Overexpression of SIRT1 by lentiviral vectors significantly promoted Tfh cell differentiation/proliferation. Reciprocally, suppressing expression of SIRT1 by siRNA and inhibiting SIRT1 activity by EX-527 or nicotinamide hindered Tfh cell expansion. Continuous daily intake of nicotinamide alleviated lupus-like phenotypes and decreased serum CXCL13 in the two mouse models.

Conclusion

SIRT1 overexpression contributed to the expansion of Tfh cells in SLE and may serve as a potential target for treatment.
TLR8 aggravates skin inflammation and fibrosis by activating skin fibroblasts in systemic sclerosis
Authors: Kong Xiangzhen , Jiang Shuai , He Qiuyu , Shi Xiangguang , Pu Weilin , Huang Yan , Ma Yanyun , Liu Qingmei , Sun Dayan , Huang Delin , Wu Fei , Li Pengcheng , Tu Wenzhen , Zhao Yinhuan , Wang Lei , Chen Yuanyuan , Wu Wenyu , Tang Yulong , Zhao Xiansheng , Zhu Qing , Gao Jian , Xu Weihong , Shui Xiaochuan , Qian Feng , Wang Jiucun
Published: September 2023

Objectives

Innate immunity significantly contributes to SSc pathogenesis. TLR8 is an important innate immune mediator that is implicated in autoimmunity and fibrosis. However, the expression, mechanism of action, and pathogenic role of TLR8 in SSc remain unclear. The aim of this study was to explore the roles and underlying mechanisms of TLR8 in SSc.

Methods

The expression of TLR8 was analysed, based on a public dataset, and then verified in skin tissues and skin fibroblasts of SSc patients. The role of TLR8 in inflammation and fibrosis was investigated using a TLR8-overexpression vector, activator (VTX-2337), inhibitor (cu-cpt-8m), and TLR8 siRNA in skin fibroblasts. The pathogenic role of TLR8 in skin inflammation and fibrosis was further validated in a bleomycin (BLM)-induced mouse skin inflammation and fibrosis model.

Results

TLR8 levels were significantly elevated in SSc skin tissues and myofibroblasts, along with significant activation of the TLR8 pathway. In vitro studies showed that overexpression or activation of TLR8 by a recombinant plasmid or VTX-2337 upregulated IL-6, IL-1β, COL I, COL III and α-SMA in skin fibroblasts. Consistently, both TLR8-siRNA and cu-cpt-8m reversed the phenotypes observed in TLR8-activating fibroblasts. Mechanistically, TLR8 induces skin fibrosis and inflammation in a manner dependent on the MAPK, NF-κB and SMAD2/3 pathways. Subcutaneous injection of cu-cpt-8m significantly alleviated BLM-induced skin inflammation and fibrosis in vivo.

Conclusion

TLR8 might be a promising therapeutic target for improving the treatment strategy for skin inflammation and fibrosis in SSc.
Giving weight to incretin-based pharmacotherapy for obesity-related sleep apnea: a revolution or a pipe dream?
Authors: Grunstein Ronald R , Wadden Thomas A , Chapman Julia L , Malhotra Atul , Phillips Craig L
Published: September 2023

