bluuebunny/crossref_metadata_2025 huggingface dataset:
Lipoprotein(a) and functional outcome of acute ischemic stroke when discordant with low-density lipoprotein cholesterol
Authors: Dong Wenjing , Zhong Xiaoyan , Yuan Ke , Miao Mengyuan , Zhai Yujia , Che Bizhong , Xu Tan , Xu Xiang , Zhong Chongke
Published: August 2023

Background

Several studies have indicated that residual cardiovascular risk might be associated with elevated lipoprotein(a) [Lp(a)] even in the setting of controlled low-density lipoprotein cholesterol (LDL-C). We aimed to prospectively examine the association between Lp(a) and unfavorable functional outcome among patients with acute ischemic stroke when Lp(a) and LDL-C were discordant.

Methods

Based on samples from the Infectious Factors, Inflammatory Markers and Prognosis of Acute Ischemic Stroke study, 973 patients with baseline plasma Lp(a) levels were included. The primary outcome was the composite outcome of death or major disability (modified Rankin Scale score of 3–6) at 6 months. Logistic regression models were used to estimate the risk for the primary outcome. Discordance analyses were performed, using difference in percentile units (>10 units), to detect the relative risk when Lp(a) and LDL-C were discordant.

Results

In total, 201 (20.7%) participants experienced major disability or death at 6 months. The multivariable-adjusted odds ratio (OR) for the highest quartile was 1.88 [95% confidence interval (CI): 1.16–3.04] compared with the lowest quartile. Each 1-SD higher log-Lp(a) was associated with a 23% increased risk (95% CI: 2%–47%) for the primary outcome. Compared with the concordant group, the high Lp(a)/low LDL-C discordant group was associated with increased risk for the primary outcome (adjusted OR: 1.59, 95% CI: 1.01–2.52).

Conclusions

Elevated plasma Lp(a) levels were associated with increased risk of major disability and death at 6 months. Discordantly high Lp(a)/low LDL-C was associated with an unfavorable functional outcome, supporting the predictive potential of plasma Lp(a) after ischemic stroke, especially when discordant with LDL-C.

Key messages What is already known on this topic Previous studies have indicated that a positive association between increased lipoprotein(a) [Lp(a)] and cardiovascular disease risk remained even in patients who achieved controlled low-density lipoprotein cholesterol (LDL-C) levels. The findings of studies exploring the association between Lp(a) and unfavorable clinical outcomes of stroke were inconsistent, and whether Lp(a) can predict the risk of unfavorable functional outcome in stroke patients when Lp(a) and LDL-C levels are discordant remains unknown. What this study adds Elevated plasma Lp(a) levels were associated with increased risk of major disability and death at 6 months beyond LDL-C levels in acute ischemic stroke patients. How this study might affect research, practice, or policy The combination of LDL-C-lowering therapies and Lp(a)-lowering therapies may have better clinical efficacy for patients with ischemic stroke, and it is of great clinical interest to further explore this possibility in dedicated randomized trials.
When Spirit Calls: A Phenomenological Approach to Healthy Voice-Hearers
Authors: Luhrmann Tanya Marie , Chen Xialing Ann , Baumeister David , Peters Emmanuelle
Published: August 2023

We present a mixed-methods study, from an anthropological perspective, of 22 healthy voice-hearers ie, people who report hearing voices but have no need for clinical care. They were interviewed using the Varieties Of Individual Voice-Experiences Scale (VOICES), a new scale assessing phenomenology, beliefs and relationships with voices, and their emotional and behavioral impact. Despite in many cases hearing voices daily, they report remarkably little distress, with almost all mentioning a positive impact on their life. Most interpreted their voices as spirits, and spoke of learning to understand, to manage, and even to train their experience of communicating with spirits productively. There was, however, considerable diversity in their voice experiences. Some described experiences they seemed to have discovered after starting a practice. Others described reaching for a practice to make sense of unusual experiences. This raises the possibility that cultural ideas about spirit communication may have two effects. On the one hand, they may help those who begin to hear voices involuntarily to interpret and manage their experience in a non-threatening way, through a meaning framework imposed on experiences. On the other hand, it also suggests that cultural ideas about spirit communication may lead some people to identify some thoughts as voices, and to come to feel that those thoughts are generated outside of themselves, through a meaning-framework shaping experiences. This should remind us that the culture-mind relationship is complex. There may be different kinds of phenomena described by individuals as “voices,” with practice and interpretation changing how these phenomena are experienced.
A comprehensive characterization of longevity and culling reasons in Canadian Holstein cattle based on various systematic factors
Authors: de Souza Taiana Cortez , Pinto Luis Fernando Batista , da Cruz Valdecy Aparecida Rocha , de Oliveira Hinayah Rojas , Pedrosa Victor Breno , Oliveira Gerson A , Miglior Filippo , Schenkel Flávio S , Brito Luiz F
Published: August 2023

