bluuebunny/crossref_metadata_2025 huggingface dataset:
VirBot: an RNA viral contig detector for metagenomic data
Authors: Chen Guowei , Tang Xubo , Shi Mang , Sun Yanni
Published: February 2023

Without relying on cultivation, metagenomic sequencing greatly accelerated the novel RNA virus detection. However, it is not trivial to accurately identify RNA viral contigs from a mixture of species. The low content of RNA viruses in metagenomic data requires a highly specific detector, while new RNA viruses can exhibit high genetic diversity, posing a challenge for alignment-based tools. In this work, we developed VirBot, a simple yet effective RNA virus identification tool based on the protein families and the corresponding adaptive score cutoffs. We benchmarked it with seven popular tools for virus identification on both simulated and real sequencing data. VirBot shows its high specificity in metagenomic datasets and superior sensitivity in detecting novel RNA viruses.

Availability and implementation

https://github.com/GreyGuoweiChen/RNA_virus_detector

Supplementary information

Supplementary data are available at Bioinformatics online.
Why is there an “oversupply” of human ovarian follicles?
Authors: Lawley Sean D , Johnson Joshua
Published: February 2023

Women are born with hundreds of thousands to over a million primordial ovarian follicles (PFs) in their ovarian reserve. However, only a few hundred PFs will ever ovulate and produce a mature egg. Why are hundreds of thousands of PFs endowed around the time of birth when far fewer follicles are required for ongoing ovarian endocrine function and only a few hundred will survive to ovulate? Recent experimental, bioinformatics, and mathematical analyses support the hypothesis that PF growth activation (PFGA) is inherently stochastic. In this paper, we propose that the oversupply of PFs at birth enables a simple stochastic PFGA mechanism to yield a steady supply of growing follicles that lasts for several decades. Assuming stochastic PFGA, we apply extreme value theory to histological PF count data to show that the supply of growing follicles is remarkably robust to a variety of perturbations and that the timing of ovarian function cessation (age of natural menopause) is surprisingly tightly controlled. Though stochasticity is often viewed as an obstacle in physiology and PF oversupply has been called “wasteful,” this analysis suggests that stochastic PFGA and PF oversupply function together to ensure robust and reliable female reproductive aging.
A petunia transcription factor, PhOBF1, regulates flower senescence by modulating gibberellin biosynthesis
Authors: Ji Xiaotong , Xin Ziwei , Yuan Yanping , Wang Meiling , Lu Xinyi , Li Jiaqi , Zhang Yanlong , Niu Lixin , Jiang Cai-Zhong , Sun Daoyang
Published: February 2023

Flower senescence is commonly enhanced by the endogenous hormone ethylene and suppressed by the gibberellins (GAs) in plants. However, the detailed mechanisms for the antagonism of these hormones during flower senescence remain elusive. In this study, we characterized one up-regulated gene PhOBF1, belonging to the basic leucine zipper transcription factor family, in senescing petals of petunia (Petunia hybrida). Exogenous treatments with ethylene and GA3 provoked a dramatic increase in PhOBF1 transcripts. Compared with wild-type plants, PhOBF1-RNAi transgenic petunia plants exhibited shortened flower longevity, while overexpression of PhOBF1 resulted in delayed flower senescence. Transcript abundances of two senescence-related genes PhSAG12 and PhSAG29 were higher in PhOBF1-silenced plants but lower in PhOBF1-overexpressing plants. Silencing and overexpression of PhOBF1 affected expression levels of a few genes involved in the GA biosynthesis and signaling pathways, as well as accumulation levels of bioactive GAs GA1 and GA3. Application of GA3 restored the accelerated petal senescence to normal levels in PhOBF1-RNAi transgenic petunia lines, and reduced ethylene release and transcription of three ethylene biosynthetic genes PhACO1, PhACS1, and PhACS2. Moreover, PhOBF1 was observed to specifically bind to the PhGA20ox3 promoter containing a G-box motif. Transient silencing of PhGA20ox3 in petunia plants through tobacco rattle virus-based virus-induced gene silencing method led to accelerated corolla senescence. Our results suggest that PhOBF1 functions as a negative regulator of ethylene-mediated flower senescence by modulating the GA production.
Uniportal video-assisted thoracoscopic surgery esophagectomy outcomes in 40 consecutive patients
Authors: Aslan Sezer , Tiryaki Gamze Gul , Pashayev Jeyhun , Cetinkaya Cagatay , Durusoy Ali Fuad , Ermerak Nezih Onur , Batirel Hasan Fevzi
Published: February 2023

OBJECTIVES

Minimally invasive esophagectomy has improved over time becoming faster and less invasive. We have changed our technical approach from multiportal to uniportal video-assisted thoracoscopic surgery (VATS) esophagectomy over the years. In this study, we analysed our results with uniportal VATS esophagectomy technique.

METHODS

This study was a retrospective analysis of 40 consecutive patients with the intent to perform uniportal VATS esophagectomy for esophageal cancer between July 2017 and August 2021. Demographic criteria, comorbidities, neoadjuvant therapy, intraoperative data, complications, length of stay, pathological data, 30- and 90-day mortality and 2-year survival data were recorded.