Obesity is a chronic disease affecting over 670 million adults globally, with multiple complications including obstructive sleep apnea (OSA). Substantial weight loss in patients with obesity-related OSA can reduce or even eliminate OSA as well as reduce sleepiness and improve cardio-metabolic health. Evidence suggests that these improvements exceed those that occur with device-based OSA therapies like continuous positive airway pressure which continue to be the first-line of therapy. Resistance to weight management as a first-line strategy to combat OSA could arise from the complexities in delivering and maintaining adequate weight management, particularly in sleep clinic settings. Recently, incretin-based pharmacotherapies including glucagon-like peptide 1 (GLP-1) receptor agonists alone or combined with glucose-dependent insulinotropic polypeptide (GIP) receptor agonists have been developed to target glycemic control in type 2 diabetes. These medications also slow gastric emptying and reduce energy intake. In randomized, placebo-controlled trials of these medications in diabetic and non-diabetic populations with obesity, participants on active medication lost up to 20% of their body weight, with corresponding improvements in blood pressure, lipid levels, physical functioning, and fat mass loss. Their adverse effects are predominantly gastrointestinal-related, mild, and transient. There are trials currently underway within individuals with obesity-related OSA, with a focus on reduction in weight, OSA severity, and cardio-metabolic outcomes. These medications have the potential to substantially disrupt the management of OSA. Pending coming data, we will need to consider pharmacological weight loss as a first-line therapy and how that influences training and management guidelines.
Identifying emergent themes of students’ transition to university mathematics: a qualitative inquiry with a focus on affective factors
Authors: Uysal Seyda , Clark Kathleen Michelle
Published: September 2023

We present the findings from our inquiry conducted between spring 2019 and spring 2020. It focused on women and students from underrepresented or marginalized populations as they navigated moments in their transition from school to university mathematics, or the secondary-tertiary transition (STT) in mathematics. We draw on Di Martino & Zan’s (2010) three-dimensional model of attitude (TMA), in which they reify the role of various affective factors of the STT. We used this model to capture the three affective dimensions of the STT: students’ vision of mathematics, their perceived competence in mathematics and their emotional disposition toward mathematics. Our qualitative data included participant interviews, surveys, seminar reflection diaries, seminar recordings and other student artifacts gathered from seminar sessions. In our research, we found differences and commonalities with regard to these three dimensions of the TMA between students who pursued a pure mathematics (PM) degree and those who pursued a combined degree in PM and secondary mathematics teaching (SMT) in the USA. We discuss future directions that can aid women and other historically marginalized students in navigating during STT.
Low-dose inhalation exposure to trichloroethylene induces dopaminergic neurodegeneration in rodents
Authors: Adamson Ashley , Ilieva Neda , Stone William J , De Miranda Briana R
Published: September 2023

Trichloroethylene (TCE) is one of the most pervasive environmental contaminants in the world and is associated with Parkinson disease (PD) risk. Experimental models in rodents show that TCE is selectively toxic to dopaminergic neurons at high doses of ingestion, however, TCE is a highly volatile toxicant, and the primary pathway of human exposure is inhalation. As TCE is a highly lipophilic, volatile organic compound (VOC), inhalation exposure results in rapid diffusion throughout the brain, avoiding first-pass hepatic metabolism that necessitated high doses to recapitulate exposure conditions observed in human populations. We hypothesized that inhalation of TCE would induce significantly more potent neurodegeneration than ingestion and better recapitulate environmental conditions of vapor intrusion or off gassing from liquid TCE. To this end, we developed a novel, whole-body passive exposure inhalation chamber in which we exposed 10-month-old male and female Lewis rats to 50 ppm TCE (time weighted average, TWA) or filtered room air (control) over 8 weeks. In addition, we exposed 12-month-old male and female C57Bl/6 mice to 100 ppm TCE (TWA) or control over 12 weeks. Both rats and mice exposed to chronic TCE inhalation showed significant degeneration of nigrostriatal dopaminergic neurons as well as motor and gait impairments. TCE exposure also induced accumulation of pSer129-αSyn in dopaminergic neurons as well as microglial activation within the substantia nigra of rats. Collectively, these data indicate that TCE inhalation causes highly potent dopaminergic neurodegeneration and recapitulates some of the observed neuropathology associated with PD, providing a future platform for insight into the mechanisms and environmental conditions that influence PD risk from TCE exposure.
Monitoring Corynespora cassiicola Resistance to Boscalid, Trifloxystrobin, and Carbendazim in China
Authors: Zhou Rongjia , Sun Bingxue , Zhu Guangxue , Xie Xuewen , Chai Ali , Li Lei , Fan Tengfei , Li Baoju , Shi Yanxia
Published: September 2023