The decision of premature culling cows directly impacts the profitability of dairy farms. A comprehensive characterization of the primary causes of culling reasons would greatly improve both management and selection objectives in dairy cattle breeding programs. Therefore, this study aimed to analyze the temporal frequencies of 34 culling reasons in Canadian Holstein cows. After data editing and quality control, records from 3,096,872 cows culled from 9,683 herds spread across Canada were used for the analyses covering the periods from 1996 to 2020. Reproductive issues were the main culling reason accounting for 23.02%, followed by milk production (20.82%), health (20.39%), conformation problems (13.69%), economic factors (13.10%), accidents (5.67%), age-related causes (1.67%), and workability (1.63%). Nearly fifty-eight percent of cows were culled after 47 months of age. The observed frequencies of culling due to economic factors were lower than expected from 1996 to 2014 and higher than expected between 2015 and 2020. Reproduction issues had the highest culling frequencies during fall (24.54%), winter (24.02%), and spring (22.51%), while health issues were the most frequent (22.51%) culling reason in the summer season. Health issues (25.50%) and milk production (27.71%) were the most frequent culling reasons in the provinces of Quebec and Ontario, respectively. Reproductive issues showed the highest frequency across climates based on the Köppen climate classification, except for Csb (Dry-summer subtropical or Mediterranean climate) and Bsk (Middle latitude steppe climate), which correspond to small regions in Canada, where production was the most frequent culling reason (29.42% and 21.56%, respectively). Reproductive and milk performance issues were the two main culling reasons in most ecozones, except in Boreal Shield and Atlantic Marine, where health issues had the highest frequencies (25.12 and 23.75%, respectively). These results will contribute to improving management practices and selective decisions to reduce involuntary culling of Holstein cows.
Ovarian antral follicles metabolize imidacloprid in vitro
Authors: Mourikes Vasiliki E , Santacruz-Márquez Ramsés , Deviney Ashley , Laws Mary J , Ulanov Alexander V , La Frano Michael R , Flaws Jodi A
Published: August 2023

Neonicotinoid insecticides are synthetic nicotine derivatives that have high affinity for invertebrate nicotine receptors and low affinity for mammalian nicotine receptors. However, imidacloprid (IMI), the most commonly used neonicotinoid, can be bioactivated by the liver in mammals to desnitro-imidacloprid, an intermediate metabolite that effectively binds and activates mammalian receptors. However, it is not known if other tissues such as the ovaries can metabolize IMI. Thus, the present study tested the hypothesis that ovarian antral follicles metabolize and bioactivate IMI. Antral follicles were dissected from the ovaries of CD-1 mice and cultured in media containing dimethyl sulfoxide or IMI (0.2–200 µg/ml) for 48 and 96 h. Media were subjected to liquid chromatography-mass spectrometry for detection of phase I IMI metabolites. Follicles from the cultures were used for gene expression analysis of metabolic enzymes associated with IMI metabolism. All IMI metabolites were detected at 48 and 96 h. Oxidized IMI intermediates were detected in media from cultured follicles, but not environmental controls. Reduced IMI intermediates were detected in media from cultured follicles and the environmental controls. At 48 h, IMI did not affect expression of any metabolic enzymes compared with control. At 96 h, IMI induced Cyp2e1 and Cyp4f18 compared with control. These data indicate that mouse ovarian follicles metabolize IMI and that IMI induces ovarian Cyp expression over time.
Muscle p62 stimulates the expression of antioxidant proteins alleviating cancer cachexia
Authors: Yamada Mami , Warabi Eiji , Oishi Hisashi , Lira Vitor A. , Okutsu Mitsuharu
Published: August 2023

Oxidative stress plays an important role in skeletal muscle atrophy during cancer cachexia, and more glycolytic muscles are preferentially affected. Sequestosome1/SQSTM1 (i.e., p62), particularly when phosphorylated at Ser 349 (Ser 351 in mice), competitively binds to the Kelch‐like ECH‐associated protein 1 (Keap1) activating Nuclear factor erythroid 2‐related factor 2 (Nrf2). Nrf2 then stimulates the transcription of antioxidant/electrophile‐responsive elements in target genes. However, a potential role for p62 in the protection of muscle wasting in cachexia remains to be determined. Here, using the well‐established cachexia‐inducing model of Lewis Lung Carcinoma (LLC) in mice we demonstrate higher expression of antioxidant proteins (i.e., NQO1, HO‐1, GSTM1, CuZnSOD, MnSOD, and EcSOD) in the more oxidative and cachexia resistant soleus muscle than in the more glycolytic and cachexia prone extensor digitorum longus muscle. This was accompanied by higher p62 (total and phosphorylated) and nuclear Nrf2 levels in the soleus, which were paralleled by higher expression of proteins known to either phosphorylate or promote p62 phosphorylation (i.e., NBR1, CK1, PKCδ, and TAK1). Muscle‐specific p62 gain‐of‐function (i.e., in p62 mTg mice) activated Nrf2 nuclear translocation and increased the expression of multiple antioxidant proteins (i.e., CuZnSOD, MnSOD, EcSOD, NQO1, and GSTM1) in glycolytic muscles. Interestingly, skeletal muscle Nrf2 haplodeficiency blunted the increases of most of these proteins (i.e., CuZnSOD, EcSOD, and NQO1) suggesting that muscle p62 stimulates antioxidant protein expression also via additional, yet to be determined mechanisms. Of note, p62 gain‐of‐function mitigated glycolytic muscle wasting in LLC‐affected mice. Collectively, our findings identify skeletal muscle p62 as a potential therapeutic target for cancer cachexia.
Association of Admission Glucose and Outcomes After Endovascular Treatment for Acute Stroke: Data From the ANGEL-ACT Registry
Authors: Wang Xinyan , Liang Fa , Wu Youxuan , Jia Baixue , Zhang Yijun , Jian Minyu , Liu Haiyang , Wang Anxin , Han Ruquan , Miao Zhongrong
Published: August 2023

Background:

The association between admission glucose levels and clinical outcomes after stroke has not been effectively elucidated. This study assessed the association among admission glucose levels, admission hyperglycemia, diabetes mellitus, and 90-day neurological outcomes in patients with acute ischemic stroke undergoing endovascular therapy.

Methods:

The ANGEL-ACT registry enrolled adults with acute ischemic stroke undergoing endovascular therapy between 2017 and 2019 in China and patients with available admission glucose data were included. Restricted cubic spline regression was used to determine the knots of blood glucose levels. Binary or ordinal logistic regression models were used to examine the impact of different admission glucose levels on neurological outcomes and 90-day mortality.

