bluuebunny/crossref_metadata_2025 huggingface dataset:
Is it possible to automate the discovery of process maps for the time-driven activity-based costing method? A systematic review
Authors: Iachecen Franciele , Dallagassa Marcelo Rosano , Portela Santos Eduardo Alves , Carvalho Deborah Ribeiro , Ioshii Sérgio Ossamu
Published: December 2023

Objectives

The main objective of this manuscript was to identify the methods used to create process maps for care pathways that utilized the time-driven activity-based costing method.

Methods

This is a systematic mapping review. Searches were performed in the Embase, PubMed, CINAHL, Scopus, and Web of Science electronic literature databases from 2004 to September 25, 2022. The included studies reported practical cases from healthcare institutions in all medical fields as long as the time-driven activity-based costing method was employed. We used the time-driven activity-based costing method and analyzed the created process maps and a qualitative approach to identify the main fields.

Results

A total of 412 studies were retrieved, and 70 articles were included. Most of the articles are related to the fields of orthopedics and childbirth-related to hospital surgical procedures. We also identified various studies in the field of oncology and telemedicine services. The main methods for creating the process maps were direct observational practices, complemented by the involvement of multidisciplinary teams through surveys and interviews. Only 33% of the studies used hospital documents or healthcare data records to integrate with the process maps, and in 67% of the studies, the created maps were not validated by specialists.

Conclusions

The application of process mining techniques effectively automates models generated through clinical pathways. They are applied to the time-driven activity-based costing method, making the process more agile and contributing to the visualization of high degrees of variations encountered in processes, thereby making it possible to enhance and achieve continual improvements in processes.
Postmortem minimally invasive tissue sampling in communities: exploring perceptions of families, funeral workers, religious and community leaders and healthcare providers from Pakistan
Authors: Ahsan Nazia , Malik Fauzia Aman , Mughis Waliyah , Jabeen Rawshan , Mehboob Shaheen , Allana Raheel , Quratulain Syeda , Jamal Saima , Paganelli Christina R. , Goco Norman , Parlberg Lindsay , Omer Saad B. , Kazi Abdul Momin
Published: December 2023

Background

Minimally invasive tissue sampling (MITS) has increasingly been used to improve the diagnosis of disease and identification of the cause of death, particularly in underserved areas. However, there are multiple barriers to accessing those who die within the community, our study aimed to explore the perceptions and insights of community members and healthcare providers regarding the feasibility of implementing MITS in community settings.

Methods

A qualitative exploratory study was conducted. A total of twenty one in-depth interviews were conducted with deceased infants’ parents, elders of the family, religious leaders, community leaders, and funeral workers. Focus group discussions were conducted with health care providers (n = 14) in two peri-urban slum areas of Karachi, Pakistan. The duration of this study was from August to October 2020. Data was analyzed using thematic analysis and was coded and merged into categories forming eight major themes.

Results

In general, participants viewed minimally invasive tissue sampling (MITS) as beneficial for improving child health, though some had concerns about disrespecting the deceased during sample collection. Misinformation, fear of needles, and medical procedures were major barriers to MITS implementation. To enhance acceptance, community and religious leaders suggested using religious rulings, obtaining parental consent, ensuring confidentiality, and increasing efforts of community engagement. Community healthcare providers, along with funeral workers, recommended providing community members with grief counseling to increase study participation. Besides concerns about sampling interfering with respect for the decease, community members also raised concerns about misinformation. Further, participants provided feedback on the design and appearance of the mobile van used to collect MITS samples from children under the age of five.

Conclusion

This study is critical for understanding the challenges associated with implementation of community-based MITS sampling in Pakistan. Integrating the use of a mobile van for sample collection, grief counseling along with community engagement sessions and advocacy will help address community-based misinformation and develop community trust.
Follow-up non-attendance after long-bone fractures in a low-resource setting: a prospective study of predictors and interventions to increase attendance rates
Authors: Adesina Stephen Adesope , Amole Isaac Olusayo , Akinwumi Akinsola Idowu , Adegoke Adepeju Olatayo , Durodola Adewumi Ojeniyi , Owolabi James Idowu , Awotunde Olufemi Timothy , Adefokun Imri Goodness , Ojo Simeon Ayorinde , Eyesan Samuel Uwale
Published: December 2023

Background

While the majority of traumatic injuries occur in low- and middle-income countries, the published literature comes chiefly from high-income countries due to poor follow-up. Clinical and radiographic post-surgical trauma follow-up is essential to high-quality research and objective monitoring for healing and/or complications. This study aimed to identify the predictors of follow-up non-attendance in a low-resource setting and investigate the extent to which interventional efforts based on mobile phone technology (MPT) and home visits improved the follow-up rates for fractures treated with SIGN nails.

Methods

This was a prospective study of 594 patients with long-bone fractures. Socio-demographic (e.g. age, gender, marital status, education level, etc.) and clinical (e.g. fracture type, concomitant injuries, comorbidity, etc.) data were collected on each patient. Before discharge, the importance of follow-up was explained to patients and their relations. They were encouraged to attend even if they felt well. Their residential addresses and telephone numbers were validated and securely stored. Patients who missed their appointments were contacted by phone. Those who failed to honour 2 or 3 rescheduled appointments were visited in their home. The patients were divided into those who returned for the primarily scheduled follow-up without prompting (volition group) and those who did not come (non-attenders). Univariate analyses and binary logistic regression were conducted to determine the significant predictors of non-attendance.