RESULTS

Forty patients (21 female) were operated (median age 62.9 [53.5–70.25]). Eighteen patients (45%) received neoadjuvant chemoradiation. The chest part of all cases was started with uniportal VATS and 31 (77.5%) was completed uniportally (34 Ivor Lewis, 6 McKeown). The median thoracic operation time in minimally invasive Ivor Lewis esophagectomy was 90 min (77.5–100). The median time for uniportal side-to-side anastomosis was 12 min (11–16). Five (12.5%) patients had leak, and 4 were intrathoracic. Twenty-eight (70%) patients had squamous cell carcinoma, 11 adenocarcinoma and 1 squamous cell carcinoma with sarcomatoid differentiation. Thirty-seven (92.5%) patients had R0 resection. The mean number of lymph nodes dissected was 24 ± 9.5. Thirty- and ninety-day mortality was 2.5% (n = 1). The mean follow-up was 44 ± 2.8 months. Two-year survival was 80%.

CONCLUSIONS

Uniportal VATS esophagectomy is a safe, fast and feasible alternative to other minimally invasive and open approaches. Comparable results to contemporary series are observed in perioperative and oncologic outcomes.
Climbing robots for manufacturing
Authors: Tao Bo , Gong Zeyu , Ding Han
Published: February 2023

Robotized intelligent manufacturing is a growing trend in the manufacturing of large and complex components in aviation, aerospace, marine engineering and other industries. With their expansive workspaces and flexible deployment, climbing manufacturing robots can create a revolutionary manufacturing paradigm for large and complex components. This paper defines the climbing manufacturing robot based on the application status of climbing robots and then analyzes four key technical requirements: adhesion, locomotion, localization and control. Subsequently, the current research status of climbing robots in these four areas is classified and reviewed, along with a clarification of the research frontiers and trends in each area, and the applicability of the relevant research to manufacturing-oriented climbing robotic systems is analyzed. Finally, by concluding the development trends of robotized intelligent manufacturing equipment in terms of manufacturing dimension and scale, environmental adaptability and cluster collaboration capability, we clarify the major challenges for climbing manufacturing robots in terms of adhesion principles, motion mechanisms, positioning technology and control methods, and propose future research directions in these fields.
Does changing perceptions of sleep by incorporating sleep wearables improve insomnia? Protocol for a randomized study (the Novel Insomnia Treatment Experiment)
Authors: Spina Marie-Antoinette , Andrillon Thomas , Wiley Joshua F , Rajaratnam Shantha M W , Bei Bei
Published: February 2023

Study Objectives

Insomnia is common in the general population and is diagnosed based on self-reported sleep complaints. There is a frequent discrepancy between objectively recorded and self-reported sleep (sleep–wake state discrepancy), especially in individuals with insomnia. Although sleep–wake state discrepancy is well-documented in the literature, it is not well understood. This protocol describes the methodology of a randomized control study, which will examine whether providing monitoring and feedback about objectively recorded sleep with support for interpretation of sleep–wake state discrepancy improves insomnia symptoms and will explore the potential mechanisms of change.

Methods

Participants are 90 individuals with insomnia symptoms (Insomnia Severity Index [ISI] ≥10). Participants will be randomized to one of two conditions: (1) Intervention: feedback about objectively recorded sleep (actigraph and optional electroencephalogram headband) with guidance for data interpretation, (2) Control: sleep hygiene session. Both conditions will involve individual sessions and two check-in calls. The primary outcome is ISI score. Secondary outcomes include sleep-related impairment, symptoms of anxiety and depression, and other sleep and quality of life measures. Outcomes will be assessed using validated instruments at baseline and post-intervention.

Discussion

With increasing number of wearable devices that measure sleep, there is a need to understand how sleep data provided by these devices could be utilized in the treatment of insomnia. Findings from this study have the potential to better understand sleep–wake state discrepancy in insomnia and uncover new approaches to supplement current insomnia treatment.
“Am I the Only One Who Feels Like This?”: Needs Expressed Online by Abortion Seekers
Authors: Lands Madison , Carpenter Emma , Valley Taryn , Jacques Laura , Higgins Jenny
Published: February 2023

In the United States, abortion is safe and common, but highly stigmatized and frequently targeted by legislation that aims to restrict access. Numerous obstacles impede access to abortion care, including logistical barriers like cost and transportation, limited clinic availability, and state-mandated waiting periods. Accurate abortion information can also be hard to access. To overcome these barriers, many people seeking abortion turn to anonymous online forums, including Reddit, for information and support. Examining this community provides a unique perspective on the questions, thoughts, and needs of people considering or undergoing an abortion. The authors web scraped 250 posts from subreddits that contain abortion-related posts, then coded deidentified posts using a combined deductive/inductive approach. The authors identified a subset of these codes in which users were giving/seeking information and advice on Reddit, then engaged in a targeted analysis of the needs expressed in these posts. Three interconnected needs emerged: (1) need for information, (2) need for emotional support, and (3) need for community around the abortion experience. In this study map the authors reflected these needs onto key social work practice areas and competencies; taken alongside support from social work’s governing bodies, this research suggests that social workers would be beneficial additions to the abortion care workforce.
CCN6 influences transcription and controls mitochondrial mass and muscle organization
Authors: Ganguly Ananya , Padhan Deepesh Kumar , Sengupta Archya , Chakraborty Pritam , Sen Malini
Published: February 2023