Results:

In total, 1684 participants with available admission glucose concentrations were evaluated. The admission glucose level was divided into 4 levels according to the restricted cubic spline curves: level 1 (<5.3 mmol/L), level 2 (5.3 to 7.0 mmol/L), level 3 (7.0 to 11.6 mmol/L), and level 4 (≥11.6 mmol/L). Level 4 admission glucose was associated with a decreased incidence of a modified Rankin scale score of 0 to 2 (hazard ratio, 0.59; 95% CI, 0.40-0.87) and an increased risk of mortality (hazard ratio, 1.74; 95% CI, 1.06-2.85). Levels 3 and 4, hyperglycemia, and diabetes mellitus independently predicted symptomatic intracranial hemorrhage (sICH). Admission glucose levels showed J-shaped relationships with sICH.

Conclusions:

Higher admission glucose levels (≥11.6 mmol/L) were associated with a decreased likelihood of a modified Rankin scale score of 0 to 2 and an increased risk of mortality and sICH.
Are Patients With an International Classification of Diseases, 10th Edition Discharge Diagnosis Code for Sepsis Different in Regard to Demographics and Outcome Variables When Comparing Those With Sepsis Only to Those Also Diagnosed With COVID-19 or Those With a COVID-19 Diagnosis Alone?
Authors: Gaieski David F. , Tsukuda Jumpei , Maddox Parker , Li Michael
Published: August 2023

OBJECTIVES:

We analyzed whether patients with the International Classification of Diseases, 10th Edition (ICD-10) discharge diagnosis code for sepsis are different in regard to demographics and outcome variables when comparing those with sepsis only to those also diagnosed with COVID-19 or those with a COVID-19 diagnosis alone.

DESIGN:

Retrospective cohort study.

SETTING:

Nine hospitals in an academic health system.

PATIENTS:

Patients with a final ICD-10 discharge diagnostic code for sepsis only, a diagnosis of COVID-19-only, or a final sepsis ICD-10 discharge code + a diagnosis of COVID-19 admitted to the hospital were analyzed for demographic and outcome differences between the cohorts.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

A total of 11,395 patients met inclusion criteria: 6,945 patients (60.9%) were ICD-10 sepsis code only, 3,294 patients (28.9%) were COVID-19 diagnosis-only, and 1,153 patients (10.1%) were sepsis ICD-10 code + COVID-19 diagnosis. Comparing sepsis ICD-10 code + COVID-19 diagnosis patients to sepsis ICD-10 code only and COVID-19 diagnosis-only patients, the sepsis ICD-10 code + COVID-19 diagnosis patients were: older (69 [58–78] vs 67 [56–77] vs 64 [51–76] yr), less likely to be female (40.3% vs 46.7% vs 49.5%), more frequently admitted to the ICU (59.3% [684/1,153] vs 54.9% [1,810/3,297] vs 15% [1,042/6,945]), more frequently required ventilatory support (39.3% [453/1,153] vs 31.8% [1,049/3,297] vs 6.0% [417/6,945]), had longer median hospital length of stay (9 [5,16] vs 5 [3,8] vs 7. [4,13] d), and were more likely to die in the hospital (39.2% [452/1,153] vs 22.3% [735/3,297] vs 6.4% [444/6,945]).

CONCLUSIONS:

During the COVID-19 pandemic the sickest cohort of patients was those receiving an explicit ICD-10 code of sepsis + a COVID-19 diagnosis. A significant percentage of COVID-19 diagnosis-only patients appear to have been under-coded as they received a level of critical care (ICU admission; intubation) suggestive of the presence of acute organ dysfunction during their admission.
Facilitators and Barriers to Interacting With Clinical Decision Support in the ICU: A Mixed-Methods Approach
Authors: Wong Adrian , Berenbrok Lucas A. , Snader Lauren , Soh Yu Hyeon , Kumar Vishakha K. , Javed Muhammad Ali , Bates David W. , Sorce Lauren R. , Kane-Gill Sandra L.
Published: August 2023

OBJECTIVES:

Clinical decision support systems (CDSSs) are used in various aspects of healthcare to improve clinical decision-making, including in the ICU. However, there is growing evidence that CDSS are not used to their full potential, often resulting in alert fatigue which has been associated with patient harm. Clinicians in the ICU may be more vulnerable to desensitization of alerts than clinicians in less urgent parts of the hospital. We evaluated facilitators and barriers to appropriate CDSS interaction and provide methods to improve currently available CDSS in the ICU.

DESIGN:

Sequential explanatory mixed-methods study design, using the BEhavior and Acceptance fRamework.

SETTING:

International survey study.

PATIENT/SUBJECTS:

Clinicians (pharmacists, physicians) identified via survey, with recent experience with clinical decision support.

INTERVENTIONS:

An initial survey was developed to evaluate clinician perspectives on their interactions with CDSS. A subsequent in-depth interview was developed to further evaluate clinician (pharmacist, physician) beliefs and behaviors about CDSS. These interviews were then qualitatively analyzed to determine themes of facilitators and barriers with CDSS interactions.

MEASUREMENTS AND MAIN RESULTS:

A total of 48 respondents completed the initial survey (estimated response rate 15.5%). The majority believed that responding to CDSS alerts was part of their job (75%) but felt they experienced alert fatigue (56.5%). In the qualitative analysis, a total of five facilitators (patient safety, ease of response, specificity, prioritization, and feedback) and four barriers (excess quantity, work environment, difficulty in response, and irrelevance) were identified from the in-depth interviews.