Results

The proportion of patients in the volition group reduced from 96.1% at 6 weeks to 53.0% at 12 weeks and 39.2% at 6 months. However, interventional efforts increased these values to 98.5%, 92.5%, and 72.4% respectively. Walking unaided before the primarily scheduled 12-week appointment was the major reason for not attending the follow-up. Education, occupation, post-operative length of hospital stay (PLOS) and infection were significantly associated with non-attendance but younger age, long distances from the hospital, being separated or divorced, difficulty paying the in-patient care bill, closed fracture, having no (or a non-limb) concomitant injury, achieving painless weight bearing ≤ 6 weeks post-operatively and needing no additional surgery were independent predictors of non-attendance.

Conclusions

Our study sheds light on the predictors of follow-up non-attendance and demonstrates how interventional efforts improved attendance rates in a low-resource setting. In addition, efforts that better the socio-economic status of people such as more-encompassing health insurance coverage and greater work flexibility can improve the follow-up attendance rates.
Exploring multimorbidity profiles in middle-aged inpatients: a network-based comparative study of China and the United Kingdom
Authors: Bao Yining , Lu Pengyi , Wang Mengjie , Zhang Xueli , Song Aowei , Gu Xiaoyun , Ma Ting , Su Shu , Wang Lin , Shang Xianwen , Zhu Zhuoting , Zhai Yuhang , He Mingguang , Li Zengbin , Liu Hanting , Fairley Christopher K. , Yang Jiangcun , Zhang Lei
Published: December 2023

Background

Multimorbidity is better prevented in younger ages than in older ages. This study aims to identify the differences in comorbidity patterns in middle-aged inpatients from China and the United Kingdom (UK).

Methods

We utilized 184,133 and 180,497 baseline hospitalization records in middle-aged populations (40–59 years) from Shaanxi, China, and UK Biobank. Logistic regression was used to calculate odds ratios and P values for 43,110 unique comorbidity patterns in Chinese inpatients and 21,026 unique comorbidity patterns in UK inpatients. We included the statistically significant (P values adjusted by Bonferroni correction) and common comorbidity patterns (the pattern with prevalence > 1/10,000 in each dataset) and employed network analysis to construct multimorbidity networks and compare feature differences in multimorbidity networks for Chinese and UK inpatients, respectively. We defined hub diseases as diseases having the top 10 highest number of unique comorbidity patterns in the multimorbidity network.

Results

We reported that 57.12% of Chinese inpatients had multimorbidity, substantially higher than 30.39% of UK inpatients. The complete multimorbidity network for Chinese inpatients consisted of 1367 comorbidities of 341 diseases and was 2.93 × more complex than that of 467 comorbidities of 215 diseases in the UK. In males, the complexity of the multimorbidity network in China was 2.69 × more than their UK counterparts, while the ratio was 2.63 × in females. Comorbidities associated with hub diseases represented 68.26% of comorbidity frequencies in the complete multimorbidity network in Chinese inpatients and 55.61% in UK inpatients. Essential hypertension, dyslipidemia, type 2 diabetes mellitus, and gastritis and duodenitis were the hub diseases in both populations. The Chinese inpatients consistently demonstrated a higher frequency of comorbidities related to circulatory and endocrine/nutritional/metabolic diseases. In the UK, aside from these comorbidities, comorbidities related to digestive and genitourinary diseases were also prevalent, particularly the latter among female inpatients.

Conclusions

Chinese inpatients exhibit higher multimorbidity prevalence and more complex networks compared to their UK counterparts. Multimorbidity with circulatory and endocrine/nutritional/metabolic diseases among both Chinese and UK inpatients necessitates tailored surveillance, prevention, and intervention approaches. Targeted interventions for digestive and genitourinary diseases are warranted for the UK.
Triglyceride-glucose index is associated with a higher risk of stroke in a hypertensive population
Authors: Zhang Nan , Chi Xiying , Zhou Ziyi , Song Yun , Li Shuqun , Xu Jiafeng , Li Jianping
Published: December 2023

Background

This study aimed to evaluate the association of triglyceride-glucose (TyG) index, an insulin resistance surrogate biomarker, with first stroke in a hypertensive population and to explore potential influencing factors.

Methods

This study, a cohort study among a rural Chinese hypertensive population, utilized data from the China Stroke Primary Prevention Trial (CSPPT). The TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Multivariate analysis using Cox proportional hazards models was conducted.

Results

A total of 7569 hypertensive patients were included in this study. When TyG index was assessed as quartiles, compared with the reference group (Quartile 1), the hazard ratio of stroke was 1.04 in Quartile 2, 1.43 in Quartile 3, and 1.45 in Quartile 4, with a significant trend test (P = 0.013). When Quartiles 3 and 4 were combined (≥ 8.8), the hazard ratio was 1.41 compared with combined Quartiles 1 and 2 (< 8.8). Similar findings were observed for the association of TyG index with ischemic stroke. Further, a joint effect of baseline TyG index and age on first stroke was found. Using the group with TyG < 8.8 and age < 60 years as a reference, the highest hazard ratio of stroke was found in the group with a higher TyG index and aged 60 or greater (HR: 2.15, 95% CI 1.50, 3.07, P < 0.001).