Mutations in Cellular Communication Network Factor 6 (CCN6) are linked to the debilitating musculoskeletal disease Progressive Pseudo Rheumatoid Dysplasia (PPRD), which disrupts mobility. Yet, much remains unknown about CCN6 function at the molecular level. In this study, we revealed a new function of CCN6 in transcriptional regulation. We demonstrated that CCN6 localizes to chromatin and associates with RNA Polymerase II in human chondrocyte lines. Using zebrafish as a model organism we validated the nuclear presence of CCN6 and its association with RNA Polymerase II in different developmental stages from 10 hpf embryo to adult fish muscle. In concurrence with these findings, we confirmed the requirement of CCN6 in the transcription of several genes encoding mitochondrial electron transport complex proteins in the zebrafish, both in the embryonic stages and in the adult muscle. Reduction in the expression of these genes upon morpholino‐mediated knockdown of CCN6 protein expression led to reduced mitochondrial mass, which correlated with defective myotome organization during zebrafish muscle development. Overall, this study suggests that the developmental musculoskeletal abnormalities linked with PPRD could be contributed at least partly by impaired expression of genes encoding mitochondrial electron transport complexes due to defects in CCN6 associated transcriptional regulation.
Discrimination 911: A Novel Response Framework to Teach Bystanders to Become Upstanders When Facing Microaggressions
Authors: Rubenstein Jared , Rahiem Sahar , Nelapati Shimei S. , Arevalo Soriano Tatiana , Tatem Andria
Published: February 2023

Problem

Microaggressions are pervasive in daily life, including in undergraduate and graduate medical education and across health care settings. The authors created a response framework (i.e., a series of algorithms) to help bystanders (i.e., health care team members) become upstanders when witnessing discrimination by the patient or patient’s family toward colleagues at the bedside during patient care, Texas Children’s Hospital, August 2020 to December 2021.

Approach

Similar to a medical “code blue,” microaggressions in the context of patient care are foreseeable yet unpredictable, emotionally jarring, and often high-stakes. Modeled after algorithms for medical resuscitations, the authors used existing literature to create a series of algorithms, called Discrimination 911, to teach individuals how to intervene as an upstander when witnessing instances of discrimination. The algorithms “diagnose” the discriminatory act, provide a process to respond with scripted language, and subsequently support a colleague who was targeted. The algorithms are accompanied by training on communication skills and diversity, equity, and inclusion principles via a 3-hour workshop that includes didactics and iterative role play. The algorithms were designed in the summer of 2020 and refined through pilot workshops throughout 2021.

Outcomes

As of August 2022, 5 workshops have been conducted with 91 participants who also completed the post-workshop survey. Eighty (88%) participants reported witnessing discrimination from a patient or patient’s family toward a health care professional, and 89 (98%) participants stated that they would use this training to make changes in their practice.

Next Steps

The next phase of the project will involve continued dissemination of the workshop and algorithms as well as developing a plan to obtain follow-up data in an incremental fashion to assess for behavior change. To reach this goal, the authors have considered changing the format of the training and are planning to train additional facilitators.
Treatment of patients with ‘do not intubate orders’
Authors: Cammarota Gianmaria , Simonte Rachele , De Robertis Edoardo
Published: February 2023

Purpose of review

Do-not-intubate (DNI) orders are more frequently encountered over time. This widespread diffusion of DNI orders make it essential to develop therapeutic strategies matching patient's and his family willingness. The present review sheds light on the therapeutic approaches employed to support respiratory function of patients with DNI orders.

Recent findings

In DNI patients, several approaches have been described to relieve dyspnoea and address acute respiratory failure (ARF). Despite its extensive use, supplemental oxygen is not so useful in assuring dyspnoea relief. Noninvasive respiratory support (NIRS) is frequently employed to treat ARF in DNI patients. Also, to enhance DNI patients comfort during NIRS, it is worthy to point out the role of analgo-sedative medications. Lastly, a particular aspect concerns the first waves of coronavirus disease 2019 pandemic, when DNI orders have been pursued on factors unrelated to patient's wishes, in the total absence of family support due to the lockdown policy. In this setting, NIRS has been extensively employed in DNI patients with a survival rate of around 20%.

In dealing with DNI patients, the individualization of treatments is of pivotal importance to respect patient's preferences and improve quality of life at the same time.
Current concepts in preoperative anemia management in obstetrics
Authors: Wiesenack Christoph , Meybohm Patrick , Neef Vanessa , Kranke Peter
Published: February 2023

Purpose of review

The purpose of this article is to provide an overview of currently recommended treatment approaches for anemia during pregnancy, with a special focus on iron deficiency and iron deficiency anemia (IDA).

Recent findings

As consistent patient blood management (PBM) guidelines in obstetrics are still lacking, recommendations regarding the timing of anemia screening and the treatment recommendations for iron deficiency and IDA during pregnancy are still controversial so far. Based on increasing evidence, early screening for anemia and iron deficiency should be recommended at the beginning of each pregnancy. To reduce maternal and fetal burden, any iron deficiency, even without anemia, should be treated as early as possible during pregnancy. While oral iron supplements administered every other day are the standard treatment in the first trimester, the use of intravenous iron supplements is increasingly suggested from the second trimester onwards.