CONCLUSIONS:

In this mixed-methods survey, we identified areas that institutions should focus on to improve appropriate clinician interactions with CDSS, specific to the ICU. Tailoring of CDSS to the ICU may lead to improvement in CDSS and subsequent improved patient safety outcomes.
Characteristics of Long-Stay Patients in a PICU and Healthcare Resource Utilization After Discharge
Authors: Boerman Gerharda H. , Haspels Heleen N. , de Hoog Matthijs , Joosten Koen F.
Published: August 2023

OBJECTIVES:

To examine the characteristics of long-stay patients (LSPs) admitted to a PICU and to investigate discharge characteristics of medical complexity among discharged LSP.

DESIGN:

We performed a retrospective cohort study where clinical data were collected on all children admitted to our PICU between July 1, 2017, and January 1, 2020.

SETTING:

A single-center study based at Erasmus MC Sophia Children’s Hospital, a level III interdisciplinary PICU in The Netherlands, providing all pediatric and surgical subspecialties.

PATIENTS:

LSP was defined as those admitted for at least 28 consecutive days.

INTERVENTIONS:

None.

MEASUREMENTS:

Length of PICU stay, diagnosis at admission, length of mechanical ventilation, need for extracorporeal membrane oxygenation, mortality, discharge location after PICU and hospital admission, medical technical support, medication use, and involvement of allied healthcare professionals after hospital discharge.

MAIN RESULTS:

LSP represented a small proportion of total PICU patients (108 patients; 3.2%) but consumed 33% of the total admission days, 47% of all days on extracorporeal membrane oxygenation, and 38% of all days on mechanical ventilation. After discharge, most LSP could be classified as children with medical complexity (CMC) (76%); all patients received discharge medications (median 5.5; range 2–19), most patients suffered from a chronic disease (89%), leaving the hospital with one or more technological devices (82%) and required allied healthcare professional involvement after discharge (93%).

CONCLUSIONS:

LSP consumes a considerable amount of resources in the PICU and its impact extends beyond the point of PICU discharge since the majority are CMC. This indicates complex care needs at home, high family needs, and a high burden on the healthcare system across hospital borders.
Precision medicine in extended adjuvant endocrine therapy for breast cancer
Authors: Tesch Megan E.
Published: August 2023

Purpose of review

In this review, the evolving role of currently available genomic assays for hormone receptor-positive, early-stage breast cancer in the selection of patients for extended adjuvant endocrine therapy will be discussed.

Recent findings

Several studies have investigated the prognostic performance of the Oncotype DX, Breast Cancer Index (BCI), Prosigna, and EndoPredict genomic assays in the late recurrence setting (>5 years after diagnosis), beyond standardly used clinicopathologic parameters, with mixed results. Recently, BCI has also been validated to predict the likelihood of benefit from extended endocrine therapy, though certain data limitations may need to be addressed to justify routine use in clinical practice.

Even after 5 years of adjuvant endocrine therapy, patients with hormone receptor-positive breast cancer have a significant risk for late recurrence, including distant metastases, that might be prevented with longer durations of endocrine therapy. However, the added toxicity and variable benefit derived from extended endocrine therapy make optimal patient selection crucial. Genomic assays are in development to risk-stratify patients for late recurrence and determine efficacy of extended endocrine therapy, with the aim to help guide extended endocrine therapy decisions for clinicians and individualize treatment strategies for patients.
Reconstitution of double-negative T cells after cord blood transplantation and its predictive value for acute graft-versus-host disease
Authors: Pan Tianzhong , Ding Peng , Huang Aijie , Tang Baolin , Song Kaidi , Sun Guangyu , Wu Yue , Yang Shiying , Chen Xingchi , Wang Dongyao , Zhu Xiaoyu
Published: August 2023

Background:

With an increasing number of patients with hematological malignancies being treated with umbilical cord blood transplantation (UCBT), the correlation between immune reconstitution (IR) after UCBT and graft-versus-host disease (GVHD) has been reported successively, but reports on double-negative T (DNT) cell reconstitution and its association with acute GVHD (aGVHD) after UCBT are lacking.

Methods:

A population-based observational study was conducted among 131 patients with hematological malignancies who underwent single-unit UCBT as their first transplant at the Department of Hematology, the First Affiliated Hospital of USTC, between August 2018 and June 2021. IR differences were compared between the patients with and without aGVHD.

Results:

The absolute number of DNT cells in the healthy Chinese population was 109 (70–157)/μL, accounting for 5.82 (3.98–8.19)% of lymphocytes. DNT cells showed delayed recovery and could not reach their normal levels even one year after transplantation. Importantly, the absolute number and percentage of DNT cells were significantly higher in UCBT patients without aGVHD than in those with aGVHD within one year (F = 4.684, P = 0.039 and F = 5.583, P = 0.026, respectively). In addition, the number of DNT cells in the first month after transplantation decreased significantly with the degree of aGVHD increased, and faster DNT cell reconstitution in the first month after UCBT was an independent protective factor for aGVHD (HR = 0.46, 95% confidence interval [CI]: 0.23–0.93; P = 0.031).

Conclusions:

Compared to the number of DNT cells in Chinese healthy people, the reconstitution of DNT cells in adults with hematological malignancies after UCBT was slow. In addition, the faster reconstitution of DNT cells in the early stage after transplantation was associated with a lower incidence of aGVHD.
Medications for alcohol use disorder promote abstinence in alcohol-associated cirrhosis: Results from a systematic review and meta-analysis
Authors: Gratacós-Ginès Jordi , Bruguera Pol , Pérez-Guasch Martina , López-Lazcano Ana , Borràs Roger , Hernández-Évole Helena , Pons-Cabrera Maria T. , Lligoña Anna , Bataller Ramón , Ginès Pere , López-Pelayo Hugo , Pose Elisa
Published: August 2023

Background and Aims:

The role of medications for alcohol use disorder (MAUD) in patients with cirrhosis is not well established. Evidence on the efficacy and safety of these drugs in these patients is scarce.