Conclusions

In a hypertensive population, baseline TyG index was associated with a significantly higher risk of first stroke. In addition, age was a significant effect modifier for this association.
Hsa_circ_0136666 stimulates gastric cancer progression and tumor immune escape by regulating the miR-375/PRKDC Axis and PD-L1 phosphorylation
Authors: Miao Zhenyan , Li Jifei , Wang Yu , Shi Mingqin , Gu Xiao , Zhang Xuanqi , Wei Fang , Tang Xinying , Zheng Lufeng , Xing Yingying
Published: December 2023

Background

Targeted drugs are not quite effective for prolonging the survival of patients with gastric cancer due to off-target effects as well as tumor immune escape mechanisms. Circular RNAs widely exist in tumor regions as biomarkers and can be developed as effective drug targets.

Methods

Western blot, QRT-PCR, fluorescence in situ hybridization, and flow cytometry were used to investigate the function of hsa_circ_0136666 in promoting the proliferation of gastric cancer cells. Tissue immunofluorescence, enzyme-linked immunosorbent assay (ELISA), as well as flow cytometric analysis, was conducted to explore the process of tumor immune evasion in tumor-bearing mice. The differences of circRNA expression in clinical samples were analyzed through tissue microarray FISH. The effect of siRNA on improving the efficacy of anti-PDL1 drugs and suppressing the immune microenvironment was evaluated by the coadministration model.

Results

We demonstrated that hsa_circ_0136666 was widely and highly expressed in gastric cancer tissues and cells. Functionally, hsa_circ_0136666 promoted gastric cancer tumor proliferation and tumor microenvironment formation, leading to tumorigenesis immune escape, and this effect was dependent on CD8 + T cells. Mechanistically, we confirmed that hsa_circ_0136666 competitively upregulated PRKDC expression by sponging miR-375-3p, regulating immune checkpoint proteins, prompting phosphorylation of PD-L1 to preventing its degradation, driving PD-L1 aggregation and suppressing immune function, thereby impairing cancer immune responses. In terms of application, we found that LNP-siRNA effectively improved anti-PDL1 drug efficacy and inhibited immune escape.

Conclusion

Our results reveal an oncogenic role played by hsa_circ_0136666 in gastric cancer, driving PD-L1 phosphorylation via the miR-375/PRKDC signaling axis, prompting immune escape. This work proposes a completely new pathogenic mechanism of gastric cancer, uncovers a novel role for hsa_circ_0136666 as an immune target, and provides a rationale for enhancing the efficacy of anti-PD-L1 therapy for gastric cancer.
Suramin, an antiparasitic drug, stimulates adipocyte differentiation and promotes adipogenesis
Authors: Li Hanxiao , Dong Yingyue , Han Chunmiao , Xia Lisha , Zhang Yue , Chen Tongsheng , Wang Huamin , Xu Guoheng
Published: December 2023

Background

Previous studies demonstrated that mast cells with their degranulated component heparin are the major endogenous factors that stimulate preadipocyte differentiation and promote fascial adipogenesis, and this effect is related to the structure of heparin. Regarding the structural and physiological properties of the negatively charged polymers, hexasulfonated suramin, a centuries-old medicine that is still used for treating African trypanosomiasis and onchocerciasis, is assumed to be a heparin-related analog or heparinoid. This investigation aims to elucidate the influence of suramin on the adipogenesis.

Methods

To assess the influence exerted by suramin on adipogenic differentiation of primary white adipocytes in rats, this exploration was conducted both in vitro and in vivo. Moreover, it was attempted to explore the role played by the sulfonic acid groups present in suramin in mediating this adipogenic process.

Results

Suramin demonstrated a dose- and time-dependent propensity to stimulate the adipogenic differentiation of rat preadipocytes isolated from the superficial fascia tissue and from adult adipose tissue. This stimulation was concomitant with a notable upregulation in expression levels of pivotal adipogenic factors as the adipocyte differentiation process unfolded. Intraperitoneal injection of suramin into rats slightly increased adipogenesis in the superficial fascia and in the epididymal and inguinal fat depots. PPADS, NF023, and NF449 are suramin analogs respectively containing 2, 6, and 8 sulfonic acid groups, among which the last two moderately promoted lipid droplet formation and adipocyte differentiation. The number and position of sulfonate groups may be related to the adipogenic effect of suramin.

Conclusions

Suramin emerges as a noteworthy pharmaceutical agent with the unique capability to significantly induce adipocyte differentiation, thereby fostering adipogenesis.
Body-weight support gait training in neurological intensive care: safety, feasibility, and delays before walking with or without suspension
Authors: Jourdan Claire , Pradalier Fanny , Chalard Kevin , Ascher Margrit , Miron Duran Francisco , Pavillard Frédérique , Greco Frédéric , Mellouk Myriam , Fournier Stéphane , Djanikian Flora , Laffont Isabelle , Gelis Anthony , Perrigault Pierre-François
Published: December 2023

Background

Early Mobilization in Intensive Care Units (ICUs) enhances patients’ evolution, but has been rarely studied in neurological ICUs. The aim of this study was to assess gait training with body-weight support (BWS) in neuroICU, and to report on its safety, feasibility and on delays before walking with and without BWS.

Methods

This study was an observational one-year single-center study. Inclusion criteria were adults with a neurological injury requiring mechanical ventilation. Exclusion criteria were early death or ICU transfer. After weaning from ventilation, patients were screened for indications of BWS walking using predefined criteria.