Cucumber leaf spot (CLS), caused by Corynespora cassiicola, is a serious disease of greenhouse cucumbers. With frequent use of existing fungicides, C. cassiicola has developed resistance to some of them, with serious implications for the control of CLS in the field. With a lack of new fungicides, it is necessary to use existing fungicides for effective control. Therefore, this study monitored the resistance of C. cassiicola to three commonly used and effective fungicides, boscalid, trifloxystrobin, and carbendazim, from 2017 to 2021. The frequency of resistance to boscalid showed an increasing trend, and the highest frequency was 85.85% in 2020. The frequency of resistance to trifloxystrobin was greater than 85%, and resistance to carbendazim was maintained at 100%. Among these fungicides, strains with multiple resistance to boscalid, trifloxystrobin, and carbendazim were found, accounting for 32.00, 25.25, 33.33, 43.06, and 37.24%, respectively. Of the strains that were resistant to boscalid, 87% had CcSdh mutations, including seven genotypes: B-H278L/Y, B-I280V, C-N75S, C-S73P, D-D95E, and D-G109V. Also, six mutation patterns of the Ccβ -tubulin gene were detected: E198A, F167Y, E198A&M163I, E198A&F167Y, M163I&F167Y, and E198A&F200C. Detection of mutations of the CcCytb gene in resistant strains showed that 98.8% were found to have only the G143A mutation. A total of 27 mutation combinations were found and divided into 14 groups for analysis. The resistance levels differed according to genotype. The development of genotypes showed a complex trend, increasing from 4 in 2017 to 13 in 2021 and varying by region. Multiple fungicide resistance is gradually increasing. Therefore, it is necessary to understand the types of mutations and the trend of resistance to guide the use of fungicides to achieve disease control.
A Novel All-Inside Knotless Arthroscopic Deltoid Ligament Repair
Authors: Tansey Patrick J. , Castillo Isaac , Panchbhavi Vinod K.
Published: September 2023

Injury to the deltoid ligamentous complex is frequently observed in ankle fractures and multidirectional instability. While open deltoid repair has traditionally been performed, arthroscopic repair techniques have also been described. We present a new method to perform a knotless medial ligament complex repair utilizing an all-inside technique and provide short-term outcomes of our clinical series.

Level of Evidence: Level V, expert opinion.
Factors related to medication adherence in patients with hypertension in Iran: a systematic review study
Authors: Maleki Golara , Norian Rohollah , Moeini Babak , Barati Majid , Maleki Shahnaz , Afshari Maryam
Published: September 2023

Objectives

This study aimed to review the available studies of the factors in Iranian hypertensive patients’ adherence to drug treatment.

Methods

Four Persian databases and seven English databases were searched. The articles, which were published from 2000 to 2022 in Persian and English and examined the adherence to drug treatment in the Iranian population of adults with high blood pressure, were reviewed. Based on the primary examination, 31 of the initial 1062 articles met the inclusion criteria and were included in the analysis. The evidence, which was provided by the examined articles, was summarized and discussed using the 5-dimensional framework of adherence to long-term treatments, which was developed by WHO.

Results

The factors that significantly correlated with adherence to drug treatment in the examined studies were: (1) factors that were related to the health team or the health system: patients’ satisfaction with their doctor-patient relationship; (2) factors that were related to the conditions: the number of concomitant diseases, high quality of life and the implementation of effective interventions; (3) factors which were related to the treatment: long duration of illness, short intervals between the visits, duration of treatment, lower numbers of drugs, and the patient’s blood pressure control; and (4) factors that were related to the patient: self-efficacy, health literacy, social support, locus of control, illness perception, beliefs, attitude, knowledge, and cues to action.