Approach and Results:

We performed a systematic review and meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol guidelines on the efficacy of MAUD in patients with cirrhosis. A search was conducted in PubMed, Embase, and Scopus, including all studies until May 2022. The population was defined as patients with AUD and cirrhosis. The primary outcome was alcohol abstinence. Safety was a secondary outcome. We performed a random-effect analysis and expressed the results as relative risk of alcohol consumption. Heterogeneity was measured by I
2. Out of 4095 unique references, 8 studies on 4 different AUD treatments [baclofen (n = 6), metadoxine (n = 1), acamprosate (n = 1), and fecal microbiota transplant (n = 1)] in a total of 794 patients were included. Four were cohort studies, and 4 were RCTs. Only RCTs were included in the meta-analysis. MAUD was associated with a reduced rate of alcohol consumption [relative risk = 0.68 (CI: 0.48–0.97), P = 0.03], increasing alcohol abstinence by 32% compared to placebo or standard treatment, despite high heterogeneity (I
2 = 67%). Regarding safety, out of 165 serious adverse events in patients treated with MAUD, only 5 (3%) were possibly or probably related to study medications.

Conclusion:

MAUD in patients with cirrhosis is effective in promoting alcohol abstinence and has a good safety profile. Larger studies on the effects of MAUD are needed, especially in patients with advanced liver disease.
Impact of PNPLA3 I148M on alpha-1 antitrypsin deficiency-dependent liver disease progression
Authors: Volkert Ines , Fromme Malin , Schneider Carolin , Candels Lena , Lindhauer Cecilia , Su Huan , Thorhauge Katrine , Pons Monica , Mohamed Mohamed Ramadan , Schneider Kai Markus , Strnad Pavel , Trautwein Christian
Published: August 2023

Background and Aims:

Genetic risk factors are major determinants of chronic liver disease (CLD) progression. Patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M polymorphism and alpha-1 antitrypsin (AAT) E342K variant, termed PiZ, are major modifiers of metabolic CLD. Both variants are known to affect metabolic CLD through increased endoplasmic reticulum stress, but their combined effect on CLD progression remains largely unknown. Here, we aimed to test our working hypothesis that their combined incidence triggers CLD disease progression.

Approach and Results:

We showed that patients with PiZZ/PNPLA3I148M from the European alpha-1-antitrypsin deficiency (AATD) liver consortium and the UK Biobank had a trend towards higher liver enzymes, but no increased liver fat accumulation was evident between subgroups. After generating transgenic mice that overexpress the PiZ variant and simultaneously harbor the PNPLA3I148M knockin (designated as PiZ/PNPLA3I148M), we observed that animals with PiZ and PiZ/PNPLA3I148M showed increased liver enzymes compared to controls during aging. However, no significant difference between PiZ and PiZ/PNPLA3I148M groups was observed, with no increased liver fat accumulation over time. To further study the impact on CLD progression, a Western-styled diet was administered, which resulted in increased fat accumulation and fibrosis in PiZ and PiZ/PNPLA3I148M livers compared to controls, but the additional presence of PNPLA3I148M had no impact on liver phenotype. Notably, the PiZ variant protected PNPLA3I148M mice from liver damage and obesity after Western-styled diet feeding.

Conclusion:

Our results demonstrate that the PNPLA3 polymorphism in the absence of additional metabolic risk factors is insufficient to drive the development of advanced liver disease in severe AATD.
Hepatocellular carcinoma reduced, HBsAg loss increased, and survival improved after finite therapy in hepatitis B patients with cirrhosis
Authors: Jeng Wen-Juei , Chien Rong-Nan , Chen Yi-Cheng , Lin Chih-Lang , Wu Chia-Ying , Liu Yen-Chun , Peng Chien-Wei , Su Chung-Wei , Hsu Cheng-Er , Liaw Yun-Fan
Published: August 2023

Background and Aims:

Long-term nucleos(t)ide analog (Nuc) treatment can reduce HCC in patients with HBV-related liver cirrhosis (HBV-LC). Earlier small cohort studies showed a comparable 5-year incidence of HCC in HBeAg-negative patients with HBV-LC who stopped and those continued Nuc therapy. This study aimed to validate these findings using a large cohort with 10-year follow-up.

Approach and Results:

From 2 centers, 494 HBeAg-negative patients with HBV-LC who stopped (finite group) and 593 who continued (continuous group) Nuc therapy were recruited. HCC, HBsAg loss, liver-related mortality/transplantation, and overall survival rates were compared between 2 groups with 1:1 propensity score matching of sex, treatment history, types of Nuc, age, transaminases, platelet count, and HBsAg levels at end of therapy in finite group or 3-year on-therapy in continuous groups. During a median follow-up of 6.2 (3.4–8.9) years, the annual and 10-year HCC incidence were lower in finite group (1.6 vs. 3.3%/y and 10-y 15.7% vs. 26.8%, respectively; log-rank test, p<0.0001). The finite group showed greater HBsAg decline/year (−0.116 vs. −0.095 log10 IU/mL, p=0.0026) and 7.6 times higher 10-year incidence of HBsAg loss (22.7% vs. 3%, p<0.0001). Multivariate Cox regression showed finite therapy an independent factor for HBsAg loss (adjusted HR: 11.79) but protective against HCC (adjusted HR: 0.593), liver-related mortality/transplantation (adjusted HR: 0.312), and overall mortality (adjusted HR: 0.382).