The treatment of anemia, and more specifically iron deficiency anemia during pregnancy, holds many possibilities for improvement. The fact that the period of risk is known well in advance and thus there is a long optimization phase is per se an ideal prerequisite for the best possible therapy of treatable causes of anemia. Standardization of recommendations and guidelines for screening and treatment of IDA in obstetrics is required for the future. In any case, a multidisciplinary consent is the precondition for a successfully implementation of anemia management in obstetrics to establish an approved algorithm easily enabling detection and treatment of IDA during pregnancy.
Safety and quality in paediatric procedural sedation: what really matters?
Authors: Röher Katharina , Becke-Jakob Karin , Eich Christoph
Published: February 2023

Purpose of review

This review gives an overview of the safety aspects for paediatric procedural sedation and a discussion of possibilities for optimizing structure, processes and outcomes.

Recent findings

Procedural sedation in paediatric patients is performed by providers of different specialties and compliance with safety standards is a basic requirement regardless of provider specialty. This includes preprocedural evaluation, monitoring, equipment and profound expertise of sedation teams. The choice of sedative medications and the possibility of incorporating nonpharmacological methods play an important role for optimal outcome. In addition, an ideal outcome from the patient's perspective includes optimized processes and clear and empathetic communication.

Institutions providing paediatric procedural sedation must ensure the comprehensive training of sedations teams. Furthermore, institutional standards for equipment, processes and optimal choice of medication depending on performed procedure and comorbidities of the patient must be established. At the same time, organizational and communication aspects should be considered.
Universal Repeat Screening for Human Immunodeficiency Virus in the Third Trimester of Pregnancy
Authors: Hawkinson Lila F. , Chaiken Sarina R. , Doshi Uma , Wallace Jessica , Caughey Aaron B.
Published: February 2023

OBJECTIVE:

To assess the cost effectiveness of universal repeat screening for human immunodeficiency virus (HIV) infection in the third trimester of pregnancy.

METHODS:

A decision-analytic model was constructed to compare two strategies: screening for HIV infection in the first trimester alone compared with the addition of repeat screening in the third trimester. Probabilities, costs, and utilities were derived from the literature and varied in sensitivity analyses. The assumed incidence of HIV infection in pregnancy was 0.0145% or 14.5 per 100,000. Outcomes included costs (in 2022 U.S. dollars), maternal and neonatal quality-adjusted life-years (QALYs), and cases of neonatal HIV infection. Our theoretical cohort contained 3.8 million pregnant individuals, the approximate number of births per year in the United States. The willingness-to-pay threshold was set at $100,000/QALY. We performed univariable and multivariable sensitivity analyses to determine inputs that most influenced the model.

RESULTS:

Universal third-trimester screening prevented 133 cases of neonatal HIV infection in this theoretical cohort. Universal third-trimester screening led to an increased cost of $17.54 million and 2,732 increased QALYs, with an incremental cost-effectiveness ratio of $6,418.56 per QALY, less than the willingness-to-pay threshold. In a univariate sensitivity analysis, third-trimester screening remained cost effective with variation of HIV incidence in pregnancy to as low as 0.0052%.

CONCLUSION:

In a theoretical U.S.-based cohort of pregnant individuals, universal repeat screening for HIV infection in the third trimester was found to be cost effective and to reduce vertical transmission of HIV. These results merit consideration of a broader HIV-screening program in the third trimester.
Neuromonitoring in Critically Ill Patients
Authors: Rajagopalan Swarna , Sarwal Aarti
Published: February 2023

OBJECTIVES:

Critically ill patients are at high risk of acute brain injury. Bedside multimodality neuromonitoring techniques can provide a direct assessment of physiologic interactions between systemic derangements and intracranial processes and offer the potential for early detection of neurologic deterioration before clinically manifest signs occur. Neuromonitoring provides measurable parameters of new or evolving brain injury that can be used as a target for investigating various therapeutic interventions, monitoring treatment responses, and testing clinical paradigms that could reduce secondary brain injury and improve clinical outcomes. Further investigations may also reveal neuromonitoring markers that can assist in neuroprognostication. We provide an up-to-date summary of clinical applications, risks, benefits, and challenges of various invasive and noninvasive neuromonitoring modalities.

DATA SOURCES:

English articles were retrieved using pertinent search terms related to invasive and noninvasive neuromonitoring techniques in PubMed and CINAHL.

STUDY SELECTION:

Original research, review articles, commentaries, and guidelines.

DATA EXTRACTION:

Syntheses of data retrieved from relevant publications are summarized into a narrative review.

DATA SYNTHESIS:

A cascade of cerebral and systemic pathophysiological processes can compound neuronal damage in critically ill patients. Numerous neuromonitoring modalities and their clinical applications have been investigated in critically ill patients that monitor a range of neurologic physiologic processes, including clinical neurologic assessments, electrophysiology tests, cerebral blood flow, substrate delivery, substrate utilization, and cellular metabolism. Most studies in neuromonitoring have focused on traumatic brain injury, with a paucity of data on other clinical types of acute brain injury. We provide a concise summary of the most commonly used invasive and noninvasive neuromonitoring techniques, their associated risks, their bedside clinical application, and the implications of common findings to guide evaluation and management of critically ill patients.

CONCLUSIONS:

Neuromonitoring techniques provide an essential tool to facilitate early detection and treatment of acute brain injury in critical care. Awareness of the nuances of their use and clinical applications can empower the intensive care team with tools to potentially reduce the burden of neurologic morbidity in critically ill patients.
Racial Inequities in Sepsis Mortality Among Children in the United States
Authors: Moorthy Ganga S. , Young Rebecca R. , Smith Michael J. , White Michelle J. , Hong Hwanhee , Kelly Matthew S.
Published: February 2023

Background:

Racial inequities influence health outcomes in the United States, but their impact on sepsis outcomes among children is understudied. We aimed to evaluate for racial inequities in sepsis mortality using a nationally representative sample of pediatric hospitalizations.