Results

Patients’ conditions were mostly brain injuries: 32% subarachnoid hemorrhages, 42% focal strokes, and 12% traumatic brain injuries. Out of 272 admissions, 136 patients were excluded, 78 were eligible, and 33 performed BWS walking. Among non-eligible patients, 36 walked unsuspended upon ventilation weaning, 17 presented too severe impairments. Among the 45 eligible patients who did not receive BWS training, main reasons were workload and weekends (31%), medical barriers (29%), and early ICU discharge (22%). 78 BWS sessions were performed on the 33 beneficiaries (median sessions per patient 2, max 10). Pre-session, most patients had inadequate response to pain, orders, or simple orientation questions. Sitting without support was impossible for 74%. Most pre-post changes in hemodynamic, respiratory, and pain parameters were small, and recovered spontaneously after the session. Eight sessions were interrupted; reasons were pain, fatigue or major imbalance (4), syncope (1), occurrence of stool (2), and battery failure (1). None of these adverse events required medical intervention, patients recovered upon session interruption. Median session duration was 31 min, patients walked on median 17 m. First BWS session occurred on median 3 days after ventilation weaning, and 11 days before patients were able to walk unsuspended.

Conclusions

Verticalization and walking using a suspension device in patients in neuroICU allows early gait training, despite challenging neurological impairments. It is safe and generally well tolerated.

Trial registration: ClinicalTrials database (ID: NCT04300491).
Towards a multidimensional measure of well-being: cross-cultural support through the Italian validation of the well-being profile
Authors: Scalas L. Francesca , Lodi Ernesto , Magnano Paola , Marsh Herbert W.
Published: December 2023

Background

The Well-being Profile (WB-Pro) is a multi-item and multidimensional instrument with strong psychometric properties and a solid theoretical grounding. It includes aspects of hedonic and eudaimonic well-being that can be used at the individual and social levels.

Method

We developed the Italian version through back-translation procedures. The aim of this study is to validate the WB-Pro in Italian as well as to better understand its multidimensionality through bifactor analysis. A sample of 1451 participants (910 = women, 62.7%; age range: 18–70, M-age = 32.34, SD-age = 13.64) was involved.

Results

The 15-factor structure was confirmed with CFA and ESEM and was invariant across gender, age, and education. We examined convergent and discriminant validity and a bifactorial representation. Short versions of the WB-Pro were tested.

Discussion

Even though a few items of the Italian version of the WB-Pro might benefit from revision (e.g., clear-thinking scale), this study confirms the theoretical and empirical strength of the WB-Pro.

Conclusions

This study supports the WB-Pro validity and usefulness in studying well-being and for professional psychological applications to assess well-being in both individuals and groups.
Host microbiome associated low intestinal acetate correlates with progressive NLRP3-dependent hepatic-immunotoxicity in early life microcystin-LR exposure
Authors: More Madhura , Chatterjee Somdatta , Saha Punnag , Bose Dipro , Trivedi Ayushi , Roy Subhajit , Chatterjee Saurabh
Published: December 2023

Background

Microcystins (MCs), potent hepatotoxins pose a significant health risk to humans, particularly children, who are more vulnerable due to higher water intake and increased exposure during recreational activities.

Methods

Here, we investigated the role of host microbiome-linked acetate in modulating inflammation caused by early-life exposure to the cyanotoxin Microcystin-LR (MC-LR) in a juvenile mice model.

Results

Our study revealed that early-life MC-LR exposure disrupted the gut microbiome, leading to a depletion of key acetate-producing bacteria and decreased luminal acetate concentration. Consequently, the dysbiosis hindered the establishment of a gut homeostatic microenvironment and disrupted gut barrier function. The NOD-like receptor family pyrin domain – containing 3 (NLRP3) inflammasome, a key player in MC-induced hepatoxicity emerged as a central player in this process, with acetate supplementation effectively preventing NLRP3 inflammasome activation, attenuating hepatic inflammation, and decreasing pro-inflammatory cytokine production. To elucidate the mechanism underlying the association between early-life MC-LR exposure and the progression of metabolic dysfunction associated steatotic liver disease (MASLD), we investigated the role of acetate binding to its receptor -G-protein coupled receptor 43 (GPR43) on NLRP3 inflammasome activation. Our results demonstrated that acetate-GPR43 signaling was crucial for decreasing NLRP3 protein levels and inhibiting NLRP3 inflammasome assembly. Further, acetate-induced decrease in NLRP3 protein levels was likely mediated through proteasomal degradation rather than autophagy. Overall, our findings underscore the significance of a healthy gut microbiome and its metabolites, particularly acetate, in the progression of hepatotoxicity induced by early life toxin exposure, crucial for MASLD progression.

Conclusions

This study highlights potential therapeutic targets in gut dysbiosis and NLRP3 inflammasome activation for mitigating toxin-associated inflammatory liver diseases.
ApoER2-Dab1 disruption as the origin of pTau-associated neurodegeneration in sporadic Alzheimer’s disease
Authors: Ramsden Christopher E. , Zamora Daisy , Horowitz Mark S. , Jahanipour Jahandar , Calzada Elizabeth , Li Xiufeng , Keyes Gregory S. , Murray Helen C. , Curtis Maurice A. , Faull Richard M. , Sedlock Andrea , Maric Dragan
Published: December 2023