Conclusions:

Finite Nuc therapy in HBeAg-negative HBV-LC may reduce HCC incidence, increase HBsAg loss, and improve survival. Greater HBsAg decline/loss may reflect enhanced immunity and contribute to the reduction of hepatic carcinogenesis.
Review of Toxocariasis at a Children’s Hospital Prompting Need for Public Health Interventions
Authors: Fortini Mary B. , Erickson Timothy A. , Leining Lauren M. , Robinson Karina M. , Carey Megan N. , Smith Sarah J. , Sullivan Brendan , Nelson Alisa R. , Gunter Sarah M. , Weatherhead Jill E.
Published: August 2023

Background:

Toxocariasis, caused the by dog and cat roundworm, is one of the most common zoonotic helminth infections in the United States and can lead to severe lifelong morbidity in children. Although historical seroprevalence studies have identified a high frequency of toxocariasis regionally in the United States, there are few studies linking epidemiology and clinical disease in children. The study objective was to examine the contemporary epidemiology of pediatric toxocariasis within an endemic US region.

Methods:

We conducted an epidemiologic study analyzing children diagnosed with toxocariasis presenting to a tertiary pediatric hospital in Texas from 2010 to 2021. We examined risk factors and performed a geospatial analysis, including a comparative analysis of human cases and locations of surrendered infected stray animals in the same region.

Results:

Children diagnosed with toxocariasis were most commonly of Hispanic/Latino ethnicity (30/46; 65%), white race (41/45; 91%) and receiving Medicaid (34/44, 77%). Many infected children had contact with dogs or cats. Ocular toxocariasis was associated with a lack of peripheral eosinophilia (P < 0.001). No other Toxocara syndromes were associated with defined absolute eosinophil count levels. Post-treatment resolution of eosinophilia was variable, ranging from 1 to 172 weeks. A Toxocara hotspot was identified in northeast Houston, comprising one of the lowest median household incomes in the region.

Conclusions:

Toxocariasis is a devastating zoonotic infection in children living in the US. As it is not a reportable disease, the true burden remains unknown. It is critical to increase awareness of toxocariasis to direct public health interventions and ultimately reduce Toxocara-induced morbidity in US children.
DNA N6-methyladenine methylase N6AMT1 controls neuropathic pain through epigenetically modifying Kcnj16 in dorsal horn neurons
Authors: Zhou Hui-Min , Xu Heng-Jun , Sun Run-Hang , Zhang Ming , Li Xiao-Tong , Zhao Ya-Xuan , Yang Kehui , Wei Runa , Liu Qiaoqiao , Li Siyuan , Xue Zhouya , Hao Ling-Yun , Yang Li , Wang Qi-Hui , Wang Hong-Jun , Gao Fang , Cao Jun-Li , Pan Zhiqiang
Published: August 2023

Nerve injury–induced aberrant changes in gene expression in spinal dorsal horn neurons are critical for the genesis of neuropathic pain. N6-methyladenine (m6A) modification of DNA represents an additional layer of gene regulation. Here, we report that peripheral nerve injury significantly decreased the level of m6A-specific DNA methyltransferase 1 (N6amt1) in dorsal horn neurons. This decrease was attributed, at least partly, to a reduction in transcription factor Nr2f6. Rescuing the decrease in N6amt1 reversed the loss of m6A at the promoter for inwardly rectifying potassium channel subfamily J member 16 (Kcnj16), mitigating the nerve injury–induced upregulation of Kcnj16 expression in the dorsal horn and alleviating neuropathic pain hypersensitivities. Conversely, mimicking the downregulation of N6amt1 in naive mice erased DNA m6A at the Kcnj16 promoter, elevated Kcnj16 expression, and led to neuropathic pain–like behaviors. Therefore, decreased N6amt1 caused by NR2F6 is required for neuropathic pain, likely through its regulation of m6A-controlled KCNJ16 in dorsal horn neurons, suggesting that DNA m6A modification may be a potential new target for analgesic and treatment strategies.
Association of Work-Related Sedentary Behavior With Mental Health and Work Engagement Among Japanese White- and Blue-Collar Workers
Authors: Sakakibara Keiko , Miyanaka Daisuke , Tokita Masahito , Kawada Michiko , Mori Naana , Hamsyah Fuad , Lin Yuheng , Shimazu Akihito
Published: August 2023

Objective

This study investigated the association of work-related sedentary behavior with mental health and work engagement among white- and blue-collar workers.

Methods

An Internet survey was conducted among 1600 workers aged 20 to 59 years. A total of 1213 valid responses were analyzed to examine the association of work-related sedentary behavior with mental health and work engagement.

Results

Higher level of occupational sedentary behavior significantly associated with poorer mental health and lower work engagement among white-collar workers. Considering the effect of occupation, association of sedentary behavior with mental health disappeared, whereas association with work engagement remained for white-collar workers.

Conclusions

Our result suggested the importance of decreasing work-related sedentary behavior for enhancing work engagement regardless of the occupation for white-collar workers. Further study is needed to confirm the association between these variables for blue-collar workers.
Atherosclerosis on CT coronary angiography and the risk of long-term cardiovascular events after liver transplantation
Authors: Sampaio Rodrigues Thalys , Koshy Anoop N. , Gow Paul J. , Weinberg Laurence , Cailes Benjamin , Testro Adam , Smith Gerard , Lim Han S. , Teh Andrew W. , Lim Ruth P. , Farouque Omar
Published: August 2023