Methods:

This population-based, retrospective cohort study used the 2006, 2009, 2012 and 2016 Kids’ Inpatient Database. Eligible children 1 month to 17 years old were identified using sepsis-related International Classification of Diseases, Ninth Revision or International Classification of Diseases, Tenth Revision codes. We used modified Poisson regression to evaluate the association between patient race and in-hospital mortality, clustering by hospital and adjusting for age, sex and year. We used Wald tests to assess for modification of associations between race and mortality by sociodemographic factors, geographic region and insurance status.

Results:

Among 38,234 children with sepsis, 2555 (6.7%) died in-hospital. Compared with White children, mortality was higher among Hispanic (adjusted relative risk: 1.09; 95% confidence interval: 1.05–1.14), Asian/Pacific Islander (1.17, 1.08–1.27) and children from other racial minority groups (1.27, 1.19–1.35). Black children had similar mortality to White children overall (1.02, 0.96–1.07), but higher mortality in the South (7.3% vs. 6.4%; P < 0.0001). Hispanic children had higher mortality than White children in the Midwest (6.9% vs. 5.4%; P < 0.0001), while Asian/Pacific Islander children had higher mortality than all other racial categories in the Midwest (12.6%) and South (12.0%). Mortality was higher among uninsured children than among privately insured children (1.24, 1.17–1.31).

Conclusions:

Risk of in-hospital mortality among children with sepsis in the United States differs by patient race, geographic region and insurance status.
Chronic Disseminated Candidiasis in Children and the Role of Corticosteroids Therapy
Authors: Al Yazidi Laila S. , Elsidig Nagi , Wali Yasser , Nazir Hanan
Published: February 2023

Background:

Little is known about chronic disseminated candidiasis (CDC) in children. This study was done to describe the epidemiology, risk factors and outcome of CDC in children managed at Sultan Qaboos University Hospital (SQUH), Oman, and to describe the role of corticosteroids in the management of immune reconstitution inflammatory syndrome (IRIS) complicating CDC.

Methods:

We retrospectively reported demographic, clinical and laboratory data of all children managed in our center for CDC between January 2013 and December 2021. In addition, we discuss the available literature on the role of corticosteroids for management of CDC-related IRIS in children since 2005.

Results:

Between January 2013 and December 2021, 36 immunocompromised children were diagnosed with invasive fungal infection at our center, of whom 6 had CDC (all with acute leukemia). Their median age was 5.75 years. Prolonged fever despite broad-spectrum antibiotics (6/6) followed by skin rash (4/6) were the most common clinical features of CDC. Four children grew Candida tropicalis from blood or skin. CDC-related IRIS was documented in 5 children (83%) and 2 received corticosteroids. Our literature review revealed that 28 children were managed with corticosteroids for CDC-related IRIS since 2005. The majority of these children had defervescence of fever within 48 hours. Prednisolone of 1–2 mg/kg/day for 2–6 weeks was the most common regimen used. No major side effects reported in these patients.

Conclusion:

CDC is more common in children with acute leukemia and CDC-related IRIS is not uncommon. Corticosteroid therapy looks effective and safe as adjunctive therapy for CDC-related IRIS.
Antidepressant Poisoning Trends in Pediatric Intensive Care
Authors: Gurbanov Anar , Kandemir Hande , Gurbanova Lala , Gün Emrah , Botan Edin , Balaban Burak , Kahveci Fevzi , Özen Hasan , Uçmak Hacer , Özdemir İhsan , Havan Merve , Tekin Deniz , Kendirli Tanil
Published: February 2023

Purpose/Background

This study aimed to compare the frequency, clinical findings, treatment practices, and outcomes of toxicity to old-generation (OG) and new-generation (NG) antidepressants in our pediatric intensive care unit (PICU) by year-to-year.

Methods/Procedures

The study included patients hospitalized for antidepressant poisoning during the 11-year period of January 2010 through December 2020. Antidepressants were classified as OG and NG. The groups were compared in terms of patient demographic characteristics, type of poisoning (accidental/suicidal), clinical findings, supportive and extracorporeal treatments received, and outcomes.

Findings/Results

The study included 58 patients (NG, n = 30; OG, n = 28). The median age of the patients was 178 months (range, 13.6–215 months) and 47 patients (81%) were female. Patients admitted for only antidepressant poisoning constituted 13.3% of all poisoning cases (58/436). Of these, 22 cases (37.9%) were accidental and 36 (62.3%) were suicidal. The most common cause of poisoning was amitriptyline (24/28) in the OG group and sertraline (13/30) in the NG group. Neurological symptoms were significantly more common in the OG group (76.2% vs 23.8%), while gastrointestinal involvement was more common in the NG group (82% vs 18%; P = 0.001 and P = 0.026, respectively). Old-generation antidepressant poisoning was associated with more frequent intubation (4 vs 0 patients, P = 0.048) and longer length of PICU stay (median, 1 day [range, 1–8] vs 1 day [range, 1–4], P = 0.019). Rates of therapeutic plasma exchange and intravenous lipid emulsion therapy did not differ (P = 0.483 and P = 0.229, respectively).