In sporadic Alzheimer’s disease (sAD) specific regions, layers and neurons accumulate hyperphosphorylated Tau (pTau) and degenerate early while others remain unaffected even in advanced disease. ApoER2-Dab1 signaling suppresses Tau phosphorylation as part of a four-arm pathway that regulates lipoprotein internalization and the integrity of actin, microtubules, and synapses; however, the role of this pathway in sAD pathogenesis is not fully understood. We previously showed that multiple ApoER2-Dab1 pathway components including ApoE, Reelin, ApoER2, Dab1, pP85αTyr607, pLIMK1Thr508, pTauSer202/Thr205 and pPSD95Thr19 accumulate together within entorhinal-hippocampal terminal zones in sAD, and proposed a unifying hypothesis wherein disruption of this pathway underlies multiple aspects of sAD pathogenesis. However, it is not yet known whether ApoER2-Dab1 disruption can help explain the origin(s) and early progression of pTau pathology in sAD. In the present study, we applied in situ hybridization and immunohistochemistry (IHC) to characterize ApoER2 expression and accumulation of ApoER2-Dab1 pathway components in five regions known to develop early pTau pathology in 64 rapidly autopsied cases spanning the clinicopathological spectrum of sAD. We found that (1) these selectively vulnerable neuron populations strongly express ApoER2; and (2) multiple ApoER2-Dab1 components representing all four arms of this pathway accumulate in abnormal neurons and neuritic plaques in mild cognitive impairment (MCI) and sAD cases and correlate with histological progression and cognitive deficits. Multiplex-IHC revealed that Dab1, pP85αTyr607, pLIMK1Thr508, pTauSer202/Thr205 and pPSD95Thr19 accumulate together within many of the same ApoER2-expressing neurons and in the immediate vicinity of ApoE/ApoJ-enriched extracellular plaques. Collective findings reveal that pTau is only one of many ApoER2-Dab1 pathway components that accumulate in multiple neuroanatomical sites in the earliest stages of sAD and provide support for the concept that ApoER2-Dab1 disruption drives pTau-associated neurodegeneration in human sAD.
Maternal–child consumption of ultra-processed foods and sugar-sweetened beverages in informal settlements in Mumbai, India
Authors: Kumar Aarti , Kulchar Rachel J. , Khadka Nehaa , Smith Charlotte , Mukherjee Piyasree , Rizal Erika , Sokal-Gutierrez Karen
Published: December 2023

Background

The global nutrition transition is associated with increased consumption of ultra-processed snack foods and sugar-sweetened beverages (UPF/SSB), contributing to the double burden of child obesity and undernutrition.

Methods

This cross-sectional study describes the prevalence of maternal and child UPF/SSB consumption and the factors associated with frequent consumption in a convenience sample of 749 children ages 6 months through 6 years and their mothers participating in a community-based child oral health program in five informal settlement communities in Mumbai, India. Mothers were interviewed regarding maternal and child oral health and nutrition characteristics, including consumption of beverages and foods associated with tooth decay—milk, soda, tea with sugar, sweets, and chips/biscuits—using standardized questionnaires. Spearman correlations were used to assess for associations between various social factors and the frequency of maternal and child consumption of the five food categories. Chi-square tests were used to assess differences in child consumption patterns by age groups.

Results

Though reported soda consumption was low among both mothers and children, nearly 60% of children consumed sweets and chips/biscuits daily, four to five times the rate of mothers. Factors associated with children’s frequent consumption of UPF/SSB included lower maternal education level, frequent maternal consumption of UPF/SSB, greater number of household members, greater amount of money given to the child, and closer proximity to a store.

Conclusion

Our findings demonstrate social factors that may promote UPF/SSB consumption. The nutritional dangers of sugary drinks and non-nutritious snacks for mothers and young children should be addressed across maternal–child health, education, and social service programs. Early childhood nutrition interventions should involve the entire family and community and emphasize the need to limit children’s consumption of unhealthy foods and beverages from an early age.
A novel pathogenic splice-site variant in the PTCH1 gene c.3549+1G>T, associated with Gorlin syndrome: a case report
Authors: Conde-Rubio Paula , García-Malinis Ana Julia , Salvador-Rupérez Elvira , Izquierdo Álvarez Silvia , González-Tarancón Ricardo
Published: December 2023

Background

Gorlin syndrome (GS) is a rare genetic disorder inherited in an autosomal dominant manner caused by genetic variants in PTCH1, SUFU, or PTCH2 genes. It is characterized by multiple basal cell carcinomas, odontogenic keratocysts, skeletal abnormalities, and predisposition to neoplasms.

Case presentation

A novel splice-site variant in the PTCH1 gene, c.3549+1G>T classified as pathogenic, was identified in a patient with a phenotype compatible with GS (multiple basal cell carcinomas and skeletal malformations).

Conclusions

This case contributes to expand the spectrum of identified variants in Gorlin syndrome increasing knowledge about molecular bases and the diagnosis approach of this syndrome.
Aortic regurgitation in athletes: the challenges of echocardiographic interpretation
Authors: Chatrath Nikhil , O’Driscoll Jamie , Sharma Sanjay , Papadakis Michael
Published: December 2023

Background

Bicuspid aortic valve (BAV) is the most common congenital cardiac defect and prone to premature degeneration causing aortic regurgitation (AR). The assessment of AR in athletic individuals poses several challenges as the pathological left ventricle (LV) remodelling caused by AR may overlap with the physiological remodelling of intense exercise. The purpose of this study is to highlight these challenges, review the existing literature and discuss how to tackle these conundrums. As a real-world example, we compare the resting transthoracic echocardiographic (TTE) findings in a cohort of individuals with BAV and AR, sub-grouped into “highly active” or “lightly active”.