Computed tomography coronary angiography (CTCA) is increasingly utilized for preoperative risk stratification before liver transplantation (LT). We sought to assess the predictors of advanced atherosclerosis on CTCA using the recently developed Coronary Artery Disease-Reporting and Data System (CAD-RADS) score and its impact on the prediction of long-term major adverse cardiovascular events (MACE) following LT. We conducted a retrospective cohort study of consecutive patients who underwent CTCA for LT work-up between 2011 and 2018. Advanced atherosclerosis was defined as coronary artery calcium scores > 400 or CAD-RADS score ≥ 3 (≥50% coronary artery stenosis). MACE was defined as myocardial infarction, heart failure, stroke, or resuscitated cardiac arrest. Overall, 229 patients underwent CTCA (mean age 66 ± 5 y, 82% male). Of these, 157 (68.5%) proceeded with LT. The leading etiology of cirrhosis was hepatitis (47%), and 53% of patients had diabetes before transplant. On adjusted analysis, male sex (OR 4.6, 95% CI 1.5–13.8, p = 0.006), diabetes (OR 2.2, 95% CI 1.2–4.2, p = 0.01) and dyslipidemia (OR 3.1, 95% CI 1.3–6.9, p = 0.005) were predictors of advanced atherosclerosis on CTCA. Thirty-two patients (20%) experienced MACE. At a median follow-up of 4 years, CAD-RADS ≥ 3, but not coronary artery calcium scores, was associated with a heightened risk of MACE (HR 5.8, 95% CI 1.6–20.6, p = 0.006). Based on CTCA results, 71 patients (31%) commenced statin therapy which was associated with a lower risk of all-cause mortality (HR 0.48, 95% CI 0.24–0.97, p = 0.04). The standardized CAD-RADS classification on CTCA predicted the occurrence of cardiovascular outcomes following LT, with a potential to increase the utilization of preventive cardiovascular therapies.
Cultivating a Cycle of Positive Human Experience
Authors: Virkstis Katherine , Trepanier Sylvain
Published: August 2023

This article discusses the impact of the healthcare industry's workforce crisis on the patient experience and explores how technology can alleviate the pressure on patient care teams, reestablish the human connection between nurses and patients, and create a virtuous cycle in healthcare. By working together and leveraging digital solutions, healthcare organizations can develop more effective and efficient systems of care delivery that ultimately benefit both patients and care teams.
Application of Surgery Combined With Platelet-Rich Plasma in the Correction of Mild to Moderate Blepharoptosis
Authors: Gao Shenzhen , Li Changhao , Yi Min , Lu Baixue , Zhou Rong , Gao Weicheng
Published: August 2023

Objectives:

To explore the effect of surgery combined with platelet-rich plasma (PRP) in the correction of mild to moderate blepharoptosis.

Methods:

A retrospective study was conducted on 36 patients with bilateral mild to moderate blepharoptosis from January 2021 to January 2023, which were corrected by surgery combined with local multi-point injection of PRP. The postoperative effect was observed, and the incidence of postoperative complications and patient satisfaction were calculated.

Results:

Postoperative follow-up was 3 months to 2 years. Thirty-five cases of blepharoptosis were well corrected; 1 case (2.8%) had insufficient correction and was corrected by reoperation. There were no obvious complications such as incomplete closure, conjunctival prolapse, and exposed keratitis in 36 patients. All patients were satisfied.

Conclusion:

Surgery combined with PRP is effective in the correction of mild to moderate blepharoptosis with few complications and high satisfaction. As far as we know, this is the first time to apply PRP in the correction of blepharoptosis, which may provide a new idea for the clinical treatment of blepharoptosis and is worth popularizing.
Meningomyelocele Reconstruction: Comparison of Repair Methods via Systematic Review
Authors: Leach Garrison A. , Pflibsen Lacey R. , Roberts Alexis-Danielle , O’Connor Madeline J. , Bristol Ruth E. , Mabee Melinda K. , Almader-Douglas Diana , Schaub Timothy A.
Published: August 2023

Purpose:

The purpose of this article was to appraise the various methods of reconstruction for meningomyelocele (MMC) defects.

Methods:

A systematic review of the literature was performed to evaluate all reconstructions for MMC. The method of reconstruction was categorized by: primary closure with and without fascial flaps, random pattern flaps, VY advancement flaps (VY), perforator flaps, and myocutaneous flaps. Perforator flaps were subsequently subcategorized based on the type of flap.

Results:

Upon systematic review, 567 articles were screened with 104 articles assessed for eligibility. Twenty-nine articles were further reviewed and included for qualitative synthesis. Two hundred seventy patients underwent MMC repair. The lowest rates of major wound complications (MWC) were associated with myocutaneous and random pattern flaps. A majority of MWC was in the lumbrosacral/sacral region (87.5% of MWC). In this region, random patterns and perforator flaps demonstrated the lowest rate of MWC (4.5, 8.1%).

Conclusions:

Plastic surgery consultation should be strongly considered for MMC with defects in the lumbosacral/sacral region. Perforator flaps are excellent options for the reconstruction of these defects.
Modified Alar Base Reduction: A Novel Technique
Authors: Khan Mohammed A. , Jomah Mohammed , Assiri Hassan , Alolaywi Ahmed , Alarfaj Ahmed
Published: August 2023

Background:

Alar base reduction (ABR) surgery is one of the rhinoplasty techniques used to reduce alar flaring, nasal base width, or both. It is crucial for rhinoplasty surgeons to understand and analyze the type of nasal base deformity to achieve satisfactory results and avoid complications.

Objectives:

The objective of this study is to describe a novel technique of ABR that addresses alar flaring while avoiding violation of the nostril marginal rim.

Methods:

This prospective cohort study included patients with alar flaring who underwent rhinoplasty or septorhinoplasty with ABR using our modified technique. Demographic data, clinical history, aesthetic concerns, and preoperative and postoperative photographs were collected for each patient. The surgical outcome was assessed using subjective scar evaluation scores at 3 and 6 months, the Stony Brook Scar Evaluation Scale at 6 months, and an overall appearance satisfaction score.