Conclusion:

It is possible to draw definite conclusions about the factors which affect adherence to drug treatment in patients with high blood pressure because most of the relevant studies have been cross-sectional. Therefore, in the future, valuable results can be obtained by conducting more studies that preferably use objective instruments for assessing adherence to drug treatment
Central blood pressure obtained by cuff-based oscillometry as a determinant of left ventricular hypertrophy in hypertensive patients
Authors: Abdelmegid Mohamed Aboel-Kassem F. , Fouad Doaa A. , Beshay Nardeen W.M. , Mahran Dalia G. , Shams-eddin Hamdy
Published: September 2023

Objective

Limited and conflicting data have been reported on the prognostic relevance of central blood pressure (CBP) compared with brachial blood pressure (BP) in the anticipation of hypertension-mediated organ damage and the majority of data derived using applanation tonometry with its known complexities. The objective of the present study was to investigate the diagnostic factors of left ventricular hypertrophy (LVH) with a special highlight on the utility of non-invasive oscillometric CBP measurement and derived hemodynamic indices compared to brachial BP as indicators of LVH.

Methods

This cross-sectional study included 300 hypertensive patients (mean age 55.3 years, 61.3% female, 51.7% obese) with a mean duration of hypertension was 5.8 years. They underwent measurement of brachial BP, using a mercury sphygmomanometer, and CBP, using a Mobil-O-Graph, alongside the determination of left ventricular (LV) mass by two-dimensional transthoracic echocardiography. LVH and LV geometric patterns were defined by LV mass index/height2.7 and relative wall thickness.

Results

Bivariate then multivariate analysis showed that age, BMI, central systolic BP (SBP), and pulse wave velocity (PWV) were significant determinants of LVH and optimally controlled brachial BP was a significant negative determinant for LVH. Central SBP had an acceptable diagnostic performance to determine LVH in patients with hypertension (AUC = 0.722, 95% confidence interval: 0.618–0.824, SE = 0.21, P-value <0.001). Using one-way ANOVA, a comparison of means among age groups showed that the steady increase in central SBP and PWV with aging was greater among LVH patients than non-LVH patients.

Conclusion

Estimated central SBP using Mobil-O-Graph showed a significantly higher correlation to LVH than brachial SBP values. The consistent increase in central SBP and PWV with aging was greater among LVH patients than non-LVH patients.
Impact of home blood pressure monitors on self-monitoring and control of blood pressure in vulnerable adults
Authors: Shi Yufei , McAdam-Marx Carrie , Downes Jessica M.
Published: September 2023

To evaluate associations between home blood pressure monitoring (HBPM) and blood pressure (BP) in vulnerable adults during the COVID-19 pandemic, when access to in-person care was restricted. A retrospective cohort study was conducted in adults with hypertension or elevated BP given a home BP monitor vs. usual care. Change in BP from baseline to follow-up was compared between groups, controlling for potential confounders. Subgroup analyses of BP outcomes were also assessed in patients age >50 years. There was no difference in SBP reduction between n = 82 HBPM patients (−11.7/−2.9 mmHg) and n = 280 usual care patients (−12.5/−5.8 mmHg; P> 0.05). Results were similar in multivariable analysis controlling for potential confounders [coefficient 0.44, 95% confidence interval (CI) −3.98 to 4.87]. However, in the subgroup of patients aged>50 years, there was a significant association between SBP reduction and HBPM in the multivariable analyses (coefficient −7.2, 95% CI −13.8 to −0.62, P= 0.032). HBPM use was not associated with BP reduction in vulnerable adults overall during high telehealth use. An association between SBP reduction and HBPM was observed in those aged>50 years. Targeting limited HBPM resources to those aged >50 years old may have the most impact on BP.
Screening for orthostatic hypotension in the geriatric population in a real-world primary care setting reduces prescribed antihypertensive medications
Authors: Kaye Matthew G. , Rutowski James , Aftab Hamza , Pandey Rohan , Khan Raheel , Kalot Mohamad A. , Anand Renata , Graham Susan P.
Published: September 2023

Background

To determine if outpatient screening for orthostatic hypotension (OH) in the geriatric population results in fewer prescribed antihypertensive medications and if a relationship exists between OH and specific pharmacologic classes of antihypertensive medications.