Methods

Adult male subjects with an index TTE performed at a tertiary referral centre between 2019 and 2022 were included if the TTE confirmed a BAV and at least moderate AR. Further strict inclusion criteria were applied and parameters of valve disease severity was made in accordance with existing guidelines. Subjects completed a physical activity questionnaire over the telephone, and were classified into either group 1: “highly active” or group 2: “lightly active” based on their answers. Demographics and TTE parameters were compared between the two groups.

Results

30 male subjects (mean age 44 ± 13 years) with BAV-AR were included – 17 were highly active, and 13 lightly active. There was no significant difference in age (group 1, 45 ± 12.7 years vs. group 2, 42 ± 17 years; p = 0.49), height (p = 0.45), weight (p = 0.268) or severity of AR, when quantitative assessment was possible. Group 1 had a significantly higher stroke volume (131 ± 17mls vs. 102 ± 13 mls; p = 0.027), larger LV volumes, diastolic dimensions and significantly larger bi-atrial and right ventricular size. This LV dilatation in the context of AR and athleticism poses a diagnostic and management conundrum. Despite this, none of these 17 highly active individuals demonstrated any of the traditional criteria used to consider surgery.

Conclusion

There is significant overlap between the physiological adaptations to exercise and those caused by AR. Multi-modality imaging and stress testing can aid clinicians in diagnostic and management decisions in exercising individuals when there is discordance between AR severity and symptoms.
Management of sleep disorders in autism spectrum disorder with co-occurring attention-deficit hyperactivity disorder: update for clinicians
Authors: Petti Theodore , Gupta Mayank , Fradkin Yuli , Gupta Nihit
Published: December 2023

Aims

To update and examine available literature germane to the recognition, assessment and treatment of comorbid autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD) and sleep disruption, with a predominant focus on children, adolescents and emerging adults.

Background

Considerable overlaps exist among ASD, ADHD and sleep disruption. Literature and guidance for clinicians, administrators, policy makers and families have been limited, as such deliberations were rarely considered until 2013.

Method

This narrative review of the literature addressing sleep disruption issues among those with ASD, ADHD and comorbid ASD and ADHD involved searching multiple databases and use of reverse citations up to the end of September 2022. Emphasis is placed on secondary sources and relevant data for clinical practice.

Results

Complex clinical presentations of ASD/ADHD/sleep disruption are frequently encountered in clinical practice. Prior to 2013, prevalence, clinical presentation, pathophysiology, prognosis, other sleep-related factors and interventions were determined separately for each disorder, often with overlapping objective and subjective methods employed in the process. High percentages of ADHD and ASD patients have both disorders and sleep disruption. Here, the extant literature is integrated to provide a multidimensional understanding of the relevant issues and insights, allowing enhanced awareness and better care of this complex clinical population. Database limitations are considered.

Conclusions

Assessment of ASD symptomatology in youth with ADHD, and the reverse, in cases with disrupted sleep is critical to address the special challenges for case formulation and treatment. Evidence-based approaches to treatment planning and multi-treatment modalities should consider combining psychosocial and biological interventions to address the complexities of each case.
Association of clinical symptoms and cardiometabolic dysregulations in patients with schizophrenia spectrum disorders
Authors: Zhao Chenxu , Habtewold Tesfa Dejenie , Naderi Elnaz , Liemburg Edith J. ,   GROUP Investigators, Bruggeman Richard , Alizadeh Behrooz Z.
Published: December 2023

Background

Patients with schizophrenia spectrum disorders (SSD) have a shortened life expectancy related to cardiovascular diseases. We investigated the association of cognitive, positive, and negative symptoms with cardiometabolic dysregulations in SSD patients.

Methods

Overall, 1,119 patients from the Genetic Risk and Outcome in Psychosis (GROUP) study were included. Cognitive function, positive and negative symptoms were assessed at baseline, 3-year, and 6-year. Cardiometabolic biomarkers were measured at 3-year follow-up. We used linear and multinomial logistic regression models to test the association between cardiometabolic biomarkers and clinical trajectories and performed mediation analyzes, while adjusting for clinical and demographic confounders.

Results

Cognitive performance was inversely associated with increased body mass index (mean difference [β], βhigh = −1.24, 95% CI = –2.28 to 0.20, P = 0.02) and systolic blood pressure (βmild = 2.74, 95% CI = 0.11 to 5.37, P = 0.04). The severity of positive symptoms was associated with increased glycated hemoglobin (HbA1c) levels (βlow = −2.01, 95% CI = −3.21 to −0.82, P = 0.001). Increased diastolic blood pressure (ORhigh-decreased = 1.04, 95% CI = 1.01 to 1.08, P = 0.02; ORhigh-increased = 1.04, 95% CI = 1.00 to 1.08, P = 0.048) and decreased high-density lipoprotein (OR high-increased = 6.25, 95% CI = 1.81 to 21.59, P = 0.004) were associated with more severe negative symptoms. Increased HbA1c (ORmoderate = 1.05, 95% CI = 1.01 to 1.10, P = 0.024; ORhigh = 1.08, 95% CI = 1.02 to 1.14, P = 0.006) was associated with more severe positive symptoms. These associations were not mediated by antipsychotics.