Results:

A total of 8 patients were included in the study. Subjectively, the majority of patients (75%) reported satisfactory scar appearance at the 6-month follow-up. The mean Stony Brook score was 4.7 (SD=0.74). Nostril symmetry was achieved in all patients. Seventy-five percent of the participants expressed satisfaction with the overall appearance.

Conclusions:

Our modified ABR technique demonstrates promising results in correcting alar flaring while achieving nostril symmetry with an acceptable scar. Further studies with a larger sample size are needed to evaluate the feasibility of the technique and compare it to other classical techniques.

Level of Evidence:

Level IV.
Using facial reaction analysis and machine learning to objectively assess palatability of medicines in children
Authors: Aziza Rabia , Alessandrini Elisa , Matthews Clare , Ranmal Sejal , Zhou Ziyu , Davies Elin Haf , Tuleu Catherine
Published: August 2023

For orally administered drugs, palatability is key in ensuring patient acceptability and treatment compliance. Therefore, understanding children’s taste sensitivity and preferences can support formulators in making paediatric medicines more acceptable. Presently, we explore if the application of computer-vision techniques to videos of children’s reaction to gustatory taste strips can provide an objective assessment of palatability.

Primary school children tasted four different flavoured strips: no taste, bitter, sweet and sour. Data was collected at home, under the supervision of a guardian, with responses recorded using the Aparito Atom5™ app and smartphone camera. Participants scored each strip on a 5-point hedonic scale. Facial landmarks were identified in the videos, and quantitative measures such as changes around the eyes, nose and mouth were extracted to train models to classify strip taste and score. We received 197 videos and 256 self-reported scores from 64 participants. The hedonic scale elicited expected results: children like sweetness, dislike bitterness and have varying opinions for sourness. The findings revealed the complexity and variability of facial reactions and highlighted specific measures, such as eyebrow and mouth corner elevations, as significant indicators of palatability. This study into children’s taste specificities can improve the measurement of paediatric medicine acceptability. An objective measure of how children feel about the taste of medicines has great potential in helping find the most palatable formulation. Moreover, collecting data in the home setting allows for natural behaviour, with minimal burden for participants.

Author summary

When formulating medicines for children, understanding the taste profile is crucial to ensure they are not excessively unpleasant. In this study, we assessed if facial reactions in response to taste stimuli can be used to easily measure children’s feelings about the taste. We recorded videos of children trying different taste strips and analysed their facial expressions in response to each taste. The strips had different flavours: bitter, sweet, sour, and one with no taste. We also asked the children to rate each strip on scale of 1 to 5. We collected data from 64 children. The results confirmed that children generally like sweet tastes and do not like bitter ones. Their opinions on sour taste varied. Moreover, we found that specific facial reactions, like changes in their eyebrows and mouth corners were good indicators of taste preferences. The analysis of facial expressions can help formulators make medicines for children taste better. By objectively measuring how children feel about the taste of medicines, we can create more acceptable medicines for them. The collection of this data at home ensured children were in their comfortable environment, making it easier for them to be part of the study.
Liver fibrosis assessed using non-invasive markers and genetic polymorphisms (PNPLA3andTM6SF2) predisposing to liver fibrosis, is associated with hospitalization or death from heart failure: a prospective UK Biobank study
Authors: Hydes Theresa J , Kennedy Oliver J , Glyn-Owen Kate , Buchanan Ryan , Parkes Julie , Cuthbertson Daniel J , Roderick Paul , Byrne Christopher D
Published: August 2023

Background

Aside from liver related complications, non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ArLD) are associated with an increased risk of cardiovascular disease (CVD). Liver fibrosis, determined via histology and non-invasive serum fibrosis markers, is associated with cardiovascular events. The association between liver fibrosis and heart failure, and the relationship betweenPNPLA3rs738409 andTM6SF2rs58542926 and heart failure is of particular interest, given the known associations of these genetic polymorphisms with increased risk of liver fibrosis and decreased risk of coronary artery disease.

Methods

Using data from the UK Biobank (UKBB), we examined the relationship between liver fibrosis, determined using non-invasive markers (NAFLD fibrosis score, Fibrosis-4 (FIB-4) and AST to platelet ratio index (APRI score)) and hospitalization or death from heart failure in 413,860 people. Participants were followed up prospectively via electronic linkage to hospital and death records. Cox-regression estimated the hazard ratios (HR) for death or admission with heart failure. The effects ofPNPLA3andTM6SF2on the association between liver fibrosis and incident heart failure were estimated in an analysis stratified by genotype and by testing for an interaction between genotype and liver fibrosis using a likelihood ratio test.

Results

12,527 incident cases of heart failure occurred over a median of 10.7 years. Liver fibrosis, determined by single or combination non-invasive tests, was associated with an increased risk of hospitalization or death from heart failure; multivariable adjusted high risk NFS score HR 1.59 [1.45-1.76], p<0.0001, FIB-4 HR 1.69 [1.55-1.84], p<0.0001, APRI HR 1.85 [1.56-2.19], p<0.0001, combined fibrosis scores HR 1.90 [1.44-2.49], p<0.0001). These associations persisted for people with NAFLD or harmful alcohol consumption. Polymorphisms linked to liver fibrosis (PNPLA3rs738409 GG andTM6SF2rs58542926 TT) further amplified the positive association between non-invasive liver fibrosis markers and heart failure. A statistically significant interaction was found betweenPNPLA3rs738409, FIB-4, APRI score and heart failure.

Conclusion

Liver fibrosis, determined via non-invasive tests, is associated with an increased risk of hospitalization/death from heart failure in a general population cohort with mixed etiologies of chronic liver disease, including individuals with NAFLD and harmful alcohol consumption. Genetic polymorphisms associated with increased risk of liver fibrosis further increased the risk of heart failure. These findings have important mechanistic, clinical, and public health implications.