Materials and methods

Patients ≥ 65 years were screened for OH, defined as a decrease in systolic blood pressure (SBP) ≥ 20 mm Hg or a decrease in diastolic blood pressure (DBP) ≥ 10 mm Hg after standing for 3 minutes. Sitting blood pressure (BP) was measured after patients had been seated quietly in an exam room. Patients then stood for approximately 3 minutes at which time standing BP was recorded.

Results

OH prevalence was 18%. Standing DBP was significantly different between the two groups (70 mmHg ± 18, 80 mmHg ± 13, P = 0.007). Compared to patients without OH, patients with OH were more likely to have been previously prescribed beta-blockers (56% vs. 32%, P = 0.056) and potassium-sparing diuretics (11% vs. 1%, P = 0.026). Physicians discontinued an antihypertensive medication more often in patients who screened positive for OH than in to those who did not (17% vs. 4%, P = 0.037). Calcium channel blockers were the most frequently discontinued class of medication.

Conclusion

Asymptomatic OH is prevalent in geriatric patients. Screening for OH may lead to de-escalation of antihypertensive regimen and a reduction in polypharmacy. Positive screening for OH was associated with de-prescribing of antihypertensive medications. Prior use of beta-blockers and potassium-sparing diuretics was most largely associated with OH.
Bidirectional association between non-alcoholic fatty liver disease and fatty pancreas: a systematic review and meta-analysis
Authors: Wongtrakul Wasit , Untaaveesup Suvijak , Pausawadi Nonthalee , Charatcharoenwitthaya Phunchai
Published: September 2023

Background

Accumulating evidence suggests a potential relationship between non-alcoholic fatty liver disease (NAFLD) and fatty pancreas, as both conditions are associated with fat deposition in the liver and pancreas, respectively. The meta-analysis aimed to investigate the bidirectional association between NAFLD and fatty pancreas, as well as their respective effects on disease severity.

Methods

A systematic search of the EMBASE and MEDLINE databases, from inception to August 2022, was conducted to identify observational studies examining the association between NAFLD and fatty pancreas, as well as their impact on disease severity. The pooled odds ratio (OR) with a 95% confidence interval (CI) was estimated using a random-effects model.

Results

Our analysis included 26 case-control or cross-sectional studies, comprising 67,803 participants. We observed a significant association between NAFLD and an increased odds of having fatty pancreas (OR, 6.18; 95% CI, 4.49–8.51; I2
 = 92%). Similarly, fatty pancreas was significantly associated with an increased odds of having NAFLD (OR, 9.56; 95% CI, 5.09–17.95; I2
 = 83%). Furthermore, the presence of fatty pancreas was associated with a 1.75-fold increased risk of severe NAFLD based on ultrasonographic classification (95% CI, 1.46–2.10; I2
 = 0%). Among NAFLD patients, the coexistence of fatty pancreas was associated with a trend towards increased odds of having non-alcoholic steatohepatitis (OR, 3.52; 95% CI, 0.65–18.93; I2
 = 82%) and advanced fibrosis (OR, 2.47; 95% CI, 0.52–11.80; I2
 = 76%).

Conclusion

This meta-analysis discloses a bidirectional association between NAFLD and fatty pancreas, emphasizing the importance of understanding the intricate relationship between these two conditions.
Evaluation of treatment response by Hopkins criteria on18F FDG PET-CT in patients of non-small cell lung cancer and its comparison with PERCIST response criteria
Authors: Dang Shreya , Shivdasani Divya , Pereira Melvika , Singh Natasha , Rungta Rachita , Roy Debdip , Kesariya Jugal
Published: September 2023

Aim

To assess treatment response on FDG PET-CT in NSCLC patients by visual Hopkins score compared to PERCIST criteria and its potential for prognostication (or its correlation with survival).

Methods

Forty-four NSCLC patients with baseline and post-treatment FDG PET-CT scans were included, and interpreted using Hopkins and PERCIST criteria classifying patients into responders and non-responders. PERCIST-based CMR and PMR, and Hopkins Scores 1,2,3 were classified responders. PERCIST-based SD and PD and Hopkins scores 4,5 were classified as non-responders. Patients were followed upto 24 months after treatment completion. Cohen kappa for inter-criteria agreement and Kaplan Meir curve for overall survival (OS) analysis done.