Implications/Conclusions

In poisoned patients, proper evaluation and management of patients requiring PICU admission are vital for favorable patient outcomes.
Peripheral Artery Bypass Graft for the Treatment of Ischemic Ulcer or Severe Pain of Hand in Connective Tissue Diseases
Authors: Kim Jong-Ho , Kim Yumin , Eun Seokchan
Published: February 2023

Chronic ischemia of the hands and feet is a rare medical condition that requires surgical revascularization. In particular, digital ischemia resulting from connective tissue diseases (CTDs) is among the most important manifestations that negatively affect patients' quality of life. Here, we describe a bypass graft technique for treating digital ischemia. This study aimed to share the considerable benefits of surgical intervention for CTD and present a treatment algorithm. From 2009 to 2020, bypass graft surgery was performed on 10 patients with CTD to relieve their ischemic symptoms or ulceration. Preoperative angiography was performed, and blood distribution patterns were analyzed in detail. Based on the angiographic 4-level analysis, bypass graft surgeries were performed accordingly. The postoperative follow-up was 15 to 72 months. Pain in the hands that underwent the bypass graft surgery improved immediately after surgery. All ulcerations healed and the mean time recorded for ulceration healing was 45.7 days. Here, we propose an appropriate surgical treatment algorithm for managing CTD using arterial bypass graft surgery, and its positive long-term results demonstrate that it is an appropriate option for treating digital ischemia. In conclusion, strict measures with precise preoperative planning can provide satisfactory long-term results in patients with CTD.
Reverse Abdominoplasty for Mastectomy Defect Closure in Advanced Breast Cancer
Authors: Whalen Kristen , Liu Langfeier , Rejano Courtney Johns , Mhaskar Rahul , Khakpour Nazanin , Dayicioglu Deniz
Published: February 2023

Background

Breast cancer patients with locally advanced breast cancer who require radical mastectomy are left with large chest wall defects. This poses a significant reconstructive challenge as many high-risk patients require timely postmastectomy adjuvant therapy. While the reverse abdominoplasty technique is commonly used for aesthetic improvement of the anterior trunk, it can be also be effectively used for closure of extensive mastectomy defects in this patient population.

Methods

We conducted a retrospective cohort study of all consecutive patients who underwent an extensive radical mastectomy followed by immediate closure with the reverse abdominoplasty technique at a single tertiary cancer center from June 2017 to July 2022. Patients who had concurrent skin grafting or breast mound flap reconstruction were excluded. Demographic, medical, oncologic, and reconstructive data were collected.

Results

Six patients were treated with reverse abdominoplasty for 9 chest wall defects after surgical excision of locally advanced breast cancer. The median tumor size was 10.7 cm (range, 6.7–10 cm) and the median mastectomy weight was 865.7 g (range, 356.4–1247.7 g). On average, the operation length was 191 minutes (range, 86–257 minutes) and the postoperative length of stay was 2.2 days (range, 1–5 days). All patients underwent systemic adjuvant therapy and the median time from surgery to initiation of therapy was 44.5 days (range, 32–75 days).

Conclusions

Reverse abdominoplasty is a simple and safe technique to reliably close large defects after locally advanced breast cancer excision. It has a short operative time, hospital stay, and turnaround time to initiation of adjuvant therapy.
Ensemble learning for higher diagnostic precision in schizophrenia using peripheral blood gene expression profile
Authors: Wagh Vipul Vilas , Agrawal Suchita , Purohit Shruti , Pachpor Tejaswini , Narlikar Leelavati , Paralikar Vasudeo , Khare Satyajeet
Published: February 2023

The need for molecular biomarkers for schizophrenia has been well recognized. Peripheral blood gene expression profiling and machine learning (ML) tools have recently become popular for biomarker discovery. The stigmatization associated with schizophrenia advocates the need for diagnostic models with higher precision. In this study, we propose a strategy to develop higher-precision ML models using ensemble learning. We performed a meta-analysis using peripheral blood expression microarray data. The ML models, support vector machines (SVM), and prediction analysis for microarrays (PAM) were developed using differentially expressed genes as features. The ensemble of SVM-radial and PAM predicted test samples with a precision of 81.33% (SD: 0.078). The precision of the ensemble model was significantly higher than SVM-radial (63.83%, SD: 0.081) and PAM (66.89%, SD: 0.097). The feature genes identified were enriched for biological processes such as response to stress, response to stimulus, regulation of the immune system, and metabolism of organic nitrogen compounds. The network analysis of feature genes identifiedPRF1, GZMB, IL2RB, ITGAL, andIL2RGas hub genes. Additionally, the ensemble model developed using microarray data classified the RNA-Sequencing samples with moderately high precision (72.00%, SD: 0.08). The pipeline developed in this study allows the prediction of a single microarray and RNA-Sequencing sample. In summary, this study developed robust models for clinical application and suggested ensemble learning for higher diagnostic precision in psychiatric disorders.

Research highlights

Ensemble learning of Support Vector Machines (SVM) and Prediction Analysis for Microarrays (PAM) algorithms classified schizophrenia samples with higher precision.

The pipeline developed in this analysis produced robust models with the ability to classify single microarray sample.

Cross-platform validation of ensemble model using RNA-Sequencing data resulted in high precision.