Conclusions

We showed an association between cardiometabolic dysregulations and clinical and cognitive symptoms in SSD patients. The observed associations underscore the need for early identification of patients at risk of cardiometabolic outcomes.
A Plasma Metabolite Score Related to Psychological Distress and Diabetes Risk: A Nested Case-control Study in US Women
Authors: Huang Tianyi , Zhu Yiwen , Shutta Katherine H , Balasubramanian Raji , Zeleznik Oana A , Rexrode Kathryn M , Clish Clary B , Sun Qi , Hu Frank B , Kubzansky Laura D , Hankinson Susan E
Published: December 2023

Context

Psychological distress has been linked to diabetes risk. Few population-based, epidemiologic studies have investigated the potential molecular mechanisms (eg, metabolic dysregulation) underlying this association.

Objective

To evaluate the association between a metabolomic signature for psychological distress and diabetes risk.

Methods

We conducted a nested case-control study of plasma metabolomics and diabetes risk in the Nurses' Health Study, including 728 women (mean age: 55.2 years) with incident diabetes and 728 matched controls. Blood samples were collected between 1989 and 1990 and incident diabetes was diagnosed between 1992 and 2008. Based on our prior work, we calculated a weighted plasma metabolite-based distress score (MDS) comprised of 19 metabolites. We used conditional logistic regression accounting for matching factors and other diabetes risk factors to estimate odds ratios (OR) and 95% confidence intervals (CI) for diabetes risk according to MDS.

Results

After adjusting for sociodemographic factors, family history of diabetes, and health behaviors, the OR (95% CI) for diabetes risk across quintiles of the MDS was 1.00 (reference) for Q1, 1.16 (0.77, 1.73) for Q2, 1.30 (0.88, 1.91) for Q3, 1.99 (1.36, 2.92) for Q4, and 2.47 (1.66, 3.67) for Q5. Each SD increase in MDS was associated with 36% higher diabetes risk (95% CI: 1.21, 1.54; P-trend <.0001). This association was moderately attenuated after additional adjustment for body mass index (comparable OR: 1.17; 95% CI: 1.02, 1.35; P-trend = .02). The MDS explained 17.6% of the association between self-reported psychological distress (defined as presence of depression or anxiety symptoms) and diabetes risk (P = .04).

Conclusion

MDS was significantly associated with diabetes risk in women. These results suggest that differences in multiple lipid and amino acid metabolites may underlie the observed association between psychological distress and diabetes risk.
NGAL Mediates Anaplastic Thyroid Carcinoma Cells Survival Through FAS/CD95 Inhibition
Authors: Crescenzi Elvira , Mellone Stefano , Gragnano Gianluca , Iaccarino Antonino , Leonardi Antonio , Pacifico Francesco
Published: December 2023

Neutrophil gelatinase-associated lipocalin (NGAL), a siderophore-mediated iron binding protein, is highly expressed in human anaplastic thyroid carcinomas (ATCs) where it plays pleiotropic protumorigenic roles including that of a prosurvival protein. Here we show that NGAL inhibits FAS/CD95 death receptor to control ATC cell survival. FAS/CD95 expression in human specimens from patients with ATC and in ATC-derived cell lines negatively correlate with NGAL expression. Silencing of NGAL in ATC cells leads to FAS/CD95 upregulation, whereas NGAL overexpression determines the opposite effect. As a result, an agonist anti-FAS/CD95 antibody induces cell death in NGAL-silenced cells while it is ineffective on NGAL-overexpressing cells. Interestingly, the inhibitory activity of NGAL on FAS/CD95 is due to its iron carrier property given that perturbing iron homeostasis of NGAL-proficient and -deficient ATC cells directly influences FAS/CD95 expression. Accordingly, conditioned media containing a mutant form of NGAL unable to bind siderophores cannot rescue cells from FAS/CD95-dependent death, whereas NGAL wild type–containing conditioned media abolish the effects of the agonist antibody. We also find that downregulation of FAS/CD95 expression is mediated by iron-dependent NGAL suppression of p53 transcriptional activity. Our results indicate that NGAL contributes to ATC cell survival by iron-mediated inhibition of p53-dependent FAS/CD95 expression and suggest that restoring FAS/CD95 by NGAL suppression could be a helpful strategy to kill ATC cells.
Differential Effects of PTH (1-34), PTHrP (1-36), and Abaloparatide on the Murine Osteoblast Transcriptome
Authors: Mosca Michael J , He Zhiming , Ricarte Florante R , Le Henaff Carole , Partridge Nicola C
Published: December 2023

Teriparatide (PTH (1-34)), PTHrP (1-36), and abaloparatide (ABL) have been used for the treatment of osteoporosis, but their efficacy long term is significantly limited. The 3 peptides exert time- and dose-dependent differential responses in osteoblasts, leading us to hypothesize they may also differentially modulate the osteoblast transcriptome. Treatment of mouse calvarial osteoblasts with 1 nM of the peptides for 4 hours results in RNA sequencing data with PTH (1-34) regulating 367 genes, including 194 unique genes; PTHrP (1-36) regulating 117 genes, including 15 unique genes; and ABL regulating 179 genes, including 20 unique genes. There were 83 genes shared among all 3 peptides. Gene ontology analyses showed similarities in Wnt signaling, cAMP-mediated signaling, ossification, but differences in morphogenesis of a branching structure in biological processes; receptor ligand activity, transcription factor activity, and cytokine receptor/binding activity in molecular functions. The peptides increased Vdr, Cited1, and Pde10a messenger RNAs (mRNAs) in a pattern similar to Rankl, that is, PTH (1-34) greater than ABL greater than PTHrP (1-36). mRNA abundance of other genes, including Wnt4, Wnt7, Wnt11, Sfrp4, Dkk1, Kcnk10, Hdac4, Epn3, Tcf7, Crem, Fzd5, Ppp2r2a, and Dvl3, showed that some genes were regulated similarly by all 3 peptides; others were not. Finally, small interfering RNA knockdowns of SIK1/2/3 and CRTC1/2/3 in PTH (1-34)–treated cells revealed that Vdr and Wnt4 genes are regulated by salt-inducible kinases (SIKs) and CREB-regulated transcriptional coactivators (CRTCs), while others are not. Although many studies have examined PTH signaling in the osteoblast/osteocyte, ours is the first to compare the global effects of these peptides on the osteoblast transcriptome or to analyze the roles of the SIKs and CRTCs.
Bibliometric Analysis of Contributions of Anesthesiology Journals and Anesthesiologists to Operating Room Management Science
Authors: Dexter Franklin , Scheib Sara , Xie Wei , Epstein Richard H.
Published: December 2023