Results

Out of 44 patients, PERCIST classified 27 (61.3%) as responders and 17 (38.6%) as non-responders, whereas Hopkins classified 12 patients (27.3%) as responders and 32 (72.7%) as non-responders. Inter-criteria agreement was low (kappa=0.19) with discordance in 45.5% of patients. Eighteen of 20 discordant cases were non-responders on Hopkins and responders on PERCIST, of which 88.8% were non-responders on follow-up as predicted by Hopkins. PERCIST responders had OS of 96.4% and 64.3% at 9 and 24 months, respectively, while non-responders OS was 93.5% and 40.2% at 9 and 24 months, respectively (P-value = 0.049). However, responders on Hopkins had OS of 100% at 24 months, whereas non-responders had OS of 93.5% and 51.5% at 9 and 24 months, respectively (P-value = 0.232).

Conclusion

Semi-quantitative PERCIST and visual Hopkins criteria show low inter-criteria agreement, with visual criteria better-predicting survival in patients of NSCLC.
Hospitalists in Pediatric Oncology/Stem Cell Transplant: Successes and Opportunities
Authors: Ghuman Amita , Devine Kaitlin J. , Milligan Michelle P. , Reilly Anne , Freedman Jason L.
Published: September 2023

As hospitalized pediatric patients have grown in number and complexity, and residency structural changes have reduced resident coverage, inpatient care models have changed to include additional providers at the “front line.” Hospitalists are increasingly employed in general pediatric units, but in specialized inpatient areas, hospitalist care models are less common. Hospitalist programs in pediatric oncology are few and unique, and thus there are limited data assessing this role. Here we describe the oncology/stem cell transplant hospitalist program at the Children’s Hospital of Philadelphia with a survey project to assess the perceptions of physicians in the role. Hospitalists from 2017 to 2019 (n=26) were surveyed to assess nonclinical roles and job satisfaction. With a response rate of 84.6%, all respondents concurred work-life balance, hours, and flexibility are attractive and found the field intellectually stimulating. Most (86.4%) agreed there were significant academic opportunities. The vast majority felt this job was valuable in attaining career and personal goals; 95.5% were happy they accepted this position. As the pediatric oncology/stem cell transplant hospitalist position is a viable, versatile career path providing ample academic opportunities and job satisfaction, the expansion of such a model within our institution and others should be well received.
Frontline Hyper-CVAD Plus Venetoclax for Pediatric Blastic Plasmacytoid Dendritic Cell Neoplasm
Authors: He Jiasen , Garcia Miriam B. , Connors Jeremy S. , Nuñez Cesar A. , Quesada Andres E. , Gibson Amber , Roth Michael , Cuglievan Branko , Pemmaraju Naveen , McCall David
Published: September 2023

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy, especially in pediatrics, that can involve the bone marrow, skin, lymph nodes, and central nervous system (CNS). Given its variable clinical presentation, coupled with an immunohistochemistry pattern (CD4, CD56, TCF4, TCL-1, and CD123 positivity) that differs from other myeloid neoplasms, the diagnosis of BPDCN can be missed. Limited data are available to guide the treatment of pediatric BPDCN. Herein, we report a case of a pediatric patient who had BPDCN with central nervous system, orbital, and skin involvement. This patient achieved complete remission after receiving modified hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone with venetoclax and intrathecal chemotherapy. He remains disease-free 200 days after receiving a stem cell transplant. This represents the first known published pediatric case using a modified hyper-CVAD plus venetoclax regimen for treating a pediatric BPDCN patient in the frontline setting.
Genomic Analysis in the Categorization of Poorly Differentiated Primary Liver Carcinomas
Authors: Kikuchi Alexander T. , Umetsu Sarah , Joseph Nancy , Kakar Sanjay
Published: September 2023