Graphical abstract

Blood based SCZ diagnosis using ensemble learning for higher precision
Efficacy and safety of bempedoic acid in women with hypercholesterolemia: Pooled analyses from phase 3 trials
Authors: Goldberg Anne C. , Banach Maciej , Catapano Alberico L. , Duell P. Barton , Leiter Lawrence A. , Hanselman Jeffrey C. , Lei Lei , Mancini G.B. John
Published: February 2023

Background and aims

Sex-specific differences in the response to lipid-lowering therapies have been reported. Here, we assessed the effect of bempedoic acid in women and men using pooled, patient-level data from four phase 3 clinical trials of bempedoic acid.

Methods

Patients were grouped into two pools: atherosclerotic cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolemia (HeFH) “on statins”, and “low-dose or no statin”. Percent changes from baseline to at least week 12 in low-density lipoprotein-cholesterol (LDL-C), non–high-density lipoprotein-cholesterol (non–HDL-C), total cholesterol (TC), apolipoprotein B (Apo B), and high-sensitivity C-reactive protein (hsCRP), as well as safety, were analyzed by statin pool and sex.

Results

Overall, 3623 patients were included (bempedoic acid, 2425; placebo, 1198). Significant reductions in lipid parameters and hsCRP were observed with bempedoic acidvs. placebo in both sexes in the ASCVD and/or HeFH on statins (n = 3009) and the low-dose or no statin (n = 614) pools (p≤0.002). Compared with men, women had significantly greater placebo-corrected reductions in LDL-C (−21.2%vs. −17.4%;p=0.044), non–HDL-C (−17.3%vs. −12.1%;p=0.003), TC (−13.8%vs. −10.5%;p=0.012), and Apo B (−16.0%vs. −11.3%;p=0.004) in the ASCVD and/or HeFH on statins pool. Women had numerically greater reductions than men in lipid parameters in the low-dose or no statin pool and hsCRP in both pools. The safety of bempedoic acid was comparable between sexes.

Conclusions

In this pooled analysis, women experienced significant improvements in levels of LDL-C and other lipid parameters with bempedoic acid.
Clinically relevant gene signatures provide independent prognostic information in older breast cancer patients
Authors: Castresana-Aguirre Miguel , Johansson Annelie , Matikas Alexios , Foukakis Theodoros , Lindström Linda S. , Tobin Nicholas P.
Published: February 2023

Purpose

Gene signatures have been shown to add prognostic information beyond that of routine clinico-pathological factors, however their utility in older breast cancer patients remains unclear. As such, the aim of this study was to determine if gene signatures can provide prognostic information that may aid treatment decisions for older breast cancer patients.

Experimental design

Research versions of the genomic grade index (GGI), 70-gene recurrence score (RS), cell cycle score (CCS), PAM50 Risk of Recurrence score - Proliferation (ROR-P), and PAM50 signatures were applied to 39 breast cancer datasets totalling 9583 patients. After filtering based on age ≥ 70 years, the presence of Estrogen Receptor (ER) and survival information availability 871 patients remained. The prognostic capacity of signatures was tested in all (n=871), ER-positive/lymph node-positive (ER+/LN+, n=335) and ER-positive/lymph node-negative (ER+/LN-, n=374) patients using Kaplan-Meier and multivariable Cox proportional hazard modeling.

Results

All gene signatures were statistically significant in Kaplan-Meier analysis of all and ER+/LN+ patients (Log-rankP< 0.001). This significance remained in multivariable analysis (Cox proportional hazards,P≤ 0.05). In ER+/LN-patients the GGI, 70-gene, CCS, ROR-P, and PAM50 signatures were significant in Kaplan-Meier analysis (Log-rankP≤ 0.05) but only the 70-gene, CCS, ROR-P, and PAM50 signatures remained so in multivariable analysis (Cox proportional hazards,P≤ 0.05).

Conclusions

In general, we found that gene signatures provide prognostic information in survival analyses of all, ER+/LN+ and ER+/LN-older (≥70 years) breast cancer patients, suggesting a potential role in aiding treatment decision in older patients.

Translational Relevance

The utility of gene expression signatures in breast cancer patients has been most clearly demonstrated in the TAILORx, RxPONDER and MINDACT randomised clinical trials. However, few older patients (≥70 years) were included in these trials meaning that signature utility in this patient group remains unclear. As such, we performed the first comprehensive study comparing the prognostic performance of multiple clinically relevant gene expression signatures in a single older breast cancer patient cohort. We show that in general gene signatures provide independent prognostic information in All, ER+/LN+ and ER+/LN-patients who are over the age of 70 years. These results support a potential role for signatures in aiding treatment decisions in older breast cancer patients and indicate that further investigation is warranted in prospective clinical study to elucidate their treatment predictive value.
Prebiotic activity of lactulose optimizes gut metabolites and prevents systemic infection in liver disease patients
Authors: Odenwald Matthew A. , Lin Huaiying , Lehmann Christopher , Dylla Nicholas P. , Ramanswamy Ramanujam , Moran Angelica , Hutchison Alan L. , Stutz Matthew R. , Cruz Mark Dela , Adler Emerald , Boissiere Jaye , Khalid Maryam , Cantoral Jackelyn , Haro Fidel , Oliveira Rita A. , Waligurski Emily , Cotter Thomas G. , Light Samuel H. , Beavis Kathleen G. , Sundararajan Anitha , Sidebottom Ashley M. , Reddy K. Gautham , Paul Sonali , Pilliai Anjana , Te Helen S. , Rinella Mary E. , Charlton Michael R. , Pamer Eric G. , Aronsohn Andrew I.
Published: February 2023