BACKGROUND:

Anesthesiology journals appear to have been progressively publishing a smaller percentage of operating room (OR) management studies. Similarly, non-anesthesiologists have increasingly been authors of these publications. Five hypotheses were formulated to evaluate these impressions based on 2 of the authors’ curation of an online, comprehensive bibliography of OR management articles and corresponding referenced course materials.

METHODS:

We studied all 2938 publications having Scopus’ SciVal topic T.6319 (OR management) more than 28 years from 1996 through May 2023, including 8608 distinct authors.

RESULTS:

Half (50%) of the publications were absent from PubMed, and the percentage absent has been increasing progressively (Kendall’s τ = 0.71; P < .0001). Fewer than half were published in journals including anesthesiology as the sole classification (20%) or as one of the classifications (27%). The anesthesiology journals have been publishing a progressively decreasing fraction (τ = −0.61; P < .0001). Among the 11 authors each contributing at least 1% of the OR management science publications, 9 were anesthesiologists and the other 2 had anesthesiologists as coauthors on all these publications. Only 3% of authors had at least 10 OR management publications from earlier years. There were 75% of authors with no such earlier publications and 85% with 0 or 1. There was a progressive increase in the number of authors publishing OR management annually and with at most 1 such earlier publication (τ = 0.90; P < .0001). Only 20% of publications had any author with at least 10 earlier OR management publications, 48% had every author with no such earlier publications, and 60% had all authors with 0 or 1.

CONCLUSIONS:

Although most of the authors with the greatest production of OR management science were anesthesiologists, the percentage of publications in anesthesiology journals has been decreasing progressively. Anesthesiologists cannot rely solely on anesthesiology journals to keep up with the field. For most publications, every author had few or no earlier publications on the topic. Clinicians and managers relying on OR management science will continue to need to apply more information when judging whether published results can reliably be applied to their facilities.
Repeat, Bilateral Femoral Nerve Blocks With Liposomal Bupivacaine for Analgesia in a Patient With Calciphylaxis: A Case Report
Authors: Catalano Taylor D. , Orza Daniela , Orza Florin M.
Published: December 2023

A 39-year-old woman with juvenile idiopathic arthritis complicated by nonuremic calciphylaxis presented for pain management of bilateral lower extremity wounds requiring frequent dressing changes. Bilateral single-shot femoral nerve blocks using liposomal bupivacaine and 0.25% bupivacaine were performed. The patient reported decreased pain scores and had reduced opioid use for 72 hours postblock. Repeat, bilateral single-shot femoral nerve blocks with liposomal bupivacaine and 0.25% bupivacaine were performed approximately every 72 hours to maintain adequate analgesia. We conclude that off-label use of liposomal bupivacaine in femoral nerve blocks results in prolonged block duration without adverse effects or tachyphylaxis.
A Case Report of Tension Hydrothorax Incited by Bowel Perforation
Authors: Sanchez Kyle J. , Walsh Elisa C. , Bittner Edward A. , Ruscic Katarina J.
Published: December 2023

We report the case of a 34-year-old man who developed cardiac arrest due to tension hydrothorax from colonic perforation. Tension hydrothorax, an entity characterized by pleural effusion leading to mediastinal compression, has not been reported in association with intraabdominal inflammation. Our patient developed respiratory insufficiency after repair of colonic perforation, followed by respiratory failure and cardiac arrest. Transthoracic echocardiography provided rapid diagnosis during decompensation and prompted a lifesaving thoracostomy. Clinicians should consider tension hydrothorax as a rare cause of hemodynamic collapse, even in the absence of liver failure, and use bedside tools like transthoracic echocardiography to facilitate diagnosis and intervention.
Deathlife
Authors: Pinn Anthony B.
Published: December 2023

In Deathlife, Anthony B. Pinn analyzes hip hop to explore how Blackness serves as a framework for defining and guiding the relationship between life and death in the United States. Pinn argues that white supremacy and white privilege operate based on the right to distinguish death from life. This distinction is produced and maintained through the construction of Blackness as deathlife. Drawing on Afropessimism and Black moralism, Pinn theorizes deathlife as a technology of whiteness that projects whites' anxieties about the end of their lives onto the Black other. Examining the music of Jay-Z; Kendrick Lamar; Tyler, the Creator; and others, Pinn shows how hip hop configures the interconnection and dependence between death and life in such a way that death and life become indistinguishable. In so doing, Pinn demonstrates that hip hop presents an alternative to deathlife that challenges the white supremacist definitions of Blackness and anti-Blackness more generally.