A subset of primary liver carcinomas (PLCs) cannot be classified as hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (iCCA) based on morphology and immunohistochemistry (IHC). This includes tumors with morphology suggestive of HCC but lacking hepatocellular marker expression, tumors with ambiguous morphology characterized by co-expression of hepatocellular and cholangiocytic markers, and undifferentiated pleomorphic carcinomas with no discernible line of differentiation on morphology or IHC. This study examines the role of genomic analysis in the categorization of these tumors. Genomic analysis was performed on 16 PLCs that could not be definitely classified as HCC or iCCA based on morphology and IHC using a capture-based next-generation sequencing assay (n=15) or single gene mutational analysis (n=1). Genomic alterations in TERT promoter were seen in 9/16 cases (56%) and strongly favored HCC. Genomic alterations favoring iCCA were seen in 5/16 cases (31%) and included mutations in IDH1, PBRM1, BAP1, and ERBB2, as well as FGFR2 fusion. Genomic changes were helpful in classifying 14/16 (87%) PLCs. Though not specific, these genomic alterations can provide valuable diagnostic clues in selected morphologically and immunohistochemically unclassifiable cases. Given the important differences in management between HCC and iCCA, routine use of genomic analysis in diagnostically challenging settings should be considered.
Brown adipose tissue: can it keep us slim? A discussion of the evidence for and against the existence of diet-induced thermogenesis in mice and men
Authors: Nedergaard Jan , von Essen Gabriella , Cannon Barbara
Published: September 2023

The issue under discussion here is whether a decrease in the degree of UCP1 activity (and brown adipose tissue activity in general) could be a cause of obesity in humans. This possibility principally requires the existence of the phenomenon of diet-induced thermogenesis. Obesity could be a consequence of a reduced functionality of diet-induced thermogenesis. Experiments in mice indicate that diet-induced thermogenesis exists and is dependent on the presence of UCP1 and thus of brown adipose tissue activity. Accordingly, many (but not all) experiments indicate that in the absence of UCP1, mice become obese. Whether similar mechanisms exist in humans is still unknown. A series of studies have indicated a correlation between obesity and low brown adipose tissue activity, but it may be so that the obesity itself may influence the estimates of brown adipose tissue activity (generally glucose uptake), partly explaining the relationship. Estimates of brown adipose tissue catabolizing activity would seem to indicate that it may possess a capacity sufficient to help maintain body weight, and obesity would thus be aggravated in its absence.

This article is part of a discussion meeting issue ‘Causes of obesity: theories, conjectures and evidence (Part II)’.
Questioning the foundations of the gut microbiota and obesity
Authors: Dalby Matthew J.
Published: September 2023

The role of the gut microbiota in determining body fatness has been a prominent area of research and has received significant public attention. Based largely on animal studies, recent attempts to translate these findings into interventions in humans have not been successful. This review will outline the key mouse research that initiated this area of study, examine whether those results warranted the initial enthusiasm and progress into human studies, and examine whether later follow-up research supported earlier conclusions. It will look at whether the absence of a gut microbiota protects germ-free mice from obesity, whether microbiota can transfer obesity into germ-free mice, the evidence for the role of immune system activation as a causal mechanism linking the gut microbiota to body weight, and consider the evidence for effects of individual bacterial species. Finally, it will examine the outcomes of randomized controlled trials of microbiota transfer in human participants that have not shown effects on body weight. With a more critical reading, early studies did not show as large an effect as first appeared and later research, including human trials, has failed to support a role of the gut microbiota in shaping body weight.