Progression of chronic liver diseases is precipitated by hepatocyte loss, inflammation and fibrosis. This process results in the loss of critical hepatic functions, increasing morbidity and the risk of infection. Medical interventions that treat complications of hepatic failure, including antibiotic administration for systemic infections, impact gut microbiome composition and metabolite production. Using a multi-omics approach on 850 fecal samples from 263 patients with acute or chronic liver disease, we demonstrate that patients hospitalized for liver disease have reduced microbiome diversity and a paucity of bioactive metabolites. We find that patients treated with the orally administered but non-absorbable disaccharide lactulose have increased densities of intestinalBifidobacteriaand reduced incidence of systemic infections and mortality.Bifidobacteriametabolize lactulose, produce high concentrations of acetate and acidify the gut lumen, which, in combination, can reduce the growth of antibiotic-resistant pathobionts such as Vancomycin-resistantEnterococcus faecium. Our studies suggest that lactulose andBifidobacteriaserve as a synbiotic to reduce rates of infection in patients with severe liver disease.
Generative Molecular Design and Experimental Validation of Selective Histamine H1 Inhibitors
Authors: McLoughlin Kevin S. , Shi Da , Mast Jeffrey E. , Bucci John , Williams John P. , Jones W. Derek , Miyao Derrick , Nam Luke , Osswald Heather L. , Zegelman Lev , Allen Jonathan , Bennion Brian J. , Paulson Amanda K. , Abagyan Ruben , Head Martha S. , Brase James M.
Published: February 2023

Generative molecular design (GMD) is an increasingly popular strategy for drug discovery, using machine learning models to propose, evaluate and optimize chemical structures against a set of target design criteria. We present the ATOM-GMD platform, a scalable multiprocessing framework to optimize many parameters simultaneously over large populations of proposed molecules. ATOM-GMD uses a junction tree variational autoencoder mapping structures to latent vectors, along with a genetic algorithm operating on latent vector elements, to search a diverse molecular space for compounds that meet the design criteria. We used the ATOM-GMD framework in a lead optimization case study to develop potent and selective histamine H1 receptor antagonists. We synthesized 103 of the top scoring compounds and measured their properties experimentally. Six of the tested compounds bind H1 withKi’s between 10 and 100 nM and are at least 100-fold selective relative to muscarinic M2 receptors, validating the effectiveness of our GMD approach.
Enhanced protein secretion in reduced genome strains ofStreptomyces lividans
Authors: Hamed M. B. , Busche T. , Simoens K. , Carpentier S. , Kormanec J. , Van Mellaert L. , Anné J. , Kalinowski J. , Bernaerts K. , Karamanou S. , Economou A.
Published: February 2023

S. lividansTK24 is a popular host for the production of small molecules and for the secretion of heterologous proteins. TK24 has a large genome with at least 29 secondary metabolite gene clusters that are non-essential for viability and undergo complex regulation. To optimize heterologous protein secretion, we previously constructed ten chassis strains that are devoid of several secondary metabolite gene clusters. Genome reduction was aimed at reducing carbon flow to secondary metabolites and pigmentation in the spent growth medium and improving colony morphology. Strains RG1.0-RG1.10 contain various deletion combinations of the blue actinorhodin cluster (act), the calcium-dependent antibiotic (cda), the undecylprodigiosin (red) and coelimycin A (cpk) clusters, the melanin cluster (mel), thematAB genes that affect mycelial aggregation and the non-essential sigma factorhrdD that controls the transcription of Act and Red regulatory proteins. Two derivative strains, RG1.5 and 1.9, showed a ∼15% reduction in growth rate, >2-fold increase in the total mass yield of their native secretome and altered abundance of several specific proteins compared with TK24. Metabolomics and RNAseq analysis revealed that genome reduction led to rapid cessation of growth due to aminoacid depletion and caused both redox and cell envelope stresses, upregulation of the Sec-pathway componentssecDFand chaperones and a cell envelope two component regulator. RG1.9 maintained elevated heterologous secretion of mRFP and mTNFα by 12-70%. An integrated model is presented linking genome reduction and enhanced secretion.
Quality in Clinical Research: An Observational Study of Randomisation Techniques in Urological and General Surgical Studies
Authors: Raison Nicholas , Giona Simone , Brunckhorst Oliver , Cohen Alexander , Muir Gordon
Published: February 2023

Objectives

To quantitatively test the quality of randomised controlled trials reported to international scientific meetings through a critical analysis of randomisation outcomes.

Design and Main Outcome Measures

All randomised controlled trials presented at international surgical and urological congresses using simple randomisation were identified. Primary analysis of randomisation technique was performed by comparing the observed and expected numbers of trials with equal numbers of participants in each arm. Sensitivity analyses compared study design, type of study and presence of external sponsorship. All abstracts were assessed according to the CONSORT for reporting randomised trials in journal and conference abstracts checklist.

Results

345 studies met the inclusion criteria. 148 studies reported simple randomisation to allocate 26,510 patients. Randomisation technique could not be identified in 104 studies. Primary and all secondary analyses demonstrated a probability of p<0.0001 that simple randomisation was used for participant allocation in all studies. Mean consort score was 9.4

Conclusions

It is extremely unlikely that simple randomisation was performed as reported in a significant proportion of the 148 RCTs in this study. These results raise concerning questions of the veracity and reliability of current medical research. There needs to be a greater awareness of the potential for methodological inaccuracy and error.