This article is part of a discussion meeting issue ‘Causes of obesity: theories, conjectures and evidence (Part II)’.
Obesity and psychological distress
Authors: Steptoe Andrew , Frank Philipp
Published: September 2023

The relationship between high body weight and mental health has been studied for several decades. Improvements in the quality of epidemiological, mechanistic and psychological research have brought greater consistency to our understanding of the links. Large-scale population-based epidemiological research has established that high body weight is associated with poorer mental health, particularly depression and subclinical depressive symptoms. There is some evidence for bidirectional relationships, but the most convincing findings are that greater body weight leads to psychological distress rather than the reverse. Particular symptoms of depression and distress may be specifically related to greater body weight. The psychological stress induced by weight stigma and discrimination contributes to psychological distress, and may in turn handicap efforts at weight control. Heightened systemic inflammation and dysregulation of the hypothalamic-pituitary-adrenal axis are biological mechanisms that mediate in part the relationship of greater body weight with poorer mental health. Changing negative societal attitudes to high body weights would improve the wellbeing of people living with obesity, and promote more effective weight-inclusive attitudes and behaviours in society at large, particularly in healthcare settings.

This article is part of a discussion meeting issue ‘Causes of obesity: theories, conjectures and evidence (Part II)’.
Causal models and causal modelling in obesity: foundations, methods and evidence
Authors: Zoh Roger S. , Yu Xiaoxin , Dawid Philip , Smith George Davey , French Stephen J. , Allison David B.
Published: September 2023

Discussing causes in science
, if we are to do so in a way that is sensible, begins at the root. All too often, we jump to discussing specific postulated causes but do not first consider what we mean by, for example,
causes
of obesity or how we discern whether something is a cause. In this paper, we address what we mean by a cause, discuss what might and might not constitute a reasonable causal model in the abstract, speculate about what the causal structure of obesity might be like overall and the types of things we should be looking for, and finally, delve into methods for evaluating postulated causes and estimating causal effects. We offer the view that different meanings of the concept of causal factors in obesity research are regularly being conflated, leading to confusion, unclear thinking and sometimes nonsense. We emphasize the idea of different kinds of studies for evaluating various aspects of causal effects and discuss experimental methods, assumptions and evaluations. We use analogies from other areas of research to express the plausibility that only inelegant solutions will be truly informative. Finally, we offer comments on some specific postulated causal factors.

This article is part of a discussion meeting issue ‘Causes of obesity: theories, conjectures and evidence (Part II)’.
Food insecurity as a cause of adiposity: evolutionary and mechanistic hypotheses
Authors: Bateson Melissa , Pepper Gillian V.
Published: September 2023

Food insecurity (FI) is associated with obesity among women in high-income countries. This seemingly paradoxical association can be explained by the insurance hypothesis, which states that humans possess evolved mechanisms that increase fat storage to buffer against energy shortfall when access to food is unpredictable. The evolutionary logic underlying the insurance hypothesis is well established and experiments on animals confirm that exposure to unpredictable food causes weight gain, but the mechanisms involved are less clear. Drawing on data from humans and other vertebrates, we review a suite of behavioural and physiological mechanisms that could increase fat storage under FI. FI causes short-term hyperphagia, but evidence that it is associated with increased total energy intake is lacking. Experiments on animals suggest that unpredictable food causes increases in retained metabolizable energy and reductions in energy expenditure sufficient to fuel weight gain in the absence of increased food intake. Reducing energy expenditure by diverting energy from somatic maintenance into fat stores should improve short-term survival under FI, but the trade-offs potentially include increased disease risk and accelerated ageing. We conclude that exposure to FI plausibly causes increased adiposity, poor health and shorter lifespan.

This article is part of a discussion meeting issue ‘Causes of obesity: theories, conjectures and evidence (Part II)’.
Statistical Analysis Plan for the Primary and Selected Secondary Endpoints in the ENHANCED-SPS Study
Authors: Balzer Laura B. , Kabami Jane ,   the ENHANCED-SPS Study Team
Published: September 2023

This document provides the statistical analytic plan (SAP) for the ENHANCED-SPS study, a cluster randomized trial to evaluate the effects of peer-led, multicomponent intervention on viral suppression and other care outcomes among pregnant and breastfeeding women with HIV in South Western Uganda (Clinicaltrials.gov:NCT04122144). The SAP was locked prior to unblinding and effect estimation. This SAP was embargoed until August 31, 2023 when it was submitted to medRxiv.